Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F sub 1 mice
- National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)
- Environmental Protection Agency, Research Triangle Park, NC (USA)
- Battelle Columbus Division, OH (USA)
- Univ. of Michigan, Ann Arbor (USA)
- Carltech Associates, Rockville, MD (USA)
Toxicology and carcinogenesis studies of benzene were conducted in groups of 60 F344/N rats and 60 B6C3F{sub 1} mice of each sex for each of three exposure doses and vehicle controls. Using the results from 17-week studies, doses for the 2-year studies were selected based on clinical observations, on clinical pathologic findings and on body weight effects. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil were administered by gavage to male rats, 5 days per week, for 103 weeks. 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 weeks. Ten animals in each of the 16 groups were killed at 12 months, and necropsies were performed. Hematologic profiles were performed at 3-month intervals. For the 2-year studies, mean body weights of the top dose groups of male rats and of both sexes of mice were lower than those of the controls. Survivals of the top dose group of rats and mice of each sex were reduced; however, at week 92 for rats and week 91 for mice, survival was greater than 60% in all groups; most of the dosed animals that died before week 103 had neoplasia. Compound-related nonneoplastic or neoplastic effects on the hematopoietic system, Zymbal gland, forestomach, and adrenal gland were found both for rats and mice. Further, the oral cavity was affected in rats, and the lung, liver, Harderian gland, preputial gland, ovary, and mammary gland were affected in mice. Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenicity of benzene in male F344/N rats, female F344/N rats, male B6C3F{sub 1} mice, and female B6C3F{sub 1} mice. Dose-related lymphocytopenia was observed for male and female F344/N rats and male and female B6C3F{sub 1} mice. These unequivocal observations show clearly that benzene is a trans-species, trans-sex, multisite potent carcinogen.
- OSTI ID:
- 7150296
- Journal Information:
- Environmental Health Perspectives; (USA), Vol. 82; ISSN 0091-6765
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BENZENE
BIOLOGICAL EFFECTS
CARCINOGENESIS
RISK ASSESSMENT
ADRENAL GLANDS
CHROMOSOMAL ABERRATIONS
EXCRETION
HEMATOPOIETIC SYSTEM
LUNGS
LYMPHOPENIA
METABOLISM
METABOLITES
MICE
RATS
SAFETY STANDARDS
SISTER CHROMATID EXCHANGES
STOMACH
ANIMALS
AROMATICS
BODY
CLEARANCE
DIGESTIVE SYSTEM
DISEASES
ENDOCRINE GLANDS
GASTROINTESTINAL TRACT
GLANDS
HEMIC DISEASES
HYDROCARBONS
IMMUNE SYSTEM DISEASES
LEUKOPENIA
MAMMALS
MUTATIONS
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
RESPIRATORY SYSTEM
RODENTS
STANDARDS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology