Abstract
Subchronic testing of laboratory animals in accordance with present regulatory guidelines involves maximum exposure with the chemical under investigation and serves for the evaluation of systemic toxicity as well as of lesions in organs and organ systems, including neurotoxicity. The primary assessment of neurotoxicity is essentially based on the overall observation of animal behaviour in the course of the customary toxicity studies and on the subsequent neuropathological evaluation with contemporary techniques. Under this maximum exposure the absence of symptoms and signs of neural abnormalities indicates that the material testd would be devoid of neurotoxicity.
Any overt or suspicious symptoms for neurotoxicity appearing in the course of subchronic testing may be further characterized with additional functional tests such as neurological examination, electrodiagnostics and possibly with specific behavioural tests. The subsequent neuropathological investigation would have to be expanded to include a detailed evaluation of all neural structures possibly related with the above functional derangements.
In case of relevant neurotoxicity subsequent specific behavioural tests might include the evaluation of complex neural functions such as integrated psycho-neuro-motor activity and memory. These behavioural tests might help to explain neurotoxicity and to assess behaviour at low levels of exposure. The implementation of such specific behavioural testing procedures beyond the scope of routine toxicity studies would require a group of investigators capable to earry out appropriate tests. The introduction of such testing will therefore have to be evaluated competitively regarding costs versus the advantages offered by the refinement of the other testing procedures for neurotoxicity including the neuropathological techniques. The performance of behavioural tests without preceding or concomitant toxicological evaluation is not considered to be a feasible approach.
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Schaeppi, U., Hess, R. What can specific behavioural testing procedures contribute to the assessment of neurotoxicity in laboratory animals?. Agents and Actions 14, 131–138 (1984). https://doi.org/10.1007/BF01966846
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DOI: https://doi.org/10.1007/BF01966846