Document jgYQ8vX5jO5aj9MDNB7k4qyVZ

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 l 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 possibl connotations of the anticipated effect of the absorption of lead ^from the ambient atmosphere. This matter of verbage, is not, of itself, imjiortan^, except, perhaps, us 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 lust paragraph of the introduction provides little comfort to 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 et ton, is not related to air-borne lead. . 01398 WS PM '/ W ji p * lfc i Ifp ff i y L J J P ^ < - v ../ .------ agSEr,. k J ; rercottaa * / 'Y' jv/ ' >-: V 'i- ' _ ' .... ' f ,,J . 7 / . / < / ' <.^ ~"0t d i ' . " ' ^ ' ' : 0 - . - 6 .l // ____t _ 30.5 " > 5:0 ' m i - ' r f ...... + -, 7-- -- ,th ~ 'l( f. / 5 / / ./ - ' / l ~ 0 ' / 3 2 roe4w 1 t ' " ........V " ;; 2 .V. ; 'i " >%' . ;\ b. 0 \. 'i U 76 .0 ;4 W : '. ;i ! /-' V-.' 7 ' ' .; ',.. tf'J : / r .o ff -. *>- ? 2 / - V. - ' Vf`` / Kt / m e r Per c *r fewa . ... ' ; ;T i f : ' h '/ .T ) ( f 3 o, -6 i- 3 . 0 2- .. 4 . 'ft _ _ _ i ' ' t - J . / l - ' / 5" j- ' .'.;-.:^,? . J , : 0 / - 6./7 jf-h / f : 1 i `r- ... . - " W ' . '` 1 V, 2 J' ., / ?' . ` y f- :r;' ,-.;rr" *,* ; L M iKri. r; T> ,V - y, y 7 .y 4 . 'i ' 2 * ': ^ P 3& i '/ ' ' . , -. .. U_ _2------ '--__--:---- - If Ct o> ! / f o ' Ico i 6 . ................-- -- . / . '. y ., ; : \ '-j * ': lo o ,o z z. . ; ' 1 - j.tffir fft e iif J v is J 'f U>J*j ^ O - d f l f u j h & -C n - t i L _ ..y ,>. . * I knHA~lfc O.ll * Oft4 ;... 0 (t t ; ^ 33 o .o t t : L _ 0 ' 6 6 ^ ", ' t , 0 .0 0 3 . . -V ".t- * > S' , 0 , 0 3 7 '.. .* 3^ 4 ' .* _ _ -rv CJjdlai^ J 0 , 0 0 ?____ j i j 0 , 0 3 <[ Table 12 Distribution of Y/orkmen Employed In Mixing Tetraethyl Lead with Gasoline ' ' I According to Milligrams of Lead per Liter of Urine . " (f ____ Milligrams of Lead Per Liter of Urine J f i s 27 \ 19.2 9 ........... 1931............. Composite Number Percentage Niimber Percentage Number Percentage Number Percen *0 -0 . 0 1 2 5.6 2 .- 5.0 19 l a . 3 ' 23 18 . 0.02-0.03 O.Oli-0.05 -J fc_ 11.1 1 1 30.5 10 25.0 8 20 .0 lit 30.lt : 6 . 1 3 . 0 .... 28 25 23. 20 . 0 0 6 ~0 0*7 - JL..... 25.0 -8 2 0 . 0 0.08-0.09 L k _ 1 1 , 1 6 15.0 0 .10 -0 . 1 1 -- 2__ ! 8 *3.___ _ :2 ___ 5^ o _ .. 0.12-0.13 2 --5 . 6 ____ 2 5.0 2 l lu 3 .-19-- .,, 15.1 2 . 2 1 1 ____ 5 lui h - - 3.! 0.lii-0.15 0.16-0.17 0.18-0.19 1 2 . 8 0.2 0 - 1 2*5 1 1 - , - . 2 ^ _ - .. l 2 .2 2 .2 2 # lu 3 :2 1 . 2 l. 1 o. ' 2* l. Totals - J 6__ 10 0 . 0 ho :loo.o k.6 10 0 . 0 12 2 10 0 . Mean Probable ;'rror of Mean Standard' Deviation : 0 .0 68 1 Ij. - 0.036 O.O66 - 0 .0 0 k 0.037 '.0.033 .... 0.055 04 004 00 0 . 1+ 1+ - 0 . 0 0 2 ____ = 0 *0 2 2 ___ 0. * Two results 0.32 and 0.61; Excluded in calculation of means. 01 400 Tabi 12 Dietribm tion o f Vorfcaan Xaployed In Mixing Tefcreefchyl Lad wlth Gasolio j |Acoording t o Mlligrame o f X>ad per L lt r o f Urin M illi grams Of I*ftd jf 1927 m $ ........... 1031 ........ Coaposlte Per Ititer o f Urine Humber Prenta*e Htoaber Peroentacc Huubar Farcente* Vuaber Peroen .. 2 3 .6 2 .. 5 .0 10 l i l . 3 .... _.23 1 8 .< g.*2?-it&5___ --.--,. i * i - i i : 50.5 Jto _: 8 ...... . 2 0 .0 lk 30.k 28 .. iS9.`< 6 1 3 .0 .... . 25 ^ 20 . 0. 06*0.07 _ J L _ 8 . ao.o 2 k.3 1 5. 0. 08- 0.09 6 1 5 .0 - .. 1 ... 2 .2 : 1 1 9 . 0. 10 - 0 .11 0*12- 0.13 8 .9 i .. 5 .6 ...2 - 2 .... 5 .0 5 .0 * . - 5 b ' -^ 3 3. Ili--0.19 ..... ) .18- 0.19 _ L _ 2 .8 1 - J U & ...... JL -- 2 .5 1 2 *2. . _ . a 1 - .________ _ 2 -- i 6 1 5. 20* 2 ...f c J L . 2* ~ 1.6 Totale 36 .... m & ~ . Ji&___ 10 0 .0 .k * . . iooo / *oo' ( Mean Frobable !3rror of Mean Standard DeTiatlon 0 .0 6 8 ......... .... 0 .0 6 6 - O.OOk -- -- ... - 0.00U - 0.096 - 0*097 ...... .... .0.033 . .... _ - 0.303 -- 0 . 09lt Two re su lta 0 *32 and 0 . 61* xoludt in o a lo u la tlo n o f meana . 0 .0 5\5 _ - 0.002 _ 0.039 01 4 nu 1 Tabi 12 DistriLbbittlloon ef Worrkkzaseen Snplojsd In Mix3Ina Tstraathyl I*aad wltb Gasolina t ^According to Xllllgrana of Lead par llfcar of Urlo H i l l 1gram a J 1 9 2 ? -- | 1929 C onposita O f &oad te r L ite r o f U r i n a . ..... M u a b a r F s r o s n t * * * S t b r P a r a a n t a K * * u * b r P a r e a n t a K # I m b # r t e r e e n . * ...- 5 . 6 2 .. 5 . 0 1 9 .... _ i l i . 3 1 _ 2 3 ; h _ - i 8 . L .... 10 2 5 . 0 ..... .....l k 30 .li 28 -1 1 _ .8 2 0 . 0 _____ 6 ..... 1 3 . 0 .......... , 2 5 _ : 2 0 .1 0 .0 6 -0 .0 7 9 .... 2 5 . 0 ... _ . 8 _ 2 0 . 0 .. ... 2 l u i ... 19 1 5 .1 0 .0 8 -0 .0 9 0 .1 2 -0 .1 3 _k 3 2 .. 6 8 . 5 .... .. 2 5 .6 2 1 5 .0 .......1 . - .. 5 . 0 5 . 0 ......... * ::-r!9 .i . 5? 3 . k .1 O .l l i --0 . 1 5 1 2 .5 1 2 0 . 1 6 - 0 . 1 7 .... 0 .1 6 -0 .1 9 h Jh 1 .... 2 .8 ...... 1 . . . . .. 2 . 5 1 JL - j f e L _ l u l ------- _ 2 L . - iii 0 .8 .... _ S ____ JlfiU -- 10 0 .0 1*6 _ 1 2 2 * 2 ____ 12 2 -- j s a i i / Jean ru b a to la 'm i * o f fean S tan d ard 0 .0 6 8 _________ -...... 0 *0 6 6 ....... .. _ ... 0 . 0 5 5 .... ......... . i .............0 . 0 5 5 - o .o o U .......... 4 0 . 0 0 5 _______ * 0 . 0 0 2 ......_ - 0 . 0 8 1 ... ................ 0 . 0 5 7 0*0*1 _____ 8 * 3 2 2 _____ Tao resulta 0*32 snd 0*64 sxolttdad In oaloulation of aaans. 01 4 0 2 w.. : ^\' ' ' r V H - ^ / V-u / \ 1 :/ \ ^.y\&f '^ f r W / v w ^ ^ J M ^ a s u U t V y V / A - / V ~ 1. y 1. jt-IV./j V-/ Ppl^ttfjclc '{jjton ^T?W?(Erro rafear +:0.,i z ^ ',?; i :'v til^kM''''1 0-1- Q 3 - -... 5.0 f 4, 4 o . r - :; ; -\ '''ill 0. v*! . ' ; 0*54- - i 0.51. Il ;^. ..-. . '..rSJ Jll^^ar eifusJ-to ^ *X.Q'%f$& '" '...- _-.. . ..'.-,Ci'.-.iiitLiv J-.ulgrf.^-- a,***> rWi ~V" 'VW - ' f , : ! : .) ?, i*.&*^j*S 2?T11_i*-V** .Wi* ^*j f sfa *,v"- %&a ,'? ymm B stSra V-S VSj m :' i..'. ^Vy-^- %' ;' fates W3I BKSRS/ r:i'S SAPVS W<<-4 c<\i V f; )K*<Q-fltfl , ..'*'^y.^'te.'j' V - /^--`-'**. 'j <s^ i ;V/. ** rS/i&AW.;-; %r# `.'>--'V-- /. -/ - fA ` ;-1 J i 'V* s. r-^p*VVUte *>-! n ^Uk . '. ;t. ' ipsf. r**A M M ferV li A - Vy frustini. '1>' V./ , 'A . i ' ^6^ 0V< V . ~ ; s~/-- - < i Usus*t :, ^ VM. -r '':*v/':" , *VV o i'xm&t-i ** C/ tr a g e OmLy Co n c e n t r a t io n o f Le/ ia /n F sc e s Fo r Su c c e s s // ? I/e e ^s Ce t e r Ce s \ 1.0 0 ^ -9 * k '90 0.85 K <, 0 8 0 k 0.76 ^ 0 ,70 jo 0.65 , 0.60 <0 ^ 0.5J (E, 0.50 $? 0.45 0.30 PbmFood Su b j e c t - - Su b j e c t /?* j.f > o.io k 00J 8 Si V: 35 7 9 11 13 15 17 19 21 23 25 27 29 31 Ti m e w We t if5 F e t e /? C e s s e t / o / v o f F^f o s u /^f M/ prsfMY Out put o f Leh o i n Uifin eor?Successive \ FtfsAf t f /?Ce fiwGEJfld'f Out put of g g o //vm eesFo/ fSuccEssi Wfe/s/Irrfr w M l/G fl/ Er(flGE DmLy CorfGNrf{ ATio n o r L eo o i n Ur i n e For? Su ccess/ i/ t Weed 's Af t e r C 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 (1.72 mg.) falls far short of what it must have been on the day following 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, .\ a new phenomenon appeared in the faecal excretion, which required some explanatfSTf!" 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 hut 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 A ,Ll.civ, ./v C\a. j,^*** ** ncTTM"-- -paranna. 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 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 tll^Mfinary 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 adminxstereu. The 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 in 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 phebomenon, 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. ft--* '-*,In 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 10 0 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, * j* l Any lost samples are so recorded. The absence of records on other days are due to failure of alimentary evacuation. Days marked at the top of~ 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. 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 istered in four doses daily, at four hour intervals, each dose consistin this in or- of five grams of MgS04 .8H20 dissolved in a minimal quantity of water. iginal . data. 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 fouhcl in ^the blood of the first subject for a corresponding period. However, just as the lead excretion failed to reach a normal level, so t 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 mail"woraevhat irregularly. They require no comment. AH i/ 8 117 I O T? / 0 ` / 15 3 / > ' / *Cq ' z ( i 'L V L ' V il -fVi >. h h v s :* i v ^ ^ \ - A) '/ ^ 2 )'/ ? j^ / i'4 ' 1 X * - t ;a ` . f / ---- _ _ _ . . - - ... . y . TT'i From the'desk of GRAHAM EDGAR ?<i h / L ti1 / i? 5.'-/'S V' ? J V / ./ c<9 i o 7 <-r4 'i.-z-S - 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** v 288,484,450 - 527,803,050 1,241,416,050 1,854,505,900 1,970,389,463 All Gasoline Consumed in U.S.* 29,075,858,000 ( > 9,437,188,000 /" { 10,698,787,000 / 13,549,879,000 5' ( 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. i . ' > '1 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. A A - </ ~ / / S/ / Z y 6 Y `7 ' * G 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 o r "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 nay 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 vrith which tetraethyl lead pen*-orates tbs pulno-iary epithelium. Under certain conditions, notably in the presence of sunlight, tetraethyl lead is unstable, breaking down J yield water-soluble, crystalline triethyl lead compounds. Slight agitati 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 v-'ith weeping and sneezing. The dangers associated with the preparation and handling of ite traethyl lead are fairly obvious, when these properties are recognized. Unfortunately, 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 C/'aUju.w *i , lead poisoning of the most serious type occurred, g.asa-c'iatad. wi-th the /'JuM- - -U-t<-4 1C sudden onset of cerebral symptoms and with a high mortality. - Y/ithcut entering into an irrelevant description of the (-various / Steps by which ilthyl 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 leeiwAn the part of workmen, and in the maintenance of conditions under which the vapor of tetraethyl lead is not present in the air bres.thed 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 e.nd in the avoidance of careless practices. - The hazards associated with the handling and use of the finishec product, Bthyl Gasoline, differ both in quality and quantity from those which 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 aeaffet substantiated case of lead intoxication in the the nine and a half years of its continuous use, up to the present (July, 1Q32J, in certain parts of the United States. This basis of dif/ f=rentiation is the more significant v/hen one considers that the hypoithet- 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 Gaao line contains tetrae.thyl lead in amounts so small that the solution has lost the essen tial toxicological properties of tetra.eth.yl 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 bo 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. J/~/ The importance of this fact is two*'fold. Not only does it indicate the improbability of the absorption of lead out of ,e:--.<v a\J r-vi '< Among the thousands of persons .in the United States engaged in the handling of Ethyl Gasoline or otherwise exposed to it3 possible dangers, fewer--tha-iy- on a- hundred 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. O n l y jthree have h iwiM ft.WS&&SGSBXE&, An oi vn- r e-semb'J to - r~r -1 tion b o egorAed..aa. CnUfisiioB- y \l h i ii.iuj k abJLeu, Goroful -ot-n cty L of thSt'e cases fallbiQ~i.Ti euchr-i-nstanee "to co tablieh- a-- satisfactorv basis for the Ai ognoni n -of.lead w a g o n i n g - y 'l Gasoline on the part of persons vho come in contact with Ethyl Gasoline, _ * bu t it also establishes the certainty that any minute amount of lead which might be absorbed would be unable to distribute itself in the fatt;, *y.*t' V ; tissues ana the nervous system in the manner characteristic of tetraethG i Vi 1 Z -, 5 lead v/hen absorbed at a 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 "3 ' -t ' the volatility of tetraethyl lead and the various gasoline bases v/ith -V .i"ji _ __ -i 1 jjwhich it is mixed, is so great that approximately half the gasoline may 0 ' (lasjj0 tdii be evaporated before dotoo-tcnolo a-ffloimt-o of lead .ass found in the vapor. -2 : ' - j -A ' It follows, ft?om t h i -a- ffao-fc, that the vapors rising from tanks containing ' ejj. ' `* ; ' Ethyl Gasoline do not contain dot g-.r-bvec amounts of lead. However, this -i ,r 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. .3 " s Although years of experience have not shown the existence of danger 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 appre ciation of the nature of these hazards is required for an understanding of the problem whil)*!" Jxey provide for investigation. ' E t h y l 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 come in contact with Ethyl Gasoline to a greater or lesser degree through spillage, as an unavoidable result of the various metiods 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 hosing, or by rai nfall ^ TL. ---- 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 /' > 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 fL nely divided inorganic lead compounds (chiefly lead bromide), which are deposited, in part, along phe exhaust . :s 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, ventilal 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-artretcmiiat'Tdn od--lead dust within the garage., .as ,a^resul-t-Q-f-- theehe-'factor'3 ," together _ ithr the settrtn:g~-o-3 -gag-...ia ~Idk^l'yJ t^he-~gre5Tly eamesriprf. bv that,whicih^ ieitranftLosf-rom-the""repair" of `electrical storage hatt-erlas,-- the- use of- pain ts" are?"cTd'er", and fr m such similar practices i-MTt r* i17-- thTV'T'Vpa_il` L'f aiftCmobrl-ggj tTP \ ,We must re gar a --U&asn <sjiutuf.M. '&U/ 2U/ cuH^kF-ifcu-to- i!y r ' r> f 80 .. (wgiagB.'gfc-s of 1 m d trinri,'r 111-131- 'l-- ^ V-- ^ Xx^.y p i o k rit ij---nirrmtg nnrl mireo r.-t ,.1' 4'W u --A f.v'.t*.,4X. *''*? -'t/' *' ?i-r c Cne further point must be 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. The 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 U 3 e 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 1523 in Dayton, Ohio. A few months later it was on sale in Cincinnati and in the district around Dayton and Cincinnati. Thence its use w a 3 extended oo 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 1526 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 !.iay, 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 TABLE Period of Distribution of ~"thyi G isolane Ir. arlous American Cities u'p to October 1'32S\ Locality Date of First D 5 ? tribtition Interval r/~ Years of Continuous Discontinv a'Ace Distribution 'ayton, O o f incingati, Chlo .. heeling, Vi.Va, Chicago, -` 11. Detroit, Mich. t. Lenir-, *o. lansaa City, Vo. i n n e a p o l i r ,Minn. ilwaukee, ft'is. 'altimore, H d . asoington, D.C. 1 m Antonio, Texas February 1923 April 1923 j} Summer 1923 j Autumn ; Autumn j Spring 1923 1923 1924 j Spring 1924 j Spring i ; Spring 1924 1924 j Syiring j Soring 1924 1924 Spring 1924 none none /fas' tr ' A 9&JS& same. earn Ht --wee. ?Ty lUuZ'zXjf L tremo ' :p seme- ' 5.7 6.5 \5mtd 3.2 3.2 3 ti 3.2 3*0 3.2 3.2 3.2 3.2 n m a h , Ga. . ij*Lrl ti)| r 0. /iclcs on ville, Pin. Autumn Autumn j Autumn 1924 1924 1924 none ( y none 7 none 5.0 5.0 ' 5.0 ( o'.v Orleans, L a . .Loveland, Op io j Summer Summer hilndelph! a , Pn . or-too, Pars. Summer stnawwi Denver, Colo. Summer 7an Francisco, Cal. Summer Los Angeles, Cal. Summer Spokane, V'/ash. Falsa, Okla. . Summer Summer 1926 1926 1926 1926 1926 1927 1927 1927 1927 none none none none none none none none none 3.2 O *`. o *2 3.2 --O ^*> n >) i- w ) :-l t<2i.<p2* 2 .2 1 ' Pew YorK City autumn 1928 none / 1.0 ! figures are available are shown in Table l . 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 1hat time, the lead concentration has varied in accordance with the quantity required to bring the available gasoline 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^proportions of"the problem vhich confronts us. r> ....................................... It 7is not to be supposed that the possibilities of danger in the general use of Ethyl Gasoline gone 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 associatediiUa. 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 i : ` . '- > the Bureau of Mines'^ extended,RywSfl 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 \ Approximate Gross and Comparative Consumption of Ethyl Gasoline In Various Areas Prom 1926 to JulyN)f 1929 19 26 Distribution Millions of Areas of the Gallons of Uni ted States Ethyl Gaso line . Percentage of Ethyl Gasoline to Total Gasoline T-- 1 92 7 192 8 Millions of Percentage Millions of Percentage Mi Gallons of of Ethyl Gallons of of Ethyl Ga ^thyl Gaso Gasoline Ethyl Gaso Gasoline Et line . to Total line Gasoline. to Total li Gasoline. New England States and New York. 8 .0 0.5 52.0 3.2 91.0 4.9 Pennsylvania 5.0 0.9 30.0 4.4 75.0 9.9 Atlantic Coast States Ohi o Kentucky, Georgia, Florida. Mississippi Alabama Louisianna Arkansas, Tennessee Central States Texas. Oklahoma Hocky Mt. States Vest Coast States TOTAL 7.0 1. 0 3.0 0.5 25.0 0 .8 2.5 0 .0 52.8 0.7 0.15 0.36 0 .2 0 .8 0 .1 0 .8 0 .0 0.58 6 .0 16.0 18.0 0.5 110 .0 4.0 10 .0 30.0 276.5 0 . 6 18.0 1.4 2 .1 93.0 10 .8 1 1.9 39.0 3.7 0 .2 8 .0 3.3 172.0 |,, f 4.9 0.5 8 .0 i 0 .8 3.1 16.0 4 *o 2 . 1 27.0 1.8 2.5 547.0 4.4 2 8 / TABLE i Average Tetra-ethyl Lead Content of Ethyl gasoline In Various Areas Of The United >tat*s from 1926 to 1929. Distribution Areas of United States. Dew England States and New York Pennsylvania .tlantic Coast States Average Tetraethyl Lead Content in Cubic Centimeters per 0 1926 1927 1nno 1929 --.4>J*. -1L*cw ' 1.7 1.1 1.0 i.e . ... 1.2 X.a 1.4 0.9 1.65 1.5 Ohio 0.9 r Florida, Mississippi, 1.0 m d Alabama Loui3ianna, Arkansas 0.9 and. Tennessee 1.2 i jl.7 0.6 1.1 1.5 1.7 - -- i ......... . ' 0.9 - j1.9 I i :1.3 i Central States n A 1.6 oc**ri>. / "' ' ........... 0.0 "exaa, u :lahon>a :ocky ^ourlaln States West coast States 1.4 1.3" -- mm 1.7 T !1 2.0 i 0.7 2.0 , -1 2.4 .4.9 2.7 2.4 X1 *w5 _ 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 f' to the United States Public Health Service, and to the Ethyl Gasoline Corporation, whose officials sponsored the work. The fourth of such field' invewtigations i3 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 --kaovsisid"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 ancf shall confine myslf 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-- / ' ~&i-- pnovirding an answer to one question. - Is the magnitude of lead expos ure arising from the combined hazards of the use of Bthvl Gasoline such 3.3 to tring about appreciable lead absorption on the part of any group of individuals in trnrr'"4 ~c In terms of the facts presented ir. pr*7 icu 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 2 . The Selection of Experimental Subjects. Table ^ shows the numbers and types of subjects selected, together with th* locality in which they were employed* The three croups of work men 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 hdd 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 1h 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, CincimwHrthp*Savannah, 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 D LOCALITY Locality Number of Number of Filling Sta Tank Wagon tion Atten Handlers dants Exposed Exposed to to Ethyl Gas. Ethyl Gas. 771 -- ~ 56 *101-- 150 Number of Garage Mechanics Exposed to Ethyl Gas. 301-- '501 Number of Number of Barrel Fillers Barrel Fillers Not Exposed to Exposed to Ethyl Gasoline Ethyl Gasoline 201 -227 *251 - ,7272 Cleveland Ohio Cincinnati Oh io 11 Dayton Ohio 11 Chicago Illinois 6 Detroit Michigan 1 St. Louis Missouri 11 Kansas City Missouri Minneapolis ''in 'esota c: > Cj~' Jr;cksonvill 3 Florida 6 Atlanta Georgia 10 Milwaukee Wisconsin Boston Mass. Wheeling W. Va. New York Mew York Total 56 1 10 9 11 , r> 8, 1 -- 6 4 50 15 13 15 13 12 ' 48 I 5 5 5: 5 51 50 10 201 27 27 22 22 well located filling stations had handled more Eth.,1 Gasoline than had similarly employed 'i&M 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 -at made up of one hundred and nine per sons who Nhavei been working on cars which used only Ethyl Gasoline, and an additional ninety-three who have been repaining cars of ^ i c h 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 Dayton, 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 which Ethyl Gasoline was the exclusive fuel. The entire group was composed of subjects who had been employed 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 cccupa4Afi&ltrel ationships to Ethyl Gasoline. The garage me char ic 'group is entitled to special ao nsideration 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 i3 for this reason that it was expanded to a large number at the expense of the less exposed groups. The barrel-fillers referred to in Table -1 vrere included among the subjects chosen for the present investigation for a specific reason combination of circumstances. Several years of observation of persons vr.ose occupation involved considerable exposure to gasoline varoused 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 / ( n 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 v/hich was. provided with an elbow, a flexible hose and a float valve. Kach 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 r e m i t from gasoline absorption. These men v/ere carefully exam! -ed In a manner wh'ch will bo described later, and several type3 A laboratory data were obtained, including the lead content of the urine and faeces.. (itl U y Nr*U**%i-**>f* .. **(,**-*.* -L*/*** * '{* " * Shortly after these examinations had been completed the refinery In question embarked upon the distribution of y.thyl Gasoline. The latter was handled in the manner described auove for ordinary gasoline. Inas much as experimental evidence indi cated that the hazards of lead absorption from skin contact and inhalation of vapor from gasoline containing tetraethyl lead were prac- totally negligiole, no fears were entertained as to the consequences of 1 the additional factor of a low concentrt ion 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 a 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 upcessary 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 any type. y 3 Methods of Study '? The facts presented in 391 earlier chapters Hilt Til wnT inii would seem to establish the relationship between lead excretion and lead ab- sorption<^j^>afsa!kody^9i,$>?^ 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 previous 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 HISTORY SHEET No. - Name ` Marital Residence Examiner*s 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 Dates Painting Plumbing Carriage, Auto or Car Type Casting ,, Smelting or Refining "Treating" Refineries Storage Bax. Mfg. or Rep. Lead Burping , Printing or Lithog. Mining ! Foil, Solder, Babbit,Mfg. Previous Lead Hazards Dates Brass Founding Soldering Enameling Paint Mfg. lottery Glass Polishing Cut Glass V7hite Lead Rubber Garage Telephone or Telegraph Rep. Automobile Owner . Gasoline Used Repair Work . 's Prev'ous Illnesses with dates and exact descriptions (no leading questions) Tbc. Malaria Rheumatism Lues. Gc. scarlet Diph. Typhoid Tonsillitis Frequent Colds Convulsions Heart Disease Asthma Significant Family History: ' . Remarks HISTORY SHEET (cont) No. Examiner *3 Initials Sleep Bowel Movements Hours in Bed Dreams Frequency Restful Hour Tendency to Constipation Cathartics Tendency to Frequent Stools Date Disturbed Teeth Usual Weight General Health Brushing when 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 Pains in Joints Muscular Strength Pains in Belly Appetite Digestive Disturbances Character Time Swelling of Joints Cramps in Muscles Character Different Meals Frequency Nausea or Vomiting ) / Skin Infection or Eruption General Hands Polyuria Nervousness Nocturia Frequoncy 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 PHYSICAL EXAMI 'IATIOil SHEET io. Examiner's Init. General Appearance Nutrition Pulse Temperature Color of Skin (exact) Date A/re Height Pos ture Musculature Blood Pressure (seated) Condition of Skin Weight Condition of Skin of Rands Cornea Nose Glands Mucous Membranes Teeth Lead M n e (Appearance and Location) Sclera Throat Tons ils -^ars (structure) Go ms Pyorrhoea Heart Apex Rate After 25 hops 2 minutes after R C .D. R.S.D. x trto Lungs: K.I. - R, L. D E i* R. y / L.L.B. - Chest Diagnosis Abd omen Liver hectum Spleen Genitalia Kidneys Upper Extremities Diagnosis and Remarks Lower Extremities !44 s NEUE0 LOHICAL ft:'AMI'iATIO fI Cranial Nerves I Smell Examiner9 Init. II Sight 111, IV, VI R - 15/ L - 15/ Condition Correction Extrinsic Eye Muscles Pupils Visual Field Reflexes V Motor VII Vili Audition It L Sensory Facies Equilibrium IX, X, Xll XI Neck Speech Swallowing Shoulders Tongue Jp'er Extremities /- Tonus ( Atrophy . Ataxia Tremor Muscular Power Dynamometer ' Stereognostic Epicritic -- Protopathic Kinaesthetid" Thermal Vibratory Nerve Trunk Tenderness Lower Extremities Reflexes Pharyngeal Biceps Triceps _ Radial Patellar Achilles Epigastric Abdominal Cremas teric Plantar Gait LABORATORY s h e e t No. URINALYSIS; Examiner s Initials Date Quantity Sp G . Reaction (Methyl Red) Albumin (Heller s) Sugar (Pehling s) Xcetone (Nitroprusside ) Microscopic BLOOD: White Count Red Count Heat and Acetic Ha omoglobi n (Dare) Differential (loo cells); Poly. Neutroohiles Poly. Eosinophiles Poly. Basophiles Lymphocytes Endothelial Large Mononuclear Transitional Abnormal Stippling per 50 fields Polychromasia ) / xAi.V,rAwTjVJ<LTxl TJ.fU* iAwT EXAMINATION; Accurate s'CSfPlSn&nt of '.curs required for collection of; Urine Faeces Constipation FAECES Wt. dish + dri3d faeces Wt. dish + ash Wt. dish Wt. dried faeces Wt. ash lead Mgs. Mgs./gram of ash Analysis No. Diarrhoea Cathartic (type) URINE Volume c .c . Lead Mgs. Mgs./li ter 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 ) / LABORATORY s h e e t :jo. URINALYSIS Examiner's Initials Date Quantity Sp G. Reaction (Methyl Red) Albumin (Heller s) Sugar (Fehlings) .Acetone (Nitroprusside) Microscopic BLO jD: YThite Count Red Count Heat and Acetic Haoxnoglobin (Dare) Differential (100 cells); Poly. Noutroohiles -Poly. Eosinophiles Poly. Basophiles r Lymphocytes ! /- Endothelial Large Mononuclear Transitional Abnormal Stippling per 50 fields ?o1ychrornas< .Accurate statement o~' ' Urine Constipation Diarrhoea FAECES . y.rt. dish + dridd faeces -Ht. dish + ash A't. dish At. dried faeces 'At. ash lead I'gs./gram of ash Analysis No. .aoccs 7% - J *L. Cathartic (typo) URINE Volume c.c. Lead Mgs. ::r h ./liter Analysis No. neo y palpation and by opposing the xaminer's strength to that of t 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 7 was employed throughout the tests.) Measurements of the blood pressure of each subject while seated, ere made with a standard manometric apparatus. A fresh specimen of urine wae obtained from each eubject and examined at once for its reaction, the presence of albumin, and sugar. Microscopic examination of the urine and a test for acetone wer. carried out only When indicated by chemical abnormalities or / by suggestive clinical findings. - Erythrocyte, leucocyte and differential leucocyte counts Q C'.K:ilC'.L, were made as a routine^ only on the barrel-filler group of subjects. Otherwise, such procedures were 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 L***' for the determination of their lead content. The collection and. the analyses were carried oyt 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. iwl rmniiTI^S. -v-.yj No case intoxication 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 were the complete absence of lead line, the lack of significant microscopic blood changes (stippling), and the striking^infrequency of vague symptoms of ill X l l u Lt x . Za-i u health, /f" this " e v i d e n c e s of significant load ab A_ sorption as a consequence of exposure to Ethyl Gasoline must be 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 . 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 expa^mgg^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. T.;BLE Distribution of Subjects According to Period "of Exposure to Ethyl Gasoline r -d . u 1 Period of Exposure In Years 0.1-0.25 0.5 1 2 3 4 5 6 Totals Pilling Station Attenda nts Number Tank *agon Handle rs Number < Garage Mechanics Numbe: df Biri^el Fillers'-, Hot Exposed to/ Ethyl Gasalia ys Number 4* Barrel Pill Exposed to Ethyl Gasoli Number < xf J8'' JT -O- S> -Or / 4 16 jy y i2 y xr /y & Q jy >4 s>/ 18 82 12 26 13 - k y Jc 48 36 18 Sor y Jc 6 ii 16 28 23 41 10 18 56 100 48 19 38 16 32 6 12 50 100 98 49 22 11 12 6 73 201 100 < ?.cy .1 -0'/ / - r- - o / ./- <r/ \\ 0 ' -O' J / / y jy oy 22 -e -c -a --o * 100 TABLE 's >/ DISTRIBUTION 0? SUBJECTS ACCORDING TO HISTORY OF PREVIOUS EXPOSURE TO LEAD OTHER THAN ETHYL GASOLINE e-escription of Lead Exposure Filling Sta tion Atten dants Number $ None 20 36 uestionable 8 14 Slight , 28 50 oderate jy 3evere ,o" ~o Total 56 100 Tank Wa, on landlers Number f. Garage Barrel Fillers 3arrel Fii; Mechanics lot Exposed to ixposed to Ithyl Gasoline Dthyl Gaso. Number ^ Number Number ? 18 36 X ' sr' 15 55 10 46 10 20 30 15 8 30 6 27 21 42 163 82 3 11 6 27 1284 1 X jy X jy- 50 100 201 100 27 4X $y jy 100 22 ^ jar 10 vf - A *. r>/ f.. / y / :H . ' 1 1 01450 The distribution of th subjects according to ago, seen in Table 1 ^ 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 no_t exposed to Ethyl Gasoline. The . J x.fj,', ; ' * -L-! c'-U-ii. * explanation of this s-ituetien in the latter group is undoubtedly y ;*\ dqgjdao the fact that this group was examined in the sun .er when ^ the inhalation of gasoline vapor was at its height. These non . 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 irfci ma ci.'n . (cf. Tables and r--' on pages 7 and ) In Tables T , : , and , the findings as regards blood pressui 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- TABLE 7 -. Distribution of Subjects According to Age p f Age In Years IS-19 Filling Station Attendants Number sr ai Of Tank Wagon Handlers Number $ Of P' JO-24 3 5 O'" jor 35-29 12 21 15 30 0-34 12 21 7 14 '5-39 5 9 10 20 -0-44 2 4 5 10 -5-49 5 9 5 10 -.0--34 4 7 36 7-59 7 13 12 :o-4 6 11 5-9 'V sf 36 o lotal 56 1 ICO 50 100 Garage Mechanics Number y 94 32 16 33 17 34 17 42 21 26 13 11 5 84 4 OLj 2> / & 1 -o ' 201 100 Barrel Fillers Not. Exposed to Ethyl Gasoline Nu-.ber < Barrel Fil Exposed to Ethyl Gaso Number if J' -O' o- 1 5 6 23 29 5 19 6 27 5 19 29 o * 23 7 31 14 29 14 o3 00 15 J ,0 i 26 -O /"N . 4* 100 15 Pr' 22 100 Jean 1 i .- robab i o -r^or of `ean 40.3 + 1.2 Standard Levi atior 13.07 38.0 + 1.1 i 11.28 34. 5 37.9 +u5 9 . 85 +1.2 3.75 } 59.1 i +1.3 S .34 if 4 q 04t w -, TABLE i Eistribution of Subjects According to Certain Subjective Abnormalities Type of 56 50 Pilling Stati on Tank V7agon Attendants Handlers Abnormality Number .+. Number < :ecent Loss 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 Gasoli] Number G"" jzr' Increased ,'ondcncy to 'a .1 1 O 1 O u* 34 2 7 XK -<r' 'roquent "eadache 6 10 2 4 rt*) 15 2 7 15 iccasional bdcminal 'T'-,rnD 2 4 2 4 12 6 1 4 15 -ccasi onal M restive "1aturbance /' ) :ccasional euritic noto a 3 "3 * 5 ,5 o 4 42 1 4 ,J0" -<r 7 3 P" a" ia. 5 15 'onr General 'ealth -- .0- o- - 1 1 a -0 .0 .<r TABLE -| Distribution of Subjects According to Certain Objective Abnormalities. Type of Filling Station Tank Wagon Garage Attendants Handlers Mechani cs onormality dumber fff Number Number cM nder- .ztrition 4 6 2 4 84 allor 2 4 'I 2 4 23 11 rritati on f Skin of nds 11 20 12 24 56 28 3ad ine erve Trunk ?nderneas CK 6 er li & or & 17 34 17 8 remora 20 . 36 21 42 71 35 on sory 1aturban 's 1 2 3 6 A 2 "tensor ires is 1 o 3 6 1 1 trophy of tper Extrerr lies 1 jnormali tie s Visual laid 2 24 mm 4 1 3 94 \\ \ 2 e- ! ,o rinary old ity 20 39 15 33 92 46 Ibuminuria 0 O' 49 63 Barrel Fillers Not Exposed to Ethyl Gas line Number 4 15 8 30 16 60 Or 3 11 8 39 r> ..... cr A' jy jy C y I ..0' ! o l4 J0" j y Barrel Filler Exposed to Ethyl Gasolini Number t 2 10 2 10 12 54 jy jy l5 9 41 2 ,10 ( j y J&r i 5 2 16 73 jy o i \ 'A TABLE I O Distribution of subjects According to Systolic Blood Pressure 31ood Pressure Pilling Station Tank ^agon Attendants Handlers Headings Number rif Number /; 80-89 & <y 90-99 1 2 O'- 100-109 3 5 2 4 110-119 IO 18 16 32 Garage barrel Fillers Barrel.pu: Mechanics Number J>/ Number Number - 11 SO .0 o- 42 16 8 s'0 1 f Jar' c ,^G 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 7 12 .4 8 18 95 13 4 18 150-159 2 4 r> oo 4 5 2 1 4 r -0- 160-169 f' 3 6 4 22 7 JQr -O' 170-179 1^ 2 .or 0- -Q .0' oar 1 5 130-189 *2 ' 4 / 2 4 2 10 o Information 3 5 ....A _ 8 1 1 0 Total 56 ICO 5.0 1 0 C 2 0 1 10 D 27 o0 100 .-0" 22 -O' -0" 100 'em ?robable ^rror jf Mean 1 3 0 . 1 ." ... 1.7 Standard deviation 17.86 j iO0 *4 j 1.9 19.30 1 L E * 7 , 1 1 0 .7 ) ! 15.10 -L'-t 1.8 13.59 129.1 2.3 15 .86 (A. . J- i 01 4 TABLE II Distribution of Subjects According to Haemoglobin in Blood aemoglobinometer Pilling Stati or Tank ''agon Attendants Handlers 3adir.g (Dare) 60 - 67 Number 0 </* V Number 12 Garage Barrel Fillers Barrel Pill Mechanics Not Exposed to Exposed to Ethyl Gasoline Ethyl Gasol Number of Number W Number *4 sr or 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 92 - 99 3 Informat\on 15 27 59 .SS 27 54 92 46 1 5 10 15 7 or 1 24 O1 4 11 50 er 1 5 4 J*r AS stai 56 100 50 100 201 lot\ 27 100 22 100 s "ean 80 9* 85.0* 84.5* 71.1* 83 .3* Probable error of dean + 0.67 + 0.59 + 0.24 + 0.92 + 0 y1 standard deviation 7.39 6.1.. 5.09 6.98 6.34 * All means calculated on a wider grouping of readings. I 014 TABLE -' Distribution of Subjects According to Stippling of Erythrocytes lumber of itippled 'ells Per 10 Fields 0 1 2-5 6-10 11-20 21-32 :>tnl Filling Station ^'ank Wagon Garage Attendants Handlers Mechanics Number of Number Number Barrel Fillers Not Exposed to Ethyl Gasoline Number 36 64 33 66 159 79 7 26 .6 11 8 16 19 9 1 4 6 11 5 10 17 8 6 22 35 24 533 11 35 12 1 14 15 24 12 -or' sr 6 22 56 100 50 100 201 100 27 100 Barrel FilJ Exposed to Ethyl Gaso] Number 3?. 21 9E 15 T ' J0 Or -0 & -0 pr -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 ? 5CI`- nificance. The low results are of no 'hiTjioaa.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 U'.'f l/K Table ia; 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 M record the observations on the strength of the grip of the left hand and right hand, respectively, of the s I subjects. The frequencies and the means do not show any very / striking differences between the groups, except^'Irefareir that the barrel^fillers as a whole, gave a somewhat weaker response to the test. . The facts obtained from the analysis of the excreta of the subjects ane j . A survey of the tabulated results shows that a few high results are scattered - Irregularly through the data.-- i"' ~*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 ilndings in the computation of mean values increases appreciably the probable error TABLE O .2 *' Distribution of Subjects According to Strength of Grip of Left Hand land ' Filling Station Tank Wagon Garage Attendants Handlers Mechanics Dynamome tei1 Beading Number . d/fj Number 4 Number of. 50-59 ST" er" 2 4 4 2 50-69 1 2 24 3 1 Barrel Fillers barrel Fille Not Exposed to Expo sed to ^thyl Gasoline Ethyl Gasoli Number Qr rS Number % er 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 IS 6 12 42 21 6 22 3 14 110-119 2 4 o 4 20 10 2 7 4 18 120-129 1 2 7 14 25 12 0^ -O'" 1 4 150-139 140-149 150-159 160-169 J3" 00 5 31 4 'or" ST 1 Oo 5 3 (V er f V *r r>. >/ or 12 1 1 .O-' or". . QT J2T 0- <y ,cr .0 1 2 1 sr 1 er er No InformatioT3 22 39 10 20 ! 9 4 .......4- !7 - 15 _ ef cr 1 lotal 1 56 ICO 50 100 | 101 a.rV\'. j! 40.*7i n V(iav- ' 4n..w ,100 lean Probable Error of _____ Standard Deviation 95.0 1-9 .. 16.63 101.5 +2.4 22.75 , 102.9 91.1 +0.9 19.37 + 2.7 19.05 1 95.0 +2.4 16.51 Distribution of Subjects According to Strength of Grip of Eight Hand Hand Pilling Station Tank Wagon Garage Attendants Handlers Mechanics Dynamometer Head ing Number 1 - Number +4 Number ft 50-59 03" 0 jr 0 50-69 O J0 jy r ' 1 1 Barrel Fillers Barrel Pii; Not Exposed to Exposed to Ethyl Gasoline Ethyl Gaso Number Number < 2 7y A &' j y 1 4 70-79 sy 2 43 23 il y 30-89 35 4 8 9 . 4 1 4 7 32 90-99 8 14 6 12 29 14 4 15 2 9 r:c-ic9 48 7 14 40 20 3 11 2 9 110-119 7 12 5 10 28 14 5 18 4 ie 120-129 130-139 110-149 150-159 160-169 5 3. o La ^0 9 5 o -0 6 5 I2 /O 1 12 33 10 22 4 ` 19 16 - 11 10 4 7, 3 21 1 3 1 1 jy .0 No Inf ormati o:1 23 41 10 20 9 44 Total 56 ICO I 50 ICol 201 100 1 27 11 3 42 41 jy __ __ j ^ 15 ' loo i i i 1 i ! Q 0 oo La 14 9 4 -o -0 -0 10 Mean !---------------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 to i o CtDo TABLE /$ Distribution of Subjects According to Lead Found in Faeces Milligrams of Lead Per Sample of Faeces 1 - 0.079 '.08- 0.159 -.16- 0.2.39 .04- 0.319 .32- 0.399 .40- 0.479 .48- 0.559 .56- 0.639 * .34- 0.719 .70- 0.799 .30- 0.879 .83- 0.959 .96- 1.039 .04-1.119 .12-1.139 .00- + ' 0 ^formation otal can robablo rror of ean tandard eviatinn Filling Station Attend ants Number 6 5 12 4 ' 8 rt 11 9 21 7 14 Tank Wagon Handlers Number 1 O 48 43 S 12 6 12 j Garage Barrel Fillers Me chani cs Not Exposed to Ethyl Gasoline Barrel F il Exposed tc Ethyl Gaso Number afti Number < Number iAf 5 3 >L y O' 0 26 13 ' 4 "/S' 2 33 17 . . 9 9 4< 05 12 3 .. U _.. 5 23 14 4 /r 1 2 5 2 2 1 if ,-rWV' .1 if <3 \y 4 14 1:2 ! <3 !Ji _ ,y 1 , 2 f ! ,0 ; ! 0_ :C 2 4 IV ! 5 10 13 i O 4i 8 !' 1 !21 7 1i J& J ! 7 ! 1& ! ,O . 1! 1 *S ! i ; .O' i 1; 3 0 i l j ;2 *t : 3" : 0 3 9 3- h 2 s r i4 / _ 4. i i 1 J2T K*jZ 3 . O' 3 01__ 1__ & ________ o- jj 1 2 : (y^ & 1 1 *' 11 | f " 4L 0 !1 j ___. i____ ___ i___ r --% ; 0 iO i ;o 9 5 er er a' 5 J 'Cf' CT ! ..o2-/- 13 ~,r ' 4 22 ! o !' -o i. .i i -a 1 & i 1* ) 8 i n-`- : 3 . * 17 !i ji ! 34 i 13 ! 1 j 6 ! O' Id jj J^--' ! ; <0 !o i, i- L. . 0 a SU 5 ! 56 100 o ^----------------------- C.253 ! 50 ! 100 r1 0 . 260 201 !100 0 . 379 27 iO 0.380 9 0 100 0.233 y +0.018 +0 . 023 0.197 +0.012 0.245 +0.037 0.266 +0.024 0.160 TABLE l (< Distribution of Subjects According to Lead in Milligrams per Gram A3h of Faeces Milligrams of Lead Per Gram of Ash Filling Station Attendants Number rt Tank Wagon Handlers Numb a]. d : 0-0.039 10 18 24 Garage Mechanics NumbeI. d 52 Barrel Fillers Not Exposed to Ethyl Gasoline Number 1 4 Barrel Fil Exposed to Ethyl Gaso. Numbe:1 oA'*/ err -.04-0.079 14 24 16 32 1 51 25 9 33 7 3S 0.03-0.119 9 16 4 8 1 54 27 7 26 8 3e 0.12-0.159 0.16-0.199 0.20-0.239 4 2 1 8 4 2 3 6 j 36 13 3 3 6 j 18 9 2 1 1 2! 8 4 1 11 7 4 29 3 14 29 ^.04-0.279 -'.28-0.319 1 1 2 2 o o 1 2 j 4 2 1 -- -4- .-- J0 wO X \ 0 V { 6 32-0.359 .36-0.399 0 0 Q 0 0Q < 00 111 er Jd ' 40 * jy 0 o' :.40-0.439 44-0.479 0.48-0.519 0 0 0 0 12 0 00 "1 1'l " 0 0 t0 y2 5 2/ 0 er 0 7 0 0 Q; 0^ 0 s. 00 j.56-0.599 0 0.04-0.679 0 ' "0- + i l-:- :;o Informa tier 13 Total 56 0 c 22 100 l2 .(y -O' * 1* > 17 34 50 100 <r Jd i 3 !1 I !-.< 1 1 0 0 0 13 6 jy 201 1001 27 0 1\ 1 00 ' o 1! o' 0 .. . 0 100 0! 0 00 oo 100 'lean Probable -rror of "ean Standard _Devia tion 0.087 1 0.007 0.065 0.120 0.123** 0.131 0.137 - 0.014 " 0.115 i 0.0C4 - 0.005 ' 0.074** 0.100 0.014 0.106 ------\-1----0 .113 1 0. 007 i j 1 0.052 TABLE /7 Distribution of Subjects According to Milligrams of Lead Per Liter of Urine "illigrama ^f Lead Per Liter )f Urine Pilling Station Attendants Number .4 Tank Wagon Handlers Number /j Garage Mechanics Number Barrel Fillers Barrel Pill Not Exposed to Exposed to Ethyl Gasoline Gasoline Number Number 0-0.039 ..m 32 . _ 11 22 4fi 22 2f> A 3fi .04-0.079 -15 27 . 18 3fi.. . 7fi . 3A 1fi fin in 4 fi 0.03-0.119 . .13 23 4 .8 34 17 fi 1A 2 Q .12-0.159 _ _ ...3. fi 1 .2 ... . In . A _ a n .1 fi .15-0.199 . _.3 5. P . fi o .. ..0 n n fl '.20-0.239 ____ ]____ ____ QL__ __ LI__ .. 3 ..1. . n . 1-- '! :.24-0.279 ' O 0 ____ 3_____ 2__ ._ . 3 1 0 -.28-0.319 i O 0 1 .2 ' 3 1 _.0 .22-0.359 ; 0 I " ' . '.25-0.399 ' O r .* - .40-0.439 < 0 .44-0.479 1 0 ">.48-0.579 .. 0 P.52- + :;o In forma tier. ^ r..\. Total 56 ...0 . ...1 . 2 11 .0.. . .Or' . -.. 1 1 *./ _-_-_-_- --0-_-_-! _ 0 .. 1 1 0 .z. fU O .. 1 1, 1 . 0 ___ 1 0 1 !-_-_-L-_ . !1 ' . .1 1 ' __ I 100 ' . l-i'-r-! I 10 i 20 ( j 5 0 ! loo ; 1 j 3 4 . soli ice 0 0 r\ o 0 27 n _ .n ... . ) 0 0 / n .. 0 ..0r ...,,1. .0 0 G 0 .0 0 a__ 0___ ! 'n i 0 0 n Q O. i0 0O o -* 0 ' 100 1 22 1 100 Mean 0.071 0.039 0.086 Probable Error of 'lean io.005 io.Oil Q.0C4 Standard Deviation 0.050 0.099 0.079 * Man calculated on a wider grouping of findings Excluded in calculation of means 0.058" io.009 0.071 0.052 i 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, ;V 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 ouitabl-y.largo oample ugnlalm fi V'oT- 'P " 1 n .el por. 1 * ...T ,h o aertflin that-Lend han..1nf n nn-t , unleae"-4H^ m tbjtrgt,*'ihayvTrbeerbedCTiTery,j^^gy*'Tmmtfi -lao- , . 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, as compared to normal persons occupational lead exposure. (Cf. 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, 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 thtf 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 tv/o 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 hs meaning that there was no significant lead absorption as a consequence of this severe exposure. Thus> /. - ' it seems qui te 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 less) is shared by man. In view'TxPThe 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,7*MtA l$1* *J*t**v< show the results obtained in 1927, in the study of groups or persons who had not been exposed to the conditions associated with the use of Ethyl Gasolte . The medical student group differs from that aprearing in Tables TABLE !'{ Distribution According to Age of Groups of Subjects Not Exposed To Ethyl Gasoline, Examined in 1927 r] 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 0 100 .\ Filling Station Attendants and Tank Wagon Handlers Number iA41 11 18 16 23 20 16 14 11 10 13 11 10 9 10 9 54 44 33 114 - 100 Garage Mechanics Number 2 2 12 12 2 4 1 0 0 0 0 35 /. :4> 6 6 34 34 6 11 3 -o . 0 0 0 0 100 :'ftan Probable Error Of Mean Standard Deviation 22 .3 +0 .2 2 .3 37.5 +0.8 12.54 31.2 +0.8 6.69 TABLE ;J Distribution According to Certain Subjective Abnormalities of Groups of Subjects Not Exposed to Ethyl Gasoline - Examined in 1927. Type of Abnormality oecent Loss )f Weight Increased >ndency to 'atlgue )ccasional 'oad ache )ccasional abdominal 'ramo Occasional digestive Hsturbance occasional yeuritic Symptoms oor General ealth 71 Medical Students Number 7 10 9 13 15 21 11 11 -cr ^0 23 69 Pilling Station A t `endnnts 42 Tank Wagon Handlers Number n/f1 ' Number if r) 11 25 12 17 5 12 17 25 7 17 23 -" 8 12 57 34 10 / 2 24 J / 5 00 35 Garage Me chan ics Number i f 5 14 5 14 18 51 4 12 13 i# B 01467 TABLE O Distribution According to Certain Objective Abnormalities of Groups of Subjects Not Exposed to Ethyl Gasoline - Examined in 1927 Type of Abnormality 71 Medical Students Number f Under-nutrit Aon 7 10 Pallor 1 l irritation of sk i n of Hand s Or -er uead Line Jremors S* 2 -0" 3 Sensory Disturbances 3 4 Urinary Acidity Albuminuria i7" / 1/ 10 1 69 Pilling Station Attendants Number t '' 42 Tank Wagon Landlers Number it 35 Garage Mechanic Number *1 13 19 34 00 JO o- -0" o- -0 " -O'"' 23 0 -'0' 9 13 9 13 * 34 .3 4 sy a- 4 4 10 3 JO- G- 2 51 16 38 8 3 73 11 9 0- 3 23 9 \Ci 01 468 TABLE >I 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 at 100-109 1 i 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 ' 2OC-209 0 0 210-219 0 0 220-229 0 0 ' 230-239 0 0 Total 71 -* MfcOO Pilling Station Attendants and Tank Wagon Handlers Number if 2 O* 15 13 32 28 29 25 15 13 97 2o 11 11 33 33 11 J> 1 114 J0 - - 1 100 Garage Mechanics Number 6 14 7 5 3 0 0 0 0 0 0 0 0 35 * J3r17 40 20 14 9 Q 0 0 0( 0 0 0 Cf 100 Mean Probable Error of Mean Standard Deviation 125.9 0.8 10.20 138.2 1.5 23.45 129.8 1 1.3 y 10.98 table " ^ Distribution According to Haemoglobin of Blood of Groups of Subjects Not Exposed to Ethyl Gasoline, Examined in 1927 Haemoglobinometer Heading (Dare) 60-64 65-69 70-74 75-79 30-84 35-39 90-94 95-99 100-104 l-'-5-109 Total Medical Students Number < Filling Station Attendants and Tank agon Handlers Number | * Oarage Mechanics Number 1 1 ST' -0" .o - 0 1 11 1 o- o 0"' -0' 9 3 4 12 8 11 l3 oS 10 15 17 16 6 18 21 30 43 40 17 25 15 14 12 10 35 29 11 16 9 8 39 5 72 2 '0 0 1 1 . ... 9.:..... j ,Q-- J&- ,-o~- 70 100 108 / 100 34 ( IOC Mean Probable Error Of Kean Standard Deviation 89.8 -+0.6 7.78 86.0 +0.5 7.15 89.0 s +0.7 5.73 TABLE : 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 *4 Pilling Station Attendants Number 4 0 - 0.079 . IV ... 25 14 20 0.08 - 0.159 15 22 14 20 _q,.16_ - 0...2-5-9_________ 19.. 27 18 25 1 0.24 - 0.319 6... 9 7 10 0.32 - 0.399 . O.40 - 0.479 *5 o3 7 10 68 0.48 - 0.559 ..... 2 3 1 1 0.56 - 0.639 11 -0-" 0.64 - 0.719 11 1 1 0.72 - 0.799 -0" -0" 0.80 - 0.879 0.38 - 0.959 1 ... 1 . 11 1 0 1 0' 0.96 - 1.039 1.04 - 1.119 1.10 - 1.199 1.20 + .... -e1 1 -0"1 .0 1 x>-U0 3-:'- -eT' o -e 4 Total 70 100________ '72________ 100 Garage Mechanics Number 5 7 2 2 19 27 8 5 3 11 2 o"i. 14 00 00 0 o. 0 /" w 1 00 ; 0 o' 3* 11 26________ 10C Mean 0.232 Probable Error of Mean -U - 0.019 Standard ^eviati on 1 0.0236 ^-Excluded in calculation of means. 0.197 + -0.013 0.159 0.235 0.029 + 0.205 TABLE y ' > Distribution According to Milligrams of Lead per Gram ash of Faeces Of Groups of Subjects Not Exposed to Ethyl Gasoline, Examined in 1927 Milligrams of Lead Per Gram of Ash 0 - 0.049 0,05 - 0.099 0.10 - 0.149 C .15 - 0.199 0.20 - 0.249 0.25 - 0.299 0.30 - 0.349 0.35 - 0.399 0.40 - 0.4 49 0.55 - 0.599 0,65 - 0.699 1.50 - + Total Medical Students Number ef Filling Station Attendants Number 29 43 29 41 16 27 26 31 9 15 3 11 35 46 1 2- 0 -0''" 9 0 0 i 0 11 11 jr' i` i 0 0 60 2- 24 0 0 100 1 'y 0 J /0 2** 71 i O' 0 2 100 Garage Mechanics Number 12 6 1 2 1 1 1 0 0 0 n Or' ' 26 46 23 4- 3 4440 f 0 3 O'" 100 Mean Probable 5:rror of bean 0.079* -0.008 0. C77n - 0. 006 's -,, . 0 C`8o & O *131 t r .012 9 - 0 .023 Standard Deviation 0.094 0. 071 .085 0 .177 * Mean Calculated on a wider grouping of Findings Excluded in Calculation of Mean Calculated after exclusion of two results over 0.65 milligrams ,A r - i y 4 /0 TABLE > ( TT 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 ^rine Medical Students Number pf Filling Station Attendants Number y"> Garage Mechanics Number 0.- 0.029 11 . 17 . .... 11 1 5 .. ... 8 31 . 0.03 - 0.059 22 . 34 20 .28 .4 15 . 0.06 - 0.089 16 . 25 .. .. 17 24 .. 5.. ... . 19 0.09 - 0.119 10 15 68 2 8 0.12 - 0.149 1 1+ .. 4 . ... 6 . 5 . ... ... ..19 0.15 - 0.179 0.13 - 0.2C9 1 1+.... ____ 3... 4 0 / 1 1+ . . ... 5 _...7 .. . ..... 0 0 .0 0.21 - 0.239 0.24 - 0.269 1 1+ Qr er' 0 0 . . J o ... . . 0 ..... i 0 1 4 0.27 - 0.299 />'9.45; - 0.479 '1 .0 1+ -O' 0Q 1 1+ 0 0 0 ) 0.54 - 0.569 0.66 - 0.689 ' O' 1* 1+ 1 1 + 1+ 0 0 0 1.00 - + ' jO 0 3* 4 1 4 Total ' 65 IC O 72 100 26 100 Mean 0.078 robable Error of ean 0.007 tandard Deviation 0.089 Excluded in c alculation of means 0.081 0.006 0.069 0 - i 01 474 0.077 0.008 0.059 1 .XI11 and XIV, In Chapter 1 1 1 , 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 ordinary gasoline are ^Lumu'iid 'liegirtmm; 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. Table 1 summarizes the mean values for all the groups of 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 fact^must be made from the tables of distri- .'U.'.'Cu'-*3 bution.) Comparison of the means a striking lack of statis tical differentiation of the groups. The medical students show a significanti?, difference in age, but in no othr factor. Hie barrel fillers not exposed to Ethyl Gasoline show a significantly low haemoglobin content of their blood, as previously pointed out.. The TABLE 2 7 Summary of Mean Values of Age, Systolic Blond Pressure, Fnri.ioglobin, and Ex In Faeces and Urine, for Various Gvov-: of Subject Description of Subjects. Age In Years Medical Students 22.3 Not Exposed to Ethyl Gasoline 0.2 Systolic Blood Haemoglobin Pressure Readings (Sitting) Lead in Mgs. Leiad in rgs. In Single per Oram Ash Sample of In Faoces Faeces Lead i Per Li of Uri 125.9 0.8 89.8 0.6 0.232 0.019 0.079 0.000 0. 0. Filling Station and 1'ank ^agon Handlers not Ex posed to Ethyl Gasoline -Examined In 1927 37.5 0.8 Filling Station Attendants Exposed 40.8 to Ethyl Oasolin 1.2 Examined in 1929 l'onk Wagon Handlers Fxrosed to Ethyl 38.6 ^nsollne .Examined 1.1 in 1929. iarage Mechanics lot Exposed to Ithyl Gagoijno examined in 1927 31.12 0.8 Jarage Mechanics"" xposed to Ethyl 34.3 asoline .Examined 0 . 5 n 1929 !arrel Fillers 'ot Exposed to thy.l Gasoline 37.9 1.2 arrel Fillers x osed to 39.1 138.2 1.5 130.1 1.7 130.4 1.9 129.8 1.3 125.7 0.7 134.3 1.8 129.1 86.0 0.5 ' 0.197 0.013 ^ '0.077 0.006 _ 0. 0. 80.9 0.67 85.0 0.69 88.0 0.7 84.5 0.24 71.1 0.92 83.3 0.258 0.018 ..... /0.360 ttv023 0.235 0.029 0.379 0.012 0.380 0.037 0.288 0.087 0.007 0.120 *o; I 0.131 0.023 0.131 0.005 0.137 0.014 0.113 0. 0. 0. 0, 0. 0. 0. 0. 0. 0. 0. mean lead content per sample of faeces shows certain statistically significant variations withi- the g r o u p s ^ b u t 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 ir. 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 lead excretion of these subjects as separate group-s--and in combination. The results are seen to be slightly lower, but no significant statistical differences'ha*/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 -she!*>themselves 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. .1?/ TABLE :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. Filling Station Attendants Exposed to Ethyl Gasoline Tank Wagon Combined Handlers Filling Station Attendar Exposed to and Ethyl Gasoline Tank Wagon Handlers Lead in Milligrams In Single Sample of Faeces 0.338 + 0.043 0.277 + 0.035 0.336 + 0.030 Lead in Milligrams Per Z-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 19 15 1 34 / ( It would appear that an examination into the relati -nshlp between length of service and lead excretion, might ,'g4rve; a 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 2-1 . 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 ,-/ , and The mean values are summarized in Table S 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. c1" Factors Correlated Correlation Coefficient Length of Continuous Service as Garage Mechanic with Lead in Faeces in Milligrams per Gram of Ash. +0.017 0 . 0 5 6 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 0.099 (' t a Sl e 3$ Distribution of Identic.'. 1 Subjects For the Years 1927 and 1929 According to Milligrams of Lead Fbund in Faeces. Mil ligrams 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 Number 1 53 15 6 30 3 15 2 10 8 40 3 15 J&' 2 10 3 15 1 51 5 1 <r" A3- 1 5 2 10 1 5 1 50 0 sy -er' 0 ./' ! 0 -e 0 0 -0" o; 0 0 er 0 0- 1* 5 0 0 rH 50 0 20 100 20 100 Tank "agon Handlers Exposed to Ethyl Gasoline 1927 1929 Number Number 02 3 17+ 2 4 23+ 3 3 17+ 3 2 12 1 3 17+ 3 r T -er' 1 2 12 1` 0 0 900 /0 0 0 / 0 0 '0 00 0 0 '0 0 0 0" 17 100 1 17 I Mean 'robable Error of Mean tandard Deviation 0.280 0.030 0.187 >f< Swuiii >a ? "r"':ilr^ cl WUW. 0.236 0.023 0.153 0.308 0.025 0.150 0 ,3G O.oz 0.40/L* 0.036 0.2/5 distribution of Identical Subjects for the Years 1927 and 1929 .,,ccording to Milligrams of Lead Per Gram Ash in the Faeces Si 1ligran3 of Lead Pilling Station Attendants ?er !r' r. c: =-oh Exposed to Ethyl Gasoline 1927 1929 Number Number - '.239 2 10 1 5 i - 0.079 5 25 7 35 o - 0.119 5 25 6 30 ' .10 - 0.159 3 15 3 15 '.11 - 0.109 1 51 5 O.'O - 0.239 sr e 1 5 - 0,279 11 51 5 1. 3 - 0.319 0.02 - 0.359 !0 ' 53 - 0.399 ( 0.10 - 0.439 ^ 0 y 1 00 0i b 5d Q d 0.44 - 0.479 0 0y 0 ( 0.57 0 00 b 0.64 1* 5 0 1.36 1* 5 0 0 Total 20 "loo 20 100 Tank v,Qg0n Handlers Exposed to Ethyl 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 1 0 0 0 0 Q i S O' 0 00 0 0 00 0 0 00 0 00 6 0- 0 0 0 0 00 0 17 100 17 i 100 Mean Probable Error of iean 0.11S - 0.106 0.015 - 0.009 0.109 0.008 standard Deviation 0.093 ^Excluded in calculation of mean ti .4 '.-a# ' ' )' ) 0.058 0.047 ,i "'*'**'* o. //? i. O. OJO 0.142 ^ 0.019 0.117 TABL Distribution of Identical Subjects for the Years 1927 and 1929 According to Milligrams of Lead Per Liter of Urine Milligrams of Lead Per Liter of Urine Pilling Station Attendants Exposed to Ethyl Gasoline 1927 Number 1929 t-f > Number gf 0 - 0.039 3 11 7 27- 0.04 - 0.079 9 35 7 27- 0.08 - 0.119 6 23 9 35 0.12 - 0.159 3 11 0 0 0.16 - 0.199 1 41 4 0.20 - 0.239 2 81 4 0.24 - 0.279 0.28 - 0.319 0 00 0 0 0 0 - 0.32 - 0.359 0 00 0.36 - 0.399 0 Q0 0 0.40 - 0.439 .0 d 0 0.58 1 40 0.87 1 40 0 ' 1.00 ~ fi" 1 4 4.00 - + fir f i -0- .0- Total 26 100 26 100 Tank wagon Handlers Exposed to Ethyl Gasoline 1927 1929 Number Number i xT fir' 6 25 ft <0- 11 46 u 2 8+ 1 4+ i 1 4+ 0 0 f i fis 0 0 1 4+ Q fi- 0 fi l 4+ 1 4+ l 4+ fi- JT?" 1 .0 -er fi .0 f i fi" fi' 0 1 4+ fi" 0 f i -fi" 6 + CO 2* fi- 24 -10-0---- I1..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. TABLE 5 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. Filling Station Attendants Exposed to Ethyl Gasoline Tank Y.'agon Combined Handlers Filling Station Attenda: Exposed to and Ethyl Gasoline Tank Wagon Handlers 1927 1929 1927 1929 1927 1929 ;-=>ad in Milligrams in 0.280 0.236 0.308 0.402 ingle Sample of Faeces + 0.030 +0.023 +0.025 +0.036 0.294 +0.019 k 0.312 +0.022 ,ead in Milligrams Per 0.118 0.106 0,109 0.142 ram Ash in Faeces + 0.015 +0.009 0.008 0.019 0.114 0.008 0.124 0.011 ,ead in Milligrams Per 0.142 0.111 0.129 0.115 .iter of Urine 0.024 0.025 0.015 0.024 umber of Subjects 26 26 24 24 0.136 0.015 50 0.113 0.017 50 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 manufac turers 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 ! ^ ^ iilfrT^vention of 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 symptoms,-r"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.  . !-2o& *7, 1*Lee-- I -- '',"vUi --._-"jwtr-*--*J^* jij----*J--*j ^^----' ". J The laboratory signs of lead intoxication - valuable but not ' X, specific or final. Lead in excreta lead m blood, blood changes. -- ------------------ ; Typical cases: Observations following immediately after ex- ^-. posure. Delayed observations. tL) 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 u<e quantity of leads present. The extent of the ex posure can be determined if the t^me 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 tnis 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. J \7v ' f V 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. \ ~ / r> / 5. Compensation Cases of Lead Poisoning Proof of exposure in relation to occupation. Duration of disability. Re-empi oyment ( 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 . '\ 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 <d 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. y 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 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 limits of normal physiological states is demonstrated by the susceptibility of infants and children. , ) / ( Experimental ?'ethods , I In a field as many-sl^ded and as replete with pos$ abilities of error as the one under discussion, It Lj pbv'6irs I i ' / -ttsPt the validity of 'Par? /esults\ or conclusions depends/pri- i 1 / \ / 1 marily upon the accuracy and adequacy of methods of procedure. In fact, one of the obstacles to a proper ;\ r of much . of the . -- ve5e/&sbsk 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 ,risk of intro ducing Intrinsically tedious material, it-boeemoo woeooo&i*y -fcn. -set down-dotails ef experimental me thod s<na/ ^ 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. TH-.r03 (Sp.Or. 1.42) and " (i:io) .a .10 c.c. TTs S04 . are added, urCCJU. ijunuAiliiiiitBaa care when dealing with ammoniacal samples. (EaS04 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 temperature controlled by pyrometer so as to exceed CCLuU500 C., the material is cooled, moistened e-arrcefftutl-lWy v;/iith dis tilled water, and treated with 20 c.c. :-'H0a (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, a l t e r n a t e l y , h o t HN03 (1:1) and hot water, the filtrate and washings being caught in a 600 c.c. Pyrex beaker. The filtrate JLa evaporate^ to dryness on a hot plate -- o. a p i V "V.Tc .c. as-k-c , at 105 C.' ~The residue is dissolved in HCl (1:1), is diluted to 300 c.c. and is neutralized by adding 25? PaOE 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. Whatman 40 filter paper and Is washed thoro^ghly^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 the beaker in which it was produced^by means of hot H!T03 (1:1), followed by hot water, the sides of the beaker and the gassing tube being slaidULarly washed. The solution is evaporated to small volume^transferred to a 100 c.c. Pyrex beaker, treated with 1 c.c. Hs S04 (Sp.C-r. 1.G4) and evaporated -to fumes of H-3SO4 After "'cooling ffcH fc ---SSSeiPup--to 30 c.c. of a mixture . V/~^ YS*/ *C. of 10 c.c. 95-;" ethyl alcohol and 20 c.c. 'ater, samd. allowed to^-k!^^. f-'lft*. !.-t-r n ^' stand over night. The precipitate is collected on a 7 cm. & , /} A . -X Hunktell 1-F filter paper, thoroughly washing the beaker anc 4 9 2, ,- , ,/ A Ml o, U^-Ljcz.-ts ai-fkf.-h/0c a4.__ / ^ a^-<K ' ' paper with a solution containing 1 c.c. HsS04 (Sp.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 _____ 3SE3BBX hot ammonium acetate, followed by hot water. (This is SSBt done by first washing the Weaker in which the S'* cT acuZTaXe- precipitate was made, then decanting the solution and wash- t---V S'o.-c. y~i ^ g ^ T.jJT, ings througn ahe filter.) This solution, now diluted to ^fF i- ; * 300 c.c. with cold water, is treated with 2 drops HN0a ,5 . T a ^ Z - i~ y L tsa . (Sn*.Gr. 1.42), and is neutralized by adding 25?? NaGit to o - >;ccv ,0 alkalinity, then HCl (1:2) to a faint pink to Methyl Red (4 drops of a 0.1"? solution of Methyl Red In 50;' ethyl alco-J hol). 1 c.c. HCl (1:2) Is added in excess, the solution is y ^J f cooled, gassed for one hour with HeS and allowed to stand > - Sc- overnight. The precipitate Is filtered off, washed and re- ^ 1' ' Oa.t * dissolved X-\i ( the^same me thodiT^nd"precautions as employed 1/ * ` < at the previous sulphide step. The solution is evaporated - 'S,-" V? .J , to 1 or 2 c.c., and transferred to a 150 c.c. Pyrex beaker, ,-ys, 'tv ' -Ctrv;here it is diluted to 80 c.c. with cold water, neutralized with 25 ? TlaOK (free from iron and aluminium), ; 4 drops of a solution phenolphthalein in 1^ aqueous MaOH, as indicator. 5 drops of 25?? 'laH 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 with c.c. of If KaCr0* solution, the mixture standing on a hot plate for one hour, and at not less than 60C. overnight. The precipitate Is collected on a 7 cm. Hunktell $1-F paper, the beaker and paper being washed thorough^>ir 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, Aa/V]j y***** tP 5 c.c. cold HC1 (1:S) followed immediately by cold ! Zj *XJU. v/ater. The beaker and stirring rod are washed and^ decanted through the paper. In a similar flask a standard is prepared containing sufficient XeCrgO^ solution to be equivalent to 0.30 mgs. lead, precipitated as PbCrO*. 100 c.c. water and 5o 2 c.c. cold HC1 (1:3") are added. To the sample and to the standard, 2 c.c. of a l 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 colori meter. , l'C.C XL -r (2) ' rf-y -<--fa..<i.i, _ c K s- . Analysis yCQ' -X. cu-sx of Faeces .x., . ^ a ...;. . & , ' - r ~ A o c_<t <-tc -- V .V .C ..-- 'Li-,i f '~r^<2, a. S '.o -& "C-+" c< '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 g q ^ ^ a electrical muffle furnace at a temperature controlled by pyro- meter so as not to exceed 500 C. After cooling and weighing C?dVLXjiX, the ash, distilled water is added wi*ffiebe and the moistened^ 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 ini0o (1:1) and hot water, and discarded. The combined filtrate and washings J> U J -'<1 dL. C u - i c - L . 2 - S c c . are evaporated to dryness on a hot plate# ^he residue is am* cu.J. . dissolved in HCl (1:1), is diluted to approximately 300 c.c. tat 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) r> 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 KaS water to which has been added 0.1;' . 's of its volume of HCl. 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 HaS has been driven off," whereupon it i3 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 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 mason jars. Except for those large amounts of cal cium or fat, the general procedure, after weighing, is to in troduce suitable quantities into 600 c.c. fyrex beakers to gether with 10 to 20 c.c. concentrated H!los , V c.c. concentrated HCl, and 5 to 10 c.c. concentrated HaS0*, taking down to a char on a hot plate. The char is destroyed by freouent additions of small amounts of concentrated IrII08 . Near the end of the pro cess 2 c.c. 60^ perchloric acid are added, while additional amounts ot KN0 3 are introduced until no char appears on evapora tion to EgSO* fumes. The material is evaporated to small volume, ~f 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. No HaS0* is used in the digestion of bone or of tis sues which cou s i n bone. Such materials are treated, with suffi cient HiIOa (1:3) to complete digestion, after which the sample i3 evaporated to dryness on a hot plate at approximately 110 C. The residue-is taken up in 50 c.c. concentrated l!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 HNOa , and set on a hot plate until dissolved. The residue is fil tered off and washed alternately with hot IIN03 (1:1) and hot water.^ The filtrate is evaporated to dryness. The residue is dissolved in concentrated HC1, is again subjected to evap oration to dryness and is finally taken up in a minimal quan s- Qu) . tity of 'v*r[ltV?rr|,<r.aafcari HCl. Upon being diluted with water to approximately 300 c.c., the usual analysis is carried out. Fatty materials are dealt with mlIU' *- .i~*^j/ by heating with concentrated HaS0* to an incipient char, after which they are treated with successive small portions of concentrated HNOa 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 KN08 and 60*' perchloric acid. This entire procedure is accomplished with mmk. speed and convenience if the sample is divided into small quantities in Kjeldahl flasks. Constant attention is required. ) / hemarks on Analytical Methods. A survey of analytical methods 1n vf/ 1924, resulted in our use of those developed by Fairhali , with certain modifications instituted by " oh'-m Edgar. Fur ther efforts to shorten the method and to reduce the slight losses of lead to the minimum, d t a w resulted in investigation of technical procedures originating in the minds of the lab oratory staff, or suggested by the work of Avery, Hemingway, Anderson and Read , Taylor , Franci.s^Vt eand his associates, and Tannahilf^. The preparation of O B samples for analysis by primary ashing at low temperatures (500 C.)t aban- coned in favor of initial wet digestion methods except in the case of faecal samples. Furthermore it 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 Taylor- , though we have not investigated the latter method. The sulphate step, after J-/ . . the manner of Avery at nl.f has been found t8 frto necessary "T3 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 v/e havk been loathe to eliminate it . / in favor of a thiosulphate titration, sulphide precipitation, or the acid sulphite method of Ivanov . The thiosulphate l-J titration method r :-. . tfxruom consideration.,-- is--us* judgment, in ^ amounts as low as a few hundredths of a milligram'-- .ii.The fa^t^ttiwhfacr|tTtthhe carbazide reaction flgymnna L, . upon chromate(instead of lead becomes of mimr significance oh i.cctr+ -i * o .J .vhen that the QsapdsO elimination of soluble chromate may, be . _ _ _..____ . , . .1 fcj1. 1II..I iTlftTaa by tfeet t-Si./*vKiX--I ^ i lU-tMXC--`m care^required 'to ovolo the inclusion of non-lead materi- j, A als in the other two colorimetric reactions. An advantage in the use of S*diphe;nyl carbazide is found in the identical \ quality of the colors produced In the standard and the sample, a.jnaJ^ter-rffFSTSr'-a-ccom pjJ-^ed_Jji-co^rJLm a-trl^^om par 1 son i^ ' 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- Dlored, they do not Influence the validity of results, wirixh oftu ld nat, have..hern a 'u h fcm n n A Vi a p r j t | r [ r>T> accurate pyo^ ^Hyea otatriiwod with-lose- aenyi teive- gethtiriaj on / t h w n n a.attM iLU .Pfl.h iii- uii the uthi`. . >'t>\J j --- ------ ---- " defi nite advantages have accrued from the accumulation of comparable ) data over a period of years. Tha.,gradual modification-,of__ _ / methods oiL-the--b&sl a o f - W B g i asj red "facts, 'while maintaining technical- uniformity- otherwl?,g , h an -yiBTdH'"a body of. increasingly conclusive inforpaila* -Ha-1eraTs~~and Technique a 01499 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 slight1 as compared to those associated S V tj i . ^ ^ Ivc) with the collection of samples.of any hind- Lt_is_jaecossary to AA4*i/***-t+A+K y \ ( Zv , ** t j L c - n l j M - C 9 ^ J . * I- . *~ 9" * , \ J- P n -J 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 MilUJ essential to *aee 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 --W*/ ,,t\W*.Vi>*** The lapgoefe-poytien of our samples have been collected in glass capped preserve jars, and In gallon jug3 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 'veil as cleaning reagents may contain appreciable quantities of lead. Special care :1s 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 CIchrornate is used as the cleaning solution, in order to avoid the contamination of lead found'frequently mrr'di)"`M i iife*-ti1-fr in the o-ttAi commercial it64e*4*e. 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 r i) analysts for lead carried out. 1,'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- s 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 5amount 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 M l H 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 ftwuuring a ourselves the amounts of lead which nay be contained in the maximal amounts of all the reagents employed in a single analy sis, -hi la 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. Bj 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 a < continual check on materials, equipment and technique, it has been possi L. < J ble to s o s a r against high results. Slight loss of lead is unavoidable harnnse of fcfoa flolubll'ifry.ofi.lead compounds ,vk^-c^r nsnnll^ piqy b n . n . ^ -- -5.T1nr.i ji9> results, there- orej . , err on the low side. The extent of such errors is indicated. hj a typical experiment designed to tost- the analytical procedures orjly> i.o. In the absence of organic materials. Lead-free control samples containing 2.5 grams CaClP , 4 grams ;;a3?0^ .la'd^o, 10 c.c. HC1 (Sp. Or. 1.10) in about 300 c.c. distilled water,.,|gwere treated with variable quantities of lead unknown to the analytical staff. 'The results ire shown in Table I. 01 r p. w O jfL. Table I i . .<` ir , * `s . , ' /, `s 3-f.. if\ Milligrams Milligrams Lead Added Lead Found Nil Nil Nil Nil 0.07 0.07 0.07 0.07 Nil Nil Nil Nil 0.05 0.04 0.04 0.04 Milligrams Milligrams Lead Added 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 j 0.16 7 0.19 3. "ethods of Estimating Basophilic Stippling of the Erythrocytes. 1 k K . n3N i. f* t ?sc.s. s The changes character n=ts erythroc.y tgB"uf the blood--- in notation to X1' the absorption of lead compounds, gpHBar a specific impor- tance to miroscopic examinatlons/of the blood in cllni-A^ ' - cal or experimental work whlch/^oncerns itself with lead. -5 & r> ^ Without preconception as to the relative merit of the methods'll ........X ./ . . ...... ;h 6: of detecting variation-^ in/the content or distribution of I basophilic material in i;ed blood corpuscles, we have elected. f - k | to make observations oft theVoccurrence of stippling in blood smears unmodified b y fixationY haemolysis or by vital s t a i n s . v -- \ vp"- ^ i The adoption of tfiia as a generkl procedure on all cases, *~ . *t t even where in ,srorae instancs addi\lonal methods were em- /' ployed, was based/on the impossibility of sampling by any / PHS* pJ! other mean's than that of a dried smeap, under certain condi- _k t s tions of our work. Thus we have attempted to obtain a satis^5" ^ &^ factory degree of quantitative accuracy in a simple method F .applicable to any subject at any distance from laboratory S>-^ fc l ? facilities. '* ^ Several Jnmear3 are made from the blood of each 1 n ,1 st(J /ahJ*~ 0-CUx) *-- "fa j^qt saw x n iffl1fftnn rMrlm^pr md~-*i,f^nnf>Br n > Ul L"^ *-- -4i -UH ~U'*-v '& 1 n f > a TVTT^Vlinr./.yt-fl|Q n c ,.la-pftftd hi ft , r>n r h ftgjt / flIT g-fl.l sub-5- -f n! p5 ^. __ ' {, elides. The slides are perm.-1ted to dry naturally. are * n-- ! , labeled with the subject's name or number and the date^ They \~^ * j / m a y 'Ka Qv n '** 'V 'xi i f Inn 1 h m n n f t m i y rtf' rmftft fl.r P-gAri-W n h V q 1 P ftf* Jj M t, b 4 t ^ j . ^ 4 x L ^ j j y * * . _ _ _ s, ( - x .j p ) *;*- t i w ithout aiiyaemonstramg ch!mgi5h",,TT''Th83'~,'irilu hepL Ji y u.id...clean. -- -r-^ QjJtxJSrz}--) At smtA*& phey are inspected^'and the best and roost uniform one3 are selected for staining. The stain employed is made up of 1.5 grams /ethylene ^lue, 0.2 c.c. of 1".. f?aOH in /ethyl /lcohol, in 100 c.c. 'ethyl Alcohol. The smears are immersed in the stain for four seconds, washed rapidly with 0.025;' aqueous TIaHCOg solution, and dried r rapidly juaafiMNBHQ in 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 T m -- i BwAIitr1m 'frrprrl ~nrr . careful techniqueand micro scope lenses capable of excellent definition are required to obtain good results. It -ie- dooirable- to-1wtaiBine ^ h e smears cua) in a strong light, ^.vith a magnification of noteless than 900 diameters. di'l'.vJT e x fiv fJLu-ld-s--gor'p Km*S , -,<4.4 i A diX--. FZifj, <* " -Tn nir^-^^frryrl nnaa i ^ fr* nffinH.. n fn 'n . B A r * v n h i n r > the central portions of a great many more fields. &***-y' Vn nhoianvatlnna in which the n^mr mini1n11 nplv -y-- J : I\pm^n l-> employed. Caye fvri selection of fields of most nearly uniform distribution of erythrocytes reduces the variation in the | [ ^ i 01 505 number per field. Ilovorthelcss congiderabl c. aviation in -tfaiy far tor -acauTt The number ^per field averages approximately 250; -in i msiiinr nhSTVofrions. Star fifty fields m m ], Ijlluu t"rtijii > i-- * approx- imately 12,500 erythrocytes. ^ ^ .. ; ru<jjLj tvo %, *4** 3*4^ S<*i*wse appreecciiaattiioonn--of the limits of quantitative accuracy ., -- ? obtainable, in view o f t h e opportunities for variation in tech nique m the hands of a single careful worxer, may oe had xrom 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 cpmpaiyison of these two sets of results f i ~ * a n the variability which may arise from the preparation of smears, plus the microscopic technique.-- wiri etrtrsarc there io a foil* dcfer^"'flT"'aceursFgy~Tn~ fh yrnaAdiifj -, Tfl fh n I.j \ finT ft =ta s5f",|ihe data which 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 8 01 50>6 >f; qint"* arT' excellence of clinical observa tions is dependent upon the sJcill, care, and judgment of the observer rather than uton specific methods.. Thu a,-- -it <a afts-rraiy pprf itn-H- to descpihr prrrmdnrre. .u. is nf_.sr.yne. paint IL-ut -the essential purpnnr.v ^ -YtwcvW ^ -- - Table II -y / r--u.ui\ , // * .. 2 t o * r v M o i i _ o n Ten Successive Smears made from Same Subject* 1 2 3 4 5 6 7 8 / /9 / 10 Average subject B. Subject J . Subject N.S. - / 5 11 9 7 11 7 9 14 7 5 8.5 19 26 17 26 19 22 24 21 31 13 2 1 .8 141 145 180 135 163 165 138 169 150 131 151.7 Table UL ?vrif,1-Oft 'i/i., 'I-:-f- t'H/h _- '. . H .-0 A/ 4x1 <^*A*U-J& <Hjl U*j~fum fi*a.<n*o^ XvLi *-j UxierwJ L*# +4 * ofijservStloj^] on iPtfoj SmeaVs ^-~' Ob.apvfltloria qn ^SJngj^ Saaai; / , ly'rfrQgrSaae^Sub j W '- <**'-/&*&iAiAfijrVd+aUrf^i by D. by S. ' ^.ai/.vrv?.#*. iiy~?f)ey ,iiuv>-**^*^7^*4^ by D. by S. 1 2 3 4 5' . 6 7 8 9 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 97 106 92 85 110 106 98.7 y 5?/ t&i CM^M^Zr^c) Aa^ um^J "th fihcfcZZ <^~'zd. ^1. G MiX<ga3r;auestlonlng of every subject was required, in order, to .etermine the occurrence, duration and slgnlfi- SliAt . cance of^exposure to lead compounds. So many trades involve some contact with lead that eareftal rerublrry-u/ the entire 'ii*Ji& a t~~s occupational history miat. be mode matter. Z % jo tZ e L jL 4 l/ W E a to 3>ea4..aoaaaaaasa^t UMa jJ t -lt o&AM JLk W &L - :> > MTV*44A^ ' v/as desirable to "Zi"-t^c. KC<4 tr individuals who exhibited evidences of chronic or acute disease which might interfere with normal absorption, metabolism and excretion. L-u-^i / J 3< lv*^"tsL *f effort wao aado- to defect) < \ _ OYldnnr**0 of> wy-LM.anri, {^fua+ZL+XX _ attention was given to the discovery of abnormalities associated with lead intoxication. 7 4 ~ Jo t ttje sake of spns of various groups of subjects, information a quantitative character/ / was obtained go far as josslble# ^ jj^y^Lo-t1&erh y d.ata. and of A3 ~ther ma^steeirs .ame.nable..J;o^ ma-thona-tolcal treat m en t , h i'i'rn hrmn mrvlnrt m it 1"r T '-r*'girl iv pr^ffadirr". < A-\- , -- SA-''-- v.<fl.jj-S''* ' i, + / s/ o ,* C*'iZ/& ; ..r - .- l (' f , 'J+XS -**.v/ . ->T> Y` ' d,,<r.t-* ? 1 / \ 1/ Bibliography (rHupfron -*t ) 1/ y v Fairhall, L. T.: Load Studies. I.The Estimation of Minute Amounts of Lead in biological Material, J. Ind. Hyg. 4; 9, (1922) " 2/ . v Avery, D . , Hemingway, A. J., Anderson, V. G., and Head, T. L A.: Determination of Minute Amounts of Lead in Water, ' with iotes on Certain Causes of i-rror, Proc. Australian Inst. Mining and Metallurgy,^43, (1921). 3 cilJyi: "^Taylor, H. B.: The Determination of Minute Quantities of >L Metals in Biological Material. Part 1., J. Proc. Roy. Soc. New South V/ales, 61: 315, (1927). ' Francis, A. G., Harvey, C. 0., and Buchan, J. L.: The Determination of Small Quantities of Lead, with Special^ _ Reference to Urine and biological Materials; Analyst, S V J7 ** &y December, 1929. ,^vTannahill, H. W.: A Critical Survey of the Methods for the X Determination- of Lead In Biological Material. Med. Jour. ' Australia 1: 194, (1929). - /y ./Fairhall, L. T.:. Lead Studies XI. A Rapid Method of Analyz' " ing Urine for Lead: J.Blol. Chom. 6C): 485 (1924). 7/ <. . -- It'l'- , , ivanov, V. N.: A Sensitive Reaction Jof Lead. Chem. Zeit. 38: , 'J 01510