Comparison of the disposition and in vitro metabolism of 4-vinylcyclohexene in the female mouse and rat

Journal Article · Sat Sep 15 00:00:00 EDT 1990 · Toxicology and Applied Pharmacology; (USA)

DOI:https://doi.org/10.1016/0041-008X(90)90140-P· OSTI ID:6318170

Smith, B J; Carter, D E; Sipes, I G ^[1]

---

1. Univ. of Arizona, Tucson (USA)

4-Vinylcyclohexene (VCH) is a chemical to which humans are exposed in the rubber industry. A chronic carcinogenicity bioassay conducted by the National Toxicology Program showed that oral administration of VCH induced tumors in the ovaries of mice but not in those of rats. The hypothesis tested was that the species and organ specificity of VCH toxicity was due to differences in the disposition of VCH between the female rat and mouse. Therefore, the disposition of a single oral dose of 400 mg/kg (14C)VCH was studied in female B6C3F1 mice and Fischer 344 rats. Mice eliminated greater than 95% of the dose in 24 hr, whereas rats required 48 hr to eliminate greater than 95% of the dose. The major routes of excretion of (14C)VCH-derived radioactivity were in the urine (50-60%) and expired air (30-40%). No evidence was obtained to indicate that the ovaries of either species retained VCH as a parent compound or as radioactive equivalents. A dramatic difference was observed between the rat and mouse in the appearance of a monoepoxide of VCH in blood from 0.5 to 6 hr after VCH administration (800 mg/kg, ip). VCH-1,2-epoxide was present in the blood of mice with the highest concentration at 2 hr (41 nmol/ml). The blood concentration of VCH-1,2-epoxide in rats was less than 2.5 nmol/ml at all times examined. VCH-7,8-epoxide was not present in the blood of either species at the level of detection. These findings were supported by in vitro studies of VCH epoxidation by liver microsomes. The rate of epoxidation of VCH (1 mM) to VCH-1,2-epoxide was 6.5-fold greater in mouse liver microsomes than that in rat liver microsomes. The species difference in the rate of epoxide formation by the liver may be an important factor in the species difference in susceptibility to VCH-induced ovarian tumors.

• OSTI ID: 6318170
• Journal Information: Toxicology and Applied Pharmacology; (USA), Journal Name: Toxicology and Applied Pharmacology; (USA) Vol. 105:3; 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.
ALKENES
ANIMALS
BIOLOGICAL VARIABILITY
BODY
CARBON 14 COMPOUNDS
CARCINOGEN SCREENING
CELL CONSTITUENTS
DIGESTIVE SYSTEM
DISTRIBUTION
EXPERIMENTAL NEOPLASMS
FEMALE GENITALS
GENETIC VARIABILITY
GLANDS
GONADS
HEXENES
HYDROCARBONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
MAMMALS
METABOLISM
MICE
MICROSOMES
ORAL ADMINISTRATION
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
OVARIES
RATS
RIBOSOMES
RODENTS
SCREENING
TISSUE DISTRIBUTION
TRACER TECHNIQUES
VERTEBRATES