A 52-Week Repeated Dose Toxicity Study of Ultraviolet Absorber 2-(2′-Hydroxy-3′,5′-di-tert-butylphenyl)benzotriazole in Rats

• Published in: Drug and chemical toxicology (New York, N.Y. 1978) N.Y. 1978), 2008, Vol.31 (1), p.81-96
• Main Authors: Hirata-Koizumi, Mutsuko, Ogata, Hidehiro, Imai, Toshio, Hirose, Akihiko, Kamata, Eiichi, Ema, Makoto
• Format: Article
• Language: English
• Subjects: Administration, Oral; Alkaline Phosphatase - blood; Animals; Benzotriazole UV absorber; Biological and medical sciences; Blood Glucose - drug effects; Body Weight - drug effects; Chemical and industrial products toxicology. Toxic occupational diseases; Chronic toxicity; Dose-Response Relationship, Drug; Erythrocytes - drug effects; Female; Gender-related difference; Heart - drug effects; Liver - drug effects; Liver - pathology; Male; Medical sciences; No-Observed-Adverse-Effect Level; Organ Size; Radiation-Protective Agents - administration & dosage; Radiation-Protective Agents - toxicity; Rat; Rats; Rats, Sprague-Dawley; Sex Factors; Time Factors; Toxicity Tests, Chronic; Toxicology; Triazoles - administration & dosage; Triazoles - toxicity; Ultraviolet Rays; Various organic compounds
• ISSN: 0148-0545; 1525-6014
• DOI: 10.1080/01480540701688758

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.