Combined chronic dietary exposure to four nephrotoxic metals exceeds tolerable intake levels in the adult population of 10 European countries

Abstract

A mixture risk assessment (MRA) for four metals relevant to chronic kidney disease (CKD) was performed. Dietary exposure to cadmium or lead alone exceeded the respective reference values in the majority of the 10 European countries included in our study. When the dietary exposure to those metals and inorganic mercury and inorganic arsenic was combined following a classical or personalised modified reference point index (mRPI) approach, not only high exposure (95th percentile) estimates but also the mean exceeded the tolerable intake of the mixture in all countries studied. Cadmium and lead contributed most to the combined exposure, followed by inorganic arsenic and inorganic mercury. The use of conversion factors for inorganic arsenic and inorganic mercury from total arsenic and total mercury concentration data was a source of uncertainty. Other uncertainties were related to the use of different principles to derive reference points. Yet, MRA at the target organ level, as performed in our study, could be used as a way to efficiently prioritise assessment groups for higher-tier MRA. Since the combined exposure to the four metals exceeded the tolerable intake, we recommend a refined MRA based on a common, specific nephrotoxic effect and relative potency factors (RPFs) based on a similar effect size.

Keywords:

• Cadmium
• lead
• inorganic arsenic
• inorganic mercury
• nephrotoxicity
• combined exposure

Acknowledgements

The authors would like to thank Matthijs Sam (RIVM) for his help in organising the food consumption data and chemical concentration data, Jan Dirk Te Biesebeek (RIVM) for his help with the exposure assessment, EFSA for providing the food consumption databases, and data owners for giving permission to use the data.

Disclosure statement

The authors report there are no competing interests to declare.

Additional information

Funding

The work performed for this article started in the HBM4EU project which received funding from the European Union’s Horizon 2020 research and innovation program under Grant Agreement No. 733032 (ADvdB, GvD, ERG, ML and MJBM) and was completed in the framework of the European Partnership for the Assessment of Risks from Chemicals (PARC) which received funding from the European Union’s Horizon Europe Research and Innovation Programme under Grant Agreement No. 101057014 (RCS, AC, AM and JDvK) and Horizon 2020 Framework Programme.