Associations of filaggrin gene loss-of-function variants with urinary phthalate metabolites and testicular function in young Danish Men.
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ABSTRACT:
SUBMITTER: Joensen UN
PROVIDER: S-EPMC3984221 | biostudies-other | 2014 Apr
REPOSITORIES: biostudies-other
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Associations of filaggrin gene loss-of-function variants with urinary phthalate metabolites and testicular function in young Danish Men.
Joensen Ulla Nordström UN Jørgensen Niels N Meldgaard Michael M Frederiksen Hanne H Andersson Anna-Maria AM Menné Torkil T Johansen Jeanne Duus JD Carlsen Berit Christina BC Stender Steen S Szecsi Pal Bela PB Skakkebæk Niels Erik NE Rajpert-De Meyts Ewa E Thyssen Jacob P JP
Environmental health perspectives 20140103 4
<h4>Background</h4>Filaggrin is an epidermal protein that is crucial for skin barrier function. Up to 10% of Europeans and 5% of Asians carry at least one null allele in the filaggrin gene (FLG). Reduced expression of filaggrin in carriers of the null allele is associated with facilitated transfer of allergens across the epidermis. We hypothesized that these individuals may have increased transdermal uptake of endocrine disruptors, including phthalates.<h4>Objectives</h4>We investigated urinary ...[more]
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Project description:Study questionAre urinary phthalate metabolites associated with reduced antral follicle growth among women in an infertility setting?Summary answerHigher urinary concentrations of di(2-ethylhexyl) phthalate (DEHP) metabolites were associated with significant decreases in antral follicle count (AFC) among women seeking infertility care.What is known alreadyExperimental animal studies show that DEHP accelerates primordial follicle recruitment and inhibits antral follicle growth. Whether phthalates also reduce the growing antral follicle pool in humans remains unknown.Study design, size, durationWe examined the association between urinary phthalate metabolites and AFC using prospective data from 215 females recruited between 2004 and 2012 in the Environment and Reproductive Health (EARTH) study.Participants/materials, setting, methodsWe quantified the urinary concentrations of 11 phthalate metabolites. We estimated the geometric mean for all urine samples provided prior to unstimulated day 3 AFC assessment for each woman. We evaluated the association of AFC with ∑DEHP (molar sum of four DEHP metabolites) and individual phthalate metabolites using Poisson regression, adjusting for age, BMI and smoking.Main results and the role of chanceWe observed significant decreases in mean AFC for all higher quartiles of ∑DEHP as compared with the lowest quartile. Compared with women in the first quartile of ∑DEHP, women in the second, third and fourth quartiles had a -24% (95% confidence interval (CI): -32%, -16%), -19% (95% CI: -27%, -9%), and -14% (95% CI: -23%, -5%) decrease in mean AFC. The absolute mean AFC in the first quartile was 14.2 follicles (95% CI: 13.2, 15.2) compared with 10.7 follicles (95% CI: 9.9, 11.6) in the second quartile. We observed similar trends among the four individual DEHP metabolites. There was no consistent change in AFC among the remaining phthalate metabolite concentrations evaluated.Limitations, reasons for cautionWe demonstrated a negative association between DEHP and a well-established marker of ovarian reserve among a subfertile population. However these findings may not be generalizable to women without fertility concerns, and we cannot rule out co-exposure to other chemicals.Wider implications of the findingsEnvironmental chemicals that inhibit the size of the growing antral follicle pool can impair fertility and reduce fecundity. This study suggests evidence in need of further investigation on the impact of phthalates on the human oocyte and follicular development.Study funding/competing interestsWork supported by grants ES009718, ES022955, ES000002, and T32ES007069 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32 DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). C.M. was supported by a post-doctoral training award from the Canadian Institutes of Health Research. There are no competing interests to declare.
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Project description:The variability and predictors of urinary concentrations of phthalate metabolites in preschool-aged children have not been thoroughly examined. Additionally, the impact of temporal changes in the use and restriction of phthalates in children's products has not been assessed. Our objective was to identify demographic, behavioral, and temporal predictors of urinary phthalate metabolite concentrations in young children. Between 2004 and 2011, we collected up to five urine samples from each of 296 children participating in a prospective birth cohort during annual study visits at ages 1-5 years. We used linear mixed models to calculate intraclass correlation coefficients (ICCs), a measure of within-individual reproducibility, and identify demographic predictors of urinary phthalate metabolites. We used multivariable linear regression to examine cross-sectional relationships between food packaging or personal care product use and phthalate metabolites measured at age 5 years. Across annual measurements, monoethyl phthalate exhibited the least variation (ICC = 0.38), while di-2-ethylhexyl phthalate (?DEHP) metabolites exhibited the most variation (ICC = 0.09). Concentrations changed with age, suggesting age-related changes in phthalate exposure and perhaps metabolism. Our findings suggest that fast food consumption may be a source of butylbenzyl phthalate and di-isononyl phthalate (DiNP) exposure, and some personal care products may be sources of diethyl phthalate exposure. Concentrations of ?DEHP metabolites decreased over the study period; however, concentrations of DiNP metabolites increased. This finding suggests that manufacturer practices and regulations, like the Consumer Product Safety Improvement Act of 2008, may decrease DEHP exposure, but additional work characterizing the nature and toxicity of replacements is critically needed.
| S-EPMC4123928 | biostudies-literature
Project description:Personal care product use is a well-established pathway of exposure for notable endocrine disrupting compounds (EDCs), including phthalates, parabens, triclosan, benzophenone-3 (BP3), and bisphenol-A. We utilized questionnaire data from the National Health and Nutrition Examination Survey 2009-2012 cycles to examine the associations between use of sunscreen and mouthwash and urinary concentrations of phthalate metabolites and phenols in a nationally representative population of US adults (n=3529). Compared with individuals who reported "Never" using mouthwash, individuals who reported daily use had significantly elevated urinary concentrations of mono-ethyl phthalate, methyl and propyl parabens, and BP3 (28%, 30%, 39%, and 42% higher, respectively). Individuals who reported "Always" using sunscreen had significantly higher urinary concentrations of triclosan, methyl, ethyl, and propyl parabens, and BP3 (59%, 92%, 102%, 151%, and 510% higher, respectively) compared with "Never" users of sunscreen. Associations between exposure biomarkers and sunscreen use were stronger in women compared with men, and associations with mouthwash use were generally stronger in men compared with women. These results suggest that sunscreen and mouthwash may be important exposure sources for EDCs.
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Project description:BackgroundPhthalates are endocrine-disrupting chemicals that are widely present in consumer products. In the United States, Black women are more highly exposed to phthalates than other racial/ethnic groups, yet information on predictors of phthalate exposure among Black women is limited.ObjectiveWe evaluated the association of demographics, lifestyle, reproductive history, and personal care product use with urinary concentrations of phthalate and phthalate alternative metabolites, using cross-sectional data from a study of 754 Black women from Detroit, Michigan (2010-2012).MethodsWomen completed questionnaires and provided urine specimens which were analyzed for 16 phthalate and phthalate alternative metabolites. We used linear regression models to estimate mean percentage differences and 95% confidence intervals (CIs) in concentrations across levels of correlates.ResultsMonoethyl phthalate (MEP) and MBP concentrations were positively associated with personal care product use, particularly nail products. Educational attainment was positively associated with high molecular weight phthalate concentrations but inversely associated with monobenzyl phthalate (MBzP) concentrations. Parity was positively associated with MBzP concentrations and inversely associated with concentrations of MEP and high molecular weight phthalates.SignificanceWe found that sociodemographics, reproductive characteristics, and use of certain personal care products were associated with urinary phthalate concentrations among Black women. Our results emphasize the importance of examining exposure determinants among multiply marginalized populations.
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