Document 6E32nbVBDJE64wxMXj1zvQ09

Comments Concerning, AIR QUALITY CRITERIA FOR LEAD Second Draft CHAPTER I INTRODUCTION Line 2 of the Introduction contains the word "lethal'' to characterize the toxic properties of lead, presumably for man. Since the "lethal" effect is indeed rare, in relation to air-borne lead, except in the case of herbivorous animals, whose forage has been contaminated seriously by the "fall-out" of lead emitted from near by smelters, especially secondary smelters, or other industrial establishments in which lead is melted, refined or alloyed*, this is an unfortunate, if simply ill chosen, expression. It might be suspected that, for reasons other than lack of experience or knowledge, the choice was made of an expression which would convey the direst possiblt connotations of the anticipated effect of the absorption of lead ^from the ambient atmosphere. This matter of verbage, is not, of itself, important1, except, perhaps, as an indication of an attitude toward the subject, which should be dealt with in the most soberly critical manner, rather than to make use of histrionics, in view of the available and relevant information. Moreover, the next to last paragraph of the introduction provides little comfort ro those who would look to this document for a sound presentation of the facts as to the significance of the information*now available concerning the actually and potentially harmful effects of the current contamination of the ambient air with lead. The process of the "distillation of information" from the observations and publication * The serious problem of lead poisoning in infancy and childhood, when, because of th innocent or abnormal behavior of that period, large quantities of lead (usually in the form of paint) may be ingested (swallowed), with lethal effects all too often, is not related to air-borne lead. i#. *v ;; ;- "/< ?*-VS&8&<8 i-!' :.<;-1 s.^'feS'l '*v; >' i?W r:f' .; #!i". .../-----aagi; . Hu miter reoccmtqs .^.roc4ja / Kwmfcer - fP^ <? ' * ." > ?: ,;v.jv; : v1 2- V: ^ 0 1i`: S\ "X------- if : ; ... *-,.,*2^. . 4- 3; . ' *"$1 vf/ if - //. t 2o.S 'q:^f y>.d /+ 6 ";t h '/.'S 3o,^ i-3.o !il|llli yfcjt'Q-ty >07 f *>'6 xy>,o 4.^ d,/6 -,o>if " 0*/2 -r':4./i 4,/f~0,/S- . :J>,H0-fl U'-V^^vU, ! 6./T-6,f<! 4 / :? 2 1 i `r- IU %,v ,U v, i J' / I f>0 i >' 1 ,.v' y'ti:: b - -----. -. *>' i " * 'yH ;i ( ' ` ' ,. 1 '., /iw f<vX m"i. `..- i f. > ;' wr- rf? ' 'A,', sf: . . :/. ` V/'. . . - ' >v y,y y.'v 4, S ^liB 56 IfQOt O' L 46 ' ICQid *4r% loo,o ; '7 ...... . ;i jzz i -\ ' . .. &) S! f : .j.tffir ^.633 o.os'S :'; U>J*J t----0--**M;*-?A"' " ! X C' Oi^:; ' t, 0.003 f />. - 6 *<Ol T ; 3: o.'o^V ' _ ^ / knfuA*Jt, v ** ."... * 0.32 /0't4 XftZuU)a^, CoiuJt 'akt^ */ it 0. <? o 7jijO.0 3<?_____________ Y#-V;-' ` ' ; v<?v* :^> \. .' '-. \i% . *3e A*^ii' . . t ,. i Z rf :>$S' ^ >5'^ Table 12 Distribution of Y/orkmen Employed in Mixing Tetraethyl Lead with Gasoline ' I According to Milligrams of Lead per Liter of Urine if Milligrams of Lead Per Liter of Urine Jfl 9 27 19,29.............. 1931................. Composite Number Percentage Niimber Percentage Number Percentage Number Percen * 0-0.01 '2 05.6 2 .. . 5.0 19 la.3 ' 23 18. 0.02-0.03 -Jfc-- 11.1 10 25.0 lk 30. u 28 .... - 23. 0.0k-0.05 11 30.5 8 20.0 : 6 13.0 25 20. 006~0*0Y 0.08-0.09 0.10-0.11 0.12-0.13 ,-3... 25.0 Lk_ 11.1 ___ . 2 :8-3____ _ '5.6 8 6 2 2 O j.0i \ 20.0 15.A- 2 1 k.3 2.2 . -19 .... . 15. 11 _____ isi 5 k 3.1 l_=-1 0.lli-0.15 0.16-0.17 0.18-0.19 1 2.8 1 .... . 1 2.2 :2 1.6 1 -,..2^1--.... 1 2.2 2 1.6 1 0.6 ).20- 2* ...... 2* 1.6 Totals -Jii-- 100.0 ko :100.0 ..M- 100.0 122 100. Mean Probable :rror of Mean Standard' Deviation : 0.068 0 00k -- - 0.036 0.066 - 0.00k - . 0.033 - 0.003 - 0.03k # Two results 0.32 and 0 61+. excluded in calculation of means. 0.055 - 0.002 1+ .00 04 -0 1+ .00 04 so ! 01 400 Table 12 Distribution of Workmen Employed in Mixing Tetraethyl Lead with Gasoline / jAccording to Milligram* of Lead per Liter of Urine Milligram* of Lead Per Liter of Urine 192? 1929 1931 Composite Jfumber Percentage Number Percentage Humber Percentage Humber Pereen 0-0.01 2 : 45.6 2 3.0 10 111.3 .. 23- ' 18.' 0.02-0.03 _ 11.1 - -10 -25.0____ Ik 50.il" 28 : 25.< O.Ok-0.05 n ' so. . :... 8 . 20.0 6 13.0 25 ^ 20.* 0.06.0.07 -,JL- ..... ... 8 ao.o 2 k.3 -19 0.08-0.09 . ,-k,, 6 15.0 1 .... 2*2 -- 11 9*< 0.10-0.11 - -3 8.3 -5.0 5 k.1 -i-- 8.6 - -2 - 5.0 ` t .... 3.lk-0.15 ) .16-0.17 1 --..... ..JU-, 2.5 1 2.2 ... 1 -._________ _ >.18-0.19 -JL- 2.8 1 __JLtS >.20. 2* .... 4*2____ 2* - 1.6 Total* -3i_ .....lQg.t<L~ Jlfi____ 100.0 100-0 122 lOO.i aftl Probable Irror of Mean Standard Deviation 0.068 1 0.00k 0.066 - 0.00k - - 0.057 - 0*033 - 0.303 - 0.05k Two result* 0*32 and 06lt excluded in calculation of means* _ _ 0.055 _ * 0.002 -0-098 vi\ yt- -SST ~ 01 4 n ? Ui Tabla 12 ?Dltribttion of WVoorkmaaen Saploycd In Miixxing Tatraatfcqft Lttd with Oaaoltaa ^According to Milligram of Lead par LItop of Orlaa Milligram Of Lead Ftp Liter of trrlno_ I 1927 1929 193* Composite Muabcr Fcroonta/w UusabtP Percent*** iswbcr Percentage iuiBbcr Pcrccn 0-0.01 2 -5.6 2 5.0 19 'ifl. 0.02-0.05___ 11.1 10 25.0 Ik 28 ' 25*i -11 30.5 8 20.0 6 15.0 25 ..' 20J 0.06-0.07 9 25.0 . -8 2............ U.9 19 0.08-0.09 0.10-0.11 0.12-0.15 k .5 2 11.1 _ 6 15.0 8.5 2 . 5.0 5.6 2 5.0 1 _* .. 9.1 5 ^lul y O.lk-0.15 1 2.5 1 2.2 2 ''-JU* 0.16-0.1? 1 2.5 1- - 2.2 2 ).18-0.19 1 *.8 i................. - _u-- --JBL JEaMff. ; _n_________________ ___________ 100-0 ,.1,99*9..... *00- twin rabablc mi* of (can Standard 0.068 ______ O.OOffc . . 0.066 _____ ______ 0*553____ '1 * o.ooU........- * 0.009 - 0-0** -0-097 - 0-09^ Two result* 0*52 rad 064 oxoludod In calculation of aaana. 0.055 ~ 0.008 _ & 0.059 01 4 ^v'frv- '; * yP'' SPfio. -.v't.'*''*A* ^Hi'l.:'',.' '" -, f;. . !Br i' ' i ` + >. .*, X ' ', >;.- ,k ' fitu .. pkKyk.N; j^,'. ;^ I 'M'"' ' ' *5 - i . .''.' 1:; v `t '-! v -. - . ^ . / xtt, <77% j --y . uu*U 7 M- 'iim, ffkh ;<!;>1'ifi f . ; i ** - ->: v V- - ' ? cN* , 'i < l* > Aj& -j't!-/i' >:l'rb: "- .-.* . Vd , vAV'- V *T\ V* " 4^0--. \ tea 01 406'.' Cc j -h aj c ) ^ t /i^Xf i kJ ktJl feud- (7#)(4^ 7 uf1 v ' .. 7 , - m ' -~ . --v*,- "* '' * v#i 1 rO) * I Tim e in Wee ifs Wf t e i^ Ce s s a t i o n o f cxfposuif flCf/jMGTO/HLYOut put o f Lead i h Ui^ip e Foi?Suc c essive Wf e/csFe w ^ T/m f //v W ff/fs FrrE f Ce s s a t i o n o r-- -- - W A> f/(Posuife Tim e in Wee/(s flFTEfg Ce s s a t i o n o f L\Posurge 3 )]/}S M )cJJ0 M 0 llK S JjT iU jysT l3 JfA i s /u s s is o n r lia j s j o w j n i r w s jjo H id in g A jw f fl/E rfftG E O fl/Ly C o rtC E N rrtflT io N o r L e a d i n U r i n e For? S u c c e s s / \/e We e ^ s A f t e r m 9 0 c /J (J J O A /O /J .d S 'S 'J J d / J U ^ 9 j/J J /y A// 3UJJ_ Because of the lead intoxication, the previously neglected luetic ndition was permitted to go untreated until such a time as it could be inaugurated without risk. The first treatment (Salvarsan) was given on the seventy-first day in the laboratory. (Cf. Figure ____ and legend.) No other treatment of any kind was employed during the early months of the study, since the subject was in no distress, and since we wished to observe the lead excretion uninfluenced by any factors of our own making. The diet of the subject was varied and adequate, and entirely of his own choosing. Since food was provided out of experimental funds, the factor of cost did not influence its quality or quantity. The amount of lead in the first sample of faeces (l.72 mg,) falls far short of what it must have been on the day fcllcwing the cessation of exposure. The mean figure for the samples of white lead workers similarly exposed was 7.6 milligrams. Attention is called to this fact as a reminder that this subject, seen two weeks after his last workday, could not provide a faecal sample which bore any evidence of the exposure of that day. However, the faecal lead is high, and is subject to v/ide fluctuations. Beginning on November 18th, and occurring from time to time until the middle of December, s a new phenomenon appeared in the faecal excretion, which, required some explanatfOTS""' High results, entirely outside th previous range, and in fact, outside any reasonable excretory range, began to appear. A survey of the diet list revealed a perfect correlation of a meal of fried or stewed rabbit with these occurrences. In order to avoid similar results the subject was warned against the inclusion of game animals of any type in his diet. Such aberrant figures promptly ceased to appear, snd were not seen again except on two occasions, one in February (4.40 mg.) and one in March (3.00 mg.). These may have resulted from an unusual amount of lead arsenate on fruit ingested on these occasions, but no certain explanation can be given The other high points in the faecal excretion are the result of the accumulation of faeces in the alimentary Jrract during the periods of constipation, which were of frequent occurrence. The trend of th< alimentary lead excretion is gradual and unmistakably downward. If the average amounts per week are plotted to form a curve, there is a downward trend over the entire period of thirty-five weeks, with numerous irregularities corresponding to those which are seen in the daily graph. At the end of this time, the faecal excretion corresponds approximately to the level of the faecal excretion of . / tv a. <L*--> ' nOTTua.'- -paraaas. Clearly, it cannot have gone appreciably lower. The irregularity of the curve defeats any fine attempts at its in terpretation, Nevertheless it is important to note that there is no evidence of a critical break in the level of faecal lead excretion either at the time of disappearance of symptoms (cf. the arrow at December 10th), or at any other time. Undoubtedly, the lead cbntent of the subject's food was a factor in the irregularity o!^ the ^faecal / curve. Despite this disadvantageous factor, it seems to be a reason able assumption, from the facts, that as the quantity of lead in the tissues diminished, the excretion of lead in the faeces diminished also. When tii'W"**!inary excretion is considered, the results are yet more striking. The high level at the start is maintained with only a fleeting dip for two weeks, after which it slowly slopes off, to be elevated again to a remarkable degree by a mere increase in water intake and elimination. After this period it falls to a level which is essentially normal, being slightly raised during a period in which lemonade was administered. rhe increase m this instance is not definitely higher than would be accounted for on the basis of increased water intake. Again there is no critical point in the curve, but only a gradual irregular diminution. The period of work at the end of the observations was not sufficiently energetic to demonstrate any certain effect. Nor was it carried out with such uniformity as to establish the negative fact. In fact, it introduce an undesirable factor into the observations, from the point of view of the subject, and to such an extent that relations which had been mutually cordial and beneficial became somewhat strained. When this situation developed the study was abruptly terminated, since it could be continued with profit only through the perfect cooper ation of the subject. 3y this time, the subject was in excellent health except for the irreversible sequelae of a luetic aortitis, so far as examination indicated his physical state. The concentration of lead in the blood showed a general correspondence in its hehavior to that of the urinary excretion. It is particularly noteworthy that during the period of high water s intake the amounts of l*ead the blood were too small to be de tected by the methods emplpyed. This is precisely what would be expected if the greater lead output in the urine was produced by the simple leaching out of soluble lead, rather than by an inter ference with the mechanisms of lead distribution in the tissues. The occurrence of basophilic stippling of the erythrocytes during the study is in strict relationship to the other observa tions except that it disappears at a much earlier date than do the other abnormal findings. It reaches an approximately normal level at the time subjective symptoms vanish. From this fact one might attribute an unwarranted importance to the phetoomenon, but in con sideration of the frequency of occurrence of high findings in persons who have no symptoms or signs of intoxication, the signifi cance of the drop in this instance must be left to speculation. Legend for Figure ____ (Smith) The daily excretion of lead in the faeces is plotted on the lower curve, the cross-hatched portion indicating the amounts found by anal ysis, the solid black representing lead in milligrams per gram of ash. l*f it --* `-M. The daily urinary lead excretion in the amounts a* found is in solid black in the upper curve. The stippled areas refer to the volume of urine voided. The topmost solid black areas are set down on the dates on which 50 c.c. blood samples were obtained. The projection of these blocks below the top line, expresses lead in the blood, in milligrams per 100 c.c., on the same scale as the urinary lead is plotted. The number of stippled erythrocytes found in fifty fields of the daily smears are shown by the dots on the broken line curve. The zero point of this curve is represented by the continuous straight line which extends across the lower (faecal) curve. j At certain points where amounts go beyond the upper limits of /the curve the amount of the item in question is inserted in numbers. Any losi samples are so recorded. The absence of records on other days are due to failure of alimentary evacuation. Days marked I' at the top or~ the faecal curve are those on which the subject' ingested fried or stewed rabbit. The days similarly marked are those on v/hich a treatment with salvarsen was administered, in the treatment of previously neg lected syphilis. The value of the facts displayed in the study of the foregoing subject in the diagnosis and treatment of lead poisoning may be left for later consideration, For the present, let us deal only with their significance in the clarification of the factors which influence the magnitude of lead excretion. It has been shown that lead excre tion varies with the extent of daily lead exposure. It may now be recognized that it also depends upon the amount of lead which has been absorbed into the tissues. An objection to this conclusion may be raised to the effect that the subject was not necessarily typical or normal, in that he had a disease (syphilis) which may have influenced the results. That this was not the case is di own by similar observa tions on another subject, a young, apparently healthy negro, whose exposure had been brief but severe. This subject, years of age, had been employed in a white lead plant for Impending unemployment brought him into our hands when we were in search of a suitable subject. He came to the laboratory directly after a day's work and after a phys ical examination he was accepted as satisfactory for our purposes. The significant items of his physical examination include Figure ____ shows the results of four months of daily observa tions, A number of samples of faeces, and two samples of urine were lost in the first and second weeks, for a variety of reasons, but there were no difficulties thereafter. The subject proved to be a reliable and cooperative participant in the experiment. 01 415 In certain notable respects Figure ____ differs frcm Figure ____ The faecal curve in Figure ____ begins with a high point, followed by an immediate large drop, after which the initial level is never regained. This is a characteristic effect of the abrupt cessation of exposure to lead dusts, the result of the swallowing of lead deposited in the upper respiratory passages on the previous day being apparent in the faeces. From this point on .the amounts of lead appearing in the faeces of this subject are smaller than those in the corresponding period of the observations made on the other subject. This, in itself is significant, for the exposure of the two men was of the same type and presumably of approximately the same intensity. In the first case, however, it was prolonged, while in this subject it was of short duration. Presumably a smaller amount of lead accumulated in the tissues during the shorter exposure, and there is a corresponding diminution in the rate of excretion. There i3 a further difference in that there is a more gradual slope to the /' curve of diminishing laecal lead excretion. Unfortunately the obser vations were not continued until the normal level was reached, and it is impossible, therefore, to compare the two subjects in this regard. (It is of consideraoie practical importance to note that the evidence of significant exposure persisted for four months.) Despite the differences in the faecal excretion as represented in the two figures the general facts are in correspondence. There is a gradual decrease in the magnitude of the daily excretion, and there is no critical change at any point. In fact, the various experimental efforts to influence the rate of excretion as recorded on the curve, have had little or no clearly demonstrable effect, with the exception of magne ium sulphate, which was certainly responsible ior the elimination of an increased amount of lead, with the increased activity of the alimentary tract, on the first day of the treatment. This was admm- Check this in or- iginal data. istered of five in four doses daily, at four hour intervals, each dose consistin grams of MgS04.8H20 dissolved in a minimal quantity of water, The urinary graph shows much the same general trend as does that of the faeces. Two peaks of unusual magnitude occur on the eighth and thirteenth days respectively, coincident with the ingestion of ab normal amounts of water. The other irregularly spaced high points or low points have no necessary relation to the materials administered at various times as indicated, since similar high and low points occur elsewhere without relation to treatment. It is especially interesting Check to note that the administration of calcium lactate in four doses of two amt s in or- grams each at four hour intervals over a period of four days failed to iginal data, cause an appreciable drop in the excretory rate. The biliary drainages on the seventy-first and eighty-fourth days respectively served only to demonstrate the presence of measureable amounts of lead in the bile. The lead in the bloo3 of this subject was less in amount, than that four/d in ^the blood of the first subject for a corresponding period. However, just as the lead excretion failed to reach a normal level, so ( the blood failed to reach a point where consistently negative results t, were obtained. The observations as 'to the occurrence of stippling of ery throcytes were uia'iJNs"woraevhat irregularly. They require no comment. AH 01 4 i / 'i $ v < : a. rc * / 5~6 <*'>'>& -S ,Tll! Hvoaa w v h v h o l--lo ns^sxit U10S Uj J' 01 418 ETHYL GASOLINE AND ALL GASOLINE SALES IN U.S. 1926 - 1951 Year 1926 1927 1928 1929 1930 1951 Ethyl Gasoline Sales in U.S. 79,315,600** i 288,484,450 - 527,803,050 1,241,416,050 ^ 1,854,505,900 1,970,389,463 All Gasoline Consumed in U.S.* 2( >9,075,858,000 9,437,188,000 /) { 10,698,787,000 / 13,549,879,000 ( 15,759,039,000 16,415,705,000 * Figures for All Gasoline Consumption reported by A.P.I. do not include- 111. for 1927,1228,1929. Mass.,N.Y. for 1928. .. N.Y. (Jan.through April) 1929. '' N.J. (Jan.through June) 1927. ** This figure includes only Ethyl Gasoline sold from Sept, through Dec. 1926. The record of 1926 Ethyl Gasoline Sales is incomplete. (3? ^ c- y * c 01419 Chapter VI An Appraisal of the Lead Hazards Associated, with the Distribution and Use of Gasoline Containing Tetraethyl Lead* 1. The Nature of the lead Hazards The development of a motor fuel containing tetraethyl lead rais certain questions in industrial and public health which have claimed an unusual amount of attention* In an early stage of the new commerci enterprise it became apparent that the manufacture of tetraethyl lead and the blending of the concentrated fluid employed in the preparation of the commodity known as Ethyl Gasoline* was an hazardous occupation which furnished unique opportunities for the rapid development of lead intoxication. The serious dangers of these manufacturing processes have no relation to the problem with which we are concerned in the present discussion. However, the initial confusion of the actual hazards of manufacture with the problematical dangers arising from the use of the finished fuel, has apparently persisted in many minds. Therefore the distinction between them must be made clear. ) Pare "tetraethyl lead is a heavy, colorless, oily liquid which is peculiarly difficult to retain within jointed receptacles and pipe lines. It is insoluble in hot or"cold water, but readily soluble in alcohol and acetone and miscible in all proportions with fats and oils. As might be .suspected from the latter property it penetrates the un broken skin of animals. Indeed skin absorption alone may result in the rapid production of acute illness and death in experimental animals From a purely physical point of view, the volatility of tetraethyl lead is low, but considered in toxicological terms it is dangerously high, since 'at ordinary temperatures air saturated with it* vapor con tains approximately five milligrams of lead (as Pb) per liter. This concentration is lethal for experimental animals (rabbits) in a few hours,^ a fact which demonstrates the ease with which tetraethyl lead 01 420 pen-orates the pulmonary epithelium. Under certain ccr.aitions, notably in the presence of sunlight, tetraethyl lead is unstable, breaking down J yield water-soluble, crystalline triethyl lead compounds. Slight agita+h serves to suspend these fine crystals in the air, when in a dry state, thereby producing a dust hazard which has the aualitv - unique among lead hazards - of providing sharp warning of its presence, in that a very low concentration of these substances induces irritation of the mucous membra with weeping and sneezing. The dangers associated with the preparation and handling of i te traethyl lead are fairly obvious, when these properties are recognized. Unicrtunately, this information was not available when the manufacture of the product was first contemplated. It is not strange therefore that when the production of tetraethyl lead emerged from a laboratory scale into an incipient commercial stage requiring factory facilities, cases of -<Sp. , lead poisoning of the most serious type occurred, o3s^-ciated. vri-th the sudden onset of cerebral symptoms and with a high mortality. Without entering into an irrelevant description of the (Various Steps by which Ethyl Gasoline is prepared for the market, suffice it/to say that the hazards of the manufacturing processes are inseparably asso ciated with the characteristics of tetraethyl lead described above. The hygienic problem at every point consists in the prevention of skin contac with tetraethyl leaden the part of workmen, and in the maintenance of conditions under which the vapor of tetraethyl lead is not present in the air breathed by workmen. Because of the sharp localization of the dangers, they are amenable to exact and adequate control; nevertheless the potential hazards are great, so that safety is maintained only by continual vigilance in the prevention of accidents a.nd in the avoidance of careless practices. The hazards associated with the handling and use of the finishec product, Ethyl Gasoline, differ both in quality and quantity from those 01 421 v-'hich lurk in its preparation. Nothing could demonstrate the difference in the magnitude of the potential lead exposure of the two sets of condi tions- in a more pragmatic manner, than the failure on the part of Ethyl Gasoline to produce a OEBfftet substantiated case of lead intoxication in the the nine and a half years of its continuous use, up to the present (July, 1932), in certain parts of the United States, This basis of dif ferentiation is the more significant when one considers that the hypo-thet- V. ical opportunities for the absorption of lead, as a result of the distri bution of Ethyl Gasoline, are so. varied and so widespread as to defy regu lation. But there are other points of difference which have not required the test of experience for their recognition. Ethyl Gaaoline contains tetraethyl lead in amounts so small that the solution has lost the essen tial toxicological properties of tetraethyl lead. Thus, whereas tetraethy lead alone, or in high concentration in gasoline, is absorbed through the skin rapidly, its absorption is retarded greatly by dilution in gasoline. Indeed we have been unable ^to obtain evidence of appreciable lead absorp tion through the skin of experimental animals - after their prolonged expos ure to concentrations of one part of tetraethyl lead per thousand parts of gasoline, by volume. ' The importance of this fact is two*'fold. Not only does it indicate the improbability of the ,absorption of lead "out of & Ecotnote s Among the thousands of persons .in the United States engaged in the handling of Ethyl Gasoline or otherwise exposed to it3 possible dangers, f-sw e r- thaw-'1- on a -kundr od cases of real or supposed injury, have come to the knowledge of the author. Host of these have had no relation- ship.to lead absorption. Only three have hdw<*. Sgggsiijgf oi-sm- re-sembl&nce to-caaaa--&-1 sab---eatitan,~tjtr"bo pegarAsd as abJUu Gartful -ot-neb/ of tfteru cases fa-il'edrlTi each instance to ost>abli-3a- a>-aatisfnctnrv basis for t^0 Gasoline on the part of persons vho come in contact with Ethyl Gasoline, bn c. it also establishes the certainty that any minute amount of lead which might be absorbed would be unable to distribute itself in the fattT tissues ana the nervous system in the manner characteristic of tetraethyl lead v/hen absorbed at 9. rapid rate# An equally important effect of the i dilution of tetraethyl lead with gasoline is the elimination of the dange vr of inhalation of lead* to a very large extent. The difference between the volatility of tetraethyl lead and the various gasoline bases with ii y, which it is mixed, is so great that approximately half the gasoline may be evaporated before dotoo-tablo amounts--eS lead.axs found in the vapor. >-- ^ A l *-'*4 *; It follows, ft?om this that the vapors rising from tanks containing Ethyl Gasoline do not contain dote-jwakc amounts of lead. However, this does not mean that no tetraethyl lead is evaporated under any of the prac tical conditions of handling and use or spillage of Ethyl Gasoline. * Although years of experience have not shown the existence of dan ger to the community in the use of Ethyl Gasoline, and although the qual ities of the fuel, as described above, explain this result in a large { measure, the potential hazards associated with the general dissemination of a product containing lead may not be dismissed lightly. A full oppre0 x cl m of the nature of these hazards is required for an understanding of the problem whflJH'^bhey provide for investigation. Ethyl Gasoline is handled at refineries, bulk storage plants, filling stations, and in public and private garages. It is transported from one to another of these sites in tank ships, tank cars, tank trucks, barrels,and tins. In the United States and in Canada an overwhelming pro portion of this motor fuel is dispensed through filling stati on pumps. In England and on the European Continent, a large amount of gasoline is distributed in two-gallon cans which are filled by essentially automatic machines at refineries and at storage points. Large numbers of persons (Le i 01423 come in contact with Ethyl Gasoline to a greater or lesser degree through spillage, as an unavoidable result of the various meti'ods of distribution. They also inhale vapors from tanks, hose lines and from surfaces on which the gasoline is spilled. At refinery loading racks, at filling stations and at other points where gasoline is handled regularly, the repeated spillage of Ethyl Gasoline may bring about the accumulation of higher boiling petroleum fractl ons, and of small amounts of tetraethyl lead, by reason of their absorption into wooden platforms, or other surface mater^- ials such as concrete, asphalt, gravel, cinders or earth. Under these con ditions some porton of the tetraethyl lead is evaporated slcwl.y, and the remainder undergoes decomposition. In either case, opportunity for inhala tion cf lead on the part of persons in the vicinity may be provided. though, no doubt, most of the accumulations are dissipated by frequent f'AiUj hosing, or by rainfall./ -- d-jJ ,w The sale of the gas line to the consumer takes it into the provinc- of the general public where some degree of exposure to skin contact and to r> vapors may occur. Of much more importance, however, is the appearance of / a new Bet of conditions based upon the combustion of the fuel. Tetraethyl lead is converted, thereby, into finely divided inorganic lead compounds (chiefly lead bromide), which are deposited, in part, along phe exhaust :\ system, but which, otherwise, are discharged into the atmosphere with the- exhaust gases of the motor. The extent of the accumulation cf exhaust gases from many automobiles in busy city streets, and especially in poorly ventilated areas where cars operat* in considerable numbers, becomes a question of considerable importance. Thi3 aspect of the matter concerns the entire urban populat on, but it develops a special significance in the case of gasage mechanics. Garages, in general, are poorly ventilated. Few of them, indeed, are equipped to maintain an adequate dilution of exhaust gases, under the most favorable conditions, and, when doors and windows are closed, in cold weather, ventilaU on is often negligible. For this reason* through the winter months, many mechanics develop late afternoon headaches from the absorption cf carbon monoxi. de. Their exposure to lead in the exhaust gas cf automobiles burning Ethyl Gasoline is greater] therefore, than that of any other group of persons in the community. Further, the handling and the spillage of gasoline, the adjustment of car buretors, and the repair of other parts of the car cften involve skin con tact with Ethyl Gasoline and with lubricating oil which mgr contain minute amounts of tetraethyl lead. The spillage and evaporation of gasoline may leave behind the less volatile tetraethyl lead to be slowly volatilized at a later time*or to decompose, and by so doing to add to the lead dust in the garage. In the dismantling of motors the combustion products cf tetraethyl lead may be encountered by the mechanic, and although these cannot be absorbed through the skin, they may be a further means of con taminating his hands, his clothing and his surroundings.' The-cumulat'rdn od--lead dust within the garage., .as , a result-o.f--the^-er;factoris ," together _ V-- ithr'the' settTThg--o- > eamended by that, whicih^^eitranaLos f-rom~ therepair" of `electrical storage hatt-erieSf,--the- use of paint g- arrdu g cTd'er and fr m such similar practices whdnh_-A3te--ettri*ired- out1 c ommor.i7r"in--thrg'-'Tvpafr--of- nrjrttrrrtobii'es^ tT o th.eJ,ii i p e must regara'h i ii il uln i.-.i irrkrd rni.ihy ~ ^ . . t' - -A f V- I'-* **kr~S. LA,.** > Cne further point must be iji n~b`i' ij----- mrmitg nnri mired -mt~ -air Zst,- / -J.1 -.A'.hS. _,c -.d-ftu* -*v --t-/ t- f- - 1 - J ^' *. ``-3 .1 f . ,, * .* considered in a complete analysis of the potential public health hazards cf the use cf gasoline containing lead. The derosition cf lead compounds upon the highways, city streets, - in short, upon the surface of the earth - may conceivably influence the amount of lead breathed by animals and men, as well as the quantity incor- / ^orated in and deposited upon vegetation employed as food. 01 425 .r.e uai i 'a iv - character of the lead hazards derived from the use of Ethyl Gasoline is based upon the methods of its distribution and use. The general magnitude of these hazards is dependent upon the xtenof the distribution of Ethyl Gasoline, the volume of consumption in a given area, and the period of time over which distribution and use have, extended, these factors being modified to some extent by the variations in the lead concentration in gasoline, which have occurred in various sections of the country. Accordingly a complete representation of the situation requires some attention to these details. Ethyl Gasoline was distributed first in the early months of 1923 in Dayton, Ohio. A few months later it was on sale in Cincinnati and in the district around Dayton and Cincinnati. Thence its use wa3 extended to middle-western and southern United States, into areas represented most satisfactorily by the cities of Chicago, Detroit, St. Louis, Jacksonville, Atlanta and Savannah. The quantity of Ethyl Gasoline sold up to 1926 cannot be estimated accurately, but it was limited to this general area, and there was a steady increase in the volume of distribu tion during this time except for a period of almost a year beginning in May, 1925. At this time Ethyl Gasoline was withdrawn from the market, pending an investigation of the United States Public Health Setvice, though for various reasons its use was not interrupted in certain areas in which it first appeared on the market, - viz., in the cities of Dayton Cincinnati, Savannah, Jacksonville and Atlanta and their vicinities. The resumption of distribution in 1926 resulted in the rapid expansion of the area over which the fuel was used. This expansion continued until Ethyl Gasoline had become available in all parts of the United States. Table _J__ demonstrates the spread in the distribution in terms of the datesat which sale began in various cities of the United States. The duration of continuous distribution for these areas is also recorded up to the time of the observations which are to be described. The approximate quantities of Ethyl Gasoline sold during the years for which tea 01426 TABLE Period of Distribution of ~"thyi Gisoljne ir. irlous American Cities Up to October 1'3%S\ Locality ' .lyton, Oh 1' incin-'ati, O^lo ..- heeling, W.Va. Chicago, 111. Detroit, Mich. t. Lcnir, -o. lunsas City, Do. inneapolls,Minn. Date of First D5 tribution February 1923 April 1923 |} Summer 1923 | Autumn ; Autumn j Spring 1923 1923 1924 j Spring j Spring 1924 1924 Interval Discontinv gk'Ace none none . .A /f 25* -t -1 t? same. same HP 1 '.M Years of Continuous Distribution 6.7 6.5 3.2 3.2 3 3.2 3*2 il'-vaukee, A'is. Spring ' a11imore, '.Id . amingfcon, D.C. j Spring j Spring Tin Antonio, Texas Spring amah, Ga. .tiunt-a, Ga. /acksonville, Pin. Autumn Autumn j Autumn ov/ Orleans, La, love land, Oho j Summer Summer hilndolph!a, In. oston, Pass. Summer SUUBIBU Denver, Colo. Summer Ian Francisco, Cal. Summer Los Angeles, Cal. Summer Spokane, Wash. Tulsa, Okla. Mew Yorn City Summer Summer autumn 1924 1924 1924 1924 1924 1924 1924 1926 1926 1926 1926 1926 1927 1927 1927 1927 1923 ;-b tvaae 4\ snme ; -stwae :psame- none none none ( none none none none none none none none none / none y 7 3.2 3.2 3.2 3.2 5.0 5.0 5.0 ` 3.2 3.2 0*2 3.2 O-- * > nA- * W ) u j) % Unt n4-f o 2.2 1.0 i te 01 427 figures are available are shown in Table It should be noted that the general areas into which Ethyl Ga line was first introduced have maintained the largest proportional and gross consumption. The concentration of tetraethyl lead in gasoline up to 1926 was maintained at three cubic centimeters per gallon - approximately one part of tetraethyl lead in thirteen hundred parts of gasoline, by volume. Since Hi at time, the lead concentration has varied in accordance with the quantity required to bring the available gaaaline base up to a definite standard of performance in a test engine, except that the amount intro duced has not exceeded three cubic centimeters of tetraethyl lead per gallon of gasoline. The average lead concentration by years for different regions of the country may be seen in Table __. A brief study of the contents of these tables is sufficient to give a clear indication of the areas in which the greatest opportunities for lead exposure have been provided. They also yield a graphic concep tion of the,,proport ions of"the problem vhich confronts us. It /is not to be supposed that the possibilities of danger in the general use of Ethyl Gasoline one unnoticed up to the present time. On the contrary, numerous experimental inquiries have been carried out. Thus the United States Bureau of Mines ' began an investigation of the hazards assoc iate<u*ia&. the exhaust gas of autofaobiles employing Ethyl Gasoline as a fuel, in the autumn of 1923, before the new fuel had devel oped more than a localized distribution. The further investigations of the Bureau of Mines'^extended,SJywHfj other phases of the question. The / United States Public Health Service studied the matter in 1925, and the Ministry of Health of Great Britain ^critically reviewed the previous experimental work and made further contrubutions to it in 1928. Each of the latter two governmental agencies acted under the guidance of its own committee of experts appointed especially for that purpose. Our own 01 428 *-3 >Mo*-3 CO cCce^aD*t CD ct o O pca PcCWcDtt Vo*O3Jr 3! ct O3OMP3X*" -cM9XPo P ccPJtti 3cOOt PCD PM3 ct a0g3(PS<~=Pp33Wy>*Mpc3a0s 9CD -p 33 P H? t-**5 31--JiCS a<D SP3P' amP *CtpO-1*Ln3pHOcj* 3t3cO*tr "3n -T O3 o OPOPct CO 5cMP3Hct*t cpcptt a 01 CO o CO o CcnO CD o ai CD o O cn OJ o M -4 OO O cn CD o o o 00 a M o CD o CO o OOJJ O a Mcn 4 -c4o o> OoJ M O MMO Cn o o o o o cn M 0 0 o OMJ OJ oo CO CO Ol o OJ Cn M M cn OJ o CO M to CO o M OJ Orf*I o CO o Ma> o C D o -M3 *CO o 0 0 o OtoJ o tOoJ CMD oo M -41 o C O OJ Mo M a> OJ CD co to -3 00 rf* CO<D3J ft c CO o MOJ CO cn o cOnJ Mcn to o CO oa c o o o o oo o CO cn cn cn cn M cn cn Mto cn M-4 O J OJ M o 03 itei 01429 CB 5 *C4O h<-l p 5a45 cCt/J343 ct oK{ a Wa 2. <*j *2 M 3 p 3M P CL 3 a a >e> 3'-* 3CD MCO f0t 0D f3t CL H w ^o ca* ct cr D ct v* caCO>+ cr 3o cn QD oO mh^wCtDa 3M> 3 3* MHHM MO 3 o Q CO 3 P CO CO 01 o M Mo CO o o to cn Q9 tt 0 OO 3 0*10 CO 3 MO M O OHttS cr m 3* 3 MP O3 M<*4 c+ 0O0 CO 01 > Tn3 3o X a cat 9ppo p3a oo xas p P3 OJ o cton o * OJ rfk CO -4 CO cn M ca to 4* to CO 0c0n 03 -0 oo MH* ctr?f 03M! 3a v3j* M O a3 0) ca 01 O *1 Ot-t- o aco O cPo O MO M O I-- H c-t" (-> MO rctt 3* *O3 O3o3 CO CO 3 CD 3 MO M Pct CoO M WQ3 3 c3*t cd a 3O p3 CO 01 o M CO 0 0*0 co i DD M3 O Cmt3-D"* Vwc3{t*M occ3at P CaO> m t>ro 30*<3cj"t PMH oMOO3a H3O* CO pco 01 co O 'M OM CO CO <9 31 a 3O O3 3 mi t0*3 0C3O Hc*t o ct 3 O -=3-t M *M4(CWt i3 3D M MO cCcooO aPo MM 3 9 M3 < P3 P3O 5 PCO O M 3* CD 3C MO l!L 1* 0rfl0*fl 03 P O P M CD ca 3 MO M O O M cf O ao3 ct 9 at* y3 3ct M CD M P ct CO cn 9 ct CD CL Cc ct P ct p TABLE VA Average Tetra-ethyl Lead Content of Ethyl Gasoline In Various Areas Of The United states from 1926 to 1929. Distribution Areas of United States- Dew England ^tntes and New York Pennsylvania .tlantlc Coast States Average Tetraethyl Lead Content in Cubic Centimeters per Q 1906 1927 *1 niJ no 1929 * 1w 1.7 1.1 1....0............... 1,6 1.2 1.2 l.'i 0.9 1.65 1.5 Ohio 0.9 Kentucky, Georgia Florida, Mississippi. , 1.0 md Alabama Louiaianna, Arkansas 1.2 i i 1.7 0.6 1.1 \ i 1.7 1 1---------- t 0.9 * 1.5 1.9 1.3 Central States "exa s, ^ ilaho-va :ocky ^ount&n States Tiest coast States ^L #A5 l.~ 1.3T'"" mm 1.3 1 1 I 1.7 T i i .0 i 0.7 / ;2,s i ; j2. G : i '2.4 . *> m \j 2.0 2.7 . I 1 ; 2.4 .1 X1 *w5 01 430 observations, beginning in 1924, have'dealt with several aspects of the problem. First in 1925, and successively in 1926 and 1927, we investi gated the lead exposure of persons engaged in the handling of Ethyl Gaso line and in the repair of automobiles using Ethyl Gasoline as a fuel. These have been described in detailed reports / to the United States Public Health Service, and to the Ethyl Gasoline Corporation, whose officials sponsored the work. The fourth of such field' invewtigations is the subject of the paragraphs which are to follow, I shall not discuss the methods or the results of the earlier experimental work carried out by ourselves or others, except to point out that none of them disclosed evidence of danger either to the health of persons engaged in the handling of Ethyl Gasoline or to that of the general public. In the light of the which they have furnished, there can be little doubt that some of the hypothetical hazards which have been described, do not exist. However, I shall disregard such considerations for present purposes an<f shall confine myself to the presentation of observations which were made iri the autumn and winter of 1929-30, employing certain items of our earlie data only for purposes of comparison. ,~^hese observations had--the -purpo-se / ,an answer to one question. - Is the magnitude of lead expos ure arising from the combined hazards of the use of Bthvl Gasoline such a.-. to iring about appreciable lead absorption on the part of any group of individuals in th unityjr?j. m terms oi ,he facts presented ir. pr*8?!; pages of this 'volume, this Question should be answered adequately through the study of groups of persons who have had the severest and longest exposure to such lead hazards. Accordingly, groups of subjects have been selected for detailed study of the effects of their occupation upon their health, and upon such physiological processes as are specifically influ enced by a significant increase in lead absorption* 01431 2 . The Selection of Experimental Subjects. Table ^ sho^s the numbers and types of subjects selected, together with th* locality in which they were employed* The three croups of workmen who experience allvmeans of exposure to the possible hazards associati with the use of Ethyl Gasoline are adequately represented by fifty-six filling station attendants, fifty tank-truck handlers of such gasoline, and two hundred and one garage mechanics* The filling station attendants were chosen with attention to several matters: men who had been employed as subjects previously, who hid been handling Ethyl Gasoline for the longest period of time, who had handled gasoline containing the highest concentrations of tetraethyl lead, and who handled the largest amounts of Ethyl Gasoline daily, were especially desirable. Until May of 1935 a small metering device containing a liter can of Ethyl Fluid was used on filling station hose lines to treat gaso line with the lead mixture as required* This method of distribution brought about some degree of exposure to concentrated tetraethyl lead on the part of filling station employees* Therefore, those subjects^whose employment dates back to ih is period have had opportunities for 7the ab sorption of lead from this source* They were particularly favorable sub jects for the determination of the maximal lead haxards associated with their occupation* It has been pointed out previously that in the cities of Dayton, CincSavannah, Jacksonville and Atlanta there had been no interruption in the distribution of Ethyl Gasoline a. nee its introduc tion on the market* Furthermore the employment turnover of filling static attendants had been so slight that i.t wss not difficult to find a satis factory group of men who had dispensed Ethyl Gasoline since it was first marketed from their stations* The consumption of Ethyl Gasoline had been greatest in certain central states represented by the cities of Dayton, Cincinnati, Detroit, Chicago and St. Louis* In these cities individual attendants at certain TABLE DISTRIBUTION OF SUBJECTS ACCORDING TO OCCUPATION A T> LOCALITY Locality Number of Number of Filling Sta Tank Wagon tion Atten Handlers dants Exposed Exposed to to Ethyl Gas. Ethyl Gas. r/1 - i' 56 #101--'150 Number of Garage Mechanics Exposed to Ethyl Gas. 301---'50l Number of Number of Barrel Fillers Barrel Fillers Not Exposed to Exposed to Ethyl Gasoline Ethyl Gasoline r201 -f227 * 251 - ,7272 Cleveland Ohio Cincinnati Ohio 11 Dayton Ohio 11 Chicago Illinois 6 Detroit Michigan 1 St. Louis Missouri 11 Kansas City Missouri c; >, Minneapolis ''in' esota Jr; cksonvill 3 Florida 6 Atlanta Georgia 10 Milwaukee Wisconsin Boston Mass. Wheeling W. Va. New York New York Total 56 1 10 9 11 , r> 8, 1 ---- 6 4 50 ggrl 01433 15 13 15 13 12 48 ( 5 5 5: 5 5 50 10 201 27 27 22 22 well located filling stations had handled more Eth.. 1 Gasoline than had similarly employed iipteui in any other part of the country. The tank wagon handlers were selected on the basis of the severity and length of their exposure to Ethyl Gasoline. Twenty-seven of then had served as subjects for study in 1927. Thus a direct comparison of the results obtained on the two occasions was made possible. The garage mechanic group -is* made up of one hundred and nine per sons who Nhav\ been working on cars which used only Ethyl Gasoline, and an additional ninety-three who have been repaining cars of ^ich a high percentage used such gasoline. Effort was made to find all the mechanics in the United States who had experienced prolonged exposure in garages in which all the cars had used Ethyl Gasoline exclusively over a period of several years. Ten members of the group had been employed in a public service garage in Dayto n Ohio, in which Ethyl Gasoline had been the exclusive fuel from 1923 to the time of the present investigation. Thirtys-nine subjects had had from three to six years of daily repair work cn cars in vrhich Ethyl Gasoline was the exclusive fuel. The entire group was composed of subjects who had been emplcj'ed in continual repair / work cn fleets of cars. From every point of view the subjects selected for examination had the maximal opportunity for exposure to lead arising from their respective cccupajuafifijt rel ationships to Ethyl Gasoline. The garage me char ic 'group is entitled to special c d ns'ideration since it is composed of men whose occupati. on combines all the potential lead exposures derived from Ethyl Gasoline in an intensified form, together with certain other lead exposures which are not related to Ethyl Gasoline. It is for this reason that it vras expanded to a large number at the expense of the less exposed groups. The barrel-fillers referred to in Table vrere included among the subjects chosen for the present investigation for a specific reason which will appear later. The data are available through a fortunate tm 01434 combination of circumstances. Several years of observation of persons vr.ose occupation involved considerable exposure to gasoline ^aroused our interest in the influence of repeated and prolonged gasoline absorption. Accordingly search was made for a group of subjects whose exposure to gasoline was severe and uncomplicated by other factors. In the summer of 1923 such a group was found in a refinery in which large quantities / yd B 01 435 of gasoline were put into fifty-gallon barrels for transportation. The barrels were filled in a specially constructed room provided with forced ventilation. Despite the magnitude of ventilation the concentration of gasoline vapor was hi,,h enough to be immediately disturbing to one who was not accustomed to such vapors. In addition, the skin, clothing and shoes of. workmen were frequently and almost continuously soaked with gasoline. The barrels were lined up In a double row along corresponding rows of pipe lines each of which was. provided with an elbow, a flexible hose and a float valve. Each hose line with its valve w s inserted in.'a A drum, and the valve was opened. Gasoline flawed in at considerable pressure until the level of liquid in the drum released the valve, thus closing It, Occasionally the valve refused to work properly, at which time a stream of gasoline rose from the drum and thoroughly drenched ^ny workmen In its immediate vicinity. The number of men engaged in filling and handling the drums of gasoline was small but the severity of exposure was such as to give excellent opportunity for the detection of any effects which might result from gasoline absorption. These men were carefully exam! ;Od in a manner which will bo described later, and several types of laboratory data were obtained, including the lead content ; of the urine and faeces ("TWa.<*-** ' "" Xs7~(tai g ( r' (t u` -i.u U*. .4. ` V *'* '* ** ' 1 <^ fhortly after these examinations had been completed the refinery in question embarked upon the distribution of hthyl Gasoline. The latter was handled in the manner described auove for ordinary gasoline. Inas ouch as experimental evidence indi- / cated that the hazards of lead absorption from skin contact and mna.at^n of vapor from gasoline containing tetraethyl lead were t_oally negligiole, no fears were entertained as to the consequences of the additional factor of a low ccncentration of tetraethyl lead. Never theless* this constituted a unique situation from the point of view of severity of exposure. Therefore it was considered imperative to obtain Information which would show whether or not an appreciable lead absorp tion was occurring in the men. Accordingly, at the end of a period of six months, during which Ethyl Gasoline had been handled daily in this manner, the workmen so employed were examined, and samples of their excreta were obtained for analysis. In th^second group made up of v.venty-two men, there were ten who had been included in the first set of examinations. Except in the case of the barrel-fillers, comparable groups of subjects unexposed to the potential dangers of Ethyl Gasaline, were not obtained for study. At the time of the present study of filling station employees, tank wagon handlers of Ethyl Gasoline and garage mechanics, there was no area of the United States in which the selection of entirely unexposed subjects could be made with precision. The use of leaded gasoline had increased rapidly, so as to involve all parts of the country* Furthermore the employees of a large proportion of the major gasoline distributing companies were handling Ethyl Gasoline. Therefore it was necessary to rel on information obtained prior to the general distribu tion of Ethyl Gasoline, for comparative data on similar groups of subjects independent of the factor of leaded gasoline. Fortunately, such data were adequate. Furthermore, repeated observations had been made on the / same individuals under conditions of continuous exposure. These success ive findings furnish a means for the discovery of progressive effects of 3. Methods of Study '? The facts presented in 391 earlier chapters HlIt Til wnT inii would seem to establish the relationship between lead excretion and lead ab- Thus it seems certain that the most specific evidence of the magnitude of lead exposure and absorption is to be found in the rate of lead excretion, in which the faecal excretion is a measure of ingestion on the day preceding the collection of the sample, while the urinary excretion indicates the magnitude of lead absorption. Neverthele considering the importance of the matter at issue, we have considered it desirable to leave no stone untamed which might yield additional informa tion. Accordingly we have searched for clinical evidences of lead absorp tion with the same care that we have applied to the collection of accurat analytical data. The general clinical methods were similar to those employed by J. P* Leake and his associates and by ourselves in other investigations of the same question. A comprehensive neurological exam ination constituted the only significant addition to the prevfous tech nique. /> Care was taken to obtain all the information possible from each ( subject, and to recor'd such information in a uniform manner. Tor this reason cards for recording data were provided as reproduced below and the work was divided among four physicians each of whom carried odt the same type of observati**wan each subject. So far as possible quantitative information was obtained in the physical examination, but without the subordination of clinical judgment to the necessities of statistical comparability. Thus while it was recognized that a statistical study of all the data was desirable and necessary, sound clinical diagnostic methods as applied to individual cases were regarded as of greater impor tance, in determining whether or not any evidence of lead intoxication had appeared among the subjects. As an example of this point of view, each subject was tested for evidences of atrophy or muscular weakness 01 438 HISTORY SHEET No. - Name ` Marital Residence Examiners Initials - Age Race - - Color Ages Children Miscarriages Dato Birthplace Stage Other places lived in, with dates Place of Employment Length of present employment and previous employment at same work Type of work (exact description of nature and conditions) Previous Occupations Dates Previous Lead Hazards Painting Plumbing Carriage, Auto or Car Type Casting Smelting or Refining "Treating'' Refineries Storage Bax. Mfg. or Rep. Lead Burping Printing or Lithog. Mining 1 Foil, Solder, Babbit,Mfg. Dates Previous Lead Hazards Dates Brass Founding Soldering Enameling Paint Mfg. R ottery Glass Polishing Cut Glass White Lead Rubber Garage Telephone or Telegraph Rep. Automobile Ov/ner Gasoline Used Repair Work 's Prev'ous Illnesses with dates and exact descriptions (no leading questions) Tbc. Malaria Rheumatism Lues. Gc. scarlet Piph. Tonsillitis Frequent Colds Convulsions Heart Disease Significant Family History: Typhoid Asthma Remarks: HISTORY SHEET (cont) No. Examiner<3 Initials Sleep Hours in Bed Dreams Restful Bowel Movements Frequency Hour Tendency to Constipation Cathartics Tendency to Frequent Stools Date Disturbed Teeth Usual Weight General Health Brushing V-hen Best Weight Last Trip to Dentist Recent Loss Weight (seasonal?) Rate of Tiring Headaches Time Recent Change Eye Trouble (character and time of development) Taste in Mouth Character Time Pains in Joints Swelling of Joints Muscular Strength Cramps in Muscles Pains in Belly Character Frequency Appetite Different Meals Digestive Disturbances Nausea or Vomiting Skin Infant!on or Eruption General Hands Polyuria Nocturia Frequoncy Nervousness General Weakness Other Complaints Right or Left Handed Loss of Strength in Arms or Legs at any time Shooting pains Numbness or tingling Loss of Sensation 01 4 /'-t nu PHYSICAL E.XAMI RATIO?? SHEET To. Examiner's Init. General Appearance Nutrition Pulse Temperature Color of Skin (exact) Date Age Height Pos ture Musculature Blood Pressure (seated) Condition of Skin Weight Condition of Skin of Rands Cornea Sclera Nose Throat Glands TonsiIs Mucous Membranes Lars (structure) Teeth Lead ` 'ine (Apoearance and Location) Go ms Pyorrhoea Heart Apex Rate After 25 hops 2 minutes after R C I) r .s .d . x tof Lungs: K.I. - R. L. Chest Diagnosis s D.E * R y / L.LB. - ( Abd omen Liver hectum ' Spleen Genitalia Kidneys Upper Extremities Diagnosis and Remarks Lower Extremities (j | 4 4 s NEUROLOGICAL EG AM IN ATI-:) fl Cranial Nerves I Snell Examiner*9 Init. II Sight R - 15/ L - 15/ Condition Correction 111, IV, VI Extrinsic Eye Muscles Pupils Visual Field Reflexes V Motor Sensory VII VIII Audition R L IX, X, Xll Speech XI Neck Facies Equilibrium Swallowing Shoulders Tongue Jprer Extremities / Tonus ( Atrophy Ataxia Tremor Mus cul ar Power Dynamometer Stereognostic Epl CritiC "mmmrnm** Protopathic KinaesthetiC" Thermal Vibratory Nerve Trunk Tenderness Lower Extremities Reflexes Pharyngeal Biceps Triceps Radial Patellar Achilles Epigastric Abdominal Cremasteric Plantar Gait LABORATORY SHEET No. URINALYS IS: Examiner*s Initials Date Quantity Sp. G. Reaction (Methyl Red) Albumin (Heller's) Sugar (Pehlings) Acetone (Nitroprusside) Microscopic BLOcP: White Count Red Count Heat and Acetic Haemoglobin (Dare) Differential (ICO cells); Poly. Neutrophlles Poly. Eosinophiles Poly. Basophilea Lymphocytes Endothelial Large Mononuclear Transitional Abnormal Stippling per 50 fields Polychromesia y INALYTICAL EXAMINATION: Accurate st'ifLlllient of '.curs required for collection of; Urine Faeces Constipation Diarrhoea Cathartic (type) Wt. dish + dri3d faeces Wt. dish + ash Wt. dish Wt. dried faeces Wt. ash lead Mgs. Mgs./gram of ash Analysis No. URINE Volume c. c. Lead Mgs. Mgs./liter Analysis No. by palpation and by opposing the examiner's strength to that of the corresponding muscle group of the subject. But for the purposes of statistical comparison of a single neuro-muscular factor, the grip was tested by a hand dynamometer. (The same instrument was employed through out the tests.) Measurements of the blood pressure of each subject while seated, were made with a standard manometric apparatus. A fresh specimen of urine was obtained from each subject and examined at once for its reaction, the presence of albumin, and sugar. Microscopic examination of the urine and a test for acetone were carried out only when indicated by chemical abnormalities or / ( 014 4 4 l abo r at o r y sheet :i o. URINALYSIS: Examiner's Initials Date Quantity Sp. G. Heaction (Methyl Red) Albumin (Heller's) Sugar (Fehling's) Xcetone (Nitroprusside) Microscopic BLO ,>D: V/hite Count Red Count Heat and Acetic Haomoglobin (Dare) Differential (100 cells): Poly. Houtroohilss foly. Eosinophiles Poly. Basophilsa Lymphocytes Endothelial Large Mononuclear Transitional Abnormal Stippling per 50 fields Polychromasia M-.-m *t r ^ v ? j Accurate statement of C**i T* C j T ^ G 'Ll ** I" r' C* Urine Constipation Diarrhoea FAECES <1 w dish + dri3d faeces 771. dish + ash N't. dish v.t. dried faeces w t. ash lead I'gs. Mgs./gram of ash Analysis No. 101445 ^^ Fa sees Cathartic (typ URINE Volume c.c. Lead Mgs. Mgs./lite Analysis No. , by palpation and by opposing the examiner's strength, to that of the corresponding muscle group of the subject. Butyfor the purposes of statistical comparison of a single neuro-rauscular factor, the grip was tested by a hand dynamometer. (The same instrument was employed through out the tests.) Measurements of the blood pressure of each subject while seated, were made with a standard manometric apparatus. A fresh specimen of urine was obtained Irom each subject and examined at once for its reaction, the presence of albumin, and sugar. Macroscopic examination of the \irine and a test for acetone were carried out only when indicated by chemical abnormalities or / 014 4-6 by suggestive clinical findings. Erythrocyte, leucocyte and differential leucocyte counts ct >. di. C'.t~ were made as a routine^ only on the barrel-filler group of subjects. Otherwise, such procedures wore followed only when indicated for diagnostic purposes. Haemoglobin determinations were made on each subject by means of the Dare haemoglobinometer. A single instrument was employed for all observations, and all readings were made by the same ob server. Blood smears were made on all subjects, and were examined for stippling of the erythrocytes by the method previously des cribed. Samples of urine and faeces were obtained from the subjects , fc, 's for the determination of their lead content. The collection and. the analyses were carried out according to^the methods detailed in Chapter II. In a f^w instances no samples were obtainable. A further small number of Samples were lost in transit and in / process of analysis. With these few exceptions, the analytical results were obtained without difficulty. . -V U -L 4 / Ho caseintoxication was found among the subjects. In fact, no combination of symptoms and'physical findings was suggestive - of lead Intoxication. Such evidences of lead absorption as are common among lead workers were conspicuously absent, of special negative clinical importance v/ere the complete absence of lead line, the lack of significant microscopic blood changes (stippling)^ and the striking^infrequency of vague symptoms of ill health. /Tn this nl fnaM^ni1 any evidences of significant load ab sorption as a consequence of exposure to Ethyl Gasoline must be fjyi 014 4 7 sought in the data on the excretion of lead. The clinical and analytical data for the groups are pre sented in a series of tables, in which the factors are set down in the exact manner of the statistical study except as otherwise noted. / Table 5 shows the classification of the subjects according to the duration of their exposure to Ethyl Gasoline. One-half of the filling station attendants and a little less than half of the tank wagon handlers had been exposed for five or more years, while sixty-nine percent of the garage mechanics had repaired cars which used Ethyl Gasoline over a period of three years or more. Whether or not it has any bearing on the problem at issue, the occurrence of previous industrial lead exposure among the subjects may not be ignored. Information on this point obtained from the occupational histories is shovm in Table U . Here it may be seen that a large proportion of the subjects had been employed in trades which involved some opportunity for lead ab sorption, prior to their exposure to Ethyl Gasoline. None of the garage mechanics may be regarded as free from the possibility of lead expo^mjg^in their occupation, apart from the factor of Ethyl Gasoline. However, it may be assumed that few garage me chanics have more than a slight lead exposure in the course of their normal days work. Small jobs of soldering and painting, and the occasional repair of a storage battery have not produced a noticeable occurrence of lead intoxication among garage mechanic One tank wagon driver and eight garage mechanics had been employed at some previous time in hazardous lead trades, in which their exposure had not been severe either in quality or duration. 'tsrr r Period of Exposure In Years 1.1-0.25 0.5 1 2 3 4 5 6 Totals Distribution of Subjects According to Period "of Exposure to Ethyl Gasoline tjr-, ---------------- * --------------- Pilling Station Attends nts Number jy < y jy Tank '>* agon Handle rs Number < jy jy sy & Garage Mechanics Numbe: * ^ -Or Q J&' BdEXpl Fillers1^ Not Exposed to/ Ethyl Gas^iiarb Number jfnf 0V / '>) Barrel Fill* Exposed to Ethyl Gasoli Number < 4 16 18 82 i2 12 26 13 / A jy Jc jy *r 48 36 18 sy - 6n 16 28 23 41 48 19 38 16 32 98 49 22 11 12 6 .6 oA o) -0'/ / _ .... J ._ y jy y -e -c -o 10 18 56 100 6 12 50 100 73 201 100 sx or/ s\ \ 0 -o J 7 y ~o * 22 100 . -O A ' V* 2<s 01449 TABLE DISTRIBUTION OF SUBJECTS ACCORDING TO HISTORY OF PREVIOUS EXPOSURE TO LEAD OTHER THAN ETHYL GASOLINE v-jscrlption of Us ad Exposure Filling Sta tion Atten dants Number % None 20 36 uestlonable 8 14 Slight 28 50 oderate 3evere sr JT -4) Total 56 100 Tank Wa, on landlers Number f. Garage Mechanics Number # Barrel Fillers 3arrel Fii; lot Exposed to Exposed to Sthyl Gasoline Sthyl Gaso. Number % Number t 18 36 sr' 15 55 10 46 10 20 30 15 8 30 6 27 21 42 163 82 3 11 6 27 12 84 1 X & zf' JS' jy- 50 100 201 100 27 4 sy jr 100 22 jzr 10 vf - ^ . * : L ** A .` - hi. / *- -rnt. >' t- 1 C: 1 01450 The distribution of the subjects according to age, seen in Table "i ^ is significant only in that it demonstrates the inclu sion of widely varying age groups among the subjects under inves tigation. Tables X and rA represent the frequency of occurrence of certain subjective and objective abnormalities which are indicative of the presence of low grade intoxication. Amon^ the symptoms, attention should be called to the high incidence of headache among the garage mechanics* The histories clearly suggested carbon monoxide absorption as the background of this complaint. Irrita tion of the skin of the hands due to frequent contact with pe troleum products showed a high frequency of occurrence In all the groups. Pallor was most prominent In the garage mechanic group and in the barrel fillers not exposed to Ethyl Gasoline. The explanation of this s-ltueHsien in the latter group Is undoubtedly /'- < chrerrfco the fact that this group was examined in the sun er when />" the inhalation of gasoline vapor was at its height. These men showed a correlative diminution in haemoglobin and a high average stippling further indications of blood changes resulting from their .exposure. Comparison of the remaining items with the results of similar observations on various groups of subjects unexposed to Ethyl Gasoline fails to yield any significant irfoi ma ci'n . (Cf. Tables and on pages ft andEi-) In Tables t , : , and , the findings as regards blood pres haemoglobin of the bloody and stippling of the erythrocytes are recorded. No mean values were computed for the occurrence of stippling by reason of the high proportion of negative results. It may be seen from the tables that no sig nificance may be attached to variation In these matters In re- ri 01 451 TABLE 7 Distribution of Subjects According to Age Age In Years Filling Station Attendants Number a? Tank Wa gon Handlers Humber * Garage Mechanics Humber it IS-19 sf or or 94 JO-24 3 5 0"' &r 32 16 35-29 12 21 15 30 33 17 0-34 12 21 7 14 34 17 '5-59 5 9 10 20 42 21 24 5 10 26 13 -5-49 5 9 5 10 11 5 -0-34 -." -59 : 0-n-r 5-o9 47 7 13 6 11 'V sr' 3684 1 2 4 - Oi. 3 6 r2 i 1 o / & AT Jotal 56 100 50 100 201 100 Barrel Fillers Hot, Exposed to Ethyl Gasoline Nu -,ber Barrel Fil Exposed to Ethyl Gaso Number 4.*?f P"" O' AT CK 1 5 6 23 29 5 19 6 27 5 19 o-* 23 29 7 31 14 2S 14 o0 -O ,0 Vrs. i 26 100 00 15 15 22 100 Jean i 1 .t o cable -ryor of "ear 40.3 + 1.2 33.0 + 1.1 i 34.3 + 0*5 - \ 3,7.9 39.1 i + 1.2 +1.3 Standard Oeviatior 13.07 11.28 9.83 3.73 9.34 TABLE Distribution of Subjects According to Certain Subjective Abnormalities Type of 56 50 Pilling StatJ on Tank Wagon Attendants Handlers Abnormality Number ,.4. Number < scent Loss :f Weight 3 6 24 201 Garage Mechanics Numbe 74 27 Barrel Fillers Not Exposed to Ethyl Gasoline Number y sr / 22 Barrel r'ille; Exposed to Ethyl Gasolii Number < O'" jzr' Increased /ondency to ~ -.1 *--> - f*a r-, .a 1 n 1 uO* 3 4 2 7 XK <<r' "roquent 'eadache 6 10 2 4 V * 15 2 7 15 Iocasj onal bdcminal 'r-'mio 2 4 2 4 12 6 1 4 15 Iccasional "i restive Mo turbance //casional euritic mo to s 3 "3 * 5 ,5 ow 4 4 2 1 4 sr 73 P" -3" 15 15 'orr General 'ealth -*T & .0' rsJ\- - 1 1 (T -0 0 .a TABLE -1 Distribution of Subjects According to Certain Objective Abnormalities. Type of Filling Station Tank Wagon Garage Attendants Handlers Mechanics onormality Number Number < Number < nder- .ztrition 4 6 2 4 84 al lor 2 4 ]2 4 23 11 rritation f Skin of znds 11 20 12 24 56 28 3a d ine 0" 0 jy O' Or' erve Trunk ?nderneas 6 n 17 34 17 8 remora 20 .36 21 42 71 35 onsory is turban 's 1 2 3 6 *A* 2 tens or ires is 1 o 3 6 1 1 trophy of tper Extrerr zies 1 2 4 3 914 jncrnali tie s ' Visual ield 2 4 12 | i e- ! ,o rinary cidity 20 39 15 33 92 45 Ibuminuria 0 0 49 63 Barrel Fillers Not Exposed to Ethyl Gas.line Number >0 4 15 8 30 16 60 jy -O' 3 11 8 39 r> cr jy jy sy i ..o' i o 14 AT jy Barrel Filler Exposed to Ethyl Gas dint Number % 2 10 2 10 12 54 jy jy l5 9 41 2 ,10 ( JOT J&r 15 ' 2 ' 10 16 73 jy yr TABLE 10 Distribution of Subjects According to Systolic Blood Pressure 3lood Pressure Headings Pilling Station Tank toagon Attendants Handlers Number irf Number if /: Garage Mechanics Number Barrel Fillers Barrel. pii: Number < Number 80-39 ,0 jar sy 11 O' .0 0- 90-99 1 2 o- jar' 4 2 >o- s'o 1 c 100-109 3 5 24 16 8 s& Jar' 110-119 10 18 16 32 52 26 4 15 5 22 120-129 18 32 10 20 62 30 7 26 7 32 130-139 9 16 7 14 36 18 8 30 4 18 140-149 150-159 7 12 .4 8 18 9 5 13 4 18 2 4 o 4 5 21 4 -0- 160-169 3 6 4 22 7 -Or -O' 170-179 130-189 o Information Total 1 ' / 3 2 4 5 56 100 JJ .or O' -Q X)' 2 4 2 10 4 ____ .1 1 0 50 100 201 10 3 27 JOT o0 100 1 ,-G" 22 5 -O' -0*' 100 *f n Probable ^rror jf Mean Standard deviation 130.1 1.7 17.86 T .l o O .4 j 1.9 19.30 125.7; 1 1 0.7 i 15.10i iO-i.3 il.8 1 13.59 .'.29.1 1 2.3 15.86 nrO 01 455 TABLE Distribution of Subjects According to Haemoglobin in Blood lemoglobinometer Pilling Statior Tank *'agon Attendants Handlers ?ading (Dare) Number iif' Numbei s' 50 - 67 & er" 1 2 Garage Barrel Fillers Barrel Fill ?,{echanics Not Exposed to Exposed to Ethyl Gasoline Ethyl Gasoi Number onf Number .W Number sy er 9 33 15 63 - 75 15 27 4 8 13 6 12 44 15 76 - 83 ' 21 37 12 24 77 39 4 15 8 35 34 - 91 15 27 27 54 92 46 1 4 11 50 92 - 99 Information 59 & Jd' 5 10 15 7 .er 1 24 O1 er 1 5 4 jar otal 56 100 50 100 201 io<!) 27 100 22 100 s "ean 30 9* 85.0* 84.5*- 71.1* 83 .3* frobable error of Fean + 0.67 + 0.59 + 0.24 + 0.92 + 0. y 1 standard deviation 7.39 6.1- 5.09 6.98 6.34 * All means calculated on a wider grouping of readings. i 01 4 E Distribution of Subjects According to Stippling of Erythrocytes lumber of jtippled 'ells Per ;Q Fields 0 1 2-5 6-10 11-20 21-32 :>tnl Filling Station ri'ank Wagon Garage Attendants Handlers Mechanics Number eAi Number 4. Number 4 Barrel Fillers Not Exposed to Ethyl Gasoline Number 36 64 33 66 159 79 7 26 6 11 a 16 19 9 4 6 11 5 10 17 8 6 22 35 24 533 11 35 12 1 14 15 24 12 XT' & 6 22 56 100 50 100 201 100 27 100 Barrel FilJ Exposed to Ethyl Gaso] Number 4 21 95 15 ' J0 & -6 jer 0 sy -0 22 10 lation to Ethyl Gasoline exposure, since practically all the findings are within normal limits. In the case of the systolic blood pressure, which is used here only as a general moans of pointing out the probable existence of vascular disease, the high readings are sharply correlated with age, and hence have no sig- p. v ? CI`w ni^icance. The low results are of no frequency than is common among corresponding groups of presumably normal persons. The haemoglobin determinations show only a high frequency of low results among the barrel-fillers unexposed to Ethyl Gasoline, as previously pointed out. Likewise the only point of interest in Table iar the relatively high results among these same barrel fillers. Apparently, exposure to gasoline vapors may produce blood changes, including the appearance of stippling. Tables and record the observations on the strength of the grip of the left hand and right hand, respectively, of the subjects. The frequencies and the means do not show any very striking differences between the groups, except^fcu--irgatg that the barrel fillers as a whole, gave a somewhat weaker response to the test. The facts obtained from the analysis of t:he excreta of the subjects ane jDg^gented In Tablss ,, , - , and . A survey of the tabulated 3'esults shows that a few high results are scattered - irregularly through the data.----- - -- ~*Where these occur in faecal samples it may be assumed that they have resulted either from contamination of the sample or from the ingestion of unusual amouts of lead with food material, and that they have no necessary or probable relationship to occupational lead exposure. Accordingly the inclusion of such findings in the computation of mean values increases appreciably the probable error 01 458 TABLE O .2 Distribution of Subjects According to Strength of Grip of Left Hand Hand Filling Station Tank Wagon Attendants Dynamomete: i Handlers Heading Number 6f /J Number 4 50-59 e< 2 4 50-69 1 2 2 4 Garage ?iechanics Number <4. 42 31 Barrel Fillers barrel Fills Not Exposed to Expo sed to ^thyl Gasoline Ethyl Gasol3 Number Number 9^ & -e" 5 19 2 9 70-79 7 12 2 4 8 4 2 7 3 14 80-89 5 9 3 6 30 15 4 15 2 9 90-99 7 12 13 26 47 23 3 11 7 32 i00-109 10 13 6 12 42 21 6 22 3 14 110-119 2 A o 4 20 10 2 7 4 18 120-129 1 2 7 14 25 12 O' S' 1 4 130-139 140-149 1 150-159 160-169 y'r\ .. 0- No Informstior3 t Octal | 02 56 O O' Qy 39 ICO 00 o 12 .0"' .0 1 5 5 1 2 10 20 ! 9 50 100 I 001 31 5 O' 1 4 Or'" ^ OT". 'Sf V / 1 i! | 41 ___ i 100! 4 -- - 27 1 I ?5 - --* -~ --- i p.00 xT" i ; 22 sr *r j st 07 cr 100 v.ean Probable Error of Standard Deviation 95.0 1.9 16.63 101.5 +2.4 22.75 102.9 + 0.9 19.37 21.1 + 2.7 19.05 ! 95.0 + 2.4 16.51 TABLE /4 Distribution of Subjects According to Strength of Grip of Light Hand Hand Pilling Station Tank Wagon Garage Attendants Handlers Mechanics Dynamouetei Heading Number Number Number <st 50-59 XT & JQ- P-- 60-69 0 J2r JSr- 1 1 70-79 fr 2 43 2 30-89 35 4 8 9 4 90-99 3 14 6 12 29 14 r:o-ic9 110-119 120-129 48 7 12 59 7 14 40 5 10 28 6 12 33 20 14 16 130-139 110-149 3. O La 150-159 160-169 ^ ^0 No Inf ormatio: 1 23 Total 56 5 .. 4 O ! -0 ! 41 ICO 5 I2 /O 1 10 1 50 10 22 - ii 4' 19 10 4 7, 3 21 1 20 9 4 100 201 100 Barrel Fillers Not Exposed to Ethyl Gasoline Number Barrel Pil; Exposed to Ethyl Gaso Number t. 27 A O' 1 4 3 11 -or" K 1 4 7 3Z 4 15 2 9 3 il 2 9 5 13 4 ie 3 ii 3 14 14 29 14 14 JO" S> -0 .0 00 O -e 4 15 i 27 ioo ! oo -0 10 Mean 1-------------------------------112.6 Probable Error of Mean + 2.2 Standard Deviation 18.43 114.0 +2.4 22.34 116.3 +0.9 19.58 101.9 +3.3 23.30 105.0 +3.0 20.89 01 if n Distribution of Subjects According to Lead Found in Faeces Milligrams of Lead Per Sample of Faeces 7 - 0.079 '.08- 0.159 '.16- 0.239 .24- 0.319 .32- 0.399 .40- 0.479 .48- 0.559 .56- 0.639 * .34- 0.719 .72- 0.799 .30- 0.879 .83- 0.959 .96- 1.039 .04-1.119 .12- 1.199 .80- 4- 0 nformation otal can nobablo nror of aan tandard eviatinn Filling Station Attend ants Tank Wagon Handlers Garage Mechanics j Barrel Fillers Not Exposed to Ethyl Gasoline j Barrel Fil Exposed tc Ethyl Gaso Number 6 5 12 11 9 21 Number | '' Number -i Number 1 o 5 3 /L 4 8 26 13 ' 4 4 3 33 17 7 V 7 Number 0 2 9 if A 0 9 41 47 i 8 ! 14 6 12 85 12 6 12 23 14 3 . // 4 /r 5 1 25 5 2 2 l -o" j xj ! 11 i ! if '0 \y i ..O' 2-.- 13 58 |4 i4 :2 ! -0 1 ; i ,-2 * ! ,0 . ! 0_ C .<7JLI \ 4 2 100 2 4 17 ! 5 10 j 13 i n 4i 8 i' 1:217 i! x) > 7 ! i! i .3" 1 J6 j 3 ! (I , ,Q- ; .O' i 2 I; 1 lj ! ;2 ! 2" : 0 3 j J I .0 j* j 1* 1 8 O n-v- ; !| '17 1 34 I 13 ! 50 ! 100 201 9 6 r (4 j f3 13 i j2 i| 11 1 : !1 i :3 | -O' ! i ;3 !! j6 i j100 3l .? l ! : 0 O' > ' & 27 !i _ 4. i i M 2 1 0 cr 0 Q&1 0 _____<5i_- ___ j ! .-</ ; 12 ! `i j,- ,- j ; <0 ioo ! 0 0 0 i* 0 9<) Ut 9 5 or 0 5 -0 cr 5 O'" 100 C.253 r 0.860 0.379 0.380 0.238 +0.018 0.169 +0.023 +0.012 0.197 i----;-0--.-2-4--5---- +0.037 0.266 j } +0.024 0.160 TABLE /t <9* Distribution of Subjects According to Lead in Milligrams per Gram A3h of Faeces Milligrams of Lead Per Gram of Ash Filling Station Attendants Number Tank Wagon Handlers Numb ai . d Garage Mechanics Barrel Fillers Not Exposed to Ethyl Gasoline Barrel Fll Exposed to Ethyl Oaso. Number Number of Nvmbe: : 0-0.039 10 18 24 521 4 P a. 04-C. 079 14 24 16 32 51 25 9 33 7 3J 0.03-0.119 9 16 48 54 27 7 26 8 36 0.12-0.159 0.16-0.199 0.20-0.239 ^.04-0.279 `'.28-0.319 : .32-0.359 .35-0.399 :. 40-0.439 : .44-0.479 0.48-0.519 4 2 1 1 1 0 0 0 0 0 8 36 36 13 3 11 29 4 3 6 | 18 9 2 7 3 14 1 2 1 21 8 4 1 4 29 2 2 12 0| 0 j j 4 21 4 f"~"---- ----- Ow J* JZ' 0 J 0 9 { 6 0 0Q 111 4 0i <* 0 00 6T Jd ' & PT 0 o' 0 12 0 00 1 l'l.. 0 60 P /O 1 2 / 520 dT P 0 7 0 ( Q Q- d 06 n. 00 3.56-0.599 0.01-0.673 3.'"0- + ! :;o Tnf ormatior Total 0 0 1-r 13 56 0 i2 c xy -O' l# 1 22 17 | 31 100 I 50 1 100 <r Jd 0 0 00 3! 1 i\ 0 i0 <) 0I 0 ) i-> i 1 0 0 0! 0 f 13 j 6 0 00 201 t 1001 27 100 oo 100 Me an 0.087 0.120 0.123** 0.131 0.137 -------------1-----------i 0 .113 Probable -rror of Mean Standard JDevia tion 1 0.007 0.065 - 0.014 0.115 ^ 0.004--* - 0.005 0.074**' 0.100 0.014 0.106 1 0. 007 i ; 1 0.052 *Excluded in Calculation .of Bba@ "] A 5'/ ** Calculated aTter exclusion of three .. ------- ~ ~,`"4----------- TABLE / 7 Distribution of Subjects According to Milligrams of Lead Per Liter of Urine '`illigrams ".'2 Lead Per Liter of Urine Pilling Station Attendants Number ,4 Tank Wagon Handlers Number /J Garage Mechanics Number < Barrel Fillers Not Exposed to Ethyl Gasoline Number Barrel Pill Exposed to Gasoline Number t 0-0.039 32 _n 72 . 45 72 5 27 8 35 .04-0.079 15 .. 27 ia 35 . . 75 . 38 1 5 80 in 45 0.03-0.119 .... 13 . _ 23 4 ... 3 34 .17 5 1A 2 Q ".12-0.159 3 .....5 ....1..... . 2 . In ._.....n n . ... ......1, 5 .16-0.199 5 K, 1..... o .5 o .2 n .. n. fl 20-0.239 _____1_____ 1 :.24-0.279 ; 0 0 .. fy n 3 1. l o ._ . 3 1 .28-0.319 i .02-0.359 ; ! .06-0.399 1 0 0 O 0 ... 0 .... . * 0. . 1 . . 2 ____ 3 12 4 1 1 .0- ___au. _____1____1_ ----.-0--0-----0---.-4--3a9z-pi .44-0.479 ! 0 0 _____ 0___ n. 0 1 0 / CV 0 1 .. 1 1, 1 '.48-0.579 . . 0 0 1 on ro i + :;o In forma tier. Total lr~* r* Lj lr--r ! i 1 ! r\ , .1 __ 10 j TO 56 1 100 ' \ 1 50 ! 100 ! i ___ ! 3 "r1 f 3 *4 201! led .. n . _ o._ . ' . 0_ . 0 0 r\ o O o 27 . .. n n 0 ...0 ..... o ... i___ _____ \ 1n _ ! j0 j 1 |0 _ * 100 1 n Cl ... _ i / 0 .1 0 c 0 .0.. 0o h. . . 0 o ..0 00 1.___ 5 22 1 100 Mean 0.071 0.039 0.086 Probable Error of 'lean 0.005 0.011 n.oc4 Standard Deviation . 0.050 0.099 0.079 * Mdan calculated on a wider grouping of findings Excluded in calculation of means 0.058" 0.009 0.071 0^ 4 0 3 0.052 0.004 0.030 of the means. Nevertheless, such results have been recorded, and have been Included In the calculations unless otherwise specifically noted in the tables. Where a result has been excluded it has been for the obvious purpose of eliminating a finding which has no possible relation to the problem at issue. In the case of the urine samples, aberrant results are of rare occurrence, as would be expected. On the other hand contamination of an occasional sample during the process of collection is apparently unavoidable, despite the most careful ins true tioiv. of the subjects. This is not remarkable when the ubiquity of lead compounds is appreciated, and when the lack of understanding of chemical cleanliness on the part of the subjects is taken into account. Thuo when a ouitataly-large-.cample irmilalne- qfl Viale Tn* 1 1 i flr" ITT--" f ''i ? ftd pftr 1 certain that...lend hntw.been n ft-n-t, iMsleeo--i^ne--yub^^ei;,,'hH^,gbgcrbed-^VTrry-->^vgrgg'*>g.TBm:ri t a- -&& lea4 , The analytical results serve to classify the various groups7 of subjects as distinctly outside the hazardous lead trades. At first glance, the mean values for the lead content of the faeces of filling station employees, tank wagon handlers and garage mechanics seem high, t < '-v '. v.KC as compared to normal persons occupational lead exposure. (Of. page ) On the other hand, the small group of barrel fillers who were not exposed to Ethyl Gasoline, and who had no other occupa tional lead exposure at the time of the examinations, show similarly high findings. Furthermore when the faecal lead is expressed in quantitatively comparable terms, in mil igrams per gram of ash, the apparently high results tend to lose their significance. Finally, the previous data have amply demonstrated the impossibility of drawing exact conclusions as to the magnitude of lead absorption, I 0146 4 4--- on the basis of the faecal excretion of lead-. Thus it is necessary to resort to the study of the urinary excretion for such information. As Judged from thbr standard, the groups fall into the category of persons lacking occupational exposure to lead compounds. A special significance derives from the failure of the barrel fillers to show any increase in their lead excretion as a consequence of their exposure to Ethyl Gasoline. Not only do the two groups fail to differentiate themselves, from the point of view of lead excretion, but it is equally true that no single individual in the groups can be differentiated. Of the ten persons who were examined prior to exposure to Ethyl Gasoline, and again after six months exposure to Ethyl Gasoline, no one person shows an increase in his rate of lead excretion. This ;-'-W ^ can be interpreted cfs meaning that there was no significant lead absorption as a consequence of this severe exposure. Thus> / it seems quite clear, that the inability of animals to absorb measurable amounts of tetraethyl lead out of gasoline in dilute solution, (1 part per thousand by volume or lacs) is shared by man. In view"n,The important conclusions of the above paragraphs, indicating the completely negative character of the findings, it . is only proper to present observations of a strictly comparable character on groups of subjects similar to those employed in the present investigation, in every matter save ^hat of exposure to Ethyl Gasoline. Accordingly.TaWt/- IT>1 ***<dL4v*. show the results obtained ih 1927, in the study of groups or persons who had not been exposed to the conditions associated with the use of Ethyl Gasoli'e . The medical student group differs from that aprearing in Tables ^ 1 01465 TABLE !' Distribution According to Age of Groups of Subjects Not Exposed To Ethyl Gasoline, Examined in 1927 Age In Years 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-^64 y 65-69 / 70-74 otal Medical Students Number 11 51 9 0 0 0 0 0 0 0 0 0, 71 if 15 72 13 0 0 0 0 0 0 0 0 6 100 : le an Probable Error Of Mean Standard Deviation \ 22 .3 +0 .2 2 .3 mm*. Filling Station Attendants and Tank Wagon Handlers Number i4 11 18 16 23 20 16 14 11 10 13 11 10 9 10 9 54 44 33 114 - 100 37.5 +0.8 ,12.54 Garage Mechanics Number 2 2 12 12 2 4 1 0 0 0 0 6 35 .4 6 6 34 34 6 11 3 -o . 0 0 o o 100 31.2 +0.8 6.69 TABLE - Distribution According to Certuin Subjective Abnormalities of Groups of Subjects Not Exposed to Ethyl Gasoline - Examined in 1927. Type of Abnormality ocent Loss )f Weight Increased >ndency to ''atigue )ccasional oadache )ccasional abdominal ' rcmo Occasional digestive is turban ce occasional leuritic Symptoms oor General ealth 71 Medical Students Number 7 10 9 13 15 21 11 11 - Q 23 69 Pilling Staten At ` endtints Number 42 Tank Wagon Handlers Number irf) 11 25 12 17 5 12 17 25 7 17 23 0-" 8 12 57 34 10 ( 2 24 ) / 5 00 35 Garage Mechanics Number jf 5 14 5 14 18 51 * 4 12 13 01 467 TABLE * 0 Distribution According to Certain Objective Abnormalities of Groups of Subjects Not Exposed to Ethyl Gasoline - Examined in 1927 Type of 71 Medical Students Abnormality Number f Under-nutrition 7 10 Pallor 1 1 Irritation "'f CVjn ryf Hand s Or -er pead Lins J>- -0" Tremors 2 3 Sensory Disturbances Grinary Acidity 3 / 7' i 4 10 Albuminuria 1/ 1 69 Pilling Station Attendants Number irf' 42 Tank Wagon Handlers Number 35 Garage Mechanics Number -f 13 19 34 00 -0" a o- "0" e- 23 -0 -0' 9 13 9 13 * 34 .3 4 sy J0-" 4 10 P- 25 16 38 37 4 3 a- l 8 3 n 9 0-- 3 23 9 \li 014 6 8 TABLE > S'3 Distribution According to Systolic Blood Pressure of Groups of Subjects Not Exposed to Ethyl Gasoline, Examined in 1927 Blood Pressure Medical Students Read ings Number 100-109 1 l 110-119 22 31 120-129 23 33 130-139 17 24 140-149 7 10 150-159 1 1 160-169 0 0 170-1*79 0 0 '130-189 0 0 190-199 0 0 20C-2C9 0 0 210-219 0 0 220-229 0 0 ' 230-239 0 0 Total 71 -- >460 Pilling Station Attendants and Tank Wagon Handlers Number if 2 O* 15 13 32 28 29 25 15 13 97 22 11 11 33 33 11 JO- JO- 11 114 100 Garage Mechanics Number 6 14 7 5 3 0 0 0 0 0 0 0 0 35 < JSr- 17 40 20 14 9 0 0 0 0( 0 0 0 d 100 Mean Probable Error of Mean Standard Deviation 125.9 138.2 0.8 10.20 1.5 23.45 'per 1 01469 129.8 1 1.3 10.98 TABLE y "f Distribution According to Haemoglobin of Blood of Groups of Subjects Hot Exposed to Ethyl Gasoline, Examined in 1927 Haemoglobinometer Beading (Dare) 60-64 66-69 70-74 75-79 30-84 35-39 90-94 95-99 100-104 lr5-109 Total Medical Students Number 1 1 0"' 3 10 21 17 11 5 1 70 < 1 1 -0' 4 15 30 25 16 7 1 100 Pilling Station Attendants and Tank ^agon Handlers Number * AT 11 98 12 11 17 16 43 40 15 14 98 22 9" / 108 / 100 ( Garage Mechanics Number .0o1 2 6 12 * 10 3 '0 JQr 34 0 O 3 S 18 35 29 9 0 10c Mean Probable Error Of Kean Standard Deviation 89.8 "+0.6 7.78 86.0 + 0.5 7.15 83.0 + 0.7 5.73 01 4:/ nV Distribution According to Lead Pound in Faeces of Groups of Subjects Not Exposed to Ethyl Gasoline, Examined in 1927 Milligrams of Lead Medical Students Per Sample of Faeces Number 0 - 0.079____________ ... 17 ..... SUQ3. - 0.159 15 0.16 - 0.239 19 25 22 27 0.319____________ C.,.3,2- 0.593____________ Q.40 - 0.479____________ 6 ______ o 9 5 3 0.49 - 0.559 0.56 - 0.639 0.64 - 0.719 23 11 11 0.72 - 0.799 e -0" 0.80 - 0.879 0.38 - 0.959 i1 i1 0.96 - 1.039 1.04 - 1.119 1.12 - 1.199 1.20 + Total l l a70 -O' 1 1 U0 100 Pilling Station Attendants Number 14 20 14 20 18 25 7 10 7 10 68 11 g' -0- 11 -O 11 0 o- O'- -er" .0 e x>-' -e | 3-" 4 ' 72 100 Garage Mechanics Number 5 7 2 2 3 2 1 0 0 0 0 1 0 o Q 3* 2610C 19 27 8 5 11 o 4 0 0 0. /" w /4c 0 Q: O' 11 Mean Probable Error of Mean 0.232 -U - 0.019 Standard deviation 0.0236 ^'-Excluded in calculation of means 0.197 -0.013 0.159 0.235 4* 0.029 + 0.205 TABLE Distributi on According to Milligrams of Load oer Gram i^sb. of Faeces Of Groups of Subjects Not Exposed to Ethyl Gasoline, Examined in 1927 Milligrams of Lead Per Gram of Ash C - 0.049 0,05 - 0.099 0.10 - 0.149 C.15 - 0.199 C.20 - 0.249 0.25 - 0.299 0.30 - 0.349 0.35 - 0.399 0.40 - 0.449 0.55 - 0.599 0.65 - 0.699 1.50 - + Total Medical Students Number ef Filling Station Attendants Number . sf 29 48 29 41 16 27 26 31 9 15 35 1 2- 8 11 46 0 -w''~ 9 0i $0 i 06 11 11 JeT' i 2- 11 i 2- J 0 J 'J 0 0 /0 0 00 2** 2 60 100 71 100 Garage Mechanics Number 12 6 1 2 1 1 1 0 0 0 2 Or'' 26 46 23 4- a 4- 440 \ 0 6 8 G-" 100 Mean 0.079* 0.077^- * 's 0.085 & 0.131 Probable. Error of bean -0.008 - 0.006 .,, . - 0.012 Q - 0.023 Standard Deviation 0.094 0.071 0.085 0.177 * Me an Calculated on a wider grouping of Findings Excluded in Calculation of Mean Calculated after exclusion of two results over 0.65 milligrams TABLE p. L Distribution According to Milligrams of Lead Per Liter of Urine of Groups Of Subjects Not Exposed to Ethyl Gasoline, Examined in 1927 Milligrams of Lead Per Liter of Lrine 0.- 0.029 0.03 - 0.059 0.06 - 0.089 0.09 - 0.119 0.12 - 0.149 0.15 - 0.179 0.13 - 0.209 0.21 - 0.239 0.24 - 0.269 0.27 - 0.299 y'0.45^ - 0.479 1 " IW ' " 0.54 - 0.509 0.66 - 0.689 1.00 - + Total ' Medical Students Number 11 22 ... 16 10 17 ...... 3.4..... 25 15 1 1+ 1 1+ 1 1+ 1 1+ Or v '1 .0 1+ -O' O' c 1* 1+ o0 ' 65 ICO Filling Station Attendants Numbsr *4 Garage Mechanics Number '1 ........ 11 20 . 15 ....... ...28 _ . a 4 31 15 _ - 17........ 24......... 68 ....... _4........ ..... 6............ 34 _.... - -5.. . _ 7 0 0 .. 0i 0Q 1 1+ 5 19 28 5 ... _ . . 19 0 / 0 A.......... . .0 0 0. i4 00 ! 00 1* 1+ 1+ 0 6 0 1 0 3* 4 i* 4 72 100 26 100 Mean 0.078 robable Error of ean 0.007. tandard Deviation 0.089 ^Excluded incalculation of means 0.081 0.006 0.069 0.077 0.008 0.059 It'! 01 474 ^7 7.111 and XIV, in Chapter 111, only in that those who have had some * degree of previous occupational lead exposure are included. For the second group, filling station attendants and hulk handlers of t . V, ordinary gasoline are Champed.tegutHUK;in order to make a large group for statistical purposes. Unfortunately, no analytical data are available in the case of the bulk handlers of gasoline, because of their unwillingness to cooperate in the collection of samples. There fore the analytical findings relate only to filling station attendants as indicated in the tables. The control garage mechanic group is made up of only a small number of men carefully selected in 1126 as lacking any exposure to Ethyl Gasoline. The rigid requirements in the latter regard introduced considerable difficulty into the problem of obtaining cooperative subjects. No explanatory comments are required, since the tables . ' present the observed facts^ "It should be pointed out that the ob servations recorded in these tables were made by the sanje persons whocollected the data on the exposed subjects previously described. The clinical methods employed in the two instances were substantially the same, while the analytical methods were practically identical. Tablesummarizes the mean values for all the groups c.f exposed and unexposed persons, in such matters as would seem to have special significance. (Since the frequencies of occurrence cf stippling do not lend themselves to computation of mean values, this . comparison of important factvmust be made from the tables of distri- ~A /N ;\ .UvCu1-*3 bution.) Comparison of the means a striking lack of statis tical differentiation of the groups. The medical students show a significantly. difference in age, but in no othdr factor. The barrel s fillers not exposed to Ethyl Gasoline show a significantly low haemoglobin content of their blood, as previously pointed out.. The 01 475 c-r X hJ ft 3 *4 0 3 --> ta i--1 fct a* *t 3 ta cr ft OO ft 3 ft h"* 3 3 cr O 33 f4t CT *1 -3 ft ft XM OT) - O >TJ CO CO H* O ft ft CL M H* CD 3 c+ 3 OU --------------j. I +W ft tO Li ft 1+ 03 H-3 ro <o 3 23 X P ft 3 X cr O CO 3> 3* cr 3 ft O Q g <; a to ft ta r*j txt+j ro to 3ft a 2 cf <5 cl x' to c'3 ao to to t=i O X Q O 3* 3m ft o a 3ffl* 33ft +34*3oft ft* tO 3 0) to ct 3 O *-* o 4. ft -4 to t+ O* 0f 4t 03 03 I + Cj 3 O ft* (DH ro I 4- 03 l-> 03 - a* to ro to r.M ft* I + 03 ft* ft CD W | 4- ro O 03 -4 -4 . ft* | +to ft* tO 03 03 | + 03 m a t0 ft I + 03 O OJ to c m i + -4 O ft* t to ft* ro '+CO O ft tfot 03 I+ 03 O CO -4 O 1+03 O 03 ' 03 O to oc cd oo ** O 03 03 CD -4 O 1+ oo O 03 ft -4 to tO 1+ oo * O ro 0CO3 to 03 1+ .? ? Oto 0033 03 O I+ 1+ oo O ft1 ft Cm ft -4 1+ co O 03 03 ft* 1+ oo O ft* to 03, 03 ft !+ oo ** OM to o co C CD + tO oo oo toOo0n3 1+ oo oa O CD ft 03 1+ oo oo O4 CD 4 1+ oo t oo ft CD ft to tO CO to -4 CO o 03 I-1 03 Ol o | +ft ft* O tO 03 C~3 oo r23s as "t j 3 a. 3 cT ta--.1 3 C3 3 3 OQ O ta sr CD W ft) X ct P 3* 3s 0 ct-CW C23T CT &* o 3 ft ftj 3 o a? X 1 3 ft=: ss ;s TO ;>. s ct a g v t , (- t-* ft ci :) X ffi o o-a t--1 & ? VJ CO CO O CT U ft a c !_ Q, M3 Cta O o 3 . Vi CT 4 CO | +03 O -4 03 Ol I + to O CO to 03 01 c <3 O cr to i-M o 3 o t-* CT +3 ta CT H> O 3 O Kj > CR to 3 ft 03 ft o -4 ft 1. + M03 M CD or ro 03 OO OJ to 4 Io+ o o to 0f3t 0O0l I +03 o o * 03 O oo O ft M tO 03 -4 oo o <5 4 -4 |+ t oo *% oc O4 03 4 t+ OO oo 0 -4 01 3--1 1+ oo co 001 0M3 1+ to O Ol CD cO I +03 O to 0 03 "3 01 01 ta ta CT a O e J ft? O ft) M O o a "TS'SJ a 33 ^3 H* O 3 ft3 C4 M aO O' I+ oo c to M 03 tO JO t+ oo oc d *4 I+ OO * oo C -4 4 03 W O D tr 33 ft oi a* M 3 M to-t, mO ft? to M ft ft 34 3 f3t ft O3 O 233 to ro 0^3 ta to fOt fot ft *+ 23 c 3 ft ft 3 OCT 3 33 ft? M 01 a 7 f3--t*1 *> O c tmcOrrn o H+J O' O o a 3 CT ta /TABLE 2 Summary o f Mean V a lu e s o f Age, S y s to lic . B lo n d P re s s u re , TTnc;,io{ lo b ln , and E x c r e tio n o f Lead In Faeces and U rin e , fo r V arious fir'ou": o f S u b je c ts . o' mean lead content per sample of faeces shows certain statistically significant variations withi- the groups^but no actual can be attributed to these differences in view of the variability in the size of the faecal samples. When the latter factor is corrected by expressing the lead irs the faeces in relation to the quantity of ash, the variability of the groups becomes statistically insignificant. It has been Intimated previously that some significance may oe attached to the fact that a considerable number of the subjects had been exposed to lead compounds in previous occupations. Likewise the handling of lead compounds other than leaded gasoline and its deposits on motor parts and elsewhere, might be expected g o have some influence upon the lead absorption of the garage mechanic. As a means of ascertaining the significance of these matters, the analytical results^ derived from two small groups of persons whose occupational histories failed to give evidence of previous lead exposure, were subjected to study. Table Is has shown the distribution of the subjects, as to previous occupational lead exposure. Table presents the mean valuesjfor^jthe excretion of these subjects as separate group-s- and in combination. The results are seen to be slightly lower, but no significant statistical differences'hae*/resulted from the exclusion of the previously exposed subjects. Considering the rate at which large quantities of lead have been shown to be eliminated from the body, the effects of previous slight or moderate exposure to lead, would not be expected to siwithemselves in an increased excretion after the lapse of years. Nevertheless it i3 of some in terest and importance to establish the facts in the matter. ni 477 TAELE :s Mean Values of Lead in Faeces and Urine of Filling Station Attendants and Tank Wagon Handlers, Exposed to Ethyl Gasoline, Excluding All Results Obtained on Persons With Other Industrial Exposure to Lead Compounds. Lead in Milligrams In Single Sample of Faeces Filling Station Attendants Exposed to Ethyl Gasoline 0,338 + 0.043 Tank Wagon Combined Handlers Filling Station Attendar Exposed to and Ethyl Gasoline Tank Wagon Handlers 0.277 + 0.035 0*330 + 0*030 Lead in Milligrams Per 1-ram Ash in Faeces 0.069 + 0.009 0.116 + 0.024 0.086 + 0.011 Lead in Milligrams Per Liter of Urine 0.063 + 0.009 0.063 + 0.010 0.065 + 0.007 'lumber of Subjects i 19 15 34 / ( P* I 01478 It would appear that an examination into the relati -nshlp between length of service and lead excretion, mighta means of ascertaining the significance of the lead exposure associated with the occupation of the garage mechanics. This was done first by studying the correlation between the period of continuous em ployment as mechanics and lead excretion, and then by a correspond ing study of the length of exposure In repairing cars which used Ethyl Gasoline, as against lead excretion. The results of these attempted correlations are shown in Table I s . There is a complete lack of correlation in either matter. From these results one must conclude either that the lead exposure associated with the occupa tion is insignificant, or that it of of such irregular occurrence as to have no measurable time relationship. There remains one other means of examining the available data * in search of evidences of lead absorption from the handling of Ethyl Gasoline. Among the subjects studied in 1929, there were twenty-six filling station attendants, and twenty-four tank wagon handlers who had been employed as subjects In 1927. Presumably, if their occupation contains a significant lead hazard-they should show some evidence of change in lead excretion after two years. The findings for the two years, as regards lead excretion, are shown in Tables SC , , and The mean values are summarized in Table It may be seen that no statistically valid difference Is demonstrable TABLE Showing Lack of Correlation Between Duration of Employment of Garage Mechanics and Lead Excretion, and Duration of Exposure to Ethyl Gasoline and Lead Excretion. Factors Correlated Correlation Coefficient Length of Continuous Service as Garage Mechanic with Lead in Faeces in Milligrams per Gram of Ash. +0.017 0.056 Length of Continuous Service as Garage Mechanic with Lead in Urine in Milligrams per Liter +0.023 0.055 Length of Exposure to Ethyl Gasoline as Garage Mechanic '.Vith Lead in Faeces in Milligrams per Gram of Ash +0.223 - 0.099 Length of Exposure to Ethyl Gasoline as Garage Mechanic '.Vith Lead in Urine in Milligrams per Liter -0.243 t a b l e 3$ Distribution of Identic.'. 1 Subjects For the Years 1927 and 1929 According to Milligrams of Lead Fbund in Faeces. Milligrams of Lead per Sample of Faeces 0 - 0.079 0.03 - 0.159 0.16 - 0.239 0.24 - 0.319 0.32 - 0.399 0.40 - 0.479 0.48 - 0.559 0.56 - 0.639 0.64 - 0.719 0.72 - 0.799 0.30 - 0.879 0.88 - 0.959 0.96 - 1.039 1.83 5.10 Total Filling Station Attendants Exposed to Ethyl Gasoline 1927 Number < 1929 Humber 1 53 15 6 30 3 15 2 10 8 40 3 15 JS" 2 10 3 15 1 51 5 1 <r" -0" 1 5 2 10 1 5 1 50 0 sy 0 _.. 0 ! 0 JO 0 0 j> & o; 0 0 er 0 0- 1* 5 0 1* 5 0 0 0 20 100 20 100 Tank "agon Handlers Exposed to Ethyl Gasoline 1927 Number * 1929 Humber P' 0 3 17+ 2 2 4 23+ 3 3 17+ 3 2 12 1 3 17+ 3 j?r -e<' 1 2 12 1 0 0O 90 0 /0 0 0 00 0 00 0 0 '0 0 0 0" 17 100 17 Mean 'robable Error of Mean tandard Deviation J'WAuiii ; a ? 1.1 0^ 0.280 0.030 0.187 *J 0.236 0.023 0.153 0.308 0.025 0.150 01481 0.3US d 0.O2.S ' 0.40JI* 0.036 0.2/S distribution of Identical Subjects for the Years 1927 and 1929 ..ccording to Milligrams of Lead Per Gram Ash in the Faeces aiilifrr-'.n3 of Lead Pilling Station Attendants far "r- it cf Ash Exposed to Ethyl Gasoline 1927 Number 1929 ,V Number : - '.239 2 10 1 5 i - 0.079 5 25 7 35 0 - 0.119 5 25 6 30 o.u - 0.159 3 15 3 15 '.11 - 0.109 1 51 5 O.'O - 0.239 - 0.279 jar |1 e 1 51 5 5 1. 3 - 0.319 ' 0.02 - 0.359 !0 i 6 0.35 - -''.399 0.10 - 0.439 ^ ^ 0 y 1 00 0i 6A 5d Q d d 6 0.44 - 0.479 0 0y 6 0 ( 0.57 6 ib 0 o 0.64 l* 5 6 0 1.36 Total l* 5 o 0 20 ~ "loo 20 100 Tank v,Qg0n Hancilers Exposed to Eth? Gasoline 1927 Number 1929 if Number if 1 6 7 41 4 23+ 2 12 5 30 3 4 23+ 2 17 12 3 17 1 6 0 01 6 0 0 <P i 0 60 0 0d 0 0 i O' 0 00 0 0 00 0 0 00 b 00 6 0 00 0 0 00 0 17 100 17 i 100 Mean Probable Error of ean 0.11S 1 0.015 0.106 t 0.009 Standard Deviation 0.093 0.058 ^Excluded in calculation of mean . .- p .t .4 i Id ^ hi1* >***`L*-.G ' 0.109 io.ooe 0.047 O. I (^ 0.0(0 0.142 ^ io.019 0.117 t a b l e : ll Distribution of Identical Subjects for the Years 1927 and 1929 According to Milligrams of Lead Per Liter of Urine 'illlgrams of Lead Per Liter of Urine 0 - 0.039 0.04 - 0.079 0.08 - 0.119 0.12 - 0.159 0.16 - 0.199 0.20 - 0.239 0.24 - 0.279 0.28 - 0.319 - 0.32 - 0.359 0.36 - 0.399 0.40 - 0.439 0.58 0.87 1 1.00 4.00 - + Total Pilling Station Attendants Exposed to Ethyl Gasoline 1927 1929 Number if- > Number gf 3 11 7 27- 9 35 7 6 23 9 35 3 11 0 0 1 41 4 2 81 4 0 00 0 1 0 00 0 0 00 6 0 Q0 0 0 d6 0 1 40 6 1 40 0 2 14 JST JO -e-- .0- 26 100 26 100 t-i Cvi Tank wagon Handlers Exposed to Ethyl Gasoline 1927 Number XT' if 1929 Number 6 i 25 /> & su 11 46 2 8+ l H+ 1 4+ i 1 4+ 0 0 J2T fis 0 0 1 4+ Q 0 jar l 4+ 1 4+ l 4+ ,0 jyf 1 ,0 -er fir .0 or 0l 4+ JO" 2* 24 0 0" i 8+ j D ' -G" '2- j1---0---0-------------1-----2--4-- ---- 100 Mean robable Error of ean 0.142 . 0.024 0.111 0.025 0.129 0.015 0.115 # * 0.024 tandard Deviation 0.180 0.188 0.106 - 0.173 * Excluded in calculation of mean #* Mean drops to 0.083 + 0.11 when one result of 0.87 milligrams is excluded. 01453 t abl e: 3 $ Summary of Mean Values of Lead Pound in Samples of Faeces, of Lead in Milligrams per Gram of Ash in faeces, and of "Lead in Milligrams Per Liter of Urine for Identical Subjects Examined in 1927 and 1929. ;-=>ad in Milligrams in ingle Sample of Faeces Filling Station Attendants Exposed to Ethyl Gasoline Tank Y.'agon Combined Handlers Filling Station Attends: Exposed to and Ethyl Gasoline Tank Wagon Handlers 1927 1929 1927 1929 1927 1929 0.280 0.236 + 0.030 +0.023 0.308 0.402 +0.025 +0.036 0.294 +0.019 k 0.312 +0.022 iSad in Milligrams Per ram Ash in Faeces 0.118 0.106 o.m.5 +0.009 0,109 0.142 +0.008 +0.019 0.114 +0.008 0.124 0.011 ,ad in Milligrams Per .iter of Urine umber of Subjects 0.142 0.111 0.024 0.025 26 26 0.129 0.115 +0.015 0.024 24 24 0.136 0.015 50 0.113 0.017 50 / f 01464 Chapter VII Certain Considerations in the Prevention* Diagnosis and Treatment of Lead Poisoning 1. The Prevention of Lead Poisoning Among the General Population. The necessity for further detailed knowledge of the opportun ities for lead absorption under present conditions, and the anticipa tion of new opportunities arising from changes in the life and activ ities of the community. At present the largest factors which differentiate the modern community from primitive life are found in candies and fruits. The spraying of fruits and leafy green materials with lead arsenate is the largest of these factors. Necessity for particular caution in the lead contacts of young children (cite literature) because of their apparent suscepti bility* their unusual behavior - pica and their natural tendency to haye hands and other objects in their mouths - and the disproportion ate frequency of encephalitis. Inexperienced and ignorant manufacturers of beds, toys, etc. coated with lead paint. Repainting by parents or others. Drinking water, lead nipple shields, lead-contain ing cosmetics on Mother's skin. Other items of importance. Typical case records i Lead Poisoning in Industry. The recognition of exposure to lead compounds - air sampling methods versus studies of lead excretion. (See typed article on this subject.) The limitation of exposure - means to be suited to occasion. Sharp segregation coupled with measurements of exposure as influenced by improved methods of eliminating danger. Not adequate until lead poisoning is completely eliminated. This means exposure must not be sufficient to injure even susceptible persons. Careful medical supervision will usually serve to prevent tragedies while the methods are being perfected: Rejection of diseased persons in lead trades, "Symptoms and signs of impending intoxication. Stippling and other blood changes* What are safe limits of industrial lead exposure in terms of the methods of measuring exposure? For practical purposes the exposure must be reduced at least to the point where the lead ex cretion of representative group/*" of workers is within the limits which are not associated with the occurrence of lead poisoning. It should be limited to such even lower levels as are compatible with the application of reasonable methods of control. If this can not be done except at an expense which brings economic ruin to a lead industry, it would seem that society could better endure the loss of the industry than to pay the price exacted by its continua# tion, 3, The Diagnosis of Lead Poisoning. ^. Three points: 1. History of exposure, 2, Characteristic/ symptoms and signs, 3, Establishment of significance of exposure - knowledge of conditions and their relation to cases of lead poisoning. Chemical analysis in appraisal of exposure. Difficulties in case of sequelae - malingering, vague sub jective symptoms7r"non-specificity of symptoms or signs or sequelae. There is no laboratory short-cut to a diagnosis. The only thing the laboratory can do at present is to establish the signifi cance of the exposure* Studies of faecal excretion within twenty-four hours of cessation of exposure give magnitude of exposure in dusty trades. Studies of urinary excretion of more value under the usual conditions because of the persistence of abnormal findings, uncom plicated to a large extent, by dietary lead. /'.'--If 1- p O a' et- I J- - The laboratory signs of lead intoxication - valuable but not specific or final. Lead in excreta, lead m blood, blood changes. -- --------------- ---- Typical cases: Observations following immediately after ex- posure. Delayed observations. x, J?' The curve of lead elimination in urine - Smith, Foster, Jones. The slope of the curve in relation to severity of exposure. With knowledge of the time interval since exposure, and with two or more points established the curve in any instance can be projected to give a measure of the relative magnitude of the exposure. Fatal cases without observations prior to death. ^ Post mortem analyses and their signiiicance. Uuncentration of lead in certain tissues as liver and blood. Gross amount of lead as indicative of significant exposure. The time of exposure may be determined with some degree of accuracy ir^m me quantity of lead present. The extent of the exposure can be determined if the tjyme factor (since exposure) is known. The accumulation of information as to the amounts of lead present in human tissues in relation to determined rates of lead excretion may eventually facilitate the formation of accurate estimates in terms of actual amounts of lead in the body, 'If this be accomplishec analytical methods alone will serve to answer some of the Questions which present themselves at the necropsy table-,' The amounts of lead in the tissues of an individual who has died under conditions which permit suspicion of the existence of significant lead exposure will then establish the facts, in relation to the time interval between cessation of exposure and death. Typical cases: (l) normal amounts of lead. (2) abnormal amounts of lead. Lead in the brain and its significance. Typical cases: no exposure! significant exposure. 4. The Treatment of Lead Poisoning* Removal from exposure. Normal elimination of lead versus induced elimination. (l) Unnecessary. (2) Dangerous, especially in children and severely exposed. (3) Unavailing because of brevity even if doubtful accuracy of observations be ignored, and because of the brevity of periods of treatment. Such brevity enforced by reason of economic necessity. Hospitalization and medical care are costly and are not provided for by compensation courts. Rest, freedom from anxiety including economic. Full diet, profuse liquids, alimentary tract kept freely eliminating. MgSO^., etc. \ f r> 5. Compensation Cases of Lead Poisoning. Proof of exposure in relation to occupation. Duration of disability. Re-empioyment t 6. Theoretical Considerations. In view of the conservatism of the conclusions which have hitherto been drawn from the data^ which have been presented the writer 's may be permitted to indulge in a few speculations as to the meaning of certain matters which have had only a partial or practical inter pretation. Perhaps such efforts may bring into relief some of the problems which require solution. See The factors which are active in the production of lead poison type written ing are but poorly understood. Why is it that one individual may be article on sub- exposed to a certain set of conditions for years without apparent ject. injury, while another becomes ill after a short period of exposure? Or why does one and the same individual persist in good health for a long time only to develop an unanticipated acute attack of colic or neuritis or encephalitis. One may suspect that in many instances these results have arisen because of the presence of diseased persons in lead trades# or because the signs of impending intoxication were not sought for. Certainly the term "unusual susceptibility", has been a most convenient term under which to conceal faulty observations, and by means of which to sidestep the responsibility for the maintenance -of unnecessarily hazardous conditions in lead trades. Nevertheless, variability in susceptibility is a fact which must be dealt with in the interpretation of the nature of lead poisoning. Does lead accumulate in the tissues of some individuals to a greater extent than in others, and does this occur more readily under cettain physiological <x> nditions than under others in the same person? If so there must be a certain variability in the chemical compounds of lead in the body under a variety of conditions. The nature of these compounds and their reac tivity under various conditions, must be known before we can hope to understand the mechanisms of lead absorption and lead intoxication. /' Some clue to the existence of important chemical compounds in the body may be found in the relationship which apparently exists between the rate of lead absorption and the rate of urinary lead excre tion. (Piet accurate curve of faecal lead content (exposure) versus urinary lead concentration, showing the point at which a critical break occurs.) At a certain point in the absorption, elimination fails to keep pace, showing little or no proportional relationship to absorp tion. At this point the excretory ability of the kidneys reaches a maximum or else some chemical reaction has reached its limit, thus permitting the lead to be distributed into the tissues. Something definitely modifies the release of lead from the body. This point is probably the beginning of rapid accumulation of lead, and if it can be established definitely in relation to exposure it should be easily possible to distinguish between a safe level of lead exposure, and Hl l . that is not safe. At this point any individual is in danger of being poisoned. Presumably susceptible persons reach this point in advance of normal individuals, as an expression of the existence of chemical factors which promote accumulation, or conversely, as a consequence of the absence of chemical factors which promote elimination. That this is not always a matter of disease, but may occur within the limit of normal physiological states is demonstrated by the susceptibility of infants and children. ) Experimental ?'ethods , I In a field as many-sided and as replete with possfl- ! /\ /' jbilities of error as the one under discussion, it is pbvtous I '/ I 1the validity of /esults\ or conclusions depends/pri- j marily upon the accuracy and adequacy of methods of procedure. In fact, one of the obstacles to a proper of much of the * i* work on lead compounds arises from the fact .that methods are'not described with sufficient de finiteness to justify judgments as to their accuracy or to permit of their duplication. Therefore at the ,ri.sk 0f intro ducing Intrinsically tedious material, 1-fr boeemoo eooooP"&iy -to- set dovm- dotalls -ef experimental methodsep*SJ 7jLe$-cu$ is *. -f r->. U-^ '/ 1. Analytical Methods (1) Analysis of Urine. Samples of urine are collected in gallon jugs of the type used for fruit juices. The volume is measured and for every liter of urine 100 c.c. TE.r03 (Sp.Gr. 1.12) and 10 c.c. TTs S04 are added, unXU care when dealing with ammoniacal samples. (:TaS04 is used to avoid excessive alkalinity .of the ash.) The sample is evaporated to dryness on a hot plate at approximately 105 C., is trans ferred to a 500 c.c. fyrex dish and again evaporated to dryness at 105 C. After ashing in electrical muffle furnace at a \or temperature controlled by pyrometer so as to exceed 01 491 500 C., the material is cooled, moistened earoPtrl-hy with dis tilled water, and treated with 20 c.c. :-:M0a (1:1), the ash being broken up with a stirring rod. Distilled water is added to bring the volume to 50 c.c. and, following digestion on a hot plate, the residue is filtered off and discarded after re peated washing, alternately,hot HN03 (1:1) and hot v/ater, the filtrate and washings being caught in a 600 c.c. Pyrex beaker. The filtrate ^ia evaporate*! to dryness on a hot plate at 105 C.' ~The residue is dissolved in HCl (1:1), is diluted to 300 c.c. and is neutralized by adding 25? PaOH until just 0.1% alkaline, 4 drops of - aqueous methyl orange serving as indicator. HCl (1:2) is added to the faintest pink, the solution is cooled, and gassed with HeS for one hour. After standing overnight the precipitate is filtered off on.a 12.5 cm. V/hatman //40 filter paper and Is washed thoroidghly^with freshly prepared HaS water to which has been added 0.1;' of its volume of HCl. The precipitate is washed off the paper into t the beaker in which it was produced^by means of hot H!T0o (1:1), followed by hot water, the sides of the beaker and the gassing tube being sladLiUrly washed. The solution is evaporated to zjhr. small volume^transferred to a 100 c.c. Pyrex beaker, treated "ith 1 c.c. HsS04 (Sp.C-r. 1.G4) and evaporated -to fumes of fV. < paper with a solution containing 1 c.c. HsS04 (3p.Gr. 1.84) to 10 c.c. 95;' ethyl alcohol and 20 c.c. water. It is then dissolved off the paper into a 600 c.c. Pyrex beaker with ._____________ JHSHBn hot ammonium acetate, followed by hot water. (This is SSBt done by first washing the'fbeaker in which the S'* ackTcLfe, precipitate was made, then decanting the solution and wash- &-*.y jc.c. q_ ings througn me filter.) This solution, now diluted to"'^<- ^i.c ^ , _o . 300 c.c. with cold water, is treated with 2 drops HN0a 5 , y `a7^e-- V -Ob*. c-ca (Sp.Gr. 1.42), and is neutralized by adding 25?( NaGit to , kf. alkalinity, then HC1 (1:2) to a faint pink to Methyl Ked ' tc cy (4 drops of a 0.1'( solution of Methyl ked In 50;' ethyl alco-/? ` - hoi). 1 c.c. KC1 (1:2) is added in excess, the solution is cooled, gassed for one hour with HeS and allowed to stand **- overnight. The precipitate is filtered off, washed and re- Sc- ' ** `4 , dissolved Xif ( the) same methodsT^ricfprecautions as employed ? , at the previo1us su/ lphide step. The solution is evaporated ^ !-'rj t ( ''Uv to 1 or 2 c.c., and transferred to a 150 c.c. Pyrex beaker, J'"Vr '^ where it is diluted to 80 c.c. with cold water, neutralized ^ with 25' NaOK (free from iron and aluminium), ; 4 drops of a solution e#n0.5^ phenolphthalein in V" aqueous NaOH, as indicator. 5 drops of 25J' MaOK are added in excess, for the purpose of supplying enough sodium acetate to repress the F+ ion concentration due to the presence of small amounts of mineral acids, when the solution is neutralized with 5f acetic acid. After adding 2 c.c. of 5)' acetic acid in excess of that required for neutralization, the solution is brought to a boil and treated withc.c. of If KaCr0* solution, the mixture standing on a hot plate for one hour, and at not 0'1 4 9 3 less than 60C. overnight. The precipitate Is collected on a 7 cm. Hunktell #1-F paper, the beaker and paper being washed thorough&pj**' with hot water to remove the last traces of soluble chromate (tested with diphenyl carbazide till washings do not give a pink coloration), and is then dis- solved into a 250 c.c. Mohr flask containing 100 c.c. water, 5 -- j 30 c.c. cold HC1 (1:5) followed immediately by cold i Zj v/ater. The beaker and stirring rod are washed and^decanted through the paper. In a similar flask a standard is prepared containing sufficient KeCr80y solution to be equivalent to 0.30 mgs. lead, precipitated as PbCr04. 100 c.c. water and 5o 20 c.c. cold HC1 (l:iT) are added. To the sample and to the standard, 2 c.c. of a if. solution of S-diphenyl carbazide in glacial acetic acid are added. After the dilution of each to 250 c.c. and after thorough mixing, the estimation of lead in the sample is accomplished by comparing the intensity of the pink color with that of the standard, a Duboscq colorl- meter. f ^ l'C.C , Si XU. A.'. .X. t. 0 c_<t t - v <fi~ : ' . J. a . S~C.-< _ f- ,S"s> ' ' -T/'' -7" -C-i- V. ' i. -- ' -f (2) Analysis of Faeces -- v_ /? ' 'T_-Cc < .-i* s/ - {} "C-+" 4 ' y Samples of faeces are collected in glass-capped quart or pint preserve jars. Each sample Is transferred to a 500 c.c. weighed silica dish, dried to constant weight on a hot plate at 105 C., and then ashed in the same dish in an 88 014 9' electrical muffle furnace at a temperature controlled by pyro meter so as not to exceed 500 C. After cooling and weighing the ash, distilled water is added wit% eabe and the moistened^ i O'/'i, ,u*,+ rCr iZa.t-aL I err. H^ c.. e. , - ~~ - v-A < c /'./*--I e-e- -)^C 'i/A-fu A- i` t1.'X Ou.< c'f S-O ash is treated with 20 c.c. HN03 (1:1) while being broken up with a stirring rod. Hot water is added to bring the volume to 50 c.c. A period of digestion on a hot plate is follow ed by filtration into a 600 c.c. beaker, the residue being thoroughly washed alternately with hot ffiI0o (1:1) and hot water, and discarded. The combined filtrate and washings k. '<U> J^LlCCbi Co-icL. 7-Sc. <Z . <2^ are evaporated to dryness on a hot plate* ^he residue is cx^d dissolved in F.Cl (1:1), is diluted to approximately 300 c.c. tact! <V >, \ in a 600 c.c. beaker, and is neutralized with 25^ NaOH, added drop by drop with constant stirring until a slight permanent turbidity is present. The solution should be cool, and should not be permitted to become appreciably warm while being neu tralized. A few drops of 0.5^ aqueous solution of methyl orange are added, and if the solution is alkaline HCl (1;2) * is added to a faint pink. Following treatment with II3S for one hour the precipitate is allowed to settle oversight and is / filtered on a 12.5 cm. Whatman #40 filter paper and is washed with freshly prepared K8S water to which has been added 0.1.'' 's of its volume of TIC1. It is then re-dissolved Into the beaker - in which the sulphide precipitation was made, by means of hot HCl (1:1), to which has been added 10 drops of concentrated H?IOa, in order to dissolve any CuS and thereby prevent occlu sion of lead. The s'des of the beaker and the gassing tube are washed down with the acid, and the paper is further washed well with hot water. The solution is permitted to digest until all the H2S has been driven off / whereupon it 13 diluted with cold water to 300 c.c. From this point on, the second neutrali zation with NaOH, the second precipitation with HaS, and the 01 495 subsequent; steps of the analysis proceed exactly as in the case of the urinary sample. (3) Analysis of Food, Tissues and Other Materials. These materials are collected in glass-capped quart amounts of cal- cium or fat, the general procedure, after weighing, is to in troduce suitable quantities into 600 c.c. Pyrex beakers to gether with 10 to 20 c.c. concentrated HNOs, V c.c. concentrated HCl, and 5 to 10 c.c. concentrated HaS04, taking down to a char on a hot plate. The char is destroyed by freouent additions of small amounts of concentrated ITN08. Near the end of the pro cess 2 c.c. 60^ perchloric acid are added, while additional amounts oi* KN03 are introduced until no char appears on evapora tion to l!3S04 fumes. The material is evaporated to small volume. cooled, and treated with 10 c.c. concentrated PCI and 350 to 400 c.c. water. The regular analysis is carried on from this point. lio HaS04 is used in the digestion of bone or of tissues which cousin bone. Such materials are treated, with suffi cient HiIOa (Ii3) to complete digestion, after which the sample 13 evaporated to dryness on a hot plate at approximately 110 G. The residue-is taken up in 50 c.c. concentrated i;NOa and hot water, transferred to a silica dish, again evaporated to dryness, and ignited to a white ash in the electric muffle furnace at a temperature not higher than 500 C. The ash i3 moistened care fully with water, is treated with 50 c.c. concentrated HNO-j, iSc B 01 496 and set on a hot plate until dissolved. The residue is fil tered off and washed alternately with hot T!N03 (1:1) and hot water. The filtrate is evaporated to dryness. The residue is djtoaol1red in concentrated HCl, is again subjected to evap oration to dryness and is finally taken up in a minimal quan- O'1' tity of crer[pS^ntT^iaad HCl. Upon being diluted with water to approximately 300 c.c., the usual analysis is carried out. Fatty materials are dealt with "'IU| *-n by heating with concentrated UsS0* to an incipient char, after which they are treated with successive small portions of concentrated HN08 until no further char is present. The sulphuric acid solution is evaporated to small volume, whereupon the slight char which appears is destroyed with small amounts of concentrated RN08 and 60*( perchloric acid. This entire procedure is accomplished with on* speed and convenience if the sample is divided into small quantities in Kjeldahl flasks. Constant attention is required. U,Remarks on Analytical Methods. A survey of analytical methods In si/ 1S24, resulted in our use of those developed by Fairhali , with certain modifications instituted by " nr.-'a, Edgar. Fur ther efforts to shorten the method and to reduce the slight losses of lead to the minimum, Jiaw resulted in investigation of technical procedures originating in the minds of the lab oratory staff, or suggested by the work of Avery, Hemingway, 5/ '4/ Anderson and Read , Taylor , Francis'7 and his associates, and Tannahiir" . The preparation of 9B samples for analysis by Uj-O^ primary ashing at low temperatures (500 C.), ha e-bo on aban doned in favor of initial wet digestion methods except in the case of faecal samples. Furthermore has seemed safer not to place too great dependence upon the quantitative separa x/ tion of lead from urine by treatment with ammonia as suggested, with certain qualifications, by Fairhall , or by precipitation with the oxalates as recommended by TaylorA- s, though we have not investigated the latter method. The sulphate step, after , the manner of Avery at nl., has been found 18 MU inmaa necessary "to the Inclusion of materials other than lead. The colorimetric determination in which chromate ion * is measured by means of S-diphenyl carbazide has been so satis factory in our hands that tfe havk been loathe to eliminate it in favor of a thiosulphate titration, sulphide precipitation, or the acid sulphite methpd of Ivanov . The thiosulphate titration method r-;\ A 5ud.gffi.an t, in S' \ 1 I-n- -gwi.with amounts as low as a few hundredths of a rallllgram--.in The the carbazide reaction SpBRS3 L. . J,. J, upon chromate ( instead of lead becomes of aAne a * significance cw:.le- :.4 */ ,04 \J> J .vhen that the qspSA elimination of soluble chromate may, be .. l'it / ' v ^ t-j. ` ^ t ^ 6*^ t4agsaas$ . m.i-u.-l la..' .i 1 by the? care^required to- ovoid the inclusion of non-lead materi als in /the other two colorimetric reactions. An advantage in the use of S*diphe;nyl carbazide is found in the identical Quality O'f the colors produced In the standard and the sample* a_mBJkter~ raTST^'a-cc comparisons*' *$ It would be highly desirable to dispense with the numerous steps of a purely chemical method, which involve slight but inevitable losses of lead. Nevertheless the re sults of our investigations derive their significance from the certainty that the methods have not yielded errors on the high side. Thus while slight uniform losses of lead are to be de**>* olored, they do not Influence the validity of results, wMrch oftuld na.t..ha,v6L-her-n-obtained with--lose- aen-sltiye- gethfdaj on J t.trn .nnA hand r nnf ^ th. -moTta--.3ra. > +- .1 a??--i^n-3-f mrl y h\J j-- ------accurate pnooe-dHJ^es. on ' the- utttei*. . furth^irmar-a, pfrrfnln defi- nite advantages have accrued from the accumulation of comparable data over a period of years. Tha^gradual modification, pf nathods on_the--baai s oilgag3P asc&ntjriTreTTT'act^ e maintainingchnical-uniformity-'irfhrrvrl nr i ban -rfnTilorTT' body of. increasingly conclusive 1 nforraaiioa, -?*a tei'TaTs" and Technique m, 014 9 9 W Satisfactory results from the employment of' any method of analysis for lead are predicated on the utmost care against the Introduction of lead from containers, reagents, and experi mental procedures. The opportunities for contamination In the laboratory are slight*J&ggfiktta*, as compared to those associated with the co3J.ection of samples %ef anyIt_ is_jiecoasary to i t\ Ai-A,!/ ***- /L+t+X .. J*l*i*. ,J ' v ri^jL^ttcij L-niXuAii} "L , i ul,..i. "T * U c*st rj -j^l. -- < K A, oM.'s>- UwrfL-. (rnJ bvctjfr'if /-,y -___ it \u.u\ .. a . . o 'I h?**.L* aI+S** supply chemically clean containers of glass which will not yield appreciable quantities of lead to the sample regard less of any chemical changes which may occur. It is mmt%- essential to eaee that materials are collected into these containers, without the use of any intermediate vessel, and with adequate precautions against foreign materials which may be present in the air or upon the hands or clothing of subjects Continual attention to these details is required to avoid gross contamination. Where intermediate containers are unavoidable as in case of persons confined to bed, special equipment is required which must be handled with laboratory technique. V ' -*/ .t\ .V i'W The lapgoe'%--poytlen of our samples have been collected in glass capped preserve jars, and in gallon jugs with cork stoppers. These have been cleaned in the laboratory with the same carq as that employed in the case of the other glassware, fhe ) technique here is of some consequence. Tap. water as well as cleaning reagents may contain appreciable quantities of lead. Special care is needed to assure lead-free distilled water. Thus the tap water and the distilled water are analyzed from time to time to assure their satisfactory quality, while the best quality of Sulphuric Acid and Sodium Cichronate is used as the cleaning solution, in order to avoid the contamination of lead found ' frequently nnri"* durrh? t - ir nI Milrr in the commercial vani of . The possibilities of contamination from the glass containers, have been tested by treating certain ones selected at random, with half their volume of hot nitric acid * allowing them to stand on a hot plate at 105 C. for two days, after which the acid and washings were analyzed for lead. The highest results obtained have been 0.01 milligrams of lead, in the case of certain quart preserve jars. The gallon jugs have yielded no measurable quantity of lead under this treatment. To determine the maxim/ possibility of contamination certain of the containers have been broken, one-gram samples were de composed with chemically pure sulphuric and hydrofluoric acids, and after fuming the residue to remove hydrofluoric acid analysfes for lead w h s carried out. i.'ason jars are somewhat variable in their lead content, results varying from nil to 0.2 milligrams of lead per gram. The gallon jugs contain uni formly negligible amounts. Corks used to stopper the bottles, and rubber rings used to seal the jars have been analyzed., A typical determlna- / tion showed 0.07 milligrams of lead in 5.45 grams of rubber ring, while 6.6 grams of, cork yielded no lead. The glassware used in the analytical procedures con tains measurable quantities of lead when decomposed with hydro fluoric acid and analyzed. However, the ,amount of glass actu ally dissolved is quite small, and in no way influences the results, as shown by blank determlnations. Lead-free reagents may be purchased, but considerable care must be taken to test them in this regard. Having estab lished a source of satisfactory supply, a uniform purity is reasonably MH assured, but it is desirable to keep a continual check on the matter by making regular blank determinations. We / have made a practice of running not less than two such control determinations with every set of analyses, thereby aecurIrvg 1,-z* ourselves -e-P the amounts of lead which nay be contained in the maxinai amounts of all the reagents employed in a single analy sis, "hile at the same time testing the uniformity of the analy tical procedures In the hands of the laboratory staff. Over a period of many months 96,- of all such blanks have failed to show traces of lead. In no case has the quantity exceeded 0.02 milli grams of lead. By means of scrupulous care in carrying out the technique of the analytical work, and by maintenance of the utmost cleanli ness of the analytical laboratory, as well as > continual check on materials, equipment and technique, it has been possi- ble to u j . Mi"*"'h'ir gagfiacaaaBSSBs against high results. Slight loss Of lead is haomioa nP frKa .^c l ^.1 ^ fry.....,.q.-.a n mp n vital ch usually Tn^ 'liiiVI-g The results, there fore, err on the low side. The extent of such errors is indicated by' a typical experiment designed to test- the analytical procedures only, i.e. in the absence of organic materials. Lead-free control samples containing 2.5 grams CaClf, , 4 grams ;iaa?0^.12TIg<j, 10 c.c. EC1 (Sp. Or. 1.19) in about 300 c.c. distilled water^ were treated with variable quantities of lead unknown to the analytical 3taff. ' The results ire shown in Table I -i , .. ` Table I r> i* t- '/_ . V...., , ' s ` ' i " Milligrams Lead Added Milligrams Lead Found Mil Nil Nil Nil 0.07 0.07 0.07 0.07 Mil Nil Nil Nil 0.05 0.04 0.04 0.04 Milligrams Lead Added Milligrams Lead Found 0.20 0.20 0.20 0.20 0.25 0.25 0.25 0.25 0.14 0.14 0.12 0.15. 0.18 0.18 ) 0.16 / 0.19 r r\ ~7 O Kj 0 3. *'ethods of Estimating Basophilic Stippling of the Erythrocytes. The changes character. q=:frfre erythroc,^ tgs~ uf - the blood-; in .rotation to |U / ft; c* .* _ f* r- the absorption of lead compounds, gtmaaf a specific impor- tance to micVroscopic examinatlon/s/of the blood in cllni-A^ ' - cal or experimental work which /Concerns Itself with lead. / ^ Without preconception as to the relative merit of the methodise > / * K fr of detecting variation i.rn//the content or distribution of | ^ %^ y ] basophilic material in r,^d blood corpuscles, we have elected to make observations \ *. jjv the\occurrence of stippling in blood . p ,x smears unmodified by fixations haemolysis or by vital stains.> - The adoption of this as a general procedure on all cases, > *: even where in .srorae instances additional methods were em- / )loyed, was based/on the impossibility of sampling by any /\ other mean's than that of a dried smear, under certain condi- -",-f i tions of our work. Thus we have attempted to obtain a satis^r & ,- < KZ ' , _ i factory degree of quantitative accuracy in a simple method r=5afc>Er!ih^* ^* (v .applicable to any subject at any distance from laboratory facilities. '* ^ j ct _ Several imear3 are made from the blood of each sub-5-? i n '''it eftt "? 0 a*\) "ti . cnr 'ml f ^rm nMrwtr" "nd--^*^nnngr nr *P ' , a P ttT,7rt't1rnftyt:fta nr }^ea<h1flr.nn r h an ^ pl ait y-Alftiirt The slides are perm.-1 ted to dry naturally. A**y are 'x ^ *> * ^ labeled with the subject's name or number and the date^ They \' ^ f J may be e.xaa&nod--fafi" the-'laberntony nt. once nr wten weeks later|S^ u> c^ioJS x(^ c.*j____s, (-u jp) f' ^ f ' I 01 5 04 . rr-vyr^j "jr '-wu.......... ' ^ lij-Qn^ rlnon. y At-^bj4A4rf*s"-^hy aro inspe/tec^^ancT^d'ie^ best and roost uniform i one3 are selected for staining. The stain employed is made up '"T of 1*5 grams /ethylene ^lue, 0.2 c.c. of l'' tfaOH in /ethyl /lcohol, in 100 c.c. Methyl Alcohol. The smears are immersed in the stain for four seconds, washed rapidly with 0.025;' aqueous TlaHCOg solution, and dried 'ey u rapidly ju&fiMin a strong air current. The resultant stain is brilliant, and the stippled erythrocytes are easily recognized. The erythrocytes are stained a pale green, while the basophilic granules are a very dark blue. The criterion of the satisfactory quality of the stain is the relation existing between the pale . reen translu cent appearance of the erythrocytes and the depth of the nuclear staining of the polymorphonuclear leucocytes. X nr*' ybfc til p (Experience, careful technique and micro scope lenses capable of excellent definition are required to obtain good results. 54--lo deolrable-^fr1 wtamintT'^i^he smears in a strong light, ^.vith a magnification of noteless than 900 diameters. -gWfrff/f1 j luh uuy exUaia^d, /y . eryThrocyte in -rhe "fie^Ld. -In -aur-ceere nm* intf7n f' f1r*r "i"~t Tr^frr t4rn ` hnn ffc *~hn or> of the central portions of a great many more fields. &i.-- U4JJ tMt4******r^i in observations in which .the npp nf prn "pi *- ~riL~ .employed,. Ccaefvri selection of fields of most nearly uniform distribution of erythrocytes reduces the variation in the jj^g 01 505 number per field. hovor feliel'ess considerable. t s ?ietion in--thi.'s*" far Lor -aftfiura The number ^per field averages approximately 250. In i h s iIpj t nf nhasryafrions. 3mmr& fifty fields imately 12,500 erythrocytes. b mb HiI i..i i approx ^ ^_ 7>**c appreciation-of the limits of quantitative accuracy v obtainable, in view of -9ttt the opportunities for variation in tech nique m the hands of a single careful worxer, may oe had irom a con sideration of the observations of Table II. Ten successive smears of the blood of each of three subjects were made, after which the microscopic examinations were carrieu out by one person. ^ Variati ons in the results obtained by two persons are shown in Table III. Each observer made ten successive counts on a single smear, thereby showing the limits of variation in the technique of microscopic examination. Then each observer made one smear from successive drops of the blood of the same subject and agairumade ten / counts on the smear so prepared. The c/unparyson of these two sets of results gAvaa sum ft. id-aa--of the variability which may arise from the preparation of smears, plus the microscopic technique.--^ I-t may be seemn tchnaa t thei e io o fair Jegrch'""5T"'aecursrgy in" Tn fao-fe,<ffi-rgnnn 1rtmrt"1 lassaos2-",|-iphhee data wiiich 8pL appear ; in subsequent pages show^ that the accuracy of observation is greater than the accuracy ai interpretation in relation tc the question at issue. 4. General Clinical Metnous 01 ^06 " ' v" ^ nf1 mnr nlafzy' + excellence of clinical observa tions is dependent upon the skill, care, and judgment of the observer ./ rather than upon specific methods.. Thu a.,--It. is pi-rfitrrMr to da^pi o p . ii -la of, iwfftrt-innn i iit. the eantial, pnrpaae.a. urtLj^ Wtt, <C*j[ Table II ..t , . 7 y' .-.U-t-tt '. / , . ./ . ,, /. x tiLl Observations on Ten Successive Smears made frog Same Subjects Smear 1 2 3 4 5 6 7 8 / 10 Average YU<~*Uj trj Sj.jUj3 Subject B. Subject J. Subject N.S. 5 19 141 11 26 145 9 17 180 7 26 135 11 19 163 7 22 165 9 24 138 14 21 169 7 31 150 5 13 131 8.5 21.8 151 i V 01507 Table 2L ' jvrif,J 'Jit -I-:. ?. t'W&a-uS 'Xi/ilS <1 ~.1 2 3 4 5 6 7 8 * 10 ^ SkU^X^x ^, /^JU ^ rf. A/ X<*<^4w, <L*j c#^vu-J& '*/ . tvs si ') f.lS.J,? U~j "fZm (f**0**, t*lsf' *-j UrlUn-J 1*4 Af,CtM tfcc <wi-. J # - r > .* cBeeryStloji^on `Ptfoj Smears ^ qa fSfngi* Saw, /,< L/ fi^QjjrSame^Sub.lWe^ --------- vV by D. / by S. b'niAviUi* by D. { *iiuvr*$ <* /`V'i i by S. 1 2 3 4 5' 6 7 8 ;) 10 Average 28 38 31 37 40 34 29 39 38 32 35.6 30 36 36 32 38 33 34 35 35 38 34.7 1 2 3 4 5 6 7 8 9 10 135 110 141 119 117 118 115 117 113 113 119.8 89 91 110 101 /" 97 7 106 92 85 110 106 98.7 vf ^ 7. yM ..vOCMLAUtt**cSLr~d Am^Ll k c ,J $ Aaltjfc. if**%, |oe atlonlng of every subject was required, in order, to .etermine the occurrence, duration and signifi<.^3 cance of^exposure to lead compounds* So many trades involve some contact with lead that arej\il 3,cruLluiy-u<f the entire C ***+dtr<*-P * ~"s occupational history anal >>" ** i-juliiu thlo mattor. UAAti %~Ho GV<ak & W&h*jTur4*J& '^**-14**1* aura tn,lj^a<i..qflninn3il.nTi^i. & was desiruoie to individuals who exhibited evidences of chronic or acute disease which might interfere with normal absorption, metabolism and excretion. 3. |C <Lfvrv..J U*JUJ v in | 1 effort wao--aado to detect) -e^idenres nf .lllfteea of..inny-iaind,^ <**X -attention was given to the discovery of abnormalities associated with lead intoxication. 7 4- Jo t ttje sake of of various groups of subjects, information 'oofi a quantitative yd'hafacte^, / // /S was obtained 30 far as ^oss^ble* /\ tleerl raSTgSfr dala.*_and of -*44. other,,mmaaft^j^te?i s,,ame.nable -to-matheme-te-ical- treat- mnnt) ^""n '">Hd ni 111* ! 'v--n-'-r-gtrl nv-frogeduro , -4 a*J i-s-vw-ir V Jt. rtcLJ 7iQ - \, l *>V\ * > L$& . ^ itwi. ,,>-0 -S*'-< & <<. tr -1+*.^+,.- .iJ \ 1/ Bibliography t . y y. vFairhall, L. ?.: Load Studies. I, The Estimation of Minute Amounts of Lead in biological Material, J. Ind. Hyg. 4: 9, (1922) ~ 2y vAvery, D., Hemingway, A. J., Anderson, V. G., and Head, T. A.: Determination of Minute Amounts of Lead in Water, with Uotes on Certain Causes of Error, Proc. Australian Inst. Mining and Metallurgy,43, (1921). 3 Cylyli:0^ '^Taylor, H. B.j The Determination of Minute Quantities of y Metals In Biological Material. Part 1., J. Proc. Roy. Soc. New South V/ales, 61.: 315, (1927). V ''Francis, A. G.., Harvey, C. 0., and Buchan, J. L.: The Determination of Small Quantities of Lead, with Special^ _ Heforence to Urine and Biological ?.laterials; Analyst, iT 77 2-6 December, 1929. 5, , Tannahill, R. V.: A Critical Survey of the Methods for the a. Determination* of Lead In Biological Material. Med. Jour. ' Australia 1: 194, (1929). y .TFairhall, L. T.;. Lead Studies XI. A Rapid Method of Analyz ing Urine for Lead: J.Blol. Chom. 60: 485 (1924). 7/ l C'U ivanov, V. N.: A senBl-4-ive Reaction^ Lead. Chem. Zeit. 38: 01 u 1 l