Susanna D. Mitro

Recent Fast Food Consumption and Bisphenol A and Phthalates Exposures among the U.S. Population in NHANES, 2003-2010.

Background: Phthalates and bisphenol A (BPA) are widely used industrial chemicals that may adversely impact human health. Human exposure is ubiquitous and can occur through diet, including consumption of processed or packaged food. Objective: To examine associations between recent fast food intake and BPA and urinary metabolites of di(2-ethylhexyl) phthalate (ΣDEHPm) and diisononyl phthalate (DiNPm) among the U.S. population. Methods: We combined data on 8,877 participants from the National Health and Nutrition Examination Survey (NHANES 2003–2010). Using 24-hr dietary recall data, we quantified: a) fast food intake [percent of total energy intake (TEI) from fast food]; b) fast food-derived fat intake (percent of TEI from fat in fast food); and c) fast food intake by food group (dairy, eggs, grains, meat, and other). We examined associations between dietary exposures and urinary chemical concentrations using multivariate linear regression. Results: We observed evidence of a positive, dose–response relationship between fast food intake and exposure to phthalates (p-trend < 0.0001) but not BPA; participants with high consumption (≥ 34.9% TEI from fast food) had 23.8% (95% CI: 11.9%, 36.9%) and 39.0% (95% CI: 21.9%, 58.5%) higher levels of ΣDEHPm and DiNPm, respectively, than nonconsumers. Fast food-derived fat intake was also positively associated with ΣDEHPm and DiNPm (p-trend < 0.0001). After adjusting for other food groups, ΣDEHPm was associated with grain and other intake, and DiNPm was associated with meat and grain intake. Conclusion: Fast food may be a source of exposure to DEHP and DiNP. These results, if confirmed, could inform individual and regulatory exposure reduction strategies. Citation: Zota AR, Phillips CA, Mitro SD. 2016. Recent fast food consumption and bisphenol A and phthalates exposures among the U.S. population in NHANES, 2003–2010. Environ Health Perspect 124:1521–1528; http://dx.doi.org/10.1289/ehp.1510803

Consumer Product Chemicals in Indoor Dust: A Quantitative Meta-analysis of U.S. Studies.

Indoor dust is a reservoir for commercial consumer product chemicals, including many compounds with known or suspected health effects. However, most dust exposure studies measure few chemicals in small samples. We systematically searched the U.S. indoor dust literature on phthalates, replacement flame retardants (RFRs), perfluoroalkyl substances (PFASs), synthetic fragrances, and environmental phenols and estimated pooled geometric means (GMs) and 95% confidence intervals for 45 chemicals measured in ≥3 data sets. In order to rank and contextualize these results, we used the pooled GMs to calculate residential intake from dust ingestion, inhalation, and dermal uptake from air, and then identified hazard traits from the Safer Consumer Products Candidate Chemical List. Our results indicate that U.S. indoor dust consistently contains chemicals from multiple classes. Phthalates occurred in the highest concentrations, followed by phenols, RFRs, fragrance, and PFASs. Several phthalates and RFRs had the highest residential intakes. We also found that many chemicals in dust share hazard traits such as reproductive and endocrine toxicity. We offer recommendations to maximize comparability of studies and advance indoor exposure science. This information is critical in shaping future exposure and health studies, especially related to cumulative exposures, and in providing evidence for intervention development and public policy.

Cumulative Chemical Exposures During Pregnancy and Early Development

Industrial and consumer product chemicals are widely used, leading to ubiquitous human exposure to the most common classes. Because these chemicals may affect developmental milestones, exposures in pregnant women and developing fetuses are of particular interest. In this review, we discuss the prevalence of chemical exposures in pregnant women, the chemical class-specific relationships between maternal and fetal exposures, and the major sources of exposures for six chemical classes of concern: phthalates, phenols, perfluorinated compounds (PFCs), flame retardants, polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCs). Additionally, we describe the current efforts to characterize cumulative exposures to synthetic chemicals during pregnancy. We conclude by highlighting gaps in the literature and discussing possible applications of the findings to reduce the prevalence of cumulative exposures during pregnancy.

Cross-Sectional Associations between Exposure to Persistent Organic Pollutants and Leukocyte Telomere Length among U.S. Adults in NHANES, 2001-2002.

Background: Exposure to persistent organic pollutants (POPs) such as dioxins, furans, and polychlorinated biphenyls (PCBs) may influence leukocyte telomere length (LTL), a biomarker associated with chronic disease. In vitro research suggests dioxins may bind to the aryl hydrocarbon receptor (AhR) and induce telomerase activity, which elongates LTL. However, few epidemiologic studies have investigated associations between POPs and LTL. Objectives: We examined the association between 18 PCBs, 7 dioxins, and 9 furans and LTL among 1,330 U.S. adults from NHANES 2001–2002. Methods: We created three summed POP metrics based on toxic equivalency factor (TEF), a potency measure including affinity for the AhR: a) non–dioxin-like PCBs (composed of 10 non–dioxin-like PCBs; no AhR affinity and no TEF); b) non-ortho PCBs (composed of 2 non–ortho-substituted PCBs with high TEFs); and c) toxic equivalency (TEQ) (composed of 7 dioxins, 9 furans, 2 non–ortho-substituted PCBs, and 6 mono–ortho-substituted PCBs; weighted by TEF). We tested the association between each metric and LTL using linear regression, adjusting for demographics, blood cell count and distribution, and another metric with a different TEF (i.e., non-ortho PCBs and TEQ adjusted for non–dioxin-like PCBs; non–dioxin-like PCBs adjusted for non-ortho PCBs). Results: In adjusted models, each doubling of serum concentrations of non-ortho PCBs and TEQ was associated with 3.74% (95% CI: 2.10, 5.40) and 5.29% (95% CI: 1.66, 9.05) longer LTLs, respectively. Compared with the lowest quartile, the highest quartile of exposure was associated with 9.16% (95% CI: 2.96, 15.73) and 7.84% (95% CI: –0.53, 16.92) longer LTLs, respectively. Non–dioxin-like PCBs were not associated with LTL. Conclusions: POPs with high TEFs and AhR affinity were associated with longer LTL. Because many dioxin-associated cancers are also associated with longer LTL, these results may provide insight into the mechanisms underlying PCB- and dioxin-related carcinogenesis. Citation: Mitro SD, Birnbaum LS, Needham BL, Zota AR. 2016. Cross-sectional associations between exposure to persistent organic pollutants and leukocyte telomere length among U.S. adults in NHANES, 2001–2002. Environ Health Perspect 124:651–658; http://dx.doi.org/10.1289/ehp.1510187

Vitamin D and uterine leiomyoma among a sample of US women: Findings from NHANES, 2001-2006.

Scientific understanding of the etiology of uterine leiomyomata (UL) remains incomplete, but recent investigations have suggested an association between low Vitamin D and UL risk. In this study, we conducted a cross-sectional analysis of Vitamin D exposure, measured using serum levels of 25(OH)D (a Vitamin D metabolite), and self-reported UL diagnosis among 3590 women aged 20-54 in the National Health and Nutrition Examination Survey (NHANES 2001-2006). Multivariate logistic regression models comparing each quartile of 25(OH)D to the lowest quartile indicated no relationship between 25(OH)D and odds of UL in the whole population (Ptrend=0.37), or in sensitivity analyses. However, a probabilistic analysis correcting outcome misclassification indicated that insufficient 25(OH)D was associated with UL in white (Odds ratio (OR) median estimate: 2.17; 2.5, 97.5 percentiles: (1.26, 23.47)), but not black women (OR median estimate: 1.70; 2.5, 97.5 percentiles: (0.89, 3.51)), suggesting misclassification may have driven some of the null findings.

Reducing chemical exposures at home: opportunities for action

Indoor environments can influence human environmental chemical exposures and, ultimately, public health. Furniture, electronics, personal care and cleaning products, floor coverings and other consumer products contain chemicals that can end up in the indoor air and settled dust. Consumer product chemicals such as phthalates, phenols, flame retardants and per- and polyfluorinated alkyl substances are widely detected in the US general population, including vulnerable populations, and are associated with adverse health effects such as reproductive and endocrine toxicity. We discuss the implications of our recent meta-analysis describing the patterns of chemical exposures and the ubiquity of multiple chemicals in indoor environments. To reduce the likelihood of exposures to these toxic chemicals, we then discuss approaches for exposure mitigation: targeting individual behaviour change, household maintenance and purchasing decisions, consumer advocacy and corporate responsibility in consumer markets, and regulatory action via state/federal policies. There is a need to further develop evidence-based strategies for chemical exposure reduction in each of these areas, given the multi-factorial nature of the problem. Further identifying those at greatest risk; understanding the individual, household and community factors that influence indoor chemical exposures; and developing options for mitigation may substantially improve individuals’ exposures and health.

Phthalate metabolite exposures among immigrants living in the United States: findings from NHANES, 1999–2014

Phthalates exposure has been linked to multiple health risks, and US immigrants may have different exposures to phthalates due to lifestyle differences. Urinary concentrations of eight phthalate metabolites (mono-ethyl phthalate [MEP], mono-n-butyl phthalate [MnBP], mono-isobutyl phthalate [MiBP], mono-(3-carboxypropyl) phthalate [MCPP], mono-benzyl phthalate [MBzP], mono-2-ethylhexyl phthalate [MEHP], mono-(2-ethyl-5-hydroxyhexyl) phthalate [MEHHP], mono-(2-ethyl-5-oxohexyl) phthalate [MEOHP]) were measured in 10318 US-born and 3511 foreign-born individuals from NHANES 1999–2014. Using multivariate adjusted linear regression, we assessed whether phthalate metabolite levels differed by nativity in the whole population, within racial/ethnic groups, and by years in the US. We also tested whether immigrant demographics predicted phthalate metabolite levels. In fully adjusted models, MEP, MnBP, and MiBP were significantly higher, and MBzP significantly lower, among immigrants than US-born participants. Among immigrants, MnBP and MiBP significantly declined with longer time in the US (Ptrend = 0.029 and Ptrend = 0.039, respectively), while MCPP and MBzP significantly rose (Ptrend = 0.019 and Ptrend = 0.043, respectively). Results within each racial/ethnic group were consistent with the whole population. Among immigrants, women had significantly higher metabolite levels than men (all p < 0.01), and MEP, MnBP, and MCPP differed by race/ethnicity. Due to higher phthalate exposures, immigrants may be especially vulnerable to phthalate-associated health problems.

Polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDE metabolites (OH-PBDEs) in maternal and fetal tissues, and associations with fetal cytochrome P450 gene expression

BACKGROUND Human fetal exposures to polybrominated diphenyl ethers (PBDEs) and their metabolites (OH-PBDEs) are unique from adults, and in combination with a different metabolic profile, may make fetal development more sensitive to adverse health outcomes from these exposures. However, we lack data to characterize human fetal PBDE exposures and the metabolic factors that can influence these exposures. OBJECTIVE We examined differences between 2nd trimester maternal and fetal exposures to PBDEs and OH-PBDEs. We also characterized fetal cytochrome P450 (CYP) mRNA expression and its associations with PBDE exposures. METHODS We collected paired samples of maternal serum and fetal liver (n=86) with a subset having matched placenta (n=50). We measured PBDEs, OH-PBDEs, and mRNA expression of CYP genes (e.g. CYP1A1, -2E1, -2J2, -2C9) in all samples. As a sensitivity analysis, we measured PBDEs and OH-PBDEs in umbilical cord serum from a subset (n=22). RESULTS BDE-47 was detected in ≥96% of all tissues. Unadjusted ∑PBDEs concentrations were highest in fetal liver (geometric mean (GM)=0.72ng/g), whereas lipid-adjusted concentrations were highest in cord serum (111.12ng/g lipid). In both cases, fetal concentrations were approximately two times higher than maternal serum levels (GM=0.33ng/g or 48.75ng/g lipid). ΣOH-PBDEs were highest in maternal and cord sera and 20-200 times lower than PBDE concentrations. In regression models, maternal BDE-47 explained more of the model variance of liver than of placenta BDE-47 concentrations (adjusted R2=0.79 vs 0.48, respectively). In adjusted logistic regression models, ∑PBDEs were positively associated with expression of CYP2E1 and -2J2 (placenta), and -1A1 (liver) (p<0.05). CONCLUSION Our findings suggest that under normal conditions of mid-gestation, the human fetus is directly exposed to concentrations of PBDEs that may be higher than previously estimated based on maternal serum and that these exposures are associated with the expression of mRNAs coding for CYP enzymes. These results will help frame and interpret findings from studies that use maternal or cord blood as proxy measures of fetal exposures, and will inform the molecular pathways by which PBDEs affect human health.