Exposure to glyphosate in the United States: Data from the 2013-2014 National Health and Nutrition Examination Survey.

BACKGROUND: Exposure to glyphosate, the most used herbicide in the United States, is not well characterized. We assessed glyphosate exposure in a representative sample of the U.S. population ≥ 6 years from the 2013-2014 National Health and Nutrition Examination Survey. METHODS: We quantified glyphosate in urine (N = 2,310) by ion chromatography isotope-dilution tandem mass spectrometry. We conducted univariate analysis using log-transformed creatinine-corrected glyphosate concentrations with demographic and lifestyle covariates we hypothesized could affect glyphosate exposure based on published data including race/ethnicity, sex, age group, family income to poverty ratio, fasting time, sample collection season, consumption of food categories (including cereal consumption) and having used weed killer products. We used multiple logistic regression to examine the likelihood of glyphosate concentrations being above the 95th percentile and age-stratified multiple linear regression to evaluate associations between glyphosate concentrations and statistically significant covariates from the univariate analysis: race/ethnicity, sex, age group, fasting time, cereal consumption, soft drink consumption, sample collection season, and urinary creatinine. RESULTS: Glyphosate weighted detection frequency was 81.2 % (median (interquartile range): 0.392 (0.263-0.656) µg/L; 0.450 (0.266-0.753) µg/g creatinine). Glyphosate concentration decreased from age 6-11 until age 20-59 and increased at 60+ years in univariate analyses. Children/adolescents and adults who fasted > 8 h had significantly lower model-adjusted geometric means (0.43 (0.37-0.51) µg/L and 0.37 (0.33-0.39) µg/L) than those fasting ≤ 8 h (0.51 (0.46-0.56) µg/L and 0.44 (0.41-0.48) µg/L), respectively. The likelihood (odds ratio (95 % CI)) of glyphosate concentrations being > 95th percentile was 1.94 (1.06-3.54) times higher in people who fasted ≤ 8 h than people fasting > 8 h (P = 0.0318). CONCLUSIONS: These first nationally representative data suggest that over four-fifths of the U.S. general population ≥ 6 years experienced recent exposure to glyphosate. Variation in glyphosate concentration by food consumption habits may reflect diet or lifestyle differences.

Serum elimination half-lives adjusted for ongoing exposure of tri-to hexabrominated diphenyl ethers: Determined in persons moving from North America to Australia.

The objective of the study was to determine the human serum elimination half-life of polybrominated diphenyl ethers (PBDEs) adjusted for ongoing exposure in subjects moving from a higher exposure region (North America) to a lower exposure region (Australia). The study population was comprised of exchange students and long-term visitors from North America moving to Brisbane, Australia (N = 27) and local residents (N = 23) who were followed by repeated serum sampling every other month. The local residents were sampled to adjust for ongoing exposure in Australia. Only one visitor remained in Australia for a period of time similar to the elimination half-life and had a sufficiently high initial concentration of PBDEs to derive a half-life. This visitor arrived in Australia in March of 2011 and remained in the country for 1.5 years. Since the magnitude of PBDE exposure is lower in Australia than in North America we observed an apparent 1st order elimination curve over time from which we have estimated the serum elimination half-lives for BDE28, BDE47, BDE99, BDE100, and BDE153 to be 0.942, 1.19, 1.03, 2.16, and 4.12 years, respectively. Uncertainty in the estimates were estimated using a Monte Carlo simulation. The human serum elimination half-life adjusted for ongoing exposure can allow us to assess the effectiveness and reduction in exposure in the general population following phase out of commercial penta- and octaBDE in 2004 in the United States.

Urinary Concentrations of Diisoheptyl Phthalate Biomarkers in Convenience Samples of U.S. Adults in 2000 and 2018-2019.

We know little about the potential health risks from exposure to diisoheptyl phthalate (DiHpP), a plasticizer used in commercial applications. The production of DiHpP ended in the United States in 2010, but DiHpP may still be present in phthalate diester mixtures. To investigate human exposure to DiHpP, we used three oxidative metabolites of DiHpP: Monohydroxyheptyl phthalate (MHHpP), mono-oxoheptylphthalate (MOHpP), and monocarboxyhexyl phthalate (MCHxP) as exposure biomarkers. We analyzed urine collected anonymously in 2000 (N = 144) and 2018-2019 (N = 205) from convenience groups of U.S. adults using high-performance liquid chromatography coupled with isotope-dilution high-resolution mass spectrometry. We detected MCHxP in all the samples tested in 2000 (GM = 2.01 ng/mL) and 2018-2019 (GM = 1.31 ng/mL). MHHpP was also detected in 100% of the 2018-2019 samples (GM = 0.59 ng/mL) and 96% of the 2000 urine samples analyzed (GM = 0.38 ng/mL). MOHpP was detected in 57% (2018-2019, GM = 0.03 ng/mL) and 92% (2000, GM = 0.19 ng/mL) of samples. The presence of MHHpP, MOHpP, and MCHxP in the 2018-2019 samples suggests recent exposure to DiHpP. Intercorrelations between metabolite concentrations were more significant in samples collected in 2000 than in samples collected in 2018-2019. The differences in urinary metabolite profiles and intercorrelations from samples collected during 2000 and 2018-2019 likely reflects changes in the composition of commercial DiHpP formulations before and after 2010.

Legacy and alternative per- and polyfluoroalkyl substances in the U.S. general population: Paired serum-urine data from the 2013-2014 National Health and Nutrition Examination Survey.

Concerns are heightened from detecting environmentally persistent man-made per- and polyfluoroalkyl substances (PFAS) in drinking water systems around the world. Many PFAS, including perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), remain in the human body for years. Since 1999-2000, assessment of exposure to PFOS, PFOA, and other select PFAS in the U.S. general population has relied on measuring PFAS serum concentrations in participants of the National Health and Nutrition Examination Survey (NHANES). Manufacturers have replaced select chemistries ("legacy" PFAS) with PFAS with shorter biological half-lives (e.g., GenX, perfluorobutanoate [PFBA]) which may efficiently eliminate in urine. However, knowledge regarding exposure to these compounds is limited. We analyzed 2682 urine samples for 17 legacy and alternative PFAS in 2013-2014 NHANES participants ≥6 years of age. Concentrations of some of these PFAS, measured previously in paired serum samples from the same NHANES participants, suggested universal exposure to PFOS and PFOA, and infrequent or no exposure to two short-chain PFAS, perfluorobutane sulfonate and perfluoroheptanoate. Yet, in urine, PFAS were seldom detected; the frequency of not having detectable concentrations of any of the 17 PFAS was 67.5%. Only two were detected in >1.5% of the population: PFBA (13.3%) and perfluorohexanoate (PFHxA, 22.6%); the 90th percentile urine concentrations were 0.1 µg/L (PFBA), and 0.3 µg/L (PFHxA). These results suggest that exposures to short-chain PFAS are infrequent or at levels below those that would result in detectable concentrations in urine. As such, these findings do not support biomonitoring of short-chain PFAS or fluorinated alternatives in the general population using urine, and highlight the importance of selecting the adequate biomonitoring matrix.

Exposure to neonicotinoid insecticides in the U.S. general population: Data from the 2015-2016 national health and nutrition examination survey.

BACKGROUND: Neonicotinoids are used for insect control in agriculture, landscaping, and on household pets. Neonicotinoids have become popular replacements for organophosphate and carbamate insecticides, and use is on the rise. OBJECTIVES: To assess human exposure to neonicotinoid insecticides in a representative sample of the U.S. general population 3 years and older from the 2015-2016 National Health and Nutrition Examination Survey (NHANES). METHODS: We used online solid-phase extraction coupled to isotope dilution high-performance liquid chromatography-tandem mass spectrometry after enzymatic hydrolysis of conjugates to quantify in 3038 samples the urinary concentrations of six neonicotinoid biomarkers: four parent compounds (acetamiprid, clothianidin, imidacloprid, thiacloprid) and two metabolites (N-desmethyl-acetamiprid, 5-hydroxy-imidacloprid). We calculated distribution percentiles, and used regression models to evaluate associations of various demographic parameters and fasting time with urinary concentrations above the 95th percentile (a value selected to represent higher than average concentrations) of neonicotinoid biomarkers. RESULTS: Weighted detection frequencies were 35% (N-desmethyl-acetamiprid), 19.7% (5-hydroxy imidacloprid), 7.7% (clothianidin), 4.3% (imidacloprid), and <0.5% (acetamiprid, thiacloprid). The weighted frequency of having detectable concentrations of at least one of the six biomarkers examined was 49.1%. The 95th percentile concentrations for N-desmethyl-acetamiprid, 5-hydroxy imidacloprid, and clothianidin were 1.29, 1.37, and 0.396 µg/L, respectively. For people who fasted <8 h, regardless of race/ethnicity and sex, 3-5 year old children were more likely to have N-desmethyl-acetamiprid concentrations above the 95th percentile than adolescents (adjusted odds ratio (OR) = 3.12; 95% confidence interval [CI], (0.98-9.98)) and adults (adjusted OR = 4.29; 95% CI, (2.04-9.0)); and children 6-11 years of age were more likely than adults to have N-desmethyl-acetamiprid concentrations above the 95th percentile (adjusted OR = 2.65; 95% CI, (1.2-5.84)). Asians were more likely than non-Asians to have concentrations above the 95th percentile of N-desmethyl-acetamiprid (adjusted OR = 1.94; 95% CI, (1.08-3.49)) and 5-hydroxy-imidacloprid (adjusted OR = 2.25; 95% CI, (1.44-3.51)). Samples collected during the summer were more likely to have metabolite concentrations above the 95th percentile than those collected in the winter (adjusted OR 1.55 for N-desmethyl-acetamiprid, and 2.43 for 5-hydroxy-imidacloprid). CONCLUSIONS: The detection of neonicotinoid metabolites more frequently and at much higher concentrations than the corresponding parent compounds suggests that the metabolites may be suitable biomarkers to assess background exposures. About half of the U.S. general population 3 years of age and older was recently exposed to neonicotinoids. Compared to other age ranges and ethnicities, young children and Asians may experience higher exposures. At present, reasons for such differences remain unknown.

Polybrominated Diphenyl Ethers and Biphenyl in Serum: Time Trend Study from the National Health and Nutrition Examination Survey for Years 2005/06 through 2013/14.

Eleven polybrominated diphenyl ether (tri- to deca-BDE) congeners and 2,2',4,4',5,5'-hexabromobiphenyl (BB153) have been measured in pooled serum samples from the National Health and Nutrition Examination Survey (NHANES) for one decade (from survey years 2005/06 through 2013/14). The pools, which are representative of the general noninstitutionalized population of the United States, encompassed thirty-two demographic groups defined by sex, race/ethnicity (Mexican American, non-Hispanic black, non-Hispanic white, and all other race/ethnicities), and age (12-19, >20-39, >40-59, and ≥60 years). The adjusted geometric means were determined in a multiple linear regression model for the six congeners (BDE28, BDE47, BDE99, BDE100, BDE153, and BB153) with detectable concentrations in at least 60% of pools in each of the thirty-two demographic groups; the level of significance for all statistical comparisons thereof were determined. BDE154 and BDE209 were detected in 60% of the NHANES 2011/12 and 2013/14 pools; only these two survey periods were evaluated for these congeners. The percent change in concentration by a 2-year survey period was calculated. All examined PBDEs reported in five survey periods decreased in concentration, except BDE153, for which concentrations increased by 12.0% (95% CI 7.1-16.4) and 8.4% (95% CI 2.9-14.1) for the age groups 40-59 and ≥60 years, respectively; no significant change was observed in younger age groups. Excluding BDE153, we observed larger percentage decreases by a 2-year survey period for the age groups 12-19, 20-39, and ≥60 years compared with the age group 40-59 years. The percentage decrease by a two-year survey period ranged between -19.6% (BDE99, 20-39 years old) and -4.5% (BDE100, 40-59 years old). Although five polybrominated diphenyl ether (PDBE) congeners and BB153 are still frequently detected in the U.S. general population, PBDE concentrations have decreased since 2005-2006, likely, because of changes in manufacturing practices that started in the mid-2000s.

Urinary concentrations of monohydroxylated polycyclic aromatic hydrocarbons in adults from the U.S. Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013-2014).

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants formed from incomplete combustion of organic matter; some PAHs are carcinogens. Smoking, diet, and other activities contribute to exposure to PAHs. Exposure data to PAHs among combustible tobacco product users (e.g. cigarette smokers) exist; however, among non-combustible tobacco products users (e.g., e-cigarette users), such data are rather limited. OBJECTIVES: We sought to evaluate exposure to PAHs among participants in Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health (PATH) Study based on the type of tobacco product (combustible vs non-combustible), and frequency and intensity of product use. METHODS: We quantified seven PAH urinary biomarkers in 11,519 PATH Study participants. From self-reported information, we categorized 8327 participants based on their use of tobacco products as never-tobacco user (never user, n = 1700), exclusive current established combustible products user (combustible products user, n = 5767), and exclusive current established non-combustible products user (non-combustible products user, n = 860). We further classified tobacco users as exclusive cigarette user (cigarette user, n = 3964), exclusive smokeless product user (SLT user, n = 509), and exclusive e-cigarette user (e-cigarette user, n = 280). Last, we categorized frequency of product use (everyday vs some days) and time since use (last hour, within 3 days, over 3 days). We calculated geometric mean (GM) concentrations, and evaluated associations between tobacco product user categories and PAH biomarkers concentrations. RESULTS: Combustible products users had significantly higher GMs of all biomarkers than non-combustible products users and never users; non-combustible products users had significantly higher GMs than never users for four of seven biomarkers. For all biomarkers examined, cigarette users had the highest GMs compared to other tobacco-product users. Interestingly, GMs of 2-hydroxyfluorene, 3-hydroxyfluorene and ∑2,3-hydroxyphenanthrene were significantly higher in SLT users than in e-cigarette users; 3-hydroxyfluorene and 1-hydroxypyrene were also significantly higher in e-cigarette and SLT users than in never users. Everyday cigarette and SLT users had significantly higher GMs for most biomarkers than some days' users; cigarette and SLT users who used the product in the last hour had significantly higher GMs of most biomarkers than other occasional cigarette or SLT users respectively. By contrast, everyday e-cigarette users' GMs of most biomarkers did not differ significantly from those in some days' e-cigarette users; we did not observe clear trends by time of last use among e-cigarette users. CONCLUSIONS: Users of tobacco products had higher PAH urinary biomarker concentrations compared to never users, and concentrations differed by type and frequency of tobacco product use.

Exposure to di-2-ethylhexyl terephthalate in the U.S. general population from the 2015-2016 National Health and Nutrition Examination Survey.

BACKGROUND: Di-2-ethylhexyl terephthalate (DEHTP) is used as a replacement plasticizer for other phthalates, including di-2-ethylhexyl phthalate (DEHP). Use of consumer products containing DEHTP may result in human exposure to DEHTP. OBJECTIVE: To assess exposure to DEHTP in a nationally representative sample of the U.S. general population 3 years and older from the 2015-2016 National Health and Nutrition Examination Survey (NHANES). METHOD: We quantified two DEHTP metabolites, mono-2-ethyl-5-hydroxyhexyl terephthalate (MEHHTP) and mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) in 2970 urine samples by using online solid-phase extraction coupled with isotope dilution-high-performance liquid chromatography-tandem mass spectrometry. We used linear regression to examine associations between MEHHTP and MECTPP and several parameters including age, sex, race/ethnicity, and household income. We also compared the MEHHTP and MECPTP results to those of their corresponding DEHP metabolite analogs, namely mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) and mono-2-ethyl-5-carboxypentyl phthalate (MECPP). RESULTS: The weighted detection frequencies were 96% (MEHHTP) and 99.9% (MECPTP); urinary concentrations of the two metabolites correlated significantly (Pearson correlation coefficient = 0.89, p < 0.0001). MECPTP concentrations were higher than MEHHTP in all age, sex, race/ethnicity groups examined. Furthermore, MECPTP adjusted geometric mean (GM) concentrations were significantly higher in samples collected in the evening than in the morning or afternoon. Females had significantly higher adjusted GM concentrations of MEHHTP and MECPTP than males. We observed no significant associations between the adjusted GM concentrations of the metabolites and race/ethnicity. Both metabolite adjusted GM concentrations increased significantly with household income, and decreased significantly with age. Only household income was significantly associated with the concentrations of MECPP, but not of MEHHP, the two DEHP metabolites. The adjusted GM of the [MEHHTP]:[MECPTP] molar concentrations ratio increased with age, and was significantly higher in samples collected in the morning than in those collected in the afternoon or evening. CONCLUSIONS: Exposure to DEHTP is widespread in the U.S. general population 3 years and older. These data represent the first U.S. population-based representative background exposure to DEHTP.

Polybrominated Diphenyl Ethers, Polychlorinated Biphenyls, and 2,2-Bis(4-chlorophenyl)-1,1-dichloroethene in 7- and 9-Year-Old Children and Their Mothers in the Center for the Health Assessment of Mothers and Children of Salinas Cohort.

We report longitudinal serum concentrations of select persistent organic pollutants (POPs) in children at ages 7 and 9 years and in their mothers prenatally and again when the children were 9 years old. The participating families were enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal birth cohort study of low-income Hispanic families residing in the Salinas Valley, California. We observed decreasing concentrations in the mothers with year of serum collection (2009 vs 2011) for six out of seven polybrominated diphenyl ether (PBDE) congeners and for 2,2',4,4',5-pentachlorobiphenyl (CB-99; p < 0.05). The 9-year-old children had similarly decreasing serum concentrations of all seven PBDE congeners, CB-99, and 2,2',3,4,4',5'- and 2,3,3',4,4',6-hexachlorobiphenyl (CB-138/158) with year of serum collection (2009 vs 2011; p < 0.05). In mixed effect models accounting for weight gain as the children aged from 7 to 9 years, we observed an annual decrease (-8.3% to -13.4%) in tri- to hexaBDE concentrations (p < 0.001), except for 2,2',3,4,4'-tetrabromodiphenyl ether (BDE-85) and 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153). The concentrations of these congeners were not associated with time of serum collection and instead showed an -0.9% to -2.6% decrease per kilogram of weight gain during the study period (p < 0.05). In the case of tetra- to heptachlorobiphenyls, we observed -0.5% to -0.7% decrease in serum concentration per kilogram of weight gain (p < 0.05) and -3.0% to -3.7% decrease in serum concentration per year of aging (p < 0.05), except for 2,3',4,4',5-pentachlorobiphenyl (CB-118) and 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), which were not associated with time of serum draw. 2,2-Bis(4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE) decreased -2.4%/kg of weight gain between the two sampling points (p < 0.001). These findings suggest that as children grow, dilution in a larger body size plays an important role in explaining reductions in body burden in the case of traditional POPs such as PCBs and p,p'-DDE. By contrast, in the case of PBDEs, reductions are likely explained by reduction in exposure, as illustrated by decreased concentrations in more recent years, possibly amplified by presumed shorter biological half-life than other POPs.

Exposure to organophosphate flame retardant chemicals in the U.S. general population: Data from the 2013-2014 National Health and Nutrition Examination Survey.

BACKGROUND: Use of organophosphate flame retardants (OPFRs) including tris(1,3-dichloro-2-propyl) phosphate, triphenyl phosphate, tris(1-chloro-2-propyl) phosphate, and tris-2-chloroethyl phosphate, in consumer products is on the rise because of the recent phase out of polybrominated diphenyl ether (PBDE) flame retardants. Some of these chemicals are also used as plasticizers or lubricants in many consumer products. OBJECTIVES: To assess human exposure to these chlorinated and non-chlorinated organophosphates, and non-PBDE brominated chemicals in a representative sample of the U.S. general population 6years and older from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). METHODS: We used solid-phase extraction coupled to isotope dilution high-performance liquid chromatography-tandem mass spectrometry after enzymatic hydrolysis of conjugates to analyze 2666 NHANES urine samples for nine biomarkers: diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis-(1-chloro-2-propyl) phosphate (BCIPP), bis-2-chloroethyl phosphate (BCEP), di-n-butyl phosphate (DNBP), di-p-cresylphosphate (DpCP), di-o-cresylphosphate (DoCP), dibenzyl phosphate (DBzP), and 2,3,4,5-tetrabromobenzoic acid (TBBA). We calculated the geometric mean (GM) and distribution percentiles for the urinary concentrations (both in micrograms per liter [µg/L] and in micrograms per gram of creatinine). We only calculated GMs for analytes with an overall weighted frequency of detection >60%. For those analytes, we also a) determined weighted Pearson correlations among the log10-transformed concentrations, and b) used regression models to evaluate associations of various demographic parameters with urinary concentrations of these biomarkers. RESULTS: We detected BDCIPP and DPHP in approximately 92% of study participants, BCEP in 89%, DNBP in 81%, and BCIPP in 61%. By contrast, we detected the other biomarkers much less frequently: DpCP (13%), DoCP (0.1%), TBBA (5%), and did not detect DBzP in any of the participants. Concentration ranges were highest for DPHP (<0.16-193µg/L), BDCIPP (<0.11-169µg/L), and BCEP (<0.08-110µg/L). Regardless of race/ethnicity, 6-11year old children had significantly higher BCEP adjusted GMs than other age groups. Females had significantly higher DPHP and BDCIPP adjusted GM than males, and were more likely than males to have DPHP concentrations above the 95th percentile (odds ratio=3.61; 95% confidence interval, 2.01-6.48). CONCLUSIONS: Our results confirm findings from previous studies suggesting human exposure to OPFRs, and demonstrate, for the first time, widespread exposure to several OPFRs among a representative sample of the U.S. general population 6years of age and older. The observed differences in concentrations of certain OPFRs biomarkers by race/ethnicity, in children compared to other age groups, and in females compared to males may reflect differences in lifestyle and exposure patterns. These NHANES data can be used to stablish a nationally representative baseline of exposures to OPFRs and when combined with future 2-year survey data, to evaluate exposure trends.

Per- and polyfluoroalkyl substances in sera from children 3 to 11 years of age participating in the National Health and Nutrition Examination Survey 2013-2014.

Several per- and polyfluoroalkyl substances (PFAS) have been measured in U.S. National Health and Nutrition Examination Survey (NHANES) participants 12 years of age and older since 1999-2000, but PFAS data using NHANES individual samples among children younger than 12 years do not exist. To obtain the first nationally representative PFAS exposure data in U.S. children, we quantified serum concentrations of 14 PFAS including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), in a nationally representative subsample of 639 3-11year old participants in NHANES 2013-2014. We used on-line solid-phase extraction coupled to isotope dilution-high performance liquid chromatography-tandem mass spectrometry; limits of detection were 0.1ng/mL for all analytes. We calculated geometric mean concentrations, determined weighted Pearson correlations, and used linear regression to evaluate associations of sex, age (3-5 vs 6-11 years), race/ethnicity (Hispanic vs non-Hispanic), household income, and body mass index with concentrations of PFAS detected in more than 60% of participants. We detected PFOS, PFOA, PFHxS, and PFNA in all children at concentrations similar to those of NHANES 2013-2014 adolescents and adults, suggesting prevalent exposure to these PFAS or their precursors among U.S. 3-11year old children, most of whom were born after the phase out of PFOS in the United States in 2002. PFAS concentration differences by sex, race/ethnicity, and age suggest lifestyle differences that may impact exposure, and highlight the importance of identifying exposure sources and of studying the environmental fate and transport of PFAS.

Exposure to di-2-ethylhexyl terephthalate in a convenience sample of U.S. adults from 2000 to 2016.

Di-2-ethylhexyl terephthalate (DEHTP), a structural isomer of di-2-ethylhexyl phthalate (DEHP), is a plasticizer used in a variety of commercial applications, but data on Americans' exposure to DEHTP do not exist. We investigated the exposure to DEHTP in a convenience group of U.S. adults by analyzing urine collected anonymously in 2000 (N = 44), 2009 (N = 61), 2011 (N = 81), 2013 (N = 92), and 2016 (N = 149) for two major DEHTP oxidative metabolites: mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) and mono-2-ethyl-5-hydroxyhexyl terephthalate (MEHHTP). For comparison, we also quantified the analogous DEHP metabolites mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) and mono-2-ethyl-5-carboxypentyl phthalate (MECPP). We detected MECPTP, MEHHP, and MECPP in all samples collected in 2016 with geometric means of 13.1, 4.1, and 6.7 ng/mL, respectively; we detected MEHHTP in 91% of the samples (geometric mean = 3.1 ng/mL). Concentrations of MECPTP correlated well with those of MEHHTP (R 2 = 0.8, p < 0.001), but did not significantly correlate with those of MEHHP (p > 0.05) suggesting different sources of exposure to DEHP and DEHTP. We also evaluated the fraction of the metabolites eliminated in their free (i.e., unconjugated) form. The median percent of unconjugated species was lower for the DEHP metabolites (MECPP [45.5%], MEHHP [1.9%]) compared to the DEHTP metabolites (MECPTP [98.8%], MEHHTP [21.2%]). Contrary to the downward trend from 2000 to 2016 in urinary concentrations of MEHHP and MECPP, we observed an upward trend for MEHHTP and MECPTP. These preliminary data suggest that exposure to DEHTP may be on the rise. Nevertheless, general population exposure data using MEHHTP and MECPTP as exposure biomarkers would increase our understanding of exposure to DEHTP, one of the known DEHP alternatives.

Co-exposure to non-persistent organic chemicals among American pre-school aged children: A pilot study.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Urinary Concentrations of the Antibacterial Agent Triclocarban in United States Residents: 2013-2014 National Health and Nutrition Examination Survey.

Triclocarban is widely used as an antibacterial agent in personal care products, and the potential for human exposure exists. We present here the first nationally representative assessment of exposure to triclocarban among Americans ≥6 years of age who participated in the 2013-2014 National Health and Nutrition Examination Survey. We detected triclocarban at concentrations above 0.1 µg/L in 36.9% of 2686 urine samples examined. Triclocarban was detected more frequently in adolescents and adults than in children, and in non-Hispanic black compared to other ethnic groups. In univariate analysis, log-creatinine, sex, age, race, and body surface area (BSA) were significantly associated with the likelihood of having triclocarban concentrations above the 95th percentile. In multiple regression models, persons with BSA at or above the median (≥1.86 m2) were 2.43 times more likely than others, and non-Hispanic black and non-Hispanic white were 3.71 times and 2.23 times more likely than "all Hispanic," respectively, to have urinary concentrations above the 95th percentile. We found no correlations between urinary concentrations of triclocarban and triclosan, another commonly used antibacterial agent. Observed differences among demographic groups examined may reflect differences in physiological factors (i.e., BSA) as well as use of personal care products containing triclocarban.

Thyroid antagonists and thyroid indicators in U.S. pregnant women in the Vanguard Study of the National Children's Study.

The sodium iodide-symporter (NIS) mediates uptake of iodide into thyroid follicular cells. This key step in thyroid hormone synthesis is inhibited by perchlorate, thiocyanate (SCN) and nitrate (NO3) anions. When these exposures occur during pregnancy the resulting decreases in thyroid hormones may adversely affect neurodevelopment of the human fetus. Our objectives were to describe and examine the relationship of these anions to the serum thyroid indicators, thyroid stimulating hormone (TSH) and free thyroxine (FT4), in third trimester women from the initial Vanguard Study of the National Children's Study (NCS); and to compare urine perchlorate results with those in pregnant women from the National Health and Nutritional Examination Survey (NHANES). Urinary perchlorate, SCN, NO3, and iodine, serum TSH, FT4, and cotinine were measured and a food frequency questionnaire (FFQ) was administered to pregnant women enrolled in the initial Vanguard Study. We used multiple regression models of FT4 and TSH that included perchlorate equivalent concentration (PEC, which estimates combined inhibitory effects of the anions perchlorate, SCN, and NO3 on the NIS). We used multiple regression to model predictors of each urinary anion, using FFQ results, drinking water source, season of year, smoking status, and demographic characteristics. Descriptive statistics were calculated for pregnant women in NHANES 2001-2012. The geometric mean (GM) for urinary perchlorate was 4.04µg/L, for TSH 1.46mIU/L, and the arithmetic mean for FT4 1.11ng/dL in 359 NCS women. In 330 women with completed FFQs, consumption of leafy greens, winter season, and Hispanic ethnicity were significant predictors of higher urinary perchlorate, which differed significantly by study site and primary drinking water source, and bottled water was associated with higher urinary perchlorate compared to filtered tap water. Leafy greens consumption was associated with higher urinary NO3 and higher urinary SCN. There was no association between urinary perchlorate or PEC and TSH or FT4, even for women with urinary iodine <100µg/L. GM urinary perchlorate concentrations in the full sample (n=494) of third trimester NCS women (4.03µg/L) were similar to pregnant women in NHANES (3.58µg/L).

Novel exposure biomarkers of N,N-diethyl-m-toluamide (DEET): Data from the 2007-2010 National Health and Nutrition Examination Survey.

BACKGROUND: N,N-diethyl-m-toluamide (DEET) is a widely used insect repellent in the United States. OBJECTIVES: To assess exposure to DEET in a representative sample of persons 6years and older in the U.S. general population from the 2007-2010 National Health and Nutrition Examination Survey. METHODS: We analyzed 5348 urine samples by using online solid-phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry. We used regression models to examine associations of various demographic parameters with urinary concentrations of DEET biomarkers. RESULTS: We detected DEET in ~3% of samples and at concentration ranges (>0.08µg/L-45.1µg/L) much lower than those of 3-(diethylcarbamoyl)benzoic acid (DCBA) (>0.48µg/L-30,400µg/L) and N,N-diethyl-3-hydroxymethylbenzamide (DHMB) (>0.09µg/L-332µg/L). DCBA was the most frequently detected metabolite (~84%). Regardless of survey cycle and the person's race/ethnicity or income, adjusted geometric mean concentrations of DCBA were higher in May-Sep than in Oct-Apr. Furthermore, non-Hispanic whites in the warm season were more likely than in the colder months [adjusted odds ratio (OR)=10.83; 95% confidence interval (CI), 3.28-35.79] and more likely than non-Hispanic blacks (OR=3.45; 95% CI, 1.51-7.87) to have DCBA concentrations above the 95th percentile. CONCLUSIONS: The general U.S. population, including school-age children, is exposed to DEET. However, reliance on DEET as the sole urinary biomarker would likely underestimate the prevalence of exposure. Instead, oxidative metabolites of DEET are the most adequate exposure biomarkers. Differences by season of the year based on demographic variables including race/ethnicity likely reflect different lifestyle uses of DEET-containing products.

Urinary Concentrations of Bisphenol A and Three Other Bisphenols in Convenience Samples of U.S. Adults during 2000-2014.

Because of regulatory actions and public concerns, the use of bisphenol A (BPA) may decrease, while the use of BPA alternatives may increase. Although BPA alternatives are considered safer than BPA, their effects on health are still largely unknown. For risk assessment, understanding exposure to these chemicals is necessary. We measured the urinary concentrations of BPA and three bisphenol analogs, bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF), in 616 archived samples collected from convenience samplings of U.S. adults at eight time points between 2000 and 2014. We detected BPA at the highest frequency and geometric mean (GM) concentrations (74-99%, 0.36-2.07 µg/L), followed by BPF (42-88%, 0.15-0.54 µg/L) and BPS (19-74%, < 0.1-0.25 µg/L); BPAF was rarely detected (<3% of all samples). Although concentrations of BPF were generally lower than for other bisphenols, the 95th percentile concentration of BPF was often comparable or higher than that of BPA. We did not observe obvious exposure trends for BPF. However, the significant changes in GM concentrations of BPA and BPS suggest that exposures may be declining (BPA) or on the rise (BPS). Nationally representative data will be useful to confirm these findings and to allow monitoring future exposure trends to BPA and some of its bisphenol alternatives.

Serum PCB concentrations in residents of Calcasieu and Lafayette Parishes, Louisiana with comparison to the U.S. population.

In 2002, a cross-sectional study designed to compare the serum dioxin toxic equivalent concentrations (TEQ) of a population-based sample of Calcasieu Parish, Louisiana residents, to Lafayette Parish was conducted. The mono-ortho polychlorinated biphenyls (PCBs) were measured in order to calculate the TEQ. We compared the sum of lipid adjusted serum concentrations of 27 PCB congeners (total PCBs) in residents of these two parishes and also by their demographic characteristics. The geometric means (GM) [standard errors (SE)] of the concentrations (ngg(-1) lipids) of total PCBs in participants from Calcasieu Parish and Lafayette Parish were 154 (11.8) and 168.6 (20.8) (T-test p=0.54), respectively. Various percentiles of the distribution of serum total PCB concentrations were similar in the two parishes. After adjusting by age and race in the ANCOVA regression model, the adjusted GM for the lipid adjusted total PCBs was statistically higher in the residents in Lafayette than in Calcasieu Parish regardless of age or race (P=0.007). The adjusted GM of lipid adjusted total PCBs for African Americans was significantly higher than for Whites (p<0.001). Serum total PCB levels in residents of both parishes increased linearly with age (P<0.001). The congener profiles were similar in residents of both parishes. We also compared the GMs of a sum of 8 PCBs in Calcasieu and Lafayette Parish residents to those from a representative sample of the U.S. general population in 2001-2002 and they were not significantly different between parishes or between the parish data and the U.S. general population.

Persistent organic pollutants (POPs) and metals in primiparous women: a comparison from Canada and Mexico.

Under the North American Commission for Environmental Cooperation (CEC) and its Sound Management of Chemicals (SMOC) program, a tri-national human contaminant monitoring initiative was completed to provide baseline exposure information for several environmental contaminants in Canada, Mexico and the United States (U.S). Blood samples were collected from primiparous women in Canada and Mexico, and were analysed for a suite of environmental contaminants including polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene(p,p'-DDE),beta-hexachlorocyclohexane (ß-HCH), mercury and lead. A multiple stepwise linear regression analysis was conducted using data from Canadian and Mexican primiparous mothers, adjusting for ethnicity group, age, pre-pregnancy BMI, years at current city and ever-smoking status. Concentrations of p,p'-DDE, ß-HCH, and lead were found to be higher among Mexican participants; however, concentrations of most PCBs among Mexican participants were similar to Canadian primiparous women after adjusting for covariates. Concentrations of total mercury were generally higher among Mexican primiparous women although this difference was smaller as age increased. This initial dataset can be used to determine priorities for future activities and to track progress in the management of the selected chemicals, both domestically and on a broader cooperative basis within North America.