Repeated-Dose and Reproductive Toxicity of the Ultraviolet Absorber 2-(3′,5′-Di-tert-butyl-2′-hydroxyphenyl)-5-chlorobenzotriazole in Rats

Abstract

2-(3′,5′-Di-tert-butyl-2′-hydroxyphenyl)-5-chlorobenzotriazole (DBHCB) is widely used as an ultraviolet (UV) absorber. In this study, the repeated dose and reproductive toxicity of DBHCB was evaluated in rats. Crj:CD(SD)IGS rats were given DBHCB by gavage at 0, 2.5, 25, or 250 mg/kg/d. Male and female rats were dosed beginning 28 d before mating, and each female rat was mated with a male rat of the same dosage group. Males were dosed for a total of 56–57 d, and females were dosed for a total of 55–69 d up to Day 3 of lactation throughout the mating and pregnancy periods. Ten males from each group were killed on the next day of the last administration, and 10 females were killed on Days 4–6 after parturition. Five rats/sex treated at 0 and 250 mg/kg/d for 56 d were then kept without treatment for 14 d (recovery period). No deaths were found in any group. No effects of DBHCB on general condition, body weight, food consumption, or reproductive/developmental parameters were observed. Significant increases in serum albumin and an albumin/globulin ratio at 25 mg/kg/d and higher and alkaline phosphatase levels at 250 mg/kg/d were noted in males. The absolute and relative weights of the liver were significantly increased in males at 25 mg/kg/d and higher. Significantly increased serum albumin and absolute and relative liver weight were also found in males at 250 mg/kg/d after the recovery period. No changes in these parameters were observed in females of any DBHCB-treated groups. No significant changes in organ histopathology were found in males or females. These findings indicated a sex difference in the toxicity of DBHCB in rats.

Key Words: :

• Repeated-dose toxicity
• Reproductive and developmental toxicity
• UVabsorber
• Benzotriazole
• Rat.

Notes

OECD (Organization for Economic Co-operation and Development) 1996 OECD Guideline for the Testing of Chemicals, 422. Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test.