The EuroMix human biomonitoring study: Source-to-dose modeling of cumulative and aggregate exposure for the bisphenols BPA, BPS, and BPF and comparison with measured urinary levels

Karrer, Cecile; Andreassen, Monica; Goetz, Natalie von; Sonnet, Friederike; Sakhi, Amrit Kaur; Hungerbühler, Konrad; Dirven, Hubert; Husøy, Trine

doi:10.1016/j.envint.2019.105397

Cited by 45 publications

(24 citation statements)

References 54 publications

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“… 54 , 55 Another approach to estimate exposure is human biomonitoring, through analysis of CAG-specific contaminants and their metabolites in human biomaterial, particularly urine and blood. 56 , 57 , 58 Such information, combined with analysis of potential sources of the measured contaminants, can help to build and refine physiologically based pharmacokinetic models for estimating internal human exposure. 59 As explained above, exposure data of multiple contaminants can be converted into a mixture dose using RPFs, expressed as a total dose of a reference compound, where all (also low) doses of individual compounds should be included in the calculation.…”

Section: Discussionmentioning

confidence: 99%

Dose Addition in the Induction of Craniofacial Malformations in Zebrafish Embryos Exposed to a Complex Mixture of Food-Relevant Chemicals with Dissimilar Modes of Action

Ven

Ommeren

Zwart

et al. 2022

Environ Health Perspect

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Background: Humans are exposed to combinations of chemicals. In cumulative risk assessment (CRA), regulatory bodies such as the European Food Safety Authority consider dose addition as a default and sufficiently conservative approach. The principle of dose addition was confirmed previously for inducing craniofacial malformations in zebrafish embryos in binary mixtures of chemicals with either similar or dissimilar modes of action (MOAs). Objectives: In this study, we explored a workflow to select and experimentally test multiple compounds as a complex mixture with each of the compounds at or below its no observed adverse effect level (NOAEL), in the same zebrafish embryo model. Methods: Selection of candidate compounds that potentially induce craniofacial malformations was done using in silico methods—structural similarity, molecular docking, and quantitative structure–activity relationships—applied to a database of chemicals relevant for oral exposure in humans via food (EuroMix inventory, ). A final subselection was made manually to represent different regulatory fields (e.g., food additives, industrial chemicals, plant protection products), different chemical families, and different MOAs. Results: A final selection of eight compounds was examined in the zebrafish embryo model, and craniofacial malformations were observed in embryos exposed to each of the compounds, thus confirming the developmental toxicity as predicted by the in silico methods. When exposed to a mixture of the eight compounds, each at its NOAEL, substantial craniofacial malformations were observed; according to a dose–response analysis, even embryos exposed to a 7-fold dilution of this mixture still exhibited a slight abnormal phenotype. The cumulative effect of the compounds in the mixture was in accordance with dose addition (added doses of the individual compounds after adjustment for relative potencies), despite different MOAs of the compounds involved. Discussion: This case study of a complex mixture inducing craniofacial malformations in zebrafish embryos shows that dose addition can adequately predicted the cumulative effect of a mixture of multiple substances at low doses, irrespective of the (expected) MOA. The applied workflow may be useful as an approach for CRA in general. https://doi.org/10.1289/EHP9888

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Section: Discussionmentioning

confidence: 99%

Dose Addition in the Induction of Craniofacial Malformations in Zebrafish Embryos Exposed to a Complex Mixture of Food-Relevant Chemicals with Dissimilar Modes of Action

Ven

Ommeren

Zwart

et al. 2022

Environ Health Perspect

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“…Few data are currently available on the aggregate exposures of adults (dietary, nondietary, inhalation, and dermal) to these newer BPA replacement analogues, and none for TCS [40]. In a recent 2020 study, Karrer et al [40] suggested that both dietary and nondietary sources of BPS or BPF were likely important in the aggregate exposures of 144 Norwegian adults, but other relevant sources (i.e., actual food sample concentration data) were likely missing in this assessment. As data are limited, more research is needed to elucidate the important sources and routes of human exposure to these BPA replacement analogues and to TCS.…”

Section: Discussionmentioning

confidence: 99%

Exposure to Triclosan and Bisphenol Analogues B, F, P, S and Z in Repeated Duplicate-Diet Solid Food Samples of Adults

Morgan

Clifton

2021

Toxics

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Triclosan (TCS) and bisphenol analogues are used in a variety of consumer goods. Few data exist on the temporal exposures of adults to these phenolic compounds in their everyday diets. The objectives were to determine the levels of TCS and five bisphenol analogues (BPB, BPF, BPP, BPS, and BPZ) in duplicate-diet solid food (DDSF) samples of adults and to estimate maximum dietary exposures and intake doses per phenol. Fifty adults collected 776 DDSF samples over a six-week monitoring period in North Carolina in 2009–2011. The levels of the target phenols were concurrently quantified in the DDSF samples using gas chromatography/mass spectrometry. TCS (59%), BPS (32%), and BPZ (28%) were most often detected in the samples. BPB, BPF, and BPP were all detected in <16% of the samples. In addition, 82% of the total samples contained at least one target phenol. The highest measured concentration of 394 ng/g occurred for TCS in the food samples. The adults’ maximum 24-h dietary intake doses per phenol ranged from 17.5 ng/kg/day (BPB) to 1600 ng/kg/day (TCS). An oral reference dose (300,000 ng/kg/day) is currently available for only TCS, and the adult’s maximum dietary intake dose was well below a level of concern.

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“…Human biomonitoring models a. Human monitoring analysis model (Karrer et al, 2020). Measurement from biomonitoring datasets are compared with predicted exposures based on modelling dietary consumption, occurrence and/or non-dietary exposure data.…”

Section: Supra-modular Modelsmentioning

confidence: 99%

Feasibility study Open MCRA

Kruisselbrink

Lenthe

Voet

et al. 2021

EFSA Supporting Publications

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The EuroMix human biomonitoring study: Source-to-dose modeling of cumulative and aggregate exposure for the bisphenols BPA, BPS, and BPF and comparison with measured urinary levels

Cited by 45 publications

References 54 publications

Dose Addition in the Induction of Craniofacial Malformations in Zebrafish Embryos Exposed to a Complex Mixture of Food-Relevant Chemicals with Dissimilar Modes of Action

Dose Addition in the Induction of Craniofacial Malformations in Zebrafish Embryos Exposed to a Complex Mixture of Food-Relevant Chemicals with Dissimilar Modes of Action

Exposure to Triclosan and Bisphenol Analogues B, F, P, S and Z in Repeated Duplicate-Diet Solid Food Samples of Adults

Feasibility study Open MCRA

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