International validation of a neurobehavioral screening battery: the IPCS/WHO collaborative study

A neurobehavioral screening battery consisting of a functional observational battery (FOB) and an automated measure of motor activity is the subject of an international collaborative study. Eight laboratories (four in Europe, four in the U.S.) are participating in this study, which is sponsored by the International Programme on Chemical Safety within the World Health Organization. Representatives from each laboratory received training on testing procedures and the study protocol during a 2-day workshop. Each laboratory then conducted studies using positive control chemicals to demonstrate their proficiency with the techniques. For motor activity studies, each laboratory had to show acute increases and decreases in activity produced by triadimefon and chlorpromazine, respectively. Using the FOB, each laboratory had to detect certain neurological syndromes: tremorigenic activity of a single dose of p,p'-DDT, cholinergic signs with parathion, and neuromuscular deficits with short-term (1-2 weeks) repeated administration of acrylamide. In the formal studies, the effects of seven chemicals are currently being determined following both acute and 4-week exposures. The chemicals include triethyl tin, acrylamide, parathion, p,p'-DDT, toluene, lead acetate, and N,N'-methylene bisacrylamide. All chemicals were provided to the laboratories from a single supplier. Each laboratory is conducting the studies under their standard conditions, using their own strain of rat and testing equipment. Each laboratory also determines a maximum-tolerated dose for each compound as well as the time of peak effect following acute exposure. A simple algorithm is then used to select doses for the formal acute and repeated-exposure experiments. These studies will provide information regarding the reliability and robustness of neurobehavioral screening methods over a wide range of laboratory conditions.