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目的采用基准剂量(BMD)法对某化学品90 d经口毒性试验数据进行分析,通过已明确无明显有害作用剂量和基准剂量的农药/化学品案例,将BMD法与传统的非致癌危险度评价法(NOAEL法)进行比较和讨论。方法经口灌胃大鼠某化学品0、100、300和1 000 mg/kg·bw·d,1次/d,连续90 d。观察记录大鼠中毒体征及死亡情况、体重变化、血常规、血生化、尿液检查和病理组织学检查。根据BMD法对试验的毒效应数据进行筛选,采用BMDS2.5软件,分析每一个筛选出的毒性终点数据,得出基准剂量。结果雌鼠高剂量组1 000 mg/kg·bw·d第1、3、7、8和9周体重降低、肺重量升高、脑肝肺脏器系数升高、凝血酶原时间升高,某化学品大鼠90 d经口毒性试验的NOAEL为300 mg/kg·bw·d。将具有统计学意义、毒理学意义以及显著剂量-反应趋势的数据(雌鼠肺重量、肝/肺脏器系数和凝血酶原时间)用BMD法进行分析,最终选择最敏感的毒性效应“凝血酶原时间”的基准剂量下限值(BMDL),141.7 mg/kg·bw·d,作为计算参考剂量的基础。结论在计算参考剂量时,以剂量-反应关系模型为基础的BMD法优于利用单个剂量点的NOAEL法,然而BMD法却需要更高质量的试验数据和更复杂的数据分析过程。
OBJECTIVE: To analyze the 90-day oral toxicity data of a chemical using the benchmark dose (BMD) method. The BMD method was compared with the traditional non-carcinogenicity risk through the case of pesticide / chemicals that had no obviously harmful effect dose and reference dose. Evaluation method (NOAEL method) for comparison and discussion. Methods The rats were orally gavaged with 0, 100, 300 and 1 000 mg / kg bw · d once a day for 90 d. Observe the signs and death of rats poisoning, weight changes, blood, blood biochemistry, urine tests and histopathological examination. According to the BMD method to test the toxic effects of the data screening, the use of BMDS2.5 software, analysis of each of the selected toxicity endpoint data, draw the baseline dose. Results In the high dose group of female mice, the body weight, the lung weight, the index of brain and liver increased at 1, 3, 7, 8 and 9 weeks after 1 000 mg / kg · bw · d, the prothrombin time Elevated, a chemical 90 days oral toxicity test NOAEL 300 mg / kg · bw · d. Data from the statistical, toxicological, and dose-response trends (females lung weight, liver / lung coefficient and prothrombin time) were statistically analyzed using the BMD method to ultimately select the most sensitive toxic effect The lower limit of reference dose (BMDL), 141.7 mg / kg · bw · d, was used as the basis for calculating the reference dose. Conclusions The BMD method based on the dose-response relationship model is superior to the NOAEL method using a single dose point when calculating the reference dose, whereas the BMD method requires higher quality test data and more complex data analysis.