The Experts below are selected from a list of 306 Experts worldwide ranked by ideXlab platform
Edward J. Calabrese - One of the best experts on this subject based on the ideXlab platform.
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Improved Approaches to Dose–Response Modeling of Toxicological and Adaptive Endpoints for Risk Assessment: Hormetic Dose Response
Comprehensive Toxicology, 2018Co-Authors: Edward J. CalabreseAbstract:This article provides a general description and evaluation of the hormetic biphasic Dose–Response relationship, including its historical foundation, how it became marginalized in the early part of the 20th century, and why it has experienced a strong resurgence in interest and application over the past several decades. The article provides scientific documentation concerning the occurrence, frequency, generality, and mechanistic basis for hormetic Dose Responses. Hormetic effects occur without restriction to biological model, cell type, endpoint measured, inducing agent, and level of biological organization (cell, organ, and organism). The quantitative features of hormetic Dose Responses are also independent of mechanism. The hormetic Dose Response has also outcompeted both the threshold and linear nonthreshold models in making accurate predictions in the low-Dose zone using multiple large datasets with a wide range of models, agents, and endpoints. Particular attention is also given to how risk assessment methods can integrate the hormetic concept for carcinogens and noncarcinogens, improve the accuracy of low-Dose risk estimates, and enhance public health outcomes. The hormetic Dose Response is therefore central to biology, toxicology, pharmacology, and public health and needs to be incorporated into governmental risk assessment procedures.
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improved approaches to Dose Response modeling of toxicological and adaptive endpoints for risk assessment hormetic Dose Response
Reference Module in Biomedical Sciences#R##N#Comprehensive Toxicology (Third Edition), 2018Co-Authors: Edward J. CalabreseAbstract:This article provides a general description and evaluation of the hormetic biphasic Dose–Response relationship, including its historical foundation, how it became marginalized in the early part of the 20th century, and why it has experienced a strong resurgence in interest and application over the past several decades. The article provides scientific documentation concerning the occurrence, frequency, generality, and mechanistic basis for hormetic Dose Responses. Hormetic effects occur without restriction to biological model, cell type, endpoint measured, inducing agent, and level of biological organization (cell, organ, and organism). The quantitative features of hormetic Dose Responses are also independent of mechanism. The hormetic Dose Response has also outcompeted both the threshold and linear nonthreshold models in making accurate predictions in the low-Dose zone using multiple large datasets with a wide range of models, agents, and endpoints. Particular attention is also given to how risk assessment methods can integrate the hormetic concept for carcinogens and noncarcinogens, improve the accuracy of low-Dose risk estimates, and enhance public health outcomes. The hormetic Dose Response is therefore central to biology, toxicology, pharmacology, and public health and needs to be incorporated into governmental risk assessment procedures.
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Food safety and security and the Dose-Response
Food Security, 2012Co-Authors: Edward J. CalabreseAbstract:Getting the Dose-Response right is a critical component in the assessment of chemical food safety. Being able to validate Dose-Response model predictions in the low-Dose zone would be a critical aspect of the assurances that correct decisions about food safety and security are made. The present paper examines the history of the threshold Dose-Response model and how it became incorporated into governmental regulatory and risk assessment activities, including those affecting chemical food safety. The present analysis reveals that the major risk assessment models used by international regulatory agencies, such as the threshold Dose-Response model, were never validated prior to their acceptance and use by international regulatory agencies. Furthermore, once they were tested both the threshold and linear Dose-Response models failed to make accurate predictions in the low-Dose zone. The only model providing accurate predictions in the low Dose zone was the hormetic Dose-Response, a model not used by regulatory agencies. The present analysis raises important new questions for the risk assessment process in general and that of chemical food security in particular.
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U-Shaped Dose Response in Behavioral Pharmacology: Historical Foundations
Critical reviews in toxicology, 2008Co-Authors: Edward J. CalabreseAbstract:This article assesses the historical foundations of U-shaped Dose-Responses in behavioral pharmacology and toxicology with particular emphasis on schedules of reinforcement. Quantitative features of the drug Dose Response, which are consistent with the hormetic Dose Response model, are detailed along with possible mechanistic foundations to account for low-Dose stimulation and high-Dose inhibition Responses. The article provides a reinterpretation of the biphasic Dose Response in the fixed interval (FI) schedule of reinforcement.
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Alzheimer's Disease Drugs: An Application of the Hormetic Dose-Response Model
Critical reviews in toxicology, 2008Co-Authors: Edward J. CalabreseAbstract:This article provides an evaluation of the Dose-Response features of drugs that are intended to improve memory, some of which have been used in the treatment of Alzheimer's disease (AD). A common feature of these drugs is that they act via an inverted U-shaped Dose Response, consistent with the hormetic Dose Response model. This article assesses historical foundations that lead to the development of AD drugs, their Dose-Response features and how the quantitative features of such Dose Responses affected drug discovery and development, and the successes and possible failures of such agents in preclinical and clinical settings. This story begins about 150 years ago with the discovery of an active agent in the Calabar bean plant called physostigmine, its unfolding medical applications, and its implications for Dose-Response relationships, memory enhancement, and improved drug discovery activities. The article also demonstrates the occurrence of U-shaped Dose Responses for memory with numerous endogenous agonists including neurosteroids, various peptides (e.g., vasopressin, CCK-8, neuropeptide Y), and other agents (e.g., epinephrine, antagonists for platelet activity factor and nicotinic receptors), supporting the generalizability of the hormetic biphasic Dose Response. Finally, the significance of the U-shaped Dose Response is critical for successful clinical application, since it defines the therapeutic window.
Ted W Simon - One of the best experts on this subject based on the ideXlab platform.
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The use of mode of action information in risk assessment: Quantitative key events/Dose-Response framework for modeling the Dose-Response for key events
Critical Reviews in Toxicology, 2014Co-Authors: Ted W Simon, S Stoney Simons, R Julian Preston, Alan R Boobis, Samuel M Cohen, Nancy G Doerrer, Penelope A Fenner-crisp, Tami S Mcmullin, Charlene A Mcqueen, J Craig RowlandsAbstract:AbstractThe HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Action/Human Relevance Framework and Key Events/Dose Response Framework (KEDRF) to make the best use of quantitative Dose-Response and timing information for Key Events (KEs). The resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a structured quantitative approach for systematic examination of the Dose-Response and timing of KEs resulting from a Dose of a bioactive agent that causes a potential adverse outcome. Two concepts are described as aids to increasing the understanding of mode of action—Associative Events and Modulating Factors. These concepts are illustrated in two case studies; 1) cholinesterase inhibition by the pesticide chlorpyrifos, which illustrates the necessity of considering quantit...
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the use of mode of action information in risk assessment quantitative key events Dose Response framework for modeling the Dose Response for key events
Critical Reviews in Toxicology, 2014Co-Authors: Ted W Simon, S Stoney Simons, Alan R Boobis, Samuel M Cohen, Nancy G Doerrer, Tami S Mcmullin, Charlene A Mcqueen, Julian R Preston, Penelope A Fennercrisp, Craig J RowlandsAbstract:AbstractThe HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Action/Human Relevance Framework and Key Events/Dose Response Framework (KEDRF) to make the best use of quantitative Dose-Response and timing information for Key Events (KEs). The resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a structured quantitative approach for systematic examination of the Dose-Response and timing of KEs resulting from a Dose of a bioactive agent that causes a potential adverse outcome. Two concepts are described as aids to increasing the understanding of mode of action—Associative Events and Modulating Factors. These concepts are illustrated in two case studies; 1) cholinesterase inhibition by the pesticide chlorpyrifos, which illustrates the necessity of considering quantit...
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The use of mode of action information in risk assessment: quantitative key events/Dose-Response framework for modeling the Dose-Response for key events.
Critical reviews in toxicology, 2014Co-Authors: Ted W Simon, S Stoney Simons, R Julian Preston, Alan R Boobis, Samuel M Cohen, Nancy G Doerrer, Penelope A Fenner-crisp, Tami S Mcmullin, Charlene A Mcqueen, J Craig RowlandsAbstract:The HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Action/Human Relevance Framework and Key Events/Dose Response Framework (KEDRF) to make the best use of quantitative Dose-Response and timing information for Key Events (KEs). The resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a structured quantitative approach for systematic examination of the Dose-Response and timing of KEs resulting from a Dose of a bioactive agent that causes a potential adverse outcome. Two concepts are described as aids to increasing the understanding of mode of action-Associative Events and Modulating Factors. These concepts are illustrated in two case studies; 1) cholinesterase inhibition by the pesticide chlorpyrifos, which illustrates the necessity of considering quantitative Dose-Response information when assessing the effect of a Modulating Factor, that is, enzyme polymorphisms in humans, and 2) estrogen-induced uterotrophic Responses in rodents, which demonstrate how quantitative Dose-Response modeling for KE, the understanding of temporal relationships between KEs and a counterfactual examination of hypothesized KEs can determine whether they are Associative Events or true KEs.
J Craig Rowlands - One of the best experts on this subject based on the ideXlab platform.
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The use of mode of action information in risk assessment: Quantitative key events/Dose-Response framework for modeling the Dose-Response for key events
Critical Reviews in Toxicology, 2014Co-Authors: Ted W Simon, S Stoney Simons, R Julian Preston, Alan R Boobis, Samuel M Cohen, Nancy G Doerrer, Penelope A Fenner-crisp, Tami S Mcmullin, Charlene A Mcqueen, J Craig RowlandsAbstract:AbstractThe HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Action/Human Relevance Framework and Key Events/Dose Response Framework (KEDRF) to make the best use of quantitative Dose-Response and timing information for Key Events (KEs). The resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a structured quantitative approach for systematic examination of the Dose-Response and timing of KEs resulting from a Dose of a bioactive agent that causes a potential adverse outcome. Two concepts are described as aids to increasing the understanding of mode of action—Associative Events and Modulating Factors. These concepts are illustrated in two case studies; 1) cholinesterase inhibition by the pesticide chlorpyrifos, which illustrates the necessity of considering quantit...
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The use of mode of action information in risk assessment: quantitative key events/Dose-Response framework for modeling the Dose-Response for key events.
Critical reviews in toxicology, 2014Co-Authors: Ted W Simon, S Stoney Simons, R Julian Preston, Alan R Boobis, Samuel M Cohen, Nancy G Doerrer, Penelope A Fenner-crisp, Tami S Mcmullin, Charlene A Mcqueen, J Craig RowlandsAbstract:The HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Action/Human Relevance Framework and Key Events/Dose Response Framework (KEDRF) to make the best use of quantitative Dose-Response and timing information for Key Events (KEs). The resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a structured quantitative approach for systematic examination of the Dose-Response and timing of KEs resulting from a Dose of a bioactive agent that causes a potential adverse outcome. Two concepts are described as aids to increasing the understanding of mode of action-Associative Events and Modulating Factors. These concepts are illustrated in two case studies; 1) cholinesterase inhibition by the pesticide chlorpyrifos, which illustrates the necessity of considering quantitative Dose-Response information when assessing the effect of a Modulating Factor, that is, enzyme polymorphisms in humans, and 2) estrogen-induced uterotrophic Responses in rodents, which demonstrate how quantitative Dose-Response modeling for KE, the understanding of temporal relationships between KEs and a counterfactual examination of hypothesized KEs can determine whether they are Associative Events or true KEs.
Tami S Mcmullin - One of the best experts on this subject based on the ideXlab platform.
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The use of mode of action information in risk assessment: Quantitative key events/Dose-Response framework for modeling the Dose-Response for key events
Critical Reviews in Toxicology, 2014Co-Authors: Ted W Simon, S Stoney Simons, R Julian Preston, Alan R Boobis, Samuel M Cohen, Nancy G Doerrer, Penelope A Fenner-crisp, Tami S Mcmullin, Charlene A Mcqueen, J Craig RowlandsAbstract:AbstractThe HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Action/Human Relevance Framework and Key Events/Dose Response Framework (KEDRF) to make the best use of quantitative Dose-Response and timing information for Key Events (KEs). The resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a structured quantitative approach for systematic examination of the Dose-Response and timing of KEs resulting from a Dose of a bioactive agent that causes a potential adverse outcome. Two concepts are described as aids to increasing the understanding of mode of action—Associative Events and Modulating Factors. These concepts are illustrated in two case studies; 1) cholinesterase inhibition by the pesticide chlorpyrifos, which illustrates the necessity of considering quantit...
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the use of mode of action information in risk assessment quantitative key events Dose Response framework for modeling the Dose Response for key events
Critical Reviews in Toxicology, 2014Co-Authors: Ted W Simon, S Stoney Simons, Alan R Boobis, Samuel M Cohen, Nancy G Doerrer, Tami S Mcmullin, Charlene A Mcqueen, Julian R Preston, Penelope A Fennercrisp, Craig J RowlandsAbstract:AbstractThe HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Action/Human Relevance Framework and Key Events/Dose Response Framework (KEDRF) to make the best use of quantitative Dose-Response and timing information for Key Events (KEs). The resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a structured quantitative approach for systematic examination of the Dose-Response and timing of KEs resulting from a Dose of a bioactive agent that causes a potential adverse outcome. Two concepts are described as aids to increasing the understanding of mode of action—Associative Events and Modulating Factors. These concepts are illustrated in two case studies; 1) cholinesterase inhibition by the pesticide chlorpyrifos, which illustrates the necessity of considering quantit...
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The use of mode of action information in risk assessment: quantitative key events/Dose-Response framework for modeling the Dose-Response for key events.
Critical reviews in toxicology, 2014Co-Authors: Ted W Simon, S Stoney Simons, R Julian Preston, Alan R Boobis, Samuel M Cohen, Nancy G Doerrer, Penelope A Fenner-crisp, Tami S Mcmullin, Charlene A Mcqueen, J Craig RowlandsAbstract:The HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Action/Human Relevance Framework and Key Events/Dose Response Framework (KEDRF) to make the best use of quantitative Dose-Response and timing information for Key Events (KEs). The resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a structured quantitative approach for systematic examination of the Dose-Response and timing of KEs resulting from a Dose of a bioactive agent that causes a potential adverse outcome. Two concepts are described as aids to increasing the understanding of mode of action-Associative Events and Modulating Factors. These concepts are illustrated in two case studies; 1) cholinesterase inhibition by the pesticide chlorpyrifos, which illustrates the necessity of considering quantitative Dose-Response information when assessing the effect of a Modulating Factor, that is, enzyme polymorphisms in humans, and 2) estrogen-induced uterotrophic Responses in rodents, which demonstrate how quantitative Dose-Response modeling for KE, the understanding of temporal relationships between KEs and a counterfactual examination of hypothesized KEs can determine whether they are Associative Events or true KEs.
Nancy G Doerrer - One of the best experts on this subject based on the ideXlab platform.
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The use of mode of action information in risk assessment: Quantitative key events/Dose-Response framework for modeling the Dose-Response for key events
Critical Reviews in Toxicology, 2014Co-Authors: Ted W Simon, S Stoney Simons, R Julian Preston, Alan R Boobis, Samuel M Cohen, Nancy G Doerrer, Penelope A Fenner-crisp, Tami S Mcmullin, Charlene A Mcqueen, J Craig RowlandsAbstract:AbstractThe HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Action/Human Relevance Framework and Key Events/Dose Response Framework (KEDRF) to make the best use of quantitative Dose-Response and timing information for Key Events (KEs). The resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a structured quantitative approach for systematic examination of the Dose-Response and timing of KEs resulting from a Dose of a bioactive agent that causes a potential adverse outcome. Two concepts are described as aids to increasing the understanding of mode of action—Associative Events and Modulating Factors. These concepts are illustrated in two case studies; 1) cholinesterase inhibition by the pesticide chlorpyrifos, which illustrates the necessity of considering quantit...
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the use of mode of action information in risk assessment quantitative key events Dose Response framework for modeling the Dose Response for key events
Critical Reviews in Toxicology, 2014Co-Authors: Ted W Simon, S Stoney Simons, Alan R Boobis, Samuel M Cohen, Nancy G Doerrer, Tami S Mcmullin, Charlene A Mcqueen, Julian R Preston, Penelope A Fennercrisp, Craig J RowlandsAbstract:AbstractThe HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Action/Human Relevance Framework and Key Events/Dose Response Framework (KEDRF) to make the best use of quantitative Dose-Response and timing information for Key Events (KEs). The resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a structured quantitative approach for systematic examination of the Dose-Response and timing of KEs resulting from a Dose of a bioactive agent that causes a potential adverse outcome. Two concepts are described as aids to increasing the understanding of mode of action—Associative Events and Modulating Factors. These concepts are illustrated in two case studies; 1) cholinesterase inhibition by the pesticide chlorpyrifos, which illustrates the necessity of considering quantit...
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The use of mode of action information in risk assessment: quantitative key events/Dose-Response framework for modeling the Dose-Response for key events.
Critical reviews in toxicology, 2014Co-Authors: Ted W Simon, S Stoney Simons, R Julian Preston, Alan R Boobis, Samuel M Cohen, Nancy G Doerrer, Penelope A Fenner-crisp, Tami S Mcmullin, Charlene A Mcqueen, J Craig RowlandsAbstract:The HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Action/Human Relevance Framework and Key Events/Dose Response Framework (KEDRF) to make the best use of quantitative Dose-Response and timing information for Key Events (KEs). The resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a structured quantitative approach for systematic examination of the Dose-Response and timing of KEs resulting from a Dose of a bioactive agent that causes a potential adverse outcome. Two concepts are described as aids to increasing the understanding of mode of action-Associative Events and Modulating Factors. These concepts are illustrated in two case studies; 1) cholinesterase inhibition by the pesticide chlorpyrifos, which illustrates the necessity of considering quantitative Dose-Response information when assessing the effect of a Modulating Factor, that is, enzyme polymorphisms in humans, and 2) estrogen-induced uterotrophic Responses in rodents, which demonstrate how quantitative Dose-Response modeling for KE, the understanding of temporal relationships between KEs and a counterfactual examination of hypothesized KEs can determine whether they are Associative Events or true KEs.