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  1. Article ; Online: Short-term toxicity studies of thallium (I) sulfate administered in drinking water to Sprague Dawley rats and B6C3F1/N mice

    Shipkowski, Kelly A. / Hubbard, Troy D. / Ryan, Kristen / Waidyanatha, Suramya / Cunny, Helen / Shockley, Keith R. / Allen, Joshua L. / Toy, Heather / Levine, Keith / Harrington, James / Betz, Laura / Sparrow, Barney / Roberts, Georgia K.

    Toxicology Reports. 2023, v. 10 p.621-632

    2023  

    Abstract: Thallium is a heavy metal that is known to induce a broad spectrum of adverse health effects in humans including alopecia, neurotoxicity, and mortality following high dose acute poisoning events. Widespread human exposure to thallium may occur via ... ...

    Abstract Thallium is a heavy metal that is known to induce a broad spectrum of adverse health effects in humans including alopecia, neurotoxicity, and mortality following high dose acute poisoning events. Widespread human exposure to thallium may occur via consumption of contaminated drinking water; limited toxicity data are available to evaluate the corresponding public health risk. To address this data gap, the Division of Translational Toxicology conducted short-term toxicity studies of a monovalent thallium salt, thallium (I) sulfate. Thallium (I) sulfate was administered via dosed drinking water to time-mated Sprague Dawley (Hsd:Sprague Dawley® SD®) rats (F₀ dams) and their offspring (F₁) from gestation day (GD) 6 until up to postnatal day (PND) 28 at concentrations of 0, 3.13, 6.25, 12.5, 25, or 50 mg/L, and adult male and female B6C3F1/N mice for up to 2 weeks at concentrations of 0, 6.25, 12.5, 25, 50, or 100 mg/L. Rat dams in the 50 mg/L exposure group were removed during gestation, and dams and offspring in the 25 mg/L exposure group were removed on or before PND 0 due to overt toxicity. Exposure to thallium (I) sulfate at concentrations ≤ 12.5 mg/L did not impact F₀ dam body weights, maintenance of pregnancy, littering parameters, or F₁ survival (PND 4–28). However, in F₁ pups, exposure to 12.5 mg/L thallium (I) sulfate resulted in decreased body weight gains relative to control rats and onset of whole-body alopecia. Measurement of thallium concentrations in dam plasma, amniotic fluid, fetuses (GD 18), and pup plasma (PND 4) indicated marked maternal transfer of thallium to offspring during gestation and lactation. Mice exposed to 100 mg/L thallium (I) sulfate were removed early due to overt toxicity, and mice exposed to ≥ 25 mg/L exhibited exposure concentration-related decreases in body weight. Lowest-observed-effect levels of 12.5 mg/L (rats) and 25 mg/L (mice) were determined based on the increased incidence of clinical signs of alopecia in F₁ rat pups and significantly decreased body weights for both rats and mice.
    Keywords adults ; alopecia ; amniotic fluid ; body weight ; females ; heavy metals ; humans ; lactation ; males ; mortality ; neurotoxicity ; pregnancy ; progeny ; public health ; rats ; risk ; sulfates ; thallium ; toxicology ; Thallium (I) sulfate ; Thallium salts ; Dose range-finding study ; Internal concentration assessment
    Language English
    Size p. 621-632.
    Publishing place Elsevier B.V.
    Document type Article ; Online
    Note Use and reproduction
    ZDB-ID 2805786-7
    ISSN 2214-7500
    ISSN 2214-7500
    DOI 10.1016/j.toxrep.2023.05.003
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: Short-term toxicity studies of thallium (I) sulfate administered in drinking water to Sprague Dawley rats and B6C3F1/N mice.

    Shipkowski, Kelly A / Hubbard, Troy D / Ryan, Kristen / Waidyanatha, Suramya / Cunny, Helen / Shockley, Keith R / Allen, Joshua L / Toy, Heather / Levine, Keith / Harrington, James / Betz, Laura / Sparrow, Barney / Roberts, Georgia K

    Toxicology reports

    2023  Volume 10, Page(s) 621–632

    Abstract: Thallium is a heavy metal that is known to induce a broad spectrum of adverse health effects in humans including alopecia, neurotoxicity, and mortality following high dose acute poisoning events. Widespread human exposure to thallium may occur via ... ...

    Abstract Thallium is a heavy metal that is known to induce a broad spectrum of adverse health effects in humans including alopecia, neurotoxicity, and mortality following high dose acute poisoning events. Widespread human exposure to thallium may occur via consumption of contaminated drinking water; limited toxicity data are available to evaluate the corresponding public health risk. To address this data gap, the Division of Translational Toxicology conducted short-term toxicity studies of a monovalent thallium salt, thallium (I) sulfate. Thallium (I) sulfate was administered via dosed drinking water to time-mated Sprague Dawley (Hsd:Sprague Dawley® SD®) rats (F
    Language English
    Publishing date 2023-05-11
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 2805786-7
    ISSN 2214-7500 ; 2214-7500
    ISSN (online) 2214-7500
    ISSN 2214-7500
    DOI 10.1016/j.toxrep.2023.05.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Assessment of Ah receptor transcriptional activity mediated by halogenated dibenzo-p-dioxins and dibenzofurans (PXDD/Fs) in human and mouse cell systems.

    Organtini, Kari L / Hubbard, Troy D / Perdew, Gary H / Dorman, Frank L

    Journal of environmental science and health. Part A, Toxic/hazardous substances & environmental engineering

    2017  Volume 52, Issue 14, Page(s) 1295–1302

    Abstract: Polybrominated and mixed bromo/chloro dibenzo-p-dioxins and dibenzofurans (PXDD/Fs) are emerging environmental contaminants of concern. Thus far, an understanding of the toxicological behavior of these chemical species and their impact upon human health ... ...

    Abstract Polybrominated and mixed bromo/chloro dibenzo-p-dioxins and dibenzofurans (PXDD/Fs) are emerging environmental contaminants of concern. Thus far, an understanding of the toxicological behavior of these chemical species and their impact upon human health is incomplete. Here we utilized human and mouse hepatocellular carcinoma cell lines to examine the ability of differentially halogenated PXDD/F congeners to induce aryl hydrocarbon receptor (AHR)-mediated transcriptional activity. Dose-response experiments in reporter cell lines identified varied potencies among differentially halogenated PXDD/F isomers by comparison of EC
    Language English
    Publishing date 2017-12-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 196584-0
    ISSN 1532-4117 ; 0360-1226 ; 1077-1204 ; 1093-4529
    ISSN (online) 1532-4117
    ISSN 0360-1226 ; 1077-1204 ; 1093-4529
    DOI 10.1080/10934529.2017.1362290
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Indole and Tryptophan Metabolism: Endogenous and Dietary Routes to Ah Receptor Activation.

    Hubbard, Troy D / Murray, Iain A / Perdew, Gary H

    Drug metabolism and disposition: the biological fate of chemicals

    2015  Volume 43, Issue 10, Page(s) 1522–1535

    Abstract: The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor recognized for its role in xenobiotic metabolism. The physiologic function of AHR has expanded to include roles in immune regulation, organogenesis, mucosal barrier function, ... ...

    Abstract The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor recognized for its role in xenobiotic metabolism. The physiologic function of AHR has expanded to include roles in immune regulation, organogenesis, mucosal barrier function, and the cell cycle. These functions are likely dependent upon ligand-mediated activation of the receptor. High-affinity ligands of AHR have been classically defined as xenobiotics, such as polychlorinated biphenyls and dioxins. Identification of endogenous AHR ligands is key to understanding the physiologic functions of this enigmatic receptor. Metabolic pathways targeting the amino acid tryptophan and indole can lead to a myriad of metabolites, some of which are AHR ligands. Many of these ligands exhibit species selective preferential binding to AHR. The discovery of specific tryptophan metabolites as AHR ligands may provide insight concerning where AHR is activated in an organism, such as at the site of inflammation and within the intestinal tract.
    MeSH term(s) Animals ; Dietary Supplements ; Fruit/metabolism ; Gastrointestinal Tract/metabolism ; Humans ; Indoles/metabolism ; Receptors, Aryl Hydrocarbon/metabolism ; Tryptophan/metabolism ; Vegetables/metabolism
    Chemical Substances Indoles ; Receptors, Aryl Hydrocarbon ; indole (8724FJW4M5) ; Tryptophan (8DUH1N11BX)
    Language English
    Publishing date 2015-06-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 186795-7
    ISSN 1521-009X ; 0090-9556
    ISSN (online) 1521-009X
    ISSN 0090-9556
    DOI 10.1124/dmd.115.064246
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: The aryl hydrocarbon receptor activates ceramide biosynthesis in mice contributing to hepatic lipogenesis

    Liu, Qing / Zhang, Limin / Allman, Erik L / Hubbard, Troy D / Murray, Iain A / Hao, Fuhua / Tian, Yuan / Gui, Wei / Nichols, Robert G / Smith, Philip B / Anitha, Mallappa / Perdew, Gary H / Patterson, Andrew D

    Toxicology. 2021 June 30, v. 458

    2021  

    Abstract: Aryl hydrocarbon receptor (AHR) activation via 2,3,7,8-tetrachlorodibenzofuran (TCDF) induces the accumulation of hepatic lipids. Here we report that AHR activation by TCDF (24 μg/kg body weight given orally for five days) induced significant elevation ... ...

    Abstract Aryl hydrocarbon receptor (AHR) activation via 2,3,7,8-tetrachlorodibenzofuran (TCDF) induces the accumulation of hepatic lipids. Here we report that AHR activation by TCDF (24 μg/kg body weight given orally for five days) induced significant elevation of hepatic lipids including ceramides in mice, was associated with increased expression of key ceramide biosynthetic genes, and increased activity of their respective enzymes. Results from chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA) and cell-based reporter luciferase assays indicated that AHR directly activated the serine palmitoyltransferase long chain base subunit 2 (Sptlc2, encodes serine palmitoyltransferase 2 (SPT2)) gene whose product catalyzes the initial rate-limiting step in de novo sphingolipid biosynthesis. Hepatic ceramide accumulation was further confirmed by mass spectrometry-based lipidomics. Taken together, our results revealed that AHR activation results in the up-regulation of Sptlc2, leading to ceramide accumulation, thus promoting lipogenesis, which can induce hepatic lipid accumulation.
    Keywords aryl hydrocarbon receptors ; biosynthesis ; body weight ; ceramides ; chromatin immunoprecipitation ; gel electrophoresis ; genes ; lipidomics ; lipogenesis ; luciferase ; mass spectrometry ; reaction kinetics ; serine C-palmitoyltransferase ; toxicology
    Language English
    Dates of publication 2021-0630
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 184557-3
    ISSN 1879-3185 ; 0300-483X
    ISSN (online) 1879-3185
    ISSN 0300-483X
    DOI 10.1016/j.tox.2021.152831
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: The aryl hydrocarbon receptor activates ceramide biosynthesis in mice contributing to hepatic lipogenesis.

    Liu, Qing / Zhang, Limin / Allman, Erik L / Hubbard, Troy D / Murray, Iain A / Hao, Fuhua / Tian, Yuan / Gui, Wei / Nichols, Robert G / Smith, Philip B / Anitha, Mallappa / Perdew, Gary H / Patterson, Andrew D

    Toxicology

    2021  Volume 458, Page(s) 152831

    Abstract: Aryl hydrocarbon receptor (AHR) activation via 2,3,7,8-tetrachlorodibenzofuran (TCDF) induces the accumulation of hepatic lipids. Here we report that AHR activation by TCDF (24  μg/kg body weight given orally for five days) induced significant elevation ... ...

    Abstract Aryl hydrocarbon receptor (AHR) activation via 2,3,7,8-tetrachlorodibenzofuran (TCDF) induces the accumulation of hepatic lipids. Here we report that AHR activation by TCDF (24  μg/kg body weight given orally for five days) induced significant elevation of hepatic lipids including ceramides in mice, was associated with increased expression of key ceramide biosynthetic genes, and increased activity of their respective enzymes. Results from chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA) and cell-based reporter luciferase assays indicated that AHR directly activated the serine palmitoyltransferase long chain base subunit 2 (Sptlc2, encodes serine palmitoyltransferase 2 (SPT2)) gene whose product catalyzes the initial rate-limiting step in de novo sphingolipid biosynthesis. Hepatic ceramide accumulation was further confirmed by mass spectrometry-based lipidomics. Taken together, our results revealed that AHR activation results in the up-regulation of Sptlc2, leading to ceramide accumulation, thus promoting lipogenesis, which can induce hepatic lipid accumulation.
    MeSH term(s) Activation, Metabolic/drug effects ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Benzofurans/pharmacology ; Ceramides/biosynthesis ; Ceramides/genetics ; Gene Expression Regulation/drug effects ; Humans ; Lipidomics ; Lipogenesis/drug effects ; Liver/drug effects ; Liver/enzymology ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Aryl Hydrocarbon/genetics ; Receptors, Aryl Hydrocarbon/metabolism ; Serine C-Palmitoyltransferase/genetics ; Serine C-Palmitoyltransferase/metabolism ; Sphingomyelin Phosphodiesterase/metabolism ; Triglycerides/metabolism
    Chemical Substances Ahr protein, mouse ; Basic Helix-Loop-Helix Transcription Factors ; Benzofurans ; Ceramides ; Receptors, Aryl Hydrocarbon ; Triglycerides ; Serine C-Palmitoyltransferase (EC 2.3.1.50) ; Sptlc2 protein, mouse (EC 2.3.1.50) ; Sphingomyelin Phosphodiesterase (EC 3.1.4.12) ; 2,3,7,8-tetrachlorodibenzofuran (XZJ41GQI5D)
    Language English
    Publishing date 2021-06-09
    Publishing country Ireland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 184557-3
    ISSN 1879-3185 ; 0300-483X
    ISSN (online) 1879-3185
    ISSN 0300-483X
    DOI 10.1016/j.tox.2021.152831
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Butylparaben multigenerational reproductive assessment by continuous breeding in Hsd:Sprague Dawley SD rats following dietary exposure.

    Hubbard, Troy D / Brix, Amy / Blystone, Chad R / McIntyre, Barry S / Shockley, Keith / Cunny, Helen / Waidyanatha, Suramya / Turner, Katie J / McBride, Sandra / Roberts, Georgia K

    Reproductive toxicology (Elmsford, N.Y.)

    2020  Volume 96, Page(s) 258–272

    Abstract: Butylparaben (BP) is an antimicrobial agent utilized for decades as a preservative in numerous consumer products. The safety of parabens has recently come under scrutiny based on reports of estrogenic activity and suggested adverse effects upon the ... ...

    Abstract Butylparaben (BP) is an antimicrobial agent utilized for decades as a preservative in numerous consumer products. The safety of parabens has recently come under scrutiny based on reports of estrogenic activity and suggested adverse effects upon the reproductive system. Due to the limited availability of studies that address the potential for BP exposure to induce reproductive toxicity, and clear evidence of human exposure, the National Toxicology Program conducted a multigenerational continuous breeding study to evaluate the impact of dietary BP-exposure at 0, 5000, 15,000, or 40,000 ppm on reproductive and developmental parameters in Hsd:Sprague Dawley SD rats. BP-exposure was not associated with adverse alterations of fertility, fecundity, pubertal attainment, or reproductive parameters in F0, F1, or F2 generations. Exposure-dependent increases in liver weights, and incidences of non-neoplastic liver lesions suggest the liver is a target organ of BP toxicity. No findings were observed that would support the purported mechanism of BP-induced endocrine disruption in perinatally-exposed rodents.
    MeSH term(s) Animals ; Anti-Infective Agents/toxicity ; Dietary Exposure ; Female ; Liver/drug effects ; Liver/pathology ; Male ; Maternal-Fetal Exchange ; Parabens/toxicity ; Pregnancy ; Rats, Sprague-Dawley ; Reproduction/drug effects ; Sexual Maturation/drug effects
    Chemical Substances Anti-Infective Agents ; Parabens ; butylparaben (3QPI1U3FV8)
    Language English
    Publishing date 2020-07-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 639342-1
    ISSN 1873-1708 ; 0890-6238
    ISSN (online) 1873-1708
    ISSN 0890-6238
    DOI 10.1016/j.reprotox.2020.07.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Microbiota Metabolism Promotes Synthesis of the Human Ah Receptor Agonist 2,8-Dihydroxyquinoline

    Hubbard, Troy D / Amin, Shantu / Dong, Fangcong / Gowda, Krishne / Lin, Jyh Ming / Liu, Qing / Miller, Charles / Murray, Iain A / Patterson, Andrew D / Perdew, Gary H / Smith, Philip B

    Journal of proteome research. 2019 Feb. 19, v. 18, no. 4

    2019  

    Abstract: The aryl hydrocarbon receptor (AHR) is a major regulator of immune function within the gastrointestinal tract. Resident microbiota are capable of influencing AHR-dependent signaling pathways via production of an array of bioactive molecules that act as ... ...

    Abstract The aryl hydrocarbon receptor (AHR) is a major regulator of immune function within the gastrointestinal tract. Resident microbiota are capable of influencing AHR-dependent signaling pathways via production of an array of bioactive molecules that act as AHR agonists, such as indole or indole-3-aldehyde. Bacteria produce a number of quinoline derivatives, of which some function as quorum-sensing molecules. Thus, we screened relevant hydroxyquinoline derivatives for AHR activity using AHR responsive reporter cell lines. 2,8-Dihydroxyquinoline (2,8-DHQ) was identified as a species-specific AHR agonist that exhibits full AHR agonist activity in human cell lines, but only induces modest AHR activity in mouse cells. Additional dihydroxylated quinolines tested failed to activate the human AHR. Nanomolar concentrations of 2,8-DHQ significantly induced CYP1A1 expression and, upon cotreatment with cytokines, synergistically induced IL6 expression. Ligand binding competition studies subsequently confirmed 2,8-DHQ to be a human AHR ligand. Several dihydroxyquinolines were detected in human fecal samples, with concentrations of 2,8-DHQ ranging between 0 and 3.4 pmol/mg feces. Additionally, in mice the microbiota was necessary for the presence of DHQ in cecal contents. These results suggest that microbiota-derived 2,8-DHQ would contribute to AHR activation in the human gut, and thus participate in the protective and homeostatic effects observed with gastrointestinal AHR activation.
    Keywords agonists ; bacteria ; bioactive compounds ; feces ; gastrointestinal system ; human cell lines ; humans ; immune response ; interleukin-6 ; ligands ; metabolism ; mice ; proteome ; quinoline ; quorum sensing ; signal transduction
    Language English
    Dates of publication 2019-0219
    Size p. 1715-1724.
    Publishing place American Chemical Society
    Document type Article
    ZDB-ID 2078618-9
    ISSN 1535-3907 ; 1535-3893
    ISSN (online) 1535-3907
    ISSN 1535-3893
    DOI 10.1021/acs.jproteome.8b00946
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: Microbiota Metabolism Promotes Synthesis of the Human Ah Receptor Agonist 2,8-Dihydroxyquinoline.

    Hubbard, Troy D / Liu, Qing / Murray, Iain A / Dong, Fangcong / Miller, Charles / Smith, Philip B / Gowda, Krishne / Lin, Jyh Ming / Amin, Shantu / Patterson, Andrew D / Perdew, Gary H

    Journal of proteome research

    2019  Volume 18, Issue 4, Page(s) 1715–1724

    Abstract: The aryl hydrocarbon receptor (AHR) is a major regulator of immune function within the gastrointestinal tract. Resident microbiota are capable of influencing AHR-dependent signaling pathways via production of an array of bioactive molecules that act as ... ...

    Abstract The aryl hydrocarbon receptor (AHR) is a major regulator of immune function within the gastrointestinal tract. Resident microbiota are capable of influencing AHR-dependent signaling pathways via production of an array of bioactive molecules that act as AHR agonists, such as indole or indole-3-aldehyde. Bacteria produce a number of quinoline derivatives, of which some function as quorum-sensing molecules. Thus, we screened relevant hydroxyquinoline derivatives for AHR activity using AHR responsive reporter cell lines. 2,8-Dihydroxyquinoline (2,8-DHQ) was identified as a species-specific AHR agonist that exhibits full AHR agonist activity in human cell lines, but only induces modest AHR activity in mouse cells. Additional dihydroxylated quinolines tested failed to activate the human AHR. Nanomolar concentrations of 2,8-DHQ significantly induced CYP1A1 expression and, upon cotreatment with cytokines, synergistically induced IL6 expression. Ligand binding competition studies subsequently confirmed 2,8-DHQ to be a human AHR ligand. Several dihydroxyquinolines were detected in human fecal samples, with concentrations of 2,8-DHQ ranging between 0 and 3.4 pmol/mg feces. Additionally, in mice the microbiota was necessary for the presence of DHQ in cecal contents. These results suggest that microbiota-derived 2,8-DHQ would contribute to AHR activation in the human gut, and thus participate in the protective and homeostatic effects observed with gastrointestinal AHR activation.
    MeSH term(s) Animals ; Basic Helix-Loop-Helix Transcription Factors/agonists ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Caco-2 Cells ; Feces/microbiology ; Gastrointestinal Microbiome/physiology ; Humans ; Mice ; Oxyquinoline/analogs & derivatives ; Oxyquinoline/metabolism ; Oxyquinoline/pharmacology ; Receptors, Aryl Hydrocarbon/agonists ; Receptors, Aryl Hydrocarbon/genetics ; Receptors, Aryl Hydrocarbon/metabolism ; Tryptophan/metabolism
    Chemical Substances AHR protein, human ; Basic Helix-Loop-Helix Transcription Factors ; Receptors, Aryl Hydrocarbon ; 2,8-dihydroxyquinoline (15450-76-7) ; Oxyquinoline (5UTX5635HP) ; Tryptophan (8DUH1N11BX)
    Language English
    Publishing date 2019-03-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 2078618-9
    ISSN 1535-3907 ; 1535-3893
    ISSN (online) 1535-3907
    ISSN 1535-3893
    DOI 10.1021/acs.jproteome.8b00946
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Using Tox21 High-Throughput Screening Assays for the Evaluation of Botanical and Dietary Supplements.

    Hubbard, Troy D / Hsieh, Jui-Hua / Rider, Cynthia V / Sipes, Nisha S / Sedykh, Alexander / Collins, Bradley J / Auerbach, Scott S / Xia, Menghang / Huang, Ruili / Walker, Nigel J / DeVito, Michael J

    Applied in vitro toxicology

    2019  Volume 5, Issue 1, Page(s) 10–25

    Abstract: Introduction: ...

    Abstract Introduction:
    Language English
    Publishing date 2019-03-09
    Publishing country United States
    Document type Journal Article
    ISSN 2332-1512
    ISSN 2332-1512
    DOI 10.1089/aivt.2018.0020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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