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.

This publication is linked to the following EFSA Journal article: http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2021.6769/full This publication is linked to the following EFSA Supporting Publicat...

Although fish intake has potential health benefits, the presence of metal contamination in seafood has raised public health concerns. In this study, levels of mercury, cadmium, lead, tin and arsenic have been determined in fresh, canned and frozen fish and shellfish products and compared with the maximum levels currently in force. In a further step, potential human health risks for the consumers were assessed. A total of 485 samples of the 43 most frequently consumed fish and shellfish species in Andalusia (Southern Spain) were analyzed for their toxic elements content. High mercury concentrations were found in some predatory species (blue shark, cat shark, swordfish and tuna), although they were below the regulatory maximum levels. In the case of cadmium, bivalve mollusks such as canned clams and mussels presented higher concentrations than fish, but almost none of the samples analyzed exceeded the maximum levels. Lead concentrations were almost negligible with the exception of frozen common sole, which showed median levels above the legal limit. Tin levels in canned products were far below the maximum regulatory limit, indicating that no significant tin was transferred from the can. Arsenic concentrations were higher in crustaceans such as fresh and frozen shrimps. The risk assessment performed indicated that fish and shellfish products were safe for the average consumer, although a potential risk cannot be dismissed for regular or excessive consumers of particular fish species, such as tuna, swordfish, blue shark and cat shark (for mercury) and common sole (for lead).

The Scientific Committee confirms that the Threshold of Toxicological Concern (TTC) is a pragmatic screening and prioritisation tool for use in food safety assessment. This Guidance provides clear step‐by‐step instructions for use of the TTC approach. The inclusion and exclusion criteria are defined and the use of the TTC decision tree is explained. The approach can be used when the chemical structure of the substance is known, there are limited chemical‐specific toxicity data and the exposure can be estimated. The TTC approach should not be used for substances for which EU food/feed legislation requires the submission of toxicity data or when sufficient data are available for a risk assessment or if the substance under consideration falls into one of the exclusion categories. For substances that have the potential to be DNA‐reactive mutagens and/or carcinogens based on the weight of evidence, the relevant TTC value is 0.0025 μg/kg body weight (bw) per day. For organophosphates or carbamates, the relevant TTC value is 0.3 μg/kg bw per day. All other substances are grouped according to the Cramer classification. The TTC values for Cramer Classes I, II and III are 30 μg/kg bw per day, 9 μg/kg bw per day and 1.5 μg/kg bw per day, respectively. For substances with exposures below the TTC values, the probability that they would cause adverse health effects is low. If the estimated exposure to a substance is higher than the relevant TTC value, a non‐TTC approach is required to reach a conclusion on potential adverse health effects.