Effect of Vehicles on the Functional Observational Battery by Oral Gavage Administration in Wistar Rats and Need for Historical Control Data

Abstract

The effects of vehicles play a pivotal role in defining the conclusion of any regulatory and pre-clinical toxicology study. The functional observational battery is one of the vital parameters to study the toxicological effect of compounds. This study investigates the impact of oral dosing with reverse osmosis water, 0.5 % w/v carboxymethyl cellulose and corn oil on functional observational battery parameters (neurobehavioural observations, motor activity, sensory reactivity measurements, grip strength and foot splay) in Wistar rats when administered for 90 d through oral gavage. Functional observational battery was performed during the 12th w of treatment. No mortality, morbidity or clinical sign of toxicity was observed. Body weight decreased marginally in carboxymethyl cellulose treated group during the 12th w. Motor activity was increased significantly in reverse osmosis water and carboxymethyl cellulose treated groups. The decrease in foot splay was also noted in all vehicles treated groups. The variation observed in grip strength by vehicles was not definitive or conclusive. No abnormality was observed in qualitative parameters of functional observation battery (sensory reactivity and neurobehavioral observations) and gross examination. From these results, it is evident that all vehicles have some notable influence on functional observation battery performed at the 12th w of treatment. This type of variation is critical to figure out sought conclusion for the compound of interest in regulatory studies. The recommendation is given to use strong and reliable historical control data to optimise or fix these variations and to avoid false conclusion regarding the compound where these vehicles are used as a control in regulatory toxicological studies.