title: Gonadal influence on the toxicity of 2-(2'-hydroxy-3',5'-di-tert-butylphenyl) benzotriazole in rats.
abstract: Previously, we showed that susceptibility of male rats to the toxicity of an ultraviolet absorber, 2-(2'-hydroxy-3',5'-di-tert-butylphenyl)benzotriazole (HDBB), was nearly 25 times higher than that of females. In the current study, we investigated the role of sex steroids in the mediation of the gender-related difference using castrated rats. Male and female castrated CD(SD) rats were given HDBB by gavage at 0, 0.5, 2.5, or 12.5 mg/kg/day for 28 days. No deaths, clinical signs of toxicity, or changes in body weight or food consumption were found at any doses. Blood biochemical changes suggestive of hepatic damage, such as increased levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase, were detected at 12.5 mg/kg/day in males. Absolute and relative liver weight increased at 0.5 mg/kg/day and above in males and at 12.5 mg/kg/day in females. In the liver, histopathological changes, such as nucleolar enlargement, increased mitosis, hypertrophy in hepatocytes, and/or focal necrosis were observed at 0.5 mg/kg/day and above in males, and at 2.5 mg/kg/day and above in females. These findings indicate that castration markedly reduced the gender-related differences in toxicity of HDBB in rats.
authors.affiliation: Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Hirata-Koizumi
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuyama
authors.forename: Toshio
authors.initials: T
authors.lastname: Imai
authors.forename: Akihiko
authors.initials: A
authors.lastname: Hirose
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kamata
authors.forename: Makoto
authors.initials: M
authors.lastname: Ema
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009919:Orchiectomy; D009929:Organ Size; D010052:Ovariectomy; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000633:toxicity*; D014466:Ultraviolet Rays
chemical_list: D012739:Gonadal Steroid Hormones; D011837:Radiation-Protective Agents; D014230:Triazoles; C525485:2-(2'-hydroxy-3',5'-di-tert-butylphenyl)benzotriazole