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Pharmacokinetic analysis of isoprene inhaled by male Wistar rats and male B6C3F1 mice showed saturation kinetics in both species. Below atmospheric concentrations of 300 ppm in rats and in mice the rate of metabolism is directly proportional to the concentration. The low accumulation of isoprene in the body at low atmospheric concentrations suggests transport limitation of the metabolism. Only small amounts of isoprene taken up are exhaled as unchanged substance (15% in rats and 25% in mice). Its half life in rats is 6.8 min and in mice 4.4 min. At concentrations above 300 ppm the rate of metabolism does not increase further in proportion to the atmospheric concentration. It finally approaches maximal values of 130 mumol/(h X kg) body weight at atmospheric concentrations above 1500 ppm in rats, and 400 mumol/(h X kg) body weight at concentrations above 2000 ppm in mice. This indicates limited production of the two possible mono-epoxides of isoprene at high concentrations. Isoprene is endogenously produced and is systemically available. Its production rate is 1.9 mumol/(h X kg) in rats, and 0.4 mumol/(h X kg) in mice, respectively. Part of the endogenous isoprene is exhaled by the animals but it is metabolized to a greater extent: the rate of metabolism of endogenously produced and systemically available isoprene is 1.6 mumol/(h X kg) (rats) and 0.3 mumol/(h X kg) (mice).
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