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

  • Food Chem Toxicol. 2013 Jun:56:290-6. doi: 10.1016/j.fct.2013.02.029.
Mariko Matsumoto  1 ,  Makiko Yamaguchi ,  Yuka Yoshida ,  Mika Senuma ,  Hiromasa Takashima ,  Tomoko Kawamura ,  Hina Kato ,  Mika Takahashi ,  Mutsuko Hirata-Koizumi ,  Atsushi Ono ,  Kazuhito Yokoyama ,  Akihiko Hirose
Affiliations
  • 1. Division of Risk Assessment, Biological Safety Center, National Institute of Health Sciences, Tokyo 158-8501, Japan.
PMID: 23454298 DOI: 10.1016/j.fct.2013.02.029
Abstract

A 28-day repeated dose toxicity test and reproduction/developmental toxicity test for N,N'-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.

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