Nesnow S
Carcinogenesis and Metabolism Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Environ Health Perspect. 1991 Dec;96:17-21. doi: 10.1289/ehp.919617.
A scheme for ranking the quantitative activity of chemical carcinogens is described. This activity scheme uses as its base dose potency measured as TD50 which after conversion into an inverse log scale, a decile scale, is adjusted by weighting factors that described other parameters of carcinogenic activity. 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 tumors at multiple sites; the induction of tumors in both sexes of the species; and the induction of tumors in more than one species. These factors were chosen because they represented qualitative descriptions of the general specificity or nonspecificity of chemicals with regard to the activity in rodents and have some bearing on the potential activity of chemicals in humans. To construct a measure to express the inactivity of chemicals toward the induction of cancer, a measure analogous to the TD50 has been developed: highest average daily dose (HADD) in milligrams chemical/kilogram body weight administered in a chronic cancer study and that did not induce a statistical increase in tumors. 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.(ABSTRACT TRUNCATED AT 250 WORDS)
本文描述了一种对化学致癌物定量活性进行排名的方案。该活性方案以经转化为对数倒数尺度(十分位数尺度)的半数肿瘤发生剂量(TD50)所衡量的剂量效力为基础,并通过描述致癌活性其他参数的加权因子进行调整。这些因子包括对在历史对照肿瘤发生率较高的组织或器官诱导肿瘤的正加权或负加权;在多个部位诱导肿瘤;在该物种的雌雄两性中均诱导肿瘤;以及在不止一个物种中诱导肿瘤。选择这些因子是因为它们代表了化学物质在啮齿动物中活性的一般特异性或非特异性的定性描述,并且与化学物质在人类中的潜在活性有一定关联。为构建一种衡量化学物质诱导癌症无活性的指标,已开发出一种类似于TD50的指标:在慢性癌症研究中给予的、未导致肿瘤统计学增加的、以毫克化学物质/千克体重计的最高平均日剂量(HADD)。HADD值同样转换为对数十分位数单位,并根据在一个物种的雌雄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。(摘要截短于250字)