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Article ; Online: Disposition and metabolism of ethylene glycol 2-ethylhexyl ether in Sprague Dawley rats, B6C3F1/N mice, and

Watson, AtLee T D / Moeller, Benjamin C / Doyle-Eisele, Melanie / Garner, Edwin / Blystone, Chad R / McDonald, Jacob D / Waidyanatha, Suramya

Xenobiotica; the fate of foreign compounds in biological systems

2021 Volume 51, Issue 6, Page(s) 689–702

Abstract: Ethylene glycol 2-ethylhexyl ether (EGEHE) is a solvent used in a variety of applications.We report disposition and metabolism of EGEHE following a single gavage or dermal administration of 50, 150 or 500 mg/kg [ ...

Abstract	Ethylene glycol 2-ethylhexyl ether (EGEHE) is a solvent used in a variety of applications.We report disposition and metabolism of EGEHE following a single gavage or dermal administration of 50, 150 or 500 mg/kg [
MeSH term(s)	Administration, Oral ; Animals ; Ethers ; Ethylene Glycols ; Female ; Hepatocytes ; Male ; Mice ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution
Chemical Substances	Ethers ; Ethylene Glycols
Language	English
Publishing date	2021-03-26
Publishing country	England
Document type	Journal Article
ZDB-ID	120287-x
ISSN	1366-5928 ; 0049-8254
ISSN (online)	1366-5928
ISSN	0049-8254
DOI	10.1080/00498254.2021.1898062
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Article ; Online: Disposition and metabolism of sulfolane in Harlan Sprague Dawley rats and B6C3F1/N mice and in vitro in hepatocytes from rats, mice, and humans.

Waidyanatha, Suramya / Black, Sherry R / Blystone, Chad R / Patel, Purvi R / Watson, Scott L / Snyder, Rodney W / Fennell, Timothy R

Xenobiotica; the fate of foreign compounds in biological systems

2019 Volume 50, Issue 4, Page(s) 442–453

Abstract: Sulfolane has been found as a ground water contaminant near refining sites. These studies investigated ... ...

Abstract	Sulfolane has been found as a ground water contaminant near refining sites. These studies investigated the
MeSH term(s)	Administration, Oral ; Animals ; Female ; Hepatocytes/metabolism ; Humans ; Liver/metabolism ; Male ; Mice ; Mice, Inbred Strains ; Rats ; Rats, Sprague-Dawley ; Thiophenes/metabolism ; Water Pollutants, Chemical/metabolism
Chemical Substances	Thiophenes ; Water Pollutants, Chemical ; sulfolane (Y5L06AH4G5)
Language	English
Publishing date	2019-07-05
Publishing country	England
Document type	Journal Article
ZDB-ID	120287-x
ISSN	1366-5928 ; 0049-8254
ISSN (online)	1366-5928
ISSN	0049-8254
DOI	10.1080/00498254.2019.1630786
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Article ; Online: Immunotoxicity studies of sulfolane following developmental exposure in Hsd:Sprague Dawley SD rats and adult exposure in B6C3F1/N mice.

Watson, AtLee T D / Johnson, Victor J / Luster, Michael I / Burleson, Gary R / Fallacara, Dawn M / Sparrow, Barney R / Cesta, Mark F / Cora, Michelle C / Shockley, Keith R / Stout, Matt D / Blystone, Chad R / Germolec, Dori R

Journal of immunotoxicology

2021 Volume 18, Issue 1, Page(s) 1–12

Abstract: Sulfolane is a solvent used in the petrochemical industry and a groundwater contaminant in areas near refineries. The current studies were conducted to assess the impact of oral exposure to sulfolane on the immune system using two models: (1) a perinatal ...

Abstract	Sulfolane is a solvent used in the petrochemical industry and a groundwater contaminant in areas near refineries. The current studies were conducted to assess the impact of oral exposure to sulfolane on the immune system using two models: (1) a perinatal drinking water exposure to 0, 30, 100, 300, or 1000 mg/L from gestation day (GD) 6 until ∼13 weeks-of-age in Harlan Sprague Dawley rats; and, (2) a 90-day gavage exposure of adult female B6C3F1/N mice to 0, 1, 10, 30, 100, or 300 mg/kg/day. Immune parameters evaluated included measurement of antibody production against sheep red blood cells (SRBC) and keyhole limpet hemocyanin (KLH),
MeSH term(s)	Animals ; Female ; Male ; Mice ; Mice, Inbred Strains ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Sheep ; Spleen ; Thiophenes
Chemical Substances	Thiophenes ; sulfolane (Y5L06AH4G5)
Language	English
Publishing date	2021-08-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	2205064-4
ISSN	1547-6901 ; 1547-691X
ISSN (online)	1547-6901
ISSN	1547-691X
DOI	10.1080/1547691X.2020.1869355
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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
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Article ; Online: Multigenerational reproductive assessment of 4-methylimidazole administered in the diet to Hsd:Sprague Dawley SD rats.

Behl, Mamta / Willson, Cynthia J / Cunny, Helen / Foster, Paul M D / McIntyre, Barry / Shackelford, Cynthia / Shockley, Keith R / McBride, Sandra / Turner, Katie / Waidyanatha, Suramya / Blystone, Chad R

Reproductive toxicology (Elmsford, N.Y.)

2020 Volume 98, Page(s) 13–28

Abstract: The general population, including children and adolescents, is exposed to 4-methylimidazole (4-MI) in the diet. 4-MI is a by-product of caramel color manufacturing. It has been previously classified as a possible human carcinogen and displays potential ... ...

Abstract	The general population, including children and adolescents, is exposed to 4-methylimidazole (4-MI) in the diet. 4-MI is a by-product of caramel color manufacturing. It has been previously classified as a possible human carcinogen and displays potential reproductive toxicity. A follow up assessment of reproductive toxicity was conducted in rats utilizing the reproductive assessment by continuous breeding paradigm, in which multiple generations were exposed to 4-MI in diet at 750, 2500, and 5000 ppm. 4-MI exposure was associated with delays in preputial separation and vaginal opening, impairment in reproductive performance, and concomitant histopathological findings in the prostate, testis, and epididymis at 2500 and 5000 ppm. The Lowest Observed Adverse Effect Level for reproductive (based on prostate atrophy) and developmental toxicity (based on delays in preputial separation and vaginal opening) was 750 ppm, equivalent to approximately 50-60 mg/kg bw/day.
MeSH term(s)	Animals ; Diet ; Epididymis/drug effects ; Epididymis/pathology ; Female ; Imidazoles/toxicity ; Male ; Prostate/drug effects ; Prostate/pathology ; Rats, Sprague-Dawley ; Reproduction/drug effects ; Testis/drug effects ; Testis/pathology ; Vagina/abnormalities ; Vagina/drug effects
Chemical Substances	Imidazoles ; 4-methylimidazole (Q64GF9FV4I)
Language	English
Publishing date	2020-03-27
Publishing country	United States
Document type	Journal Article ; 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.2020.03.005
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Article ; Online: Toxicokinetics of perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) in male and female Hsd:Sprague dawley SD rats following intravenous or gavage administration.

Dzierlenga, Anika L / Robinson, Veronica G / Waidyanatha, Suramya / DeVito, Michael J / Eifrid, Max A / Gibbs, Seth T / Granville, Courtney A / Blystone, Chad R

Xenobiotica; the fate of foreign compounds in biological systems

2019 Volume 50, Issue 6, Page(s) 722–732

Abstract: Poly- and perfluorinated alkyl substances (PFAS) are environmentally persistent chemicals associated with many adverse health outcomes. The National Toxicology Program evaluated the toxicokinetics (TK) of several PFAS to provide context for toxicologic ... ...

Abstract	Poly- and perfluorinated alkyl substances (PFAS) are environmentally persistent chemicals associated with many adverse health outcomes. The National Toxicology Program evaluated the toxicokinetics (TK) of several PFAS to provide context for toxicologic findings.Plasma TK parameters and tissue (liver, kidney, brain) concentrations are reported for perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA) or perfluorodecanoic acid (PFDA) after single-dose administration in male and female Hsd:Sprague-Dawley
MeSH term(s)	Animals ; Caproates/metabolism ; Caproates/toxicity ; Caprylates/metabolism ; Caprylates/toxicity ; Decanoic Acids/metabolism ; Decanoic Acids/toxicity ; Environmental Pollutants/metabolism ; Environmental Pollutants/toxicity ; Female ; Fluorocarbons/metabolism ; Fluorocarbons/toxicity ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Toxicokinetics
Chemical Substances	Caproates ; Caprylates ; Decanoic Acids ; Environmental Pollutants ; Fluorocarbons ; perfluorodecanoic acid (335-76-2) ; perfluorooctanoic acid (947VD76D3L) ; perfluorohexanoic acid (ZP34Q2220R)
Language	English
Publishing date	2019-11-07
Publishing country	England
Document type	Journal Article
ZDB-ID	120287-x
ISSN	1366-5928 ; 0049-8254
ISSN (online)	1366-5928
ISSN	0049-8254
DOI	10.1080/00498254.2019.1683776
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Article ; Online: Toxicokinetics and bioavailability of sulfolane, a ground water contaminant, following oral and intravenous administration in rodents: A dose, species, and sex comparison.

Waidyanatha, Suramya / Black, Sherry R / Fennell, Timothy R / Watson, Scott L / Patel, Purvi R / Cooper, Stephen D / Blake, James / Robinson, Veronica Godfrey / Fernando, Reshan A / Blystone, Chad R

Toxicology and applied pharmacology

2019 Volume 379, Page(s) 114690

Abstract: Sulfolane is a ground water contaminant near refinery sites. The objective of this work was to investigate the toxicokinetics and bioavailability of sulfolane in male and female Harlan Hsd:Sprague Dawley® SD® rats and B6C3F1/N mice following a single ... ...

Abstract	Sulfolane is a ground water contaminant near refinery sites. The objective of this work was to investigate the toxicokinetics and bioavailability of sulfolane in male and female Harlan Hsd:Sprague Dawley® SD® rats and B6C3F1/N mice following a single oral administration of 10, 30, or 100 mg/kg. Sulfolane was rapidly absorbed in rats with the maximum plasma concentration, C
MeSH term(s)	Administration, Intravenous ; Administration, Oral ; Animals ; Biological Availability ; Dose-Response Relationship, Drug ; Female ; Half-Life ; Male ; Mice ; Mice, Inbred Strains ; Rats ; Rats, Sprague-Dawley ; Sex Factors ; Species Specificity ; Thiophenes/administration & dosage ; Thiophenes/pharmacokinetics ; Thiophenes/toxicity
Chemical Substances	Thiophenes ; sulfolane (Y5L06AH4G5)
Language	English
Publishing date	2019-07-22
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	204477-8
ISSN	1096-0333 ; 0041-008X
ISSN (online)	1096-0333
ISSN	0041-008X
DOI	10.1016/j.taap.2019.114690
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Article ; Online: Human and animal evidence of potential transgenerational inheritance of health effects: An evidence map and state-of-the-science evaluation.

Walker, Vickie R / Boyles, Abee L / Pelch, Katherine E / Holmgren, Stephanie D / Shapiro, Andrew J / Blystone, Chad R / Devito, Michael J / Newbold, Retha R / Blain, Robyn / Hartman, Pamela / Thayer, Kristina A / Rooney, Andrew A

Environment international

2018 Volume 115, Page(s) 48–69

Abstract: Background: An increasing number of reports suggest early life exposures result in adverse effects in offspring who were never directly exposed; this phenomenon is termed "transgenerational inheritance." Given concern for public health implications for ... ...

Abstract	Background: An increasing number of reports suggest early life exposures result in adverse effects in offspring who were never directly exposed; this phenomenon is termed "transgenerational inheritance." Given concern for public health implications for potential effects of exposures transmitted to subsequent generations, it is critical to determine how widespread and robust this phenomenon is and to identify the range of exposures and possible outcomes. Objectives: This scoping report examines the evidence for transgenerational inheritance associated with exposure to a wide range of stressors in humans and animals to identify areas of consistency, uncertainty, data gaps, and to evaluate general risk of bias issues for the transgenerational study design. Methods: A protocol was developed to collect and categorize the literature into a systematic evidence map for transgenerational inheritance by health effects, exposures, and evidence streams following the Office of Health Assessment and Translation (OHAT) approach for conducting literature-based health assessments. Results: A PubMed search yielded 63,758 unique records from which 257 relevant studies were identified and categorized into a systematic evidence map by evidence streams (46 human and 211 animal), broad health effect categories, and exposures. Data extracted from the individual studies are available in the Health Assessment Workspace Collaborative (HAWC) program. There are relatively few bodies of evidence where multiple studies evaluated the same exposure and the same or similar outcomes. Studies evaluated for risk of bias generally had multiple issues in design or conduct. Conclusions: The evidence mapping illustrated that risk of bias, few studies, and heterogeneity in exposures and endpoints examined present serious limitations to available bodies of evidence for assessing transgenerational effects. Targeted research is suggested to addressed inconsistencies and risk of bias issues identified, and thereby establish more robust bodies of evidence to critically assess transgenerational effects - particularly by adding data on exposure-outcome pairs where there is some evidence (i.e., reproductive, metabolic, and neurological effects).
MeSH term(s)	Animals ; Biomedical Research/methods ; Biomedical Research/standards ; Databases, Factual ; Environmental Exposure/analysis ; Female ; Humans ; Male ; Maternal Exposure ; Paternal Exposure ; Pregnancy ; Prenatal Exposure Delayed Effects
Language	English
Publishing date	2018-03-14
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2017.12.032
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Zs.A 3131: Show issues

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Article ; Online: Toxicity and carcinogenicity of androstenedione in F344/N rats and B6C3F1 mice.

Blystone, Chad R / Elmore, Susan A / Witt, Kristine L / Malarkey, David E / Foster, Paul M D

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

2011 Volume 49, Issue 9, Page(s) 2116–2124

Abstract: Androstenedione was marketed as a dietary supplement to increase muscle mass during training. Due to concern over long-term use, the NTP evaluated the subchronic and chronic toxicity and carcinogenicity of androstenedione in male and female F344/N rats ... ...

Abstract	Androstenedione was marketed as a dietary supplement to increase muscle mass during training. Due to concern over long-term use, the NTP evaluated the subchronic and chronic toxicity and carcinogenicity of androstenedione in male and female F344/N rats and B6C3F1 mice. In subchronic studies, dose limiting effects were not observed. A chronic (2-year) exposure by gavage at 10, 20, or 50 mg/kg in rats and male mice, and 2, 10, or 50 mg/kg in female mice (50 mg/kg, maximum feasible dose) was conducted. Increased incidences of lung alveolar/bronchiolar adenoma and carcinoma occurred in the 20 mg/kg male rats and increases in mononuclear cell leukemia occurred in the 20 and 50 mg/kg female rats, which may have been related to androstenedione administration. In male and female mice, androstenedione was carcinogenic based upon a significant increase in hepatocellular tumors. A marginal increase in pancreatic islet cell adenomas in male (50 mg/kg) and female (2, 10, 50 mg/kg) mice was considered to be related to androstenedione administration. Interestingly, incidences of male rat Leydig cell adenomas and female rat mammary gland fibroadenomas decreased. In conclusion, androstenedione was determined to be carcinogenic in male and female mice, and may have been carcinogenic in rats.
MeSH term(s)	Androstenedione/toxicity ; Animals ; Carcinogenicity Tests ; Carcinogens/toxicity ; Dose-Response Relationship, Drug ; Female ; Male ; Mice ; Rats ; Rats, Inbred F344
Chemical Substances	Carcinogens ; Androstenedione (409J2J96VR)
Language	English
Publishing date	2011-05-30
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	782617-5
ISSN	1873-6351 ; 0278-6915
ISSN (online)	1873-6351
ISSN	0278-6915
DOI	10.1016/j.fct.2011.05.026
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Article ; Online: Carcinogenicity of perfluorooctanoic acid and perfluorooctanesulfonic acid.

Zahm, Shelia / Bonde, Jens Peter / Chiu, Weihsueh A / Hoppin, Jane / Kanno, Jun / Abdallah, Mohamed / Blystone, Chad R / Calkins, Miriam M / Dong, Guang-Hui / Dorman, David C / Fry, Rebecca / Guo, Huan / Haug, Line S / Hofmann, Jonathan N / Iwasaki, Motoki / Machala, Miroslav / Mancini, Francesca R / Maria-Engler, Silvya S / Møller, Peter /

Ng, Jack C / Pallardy, Marc / Post, Gloria B / Salihovic, Samira / Schlezinger, Jennifer / Soshilov, Anatoly / Steenland, Kyle / Steffensen, Inger-Lise / Tryndyak, Volodymyr / White, Alexandra / Woskie, Susan / Fletcher, Tony / Ahmadi, Ayat / Ahmadi, Nahid / Benbrahim-Tallaa, Lamia / Bijoux, Wendy / Chittiboyina, Shirisha / de Conti, Aline / Facchin, Caterina / Madia, Federica / Mattock, Heidi / Merdas, Mira / Pasqual, Elisa / Suonio, Eero / Viegas, Susana / Zupunski, Ljubica / Wedekind, Roland / Schubauer-Berigan, Mary K

The Lancet. Oncology

2023 Volume 25, Issue 1, Page(s) 16–17

MeSH term(s)	Humans ; Caprylates/toxicity ; Fluorocarbons/toxicity ; Alkanesulfonic Acids/toxicity
Chemical Substances	perfluorooctanoic acid (947VD76D3L) ; perfluorooctane sulfonic acid (9H2MAI21CL) ; Caprylates ; Fluorocarbons ; Alkanesulfonic Acids
Language	English
Publishing date	2023-11-30
Publishing country	England
Document type	Journal Article
ZDB-ID	2049730-1
ISSN	1474-5488 ; 1470-2045
ISSN (online)	1474-5488
ISSN	1470-2045
DOI	10.1016/S1470-2045(23)00622-8
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