First Insight into Fetal Exposure to Legacy and Emerging Plasticizers Revealed by Infant Hair and Meconium: Occurrence, Biotransformation, and Accumulation.

Epidemiological studies have demonstrated the embryonic and developmental toxicity of plasticizers. Thus, understanding the in utero biotransformation and accumulation of plasticizers is essential to assessing their fate and potential toxicity in early life. In the present study, 311 infant hair samples and 271 paired meconium samples were collected at birth in Guangzhou, China, to characterize fetal exposure to legacy and emerging plasticizers and their metabolites. Results showed that most of the target plasticizers were detected in infant hair, with medians of 9.30, 27.6, and 0.145 ng/g for phthalate esters (PAEs), organic phosphate ester (OPEs), and alternative plasticizers (APs), and 1.44, 0.313, and 0.066 ng/g for the metabolites of PAEs, OPEs, and APs, respectively. Positive correlations between plasticizers and their corresponding primary metabolites, as well as correlations among the oxidative metabolites of bis(2-ethylhexyl) phthalate (DEHP) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), were observed, indicating that infant hair retained the major phase-I metabolism of the target plasticizers. While no positive correlations were found in parent compounds or their primary metabolites between paired infant hair and meconium, significant positive correlations were observed among secondary oxidative metabolites of DEHP and DINCH in hair and meconium, suggesting that the primary metabolites in meconium come from hydrolysis of plasticizers in the fetus but most of the oxidative metabolites come from maternal-fetal transmission. The parent compound/metabolite ratios in infant hair showed a decreasing trend across pregnancy, suggesting in utero accumulation and deposition of plasticizers. To the best of our knowledge, this study is the first to report in utero exposure to both parent compounds and metabolites of plasticizers by using paired infant hair and meconium as noninvasive biomonitoring matrices and provides novel insights into the fetal biotransformation and accumulation of plasticizers across pregnancy.

Metabolomics perspectives into the co-exposure effect of polycyclic aromatic hydrocarbons and metals on renal function: A meet-in-the-middle approach.

Studies on the dose effects of kidney impairment and metabolomes in co-exposure to polycyclic aromatic hydrocarbons (PAHs) and metals are limited. We aimed to identify overall associations and metabolic perturbations in 130 participants (53 petrochemical workers and 77 controls) exposed to a PAHs-metals mixture in Southern China. The urinary 7 hydroxylated PAHs and 15 metal(loid)s were determined, and serum creatinine, beta-2 microglobulin, and estimated glomerular filtration rate were health outcomes. The liquid chromatography-mass spectrometry-based method was applied to serum metabolomics. Generalized weighted quantile sum (gWQS) regressions were used to estimate the overall dose-response relationships, and pathway analysis, "meet-in-the-middle" approach, and mediation effect analyses were conducted to identify potential metabolites and biological mechanisms linking exposure with nephrotoxic effects. Our results indicated that renal function reduction was associated with a PAHs-metals mixture in a dose-dependent manner, and 1-hydroxynaphthalene and copper were the most predominant contributors among the two families of pollutants. Furthermore, the metabolic disruptions associated with the early onset of kidney impairment induced by the combination of PAHs and metals encompassed pathways such as phenylalanine-tyrosine-tryptophan biosynthesis, phenylalanine metabolism, and alpha-linolenic acid metabolism. In addition, the specifically identified metabolites demonstrated excellent potential as bridging biomarkers connecting the reduction in renal function with the mixture of PAHs and metals. These findings shed light on understanding the overall associations and metabolic mechanism of nephrotoxic effects of co-exposure to PAHs and metals.

Bioaccumulation and biotransformation of 1,2-bis (2,4,6-tribromophenoxyethane) (BTBPE) and 1,2-dibromo-4-(1,2-dibromoethyl)-cyclohexane (TBECH) in zebrafish (Danio rerio).

Despite the increasing production, use, and ubiquitous occurrence of novel brominated flame retardants (NBFRs), little information is available regarding their fate in aquatic organisms. In this study, the bioaccumulation and biotransformation of two typical NBFRs, i.e., 1,2-bis (2,4,6-tribromophenoxyethane) (BTBPE) and 1,2-dibromo-4-(1,2-dibromoethyl)-cyclohexane (TBECH), were investigated in tissues of zebrafish (Danio rerio) being administrated a dose of target chemicals through their diet. Linear accumulation was observed for both BTBPE and TBECH in the muscle, liver, gonads, and brain of zebrafish, and the elimination of BTBPE and TBECH in all tissues followed pseudo-first-order kinetics, with the fastest depuration rate occurring in the liver. BTBPE and TBECH showed low bioaccumulation potential in zebrafish, with biomagnification factors (BMFs) < 1 in all tissues. Individual tissues' function and lipid content are vital factors affecting the distribution of BTBPE and TBECH. Stereoselective accumulation of TBECH enantiomers was observed in zebrafish tissues, with first-eluting enantiomers, i.e. E1-α-TBECH and E1-ß-TBECH, preferentially accumulated. Additionally, the transformation products (TPs) in the zebrafish liver were comprehensively screened and identified using high-resolution mass spectrometry. Twelve TPs of BTBPE and eight TPs of TBECH were identified: biotransformation pathways involving ether cleavage, debromination, hydroxylation, and methoxylation reactions for BTBPE and hydroxylation, debromination, and oxidation processes for TBECH. Biotransformation is also a vital factor affecting the bioaccumulation potential of these two NBFRs, and the environmental impacts of NBFR TPs should be further investigated in future studies. The findings of this study provide a scientific basis for an accurate assessment of the ecological and environmental risks of BTBPE and TBECH.

Maternal hair segments reveal metal(loid) levels over the course of pregnancy: a preliminary study in Southern China.

Characterization of metal(loid) variation during pregnancy and identification of the affecting factors are important for assessing pregnancy exposures in epidemiological studies. In this study, maternal hair was collected in three segments (each 3 cm) from pregnant women in Guangzhou, China. Ten metal(loid)s, including six essential trace metal(loid)s and four toxic trace metal(loid)s, were analyzed to investigate the levels of various metal(loid)s during pregnancy and the factors that influence them. Strong pairwise correlations were observed between manganese (Mn), cobalt (Co), and vanadium (V), between selenium (Se), arsenic (As), and antimony (Sb), and between cadmium (Cd) and lead (Pb). All metal(loid)s except for Se, Mn, and Co showed strong correlations among the three hair segments, and most of the metal(loid)s had good reproducibility, with intraclass correlation coefficients (ICCs) ranging from 0.510 to 0.931, except for As (ICC = 0.334), Mn (ICC = 0.231), and Co (ICC = 0.235). Zn levels decreased, while Sb increased, in maternal hair during pregnancy. Maternal sociodemographic characteristics and dietary intake affected metal(loid) levels in maternal hair. These results provide foundational data for using maternal hair segmental analysis to evaluate exposure variation to metal(loid)s during pregnancy and the potential factors associated with them.

Occurrence of liquid crystal monomers in indoor and outdoor air particle matters (PM10): Implications for human exposure indoors.

Liquid crystal monomers (LCMs) are potentially persistent, bioaccumulating, and toxic substances. However, limited data are available on the occurrence of LCMs in indoor and outdoor air particle matter (PM10) in residential areas. Herein, residential areas near an e-waste dismantling center (Guiyu Town, Shantou City), as well as areas away from the e-waste site (Jiedong District, Jieyang City) were selected as the sampling areas. PM10 was collected from the indoor environments of Guiyu (IGY) and Jieyang (IJY), as well as those from the outdoor environments (OGY and OJY) using the high-volume air samplers (TH-10000C). The levels of 57 LCMs in PM10 were analyzed, and the highest concentrations of LCMs were found in IGY (0.970-1080 pg/m3), followed by IJY (2.853-455 pg/m3), OGY (0.544-116 pg/m3) and OJY (0.258-35.8 pg/m3). No significant difference was observed for LCM levels in indoor PM10 between the two areas (p > 0.05), which were significantly higher than those in outdoors (p < 0.05), indicating that the release of electronic products in general indoor environments is a source of LCMs that cannot be ignored. The compositions of LCMs in outdoors were not consistent with those of indoors. The correlation analysis of individual LCMs suggested potential different sources to the LCMs in indoor and outdoor environments. The median daily intake values of Σ46LCMs via inhalation were estimated as 0.440, 1.46 × 10-2, 0.170 and 1.19 × 10-2 ng/kg BW/day for adults, and as 2.27, 2.60 × 10-2, 0.880 and 2.10 × 10-2 ng/kg BW/day for toddlers, respectively, indicating much higher exposure doses of LCMs indoors compared with the outdoors, and much higher doses for toddlers compared with adults (p < 0.05). These results reveal the potentially adverse effects of LCMs on vulnerable populations, such as toddlers, in indoor environments.

Development and validation of an HPLC-MS/MS method for the simultaneous analysis of volatile organic compound metabolites, hydroxylated polycyclic aromatic hydrocarbons, and 8-hydroxy-2'-deoxyguanosine in human urine.

Humans are widely and concurrently exposed to volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs). However, few studies have reported the internal co-exposure levels of these chemicals in occupational and general populations. Specifically, the associations revealed between the urinary levels of metabolites of VOCs (mVOCs), hydroxylated PAHs (OH-PAHs), and oxidative stress biomarkers for humans remain limited. In this study, a method based on solid-phase extraction (SPE) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed for the simultaneous analysis of 22 mVOCs, 12 OH-PAHs, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in human urine samples. The method was validated with all target analyte accuracies and precisions in the range of 76 %-120 % and 1 %-14 % at three levels of spiked urine samples, respectively. The limit of detection (LOD) and limit of quantification (LOQ) of the target analytes were 0.01-0.34 ng/mL and 0.01-7.57 ng/mL, respectively. And the method was applied to measure urinary levels of target analytes from 38 petrochemical workers in Guangzhou, South China. Except for 3-hydroxy-benzo[a]pyrene, all target analytes were detected in the urine samples. The average levels were 0.05-12.6 ng/mL for individual OH-PAHs, 0.20-73620 ng/mL for individual mVOCs, and 1.00 ng/mL for 8-OHdG. Additionally, 3-hydroxy-phenanthrene, 1-hydroxy-pyrene, 6-hydroxy-chrysene, N-acetyl-S-(trichlorovinyl)-L-cysteine, 2-methylhippuric acid, thiodiacetic acid, trans, trans-Muconic acid, and N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine had statistically significant positive effects on 8-OHdG levels, while 1-hydroxy-naphthalene, 1,2-dihydroxybenzene, and hippuric acid showed a negative effect on 8-OHdG, indicating these metabolites could lead to synergistic or antagonistic oxidative DNA damage. This study provides a robust analytical method that permits a comprehensive assessment of co-exposure to PAHs and VOCs and their potential adverse health effects.

Fetal exposure to organic contaminants revealed by infant hair: A preliminary study in south China.

Fetal exposure to multiple organic contaminants (OCs) is a public concern because of the adverse effects of OCs on early life development. Infant hair has the potential to be used as an alternative matrix to identify susceptible fetuses, owing to its reliability, sensitivity, and advantages associated with sampling, handling, and ethics. However, the applicability of infant hair for assessing in utero exposure to OCs is still limited. In this study, 57 infant hair samples were collected in Guangzhou, South China, to evaluate the levels and compositions of typical OCs in the fetus. Most of the target OCs were detected in infant hair, with medians of 144 µg/g, 17.7 µg/g, 192 ng/g, 46.9 ng/g, and 1.36 ng/g for phthalate esters (PAEs), alternative plasticizers (APs), organophosphorus flame retardants (OPFRs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs), respectively. Meanwhile, paired maternal hair (0-9 cm from the scalp) was collected to examine the associations between maternal and infant hair for individual compounds. Low-brominated PBDEs tended to deposit in infant hair, with median concentrations approximately two times higher than those in maternal samples. Levels of PBDEs and 4,4'-dichlorodiphenyldichloroethylene (p,p'-DDE) in paired maternal and infant hair showed strong positive correlations (p < 0.05), while most plasticizers (PAEs and APs) were poorly correlated between paired hair samples. Exposure sources were responsible for the variation in correlation between OC levels in the paired infant and maternal samples. Crude relationships between fetal exposure to OCs and birth size were examined using the Bayesian kernel machine regression (BKMR) model. BDE-28 was found to be adversely associated with the birth size. This study provides referential information for evaluating in utero exposure to OCs and their health risks based on infant hair.

The accumulation of organic contaminants in hair with different biological characteristics.

Human hair has increasingly been used as a noninvasive biomonitoring matrix for assessment of human exposure to various organic contaminants (OCs). However, the accumulation processes of OCs in hair remains unclear thus far, which raised concerns on the reliability of hair analysis results for OCs. Herein, Chinese population was selected as the study subject, the effects of changes in hair biological characteristics, including length and color, on the accumulation of OCs in hair was investigated. With the growing of hair shaft and the increased distance from the scalp, a significant increasing trend was found for levels of polychlorinated biphenyls (PCBs) and organophosphate flame retardants (PFRs) along the hair shafts (p < 0.05). Source identification using Chemical Mass Balance model indicated that PCBs in hair were mainly from exogenous sources (air and dust). The accumulation rates of PCB and PFR individuals in the hair shaft decreased with increasing of log Kow values. Additionally, the levels of OCs in hair decreased with the change in color from black to white, probably because of the loss of melanin in white hair. The ratios (R) of Cblack/Cwhite were significantly correlated with the log Kow values for individual chemicals (p < 0.05), implying that OCs with high log Kow values tend to accumulate more readily in black hair. The results of this study demonstrated the growth and change in colors of hair, as well as the physicochemical properties of chemicals, play vital roles in the accumulation of OCs in hair. The present study provides fundamental basis for the precise assessment of human exposure to OCs using hair as a biomonitoring matrix in future studies.

Analysis of polybrominated diphenyl ethers, hexabromocyclododecanes, and legacy and emerging phosphorus flame retardants in human hair.

Human hair has been identified as a non-invasive alternative matrix for assessing the human exposure to specific organic contaminants. In the present study, a solvent-saving analytical method for the simultaneous determination of 8 polybrominated diphenyl ethers (PBDEs), 3 hexabromocyclododecanes (HBCDDs), 12 phosphorus flame retardants (PFRs), and 4 emerging PFRs (ePFRs) has been developed and validated for the first time. Hair sample preparation protocols include precleaning with Milli-Q water, digestion with HNO3/H2O2 (1:1, v/v), liquid-liquid extraction with hexane:dichloromethane (4:1, v/v), and fractionation and cleanup on a Florisil cartridge. The method was validated by using two levels of spiked hair samples of 3 replicates for each spiking group. Limits of quantification (LOQs) were 0.12-22.4 ng/g for all analytes, average values of accuracies were ranging between 88 and 115%, 82-117%, 81-128%, and 81-95% for PBDEs, HBCDDs, PFRs, and ePFRs, respectively; and precision was also acceptable (RSD < 20%) for all analytes. Eventually, this method was applied to measure the levels of the targeted analytes in hair samples of e-waste dismantling workers (n = 14) from Qingyuan, South China. Median values ranged between 3.00 and 18.1 ng/g for PBDEs, 0.84-4.04 ng/g for HBCDDs, 2.13-131 ng/g PFRs, and 1.49-29.4 ng/g for ePFRs, respectively. PFRs/ePFRs constitute the major compounds in human hair samples, implying the wide use of PFRs/ePFRs as replacements of PBDEs and HBCDDs, as well the potential high human exposure risks of PFRs/ePFRs. Overall, this work will allow to a comprehensive assessment of human exposure to multiple groups of FRs using hair as a non-invasive bioindicator.

Levels and sources of PBDEs and PCBs in human nails from e-waste, urban, and rural areas in South China.

Human nails have been increasingly used as a biomarker for human exposure to persistent organic pollutants (POPs). In the present study, the fingernails of e-waste-dismantling workers from Longtang town, Qingyuan city, rural residents from Shijiao town, Qingyuan city, and urban residents from Guangzhou city, respectively, were collected from South China to monitor the human burdens of polybrominated diphenyl ether (PBDEs) and polychlorinated biphenyl (PCBs). The median concentrations of in the nails of the e-waste-dismantling workers, and urban and rural residents were 412, 129, and 82.1 ng g-1, respectively, and the median concentrations of were 108, 8.4, and 22.1 ng g-1, respectively. The levels of PCBs and PBDEs in the nails of e-waste-dismantling workers were significantly higher as compared to those for urban and rural residents (p < 0.05), implying the continuous and greater exposure to these chemicals in the e-waste recycling areas. BDE 209 (92-98%) was the major congener of PBDEs and CB 52 (26-51%) was the main congener of PCB in nail samples. However, no significant gender difference was observed for PBDE and PCB levels in nails from all three investigated areas, and no significant correlation was found between their levels and the age of the participants. The enantiomer fractions (EFs) of CBs 95 and 132 indicated that the external sources (e.g. dust and/or air) were the primary sources for CBs 95 and 132 in human nails from the e-waste area, while the contribution from the internal sources (e.g. serum) could be in a small percentage. The results of this study indicate that human nails can be used as a proper indicator of human exposure to PCBs and PBDEs, and further studies are needed by a comprehensive investigation of the relationships between the PCB and PBDE levels in the nails and serum and/or other internal tissues.

Antibiotics in wastewater from multiple sources and surface water of the Yangtze River in Chongqing in China.

Antibiotic contamination attracts growing concerns because of their deleterious effects on the ecosystem and human health. In this study, 43 antibiotics in wastewater from a variety of sources and water of the Yangtze River in Chongqing City in western China were measured. Thirty compounds were detected, and their concentrations were highest in leachates from the municipal solid waste treatment facilities (landfills and incineration plants) with total concentrations of 3584-57,106 ng/L. The total concentrations in influents of municipal and industrial wastewater treatment plants (WWTPs) were comparable (401-7994 ng/L versus 640-8945 ng/L). The concentrations in raw sewage from swine farms (with a total of 10,219-39,195 ng/L) and poultry farms (1419-36,027 ng/L) were noticeably higher than those from other farms (54.0-5516 ng/L). Fluoroquinolones were the dominant antibiotics contributing over 50% in all the sources, and sulfonamides and imidazole fungicides contributed 3.2-34%, whereas tetracyclines and macrolides had minor contributions. The overall antibiotic removal rates were highest in solid waste treatment facilities (88% on average), comparable between municipal and industrial WWTPs (61%), and lowest in animal farms (39%). The mass loads to the investigated municipal WWTPs via influent wastewater ranged from 7.80 to 1531 kg/year (53.2-2482 µg/day per capital). The influent mass loads to the industrial WWTPs and farms were 3.7-50 kg/year and 0.9-5437 g/year, respectively. We estimated that the mass inventories of antibiotics from these sources to the environment via effluent discharges were approximately 2044 kg for municipal WWTPs, 61 kg for industrial WWTPs, and 34 kg for animal farms in the whole city. Antibiotic concentrations in the Yangtze River water were substantially low (< 492 ng/L, with a mean of 57.8 ng/L) suggesting dissipation during the movement.

Pyrene metabolites by bacterium enhancing cell division of green alga Selenastrum capricornutum.

Collaborations between multiple microbial species are important for understanding natural clearance and ecological effects of toxic organic contaminants in the environment. However, the interactions between different species in the transformation and degradation of contaminants remain to address. In this study, the effects of pyrene and its bacterial metabolites on the algal growth (Selenastrum capricornutum) were examined. The specific growth rate of algal cells incubated with bacterial pyrene metabolites (1.18 d-1) was highest among all treatment, followed by the controls (1.07 d-1), treated with pyrene-free bacterial metabolites (1.04 d-1) and those treated with pyrene (0.55 d-1). G1 phase is the key growth phase for the cells to synthesize biomolecules for subsequent cell division in the cell cycle. Approximately 76.9% of the cells treated with bacterial pyrene metabolites were at the G1 phase and significantly lower than those with the controls (85.3%), pyrene-free bacterial metabolites (85.5%) and pyrene treatment (92.5%). Transcriptomic analysis of algae showed that the expression of 47 ribosomal unigenes was down-regulated by 5 mg L-1 of pyrene, while 308 unigenes related to the preparation of cell division (DNA replication and protein synthesis) were up-regulated by bacterial pyrene metabolites. It indicated that basal metabolism associated with the growth and proliferation of algal cells could be significantly promoted by bacterial pyrene metabolites. Overall, this study suggests a close relationship between algae and bacteria in the transformation and ecological effects of toxic contaminants.

Natural Porphyrins Accelerating the Phototransformation of Benzo[a]pyrene in Water.

Phototransformation is one of the most important transformation pathways of organic contaminants in the water environment. However, how active compounds enable and accelerate the phototransformation of organic pollutants remains to be elucidated. In this study, the phototransformation of benzo[a]pyrene (BaP, the first class "human carcinogens") by various natural porphyrins under solar irradiation was investigated, including chlorophyll a, sodium copper chlorophyllin, hematin, cobalamin, and pheophorbide a. Transformation efficiency of BaP varied considerably with chemical stabilities of the porphyrins. Porphyrins with a lower stability displayed higher BaP transformation efficiencies. BaP transformation had a significant positive correlation with the production of singlet oxygen. Identical phototransformation products of BaP were observed for all investigated porphyrins, and the main products were identified as BaP-quinones, including BaP-1,6-dione, BaP-3,6-dione, and BaP-6,12-dione. The mechanism of natural porphyrins accelerating the BaP phototransformation in water was proposed to proceed via the photocatalytic generation of singlet oxygen resulting in the transformation of BaP to quinones.

Fully automatic single-drop microextraction with one-setp extraction and derivatization and its application for rapid analysis of hydroxylated polycyclic aromatic hydrocarbons in seawaters.

A fully automatic single-drop microextraction (SDME) coupled with gas chromatography/mass spectrometry (GC/MS) was developed for the determination of 12 hydroxylated metabolites of polycyclic aromatic hydrocarbons in seawaters. The derivatization reagent was added to the extraction solvent in order to realize one-step extraction and derivatization. High sensitivity of the method could be achieved after several parameters were optimized with the limit of detections (LODs) ranged from 0.33 to 7.50ngL-1 and RSDs less than 15%. Recoveries ranging from 68% to 128% was observed, and the proposed method was more acceptable than solid phase microextraction (SPME) in term of high sensitive, accurate and inexpensive. Moreover, it was found that most of the analytes could be described by the mass transfer kinetics except for 9-OH-fluo, because the mass transfer rate of 9-OH-fluo was faster than its derivatization rate. Hence, the concentration of TMS derivative of 9-OH-fluo was ignored in this study as it was determined by the reaction rate. Finally, the proposed method was successfully applied to determine the hydroxylated PAHs in surface and bottom sea waters collected from the Pearl River Estuaries, respectively. Most of the hydroxylated PAHs could be detected with the total concentrations ranging from 0.0387 to 1.0741µgL-1, and their spatial distribution was investigated by using spatial interpolation method of ordinary kriging in this study.