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Article ; Online: Systematic Evaluation of the Application of Zebrafish in Toxicology (SEAZIT): Developing a Data Analysis Pipeline for the Assessment of Developmental Toxicity with an Interlaboratory Study.

Hsieh, Jui-Hua / Nolte, Sue / Hamm, Jon T / Wang, Zicong / Roberts, Georgia K / Schmitt, Charles P / Ryan, Kristen R

2023 Volume 11, Issue 5

Abstract: The embryonic zebrafish is a useful vertebrate model for assessing the effects of substances on growth and development. However, cross-laboratory developmental toxicity outcomes can vary and reported developmental defects in zebrafish may not be directly ...

Abstract	The embryonic zebrafish is a useful vertebrate model for assessing the effects of substances on growth and development. However, cross-laboratory developmental toxicity outcomes can vary and reported developmental defects in zebrafish may not be directly comparable between laboratories. To address these limitations for gaining broader adoption of the zebrafish model for toxicological screening, we established the Systematic Evaluation of the Application of Zebrafish in Toxicology (SEAZIT) program to investigate how experimental protocol differences can influence chemical-mediated effects on developmental toxicity (i.e., mortality and the incidence of altered phenotypes). As part of SEAZIT, three laboratories were provided a common and blinded dataset (42 substances) to evaluate substance-mediated effects on developmental toxicity in the embryonic zebrafish model. To facilitate cross-laboratory comparisons, all the raw experimental data were collected, stored in a relational database, and analyzed with a uniform data analysis pipeline. Due to variances in laboratory-specific terminology for altered phenotypes, we utilized ontology terms available from the Ontology Lookup Service (OLS) for Zebrafish Phenotype to enable additional cross-laboratory comparisons. In this manuscript, we utilized data from the first phase of screening (dose range finding, DRF) to highlight the methodology associated with the development of the database and data analysis pipeline, as well as zebrafish phenotype ontology mapping.
Language	English
Publishing date	2023-04-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2733883-6
ISSN	2305-6304 ; 2305-6304
ISSN (online)	2305-6304
ISSN	2305-6304
DOI	10.3390/toxics11050407
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Interlaboratory Study on Zebrafish in Toxicology: Systematic Evaluation of the Application of Zebrafish in Toxicology's (SEAZIT's) Evaluation of Developmental Toxicity.

Hamm, Jon T / Hsieh, Jui-Hua / Roberts, Georgia K / Collins, Bradley / Gorospe, Jenni / Sparrow, Barney / Walker, Nigel J / Truong, Lisa / Tanguay, Robyn L / Dyballa, Sylvia / Miñana, Rafael / Schiavone, Valentina / Terriente, Javier / Weiner, Andrea / Muriana, Arantza / Quevedo, Celia / Ryan, Kristen R

Toxics

2024 Volume 12, Issue 1

Abstract: Embryonic zebrafish represent a useful test system to screen substances for their ability to perturb development. The exposure scenarios, endpoints captured, and data analysis vary among the laboratories who conduct screening. A lack of harmonization ... ...

Abstract	Embryonic zebrafish represent a useful test system to screen substances for their ability to perturb development. The exposure scenarios, endpoints captured, and data analysis vary among the laboratories who conduct screening. A lack of harmonization impedes the comparison of the substance potency and toxicity outcomes across laboratories and may hinder the broader adoption of this model for regulatory use. The Systematic Evaluation of the Application of Zebrafish in Toxicology (SEAZIT) initiative was developed to investigate the sources of variability in toxicity testing. This initiative involved an interlaboratory study to determine whether experimental parameters altered the developmental toxicity of a set of 42 substances (3 tested in duplicate) in three diverse laboratories. An initial dose-range-finding study using in-house protocols was followed by a definitive study using four experimental conditions: chorion-on and chorion-off using both static and static renewal exposures. We observed reasonable agreement across the three laboratories as 33 of 42 test substances (78.6%) had the same activity call. However, the differences in potency seen using variable in-house protocols emphasizes the importance of harmonization of the exposure variables under evaluation in the second phase of this study. The outcome of the Def will facilitate future practical discussions on harmonization within the zebrafish research community.
Language	English
Publishing date	2024-01-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2733883-6
ISSN	2305-6304 ; 2305-6304
ISSN (online)	2305-6304
ISSN	2305-6304
DOI	10.3390/toxics12010093
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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
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Article ; Online: Natural mineral fibers: conducting inhalation toxicology studies-part B: development of a nose-only exposure system for repeat-exposure

Wang, Anbo / Gupta, Amit / Grimm, Michael D / Pressburger, David T / Sparrow, Barney R / Richey, Jamie S / Shaw, John R / Elsass, Karen E / Roberts, Georgia K / Yao, Pei-Li / Stout, Matthew D / Ellis, Benjamin J / Ray, Robyn L

Inhalation toxicology

2023 Volume 35, Issue 7-8, Page(s) 214–229

Abstract: Background: Exposure to asbestos is associated with malignant and nonmalignant respiratory disease. To strengthen the scientific basis for risk assessment on fibers, the National Institute of Environmental Health Sciences (NIEHS) has initiated a series ... ...

Abstract	Background: Exposure to asbestos is associated with malignant and nonmalignant respiratory disease. To strengthen the scientific basis for risk assessment on fibers, the National Institute of Environmental Health Sciences (NIEHS) has initiated a series of studies to address fundamental questions on the toxicology of naturally occurring asbestos and related mineral fibers after inhalation exposure. A prototype nose-only exposure system was previously developed and validated. The prototype system was expanded to a large-scale exposure system in this study for conducting subsequent Results: The exposure system consisting of six exposure carousels was able to independently deliver stable LA 2007 aerosol to individual carousels at target concentrations of 0 (control group), 0.1, 0.3, 1, 3, or 10 mg/m Conclusion: The exposure system developed is ready for use in conducting nose-only inhalation toxicity studies of LA 2007 in rats. The exposure system is anticipated to have applicability for the inhalation toxicity evaluation of other natural mineral fibers of concern.
MeSH term(s)	Rats ; Animals ; Asbestos, Amphibole/toxicity ; Mineral Fibers ; Asbestos ; Aerosols ; Inhalation Exposure/adverse effects
Chemical Substances	Asbestos, Amphibole ; Mineral Fibers ; Asbestos (1332-21-4) ; Aerosols
Language	English
Publishing date	2023-06-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	1038809-6
ISSN	1091-7691 ; 0895-8378
ISSN (online)	1091-7691
ISSN	0895-8378
DOI	10.1080/08958378.2023.2220735
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Article ; Online: Natural mineral fibers: conducting inhalation toxicology studies - part A: Libby Amphibole aerosol generation and characterization method development.

Inhalation toxicology

2023 Volume 35, Issue 7-8, Page(s) 201–213

Abstract: Background: Asbestos has been classified as a human carcinogen, and exposure may increase the risk of diseases associated with impaired respiratory function. As the range of health effects and airborne concentrations that result in health effects across ...

Abstract	Background: Asbestos has been classified as a human carcinogen, and exposure may increase the risk of diseases associated with impaired respiratory function. As the range of health effects and airborne concentrations that result in health effects across asbestos-related natural mineral fiber types are not fully understood, the National Institute of Environmental Health Sciences has established a series of research studies to characterize hazards of natural mineral fibers after inhalation exposure. This paper presents the method development work of this research project. Results: A prototype nose-only exposure system was fabricated to explore the feasibility of generating natural mineral fiber aerosol for Conclusions: Characterization of the prototype system demonstrated feasibility of generating LA 2007 fiber aerosols appropriate for
MeSH term(s)	Humans ; Rats ; Animals ; Asbestos, Amphibole/toxicity ; Mineral Fibers ; Asbestos/analysis ; Carcinogens/toxicity ; Aerosols
Chemical Substances	Asbestos, Amphibole ; Mineral Fibers ; Asbestos (1332-21-4) ; Carcinogens ; Aerosols
Language	English
Publishing date	2023-06-21
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	1038809-6
ISSN	1091-7691 ; 0895-8378
ISSN (online)	1091-7691
ISSN	0895-8378
DOI	10.1080/08958378.2023.2220737
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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 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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Article ; Online: Corrigendum to "Systemic exposure and urinary excretion of vanadium following perinatal subchronic exposure to vanadyl sulfate and sodium metavanadate via drinking water" [Toxicol. Lett. 360 (2022) 53-61].

Waidyanatha, Suramya / Weber, Frank X / Fallacara, Dawn M / Harrington, James M / Levine, Keith / Robinson, Veronica G / Sparrow, Barney R / Stout, Matthew D / Fernando, Reshan / Hooth, Michelle J / Xie, Guanhua / Roberts, Georgia K

Toxicology letters

2022 Volume 373, Page(s) 210

Language	English
Publishing date	2022-11-24
Publishing country	Netherlands
Document type	Published Erratum
ZDB-ID	433788-8
ISSN	1879-3169 ; 0378-4274
ISSN (online)	1879-3169
ISSN	0378-4274
DOI	10.1016/j.toxlet.2022.11.008
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Article ; Online: Systemic exposure and urinary excretion of vanadium following perinatal subchronic exposure to vanadyl sulfate and sodium metavanadate via drinking water.

Toxicology letters

2022 Volume 360, Page(s) 53–61

Abstract: Vanadium is a ubiquitous environmental contaminant although there are limited data to assess potential adverse human health impact following oral exposure. In support of studies investigating the subchronic toxicity of vanadyl sulfate ( ... ...

Abstract	Vanadium is a ubiquitous environmental contaminant although there are limited data to assess potential adverse human health impact following oral exposure. In support of studies investigating the subchronic toxicity of vanadyl sulfate (V
MeSH term(s)	Animals ; Drinking Water ; Female ; Male ; Rats ; Sodium ; Vanadates/toxicity ; Vanadium/toxicity ; Vanadium/urine ; Vanadium Compounds
Chemical Substances	Drinking Water ; Vanadium Compounds ; Vanadium (00J9J9XKDE) ; Vanadates (3WHH0066W5) ; vanadyl sulfate (6DU9Y533FA) ; Sodium (9NEZ333N27)
Language	English
Publishing date	2022-03-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	433788-8
ISSN	1879-3169 ; 0378-4274
ISSN (online)	1879-3169
ISSN	0378-4274
DOI	10.1016/j.toxlet.2022.03.004
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Article ; Online: Comparative inhalation toxicity of ethyltoluene isomers in rats and mice.

Roberts, Georgia K / Willson, Cynthia J / Olivera, Dorian S / Malarkey, David E / Morgan, Daniel L

Inhalation toxicology

2018 Volume 29, Issue 12-14, Page(s) 577–585

Abstract: The C9 alkylbenzenes, composed mostly of ethyltoluenes and trimethylbenzenes, comprise 75-90% of the naphtha fraction of crude oil. Occupational and environmental exposure to C9 alkylbenzenes occur via inhalation. We conducted short-term inhalation ... ...

Abstract	The C9 alkylbenzenes, composed mostly of ethyltoluenes and trimethylbenzenes, comprise 75-90% of the naphtha fraction of crude oil. Occupational and environmental exposure to C9 alkylbenzenes occur via inhalation. We conducted short-term inhalation studies on the ethyltoluene isomers (2-, 3- or 4-) to select one isomer for more comprehensive studies. Male Hsd:Sprague Dawley rats and female B6C3F1/N mice (n = 10) were exposed by nose-only inhalation to 2-, 3- or 4-ethyltoluene (0, 1000 or 2000 ppm) or cumene (a reference compound: 0, 500 or 1000 ppm) 3 h/day, 5 days/week, for 2 weeks. Clinical observations included abnormal gait and delayed righting reflex. Rats and mice exposed to 2000 ppm 2-ethyltoluene and mice exposed to 2000 ppm 4-ethyltoluene were euthanized early in moribund condition; no exposure-related deaths were observed with 3-ethyltoluene or cumene. Histopathology of selected tissues revealed that the nose and liver (rats and mice) and lung (mice only) to be toxicity targets. In the mouse lung, all compounds except 4-ethyltoluene produced bronchial and bronchiolar hyperplasia. In rats and mice, 2-ethyltoluene was the only compound to produce lesions in the nose and liver: in mice, squamous metaplasia and neutrophilic inflammation of the respiratory epithelium and atrophy and degeneration of the olfactory epithelium were observed in the nose and centrilobular hypertrophy and necrosis were observed in the liver. In rats, 2-ethyltoluene exposure produced atrophy of the olfactory epithelium in the nose and centrilobular necrosis in the liver. Based on mortality, body weight effects and histopathology, the 2-ethyltoluene isomer was the most potent isomer.
MeSH term(s)	Animals ; Female ; Inhalation Exposure/adverse effects ; Liver/drug effects ; Liver/pathology ; Lung/drug effects ; Lung/pathology ; Male ; Mice ; Rats ; Rats, Sprague-Dawley ; Respiratory Mucosa/drug effects ; Respiratory Mucosa/pathology ; Stereoisomerism ; Toluene/administration & dosage ; Toluene/analogs & derivatives ; Toluene/toxicity
Chemical Substances	Toluene (3FPU23BG52) ; 3-ethyltoluene (737PTD7O7E)
Language	English
Publishing date	2018-01-29
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1038809-6
ISSN	1091-7691 ; 0895-8378
ISSN (online)	1091-7691
ISSN	0895-8378
DOI	10.1080/08958378.2018.1430190
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Article ; Online: Corrigendum to "Internal dose of vanadium in rats following repeated exposure to vanadyl sulfate and sodium orthovanadate via drinking water" [Toxicology and Applied Pharmacology 412 (2021) 115395].

Harrington, James M / Haines, Laura G / Levine, Keith E / Liyanapatirana, Chamindu / Essader, Amal S / Fernando, Reshan A / Robinson, Veronica G / Roberts, Georgia K / Stout, Matthew D / Hooth, Michelle J / Waidyanatha, Suramya

Toxicology and applied pharmacology

2021 Volume 423, Page(s) 115546

Language	English
Publishing date	2021-04-24
Publishing country	United States
Document type	Published Erratum
ZDB-ID	204477-8
ISSN	1096-0333 ; 0041-008X
ISSN (online)	1096-0333
ISSN	0041-008X
DOI	10.1016/j.taap.2021.115546
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