Inhalation Carcinogenicity of Epichlorohydrin in Noninbred Sprague-Dawley Rats

Abstract

Inhalation exposure experiments with the direct-acting alkylating agent epichlorohydrin (ECH) were done on noninbred male Sprague-Dawley rats. Single 6-hour exposure to ECH and follow-up for 14 days showed the median lethal concentration to be about 360 ppm. Further inhalation experiments were done with 6-hour exposures 5 days/week. A short-term 30-exposure regimen with 100 ppm ECH produced malignant squamous cell carcinomas of the nasal cavity in 15 of 140 rats and respiratory tract papillomas in 3 rats. Among 100 rats, lifetime exposure to 30 ppm yielded 1 malignant squamous carcinoma of the nasal cavity plus 1 nasal papilloma. No nasal or respiratory tract tumors were produced by lifetime exposure of 100 rats to 10 ppm. As controls, 100 air-treated and 50 untreated rats were used. A dose-rate effect was observed for ECH inasmuch as 30-day exposures to 100 ppm (3,000 ppm-days) produced 15 cancers in comparison to the 1 cancer from the lifetime exposures to 30 ppm (8,700 ppm-days) and no cancers from lifetime exposure to 10 ppm (2,500 ppm-days).