Chronotoxicology of florfenicol

Sixty 3-month-old homozygote male mice were studied for circadian rhythmici ty in the toxicity of florfenicol overdose. Animals were kept under a regim en of 12h light, 12h darkness (12:12 LD) with food and water available ad l ibitum. The LDS, (median lethal) dose was determined in a preliminary exper iment and was administered to groups of 10 mice at six different clock time s (hours) after light onset (HALO): 0, 4, 8, 12, 16, and 20 HALO. Cosinor a nalysis verified a statistically significant (P < .04) circadian rhythm in the toxic effect (mortality) of florfenicol. Mortality was greatest when th e drug was injected 4h after the commencement of the activity span (16 HALO ) and least when injected 4h after the start of the diurnal rest span (4 HA LO). Mortality was 2.5 times greater when drug injection was given at 16 HA LO than at 4 HALO.