Toxicity Weighting for Human Biomonitoring Mixture Risk Assessment: A Proof of Concept
Chemical 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 popu...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/11/5/408 |
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| author | Miranda M. Loh Phillipp Schmidt Yvette Christopher de Vries Nina Vogel Marike Kolossa-Gehring Jelle Vlaanderen Erik Lebret Mirjam Luijten |
| author_facet | Miranda M. Loh Phillipp Schmidt Yvette Christopher de Vries Nina Vogel Marike Kolossa-Gehring Jelle Vlaanderen Erik Lebret Mirjam Luijten |
| author_sort | Miranda M. Loh |
| collection | DOAJ |
| description | Chemical 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 (<i>n</i> = 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. |
| first_indexed | 2024-03-11T03:16:11Z |
| format | Article |
| id | doaj.art-34749a22e4ca473db4054ce212ab2961 |
| institution | Directory Open Access Journal |
| issn | 2305-6304 |
| language | English |
| last_indexed | 2024-03-11T03:16:11Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxics |
| spelling | doaj.art-34749a22e4ca473db4054ce212ab29612023-11-18T03:32:16ZengMDPI AGToxics2305-63042023-04-0111540810.3390/toxics11050408Toxicity Weighting for Human Biomonitoring Mixture Risk Assessment: A Proof of ConceptMiranda M. Loh0Phillipp Schmidt1Yvette Christopher de Vries2Nina Vogel3Marike Kolossa-Gehring4Jelle Vlaanderen5Erik Lebret6Mirjam Luijten7Institute of Occupational Medicine—IOM, Edinburgh EH14 4AP, UKGerman Environment Agency (UBA), 14195 Berlin, GermanyInstitute of Occupational Medicine—IOM, Edinburgh EH14 4AP, UKGerman Environment Agency (UBA), 14195 Berlin, GermanyGerman Environment Agency (UBA), 14195 Berlin, GermanyInstitute for Risk Assessment Sciences (IRAS), Utrecht University, 3584 CM Utrecht, The NetherlandsInstitute for Risk Assessment Sciences (IRAS), Utrecht University, 3584 CM Utrecht, The NetherlandsCenter for Health Protection, National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The NetherlandsChemical 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 (<i>n</i> = 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.https://www.mdpi.com/2305-6304/11/5/408human biomonitoring (HBM)chemical mixturesmixture risk assessmenttoxicity weightinghealth-based guidance value (HBGV)hazard quotient (HQ) |
| spellingShingle | Miranda M. Loh Phillipp Schmidt Yvette Christopher de Vries Nina Vogel Marike Kolossa-Gehring Jelle Vlaanderen Erik Lebret Mirjam Luijten Toxicity Weighting for Human Biomonitoring Mixture Risk Assessment: A Proof of Concept Toxics human biomonitoring (HBM) chemical mixtures mixture risk assessment toxicity weighting health-based guidance value (HBGV) hazard quotient (HQ) |
| title | Toxicity Weighting for Human Biomonitoring Mixture Risk Assessment: A Proof of Concept |
| title_full | Toxicity Weighting for Human Biomonitoring Mixture Risk Assessment: A Proof of Concept |
| title_fullStr | Toxicity Weighting for Human Biomonitoring Mixture Risk Assessment: A Proof of Concept |
| title_full_unstemmed | Toxicity Weighting for Human Biomonitoring Mixture Risk Assessment: A Proof of Concept |
| title_short | Toxicity Weighting for Human Biomonitoring Mixture Risk Assessment: A Proof of Concept |
| title_sort | toxicity weighting for human biomonitoring mixture risk assessment a proof of concept |
| topic | human biomonitoring (HBM) chemical mixtures mixture risk assessment toxicity weighting health-based guidance value (HBGV) hazard quotient (HQ) |
| url | https://www.mdpi.com/2305-6304/11/5/408 |
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