Exposure to Chemical Mixtures and Associated Health Risks: Focusing on Endocrine Disruption and the Swedish General Population
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]
Humans are exposed to a wide range of environmental pollutants through multiple routes of exposure. Chemical exposure can result in endocrine-disrupting effects, manifesting at low concentrations, and are associated with several health problems, such as infertility, obesity, and autoimmune diseases. This thesis aims to evaluate the potential health effects of exposure to complex chemical mixtures. Two key objectives were to understand human chemical exposure and investigate whether the Swedish general population falls within the risk threshold for health effects related to this exposure. In Paper I, a literature review was conducted to investigate chemical exposure based on existing knowledge, compiling peer-reviewed literature on chemicals and their exposure levels in Swedish human blood. Additional chemicals were analyzed in Swedish human blood to examine exposure to chemicals currently used, such as per- and polyfluoroalkyl substances (PFAS, Paper II) and synthetic phenolic contaminants (Paper III). A 50-component chemical mixture was created based on human blood levels found in Papers I-III to better understand the potential endocrine-disrupting and developmental toxic effects. Persistent organic pollutants (POPs) were the most frequently studied and detected chemicals analyzed in human blood (Paper I), prompting the inclusion of four POP classes in the artificial mixture. New contaminants not previously found in Swedish samples were also identified, including hydrogen-substituted perfluoroalkyl carboxylic acids (Paper II) and synthetic phenolic antioxidants (SPAs) (Paper III). Some PFAS and SPAs were present in all individuals at high levels, motivating the addition of the SPAs into the chemical mixture. Mixture risk assessment strategies were employed to evaluate the potential adverse effects of exposure to POPs (Paper I) and PFAS (Paper II). The mixture comprises polychlorinated biphenyls (PCBs), brominated flame retardants, organochlorine pesticides, PFAS, SPAs, bisphenol A, and phthalates. The total mixture was tested as a whole and as six subgroup mixtures to identify the drivers of effect. The mixtures were evaluated using in vitro cell assays to screen for binding to estrogen receptor α, androgen receptor, and aryl hydrocarbon receptor (Paper IV). The developmental toxicity of the mixtures was examined using the zebrafish embryo toxicity (ZFET) test (Paper V). The effects associated with exposure to the total chemical mixture demonstrated estrogen and androgen activity at 10 and 15 times human blood concentration (xHBC), respectively, levels that fall within the human blood exposure range of the Swedish general population (Paper IV). Developmental effects were observed at 15 xHBC using the ZFET test (Paper V). This thesis identified that POPs, such as PFAS, chlorinated pesticides, and PCBs, continue to pose a health threat. Newly identified SPAs present a potential risk due to high exposure levels and need further investigation. The mixture risk assessment strategies employed in this thesis suggest that a risk of health impairments from known chemical exposure cannot be ruled out for the Swedish population. Although these risk assessments are only tentative, they add to the ever-growing body of evidence, showing that mixtures pose an unavoidable health concern to humans. Therefore, it is essential to manage and limit human exposure to the mixture of environmental pollutants to ensure the well-being of future generations.
Place, publisher, year, edition, pages
Stockholm: Department of Environmental Science, Stockholm University , 2025. , p. 73
Keywords [en]
Chemical mixtures, Human blood, Chemical exposure, Sweden, Human health, Synthetic phenolic antioxidants (SPAs), PFAS, Persistent organic pollutants, Mixture risk assessments, Endocrine disruption, in vitro, zebrafish embryo toxicity (ZFET) test
National Category
Environmental Sciences Analytical Chemistry Occupational Health and Environmental Health
Research subject
Environmental Sciences
Identifiers
URN: urn:nbn:se:su:diva-239371ISBN: 978-91-8107-114-6 (print)ISBN: 978-91-8107-115-3 (electronic)OAI: oai:DiVA.org:su-239371DiVA, id: diva2:1936583
Public defence
2025-03-28, De Geer-salen, Geovetenskapens hus, Svante Arrhenius väg 14 and online via Zoom, public link is available at the department website, Stockholm, 10:00 (English)
Opponent
Supervisors
Funder
Swedish Research Council Formas, 2018-022642025-03-052025-02-112025-02-21Bibliographically approved
List of papers