Studies on the metabolism of vinyl chloride.

Abstract

Vinyl chloride (VCM) is not carcinogenic by itself, it is bioactivated to the highly reactive alkylating oxirane chloroethylene oxide. Further metabolism, apparently, leads via an interaction of the primary alkylating metabolites with glutathion to S-(2-carboxy-methyl)-cysteine and thiodiacetic acid which are eliminated with the urine. Up to now, it has not been ascertained whether the oxirane alone is the essential carcinogenic factor or whether other metabolites are also involved in carcinogenicity. Likewise, it is still unknown whether the metabolites excreted in the urine might be used as biological criteria for exposure to VCM, because these metabolites probably can originate from a series of substances other than VCM. This problem could stimulate investigations on the possible carcinogenic activity of these substances.

Electron microscopic observations of hepatic and subcutaneous hemangiosarcomas induced in mice exposed to vinyl chloride monomer

“…Oncogenicity of vinyl chloride has been explained in terms of metabolism of the chemical in the hepatic microsomes. It has been strongly suggested that vinyl chloride itself is not carcinogenic but rather that metabolites of the chemical, including chloroethylene oxide and chloracetaldehyde, are responsible as the ultimate carcinogens for the induction of the chemical-induced neoplasms [Antweiler, 1976;Hathway, 1977;Berk et al, 19761. Formation of metabolites in the hepatic cell, the discharge of the metabolites into the sinusoidal endothelium and malignant transformation of the cndotheliuni have been suggested as the mechanism of induction of hepatic hemangiosarcomas [Schaffner et al, 19761.…”