Abstract
Human biomonitoring (HBM) data can provide insight into co-exposure patterns resulting from exposure to multiple chemicals from various sources and over time. Therefore, such data are particularly valuable for assessing potential risks from combined exposure to multiple chemicals.One way to interpret HBM data is establishing safe levels in blood or urine, called Biomonitoring Equivalents (BE) or HBM health based guidance values (HBM-HBGV). These can be derived by converting established external reference values, such as tolerable daily intake (TDI) values. HBM-HBGV or BE values are so far agreed only for a very limited number of chemicals. These values can be established using physiologically based kinetic (PBK) modelling, usually requiring substance specific models and the collection of many input parameters which are often not available or difficult to find in the literature.The aim of this study was to investigate the suitability and limitations of generic PBK models in deriving BE values for several compounds with a view to facilitating the use of HBM data in the assessment of chemical mixtures at a screening level. The focus was on testing the methodology with two generic models, the IndusChemFate tool and High-Throughput Toxicokinetics package, for two different classes of compounds, phenols and phthalates. HBM data on Danish children and on Norwegian mothers and children were used to evaluate the quality of the predictions and to illustrate, by means of a case study, the overall approach of applying PBK models to chemical classes with HBM data in the context of chemical mixture risk assessment.Application of PBK models provides a better understanding and interpretation of HBM data. However, the study shows that establishing safety threshold levels in urine is a difficult and complex task. The approach might be more straightforward for more persistent chemicals that are analysed as parent compounds in blood but high uncertainties have to be considered around simulated metabolite concentrations in urine. Refining the models may reduce these uncertainties and improve predictions. Based on the experience gained with this study, the performance of the models for other chemicals could be investigated, to improve the accuracy of the simulations.
Highlights
Human biomonitoring (HBM) allows assessment of exposure to chemicals by measuring these compounds, their metabolites or other biomarkers of exposure present in body fluids or other biological matrices
Calculations for Norwegian women and children Using the calculated estimated daily intakes (EDIs) from external sources of the Norwegian data set, the corresponding urinary concentrations based on estimated daily intakes (BEEDIs) were simulated with ICF and compared to the measured urinary concentrations in the Norwegian HBM dataset
For DnBP and BBzB, estimated EDI-based urine concentrations (BEEDI) are always lower than measured urine concentrations. This could indicate that there are other external sources of these chemicals that were not covered in calculating the EDI, but it can indicate that ICF is underpredicting
Summary
Human biomonitoring (HBM) allows assessment of exposure to chemicals by measuring these compounds, their metabolites or other biomarkers of exposure present in body fluids (blood, urine, saliva, breast milk) or other biological matrices (hair, nails and teeth). Monitoring of indoor and outdoor media (air and dust), and chemical exposure associated with food intake via diet diaries can be collected together with information on study participants' age, sex, socioeconomic background to give a more complete picture of external and internal exposure and to link human exposure to exposure sources and epidemiological survey data. One example is the American HBM programme (National Health and Nutrition Examination Survey, NHANES), the largest ongoing project running since 1971 (McDowell, 1971). In the Democophes project, mother–child pairs over large parts of Europe were studied (Den Hond et al, 2015) and in 2017 a project was launched by the European Commission called “The European Human Biomonitoring Initiative” (HBM4EU) which is a joint effort of 30 European countries. The aim of the project is to collect and interpret HBM data throughout Europe in order to safely manage chemicals and protect human health (HBM4EU, 2019). The long-term goal is to build bridges between the research and policy worlds and deliver benefits to society in terms of enhanced chemical safety
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