Ten years of research on synergisms and antagonisms in chemical mixtures: A systematic review and quantitative reappraisal of mixture studies

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• Systematic review and quantitative reappraisal of 10 years’ of experimental mixture studies.

• Inventory of 1220 mixture experiments subjected to subgroup analyses.

• Quantitative reappraisal of 557 claimed deviations from expected additivity, classed by their authors as synergisms, antagonism, interactions or potentiations.

• Few claims of synergistic or antagonistic effects exceeded the boundaries of acceptable between-study variability.

• Results confirm the utility of default application of the dose (concentration) addition concept for predictive assessments of simultaneous exposures to multiple chemicals.

• Application of dose addition must be complemented by an awareness of the synergistic potential of specific classes of chemicals.

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