We performed a mixture risk assessment (MRA) case study of dietary exposure to the food contaminants lead, methylmercury, inorganic arsenic (iAs), fluoride, non-dioxin-like polychlorinated biphenyls (NDL-PCBs) and polybrominated diphenyl ethers (PBDEs), all substances associated with declines in cognitive abilities measured as IQ loss. Most of these chemicals are frequently measured in human biomonitoring studies. A component-based, personalised modified reference point index (mRPI) approach, in which we expressed the exposures and potencies of our chosen substances as lead equivalent values, was applied to perform a MRA for dietary exposures. We conducted the assessment for four different age groups (toddlers, children, adolescents, and women aged 18-45 years) in nine European countries. Populations in all countries considered exceeded combined tolerable levels at median exposure levels. NDL-PCBs in fish, other seafood and dairy, lead in grains and fruits, methylmercury in fish and other seafoods, and fluoride in water contributed most to the combined exposure. We identified uncertainties for the likelihood of co-exposure, assessment group membership, endpoint-specific reference values (ESRVs) based on epidemiological (lead, methylmercury, iAs, fluoride and NDL-PCBs) and animal data (PBDE), and exposure data. Those uncertainties lead to a complex pattern of under- and overestimations, which would require probabilistic modelling based on expert knowledge elicitation for integration of the identified uncertainties into an overall uncertainty estimate. In addition, the identified uncertainties could be used to refine future MRA for cognitive decline.

AGES Austrian Agency for Health and Food Safety Spargelfeldstraße 191 1220 Vienna Austria

ANSES French Agency for Food Environmental and Occupational Health and Safety Risk Assessment Department Methodology and Studies Unit 947001 Maisons Alfort France

Brunel University London Centre for Pollution Research and Policy Uxbridge UB8 3PH United Kingdom

HAPIH Croatian Agency for Agriculture and Food Vinkovačka cesta 63C 31000 Osijek Croatia

National Institute of Public Health Environmental Health Centre Trubarjeva 2 Ljubljana Slovenia

National Institute of Public Health Prague Centre for Health Nutrition and Food Brno Czech Republic

RIVM National Institute for Public Health and the Environment PO Box 1 3720 BA Bilthoven the Netherlands

State General Laboratory Ministry of Health Nicosia Cyprus

Technical University of Denmark National Food Institute Research group for Chemical Risk Assessment and GMO Kemitorvet Building 201 DK 2800 Lyngby Denmark

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$a A case study of neurodevelopmental risks from combined exposures to lead, methyl-mercury, inorganic arsenic, polychlorinated biphenyls, polybrominated diphenyl ethers and fluoride / $c C. Sprong, JD. Te Biesebeek, M. Chatterjee, G. Wolterink, A. van den Brand, U. Blaznik, D. Christodoulou, A. Crépet, B. Hamborg Jensen, D. Sokolić, E. Rauscher-Gabernig, J. Ruprich, A. Kortenkamp, J. van Klaveren

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$a We performed a mixture risk assessment (MRA) case study of dietary exposure to the food contaminants lead, methylmercury, inorganic arsenic (iAs), fluoride, non-dioxin-like polychlorinated biphenyls (NDL-PCBs) and polybrominated diphenyl ethers (PBDEs), all substances associated with declines in cognitive abilities measured as IQ loss. Most of these chemicals are frequently measured in human biomonitoring studies. A component-based, personalised modified reference point index (mRPI) approach, in which we expressed the exposures and potencies of our chosen substances as lead equivalent values, was applied to perform a MRA for dietary exposures. We conducted the assessment for four different age groups (toddlers, children, adolescents, and women aged 18-45 years) in nine European countries. Populations in all countries considered exceeded combined tolerable levels at median exposure levels. NDL-PCBs in fish, other seafood and dairy, lead in grains and fruits, methylmercury in fish and other seafoods, and fluoride in water contributed most to the combined exposure. We identified uncertainties for the likelihood of co-exposure, assessment group membership, endpoint-specific reference values (ESRVs) based on epidemiological (lead, methylmercury, iAs, fluoride and NDL-PCBs) and animal data (PBDE), and exposure data. Those uncertainties lead to a complex pattern of under- and overestimations, which would require probabilistic modelling based on expert knowledge elicitation for integration of the identified uncertainties into an overall uncertainty estimate. In addition, the identified uncertainties could be used to refine future MRA for cognitive decline.

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$a Te Biesebeek, Jan Dirk $u RIVM, National Institute for Public Health and the Environment, PO Box 1, 3720 BA, Bilthoven, the Netherlands

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$a Chatterjee, Mousumi $u Brunel University London, Centre for Pollution Research and Policy, Uxbridge, UB8 3PH, United Kingdom

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$a Wolterink, Gerrit $u RIVM, National Institute for Public Health and the Environment, PO Box 1, 3720 BA, Bilthoven, the Netherlands

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$a Blaznik, Urska $u National Institute of Public Health, Environmental Health Centre, Trubarjeva 2, Ljubljana, Slovenia

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$a Ruprich, Jiri $u National Institute of Public Health in Prague, Centre for Health, Nutrition and Food, Brno, Czech Republic

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$a Kortenkamp, Andreas $u Brunel University London, Centre for Pollution Research and Policy, Uxbridge, UB8 3PH, United Kingdom

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$a van Klaveren, Jacob $u RIVM, National Institute for Public Health and the Environment, PO Box 1, 3720 BA, Bilthoven, the Netherlands

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