Disappearance of gender-related difference in the toxicity of benzotriazole ultraviolet absorber in juvenile rats.

2-(2'-hydroxy-3',5'-di-tert-butylphenyl)benzotriazole (HDBB) is an ultraviolet absorber used in plastic resin products, such as building materials and automobile components. In oral repeated dose toxicity studies using 5- or 6-week-old rats, this chemical induced hepatic histopathological changes, such as hypertrophy accompanied with eosinophilic granular changes and focal necrosis of hepatocytes, and male rats showed nearly 25 times higher susceptibility to the toxic effects than females. Castration at approximately 4 weeks of age markedly reduced the sex-related variation in HDBB toxicity, but some difference, less than five times, remained between male and female castrated rats. Following oral HDBB administration to male and female juvenile rats from postnatal days 4-21, such gender-related difference in toxic susceptibility was not detected; therefore, it is speculated that the determinants of susceptibility to HDBB toxicity are differentiated between sexes after weaning. In young rats given HDBB, there was no gender-related difference in plasma HDBB concentration, and no metabolites were detected in the plasma of either sex. HDBB induced lauric acid 12-hydroxylase activity in the liver and this change was more pronounced in males than in females. These findings indicate that HDBB could show hepatic peroxisome proliferation activity, and the difference in the susceptibility of male and female rats to this effect might lead to marked gender-related differences in toxicity.