|Abstract or Summary
- The human health effects of exposure to numerous single environmental contaminants have been well characterized. Yet, biomonitoring studies have detected multiple environmental chemicals in humans, highlighting the need to investigate the health effects of exposure to multiple environmental chemicals. Environmental data is highly complex, therefore current methods of defining environmental mixtures and examining relationships between exposure and health outcomes often do not capture the dynamic relationship between chemicals or take into account different modes of action. The introduction contextualizes the limitations in defining environmental mixtures and outlines the need for understanding the relationship between exposure to environmental mixtures and important health outcomes. Recursive partition mixture modelling (RPMM) was used to evaluate the US population’s exposure to mixtures of environmental chemicals. Path analysis and structural equation modeling (SEM) were used to evaluate the relationship between exposure to environmental mixtures and cognitive functioning and thyroid hormone disruption, respectively.
The objective of the study presented in chapter 2 was to develop a novel approach to identify exposure profiles of 7 common environmental chemicals in a US population. This study provides evidence the US population has 8 mixture profiles of 7 environmental chemicals (lead, cadmium, bisphenol-A (BPA), triclosan, benzophenone-3, 2,4-dichlorophenol, and 2,5-dichlorophenol). The findings also showed that different subpopulations in the US are exposed to different mixture profiles. Specifically, Non-Hispanic Black (NHB) or Other Hispanic (OH) males below the poverty index threshold were most likely to have the highest exposure. This study built on previous definitions of environmental mixtures by using biomarkers of exposure to report the dynamic relationship between chemicals of different classes and modes of actions.
The third chapter evaluated the relationship between exposure to a mixture of neurotoxins (lead, cadmium, 8 non-dioxin-like PCBs, and 4 dioxin like PCBs) and cognitive functioning in older US adults. The results indicate that lead and non-dioxin like PCBs, specifically PCB 146 has a negative relationship with cognitive functioning. This study confirmed that lead is negatively associated with cognitive functioning when controlling for exposure to other neurotoxin. Unlike previous studies using the same dataset that used an additive definition of PCBs mixtures it was found that non-dioxin-like PCBs were negatively associated with cognitive functioning, signifying different conclusion may be reached based on the definition of environmental mixtures.
The fourth chapter evaluated the association between exposure to a mixture of 11 endocrine disrupting compounds (EDCs) (7 phthalates, 3 phenols, and perchlorate), thyroid hormones (THs), and body mass index (BMI). We observed that exposure to multiple EDCs was associated with thyroid functioning in both males and females. A positive association between exposure to multiple EDCs and BMI directed through alterations in concentrations of thyroid stimulating hormone (TSH) was observed in females only. These results confirm that women may be more susceptible to higher BMI from exposure to individual EDCs, but is the first to suggest higher BMI is a result of TH alterations from exposure to multiple EDCs
The fifth chapter provides a summary and conclusions of the 3 studies. In addition to describing a more realistic environmental mixture exposure scenario in US subpopulations, these results provide evidence that exposure to multiple environmental chemicals is detrimental to important human health outcomes. Future studies should focus on incorporating a greater number of chemicals with different modes of action into environmental mixture profiles and use these profiles to direct future toxicology and epidemiology studies. Public health interventions, policies, and regulations can protect human health from the detrimental effects of environmental exposures by focusing on reducing exposure to common co-exposures or chemicals known to have synergistic effects. Overall, these results can guide future toxicology and epidemiology research into the health effects related to multiple environmental exposures.