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Differences in the metabolism and disposition of inhaled (3H)benzene by F344/N rats and B6C3F1 mice

Journal Article · · Toxicol. Appl. Pharmacol.; (United States)
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Benzene is a potent hematotoxin and has been shown to cause leukemia in man. Chronic toxicity studies indicate that B6C3F1 mice are more susceptible than F334/N rats to benzene toxicity. The purpose of the studies presented in this paper was to determine if there were metabolic differences between F344/N rats and B6C3F1 mice which might be responsible for this increased susceptibility. Metabolites of benzene in blood, liver, lung, and bone marrow were measured during and following a 6-hr 50 ppm exposure to benzene vapor. Hydroquinone glucuronide, hydroquinone, and muconic acid, which reflect pathways leading to potential toxic metabolites of benzene, were present in much greater concentrations in the mouse than in rat tissues. Phenylsulfate, a detoxified metabolite, and an unknown water-soluble metabolite were present in approximately equal concentrations in these two species. These results indicate that the proportion of benzene metabolized via pathways leading to the formation of potentially toxic metabolites as opposed to detoxification pathways was much higher in B6C3F1 mice than in F344 rats, which may explain the higher susceptibility of mice to benzene-induced hematotoxicity and carcinogenicity.

Research Organization:
Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM (USA)
OSTI ID:
6922262
Journal Information:
Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 94:1; ISSN TXAPA
Country of Publication:
United States
Language:
English

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Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL TISSUES
ANIMALS
AROMATICS
BENZENE
BIOLOGICAL PATHWAYS
BIOLOGICAL VARIABILITY
BODY
BONE MARROW
CARBOXYLIC ACIDS
DIGESTIVE SYSTEM
GENETIC VARIABILITY
GLANDS
HEMATOPOIETIC SYSTEM
HYDROCARBONS
INHALATION
INTAKE
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
MAMMALS
METABOLISM
METABOLITES
MICE
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
RATS
RODENTS
SORBIC ACID
SULFATES
SULFUR COMPOUNDS
TISSUES
TOXICITY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES