A retrospective analysis of Acute Reference Doses for pesticides evaluated in the European Union.

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.