A 52-week repeated dose toxicity study of ultraviolet absorber 2-(2'-hydroxy-3',5'-di-tert-butylphenyl)benzotriazole in rats.

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.