Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Vinyl chloride has tested positive in a number of in vitro and in vivo mutagenicity studies, DNA damage and cytogenicity assays.

Regarding in vitro data, the key Ames study gave positive results in the absence and presence of metabolic activation. The key in vitro gene mutation test was negative in absence of metabolic activation but positive with metabolic activation.

An in vivo micronucleus assay in mice was found positive and a dominant lethal assay in mice was negative. It has been suggested that negative results in the latter test could be attributed to the inability of vinyl chloride or its active metabolites to reach germ cells in sufficient amounts to induce mutation. An in vivo chromosome aberration assay in rats was negative while two cytogenetic assays in hamsters were positive.

It is suggested that vinyl chloride is metabolically converted into a short-lived alkylating intermediate which introduces the 2-oxoethyl group onto nucleophilic sites in DNA and proteins. The main reactive metabolite is assumed to be chloroethylene oxide. These metabolites have been shown to produce DNA adducts.

 

Human data shows that chromosomal aberrations in human peripheral lymphocytes of exposed workers have been detected in many studies and breaks appear to be localized in specific chromosomes.

Short description of key information:
Vinyl chloride tested positive in the Ames test. In an in vitro gene mutation test, vinyl chloride was negative in the absence of metabolic activation, but positive with metabolic activation. In mice, an in vivo micronucleus test was positive, but an in vivo dominant lethal assay was negative. An in vivo chromosome aberration assay in rats was negative while two cytogenetic assays in hamsters were positive. Chromosomal aberrations have also been observed in peripheral lymphocytes of exposed workers in some studies.

Endpoint Conclusion: Adverse effect observed (positive)

Justification for classification or non-classification

Vinyl chloride (and/or its metabolites) produces DNA adducts and has been positive in gene mutation and chromosomal aberration assays in vitro and in vivo. Chromosomal aberrations have also been observed in peripheral lymphocytes of exposed workers in some studies. However, vinyl chloride does not induce dominant lethal mutations in mice. It has been suggested that negative results in this test could be attributed to the inability of vinyl chloride or its active metabolites to reach germ cells in sufficient amounts to induce mutation (neither in animals nor in humans). Therefore, vinyl chloride does not induce heritable genetic damage. The substance has been included on Annex I of Directive 67/548/EEC (19th ATP, October 16, 1993) and not classified as mutagenic. Since then, no additional studies on genotoxicity of vinyl chloride, which would encourage reconsidering that classification, became available. Therefore classification is not warranted in accordance with Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.