PT  - JOURNAL ARTICLE
AU  - LEONARD KAREL
AU  - RAYMOND E. WESTON
TI  - THE PROPHYLACTIC EFFECT OF HEXAMETHYLENETETRAMINE IN DOGS EXPOSED TO HIGH CONCENTRATIONS OF PHOSGENE
DP  - 1946 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 254--259
VI  - 88
IP  - 3
4099  - http://jpet.aspetjournals.org/content/88/3/254.short
4100  - http://jpet.aspetjournals.org/content/88/3/254.full
SO  - J Pharmacol Exp Ther1946 Nov 01; 88
AB  - 1. The prophylactic effect of hexamethylenetetramine (HMT), intravenously administered as a 40% solution in saline, was tested in normal, unanesthetized dogs exposed to several concentrations of phosgene by the dynamic chamber or the dosimetric technique. 2. Nine of ten dogs which received 2.0 grams of HMT/kg. of body weight 1 to 1½ hours before dosimetric exposure survived 2.43 to 7.39 mg./kg. doses of phosgene. (The LD99.5+ of phosgene for dogs similarly exposed to approximately the same concentration, 6.72 mg./l., is 2.50 mg./kgm.) Statistically, the reduction in mortality in the treated animals is highly significant. 3. Ten of eleven dogs which received 2 grams./kg. doses of HMT about one hour before 5.9 minute exposures to an average phosgene concentration of 7.98 mg./l. (mean Ct = 47,000 γ-min./l.) in a dynamic chamber survived. Five of five untreated controls died. 4. Four of six dogs which were injected with 0.5 grams/kg. doses of HMT 10-53 minutes before exposure to a phosgene concentration of 3.89 mg./l. for 6 minutes (mean Ct = 23,300 γ-min./l.) survived; 13 controls died in less than 18 hours. 5. After receiving 0.25 grams/kg. doses of HMT 60-70 minutes before exposure, 5 of 12 dogs survived a 6 minute exposure to 3.63 mg./l. of phosgene (mean Ct = 21,800 γ-min./l.) which killed all untreated animals; and 9 of 13 dogs survived a 6 minute exposure to 2.49 mg./l. of phosgene (mean Ct = 16,200 γ-min./l.) which killed 2 of 3 controls. 6. As the HMT dose was decreased, its prophylactic effect against phosgene poisoning diminished; however, at each HMT dosage the difference between the mortality of treated animals versus controls is statistically highly significant. The increase in mortality with decrease in HMT dose is suggestive of a quantitative relationship between the effective prophylactic dose of HMT and the concentration and dose of phosgene to which the animal is exposed. 1946 by The American Society for Pharmacology and Experimental Therapeutics