Hurt S S, Smith J M, Hayes A W
Toxicology. 1983 Dec;29(1-2):1-37. doi: 10.1016/0300-483x(83)90036-7.
With the exception of occasional reports of skin irritation, 20 years of commercial nitrofen use has not produced indications of toxicity in man. In mature non-pregnant laboratory animals nitrofen is only slightly toxic after acute oral, dermal, or respiratory exposures, and it is not a sensitizer. However, absorption through skin occurs rapidly from solvent-based formulations. Chronic administration in the diet at doses of 20 mg/kg body wt/day and higher produced liver toxicity in mice, rats, and dogs with liver tumors developing in mice at dose levels at 470 mg/kg/day. In addition to liver tumors in mice, the National Cancer Institute's Carcinogen Bioassay Program also found a dose-related incidence of pancreatic tumors in females of 1 of 2 strains of rat after lifetime feeding at levels at and above 65 mg/kg/day. Single and repeated doses given during pregnancy to rats and mice produce neonatal lethality accompanied by signs of impaired breathing, diaphragmatic hernias, heart anomalies, hydronephrosis, and apparent eye anomalies which are due to effects on the Harderian gland. These anomalies were produced by both oral and dermal doses, but did not occur in the rabbit or when dosing was restricted to the male parent only. Neonatal deaths appear after repeated maternal doses of 3 mg/kg/day and higher; the overall no observed effect level for effects in the offspring was 0.17 mg/kg/day. Based on a 10(-6) level of tumorigenic risk the acceptable average daily intake for man is 1 microgram/kg/day; pregnant women should not be exposed to more than 1.7 micrograms/kg in any single 24-h period.
除了偶尔有皮肤刺激的报告外，20年的商业使用中，除草醚未显示对人类有毒性迹象。在成年未孕实验动物中，除草醚经急性口服、皮肤或呼吸道接触后仅有轻微毒性，且无致敏性。然而，基于溶剂的制剂可迅速经皮肤吸收。以20毫克/千克体重/天及更高剂量长期经饮食给予小鼠、大鼠和狗，可导致肝脏毒性，小鼠在剂量达到470毫克/千克/天时会出现肝肿瘤。除小鼠肝肿瘤外，美国国家癌症研究所的致癌物生物测定项目还发现，两种品系大鼠中的一种雌性大鼠在以65毫克/千克/天及以上剂量终身喂食后，胰腺肿瘤的发生率与剂量相关。在大鼠和小鼠孕期给予单次和重复剂量可导致新生仔畜死亡，并伴有呼吸受损、膈疝、心脏畸形、肾积水和明显的眼部畸形等体征，这些是由于对视腺的影响所致。口服和皮肤给药均会导致这些畸形，但在兔子中未出现，或仅对雄性亲本给药时也未出现。母体重复剂量达到3毫克/千克/天及以上时会出现新生仔畜死亡；对后代无影响的总体未观察到效应水平为0.17毫克/千克/天。基于致癌风险水平为10(-6)，人类可接受的平均每日摄入量为1微克/千克/天；孕妇在任何24小时期间接触量不应超过1.7微克/千克。
