Kinetics and disposition in toxicology. Example: carcinogenic risk estimate for ethylene

Pharmacokinetic analysis of the behaviour of xenobiotics in living organisms is the basis for the understanding of dose (concentration-) response relationships. Risk estimates may lead to erroneous results if pharmacokinetic principles are neglected. The pharmacokinetic behaviour of a xenobiotic should be known before planning long-term experiments on toxicity and carcinogenicity. This is demonstrated using ethylene as an example. On the basis of the pharmacokinetics in rats of ethylene and ethylene oxide, its carcinogenic metabolite, we estimated the theoretical risk for the carcinogenic potential of ethylene. Our results demonstrate that exposure of rats to ethylene concentrations higher than 1000 ppm correspond to a (theoretical) exposure to 5.6 ppm ethylene oxide: exposures to ethylene at 40 ppm are equivalent to ethylene oxide exposures of 1 ppm, which is the (new) TLV for ethylene oxide.