Predicting the Activity of Unidentified Chemicals in Complementary Bioassays from the HRMS Data to Pinpoint Potential Endocrine Disruptors.

The majority of chemicals detected via nontarget liquid chromatography high-resolution mass spectrometry (HRMS) in environmental samples remain unidentified, challenging the capability of existing machine learning models to pinpoint potential endocrine disruptors (EDs). Here, we predict the activity of unidentified chemicals across 12 bioassays related to EDs within the Tox21 10K dataset. Single- and multi-output models, utilizing various machine learning algorithms and molecular fingerprint features as an input, were trained for this purpose. To evaluate the models under near real-world conditions, Monte Carlo sampling was implemented for the first time. This technique enables the use of probabilistic fingerprint features derived from the experimental HRMS data with SIRIUS+CSI:FingerID as an input for models trained on true binary fingerprint features. Depending on the bioassay, the lowest false-positive rate at 90% recall ranged from 0.251 (sr.mmp, mitochondrial membrane potential) to 0.824 (nr.ar, androgen receptor), which is consistent with the trends observed in the models' performances submitted for the Tox21 Data Challenge. These findings underscore the informativeness of fingerprint features that can be compiled from HRMS in predicting the endocrine-disrupting activity. Moreover, an in-depth SHapley Additive exPlanations analysis unveiled the models' ability to pinpoint structural patterns linked to the modes of action of active chemicals. Despite the superior performance of the single-output models compared to that of the multi-output models, the latter's potential cannot be disregarded for similar tasks in the field of in silico toxicology. This study presents a significant advancement in identifying potentially toxic chemicals within complex mixtures without unambiguous identification and effectively reducing the workload for postprocessing by up to 75% in nontarget HRMS.

Evaluation of an imaging-based in vitro screening platform for estrogenic activity with OECD reference chemicals.

Estrogen receptor alpha (ERα) is often a primary target of endocrine disrupting chemicals (EDCs) and therefore several biochemical and cell-based assays for the detection of chemicals with estrogenic properties have been developed in the past. However, the current approaches are not suitable for the monitoring of pathway activation dynamics, and they are mostly based on expression constructs that lack physiological promoter regulation. We recently developed MCF7 fluorescent reporter cell lines of 3 different green fluorescent protein (GFP)-tagged ERα target genes: GREB1, PGR and TFF1. These reporters are under control of the full physiological promoter region and allow the monitoring of dynamic pro-proliferative pathway activation on a single cell level using a live-cell imaging set-up. In this study, we systematically characterized the response of these reporters to a full reference compound set of known estrogenic and non-estrogenic chemicals as defined by the Organization for Economic Co-Operation and Development (OECD). We linked activation of the pro-proliferative ERα pathway to a potential adverse outcome by additionally monitoring cell cycle progression and proliferation. The correct classification of the OECD reference compounds showed that our reporter platform has the same sensitivity and specificity as other validated artificial ERα pathway reporters, such as the ERα CALUX and VM7 Luc ER TA assay. By monitoring several key events (i.e. ER target activation, cell cycle progression and proliferation), and subsequently determining Point-of-Departure (POD) values, our reporter panel can be used in high-throughput testing for a physiologically more relevant, quantitative temporal endocrine modulation analysis to improve human carcinogen risk assessment.

Estrogenic Activity of Tetrazole Derivatives Bearing Bisphenol Structures: Computational Studies, Synthesis, and In Vitro Assessment.

The classification of bisphenol A (BPA) as an industrial endocrine disruptor has led to a ban of this ubiquitous critical starting material from food and medical applications. Thus, scientists worldwide are researching to develop non-ER binding starting compounds to fulfill unmet market needs. In line with this trending research topic, the current paper highlights the development of tetrazole derivatives bearing a bisphenol structure (TbB) as a novel weak binder or potential inactive to the estrogen receptor (ER) and androgen receptor (AR). The structure and ligand-based approach supported by binding affinity analysis, electrostatic complementarity, ADMET prediction, and in silico studies identified TbBs as privileged substitutes for BPA. Five TbB ligands were successfully synthesized and subjected to biological testing comprising radioligand competitive binding and functional cellular assays. The measured IC50 value for BPA was found to be 0.24 µM, whereas all the inhibitions were less than 15% for the two TbB ligands, 223-2 and 223-3. As these TbB ligands did not meet the established acceptance criteria of 50% inhibition, they are considered as extremely weak binders to ERα. Steric clashes, the desolvation effect, and the increased total polar surface area (TPSA) of TbB ligands in the hydrophobic binding site are hypothesized to be possible reasons for low binding. Modeling studies complemented by bioassays highlight TbB compounds as privileged prospective BPA replacements. However, more research on TbB ligand toxicity is needed to understand and substantiate that the adverse effects on the hormonal system, for example, via metabolic activation, are not elicited.

A novel method for rapid and quantitative detection of bisphenol A in urine.

Bisphenol A (BPA) is classified as an endocrine disruptor (ED) and it can interact with variety of hormone receptors leading to hormonal disruption and increased risk of various adverse health effects. Reducing human exposure to BPA is one of the main challenges of public health, as it is constantly present in daily life. A low-cost and commonly applied method to enable determination of BPA in the patient's body has yet to be developed. Currently available techniques are expensive, time-consuming, and require access to highly equipped analytical chemistry laboratories. Here we describe a fast and cheap engineered lateral flow assay of our design, to detect of BPA in urine samples. The technology not only provides an opportunity to perform rapid medical diagnostics without the need for an access to the central laboratory but also a means for self-diagnosis by the patient. The addition of ß-glucuronidase improves the sensitivity of detection as it releases the free BPA from glucuronide complexes in urine. This invention may become a demonstrated analytical means for lowering human exposure to BPA and probably also to other EDs and consequently, may be useful in decrease of the risk for several lifestyle diseases.

In vitro assessment of corticosteroid effects of eight chiral herbicides.

Information regarding the enantioselective endocrine disruption of chiral herbicides is scarce. This study assessed the disrupting effects of eight typical chiral herbicides on corticosteroids (including glucocorticoids and mineralocorticoids). Enantioselectivity of eight chiral herbicides were evaluated for their agonistic/antagonistic effects on glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) with CHOK1 cell line using reporter gene assay. Their influence on the production of corticosteroids were further investigated in H295R cell line using enzyme-linked immunosorbent assay (ELISA). None of the racemates or enantiomers of eight chiral herbicides exhibited GR or MR agonistic activity at non-cytotoxic concentrations. However, rac-propisochlor and S-imazamox antagonized cortisol-induced transactivation of GR by 21.79% and 38.73% at the concentration of 1.0 × 10-7 M and 1.0 × 10-6 M, respectively, and R-napropamide remarkably attenuated aldosterone-induced MR transactivation by 68.78% at 1.0 × 10-6 M. The secretion of cortisol was significantly restrained after treated with 1.0 × 10-6 M rac-propisochlor and rac-/R-napropamide at the concentration of 1.0 × 10-6 M by 26.49%, 30.10% and 35.27%, respectively, while this glucocorticoid was remarkably induced by 1.0 × 10-5 M rac-diclofop-methyl and its two enantiomers at the concentration of 1.0 × 10-5 M by 75.60%, 100.1% and 68.78%, respectively. Exposure to rac-propisochlor (1.0 × 10-6 M), S-diclofop-methyl (1.0 × 10-5 M) or rac-/S-/R- acetochlor (1.0 × 10-6 M) and rac-/S-/R-lactofen (1.0 × 10-6 M) inhibited the secretion of aldosterone by approximately 40%. Our findings suggested that chiral herbicides disrupted corticosteroid homeostasis in an enantioselective way. Therefore, more comprehensive screening is required to better understand the ecological and health risks of chiral pesticides.

Assessment of the endocrine-disrupting effects of organophosphorus pesticide triazophos and its metabolites on endocrine hormones biosynthesis, transport and receptor binding in silico.

Triazophos (TAP) was a widely used organophosphorus insecticide in developing countries. TAP could produce specific metabolites triazophos-oxon (TAPO) and 1-phenyl-3-hydroxy-1,2,4-triazole (PHT) and non-specific metabolites diethylthiophosphate (DETP) and diethylphosphate (DEP). The objective of this study involved computational approaches to discover potential mechanisms of molecular interaction of TAP and its major metabolites with endocrine hormone-related proteins using molecular docking in silico. We found that TAP, TAPO and DEP showed high binding affinity with more proteins and enzymes than PHT and DETP. TAP might interfere with the endocrine function of the adrenal gland, and TAP might also bind strongly with glucocorticoid receptors and thyroid hormone receptors. TAPO might disrupt the normal binding of androgen receptor, estrogen receptor, progesterone receptor and adrenergic receptor to their natural hormone ligands. DEP might affect biosynthesis of steroid hormones and thyroid hormones. Meanwhile, DEP might disrupt the binding and transport of thyroid hormones in the blood and the normal binding of thyroid hormones to their receptors. These results suggested that TAP and DEP might have endocrine disrupting activities and were potential endocrine disrupting chemicals. Our results provided further reference for the comprehensive evaluation of toxicity of organophosphorus chemicals and their metabolites.

Assessment of endocrine disruptor effects of levonorgestrel and its photoproducts: Environmental implications of released fractions after their photocatalytic removal.

The presence of levonorgestrel (LNG) in water bodies via direct discharge and human excretion has been reported worldwide, but its effects on the reproduction of aquatic species and humans are still unknown. Owing to its recalcitrant properties, LNG is not completely removed during wastewater treatment plants, and many species may be exposed to low traces of this compound from discharged effluents. Thus, in this study, a photocatalytic process for removing LNG along with screening of endocrine disruptor effects for risk assessment was applied. Although the removal rate of LNG by ultraviolet C (UV-C) radiation was >90%, reproductive toxicity testing using the BeWo cell line exposed to LNG and its degraded fraction showed the reduced production of basal human chorionic gonadotropin hormone (ß-hCG) by more than 73%, from 8.90 mIU mL-1 to <2.39 mIU mL-1, with both LNG and the degraded fraction. ß-hCG hormone has been implicated in the viability of trophoblastic cells during the first trimester of pregnancy; therefore, degraded fractions and waterborne LNG may affect reproduction in some aquatic species and humans with low level of exposure.

Multi-phase distribution and risk assessment of endocrine disrupting chemicals in the surface water of the Shaying River, -Huai River Basin, China.

Herein we investigated the multi-phase distribution and estrogenic effects of endocrine disrupting chemicals (EDCs) in suspended particulate matter (SPM), colloids, and soluble phases from the Shaying River to assess the composition of estrogenic compounds and associated estrogenic risk. The yeast two hybrid (YES) method, cross-flow ultrafiltration (CFUF), and LC-MS/MS were employed. Risk quotient (RQ) values ranged from 0.72 to 3.88, revealing that the Shaying River posed high estrogenic risk to aquatic organisms. The contribution ratios of the target EDCs to the EEQYES ranged from 62.7% to 92.5%, indicating that these chemicals were major contributors of estrogenic effects in the Shaying River. Further, 54.0-77.8% of the detected EDCs were distributed in the soluble phase, 15.1-31.7% were bound to colloidal substances, and 3.90-19.4% EDCs were associated with SPM. Significant correlation between total EDC abundance and COD contents was detected, and the concentrations of endogenous estrogens (E1, E2, and E3) were positively correlated with total nitrogen (TN) and total phosphorus (TP). In addition, the in-situ SPM-soluble (Kpoc) and colloid-soluble partition (Kcoc) coefficients were calculated. The log Kpoc values of target compounds varied from 4.10 to 5.19, while log Kcoc values ranged from 4.25 to 5.56. Their Kcoc values were larger than the Kpoc values, indicating that organic colloids were the most important carriers of EDCs in the aquatic environment.

Assessment of bisphenol A alternatives in paper products from the Chinese market and their dermal exposure in the general population.

Bisphenol A (BPA), a well-known endocrine disruptor, is used as a color developer in thermal paper. More recently, some emerging structural analogues have been introduced to replace BPA due to the strengthened regulations concerning thermal paper. Nevertheless, very limited data are available regarding their occurrence and potential health risks. Here, thirteen potentially toxic compounds were investigated in paper products (120 thermal papers and 81 nonthermal papers) collected in Beijing, China. The results indicated that the replacement of BPA by alternatives such as Bisphenol S (BPS), Bis(2-chloroethyl)ether-4,4″-dihydroxydiphenyl sulfone copolymer (D-90), 4-hydroxyphenyl 4-isoprooxyphenylsulfone (D-8), Bis(4-hydroxyphenyl)sulfonylphenyl (BPS-MAE) and Bis-(3-allyl-4-hydroxyphenyl) sulfone (TGSA) has been significantly advanced in several types of thermal paper (i.e., market weight stickers, train tickets, express labels, air boarding passes and lottery tickets). The mean value for the total analyte concentrations in thermal paper was 6.06 mg/g, and the highest level found was 26.0 mg/g. In addition, the frequent detection of these chemicals in nonthermal paper (>80%, n = 81) demonstrated that the contamination in thermal paper can be spread into other recycled paper, such as corrugated boxes, newspapers, food contact papers, etc. The estimated daily intake of BPA and its alternatives through the handling of thermal paper was 0.025 µg/kg bw/day for the general population. This is the first report on the occurrence of various new BPA alternatives in paper products from China, which will be helpful for further risk assessment and making responsible replacement decisions.

Solar reclamation of wastewater effluent polluted with bisphenols, phthalates and parabens by photocatalytic treatment with TiO2/Na2S2O8 at pilot plant scale.

Investigations of anthropogenic contaminants in fresh- and wastewater have shown a wide variety of undesirable organic compounds such as Endocrine Disruptors (EDs). As a result, wastewater treatments using innovative technologies to remove those organic compounds are required. In this paper, the photodegradation of six EDs in wastewater at pilot plant scale is reported. The EDs were bisphenol A, bisphenol B, diamyl phthalate, butyl benzylphthalate, methylparaben and ethylparaben. Commercial TiO2 nanopowders (P25, Alfa Aesar and Kronos vlp 7000) were used as photocatalysts. The operating variables (type and loading catalyst, effect of electron acceptor and pH) were previously optimized under laboratory conditions. The results show that the use of TiO2 alongside an electron acceptor like Na2S2O8 strongly enhances the degradation rate of the studied compounds compared with photolytic tests, especially P25. The oxidation rates of the EDs at pilot plant scale were calculated following the disappearance of the target compound as a function of fluence (H). The ED degradation followed a pseudo-first order kinetics in all cases. In our experimental conditions, the half-fluence (H50) varied from 79 to 173 J cm-2 (photolytic test), 10-117 J cm-2 (TiO2 vlp 7000) and 3-58 J cm-2 (TiO2 P25), for bisphenol B and butyl benzylphthalate, respectively. It is concluded that solar photocatalysis using the tandem TiO2/Na2S2O8 can be considered as an environmental-friendly tool for water detoxification and a sustainable technology for environmental remediation, especially in the Mediterranean Basin, where many places receive more than 3000 h of sunshine per year. Although the cost depends on the nature of the pollutant, the treatment cost was estimate to be about 150 € m-3 for photocatalytic treatment with TiO2 P25.

Assessment of the Effects of Endocrine Disrupting Compounds on the Development of Vertebrate Neural Network Function Using Multi-electrode Arrays.

Bis-phenols, such as bis-phenol A (BPA) and bis-phenol-S (BPS), are polymerizing agents widely used in the production of plastics and numerous everyday products. They are classified as endocrine disrupting compounds (EDC) with estradiol-like properties. Long-term exposure to EDCs, even at low doses, has been linked with various health defects including cancer, behavioral disorders, and infertility, with greater vulnerability during early developmental periods. To study the effects of BPA on the development of neuronal function, we used an in vitro neuronal network derived from the early chick embryonic brain as a model. We found that exposure to BPA affected the development of network activity, specifically spiking activity and synchronization. A change in network activity is the crucial link between the molecular target of a drug or compound and its effect on behavioral outcome. Multi-electrode arrays are increasingly becoming useful tools to study the effects of drugs on network activity in vitro. There are several systems available in the market and, although there are variations in the number of electrodes, the type and quality of the electrode array and the analysis software, the basic underlying principles, and the data obtained is the same across the different systems. Although currently limited to analysis of two-dimensional in vitro cultures, these MEA systems are being improved to enable in vivo network activity in brain slices. Here, we provide a detailed protocol for embryonic exposure and recording neuronal network activity and synchrony, along with representative results.

Regulatory identification of BPA as an endocrine disruptor: Context and methodology.

BPA is one of the most investigated substances for its endocrine disruptor (ED) properties and it is at the same time in the center of many ED-related controversies. The analysis on how BPA fits to the regulatory identification as an ED is a challenge in terms of methodology. It is also a great opportunity to test the regulatory framework with a uniquely data-rich substance and learn valuable lessons for future cases. From this extensive database, it was considered important to engage in a detailed analysis so as to provide specific and strong evidences of ED while reflecting accurately the complexity of the response as well the multiplicity of adverse effects. An appropriate delineation of the scope of the analysis was therefore critical. Four effects namely, alterations of estrous cyclicity, mammary gland development, brain development and memory function, and metabolism, were considered to provide solid evidence of ED-mediated effects of BPA.

Risk assessment of the endocrine-disrupting effects of nine chiral pesticides.

The increased release of chiral pesticides into the environment has generated interest in the role of enantioselectivity in the environmental fate and ecotoxicological effects of these compounds. However, the information on the endocrine disrupting effects (EDEs) of chiral pesticides is still limited and discrepancies are also usually observed among different assays. In this study, we investigated the enantioselectivity of EDEs via estrogen and thyroid hormone receptors for nine chiral pesticides using in vitro and in silico approaches. The results of the luciferase reporter gene assays showed 7 chiral pesticides possessed enantioselective estrogenic activities and 2 chiral pesticides exerted thyroid hormone antagonistic effects. Proliferation assays in MCF-7 and GH3 cells were also used to verify the results of the dual-luciferase reporter gene assays. At last, the molecular docking results indicated that the enantioselective EDEs of chiral pesticides were partially due to enantiospecific binding affinities with receptors. Our data not only show enantioselective EDEs of nine chiral pesticides, but also would be helpful to better understanding the molecular biological mechanisms of enantioselectivity in EDEs of chiral pesticides.

Parallel assessment of the effects of bisphenol A and several of its analogs on the adult human testis.

STUDY QUESTION: Are bisphenol A (BPA) and BPA analogs (BPA-A) safe for male human reproductive function? SUMMARY ANSWER: The endocrine function of human testes explants [assessed by measuring testosterone and insulin-like factor 3 (INSL3)] was impacted by exposure of the human adult testis explants to BPA/BPA-A. WHAT IS KNOWN ALREADY: The few epidemiologic studies performed suggest that bisphenols have potential endocrine disruptive properties, but they did not identify clear and direct patterns of endocrine disruption. STUDY DESIGN, SIZE, DURATION: Adult human testis explants in culture were exposed to BPA and the analogs bisphenol F (BPF), bisphenol S (BPS), bisphenol E (BPE), bisphenol B (BPB) and bisphenol A diglycidyl ether (BADGE) at 10-9-10-5 M for 24 or 48 h. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human adult testes were obtained from prostate cancer patients who had no hormone therapy, or from multiorgan donors. After ex vivo exposure to the investigated bisphenols, the measured outcomes were related to histopathology (gross morphology and germ cell viability determined by anti-caspase three immunohistochemistry), and the levels of testosterone, INSL3 and inhibin B were measured using immunoassays. The levels of mRNA encoding key enzymes of bisphenol biotransformation were investigated by quantitative PCR: UGT2B15 UDP (glucuronosyltransferase two family, polypeptide B15), GUSB (glucuronidase beta), SULT1A1 and 3 (sulfotransferase family 1 A member 1 and 3) and STS (steroid sulfatase). MAIN RESULTS AND THE ROLE OF CHANCE: A significant dose-dependent inhibition was found between testosterone levels measured in the culture medium and concentrations of BPA (P = 0.00778 at 24 h and P = 0.0291 at 48 h), BPE (P = 0.039) and BPF (P = 0.00663). The observed BPA and BPA-A-induced inhibition of testosterone production varied according to duration of exposure and BPA/BPA-A concentrations. BPA (10-9 M; P < 0.05), BPB (10-9 M; P < 0.05), BPS (10-9 and 10-8 M; P < 0.05) and BADGE (10-5 M; P < 0.05) increased Leydig cell INSL3 production. By contrast, BPE dose dependently inhibited INSL3 (P = 0.0372). Conversely, Sertoli cell function (inhibin B) and germ cell viability were not significantly affected by either bisphenols. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Environmental compounds cannot be deliberately administered to men, justifying the use of an ex vivo approach. A relatively low number of testes samples were available for analysis (n = 3, except for testosterone secretion with n = 5). The active concentrations of BPA and BPA-A used in the study were higher than those found in human biological fluids. WIDER IMPLICATIONS OF THE FINDINGS: Under our experimental conditions, direct exposure to BPA or BPA-A can result in endocrine disturbance in the adult human testis. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Inserm (Institut National de la Santé et de la Recherche Médicale), EHESP-School of Public Health, University of Rennes1, by grants from the Agence Nationale de la Recherche (ANR; grant#ANR-13-CESA-0012-03 NEWPLAST) and Agence Nationale de Sécurité Sanitaire de l'Alimentation, de l'Environnement et du Travail (ANSES; grant#EST-2010/2/046 (BPATESTIS)). All authors declare they have no current or potential competing financial interests.

Population Exposure to Phthalate-containing Drugs.

Phthalates are known endocrine disruptors. Not commonly recognized, phthalates are used as excipients in a number of drug formulations. We aimed to describe the sale of phthalate-containing drugs in Denmark from 2004 to 2015. National data on annual sale of medications (tablets only) were accessed from medstat.dk. Data from the Danish Medicines Agency on phthalate content per tablet were merged with data on total sale for each active substance and drug formulation. We used the 'defined daily dose' (DDD) as the unit of sale and calculated the total amount of phthalate (mg) dispensed per 1000 inhabitants. Specific tablet content was compared with the maximum daily exposure limits defined by regulatory agencies for diethyl phthalate (DEP) and dibutyl phthalate (DBP) of 4.0 and 0.01 mg/kg/day, respectively. Use of phthalate-containing drugs in Denmark was common. We found 154 drug products containing five different phthalates. Two low-molecular-weight phthalates and three high-molecular-weight phthalates were identified, with a total sale of 59.4 and 112 DDD per 1000 inhabitants per day during the study period, respectively. The highest amount of DBP was found in multi-enzymes (24.6-32.8 mg per DDD) and mesalazine (12.5-26.4 mg per DDD). Budesonide, lithium and bisacodyl also exceeded the DBP exposure limit of 0.01 mg/kg/day. Other drugs had high levels of DEP, although not exceeding the exposure limit. Sales of phthalate-containing drugs in Denmark from 2004 to 2015 were substantial, and phthalate exposure from several products exceeded the regulatory exposure limit introduced in 2014.

Molecular interactions of dioxins and DLCs with the ketosteroid receptors: an in silico risk assessment approach.

Dioxins and dioxin-like compounds (DLCs) are the ones with poor water solubility and low volatility, resistant to physical, chemical and biological processes, persistent in the environment even under extreme conditions. Due to lipophilic nature, they get adhered to the fatty material and concentrate through biomagnification and bioaccumulation, thereby easily getting incorporated into food chains, paving the way to endocrine disruption via modulation of various human receptors. This in turn leads to certain adverse health effects. In the present study, a total of 100 dioxins and DLCs were taken and their binding pattern was assessed with the ketosteroid receptors, i.e. androgen (hAR), glucocorticoid (hGR), progesterone (hPR) and mineralocorticoid (hMR) in comparison to the corresponding natural steroids and a known endocrine disrupting xenobiotic, Bisphenol A (BPA). Most of the DLCs, particularly those bearing hydroxyl (-OH) group showed considerable affinities with ketosteroid receptors. On comparing D scores of all the dioxins and DLCs against all four receptors, compound 8-hydroxy-3,4-dichlorodibenzofuran(8-OH-DCDF) exhibited least D score of -9.549 kcal mol-1 against hAR. 3,8-Dihydroxy-2-chlorodibenzofuran(3,8-DiOH-CDF), 4'-hydroxy-2,3,4,5-tetrachlorobiphenyl (4'-OH-TCB) and 4-hydroxy-2,2',5'-trichlorobiphenyl(4-OH-TCB) also showed comparable molecular interactions with the ketosteroid receptors. These interactions mainly include H-bonding, π-π stacking, hydrophobic, polar and van der Waals' interactions. In contrast, BPA and some natural ligands tested in this study showed lower binding affinities with these receptors than certain DLCs reported herein, i.e. certain DLCs might be more toxic than the proven toxic agent, BPA. Such studies play a pivotal role in the risk assessment of exposure to dioxins and DLCs on human health.

Occurrence, fate, and risk assessment of selected endocrine disrupting chemicals in wastewater treatment plants and receiving river of Shanghai, China.

The occurrence and fate of five endocrine disrupting chemicals (EDCs), including nonylphenol (NP), 4-tert-octylphenol (4-t-OP), 4-tert-butylphenol (4-t-BP), bisphenol A (BPA) and norethindrone (NET) was investigated in four wastewater treatment plants (WWTPs) and receiving river (Suzhou River and Yangtze River) of Shanghai. Selected EDCs in WWTPs influents ranged from 1.02 to 3560 ng L-1, which dominated by NP and BPA. Target compounds detected in effluents were from N.D. to 1136 ng L-1, with NP as most prevalent. The removal rates of target compounds varied from negative of NET to 99 % of BPA. Except of NET, efficiently removal rates (>70 %) were observed in WWTPs. Biological treatment was the major removal stage of selected EDCs in WWTPs. Furthermore, the selected EDCs were detected from N.D. to 424 ng L-1 in receiving river. The correlation analysis suggested EDCs pollution in receiving river might be mainly contributed by WWTPs effluents. The risk quotient of NP (RQ > 1) was higher than any other pollutants, indicating its relatively higher potential risk for the aquatic organism. These results will provide significant background data to future EDCs pollution control and management in Shanghai, China.

Photodegradation of the UV filter ethylhexyl methoxycinnamate under ultraviolet light: Identification and in silico assessment of photo-transformation products in the context of grey water reuse.

To prevent water shortages in the future and to reduce domestic water consumption, decentralized grey water (GW) reuse has become increasingly important. This water has, however, to be free of pollutants. Conventional treatment of GW does not fully eliminate micropollutants such as the UV filter substance ethylhexyl methoxycinnamate (EHMC). EHMC, which is commonly used in sunscreens and personal care products, is an endocrine disruptor and shows potential to bioaccumulation, which is also reflected in its low water solubility. Photolysis has been proposed as an alternative treatment method for other micropollutants, but it is not clear yet whether it can also be used to eliminate EHMC. One goal of this study was to better understand the basic pathways involved in this process. It aimed to identify photo-transformation products (photo-TPs) by using, in the test conditions, an initial concentration of EHMC higher than those expected in the environment. Acetonitrile (ACN) was added in low concentrations to the aqueous solution to overcome the low aquatic solubility of EHMC. The influence of this co-solvent on the degradation kinetics was studied. The photolysis experiments were carried out using a medium pressure mercury lamp, which emits UV light in the range of 200-400nm. The quantum yield of the photolysis of EHMC was 0.0042 and 0.0023mol·Einstein-1 (for 0.2 and 0.5% ACN (v/v), respectively), and the relative and absolute UV photon fluxes were determined. HPLC was used to monitor the elimination kinetics of EHMC, which followed first-order kinetics. The results of LC-MSn analyses revealed that beside others, several oxidized and hydroxylized EHMC isomers were formed as photo-TPs in aqueous solution. Using a set of in silico quantitative structure-activity relationship (QSAR) models, this study also offered new insights concerning the environmental fate and toxicity of the TPs of EHMC.

Aqueous photodegradation of 4-tert-butylphenol: By-products, degradation pathway and theoretical calculation assessment.

4-tert-butylphenol (4-t-BP), an endocrine disrupting chemical, is widely distributed in natural bodies of water but is difficult to biodegrade. In this study, we focused on the transformation of 4-t-BP in photo-initiated degradation processes. The steady-state photolysis and laser flash photolysis (LFP) experiments were conducted in order to elucidate its degradation mechanism. Identification of products was performed using the GC-MS, LC-MS and theoretical calculation techniques. The oxidation pathway of 4-t-BP by hydroxyl radical (HO) was also studied and H2O2 was added to produce HO. 4-tert-butylcatechol and 4-tert-butylphenol dimer were produced in 4-t-BP direct photolysis. 4-tert-butylcatechol and hydroquinone were produced by the oxidation of HO. But the formation mechanism of 4-tert-butylcatechol in the two processes was different. The benzene ring was fractured in 4-t-BP oxidation process and 29% of TOC was degraded after 16h irradiation.

Distribution and risk assessment of suspected endocrine-disrupting pesticides in creek water of Mumbai, India.

The present study deals with the investigation of existing pollution levels and potential ecological risk assessment of endocrine-disrupting organochlorine and organophosphorous pesticide residues in the Vasai Creek water near Mumbai. The average concentration of α- and ß-endosulfan (137.75 ng·L(-1)) exceeds the chronic criteria level of α- and ß-endosulfan (6.5 ng·L(-1)) set by US EPA for freshwater aquatic organisms. The concentration levels of aldrin (75.31 ng·L(-1)), dieldrin (71.19 ng·L(-1)) and endrin (76.60 ng·L(-1)) was found to exceed the respective criteria levels of <0.13, 65.1, and 61 ng·L(-1) as set by US EPA for protection of freshwater aquatic organisms. In addition, the level of chlorpyrifos (208.77 ng·L(-1)) exceeds the recommended concentration value of <35 ng·L(-1) set by Ministry of Environment of British Colombia. The results of our study give an indication of probable ecotoxicological risk to the marine breeding organisms of creek.