Bis(2-chloroethyl) Phosphate Research Articles

Gestational exposure to organophosphate esters and infant anthropometric measures in the first 4 weeks after birth.

Few studies have examined whether gestational exposure to organophosphate esters (OPEs), widely used chemicals with potential endocrine-disrupting potency and developmental toxicity, is associated with impaired infant growth. We analyzed data from 329 mother-infant pairs in the Health Outcomes and Measures of the Environment (HOME) Study (2003-2006, Cincinnati, Ohio, USA). We quantified concentrations of four OPE metabolites in maternal urine collected at 16 and 26 weeks of gestation, and at delivery. We calculated z-scores using 2006 World Health Organization (WHO) child growth standards for the 4-week anthropometric measures (weight, length, and head circumference), the ponderal index, and weekly growth rates. We used multiple informant models to examine window-specific associations between individual OPE metabolites and anthropometric outcomes. We further modeled OPEs as a mixture for window-specific associations with 4-week anthropometric outcomes using mean field variational Bayesian inference procedure for lagged kernel machine regression (MFVB-LKMR). We stratified the models by infant sex. Diphenyl phosphate (DPHP) in mothers at 16 weeks, and bis(2-chloroethyl) phosphate (BCEP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) at delivery were positively associated with z-scores of weight, length, and head circumference in all infants at 4 weeks of age. After stratifying by infant sex, positive associations were only observed in males for DPHP at 16 weeks and BCEP at delivery and in females for BDCIPP at delivery. Negative associations not present in all infants were observed in males for di-n-butyl phosphate (DNBP) at 26 weeks of gestation with weight z-score and DPHP at delivery with head circumference z-score. Results were generally similar using MFVB-LKMR models with more conservative 95 % credible intervals. We did not identify consistent associations of gestational OPE metabolite concentrations with the ponderal index and weekly growth rates. In this cohort, exposure to OPEs during gestation was associated with altered infant anthropometry at 4 weeks after birth.

Determination of organophosphate diesters in facility vegetable soils using ultra-high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry

Organophosphate diesters (Di-OPEs) are biotic or abiotic degradation products of organophosphate esters (OPEs). Current analytical methods focus on detecting Di-OPEs in human urine. Human exposure to Di-OPEs in environmental matrices has not been systematically studied. Soil plays an important role in the environmental migration and transformation of organic pollutants. Previous studies found that OPEs are ubiquitous in soil. However, few studies reported OPEs metabolite pollution in soil, especially in facility vegetable soil. In this study, an ultra-high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry (UPHLC-Orbitrap HRMS) method was developed for the determination of five Di-OPEs (bis(2-chloroethyl) phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCP), di-n-butyl phosphate (DnBP), diphenyl phosphate (DPhP), and bis(2-ethylhexyl) phosphate (DEHP)) in the facility vegetable soil. The pretreatment process and chromatographic and mass spectrometric conditions were optimized in the present study. Comparative study of the purification effects of different solid-phase extraction columns showed that Oasis WAX cartridge had best purification efficiency for the five Di-OPEs. The cartridge was first activated using 3 mL methanol, 3 mL methanol containing 5% (v/v) ammonia, and 3 mL 0.1 mol/L sodium acetate-acetic acid buffer solution. Then, the cartridge was rinsed with 3 mL of 30% (v/v) methanol aqueous solution, and finally eluted using 8 mL methanol containing 5% (v/v) ammonia. The effects of mobile phase (with respect to solvent composition and flow rate) and column temperature on the shape and intensity of chromatographic peaks were studied. The optimized UHPLC conditions were as follows: chromatographic column, Thermo Accucore RP-MS; column temperature, 30 ℃; mobile phase, 0.2 mmol/L ammonium acetate aqueous solution and methanol; flow rate, 0.2 mL/min. In the UHPLC-Orbitrap HRMS experiment, the five Di-OPEs were analyzed in full MS mode with negative ionization. Instrumental parameters, such as sheath gas and auxiliary gas, were optimized to determine the MS conditions. The optimized Orbitrap HRMS conditions were as follows: heating electrospray ionization source (HESI), full MS mode with negative ionization; scan range, m/z 100-500; ion transfer tube temperature, 320 ℃; automatic gain control of target particle count, 1×106; sheath gas flow rate, 8.58 L/min; auxiliary gas flow rate, 17.40 L/min; spray voltage, 3.2 kV; and S-lens voltage, 50 V. The limits of detection and quantification were 0.001-0.047 ng/g and 0.004-0.156 ng/g, respectively. The correlation coefficients of the calibration curve were 0.9985-0.9999. At three spiked levels, 5.0, 25.0, and 50.0 ng/g, the recoveries of the five Di-OPEs ranged from 56.9% to 133.0% with relative standard deviations of 4.4%-18.9%. The established method was applied to the analysis of the five Di-OPEs in 16 facility vegetable soils. The detection frequencies of the five Di-OPEs exceeded 60% in all soil samples, indicating that the Di-OPEs were ubiquitous in the facility vegetable soil. The contents of the five Di-OPEs in the facility vegetable soil samples ranged from 2.53-6.94 ng/g. DnBP (1.37-3.20 ng/g) and DPhP (0.47-2.44 ng/g) were the predominant congeners in the facility vegetable soil samples, accounting for 23.4%-68.8% and 16.3%-35.9% of the five Di-OPEs, respectively. The developed method is simple, sensitive, and reproducible and can be used effectively for the determination of Di-OPEs in soil. The results of this study will be helpful for understanding the environmental behavior of Di-OPEs and their human exposure in facility vegetable soils.

Chlorinated Organophosphate Flame Retardants Impair the Lung Function via the IL-6/JAK/STAT Signaling Pathway.

Toxicological studies have revealed the adverse impacts of organophosphate flame retardants (OPFRs) on the respiratory system, while there is a lack of epidemiological evidence, and information for risk assessment remains insufficient. Herein, we investigated the associations of urinary metabolites of OPFRs with the lung function in 987 adults participating in the U.S. National Health and Nutrition Examination Survey 2011-2012. The elevation of three primary metabolites of chlorinated OPFRs [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis(2-chloroethyl) phosphate (BCEP), and bis(1-chloro-2-propyl) phosphate (BCIPP)] was related to pulmonary dysfunction in a sample-weighted regression model. Each one-unit increase in the log-transformed levels of BDCIPP and BCEP was related to 91.52 and 79.34 mL reductions in the forced vital capacity (FVC). Each one-unit elevation in BCIPP was correlated with 130.86, 153.56, 302.26, and 148.24 mL reductions in forced expiratory volume 1st second (FEV1), FVC, peak expiratory flow rate (PEF), and forced expiratory flow at 25-75% of FVC (FEF25-75%), respectively. Then, an adverse outcome pathway (AOP) framework was constructed using the Comparative Toxicogenomics Database, the Toxicity Forecaster, and the GeneCards database. Based on the weight of the evidence, BDCIPP, BCEP, BCIPP, and their parent compounds (TDCIPP, TCEP, and TCIPP) may affect the IL-6/Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, induce airway remodeling, and impair the lung function. Additionally, tobacco smoke exposure may modify the effects of BDCIPP on the lung function (Pint < 0.05) and affect the IL-6-mediated AOP. These results suggested that chlorinated OPFRs were associated with pulmonary dysfunction via the IL-6/JAK/STAT pathway.

Exploratory analysis of the association between organophosphate ester mixtures with high blood pressure of children and adolescents aged 8-17years: cross-sectional findings from the National Health and Nutrition Examination Survey.

Epidemiological studies on the effect of organophosphate esters (OPEs) on high blood pressure (BP) among children and adolescents are scant. Therefore, the main objective of the present study was to explore the effect of exposure to OPEs on high BP among children and adolescents. A total of 1340 participants were included in the current analyses. Multivariable logistic regression models were implemented to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to examine the association between OPE metabolites and high BP. We also assessed the modified effect of sex, age, and overweight/obesity on this association. Furthermore, quantile g-computation (Qgcomp) and Bayesian kernel machine regression (BKMR) were exhibited to analyze the association between multiple OPE metabolite mixtures and high BP. After adjusting for covariates, the highest (vs. lowest) tertiles of bis (1-choloro-2-propyl) phosphate (BCPP), bis-2-chloroethyl phosphate (BCEP), and di-n-butyl phosphate (DBUP) were associated with 1.23 (95% CI: 0.83, 1.83), 1.27 (95% CI: 0.85, 1.92), and 1.01 (95% CI: 0.67, 1.53) odds ratios for high BP, respectively. In the Qgcomp, a quartile increase in OPE metabolite mixtures was weakly associated with an elevated risk of high BP (adjusted OR: 1.06, 95CI%: 0.81, 1.37). The results from BKMR showed a positive trend of association between OPE metabolite mixture on the risk of high BP. In conclusion, our study demonstrated that higher levels of BCPP, BCEP, and DBUP were weakly associated with high BP among US children and adolescents. Moderate evidence suggested OPE metabolite mixtures had positive joint effects on high BP. Consequently, longitudinal studies with repeated measurements are warranted to examine the relationships between multiple OPE metabolites and high blood pressure among children and adolescents.

Associations of gestational exposure to organophosphate esters with gestational age and neonatal anthropometric measures: The HOME study

Organophosphate esters (OPEs) are developmental toxicants in experimental studies of animals, but limited evidence is available in humans. We included 340 mother-infant pairs in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, Ohio, USA) for the analysis. We evaluated gestational exposure to OPEs with gestation age at birth and newborn anthropometric measures. We quantified four OPE urinary metabolites at 16 weeks and 26 weeks of gestation. We extracted gestational age at birth, newborn weight, length, and head circumference from the chart review. We calculated z-scores for these anthropometric measures and the ponderal index. We used multiple informant models to examine the associations between repeated OPE measurements and the outcomes. We used modified Poisson regression to estimate the association of gestational exposure to OPEs with preterm birth. We also explored effect modification by infant sex and the potential mediation effect by the highest maternal blood pressure and glucose levels. We found that bis(2-chloroethyl) phosphate (BCEP) at 16 weeks and diphenyl phosphate at 26 weeks of pregnancy were positively associated with gestational age and inversely associated with preterm birth. In female newborns, BCEP at 16 weeks was inversely related to birth weight and length z-scores. In male newborns, we observed negative associations of 26-week di-n-butyl phosphate with the ponderal index at birth. No mediation by the highest maternal blood pressure or glucose levels during pregnancy was identified. In this cohort, gestational exposure to some OPEs was associated with gestational age, preterm birth, and neonatal anthropometric measures. Certain associations tended to be window- and infant sex-specific.

The associations between renal disease severity and exposure to organophosphate flame retardants in patients with chronic kidney disease

Organophosphate flame retardants (OPFRs) are emerging and widespread environmental pollutants with potential health hazards, including nephrotoxicity. However, the exposure patterns and nephrotoxic potential of OPFRs are yet to be investigated in patients with chronic kidney disease (CKD). We conducted a cross-sectional study involving 166 patients with CKD stratified by estimated glomerular filtration rate (eGFR) and severity of proteinuria. The urinary concentrations of 10 OPFR compounds were measured to evaluate the exposure patterns. Clinical and urinary OPFR profiles were compared among subgroups to identify whether the OPFR compounds were independently correlated with eGFR and proteinuria. Additionally, lifestyle factors were compared among subgroups stratified by median concentrations of urinary OPFR compounds associated with renal disease severity. This study revealed universal exposure to OPFRs in the CKD population, with an overall urinary detection rate of 98.80 %. Furthermore, after adjusting for covariates, the urinary concentration of bis(2-chloroethyl) phosphate (BCEP) was identified as an independent predictor of lower eGFR (low vs high eGFR, odds ratio (OR) (95 % confidence interval (CI)), 1.761 (1.032–3.005) per log μg/g creatinine, p = 0.038), and the urinary concentration of bis(2-butoxyethyl) phosphate (BBOEP) was independently correlated with overt proteinuria in CKD patients (with vs without overt proteinuria, OR (95 % CI), 1.813 (1.065–3.086) per log μg/g creatinine, p = 0.028). Moreover, frequent seafood consumption was negatively correlated with urinary BCEP concentration (high vs low BCEP, OR (95 % CI), 0.455 (0.228–0.908), p = 0.025), and age was inversely associated with urinary BBOEP concentration (high vs low BBOEP, OR (95 % CI), 0.968 (0.937–0.999) per year, p = 0.048). In conclusion, our investigation highlights the extensive exposure to OPFRs and the independent association between renal disease severity and urinary BCEP/BBOEP concentrations in the CKD population, indicating the nephrotoxic potential of these pollutants.

Associations between organophosphate esters concentrations and markers of liver function in US adolescents aged 12–19 years: A mixture analysis

Liver disease has become a growing health burden, and little is known about the impairment of liver function caused by exposure to organophosphate esters (OPEs) in adolescents aged 12–19 years in the United States. To investigate the relationship between urinary metabolites of OPEs including diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(1-chloroethyl) phosphate (BCPP), bis(2-chloroethyl) phosphate (BCEP), and dibutyl phosphate (DBUP) and liver function in US adolescents aged 12–19 years. Liver function tests (LFTs) include aspartate aminotransferase (AST), albumin (ALB), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin (TBIL), total protein (TP), and AST/ALT. Meanwhile, potential confounding and interaction effects were assessed. The study sample included 592 adolescents aged 12–19 from two consecutive NHANES cycles (2011–2012, 2013–2014). A composite statistical strategy combining traditional linear regression with advanced multi-pollutant models quantile based g-computation (QGC) and eXtreme Gradient Boosting (XGBoost) regression was used to analyze the joint effects of multiple OPEs on liver function indicators, and to describe the interaction between different OPEs in detail. 592 adolescent participants were 15 (14–17) years old, with similar numbers of males and females (304 vs. 288). The analysis results showed that (1) in the linear regression model, individual DPHP, BCEP exposure and ALP changes, BCEP and AST/ALT changes were positively associated. DPHP, BDCPP were negatively associated with TP changes. (2) The combined effects of various OPEs on ALB, ALT, ALP, GGT, TBIL, TP, and AST/ALT were statistically significant. (3) There is no potential interaction between different OPEs. Several OPEs and their combinations are closely related to the 8 LFT indicators. In addition, data suggest that exposure to OPEs in adolescents may be associated with liver damage. Due to limited evidence in the literature and potential limitations of the current study, our findings require more studies to confirm.

Organophosphate ester exposure among Chinese waste incinerator workers: Urinary levels, risk assessment and associations with oxidative stress

Organophosphate esters (OPEs), which are frequently used as flame retardants and plasticizers in versatile products, are readily released to the external environment. Although workers at municipal waste incineration plants may be extensively exposed to OPEs, only scarce health monitoring and risk assessments have been conducted in this population. In this study, we investigated the levels of eight metabolites of organophosphate esters (mOPEs) and the oxidative stress marker 8-hydroxy-2-deoxyguanosine (8-OHdG) in urine samples from 73 waste incinerator workers and 97 general residents from Shenzhen, China between September 2016 and June 2017. The overall detection rate of mOPEs was 82.2 %–100 %, and higher concentrations of di-p-cresyl phosphate and chlorinated mOPEs [bis(2-chloroethyl) phosphate (BCEP), bis(1-chloro-2propyl) phosphate (BCIPP), bis(1,3-dichloro-2-propyl) phosphate) (BDCIPP)] were found among incinerator workers than among general residents. The incinerator workers also showed significantly higher levels of 8-OHdG than general residents, but the measured levels of most mOPEs were not significantly correlated with the level of 8-OHdG; this may be because co-exposure to multiple toxic compounds can lead to oxidative stress. Risk assessment using Monte Carlo simulations revealed that 95 % of the incinerator workers were free from non-carcinogenic effects due to OPEs exposure (hazard index = 0.27, 95 % CI: 0.09, 0.77). However, the carcinogenic risk of tris(2-chloroethyl) phosphate (TCEP) for incinerator workers was between 10−6 and 10−4. These results indicate that incinerator workers are extensively exposed to OPEs, and better protective measures need to be implemented.

Childhood urinary organophosphate esters and cognitive abilities in a longitudinal cohort study

The use of organophosphate esters (OPEs) as flame retardants, which has increased over the past two decades, raises concerns that OPEs may be harmful to humans, especially children. Animal studies and some human studies have reported that OPEs may adversely impact brain development, but few human studies evaluated OPE exposure during early childhood and neurodevelopmental outcomes. We aimed to fill this knowledge gap with the present study on urinary OPE metabolite concentrations at ages 1–5 years and cognitive abilities at 8 years. We used data of 223 children from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio. The point estimates for bis-2-chloroethyl-phosphate (BCEP) and bis(1,3-dichloro-2-propyl)-phosphate (BDCIPP) in association with IQ tended to be small and positive, while the point estimates for diphenyl-phosphate (DPHP) were small and negative, with 95% CIs including the null. However, we did find that socioeconomic status (SES) variables modified associations between OPEs and child IQ, with adverse OPE-IQ associations being stronger in socioeconomically disadvantaged children than in others. We identified an additional 1- to 2-point decrease in Full Scale IQ for every log-unit increase in BDCIPP, BCEP, and DPHP among those with lower maternal education, non-white race, lower income, or living in more deprived neighborhoods. We observed similar results for the Perceptual Reasoning, Verbal Comprehension, and Working Memory Index Scores. We suspect that there is residual confounding related to socioeconomic disadvantage, which was not captured with the available SES variables typically used in epidemiologic studies.

Early life organophosphate ester exposures and bone health at age 12 years: The Health Outcomes and Measures of the Environment (HOME) Study

BackgroundNo human studies have evaluated early life organophosphate ester (OPE) exposures with bone health outcomes, despite evidence of osteotoxicity. ObjectivesWe assessed associations of urinary OPE metabolites measured across early life with areal bone mineral density (aBMD) and bone mineral content (BMC) at age 12 years. MethodsAmong 223 mother-child dyads enrolled in the Health Outcomes and Measures of the Environment (HOME) Study, we quantified concentrations of bis-2-chloroethyl phosphate (BCEP), bis-(1,3-dichloro-2-propyl) (BDCIPP), di-n-butyl phosphate (DnBP), and diphenyl phosphate (DPHP) in urine collected from mothers during pregnancy and children at ages 1, 2, 3, 5, and 8 years. At age 12 years, we performed dual energy x-ray absorptiometry and calculated aBMD and BMC z-scores at six skeletal sites. We estimated overall and sex-stratified BMD/BMC z-score differences per interquartile range (IQR) increase in OPE concentrations at multiple exposure timepoints: gestation (average) and 1–3 (average), 5, and 8 years. ResultsIn adjusted models, overall associations of BCEP and BDCIPP with total hip and 1/3rd distal radius aBMD and BMC varied significantly by exposure timepoint, as did BDCIPP with whole body aBMD. For example, differences (95 % CI) in total hip aBMD z-score per IQR increase in BDCIPP were 0.33 (0.01, 0.64), −0.10 (−0.34, 0.14), −0.18 (−0.40, 0.05), and 0.14 (−0.09, 0.38) for concentrations during gestation and at 1–3, 5, and 8 years, respectively. Overall DnBP and DPHP associations were generally null at all timepoints. We observed sex-specific associations for some timepoints and skeletal sites. For example, an IQR increase in 8-year DPHP was associated with a 0.21 (0.05, 0.38) greater total hip aBMD z-score among females but −0.19 (−0.43, 0.05) lower z-score among males. DiscussionEarly life OPE exposures may be associated with sex- and exposure period-dependent alterations in early adolescent bone mineral accrual and strength.

Association between organophosphorus flame retardants exposure and cognitive impairment among elderly population in southern China

The wide application of organophosphorus flame retardants (OPFRs) in consumer products leads to their ubiquitous occurrence. The neurotoxicity of OPFRs has been raised, whereas evidence from the elderly population were rather scarce. Hence, a case-control study was conducted based on the Shenzhen Aging-related Disorder Cohort. A total of 184 cases [Mini-mental State Examination (MMSE) < 24] and 795 participants as controls (MMSE ≥24) were recruited. Eight metabolites of OPFRs (m-OPFRs) in urine samples were measured, including bis(2-butoxyethyl) phosphate (BBOEP), bis(2-chloroethyl) phosphate (BCEP), bis(1-chloro-2-propyl) phosphate (BCIPP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), dibutyl phosphate (DBP), di-o-cresyl phosphate (DOCP), di-p-cresyl phosphate (DPCP) and diphenyl phosphate (DPHP). The detection frequencies of m-OPFRs ranged from 88.8 % to 95.4 %. BCEP had the highest median concentration (0.93 μg/L), followed by BCIPP (0.32 μg/L), DPHP (0.27 μg/L) and DBP (0.20 μg/L). Significant correlations were found between all pairs of urinary m-OPFRs with correlation coefficients ranging from 0.22 to 0.71 (p< 0.05). Logistic regression models showed that urinary concentrations of BDCIPP (adjusted odds ratio [OR]: 1.25, 95 % confidential interval [CI]: 1.04–1.50) and DBP (adjusted OR: 1.10, 95 % CI: 1.01–1.20) were positively associated with lower cognitive functions. Furthermore, a nonlinear dose-response relationship was found between urinary BDCIPP concentration and cognitive decline. To our knowledge, this is the first report on OPFR exposure and cognitive impairment among elderly population. Further toxicological tests of BDCIPP and DBP are needed to illustrate these results.

Associations between organophosphate esters metabolites and sleep disorder and trouble sleeping in adults: a machine-learning approach.

Organophosphate esters (OPEs) are used widely as flame retardants and plasticizers. However, the associations between OPEs metabolites and sleep outcomes (sleep disorder and trouble sleeping) remain unknown. Data utilized in this cross-sectional study was from the National Health and Nutrition Examination Survey 2013-2014, including 1393 adults aged ≥ 20years. We conducted weighted logistic regression and Bayesian kernel machine regression (BKMR) models to analyze the associations between OPEs metabolites and sleep outcomes. We included data from 2011 to 2012 cycle in our sensitivity analysis to explore the association further. Logistic regression model presented a significant positive association between diphenyl phosphate (DPHP) and sleep disorder in all participants (odds ratio (95% confidence interval) for the second quartile was 2.46 (1.85, 3.28)). We observed positive associations between OPEs metabolites and sleep outcomes in males. Among females, no significant association was observed in the logistic model. BKMR presented that dibutyl phosphate (DBUP) was the relatively important exposure. There was a positive association between OPEs metabolites mixture and trouble sleeping. Univariable exposure-response functions demonstrated U-shaped associations between DBUP and sleep outcomes, while bis(2-chloroethyl) phosphate (BCEP) was associated with sleep disorder negatively in females. No substantial changes appeared in the results after including the data from 2011 to 2012 cycle. This current study indicated that OPEs metabolites might be associated with sleep disorder and trouble sleeping, and the associations seemed to be sex-dependent.

Rhizobiales as the Key Member in the Synergistic Tris (2-chloroethyl) Phosphate (TCEP) Degradation by Two Bacterial Consortia

Tris(2-chloroethyl) phosphate (TCEP) is of growing concern because of its ubiquitous occurrence, potential toxicity, and persistence in the environment. In this study, two efficient TCEP degradation consortia (AT1 and AT3) were developed and were able to completely hydrolyze TCEP within 20-25 h. Rhizobiales was identified as the key degrader in both consortia, because Rhizobiales-related phosphoesterase genes were enriched by one to two orders of magnitude when the carbon source was changed from acetate to TCEP. In addition, the increase in Rhizobiales abundance was related to the development of TCEP degradation. The isolation of Xanthobacter strains confirmed the efficient TCEP and bis(2-chloroethyl) phosphate (BCEP) degradation of Rhizobiales. The higher abundances of phosphoesterase genes affiliated with Rhizobiales genera (Bradyrhizobium and Ancylobacter), Cytophagales genus (Spirosoma), Sphingobacteriales genus (Pedobacter), and Burkholderia genus (Methylibium), may be related to the faster TCEP degradation in AT3, while the higher abundance of Rhizobiales genus (Hyphomicrobium)-related phosphodiesterase (PDE) genes may contribute to the faster BCEP degradation in AT1. The stepwise hydrolysis of TCEP was likely catalyzed by different bacterial guilds, which was confirmed by the coculture of TCEP- and BCEP-degrading isolates and highlighted the importance of synergistic interactions during TCEP degradation.

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.

Association of urinary organophosphate esters level with sex steroid hormones levels in adult males: A nationwide study, NHANES 2013-2014.

Exposure to environmental pollution via different mechanisms is associated with multiple endocrine dysfunctions. Organophosphate esters (OPEs) are endocrine-disrupting chemicals that affect sex steroid hormones. We aimed to study the effect of OPEs and their metabolites, such as diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(2-chloroethyl) phosphate (BCEP), and dibutyl phosphate (DBUP), on sex steroid hormones in males. This cross-sectional analytical study analyzed data from the 2013-2014 National Health and Nutrition Examination Survey among 763 male participants aged ≥20 years. The relationships between the metabolites of OPEs and total testosterone, estradiol, sex hormone-binding globulin, and the ratio of total testosterone to estradiol (a parameter derived from total testosterone and estradiol) were evaluated using multivariate linear regression models that were adjusted for potential confounders. A total of 763 participants, with a mean age of 44.59 (±15.59) years, were enrolled. Of these, 65.7% participants had non-Hispanic white ancestry, 9.83% had non-Hispanic black ancestry, and 15.97% had Hispanic ancestry. Participants with higher urinary level of DPHP had a lower level of total testosterone and estradiol. Moreover, higher urinary levels of BDCPP were associated with higher estradiol. According to our study, which is based on a representative population of US adults, exposure to OPEs was significantly associated with altered sex hormone levels (total testosterone and estradiol). Further studies focused on the underlying mechanisms regarding the association between each metabolite and sex steroid hormones are required.

Maternal urinary OPE metabolite concentrations and blood pressure during pregnancy: The HOME study

BackgroundFew studies have examined the association between maternal exposure to organophosphate esters (OPEs) and systolic/diastolic blood pressure (SBP/DBP) during pregnancy. MethodsWe analyzed data from 346 women with a singleton live birth in the HOME Study, a prospective birth cohort in Cincinnati, Ohio, USA. We quantified four OPE metabolites in maternal spot urine samples collected at 16 and 26 weeks pregnancy, standardized by specific gravity. We calculated intraclass correlation coefficients (ICCs). We extracted the first two recorded BP measurements (<20 weeks), the two highest recorded BP measurements (≥20 weeks), and diagnoses of hypertensive disorders of pregnancy (HDP) via chart review. Women with two BP measurements ≥140/90 mmHg or HDP noted in the chart at ≥20 weeks pregnancy were defined as HDP cases. We used linear mixed models and modified Poisson regression with covariate adjustment to estimate associations between OPE concentrations as continuous variables or in tertiles with maternal BP and HDP. ResultsICCs of OPEs were 0.17–0.45. Diphenyl phosphate (DPHP) had the highest geometric mean concentration among OPE metabolites. Increasing the average bis(2-chloroethyl) phosphate (BCEP) concentrations were positively associated with two highest recorded DBP ≥20 weeks pregnancy. Compared with women in the 1st DPHP tertile, women in the 3rd tertile at 16 weeks pregnancy had 1.72 mmHg (95% CI: -0.01, 3.46) higher DBP <20 weeks pregnancy, and women in the 3rd tertile of the average DPHP concentrations had 2.25 mmHg (95% CI: 0.25, 4.25) higher DBP ≥20 weeks pregnancy. 33 women (9.5%) were identified with HDP. Di-n-butyl phosphate (DNBP) concentrations at 16 weeks were positively associated with HDP, with borderline significance (RR = 2.98, 95% CI 0.97–9.15). Other OPE metabolites were not significantly associated with HDP. ConclusionMaternal urinary BCEP and DPHP concentrations were associated with increased BP during pregnancy. Maternal urinary DNBP concentrations were associated with HDP, with borderline significance.

Prenatal exposure to a mixture of organophosphate esters and intelligence among 8-year-old children of the HOME Study

Many environmental chemicals are being identified as suspected neurotoxicants based on the findings of both experimental and epidemiological studies. Organophosphate esters (OPEs), which are among the chemicals that have replaced neurotoxic polybrominated diphenyl ethers (PBDEs) after 2004, have also become an important public health topic as evidence regarding their potential for early-life neurotoxicity is growing. In 233 mother child pairs from Cincinnati, OH, we measured concentrations of the OPE metabolites bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis-2-chloroethyl phosphate (BCEP), diphenyl phosphate (DPHP), and di-n-butyl phosphate (DNBP) in the urine of pregnant women at 16 and 26 weeks gestation and at delivery. At age 8 years, we assessed children’s cognition using the Wechsler Intelligence Scale for Children-IV. In models adjusted for maternal race, income, body mass index, and IQ, maternal urinary BCEP was associated with a modest increase in child full-scale IQ (ß: 0.81 per a ln-unit BCEP increase; 95 % CI: 0.00, 1.61) while other OPEs were not associated with changes in full-scale IQ or any IQ subscales. Maternal serum PBDE concentrations did not confound the relationships between urinary OPE metabolites and child IQ. Using Bayesian kernel machine regression, we did not find that concentrations of a mixture of OPE metabolites during gestation was associated with any child cognition measures. The results of this study are not consistent with other published work, and a larger sample size would be beneficial to explore potential associations more fully. Therefore, additional studies are necessary to continue studying prenatal OPE exposure and child neurodevelopment and behavior.

The associations between organophosphate esters and urinary incontinence in the general US population

Organophosphate esters (OPEs) impact health in many ways. Since its relationship with urinary incontinence remains unknown, we aimed to explore their associations in the US general population. We combined the results of urine specimens test and self-reported urinary incontinence conditions from the National Health and Nutrition Examination Survey (NHANES) 2013–2014 among 2666 participants and then conducted linear regression and logistic regression to analyse associations between log2-transformed OPE concentrations and urinary incontinence. We found that 0.92% of men and 15.74% of women complained of mixed urinary incontinence (MUI). The concentrations of diphenyl phosphate (DPHP) were significantly correlated to MUI among women when treated as a continuous variable (adjusted odds ratio (OR) = 1.15; 95% confidence interval (CI), 1.01–1.31; p = 0.0369) and as a categorical variable (adjusted OR = 1.24; 95% CI, 1.03–1.49; p for trend = 0.0245), whereas no positive correlation was found in males. There were no significant associations between the other three OPEs: bis(2-chloroethyl) phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and dibutyl phosphate (DBUP). The association of DPHP with an increased prevalence OR of MUI in women is a public health concern; future prospective studies are needed to explore its potential mechanism.

Associations between polyfluoroalkyl substance and organophosphate flame retardant exposures and telomere length in a cohort of women firefighters and office workers in San Francisco

BackgroundEnvironmental chemical exposures can affect telomere length, which in turn has been associated with adverse health outcomes including cancer. Firefighters are occupationally exposed to many hazardous chemicals and have higher rates of certain cancers. As a potential biomarker of effect, we assessed associations between chemical exposures and telomere length in women firefighters and office workers from San Francisco, CA.MethodsWe measured serum concentrations of polyfluoroalkyl substances (PFAS), urinary metabolites of flame retardants, including organophosphate flame retardants (OPFRs), and telomere length in peripheral blood leukocytes in women firefighters (N = 84) and office workers (N = 79) who participated in the 2014–15 Women Workers Biomonitoring Collaborative. Multiple linear regression models were used to assess associations between chemical exposures and telomere length.ResultsRegression results revealed significant positive associations between perfluorooctanoic acid (PFOA) and telomere length and perfluorooctanesulfonic acid (PFOS) and telomere length among the whole cohort. Models stratified by occupation showed stronger and more significant associations among firefighters as compared to office workers. Among firefighters in models adjusted for age, we found positive associations between telomere length and log-transformed PFOA (β (95%CI) = 0.57(0.12, 1.02)), PFOS (0.44 (0.05, 0.83)), and perfluorodecanoic acid (PFDA) (0.43 (0.02, 0.84)). Modeling PFAS as categories of exposure showed significant associations between perfluorononanoic acid (PFNA) and telomere length among firefighters. Significant associations between OPFR metabolites and telomere length were seen for bis (1,3-dichloro-2-propyl) phosphate (BDCPP) and telomere length among office workers (0.21(0.03, 0.40)) and bis (2-chloroethyl) phosphate (BCEP) and telomere length among firefighters (− 0.14(− 0.28, − 0.01)). For OPFRs, the difference in the direction of effect by occupational group may be due to the disparate detection frequencies and concentrations of exposure between the two groups and/or potential unmeasured confounding.ConclusionOur findings suggest positive associations between PFAS and telomere length in women workers, with larger effects seen among firefighters as compared to office workers. The OPFR metabolites BDCPP and BCEP are also associated with telomere length in firefighters and office workers. Associations between chemical exposures and telomere length reported here and by others suggest mechanisms by which these chemicals may affect carcinogenesis and other adverse health outcomes.

Organophosphate and organohalogen flame retardant exposure and thyroid hormone disruption in women firefighters and office workers from San Francisco

BACKGROUND AND AIM: Organophosphate flame retardants (OPFR) are suspected endocrine disrupting compounds and have been detected in fire station dust and firefighter gear. Studies have reported that exposure to FRs can disrupt thyroid hormone (TH) function; however, this relationship is not well characterized, especially for halogenated OPFRs. TH is important for thyroid mediated gene expression and may be relevant to adverse health effects such as cardiovascular disease and cancer. We describe OPFR exposure and its association with TH levels in a cohort of women firefighters and office workers from San Francisco. METHODS: Using liquid chromatography-tandem mass spectrometry (LC MS/MS), we measured 8 urinary FR metabolites in female firefighters (N=86) and office workers (N=84) from San Francisco: bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(2-chloroethyl) phosphate (BCEP), dibutyl phosphate (DBuP), dibenzyl phosphate (DBzP), di-p-cresyl phosphate (DpCP), di-o-cresyl phosphate (DoCP), 2,3,4,5-tetrabromobenzoic acid (TBBA), tetrabromobisphenol-A (TBBPA). We assessed potential predictors of exposure levels and the association between FR exposures and thyroxine (T4) and thyroid stimulating hormone (TSH) for 84 Firefighters and 81 office workers. RESULTS:BDCPP, BCEP and DBuP had the highest concentrations among all study participants. However, firefighters had higher median exposure levels of BDCPP, BCEP and DBuP compared to office workers. When we assessed the association of each FR with TH we found that a doubling of BDCPP was associated with a 2.88% decrease (95%CI -5.28,-0.42) in T4 among firefighters. We did not observe significant associations between FR and T4 among office workers nor between FR and TSH in either firefighters or office workers. CONCLUSIONS:Firefighters had significantly higher exposures to FR compared to office workers and their exposure to BDCPP was associated with TH disruption. Characterizing exposure to endocrine disrupting chemicals and assessing the association with biomarkers of early effect such as TH can inform prevention efforts without having to wait for adverse health outcomes to occur. KEYWORDS: occupational exposures, women firefighters, endocrine disruption