A 52-week repeated dose toxicity study of an ultraviolet absorber, 2-(2'-hydroxy-3',5' -di-tert-butylphenyl)benzotriazole (HDBB), was conducted according to OECD TG 452 under GLP. CD(SD)IGS rats were given HDBB by gavage at 0, 0.1, 0.5, or 2.5 mg/kg/day in males and 0, 0.5, 2.5, or 12.5 mg/kg/day in females. No substance-related deaths or clinical signs of toxicity were observed in any group; however, a lowered body weight was found from day 36 to the end of the 52-week administration period at 2.5 mg/kg in males. At the completion of the dosing period, a decrease in red blood cells at 0.5 mg/kg and higher, and in hematocrit at 2.5 mg/kg, was detected in males. Blood biochemical changes, including increases in the levels of alkaline phosphatase and glucose and the A/G ratio, were also found at 0.5 mg/kg and higher in males and at 12.5 mg/kg in females. At necropsy, absolute and relative liver weight was increased at 0.5 mg/kg and higher in males and at 12.5 mg/kg in females. Histopathological changes were observed in the liver; centrilobular hypertrophy of hepatocytes at 0.5 mg/kg and higher in males, and at 12.5 mg/kg in females, and altered hepatocellular foci at 0.5 mg/kg and higher, and cystic degeneration and lipofuscin deposition in hepatocytes at 2.5 mg/kg in males. Based on these findings, the no observed adverse effect level was concluded to be 0.1 mg/kg/day in male rats and 2.5 mg/kg/day in female rats.

The toxicity of oral 2,4,6-trinitrophenol (TNP) was determined in newborn rats, and compared with that in young rats. In newborn rats, males and females were given TNP at 0, 16.3, 81.4 or 407 mg/kg per day on postnatal days (PND) 4-17 for the dose-finding study, and at 0, 4.1, 16.3 or 65.1 mg/kg per day on PND 4-21 for the main study. Deaths, lower body weight (BW) and behavioral changes were found at 81.4 and 407 mg/kg per day in the dose-finding study, and lower BW was observed in males at 65.1 mg/kg per day during the dosing period of the main study. In young rats, 5-week-old males and females were given TNP at 0, 20, 100 or 500 mg/kg per day for 14 days as the dose-finding study and at 0, 4, 20 or 100 mg/kg per day for 28 days as the main study. Deaths were observed at 500 mg/kg per day in the dose-finding study. Deaths or changes in BW were not found at 100 mg/kg per day or less. At 100 mg/kg per day, hemolytic anemia and testicular toxicity were found. In conclusion, toxicity profiles induced by TNP were markedly different between newborn and young rats.

-Newborn rat studies were conducted with oral administration of 1,3-dibromopropane (DBP) and 1,1,2,2-tetrabromoethane (TBE) from postnatal Days 4 to 21 to allow comparison of NOAELs and unequivocally toxic levels with those from 28-day young rat studies starting at 5-6 weeks of age. The unequivocally toxic level was estimated by our specified criteria, requiring simultaneous change of organ weights, histopathology, some biochemical parameters and body weights, because in this study only hypertrophy of hepatocytes was observed as a major histopathological change. DBP caused centrilobular hypertrophy of hepatocytes with alteration in biochemical parameters, as well as lowering of body weights, regardless of sex, in both newborn and young rats. NOAELs and unequivocally toxic levels were considered to be 50 and 150 mg/kg/day in newborn rats and 10 and 250 mg/kg/day in young rats, respectively. In the newborn rat study of TBE, some hepatic effects observed at the top dose of 50 mg/kg were not considered adverse because of the lack of histopathological changes. Significant lowering of body weight was noted at 200 mg/kg in the dose-finding study but histopathological data were not available. In the young rat study, there was no definite toxicity at 6 mg/kg and hypertrophic changes in liver and thyroids without body weight change occurred at 200 mg/kg. There were no clear sex differences in both the newborn and young rat studies. NOAELs were considered to be 50 and 6 mg/kg/day in newborn and young rats, respectively, but unequivocally toxic levels for both rats could not be estimated. Abnormalities of external and sexual development and reflex ontogeny in the newborn were not observed with either chemical. Based on these results, it can be concluded that the target organ of DBP and TBE is the liver in both newborn and young rats, and that while the doses at which toxic signs began to appear are higher in newborn rats, those causing clear toxicity may be paradoxically lower in the newborn case.