Acute Toxicity of Ethyl Chaulmoograte. ∗

Abstract

At the suggestion of Dr. H. W. Wade we studied the toxicity in rats of single subcutaneous doses of a number of representative types of ethyl esters of the fatty acids of chaulmoogra oil. Preparations included were: (1) a purified ethyl chaulmoograte supplied by Dr. R. Wrenshall, fractionated by redistillation in vacuo at 10 mm. Hg., containing a small amount of ethyl hydnocarpate as indicated by the iodine number; (2) mixed ethyl esters of fatty acids of Hydnocarpus wightiana oil prepared at Culion, containing more than 80% ethyl chaulmoograte as indicated by polariscopic measurements; (3) a similar preparation containing 0.5% iodine, prepared by Cole's method 1 ; (4) crude ethyl chaulmoograte containing 4% creosote, a preparation used in India, supplied by Dr. E. Muir from clinical supplies at Calcutta; and (5) “Chaulmestrol” (Winthrop), a proprietary preparation of mixed ethyl esters of fatty acids of chaulmoogra oil. The pertinent findings summarized in Table I agree with Martins' report 2 of 40 cc./kg. as being lethal for Leptodactylus ocelatus.

Examination of the tabulated data indicate that: (1) purified ethyl chaulmoograte preparations are more toxic than the ethyl esters of the total fatty acids of chaulmoogra oil, presumably because of higher content of ethyl chaulmoograte; (2) iodizing ethyl chaulmoograte with 0.5% iodine has little effect on toxicity; (3) addition of 4% creosote increases the toxicity, commensurate with the amount of creosote present; (4) the degree of unsaturation of crude ethyl chaulmoograte is not a sufficiently sensitive index of toxicity to be reliable; and (5) if subcutaneously administered ethyl chaulmoograte exerts its toxic effect through liberation of Na chaulmoograte into the circulation, the summation of rates of hydrolysis and diffusion cannot much exceed that causing a disappearance of 2 millimols per Mol of the injected ester per hour, since Na chaulmoograte kills rats in intravenous acute doses 3 of 0.1–0.125 gm./kg.