Disposition of inhaled isoprene in B6C3F1 mice

Journal Article · Fri Mar 01 04:00:00 EST 1991 · Toxicology and Applied Pharmacology; (USA)

DOI:https://doi.org/10.1016/0041-008X(91)90312-3· OSTI ID:5922056

Bond, J A; Bechtold, W E; Birnbaum, L S; Dahl, A R; Medinsky, M A; Sun, J D; Henderson, R F ^[1]

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1. Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM (USA)

Isoprene (2-methyl-1,3-butadiene) is the monomeric unit of widely occurring natural products called terpenes. Isoprene is widely used in industry with nearly 1.1 million pounds produced in the United States in 1987. The purpose of this investigation was to determine the toxicokinetics of inhaled isoprene in B6C3F1 mice and to compare the data to previously published toxicokinetic data in F344 rats. The comparative toxicokinetics in the two species will be useful for extrapolation of rodent toxicity data to humans. Male B6C3F1 mice were exposed to nominal concentrations of 20, 200, and 2000 ppm isoprene or (14C)isoprene for up to 6 hr. For all exposures, steady-state levels of isoprene were reached rapidly (i.e., within 15 to 30 min) after the onset of exposure. The mean (+/- SE) steady-state blood levels of isoprene (identified by headspace analysis) for the 20, 200, and 2000 ppm exposures were 24.8 +/- 3.3, 830 +/- 51, and 6800 +/- 400 ng isoprene/ml blood, respectively. At the two higher exposure concentrations, the increases in blood levels of isoprene were proportional to the increases in air concentrations of isoprene. There was approximately a 2.3-fold decrease in the retained 14C/inhaled 14C ratio with increasing exposure concentration. Depending on the exposure concentration, from 52% (20 ppm isoprene) to 73% (2000 ppm isoprene) of the metabolite-associated (nonisoprene) radioactivity was excreted in the urine over a 64-hr postexposure period. 14CO2 exhalation after the end of the 6-hr exposure was minimal (2%) at the 20 ppm exposure and increased up to 18% at the higher isoprene exposure concentrations. These data suggest that metabolism of isoprene in mice is nonlinear within the range of exposure concentrations used in this study.

• OSTI ID: 5922056
• Journal Information: Toxicology and Applied Pharmacology; (USA), Journal Name: Toxicology and Applied Pharmacology; (USA) Vol. 107:3; ISSN TXAPA; ISSN 0041-008X
• Country of Publication: United States
• Language: English

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.
ANIMALS
BIOLOGICAL VARIABILITY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
COMPARATIVE EVALUATIONS
DIENES
GENETIC VARIABILITY
GLOBINS
HEMOGLOBIN
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
INHALATION
INTAKE
ISOPRENE
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
METABOLISM
MICE
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PIGMENTS
POLYENES
PORPHYRINS
PROTEINS
RATS
RESPIRATION
RODENTS
TOXICITY
TRACER TECHNIQUES
VERTEBRATES