Current EU research activities on combined exposure to multiple chemicals

Abstract

Humans and wildlife are exposed to an intractably large number of different combinations of chemicals via food, water, air, consumer products, and other media and sources. This raises concerns about their impact on public and environmental health. The risk assessment of chemicals for regulatory purposes mainly relies on the assessment of individual chemicals. If exposure to multiple chemicals is considered in a legislative framework, it is usually limited to chemicals falling within this framework and co-exposure to chemicals that are covered by a different regulatory framework is often neglected. Methodologies and guidance for assessing risks from combined exposure to multiple chemicals have been developed for different regulatory sectors, however, a harmonised, consistent approach for performing mixture risk assessments and management across different regulatory sectors is lacking. At the time of this publication, several EU research projects are running, funded by the current European Research and Innovation Programme Horizon 2020 or the Seventh Framework Programme. They aim at addressing knowledge gaps and developing methodologies to better assess chemical mixtures, by generating and making available internal and external exposure data, developing models for exposure assessment, developing tools for in silico and in vitro effect assessment to be applied in a tiered framework and for grouping of chemicals, as well as developing joint epidemiological-toxicological approaches for mixture risk assessment and for prioritising mixtures of concern. The projects EDC-MixRisk, EuroMix, EUToxRisk, HBM4EU and SOLUTIONS have started an exchange between the consortia, European Commission Services and EU Agencies, in order to identify where new methodologies have become available and where remaining gaps need to be further addressed. This paper maps how the different projects contribute to the data needs and assessment methodologies and identifies remaining challenges to be further addressed for the assessment of chemical mixtures.

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

“…The internal dose, obtained through the use of biomonitoring data and/or TK models although rarely available has the potential to be used in higher tier risk characterisation (see Section 6.3) (SCHER, SCCS and SCENIHR, ). For example, human biomonitoring (HBM) for a range of multiple chemicals is being investigated in Europe with a number of monitoring programmes in Member States and through the Horizon 2020 project HBM4EU for a range of regulated chemical substances (post‐market) and contaminants (Bopp et al., ). For the animal health and the ecological area, biomonitoring data are mostly available for farm animals and wild fish, respectively.…”

Exposure to multiple air pollutants and the incidence of coronary heart disease: A fine-scale geographic analysis

“…Long-term exposure to mixtures of low-dose air pollutants have harmful effects on health (Bopp et al, 2018). However, these effects may be difficult to assess when considering conventional single- pollutant exposure because of a lack of statistical sensitivity and the multifactorial aetiology of chronic diseases.…”

Critical assessment and integration of separate lines of evidence for risk assessment of chemical mixtures

“…The integration of existing human biomonitoring (HBM) data can contribute to address combined and aggregate exposure more realistically. This approach can identify real-life exposure patterns, priority and drivers of mixture toxicity, thus allowing potential health risks of mixtures to be assessed (Bopp et al 2018).…”

“…Assessing the risk from exposure to multiple chemicals by multiple routes represents a scientific challenge. Interest in this field has intensified over the past decades as evidenced by the increasing number of articles appearing in the scientific literature (e.g., Feron et al 1998;Wilkinson et al 2000;Monosson 2005;Boobis et al 2011;Sarigiannis and Hansen 2012;Hernández et al 2013;Kienzler et al 2016;Hernández and Tsatsakis 2017) and the various meetings, technical reports, programs and documents claiming the need for additional research into the risk assessment of chemical mixtures (Bopp et al 2015;Quignot et al 2015;Rotter et al 2017;ATSDR 2018).…”

“…The European Food Safety Authority (EFSA) EFSA Panel on Plant Protection Products and their Residues (2013) recommended the use of methodologies derived from dose addition for the assessment of mixtures of pesticides with dissimilar MOA, provided they produce a common adverse outcome as no cumulative risk assessment method has been derived from independent action. Furthermore, other European Union Scientific Committees have recommended the use of the dose/concentration addition approach as a pragmatic and precautious default assumption if no MOA data are available since this concept is generally regarded as more protective (Bopp et al 2018). Recently, refined approaches have been developed for risk characterization of chemical mixtures, accounting for aggregate exposures and using toxicological reference values referred to the same critical effect/endpoint produced by the individual components of the mixture (Goumenou and Tsatsakis 2019).…”