| 1. |
- Cao, Lin-Ying, et al.
(författare)
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Structure-dependent activity of polybrominated diphenyl ethers and their hydroxylated metabolites on estrogen related receptor gamma : in vitro and in silico study
- 2018
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 52:15, s. 8894-8902
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen-related receptor gamma (ERR gamma) is an orphan nuclear receptor having functional cross-talk with classical estrogen receptors. Here, we investigated whether ERR gamma is a potential target 8 of polybrominated diphenyl ethers (PBDEs) and their hydroxylated metabolites (OH-PBDEs). By using a fluorescence competitive binding method established in our laboratory, the binding potencies of 30 PBDEs/OH-PBDEs with ERR gamma were determined for the first time. All of the tested OH-PBDEs and some PBDEs bound to ERR gamma with K-d values ranging from 0.13-13.61 mu M. The OH-PBDEs showed much higher binding potency than their parent PBDEs. A quantitative structure-activity relationship (QSAR) model was developed to analyze the chemical binding potencies in relation to their structural and chemical characteristics. The QSAR model indicated that the molecular size, relative ratios of aromatic atoms, and hydrogen bond donors and acceptors were crucial factors for PBDEs/OH-PBDEs binding. By using a reporter gene assay, we found that most of the low-brominated PBDEs/OH-PBDEs exerted agonistic activity toward ERR gamma, while high-brominated PBDEs/OH-PBDEs had no effect on the basal ERR gamma activity. The docking results showed that the low-brominated PBDEs/OH-PBDEs tended to take an agonistic binding mode while the high-brominated ones tended to take an antagonistic binding mode. Overall, our results suggest ERR gamma to be a potential novel target for PBDEs/OH-PBDEs.
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| 2. |
- Du, Xinyu, et al.
(författare)
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Chlorinated Paraffins in Two Snake Species from the Yangtze River Delta : Tissue Distribution and Biomagnification
- 2020
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 54:5, s. 2753-2762
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Tidskriftsartikel (refereegranskat)abstract
- Very-short, short-, medium-, and long-chain chlorinated paraffins (vSCCPs, SCCPs, MCCPs, and LCCPs, respectively) were analyzed in different tissues of the terrestrial short-tailed mamushi (Gloydius brevicaudus) and the semi-aquatic red-backed rat snake (Elaphe rufodorsata) from the Yangtze River Delta, China. The total CP concentrations in liver, muscle, and adipose tissues in the two snake species were in the range of 2500-24 000, 4900-48 000, and 12-630 ng/g lw, respectively. Tissue burdens indicated that vSCCPs (C6-9) and SCCPs (C10-3) preferentially distributed to snake liver, while adipose was an important storage site and sink of MCCPs (C14-17) and LCCPs (C->18). On a lipid weight basis, vSCCPs and SCCPs were found in highest concentrations in red-backed rat snake liver and MCCPs and LCCPs in muscle, whereas for short-tailed mamushi, all CP groups were predominant in muscle, probably reflecting ecosystem/food web differences. Moreover, vSCCPs, SCCPs, MCCPs, and LCCPs were found to be biomagnified from black-spotted frogs to red-backed rat snakes with mean (maximum) biomagnification factors of 2.2 (3.4), 1.9 (3.7), 1.8 (2.8), and 1.7 (4.5), respectively. This is the first field study of biomagnification potential involving vSCCPs and LCCPs and highlights the need to include all CPs in studies.
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| 3. |
- Du, Xinyu, et al.
(författare)
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Evaluating oral and inhalation bioaccessibility of indoor dust-borne short- and median-chain chlorinated paraffins using in vitro Tenax-assisted physiologically based method
- 2021
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Ingår i: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 402
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Tidskriftsartikel (refereegranskat)abstract
- Though ingestion and inhalation of dust have been suggested as important exposure routes contributing chlorinated paraffins (CPs) build-up in humans, the bioaccessibility of dust-borne CPs in the organ environment has not been well-studied, which may hinder an accurate estimation of exposure risks. In this study, the ingestion and inhalation bioaccessibility of dust-borne shortand median-chain CPs (SCCPs and MCCPs) was assessed using (colon-extended) physiologically based extraction test with the addition of Tenax. The ingestion bioaccessibility of SCCPs 51.5 %Cl, SCCPs 63 %Cl, MCCPs 42 %Cl, and MCCPs 57 %Cl was in ranges of 21.1-44.0 %, 11.7-45.8 %, 21.9-36.6 %, and 7.9-32.9 %, respectively. Multiple linear regression analysis demonstrated statistically significant associations of ingestion bioaccessibility with carbon chain length and chlorine substitution. The ingestion bioaccessibility of CPs also increased with co-existence of carbohydrate/protein. The inhalation bioaccessibility of SCCPs (16.7-38.7 % in artificial lysosomal fluid and 15.5-34.1 % in modified Gamble solution) was significantly higher than MCCPs (< 5 %), and varied with dust particle size/total organic carbon content. Our study indicates that modest bioaccessible fractions of CPs in dust should be taken into account to refine the estimation of human exposure, and their bioaccessibility may be affected by CP molecular size, nutritional content and dust property.
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| 4. |
- Du, Xinyu, et al.
(författare)
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Tissue-Specific Accumulation, Sexual Difference, and Maternal Transfer of Chlorinated Paraffins in Black-Spotted Frogs
- 2019
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 53:9, s. 4739-4746
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Tidskriftsartikel (refereegranskat)abstract
- The restriction on usage of short-chain chlorinated paraffins (SCCPs) under Stockholm Convention may promote the production and application of medium chain chlorinated paraffins (MCCPs) and long chain chlorinated paraffins (LCCPs) as substitutes. This study focused on the tissue-specific exposure to SCCPs, MCCPs, and LCCPs in black-spotted frog, a prevalent amphibian species in the Yangtze River Delta, China. The total CP concentrations in frog liver, muscle, and egg samples ranged of 35-1200, 6.3-97, and 6.8-300 ng/g wet weight (ww), respectively. Livers and eggs contained primary SCCPs (on average 78%) while MCCPs (43%) together with SCCPs (41%) were dominant in muscles. A significantly negative correlation was observed between hepatosomatic index and CPs concentration in liver (p < 0.01), indicating that CP exposure may lower survival rates of frogs by suppressing the energy storage in liver. Additionally, maternal transfer, an important uptake pathway for CPs, was evaluated for the first time by calculating the ratios of CP levels in eggs to those in their paired liver tissues. The ratio of egg to liver for CP congener groups raised with the increasing of log K-ow values, indicating mother to egg transport of CPs was related to the lipophilicity of the chemicals.
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| 5. |
- Mansouri, Kamel, et al.
(författare)
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CoMPARA : Collaborative Modeling Project for Androgen Receptor Activity
- 2020
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Ingår i: Journal of Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 128:2, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Endocrine disrupting chemicals (EDCs) are xenobiotics that mimic the interaction of natural hormones and alter synthesis, transport, or metabolic pathways. The prospect of EDCs causing adverse health effects in humans and wildlife has led to the development of scientific and regulatory approaches for evaluating bioactivity. This need is being addressed using high-throughput screening (HTS) in vitro approaches and computational modeling.OBJECTIVES: In support of the Endocrine Disruptor Screening Program, the U.S. Environmental Protection Agency (EPA) led two worldwide consortiums to virtually screen chemicals for their potential estrogenic and androgenic activities. Here, we describe the Collaborative Modeling Project for Androgen Receptor Activity (CoMPARA) efforts, which follows the steps of the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP).METHODS: The CoMPARA list of screened chemicals built on CERAPP's list of 32,464 chemicals to include additional chemicals of interest, as well as simulated ToxCast (TM) metabolites, totaling 55,450 chemical structures. Computational toxicology scientists from 25 international groups contributed 91 predictive models for binding, agonist, and antagonist activity predictions. Models were underpinned by a common training set of 1,746 chemicals compiled from a combined data set of 11 ToxCast (TM)/Tox21 HTS in vitro assays.RESULTS: The resulting models were evaluated using curated literature data extracted from different sources. To overcome the limitations of single-model approaches, CoMPARA predictions were combined into consensus models that provided averaged predictive accuracy of approximately 80% for the evaluation set.DISCUSSION: The strengths and limitations of the consensus predictions were discussed with example chemicals; then, the models were implemented into the free and open-source OPERA application to enable screening of new chemicals with a defined applicability domain and accuracy assessment. This implementation was used to screen the entire EPA DSSTox database of similar to 875,000 chemicals, and their predicted AR activities have been made available on the EPA CompTox Chemicals dashboard and National Toxicology Program's Integrated Chemical Environment.
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| 6. |
- Xiao, Linhong, et al.
(författare)
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Studies of Emission Processes of Polymer Additives into Water Using Quartz Crystal Microbalance-A Case Study on Organophosphate Esters
- 2020
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 54:8, s. 4876-4885
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Tidskriftsartikel (refereegranskat)abstract
- Plastic materials contain various additives, which can be released during the entire lifespan of plastics and pose a threat to the environment and human health. Despite our knowledge on leakage of additives from products, accurate and rapid approaches to study emission kinetics are largely lacking, in particular, methodologies that can provide in-depth understanding of polymer/additive interactions. Here, we report on a novel approach using quartz crystal microbalance (QCM) to measure emissions of additives to water from polymer films spin-coated on quartz crystals. The methodology, being accurate and reproducible with a standard error of +/- 2.4%, was applied to a range of organophosphate esters (OPEs) and polymers with varying physicochemical properties. The release of most OPEs reached an apparent steady-state within 10 h. The release curves for the studied OPEs could be fitted using a Weibull model, which shows that the release is a two-phase process with an initial fast phase driven by partitioning of OPEs readily available at or close to the polymer film surface, and a slower phase dominated by diffusion in the polymer. The kinetics of the first emission phase was mainly correlated with the hydrophobicity of the OPEs, whereas the diffusion phase was weakly correlated with molecular size. The developed QCM-based method for assessing and studying release of organic chemicals from a polymeric matrix is well suited for rapid screening of additives in efforts to identify more sustainable replacement polymer additives with lower emission potential.
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| 7. |
- Yin, Ge, et al.
(författare)
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Spatial distribution and bioaccumulation of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in snails (Bellamya aeruginosa) and sediments from Taihu Lake area, China
- 2017
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Ingår i: Environmental Science and Pollution Research. - : SPRINGER HEIDELBERG. - 0944-1344 .- 1614-7499. ; 24:8, s. 7740-7751
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Tidskriftsartikel (refereegranskat)abstract
- Taihu Lake area is one of the densest metropolitan areas in the world including diverse industrial activity. In the present study, the snail (Bellamya aeruginosa) and sediment were collected from the Taihu Lake area to investigate the contamination status, congener pattern, spatial distribution, and bioaccumulation effect of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). The samples underwent liquid extraction, lipid removal by sulfuric acid, and acidic silica gel column, and subsequently analyzed by gas chromatography-electron capture detector (GC-ECD) and gas chromatography-mass spectrometry (GC-MS). Concentration of S22PCBs ranged between 90 and 680 ng g(-1) lipid weight in the snails and between 0.018 and 0.82 ng g(-1) dry weight in the sediments. Concentration of S24PBDEs varied from 25 to 200 ng g(-1) lipid weight in the snails and from 0.62 to 67 ng g(-1) dry weight in the sediments. The levels of PCBs and PBDEs observed were in the medium to low range compared with other studies in the world. CB-153 was the predominant PCB congener in both snails and sediments whereas BDE-209 showed a low bioavailability in the snails, even if it contributed up to 70% of S24PBDEs in the sediments. The spatial distribution showed that the highest concentration of PCBs and PBDEs were detected in samples from Zhushan Lake. East Taihu Lake and Dianshan Lake showed lower concentration of PCBs and PBDEs than the other sampling sites. Biota-sediment accumulation was found between snails and sediments of most of PCB and PBDE congeners except for the highly brominated BDEs (i.e., BDE-209). Therefore, sediment is suggested to be an appropriate matrix to monitor BDE-209 while aquatic species such as the snail could be good for monitoring of PCBs and lower brominated BDE congeners. No significant correlation (Spearman correlation test, two-tailed) of CB-153 (r = 0.54, p = 0.27) or BDE-47 (r = 0.60, p = 0.21) was found between snails and sediments.
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| 8. |
- Zheng, Ziye, et al.
(författare)
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Combining in Silico Tools with Multicriteria Analysis for Alternatives Assessment of Hazardous Chemicals: A Case Study of Decabromodiphenyl Ether Alternatives
- 2019
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Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 53:11, s. 6341-6351
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Tidskriftsartikel (refereegranskat)abstract
- Alternatives assessment is applied for minimizing the risk of unintentionally replacing a hazardous chemical with another hazardous chemical. Central challenges are the diversity of properties to consider and the lack of high-quality experimental data. To address this, a novel alternatives assessment procedure was developed based on in silico data and multicriteria decision analysis (MCDA) methods. As a case study, 16 alternatives to the flame retardant decabromodiphenyl ether were considered. The hazard properties included persistence (P), bioaccumulation potential (B), toxicities (T), and mobility in water (M). Databases were consulted and 2866 experimental data points were collected for the target chemicals; however, these were mostly replicate data points for some hazard criteria for a subset of alternatives. Therefore, in silico data and three MCDA strategies were tested including heat mapping, multiattribute utility theory (MAUT), and Elimination Et Choix Traduisant la REalité (ELECTRE III). The heat map clearly showed that none of the target chemicals are hazard-free, whereas MAUT and ELECTRE III agreed on ranking the "least worst" choices. This study identified several challenges and the complexity in the alternatives assessment processes motivating more case studies combining in silico and MCDA approaches.
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| 9. |
- Zheng, Ziye, et al.
(författare)
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Combining in Silico Tools with Multicriteria Analysis for Alternatives Assessment of Hazardous Chemicals: Accounting for the Transformation Products of decaBDE and Its Alternatives
- 2021
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 1520-5851 .- 0013-936X. ; 55:2, s. 1088-1098
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Tidskriftsartikel (refereegranskat)abstract
- Transformation products ought to be an important consideration in chemical alternatives assessment. In this study, a recently established hazard ranking tool for alternatives assessment based on in silico data and multicriteria decision analysis (MCDA) methods was further developed to include chemical transformation products. Decabromodiphenyl ether (decaBDE) and five proposed alternatives were selected as case chemicals; biotic and abiotic transformation reactions were considered using five in silico tools. A workflow was developed to select transformation products with the highest occurrence potential. The most probable transformation products of the alternative chemicals were often similarly persistent but more mobile in aquatic environments, which implies an increasing exposure potential. When persistence (P), bioaccumulation (B), mobility in the aquatic environment (M), and toxicity (T) are considered (via PBT, PMT, or PBMT composite scoring), all six flame retardants have at least one transformation product that can be considered more hazardous, across diverse MCDA. Even when considering transformation products, the considered alternatives remain less hazardous than decaBDE, though the range of hazard of the five alternatives was reduced. The least hazardous of the considered alternatives were melamine and bis(2-ethylhexyl)-tetrabromophthalate. This developed tool could be integrated within holistic alternatives assessments considering use and life cycle impacts or additionally prioritizing transformation products within (bio)monitoring screening studies.
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| 10. |
- Zheng, Ziye, 1992-
(författare)
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Improving alternatives assessment of plastic additives : exploring in silico tools to identify less hazardous flame retardants
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Alternatives assessment is applied for replacing hazardous chemicals with viable, safer substitutes. High quality experimental hazard data, however, are usually unavailable for this purpose, and obtaining in silico data is the only approach to fill in data gaps. In silico tools also have the advantage of providing a large amount of data with much lower cost and time requirements.The aim of this PhD project was to explore the use of in silico tools for alternatives assessment, and develop practical tools for alternatives assessment of organic plastic additives. For this purpose, flame retardants were used as case chemicals. The major results were:1. Quantitative structure-activity relationship (QSAR) models for endocrine disruption were developed and explored (Paper I and II). These developed models were able to identify chemical properties that impact the binding affinities of brominated organic chemicals with estrogen-related receptor γ (Paper I), and to predict the androgen receptor activity of several organic chemicals, including flame retardants (Paper II);2. A hazard ranking tool was developed for alternatives assessment based on the hazard properties of persistence (P), bioaccumulation (B), mobility in the aquatic environment (M) and toxicity (T). The flame retardant decabromodiphenyl ether (decaBDE) and 16 of its alternatives were taken as case chemicals to develop the tool. From a comparison of experimental and in silico data for these case chemicals, hazard data predicted by in silico tools were identified as the more suitable data source for the hazard ranking tool as the experimental data were confounded by large data gaps (Paper III);3. The inclusion of chemical transformation products for the hazard ranking tool were studied with the case of decaBDE and its alternatives. Several in silico tools were used to predict transformation products, and a strategy for prioritizing chemical transformations with high occurrence potential in the environment was developed (Paper IV);4. Multicriteria decision analysis (MCDA) tools were used to evaluate diverse P, B, M and T endpoints of parent compounds (Paper III) and their transformation products (Paper IV) simultaneously based on in silico data. Three different MCDA methods were explored, and one of them was developed to include the consideration of uncertainties of in silico data;5. In the studied case of decaBDE alternatives, the three different MCDA methods generally agreed on the most and least hazardous alternatives. With the consideration of hazard for the studied flame retardants and their in silico predicted transformation products, two alternatives, melamine and bis(2-ethylhexyl) tetrabromophthalate, were identified as the least hazardous of considered alternatives for decaBDE (Paper III and IV);6. It is critical for the exposure aspect of alternatives assessment to identify the key properties that influence the emission process. For this, a fast measuring method for the emission of polymer additives was developed based on a Quartz Crystal Microbalance (QCM). Empirical linear models were applied to describe the emission patterns (Weibull model) to better understand the chemical mechanism behind the emissions of organophosphate flame retardants from various polymers. The results showed that the octanol-water partitioning coefficient and molecular size are key parameters for the emission process, but also showed that the emission process is complex and is likely driven by a combination of both polymer and additive properties, as well as their interactions (Paper V).This research shows how alternatives assessment can make more effective use of in silico tools. and it also highlights current challenges in the use of these in silico tools that require further development. The next steps to make a holistic alternatives assessment would include an exposure assessment procedure based on the work in Paper V, and combining this with the hazard ranking tools (developed in Paper III and IV), including information on technical feasibilities, economic feasibilities, and also life cycle impacts. The MCDA methods for hazard ranking in Paper III and IV can be further adapted for the decision component of such a more complete alternatives assessment for specific uses of chemicals.
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