French C L, Yaun S S, Baldwin L A, Leonard D A, Zhao X Q, Calabrese E J
School of Public Health, University of Massachusetts, Amherst 01003, USA.
J Appl Toxicol. 1995 May-Jun;15(3):167-74. doi: 10.1002/jat.2550150306.
This study represents the first systematic attempt to rank methemoglobin-forming agents. It is a quantitative potency ranking study utilizing linear regression analysis of dose-response data for comparative purposes. Six agents that are direct-acting and eight that require bioactivation were tested for their ability to induce methemoglobin formation in Dorset sheep erythrocytes under defined in vitro conditions. The agents were then ranked according to three complementary methods based on the slope of the linear regression, the calculated dose expected to induce a given amount of methemoglobin formation and the calculated percentage methemoglobin response induced by 1 mmol l-1 of the agent. The direct-acting agents, ranked from most to least potent inducers of methemoglobin formation, are: p-dinitrobenzene > o-dinitrobenzene > copper = nitrite > chlorite > chlorate. The ranking from most to least potent inducers of the bioactivated agents are: alpha-naphthol > p-nitroaniline > m-nitroaniline, o-nitroaniline > p-nitrotoluene = aniline > m-nitrotoluene = o-nitrotoluene. The ranking procedures are discussed and issues of interindividual variation and agent-specific sensitivities are addressed.
本研究是对高铁血红蛋白形成剂进行排名的首次系统性尝试。这是一项定量效能排名研究，利用剂量反应数据的线性回归分析进行比较。在特定体外条件下，测试了六种直接作用剂和八种需要生物活化的试剂在多塞特绵羊红细胞中诱导高铁血红蛋白形成的能力。然后根据三种互补方法对这些试剂进行排名，这三种方法分别基于线性回归的斜率、预计诱导给定数量高铁血红蛋白形成的计算剂量以及由1 mmol l-1试剂诱导的计算高铁血红蛋白反应百分比。在高铁血红蛋白形成诱导剂中，从效力最强到最弱排名的直接作用剂依次为：对二硝基苯＞邻二硝基苯＞铜=亚硝酸盐＞亚氯酸盐＞氯酸盐。在生物活化试剂中，从效力最强到最弱排名依次为：α-萘酚＞对硝基苯胺＞间硝基苯胺、邻硝基苯胺＞对硝基甲苯=苯胺＞间硝基甲苯=邻硝基甲苯。讨论了排名程序，并探讨了个体间差异和试剂特异性敏感性问题。
