Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Mixture Effects of Environmental Contaminants
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
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.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1059
Keyword [en]
Mixtures, Environmental Contaminants, Atherosclerosis, Metabolic Syndrome, Boosting, Epidemiology
National Category
Environmental Health and Occupational Health Probability Theory and Statistics
Identifiers
URN: urn:nbn:se:uu:diva-237690ISBN: 978-91-554-9122-2 (print)OAI: oai:DiVA.org:uu-237690DiVA: diva2:768489
Public defence
2015-02-06, Frödingsalen, Ulleråkersvägen 40A, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2015-01-16 Created: 2014-12-04 Last updated: 2015-03-09
List of papers
1. An investigation of the co-variation in circulating levels of a large number of environmental contaminants
Open this publication in new window or tab >>An investigation of the co-variation in circulating levels of a large number of environmental contaminants
Show others...
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.

Keyword
mixtures, environmental contaminants, multivariate analysis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-182769 (URN)10.1038/jes.2012.41 (DOI)000307934000007 ()
Available from: 2012-10-17 Created: 2012-10-15 Last updated: 2017-12-07Bibliographically approved
2. The identification of complex interactions in epidemiology and toxicology: a simulation study of Boosted Regression Trees
Open this publication in new window or tab >>The identification of complex interactions in epidemiology and toxicology: a simulation study of Boosted Regression Trees
2014 (English)In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 13, 57- p.Article in journal (Refereed) Published
Abstract [en]

Background: There is a need to evaluate complex interaction effects on human health, such as those induced by mixtures of environmental contaminants. The usual approach is to formulate an additive statistical model and check for departures using product terms between the variables of interest. In this paper, we present an approach to search for interaction effects among several variables using boosted regression trees. Methods: We simulate a continuous outcome from real data on 27 environmental contaminants, some of which are correlated, and test the method's ability to uncover the simulated interactions. The simulated outcome contains one four-way interaction, one non-linear effect and one interaction between a continuous variable and a binary variable. Four scenarios reflecting different strengths of association are simulated. We illustrate the method using real data. Results: The method succeeded in identifying the true interactions in all scenarios except where the association was weakest. Some spurious interactions were also found, however. The method was also capable to identify interactions in the real data set. Conclusions: We conclude that boosted regression trees can be used to uncover complex interaction effects in epidemiological studies.

National Category
Probability Theory and Statistics Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-228915 (URN)10.1186/1476-069X-13-57 (DOI)000340001300001 ()24993424 (PubMedID)
Available from: 2014-07-22 Created: 2014-07-22 Last updated: 2017-12-05Bibliographically approved
3. Atherosclerosis in Humans and the Association to Environmental Contaminant Mixtures
Open this publication in new window or tab >>Atherosclerosis in Humans and the Association to Environmental Contaminant Mixtures
(English)Manuscript (preprint) (Other academic)
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-237688 (URN)
Available from: 2014-12-04 Created: 2014-12-04 Last updated: 2015-03-09
4. Mixture Effects of Multiple Environmental Contaminants on the Metabolic Syndrome in a Human Population-based Sample
Open this publication in new window or tab >>Mixture Effects of Multiple Environmental Contaminants on the Metabolic Syndrome in a Human Population-based Sample
(English)Manuscript (preprint) (Other academic)
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-237689 (URN)
Available from: 2014-12-04 Created: 2014-12-04 Last updated: 2015-03-09

Open Access in DiVA

fulltext(6642 kB)377 downloads
File information
File name FULLTEXT01.pdfFile size 6642 kBChecksum SHA-512
243d6215aeba0f531e5d69308fe8e8e2726d41ae106c374c40e2554f4e2ce2cea2fedbf85ac3ce8e62a5582ee862436676502253c85c2dfbe6ff9ebbdc3a727f
Type fulltextMimetype application/pdf
Buy this publication >>

Search in DiVA

By author/editor
Lampa, Erik
By organisation
Occupational and Environmental Medicine
Environmental Health and Occupational HealthProbability Theory and Statistics

Search outside of DiVA

GoogleGoogle Scholar
Total: 377 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 1376 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf