A flow scheme for cumulative assessment of pesticides for adverse liver effects.

The European Food Safety Authority (EFSA) is developing approaches to cumulative risk assessment by assigning pesticides to cumulative assessment groups (CAGs). For assignment to CAGs, EFSA relies on common toxic effects (CTEs) on the target system. The developed flow scheme for assignment to liver CAGs sequentially assesses the consistency of the CTE, its adversity, its potential to be secondary to other toxicities, its human relevance, and the relation of the NOAEL for the CTE to the overall NOAEL. If the responses to all questions are "yes", allocation to a CAG is supported; "no" stops the process.

Approaches for grouping of pesticides into cumulative assessment groups for risk assessment of pesticide residues in food.

The European Food Safety Authority (EFSA) is developing approaches to cumulative risk assessment of pesticides by assigning individual pesticides to cumulative assessment groups (CAGs). For assignment to CAGs, EFSA recommended to rely on adverse effects on the specific target system. Contractors to EFSA have proposed to allocate individual pesticides into CAGs relying on NOAELs for effects on target organs. This manuscript evaluates the assignments by applying EFSAs criteria to the CAGs "Toxicity to the nervous system" and "Toxicity to the thyroid hormone system (gland or hormones)". Assignment to the CAG "Toxicity to the nervous system" based, for example, on neurochemical effects like choline esterase inhibition is well supported, whereas assignment to the CAG "Toxicity to the thyroid hormone system (gland or hormones)" has been based in the examined case studies on non-reproducible effects seen in single studies or on observations that are not adverse. Therefore, a more detailed effects evaluation is required to assign a pesticide to a CAG for a target organ where many confounders regarding effects are present. Relative potency factors in cumulative risk assessment should be based on benchmark doses from studies in one species with identical study design and human relevance of effects on specific target organs should be analyzed to define minimal margins of exposure.