Department of Chemical Safety, Federal Institute for Risk Assessment, Berlin, Germany.
Crit Rev Toxicol. 2010 Jan;40(1):24-34. doi: 10.3109/10408440903436467.
This retrospective analysis of Acute Reference Doses (ARfD) values is based on pesticides that have been evaluated and peer-reviewed in Europe between 2000 and 2008. The published database of the 198 ARfDs was analysed. For 48% of all substances, no ARfD was considered necessary because of the low acute toxicity of these pesticides. The majority of ARfDs were based on studies that were required for pesticides and conducted for regulatory purposes and in which specific acute alerts were investigated. In less than 10% of cases, conservatively established ARfDs were based on repeated-dose toxicity or multigeneration studies. For 4 of these 198 pesticides, a refinement of a conservative ARfD using an additional toxicity study would be justifiable because a more realistic calculation of the exposure component was not sufficient to eliminate any health concern. In the analysed database, special studies for ARfD refinement were submitted for 8 of the 198 pesticides. They were mostly performed in addition to the basic acute toxicity data requirements, in cases in which it was apparent that the acute intake estimation exceeded a conservatively established ARfD. However, several studies were not accepted by regulatory authorities because of quality deficiencies. The results of this analysis indicate that the development of a harmonised study design that produces consistent and robust toxicological data on the occurrence of acute effects and their dose response would be valuable for setting ARfDs. Such a protocol, plus additional research on the mode of action for acute effects observed in relevant targets for ARfD derivation, is considered as an important prerequisite for an improved acute risk assessment for pesticides.
本回顾性分析急性参考剂量 (ARfD) 值基于 2000 年至 2008 年在欧洲进行评估和同行评审的农药。分析了已发表的 198 个 ARfD 的数据库。由于这些农药的急性毒性较低，因此认为 48%的物质不需要 ARfD。大多数 ARfD 是基于为监管目的而进行的、针对农药进行的研究，并且研究了特定的急性警示。在不到 10%的情况下，基于重复剂量毒性或多代研究确定了保守的 ARfD。对于这 198 种农药中的 4 种，使用额外的毒性研究来细化保守的 ARfD 是合理的，因为仅对暴露成分进行更现实的计算不足以消除任何健康问题。在所分析的数据库中，有 8 种农药提交了用于细化 ARfD 的专门研究。这些研究主要是在基本急性毒性数据要求之外进行的，在明显急性摄入量估计值超过保守设定的 ARfD 的情况下进行。然而，由于质量缺陷，监管机构并未接受若干研究。这项分析的结果表明，制定一个协调一致的研究设计，该设计可产生关于急性效应发生及其剂量反应的一致和稳健的毒理学数据，对于设定 ARfD 将是有价值的。这样的方案，加上对用于推导 ARfD 的相关靶标中观察到的急性效应的作用模式的进一步研究，被认为是改进农药急性风险评估的重要前提。
