How Can Mode-of-Action Analysis Clarify Chemical Cancer Risk?

For pesticide registrants, animal study often form the basis for regulatory risk assessment, but sometimes the results are not relevant for human exposures. Methyl isothiocyanate (MITC), a compound formed in soil following the application of certain fumigants, has long been the subject of toxicological research to better understand its biological effects.

In a new publication in the Journal of Toxicology and Environmental Health, Part B, Exponent's Rick Reiss and coauthors examine the mode of action (MOA) for nasal tumors observed in Sprague Dawley rats exposed to MITC by inhalation.

Drawing on evidence from chronic inhalation studies, the authors conclude that the nasal tumor findings are consistent with a threshold-based, non-genotoxic MOA driven by local tissue irritation and cytotoxicity. They further conclude that MITC tumorigenicity exhibits exposure thresholds and is not likely to pose a carcinogenic risk to humans under normal use patterns and corresponding exposure levels. The U.S. Environmental Protection Agency agreed with this analysis and classified MITC as "Not likely to be carcinogenic to humans below concentrations that induce regenerative proliferation of the nasal cavity epithelium."

The publication demonstrates how MOA analysis can place animal tumor findings in biological context and help distinguish hazard identification from human-relevant risk under expected exposure conditions.

From the publication: "Tumorigenicity of MITC exhibits exposure thresholds but is not likely to pose a carcinogenic risk to humans under normal use pattern."