Occupational exposure to metals and PAHs: combining literature-based exposure and in vitro hazard data towards a mixture risk assessment a mixture risk assessment

The environment within industrial settings is commonly characterized by the existence of a complex mixture of chemicals from different raw materials and transformation processes. Occupational co-exposure to chromium (Cr), Nickel (Ni), and Polycyclic Aromatic Hydrocarbons (PAHs) may occur in diverse workplaces, such as the aeronautic and waste management, (e.g incineration) sectors. Such co-exposure rais-es concern in terms of occupational health, as these substances are recognized lung carcinogens and mainly act by genotoxic mechanisms, increasing the likelihood of interactive toxic effects. The fact that cur-rent regulatory practices are usually focused on single chemical sub-stances, without integrating the possibility of combined or aggregated exposures and effects, may lead to a risk underestimation.In this work, developed under the scope of HBM4EU Initiative (https://www.hbm4eu.eu), a literature-based mixture risk assess-ment (MRA) exercise for occupational exposure to metals and PAHs was performed. In addition, in vitro toxicity data was obtained for the same mixtures to provide support to its hazard assessment.Human biomonitoring (HBM) data on Cr(VI), Ni and/or PAHs was extracted from occupational studies conducted in the European Un-ion and searched in literature databases. Selected reference values were used to calculate risk quotients (RQ) for each substance based on the retrieved exposure data; the combined risk was given by the sum of the RQ, i.e., the Background Exposure Exceedance Score(BEES).In parallel, we evaluated the combined cyto- and genotoxicity of the same chemicals (assessed by the MTT and micronucleus assays) in the human alveolar A549 cell line.In most of the analysed studies, we observed that BEES levels, estimated from the exposure to metals mixture or to metals and PAHs, exceeded RQ levels considered acceptable for the individual substances. Only two studies, conducted in hazard waste incinerator settings, presented urinary exposure levels for the three substances. They showed a value of BEES of concern (>1) for all exposure sce-narios, even for workers performing activities considered of low ex-posure or no-exposure, such as laboratory and administrative work-ers. In vitro assays supported that A549 cells exposure to these substances resulted in interactive cytotoxic and genotoxic effects that may underlie health effects different from those predicted from single exposures.Our findings show the limitations of applying occupational expo-sure reference values defined on a single substance basis to work-places where exposure to chemical mixtures occur, highlighting the relevance of performing MRA as a more realistic approach to guide suitable risk management measures in occupational settings