Phthalates and Adaptive Immune Response: Role of Social and Biological Factors in Exposure and Vulnerability

People are exposed to numerous chemicals daily through the products we use, the food we eat, and the air we breathe. This has been demonstrated by research that indicates virtually all people living in the industrialized world have numerous chemicals in their blood, which has led to growing scientific and public concern over the potential health implications of these exposures. Chemicals, such as phthalates, are a significant public health concern because decades of research have linked them to a wide range of health effects. This dissertation contributes to the literature by assessing how sociodemographic factors influence exposure to phthalate metabolites (Paper 1), and how exposures to phthalates individually (Paper 2) and in combination (Paper 3) affect antibody concentrations (i.e. titers) against organisms that cause infectious diseases. This dissertation utilized data from five cross-sectional cycles of the National Health and Nutrition Examination Survey, a nationally representative sample of U.S. residents one year and old, to prepare three dissertation papers. The first paper assessed how sociodemographic characteristics influenced exposure distributions with a focus on birthplace, age, and sex/gender differences. This study found that overall phthalate exposure has decreased for most metabolites examined between 2003 and 2012. While exposure to phthalates was ubiquitous, foreign-born persons generally had greater exposure compared to U.S.-born persons, particularly for low molecular weight (LMW) metabolites; males typically had greater risk of exposure to high molecular weight (HMW) phthalates; and young persons had greater overall exposure compared to adults. The second paper tested associations between single phthalate metabolite and individual antibody measures against measles virus, mumps virus, rubella virus, poliovirus, Epstein-Bar virus, and Toxoplasma gondii. When examining the association between single metabolites and individual antibody measures, exposure to LMW phthalates was generally positively associated with measles, poliovirus, and Epstein-Barr virus antibodies, respectively. Conversely, HMW phthalates were inversely associated with both rubella and poliovirus antibodies. Males typically experienced immune enhancement while suppression was primarily observed in females.Lastly, the third paper evaluated how co-exposures to phthalate influenced multiple antibody titers simultaneously. This was accomplished with structural equation modeling that showed LMW phthalate metabolites were associated with immune enhancement while HMW phthalates were associated with immune suppression with the exception of mono-ethyl phthalate. If associations are causal, exposure to HMW phthalates could increase a person’s risk to infectious diseases while exposure to LMW phthalates could be immunoprotective, or they could increase susceptibility to autoimmunity and/or allergy