Weight-of-the-evidence review of acrylonitrile reproductive and developmental toxicity studies

Risk assessment of acrylonitrile (AN) toxicity to humans has focused on potential carcinogenicity and acute toxicity. Epidemiological studies from China reported reproductive and developmental effects in AN workers, including infertility, birth defects, and spontaneous abortions. A weight-of-the-evidence (WoE) evaluation of the AN database assessed study strength, characterized toxicity, and identified no-observed-adverse-effect levels (NOAELs). The epidemiological studies do not demonstrate causality and are not sufficiently robust to be used for risk assessment. Rodent developmental studies showed fetotoxicity and malformations at maternally toxic levels; there was no unique developmental susceptibility. NOAELs for oral and inhalation exposures were 10 mg/kg/day and 12 ppm (6 h/day), respectively. Drinking-water and inhalation reproductive toxicity studies showed no clear effects on reproductive performance or fertility. Maternally toxic concentrations caused decreased pup growth. The drinking-water reproductive NOAEL was 100 ppm (moderate confidence due to study limitations). The inhalation exposure reproductive and neonatal toxicity high confidence NOAEL was 45 ppm (first generation 90 ppm) (6 h/day). The inhalation reproductive toxicity study provides the most robust data for risk assessment. Based on the WoE evaluation, AN is not expected to be a developmental or reproductive toxicant in the absence of significant maternal toxicity.