A fast method for the determination of personal care product chemicals in human urine using dispersive liquid-liquid extraction and ultra high-performance liquid chromatography-tandem mass spectrometry.

RATIONALE: Personal care product chemicals (PCPCs) are the chemicals used in personal care products. Many of them are endocrine disruptors and have potential adverse effects on humans. The concentrations of PCPCs in urine are the main biomarker for assessing human exposure. METHODS: A method was developed for the simultaneous determination of 14 PCPCs in human urine using dispersive liquid-liquid extraction combined with ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). RESULTS: Compared with liquid-liquid extraction, this method had the advantages of time efficiency, sensitivity, and limited organic solvent consumption. It produced good linearity (0.9965-0.9996), limits of detection (2.82-36.36 pg mL-1 ), limits of quantitation (9.39-121.08 pg mL-1 ), matrix effect (-0.90%-2.55%), intra-day precision (relative standard deviations [RSDs] <15%), and inter-day precision (RSDs <19.9%). The method had satisfactory relative recovery at three concentration levels. CONCLUSIONS: A rapid method was developed for the simultaneous quantification of 14 PCPCs in human urine. The practicability of the method was verified with 21 urine from university students. It is expected that this method will provide a powerful reference for the assessment of exposure to PCPCs in large populations.

Urinary Metabolites of Polycyclic Aromatic Hydrocarbons of Rural Population in Northwestern China: Oxidative Stress and Health Risk Assessment.

Polycyclic aromatic hydrocarbon (PAH) exposure is suspected to be linked to oxidative damage. Herein, ten PAH human exposure biomarkers [hydroxylated PAH metabolites (OH-PAHs)] and five oxidative stress biomarkers (OSBs) were detected in urine samples collected from participants living in a rural area (n = 181) in Northwestern China. The median molar concentration of ΣOH-PAHs in urine was 47.0 pmol mL-1. The 2-hydroxynaphthalene (2-OHNap; median: 2.21 ng mL-1) was the dominant OH-PAH. The risk assessment of PAH exposure found that hazard index (HI) values were <1, indicating that the PAH exposure of rural people in Jingyuan would not generate significant cumulative risks. Smokers (median: 0.033) obtained higher HI values than nonsmokers (median: 0.015, p < 0.01), suggesting that smokers face a higher health risk from PAH exposure than nonsmokers. Pearson correlation and multivariate linear regression analysis revealed that ΣOH-PAH concentrations were significant factors in increasing the oxidative damage to deoxyribonucleic acid (DNA) (8-hydroxy-2'-deoxyguanosine, 8-OHdG), ribonucleic acid (RNA) (8-oxo-7,8-dihydroguanine, 8-oxoGua), and protein (o, o'-dityrosine, diY) (p < 0.05). Among all PAH metabolites, only 1-hydroxypyrene (1-OHPyr) could positively affect the expression of all five OSBs (p < 0.05), suggesting that urinary 1-OHPyr might be a reliable biomarker for PAH exposure and a useful indicator for assessing the impacts of PAH exposure on oxidative stress. This study is focused on the relation between PAH exposure and oxidative damage and lays a foundation for the study of the health effect mechanism of PAHs.

Derivatization of N-Acyl Glycines by 3-Nitrophenylhydrazine for Targeted Metabolomics Analysis and Their Application to the Study of Diabetes Progression in Mice.

N-Acyl glycines (NAGlys) are an important class of metabolites in the detoxification system of the human body. They have been used in the diagnosis of several metabolic diseases. Liquid chromatography-mass spectrometry (LC-MS) is the most frequently used NAGlys detection platform. Here, we describe a simple and sensitive method of NAGlys detection by LC-MS in plasma and urine samples. This approach is based on the use of a derivatization reagent, 3-nitrophenylhydrazine. The reaction is quick in aqueous solution, and no quenching step is needed. To expand the coverage of NAGlys when standards are not available, NAGlys were first identified based on high-resolution LC-MS. Quantification was subsequently carried out on triple quadrupole LC-MS. This approach allowed a much broader measurement of NAGlys (41 NAGlys in total), especially when authentic standards are unavailable. Comprehensive analysis of NAGlys with this new method was applied in plasma and urine samples of db/db diabetic and non-diabetic db/m+ control mice. The majority of detected NAGlys were altered with high differentiation ability in plasma and urine samples from diabetic and non-diabetic mice. These identified NAGlys hold the potential to be diagnostic biomarkers for type II diabetes and diabetic complications.

HE-YOLOv5s: Efficient Road Defect Detection Network.

In recent years, the number of traffic accidents caused by road defects has increased dramatically all over the world, and the repair and prevention of road defects is an urgent task. Researchers in different countries have proposed many models to deal with this task, but most of them are either highly accurate and slow in detection, or the accuracy is low and the detection speed is high. The accuracy and speed have achieved good results, but the generalization of the model to other datasets is poor. Given this, this paper takes YOLOv5s as a benchmark model and proposes an optimization model to solve the problem of road defect detection. First, we significantly reduce the parameters of the model by pruning the model and removing unimportant modules, propose an improved Spatial Pyramid Pooling-Fast (SPPF) module to improve the feature signature fusion ability, and finally add an attention module to focus on the key information. The activation function, sampling method, and other strategies were also replaced in this study. The test results on the Global Road Damage Detection Challenge (GRDDC) dataset show that the FPS of our proposed model is not only faster than the baseline model but also improves the MAP by 2.08%, and the size of this model is also reduced by 6.07 M.

Fabrication of Chitosan-Loaded Multifunctional Wool Fabric for Reactive Dye Digital Inkjet Printing by Schiff Base Reaction.

Improving the development of high-value multifunctional wool fabrics was essential to satisfy diverse needs. Considering the various characteristics of chitosan macromolecules, herein, a padding-cross-linking process was adopted and then multifunctional wool fabrics with outstanding printing effects, shrink resistance, and antibacterial properties were fabricated. The test results showed that chitosan macromolecules loaded successfully on the wool fiber surface by Schiff base reaction. Wool fabrics changed from hydrophobic to hydrophilic due to the existence of chitosan macromolecules. The color strength (K/S value) of the reactive dye inkjet-printed wool fabric was greatly increased from 20.48 to 26.6. The area shrinkage of final samples was 2.53%, which was exceedingly lower than that of the original wool (10.96%). Moreover, the chitosan macromolecules with reactive amino groups endowed wool fabrics with certain antibacterial properties against E. coli and S. aureus. Generally, this study provided guidance for manufacturing multifunctional digital inkjet-printed wool products in mass production.

Occupational exposure to organophosphate esters in e-waste dismantling workers: Risk assessment and influencing factors screening.

Organophosphate esters (OPEs) are increasingly added in electronic products as alternative flame retardants, which may result in high occupational exposure of electronic waste recycling employees. This study investigated occupational exposure to OPEs in an e-waste recycling site in northern China, with intent to explore the impacts of occupational exposure and dismantling manipulation mode. Human urine samples from three sites with different distances from the core dismantling area, including employees from family workshops and plants with centralized management and residents from nearby areas, were collected and analyzed for OPEs' metabolites (mOPEs). The urinary ∑mOPEs' median concentrations (0.910 ng/mL) of all employees were significantly higher than those of residents in Ziya Town (0.526 ng/mL) and Jinghai downtown (0.600 ng/mL), suggesting the risk of occupational OPEs' exposure associated with e-waste dismantling. However, the spatial variation was insignificant for residents with different distances from the e-waste recycling site. Besides, OPEs' exposure levels were significantly affected by manipulation modes and the urinary ∑mOPEs' median concentrations in the employees of family workshops (1.05 ng/mL) were significantly higher than those in plants with centralized management (0.667 ng/mL). The result suggests that mechanical dismantling and active ventilating measures can reduce the OPEs' occupational exposure risk. Moreover, ∑mOPEs were higher in volunteers with age above 50 years old and in the underweight subgroup. Finally, different categories of mOPEs in human urine showed associations with corresponding OPEs in dust samples in the same area.

Spatial distribution and ecological risks of polychlorinated biphenyls in a river basin affected by traditional and emerging electronic waste recycling in South China.

With development of e-waste related legislation in China, formal recycling activities are designated in some areas while informal ones are illegally transferred to emerging areas to avoid supervision. However, the resulting environmental impact and ecological risks are not clear. Here, we investigated the discharge of polychlorinated biphenyls (PCBs) to soil and aquatic environments by e-waste recycling activities in the Lian River Basin, China. The study area included a designated industrial park in the traditional e-waste recycling area (Guiyu, known as the world's largest e-waste center), several emerging informal recycling zones, and their surrounding areas and coastal area. A total of 27 PCBs were analyzed, and the highest concentration was found in an emerging site for soil (354 ng g-1) and in a traditional site for sediment (1350 ng g--1) respectively. The pollution levels were significantly higher in both the traditional and emerging recycling areas than in their respective upstream countryside areas (p = 0.0356 and 0.0179, respectively). Source analysis revealed that the traditional and emerging areas had similar PCB sources mainly associated with three PCB technical mixtures manufactured in Japan (KC600) and the USA (Aroclor 1260 and Aroclor 1262). The PCB pollution in their downstream areas including the coastal area was evidently affected by the formal and informal recycling activities through river runoff. The ecological risk assessments showed that PCBs in soils and sediments in the Lian River Basin could cause adverse ecotoxicological consequences to humans and aquatic organisms.

The association of serum phthalate metabolites with biomarkers of ovarian reserve in women of childbearing age.

Phthalates (PAEs) are widely used plasticizers drawing increasing concern due to reproductive toxicity. However, studies on serum PAEs metabolites (mPAEs) and their associations with human ovarian function remain very scarce. In this study, from April 2019 to August 2020, a total of 297 women of childbearing age were recruited in Tianjin, China. Eleven mPAEs were analyzed in serum samples and eight mPAEs were detected at frequencies > 65% with median concentrations of 0.43-15.3 ng/mL. In multinomial logistic analysis, an increase in serum mono (2-isobutyl) phthalate (miBP) was associated with decline in antral follicle count (AFC) (OR=1.26, 95% CI: 0.99, 1.61) and 5-mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP) was significantly associated with AFC increase (OR=1.43, 95% CI: 1.06, 1.92), which were aligned with the associations found between mPAEs and AMH through generalized linear regression. In multiple linear regression models, per 10% increase in serum mono (2-ethylhexyl) phthalate (mEHP), mono (2-ethyl-5-oxohexyl) phthalate (mEOHP) (oxo-mEHP), and principal component 1 featured for high concentrations of mono-n-butyl phthalate (mBP), miBP and mEHP were associated with 0.15 (95% CI: -0.29, -0.02), 0.01 (95% CI: -0.01, 0.00) and 0.01 (95% CI: -0.02, 0.00) ln-unit decrease in estradiol (E2) levels, respectively, while mono-[(2-carboxymethyl) hexyl] phthalate (mCMHP) (carboxymethyl-mEHP) was positively associated with 0.05 ln-unit increase of E2 (95% CI: 0.02, 0.08). The observed negative associations between mPAEs and the Anti-Müllerian hormone (AMH) also aligned with the change in AFC. Generalized linear regression also revealed nonlinear associations between mono-ethyl phthalate (mEP), mCMHP and follicle-stimulating hormone (FSH). Overall, serum mEHP and its metabolites were negatively associated with E2. miBP was negatively associated with AFC. The nonlinear associations between mPAEs and FSH, and AMH need further study.

Characterization and Determination of 13C-Labeled Nonessential Amino Acids in a 13C5-Glutamine Isotope Tracer Experiment with a Mass Spectrometry Strategy Combining Parallel Reaction Monitoring and Multiple Reaction Monitoring.

Isotopic tracer, a powerful technique for metabolic pathway analysis, is currently widely applied in metabolic flux analysis. However, the qualitative and quantitative analyses of 13C-labeled metabolites pose great challenges, especially in complex biological sample matrices. Here, we present an integrated method for the qualitative and quantitative analyses of various isotopologues and isotopomers of 13C-labeled nonessential amino acids (NEAAs) in HepG2 cells incubated with 13C5-glutamine (Gln) based on ultra-high-performance liquid chromatography (UHPLC) coupled with tandem mass spectrometry (MS). First, accurate mass-to-charge (m/z) values of protonated isotopologues and elution time of standards were simultaneously analyzed to characterize 13C-labeled NEAAs by high-resolution Orbitrap MS in the parallel reaction monitoring (PRM) mode. Second, isotopologues and isotopomers of 13C-labeled NEAAs were investigated in HepG2 cells incubated with 13C5-Gln at different time points. Ultimately, a total of 66 multiple reaction monitoring (MRM) transitions were performed by UHPLC coupled with triple quadrupole MS. Among them, 29 MRM transitions were monitored for pure metabolites (unambiguously identified). The other 37 MRM transitions were monitored for mixtures with exactly identical MRM transitions and retention time. The application of targeted profiling of 13C-labeled NEAAs in the dynamic 13C-labeling experiment indicated that the concentration-time profiles of NEAAs were different from each other. The concentrations of most 13C-labeled Gln, Glu, Pro, and Asp altered after 13C5-Gln incubation, indicating that Gln plays a fundamental role in the biosynthesis of Glu, Pro, and Asp. The proposed PRM-MRM combination mode LC-MS approach is expected to provide valuable insights into analyses of isotope-labeled metabolites in isotope tracer experiments.

Minimally invasive strategy for type I choledochal cyst in adult: combination of laparoscopy and choledochoscopy.

BACKGROUND: Choledochal cyst (CC)is a rare disease entity, more commonly occurring in Asian populations. In case of no contraindication, CC is resected to avoid future malignancies and future complications. OBJECTIVE: To determine the optimal technique for treatment of patients with type I choledochal cyst by comparisons of indicators, including the duration of surgery, loss of blood, rates of complication, duration of hospitalization, and outcomes of long-term follow-up. METHODS: From January 2009 to September 2017, a combination of laparoscopy and choledochoscopy surgery was implemented for type I choledochal cyst in adult. Patients' demographics data and treatment outcomes were collected prospectively during the follow-up. RESULTS: Fifty-eight patients with type I choledochal cyst were managed using this strategy. The combination of laparoscopic and intraoperative choledochoscopy was successfully performed in all patients without conversion or morbidity. When compared with a historical cohort of 71 patients who underwent a surgery for CC, this group of patients had significantly shorter duration of hospitalization (9.0 ± 6.5 days vs. 13.0 ± 8.0 days, P < 0.05). We also observed a lower blood loss (128.8 ± 60.2 mL vs. 178.1 ± 58.2 mL, P < 0.05), although the duration of the surgery (320.0 ± 50.0 min vs. 190.0 ± 24.5 min, P < 0.05) was longer. However, no significant difference was found in the rate of postoperative bleeding complication (3.45% vs. 4.23%, P = 0.82) and bile leakage complication (6.90% vs. 4.23%, P = 0.51). The two groups had similar rates of anastomotic stenosis (0.96% vs. 0.61%%, P = 0.47), jaundice (0.58% vs. 0.61%, P = 0.95), cholangitis (0.38% vs. 0.30%, P = 0.81), and reoperation (0.38% vs. 0.15%, P = 0.43). CONCLUSION: The type I choledochal cyst in adult can be effectively managed by laparoscopic surgery combined with inoperative choledochoscopy, which is feasible and minimally invasive. With the development of laparoscopic techniques and instruments, laparoscopic surgery may become the first-choice treatment for type I choledochal cyst treatment.

Paraben Exposure Related To Purine Metabolism and Other Pathways Revealed by Mass Spectrometry-Based Metabolomics.

Parabens are widely used as common preservatives in the pharmaceutical and cosmetic industries. Exposure to parabens has been found to be associated with metabolic alterations of human and an increased risk of metabolic disease, such as diabetes. However, limited information is available about metabolic pathways related to paraben exposure. In this study, three parabens were determined in the urine samples of 88 pregnant women by using ultrahigh-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QqQ MS). The samples were divided into different groups based on tertile distribution of urinary paraben concentrations. Metabolic profiling of the 88 urine samples was performed by using UHPLC coupled with Orbitrap high-resolution MS. Differential metabolites were screened by comparing the profiles of urine samples from different paraben-exposure groups. The identified metabolites included purines, acylcarnitines, etc., revealing that metabolic pathways such as purine metabolism, fatty acid ß-oxidation, and other pathways were disturbed by parabens. Eighteen and three metabolites were correlated (Spearman correlation analysis, p < 0.05) with the exposure levels of methyparaben and propylparaben, respectively. This is the first MS-based nontargeted metabolomics study on pregnant women with paraben exposure. The findings reveal the potential health risk of exposure to parabens and might help one to understand the link between paraben exposure and some metabolic diseases.

Association between phthalate exposure and blood pressure during pregnancy.

BACKGROUND: Phthalates are endocrine disrupting chemicals (EDCs) that pose a serious hazard to the human health. Many epidemiological studies revealed a relationship between phthalates exposure and blood pressure in general population, while the relationship in pregnant women remains unknown. OBJECTIVES: Aimed to elucidate whether phthalate exposure is associated with blood pressure among pregnant women. METHODS: This study included 636 participants from Wuhan, China. Urine samples were conducted repeatedly in three trimesters, and 9 phthalates were measured in these samples. After each urine was sampled, all the participants completed blood pressure measurements. Associations between repeated measurements of phthalate concentration and blood pressure were evaluated by using generalized estimating equations. Stratified analysis by fetus gender was conducted. RESULTS: Among the pregnant women with male fetuses, mono-i-butyl phthalate (MiBP) exposed in the 1st trimester was associated with the increased diastolic blood pressure (DBP) measured in the 2nd trimester, while the environmental risk score (ERS) measured in the 1st and 2nd trimester was positively associated with systolic blood pressure (SBP) and DBP in the 2nd trimester. No significant relationships were observed among all the population or pregnant women with female fetuses. CONCLUSIONS: Exposure to higher levels of MiBP may be related to increased blood pressure during pregnancy in pregnant women with male fetuses.

Large-Scale Longitudinal Metabolomics Study Reveals Different Trimester-Specific Alterations of Metabolites in Relation to Gestational Diabetes Mellitus.

Despite the increasing research attention paid to gestational diabetes mellitus (GDM) due to its high prevalence, limited knowledge is available about its pathogenesis. In this study, 428 serum samples were collected from 107 pregnant women suffering from GDM and 107 matched healthy controls. The nontargeted metabolomics data of maternal serum samples from the first (T1, n = 214) and second trimesters (T2, n = 214) were acquired by using ultrahigh performance liquid chromatography coupled with Orbitrap mass spectrometry (MS). A total of 93 differential metabolites were identified on the basis of the accurate mass and MS/MS fragmentation. After false discovery rate correction, the levels of 31 metabolites in GDM group were significantly altered in the first trimester. The differential metabolites were mainly attributed to purine metabolism, fatty acid ß-oxidation, urea cycle, and tricarboxylic acid cycle pathways. The fold changes across pregnancy (T2/T1) of six amino acids (serine, proline, leucine/isoleucine, glutamic acid, tyrosine, and ornithine), a lysophosphatidylcholine (LysoPC(20:4)), and uric acid in GDM group were significantly different from those in the control groups, suggesting that these 8 metabolites might have contributed to the occurrence and progression of GDM. The findings revealed that the amino acid metabolism, lipid metabolism, and other pathways might be disturbed prior to GDM onset and during the period from the first to the second trimester of pregnancy.

Simultaneous determination of amino acids, purines and derivatives in serum by ultrahigh-performance liquid chromatography/tandem mass spectrometry.

RATIONALE: Amino acids, purines and derivatives play a key role in physiological and pathological processes, such as the development of gestational diabetes mellitus. However, little literature has reported the simultaneous quantification of amino acids and purines. Therefore, a reliable and robust method for the determination of amino acids and purines is necessary. METHODS: A rapid and simple method based on ultrahigh-performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS) was developed to determine the concentrations of twenty amino acids or derivatives and three purines or derivatives in serum. RESULTS: The method was validated for linearity of calibration curve, limit of detection, limit of quantification, inter-day and intra-day precision, recovery, stability and matrix effect. The correlation coefficients of calibration curves were higher than 0.993 except for isoleucine. The recoveries ranged from 78.4% to 128.0% for three different concentrations of the spiked analytes. The matrix effect value ranged from -7.3% to 9.2%. CONCLUSIONS: A rapid and simple UHPLC/MS/MS method for the simultaneous measurement of amino acids, purines and derivatives in serum samples was developed. The method was successfully applied to determine and compare the concentrations of analytes between gestational diabetes mellitus samples and controls.

Integration of Metabolomics and Lipidomics Reveals Metabolic Mechanisms of Triclosan-Induced Toxicity in Human Hepatocytes.

Triclosan (TCS), an extensively used antimicrobial agent, has raised considerable concern due to its hepatocarcinogenic potential. However, previous hepatotoxicity studies primarily focused on the activation of specific intracellular receptors, the underlying mechanisms still warrant further investigation at the metabolic level. Herein, we applied metabolomics in combination with lipidomics to unveil TCS-related metabolic responses in human normal and cancerous hepatocytes. Endogenous and exogenous metabolites were analyzed for the identification of metabolic biomarkers and biotransformation products. In L02 normal cells, TCS exposure induced the up-regulation of purine metabolism and amino acid metabolism, caused lipid accumulation, and disturbed energy metabolism. These metabolic disorders in turn enhanced the overproduction of reactive oxygen species (ROS), leading to the alteration of antioxidant enzyme activities, down-regulation of endogenous antioxidants, and peroxidation of lipids. TCS-induced oxidative stress is thus considered to be one crucial factor for hepatotoxicity. However, in HepG2 cancer cells, TCS underwent fast detoxification through phase II metabolism, accompanied by the enhancement of energy metabolism and elevation of antioxidant defense system, which contributed to the potential effects of TCS on human hepatocellular carcinoma development. These different responses of metabolism between normal and cancerous hepatocytes provide novel and robust perspectives for revealing the mechanisms of TCS-triggered hepatotoxicity.

Exposure Assessment of Bisphenols in Chinese Women during Pregnancy: A Longitudinal Study.

Bisphenol S (BPS) and bisphenol F (BPF) are increasingly used in manufacturing consumer products to replace the use of bisphenol A (BPA), but exposure data are limited, particularly among pregnant women. Here, we measured BPA, BPS, and BPF levels in urine samples, collected from 941 pregnant women over three trimesters. We examined the correlations, coexposure patterns, variability, and predictors of bisphenols using Spearman's correlation coefficient, percentile analysis, intraclass correlation coefficient, and linear mixed models, respectively. We assessed health risks using average concentrations of bisphenols over three trimesters. The three bisphenols were detected in more than 50% of samples, among which BPA was the predominant one. Cashiers, office workers, teachers, and salespersons had elevated urinary BPS concentrations, while healthcare workers had relatively higher BPA concentrations. About 15 participants had potential health risks induced by exposure to bisphenol mixtures. These findings indicate that exposure to multiple bisphenols at low levels is common over three trimesters. Multiple measurements of urinary BPA and BPS concentrations are needed for more accurate evaluation of the exposure levels during pregnancy, while urinary BPF concentrations during pregnancy are moderately reliable. Occupational exposure should be taken into consideration in future demographic studies.

Mass Spectrometry-Based Metabolomics Reveals Occupational Exposure to Per- and Polyfluoroalkyl Substances Relates to Oxidative Stress, Fatty Acid ß-Oxidation Disorder, and Kidney Injury in a Manufactory in China.

Occupational workers are usually exposed to high levels of per- and polyfluoroalkyl substances (PFASs), placing them under greater health risks compared to the general population. Herein, 40 occupational workers from a factory in China and 52 control subjects from the general population were involved in an investigation on the potential health concerns of occupational exposure to PFASs by mass spectrometry-based metabolomics analysis. The PFAS levels in plasma from both groups were analyzed. Six PFAS congeners (∑6PFASs) were found to be the main components of the 13 detected PFASs, with a geometric mean of 1770 and 22.2 ng mL-1 in occupational workers and the general population, respectively. Metabolic profiles of the plasma samples were acquired using liquid chromatography coupled with orbitrap high-resolution mass spectrometry and gas chromatography-mass spectrometry. The partial least-squares-discriminant analysis model indicated that the plasma metabolic profiles of the two groups could be clearly separated. Differential and correlation analyses were applied to discover potential biomarkers. A total of 14 potential biomarkers were identified, and they were found to be associated with oxidative stress, fatty acid ß-oxidation disorder, and kidney injury. The obtained results indicated that the health effects of occupational exposure to PFASs on workers should not be ignored.

Variations, Determinants, and Coexposure Patterns of Personal Care Product Chemicals among Chinese Pregnant Women: A Longitudinal Study.

Exposure to mixtures of personal care product chemicals (PCPCs) is commonplace among the Chinese population; yet, limited data are available on the variations, determinants, and coexposure patterns of PCPCs, particularly among pregnant women at multiple time points during gestation. Here, we measured concentrations of 11 most common PCPCs (five parabens, five benzophenones, and triclosan) in 2823 urine samples collected from 941 pregnant women over three trimesters. Based on the quantification results, we calculated the intraclass correlation coefficient (ICC) to assess within-person variability of targeted compounds, applied linear mixed mode models to explore associations between urinary concentrations of PCPCs and exposure-related factors, and used percentile analysis to evaluate exposure to specific or multiple chemicals at one or three trimesters. Seven targeted compounds: methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), 4-hydroxybenzophenone (4-OH-BP), 2,4-dihydroxybenzophenone (BP-1), 2-hydroxy-4-methoxybenzophenone (BP-3), and triclosan (TCS) were detected in over 66% of samples. The median urinary concentrations (ng/mL) of MeP, EtP, PrP, 4-OH-BP, BP-1, BP-3, and TCS were 15.44, 0.49, 0.61, 0.16, 0.25, 0.53, and 0.48, respectively. We observed that benzophenones (ICC: 0.46-0.55) and triclosan (ICC: 0.50) were less variable than parabens (ICC: 0.35-0.40). Urinary levels of parabens were related to physical activity frequency; urinary levels of benzophenones were associated with the refurbishment of homes and household income, and urinary levels of triclosan were contingent upon the personal basic information (prepregnancy body mass index and age). Notably, higher levels of benzophenones and triclosan but lower paraben levels were observed in summer than in winter. Both coexposure to high percentiles of multiple pollutants at one trimester and exposure to one pollutant at high-dose through three trimesters were rare in the study population. Our findings suggest that these exposure-related factors should be taken into consideration, and health risks should be assessed on mixtures of pollutants in future epidemiological studies.

Repeated Measurements of Paraben Exposure during Pregnancy in Relation to Fetal and Early Childhood Growth.

Parabens are potential endocrine disruptors with short half-lives in the human body. To date, few epidemiological studies regarding repeated paraben measurements during pregnancy associated with fetal and childhood growth have been conducted. Within a Chinese prenatal cohort, 850 mother-infant pairs from whom a complete set of maternal urine samples were acquired during three trimesters were included, and the levels of five parabens were measured. We assessed the associations of both average and trimester-specific urinary paraben levels with weight and height z-scores at birth, 6 months, 1, and 2 years of age. In all infants, each doubling increase in average ethyl paraben (EtP) was associated with -2.82% (95% CI: -5.11%, -0.53%) decrease in weight z-score at birth, whereas no significant age-specific associations were identified. After stratifying by sex, we further observed age-specific association of average EtP with -3.96% (95% CI: -7.03%, -0.89%) and -3.38% (95% CI: 6.72%, -0.03%) reduction in weight z-scores at 1 and 2 years in males, respectively. Third-trimester EtP was negatively associated with weight z-scores at birth, 1 and 2 years in males. Our results suggested negative associations between prenatal paraben exposure and fetal and childhood growth, and the third trimester may be the window of susceptibility.

Performance of atmospheric pressure gas chromatography-tandem mass spectrometry for the analysis of organochlorine pesticides in human serum.

A novel method of atmospheric pressure gas chromatography-tandem mass spectrometry (APGC-MS/MS) for the analysis of organochlorine pesticides (OCPs) in human serum was developed. Better sensitivity and selectivity were achieved compared to conventional gas chromatography-mass spectrometry (GC-MS) and GC-MS/MS. The limits of detection (LODs) of OCPs ranged from 0.22 to 0.90 pg/mL for the analysis in serum samples. The recoveries and repeatability of the developed method were evaluated from the analysis of spiked serum at three levels (0.05, 0.5, and 5 ng/mL). The recoveries ranged from 84.5 to 118.2%, and the relative standard deviations (RSDs) were less than 20%. The developed APGC-MS/MS method was applied to measure OCPs in pooled human serum from the interlaboratory comparison study. The obtained results of OCPs were within the acceptable ranges. The method has been successfully applied to the analysis of OCPs in human serum samples with the sample volume of up to 100 µL. Graphical abstract.