Toxicity Weighting for Human Biomonitoring Mixture Risk Assessment: A Proof of Concept.

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dc.contributor.authorLoh, Miranda M
dc.contributor.authorSchmidt, Phillipp
dc.contributor.authorChristopher de Vries, Yvette
dc.contributor.authorVogel, Nina
dc.contributor.authorKolossa-Gehring, Marike
dc.contributor.authorVlaanderen, Jelle
dc.contributor.authorLebret, Erik
dc.contributor.authorLuijten, Mirjam
dc.date.accessioned2023-05-30T11:37:03Z
dc.date.available2023-05-30T11:37:03Z
dc.date.issued2023-04-26
dc.description.abstractChemical mixture risk assessment has, in the past, primarily focused on exposures quantified in the external environment. Assessing health risks using human biomonitoring (HBM) data provides information on the internal concentration, from which a dose can be derived, of chemicals to which human populations are exposed. This study describes a proof of concept for conducting mixture risk assessment with HBM data, using the population-representative German Environmental Survey (GerES) V as a case study. We first attempted to identify groups of correlated biomarkers (also known as 'communities', reflecting co-occurrence patterns of chemicals) using a network analysis approach (n = 515 individuals) on 51 chemical substances in urine. The underlying question is whether the combined body burden of multiple chemicals is of potential health concern. If so, subsequent questions are which chemicals and which co-occurrence patterns are driving the potential health risks. To address this, a biomonitoring hazard index was developed by summing over hazard quotients, where each biomarker concentration was weighted (divided) by the associated HBM health-based guidance value (HBM-HBGV, HBM value or equivalent). Altogether, for 17 out of the 51 substances, health-based guidance values were available. If the hazard index was higher than 1, then the community was considered of potential health concern and should be evaluated further. Overall, seven communities were identified in the GerES V data. Of the five mixture communities where a hazard index was calculated, the highest hazard community contained N-Acetyl-S-(2-carbamoyl-ethyl)cysteine (AAMA), but this was the only biomarker for which a guidance value was available. Of the other four communities, one included the phthalate metabolites mono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) with high hazard quotients, which led to hazard indices that exceed the value of one in 5.8% of the participants included in the GerES V study. This biological index method can put forward communities of co-occurrence patterns of chemicals on a population level that need further assessment in toxicology or health effects studies. Future mixture risk assessment using HBM data will benefit from additional HBM health-based guidance values based on population studies. Additionally, accounting for different biomonitoring matrices would provide a wider range of exposures. Future hazard index analyses could also take a common mode of action approach, rather than the more agnostic and non-specific approach we have taken in this proof of concept.en_US
dc.identifier.doi10.3390/toxics11050408
dc.identifier.eissn2305-6304
dc.identifier.journalToxics 2023;11(5):408en_US
dc.identifier.pmid37235224
dc.identifier.urihttp://hdl.handle.net/10029/626721
dc.language.isoenen_US
dc.source.countrySwitzerland
dc.source.issue5
dc.source.journaltitleToxics
dc.source.volume11
dc.subjectHBM4EUen_US
dc.subjectbiomonitoring equivalent (BE)en_US
dc.subjectchemical mixturesen_US
dc.subjecthazard index (HI)en_US
dc.subjecthazard quotient (HQ)en_US
dc.subjecthealth-based guidance value (HBGV)en_US
dc.subjecthuman biomonitoring (HBM)en_US
dc.subjectmixture risk assessmenten_US
dc.subjecttoxicity weightingen_US
dc.titleToxicity Weighting for Human Biomonitoring Mixture Risk Assessment: A Proof of Concept.en_US
dc.typeArticleen_US
dspace.entity.typePublication
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