Repeated dose and reproductive/developmental toxicity of perfluorooctadecanoic acid in rats

Mutsuko Hirata-Koizumi, Sakiko Fujii, Masatoshi Furukawa, Atsushi Ono, Akihiko Hirose

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Male and female rats were given perfluorooctadecanoic acid (PFOdA) by gavage at 40, 200 or 1,000 mg/kg/day, and each female was mated with a male in the same dose group after 14-day administration. Males were dosed for 42 days and females were dosed throughout the gestation period until day 5 of lactation. One female given 1,000 mg/kg/day was euthanized on day 18 of gestation due to a moribund condition; however, no other treatment-related clinical signs of toxicity were observed. Body weights fell at 1,000 mg/kg/day from day 28 through the administration period in males and throughout gestation and lactation in females. Red blood cell count, hemoglobin level and hematocrit were decreased at 200 and 1,000 mg/kg/day in males and activated partial thromboplastin time was prolonged at 1,000 mg/kg/ day in females. Histopathological examination revealed hepatic changes, such as centrilobular hypertrophy and necrosis, in males given 200 and 1,000 mg/kg/day and in females given 1,000 mg/kg/day. Pancreatic zymogen granule was decreased in both sexes at 1,000 mg/kg/day. As for reproductive and developmental toxicity, there were decreases in the number of corpora lutea, implantation, total number of pups born and the number of live pups on postnatal days 0 and 4 at 1,000 mg/kg/day. At this dose, birth weights of pups were decreased and postnatal body weight gain was inhibited. Based on these findings, the NOAEL of PFOdA was considered to be 40 mg/kg/day for repeated dose toxicity and 200 mg/kg/day for reproductive/developmental toxicity.

Original languageEnglish
Pages (from-to)63-79
Number of pages17
JournalJournal of Toxicological Sciences
Volume37
Issue number1
DOIs
Publication statusPublished - Feb 2012
Externally publishedYes

Fingerprint

Toxicity
Rats
Acids
Enzyme Precursors
Lactation
Pregnancy
Thromboplastin
Body Weight
Hemoglobins
Blood
No-Observed-Adverse-Effect Level
Cells
Erythrocyte Count
Partial Thromboplastin Time
Corpus Luteum
Secretory Vesicles
Hematocrit
Birth Weight
Hypertrophy
Weight Gain

Keywords

  • Perfluorooctadecanoic acid
  • Rat
  • Repeated dose toxicity
  • Reproductive and developmental toxicity
  • Screening test

ASJC Scopus subject areas

  • Toxicology

Cite this

Repeated dose and reproductive/developmental toxicity of perfluorooctadecanoic acid in rats. / Hirata-Koizumi, Mutsuko; Fujii, Sakiko; Furukawa, Masatoshi; Ono, Atsushi; Hirose, Akihiko.

In: Journal of Toxicological Sciences, Vol. 37, No. 1, 02.2012, p. 63-79.

Research output: Contribution to journalArticle

Hirata-Koizumi, Mutsuko ; Fujii, Sakiko ; Furukawa, Masatoshi ; Ono, Atsushi ; Hirose, Akihiko. / Repeated dose and reproductive/developmental toxicity of perfluorooctadecanoic acid in rats. In: Journal of Toxicological Sciences. 2012 ; Vol. 37, No. 1. pp. 63-79.
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