Dermal dose, excretion differences

Because these experiments illustrate the excretion differences between dermal. Intramuscular, and oral dose excretion, the excretion differences between compounds, and also problems about which urinary metabolite to monitor (see 44). a very comprehensive experimental design would be necessary to correctly model dermal exposure, absorption, and urinary metabolite levels. Statistical problems, centering around replicate variation and the resulting necessity for abnormally large numbers of replications, could drive the costs of such an experiment In small animals, and certainly in humans, to prohibitively high levels. 

Unresolved Issues Include how many samples of each are required and how can one relate dose to absorption, excretion to AAChE, or (of academic Interest) dose to excretion. The difficulty in correlating dermal dose and excretion (2,26,27) is related in part to the differences mentioned earlier between measuring dose with pads-and-gloves and washing the skin (2,18). The correlation difficulty is most severe with the skin wash technique because it measures the dose that isn t absorbed. Depending upon the time-history of exposure and the kinetics of absorption, it should be equally expected that dermal dose by washing and urinary excretion will even... 

There are limited data on the excretion of chlorobenzene. In humans exposed via the inhalation and oral routes, chlorobenzene and its metabolites were detected in urine and there were differences in excretion patterns via the two routes. Chlorobenzene and its metabolites were also detected in exhaled air of rats following inhalation and in exhaled air and urine in rabbits after oral exposure. The urinary metabolite profile appeared to be dose dependent and there were changes in excretion patterns due to multiple versus single exposures. No data on excretion following dermal exposure are available. Additional studies would be useful in determining the significance of these differences with regard to risk associated with different routes of exposure. 

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