Rodent population variation

In risk characterization, step four, the human exposure situation is compared to the toxicity data from animal studies, and often a safety -margin approach is utilized. The safety margin is based on a knowledge of uncertainties and individual variation in sensitivity of animals and humans to the effects of chemical compounds. Usually one assumes that humans are more sensitive than experimental animals to the effects of chemicals. For this reason, a safety margin is often used. This margin contains two factors, differences in biotransformation within a species (human), usually 10, and differences in the sensitivity between species (e.g., rat vs. human), usually also 10. The safety factor which takes into consideration interindividual differences within the human population predominately indicates differences in biotransformation, but sensitivity to effects of chemicals is also taken into consideration (e.g., safety faaor of 4 for biotransformation and 2.5 for sensitivity 4 x 2.5 = 10). For example, if the lowest dose that does not cause any toxicity to rodents, rats, or mice, i.e., the no-ob-servable-adverse-effect level (NOAEL) is 100 mg/kg, this dose is divided by the safety factor of 100. The safe dose level for humans would be then 1 mg/kg. Occasionally, a NOAEL is not found, and one has to use the lowest-observable-adverse-effect level (LOAEL) in safety assessment. In this situation, often an additional un-... 

Isoenzymes for activity. Depending upon the species and organ, as many as seven P-450 Isoenzymes have been reported. P-450 Isoenzymes are under genetic control In both man and animals. Using the antihypertensive drug debrlsoqulne, Smith and his colleagues have studied the genetic variations of several human populations and several species of rodents and strains of rats. 

Data obtained in rodent studies are generally presented as lymphocyte subset percentage, absolute numbers (or normalized if lymphoid tissue is assessed), and CD4 CD8 T cell ratio. Typically, results are expressed as percent change between the mean value of drug-treated animals and the mean value of vehicle control animals, and statistical analyses are conducted to evaluate significance of the changes. For non-rodent species, it is important to look at the changes in lymphocyte populations from baseline, since there is often variation both within an individual animal and between individual animals. 

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