Comments on the assessment of neurotoxicity in routine toxicity studies.

Neurotoxicity occurs during administration of high doses of compounds, in testing for acute toxicity (LD50) or on occasion of subchronic treatment for assessment of organ toxicity. Neurotoxicity induces behavioral disturbances, usually first noticed by the animal caretakers, who are observing daily the animals tested according to authorized guidelines. During the following neurological examination a few of the exposed animals, exhibiting distinct behavioral disturbances, are compared with controls. The neurological examination serves to characterize the observed changes, while the observation of the whole group of animals in the home cages gives indications about the highest non-toxic dose level. Further tests for additional clarification of neurotoxicity would be evaluation of neuromotor spontaneous activity in the photocell-cage, behavior in the maze or operant behavior, measurement of the maximum nerve conduction velocity or other especially developed tests.