Grip strength test and infrared thermometry as non-invasive methods to complement acute toxicity data in mice.

Abstract

Acute toxicity testing in-vivo seeks a new approach minimising the number of animals used and increasing the number of quantitative and qualitative observations. The measurement of grip strength of mice (forelimbs), a classical tool for the evaluation of muscular force and the emitted heat measurement, as a tool for evaluation of basic metabolism, have been used. The aim of acute toxicity was, up to now, to determine LD50 level or eventually a minimal lethal dose. These non-invasive tests give an idea of general health condition and allow the determination of the minimal toxic dose while in the search for the minimal lethal dose. A computer-assisted grip strength test and an infrared thermometry test have been developed and calibrated with Na+ pentobarbital, theophylline and diazepam given once orally or intraperitoneally to 10 male NMRI (MAI) mice/dose. The tests were performed within one hour after administration and daily until the values of the surviving animals went back to normal. Dose-response curves were obtained and plotted against control animals (n = 10). Oral and intraperitoneal administration in ascending doses of Na+-pentobarbital, theophylline and diazepam (i.p. only) up to the lethal level have a parallel influence on grip strength and heat emission; the correlation with mortality is clear for Na+-pentobarbital and diazepam but not for theophylline.