A review of cumulative risk assessment of multiple pesticide residues in food: Current status, approaches and future perspectives

The widespread application of pesticides in agricultural production often leads to the occurrence of multiple pesticide residues in food, which have the potential to accumulate within the human body and cause cumulative health risks. In order to address this matter, regulatory measures have been established to ensure the incorporation of cumulative effects in the risk assessment for pesticides. This review provides an in-depth look at the current status of cumulative risk assessment (CRA) of multiple pesticide residues in food, highlighting recent advances in regulations, methods for grouping pesticides, characterization of the cumulative hazard and risk, and the suitability of dose-addition assumptions, as well as data requirements. In addition, case studies of CRA for pesticide residues that have been conducted globally are also collected, which effectively assist in assessing the actual cumulative exposure risks associated with pesticide residues and informing the establishment of maximum residue limits (MRLs) in food. Further, the development of new assessment methods is summarized, including the incorporation of mixture assessment factors (MAF), adverse outcome pathway (AOP) networks, as well as the methodologies for prioritizing the main drivers of the cumulative risk and grouping pesticides based on their interactions related to toxicokinetic interference. Key findings and conclusions: This review emphasizes the importance of regularly conducting retrospective and prospective cumulative risk assessments to incorporate changes in exposure patterns and updates to the cumulative assessment group (CAG). Global research has shown that significant health risks from cumulative pesticide exposure arise primarily under highly conservative assumptions, with a limited set of pesticides primarily affecting CRA outcomes. This finding suggests that future research focus on specific pesticide/commodity combinations and their cumulative effects. Finally, it is highlighted that incorporating the new assessment methods will allow for more accurate information for risk assessment, informing pesticide authorizations and regulatory limit settings.