Regulatory toxicology and pharmacology : RTP

Dose response assessment for effects of acute exposure to methyl isothiocyanate (MITC).

PMID 20406661


The preplant fumigants, metam-sodium, metam-potassium, and dazomet undergo decomposition to the biocide methyl isothiocyanate (MITC) in moist soils. Since MITC vapor can migrate from its site of application, we developed an estimate of health protective concentrations for airborne exposures to MITC that prevents effects among bystanders near treated agricultural fields. Our findings show that, at concentrations of environmental relevance, MITC most likely acts via stimulation of the trigeminal nerve, which mediates sensory irritation in the eyes and nose. Several lines of evidence support the conclusion that sensory irritation of the eyes is the most sensitive effect relevant for health risk assessment arising from short-term MITC exposures. The outcome of a clinical study that included sensitive individuals and measured multiple ocular responses to irritation (e.g., perceived irritation, tearing, and blinking of the eyes) is consistent with this proposed mode of action, as are experimental animal data. Databases and studies by the California Department of Pesticide Regulation (CDPR) show that, in accidental exposures, human eye irritation is consistently the most sensitive endpoint at low-modeled acute exposure and is often the most sensitive endpoint from acute exposures of unknown, but likely higher, concentrations. Based upon benchmark concentration lower limits from the clinical study and consideration of uncertainties, health protective concentrations of MITC were estimated as 0.2 ppm for 4h of exposure and 0.8 ppm for 14-min of exposure.