The Absorption of Monomethylhydrazine through Canine Skin ∗

Abstract

Summary

Graded doses of monomethylhydrazine (MMH) were applied to a 300-cm² area of the shaved chest of anesthetized dogs. The area of skin to which the MMH was applied was reddened within 5 min, and the color progressively changed to deep red, then to yellow-brown to dark purple and, after 6 hr, to light gray. The area of application swelled markedly within 10-20 min. Swelling persisted for 3 hr, then gradually decreased and disappeared by 6 hr. MMH was detectable in the blood within 30 sec after the initial application. With doses less than 3 mmoles/kg, blood MMH levels rose to a peak in approximately 1 hr, and decreased slowly during the next 5 hr. As size of dose increased, higher peak levels of blood MMH were reached and the rate of subsequent decline decreased until, with doses of 4-6 mmoles/kg, no decline was seen during the 6-hr period of observation. Within 3-5 min after application of large doses of MMH to the skin, methemoglobinemia was observed. Levels of methemoglobin rose to a peak at about 2 hr, then declined slowly. Peak levels varied directly with the dose of MMH applied, and blood levels of methemoglobin and of MMH were closely correlated throughout the observation period. Peak methemoglobin levels were approximately 1/5 of peak levels seen after iv injection of equal doses. The absence of a decline in blood MMH levels after large doses was attributed to effects of MMH on metabolic systems of detoxication and/or excretion.