Document vB4GboyQwNnyZQvQGv04Y9z9Y

July 12# l 355 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 454* During the period of years In which we have been studying this question ?s 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* 424. Our analytical procedures have been modified from time to time to give greater precision# and with the development and standardisation of our specfcrgraphic 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 hr former laboratory to the present one* This change meant better and cleaner space*.b e t t e r .storage facilities for samples# better distilled water* and better general chemical technique* XJsX We have also learned mu s h 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* , {&) The quantity of food eaten influences the quantity of lead ingestion and also the extent of absorption# upon which urinary excretlon 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* 2 (o) Physical activity increases the urinary lead output* Hen working hard, a n d 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 part in the picture which we now have* The medical students referred to in the J.A.M.A. were relatively sedentary, and all feh 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 sans general period as these medical students (l*e. within that year), gave slightly higher mean results* Thus one of our subjects showed a mean of 0.055 for a series of samples obtained during hot weather. You see therefore that physiological variation is not without significance;- ' (ii.) How for Just one other point* The discrepancy between our earlier figures, and the more recent ones is nob as great as It seems from your statement that the _ "average of 1 2 by the chemical method" is only about fionefifth of the former results". In the same article In which the figure of 0*012 for medical students la given normal mean values on other subjects are recorded as high as 0*029 + 0*002 by the chemical method. This is almost half the former mean of 0*07* X must bake exception, too, to your use of the word "average" as applied to "mean" It:.seems a small point bub actually it Is quite important for the simple reason that occasional high results make libfcle> difference In an "average" but they are much more heavily weighted in the calculation of a mean* Thus when you recognize that the difference between our former mean of 0*07 and bur present one, which would certainly* come to 0.025 i3 only O.Olj-5 it Is not very great either chemically or sta.tisfcieally. For example, the average of the means pbbained on the ten subjects studied by the continuous laboratory method (p.5 of the reprint from the J.A.M.A.) Is 0*021 * 0*002* Com paring this with the mean value for medlcal*"atudents given on p .283 of the article "On tho Normal Absorption and Excretion of Lead, II Lead Absorption and Lead Excretion in Modern Amorical Life", the difference Is 0.0i$b _+ 0*005i{.. This difference is significant statistically/"of coi^rse, but it is actually only 8 times Its own probable error. It must be at least Ij. times its own probable error to be regarded as beyond the range of purely chance biological variation. Thus, you may see that we are still dealing with figures of the order of magnitude both chemically and biologically# >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 vie 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 me 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 I am off tonight for a fishing trip and a much heeded rest* '. With kindest regards, Very truly yours, RAKgis RobrFXT"Tehoe7*llT RE 00154S2