Urinary organophosphate ester concentrations in relation to ultra-processed food consumption in the general US population.

Ultra-processed foods are highly processed foods which are manufactured with industrial substances to increase convenience and palatability. Some organophosphate esters (OPEs) are used as flame retardants and plasticizers and have been detected in food samples, particularly processed foods. However, little is known about dietary sources of OPEs or whether higher consumption of ultra-processed foods increases exposures. We evaluated whether higher consumption of ultra-processed food is associated with urinary OPE metabolite concentrations in a nationally representative sample of US children and adults. Among 2242 participants (≥6 years) in the National Health and Nutrition Examination Survey (NHANES) 2013-2014, we used the NOVA classification system to calculate percent of total energy from ultra-processed food using a 24 h dietary recall. Concentrations of 7 OPE metabolites, including diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(2-chloroethyl) phosphate (BCEP), dibutyl phosphate (DBUP), di-p-cresyl phosphate (DPCP), 2,3,4,5-tetrabromobenzoic acid (TBBA), and bis(1-chloro-2-propyl) phosphate (BCPP) were measured in urine. We used multivariable linear or logistic regressions to examine associations per 10% higher total energy from ultra-processed foods with percent changes or prevalence of detectable levels of creatinine-standardized OPEs. In a model adjusting for only urinary creatinine, each 10% higher total energy from ultra-processed food was associated with 3.5% (95% CI: 0.7%, 6.3%) higher DPHP and 8.2% (95% CI: 4.6, 11.9%) higher BDCPP concentrations. However, none of the OPE metabolites was associated with ultra-processed food consumption in models adjusted for sociodemographic characteristics, health behaviors, and BMI (all p-values >0.05). Ultra-processed breads and tortillas; sauces, dressing, and gravies; and milk-based drinks were associated with higher concentrations of BDCPP while frozen and shelf-stable plate meals were associated with lower concentrations. Reconstituted meat or fish products and ultra-processed milk-based desserts were associated with greater odds of detectable levels of BCPP. While some food groups were associated with urinary OPE metabolite concentrations, ultra-processed foods do not appear to be a major source of current OPE exposure in the US.

Kim H ，Rebholz CM ，Wong E ，Buckley JP ... -  《-》

Associations between urinary organophosphate ester metabolites and measures of adiposity among U.S. children and adults: NHANES 2013-2014.

Organophosphate esters (OPEs) are synthetic chemicals found in many consumer products, including furniture, electronics, processed foods, and building materials. Emerging in vitro and in vivo studies suggest that OPEs are metabolism disrupting compounds; however, epidemiologic studies investigating their associations with adiposity markers are sparse. We examined cross-sectional associations between OPE biomarkers and adiposity measures among U.S. children and adults participating in the National Health and Nutrition Examination Survey (NHANES: 2013-2014). Concentrations of five OPE metabolites were quantified in urine: diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(2-chloroethyl) phosphate (BCEP), dibutyl phosphate (DBUP), and bis(1-chloro-2-propyl) phosphate (BCPP). We conducted covariate-adjusted logistic and linear regressions to examine associations between log2-transformed and dichotomized OPE metabolite concentrations and obesity, body mass index (BMI), and waist circumference (WC), separately among 784 children (6-19 years) and 1672 adults (≥20 years). We also assessed heterogeneity of associations by sex. DBUP concentrations were inversely associated with the prevalence odds of being obese vs. normal weight in children (adjusted Prevalence Odds Ratio, aPOR: 0.82, 95% Confidence Interval, 95% CI: 0.70, 0.95) and adults (aPOR: 0.83, 95% CI: 0.72, 0.96). DBUP was also significantly associated with lower BMI z-scores (β:-0.08, 95% CI:-0.17, 0.01) and WC (β:-0.71, 95% CI: -1.49, 0.07) in children. BCEP concentrations were associated with increased prevalence odds of being overweight vs. normal weight (aPOR: 1.15, 95% CI: 1.01, 1.32) among children; similar, albeit not statistically significant, relationships were observed with other child adiposity outcomes. Among adults, detectable BCPP concentrations were associated with increased prevalence odds of being obese vs. normal weight (aPOR: 1.70, 95% CI: 1.21, 2.38) and having a high vs. normal WC (aPOR: 1.51, 95% CI: 1.11, 2.07) as well as higher BMI (β: 1.31, 95% CI: 0.30, 2.33). Other OPE metabolites were not consistently associated with adiposity measures among adults. Although associations of BCPP exposure with adiposity outcomes were generally inverse among boys, but not girls, we did not observe consistent evidence of sexually-dimorphic associations for other OPE metabolites. Exposure to select OPEs may be differentially associated with body size among children and adults. Given the cross-sectional design of the present study, future prospective studies are needed to confirm these findings.

Boyle M ，Buckley JP ，Quirós-Alcalá L 《-》

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

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. 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). 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. 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). 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.

Ospina M ，Jayatilaka NK ，Wong LY ，Restrepo P ，Calafat AM ... -  《-》

Urinary metabolites of organophosphate esters in children in South China: Concentrations, profiles and estimated daily intake.

Organophosphate esters (OPEs) are widely used in household products as flame retardants or plasticizers and have become ubiquitous pollutants in environmental media. However, little is known about OPE metabolites in humans, especially in children. In this study, eight OPE metabolites were measured in 411 urine samples collected from 6 to 14-year-old children in South China. Bis(2-chloroethyl) phosphate (BCEP), bis(1-chloro-2-propyl) phosphate (BCIPP) and diphenyl phosphate (DPHP) were the dominant OPE metabolites, and their median concentrations were 1.04, 0.15 and 0.28 μg/L, respectively. The levels of urinary OPE metabolites in the present study were much lower than those in participants from other countries, with the exception of BCEP, suggesting widespread exposure to tris(2-chlorethyl) phosphate (TCEP, the parent chemical of BCEP) in South China. No significant difference in the concentrations of any of the OPE metabolites was observed between males and females (p > .05). Significant negative correlations were observed between age and BCEP, BCIPP, bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), di-o-cresyl phosphate (DoCP) and di-p-cresyl phosphate (DpCP) (DCP), or DPHP (p < .05). Pearson correlation coefficients between urinary OPE metabolites indicated multiple sources and OPE exposure pathways in children. The estimated daily intake suggested that children in South China have a relatively high exposure level to TCEP. To the best of our knowledge, this is the first study to report the urinary levels of OPE metabolites in Chinese children.

Chen Y ，Fang J ，Ren L ，Fan R ，Zhang J ，Liu G ，Zhou L ，Chen D ，Yu Y ，Lu S ... -  《-》

Variability and predictors of urinary organophosphate ester concentrations among school-aged children.

Organophosphate esters (OPE) are flame retardants and plasticizers used in a wide range of consumer products. Despite their widespread use, few studies have characterized pediatric exposures. We assessed variability and predictors of OPE exposures in a cohort panel study of 179 predominantly Black school-aged children with asthma in Baltimore City, MD. The study design included up to four seasonal week-long in-home study visits with urine sample collection on days 4 and 7 of each visit (nsamples = 618). We quantified concentrations of 9 urinary OPE biomarkers: bis(2-chloroethyl) phosphate (BCEtp), bis(1-chloro-2-propyl) phosphate, bis(1,3-dichloro-2-propyl) phosphate (BDCPP), di-benzyl phosphate (DBuP), di-benzyl phosphate, di-o-cresylphosphate, di-p-cresylphosphate (DPCP), di-(2-propylheptyl) phthalate (DPHP), 2,3,4,5-tetrabromo benzoic acid. We assessed potential predictors of exposure, including demographic factors, household characteristics, and cleaning behaviors. We calculated Spearman/tetrachoric correlations and intraclass correlation coefficients (ICCs) to examine within-week and seasonal intra-individual variability, respectively. We assessed OPE predictors using linear models for continuous log2 concentrations (BDCPP and DPHP) and logistic models for odds of detection (BCEtP, DBuP, DPCP), with generalized estimating equations to account for repeated measures. For all OPEs, we observed moderate within-week correlations (rs: 0.31-0.63) and weak to moderate seasonal reliability (ICC: 0.18-0.38). BDCPP and DPHP concentrations were higher in the summer compared to other seasons. DPHP concentrations were lower among males than females (%diff: -53.5%; 95% CI: -62.7, -42.0) and among participants spending >12 h/day indoors compared to ≤12 h (%diff: -20.7%; 95% CI: -32.2, -7.3). BDCPP concentrations were lower among children aged 8-10 years compared to 5-7 years (%diff: -39.1%; 95% CI: -55.9, -15.9) and higher among children riding in a vehicle on the day of sample collection compared to those who had not (%diff: 28.5%; 95% CI: 3.4, 59.8). This study is the first to characterize within-week and seasonal variability and identify predictors of OPE biomarkers among Black school-aged children, a historically understudied population.

Louis LM ，Quirós-Alcalá L ，Kuiper JR ，Diette G ，Hansel NN ，McCormack MC ，Meeker JD ，Buckley JP ... -  《-》