Planning of experiments for the testing of chronic toxicity in rats taking into account biorhythms

During the course of testing chronic toxicity in rats several physiological and biochemical parameters were investigated. Many of the processes studied show a circadian and infradian rhythm, which can clearly be influenced from the second year onwards by age dependent alterations. The daily rhythm of the following processes were investigated: Hexobarbital sleeping time, aminophenazone demethylation, Hb (Hemoglobin), Hc (Hematocrit), GPT (Glutamate-pyruvate-transaminase) and total plasma proteins. The seasonal changes of total plasma proteins, Hexobarbital sleeping time and aniline hydroxylation were also examined. The results obtained indicate, that for comparison and interpretation of data on acute and chronic toxicity the knowledge of daily and seasonal changes is necessary and has to be considered for an exact planning of experiments.