Daniel F B, Robinson M, Stober J A, Olson G R, Page N P
U.S. Environmental Protection Agency, Cincinnati, Ohio.
J Toxicol Environ Health. 1993 Jul;39(3):383-93. doi: 10.1080/15287399309531759.
1,1,1-Trichloro-2-propanone (1,1,1-TCP) has been identified as a chlorination by-product in finished drinking water supplies. Since little was known of its oral toxicity, exposure studies were conducted with male and female Sprague-Dawley rats (10 males and 10 females/group) exposed by corn oil gavage at 0, 16, 48, 161, or 483 mg/kg for 10 d or 0, 30, 90, or 270 mg/kg for 90 d. Evaluations included mortality, clinical signs, body weight, food consumption, ophthalmology, hematology, clinical chemistry, urinalysis, organ weights, gross pathology, and histopathology. In the 10-d study, severe toxicity was observed at the highest dose level, since most treated animals (8/10 males and 7/10 females) died. Toxicity was also noted at 161 and 48 mg/kg. At 161 mg/kg, 2 males died and an increase in liver weights in both sexes was observed. Acanthosis and hyperkeratosis of the forestomach was present in males and females at 48 mg/kg and above. In the 90-d study, toxicity was significant at 270 mg/kg, with acanthosis and hyperkeratosis of the forestomach evident in most animals and ataxia in about one-half of them. Retinal degeneration, increased serum potassium, and increased blood urea nitrogen were present in females and increased blood calcium in males at that same dose level. Acanthosis and hyperkeratosis were observed in both sexes, and retinal degeneration was prominent in 2 females at 90 mg/kg. It was concluded that 16 mg/kg was the NOAEL (no observed adverse effect level) for the 10-d study while 30 mg/kg was the NOAEL for the 90-d exposure of Sprague-Dawley rats to 1,1,1,-trichloro-2-propanone.
1,1,1-三氯-2-丙酮（1,1,1-TCP）已被确认为成品饮用水供应中的一种氯化副产物。由于对其口服毒性了解甚少，因此开展了暴露研究，用玉米油灌胃法对雄性和雌性斯普拉格-道利大鼠（每组10只雄性和10只雌性）进行暴露实验，剂量分别为0、16、48、161或483毫克/千克，持续10天；或剂量为0、30、90或270毫克/千克，持续90天。评估内容包括死亡率、临床症状、体重、食物摄入量、眼科检查、血液学、临床化学、尿液分析、器官重量、大体病理学和组织病理学。在为期10天的研究中，在最高剂量水平观察到严重毒性，因为大多数受试动物（8/10雄性和7/10雌性）死亡。在161和48毫克/千克剂量时也注意到毒性。在161毫克/千克时，2只雄性死亡，且观察到两性肝脏重量增加。在48毫克/千克及以上剂量时，雄性和雌性大鼠的前胃均出现棘皮症和角化过度。在为期90天的研究中，在270毫克/千克剂量时毒性显著，大多数动物出现前胃棘皮症和角化过度，约一半动物出现共济失调。在同一剂量水平，雌性出现视网膜变性、血清钾升高和血尿素氮升高，雄性出现血钙升高。在两性中均观察到棘皮症和角化过度，在90毫克/千克剂量时，2只雌性出现明显的视网膜变性。研究得出结论，对于为期10天的研究，16毫克/千克是无观察到不良作用水平（NOAEL）；对于斯普拉格-道利大鼠90天暴露于1,1,1-三氯-2-丙酮的情况，30毫克/千克是NOAEL。
