title: [Twenty-eight day repeated dose oral toxicity test of synergist of a pyrethroid insecticide, 2,3,3,3,2',3',3',3'-Octachlorodipropyl ether (S-421) in rats].
abstract: 2,3,3,3,2',3',3',3'-Octachlorodipropyl ether (Abbreviation; S-421) is originally developed as synergist of a pyrethroid insecticide. In recent years, S-421 is used widely at home, for a mosquito-repellent incense, electric mosquito-repellent, an insect-killing spray, a vacuum cleaner paper pack, etc. as well. On the other hand, S-421 has been detected in vacuum cleaner dust samples as well as human milk samples in Japan indicating that our living environment is already contaminated by this compound. Long term toxicity studies including a carcinogenesis study have been performed and NOEL of chronic toxicity has been settled. However, it is clear that S-421 is used in close proximity so that acute or subacute exposure at relatively higher dose levels than chronic NOEL values are easily assumed, such as use of a spray in an ill-ventilated room, etc. This study, 28 day repeated oral dose toxicity study of S-421 was performed to monitor the outcome of acute and subacute exposure assuming possible exposure accidents mentioned above. The protocol is as follows; Groups of 10 rats of each sex(5 week-old), were treated with intragastric administration of S-421 with a dose of 0 (olive oil, control), 10, 40, 160 or 640 mg/kg body weight. For recovery test, 14 day after the last treatment, the control and 640 mg/kg groups were examined, respectively. All animals of all groups in both sexes survived. In the 640 mg/kg groups of the both sexes, all animals were set to drowsiness from about 5 hours after administration, however, they recovered by the next morning. In the hematology examination, Hb, MCH, MCHC, WBC values were significantly decreased and MCV value was significant increased in the 640 mg/kg group of both sexes. In the serum biochemistry, items increased in the 640 mg/kg groups of both sexes returned to normal level after 14 days recovery period. Absolute and relative liver weight increase seen in the 160 mg/kg and above also returned to control level after recovery. Histopathologically, slight hepatocellular swelling was observed in the 160 mg/kg groups and severe hepatocellular swelling with vacuolization and slight necrosis was seen in the 640 mg/kg group. In conclusion, the no-observed-effect levels (NOEL) of S-421 under these conditions was judged to be 40 mg/kg/day.
authors.affiliation: Division of Cellular & Molecular Toxicology, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya, Tokyo 158-8501, Japan. matsushi@nihs.go.jp
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsushima
authors.forename: Osayuki
authors.initials: O
authors.lastname: Uchida
authors.forename: Minoru
authors.initials: M
authors.lastname: Saitoh
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Isama
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kaniwa
authors.forename: Tohru
authors.initials: T
authors.lastname: Inoue
authors.forename: Jun
authors.initials: J
authors.lastname: Kanno
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001773:Blood Cells / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004987:Ethers / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D006984:Hypertrophy; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009336:Necrosis; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D023382:Toxicity Tests, Acute / Q000379:methods
chemical_list: D004987:Ethers; D007306:Insecticides; C017970:bis(2,3,3,3-tetrachloropropyl) ether