A COMPARISON OF THE LETHAL EFFECTS OF NITRITE AND HYDROXYLAMINE IN THE MOUSE

¹ Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire

Hydroxylamine hydrochloride injected i.p. is more acutely toxic to mice than sodium nitrite injected i.p.; but when given in equal sublethal doses, the two chemicals generate equivalent peak levels of methemoglobin. Peak levels of methemoglobin are reached in 10 min or less after hydroxylamine, and animals die within the same time period. Death is delayed after nitrite and correlates in time with the more delayed peak methemoglobin formation. A nitrite-generated methemoglobinemia persists longer than a hydroxylamine-generated methemoglobinemia both in mice and in mouse erythrocyte suspensions, but the effect of methylene blue in attenuating the methemoglobinemic response is more dramatic in the case of nitrite. Hydroxylamine further differs from nitrite in that the former has a greater tendency to produce "sulfhemoglobin-like" pigments. Pretreatment of mice with methylene blue significantly protects them against death by either nitrite or hydroxylamine and significantly attenuates the methemoglobinemic response to either chemical. These effects, however, are greater in the case of nitrite than in the case of hydroxylamine. l-Arginine does not alter significantly the methemoglobinemic response to hydroxylamine, and yet it protects mice against death by hydroxylamine but not by nitrite. These results are inconsistent with the interconversion of nitrite and hydroxylamine in mice or mouse red cells.