Document N2E50k6geeN6wKD4oeKV5BMRw

N Lead Absorption, Lead Excretion and Lead Poisoning by Robert A. Kehoe, Jacob Cbolak, Donald M. Hubbard and Robert R, McHary Prom the Kettering Laboratory of Applied Physiology, University of Cincinnati, Cincinnati, Ohio. The present problems in the differential /" / diagnosis of lead poisoning, in so far as they differ from those of any previous period, arise largely in the evaluation of the significance of the lead exposure of a patient, and the interpretation of the meaning of such lead determinations as naj have been carried out 0:1 the faces, urine, blood, spinal fluid, teeth, skin,or other tissues, in search cf specific evidence of lead absorption. These problems, expressed some what differently, and considered from slightly different view points, are among the m.03t important practical questions in relation to plumbism, both in general medical practice and in industrial hygiene. To the" medical practitioner, the facts In the matter of lead exposure are often obscure. In the case of an r,3 factor in J. line ns until a chance x-ray plate shews suggestive or conclusive evidence cf abnormal lead deposits in the skeleton. In the adult, industrial lead exposure may or may not be suggested by the occupational history. The absence or the occurrence of such suggestion may be equally misleading, since, on the one hand, lead exposure may exist in unsuspected occupations, while on the other, recognized lead trades may be so well regulated as to give rise to little or no exposure. Indeed technical and operating changes are carried out in modern plants with such disconcerting speed and frequency, that plant physicians themselves are not always conscious cf their hygienic import. Obviously, the doctor who has nb direct and detailed knowledge of plant activities and conditions, cannot be expected to place a. proper value on the history of occupational lead exposure. In many instances, therefore, judgment requires that he base his opinion as to the severity of the exposure on specific evidences of lead absorption, rather than on non-specific clinical evidences of injury. In the case cf the industrial physician, the significance cf the lead exposure in a plant can become partially known, in: tim.e, through its clinical effects upon the plant population, but it cannot be anticipated or properly appreciated without recourse to cone precis means for measuring either the magnitude of the potential exposure, or, preferably, the physiological response to exposure in terms cf the lead absorption and lead excretion of the workmen. Sven with the necessary facts available as to the nature: and magnitude cf the lead exposure, an interpretation of their clinical significance may still be difficult, particularly if the exposure is known to be slight. r r* 00 The reputation cf lead a3 an insidious poison the minutest quantities of which, if absorbed l tedl-7 over a prolonged period, might accumulate in the body v;ith disastrous results, has long been established both in the medical and the lay mind. Gradually physicians with experience in the lead trades, who noted the results of various types and degrees cf lead exposure, came to believe that lead absorption did not cause injurious effects if it did not exceed certain limits. The original distinction between dangerous and essentially harmless occupational lead exposure was based on observations of workers rand plants, without benefit of quantitative methods of study, h'lth the recognition of the greater significance of inhaled lean as compared with ingested lead and with the de velopment of satisfactory methods for the estimation of particulate lead in the air breathed by workmen,, the existence of a threshold x value for toxic lead absorption has apparently been established. However, many physicians, physiologists and pharmacologists have either disregarded the observations made in this field or haveconsidered them with suspicion and skepticism. Only recently has evidence been obtained from the study cf human lead absorption and excretion under a variety of conditions, which substantiates the position taken by the industrial hygienist. Because the meaning of this evidence has not been fully appreciated, it seems well tc outline it here, not only in relation to lead absorption on the part of the general population and to the diagnosis cf lead poisoning In the hands of the average clinician, but also as a basis, in principle, for industrial practice. The presence of lead in the tissues and in the excreta of normal individuals, quite apart from any occupational exposure to lead compounds, is now established. In 1933* v,e reported In detail the data of cur studies up to that time and reviewed the observations of other workers (1, 2, 3). Since the publication of these reports, many additional contributions have demonstrated the occurrence of lead in the skeleton (in cluding; the teeth) (If., 8, It 9> 10, 11), the soft tissues \1, 11, 12, 13, 1 Ip, 15) (including the brain (9) and the cerebro-spinal fluid (16, 17), the blood (18, 19, 20, 219ZZ(`**') urine (9'l8, 20, 22^' 23, 2I4., 25, 2c, 27, 28) and feces (20, 2c) of normal; persons of all age3 and occupations. An examination of the results obtained by different analysts in various parts of the world shows them to be In remarkably close agreement, with due allowance for variations in the sensitivity and accuracy of the analytical methods employed. The general pattern of normal lead metabolism which we have described in relation to the American population seems to have been confirmed, not only in the .uerican environment but In the several countries in which, similar observations have been made. Of particular interest to us ir this connection are the results obtained by Lynch and his associates (p) on the lead content of the'bones of oresunably normal p e r 3 on s_ |J, d read Britain), and those of Tom.pcecfc and Anderson (9), and Tcmpsetfc (10) _n the `lead content, cf the skeleton and soft tissues cf human fetuses and human beings of widely varied ages (Great Britain). These data would seem to show that the lead content of the tissues of a normal child and of a normal adult as reported by us (2),. was of an order of magnitude fairly characteristic of normal human beings in general. V/e are justified,; therefore, in making a confident restatement of the facts with regard to normal human lead metabolism in their simolest terms. The adult American ingests lead in his food and drink to the extent of approximately 0.25 milligrams per average day (20) (He probably inhales a small quantity of lead from the air he breathes'(29, 30, 31, 32, 33> 3k> 35) > although the amount inhaled and the proportion absorbed from that which is inhaled are con jectural.) Most of the ingested lead traverses the alimentary tract unabsorbed, but some quantity is absorbed as i3 shown by the constant presence of lead in the tissues, the blood, and tie urine. The mean daily fecal output of lead i3 approximately O.25 milli grams ;2C), while the daily urinary output varies from 0.02 milli grams to 0.10 milligrams (20, 2o), the variation being chiefly related to weather conditions with their attendant influence upon urinary volume (26). The lead of the tissues is distributed in accordance with a definite pattern, with.the major portion in the skeleton (and apparently with a higher concentration in such long bcr.es as the femur (5, 1C), but with measurable and apparently fairly constant quantities In the 30ft tissues, especially in such lo vi.; .Ivor, kidney, spleen and brain (2, 9)* The average gross quantity present in the adult body Is somewhat in doubt, because cf the paucity of data,out it is probably not less than 12j mg, nor more than*200 mg. with due regard to variations in body weight (2, 5,9,10,5) Barth (56) -supplied data which in his opinion pointed to a progressive elevation of the lead concentration of the skeleton with progressing age. However the differences between youth and old age were too slight and too irregular to be con vincing. Tompsett (10) found similar and even larger variations in different bones of the same skeleton and in the skeletons of different : pers on3 within the same age group. Tire combined facts furnished by the study of the tissues and excreta Indicate that within certain limits, of ^.r^t^e, a state of dynamic equilibrium is maintained in which progressive lead accumulation ir. the tissues does not occur, intake and output having cone into balance after a certain level of absorption has been reached. Significant variations in absorption and excreti.n occur from day to day, but the normal.metabolism of lead, as compared with that of the more common metallic constituents of living material, is remarkably stabile. bhether or1 not lea.i is useful in physiological mechanisms is an open question at present, but regardless of the eventual, answer to this question, the concept of lead as an accumulative poison, without regard to quantity, has received its death blew. Zlsevihere, we have interpreted the foregoing facts in their relation to the diagnosis of lead poisoning (37> 38). It is not cur purpose here, therefore, to give further detailed con sideration to this aspect of the subject, be merely wish to stress, the necessity for taking strict account of the .limits of normal (> variation in the clinical interpretation of data on the lead content of the tissues or the excrete of oatients. In view of :now ledge of the normal picture and cf deviation i r.du ced abnormal re to lead compounds. lead analyses of various e their p lace as invaluable dl:.. .gnostic aids, an- .1 ' s ureful clinical and medicc-logal evidence, llowevor, rush procedures become useless and even grossly misleading unless they are carried out with precision and interpreted with duo regard for the available knowledge as to the behavior of lead. Hore-over, analytical data cannot be substituted for sound clinical observations in any of the fields in which they have come to be useful adjuncts. The ultimate sources of the lead wnich is found in human food:merits further consideration and further detailed study. As we have pointed out previously (39) the increment cf lead content above that which is a normal constituent of cur food substances, is due to contamination from a great variety of sources, some of -which are cf recent and some of earl'er origin. A number of the earlier sources of contamination of food and drink have disappeared, some by accident and others by intent. Our data on the fecal lead output of normal persons in various parts cf the United States and Canada, as collected over a period of more than a decade, do not give evidence of a tendency toward a pro gressive increase in dietary lead. This is not to imply that our sampling of the population has been such as to yield adequate information on the e::tent or the causes of variation in these respects, lievertheless via have been struck by the essential uniformity of the data obtained from year to year, and vje doubt the occurrence of any recent progressive incrc?ase in the lead intake of : the American population. V/e do not suggest, however, any cver-cc/nfidekt relaxation of the efforts being male by these / engaged in the supervision, handling, and processing cf cur food materials, to prevent' contamination with lead. An ultimata basis for determining the_limits of safety in the matter of lead so: "1 p V- V, ^ j - -1 me and the indu3 trial-ppulati on, can be found only In fart'.or experimental studies of the fate of leal whan introduced into the human body- through various avenues cf entrance, he have illustrated certain .abnormalities in the load content cues md excreta of persons exposed to abnormal quantities of lead both of occupational and non-occupational origin (I4.0). In observations made chiefly in various lead trades, we found a correlation between the rate of lead excretion and the severity of lead exposure. The available data appeared to indicate that within certain limits of increasing si 01 51:0 exposure and presumable abocrption, there was a proportional increase in the urinary excretion; with further increases in exposw there was a progressively diminishing increment of increase in the excretory response. There was also an incompletely defined relationship betvieen the magnitude of the lead exposure, as por trayed by rate of lead excretion, and the occurrence of lead in toxication among the workmen. V,re came to the conclusion, which Shiels (41) has since reached from his observations, that lead poisoning may be expected to occur under occupational conditions in which lead is excreted by representative workmen at a mean rate above 0,21 mg. por liter in the urine. In subsequent plant studies we have kept in mind the need for defining more precisely in terms of lead excretion, the highest level of lend exposure compatible with complete freedom from clinical- load intoxication. Is evidence of some progress toward this goal, the following ?'3cont observes! ons are reported. # Groups of men, selected as representative of the various occupations in three different industries, were examined -h -a - \hods -which we have detailed previously {[4:' * r/r a. n j u s samples of blood, urine .and feces, as indicated in the data, wore obtained with "OTT tat-1 e crecaut; 0r.a a - ai r. 0/ o vd j .^a1i . ion. work of each group involved exposure only to particulate inorganic lead compounds. The men tn Croup A. all engaged in the same genera type of viork, handled a finished .material which contained lead ' n a essenttally insoluble form In a siliceous base. 'The conditions of The full data of these studies will be piven elsewhere. Brevity necessitates use of only those items of information and data which illustrate the points under discussion here. i *r< O y> not thought to be such as to permit absorption of lead to more than a theoretical extent. The men in C-roup 3 were employed in various types of soldering activities, but all had the same type, and apparently about the same degree of exposure to homos of molten lead an-'1 to finely divided metallic lead and lea: oxife. The men in Oroup C mere likewise exposed only to fume 3 and to particulate lead resulting from varied types of operations with molten lead and lead castings. However the operations in this plant, as represented by this small group of workmen, involved 3omevihat variable degrees of lead exposure of a generally greater severity than that of the other plants. Ike clinical data on groups A and 3 were entirely devoid of evidences of lead absorption or lead intoxi cation. In the case of f-rcuc C, however, certain individuals were seen to hav i absorbed lead in sufficient quantity to pro luce slight but definite gingival blue lines, Characteristic changes in the blood picture, and slight but unmistakable evidences of neuro-muscular damage. In addition to these objective findings there were scattered but suggestive evidences ;oxic -i. X cos in. the form of vogue gastro-intestinal co,"oloints'. One typical histojfaf a recent episode cf saturnine colic was cb v-.-inec Ho history of fatal or permanently disabling plumbIsm could be elicited from management, plant physician, or employees over the period of their direct knowledge and experience. Improvements in ventilation had been made some two years previously, since which time cases:or suspected cases of incipient intoxication had been cared for either by temporary cessation of employment or more frequently by transfer to work involving loss exposure. 015 6 2 'The age distribution of the vr.en selected to represent the various occupations in each industry, as given in Table 1, Is of interest only because it demonstrates the repre sentation of widely divergent age groups. The duration of con tinuous exposure, shown in Table 2, is correspondingly representativ of both short and long periods, except In the case of Group A in whl the longest period of employment coincided with the life span of the industry up to the time of our observations. The data in Tables 3 and 4 on the fecal output of lead, (results were not available for urouo should be intercrefced in ;n to our vi ous cemon- 3tration of the role of alimentary lead as an approximate measure of the magnitude of exposure In dusty lead trades. The difference between the results on coined in the two groups is not significant^ statistically, on the basis'of comparison of the mean values for lead found In a single fecal evacuation. However, the two groups are significantly different with respect tc alimentary output ( when compared as to their mean lead output per gram of fecal ash. This indicates that the exposure of Group G to particulate lead in the atmosphere was .grew or than that - vi me an values are above mean normal levels. The resul fcsm'on the urii V '3- vt a_ / are muon more significant than those on the ces, both In their gener physiological meaning and In mis cl; Xi ii--w/- ... sJ.G4-*I^1 hi eh they port differences in the ie-.G absorption of the three groups of workmen. The mean rate of urinary excretion for Group A is within normal limits, aswa3 expected; that for Group B is higher, and that for Group C is still higher, both differences being of statistically significant proportions. Thus the analytical results on the excreta correspond to the observed conditions in the plant, and 1 01563 verify the existence of three different levels and absorption, ie; excosure It is a matter of both scientific and practical importance that the results obtained on samples of blcoi (Table 6) from workmen in Groups A and 3 do not differentiate these two groups with respect to their absorption of lead. It is probable that a differentiation would have been effected if a larger number of blood samples from Group 3 had been analyzed, furthermore three analyses on blood from individuals in Group C, yielding 0.09 nig., 0,2p mg., and 0*14-9 mg'* per 100 grams of blood, leave little doubt as to the status of the group in. tills respect, nevertheless, the fact remains that with due regard to the numbers of samples available ;for analysis, the results on the blood do not yield a3 definite evidence as those on the urine, with respect to the conditions under study, (The mean value of 0.078 i 0,007 for the urinary results which correspond to the fourteen analyses on the blood in Group 3 Is significantly greater than the mean for Croup A.) The reason for this can be found, we bolleve, in physio 1 ogi-ea 1 considerations Tirinary lead excretion varies from person to person and in the cane persons with a variety of individu: determinations of the particulate 1 ead In the atmosphere c-- v-i + j. ant 3, as carried out with s tandarc metho Is by other observers a somewhat earlier date, provide useful correlative data. Hie observe lead concentrations ranged from 0.033 mg. ?b up to O.63 mg. ?b per cubic meter of air, with a mean value of 0,21 + 0.02 mg. ?b per cub i / meter in thirty-one air samples taken from various parts of the plan 01 r y- A b0g and environmental factors . Honever, the concentration of lead in a sample of urine collected over a period of twenty-four to seventy-two hours, in accordance with cur practice, shows some degree of response to all the physiological factors active during that period, including variations in lead absorption. k single blood sample, on the contrary, illustrates only a momentary physiological state, which, under essentially constant conditions of lead exposure, may conceivably represent the general level of the lead metabolism more adequately than a sample of urine, but which under cona tions of variable o: intermittent excosure could scarcely be expected to do so. Tho clinical and analytical data as a whole do not justify sweeping conclusions, further study of these rent basic levels lead in terms of lead metabolism. ) .ich is compatible with human represent another step toward shat goal. 01 56 13 1* Kehoe, R. A., Thamann, F, and Cholak, J.: On the normal absorption and excretion of lead, I. Lead absorption and excretion In primitive life, J. Indust. Hyg., 15. 257* (1933). 2. ...................... On the normal absorption and excretion of lead, II. Lead absorption and lead excretion In modern American life. Ibid, 3&, 275, (1933). 3. ...................... On the normal absorption and excretion of lead, IV. Lead absorption and excretion in infants and children. Ibid, 1* 301, (1933). if. Kehoe, R. A.: Unpublished data. 5. Lynch, G. Roche, Slater, R. H. and Osier, T. G.: Determination of traces of lead in biological materials, with special referen to bone. The Analyst, 59. 787* (193^). 6. Maulbetsch, A. and Rutlshauser, E.: La teneur des dents en plomb. Arch, internet, de phanaacodyn, et de therap., 53, 55* (1936). 7. Pernice, H.i Die Leber bei Biel- und Komblnatlonsvergiftungen. Arch, f, Gewerbepath. u. Gewerbehyg., Jx. 538, (1936). 8. Pfrieme, F.: Ueber den normalen und pathologischen Bleigehalt der Z&hne von Menschen und Tieren, Arch. f. Hyg., 111. 252, (19: 9* Tompsett, 13. L. and Anderson, A. B. The lead content of human tissues and excreta, Blochem. J., 22, 1851, (1935) 10. Tompsett, S.L.: The distribution of lead in human bones. Ibid, 30, 345. <19?6). 11. Weyraueh, P. and Mfiller, H.: Das sog.nannte normals Biel im manschllchen. S&rper, Ztacbr. f. Hyg. u. Inf ektionskr., 115. 216, (1933) 12. Boyd, T. C'. and De, H. K.: Some applications of the spectroscope in medical research, Indian J. Med. Research, 20. 789* (1933) 13. Esser, A.: Klinisch-anatomische und spektrographlsche Untersuchungen des Zentralnervensysterns bei akuten Metallvergiftungen miter besonderer Berficksichtigung ihrer Bedeutung fur gerichfclic Mediain und Gewerbepathologle, II., Dtsch. Z. gerlchtl. Med., 26* k30, (1936) lij.. Okajlma, S.j Spectral analysis of metals, especially heavy metals, in every part of the organs of the Japanese, Acta Schol. Med. Univ. Imp. Kioto, 1, 1+17* U93D 15. Sheldon, J.H. and Ramage, H.i A spectrographic analysis of human tissues, Blochem. J., 2^, I6O8, (1931) v -ZtiiTp**; iP 01 r C f 0 C b - ll+ - 16. Rabinowitch, I.M., Dingwall, A. and Mackay, F.H. : Studies on cerebrospinal fluid, II. The occurrence of lead in cerebrospinal fluid, J. Biol. Chem., 105, 725, (1955) 17. Schmitt, F. and Basse, V'.: Bleluntersuchungen im Liquor cerebrospinalis Normaler und Bleikranker, Klin. Wschr., l6, 65, .(1937) -- 18. Bass, E.: Die Beziehungen des klinischen Bildes der Bleivergiftungen zum Bleigehalt in Blut und Urin, Deutsche med. Wschr., 59, 1665, (1933) 19. Dutoit, P. and Zbinden, C,: Analyse spectrographique des cendres de sang et d'organes, Compt. rend. Acad. d. sc., 188, 1628, (1929) 20. .21 zv?> -2. ? Kehoe, R.A., fhamann, P. and Cholak, J.: Normal absorption and excretion of lead, Jr. Am. Med. Assoc., lOii, 90, (1935) Telsinger, J.j Eine rasche mikropolarographlsche Methode zur auantitativen 3estimmung des Bleies im Blut, Ztschr. f. d. ges ex per. Med., ^8, 5 20, (193^ K.j ^ }<u Vw.' yw -v, -; ^4". . J** f"'"'**** */ XoJ J, ' Berg, R.: Das Vorkommen atltener Blemente i*n ''''den Nahrungsmitte] und menschlichen Ausscheidungen, Biochem. Ztschr., 165, 1+61, (1925) 23* Boyd, T.O.: Lead in the urine, Indian J, Med. Research, 20, 75j (1932) ' 2I4.. 2rd83, I.: Lead poisoning and its determination f^rom k chemica] point of view, Samm. v. Vergiftungsf., 11, (193^)/ 25. Horton, B.T., Powelson, M.H. and Osterberg, a .E.: Incidence of lead in urine in patients with oeripheral vascular disease, Proc. Staff Meet,, Mayo Clin., 296, (1929) ; Kehoe, R, A., Thamaan. F. and Cholak. J.lj 2o. /An appraisal of the lead hazards associated with the distribution and use of gasoline containing tetraethyl lead, II The occupational lead exposure of filling station attendants and garagftjsechanics, J. Indust. Hygc and Toxicol., l8, I4.2, (1936) 27. Ross, J.R. snd Lucas, C.C.: A new method for the determination of minute amounts of lead in urine, J. Biol. Chem., Ill, 285, (1935) ------ 28. Behrens, B. and Taeger, H.: Quantitative Bestimmung der Bleiausscheidung im Harn Gesunder und Bleikranker mifc Diphenylthiocarbazon, Ztschr. f. d. ges. exper. Med., 9> 282, (1935) 29. Bloomfield, J.J. and Isbell, H.S.j'The presence of lead dust and fumes in the air of streets, automobile repair shops, and industrial establishments of large cities, J. Indust. Hyg., 1, ll&, U933) 30. Dunn, J.T. and Bloxam, H.C.L.: The occurrence of lead, copper, zinc and arsenic compounds in atmospheric dusts, and the sources of these impurities, J.Soc. Chem. Ind., 52, l8S (1953) 01567 - 15 - 31. Pinal Report of Departmental Committee on Ethyl Petrol, Minis try of Health, London, 1930, 32. Fuchs, W.: Rare elements in German brown-coal ashes, Ind. Eng. Chem., 2J, 1099, (1935>* 35. Goldschmidt, V. M.: Rare elements in coal ashe3, Ind. Eng. Chem., 22, 1100, (1935)* 3I4-- Hartley, W. N. and Ramage, H.: The mineral constituents of dust and soot from various sources, Proc. Roy, Soc., London 68, 97, (1901) 35 Public Health Bulletin No. 163* The use of tetraethyl lead gasoline in Its relation to public health. Treasury Department, U. S. Public Health Service, Washington, D. C., 1926. 36. Barth, E.: Untersuchungen fiber den Bleigehalt der menschlichen Knochen, Virchows Arch* f. path. Anat., 281, llj.6, (1931) 37. Kehoe, R.A., Thamann, P. and Cholak, J.s Lead absorption and excretion in relation to the diagnosis of lead poisoning, J. Indust. Hyg., 3, 320, (1933). 58. Kehoe, R. A.: The diagnosis of lead poisoning in the light of recent information, J. Med. (Cincinnati), 16, 527# (1935)* 59. Kehoe, R. A., Thamann^ F. "and Cholak, J.: On the normal absorption and excretion of lead. III. The sources of normal lead absorption, J. Indust* Hyg., 1*5. 290, (1933). l+C. ............... ........Lead absorption and excretion in certain lead trades. Ibid, 1, 306, (1933). l+l. Shiels, D. 0* s The concentration of lead, in the urine of workers at Mount Isa Mines Limited, Queensland, with special reference to its value In the diagnosis of lead poisoning, Med. 3 Austrai-fee, 1, 559, (1936). 42. Kehoe, R. A., Thamann, P. and Cholak, J.: An appraisal of the lead hazards associated with the distribution and use of gasoline containing tetraethyl lead. Part 1, J. Indust. Hyg., 16, 100, (193U. Distribution of Persons Dmployed in Three Lead Industries Accord in,5 to Age Age In Years 20 - 2It 25 - 29 5 o - 3k 33 - 39 4o - 44 h5 - k-9 , ;o - 5!+ 35 - 59 6o or more / Total m i-ndustry A 2 /'1 5 4 a<L 2 3 27 . Frequency m Industry 3 3 2 3 6 3 4 In Industry 0 4 &o. 3 10 2 "T 3 7 36 _ 22 u 69 Table 2 Distribution of Persons Deployed in Three Lead Indus tries Ac to Duration of Continuous ! npoaure in 3 am ?1 an t dins Period. of Exposure .a Years Under i .0 1.0 2.9 3.0 - 4*9 3*o - o.9 / * o - 3.9 9.0 - **. 12.9 13 1 "! r r 1^.9 nor? Total In Indus try A frequency In Indu3 try 3 "iTH Industry C 8 15 6 1+ O 9 43 45 71 3 nX /" ) ^ /5 51 27 30 22 xj P- r*? 0 Distribution of Person: _2>- ri in Tv.'o Lear! niustr-ic to Lead n Single fecal Zvacu ion coomnn Mean Standard Deviation 0.457 z. D*05> ( + 0.30k J, O 05j 'P&r i 0 1 r w ri ^ /i 4 distribution of Persons Employed in Two Lead Indus ie: ccording to Lead per 0ran of Ash In Feces Lead in llilligrams per J-ran of Ash. 0 - o.ok9 0.05 - 0.099 0.10 - G.li# 0.15 - 0.199 'J c- sj 0* ul I4.9 0.25 and over In Industry u 3 lir f-- ( 2 1 4 3 L 0 0 al " 33 Frequency In industry 0 1 / t Q 7 7 Or 35 ` lean standard deviation 0.125 ,+ 0.010 _r O.OSp D.lo4 A( 01 Distribution of Persons Znplo.yed in ' p V Q Q to Concentration i- 1 (i xnoi "J r i n e Accor : in.- -r*3 iiT'- 3 tuauar a Deviation p3 Pv 7J, *7( 0 \-*4^ 3 vj o # 01 573