Urinary Organophosphate Esters Metabolites Research Articles

Determination of 16 organophosphate esters in human blood by high performance liquid chromatography-tandem mass spectrometry combined with liquid-liquid extraction and solid phase extraction

人体体液中有机磷酸酯(OPEs)浓度的测定对于了解人体OPEs的暴露水平以及评估人体健康风险具有重要意义。然而,目前的研究大多数集中于尿液中OPEs代谢物含量的分析测定,将其作为人体OPEs暴露的生物标志物,而对人体血液中OPEs的分析研究较少,仅有的少量研究涉及的OPEs种类有限。该研究在优化前处理过程(固相萃取,SPE)和色谱分离的基础上,建立了人体血液中16种OPEs的超高效液相色谱-串联质谱(UPLC-MS-MS)测定方法。血液样品经过乙腈摇床萃取后,经ENVI-18 SPE小柱净化,然后采用Acquity UPLC BEH C18色谱柱,以甲醇/5 mmol/L的乙酸铵水溶液为流动相进行梯度洗脱对目标物进行分离,最后进行LC-MS/MS测定。质谱分析采用电喷雾正离子模式电离,多重反应监测模式测定,内标法定量。在优化的检测条件下,16种OPEs的检出限为0.0038~0.882 ng/mL。除磷酸三甲酯(TMP)外,其余15种OPEs在3个浓度水平的血液基质加标回收率为53.1%~126%,相对标准偏差为0.15%~12.6%。样品的基质效应检测发现,4种OPEs存在明显的基质抑制,选用合适的同位素内标进行定量,可以部分消除基质影响。该方法样品前处理简单,灵敏度高,适用于人体血液样品中OPEs阻燃剂的测定。15个人体血液样本分析结果表明,OPEs的总浓度范围为1.50~7.99 ng/mL,其中8种OPEs的检出率均高于50%,磷酸三异丁酯(TiBP)、磷酸三(2-氯乙基)酯(TCEP)和磷酸三(1-氯-2-丙基)磷酸酯(TCIPP)为主要的OPEs,表明人体存在较为普遍的OPEs暴露,应该引起关注。

Vitamin status on the association between organophosphate esters (OPEs) exposure and chronic kidney disease

Background/Aim: Organophosphate esters (OPEs) are used in various materials and consumer products as flame retardants and plasticizers. Both experimental and epidemiological studies have suggested adverse effects of OPEs on the kidney function. However, it is unknown whether vitamin plays protective role on the OPE-associated chronic kidney disease. In this study, effect modification of vitamin status on the association between OPE exposure and chronic kidney disease was hypothesized. Data from the US National Health and Nutrition Examination Survey (NHANES) 2013-2014 were employed. Methods: A total of 1515 adults were identified in the US NHANES 2013-2014 without kidney failure and current pregnancy and with relevant measurements, e.g., vitamin status (RBC folate, serum vitamin B12, and vitamin D), estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), and urinary metabolites of OPEs. Linear regression models were constructed to evaluate effect modification of vitamin concentrations in the association of urinary metabolites of OPEs, i.e., bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis(2-chloroethyl) phosphate (BCEP), and dibutyl phosphate (DNBP), with eGFR or ACR. Moreover, the association was evaluated following stratification by vitamin status (low-level: <30th percentile; mid-level: ≥30th and <70th percentile; high-level: ≥ 70th percentile). Results: Significant effect modification of vitamin D was observed. Increase of vitamin D was associated with decreased effect sizes of OPEs exposure on the association with eGFR. Following stratification, associations of OPEs exposure with eGFR were significant only in the low-level vitamin D group while the associations were insignificant, and the effect sizes were decreased in the mid- and high-level groups. However, vitamin D did not show any effect modification on ACR. For folate and vitamin B12, no effect modification was observed. Conclusions: Vitamin D status appears to modify the effects of OPEs exposure on chronic kidney disease in general population. Confirmations in other populations are warranted.

Gestational exposure to organophosphate esters (OPEs) and maternal blood pressure during pregnancy: The HOME Study

Background: After the phase-out of polybrominated diphenyl ethers, exposure to organophosphate esters (OPEs), which are potential endocrine disruptors, is ubiquitous. No study has examined the associations between gestational exposure to OPEs and blood pressure and the risk of pregnancy-induced hypertensive diseases.Methods: We used data from 333 women who had liveborn singletons without congenital abnormalities in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort. We quantified maternal urinary OPE metabolites at 16 weeks of gestation. Outcomes included the highest maternal blood pressure measurement at ≥20 weeks of gestation and pregnancy-induced hypertensive diseases (gestational hypertension, preeclampsia, and eclampsia) from medical chart review. We used linear regression and modified Poisson regression with covariate adjustment to estimate the associations of exposure with blood pressure and the risk of pregnancy-induced hypertensive diseases, respectively.Results: Diphenyl phosphate (DPHP) had the highest geometric mean urinary concentrations (1.65 µg/g creatinine), followed by bis(1,3-dichloro-2-propyl) phosphate (BDCIPP; 0.76 µg/g creatinine), bis(2-chloroethyl) phosphate (BCEP; 0.70 µg/g creatinine), and dibutyl phosphate (DBUP; 0.25 µg/g creatinine). There were 29 (8.7%) women diagnosed with pregnancy-induced hypertensive diseases. Average systolic and diastolic blood pressure, measured at an average of 31 weeks gestation (range: 20-41), were 117±13 and 72±9 mmHg, respectively. None of the urinary OPE metabolites were significantly associated with the highest maternal blood pressure at ≥20 weeks of gestation, nor were they strongly associated with an increased risk of pregnancy-induced hypertensive diseases. The relative risk (RR; 95% confidence interval) of pregnancy-induced hypertensive diseases by a 10-fold increase in exposure was 1.31 (0.66, 2.59) for DPHP, 1.36 (0.51, 3.67) for BDCIPP, 0.63 (0.16, 2.39) for BCEP and 2.13 (0.78, 5.77) for DBUP.Conclusion: This study suggests no associations between maternal urinary OPE metabolite concentrations and blood pressure or an increased risk of pregnancy-induced hypertensive diseases during pregnancy.

Urinary organophosphate esters metabolites, glucose homeostasis and prediabetes in adolescents

BackgroundEmerging experimental evidence indicates that organophosphate esters (OPEs) can trigger glucose metabolic disorders. However, human evidence, especially in adolescents, is unavailable. ObjectivesWe utilized data from the National Health and Nutrition Examination Survey 2011–2014 to evaluate whether urinary OPEs metabolites were associated with prediabetes and glucose homeostasis. MethodsA total of 349 adolescents (12-19-year old) who provided at least 8 h fasting blood samples, had urinary OPEs metabolites detected were included. Prediabetes was defined according to the levels of fasting plasma glucose (FPG), 2-h post oral plasma glucose (2 h-OGTT) and glycated hemoglobin A1c (HbA1c). The homeostatic model assessment (HOMA-IR) and the Single Point Insulin Sensitivity Estimator (SPISE) were used to assess insulin resistance and sensitivity, respectively. Multiple binary logistic and linear regressions were used to evaluate the associations with prediabetes and indices of glucose homeostasis. The least absolute shrinkage and selection operator (LASSO) regression was used to assess the associations in a multi-pollutant context. ResultsAfter adjusting for covariates, certain urinary OPEs metabolites were associated with prediabetes and indices of glucose homeostasis in all adolescents. Stratified analyses by sex revealed that such associations were largely sex-dependent. In females, the multiple pollutant models showed that bis(1,3–32 dichloro-2-propyl) phosphate (BDCIPP) was positively associated with prediabetes [odds ratio (OR) = 2.51, 95%CI:1.29, 4.89, for one scaled unit increase in exposure] and 2 h-OGTT (β = 0.07, 95%CI:0.01,0.12); bis(2-chloroethyl) phosphate (BCEP) was negatively associated with fasting insulin (β = −0.10, 95%CI: 0.19,-0.01) and HOMA-IR (β = −0.10, 95%CI: 0.19,-0.003); and detectable bis(1-choloro-2-propyl) phosphate (BCIPP) (>LOD vs < LOD) was inversely associated with 2 h-OGTT (β = −0.11, 95%CI: 0.21,-0.02). In males, consistent inverse associations were found for detectable di-n-butyl phosphate (DNBP) with prediabetes, FPG, 2 h-OGTT, fasting insulin and HOMA-IR. ConclusionUrinary OPEs metabolites were associated with prediabetes and indices of glucose homeostasis in adolescents. But such associations varied by sex. Future studies with multiple measurements of OPEs exposure are needed to confirm our findings.

Organophosphate esters in a cohort of pregnant women: Variability and predictors of exposure

Organophosphate esters (OPEs) are a group of chemicals used as flame retardants and plasticizers that replaced polybrominated diphenyl ethers in consumer products such as furniture and electronics. To characterize exposure to OPEs during fetal development, we measured urinary OPE metabolite concentrations in women twice during pregnancy (16 and 26 weeks' gestation) and at delivery (n = 357). We also previously quantified house dust OPE parent compound concentrations at 20 weeks’ gestation (n = 317). Diphenyl phosphate (DPHP) had the highest geometric mean urinary concentrations (1.5–2.3 μg/g creatinine), followed by bis(1,3-dichloro-2-propyl) phosphate (BDCIPP; 0.75–0.99 μg/g creatinine), and bis(2-chloroethyl) phosphate (BCEP; 0.72–0.97 μg/g creatinine), while dibutyl phosphate (DNBP) had the lowest concentrations (0.25–0.28 μg/g creatinine). Urinary OPE metabolites were moderately correlated with each other at 26 weeks (rs: 0.23–0.38, p < 0.001) while the correlations at 16 weeks and delivery were slightly weaker. Intra-class correlations for urinary metabolites measured at three time points were poor (0.16–0.34), indicating high variability within individuals. Dust concentrations of OPE parent compounds were associated with BCEP, BDCIPP, and DPHP concentrations in urine at some but not all time points. In linear mixed models of urinary OPE metabolite concentrations, household size was inversely associated with BCEP concentrations, and being non-white was associated with lower BDCIPP and DPHP concentrations. Urine samples collected in the summer had the highest OPE metabolite concentrations. This study highlights the need to collect multiple urine samples during pregnancy to define exposure patterns and investigate potential periods of susceptibility.

Urinary metabolites of organophosphate esters in women and their relationship with serum lipids: An exploratory analysis

Organophosphate esters (OPEs) are high-production volume chemicals. Use of OPEs has largely increased since the phase-out/ban of polybrominated diphenyl ethers (PBDEs). The ubiquitous occurrence of OPEs, in higher concentrations in abiotic matrices than brominated flame retardants (BFRs), is a concern because several of the OPEs have been linked to adverse health effects. In this study, urinary metabolites of OPEs were measured in a subset of a population-based sample of women of child bearing age recruited in Ontario, and associations between serum lipid levels and urinary concentrations of OPE metabolites were evaluated. Urine samples (n = 120) were extracted using automated solid phase extraction and analysed by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Diphenyl phosphate (DPHP), bis(2-chloropropyl) phosphate (BCIPP) and bis(1,3-dichloro-2 propyl) phosphate (BDCIPP) were detected with frequencies of 100%, 76% and 75% at median concentrations of 13.8 ng/mL, 0.5 ng/mL and 1.8 ng/mL, respectively. Bis(2-chloroethyl) hydrogen phosphate (BCEP) and di-cresyl phosphate (DCP; mixture of 3 isomers) were detected in 52% and 42% of the samples, respectively. Detected at lower frequencies were 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP, 29%), bis-2(butoxyethyl) phosphate (BBOEP, 11%), and desbutyl-tris-(2-butoxy-ethyl) phosphate (desbutyl TBOEP, 9%). Using multiple regression model, a negative statistically significant correlation was observed between BCEP and cholesterol (p = 0.04), as well as BCEP and total lipid (p = 0.04). Whereas BCIPP was positively and significantly correlated with cholesterol (p = 0.003) and LDL (p = 0.001). Additional work to further explore these relationships and to evaluate more recently identified OPE metabolites is warranted.

Organophosphate ester flame retardants and plasticizers in a Chinese population: Significance of hydroxylated metabolites and implication for human exposure

Organophosphate esters (OPEs) are widely used as flame retardants, plasticizers and defoamers and their exposure are likely associated with a number of adverse effects in humans. In this study, tris(chloroethyl) phosphate and thirteen OPE metabolites including six hydroxylated OPEs (HO-OPEs) were analyzed in 46 urine samples, collected from 8 provinces located across different regions in China. 1-Hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) and 2-hydroxyethyl bis(2-butoxyethyl) phosphate (BBOEHEP) were major metabolites of their parent compounds with detection frequencies of 54.3%–89.1%, which were all higher than their corresponding OPE diesters (2.2%–6.5%). The urine-based estimated daily intake (EDI) of OPEs ranged from 0.06 ng/kg·bw for tris(2-butoxyethyl) phosphate (TBOEP) to 273 ng/kg·bw for 2-ethylhexyl phenyl phosphate. Analyzed with concentrations in paired dust samples, dust exposure to OPEs and their diesters may explain 0.28%–23.8% of the urine-based EDI of OPEs and the contribution of dust TBOEP was the highest. Although direct exposure to OPE diesters in dust showed a minor contribution, their intake via food and drinking water may account for a larger portion of urinary OPE metabolites. Overall, the hazard quotients of four OPEs indicated no immediate exposure risk for the investigated Chinese residents but the cumulative and long-term chronic effects involving exposure to other OPEs and OPE diesters are worth further concerns.

Urinary metabolites of organophosphate esters and implications for exposure pathways in adolescents from Eastern China

Ten urinary biomarkers of organophosphate esters (OPEs) from six parent OPEs were analyzed in urine from adolescents students in Eastern China. Bis (1,3-dichloro-2-propyl) phosphate, urinary biomarker of tris (1,3-dichloro-2-propyl) phosphate (TDCIPP), was detected in all urine samples with the highest residual concentration of 6.2 ng/mL (median). Bis (1-chloro-propyl) hydroxyl-2-propyl phosphate, dibutyl phosphate, biomarkers of tris (1-chloro-2-propyl) phosphate (TCIPP), tri-n-butyl phosphate (TNBP), respectively, and tris (2-chloroethyl) phosphate (TCEP), were also frequently detected with median concentrations of 1.5, 2.6 and 0.3 ng/mL, respectively. Results indicate that exposure to OPEs, in particular to TDCIPP, TNBP, TCIPP and TCEP, was highly prevalent for adolescent students. The exposure pathways of OPEs were then evaluated according to the OPE internal body burdens (IBBs). Three pathways were identified as the main pathways for adolescents exposed to OPEs including dermal absorption, oral intake of food and dust and inhalation.

Urinary metabolites of organophosphate esters (OPEs) are associated with chronic kidney disease in the general US population, NHANES 2013–2014

Organophosphate esters (OPEs) have been widely used in building materials and consumer products as flame retardants and plasticizers. In vitro studies have suggested adverse effects of OPEs on the kidney. Despite accumulating evidence indicating widespread exposure to OPEs, their association with renal function in humans has not been evaluated. This study aims to investigate the association between OPEs exposure and chronic kidney disease (CKD) among the general US adult population by employing data from the US National Health and Nutrition Examination Survey (NHANES) 2013–2014. Among 1578 adults who were not currently pregnant, the associations of the urinary OPE metabolites with two CKD-related parameters, i.e., estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR), and CKD were assessed. To account for urine dilution, in addition to conventional creatinine-adjustment, covariate-adjusted creatinine standardization, which controls for potential confounding by kidney function, was employed. Multi-pollutant models were also constructed to verify the associations observed in the models on individual OPE metabolites. The urinary bis(2-chloroethyl) phosphate (BCEP) level was negatively associated with eGFR only with the covariate-adjusted standardization method, but not with the conventional creatinine adjustment. In addition, both bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and di-n-butyl phosphate (DNBP) were positively associated with the ACR, regardless of methods of urine dilution adjustment. These three compounds were also associated with CKD. Following adjusting urine dilution with the covariate-adjusted standardization method, the association became more evident. Moreover, similar results were observed in the secondary analysis with the multi-pollutant models. Among the US general population, several OPEs were identified as potential chemical determinants of CKD. Experimental studies are warranted to understand the potential mechanisms underlying this observation.

Differential exposure to organophosphate flame retardants in mother-child pairs

BackgroundHumans are ubiquitously exposed to flame retardants, including organophosphate esters (OPEs), through direct contact with consumer products or exposure through household dust. Children are at increased risk because of their proximity to dust, hand-to-mouth activity, and the importance of childhood as a critical period in neurodevelopment. ObjectivesTo quantify differences in exposure levels between mothers and children (three to six years of age), we analyzed urinary metabolites of OPEs. We additionally assessed the ability of silicone wristbands (measuring ambient exposure) to predict urinary metabolite concentrations. MethodsWe selected 32 mother and child dyads from an existing cohort. Participants provided baseline urine samples and wore wristbands for one week. After the first week, they returned their wristbands and provided a second urine sample. During the second week, participants wore a second wristband that they returned at the end of week two with a third and final urine sample. ResultsWe found significantly higher levels of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) (p < 0.001) and lower levels of bis(1-chloro-2-isopropyl) 1-hydroxy-2-propyl phosphate (BCIPHIPP) (p < 0.001) in children's urine samples compared to mothers' samples at baseline. We found that triphenylphosphate (TPHP), tris(1,3-dichloroisopropyl) phosphate (TDCIPP), and tris(1-chloro-2-propyl) phosphate (TCIPP) measured in wristbands predicted their respective metabolite levels in urine. ConclusionChildren had higher levels than mothers for two of six flame retardant metabolites measured in urine. Generally, wristband measurements positively predicted internal dose. As little is known about the health effects of OPEs on child development, future research is needed to determine the impact of differential exposure.

Urinary Metabolites of Organophosphate Esters (OPEs) in Electronic Waste Recycling Workers from the Province of Quebec, Canada

Background: Organophosphate esters (OPEs), which are used as flame retardants and plasticizers, have been measured in the air of electronic waste recycling (E-recycling) plants. Numerous studies suggest that exposure to OPEs may result in adverse health effects and constitute a potential health risk for E-recycling workers. However, data on urinary OPE metabolites in occupationally exposed workers is scarce.Objective: To measure urinary OPE metabolites in E-recycling workers and assess their relationship with personal air OPE levels.Methods: Levels of 13 OPE metabolites were measured, at the end of the work shift, in urine samples from 56 workers (four facilities in Quebec, Canada). Air levels of 11 OPEs were measured in 8-hour personal samples with OSHA XAD-2 versatile samplers. The relationship between air OPE levels and urinary metabolite levels was determined using Spearman&amp;#8217;s rank correlation.Results: Nine of the 13 urinary OPE metabolites were detected in more than 50% of samples. The OPE metabolites with the highest median levels were 1-hydroxy-2-propyl bis (1-chloro-2-propyl) phosphate (OH-BIPCPP) (median: 2.2 ng/mL; maximum: 26), diphenyl phosphate (DPhP) (median: 2.1 ng/mL; maximum: 19), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) (median: 1.2 ng/mL; maximum: 7.4), and bis(2-chloroethyl) carboxymethyl phosphate (tris(1,3-dichloro-2-propyl) phosphate (BICECMP) (median: 0.5 ng/mL; maximum: 16). Urinary OPE metabolite levels were not significantly correlated with air OPE levels (p values were above 0.05).Discussion: The median urinary levels of BDCIPP and DPhP were higher than those observed in workers from a Chinese E-recycling site, although the timing of sample collection differed. These findings suggest that workers from E-recycling plants are exposed to OPEs, but that exposure through routes other than inhalation, and possibly non-occupational sources, may be more important contributors to the absorbed dose.

Infants' Exposure to Organophosphate Esters (OPES)

Organophosphate esters (OPEs) are frequently used as flame retardants and plasticizers in consumer products, including those specifically designed for use by infants (e.g. carseats and play mats). Though data suggest nearly everyone is exposed to OPEs, exposure levels among infants and the factors associated with higher levels of exposure are largely unknown. As a part of the ongoing CHildren&amp;#8217;s Immune ResPonse (CHIRP) Study, urine samples were collected from central North Carolina children at 2 and 12 months of age (89 samples from 61 individual children). Using mass spectrometry methods we measured 6 urinary OPE metabolites in samples. Bis(1,3-dichloropropyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP) were detected in 100% of sample and other metabolites were also detected frequently [&amp;gt;80 of samples contained isopropyl-phenyl phenyl phosphate (ip-PPP), bis(1-chloro-2-propyl) 1-hydroxy-2-propyl phosphate (BCIPHIPP), bis(2-chloro-isopropyl) phosphate (BCIPP), and tert butyl-phenyl phenyl phosphate (tb-PPP)]. Median metabolite concentrations were generally substantially higher than those reported for older children or adults. Age was inversely associated with chlorinated metabolites. For example, BCIPHIPP levels were 3.7 times higher at 2 months of age than at 12 months of age (10&amp;#946;&amp;#61;4.7: 95% Confidence Interval: 3.1, 6.2). Breastfeeding was associated with significantly higher BCIPHIPP levels (10&amp;#946;&amp;#61;1.7: 95% CI: 1.2, 2.5) and suggestively higher levels of several other metabolites, indicating that breastmilk may be a source of exposure to OPEs. Demographic characteristics were associated with urinary metabolites (e.g. maternal education and race) as was the season of sample collection. Ownership and use of various baby products was also associated with OPE metabolites, but patterns varied by age and metabolite. Cumulatively, results indicate that infants have higher levels of exposure to OPEs, raising concerns given infants&amp;#8217; sensitivity to environmental insults.

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.

Urinary metabolites of organophosphate esters: Concentrations and age trends in Australian children

There is growing concern around the use of organophosphate esters (OPEs) due to their suspected reproductive toxicity, carcinogenicity, and neurotoxicity. OPEs are used as flame retardants and plasticizers, and due to their extensive application in consumer products, are found globally in the indoor environment. Early life exposure to OPEs is an important risk factor for children's health, but poorly understood. To study age and sex trends of OPE exposures in infants and young children, we collected, pooled, and analysed urine samples from children aged 0–5years from Queensland, Australia for 9 parent OPEs and 11 metabolites. Individual urine samples (n=400) were stratified by age and sex, and combined into 20 pools. Three individual breast milk samples were also analysed to provide a preliminary estimate on the contribution of breast milk to the intake of OPEs. Bis(1-chloroisopropyl) phosphate (BCIPP), 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP), bis(1,3-dichloroisopropyl) phosphate (BDCIPP), dibutyl phosphate (DBP), diphenyl phosphate (DPHP), bis(2-butoxyethyl) phosphate (BBOEP), bis(2-butoxyethyl) 3-hydroxyl-2-butoxyethyl phosphate (3OH-TBOEP), and bis(2-butoxyethyl) hydroxyethyl phosphate (BBOEHEP) were detected in all urine samples, followed by bis(methylphenyl) phosphate (80%), and bis(2-ethylhexyl) phosphate (BEHP, 20%), and bis(2-chloroethyl) phosphate (BCEP, 15%). Concentrations of tris(2-chloroethyl) phosphate (TCEP), BCEP, tris(2-ethylhexyl) phosphate (TEHP), and DBP decreased with age, while bis(methylphenyl) phosphate (BMPP) increased with age. Significantly higher concentrations of DPHP (p=0.039), and significantly lower concentrations of TEHP (p=0.006) were found in female samples compared to males. The estimated daily intakes (EDIs) via breastfeeding, were 4.6, 26 and 76ng/kg/day for TCEP, TBP and TEHP, respectively, and were higher than that via air and dust, suggesting higher exposure through consumption of breast milk.

Determination of Seven Urinary Metabolites of Organophosphate Esters using Liquid Chromatography-Tandem Mass Spectrometry

Abstract A simple method was developed for simultaneous determination of seven urinary metabolites of organophosphate esters (OPs) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Based on different physical and chemical properties of these OP metabolites, their enrichment and clean-up were performed through solid phase extraction to obtain high-efficient solid phase extraction cartridges, and the washing and elution conditions were optimized. At the same time, the kinetic parameters and mass spectrometry parameters were investigated for getting the qualitative and quantitative characteristic ion pairs for analysis of each metabolites. The results showed that the Oasis WAX solid phase extraction cartridge was suitable for sample enrichment and clean-up, and the optimal elution solvents were 2 mL of 5% ammonia in methanol and 2 mL of methanol. The recoveries of six analytes ranged from 60.5 to 104.0%, whereas the recovery of diethyl phosphate ranged from 17.8% to 36.2%. The complete baseline separations of seven analytes were achieved under optimized chromatographic conditions. The limits of detection and limits of quantification of the seven analytes ranged from 0.005 to 0.2 μg L−1 and 0.02 to 0.5 μg L−1, respectively. The intra-day and inter-day precision results (RSD = 15.4%) showed that this method had good stability and reproducibility. This method was subsequently used to determine OP metabolites in 10 urine samples from the general population in Guangzhou city. The concentrations of the seven OP metabolites in urine samples ranged from 0.5 to 6.7 μg L−1.