Neurotoxicity of Halogenated Organic Compounds

1st Edition, Volume 10 - October 25, 2023
Editors: Lucio G. Costa, Michael Aschner, Prasada Rao S. Kodavanti
Language: English
Hardback ISBN:
9 7 8 - 0 - 4 4 3 - 1 3 3 4 0 - 4
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 1 3 3 4 1 - 1

Neurotoxicity of Halogenated Organic Compounds, Volume 10 covers three groups of Halogenated Organic Compounds (Chlorinated, Brominated, and Fluorinated Compounds) that are legac… Read more

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Neurotoxicity of Halogenated Organic Compounds, Volume 10 covers three groups of Halogenated Organic Compounds (Chlorinated, Brominated, and Fluorinated Compounds) that are legacy and emerging contaminants, providing background information, characteristics, physicochemical properties, environmental contamination, and human exposure. Specific chapters covered in this release include Perspective on Halogenated Organic Compounds, The Neurotoxicity of Polychlorinated Biphenyls (PCBs), Neuroendocrine Effects of Polychlorinated Biphenyls (PCBs), Mechanisms of PCB Neurotoxicity: AHR and THR Dogma meet RYR reality, Microbiome and the Neurotoxicity of Brominated Flame Retardants (BFRs), and much more.

Other chapters cover Neuroendocrine Effects of Brominated Flame Retardants (BFRs), Focused on Polybrominated Diphenyl Ethers (PBDEs), Neurochemical Effects of Halogenated Organic Compounds: Possible Mode(s) of action and Structure-Activity Relationships, The Neurotoxic Effects of Perfluoroalkyl Substances (PFAS) in Animal Models and Human Cohorts, Neurochemical Mechanisms of Perfluoroalkyl Substances (PFAS) Neurotoxic Action, and Future Directions and Regulatory aspects of Halogenated Organic Compounds.

Cover image
Title page
Table of Contents
Copyright
Contributors
Preface
Chapter One: Perspective on halogenated organic compounds
Abstract
1 Introduction
2 Background and classes of HOCs
3 Summary and conclusions
Acknowledgments
References
Further reading
Chapter Two: The neurotoxicity of polychlorinated biphenyls (PCBs)
Abstract
1 Introduction
2 Human studies
3 Experimental animal studies
4 Conclusions
Acknowledgments
References
Chapter Three: Neuroendocrine effects of polychlorinated biphenyls (PCBs)
Abstract
1 Introduction
2 Overview of the hypothalamic–pituitary–gonadal and hypothalamic–pituitary–thyroid neuroendocrine systems
3 PCBs as environmental neuroendocrine disruptors
4 PCBs effects on the hypothalamic–pituitary-gonadal axis
5 PCBs and the hypothalamic–pituitary-thyroid axis
6 Neuroendocrine effects of PCBs on the hypothalamo-neurohypophysial system (HNS)
7 Inter- and transgenerational effects of PCBs on neuroendocrine systems
8 The future of toxicity testing for endocrine disruption: The ATHENA project on thyroid hormone system disruptors
Acknowledgments
References
Chapter Four: Ryanodine receptor-dependent mechanisms of PCB developmental neurotoxicity
Abstract
1 Introduction
2 PCB–RyR interactions
3 RyR-dependent cellular effects of PCBs
4 Evidence that RyR sensitization mediates the behavioral effects of PCBs
5 Implications of RyR-dependent mechanisms of PCB developmental neurotoxicity
6 Conclusions
Acknowledgments
References
Chapter Five: The microbiome/microbiota and the neurotoxicity of polybrominated diphenyl ether (PBDE) flame retardants
Abstract
1 PBDEs: Uses, contamination, and body burden
2 Kinetics of PBDEs and structure–activity relationship considerations
3 PBDEs: Adverse health effects
4 Neurotoxicity of PBDEs
5 Possible mechanisms of PBDE developmental neurotoxicity
6 An overview of the microbiome and microbiota
7 PBDEs and the microbiota
8 Effects of PBDEs on the microbiota and its association with neurotoxicity
9 Conclusions and future avenues for research
Acknowledgments
References
Chapter Six: Neuroendocrine effects of brominated flame retardants, focused on polybrominated diphenyl ethers
Abstract
1 Introduction
2 General characteristics of the main BFRs
3 Overview of the neuroendocrine system
4 Neuroendocrine disruption by BFRs
5 Neuroendocrine effects of PBDEs
6 Neuroendocrine effects of PBBs
7 Neuroendocrine effects of HBCD
8 Neuroendocrine effects of TBBPA
9 Neuroendocrine effects of NBFRs
10 General conclusions
Acknowledgments
References
Chapter Seven: Neurochemical effects of halogenated organic compounds: Possible adverse outcome pathways and structure–activity relationships
Abstract
1 Introduction
2 Human (epidemiological studies) evidence of neurotoxicity by HOCs (PCBs and PBDEs)
3 Evidence of neurotoxicity in animals by HOCs (PCBs and PBDEs)
4 Neurotoxicity of HOCs (PCBs and PBDEs)—Potential adverse outcome pathways
5 Structure–activity relationships among HOCs (PCBs and PBDEs) on intracellular signaling events (PKC translocation and calcium buffering)
6 Summary and future directions
Acknowledgments
References
Chapter Eight: Neurotoxicity of poly- and perfluoroalkyl substances (PFAS): Epidemiological and rodent studies of behavioral outcomes
Abstract
1 Introduction
2 PFAS and epidemiological studies
3 PFAS and rodent studies
4 Conclusions
Acknowledgments
References
Chapter Nine: Neurochemical mechanisms of perfluoroalkyl substances (PFAS) neurotoxic action
Abstract
1 PFAS absorption and deposition in the brain
2 PFAS effects on neurotransmitters
3 PFAS and neuronal calcium signaling
4 Functional consequences of PFAS exposure and disease risk
5 Conclusions
References
Chapter Ten: Risk assessment, risk management, and regulation of halogenated organic chemicals: Current practice and future directions
Abstract
1 Overview of risk assessment
2 Testing industrial and environmental chemicals for neurotoxicity
3 Analytical challenges and advanced methodologies for characterizing HOCs
4 Current U.S. federal and state legislation for regulating HOCs
5 Future directions for improving risk assessment and risk management of HOCs
6 Summary
Acknowledgments
References

Lucio G. Costa

Dr. Lucio G. Costa is Professor of Toxicology at the University of Washington in Seattle, and of Pharmacology/Toxicology at the University of Parma Medical School. He received a doctorate in Pharmacology from the University of Milano in 1977, and was a postdoctoral fellow at the University of Texas at Houston. He is a member of several national and international professional organizations, a Fellow of the Academy of Toxicological Sciences, and a European Certified Toxicologist. He received various award for his scientific accomplishments, including the Achievement Award from the Society of Toxicology. He serves in various editorial capacities for several toxicology journals, and is an active manuscript and grant reviewer. Dr. Costa has been the member of dozens of panels and committees at the national and international level dealing with toxicology and risk assessment issues. He has chaired and/or organized symposia at scientific meetings in the United States and internationally. He has been teaching classes in the area of toxicology, neurotoxicology and pharmacology to graduate and medical students for 30 years. He keeps an active research program in the area of neurotoxicology.

Affiliations and expertise

Professor of Toxicology, University of Washington, Seattle, WA, USA

Michael Aschner

Dr. Aschner serves as the Harold and Muriel Block Chair in Molecular Pharmacology at Albert Einstein College of Medicine. He served on numerous toxicology panels (Institute of Medicine, US Environmental Protection Agency, Center for Disease Control), and is a member of the Neurotoxicology and Alcohol study section (NIH). Research in our lab focuses on the following topics: (1) Modulation of C. elegans genes (aat, skn-1, daf-16) that are homologous to mammalian regulators of MeHg uptake and cellular resistance will modify dopaminergic neurodegeneration in response to MeHg exposure. (2) Under conditions of MeHg-induced oxidative stress, Nrf2 (a master regulator of antioxidant responses) coordinates the upregulation of cytoprotective genes that combat MeHg-induced oxidative injury, and that genetic and biochemical changes that negatively impact upon Nrf2 function increase MeHg’s neurotoxicity. (3) PARK2, a strong PD genetic risk factor, alters neuronal vulnerability to modifiers of cellular Mn status, particularly at the level of mitochondrial dysfunction and oxidative stress. Our studies are designed to (1) shed novel mechanistic insight into metal-induced neurodegeneration; (2) identify targets for genetic or pharmacologic modulation of neurodegenerative disorders; (3) increase knowledge of the pathway involved in oxidative stress; (4) develop improved research models for human disease using knowledge of environmental sciences.

Affiliations and expertise

Professor, Department of Molecular Pharmacology, Albert Einstein College of Medicine, NY, USA

Prasada Rao S. Kodavanti

Dr. Prasada Kodavanti is a Senior Research Toxicologist at the Neurological & Endocrine toxicology branch of Public Health & Integrated Toxicology Division at CPHEA/ORD, U.S. Environmental Protection Agency in Research Triangle Park, NC, USA. In this role, he leads a team of scientists to develop in vitro models based on adverse outcome pathways (AOPs) and O’mics technology in New Approach Methods (NAMs) by selecting a few chemicals for initial testing. The goal is to develop efficient NAMs based on O’mics for screening and prioritization of untested chemicals and also provide scientific support for the existing NAMs such as neurite outgrowth and microelectrode array assays. He also plays a key role in the Safe and Healthy Communities project related to understanding the interaction between chemical stressors and non-chemical factors and develop genomic biomarkers in blood to identify vulnerable communities. He joined the USEPA as a Toxicologist in January of 1995. Dr. Kodavanti is a recognized scientist internationally in the area of halogenated organic compounds and adult/developmental neurotoxicity. Dr. Kodavanti is an extremely prolific researcher with over 125 peer-reviewed journal articles. In addition, he is primary author on 26 book chapters as well as 8 review articles. His publications appear in a wide variety of leading scientific journals and is well quoted by scientists in this field. In 1996, one of his papers won the prestigious Society of Toxicology’s Board of Publications Award for the Best Paper in Toxicology and Applied Pharmacology. He received USEPA’s 1996, 1999, 2002, and 2012 Scientific and Technological Achievement (STAA) Award. In 2009, he received STAA level 1 award (highest scientific award by USEPA) for highlighting genomics in understanding mode of action in developmental neurotoxicity. Dr. Kodavanti gave several invited presentations at national and international meetings. Dr. Kodavanti served as session chair in several conferences and a member of Special session organizing committee of the Dioxin ’97. He is a member of the Advisory Board for several journals and current ones include “The Open Toxicology” and “Neurotoxicology”. He was an Associate Editor for the journal “Drug and Chemical Toxicology”. Dr. Kodavanti is also an Adjunct Professor of Toxicology, School of Pharmacy at University of Rhode Island, Kingston, RI since April 2000. He is also a reviewer for a number of International scientific journals.

Affiliations and expertise

Neurological and Endocrine Toxicology Branch, Public Health and Integrated Toxicology Division, U.S. Environmental Protection Agency, USA

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Neurotoxicity of Halogenated Organic Compounds

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Lucio G. Costa

Michael Aschner

Prasada Rao S. Kodavanti