A retain and refine approach to cumulative risk assessment. (April 2020)

• Record Type: Journal Article
• Authors: Kennedy, Marc C.; Hart, Andy D.M.; Kruisselbrink, Johannes W.; van Lenthe, Marco; de Boer, Waldo J.; van der Voet, Hilko; Rorije, Emiel; Sprong, Corinne; van Klaveren, Jacob
• Is Part Of: Food and chemical toxicology. Volume 138(2020)
• Publication Date: 2020-04
• Subjects: Pesticides -- Mixtures -- Uncertainty -- Cumulative assessment group -- QSAR -- Relative potency factor; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2020.111223
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Mixtures of substances to which humans are exposed may lead to cumulative exposure and health effects. To study their effects, it is first necessary to identify a cumulative assessment group (CAG) of substances for risk assessment or hazard testing. Excluding substances from consideration before there is sufficient evidence may underestimate the risk. Conversely, including everything and treating the inevitable uncertainties using conservative assumptions is inefficient and may overestimate the risk, with an unknown level of protection. An efficient, transparent strategy is described to retain a large group, quantifying the uncertainty of group membership and other uncertainties. Iterative refinement of the CAG then focuses on adding information for the substances with high probability of contributing significantly to the risk. Probabilities can be estimated using expert opinion or derived from data on substance properties. An example is presented with 100 pesticides, in which the retain step identified a single substance to target refinement. Using an updated hazard characterisation for this substance reduced the mean exposure estimate from 0.43 to 0.28 μg kg-bw −1 day −1 and reduced the 99.99th percentile exposure from 24.9 to 5.1 μg kg-bw −1 day −1 . Other retained substances contributed little to the risk estimates, even after accounting for uncertainty. Highlights: The EuroMix project has developed strategies for selecting substances in a cumulative assessment group (CAG). Probability of CAG membership of each substance can be calculated using QSAR data or using expert opinion. A tiered approach and uncertainty quantification allows efficient identification of potentially important substances. Uncertainties in CAG membership, missing hazard data and other aspects can be quantified in a retain and refine strategy. Updating hazard data on a single substance reduced exposure uncertainty substantially in a test example with 100 substances.