Toxicokinetics Metabolism and Genotoxicity of Nitropropane in Rats and Mice
Interim rept. Sep 1988-Aug 1989
INSTITUT FUER TOXIKOLOGIE NEUHERBERG (GERMANY F R)
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Pharmacokinetics of atmospheric 2-nitropropane 2-NP were investigated in female and male rats at initial concentrations between 100 and 3000 ppm using closed exposure systems. A thermodynamic partition coefficient bodyair of 180 was obtained from experiments in vivo. A value of 161 was estimated from experiments in-vitro. Due to the metabolism in the animals, the actual concentration in steady state bodyair was far below these values. At concentrations below 10 ppm it was 23 and 30 in male and female rats, respectively. 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 a saturable one according to Michealis-Menten kinetics, females having a higher metabolic capacity than males. The share of the non-saturable pathway was therefore higher in males than in females and exceeded the share of the saturable pathway above 60 ppm in males and above 180 ppm in females. IP administration of 2-NP 1.y mmolkg b.w. to rats resulted in an acute hepatotoxicity indicated by an increase of liver enzymes GOT, GPT, and OCT in serum with a peak concentration after 8 h. The values in males were much higher than in females and showed a dose response curve at concentrations from 0.13 to3.4 mmolkg of 2-NP. Exposure of rats, 4-5 days old, to 2-NP 0-125 ppm for 3 weeks and subsequent treatment with Clophen A50 resulted in the formation of ATPase-deficient preneoplastic foci.