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

Abstract

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

Repositioning VU‐0365114 as a novel microtubule‐destabilizing agent for treating cancer and overcoming drug resistance

“…To assess any potential neurological effects of VU‐0365114 in mice, a functional observation battery (FOB) test was performed before and after administering VU‐0365114 treatment. The FOB test involves observing and recording various behaviors and physical conditions to assess overall health, neurological function, and treatment effects [ 21 ]. As shown in Table S4 , VU‐0365114 did not alter the FOB parameters, suggesting the absence of neurological toxicity.…”

“…Six‐week‐old male BALB/C mice (Trineo Biotechnology) were intraperitoneally injected with 5 daily doses of VU‐0365114 (5 mg·kg −1 ; n = 3) or the vehicle solvent control (4% DMSO in PBS; n = 3) for 3 weeks. Neurotoxicity was assessed using the functional observational battery (FOB) [ 21 ], both before and after administering VU‐0365114 treatment. The FOB encompassed a comprehensive evaluation of the animals' physical appearance, behavior, and overall functional condition, following guidelines set by the United States Environmental Protection Agency (US‐EPA) [ 22 ].…”

A Systematic Assessment of Robustness in CNS Safety Pharmacology

“…In this context, it would be of future interest to conduct a multicenter study with compounds that exert more pronounced effects on autonomic nervous system function or that cause sedation. Despite earlier efforts to assess the variability in Irwin/FOB scoring and to identify influencing factors (14,16,24,29), this is the first study to our knowledge investigating the effects of stepby-step harmonization on neuropharmacological safety assessment in laboratory mice. In this context, it should be noted that it is impossible to achieve a state of full harmonization in experimental preclinical animal studies on a multinational level.…”

“…; https://doi.org/10.1101/2024.03. 21.586096 doi: bioRxiv preprint and mini-pigs [ (15)(16)(17)(18)(19)(20)(21)], expanding its scope of application. Irwin and other FOBs are primarily used for safety assessment in CNS drug development, providing information for decisionmaking, candidate selection, or the need for more in-depth analysis of selected potential adverse effects (22).…”

“…To allow comparability with two other subprojects of the EQIPD consortium that focused on an open field paradigm (11) and pharmaco-EEG, the study was performed in mice, representing the second most common species for Irwin/FOB testing (16,24). MK-801 was chosen as the compound, considering its broad range of effects on various parameters from different functional domains assessed in the Irwin test.…”