The need to conduct dietary cumulative risk assessments for pesticidal active ingredients is provided for in the EU regulations for plant protection products (1107/2009) and Maximum Residue Levels (MRL) (396/2005). The development of respective methodologies has been ongoing at the European Food and Safety Authority (EFSA) since 2009.  Like the US EPA, EFSA started establishing Cumulative Assessment Groups (CAG) based on common toxicity. However, unlike in the US, common toxicity in the EU is defined by similar phenomenological effects on the same target organ irrespective of the mode of action. By default, no specific mechanistic data are considered to group compounds in the same CAG.<br/>So far EFSA established four acute and five chronic CAGs for the nervous system and two chronic CAGs for the thyroid. Retrospective probabilistic cumulative exposure and risk assessments have been conducted for the acute motor division and the acute and chronic Acetylcholinesterase (AChE) inhibition and the chronic hypothyroidism groups, assuming that substances from one CAG behave dose-additively, using monitoring data from the last 3 years official European Monitoring. Currently, criteria for prospective cumulative risk assessments are established in order to implement cumulative risk assessments for approval of AIs and setting of MRLs.  Although proposals for further CAGs have been drafted in External Scientific Reports for the liver, adrenals, eyes, and reproduction & development since 2016, EFSA did not yet endorse them. Crop Life Europe critically reviewed these proposals and elaborated more stringent and robust criteria to assign AIs to liver and reproductive CAGs, based on adversity, severity and human relevance of the effect, liver pathophysiological pathways, specificity of the observed effects (clear repro effect vs maternally mediated), and also the dose at which the specific effect occurs, in order to establish smaller and less redundant, specific CAGs.<br/>In future, prioritization criteria need to be applied to focus on relevant organs or toxicological pathways also considering the likelihood of co-exposures, the strength of and the dose at which the specific relevant toxicity is seen and margins of exposure. As prospective CRAs cannot be conducted using monitoring data, appropriate and realistic exposure estimates are needed in order not to block innovation in case the risk cups for some of the respective GAGs are already full.

Establishment of Cumulative Assessment Groups (CAG) and the Cumulative Risk Assessment (CRA) approach in Europe

ACS Fall 2021

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