Document 9JVr7j5gb1qadOVzVpOGvLJpL

C K L. ICN. TON IB O h W .C N RAN ILL , yE ,.cMt t ti m B i iN T iio i n t F. W . R O C K W E L L , vie ^ iiid in t ROBERT U N D L tV Zl EG fELD SECRETARY-TfittAtuHCR 4-20 LEX IN G TO N A V EN U E N E W Y O R K 17.N.Y. June 9, 1948 MANFRED BOWDITCH DIRECTOR o r HEALTH AND SAFETY Robert A. Kehoe, M.D. Director, Kettering Laboratory College of Medicine Eden Avenue Cincinnati 19, Ohio Dear Bob: I have noted the abstract of a paper by Ryder Cholak and Kehoe on "Influence of Dithiopropanol (BAL) on Human Lead Metabolism." If reprints of this are available, I would greatly appreciate your having one sent to me. ILesitfH 'IfimcflliEisiEipflces 4 -2 0 LEX IN G TO N AV EN UE CLINTON H .CRA N E.m u id ik t K .C , * R O v * N tU ,V I M M IM N T fR OWB.E noC RT H L W IN E O L L.v LCV ici ZIE OMrcEiL. eOn i T N E W Y O R K 17,N.Y. July 8, 1948 MANFRED BOWDITCH DIRECTOR OF HEALTH AND SAFETY Robert A. Kehoe, M.D. Kettering Laboratory of Applied Physiology College of Medicine Eden Avenue Cincinnati 19, Ohio Dear Bob: Thank you for your letter of July 6. I had a hunch that I would get a reply from Cincinnati and what I got is remarkably in line with what was expected. I flatter myself that I understand what you are talking about (perhaps, as we speak of effective temperature, we should coin some such phrase as "effective toxicity";. I am in substantial agree ment with most of what you say. Quite apart, however, from the good, bad or indif ferent jobs that various industries are doing, I cannot feel that such discussion is unprofitable. In general, the con sensus of opinion seems to be that we should look forward to a differentiation in MACs such as I have suggested, but that further studies must be a preliminary. I wanted to start some thinking along these lines and have apparently done so. If you are interested, drop in when you are next in these parts and I 'll show you the rest of the correspondence. Sincerely yours, y 2- C - 7 Q. Vru. 'f'J , ' Patted. % JLkA** (L^l 03495 July 6, 19^8 Mr. Manfred Bovdltch, Lead Indus*tries Association, 42u Lexington Avenue, New lerk City 17* Dear Manfred: I am glad to comment on your letter of July 1 and its enclosures, and vhat I shall say is precisely vhat I should be prepared to eay publicly, at the meeting of Z->7 or elsewhere. First, there can oe no doubt that the practical hazards of occupa tional lead exposure vary tremendously with the chemical composition and physical state of the compound or compounds suspended in the air breathed by workman. I have never said or thought anything to the contrary. It is obvious that galena*suspended in the air in connection with mining operations, presents a quite different problem from that of the same concentration of metallic lead and/or lead oxide, distri buted in the atmosphere of a smelter or foundry. One is substantially harmless . The other in the concentration of 1.5 m g . per lo cubic meters is dangerous for prolonged periods of exposure (in excess of one to two years). This is not wholly a question of solubility, but is in part a matter of state of subdivision and shape of particle. No doubt the solubility and chemical reactivity, (i.e. nature of the chemical compound,) are Important factors of the practical hazard of lead compounds, but the physical factors, also influence the matter tremendously. * Second , when we speak of toxicity , ve must be sure whereof ve are speaking. Fairhall, with his customary difficulties of cerebration and personality, confuses the issue, not by misquoting me, but by failing to understand what either he or I is talking about. Toxicity, in the toxicological laboratory, may have meanings utterly unrelated, or only indirectly related, to practical hazard. When I spoke (correctly) of the toxicity.of tetraethyl lead, I was talking about, the letnal properties of a material chat was known to have been absorbed, and about the effects upon the functions of tissues incident to the presence, therein of a known quantity of lead. I did not under take to say vhat its final form or chemical combustion in the tissues might be. My purpose in the article cited was only tc point out that when one administers lead chloride or lead acetate (dissolved in water) intravenously, the mortality among experimental animals corresponds to that which results from.the intravenous injection of a corresponding quantity of lead as lead tetraethyl. I did not say, and in fact, did not discuss,in this relationship,' the practical industrial hazards of tetraethyl lead. Fairhall knows'full .well that I have stressed the seriousness of these hazards ,, their mechanisms, and their control. He simply cannot bring himself ever to be rational,.sensible or relevant in any matter that involves me and my doings and sayings in relation to lead. That is, of course, understandable, but it is childish and Mr. Manfred Bovditch - (2) - July 6, 1948 also dangerous. But to resume the discussion, toxicity, in relation to a cell or a collection of cells in the body, is one thing. The potential toxicity of a material outside the fcody, on the skin, in the alimentary tract or even in the respiratory tubes and air cells, is quite a different matter, ^luce any evidence of toxicity depends upon the ability of the material to gain access to the tissues. From then on vhat happens vill depend upon vhere it goes and hov it is disposed of, but, if it does not get in, it exerts no'practical threat. The general biologist knows this and has long since pointed out that there is no necessary relationship between the toxicity of a substance for unicellular organisms, and that for complex forms of animal life. I repeat, therefore,- let us know what we are talking about. Third, there are very few-sound "clinical and experimental data, in relation to the various compounds and subdivisions of compounds represented Individually or collectively in industrial environments, whereby we can aet tolerances. I and my associates have the most precise and best correlated data available on this matter, I am sure, in relation to a number of situations, but with one exception, namely, that of exposure t o .tetraethyl lead, they are not qualitatively and quantitatively adequate for the purpose. Vie regard this problem as requiring extensive investigation,, and we have .planned a program of human experimentation along.this line, comparable to.our work on the ingestion of lead. Until this is done by ourselves and/ or others on a comprehensive 3cale in the laboratory or in industry , tolerances cannot be set with much better background than now exists. Fourth, a standard not related to the environment, but tc the extent of the lead absorption,could be set up, with every assurance that it will stick indefinitely. This cannot be done in relation to stippling or to quantitative estimates of basophilic material in the blood, for these physiologic responses are not dependent primarily or solely upon lead absorption. There.is no point whatever in adding confusion to the existing confusion by promoting reliance upon any such procedure. One will have to measure by appropriate specific analytical means the extent of the absorption of lead, as shown by the lead concentration in certain body fluids. Vihen this is done, no Important consideration need be given t o the nature of the exposure or to the compound Involved. Danger, or the lack of it, can be expressed adequately in terms of the concentration of the element. In relation to both of these matters (1 .e. basophilic material in the blood, and lead concen tration in blood, -urine, etc.) the data are available to prove my statements, and therefore no serious question of fact exists. Here we return to the problem of toxicity. There can be no very serious d oubt that the extent of the risk of poisoning from Tead which has actually been absorbed into the b o d y , relates to the quantity absorbed and not to the nature of the compound to which the individual was exposed. (There may be an exception to this, but for the lower levels of prolonged absorption and accumulation in the body this statement can be accepted as valid with little or no doubt.; Thus, if ve were to resort to such a standard, ve could ignore all controversial and confusing matters related to the "toxicity", solubility, state of subdivision, of the several industrial lead compounds and devote our . Manfred Bovditch - (2; - July 6, 1948 attention to the maintenance of safe conditions for the men. Finally, I do not believe it is either practical or necessary to under take at this time to set standards vith respect to maximum allowable concentrations of various lead-containing industrial materials in the atmosphere of working establishments. Bloomfield's standard, a con siderable improvement over that of Duckering (as promulgated by LeggeJ, is largely a bench-mark - a reasonable approximation of the general situation. It relates to certain conditions and not to others. It is at once too high and too low. But It serves a useful purpose among the initiated, and hurts the csnse very little among the dogmatic and ignorant. Until we are in better position to substantiate other figures, ve had better leave It alone. Ve do not need a new standard of this kind nearly so much as ve need performance in line with the implications and the purposes of the present standard. It is certain that our knowledge is not altogether adequate, but if American Industry were to do half as veil as present knowledge would justify, ve would not be engaging in this kind of a discussion. Sincerely yours, YAK ef Robert "`A. K e h o e , M . D. 03498