Allyl isothiocyanate (AITC) is a naturally occurring fungicide, herbicide, insecticide, bacteriocide, nematicide, and animal repellent. It acts as a chemical irritant and is used as a model inflammatory and nociceptive pain-inducing agent. Risk assessment of AITC was prompted by its proposed registration in California as a fumigant. Acute, subchronic and chronic toxicological studies of AITC were compiled by conducting extensive systematic review of publically available data, and data required for federal and state registration. The dose responses of endpoints were modeled using U.S. EPA’s Benchmark Dose Software (BMDS 3.1.2), and evaluated for use as critical points of departure. Clinical symptoms of exposure to AITC in humans include irritation, lacrymation, and acute pain and inflammation. Toxicokinetic data demonstrates that AITC is readily completely absorbed (&gt;90%) after oral ingestion. It is primarily metabolized via glutathione conjugation in rats and humans and by hydrolysis in mice, and all metabolites are excreted in urine within 24 h. The studies reviewed for this assessment demonstrated that AITC is capable of inducing both portal of entry (including skin irritation and corrosion, nasal epithelial degeneration, and thickened stomach mucosa) and systemic effects. In rats, systemic effects include cataracts, retinopathy, urinary bladder hyperplasia, increased liver weight, glutathione induction, decreased motor activity, and increased thyroid weight. Tumors were observed in rats, but not in mice, with chronic oral exposure. While the results for <i>in vitro</i> and <i>in vivo</i> mutagenicity tests of AITC were largely negative, results reported for several genotoxicity assays, including DNA damage and chromosomal aberrations, were considered to be “weakly positive” or “marginal” by the study authors because they were observed at concentrations that also resulted in cytotoxicity. The systemic effect of urinary bladder hyperplasia appears to be the most sensitive effect in chronic oral exposure studies.

Allyl isothiocyanate (AITC) hazard identification

ACS Fall 2020 Virtual Meeting

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