Nesnow S
Carcinogenesis and Metabolism Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Cancer Detect Prev. 1995;19(6):465-71.
This potency scheme expands a previously reported approach (Nesnow S. Mutat Res 1990; 239:83-115) and uses as its base dose potency measured as TD50. The TD50 is converted into an inverse log scale, a decile scale, and is adjusted by weighting factors that describe other parameters of carcinogenic potency. These factors include positive or negative weightings for: the induction of tumors at tissues or organs associated with high historical control tumor incidences; the induction of malignant tumors; the induction of tumors at multiple sites; the induction of tumors in both sexes of the species; and the induction of tumors in more than one species. To express the inactivity of chemicals towards the induction of cancer, the highest average daily dose (HADD) that did not induce a statistical increase in tumors was employed. HADD values were similarly converted to log decile units and adjusted by weighting factors according to lack of activity in both sexes of a species and the lack of activity in more than one species. Three ranking schemes were developed and applied to a 225-chemical data set obtained from the National Toxicology Program Technical Reports: the carcinogen potency-F344 rat; the carcinogen potency-B6C3F1 mouse; and the carcinogen potency-combined, a potency scheme based on selecting data from either the F344 rat or B6C3F1.
这种效力方案扩展了先前报道的一种方法(Nesnow S. 《突变研究》1990年;239:83 - 115),并以作为其基础剂量的半数中毒剂量(TD50)所衡量的效力为依据。TD50被转换为逆对数尺度、十分位数尺度,并通过描述致癌效力其他参数的加权因子进行调整。这些因子包括对以下情况的正或负加权:在历史对照肿瘤发生率较高的组织或器官处诱发肿瘤;诱发恶性肿瘤;在多个部位诱发肿瘤;在该物种的两性中诱发肿瘤;以及在不止一个物种中诱发肿瘤。为了表示化学物质对诱发癌症的无活性,采用未诱发肿瘤统计学增加的最高平均日剂量(HADD)。HADD值同样被转换为对数十分位数单位,并根据在一个物种的两性中均无活性以及在不止一个物种中无活性的情况,通过加权因子进行调整。开发了三种排名方案,并将其应用于从国家毒理学计划技术报告中获取的一个包含225种化学物质的数据集:致癌物效力 - F344大鼠;致癌物效力 - B6C3F1小鼠;以及致癌物效力 - 综合方案,这是一种基于从F344大鼠或B6C3F1中选择数据的效力方案。