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Table of Contents y, \ *h;'' ` ~:^iV ''' ' \ " r-*** .- A* y**_fV>*V" * " r Ar 1` ' Preface . Chapter I Introduction Chapter II f\'T?* "_ . ' *\\\ Methods cv w Chapter III The Sources of Lead Absorption in the Modern Community Chapter IV The Absorption and Excretion of Lead in Primitive Life Chapter V The Magnitude of Clinically Significant Exposure to Lead Compounds Lead Absorption and Lead Excretion in the Lead Trades Chapter VI An A ^ r a i s a l of the Lead Hazards associated with, the Distribution and Use of Gasoline containing Tetraethyl Lead Chapter VII Certain Considerations in the Prevention Diagnosis and Treatment of Lead Poisoning index 0014429 Chapter I Introducti on The usefulness of lead and its compounds in many fields of human activity has gi^en them a unique place among the materials and products 1 of -early arts and crafts and of modern industry. Thus ample oppor tunity has "been afforded for the demonstration of their poisonous proper ties, The insidiousness in the development of lead poisoning the appar ent capriciousness of its occurrence and the variety of its clinical forms have joined to the curiosity of investigators, and to stimu late their efforts in the interpretation and the mitigation of this occupational menace. And yet a degree of vagueness as to the physiolog ical activities of lead compounds maintains a lively interest in the subject* this "being heightened by the fact that whereas the means of prevention of poisoning have steadily improved* new uses for lead-hearing materials have developed at a more rapid pace* involving'an flasatr increas ing number of occupations and persons in the hazards of lead exposure. Indeed, the number of generally distributed commodities which contain lead has become so great that some degree of lead expos ure has been carried into the everyday life of all persons. The investigations which are the subject of this volume derive their importance chiefly from the fact that 0014430 they tfon?tltu-fro source of Information as to the mag nitude of the lead exposure intrinsic in modern life. They began in 1924 when it became apparent that the previously limited distribution of gasoline containing tetraethyl lead might develop into a commercial activity of very wide propor tions. The experience of those who had developed and dis pensed this fuel up to that time indicated that there was no acute or immediate danger but the possibility existed that prolonged exposure to small amounts of lead under the .wwwurrrrn conditions arising from the distribution and use of the com modity, might cause a significant accumulation of lead in the tissues of many persons in the industry and in the community at large. It is not my purpose, here, to discuss all the work which has been carried out in this laboratory or elsewhere, in the study of this hygienic problem. Much of the information bearing on the subject is readily available to those who are interested. However, one phase of our.work ha3 resulted in the discovery of facts which are of such significance ,as to justify their detailed presentation both In relation to the original question at issue, and to the larger problem into which it has come to be merged. Periodic Investigations have been made to determine the extent of the lead exposure associated with leaded gaso line, by the careful study of selected groups of persons who have experienced the longest and most severe.exposure to the vV conditions established by its use. Kehoe and Edgarv carried out the first observations of this type In 1924-25. Late In , .3/ 1925, J. P. Leake^ and his associates in the United States Public Health Service, following a program outlined by a commito|&fjiuJ teeA appointed by the Surgeon General, investigated the matter further and extended the number and type of subjects observed. This laboratory VK5 made three further studies, in the winter months of 1926-2?''/, 1927-28^^ and 1929-30 respectively, the first two having been made the subject of detailed reports to the United States Public Health Service, and to the^inaustry in- volved. Hone of the data have been put into such form as to be generally available. The primary purpose of these investigations could not be served rfry by attempting to detect evidences of lead in toxication in exposed persons. Kather, it seemed imperative to anticiippaate sucnh adeveeiloopprmaeenntts boy adetermin ing whether ' :7w h Ich ,might eventuallyr^lnduce lead intoxication. , . *,.____ ______ ..... .. __ _ ... . .^ . J* rutiMd jLtJi , $0 dsJlj & ' '" ` l:'? < *aar- c ons tar tar c1a^ibhship-UalTBeieir thp rate of sxone ion, or. beUMen th amuenrb' in-the tioouea an the rnfaiDif mrrrntlnn -en^lytlrnl flftflftfrYat ilrun on 1th-n 7 blooti-wi ^ h tr lndluatg"xne Quantity of absorbed11*3Hrtd. -might be-- that some gw i-wVWTffiSrCHd `BBritepr -e w ep tiblo of ollnl -eal observation be found to vary with the magnitude of lead absorption, as for example, the microscopic changes in the X-* blood. Lacking information on these points y& W ,-,A s f noooastrry to combine clinical M L / wjjfea*faeaga3wirtlw uf a n a l y . aried groups of subjects with, known and unknown exposure o lead compounds. In short, nothing less than a comprehen- sive examination of the physiological of lead compounds iaritaad9S8&3gESS$ came to be the subject of investigation. 7 & _ several years 25f e ' have been devoted to such ef forts/ j .;i demonstrated that the normal individual in the United States, experiencing no industrial exposure to lead compounds, Is excreta^- measurable quantities of lead in both the faeces and.urine. The first observations indicative of this were reported by Kehoe, Edgar, Thamann and SandersY The facts as to faecal ex cretion were 3/ verified by L e a k ^ and his associates shortly afterward. They have been established by the extension of our observations to several groups of A" carefully selected normal subjects,. Francis and his associ V Mote co ates, as well as Millet, have eataoXYahed the existence of a similar 's4tuoon in England. nmi...|TTimtpa..nf vl* ***-< o Eadham and T a y l o r ^ Cooksey and W a l t o n ^ and T a n n a h i l l ^ ^ o have obtained like results in Australia, while Fretwurst and Eertz^/ have reported similar findings in Germany. VJe^M as well as o t hers^, have shown, further, that the rate of lead excretion in faeces and urine varies with the magnitude of lead exposure to such a degree as to differentiate' groups of workers in the lead trades from each other and from the non- industrlallzed population. These facts have led to the fur ther investigation of the conditions of exposure to lead "both in the lead trades and in the community at large. With out / v - h g n >aray_-,ygy fVom the importance of the original problem, the study of the lead absorption of the general popu lation has claimed an increasing amount of attention. This has become the more necessary since those persons who have . had the most severe and prolonged exposure to the hazards of leaded gasoline^fail fiB5ptoBfcS35r to differentiate themselves from unexposed persons, on the basis of their lead excretion or any other factor. Whether this is due to the limitations of the,methods of observation or whether it is the result of a n i n s i g n i f i c a n t magnitude of the leaded-gasoline factor in the total picture, can be determined satisfactorily only by the of the several sources which contribute to the absorption of lead by the average normal man. By the same process one may hope to obtain some evidence as to whether such lead absorption is now or is like ly to become significant in relation to the public health. Thus a number of problems have presented themselves, as the direct outgrowth of what may appear to have been a simple experimental study. Certain specific questions may be formulated as matters t , as follows: 1. What are the sources of the lead absorbed by the average normal man in the m o d e m American community? US 0014434 '.m J -iuCi. J^kv -&.s^ aJr**%fZe*' . 3* Are. th e;yt> the result of modern industry and ,<.; Jt *s commerce, or agaecsfchey f r f i u x ^ U F ^ ^ r f - y 7 * . r ^ k L a 3 condi tion^ of life on a lead-bearing planet, or are both factors active? f. Are there evidences of an increase in lead ex posure as a consequence of the distribution of leaded gaso line, or of any other commodity or factor of modern origin? S' 'si- r j ahirfi. tJ. AS0': OOKtHL4JOT- The methods which have been muyltvycil v and-- feho r e sults which have been obtained in answer to these questions, are dealt with In the chapters which follov/. T&lJ nJ*J *j -t j s > v-jf ^ -J.i ^ t k P cj,\i n<2Zj f~ Jl iix^ f ^ Adatu*Lj, *{ -tri tjJ t-'i ff H^d****** CXxjju^iX-\J 'jJvcvJ '-/u Cld CL^'^` flL' ' *4`"/') -yy&ILkt rifa*. ** Js*Jl ^ ~V y , ^ f ~t Bibliography Kehoe, Robert A, and Edgar, Graham; A Study of the Hazards Associated with the Sale and Distribution of Ethyl Gaso line. Printed report to United States Public Health Ser vice and Ethyl Gasoline Corporation, June 1925. 2/ cake, J. P. and others; The Use of Tetraethyl Lead Gasoline ~ in its Relation to Public Health. U.S. Public Health Bulletin Ho. 163, 1926. y Kehoe, Robert A. and others: A Study of the Health Hazards Associated with the Distribution and Use of Ethyl Gasoline. Printed Report to United States Public Health Service and Ethyl Gasoline Corporation, May 1927. Bibliography (cont) 4. Kehoe, Robert A. and others* A Study of the Health Hazards Associated with the Distribution and Use of Ethyl Gaso line. Printed report to United States Public Health Service and Ethyl Gasoline Corporation, April 1928. 5 Kehoe, Robert A.* Edgar, Graham* Thamann, Frederick; and Sanders, Lester: The Excretion of Lead by Normal Per sons* J. Am. Med. Assn., 87: 2081, (1926) ' 6 > Francis, A. G., Harvey, C. O . , and Buchan, J. L.: The Determination of Small Quantities of Lead, with Special Reference to Urine and Biological Materials. Analyst, December 1929. ,' 7 tl Lt d. ui Millet, Horace:^yJ. Biol. Chem., 85:265, (1929) 7 2-S^ ' ' 8 Badham, Charles* and Taylor, H. B.; Studies in Industrial ny giene, N0 . 7 , Lead Poisoning, Report of Director Gen eral of Public Health* New South Wales^for year 1925, Sydney, (1927). 9 Cooksey, T . , and Walton, S. G . : Electrolytic Determination of Lead in Urine, Analyst, .February 1929. 10 Tannahill, R. W.,: The Excretion of Lead by Mine Workers at Broken Hill. Med. Jour. Australia 1; 201, (1929). 11 Fretwurst, Fritz j and Hertz., A-rt u Quantitative Deter- . mination of LShd in Faeces and Urine and Its Signifi cance in Making a Diagnosis of Lead Poisoning, ArchJ,Hyg., 104: 15, (1930). J AA k 2 - & r* \ l c4- 1 ^J**-^*^ ^^ $$ U t y w U F, ,Sf. , ` - SZllk. Uj a ^ . +J) jfc; ' -TLfji Kehoe, Robert A., and Thamann, Frederick; The Excretion of Lead, J. Am. Med. Assn. 92* 1418, (1929). Leake, J. P. and others: Loc. tit. Badham, Charles, and Taylor, H. B.: Loc. tit. Taylor, H. B.; The Determination of Minute Quantities of Metals in Biological Material Part 1; J. Froc. Roy. Soc. New South Wales, 61: 315 (1927). ) Francis, A. G..pinaT"Report of Dept.- : ' Com. on Ethyl Petrol, Ministry of Health, Great Britain. (1930) Tannahill, R. W. Loc. tit. '/ Chapter IV The Absorption and Excretion of Lead in Primitive Life No Information available as to the natural presence of 1/ lead in human tissues. Nor m * It possible to determine whether or not some quantity of lead Is to be regarded as a normal consti- V tuent of the animal organism if observations confined to in- dustrlallzed parts of the earth. On the other hand, it would' seeing that there should be places that have escaped the commercial devel- y/ opments of present day civilization, m l Xft/which the opportunities v for lead absorption -are-of the same type as those of primitive men. A cursory examination of localities which offered some chance for the existence of such conditions, led to the consideration of Mexico as a field for experimentation. Certain requirements were set up as .the basis for the selection of specific communities, as follows: LX (1) 'Tfhe conditions of life must be such as to exclude the possibility of occupational exposure to lead compounds at,any time; c y ($0 -'ilhere must be complete freedom from such opportunity for lead absorption as would come from the use of lead paints on the outside or inside of dwellings, or on objects of general us1a<au. C&feMcic9- ,ft , ' >UA& of canned goods, metal containers and cooking utensils, piped water supplies, and machinery of any - k i n d w e a K w t W ' i U - feanded-- as adejcptafre*"b9rSfi'3``'TcF,'*'1lih^ (S) proximity to cities, or easy transportation facilities to and from highly organized communities constituted a further objection} r {^) gaining and smelting activities, with special reference to lead- containing ores, must not be carried on within such a distance as might provide opportunity for contamination of vegetation, surface soil or water supply; ^Ja^employment of firearms, and the Inclusion in the diet of game obtained through the use of firearms to any considerable extent, was accepted- qa..reason for exclusion; be a considerable number of people available for study, and willing to provide samples of blood and excreta, as well as articles of food and objects of general use. o -vw\hhj^ C-Y y Persons who--ane familiar with Mexico^ eeene--will / recognize how easily many parts of that amazing country meet these / ! requirements,, but-H ^ r e " ^ ^ x a c l w g ' ,"s^r td"--arou9e con side rable'^dbi^^^as'^t"o'`'th^fr'^ffOQ:p-lrete~fui`fl'ilic.ent . (Hi <Uk jut]#//fd/ -Hju Ivrdf, t Through the generous assistance of colleagues in the Department of , Public Health of Mexico, It was possible to establish the probable suitability of several small communities within comparatively short distances of Mexico City, and after detailed examinatio n -e~ several S1\i ^i such villages and ^afterj establishing mutually friendly relationships with the native Mexicans, our doubts were dispelled* aw#"Ex perimental work was undertaken in two pueblos, since any conclusions as to the natural occurrence of lead in human beings must depend wholly upon the absence of artificial opportunities for lead exposure, soma description of these two villages and of life within them is necessary. _____ _ ^ ----- <je caChi a small village of about one hundred milles, situated on the Mexican plateau, thirty-one kilometers northwest of Toluca, in the State of Mexico, At first sight, the vast expanse of level plain in the region appeared as though uninhabited^ There were no towns:'with' obvious highways leading to them, or.,.with the { : smoke of factories hanging over them, only evidence of human existence in the immediate vicinity was furnished by occasional flocks '.of cattle, turkeys and chickens foraging under the care of children* V ^ / s T l h e adobe houses e-d2ashi were ecmple-te1y ^ b g c t rr ed" by'TTOTTT'grfflb'ff't -x_eady~-fo-r--th e -h a r v e s t , so ,.,that-- o n ly H ^ s t a n d ih g ^ o h ' a ^ h ^ b b k " 'ODu ltb -th rr ~Xe^ox..^.ap]^ar^Lxooa^be^eeen scattered, at irregular intervals in the . c^'Vk,, } j, iituV tdUlL midst of th ostmtuttmel field of -gasai. From- such a vantage point ane"~H could see the church tower and the-tile-roofs:of- Ixtlahuaca to the^bast, .... and at a distance of about five, kilometers, while to the north"the small town__.of,,J_o.c.o.titlan--was~just-recognizable as a series of-white and red specks, d . To-- the-- south r a n d within two-kilometers w e r e the white chapel' and'the rambling walls of-a e-eaewhat dilapidated hacienda. AVithin -the cornfields of-the village one came upon a tortuous ditch*._in...which,a.plentiful supply of turbid water was flowing, since it was..ihe rainy "season. . A~well -worn-path-foil owed...the....small-- canal-and.,,led to the houses..fc.,,?.lXr..o.f,,..yihi.cli,.,,yrexe situated .so as- to be- conveni entl'y sup- jgJJ^d^i-hh^Vater for washing clothing, and for every purpose except that of drinking. The latter was furnished by a deep well over which was an adobe building roofed with tile. A rope, tied to an earthenware vessel, ot> provided the means of drawing the water. So-th--men-and-women,,w.oxked_.in,,. co the -f-ields"but ''sdme,'''d'f'''the---women...,,w.er.e,,.j;.o..be seen, washing-clothing.,,or 7/QQl___iii-the stream,--cai'<iing-wool,-spinning...thread on crude s p m c H e s * or~"* ~7f/o weaving cloth on simple.looms tied to the rooi-tree-of the nouse. -ttmall-- XUx '-..ehildren ,,numerous.d.og s , and -an occasicnal_,,amall-.pig by-1hg-hind lsg_fr..Q,,. ocpupi eel-- t h e d orryar d . TJie-- sngl e-r oom"hou3'es~buiTt-- 1 -? "*-a **w , o of-adobe-'blocks, with one door and perhaps another opening for light* TU* pegs on the w a l l y These took the place of tables chairs andheds. A simple stone hearth without a chimney was in one end, the smoke finding its way out under the open eaves. Several earthenware vessels of variable size, a three-legged flat-topped stone and stone roller for grinding corn, a flat earthenware platter, and a wooden ladle constituted the .csi*ea& culinary equipment. . ~ The occupation of the men was purely agricultural and pastoral. The only metal implements found in the entire pueblo consisted of sickles and machetes* these.,-1att-er^serving--the^pjeaaefn]-- pur.pLO.se^-- .of~.husbandry. There was no game and no hunting, furthermore, the innabitants had no firearms. No pottery was made here, nor was there any manufacturing activity of any kind in the two neighboring towns which provided the only convenient trading and social contacts with other native groups. Uachi was poor. Its people had poor clothing and few belong ings. Nevertheless it was essentially self-sufficient. The people ' / >'/ produced their own food out- of their-own soil. They had corn, beans, small quantities of barley and wheat, and numerous other vegetable pro ducts, together with milk, eggs, pork and fowl. They were well fed, and in general they were healthy. Tne altitude of over eight thousand ieet provides freedom from excessive heat and tropical insects, but the warm bright days permitted tne growth of vegetation the year rcund. Thus there was no hunger. Such food as was not required in the village was sold or bartered for nine, cloth, pottery, mats, sombreros, Berapes, and rebosos. In general, however, very little was produced in excess. Thus only necessities were procurable, and though tobacco relished greatly its use was infrequent. Pulque, the fermented Land commonly pu-tJ&efiecLj juice oi tne almost ubiquitous magey, was easily available, and was generally used as a beverage by tne men and b o y s . Tnere were no highways between Cachi ana the towns in the vicin ity. ln-acm-#__tinere were_...no-:-reu:Qffni-zabl-e--r^-aa-B^-i-nto~-lxtxahuaca. ITT1was-* u sually necessary to walk or to ride on a burro or horse to reach-it. a.ur.nwfihiifi rids M.fT*q aa _t.Via-- si-- ^wtTTonabl e outBbme-, \\tuctaT.-^l-o3ree^t^:ixtfafruaea7"^hc--onlrir-'phy-B14iian_on-- t&e--'vclTilTy'i"',~gsvftetery"as'si itan ce lanTTlih"'seyer'al" o o c a ^ on s ' drove us to Cacni *,,showing an.-astoni shing skill in- going-- aro und , over and through pools of water ana mud . m .the open plain, ihe-- gr-ea-ter-numberof nis medical visits,.joiifcaide-Ixt 1atttracca~ar'e~na'de~~on norsebablc. --Thr ough the greater part of the year the automob is,,a.-mark~Qf-- distin'bti'oh, rather than an article....of...utility. - The Indians walked or trotted, often carrying-a-load.0 1-.sticks or otuer material-several' times 'their own'buix* `Ta.e_jo.iiiy- n o r a s i n tne village. .was....tne. property,. pi,, the-cniei. V f ihe visits ui the Indians to tne1"neighh&K-iag towns were limited to market day, ana local or general fiesta days./ The-- foraer, whidti occurred on.ee..a. week,-- provided" an.opportunity--for-seeing.-and...perhaps . purchasing-or-trading for articles frora the city* in Ixtlahuaca merchants irom_...Toluca.spread their wares in open- booths along the- streets, while people.from the countryside pilea tneir products around tnem on the ground and offered them for sale or,.*trade. H w e v e r , - t h e pervading atmos phere was not tnat oi a market place "but rather that of a gay "bazaar. The social life of the neighborhood found its chief expression in these weekly gatherings, if something could be bought or sold a pretext was. thus provided- for a day.of visiting and pleasure, m whj.cn commercial__ ... matters were mere incidents, 'vtT More distant places were visited rarely. Only one of the persons used as subjects m Cachi, an vld man of seventy, had ever been in Mexico uity. ne nad traveled the entire distance on foot, duri-ng-the-^oiobraifion ~o-f-- th e-.fies ta--o f-- tn e--vdrg-ii-ofuaud ilupe, The Hancheria el Colera is a small pueblo near Capulbuac about twenty-four kilometers southeast of Toluca and approximately fifty kilo meters from Cachi. Its people and its community life were so similar to those of the village previously described that no points of signifi cant differentiation were evident except that the variety of food mater ials generally used was somewhat greater than that of the people of Cachi. This will be shown in the list of food san pies on which analytical results have been obtained. No mining or smelting of lead has been carried on in the State of Mexico according to information supplied by the federal Institute of Geology. No deposits of lead ores were known to exist in the vicinity * of the two villages in which observations were made though three obsolete documents granting claims for the extraction of argentiferous galena in the town lands of Aquipan, in the extreme south of the state, were found in the Department of Mines. The fate of these attempted mining develop ments is not recorded. Kf 0014442 n servation of the activities of the people In the two communities led to the recognition of only one opportunity for the artificial introduction of lead into their food. This came from their use of earthenware utensils, which will be shown to have been glazed with a lead compound. Considering the antiquit,v of pottery and lead glazing materials, this may not be regarded as a modern phenomenon. Some idea of its significance as an early example of the use of lead-contain ing commodities may be obtained from the data of this study. Vv Fifty-three subjects in Cachl, and forty-two in Colero were selected for study. Each subject was questioned as to his birthplace, age, occupation, visits away, from the village, and illnesses, a cursory physical examination was made for the purpose of eliminating such as were ill, and a determination of the haemoglobin of the blood by Fare's Instrument, a urinalysis, ~ i> <9 and blood smears, were made on each subject. Fifty cubic centi meter samples of blood for analysis were obtained from thirty- four subjects in Cachl. In the collection of these samples care was taken to avoid any contamination. The syringe and needles were sterilized in a small metal receptacle heated by an alcohol lamp. Distilled water had been carried along for 5> Mj. o*& <*** , the purpose. After fe&aAnin-g. each sample the syringe was washed out with well wate^, rinsed in distilled water and boiled in distilled water. From time to time additional distilled water had to be added to the sterilizer. At the end of the day's work, the residual water in the sterilizer containing the non-volatile accumulations from several sterilizations, was poured into a sample bottle for preservation and analysis. Gallon jugs for samples of urine and beverages* and quart jars for faeces and solid food materials* and small "bottles for blood and other small samples had been prepared and sealed in the laboratory in Cincinnati* and had been shipped by rail to the nearest point. The final lap of their journey was made on the backs of burros. They were stored in a dry adobe house* from which they were given out to the subjects for immediate use and immediate return to the custody of the caretaker. Each subject was provided with an identification card which showed his name and number, the jugs and jar3 having been labeled correspondingly. At first difficulty was encountered in introducing the idea that the urine samples were to be provided by single individuals. In some instances the identification cards were passed to other members of the family of the subject in order to expedite the conclusion of the work and the obtaining of the fee. This was not so much an intentional deception* as a lack of understanding of what was desired. When the language difficulties of the situation are considered, and when some inkling of the absurdity of the entire situation from the point of view of the Mexican is appreciated* the misunderstanding is not surprising. On the whole, however* th collection of the samples - was satisfactorily accomplished, with only the occasional mishap of mixing- the urine of more than one person in a single container. In a few instances recorded in the data* the samples were so small that they were combined to "Ti1 OT"-{ o lu * make composite samples. The food samples were collected directly into the jars. Upon the completion of the work* each sample was treated wriitffei'^sS to A 10 c.c. of 40% formaldehyde which had been shown by analysis to be free of lead. The containers were sealed* packed in crates and shipped back to the Cincinnati laboratory for analysis. Thr^uglt-tlie x u u r .cut,turns-- i1CL\'\t,A^KsQ r.isqxa^ i^wAa-pg>.aalbi a to. have them Cincinnati in the presence of a member of the laboratory staff. Thus no opportunity was given for the -contamination of any of the materials from the time they left the Mexican ^Cincinnati laboratory for analysis. Through the ourtesy of // customs officials it was possible to have them delivered to // the analytical laboratory without breaking the/seal on a , i \ i j single container, the customs inspection having been made * in Cincinnati in the presence of a member or the laboratory f staff. Thus no opportunity was given for ihe contamination / of any of the materials from the time they left the Mexican / village until they arrived in the laboratory*------ -"77 " I la Jf'.f safaf C m ***&S Tables to -XV-T inclusive^ LMi 'hiLu fnn.niyltif*.Hi a h a S o i l samples taken at random in the fields under cultivation (Table xtri) uniformly show small amounts of lead. Since there had been no opportu nity for surface contamination of the earth by artificial means, these results give some idea of the natural lead con tent of the soil. No doubt there are wide variations in different parts of the earth, but Y/herever soil is produced , by the leveling of mountains, some small quantities of lead nay be expected to be found. Similarly, the water contains minute traces of lead. Table 3i3rl shows that the vegetation 4gg absorbed small amounts of lead.---""n _ .- -- - X aJ32L,,.______ -- -- 4r In the case of prepared foods (Table it is necessary to consider the opportunities for the introduction 3 of lead from the use of pottery. Table XVIII demonstrates the lead-glazed character of the pottery which was being used generally in the two pueblos. Certain of the animal products, such as eggs, fish, lizards and crawfish were obtained in a raw state and are not to be classified as prepared foods* Table XVI Lead In Soil and Water Article CACHI r ' it COLERO ! tf& c Found 10*1 Found"j (fo^ n j Quantity! Tigs. -\ 1 j1 \*& /& & \ Quantity) Mgs. ------ ---------- -- ;-------- \ !, ' ! 7/ell Water (drinking) .i 3500 c.c. 0.03 Water from Stream(washing) 1 3240 c.c. 0 .0 0 Soil # 1 .. |! 'h.aoifu^ o, 1X Soil 2 Soil #3 &-.;v^ o-H 0.000/Li 3900 cc; . n j 1" m i 0 . 0 0 ~~~| 3860 cc - t v > [/ - f w * * /,4 o "'i 0.03 0.03 t 50 j0.Q09# 0.009$ </,C,0 ofo 001444G Table XVII & Natural Lead In Vegetation Used as Food Materials Articles CACHI Weight Pb.Found p v ^ C O In Gins. Mgs* .as. ;Weight ; In Gms COLERO ..... v . ... Pb.Found ?b^;0rr Mgs. Wheat (dry) 99 .40 `heat (green) 146 .40 Corn (dry ....... 330 .70 Corn (green) #1 161 .20 Corn (green) #2 217 .00 Corn Stalk (green) #1 i 183 .20 Corn Stalk (green) #2 j;215 .00 Corn Husks (green) j!227 .20 Peas (green) j Pea Pods (green) j Eeans (dry) Beans (Haba) (dry) ;273 .00 :l Beans (Haba) (green) 116 .00 Pods (Kaba) (green) i175 .00 Leaves (Haba) (green) :133 .30 Pears (green) Apples (green) 249 .50 Peaches (green) 1243 .70 Nopal #1 ' 149 .30 Nopal 4r2 214 .40 Squash (green) . . . . . . . . . . . . . . . . . . . . . 121 .00 Squash Plant Radishes Turnip Leaves................ t Peppers 'i Greens #1 ' 85 .70 C-reens #2 Capulin (type of cherry) t 0.04 .....O-tO 0.04 olfa o.ii. . . . . . . . . .o.fj 0.05 0.03 . o-SF o.f4 2 ;3 3 1 O CO. 0 .01 o.o3- 0.02 0.01 o.ff- ,275 . 0 0 0 .0 5 -- > 0 .02 6.0 5 0.06 0.2i(o !I !291 .20 . . . 0 .01 .. 0 .0 5 - 0.11 0.03 0.00 0.00 0 .44 0 .-2& 0 .0 0 0 .0 0 ;!193 .00 ..0 .01.. . . . . o.gr- j 175 .40 0 .07 0 .40 :213 .30 0 .03 0 .74 i256 .50 0 .04 o.r |283 .80 .01 ": ;218 .10 0 .04 o.fjg 0.03 0.02 . a ; o.bS ;262 .80 0 .01 o.ov 0.00 0 .0 0 231 .10 0 .01 o.o- 0.01 0.04 0.00 iJ 0 .0 5 *- : 128 .60 0 .03 0 .5 ^ :i335 .60 0 .01 ;j 71 .20 0 .02 . . . j 54 .80 221 .50 0 .01 0 .00 32 .00 0 .03 0 .0 0 224 .60 ; 0 .01 80 .70 ; 0 .00 215 .90 "0 .01 0.2i3 0 .0 3 0 *2 $ o,p% 0.00 0.04o.r0.00 o.or- 001444? Table XVIII Lead in Pottery Used by Subjects Sample CACHI Weight +.'-(& Pound In Gms. Mgs. Percent COLERO Weight jJffid Pound in Gms. Mgs. Percent Glazed Dish Glazed Dish Unglazed Dish 1*00 8.20 0.82 1.00 1.00 1.00 13.00 12.50 0.10 1.30 1.25 0.01 0014448 Table XXX Lead In Animal Products and Prepared Pood Materials ' Articles Atole - (barley-corn VMt*) C o m In Lime Solution Corn ground for Tortillas Bread Tortillas Tamales (corn) Chicken Eggs - Hen and Turkey Boiled Pork Pork Sausage > La?j$; (pork) Beef Chili (with meat) Cheese Dried Pish Fresh Fish Ajolotes (lizard) Craw Fish Common Sait Candy (local type) Pulque Aguamlel Wine CACHI Weight Pb.Found in Gras. Mg s . 417.50 0.00 445.00 0.04 117.20 0.02 119.40 0.07 503.40 411.70 0.00 0.03 3300 cc 0.14 COLERO Weight Pb.Found p't in Gms. Mgs. 0.00 409.70 1.70 f-lS 0.0$ 544.00 0.10 oM 0.{$ 265.70 0.03 0.<f i o.$$ 73.70 224.80 0.07 0.08 45* o .f 283.30 0.01 0. 419.80. 0.00 0.00 0.00 471.50 0.01 0.0% o.of. 492.10 0.00 0.00 73.80 0.02 0.1% 54.70 0.00 0.00 o 121.80 0.02 324.40 0.15 o.^& 84.40 0.00 0.00 26.50 0.04 80.90 0.02 0 207.80 186.90 0.02 0.14 o.\ o.q& 204.60 0.21 MZ 277.60 0.08 o.m 0.04^ Sample Lost 3760 cc 0.06 0.02$& Thus any lead found in them is of natural origin. In fact, only two of the articles listed in Table XIX, show amounts of lead which indicate the likelihood of significant con tamination, namely, the pulque v/hich probably took up some of its lead from earthenware vessels, and the atole, one sample of which is grossly polluted with lead. The latter circumstance may have been due to the unrecognized presence of small fragments of the earthenware jar in which it had been kept, since such jars are very fragile. 5 / & / "7 , F, `T Tables XX, XXI, XXII, XXIII, and XIV, display the lead findings in the two groups of subjects. Only eleven of the thirty-two blood samples showed the presence of lead, and in these the quantities were small, but measureable. because of the minuteness of the quantities of lead^which were at the lower limit of analytical as-tm auLon, the entire volumes of the last five positive and the last three negative samples as finally prepared for the colorimetric determination, were preserved for re-examination. ^Twenty-three samples had been completed and the solutions had been discarded before this procedure was decided upon. The two sets of combined samples were evaporated down to the required amounts for colorimetric comparison and a re-estimation of the total lead v/as made. This same process was employed in checking the quantities of lead in all other types of samples, the results appearing in Table XX^IV. Thus, despite the wr.ho quantities of lead Involved in the entire series of analyses, there can be no doubt of the presence of lead where it is reported to have been found.) It is certain that the lead Table XX Distribution of Subjects According to Lead In the Blood Lead in Milligrams per 100 Gms . Blood Number Percentage 0.00 0.01 - 0.02 0.03 - 0.04 0.05 - 0.06 0.07 - 0.08 0.25 21 6 2 1 1* 1* 65.6 18.8 6.3 3.1 3.1' 3.1 Total 32 100. ,- i.. 1 ! /Tjf S'. , f_ *yLm '1* if J K 0014451 Table XKI /tj l^xZ. J Distribution of Subjects According to Ameun ts of Lead !- Urine COMBINED GROUPS CACIil COLERO yY^JL* - w ^ '***} o v yyv Liter of Urine Humber Percentage Humber Percentage Number Percentage jaj&f Q 0.009 0.010 - 0.019 0.020 - 0.029 0.030 - 0.039 0.040 - 0.049 0.050 - 0.059 0.060 - 0.069 0.070 - 0.079 0.080 - 0.089 0.090 - 0.099 0.100 - 0.109 0.110 - 0.119 0.120 - 0.129 37 45.7 19 45.2 18 46.2 26 32.1 10 23.8 16 41.0 10 12.4 8 19.0 2 5.1 ? GO 4 4.9 2 2 5.1 o 3.7 2 4.8 1 2.6 1 1.2 1* 2.4 Totals 81 100.00 42 100.00 39 100.00 .Mean... ... ...... ... ..( o T o i .*~^re&... toroide {o.or? * ?-v' _ ir/). ooc`% o,.ootz. _ to. o\o _ S tandard D e v W . ^ .... .. .+0.0105 ....._......... 0.0114 ......... 0.0095 ~ * These include two composite samples made up of the urines of two groups of children. Omitted in calculation of mean* Distribution of Subjects According to Milligrams of Lead per Gram Ash of Faeces COiiEINFD GROUPS CACHI COLERO Humber Percentage Humber Percentage Humber Percentage o $ 0.019 0.020 - 0.039 0.040 - 0.059 0.060 - 0.079 0.080 - 0.099 0.100 - 0.119 0.120 - 0.139 14 16 0.18 - 0.199 . 20 22 24 0.26 - 0.279 0.28 - 0.299 28 21 13 5 4 j?r 2 1 it 1 1 36.9 27.6 17.1 6.6 5.3 a*er 2.6 1.3 1.3 1.3 19 9 6 4 O Jdr~~ -0~- 47.5 22.5 15.0 10.0 5.0 il*0-Sv- 9 12 7 1 2 2 25.0 33.3 19.5 2.8 5.5 ' 1i^rj|"0 'rri---` 5.5 1 2.8 *0-.'O' 1 1 2.8 2.8 Totals 76 100.0 40 100.0 36 100.0 ...Kean. s . " " d . ... Jo 7o 347 -in-e^eeeg. ___i O._02Z._ .... +-.28 003(5j5 0 r0086*-~ JO.03^7 * .Q+Q03g ' 0. >`> ' .....*o. cosy + 0 . 0 2 4 3 .... 0.0312 Table XXIII Distribution of Subjects According to Lead Found in Faeces COMBINED GHOUPS I CACHI j COLERO Humber Percentage /Humber Percentage! Number Percentage -il 0 - 0.019 0.020 - 0.039 0.040 - 0.059 0.060 - 0.079 0.080 - 0.099 0,100 - 0.119 0.120 - 0.139 0.140 - 0.159 0.160 - 0.179 0.180 - 0.199 0 . 2 0 0 - 0.219 0.220 - 0.239 0.240 - 0.259 0.260 - 0.279 0.280 * 0.299 0.30 - 0.319 0,40 _ 0.439 1. 0 0 - 8 10.5 6 15.0 .... 2 .. ... 5 . 5 .. 7 9.2 5 12.5 2 5.5 9 11. 8 8 20 .0 1 2.8 7 9.2 5 12.5 2 5.5 4 5.3 2 5.0 2 5.5 9 11. 8 4 10 . 0 5 13.9 7 9.2 1 2.5 6 16.7 6 7.9 1 2.5 5 13.9 2 2 . 6 2 5.0 0 0.0 3 4.0 2 5.0 1 2 . 8 3 4.0 2 5.0 1 2 . 8 1 1.3 0 0.0 1 2 . 8 3 4.0 1 2.5 2 5.5 2 2.6 0 0.0 2 5.5 0 0.0 0 0.0 0 0.0 1 ...... 1.3 1 2.5 0 0.0 3 ...... 4.0 0 0.0 ; 3 8.3 1 1.3 0 0.0 1 2 . 8 Totals ?ean /"- . > r1 76 10 0 . 0 fci7l078 * O-OOS ' 0 . o'S^i j 0.0741 40 100.0 . 36 10 0 . 0 ,( M j____ -W jo!0900 -V -- JoT130 G-.-OG83-- 1 ; 0 , 0 0 7 7 i: i0.0 0 73 i 0 .0725 j 0.0700 # Omitted in calculation of the means KE 0014454 Table XXIV to Summation of Analytical Results as Compared to Amounts Obtained by Composite Analyses Description it* u u r CACHI COLERO t Sum of :\ Sum of Clumber Individ- Number Individ- of ual Compos ltdj of | ual Composite Samples Findings Analysis!Samples ^Findings Analysis / vVKJ ^ltZ*i GO./*.' /POS , .. 5*._..___ 0.05.. ... 0.08...: -------- - {''eg. . 3::- . .. 0.00.. ..0 . 0 0 : - '"?os. 22if . 0.78 ...- 0.85 .j 32 1.41 .1.51 ;N e g . ; 3-::-. .. 0.00.. ..0 . 0 0 j 7 p o s i f 12 1.02 1 . 0 2 1 36 6.15 0.00 5.75 00 0. 0 00 PeedTMSaaple-s $ PVjS v ' 1-- j--'C - * - Fond"SampTs 3 Total -f P o s . ; 19 Heg 1i 7 72 0 .9 7 0 .0 0 2 .8 2 0 . 0** 0 .9 3 jj 3 4 i !9 2 .9 2 118 ....................... . j .................................. ........................... -- --- *-- - .. 3 .1 7 1 0 .7 3 2 .9 7 0 .0 6 1 0 .2 9 * Material from other samples was discarded when.indiv idual -aftalyajiH W&g.._cnffie4resd.r pi <=>^ ^ <*ri^^r^p^ekiJ^bm*^^3-y^vrri^T^Pr^^p*i^rr^^*ririnm. ## Only three negative results were obtained on faecal samples. The t^te-r-tel-j^a?3-^i^caT:fded<~~befere^^h e.adg^hion",iu'f"-blre.p-3rn-- to..d o oas poaiJt^analy&e. found by analysis was in the blood as withdrawn from the veins of the subjects, for any suspicion that contamination may have occurred is oomplcJhadry dispelled by the fact that the three samples of residual distilled water from the sterilizer failed to show traces of lead. 'Table detailing the analytical results obtained on the urinary samples, shows the mean values of the lead ex- cretlon per liter of urine for each group as well as;Athe com bined group of subjects. Here, again, the results were low but the volumes of the individual samples were so large that the amounts of lead generally found, were within the limits of accurate measurement. The volume of the average sample was over three liters, many being four, and only a few less than two liters. The accuracy of estimation of the smaller amounts is attested by the result of the composite analysis which appears In Table The urinary excretion of lead is of the same ma ;% g_n itude in th. e two groups of subjects, as shown by the meanly Despite the comparatively small numbers of subjects the means are so stable as to indicate only a small variability in the experience of the subjects as regards lead absorption. The excretion of lead in terms of milligrams of lead per gram of 7 ash in the faeces, (Table XXII shows a slightly greater invariability, but the two groups of subjects are similar uJkthis regard, and may not be differentiated statistically ' 'comparison of these mean values with those obtained from the study of the medical student (cf. Tables VII_.and VIII) , brings out the surprising fact that they are of the same order of magnitude. Evidently the ingestion of lead by persons living under these natural and primitive conditions, is not -widely divergent from that, experienced by certain individuals in an American city. The evidence provided in Table XXIII leads to the same condlusion. The quantities of lead actually found in the samples reach a mean value of 0.108 milligrams of lead for the entire group of subjects. On the whole, the single samples represent not more than one day's alimentary output, while the lead content may be assumed to be something less than that ingested during the previous day. In these terms the mean daily ingestion of lead amounts to a little more than one tenth of a milli gram of lead. This value of 0.108 mili4gruiirs" in the Mexiean subjects is to be compared with the value of 0.187 arrived at by similar methods in the case of American subjects. A slightly different basis of comparison may be made by calculating the mean daily output of lead in both urine and faeces. Assuming that the mean lead content of the faecal samples constitutes the alimentary excretion for a day, and that approximately two liters of urine are voided daily, the average Mexican excretes approximately 0.14 milligrams of lead per ,V day, as compared to 0.33 milligrams for the American. The unavoidable conclusion to be drawn from these facts is obvious. Despite all the opportunities for the artificial contamination of food materials with lead in American cities, a large proportion of lead 7/hich is ingestdd by the average American is derived from natural sources. A classification of the Mexican subjects on the basis of 1 'C. . their ages, as portrayed in Table XXV, shows that a large number of children were included in the groups. An opportunity is thus afforded for the comparison of these children with the adults of their own type, and with American children. Table XXVI gives the analytical data, for children up Table & & T ' Distribution of Subjects According to Age Age in Years 5-9 10 - 14 15 - 19 20 - 24 25 - 29 30 - 34 35 - 39 40 - 44 45 - 49 50 - 54 55 - 59 60 - 64 65-69 70 - Totals Combined Groups 30 13 7 4 14 6 6 4 1 2 2 3 1 2 95 Caehi 16 2 4 2 8 5 5 2 1 1 2 2 1 2 53 Colero 14 11 3 2 6 1 1 2 0 1 0 1 0 0 42 K 0014458 Table XXVI -\ ' Distribution of Children && to Lead Found In Faeces, Lead In Milligrams per Gram Ash of Faeces, and Lead in Milli grams per Liter of Urine Lead Findings Milligrams ;Number of Subjects as Number of Subjects as Number of Subjects! ijto Lead Found in Faeces! to Lead in Mgs/Om Ash to Lead in Mgs/L.Urine jCachi Colero Combined] Cachi Colero Combined Cachi Colero Combir 5.10 - .0 .0 1 9 2 2 4, . . 0 .0 2 0 - 0 .0 3 9 2 24 0 .0 4 0 - 0 .0 5 9 4 .1 .5. 0 .0 6 0 - , 0 .0 7 9 2 13 0 .0 8 0 , - 0 .0 9 9 1 ...1 ..2 J0,, . 1 0 . - 0 .1 1 9 22 0 .1 2 - 0 .1 3 9 11 0 .1 4 - 0 .1 5 9 22 0 .1 6 - 0 .1 7 9 0 .1 8 - 0 .1 9 9 11 0 ^2 0 - 0 .2 1 9 0 .2 2 - 0 .2 3 9 11 0 .2 4 ...........- 0 .2 5 9 1 0 .2 6 - 0 .2 7 9 11 55 45 12 11 1 1 10 9* 12* . 21* 9549 3 2. 1 1 11 Totals 12 15 27 Means {Combined Groups!) S. D. ......."...".. 1 0.0 881 * - 0^ 0 0 9 3 - ..........! + 0 .0 7 1 2 12 15 27 {70396 _XU006S~ -...... 0 .0 4 0 9 ' ' * Only six of these are nil, two from Cachi and four from Colero. Calculated after a wider distribution of findings. to nine years of age. The numbers of subjects are too small to permit statistical treatment of the individual groups, but the means for the total number of children from the two /a-M./)l.t.-CUU-tc*/ villages are stable. The means are not ^ dif ferent from those of the entire groups to justify calcula tions on the adults alone. On the other hand, the urinary , >. lead excretion of these children is significantly, lower than that of the American children, though their faecal excretion, while considerably lower, Is not significantly so from a statistical point of view. The importance of the observa tions on the Mexican children arises from the fact that it Is not necessary to consider the possibility of any sources of lead ingestion external t o 'their pueblo. They had spent their entire lives up to that time in the immediate vicinity of their native village. . The examination of blood smears made from these subjects establishes a fact which is of some consequence in relation to lead absorption. Tiuch discussion has con- Vvi iy ` l/ ceiUed Itself .with the question of whether stippling of the erythrocytes occurs in normal persons. Table XXVII answers the question conclusively and affirmatively. There can be no question of any relationship between significant lead absorption and the presence of stippled erythrocytes in the blood of these subjects. On the other hand, there Is a difference In the people of the two villages in this regard. For some unexplainable reason a considerable proportion of the blood smears from Cachi show numbers of stippled erythrocytes which would be generally regarded as Table XXVII Distribution of Subjects s*s to Stippling of Erythrocytes Number of S tippled|: CACHI COLERO Erythrocytes per iI<------- i: 50 Fields 1Number Percentage Number Percentage ! i! ..;. . sj. _____ CL 4P 3....... ;..28.. _ ... A 'L . ..4 ** 7 .8 - 11 ... 12 - 15 : 12 .... ? !> ... jit <: i! ; 3 ...: .. V/-7"v1 .... ' i 3 , 0.* 1 3 8 . .!.. o*-* ; 1j ... 16 - 19 20 - 23 24 - 27 28 - 31 32 ~ 35 .... 36 mm 39 40 - 43 .. 44 - 47 50 - S3 54 - 57 74 - 77 Total ! 5 ;1 \1 3 i;h t1 1 J1 i } 1!,, . i1 i \ ! :2 i i .............................. i i 60 i -3 /.7 _ i:u S . l, 7 - 7- 3.3 /w> '\, ; H i- _ i1 11 ! i [I ?! ?!;i if M tnl !j If u J1 1! 1 if.: >7 u l; 42 : 4-3 . Z .7 . 2 .2 / V? K 001446 i Table XXVIII Distribution of Subjects According to Haemoglobin of Blood Haemoglobin Reading(Dare) '-'-='63 65 - 69 70 - 74 75 - 79 80 - 84 85 - 89 90 - 94 95 - 99 10 0 - Totals CACHI Humber Percentage 3 5.1 17 28.8 13 2 2 . 0 15 25.4 9 15.3 1 1.7 1 1.7 59 10 0 . KE" 0014462 of diagnostic significance, under* conditions of lead exposure. The smears from Colero were mostly negative, and uniformly low. The presence of secondary anemias in the inhabitants of Cachi might be expected to produce such a result. However, the subjects in both villages Y/ere healthy, and the haemo globin determinations in Cachi, shown in Table XXVIII, do not suggest the existence of any considerable incidence of anemia. Furthermore, there is no correlation between the amount of 'stippling and the haemoglobin reading. These facts lead to the conclusion that stippling occurs as a normal phenomenon^ of unknown physiological significance. This statement of fact must not be Interpreted as a denial of the practical value of blood examinations In the case of workers In the lead trades. Data which will be shown later demonstrate the Im portance of such observations in obtaining presumptive evidence of lead absorption. Nevertheless, considerable caution must be exercised in drawing conclusions from such information, even under the most suggestive conditions. KE- 0014463 Chapter III The Sources of Lead Absorption In the Modern Community / V ? The uniform occurrence of lead in the excreta of normal individuals indicates a general distribution of lead compounds in the normal human environment. The quantities of lead In the urine are so small as not to be demonstrable by the analytical methods employed by most of the earlier investigators. Thus there is no adequate basis for an assumption that this is a phenomenon of modern life. Evidences to the contrary are to be found in certain observations of the lead content of food A/ and drink, a s early as 1881, Gau-fc ierv determined the lead content of many food materials, by satisfactory chemical methods, and concluded that the average Frenchman was Ingesting approxi mately half a milligram of lead daily. In his opinion the prln- . clpal source of lead U jj&JL** cooking utensils and preserving cans. Other facts, mostly of a fragmentary character, tend to demonstrate that such factors were not the only ones involved. Fuller reference to these matters will be made later. But it need not follow that present conditions are the same qualitatively or quantitatively. The modern technique of handling food is very > different from tv,at of the nln^eenth century, while many other matters of everyday life have seen revolutionary changes. There fore it is necessary to examine(the^conditions In the modern com munity In some detail* K 0014464 2 / We have chosen to approach this question by a less laborious method than that of systematically studying the lead content of foods and other materials with which the individual has contact. It appeared more advantageous and more interesting from a physiological point.of view, to ob serve human subjects under certain sharply defined variations in environment, thereby obtaining simultaneous Information as to the environmental factors and the response to them. A study of the lead excretion of infants and children was made on the possibility that the limited length and quality of their experience might be associated with an obvious limita tion of their contacts with lead. Observations on adults under carefully controlled conditions supplied further varlunts. 1. Lead Excretion in. Infants and Children. Children were taken at random from various services in a children's hospital, care to exclude such as were sus pected or known to have had exposure to lead compounds or a history of pica. Those with acute Illness were also avoided. In so far as It was possible, samples of urine and faeces were col n l lected directly Into the containers, In some Instances this could not be done. The precautions taken were such as to avoid the likelihood of contamination of the materials with any lead bearing materials. /v . A' Table TV shows the ages, the gounds for admission to the A- hospital, and the lead findings In this group of children^ / the mean values for the excretion of lead in ,*- V V ' - A ; ' '.r.\ ' , v ? .'V` 4 A s S '. i h J 4- L- M^y "*'f '"-'iVTr t x Z & ""' V \ r ;' : :4T'yxf44 `VV\^V? ...... I w k i >'Vyr*:><.4;.-,iyw4<t-MfAyr. ^moJz.OOSVk ' / . V ''--r, - . ' .4Mis'f?,t?' 'Vt7J? / .V 0 ~.oz<f 35 f 4 -- -o . ' Of -,//? /& - / Vf? / r **/ 7 f ' /i - a Jo <? . 5/ ~ 3tf -r > ,/ -2 c'Siyj , y. , '*' o' . * . O V /o ' /% n / . ;o ._ i_ ?X ' r,Hwrj'i! 0 / <3 'V. "<3 36 ? - > 3 7^ - 7rr jt >O 5* *+ "0/ ^ 3V 1'4- V TV * T * , n ^ l O S * ,0$o 3 ~ >3'X rf.sf k.fcSi-VS" - , 1 7 0 V ; - w y s * cp ' ,3* CjD- ^ "4 O o S-tV* ? ,03 \i S,* ,(piy-4q ' ' 0 V S 9 iHfJOBWn Il *. . --' ? * 0 / 3 ? tol , . 'JhsxiAcyyyr'Ot02o3 ji: tos~o% ,/. ? to.otncf CP Table w Lead Excretion in Normal Children Hospital Identifi cation No. Description of Case or Diagnosis Gal* 'L Lj&>* LEAD IN FAECES LEAD IN URINE Mgs . Mgs/Gm Found Ash Mgs. Found Mgs./ Liter .90 245 . 970 Y 2130 2330 2504 .2582 2783 2375 3043 3091 3119 3337 3377 3387 3528 3531 3532 3604 3691 3695 3698 3703 3706 3726 3763 3779 3780 3846 3866 3874 3887 3901 3967 4020 4026 Orthopedic Treatment 9 Chorea 8 Cardiac Lesions 7 IPost-Oseraitve. .Ci>w.yafesW***Cl' 5 Cardiac Lesion 10 Orthopedic Treatment 12 Convalescent Polio- .4 Orthopedic Treatment 4 Convalescent Fracture 4 Astragalectomy 9 Osteomyelitis 11 Post-appendectomy 7 Eczema 1 Chronic Appendicitis 14 Osteomyelitis 7 Mastoiditis 6 Dietary Regulation 0 .6 Oesophageal stricture 7 Chorea 11 Post-anpendectomy 11 Osteomyelitis 10 Post-appendectomy 12 Anemia (type?) 5 Post-appendectomy 13 Otitis media - nephritis 12 Arthritis 6 Post-appendectomy 12 Convalescent Fracture 12 Alkaptonuria 0.25 Convalescent tonsillectomy 8 Post-appendectomy 11 Convalescent^-burn 6 Mastoiditis IS Chorea 8 Orthopedic Treatment 7 Tonsillectomy 8 0.30 0.27 0.27 0 . 10 0.38 0.61 0.05 2.22 0.62 0.14 0.42 0 . 10 0.37 0.09 0.53 0 .21 0.26 1.57 0.29 0.45 0.14 0.41 0.43 0.17 0 . 10 0.28 1.28 0.24 0.23 0.60 0.39 0.24 0.23 0.70 0.90 0.06 0.17 0.09 0.08 0.03 0 . 11 0.03 0.23 0 . 10 0.13 0.08 0 .20 0.005 0*14 0.31 0 . 11 0.14 0.06 0.07 0 . 10 0.08 Nil 0.13 0 . 11 0.07 0 .20 0.03 . 0.24 0.06 0.13 0.05 0.18 0.03 0.13 0.19 0.04 0 . 11 0.37 0.05 0.24 0 .0 1 0 . 12 0.06 0.17 0.14 0 . 10 0 .22 0.03 0.17 0 .0 1 0.18 0.07 0.13 0,15 0.29 .0.05 0.15 0.15 0 . 11 0 . 11 0 .20 0.04 0.05 . 0.06 0.03 0.03 0.23 Osll 0.13 0 . 11 0.09 0.17 0.06 0.09 0.08 0.07 0.08 0.09 0.13 0.07 0.06 Nil 0.08 0.18 0.08 0.07 0.09 0 .1 1 0 .0 2 0.07 0.11 0.07 0.05 0.04 0.08 0.17 0.07 0.04 0.09 0 .1 0 ,0.39 0.12 0.03 0.04 0 .1 1 0 .1 2 0 .1 0 .f \l V . ,, v - i`\/ *vw Y -f . *. iT 0,0^0 O.OOiT o. 0. 0 .o r 3 the faeces and urine. The calculation of faecal excretion in terms of the total ash Is not entirely justified on a physiologi cal basis, for reasons which will appear later. However, it is a reasonably satisfactory arbitrary basis for quantitative com parison. In this case it is necessary to use some such means, for the reason that the faecal samples are not comparable on a, o time base. The constancy in the lead excretion in these children is sufficient evidence of the general and unavoidable character of exposure to lead compounds. Moreover, the magnitude of their lead excretion as compared to that of adults suggests either that lead Is excreted more readily by the young, or that time Is not an Important factor in influencing the extent of absorp tion under present conditions of exposure to lead compounds. It is worthy of note that none of these children showed . symptoms which gave even the vaguest suggestion of lead intoxica 4 tion. One of them had been breast-fed from birth. Thus the ~ /i possible sources of lead must be extended to Include the suck ling period and the gestation period. Accordingly the lead content of human milk was investigated in a limited manner. . The results obtained may not be regarded a3 a representative O cross section of the normal situation. They merely demonstrate that the ingestion of lead from this source may and does occur. The milk was obtained by manual expression, each subject having been instructed by visiting nurses in the matter of clean liness and general technique. The several small samples were collected and delivered fresh to the laboratory, where they were kept until a considerable volume had been obtained from each Table Lead Content of Human Milk ect No. 1 2 3 4' 5 Volume of Milk In c.c. Lead Found in 2031 ' 1936 2306 1230 2853 1 0.05 0 . 10 0.09 0.04 Nil 4 o subject. All'"of; the subjects we re housewives, with entirely negative histories in such matters as occupational exposures i/ to lead, recent illnesses, and recent-sour ces of medication. V XTable presents the results of the analyses. Our data on lead absorption during gestation confined >/ to "&*<* obtained on experimental animals, under variable condi tions of lead exposure. As such'tay f' present matter except in so far as " ^ 1 not apply to the that lead absorp tion in the pregnant animal is associated with lead absorption by the foetus. However, furnish/:', presumptive evidence that human beings may be born with lead in their tissues. \ n "s \ S3 JA .' i U-" -Tu"-1' ' I -I f* V '\y' ' / i 1/ ' * , . .V. ^ ,!a K ^ :f, i ` 2. Lead Ingestion and Lead Excrtion in a Normal Adult. y' ^ 1 - A healthy medical student v/as selected as a subject for 1V- ,;ih-^t-V ^ y ^ daily observations over a long period of time. His understanding V& / of the character of the problem provided the intelligent care ,sii and cooperation' for prolonged study. He kept a diary of his A, activities and movements about the city and the College of Medi cine, in which he also recorded his food Intake together with its source* Except for specific instructions from time to time, he selected his food according to his own wishes, and but for condi tions imposed for experimental reasons, his entire life was that of a normal junior In the College of Medicine. The results obtained over a period of a year are graphi cally illustrated in Figures 1 to 7. m Jtfj I i31J i <s 10 :l :J :* Fig. 1. Lead Excretion In a 'Normal Subject ^ j, iz a The blocks represent consecutive daily observations. The small solid black blocks at the top indicate lead determinations on sam ples of 50 c.c. of blood. They do not extend Into the field of the graph for the reason that the quantities of lead found were insuf ficient for accurate measurement. The upper section Illustrates the urinary findings, the stippled area indicating volume of urine, the solid block the lead found in mg3. In the lower section the cross-hatched portions represent lead found in the faeces, while the solid blpck gives the lead in mgs. per gram of ash In the ]: faeces. The dotted line records the average levels of faecal ex- ' cretion of lead for the periods over which it extends. v- The observations made from the fifteenth to twentieth days inclusive have been omitted on account of acci dental loss of the urinary samples for this period. AL t M il u v+vv*rct?s&jsiw 11+Ai66taaai <k>^ -l < -j 9**1ss * >01 Fig. 2 . Lead Excretion in a Normal Subject The blocks represent consecutive daily observations as an uninterrupted continuation of Fig. 1. KE 0024472 Three matters- of special note may be seen in Figure 1. ' 0 ad The urinary excretion at the start Is almost negligible, but A when an increase In urinary volume Is brought about by in creased water intake it becomes significant, though variable from day to day. The faecal excretion^starts out on a much higher level than the urinary, and Is subject to wider varia tion. It is clear that these variations are not referable entirely to variability of the mass of material excreted, for if such were the case the milligrams of lead per gram ash of faeces would be much more nearly constant. (The weight of ash is not an entirely- reliable measure of the quantity of faeces, but experience has shown it to be the most generally satisfactory manner of expressing quantity.) Figure 2 shows the introduction of two changes in the activities of the subject. He was Instructed to discontinue the two quarts of milk which It had been his dally custom to taket*^--- --- rrly. A slight brief rise in the urinary excretion of lead coincides with the day of discontinuance of milk. The faecal excretion also, shov/s an elevation, With Irregularly # spacedjvery high peaks. That neither of these changes A&; di rectly due to the elimination of milk from the diet will appear later. Then dally vigorous exercise was carried out for three weeks. There is a definite rise In the urinary excretion, v/ith resumption of the former level on the cessation of exercise. On the basis of the preceding rate of urinary excretion one would certainly ascribe this change to the influence of exercise. j new of Urine Lid M ^_3 il I ~Sk ! ~I l Pig. 3. Lead Excretion in a Normal Subject The blocks represent consecutive daily observations as an uninterrupted continuation of Figures 1 and 2. * This result of 0.14 mg, is an entirely ab normal one. The concentration of lead in the sample is' 0 . 2 2 mg. per liter, and is higher than any obtained in the entire series of observations. Without doubt it. is due to the contamination of the sample in some manner. K 0014474 However, a similar rise in the urinary excretion of lead, without a corresponding change in the experimental procedure, as shown in Figure 3, casts considerable doubt upon the validity of such an enterpretation. In fact the general level of urinary excretion is notably high during the entire period represented in Figure 3. The explanation of this sit uation may be found by examining the faecal output of lead from the begin ning of the observations through Figure 3, Beginning with the 54th day of observations (Fig. l) and continuing up to the 149th day (Fig. 3) there is a maintained high level of faecal lead excretion such as is not shown in any other normal period of the study. This suggests the existence of a factor which is so much larger than any other in its influence upon lead excretion in both faeces and urine as to completely mash the effects of other experimental measures. This factor is wi-th.- the quan tity and quality of ingested food. It may be noted that the faecal excretion of lead shows wide T T / Footnote: The very high figure obtained on the 124th day is entirely !;'Ji Lj U ~ .T M\ '`dt v 1 unlike any other result obtained during the entire study, and hence\is |' \ Ij probably in error. This figure of 0.14 mg. in 630 c.c. of urir^e repre- ; : ; - ; / I sents a concentration of 0.22 mg. of lead per liter of urine. Such a .' t concentration;is not' found in the urines of normal subjects, anfij it does li ;/ ;/ / \ not occur again in/this subject, even when lead was administered for\ \\ v/ ,/ i/ ' / experimental purposes, It must be the result /of contamination of the w v J , - sample at some point in its collection or analysis. K f 0014475 fluctuations from day to day, without any exact correspondence with the daily level of urinary lead excretion. On the whole, however, periods of several days in which the faecal -excretion is high, are associated with corresponding high periods of urinary lead output. The significance of the wide fluctuations as well as the generally large magnitude of the faecal excre tion becomes apparent in the observations shown in Figure 4. Thus it is only necessary to point out that the notes kept by the subject indicate that for the periods of time represented in Figure 2 and the first half of Figure 3, the food intake was practically doubled $ >f the period shown in Figure 1, This was the result of longer working hours, shorter hours of rest, and changes in food sources. During the obser vations of Figure 1 the subject was at rest. At the beginning of Figure 2 he began to exercise daily to a moderate degree. On September 1st (Fig. 2) he began working on the hospital obstetrical service, being on call day and night. At the same % time he took vigorous exercise by playing tennis through the greater part of the afternoon. On September 15th he began working on the hospital receiving ward. During this period vaccination against typhoid fever resulted in a severe reaction (first injection) with an evening temperature of 103 F. on ,a- two successive days. On September 23 regular classes in the Medical College began, with the necessity for establishing a new routine. During this entire period the gross solid food intake was high not only as a result of activities, but also as a consequence of the discontinuance of two quarts of milk daily which, had been an important, item of diet previously. Just how much direct effect on the lead excretion was produced by the discontinuance of milk and by exercise cannot be determined. A glance at the high findings during the ab sence of milk from the diet and at the lower results coinci dent with a return to the use of milk suggests a cause and effect relationship. In terms of the observations and con>/ elusions of Aub and his associates , this might be thought to denote a steady depletion of the calcium stores of lead In the body with the simultaneous elimination of greater amounts of lead during a period of loiv calcium intake, with an exactly opposite effect during a period of higher calcium absorption. Obviously^ fatiguing exercise would be^expected, to Increase the first effect. As a matter of fact, E i t h e r of these In- fluences 'h<a to have been exerted any Import aafr- because of the effect of the fr v i o a c;: - amounts of -W**! *"**>' wr^ - r The lead content of the food, as shown in Figure 4, was obtained by having the subject collect an exact duplicate of every meal during the period of such observations* For the greater part of the entire period of food analyses, no attempt was made to determine the lead content of specific foods. The entire bulk of three meals was treated as a single sample and analyzed, each meal having been collected In a quart glass jar. Because of the laborious character of the analytical work, such analyses were purposely omitted in the initial periods shown in Figures 1, 2 and 3. We nov/ wished to study accurately the Influence of administered lead on the rate of excretion. A double purpose was thus served In beginning the food analysis on the same date that we began to administer lead. On the day indicated by the first small arrow, the subject was given 1 mg. of lead as a solution of lead chloride in 50 c.c. of distilled water not less than half an hour before the noon meal. Every day for ten days the dose was repeated in the same manner, the oonclu3ibn of this period being marked on the graph by the second small arrow. The response to this small dose was immediate in the case of the urinary excretion, with a twenty-four hour lag in the faecal excretion. The urinary excretion may be seen to remain high during the period of experimental ingestion of lead a n d for four days thereafter. The faecal lead excretion, on the contrary, dropped off to a normal level in forty-eight hours, i.e. as soon as the alimen tary tract emptied itself of unabsorbed lead. The third small arrow indicates the termination of the time period for which the calculations of the inset table were made. Figure 5 carries on the daily observations without a break in continuity, showing the effects of the daily ingestion 03 of 5 mg. of lead in the form of the chloride, for six days. The first two small arrows delimit the period of lead adminis O CO tration, while the third marks the end of the time over which the data of the inset table were obtained. The three plateaus \t X in the graphic representation of the lead in the food of the subject arise from the fact that for these three periods, the J i' . weeks supply of each article of food was combined Into a single sample for analysis. The total lead found in all such samples Again) the response of the urinary excretion was prompt, and again it was sustained, this time for a longer period than that shown when the dose was smaller. The faecal excretion dropped off ftola linost) its normal level in forty-eight hours* just as before. ^The faecal excretion of lead during the period of ingestion and for two days thereafter is so large as to re quire a very much increased area for its graphic representation. For this reason the trend of the results has been indicated and the exact quantity of lead found has been noted at the top of the incomplete block. ^ The results set forth in these two figures are so cleancut as to require little clarification. They are so significant, however, as to justify some emphasis. First, the quantity of lead in the food is remarkably high. There was no reason to doubt the occurrence of lead In certain foods, but the discovery of amounts sufficient to explain the entire lead excretion of our subject, except during the periods of lead administration, was entirely unexpected* Second, the dally intake of lead is exceedingly variable.. Indeed so great is the variation that it djL is Impossible to interpret ^phanges in the rate of lead excretion^ except as this factor is adequately controlled. The matter will be given fuller consideration later, but it must be stressed, here, that the observations of Aub and his associates, as well rr as,others, on the factors which influence the excretion of lead must be reviewed critically with this variable in mind. This is especially necessary since the general acceptance of their conclusions rests largely upon the uncertain evidence of the varying lead content of the faeces under various experimental conditions* Another consideration of importance relates to the propor tion of Ingested lead which passes through the alimentary tract unabsorbed. Optimal conditions were present for the absorption of the administered lead, in that a dilute solution was taken at a time when there was the least opportunity for chemical reaction with the gastric contents. Yet slightly less than half the lead administered during the first period was absorbed, while more than two-thirds was eliminated unabsorbed during the second period. These observations furnish an explanation of the well recognized fact that heavy exposure for a short period of time is likely to be less injurious than a lighter exposure for a longer time. It may be calculated that if one milligram per day *wSTe taken for thirty days our subject would have absorbed not less than fifteen milligrams, while in six days at five milligrams a day he actually absorbed only nine milligrams. Thus if the same r> ^: A At.1 total quantities of lead wane administered, the absolute quantity absorbed would greater vmrnr^er small daily dosage ^ given over a longer period of time. The sensitivity of the level of urinary excretion to the magnitude of absorption is also sharply Indicated here. During the first period of administration, the subject apparently did not absorb more than half a milligram of lead per day. Yet the urinary excretion was measurably increased. However, in the subsequent period, the daily absorption was in excess of one milligram per day, and, though there was a definite rise in the l/HU) urinary excretory rate, yet there a- no distinct increase in rate over that of the previous period* That is to say -theb^-the j* ri*a z. m -ite J2c j n .1/t }& jjo j v j w jw * >Kr jfa jic .a i Pig. 7. Lead Excretion in a Normal Subject The blocks represent consecutive daily observation as an uninterrupted continuation of Figures 1, 2, 3, 4, 5, 6 . excretory rate is not substantially altered by differences in absorption of this magnitude. Nevertheless the period of heightened lead excretion is prolonged under the influence of the increased absorption. This latter fact is especially significant when it is observed that the lead in the blood during the two periods is not changed within the limits of sensitivity of the method oi observation. What obviously occurred was that the absorbed lead was so distributed in the tissues of the body as to increase their content without producing a corresponding degree of change in the concentration of lead in the blood, or the urine. Thus the period required for the elimination of the increased quantity in the tissues was prolonged# In Figures 6 and 7 the observations on this subject were concluded, three hundred and fifty four days having elapsed during the study. The study of the lead in the food was discontinued as shown in figure 6 , .figure 7 shows a period of three weeks of increased calcium intake, and another similar period in which twelve grams of ammonium chloride were administered daily, with an intervening period oi one week, neither procedure resulted in any noticeable effect upon the excretory rate. It may be seen that the lead content of the food diminished considerably toward the end of our period of study. The maintained low level of faecal excretion suggests -chat tne ingested iead remained low during tne remainder of the study. Furthermore, the urinary excretion of lead was almost negligible during the period represented in these two figurws. ables VII and VIII show the frequency distribution of the results in milligrams per gram of ash in the faeces, and per liter oi urine, together with the calculated means^ for^these items. Jite.iasgte percentage of negative, .1, F * f irrf t n e ' m e a n ' v a l u e of l e a d per' liter of urine, t W '> ff* "it, .-t-f-fetsC is_unhoubt.eai.y- due"^'ir'T?aVts'''tb`''th'e'''`'r,a'C't`^tn'ax'"the'--urine-'-wa8--oo-ileted- in t w e n t y-four h o u r samples, tfte v o i p e s of w h i c h in m a n y .instances.,were less Table VII Distribution of Urinary Samples ae to Lead In Milligrams per Liter Milligrams of Lead Per Liter of Urine Number Percentage to o. 0 - .009 .01 - .019 .02 - .029 .03 - .039 .04 - .049 - .059 .06 - .069 .07 - .079 .08 - .089 .09 - .099 .10 - .109 .11 .119 .22 179 44 33 16 15 7 5 3 1 2 1 2 57.9 14.2 10.7 5.2 4.9 2.4 1 .6 1. 0 .3 .6 .3 .6 .3 Totals 309 100. Mean s 0.01T3 O.OOf S.D. = 0.0ZO1 * Omitted In calculation of mean. Table VIII Distribution of Faecal Samples gap- to Lead In Milligrams per Gram of Ash Milligrams of Lead ' Per Gram of Ash Humber 0 - .009 . 0 1 - .019 . 0 2 - .029 .03 - .039 .04 - .049 .05 - .059 .06 - .069 .07 - .079 - .089 .09 .099 . 10 - .109 . . 1 1 - .119 .13 4 52 95 75 38 27 20 7 3 2 3 2 1 1 C0 o * Totals 326 Percentage 16.0 29.2 23.0 11.7 8.3 6 .1 2.1 .9 #6 .9 .6 .3 .3 100. Mean - 0.027 0.'00|2 S.D. s 0.020 fall-- to-^how-- amounts of lead, which ~are.capablna-o-t--aoeurate-quantlt a tive estimation, /or this ,reaserr-not"iess "thari'Two lTter s""isdeslrable"f the-- purpo.g_e,_Q.i'. each observation in a -stucty-tri-- trne"normaT 'excretion of .toad. ixte conctixions of tu s ,, X q regoing- ot>set*jvi*t-i-one"',were-tLeTi^se-d-with-a full recognition xnat tne limitations of.the analytical methods would develap,.,,an,,increased. importance in dealing with the samples of urine. thirs-giai-ter--is_c,.m.uch--.leas-signifrcance-- in-- the--c-&ee--oi-- the-- faecal sam- pl-es.. for. .thereason.that-1ha-1 arge-r-~quantiti"e3 of' Tea.d *present~reduce the-proportional analytical error. n ^ 1y 1TM value of the mean excretion of lead in milligrams per gram of ash is e^ieerio-^l-ewiir.^aJ.-eich^lead^exeretdioTr^i7nan "i'r--isBtomy-4rrrnormal sub jects. (Cf. Tables XIII and XIV) The combined facts indicate that during the latter periods of the experiment the subject had relatively little lead in his tissues, that he absorbed little from day to day, and that consequently he excreted very little. The importance of the information presented in the foregoing figures is heightened by certain further considerations. Thus if the day-to-day variations in the lead content of the food are leveled by calculating the mean daily intake of lead, and if the dai. ly excretion of lead in thefaeces and urine, exclusive of the periods of elevation occasioned by the experimental administration of lead, are calculated, the results are somewhat surprising. Tables XX, X and XI show respect ively the frequency distributions of daily lead in food, urine, and faeces, with the calculated means, while Table XII compares daily ingestion and daily excretion. It is seen that the ingested lead is approximately equivalent to that which is. excreted in the urine and faeces combined, the differences between their mean values being insignificant, statistically. : KET 0014485 Table ]Ji: Distribution of Dally Food Samples -a to Lead Content 10 i--1 iilllgrams of* Lead Pound in 24 Hrs. ' 0 m .049 .05 - .099 . 10 - .149 .199 . 2 0 ** .249 .25 - .299 .30 - .349 .35 - .399 .40 - .449 .45 - .499 Totals Humber 13 15 ; 33 24 9 5 4 0 0 2 105 Percentage 12.4 14.3 31.4 22.8 8.6 4.8 3.8 1.9 10 0 * Tiean s 0.147 0.006 S.D. 0.086 0014486 Table ^ Distribution of Twenty-Four Hour Samples of Urine tL&cvU.^ to Lead Content Milligrams of Lead Pound In 24 hrs. 0 .019 . 0 2 - .039 04 .059 06 - .079 08 a * .099 10 - .119 12 M .139 14 - .159 Totals Number 172 74 30 17 8 6 1 1 309 Percentage 55.7 24.0 9.7 5.5 2.6 1.9 0.3 0.3 10 0 Mean 0.027 0.001 S.D. 0.025". KF 0014487 Table XI Distribution of Twenty-Four Hour Samples of Faeces to Lead! Content Milligrams of Lead Found In 24 h r s . . Humber Percentage H 0 1 t* oo CM . 0 - .049 .05 - .099 .149 .15 - .199 .249 .25 - .299 .30 - .349 .35 - .399 .449 .45 - .499 .50 - .549 .78 .82 Totals 46 62 79 58 33 15 18 5 2 4 2 1* 1* ' 326 14.1 19.0 24.2 17.8 10 . 2 4.6 5.5 1. 6 .6 1. 2 0 .6 0.3 0.3 10 0 Mean - 0.151 i 4004 S.D. 0 . 10 0 * These two aberrant results are not included In the calculation of the mean value. Kf 0014488 Table XII Comparison of Mean Dally Lead Ingestion with Mean Dally Lead Excretion Mean Dally Intake of Lead Mean Dally Excretion of Lead: In Urine 0.027 . 0 0 1 In Faeces 0.151 t .004 Mean Dally Excretion of Lead (Arrived at by calcula tion from the actual data of combined uri nary and faecal excre tion from day to day.) 0.147 .006 0.178 0.172 .004 tfE 0014489 If the facts are examined in still another manner the same conclusions are evident. Thus if the periods of experimen tal administration of lead are eliminated, the subject- excreted 48.95 mg. of lead In the faeces, and 6.00 mg. of lead in the urine, a total output of 54.95 mgs., in 329 days. During a period of approximately one third of this time (105 days) over which food analyses were made, he Ingested approximately 15 mgs. of lead In his food. It is difficult to escape the conclusion that substan tially the entire lead interchange of the subject Is to be explained by the occurrence of lead In his food. Certainly there can be no other factor of any important magnitude, though undoubtedly some small amount was contributed by drinking water and by other occasional contacts with lead. Prom this it follows that lead was not accumulating in the tissues except for short periods. Thus periods in which excretion exceeded intake alternated with periods in which excretion was less than intake, these effects being brought about by variations in activity, in water intake, In diet, - In short by a number of conditions well within the limits of normal physiological behavior. jj 5 ^ I'.--.-, K & 0014490 iv>*-^Afit^ /*4> *2 ` o; i jftk&ppfoj 4 $ w d S ^ . f :^ 4 J U j I - ' O' : V -'A'i V,;/ d J.7. ^ o T x r ]l 1O.-4' T" "ij Ska& i'c<c-.,J,y ... O.-Q.C4`?..| ,/?.-? 1 IT. ISo. ji IS . lf> i /.r 'J.2 || j ZS.T 7 2.3 .*0,2 :: - . i . ' ' + * . i w . V ' .j - V v - ' i"*jkjMtW&rK & & J r * ? ,': .' . ,, .^k)-4 Cemln'm3.`i-v" |t.Je -, if j 43 iaot \. 7 M ?... i ...53 -;' "i'4 ' 77 . :v4- ;;.v & w ,, i . ? .:. u 7A7 1 ,:` -id `4 . :) l . i a h ,t n j. p ,. ...l.ssj.j (o.%\. !.7 7 . m ijjiA-J 3 8 ... ij'sl 12 . 0 .M-.0...34 ;| * ' *i .....^3^:0.'.5^7 . 0,^-0,4 tf. . i 0.9 j 0 1 0 4 |, A H. r.12 l* .1 . 1 9 . 1 Ji- . c.q 3 .. 1 i.2 ;: ; .. ' I d o .3 ;o [:.. 4 . .L z 1 3 .. o ,9 / -1 .- . . . i f ....:.. 14 Li O''.J#Vr^ \ ~ (V\V.* ' .- i /' '/., i r> .a / ^ i ''/ //.t,.V. ./ i'f /' o-7V `.l f V* : jI J^ sUw 4tt 3,5 4 % .! i .$dl .. : 0.q . 0.Q : / ....0.7/ : ;.,:i| ;- i'`.it ra (10 ;, 1 <A<D5<,23 >-3 :` ..7O | P-^ ..{;. .. ; i . [ , ' d,. -iT, Ij / ./-id 0.<J_1 .,..|.. -......5*',i -2 1.70,0 : d. . . . . . !.... loao;,!lIS I jr [ioo.o'': :i / j.J,3 .. d3L}ioo,o ;a7 t.J?;.A > .. VI.,.:'iYL-.'-ii.... ; ... ;;;_ .0 0 / 3 7 ? ,/:wj :;L 7 _.t.ii''3Of.i.,VfiitOj1 j.*- ...O..i5T .. c, i (^s i 0, oog... iJza.co'i.. j!i1j;i': ji . y. 0,33?, :...0,11 S.. i,l1!!. .P 'i 1 to, || ~o. 7 '. 0 ,1.1 ?, T L*o!.r I :i*<V"i ,.. r ; .-, f. r. - i* fi' Ov i ..,* ^ a jii.efi. f P O ' O - ^ - J i J*" ^ <3.^*7, v>*r!.a. , # r> id {/^0 i~d-- ', X 3. Lead Excretion In Various Groups of Normal Subjects. Prolonged daily observations on u mlngliii subject** yield information as to the variations in lead excretion attend ant upon the changing circumstances in the life and activities of a single individuals, A study of random samples of excreta from a large segment of the population might be expected to demonstrate a somewhat wider range of variability not only as the consequence of greater variation In environment and activity, but also because of differences In the physiological attributes of different individuals# Thus the investigation^of a large and representative group of persons who experience no occupational j exposure to lead compounds, Jby the method of random sampling, should present a fairly adequate cross-sectional picture of the . lead excretion of normal man under present conditions. Incident ally one may determine thereby, whether or not dshe ' who has been studied in detail the average type of normal individual. Several groups of subjects have been studied in the above manner. Medical students, with no previous occupational exposure to lead compounds, form the background for fixing the status of the one subject previously discussed. A number of persons selected from a much larger group of workmen because of v their complete freedom from occupational lead exposure, constitutes an additional normal group,, still another group is made up of workmen with no lead exposure at the time of observations, but Kk 0014493 Table XIII Distribution of Subjects According to Milligrams of Lead per Gram of Ash In the Faeces Medical Students with Ho Lead Exposure at Any Time Humber Percentage Other Persons with Ho Lead Exposure at Any Time Humber Percentage Persons v/ith Questionable or Slight Exposure In an Earlier Period I Number Percentage 0 - 0.029 0.03 - 0.059 0.06 - 0.039 0.09 * 0.119 0 . 12 - 0.149 0.15 m 0.179 0.1S - 0.209 0 . 2 1 - 0.239 0.24 mm 0.269 0.27 - 0.299 0.30 - 0.329 0.33 - 0.359 0.36 - 0.3Q 0.39 0.419 over 0.42 Totals 15 34.1 9 20.4 8 18.2 6 13.6 2 4.5 1 2.3 1 2.3 1 2.3 1* 2.3 44 100.00 4 8.7 10 21.7 13 28.3 7 15.2 5 10.9 1 2.2 2 4.3 1 2.2 1 2 -if 46 2.2 4.3 10 0 . 0 0 2 1 29.6 16 2 2 . 6 13 18.3 8 11.3 5 7.0 5 7.0 1 1.4 1 1* 71 1.4 1.4 10 0 . 0 0 Mean Probable Error Standard Dev. 0.06*}!' 0007 0,071; . : 0.098: *0.008 0 .0 ^ 0 0.072 *0.005 0.06$:: r.~ T i " ' ", ` " L a *. Table (3) ; ' v ' 1 Distribution of Subjects According to Milligr ams of Lead per Liter of Urine iJh'{tjJb.yuAUA *f ' o 2? Medical Students Other Persons with No Lead Expo- with No Lead Expo sure at Any Time sure at Any time Number Percentage Number Percentage Persons with Questionable or Slight Exposure in an Earlier Period Number Percentage CM t-i . o 0 - 0.029 0.03 - 0.059 0.06 - 0.039 0.09 0.119 - 0.149 0.15 - 0.179 0.18 - 0.209 0 . 2 1 0.239 0.24 - 0.269 0.27 mm 0.299 0.30 - 0.329 0.33 - 0.359 0.36 - 0.389 0.39 - 0.419 0.42 Totals 9 20.4 14 31.8 9 20.4 8 18.2 1 2.3 1 2,3 1 2.3 1 - 2.3 44 10 0 . 0 0 7 15.9 8 11.3 11 25.0 24 33.8 11 25.0 22 31.0 5 11.4 6 8.5 3 6.8 2 2.8 1 2.3 3 4.2 3 6.8 2 2.8 3* 44 6 .8 100.0 4# 5.6 71 100.00 Mean Probable Error Standard Dev. 0 .067 +0 .005* 0 047 0.07' +0.005; kO.OSO @069 4,0 * 0 0 o 0.041' ^Excluded in calculation of mean with an occupational history which did not permit of the certain exclusion of slight exposure at some previous time. The excre tion of lead in the faeces and urines of these groups, and the calculated mean values for these factors, are presented in Tables XIII and XIV. The three groups of subjects are so nearly Identical as to be indistinguishable by any statistical means. On the other hand the medical student who was the subject of the prolonged study does not fit into any one of them, statistically, since there Is a significant difference between his mean lead excretion and that of each of them. This ^brings) us-to .recognize the Im portance of the somewhat limited diet of the subject in question. As a matter of choice and habit, this student ate somewhat sparing- a -j cl l y , ,and. Introduced little (variety into his choice of food, i^Thle-. LirCi-ti t-L. 'caused) his lead intake (to be) less than that of the average person. t il r A further difference, affecting only the mean urinary excretion of lead, has been previously pointed out, in that the analytical error was somewhat enhanced by the smaller size of the urinary samples. It is clear, therefore, that although more detailed and specific information was obtained in the study of the one sub ject, a more accurate measure of general experience, as regards lead absorption and lead excretion, is to be found in the observa tions made on the larger number of subjects. Thus the mean lead excretion of normal persons in the United States, with no occupa tional exposure to lead compounds, Is seen to be of the general magnitude of 0.07 milligrams per liter of urine, and 0.07 to 0.09 milligrams per gram ash of faeces. If the average urinary excre- SP arded as approximately two liters per day, and if* the 7 1 is expressed in terms of the mean daily output V s e a TlUt) X.VU the average normal American excretes approximately rd of a milligram of lead per day. ;ad as a Contaminant of Food and Drink. x ,ClOA L he presence of lead in the normal food supply(*equ3hreg-- consideration of many possible sources for its origin. In to leave as little as possible to conjecture, large samples igle common food materials woes collected pv^r*-aMihree~*weks .u!u<!<Ai'1 jLt-A el in the course of ttaa obtv>rwatjro m ?'on tho-modlottl atudbnt tprtwifffea^-wi dn-- . The results of su efo analyses, are JSC A .ated in Tablei-XV, in which the actual weight of food examined, the actual amounts of lead found are given as a basis for the ulation of the concentrations of lead. The data are largely ___ -explanatory, but certain matters merit further discussion. !`{1) Lead is found in all ,fctee-food materials studied,(without j ` ' w:>, regard forj the variety or complexity of the processes of prepara tion and distribution. (2) The quantity of lead in articles derived from grain and in dlCuThUi.. most meats is quite small and would not be found except for delicate methods of analysis carried out on large quantities of material. The''TmtPrnKr-TP!hmJPa*eaace'''t)3r>hymfr>d^^