MMTGS Limited, Congleton, United Kingdom.
Gowan Crop Protection, Reading, United Kingdom.
Regul Toxicol Pharmacol. 2020 Jun;113:104638. doi: 10.1016/j.yrtph.2020.104638. Epub 2020 Mar 8.
To protect human health, acute reference values have been established for pesticides which have the potential to cause a toxic effect after acute human exposure. These values are used to identify exposure levels below which there is no appreciable risk. Comprehensive reference documents, including OECD criteria, are available to aid identification of relevant toxicological endpoints. Within Europe, there is a concern that the identification process is inconsistent and unnecessarily conservative such that safe products with no established human health risk are being restricted. For this reason, the basis for the setting of an acute reference dose (ARfD) has been investigated for 130 pesticides to better understand how the toxicological endpoints are selected. The investigation has shown that most ARfDs are derived from repeat dose studies and that there is an over-representation of prenatal developmental toxicity studies. There is clear evidence that ARfDs derived from rabbit developmental toxicity studies are set over conservatively with regard to acute maternal effects and often inappropriately. To facilitate an improved system, refinements to the existing process are recommended, the use of maternal data in the rabbit as the basis for deriving an ARfD is critically evaluated and a new, more pragmatic approach to ARfD derivation is proposed.
为了保护人类健康，已经为那些在人类急性暴露后可能产生毒性影响的农药制定了急性参考值。这些值用于确定低于无明显风险的暴露水平。有综合性的参考文件，包括经合组织标准，可帮助确定相关的毒理学终点。在欧洲，人们担心识别过程不一致且过于保守，以至于安全的产品没有建立人类健康风险却受到限制。出于这个原因，已经针对 130 种农药对急性参考剂量 (ARfD) 的设定依据进行了调查，以更好地了解如何选择毒理学终点。调查表明，大多数 ARfD 源自重复剂量研究，并且产前发育毒性研究的代表性过高。有明确的证据表明，从兔发育毒性研究中得出的 ARfD 在急性母体效应方面设定得过于保守，而且常常不恰当。为了促进一个改进的系统，建议对现有的过程进行改进，批判性地评估在兔中使用母体数据作为推导 ARfD 的基础，并提出一种新的、更务实的 ARfD 推导方法。
