Species differences in the metabolism and disposition of inhaled 1,3-butadiene and isoprene

Journal Article · Fri Jun 01 00:00:00 EDT 1990 · Environmental Health Perspectives; (USA)

DOI:https://doi.org/10.1289/ehp.908665· OSTI ID:5718674

Dahl, A R; Bechtold, W E; Bond, J A; Henderson, R F; Mauderly, J L; Muggenburg, B A; Sun, J D ^[1]; Birnbaum, L S ^[2]

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1. Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM (USA)
2. National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)

Species differences in sensitivity to carcinogenic effects from inhaled 1,3-butadiene might stem, at least in part, from differences in uptake, metabolism, and distribution of 1,3-butadiene. To examine this possibility, rats, mice, and monkeys were exposed to stepped concentrations of {sup 14}C-labeled 1,3-butadiene and the chemically related compound, isoprene. Respiratory data were collected during exposure and were used to determine fractional uptake. Rates and routes of excretion of retained radioactivity were also determined and blood levels of potentially toxic metabolites were measured. Some results from these continuing studies to date are: (a) mice achieve higher blood concentrations of reactive metabolites than do rats; (b) blood levels of toxic metabolites are lower in monkeys than in rodents; (c) uptake and retention of 1,3-butadiene is nonlinear in the range where long-term toxicity studies have been conducted; (d) the efficiency of production of reactive metabolites decreases with increased inhaled concentrations of 1,3-butadiene; (e) repeated exposure to 1,3-butadiene does not induce the metabolism of 1,3-butadiene in rodents; (f) hemoglobin adducts of 1,3-butadiene are potential dosimeters of exposure; and (g) rats inhaling isoprene produce reactive metabolites analogous to those produced during inhalation of 1,3-butadiene. The availability data indicate that major differences in the biological fate of inhaled 1,3-butadiene occur among species, and these differences, at least in part, account for those in species sensitivity to the toxicity of inhaled 1,3-butadiene.

• DOE Contract Number: AC04-76EV01013
• OSTI ID: 5718674
• Journal Information: Environmental Health Perspectives; (USA), Vol. 86; ISSN 0091-6765
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BUTADIENE
METABOLISM
CARBON 14 COMPOUNDS
PHARMACOLOGY
ISOPRENE
DOSE-RESPONSE RELATIONSHIPS
EXCRETION
HEMOGLOBIN
INHALATION
LUNGS
MICE
MONKEYS
RATS
TOXICITY
ANIMALS
BODY
CARBOXYLIC ACIDS
CLEARANCE
DIENES
GLOBINS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
INTAKE
LABELLED COMPOUNDS
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PIGMENTS
POLYENES
PORPHYRINS
PRIMATES
PROTEINS
RESPIRATORY SYSTEM
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology