Association of Urinary Phthalates with Self-Reported Eye Affliction/Retinopathy in Individuals with Diabetes: National Health and Nutrition Examination Survey, 2001-2010.
ABSTRACT: Background. An epidemiological association between exposure to phthalates and type 2 diabetes (T2D) is known. However, the potential role of environmental phthalates in the complications of T2D is unknown. Methods. Using data from the National Health and Nutrition Examination Survey (NHANES) 2001-2010, we studied the association of 12 urinary phthalate metabolites with self-reported eye affliction/retinopathy in 1,004 participants with diabetes. Data from retinal imaging was used to validate this outcome. Independence of the phthalates?T2D association was studied by adjusting for age, sex, race, marital status, educational attainment, poverty income ratio, physical activity, glycated hemoglobin levels, total serum cholesterol, serum high-density lipoprotein cholesterol, serum triglycerides, blood pressure, duration of diabetes, total calorie intake, and obesity. Results. Self-reported eye affliction/retinopathy had 82% accuracy with Cohen's kappa of 0.31 (p < 0.001). Urinary mono-n-octyl phthalate (MOP) was independently associated with the likelihood of self-reported eye affliction/retinopathy in subjects with T2D after accounting for all the confounders. This significance of this association was robust to the potential misclassification in cases and controls of retinopathy. Further, a significant dose-response relationship between MOP and self-reported eye affliction/retinopathy was demonstrable. Conclusions. We show a novel epidemiological link between the environment and diabetic complications in NHANES 2001-2010 participants.
Project description:Environmental exposure to phthalates may contribute to an increased risk of asthma in children and adults. We aimed to assess the direction and strength of the association between urinary phthalates metabolites and current asthma in children and adults that participated in the National Health and Nutrition Examination Survey (NHANES) 2007-2012. Data on ten urinary phthalate metabolites, self-reported questionnaires, spirometry measures, and covariates were obtained from 7765 participants (28.1% were children aged 6-17 years) taking part in the NHANES 2007-2012. Asthma was assessed using self-reported questionnaires for children and adults, and via spirometry measures for adults alone. We used crude and adjusted logistic regression models to estimate the odds ratios (ORs) and 95% confidence interval (CI) per one log10 unit change in the concentration of phthalate metabolites. We further modeled the effect modification by sex. Out of 10 metabolites, only mono-benzyl phthalate (MBzP) was positively associated with the prevalence of self-reported asthma in children, after adjusting for a range of potential confounders (odds ratio 1.54; 95% confidence interval 1.05-2.27). No significant relationship was observed for adults. The association of mono-ethyl phthalate (MEP) was modified by sex, with significantly increased odds of asthma among males [boys (2.00; 1.14-3.51); adult males (1.32; 1.04-1.69)]. While no other phthalates showed a positive relationship with current asthma in males, mono-(carboxynonyl) phthalate (MCNP) and mono-(3-carboxylpropyl) phthalate (MCPP) were inversely associated with spirometrically defined asthma in adult females. A sex-specific relationship in adults was evident when spirometry, but not self-reported measures were used to define asthma. We found no clear association between exposure to phthalates and current asthma, except for a significant relationship between MBzP metabolites and self-reported asthma in children. As a result, exposure to phthalates and asthma development and/or exacerbations remains controversial, suggesting a need for a well-designed longitudinal study.
Project description:As regulatory initiatives increasingly call for an understanding of the cumulative risks from chemical mixtures, evaluating exposure data from large biomonitoring programs, which may inform these cumulative risk assessments, will improve the understanding of occurrence and patterns of coexposures. Here we have analyzed the urinary metabolite data for six phthalates (di-butyl phthalate; di-isobutyl phthalate; butyl-benzyl phthalate; bis(2-ethylhexyl) phthalate; di-isononyl phthalate; and di-isodecyl phthalate) in the 2007/2008 National Health and Nutrition Examination Survey (NHANES) data set. For the total data set (N=2604), the co-occurrence of multiple phthalates at the upper percentile of exposure was infrequent. There were no individuals in the NHANES sample who were exposed to >95th percentiles for all six phthalates. For 75% of individuals, none of the six phthalates were above the 95th percentile of their respective exposure distributions. These data suggest that high exposure to multiple phthalates is infrequent in the NHANES population. This analysis solely focused on the pattern of contribution of individual phthalates to total exposure. It did not address the pattern of contribution to potential risk. The approach presented could potentially be used to provide insight into understanding the coexposure patterns for other chemicals.
Project description:The Maximum Cumulative Ratio (MCR) quantifies the degree to which a single chemical drives the cumulative risk of an individual exposed to multiple chemicals. Phthalates are a class of chemicals with ubiquitous exposures in the general population that have the potential to cause adverse health effects in humans. This work used the MCR to evaluate coexposures to six phthalates as measured in biomonitoring data from the most recent cycle (2013-2014) of the National Health and Nutrition Examination Survey (NHANES). The values of MCR, Hazard Index (HI), and phthalate-specific Hazard Quotients (HQs) were determined for 2663 NHANES participants aged six years and older by using reverse dosimetry techniques to calculate steady-state doses consistent with concentrations of metabolites of six phthalates in urine and using Tolerable Daily Intake values. There were 21 participants (0.8% of the NHANES sample) with HI>1. Of those, 43% (9/21) would have been missed by chemical-by-chemical assessments (i.e. all HQs were less than one). The mean MCR value in the 21 participants was 2.1. HI and MCR values were negatively correlated (p<0.001) indicating that most participants, especially those with elevated HI values, had their cumulative risks driven by relatively large doses of a single phthalate rather than doses of multiple phthalates. The dominate phthalate varied across participants. Children (aged 6-17years) had a higher HI values (p<0.01) than adults (18+ years). However, the probability of having HI>1 was not driven by age, gender, or ethnicity. The cumulative exposures of concern largely originated from a subset of three of the fifteen possible pairs of the six phthalates. These findings suggest that cumulative exposures were a potential concern for a small portion of the surveyed participants involving a subset of the phthalates explored. The largest risks tended to occur in individuals whose exposures were dominated by a single phthalate.
Project description:Prospective evidence regarding associations for exposures to bisphenol A (BPA) and phthalates with type 2 diabetes (T2D) is lacking.We prospectively examined urinary concentrations of BPA and phthalate metabolites with T2D risk.We measured BPA and eight major phthalate metabolites among 971 incident T2D case-control pairs from the Nurses' Health Study (NHS) (mean age, 65.6 years) and NHSII (mean age, 45.6 years).In the NHSII, BPA levels were not associated with incident T2D in multivariate-adjusted analysis until body mass index was adjusted: odds ratio (OR) comparing extreme BPA quartiles increased from 1.40 (95% CI: 0.91, 2.15) to 2.08 (95% CI: 1.17, 3.69; p(trend) = 0.02) with such an adjustment. In contrast, BPA concentrations were not associated with T2D in the NHS (OR = 0.81; 95% CI: 0.48, 1.38; p(trend) = 0.45). Likewise, urinary concentrations of total phthalate metabolites were associated with T2D in the NHSII (OR comparing extreme quartiles = 2.14; 95% CI: 1.19, 3.85; p(trend) = 0.02), but not in the NHS (OR = 0.87; 95% CI: 0.49, 1.53; p(trend) = 0.29). Summed metabolites of butyl phthalates or di-(2-ethylhexyl) phthalates were significantly associated with T2D only in the NHSII; ORs comparing extreme quartiles were 3.16 (95% CI: 1.68, 5.95; p(trend) = 0.0002) and 1.91 (95% CI: 1.04, 3.49; p(trend) = 0.20), respectively.These results suggest that BPA and phthalate exposures may be associated with the risk of T2D among middle-aged, but not older, women. The divergent findings between the two cohorts might be explained by menopausal status or simply by chance. Clearly, these results need to be interpreted with caution and should be replicated in future studies, ideally with multiple urine samples collected prospectively to improve the measurement of these exposures with short half-lives.
Project description:General population human biomonitoring programs such as the National Health and Nutrition Examination Survey (NHANES) in the United States suggest that chemical exposures are common. Exposures during childhood may affect health later in life, but biomonitoring data in NHANES among pre-school aged children are limited.A convenience group of 122 3-5year old American boys and girls were recruited in 2013 for a pilot study to assess the feasibility of collecting urine from young children and analyzing it for select chemical exposure biomarkers for future NHANES. Children were primarily Hispanic (64.8%); the remainder was divided between non-Hispanic black, and non-Hispanic white and "other." We measured 52 urinary biomarkers: 13 phthalates and one non-phthalate plasticizer, five phenols and four parabens, 10 polycyclic aromatic hydrocarbons (PAHs), and 19 pesticides. For each biomarker, we calculated descriptive statistics. We also calculated the number of biomarkers detected within each child, and performed principal components analysis (PCA).NHANES staff obtained permission to attempt collection of 60mL urine from 3 to 5year olds who participated in the 2013 NHANES health examination; 83% of children successfully provided the target volume. We detected 24 individual biomarkers of pesticides, phenols and parabens, phthalates/non-phthalate plasticizers, and PAHs in 95-100% of children. The median number of biomarkers detected was 37: nine pesticides, five phenols and parabens, 13 phthalates and non-phthalate plasticizers, and 10 PAHs. Biomarkers concentrations appear to be similar to national estimates among 6-11year old children from previous NHANES. PCA suggested high within-class correlations among biomarkers.These young children successfully adhered to the collection protocol and produced enough urine for the quantification of environmental biomarkers currently being measured in NHANES participants 6 years of age and older. Using the same analytical methods employed for the analysis of samples collected from older NHANES participants, in this sample of pre-school aged children we detected multiple chemicals including plasticizers, combustion products, personal-care product chemicals, and pesticides. Starting with NHANES 2015-2016, the NHANES biomonitoring program will include urinary biomarkers for 3-5year old children to provide exposure data to select chemicals at the national level among this age group.
Project description:BACKGROUND:Research suggests that dietary supplements may be a source of exposure to phthalates, given that diethyl phthalate (DEP) or di-n-butyl phthalate (DBP) can be components of coatings that facilitate extended release or encapsulate dietary supplements. METHODS:Using nationally representative data on a population of 12,281 adults ages 20?y?+?surveyed between 1999 and 2014 from the National Health and Nutrition Examination Survey (NHANES), we evaluated the association between dietary supplement use in relation to urinary phthalate metabolites of DEP (monoethyl phthalate, MEP) and DBP (mono-n-butyl phthalate, MBP). We examined associations pertaining to regular use of multivitamin/multimineral (MVMM) supplements, as well as regular use of any other non-MVMM supplement products, the number of non-MVMM supplement products used, as well as individual supplements potentially containing phthalates (exclusive of MVMM). For each urinary phthalate metabolite, results are presented as the minimally-adjusted and multivariable-adjusted ratio, comparing the geometric mean among users to non-users. RESULTS:In multivariable models, we observed a significant positive association between regular use of MVMM use and MEP, with persons using MVMM supplements having 11% higher geometric mean MEP than non-users (Ratio: 1.11; 95% CI: 1.04-1.20); no association was observed for MVMM in relation to MBP. No other significant multivariable-adjusted associations were observed, although power was limited in analyses of individual supplements. Associations did not markedly vary by gender; however, the associations of garlic supplement use with MEP and MBP varied by calendar time, with statistically significant positive associations observed in later years. CONCLUSIONS:A modest significant association was observed between MVMM use and MEP. No other significant associations were observed in our overall multivariable models. Follow-up on the positive association observed between garlic and urinary phthalate metabolite concentrations observed in later years in a well-powered, prospective study would further clarify study findings.
Project description:Environmental exposures to phthalates, particularly high-molecular-weight (HMW) phthalates, are suspected to contribute to allergy.We assessed whether phthalate metabolites are associated with allergic symptoms and sensitization in a large nationally representative sample.We used data on urinary phthalate metabolites and allergic symptoms (hay fever, rhinitis, allergy, wheeze, asthma) and sensitization from participants ? 6 years of age in the National Health and Nutrition Examination Survey (NHANES) 2005-2006. Allergen sensitization was defined as a positive response to at least one of 19 specific IgE antigens (? 0.35 kU/L). Odds ratios (ORs) per one log10 unit change in phthalate concentration were estimated using logistic regression adjusting for age, race, body mass index, gender, creatinine, and cotinine. Separate analyses were conducted for children (6-17 years of age) and adults.The HMW phthalate metabolite monobenzyl phthalate (MBzP) was the only metabolite positively associated with current allergic symptoms in adults (wheeze, asthma, hay fever, and rhinitis). Mono-(3-carboxypropyl) phthalate and the sum of diethylhexyl phthalate metabolites (both representing HMW phthalate exposures) were positively associated with allergic sensitization in adults. Conversely, in children, HMW phthalate metabolites were inversely associated with asthma and hay fever. Of the low-molecular-weight phthalate metabolites, monoethyl phthalate was inversely associated with allergic sensitization in adults (OR = 0.79; 95% CI: 0.70, 0.90).In this cross-sectional analysis of a nationally representative sample, HMW phthalate metabolites, particularly MBzP, were positively associated with allergic symptoms and sensitization in adults, but there was no strong evidence for associations between phthalates and allergy in children 6-17 years of age.
Project description:Phthalates are chemical esters used as additives in common consumer goods, such as plastics, household cleaners, and personal care products. Phthalates are not chemically bound to the items to which they are added and can easily leach into the surrounding environment. Anthropogenic drivers, such as coastal plastic pollution and wastewater runoff, increase the exposure potential for coastal marine fauna. Phthalate exposure in free-ranging bottlenose dolphins has been the focus of recent study, with indications of heightened exposure to certain phthalate compounds. The objective of this study was to compare urinary phthalate metabolite concentrations among bottlenose dolphins (Tursiops truncatus) sampled in Sarasota Bay, FL, to levels reported in human samples collected as part of the Centers for Disease Control and Prevention's (CDC) National Health and Nutrition Examination Survey (NHANES). Monoethyl phthalate (MEP) and mono-(2-ethylhexyl) phthalate (MEHP) were the most prevalent metabolites detected in dolphin urine (n = 51; MEP = 29.41%; MEHP = 54.90%). The geometric mean (GM) concentration of MEP was significantly lower for dolphins (GM = 4.51 ng/mL; 95% CI: 2.77-7.34 ng/mL) compared to humans (p<0.05), while dolphin concentrations of MEHP (GM = 4.57 ng/mL; 95% CI: 2.37-8.80 ng/mL) were significantly higher than levels reported in NHANES (p<0.05). Health impacts to bottlenose dolphins resulting from elevated exposure to the MEHP parent compound (diethyl-2-ethylhexyl phthalate, DEHP) are currently unknown. However, given the evidence of endocrine disruption, reproductive impairment, and abnormal development in humans, pursuing investigations of potential health effects in exposed bottlenose dolphins would be warranted.
Project description:Phthalate exposure has been associated with a wide range of adverse health outcomes in limited epidemiologic studies, and inflammation and oxidative stress have been hypothesized as potential mechanisms involved. In the present study we investigated associations between urinary concentrations of phthalate metabolites and potential blood markers of oxidative stress (bilirubin) and inflammation (alkaline phosphatase [ALP], absolute neutrophil count [ANC], ferritin [adjusted for iron status], and fibrinogen), using data from 10,026 participants in the National Health and Nutrition Examination Survey (NHANES) recruited between 1999 and 2006. After adjustment for covariates we found that bilirubin was inversely associated with several phthalate metabolites (all p-values <0.0001), including the metabolites of di-2-ethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP), in addition to monobenzyl phthalate (MBzP) and mono-(3-carboxypropyl) phthalate (MCPP). Since bilirubin is a potent antioxidant these relationships suggest that phthalates may be associated with increased oxidative stress. Many of the same metabolites were also significantly and positively related with ANC, ALP, and ferritin, suggesting phthalates may be associated with increased inflammation. These markers may be useful in other studies of low-dose exposure to environmental contaminants.
Project description: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.