Document MJ50DJyGjMYVR24O5q05rBvjV

October 31, 1929 Dr. Graham Edgar, Ethyl Gasoline Laboratory, 320 Yonkers Street, Yonkers, H. Y. fly dear Edgar: Replying to your letter of October 16 in regard to the toxicity of anilin and substitution compounds. I have gone over all the material I have on the subject, including the article to which you refer in the Journal of Pharmacology and Experimental Therapeutics The latter does not give data on the relative toxicity of these compounds, but is simply a pharmacologic study of the mechanism of intoxication shown by compounds of this sort. It points out that a considerable a, mount of the previous information on the subject is very faulty, and indicates that the intoxication is probably not due to the formation of methaemog1obin but is due rather to ` circulatory failure plus some blood destruction due to the presence of para-aminophenol* - The information which Is contained in Hender son and naggerts book is substantially that available on the subject in literature Much of it is a direct quotation ' of Alice Hamilton*s book on Industrial Poisoning in the United States. What Is said apout the relationship of toxicity to chemical structure is practically a duplication of the state ments of Alice Hamilton in her book. This has been gleaned from scattered points of information contained in a number of studies by German investigators. It is probably substan tially true, but I should not be too sanguine about the di rect relationships of toxicity to structure In and of itself. The factors of solubility and stability in the tissues are very likely to be much more important. However, from the literature there is available, there is no doubt that toludine* methylanilln and- dimeihylanilin are somewhat less toxic than anilin alone. There: Is apparently no wide difference in the toxicity of these three* Whether there is sufficient dif ference to be of any practical importance in such a problem as w@ have to consider, is another matter. I should suspect that the differences, are not great enough to be of much im portance in practical uqe. All of them work in substanti ally the same fashion and none of them seem to produce very striking phrenic effectf* However, I have not been able to find enough information in the literature to be of much help to me in arriving pi definite conclusions on this latter problem, that is that of chronic poisoning* Such information Dr. Edgar -2 as I have been able to obtain at the DuPont plant, which Is the result of a number of years* experiences, indicates that there are no important chronic effects Their experience# however, verifies the data in Henderson*s book, which I think is taken from Xobert*s work, that nitro-benzene is many times as toxic as anilin.; In general# it seems to be quite certain that a nltro group renders a compound much more toxic than an; amino or amido group; also' the toxicity increases, though not in direct proportion with the increase in the number of nitro groups The toxicity of anilin-as given by Henderson corresponds very satisfactorily with that given by Hobart# /ho quotes the experimental work of Lehman . : . In regard to your vaccine, 1 have spoken to Dr Dorst today. Ke tells me,that you should be able'-to notice some difference if you have continued the use of the vaccine for about a month He advises the continuance of the vaccine in the manner which he previously prescribed.. I reminded him that he had not'sent you a. bill# and sug~- gested that you would feel very much better about it if he would send you one* He is-notoriously slow in tending to matters of this sort# so that-1 should not trouble'about it if I were you*; You will probably receive a bill even fcually*j 1 v '' ' One thing this vaccine should.do whether it accomplishes anything els or not# is to make you less susceptible to re*infeetions from organisms of the type that go to make up the vaccine If; it does, no more than this, X believe it will give you considerable benefit# though it is, of course difficult to prove the value of preventive measures# It is always possible to conclude that the thing whleh you ar attempting to prevent might not have happened anyhow* f There is very good experiment ,tal evidence# however, that vaccines. are effective In this way*'.- -'- : With kindest personal regards* Very truly yours# RAKiEJ