Daniel F B, Robinson M, Olson G R, Bercz J P, Page N P
Ecological Monitoring Research Division, U.S. Environmental Protection Agency, Cincinnati, Ohio 45268.
Drug Chem Toxicol. 1993;16(3):293-305. doi: 10.3109/01480549309081821.
Groups of 10 male and 10 female Sprague-Dawley rats were administered 1,1-dichloro-2-propanone in corn oil by gavage at 0, 10, 20, 40, or 80 mg/kg/day for 90 consecutive days. Food and water consumption, body and organ weights, organ-to-body weight ratios, hematology, and clinical chemistry parameters were determined. Gross and microscopic pathology examinations also were conducted. No treatment-related mortality was observed during the study; however, liver, forestomach, and kidney toxicity was evident. Liver changes consisted of cytoplasmic alteration, cytomegaly, karyomegaly, and bile duct hyperplasia. These occurred with significance of p < or = 0.05 at or above 10 mg/kg/day in both sexes. The forestomach lesions included hyperkeratosis and epithelial hyperplasia in both sexes at 40 and 80 mg/kg/day, and ulcerations at 80 mg/kg/day. Also, an increased incidence and severity of spontaneously occurring chronic progressive nephropathy was most apparent in high dose males. Increases in organ-to-body weight ratios were noted for the liver and kidneys in females at the highest dose level and in males at the two highest dose levels. Serum enzymes (ALT, AST, and LDH) were increased in females and decreased in males. Based on liver lesions and biochemical changes, it was concluded that there was no experimentally definable NOAEL.
将10只雄性和10只雌性斯普拉格-道利大鼠分为几组，连续90天每天经口灌胃给予玉米油中的1,1-二氯-2-丙酮，剂量分别为0、10、20、40或80毫克/千克/天。测定食物和水的消耗量、体重和器官重量、器官与体重比、血液学和临床化学参数。还进行了大体和显微镜病理学检查。研究期间未观察到与治疗相关的死亡；然而，肝脏、前胃和肾脏毒性明显。肝脏变化包括细胞质改变、细胞肿大、核肿大和胆管增生。两性在10毫克/千克/天及以上剂量时出现这些变化，p值≤0.05，具有显著性。前胃病变包括40和80毫克/千克/天剂量组两性的角化过度和上皮增生，80毫克/千克/天剂量组出现溃疡。此外，高剂量雄性大鼠自发发生的慢性进行性肾病的发病率和严重程度增加最为明显。最高剂量水平的雌性大鼠以及两个最高剂量水平的雄性大鼠的肝脏和肾脏的器官与体重比增加。雌性大鼠血清酶（ALT、AST和LDH）升高，雄性大鼠血清酶降低。基于肝脏病变和生化变化，得出结论：不存在实验可确定的无观察到有害作用水平（NOAEL）。
