Document 1deYYVZDZO8mXmy30706Mkyj

July 12# 1 955 Dr* Graham Edgar Ethyl Gasoline Corporation Chrysler Building Hew `fork City Hew `fork . % dear Edgars I have your letter of July 10th and I can understand your uncertainty about the present situation of normal urinary lead* I do not think the situation is as bad or as unexplainable as it seems to you* however* and therefore I want to point out to you a feit points that must be taken into account * 4J4* During the period of years In which we have been studying this question we have learned many things about the collection of samples* We now send out detailed Instructions with every container* and the evidence is quite adequate to show that we receive better samples* There are fewer gross contaminations and the mean results are therefore lower* 124- Our analytical procedures have been modified from time to time to give greater precision# and with the development and standardisation of our specferographic method w@ are obtaining analytical results which are without doubt more accurate than those obtained in previous years* I small part of the improvement occurred with the removal from ohr former laboratory to the present one* This change meant better and cleaner space* better .storage facilities for samples# better distilled water* and better general chemical technique XJsX We have also learned mush as to the variation in the lead excretion of individuals for purely physiological reasons* Thus the following factors measurably influence the rat of excretion In the urine* , (h) The quantity of food eaten influences the quantity of lead ingestion and also the extent of absorption# upon which urinary xoretlon depends (b) The water metabolism influences the quantity and concentration of lead in the urine* Thus the quantity of lead output in the urine in the winter is greater than in the summer but in winter the concentration is lower* ->r. 2 (o) Physical activity increases the urinary lead output* Hen working hard, and in hob weather, will show a considerably higher urinary lead concentration* There la even a difference between the lead content o f tho urine in the daytime, as compared to the night, the latter giving a lower lead concentration* How all of these factors have played their parti In the picture which we now have* The medical students referred to in the T.iWM*A were relatively sedentary, and all th samples were obtained.in cold weather* W obtained very large samples and it is possible that some of these were obtained after drinking excessive amounts of water, although this was discouraged in the Instructions* These factors favored a low urinary concentration* Other normal subjects studied during the same general period as these medical students (i.e* within that year), gave slightly higher 'mean results* Thus one of our subjects showed a mean of 0*055 a sanies of samples obtained during hob weather# Xou se therefore that physiological variation is not without significance*' (ix) How for Just one other point* The discrepancy between our earlier figures, and the more recent ones is not as great as it seems from your statement that the "average of DX2 by the chemical method4* is only about "onefifth of the former results" in the same article in which the figure of 0*012 for medical students is given normal mean values on other subjects are recorded as high as 0*029 + 0*002 by the chemical method* This is almost half th former mean of 0*07* I must take exception, too, to your us of the word "average" as applied to ''mean41* It. seems a small point but actually it is quite important for th simple reason that occasional high results mak little difference in an "average" but they are much more heavily weighted in the calculation of a mean* Thus when you recognise that th difference between cur former moan of 0*0? and bur present one, which would certainly'-come to 0*025, is only 0*.0l+5# it is not very great either chemically or statistically* For example, the average of the means obtained bn the ten subjects studied by the continuous laboratory method (p*3 of the reprint from the J*A*MA*) is 0*021 * 0*002* Com paring this with the mean value for medicaid'students given on p.283 of th article "On the Normal Absorption and Excretion of Lead, II Lead Absorption and Lead Excretion in Modern America! Life", the difference is 0*01{j6 + 0*005i{.* This difference is significant statistically,""of coijrsa, but it; is actually only 8 times its own probable error* It must be at least l,*. times its own probable error to be regarded as beyond the range of purely chanc biological variation* Thus, you may see that we are still dealing with figures of the s*_:i order of magnitude both chemically and biologically* He 00154S1 >raham Edgar 3 Thera is no real question as bo the accuracy of our present results* The only question relates to th upper range of normal values It will take time to settle this point, in view of the possi bilities for variation which I have mentioned* There may well he certain others with which we are not familiar. X, personally, am convinced that the final figures on the basis of present environmental conditions will be nearer 0*07 (our original figure) than It is to 0*012 (the medical students figure) Therefore, I do not consider it wise to go to great lengths to explain the differences in various groups, or the difference between individuals as studied over a long period of 'time* As. to the reduction in the use of lead sprays, let mo point out that the mean fecal lead, which in normal persons is largely an expression of ingestion has not changed appreciably since our initial observa tions* This fact also demonstrates that the sampling errors and the analytical errors in dealing with urine are concerned only with a few hundredths of a milligram of load* So much for the present* 1 am off tonight for a fishing trip and a much heeded rest* With kindest regards. Very truly yours, HAKjla RobrFXT"TehoS7*luB. RE 00154S2