Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 5 No. 1 January 19, 2018 p.1-11
Original Article
A 28-day repeated oral-dose toxicity study of insecticide synergist N-(2-ethylhexyl)-1-isopropyl-4-methylbicyclo[2.2.2] oct-5-ene-2,3-dicarboximide in rats
  • Mariko Matsumoto (Division of Risk Assessment, Biological Safety Research Center, National Institute of Health Sciences / mariko@nihs.go.jp)
Mariko Matsumoto 1) , Masatoshi Furukawa 2) , Katsumi Kobayashi 1) , Takako Iso 1) , Toshime Igarashi 1) , Takashi Yamada 1) , Akihiko Hirose 1)
1) Division of Risk Assessment, Biological Safety Research Center, National Institute of Health Sciences , 2) Safety Research Division, Safety Research Institute for Chemical Compounds Co., Ltd.
Keywords: CAS No. 13358-11-7, Synepirin 500, Synergist, OECD TG 407, Repeated dose toxicity
Abstracts

N-(2-Ethylhexyl)-1-isopropyl-4-methylbicyclo[2.2.2]oct-5-ene-2,3-dicarboximide (Synepirin 500; CAS: 13358-11-7) is used as a synergist, a chemical that makes pesticide ingredients more effective. People can be exposed to Synepirin 500 by using insecticides containing this chemical or from residues in food. The Japanese government chose this chemical as a target substance in its existing chemical testing program. Crl:CD(SD) rats were administered 0, 40, 200, and 1000 mg/kg/day Synepirin 500 by gavage for 28 days, followed by a 14 day recovery period. Diarrhea or soft feces were observed in both sexes at 1000 mg/kg/day. Absolute and/or relative liver weights significantly increased at ≥ 40 mg/kg/day in females and at ≥ 200 mg/kg/day in males. Absolute and/or relative thyroid weights significantly increased in both sexes at 1000 mg/kg/day. These changes were still significant at the end of the recovery period in females. Significantly prolonged prothrombin time and activated partial thromboplastin time were observed in males receiving ≥ 40 mg/kg/day. Histopathological changes in the liver and thyroid were observed in both sexes at 1000 mg/kg/day. On the basis of the effects on the liver, the level of the lowest observed adverse effect from repeated doses of Synepirin 500 was judged to be 40 mg/kg/day for rats.