Abstract
Thenyldiamine was administered as an admixture in the feed to male and female B6C3F, mice for 14 days or for 90 days. Dose levels of 0, 250, 500, 1000, 2000, and 4000 ppm thenyldiamine were administered in both studies. There was little toxicity observed in the 14-day study. Male and female mice in the 4000 ppm dose groups gained less weight in the first week but appeared to recover and weighed essentially the same as controls at the end of the second week. No significant abnormal clinical observations were made during the study and no treatment-related lesions were observed at necropsy. Microscopic lesions were confined to focal necrosis of the liver with associated inflammatory cell infiltration. In the 90-day study, a more pronounced reduction of weight gain was seen in both males and females of the 4000 ppm dose group. Clinical observations were unremarkable. No abnormal lesions were observed at necropsy. Treatment-related microscopic lesions were confined to the liver of males and parotid salivary gland of both sexes. The parotid gland exhibited necrosis of individual acinar cells randomly distributed throughout the gland. Due to the physiological nature of the parotid gland, the toxicological significance of this lesion is questionable. The liver changes were very subtle, although the zone of affected cells was often extensive. The changes consisted of cytomegaly and karyomegaly of the hepatocytes which was centrilobular and diffuse. Whether the subtle changes represent a possible carcinogenic and/or promoting effect will require further studies to resolve. The results indicate an appropriate maximum tolerated dose for a lifetime chronic study would be between 2000 and 4000 ppm thenyldiamine.