Effect of equilibration zones on stability, uniformity, and homogeneity profiles of vapors and aerosols in the ADG nose-only inhalation exposure system.

A commercially available, inexpensive, nose-only exposure chamber was modified to include removable equilibration zones, and the effect of these zones on chamber performance was determined. Since limited performance data were available concerning this unit, a more extensive characterization was performed. EPA limit concentrations (greater than or equal to 5 mg/liter) of toluene vapor or corn oil aerosol, and relatively low concentrations of uranine aerosol (less than or equal to 50 micrograms/liter) were produced by standard techniques. The presence or absence of equilibration zones did not affect the stability or uniformity of toluene vapor atmospheres, with the coefficient of variation (CV) not exceeding 3.33% in all experiments. In contrast, the presence of two equilibration zones was found to progressively enhance the uniformity of the inhalable test aerosols in the animal exposure zone (CV less than or equal to 3.16%). Matrix sampling revealed that in both uranine and corn oil experiments, the center matrix point concentration was consistently lower than samples taken in the actual animal breathing zone. Equilibration zones markedly reduced the difference between breathing zone and center point concentrations. These performance data indicated that the modified ADG nose-only exposure system performed exceptionally well with the materials that were studied. Results were comparable to those describing whole-body chamber performance. The ready availability of this inexpensive prototype lends itself to standardization of techniques between laboratories.

Effect of acute and chronic cadmium treatment on hepatic drug metabolism in male rats.

The effect of acute and chronic cadmium administration on hepatic drug metabolism was investigated in the male rat. 3 days after the acute administration of cadmium by either the intraperitoneal (0.84 mg Cd/kg) or the oral (greater than 80 mg Cd/kg) route, there was a significant potentiation in duration of hexobarbital hypnosis and inhibition of hepatic microsomal metabolism of hexobarbital and aniline. Administration of cadmium in the drinking water at levels of 100 or 200 ppm Cd for periods of 2--12 weeks or at levels of 5 or 20 ppm Cd for 50 weeks did not produce alterations in either drug response or hepatitic drug metabolism. Significant levels of metallothionein, a cadmium binding protein, found in the liver of the rats receiving cadmium chronically may offer an explanation for the observed differences in drug metabolism between the acute and chronic administration of cadmium. In additional studies, pretreatment of the rats with subthreshold doses of cadmium (0.21 or 0.42 mg Cd/kg) intraperitoneally produced a tolerance to the alterations in drug metabolism induced by the previous cadmium dose (0.84 mg Cd/kg, i.p.). However, chronic cadmium treatment (5 or 20 ppm Cd for 50 weeks) did not impart any such tolerance to subsequently administered Cd (0.84 mg/kg) by the intraperitoneal route. The hepatic levels of metallothionein induced by the chronic cadmium treatment were only 30--60% of those induced by the subthreshold cadmium and thus may not have bound enough of the large challenge cadmium dose to produce the tolerance phenomenon.

The comparative effects of barbituric acid phenobarbital on blood glucose and insulin secretion in mice.

The effects of barbituric acid and phenobarbital upon carbohydrate metabolism in mice were compared. An intraperitoneal dose of 100 mg/kg of barbituric acid increased blood glucose concentrations during an intravenous glucose tolerance test, but did not alter the rate of glucose disappearance from the blood. Barbituric acid also antagonized the hypoglycemic effect of intravenously administered tolbutamide. The same dose of phenobarbital had no effect. An in vitro concentration of 100 mug/ml of barbituric acid decreased the responsiveness of isolated mouse pancreatic islets to glucose stimulation (3.0 mg/ml D-glucose). Again phenobarbital, 100 mug/ml, was without effect. The structural similarities between barbituric acid, tolbutamide and alloxan suggest that the effects observed in these experiments might reflect a competition for binding to reactive sites on or within the pancreatic B-cell.