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Book ; Online ; E-Book: Endocrine disruptors, brain, and behavior

Patisaul, Heather B. / Belcher, Scott M.

(Oxford series in behavioral neuroendocrinology)

2017

Author's details	Heather B. Patisaul and Scott M. Belcher
Series title	Oxford series in behavioral neuroendocrinology
Keywords	Endocrine disrupting chemicals/Health aspects ; Endocrine glands/Diseases
Subject code	616.4071
Language	English
Size	1 Online-Ressource (xi, 258 Seiten), Illustrationen
Publisher	Oxford University Press
Publishing place	New York, NY
Publishing country	United States
Document type	Book ; Online ; E-Book
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
HBZ-ID	HT019383009
ISBN	978-0-19-993574-1 ; 9780199935734 ; 0-19-993574-2 ; 0199935734
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Quantitative cross-species comparison of serum albumin binding of per- and polyfluoroalkyl substances from five structural classes.

Starnes, Hannah M / Jackson, Thomas W / Rock, Kylie D / Belcher, Scott M

Toxicological sciences : an official journal of the Society of Toxicology

2024 Volume 199, Issue 1, Page(s) 132–149

Abstract: Per- and polyfluoroalkyl substances (PFAS) are a class of over 8000 chemicals, many of which are persistent, bioaccumulative, and toxic to humans, livestock, and wildlife. Serum protein binding affinity is instrumental in understanding PFAS toxicity, yet ...

Abstract	Per- and polyfluoroalkyl substances (PFAS) are a class of over 8000 chemicals, many of which are persistent, bioaccumulative, and toxic to humans, livestock, and wildlife. Serum protein binding affinity is instrumental in understanding PFAS toxicity, yet experimental binding data is limited to only a few PFAS congeners. Previously, we demonstrated the usefulness of a high-throughput, in vitro differential scanning fluorimetry assay for determination of relative binding affinities of human serum albumin for 24 PFAS congeners from 6 chemical classes. In the current study, we used this assay to comparatively examine differences in human, bovine, porcine, and rat serum albumin binding of 8 structurally informative PFAS congeners from 5 chemical classes. With the exception of the fluorotelomer alcohol 1H, 1H, 2H, 2H-perfluorooctanol (6:2 FTOH), each PFAS congener bound by human serum albumin was also bound by bovine, porcine, and rat serum albumin. The critical role of the charged functional headgroup in albumin binding was supported by the inability of albumin of each species tested to bind 6:2 FTOH. Significant interspecies differences in serum albumin binding affinities were identified for each of the bound PFAS congeners. Relative to human albumin, perfluoroalkyl carboxylic and sulfonic acids were bound with greater affinity by porcine and rat serum albumin, and the perfluoroalkyl ether acid congener bound with lower affinity to porcine and bovine serum albumin. These comparative affinity data for PFAS binding by serum albumin from human, experimental model, and livestock species reduce critical interspecies uncertainty and improve accuracy of predictive bioaccumulation and toxicity assessments for PFAS.
MeSH term(s)	Animals ; Fluorocarbons/chemistry ; Fluorocarbons/toxicity ; Fluorocarbons/metabolism ; Humans ; Species Specificity ; Protein Binding ; Serum Albumin/metabolism ; Serum Albumin/chemistry ; Swine ; Rats ; Cattle ; Serum Albumin, Human/metabolism ; Serum Albumin, Human/chemistry
Chemical Substances	Fluorocarbons ; Serum Albumin ; Serum Albumin, Human (ZIF514RVZR)
Language	English
Publishing date	2024-03-22
Publishing country	United States
Document type	Journal Article ; Comparative Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1420885-4
ISSN	1096-0929 ; 1096-6080
ISSN (online)	1096-0929
ISSN	1096-6080
DOI	10.1093/toxsci/kfae028
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Article: Quantitative Cross-Species Comparison of Serum Albumin Binding of Per- and Polyfluoroalkyl Substances from Five Structural Classes.

Starnes, Hannah M / Jackson, Thomas W / Rock, Kylie D / Belcher, Scott M

bioRxiv : the preprint server for biology

2023

Abstract: Per- and polyfluoroalkyl substances (PFAS) are a class of over 8,000 chemicals that are persistent, bioaccumulative, and toxic to humans, livestock, and wildlife. Serum protein binding affinity is instrumental in understanding PFAS toxicity, yet ... ...

Abstract	Per- and polyfluoroalkyl substances (PFAS) are a class of over 8,000 chemicals that are persistent, bioaccumulative, and toxic to humans, livestock, and wildlife. Serum protein binding affinity is instrumental in understanding PFAS toxicity, yet experimental binding data is limited to only a few PFAS congeners. Previously, we demonstrated the usefulness of a high-throughput,
Language	English
Publishing date	2023-11-14
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.10.566613
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Article ; Online: Gestational Cd Exposure in the CD-1 Mouse Sex-Specifically Disrupts Essential Metal Ion Homeostasis.

Jackson, Thomas W / Baars, Oliver / Belcher, Scott M

Toxicological sciences : an official journal of the Society of Toxicology

2022 Volume 187, Issue 2, Page(s) 254–266

Abstract: In CD-1 mice, gestational-only exposure to cadmium (Cd) causes female-specific hepatic insulin resistance, metabolic disruption, and obesity. To evaluate whether sex differences in uptake and changes in essential metal concentrations contribute to ... ...

Abstract	In CD-1 mice, gestational-only exposure to cadmium (Cd) causes female-specific hepatic insulin resistance, metabolic disruption, and obesity. To evaluate whether sex differences in uptake and changes in essential metal concentrations contribute to metabolic outcomes, placental and liver Cd and essential metal concentrations were quantified in male and female offspring perinatally exposed to 500 ppb CdCl2. Exposure resulted in increased maternal liver Cd+2 concentrations (364 µg/kg) similar to concentrations found in non-occupationally exposed human liver. At gestational day (GD) 18, placental Cd and manganese concentrations were significantly increased in exposed males and females, and zinc was significantly decreased in females. Placental efficiency was significantly decreased in GD18-exposed males. Increases in hepatic Cd concentrations and a transient prenatal increase in zinc were observed in exposed female liver. Fetal and adult liver iron concentrations were decreased in both sexes, and decreases in hepatic zinc, iron, and manganese were observed in exposed females. Analysis of GD18 placental and liver metallothionein mRNA expression revealed significant Cd-induced upregulation of placental metallothionein in both sexes, and a significant decrease in fetal hepatic metallothionein in exposed females. In placenta, expression of metal ion transporters responsible for metal ion uptake was increased in exposed females. In liver of exposed adult female offspring, expression of the divalent cation importer (Slc39a14/Zip14) decreased, whereas expression of the primary exporter (Slc30a10/ZnT10) increased. These findings demonstrate that Cd can preferentially cross the female placenta, accumulate in the liver, and cause lifelong dysregulation of metal ion concentrations associated with metabolic disruption.
MeSH term(s)	Animals ; Cadmium/toxicity ; Cation Transport Proteins/genetics ; Cation Transport Proteins/metabolism ; Female ; Homeostasis ; Iron/metabolism ; Liver/metabolism ; Male ; Manganese/metabolism ; Manganese/toxicity ; Metallothionein/genetics ; Metallothionein/metabolism ; Mice ; Placenta/metabolism ; Pregnancy ; Zinc/toxicity
Chemical Substances	Cation Transport Proteins ; SLC39A14 protein, mouse ; Cadmium (00BH33GNGH) ; Manganese (42Z2K6ZL8P) ; Metallothionein (9038-94-2) ; Iron (E1UOL152H7) ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2022-02-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1420885-4
ISSN	1096-0929 ; 1096-6080
ISSN (online)	1096-0929
ISSN	1096-6080
DOI	10.1093/toxsci/kfac027
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Article ; Online: A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior.

Starnes, Hannah M / Rock, Kylie D / Jackson, Thomas W / Belcher, Scott M

Frontiers in toxicology

2022 Volume 4, Page(s) 881584

Abstract: Per- and polyfluoroalkyl substances (PFAS) are a class of structurally diverse synthetic organic chemicals that are chemically stable, resistant to degradation, and persistent in terrestrial and aquatic environments. Widespread use of PFAS in industrial ... ...

Abstract	Per- and polyfluoroalkyl substances (PFAS) are a class of structurally diverse synthetic organic chemicals that are chemically stable, resistant to degradation, and persistent in terrestrial and aquatic environments. Widespread use of PFAS in industrial processing and manufacturing over the last 70 years has led to global contamination of built and natural environments. The brain is a lipid rich and highly vascularized organ composed of long-lived neurons and glial cells that are especially vulnerable to the impacts of persistent and lipophilic toxicants. Generally, PFAS partition to protein-rich tissues of the body, primarily the liver and blood, but are also detected in the brains of humans, wildlife, and laboratory animals. Here we review factors impacting the absorption, distribution, and accumulation of PFAS in the brain, and currently available evidence for neurotoxic impacts defined by disruption of neurochemical, neurophysiological, and behavioral endpoints. Emphasis is placed on the neurotoxic potential of exposures during critical periods of development and in sensitive populations, and factors that may exacerbate neurotoxicity of PFAS. While limitations and inconsistencies across studies exist, the available body of evidence suggests that the neurobehavioral impacts of long-chain PFAS exposures during development are more pronounced than impacts resulting from exposure during adulthood. There is a paucity of experimental studies evaluating neurobehavioral and molecular mechanisms of short-chain PFAS, and even greater data gaps in the analysis of neurotoxicity for PFAS outside of the perfluoroalkyl acids. Whereas most experimental studies were focused on acute and subchronic impacts resulting from high dose exposures to a single PFAS congener, more realistic exposures for humans and wildlife are mixtures exposures that are relatively chronic and low dose in nature. Our evaluation of the available human epidemiological, experimental, and wildlife data also indicates heightened accumulation of perfluoroalkyl acids in the brain after environmental exposure, in comparison to the experimental studies. These findings highlight the need for additional experimental analysis of neurodevelopmental impacts of environmentally relevant concentrations and complex mixtures of PFAS.
Language	English
Publishing date	2022-04-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	2673-3080
ISSN (online)	2673-3080
DOI	10.3389/ftox.2022.881584
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Article ; Online: Response to the Letter by Gallo D., et al.

Belcher, Scott M

Endocrinology

2015 Volume 156, Issue 8, Page(s) L8–9

MeSH term(s)	Animals ; Apoptosis/genetics ; Estrogen Receptor beta/genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Male ; Medulloblastoma/genetics ; RNA, Messenger/metabolism ; Receptor, IGF Type 1/genetics
Chemical Substances	Estrogen Receptor beta ; RNA, Messenger ; Receptor, IGF Type 1 (EC 2.7.10.1)
Language	English
Publishing date	2015-08
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/en.2015-1484
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Article ; Online: Comparative assessment of blood mercury in American alligators (Alligator mississippiensis) from Coastal North Carolina and Florida.

Belcher, Scott M / Guillette, Matthew P / Robb, Frank / Rock, Kylie D

Ecotoxicology (London, England)

2022 Volume 31, Issue 7, Page(s) 1137–1146

Abstract: Mercury (Hg) is a widespread and harmful persistent pollutant of aquatic ecosystems. Except for the northern most populations of American alligators (Alligator Mississippiensis) found in North Carolina, the potential adverse health impacts of Hg on ... ...

Abstract	Mercury (Hg) is a widespread and harmful persistent pollutant of aquatic ecosystems. Except for the northern most populations of American alligators (Alligator Mississippiensis) found in North Carolina, the potential adverse health impacts of Hg on ecosystems and humans consuming alligator meat have been studied for over three decades. Now that alligators are being recreationally hunted and consumed across their range, it is especially important to monitor toxic contaminant levels to best understand possible adverse impacts of exposures on alligator populations and human health. In this study, we determined blood Hg concentrations in American alligators from an urbanized site in Wilmington, NC, a nearby site at Lake Waccamaw, NC, and a site on the St Johns River in Florida. Median blood total Hg (tHg) concentrations were particularly high at Lake Waccamaw (526 ng/g, range 152-946 ng/g), resulting in median muscle concentrations (0.48 mg/kg, range 0.13-0.88 mg/kg) well above US EPA screening values for fish consumption. Median concentrations at the Wilmington site (69 ng/g, range 22-336 ng/g) were generally low, and Hg concentrations from the St Johns River site (143 ng/g, range 54-244 ng/g) were comparable to those reported in previous studies. Analysis of relationships between tHg concentrations and a panel of blood chemistry biomarkers found only modest concentration-dependent impact on biomarkers of renal function. The results of this study reveal that local environmental factors greatly impact Hg bioaccumulation in alligators, findings that reaffirm local contaminant biomonitoring in alligator populations will be critical for affective management and determination of guidelines for safe consumption of harvested alligators.
MeSH term(s)	Alligators and Crocodiles ; Animals ; Ecosystem ; Environmental Monitoring ; Florida ; Humans ; Mercury/analysis ; North Carolina
Chemical Substances	Mercury (FXS1BY2PGL)
Language	English
Publishing date	2022-08-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	34042-x
ISSN	1573-3017 ; 0963-9292
ISSN (online)	1573-3017
ISSN	0963-9292
DOI	10.1007/s10646-022-02573-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Editorial overview: Endocrine and metabolic diseases: conversations on endocrine disruptors - rising above the din.

Belcher, Scott M

Current opinion in pharmacology

2014 Volume 19, Page(s) vi–vii

MeSH term(s)	Endocrine Disruptors/toxicity ; Endocrine System Diseases ; Environmental Exposure/adverse effects ; Environmental Pollutants/toxicity ; Humans ; Metabolic Diseases ; Risk Assessment
Chemical Substances	Endocrine Disruptors ; Environmental Pollutants
Language	English
Publishing date	2014-12
Publishing country	England
Document type	Editorial
ZDB-ID	2037057-X
ISSN	1471-4973 ; 1471-4892
ISSN (online)	1471-4973
ISSN	1471-4892
DOI	10.1016/j.coph.2014.10.003
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Zs.A 5608: Show issues

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Article: Comparative assessment of blood mercury in American alligators (Alligator mississippiensis) from Coastal North Carolina and Florida

Belcher, Scott M. / Guillette, Matthew P. / Robb, Frank / Rock, Kylie D.

Ecotoxicology. 2022 Sept., v. 31, no. 7

2022

Abstract	Mercury (Hg) is a widespread and harmful persistent pollutant of aquatic ecosystems. Except for the northern most populations of American alligators (Alligator Mississippiensis) found in North Carolina, the potential adverse health impacts of Hg on ecosystems and humans consuming alligator meat have been studied for over three decades. Now that alligators are being recreationally hunted and consumed across their range, it is especially important to monitor toxic contaminant levels to best understand possible adverse impacts of exposures on alligator populations and human health. In this study, we determined blood Hg concentrations in American alligators from an urbanized site in Wilmington, NC, a nearby site at Lake Waccamaw, NC, and a site on the St Johns River in Florida. Median blood total Hg (tHg) concentrations were particularly high at Lake Waccamaw (526 ng/g, range 152–946 ng/g), resulting in median muscle concentrations (0.48 mg/kg, range 0.13–0.88 mg/kg) well above US EPA screening values for fish consumption. Median concentrations at the Wilmington site (69 ng/g, range 22–336 ng/g) were generally low, and Hg concentrations from the St Johns River site (143 ng/g, range 54–244 ng/g) were comparable to those reported in previous studies. Analysis of relationships between tHg concentrations and a panel of blood chemistry biomarkers found only modest concentration-dependent impact on biomarkers of renal function. The results of this study reveal that local environmental factors greatly impact Hg bioaccumulation in alligators, findings that reaffirm local contaminant biomonitoring in alligator populations will be critical for affective management and determination of guidelines for safe consumption of harvested alligators.
Keywords	Alligator mississippiensis ; United States Environmental Protection Agency ; alligators ; bioaccumulation ; biomarkers ; blood ; blood chemistry ; ecotoxicology ; environmental monitoring ; fish consumption ; human health ; lakes ; meat ; mercury ; muscles ; pollutants ; renal function ; rivers ; toxicity ; urbanization ; Florida ; North Carolina
Language	English
Dates of publication	2022-09
Size	p. 1137-1146.
Publishing place	Springer US
Document type	Article
ZDB-ID	34042-x
ISSN	1573-3017 ; 0963-9292
ISSN (online)	1573-3017
ISSN	0963-9292
DOI	10.1007/s10646-022-02573-z
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Rapid Characterization of Human Serum Albumin Binding for Per- and Polyfluoroalkyl Substances Using Differential Scanning Fluorimetry.

Jackson, Thomas W / Scheibly, Chris M / Polera, M E / Belcher, Scott M

Environmental science & technology

2021 Volume 55, Issue 18, Page(s) 12291–12301

Abstract: Per- and polyfluoroalkyl substances (PFAS) are a diverse class of synthetic chemicals that accumulate in the environment. Many proteins, including the primary human serum transport protein albumin (HSA), bind PFAS. The predictive power of physiologically ...

Abstract	Per- and polyfluoroalkyl substances (PFAS) are a diverse class of synthetic chemicals that accumulate in the environment. Many proteins, including the primary human serum transport protein albumin (HSA), bind PFAS. The predictive power of physiologically based pharmacokinetic modeling approaches is currently limited by a lack of experimental data defining albumin-binding properties for most PFAS. A novel thermal denaturation assay was optimized to evaluate changes in the thermal stability of HSA in the presence of increasing concentrations of known ligands and a structurally diverse set of PFAS. Assay performance was initially evaluated for fatty acids and HSA-binding drugs ibuprofen and warfarin. Concentration-response relationships were determined and dissociation constants (
MeSH term(s)	Alkanesulfonic Acids ; Carboxylic Acids ; Fluorocarbons ; Fluorometry ; Humans ; Serum Albumin, Human ; Sulfonic Acids
Chemical Substances	Alkanesulfonic Acids ; Carboxylic Acids ; Fluorocarbons ; Sulfonic Acids ; Serum Albumin, Human (ZIF514RVZR)
Language	English
Publishing date	2021-09-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1520-5851
ISSN (online)	1520-5851
DOI	10.1021/acs.est.1c01200
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