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An investigation of the co-variation in circulating levels of a large number of environmental contaminants
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
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2012 (English)In: Journal of Exposure Science and Environmental Epidemiology, ISSN 1559-0631, E-ISSN 1559-064x, Vol. 22, no 5, 476-482 p.Article in journal (Refereed) Published
Abstract [en]

We are daily exposed to many different environmental contaminants. Mixtures of these contaminants could act together to induce more pronounced effects than the sum of the individual contaminants. To evaluate the effects of such mixtures, it is of importance to assess the co-variance amongst the contaminants. Thirty-seven environmental contaminants representing different classes were measured in blood samples from 1016 individuals aged 70 years. Hierarchical cluster analysis and principal component analysis were used to assess the co-variation among the contaminants. Within each identified cluster, possible marker contaminants were sought for. We validated our findings using data from the National Health and Nutrition Examination Survey (NHANES) 2003--2004 study. Two large clusters could be identified, one representing low/medium chlorinated polychlorinated biphenyls (PCBs) (<= 6 chlorine atoms), as well as two pesticides and one representing medium/high chlorinated PCBs (>= 6 chlorine atoms). PCBs 118 and 153 could be used as markers for the low/medium chlorinated cluster and PCBs 170 and 209 could be used as markers for the medium/high chlorinated cluster. This pattern was similar to data from the NHANES study. Apart from the PCBs, little co-variation was seen among the contaminants. Thus, a large number of chemicals have to be measured to adequately identify mixtures of environmental contaminants.

Place, publisher, year, edition, pages
2012. Vol. 22, no 5, 476-482 p.
Keyword [en]
mixtures, environmental contaminants, multivariate analysis
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-182769DOI: 10.1038/jes.2012.41ISI: 000307934000007OAI: oai:DiVA.org:uu-182769DiVA: diva2:561187
Available from: 2012-10-17 Created: 2012-10-15 Last updated: 2015-03-09Bibliographically approved
In thesis
1. Mixture Effects of Environmental Contaminants
Open this publication in new window or tab >>Mixture Effects of Environmental Contaminants
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Chemical exposure in humans rarely consists of a single chemical. The everyday exposure is characterized by thousands of chemicals mainly present at low levels. Despite that fact, risk assessment of chemicals is carried out on a chemical-by-chemical basis although there is a consensus that this view is too simplistic.

This thesis aims to validate a statistical method to study the impact of mixtures of contaminants and to use that method to investigate the associations between circulating levels of a large number of environmental contaminants and atherosclerosis and the metabolic syndrome in an elderly population. Contaminants measured in the circulation represented various classes, such as persistent organic pollutants, plastic-associated chemicals and metals.

There was little co-variation among the contaminants and only two clusters of PCBs could be discerned. Gradient boosted CARTs were used to assess additive and multiplicative associations between atherosclerosis, as measured by the intima-media thickness (IMT) and the echogenicity of the intima-media complex (IM-GSM), and prevalent metabolic syndrome.

Systolic blood pressure was the most important predictor of IMT while the influence of the contaminants was marginal. Three phthalate metabolites; MMP, MEHP and MIBP were strongly related to IM-GSM. A synergistic interaction was found for MMP and MIBP, and a small antagonistic interaction was found for MIBP and MEHP. Associations between the contaminants and prevalent metabolic syndrome were modest, but three pesticides; p,p’-DDE, hexachlorbenzene and trans-nonachlor along with PCBs 118 and 209 and mercury were the strongest predictors of prevalent metabolic syndrome.

This thesis concludes that many contaminants need to be measured to get a clear picture of the exposure. Boosted CARTs are useful for uncovering interactions. Multiplicative and/or additive effects of certain contaminant mixtures were found for atherosclerosis or the metabolic syndrome.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 85 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1059
Mixtures, Environmental Contaminants, Atherosclerosis, Metabolic Syndrome, Boosting, Epidemiology
National Category
Environmental Health and Occupational Health Probability Theory and Statistics
urn:nbn:se:uu:diva-237690 (URN)978-91-554-9122-2 (ISBN)
Public defence
2015-02-06, Frödingsalen, Ulleråkersvägen 40A, Uppsala, 09:00 (Swedish)
Available from: 2015-01-16 Created: 2014-12-04 Last updated: 2015-03-09

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Lampa, ErikLind, LarsBornefalk Hermansson, AnnaLind, P. Monica
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