Design of a primary screen for developmental neurotoxicity.
A battery of tests was devised for routine use as a primary screen for developmental neurotoxicity. The battery was divided into preweaning and postweaning tests using rats as subjects. Since the rat CNS is structurally incomplete at birth, preweaning tests were predominantly physical, using specific landmarks of somatic maturation and regional brain growth as indices of normal development. Pupillary responses to light and positional responses to gravity (negative geotaxis) were also included in the preweaning battery to monitor reflex behavior, a relatively simple CNS function. The postweaning battery predominantly contained functional tests to evaluate higher order behaviors that develop after completion of neurogenesis. The postweaning tests were divided into 4 subsets designed to evaluate (I) neuromuscular function, (II) memory, (III) problem solving, and (IV) neuroendocrine function, respectively. Curiosity, rhythmicity, patency of monoamine neurons, and physical measures of brain growth were included within the subsets so as to evaluate a spectrum of CNS functions. Preliminary findings suggest that tests and instrumentation selected for the proposed battery provide an informative, objective, comprehensive and cost-efficient means to screen for developmental neurotoxicity.
Walker
R F
RF
Smith Kline and French Laboratories, Research and Development Division, King of Prussia, PA 19406-0939.
Guerriero
F J
FJ
Wier
P J
PJ
D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D009420:Nervous System / Q000187:drug effects*; D051381:Rats