Dow AgroSciences, Abingdon, United Kingdom.
Crit Rev Toxicol. 2010 Jan;40(1):35-49. doi: 10.3109/10408440903367741.
Regulatory tests investigating pesticide carcinogenicity potential routinely comprise a battery of in vitro and in vivo genotoxicity studies and two cancer bioassays, one in rats and one in mice. The genotoxicity testing strategy essentially ensures that genotoxic compounds are eliminated, and any carcinogens identified in subsequent lifetime studies are probably nongenotoxic in character. Assessment of 202 pesticide evaluations from the European Union review programme under Directive 91/414/EEC indicated that the mouse carcinogenicity study contributed little or nothing to either derivation of an acceptable daily intake (ADI) for assessment of chronic risk to humans, or hazard classification for labelling purposes. From a pesticide approval perspective, the mouse study did not influence a single outcome. From a risk assessment perspective, the ADI for just one pesticide was based on tumours in mice and this would have barely changed if the mouse data had not been available. In total, only 10 (5%) pesticide ADIs were based solely on the mouse carcinogenicity study and even in these few cases, a similar value would have been identified from other studies if the mouse study had not been available. For pesticides with treatment-related tumours only in mice, just three, or 1.5%, were classified as carcinogens and all were in the lowest category, Category 3 (R40). For pesticides with treatment-related tumours in mice and rats, the mouse data were probably the main, if not the only, cause for another three cases of R40 classification. Absence of the mouse studies would not have influenced assignment of the higher, Category 2 (R45), cancer classification for any substance with treatment-related tumours in both species as all decisions for these substances were limited to Category 3 or 'unclassified' outcomes. Over 100,000 mice were used to test these pesticides. This review shows that the mouse carcinogenicity studies did not provide significant information over and above that provided by the rat studies, and underpins the opportunity, from both a scientific and an animal welfare perspective, to remove the mouse carcinogenicity study from regulatory data requirements for the testing of pesticides.
监管测试调查农药致癌潜力通常包括一系列体外和体内遗传毒性研究和两个癌症生物测定，一个在大鼠和一个在小鼠。遗传毒性测试策略基本上确保了遗传毒性化合物被消除，并且在随后的终身研究中发现的任何致癌物质可能具有非遗传毒性特征。对欧盟审查计划下指令 91/414/EEC 的 202 种农药评估的评估表明，小鼠致癌性研究对推导可接受的每日摄入量（ADI）以评估人类慢性风险或标签目的的危害分类几乎没有贡献。从农药批准的角度来看，该小鼠研究没有影响任何一个结果。从风险评估的角度来看，只有一种农药的 ADI 基于小鼠肿瘤，而如果没有小鼠数据，ADl 几乎不会改变。总共只有 10 种（5%）农药 ADI 仅基于小鼠致癌性研究，即使在这些少数情况下，如果没有小鼠研究，也可以从其他研究中确定类似的值。对于仅在小鼠中具有治疗相关肿瘤的农药，只有三种或 1.5%被归类为致癌物质，并且全部属于最低类别 3 类（R40）。对于在小鼠和大鼠中具有治疗相关肿瘤的农药，小鼠数据可能是另外三种 R40 分类的主要原因，如果不是唯一原因。如果没有进行小鼠研究，则不会影响将任何具有两种物种中治疗相关肿瘤的物质的更高类别 2（R45）癌症分类，因为所有这些物质的决定都限于类别 3 或“未分类”的结果。超过 100,000 只小鼠用于测试这些农药。这项审查表明，小鼠致癌性研究没有提供比大鼠研究提供的更多的信息，并从科学和动物福利的角度为消除农药测试的监管数据要求中的小鼠致癌性研究提供了机会。
