Infants and young children spend more than 95% of their time indoors where they receive chronic exposures to semi-volatile organic compounds (SVOCs) from contact with indoor dust due to their increased hand to mouth activity and crawling behavior. Several SVOCs commonly detected in indoor dust are considered "chemical obesogens", which are defined as chemicals that alter lipid homeostasis and fat storage, alter metabolic set points, or disrupt energy balance, resulting in fat accumulation and obesity. Several recent studies have suggested that perinatal exposure to obesogens may result in increased odds of obesity in children. Current research also suggests that many of these chemicals compounds act via a mechanism that includes activation of peroxisome proliferator-activated nuclear receptors (PPARs), leading to adipogenesis. Our preliminary studies demonstrate that rats prenatally exposed to an environmentally relevant dust mixture were heavier at birth, and throughout their life. Current approaches to measuring children's exposure to chemicals present in dust have typically relied on simplistic and crude dust ingestion rates, or measurements in serum or urine, the latter being expensive and typically isolated to one or few specific chemicals. Therefore, there is a critical need to provide better estimates of integrated exposure to SVOC mixtures and validate appropriate exposure markers. Given the chronic and sometimes high SVOC exposure that occurs in some homes, we hypothesize that early life exposure to mixtures of SVOCs in indoor dust leads to increased odds of obesity in children, and that these effects are associated primarily with chemicals in dust having high PPAR? and adipogenic activity. To address this hypothesis we have recruited a multi-disciplinary team that will leverage the resources of, and collaborate with, an ongoing NIH funded birth cohort examining associations between prenatal nutrition, secondhand tobacco smoke, and epigenetics modifications on obesity in children. We will conduct a nested case control study with 100 overweight/obese and 100 non-obese toddlers and quantify their prenatal and postnatal exposure to mixtures of SVOCs using targeted and non-targeted (e.g. screening) approaches. House dust samples will be characterized for both adipogenic and PPAR activity using in vitro assays, which will provide greater insight into effects related to actual exposure t dust particles. Associations between obesity (and other health outcomes available in the study), contaminant exposure (individual chemicals and mixtures) and adipogenic/PPAR? activity in dust samples will be examined. This work will contribute new data regarding the potential health impacts from pre- and postnatal exposure to contaminant mixtures present in house dust, and help identify mitigating factors.

Public Health Relevance

Obesity rates in the US, particularly in toddlers, are rapidly climbing and it has been hypothesized that early life exposure to chemicals which act as obesogens may be a contributing factor. The goal of this research is to examine the associations between perinatal exposures to mixtures of SVOCs present in house dust, adipogenic potential of house dust, and obesity outcomes in toddlers. We will also explore the use of handwipes as an improved measure of SVOC exposure in the home environment using both targeted and non- targeted (i.e. screening) approaches to characterize exposure to mixtures of SVOCs. This work will contribute new data regarding the potential health impacts in children from chronic exposure to contaminants present in house dust, and help identify mitigating factors.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
2R01ES016099-06A1
Application #
8761391
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Gray, Kimberly A
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Duke University
Department
None
Type
Earth Sciences/Resources
DUNS #
City
Durham
State
NC
Country
United States
Zip Code
27705
Hoffman, Kate; Fang, Mingliang; Horman, Brian et al. (2014) Urinary tetrabromobenzoic acid (TBBA) as a biomarker of exposure to the flame retardant mixture Firemaster® 550. Environ Health Perspect 122:963-9
Noyes, Pamela D; Lema, Sean C; Roberts, Simon C et al. (2014) Rapid method for the measurement of circulating thyroid hormones in low volumes of teleost fish plasma by LC-ESI/MS/MS. Anal Bioanal Chem 406:715-26
Dishaw, Laura V; Macaulay, Laura J; Roberts, Simon C et al. (2014) Exposures, mechanisms, and impacts of endocrine-active flame retardants. Curr Opin Pharmacol 19:125-33
Pillai, Hari K; Fang, Mingliang; Beglov, Dmitri et al. (2014) Ligand binding and activation of PPAR? by Firemaster® 550: effects on adipogenesis and osteogenesis in vitro. Environ Health Perspect 122:1225-32
Muzzio, Amanda M; Noyes, Pamela D; Stapleton, Heather M et al. (2014) Tissue distribution and thyroid hormone effects on mRNA abundance for membrane transporters Mct8, Mct10, and organic anion-transporting polypeptides (Oatps) in a teleost fish. Comp Biochem Physiol A Mol Integr Physiol 167:77-89
Stapleton, Heather M; Misenheimer, John; Hoffman, Kate et al. (2014) Flame retardant associations between children's handwipes and house dust. Chemosphere 116:54-60
Dong, Wu; Macaulay, Laura J; Kwok, Kevin W H et al. (2013) Using whole mount in situ hybridization to examine thyroid hormone deiodinase expression in embryonic and larval zebrafish: a tool for examining OH-BDE toxicity to early life stages. Aquat Toxicol 132-133:190-9
Carignan, Courtney C; McClean, Michael D; Cooper, Ellen M et al. (2013) Predictors of tris(1,3-dichloro-2-propyl) phosphate metabolite in the urine of office workers. Environ Int 55:56-61
Noyes, Pamela D; Lema, Sean C; Macaulay, Laura J et al. (2013) Low level exposure to the flame retardant BDE-209 reduces thyroid hormone levels and disrupts thyroid signaling in fathead minnows. Environ Sci Technol 47:10012-21
Meeker, John D; Cooper, Ellen M; Stapleton, Heather M et al. (2013) Urinary metabolites of organophosphate flame retardants: temporal variability and correlations with house dust concentrations. Environ Health Perspect 121:580-5

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