Document MGyMGGxYXp4vom9noR1LMKz8k

Automobile repair shops, 0.13 mg., and in street air, 0.05' mg. to 10 cubic meters. Greenburg ** has reported that 1.45 mg. of lead daily for two and one-half years has caused poisoning. Teleky states that 1 mg. of lead daily for several months and Legge and Goadby 14 state that 2 *Wmingh.i-lieda*tihil-y-e-s-e-fo_f_ri_gs_ue_rve_es_ra_ml *aymyea_as_res_e_mw_i_ltlo c_vaau^rsye lead con- sidcrably, it is true that lead in the form of vapor is re dangerous than as dust, and the circumstances under which the foregoing estimates were determined were not identical. Certainly it may be concluded that a daily dosage of from 1.5 to 2 mg. is distinctly hazard ous and eventually will cause poisoning in most, if not all individuals. In this connection it should be noted that when lead is in a molten condition fumes will be riven off; the higher the temperature, the more fumes; also oxide will form on the surface and get into the air as dust. this view Brooks* agreed, but Maxwell and Bischoff V and recently TCehoe and Thamann * have objected, largely on the basis that lead in .the blood stream reacts more with red blood cells than does the phosphate.- Maxwell and Bischoff * have produced some evidence that lead, when injected intravenously, is carried as a diphosphoglycerate, while Jowett * thinks that it forms a complex inorganic phosphate with calcium and chlo rine. In a chemical system as complicated as blood plasma, an equilibrium of several such chemical com pounds is not unreasonable. Any of these compounds might remain ionized and dispersed in the presence of plasma proteins. But whether it is transported as an inorganic or organic phosphate, it is obvious that lead in the blood stream can exert deleterious effects on body cells. Of course, some absorbed lead is probably excreted (partly in the urine but mostly in the feces) without ever having been stored. There is a growing accumu CO NCLUSIO N lation of data obtained by different chemical technics It may be stated that lead poisoning is very prevalent, that indicate a small daily lead excretion in the urine though "most of it is mild. However, both mild and in the vast majority of the people in this country and occasionally severe cases are commonly not recognized. elsewhere.* The average result of these observations Manv cases are diagnosed as chronic appendicitis and indicates a urinary excretion of lead of from 0.05 to even as gallbladder disease, with all too frequent sur 0.1 mg. daily in individuals with no unusual lead gical intervention. In connection with industrial hygiene exposure. This urinary excretion represents lead that studies, insurance company records show that, with has been actually absorbed, but a large percentage of res|>cct to illnesses of more than seven days' duration the lead found hr the feces has probably never even among wage earners, respiratory diseases greatly out been absorbed. Because of such repeated observations number gastro-intestinal diseases. When the ratio is it must now be agreed that a qualitative demonstration inverted and one is confronted with a situation wherein the gastro-intestinal cases outnumber the respiratory cases, the possibility of lead poisoning should always l>e considered. 5ama t o ^ r - n ^ o . m - r of small quantities of lead in the excreta does not necessarily signify abnormal exposure. According to Barth,789 a very small amount' of lead may even be gradually accumulated in normal bones during advanc ing years (from 0.02 mg. found in infancy to 0.1 mg. THE BIOCHEMICAL BEHAVIOR OF per 3 Gm. of bone ash in the aged). If larger quantities of lead are inhaled, swallowed LEAD IN TH E BODY or injected, excretion does not maintain an equilibrium, JOSEPH C. AUB, M.D. and lead becomes stored. But the extent of possible storage can be ascertained best when a known quantity BOSTON of lead is injected intravenously. Millet,* Kehoe and In the last ten years, a great deal of work has appeared bearing on the biochemistry of lead. To com bine this new knowledge with that summarized in a previous publication *123456is my purpose in this article. In regard to absorption there is little important new evidence. The experience in industry confirms what has been found in the laboratory 1--that lead which is Thamann,' and Aub and Smithwick 10*have shown that but little of this is excreted promptly. For example, the average of six of our cases, studied for forty-six days during the injection period, showed that only 69 mg. of lead was excreted in both the urine and the feces, although 473 mg. of lead as colloidal phosphate was injected intravenously. inhaled is far more toxic than lead which is swallowed. 2. Brooks, John: The Interaction of a Finely D ivided Lead Suspen Of course, it is likewise generally conceded that sion w ith Blood Serum , R inger Solution and A queous Phosphate Solution, Biochem. J . 2 1 : 766, 1927. ingested lead is a hazard. 3. M axwell, L. C.. and Bischoff, F ritz : T he R eaction o f Lead with th e C o n stitu en ts o f the E ry th ro cy tes, J . P h arm aco l. St E x p e r. T h e rap . The form in which lead is transported in the blood 3 7 :4 1 3 (D ec.) 1929. 4. Kehoe, R. A ., and Tham ann, Frederick: T he Behavior of Lead in stream is of practical as well as scientific interest, as the Animal O rganism : I I I . Colloidal Lead Compounds, J . Lab. St Clin. it has a bearing in guiding intelligent therapy. The M ed. 1 9 : 178 (N o v .) 1933. 5. Jow ett, M aurice: The Reaction of Lead Com pounds with Serum prevailing opinion Jiad long been that lead was carried and Serum Models, Biochem. J . 2 6 :2 1 0 8 , 1932. 6. Badham , C., and T aylor. H . B .: Lead Poiaoning, ex tract from the as an albuminate, but Fairhall's equilibrium experi R eport of the D irector-G eneral of P ublic H ealth, New South W ales, for ments,1 as well as our blood studies with Reznikoff,1 th e y ear ended 31 at D ecem ber 1925. K ehoe. R. A .; E d g a r, G ra h a m ; Tham ann, Frederick, and Sanders, Lester: The Excretion of Lead by. convinced us that lead was precipitated in the bones N orm al P ersons, J . A . M. A . 8 7 : 2081 (D ec. 18) 1926. F retw u rst, F .f and H ertz, A .: Q uantitative D eterm ination of Lead in Feces and U rine as the very insoluble tertiary lead phosphate and carried and Its Significance in the Diagnosis of Lead Poisoning, Arch. f. Hyg. 1 0 4 : 215, 1930. Litzner, S., and W eyrauch, F .: U ntersuchungen in the blood as the more soluble di-lead phosphate. To uber den Bleigehalt des Blutes tind H arn s,-se in e Beziehungen rum A u J treten klinisener K rankheitserscheinungen sowie seine diagnostische 22. G reenburg, L . ; Schaye, A . A ., a n d Shlionsky, H .: P u b . H ealth B edeutung, A rch . f. G ew erbepath. u. G ew erbehyg. 4 : 74, 1932. K ehoe, R obert; T ham ann, Frederick, and Cholakr Jacob: On tbe N orm al A bsorp Rep. 4 4 : 1666 (J u ly 12) 1929. tion and Excretion of Lead: I. Lead Absorption and Excretion in P rim i 23. Teleky, L .: A rch. f. G ew erbepath. u . G ew erbehyg. 5 : 132-137, 1933. tiv e L ife, T. In d u s t. H yg. 1 5 : 257 (S e p t.) 1933. 24. Legge an d G oadby: L e ad P oisoning a n d L ead A bso rp tio n , L ondon, Edward A rnold; Now Y ork,t Longm ans G reen & Co., 1912. Read before {he(Section o n Preventive an d In d u strial Medicine and Public H ealth at `.tnS E ig h ty -F ifth A n n u al S ession o f the A m erican Medical A ssociation, C leveland, J u n e 13, 1934. 7. B arth, E .: Investigation o f the Lead C ontent of. H um an "Bones, Virchow s A rch. f. path. A nat. 2 8 1 1 146}.1931. 8. M illet, H .: T he Excretion of Lead in U rine, J. Biol. Chem . 8 8 1 265 (A ug.) 1929. 9. Kehoe, R. A ., and Tham ann, Frederick: T be Behavior of L ta d in the Animal O rganism : I I . Tetra-Ethyl Lead, Am. J . H yg. 1 8 1 478 1. A ub, J . C .t F a irh a ll, L . T .; M inot, A n n e S ., an d Reznikoff, P a u l: (M arch ) 1931; footnote 4. ; ;>" * Lead P oisoning, M edicine M onographs, B altim ore, W illiam s St W ilkine 10. A ub, J . C ., and Sm ithwick, R . H .: Lead T re atm e n t o f C ancer, Company 7 , 1926. New England J . Med. 2 0 8 1 310 (Feb. 9) 1933. <j A- v* LEAD IN THE BODY--AUB Joua-A-M-i Once lead is absorbed, there is a characteristic dis tribution in tissues, which is approximately the same for inorganic,11 organic * or colloidal lead,11 no matter what the route of absorption. It is distributed through out the viscera, but to the greatest extent in the liver, `spleen and kidneys immediately following absorption. After a very few days, however, it gradually collects almost entirely in the bones. It is interesting that even a relatively stable organic compound such as tetra-ethyl lead should behave like other lead compounds (Kehoe) in spite of its great solubility in body lipoids. The crux of the whole problem of lead poisoning, just as for other heavy metals such as radium l* or mercury,*1234*167 lies in the great avidity with which the bones take up these metals. Circulating lead may cause tissue damage, but lead stored in the bones produces no deleterious effects except probable caries in the teeth. The problem of treating lead poisoning is the problem of controlling the deposit and excretion of lead from this skeletal storehouse. It was the original contention o f Aub and Anne M inot1 that the direction of the lead stream is similar to that of the calcium stream--that, when calcium is being deposited in the bones, circulating lead is also deposited in the bones; and, when calcium is being pulled from the bones, some stored lead is also liber ated.1 This rela -1-- 1-- v7/y>Tm -- '-- ; tionship has been extensively investi gated by most labo- rious metabolic observations. The patients received daily the same diet, similarly prepared throughout th e ir low calcium peri ods of observation. Their total excre tions were collected in three-day periods and analyzed for lead by Fairhall's method. The rate of the lead stream could thus be fol lowed. But the magnitude of this lead stream, it must be remembered, is apt to be relatively C hart 1.--The first value indicates the lead excretion as acute lead colic was sub siding during high calcium medication. L ater, the sustained it e a s e in lead excre tion, w hich accom panies a low calcium diet plus am m onium chloride, is well shown. The c h a rt shows th a t the increased excretion is largely fecal. small. An adult dy ing of chronic lead poisoning probably has not more than 1 Gm. of lead stored in the entire body, and nearly all of this is in the skeleton. After removal from exposure, such stored lead is normally but slowly excreted. The charts of a few of our unpub 21. A ub, F airhall, M inot and Reraikoff.1 W eyrauch, F .: D istribution of Lead in the O rganism K fter Intravenous Injections, Ztschr. f. d. ges. ex p e r. M ed. 7 5 : 7D6, 193r, B eh re n s, B ehrend, an d B au m an n , A n n y : Z u r Phannakologifc #es Bleis: IX . M itteilung, Z tschr. f. d. ges. exper. M ed. 2 : 16, 1933. V 12. Bell, W . B .: Some A spects of the C ancer P roblem , New Y ork. W illiam W ood & Co., 1930. 13. G ettler, A . O ., and N orris, C harles: Poisoning from D rinking Radium W ater, J . A. M. A. 1 0 0 :4 0 0 (Feb. 11) 1933, 14. Y oung, A . G .; T aylor, F . H . L ., and M erritt, H . H .: T h e D istri bution and Excretion of M ercury, A rch. D erm at. & Syph. 2 1 :5 3 9 (A pril) 1930. lished observations are reproduced here to indicate the! size of this excretion in cases of lead poisoning wb the patients were hospitalized on a rigid, constant,' m eta^ bolic regimen.144 The first value, determined in chart indicates the rate of lead excretion during the subsir f-. dence of an acute lead colic. This chart shows how'rJ closely that rate of excretion is again approached dur- ing deleading and indicates that the rate of excretion is of a very different order from that ascribed to food and the "normal" lead con tacts of daily life. In con trast to this, chart 2 indi cates that lead may be pulled from the bones two years after every known exposure has ceased. The large ex cretion during this first course of deleading indi cated that the patient had had a considerable previous exposure and storage. In these two observations the effect of medication is obvious when superimposed on a diet already low in calcium. But the increase of lead excretion is not in variable. We have had one patient, maintained through a long period on a low calcium diet, in whom the lead excretion was not fur Trve-ScyWervois ther increased by adding ammonium chloride, even though the calcium excre tion was somewhat accen tuated. But the usual result is that increased excretion of bone calcium is accom panied by stored lead. In our experience, any method that increases cal C h art 2.-- Lead excretion in a young man removed from all in dustrial lead exposure for eight een month*. H e bad a toxic am blyopia but had received no previous tre atm en t for lead poi soning. The first period indicates th e excretion d u rin g low calcium , diet alone, w ith au b seo u en t addi- :ar/j tion of am m onium chloride and parathyroid extract-Collip. The recorded u n its o f parath y ro id ex-, tra c t w ere the old units (five times stronger than in the new 1934 n o m en clatu re). v cium excretion also increases the lead excretion. No deleterious effects have resulted J since we have learned to apply medication in amounts $ gradually increased over a period of a week or ten days.'-* The value of these therapeutic suggestions can best *"* be gleaned from the experience of others, and recent ' reports in the literature in this regard have been pre-'^' dominantly favorable. The clinical value of high calcium therapy to quiet the toxic episodes of lead intoxication 14 has been con firmed by Badham and Taylor,4 Belknap,1* Wiegeldt,11; H . T b e u p p er block, in ,11 c h a rt, rep resen t m edication nxpresaed cubic centim eters of molar solution given daily by mouth. Tbe baae^-A line of the rem ainder of the charts is the middle horizontal line m arked r ~ 0. T h e c h a rt ex tends both ab o v e a n d below th is lin e---the f a r t h e r <? from this middle base line, the higher the value. Above th is midd base line is ahown the lead excretion expressed a s le a d : excreted three-day period*. The lighter line is the u rin ary excretion," the heav ier r line the total excretion in both u rin e and feces. Below the middle base V line tbe charts extend downward an d indicate the calcium m etaboligtn^^^l T be calcium intake is hatched below the base line. W hen fenced I n j 'l t V ^ in d icates a low calcium in ta k e av e ra g in g 100 m g . Tpf calciu m d d t r '. ? T he areas th a t have no enclosing block lines indicate a diet am ple ,fn * calcium . T be calcium excretion represents the total cak iam i n b o t b j S alter W . T .,'.an d `Aufcg? i f calcium CUorido to R d PoruU lU c P ,.n . J . A , M . A . > (A pril 11) 1931. 16. Belknap, E . L .: Lead Poisoning: T h e D iagnosis an d T r e a t e d of Its Most Common Toxic Episode, Lead C olic, W isconsin M . J . 346 (A ug.) 1929. - .*>.. y 17. W iegeldt, cited tnr Teleky, L .t Moderne Thera pie d c rB ld v e rm ftS tung, M uncben. med. W chnschr. 7 8 : 354 (Feb. 27) 19 3 L LEAD IN THE BODY--AUB 89 sj Koyranskiy,7* and by many in personal acts as the body's support. The trabeculae, scattered . _Tr--irn,.^--v"aHons. It is the type of therapy that can through the marrow, particularly at the epiphyses, -act ' ' p - r j l y be judged by its striking clinical effects. Noth- as the readily available supply of calcium for body ' ,v,* dramatic in treatment can be desired than the needs. It is this relatively small lace-like trabecular . - '! - ^ ' nnid subsidence of lead colic following the slow intra- structure, with its large blood supply, which is depleted . injection of 10 cc. of a 20 per cent solution of when calcium is demanded by the body--or refilled calcium gluconate. Reduction of lead excretion by a when calcium is stored.17 The hard cortex, which con- 1 -f- high calcium diet has been confirmed by Litzner, stitutes most of the bone with its relatively small blood v A W'eyrauch and Barth.*0 supply, probably metabolizes at a fairly constant rate. - '-'ri Increase of the excretions of heavy metals by the In the trabeculae, lead is stored in relatively high con- '-.h liberation of calcium stores has also been extensively centration. This w e15 showed by analyses some ' studied, and our results were confirmed in one par years ago, and it has recently been dramatically con- '"H ticular or another by many authors. Litzner, Weyrauch firmed by Behrens and Baumann 10 by means of their - and Barth * confirmed the influence of sodium bicar beautiful pictures of radioactive deposits. It is largely Vi bonate but were unable to confirm the effect of acidosis. the salts in these trabeculae that are liberated in time 'T They determined lead excretion only in the urine, and of calcium need. . it has been our experience that most of the increased However, it is essential to realize that probably not lead excretion appears in the feces. Certainly, urinary all the calcium and lead that is liberated from this bone lead alone is not an adequate test for total lead excre is excreted. There is x-ray evidence to indicate that it tion. The other publications have shown that acid- may circulate and be redeposited in bone, especially in producing substances,11 parathyroid extract,1? and large childhood, for the roentgenograms of Vogt00 show that > doses of viosterol ** increase the rate of excretion of lead, radium ** and mercury.1* In five cases of lead colic studied with Dr. Marion Ropes, we could deter mine no influence on lead excretion from daily injec tions of 1 cc. of sodium thiosulphate. This agrees with the negative results on animals of Curtis and Young.15 Shelling has also shown by growth curves in rats that phosphate may be important in regulating the deposit of lead. This may well be the case also in children, in whom the normal diet tends to be high in calcium but relatively inadequate in phosphorus. In adults, how ever. the average diet is low in calcium and the phos phate intake is more than adequate, so that the calcium intake is the easy one to control. It thus appears that the overwhelming evidence of the past ten years confirms the view that the lead stream and the calcium stream run in the same direction whether these substances are being deposited in the bones or liberated into the blood and into the excreta. To understand this mechanism thoroughly one must turn to the metabolism of bone. It has been demon strated 17 that bone can be considered roughly divisible into two functional elements. The hard cortical bone C hart 3.-- Lead excretion determ ined for three and one-half months in a patient whose acute symptoms of lead poisoning subsided before the observation was started. . .: > ' 18. Leacbke, E .: F o rtsc h rittc in d cr E rk e n n u n g u n d B ehandlung der v/icbtigrten V ergiftungen, M unchen. med. W chnachr. 78 s 1657 (Sept. 25) the lead gets repeatedly dissolved and redeposited along v 19. K oyranrkiy, B. B .: L ead Poisoning-- C alcium C hlorate in ProphyUxiB and T herapy, Sovet. v rach . g ar. 647 (J u n e 15) 1932: a b itr . J . A. M. A. 8 9 s 1304 (O ct. 8) 1932. 20. Litzner, S .; W eyrauch, F ., an d B a rth , E . : U n tersu ch u n g en fiber Hleiaimcbeidung durch bestimmte K ostforroen u nd A rrneim ittel beim Menschen, Arch. f. G ewerbepath. u. Gewerbehyg. 2 : 330 (Ju ly 6) 1931. 21. Tcharny, A ., a n d Iira ilew iU ch , E .: Z u r P athologie des Stoff^chsels bei B leivergiftung des O rg a m sm u s: IV . E in flu sr d er S alssau re oaf die V eranderung des Phosphor und C alcium um satres bei experiBsenleller B leivergiftung, A rc h . f. G ew erbepath. u . G ew erbehyg. 2 : 56 ^ 1931. Rabinowitch, I^8M .; D ingw all, A ndrew , and Mackay, Studies on C erebrospinal F lu id : I I . T h e O ccu rren c e o f L ead in Cerebrospinal Fluid, J . Biol. Chem. 1 0 3 : 725 (D ec.) 1933. 22 H unter, Donald, and A ub, J . C .: Lead S tu d ie s: X V . T he Effect i ^ Parathyroid Hormone on the Excretion of Lead and of Calcium the epiphyseal line of growth. It is because of this great avidity of growing bone for salts, as well as the diffi- V \ culties precipitated by calcium deficiencies, that delead- V- ... ing therapy seems an unwise and unsuccessful proce-: dure in children. . i The present problem of treating lead poisoning lies ' \ not in the methods, for efficient methods exist. The ."> problem that remains to be decided is Should deleading be undertaken or avoided? If rapid deleading is to b e . ( J a n ) *1927 *rom Poisoning, Q u art. J . M ed. 2 0 : 123 avoided, it is necessary simply to give a large calcium Z J F lin n , F. B., .n d Sm ith A dtlxide R .: T he Effect of Vioateroi on Excretion of E e id .T . In d u it. H r(f. 1 5 :1 5 6 (M a r) 1933. T aylor, *od Weld, C. B .: The M obilization and Excretion of Calcium v ? Over-dosage w ith Irra d ia te d E rgosterol, B rit. J . E xper. P ath, a s 109 (A pril) 1932. FIinn, F. B .: E lim ination of R adium Salta from the H um an Body, t A . M. A. : 1763 (M ay 23) 1931. F lin n , F . B ,, and Seidlin, S . M .! ru ra th o m o n e m th e T re a tm e n t of 1`R adium P o is o n in g " : A P relim in a ry " prrt. Bull. Johns H opkina H osp. 4 5 : 269 (N o v .) 1929. 25. Curtia, A . C ,, an d Y oung, A . G .: E ffect of S odium T hiosulphate `" ." '.E ic re tio n of Lead, J . f a b . & Clin. M ed. 1 3 : 628 (A p ril) 1928. r Df ' of. D ietary Calcium an d Phoaphorus on T o p o ty of Lead in the R at: Rationale of Phosphate Therapy. Proc. Son Exper. BioL & M ed. 3 0 : 2 4 8 (N o v .) 1932. 27. Bauer W alter; A ob. J . C-, and A lbright. F u lle r: Studies of yaicium and Phosphorus M etabolism : V . A S tudy of the Bone Tra- a Readily Available Reserve Supply of Calcium , J . Exper. intake in the diet. This lowers the body's demand calcium stores, so that calcium is even stored, and the only excretion of bone calcium (and lead) comes fromV? the normal metabolism of the bones. Obviously, t h i s ' is the method that should be used (Juring any. toxic lead episode. ,. . ------------------------------------------ ;---------------- ---- vf: 28. A ub, J . C .; Robb, G. P ., nd Rossraeisl, E lsie: The Significance of Bone T rabeculae in the T reatm ent of Lead Poiaooing: Lead 'Studies 17, A m . J . P ub. H ealth 2 2 : 825 (A ug.) 1932. - - 29. B ehrens. Behrend, and Baum ann, A nny: Z ur Pbarmakologie' dea B leis: X . M itteilung, Ztachr. f. d, ge*. exper. M ed. 9 2 : 251,-1933. ' ' . . Y '1, . ) 30. V ogt. E . C .: A Roentgen Sign of Plum bum , Am. J . Roentgenol. 2 4 : 550 (N ov.) 1930. >.;& ' ?: -; But should deleading be undertaken after the episode has subsided? To help in this decision, one must remember that: 1. Lead is stored in relatively large quantities in the area of bone readily available for liberation. 2. The liberation of this store is an obvious factor in the onset of toxic lead episodes during metabolic upsets. 3. This liberated lead may not be excreted but may circu late and be redeposited. (No one knows the extent of this possibility.) Therefore, in favor of deleading is the possibility of reducing, under controlled conditions, the lead contami nation in the bone trabeculae and then replenishing the trabeculae with uncontaminated calcium. Against deleading is the consideration that it may be desirable to avoid the liberation of lead, which can be kept largely stored in the bones during good health. From the theoretical point of view, deleading seems advanta geous in order to avoid sudden liberation of this lead in time of metabolic stress. From the practical point of view the answer is dependent on which procedure will advance most promptly to a. recovery of health. In my experience, following the ordinary toxic lead episode, a vigorous course of deleading is usually fol lowed by a prompt recovery to normal health -- a recovery that is more rapid and much more complete than when a continued deposit of lead stores is main tained. In lead palsies, I have the impression that thorough deleading approximately halves the period of disability. This opinion, formed from many observa tions, may possibly be altered, but the biochemical knowledge on which this treatment is based seems to be thoroughly established, not only for lead but also for several other related heavy metals. 695 Huntington Avenue. NORMAL ABSORPTION AND EXCRE TION OF LEAD ROBERT A. KEHOE, M.D. FREDERICK THAMANN, Ch.E. AND JACOB CHOLAK, Ch.E. CINCINNATI A recent series of articles in another journal has detailed the methods and the major results of our studies of lead absorption and lead poisoning during the past ten years.1 So far as they are concerned with normal lead absorption and excretion, the results may be sum marized briefly as follows: 1. Two groups of native Mexican Indians, whose mode of life and environment were devoid of opportunities for contact with the leadcontaining products of highly organized and industrial ized populations,*were found to have lead in their blood and to excrete lead in their feces and urine, as a con sequence of the occurrence of lead in the soil and hence in vegetation and animal products employed as food. From the K ettering Laboratory of Applied Physiology in the U niver sity of Cincinnati. Read before the Section on Preventive and Industrial M edicine and Public H ealth a t the E ighty-Fifth A nnual Session of the A merican M edical A ssociation, C leveland, J u n e 13, 1934. 1. (a ) K ehoe, R . A .; T h a m a n n , F re d e ric k , and Cholak, Ja c o b : O n fche N orm al A bsorption ^nd E x c retio n of L e a d : I . Lead A b sorption and E x c re tio n in P rim itiv e L ife : I I . L ead A bso rp tio n and Lead E x c retio n in M odern A m e ric a n 'L ife ; I I I . T he Sources of N ormal Lead A bsorption; IV . Lead A bsorption and Excretion in In fan ts and C hildren, J. Indust. H y g . 1 5 : 257-305 K S ept.) 1933; (6 ) L ead A bsorption an d E x c retio n in C ertain Lead T rades, ibid. 1 5 : 306-319 (S ep t.) 1933; (c) Lead A bsorp tion and Excretion in Relation to the D iagnosis of Lead Poisoning; ibid. 1 5 s 320-339 (S ept.) 1933. 2. Various groups of healthy children and adults in* United. States, with no occupational exposure, shown to have lead in their tissues and in their ex chiefly because of regular ingestion of lead with th foods. 3. The rate of lead excretion among Ameri is higher than that observed in people living under simpler and more natural conditions (native Mexicans)t in correspondence with the higher lead content of cer tain American foodstuffs. 4. Evidence was obtained that the ingestion of these "normal" amounts of lead does not result in steady accumulation of lead in t! body. Apparently an equilibrium is reached after a* time, so that a substantially constant concentration of lead remains in the tissues, and lead output becomes' equivalent to lead intake. Table 1.--Distribution of Analytic Results Obtained on Nine' Normal Subjects M illigram s of Lead 24 H o u r Sam ples 24 H o u r Sample* of Food o t Ftcea 0-0.09............................................... 0.10-0.19............................................... 0.20-0.29............................................... 0.30-0.39............................................... 0.40-0.49............................................... 0.50-0.50............................................... 0.60-0.69............................................... 0.70-0.79............................................... 0.80-0.89............................................... 0.90-0.99............................................... 1.00-1.40............................................... 1.50-1.99............................................... 2 .0 0 + .................................................... 424 421 171 64 40 17 8 6 S 2 14 1 et 516* 500 303 149 87 35 14 7< 6 > 2 1.0. St T o t a l ................................................... M ean.................................................... P ro b a b le e r r o r o f m e a n ............... S ta n d a rd d e v ia tio n ........................ 1,176 0.1761 0.004 0.180 1,631 0.1931 0.003 0.168 show lead. t E lim inated in calculation o f m ean. C alculated on a wider d istribution o f result*. Table 2.--Means and Their Probable Errors of Observations''[ on Nine Normal Subjects S u b jec ts .T. H ............. S. J .............. C. H. no. 1 .... C. H. no. 2 .... .1. McS. n o . IV. J . McS. no. 2.. J . A. B ............. H . G. R . .......... L. S........... E . C .................. Lead In Urine L e ad In Feces Mg. per L ite r 0.017 0.001 0.025 0.002 0.022 0.001 0.029 0.002 0.026 0.081 0.022 0.001 0.020 0.002 0.015 0.001 0.024 0.001 0.014 0.001 Mg. per 24 H o u rs 0.027 0.021 0.025 0.028 0.032 0.026 0.020 0.014 0.020 0.014 Mg. Gm. per Ash 0.027 * : 0.001 0.040 h ; 0.002 0.090 z : 0.003 0.123 : : 0.006 0.064 : ; 0.004 0.037 : ; 0.003 o.oei r : 0.003 0.069 - : 0.003 0.053 : : 0.002 0.040: : 0.002 Mg. per 24 H o u n 0.15 0 .0 1 0.21 0 .0 1 0.23 0.01 0.31 0.02 0.22 0.01 0.19 0 .0 1 0.19 0 .0 1 0.16 0.01 . 0.18 0.01 0.16 0.01 In the course of the work from which these conduf-j sions were derived, certain healthy young men with;: negative occupational histories were kept under obser-f' vation for months, during which their lead intake within food and drink (exclusive of water) was measured! by analyzing duplicate twenty-four hour food samples' and their daily lead output in feces and urine was; determined. Nine such subjects have now been included in our observations. The results have yielded a con-?: sistent picture of normal lead ingestion and normal lead! excretion, as measured by the analytic methods thafL we have described.1* The results are grouped in tablesjf 1 and 2 in such a manner as to bring out the,facts thaf? we wish to introduce as points of departure for the further observations to be described. } ';