Guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals

Abstract

This Guidance document describes harmonised risk assessment methodologies for combined exposure to multiple chemicals for all relevant areas within EFSA's remit, i.e. human health, animal health and ecological areas. First, a short review of the key terms, scientific basis for combined exposure risk assessment and approaches to assessing (eco)toxicology is given, including existing frameworks for these risk assessments. This background was evaluated, resulting in a harmonised framework for risk assessment of combined exposure to multiple chemicals. The framework is based on the risk assessment steps (problem formulation, exposure assessment, hazard identification and characterisation, and risk characterisation including uncertainty analysis), with tiered and stepwise approaches for both whole mixture approaches and component-based approaches. Specific considerations are given to component-based approaches including the grouping of chemicals into common assessment groups, the use of dose addition as a default assumption, approaches to integrate evidence of interactions and the refinement of assessment groups. Case studies are annexed in this guidance document to explore the feasibility and spectrum of applications of the proposed methods and approaches for human and animal health and ecological risk assessment. The Scientific Committee considers that this Guidance is fit for purpose for risk assessments of combined exposure to multiple chemicals and should be applied in all relevant areas of EFSA's work. Future work and research are recommended.

Keywords: combined exposure to multiple chemicals; dose addition; harmonised methodologies; interactions; mixtures; response addition; risk assessment.

Figure 1

Tiering principles: relationships between tiers, data availability, uncertainty, accuracy and outcome of a risk assessment (from Solomon et al., 2008)

Figure 2

Overarching framework for human, animal and ecological risk assessment of combined exposure to multiple chemicals with characterisation of specific mixture aspects and inputs and outputs for each step

1. Central in red are specific aspects required for risk assessment of combined exposure to multiple chemicals; these factors require attention and/or decisions for all assessment steps in an iterative way. WMA: whole mixture approach; CBA: component‐based approach; UF: Uncertainty factors; RC: risk characterisation; DA: dose addition.

Figure 3

Problem formulation for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals

Figure 4

Examples of tiers in exposure assessments

1. Note: Occurrence and consumption data ranges from default values (tier 0) to individual co‐occurrence data and individual data, respectively (tier 3), and consequently, exposure estimates range from semi‐quantitative point estimates (tier 0) to probabilistic (tier 3). Occurrence and consumption tiers do not necessarily match.

Figure 5

Exposure assessment using the whole mixture approach

Figure 6

Exposure assessment using the component‐based approach

Figure 7

Stepwise approach for hazard identification and characterisation using a whole mixture approach

Figure 8

Stepwise approach for hazard identification and characterisation of multiple chemicals using a component‐based approach

Figure 9

Stepwise approach for risk characterisation of combined exposure to multiple chemicals

Figure D.1

Hazard characterisation of interactions between two chemicals in worker honey bees: Comparison of effect prediction using concentration addition (CA) and experimental data (observed mixture) for the characterisation of model deviation ratio (MDR)