Use of dislodgeable foliar residue studies for the evaluation of isomerization potential of active substances for non-dietary risk assessment

by Silke Wagner, Christian J. Kuster

When assessing the non-dietary risks for operators, workers, bystanders and residents to active substances in plant protection products (PPPs) that contain stereoisomers, the EFSA guidance on stereoisomers recommends the application of uncertainty factors when the initial ratio of stereoisomers undergoes a significant stereoisomeric excess change of more than 10%. This precautionary approach may be over-conservative in cases where the change in isomers is due to differences in their degradation rates rather than conversion of one isomer to a potentially more toxic isomer. Therefore, the impact of isomeric composition in non-dietary risk assessments of PPPs was evaluated, with particular emphasis on dislodgeable foliar residues (DFR) data and potential enantioselective degradation processes. Hypothetical outcomes are discussed as well as an evaluation of data for 5 compounds from a total of 35 DFR studies conducted under GLP, aimed at deriving DFR values for higher tier assessments. The findings indicate that possible isomerization of the active substance on leaves can be detected in DFR studies, which is essential for assessing risks to workers and residents. The results of this evaluation highlight the potential for over-conservatism of the current EFSA method for calculating uncertainty factors in non-dietary risk assessments. The EFSA method’s reliance on worst-case assumptions, coupled with the lack of a formal statistical basis, can lead to overestimation of exposure, as illustrated in our theoretical considerations and supported by empirical data from DFR studies. To address this, we propose an alternative approach to evaluating risk considering both degradation and interconversion rates.