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Toxicokinetics, Metabolism, and Genotoxicity of Nitropropanes in Rats and Mice
Final rept. 1 Sep 1988-31 Mar 1991
INSTITUT FUER TOXIKOLOGIE NEUHERBERG (GERMANY F R)
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Toxicokinetics of atmospheric 2-nitropropane 2-NP were investigated in rats and rabbits of both sexes. A thermodynamic partition coefficient body air of 170-180 was obtained in both sexes and species from the data obtained in vivo. A similar value of 161 was calculated from the in-vitro accumulation of atmospheric 2-NP in water and olive oil. Due to metabolism in the animals, the actual concentration at steady state bodyair was less than the former values, declining to 22-30 at concentrations below 10 ppm. 2-NP was found to be metabolized via two pathways, a non-saturable one according to first-order kinetics, which was quite similar in both sexes and species, and a saturable one according to Michealis-Menten kinetics. In rabbits no sex difference was found, and the capacity per kg body weight was similar to that of female rats. The amount metabolized by the non-saturable pathway was higher in male than in female rats and exceeded the share of the saturable pathway in males already above 2-NP concentrations of 60 ppm, in females above 180 ppm. In rabbits the respective value was reached only at 300 ppm. 2-Nitropropane, Sprague-Dawley rat, New Zealand White rabbit, Inhalation toxicokinetics, Accumulation, Metabolism, Hepatotoxicity, Liver foci bioassay, Carcinogenicity, Software dev.
APPROVED FOR PUBLIC RELEASE