Extrapulmonary effects of NO2 as reflected by pentobarbital-induced sleeping time in mice

The influence of nitrogen dioxide (NO2) on pentobarbital (PEN)-induced sleeping time (S.T.) was investigated in mice. Acute exposure to concentractions as low as 470 microgram NO2/m3 (0.25 ppm) caused a significant increase in PEN-induced S.T. No significant effects on PEN-induced S.T. were detected after 1 or 2 days (3 h/day) exposure to 235 microgram NO2/m3 (0.125 ppm). None of the exposure regimens affected the time required for the drug to induce sleep. When the effects of repeated daily exposures (3 h/day) to 9400 microgram NO2/m3 (5 ppm) were compared in male and female mice, the females had a significantly increased PEN-induced S.T. after 1 and 2 days of exposure. However, an increase in PEN-induced S.T. was not observed in males until the 3rd day of exposure. Since the duration of PEN-induced S.T. is primarily determined by hepatic mixed function oxidase activity, it is possible that NO2 may alter some aspects of xenobiotic metabolism.