BackgroundPer- and polyfuoroalkyl substances (PFAS) are categorized as persistent organic pollutants and commonly detected in humans, and their toxicity has attracted widespread attention. However, few studies have reported comparison of PFAS levels and potential factors between women pregnant using assisted reproduction technology (ART) and women pregnant naturally. ObjectiveTo analyze and compare serum concentrations and sociodemographic determinants of PFAS in pregnant women conceiving through ART and conceiving naturally from Shanghai. MethodsBased on the China National Birth Cohort (CNBC) in Shanghai from 2017 to 2019, 333 pregnant women conceiving through ART and 689 pregnant women conceiving naturally were recruited during the same period as study subjects. The concentrations of 32 PFAS were measured in early-pregnancy serum of all pregnant women, and four PFAS with the highest co-exposure levels in both groups were included in the subsequent analysis. Multiple linear regression models were performed to evaluate the associations of sociodemographic factors with serum PFAS concentrations in the two groups respectively. Beta coefficients and 95% confidence intervals (CI) were exponentiated to calculate the ratio of the geometric mean (GM) of PFAS concentrations after each unit change in the independent variable.ResultsPerfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), 6∶2 chlorinated polyfluoroethersulfonic acid (6∶2 Cl-PFESA), and perfluorohexanesulfonic acid (PFHxS) were four major PFAS in serum of pregnant women conceiving through ART and conceiving naturally, and the concentrations of PFOA, PFOS, and 6∶2 Cl-PFESA were higher in pregnant women conceiving through ART than in pregnant women conceiving naturally (P <0.05). The results of multiple linear regression analysis showed that age at pregnancy and household income were associated with serum PFAS levels in both groups. The serum concentrations of PFOS were higher in pregnant women aged ≥35 years old who conceiving through ART (GM ratio=1.26, 95%CI: 1.04, 1.54) and conceiving naturally (GM ratio=1.24, 95%CI: 1.08, 1.42) than pregnant women aged <30 years old respectively. Pregnant women conceiving through ART and conceiving naturally whose household annual income >300000 CNY had lower serum concentrations of PFOA [GM ratio (95%CI): 0.82 (0.72, 0.95) and 0.89 (0.81, 0.97), respectively] and PFHxS [GM ratio (95%CI): 0.66 (0.51, 0.86) and 0.77 (0.66, 0.90), respectively] than those women whose household annual income <200000 CNY. Additionally, pregnant women conceiving naturally with a graduate education or above had lower serum 6∶2 Cl-PFESA concentrations than women with an education below college (GM ratio: 0.81), and multiparous pregnant women conceiving naturally had higher serum concentrations of PFOS, 6∶2 Cl-PFESA, and PFHxS than primiparous pregnant women (GM ratio: 1.14, 1.25, and 1.27 respectively). ConclusionAlthough differences in serum PFAS levels are found between pregnant women conceiving through ART and women conceiving naturally in this study, maternal age and household income are common determinants of PFAS exposure levels in both populations. We find no special sociodemographic factors to affect PFAS concentrations of pregnant women conceiving through ART compared to pregnant women conceiving naturally. Further research is required to explore other potential factors.

BACKGROUND:Previous studies have suggested that prenatal exposure to organophosphate flame retardants (OPFRs) may have adverse effect on early neurodevelopment, but limited data are available in China, and the overall effects of OPFRs mixture are still unclear. OBJECTIVE:This study aimed to investigate the association between prenatal exposure to OPFR metabolites mixture and the neurodevelopment of 1-year-old infants. METHODS:A total of 270 mother-infant pairs were recruited from the Laizhou Wan (Bay) Birth Cohort in China. Ten OPFR metabolites were measured in maternal urine. Neurodevelopment of 1-year-old infants was assessed using the Gesell Developmental Schedules (GDS) and presented by the developmental quotient (DQ) score. Multivariate linear regression and weighted quantile sum (WQS) regression models were conducted to estimate the association of prenatal exposure to seven individual OPFR metabolites and their mixture with infant neurodevelopment. RESULTS:The positive rates of seven OPFR metabolites in the urine of pregnant women were greater than 70% with the median concentration ranged within 0.13-3.53 μg/g creatinine. The multivariate linear regression model showed significant negative associations between bis (1-chloro-2-propyl) phosphate (BCIPP), din-butyl phosphate (DnBP), and total OPFR metabolites exposure and neurodevelopment in all infants. Results from the WQS model consistently revealed that the OPFR metabolites mixture was inversely associated with infant neurodevelopment. Each quartile increased in the seven OPFR metabolites mixture was associated with a 1.59 decrease (95% CI: 2.96, -0.21) in gross motor DQ scores, a 1.41 decrease (95% CI: 2.38, -0.43) in adaptive DQ scores, and a 1.08 decrease (95% CI: 2.15, -0.02) in social DQ scores, among which BCIPP, bis (1, 3-dichloro-2-propyl) phosphate (BDCIPP) and DnBP were the main contributors. CONCLUSION:Prenatal exposure to a mixture of OPFRs was negatively associated with early infant neurodevelopment, particularly in gross motor, adaptive, and social domains.

The combined exposure to environmental pollutants can result in unanticipated adverse effects on human health, and how to compare and assess these effects has always been a matter of great concern for the international community. Currently, several prevalent methods for assessing combined exposure risks in the field of human health risk assessment primarily encompass the hazard index (HI) method, the point of departure index (PODI) method, the margin of exposure (MOE) method, and the relative potency factor (RPF) method. The review summarizes the application of these methods to the cumulative risk assessment of combined exposure to the same class of chemicals with the same toxic mechanism, primarily focusing on pesticides such as organophosphorus pesticides, pyrethroids, carbamates, and neonicotinoids, as well as typical compounds intimately related to human production and life, including organophosphorus flame retardants, per- and poly-fluoroalkyl substances, and bisphenols. Furthermore, progress in the application of physiologically based pharmacokinetics models to human health risk assessment has been introduced, which might provide more options for risk assessment of combined exposure to multiple chemicals, and help to provide insights for further exploration and establishment of more systematic and scientific approaches to human health risk assessment.

Bisphenol A (BPA) and its alternatives bisphenol S (BPS) and bisphenol F (BPF) are identified as endocrine disruptors that have negative impacts on infant growth. Their temporal variations in human milk and potential effects on fetal growth are not well known. In this study, colostrum collecting at four time points between 2006 and 2019 and paired urine in 2019 from Shanghai, China, were analyzed for eight bisphenols. The total concentrations in colostrum in 2019 were up to 3.43 ng/mL, with BPA being dominant, followed by BPS and BPF. BPA levels in colostrum noticeably decreased from 2010 to 2013. Additionally, obvious percentage changes in bisphenols were observed in 2019. The BPA concentrations in paired colostrum and urine were not significantly correlated. High levels of BPA in colostrum were linked to a significant reduction in birth head circumference in 2019 (p = 0.031). BPA and BPS in colostrum might have similar negative effect on fetal growth in 2019, but these effects were generally non-significant. Further studies are needed to testify the potential impact. The hazard indexes for infants in the first week of life were below 1, suggesting no obvious health risks. However, the high contribution from BPA still warrants further attention.

Background: Organophosphate flame retardants (OPFRs) are widely used as flame retardants and plasticizers. Laboratory evidence has suggested that maternal OPFR exposure may adversely affect fetal growth, but the epidemiological data are limited. Objectives: To investigate the association of maternal OPFR exposure with neonatal anthropometric measures.Methods: This study included 354 mother-newborn pairs from the Laizhou Wan Birth Cohort (LWBC), China. Ten OPFR metabolites were measured in maternal urine samples collected before delivery. Neonatal anthropometric data was collected from medical records and standardized into z-scores using the WHO standards (2007), including the weight-for-age (WAZ), length-for-age (LAZ), body mass index-for-age (BMIZ), weight-for-length (WLZ), and head circumference-for-age z-score (HCZ). Multiple linear regression and weighted quantile sum (WQS) regression were used to estimate the associations of individual OPFR metabolites and their mixtures with neonatal anthropometrics, respectively. Stratified analysis by sex was performed.Results: The detection rates of BCEP, DPHP, BCIPP, BDCIPP, BBOEP, DnBP and DiBP were above 60%, with median concentrations ranging from 0.14 to 3.60 & mu;g/g creatinine. Most OPFR metabolites (i.e., BCIPP, BDCIPP, DiBP, DnBP, or BBOEP) were associated with decreased offspring WAZ and HCZ. When using WQS analysis, the OPFR metabolite mixture was inversely associated with the WAZ, BMIZ and HCZ, whereas DnBP had the highest weights. After stratified by gender, the negative associations were more pronounced among males.Conclusions: Maternal OPFR exposure was negatively associated with offspring WAZ, BMIZ, and HCZ, and males seemed to be more vulnerable to the developmental toxicity of certain OPFRs.

[背景]新烟碱类杀虫剂(NEOs)是一种新型合成杀虫剂,其作为传统农药的替代品被广泛应用于全球的害虫防治.近期研究表明人类广泛暴露于该类杀虫剂,但关于儿童的NEOs暴露水平和健康风险评估有限.[目的]探索山东莱州湾5岁儿童尿液样本中4种NEOs的暴露水平,并评估该地区儿童单一和累积暴露于该类杀虫剂的健康风险.[方法]以山东莱州湾出生队列(LWBC)中参与5岁随访的205名儿童为研究对象,采用高效液相色谱-三重四级杆串联质谱的方法检测尿液样本中4种NEOs的暴露水平,包括吡虫啉(IMI)、啶虫脒(ACE)、噻虫胺(CLO)和噻虫嗪(THM).基于检测的NEOs浓度计算其每日估计暴露量(EDI),并采用危害商(HQ,风险阈值为1)法评估NEOs单一暴露的健康风险;利用相对效能因子(RPF)法对4种NEOs的浓度进行IMI标准化校正以计算其累积暴露浓度,再基于HQ法进一步探究累积暴露于4种NEOs的健康风险.[结果]5岁儿童尿液样本中4种NEOs的检出率均在90％以上,其肌酐校正后的中位浓度从高到低依次为:CLO(1.373μg·g-1)＞THM(0.628μg·g-1)＞IMI(0.310μg·g-1)＞ACE(0.073μg·g-1).4 种 NEOs中,IMI 的 EDI 中位数为 0.035 μg·kg-1·d-1,高于 CLO(0.032 μg·kg-1·d-1)、THM(0.012 μg·kg-1·d-1)和ACE(0.002 μg·kg-1·d-1)的EDI中位数.IMI、CLO、THM和ACE的HQ最大值分别为0.168、0.152、0.055和0.022,均远低于风险阈值1.4种NEOs经IMI标准化校正后的累积暴露浓度的中位数为21.241 μg·g-1,其EDI的中位数为2.370 μg·kg-1 d-1,累积暴露于4种NEOs的HQ最大值也仅为0.694,未超过风险阈值1.[结论]山东莱州湾5岁儿童NEOs暴露较为普遍.尽管该地区儿童单一和累积暴露于NEOs未见明显的健康风险,但与国外部分地区相比,其NEOs的暴露水平更高,长期低剂量暴露于该类杀虫剂可能引起的不良健康效应值得广泛关注.

Organophosphate flame retardants (OPFRs) and organophosphate pesticides (OPPs), pertaining to organophosphate esters, are ubiquitous in environment and have been verified to pose noticeable risks to human health. To evaluate human exposures to OPFRs and OPPs, a fast and sensitive approach based on a solid phase extraction (SPE) followed by the ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) detection has been developed for the simultaneous analysis of multiple organophosphorus metabolites in urine. The method allows the identification and quantification of ten metabolites of the most common OPFRs and all six dialkylphosphates (DAPs) of OPPs concerning the population exposure characteristics. The method provided good linearities (R2 = 0.998-0.999), satisfactory method detection limits (MDLs) (0.030-1.129 ng/mL) and only needed a small volume (200 μL) of urine. Recovery rates ranged 73.4-127.1% at three spiking levels (2, 10 and 25 ng/mL urine), with both intra- and inter-day precision less than 14%. The good correlations for DAPs in a cross-validation test with a previous gas chromatography-mass spectrometry (GC-MS) method and a good inter-laboratory agreement for several OPFR metabolites in a standard reference material (SRM 3673) re-enforced the precision and validity of our method. Finally, the established method was successfully applied to analyze 16 organophosphorus metabolites in 35 Chinese children's urine samples. Overall, by validating the method's sensitivity, accuracy, precision, reproducibility, etc., data reliability and robustness were ensured; and the satisfactory pilot application on real urine samples demonstrated feasibility and acceptability of this method for being implemented in large population-based studies.

Persistent halogenated organic pollutants (HOPs) are a class of toxic chemicals, which may have adverse effects on fetuses via transplacental transfer from their mothers. Here, we review reported internal exposure levels of various HOPs (organochlorinated pesticides, polychlorinated biphenyls, polybrominated diphenyl ethers, short- and medium-chain chlorinated paraffins, and per- and poly-fluoroalkyl substances) in placenta, and both maternal and umbilical cord sera. We also present analyses of the transplacental transfer and placental distribution characteristics of each class of compounds, and discuss effects of several factors on the transfer and accumulation efficiencies of HOPs, as well as the main mechanisms of HOPs' transfer across the placental barrier. Reported compound-specific transplacental transfer efficiencies and distribution efficiencies, expressed as umbilical cord:maternal serum and placental:maternal serum concentration ratios (RCM and RPM, respectively), are summarized. Average published RCM values of the HOPs range from 0.24 to 3.08 (lipid-adjusted) and from 0.04 to 3.1 (based on wet weights), and are highest for perfluoroalkylcarboxylates (PFCAs) and tetrabromobisphenol A. Average published RPM values range from 0.14 to 1.02 (lipid-adjusted) and from 0.30 to 1.4 (based on wet weights). The broad RCM and RPM ranges may reflect effects of various factors, inter alia physicochemical properties of HOPs, metabolic capacities of mothers and fetuses, placental maturity, and differential expression of influx/efflux transporters in the placenta. Generally, HOPs' RCM values decline linearly with molecular size, and are curvilinearly related to solubility. Plasma protein binding affinity and the difference between maternal and fetal metabolic capacities may also affect some HOPs' transfer efficiencies. HOPs' molecular size may be influential. Transplacental transport of HOPs likely occurs mostly through passive diffusion, although influx/efflux transporters expressed on maternal and/or fetal sides of the placenta may also facilitate or hinder their transport. Overall, the review highlights clear gaps in our understanding of mechanisms involved in HOPs' transplacental transport.

Methoxylated polybrominated diphenyl ethers (MeO-PBDEs), a type of emerging environmental contaminants, can accumulate through the food chain and eventually enter the human body. For pregnant women, these chemicals may be transplacentally transported to their fetuses, causing early intrauterine exposure. This study was designed to explore the transport process and characteristics of MeO-PBDEs using a BeWo cell monolayer model to simulate the placental barrier effect. Concentration-dependent transplacental transport indicates that the transport of MeO-PBDEs may be dominated by passive diffusion within the studied concentration range. According to the apparent permeability coefficients, MeO-BDE congeners investigated can be classified as poorly transported compounds, with the exception of MeO-BDE28. Time-dependent transplacental transport was observed (R-2 = 0.97-0.99), which showed that the intracellular accumulation of MeO-PBDEs followed pseudo-first-order kinetics process. The transport process of MeO-PBDEs in the BeWo cell assay was not found to be sensitive to the pH of 6.5-7.4. An efflux transporter, breast cancer resistance protein, may be involved in the transport process of some MeO-PBDE congeners, and influx transporters, including organic anion transporters and organic cation transporters, may also be involved in the transport process. Although the present results indicated the possible transplacental transport mechanism, more molecular biological studies should be conducted to advance the understanding of the transport mechanisms. (C) 2020 Elsevier Ltd. All rights reserved.

Objective·To investigate whether paraoxonase 1 (PON1) genotypes were effect modifiers in the relationship between exposure to organophosphate pesticides (Ops) and oxidative stress level in pregnant women.Methods · A total of 204 pregnant women recruited from a hospital in Shandong Province were included in the study.Four nonspecific dialkyl phosphate (DAP) metabolites of Ops were measured in each urine sample.Levels of two oxidative stress biomarkers [total free sulfhydryl (-SH) and malondialdehyde (MDA)] were measured in serum samples.Blood samples were also analyzed for detecting PON1 genotypes (PONI-108,PON1192 and PON155).Separate linear regression models were conducted to explore the relationship between DAP metabolite levels and oxidative stress levels in all 204 pregnant women or women within each PON1 genotype.Results· There was no significant association between DAP metabolite levels and oxidative stress levels in all 204 women.Levels of dimethyl phosphates [β (95％ CI):-104.10 (-191.31,-16.88)] and dialkyl phosphates [f (95％ CI):-111.78 (-221.84,-1.72)] were negatively associated with-SH level among pregnant women with PON1192RR genotype,but this association was not found among women with other genotypes.Conclusion· OP exposure may be associated with a higher oxidative stress level among pregnant women with PONI192RR genotype.