Document ExnV5X5eoZeKgQDzJD2O5DDXN

July 16,..1959 Lawrence A. Gerlach, M.D. E. I* du Pont De Nemours and Company Incorporated Antioch Works California Dear Doctor Geriachs I am sending you a reprint of the article of Bambach and Burke.y, in which the "improved" procedure ,(a modification of Hubbard*s method) of the- 'dithizone -method,'- essentially-.' a s / we now use it,is described. Included with this is a further article by Cholak, Hubbard and Burkey, in which-another sig- nifleant improvement is described, There is also a typed out statement of the modifications,dated 5/18/58* With these at hand your analyst will be able to follow"the procedure pre cisely, if he so desires. : The- methods applicable to various materials were put together by Cholak and the procedures of sampling and the like were discussed by myself, in -the- booklet '.issued by the American Public Health Association.in 1955* I send a copy of this, for suck use as it may be to you. ; Please accept my thanks for the analytical data which youforwarded to me. In going over these, I am impressed by the apparent fact that your results tend to run higher than ours. Since there is no direct comparison of results obtained on equivalent samples, the appearances may be deceptive, but it was just such a possible variable as this that caused me to Insist upon having the analytical work done here. Our prior data on men in the occupations under investigation constitute the all-important base-line for these analytical findings, and I simply could not accept the intervention of a technical variable. No two laboratories obtain identical results for a variety of reasons, end this factor, which could be avoided so easily, might have made a great deal of difiference. In answer to your question concerning the concentration of lead in samples of urine of small volume, I think it wise to say that I have never approved of the use of a correction to reduce all results to the same specific gravity, This is a part of the same problem, and I can cover both aspects of the matter in the same answer. There is no doubt, as we showed many years ago, that the volume ( Lawrence A, Gerlach,, M,D, - 2- July 16. 1959 of water put through the body in unit time I . e , , t h e rate of throughput - is an important factor in the concentration of lead (and many other substances) in the urine. It is not, however, the only variable, and there are times at which it ic not the most important variable. These facts can be seen readily by the examination of the data on our experimental subjects who either ingested or inhaled known quantities of lead over long periods of time. Moreover, in following large numbers of men in a considerable number and variety of lead trades over the past twenty years, we have noted (l) that samples of urine of small volume are hot representative of the individual general excretory performance! (2) that the smaller in volume they are, the less representative they arej and (3) that the two sets of samples that deviate most from tho normal or average performance of the individual - namely, those that are very dilute and much too low in their lead content, and those that are very concentrated and are much too high in their lead content - are the least capable of being interpreted> It is actually foolhardy to draw any conclusion at 'all from them. The observations must simply be repeated under more favorable conditions. The application of a correction factor to them is not only foolish,physiologically but dangerous and irresponsible,clinically, for it is not quanti tatively correct. In general, I prefer to disregard the results of the ana?i.ysis of samples' under 50`ml,, and I do net trust the "normality" of a sample of urine that is provided at a single voiding unless it is of the drder of 100 milliliters. In dealing with inorganic lead, I rely mainly upon the lead concentration in the blood for clinical purposes. That is why X wanted these results on the bipod of the men involved in the current tests. Unfortunately, the concentration of lead in the blood is not a sound indicator of the extent of the absorption of tetraethyl lead, and therefore one must rely upon the analysis of the urine in relation to exposure to, and absorption cf, tetraethyl lead. In the present tests we are concerned with both types of lead compounds, and so I wanted both sets of results, I d i d n 't need many results on the blood, for the reasons that the variability of the blood level, from any other cause than that of an increase or decrease in the lead in the body, is so slight that one determination of the blood lead is equivalent, in the statistical sense, to several determinations of the urinary lead. Moreover, there..is. .a time lag in the change in the level of lead concentratiorf'as^ex-* posure to lead is incurred and as absorption (and accumulation) ensue, so that one confidently expects the change to occur in the urine before it occurs in the blood. In effect, the best means of detecting promptly a change in the current rate of e absorption is that of determining the rate of lead excretion j-n the urine, while the best means of estimating the general in the total lead content of the body (skeleton and soft p-is'* too) Is that of determining the lead content of the blood, Lawrence A. Gerlach. M . D . -5- July 16. i q r q far as samples'of urine are concerned, considering the physiological variability of the renal excretion of lead, one mut do either one of two things, or both, if he Is to establish a quantitative relationship between the rate of lead absorption and the rate of lead excretion; namely, he must either obtain a sample of urine of large volume by collecting it over a representative period of hours, or he must obtain quite a number of samples at intervals over a representative period of h o urs. In the first instance the vagaries of the urinary excretion will be averaged out in the one sample (for this reason we continue to,collect1samples - of large volume from a representative group of men engaged In the manufacture of tetraethyl lead); In the second instance ithe -average ..of '"several analytical results fulfills, the saiae purpose, In the first Instance, judgment must be exercised as to the length of time required, while In the. . ether one's augment i s 'concerned with' the number of samples icquiretl. In the latter 'instance,>it Is possible to discard certain samples, vihicii, because of their very nature, are undesirable. Contaminated samples are misleading and distort tnc- average; these can often be detected by their extraordin arily high content of lead. Samples of minute volume, also, are unsatisfactory, by their very nature, for the reason that they cover either too little time or are associated with y abnormal stress . : : I had not intended to write at such length, but the physio logical principles involved in any such Investigation as this, simple though it may be, need to be fully understood as a prelude to the interpretation or.statistical' manipulation of the data. : .f ; . V I trust that I have answered your question, even if I may appear tc have taken a roundabout course. Cordially yours, RAKiss Enclosures . Robert A. Kehoe, M. D. . i ' ' '