Exposure to Phthalate Mixtures and Inner-City Pediatric Allergic Disease and Airway Inflammation

Phthalate plasticizers are found in consumer products and home furnishing materials. Phthalate urinary metabolites are detected in nearly every sample in population-based studies indicating widespread exposure. Prior epidemiologic studies have associated vinyl flooring, a proxy for phthalate exposure, or house dust concentrations of phthalates with eczema and asthma in children. However, these studies lack adequate exposure measurements, consideration of the early life period, and prospective designs. In light of these gaps in the literature, we designed epidemiologic analyses to address our overarching hypothesis that early life exposure to a mixture of phthalates will have associations with adverse allergic and respiratory health outcomes in children. We tested this hypothesis in five self-contained manuscripts that characterize sources of exposure to phthalates in early life, demonstrate the application of new statistical methods for estimating effects of these highly correlated biomarkers, and test the association between early life exposure to phthalates and eczema and airway inflammation in children. Participants were enrolled from the longitudinal birth cohort of the Columbia Center for Children's Environmental Health (CCCEH) in New York City. Phthalate metabolites were measured in prenatal and child urine samples at the Centers for Disease Control and Prevention. Questionnaires and visual inspections were combined with phthalate measurements from personal and indoor air sampling and urinary metabolite concentrations to examine sources and patterns of phthalate exposure associated with personal care product use and flooring materials in the home. The use of perfume and personal care products was associated with higher exposure to the metabolite of diethyl phthalate (DEP) but not di-n-butyl phthalate (DnBP). Vinyl flooring in the home was associated with higher indoor air and urinary metabolite concentrations for butylbenzyl phthalate (BBzP) but not di(2-ethylhexyl) phthalate (DEHP). Because some phthalates share exposure sources and have multiple metabolites, the urinary biomarker concentrations can be highly correlated. Using a reanalysis of the association between prenatal phthalate metabolites and reduced gestational age, we demonstrate that simple Bayesian models can estimate effects for highly correlated exposure measures without the instability of conventional modeling approaches. We found that prenatal concentrations of the metabolite of butylbenzyl phthalate were associated with the report of early-eczema but not atopy among children in the cohort. In a cross-sectional analysis, children's urinary concentrations of metabolites of diethyl phthalate and butylbenzyl phthalate were both associated with higher fractional exhaled nitric oxide, a marker of airway inflammation. These findings suggest several important sources of exposure to phthalates and demonstrate new methods for highly correlated exposures that have not been widely applied in the environmental health sciences. The association of biomarkers of exposure to butylbenzyl phthalate and eczema extend the findings of previous studies. Our results include the first report of an association between phthalates and airway inflammation in children.