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; (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 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 of 0.1–0.125 gm./kg.
We have prepared from the non-saponifiable matter of wheat germ oil thress aflophanates:
1. M.p. 250°. This is a possibly the allophante of β-amyrin. The alcohol regenrated from the allopohante has no vitamin E potency.
2. M.p. 138°, readily crystallizing in long needles. The analysis agree with values required by monollophantes of an alcohol, C39H50O2. The alcohol from this allophante apparenelly has some vitamin E potency, but less than that from the third allophanate.
3. M.p. 158-160°. From this allophanate, the alcohol—for which we propose the name α-tocopherol—when given in a single dose of 3 mg. always enables vitamin E-deficient rats to bear young. α-Tocopherol shows a characteristic absoption band at 2980 A., E1 per cent1 cm. = 90 ca. Treatment with methyl alcoholic silver nitrate converts it to a substance which has absorption bands at 2710 and 2620 A respectively, E1 per centcm. = 480 ca., and possesses and some vitamin E activity.
α-Tocopherol yields a crystaline p-nitrophenylurethane melting at 120-131°. Analyses of both the urethane and the allophanate indicate a provisional formula for α-tocopherol of C29H50O2
