Repeated-dose and reproductive toxicity of the ultraviolet absorber 2-(3',5'-di- tert-butyl-2'-hydroxyphenyl)-5-chlorobenzotriazole in rats.
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.
Ema
Makoto
M
Research Institute of Science for Safety and Sustainability, National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki, Japan. ema_makoto@aist.go.jp
Fukunishi
Katsuhiro
K
Hirose
Akihiko
A
Hirata-Koizumi
Mutsuko
M
Matsumoto
Mariko
M
Kamata
Eiichi
E
D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D012709:Serum Albumin / Q000187:drug effects / Q000378:metabolism; D012712:Serum Globulins / Q000187:drug effects / Q000378:metabolism; D012737:Sex Factors; D013473:Sunscreening Agents / Q000633:toxicity*; D018675:Toxicity Tests; D014230:Triazoles / Q000633:toxicity*
C511878:2-(3',5'-di-tert-butyl-2'-hydroxyphenyl)-5-chlorobenzotriazole; D012709:Serum Albumin; D012712:Serum Globulins; D013473:Sunscreening Agents; D014230:Triazoles; D000469:Alkaline Phosphatase