SIMPLE NEUROBEHAVIORAL FUNCTIONAL OBSERVATIONAL BATTERY AND OBJECTIVEGAIT ANALYSIS VALIDATION BY THE USE OF ACRYLAMIDE AND METHANOL WITH ABUILT-IN RECOVERY PERIOD

A functional observational battery (FOE) with modified objective gait analysis was validated using the neurotoxicants acrylamide and methano l. The FOE consisted of side cage observation (30 sec); open field obs ervation (2 min); evaluation of handling, reflexes, and gait scoring; and grip strength of the fore limbs and hind limbs. Temperature and bo dy weight were measured. Gait analysis was based on measurements of th e distances and angles between sequential foot strides after walking i n a corridor (90 x 10 x 10 cm). Landing foot splay was the distance be tween the inner surfaces of the fourth digits of each foot after the a nimals were dropped from a 30-cm height. Acrylamide was given at doses of 0 (saline), 20, and 40 mg/kg intraperitoneally. Days of dosing wer e 1, 3, 5, 7, 9, 11, 13, 15, 17, and 19. Evaluations were done before dosing on Days 0, 2, 5, 11, 17, and 27 (for recovery). Methanol was gi ven to another group at doses of 0 (distilled water), 3.25 (escalated to 8.5 before end of evaluation), and 6.5 ml/kg. Days of dosing were 3 , 5, 7, and 10; evaluations were conducted at 0, 6, 8, and 12 days. Ac rylamide at 40 mg/kg demonstrated a biologically significant increase in foot splay in males on Days 3 and 17 and was not recovered by Day 2 7. A significant decrease in the hind limb grip strength was seen in h igh-dose females, but with incomplete recovery on Day 27. Methanol (3. 25/8.5 ml/kg) induced a biological decrease of activity postdosing on Days 6, 8, and 12. A significant increase in gait length was seen in f emales only at the 6.5 ml/kg dose at Day 12. Selected doses and schedu le of observation validated the battery for screening and better quant ification of acute and chronic neurotoxicity. (C) 1997 Academic Press.