A toxicologic evaluation of 5-ethoxy-3-trichloromethyl-1,2,4-thiadiazole (ETMT)

Abstract

The following studies were conducted on 3-ethoxy-3-trichloromethyl-1,2,4-thiadiazole (ETMT, Terrazole), a soil fungicide: acute oral toxicity in rats, rabbits, and dogs; acute and subchronic percutaneous toxicity in rabbits; subchronic feeding to rats and dogs; 2-year feeding to rats and dogs; and a three-generation reproduction study in rats. CD rats, albino rabbits, and mongrel and beagle dogs were employed. The acute oral toxicity values (LD 50 ± SD) were: rats, 1077 ± 78 mg/kg; rabbits, 779 ± 532 mg/kg; dogs > 5000 mg/kg (premedicated with morphine). The test material was added to the diet of rats at levels of 0, 78, 156, 312, 625, and 1250 ppm (subchronic study) and 0, 10, 80, and 640 ppm (chronic study and reproductive study); and to the diet of dogs at levels of 0, 100, 400, and 1600 ppm (subchronic study); and 0, 10, 100, and 1000 ppm (chronic study). Three-month feeding in rats resulted only in growth inhibition at 1250 ppm and elevated liver to body weight ratios at 625 and 1250 ppm. Dogs fed 3 months showed a decrease in spleen-to-body weight ratios at all feeding levels and a higher liver-to-body weight ratio at 1600 ppm. No consistent adverse dose-related effects were apparent in the 2-year rat feeding study. The following findings were noted only in dogs that received the 1000-ppm diet: a lesser body weight gain, increases in SAP, SGOT, serum cholinesterase, BSP retention, liver weights; cholestatic hepatosis with secondary bile nephrosis. No adverse effects were apparent at 10 or 100 ppm. In the three-generation reproduction study, no adverse effects were apparent on fertility, gestation, viability, lactation, number of stillborn, and mean number of pups born and weaned per litter. Adverse effects occurred only on the 640-ppm diet and these consisted of lower weaning weights of offspring and depressed body weight gains of parent rats.