Benzene - C6H6 - PubChem

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Compound Summary for CID 241
Benzene Cite this Record

STRUCTURE VENDORS DRUG INFO PHARMACOLOGY LITERATURE PATENTS BIOACTIVITIES
PubChem CID: 241
Chemical Names: Benzene; Benzol; Benzole; Cyclohexatriene; Pyrobenzole; Benzine More...
Molecular Formula: C6H6

Molecular Weight: 78.114 g/mol
InChI Key: UHOVQNZJYSORNBUHFFFAOYSAN
Drug Information: Therapeutic Uses FDA UNII
Safety Summary: Laboratory Chemical Safety Summary LCSS
Toxic, volatile, flammable liquid hydrocarbon byproduct of coal distillation. Benzene is used as an industrial solvent in
paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone
marrow damage chronically and is carcinogenic. It was formerly used as parasiticide.
from MeSH
Benzene is a clear, colorless, highly flammable and volatile, liquid aromatic hydrocarbon with a gasolinelike odor.
Benzene is found in crude oils and as a byproduct of oilrefining processes. In industry benzene is used as a solvent, as
a chemical intermediate, and is used in the synthesis of numerous chemicals. Exposure to this substance causes
neurological symptoms and affects the bone marrow causing aplastic anemia, excessive bleeding and damage to the
immune system. Benzene is a known human carcinogen and is linked to an increased risk of developing lymphatic and
hematopoietic cancers, acute myelogenous leukemia, as well as chronic lymphocytic leukemia. NCI05
Pharmacology from NCIt
Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. Chronic benzene exposure produces
hematotoxicity, bone marrow dysplasia Displasia is a preneoplastic or precancerous change. PMID: 16183116. It is
used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system
damage acutely and is carcinogenic. It was formerly used as parasiticide.
Metabolite Description from Human Metabolome Database
PUBCHEM COMPOUND BENZENE Create Date: 20040916
https://pubchem.ncbi.nlm.nih.gov/compound/benzene#section=Top 1/149
Contents
1 2D Structure
2 3D Conformer
3 Names and Identifiers
4 Chemical and Physical Properties
5 Related Records
6 Chemical Vendors
7 Drug and Medication Information
8 Food Additives and Ingredients
9 Pharmacology and Biochemistry
10 Use and Manufacturing
11 Identification
12 Safety and Hazards
13 Toxicity
14 Literature
15 Patents
16 Biomolecular Interactions and Pathways
17 Biological Test Results
18 Classification
19 Information Sources
1 2D Structure
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from PubChem
2 3D Conformer
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Show Hydrogens Show Atoms Animate
from PubChem
3 Names and Identifiers
3.1 Computed Descriptors
3.1.1 IUPAC Name
benzene
from PubChem
3.1.2 InChI
InChI=1S/C6H6/c1246531/h16H
from PubChem
3.1.3 InChI Key
UHOVQNZJYSORNBUHFFFAOYSAN
from PubChem
3.1.4 Canonical SMILES
C1=CC=CC=C1
from PubChem
3.2 Molecular Formula

C6H6
from ILOICSC, OSHA Occupational Chemical DB, PubChem
3.3 Other Identifiers
3.3.1 CAS
71432
from CAMEO Chemicals, ChemIDplus, EPA Chemicals under the TSCA, EPA DSStox, Human Metabolome Dat
8030306
from ChemIDplus, European Chemicals Agency ECHA, OSHA Occupational Chemical DB
26181884
from ChemIDplus
71432, 1076433
from European Chemicals Agency ECHA
3.3.2 EC Number
2007537
2324432
3.3.3 ICSC Number
0015
from ILOICSC
3.3.4 RTECS Number
CY1400000
from ILOICSC, The National Institute for Occupational Safety and Health NIOSH
DE3030000
from The National Institute for Occupational Safety and Health NIOSH
3.3.5 UN Number
1114
from CAMEO Chemicals, DOT Emergency Response Guidebook, ILOICSC, NJDOH RTK Hazardous Substance
3.3.6 UNII
J64922108F
from FDA/SPL Indexing Data
3.3.7 Wikipedia
Title benzene
Description chemical compound
Wikipedia cyclohexatriene
from Wikipedia
3.4 Synonyms
3.4.1 MeSH Synonyms
1. Benzene
2. Benzol
3. Benzole
4. Cyclohexatriene
from MeSH
3.4.2 DepositorSupplied Synonyms
1. benzene 11. Mineral naphtha 21. Benzolo 31. Benzolo [Italian] 41. UN 1114
2. benzol 12. Coal naphtha 22. Fenzen 32. Benzine Obs. 42. CHEBI:16716
3. benzole 13. 71432 23. Polystream 33. Benzin Obs. 43. UNIIJ64922108F
4. Cyclohexatriene 14. Bicarburet of hydrogen 24. Nitration benzene 34. NCIC55276 44. 1,3,5cyclohexatrien
5. Pyrobenzole 15. Benzolene 25. 6Annulene 35. Caswell No. 077 45. EINECS 2007537
6. Benzine 16. Benzin 26. Benzol 90 36. Benzol diluent 46. UN1114
7. Phenyl hydride 17. [6]Annulene 27. Benzeen [Dutch] 37. Benzene, pure 47. EPA Pesticide Chem
8. Pyrobenzol 18. Motor benzol 28. Benzen [Polish] 38. CCRIS 70 48. Benzene including
9. Benzen 19. Carbon oil 29. Fenzen [Czech] 39. NSC 67315 49. AI300808
10. Phene 20. Benzeen 30. Rcra waste number U019 40. HSDB 35 50. CHEMBL277500
from PubChem
4 Chemical and Physical Properties
4.1 Computed Properties
Property Name Property Value
Molecular Weight 78.114 g/mol
Hydrogen Bond Donor Count 0
Hydrogen Bond Acceptor Count 0
Rotatable Bond Count 0
Complexity 15.5
AAADcYBgAAAAAAAAAAAAAAAAAAAAAAAAAAAwAAA
AAAAAAAABAAAAGAAAAAAACACAEAAwAIAAAACAAC
CACTVS Substructure Key Fingerprint
BCAAACAAAgAAAIiAAAAIgIICKAERCAIAAggAAIiAcAAA
AAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
Topological Polar Surface Area 0 A^2
Monoisotopic Mass 78.047 g/mol
Exact Mass 78.047 g/mol
XLogP3 2.1
Compound Is Canonicalized true
Formal Charge 0
Heavy Atom Count 6
Defined Atom Stereocenter Count 0
Undefined Atom Stereocenter Count 0
Defined Bond Stereocenter Count 0
Undefined Bond Stereocenter Count 0
Isotope Atom Count 0
CovalentlyBonded Unit Count 1
from PubChem
4.2 Experimental Properties
4.2.1 Physical Description
Benzene is a clear colorless liquid with a petroleumlike odor. Flash point less than 0F. Less dense than water and
slightly soluble in water. Hence floats on water. Vapors are heavier than air.
from CAMEO Chemicals
Liquid
from EPA Chemicals under the TSCA, Human Metabolome Database
COLOURLESS LIQUID WITH CHARACTERISTIC ODOUR.
from ILOICSC
Colorless to lightyellow liquid with an aromatic odor.

from OSHA Occupational Chemical DB
Reddishbrown, mobile liquid with an aromatic odor.

Colorless to lightyellow liquid with an aromatic odor. [Note: A solid below 42F.]
4.2.2 Color
Clear, colorless liquid

O'Neil, M.J. (ed.). The Merck Index An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of
Chemistry, 2013., p. 188
from HSDB
Orthorhombic prisms or liquid

Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 94th Edition. CRC Press LLC, Boca Raton: FL 20132014, p. 334
from HSDB
Colorless to lightyellow liquid [Note: A solid below 42 degrees F]

NIOSH. NIOSH Pocket Guide to Chemical Hazards. Department of Health & Human Services, Centers for Disease Control &
Prevention. National Institute for Occupational Safety & Health. DHHS (NIOSH) Publication No. 2010168 (2010). Available from:
http://www.cdc.gov/niosh/npg
from HSDB
4.2.3 Odor
Aromatic odor
from HSDB
Gasolinelike odor; rather pleasant aromatic odor. Odor threshold = 4.68 ppm.
Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984., p. 152
from HSDB
4.2.4 Taste
Taste threshold in water is 0.54.5 mg/l.

USEPA; Supplement to Development Doc: Haz Subset Regs Sect 311, FWPCA, (1975) EPA 440/975009
from HSDB
4.2.5 Boiling Point
176.2 F at 760 mm Hg NTP, 1992
80.08 deg C
from HSDB
80C
from ILOICSC
230 to 374F
from OSHA Chemical Sampling Information
176F
from OSHA Occupational Chemical DB, The National Institute for Occupational Safety and Health NIOSH
320428F
4.2.6 Melting Point
41.9 F NTP, 1992

5.558 deg C
from HSDB
5.5 C
from Human Metabolome Database
6C
from ILOICSC
FRZ: 42F
42F
4.2.7 Flash Point
12 F NTP, 1992
12 Deg F 11 Deg C Closed Cup

from HSDB
11.0 deg C 12.2 deg F Closed cup
SigmaAldrich; Material Safety Data Sheet for Benzene. Product Number: 12540, Version 5.2 (Revision Date 06/23/2014). Available
from, as of October 9, 2014: http://www.sigmaaldrich.com/safetycenter.html
from HSDB
11C c.c.
from ILOICSC
12F
100109F
4.2.8 Solubility
1 to 5 mg/mL at 64 F NTP, 1992

In water, 1.79X10+3 mg/L at 25 deg C

May WE et al; J Chem Ref Data 28: 1970200 (1983)
from HSDB
Miscible with alcohol, chloroform, ether, carbon disulfide, acetone, oils, carbon tetrachloride, and glacial acetic acid
from HSDB
Miscible with ethanol, ethyl ether, acetone, chloroform; coluble in carbon tetrachloride
from HSDB
1.79 mg/mL
in water, g/100ml at 25C: 0.18

from ILOICSC
0.07%
4.2.9 Density
0.879 at 68 F USCG, 1999

0.8756 g/cu cm at 20 deg C

from HSDB
water = 1: 0.88
from ILOICSC
0.88
0.890.97
4.2.10 Vapor Density
2.77 NTP, 1992 Relative to Air

2.8 Air = 1
Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997., p. 32516
from HSDB
air = 1: 2.7
from ILOICSC
4.2.11 Vapor Pressure
60 mm Hg at 59 F ; 76 mm Hg at 68 F NTP, 1992
94.8 mm Hg at 25 deg C
Daubert, T.E., R.P. Danner. Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington, D.C.: Taylor
and Francis, 1989., p. 361
from HSDB
Vapour pressure
kPa at 20C: 10
from ILOICSC
<5 mm
75 mmHg
<5 mmHg
4.2.12 LogP
log Kow = 2.13

Hansch, C., Leo, A., D. Hoekman. Exploring QSAR Hydrophobic, Electronic, and Steric Constants. Washington, DC: American
Chemical Society., 1995., p. 18
from HSDB
2.13
HANSCH,C ET AL. (1995)
2.13
from ILOICSC
4.2.13 Stability
Stable under recommended storage conditions.

from HSDB
4.2.14 AutoIgnition
1097 F USCG, 1999

928 deg F 498 deg C

National Fire Protection Association; Fire Protection Guide to Hazardous Materials. 14TH Edition, Quincy, MA 2010, p. 32518
from HSDB
498C
from ILOICSC
4.2.15 Viscosity
0.604 mPa.s at 25 deg C

from HSDB
4.2.16 Heat of Combustion
3267.6 kJ/mol liquid

from HSDB
4.2.17 Heat of Vaporization
33.83 kJ/mol at 25 deg C

from HSDB
4.2.18 Surface Tension
28.22 mN/m at 25 deg C
from HSDB
4.2.19 Ionization Potential
9.24 eV
4.2.20 Odor Threshold
4.68 PPM
U.S. Coast Guard, Department of Transportation. CHRIS Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government
Printing Office, 19845.
from HSDB
In air: 4.9 mg/cu m characteristic odor, in water: 2.0 mg/l.

USEPA; Health Advisories for 25 Organics: Benzene p.19 (1987) PB 87235578
from HSDB
distinct odor: 310 mg/cu m= 90 ppm

Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 12. 4th ed. John Wiley & Sons. New York, NY.
2001, p. 256
from HSDB
human odor perception: 3.0 mg/cu m=1 ppm

2001, p. 256
from HSDB
4.2.21 Relative Evaporation Rate
2.8 Ether = 1
AAI, Alliance of American Insurers, Handbook of Organic Industrial Solvents (1980) as cited in DHHS/ATSDR; Toxicological Profile
for Benzene (Draft) p.34 (Dec/1987)
from HSDB
4.2.22 Kovats Retention Index
Standard nonpolar 647.5, 638.32, 638.98, 645, 630, 640.2, 639, 638.6, 640.7, 645, 645, 646, 643.1,
640.5, 641.77, 641.83, 630, 644, 654, 641.72, 642, 642, 654, 654, 648, 648.9, 651.4,
640.61, 643.07, 644.46, 654, 642.7, 645.26, 646, 647.11, 642, 650, 648, 647, 645,
646.8, 648.9, 650.2, 651.1, 652.6, 657.6, 638, 649.89, 651.77, 653.93, 656.09,
658.35, 660.36, 663.6, 664.4, 666.96, 670.44, 672.02, 674.86, 672, 684.6, 629,
670.45, 654.52, 662, 663, 663, 668, 654, 649.7, 644, 677, 654.7, 660.2, 663.2, 667.4,
649.4, 656.3, 643, 678.1, 688, 653.5, 653.8, 654.2, 654.2, 654.4, 649, 647.2, 669.9,
666, 655, 655, 664, 664, 663.1, 670.7, 663, 651.3, 651.4, 655.4, 655.8, 654, 655,
661.6, 649, 653, 658, 661, 662, 664, 672, 652.1, 654.1, 656, 658.3, 681, 655, 681,
668, 675, 669, 662, 662, 664, 664, 647, 649, 651, 653, 656, 658, 653.8, 654.4, 657.1,
664, 652, 659, 670, 664, 671, 678, 642, 650, 651, 653, 654, 645.7, 648, 648.4, 650.3,
650.5, 652.6, 652.7, 654.9, 655.2, 657.2, 658.2, 659.7, 663.6, 670.7, 677.8, 646,
659.1, 647, 648, 674, 650, 654.7, 654.7, 654.8, 654.8, 654.8, 654.8, 652, 654, 654,
656, 656, 692, 660, 648, 643, 653, 657, 660, 663, 667, 668, 668, 637, 658, 662, 668,
668, 668, 668, 672, 678, 670, 657, 651, 654.1, 656, 644.9, 647.7, 647.5, 643.1, 656.1,
644.1, 639.25, 645.5, 654, 664, 652, 651.5, 638.83, 649, 640, 651.1, 649, 654, 657,
655, 648, 654, 657, 664, 657, 643, 640, 653, 651, 640, 658, 657, 663, 664, 670, 670,
649, 638, 640, 640, 660, 665, 654, 655, 655, 656, 657, 658, 659, 653, 644, 647,
648.6, 658, 663.5, 664.6, 642, 644, 643, 644, 638, 634, 644, 640.5, 665, 644, 641,
653, 669, 673, 651, 655, 660, 642, 641, 644, 670, 648, 652, 653, 665, 665, 654
663, 654, 662, 663, 648, 653.8, 654.8, 654.2, 654.8, 656.1, 660.6, 648, 659, 658, 664,
654.1, 660.1, 653.8, 654.2, 654.8, 654.8, 656.1, 654, 655.57, 658.13, 659.63, 672.74,
674.03, 685, 694.74, 664, 667, 686, 678.8, 683.3, 641.45, 641.51, 641.96, 666.03,
667.42, 669.56, 671.74, 673.5, 675.7, 677.75, 680.27, 681.27, 683.59, 685.29,
687.79, 682.5, 676, 686.4, 662, 636.6, 639.1, 641.7, 644.5, 646.6, 650, 652.5, 677.2,
675, 649.9, 681.3, 649, 675, 637.2, 641.8, 666.5, 667.4, 650, 645, 637, 641.4, 630,
650, 687, 646, 642, 651, 687, 647, 652, 653, 670, 675, 671.1, 673, 675.1, 677.2,
679.5, 681.9, 647, 650, 685.2, 685.6, 686.8, 687.4, 667, 680, 648, 650.22, 638, 638,
Semistandard nonpolar
642.9, 683, 650, 637.4, 642.2, 637.2, 642.5, 651, 652, 648, 642.5, 642.9, 647.8, 648,
648.7, 649, 641.1, 641.4, 648, 650.2, 636.8, 684, 650, 645.5, 646, 659.2, 678.8, 639,
642, 644.42, 652, 650, 636, 644, 637, 642, 650.4, 638, 660.7, 644, 649, 652, 655,
657, 660, 662, 640, 639.7, 665, 648, 637, 685, 648.5, 646.6, 653.6, 681, 634, 640,
645, 649, 645, 650, 655, 660, 680, 681, 686, 694, 631, 632, 634, 643, 645, 691, 653,
657, 642, 642, 657, 655, 661, 661, 665.5, 646, 643.7, 659.9, 655.6, 663, 686, 653,
662, 663, 671, 661, 645.3, 667, 655.1, 643, 668, 661, 674, 671.3, 654.4, 625, 640,
650.4, 663, 666, 652, 663, 638, 650, 682, 610, 622, 645, 645, 654, 635, 658, 655
936, 938, 938, 938, 936, 940, 954, 942, 943, 947, 930, 939, 938, 940, 947, 938, 926,
965, 947, 979, 979.4, 988.6, 999.5, 1007.64, 947.77, 953.66, 963.67, 971.57, 980.53,
989.54, 998.62, 953, 970, 971, 925, 955.5, 945.2, 958.2, 959.5, 964, 967.7, 992, 952,
924, 971, 957.21, 960.69, 964.88, 968.66, 972.8, 976.91, 979, 954.5, 965.7, 973.3,
Standard polar 979.3, 982.6, 969.7, 974.2, 978.8, 983.4, 992.6, 959, 955, 967, 972.6, 973.4, 985.7,
947.2, 933.4, 1000, 1005, 978, 987, 991, 970, 985, 967, 974, 981, 987, 957, 936,
938, 951, 937, 936, 938, 924, 956, 965, 975, 982, 994, 964.3, 955, 956, 957, 979,
983, 934, 951.4, 943.9, 947, 952, 959, 960, 965, 938, 932, 933, 959.5, 947, 954, 938,
930, 947, 950, 937, 937, 937, 938, 937, 937, 935, 959, 965, 948, 947.6, 946.6, 956.4
from NIST
4.3 Crystal Structures
Crystal Structures: 1 of 7
CCDC Number 298305
Crystal Structure Data DOI:10.5517/ccb0drg
Associated Article DOI:10.1107/S010876810503747X
from The Cambridge Structural Database
CCDC Number 298306
Crystal Structure Data DOI:10.5517/ccb0dsh
CCDC Number 298307
Crystal Structure Data DOI:10.5517/ccb0dtj

View All 7 Crystal Structures
4.4 Spectral Properties

MAX ABSORPTION ALCOHOL: 243 NM LOG E= 2.2, 249 NM LOG E= 2.3, 256 NM LOG E= 2.4, 261 NM LOG E=
2.2; SADTLER REF NUMBER: 6402 IR, PRISM, 1765 UV
Weast, R.C. (ed.) Handbook of Chemistry and Physics, 68th ed. Boca Raton, Florida: CRC Press Inc., 19871988., p. C146
from HSDB
Index of refraction: 1.5011 at 20 deg C/D

from HSDB
Intense mass spectral peaks: 78 m/z

Pfleger, K., H. Maurer and A. Weber. Mass Spectral and GC Data of Drugs, Poisons and their Metabolites. Parts I and II. Mass Spectra
Indexes. Weinheim, Federal Republic of Germany. 1985., p. 73
from HSDB
UV: 198 Sadtler Research Laboratories Spectral Collection

Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p.
V1: 575
from HSDB
MASS: 61115 NIST/EPA/MSDC Mass SPectral Database, 1990 version; 1790 Atlas of Mass Spectral Data, John Wiley
& Sons, New York
V1: 575
from HSDB
IR: 136 Sadtler Research Laboratories IR Grating Collection

V1: 575
from HSDB
Raman: 66 Dollish et al; Characteristic Raman Frequencies of Organic Compounds, John Wiley & Sons, New York
V1: 575
from HSDB
NMR: 3429 Sadtler Research Laboratories Spectral Collection

V1: 575
from HSDB
13C NMR: 49 Stothers, Carbon13 NMR Spectroscopy, Academic Press, New York
V1: 575
from HSDB
4.4.1 GCMS
1 of 4
NIST Number 114388
Library Main library
Total Peaks 26
m/z Top Peak 78
m/z 2nd Highest 77
m/z 3rd Highest 51
CLICK TO LOAD...
Thumbnail
from NIST
4.4.2 MSMS
1. MSMS Spectrum 6501 EIB HITACHI RMU7M Positive

2. MSMS Spectrum 6502 EIB JEOL JMSD3000 Positive
3. MSMS Spectrum 6503 EIB HP 5970 Positive
4. MSMS Spectrum 6504 CIB FINNIGANMAT 4500 Positive
4.4.3 EIMS
EIMS Spectrum 1270
4.4.4 1D NMR
1. 1D NMR Spectrum 2592 JEOL 300 MHz 1H NMR

2. 1D NMR Spectrum 3288 Varian 25.16 MHz 13C NMR
4.4.5 2D NMR
2D NMR Spectrum 1659 Bruker 600 MHz 1H13C HSQC

5 Related Records
CLICK TO LOAD...
from NCBI
5.1 Related Compounds with Annotation
CLICK TO LOAD...
from PubChem
5.2 Related Compounds
Same Connectivity 24 records
Same Parent, Connectivity 462 records
Same Parent, Exact 425 records
Mixtures, Components, and

7515 records
Neutralized Forms
Similar Compounds 989 records
Similar Conformers 9950 records
from PubChem
5.3 Substances
5.3.1 Related Substances
All 10646 records
Same 526 records
Mixture 10120 records
from PubChem
5.3.2 Substances by Category
CLICK TO LOAD...
from PubChem
5.4 Entrez Crosslinks
PubMed 29114 records
Protein Structures 21 records
Taxonomy 9 records
OMIM 20 records
Gene 993 records
from PubChem
6 Chemical Vendors
CLICK TO LOAD...
from PubChem
7 Drug and Medication Information
7.1 Therapeutic Uses

MEDICATION VET: Has been used as a disinfectant. /Former Use/
from HSDB
7.2 Drug Warning

Protected intercourse may be prudent following high exposure to benzene. As well, nursing mothers may be advised
to discontinue nursing for 5 days following high exposure.
Zenz, C., O.B. Dickerson, E.P. Horvath. Occupational Medicine. 3rd ed. St. Louis, MO., 1994, p. 712
from HSDB
7.3 Minimum/Potential Fatal Human Dose

Immediately dangerous to life and health = 500 ppm
Sullivan, J.B., Krieger G.R. (eds). Clinical Environmental Health and Toxic Exposures. Second edition. Lippincott Williams and Wilkins,
Philadelphia, Pennsylvania 1999., p. 754
from HSDB
... It has been estimated that 510 minutes of exposure to 20,000 ppm benzene in air is usually fatal.
U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Benzene p.30 PB2008
100004 (2007). Available from, as of August 12, 2014: http://www.atsdr.cdc.gov/toxprofiles/index.asp
from HSDB
Estimated oral doses from 930 g have proved fatal.

WHO; Environmental Health Criteria 150: Benzene p.46 (1993)
from HSDB
Single exposures to concentrations of 66,000 mg/cu m 20,000 ppm commercial benzene have been reported to be
fatal in man within 510 minutes. At lower levels, loss of consciousness, irregular heartbeat, dizziness, headache and
nausea are observed.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization,
International Agency for Research on Cancer, 1972PRESENT. (Multivolume work). Available at:
http://monographs.iarc.fr/ENG/Classification/index.php , p. V29 116 (1982)
from HSDB
8 Food Additives and Ingredients
8.1 Food Additive Classes
JECFA Functional Classes

Food Additives: EXTRACTION_SOLVENT
from FAO/WHO Food Additive Evaluations JECFA
8.2 Evaluations of the Joint FAO/WHO Expert Committee on Food Additives

JECFA
Chemical Name BENZENE
ADI NOT TO BE USED
Evaluation Year 1979
Report TRS 648JECFA 23/18
9 Pharmacology and Biochemistry
9.1 Pharmacology
Benzene is a clear, colorless, highly flammable and volatile, liquid aromatic hydrocarbon with a gasolinelike odor.
Benzene is found in crude oils and as a byproduct of oilrefining processes. In industry benzene is used as a solvent,
as a chemical intermediate, and is used in the synthesis of numerous chemicals. Exposure to this substance causes
neurological symptoms and affects the bone marrow causing aplastic anemia, excessive bleeding and damage to the
immune system. Benzene is a known human carcinogen and is linked to an increased risk of developing lymphatic and
hematopoietic cancers, acute myelogenous leukemia, as well as chronic lymphocytic leukemia. NCI05
from NCIt
9.2 Absorption, Distribution and Excretion

Benzene is readily absorbed via lung, & about 4050% is retained. ... It is taken up preferentially by fatty & nervous
tissues, & about 3050% ... is excreted unchanged via lung; a 3phase excretion pattern is seen at ... /approx/ 0.71.7
hr, 34 hr, & 2030 hr.
from HSDB
When benzene was placed on skin under closed cup it was absorbed at rate of 0.4 mg/sq cm/hr Hanke et al 1961 ...
from HSDB
Mice treated SC with 2 mL 3Hlabeled benzene/kg contained irreversibly bound radioactivity with decreasing
binding magnitude in the following organs: liver, brain, kidney, spleen, fat. Mice treated with 2 daily SC doses of 0.5
mL 3Hbenzene/kg for 110 days showed a radioactivity binding with liver & bone marrow residues which increased
with treatment duration, except in the case of binding to bone marrow which decreased after day 6. Abstract: PubMed
Snyder R et al; Res Commun Chem Pathol Pharmacol 20 (1): 1914 (1978)
from HSDB
When administered to mice subcutaneously, 72% of dose is recovered in expired air. Abstract: PubMed
Andrews LS et al; Biochem Pharmacol 26: 293 (1977)
from HSDB
Rats were exposed to 500 ppm benzene for 30 min to eight hr. Benzene concentrations reached steady state within
four hr in blood steadystate concn= 11.5 ug/g, six hr in fat concn= 164.4 ug/g, and two hr in bone marrow
concn= 37.0 ug/g. Lesser concn were detected in the kidney, lung, liver, brain, and spleen. Abstract: PubMed
Rickert DE et al; Toxicol Appl Pharmacol 49: 41723 (1979)
from HSDB
Benzene is absorbed from the gastrointestinal tract when ingested.

Goodman LS, Gilmann A; The Pharm Basis of Therapeutics p.936 (1970)
from HSDB
Benzene crosses the human placenta, & levels in cord blood are similar to those in maternal blood. ... The most
frequent route by which humans are exposed to benzene is via inhalation. Toxic effects in humans have been
attributed to combined exposure by both respiration & through the skin ... it is eliminated unchanged in expired air ...
in men & women exposed to 5262 ppM 166198 mg/cu m benzene for 4 hr, a mean of 46.9% was taken up, 30.2%
was retained & the remaining 16.8% excreted as unchanged benzene in expired air. ... When humans were exposed to
100 ppM 300 mg/cu m benzene, it was detected in expired air 24 hr later, suggesting that it is possible to back
extrapolate to the benzene concentration in the inspired air.
from HSDB
The solubility characteristics of benzene are such that it is easily taken up by the stratum corneum. Once in the
stratum corneum, it does not meet many restraining forces to impede its movement and diffuses easily. The
permeability constant for benzene, as determined in vitro, is higher than that of many other small molecules,
particularly those having one or more polar groups. ... Even though these uncertainties exist, and more data are
needed to support the ... conclusion that there is good overall agreement between in vitro and in vivo data. ... An
adult working in ambient air containing 10 ppm of benzene, with 100 cm of glaborous skin in contact with gasoline
containing 5% benzene, and his entire skin 2 sq m in contact with ambient air, will absorb in an hr, 7.5 ul of benzene
from inhalation, 7.0 ul from contact with gasoline, and 1.5 ul from body exposure to ambient air. Since ... in vitro
techniques measure the penetration of benzene through strongly hydrated stratum corneum, the calculated flux may
be higher than under some in vivo conditions. Nevertheless, it seems that unless good hygiene is maintained and care
is taken to prevent lengthy exposure to solvents containing benzene, significant amounts of benzene may enter the
body through the skin.
Blank IH, McAuliffe DJ; J Investigat Dermatol 85: 5226 (1985)
from HSDB
Subjects who inhaled concentrations of 340 mg/cu m 106 ppm benzene in air for 5 hr excreted 29% as phenol, 3%
as catechol and 1% as hydroquinone in the urine, mostly as ethereal sulfates. Most of the phenol and catechol was
excreted within 24 hr, and the hydroquinone within 48 hr.
from HSDB
In men and women exposed to 5262 ppm 166198 mg/cu m benzene for 4 hr, a mean of 46.9% was taken up,
30.2% was retained and the remaining 16.8% excreted as unchanged benzene in expired air.
from HSDB
In animals, expired air is the main route of elimination of unmetabolized benzene, while urine is the major route of
excretion of benzene metabolites with very little fecal excretion.
WHO; Environmental Health Criteria 150: p.54 (1993)
from HSDB
In a series of experiments conducted in a singlefamily residence from June 11 to 13, 1991, exposure to benzene
through contaminated residential water was monitored. The residential water was contaminated with benzene and
other hydrocarbons in 1986. Periodic testing conducted from 1986 to 1991 showed benzene concentrations ranging
from 33 to 673 ug/L ppb. The experiment involved an individual taking a 20minute shower with the bathroom door
closed, followed by 5 minutes for drying and dressing; then the bathroom door was opened and this individual was
allowed to leave the house. Integrated 60 and 240minute wholeair samples were collected from the bathroom, an
adjacent bedroom, living room, and in ambient air. Glass, gastight syringe grab samples were simultaneously
collected from the shower, bathroom, bedroom, and living room at 0, 10, 18, 20, 25, 25.5, and 30 minutes. Two
members of the monitoring team were measured for 6 hours using personal Tenax gas GC monitors. For the first 30
minutes of each experiment, one member was based in the bathroom and the other in the living room. Benzene
concentrations in the shower head ranged from 185 to 367 ug/L ppb, while drain level samples ranged from below
the detectable limit 0.6 ug/L or ppb to 198 ug/L ppb. Analysis of the syringe samples suggested a pulse of benzene
moving from the shower stall to the rest of the house over approximately 60 minutes. Peak levels of benzene
measured 7581,670 ug/cu m 235518 ppb in the shower stall at 1820 minutes, 366498 ug/cu m 113154 ppb in
the bathroom at 1025 minutes, 81146 ug/cu m 2545 ppb in the bedroom at 25.530 minutes, and 40 62 ug/cu m
1219 ppb in the living room at 3670 minutes. The individual who took the 20minute shower had estimated
inhalation doses of 79.6, 105, and 103 ug mean=95.9 ug for the 3 consecutive sampling days. These doses were
estimated by taking the products of the concentration of benzene in water, the minute ventilation rate, the duration
of exposure, and a 70% benzene absorption factor. This was 2.14.9 times higher than corresponding 20minute
bathroom exposures. Adding the average dose absorbed in the bathroom during the 5.5 minutes following the
shower using the overall 2025 minutes mean syringe level of 318 ug/cu m [99 ppb] gave a total average shower
related inhalation dose of 113 ug. An average dermal dose of 168 ug was estimated for the 20minute shower by
multiplying the average concentration of benzene in water by the surface area of the male volunteer, an exposure
factor of 75% body surface area exposed, a dermal permeability constant for benzene of 0.11 cm/hour, an exposure
duration of 0.33 hours, and a unit conversion factor of 11/1,000 cm sq . The total benzene dose resulting from the
shower was estimated to be approximately 281 ug 40% via inhalation and 60% via dermal, suggesting a higher
potential exposure to benzene via dermal contact from the water than through vaporization and inhalation. This
exposure was 23.5 times higher than the mean 6hour inhalation dose received by the sampling members.
U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Benzene p.156
PB2008100004 (2007). Available from, as of August 12, 2014: http://www.atsdr.cdc.gov/toxprofiles/index.asp
from HSDB
In SpragueDawley rats administered a single dose of 0.15, 1.5, 15, 150, or 500 mg/kg of 14Cbenzene by gavage,
benzene was rapidly absorbed and distributed to various organs and tissues within 1 hr of administration. One hour
after rats were dosed with 0.15 or 1.5 mg/kg of benzene, tissue distribution of benzene was highest in liver and
kidney, intermediate in blood, and lowest in the Zymbal gland, nasal cavity tissue, and mammary gland. At higher
doses, beginning with 15 mg/kg, benzene disproportionately increased in the mammary glands and bone marrow.
Bone marrow and adipose tissue proved to be depots of benzene at the higher dose levels. The highest tissue
concentrations of benzene's metabolite hydroquinone 1 hr after administration of 15 mg/kg of benzene were in the
liver, kidney, and blood, while the highest concentrations of the metabolite phenol were in the oral cavity, nasal cavity,
and kidney. The major tissue sites of benzene's conjugated metabolites were blood, bone marrow, oral cavity, kidney,
and liver for phenyl sulfate and hydroquinone glucuronide; muconic acid was also found in these sites. Additionally,
the Zymbal gland and nasal cavity were depots for phenyl glucuronide, another conjugated metabolite of benzene.
The Zymbal gland is a specialized sebaceous gland and a site for benzeneinduced tumors. Therefore, it is reasonable
to expect that lipophilic chemicals like benzene would partition readily into this gland. However, benzene did not
accumulate in the Zymbal gland; within 24 hr after administration, radiolabel derived from 14Cbenzene in the Zymbal
gland constituted less than 0.0001% of the administered dose.
from HSDB
Monkeys were dosed intraperitoneally with 5500 mg/kg radiolabeled benzene, and urinary metabolites were
examined. The proportion of radioactivity excreted in the urine decreased with increasing dose, whereas the dose
increased, more benzene was exhaled unchanged. This indicated saturation of benzene metabolism at higher doses.
Phenyl sulfate was the major urinary metabolite. Hydroquinone conjugates and muconic acid in the urine decreased
as the dose increased.
from HSDB
9.3 Metabolism/Metabolites
The major metabolitesof benzene metabolism are phenol, hydroquinone, and catechol. These metabolites are
interactive and can affect the rate of each other's metabolism because they are substrates for the P450 enzyme
system. The route of exposure has little effect on the subsequent metabolism of benzene to hemotoxic metabolites.
from HSDB
Metabolic products in rat ... are phenol, hydroquinone, catechol, hydroxyhydroquinone, & phenylmercapturic acid.
Conjugated phenols have been reported ... except for a small amt of free phenol, all the phenolic metabolites were
excreted in conjugated form. When 3Hbenzene was admin to mice, 3H2O was also recovered from urine.
National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 688
from HSDB
Yields NacetylSphenylcysteine in rat. Yields benzyl alcohol in guinea pigs. ... Yields cis1,2dihydro1,2
dihydroxybenzene in pseudomonas. Phenol in pseudomonas & achromobacter. Yields cis,cismuconic acid in rabbit.
/From table/
Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976., p. B4
from HSDB
In the rabbit, the major hydroxylation product of benzene was phenol, which along with some catechol and
hydroquinone, was found in the urine conjugated with ethereal sulfate or glucuronic acid.
USEPA; Ambient Water Quality Criteria: Benzene p.C11 (1980) EPA 440/580018
from HSDB
Unconjugated phenol has been found in mouse and rat urine after benzene administration.
from HSDB
The formation of benzene oxide, an epoxide of benzene is involved in the metabolism of benzene. This highly
unstable intermediate rearranges nonenzymatically to form phenol. This step accounts for the occurrence of phenol
as the major metabolite of benzene in urine. Catechol formation is thought to result from the hydration of benzene
oxide by the enzyme epoxide hydratase followed by oxidation to catechol. It appears that catechol and phenol are
formed by two distinctly different metabolic pathways. Hydroquinone is thought to result from a second passage of
phenol through the mixed function oxidases.
Jerina D, Daly JW; Science 185: 573 (1974) as cited in USEPA; Ambient Water Quality Criteria: Benzene p.C12 (1980) EPA 440/5
80018
from HSDB
The metabolism of benzene in vitro can be altered by the use of enzyme inducers administered to animals prior to
sacrifice or by the addition of inhibitors to the mixtures. Benzene, phenobarbital, 3methylcholanthrene and dimethyl
sulfoxide are all microsomal stimulants for the metabolism of benzene. Benzene metabolism in vitro can be inhibited
by carbon monoxide, aniline, metyrapone, SKF525A /proadifen/, aminopyrine, cytochrome c, aminotriazole, or
toluene.
from HSDB
Benzene, when administered sc at 880 mg/kg twice daily for 3 days, decreased erythropoiesis much more markedly in
DBA/2 mice than in C57BL/6 mice. Total urinary benzene metabolites and the % of the dose excreted in the urine
were the same in both strains. Although the metabolic profile differed between the two strains, it was very similar
when equitoxic doses of benzene were administered. The levels of both free and covalently bound benzene were
higher in all organs of the DBA/2 mice. Phenol, hydroquinone, resorcinol, and catechol had no effect on erythopoiesis.
Snyder R et al; Adv Exp Biol 136A: 24556 (1982)
from HSDB
The urinary metabolites isolated by DEAE Sephadex A24 anionexchange chromatography from mice treated with
radiolabeled benzene included phenol as the major component, as well as catechol, hydroquinone, and
phenylmercapturic acid. The phenolic metabolites were excreted primarily as glucronides with the exception of a small
amount of free phenol.
Longacre SL et al; Adv Exp Med Biol 136A: 30717 (1982)
from HSDB
Benzene reduced the incorporation of 59Fe into red cells by 75% at the higher dose when administered at 440 or
880 mg/kg to mice pretreated with 59Fe 48 hr earlier. However, when toluene was administered simultaneously with
benzene in a ratio of 2:1, the depression of 59Fe uptake was prevented. Toluene reduced the appearance of benzene
metabolites to 45% of controls at the higher dose and 30% at the lower dose. Thus toluene appears to inhibit
benzene metabolism and by so doing, alleviates its toxicity.
Snyder R et al; Adv Mod Environ Toxicol 4: 12336 (1983)
from HSDB
A sensitive high performance liquid chromatography method is described which separates urinary metabolites from
benzenetreated male CD1 mice. Phenol, trans, transmuconic acid and quino in the 48 hr urine, accounted,
respectively for 12.822.8, 1.84.7 and 1.53.7% of the orally administered single dose of benzene 880, 440, and 220
mg/kg body wt. Catechol occurred in trace amounts. Trans, transmuconic acid was identified and was unique to
benzene as none was detected in urine of mice dosed orally with phenol, catechol, or quinol. The potential existence
of a toxic metabolite in the form of an aldehyde precursor of muconic acid in vivo is discussed. Abstract: PubMed
Gadel K et al; Xenobiotica 15: 21120 (1985)
from HSDB
In humans, phenol sulfate is the major metabolite of benzene until 400 mg/l levels are reached in the urine. Beyond
than level, glucuronide conjugates are also present in the urine.
from HSDB
Male Wistar rats were tested to determine the effect of enzymes with different kinetic characteristics on the
metabolism of benzene, in vitro. Kinetic analysis of the enzymes in the liver of rats fed a normal diet revealed the
presence of two benzene hydroxylases with low Michaelis constant values of 0.01 millimolar and 0.07 millimolar,
respectively. After 1 day of food deprivation, the isozyme with a constant equal to 0.01 millimolar disappeared while
the activity of the second isozyme increased. Following the administration of phenobarbital there was evidence of a
third benzene metabolizing enzyme in the liver of the animals exposed to benzene in concentrations ranging from
0.0055 to 6.25 millimolar, in vitro; the value of the Michaelis constant for this enzyme was equal to 4.5 millimolar and
was not evident in control animals. Treatment with phenobarbital failed to affect the activity of the other low
Michaelis constants of benzene hydroxylases identified in the liver of normal rats. Treatment with ethanol resulted in
significant increase in the activity of both normally occurring benzene hydroxylases in the normal liver.
Nakajima T et al; Biochemical Pharmacol 36 (17): 2799804 (1987)
from HSDB
Mitoplasts mitochondria with the outer membrane removed from the bone marrow of rabbits were incubated
sequentially with 3Hlabeled deoxyguanosine triphosphate and 14Clabeled benzene to study the DNA adducts
formed from benzene metabolites in mitochondria. Following isolation and isopycnic density gradient centrifugation
in CsCl, the doubly labeled DNA was hydrolyzed to deoxynucleosides and separated on a Sephadex LH 20 column. At
least seven deoxyguanosine adducts and one deoxyadenine adduct were present. Abstract: PubMed
Snyder R et al; Arch Toxicol 60 (13): 614 (1987)
from HSDB
The major benzene metabolite produced by the liver P450 enzyme system is phenol. Phenol is than further oxidized
by the P450 enzyme system to hydroquinone. Both hydroquonone and phenol can be conjugated in the liverto
nontoxic products, or can diffuse into bone marrow. Once in bone marrow, phenol and hydroquinone can be acted
upon by the myeloperoxidasedependent enzyme system, which metabolizes hydroquinone to reactive
benzoquinone, stimulated by the presence of phenol... Benzoquinone has been shown to be both myelotoxic and
clastogenic.
from HSDB
... Literature identifies the following metabolites after incubation of benzene with mouse liver microsomes: phenol,
hydroquinone, trans,transmuconaldehyde, 6oxotrans,trans2,4hexadienoic acid, 6hydroxytrans,trans,24,
hexadienal, and 6hydroxytrans,trans2,4hexadienoic acid. Betahydroxymuconaldehyde, a new metabolite, was also
identified.
from HSDB
Data produced in vitro by mouse and rat liver microsomes ... indicate species differences in benzene metabolism.
Quantitation of metabolites from the microsomal metabolism of benzene indicated that after 45 min, mouse liver
microsomes from male B6C3F1 mice had converted 20% of the benzene to phenol, 31% to hydroquinone, and 2% to
catechol. In contrast, rat liver microsomes from male Fischer 344 rats converted 23% to phenol, 8% to hydroquinone,
and 0.5% to catechol. Mouse liver microsomes continued to produce hydroquinone and catechol for 90 min, whereas
rat liver microsomes had ceased production of these metabolites by 90 min. Muconic acid production by mouse liver
microsomes was <0.04 and <0.2% from phenol and benzene, respectively, after 90 min.
from HSDB
Subjects who inhaled concentrations of 340 mg/cu m 106 ppm benzene in air for 5 hr excreted 29% as phenol, 3%
as catechol and 1% as hydroquinone in the urine, mostly as ethereal sulfates.
from HSDB
Chronic exposure to benzene has been correlated with increased oxidative stress and leukemia. Oncogene activation,
including cMyb activation, is one of the earliest steps leading to the formation of leukemic cells, however the
molecular mechanisms involved in these events are poorly understood. Given that oxidative stress can alter the
activity and fate of cell signaling pathways we hypothesize that the bioactivation of benzene leads to the formation of
reactive oxygen species ROS, which if not detoxified can alter the cMyb signaling pathway. Using chicken
erythroblast HD3 cells we have shown that exposure to the benzene metabolites catechol, benzoquinone, and
hydroquinone leads to increased cMyb activity, increased phosphorylation of cMyb and increased production of
ROS supporting our hypothesis. Activation of the aryl hydrocarbon receptor AhR by environmental contaminants has
also been associated with carcinogenesis and mice lacking this receptor are resistant to benzeneinitiated
hematotoxicity. Using wild type and AhR deficient cells we are investigating the role of this receptor in benzene
initiated alterations in the cMyb signaling pathway. We have found that both wild type and AhR deficient cells are
sensitive to catechol and hydroquinoneinitiated increases in cMyb activity while both cell types are resistant to
benzeneinitiated alterations leaving the role of the AhR still undetermined. Interestingly, protein expression of cMyb
is increased after catechol exposure in AhR deficient cells while decreased in wildtype cells. Abstract: PubMed
Wan J et al; Chem Biol Interact. 153154:1718 (2005)
from HSDB
Enzymes involved in benzene metabolism are likely genetic determinants of benzeneinduced toxicity. Polymorphisms
in human microsomal epoxide hydrolase mEH are associated with an increased risk of developing leukemia,
specifically those associated with benzene. This study was designed to investigate the importance of mEH in benzene
induced toxicity. Male and female mEHdeficient mEH/ mice and background mice 129/Sv were exposed to
inhaled benzene 0, 10, 50, or 100 ppm 5 days/week, 6 hr/day, for a twoweek duration. Total white blood cell counts
and bone marrow cell counts were used to assess hematotoxicity and myelotoxicity. Micronucleated peripheral blood
cells were counted to assess genotoxicity, and the p21 mRNA level in bone marrow cells was used as a determinant of
the p53regulated DNA damage response. Male mEH/ mice did not have any significant hematotoxicity or
myelotoxicity at the highest benzene exposure compared to the male 129/Sv mice. Significant hematotoxicity or
myelotoxicity did not occur in the female mEH/ or 129/Sv mice. Male mEH/ mice were also unresponsive to
benzeneinduced genotoxicity compared to a significant induction in the male 129/Sv mice. The female mEH/ and
129/Sv mice were virtually unresponsive to benzeneinduced genotoxicity. While p21 mRNA expression was highly
induced in male 129/Sv mice after exposure to 100ppm benzene, no significant alteration was observed in male
mEH/ mice. Likewise, p21 mRNA expression in female mEH/ mice was not significantly induced upon benzene
exposure whereas a significant induction was observed in female 129/Sv mice. Thus mEH appears to be critical in
benzeneinduced toxicity in male, but not female, mice. Abstract: PubMed
Bauer AK et al; Toxicol Sci. 2003 Apr;72(2):2019 (2003)
from HSDB
Benzene is an occupational toxicant and an environmental pollutant that potentially causes hematotoxicity and
leukemia in exposed populations. Epidemiological studies suggest an association between an increased incidence of
childhood leukemia and benzene exposure during the early stages of pregnancy. However, experimental evidence
supporting the association is lacking at the present time. It is believed that benzene and its metabolites target
hematopoietic stem cells HSCs to cause toxicity and cancer in the hematopoietic system. In the current study, /the
authors/ compared the effects of hydroquinone HQ, a major metabolite of benzene in humans and animals, on
mouse embryonic yolk sac hematopoietic stem cells YSHSCs and adult bone marrow hematopoietic stem cells BM
HSCs. YSHSCs and BMHSCs were isolated and enriched, and were exposed to HQ at increasing concentrations. HQ
reduced the proliferation and the differentiation and colony formation, but increased the apoptosis of both YSHSCs
and BMHSCs. However, the cytotoxic and apoptotic effects of HQ were more apparent and reduction of colony
formation by HQ was more severe in YSHSCs than in BMHSCs. Differences in gene expression profiles were
observed in HQtreated YSHSCs and BMHSCs. Cyp4f18 was induced by HQ both in YSHSCs and BMHSCs, whereas
DNAPKcs was induced in BMHSCs only. The results revealed differential effects of benzene metabolites on
embryonic and adult HSCs. The study established an experimental system for comparison of the hematopoietic
toxicity and leukemogenicity of benzene and metabolites during mouse embryonic development and adulthood.[Zhu
J et al; PLoS One. 2013 Aug 5;88:e71153. doi: 10.1371/journal.pone.0071153. Print 2013.] Full text: PMC3734044
Abstract: PubMed
from HSDB
In higher plants, benzene administered in aqueous solution or as vapor is translocated and metabolized. The
proposed sequence of benzene metabolism in plants is benzene /to/ phenol /to/ pyrocatechol /to/ obenzoquinone
/to/ muconic acid.
2001, p. 264
from HSDB
The principal hydroxy metabolites of benzene, hydroquinone, catechol and phenol were assayed in tests for mitotic
segregation induction in Aspergillus nidulans diploid strain 19. Hydroquinone was the most effective chemical,
increasing the frequency of mitotic segregants up to 10 fold at 13 mM. Catechol was similarly active at 1020 mM
and phenol was weakly positive at 15 mM. Genetic characterization of induced abnormal segregating colonies by
replating and complementary assays with haploid strain 35 suggest that gross chromosomal aberrations, instead of
numerical abnormalities, are the primary genetic damages induced by hydroxybenzenes in Aspergillus. The protecting
activity exerted by Lcysteine against equimolar concentrations of hydroquinone supports a free radical mechanism
for hydroxy metabolite genotoxicity in Aspergillus nidulans. Abstract: PubMed
Crebelli R et al; Mutagenesis 2 (3): 2358 (1987)
from HSDB
Environmental exposure to benzene results in both myelotoxicity and immunotoxicity. Although benzene induced
immunotoxicity has been well documented, no studies to date have addressed the possibility that benzene toxicity is
due in part to altered differentiation of marrow lymphoid cells. The effect of acute exposure to the benzene
metabolite, hydroquinone, on murine bone marrow Blymphopoiesis was investigated. Bone marrow cell suspensions
from B6C3F1 C57BL/6J x C3H/HeJ mice were depleted of mature surface IgM+ B cells and cultured for 0, 24, 48, or
72 hr and production of newly formed B cells was assayed both by mature surface expression and colony formation in
soft agar cultures. One hr exposure of bone marrow cells to hydroquinone before culture reduced the number of
mature surface cells generated in liquid cultures. Small preB cells cytoplasmic mu heavy chain+, sIgM were
numerically elevated as compared with control cultures. Hydroquinone exposure also decreased the number of
adherent cells found in cultures of bone marrow cells. These results suggest that shortterm exposure to
hydroquinone, an oxidative metabolite of benzene, may in some way block the final maturation stages of B cell
differentiation. This apparent differentiation block resulted in reduced numbers of B cells generated in culture and a
corresponding accumulation of preB cells. Reduction of adherent cells in treated cultures may also suggest that
toxicity to regulatory cells for the B lineage may be in part responsible for this aspect of hydroquinone myelotoxicity.
Abstract: PubMed
King AG et al; Mol Pharmacol 32 (6): 80712 (1987)
from HSDB
... Benzene hydroxylation was stimulated when rats were pretreated with phenobarbital and then exposed to 1,000
ppm of benzene vapor for 8 hr/day for 2 wk.
Ikeda M, Ohtsuji H; Toxicol Appl Pharmacol 20: 3043 (1971)
from HSDB
Benzene and its five metabolites, muconic acid, hydroquinone, catechol, pbenzoquinone and benzenetriol, have been
shown to produce DNA damage in hman lymphocytes.
from HSDB
9.4 Biological HalfLife

The excretion of unchanged benzene from the lung of rats was reported to be biphasic, suggesting a two
compartment model for distribution and a halflife of 0.7 hr. This agreed with experimental halflife values for various
tissues that ranged from 0.4 to 1.6 hr.
Rickert DE et al; Toxicol Appl Pharmacol 49: 417 (1979) as cited in USEPA; Ambient Water Quality Criteria: Benzene p.C11 (1980)
EPA 440/580018
from HSDB
... The halftime of benzene in /high lipid content/ tissues is approximately 24 hours.
Zenz, C., O.B. Dickerson, E.P. Horvath. Occupational Medicine. 3rd ed. St. Louis, MO., 1994, p. 146
from HSDB
9.5 Mechanism of Action

Covalent interaction of a benzene metabolite with dna was shown in vivo, but no information was given about the
chem nature of this metabolite. A likely intermediate in benzene metabolism is benzene oxide. In neutral aq media it
rearranges only slowly to the phenol so that its lifetime could be long enough for diffusion from the site of activation
to the dna. Alternatively, the metabolic appearance of polyhydroxy derivatives suggests the formation of a phenol
epoxide, so that the reactive molecule could be a secondary metabolite. Abstract: PubMed
Lutz WK, Schlatter C; Chem Biol Interact 18 (2): 2416 (1977)
from HSDB
The available evidence supports the concept that benzene toxicity is caused by one or more metabolites of benzene.
... Benzene metabolites containing 2 or 3 hydroxyl groups inhibited mitosis. Toluene, which inhibits benzene
metabolism, protected animals against benzeneinduced myelotoxicity. Benzene toxicity could be correlated with the
appearance of benzene metabolites in bone marrow. Although it is clear that benzene can be metabolized in bone
marrow, the observation that partial hepatectomy protects against benzene toxicity suggests that a metabolite
formed in liver is essential for benzene toxicity.
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... Importance of polyhydroxylated derivatives of benzene & their semiquinones. ... /It has been/ shown that
hydroquinone inhibits rat brain microtubule polymerization; that hydroquinone & parabenzoquinone are the most
potent inhibitors of T & Blymphocyte function, as measured in mouse spleen cells in culture; that hydroquinone
inhibits lectinstimulated lymphocyte agglutination in rat spleen prepn in vitro; & that parabenzoquinone is the
metabolite most likely to be responsible for suppression of lymphocyte transformation & microtubule assembly in rat
spleen cells in culture. However, admin of these cmpd to animals does not produce the typical picture of benzene
toxicity ... admin /of/ major metabolites of benzene to mice ... failed to ... decr ... red blood cell production, using the
59Fe uptake technique ... /it's been/ suggested that ringopening products may play a role in benzene toxicity. ... In
mice benzene treatment suppressed subsequent colony forming unitC formation from bonemarrow cells in vitro.
Treating the animals with phenol, hydroquinone or benzene dihydrodiol failed to suppress colony forming unitC.
Thus, the toxic metabolites of benzene have yet to be identified.
from HSDB
... Radioactivity /has been demonstrated/ in a nucleic acid fraction from rat liver following admin of either 3h or
14Clabelled benzene. It has been shown that benzene binds covalently to protein in liver, bone marrow, kidney,
lung, spleen, blood, & muscle. Less covalent binding was observed to the protein of bone marrow, blood, & spleen of
C57Bl/6 mice, which are more resistant to the benzeneinduced effects on red cell production, than to that of
sensitive DBA/2 mice. ... Covalent binding of benzene to protein in perfused bonemarrow prepn /has been
demonstrated/. ... A metabolite of phenol binds to liver protein more efficiently than does benzene oxide, & they have
electrophoretically separated hepatic proteins to which benzene preferentially binds. ... Covalent binding to
mitochondria is a prominent feature of benzene metabolism. ... There is relatively more radioactivity in a nucleic acid
rich fraction of a benzene metabolite isolated from mouse bonemarrow cells than in a similar fraction from liver.
from HSDB
Evidence indicates that benzene must be metabolically activated in order to exert its characteristic toxicity on bone
marrow. Some of the hydroxylated benzene metabolites, phenol, catechol, hydroquinone, resorcinol & some
trihydroxylated derivatives in urine of rabbits are suggested to be the toxic metabolites.
Snyder R et al; Biological Reactive Intermediates II, Part A, Plenum Publishing Corp 245 (1982)
from HSDB
The mechanism of benzene oxygenation in liver microsomes & in reconstituted enzyme systems from rabbit liver was
investigated. The results indicate that the microsomal cytochrome P450 dependent oxidation of benzene is mediated
by hydroxyl radicals formed in a modified HaberWeiss reaction between hydrogen peroxide & superoxide anions &
suggest that any cellular superoxidegenerating system may be sufficient for the metabolic activation of benzene &
structurally related compounds.
Johansson I, IngelmanSundberg M; J Bio Chem 258 (12): 73116 (1983)
from HSDB
Animal expt show that benzene sensitizes the myocardium to epinephrine, so that the endogenous hormone may
precipitate sudden & fatal ventricular fibrillation.
Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p.
III398
from HSDB
The protective effects of pyridine and xylene against benzene, benzoapyrene, or cyclophosphamide clastogenicity
were studied in mice. SwissICR mice were treated orally with 220 to 880 mg/kg benzene, 150 mg/kg benzoapyrene,
or intraperitoneally with 50 mg/kg cyclophosphamide with or without 0 to 500 mg/kg pyridine or xylene. The mice
were killed 24 to 72 hours later and the femurs were removed. The bone marrow was isolated and assayed for
micronuclei. Xylene inhibited the induction of micronuclei of benzene only when given at an equimolar dose or
greater. No delay in the peak micronuclei response was seen. Pyridine at 60 mg/kg completely blocked the induction
of micronuclei by 880 mg/kg benzene of 24 hours. Pyridine at 25 mg/kg completely blocked the clastogenic effect of
440 mg/kg benzene at 36 to 76 hours and partially blocked micronuclei induction at 24 hours. The clastogenicity of
benzoapyrene was inhibited by pyridine only at doses of 100 mg/kg or more. Pyridine showed no protective effect
against micronuclei induction by cyclophosphamide at any concn; micronuclei formation was enhanced by 60 to 260
mg/kg pyridine. Since the results suggested that the biological activation of benzene was due to different cytochrome
p450 isozymes than the ones activating benzoapyrene or cyclophosphamide, DBA/2 mice aryl hydrocarbon
hydrolase noninducible and C57B1/6 mice with or without pretreatment with methylcholanthrene were dosed once
or three times with benzene and the effects on bone marrow micronuclei were examined as before. Micronuclei
formation was greater in DBA/2 mice. The effect was potentiated by methylcholanthrene. The cytochrome p450
isozyme involved in activating benzene is one of the enzymes induced by methylcholanthrene, independent of the
high affinity aryl hydrocarbon hydrolase receptor. Abstract: PubMed
Harper BL, Legator MS; Mutat Res 179 (1): 2331 (1987)
from HSDB
Benzene is a widespread volatile compound and an environmental contaminant. Since it causes important toxic effects
in workers exposed to low levels, longterm exposure to this compound has been extensively studied. Leukemia,
blood disorders, bone marrow depression, and some types of cancer are directly related to benzeneinitiated toxicity.
Bioactivation of benzene can lead to the formation of hazardous metabolites such as phenol, hydroquinone, and
catechol. Catechol forms semiquinones and reactive quinones that are presumed to play an important role in the
generation of reactive oxygen species ROS. ROS formation can directly induce single and double strand breaks in the
DNA, oxidized nucleotides, and hyperrecombination, and consequently produces deleterious genetic changes. In this
review, we have addressed the cytotoxic effects of benzene and its main metabolite, catechol, focusing on the
oxidative pathway and further DNA damage. Abstract: PubMed
Barreto G et al; Environ Mol Mutagen. 50 (9): 77180 (2009)
from HSDB
Chronic occupational exposure to benzene has been correlated with aplastic aneamia and acute myelogenous
leukemia, however mechanisms behind benzene toxicity remain unknown. Interestingly, benzeneinitiated
hematotoxicity is absent in mice lacking the aryl hydrocarbon receptor AhR suggesting an imperative role for this
receptor in benzene toxicities. This study investigated two potential roles for the AhR in benzene toxicity using hepa
1c1c7 wild type and AhR deficient cells. Considering that many toxic effects of AhR ligands are dependent on AhR
activation, our first objective was to determine if benzene, hydroquinone HQ or benzoquinone BQ could activate
the AhR. Secondly, because the AhR regulates a number of enzymes involved in oxidative stress pathways, we sought
to determine if the AhR had a role in HQ and BQ induced production of reactive oxygen species ROS. Dual luciferase
assays measuring dioxin response element DRE activation showed no significant change in DRE activity after
exposure to benzene, HQ or BQ for 24h. Immunofluorescence staining showed cytosolic localization of the AhR after
2h incubations with benzene, HQ or BQ. Western blot analysis of cells exposed to benzene, HQ or BQ for 1, 12 and
24h did not demonstrate induction of CYP1A1 protein expression. Dichlorodihydrofluorescein staining of cells
exposed to benzene, HQ or BQ revealed that the presence of the AhR did not affect BQ and HQ induced ROS
production. These results indicate that the involvement of the AhR in benzene toxicity does not seem to be through
classical activation of this receptor or through interference of oxidative stress pathways. Abstract: PubMed
Badham HJ, Winn LM.; Toxicology. 229 (3): 17785 (2007)
from HSDB
NADPH:quinone oxidoreductase 1 NQO1 may perform multiple functions within the cell. It is known to detoxify
benzenederived quinones and generate antioxidant forms of ubiquinone and Vitamin E. Recently suggested roles for
NQO1 which may have relevance for mechanisms underlying benzene toxicity include modulation of cellular redox
balance, direct scavenging of superoxide, stabilization of p53 and stabilization of microtubules. The NQO1*2
polymorphism is a single nucleotide polymorphism, a C to T change at position 609 of the NQO1 cDNA coding for a
proline to serine change at position 187 of the amino acid structure of the protein. The mutant NQO1*2 protein is
rapidly degraded by the ubiquitin proteasomal system resulting in a lack of NQO1 protein in individuals carrying the
NQO1*2/*2 genotype. The NQO1*2 polymorphism predisposes to benzene toxicity and to various forms of leukemias.
NQO1knockout animals demonstrate myeloid hyperplasia and increased benzeneinduced hematotoxicity. NQO1 is
not present in freshly isolated human bone marrow hematopoietic cells but can be induced by benzene metabolites.
Increases in NQO1 were not observed in NQO1*2/*2 hematopoietic cells, presumably because of the instability of the
NQO1*2 protein, suggesting that cells with this genotype would not benefit from any protective effects of NQO1.
NQO1 is present in human bone marrow stroma and particularly in endothelial cells. Studies of the functions and
distribution of NQO1 in human bone marrow may provide clues to mechanisms underlying benzene toxicity. Abstract:
PubMed
Ross D; Chem Biol Interact. 153154:13746 (2005)
from HSDB
Reactive metabolites formed from benzene include benzene oxide, trans,trans muconaldehyde, quinones, thiol
adducts, phenolic metabolites and oxygen radicals. Susceptibility to the toxic effects of benzene has been suggested
to occur partly because of polymorphisms in enzymes involved in benzene metabolism which include cytochrome
P450 2E1, epoxide hydrolases, myeloperoxidase, glutathioneStransferases and quinone reductases. However,
susceptibility factors not directly linked to benzene metabolism have also been associated with its toxicity and include
p53, proteins involved in DNA repair, genomic stability and expression of cytokines and/or cell adhesion molecules. In
this work, /the authors/ examine potential relationships between metabolic and nonmetabolic susceptibility factors
using the enzyme NADPH:quinone oxidoreductase NQO1 as an example. NQO1 may also impact pathways in
addition to metabolism of quinones due to proteinprotein interactions or other mechanisms related to NQO1
activity. NQO1 has been implicated in stabilizing p53 and in maintaining microtubule integrity. Inhibition or
knockdown of NQO1 in bone marrow endothelial cells has been found to lead to deficiencies of Eselectin, ICAM1
and VCAM1 adhesion molecule expression after TNFalpha stimulation. These examples illustrate how the metabolic
susceptibility factor NQO1 may influence nonmetabolic susceptibility pathways for benzene toxicity.[Ross D, Zhou H;
Chem Biol Interact. 184 12: 2228 2010] Full text: PMC2846242 Abstract: PubMed
from HSDB
9.6 Human Metabolite Information
9.6.1 Metabolite Description
Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. Chronic benzene exposure produces
hematotoxicity, bone marrow dysplasia Displasia is a preneoplastic or precancerous change. PMID: 16183116. It is
used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous
system damage acutely and is carcinogenic. It was formerly used as parasiticide.
9.6.2 Biofluid Locations
1. Blood
2. Feces
3. Saliva
9.6.3 Tissue Locations
1. Bone Marrow
2. Liver
3. Lymphocyte
4. Skin
10 Use and Manufacturing
10.1 Uses
Chemical Classification
Hydrocarbons contain hydrogen and carbon atoms, Volatile organic compounds
from CDCATSDR Toxic Substances Portal
Benzene is used as a constituent in motor fuels; as a solvent for fats, waxes, resins, oils, inks, paints, plastics, and
rubber; in the extraction of oils from seeds and nuts; and in photogravure printing. It is also used as a chemical
intermediate. Benzene is also used in the manufacture of detergents, explosives, pharmaceuticals, and dyestuffs.
from EPA Air Toxics
JECFA Functional Classes

Food Additives: EXTRACTION_SOLVENT
Solvent
from USGS Columbia Environmental Research Center
10.1.1 Industry Uses
1. Adhesives and sealant chemicals

2. Fuels and fuel additives
3. Intermediates
4. Ion exchange agents
5. Laboratory chemicals
6. Plasticizers
7. Processing aids, not otherwise listed
8. Processing aids, specific to petroleum production
9. Solvents for cleaning or degreasing
from EPA Chemicals under the TSCA
10.1.2 Consumer Uses
1. Adhesives and Sealants

2. Automotive Care Products
3. Cleaning and Furnishing Care Products
4. Fuels and Related Products
5. Lubricants and Greases
6. Paints and Coatings
7. Plastic and Rubber Products not covered elsewhere
from EPA Chemicals under the TSCA
10.2 Methods of Manufacturing

Worldwide, ~30% of commercial benzene is produced by catalytic reforming, a process in which aromatic molecules
are produced from the dehydrogenation of cycloparaffins, dehydroisomerization of alkyl cyclopentanes, and the
cyclization and subsequent dehydrogenation of paraffins. The feed to the catalytic reformer may be a straightrun,
hydrocracked, or thermally cracked naphtha fraction in the C6 to 200 deg C range. If benzene is the main product
desired, a narrow naphtha cut of 71104 deg C is fed to the reformer. The reforming catalyst most frequently consists
of platinumrhenium on a high surface area alumina support. The reformer operating conditions and type of
feedstock largely determine the amount of benzene that can be produced. The benzene product is most often
recovered from the reformate by solvent extraction techniques.
Fruscella W; Benzene. KirkOthmer Encyclopedia of Chemical Technology (19992014). John Wiley & Sons, Inc. Online Posting Date:
June 10, 2002
from HSDB
Benzene is produced from the hydrodemethylation of toluene under catalytic or thermal conditions. The main
catalytic hydrodealkylation processes are Hydeal and DETOL. Two widely used thermal processes are HDA and THD.
These processes contribute 2530% of the world's total benzene supply. In catalytic toluene hydrodealkylation,
toluene is mixed with a hydrogen stream and passed through a vessel packed with a catalyst, usually supported
chromium or molybdenum oxides, platinum or platinum oxides, on silica or alumina. The operating temperatures
range from 500 to 595 deg C and pressures are usually 46 MPa 4060 atm. The reaction is highly exothermic and
the temperature is controlled by injection of quench hydrogen at several places along the reaction. Conversions per
pass typically reach 90% and selectivity to benzene is often >95%. The catalytic process occurs at lower temperatures
and offers higher selectivities but requires frequent regeneration of the catalyst. Products leaving the reactor pass
through a separator where unreacted hydrogen is removed and recycled to the feed. Further fractionation separates
methane from the benzene product.
June 10, 2002
from HSDB
The steam cracking of heavy naphthas or light hydrocarbons such as propane or butane to produce ethylene yields a
liquid byproduct rich in aromatic content called pyrolysis gasoline, dripolene, or drip oil. A typical pyrolysis gasoline
contains up to 65% aromatics, 50% of which is benzene. Approximately 3035% of benzene produced worldwide is
derived from pyrolysis gasoline. The remainder of the product is composed of mono and diolefins. These olefinic
substances are removed by a mild hydrogenation step. Following hydrogenation, the resulting pyrolysis gasoline is
used in motor gasoline. Alternatively, pure benzene could be recovered from the pyrolysis gasoline by solvent
extraction and subsequent distillation.
June 10, 2002
from HSDB
Two molecules of toluene are converted into one molecule of benzene and one molecule of mixedxylene isomers in
a sequence called transalkylation or disproportionation. Economic feasibility of the process strongly depends on the
relative prices of benzene, toluene, and xylene. Operation of a transalkylation unit is practical only when there is an
excess of toluene and a strong demand for benzene. In recent years, xylene and benzene prices have generally been
higher than toluene prices so transalkylation is presently an attractive alternative to hydrodealkylation.
June 10, 2002
from HSDB
Benzene has been recovered from coal tar. The lowest boiling fraction is extracted with caustic soda to remove tar
acids. The base washed oil is then distilled and further purified by hydrodealkylation.
June 10, 2002
from HSDB
10.3 Impurities
Major impurities are toluene and xylene, others: phenol, thiophene, carbon disulfide, acetylnitrile, and pyridine.
NIOSH; Criteria Document: Benzene p.20 (1974) DHEW Pub No 74137
from HSDB
10.4 Formulations/Preparations
Nitration grade > 99% purity.
Environment Canada; Tech Info for Problem Spills: Benzene (Draft) p.20 (1981)
from HSDB
"Benzol 90" contains 8085% benzene, 1315% toluene, 23% xylene.

from HSDB
Grade: crude, straw color; motor; industrial pure 2C; nitration 1C; thiophenefree; 99 mole%; 99.94 mole%;
nanograde.
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 134
from HSDB
10.5 Consumption
Consumption by chemical industry in USA, 1977: 1.4 billion gallons annually.
Fishbein L; Pot Ind Carcin & Muta p.296 (1977) EPA 560/577005
from HSDB
Chem int for ethylbenzene, 49.1%; chem int for cumene, 18.4%; chem int for cyclohexane, 15.1%; chem int for
nitrobenzene, 4.5%; chem int for maleic anhydride, 2.8%; chem int for chlorobenzenes, 2.5%; chem int for detergent
alkylate, 2.4%; exports, 2.7%; other uses, 2.5% 1981 nongasoline uses
SRI Consulting. 2011 Directory of Chemical Producers United States. SRI Consulting, Menlo Park, CA 2011
from HSDB
Demand: 1980 1,586 Million Gal; /Projected demand for/ 1984: 1,708 Million Gal
Kavaler. Chem Market Reporter (1981)
from HSDB
BENZENE RANKED 17TH IN 1981 & 1982 IN THE TOP 50 CHEMICAL PRODUCTION: BILLIONS OF LB: 7.87 1982, 9.61
1981.
CHEMICAL & ENGINEERING NEWS; MAY 2: 11 (1983)
from HSDB
Ethylbenzene/styrene, 52%; cumene/phenol, 22%; clyclohexane, 15%; nitrobenzene/aniline, 4.5%; detergent alkylate,
2.5%; chlorobenzenes, maleic anhydride and other, 3%; exports, 1% 1984
CHEMICAL PROFILE: Benzene, (1984)
from HSDB
USA benzene demand /is projected to/ climb /from/ 3.8% in 1987, to 5.7 million tons, and reach 6 million tons in 1990
1987 and 1990
CHEM WEEK 140 (14): 14 (1987)
from HSDB
CHEMICAL PROFILE: Benzene. Ethylbenzene/styrene, 55%; cumene/phenol, 21%; cyclohexane, 14%;

nitrobenzene/aniline, 5%; detergent alkylate, 3%; chlorobenzenes, exports and others, 2%.
Kavaler AR; Chemical Marketing Reporter 231 (24): 49 (1987)
from HSDB
CHEMICAL PROFILE: Benzene. Demand: 1986: 1,603 million gal; 1987: 1,667 million gal; 1991 /projected/: 1,790 million
gal. Includes imports; 155 million gal were imported in 1986.
Kavaler AR; Chemical Marketing Reporter 231 (24): 49 (1987)
from HSDB
World benzene production rose to 6X10+6 tons 1.8X10+9 gallons in 1988. The United States is the largest producer
of benzene and accounts for about 30% of world production.
KirkOthmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991Present., p. V4
(92) 85
from HSDB
U.S. demand: 2,000 million gallons in 1995; 1,900 million gallons 1996; predicted 2,100 million gallons 2000.
Chemical Marketing Reporter; Chemical Profile Benzene. June 24 pp. 25 and 49 NY, NY: Schnell Pub Co. (1996)
from HSDB
10.6 U.S. Production

1967 9.6X10+8 gal data reported by tar distillers are not included
United States International Trade Commission. Synthetic Organic Chemicals United States Production and Sales, 1981. USITC
Publications 1291 Washington, DC: United States International Trade Commission, 1981., p. 10
from HSDB
1977 4.80X10+12 G
SRI
from HSDB
1980 1.5X10+9 gal data reported by tar distillers are not included
from HSDB
1981 4.3X10+11 GRAMS

Publications 1291 Washington, DC: United States International Trade Commission, 1981.
from HSDB
1981 1.3X10+9 gal all grades produced from lightoil distillates of tar and tar crudes
from HSDB
1982 3.55X10+12 G
SRI
from HSDB
1983 1.227X10+8 gallons

(92) 85
from HSDB
1984 1.312X10+8 gallons

(92) 85
from HSDB
1988 1.776X10+8 gallons from petroleum, 5.25X10+7 gallons from coal

(92) 85
from HSDB
1985 3.74X10+9 g 98100% pure from petroleum and natural gas

USITC. SYN ORG CHEMU.S. PROD/SALES 1985 p.19
from HSDB
1985 5.16X10+8 g 9097.9% pure from petroleum and natural gas

USITC. SYN ORG CHEMU.S. PROD/SALES 1985 p.19
from HSDB
1986 4.39X10+11 g
CHEM WEEK 140 (14): 14 (1987)
from HSDB
1986 1.39X10+9 gal

USITC. SYN ORG CHEMU.S. PROD/SALES. PRELIMINARY 1987
from HSDB
1987 1.59X10+9 gal est

USITC. SYN ORG CHEMU.S. PROD/SALES. PRELIMINARY 1987
from HSDB
1989 5,414,072,000 kg all grades

USITC Syn Org ChemU.S. Prod/Sales 1989 pg. 22 (1990)
from HSDB
Benzene ranks 16th in production volume for chemicals produced in the USA, with approx 9.9 billion lb being
produced in 1984, 9.1 billion lb in 1983, and 7.8 billion lb in 1982.
Toxicology and Carcinogenesis Studies of Benzene p.24 Report# 289 (1986) NIH Pub# 862545
from HSDB
1990 12.45 billion lb

Chem & Engineering News 70 (15): 17 (4/13/92)
from HSDB

from HSDB

from HSDB

from HSDB
Benzene is listed as a High Production Volume HPV chemical 65FR81686. Chemicals listed as HPV were produced in
or imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory
Update Rule. IUR 40 CFR part 710 subpart B; 51FR21438.
EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program. Benzene (71432). Available
from, as of January 29, 2014: http://www.epa.gov/hpv/pubs/general/opptsrch.htm
from HSDB
Production volumes for nonconfidential chemicals reported under the Inventory Update Rule.
Year Production Range pounds
1986 >1 billion
1990 >1 billion
1994 >1 billion
1998 >1 billion
2002 >1 billion
US EPA; Nonconfidential Production Volume Information Submitted by Companies for Chemicals Under the 19862002 Inventory
Update Rule (IUR). Benzene (71432). Available from, as of January 29, 2014: http://epa.gov/cdr/tools/data/2002vol.html
from HSDB
Production volume for nonconfidential chemicals reported under the 2006 Inventory Update Rule. Chemical:
Benzene. Aggregated National Production Volume: 1 billion pounds and greater.
US EPA; NonConfidential 2006 Inventory Update Reporting. National Chemical Information. Benzene (71432). Available from, as
of January 29, 2014: http://cfpub.epa.gov/iursearch/index.cfm
from HSDB
Nonconfidential 2012 Chemical Data Reporting CDR information on the production and use of chemicals
manufactured or imported into the United States. Chemical: Benzene. National Production Volume: 23,712,482,513
lb/yr.
USEPA/Pollution Prevention and Toxics; 2012 Chemical Data Reporting Database. Benzene (71432). Available from, as of January
30, 2014: http://java.epa.gov/oppt_chemical_search/
from HSDB
10.7 U.S. Imports

1978 2.26X10+11 G
SRI
from HSDB
1979 1.6 billion kg

DHHS/NTP; Third Annual Report On Carcinogens p.28 (1983) NTP 82330
from HSDB
1983 4.93X10+11 G
SRI
from HSDB
1985 4.96X10+11 g
BUREAU OF THE CENSUS. U.S. IMPORTS FOR CONSUMPTION AND GENERAL IMPORTS 1985 p. 1546
from HSDB
1986 4.72X10+11 g
CHEM WEEK 140 (14): 14 (1987)
from HSDB
1986 1.56X10+8 lb
BUREAU OF THE CENSUS. US IMPORTS FOR CONSUMPTION AND GENERAL IMPORTS 1986 p.1492
from HSDB
10.8 U.S. Exports

1978 1.52X10+11 G
SRI
from HSDB
1983 3.66X10+10 G
SRI
from HSDB
1979 1.3 million lb

DHHS/NTP; Third Annual Report On Carcinogens p.28 (1983) NTP 82330
from HSDB
1985 3.77X10+10 g
BUREAU OF THE CENSUS. U.S. EXPORTS, SCHEDULE E, 1985 p.269
from HSDB
Exports were thought to be less than 10 million gallons.

Chemical & Engineering News p.11 (2/9/87)
from HSDB
10.9 Sampling Procedures

Analyte: Benzene by portable GC; Matrix: air; Sampler: air bag Tedlar; Flow rate: 0.02 to 0.05 l/min or higher; Stability:
approx 4 hr
U.S. Department of Health and Human Services, Public Health Service. Centers for Disease Control, National Institute for
Occupational Safety and Health. NIOSH Manual of Analytical Methods, 3rd ed. Volumes 1 and 2 with 1985 supplement, and
revisions. Washington, DC: U.S. Government Printing Office, February 1984., p. V1 37001
from HSDB
Analyte: Benzene; Matrix: air; Sampler: Solid sorbent tube coconut shell charcoal, 100 mg/50 mg; Flow rate: approx
0.20 L/min; Vol: max: 30 L; Stability: at least 2 wk; Bulk sample: 1 to 10 mL, ship in separate containers from samples.
U.S. Department of Health and Human Services, Public Health Service. Centers for Disease Control, National Institute for
Occupational Safety and Health. NIOSH Manual of Analytical Methods, 3rd ed. Volumes 1 and 2 with 1985 supplement, and
revisions. Washington, DC: U.S. Government Printing Office, February 1984., p. V2 15001
from HSDB
11 Identification
11.1 Analytic Laboratory Methods

Method: NIOSH 1501, Issue 3; Procedure: gas chromatography with flame ionization detector; Analyte: benzene;
Matrix: air; Detection Limit: 0.5 ug/sample.
CDC; NIOSH Manual of Analytical Methods, 4th ed. Benzene (71432). Available from, as of January 31, 2014:
http://www.cdc.gov/niosh/docs/2003154/
from HSDB
Method: NIOSH 2549, Issue 1; Procedure: thermal desorption, gas chromatography, mass spectrometry; Analyte:
benzene; Matrix: air; Detection Limit: 100 ng per tube or less.
from HSDB
Method: NIOSH 3700, Issue 2; Procedure: gas chromatography portable, photoionization detector; Analyte: benzene;
Matrix: air; Detection Limit: 0.01 ppm for a 1mL injection.
from HSDB
Method: NIOSH 3800, Issue 1; Procedure: extractive fourier transform infrared FTIR spectrometry; Analyte: benzene;
Matrix: air; Detection Limit: 0.32 ppm for a 10 meter absorption pathlength.
from HSDB
Method: OSHA 12; Procedure: gas chromatography air samples, liquid chromatography bulk samples; Analyte:
benzene; Matrix: air; Detection Limit: air samples, 0.04 ppm; bulk samples, 0.01% by volume.
U.S. Department of Labor/Occupational Safety and Health Administration's Index of Sampling and Analytical Methods. Benzene
(71432). Available from, as of February 3, 2014: http://www.osha.gov/dts/sltc/methods/toc.html
from HSDB
Method: ASTM D5790; Procedure: gas chromatography/mass spectrometry; Analyte: benzene; Matrix: validated for
treated drinking water, wastewater, and ground water; Detection Limit: 0.19 ug/L.
National Environmental Methods Index; Analytical, Test and Sampling Methods. Benzene (71432). Available from, as of January
30, 2014: http://www.nemi.gov
from HSDB
Method: EPAEAD 602; Procedure: gas chromatography with photoionization detector; Analyte: benzene; Matrix:
municipal and industrial discharges; Detection Limit: 0.2 ug/L.
from HSDB
Method: EPAEAD 624; Procedure: gas chromatography/mass spectrometry; Analyte: benzene; Matrix: water;
Detection Limit: 4.4 ug/L.
from HSDB
Method: EPAEAD 1624; Procedure: gas chromatography/mass spectrometry; Analyte: benzene; Matrix: water;
Detection Limit: 10 ug/L.
from HSDB
Method: EPANERL 502.2; Procedure: gas chromatography with photoionization detector; Analyte: benzene; Matrix:
finished drinking water, raw source water, or drinking water in any treatment stage; Detection Limit: 0.01 ug/L.
from HSDB
Method: EPANERL 524.2; Procedure: gas chromatography/mass spectrometry; Analyte: benzene; Matrix: surface
water, ground water, and drinking water in any stage of treatment; Detection Limit: 0.03 ug/L.
from HSDB
Method: EPAOGWDW/TSC 524.3; Procedure: gas chromatography/mass spectrometry; Analyte: benzene; Matrix:
finished drinking waters; Detection Limit: 0.017 ug/L.
from HSDB
Method: EPARCA 5030C; Procedure: purge and trap; Analyte: benzene; Matrix: water; Detection Limit: not provided.
from HSDB
Method: EPARCA 8260B; Procedure: gas chromatography/mass spectrometry; Analyte: benzene; Matrix: various;
Detection Limit: not provided.
from HSDB
Method: Standard Methods 6200B; Procedure: gas chromatography/mass spectrometry; Analyte: benzene; Matrix:
water; Detection Limit: 0.03 ug/L.
from HSDB
Method: Standard Methods 6200C; Procedure: gas chromatography; Analyte: benzene; Matrix: water; Detection Limit:
0.01 ug/L.
from HSDB
Method: USGSNWQL O3115; Procedure: gas chromatography/mass spectrometry; Analyte: benzene; Matrix: water
and water suspendedsediment; Detection Limit: 3 ug/L.
from HSDB
Method: USGSNWQL O402403; Procedure: gas chromatography/mass spectrometry; Analyte: benzene; Matrix:
wholewater; Detection Limit: 0.0067 ug/L.
from HSDB
Method: USGSNWQL O412796; Procedure: gas chromatography/mass spectrometry; Analyte: benzene; Matrix:
surface or groundwater; Detection Limit: 0.031 ug/L.
from HSDB
GC/FID method to determine benzene in landfill vapors & soil. Adsorb landfill vapors on carbon in glass tubes; desorb
with carbon disulfide: Colenutt BA, Davies DN; Int J Environ Anal Chem 7: 2239 1980. Sparge soil sample with
nitrogen; trap in Tenax GC tube; limit of detection 0.1 ug/kg. Fentiman AF et al; Environmental Monitoring Benzene
PB295 641 prepared for USEPA by Battelle Columbus Lab, Springfield, Va, Natl Tech Info Ser, pp 915, 26110
1979.
from HSDB
11.2 Clinical Laboratory Methods

Volatile cmpd such as benzene are separated from blood or tissue homogenate directly on gaschromatographic
column & detected using a flame ionization detector. High volatility permits gas chromatograph to be operated at
relatively low temp. The nonvolatile & high boiling components of the biological matrix are left behind in the injection
port. This insures long column life & requires only occasional cleaning of the injection chamber: Baker RN et al; Toxic
volatiles in alcoholic coma; Bull Los Angles County Neurol Soc 33: 140 1968; Wallace JE, Dahl EV; Rapid vapor phase
method for determining ethanol in blood & urine by gas chromatography; Am J Clin Pathol 46: 152 1966.
Sunshine, Irving (ed.) Methodology for Analytical Toxicology. Cleveland: CRC Press, Inc., 1975., p. 378
from HSDB
GLC & colorimetric phenol metabolite methods are used to determine benzene in serum, urine, & breath.
Conventional reference range: >1.0 mg/L toxic concn for serum; <10.0 mg/L as phenol, >75.0 mg/L toxic concn as
phenol for urine. Internationally recommended conc reference range is: >13 umol/L toxic concn for serum; <106
umol/L as phenol, >795 umol/L toxic concn as phenol for urine. Substances producing phenol as a metabolite can
interfere with color assay.
Tietz, N.W. (ed.). Clinical Guide to Laboratory Tests. Philadelphia, PA: W.B. Saunders Co., 1983., p. 76
from HSDB
GC/MS method to determine benzene in adipose tissue, brain, kidney, liver, lung, muscle, pancreas, & spleen; treat
sample with chlorobenzene, ethanol & water at 60 deg C; inject vapor phase into gas chromatograph: Nagata T et al;
Koenshulyo Masu Kenkyukai 3: 7782 1978, Chem Abstr 92: 192082X.
from HSDB
The urinary metabolites isolated by DEAE Sephadex A24 anionexchange chromatography from mice treated with
radiolabeled benzene included phenol as the major component, as well as catechol, hydroquinone, and
phenylmercapturic acid.
Longacre SL et al; Adv Exp Med Biol 136A: 30717 (1982)
from HSDB
A sensitive HPLC method is described which separates urinary metabolites from benzenetreated male CD1 mice
phenol, trans, transmuconic acid and quinol in the 48 hr urine, accounted, respectively for 12.822.8, 1.84.7 and 1.5
3.7% of the orally administered single dose of benzene 880, 440, and 220 mg/kg body wt.
Gadel Karim et al; Xerobiotic 15: 21120 (1985)
from HSDB
Benzene is known to produce hematotoxicity in occupational exposure workers. This study examined the utility of
metabonomic biomarkers to ascertain subacute toxicity produced by benzene in male C3H/He mice. A 30d
intermittent collection of urine was obtained from mice in this experiment. The relative organ weights, blood
parameters, and bone marrow smears were examined to identify specific changes of benzeneinduced toxicity. In
addition, an integrated analytical approach based on liquid chromatography coupled with mass spectrometry LCMS
was developed to map metabolic responses in urine. Five endogenous metabolites, hypoxanthine, spermidine, 4
aminohippuric acid, indolelactic acid, and glutamylphenylalanine, were identified as potential biomarkers of benzene
induced toxicity, indicating that pathways of purine, spermidine, fatty acid, tryptophan, and peptides metabolism
might be disturbed in benzeneexposed mice. Our findings showed that the use of urine metabonomics was a more
sensitive tool to detect benzeneinduced toxicity compared to body weight or blood parameter changes. Abstract:
PubMed
Sun R et al; J Toxicol Environ Health A. 2012;75(18):116373
from HSDB
11.3 OSHA Chemical Sampling

Benzene
Naphtha Coal Tar

11.4 NIOSH Analytical Methods

VOLATILE ORGANIC COMPOUNDS SCREENING 2549
from NIOSH Manual of Analytical Methods
NAPHTHAS 1550
HYDROCARBONS, AROMATIC 1501

BENZENE by portable GC 3700

ORGANIC AND INORGANIC GASES BY EXTRACTIVE FTIR SPECTROMETRY 3800

12 Safety and Hazards
12.1 Hazards Identification
12.1.1 GHS Classification
Signal: Danger
GHS Hazard Statements
Aggregated GHS information from 37 notifications provided by 1378 companies to the ECHA C&L Inventory. Each
notification may be associated with multiple companies.
H225 99.78%: Highly Flammable liquid and vapor [Danger Flammable liquids Category 2]
H304 99.27%: May be fatal if swallowed and enters airways [Danger Aspiration hazard Category 1]
H315 99.93%: Causes skin irritation [Warning Skin corrosion/irritation Category 2]
H319 99.93%: Causes serious eye irritation [Warning Serious eye damage/eye irritation Category 2A]
H340 99.85%: May cause genetic defects [Danger Germ cell mutagenicity Category 1A, 1B]
H350 99.85%: May cause cancer [Danger Carcinogenicity Category 1A, 1B]
H372 99.2%: Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ
toxicity, repeated exposure Category 1]
H412 11.32%: Harmful to aquatic life with long lasting effects [Hazardous to the aquatic environment, longterm
hazard Category 3]
Information may vary between notifications depending on impurities, additives, and other factors. The percentage
value in parenthesis indicates the notified classification ratio from all companies. Only Hazard Codes with percentage
values above 10% are shown.
Precautionary Statement Codes

P201, P202, P210, P233, P240, P241, P242, P243, P260, P264, P270, P273, P280, P281, P301+P310, P302+P352,
P303+P361+P353, P305+P351+P338, P308+P313, P314, P321, P331, P332+P313, P337+P313, P362, P370+P378,
P403+P235, P405, and P501
The corresponding statement to each Pcode can be found here.
View all 5 GHS Classification entries
12.1.2 Health Hazard
Dizziness, excitation, pallor, followed by flushing, weakness, headache, breathlessness, chest constriction, nausea, and
vomiting. Coma and possible death. USCG, 1999
Carcinogen, Mutagen, Flammable 3rd degree

from NJDOH RTK Hazardous Substance List
12.1.3 Fire Hazard
Behavior in Fire: Vapor is heavier than air and may travel considerable distance to a source of ignition and flash back.
USCG, 1999
Highly flammable.
from ILOICSC
12.1.4 Explosion Hazard
Vapour/air mixtures are explosive. Risk of fire and explosion. See Chemical Dangers.
from ILOICSC
12.1.5 Hazards Summary
Benzene is a colorless liquid with a sweet odor. It evaporates into the air very quickly and dissolves slightly in water. It
is highly flammable and is formed from both natural processes and human activities. Benzene is widely used in the
United States; it ranks in the top 20 chemicals for production volume. Some industries use benzene to make other
chemicals which are used to make plastics, resins, and nylon and synthetic fibers. Benzene is also used to make some
types of rubbers, lubricants, dyes, detergents, drugs, and pesticides. Natural sources of benzene include volcanoes
and forest fires. Benzene is also a natural part of crude oil, gasoline, and cigarette smoke.
Benzene is found in the air from emissions from burning coal and oil, gasoline service stations, and motor vehicle
exhaust. Acute shortterm inhalation exposure of humans to benzene may cause drowsiness, dizziness, headaches,
as well as eye, skin, and respiratory tract irritation, and, at high levels, unconsciousness. Chronic longterm inhalation
exposure has caused various disorders in the blood, including reduced numbers of red blood cells and aplastic
anemia, in occupational settings. Reproductive effects have been reported for women exposed by inhalation to high
levels, and adverse effects on the developing fetus have been observed in animal tests. Increased incidence of
leukemia cancer of the tissues that form white blood cells have been observed in humans occupationally exposed to
benzene. EPA has classified benzene as known human carcinogen for all routes of exposure.
from EPA Air Toxics
12.1.6 Fire Potential
A dangerous fire hazard when exosed to heat or flame. ... Ignites on contact with sodium peroxide + water, dioxygenyl
tetrafluoroborate, iodine heptafluoride, and dioxygen difluoride.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. WileyInterscience, Wiley & Sons, Inc. Hoboken,
NJ. 2004., p. 360
from HSDB
12.1.7 Skin, Eye, and Respiratory Irritations
A severe eye and moderate skin irritant.

NJ. 2004., p. 360
from HSDB
Skin irritation has been noted at occupational exposures of greater than 60 ppm for up to three weeks.
from HSDB
Direct exposure of the eyes, skin, or lungs to benzene can cause tissue injury and irritation.
CDC; Emergency Preparedness and Response: Facts about Benzene; Available from, as of February 21, 2014:
http://www.bt.cdc.gov/agent/benzene/basics/facts.asp
from HSDB
12.2 Safety and Hazard Properties
12.2.1 LEL
1.4 % NTP, 1992

1.2%
12.2.2 UEL
8 % NTP, 1992
7.8%
12.2.3 Flammability
Lower flammable limit: 1.2% by volume; Upper flammable limit: 7.8% by volume
from HSDB
Class IB Flammable Liquid: Fl.P. below 73F and BP at or above 100F.

12.2.4 Critical Temperature
Critical temperature: 562.0 K; critical pressure: 5.90 MPa; critical volume: 257 cu cm/mol
from HSDB
12.2.5 Critical Pressure
Critical temperature: 562.0 K; critical pressure: 5.90 MPa; critical volume: 257 cu cm/mol
from HSDB
12.2.6 NFPA Hazard Classification
Health: 1. 1= Material that, on exposure, would cause significant irritation, but only minor residual injury, including
those requiring the use of an approved airpurifying respirator. These materials are only slightly hazardous to health
and only breathing protection is needed.
from HSDB
Flammability: 3. 3= This degree includes Class IB and IC flammable liquids and materials that can be easily ignited
under almost all normal temperature conditions. Water may be ineffective in controlling or extinguishing fires in such
materials.
from HSDB
instability: 0. 0= This degree includes materials that are normally stable, even under fire exposure conditions, and that
do not react with water. Normal fire fighting procedures may be used.
from HSDB
12.2.7 NFPA Fire Rating
3
from CAMEO Chemicals, OSHA Occupational Chemical DB
12.2.8 NFPA Health Rating
2
from CAMEO Chemicals, OSHA Occupational Chemical DB
12.2.9 Physical Dangers
The vapour is heavier than air and may travel along the ground; distant ignition possible. As a result of flow, agitation,
etc., electrostatic charges can be generated.
from ILOICSC
12.2.10 Chemical Dangers
NIOSH usually recommends that occupational exposures to carcinogens be limited to the lowest feasible
concentration.
from HSDB
Reacts violently with oxidants, nitric acid, sulfuric acid and halogens. This generates fire and explosion hazard. Attacks
plastics and rubber.
from ILOICSC
12.2.11 Explosive Limits and Potential
Lower 1.4%, upper 8.0%

NJ. 2004., p. 360
from HSDB
vol% in air: 1.28.0

from ILOICSC
12.2.12 OSHA Standards
Permissible exposure limits PELs 1 Timeweighted average limit TWA. The employer shall assure that no
employee is exposed to an airborne concentration of benzene in excess of one part of benzene per million parts of air
1 ppm as an 8 hr TWA. 2 Shortterm exposure limit STEL. The employer shall assure that no employee is exposed
to an airborne concentration of benzene in excess of 5 ppm as averaged over any 15 min period.
29 CFR 1910.1028(c) (USDOL); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations.
Available from, as of January 28, 2014: http://www.ecfr.gov/cgibin/ECFR?page=browse
from HSDB
Permissible Exposure Limit: Table Z2 8hr Time Weighted Avg: 10 ppm. This standard applies to the industry
segments exempt from the 1 ppm 8hour TWA and 5 ppm STEL of the benzene standard at 1910.1028.
29 CFR 1910.1000 (USDOL); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available
from, as of January 28, 2014: http://www.ecfr.gov/cgibin/ECFR?page=browse
from HSDB
Permissible Exposure Limit: Table Z2 Acceptable Ceiling Concentration: 25 ppm. This standard applies to the industry
segments exempt from the 1 ppm 8hour TWA and 5 ppm STEL of the benzene standard at 1910.1028.
from HSDB
Permissible Exposure Limit: Table Z2 Acceptable maximum peak above the acceptable ceiling concentration for an 8
hour shift. Concentration: 50 ppm. Maximum Duration: 10 minutes. This standard applies to the industry segments
exempt from the 1 ppm 8hour TWA and 5 ppm STEL of the benzene standard at 1910.1028.
from HSDB
12.2.13 NIOSH Recommendations
NIOSH usually recommends that occupational exposures to carcinogens be limited to the lowest feasible
concentration.
from HSDB
Recommended Exposure Limit: 10 Hour TimeWeighted Average: 0.1 ppm.

from HSDB
Recommended Exposure Limit: 15 Minute ShortTerm Exposure Limit: 1 ppm.

from HSDB
12.3 First Aid Measures
12.3.1 First Aid
EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline
solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any
ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY
transport the victim after flushing eyes to a hospital even if no symptoms such as redness or irritation develop. SKIN:
IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all
affected skin areas thoroughly with soap and water. IMMEDIATELY call a hospital or poison control center even if no
symptoms such as redness or irritation develop. IMMEDIATELY transport the victim to a hospital for treatment after
washing the affected areas. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air.
IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms such as
wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest develop. Provide proper
respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, SelfContained Breathing
Apparatus SCBA should be used; if not available, use a level of protection greater than or equal to that advised
under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. Volatile chemicals have a high risk of being
aspirated into the victim's lungs during vomiting which increases the medical problems. If the victim is conscious and
not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control
center. IMMEDIATELY transport the victim to a hospital. If the victim is convulsing or unconscious, do not give
anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than
the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. OTHER: Since this chemical is
a known or suspected carcinogen you should contact a physician for advice regarding the possible long term health
effects and potential recommendation for medical monitoring. Recommendations from the physician will depend
upon the specific compound, its chemical, physical and toxicity properties, the exposure level, length of exposure, and
the route of exposure. NTP, 1992
EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline
solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any
ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY
transport the victim after flushing eyes to a hospital even if no symptoms such as redness or irritation develop. SKIN:
IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all
affected skin areas thoroughly with soap and water. IMMEDIATELY call a hospital or poison control center even if no
symptoms such as redness or irritation develop. IMMEDIATELY transport the victim to a hospital for treatment after
washing the affected areas. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air.
IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms such as
wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest develop. Provide proper
respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, SelfContained Breathing
Apparatus SCBA should be used; if not available, use a level of protection greater than or equal to that advised
under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. Volatile chemicals have a high risk of being
aspirated into the victim's lungs during vomiting which increases the medical problems. If the victim is conscious and
not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control
center. IMMEDIATELY transport the victim to a hospital. If the victim is convulsing or unconscious, do not give
anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than
the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. OTHER: Since this chemical is
a known or suspected carcinogen you should contact a physician for advice regarding the possible long term health
effects and potential recommendation for medical monitoring. Recommendations from the physician will depend
upon the specific compound, its chemical, physical and toxicity properties, the exposure level, length of exposure, and
the route of exposure. NTP, 1992
Eye: If this chemical contacts the eyes, immediately wash the eyes with large amounts of water, occasionally lifting the
lower and upper lids. Get medical attention immediately. Contact lenses should not be worn when working with this
chemical. Skin: If this chemical contacts the skin, promptly wash the contaminated skin with soap and water. If this
chemical penetrates the clothing promptly remove the clothing and wash the skin with soap and water. Get medical
attention promptly. Breathing: If a person breathes large amounts of this chemical, move the exposed person to fresh
air at once. If breathing has stopped, perform mouthtomouth resuscitation. Keep the affected person warm and at
rest. Get medical attention as soon as possible. Swallow: If this chemical has been swallowed, get medical attention
immediately. NIOSH, 1997
See procedures
Eye:Irrigate immediately
Skin:Soap wash immediately
Breathing:Respiratory support
Swallow:Medical attention immediately
12.3.2 Inhalation First Aid
Fresh air, rest. Refer for medical attention.

from ILOICSC
12.3.3 Skin First Aid
Remove contaminated clothes. Rinse skin with plenty of water or shower. Refer for medical attention .
from ILOICSC
12.3.4 Eye First Aid
First rinse with plenty of water for several minutes remove contact lenses if easily possible, then refer for medical
attention.
from ILOICSC
12.3.5 Ingestion First Aid
Rinse mouth. Do NOT induce vomiting. Refer for medical attention .

from ILOICSC
12.4 Fire Fighting Measures

Approach fire from upwind to avoid hazardous vapors. Use water spray, dry chemical, foam, or carbon dioxide. Use
water spray to keep fireexposed containers cool.
from HSDB
If material on fire or involved in fire: Do not extinguish fire unless flow can be stopped. Use water in flooding
quantities as fog. Solid streams of water may spread fire. Cool all affected containers with flooding quantities of water.
Apply water from as far a distance as possible. Use foam, dry chemical, or carbon dioxide.
Association of American Railroads; Bureau of Explosives. Emergency Handling of Hazardous Materials in Surface Transportation.
Association of American Railroads, Pueblo, CO. 2005, p. 111
from HSDB
Suitable extinguishing media: Use water spray, alcoholresistant foam, dry chemical or carbon dioxide.
from HSDB
Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.
from HSDB
Use water spray to cool unopened containers.

from HSDB
12.4.1 Fire Fighting
Excerpt from ERG Guide 130 [Flammable Liquids WaterImmiscible / Noxious]: CAUTION: All these products have a
very low flash point: Use of water spray when fighting fire may be inefficient. SMALL FIRE: Dry chemical, CO2, water
spray or regular foam. LARGE FIRE: Water spray, fog or regular foam. Do not use straight streams. Move containers
from fire area if you can do it without risk. FIRE INVOLVING TANKS OR CAR/TRAILER LOADS: Fight fire from maximum
distance or use unmanned hose holders or monitor nozzles. Cool containers with flooding quantities of water until
well after fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of
tank. ALWAYS stay away from tanks engulfed in fire. For massive fire, use unmanned hose holders or monitor nozzles;
if this is impossible, withdraw from area and let fire burn. ERG, 2016
Use foam, water spray, carbon dioxide, powder.

from ILOICSC
Do not extinguish fire unless flow can be stopped. Use water in flooding quantities as fog. Solid streams of water may
spread fire. Cool all affected containers with flooding quantities of water. Apply water from as far a distance as
possible. Use foam, dry chemical, or carbon dioxide. AAR, 1999
Do not extinguish fire unless flow can be stopped. Use water in flooding quantities as fog. Solid streams of water may
be ineffective. Cool all affected containers with flooding quantities of water. Apply water from as far a distance as
possible. Use foam, dry chemical, or carbon dioxide. AAR, 1999
12.4.2 Explosion Fire Fighting
In case of fire: keep drums, etc., cool by spraying with water.

from ILOICSC
12.4.3 Other Fire Fighting Hazards
Vapors are heavier than air and may travel to a source of ignition & flash back. Liquid floats on water and may travel
to a source of ignition and spread fire.
from HSDB
Special hazards arising from the substance or mixture: Carbon oxides Flash back possible over considerable distance.
Container explosion may occur under fire conditions.
from HSDB
12.5 Accidental Release Measures
12.5.1 Isolation and Evacuation
Excerpt from ERG Guide 130 [Flammable Liquids WaterImmiscible / Noxious]: As an immediate precautionary
measure, isolate spill or leak area for at least 50 meters 150 feet in all directions. LARGE SPILL: Consider initial
downwind evacuation for at least 300 meters 1000 feet. FIRE: If tank, rail car or tank truck is involved in a fire,
ISOLATE for 800 meters 1/2 mile in all directions; also, consider initial evacuation for 800 meters 1/2 mile in all
directions. ERG, 2016
12.5.2 Spillage Disposal
Remove all ignition sources. Evacuate danger area! Consult an expert! Personal protection: complete protective
clothing including selfcontained breathing apparatus. Do NOT wash away into sewer. Do NOT let this chemical enter
the environment. Collect leaking and spilled liquid in sealable containers as far as possible. Absorb remaining liquid in
sand or inert absorbent. Then store and dispose of according to local regulations.
from ILOICSC
12.5.3 Cleanup Methods
For spills on water, contain with booms or barriers, use surface acting agents to thicken spilled materials. Remove
trapped materials with suction hoses.
USEPA; Methods to Treat, Control and Monitor Spilled Hazardous Materials, EPA670/275042 (1975) EPA 670/275042
from HSDB
Small spills of benzene can be taken up by sorption on carbon or synthetic sorbent resins. Flush area with water. For
large quantities, if response is rapid, benzene can be skimmed off the surface. Straw may be used to mop slicks.
USEPA; Intermedia Priority Pollutant Guidance Documents p.81 (July, 1982)
from HSDB
PRECAUTIONS FOR "CARCINOGENS": A highefficiency particulate arrestor HEPA or charcoal filters can be used to
minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms. ...
Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating
maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal. ... The
plastic bag should be sealed immediately. ... The sealed bag should be labelled properly. ... Waste liquids ... should be
placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once
filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated. ... The plastic bag should
also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical
destruction, or in specially designed incinerators. /Chemical Carcinogens/
Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.).
Handling Chemical Carcinogens in the Laboratory: Problems of Safety. IARC Scientific Publications No. 33. Lyon, France:
International Agency for Research on Cancer, 1979., p. 15
from HSDB
Eliminate all ignition sources. Stop or control the leak, if this can be done without undue risk. Use water spray to cool
and disperse vapors, protect personnel, and dilute spills to form nonflammable mixtures. Absorb in noncombustible
material for proper disposal. Control runoff and isolate discharged material for proper disposal.
from HSDB
Environmental considerations: Land spill: Dig a pit, pond, lagoon, holding area to contain liquid or solid material. /SRP:
If time permits, pits, ponds, lagoons, soak holes, or holding areas should be sealed with an impermeable flexible
membrane liner./ Dike surface flow using soil, sand bags, foamed polyurethane, or foamed concrete. Absorb bulk
liquid with fly ash, cement powder, or commercial sorbents. Apply appropriate foam to diminish vapor and fire
hazard.
from HSDB
Environmental considerations: Water spill: Use natural barriers or oil spill control booms to limit spill travel. Use
surface active agent eg detergent, soaps, alcohols, if approved by EPA. Inject "universal" gelling agent to solidify
encircled spill and increase effectiveness of booms. If dissolved, in region of 10 ppm or greater concentration, apply
activated carbon at ten times the spilled amount. Remove trapped material with suction hoses. Use mechanical
dredges or lifts to remove immobilized masses of pollutants and precipitates.
from HSDB
Environmental considerations: Air spill: Apply water spray or mist to knock down vapors.
from HSDB
Accidental Release Measures. Personal precautions, protective equipment and emergency procedures: Use personal
protective equipment. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Remove all sources of
ignition. Evacuate personnel to safe areas. Beware of vapours accumulating to form explosive concentrations. Vapours
can accumulate in low areas. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let
product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and
cleaning up: Contain spillage, and then collect with an electrically protected vacuum cleaner or by wetbrushing and
place in container for disposal according to local regulations
from HSDB
Control of environmental exposure: Prevent further leakage or spillage if safe to do so. Do not let product enter
drains. Discharge into the environment must be avoided.
from HSDB
12.5.4 Disposal Methods
Generators of waste equal to or greater than 100 kg/mo containing this contaminant, EPA hazardous waste number
F005, U019, D018, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.
40 CFR 240280, 300306, 702799 (USEPA); U.S. National Archives and Records Administration's Electronic Code of Federal
Regulations. Available from, as of November April 6, 2014: http://www.ecfr.gov
from HSDB
SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites
should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations
shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or
discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and
assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker
exposure inhalation, dermal and ingestion as well as fate during treatment, transfer and disposal. If it is not
practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261,
specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.
from HSDB
Biodegradation, incineration: Benzene is biodegradable. Diluted aqueous soln, therefore, are drained into sewage
treatment plants and decomposed there by anaerobic bacteria. Solvent mixtures and sludges of higher concn are
burnt in special waste incinerators if a recovery process is uneconomical.
United Nations. Treatment and Disposal Methods for Waste Chemicals (IRPTC File). Data Profile Series No. 5. Geneva, Switzerland:
United Nations Environmental Programme, Dec. 1985., p. 100
from HSDB
This flammable liquid burns with a very smoky flame. Dilution with alcohol or acetone is suggested to minimize
smoke. Recommendable methods: Use as boiler fuel, incineration. Not recommendable: Landfill, discharge to sewer.
United Nations. Treatment and Disposal Methods for Waste Chemicals (IRPTC File). Data Profile Series No. 5. Geneva, Switzerland:
United Nations Environmental Programme, Dec. 1985., p. 100
from HSDB
Incinerate or dispose of via a licensed solvent recycling or disposal company.

from HSDB
PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for
all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of
carcinogencontaining waste. ... Summary of avail methods & recommendations ... /given/ must be treated as guide
only. /Chemical Carcinogens/
from HSDB
PRECAUTIONS FOR "CARCINOGENS": Total destruction ... by incineration may be only feasible method for disposal of
contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The
most efficient type ... is probably the gasfired type, in which a firststage combustion with a less than stoichiometric
air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic
solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust.
Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical
Carcinogens/
from HSDB
PRECAUTIONS FOR "CARCINOGENS": HEPA highefficiency particulate arrestor filters ... can be disposed of by
incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes
generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried
out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter &
misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem
carcinogens or their metabolites. /Chemical Carcinogens/
from HSDB
PRECAUTIONS FOR "CARCINOGENS": ... Small quantities of ... some carcinogens can be destroyed using chem
reactions ... but no general rules can be given. ... As a general technique ... treatment with sodium dichromate in
strong sulfuric acid can be used. The time necessary for destruction ... is seldom known ... but 12 days is generally
considered sufficient when freshly prepd reagent is used. ... Carcinogens that are easily oxidizable can be destroyed
with milder oxidative agents, such as sat soln of potassium permanganate in acetone, which appears to be a suitable
agent for destruction of hydrazines or of compounds containing isolated carboncarbon double bonds. Concn or 50%
aqueous sodium hypochlorite can also be used as an oxidizing agent. /Chemical Carcinogens/
from HSDB
PRECAUTIONS FOR "CARCINOGENS": Carcinogens that are alkylating, arylating or acylating agents per se can be
destroyed by reaction with appropriate nucleophiles, such as water, hydroxyl ions, ammonia, thiols & thiosulfate. The
reactivity of various alkylating agents varies greatly ... & is also influenced by sol of agent in the reaction medium. To
facilitate the complete reaction, it is suggested that the agents be dissolved in ethanol or similar solvents. ... No
method should be applied ... until it has been thoroughly tested for its effectiveness & safety on material to be
inactivated. For example, in case of destruction of alkylating agents, it is possible to detect residual compounds by
reaction with 44nitrobenzylpyridine. /Chemical Carcinogens/
from HSDB
Chemical Treatability of Benzene; Concentration Process: Biological Treatment; Chemical Classification: Aromatic; Scale
of Study: Full Scale; Type of Wastewater Used: Industrial Wastewater; Results of Study: 90100% reduction; treated by
aerated lagoon.
USEPA; Management of Hazardous Waste Leachate, EPA Contract No. 68032766 p.E42 (1982)
from HSDB
of Study: Full Scale; Type of Wastewater Used: Industrial Wastewater; Results of Study: 95100% reduction;
completely mixed activated sludge process.
from HSDB
of Study: Respirometer Study; Type of Wastewater Used: Domestic Wastewater; Results of Study: 1.441.45 g of
oxygen utilized/g of substrate added after 72 hr of oxidation.
from HSDB
of Study: Respirometer Study; Type of Wastewater Used: Domestic Wastewater; Results of Study: Oxygen uptake of 34
ppm oxygen/hr for 50 ppm chemical and 37 ppm oxygen/hr for 500 ppm chemical.
from HSDB
of Study: Full Scale; Type of Wastewater Used: Industrial Wastewater; Results of Study: 95100% reduction; Activated
sludge process.
from HSDB
Chemical Treatability of Benzene; Concentration Process: Stripping; Chemical Classification: Aromatic; Scale of Study:
Literature Review; Type of Wastewater Used: Unknown; Results of Study: Air and steam strippable.
from HSDB
Chemical Treatability of Benzene; Concentration Process: Stripping; Chemical Classification: Aromatic; Scale of Study:
Continuous Flow, Pilot Scale; Type of Wastewater Used: Synthetic Wastewater; Results of Study: 9599% reduction by
steam stripping; estimated cost of $3.35/1000 gal based on 0.03 MGD.
from HSDB
Chemical Treatability of Benzene; Concentration Process: Solvent Extraction; Chemical Classification: Aromatic; Scale of
Study: Literature Review; Type of Wastewater Used: Unknown; Results of Study: Extractable with suitable solvent.
from HSDB
Study: Laboratory Scale, Continuous Flow; Type of Wastewater Used: Industrial Wastewater; Results of Study: 290 ppm
@ 3 gal/hr, 97% reduction; Extraction of wastewater from styrene manufacture using isobutylane S/W= 0.107, RDC
extractor used.
from HSDB
Study: Laboratory Scale, Continuous Flow; Type of Wastewater Used: Industrial Wastewater; Results of Study: 71 ppm
@ 4.6 gal/hr, 96% reduction; extraction of ethylene quench wastewater using isobutylene S/W= 0.101 RDC extractor
used.
from HSDB
Study: Laboratory Scale, Continuous Flow; Type of Wastewater Used: Industrial Waste; Results of Study: 81 ppm @ 4.6
gal/hr, 97% reduction; extraction of ethylene quench wastewater using isobutane S/W= 0.097 RDC extractor used.
from HSDB
Chemical Treatability of Benzene; Concentration Process: Activated Carbon; Chemical Classification: Aromatic; Scale of
Study: Pilot Scale, Continuous Flow; Type of Wastewater Used: Hazardous Material Spill Results of Study: 90% removal
to 0.1 ppb effluent conc achieved in 8.5 min contact time; Spilled material treated using EPA's mobile treatment
trailer.
from HSDB
Study: Isotherm Test; Type of Wastewater Used: Pure Compound; Results of Study: 0.7 mg/g carbon capacity.
from HSDB
Study: Isotherm Test; Type of Wastewater Used: Pure Compound; Results of Study: Isotherm kinetics were as follows:
Carbon: K= 26.8, l/n= 1.305; Filtrasorb: K= 18.5 l/n= 1.158; carbon dose mg/L required to reduce 1 mg/L to 0.1 mg/L;
Daro678 Filtrasorb705.
from HSDB
Study: Isotherm Test; Type of Wastewater Used: Pure Compound; Results of Study: 95% reduction, 21 ppm final concn,
0.080 g/g carbon capacity; Carbon dose with 5 g/l Westvaco Nuchar.
from HSDB
Study: Literature Review; Type of Wastewater Used: Industrial Wastewater; Results of Study: Effluent concn of 30 ppm
TOC achieved; 98% removal; at contact time of 55 min 0.15 MGD flow; pretreatment including pH adjustment.
from HSDB
Study: Isotherm Test; Type of Wastewater Used: Pure Compound; Results of Study: Effluent Character ppm: 500, 95%
removal; 250, 91% removal; 50, 60% removal; 24 hr contact time, carbon dose was 10 times chemical concn.
from HSDB
Study: Literature Review; Type of Wastewater Used: Unknown; Results of Study: 95% removal at 0.5% carbon dose.
from HSDB
A good candidate for liquid injection incineration at a temperature range of 650 to 1,600 deg C and a residence time
of 0.1 to 2 seconds. A good candidate for rotary kiln incineration at a temperature range of 820 to 1,600 deg C and
residence times of seconds for liquids and gases, and hours for solids. A good candidate for fluidized bed incineration
at a temperature range of 450 to 980 deg C and residence times of seconds for liquids and gases, and longer for
solids.
USEPA; Engineering Handbook for Hazardous Waste Incineration p.311 (1981) EPA 68033025
from HSDB
Fullscale activated carbon column treatment: Influent concn: 28,000 ug/L; Effluent concn: 1 < 10 ug/L with +99%
removal, 2 73 ug/L with 4880% removal.
Patterson JW; Industrial Wastewater Treatment Technolgy 2nd Edition p.336 (1985)
from HSDB
Waste treatment methods. Product: Burn in a chemical incinerator equipped with an afterburner and scrubber but
exert extra care in igniting as this material is highly flammable. Offer surplus and nonrecyclable solutions to a
licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material.
Contaminated packaging: Dispose of as unused product.
from HSDB
12.5.5 Other Preventative Measures
SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or
detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the
form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and
the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are
such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not
be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.
from HSDB
SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emmissions or
dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of
generation is both the most economical and safest method to minimize personnel exposure to airborne
contaminants.
from HSDB
PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or
utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if
worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably
using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for
cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use
of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/
from HSDB
PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear
protective suits preferably disposable, onepiece & closefitting at ankles & wrists, gloves, hair covering &
overshoes. ... Clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/
workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however,
gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when
working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of
distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/
from HSDB
PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out
under wellventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ...
procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... &
when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so
that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be
kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will
not occur. /Chemical Carcinogens/
from HSDB
PRECAUTIONS FOR "CARCINOGENS": Vertical laminarflow biological safety cabinets may be used for containment of
in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening
of the cabinet, & contaminated air plenums that are under positive pressure are leaktight. Horizontal laminarflow
hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be
used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun eg, with fume bomb &
label fixed to it, giving date of test & avg airflow measured. This test should be repeated periodically & after any
structural changes. /Chemical Carcinogens/
from HSDB
PRECAUTIONS FOR "CARCINOGENS": Principles that apply to chem or biochem lab also apply to microbiological &
cellculture labs. ... Special consideration should be given to route of admin. ... Safest method of administering volatile
carcinogen is by injection of a soln. Admin by topical application, gavage, or intratracheal instillation should be
performed under hood. If chem will be exhaled, animals should be kept under hood during this period. Inhalation
exposure requires special equipment. ... Unless specifically required, routes of admin other than in the diet should be
used. Mixing of carcinogen in diet should be carried out in sealed mixers under fume hood, from which the exhaust is
fitted with an efficient particulate filter. Techniques for cleaning mixer & hood should be devised before expt begun.
When mixing diets, special protective clothing &, possibly, respirators may be required. /Chemical Carcinogens/
from HSDB
PRECAUTIONS FOR "CARCINOGENS": When ... admin in diet or applied to skin, animals should be kept in cages with
solid bottoms & sides & fitted with a filter top. When volatile carcinogens are given, filter tops should not be used.
Cages which have been used to house animals that received carcinogens should be decontaminated. Cagecleaning
facilities should be installed in area in which carcinogens are being used, to avoid moving of ... contaminated /cages/.
It is difficult to ensure that cages are decontaminated, & monitoring methods are necessary. Situations may exist in
which the use of disposable cages should be recommended, depending on type & amt of carcinogen & efficiency
with which it can be removed. /Chemical Carcinogens/
from HSDB
PRECAUTIONS FOR "CARCINOGENS": To eliminate risk that ... contamination in lab could build up during conduct of
expt, periodic checks should be carried out on lab atmospheres, surfaces, such as walls, floors & benches, & ... interior
of fume hoods & airducts. As well as regular monitoring, check must be carried out after cleaningup of spillage.
Sensitive methods are required when testing lab atmospheres for chem such as nitrosamines. Methods ... should ...
where possible, be simple & sensitive. ... /Chemical Carcinogens/
from HSDB
PRECAUTIONS FOR "CARCINOGENS": Rooms in which obvious contamination has occurred, such as spillage, should
be decontaminated by lab personnel engaged in expt. Design of expt should ... avoid contamination of permanent
equipment. ... Procedures should ensure that maintenance workers are not exposed to carcinogens. ... Particular care
should be taken to avoid contamination of drains or ventilation ducts. In cleaning labs, procedures should be used
which do not produce aerosols or dispersal of dust, ie, wet mop or vacuum cleaner equipped with highefficiency
particulate filter on exhaust, which are avail commercially, should be used. Sweeping, brushing & use of dry dusters or
mops should be prohibited. Grossly contaminated cleaning materials should not be reused. ... If gowns or towels are
contaminated, they should not be sent to laundry, but ... decontaminated or burnt, to avoid any hazard to laundry
personnel. /Chemical Carcinogens/
from HSDB
PRECAUTIONS FOR "CARCINOGENS": Doors leading into areas where carcinogens are used ... should be marked
distinctively with appropriate labels. Access ... limited to persons involved in expt. ... A prominently displayed notice
should give the name of the Scientific Investigator or other person who can advise in an emergency & who can inform
others such as firemen on the handling of carcinogenic substances. /Chemical Carcinogens/
from HSDB
SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal
contact by personnel who handle, dispose, or clean the clothing. Quality assurance to ascertain the completeness of
the cleaning procedures should be implemented before the decontaminated protective clothing is returned for reuse
by the workers.
from HSDB
If material not on fire and not involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material
out of water sources and sewers. Build dikes to contain flow as necessary. Attempt to stop leak if without undue
personnel hazard. Use water spray to knockdown vapors.
from HSDB
Personnel protection: Avoid breathing vapors. Keep upwind. ... Do not handle broken packages unless wearing
appropriate personal protective equipment. Wash away any material which may have contacted the body with
copious amounts of water or soap and water.
from HSDB
The worker should immediately wash the skin when it becomes contaminated.
from HSDB
Work clothing that becomes wet should be immediately removed due to its flammability hazard i.e., for liquids with a
flash point <100 deg F.
from HSDB
Precautions for safe handling: Avoid contact with skin and eyes. Avoid inhalation of vapour or mist. Use explosion
proof equipment. Keep away from sources of ignition No smoking.Take measures to prevent the build up of
electrostatic charge.
from HSDB
Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands
before breaks and at the end of workday.
from HSDB
Gloves must be inspected prior to use. Use proper glove removal technique without touching glove's outer surface
to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws
and good laboratory practices. Wash and dry hands.
from HSDB
12.6 Handling and Storage
12.6.1 Nonfire Spill Response
Excerpt from ERG Guide 130 [Flammable Liquids WaterImmiscible / Noxious]: ELIMINATE all ignition sources no
smoking, flares, sparks or flames in immediate area. All equipment used when handling the product must be
grounded. Do not touch or walk through spilled material. Stop leak if you can do it without risk. Prevent entry into
waterways, sewers, basements or confined areas. A vaporsuppressing foam may be used to reduce vapors. Absorb or
cover with dry earth, sand or other noncombustible material and transfer to containers. Use clean, nonsparking tools
to collect absorbed material. LARGE SPILL: Dike far ahead of liquid spill for later disposal. Water spray may reduce
vapor, but may not prevent ignition in closed spaces. ERG, 2016
Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. Build dikes to
contain flow as necessary. Attempt to stop leak if without undue personnel hazard. Use water spray to knockdown
vapors. AAR, 1999
Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. Build dikes to
contain flow as necessary. Use water spray to knockdown vapors. Land spill: Dig a pit, pond, lagoon, holding area to
contain liquid or solid material. Dike surface flow using soil, sand bags, foamed polyurethane, or foamed concrete.
Water spill: Use natural barriers or oil spill control booms to limit spill travel. Remove trapped material with suction
hoses. Use mechanical dredges or lifts to remove immobilized masses of pollutants and precipitates. AAR, 1999
12.6.2 Safe Storage
Fireproof. Separated from food and feedstuffs, oxidants and halogens. Store in an area without drain or sewer access.
from ILOICSC
12.6.3 Storage Conditions
Keep in well closed containers in a cool place and away from fire.
from HSDB
PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practicable to lab in which carcinogens are to
be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one
section of cupboard, an explosionproof refrigerator or freezer depending on chemicophysical properties ... that
bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ...
Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/
from HSDB
Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and wellventilated
place. Containers which are opened must be carefully resealed and kept upright to prevent leakage.
from HSDB
12.7 Exposure Control and Personal Protection
12.7.1 REL
CARCINOGEN Ca
Ca TWA 0.1 ppm ST 1 ppm See Appendix A

12.7.2 PEL
SEE 29 CFR 1910.1028, FOR INDUSTRIES EXEMPT FROM THIS STANDARD THE PELs ARE LOCATED IN 29 CFR 1910.1
[1910.1028] TWA 1 ppm ST 5 ppm See Appendix F

12.7.3 PELTWA
1 ppm
100 ppm
400 mg/m3
12.7.4 PELSTEL
5 ppm
12.7.5 RELTWA
0.1 ppm
100 ppm
400 mg/m3
12.7.6 RELSTEL
1 ppm
12.7.7 IDLH
500 ppm ; A potential occupational carcinogen. NIOSH, 2016

500 ppm Ca
1000 ppm 10% of LEL

Ca [500 ppm]
See: 71432
12.7.8 Threshold Limit Values
8 hr Time Weighted Avg TWA: 0.5 ppm, skin; 15 min Short Term Exposure Limit STEL: 2.5 ppm, skin.
American Conference of Governmental Industrial Hygienists. Threshold Limit Values for Chemical Substances and Physical Agents
and Biological Exposure Indices. ACGIH, Cincinnati, OH 2014, p. 13
from HSDB
A1; Confirmed human carcinogen.

from HSDB
Biological Exposure Index BEI: Determinant: t,tmuconic acid in urine; Sampling Time: end of shift; BEI: 500 ug/g
creatinine; Notation: The determinant may be present in biological specimens collected from subjects who have not
been occupationally exposed, at a concentration which could affect interpretation of the result. Such background
concentrations are incorporated in the BEI value.
from HSDB
Biological Exposure Index BEI: Determinant: Sphenylmercapturic acid in urine; Sampling Time: end of shift; BEI: 25
ug/g creatinine. The determinant may be present in biological specimens collected from subjects who have not been
occupationally exposed, at a concentration which could affect interpretation of the result. Such background
concentrations are incorporated in the BEI value.
from HSDB
12.7.9 Other Occupational Permissible Levels
Belgium: TWA skin 30 mg/cu m, 10 ppm 1978; Czechoslovakia: TWA 50 mg/cu m, Ceiling 80 mg/cu m/10 min
1976; Finland: TWA skin 32 mg/cu m, 10 ppm 1975; Hungary: TWA 20 mg/cu m, may be exceeded 5 times/shift as
long as avg does not exceed value 1974; Poland: Ceiling skin 30 mg/cu m 1976; Romania: Maximum skin 50
mg/cu m 1975; Switzerland: TWA skin 6.5 mg/cu m, 2 ppm 1978; USSR: Ceiling skin 5 mg/cu m 1980;
Yugoslavia: Ceiling skin 50 mg/cu m, 15 ppm 1971.
from HSDB
Emergency Response Planning Guidelines ERPG: ERPG1 50 ppm no more than mild, transient effects for up to 1 hr
exposure; ERPG2 150 ppm without serious, adverse effects for up to 1 hr exposure; ERPG3 1000 ppm not life
threatening up to 1 hr exposure.
American Industrial Hygiene Association. The AIHA 1999 Emergency Response Planning Guidelines and Workplace Environmental
Exposure Level Guides Handbook. American Industrial Hygiene Association. Fairfax, VA 1999., p. 25
from HSDB
Australia: 5 ppm, Category 1, established human carcinogen 1990; Commission of the European Communities: 0.5
ppm corresponding to estimated lifetime risk of 0.253.3 excess leukemia cases per 1000 workers; Federal Republic
of Germany: no MAK, Group A1 carcinogen, capable of inducing malignant tumors in humans, skin, Technical Guiding
Concentration TRK, 1 ppm 1996; Sweden: 0.5 ppm, shortterm value, 3 ppm, 15 min, skin, carcinogenic 1991;
United Kingdom: 5 ppm 1997.
American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological
Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. BENZENE1
from HSDB
12.7.10 Sources and Potential Exposure
Individuals employed in industries that manufacture or use benzene may be exposed to the highest levels of benzene.
Benzene is found in emissions from burning coal and oil, motor vehicle exhaust, and evaporation from gasoline
service stations and in industrial solvents. These sources contribute to elevated levels of benzene in the ambient air,
which may subsequently be breathed by the public.
Tobacco smoke contains benzene and accounts for nearly half the national exposure to benzene.
Individuals may also be exposed to benzene by consuming contaminated water.
from EPA Air Toxics
12.7.11 Assessing Personal Exposure
Measurement of benzene in an individual's breath or blood or the measurement of breakdown products in the urine
phenol can estimate personal exposure. However, the tests must be done shortly after exposure and are not helpful
for measuring low levels of benzene.
from EPA Air Toxics
12.7.12 Occupational Exposure Limits
TLV: 0.5 ppm as TWA; 2.5 ppm as STEL; skin; A1 confirmed human carcinogen; BEI issued; ACGIH 2004. MAK:
Carcinogen category: 1; Germ cell mutagen group: 3A; DFG 2004.
from ILOICSC
12.7.13 Inhalation Risk
A harmful contamination of the air can be reached very quickly on evaporation of this substance at 20C.
from ILOICSC
12.7.14 Effects of Short Term Exposure
The substance is irritating to the eyes, skin and respiratory tract. If this liquid is swallowed, aspiration into the lungs
may result in chemical pneumonitis. The substance may cause effects on the central nervous system. This may result
in lowering of consciousness. Exposure far above the OEL could cause unconsciousness and death. If swallowed the
substance easily enters the airways and could result in aspiration pneumonitis.
from ILOICSC
12.7.15 Effects of Long Term Exposure
The substance defats the skin, which may cause dryness or cracking. The substance may have effects on the central
nervous system and immune system. The substance may have effects on the bone marrow. This may result in
anaemia. This substance is carcinogenic to humans. May cause heritable genetic damage to human germ cells. See
Notes.
from ILOICSC
12.7.16 Acceptable Daily Intakes
Insufficient data are available to calculate a oneday Health Advisory for benzene. The Tenday Health Advisory 0.235
mg/l is considered to be adequately protective for a oneday exposure as well. ... Longerterm Health Advisories have
not been calculated because of the carcinogenic potency of benzene.
from HSDB
12.7.17 Personal Protection
See protection codes

Skin:Prevent skin contact
Eyes:Prevent eye contact
Wash skin:When contaminated
Remove:When wet flammable
Change:No recommendation
Provide:Eyewash, Quick drench
12.7.18 Respirator Recommendations
See Appendix E
NIOSH
At concentrations above the NIOSH REL, or where there is no REL, at any detectable concentration:
APF = 10,000 Any selfcontained breathing apparatus that has a full facepiece and is operated in a pressuredemand
or other positivepressure mode
APF = 10,000 Any suppliedair respirator that has a full facepiece and is operated in a pressuredemand or other
positivepressure mode in combination with an auxiliary selfcontained positivepressure breathing apparatus
Escape:
APF = 50 Any airpurifying, fullfacepiece respirator gas mask with a chinstyle, front or backmounted organic
vapor canister
Any appropriate escapetype, selfcontained breathing apparatus
Important additional information about respirator selection
12.7.19 Fire Prevention
NO open flames, NO sparks and NO smoking.

from ILOICSC
12.7.20 Explosion Prevention
Closed system, ventilation, explosionproof electrical equipment and lighting. Do NOT use compressed air for filling,
discharging, or handling. Use nonsparking handtools. Prevent buildup of electrostatic charges e.g., by grounding.
from ILOICSC
12.7.21 Exposure Prevention
AVOID ALL CONTACT!

from ILOICSC
12.7.22 Inhalation Prevention
Use ventilation, local exhaust or breathing protection.

from ILOICSC
12.7.23 Skin Prevention
Protective gloves. Protective clothing.

from ILOICSC
12.7.24 Eye Prevention
Wear face shield or eye protection in combination with breathing protection.

from ILOICSC
12.7.25 Ingestion Prevention
Do not eat, drink, or smoke during work.

from ILOICSC
12.7.26 Protective Equipment and Clothing
Skin: Wear appropriate personal protective clothing to prevent skin contact. Eyes: Wear appropriate eye protection to
prevent eye contact. Wash skin: The worker should immediately wash the skin when it becomes contaminated.
Remove: Work clothing that becomes wet should be immediately removed due to its flammability hazardi.e. for
liquids with flash point < 100F Change: No recommendation is made specifying the need for the worker to change
clothing after the work shift. Provide: Eyewash fountains should be provided in areas where there is any possibility
that workers could be exposed to the substance; this is irrespective of the recommendation involving the wearing of
eye protection. Facilities for quickly drenching the body should be provided within the immediate work area for
emergency use where there is a possibility of exposure. [Note: It is intended that these facilities provide a sufficient
quantity or flow of water to quickly remove the substance from any body areas likely to be exposed. The actual
determination of what constitutes an adequate quick drench facility depends on the specific circumstances. In certain
instances, a deluge shower should be readily available, whereas in others, the availability of water from a sink or hose
could be considered adequate.] NIOSH, 2016
Protective clothing consisting of coveralls or other full body clothing should be worn and changed at least twice
weekly.
from HSDB
Where there is a possibility of benzene contact to eyes or skin, safety showers, eyewash fountains, and cleansing
facilities shall be installed and maintained.
NIOSH; Criteria Document: Benzene p.13 (1974) DHEW Pub. No. 74137
from HSDB
Where high vapor concn are unavoidable, forced air masks should be used. Lifeline attended by ... person outside
contaminated enclosure is mandatory. If skin contact is unavoidable, neoprene gloves must be worn.
Dreisbach, R.H. Handbook of Poisoning. 12th ed. Norwalk, CT: Appleton and Lange, 1987., p. 193
from HSDB
Hydrocarbon vapor canister, supplied air or a hose mask; hydrocarbon insoluble rubber or plastic gloves; chemical
goggles or face splash shield; hydrocarboninsoluble apron such as neoprene.
U.S. Coast Guard, Department of Transportation. CHRIS Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government
Printing Office, 19845.
from HSDB
PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be
used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits preferably disposable, one
piece & closefitting at ankles & wrists, gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns
should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or
respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide
addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside
the laboratory. /Chemical Carcinogens/
from HSDB
Performance data: For butyl rubber, natural rubber, neoprene, neoprene, neoprene/natural rubber, nitrile rubber,
polyethylene, chlorinated polyethylene, polyurethane, and polyvinyl chloride give breakthrough times less usually
significantly less than one hour reported by normally two or more testers. Vendor Recommendations: C or D ratings
from three or more apparently independent vendors.
ACGIH; Guidelines Select of Chem Protect Clothing Volume #1 Field Guide p.58 (1983)
from HSDB
Wear appropriate personal protective clothing to prevent skin contact.

from HSDB
Wear appropriate eye protection to prevent eye contact.

from HSDB
Eyewash fountains should be provided in areas where there is any possibility that workers could be exposed to the
substance; this is irrespective of the recommendation involving the wearing of eye protection.
from HSDB
Facilities for quickly drenching the body should be provided within the immediate work area for emergency use where
there is a possibility of exposure. [Note: It is intended that these facilities should provide a sufficient quantity or flow
of water to quickly remove the substance from any body areas likely to be exposed. The actual determination of what
constitutes an adequate quick drench facility depends on the specific circumstances. In certain instances, a deluge
shower should be readily available, whereas in others, the availability of water from a sink or hose could be
considered adequate.]
from HSDB
Respirator Recommendations: At concentrations above the NIOSH REL, or where there is no REL, at any detectable
concentration:
Assigned
Protection Respirator Recommendations
Factor APF
Any selfcontained breathing apparatus that has a full facepiece and is operated in a pressure
APF = 10,000
demand or other positivepressure mode.
Any suppliedair respirator that has a full facepiece and is operated in a pressuredemand or
APF = 10,000 other positivepressure mode in combination with an auxiliary selfcontained positivepressure
breathing apparatus.
from HSDB
Respirator Recommendations: Escape:

Assigned
Protection Respirator Recommendations
Factor APF
Any airpurifying, fullfacepiece respirator gas mask with a chinstyle, front or backmounted
APF = 50
organic vapor canister/Any appropriate escapetype, selfcontained breathing apparatus.
from HSDB
Eye/face protection: Face shield and safety glasses Use equipment for eye protection tested and approved under
appropriate government standards such as NIOSH US or EN 166EU.
from HSDB
Skin protection: Handle with gloves.

from HSDB
Body Protection: Complete suit protecting against chemicals. Flame retardant antistatic protective clothing. The type
of protective equipment must be selected according to the concentration and amount of the dangerous substance at
the specific workplace.
from HSDB
Respiratory protection: Where risk assessment shows airpurifying respirators are appropriate use a fullface respirator
with multipurpose combination US or type ABEK EN 14387 respirator cartridges as a backup to engineering
controls. If the respirator is the sole means of protection, use a fullface supplied air respirator. Use respirators and
components tested and approved under appropriate government standards such as NIOSH US or CEN EU.
from HSDB
12.8 Stability and Reactivity
12.8.1 Air and Water Reactions
Highly flammable. Slightly soluble in water.

12.8.2 Reactive Group
Hydrocarbons, Aromatic
12.8.3 Reactivity Alerts
Highly Flammable
12.8.4 Reactivity Profile
BENZENE reacts vigorously with allyl chloride or other alkyl halides even at 70 C in the presence of ethyl aluminum
dichloride or ethyl aluminum sesquichloride. Explosions have been reported [NFPA 491M 1991]. Ignites in contact
with powdered chromic anhydride [Mellor 11:235 194647]. Incompatible with oxidizing agents such as nitric acid.
Mixtures with bromine trifluoride, bromine pentafluoride, iodine pentafluoride, iodine heptafluoride and other
interhalogens can ignite upon heating [Bretherick 5th ed. 1995]. Benzene and cyanogen halides yield HCl as a
byproduct Hagedorn, F. H. Gelbke, and Federal Republic of Germany. 2002. Nitriles. In Ullmann's Encyclopedia of
Industrial Chemistry. WileyVCH Verlag GmbH & Co. KGaA.. The reaction of benzene and trichloroacetonitrile evolves
toxic chloroform and HCl gases. Hagedorn, F., H.P. Gelbke, and Federal Republic of Germany. 2002. Nitriles. In
Ullmann's Encyclopedia of Industrial Chemistry. WileyVCH Verlag GmbH & Co. KGaA..
12.8.5 Reactivities and Incompatibilities
Reacts violently with iodine pentafluoride.

from HSDB
Hydrogenation of benzene to cyclohexane was effected in a fixed bed reactor at 210230 deg C, but a fall in
conversion was apparent. Increasing the bed temp by 10 deg C & the hydrogen flow led to a large increase in
reaction rate which the interbed cooling coils could not handle, & an exotherm to 280 deg C developed, with a hot
spot around 600 deg C which bulged the reactor wall.
Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: ButterworthHeinemann Ltd., 1990, p. 612
from HSDB
Benzene ... ignites in contact with /iodine heptafluoride/ gas ...

from HSDB
Dioxygenyl tetrafluoroborate is a very powerful oxidant, addition of a small particle to small samples of benzene ... at
ambient temp ... /caused/ ignition.
from HSDB
... A 2% solution /dioxygen difluoride/ in hydrogen fluoride ignites solid benzene at 78 deg C.
from HSDB
Simultaneous contact of sodium peroxide with ... benzene ... causes ignition, equivalent to contact with concn
hydrogen peroxide.
from HSDB
Interaction /of uranium hexafluoride/ with benzene ... is very vigorous, with separation of carbon ...
from HSDB
Benzene ignites in contact with powdered chromic anhydride.

from HSDB
An explosion of benzene vapors & chlorine inadvertently mixed was initiated by light.
from HSDB
Reacts explosively with bromine pentafluoride, chlorine, chlorine trifluoride, diborane, nitric acid, nitryl perchlorate,
oxygen liquid, ozone, silver perchlorate.
from HSDB
Interaction of the pentafluoride & methoxide /from arsenic pentafluoride & potassium methoxide/ proceeded
smoothly in trichlorotrifluoroethane at 3040 deg C, whereas in benzene as solvent repeated explosions occurred.
from HSDB
The effects of the presence of moisture or benzene vapor in air on the spontaneously explosive reaction /of diborane/
have been studied.
from HSDB
Silver perchlorate forms solid complexes with aniline, pyridine, toluene, benzene & many other aromatic
hydrocarbons. A sample of the benzene complex exploded violently on crushing in a mortar.
from HSDB
Interaction /of nitryl perchlorate/ with benzene gave a slight explosion & flash. ...
from HSDB
The solution of permanganic acid or its explosive anhydride, dimanganese heptoxide produced by interaction of
permanganates & sulfuric acid, will explode on contact with benzene ... .
from HSDB
Largescale addition of toocold nitrating acid to benzene without agitation later caused an uncontrollably violent
reaction to occur when stirring was started. The vaporair mixture produced was ignited by interaction of benzene &
nitric acid at 100170 deg C & caused an extremely violent explosion.
from HSDB
Peroxodisulfuric acid ... /is/ a very powerful oxidant; uncontrolled contact with ... benzene ... may cause explosion.
from HSDB
Mixtures of /liquid oxygen &/ benzene are specifically described as explosive.

from HSDB
During ozonization of rubber dissolved in benzene, an explosion occurred. This seems unlikely to have been ... /due/
to formation of benzene triozonide which separates as a gelatinous precipitate after prolonged ozonization, since
the solution remained clear. A rubber ozonide may have been involved, but the benzeneoxygen system itself has
high potential for hazard.
from HSDB
Mixtures /of peroxomonosulfuric acid/ with ... benzene ... explodes.

from HSDB
Certain metal perchlorates recrystallized from benzene or ethyl alcohol can explode spontaneously.
from HSDB
Strong oxidizers, many fluorides & perchlorates, nitric acid.

from HSDB
Vigorous or incandescent reaction with hydrogen + Raney nickel above 210 deg C uranium hexafluoride, and
bromine trifluoride. Can react vigorously with oxidizing materials, such as Cl2, CrO3, oxygen, NClO4, ozone,
perchlorates, AlCl3 + FClO4, sulfuric acid + permanganates, K2O2, AgClO4 + acetic acid, N2O2.
NJ. 2004., p. 360
from HSDB
Explodes on contact with diborane, bromine pentafluoride, permanganic acid, peroxomonosulfuric acid, and
peroxodisulfuric acid. Forms sensitive, explosive mixtures with iodine pentafluoride, silver perchlorate, nitryl
perchlorate, nitric acid, liquid oxygen, ozone, arsenic pentafluoride + potassium methoxide explodes above 30 deg
C. ... Moderate explosion hazard when exposed to heat or flame.
NJ. 2004., p. 360
from HSDB
Incompatible materials: Acids, bases, halogens, strong oxidizing agents, metallic salts.
from HSDB
CHEMICAL PROFILE: Allyl chloride or other alkyl halides will react vigorously with benzene or toluene, even at minus
70C. in the presence of ethyl aluminum dichloride or ethyl aluminum sesquichloride. Explosions have been reported
NFPA 491M 1991. Benzene ignites in contact with the powdered chromic anhydride Mellor 11:235 194647.
REACTIVITY, 1999
This compound is incompatible with the following:Strong oxidizers NIOSH, 1997

Strong oxidizers, many fluorides & perchlorates, nitric acid

12.9 Transport Information
12.9.1 DOT Emergency Guidelines
/GUIDE 130: FLAMMABLE LIQUIDS NonPolar/WaterImmiscible/Noxious/ Fire or Explosion: HIGHLY FLAMMABLE:

Will be easily ignited by heat, sparks or flames. Vapors may form explosive mixtures with air. Vapors may travel to
source of ignition and flash back. Most vapors are heavier than air. They will spread along ground and collect in low or
confined areas sewers, basements, tanks. Vapor explosion hazard indoors, outdoors or in sewers. Those substances
designated with a P may polymerize explosively when heated or involved in a fire. Runoff to sewer may create fire or
explosion hazard. Containers may explode when heated. Many liquids are lighter than water.
U.S. Department of Transportation. 2012 Emergency Response Guidebook. Washington, D.C. 2012
from HSDB
/GUIDE 130: FLAMMABLE LIQUIDS NonPolar/WaterImmiscible/Noxious/ Health: May cause toxic effects if inhaled
or absorbed through skin. Inhalation or contact with material may irritate or burn skin and eyes. Fire will produce
irritating, corrosive and/or toxic gases. Vapors may cause dizziness or suffocation. Runoff from fire control or dilution
water may cause pollution.
from HSDB
/GUIDE 130: FLAMMABLE LIQUIDS NonPolar/WaterImmiscible/Noxious/ Public Safety: CALL Emergency Response
Telephone Number on Shipping Paper first. If Shipping Paper not available or no answer, refer to appropriate
telephone number listed on the inside back cover. As an immediate precautionary measure, isolate spill or leak area
for at least 50 meters 150 feet in all directions. Keep unauthorized personnel away. Stay upwind. Keep out of low
areas. Ventilate closed spaces before entering.
from HSDB
/GUIDE 130: FLAMMABLE LIQUIDS NonPolar/WaterImmiscible/Noxious/ Protective Clothing: Wear positive

pressure selfcontained breathing apparatus SCBA. Structural firefighters' protective clothing will only provide
limited protection.
from HSDB
/GUIDE 130: FLAMMABLE LIQUIDS NonPolar/WaterImmiscible/Noxious/ Evacuation: Large Spill: Consider initial
downwind evacuation for at least 300 meters 1000 feet. Fire: If tank, rail car or tank truck is involved in a fire,
ISOLATE for 800 meters 1/2 mile in all directions; also, consider initial evacuation for 800 meters 1/2 mile in all
directions.
from HSDB
/GUIDE 130: FLAMMABLE LIQUIDS NonPolar/WaterImmiscible/Noxious/ Fire: CAUTION: All these products have a
very low flash point: Use of water spray when fighting fire may be inefficient. Small Fire: Dry chemical, CO2, water
spray or regular foam. Large Fire: Water spray, fog or regular foam. Do not use straight streams. Move containers
from fire area if you can do it without risk. Fire involving Tanks or Car/Trailer Loads: Fight fire from maximum distance
or use unmanned hose holders or monitor nozzles. Cool containers with flooding quantities of water until well after
fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS
stay away from tanks engulfed in fire. For massive fire, use unmanned hose holders or monitor nozzles; if this is
impossible, withdraw from area and let fire burn.
from HSDB
/GUIDE 130: FLAMMABLE LIQUIDS NonPolar/WaterImmiscible/Noxious/ Spill or Leak: ELIMINATE all ignition
sources no smoking, flares, sparks or flames in immediate area. All equipment used when handling the product must
be grounded. Do not touch or walk through spilled material. Stop leak if you can do it without risk. Prevent entry into
waterways, sewers, basements or confined areas. A vapor suppressing foam may be used to reduce vapors. Absorb or
cover with dry earth, sand or other noncombustible material and transfer to containers. Use clean nonsparking tools
to collect absorbed material. Large Spill: Dike far ahead of liquid spill for later disposal. Water spray may reduce vapor;
but may not prevent ignition in closed spaces.
from HSDB
/GUIDE 130: FLAMMABLE LIQUIDS NonPolar/WaterImmiscible/Noxious/ First Aid: Move victim to fresh air. Call 911
or emergency medical service. Give artificial respiration if victim is not breathing. Administer oxygen if breathing is
difficult. Remove and isolate contaminated clothing and shoes. In case of contact with substance, immediately flush
skin or eyes with running water for at least 20 minutes. Wash skin with soap and water. In case of burns, immediately
cool affected skin for as long as possible with cold water. Do not remove clothing if adhering to skin. Keep victim
warm and quiet. Effects of exposure inhalation, ingestion or skin contact to substance may be delayed. Ensure that
medical personnel are aware of the materials involved and take precautions to protect themselves.
from HSDB
12.9.2 Shipment Methods and Regulations
No person may /transport,/ offer or accept a hazardous material for transportation in commerce unless that person is
registered in conformance ... and the hazardous material is properly classed, described, packaged, marked, labeled,
and in condition for shipment as required or authorized by ... /the hazardous materials regulations 49 CFR 171177./
49 CFR 171.2 (USDOT); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from,
as of February 5, 2014: http://www.ecfr.gov
from HSDB
The International Air Transport Association IATA Dangerous Goods Regulations are published by the IATA
Dangerous Goods Board pursuant to IATA Resolutions 618 and 619 and constitute a manual of industry carrier
regulations to be followed by all IATA Member airlines when transporting hazardous materials.
International Air Transport Association. Dangerous Goods Regulations. 47th Edition. Montreal, Quebec Canada. 2006., p. 148
from HSDB
The International Maritime Dangerous Goods Code lays down basic principles for transporting hazardous chemicals.
Detailed recommendations for individual substances and a number of recommendations for good practice are
included in the classes dealing with such substances. A general index of technical names has also been compiled. This
index should always be consulted when attempting to locate the appropriate procedures to be used when shipping
any substance or article.
International Maritime Organization. IMDG Code. International Maritime Dangerous Goods Code Volume 2 2006, p. 46
from HSDB
PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling,
carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed
inside strong screwcap or snaptop container that will not open when dropped & will resist attack from the
carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway
companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These
authorities should be consulted before ... material is shipped. /Chemical Carcinogens/
from HSDB
PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The
carcinogen should be enclosed in a securely sealed, watertight container primary container, which should be
enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen
secondary container. The space between primary & secondary container should be filled with absorbent material,
which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary
container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer
box. The space between the secondary container & the outer box should be filled with an appropriate quantity of
shockabsorbent material. Sender should use fastest & most secure form of transport & notify recipient of its
departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made
to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday. ... /Chemical Carcinogens/
from HSDB
12.9.3 DOT ID and Guide
1114 130
from DOT Emergency Response Guidebook, The National Institute for Occupational Safety and Health NIOS
12.9.4 DOT Label
Flammable Liquid
12.9.5 Packaging and Labelling
Do not transport with food and feedstuffs.

from ILOICSC
12.9.6 EC Classification
Symbol: F, T; R: 45461136/3848/23/24/2565; S: 5345; Note: E

from ILOICSC
12.9.7 UN Classification
UN Hazard Class: 3; UN Pack Group: II

from ILOICSC
12.9.8 Emergency Response
NFPA Code: H2; F3; R0.

from ILOICSC
12.10 Regulatory Information
12.10.1 DOT Emergency Response Guide
130 FLAMMABLE LIQUIDS NonPolar / WaterImmiscible / Noxious POTENTIAL HAZARDS FIRE OR

EXPLOSION * HIGHLY FLAMMABLE: Will be easily ignited by heat, sparks or flames. * Vapors may form explosive
mixtures with air. * Vapors may travel to source of ignition and flash back. * Most vapors are heavier than air. They will
spread along ground and collect in low or confined areas sewers, basements, tanks. * Vapor explosion hazard
indoors, outdoors or in sewers. * Those substances designated with a "P" may polymerize explosively when heated or
involved in a fire. * Runoff to sewer may create fire or explosion hazard. * Containers may explode when heated. *
Many liquids are lighter than water. HEALTH * May cause toxic effects if inhaled or absorbed through skin. *
Inhalation or contact with material may irritate or burn skin and eyes. * Fire will produce irritating, corrosive and/or
toxic gases. * Vapors may cause dizziness or suffocation. * Runoff from fire control or dilution water may cause
pollution. PUBLIC SAFETY * CALL Emergency Response Telephone Number on Shipping Paper first. If Shipping Paper
not available or no answer, refer to appropriate telephone number listed on the inside back cover. * As an immediate
precautionary measure, isolate spill or leak area for at least 50 meters 150 feet in all directions. * Keep unauthorized
personnel away. * Stay upwind. * Keep out of low areas. * Ventilate closed spaces before entering. PROTECTIVE
CLOTHING * Wear positive pressure selfcontained breathing apparatus SCBA. * Structural firefighters' protective
clothing will only provide limited protection. EVACUATION Large Spill * Consider initial downwind evacuation for at
least 300 meters 1000 feet. Fire * If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters 1/2 mile
in all directions; also, consider initial evacuation for 800 meters 1/2 mile in all directions. EMERGENCY RESPONSE
FIRE CAUTION: All these products have a very low flash point: Use of water spray when fighting fire may be
inefficient. Small Fire * Dry chemical, CO2, water spray or regular foam. Large Fire * Water spray, fog or regular
foam. * Do not use straight streams. * Move containers from fire area if you can do it without risk. Fire involving
Tanks or Car/Trailer Loads * Fight fire from maximum distance or use unmanned hose holders or monitor nozzles. *
Cool containers with flooding quantities of water until well after fire is out. * Withdraw immediately in case of rising
sound from venting safety devices or discoloration of tank. * ALWAYS stay away from tanks engulfed in fire. * For
massive fire, use unmanned hose holders or monitor nozzles; if this is impossible, withdraw from area and let fire
burn. SPILL OR LEAK * ELIMINATE all ignition sources no smoking, flares, sparks or flames in immediate area. * All
equipment used when handling the product must be grounded. * Do not touch or walk through spilled material. *
Stop leak if you can do it without risk. * Prevent entry into waterways, sewers, basements or confined areas. * A vapor
suppressing foam may be used to reduce vapors. * Absorb or cover with dry earth, sand or other noncombustible
material and transfer to containers. * Use clean nonsparking tools to collect absorbed material. Large Spill * Dike far
ahead of liquid spill for later disposal. * Water spray may reduce vapor; but may not prevent ignition in closed spaces.
FIRST AID * Move victim to fresh air. * Call 911 or emergency medical service. * Give artificial respiration if victim is
not breathing. * Administer oxygen if breathing is difficult. * Remove and isolate contaminated clothing and shoes. *
In case of contact with substance, immediately flush skin or eyes with running water for at least 20 minutes. * Wash
skin with soap and water. * In case of burns, immediately cool affected skin for as long as possible with cold water. Do
not remove clothing if adhering to skin. * Keep victim warm and quiet. * Effects of exposure inhalation, ingestion or
skin contact to substance may be delayed. * Ensure that medical personnel are aware of the materials involved and
take precautions to protect themselves.
12.10.2 Federal Drinking Water Standards
Maximum contaminant levels MCL for organic contaminants apply to community and nontransient, noncommunity
water systems: Benzene, MCL 0.005 mg/L.
40 CFR 141.61(a) (USEPA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available
from HSDB
EPA 5 ug/L
USEPA/Office of Water; FederalState Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking
Water Standards and Guidelines (11/93) To Present
from HSDB
12.10.3 State Drinking Water Standards
CA CALIFORNIA 1 ug/L
from HSDB
FL FLORIDA 1 ug/L
from HSDB
NJ NEW JERSEY 1 ug/L

from HSDB
12.10.4 State Drinking Water Guidelines
AZ ARIZONA 1.3 ug/L

from HSDB
CT CONNECTICUT 1 ug/L
from HSDB
ME MAINE 6 ug/L
from HSDB
MN MINNESOTA 3 ug/L
from HSDB
12.10.5 Clean Water Act Requirements
Toxic pollutant designated pursuant to section 307a1 of the Federal Water Pollution Control Act and is subject to
effluent limitations.
40 CFR 401.15 (USEPA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from,
as of January 28, 2014: http://www.ecfr.gov/cgibin/ECFR?page=browse
from HSDB
Benzene is designated as a hazardous substance under section 311b2A of the Federal Water Pollution Control Act
and further regulated by the Clean Water Act Amendments of 1977 and 1978. These regulations apply to discharges
of this substance. This designation includes any isomers and hydrates, as well as any solutions and mixtures
containing this substance.
from HSDB
12.10.6 CERCLA Reportable Quantities
Persons in charge of vessels or facilities are required to notify the National Response Center NRC immediately, when
there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable
quantity of 10 lb or 4.54 kg. The toll free number of the NRC is 800 4248802. The rule for determining when
notification is required is stated in 40 CFR 302.4 section IV.D.3.b.
from HSDB
12.10.7 RCRA Requirements
D018; A solid waste containing benzene may or may not become characterized as a hazardous waste when subjected
to the Toxicity Characteristic Leaching Procedure listed in 40 CFR 261.24, and if so characterized, must be managed as
a hazardous waste.
from HSDB
F005; When benzene is a spent solvent, it is classified as a hazardous waste from a nonspecific source F005, as stated
in 40 CFR 261.31, and must be managed according to State and/or Federal hazardous waste regulations.
from HSDB
U019; As stipulated in 40 CFR 261.33, when benzene, as a commercial chemical product or manufacturing chemical
intermediate or an offspecification commercial chemical product or a manufacturing chemical intermediate, becomes
a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a
hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into
water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from
hazardous waste regulations 40 CFR 261.5.
from HSDB
12.10.8 FDA Requirements
Benzene is an indirect food additive for use only as a component of adhesives.

21 CFR 175.105 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available
from HSDB
12.11 Other Safety Information
12.11.1 Other Hazardous Reactions
May accumulate static electricity

from HSDB
13 Toxicity
13.1 Toxicological Information
13.1.1 NIOSH Toxicity Data
Download
1 to 6 of 280 View More
Measurement Count
Skin and Eye Irritation 5
Mutation Data 105
Reproductive Effects Data 30
Tumorigenic Data 25
Acute Toxicity Data 55
Other Multiple Dose Data 60
Download
Measurement Count
Skin and Eye Irritation 2
Tumorigenic Data 1
Acute Toxicity Data 9
Other Multiple Dose Data 4
13.1.2 Carcinogen
NTP: Known to be a human carcinogen, EPA: Known human carcinogen, IARC: Carcinogenic to humans
Classification of carcinogenicity: 1 evidence in humans: sufficient; 2 evidence in animals: sufficient; Overall summary
evaluation of carcinogenic risk to humans is group 1: The chemical is carcinogenic to humans. /From table/
http://monographs.iarc.fr/ENG/Classification/index.php , p. S7 120 (1987)
from HSDB
A1; Confirmed human carcinogen.

from HSDB
Cancer Classification: Carcinogenic to Humans

USEPA Office of Pesticide Programs, Health Effects Division, Science Information Management Branch: "Chemicals Evaluated for
Carcinogenic Potential" (April 2006)
from HSDB
WEIGHTOFEVIDENCE CHARACTERIZATION: Benzene is classified as a "known" human carcinogen Category A

under the Risk Assessment Guidelines of 1986. Under the proposed revised Carcinogen Risk Asessment Guidelines
USEPA, 1996, benzene is characterized as a known human carcinogen for all routes of exposure based upon
convincing human evidence as well as supporting evidence from animal studies. Epidemiologic studies and case
studies provide clear evidence of a causal association between exposure to benzene and acute nonlymphocytic
leukemia and also suggest evidence for chronic nonlymphocytic leukemia and chronic lymphocytic leukemia. Other
neoplastic conditions that are associated with an increased risk in humans are hematologic neoplasms, blood
disorders such as preleukemia and aplastic anemia, Hodgkin's lymphoma, and myelodysplastic syndrome. These
human data are supported by animal studies. The experimental animal data add to the argument that exposure to
benzene increases the risk of cancer in multiple species at multiple organ sites hematopoietic, oral and nasal, liver,
forestomach, preputial gland, lung, ovary, and mammary gland. It is likely that these responses are due to
interactions of the metabolites of benzene with DNA ... Recent evidence supports the viewpoint that there are likely
multiple mechanistic pathways leading to cancer and, in particular, to leukemogenesis from exposure to benzene.
HUMAN CARCINOGENICITY DATA: Benzene is a known human carcinogen based upon evidence presented in
numerous occupational epidemiological studies. Significantly increased risks of leukemia, chiefly acute myelogenous
leukemia, have been reported in benzeneexposed workers in the chemical industry, shoemaking and oil refineries.
ANIMAL CARCINOGENICITY DATA:... many experimental animal studies, both inhalation and oral, also support the
evidence that exposure to benzene increases the risk of cancer in multiple organ systems, including the hematopoietic
system, oral and nasal cavities, liver, forestomach, preputial gland, lung, ovary, and mammary gland ....
U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS). Summary on Benzene (71432). Available from,
as of February 21, 2014: http://www.epa.gov/IRIS/subst/0276.htm
from HSDB
Benzene: known to be a human carcinogen. Carcinogenicity: Benzene is known to be a human carcinogen based on
sufficient evidence of carcinogenicity from studies in humans.
DHHS/National Toxicology Program; Twelfth Report on Carcinogens: Benzene (71432) (2011). Available from, as of February 21,
2014: http://ntp.niehs.nih.gov/ntp/roc/twelfth/profiles/Benzene.pdf
from HSDB
EPAA; K, IARC1, NIOSHCa, NTPK, OSHACa, TLVA1

13.1.3 Health Effects
IrritationEye, Nose, Throat, SkinMild HE16 Narcosis HE8

13.1.4 Exposure Routes
The substance can be absorbed into the body by inhalation, through the skin and by ingestion.
from ILOICSC
inhalation, skin absorption, ingestion, skin and/or eye contact

13.1.5 Symptoms
irritation eyes, skin, nose, respiratory system; dizziness; headache, nausea, staggered gait; anorexia, lassitude
weakness, exhaustion; dermatitis; bone marrow depression; [potential occupational carcinogen]
13.1.6 Inhalation Symptoms
Dizziness. Drowsiness. Headache. Nausea. Shortness of breath. Convulsions. Unconsciousness.

from ILOICSC
13.1.7 Skin Symptoms
MAY BE ABSORBED! Dry skin. Redness. Pain. Further see Inhalation.

from ILOICSC
13.1.8 Eye Symptoms
Redness. Pain.
from ILOICSC
13.1.9 Ingestion Symptoms
Abdominal pain. Sore throat. Vomiting. Further see Inhalation.

from ILOICSC
13.1.10 Target Organs
Hematological Blood Forming, Immunological Immune System, Neurological Nervous System

Respiratory system, eyes, skin

Eyes, skin, respiratory system, blood, central nervous system, bone marrow
13.1.11 Cancer Sites
[leukemia]
13.1.12 Acute Toxicity Link
Chemical: BENZENE
from USGS Columbia Environmental Research Center
13.1.13 Acute Effects
Coexposure to benzene with ethanol e.g., alcoholic beverages can increase benzene toxicity in humans.
Neurological symptoms of inhalation exposure to benzene include drowsiness, dizziness, headaches, and
unconsciousness in humans. Ingestion of large amounts of benzene may result in vomiting, dizziness, and convulsions
in humans.
Exposure to liquid and vapor may irritate the skin, eyes, and upper respiratory tract in humans. Redness and blisters
may result from dermal exposure to benzene.
Animal studies show neurologic, immunologic, and hematologic effects from inhalation and oral exposure to benzene.
Tests involving acute exposure of rats, mice, rabbits, and guinea pigs have demonstrated benzene to have low acute
toxicity from inhalation, moderate acute toxicity from ingestion, and low or moderate acute toxicity from dermal
exposure.
The reference concentration for benzene is 0.03 mg/m3 based on hematological effects in humans. The RfC is an
estimate with uncertainty spanning perhaps an order of magnitude of a continuous inhalation exposure to the
human population including sensitive groups that is likely to be without appreciable risk deleterious noncancer
effects over a lifetime.
from EPA Air Toxics
13.1.14 Chronic Effects
Chronic inhalation of certain levels of benzene causes disorders in the blood in humans. Benzene specifically affects
bone marrow the tissues that produce blood cells. Aplastic anemia a risk factor for acute nonlymphocytic leukemia,
excessive bleeding, and damage to the immune system by changes in blood levels of antibodies and loss of white
blood cells may develop.
In animals, chronic inhalation and oral exposure to benzene produces the same effects as seen in humans.
Benzene causes both structural and numerical chromosomal aberrations in humans.
EPA has established an oral Reference Dose RfD for benzene of 0.004 milligrams per kilogram per day mg/kg/d
based on hematological effects in humans. The RfD is an estimate with uncertainty spanning perhaps an order of
magnitude of a daily oral exposure to the human population including sensitive subgroups that is likely to be
without appreciable risk of deleterious noncancer effects during a lifetime. It is not a direct estimator of risk, but
rather a reference point to gauge the potential for effects. At exposures increasingly greater than the RfD, the
potential for adverse health effects increases. Lifetime exposure above the RfD does not imply that an adverse health
effect would necessarily occur.
EPA has established a Reference Concentration RfC of 0.03 milligrams per cubic meter 0.03 mg/m3 for benzene
based on hematological effects in humans. The RfC is an inhalation exposure concentration at or below which adverse
health effects are not likely to occur. It is not a direct estimator of risk, but rather a reference point to gauge the
potential for effects. At lifetime exposures increasingly greater than the reference exposure level, the potential for
adverse health effects increases.
from EPA Air Toxics
13.1.15 Cancer Risk
Increased incidence of leukemia cancer of the tissues that form white blood cells has been observed in humans
occupationally exposed to benzene.
EPA has classified benzene as a Group A, known human carcinogen.
EPA uses mathematical models, based on human and animal studies,to estimate the probability of a person
developing cancer from breathing air containing a specified concentration of a chemical. EPA calculated a range of 2.2
x 106 to 7.8 x 106 as the increase in the lifetime risk of an individual who is continuously exposed to 1 g/m3 of
benzene in the air over their lifetime.
EPA estimates that, if an individual were to continuously breathe the air containing benzene at an average of 0.13 to
0.45 g/m3 1.3x104 to 4.5x4mg/m3 over his or her entire lifetime, that person would theoretically have no more
than a oneinamillion increased chance of developing cancer as a direct result of continuously breathing air
containing this chemical. Similarly, EPA estimates
https://pubchem.ncbi.nlm.nih.gov/compound/benzene#section=Top that continuously breathing air containing 1.3 to 4.5 g/m3 1.3x10385/149
containing this chemical. Similarly, EPA estimates that continuously breathing air containing 1.3 to 4.5 g/m3 1.3x103
to 4.5x103 mg/m3 would result in not greater than a oneinahundred thousand increased chance of developing
cancer, and air containing 13 to 45 g/m3 1.3 x 102 to 4.5 x 102 mg/m3 would result in not greater than a onein
ten thousand increased chance of developing cancer. For a detailed discussion of confidence in the potency
estimates, please see IRIS.
EPA has calculated an oral cancer slope factor ranging from 1.5 x 102 to 5.5 x 102mg/kg/d1 that is an extrapolation
from inhalation doseresponse data.
from EPA Air Toxics
13.1.16 Reproductive and Developmental Effects
There is some evidence from human epidemiological studies of reproductive and developmental toxicity of benzene,
however the data do not provide conclusive evidence of a link between exposure and effect 4. Animal studies have
provided limited evidence that exposure to benzene may affect reproductive organs, however these effects were only
observed at exposure levels over the maximum tolerated dose .
Adverse effects on the fetus, including low birth weight, delayed bone formation, and bone marrow damage, have
been observed where pregnant animals were exposed to benzene by inhalation.
from EPA Air Toxics
13.1.17 Interactions
Dimethyl sulfoxide DMSO enhanced the hypertaurinuria produced by benzene, chlorobenzene, and toluene in rats.
Undiluted DMSO was more effective than DMSO diluted with water in potentiating the toxicity of benzene in both
rats and mice. Supernatants 9000g prepared from livers of rats treated with DMSO 24 hours earlier metabolized
more benzene than those from control rats. Abstract: PubMed
Kocsis JJ et al; Science 160: 427 (1968)
from HSDB
Benzene & ethanol induced a common cytochrome P450 species in rabbit liver specifically effective in hydroxyl
radicalmediated oxygenation of ethanol. Benzene oxidation by the benzeneinducible form of cytochrome P450 was
almost completely inhibited by catalase, superoxide dismutase, DMSO, & mannitol.
IngelmanSundberg M et al; Dev Biiochem 23 (Iss Cytochrome P450, Biochem Biophys Environ Implic): 1926 (1982)
from HSDB
Simultaneous treatments with both benzene and toluene, or benzene and piperonyl butoxide, increased the excretion
of unchanged benzene in the expired air. These compounds apparently act by inhibiting benzene metabolism.
USEPA; ECAO Atlas Document: Benzene IV12 (1980)
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Toluene, Aroclor 1254, phenobarbital, acetone, and ethanol are known to alter the metabolism and toxicity of
benzene.
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SKF525A inhibited benzene metabolism in the rat. Injection of 80 mg/kg of SKF525A in rats resulted in a depression
of phenol excretion. It also prolonged phenol excretion and interfered in the conversion of benzene to glucuronides
and free phenols.
from HSDB
Carbon monoxide, aniline, aminopyrine, cytochrome C, and metyrapone inhibited benzene metabolism in vitro by
mouse liver microsomes.
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The mutual metabolic suppression between benzene and toluene was studied. The subjects, 190 male Chinese
workers employed in shoe manufacturing, printing, audio equipment manufacture, and automobile industries, were
divided into four groups based on occupational exposure: 65 were exposed to benzene, 35 to toluene, 55 to both
compounds, and 35 served as comparisons. The arithmetic mean exposure level of benzene was 31.9 and of toluene
44.7 ppm. The mixture contained benzene at 17.9 + 29.3 and toluene at 20.5 + 25.8 ppm. The exposure levels were
measured using individual diffusive samplers. The geometric mean levels of the metabolites, phenol, catechol,
hydroquinone, hippuric acid, and ocresol, in unexposed workers were 6.9, 9.4, 4.8, 72.5, and 0.066 mg/l, respectively.
Values corrected for creatinine and specific gravity were different from the values cited above. Multiple correlation
coefficients for benzene exposure versus its three metabolites were for phenol, 0.740; for catechol, 0.629; and for
hydroquinone, 0.762. Multiple correlation coefficients for toluene and its two metabolites were 0.649 for hippuric acid
and 0.583 for ocresol. The slopes of regression lines for the exposure to benzene in the presence of toluene were less
than half of those obtained when the workers were exposed to benzene alone; however, the regression lines for
benzene in mixture versus catechol were out 80% of higher than the lines observed with benzene as the sole
pollutant. The regression lines for toluene in the mixture and excretion level of hippuric acid and hydroquinone
showed reduced metabolic conversion compared to when exposure was limited to toluene alone.
Inove O et al; Internat Arch Occupat Environ Health 60 (1): 1520 (1988)
from HSDB
Hydroquinone HQ is a metabolite of benzene, and in combination with phenol PHE, reproduces benzene
myelotoxicity. HQ readily oxidizes to 1,4benzoquinone 1,4BQ followed by the reductive addition of glutathione
GSH. Subsequent cycles of oxidation and GSH addition give rise to a variety of mono, and multiGSH substituted
conjugates. Following administration of PHE/HQ 1.1 mmol/kg/0.9 mmol/kg, ip to male SpragueDawley SD rats, 2
glutathionSylHQ [GSHQ], 2,5bisglutathionSylHQ [2,5GSHQ], 2,6bisglutathionSylHQ [2,6GSHQ], and
2,3,5trisglutathionSylHQ [2,3,5GSHQ] were all identified in bone marrow. 2CysteinSylglycineHQ [2
CysGlyHQ], 2cysteinSylHQ [2CysHQ], and 2NacetylcysteinSylHQ [2NACysHQ] were also found in the
bone marrow of PHE/HQ and benzene treated rats and mice, indicating the presence of an active mercapturic acid
pathway within bone marrow. Moreover, 2,6GSHQ and 2,3,5GSHQ were hematotoxic when administered to rats.
All of the HQGSH conjugates retain the ability to redox cycle and generate reactive oxygen species ROS, and to
arylate target proteins. Recent in vitro and in vivo studies in our laboratory revealed lysine and arginine residues as
primary targets of 1,4BQ, GSHQ and 2NACysHQ adduction. In contrast 1,4BQadduction of cysteine residues may
be a transient interaction, where physiological conditions dictate adduct stability. The generation of ROS and
alkylation of proteins may both contribute to benzenemediated myelotoxicity, and the two processes may be inter
dependent. However, the precise molecular mechanism by which benzene and HQGSH conjugates induce
hematotoxicity remains to be determined. Within 18h of administration of PHE/HQ to SD rats a significant decrease in
blood lymphocyte count was observed. At this early time point, erythrocyte counts and hemoglobin concentrations
remained within the normal range. Concomitant with the decrease in lymphocyte count, western blot analysis of bone
marrow lysate, using HQGSH and 4hydroxy2nonenal 4HNE specific antibodies, revealed the presence of HQ
GSH and 4HNEderived protein adducts. Identification of these adducts is required before the functional significance
of such protein modifications can be determined.[Lau SS et al; Chem Biol Interact. 184 12: 2127 2010] Full text:
PMC2846198 Abstract: PubMed
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Benzene is a frequently used industrial solvent. Its toxic manifestations could be modified by sex hormones, but
mechanisms of their action are poorly understood. We have examined the influence of progesterone on lipid
peroxidation malondialdehyde, reduced glutathione GSH, and cytochrome P450 2E1 CYP2E1 in the liver and
kidneys of female rats. Progesterone applied to benzenetreated rats inhibited the formation of reactive oxygen
species ROS, but in ovariectomised benzenetreated rats it significantly increased GSH in the liver. No improvement
in CYP2E1 activity was observed in progesterone treated rats. Our results evidence that progesterone changes
benzene toxicity generation of ROS, oxidative stress. However, the probable antioxidative effect of progesterone
needs to be confirmed by further studies. Abstract: PubMed
Verma Y, Rana SV.; Arh Hig Rada Toksikol. 59 (1):19 (2008)
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The presented study investigates the protective role of zinc Zn and selenium Se in attenuating benzeneinduced
toxicity in rats. Male SpragueDawley rats were injected with benzene 0.5 mL/kg body weight ip and received a diet
supplement containing Zn and Se. Several hematological and biochemical parameters representing antioxidant
status were estimated. Histopathological examinations were performed. Results showed that food intake and body
weight gain of benzeneinjected rats were significantly lower than that of the control rats. Benzeneinjected rats
showed increased plasma malondialdehyde MDA and decreased activity of: glutathione peroxidase GSHPx,
catalase, superoxide dismutase SOD enzymes, as well as reduced glutathione GSH when compared to the control
group. Histopathological investigations revealed structural changes in benzeneinjected rats' liver. Supplementation
with Zn and Se resulted in a significant decrease in MDA, elevation in GSH, GSHPx, SOD and catalase levels. This
study shows that Zn and Se supplementation can improve the activity of antioxidant enzymes in rats and decrease the
histological anomalies induced by benzene toxicity as well. Abstract: PubMed
Ibrahim KS et al; Toxicol Ind Health. 27 (6): 53745 (2011)
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Carbon nanotubes CNTs have been synthesized and produced on large scale for their wide application. They have
high absorption ability to organic contaminants such as benzene and can form CNTsbenzene combination with
benzene. In this article, the acute pulmonary toxicity, induced by multiwall carbon nanotubes MWCNTs, benzene,
and their combination, was studied by administrating the three test materials into mice lungs via intratracheal
instillation. The biochemical parameters in bronchoalveolar lavage fluid BALF and pathological lesions in lungs were
used as endpoints to evaluate the pulmonary toxicity of the three test materials at 3day and 7day postexposure,
respectively. After the mice were intratracheally instilled with MWCNTs, benzene and MWCNTsbenzene combination
at doses of 6.67 mg/kg, 2.67 mg/kg, and 9.34 mg/kg containing 6.67 mg/kg MWCNTs and 2.67 mg/kg benzene, the
total protein, alkaline phosphatase ALP, acid phosphatase ACP, and lactate dehydrogenase LDH in BALF and
pathological lesions in lungs were examined. At 3day postexposure, MWCNTs induced obvious pulmonary toxicity
and benzene only induced slight pulmonary toxicity, whereas their combination induced very severe pulmonary
toxicity. At 7day postexposure, MWCNTs and benzene did not induce pulmonary toxicity individually, whereas their
combination still induced severe pulmonary toxicity. These data indicated that, at the instilled doses in this
experiment, the MWCNTs can alone induce acute pulmonary toxicity in mice and the benzene does not induce
pulmonary toxicity, but the pulmonary toxicity of MWCNTs is enhanced after they form MWCNTsbenzene
combination with low dose of benzene. The enhanced pulmonary toxicity may be due to the change of MWCNTs
aggregation ability after benzene is adsorbed on them. Abstract: PubMed
Li YS et al; Environ Toxicol. 25 (4): 40917 (2010)
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Toluene and benzene administered concurrently were reported to have an additive effect on induction of
chromosomal aberrations. Toluene reduced the number of sister chromatid exchanges induced by benzene when
both compounds were administered intraperitoneally to DBA/2 mice and reduced the clastogenic activity of benzene
when the two compounds were simultaneously administered orally to CD1 mice, intraperitoneally to SpragueDawley
rats, or subcutaneously to NMRI mice.
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Mice were given single doses of benzene sc & its effect on 59Fe uptake was evaluated. No suppression was found
after 1 & 12 hr & also 72 hr, whereas dosedependent inhibition of 59Fe uptake was observed 24 hr & 48 hr after
treatment with 440 or 2200 mg/kg dose. Thus, the data can be interpreted to suggest that 1 benzene did not
interfere with an incorporation of iron into heme, 2 benzene interfered with proliferation of normoblasts &
pronormoblasts, & 3 benzene did not damage hemopoietic stem cells which were in the g0 state at the time of
benzene injection.
Lee EW et al; Environ Health Perspective 39: 2937 (1981)
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13.1.18 Toxicity Summary
IIDENTIFICATION AND USE: Benzene is a clear, colorless liquid with a sweet aromatic odor. It is used mainly as a
starting material in manufacturing other chemicals, including detergents, pesticides, plastics and resins, synthetic
rubber, aviation fuel, pharmaceuticals, dye, explosives, PCB gasoline, flavors and perfumes, paints and coatings, nylon
intermediates, photographic chemicals. HUMAN EXPOSURE AND TOXICITY: Immediate signs and symptoms of
exposure to benzene: People who breathe in high levels of benzene may develop drowsiness, dizziness, rapid or
irregular heartbeat, headaches, tremors, confusion unconsciousness, death. Eating foods or drinking beverages
containing high levels of benzene can cause vomiting, irritation of the stomach, dizziness, sleepiness, convulsions,
rapid or irregular heartbeat, death. Longterm a year or more exposure to benzene causes harmful effects on the
bone marrow, resulting in anemia and excessive bleeding. It can also affect the immune system, increasing the chance
for infection. Some women who breathed high levels of benzene for many months had irregular menstrual periods
and a decrease in the size of their ovaries. Acute deaths from benzene exposure at high concentrations have been due
to ventricular fibrillation caused by exertion and release of epinephrine. Benzene causes cancer in humans. A
retrospective cohort study was conducted in 233 benzene factories and 83 control factories in 12 cities in China. The
benzene cohort and the control cohort consisted of 28,460 benzene exposed workers and 28,257 control workers. The
leukemia mortality rate was 14/100,000 personyears in the benzene cohort and 2/100,000 personyears in the control
cohort. Most 76.6% cases of benzene leukemia were of the acute type. The mortality due to benzene leukemia was
high in organic synthesis plants followed by painting and rubber synthesis industries. The concentration of benzene to
which patients with a leukemia were exposed ranged from 10 to 1000 mg/cu m mostly from 50 to 500 mg/cu m.
Benzene is genotoxic in humans: a significantly increased frequency of chromatid and isochromatid breaks in the
cultured lymphocytes of exposed workers has been reported, as well as a significant increase of peripheral blood
lymphocyte chromosomal aberrations. Metabolic activation of benzene by rat liver microsomes induced sister
chromatid exchanges and cell division delays in cultured human lymphocytes. Occupational exposure to benzene may
occur through inhalation and dermal contact. The general population may be exposed to benzene via inhalation of
ambient air, ingestion of food and drinking water, and dermal contact with consumer products containing benzene.
ANIMAL TOXICITY STUDIES: Experimental animal studies, both inhalation and oral, also support the evidence that
exposure to benzene increases the risk of cancer in multiple organ systems, including the hematopoietic system, oral
and nasal cavities, liver, forestomach, preputial gland, lung, ovary, and mammary gland. Rats exposed to 3,5268,224
ppm of benzene in a closed chamber for 15 minutes exhibited an increased number of ectopic ventricular beats. In
developmental study, rats exposed to 10, 50, or 500 ppm 32, 160 & 1600 mg/cu m of benzene for 7 hr/day had low
incidence of brain and skeletal defects. Rats exposed continuously to 209.7 ppm for 10 days prior to breeding showed
a complete absence of pregnancy. 1/10 rats exposed to 19.8 ppm had resorbed embryos. Genotoxicity studies have
demonstrated the induction of chromosomal aberrations in bonemarrow cells from mice, rats, and rabbits treated
with single or multiple daily doses of benzene ranging from about 0.2 to 2.0 mL/kg per day given either sc or ip. The
major metabolites of benzene are phenol, hydroquinone, and catechol. The route of exposure has little effect on the
subsequent metabolism of benzene to hemotoxic metabolites. ECOTOXICITY STUDIES: Young Coho salmon mortality
was 12/20 at 50 ppm after 24 hr up to 96 hr and 30/30 at 100 ppm after 24 hr in artificial seawater at 8 deg C. Herring
and anchovy larvae studies showed that 3545 ppm caused delay in development of eggs and produced abnormal
larvae; 1035 ppm caused delay in development of larvae, decrease in feeding and growth, and increase in respiration.
Blue crab juveniles when exposed to sublethal concentrations of benzene 0.1 or 5.0 ppm in a static system showed
an increase in the time needed to complete a molt cycle 50 days in case of benzeneexposed crab, as compared to
33 days for controls, a slower rate of growth of regenerating limb buds, and a depressed activity of ATPase in
mitochrondria. Oxygen consumption by the crab decreased from exposure to 1.0 ppm benzene.
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13.1.19 Antidote and Emergency Treatment
Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start
artificial respiration, preferably with a demandvalve resuscitator, bagvalvemask device, or pocket mask, as trained.
Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If
vomiting occurs, lean patient forward or place on left side headdown position, if possible to maintain an open
airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention.
/Benzene and Related Compounds/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby,
St. Louis, MO 2005, p. 2134
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Basic treatment: Establish a patent airway oropharyngeal or nasopharyngeal airway, if needed. Suction if necessary.
Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather
mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if
necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water.
Irrigate each eye continuously with 0.9% saline NS during transport ... . Do not use emetics. For ingestion, rinse
mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex,
and does not drool. Administer activated charcoal ... . /Benzene and Related Compounds/
St. Louis, MO 2005, p. 2134
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Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is
unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positivepressure ventilation techniques
with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider
administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat
arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline
NS or lactated Ringer's LR if signs of hypovolemia are present. For hypotension with signs of hypovolemia,
administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use
proparacaine hydrochloride to assist eye irrigation ... . /Benzene and related Compounds/
St. Louis, MO 2005, p. 214
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Emergency and supportive measures. 1. Maintain an open airway and assist ventilation if necessary. 2. Treat coma,
seizures, arrhythmias, and other complications is they occur. 3. Be cautious with the use of any betaadrenergic agents
eg, epinephrine, albuterol because of the possibility of dyshythmias due to myocardial sensitization. 4. Monitor vital
signs and ECG for 1224 hours after significant exposure.
OLSON, K.R. (Ed). Poisoning and Drug Overdose, Sixth Edition. McGrawHill, New York, NY 2012, p. 140
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Decontamination. 1. Inhalation. Immediately move the victim to fresh air and administer oxygen if available. 2. Skin
and eyes. remove clothing and wash the skin; irrigate exposed eyes with copious amounts of water or saline. 3.
Ingestion. Administer activated charcoal orally if conditions are appropriate. Consider gastric aspiration with a small
flexible tube if the ingestion was large eg, > 150200 mL and occurred within the previous 3060 minutes.
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Enhanced elimination. Dialysis and hemoperfusion are not effective.

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13.1.20 Medical Surveillance
...trans, transmuconic acid appeared to be the most reliable of benzene metabolites to employ for lowlevel benzene
exposure monitoring between 0.25 and 3.5 ppm.
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PRECAUTIONS FOR "CARCINOGENS": ... In relation specifically to cancer hazards, there are at present no health
monitoring methods that may ensure the early detection of preneoplastic lesions or lesions which may preclude them.
Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc
decisions should be taken concerning additional tests that might become useful or mandatory. /Chemical
Carcinogens/
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13.1.21 Human Toxicity Excerpts
/SIGNS AND SYMPTOMS/ Direct exposure of the eyes, skin, or lungs to benzene can cause tissue injury and irritation.
from HSDB
/SIGNS AND SYMPTOMS/ Immediate signs and symptoms of exposure to benzene: People who breathe in high levels
of benzene may develop the following signs and symptoms within minutes to several
hours:Drowsiness,Dizziness,Rapid or irregular heartbeat, Headaches,Tremors,Confusion Unconsciousness,Death at
very high levels. Eating foods or drinking beverages containing high levels of benzene can cause the following
symptoms within minutes to several hours: Vomiting, Irritation of the stomach,Dizziness,Sleepiness,Convulsions,Rapid
or irregular heartbeat,Death at very high levels.
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/SIGNS AND SYMPTOMS/ Longterm health effects of exposure to benzene: The major effect of benzene from long
term exposure is on the blood. Longterm exposure means exposure of a year or more. Benzene causes harmful
effects on the bone marrow and can cause a decrease in red blood cells, leading to anemia. It can also cause excessive
bleeding and can affect the immune system, increasing the chance for infection. Some women who breathed high
levels of benzene for many months had irregular menstrual periods and a decrease in the size of their ovaries. It is not
known whether benzene exposure affects the developing fetus in pregnant women or fertility in men. Animal studies
have shown low birth weights, delayed bone formation, and bone marrow damage when pregnant animals breathed
benzene. The Department of Health and Human Services DHHS has determined that benzene causes cancer in
humans. Longterm exposure to high levels of benzene in the air can cause leukemia, cancer of the bloodforming
organs.
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/SIGNS AND SYMPTOMS/ Benzene benzol ... has specific toxic effect on blood formation, causing aplastic anemia &
tendency to hemorrhage. Occasionally hemorrhages in retina & in conjunctiva are found in systemic poisoning by
benzene. In rare instances neuroretinal edema & papilledema have been described accompanying retinal
hemorrhages. It has not been established that benzene can induce retrobulbar neuritis or optic neuritis ...
Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 140
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/SIGNS AND SYMPTOMS/ Numerous earlier studies of benzeneexposed workers demonstrated that chronic exposure
to benzene air concentrations of 10 ppm or more resulted in adverse hematological effects, which increased in
severity with increasing benzene exposure levels... Several more recent epidemiological studies have demonstrated
hematological effects including significant reductions in WBC, RBC, and platelet counts in workers chronically
exposed to benzene levels below 10 ppm, and even as low as 1 ppm or less.
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/SIGNS AND SYMPTOMS/ Chronic benzene toxicity is expressed as bone marrow depression resulting in leucopenia,
anemia, or thrombocytopenia leukemogenic action. With continued exposure the disease progresses to
pancytopenia resulting from bone marrow aplasia. Evidence has accumulated implicating benzene in the etiology of
leukemias in workers in industries where benzene was heavily used. It has been suggested that leukemia is as frequent
a cause of death from chronic benzene exposure as is aplastic anemia. Abstract: PubMed
Snyder R et al; Life Sciences 21 (12): 170922 (1977)
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/SIGNS AND SYMPTOMS/ An acute hemorrhagic pneumonitis is highly likely if ... aspirated into lung.
III398
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/SIGNS AND SYMPTOMS/ Single exposures to concentrations of 66,000 mg/cu m 20,000 ppm commercial benzene
have been reported to be fatal in man within 510 minutes. At lower levels, loss of consciousness, irregular heartbeat,
dizziness, headache and nausea are observed.
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/SIGNS AND SYMPTOMS/ Nasal irritation and sore throat were reported by male and female workers exposed to 33
and 59 ppm benzene, respectively, for more than 1 year.
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/SIGNS AND SYMPTOMS/ If a person vomits because of swallowing foods or beverages containing benzene, the
vomit could be sucked into the lungs and cause breathing problems and coughing.
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/CASE REPORTS/ After a fatal occupational exposure to benzene vapors on a chemical cargo ship for only minutes,
autopsy reports on three victims revealed hemorrhagic, edematous lungs. Acute granular tracheitis, laryngitis,
bronchitis, and massive hemorrhages of the lungs were observed at autopsy of an 18yearold male who died of
benzene poisoning after intentional inhalation of benzene. Similarly, acute pulmonary edema was found during the
autopsy of a 16yearold who died after sniffing glue containing benzene.
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/CASE REPORTS/ Many acute deaths /from benzene exposure at high concn have been/ ... due to ventricular
fibrillation ... /caused by exertion/ & release of epinephrine. This was probably the mechanism involved in the death of
workers in tank cars which had contained benzene. Frequently, the man who went into the tank car to carry out an
unconscious worker died during the effort of lifting the unconscious man up the ladder.
Thienes, C., and T.J. Haley. Clinical Toxicology. 5th ed. Philadelphia: Lea and Febiger, 1972., p. 124
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/CASE REPORTS/ Many cases of acute leukemia developing as terminal stage of aplastic anemia resulting from
exposure to benzene may have been missed because bone marrow puncture was not performed. Benzene leukemia is
acute stem cell or myeloblastic leukemia, sometimes aleukemia. There may be a latent period extending over several
years between cessation of exposure with more or less pronounced anemia, & the onset of leukemia. Abstract:
PubMed
Vigliani EC, Forni A; Environ Res 11 (1): 1227 (1976)
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/CASE REPORTS/ Italian shoemakers exposed to 200500 ppm benzene in inks and glues showed an incidence of
leukemia of 1 per 1,000. Abstract: PubMed
Vigliani EC; Ann NY Acad Sci 271: 143 (1976)
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/CASE REPORTS/ Three cases of chronic leukemia were presented which had a history of chronic benzene exposure.
These three patients were part of a larger group of 58 leukemia patients with benzene exposure histories. Case 1
presented at age 43 due to cardiac complaints. The patient owned a printing shop at which he mixed pigmented dyes
with solutions of toluene or methyl alcohol ketone. The individual had a practice of sniffing the solutions as control
measure. The toluene solution on analysis was shown to contain 2.8% benzene 95.3% toluene. Blood and bone
marrow examination revealed chronic lymphatic leukemia. Case 2 was a 51 year old man with pain in the right
quadrant. This individual had owned a small plastics facility between 1955 and 1965 where he was intermittently
exposed to thinners containing 27.3% benzene. Subsequent exposure included cleaning solutions without benzene.
He was also diagnosed with chronic lymphatic leukemia. The third case was a 50 year old manager of a plastic facility
who was diabetic for 15 years and was hospitalized due to recurrent gluteal and inguinal furunculosis during the last 3
years. He had been heavily exposed to benzene between 1957 and 1965. He admitted having removed the dirt from
his hands using thinners containing benzene. Hairy cell leukemia was diagnosed. The data suggests that differences in
distribution of acute or chronic leukemias in chronic benzene exposure may be related to exposure levels, mode of
exposure, or exposure to benzene homologs or other chemicals.
Askoy M; Brit J Haematol 66 (2): 20911 (1987)
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/CASE REPORTS/ The case of a 55 year old male with hairy cell leukemia associated with chronic exposure to benzene
in an occupational setting was described. The subject had been employed as a coach paint sprayer for over 25 years
at the time of diagnosis. When that patient was questioned, it was admitted that at the job site he did not usually take
the normal protective measures to prevent exposure to the chemicals in the paints. The /investigators noted/ that
spray painting is the one of the occupations which can involve exposure to benzene, due to the use of benzene
containing solvents. The /researchers/ concluded that since three other cases of chronic leukemia have been
previously associated with exposure to benzene, more retrospective demographic studies which take occupational
exposures into account confirm the possible link between chronic benzene toxicity and leukemia, particularly the very
rare hairy cell leukemia.
Ng JP et al; Brit J Haematol 67 (1): 116 (1987)
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/CASE REPORTS/ Fifteen male workers were exposed to benzene vapors >60 ppm over several days during the
removal of residual fuel from shipyard fuel tanks. Exposures to benzene range from 1 day to 3 weeks mean of 5
days, 2.58 hours/day mean of 5.5 hours. Workers with more than 2 days 16 hours exposure reported mucous
membrane irritation 80%, and skin irritation 13% after exposure to the vapor.
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/EPIDEMIOLOGY STUDIES/ An epidemiological study implicating benzene as a leukemogen acute myelocytic

leukemia followed 748 white males exposed to benzene in the manufacture of a rubber product from 19401949. A
statistically significant p < or = 0.002 excess of leukemia was found when compared against two control populations.
There was a 5 fold excessive risk of all leukemias and a 10 fold excessive risk of myelocytic and monocytic leukemias
combined.
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/EPIDEMIOLOGY STUDIES/ /A subset of 292 men of the 594 in the benzene exposure of Dow cohort who were still
employed in 1967/ had an examination of the health status /evaluation/ carried out between 19671974 and
compared to a control population selected from employees not exposed to benzene, using a matched pair design
matched for age, cigarette smoking habits and length of employment. No clinically significant differences were
reported although slight decr in total bilirubin levels and red blood cell counts were noted. Abstract: PubMed
Towsent et al; J Occup Med 20: 5438 (1978)
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/EPIDEMIOLOGY STUDIES/ Benzene is widely recognized as a leukemogen, and the Occupational Safety and Health
Administration is currently attempting to limit exposure to it more strictly. The proposed new regulation is a limit of
an eight hr timeweighted average of 1 ppm in place of the current limit of 10 ppm. The fundamental rationale for the
change is a perception that the current standard is associated with an inordinate excess of leukemia. The
epidemiologic literature on benzene and leukemia supports the inference that benzene causes acute myelocytic
leukemia. However, the available data are too sparse, or /have/ other limitations, to substantiate the idea that this
causal association applies at low levels ie, 110 ppm of benzene. Nonetheless, under the assumption that causation
does apply at such low levels, a number of researchers have performed risk assessments using similar data but
different methodologies. The assessments that is considered acceptable suggest that, among 1,000 men exposed to
benzene at 10 ppm for a working lifetime of 30 years, there would occur about 50 excess deaths due to leukemia in
addition to the baseline expectation of seven deaths. However, this estimate is speculative and whether or not
enough confidence can be placed in it to justify a lower occupational benzene standard remain a decision for policy
makers. Abstract: PubMed
Austin H et al; Am J Epidemiol 127 (3): 41939 (1988)
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/EPIDEMIOLOGY STUDIES/ A retrospective cohort study was conducted in 233 benzene factories and 83 control
factories in 12 cities in China. The benzene cohort and the control cohort consisted of 28,460 benzene exposed
workers 178,556 personyears in 197281 and 28,257 control workers 199,201 personyears. Thirty cases of
leukemia 25 dead and 5 alive were detected in the former and four cases all dead in the latter. The leukemia
mortality rate was 14/100,000 personyears in the benzene cohort and 2/100,000 personyears in the control cohort;
the standardized mortality ratio was 5.74 p less than 0.01 by U test. The average latency of benzene leukemia was
11.4 years. Most 76.6% cases of benzene leukemia were of the acute type. The mortality due to benzene leukemia
was high in organic synthesis plants followed by painting and rubber synthesis industries. The concentration of
benzene to which patients with a leukemia were exposed ranged from 10 to 1000 mg/cu m mostly from 50 to 500
mg/cu m. Of the 25 cases of leukemia, seven had a history of chronic benzene poisoning before the leukemia
developed.[Jin C et al; Br J Ind Med 44 2: 1248 1987] Full text: PMC1007793 Abstract: PubMed
from HSDB
/EPIDEMIOLOGY STUDIES//The possible association of thinner, a mixture of seven organic solvents used in the
Mexican auto and paint industry, with the frequency of sister chromatid exchanges in the peripheral lymphocytes of
24 industrial workers was investigated. The subjects worked in a factory and three workshops in which no protective
measures against inhalation of vapors were taken. A matched comparison group consisted of 24 administrative and
outdoor workers. Use of cigarettes, alcohol, and medicines, and presence of viral infections within the 3 previous
months were determined by questionnaire. Blood was cultured for 72 hr with phytohemagglutinin, with 5
bromodeoxyuridine added at 24 hr and colchicine at 70 hr. Sister chromatid exchanges were scored from 50
metaphases from each individual. Air samples to determine concentrations of thinner components in the working
atmosphere were taken on the day of blood sampling and analyzed by gas chromatography. Solvent concentrations
in the samples from the factory air were methyl isobutyl ketone 2.4 ppm, methanol 0.6 ppm, isopropanol 3.3 ppm,
toluene 3.3 ppm, benzene 6.0 ppm, and hexane 3.3 ppm. The concentrations were below the limits recommended by
NIOSH ... except for benzene which was six times the NIOSH limit. One way analysis of variance of the sister chromatid
exchanges frequency for the exposed and comparison groups showed no differences for exposures of either 5 years
or less of 6 to 35 years. However, a significant increase of sister chromatid exchanges was found for tobacco use in
the exposed group but not for the comparison group. The implications of this result were discussed principally in
relation to benzene. ... Working conditions should be improved by a ventilation system and that a benzene free
thinner be substituted for the one being used. Abstract: PubMed
Souza V, Puig M; Mutat Res 189 (3): 35762 (1987)
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/EPIDEMIOLOGY STUDIES/ Dose response analyses for a cohort study of chemical workers exposed to benzene were
reported. Exposure information included 8 hour timeweighted averages and peak exposures and was used to
calculate the latency, duration of exposure, and peak exposure for several types of lymphatic and hematopoietic
cancers. The cohort included 4,602 male chemical workers from seven companies who were occupationally exposed
to benzene for at least 6 months between 1946 and 1975. A comparison group included 3,074 workers at the same
plants who were employed for at least 6 months without exposure to benzene. Workers exposed to benzene 5 and 14
years showed an increased risk of lung cancer with a statistically significant enhancement of the standardized
mortality ratio. Increased in reticulosarcoma and lymphosarcoma were related to the duration of continuous benzene
exposure. Increased latency was related to a slight enhancement for all cancers among the exposed workers. Analysis
by cumulative exposure demonstrated an increasing trend for death due to lymphatic and hematopoietic cancer,
lymphosarcoma, reticulosarcoma, and leukemia. Workers with a cumulative exposure of 180 to 719 ppm month
showed a significant increase in lung cancer. No dose response relation was detected for any other causes of death.
Wong O; Brit J Indust Med 44 (6): 38295 (1987)
from HSDB
/EPIDEMIOLOGY STUDIES/ A mortality study of 7,676 male chemical workers occupationally exposed to benzene was
described. The subjects were employed at nine plants belonging to seven member companies of the Chemical
Manufacturers Association. Workers were classified according to their benzene exposure into occupationally exposed
or comparison groups. Occupationally exposed workers received at least 6 months of continuous or intermittent job
exposure to benzene between 1946 and 1975. The comparison group comprised workers with at least 6 months of
employment at the same plant with no benzene exposure. Approximately 40% of the cohort were not occupationally
exposed to benzene, and about 46% of the cohort had received continuous exposure to benzene. The remaining 14%
fell into the intermittent exposure group. The observed mortality of the cohort was compared with the expected
based on the United States mortality rates appropriately standardized. Standardized mortality ratios were determined
for lymphatic and hematopoietic cancer, leukemia, non Hodgkin's lymphoma, and nonHodgkin's lymphopoietic
cancer. The number of observed deaths in the continuous exposure group was slightly but not significantly greater
than expected. Deaths from lymphatic and hematopoietic cancers and from leukemia were greater than expected in
the continuous exposure group. The mortality of the intermittent exposure group was comparable to the expected
mortality. The standardized mortality ratios of the total group were greater than the comparison group. Statistically
significant associations were demonstrated between benzene exposure and both lymphopoietic cancer and leukemia.
Wong O; Brit J Indust Med 44 (6): 36581 (1987)
from HSDB
/EPIDEMIOLOGY STUDIES/ Comprehensive comparative studies were conducted on the three groups of 148 male and
167 female workers exposed to benzene, toluene, or a combination of the two to evaluate subjective symptoms and
hematologic effects of the compounds. Exposed workers were compared to 127 unexposed referents. The exposure
intensity of the workers was estimated by diffusion dosimetry, and their subjective symptoms were obtained from
questionnaires. The workers in the benzene group were engaged in shoe making and printing; the toluene group was
engaged in shoe making and audio equipment production, and the mixed exposure group was employed in spray
painting in automobile body shops. The mean age of the workers ranged from 26.7 to 39.0 years. The average 7 hr
time weighted exposure to benzene was 33 and 59 ppm for men and women, respectively; the exposure
concentrations of toluene were 46 and 41 ppm for men and women, respectively. In the mixed exposure group, men
were exposed to 14 ppm of benzene and 18 ppm of toluene; the female mixed exposure was 18 ppm of benzene and
21 ppm of toluene. Hematological examinations showed no significant differences between exposed and nonexposed
workers, although leukocytes were marginally decreased. The prevalence of subjective symptoms was dose related
and statistically significant for both men and women. The number of symptoms per person during work was at least
ten fold higher in the exposed than in the nonexposed groups. The most frequent symptoms were dizziness, sore
throat, and headache which occurred during work as well as during non work time. This study provides no indication
of pancytopenia, and that both liver and kidney functions are unchanged under exposure conditions.
Yin S et al; Indust Health 25 (3): 11330 (1987)
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/EPIDEMIOLOGY STUDIES/ Personal air monitors and breath samples were used to measure benzene and other
volatile compounds in the breath of 200 smokers and 322 nonsmokers in New Jersey and California during 12 hr
sampling periods. The monitor measured only sidestream and exhaled mainstream smoke. Concentrations were also
measured in a subsample of homes and outdoor air. Compared to nonsmokers, benzene was significantly higher in
the breath of persons who had smoked tobacco the day they were monitored p< 0.001; values for smokers were 12
to 16 ug/cu m, nearly 10 times the breath level of nonsmokers. Values for personal air samplers were not always
significantly higher. Benzene in breath was related to number of cigarettes smoked. Based on direct measurements of
mainstream smoke, it was calculated that the typical smoker inhales 2 mg/day compared to the nonsmokers' intake of
<0.2 mg/day. Both smokers and nonsmokers exposed to passive smoking at home or work had increased levels of
benzene compared to nonsmoking situations p< 0.05. Indoor air levels in homes with smokers were significantly
greater than in nonsmoking homes in fall and winter but not during spring and summer. Abstract: PubMed
Wallace L et al; Arch Environ Health 42 (5): 2729 (1987)
from HSDB
/EPIDEMIOLOGY STUDIES/ Although the relationship between benzene and acute nonlymphocytic leukemia ANLL is
well established, most of the analytic cohort investigations examining the relationship between benzene and
hematologic neoplasms have evaluated only death certificates to validate diagnoses. In a followup study of 74,828
benzeneexposed and 35,805 nonexposed workers in China, pathology reports, medical records, and/or
histopathologic material were reviewed for all patients with hematopoietic malignancies to ensure correct
classification and to provide clinicopathologic descriptions. Eightytwo patients with hematopoietic neoplasms and
related disorders were identified among benzeneexposed workers, including 32 cases of acute leukemia, 7
myelodysplastic syndrome MDS, 9chronic granulocytic leukemia CGL, 20malignant lymphoma or related
disorder ML, 9aplastic anemia, and 5 others. Among the comparison group, 13 hematologic malignancies were
observed, including 6 patients with acute leukemia, 2CGL, 3ML, and 2 others. The hematopathologic characteristics
of the benzeneexposed ANLL cases resembled those following chemotherapy or radiotherapy. ANLL in workers
exposed to benzene may represent a distinct clinicopathologic entity, with characteristics similar to treatmentrelated
ANLL, including a preceding preleukemic phase in some patients. Results in our series, one of the largest to data, also
indicate that a greater diversity of hematologic neoplasms is evident among benzeneexposed workers than
previously described.
Travis LB et al; Leukemia and Lymphoma 14: 91102 (1994)
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/EPIDEMIOLOGY STUDIES/ Human metabolism of benzene involves pathways coded for by polymorphic genes. To
determine whether the genotype at these loci might influence susceptibility to the adverse effects of benzene
exposure, 208 Bulgarian petrochemical workers and controls, whose exposure to benzene was determined by active
personal sampling, were studied. The frequency of DNA singlestrand breaks DNASSB was determined by alkaline
elution, and genotype analysis was performed for five metabolic loci. Individuals carrying the NADPH:quinone
oxidoreductase 1 NQO1 variant had significantly twofold increased DNASSB levels compared to wildtype
individuals. The same result was observed for subjects with microsomal epoxide hydrolase EPHX genotypes that
predict the fast catalytic phenotype. Deletion of the glutathione Stransferase T1 GSTT1 gene also showed a
consistent quantitative 3540% rise in DNASSB levels. Neither glutathione Stransferase M1 GSTM1 nor
myeloperoxidase MPO genetic variants exerted any effect on DNASSB levels. Combinations of two genetic
polymorphisms showed the same effects on DNASSB as expected from the data on single genotypes. The three locus
genotype predicted to produce the highest level of toxicity, based on metabolic pathways, produced a significant 5.5
fold higher level of DNASSB than did the genotype predicted to yield the least genotoxicity. Abstract: PubMed
Garte S et al; J Toxicol Environ Health A. 71 (22): 14829 (2008)
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/SURVEILLANCE/ This paper is a followup on thirtyeight workers exposed from 1 to 24 years to average benzene
concentrations generally between 5 and 50 ppm, but as high as 90 peak of 140 in the case of one worker. One
individual was diagnosed as suffering from mild benzene poisoning and a small number of workers in the group had
blood changes considered abnormal, but blood dyscrasia or leukemia has not developed in 13 years after benzene
use was terminated in 1964. The population studied was small, but the data, nevertheless, would appear to support
the former ACGIH TLV of 25 ppm. One case of mild benzene poisoning reported from benzene exposures of the order
of 40 ppm suggests, however, that the margin of safety may be small. Abstract: PubMed
Pagnotto LD et al; Am Ind Hyg Assoc J 40: 137 (1979)
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/SURVEILLANCE/ A hematological investigation was carried out on 147 workers employed for +10 years exposed to
high benzene levels 320470 ppm. Abnormalities were noted in at least one parameter in 73%, the most common
one being thrombocytopenia, which occurred in 62% followed by anemia 35% and leucopenia 32%. Pancytopenia
occurred in 21% of the workers. During the 3 months following removal from exposure, hematological parameters
returned to normal in 120 workers, and one subject died. After one year, 20 of the remaining workers had only minor
abnormalities, six were still off work, and one was still hospitalized.
Savilahti M; Arch Gewerbpathol Gewerbhyg 15: 14757 (1956)
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/SURVEILLANCE/ A retrospective mortality study of a cohort of 594 men exposed to benzene at levels ranging
between 2 and 25 ppm TWA was carried out at the Dow Chemical Co between 19401973. No incr in total mortality
was noted with 102 observed/128 expected Standard Mortality Ratio SMR 80. A slight increase was noted in total
deaths due to malignancies 30 observed/22.8 expected, SMR 132 and suicide 5 observed/3.2 expected, SMR 147 as
well as deaths from leukemia 3 observed/0.8 expected and cancers of the digestive organs and peritoneum 9
observed/6.9 expected, SMR 125. If 53 workers exposed to other chemicals are excluded from malignancies, the
results would then be 24 observed/20.3 expected, SMR 108. Abstract: PubMed
Ott MG et al; Arch Environ Health 33: 310 (1978)
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/SURVEILLANCE/ ... Incidence of acute leukemia or 'preleukemia' among 28,500 shoeworkers in Turkey /was
estimated/ on basis of case ascertainment by contact with medical care. Thirty four cases were identified. ... Incidence
of acute leukemia was significantly greater among workers chronically exposed to benzene, which was used as a
solvent by these workers, than in the general population. Occupational exposures were determined by work histories
& by environmental measurements. There was said to be exposure only to benzene in small, poorly ventilated work
areas; peak exposures ... were reported to be 210650 ppM 6702075 mg/cu m. Duration ... was est to have been 1 to
15 yr mean 9.7 yr. Annual incidence was est to be 13/100000, giving approx relative risk of 2 when compared with
annual est for general population, 6/100000. These est are limited by study design characteristics & by uncertainty
about the way in which cases were ascertained, & how many of the study population were exposed & how many
unexposed.
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/SURVEILLANCE/ Occupational exposures were identified in rotogravure plants & shoe factories. Benzene concn near
rotogravure machines were 200400 ppM 6401280 mg/cu m, with peaks up to 1500 ppM 4800 mg/cu m; benzene
concn in air near workers handling glue in shoe factories were 25600 ppM 801920 mg/cu m, but were mostly
around 200500 ppM 6401600 mg/cu m. Est latency years from start of exposure to clinical diagnosis of leukemia
ranged from 324 yr median, 9 yr. ... The relative risk of acute leukemia was /est to be/ at least 20:1 for workers
heavily exposed to benzene in rotogravure & shoe industries in the provinces studied, when compared with general
population. The relative risk is based on a nonvalidated estimate.
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/SURVEILLANCE/ A historical cohort mortality study was conducted of 259 male employees of a chemical plant where
benzene has been used in large quantities. The study group included all persons who were employed by the
Company any time between January 1, 1947 and December 31, 1960. The cohort was followed through December 31,
1977 at which time 58 known deaths were identified. The only unusual finding was four deaths from lymphoreticular
cancers when 1.1 would have been expected on the basis of national mortality rates. Three of the deaths were due to
leukemia and one was caused by multiple myeloma. In addition, one of the leukemia deaths had multiple myeloma
listed on the death certificate. The findings are consistent with previous reports of leukemia following occupational
exposure to benzene and raise the possibility that multiple myeloma could be linked to benzene, also. Abstract:
PubMed
Decoufle P et al; Environ Res 30 (1): 1625 (1983)
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/SURVEILLANCE/ Hematologic & immunochemical investigations carried out in 270 workers with chronic exposure to
benzene demonstrated changes of the nucleologram & of the area of lymphocyte nucleoli & disorders of the humoral
immune response revealed by radial immunodiffusion. The numerical rise of bi & polynucleolated cells, of cells with
irregular macronucleoli & an enlargement of the nucleolar area reflected incr endolymphocytic amt of RNA. An incr
capacity of Ig formation, particularly of IgM, was also observed.
Chircu V et al; Rev Roum Med Interne 19 (4): 3738 (1981)
from HSDB
/SURVEILLANCE/ The possibility of there being a link between the apparent predominance of men with specific on the
job exposures to toxic materials among patients with hairy cell leukemia was explored. Of a total of 105 hairy cell
leukemia patients, eight were in the medical profession two Xray technicians, one radiologist, two pneumologists,
two orthopedists, and one internist, 21 were garage mechanics or divers of trucks or other heavy vehicles, eight
worked in construction as painters, decorators or masons, three were in the printing industry as photogravure and
equipment maintenance workers, ten were farmers, six were engineers and 49 held various technical or office
positions. Interviews were conducted with 69 of the patients. All those in medicine had used radioscopy for periods
exceeding 10 years. Exposure to petroleum derived substances was high not only among the garage mechanics and
drivers, but among those 49 individuals whose occupations did not have particular exposure, but whose hobbies and
paraprofessional activities involved use of benzene or other solvents. Of the 69 interviewed, 52 were able to
document exposure to benzene or other solvents.
Flandrin G, Collado S; Brit J Haematol 67 (1): 11920 (1987)
from HSDB
/SURVEILLANCE/ A study of mortality in automobile mechanics and gasoline service station workers in New
Hampshire was conducted. A proportionate mortality ratio analysis of all deaths occurring among male residents 20
years or older who lived in New Hampshire between 1975 and 1985 was performed. Occupation, industry, age, and
date and cause of death were obtained from death certificates. A total of 37,426 deaths were recorded. Of these, 453
were automobile mechanics and 134 were persons who had been employed in the gasoline service station industry.
Automobile mechanics had statistically significant proportionate mortality ratio elevations for suicide. Nonsignificant
increases in proportionate mortality ratio for leukemia, cancers of the oral cavity, lung, bladder, rectum and lymphatic
tissue, and nonmalignant blood dyscrasias and cirrhosis of the liver were observed. Workers in the gasoline service
station industry had statistically significant increases in mortality from leukemia and mental and psychoneurotic and
personality disorders, proportionate mortality ratio 328 and 394, respectively; however, the number of deaths was
small. Proportionate mortality ratio increases were also observed for emphysema and suicide. One or more of the
exposures experienced by automobile mechanics and service station workers presents a carcinogenic risk. The finding
of excess mortality from leukemia in both groups is consistent with exposure to benzene, a component of gasoline. ...
Workers who pump gasoline should be informed of the potential cancer hazard. Gasoline should not be used as a
solvent for removing grease and cleaning hands, and gasoline should not be siphoned by mouth.
Schwartz E; Amer J Indust Med 12 (1): 919 (1987)
from HSDB
/SURVEILLANCE/ Of a total of 528,729 workers exposed to benzene or benzene mixtures in China, 508,818 96.23%
were examined. Altogether 2,676 cases of benzene poisoning were found, a prevalence of 0.15%. A higher prevalence
of benzene poisoning was found in the cities of Hangjou, Hefei, Nanjing, Shenyang, and Xian. The geometric mean
concentration of benzene in 50,255 workplaces was 18.1 mg/cu m but 64.6% of the workplaces had less than 40
mg/cu m. There was a positive correlation between the prevalence of benzene poisoning and the concentration in
shoemaking factories. The prevalence of benzene induced aplastic anemia in shoemakers was about 5.8 times that
occurring in the general population. The results of this investigation show the need for a practicable hygiene standard
to prevent benzene poisoning.[Yin SN et al; Br J Ind Med 44 3: 1925 1987] Full text: PMC1007803 Abstract:
PubMed
from HSDB
/SURVEILLANCE/ Hematologic surveillance data from 1940 to 1975 were analyzed for a benzeneexposed cohort of
459 rubber workers. The present analyses are restricted to 161 workers with "preemployment" counts done before
exposure and rely on their subsequent counts from the first 12 months of employment. While blood cell counts
declined approximately 1000 cells/cu mm over the first 4 months of exposure. Using repeatedmeasures analysis of
variance, workers exposed above the median benzene exposure at the plant had significantly lower average white and
red blood cell counts at each month during the first year of work when compared with workers exposed below the
median. These decreased counts suggest that clinically detectable bone marrow depression accompanied the onset of
work in this plant during the 1940s and support exposure assessments that favor higher benzene levels in the 1940s
when compared with subsequent decades. The general utility of repeatedmeasures analytic techniques for medical
surveillance data is also demonstrated by this analysis. Abstract: PubMed
Cody RP et al; J Occup Med 35 (8): 77682 (1993)
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/BIOMONITORING/ A study conducted to measure the concentration of benzene in the air and solvents at 40 small
and large workplaces in Turkey where workers had contracted leukemia and lymphoma. In addition, hematological
examinations were performed on the 231 workers employed at the facilities. The facilities manufactured and repaired
shoes, tires, leather works, automobiles, and farm equipment. The age of the workers ranged from 14 to 57 years and
the mean duration of exposure was 8.8 years range 1 month to 40 years. Case reports were presented for five
workers with 2 to 15 years of exposure who had developed acute myeloblastic leukemia, acute lymphoblastic
leukemia, acute myelomonocytic leukemia, Hodgkin's disease and poorly differentiated lymphoma. Benzene
concentrations in the solutions and thinners used ranged from 3 to 7.5%. The concn of benzene in air samples from
the plants ranged from 0 to 110 ppm while 76.4% of solvents contained more than 1% of benzene. Hematological
examinations of the workers showed that 32% of them had abnormal values. There has been a decline in the use of
benzene in Turkey since an earlier study in 1972, but that the percentages of benzene in most of the materials are still
above permissible limits.
Askoy M et al; Brit J Indust Med 44 (11): 7857 (1987)
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/GENOTOXICITY/ In expt in vitro, benzene did not change the number of sisterchromatid exchanges or the number
of chromosomal aberrations in human lymphocytes. Abstract: PubMed
GernerSmidt P, Friedrich U; Mutat Res 58 (23): 3136 (1978)
from HSDB
/GENOTOXICITY/ The mutagenic activity upon human lymphocytes was studied after its addn to culture on the 28th
hr of cultivation G1S periods. Concn of 1, 10, 25, 50, 100, & 250 ug/mL were studied. Benzene is a weak mutagen. It
caused elongation of centromere portions of chromosomes & chromosomal aberrations were mainly of single &
paired fragment type. Mutagenic activity was about the same in the G0 & G1S periods.
Mnatsakanov ST, Pogosyan AS; Biol Zh Arm 26 (12): 3843 (1973)
from HSDB
/GENOTOXICITY/ A doserelated increase in the number of cells with chromosomal aberrations occurred in human
lymphocyte cultures treated with 4X105 M and 3.0X103 M benzene for 53 hr prior to metaphase analysis. Cells in
late G2 stage were the most susceptible to the effect of benzene.
Morimoto K; Japan J Ind Health 8: 235 (1976)
from HSDB
/GENOTOXICITY/ A significantly increased frequency of chromatid and isochromatid breaks in the cultured
lymphocytes of workers in chemical laboratories and in the printing industry has been reported.
USEPA; Ambient Water Quality Criteria for Benzene p.C46 (1980) EPA 440/580018
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/GENOTOXICITY/ A significant increase of peripheral blood lymphocyte chromosomal aberrations in workers exposed
to benzene was reported, but not in those exposed to toluene and xylene.
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/GENOTOXICITY/ A report on 52 workers exposed to benzene found chromosomal aberrations chromosome breaks,
dicentric chromosomes, translocations, and exchange figures in peripheral lymphocytes at 23 times the rates found
in controls. The 8 hr TWA exposure was 23 ppm, the average concn determined by 15 min sampling was 25 ppm, and
the peak concn was 50 ppm.
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/GENOTOXICITY/ Thirty two patients who had recovered from a blood disease bone marrow impairment caused by
benzene poisoning had significantly increased rates of "unstable" and "stable" chromosomes. Aberrations of
chromosomes were present for several years after cessation of the exposure and after recovery from poisoning.
Persistence of an increase of the "stable" changes was particularly remarkable.
Waldbott GL; Health Eff of Envir Poll p.214 (1973)
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/GENOTOXICITY/ Numerous studies have been carried out on the chromosomes of bonemarrow cells & peripheral
lymphocytes from people known to have been exposed to benzene. ... In many of these studies, significant incr in
chromosomal aberrations have been seen, which in some cases have persisted for years after cessation of exposure. ...
Bonemarrow cells & peripheral lymphocytes /have been exam/ from workers with current severe blood dyscrasias, &
... /followup studies have been done on/ several workers by repeated cytogenetic studies up to 12 yr after recovery
from benzeneinduced pancytopenia. Gross chromosomal abnormalities were characteristic of these cells; 70% of the
bonemarrow cells & lymphocytes in pt with acute poisoning showed karyotypic abnormalities. The authors could not
relate the frequency or type of chromosomal alterations to the severity of blood dyscrasia. Five yr after poisoning, all
... 5 patients studied still showed stable cs & unstable cu chromosomal aberrations in ... lymphocytes, although only
40% of cells were now abnormal. By 12 yr ... no cytogenetic abnormalities remained in the 4 patients studied.
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/GENOTOXICITY/ Metabolic activation of benzene by rat liver microsomes & a reduced nadpgenerating system S9
mix induced sister chromatid exchanges SCE & cell division delays in cultured human lymphocytes. There were
optimal concn of S9 mix for the conversion of benzene into the active metabolites that exerted these cytotoxic
effects. Abstract: PubMed
Morimoto K; Cancer Res 43 (3): 13304 (1983)
from HSDB
/GENOTOXICITY/ Currently the most applied technique for monitoring biological effects of exposure to genotoxic
chemicals in industrial workers is the measurement of chromosome aberrations in peripheral blood lymphocytes. In
the Shell petrochemical complex in the Netherlands cytogenetic monitoring studies have been carried out from 1976
till 1981 inclusive, in workers potentially exposed to a variety of genotoxic chemicals, ie vinyl chloride, ethylene oxide,
benzene, epichlorohydrin, epoxy resins. Average exposure levels to these chemicals were well below the occupational
exposure limits. Results of thesse studies indicate that no biologically significant increase in the frequencies of
chromosome aberrations in the exposed populations occurred compared with control populations. ... Experience with
this methodology has shown that the results of chromosome analyses are difficult to interpret, due to the variable and
high background levels of chromosome aberrations in control populations and in individuals. It is concluded that the
method is not sufficiently sensitive for routine monitoring of cytogenetic effect in workers exposed to the low levels of
genotoxic compounds. Abstract: PubMed
deJong G et al; Mutat Res 204 (3): 45164 (1988)
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/GENOTOXICITY/ Benzene and its five metabolites, muconic acid, hydroquinone, catechol, pbenzoquinone and
benzenetriol, have been shown to produce DNA damage in hman lymphocytes.
from HSDB
/ALTERNATIVE and IN VITRO TESTS/ The homozygous NQO1*2 polymorphism results in a null NQO1 phenotype and
is a susceptibility factor for occupational benzene poisoning. NQO1 plays an important role in detoxification of
benzenederived quinones but plays a role in numerous other nonmetabolic cellular functions. NQO1 is expressed in
endothelial cells of bone marrow which form the vascular stem cell niche important in stem cell homing and
mobilization. /The authors/ therefore employed a transformed human bone marrow endothelial cell HBMEC line to
define the effects of compromising NQO1 on endothelial function. Either inhibition or knockdown of NQO1 led to
decreased expression of the adhesion molecules Eselectin, VCAM1 and ICAM1 and decreased functional adhesion
of CD34+ progenitor cells after TNFalpha stimulation. Suicide inhibition or knockdown of NQO1 decreased
NFkappaB p105 precursor and NFkappaB p50 subunit levels as well as leading to decreased nuclear levels of
NFkappaB phosphop65. An additional function of endothelial cells is tube formation and angiogenesis which was
inhibited by the benzene metabolite hydroquinone suggesting that endothelial function may be affected at multiple
levels after exposure of NQO1*2 polymorphic individuals to benzene. These data demonstrate that NQO1 plays an
upstream role in NFkappaB signaling and adhesion molecule expression in HBMEC and that NQO1 has important
regulatory effects in its own right in addition to being a marker for Nrf2 activation. Metabolic susceptibility factors
such as NQO1 have roles in addition to detoxification of reactive intermediates and interrogation of these novel roles
can inform both mechanisms of toxicity and human risk assessment.[Ross D et al; Chem Biol Interact. 192 12: 1459
2011] Full text: PMC3155573 Abstract: PubMed
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/ALTERNATIVE and IN VITRO TESTS/ Cytochrome P450 2E1 CYP2E1 is an important metabolizing enzyme involved in
oxidative stress responses to benzene, a chemical associated with bone marrow toxicity and leukemia. /The authors/
aimed to identify the CYP2E1 genetic biomarkers of susceptibility to benzene toxicity in support of environmental and
occupational exposure prevention, and to test whether a model using immortal human lymphocytes might be an
efficient tool for detecting genetic biomarkers. Immortalized human lymphocyte cell lines with independent
genotypes on four CYP2E1 SNP sites were induced with 0.01% phenol, a metabolite of benzene. CYP2E1 gene
function was evaluated by mRNA expression and enzyme activity. DNA damage was measured by SingleCell Gel
Electrophoresis SCGE. Among the four SNPs, cells with rs2070673TT and rs2030920CC showed higher levels of
CYP2E1 transcription and enzymatic activity than the other genotypes in the same SNP site. Cells with higher gene
expression genotypes also showed higher comet rates compared with lower gene expression genotypes.These results
suggest that CYP2E1 rs2070673 and rs2030920 might be the genetic biomarkers of susceptibility to benzene toxicity
and that the immortalized human lymphocytes model might be an efficient tool for the detection of genetic
biomarkers of susceptibility to chemicals. Abstract: PubMed
Zhang J et al; Biomed Environ Sci. 24 (3): 3009 (2011)
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/IMMUNOTOXICITY/ ... A large number of workers exposed to but not seriously intoxicated by benzene /were studied
& results showed/ that serum complement levels, IgG, & IgA, were depressed but that IgM levels did not drop & were
in fact slightly higher Lange et al 1973; Smolik et al 1973. ... These /& other/ observations, taken together with well
known ability of benzene to depress leukocytes ... may explain why benzeneintoxicated individuals readily succumb
to infection & why terminal event in severe ... toxicity is often an acute, overwhelming infection.
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/IMMUNOTOXICITY/ /The authors/ have previously reported that benzene decreases peripheral white blood cell and
platelet counts and specifically lowers subsets of several blood cell types, including CD4+T cells, B cells, NK cells, and
granulocytes. Diminished thymus function has been implicated as a mechanism for CD4+T cell loss in other
conditions such as AIDS by assays of T cell receptor excision circles TRECs, a marker of naive T cells that have
recently emigrated from the thymus. To evaluate alteration of thymic function as a mechanism for benzene's effects
on CD4+T cell counts, /the authors/ measured total TREC levels in 45 benzeneexposed workers and 45 unexposed
controls. There was no significant difference in TREC levels per 106 peripheral blood leukocytes in the benzene
exposed workers compared to the controls. Although /the/ study does not rule out counterbalancing alterations of
TREC levels in specific T cell subsets, benzene's lymphotoxicity does not appear to be mediated through diminished
thymus function. Abstract: PubMed
Lan Q et al; Chem Biol Interact. 153154: 1115 (2005)
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/OTHER TOXICITY INFORMATION/ The hematotoxicity of benzene is expressed primarily as a bone marrow effect
leading eventually to complete destruction of myeloid and erythroid marrow components. This is manifested as a
marked decrease in circulating formed elements, ie red blood cells, and platelets. The resultant aplastic anemia is a
potentially fatal disorder which in its severe form has better than a fifty percent mortality rate. In both man and
laboratory animals the extent of bone marrow damage appears proportional to the dose of benzene. Lesser degrees
of bone marrow toxicity than aplastic anemia are more common in occupational exposure situations. Classically, the
discovery of one individual with significant bone marrow toxicity has led to evaluation of the exposed work force and
the finding of a wide variation in the extent of hematotoxicity. This has ranged from clinically significant pancytopenia,
in which are decreases in white blood cells leukopenia, red blood cells anemia, and platelets thrombocytopenia to
a situation in which only one of these is slightly below normal range. In the latter case it is of course difficult to
distinguish a benzene effect from that due to the extremes of normal variation or to mild intercurrent disease.
Mehlman MA, ed; Adv Mod Environ Toxicol Vol IV: Carcinogenicity and Toxicity of Benzene p.52 (1983)
from HSDB
/OTHER TOXICITY INFORMATION/ The type of leukemia most commonly associated with benzene is acute
myelogenous leukemia and its variants, including erythroleukemia and acute myelomonocytic leukemia. Acute
myelogenous leukemia is the adult form of acute leukemia and, until recent advances in chemotherapy, it was a
rapidly fatal disease. The other major acute form of leukemia, acute lymphocytic leukemia, has been reported to be
associated with benzene exposure but evidence of a causal association is weak. There is a somewhat stronger,
although still inconclusive, association in the literature between benzene exposure and the two common forms of
chronic leukemia: chronic myelogenous leukemia and chronic lymphocytic leukemia. Other hematological disorders
possibly associated with benzene exposure include Hodgkin's disease, lymphocytic lymphoma, myelofibrosis and
myeloid metaplasia, paroxysmal nocturnal hemoglobinuria, and multiple myeloma.
Mehlman MA, ed; Adv Mod Environ Toxicol Vol IV: Carcinogenicity and Toxicity of Benzene p.52 (1983)
from HSDB
/OTHER TOXICITY INFORMATION/ A variety of malignant disorders have been associated with solvent exposure, ie
acute leukemia, Hodgkin's disease odds ratio 2.86.6, nonHodgkin's lymphoma odds ratio 3.3 and myeloma, and
there are some indications that solvent exposure may be a risk factor for myelofibrosis. The carcinogenic effect of
benzene is epidemiologically and experimentally well documented and there are some indications that other solvents
may also be hazardous. Abstract: PubMed
Brandt L; Med Oncol Tumor Pharmacother 4 (3/4): 199205 (1987)
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/OTHER TOXICITY INFORMATION/ The leukemias currently account for approximately 3% of the total cancer
incidence and 4% of the cancer deaths in the USA. The average annual incidence is eight cases per 100,000 for
females and 11 cases per 100,000 for males. Leukemia is more common in whites than nonwhites and more common
in males. Acute nonlymphocytic accounts for about 30% of the total leukemia incidence and for over 85% of the acute
leukemia seen in persons over 40 years of age. Recent mortality data show very little change in leukemia death rates
except for acute nonlymphocytic leukemia which increased by 20% from 1969 to 1977. Genetic and environmental
factors were considered. Chromosome disorders and a family history may be etiological factors in both acute
nonlymphocytic leukemia and lymphocytic leukemia. Exposures to benzene, ionizing radiation, and antineoplastic
agents are known to cause chromosomal aberrations and leukemia; however, no evidence of a causal sequence of
events has been obtained. Environmental risk factors such as ionizing radiation, cigarette smoke, and chemicals were
described. Benzene is considered the best known and most widely occurring human leukemogen. A number of case
reports and cohort studies have linked benzene exposure and acute leukemias. Benzene associated relative risk for
overall leukemia generally range from 1.5 to 2.0. ...Some studies have shown that prior chemical exposures are
associated with chromosome aberrations in acute nonlymphocytic leukemic patients.
Sandler DP, Collman GW; Amer J Epidemiol 126 (6): 101732 (1987)
from HSDB
/OTHER TOXICITY INFORMATION/ /Evidence supports the conclusion that/ there exists reliable clinical and
epidemiological /studies/, concerning increased leukemogenic risk on working place with high benzene
concentrations in past years tens and even hundreds of ppm. Most epidemiological studies, indicate now that this
risk is also elevated in more favorable working conditions, although practical valuable doseeffect relationship
between benzene concentrations and rate of leukemogenic risks is still unknown. Results of experimental
investigations on problem of leukemogenic effects of benzene are contradictory. It was stated recently that there is a
lack of adequate experimental models of benzene blastomogenesis. Taking into consideration increasing economic
significance of benzene and existence of large contingents of workers dealing with benzene, it is necessary to
continue appropriate experimental and epidemiological investigations. Abstract: PubMed
Sokolov VV, Frasch VN; J Hyg Epidemiol Microbiol Immunol 31 (2): 13543 (1987)
from HSDB
/OTHER TOXICITY INFORMATION/ Animal expt show that benzene sensitizes the myocardium to epinephrine, so that
the endogenous hormone may precipitate sudden & fatal ventricular fibrillation.
III398
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13.1.22 NonHuman Toxicity Excerpts
/LABORATORY ANIMALS: Acute Exposure/ The effect of a single dose of benzene 0.5 mL/kg body wt ip on the heme
saturation of tryptophan pyrrolase activity in liver was examined /in female albino rats/. There was a significant
decrease in the heme saturation of hepatic tryptophan pyrrolase, suggesting depletion of regulatory heme. After
benzene administration there was significant increase in deltaaminolevulinate synthetase activity while delta
aminolevulinate dehydratase activity was significantly decreased, however, ferrochelatase and heme oxygenase
activities were unaltered. Administration of tryptophan to benzene pretreated rats showed a reversal of benzene
effects on heme synthesizing enzymes: there is an increase in the heme saturation of tryptophan pyrrolase and
decrease in deltaaminolevulinate synthetase. However, there was no significant alteration in the activity of delta
aminolevulinate dehydratase.
Siddiqui SM et al; Toxicol 48 (3): 24551 (1988)
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/LABORATORY ANIMALS: Acute Exposure/ Rats exposed to 3,5268,224 ppm of benzene in a closed chamber for 15
min exhibited an increased number of ectopic ventricular beats.
Magos GA et al; Neurotoxicol Teratol 12 (2): 11924 (1990)
from HSDB
/LABORATORY ANIMALS: Acute Exposure/ SpragueDawley rats received a single dose of 950 mg/kg benzene by
gavage and were sacrificed 2 hr after treatment. The control group received nothing. Brains were dissected ... Results
showed that benzene decreased acetylcholine content of rat hippocampus. 3,4Dihydroxyphenylalanine and
norepinephrine content decreased in the rat midbrain. Dopamine, serotonin and 5hydroxyindoleacetic acid content
increased in the rat midbrain. Dopamine, 3,4dihydroxyphenylacetic acid, norepinephrine, and 5hydroxyindoleacetic
acid content increased and serotonin content decreased in the rat hypothalamus after oral administration of benzene.
Increased dopamine, homovanillic acid, 3methoxy4hydroxyphenylglycol, and serotonin content of rat medulla
oblongata was observed. Decreased norepinephrine and 5hydroxyindoleacetic acid content of rat medulla oblongata
by benzene treatment was observed.
Kanada M et al; Ind Health 32: 14564 (1994)
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/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In series of chronic studies, bilateral cataracts were
found in 50% of rats exposed /to/ ... 50 ppm for 600 hr ...
National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 689
from HSDB
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Female Wistar rats were exposed to various solvent
vapors 8 hr/day for 7 days. The leukocyte suspension and serum were prepared from peripheral blood and utilized for
the determination of alkaline phosphatase activity with disodium phenyl phosphate as a substrate leukocyte alkaline
phosphatase and serum assay. While the exposure to benzene at 20 or 50 ppm did not cause significant changes in
leukocyte alkaline phosphatase assay activity, the exposure at 100 to 300 ppm resulted in a dosedependent increase
of leukocyte alkaline phosphatase assay activity up to more than 100% over the control. No further increase was
observed at 1000 or 3000 ppm. Similar exposure at 300 ppm to either toluene, mxylene, nhexane, trichloroethylene,
methyl ethyl ketone, ethyl acetate, or methyl alcohol did not induce any changes in leukocyte alkaline phosphatase
assay activity. Thus, the increase in leukocyte alkaline phosphatase assay activity was considered to be specific to
benzene exposure. When the animals were exposed to toluene 300 ppm in combination with benzene 300 ppm,
not only was the benzene induced leukopenia alleviated as previously reported, but the benzene induced increase in
leukocyte alkaline phosphatase assay activity was no longer observed. The parallel inhibitory effects of toluene on
benzene induced increase in leukocyte alkaline phosphatase assay and leukopenia suggest that a relation may exist
between increase in leukocyte alkaline phosphatase assay activity and leukopenia. No changes in serum alkaline
phosphatase assay activities were observed in the rats under the exposure conditions examined. Abstract: PubMed
Li GL et al; J Toxicol Environ Health 19 (4): 5819 (1986)
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/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Granulocytic hyperplasia has been detected in the bone
marrow of mice exposed to 300 ppm benzene in air for 6 hr/day, 5 days/wk for 16 wk, and held 18 mos after the last
exposure.
Farris GM et al; Fundam Appl Toxicol 20 (4): 5037 (1993)
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/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ /Researchers/ observed a 26% decrease in spleen
weight in male Kunming mice exposed to 12.52 ppm benzene 2 hr/day, 6 days/wk for 30 days. Examination of the
bone marrow showed decreases in myelocytes, premyelocytes, myeloblasts, and metamyeloblasts at the same dose
level.
Li L et al; Biomed Environ Sci 5 (4): 34954 (1992)
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/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Experimental DBA/2 mice were exposed to 300 ppm
benzene for 6 hr/day for 5 days/wk Regimen 1 or 3 day/wk Regimen 2 for a duration of 113 wk. Polychromatic
erythrocytes were affected by benzene inhalation independent of exposure duration and regimen, while
normochromatic erythrocytes were affected only following Regimen 1 exposure. Males were more sensitive to
benzene inhalation than females.
Luke CA et al; Mutat Res 203: 25171 (1988)
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/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... 30 Male AKR, DBA2, C3H or C57Bl6 mice were given
weekly sc injections of 0.001 mL benzene in 0.1 mL olive oil for life. No tumors were found in mice of DBA2, C3H or
C57Bl6 strains, the max lifespan being 730 days. Between 7th & 16th mo of treatment 16/30 treated AKR mice died
with leukemia, in addition, 8 died before age of 9 mo without leukemia. However, leukemia was also observed in
30/35 AKR untreated mice which lived, on avg, longer than test animals.
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/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Lifetime exposure of C57Bl/6J mice to 100 or 300 ppM
320 or 958 mg/cu m benzene produces anemia, lymphocytopenia & neutrophilia assoc with a relative incr in the
number of immature leucocytes & decr in mature leucocytes in circulation. Subcutaneously admin benzene led to a
selective depression in Blymphocytes in rabbits, whereas T lymphocytes were more resistant. Abstract: PubMed
Green JD et al; Toxicol Appl Pharmacol 46 (1): 918 (1978)
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/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Male Charles River CD1 mice number unspecified
were exposed for 6 hr/day, 5 days/wk, for life to atmospheres containing ... levels of 0 control, 100 ppm 320 mg/cu
m or 300 ppm 958 mg/cu m. Two mice in highexposure group develop myelogenous myeloid leukemia. ... There
was no evidence of leukemic response in 45 male 6 wk old SpragueDawley rats exposed to ... 900 mg/cu m 300
ppm ... for 6 hr/day, 5 days/wk, for life. Exposure was terminated at wk 99 when the last test animal died. Controls
were 27 males of same strain & age. ... SpragueDawley rats & AKR mice exposed to benzene 300 ppm, 958 mg/cu
m for 6 hr/day, 5 days/wk for life had lymphocytopenia, with little evidence of anemia. AKR mice were more sensitive
to benzeneinduced leucopenia than ... rats. /Mice also displayed agranulocytosis & reticulocytosis. No evidence of
leukemia was reported/.
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/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Weanling male C57BL/6N mice were subcutaneously
injected twice weekly for 44 weeks and once weekly for the last 10 weeks, gradually incr the dose from 450 mg/kg to
1.8 g/kg. The mice were killed 104 weeks after the first injection, and no evidence of carcinogenic activity was found in
either the benzenetreated mice or the negative controls. Butylnitrosourea induced leukemia, lymphomas, and/or
intestinal neoplasms/were observed/ in almost all the positive controls.
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/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Two groups of 40 male C57Bl/6J mice, 6 wk old, were
exposed to atmospheres containing 0 or 900 mg/cu m 300 ppm benzene for 6 hr/day, 5 days/wk, for life. The
exposure ended after 488 days with the death of the last test mouse. In addn to anemia, lymphocytopenia,
neutrophilia & bonemarrow hyperplasia, 6 of 40 mice exposed ... developed lymphocytic lymphoma with thymic
involvement p< 0.01 for lymphomas, according to peto's logrank method, 1 plasmacytoma & 1 hematocytoblastic
leukemia. Avg survival time of the 8 tumorbearing mice was 262 days. Two of the 40 control animals died from
lymphocytic lymphoma with no thymic involvement after 282 & 608 days, respectively. Differences in incidence &
induction time of tumors between the groups were statistically significant.
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/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Three groups of 30 or 35 male & ... female Sprague
Dawley rats, 13 wk old, received 50 or 250 mg/kg body wt benzene purity unspecified dissolved in pure olive oil by
stomach tube once daily on 4 or 5 days each wk during 52 weeks. Groups of 30 male & 30 female controls received
olive oil only. The rats were allowed to live until spontaneous death or were killed at 144 weeks, the end of expt; avg
survival times were unspecified. Of females of the control, low & highdose groups, 0/30, 2/30 & 8/32, respectively,
developed zymbal gland carcinomas CochranArmitage test for pos trend; p= 0.001; Fisher exact test for control
versus highdose group: p= 0.003; 3/30, 4/30 & 7/32 developed mammary gland carcinomas; & 1/30, 2/30 & 1/32
developed leukemias. No such tumors were found in males, except that leukemias occurred in 4/32 highdose males
CochranArmitage test for pos trend; p= 0.008; Fisher exact test: p< 0.069. Background incidence of zymbal gland
carcinomas in several thousand male & female rats of same strain ... /was/ about 0.7%. Avg latent period of mammary
gland carcinomas was 88 wk in each test groups versus 110 wk in control ... .
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/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Benzene hematotoxicity and leukemogenesis were
investigated to verify epidemiological estimates to the effect that leukemia had developed in human beings exposed
to benzene for about 15% of their lifetime, and that the levels of exposure reached at times as high as 250 to 300
ppm for at least a portion of working day. Based on a review of the literature and ongoing studies, mice were exposed
to benzene vapor for 6 hr/day, 5 days/week for 16 weeks. Exposure of male CBA/Ca mice to 300 ppm benzene proved
to be highly carcinogenic and leukemogenic compared to unexposed controls. Male and female CBA/Ca mice
exposed to 100 ppm benzene, according to the same schedule, showed 30% mortality as compared to 12% in
controls, while for neoplasms the respective figures were 10% and 1%. In this case, exposure to benzene reduced the
cellularity of the bone marrow and the number of stem cells, while DNA synthesis increased. /Data indicates/ that
benzene is carcinogenic in both animals and man and although it is unlikely that the slope for animals and man would
be the same, the investigation of the linearity of the response would be helpful. Abstract: PubMed
Cronkite BP; Blood Cells 12 (1): 12937 (1986)
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/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... Under the conditions of these 2 yr gavage studies,
there was clear evidence of carcinogenicity of benzene for male F344/N rats, for female F344/N rats, for male B6C3F1
mice and for female B6C3F1 mice. For male rats, benzene caused increased incidences of Zymbal gland carcinomas,
squamous cell papillomas and squamous cell carcinomas of the oral cavity, and squamous cell papillomas and
squamous cell carcinomas of the skin. For female rats, benzene caused increased incidences of Zymbal gland
carcinomas, squamous cell papillomas, and squamous cell carcinomas of the oral cavity. For male mice, benzene
caused increased incidences of Zymbal gland squamous cell carcinomas, lymphomas, alveolar/bronchiolar carcinomas
and alveolar/bronchiolar adenomas or carcinomas combined, Harderian gland adenomas, and squamous cell
carcinomas of the preputial gland. For female mice, benzene caused increased incidences of malignant lymphomas,
ovarian granulosa cell tumors, ovarian benigh mixed tumors, carcinomas and carcinosarcomas of the mammary gland,
alveolar/bronchiolar adenomas, alveolar/bronchiolar carcinomas, and Zymbal gland squamous cell carcinomas. ...
Toxicology & Carcinogenesis Studies of Benzene in F344/N Rats and B6C3F1 Mice (Gavage Studies). Technical Report Series No. 289
(1986) NIH Publication No. 862545 U.S. Department of Health and Human Services, National Toxicology Program, National
Institute of Environmental Health Sciences, Research Triangle Park, NC 27709
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/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Rats, guineapigs, & rabbits exposed to 8088
ppm 256281 mg/cu m for 7 hr/day for 3040 wk had incr testicular wt & degeneration of seminiferous tubules. ...
Alteration of estrous cycles has been reported in rats exposed to 1.6 or 9.4 ppm 5 or 30 mg/cu m for 4 mo ... but
there was no effect on their subsequent fertility or litter size. ... In C3HJAX mice whose ovaries were painted directly
... & which were later mated, a high incidence of sc hemorrhages & tail defects was observed in offspring, which
persisted through 4 generations.
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/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ SpragueDawley rats were exposed to 100, 300, &
2200 ppm of benzene vapor in air for 6 hr daily on days 615 of gestation. The mean body wt & crownrump length
were lower than control groups only at the highest exposure level. Skeletal exam showed an incr in the number of
fetuses with delayed ossification of sternebrae in the 300 & 2200ppm groups. The female offspring appeared to be
affected to a greater extent than male fetuses with respect to the incidence of delayed ossification of sternebrae.
Lifetime exposure of C57Bl/6J mice to 100 or 300 ppM 320 or 958 mg/cu m benzene produces anemia,
lymphocytopenia & neutrophilia assoc with a relative incr in the number of immature leucocytes & decr in mature
leucocytes in circulation. Subcutaneously admin benzene led to a selective depression in Blymphocytes in rabbits,
whereas T lymphocytes were more resistant. Abstract: PubMed
Green JD et al; Toxicol Appl Pharmacol 46 (1): 918 (1978)
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/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Single sc injection of 3 ml/kg body wt ... on 1 of
days 1115 of gestation to CFI mice caused cleft palate, agnathia & micrognathia in offspring ... . No controls were
used, & it is very likely that these effects were produced by stress of the injection. Several other studies in pregnant
mice exposed to benzene, 2 & 4 mL/kg body wt sc, 0.3 to 1.0 mL/kg body wt orally or 500 ppm 1597 mg/cu m by
inhalation for 7 hr/day all failed to show any teratogenic effect, although reduced fetal wt & occasional
embryolethality were observed. Similarly, several inhalation studies in rats have shown embryolethality & reduced
fetal wt but only occasional teratogenic effects: SpragueDawley rats exposed to 10, 50, or 500 ppm 32, 160 & 1600
mg/cu m for 7 hr/day had low incidence of brain & skeletal defects but no embryolethality at 50 or 500 ppm, & no
abnormality or embryolethality at lower levels ... . No teratogenic effect was seen in pregnant rats exposed to 10 or 40
ppm 32 or 128 mg/cu m for 6 hr/day ..., to 313 ppm 1000 mg/cu m for 24 hr/day or for 6 hr/day ... or to 400 mg/cu
m 125 ppm for 24 hr/day Tatrai et al 1980. No teratogenic effect has been reported in rabbits injected sc with 0.25
ml/kg of a 40% benzene soln daily during pregnancy ... or in rabbits exposed by inhalation to 500 ppm 1600 mg/cu
m for 7 hr/day on days 618 of pregnancy.
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/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Rats exposed continuously to 209.7 ppm for 10
days prior to breeding showed a complete absence of pregnancy. 1/10 rats exposed to 19.8 ppm had resorbed
embryos. Females showed an inverse relationship between dose 0.3209.7 ppm and number of offspring.
Gofmekler VA; Hyg Sanit 33: 327 (1968)
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/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Groups of 5 to 10 pregnant SwissWebster mice

were exposed to concentrations of 0, 5, 10, or 20 ppm benzene from days 6 through 15 of gestation and offspring of
exposed dams were examined for untoward effects. Litter sizes, fetal weights, numbers of dead, resorbed, or
malformed fetuses were within control limits. In the fetuses day 16 of gestation, the number of mature erythroid
precursor cells CFUE was decreased at 20 ppm benzene. In the neonates, the number of CFUE cells was increased
at 20 ppm benzene. Granulocytic colony forming cells GMCFUC were affected by the 2 higher exposure
concentrations. Adult mice treated in utero when reexposed to benzene showed a more severe decrease in splenic
GMCFUC than controls. Abstract: PubMed
Keller KA, Snyder CA; Toxicology 42: 17181 (1986)
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/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ A review was presented of data for ... chemicals for
which either ovarian toxicity or carcinogenicity, or both, have been documented in recent studies /conducted by/ the
National Toxicology Program. In most cases, ovarian atrophy was commonly found after 90 days of exposure, and
ovarian hyperplasia and neoplasia after longer periods. Benzene administered by gavage produced ovarian atrophy,
cysts, hyperplasia and neoplasia in mice.[Maronpot RR; Environ Health Perspect 73: 12530 1987] Full text:
PMC1474570 Abstract: PubMed
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/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ /Benzene/ has been shown to be fetotoxic
following inhalation exposure in mice 1600 ug/cu m, 7 hr/day, gestation days 615 and in rabbits.
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/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In /a/ study of cultured rat embryos, /researchers/
evaluated the embryotoxic effects of benzene and several of its metabolites. Benzene at 1.6 mM produced little
embryotoxicity, with or without hepatic activating enzymes, but phenol showed significant embryotoxicity in the
presence of hepatic activation at concentrations as low as 0.01 mM. Trans,transmuconaldehyde was embryotoxic at
0.01 mM and embryolethal at 0.05 mM; hydroquinone, catechol, and benzoquinone were all 100% embryolethal at 0.1
mM.
Chapman DE et al; Toxicol Appl Pharmacol 128 (1): 12937 (1994)
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/GENOTOXICITY/ ... Studies have demonstrated the induction of chromosomal aberrations in bonemarrow cells from
mice, rats, and rabbits treated with single or multiple daily doses of benzene ranging from about 0.2 to 2.0 mL/kg per
day & given either sc or ip. Most of the induced aberrations were breaks or deletions; but chromosometype
aberrations also occurred, particularly after prolonged exposure, when toxicity, manifested by a drop in peripheral
blood leucocyte count, appeared. ... A significant elevated level of aberrations are seen up to 8 days after a single ip
injection of 0.5 mL/kg body wt in rats, whereas aberrations were significantly incr in mice 24 hr but not 7 days after
receiving a similar dose, 0.5 mL/kg body wt.
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/GENOTOXICITY/ Bone marrow cells from mice orally dosed with 562050 mg/kg on two successive days showed
doserelated incr in incidences of chromosomal gaps and single breaks, multiple breaks at or above 139 mg/kg,
pulverization at or above 348 mg/kg, and cytotoxicity at 2050 mg/kg. Abstract: PubMed
Siou G et al; Mutat Res 90: 2738 (1981)
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/GENOTOXICITY/ Mice orally dosed with 0.221.65 g/kg showed a positive doserelated increase in polychromatic
erythrocytes in the micronucleus test. Abstract: PubMed
Schmidt W; Mutat Res 31: 915 (1975)
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/GENOTOXICITY/ Chromosomal abnormalities in bone marrow cells have been reported as a consequence of
experimental benzene exposure in a number of species including rats, rabbits, mice, and amphibians.
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/GENOTOXICITY/ Chromatid deletions in metaphase chromosomes of bone marrow cells have been found in rats
given single doses of subcutaneous benzene at 2 ml/kg and in rats given 1 g/kg/day for 12 days.
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/GENOTOXICITY/ After rats were dosed with 0.5 mL/kg intraperitoneally, no dominant lethality was found; however,
incr chromatid and chromosomal aberrations were reported.
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/GENOTOXICITY/ Enzymes that activate and detoxify benzene are likely genetic determinants of benzeneinduced
toxicity.NADPH: quinone oxidoreductase1 NQO1 detoxifies benzoquinones, proposed toxic metabolites of
benzene. NQO1 deficiency in humans is associated with an increased risk of leukemia, specifically acute myelogenous
leukemia, and benzene poisoning. /The authors/ examined the importance of NQO1 in benzeneinduced toxicity by
hypothesizing that NQO1deficient NQO1/ mice are more sensitive to benzene than mice with wildtype NQO1
NQO1+/+; 129/Sv background strain. Male and female NQO1/ and NQO1+/+ mice were exposed to inhaled
benzene 0, 10, 50, or 100 ppm for 2 weeks, 6 hr/day, 5 days/week. Micronucleated peripheral blood cells were
counted to assess genotoxicity. Peripheral blood counts and bone marrow histology were used to assess
hematotoxicity and myelotoxicity. p21 mRNA levels in bone marrow cells were used as determinants of DNA damage
response. Female NQO1/ mice were more sensitive 6fold to benzeneinduced genotoxicity than the female
NQO1+/+ mice. Female NQO1/ mice had a 9fold increase 100 versus 0 ppm in micronucleated reticulocytes
compared with a 3fold increase in the female NQO1+/+ mice. However, the induced genotoxic response in male
mice was similar between the two genotypes > or = 10fold increase at 100 ppm versus 0 ppm. Male and female
NQO1/ mice exhibited greater hematotoxicity than NQO1+/+ mice. p21 mRNA levels were induced significantly in
male mice >10fold from both strains and female NQO1/ mice > 8fold, which indicates an activated DNA
damage response. These results indicate that NQO1 deficiency results in substantially greater benzeneinduced
toxicity. However, the specific patterns of toxicity differed between the male and female mice. Abstract: PubMed
Bauer AK et al; Cancer Res. 63 (5): 92935 (2003)
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/GENOTOXICITY/ Benzene, a carcinogen that induces chromosomal breaks, is strongly associated with leukemias in
humans. Possible genetic determinants of benzene susceptibility include proteins involved in repair of benzene
induced DNA damage. The catalytic subunit of DNAdependent protein kinase DNAPKcs, encoded by Prkdc, is one
such protein. DNAPKcs is involved in the nonhomologous endjoining NHEJ pathway of DNA doublestrand break
DSB repair. Here /the authors/ compared the toxic effects of benzene on mice C57BL/6 and 129/Sv homozygous
for the wildtype Prkdc allele and mice 129/SvJ homozygous for a Prkdc functional polymorphism that leads to
diminished DNAPK activity and enhanced apoptosis in response to radiationinduced damage. Male and female mice
were exposed to 0, 10, 50, or 100 ppm benzene for 6 hr/d, 5 d/week for 2 weeks. Male mice were more susceptible to
benzene toxicity compared with females. Hematotoxicity was evident in all male mice but was not seen in female
mice. /The authors/ observed similar, large increases in both micronucleated erythrocyte populations in all male mice.
Female mice had smaller but significant increases in micronucleated cells. The p53dependent response was induced
in all strains and genders of mice following benzene exposure, as indicated by an increase in p21 mRNA levels in bone
marrow that frequently corresponded with cell cycle arrest in G2/M. Prkdc does not appear to be a significant genetic
susceptibility factor for acute benzene toxicity. Moreover, the role of NHEJ, mediated by DNAPK, in restoring
genomic integrity following benzeneinduced DSB remains equivocal. Abstract: PubMed
Faiola B et al; Toxicol Sci. 75 (2): 32132 (2003)
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/ALTERNATIVE and IN VITRO TESTS/ Benzene is a potent bone marrow toxin in animals and man. Animal studies have
shown that exposure to benzene can alter lymphocyte functions and decrease the resistance of animals to Listeria
monocytogenes and transplanted tumor cells. Mononuclear phagocytes participate in host resistance to Listeria and
tumor cells. The purpose of the studies presented here was to determine the effects of benzene and benzene
metabolites on macrophage functions and the ability of macrophages to be activated for functions which are
important in host defense. Benzene had no effects on macrophage function or activation for any of the functions
tested. Conversely, metabolites of benzene, catechol, hydroquinone, benzquinone, and 1,2,4benzenetriol had potent
and varied effects on macrophage function and activation. Benzoquinone inhibited the broadest range of functions
including release of hydrogen peroxide, Fc receptormediated phagocytosis, interferon gamma priming for tumor cell
cytolysis, and bacterial lipopolysaccharide triggering of cytolysis. Benzoquinone was also the most potent metabolite
causing inhibition at lower concentrations than the other metabolites. Hydroquinone inhibited hydrogen peroxide
release and priming for cytolysis and 1,2,4benzenetriol inhibited phagocytosis and priming for cytolysis. Catechol
only inhibited the release of hydrogen peroxide. None of the compounds tested inhibited the induction of class II
histocompatibililty antigens on the cell surface. All of the effects measured occurred using concentrations of
compounds which did not disrupt the cell integrity or inhibit general functions such as protein synthesis. Taken
together these data suggest that benzene metabolites alter macrophage function through several mechanisms
including inhibition of output enzymes and disruption of signal transduction systems. Abstract: PubMed
Lewis JG et al; Toxicol Appl Pharmacol 92 (2): 24654 (1988)
from HSDB
/ALTERNATIVE and IN VITRO TESTS/ The effects of five straight alkane petroleum hydrocarbons nC6 to nC10, as well
as benzene and toluene upon lysosomal enzymes of the lung were investigated. Pulmonary alveolar macrophages
were obtained from adult male Sprague Dawley rats and from 3 month old NewZealand white rabbits by bronchial
lavage. These cells were cultured and subsequently exposed to hydrocarbons in Leighton tubes. All hydrocarbons
examined were cytotoxic to cultured pulmonary alveolar macrophages in a dose dependent manner, with benzene
and toluene being least toxic. The concentration of hydrocarbon producing death in 50% of treated rat cells was 1.0
millimolar mM for nC8, 2.0 mM for nC7, 5 mM for nC9, and about 10 mM for nC6, nC10, benzene and toluene.
Concentrations of hydrocarbons that killed 50% of rabbit macrophages were about half those observed in the rat.
CathepsinD and, to a lesser extent, cathepsinB release were stimulated upon addition of hydrocarbons to the cell
media. A similar but more pronounced release of cathepsins was observed in isolated lysosomes as well. A significant
decrease in cell respiration rate and a time and dose dependent increase in lipid peroxidation were also observed
following exposure of macrophages to the tested hydrocarbons, particularly nC7 and nC8 alkanes. These results
support the concept of an association between chain length and cytotoxicity of hydrocarbons in pulmonary alveolar
macrophages. Abstract: PubMed
Suleiman SA; Arch Toxicol 59 (6): 4027 (1987)
from HSDB
/ALTERNATIVE and IN VITRO TESTS/ When mitochondria are incubated in vitro with 2200 mg/kg of benzene there is
an inhibition of RNA synthesis. Benzene also caused a dosedependent inhibition of RNA synthesis in vitro in
mitoplasts derived from cat and rabbit bone marrow mitochondria. Exogenous NADPH is required for inhibition of
mitochondrial RNA synthesis in all these systems which suggests that benzene must be bioactivated within the
organelle. Toluene does not inhibit RNA synthesis and the simultaneous addition of equimolar toluene and benzene
results in protection against benzene inhibition. Both liver and bone marrow mitochondria incubated 3H with
benzene appear to activate benzene to a metabolite which can covalently bind to guanine residues of DNA. Benzene
also inhibits mitochondrial translation. Abstract: PubMed
Kalf GF et al; ChemBiol Interact 42 (3): 35370 (1982)
from HSDB
/OTHER TOXICITY INFORMATION/ /An/ ... animal study ... investigated the effects of acute inhalation exposure to high
concentrations of benzene vapor on the heart muscle of cats and monkeys. Information from the electrocardiograms
indicated that exposure to benzene vapor caused extra systoles and ventricular tachycardia of the prefibrillation type.
Animals that had their adrenals and stellate ganglias removed did not exhibit extra systoles or ventricular tachycardia.
These findings suggest that the arrhythmias were caused by catecholamine release and sympathetic discharge.
from HSDB
/OTHER TOXICITY INFORMATION/ Rabbits and rats injected subcutaneously with 0.2 mg/kg/day showed an incr
frequency of bone marrow mitoses.
Dobrokhotov VB; Gig Sanit 37: 36 (1972)
from HSDB
/OTHER TOXICITY INFORMATION/ Benzene is a mitotic poison, producing a decr in DNA synthesis in animal bone
marrow cells in vitro.
from HSDB
/OTHER TOXICITY INFORMATION/ The best evidence that benzene must be metabolized to produce bone marrow
depression is based on: 1 the observation that benzene toxicity is prevented by coadministration of toluene, which
inhibits benzene metabolism; and 2 that partial hepatectomy which decreases benzene metabolism also decreases
benzene toxicity.
from HSDB
/OTHER TOXICITY INFORMATION/ Reports indicate that protection against benzene toxicity in phenobarbital treated
animals reflects the fact that phenobarbital increased the detoxification rate of benzene in the liver. Inhibition of
metabolism by toluene and by aminotriazole has been found to protect animals by decreasing the rate of formation
of toxic metabolites.
from HSDB
/OTHER TOXICITY INFORMATION/ Benzeneinduced hematopoietic toxicity is an aryl hydrocarbon receptor AhR
related adverse effect that is not exhibited in AhRknockout KO mice. In the hematopoietic system, the steadystate
expression of AhRs is limited in the hematopoietic progenitor cells; thus, a hierarchical hematopoietic impairment
starts from hematopoietic progenitor cells after benzene exposure. When one looks at wildtype recipient mice that
have been lethally irradiated and repopulated with AhRKO bone marrow cells, owing to reconstruction by the
marrow from AhRKO mice, no impairment is observed in the assay of granulomacrophage colonyforming units
CFUGMs in the bone marrow after benzene exposure of the reconstituted mice. In contrast, in mature white blood
cells concern, benzeneinduced hematopoietic cytotoxicity is observed in the same reconstituted mice; however, this
benzeneinduced hematopoietic cytotoxicity in mature white blood cells is not induced in the case of AhRKO mice
repopulated with wildtype bone marrow cells after a lethal dose of irradiation. The mechanism of benzeneinduced
hematopoietic toxicity in the mature blood cells in AhRKO mice is assumed to be based on metabolites such as
phenol and hydroquinone derived from hepatic AhR. Thus, the former toxicity in mature white blood cells is assumed
to be based on the metabolites of the wildtype hepatic AhR, whereas the latter lack of toxicity in mature blood cells
in AhRKO mice is due to the lack of benzeneinduced metabolism in the liver. Global gene expression analysis of
bone marrow cells after benzene exposure reveals that MEF2c, the functions of which are known to maintain
lymphocyte differentiation and promote proliferation of hematopoietic progenitor cells, is commonly downmodulated
not only in C57BL/6 but also in C3H/He mice. In response to these impairments of the hematopoietic progenitor cells
and the niches, stochastic and reciprocal upregulations of integrin beta 2 and the Runx family are observed, which are
known to stabilize hematopoietic niches during the steadystate. Direct observation of the hematopoietic progenitor
cells, particularly the Linckit+Sca1+ LKS fraction, after benzene exposure revealed an increased amount of
intracytoplasmic reactive oxygen species ROS detected by ROSreacting dye as compared with other blood cell
fractions. Abstract: PubMed
Hirabayashi Y, Inoue T; Chem Biol Interact. 184 (12): 2528 (2010)
from HSDB
/OTHER TOXICITY INFORMATION/ Quinone oxidoreductases NQO1 and NQO2 are cytosolic proteins that catalyze
metabolic reduction of quinones and its derivatives to protect cells against redox cycling and oxidative stress. In
humans, a high percentage of individuals with myeloid and other types of leukemia are homo and heterozygous for
a null mutant allele of NQO1. The NQO2 locus is also highly polymorphic in humans. Recently, /the authors/
generated NQO1/ and NQO2/ mice deficient in NQO1 and NQO2 protein and activity, respectively. These mice
showed no detectable developmental abnormalities and were indistinguishable from wild type mice. Interestingly, all
the mice lacking expression of NQO1 and NQO2 protein demonstrated myelogenous hyperplasia of the bone marrow
and increased granulocytes in the peripheral blood. Decreased apoptosis contributed to myelogenous hyperplasia.
The studies on shortterm exposure of NQO1/ mice to benzene demonstrated substantially greater benzene
induced toxicity, as compared to wild type mice. Abstract: PubMed
Iskander K, Jaiswal AK; Chem Biol Interact. 153154:14757 (2005)
from HSDB
/OTHER TOXICITY INFORMATION/ Reactive oxygen species ROS, generated following benzene exposure, are
considered to trigger the development of hematopoietic neoplasms, although little supporting evidence has been
found. In this study, /the authors/ examined whether the experimental elimination of ROS generated following
benzene exposure prevents the development of benzeneinduced hematopoietic disorders to clarify the mechanism
underlying the development of benzeneinduced hematopoietic disorders. C57BL/6 mice, overexpressing human
thioredoxin hTrxTg, were used to examine the possible nullification of ROS induction following benzene exposure.
The experimental group was exposed to 300 ppm benzene 6 hours/day, 5 days/week, for 26 weeks, and lifetime
observation followed by molecular and histopathological examinations were carried out.The present study using h
TrxTg mice showed a complete suppression of the development of thymic lymphoma induced by benzene inhalation
0% in hTrxTg vs 30% in wildtype Wt mice. This was associated with a 48% decrease in the incidence of
clastogenic micronucleated reticulocyte induction in the hTrxTg mice compared with the Wt control after 2 weeks of
inhalation. As underlying mechanisms, the attenuation of oxidative stress was accompanied by a complete abrogation
of hematolymphoid toxicity, as shown by the upregulation of the activity of superoxidedismutase, and a
consequently stable ROS level, as determined by cell sorting using 2', 7'dichlorodihydrofluorescein diacetate, along
with a significant attenuation of the overexpression of a cell cycledependent kinase inhibitor, p21. The attenuation of
benzeneinduced oxidative stress and that of the consequent lymphomagenesis were observed for the first time, and
these indicate a role of oxidative stress in benzeneinduced clastogenesis and lymphomagenesis. These attenuations
were not seen in nonthymic lymphomas, and no leukemias developed in C57BL/6 used in this study. During the
constitutive overexpression of hTrx, the expression of arylhydrocarbon receptor in hTrxTg mice was
downregulated, which may also contribute to the attenuation. Abstract: PubMed
Li GX et al; Exp Hematol. 34 (12):168797 (2006)
from HSDB
13.1.23 Human Toxicity Values
Estimated oral doses from 930 g have proved fatal.

from HSDB
...concentrations of 66,000 mg/cu m 20,000 ppm commercial benzene have been reported to be fatal in man within
510 minutes.
from HSDB
Immediately dangerous to life and health = 500 ppm

from HSDB
13.1.24 NonHuman Toxicity Values
LD50 Mice ip 0.34 mL/kg Abstract: PubMed

Kocsis JJ et al; Science 160 (3826): 4278 (1968)
from HSDB
LD50 Rat oral 3306 mg/kg

NJ. 2004., p. 360
from HSDB
LC50 Rat ihl 10,000 ppm/7 hr

NJ. 2004., p. 360
from HSDB
LD50 Rat ip 2890 ug/kg

NJ. 2004., p. 360
from HSDB
LD50 Mouse oral 4700 mg/kg

NJ. 2004., p. 360
from HSDB
LC50 Mouse ihl 9980 ppm /time of exposure not stated/

NJ. 2004., p. 360
from HSDB
LD50 Mouse sc 882200 mg/kg bw

IUCLID Data Set for Benzene (71432); Available from, as of March 21, 2014:
http://esis.jrc.ec.europa.eu/doc/IUCLID/data_sheets/71432.pdf
from HSDB
LD50 Mouse ip 340 mg/kg

NJ. 2004., p. 360
from HSDB
LD50 Rabbit dermal >8260 mg/kg bw

from HSDB
LD50 Guinea pig dermal >8260 mg/kg bw

from HSDB
13.1.25 Ecotoxicity Values
LC100; Species: Tetrahymena pyriformis /protozoa/; Concentration: 1000 mg/L for 24 hr /Conditions of bioassay not
specified/
2001, p. 262
from HSDB
LC50; Species: Palaemonetes pugio grass shrimp; Concentration: 27 ppm for 96 hr /Conditions of bioassay not
specified/
263
from HSDB
LC50; Species: Cancer magister crab larvae stage 1; Concentration: 108 ppm for 96 hr /Conditions of bioassay not
specified/
2001, p. 263
from HSDB
LC50; Species: Crangon franciscorum shrimp; Concentration: 20 ppm for 96 hr /Conditions of bioassay not specified/
2001, p. 263
from HSDB
LC50; Species: Morone saxatilis bass; Concentration: 5.8 to 11 mg/L for 96 hr /Conditions of bioassay not specified/
2001, p. 263
from HSDB
LC50; Species: Poecilia reticulata guppy; Concentration: 63 mg/L for 14 days /Conditions of bioassay not specified/
2001, p. 263
from HSDB
LC50; Species: Salmo trutta brown trout yearlings; Conditions: static bioassay; Concentration: 12 mg/L for 1 hr
2001, p. 264
from HSDB
LC50; Species: Ambystoma mexicanum Mexican axolotl 34 wk after hatching; Concentration: 370 mg/L for 48 hr
/Conditions of bioassay not specified/
2001, p. 264
from HSDB
LC50; Species: /Carassius auratus/ goldfish; Concentration: 46 mg/L for 24 hr /soft water/ /Conditions of bioassay not
specified in source examined/
2001, p. 263
from HSDB
LC50; Species: /Lepomis macrochirus/ bluegill sunfish; Concentration: 20 mg/L for 2448 hr /Conditions of bioassay
not specified/
2001, p. 263
from HSDB
LC100; Species: /Lepomis macrochirus/ bluegill sunfish; Concentration: 34 mg/L for 24 hr /Conditions of bioassay not
specified/
2001, p. 263
from HSDB
LC100; Species: /Lepomis macrochirus/ bluegill sunfish; Concentration: 60 mg/L for 2 hr /Conditions of bioassay not
specified/
2001, p. 263
from HSDB
LC50; Species: Brine shrimp; Concentration: 6621 mg/L for 2448 hr /Conditions of bioassay not specified/
2001, p. 263
from HSDB
LC50; Species: /Pimephales promelas/ fathead minnow; Concentration: 35 to 33 mg/L for 24 hr96 hr soft water
/soft water//
2001, p. 263
from HSDB
LC50; Species: /Pimephales promelas/ fathead minnow; Concentration: 24 to 32 mg/L for 2496 hr hard water /hard
water//
2001, p. 263
from HSDB
LC50; Species: /Lepomis macrochirus/ Bluegill; Concentration: 22 mg/L for 2496 hr soft water /soft water/
2001, p. 263
from HSDB
LC50; Species: /Carassius auratus/ goldfish 34 mg/L for 2496 hr soft water
2001, p. 263
from HSDB
LC50; Species: /Gambusia affinis/ mosquito fish; Concentration: 395 mg/L for 2496 hr /Conditions of bioassay not
specified/
2001, p. 263
from HSDB
LC50; Species: Eisenia fetida Earthworm adult, weight 300500 mg; dermal 98 ug/sq cm for 48 hr 95% confidence
interval: 78123 ug/sq cm
Neuhauser EF et al; J Environ Qual 14 (3): 383388 (1985) as cited in the ECOTOX database. Available from, as of February 21,
2014: http://cfpub.epa.gov/ecotox/quick_query.htm
from HSDB
EC50; Species: Chlorella vulgaris Green Algae; Conditions: freshwater, static, 20 deg C; Concentration: 525000 ug/L
for 24 hr; Effect: growth, general /formulation/
Kauss PB, Hutchinson TC; Environ Pollut 9 (3): 157174 (1975) as cited in the ECOTOX database. Available from, as of February 21,
from HSDB
EC50; Species: Pseudokirchneriella subcapitata Green Algae; Conditions: freshwater, static; Concentration: 29000
ug/L for 72 hr; Effect: growth, general
Galassi S et al; Ecotoxicol Environ Saf 16 (2): 158169 (1988) as cited in the ECOTOX database. Available from, as of February 21,
from HSDB
EC50; Species: Pseudokirchneriella subcapitata Green Algae exponential growth phase; Conditions: freshwater, static;
Concentration: 41000 ug/L for 8 days; Effect: growth, general /formulation/
Herman DC et al; Aquat Toxicol 18 (2): 87100 (1990) as cited in the ECOTOX database. Available from, as of February 21, 2014:
http://cfpub.epa.gov/ecotox/quick_query.htm
from HSDB
EC50; Species: Ceriodaphnia dubia Water Flea; Conditions: freshwater, static, pH 7.7, hardness 65.2 mg/L CaCO3;
Concentration: 130 umol/L for 48 hr 95% confidence interval: 97179 umol/L; Effect: intoxication, immobilization
/>97% purity/
Rose RM et al; Arch Environ Contam Toxicol 34 (3): 248252 (1998) as cited in the ECOTOX database. Available from, as of February
21, 2014: http://cfpub.epa.gov/ecotox/quick_query.htm
from HSDB
LC50; Species: Ceriodaphnia dubia Water Flea age <24 hr; Conditions: freshwater, static, 25 deg C, pH 7.6, hardness
45.5 mg/L CaCO3, alkalinity 41 mg/L CaCO3, dissolved oxygen 7.3 mg/L; Concentration: 18400 ug/L for 24 hr 95%
confidence interval: 1540021900 ug/L /99.5% purity/
Marchini S et al; Environ Toxicol Chem 11 (2): 187195 (1992) as cited in the ECOTOX database. Available from, as of February 21,
from HSDB
LC50; Species: Xenopus laevis African Clawed Frog age 34 wk; Conditions: freshwater, static, 20 deg C;
Concentration: 190000 ug/L for 48 hr /formulation/
De Zwart D, Slooff W; Bull Environ Contam Toxicol 38: 345351 (1987) as cited in the ECOTOX database. Available from, as of
February 21, 2014: http://cfpub.epa.gov/ecotox/quick_query.htm
from HSDB
EC50; Species: Daphnia magna Water Flea age <24 hr; Conditions: freshwater, static, 20 deg C, pH 8.2, hardness 130
mg/L CaCO3; Concentration: 18000 ug/L for 24 hr 95% confidence interval: 1481021900 ug/L; Effect: intoxication,
immobilization />99.7% purity/
Tosato ML et al; Environ Sci Technol 25: 695702 (1991) as cited in the ECOTOX database. Available from, as of February 21, 2014:
from HSDB
EC50; Species: Daphnia magna Water Flea juvenile; Conditions: freshwater, static, 20 deg C; Concentration: 10000
ug/L for 24 hr; Effect: intoxication, immobilization /formulation/
Janssen CR, Persoone G; Environ Toxicol Chem 12: 711717 (1993) as cited in the ECOTOX database. Available from, as of February
from HSDB
EC50; Species: Daphnia magna Water Flea juvenile; Conditions: freshwater, static, 20 deg C; Concentration: 10000
ug/L for 48 hr; Effect: intoxication, immobilization /formulation/
Janssen CR, Persoone G; Environ Toxicol Chem 12: 711717 (1993) as cited in the ECOTOX database. Available from, as of February
from HSDB
EC50; Species: Daphnia magna Water Flea age 46 days, length 1.5 mm; Conditions: freshwater, static, 23 deg C, pH
67, dissolved oxygen 59 mg/L; Concentration: 400 mmol/cu m for 48 hr 95% confidence interval: 285554 mmol/cu
m; Effect: intoxication, immobilization /> or =97% purity/
Bobra AM et al; Chemosphere 12 (910): 11211129 (1983) as cited in the ECOTOX database. Available from, as of February 21,
from HSDB
LC50; Species: Daphnia magna Water Flea age < or =24 hr; Conditions: freshwater, static, 2022 deg C, pH 7.67.7;
Concentration: 1130000 ug/L for 24 hr /formulation/
Bringmann G, Kuhn R; Z WasserAbwasserForsch 10 (5): 161166 (1977) as cited in the ECOTOX database. Available from, as of
from HSDB
LC50; Species: Daphnia magna Water Flea age < or =24 hr; Conditions: freshwater, static, 22 deg C, pH 7.49.4,
dissolved oxygen 6.59.1 mg/L; Concentration: 250000 ug/L for 24 hr 200000310000 ug/L/> or = 80% purity/
LeBlanc GA; Bull Environ Contam Toxicol 24 (5): 684691 (1980) as cited in the ECOTOX database. Available from, as of February
from HSDB
LC50; Species: Daphnia magna Water Flea age < or =24 hr; Conditions: freshwater, static, 22 deg C, pH 7.49.4,
dissolved oxygen 6.59.1 mg/L; Concentration: 200000 ug/L for 48 hr 140000320000 ug/L /> or = 80% purity/
LeBlanc GA; Bull Environ Contam Toxicol 24 (5): 684691 (1980) as cited in the ECOTOX database. Available from, as of February
from HSDB
LC50; Species: Daphnia magna Water Flea mixed ages; Conditions: freshwater, static, 19 deg C; Concentration:
682000 ug/L for 48 hr 95% confidence interval: 608000752000 ug/L /formulation/
Eastmond DA et al; Arch Environ Contam Toxicol 13 (1): 105111 (1984) as cited in the ECOTOX database. Available from, as of
from HSDB
LC50; Species: Ictalurus punctatus Channel Catfish weight 0.1 g; Conditions: freshwater, static, 22 deg C, pH 7.4,
hardness 44 mg/L CaCO3; Concentration: 425000 ug/L for 24 hr 95% confidence interval: 357000505000 ug/L
/100% purity liquid/
Mayer FL,Jr, Ellersieck MR; USDOI/FWS, Resour Publ No.160: 505 (1986) as cited in the ECOTOX database. Available from, as of
from HSDB
from HSDB
LC50; Species: Ictalurus punctatus Channel Catfish weight 0.5 g; Conditions: freshwater, static, 17 deg C, pH 8,
from HSDB
from HSDB
from HSDB
from HSDB
from HSDB
from HSDB
from HSDB
LC50; Species: Lepomis macrochirus Bluegill weight 0.2 g; Conditions: freshwater, static, 19 deg C, pH 7.4, hardness
44 mg/L CaCO3; Concentration: 740000 ug/L for 24 hr 95% confidence interval: 584000937000 ug/L /100% purity
liquid/
from HSDB
liquid/
from HSDB
liquid/
from HSDB
liquid/
from HSDB
liquid/
from HSDB
liquid/
from HSDB
liquid/
from HSDB
LC50; Species: Lepomis macrochirus Bluegill weight 0.5 g; Conditions: freshwater, static, 17 deg C, pH 8, hardness
liquid/
from HSDB
LC50; Species: Lepomis macrochirus Bluegill weight 0.5 g; Conditions: freshwater, static, 17 deg C, pH 8, hardness
liquid/
from HSDB
LC50; Species: Lepomis macrochirus Bluegill weight 0.5 g; Conditions: freshwater, static, 17 deg C, pH 8, hardness 44
mg/L CaCO3; Concentration: 260000 ug/L for 96 hr 95% confidence interval: 213000311000 ug/L /100% purity
liquid/
from HSDB
LC50; Species: Lepomis macrochirus Bluegill weight 0.5 g; Conditions: freshwater, static, 17 deg C, pH 8, hardness 12
mg/L CaCO3; Concentration: 370000 ug/L for 96 hr 95% confidence interval: 285000481000 ug/L /100% purity
liquid/
from HSDB
LC50; Species: Oryzias latipes Japanese Medaka; Conditions: freshwater, static, 30 deg C; Concentration: 54000 ug/L
for 24 hr /formulation/
Tsuji S et al: Eisei Kagaku 32 (1): 4653 (1986) as cited in the ECOTOX database. Available from, as of February 23, 2014:
from HSDB
from HSDB
from HSDB
from HSDB
from HSDB
from HSDB
LC50; Species: Pimephales promelas Fathead Minnow age <24 hr larva; Conditions: freshwater, flow through, 25 deg
C, pH 7.65, hardness 45.5 mg/L CaCO3, alkalinity 39 mg/L CaCO3, dissolved oxygen 7.3 mg/L; Concentration: 15590
ug/L for 96 hr 95% confidence interval 1404017300 ug/L />99.5% purity/
from HSDB
LC50; Species: Pimephales promelas Fathead Minnow age 2833 days juvenile; Conditions: freshwater, flow through,
25 deg C, pH 7.65, hardness 45.5 mg/L CaCO3, alkalinity 39 mg/L CaCO3, dissolved oxygen 7.3 mg/L; Concentration:
24600 ug/L for 96 hr 95% confidence interval 2140028100 ug/L />99.5% purity/
from HSDB
LC50; Species: Pimephales promelas Fathead Minnow age <24 hr larva; Conditions: freshwater, flow through, 25 deg
C, pH 7.65, hardness 45.5 mg/L CaCO3, alkalinity 39 mg/L CaCO3, dissolved oxygen 7.3 mg/L; Concentration: 14010
ug/L for 7 days 95% confidence interval 1237015860 ug/L />99.5% purity/
from HSDB
LC50; Species: Pimephales promelas Fathead Minnow length 3.86.4 cm, weight 12 g; Conditions: freshwater, static,
25 deg C, pH 8.2, hardness 360 mg/L CaCO3, alkalinity 300 mg/L CaCO3, dissolved oxygen 7.8 mg/L; Concentration:
34420 ug/L for 24 hr 95% confidence interval 2410042830 ug/L /formulation/
Pickering QH, Henderson C; J Water Pollut Control Fed 38 (9): 14191429 (1966) as cited in the ECOTOX database. Available from,
as of February 24, 2014: http://cfpub.epa.gov/ecotox/quick_query.htm
from HSDB
from HSDB
from HSDB
from HSDB
from HSDB
from HSDB
LC50; Species: Oncorhynchus mykiss Rainbow Trout juvenile, weight 13.9 g, length 106 mm; Conditions: freshwater,
flow through, 15 deg C, pH 7.98.0, hardness 535596 mg/L CaCO3, alkalinity 147165 mg/L CaCO3, dissolved oxygen
7.0 mg/L; Concentration: 5300 ug/L for 96 hr
DeGraeve GM et al; Arch Environ Contam Toxicol 11 (4): 487490 (1982) as cited in the ECOTOX database. Available from, as of
from HSDB
LC50; Species: Oncorhynchus mykiss Rainbow Trout length 4.66.4 cm; Conditions: freshwater, flow through, 14.1
16.5 deg C, pH 7.608.19, dissolved oxygen 5.69.4 mg/L; Concentration: 277 umol/L for 96 hr
Hodson PV et al; Environ Toxicol Chem 3 (2): 243254 (1984) as cited in the ECOTOX database. Available from, as of February 24,
from HSDB
LD50; Species: Oncorhynchus mykiss Rainbow Trout length 7.69.6 cm; gavage 32.3 mmol/kg
from HSDB
LD50; Species: Oncorhynchus mykiss Rainbow Trout length 7.09.9 cm; ip 25.8 mmol/kg
from HSDB
LC50; Species: Oncorhynchus mykiss Rainbow Trout; Conditions: freshawater, renewal, 12 deg C, dissolved oxygen >
or =80%; Concentration: 5900 ug/L for 96 hr
Galassi S et al; Ecotoxicol Environ Saf 16 (2): 158169 (1988) as cited in the ECOTOX database. Available from, as of February 24,
from HSDB
LC50; Species: Oncorhynchus mykiss Rainbow Trout weight 2.4 g; Conditions: freshawater, static, 12 deg C, pH 7.4,
hardness 44 mg/L CaCO3; Concentration: 9200 ug/L for 24, 96 hr 95% confidence interval: 720011700 ug/L /100%
purity liquid/
from HSDB
13.1.26 National Toxicology Program Reports
During the 17week studies, groups of 10 or 15 male and female F344/N rats and B6C3F1 mice were gavaged 5 days
per week with benzene in corn oil 5 mL/kg at doses of 0 to 600 mg/kg. No benzene related deaths occurred; in rats
that received benzene, final mean body weights were 14%22% lower compared with vehicle controls and in mice,
slight doserelated reductions were observed less than 10% differences.
Institute of Environmental Health Sciences, Research Triangle Park, NC 27709; Available from, as of February 25, 2014:
http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr289.pdf
from HSDB
Two yr toxicology and carcinogenesis studies of benzene greater than 99.7% pure were conducted in groups of 50
F344/N rats and 50 B6C3F1 mice of each sex and for each dose. Doses of 0, 50, 100, or 200 mg/kg body weight
benzene in corn oil 5 ml/kg were administered by gavage to male rats, 5 days/wk for 103 wk. Doses of 0, 25, 50, or
100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 wk.
... Under the conditions of these 2 yr gavage studies, there was clear evidence of carcinogenicity of benzene for male
F344/N rats, for female F344/N rats, for male B6C3F1 mice and for female B6C3F1 mice. For male rats, benzene caused
increased incidences of Zymbal gland carcinomas, squamous cell papillomas and squamous cell carcinomas of the
oral cavity, and squamous cell papillomas and squamous cell carcinomas of the skin. For female rats, benzene caused
increased incidences of Zymbal gland carcinomas, squamous cell papillomas, and squamous cell carcinomas of the
oral cavity. For male mice, benzene caused increased incidences of Zymbal gland squamous cell carcinomas,
lymphomas, alveolar/bronchiolar carcinomas and alveolar/bronchiolar adenomas or carcinomas combined,
Harderian gland adenomas, and squamous cell carcinomas of the preputial gland. For female mice, benzene caused
increased incidences of malignant lymphomas, ovarian granulosa cell tumors, ovarian benigh mixed tumors,
carcinomas and carcinosarcomas of the mammary gland, alveolar/bronchiolar adenomas, alveolar/bronchiolar
carcinomas, and Zymbal gland squamous cell carcinomas. ...
Institute of Environmental Health Sciences, Research Triangle Park, NC 27709; Available from, as of February 25, 2014:
http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr289.pdf
from HSDB
13.1.27 TSCA Test Submissions
An evaluation of fertility was made in female Charles River CD rats 26/group exposed by inhalation to benzene at 0,
1, 10, 30 and 300 ppm for 6 hrs/day, 5 days/week during a 10 week premating treatment period and ensuing mating
period, and continued exposure for mated females daily for 6 hrs/day during gestation to day 20. Daily exposure was
resumed on day 5 of lactation until weaning day 21 of lactation. There were significant differences between treated
and control animals in the following: decrease in pup survival index for lactation day 421 at 10 ppm, no dose
response, decreased mean pup weights days 14 and 21 of lactation for highdose level, and decreased mean
absolute liver weights highdose female pups. There were no significant differences between treated and control
animals in the following: maternal mortality, body weights, inlife observations, pregnancy rates, mean number dead
pups, mean liver weights male pups at all levels, mean relative liver weights female pups at all levels, mean relative
and absolute kidney weights all female pups, or gross postmortem examinations of adult females or pups.
Bio Dynamics Inc.; An Inhalation Female Fertility Study With Benzene in Rats, Final Report. (1980), EPA Document No. FYIAX
04810110, Fiche No. 01100
from HSDB
Teratogenic effects were evaluated in pregnant female Sprague Dawley rats 40/group exposed via inhalation to
benzene at 0 two groups, 1, 10, 40 and 100 ppm for 6 hrs/day from days 615 of gestation. On day 20 of gestation,
the dams were sacrificed and the fetuses removed by cesarean section. There were significant differences between
treated and control groups only in the decreased mean fetal body weights of fetuses from dams exposed at the high
dose level. There were no significant differences between treated and control dams in the following: mortality, clinical
observations, body weight data, maternal gross pathology, pregnancy rates, mean number of corpora and
implantations, or implantation efficiencies. There were no significant differences between fetuses from treated and
control dams in the following: mean incidence of fetal resorptions, mortality, mean percentage of male fetuses/litter,
mean fetal body lengths, or fetal development.
Hazelton Laboratories America, Inc.; Inhalation Teratology Study in Rats, Benzene, Final Report. (1982), EPA Document No. FYIAX
04820127, Fiche No. 01270
from HSDB
The mutagenicity of benzene was evaluated in dominant lethal assay using four groups of 20 male SpragueDawley
rats receiving whole body exposures to nominal concentrations of test material at 1, 10, 30 and 300ppm in a dynamic
air flow chamber for 6hours/day, 5days/week for ten consecutive weeks. Following exposure, each male was mated
with two untreated females per week for two consecutive weeks. There was no effect of treatment for all dosed male
rats as indicated by: mortality, body weight data and inlife physical observations. Pregnancy rates and implantation
efficiency ratios of females mated to treated males was not significant different from control group females. Slight
increases in the mean number of dead implantations and mean mutagenic ratios i.e. no. dead implants/total
implants were noted for each week of the post treatment mating period for females mated to high dose males, but
these differences were not statistically significant compared to controls. Males were sacrificed after a 10week post
mating period and microscopic examination of testis/epididymides revealed twohigh dose males with testicular
lesions.
Bio/dynamics Inc.; A DominantLethal Inhalation Study with Benzene in Rats, Final Report, (1980), EPA Document No. FYIAX0481
0110, Fiche No. OTS00001100
from HSDB
As part of subchronic inhalation study, the ability of benzene to cause chromosome aberrations was evaluated in
bone marrow cells of 50/sex CD1 mice receiving whole body exposures to nominal concentrations of 0, 1, 10, 30
and 300ppm in dynamic air flow chamber for 6hours/day, 5days/week for 13 weeks. Following the last day of
exposure, animals received a single intraperitoneal injection of colchicine and were sacrificed. Bone marrow slides of
mice at the highest concentration 300ppm exhibited statistically significant increases chromosome aberrations
relative to the control.
Hazleton Laboratories America Inc.; Subchronic Inhalation Study in Mice and Rats, Final Report, (1983), EPA Document No. FYIAX
07830203, Fiche No. OTS00002031
from HSDB
As part of subchronic inhalation study, the ability of benzene to cause chromosome aberrations was evaluated in
bone marrow cells of 50/sex Sprague Dawley rats receiving whole body exposures to nominal concentrations of 0, 1,
10, 30 and 300ppm in dynamic air flow chamber for 6hours/day, 5days/week for 13 weeks. Following the last day of
exposure, animals received a single intraperitoneal injection of colchicine and were sacrificed. Bone marrow slides of
female rats at all exposure levels exhibited statistically significant increases in chromosome aberrations relative to the
control. Noexposure related cytogenic effects were apparent in any of the male rats.
Hazleton Laboratories America Inc.; Subchronic Inhalation Study in Mice and Rats, Final Report, (1983), EPA Document No. FYIAX
07830203, Fiche No. OTS00002031
from HSDB
The ability of benzene to increase the incidence of micronucleated polychromatic erythrocytes was evaluated in male
and female CD1 mice receiving nominal concentrations of 1, 10, 30 and 300ppm for 6hours/day, 5days/week for 13
weeks Micronucleus Test. Groups of 20 mice 10/sex/sample time were sacrificed after 0, 15, 30, 60 and 90 days of
exposure. Exposure to 300ppm benzene caused a significant increases in micronucleated polychromatic erythrocytes
PCEs and monochromatic erythrocytes NCEs in male and female mice at all sample times. Male mice exhibited a
greater response than female mice. The frequency of micronucleated PCEs and the frequency micronucleated NCEs
achieved steady state by the 30 day sample time. The rate of erythropoiesis, as measured by per cent of
polychromatic erythrocytes in the peripheral blood, was not significantly altered by treatment.
Brookhaven National Laboratory; Evaluation of Micronuclei Frequency in the Peripheral Blood of Male and Female CD1 Mice
Exposed Chemically to Benzene for 90 Days, Final Report, (1985), EPA Document No. FYIAX10850393, Fiche No. OTS00003931
from HSDB
The levels of benzene and it's metabolites in the blood were evaluated in twenty male SpragueDawley rats and
eighty male Swiss albino mice receiving nominal concentration of benzene at 300ppm in a dynamic air flow chamber.
Sixteen mice and four rats were removed from the chamber after 1, 2, 4, 8 and 12 hours for eye bleeding. The mean
levels of benzene in the rat blood were < 1.0, 4.7, 4.8, 5.7, 5.3, and 7.1ppm at intervals of 0, 1, 2, 4, 8 and 12 hours
respectively. No free metabolites phenol, catechol & hydroquinone were detected at any of the time intervals in rats.
The mean levels of benzene in mouse blood were < 1.0, 3.7, 3.0, 2.4, 3.0 and 1.3ppm at intervals of 0, 1, 2, 4, 8 and 12
hours, respectively. The mean levels of free phenol in mouse blood were 2.0, 2.4, 2.2, 2.3, 2.5 and 2.3ppm at respective
intervals. No free catechol or hydroquinone were detected at any of the time intervals in mice. Also determined were
levels of conjugates in rat and mouse blood. The mean levels of conjugated phenol in rat blood were < 1.0, 3.0, 5.3,
4.2, 7.1 and 4.7ppm and the mean levels in the mouse blood were 2.7, 7.2, 8.7, 8.4, 9.1, and 3.7 at intervals 0, 1, 2, 4, 8
and 12 hours, respectively. No conjugated catechol or hydroquinone were detected at any of the time intervals in rats
or mice. It was concluded, that its takes approximately one hour to achieve a steady state level of benzene in rat and
mouse blood.
Bio/dynamics Inc.; Determination of Time to Steady State Level in Blood During Inhalation Exposure of Benzene to Rats and Mice,
(1980), EPA Document No. FYIAX02810104, Fiche No. OTS00001040
from HSDB
The levels of benzene and its's metabolites in blood were evaluated in male Sprague Dawley rats 4/group and male
Swiss albino mice 16/group receiving nominal concentrations of benzene at 0, 3, 30, 300 or 1000ppm in dynamic air
flow chamber for 6 hours. The mean levels of benzene in rat blood were < 1.0, < 1.0, < 1.0, 8.3 and 33.6ppm at
exposure levels 0, 3, 30, 300 and 1000ppm, respectively. No free metabolites phenol, catechol & hydroquinone were
detected at any exposure level in rat blood. The mean levels of benzene in the mouse blood were < 1.0, < 1.0, < 1.0,
1.44 and 29.5ppm at exposure levels 0, 3, 30, 300 and 1000ppm, respectively. A mean level of 1.2ppm of free phenol
was only detected at the high dose level in mice. No free catechol or hydroquinone were detected in mouse blood.
Also determined were the levels of conjugates in rat and mouse blood. The mean level of conjugated phenol in rat
blood were < 1.0, < 1.0, 1.7, 6.0 and 6.3ppm and the mean levels of conjugated phenol in mouse blood were < 1.0,
1.1, 2.9, 7.9 and 15.5ppm at exposure levels of 0, 30, 300 and 1000ppm, respectively. No conjugated catechol or
hydroquinone were detected at any exposure level in rats or mice. It was concluded that there was a direct correlation
between increased exposure to benzene and increased blood concentration levels of benzene and conjugated phenol.
Mice exposed to 1000ppm benzene had double the concentration of conjugated phenol in the blood relative to the
300ppm mice. In contrast, this effect was not observed in rats.
Bio/dynamics Inc.; Determination of Benzene, Phenol, Catechol and Hydroquinone in the Blood of Rats and Mice After Inhalation
Exposure to Benzene at Various Concentrations, (1980), EPA Document No. FYIAX02810104, Fiche No. OTS00001040
from HSDB
The concentration of benzene and it's metabolites were determined after 12, 24, 48 and 72 hours in the urine of five
exposed male Sprague Dawley rats and 25 male Swiss albino mice which received a nominal concentration of benzene
at 300ppm in dynamic air flow chamber for 6 hours. No level of benzene at or above the detection limit 1.0ppm
were detected in rat and mice urine at any of the sampling intervals. The level of free phenol in the rat urine were 2.0,
2.2, 1.7 and 3.2ppm and in mouse urine were 15.6, 4.7, 5.8 and 4.3ppm at 12, 24, 48 and 72 hours, respectively. The
mean levels of free catechol in rat urine were < 2.0, 0.46, 0.32 and < 2.0ppm and in mouse urine were 1.09, 1.29, 1.56
and 7.76ppm at 12, 24, 48 and 72 hours, respectively. No free hydroquinone at or above the detection limit were
determined in rat urine at any sampling time. The mean levels of free hydroquinone in mouse urine were 12.87, 1.49,
1.46 and 0.31ppm at 12, 24, 48 and 72 hours, respectively. The expired air of rats was bubbled through
dichloromethane and the mean total levels of benzene detected were 440.6, 101.4, not detected and 22.2ug/sampling
interval ending at 6, 12, 24 and 48 hours, respectively. Benzene in expired air of mice was only detected at the 48 hour
sampling interval.
Bio/dynamics Inc.; Part II: Determination of Material Balance in Rats, (1980), EPA Document No. FYIAX02810104, Fiche No.
OTS00001040
from HSDB
The in vitro percutaneous absorption of 14Cbenzene was evaluated in mammalian skin samples maintain in a
dynamic culture system. C3H Mice primary test subject, HRS mice, rabbit and guinea pig strain not specified dorsal
skin, and human skin from elective surgery were all placed in culture medium chamber for penetration analysis. 14C
Benzene 20ul was topically applied to cultured C3H mouse skin samples and radioactivity was detected in the
effluent medium 15 minutes following treatment with no apparent lag phase. Penetration was linear and the rates
were 2.97 +/ 0.03 and 3.70 +/ 0.03%/hr for metabolically viable fresh skin and nonviable skin frozen skin,
respectively. Analysis of the effluent medium indicated negligible conversion of benzene to phenol. Different rates of
in vitro skin permeation were observed between male and female C3H mice, however this difference was not
observed between sexes in similar studies with hairless HRS mice. In vitro penetration of benzene in hairless mice skin
2.44 +/ 0.07% was lower than C3H mice. Additional in vitro penetration studies with 14Cbenzene 20ul were
preformed with metabolically viable guinea pig, rabbit and human skin with rates of penetration of 0.04 +/ 0.01, 0.55
+/ 0.02 and 0.23 +/ 0.04%/hr, respectively. The lag phase of these additional studies were between 4560 minutes
and two hours from application followed by linear radioactivity. Toluene and unleaded gasoline containing 14C
benzene 20ul produced rates of permeation of 2.32 +/ 0.04 and 2.81 +/ 0.4%/hr, respectively in C3H mice which
appeared linear.
Oak Ridge National Laboratory; Toxicokinetics of Percutaneo us Penetration of Petroleum Products, Draft Final Report, (no date),
EPA Documen t No. FYIAX06850356, Fiche No. OTS00003561
from HSDB
The benzene uptake rate was evaluated in five male Sprague Dawley rats and twenty five male Swiss albino mice
receiving benzene at a nominal concentration of 300ppm in a dynamic air flow chamber for 6 hours. Five individual
rats were determined to have an internal mean benzene uptake rate of 152ml/min prior to conducting the six hour
test and an mean pretest respiratory minute volume of 145ml/min. The mean benzene uptake rates as compared to
pretest values for rats decreased to 33, 22 and 9% of the mean test value 1, 3 and 6 hours after administration,
respectively. The mean minute volume for rats decreased to 85, 78 and 66% of the pretest at 1, 3 and 6 hours after
administration, respectively. Rats had an estimated retained dose of 56mg/kg. Mice 5/group had a mean total
pretest benzene uptake rate of 188ml/min and a mean pretest total respiratory minute volume of 189ml/min. The
mean total benzene uptake for the mice decreased 65, 76 and 81% of the pretest value, after 1, 3 and 6 hours of
exposure, respectively. The mean total minute volume for groups of mice decreased 96, 84 and 69% of the pretest
after 1, 3 and 6 hours, respectively. The mean total retained dose per mice was estimated to be 377mg/kg.
Bio/dynamics Inc.; Part I: Determination of Benzene Uptake by the Lungs in Rats and Mice, Under Conditions of Prolonged Exposure,
(no date), EPA Document No. FYIAX02810104, Fiche No. OTS00001040
from HSDB
The dermal absorption of benzene vapor was examined in 2 Rhesus monkeys exposed to the test article at saturated
concentrations for 30 minutes using a hydration controlled chamber which was held tightly against the skin of the
back. The radioactivity measured in the urine was used to determined absorption rate. A correction factor was
included to account for radioactivity excreted by other routes. Under the 2 skin conditions, of 40% hydration and
100% hydration, the absorption rates were determined to be 0.02 microliter/sq cm and .15 microliter/sq cm,
respectively. Total absorption was found to be 7.5fold higher from a 100% relative humidity environment than from a
40% relative humidity environment. In a benzene liquid exposure experiment, the concentration of benzene was given
by its density of 0.8787 gm/cu cm and the dermal absorption was 5.4 microliter/sq cm. The authors suggested that
benzene absorption from the liquid state was less than expected due to a dehydrating effect on the stratum corneum.
American Petroleum Institute; Absorption of Petroleum Products Across the Skin of Monkey and Man, Final Report, (1987), EPA Doc.
No. FYIAX10870185, Fiche No. OTS00001851
from HSDB
13.1.28 Populations at Special Risk
... /It has been observed/ that levels of leukocyte agglutins were elevated in selected individuals exposed to benzene.
... /This/ suggested that in some people benzene toxicity may be accounted for in part by an allergic blood dyscrasia.
from HSDB
... Workers with higher activities of /cytochrome P4502E1/ are at more risk /of benzene hematoxicity/.
International Labour Office. Encyclopaedia of Occupational Health and Safety. 4th edition, Volumes 14 1998. Geneva, Switzerland:
International Labour Office, 1998., p. 1.2
from HSDB
... It has been suggested that Thalassemia minor, and presumably other disorders in which there is increased bone
marrow turnover, may predispose a person to benzeneinduced aplastic anemia.
International Labour Office. Encyclopaedia of Occupational Health and Safety. 4th edition, Volumes 14 1998. Geneva, Switzerland:
International Labour Office, 1998., p. 1.2
from HSDB
13.2 Ecological Information
13.2.1 ICSC Environmental Data
The substance is toxic to aquatic organisms. The substance may cause longterm effects in the aquatic environment.
from ILOICSC
13.2.2 Environmental Fate/Exposure Summary
Benzene's production, existence in gasoline, and use in the production of ethylbenzene and styrene as well as many
other chemicals may result in its release to the environment through various waste streams. Benzene is found in
volcanoes, as a constituent of crude oil, from forest fires, and as a plant volatile. If released to air, a vapor pressure of
94.8 mm Hg at 25 deg C indicates benzene will exist solely as a vapor in the ambient atmosphere. Vaporphase
benzene will be degraded in the atmosphere by reaction with photochemicallyproduced hydroxyl radicals; the half
life for this reaction in air is estimated to be 13 days. Vaporphase benzene is also degraded by ozone radicals and
nitrate found in the atmosphere but at such low rates as to not be important. A halflife of 16.9 days was reported for
photolysis of benzene dissolved in deionized water saturated with air exposed to sunlight. Since benzene is very water
soluble, it may be removed from the atmosphere by rain. If released to soil, benzene is expected to have high mobility
based upon a Koc of 85. Volatilization from moist soil surfaces is expected to be an important fate process based
upon a Henry's Law constant of 5.56X103 atmcu m/mole. Benzene may volatilize from dry soil surfaces based upon
its vapor pressure. Using a baserich parabrownish soil incubated for 10 weeks, 20 ppm benzene was 24% degraded
in 1 week, 44% in 5 weeks, and 47% in 10 weeks, indicating that biodegradation may be an important environmental
fate process in soil. If released into water, benzene is not expected to adsorb to sediment and suspended solids in
water based upon the Koc. Volatilization from water surfaces is expected to be an important fate process based upon
this compound's Henry's Law constant. Estimated volatilization halflives for a model river and model lake are 2.7 hrs
and 3.5 days, respectively. Utilizing the Japanese MITI test, 40% of the Theoretical BOD was reached in 2 weeks
indicating that biodegradation is important environmental fate process in water. In aqueous solution, benzene will
react with hydroxyl radical OH radical average concentration = 1.0X1017 molec/cu cm at a reaction rate of
7.8X10+9 L/mol sec which results in an estimated halflife of 103 days. A BCF ranging from 1.120 suggests
bioconcentration in aquatic organisms is low. Hydrolysis is not expected to occur due to the lack of hydrolyzable
functional groups. Occupational exposure to benzene may occur through inhalation and dermal contact with this
compound at workplaces where benzene is produced or used. Monitoring data indicate that the general population
may be exposed to benzene via inhalation of ambient air, ingestion of food and drinking water, and dermal and
inhalation contact with consumer products containing this compound. Benzene is a component of cigarette smoke
and is widely detected in atmospheric samples due to its presence in gasoline. SRC
from HSDB
13.2.3 Natural Occurring Sources
... Benzene has been reported to be a natural constituent of fruits, vegetables, meats, and dairy products with
concentrations ranging from 2 ug/kg in canned beef to 2100 ug/kg for eggs.
Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials ToxicologyClinical Principles of Environmental Health. Baltimore, MD:
Williams and Wilkins, 1992., p. 724
from HSDB
Benzene is found naturally in the environment from volcanoes, as a natural constituent of crude oil, from forest fires
and as a plant volatile1,2. Benzene concentrations range from 100200 parts per trillion over the Pacific and Atlantic
Oceans due to seepage and spillage of oil into the oceans3.
(1) IARC; Monograph. Some Industrial Chemicals and Dyestuffs 29: 99106 (1982) (2) Graedel TE; Chemical Cmpds in the Atmos.
NY, NY: Academic Press (1978) (3) Singh HB, Zimmerman PB; Adv Environ Sci Technol 24: 177235 (1992)
from HSDB
13.2.4 Artificial Sources
Benzene's production and use in the manufacture of industrial chemicals such as polymers, detergents, pesticides,
pharmaceuticals, dyes, plastics, resins, as an organic solvent for waxes, resins, oils, natural rubber, etc, a reference for
quantitating compounds, and as a gasoline additive1 may result in its release to the environment through various
waste streamsSRC.
(1) O'Neil MJ, ed; The Merck Index. 15th ed., Cambridge, UK: Royal Society of Chemistry, p. 188 (2013)
from HSDB
Benzene enters the environment from production, storage, transport, venting, and combustion of gasoline; and from
production, storage, and transport of benzene itself. Other sources result from its use as an intermediate in the
production of other chemicals, and as a solvent, from spills, including oil spills; from its indirect production in coke
ovens; from nonferrous metal manufacture, ore mining, wood processing, coal mining and textile manufacture, and
from cigarette smoke1,2.
(1) IARC; Monograph. Some Industrial Chemicals and Dyestuffs 29: 99106 (1982) (2) Graedel TE; Chemical Cmpds in the Atmos,
New York, NY: Academic Press (1978)
from HSDB
Benzene is the largest volume aromatic petrochemical; ethylbenzene is the largest chemical outlet for benzene, and
nearly all is consumed for the production of styrene1. Benzene has been detected in cigarette smoke ranging from
4764 ppm2. The world wide release of benzene into the environment is estimated to be 45 Tg/yr with 0.6 Tg/yr
coming from the United States alone3. Leachate from landfills is also a source of benzene in the environment4.
(1) ICIS Chemical Business; US Chemical Profile Benzene. 25 Feb 3 Mar 2013. Available from, as of Feb 20, 2014:
http://www.icis.com (2) Clayton GD, Clayton FE; Patty's Industrial Hygiene And Toxicology, 4th ed., New York, NY: John Wiley &
Sons, Vol IIB p. 1302 (1994) (3) Singh HB, Zimmerman PB; Adv Environ Sci Technol 24: 177235 (1992) (4) Johnston JJ et al; J
Contam Hydrol 23: 263283 (1996)
from HSDB
13.2.5 Environmental Fate
TERRESTRIAL FATE: Based on a classification scheme1, a Koc value of 852, indicates that benzene is expected to
have high mobility in soilSRC. Volatilization of benzene from moist soil surfaces is expected to be an important fate
processSRC given a Henry's Law constant of 5.56X103 atmcu m/mole3. The potential for volatilization of benzene
from dry soil surfaces may existSRC based upon a vapor pressure of 94.8 mm Hg4. Using a baserich parabrownish
soil incubated for 10 weeks, 20 ppm benzene was 24% degraded in 1 week, 44% in 5 weeks, and 47% in 10 weeks5,
indicating that biodegradation may be an important environmental fate process in soilSRC. Anaerobic degradation
of benzene in soil is not expected to be an important loss process based on various studies6,7. In one study of
chemical biotransformation under nitrate and sulfatereducing conditions, benzene was found to be stable for 60
days6. In a related study, benzene did not undergo biodegradation in situ nor in laboratory controlled soil samples
under denitrifying conditions7.
(1) Swann RL et al; Res Rev 85: 1728 (1983) (2) Hodson J, Williams NA; Chemosphere 17: 6777 (1988) (3) Mackay D et al; Environ
Sci Tech 13: 33336 (1979) (4) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals: Data
Compilation. Design Inst Phys Prop Data, Amer Inst Chem Eng New York, NY: Hemisphere Pub Corp 5 Vol (1989) (5) Haider K et al;
Arch Microbiol 96: 183200 (1974) (6) Reinhard M et al; Div Environ Chem Preprints Ext Abst 36: 210212 (1996) (7) Hutchins SR,
Wilson JT; pp. 15772 in In Situ Bioreclamation. Hinchee RE, Olfenbuttel RF, eds. Stoneham, MA: ButterworthHeinmann (1991)
from HSDB
AQUATIC FATE: Based on a classification scheme1, a Koc value of 852, indicates that benzene is not expected to
adsorb to sediment and suspended solids in waterSRC. Volatilization from water surfaces is expected3 based upon
a Henry's Law constant of 5.56X103 atmcu m/mole4. Using this Henry's Law constant and an estimation method3,
volatilization halflives for a model river and model lake are 1 hr and 3.5 days, respectivelySRC. In aqueous solution,
benzene will react with hydroxyl radical at a reaction rate of 7.8X10+9 L/mol sec; using the average OH radical
concentration 1.0X1017 molec/cu cm, benzene would have a halflife of 103 days5. According to a classification
scheme6, BCFs ranging from 1.1207 suggests the potential for bioconcentration in aquatic organisms is low.
Utilizing the Japanese MITI test, 40% of the Theoretical BOD was reached in 2 weeks8 indicating that biodegradation
is important environmental fate process in waterSRC. Anaerobic degradation of benzene in water is not expected to
be an important loss process based on various studies9. In one study of chemical biotransformation under nitrate
and sulfatereducing conditions, benzene was found to be stable for 60 days5.
(1) Swann RL et al; Res Rev 85: 1728 (1983) (2) Hodson J, Williams NA; Chemosphere 17: 6777 (1988) (3) Lyman WJ et al;
Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 49, 151 to 1529 (1990) (4) Mackay D
et al; Environ Sci Tech 13: 33336 (1979) (5) Buxton GV et al; J Phys Chem Ref Data 17: 513882 (1988) (6) Franke C et al;
Chemosphere 29: 150114 (1994) (7) Neff JM, Sauer TC; Environ Sci Res 53: 16375 (1996) (8) NITE; Chemical Risk Information
Platform (CHRIP). Biodegradation and Bioconcentration. Tokyo, Japan: Natl Inst Tech Eval. Available from, as of Feb 18, 2014:
http://www.safe.nite.go.jp/english/db.html (9) Reinhard M et al; Div Environ Chem Preprints Ext Abst 36: 210212 (1996)
from HSDB
AQUATIC FATE: Evaporation was the primary loss mechanism in winter in a mesocosm experiment which simulated a
northern bay where the halflife was 13 days1. In spring and summer the halflives were 23 and 3.1 days,
respectively1. In these cases biodegradation plays a major role and takes about 2 days1. However, acclimation is
critical and this takes much longer in the colder water in spring1. According to one experiment, benzene has a half
life of 17 days due to photochemical degradation2 which could contribute to benzene's removal. In situations of
cold water, poor nutrients, or other conditions less conducive to microbial growth, photolysis will play a important
role in degradationSRC. The halflife of benzene in sea water is about 5 hrs3 based on its Henry's Law constant of
5.56X103 atmcu m/mole4. The average firstorder rate constant for elimination of benzene in the epilimnion
region of Lake Zurich, Switzerland during summer boating season is 0.080/day5.
(1) Wakeham SG et al; Bull Environ Contam Toxicol 31: 5824 (1983) (2) Hustert K et al; Chemosphere 10: 9958 (1981) (3) Neff JM,
Sauer TC; Environ Sci Res 53: 16375 (1996) (4) Mackay D et al; Environ Sci Tech 13: 33336 (1979) (5) Schmidt TC et al; Water Res
38: 15201529 (2004)
from HSDB
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the
atmosphere1, benzene, which has a vapor pressure of 94.8 mm Hg at 25 deg C2, is expected to exist solely as a
vapor in the ambient atmosphere. Vaporphase benzene is degraded in the atmosphere by reaction with
photochemicallyproduced hydroxyl radicalsSRC; the halflife for this reaction in air is estimated to be 13 daysSRC,
calculated from its rate constant of 1.23X1012 cu cm/moleculesec at 25 deg C3. The halflife in polluted
atmospheres which contain nitrogen oxides or sulfur dioxide has been observed to shorten to 46 hrs4. Vaporphase
benzene is also degraded in the atmosphere by atmospheric ozone radicals at an extremely slow rate; the halflife for
this reaction in air is estimated to be 170,000 days5. The reaction rate of benzene with nitrate radical in the
atmosphere is estimated to be less than 0.3X1016 cu cm/molecule sec at 25 deg C3; the halflife for this reaction in
air is estimated to be greater than or equal to 111 days based on an average concentration of nitrate radicals of
2.4X10+8 molec/cu cm6. A halflife of 16.9 days was reported for photolysis of benzene dissolved in deionized water
saturated with air exposed to sunlight7. Due to benzene's high water solubility, it may be removed from the
atmosphere by rainfall8.
(1) Bidleman TF; Environ Sci Technol 22: 361367 (1988) (2) Daubert TE, Danner RP; Physical and Thermodynamic Properties of
Pure Chemicals: Data Compilation. Design Inst Phys Prop Data, Amer Inst Chem Eng New York, NY: Hemisphere Pub Corp 5 Vol
(1989) (3) Atkinson R; J Phys Chem Ref Data, Monograph No. 2 (1994) (4) Korte F, Klein W; Ecotox Environ Safety 6: 31127 (1982)
(5) Verschueren K; Handbook of Environmental Data on Organic Chemicals. 4th ed. New York, NY: Van Nostrand Reinhold pg. 255
(2001) (6) Atkinson, R et al; Atmos Env 24: 264754 (1990) (7) Hustert K et al; Chemosphere 10: 9958 (1981) (8) May WE et al; J
Chem Ref Data 28: 197200 (1983)
from HSDB
13.2.6 Biodegredation
AEROBIC: Benzene present at 100 mg/L, reached 40% of its theoretical BOD in 2 weeks using an activated sludge
inoculum at 30 mg/L in the Japanese MITI test1. Benzene reached 24% of its theoretical oxygen demand in a non
acclimated microbial population after 15 days2. Aerobic biodegradation of benzene was studied in preequilibrated
soilwater slurry microcosms3. Using an enriched aerobic bacterial culture, benzene began to degrade 12 hrs after
incubation in an aqueoussoilfree solution with 50% of benzene degrading after 60 hrs and almost complete
degradation within 90 hrs. Using a preequilibrated soilwater slurry microcosm, benzene did not begin to degrade
until 3 days after application and reached complete degradation after about 12 days3.
(1) NITE; Chemical Risk Information Platform (CHRIP). Biodegradation and Bioconcentration. Tokyo, Japan: Natl Inst Tech Eval.
Available from, as of Feb 18, 2014: http://www.safe.nite.go.jp/english/db.html (2) Verschueren K; Handbook of Environmental Data
on Organic Chemicals. 4th ed. New York, NY: Van Nostrand Reinhold pg. 255 (2001) (3) Zhang WX, Bouwer EJ; Biodegradation 8:
167175 (1997)
from HSDB
AEROBIC: No degradation of benzene as measured by BOD was reported in coarsefiltered through 1 cm cotton
layer Superior harbor water incubated at 21 deg C for 12 days1. Biodegradation halflives of 28 and 16 days were
reported in dieaway tests using groundwater and water from Lester River, Minnesota, respectively; benzene
concentration added ranged from 03.2 mg/L2. The halflife in estuarine water was 6 days as measured by radio
labeled C02 produced3. In a marine ecosystem biodegradation occurred in 2 days after an acclimation period of 2
days and 2 weeks in the summer and spring, respectively, whereas no degradation occurred in winter4.
(1) Vaishnav DD, Babeu L; J Great Lakes Res 12: 18491 (1986) (2) Vaishnav DD, Babeu L; Bull Environ Contam Toxicol 39: 23744
(1987) (3) Lee RF, Ryan C; Microbial Degradation of Pollutants in Marine Environments. pp. 44350 USEPA600/972012 (1979) (4)
Wakeman SG et al; Bull Environ Contam Toxicol 31: 5824 (1983)
from HSDB
AEROBIC: Benzene, in a mixture with toluene and xylenes, was readily biodegraded total degradation of 7.5 ppm total
mixture in shallow ground water in the presence of oxygen in the unconfined sand aquifer at Canada Forces' Base
Borden, Ontario; laboratory batch experiments demonstrated that the degradation could be attributed to
biodegradation1. Complete biodegradation in 16 days was reported under simulated aerobic groundwater
conditions at 20 deg C2. Reported metabolites of benzene using pure cultures of microorganisms include phenol
and unidentified phenols3, catechol and cis1,2dihydroxy1,2dihydrobenzene4.
(1) Barker JF et al; Ground Water Monit Rev 7: 6472 (1987) (2) Delfino JJ, Miles CJ; Soil Crop Sci Soc FL Proc 44: 914 (1985) (3)
Smith RV, Rosazza SP; Arch Biochem Biophys 161: 5518 (1974) (4) Gibson DT et al; Biochem 7: 265362 (1968)
from HSDB
AEROBIC: Benzene at 50 ppm was 90% degraded by industrial wastewater seed incubated at 23 deg C for 6 hrs1.
Benzene inhibited industrial seed at concentration of 100 ppm and above and municipal seed at 50 ppm and
above1. In a bench scale activatedsludge reactor with an 8 hour retention time, complete degradation occurred
with 0.5% of the benzene being lost by air stripping2. In laboratory systems, low concentrations of benzene are
degraded in 614 days3,4. 44100% removal occurred at a sewage treatment plant; percentage by evaporation and
biodegradation were not determined5. In a baserich parabrownish soil, 20 ppm benzene was 24% degraded in 1
week, 44% in 5 weeks, and 47% in 10 weeks6.
(1) Davis EM et al; Water Res 15: 11257 (1981) (2) Stover EL, Kincannon DF; J Water Pollut Control Fed 55: 97109 (1983) (3)
Setzkorn EA, Huddleston RL; J Amer Oil Chem Soc 42: 10814 (1965) (4) Tabak HH et al; J Water Pollut Control Fed 53: 150318
(1981) (5) Feiler HD et al; Proc Natl Conf Munic Sludge Manag 8th, pp. 7281 (1979) (6) Haider K et al; Arch Microbiol 96: 183200
(1974)
from HSDB
ANAEROBIC: Benzene was degraded under methanogenic conditions in an enrichment culture fed ferulic acid for five
years. It was also degraded under sulfatereducing conditions in microcosms containing benzenecontaminated
aquifer sediment1. Benzene was not biodegraded in aquifer sediment down gradient of the Wilder's Grove sanitary
landfill near Raleigh, NC1. In a study of chemical biotransformation under nitrate and sulfatereducing conditions,
benzene was found to be stable under these anaerobic conditions for 60 days2. In a related study, benzene did not
undergo biodegradation in situ nor in laboratory controlled soil samples under denitrifying conditions3. Although
benzene appears to be recalcitrant under anaerobic conditions, there was one experiment in which benzene
underwent degradation under methanogenic conditions. The microbial inoculum employed in the study originally had
been enriched from anaerobic municipal sludge. Benzene was transformed into phenol by the microbial inoculum by
using water as a source of oxygen4.
(1) Johnston JJ et al; J Contam Hydrol 23: 263283 (1996) (2) Reinhard M et al; Div Environ Chem Preprints Ext Abst 36: 210212
(1996) (3) Hutchins SR, Wilson JT; pp. 15772 in In Situ Bioreclamation. Hinchee RE, Olfenbuttel RF eds. Stoneham, MA: Butterworth
Heinmann (1991) (4) GrbicGalic, D; Geomicrobiology J 8: 167200 (1990)
from HSDB
13.2.7 Abiotic Degredation
The rate constant for the vaporphase reaction of benzene with photochemicallyproduced hydroxyl radicals is
1.23X1012 cu cm/moleculesec1. This corresponds to an atmospheric halflife of about 13 days at an atmospheric
concentration of 5X10+5 hydroxyl radicals per cu cm1. The halflife in polluted atmospheres which contain nitrogen
oxides or sulfur dioxide has been observed to shorten to 46 hrs2. Vapor phase benzene is also degraded in the
atmosphere by atmospheric ozone radicals at an extremely slow rate; the halflife for this reaction in air is estimated
to be 170,000 days3. Reaction of benzene with nitrate radical is estimated to be <0.3X1016 cu cm/molecule sec at
25 deg C1; the halflife for this reaction in air is estimated to be greater than or equal to 111 days based on an
average concentration of nitrate radicals of 2.4X10+8 molec/cu cm in the ambient atmosphere4. In aqueous
solution, benzene will react with hydroxyl radical at a reaction rate of 7.8X10+9 L/mol sec; using the average OH
radical concentration1.0X1017 molec/cu cm, benzene would have a halflife of 103 days5. Benzene is not expected
to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups6. Benzene has a
maximum absorbance frequency of 253 nm7 and, therefore, is not expected to be susceptible to direct photolysis by
sunlightSRC. However, slight shifts in wavelength of absorption might be expected in more representative
environmental media, such as water8; eg, a halflife of 16.9 days was reported for photolysis of benzene dissolved in
deionized water saturated with air exposed to sunlight9.
(1) Atkinson R; J Phys Chem Ref Data Mongraph No. 2 p. 48 (1994) (2) Korte F, Klein W; Ecotox Environ Safety 6: 31127 (1982) (3)
Verschueren K; Handbook of Environmental Data on Organic Chemicals. 4 th ed. New York, NY: Van Nostrand Reinhold pg. 255
(2001) (4) Atkinson, R et al; Atmos Env 24: 264754 (1990) (5) Buxton GV et al; J Phys Chem Ref Data 17: 513882 (1988) (6) Lyman
WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 74, 75 (1990) (7) Trost B et al;
Atmos Environ 31: 39994008 (1997) (8) Howard PH, Durkin PR; Sources of Contamination, Ambient Levels, and Fate of Benzene in
the Environment. USEPA560/575005 pp. 65 (1974) (9) Hustert K et al; Chemosphere 10: 9958 (1981)
from HSDB
While benzene is considered to be relatively unreactive in photochemical smog situations in the presence of nitrogen
oxides, its rate of degradation is accelerated with about 16% decrease in concentration in 5 hr1. A typical
experiment in the presence of active species such as NOx and SO2 showed that benzene photodegradation was
considerably accelerated above that in air alone2. Its halflife in the presence of active species was 46 hr with 50%
mineralization to CO2 in approximately 2 days3. Products of degradation include phenol, 2nitrophenol, 4
nitrophenol, 2,4dinitrophenol, 2,6dinitrophenol, nitrobenzene, formic acid, and peroxyacetyl nitrate46. Benzene
has an estimated lifetime under photochemical smog conditions in southeastern England of 28 hrs3. Benzene has an
estimated global lifetime of 16 days and 4.8 days in the tropics7. Global conditions were considered as having an
average temperature of 2 deg C, OH radical concentration of 6.0X10+5 molecule/cu cm and an ozone radical
concentration of 7.4X10+11 molecule/cu cm; while tropical conditions were considered as having an average
temperature of 25 deg C, OH radical concentration of 2.0X10+6 molecule/cu cm and an ozone radical concentration
of 7.4X10+11 molecule/cu cm7.
(1) Farley FF; Inter Conf on Photochemical Oxidant Pollution and Its Control. pp. 71327 USEPA600/377001B (1977) (2)
Yanagihara S et al; Proc Int Clean Air Cong 4th, pp. 4727 (1977) (3) Korte F, Klein W; Ecotox Environ Saftey 6: 31127 (1982) (4)
Nojima K et al; Chemosphere 4: 7782 (1975) (5) Hoshino M et al; Kokuritsu Kogai Kekyusho Kenkyu Hokoku 5: 4359 (1978) (6)
Kopczynski SL; Int J Air Water Pollut 8: 10720 (1964) (7) Singh HB, Zimmerman PB; Adv Environ Sci Technol 24: 177235 (1992)
from HSDB
13.2.8 Bioconcentration
Benzene has BCFs ranging from 1.1201. According to a classification scheme2, this BCF range suggests the
potential for bioconcentration in aquatic organisms is low. The uptake and elimination rate constants for benzene in
fathead minnows were studied3. Fathead minnows were found to have an average uptake rate of 7 L/kg/hr with an
average elimination rate of 0.384/hr which corresponds to a BCF of 193. In a study of BCF values for various aquatic
species, benzene was found to have a BCF value of 3.5 in eels4, 4.4 in pacific herring5, and 4.3 in goldfish6.
(1) Neff JM, Sauer TC; Environ Sci Res 53: 16375 (1996) (2) Franke C et al; Chemosphere 29: 150114 (1994) (3) De Wolf W et al;
Chemosphere 36: 17131724 (1998) (4) Ogata M, Miyake Y; Water Res 12: 10414 (1978) (5) Korn S et al; Fish Bull Natl Marine Fish
Ser 75: 6336 (1977) (6) Ogata M et al; Bull Environ Contam Toxicol 33: 5617 (1984)
from HSDB
13.2.9 Soil Adsorption/Mobility
An experimentally derived log Koc of 1.93 Koc = 85 was obtained via reverse phase HPLC high performance liquid
chromatography with a cyanopropyl column and a mobile phase of water1. According to a classification scheme2,
this estimated Koc value suggests that benzene is expected to have high mobility in soil. The sorption equilibrium for
benzene in a soil/water mixture ratio soil/water 0.12 kg/l took 72 hrs3. The Koc for benzene has also been
experimentally determined to be 794.
(1) Hodson J, Williams, NA; Chemosphere 17: 6777 (1988) (2) Swann RL et al; Res Rev 85: 1728 (1983) (3) Zhang WX, Bouwer EJ;
Biodegradation 8: 167175 (1997) (4) Johnston CD et al; J Cont Hydrol 33: 377404 (1998)
from HSDB
13.2.10 Volatilization from Water/Soil
The Henry's Law constant for benzene is 5.56X103 atmcu m/mole1. This Henry's Law constant indicates that
benzene is expected to volatilize rapidly from water surfaces2. Based on this Henry's Law constant, the volatilization
halflife from a model river 1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec2 is estimated as 1 hrSRC. The
volatilization halflife from a model lake 1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec2 is estimated as
3.5 daysSRC. Benzene's Henry's Law constant1 indicates that volatilization from moist soil surfaces may occurSRC.
The potential for volatilization of benzene from dry soil surfaces may existSRC based upon a vapor pressure of 94.8
mm Hg3.
(1) Mackay D et al; Environ Sci Technol 13: 33336 (1979) (2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods.
Washington, DC: Amer Chem Soc pp. 151 to 1529 (1990) (3) Daubert TE, Danner RP; Physical and Thermodynamic Properties of
Pure Chemicals: Data Compilation. Design Inst Phys Prop Data, Amer Inst Chem Eng New York, NY: Hemisphere Pub Corp 5 Vol
(1989)
from HSDB
13.2.11 Water Concentrations
GROUNDWATER: Benzene was the dominant dissolved organic compound in groundwater contaminated by gasoline
in the Swan Coastal Plain near Perth, Western Australia at a concentration around 15,000 ug/L at depths greater than
4.5 m below ground surface1. At a distance of 210 m from a petrol storage area, a chalk aquifer, located in the
United Kingdom, contained benzene ranging from 110 ppb; at 120 m from the petrol storage area it contained
benzene concentrations greater than 250 ppb; and at 10 m from the petrol storage area, benzene concentrations rose
to 1250 ppb2. Benzene occurs in both groundwater and surface public water supplies with higher levels occurring in
groundwater supplies. Based upon U.S. Federal drinking water surveys, approximately 1.3% of all groundwater
systems are estimated to contain benzene at levels greater than 0.5 ug/L. The highest level reported in the surveys for
groundwater was 80 ug/L3.
(1) Johnston CD et al; J Contam Hydrol 33: 377404 (1998) (2) Tester DJ, Harker RJ; Water Pollut Control 80: 61431 (1981) (3)
USEPA; Health Advisories for 25 Organics: Benzene p. 19 (1987)
from HSDB
DRINKING WATER: Out of 113 public drinking water supplies in 1976, 7 sites tested positive for benzene with an
average concentration of <0.2 ppb1. Of five US cities from 19745, benzene concentrations ranged from 00.3 ppb in
drinking water supplies2. Contaminated drinking water wells in NY, NJ, and CT ranged from 30300 ppb; the highest
benzene concentrations in drinking water were derived from surface water sources at 4.4 ppb3. In three separate
surveys of community water supplies: 0 of 111 samples tested positive for benzene; 7 of 113 samples tested positive
with a mean concentration of 4 ppb; and 4 of 16 samples tested positive with a benzene max concentration of 0.95
ppb4. In a USA Groundwater Supply Survey GWS, 1982, finished drinking water, out of 466 samples selected at
random from a 1000 sample survey, 0.6% tested positive for benzene at a median value of 3 ppb and max of 15
ppb5. In a study of Wisconsin drinking water wells data through Jun 1984, of 1174 community wells sampled,
0.34% tested positive for benzene while of 617 private wells, 2.9% tested positive6.
(1) Brass HJ et al; Drinking Water Qual Enhancement Source Prot pp. 393416 (1977) (2) Coleman WE et al; pp. 30527 in Analysis
and Identification of Organic Substances in Water. L Keith ed, Ann Arbor MI: Ann Arbor Press Chap 21 (1976) (3) Burmaster DE;
Environ 24: 613,336 (1982) (4) NAS; Drinking Water and Health, Vol 3 (1980) (5) Cotruvo JA; Sci Total Environ 47: 726 (1985) (6)
Krill RM, Sonzogni WC; J Am Water Works Assoc 78: 705 (1986)
from HSDB
DRINKING WATER: There may be a large number of cases where well water is contaminated by benzene at low
concentrations1. A number of studies have reported finding benzene at levels on the order of 5 ng/L in surface and
well waters1. Benzene had a frequency of detection of less than 1% in 954 random drinking water sources samples
from groundwater, rivers, and reservoirs throughout the USA and Puerto Rico from May 3, 1999 through Oct 23,
20002. A 2006 US Geol Survey of 2,401 domestic wells sampled from 19852002 revealed occurrence of benzene in
37 of 1,207 wells, a 3.1% detection frequency. The concentration range was 0.0065 ug/L3. The detection frequency
in drinking water sources from California was <1% from 1995 to 20014.[1 Wallace L; Environ Health Perspect 104:
11291136 1996 2 Grady SJ; A National Survey of methyl tertbutyl ether and other volatile organic compounds in
drinkingwater sources. US Dept Int, U.S. Geological Survey, WaterResources Investigations Report 024079 2003 3
Rowe BL et al; Environ Health Perspect 11511: 15391546 2007 4 Williams P et al; Environ Sci Technol 36:4 721
4728 2002] Full text: PMC1469757 Abstract: PubMed
from HSDB
SURFACE WATER: Surface water samples taken from 14 heavily industrialized areas with water basins between 1975
1976, contained benzene in 20% of the samples at concentrations ranging from 17 ppb1. Benzene concentrations in
Lake Erie from 19756, ranged from 01 ppb2. Benzene concentrations in Lake Michigan from 19756, ranged from
07 ppb2. Out of 700 random surface water sites throughout the US in 1975, benzene had an average concentration
of 5.4 ppb3. In the US EPA STORET database, out of 1,271 surface water samples, 15.0% tested positive for benzene
with a median concentration of 5.0 ppb4. Benzene concentrations in seawater taken from the Gulf of Mexico in 1977,
ranged from 515 parts per trillion in unpolluted areas and 5175 parts per trillion in areas affected by anthropogenic
activities5. Approximately 3% of all surface water drinking systems are estimated to be contaminated at levels higher
than 0.5 ug/L6.
(1) Ewing BB et al; Monitoring to Detect Previously Unrecognized Pollutants in Surface Waters. USEPA560/677015 pp. 75 (1977)
(2) Konasewich D et al; Great Lake Water Qual Board (1978) (3) Kraybill HF; NY Acad Sci Annals 298: 809 (1977) (4) Staples CA et
al; Environ Toxicol Chem 4: 13142 (1985) (5) Sauer TC Jr; Org Geochem 3: 91101 (1981) (6) USEPA; Health Advisories for 25
Organics: Benzene p. 19 (1987)
from HSDB
RAIN/SNOW/FOG: Benzene was detected in rainwater in Japan and in the UK at a concentration of 87.2 ppb1,2.
(1) Kato T et al; Yokohama Kokuritsu Daigaku Kankyo Kagaku Kenkyu Senta Kiyo 6: 1120 (1980) (2) IARC; Monograph. Some
Industrial Chemicals and Dyestuffs. 29: 99106 (1982)
from HSDB
13.2.12 Effluents Concentrations
Industries in which mean or max levels of benzene in raw wastewater exceeded 1 ppm are number of samples,
percent pos, mean, max, in ppm: raw wastewater: auto and other laundries 20 samples, 70% pos, <1.4 ppm mean, 23
ppm max, iron and steel manufacturing mfg 9 samples, 77.8% pos, <8.0 mean, 46 max, aluminum forming 32
samples, 56.2% pos, 0.70 mean, 2.1 max, photographic equipment/supplies 48 samples, 54.2% pos, 0.16 mean, 2.1
max, pharmaceutical mfg 9 samples, 100% pos, 12 mean, 87 max, organic chemical/plastics mfg number of samples
not reported NR, 63 detections, 22, NR, paint and ink formulation 36 samples, 63.9% pos, 1.2 mean, 9.9 max,
petroleum refining 11 samples, number of pos NR, <0.10, 2.4, rubber processing 4 samples, 100% pos, 0.60 mean,
3.4 max, timber products processing 14 samples, 92.9% pos, 0.2 mean, 2.8 max; treated wastewater: auto and other
laundries 4 samples, 50% pos, 0.1 ppm mean, 0.2 ppm max, iron and steel manufacturing mfg 13 samples, 76.9%
pos, <14 mean, 120 max, aluminum forming 21 samples, 81.0% pos, <0.0058 mean, 0.040 max, photographic
equipment/supplies 4 samples, 100% pos, 0.016 mean, 0.021 max, pharmaceutical mfg 6 samples, 100% pos, 1.8
mean, 10 max, organic chemical/plastics mfg number of samples not reported NR, 42 detections, 26, max NR,
paint and ink formulation 24 samples, 62.5% pos, 0.39 mean, 3.8 max, petroleum refining 13 samples, NR, NR,
0.012, rubber processing 5 samples, 100% pos, <0.0077 mean, 0.010 max, timber products processing 5 samples,
60% pos, 0.010 mean, 0.033 max1.
(1) USEPA; Treatability Manual. p. I.9.11 to I.9.15 USEPA600/282001A (1981)
from HSDB
Wastewater from coal preparation plants ranged from 0.348 ppb while wastewater from plants which manufacture or
use benzene ranged from <1179 parts per trillion1. Stack emissions from coking plants located in Czechoslovakia
contained benzene ranging from 1550 ppm2. In 11.2% of groundwater samples taken from 178 CERCLA hazardous
waste sites, benzene was detected3. In the US EPA STORET database, out of 1,474 effluent samples, 16.4% tested
positive for benzene at a median concn of 2.50 ppb4.
(1) IARC; Monograph. Some Industrial Chemicals and Dyestuffs 29: 99106 (1982) (2) SRI; Human Exposure to Atmospheric Benzene,
Menlo Park, CA: SRI, Center for Resource and Environmental (1977) (3) Plumb H Jr; Ground Water Monit Rev 7: 94100 (1987) (4)
Staples CA et al; Environ Toxicol Chem 4: 13142 (1985)
from HSDB
In 4 municipal landfill gases in Southern Finland 19891990 data, benzene's average concentration ranged from
0.179 mg/cu m with a max concentration of 11 mg/cu m1. Benzene emissions were studied from seven Swedish
incineration plants before and after air pollution control systems APCS were introduced2. Benzene concentrations
emitted from plant A 3 incinerators without APCS were 1.93, 1.95, and 21.16 ug/cu nm and with APCS were 2.46, 0.83
and 1.81 ug/cu nm, respectively. Plant B 3 incinerators benzene levels were 21.23, 10.81, and 1.63 ug/cu nm before
APCS and 14.37, 444.20, and 0.14 ug/cu nm after APCS, respectively2. Oddly, benzene levels rose on an incinerator
after APCS. At the third plant, benzene concentrations were 2.57 ug/cu nm before APCS and 0.79 ug/cu nm after
APCS2. At the fourth plant, benzene concentrations were 3.44 ug/cu nm before APCS and 1.32 ug/cu nm after
APCS2. At the fifth plant, benzene concentrations were 0.82 ug/cu nm before APCS and 0.37 ug/cu nm after APCS2.
At the sixth plant, benzene concentrations were 2.92 ug/cu nm before APCS and 1.64 ug/cu nm after APCS2. At the
seventh plant 3 incinerators benzene concentrations were 4.31, 8.30 and 5.13 ug/cu nm before APCS and 1.49, 1.02,
and 11.36 ug/cu nm after APCS, respectively2. The amount of benzene in the gaseous emissions of medical waste
incinerator in 1000bed hospitals in Portugal ranged from 0.73 to 1.1 kg/yr3. Benzene emission factors of 2954
tons/yr were estimated from a large steel factory in Taranto, Italy, measured in November, December 2001 and May
20024.
(2001) (2) Zhang XJ; J Environ Sci Health A33: 279306 (1998) (3) Alvim Ferraz MCM et al; J Air Waste Manage Assoc 50: 13136
(2000) (4) Liberti L et al; J Air Waste Manage Assoc 56: 225260 (2005)
from HSDB
13.2.13 Sediment/Soil Concentrations
SEDIMENT: Surface sediments taken from Walvis Bay off Capetown, South Africa contained benzene ranging from 0
20 ppb1. In the US EPA STORET database, out of 355 samples, 9% tested positive for benzene at a median
concentration of <5.0 ppb2.
(1) Whelan JK et al; Geochim Cosmochim Acta 44: 176785 (1980) (2) Staples CA et al; Environ Toxicol Chem 4: 13142 (1985)
from HSDB
SOIL: Soil near factories where benzene was used or produced contained benzene ranging from 2191 ug/kg1.
(1) IARC; Monograph. Some Industrial Chemicals and Dyestuffs 29: 99106 (1982)
from HSDB
13.2.14 Atmospheric Concentrations
URBAN/SUBURBAN: Benzene concentrations in 20012003 exhibited an overall reduction of 60% from previous
testing in 19902003 but were still above the health risk threshold1.
Statistic Lakawana Brooklyn Troy Niagara Falls
19902003
Mean 5.09 2.85 2.31 1.80
Median 3.09 2.33 1.88 1.26
Max 104.51 15.23 17.57 21.87
20012003
Mean 2.26 2.05 1.68 1.08
Median 1.35 1.81 1.39 0.92
Max 16.71 7.52 6.91 4.10
(1) Aleksic N et al; Atmos Environ 39: 78947905 (2005)
from HSDB
URBAN/SUBURBAN: Air samples taken in the US from 19771980, had an average benzene concentration of 2.8 ppb
in 2292 samples1. Average benzene concentrations were 13 ppb 98 ppb max in Toronto, Canada 19712. Average
benzene concentrations in Los Angeles, California 1966 averaged 15 ppb 57 ppb max2. In 24 hr sampling periods
conducted in US cities in 1979, benzene concentrations in Los Angeles, CA in April ranged from 0.7227.87 ppbmean
6.04 ppb, in Phoenix, AZ from AprilMay benzene ranged from 0.3959.89 ppb mean 4.74 ppb, in Oakland, CA from
JuneJuly benzene ranged from 0.064.63 ppb mean 1.55 ppb3. Atmospheric benzene concentrations were studied
in New Jersey in 1978 with the following cities reporting detections: Rutherford, 149 samples, 3.8 ppb mean
concentration with 107 ppb max; Newark, 110 samples, 2.6 ppb mean concentration with 24 ppb max;
Piscataway/Middlesex, 18 samples, 1.0 ppb mean concentration with 1.9 ppb max; Somerset county, 30 samples, 5.6
mean concentration with 33 ppb max; Bridgewater Township, 22 samples, 1.4 ppb mean concentration with 7.9 ppb
max4. In general, the average concentration of benzene in the urban atmosphere is estimated at 0.02 ppm5. In
dayofweek patterns of benzene from 6 urban sites in the Los Angeles area, California, sampled from 19892001, it
was noted that benzene was distinctly lower on Sundays and slightly lower on Saturdays and Wednesdays6.
(1) Brodzinsky R, Singh HB; Volatile Organic Chemicals In The Atmosphere: An Assessment Of Available Data 198 pp. SRI Inter 68
023452 (1982) (2) Pilar S, Graydon WF; Environ Sci Technol 7: 628712 (1973) (3) Singh WB et al; Atmos Environ 15: 60120 (1981)
(4) Bozzelli JW, Kebbekus BB; Analysis Of Selected Volatile Organic Substances In Ambient Air. Newark, NJ: NJ Inst Technol 80 pp.
(1979) (5) IARC; monograph. Some Industrial Chemicals and Dyestuffs 29: 99106 (1982) (6) Austin J; J Air Waste Manage Assoc 53:
889896 (2003)
from HSDB
URBAN/SUBURBAN: Benzene has been detected in urban air samples in London, U.K., Southampton, U.K., Budapest,
Hungary, Oslo, Norweigh, St. Petersburg, Russia, Boston, Chicago, Los Angeles, Houston, Sydney, Australia, and Tokyo,
Japan at 9,16, 27, 18, 30, 1, 1.3, 2.7, 18, 2.6, and 1.8 ppbv, respectively1. The median concentration of benzene in 39
U.S. cities from 19841985 was 12.6 ppb2. Benzene's ambient concentration was highest at nighttime and lowest by
midday due to deep convective mixing and chemical loss by OH radicals2. Since the 1960's, the ambient
atmospheric concentration of benzene has declined2. Benzene concentrations were reported for 586 ambient air
samples collected from 10 Canadian cities3. The overall mean was 4.4 ug/cu m, with Ottawa and Montreal ranging
between 5.1 and 7.6 ug/cu m3. Benzene concentrations in a traffic tunnel in London, that was poorly ventilated,
ranged from 0.0100.21 ppb4.
(1) Trost B et al; Atmos Environ 31: 39994008 (1997) (2) Singh HB, Zimmerman PB; Adv Environ Sci Technol 24: 177235 (1992) (3)
Wallace L; Environ Health Perspect 104: 11291136 (1996) (4) TsaniBazaca E et al; Environ Technol Lett 2: 30316 (1981)
from HSDB
INDOOR: In a recent benzene exposure study, day and night 12hr average concentrations of benzene were measured
for 58 residents of Valdez, Alaska1. The mean benzene concentrations in the personal, indoor, and outdoor samples
were 20, 16, and 5 ug/cu m during the summer, and 28, 25, and 11 ug/cu m during the winter, respectively1. In a
nationwide Canadian study which measured the 24hr indoor air concentrations of benzene in 754 randomly selected
homes, benzene had a mean indoor air concentration of 6.39, 5.60, 2.72, and 6.98 ug/cu m in the winter, spring,
summer, and fall seasons, respectively1. Indoor and outdoor 48hr average concentrations of benzene were
measured at 161 homes throughout much of California in which indoor samples had a mean concentration of 8.3
ug/cu m compared to 6.1 ug/cu m outdoor samples1. concentrations of benzene emitted from tobacco smoke in 5
workplaces located in Finland, 1995 ranged from 1.58 ug/cu m2. Gasoline leaking from an underground storage
tank near an elementary school in the Midwest United States location not specified created elevated levels of
benzene concentrations within the school property3. Benzene was detected in air samples collected from the
classrooms, offices/Libraries/corridors, boiler room, crawl space beneath floor, soil/duct/floor interface, and
outdoor/background at 05 ppb, 34 ppb, 4 ppb, approx 2600 ppb, 7080 ppb, and 03 ppb, respectively3. A series
of experiments were conducted in a 290 sq m singlefamily residence from June 1113, 1991 to ascertain the human
exposure to benzene from a contaminated groundwater source4. It involved an individual taking a 20 min shower
with the bathroom door closed, followed by five minutes for drying and dressing, and then opening the bathroom
door and allowing the individual to leave and have his blood, breath and urine sampled4. Whole air samples were
collected from the bathroom, shower and living room. Mean concentration of benzene coming from the shower head
for the three days was 292 ug/L4. Peak benzene levels were measured in the shower stall at 1820 mins 7581670
ug/cu m, in the bathroom at 1025 mins 366498 ug/cu m, in the bedroom at 25.530 mins 81146 ug/cu m, and
in the living room at 3670 mins 4062 ug/cu m4.
(1) Wallace L; Environ Health Perspect 104: 11291136 (1996) (2) Rothberg M et al; Ann Occup Hyg 42: 129134 (1998) (3) Moseley
CL, Meye MR; Environ Sci Technol 26: 185192 (1992) (4) Lindstrom AB et al; J Exp Anal Env Epidem 4: 183195 (1994)
from HSDB
INDOOR: Benzene geometric mean concentrations in new and established buildings in Melbourne, Australia were
reported as follows: 3.3 ug/cu m in 22 noncomplaint buildings, 61 air samples; 2.7 ug/cu m in 5 complaint buildings,
11 air samples; 1.9 outdoor samples, 27 sites, 37 samples1. Indoor benzene concentrations of 4.07 ug/cu m mean
with a max of 42 ug/cu m were reported following air analysis of 100 suburban and rural homes in New Jersey; 76
homes were above the method detection limit2.
(1) Brown SK; Indoor Air 12: 5563 (2002) (2) Weisel CP et al; Environ Sci Technol 42: 82318238 (2008)
from HSDB
RURAL/REMOTE: Benzene concentrations in 20012003 exhibited an overall reduction of 60% from previous testing in
19902003 but still above the health risk threshold1.
Statistic Whiteface Mountain
19902003
Mean 0.86
Median 0.61
Max 8.61
20012003
Mean 0.54
Median 0.47
Max 3.30
(1) Aleksic N et al; Atmos Environ 39: 78947905 (2005)
from HSDB
RURAL/REMOTE: In 100 rural air samples taken within the US from 19771980, the average concentration of benzene
was 1.4 ppb average1. Ambient air samples taken from Barrows, Alaska in 1967 contained benzene at 0.16 ppb over
a 24 hr average in 5 of 25 samples2. average benzene concentration in rural areas range from 0.117 ppb3.
Multilatitude background concentrations of benzene ppb/deg North: Atlantic Ocean 0.07/35 deg N, Pacific Ocean
0.23/45 deg N, Niwot Ridge Colorado Rockies 0.160.24 ppb4. Benzene concentrations in the Pacific Ocean ranged
from 0.05 ppb in the Northern hemisphere to 0.01 ppb in the Southern hemisphere5. Pacific Ocean, 0.581, Pullman,
WA, 0.226, Cape Meares, OR, 0.230, Norwegian Arctic, 0.0665. In 5 remote tropical sites, benzene concentrations
ranged from not detected to 1.8 ppb; average concentrations from the 5 sites ranged from 0.070.65 ppb6.
(1) Brodzinsky R, Singh HB; Volatile Organic Chemicals In The Atmosphere: An Assessment Of Available Data 198 pp. SRI Inter 68
023452 (1982) (2) Cavanagh LA et al; Environ Sci Technol 3: 2517 (1969) (3) IARC; monograph. Some Industrial Chemicals and
Dyestuffs 29: 99106 (1982) (4) Singh HB et al; Atmos Environ 19: 19119 (1985) (5) Nutmagul W, Cronn DR; J Atmos Chem 2: 415
33 (1985) (6) Greenberg JP, Zimmerman PR; Am Chem Soc Div Environ Chem 192nd Natl Mtg 26: 103 (1986)
from HSDB
RURAL/REMOTE: The estimated mean North American concentration of benzene at remote sites during 2003 was
0.142 ug/cu m1. Benzene was measured at 35 ug/cu m in the plume of a forest fire at a distance of 6 km of the seat
of the fire2. The median concentration of benzene in the Southern Appalachian Mountains was 1.1 ppb3. Benzene
concentrations range from 100200 parts per trillion over the Pacific and Atlantic Oceans due to seepage and spillage
of oil into the oceans3. Rural sampling for benzene in Canada found concentrations ranging from 0.61.2 ug/cu m4.
Benzene was detected concentration not specified in ambient air samples taken from Witaker's Forest/Sierra Nevada
Mountains, California from June 20June 22, 19905. Measurements were performed in midsummer at high ambient
temperatures and under stable meteorological conditions with high solar radiation5. Although the area was very
remote, the air samples could have been influenced by emissions from California's Central Valley and even from the
San Francisco Bay area5. The average benzene concentration for nighttime and daytime was 0.12 and 0.14 ppbv,
respectively, in air samples from Whiteface Mountain, NY taken in July 19946.
(1) McCarthy MC et al; Air Waste 56: 311 (2006) (2) Verschueren K; Handbook of Environmental Data on Organic Chemicals. 4th
ed. New York, NY: Van Nostrand Reinhold pg. 255 (2001) (3) Singh HB, Zimmerman PB; Adv Environ Sci Technol 24: 177235 (1992)
(4) Wallace L; Environ Health Perspect 104: 11291136 (1996) (5) Helmig D, Arey J; Sci Tot Env 112: 233250 (1992) (6) Khwaja H,
Narang A; Chemosphere 71: 20302043 (2008)
from HSDB
SOURCE DOMINATED: Atmospheric benzene concentrations were studied throughout the USA between 19771980 in
which out of 487 samples taken; benzene was found at an average concentration of 3.0 ppb1. The concentration of
benzene near USA chemical factories where benzene is used ranged from 0.634 ppb, near service stations 0.00033.2
ppm, and in cigarette smoke 5764 ppm2.
(1) Brodzinsky R, Singh HB; Volatile Organic Chemicals In The Atmosphere: An Assessment of Available Data 198 pp. SRI Inter 68
023452 (1982) (2) IARC; Monograph. Some Industrial Chemicals and Dyestuffs 29: 99106 (1982)
from HSDB
SOURCE DOMINATED: Benzene was emitted by precatalyst cars at 114153 mg/mile while with catalyst cars,
emissions dropped to 532 mg/mile1. Contribution of vehicle emissions from an attached garage to residential
indoor benzene levels were studied. The average benzene concentration in various samples were as follows ng/L:
coldstart background ambient 2.39; coldstart pretest 6.98; coldstart house 25.9; coldstart garage 444; hotsoak
background ambient 2.94; hotsoak pretest 3.77; hotsoak house 13.1; hotsoak garage 1212. Benzene emission
factors were 2.13 mg/km in the Gubrist highway tunnel in Zurich, Switzerland over a 2week period in 2004; emission
factors in 2002 and 1993 were 2.7 and 13.69 mg/km, respectively3. Median benzene emission from inuse
commercial aircraft during a Logan Airport operation Boston, MA in May 2003 was reported as g/kg: idle 0.3;
taxiway acceleration 0.22; approach touchdown 0.1; takeoff 0.054.
(2001) (2) Graham LA et al; J Air Waste Manage Assoc 54: 563584 (2004) (3) Legreid G et al; Environ Sci Technol 41: 70607066
(2007) (4) Herndon SC et al; Environ Sci Technol 40: 44064413 (2006)
from HSDB
SOURCE DOMINATED: In private homes, benzene levels in the air have been shown to be higher in homes with
attached garages, or where inhabitants smoke inside the house.
Thomas KW et al; J Expo Anal Environ Epidemiol 3 (1): 4973 (1993) as cited in U.S. Dept Health & Human Services/Agency for
Toxic Substances & Disease Registry; Toxicological Profile for Benzene (Update) p.180 (1997)
from HSDB
13.2.15 Food Survey Values
Benzene was found in both heat treated and canned beef at 2 ug/kg; in Jamaican rum at 120 ug/kg; in eggs ranging
from 5001900 ug/kg; and it was detected concns not specified in fruits, nuts, vegetables, dairy products, meat, fish,
poultry, eggs, and beverages1.
(1) USEPA; Ambient Water Quality Criteria: Benzene p. C5 USEPA440/580018 (1980)
from HSDB
In 1990, benzene was detected in fruit flavored mineral waters at concentrations greater than 5.0 ug/kg in Canada1.
When an investigation of benzene concentrations in beverages was performed, benzene was found at an average
concentration of 0.042, 0.67, 0.056, 0.14, 0.29, 0.12, 0.95, 0.062, 0.79, and 0.55 ug/kg in freshly squeezed fruit, retail
juice with benzoate additive, retail juice without benzoate, fruit drinks with benzoate, fruit drinks with cranberry,
without benzoate, fruit drinks excluding cranberry, without benzoate, cranberry drinks without benzoate,
carbonated soft drinks without benzoate, carbonated soft drinks with benzoate, and ice tea with benzoate,
respectively1. These data suggest the natural occurrence of benzene in fruits and fruit juices, especially from
cranberries1. Benzene is a volatile organic compound emitted by both common and pineapple guava at a
concentration of 0.10 ug/g2.
(1) Page BD et al; J AOAC Int 75: 334340 (1992) (2) Binder RG, Flath RA; J Agric Food Chem 37: 734736 (1989)
from HSDB
13.2.16 Plant Concentrations
Benzene has been detected as a plant volatile1. Benzene has been detected from 2 species of macroalgae at 20
ppb2.
(1) Graedel TC; Chemical Compounds in the Atmosphere. New York, NY: Academic Press (1978) (2) Whelan JK et al; Nature 299: 50
2 (1982)
from HSDB
Benzene occurrences in plants1.

Genus species Common name Plant
Carthamus tinctorius Safflower Flower
Elsholtzia cristata Vietnamese Balm Shoot
Levisticum officinale Lovage Root
Psidium guajava Guava Fruit
(1) USDA; Dr. Duke's Phytochemical and Ethnobotanical Databases. Plants with a chosen chemical. Benzene. Washington, DC: US
Dept Agric, Agric Res Service. Available from, as of Feb 18, 2014: http://www.arsgrin.gov/duke/
from HSDB
13.2.17 Fish/Seafood Concentrations
Benzene was detected in 5 oyster samples from the Inner Harbor Navigational Canal in Lake Pontchartrain, LA at 220
ppb wet weight1. Composite clam samples from Chef Menteur Pass in Lake Pontchartain, LA contained benzene at
260 ppb wet weight; however clam samples from The Rigolets did not contain benzene1. Abstract: PubMed
(1) Ferrario JB et al; Bull Environ Contam Toxicol 34: 24655 (1985)
from HSDB
13.2.18 Milk Concentrations
Benzene was detected in all 8 samples of mothers milk from women in 4 US urban areas1.
(1) Pellizzari ED et al; Environ Sci Technol 16: 7815 (1982)
from HSDB
13.2.19 Other Environmental Concentrations
Benzene has been detected in cigarette smoke14. Median benzene concentrations of 2.3 ug/cu m 0.4 minimum,
11.9 maximum, 3.7 ug/cu m mean were measured in 41 air samples from smoking premises consisting of 37 cafes
and 19 restaurants in Girona, Spain. Mean concentrations of 0.7 and 0.9 were measured in samples from nonsmoking
premises and outdoors, respectively, from the same region2. The delivery of benzene in mainstream cigarette smoke
ranges from 3.7 to 56.8 mg/cigarette3. A range of 4764 ppm in tobacco smoke has also been reported5.
(1) Rodgman A, Perfetti TA; The Chemical Components of Tobacco and Tobacco Smoke. Boca Raton, FL: CRC Press p. 47 (2009) (2)
Alonso M et al; Environ Sci Technol 44: 82898294 (2010) (3) Polzin GM et al; Environ Sci Technol 41: 12971302 (2007) (4) Talhout
R et al; Int J Environ Res Public Health 8: 613628 (2011) (5) Clayton GD, Clayton FE; Patty's Industrial Hygiene And Toxicology, 4th
ed., New York, NY: John Wiley & Sons, Vol IIB p. 1302 (1994)
from HSDB
Benzene exposurerelevant emission factors ug/cigarette at three furnishing levels and three ventilation rates in a 50
m sq room1.
Furnishing 2/hr 0.6/hr 0.3/hr
wallboard only 517 438 387
wallboard/carpet 457 432 400
fully furnished 429 435 429
(1) Singer BC et al; Environ Sci Technol 36: 84653 (2002)
from HSDB
13.2.20 Probable Routes of Human Exposure
According to the 2006 TSCA Inventory Update Reporting data, the number of persons reasonably likely to be exposed
in the industrial manufacturing, processing, and use of benzene is 1000 or greater; the data may be greatly
underestimated1.
(1) US EPA; Inventory Update Reporting (IUR). Nonconfidential 2006 IUR Records by Chemical, including Manufacturing, Processing
and Use Information. Washington, DC: U.S. Environmental Protection Agency. Available from, as of Feb 18, 2014:
http://cfpub.epa.gov/iursearch/index.cfm
from HSDB
NIOSH NOES Survey 19811983 has statistically estimated that 272,275 workers 143,066 of these were female were
potentially exposed to benzene in the US1. Occupational exposure to benzene may occur through inhalation and
dermal contact with this compound at workplaces where benzene is produced or used. Monitoring data indicate that
the general population may be exposed to benzene via inhalation of ambient air, ingestion of food and drinking
water, and dermal contact with consumer products containing benzeneSRC.
(1) NIOSH; NOES. National Occupational Exposure Survey conducted from 19811983. Estimated numbers of employees potentially
exposed to specific agents by 2digit standard industrial classification (SIC). Available from, as of Feb 18, 2014:
http://www.cdc.gov/noes/
from HSDB
The National Occupational Health Survey conducted from 1972 to 1974 estimated that 147,600 U.S. workers
potentially were exposed to benzene NIOSH 1976.
DHHS/National Toxicology Program; Twelfth Report on Carcinogens: Benzene (71432) (2011). Available from, as of February 21,
2014: http://ntp.niehs.nih.gov/ntp/roc/twelfth/profiles/Benzene.pdf
from HSDB
Analysis and modeling of 20,000 airborne breathing zone air samples of Deepwater Horizon oil spill offshore cleanup
workers were taken during the six months following the incident. Results indicate that measurements were primarily
due to ship engine exhaust. Estimated contributions to airborne benzene concentration were 34% oil thickness, 23%
wind speed, 21% fraction BTEX dissolved in water, and 22% BTEX content in oil1.
Before cap After cap
Number samples 3089 1856
% Detection 98 99
Mean ppm 0.0056 0.013
99th percentile ppm 0.031 0.025
95th percentile ppm 0.016 0.012
average detection limit ppm 0.014 0.014
(1) Avens HJ et al; Environ Sci Technol 45(17): 73727379 (2011)
from HSDB
Benzene concentrations at four Hong Kong restaurants employing different cooking styles1.
Indoor benzene Outdoor benzene
Types Stove fuel Way of cooking
concn concn
Liquified Frying in oil on hot pan in dining

Korean BBQ 16.919.8 9.312.6
petroleum gas area
Chinese hot Liquified

Boiling in soup in dining area 7.412.2 3.33.8
pot petroleum gas
Chinese dim Steaming in fixed food court in

Natural gas 8.710 8.38.7
sum dining area
Western
Natural gas Prepared in kitchen 3.74.3 6.57.2
cafeteria
(1) Lee SC et al; Sci Total Environ 279: 18193 (2001)
from HSDB
Human populations are primarily exposed to benzene through inhalation of contaminated ambient air particularly in
areas with heavy traffic and around filling stations. In addition, air close to manufacturing plants which produce or use
benzene may contain high concentrations of benzene1,2. Another source of exposure is from inhalation of tobacco
smoke1.
(1) IARC; Monograph, Some Industrial Chem and Dyestuffs 29: 99106 (1982) (2) Graedel TE; Chem Compounds in the Atmos, New
York, NY Academic Press (1978)
from HSDB
Rough estimates of average ambient groundlevel benzene concentrations over an 8 hour period were calculated
based on an emission rate of 100 g/sec from a manufacturing plant. Benzene concentrations in pg/cu m are
estimated to be 11,000 at 0.15 km, 6,100 at 0.3 km, 3,800 at 0.45 km, 2,800 at 0.6 km, 2,100 at 0.75 km, 740 at 1.6 km,
370 at 2.5 km, 220 at 4.0 km, 120 at 6.0 km, 62 at 9.0 km, 34 at 14.0 km, and 20 at 20.0 km distance from the
manufacturing plant1.
(1) Mara SJ, Shonh SL; Assesment of Human Exposures to Atmospheric Benzene. Menlo Park, CA: SRI. USEPA450/378031. NTIS PB
284 203 (1978)
from HSDB
Benzene was detected in 3 out of 70 samples taken from 46 spray painting workshops in Sydney, Australia at a
concentration of 1 mg/cu m in 19891. Worker exposure in aircraft paint stripping and spraying industries ranged on
average from 0.14 0.77 ppm for primer and 0.150.94 surface paint over 12 hour sampling periods2. In a study of
inauto and inbus exposures to volatile organic compounds for commutes on an urbansuburban route in Korea
from November 21 to December 22, 1994, revealed that mean inauto concentrations of benzene were 30.6 ug/cu m
along urban routes and 18.3 ug/cu m along suburban routes while mean inbus concentrations were 20.2 ug/cu m
along urban routes and 11.7 ug/cu m along suburban routes3. In a 200trip study of invehicle air of Los Angeles
commuters, an average concentration of benzene at 40 ug/cu m during rush hour was detected4. Mean benzene
exposures of 2.55, 5.97 and 4.70 in home out door, home indoor and personal air samples in winter, 1999 1.31, 1.75
and 3.09 in home out door, home indoor and personal air samples in summer, 1999 were assessed for 46 high school
students in the West Central Harlem section of NYC5.
(1) Winder C et al; Ann Occup Hyg 36: 38594 (1992) (2) Uang S et al; Sci Total Environ 356: 3844 (2006) (3) Jo WK et al; Air Waste
Manage Assoc 46: 749754 (1996) (4) Wallace L; Environ Health Perspect 104: 11291136 (1996) (5) Kinney PL et al; Environ Health
Perspect 110: 539546 (2002)
from HSDB
13.2.21 Average Daily Intake
Two studies of benzene levels in foods have confirmed the conclusion that ingesting food and beverages are an
unimportant pathway for benzene exposure. In a study of more than 50 foods, most contained benzene below 2 ng/g
ppbw. A Canadian review of benzene exposures concluded that food and drinking water each contributed only about
0.02 ug/kg benzene per day compared to a total intake of 2.4 ug/kg per day from airborne exposures 3.3 ug/kg/day
if exposed to cigarette smoke. In a 1980's study of nonoccupational benzene exposure, it was found that more than
99% of the total personal exposure was through air and that a global average personal exposure for benzene was
about 15 ug/cu m. Roughly half the total benzene exposure in the United States was borne by smokers. For non
smokers, most benzene exposure ultimately was derived from auto exhaust or gasoline vapor emissions. A series of
experiments were conducted in a 290 sq m singlefamily residence from June 1113, 1991 to ascertain the human
exposure to benzene from a contaminated groundwater source. It involved an individual taking a 20 min shower with
the bathroom door closed, followed by five minutes for drying and dressing, and then opening the bathroom door
and allowing the individual to leave and have his blood, breath and urine sampled. Whole air samples were collected
from the bathroom, shower and living room. The inhalation exposure to benzene of an individual in the living room
averaged 72 ug for the three days. The individual taking the shower had an average inhalation dose of 113 ug and an
average dermal dose of 168 ug exposure = 40% inhalation, 60% dermal. There may be a large number of cases
where well water is contaminated by benzene at low concentrations. A number of studies have reported finding
benzene at levels on the order of 5 ng/L in surface and well waters. However, these levels correspond to a daily intake
of <10 ng benzene, assuming 2 liters of water drunk daily. This amount is only 0.5% of the average daily intake for
nonsmokers of 200 ng from air. Thus, it is concluded that the effect of contaminated water on total benzene intake is
negligible1.[1 Wallace L; Environ Health Perspect 104: 11291136 1996] Full text: PMC1469757 Abstract: PubMed
from HSDB
13.2.22 Body Burdens
Benzene was detected in all 8 samples of mothers' milk from women living in 4 USA urban areas1. Breath samples
from persons without specific exposure to benzene ranged from 8 to 20 ppb2. Whole blood samples from 250
subjects 121 males, 129 females ranged from not detected to 5.9 ppb, mean 0.8 ppb3. In FY82, the National
Human Adipose Tissue Survey specimens found that of 46 composite samples, 96% tested positive to benzene
concentrations were >4 ppb for wet tissue with a max concentration of 97 ppb max4.
(1) Pellizzari ED et al; Environ Sci Technol 16: 7815 (1982) (2) IARC; Monograph. Some Industrial Chemicals and Dyestuffs. 29: 99
106 (1982) (3) Antoine SR et al; Bull Environ Contam Toxicol 36: 36471 (1986) (4) Stanley JS; Broad Scan Analysis of the FY82
National Human Adipose Tissue Survey Specimens Vol. I Executive Summary p. 5 USEPA560/586035 (1986)
from HSDB
In a 1980's study of nonoccupational benzene exposure, it was found that smokers had an average benzene body
burden about 6 to 10 times that of nonsmokers, and received about 90% of their benzene exposure from smoking1.
The mean benzene concentration found in the breath and blood of 1,683 individuals was 13.1 and 131 ng/L,
respectively1.[1 Wallace L; Environ Health Perspect 104: 11291136 1996] Full text: PMC1469757 Abstract:
PubMed
from HSDB
14 Literature
14.1 Depositor Provided PubMed Citations
CLICK TO LOAD...
from PubChem
14.2 NLM Curated PubMed Citations
CLICK TO LOAD...
from PubChem
14.3 Synthesis References

Copisarow, Maurice; Long, Cyril N H. The FriedelCrafts' reaction. II. Migration of halogen atoms in the benzene
nucleus. Journal of the Chemical Society, Transactions 1921, 119 4427.
14.4 Metabolite References
Download
PMID Reference
Wiwanitkit V, Soogarun S, Suwansaksri J: Urine phenol and myeloperoxidase index: an observation in

15370219
benzene exposed subjects. Leuk Lymphoma. 2004 Aug;458:16435.
Wang S, Chen H, Wang X: [Studies on relationship between exposure to low concentration of mixed
11372393 benzene and lower quality of semen and very early fetal loss]. Zhonghua Yu Fang Yi Xue Za Zhi. 2000
Sep;345:2713.
PMID Reference
Zhang L, Wang Y, Shang N, Smith MT: Benzene metabolites induce the loss and long arm deletion of
9593466
chromosomes 5 and 7 in human lymphocytes. Leuk Res. 1998 Feb;222:10513.
Fabiani R, De Bartolomeo A, Morozzi G: Involvement of oxygen free radicals in the serummediated

15920754
increase of benzoquinone genotoxicity. Environ Mol Mutagen. 2005 Oct;463:15663.
Turteltaub KW, Mani C: Benzene metabolism in rodents at doses relevant to human exposure from
12675491
urban air. Res Rep Health Eff Inst. 2003 Feb;113:126; discussion 2735.
15 Patents
15.1 DepositorSupplied Patent Identifiers
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from PubChem
16 Biomolecular Interactions and Pathways
16.1 Protein Bound 3D Structures
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from PubChem
16.2 Biosystems and Pathways
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from PubChem
17 Biological Test Results
17.1 BioAssay Results
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from PubChem
18 Classification
18.1 Ontologies
18.1.1 MeSH Tree
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from MeSH
18.1.2 ChEBI Ontology
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from ChEBI
18.1.3 KEGG: Carcinogen
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from KEGG
18.1.4 WIPO IPC
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from WIPO
19 Information Sources
1. CAMEO Chemicals /source/CAMEO Chemicals
Benzene
https://cameochemicals.noaa.gov/chemical/2577 https://cameochemicals.noaa.gov/chemical/2577
2. ChemIDplus /source/ChemIDplus
Benzene
https://chem.nlm.nih.gov/chemidplus/sid/0000071432 https://chem.nlm.nih.gov/chemidplus/sid/0000071432
Petroleum ether
Benzene, labeled with carbon14 and tritium
3. EPA Chemicals under the TSCA /source/EPA Chemicals under the TSCA
Benzene
http://www.epa.gov/chemicaldatareporting http://www.epa.gov/chemicaldatareporting
4. EPA DSStox /source/EPA DSStox

Benzene
https://comptox.epa.gov/dashboard/dsstoxdb/results?search=DTXSID3039242
https://comptox.epa.gov/dashboard/dsstoxdb/results?search=DTXSID3039242
5. European Chemicals Agency ECHA /source/European Chemicals Agency ECHA

Naphtha
https://echa.europa.eu/ https://echa.europa.eu/
Naphtha
https://echa.europa.eu/informationonchemicals/clinventorydatabase//discli/details/103807
benzene
6. Human Metabolome Database /source/Human Metabolome Database

Benzene
http://www.hmdb.ca/metabolites/HMDB01505 http://www.hmdb.ca/metabolites/HMDB01505
7. ILOICSC /source/ILOICSC
BENZENE
http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=0015 http://www.ilo.org/dyn/icsc/showcard.display?p_card_id=0015
8. OSHA Occupational Chemical DB /source/OSHA Occupational Chemical DB

BENZENE
http://www.osha.gov/chemicaldata/chemResult.html?RecNo=491 http://www.osha.gov/chemicaldata/chemResult.html?
RecNo=491
NAPHTHA (COAL TAR)
http://www.osha.gov/chemicaldata/chemResult.html?RecNo=706 http://www.osha.gov/chemicaldata/chemResult.html?
RecNo=706
9. The National Institute for Occupational Safety and Health NIOSH /source/The National
Institute for Occupational Safety and Health NIOSH
Benzene
https://www.cdc.gov/nioshrtecs/CY155CC0.html https://www.cdc.gov/nioshrtecs/CY155CC0.html
Benzene
https://www.cdc.gov/niosh/npg/npgd0049.html https://www.cdc.gov/niosh/npg/npgd0049.html
Benzin
https://www.cdc.gov/nioshrtecs/DE2E3BF0.html https://www.cdc.gov/nioshrtecs/DE2E3BF0.html
10. DOT Emergency Response Guidebook /source/DOT Emergency Response Guidebook
benzene
http://phmsa.dot.gov/hazmat/outreachtraining/erg http://phmsa.dot.gov/hazmat/outreachtraining/erg
11. NJDOH RTK Hazardous Substance List /source/NJDOH RTK Hazardous Substance List
benzene
http://nj.gov/health/eoh/rtkweb/documents/fs/0197.pdf http://nj.gov/health/eoh/rtkweb/documents/fs/0197.pdf
12. CDCATSDR Toxic Substances Portal /source/CDCATSDR Toxic Substances Portal

https://www.atsdr.cdc.gov/substances/toxsubstance.asp?toxid=14 https://www.atsdr.cdc.gov/substances/toxsubstance.asp?
toxid=14
13. EPA Air Toxics /source/EPA Air Toxics

Benzene
http://www3.epa.gov/ttn/atw/hlthef/benzene.html http://www3.epa.gov/ttn/atw/hlthef/benzene.html
14. NCIt /source/NCIt

Benzene
https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C302
https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C302
15. HSDB /source/HSDB

BENZENE
http://toxnet.nlm.nih.gov/cgibin/sis/search/r?dbs+hsdb:@term+@rn+@rel+71432 http://toxnet.nlm.nih.gov/cgi
bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+71432
16. OSHA Chemical Sampling Information /source/OSHA Chemical Sampling Information

Naphtha (Coal Tar)
https://www.osha.gov/dts/chemicalsampling/data/CH_255700.html
Benzene
17. FAO/WHO Food Additive Evaluations JECFA /source/FAO/WHO Food Additive Evaluations
JECFA
BENZENE
http://apps.who.int/foodadditivescontaminantsjecfadatabase/chemical.aspx?chemID=170 http://apps.who.int/foodadditives
contaminantsjecfadatabase/chemical.aspx?chemID=170
18. USGS Columbia Environmental Research Center /source/USGS Columbia Environmental

Research Center
BENZENE
https://www.cerc.usgs.gov/data/acute/qrychemdesc.asp?Chemical=B0090
https://www.cerc.usgs.gov/data/acute/qrychemdesc.asp?Chemical=B0090
19. EU REGULATION EC No 1272/2008 /source/EU REGULATION EC No 1272/2008

benzene
http://ec.europa.eu/growth/sectors/chemicals/classificationlabelling/index_en.htm
http://ec.europa.eu/growth/sectors/chemicals/classificationlabelling/index_en.htm
20. NITECMC /source/NITECMC

Benzene
http://www.safe.nite.go.jp/english/ghs/14mhlw2197e.html http://www.safe.nite.go.jp/english/ghs/14mhlw2197e.html
21. Safe Work Australia HCIS /source/Safe Work Australia HCIS

71432
http://hcis.safeworkaustralia.gov.au/ http://hcis.safeworkaustralia.gov.au/
22. FDA/SPL Indexing Data /source/FDA/SPL Indexing Data

J64922108F
https://www.fda.gov/ForIndustry/DataStandards/SubstanceRegistrationSystemUniqueIngredientIdentifierUNII/
https://www.fda.gov/ForIndustry/DataStandards/SubstanceRegistrationSystemUniqueIngredientIdentifierUNII/
23. NIOSH Manual of Analytical Methods /source/NIOSH Manual of Analytical Methods

71432
http://www.cdc.gov/niosh/docs/2003154/pdfs/2549.pdf http://www.cdc.gov/niosh/docs/2003154/pdfs/2549.pdf
8030306
71432
71432
71432
24. NIST /source/NIST

Benzene
http://www.nist.gov/srd/nist1a.cfm http://www.nist.gov/srd/nist1a.cfm
25. The Cambridge Structural Database /source/The Cambridge Structural Database

The Cambridge Structural Database provides access to 3D structures of molecules determined experimentally using diffraction
techniques.
http://www.ccdc.cam.ac.uk/pages/Home.aspx http://www.ccdc.cam.ac.uk/pages/Home.aspx
26. Wikipedia /source/Wikipedia

benzene
https://en.wikipedia.org/wiki/Benzene https://en.wikipedia.org/wiki/Benzene
cyclohexatriene
https://www.wikidata.org/wiki/Q26841227 https://www.wikidata.org/wiki/Q26841227
27. PubChem
Data deposited in or computed by PubChem
https://pubchem.ncbi.nlm.nih.gov https://pubchem.ncbi.nlm.nih.gov
28. MeSH /source/MeSH

Benzene
https://www.ncbi.nlm.nih.gov/mesh/68001554 https://www.ncbi.nlm.nih.gov/mesh/68001554
MeSH Tree
http://www.nlm.nih.gov/mesh/meshhome.html http://www.nlm.nih.gov/mesh/meshhome.html
29. ChEBI /source/ChEBI

ChEBI Ontology
http://www.ebi.ac.uk/chebi/userManualForward.do#ChEBI%20Ontology
http://www.ebi.ac.uk/chebi/userManualForward.do#ChEBI%20Ontology
30. KEGG /source/KEGG

Carcinogen
http://www.genome.jp/dbgetbin/www_bget?brite:br08008 http://www.genome.jp/dbgetbin/www_bget?brite:br08008
31. WIPO /source/WIPO

International Patent Classification
http://www.wipo.int/classifications/ipc/ http://www.wipo.int/classifications/ipc/
32. NCBI
LinkOut is a service that allows one to link directly from NCBI databases to a wide range of information and services beyond
NCBI systems.
https://www.ncbi.nlm.nih.gov/projects/linkout https://www.ncbi.nlm.nih.gov/projects/linkout

Benzene - C6H6 - PubChem

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2017610 benzene|C6H6PubChem

Compound Summary for CID 241

Benzene Cite this Record

PubChem CID: 241

Chemical Names: Benzene; Benzol; Benzole; Cyclohexatriene; Pyrobenzole; Benzine More...

Molecular Formula: C6H6

Drug Information: Therapeutic Uses FDA UNII

Safety Summary: Laboratory Chemical Safety Summary LCSS

PUBCHEM COMPOUND BENZENE Create Date: 20040916

3 Names and Identifiers

4 Chemical and Physical Properties

7 Drug and Medication Information

8 Food Additives and Ingredients

9 Pharmacology and Biochemistry

10 Use and Manufacturing

12 Safety and Hazards

16 Biomolecular Interactions and Pathways

17 Biological Test Results

Show Hydrogens Show Atoms Animate

3 Names and Identifiers

3.1 Computed Descriptors

3.1.1 IUPAC Name

3.1.3 InChI Key

3.1.4 Canonical SMILES

3.2 Molecular Formula

3.3 Other Identifiers

3.3.3 ICSC Number

3.3.4 RTECS Number

Description chemical compound

3.4.1 MeSH Synonyms

3.4.2 DepositorSupplied Synonyms

4 Chemical and Physical Properties

4.1 Computed Properties

Property Name Property Value

Molecular Weight 78.114 g/mol

Hydrogen Bond Donor Count 0

Hydrogen Bond Acceptor Count 0

Rotatable Bond Count 0

Topological Polar Surface Area 0 A^2

Monoisotopic Mass 78.047 g/mol

Exact Mass 78.047 g/mol

Compound Is Canonicalized true

Heavy Atom Count 6

Defined Atom Stereocenter Count 0

Undefined Atom Stereocenter Count 0

Defined Bond Stereocenter Count 0

Undefined Bond Stereocenter Count 0

Isotope Atom Count 0

CovalentlyBonded Unit Count 1

4.2 Experimental Properties

4.2.1 Physical Description

COLOURLESS LIQUID WITH CHARACTERISTIC ODOUR.

Colorless to lightyellow liquid with an aromatic odor.

Reddishbrown, mobile liquid with an aromatic odor.

Clear, colorless liquid

Orthorhombic prisms or liquid

Colorless to lightyellow liquid [Note: A solid below 42 degrees F]

Taste threshold in water is 0.54.5 mg/l.