Biomaterial Database

Pharmacokinetics of vinylidene chloride in the rat. 1977

M J McKenna, and P G Watanabe, and P J Gehring

The metabolism of inhaled vinylidene chloride in rats represents a balance of biotransformation pathways leading to the formation of a reactive alkylating species which is normally detoxified by conjugation with glutathione. Detoxification of the reactive intermediate formed from inhaled VDC is dependent upon the availability of hepatic glutathione (GSH); as VDC exposure concentrations are increased, the fraction of the dose detoxified by conjugation with GSH decreases markedly, commensurate with depletion of hepatic GSH. This reactive intermediate in the absence of GSH alkylates hepatic macromolecules and causes cell death. Similarly, hepatic GSH plays a vital role in the detoxification of the reactive metabolite formed from inhaled vinyl chloride (VC). However, the dose--response relationships for the utilization of GSH and the accumulation of alkylating metabolites following inhalation exposure to either VDC or VC point to distinct differences which may explain the differing biological activities of the two materials. Finally, preliminary pharmacokinetic data for inhaled VDC in mice indicate an enhanced susceptibility to VDC by virtue of an increased ability for production of alkylating VDC metabolites over that observed in the rat. The importance of these findings in light of recent evidence for a carcinogenic effect of VDC in mice is discussed.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D009374	Neoplasms, Experimental	Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.	Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
D004000	Dichloroethylenes	Toxic chlorinated unsaturated hydrocarbons. Include both the 1,1- and 1,2-dichloro isomers. Both isomers are toxic, but 1,1-dichloroethylene is the more potent CNS depressant and hepatotoxin. It is used in the manufacture of thermoplastic polymers.	Vinylidene Chlorides,Chlorides, Vinylidene
D004781	Environmental Exposure	The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals.	Exposure, Environmental,Environmental Exposures,Exposures, Environmental
D005978	Glutathione	A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.	Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D006843	Hydrocarbons, Chlorinated	Hydrocarbon compounds with one or more of the hydrogens replaced by CHLORINE.	Chlorinated Hydrocarbon,Chlorinated Hydrocarbons,Organochlorine Compound,Chlorine Compounds, Organic,Organochlorine Compounds,Compound, Organochlorine,Compounds, Organic Chlorine,Compounds, Organochlorine,Hydrocarbon, Chlorinated,Organic Chlorine Compounds
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001711	Biotransformation	The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
D014752	Vinyl Chloride	A gas that has been used as an aerosol propellant and is the starting material for polyvinyl resins. Toxicity studies have shown various adverse effects, particularly the occurrence of liver neoplasms.	Chloroethylene,Chloride, Vinyl
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus