Organophosphate Esters Metabolites Research Articles

Association between organophosphate esters exposure and all-cause and cause-specific mortality: a national population-based cohort study

ABSTRACT Exposure to organophosphate esters (OPEs) is associated with several chronic diseases, but the relationship with mortality risk is unclear. Therefore, we used the National Health and Nutrition Examination Survey 2011–2018 data to evaluate these relationships. 6,869 participants aged 18 years or older were included. Survival status information was obtained through the National Death Index through 31 December 2019. Multivariable COX regression model was adopted to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationships of urinary OPEs metabolites with mortality risk. During an average of 5.0 years of follow-up, 406 deaths were documented. After adjusting for confounders, bis(2-chloroethyl) phosphate was associated with an increased risk of all-cause mortality [HR (95%CI) = 1.12(1.05–1.20)] and cardiovascular mortality [HR (95%CI) = 1.15(1.04–1.26)]. Our study found that exposure to OPEs was significantly associated with increased risks of all-cause and cardiovascular mortality. Consequently, controlling OPEs exposure is needed to alleviate the health-related burden.

Organophosphate ester flame retardant chemicals and maternal depression during pregnancy

BackgroundDepression substantially contributes to pregnancy-related morbidity, and pregnancy is increasingly recognized as a vulnerable window for exposure effects on maternal mental health. Exposures to organophosphate esters (OPEs) are ubiquitous and may have neurotoxic effects; however, their impacts on prenatal depression remain unknown. We evaluated associations of third trimester OPE metabolites on maternal depressive symptoms during pregnancy. MethodsThis study included 422 participants in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort, a prospective pregnancy cohort of primarily low-income and Hispanic participants residing in Los Angeles, California. We measured concentrations of nine OPEs in third trimester spot urine samples (mean gestational age = 31.5 ± 2.0 weeks). Using the Center for Epidemiologic Studies-Depression (CES-D) scale, we classified participants as having probable depression during pregnancy (N = 137) or not (N = 285) if one or more CES-D scores administered at each trimester met the suggested cutoff score for clinically significant depressive symptoms (≥16). We estimated associations of prenatal OPE metabolite concentrations in tertiles and risk of prenatal depression using modified Log-Poisson regression. We examined associations of the OPE mixture on depression during pregnancy using Bayesian kernel machine regression (BKMR). ResultsParticipants with the highest tertiles of DPHP and BDCIPP exposure had a 67% (95% CI: 22%, 128%) and 47% (95% CI: 4%, 108%) increased risk of maternal depressive symptoms during pregnancy, respectively. No associations between other OPE metabolites and maternal depression symptoms were observed. In mixture analyses, we observed a positive and linear association between higher exposure to the OPE metabolite mixture and odds of prenatal maternal depression, primarily driven by DPHP. ConclusionsOur findings provide new evidence of associations between frequently detected OPE metabolites on maternal depression symptoms during pregnancy. Results could inform future intervention efforts aimed at reducing perinatal maternal depression.

Gestational organophosphate esters (OPEs) exposure in association with placental DNA methylation levels of peroxisome proliferator-activated receptors (PPARs) signaling pathway-related genes

BackgroundOrganophosphate esters (OPEs) exposure could affect offspring health. However, the underlying mechanisms are not well documented. ObjectivesBased on a birth cohort study, we aimed to investigate the associations among gestational OPEs exposure, placental DNA methylation levels of peroxisome proliferator-activated receptor (PPAR) signaling pathway-related genes, and fetal growth. MethodsWe measured the concentrations of eight OPE metabolites in maternal urine samples and neonatal anthropometric measurements in 733 mother-child pairs. In 327 placental samples, we assessed the DNA methylation levels of 14 genes which were involved in the PPARs signaling pathway and expressed in placenta. Multiple linear regression models were used to examine the associations of OPEs exposure with placental DNA methylation, and of OPEs and placental DNA methylation with neonatal anthropometric measurements. Causal mediation analyses were conducted to examine the potential mediating role of placental DNA methylation in the pathway between OPEs exposure and fetal growth. ResultsWe observed a general pattern of OPEs exposure being associated with hypermethylation of candidate genes, with statistically significant associations identified for several OPEs with RXRA, ACAA1, ACADL, ACADM, PLTP, and NR1H3 methylation. Further, gestational exposure to BCIPP, DPP, BBOEP, ∑NCl-OPEs, and ∑OPEs tended to be associated with lower anthropometric measurements, with more significant associations observed on arm circumference, and abdominal and back skinfold thickness. Notably, RXRA, ACAA1, ACOX1, CPT2, ACADM, and NR1H3 methylation tended to be associated with lower neonatal anthropometric measurements, especially for abdominal and back skinfold thickness. Moreover, mediation analyses showed that 19.42 % of the total effect of DPP on the back skinfold thickness was mediated by changes in RXRA methylation, and there was a significant indirect effect of RXRA methylation. ConclusionsGestational OPEs exposure could disrupt the placental DNA methylation levels of PPAR signaling pathway-related genes, which might contribute to the effect of OPEs on fetal growth.

Estimated daily intake and cumulative risk assessment of organophosphate esters and associations with DNA damage among e-waste workers in Hong Kong

Organophosphate esters (OPEs) are extensively used as additives in various products, including electronic equipment, which becomes e-waste when obsolete. Nevertheless, no study has evaluated OPEs exposure levels and the related health risks among e-waste workers in Hong Kong. Therefore, 201 first-spot morning urine samples were collected from 101 e-waste workers and 100 office workers to compare eight urinary OPE metabolites (mOPEs) levels in these groups. The concentrations of six mOPEs were similar in e-waste workers and office workers, except for significantly higher levels of diphenyl phosphate (DPHP) in e-waste workers and bis(1-chloro-2propyl) phosphate (BCIPP) in office workers. Spearman correlation analysis showed that most non-chlorinated mOPEs were correlated with each other in e-waste workers (i.e., nine out of ten pairs, including di-p-cresyl phosphate (DpCP) and di-o-cresyl phosphate (DoCP), DpCP and bis(2-butoxyethyl) phosphate (BBOEP), DpCP and DPHP, DpCP and dibutyl phosphate (DBP), DoCP and BBOEP, DoCP and DPHP, DoCP and DBP, BBOEP and DPHP, DPHP and DBP), indicating that handling e-waste could be the exposure source of specific OPEs. The median values of estimated daily intake (EDI) and hazard quotient (HQ) suggested that the health risks from OPEs exposures were under the recommended thresholds. However, linear regression models, Quantile g-computation, and Bayesian kernel machine regression found that urinary mOPEs elevated 8-hydroxy-2-deoxyguanosine (8-OhdG) levels individually or as a mixture, in which DPHP contributed prominently. In conclusion, although e-waste might not elevate the internal OPEs levels among the participating Hong Kong e-waste workers, attention should be paid to the potential DNA damage stimulated by OPEs under the currently recommended thresholds.

Biomarkers of Organophosphate and Polybrominated Diphenyl Ether (PBDE) Flame Retardants of American Workers and Associations with Inhalation and Dermal Exposures.

This study evaluated workers' exposures to flame retardants, including polybrominated diphenyl ethers (PBDEs), organophosphate esters (OPEs), and other brominated flame retardants (BFRs), in various industries. The study aimed to characterize OPE metabolite urinary concentrations and PBDE serum concentrations among workers from different industries, compare these concentrations between industries and the general population, and evaluate the likely route of exposure (dermal or inhalation). The results showed that workers from chemical manufacturing had significantly higher (p <0.05) urinary concentrations of OPE metabolites compared to other industries. Spray polyurethane foam workers had significantly higher (p <0.05) urinary concentrations of bis(1-chloro-2-propyl) phosphate (BCPP) compared to other industries. Electronic scrap workers had higher serum concentrations of certain PBDE congeners compared to the general population. Correlations were observed between hand wipe samples and air samples containing specific flame-retardant parent chemicals and urinary metabolite concentrations for some industries, suggesting both dermal absorption and inhalation as primary routes of exposure for OPEs. Overall, this study provides insights into occupational exposure to flame retardants in different industries and highlights the need for further research on emerging flame retardants and exposure reduction interventions.

Investigation of Urinary Metabolites of Organophosphate Esters in Hanoi, Vietnam: Assessment Exposure and Estimated Daily Intake.

In recent years, organophosphate esters (OPEs) have become one of the most common additives in various consumer products worldwide, therefore the exposure and impact of OPEs on human health are drawing a lot of attention. In this study, three metabolites of OPEs including bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPhP) and diethyl phosphate (DEP) were investigated in first-morning void urine samples taken from a population (age range: 3-76years old) in Hanoi, Vietnam. The most dominant urinary OPE metabolite was DEP with the geometric mean of specific gravity adjust (SG-adjusted) concentration were 1960ngmL-1 and detected frequency (DF) of 98%. Followed by DPhP (8.01ngmL-1, DF: 100%) and BDCIPP (2.18ngmL-1, DF: 51%). The results indicated that gender and age might have associations with the OPE metabolites variation in urine samples. The levels of OPE metabolites in urine samples from females were slightly higher than in males. An increase in age seems to have an association with a decrease in DPhP levels in urine. Exposure doses of parent OPEs were evaluated from the unadjusted urinary concentration of corresponding OPE metabolite. The estimated exposure doses of triethyl phosphate (TEP) (mean: 534,000ngkg-1d-1) were significantly higher than its corresponding reference dose, suggesting the high potential risk from the current exposure doses of TEP to human health. The results of this work provided the initial information on the occurrence of three OPE metabolites in urine from Hanoi, Vietnam and estimated exposure dose of corresponding parent OPEs.

Short term temporal variability of selected organophosphate esters among healthy adults living in the National Capital Region of Canada

Organophosphate esters (OPEs) are used primarily as flame-retardants and plasticizers. OPEs are commonly detected in various environmental matrices, food and drinking water, and their metabolites are frequently found and quantified in urine. Potential adverse impacts on human health, including carcinogenicity, neurotoxicity, developmental and reproductive toxicity have been well documented. Urinary concentration of OPE metabolites can vary in the same individual, depending on the sampling time, thus introducing significant uncertainty in exposure assessment. The current study focusses on the assessment of short term temporal variability in adult men and women residing in Canada's Capital Region. Fifteen OPE metabolites were analyzed in 562 daily urine samples, collected every three days for five weeks from 11 volunteers. Sample extraction procedure was performed on an automated SPE and extracts analyzed using UPLC-MS/MS. In spot urine samples as well as first morning void (FMV), the detection frequency was greater than 50% for bis (2-chloroethyl) hydrogen phosphate (BCEP), bis (1-chloro-2-propyl) phosphate (BCIPP), bis (1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP) and bis(2,4-ditert-butylphenyl) hydrogen phosphate (B2,4DtBPP). Significant difference was observed in males and females for BCEP and BCIPP. Intra-class correlation coefficient (ICC) for creatinine corrected data for the spot urine samples ranged from 0.37 to 0.69. Good reproducibility was observed for creatinine corrected DPHP and BCIPP in both spot urine and FMV samples. More variation was observed between study participants in the spot urine samples when compared to the FMV samples. However, when considering diurnal difference there was a considerable inter-day variation in the FMV samples compared to the spot samples. The strength of the study is that the participants belonged to the same geographical location and working in the same facility, hence spatial variability did not influence the outcome of the results.

Trimester-specific effect of maternal co-exposure to organophosphate esters and phthalates on preschooler cognitive development: The moderating role of gestational vitamin D status

Organophosphate esters (OPEs) and phthalate acid esters (PAEs) are prevalent endocrine-disrupting chemicals (EDCs). Humans are often exposed to OPEs and PAEs simultaneously through multiple routes. Given that fetal stage is a critical period for neurodevelopment, it is necessary to know whether gestational co-exposure to OPEs and PAEs affects fetal neurodevelopment. However, accessible epidemiological studies are limited. The present study included 2, 120 pregnant women from the Ma'anshan Birth Cohort (MABC) study. The concentrations of tris (2-chloroethyl) phosphate (TCEP), 6 OPE metabolites and 7 PAE metabolites were measured in the first, second and third trimester using ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS). Cognitive development of preschooler was assessed based on the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) of the Chinese version. Generalized estimating equations (GEEs), restricted cubic spline (RCS) and generalized additive models (GAMs) were employed to explore the associations between individual OPE exposure and preschooler cognitive development. The quantile-based g-computation (QGC) method was used to estimate the joint effect of PAEs and OPEs exposure on cognitive development. GEEs revealed significant adverse associations between diphenyl phosphate (DPHP) (β: −0.58, 95% CI: −1.14, −0.01), bis (2-butoxyethyl) phosphate(BBOEP) (β: −0.44, 95% CI: −0.85, −0.02), bis(1-chloro-2-propyl) phosphate (BCIPP) (β: −0.81, 95%CI: −1.43, −0.20) and full-scale intelligence quotient (FSIQ) in the first trimester; additionally, TCEP and bis(2-ethylhexyl) phosphate (BEHP) in the second trimester, as well as DPHP in the third trimester, were negatively associated with cognitive development. Through the QGC analyses, mixture exposure in the first trimester was negatively associated with FSIQ scores (β: −1.70, 95% CI: −3.06, −0.34), mono-butyl phthalate (MBP), BCIPP, and DPHP might be the dominant contributors after controlling for other OPEs and PAEs congeners. Additionally, the effect of OPEs and PAEs mixture on cognitive development might be driven by vitamin D deficiency.

Assessment of Human Exposure to Traditional and Novel Organophosphate Esters via Multiple Personal Matrices.

Herein, 16 traditional and 13 novel organophosphate esters (OPEs) in skin wipes, personal PM2.5, sputum, and nails (fingernails and toenails) and 7 OPE metabolites in urine synchronously obtained from 64 college students were analyzed. Similar compositional profiles of the OPEs were found in skin wipes and nails and in personal PM2.5 and induced sputum. Significant correlations were observed between the concentrations of high-lipophilicity low-volatility OPEs in skin wipes and nails and between the concentrations of high-volatility low-lipophilicity OPEs in personal PM2.5 and sputum. These results imply that OPEs in fingernails and toenails may mainly come from external sources rather than internal exposure, and human nails and sputum can be used as indicators of human exposure to OPEs. A comparison between the daily exposure doses of the OPEs in personal PM2.5 and sputum shows that more volatile compounds may have higher inhalation bioavailability, which should be considered to improve the accuracy of inhalation exposure assessments. According to comprehensive external and internal exposure assessment, dermal absorption may be a more dominant pathway than inhalation, and skin wipes may be the best representative environmental matrix of human exposure to OPEs.

Occurrence and removal of legacy plasticizers and flame retardants through a drinking water treatment plant

The occurrence of thirty-four flame retardants and plasticizers throughout treatment steps in a drinking water treatment plant (DWTP) was analyzed to assess removal efficiencies of filtration, ultraviolet (UV) treatment, and chlorination. Legacy compounds and replacements were included to compare their presence and persistence. Twenty-four-hour composite sampling, offset to account for retention time, was performed at a direct filtration DWTP in Montreal, Canada over a three-day period. Polybrominated diphenyl ethers (PBDEs), considered legacy flame retardants, were infrequently detected or at concentrations <1 ng/L. When overall removal efficiencies could be calculated, the removal of ∑7PBDEs was 49 and 94 % for days 2 and 3, respectively. No removal could be calculated on day 1 as PBDEs were only detected in finished drinking water. Higher brominated PBDEs BDE-183 and BDE-154 were only detected in raw water. Organophosphate esters (OPEs), considered replacement flame retardants, were frequently detected in all water samples. The total average concentration of ∑15OPes was 501 ng/L in raw water and 162 ng/L in drinking water, with an average removal efficiency of 67 %. OPEs were mainly removed during filtration, with TCIPP, TDCIPP, and TPHP showing statistically significant removal of 76, 84, and 95 %, respectively. The total average concentration of ∑8plasticizers was 2938 ng/L in raw water and 116 ng/L in drinking water. All plasticizers, except for metabolite MEHP, had significant removal from filtration, and the overall removal of plasticizers ranged from 20 % for DEP to 99 % for DEHP. Drinking water treatment decreases the concentration of these contaminants in drinking water but was less effective in removing flame retardants than plasticizers, as indicated by their higher number of PBDEs detected and higher concentrations of OPEs measured. To our knowledge, it is the first report of the removal of PBDEs, OPE metabolites and plasticizer replacements (DEHA, DIDA, DINCH, DINP) during drinking water treatment.

Prenatal exposures to organophosphate ester metabolites and early motor development in the MADRES cohort

Organophosphate esters (OPEs) are increasingly considered neurotoxicants which may impact gross and fine motor development. We evaluated associations between prenatal OPE exposures and infant motor development. Third trimester urinary concentrations of nine OPE metabolites were measured in 329 mother-infant dyads participating in the Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) cohort. Child gross and fine motor development at 6, 9, 12, and 18-months were assessed with the Ages and Stages Questionnaire-3 (ASQ-3) and operationalized in models using dichotomous instrument-specific cutoffs for typical motor development. Five OPE metabolites with >60% detection were specific-gravity-adjusted, natural log-transformed, and modeled continuously, while four metabolites with <60% detection were modeled dichotomously (detected/not-detected). We fit mixed effects logistic regression between OPE metabolites and fine/gross motor development and assessed sex-specific effects using a statistical interaction term and sex-stratified models. Among children, 31% and 23% had gross and fine motor scores, respectively, below the ASQ-3 at-risk cutoffs at least once across infancy. A doubling in prenatal diphenyl phosphate (DPHP) exposure was associated with 26% increased odds of potential fine motor delays (ORfine = 1.26, 95% CI: 1.02, 1.57, p = 0.04). We also observed significant interactions by infant sex for associations of detected dipropyl phosphate (DPRP) with gross motor development (pinteraction = 0.048) and detected bis(1-chloro-2-propyl) phosphate (BCIPP) with fine motor development (pinteraction = 0.02). Females had greater odds of potential motor delays for both detected DPRP (females vs males ORgross (95% CI) = 1.48 (0.71, 3.09), p = 0.30 vs 0.27 (0.06, 1.29), p = 0.10) and detected BCIPP (females vs males ORfine (95% CI) = 2.72 (1.27, 5.85), p = 0.01 vs 0.76 (0.31, 1.90), p = 0.56). There were no other significant associations between other metabolites and motor development, despite similar patterns. We found evidence of adverse effects of prenatal OPE exposures on infant motor development with greater adverse effects among female infants with some OPE metabolites.

Prenatal exposure to organophosphate esters and growth trajectory in early childhood

Maternal exposure to organophosphate esters (OPEs) has been linked to an increased risk of adverse birth outcomes. However, the impact of OPEs on childhood growth remains uncertain. This study assessed the associations between prenatal concentrations of OPE metabolites and the growth trajectory in early childhood. 212 singleton pregnant women were included in this study, and they were recruited between August 2014 and August 2016 in Wuhan, China. We measured the urinary concentrations of OPE metabolites during the 1st, 2nd, and 3rd trimesters. Standard deviation scores for weight and length were calculated for children at birth, 1, 6, 12, and 24 months. Trajectories of weight-for-age z-score (WAZ) and weight-for-length z-score (WLZ) were classified into four groups using group-based trajectory modeling. Trajectories of length-for-age z-score (LAZ) were classified into three groups with the same model. Then, we calculated odds ratios (ORs) and 95 % confidence interval (95%CI) using multinomial logistic regression to estimate increases in odds of different growth trajectories per doubling in OPE concentrations compared with moderate-stable trajectory. For average concentrations of OPE metabolites and growth trajectory, our results indicated that higher bis(2-butoxyethyl) phosphate, total aromatic OPE metabolites, and total OPE metabolites during pregnancy were associated with a higher likelihood of children falling into the low-stable and low-rising WAZ trajectory. Furthermore, compared to the moderate-stable LAZ trajectory, increased concentrations of 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate were linked to an elevated risk of a low-stable LAZ trajectory. Additionally, the 1st and 2nd trimesters may represent critical windows of heightened vulnerability to the effects of OPE metabolites on childhood growth. In conclusion, our study proves that prenatal exposure to OPE metabolites is inversely related to childhood growth. It is essential to conduct further research involving larger populations and to consider other compounds with known developmental toxicity to obtain more reliable and comprehensive results.

Associations between exposure to organophosphate esters and overactive bladder in U.S. adults: a cross-sectional study.

The relationship between exposure to organophosphate esters (OPEs) and the risk of developing overactive bladder (OAB) is uncertain. The purpose of this study is to examine the potential link between urinary metabolites of organophosphate esters and OAB. Data from the National Health and Nutrition Examination Survey (NHANES) database of the 2011-2016 cycles were utilized. Four urinary metabolites of organophosphate esters: diphenyl phosphate (DPHP), bis (1,3-dichloro-2-propyl) phosphate (BDCPP), bis (2-chloroethyl) phosphate (BCEP), and dibutyl phosphate (DBUP) were included in the study. Multivariate logistic regression and restricted cubic spline (RCS) were used to evaluate the relationship between urinary OPEs metabolites and OAB. Interaction analysis was conducted on subgroups to confirm the findings. A total of 3,443 United States (US) adults aged 20 years or older were included in the study, of whom 597 participants were considered to have OAB. After adjusting for potential confounding factors, we found a positive association between DPHP and the risk of overactive bladder. The risk of overactive bladder increased with increasing DPHP concentrations compared with quartile 1 (quartile 2, OR = 1.19, 95% CI, 0.82-1.73, P = 0.34; quartile 3, OR = 1.67, 95% CI, 1.10-2.53, P = 0.02; Q4, OR = 1.75, 95% CI, 1.26-2.43, P = 0.002). However, after dividing the participants by gender, only the female group retained consistent results. Additionally, restricted cubic spline analysis revealed a nonlinear dose-response correlation between DPHP and OAB in female participants. In the subgroup analysis based on age, race, body mass index (BMI), recreational activity, smoking status, drinking status, hypertension, diabetes, and stroke, the interaction analysis revealed that the findings were uniform. Our findings indicate that exposure to DPHP could elevate the risk of OAB in US adult females. Further experimental studies are needed to explore the underlying mechanism in the future.

Reproductive hormones, organophosphate esters and semen quality: Exploring associations and mediation effects among men from an infertility clinic

Accumulating evidence indicates that organophosphate esters (OPEs) exposure may affect semen quality. As a crucial factor in male reproduction, reproductive hormones might be linked organophosphate esters (OPEs) exposure and semen quality. This study aimed to explore the mediating role of reproductive hormones on the association between OPEs exposure and semen quality. Five serum reproductive hormones, semen quality, and 16 urinary OPE metabolites were measured among 491 reproductive-aged men from a reproductive center. The associations of urinary OPE metabolites with reproductive hormones and semen quality were assessed using multivariable linear regression models, and the mediating role of reproductive hormones was evaluated by mediation analyses. We found that follicle stimulating hormone (FSH) was positively associated with diphenyl phosphate (DPHP) that in turn was negatively associated with sperm total count. In addition, inverse associations were exhibited between serum FSH and sperm concentration, sperm total count, total motility, and progressive motility (all Ptrend <0.05). Mediation analysis further showed that FSH mediated 13.7% of the inverse association of DPHP and sperm total count. Although further investigations are required, our results suggest that FSH was an intermediate mechanism in the associations between OPEs exposure and impaired semen quality.

Determinants of organophosphate esters exposure in pregnant women from East China

Organophosphate esters (OPEs) have been broadly used in various industrial and consumer products, resulting in global distribution and human exposure. Gestational exposure to OPEs may adversely affect the health of both pregnant women and their offspring. To better understand OPE exposure in pregnant women, our study determined eight urinary metabolites of major OPEs in pregnant women (n = 733) recruited at 12–16 weeks of gestation from Shanghai, China, and explored the determinants of OPE exposure among various sociodemographic characteristics, lifestyles, and dietary factors. Urinary metabolites of OPEs, including bis (1,3-dichloro-2-propyl) phosphate (BDCPP), bis (2-chloroethyl) phosphate (BCEP), bis (1-chloro-2-propyl) phosphate (BCIPP), dicresyl phosphate (DCP), diphenyl phosphate (DPP), dibutyl phosphate (DBP), bis (2-ethylhexyl) phosphate (BEHP), and bis (2-butoxyethyl) phosphate (BBOEP), exhibited a detection rate ranging from 69.30% to 99.32%. Multivariate linear regression models indicated that pregnant women who were multiparous, had a higher family income per capita, worked in white-collar jobs, and took nutritional supplements such as milk powder and fish oil tended to have higher urinary OPE metabolite concentrations. Besides, independent of sociodemographic characteristics and lifestyle factors, consumption of more aquatic products, soy products, pork, and puffed food, as well as drinking of purified tap water versus tap water, were associated with increased urinary OPEs metabolite concentrations. Our study demonstrated that OPE exposure was ubiquitous in pregnant women from Shanghai, and provided new insights into the potential factors influencing OPE exposure during pregnancy.

Patterns of urinary organophosphate ester metabolite trajectories in children: the HOME Study.

Organophosphate esters (OPEs) have replaced flame retardant polybrominated diphenyl ethers as flame retardants in consumer products, but few longitudinal studies have characterized childhood OPE exposure. We aimed to examine the exposure pattern of urinary OPE metabolites in children. We quantified three urinary OPE metabolites five times in children (1, 2, 3, 5, 8 years) from 312 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio, USA. We examined the associations of average maternal OPE metabolite concentrations with OPE metabolite concentrations in childhood, characterized childhood OPE trajectories with latent class growth analysis (LCGA), and examined factors related to trajectory membership. Bis(2-chloroethyl) phosphate (BCEP) had the lowest median concentrations over time (0.66-0.97 mg/L) while the median concentrations of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) increased with age (1.44-3.80 mg/L). The median concentrations of diphenyl phosphate (DPHP) fluctuated between 1.96 and 2.69 mg/L. Intraclass correlation coefficients for urinary metabolites measured at five time points indicated high variability within individuals (0.13-0.24). Average maternal urinary BCEP and BDCIPP were associated with concentrations in early childhood. Maternal education, the birth year of the child, and having a carpet in the main activity room were associated with BCEP and BDCIPP trajectory while none of the factors were associated with DPHP trajectory. The trajectory analysis showed different patterns of urinary OPE metabolite concentrations, suggesting the need to collect multiple samples to adequately reflect OPE exposure. In this well-established cohort, we evaluated the patterns of urinary OPE metabolites in children ages 1-8 years. The number of repeated measures over childhood has not been achieved in prior studies. Our results suggested the high variability of urinary OPE metabolites within individuals. Maternal metabolite concentrations during pregnancy were related to child concentrations at ages 1-3 years. BCEP, BDCIPP, and DPHP demonstrated different trajectories in children, which suggests that multiple samples may be required to capture OPE exposure patterns in childhood.

Prenatal exposures to organophosphate ester metabolite mixtures and children’s neurobehavioral outcomes in the MADRES pregnancy cohort

BackgroundEvidence suggests organophosphate esters (OPEs) are neurotoxic; however, the epidemiological literature remains scarce. We investigated whether prenatal exposures to OPEs were associated with child neurobehavior in the MADRES cohort.MethodsWe measured nine OPE metabolites in 204 maternal urine samples (gestational age at collection: 31.4 ± 1.8 weeks). Neurobehavior problems were assessed among 36-month-old children using the Child Behavior Checklist’s (CBCL) three composite scales [internalizing, externalizing, and total problems]. We examined associations between tertiles of prenatal OPE metabolites (> 50% detection) and detect/non-detect categories (< 50% detection) and CBCL composite scales using linear regression and generalized additive models. We also examined mixtures for widely detected OPEs (n = 5) using Bayesian kernel machine regression.ResultsMaternal participants with detectable versus non-detectable levels of bis(2-methylphenyl) phosphate (BMPP) had children with 42% (95% CI: 4%, 96%) higher externalizing, 45% (-2%, 114%) higher internalizing, and 35% (3%, 78%) higher total problems. Participants in the second versus first tertile of bis(butoxethyl) phosphate (BBOEP) had children with 43% (-1%, 109%) higher externalizing scores. Bis(1-chloro-2-propyl) phosphate (BCIPP) and child sex had a statistically significant interaction in internalizing (p = 0.02) and total problems (p = 0.03) models, with 120% (23%, 295%) and 57% (6%, 134%) higher scores in the third versus first BCIPP tertile among males. Among females, detectable vs non-detectable levels of prenatal BMPP were associated with 69% higher externalizing scores (5%, 170%) while the third versus first tertile of prenatal BBOEP was associated with 45% lower total problems (-68%, -6%). Although the metabolite mixture and each CBCL outcome had null associations, we observed marginal associations between di-n-butyl phosphate and di-isobutyl phosphate (DNBP + DIBP) and higher internalizing scores (0.15; 95% CrI: -0.02, 0.32), holding other metabolites at their median.ConclusionsOur results generally suggest adverse and sex-specific effects of prenatal exposure to previously understudied OPEs on neurobehavioral outcomes in 36-month children, providing evidence of potential OPE neurotoxicity.

Nontarget Identification of Novel Organophosphorus Flame Retardants and Plasticizers in Rainfall Runoffs and Agricultural Soils around a Plastic Recycling Industrial Park.

Plastic recycling and reprocessing activities may release organophosphate ester (OPE) flame retardants and plasticizers into the surrounding environment. However, the relevant contamination profiles and impacts remain not well studied. This study investigated the occurrence of 28 OPEs and their metabolites (mOPEs) in rainfall runoffs and agricultural soils around one of the largest plastic recycling industrial parks in North China and identified novel organophosphorus compounds (NOPs) using high-resolution mass spectrometry-based nontarget analysis. Twenty and twenty-seven OPEs were detected in runoff water and soil samples, with total concentrations of 86.0-2491 ng/L and 2.53-199 ng/g dw, respectively. Thirteen NOPs were identified, of which eight were reported in the environment for the first time, including a chlorine-containing OPE, an organophosphorus heterocycle, a phosphite, three novel OPE metabolites, and two oligomers. Triphenylphosphine oxide and diphenylphosphinic acid occurred ubiquitously in runoffs and soils, with concentrations up to 390 ng/L and 40.2 ng/g dw, respectively. The downwind areas of the industrial park showed elevated levels of OPEs and NOPs. The contribution of hydroxylated mOPEs was higher in soils than in runoffs. These findings suggest that plastic recycling and reprocessing activities are significant sources of OPEs and NOPs and that biotransformation may further increase the ecological and human exposure risk.

Urinary concentrations of organophosphate esters and associated health outcomes in Korean firefighters

Although firefighters are at an increased risk of occupational exposure to chemicals, such as flame retardants, research on the exposure of Korean firefighters to organophosphate esters (OPEs)—a group of emerging flame retardants—remains limited. Therefore, in the present study, OPE metabolite concentrations in the urine samples of 149 former and current Korean firefighters were measured. Based on the data obtained, the estimated daily intakes (EDIs) of OPEs were calculated. Subsequently, the association between the urinary concentrations of OPE metabolites and the potential determinants of OPE exposure and health outcomes (e.g., obesity and serum lipids) was investigated. We found that bis(1-chloro-2-propyl) phosphate (BCIPP) and bis(2-chloroethyl) phosphate (BCEP) were the most prevalent urinary OPE metabolites, with median concentrations of 2.33 and 1.80 ng/mL, respectively; these concentrations were higher than those reported previously in other countries, such as the USA and China. Moreover, their parent compounds—tris(1-chloro-2-propyl) phosphate (TCIPP) and tris(2-chloroethyl) phosphate (TCEP)—exhibited EDIs of 126 and 94.8 ng/kg bw/day, respectively. Unlike the high detection rate of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) in other populations, its detection rate in this study was low (6.7%), suggesting regional differences in the exposure pattern of OPEs among countries. Furthermore, occupational characteristics, such as recent participation in firefighting activity, were identified as determinants of the urinary concentrations of OPE metabolites. Total OPE metabolites were inversely associated with body mass index and positively associated with high-density lipoprotein cholesterol. Overall, our findings demonstrate that Korean firefighters are highly exposed to several occupation-related OPEs. Further prospective studies will help elucidate the potential health implications of occupational exposure to OPEs among firefighters.

Organophosphate esters, airway inflammation, and lung function among U.S. participants: A nationally representative cross-sectional study from NHANES, 2011–2012

BackgroundHuman beings are widespread exposed to organophosphate esters (OPEs), but little is known about their effects on respiratory health. ObjectivesTo investigate the associations of exposure to OPEs with lung function and airway inflammation among U.S. participants from NHANES, 2011–2012. MethodsA total of 1636 participants aged 6–79 years were included. Concentrations of OPE metabolites were measured in urine and lung function was assessed with spirometry. Fractional exhaled nitric oxide (FeNO) and blood eosinophils (B-Eos), two important inflammatory biomarkers, were also measured. Linear regression was performed to examine the relationships of OPEs with FeNO, B-Eos and lung function. Bayesian kernel machine regression (BKMR) was used to evaluate the joint associations between OPEs mixtures and lung function. ResultsThree of seven OPE metabolites had detection frequencies > 80 %, including diphenyl phosphate (DPHP), bis (1,3-dichloro-2-propyl) phosphate (BDCPP), bis-2-chloroethyl phosphate (BCEP). A 10-fold increase in DPHP concentrations were associated with 1.02 mL decreases in FEV1 (β = −0.01, 95 % CIs = −0.02, −0.003) and FVC (β = −0.01, 95 % CIs = −0.02, −0.003), respectively, and the similar, modest decreases were seen for BDCPP. For each 10-fold increase in BCEP concentration, FVC was also reduced by 1.02 mL (β = −0.01, 95 % CIs = −0.02, −0.002). Moreover, the negative associations were only found in non-smokers aged >35 years. The aforementioned associations were confirmed by BKMR, but we cannot definitively identify a constituent driving this association. B-Eos was negatively associated with FEV1 and FEV1/FVC, but not with OPEs. No associations were found of FeNO with OPEs and lung function. ConclusionsExposure to OPEs was associated with modest decrements in lung function, although the observed decrease in FVC and FEV1 is unlikely to be of real clinical relevance for the majority of subjects in this series. Moreover, those associations presented age and smoking status-dependent pattern. Unexpectedly, the adverse effect was not mediated by FeNO/B-Eos.