The Registry of Toxic Effects of Chemical Substances

Benzene

RTECS #: CY1400000

CAS #: 71-43-2

UPDATE: May 2005 MW: 78.12 MF: C6H6


NOTE:

TABLE OF CONTENTS:
  1. SYNONYMS:
  2. SKIN AND EYE IRRITATION DATA:
  3. MUTATION DATA:
  4. REPRODUCTIVE EFFECTS DATA:
  5. TUMORIGENIC DATA:
  6. ACUTE TOXICITY DATA:
  7. OTHER MULTIPLE DOSE DATA:
  8. REVIEWS:
  9. STANDARDS AND REGULATIONS:
  10. NIOSH DOCUMENTATION AND SURVEILLANCE:
  11. STATUS IN FEDERAL AGENCIES:
  12. REFERENCES:

SYNONYMS:

  1. (6) Annulene
  2. Benzeen (Dutch)
  3. Benzen (Polish)
  4. Benzene (ACGIH:OSHA)
  5. Carbon oil
  6. Cyclohexatriene
  7. NCI - C55276
  8. RCRA waste number U019
  9. Benzin (Obs.)
  10. Benzine (Obs.)
  11. Benzol (OSHA)
  1. Benzole
  2. Benzolene
  3. Benzolo (Italian)
  4. Bicarburet of hydrogen
  5. Coal naphtha
  6. Fenzen (Czech)
  7. Mineral naphtha
  8. Phene
  9. Phenyl hydride
  10. Pyrobenzol
  11. Pyrobenzole


SKIN AND EYE IRRITATION DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
eye
rabbit 		88 mg moderate AMIHAB 14,387,1956
eye
rabbit 		2 mg/24 hour severe 85JCAE -,25,1986
skin
rabbit 		15 mg/24 hour open irritation test mild AIHAAP 23,95,1962
skin
rabbit 		20 mg/24 hour moderate 85JCAE -,25,1986


MUTATION DATA AND REFERENCES:

SYSTEM TEST ROUTE/
ORGANISM/
TISSUE 		DOSE REFERENCE
cytogenetic analysis hamster lung 550 mg/L PMRSDJ 5,427,1985
cytogenetic analysis hamster ovary 600 mg/L PMRSDJ 5,443,1985
cytogenetic analysis inhalation
human 		125 ppm/1 year AEHLAU 22,373,1971
cytogenetic analysis human leukocyte 1 mmol/L/72 hour MUREAV 47,75,1978
cytogenetic analysis human lymphocyte 1 mg/L BZARAZ 26(12),38,1973
cytogenetic analysis unreported route
human 		10 ppm/4 week ENVRAL 19,33,1979
cytogenetic analysis oral
mouse 		20 mg/kg BEXBAN 96,1741,1984
cytogenetic analysis intraperitoneal
mouse 		264 mg/kg/3 day- continuous ENMUDM 2,43,1980
cytogenetic analysis inhalation
mouse 		3,000 ppm EVSRBT 25,257,1982
cytogenetic analysis skin
mouse 		8.5 gm/kg EMMUEG 37,185,2001
cytogenetic analysis oral
mouse 		0.5 ppb EMMUEG 39,69,2002
cytogenetic analysis inhalation
rat 		300 mg/m3/16 week- intermittent GISAAA 42(1),32,1977
cytogenetic analysis subcutaneous
rat 		2,400 mg/kg/12 day- intermittent GISAAA 37(10),36,1972
cytogenetic analysis intraperitoneal
rat 		234 mg/kg MUREAV 242,111,1990
cytogenetic analysis oral
rat 		39,060 µg/kg MUREAV 298,81,1992
cytogenetic analysis subcutaneous
rat 		7.5 mL/kg/12 week- intermittent TCMUD8 20,329,2000
cytogenetic analysis oral
rat 		0.5 ppb EMMUEG 39,69,2002
cytogenetic analysis subcutaneous
rabbit 		8,400 mg/kg PSDTAP 15,275,1974
dominant lethal test oral
mouse 		1 mg/kg ARTODN 39,173,1978
dominant lethal test intraperitoneal
mouse 		5 mg/kg TPKVAL 15,30,1979
DNA adduct intraperitoneal
mouse 		2,640 mg/kg/3 day- continuous CRNGDP 17,151,1996
DNA adduct intraperitoneal
mouse 		5,000 mg/kg/5 day- intermittent MUREAV 566,99,2004
DNA adduct intraperitoneal
mouse 		0.5 mg/kg/1 day MUREAV 566,99,2004
DNA adduct intraperitoneal
rat 		0.5 mg/kg/1 day MUREAV 566,99,2004
DNA damage hamster ovary 17 mmol/L PMRSDJ 5,367,1985
DNA damage mouse lymphocyte 3,840 µmol/L MUREAV 203,155,1988
DNA damage intraperitoneal
mouse 		2,000 mg/kg MUREAV 493,39,2001
DNA damage oral
mouse 		2,000 mg/kg MUREAV 493,39,2001
DNA damage subcutaneous
rabbit 		2,344 mg/kg ARTODN 63,209,1989
DNA inhibition human leukocyte 2,200 µmol/L INHEAO 12,23,1974
DNA inhibition human HeLa cell 2,200 µmol/L INHEAO 12,23,1974
DNA inhibition oral
mouse 		20 gm/kg ARGEAR 51,605,1981
DNA inhibition intraperitoneal
mouse 		880 mg/kg RCOCB8 60,27,1988
DNA inhibition inhalation
mouse 		3,000 ppm/4 hour- continuous RCOCB8 60,27,1988
DNA inhibition mouse bone marrow 3 mmol/L RCOCB8 60,27,1988
DNA inhibition inhalation
rat 		400 ppm BLUTA9 21,250,1970
DNA inhibition subcutaneous
rabbit 		2 gm/kg ACHAAH 38,104,1967
unscheduled DNA synthesis rat liver 1 mmol/L PMRSDJ 5,371,1985
mutation in microorganisms mouse lymphocyte 62,500 µg/L (+enzymatic activation step) PMRSDJ 5,587,1985
mutation in microorganisms mouse embryo 2,500 mg/L (+enzymatic activation step) PMRSDJ 5,639,1985
mutation in microorganisms Salmonella typhimurium 10 ppm (-enzymatic activation step) EVHPAZ 82,81,1989
mutation in microorganisms Saccharomyes cerevisiae 549 mg/L (+enzymatic activation step) PMRSDJ 5,271,1985
micronucleus test mouse embryo 12,500 nmol/L EMMUEG 19(Suppl 20),21,1992
micronucleus test subcutaneous
mouse 		440 mg/kg CBINA8 39,129,1982
micronucleus test oral
mouse 		40 mg/kg MUREAV 147,294,1985
micronucleus test intraperitoneal
mouse 		264 mg/kg/24 hour MUTAEX 2,111,1987
micronucleus test inhalation
mouse 		10 ppm/6 hour ENMUDM 8,29,1986
micronucleus test inhalation
mouse 		15,000 ppm/5 week MUTAEX 16,163,2001
micronucleus test inhalation
mouse 		100 ppm/6 hour/2 week- intermittent TOXID9 72(Supp 1),228,2003
micronucleus test inhalation
mouse 		100 ppm/2 week- intermittent TOSCF2 72,201,2003
micronucleus test multiple
non-mammalian species 		10 mg/L/36 hour MUREAV 534,93,2003
micronucleus test multiple
non-mammalian species 		10 mg/L/90 minute MUREAV 534,93,2003
micronucleus test inhalation
rat 		1 ppm/6 hour ENMUDM 8,29,1986
micronucleus test intraperitoneal
rat 		0.3 mL/kg TCMUD8 21,181,2001
micronucleus test intratracheal
rat 		0.3 mL/kg TCMUD8 21,181,2001
gene conversion and mitotic recombination Saccharomyes cerevisiae 275 mg/L PMRSDJ 5,271,1985
mutation in mammalian somatic cells hamster embryo 10 µmol/L MUREAV 373,113,1997
mutation in mammalian somatic cells human lymphocyte 1 gm/L PMRSDJ 5,497,1985
mutation in mammalian somatic cells mouse lymphocyte 12,500 µg/L PMRSDJ 5,525,1985
mutation in mammalian somatic cells inhalation
mouse 		40 ppb/6 week- continuous MUREAV 268,49,1992
mutation in mammalian somatic cells oral
mouse 		2 gm/kg/5 day- continuous EMMUEG 28,342,1996
morphological transform hamster embryo 100 µg/L CRNGDP 4,291,1983
morphological transform mouse embryo 1 gm/L PMRSDJ 5,659,1985
morphological transform mouse fibroblast 150 gm/L CRNGDP 3,1235,1982
morphological transform mouse fibroblast 0.1 mg/L/21 day (-enzymatic activation step) EMMUEG 35,300,2000
other mutation test systems cat bone marrow 1 mmol/L CBINA8 42,353,1982
other mutation test systems inhalation
grasshopper 		14 pph/16 hour MUREAV 113,467,1983
other mutation test systems human lymphocyte 5 µmol/L CNREA8 45,2471,1985
other mutation test systems oral
mouse 		2 gm/kg MUREAV 343,157,1995
other mutation test systems mouse other cell types 5 mmol/L CBTOE2 2,231,1986
other mutation test systems mouse lymphocyte 10 mmol/L TOLED5 29,161,1985
other mutation test systems intraperitoneal
non-mammalian species 		75 gm/kg ACHAAH 26,281,1961
other mutation test systems rat liver 1 mmol/L CBINA8 42,353,1982
other mutation test systems rat bone marrow 1 mmol/L CBINA8 42,353,1982
other mutation test systems subcutaneous
rat 		1 gm/L NJMSAG 28,204,1966
other mutation test systems subcutaneous
rat 		2,200 mg/kg CBINA8 42,353,1982
other mutation test systems rabbit bone marrow 1 mmol/L CBINA8 42,353,1982
sister chromatid exchange hamster ovary 750 mg/L SCIEAS 236,933,1987
sister chromatid exchange human lymphocyte 200 µmol/L CNREA8 43,1330,1983
sister chromatid exchange inhalation
mouse 		10 ppm/6 hour ENMUDM 8,29,1986
sister chromatid exchange intraperitoneal
mouse 		5 gm/kg ENMUDM 5,450,1983
sister chromatid exchange inhalation
rat 		3 ppm/6 hour ENMUDM 8,29,1986
sister chromatid exchange rat leukocyte 1 mmol/L MUREAV 300,241,1993
sex chromosome loss and nondisjunction Aspergillus nidulans 35,000 ppm MUREAV 147,288,1985
sex chromosome loss and nondisjunction oral
Drosophila melanogaster 		7,500 ppm CONAEL 1,35,1985
sex chromosome loss and nondisjunction multiple
Drosophila melanogaster 		27,000 ppm EMMUEG 25,211,1995
sex chromosome loss and nondisjunction hamster liver 62,500 µg/L PMRSDJ 5,397,1985
sex chromosome loss and nondisjunction hamster embryo 30 µmol/L MUREAV 373,113,1997
specific locus test oral
Drosophila melanogaster 		11,250 µmol/L PMRSDJ 5,325,1985
specific locus test oral
mouse 		0.5 ppb EMMUEG 39,69,2002
specific locus test oral
rat 		0.5 ppb EMMUEG 39,69,2002


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
mouse 		lowest published toxic concentration: 500 ppm/7 hour (6-15 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Musculoskeletal system 		AIHAAP 40,993,1979
inhalation
mouse 		lowest published toxic concentration: 500 mg/m3/12 hour (6-15 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Musculoskeletal system 		ATSUDG 8,425,1985
inhalation
mouse 		lowest published toxic concentration: 5 ppm (6-15 day pregnant) Reproductive: Effects on embryo or fetus: Cytological changes (including somatic cell genetic material)

Reproductive: Specific developmental abnormalities: Blood and lymphatic systems (including spleen and marrow) 		TXCYAC 42,171,1986
inhalation
mouse 		lowest published toxic concentration: 20 ppm/6 hour (6-15 day pregnant) Reproductive: Specific developmental abnormalities: Blood and lymphatic systems (including spleen and marrow) FAATDF 10,224,1988
inhalation
rat 		lowest published toxic concentration: 670 mg/m3/24 hour (15 day prior to copulation/1-22 day pregnant) Reproductive: Effects on fertility: Female fertility index (e.g., # females pregnant per # sperm positive females; # females pregnant per # females mated) HYSAAV 33(1-3),327,1968
inhalation
rat 		lowest published toxic concentration: 56,600 µg/m3/24 hour (1-22 day pregnant) Reproductive: Effects on newborn: Biochemical and metabolic HYSAAV 33(7-9),112,1968
inhalation
rat 		lowest published toxic concentration: 50 ppm/24 hour (7-14 day pregnant) Reproductive: Effects on embryo or fetus: Extra embryonic structures (e.g., placenta, umbilical cord)

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) 		JHEMA2 24,363,1980
inhalation
rat 		lowest published toxic concentration: 150 ppm/24 hour (7-14 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Specific developmental abnormalities: Musculoskeletal system 		JHEMA2 24,363,1980
inhalation
rabbit 		lowest published toxic concentration: 1 gm/m3/24 hour (7-20 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on fertility: Abortion

Reproductive: Effects on embryo or fetus: Fetal death 		ATSUDG 8,425,1985
inhalation
rabbit 		lowest published toxic concentration: 1 gm/m3/24 hour (7-20 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Other developmental abnormalities 		ATSUDG 8,425,1985
inhalation
rabbit 		lowest published toxic concentration: 500 ppm/7 hour (6-18 day pregnant) Reproductive: Other effects on female NTIS** OTS0545179
intraperitoneal
mouse 		lowest published toxic dose: 5 mg/kg (1 day male) Reproductive: Effects on fertility: Pre- implantation mortality (e.g., reduction in number of implants per female; total number of implants per corpora lutea)

Reproductive: Effects on embryo or fetus: Fetal death 		TPKVAL 15,30,1979
intraperitoneal
mouse 		lowest published toxic dose: 219 mg/kg (14 day pregnant) Reproductive: Specific developmental abnormalities: Blood and lymphatic systems (including spleen and marrow)

Reproductive: Specific developmental abnormalities: Hepatobiliary system 		EMMUEG 18,1,1991
intravenous
mouse 		lowest published toxic dose: 13,200 µg/kg (13-16 day pregnant) Reproductive: Effects on embryo or fetus: Cytological changes (including somatic cell genetic material) ICHUDW 4(6),24,1982
oral
mouse 		lowest published toxic dose: 9 gm/kg (6-15 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) TJADAB 19,41A,1979
oral
mouse 		lowest published toxic dose: 12 gm/kg (6-15 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants) TJADAB 19,41A,1979
oral
mouse 		lowest published toxic dose: 6,500 mg/kg (8-12 day pregnant) Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain) TCMUD8 6,361,1986
oral
mouse 		lowest published toxic dose: 16,880 mg/kg (6-15 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Effects on embryo or fetus: Fetal death 		NTIS** OTS0554056
parenteral
mouse 		lowest published toxic dose: 4 gm/kg (12 day pregnant) Reproductive: Effects on newborn: Weaning or lactation index (e.g., # alive at weaning per # alive at day 4) NEZAAQ 25,438,1970
subcutaneous
mouse 		lowest published toxic dose: 1,100 mg/kg (12 day pregnant) Reproductive: Other effects to embryo or fetus TOXID9 1,125,1981
subcutaneous
mouse 		lowest published toxic dose: 7,030 mg/kg (12-13 day pregnant) Reproductive: Effects on embryo or fetus: Extra embryonic structures (e.g., placenta, umbilical cord)

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Musculoskeletal system 		SEIJBO 15,47,1975


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
human 		lowest published toxic concentration: 10 ppm/8 hour/10 year- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Blood: Leukemia 		TRBMAV 37,153,1978
inhalation
human 		toxic concentration (other than lowest) : 150 ppm/15 minute/8 year- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Blood: Leukemia 		BLOOAW 52,285,1978
inhalation
human 		toxic concentration (other than lowest) : 8 ppb/4 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Blood: Leukemia 		NEJMAG 316,1044,1987
inhalation
human 		toxic concentration (other than lowest) : 10 mg/m3/11 year- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Blood: Leukemia 		BJIMAG 44,124,1987
inhalation
man 		lowest published toxic concentration: 200 mg/m3/78 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Blood: Leukemia

Blood: Thrombocytopenia 		EJCAAH 7,83,1971
inhalation
man 		toxic concentration (other than lowest) : 600 mg/m3/4 year- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Blood: Leukemia 		NEJMAG 271,872,1964
inhalation
man 		toxic concentration (other than lowest) : 150 ppm/11 year- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Blood: Lymphoma including Hodgkin's disease 		BLUTA9 28,293,1974
inhalation
mouse 		lowest published toxic concentration: 300 ppm/6 hour/16 week- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Blood: Lymphoma including Hodgkin's disease 		TXAPA9 75,358,1984
inhalation
mouse 		toxic concentration (other than lowest) : 1,200 ppm/6 hour/10 week- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Ear: Tumors

Lung, Thorax, or Respiration: Tumors 		PAACA3 25,75,1984
inhalation
mouse 		toxic concentration (other than lowest) : 300 ppm/6 hour/16 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Blood: Leukemia 		IHRMEQ (3),156,1984
inhalation
rat 		lowest published toxic concentration: 1,200 ppm/6 hour/10 week- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Ear: Tumors 		PAACA3 25,75,1984
intraperitoneal
mouse 		lowest published toxic dose: 1,200 mg/kg/8 week- intermittent Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		TXAPA9 82,19,1986
oral
mouse 		lowest published toxic dose: 18,250 mg/kg/2 year- continuous Tumorigenic: Carcinogenic by RTECS criteria

Endocrine: Tumors

Blood: Lymphoma including Hodgkin's disease 		NTPTR* NTP-TR-289,1986
oral
mouse 		toxic dose : 2,400 mg/kg/8 week- intermittent Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		TXAPA9 82,19,1986
oral
mouse 		lowest published toxic dose: 12,875 mg/kg/103 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Liver: Tumors

Blood: Lymphoma including Hodgkin's disease 		NTIS** PB86-216967/AS
oral
mouse 		lowest published toxic dose: 51,500 mg/kg/103 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Endocrine: Tumors 		NTIS** PB86-216967/AS
oral
rat 		lowest published toxic dose: 52 gm/kg/52 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Endocrine: Tumors

Blood: Leukemia 		MELAAD 70,352,1979
oral
rat 		toxic dose : 52 gm/kg/1 year- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Ear: Tumors

Blood: Leukemia 		AJIMD8 4,589,1983
oral
rat 		toxic dose : 10 gm/kg/52 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Endocrine: Tumors

Blood: Leukemia 		MELAAD 70,352,1979
oral
rat 		lowest published toxic dose: 51,500 mg/kg/103 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Endocrine: Tumors 		NTIS** PB86-216967/AS
oral
rat 		lowest published toxic dose: 103,000 mg/kg/103 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Skin and Appendages: Tumors 		NTIS** PB86-216967/AS
oral
rat 		lowest published toxic dose: 12,875 mg/kg/103 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Gastrointestinal: Tumors

Endocrine: Tumors 		NTIS** PB86-216967/AS
parenteral
mouse 		lowest published toxic dose: 670 mg/kg/19 week- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Blood: Leukemia

Blood: Lymphoma including Hodgkin's disease 		KLWOAZ 12,109,1933
subcutaneous
mouse 		lowest published toxic dose: 600 mg/kg/17 week- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Blood: Leukemia

Blood: Lymphoma including Hodgkin's disease 		KRANAW 9,403,1932
skin
mouse 		lowest published toxic dose: 1,200 gm/kg/49 week- intermittent Tumorigenic: Neoplastic by RTECS criteria

Skin and Appendages: Tumors 		BJCAAI 16,275,1962


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
cat 		lowest published lethal concentration: 170,000 mg/m3 N/R HBTXAC 1,324,1955
inhalation
dog 		lowest published lethal concentration: 146,000 mg/m3 N/R HBTXAC 1,324,1955
inhalation
human 		lowest published lethal concentration: 2 pph/5 minute N/R TABIA2 3,231,1933
inhalation
human 		lowest published toxic concentration: 100 ppm Behavioral: Somnolence (general depressed activity)

Gastrointestinal: Nausea or vomiting

Skin: After systemic exposure: Dermatitis, other 		INMEAF 17,199,1948
inhalation
human 		lowest published lethal concentration: 65 mg/m3/5 year Blood: Other changes ARGEAR 44,145,1974
inhalation
human 		lowest published toxic concentration: 50 mg/m3/2 hour Behavioral: Change in psychophysiological tests

Behavioral: Muscle weakness 		VCVGH* -,120,1990
inhalation
human 		lowest published toxic concentration: 75 mg/m3/2 hour Blood: Changes in other cell count (unspecified)

Blood: Changes in leukocyte (WBC) count 		VCVGH* -,120,1990
inhalation
human 		lowest published lethal concentration: 2 pph/2 minute N/R VCVGH* -,121,1990
inhalation
human 		lowest published lethal concentration: 5 mg/m3/5 hour N/R VCVGH* -,121,1990
inhalation
mammal (species unspecified) 		lowest published lethal concentration: 20,000 ppm/5 minute N/R AEPPAE 138,65,1928
inhalation
man 		lowest published toxic concentration: 150 ppm/1 year- intermittent Blood: Other changes

Nutritional and Gross Metabolic: Body temperature increase 		BLUTA9 28,293,1974
inhalation
mouse 		lethal concentration (50 percent kill): 9,980 ppm Behavioral: General anesthetic

Behavioral: Muscle weakness

Lung, Thorax, or Respiration: Dyspnea 		JIHTAB 25,366,1943
inhalation
mouse 		lethal concentration (10 percent kill): 15 mL/kg/2 hour N/R VCVGH* -,119,1990
inhalation
mouse 		lowest published toxic concentration: 2,000 ppm/30 minute Behavioral: Change in motor activity (specific assay) TXAPA9 193,9,2003
inhalation
mouse 		lowest published toxic concentration: 3,013 ppm/30 minute Behavioral: Change in motor activity (specific assay)

Behavioral: Alteration of classical conditioning 		TXAPA9 193,9,2003
inhalation
rat 		lethal concentration (50 percent kill): 10,000 ppm/7 hour N/R 28ZRAQ -,113,1960
inhalation
rat 		lowest published toxic concentration: 4,000 ppm Behavioral: General anesthetic VCVGH* -,119,1990
inhalation
rat 		lowest published lethal concentration: 10,000 ppm N/R VCVGH* -,119,1990
inhalation
rat 		lowest published toxic concentration: 16.7 gm/m3/2 hour Gastrointestinal: Changes in structure or function of exocrine pancreas VCVGH* -,120,1990
inhalation
rat 		lowest published toxic concentration: 1 ppm/6 hour Kidney, Ureter, and Bladder: Other changes in urine composition FCTOD7 40,1799,2002
inhalation
rabbit 		lowest published lethal concentration: 45,000 ppm/30 minute N/R JIHTAB 26,69,1944
inhalation
rabbit 		lowest published lethal concentration: 35,000 ppm/22 minute Brain and Coverings: Other degenerative changes

Behavioral: Tremor

Eye: Other eye effects 		VCVGH* -,119,1990
intramuscular
rabbit 		lowest published lethal dose: 0.1 mL/kg Brain and Coverings: Recordings from specific areas of CNS

Blood: Other hemolysis with or without anemia 		VCVGH* -,119,1990
intraperitoneal
guinea pig 		lowest published lethal dose: 527 mg/kg N/R HBTXAC 1,42,1955
intraperitoneal
mammal (species unspecified) 		lowest published lethal dose: 1,500 mg/kg Peripheral Nerve and Sensation: Flaccid paralysis without anesthesia (usually neuromuscular blockage)

Behavioral: Convulsions or effect on seizure threshold

Behavioral: Irritability 		AJHYA2 7,276,1927
intraperitoneal
mouse 		lethal dose (50 percent kill): 340 mg/kg N/R ANYAA9 243,104,1975
intraperitoneal
rat 		lethal dose (50 percent kill): 1,100 µg/kg N/R APYPAY 12,173,1961
intravenous
rabbit 		lowest published lethal dose: 88 mg/kg Peripheral Nerve and Sensation: Spastic paralysis with/without sensory change

Eye: Hemorrhage

Gastrointestinal: Gastritis 		JTEHD6 (Suppl 2),45,1977
oral
dog 		lowest published lethal dose: 2 gm/kg N/R HBAMAK 4,1313,1935
oral
human 		lowest published lethal dose: 0.7 mL/kg N/R VCVGH* -,122,1990
oral
mammal (species unspecified) 		lethal dose (50 percent kill): 5,700 mg/kg N/R GISAAA 39(4),86,1974
oral
man 		lowest published lethal dose: 50 mg/kg N/R YAKUD5 22,883,1980
oral
mouse 		lethal dose (50 percent kill): 4,700 mg/kg N/R HYSAAV 32(3),349,1967
oral
mouse 		lowest published toxic dose: 880 mg/kg/12 hour Blood: Changes in bone marrow not included in above MUREAV 208,61,1988
oral
rat 		lethal dose (50 percent kill): 930 mg/kg Behavioral: Tremor

Behavioral: Convulsions or effect on seizure threshold 		TXAPA9 7,767,1965
oral
rat 		lethal dose (50 percent kill): 1 mL/kg N/R VCVGH* -,119,1990
oral
rat 		lethal dose (50 percent kill): 1,800 mg/kg N/R VCVGH* -,119,1990
subcutaneous
frog 		lowest published lethal dose: 1,400 mg/kg N/R HBAMAK 4,1313,1935
subcutaneous
rat 		lowest published lethal dose: 5 mg/kg Behavioral: Tremor NTIS** OTS0544815
skin
guinea pig 		lethal dose (50 percent kill): >9,400 µL/kg N/R TXAPA9 7,559,1965
skin
mouse 		lethal dose (50 percent kill): 48 mg/kg N/R NPIRI* 1,5,1974
skin
rabbit 		lethal dose (50 percent kill): >9,400 µL/kg N/R TXAPA9 7,559,1965
unreported route
man 		lowest published lethal dose: 194 mg/kg N/R 85DCAI 2,73,1970


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
mouse 		lowest published toxic concentration: 300 ppm/6 hour/13 week- intermittent Blood: Normocytic anemia

Blood: Thrombocytopenia

Related to Chronic Data: Changes in testicular weight 		AJIMD8 7,457,1985
inhalation
mouse 		lowest published toxic concentration: 25 ppm/6 hour/5 day- intermittent Endocrine: Changes in spleen weight

Blood: Changes in leukocyte (WBC) count 		TOLED5 56,159,1991
inhalation
mouse 		lowest published toxic concentration: 10 ppm/6 hour/10 week- intermittent Endocrine: Changes in spleen weight

Blood: Changes in spleen 		TXAPA9 58,492,1981
inhalation
mouse 		lowest published toxic concentration: 10 ppm/6 hour/26 week- intermittent Blood: Changes in spleen

Blood: Changes in other cell count (unspecified)

Blood: Changes in erythrocyte (RBC) count 		TOLED5 20,337,1984
inhalation
mouse 		lowest published toxic concentration: 300 ppm/6 hour/16 week- intermittent Blood: Changes in bone marrow not included in above

Blood: Changes in other cell count (unspecified)

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		AJIMD8 7,447,1985
inhalation
mouse 		lowest published toxic concentration: 48 ppm/6 hour/14 day- intermittent Blood: Luekopenia

Endocrine: Changes in spleen weight

Immunological Including Allergic: Decrease in humoral immune response 		TXAPA9 85,92,1986
inhalation
mouse 		lowest published toxic concentration: 100 ppm/6 hour/72 week- intermittent Blood: Normocytic anemia

Blood: Luekopenia

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		TXAPA9 54,323,1980
inhalation
mouse 		lowest published toxic concentration: 100 ppm/6 hour/2 week- intermittent Blood: Changes in leukocyte (WBC) count TOXID9 72,228,2003
inhalation
mouse 		lowest published toxic concentration: 100 ppm/2 week- intermittent Endocrine: Differential effect of sex or castration on observed toxicity

Blood: Luekopenia

Blood: Changes in bone marrow not included in above 		TOSCF2 72,201,2003
inhalation
pig 		lowest published toxic concentration: 100 ppm/6 hour/3 week- intermittent Kidney, Ureter, and Bladder: Other changes in urine composition

Blood: Pigmented or nucleated red blood cells

Blood: Changes in bone marrow not included in above 		JTEHD6 5,1025,1979
inhalation
rat 		lowest published toxic concentration: 23 mg/m3/4 hour/8 day- intermittent Liver: Changes in liver weight

Endocrine: Changes in pituitary weight 		TPKVAL 12,5,1971
inhalation
rat 		lowest published toxic concentration: 300 ppm/6 hour/13 week- intermittent Blood: Luekopenia AJIMD8 7,457,1985
inhalation
rat 		lowest published toxic concentration: 300 ppm/6 hour/99 week- intermittent Blood: Luekopenia

Blood: Changes in bone marrow not included in above

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		JTEHD6 4,605,1978
inhalation
rat 		lowest published toxic concentration: 1,000 ppm/7 hour/28 week- intermittent Blood: Changes in other cell count (unspecified) JIHTAB 26,37,1944
inhalation
rat 		lowest published toxic concentration: 500 ppm/6 hour/3 week- intermittent Blood: Pigmented or nucleated red blood cells

Blood: Changes in bone marrow not included in above

Blood: Changes in leukocyte (WBC) count 		JTEHD6 5,1025,1979
inhalation
rat 		lowest published toxic concentration: 1,172 mg/m3/2 week- intermittent Liver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.) 		TXCYAC 188,161,2003
inhalation
rabbit 		lowest published toxic concentration: 500 mg/m3/3 hour/13 week- intermittent Blood: Hemorrhage

Blood: Other changes

Lung, Thorax, or Respiration: Other changes 		GISAAA 24(1),80,1959
intraperitoneal
rat 		lowest published toxic dose: 5 mL/kg/10 day- intermittent Liver: Other changes

Nutritional and Gross Metabolic: Changes in: Fe 		IJEBA6 36,283,1998
intraperitoneal
rat 		lowest published toxic dose: 159.9 µg/kg/3 day- intermittent Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Cytochrome oxidases (indlucing oxidative phosphrylation) 		TOLED5 144,55,2003
intraperitoneal
rat 		lowest published toxic dose: 24.97 µg/kg/2 day- intermittent Liver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Cytochrome oxidases (indlucing oxidative phosphrylation) 		TOLED5 144,55,2003
oral
mouse 		lowest published toxic dose: 4,250 mg/kg/17 week- intermittent Blood: Other changes

Blood: Changes in leukocyte (WBC) count 		NTPTR* NTP-TR-289,1986
oral
mouse 		lowest published toxic concentration: 211 ppm/6 hour/7 day- intermittent Blood: Luekopenia

Endocrine: Changes in spleen weight

Blood: Changes in leukocyte (WBC) count 		TXAPA9 85,92,1986
oral
mouse 		lowest published toxic dose: 929.6 mg/kg/4 week- continuous Brain and Coverings: Other degenerative changes

Blood: Changes in spleen

Immunological Including Allergic: Decrease in cellular immune response 		IMMPH* 21,23,1991
oral
mouse 		lowest published toxic dose: 232.4 mg/kg/7 day- continuous Endocrine: Adrenal cortex hyperplasia IMMPH* 21,23,1991
oral
rat 		lowest published toxic dose: 6,600 mg/kg/27 week- intermittent Blood: Luekopenia

Blood: Changes in erythrocyte (RBC) count 		AMIHAB 14,387,1956
oral
rat 		lowest published toxic dose: 17 gm/kg/17 week- intermittent Blood: Changes in spleen

Blood: Changes in leukocyte (WBC) count 		NTPTR* NTP-TR-289,1986
subcutaneous
mouse 		lowest published toxic dose: 2,197 mg/kg/5 day- intermittent Endocrine: Changes in spleen weight

Endocrine: Changes in thymus weight

Blood: Changes in leukocyte (WBC) count 		INHEAO 3,91,1965
subcutaneous
mouse 		lowest published toxic dose: 4,000 mg/kg/5 day- intermittent Blood: Other changes

Immunological Including Allergic: Decrease in cellular immune response 		TXAPA9 103,198,1990
subcutaneous
rat 		lowest published toxic dose: 12 gm/kg/6 week- intermittent Blood: Changes in bone marrow not included in above

Blood: Changes in other cell count (unspecified)

Blood: Changes in leukocyte (WBC) count 		TOLED5 109(Suppl 1),32,1999
subcutaneous
rat 		lowest published toxic dose: 18 mg/kg/21 day- intermittent Blood: Changes in erythrocyte (RBC) count

Blood: Changes in leukocyte (WBC) count

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		AJHYA2 7,276,1927
subcutaneous
rat 		lowest published toxic dose: 2,197 mg/kg/5 day- intermittent Blood: Pigmented or nucleated red blood cells

Blood: Changes in leukocyte (WBC) count

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		INHEAO 3,91,1965
subcutaneous
rat 		lowest published toxic dose: 13,536 mg/kg/12 week- intermittent Liver: Other changes

Kidney, Ureter, and Bladder: Other changes in urine composition

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other hydrolases 		BCTKAG 17,101,1984
subcutaneous
rat 		lowest published toxic dose: 7.5 mL/kg/12 week- intermittent Liver: Other changes

Blood: Luekopenia

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects 		TCMUD8 20,329,2000


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value time-weighted average 0.5 ppm (skin) DTLVS* TLV/BEI,2003
American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value Confirmed Human Carcinogen DTLVS* TLV/BEI,2003
American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value short term exposure limit 2.5 ppm (skin) DTLVS* TLV/BEI,2003
International Agency for Research on Cancer (IARC) Cancer Review Human Limited Evidence IMEMDT 7,203,1974
International Agency for Research on Cancer (IARC) Cancer Review Animal Sufficient Evidence IMSUDL 7,120,1987
International Agency for Research on Cancer (IARC) Cancer Review Animal Limited Evidence IMEMDT 29,93,1982
International Agency for Research on Cancer (IARC) Cancer Review Human Sufficient Evidence IMEMDT 29,93,1982
International Agency for Research on Cancer (IARC) Cancer Review Animal Inadequate Evidence IMEMDT 7,203,1974
International Agency for Research on Cancer (IARC) Cancer Review Group 1 IMSUDL 7,120,1987
TOXICOLOGY REVIEW
CRTXB2 32,1,2002
TOXICOLOGY REVIEW
MUREAV 566,99,2004
TOXICOLOGY REVIEW
MUREAV 566,21,2004
TOXICOLOGY REVIEW
TOLED5 127,111,2002
TOXICOLOGY REVIEW
FNSCA6 2,67,1973
TOXICOLOGY REVIEW
MUREAV 47,75,1978
TOXICOLOGY REVIEW
AMSVAZ 118,354,1944
TOXICOLOGY REVIEW
ZHPMAT 166,113,1978
TOXICOLOGY REVIEW
JTEHD6 (Suppl 2),69,1977
TOXICOLOGY REVIEW
PHRPA6 41,1357,1926
TOXICOLOGY REVIEW
AIHAAP 41,616,1980
TOXICOLOGY REVIEW
CTOXAO 11,531,1977
TOXICOLOGY REVIEW
BNYMAM 54,413,1978
TOXICOLOGY REVIEW
KRANAW 9,403,1932
TOXICOLOGY REVIEW
JTEHD6 61,339,2000
TOXICOLOGY REVIEW
JTEHD6 61,353,2000
TOXICOLOGY REVIEW
TOLED5 134,3,2002
TOXICOLOGY REVIEW
MUREAV 543,201,2003
TOXICOLOGY REVIEW
TOLED5 140-141,353,2003
TOXICOLOGY REVIEW
MUREAV 5432012003
TOXICOLOGY REVIEW
MUREAV 567,227,2004
TOXICOLOGY REVIEW
MUREAV 567,109,2004
TOXICOLOGY REVIEW
MUREAV 567,151,2004


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
Mine Safety and Health Administration (MSHA) STANDARD air-ceiling concentration 25 ppm (80 mg/m3) (skin) DTLVS* 3,22,1971
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Construction) see Code of Federal Regulations (CFR) 29,1926.1128 CFRGBR 29,1926.55,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Federal Contractors) ceiling concentration 25 ppm (80 mg/m3) (skin) CFRGBR 41,50-204.50,1994
Occupational Safety and Health Administration (OSHA) cancer hazard FEREAC 52,34460,1987
Occupational Exposure Limit - AUSTRALIA time-weighted average 5 ppm (16 mg/m3), Carcinogen, JAN1993
Occupational Exposure Limit - AUSTRIA Skin, Carcinogen, JAN1999
Occupational Exposure Limit - BELGIUM time-weighted average 10 ppm (32 mg/m3), Carcinogen, JAN1993
Occupational Exposure Limit - DENMARK time-weighted average 5 ppm (16 mg/m3), Skin, JAN1999
Occupational Exposure Limit - FINLAND time-weighted average 5 ppm (15 mg/m3), short term exposure limit 10 ppm (30 mg/m3), Skin, Carcinogen, JAN1993
Occupational Exposure Limit - UNITED KINGDOM time-weighted average 3 ppm (9.6 mg/m3), Carcinogen, SEP2000
Occupational Exposure Limit - GERMANY Skin, Carcinogen, JAN1999
Occupational Exposure Limit - HUNGARY short term exposure limit 5 mg/m3, Skin, Carcinogen, JAN1993
Occupational Exposure Limit - THE NETHERLANDS MAC-TGG 3.25 mg/m3, Skin, 2003
Occupational Exposure Limit - JAPAN Occupational Exposure Limit 10 ppm (32 mg/m3), Group 1 Carcinogen, JAN1999
Occupational Exposure Limit - NORWAY time-weighted average 1 ppm (3 mg/m3), JAN1999
Occupational Exposure Limit - THE PHILIPPINES time-weighted average 25 ppm (80 mg/m3), Skin, JAN1993
Occupational Exposure Limit - POLAND MAC(time-weighted average) 10 mg/m3, MAC(short term exposure limit) 40 mg/m3, JAN1999
Occupational Exposure Limit - RUSSIA time-weighted average 10 ppm (5 mg/m3), short term exposure limit 25 ppm (15 mg/m3), Skin, Carcinogen, JAN1993
Occupational Exposure Limit - SWEDEN NGV 0.5 ppm (1.5 mg/m3), KTV 3 ppm (9 mg/m3), Skin, Carcinogen, JAN1999
Occupational Exposure Limit - SWITZERLAND MAK- week 1 ppm (3.2 mg/m3), Skin, Carcinogen, JAN1999
Occupational Exposure Limit - THAILAND time-weighted average 10 ppm (30 mg/m3), short term exposure limit 25 ppm (75 mg/m3), JAN1993
Occupational Exposure Limit - TURKEY time-weighted average 20 ppm (64 mg/m3), Skin, JAN1993
Occupational Exposure Limit - UNITED KINGDOM LTEL 10 ppm (30 mg/m3), JAN1993
Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN, KOREA American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value;

short term exposure limit 2.5 ppm (skin)
Occupational Exposure Limit IN NEW ZEALAND, SINGAPORE, VIETNAM American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value
short term exposure limit 2.5 ppm (skin)


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO BENZENE-air Carcinogen;
8 hour time-weighted average 0.1 ppm;
ceiling concentration 1 ppm/15 minute 		NIOSH* DHHS #92-100,1992
National Occupational Hazard Survey 1974 National Occupational Hazard Survey 1974: Hazard Code: 09070;
Number of Industries 126;
Total Number of Facilities 11,184;
Number of Occupations 106;
Total Number of Employees Exposed 147,583
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: 09070;
Number of Industries 92;
Total Number of Facilities 10,054;
Number of Occupations 117;
Total Number of Employees Exposed 272,275;
Total Number of Female Employees Exposed 143,066


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
ATSDR TOXICOLOGY PROFILE (NTIS** PB/98/101157/AS)
EPA GENETOX PROGRAM 1988, Positive: Carcinogenicity-mouse/rat
EPA GENETOX PROGRAM 1988, Positive: In vitro cytogenetics-human lymphocyte
EPA GENETOX PROGRAM 1988, Positive: In vivo cytogenetics-human lymphocyte
EPA GENETOX PROGRAM 1988, Positive: Mammalian micronucleus; Sperm morphology-mouse
EPA GENETOX PROGRAM 1988, Negative: Cell transform.-SA7/SHE; In vitro SCE-human lymphocytes
EPA GENETOX PROGRAM 1988, Negative: In vitro SCE-human
EPA TSCA Section 8(b) CHEMICAL INVENTORY
Used in blends with gasoline, and in the manufacture of CYCLOHEXANE and ETHYLBENZENE
EPA TSCA Section 8(d) unpublished health/safety studies
On EPA IRIS database
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001
NIOSH Analytical Method, 1994: Hydrocarbons, BP 36-126 degree C, 1500
NIOSH Analytical Method, 1994: Benzene, by portable GC, 3700
NIOSH Analytical Method, 1994: Hydrocarbons, aromatic, 1501
NCI Carcinogenesis Studies (gavage);clear evidence:mouse,rat
NTP 11th Report on Carcinogens,2004:Known to be human carcinogen
NTP Carcinogenesis studies; on test (prechronic studies), October 2000
OSHA ANALYTICAL METHOD #12


REFERENCES:

CODEN
REFERENCE
28ZRAQ "Toxicology and Biochemistry of Aromatic Hydrocarbons," Gerarde, H., New York, Elsevier, 1960
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VCVGH* "Vrednie chemichescie veshestva, galogenproisvodnie uglevodorodov". (Hazardous substances: Galogenated hydrocarbons) Bandman A.L. et al., Chimia, 1990.
YAKUD5 Gekkan Yakuji. Pharmaceuticals Monthly. (Yakugyo Jihosha, Inaoka Bldg., 2-36 Jinbo-cho, Kanda, Chiyoda-ku, Tokyo 101, Japan) V.1- 1959-
ZHPMAT Zentralblatt fuer Bakteriologie, Parasitenkunde, Infektionskrankheiten und Hygiene, Abteilung 1: Originale, Reihe B: Hygiene, Krankenhaushygiene, Betriebshygiene, Praeventive Medizin. (Stuttgart, Fed. Rep. Ger.) V.155-169, 1971-1979. For publisher information, see ZAOMDC.

Used in blends with gasoline, and in the manufacture of CYCLOHEXANE and ETHYLBENZENE

Top 50 chemical production: 12.01 billions lbs in 1992, 11.49 billions in 1991

NIOSH PROFILE (PAINT AND ALLIED PRODUCTS MANUFACTURING), FIRL, 4/78

NIOSH PROFILE (PETROCHEMICAL PLANTS), FIRL, 4/78

NIOSH PROFILE (PETROLEUM REFINING), FIRL, 4/78

NIOSH PROFILE (SPRAY PAINTING), FIRL, 4/78

NIOSH PROFILE (PAINT AND ALLIED PRODUCTS MANUFACTURING), SRI, 2/7

RTECS Compound Description:
   Agricultural Chemical
   Tumorigen
   Drug
   Mutagen
   Reproductive Effector
   Human Data
   Primary Irritant

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