Ryan C. Lewis

Predictors of urinary bisphenol A and phthalate metabolite concentrations in Mexican children.

Exposure to endocrine disrupting chemicals such as bisphenol A (BPA) and phthalates is prevalent among children and adolescents, but little is known regarding important sources of exposure at these sensitive life stages. In this study, we measured urinary concentrations of BPA and nine phthalate metabolites in 108 Mexican children aged 8-13 years. Associations of age, time of day, and questionnaire items on external environment, water use, and food container use with specific gravity-corrected urinary concentrations were assessed, as were questionnaire items concerning the use of 17 personal care products in the past 48-h. As a secondary aim, third trimester urinary concentrations were measured in 99 mothers of these children, and the relationship between specific gravity-corrected urinary concentrations at these two time points was explored. After adjusting for potential confounding by other personal care product use in the past 48-h, there were statistically significant (p<0.05) positive associations in boys for cologne/perfume use and monoethyl phthalate (MEP), mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and in girls for colored cosmetics use and mono-n-butyl phthalate (MBP), mono(2-ethylhexyl) phthalate (MEHP), MEHHP, MEOHP, and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), conditioner use and MEP, deodorant use and MEP, and other hair products use and MBP. There was a statistically significant positive trend for the number of personal care products used in the past 48-h and log-MEP in girls. However, there were no statistically significant associations between the analytes and the other questionnaire items and there were no strong correlations between the analytes measured during the third trimester and at 8-13 years of age. We demonstrated that personal care product use is associated with exposure to multiple phthalates in children. Due to rapid development, children may be susceptible to impacts from exposure to endocrine disrupting chemicals; thus, reduced or delayed use of certain personal care products among children may be warranted.

Biomarkers of exposure to molybdenum and other metals in relation to testosterone among men from the United States National Health and Nutrition Examination Survey 2011-2012.

OBJECTIVE To examine the potential associations between biomarkers of metal exposure and serum testosterone in men of reproductive age in the general US population. DESIGN Cross-sectional epidemiology study with adjustment for potential confounders. SETTING Not applicable. PATIENT(S) Men recruited in the United States National Health and Nutrition Examination Survey (NHANES). INTERVENTION(S) Metal concentrations measured in whole blood, urine, and/or serum samples collected from 484 men. MAIN OUTCOME MEASURE(S) Serum T concentration. RESULT(S) Concentrations of the metals were detected in 69%-100% of the samples. In adjusted analyses where metals were modeled as a continuous variable, we found significant inverse associations between urinary molybdenum and serum copper and serum T, whereas there were significant positive associations between blood lead and cadmium and serum T. When metals were categorized into quartiles, analyses for serum copper and blood lead and cadmium produced significant associations in the same direction as the continuous measures. A suggestive inverse association was observed between quartiles of urinary molybdenum and serum T, but the association was statistically significant when molybdenum was categorized into quintiles. Significant positive associations were also observed for quartiles of blood Se and serum Zn and serum T. CONCLUSION(S) These findings add to the limited human evidence that exposure to molybdenum and other metals is associated with altered T in men, which may have important implications for male health. More research is needed to confirm the findings of our study.

Urinary biomarkers of exposure to insecticides, herbicides, and one insect repellent among pregnant women in Puerto Rico

BackgroundThere are potential adverse health risks to the mother and fetus from exposure to pesticides. Thus, studies of exposure to pesticides among pregnant women are of interest as they will assist with understanding the potential burden of exposure globally, identifying sources of exposure, and designing epidemiology studies.MethodsWe measured urinary concentrations of the insect repellent N-N-diethyl-meta-toluamide (DEET) and two of its metabolites [3-diethyl-carbamoyl benzoic acid (DCBA) and N,N-diethyl-3-hydroxymethylbenzamide (DHMB)], four pyrethroid insecticide metabolites [4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA); 3-phenoxybenzoic acid (3-PBA); trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (trans-DCCA); and cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DBCA)], and two chlorophenoxy herbicides [2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)] in 54 pregnant women from Puerto Rico at three separate time points (20 ± 2 weeks, 24 ± 2 weeks, and 28 ± 2 weeks of gestation). We calculated the distributions of the biomarker concentrations and compared them to those of women of reproductive age from the general U.S. population where available, and estimated the within-subject temporal variability of these repeated measurements. We also collected questionnaire data on demographics, consumption of select fruits, vegetables, and legumes in the past 48-hr, and pest-related issues, and associations between these variables and biomarker concentrations were examined.ResultsWe found that 95th percentile urinary concentrations of DEET, 3-PBA, trans-DCCA, and 2,4-D were lower than women of reproductive age on the U.S. mainland, whereas 95th percentile urinary concentrations of 4-F-3-PBA, cis-DBCA, and 2,4,5-T were similar. DCBA, the only urinary biomarker detected in >50% of the samples, showed fair to good reproducibility across pregnancy (intraclass correlation coefficient: 0.60). Women were more likely (p <0.05) to have greater urinary concentrations of pesticide biomarkers if they were less educated (DCBA and trans-DCCA), unemployed (DHMB), or married (2,4-D), had consumed collards or spinach in past 48-hr (2,4-D) or had been using insect repellent since becoming pregnant (DCBA), or were involved with residential applications of pesticides (trans-DCCA).ConclusionsWe identified concentrations and predictors of several pesticides among pregnant women in Puerto Rico. Further research is needed to understand what aspects of the predictors identified lead to greater exposure, and whether exposure during pregnancy is associated with adverse health.

Serum Biomarkers of Exposure to Perfluoroalkyl Substances in Relation to Serum Testosterone and Measures of Thyroid Function among Adults and Adolescents from NHANES 2011-2012

Perfluoroalkyl substances (PFASs) are a group of environmentally-persistent chemicals that have been widely used in many industrial applications. There is human and animal evidence that PFASs may alter levels of reproductive and thyroid-related hormones. However, human studies on the potential age-related effects of PFASs on these outcomes among males and females are limited. We explored the relationship between serum PFASs and serum total testosterone (T), thyroid stimulating hormone (TSH), and free and total triiodothyronine (FT3, TT3) and thyroxine (FT4, TT4) among males and females 12 to 80 years of age from the 2011–2012 cycle of the National Health and Nutrition Examination Survey. Associations were assessed using multiple linear regression models that were stratified on sex and age categories. Effect estimates from the majority of the adjusted models were not statistically significant. However, exposure to PFASs may be associated with increases in FT3, TT3, and FT4 among adult females, but during adolescence, PFASs may be related to increases in TSH among males and decreases in TSH among females. No significant relationships were observed between PFASs and T in any of the models. These findings suggest that exposure to PFASs may disrupt thyroid hormone homeostasis.

Personal care product use among adults in NHANES: associations between urinary phthalate metabolites and phenols and use of mouthwash and sunscreen

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.

Distribution and determinants of urinary biomarkers of exposure to organophosphate insecticides in Puerto Rican pregnant women

Globally, human exposures to organophosphate (OP) insecticides may pose a significant burden to the health of mothers and their developing fetuses. Unfortunately, relevant data is limited in certain areas of the world concerning sources of exposure to OP insecticides in pregnant populations. To begin to address this gap in information for Puerto Rico, we studied repeated measures of urinary concentrations of 10 OP insecticide metabolites among 54 pregnant women from the northern karst region of the island. We also collected demographic data and self-reported information on the consumption of fruits, vegetables, and legumes in the past 48 h before urine collection and home pest-related issues. We calculated the distributions of the urinary biomarkers and compared them to women of reproductive age from the general U.S. population. We also used statistical models accounting for correlated data to assess within-subject temporal variability of the urinary biomarkers and to identify predictors of exposure. We found that for all but two metabolites (para-nitrophenol [PNP], diethylthiophosphate [DETP]), 50th or 95th percentile urinary concentrations (the metric that was used for comparison was based on the biomarkers detection frequency) of the other eight metabolites (3,5,6-trichloro-2-pyridinol [TCPY], 2-isopropyl-4-methyl-6-hydroxy-pyrimidine, malathion dicarboxylic acid, diethylphosphate, diethyldithiophosphate, dimethylphosphate, dimethylthiophosphate [DMTP], dimethyldithiophosphate) were somewhat lower in our cohort compared with similarly aged women from the continental United States. TCPY, PNP, DETP, and DMTP, which were the only urinary metabolites detected in greater than 50% of the samples, had poor reproducibility (intraclass correlation coefficient range: 0.19-0.28) during pregnancy. Positive predictors of OP insecticide exposure included: age; marital or employment status; consumption of cherries, grape juice, peanuts, peanut butter, or raisins; and residential application of pesticides. Further research is needed to understand what aspects of the predictors identified influence OP insecticide exposure during pregnancy.

Association between urinary biomarkers of exposure to organophosphate insecticides and serum reproductive hormones in men from NHANES 1999–2002

Exposure to organophosphate (OP) insecticides may alter reproductive hormone levels in men and increase the risk for poor reductive health and other adverse health outcomes. However, relevant epidemiology studies in men are limited. We evaluated urinary concentrations of OP metabolites (3,5,6-trichloro-2-pyridinol and six dialkyl phosphates) in relation to serum concentrations of testosterone (T) and estradiol among 356 men aged 20-55 years old from the U.S. National Health and Nutrition Examination Survey. Biomarkers were detected in greater than 50% of the samples, except for diethyldithiophosphate, dimethylphosphate, and dimethyldithiophosphate. In adjusted regression models, we observed a statistically significant inverse relationship between diethyl phosphate (DEP) and T when DEP was modeled as either a continuous or categorical variable. These findings add to the limited evidence that exposure to certain OP insecticides is linked to altered T in men, which may have important implications for male health.

Exposure to Power-Frequency Magnetic Fields and the Risk of Infertility and Adverse Pregnancy Outcomes: Update on the Human Evidence and Recommendations for Future Study Designs

ABSTRACT Infertility and adverse pregnancy outcomes are significant public health concerns with global prevalence. Over the past 35 years, research has addressed whether exposure to power-frequency magnetic fields is one of the etiologic factors attributed to these conditions. However, no apparent authoritative reviews on this topic have been published in the peer-reviewed literature for nearly 15 years. This review provides an overview and critical analysis of human studies that were published in the peer-reviewed literature between 2002 and July 2015. Using PubMed, 13 epidemiology studies published during this time frame that concern exposure to magnetic fields and adverse prenatal (e.g., miscarriage), neonatal (e.g., preterm birth or birth defects), and male fertility (e.g., poor semen quality) outcomes were identified. Some of these studies reported associations whereas others did not, and study design limitations may explain these inconsistencies. Future investigations need to be designed with these limitations in mind to address existing research gaps. In particular, the following issues are discussed: (1) importance of selecting the appropriate study population, (2) need for addressing confounding due to unmeasured physical activity, (3) importance of minimizing information bias from exposure measurement error, (4) consideration of alternative magnetic field exposure metrics, and (5) implications and applications of personal exposure data that are correlated within female–male couples. Further epidemiologic research is needed, given the near ubiquitous exposures to power-frequency magnetic fields in the general population.

Temporal variability of daily personal magnetic field exposure metrics in pregnant women

Recent epidemiology studies of power-frequency magnetic fields and reproductive health have characterized exposures using data collected from personal exposure monitors over a single day, possibly resulting in exposure misclassification due to temporal variability in daily personal magnetic field exposure metrics, but relevant data in adults are limited. We assessed the temporal variability of daily central tendency (time-weighted average, median) and peak (upper percentiles, maximum) personal magnetic field exposure metrics over 7 consecutive days in 100 pregnant women. When exposure was modeled as a continuous variable, central tendency metrics had substantial reliability, whereas peak metrics had fair (maximum) to moderate (upper percentiles) reliability. The predictive ability of a single-day metric to accurately classify participants into exposure categories based on a weeklong metric depended on the selected exposure threshold, with sensitivity decreasing with increasing exposure threshold. Consistent with the continuous measures analysis, sensitivity was higher for central tendency metrics than for peak metrics. If there is interest in peak metrics, more than 1 day of measurement is needed over the window of disease susceptibility to minimize measurement error, but 1 day may be sufficient for central tendency metrics.

Personal power-frequency magnetic field exposure in women recruited at an infertility clinic: association with physical activity and temporal variability

Current epidemiologic approaches for studying exposure to power-frequency magnetic fields and the risk of miscarriage are potentially biased due to lack of attention to the relationship of exposure with physical activity and within-individual variability in exposures over time. This analysis examines these two issues using data from a longitudinal pilot study of 40 women recruited from an infertility clinic that contributed data for up to three 24-h periods separated by a median of 3.6 weeks. Physical activity was positively associated with peak exposure metrics. Higher physical activity within environments did not necessarily lead to higher peak exposures, suggesting that movement between and not within environments increases ones probability of encountering a high field source. Peak compared with central tendency metrics were more variable over time. Future epidemiology studies associated with peak exposure metrics should adjust for physical activity and collect more than 1 d of exposure measurement to reduce bias.