1. The administration of sodium nitrite or para-aminopropriophenone (PAPP) to rats caused a rise in the methemoglobin level with maximum concentrations of methemoglobin occurring generally after one-half to one hour. The level of methemoglobinemia gradually declined thereafter. No significant difference was observed between intragastric and subcutaneous administration either in the time-course or in the maximum level of methemoglobinemia achieved. When adminisitered at separate sites by the subcutaneous route, sodium nitrite and para-aminopropriophenone exert an additive effect in forming methemoglobin.
2. The concentration of PAPP in propylene glycol affected appreciably the course of methemoglobinemia. More concentrated solutions of PAPP caused greater methemoglobin formation, even when the total amount given was identical.
3. The dosage response curve for PAPP and sodium nitrite in rats has been defined.
4. Limited data have been obtained on the dosage response curves of human subjects without hematologic disease after the administration of sodium nitrite and PAPP.
5. No effect of red cell age on methemoglobin content of erythrocytes could be discerned using the method of differential osmotic hemolysis.
6. Stable concentrations of methemoglobin in the blood of human subjects could be achieved by chronic administration of drug every four hours.
7. The administration of 5 mgs. PAPP/Kg. body weight to rats resulted in accelerated destruction of red cells. In contrast, the administration of propylene glycol alone or the administration of 50 mgs. sodium nitrite/Kg. body weight, a quantity inducing tile same degree of methemoglobinemia, failed to accelerate red cell destruction.