Consideration of carcinogenicity and mode of action information by an independent expert panel to support derivation of no-significant-risk-level values for vinyl acetate monomer.

A triple-blinded, independent panel of five experts was engaged to review information on the cancer mode of action (MOA) of vinyl acetate monomer (VAM) to provide input on key decisions for the calculation of No-Significant-Risk-Level (NSRL) values using best available science. Based upon the weight of evidence, the panel expressed a strong preference for using effects observed at the point of contact for the NSRL rather than in using those observed in systemic tissues. None of the systemic endpoints were identified as useful for quantitative risk assessment. A cancer MOA involving cytotoxicity and regenerative cell proliferation was best supported by the weight of evidence (mean score of +3.8 ± 1.1; scale of -5 to +5). In contrast, a cancer MOA involving direct genotoxicity was not supported for VAM (mean score of -3.6 ± 2.1). Separate NSRL values were derived for inhalation and oral routes. Based upon the decisions recommended by the panel at each step of the process, inhalation and oral NSRL values of 20,000 and 110,000 μg/day were calculated, respectively. Confidence in the inhalation and oral NSRL values was considered high and medium, respectively by the panel. Human exposures at or below these NSRL levels are not expected to pose a significant cancer risk.