Matsushima Yuko, Uchida Osayuki, Saitoh Minoru, Kawasaki Yasushi, Isama Kazuo, Kaniwa Masaaki, Inoue Tohru, Kanno Jun
Division of Cellular & Molecular Toxicology, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya, Tokyo 158-8501, Japan.
Kokuritsu Iyakuhin Shokuhin Eisei Kenkyusho Hokoku. 2003(121):40-7.
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.
2,3,3,3,2',3',3',3'-八氯二丙醚（缩写：S-421）最初是作为拟除虫菊酯类杀虫剂的增效剂开发的。近年来，S-421在国内被广泛使用，也用于蚊香、电蚊香、杀虫喷雾、吸尘器纸袋等产品中。另一方面，在日本的吸尘器灰尘样本以及人乳样本中都检测到了S-421，这表明我们的生活环境已经受到这种化合物的污染。已经进行了包括致癌性研究在内的长期毒性研究，并确定了慢性毒性的无观察到有害作用水平（NOEL）。然而，很明显S-421的使用非常普遍，因此很容易设想会出现急性或亚急性暴露，其剂量水平相对高于慢性NOEL值，例如在通风不良的房间使用喷雾等情况。本研究进行了S-421的28天重复口服剂量毒性研究，以监测上述可能的暴露事故导致的急性和亚急性暴露的结果。实验方案如下：每组10只各性别（5周龄）的大鼠，通过灌胃给予剂量为0（橄榄油，对照）、10、40、160或640mg/kg体重的S-421。对于恢复试验，在最后一次给药后14天，分别对对照组和640mg/kg组进行检查。所有组的所有动物均存活。在640mg/kg组的两性动物中，所有动物在给药后约5小时开始出现嗜睡，但到第二天早上恢复。血液学检查中，640mg/kg组两性动物的血红蛋白（Hb）、平均红细胞血红蛋白含量（MCH）、平均红细胞血红蛋白浓度（MCHC）、白细胞（WBC）值显著降低，平均红细胞体积（MCV）值显著升高。血清生化检查中，640mg/kg组两性动物升高的指标在14天恢复期后恢复到正常水平。160mg/kg及以上剂量组出现的肝脏绝对重量和相对重量增加在恢复后也恢复到对照水平。组织病理学检查中，160mg/kg组观察到轻度肝细胞肿胀，640mg/kg组观察到严重的肝细胞肿胀伴空泡化和轻度坏死。总之，在这些条件下S-421的无观察到有害作用水平（NOEL）被判定为40mg/kg/天。
