Oncogenicity study of trifluralin in B6C3F1 mice.
Oncogenicity study of trifluralin in B6C3F1 mice.
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B6C3F1 小鼠中氟乐灵的致癌性研究。
DOI：
10.1016/0278-6915(91)90047-b
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
N. Owen
中科院分区：
文献类型：
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作者：
P. Francis;J. L. Emmerson;E. Adams;N. Owen
B6C3F1小鼠以含0.563、2250或4500ppm氟乐灵的饲料饲养24个月。这些饮食浓度分别相当于每天约70、285或570毫克/公斤体重的剂量。对照组为120只/雌鼠，治疗组为80只/雌鼠。对小鼠的存活、外观或行为没有治疗相关的影响。在试验终止时，每组患者的存活率至少为67%。与对照组相比，给予2250和4500 ppm饮食的两性小鼠的平均体重都以与剂量相关的方式显著减轻。在21个月时，体重分别减少了⩾15和⩾30%。在研究结束时，在2250和4500 ppm的饮食水平下，红细胞和白细胞数值也观察到与剂量相关的下降。在临床化学评价中，氟乐灵剂量为2250和4500ppm时，两性小鼠的血尿素氮水平和碱性磷酸酶活力均显著升高。服用低剂量氟乐灵的女性，血尿素氮也略有增加。在所有处理水平下，男性的丙氨酸氨基转移酶活性都显著增加。虽然所有三个处理组的绝对和相对器官重量的变化与对照组显著不同，但在2250和4500ppm的饮食水平下，男性相对肾脏重量的减少和两性的相对肝脏重量的增加是唯一可以与临床化学值变化相关的变化。除了高剂量组女性进行性肾小球肾炎的发病率和严重程度增加外，没有证据表明任何病理情况与治疗相关。长期饮食服用高剂量氟乐灵并不会增加B6C3F1小鼠的良、恶性肿瘤发病率。
B6C3F1mice were maintained for 24 months on diets containing 0, 563, 2250 or 4500 ppm trifluralin. These dietary concentrations corresponded to daily doses of approximately 70, 285 or 570 mg/kg body weight, respectively. The control group contained 120 mice/sex and treated groups consisted of 80 mice/sex. There were no treatment-related effects on the survival, appearance or behaviour of the mice. Survival at test termination was at least 67% in each group. Compared with controls, mean body weight was significantly reduced in a dose-related manner in mice of both sexes given the 2250 and 4500 ppm diets. At 21 months, the reduction in body weight was ⩾ 15 and ⩾ 30%, respectively. At study termination, dose-related decreases in erythrocytic and leucocytic values were also observed at dietary levels of 2250 and 4500 ppm. In clinical chemistry evaluations, blood urea nitrogen levels and alkaline phosphatase activity in mice of both sexes were significantly increased at trifluralin levels of 2250 and 4500 ppm. Blood urea nitrogen also showed a marginal increase in females given the low dose of trifluralin. Alanine aminotransferase activity was significantly increased in males at all treatment levels. Although there were a number of absolute and relative organ weight changes in all three treatment groups that were significantly different from the control values, the reduced relative kidney weights in males and the increased relative liver weights in both sexes at dietary levels of 2250 and 4500 ppm were the only changes that could be correlated with altered clinical chemistry values. Apart from an increase in the incidence and severity of progressive glomerulonephritis in females of the high-dose group, there was no evidence of a treatment-related effect on any pathological condition. Chronic dietary administration of high doses of trifluralin did not cause an increase in the incidence of benign or malignant neoplasms in B6C3F1mice.