Behavioral Screening for Toxicology and Safety Pharmacology

Moser, Virginia C.; Kallman, Mary Jeanne

doi:10.1016/b978-0-12-801238-3.02204-2

“…Like human neurological exams, rodent observational batteries often serve as a first-tier test to identify “an effect.” Examples include the Functional Observational Battery ( US EPA, 1994b ; Moser and Kallman, 2018 ; Gauvin, 2021 ) and the SmithKline, Harwell, Imperial College, Royal Hospital, Phenotype Assessment (SHIRPA) ( Rogers et al, 2001 ; Lalonde et al, 2021 ). Additional batteries have been developed for assessing vestibular dysfunction ( Maroto et al, 2021 ), various genetic manipulations ( Brown et al, 2000 ), and neonatal function ( Fox, 1965 ; Brown et al, 2000 ; Feather-Schussler and Ferguson, 2016 ; Soria-Ortiz et al, 2021 ).…”

Section: Behavioral Assessmentsmentioning

confidence: 99%

Roadbumps at the Crossroads of Integrating Behavioral and In Vitro Approaches for Neurotoxicity Assessment

Harry¹,

McBride²,

Witchey³

et al. 2022

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With the appreciation that behavior represents the integration and complexity of the nervous system, neurobehavioral phenotyping and assessment has seen a renaissance over the last couple of decades, resulting in a robust database on rodent performance within various testing paradigms, possible associations with human disorders, and therapeutic interventions. The interchange of data across behavior and other test modalities and multiple model systems has advanced our understanding of fundamental biology and mechanisms associated with normal functions and alterations in the nervous system. While there is a demonstrated value and power of neurobehavioral assessments for examining alterations due to genetic manipulations, maternal factors, early development environment, the applied use of behavior to assess environmental neurotoxicity continues to come under question as to whether behavior represents a sensitive endpoint for assessment. Why is rodent behavior a sensitive tool to the neuroscientist and yet, not when used in pre-clinical or chemical neurotoxicity studies? Applying new paradigms and evidence on the biological basis of behavior to neurobehavioral testing requires expertise and refinement of how such experiments are conducted to minimize variability and maximize information. This review presents relevant issues of methods used to conduct such test, sources of variability, experimental design, data analysis, interpretation, and reporting. It presents beneficial and critical limitations as they translate to the in vivo environment and considers the need to integrate across disciplines for the best value. It proposes that a refinement of behavioral assessments and understanding of subtle pronounced differences will facilitate the integration of data obtained across multiple approaches and to address issues of translation.

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“…For the assessment of neurotoxicology, the FOB is often used (Moser, 1991). The differences between the two assays are subtle (Moser & Kallman, 2018). The procedures are essentially the same, but when considering neurotoxicology, the FOB is conducted under GLP guidelines using more animals per group, with the doses used being low enough for a no‐effect level determination and high enough to see marked nervous system behaviors.…”

Section: Introductionmentioning

confidence: 99%

The Irwin Test and Functional Observational Battery (FOB) for Assessing the Effects of Compounds on Behavior, Physiology, and Safety Pharmacology in Rodents

Mathiasen

¹

,

Moser

²

2023

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The modified Irwin procedure or functional observational battery (FOB) can be used to achieve several goals. New chemical entities (NCEs) can be behaviorally screened for nervous system effects at a variety of doses to identify potential therapeutic uses and in the selection of appropriate doses for subsequent assays. NCEs can also be evaluated in the behavioral battery and compared with reference standards to assess liabilities in a new compound class, with an estimated therapeutic index being suggested by the doses used in comparison to therapeutic doses. For the assessment of neurotoxicology, the FOB is often used. The differences between the two assays are subtle. The procedures used are essentially the same, but when considering neurotoxicology, the FOB is often conducted using GLP guidelines, with more animals being used per group, and doses that are low enough to determine a no effect level and high enough to induce marked nervous system behaviors. © 2023 Wiley Periodicals LLC. Basic Protocol: The Irwin test and FOB for assessing the effects of compounds on behavior, physiology, and safety pharmacology in rodents

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“…For the assessment of neurotoxicology, the FOB is often used (Moser, ). The differences between the two assays are subtle (Moser & Kallman, ). The procedures are essentially the same, but when considering neurotoxicology, the FOB is conducted under GLP guidelines, using more animals per group, with the doses used being low enough for a no‐effect level determination and high enough to see marked nervous system behaviors.…”

Section: Introductionmentioning

confidence: 99%

The Irwin Test and Functional Observational Battery (FOB) for Assessing the Effects of Compounds on Behavior, Physiology, and Safety Pharmacology in Rodents

Mathiasen

¹

,

Moser

²

2018

View full text Add to dashboard Cite

The modified Irwin procedure or functional observational battery (FOB) can be used to achieve several goals. New chemical entities (NCEs) can be behaviorally screened for nervous system effects at a variety of doses to identify potential therapeutic uses and in the selection of appropriate doses for subsequent assays. NCEs can also be evaluated in the behavioral battery and compared with reference standards to assess liabilities in a new compound class, with an estimated therapeutic index being suggested by the doses used in comparison to therapeutic doses. For the assessment of neurotoxicology, the FOB is often used. The differences between the two assays are subtle. The procedures used are essentially the same, but when considering neurotoxicology, the FOB is often conducted using GLP guidelines, with more animals being used per group, and doses that are low enough to determine a no effect level and high enough to induce marked nervous system behaviors. © 2018 by John Wiley & Sons, Inc.

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Behavioral Screening for Toxicology and Safety Pharmacology

Cited by 5 publications

References 114 publications

Roadbumps at the Crossroads of Integrating Behavioral and In Vitro Approaches for Neurotoxicity Assessment

Roadbumps at the Crossroads of Integrating Behavioral and In Vitro Approaches for Neurotoxicity Assessment

The Irwin Test and Functional Observational Battery (FOB) for Assessing the Effects of Compounds on Behavior, Physiology, and Safety Pharmacology in Rodents

The Irwin Test and Functional Observational Battery (FOB) for Assessing the Effects of Compounds on Behavior, Physiology, and Safety Pharmacology in Rodents

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