An antioxidant, N,N¡ä-diphenyl-p-phenylenediamine (DPPD), affects labor and delivery in rats: A 28-day repeated dose test and reproduction/developmental toxicity test

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• 作者：Mariko Matsumoto^a ; ^d ; Makiko Yamaguchi^b ; Yuka Yoshida^c ; Mika Senuma^c ; Hiromasa Takashima^c ; ¹ ; Tomoko Kawamura^a ; Hina Kato^a ; Mika Takahashi^a ; Mutsuko Hirata-Koizumi^a ; Atsushi Ono^a ; Kazuhito Yokoyama^d ; Akihiko Hirose^a ; ^{hirose@nihs.go.jp}
• 关键词：ADME ; absorption ; distribution ; metabolism ; and excretion ; COX ; cyclooxygenase ; DPPD ; N ; N&prime ; -diphenyl-p-phenylenediamine ; HPV ; high production volume ; NSAID ; non-steroidal anti-inflammatory drug ; OECD ; Organisation for Economic Co-operation and Develo
• 刊名：Food and Chemical Toxicology
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：56
• 期：Complete
• 页码：290-296
• 全文大小：233 K

文摘

A 28-day repeated dose toxicity test and reproduction/developmental toxicity test for N,N¡ä-diphenyl-p-phenylenediamine (DPPD) were conducted in [Crl:CD(SD)] SPF rats. Male and female rats were dosed with DPPD by gavage for 28 days at 0, 100, 300, or 1000 mg/kg bw/day or for a total of 42-46 days at 0, 8, 50, or 300 mg/kg bw/day. No significant adverse effects were observed in the repeated dose toxicity study up to 1000 mg/kg bw/day in both sexes. In the reproduction/developmental toxicity study, two females showed piloerection, hypothermia, and pale skin; one died and the other showed dystocia on day 23 of pregnancy at 300 mg/kg bw/day. Another female delivered only three live pups at 300 mg/kg bw/day. A significantly prolonged gestation period was observed at 50 and 300 mg/kg bw/day. The NOAELs of repeated dose toxicity and reproduction/developmental toxicity were considered to be 1000 and 8 mg/kg bw/day, respectively.