Gender-Related Difference in the Toxicity of 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 absorber. Previously, we showed that male rats had more than a 100 times higher susceptibility to the toxic effects of DBHCB than females. In order to investigate the role of sex steroids in the mediation of this gender-related difference, DBHCB (0 or 250 mg/kg/day) was given to male and female young intact and castrated rats by gavage for 28 days in the current study. In intact rats, relative liver weight increased to more than two times that of the control in males, while the rate of change was less than 10% in females. On histopathology, hypertrophy of hepatocytes was observed in males but not in females. In castrated rats, an approximately 40% increase in the relative liver weight was found only in males, and no histopathological changes in the liver were detected in either sex. The gender-related difference was also determined in preweaning rats administered DBHCB at 0, 250, or 500 mg/kg/day by gavage from postnatal days 4 to 21. Blood biochemical changes, including increases in the levels of AST, ALT, and ALP, 80–95% increase in the relative liver weight and histopathological changes in the liver, such as hypertrophy and single cell necrosis of hepatocytes, were observed at both doses in both sexes. In conclusion, the gender-related difference in the toxicity of DBHCB, which was observed in young rats, was markedly reduced by castration and abolished in preweaning rats.