Carcinogenicity of vinyl acetate: evidence from multiple data streams.

backgroundVinyl acetate (VA) is a synthetic chemical that can be metabolized to form the carcinogen acetaldehyde (AA). This paper summarizes the key evidence relevant to the evaluation of VA’s carcinogenicity.

methodsWe conducted a literature search and reviewed data relevant to the carcinogenicity of VA using a systematic approach. The literature reviewed included epidemiological studies, animal carcinogenicity studies, pharmacokinetic and metabolism studies, as well as studies relevant to the key characteristics of carcinogens.

resultsThe body of epidemiological evidence includes several occupational studies with significant limitations and one prospective cohort study that assessed ambient air exposure to VA and breast cancer risk. The evidence from animal carcinogenicity studies is considered strong. VA induced tumors in a number of tissues across different strains of rats and mice in both sexes, via two exposure routes (inhalation and drinking water). Some tumor findings showed dose-related trends and were not limited to site-of-entry tissues. VA’s metabolic link to AA strengthens the evidence by providing biological plausibility: both chemicals induced many of the same DNA adducts, genotoxicity endpoints, and tumor types at many of the same sites. In addition, VA demonstrates three of the ten key characteristics of carcinogens in that it can be metabolically activated to be electrophilic, is genotoxic, and induces cell proliferation.

conclusionOur review of VA’s carcinogenicity shows compelling evidence in animal cancer bioassays with supporting mechanistic data, including the formation of reactive compounds and DNA adducts, evidence of genotoxicity including clastogenicity and DNA damage, and the ability to induce cell proliferation and pre-neoplastic lesions. The metabolic link to AA was an important consideration.