Charles P. Carpenter

Reproducibility of Single Oral Dose Toxicity Testing

Abstract The single peroral dose toxicity of 26 chemicals was estimated each year for 12 years to determine the reproducibility of the test and of commercial production. For 11 years the resultant median lethal doses were relatively unaffected by the different samples of each chemical received annually, by changes in the stock of rats, by the diluted or undiluted state of the materials, or by the change of personnel performing the tests. Only one variable, the weight of the rat, appeared to have a significant effect on the LD50.

Toxicologic studies on 3,5-dimethyltetrahydro-1,3,5,2H-thiadiazine-2-thione, a soil fungicide and slimicide

Toxicologic studies completed in 1957 on 3,5-dimethyltetrahydro-1,3,5,2H-thiadiazine-2-thione (UCC 974), a soil fungicide and papermaking slimicide are reported. In rats the oral LD50 ranged from 0.32 to 0.62 g/kg. For mice, guinea pigs, and rabbits, the LD50 was 0.18, 0.16, and 0.12 g/kg, respectively. Intraperitoneally the LD50 for rats was 0.087 g/kg, for rabbits 0.127 g/kg, and for dogs approximately 0.05 g/kg. In rats, 2000 ppm in the diet was not lethal in 30 days, although food intake and growth were low and kidneys and livers were heavy in relation to body weight, but normal histopathologically. During two years, 640 ppm did not affect mortality among rats but reduced growth and caused liver and kidney lesions. Even 10 ppm resulted in liver and kidney changes which are interpreted as a response to irritation, not irreversible or progressive injury. The effects in dogs receiving by capsule the equivalent of 45 ppm in the diet for one year were the same in degree as those in rats at 40 ppm in the diet. UCC 974 slowly hydrolyzes inside or outside of the body to form carbon disulfide, formaldehyde, and methylamine. Human patch tests reveal it to be a skin sensitizer.