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Preface .v r Chapter I Introduction Chapter II He thods 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 Compound Lead Absorption and Lead Excretion in the Lead Trades Chapter VI An A^raisal 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 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 ymtfa 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 formsi 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-bearing materials have developed at a more rapid pace, involving'an flosoe increas ing number of occupations and persons in the hazards of lead exposure. Indeed, the number of generally distributed commodities which contain q-uantity.o# 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 K'E 0014430 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 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 v/ho are interested. However, one phase of our work has 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 conditions established by its use. Kehoe and Edgarv carried out the first observations of this type in 1924-25. Late in .2/ 1926, J. P. Leaked and his associates in the United States 0014431 Public Health Service, following a program outlined by a commitel teeAappointed by the Surgeon General, investigated the matter further and extended the number and type of subjects observed. This laboratory fiBB made three further studies, in the winter months of 1926-2*3^ 1927-28v^ and 1929-30 respectively, the first two having been made the subject of detailed reports to the i-MicidL United States Public Health Service, and to tne inaustry in volved. None of the data have been put into such form as to be generally available. The primary purpose of these investigations could not be served by attempting to detect evidences of lead in toxication in exposed persons. Rather, it seemed imperative to anticipate such developments by determining whether 'si-tsO '" -"i whleh might eventually^S^nduce lead intoxication. KA w , .-,A ) / jr kL r ' j f //WJ ' * i's f^:-T c ong tanlKrclatoiohship Utftween tlJ^1 fl\Le"0'P> aba or m apt \S ~ ' itionr -or. Uetlvden tn4 Uiuuunt in-the tioouos ant tto-rntfl , n.f nrrrirM-ffn. nnl.ytlirnl. nfaftariyntH nrn on Ithn _M|. ------ -| i - . t ')U*vu*evc*Xt bland mljJitP'IniHrnrr T'nn'nin'nmynf absorbed1 'SWfid. Jr, it- might be,, that some 1 w^^ekhrngaaLjmt r-BUB.6ptlb3re-o--e-lini< Vi-A.W eal observation (Wwalar be found to vary with the magnitude of lead absorption, as for example, the microscopic changes in .the (SCs blood. Lacking Information on these points Tsmp&rtXT i<r 0014432 -suLiu ftoooffla ary to combine clinical W l o w iu UJHj u s uX1 aiuJJtlSBBffi Varied groups of subjects with, known and unknown exposure o lead compounds. In short, nothing less than a comprehen sive examination of 'iStKSBSSSBSBBBSSSBBHm^ the physiological subject of Investigation. several years :i have been devoted to such ef- forts^ : :-a demonstrated that the normal individual in the United States, experiencing no industrial exposure to lead compounds. Is excretsu^f measurable quantities of lead in both the faeces and.urine. The first observations Indicative of this *swere reported by Kehoe, Edgar, Thamann and SandersY The facts as to faecal excretion were verified by Leake^ and his associates shortly afterward. They have been established LAj>- by the extension of our observations to several groups of a/ carefully selected normal subjects^. Francis and his associ CO ates, as well as Millel^have CO the existence of a similar 'M fnnf 1 nn in England. Vnr^nci,..jT^rmpn V? .8/ .9/ 1CL-o Eadham and Tayloir, Cooksey and Walton , and Tannahill^^, o have obtained like results in Australia, while Fretwurst and L^-C*J /uiy-^ ^ Hertz'xTbave reported similar findings in Germany We^, as X -i well as others^, 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- industrialized 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 f^-frraotthgfin any wry ?y>nm. 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 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 an insignificant 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 &J orest, as follows: 1. What are the sources of the lead absorbed by the average normal man in the modern American community? KET 0014434 J*vJJLj^-iteu^, 3* Are., the-^o the result of modern industry and .4 'Jt commerce, or aj3toihey> tij u j l li*A~*t !fTTSTrnivai flPffgs* condi tion^ of life on a lead-bearing planet, or are both factors active? 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? bx&J~C&i. CXstuAsa.iL&i}- 1~Pl T The mothoda which have been employed ^ and -feho re sults which have been obtained in answer to these questions, are dealt with In the chapters which follow. 7&J nd&J -4 3a L ^ ^^ cj,\i-*yj /),(CC<ixJ ^Zt" ^*ZtsJ tt-f ;?ZLdJt^ Z-h h JL**** Cuj&v-^-o '-4i QsC a^-r|"1 .xsi. 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/ Leake, J. P. and others: The Use of Tetraethyl Lead Gasoline In its Relation to Public Health. U.S. Public Health Bulletin No. 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. Kehoe, Robert A.} Edgar, Grahami Thamann, Frederick; and Sanders, Lester; The Excretion of Lead by Normal Per sons. J. Am. Med. Assn., 87; 2081, (1926) 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, Sy.' 12-S^ December 1929. Tm. fyc-wttMt </ ui Millet, Horace:^J. Biol. Chem., 83:265, (1929) Badham, Charles* and Taylor, H# B.: Studies in Industrial Hygiene, No. 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. 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., _kvt u Quantitative Deter mination of LTTad in Faeces and Urine and Its Signifi cance in Making a Diagnosis of Lead Poisoning, ArchXriyg., 1J.0W4X ;i 15, (1930). --, f 'At *y ' 'N '-'.v fc*---v* IZ Kehoe, Robert A., narnrd^ TTVhaiommafinnnn,. Fredericr>kV ; fTPhVieA TE>x1ycnr.TetiHoftnn noff Lead, J. Am. Med. Assn. 92; 1418, (1929). Leake, J. P. and others; Loc. cit. Badham, Charles, and Taylor, It. B.: Loc. tit. Taylor, H. B.: The Determination of Minute Quantities of Metals in Biological Material Part 1; J. Proc. Roy. Soc. Hew South Wales, 61: 315 (1927). ) Francis, A. G.*p!inaT"Report of DepfciW ' Com. on Ethyl Petrol, Ministry of Health, Great Britain. (1930) Tannahill, R. W. Loc. cit. / Chapter IV The Absorption and Excretion of Lead In Primitive Life 1/ No information available as to the natural presence of 1/ lead In human tissues. Nor W it possible to determine whether or not some quantity of lead la to be regarded as a normal consti- 1/ tuent of the animal organism if observations confined to in- dustrialized parts of the earth. On the other hand, it would' seem that there should be places that have escaped the commercial devel- / y/ opments of present day civilization, and && which the opportunities \/ 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: tx (1) -^The conditions of life must be such as to exclude the possibility of occupational exposure to lead compounds at.any time; ^0 -^here 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 usu-juu. -Jfcpjfc UAfe of canned goods, metal containers and cooking utensils, piped water supplies, and machinery of any kind was 4JW,llSWlll,ilij- f (3) proximity to cities, or easy transportation facilities to and from highly organized communities constituted a further objection; K 0014437 t ' ^ning and smelting activities, with special reference to leadcontaining ores, must not be carried on within such a distance as might provide opportunity for contamination of vegetation, surface soil or water supply ^e^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; & 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. \ V ft'V Persons who-a-aa familiar with MexicQi oeono-will / // recognize how easily many parts of that amazing country meet these requirements^ but~~te-eur-^inchi llie""C0Trdl'trii57r5^^eTQ^^6" c ting 'St ep to^rousq-considerable'^dbub^a's^^^^ k-vl iK*4 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 de-k&iled examin^J^fcon ~e- several 9 such villages andjafterjestablishing mutually friendly relationships \ with the native Mexicans, our doubts were dispelled* awfr Ex 1 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, some description of these two villages and of life within them is necessary. --'*'7* Pueblo de Cachi a small village of about one hundred milies, situated on the Mexican plateau^ thirty-one kilometers \ KE 0014438 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^,C^The adobe houses were xjaady--f:or---theHiarvest, so^.-that-onlT'^bywstandihg"6h'''a^hi^bek^wul^ther ofbe^ee-en scattered, at irregular intervals in the o &** *.'] Or&Jl, midst of the a&ffiattcwi field of <gMk* From-such'a ventage point one~H could see -the- church tower and the- tile~roofe-of-Ixtlahuaca to the^dast, and at a distance of about five kilometers, while to the north^he small f^n__pf._.J.o.c.o.titlan-was~just- recognizable as a series of-white and red -- specks-.. To--th-e'-south',"and' within two-kilometers were -the-white chapel" arid the rambling walls of a oomewhet dilapidated hacienda. AVithin-the cornfields of-the village one came upon a tortuous dlt.ch,._in..whlch..a.plentiful supply of turbid water was flowing, since it Was--the - rainy 'season. . A'-well-worn---path-followed-.the..,sma-U.-~Ganal-and..led tojhe_hpus0Slfc...alX, of. which,...wexe situated-so -as'-to be" conveniently "sUp-"" ^iis^^idh^water 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, 05 provided the means of drawing the water. Bo-th--men~and~women.~wo.rlced_.in.. co the -f-ields''bu`t''sbme' o'f'''the-women...wer.e._tp. be. se.e.n.washing-clothing.-or o woQl_._in_.the- stream-~cadding-*-wool, spinning...thread on . crude spmales. or-- o ~rf / weaving cloth on--simple..looms tied-to-the rooitree~of the -nouse. tana11-- Ux X ^.chilji.ren.j_.jiuiaer.o.u.s....d.ogs , - and - an occasional^-^maIl--plg--tlod by the 'hind leg %c> n,_ nj-.i-rfaft oijpupied--the--dorryafd The--singl-e-room"hcuses'~b'Uilt' of-adobe-blocks, with one door and perhaps another opening for light contained no furniture. Rush mats were on the floor or hanging on pegs on the wall./ These took the place of tables, chairs andbeds. 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 culinary equipment. The occupation.of the men was purely agricultural and pastoral. r.. The only metal implements found in the entire pueblo consist*.ed of sickles and machetes, these.-.latter'"serving-tne--.peaaefuh,,,,pur-po.se-S-_.of--.husbandry. There was no game and no hunting, furthermore, the inhabitants 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. Cachi was poor. Its people had poor clothing and few belong ings. Nevertheless it was essentially self-sufficient. The people / r'\i produced their own food out-of-the-i-r-awn 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 provided freedom from excessive heat and tropical insects, but the warm bright days permitted the growth of vegetation the year r::und. Thus there was no hunger. Such food as was not required in the village was sold or bartered for rime, cloth, pottery, mats, sombreros, serapes, and rebosos. in general, however, very little was produced in excess. Thus only necessities were procurable, and though tobacco fcfcfe relished greatly its use was infrequent. Pulque, the fermented land commonly pu-toeXied-j juice oi one almost ubiquitous magey, was easily available, and was generally used as a beverage by the men and boys. There were no highways between Cachi ana the towns in the vicin- ity. ln-XacJhi^here were^.n-Q^ecogni-zabl^--road-B---i-ntQ^.lxtxn.h.uaca. TTtr~was- HE 0014440 usually necessarv^to walk or to ride on a burro or horse to readx.it* -Xn fliitomobile flftToaA o--qttwtrronable outctnm*"> y wn cr.ur^^l-orea--at--axtabuacair"''t:hg-or!-ly^-pfiyei- *> i cm in ""1*v*'ryXs5Tst.anft ft on h drove u b to Cacni,..showing an.-astonishing skill in' goxng-aro und,over ana througn pools of water ana mua.in.the-open plain, t fte--gr-ea-ter-numberof nis medical vi ait,a Duta-Ld^-.Ixt.iamiaca~aTe~Tna'de~~on 'noTsebaQk. Through the greater part ol.__t.ne year the _ automob.il..e,, ia_.a^.mar3c-o.f-diatlwetTorf,' rather than an article_oi'..-iitili*y - The Indians walked or trotted, often carrying-a-load..oi- sticks or-otiier' material-"-several "time-Ef' their' owiT'buik* i^.e_.o.iuy--xiorse -in tne -village, was.-tne property.,.,pi.,. tne-cniei ihe visits the Xnaians to tne^^nexghhari-ag towns were limited to market aay, ana local or general fiesta days./ The--fbraiefr, whxeh occurred onee..a w.eek-,--provxa'ed` an 'opportunity-for '-seemg-and-perhaps. purchasing- or-trading f or articles from the city* - irL..Ixtlahuaca merchants irom_.Toluca--spread their waresm open-booths along the- streets, while peopl.e..from the countryside -piled their products around tnem on the ground .and offered them for sale-or.^.trade Hwever,-the pervading atmos phere was not that oi a market place but rather that ox 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, in whicn. commercial--- matters were mere incidents. More distant places were visited rarely. Only one of the persons used as subjects m Cachi, an uld man of seventy, had ever been in Mexico uity. ne naa traveled the entire distance on loot, dun-ng--t-he-^elebr^rfc-i-cn hf--.tbe-fiesta"-of->-tne~~virgiH-ox- tiaudilupe The Rancheria el Colera is a small pueblo near Capulhuac about twenty-four kilometers southeast of Toluca and approximately fifty kilo meters from Cachi. Its people and its community life were so similar 0014441 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. i0014442 n o !'C'ZK&f&t' sorvation 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 antiquity 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. V v Fifty-three subjects in Cachi, 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 Dare's instrument, a urinalysis, and blood smears, were made on each subject. Fifty cubic centi C) meter samples of blood for analysis were obtained from thirty- four subjects in Cachi. 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 the purpose. After each sample the syringe was washed out with well watei^, 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. KEf 0014443 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 jars 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* ThiB 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, the 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 make composite samples. The food samples were collected directly into the jars. Upon the completion of the work, each sample was treated 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. fgsq.. uf..cub luma-- 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 village until-they arrived in the laboratory. f Cincinnati laboratory for analysis. Through the /Courtesy of // customs officials it was possible to have them ^elivered to the analytical laboratory without breaking the/seal on a single container,/the customs inspection having been made in Cincinnati in' the presence of a member of the laboratory staff. Thus no opportunity was given for ihe contamination j / of any of the materials from the time they left the Mexican / village until they arrived in the laboratory*---------"711/ " , , . Tables rfyy. to -wdffiC inclusive^ pruseut l/vi ilula rLho.^-^ojt^Ma^ Soil samples taken at random in the fields under cultivation (Table Xvl) 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 may be expected to be found. Similarly, the water contains minute traces of lead. Table XV5rI shows that the vegetation absorbed small amounts of lead.'' ` In the case of prepared foods (Table XBt) it is necessary to consider the opportunities for the introduction 5 of lead from the use of pottery. Table XVIII demonstrates the load-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* K 001.444') %>-- Table XVI Lead in Soil and Water Article i1 ' CACHI , . | COLERO~ ! WM Pound j I/5&d Pound ! O.uantltyi Mgs. | <*//<,<> , Quantity] Mgs. ii Ii -------------j i j. Well "*ater (drinking) 1 3600 c c ? ( Water from Stream(washing); 1 3240 c.c. 0.03 0.00 Soil n. \ ; S <U0 r. zi Soil i;2 Soil ,3 ;r i ,, -i 6-,^ O.lt o.ooj/Lj 3900 CC; 0.00 3860 cc I.C 0 i'.iu j: -j j . " (. ! 1 | 1 0.03 0.03 /> , ^ 0 0 o3 0.Q09# 0.009it /. SC, C 0 o fo Table XVII Natural Lead In Vegetation Used as Food Materials Articles Wheat (dry) Wheat (green) Corn (dry Corn (green) #1 Corn (green) ^2 Corn Stalk (green) #1 Corn Stalk (green) #2 Corn Husks (green) Peas (green) Pea Pods (green) Keans (dry) Beans (Haba) (dry) Beans (Haba) (green) Pods (Haba) (green) Leaves (Haba) (green) Pears (green) Apples (green) Peaches (green) Nopal #1 Nopal 2 Squash (green) Squash Plant Radishes Turnip Leaves Peppers Greens #1 C-reens #2 Capulin (type of cherry) CACHI Weight ' Pb.Found PhT^'Q in Gms. Mss* bvYjjzk' COLERO Weight Pb.Found Pt^Orr \ * in Gms Mgs 99. 40 146. 40 330..70 161..20 217 .00 ; 183 .20 ; i 215 .00 ' | 227 .20 ' ; 273 00 : 116 00 : 175 .00 133 .30 249 .50 : 243 .70 149 .30 214 .40 121 .00 0.04 0.04 0.11 0.05 0.03 0.02 0.01 0.06 0.11 0.03 0.00 0.00 0.03 0.02 0.00 0.01 0.04 p ' ] 85 .70 0.00 ti oJw o.i? o.sr o. o.tf '0.0JO.tttt 0 .M o.m 0.00 0.00 o.n 0.05 0.00 o.or- o-53 0.00 t i 1 * :331.80 ! : 275.00 5i ' i S 291.20 ; !193.00 i 175.40 213.30 , i256.50 j 283.80 ! : 218.10 \i : 262.80 231.10 : 128.60 i 1 335.60 j 71.20 54.80 221.50 32.00 224.60 ; 80.70 i 215.90 | 0.01 0.02 . 0.03o.O? 0.01 0.0J- 0.01 " -9$0.07 "0.40 0.03 0.04 0.74- o.42r 0.01 0.04. 0.04 0. f.g 0.01 0.01 0.03 0.01 0.02 0.01 0.00 0.03 0.01 0.00 0.01 0.02^. 0.0%- 0.23 0.03- o.2 o.p* 0.00 .w o.6r- 0.00 o.oy- 0014447 Table XVIII f Lead In Pottery Used by Subjects Sample CACRI Weight in Gms. Pound Mgs. Percent COLERO Weight in Gms. Pound Mgs. Percent Glazed Dish Glazed Dish Unglazed Dish 1.00 8.20 0.82 1.00 1.00 1.00 13.00 12.50 0.10 1.30 1.25 0.01 0014448 Table XXX & Lead in Animal Products and Prepared Pood Materials Articles Atole -(barley-corn juolj Com In Lime Solution Corn ground for Tortillas Bread Tortillas Tamales (corn) Chicken Eggs - Hen and Turkey Boiled Pork Pork Sausage >Lay|& (pork) Beef Chili (with meat) Cheese Dried Pish Fresh Fish Ajolotes (lizard) Craw Fish Common Salt Candy (local type) pulque Aguamiel Wine CACHI COLERO Weight Pb.Found PV)^%U'43 Weight Pb.Found Fb/AlQ'^s in Gins. Mgs. in Gms. Mgs. 417.50 445.00 0.00 0.04 0.00 O.oi 409.70 544.00 1.70 0.10 oM 117.20 0.02 0.{$ 265.70 0.03 o.f i 73.70 0.07 >45" 119.40 0.07 o.?> 224.80 0.08 o4ur 283.30 0.01 0.04- 419.80. 0.00 0.00 503.40 0.00 0.00 471.50 0.01 0.0% 411.70 0.03 o.of. 492.10 0.00 0.00 73.80 0.02 0.4? 54.70 0.00 0.00 0 gr 1 121.80 0.02 324.40 0.15 O.^fe 84.40 0.00 0.00 26.50 0.04 1>.fc 80.90 0.02 0.24- 207.80 0.02 0 4X5 186.90 0.14 o.fS 204.60 0.21 p.aZ 277.60 0.08 o.l& 3300 cc 0.14 0.04,$Jk Sample Lost 3760 cc 0.06 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 pulcue which probably took up some of its lead from earthenware vessels, and the atole, one sample of which 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 / & > ~y / ) 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 estiras-tfoon, 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 was made. This same process was employed in checking the quantities of lead In all other types of samples, the results appearing In Table X^IV. Thus, despite the 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 UP' 00144b 0 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. Jy.-VIA, J-ii'S.-Oy'-1 &YAj &x }, AI -1' iJIviX'v L{ Table XJCI JfrJ b,Cu. Distribution of Subjects According to Amounts of Lead he Urine CO'.'BITTED GROUPS CACITI COLERO -or- 'pw Liter of Urine number Percentage number Percentage Number Percentage 0 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 4 4.9 2 4.8 2 5.1 3 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 (f>:r>h 10 u' v1 y^-j Standard Dev+*k. Jo. 012 0. ooc% +0.0105 lo. 01^8 o,. ooiz. 0.0114 JoToE37 \to.oo\o 0.0095 * These include two composite samples made up of the urines of two groups of children. Omitted in calculation of mean. KF 0014452 Distribution of Subjects According to Milligrams of Lead per Gram Ash of Faeces COT/EIHFD g r o u p s CACHI COLERO fj * <i Humber Percentage Number Percentage Humber Percentage b 0 1 0.019 28 36.9 0.020 - 0.039 21 27.6 0.040 - 0.059 13 17.1 0.060 - 0.079 5 6.6 0.080 - 0.099 4 5.3 0.100 * 0.119 0.120 - 0.139 2 2.6 14 16 0.18 - 0.199 . i 1.3 20 22 24 0.26 - 0.279 0.28 - 0.299 i 1.3 a' 1 1.3 19 9 6 4 o JQr~ -0- 47.5 22.5 15.0 10.0 5.0 &ve~ 9 12 7 1 2 2 ^rh--* 1 drd 1 1 25.0 33.3 19.5 2.8 5.5 dr'**-' 5.5 2.8 2.8 2.8 Totals Kean s 7"d ..... -...........- 76 100.0 JoToSS? 41 U i +10.0280 40 100.0 36 100.0 IU UOv-)p 0 rwgfr- ;0.039, '0. Wo. oosy +0.0243 .......... 0.0312 ^Omitted in calculation of the mean tfF 0014453 Table XXIII Distribution of Subjects According to Lead Found In Faeces ^M^*?** I ' _... COt,-BINED GROUPS ) CACHI ) COLERO dumber Percentage / Number Percentagetlj^ ........................................................................................ 0 ' ix 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 0.140 - 0.159 0.160 - 0.179 0.180 - 0.199 0.200 - 0.219 0.220 - 0.239 0.240 - 0.259 0.260 - 0.279 0.280 - 0.299 0.30 - C1.319 0.40 - c1.439 1.00 - 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 2.3 3 4.0 2 o lO 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 76 100.0 40 100.0 36 100.0 ttfean 0, 2 oSy 0.0741 0. oo 77 0.0725 fe.130 O-.-0083-- 0' 0 0^3 0.0700 # Omitted in calculation of the means K 0014454 Table XXIV to Summation of Analytical Results as Compared to Amounts Obtained by Composite Analyses Description CACHI CGLERO Sum of :j Sum of Clumber Individ- Number Individ of ual Composite} of ual Composite Samples Findings Analysis:!Samples Findings Analysis filood^Samples -/Pos. 5* . BfeaOfiH&ampSbgs -(I'Jee... 3;:-.. A-Vivwt " Jjrlne--Strmplee - ; Neg. ! 3* foMU4-Postf 12 0.05 0.00 0-78 0.00 1.02 0.08 0.00 0.85 0.00 1.02 32 7 36 1.41 ,.........1.51 0.00 0.00 i . ... 6.15 5.75 Fo-od'"Ssmples Total -f Pos. ! 19 17 i 72 0.97 0.00 2.82 ________ .... ...... ................ i 0.93 | i \ 0.04 ! 34 9 3.17 0.00 2.92 118 10.73 . . ...... 2.97 0.06 10.29 * Material from other samples was discarded*when..Individual analyaA-o -b^-pl an -a^o-. ## Only three negative results were obtained on faecal samples. The `mat-e-r-ia.-l-^vgs1 dlucsn.'ded"bofore-the..adoption 1 of the po-do-oomposih^siiauLyeee. K 0014455 found by analysis was in the blood as withdrawn from the veins of the subjects, for any suspicion that contamination may have occurred is oompjjsbflAy dispelled by the fact that the three samples of residual distilled water from the sterilizer failed to show traces of lead. Table -5&T1 detailing the analytical results obtained on the urinary samples, shows the mean values of the lead ex4 >"u cretion per liter of urine for each group as well as; the 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 magnitude in the two groups of subjects, as shown by the tihd'JJJ meanSfy 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 ash in the faeces, (Table XXII); shows a slightly greater variability, but the two groups of subjects are similar in x this regard, and may not be differentiated statistically.,/ A ^comparison of these mean values with those obtained from the study of the medical student (cf. Tables VlX^and VIII), brings out the surprising fact that they are of the same order of K 0014456 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 lhat 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 midtiigrannr in^ the liexiaan 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 which is ingestdd by the average American is derived from natural sources. A classification of the Mexican subjects on the basis of 1 ' rc. 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 KEF 0014457 Table Distribution of Subjects According to Age ;e 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 Cachi 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 HE 0014458 Table XXVI ; jrt.'.'uV-'-'A 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 j (Number of Subjects as Number of Subjects as Number of Subjectsj Lead Findings ijto Lead Found to Faeces to Lead In Mgs/Gm Ash to Lead to Kgs/L. Urine Milligrams ` jCachi Colero Combined Cachl Colero Combined Cachl Colero Combir :;i?,G - 0*019 2 0.020 - 0*039 2 0*040 - 0.059 ; 4 0.060 - 0.079 / 2 0.080 -0.099 L 1 0.10. - 0.119 0.12 - 0.139 0.14 - 0.159 0.16 - 0.179 0.18 - 0.199 0.20 - 0.219 0.22 - 0.239 0.24- 0.259 0.26 - 0.279 24 1 2 1 1 11 5......... 5............... 10 9* .....12# _ 21# 11 Totals 12 15 27 Means (Combined .k ' /*> S. D. ______ 'J Groups!) 10.0881 ____ :z:::z.xK,^orx +0.0712 12 15 27 foTosSe _o~o6s-- '~0 Zo'bsz 0.0409 * Only six of these are nil, two from Cachl and four from Colero. ^Calculated after a wider distribution of findings. K 0014459 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 Ll-CUA villages are stable. The means are not gbi-fM-Ly 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 to their pueblo. They had spent their entire lives up to that time in the immediate vicinity of $heir native village. The examination of blood smears made from these subjects establishes a fact which is of some consequence in relation to lead absorption. Much discussion has con- /vl IS t/ ceitted 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 -' KF 00I44G0 Table XXVII Distribution of Subjects ae to Stippling of Erythrocytes Number of Stlppledj CACHI COLERO......... 1 Erythrocytes per 1 1----------------------- - 50 Fields = Number Percentage Number 'Percentage i ______ 0, 3......... . . ; 28.... ....... A JJ_... .38 ,, ..!.....9/ .5........ 4- 7 .8 1! 12 - 15 12 ;3 3 ?o-0 sj~ ;. _ { o+*4 i i1 4.3 . l.z 16 - 19 20 - 23 24 - 27 5 ' 1 1 n\ /.7- : 1 LI ^ 28 - 31 32 - 35 36 - 39 40 - 43 44 ** 47 50 - 53 54 - 57 74 * 77 Total 3 1 1 2 .............. 60 o. 0 1.7- !> 7- l> jj n \\ wVIt t, II n a 1; |j 1 3.3 _ /(>D h: >'): 42 ' 2.1 / >''J K 0014461 ' ...... Table XXVIII Distribution of Subjects According to Haemoglobin of Blood Haemoglobin Reading(Dare) CACHI Humber Percentage 65 - 69 70 - 74 75 - 79 80 - 84 85 - 89 90 - 94 95 - 99 100 - Totals P' 3 17 13 15 9 1 1 59 5.1 28.8 22.0 25.4 15.3 1.7 1.7 100. 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 were 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. 0014463 Chapter III The Sources of Lead Absorption In the Modern Community 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 J/ and drink. As 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 prin- . v/ clpal source of lead jUt*!** 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 t'-at of the ninjeenth century, while many other matters of everyday life have seen revolutionary changes. There ? fore it is necessary to examine(thejconditlons 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 variants, 1. Lead Excretion in. Infants and Children. Children were taken at random from various services in a children's hospital, WydL';f_- 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 v/ore also avoided. In so far as it was possible, samples of urine and faeces were col- looted directly into the containersIn 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- j bearing materials. yv Table Jy shows the ages, the gounds for admission to the hospital, and the lead findings in this group of children^ >/ the mean values for the excretion of lead in ^ g 0014465. n..... f>!5i \ .. V>-V rt o3> V'<? f- 080 Jt. 'P0&:?{& 0~,QZ*f 03 -'.oS'q Oi _,<?<?? . W-./t? fZ- /</# /S' 7? /S-/2o<f z Jo <? .6' 3. % / 3r * O i -2 -fe . ^U, 6 ' O% /O' /# /<?/ 2. ;0 ' 4.._ T -.-vX. JH* ' i/ ;s -.<? 0 /h 3&' sJV ^/r ga 3k V31/ / - TY A,OJ + 3V r ,2o3 lor - c^arfovs 3V >3'X co CO ~ k*2> '3 V - V*1^7V ; ~ T* **< r~ o o 0^ _ (21 i* V3<f fO 3c ,47Y-Vq '0V-$9 %30M. -] '<-,' 0,02oa r11 Dmnn 111 f?r -. ,00^0% S./S. - 10.043*1 S.ySoCfSt / P.2. . Y 0.00 Sag Table TJ Lead Excretion in Normal Children Hospital Identifi cation Ho* Description of Case or Diagnosis 0-4 'L tjw* LEAD IN FAECES LEAD IN URINE Mgs Mgs/Gm Found Ash Mgs. Found Mgs./ Liter . 90 245 . 970 V 2130 2330 2504 - 2582 2783 2375 3043 3091 3119 3337 3377 3387 3528 3531 3532 3604 3691 3695 3698 3703 3706 3726 3763 3779 3780 3846 3866 3874 ' 3887 3901 3967 4020 4026 Orthopedic Treatment 9 Chorea 8 Cardiac Lesions 7 Fo-St " 0 j* erctf t v< . 5 Cardiac Lesion 10 Orthopedic Treatment 12 Convalescent Polio- .4 Orthopedic Treatment 4 Convalescent Fracture 4 `Astragalectomy 9 Osteomyelitis 11 Post-appendectomy 7 Eczema 1 Chronic Appendicitis 14 Osteomyelitis 7 Mastoiditis 6 Dietary Regulation 0.6 Oesophageal Stricture 7 Chorea 11 Post-anpendectomy 11 Osteomyelitis 10 Post-appendectomy 12 Anemia (type?) 5 Post-appendectomy 13 Otitis media - nephritis 12 Arthritis 6 Post-appendectomy 12 Convalescent Fracture 12 Alkaptonuria 0.25 Convalescent tonsillectomy 8 Post-appendectomy 11 Convalescentfburn 6 Mastoiditis 15 Chorea 8 Orthopedic Treatment 7 Tonsillectomy 8 0.30 0.27 0.27 0.10 0.38 0.61 0.05 2.22 0.62 0.14 0.42 0.10 0.37 0.09 0.53 0.21 0.26 1.57 0.29 0.45 0.14 0.41 0.43 0.17 0.10 0.23 1.28 0.24 0.23 0.60 0.39 0.24 0.23 0.70 0.90 0.06 0.17 C.09 0.08 0.03 0.11 0.03 0.23 0.10 0.13 0.08 0.20 0.005 0414 0.31 0.11 0.14 0.06 0.07 0.10 0.08 Nil 0.13 0.11 0.07 0.20 0.03 . 0.24 0.06 0.13 0.05 0.18 0.03 0.13 0.19 0.04 0.11 0.37 0.05 0.24 0.01 0.12 0.06 0.17 0.14 0.10 0.22 0.03 0.17 0.01 0.18 0.07 0.13 0.15 ' 0.29 .0.05 0.15 0.15 0.11 0.11 0.20 0.04 0.05 . 0.06 0.03 0.03 0.23 0;11 0.13 0.11 0.09 0.17 0.06 0.09 0.08 0.07 0.08 0.09 0.13 0.07 0.06 Nil 0.08 0.18 0.08 0.07 0.09 0.11 0.02 0.07 0.11 0.07 0.05 0.04 0.08 0.17 0.07 0.04 0.09 0.10 .0.39 0.12 0.03 0.04 0.11 0.12 0.10 ! . . ( <t (.., X/,; 7 W I|r r.f- . ` ^ 1 1 tfg 0014467 O,0$G 1 o>oo~ 1 o. 0 6 o. o$lf o. 5 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. 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 thepung, 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- ^ Cue tion. One of them had been breast-fed from birth. Thus the 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 3 a representative 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 0014468 Table Y Lead Content of Human Milk ubject No. 1 2 3 4 5 Volume of Milk in c.c. Lead Pound in 2031 ! ! 0.05 1936 0.10 2306 0.09 1230 0.04 2853 Nil K" 0014469 4 o subject. All'"of; the subjects were housewives, with entirely negative histories in such matters as occupational exposures Y to lead, recent illnesses, and recent*sources of medication. >/ Table %. 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"tfcy not apply to the present matter except in so far as that lead absorp ' Os. 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. V-' i- "h'-N > * - hA ' .J~ A , -i ;i.' i -f, t 1 ' r\ * :* A -.i, i / 2. Lead Ingestion and Lead Excretion in a Normal Adult. h a healthy medical student v/as selected as a subject for ,v ' 1 VAJ uV ',Ltdaily observations over a long period of time. His understanding of the character of the problem provided the intelligent care / 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. 0014470 H Fig. 1. Lead Excretion in a Normal Subject 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 blbck gives the lead In mgs. per gram of ash In the I: faeces. The dotted line records the average levels of faecal ex- ' cretion of lead for the periods over which it extends. 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. K 0014471 iH i& r m of Lead Fig. 2. Lead Excretion in a Normal Subject The blocks represent consecutive daily observations as an uninterrupted continuation of Fig. 1. 0014472 Three matters- of special note may be seen in Figure 1. ` 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 A higher level than the urinary, and is subject to wider varia tion. It is clear that theye 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 daily custom to take*1^--*rTTTly. A slight brief rise in the urinary excretion of lead coincides with the day of discontinuance of milk. The faecal excretion also, shows an elevation, with irregularly * spaced,very high peaks. That neither of these changes di rectly due to the elimination of milk from the diet will appear later. Then daily vigorous exercise was carried out for three weeks. There is a definite rise in the urinary excretion, with 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 tiers of Urine Pig# 5. 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 0.22 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. 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 mask the effects of other experimental measures. This factor is assoc-ia-ted-wi-th the quan tity and quality of ingested food. It may be noted that the faecal excretion of lead shows wide 7 Footnote: The very high figure obtained on the 124th day is entirely \! unlike any other result obtained during the entire study, and ljencejis probably in error. This figure of 0.14 mg. in 630 c.c. of urir^e repre- > sents a concentration of 0.22 mg. of lead per liter of urine. Such la conc; entration Ii is not/- found in the urines -of norm al sub jects, anpiL/ litldoes \ 1/ * - . k ./ !\ not occur agaip in/this subject, even when lead was adim-flistered for\ \ \j :/ ! \/ *' \/ <, ,i f experimental purposes. It must .be the result/of contamination of the sample at some point in its collection or analysis. Kf 001447b 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 exorcise 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 J- v -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 l^uarts of milk daily which had been an important, item of diet previously# KE 0014476 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 bo 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 low 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, Either of these in- fluences q .m ho to have bean exerted any Important" because of the ovGr*^\AW^*^y gjy&a&ejp effect of the on o.' amounts of 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. W now v/ished to study accurately the influence of administered lead on the rate of excretion. A 0014477 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 oonclusibn 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, v 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 and 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 co 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 tration, while the third marks the end of the time over which the data of the inset table were obtained. The three plateaus 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 weeks supply of each article of food was combined into a single sample for analysis. The total lead found in all such samples was spread evenly over an area which represents the entire week. .1^ Agair.0 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 ftolalmost) 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 daily intake of lead is exceedingly variable.. Indeed so great is the variation that it is impossible to interpret^hanges 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 rT 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 ware 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 wsre 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 Ar, if?; total quantities of lead wane administered, the absolute quantity absorbed would greater 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 urinary excretory rate, yet there no distinct increase in rate over that of the previous period. That is to say -thfrt^the KE- 0014480 f M Mt ii __ L* s I''l-Ecq iU(\"K, M. ill Jt M HZ. M HI Calcium Lactate zg uis. Daily ^jj Mftatioii Ammonium Chloride iz g w . Daily 30 1931 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* t< 0014481 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 the ingested iead remained low during the remainder of the study, furthermore * the urinary excretion of lead was almost negligible during the period represented in these two figurws. xables YXI and VIII show the frequency distribution of the resultB in milligrams per gram of ash in the faeces, and per liter oi urine* together with the calculated means^ for ^these items. Jne,percentage of negative, __the mean' value of lead per liter of urine, is_unhouD.t,,eai.y- due~an"'pahV"to^ the'` r`aet'''that"'the' urine was^ collected in twenty-four hour ^samples* the volumes of which in many instancea-were less than~-one--liter. ..ouch quantities-..obtainedjfrom normal subjects .frequently K'fc 0014482 Table VII Distribution of Urinary Samples g to Lead In Milligrams per Liter Milligrams of Lead Per Liter of Urine Humber Percentage too. .o .o -3 t9 *1 0 - .009 .01 - .019 .02 - .029 .039 .049 .05 - .059 .06 - .069 .079 .089 .09 - .099 .10 - .109 .11 - .119 .22 179 44 33 16 16 7 5 3 1 2 1 2 i* 57.9 14.2 10.7 5.2 4.9 2.4 1.6 1.0 .3 6 .3 .6 .3 oCO Totals 309 100. Mean ~ 0.017 3 0.001 S.D. = 0.003 ^ Omitted In calculation of mean. KT 001 Table VIII Distribution of Faecal Samples afi- to Lead In Milligrams per Oram of Ash Milligrams of Lead ' Per Gram of Ash Humber 0 _ .009 .01 - .019 .02 - .029 .03 _ .039 .04 - .049 . .05 - .059 .06 - .069 .07 - .079 .08 - .089 .09 - .099 .10 - .109 .11 - .119 .13 - 52 95 75 38 27 20 7 3 2 3 2 1 1 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 s 0.027 0.00(2 S.D. = 0.020 KE" 0014484 fail__io^~ahow--amtmfh""~of lead vihich'are-- capabl-e-^1---accurate-quant-i tative o&t4mation* j?'or thls..reasun'--nolr~i'e8S''*tlian^two lTters'lLs-'des-irabl'e'f wr the--purp.o.s_e,,Q.f, each observation in a - 3tuny-ox--tme^normal'excretion of lead ine conaixions of _tiie_l-Qregoing--ohsep^ii^d^ne-"were"d'eTied--wi-th'-a full recognition tnat tne.limitations of'the analytical methods would develap._arLjLncrea9e&. importance in dealing with the samples of urine* Ihxs--mat-ter--is_of- mu-ch-less-signlf jcance--i-n--the--ease--of-the--faecal earn- pte.s_f or,,_thereason..that-i^e-l-arger^u'antities''df'lead'prtrs-erilrxeduce the-proportional analytical error, mrnpattnii-tr^Ty inw value of the mean excretion of lead in milligrams per gram of ash is .ovide-n-o^--1-ewer, ra^eluf-^ead^xeret-ron--than `irs* `weBBtew-iir- normal 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 da 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 IX, 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 i3 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* ' KEf 0014485 Table Djj ttccrulb*^ Distribution of Dally Food Samples -as to Lead Content H O CO Milligrams of Lead Found in 24 Hrs. - a - .049 .05 - .099 - .149 ,15 - .199 ,20 w* .249 .25 - .299 .30 - .349 .35 - .399 .40 - .449 ,45 .499 Totals Number 13 16 > 33 24 9 5 4 0 0 2 105 Percentage 12.4 14.3 31.4 22.8 8.6 3.8 1.9 100' Mean = 0.147 0.006 S.D. 0.086 0014486 Table : Distribution of Twenty-Four Hour Samples of Urine to Lead Content Milligrams of Lead Pound In 24 hrs. 0 - .019 02 - .039 04 - .059 06 - .079 08 - .099 10 - .119 12 - .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 0.3 100 Mean 0.027 * 0.001 S.D. 0.02S K f 0014487 Table XX Distribution of Twenty-Four Hour Samples of Faeces to Lead Content Milligrams of Lead Found In 24 hrs. Number Percentage 1! O CO o >.CM 0 - .049 .05 - .099 .10 - .149 .15 - .199 .249 .25 - .299 .30 - .349 .35 - .399 .449 .45 - .499 .50 - .549 .82 Totals 46 62 79 58 33 15 18 5 2 4 2 i* i* 326 14.1 19.0 24.2 17.8 10.2 4.6 5.5 1.6 .6 1.2 0.6 0.3 0.3 100 Mean - 0.151 * .004 S.D. z 0.100 * These two aberrant results are not Included in the calculation of the mean value# KiT 0014488 Table XII Comparison of Mean Dally Lead Ingestion with Mean Dally Lead Excretion .Mean Daily Intake of Lead Mean Daily Excretion of Lead: In Urine 0.027 .001 In Faeces 0.151 + .004 Mean Daily 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 t .006 0.178 0.172 004 *K 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 64.95 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. K 0014490 ,,> v P o ^ ~*f )) Xf A',';, / W &5*k ,fe-*2 ? .......0 - C.C4'?... ...<?<?-. o-xsq. /.....;... Ht,f.k . j )i .,-:,./ ;>,. ' '/ c.?U '.fi it?/A-'CAfcJt* Jewtl ,v / , 7. '4$ - >v Ml .'! ;;' \/ C(-mhnc2 V?wv,* . ', v 'v;,v" 4 . fix i'T : iso J is '0.S !1l1 441 iso; ,/.':/* \ -u i Xs? j 25.7...; as ' 2-0,3 ... ......... . 2Q..3.; .44 j . S3 ; 20,3 J.; J>( $ i! 77 O.JSr-O.JQ'? ; ' '.'A- .oil f!!. 14 ; ii4 !! :.a. JSo 1..., .......JL 5b MA=J2.XA1.. : i2i.4.5W. .7 ; 7./ ipj 4 4. . n 6 C 2..; '. ...7 j ! ^$9 u.......1 u\. : .........!! ! 38 ills] 3. .5,4:1 .u,3^;Q.-.5'?7 . :. _:1 ' l',: !1l1! i^ .J* ; 1 . . H. 0.9 .; i.1..: X. I..44!;. ,x.. J.2 i; ; 1 II io ,. 3.\o r 4 ...i'4. 0,16-0.4i(..: ,- . ; . Q.9. :! i u: I s ..0.9 0/1,5-0.161 .; ay--- / ? : 11 . r LS\......: I 4 Ida: /*/?.. ...,! :4io (( / *fL1i!; .O2300J.,.c3??<? .,. : % 1 i&i-!]...... ....Hii 1 ; 1, 5 i.% ; .. i ^-33 . ! *! O.q J \ J,-.\..M.. / ' / J.?.:! . - .'. *-.j./ `.w "j . LA *<qS ' V: vi .... 1 ,,4 4- ` ' ' V I -J- io 5 loo.Q loa o:; .1X3 lioaojj S^J yy ! ' ' X A,. / -- ""y J>J'i!KLlASi.___ : . P ! !` l ` V,, 1 ................. ;4 (-( 0 ..... :.... 0,i5.r.... i 0, cog* i,,QJM.. i .40,007 !ri!; U h A. >i.. f .<>, 1 i W-. 0,4 22. :: 0,115 :. Bit Jjloao 0.157 T` ;,o, oo^j.__ 0.113 , . o j '%r -f f | J .* < ?-- C1 / fP l-'w-V/t. A 1 .) V : l<*-0 (1..V-7 -lJ/<,, / , ; <r> V. . ,, -..Jit ft 3{j,-x^sC` ' , . ,(lo^L,t xL&XLi^-u, cii i. X IS ! '. t5 ! f f^ i <* V 's <v V "Si* 1^ '.'4* tv ~Cv So dx sJ JO V \a h 001 4B2 3. Lead Excretion in Various Groups of Normal Subjects. Prolonged daily observations on u m hnglu 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 ; exposure to lead compounds, Joy 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 ' who has been studied in detail represents 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 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 Table XIII Distribution of Subjects According to Milligrams of Lead per Gram of Ash In the Faeces Medical Students with No Lead Expo sure at Any Time Number Percentage Other Persons with No Lead Expo sure at Any Time Number Percentage Persons with Questionable or Slight Exposure in an Earlier Period Number Percentage 0 - 0.029 0.03 - 0.059" 0.06 - 0.039 0.09 - 0.119 0.12 - 0.149 0.15 - 0.179 0.13 - 0.209 0.21 - 0.239 0.24 - 0.269 0.27 - 0.299 0.30 - 0.329 0.33 - 0.359 0.36 - 0.33 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 1* 44 2.3 2.3 100.00 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 2.2 2* 4.3 46 100.00 21 29.6 16 22.6 13 18.3 8 11.3 5 7,0 5 7,0 1 1.4 1 1.4 1* 1.4 71 100.00 Mean Probable Error Standard Dev. 0.06^`r 0.007' 0,071; 0.098: 0.006 0 0$0 0.072 0.005 0.06$:: * Excluded in calculation of mean K? 0014494 r. l Table 6> Distribution of Subjects According to Milligrams of Lead per Liter of Urine A4AU4 fj* Ua, Ua^ML Medical Students with No Lead Expo sure at Any Time Number Percentage Other Persons with No Lead Expo sure at Any time Number Percentage Persons with Questionable or Slight Exposure in an Earlier Period Number Percentage 0 - 0.029 0.03 - 0.059 0.06 - 0.089 0.09 - 0.119 0.12 - 0.149 0.15 - 0.179 0.18 - 0.209 0.21 - 0.239 0.24 - 0.269 0.27 - 0.299 0.30 - 0.329 0.33 - 0.359 0.36 - 0.389 0.39 - 0.419 0.42 Totals 9 14 9 8 1 1 1 1* 44 20.4 ol .8 20.4 18.2 2.3 2.3 2.3 2.3 100.00 7 15.9 11 25.0 11 25.0 5 11.4 3 6.8 1 2.3 3 6.8 3* 6.8 44 100.0 8 11.3 24 33.8 22 31.0 6 8.5 2 2.8 3 4.2 2 2.8 4# 5.6 71 100.00 Mean Probable Error Standard Dev. 0.067' +0.005* 40.047 0.076" +0.005; *o.o$o *069 +0.OOo 40.041 ^Excluded in calculation of mean Kf 0014495 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 o 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, ij*. and introduced little (variety into his choice of food, ^Thie-^ uj iv-Cuit-c* Viav 'caused) his lead intake (to be) less than that of the average person. 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- 0014490 \P the average normal American excretes approximately .rd of a milligram of lead per day. sad as a Contaminant of Pood and Drink. "' JtuiM Tr .`he presence of lead in the normal food supply/roquiree-- `onsideration of many possible sources for its origin. In to leave as little as possible to conjecture, large samples 'h*sr4J i JLK-t<S igle common food materials mse collected ever- a -three1 weeks (1 in the course of tbs obenvn felons1 on tho-medloal studfent The results of -eu^h, analyses, are .ated in TableSXV, 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. J" ^" wl'-:'-!1 ``(1) Lead Is found In all food materials studied,/without; 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 dttmhu^ most meats is quite small and would not be found except for delicate methods of analysis carried out on large quantities of material. is^jjjagenc|a^ixi ^owrn^wveTre'l a' 'the--eaae*-- HE 001 449V