CNS Safety Screening Under ICH S7A Guidelines Requires Observations of Multiple Behavioral Units to Assess Motor Function
| Autor: | Mary-Jeanne Kallman, Jill A. Dalton, Theodore J. Baird, Zachary J. Zimmermann, David V. Gauvin |
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| Rok vydání: | 2019 |
| Předmět: |
Predictive validity
Central Nervous System medicine.medical_specialty Drug Evaluation Preclinical Harmonization Guidelines as Topic Motor Activity Toxicology Motor function 050105 experimental psychology 03 medical and health sciences 0302 clinical medicine Physical medicine and rehabilitation Toxicity Tests Medicine General activity Animals 0501 psychology and cognitive sciences End point Behavior Animal business.industry Safety pharmacology 05 social sciences Motor control Home cage Neurotoxicity Syndromes business 030217 neurology & neurosurgery |
| Zdroj: | International journal of toxicology. 38(5) |
| ISSN: | 1092-874X |
| Popis: | In the adoption of behavior as a critical end point in safety pharmacology and neurotoxicity screening, federal regulatory agencies have shifted the predominating scientific perspective from pharmacology back to the experimental analysis of behavior (psychology). Nowhere is this more evident than in tier I safety assessment of the central nervous system (CNS). The CNS and peripheral nervous system have multiple behavioral units of general activity. A complete picture of the motor control neural pathways cannot be measured by any one single approach. The CNS safety protocols under International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use S7A are required to be conducted in accordance with Good Laboratory Practices by trained technical staff. The CNS safety assessments necessitate the inclusion of a thorough and detailed behavioral analysis of home cage activity, the response to handling, and transportation to and observations within an open-field apparatus with ancillary measures of basal muscle tone, muscle strength, and tremor in a functional observation battery, as well as quantitative measurements of 3-dimensional activity in an automated photobeam arena. Cost-cutting initiatives or a radical application of the “reduce use” principle of the 3 Rs only jeopardize the spirit, intent, and predictive validity of tier I safety testing assays dictated by current drug safety guidelines. |
| Databáze: | OpenAIRE |
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