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 Af TABLE OF CONTENTS PREFACE PAGE (1) THE NATURE OF THE LEAD HAZARDS..................... ................. ............... ........................ .. 5 Hazards Associated with Manufacture of Tetraethyl Lead and Ethyl Gasoline............................................. Possible Hazards Associated with the Use and Distribution of Ethyl Gasoline............................................................. The Distribution and Sale of Ethyl Gasoline............ ................. .. 5 7 11 (2) PREVIOUS INVESTIGATIONS OF ETHYL GASOLINE IN RELATION TO PUBLIC HEALTH .......................................................................................................................... 16 (5) INVESTIGATIONS CARRIED OUT IN 1929-50 .................................................................... 16 The Selection of Experimental Subjects....................................................... Methods of Study............................ ........................ ............................ ....................... Experimental Findings.............. ................................. ............................................. Comparison of the Findings of 1929-50 with Results Obtained Earlier............................................................................... Summary of Certain Findings in Present and Previous Investigations ........................................................ " The Influence of Previous Occupational Lead Exposure ....................... Lead Excretion in Relation to Length of Exposure to Ethyl Gasoline ............................................................................................ 17 22 29 47 48 48 49 (4) INVESTIGATIONS CONTINUED SINCE 1950 ........................................................................ 59 Lead Exposure in the Handling of Ethyl Gasoline................................... 67 (5) SUMMARY........................................................................................................................................ 75 (6) CONCLUSIONS ............................................................................................................................... 77 APPENDIX (I).............................................................................................................................. The Present Status of the Hazards of the Manufacture of Tetraethyl Lead and Ethyl Fluid..................................... 80 APPENDIX (II)...................................................................................................... .................... The Present Status of the Hazards in the Manufacture of Ethyl Gasoline by Mixing Ethyl Fluid with Gasoline .......... 98 APPENDIX (III)......................................................................-............................. The Sale and Distribution of Ethyl Gasoline in the United States to 1952 ......................... .......................................... . 100 / as r* n ooi i o 3  fi fe I Number --I -- ,.i-- TITLES OF TABLES (1) Period of Distribution of Ethyl Gasoline in Various American Cities up to October, 1929. (2) Gross and Comparative Consumption of Ethyl Gasoline in Various Areas of the United States from 1926 to 1929. (5) Average Tetraethyl Lead Content of Ethyl Gasoline in Various Areas of the United States from 1926 to 1929. (4) Distribution of Subjects According to Occupation and Locality. (5) Distribution of Subjects According to Period of Exposure to Ethyl Gasoline. I (A) History Sheet. ! f. (B) i I (C) | (D) Physical Examination Sheet. Neurological Examination. Laboratory Sheet. (6) Distribution of Subjects According to History of Previous Exposure to Lead Other than Ethyl Gasoline. (7) Distribution of Subjects According to Age. (8) Distribution of Subjects According to Certain Subjective Abnormalities, (9) Distribution of Subjects According to Certain Objective Abnormalities, (10) Distribution of Subjects According to Systolic Blood Pressure, (11) Distribution of Subjects According to Haemoglobin in Blood, (12) Distribution of Subjects According to Stippling of Erythrocytes, (IS) Distribution of Subjects According to Strength of Grip of Left Hand, (14) Distribution of Subjects According to Strength of Grip of Right Hand, (15) Distribution of Subjects According to Lead in Faeces. (16) Distribution of Subjects According to Lead in Milligrams per Gram Ash of Faeces, (17) Distribution of Subjects According to Milligrams of Lead per Liter of Urine, (18) Distribution According to Age of G: 'oups of Subjects Not Exposed to Ethyl Gasoline, Examined in 1927. UX 0 01T 3 Titles of Tables - #2 Distribution According to Certain Subjective Abnormalities of Groups of Subjects Not Exposed to Ethyl Gasoline, Examined in 1927 Distribution According to Certain Objective Abnormalities of Groups of Subjects Not Exposed to Ethyl Gasoline, Examined in 1927., Distribution According to Systolic Blood Pressure of Groups of Subjects Not Exposed to Ethyl Gasoline, Examined in 1927. Distribution According to Haemoglobin of Blood of Group of Subjects Not Exposed to Ethyl Gasoline, Examined in 1927. Distribution According to Stippling of Erythrocytes of Groups of Subjects Not Exposed to Ethyl Gasoline, Examined in 1927. l ^24) ; Distribution According to Lead Found in Faeces of Groups of Subjects Not Exposed to Ethyl Gasoline, Examined in 1927. Distribution According to Milligrams per Gram Ash of Faeces of Groups of Subjects Not Exposed to Ethyl Gasoline, Examined in 1927. (26) Distribution According to Milligrams of Lead per Liter of Urine of Groups of Subjects Not Exposed to Ethyl Gasoline, Examined in 1927. (27) Summary of Mean Values of Age, Systolic Blood Pressure, Haemoglobin, and Excretion of Lead in Faeces and Urine, for Various Groups of Subjects. (28) Mean Values of Lead in Faeces and Urine of Filling Station Attendants and Tank Wagon Handlers, Exposed to Ethyl Gasoline, Excluding All Results Obtained on Persons With Other Industrial Exposure to Lead Compounds. (29) Showing Lack of Correlation Between Duration of Employment of Garage Mechanics and Lead Excretion, and Duration of Exposure to Ethyl Gasoline and Lead Excretion. (30) Distribution of Identical Subjects for the years 1927 and 1929 According to Milligrams of Lead Found in Faeces. (51) Distribution of Identical Subjects for the Years 1927 and 1929 According to Milligrams of Lead per Gram Ash in the Faeces. (32) Distribution of Identical Subjects for the years 1927 and 1929 According to Milligrams of Lead per Liter of Urine. (33) Summary of Mean Values of Lead Found in Samples of Faeces, of Lead in Milli grams per Gram of Ash in Faeces, and of Lead in Milligrams per Liter of Urine, for Identical Subjects Examined in 1927 and 1929. KE' 0017325 Preface The experimental work which is the subject of this report was carried out by the staff of the Kettering laboratory of Applied physiology in the uni versity of Cincinnati, Cincinnati, Ohio. The expense of the work was borne by the Ethyl Gasoline Corporation in accordance with an agreement between the Board of Directors of the university and the officials of the Ethyl Gasoline Corpora tion. The report details the hypothetical opportunities for occupational and general lead exposure which are associated with the distribution and use of gasoline containing tetraethyl lead, and describes investigations which have been completed since the appearance of other repo.rts from the same sources. The methods employed in the estimation of lead in human excreta are omitted, since they have been described in detail in a report dated April 1928. The statisti cal study of the data was made by T. J. LeBlanc, Associate Professor of Pre ventive Medicine in the University of Cincinnati. Attention is directed to Appendices 1 and 2, in which some special consideration has been given to the hygienic problems which occur in the manu facture of tetraethyl lead and in the preparation of Ethyl Gasoline. Appendix 3 presents further information in relation to the distribution of Ethyl Gaso line in the United States up to the end of 1931. K E 00173E6 An Appraisal of the Lead Hazards Associated with the Distribution and Use of Gasoline Containing Tetraethyl Lead. by Robert A. Kehoe, M. D.*. 5 1. The nature of the Lead Hazards The development of a motor fuel containing tetraethyl lead raised cer tain questions in industrial and public health which have claimed an unusual amount of attention. In an early stage of the new commercial enterprise it be came apparent that the manufacture of tetraethyl lead and the blending of the concentrated fluid employed in the preparation of the commodity known as Ethyl Gasoline, was an hazardous occupation which furnished unique opportunities for the rapid development of lead intoxication. The serious dangers of these manu facturing processes have no relation to the problem with which we are concerned in the present discussion. However, the initial confusion of the actual hazards of manufacture with the problematical dangers arising from the U3e of the finished fuel, has apparently persisted in many minds. Therefore the distinc tion between them must be made clear. Hazards Associated with Manufacture of Tetraethyl Lead and Ethyl Gasoline. Pure tetraethyl lead is a heavy, colorless, oily liquid which is peculiarly difficult to retain within jointed receptacles and pipe lines. It is insoluble in hot or cold water, but readily soluble in alcohol and acetone and miscible in all proportions with fats and oil3. As might be suspected from the latter property it penetrates the unbroken skin of animals. Indeed skin absorption alone may result in the rapid production of acute illness and death Associate Professor of Physiology and Director of the Kettering Laboratory of Applied Physiology in the University of Cincinnati, Cincinnati, Ohio. KE 00173^7 in experimental animals.1 From a purely physical point of view, the volatility of tetraethyl lead is low, but considered in toxicological terms it is dangerous ly high, since at ordinary temperatures air saturated with its vapor contains ap proximately five milligrams of lead (as PbJ per liter. This concentration is lethal for experimental animals (rabbits) in a few hours,1 a fact which demon strates the ease with which tetraethyl lead penetrates the pulmonary epithelium. Under certain conditions, notably in the presence of sunlight, tetraethyl lead is unstable, breaking down to yield water-soluble, crystalline triethyl lead compounds. Slight agitation serves to suspend these fine crystals in the air, when in a dry state, thereby producing a dust hazard which has the quality unique among lead hazards - of providing sharp warning of its presence, in that a very low concentration of these substances induces irritation of the mucous membranes with weeping and sneezing. The dangers associated with the preparation and handling of tetraethyl lead are fairly obvious, when these properties are recognized, Unfortunately, thiB information was not available when the manufacture of the product was first contemplated. It is not Btrange therefore that when the production of tetra ethyl lead emerged from a laboratory scale into an incipient commercial stage requiring factory facilities, cases of lead poisoning of the most serious type occurred, characterized by the sudden onset of cerebral symptoms and resulting in a high mortality. Without entering into an irrelevant description of the various steps by which Ethyl Gasoline is prepared for the market, suffice it to say that the hazards of the manufacturing processes are inseparably associated with the characteristics of tetraethyl lead described above. The hygienio problem at every point consists in the prevention of skin contact with tetraethyl lead on the part of the workmen, and in the maintenance of conditions under which the 0017328 7 vapor of tetraethyl lead is not present in the air breathed by workmen. Because of the sharp localization of the dangers, they are amenable to exact and adequate control; nevertheless the potential hazards are great, so that safety is maintain ed only by continual vigilance in the prevention of accidents and in the avoid ance of careless practices.* Possible Hazards Associated with the Distribution and Use of Ethyl Gazollne. The hazards associated with the handling and use of the finished pro duct, Ethyl Gasoline, differ both in quality and quantity from those which lurk in its preparation, nothing could demonstrate the difference in the magnitude of the potential lead exposure of the two sets of conditions in a more pragmatic manner, than the failure on the part of Ethyl Gasoline to produce a substantiated case of lead intoxication up to the present {November 1932) after nine and a half years of its continuous use in certain parts of the United States and about eight years for practically the entire United States. This basis of differentia tion is the more significant when one considers that the hypothetical opportuni ties for the absorption of lead, as a result of the distribution of Ethyl Gaso line, are so varied and so widespread as to defy regulation. But there are 1 other points of difference which have not required the test of experience for ' y: their recognition. Ethyl Gasoline contains tetraethyl lead in amounts so small that the solution has lost the essential toxicological properties of tetraethyl ft. lead. Thus, whereas tetraethyl lead alone, or in high concentration in gasoline, ft is absorbed through the skin rapidly, its absorption is`retarded greatly by ft dilution in gasoline. I Indeed we have been unable to obtain avidence of appre- The results which have been obtained through attention to details in the use ft of special equipment, and through the inauguration and operation of suitable ft safety measures are described in Appendices 1 and 2 of this report. 0 017 3 9 8 ciable lead absorption through the skin of experimental animals after their pro longed exposure to concentrations of one part of tetraethyl lead per thousand parts of gasoline, by volume.2 The importance of this fact is twofold, not only does it indicate the improbability of the absorption of lead out of gasoline on the part of persons who come in contact with Ethyl Gasoline, but it also estab lishes the certainty that any minute amount of lead which might be absorbed would be unable to distribute itself in the flatty tissues and the nervous system in the manner characteristic of tetraethyl lead when absorbed at a rapid rate.2 An equally important effect of the dilution of tetraethyl lead with gasoline is the elimination of the danger of inhalation of lead, to a very large extent. The difference between the volatility of tetraethyl lead and the various gaso line bases with which it is mixed, is so great that approximately half the gasoline may be evaporated before lead can be found in the vapor.* It follows, from this fact, that the vapors rising from tanks containing Ethyl Gasoline do not contain appreciable amounts of lead. However, this does not mean that no tetraethyl lead is evaporated under any of the practical conditions of handling and use or spillage of Ethyl Gasoline. Although years of experience have not shown the existence of danger to the community in the use of Ethyl Gasoline, and although the qualities of the fuel, as described above, explain this result in a large measure, the possible lead exposure associated with the general dissemination of such a product may not be dismissed lightly. A full appreciation of the opportunities for exposure is required for an understanding of the problem which they provide for investi gation. ffe have found that no accumulation of lead occurs in rabbits as the result of months of exposure for several hours daily to suoh vapors, in experiments in which the gasoline vapors were sufficiently concentrated to maintain the animals in a state of mild intoxication with vertigo. KE 0017330 9 Ethyl Gasoline is handled at refineries, hulk storage plants, filling stations, and in public and private garages. It is transported from one to another of these sites in task ships, tank cars, tank trucks, barrels, and tins. In the United States and in Canada an overwhelming proportion of this motor fuel is dispensed through filling station pumps. In England a large amount of gaso line is distributed in two-gallon cans which are filled by essentially auto matic machines at refineries and at storage points. Large numbers of persons come In contact with Ethyl Gasoline to a greater or lesser degree through spill age, as an unavoidable result of the various methods of distribution. They also inhale vapors from tanks, hose lines and from surfaces on which the gasoline is spilled. At refinery loading racks, at filling stations and at other points where gasoline is handled regularly, the repeated spillage of Ethyl Gasoline may bring about the accumulation of higher boiling petroleum fractions, and of small amounts of tetraethyl lead, by reason of their absorption into wooden platforms, or other surface materials such as concrete, asphalt, gravel, cin ders or earth. Under these conditions some portion of the tetraethyl lead is evaporated slowly, and the remainder undergoes decomposition. In either case, opportunity for inhalation of lead on the part of persons in the vicinity may be provided, though, no doubt, most of the accumulations are dissipated by frequent hosing, or by rainfall. The sale of the gasoline to the consumer takes it into the province of the general public where some degree of exposure to skin contact and to vapors may occur. Of much more importance, however, is the appearance of a new 8et of conditions based upon the combustion of the fuel.' Tetraethyl lead is coaverted, thereby, into finely divided inorganic lead compounds (chiefly lead bromide}, which are deposited, in part, along the exhaust system, but which, 0therv?i3e, are discharged into the atmosphere with the exhaust, gases of the K 0017331 10 motor. The extent of the accumulation of exhaust gases from many automobiles in busy city streets, and especially in poorly ventilated areas where cars operate in considerable numbers, becomes a question of considerable importance. This aspect of the matter concerns the entire urban population, but it develops a special significance in the case of garage mechanics. Garages, in general, are poorly ventilated, pew of them, indeed, are equipped to maintain an adequate dilution of exhaust gp.ses, under the most favorable conditions, and, when doors and windows are closed, in cold weather, ventilation is often negligible. For this reason, through the winter months, many mechanics develop late afternoon headaches from the absorption of carbon monoxide. Their exposure to lead in the exhaust gas of automobiles burning Ethyl Gasoline is greater, therefore, than that of any other group of persons in the community. Further, the handling and the spillage of gasoline, the adjustment of carburetors, and the repair of other parts of the car often involve skin contact with Ethyl Gasoline and with lubricating oil which may contain minute amounts of tetraethyl lead. The spill age and evaporation of gasoline may leave behind the less volatile tetraethyl lead to be slowly volatilized at a later time, or to decompose, and by so doing to add to the lead dust in the garage. In the dismantling of motors the com bustion products of tetraethyl lead may be encountered by the mechanic, and although these cannot be absorbed through the skin, they may be a further means contaminating his hands, his clothing and his surroundings. We must regard these factors, as well as the deposited lead of the exhaust gases, as contribu tors to the accumulations of. lead dust within the garage although the amounts lead involved are probably not so great as those which originate from the repair of electrical storage batteries and the use of paints and solder in the Pepair of automobiles. Such lead dusts, from all sources, may be picked up by *lr currents and mixed into the air breathed by workmen. kj t ooi n ( Oo m &o 11 One further point must he considered in a complete analysis of the possibilities for general lead exposure in the use of gasoline containing lead. The deposition of lead compounds upon the highways, city streets,- in short, upon the surface of the earth - may conceivably influence the amount of lead breathed by animals and men, as well as the quantity incorporated in and deposited upon vegetation employed as food. The Distribution and Sale of Ethyl Gasoline in the United States. The qualitative character of the lead hazards derived from the use of Ethyl Gasoline is based upon the methods of its distribution and use. The general magnitude of these hazards is dependent upon the extent of the distribution of Ethyl Gasoline, the volume of consumption in a given area, and the period of time over which distribution and use have extended, these factors being modified to some extent by the variations in the lead concentration in gasoline, which have occurred in various sections of the country. Accordingly a complete representa tion of the situation requires some attention to these details. Ethyl Gasoline was distributed first in the early months of 1923 in Dayton, Ohio. A few months later it was on sale in Cincinnati and in the dis trict around Dayton and Cincinnati. Thence its use was extended to middlewestern and southern United States, into areas represented most satisfactorily ^7 the cities of Chicago, Detroit, St. Louis, Jacksonville, Atlanta and Savannah. The quantity of Ethyl Gasoline sold up to 1926 cannot be estimated accurately, but it was limited to this general area, and there was a steady increase in the volume of distribution during thib time except for a period of almost a year bginning in May, 1925. At this time Ethyl Gasoline was withdrawn from the ^rket pending an investigation of the United States Public Health Service, though for various reasons its use was not interrupted in certain areas in which tfl= -0017333 12 it first appeared on the market, - viz., in the cities of Dayton, Cincinnati, Savannah, Jacksonville and Atlanta and their vicinities. The resumption of dis tribution in 1926 resulted in the rapid expansion of the area over which the fuel was used. This expansion continued until Ethyl Gasoline had become avail able in all parts of the United States. Table I demonstrates the spread in the distribution in terms of the dates at which sale began in various cities of the United States. The duration of continuous distribution for these areas is also recorded up to the time of the observations which are to be described. The ap proximate quantities of Ethyl Gasoline sold during the years for which figures are available are shown in Table 2. (See Appendix 3 for data on the distribu tion of Ethyl Gasoline since 1929.) It should be noted that the general areas into which Ethyl Gasoline was first introduced have maintained the largest proportional and gross consumption. In the Ohio territory, where the greater part of the early investiga tion was carried out, the concentration of tetraethyl lead in gasoline up to 1926 was maintained at three cubic centimeters per gallon - approximately one part of tetraethyl lead in thirteen hundred parts of gasoline, by volume. In certain other areas, during thi3 same period, as low as two cubic centimeters was used. Since that time, the lead concentration has varied in accordance with the quantity required to bring the available gasoline base up to a defi nite standard of performance in a test engine, except that the amount intro duced has not exceeded three cubic centimeters of tetraethyl lead per gallon of gasoline. The average lead concentration by years for different regions of the country may be seen in Table 3. A brief study of the contents of these tables is sufficient to give a dear indication of the areas in which the greatest opportunities for lead -xpoaure have been provided. They also yield a graphic conception of the proJ)rtions of the problem which confronts us. k'g 0017334 TABLE 1 Period, of Distribution, of Ethyl Gasoline in Various American Cities Up to October 1929 13 Locality Dayton, Onio Cincinnati, Ohio Wheeling, 'A'. Va. Chicago, 111, Detroit, Mich. 3t. Louis, Mo, kansas City, Mo. Minneapolis, Minn. Milwaukee, Wi s. Saltimore, Md. Washington, D.C. San Antonio, Texas Savannah, Ga. Atlanta, Ga, Jacksonville, Fla. ITew Orleans, La, Cleveland, Ohio Philadelphia, Pa, Boston, Mass, ___ Denver, Colo. __^San Francisco, Cal, ____Dos Angeles, Cal. ^__Spokane, Wash. ^JThlsa, Okla. _____He* fork City Date of First Distribution February 1923 April 1923 Summer 1923 Autumn 19 23 Autumn 1923 Spring 1924- Spring 1924 Spring 1924 Spring 1924 Spring 1924 Spring 1924 Spring Autumn Autumn Autumn Summer Summer Suraaer Sumner Summer Summer Summer Summer 1924 1924 1924 1924 1926 1926 1926 1926 1926 1927 1927 1927 Summer Autumn 1927 1926 Interval of Discontinuance none none May 1925 to sumner 1926 May 1925 to Summer 1926 May 1925 to Sumner 1926 May 1925 to Summer 1926 May 1925 to Summer 1926 May 1925 to Sumner 1926 May 1925 to Summer 1926 May 1925 to Summer 1926 May 1925 to Summer 1926 May 1925 to Summer 1926 non none none none none none none none none none none none none Years of Continuous Distribution 6.7 6.5 3.2 3.2 3.2 3.2 3.2 3.2 3.2 3.2 3.2 3.2 5.0 5.0 5.0 3.2 3.2 3.2 3.2 2.2 2.2 2.2 2.2 2.2 1.0 0.58 ___ lO tIcSov*i KZ 0017335 Approxim ate Gross and C om parative Consum ption o f E th y l G asoline in V a rio u s Areas o f th e U n ite d From 1926 to O c to b o r o f 1929 o CO HE 0017330 P istribution Areas o f the United States ( Hew England S tates and New Y ork Pennsylvania A tlantic Coast States Ohio Kentucky, Georgia F lo rid a M ississippi Alabama Louisiana Arkansas Tennessee C e n tra l States Texas, Oklahoma Rocky Mt. States West Coast States TOTAL 19 26 M illio n s o f Percentage Gallons o f o f E th yl E th y l Gaso lin e . G a s o lin e to Total G a s o lin e . 1927 M illio n s o f Percentage Gallons o f o f E th yl E th y l Gaso G asoline lin e . to Total G a s o lin e . 1928 M illio n s o f Percentage Gallons of o f E th yl E th y l Gaso G asoline lin e . to T otal G a s o lin e . M G E li 6*6 6*0 0*16 <J\ to o iCnM 0.5 5.0 1 30.0 7.0 0.7 1 0*91 91*0 0*1 -------------------------------- 1 i 2.1 3.0 0.36 18.0 9*0 0*9 0*62 6*1 <* c\j 75.0 18.0 1.4 93.0 3.7 8*01 CO o CM to 0*0 0*0 0*0X1 in CO oo 0.2 0.5 O 8.0 2.9 0*91 0*8 i-4 O Oo 25.0 CO to 172.0 4.9 4.0 0.5 2.5 CO 10.0 3.1 4.3 30.0 2 .1 27.0 1.8 52.8 0.58 to <o fr- CM 2.8 547.0 5.0 TABLE 3 15 Average Tetraethyl Lead Content of Ethyl Gasoline in Various Areas of the United States from 1926 to 1929 Distribution Areas of United States New England States and New York Pennsylvania Atlantic Coast States Ohio Kentucky, Georgia Florida, Mississippi and Alabama Louisiana, Arkansas and Tennessee Central States Texas Oklahoma Bocky Mountain States West Coast States Average for united States Average Tetrslethyl Lead Content in Cubic Centimete rs per Gal. 1926 1927 1928 1929 1.4 1.2 1.7 0.9 1.0 0.9 1.4 1.4 1.3 r 1.4* i.i 1.0 1.6 1.2 1.7 0.6 1.6 1.7 2.0 0.7 1.6* 1.2 1.2 1.4 1.1 1.7 0.9 2.2 2.0 2.4 1.5 1.75 0.9 1.65 1.5 1.5 1.9 1.3 2.0 2.7 2.4 1.5 1.62 These figures are estimates only and may he somewhat in error. Kr 0017337 16. 2. Previous Investigations of Ethyl Gasoline in Relation to.the Public Health. It is not to be supposed that the possibilities of danger in the general use of Ethyl Gasoline have gone unnoticed, up to the present time. Oa the contrary, numerous experimental inquiries have been carried out. Thus the United States Bureau of Mines3 began an investigation of lead absorption from in halation of exhaust gas of automobiles employing Ethyl Gasoline as a fuel, in the autumn of 1923, before the new fuel had developed more than a localized dis tribution. The further investigations of the Bureau of Mines were extended to include other phases of the question. The united States Public Health Service4 studied the matter in 1925, and the Ministry of Health of Great Britain5 criti cally reviewed the previous experimental work and made farther contributions to it in 1928. Each of the latter two governmental agencies acted under the guidance of its own committee of experts appointed especially for that purpose. Our observations, beginning in 1924, have dealt with several aspects of the problem. First in 1925, and successively in 1926 and 1927, we investigated the lead exposure of persons engaged in the handling of Ethyl Gasoline and in the repair of automobiles using Ethyl Gasoline as a fuel. These have been de scribed in detailed reports5 to the United States Public Health Service, and to the Ethyl Gasoline Corporation, whose officials sponsored the work. 3. Investigations Carried out in 1929-30. A fourth field investigation is the subject of the paragraphs which to follow. I shall not discuss the methods or the results of the earlier experimental work carried out by ourselves or others, except to point out that Rne f them disclosed evidence of danger either to the health of persons en- HE 0017 3 3d gaged in the handling of Ethyl Gasoline or to that of the general public. In the li^it of the information which they have furnished, there can be little doubt that some of the hypothetical hazards which have been described, do not exist. However, I shall disregard such considerations for present purposes and 3hall confine myself to the presentation of observations which were made in the autumn and winter of 1929-30, employing certain items of our earlier data only for purposes of comparison. The object of these observations was to provide an answer to one question, is the magnitude of lead exposure arising from the com bined hazards of the use of Ethyl Gasoline such as t bring about appreciable lead absorption on the part of any group of individuals in the community? Accordingly, groups of subjects have been selected for detailed study of the effects of their occupation upon their health, and upon such physiological pro cesses as are specifically influenced by a significant increase in lead absorp tion. The Selection of Experimental Subjects. Table 4 shows the numbers and types of subjects selected, together with the locality in which they were employed. The three groups of workmen who experience all the means of lead exposure associated with the use of Ethyl Gaso line are adequately represented by fifty-six filling station attendants, fifty t&nk-truck handlers of such gasoline, and two hundred and one garage mechanics. The filling station attendants were chosen with attention to several otters; men who had been employed as subjects previously, who had been handlin8 Ethyl Gasoline for the longest period of time, who had handled gasoline conlining the highest concentrations of tetraethyl lead, and who handled the ^argeat amounts of Ethyl Gasoline daily, were especially desirable. Until May 1925 a small metering device containing a liter can of Ethyl Fluid was used 0017339 18 on filling station hose lines to treat gasoline with the lead mixture as re quired. This method of distribution brought about some degree of exposure to concentrated tetraethyl lead on the part of filling station employees. There fore, those subjects whose employment dates back to this period have had op portunities for the absorption of lead from this source. They were particularly favorable subjects for the determination of the maximal lead exposure associated with their occupation. It has been pointed out previously that in the cities of Dayton, Cincinnati, Savannah, Jacksonville and Atlanta there had been no in terruption in the distribution of Ethyl Gasoline since its introduction on the market. Furthermore the employment turnover of filling station attendants had been so slight that it was not difficult to find a satisfactory group of men who had dispensed Ethyl Gasoline since it was first marketed from their stations. The consumption of Ethyl Gasoline had been greatest in certain central states represented by the cities of Dayton, Cincinnati, Detroit, Chicago and St. Louis. In these cities individual attendants at certain well located fill ing stations had handled more Ethyl Gasoline than had men similarly employed in any other part of the country. The tank wagon handlers were selected on the basis of the severity and length of their exposure to Ethyl Gasoline. Twenty-seven of them had served as subjects for study in 1927. Thus a direct comparison of the results obtained on the two occasions was made possible. The garage mechanic group was made up of one hundred and nine persons wllo had been working on cars which used only Ethyl Gasoline, and an additional ain.ety_three who had been repairing cars of which a high percentage used such f&soline. Effort was made to find all the mechanics in the United States who experienced prolonged exposure in garages in which all- the cars had used Gasoline exclusively over a period of several years. Ten members of the K 0017340 19 group had been employed in a public service garage in Dayton, Ohio, in which Ethyl Gasoline had been the exclusive fuel from 1923 to the time of the present investigation. Thirty-nine subjects had had from three to six years of daily repair work on cars in which Ethyl Gasoline was the exclusive fuel. The entire group was composed of subjects who had been employed in continual repair work on fleets of cars. From every point of view the subjects selected for examination had the maximal opportunity for exposure to lead arising from their respective occupa tional relationships to Ethyl Gasoline. The garage mechanic group is entitled to special consideration since it is composed of men whose occupation combines all the potential lead exposures derived from Ethyl Gasoline in an intensified form, together with certain other lead exposures which are not related to Ethyl Gasoline. It is for this reason that it was expanded to a large number at the expense of the -less exposed groups. The barrel-fillers referred to in Table 4 were included among the subjects chosen for the present investigation for a specific reason which will appear later. The data are available through a fortunate combination of cir cumstances. Several years of observation of persons whose occupation involved considerable exposure to gasoline had aroused our interest in the influence of repeated and prolonged gasoline absorption. Accordingly search was made for a group of subjects whose exposure to gasoline was severe and uncomplicated by other factors. In the summer of 1928 such a group was found in a refinery in *hich large quantities of gasoline were put into fifty gallon barrels for ^Usportati on. The barrels were filled in a specially constructed room proTtded with forced ventilation. Despite the magnitude of ventilation the con futation of gasoline vapor was high enough to be immediately disturbing to 0&e who was not accustomed.to 3uch vapors. In addition, the skin, clothing We 0-017341 TABLE 4 Distribution of Subjects According to Occupation and. Locality 20 Locality Number of Filling Sta tion Atten dants Exposed to Ethyl Gas. #1 - #56 Cleveland Ohio Cincinnati Ohio 11 Dayton Ohio 11 Chicago Illinois 6 Detroit Michigan 1 St. Louis Missouri 11 Kansas City Missouri Minneapolis Minnesota Jacksonville Florida 6 Atlanta Georgia 10 Mi lwaukee Wisconsin Boston Mass ! Wheeling j ^__ W. Va. [ Hew fork 1 Saw fork | ^JTOTAL 56 Humber of Tank Wagon Handlers Exposed to Ethyl Gas. #101-#150 1 10 9 11 8 1 6 4 50 Number of Garage Mechanics. Exposed to Ethyl Gas. #301-#501 Number of Barrel Fillers Not Exposed to Ethyl Gasoline. #201 - #227 15 13 15 13 12 46 5 5 5 5 5 50 10 27 201 27 Number of Bartel Fillers Exposed to Ethyl Gasoline #251 - #272 22 22 Kff 0017342 21 I and shoes of the workmen were frequently and almost continuously soaked with i | gasoline. The barrels were lined up in a double row along corresponding rows \ I of pipe lines each of which was provided with an elbow, a flexible hose and a !| float valve. Each hose line with its valve was inserted into a drum, and the || valve was opened. Gasoline flowed in at considerable pressure until the level || of liquid in the drum released the valve, thus closing it. Occasionally the | I valve refused to work properly, at which time a stream of gasoline rose from | I the drum and thoroughly drenched any workmen in its immediate vicinity. I| The number of men engaged in filling ana handling the drums of gaso- | I line was small but the severity of exposure was such as to give excellent oppor- f I tunity for the detection of any effects which might result from gasoline absorp- I+ | I tion. These men were carefully examined in a manner which will be described I I later,and several types of laboratory data were obtained, including the lead iI ' content of the urine and faeces. (These latter data were obtained because of II our interest in the lead excretion of groups of workmen with no occupational 1I i.1 sxposure to lead compounds.) %C Shortly after these examinations had been completed the refinery in l I Question undertook the distribution of Ethyl Gasoline. The latter was handled manner described above for ordinary gasoline. Inasmuch as experimental % B 07idenee indicated that the hazards of lead absorption from skin contact and & Inhalation of vapor from gasoline containing tetraethyl lead were practically 1 ^eligible, no fears were entertained as to the consequences of the additional : ?ator of a low concentration of tetraethyl lead, nevertheless, this constituted ^ique situation from the point of view of severity of exposure. Therefore considered imperative to obtain information which would show whether or an appreciable lead absorption was occurring in the men. Accordingly, at ead of a period of six months, during which Ethyl Gasoline had been handled tf/T 0017343 dally in this manner, the workmen so employed were examined, and samples of their excreta were obtained for analysis. In this second group made up of twenty-two men, there were ten who had been included in the first set of ex aminations. Except in the case of the barrel-fillers, comparable groups of sub jects unexposed to the potential dangers of Ethyl Gasoline, were not obtained for study. At the time of the present study of filling station employees, tank wagon handlers of Ethyl Gasoline and garage mechanics, there was no area of the United States in which the selection of entirely unexposed subjects could be made with precision. The use of leaded gasoline had increased rapidly, so as to involve all parts of the country. Furthermore the employees of a large pro portion of the major gasoline distributing companies were handling Ethyl Gaso line. Therefore it was necessary to rely on information obtained prior to the general distribution of Ethyl Gasoline, for comparative data on similar groups of subjects independent of the factor of leaded gasoline. Fortunately, such 4ata were adequate. Furthermore, repeated observations had been made on the same individuals under conditions of continuous exposure. These successive findings furnish a means for the discovery of progressive effects of any type. of Study. Experimental studies on animals and men have established the exist- * 41100 of a relationship between the magnitude of lead exposure and absorption j ^ the rate of lead excretion, in that faecal excretion is a measure of inges ^0a on the day preceding the collection of the sample, while the urinary ex J. *?eti on indicates the magnitude of lead absorption. Data which substantiate 80 points are presented later in this report under heading "4. Investigations aned since 1930." Nevertheless, considering the importance of the matter 23 at issue, we have considered it desirable to leave no stone unturned which might yield additional information. Accordingly we have searched for clinical evidences of lead absorption with the same care that we have applied to the collection of accurate analytical data. The general clinical methods were simi lar to those employed by J. P. Leake^ and his associates and by ourselves in H other investigations of the same question. A comprehensive neurological examina tion constituted the only significant addition to the previous technique. Care was taken to obtain all the information possible from each sub ject, and to record such information in a uniform manner. For this reason cards for recording data were provided as reproduced below and the work was divided among four physicians each of whom carried out the same type of observations on each subject. So far as possible quantitative information was obtained in the physical examination, but without the subordination of clinical judgnent to the necessities of statistical comparability. Thus while it was recognized that a statistical study of all the data was desirable and necessary, sound clinical diagnostic methods as applied to individual cases were regarded as of greater te&portance, in determining whether or not any evidence of lead intoxication ki appeared among the subjects. As an example of this point of view, each I Object was tested for evidences of atrophy or muscular weakness by palpation lad by opposing the examiner's strength to that of the corresponding muscle of the subject. But for the purposes of statistical comparison of a ' * |.|dQgle neuro-nuscular factor, the grip was tested by a hand dynamometer. (The ^ instrument was employed throu^aout the tests.) Measurements of the blood pressure of each subject while seated, were with a standard manometric apparatus. KE 0017345 24 A. HISTORY SHEET Ho. Examiner's Initials Date Name Age Race Color Birthplace Marital Ages Children . Miscarriages Stage Besidance Other places lived in, with dates place of Employment Type of work (exact description of nature and conditions) Length of present employment and previous employment at same work Previous Occupations Pates Previous Lead Hazards Painting Plumbing Carriage, Auto or Car Type Casting Smelting or Refining "Treating" Refineries Storage Bat. Mfg. or Rep. Lead Burning Printing or Lithog. Mining Foil, Solder, Babbit, Mfg. Pates Previous Lead Hazards Pates Brass Pounding Soldering Enameling Paint Mfg. Pottery Glass Polishing Cut Glass White Lead Rubber Garage Telephone or Telegraph Rep. Automobile Oner Gasoline Used Repair Work Previous Illnesses with dates and exact descriptions (no leading questions) Tbc. Malaria Rheumatism Lues. Go. Scarlet Piph. Typhoid Tonsillitis Frequent Colds Convulsions Heart Pisease Asthma Significant Family History: Remarks: KE 0017346 A. HISTORY SHEET (Cont) Ho. Examiner's Initials Hate Sleep Hours in Bed. Breams Restful Bisturbed Bowel Movements Frequency Hour Tendency to Constipation Cathartics Tendency to Frequent Stools Teeth Brushing When Last Trip to Bentist Usual Weight Best Weight Recent Loss Weight (seasonal?) General Health Rate of Tiring Recent Change Headaches Time Eye Trouble (character and time of development) Taste in Mouth Character Time Pains in Joints Swelling of Joints Muscular Strength Cramps in Muscles Pains in Belly Character Frequency Appetite Bifferent Meals Bigestive Bisturbances Nausea or vomiting Skin Infection or Eruption General Hands Polyuria Hocturia Frequency Nervousness General Weakness * Other Complaints Right or Left Handed Loss of Strength in Arms or Legs at any time Shooting pains Numbness or tingling -'& Loss of Sensation KA 0017347 26 B. PHYSICAL EXAMIMTIOT SHBBT" lio. Examiner's Init. Date Age Height General Appearance nutrition Pulse Temperature Color of Skin (exact) Posture Uusculature Blood Pressure (seated) Condition of Skin Condition of Skin of Hands Cornea Sclera Pose Throat Glands Tonsils Mucous L'emhranes Ears (structure) Teeth Gums Pyorrhoea, lead Line (Appearance and Location) Heart Apex Hate After 25 hops 2 minutes after R.C.D. R.S.D. toags: 2.1. - H. L. L*lift B* L. L. Weight Cte3-t Diagnosis Spleen Genitalia i^?9r Extromiti 93 ^Stoai s and Remarks Kidneys Lower Extremities KS' 0017348 C. 1TEUR0L0GICAL EXAMimTICSI Examiner's Init. Cranial serves I Smell II Sight R - 15/ L - 15/ Condit ion Correction III, IV, VI Extrinsic Eye Muscles Pupils Visual Field V Motor Sensory ,rII Facies VIII Audition R L Equilibrium IX, X, XII Speech Swallowing XI ITeck Shoulders Reflexes Jongue tfpper Extremities Tonus Atrophy Ataxia Tremor Xuscular Power Dynamometer Stereognostic Splcritio Protopathic Kinaesthetic Thermal Vibratory Xsrve Trunk Tenderness *C7; r Extremities Reflexes Pharyngeal Biceps Triceps Radial Petellar Achilles Epigastric Abdominal Cremasteric Plantar Gait 27 KF - 0017349 D. LABORATORY SHEET Ho Examiner's Initials Date URIIIALYSIS: Quantity Sp.G. Reaction {Methyl Red) Altunin (Heller's) Heat and Acetic Sugar (Fehling* s) Acetone (Hitroprusside) Microscopic BLOOD: White Count Haenoglobin (Dare) Red Count Differential (100 cells): Poly. Heutrophiles Poly. Eosinophiles Poly. Basophiles Lymphocytes Endothelial Large Mononuclear Transitional Stippling per 50 fields Abnormal Polychronasia ^LYPIQAL EXAMIRATI CUT: Accurate statement of hours required for collection of: Urine Faeces Constipation Diarrhoea Cathartic (type) FAECES UR IRE dish dried faeces di3h ash dish dried faeces ash l6ad Mgs. Mgs./gram of ash Analysis Ho. Volume c.c. Lead Mgs. Mgs./liter Analysis Uo* HE 0017350 28 A fresh specimen of urine was obtained from each subject and examined at once for it3 reaction, the presence of albumin, and sugar. Microscopic examina tion of the urine and a test for acetone were carried out only when indicated by chemical abnormalities or by suggestive clinical findings* Erythrocyte, leucocyte and differential leucocyte counts were made as a routine procedure only on the barrel-filler group of subjects. Otherwise, such procedures were followed only when indicated for diagnostic purposes. Haemoglobin determinations were made on each subject by means of the bare haemoglobinoneter. A single instrument was employed for all observations, and all readings were made by the same observer. Blood smears were made on all subjects, and were examined for stippling of the erythrocytes by the method previously described. Samples of urine and faeces were obtained from the subjects for the determination of their lead content. The collection of these and the analyses ere carried out according to methods which we have described In an earlier re- port,0 in a few instances no samples were obtainable. A further small number f samples were lost in transit and in process of analysis. With these few oxceptions, the analytical results were obtained without difficulty. ^perimental Findings. Ho case of lead intoxication was found among the subjects. In fact, combination of symptoms and physical findings was suggestive of lead intoxisuch evidences of lead absorption as are common among lead workers were .^spicuously absent. Of special negative clinical importance were the complete :*5s0nc9 of lead line, the lack of significant microscopic blood changes ' `'Appling), and the striking infrequency of vague symptoms of ill health. : r these circumstances any evidences of significant lead absorption as a HB 0017351 3300,. consequence of exposure to Ethyl Gasoline must he sought in the data on the ex cretion of lead. The clinical and analytical data for the groups are presented in a series of tables, in -which the factors are set down in the exact manner of the statistical study except as otherwise noted. Table 5 shows the classification of the subjects according to the duration of their exposure to Ethyl Gasoline. One-half of the filling station attendants and a little less than half of the tank wagon handlers had been ex posed for five or more years, while sixty-nine percent of the garage mechanics had repaired cars which used Ethyl Gasoline over a period of three years or aore. Whether or not it has any bearing on the problem at issue, the oc currence of previous industrial lead exposure among the subjects may not be ignored. Information on this point obtained from the occupational histories is shown in Table 6. Here it may be seen that a large proportion of the sub jects had been employed in trades which involved some opportunity for lead absorption, prior to their exposure to Ethyl Gasoline. Hone of the garage meehanics may be regarded as free from the possibility of lead exposure in their Cccupation, apart from the factor of Ethyl Gasoline. However, it may be as- that few garage mechanics have more than a slight lead exposure in the ;?4rae of their normal day's work, since small jobs of soldering and painting, ;lfi<i the occasional repair of a storage battery have not produced a noticeable i * J*Tence of lead intoxication among garage mechanics. Cne tank wagon driver Insight garage mechanics had been employed at some previous time in hazardous ^ ti*a&Qg> ia which their exposure had not been severe either in quality or ^Uon. The distribution of the subjects according to age, seen in Table 7, KE 0017352 ZABLE 5 Distribution of Subjects According to Period of Esgposure to Ethyl Gasoline __,siiS3SSf" 31. Period of Exposure | in Years I 0.1-0.25 I 0.5 I1 I2 13 14 95 96 T02AL3 Pilling Station Attendants Number % 12 6 11 16 28 23 41 10 18 66 100 lanE Wagon Handlers Number i 12 48 48 19 38 16 32 6 12 50 100 Garage Mechanics Number $ 26 13 36 18 96 49 22 11 12 6 73 201 100 Barrel Pillers Exposed to Ethyl Gasoline Number % 4 18 18 82 22 100 KE 0017353 ,,** TABLE 6 32 Distribution of 3ubJeots According to History of Previous Exposure to Lead Other Than Ethyl Gasoline Description Filling Station Tank Wagon of Attendants Handlers Lead Exposure Number % Number .% None 20 36 18 36 Garage Mechanics Number % Barrel Fillers Not Exposed to Ethyl Gasoline Number 7> 15 55 t51 Questionable 8 14 10 20 30 15 6 30 Slight ^ Moderate 28 50 21 42 163 82 12 84 3 1 11 4 J*' TOTAL 56 100 60 100 201 100 27 100 Barrel Fillers Exposed to Ethyl Gasoline Number % 10 46 6 27 6 27 22 100 KB 0017354 a TABLE 7 Distribution of Subjects According to Age 33 A^e in Tsars 15-19 20-24 25-29 50-34 35-35 40-44 45-49 50-54 55-59 f 60-64 I 65-69 | _?otal billing Station Attendants lank Wagon Handlers Number % Number % 35 12 21 12 21 59 24 59 47 7 13 6 11 56 100 15 30 7 14 10 20 5 10 5 10 36 12 36 12 50 100 Oarage Mechanics Number 9 32 : 33 34 42 26 11 8 4 2 % 4 16 17 17 21 13 5 4 2 1 201 100 Barrel Billers Not Exposed to Ethyl Gasoline Number * Barrel Billers Exposed to Ethyl Gasoline Number 2 6 23 5 19 6 19 6 23 14 14 28 15 29 6 27 29 7 31 29 15 15 26 100 22 100 iiean 1 Probable B ^fror of | 'lean B Staaiard B^Wiatian 40.6 1.2 13.07 38.6 1.1 11.28 34.3 0.5 9.86 37.9 1.2 8.76 39.1 1.3 9.34 TABLE 8 Distribution of Subjects According to Certain Subjective Abnormalities 34, Type of Abnormality Hecent Loss of Weight Increased Tendency to Fatigue Frequent Headache Occasional Abdominal Cramp Occasional Digestive Disturbance Occasional Keuritic JR Symptoms m ?oor S General .jtjUalth. 56 Filling Station Attendants Humber % 36 12 6 10 24 35 35 50 `Tank Wagon Handlers Humber CL 24 12 24 24 24 201 Oarage Mechanics Humber % 74 84 31 15 12 6 42 73 11 27 Barrel Fillers Not Exposed to Ethyl Gasoline Humber QPl 27 27 14 14 22 Barrel Fillers Exposed to Ethyl Gasoline Humber * 15 15 15 15 k 0017856 & 35. TABLE 9 Distribution of Subjects According to Certain Objective Abnormalities Type of Abnormality UnderNutrition Pallor Irritation of Skin of Hands Lead Line Nerve Trunk Tenderness 1 Tremors [ Sensory 1 Diaturban[ oea K Sxtensor I Paresis I Atrophy of K Upper KxK trend, ties B Abnormalities B Visual B^tteld U'inary ^idlty B^mainuria Filling Station Tank; 'itagon Attendants Handlers Garage Mechanics Number % Number ct Number % 4 6 248 4 2 4 2 4 23 11 11 20 12 24 56 28 6 11 17 34 17 8 20 36 21 42 71 35 1 2 364 2 1 2 361 1 1 2 489 4 2 4 12 20 39 15 33 92 46 49 6 3 Barrel Fillers Not Exposed to Ethyl Gasoline Number % Barrel Fillers Exposed to Ethyl Gasoline Number % 4 15 2 10 8 30 2 10 16 60 12 54 3 11 1 5 8 39 9 41 2 10 15 2 10 1 4 16 73 KB 0017857 36 is significant only in that it demonstrates the inclusion of widely varying age groups among the subjects under investigation. Tables 8 and 9 represent the frequency of occurrence of certain sub jective and objective abnormalities which are indicative of the presence of low grade intoxication. Among the symptoms, attention should be called to the high incidence of headache among the garage mechanics. The histories clearly sug gested carbon monoxide absorption as the background of this complaint. Irrita tion of the skin of the hands due to frequent contact with petroleum products showed a high frequency of occurrence in all the groups. Pallor was Host promi nent in the garage mechanic group and in the barrel fillers not exposed to Ethyl Gasoline. The explanations of this circumstance in the latter group is un doubtedly found in the feet that this group was examined in the summer when the inhalation of gasoline vapor was at its height. These men showed a correlative ; diminution of haemoglobin and a high average stippling - further indications of Wood changes resulting from their exposure to gasoline. Comparison of the I retaining items with the results of similar observations on various groups of I Objects unexposed to Ethyl Gasoline fails to yield any significant informa l-ion. (of. Tables 19 and 20). I In Tables 10, 11, and 12, the findings as regards blood pressure, S-hemoglobin of the blood, and stippling of the erythrocytes are recorded, iro values were computed for the occurrence of stippling by reason of the high *'*0Portion of negative results. It may be seen from the tables that no sigB^icance may be attached to variation in these matters in relation to Ethyl B*8line exposure, since practically all the findings are within normal limits. M*'bbe case of the systolic blood pressure, which is used here only as a 9 `*5ral means of pointing out the probable existence of vascular disease, the readings are sharply correlated with age, and hence have no significance 0017358 .f-igt 37 Tha low results are of no greater frequency than la common among corresponding groups of presumably normal persons. The haemoglobin determinations show only a high frequency of low results among the barrel-fillers unexposed to Ethyl Gasoline, as previously pointed out. Likewise the only point of interest in Table 12 consists in the relatively high results among these same barrel fillers. Apparently, exposure to gasoline vapors may produce blood changes, including the appearance of stippling. Tables 13 and 14 record the observations on the strength of the grip of the left hand and right hand, respectively, of the subjects. The frequencies and the means do not show any very striking differences between the groups, ex cepting that the barrel fillers as a whole, gave a somewhat weaker response to the test. The facts obtained from the analysis of the excreta of the subjects presented in Tables 15, 16 and 17. A survey of the tabulated results shows that a few high results are scattered irregularly through the data. Where these occur in faecal samples it may be assumed that they have resulted either ;?on contamination of the sample or from the ingestion of unusual amounts of with food material, and that they have no necessary or probable relationto occupational lead exposure. Accordingly the inclusion of such findings *a the computation of mean values increases appreciably the probable error of Cleans. TTevertheless, such results have been recorded, and have been in*uded in the calculations unless otherwise specifically noted in the tables. a result has been excluded it has been for the obvious purpose of eli, * ^ing a finding which has no possible relation to the problem at issue. case of the urine samples, aberrant results are of rare occurrence, as 1. a "e expected. On the other hand, contamination of an occasional sample the process of collection is apparently unavoidable, despite the most KK 0017359 TABLE 10 Distribution of Subjects According to Systolic Blood Pressure 38. Blood Pressure Headings Filling Station Attendants Tant Wagon Handlers Garage ~ Mechanics Humber h Humber % Humber A Barrel Fillers Barrel Fillers Humber % Humber % 50-59 90-99 1Z ; 100-109 35 ; 110-119 10 18 ' 120-129 18 32 130-139 \; 140-149 9 16 7 12 ; 150-159 24 . 160-169 ] 170-179 12 i 180-169 i_ i Information 2 3 4 5 1 jstal 56 100 11 42 2 4 16 8 16 32 52 26 10 20 62 30 7 14 36 18 4 8 18 9 2452 3 642 4 7 8 5 1 2 24 21 4811 50 100 201 100 27 1 15 26 ' 30 18 4 7 5 7 4 4 1 100 22 5 22 32 18 18 5 100 l*^robable Error J* ^scd&rd aKuiation 130 .1 1 .7 17.86 130 .4 1 .9 19 .30 125. 7 -iO. 7 15.10 134. 3 1. 8 13. 59 129. L *2. 3 15.86 00173G0 *1 Ur & SABLE 11 39 Distribution of Subjects According to Haemoglobin in Blood ---- *Raemoglobinometer Reading (Dare) 60-67 6S - 75 76-63 84 - 61 1 92 - 96 jSo Information filling Station Attendants Number 4 % 15 27 21 37 15 27 59 Sank: Wagon Handlers Humber 1 4 12 27 5 1 * 2 8 24 54 10 2 Oarage Mechanics Humber 13 6 77 39 92 46 15 7 42 Barrel Fillers Not Exposed to Ethyl Oasoline Number % 9 33 12 44 4 15 14 14 Barrel Fillers Exposed to Ethyl Oasoline Number % 15 15 8 35 11 50 15 f- j total 56 100 50 100 201 100 27 100 22 100 S Ktan Jrobable error - aiQaa JBhtodard M'w*atioa- SO. 9* -0*67 7.39 85.0* 0.59 6.11 84.5* 0.24 5.09 All means calculated on a wider grouping of readings. 71.1* 0.92 6.98 83.3* 0.91 6.34 KX 0017861 TABLE 12 40 Distribution of Subjects According to Stippling of Erythrocytes im 1 I Number of Stippled Cells Per OU XI 61(18 10 Ii 1 2-5 1 6 -10 1 11 -20 M 21 -32 g Total Filling Station Attendants Number 36 6 6 3 3 2 56 7> 64 11 11 5 5 4 100 Tani Wagon Handlers Garage Mechanics Humber 33 8 5 2 1 1 % Number % 66 159 79 16 19 9 10 17 8 453 211 z Barrel Fillers Not Exposed to Ethyl Gasoline Number 7 % 26 14 6 22 3 11 4 15 6 22 50 100 201 100 27 100 Barrel Fillers Exposed to Ethyl Gasoline Number 21 % 95 15 22 100 Z9SiI00 oo i T 8 u S' 2ABIE 13 41 Distribution of Subjects According to Strength of Grip of left Hand. Hand Dynamometer Hilling Station Attendants Heading .. i ... 50-59 Humber <sl P -- 50-69 ... 70-79 12 7 12 80-39 59 90-99 7 12 - 100-109 10 18 110-119 24 J- 120-129 150-139 12 140-149 12 150-159 '- J - jj 160-169 So laforaation Jotal 22 56 39 100 Tank Wagon Handlers Garage Mechanica Numb er 2 2 Humber 44 24 5 248 3 6 30 13 26 47 6 12 42 2 4 20 7 14 25 5 245 121 2 a/ P 2 1 4 16 23 21 10 12 3 3 1 1 10 20 9 4 50 100 201 100 Barrel Fillers Hot Exposed to Ethyl Gasoline Number % 5 19 27 4 15 3 11 6 22 27 14 4 15 27 100 Barrel Fillers Exposed, to Ethyl Gasoline Number % 29 3 14 29 7 32 3 14 4 18 14 22 100 V-, i K Itn-.n ^4 - 4 S 6able B *fror of Uui k !{*odard fBvT^atloa 95 .0 1 .9 16 .63 101.5 2.4 22.75 102.9 0.9 19 .37 91.1 2.7 19.05 95.0 2.4 16. 51 HE 0017363 TABLE 14 Distribution of Subjects According to Strength of Grip of Eight Hand 42 Sand Dynamometer Heading Filling Station Attendants Number Of 50-59 60-69 70-79 80-69 35 90-99 8 14 100-109 48 110-119 7 12 120-129 S9 130-139 35 140-149 24 150-159 12 160-169 No Info rniation 23 41 Total 56 100 Tank Wagon Handlers Garage Mechanics Number $ Number % 11 2 432 4 894 6 12 29 14 7 14 40 20 5 10 26 14 6 12 33 16 5 10 22 11 2 4 19 10 2 473 1 21 1 10 20 9 4 50 100 201 100 Barrel Fillers Not Exposed to Ethyl Gasoline Number % 27 3 11 14 4 15 3 11 5 18 3 . 11 14 14 4 15 27 100 Barrel Fillers Exposed to Ethyl Gasoline Number 2 14 7 33 29 29 4 18 3 14 29 14 22 100 Mean Fro bable Error of Mean Standard Deviation 112.6 2.2 18.43 114.0 2.4 22.34 116.3 0.9 19.58 101.9 3.3 23.30 105.0 3.0 20.89 R 0017864 TABLE 15 Distribution of Subjects According to Lead Found in Faeces 43 milligrams of Lead Far Sample of faeces 0 -0.079 I 0.05-0.159 j 0.16-0.239 j 0.24-0.319 Filling Station Attendants dumber 6 5 12 4 % 11 9 21 7 J 0.32-0.399 1 0.40-0.479 1 0.46-0.559 1 0.56-0.639 8 2 2 1 14 4 4 2 0.64-0.719 0.72-0.799 O.SO-Q.879 1 2 0.66-0.959 0.96-1.039 0.04-1.119 _^1.12-1.199 <5 Bo , Information ^lotal 2* 13 56 4 22 100 ' ; Tank Wagon Handlers Humber 1 4 4 6 6 2 5 2 1 % 2 8 8 12 12 4 10 4 2 12 Garage Mechanics Barrel Fillers not Exposed to Ethyl Gasoline Humber % Humber 53 2 7 26 13 4 15 33 17 2 7 25 12 3 11 28 14 4 15 17 9 3 11 13 6 1 4 84 733 11 73 32 211 4 211 4 63 1* 2 17 34 50 100 6* 3 13 6 201 100 3* 27 11 100 J^san 0.258 0.360 S ffobable ^rror of +0.016 +0.023 3t&ndard #v5wiaticn 0.169 0.197 'Emitted in calculation of means. 0.379 +0.012 " 0.245 0.380 +0.037 0.266 Barrel Fillers Exposed to Ethyl Gasoline Humber % 29 9 40 5 22 15 29 15 15 1 5 22 100 0.268 + 0.024 0.160 0017865 TABLE 16 Distribution of Subjects According to Lead in Milligrams per Gram Ash of Faeces 44 Milligrams of Lead Per Gram of Ash 0.00-0.039 0.04-0.079 0.0S-0.119 0.02-0.159 0.16-0.199 0.20-0.239 0.24-0.279 0.26-0.319 0.32-0.359 0.36-0.399 0.40-0.439 0.44-0.479 Jl0.46-Q.519 J 0,65-0.599 3J>&4-0.679 j|Uo- + filling Station Attendants Number 10 14 9 4 2 1 1 1 % 18 24 16 8 4 2 2 2 1* 2 Sank Wagon Handlers Number % 24 16 32 48 36 36 12 12 12 12 1* 2 Garage Mechanics Number 5 != 2 51 25 54 27 36 16 18 9 84 42 42 11 Barrel Fillers Not Exposed to Ethyl Gasoline Number 1 * 4 9 33 7 26 3 11 27 14 14 Barrel Fillers ExpoBed to Ethyl Gasoline Number % 7 32 8 36 29 3 14 29 14 52 2 7 31 1* 1 reformation 13 22 17 34 13 6 1*^1 56 100 50 100 201 100 27 100 22 100 iBNable Of jWj^^rd j|r^iUoa o.oe7 *0.007 0.065 m Calculation of Mean. 0.120 0.123** 0.131 0.137 0.113 *0.014 0.115 0.004** 0.005 0.074** 0.100 0.014 0.106 0.007 0.052 Calculated after exclusion of three results over 0.64 milligrams. KE- 0017366 i SABLE 17 Distribution of Subjects According to Milligrams of Lead Per Liter of Urine 45. Milligrams of Lead Per Liter of Urine 0-0.039 billing Station Attendants Number 18 % 32 C. 04-0.079 : 0*08-0.119 0.12-0.159 ; 0.15-0.199 J 0.20-0.239 ; G.2.4---G.279 i. i 0.25-0.319 15 13 3 3 1 27 23 5 5 2 0.32-0.359 4 ' 0.36-0.399 1 j 0.40-0.439 | 0.44-0.479 '1 ^--*0.46-0.519 0.52- + 1 * '^^foraaticn ^otal 1** 2 56 2 4 100 -m Sank. Wagon Handlers Garage Mechanics Humber % Number % 11 22 45 22 18 36 76 38 4 6 34 17 1 2 16 8 1252 31 1 231 1 23 1 1211 11 11 11 1211 1** 2 3** 1 Barrel Fillers Not Exposed to Ethyl Gasoline Number % 6 22 16 60 5 18 10 20 8 4 50 100 201 100 27 100 1 ^babls ji ^tor of i* J^^tdard 0.071 to.005 0.050 0.089 to.Oil 0.099 0.066 0.004 0.079 9411 oalculated on a wider grouping of findings, ? '***01 uded in calculation of means. 0.058* 0.009 0.071 Barrel Fillers Exposed to Gasoline Number 8 % 36 10 45 29 15 15 22 100 0.052* 0.004 0.030 HE 0017367 iifiiiliiitenr-^ I careful instruction of the subjects. This is not remarkable when the ubiquity I of lead compounds is appreciated, and when the lack of understanding of chemical cleanliness on the part of the subjects is taken into account. The analytical results serve to classify the various groups of subjects S3 distinctly outside the hazardous lead trades. At first glance,, the mean Talues for the lead content of the faeces of filling station employees, tank wagon handlers and garage mechanics seem high, as compared to those in normal persons with no occupational lead exposure. On the other hand, the small group of barrel fillers who were not exposed to Ethyl Gasoline, and who had no other occupational lead exposure at the time of the examination, show similarly higfc. findings* Furthermore, when the faecal lead is expressed in quantitatively comparable terms, in milligrams per gram of ash, the apparently high results I039 their significance. Finally, for reasons which will appear later, it is Inpossible to draw exact conclusions as to the magnitude of lead absorption, from the results obtained and samples of faeces. Thus it is necessary to re sort to the study of the urinary excretion for such information. As judged by ftis standard, the groups fall into the category of persons lacking occupation- exposure to lead compounds. A special significance derives from the failure of the barrel fillers * show any increase in their lead excretion as a consequence of their exposure * Sthyl Gasoline. Fot only do the two groups fail to differentiate themselves ,rorn point of view of lead excretion, but it is equally true that no single dividual in the groups can be differentiated. Of the ten persons who were prior to exposure to Ethyl Gasoline, and again after six months exto Ethyl Gasoline, no one person shows an increase in his rate of lead ion. This can be interpreted only as meaning that there was no sig*'fi * 0a&t lead absorption as a consequence of this exposure. Thus, it seems 0017S68 47. quite clear, that the inability of animals to absorb measurable amounts of tetraethyl lead out of gasoline in dilute solution,2 (1 part per thousand by volume or less) is shared by man. Comparison of the Findings of 1929-50 with Results Obtained Earlier. In view of the important conclusions of the above paragraphs, indicat ing the completely negative character of the findings, it 1b proper to present observations of a strictly comparable character on groups of subjects similar to those employed in the present investigation, in every matter save that of ex posure to Ethyl Gasoline. Accordingly, Tables 18 to 26, inclusive show the re sults obtained in 1927, in the study of groups of persona who bad not been ex posed to the conditions associated with the use of Ethyl Gasoline. The medical student group is composed of members of a newly matriculated class. For the second group, filling station attendants and bulk handlers of ordinary gaso line are combined in order to make a large group for statistical purposes. Unfortunately, no analytical data are available in the case of the bulk handlers of gasoline, because of their unwillingness to cooperate in the col lection of samples. Therefore the analytical findings relate only to filling Nation attendants, as indicated in the tables. The control garage mechanic Eroup is made up of only a small number of men carefully selected in 1926 as Peking any exposure to Ethyl Gasoline. The rigid requirements in the latter ?egard introduced considerable difficulty into the problem of obtaining co operative subjects. ITo explanatory comments are required, since the tables present the Served facts adequately^, It should be pointed out that the observations orded in these tables were made by the same persons who collected the data fa ne exposed subjects previously described. The clinical methods employed in 0017369 48 the two instances were substantially the same, while the analytical methods were practically identical. Summary of_ Certain Findings in Present and Previous Investigation, Table 27 summarizes the mean values for all the groups of exposed and unexposed persons, in such matters as would seem to have special significance, (Since the frequencies of occurrence of stippling do not lend themselves to com putation of mean values, comparison of this important factor must be made from tbe tables of distribution.} Comparison of the means reveals a striking lack of statistical differentiation of the groups. The medical students show a significant difference in age, but in no other factor. The barrel fillers not exposed to Ethyl Gasoline show a significantly low haemoglobin content of heir blood, as previously pointed out. The mean lead content per sample of feeces also shows certain statistically significant variations within the groups, but no actual importance can be attributed to these differences in dew of the variability in the size of the faecal samples. When the latter kctor is corrected by expressing the lead in the faeces in relation to the Entity of ash, the variability of the groups becomes statistically insigdficant. E*V Influence of Previous Occupational Lead Exposure. It has been intimated previously that some significance may be at- pihed to the fact that a considerable number of the subjects had been exposed lead compounds in previous occupations. Likewise the handling of lead comQ(la other than leaded gasoline and its deposits on motor parts and else"`e' might be expected to have some influence upon the lead absorption of the mechanic. As a means of ascertaining the importance of these matters, Kfr 0017370 49 the analytical results derived from two small groups of persons whose occupa tional histories failed to give evidence of previous lead exposure, were subject ed to a study, Table 6 ha3 shown the distribution of the subjects as to previous occupational lead exposure. Table 28 presents the mean values for the lead ex cretion of these subjects as separate groups and in combination. The results are seen to be slightly lower, but no significant statistical differences have resulted from the exclusion of the previously exposed subjects. Considering the rate at which large quantities of lead have been shown to be eliminated from the body, the effects of previous slight or moderate exposure to lead, would not be expected to manifest themselves in an increased excretion after the lapse of years, nevertheless it is of some interest and importance to establish the facts in the matter. Lead Excretion in Relation to Length of Exposure to Ethyl Gasoline. It would appear that an examination into the relationship between length of service and lead excretion, might provide a means of ascertaining the significance of the lead exposure associated with the occupation of the garage mechanics. This was done first by studying the correlation between the period of continuous employment as mechanics and lead excretion, and them by a cor responding study of the length of exposure in repairing cars which used Ethyl Gasoline, as against lead excretion. The results of these attempted correla tions are shown in Table 29. There is a complete lack of correlation in either matter, prom these results one must conclude either' that the lead exposure associated with the occupation is insignificant, or that it is of such ir regular occurrence as to have no measurable time relationship. There remains one other means of examining the available data in search of evidences of lead absorption from the handling of Ethyl Gasoline. KE" 0017371 TABLE 18 Distribution According to Age of Groups of Subjects Not Exposed To Ethyl Gasoline, Examined in 1927 50. I Age In [ Years I 15-19 | 20-24 [ 25-29 [ 20-34 25-39 1 40-44 j 45-49 50-54 55-59 60-64 65-69 70-74 _ Total Medical Students Number 11 51 9 % 15 72 13 71 100 Pilling Station Attendants and Tank Wagon Handlers Number % 11 18 16 23 20 16 14 11 10 13 11 10 9 10 9 54 44 33 114 100 Garage Mechanics Number 2 2 ' 12 12 2 4 1 % 6 6 34 34 6 11 3 35 100 Mean Probable Error of Mean f- Standard _Deviation 22.3 0.2 2.3 37.5 0.8 12.54 31.2 0.8 6.69 K& 0017372 TABLE 19 Distribution According to Certain Subjective Abnormalities of Groups of Subjects Not Exposed to Ethyl Gasoline - Esamined in 1927. 51 1 Type 1 of I Abnormality [ Recent loss I of Weight | Increased I leniency to fatigue Occasional Headache i Occasional Abdominal Cramp Occasional Digestive Disturbance Occasional Neuritio Symptoms Poor General __ Health 71 Medical Students Number % 7 10 9 13 15 21 11 11 23 69 Filling Station Attendants Number % 11 12 17 17 25 23 8 12 57 34 42 Tank Wagon Handlers Number % 25 5 12 7 17 10 24 25 00 35 Garage Mechanics Number % 5 14 5 14 18 51 4 12 13 Kg' 0017373 SABLE 20 Distribution According to Certain Objective Abnormalities of Groups of Subjects Not Exposed to Ethyl Gasoline - Examined in 1927 52 Sype of Abnormality Uzdernutrition Pallor Irritation of Srtin of Hand s lead line $r amors Sensory Disturbances * / Urinary j Aoidity ? a Uou^inuria 71 'Medical Students Number 7 10 11 23 34 7 10 11 69 Filling Station Attendants Number % 42 Tank Wagon Handlers Number % 13 19 34 35 Garage Mechanics Number <*? 23 9 13 4 10 9 13 25 3 4 16 38 3 4 37 4 11 39 13 8 23 39 1 0017374 TABLE 22 54 Distribution According to Haemoglobin of Blood of Groups of Subjects Hot Exposed to Ethyl Gasoline, Examined in 1927 Kaemoglooinometer Heading (Dare) 60-64 65-69 70-74 75-79 80-84 85-89 90-94 95-99 100-104 105-109 Total Medical Students Humber 1 1 % 1 1 34 10 15 21 30 17 25 11 16 57 11 70 100 Filling Station Attendants and Tani Wagon Handlers Humber % 11 98 12 11 17 16 43 40 15 14 98 22 Garage Mechanics Humber % 13 26 6 18 12 35 10 29 39 108 100 34 100 HE 0017876 2ABIE 23 Distribution According to Stippling of Brythrocytes of Groups of Subjects Not Exposed to Ethyl Gasoline, Examined in 1927. 55 Number of Stippled Cells .Per 50 Fields 0 1 2-5 6-10 11-20 21-32 Total Medical Students Number 58 5 7 1 % 82 7 10 1 71 100 Filling Station Attendants and Tank. Wagon Handlers Number 72 20 14 7 % 63 18 12 6 Garage Mechanics Number 22 6 6 1 % 63 17 17 3 11 114 100 35 100 TABLE 24 Distribution According to Lead Found in Faeces of Groups of Subjects Hot Exposed to Ethyl Gasoline. Examined in 1927 56. I Milligrams of Lead I Per Sample of I Faeces 1 0 - 0.079 O.OS - 0.159 0.16 - 0.239 0.24 - 0.319 | 0.32 - 0.399 > 0.40 - 0.4:79 0.48 - 0.559 0.56 - 0.639 0 64 -- 0*719 0.72 - 0.799 0.30 - 0.679 0.8b - 0.959 0.96 - 1.039 1.04 - 1.119 1.12 - 1.199 1.20 - _ Total Medical Students Eumber 17 15 19 6 3 2 2 1 1 % 25 22 27 9 5 3 5 i i 1i 1i 1i 1i 70 100 Filling Station Attendants Humber % 14 20 14 20 18 25 7 10 7 10 66 11 11 11 3* 4 72 100 Garage Mechanics Humber 5 7 2 2 3 2 1 % 19 27 6 8 11 6 4 14 3* 11 26 100 Mean 0.232 Brobable Error of Mean -0.019 Standard Deviation -0.0236 Secluded in calculation of means* 0.197 -0.013 -0.159 0.235 -0.029 -0.205 K 0017878 i IABLE 25 Distribution According to Milligrams of lead. Per Gram Asia of Faeces of Groups of Subjects Not Exposed to Bthyl Gasoline, Examined in 1927 Milligrams of Lead Per Gram of Ash 0 - 0.049 0.05 - 0.099 * i 0.10-0.149 0.15 - 0.199 0.20 - 0.249 0.25 - 0.299 I 0.30 - 0.349 0.35 - 0.399 I 0.40 - 0.449 j 0.55 - 0.599 0.65 - 0.699 i 1.50-4i Petal 3 Medical Students Number 29 16 9 3 1 % 48 27 15 5# 2- 1 21 2- 60 100 Filling Station Attendants Number 29 26 8 4 % 41 31 11 6 11 11 11 2** 71 2 100 Garage Mechanics Number 12 6 1 2 1 1 1 % 46 23 48 444- 28 26 100 3_ A iri^an Probable Brror of ^ il02.J1 Standard Deviation 0.079* 0.006 0.094 0.077** 0.006 0.071 Mean. Calculated on a wider grouping of Findings. "Bxoluded in Calculation of Mean. Calculated after exclusion of two results over 0.65 milligrams. 0.085 0.131 0.012 0.023 0.085 0.177 0017879 TABLE 26 Distribution According to Milligrams of Lead. Per Liter of Urine of Groups of Subjects Hot Exposed to Ethyl Gasoline, Examined in 1927 58 Milligrams of Lead Per Liter of Urine 0 - 0.029 0.03 - 0.059 0.06 - 0.069 0.09 - 0.119 0.12 - 0.149 0.15 - 0.179 0.16 - 0.209 0.21 - 0.239 0.24 - 0.269 0.27 - 0.299 0.45 - 0.479 0.54 - 0.569 0.66 - 0.689 1.00 - 4Total i Medical Students Humber 11 22 16 10 1 1 1 1 % 17 34 25 15 1+ 1+ 14 1+ 1 1+ 1* 1 + 65 100 Pilling Station Attendants Humber 11 20 17 6 4 3 5 % 15 28 24 8 6 4 7 1 14 1* 1 + 1* 1 + 3* 4 72 100 Garage Mechani os Humber 8 4 5 2 5 % 431 15 19 ' J 8 19 14 1* 4 J|| 26 100 (H m |__ Mean 1 Probable Error of I Mean 0.078 0.007 Substandard Deviation 0.089 "Excluded in calculation of means. 0.081 0.006 0.069 0.077 0.008 0.059 KE- 0017880 59 Among the subjects studied in 1929, there were twenty-six filling station atten dants, and twenty-four tank wagon handlers who had been employed as subjects in 1927, Presumably, if their occupation contains a significant lead hazard they should show some evidence of change in lead excretion after two years. The findings for the two years, as regards lead excretion, are shown in Tables 30, 31, and 32. The mean values are summarized in Table 33. It may be seen that no statistically valid difference is demonstrable. 4. investigations Continued Since 1930, Reference has been made to the fact that the faecal output of lead is determined largely by the rate of lead ingestion. Previous observations^ have shown that under conditions which permit the inhalation of finely divided lead compounds, in the dusty lead trades, the quantity of lead in faecal samples is indicative of the magnitude of the lead exposure. It must not be supposed that such alimentary lead is due to lead absorption and a resultant lead excretion. On the contrary, it is chiefly the result of swallowing lead with the secretions from the upper respiratory tract. It is clear, therefore, that in the lead trades, the lead content of the faeces fails to yield information as to lead a absorption. This is equally true in the case of persons outside the lead trades. Here also, the faecal excretion is a measure of the ingestion of lead 'dth food materials. The greater proportion of such ingested lead passes through the alimentary tract unabsorbed. It is not within the scope of this report to present the experimental Mdence which has established these facts, nevertheless, one series of ob servations which illustrate the facts may be described on account of its direct Nation to the main problem of this report. - K 0017881 60. Vl 0 CO G0 cr> 0 r-3 e& 33 CO ft 60 a ^4 <D i a H> | H co ro oo ^1 'CJ r- U3 O O <D q F4 i <0 to 8 IQ IN CM to 8 CM CM rH O o8 OO + h m 58 -H CD H CO rH oo oo -H CO IN O oo oo -H pp 4 o8 oo +1 00 <D in o oo # CM m o oo HI o X w 3G cj to p o G P *0 rQ o3 7* co GJ O SO CO 01 C' oG o 3ccoo 0a1 o G -t-H ^G G 2> ou HO 4 H G O^ nP PG CQ 3 *3 *D 01 ^o .O H 0) o ,) ** n 3M 5 *j ^ cO ,, n v, 0 rC CO CO to *4 a_ S G3 o? o P G <V O <0 s ** 111 fi P( H o CO IN o oo oo +i 0J a60- V| fHl r6c-0li O 0) 01 rt H ^ CD & O d t c d >-} 1-1 CD Cn c m <d tO r-1 CM o & ow rH 60 60 S O "H S 'd (u a) d a) W CD O CO H 'CJ o o 1--4 CQ o *13 --g a rH 3 P O CO .* tfl P 03 p >-. ** CD co fli -- CD 00 3 A rH G G fl> a) ^0>H *4 to c m CM Q CM -H r**. <0 in o oO oo -H CO O oo oo O 4* CM rH rH O rH tO CO CM rH O OO f* rH in CO o rH O * +? fc 4 CO rH rH O o+<p to t*. rf--H1 rV> - 0 00 H is. to CD rH rH O OO CO CO to rH CM O oo +1 o to O CM to o in a> to CM CM CD CM IN rH to O 4? 85 to o oo CO CO CM CM O 4? o to to CO E*CD <0 oo CO CD o to in o CO +1 O IN * CO Q CO -H tO CM ^O CO -H CM I CD > !+? to (D to o CD Hi c m in CO rH to -H rH in 8^ H* a> 8-fT CO to CD rH CM HI IN IN mo CM -H to CO H4 rH tO -H rH tO (D CM CM HI LO CO E- o tO -H CO CM O rH -H 8 CM rH CO rH O to-fT to in 5? o to H CD CM IN rH tO-H rH tO CD r-' to -H O 0 *~i 10 Ps H O c? O t -3 01 01 3 p CO CO c- 4-> CM G 0 a> CD 0 4* G rH T3 <-- 3 '3 rH G 4-> <I> O r4 CO a) CQ Oa rH pi 0 Q> a) H G 0 rH *r 1 *- 8 T3 p G 3 0 4-> X '^4 wM TJ 1 0) GXG O a w rH --t cH 0 E 4^ &o 4-> 3 CTj a O X 4-> M w CO 80 O Q> d u + G IN G 3 a> CM f--4 H rH *3 rH CD rH '3 <D O rH rH 'O G <0 CO ft 3G CD w O CO G Pi r*y H ^3 cy Q> 03 G CD G O rH CM O & rH CD rH X O #H +> ta CO CD aj G 4-> CO O rH CO 4-> G rH fu) a >> a> G 'G G H G rH rH 03 cq P rH 4-> 3 rH -P 0 X (H -p w G 3 a> rH rH G '3 >> rH G 3 <P a G wM X cq 0O 0 -P 0. bQ G '3 G CD iH CM CO rH 0% rX O O rH rt3G Pi (0 X G EH M G5 H CO O rH O G P 3 IN CM CD G rH rG *3 rH G O O rH 03 CO O G 'XS Pi O <D X G bD rH p cd a G p rC G G 0P X CD M sq 3 CO IH 0 0 > P p rG a GP G GW X pq O0 Q p > *3 G CD CM CO rH <D G 0 O rH P pi 01 G KG G CJ cq O p 01 O UP G p H 3 rH r--i <l O *r4 03 Ph O G Pi CJ HH pq iH HD upG G 0P CQ p ; W 03 GG ^4 H H rH O O p P co (* G 3 c5 H <0 rH G O > frG rG G MP CQ pq w Ke o 7882 Mean Values of lead in Faeces and Urine of Filling Station Atten dants and lank Wagon Handlers, Exposed to Ethyl Gasoline, Exclud ing All Besults Obtained on Persons With Other Industrial Exposure to lead Compounds, Lead in Milligrams In Single Sample of Faeces Lead in Milligrams Per Gram Ash in Faeces Lead in Milligrams Per Liter of Urine -lumber of Subjects Filling Station At t endant s Exposed to Ethyl Gasoline 0.338 0.043 lank Wagon Handlers Exposed to Ethyl Gasoline 0.277 0.035 0.069 0.009 0.116 0.024 0.063 i 0.009 19 0.063 i 0.010 15 Combined Filling Station Attendants and 'lank Wagon Handlers 0.336 0.030 0.086 i 0.011 0.065 0.007 34 - 0017883 TABLE 29 Showing Lach of Correlation Between Duration of Eaployment of Garage Mechanics and. Lead Excretion, and Duration of Expo sure to Ethyl Gasoline and Lead Excretion. a 62. Factors Correlated Length of Continuous Service as Garage Mechanic with Lead in Faeces in Milligrams per Gram of Ash, Length of Continuous Service as Garage Mechanic with Lead in Urine in Milligrams per Liter Length of Exposure to Ethyl Gasoline as Garage Mechanic Uith Lead in Faeces in Milligrams per Gram of Ash Length of Exposure to Ethyl Gasoline as Garage Mechanic 77ith Lead in Urine in Milligrams per Liter Correlation Coefficients + 0.017 0.056 +0.023 0.055 +0.223 0.099 +0.243 0.099 - K 0017884 TABLE 30 Distribution of Identical Subjects For the Years 1927 and 1929 According to Milligrams of Lead Found in Faeces. 63. Milligrams of Lead 3M Per Sample of Faeces |H 0 - 0.079 9T C.CS - 0.159 J 0.16 - 0.239 M 0.24 - 0.319 is 0.32 - 0.399 9 0.40 - 0.479 U 0.48 - 0.559 1 0.56 - 0.639 9 0.64 - 0.719 I 0.72 - 0.799 1 0.80 - 0.879 I 0.88 - 0.959 [ 0.96 - 1.039 I 1.83 5.10 L Total Filling .Station Attendants Exposed to Ethyl Gasoline 1927 Humber % 15 6 30 2 10. 1929 Humber % 3 15 3 15 8 40 3 15 2 10 3 15 15 15 15 2 10 15 15 1* 5 1* 5 20 100 20 100 Tank Wagon Handlers Exposed to Ethyl Gasoline 1927 Humber % 1929 Humber $ 2 12 +3 17 2 12 + +4 23 3 17 + +3 17 3 17 62 12 1 + +3 17 3 17 16 62 12 1 61** 17 100 17 100 .. _ Mean 0.280 0. 236 0.308 Probable Error of Kean 0.030 0. 023 ^ Standard Deviation 0.187 _ _ _ _ _ _ _ _ _ Qj l ISl 3_ _ _ _ _ _ _ _ _ Excluded in calculation of mean. 0.025 Q..15Q_______ With exclusion of single high result, the mean becomes 0.365 0.028 ! 0.402** 0.036 i] J0.218_____ j KE 0017885 TABLE 31 64, Distribution of Identical Subjects for the Years 1927 and 1929 According to Milligrams of Lead Per Gram Ash in the Faeces Milligrams of Lead Per Gran of Ash Filling Station Attendants Exposed to Ethyl Gasoline 1927 Number 1929 Number 4. Tank Wagon Handlers Exposed to Ethyl Gasoline 1927 1929 Number Number - 0.039 10 41 - 0.079 25 35 23+ 12 - 0.119 25 30 30 17 - 0.159 15 15 23 + 12 0.199 17 0.20 - 0.239 ). 24 - 0.273 0.2 = 0.319 0.32 - 0.359 0.36 - 0.399 0.40 - 0.439 0.44 - 0.479 0.57 0.64 1* 1** A 1.36 -ft Total 20 100 20 -10SL _UL ...lQQ _1Z_ ...10Q_ Mean Probable Error of Mean ^ Standard Deviation 0.118 -0.015 0.093 0.106 0.009 0.058 0.109 0*008 0.047 0.142** 0.019 ________ 0.117______-- Excluded in calculation of mean. `With exclusion of single high result the mean becomes 0.118 - 0.010 X 0017836 TABLE 32 Distribution of Identical Subjects for the Years 1927 and 1929 According to Milligram of Lead Per Liter of Urine 65. Milligram of Lead Per Liter of Urine A 1 - -IV ' 1 ' i 0 - 0.039 0.04 - 0.079 C.03 - 0.119 0.12 - 0.159 5.16 - 0.199 0.20 - 0.239 0.24 - 0.279 5.28 - 0.319 5.32 - 0.359 5.36 - 0.399 0.40 - 0.439 5.58 0.37 1.00 4.00 - + Total Filling Station Attendants Exposed to .Ethyl Gasoline 1927 1929 Number Humber 11 2735 27- 23 35 11 26 100 26 100 Tank Wagon Handlers Exposed to .Ethyl Gasoline 1927 Humber 1929 Humber 25 10 42 11 46 21 11 + 4+ 4+ 4+ 4+- 4+ 4+ 4+ 4+ 4 + 2* 8 + 24 100 24 100 Mean Probable Error of Mean Standard Deviation 0.142 0.024 0.180 0.111 0.025 0.188 0.129 0.015 0.106 Excluded in calculation of mean **Mean drops to 0.083 - 0.11 when one result of 0.87 milligrams is excluded. 0.115*" 0.024 0.173 0017887 TABLE 33 Summary of Kean Values of Lead Pound In Samples of Faeces, of Lead In Milligrams per Gram of Ash in Faeces, and of Lead in Milligrams Per Liter of Urine for Identical Subjects Examined in 1927 and 1929. 66 Filling Station Attendants Exposed to Ethyl Gasoline 1927 1929 M Lead in Milligrams in Single Sample of Faeces 0.280 *0,030 0.236 0.023 lead in Milligrams Per 9 Gram Asb in Faeces 0.118 0.015 0.1C6 0.009 H Lead in Milligrams per 9 Liter of Urine 0.142 0.111 0.024 0.025 M Lumber of Subjects 26 26 Tank Wagon Handlers Exposed to Ethyl Gasoline 1927 1929 0.308 0.025 0.402 0.036 Combined Filling Station Attendants and Tank Wagon Handlers 1927 1929 0.294 0.019 0.312 0.022 0.109 0.008 0.142 0.019 0.114 0.008 0.124 0.011 0.129 0.015 0.115 0.024 0.136 0.015 0.113 0.017 24 24 50 50 $ } i ] i - Hi 0017888 WB& 67. lead Exposure in the Handling of Ethyl Gasoline, Early in 1931 v/e made U3e of a new method of approach to the problem of lead absorption from exposure to Ethyl Gasoline. Having recognized the fac tor of lead ingestion with food, it became impossible to ignore it in further experimentation. Accordingly, through suitable arrangement with a gasoline distributing company, we were able to obtain two healthy young men for observa tion, with the understanding that they would be employed as filling station at tendants at the conclusion of certain preliminary studies. The two subjects had had no previous experience in the handling of gasoline, nor had they en gaged in the repair of automobiles. They had had no occupational exposure to I lead compounds. In fact, they had but recently finished school and were seek ing steady employment for the first time. Physical examination showed them to be in good health. They were intelligent and cooperative. I For four months these subjects were kept under observation at the -' A laboratory. During this period a duplicate sample of every article of food 1 4 and drink consumed was provided by each subject. Such items were combined into twenty-four hour composite samples, and were stored in chemically clean containers until they could be analyzed. Each subject also collected twentyfour hour samples of his faeces and forty-eight hour and seventy-two hour -i samples of his urine. (The number of samples of each week were divided into two forty-eight hour samples and one seventy-two hour sample.) At the end of the four month period, the .men were employed at filling stations, where they engaged in the usual routine of their occupation. The stations at which 3 i j they were employed were large, and were so situated as to serve a large clientele. Each man was employed at three different stations, at each of which the sale of Ethyl Gasoline constituted not less than thirty-five per cent of the total gasoline business. Every effort was made to see that a K 0017889 68 representative Ethyl Gasoline exposure was provided. Ho unusual precautions were taken against skin contact with gasoline, greases, or discarded crank-case oil. As a means of avoiding contamination of the samples for analysis, the men were advised to wash their hands before handling the containers. Such samples were collected in the manner previously described. The observations were con tinued for another four months period. The results of these observations are shown in Tables 34 to 39 inclu sive. The analyses of the faecal samples of one subject, and of the food samples of both, for the period of exposure have not been completed at present but the available results are sufficient for present purposes. If attention is directed first to the data of the control period it nay be seen that the mean daily lead content of the food of the subjects is almost equivalent to the mean daily faecal excretion. When the minute daily output of lead in the urine is appreciated it is clear that the lead in the faeces is almost wholly due to the daily ingestion of fbod which contains lead. Moreover, there is a wide variation in the daily intake of lead, in correspond ence v/ith the variation in the daily excretion of lead in the faeces. The recognition of these facts carries with it the certainty that the faecal lead cannot be regarded as a suitable criterion of the rate of lead excretion from the body tissues. Comparison of the findings of the control period with those of the period of exposure to Ethyl Gasoline discloses the fact that no evidence of appreciable occupational lead exposure or lead absorption can be found. It is apparent that the exposure to lead associated with the daily dispensing of Ethyl Gasoline, and v^ith the inhalation of the exhaust gases of the automobiles of the numerous patrons of a large filling station, is so slight that it cannot be measured. K 0017890 ^? TABLE 3k 69. Distribution of the Daily Food Samples of Two Normal Subjects, During a Control Period of Observation, According to Lead Content lajilligrsms of Lead M) -o.ol+ Sj,05-0.09 Suo-o.iii 9 3.15-0.19 83.20-0.2l+ 8d.25-o .29 80.30-0.31+ Io.35-o.39 | 0,1+0-OJ+I+ i \ 0.1+5-O.1+9 1 1 0.50-0.51+ 0.55-0.59 0.60-0.61+ Jj3.65-0.69 1 0.70-0.71+ |.Iotal Subject H 17 29 23 lit12 6 1 2 1 h 1 1 111 Subject M 13 23 21 17 17 7 5 2 2 2 2 111 Both Subjeots _22_______________ _ 52 1it 31 29 13 6 h 3. 2 6 1 1 222 fjlean Probable Error of +J-ean J Standard ^Deviation 0.155 0.008 to.132 0.168 0.007 0.113 0.161 "0.006 0.123 K 0017891 TABUS 35 Distribution of Daily Faeoal Samples of Two Normal Subjeots During a Control Period of Observation, Acoording to Lead Content 70 Wm Milligrams of Lead iH o -0.07 o.os-0.15 'H 0.16-0.23 31 0.24-0.31 IB 0.32-0.39 11 0.40-0.47 B 0.48-0.55 | '1 0.56-0.63 1 0.64-0.71 3 O.72-O.79 1 0.80-0.87 1 0.33-0.95 1 O.96- %_ Totals Subject H 17 30 28 20 13 5 7 1 1 1 123 Subject M 38 19 28 15 h 9 8 1 1 2 1 1 127 Both Subjeots 55 h9 56 35 17 14 15 2 2 2 1 2 250 I * C Moan -i 7 Probable Error of _ Mean Standard _ Deviation 0.239 io.013 i0.221 0.220 to.012 -0.194 OJ 1 O| 10.008 to.197 K 0017892 "aHji TABLE 36 Distribution of Porty-eight-hour ana Seventy-two-hour Samples of Urine of Two normal Subjects, During a Control Period of Observa tion to Ethyl Gasoline, According to Lead Content. 71 Milligrams of Lead 0.01 0.02 0.03 0.01+ 0.03 o.o6 0.07 0.08 0.09 0.10 0.11 0.12 0.13 o.H+ 0.15 0.16 0.17 0.18 Totals Subject H 1+8 Hours ______72 Hours 11 36 18 Subject M 1+8 Hour a 72 Hours 36 18 .'ean Probable Error of Mean Standard Deviation Average for 2h Hours 0.053 0.071 to.005 IO.OI4I+ 0.025 0.009 10.055 o.o6t+ 0.097 -0.00I+ to.032 0.032 to,008 *0.051____. `i I ",T1; K 0017883 ' '*9J '\3 '2 :" : i l j j ! 1 t 1 5 3 i : TABLE 37 Distribution of the Daily Faeoal Samples of One Normal Subject Lead Content Milligrams of Lead 0 -0.07 0.08-0.15 0.16-0.23 0.24-0.31 0.32-0.39 0.ko-aJ.fi 0.48-0.55 0.56-0.63 0.6U-0.71 0.72-0.79 0.80-0.87 0.88-0.95 0.96-1.03 1.04-1.11 Totals Subject M 38 21 12 7 4 2 4 1 1 1 122 Mean Probable Error of Mean Standard Deviation 0.190 0.011 0.179 72. _ K 0017894 TABLE ?8 Distribution of Forty-eight-hour and Seventy-two-hour Samples of Urine of Two Normal Subjects, During a Period of Exposure to Ethyl Gasoline, Aocording to Lead Content 73. Milligrams of Lead Subject H l\8 Hours 72 Hours Subject M lj.8 Hours ______72 Hours 0.01 0.02 0.03 O.Ol* 0.05 0.06 0.07 0.08 0.09 I~ 0.10 0.11 0.12 0.13 o.iU Totals 3h 18 3U 18 Mean Probable Error of Mean Standard Deviation Average for 21; Havre 0.061 to.ooU *0.039 0.079 to.006 *0.033 0.028 0.051 *o,,oo3 *0.029 0.081 20.006 to.oUi 0.026 Kt 0017895  0) A, .9 0 CO to t- Fi > 3CuO 02 o 02 o Cel O ooo o 8p< 'O * FP H to C\2 02 to 00 02 do o F. o o o Poo o o (1) o V2 P O >> 0 Vi r-1 O H ,Q cd Fl T3 O CO O H a o p. H & O EH Pi TP y * o to h it d C -P "O -H h dh p 0 3 M p s s g n3 Td 10 0) o T3 o A. d 0) p 0 Fw (1) 03 H d P 3 CO a B H oO o TJ (A d 0) ort M j > TP H A. r4 d a o a> o U to 02 q P 02 02 dd G> o o o o 'fi* 02 02 o 03 M B1 t) rl to -P <1> O O fl O H w 3 P 0) d (d O (J 0)C5 o o F^ fit) oi cd o Ft -P GJ O -P W Sh fi oo <P <P O -P oo cJ <u ^ 8 to ^ ij H fi g R.-H 00 Vi p -p O a. 0 0 rH tH P0 aa aM <D 3 s O ao P CO o O F< o o a, d M MFI o *d 0 -p 0 rH a s O O & i3n Ed co fdj fXt (3 d 0 pi H a A. i--1 to CO FJ ou d p to CO 1--1 0) d o o o ao o 3 P O o w 5S CO r- d CO KT 0017896 75 5. Summary (1) The manufacture of tetraethyl lead and the preparation of Ethyl Gasoline involve definite occupational hazards, but means of control have been such that no cases of lead poisoning have occurred in these plants for a period of years. (2) The possible hazards involved in the distribution and use of Ethyl Gasoline would be expected to be of a different order of magnitude from those which occur in the manufacturing processes, since the high dilution of tetraethyl lead with gasoline greatly modifies its toxicological characteristics. In accordance with these expectations no cases of lead poisoning are known to have occurred from exposure to Ethyl Gasoline, despite the fact that no means for the application of precautionary measures against exposure could be developed among the large numbers of unsupervised Ii I garage mechanics and filling station attendants. (3) An experimental study in 1929-30, carried out on a group of men rep resenting the severest known exposure to Ethyl Gasoline and its combustion products, shows an agreement with earlier investigations, in that no evi dence of lead absorption, as a consequence of the exposure, has been obtained, when comparisons of this group is made with corresponding groups of unex- 0017897 (4) A group of men who have been exposed to Ethyl Gasoline, continuously. over a period of years, show no increase in their lead absorption, as measured by their lead excretion, over that of the same individuals two years previously. (5) A group of workmen with an intense skin exposure to Ethyl Gasoline failed to show evidences of increased lead absorption after a period of six months of such exposure. (6) Two individuals who were under observation for four months, during which duplicate samples of their food, as well as their excreta, were analyzed, excreted a total amount of lead which was little greater than that found in their food. During a similar four months period, in which they were exposed to Ethyl Gasoline and its combustion products, no change in their rate of lead excretion was detected. 1 0017898 6. Conclusions Further examination of the possibilities of danger to the public health from the distribution and use of Ethyl Gasoline in the United States has failed to yield evidence of the existence of such dangers. The study of groups of persons whose occupations have magnified their exposure to a point \ well above that which is possible in the general population, has'given no rea son to believe that appreciable lead absorption results from the combination of lead exposures which have been hypothecated. Danger from absorbing lead through the skin through contact with Ethyl Gasoline may now be said to be non-existent. The crucial observations under conditions of human exposure agree with previous facts ascertained by animal experimentation. Lead absorption from the inhalation of finely divided lead compounds in the exhaust gas of automobiles using Ethyl Gasoline, has not been shown to be appreciable. Garage mechanics, chosen by reason of the intensity and dura tion of their exposure to such exhaust gases, showed no signs of lead absorption. The specific criterion employed for the detection of lead absorption, namely, evidence of increased lead excretion, has been found to have a high degree of sensitivity, even for short periods of exposure. Since the subjects employed in this investigation have had exposures ranging from one to six years, continuously, the absence of signs of lead absorption means that no significant lead exposure existed. With the observation that the lead which is excreted by normal human beings is derived largely from food materials, it becomes apparent that the mag nitude of this factor in lead absorption may be sufficient to mask the effects due to the use of Ethyl Gasoline. If this be time, the insignificance of the contribution made to the lead absorption of the community, by the advent of KE 0017899 jthyl Gasoline, is thereby established. Moreover, an attempt to measure the ri 1 jthyl Gasoline factor in lead absorption, while controlling the food factor, Ses resulted in failure. The conclusion is inescapable that lead absorption in the community, as the result of the distribution of Ethyl Gasoline, is insig- . I aificant. 2 1 - j 1 A 4 \ 1 ! 0017300 79 6. Bibliography 1. Kehoe, Robert A. On the toxicity of tetraethyl lead and inorganic lead salts, Jr. Lab. and Clin. Med. 12, 554, 1927* 2. Kehoe, Robert A., and Thamann, Frederick: The behavior of lead in the ani mal organism. II Tetraethyl lead; Am. Jr. Hygiene, 15, 478, 1931. Sayers, R. R., et al: Experimental studies on the effect of Ethyl Gasoline and its combustion products, U. S. Bureau of Mines Publication 4! 1927. - -r4 1 4. Leake, J. P., et al: The use of tetraethyl lead gasoline in its relation to the public health. U. S. Public Health Bulletin Ho. 163, 1926. Final Report of the Departmental Conmittee on Ethyl Petrol: Ministry of Health - London, 1930. 5 6 (a) Eehoe, Robert A., and Edgar, Graham: A study of the hazards associated with the sale and distribution of Ethyl Gasoline, printed Re I port to United States public Health Service and Ethyl Gasoline 5 Corporation, June 1925. i (b) Kehoe, Robert A. et al: Report similar to above dated Kay 1927. I (c) Kehoe, Robert A. et al: Report similar to above dated April 1928. 1 I I K 0017901 80 Appendix 1 The Present Status of the Hazards of the Manufacture of Tetraethyl Lead and Ethyl Fluid The dangers associated with the manufacture of tetraethyl lead hare teen controlled through the joint application of engineering and medical know ledge. It has teen possible to design essentially closed systems for the pro duction, distillation, purification and storage of tetraethyl lead; to handle sludge, to reclaim the residual lead after the completion of the reaction; to mix the tetraethyl lead with the other ingredients of tetraethyl lead; and to fill suitable containers in preparation for shipment by rail or water. With sound toxicological information available it has proven to be feasible to use ventilating equipment in such a way as to maintain a safe atmosphere in work rooms, despite the occurrence of localized air contamination with lead com pounds, incident to daily operation of the plant. Constant supervision of ' plant activities is maintained for the sake of safety as well as productivity. An exact technique for every operation is prescribed, with due regard to safety. In addition to these measures, every person who is employed in any part of the plant area is under medical supervision. Each workman is seen by a physician every week, and in case of absence from work by reason of any kind of illness, investigation of the character of the illness is made promptly. Blood examinations, including an erythrocyte count, haemoglobin determination and the examination of a film for stippling of erythrocytes, are carried out every third week. Measurement of the lead concentration in the air of various parts of the plant are made in such a way that the entire plant is thus in vestigated quarterly. As a further check on the plant conditions the lead excretion of representative groups of workmen is determined at quarterly in tervals. During a period of six years in vhich such a regime has been in J ' KP 0017902 81 effect, there have been no cases of lead poisoning among the workmen. More over, no workman has been removed from his employment by reason of symptoms of impending lead intoxication. In a few instances, men without symptoms have shown an increase in basophilic stippling or some other sign which may have teen due to absorption of lead, whereupon they have been transferred to posi tions which involved little or no lead exposure, either temporarily or permanent ly. The labor turnover has been very small, however, so that most of the workpen have been employed at the same type of work for four to six years. The jphyaical character of the plant is such that men engaged in specific parts of the operation are sharply segregated from each other. Excepting the general supervisors, who spend variable periods of time in all parts of the plant, {and also the staff of men who carry out maintenance and repair of equipment, |the workmen can be grouped in accordance with their specific occupations, j The above circumstances have provided an opportunity for prolonged study of the lead excretion (and stippling of the erythrocytes) of groups of |workmen who are representative of the cross-sectional lead hazards of the f < {plant. The conditions as to lead exposure have not remained constant during I the period of such observations. As potential hazards have been recognized <they have been eliminated or reduced. To this extent the combination of all the results for the past five years does not give an exact picture of present I jconditions. On the other hand, the number of subjects used at one time was l {Necessarily small, so that repeated observations over the entire period re peal the situation most satisfactorily. Several representatives of each type i of work were selected as characteristic subjects. Observations on the same subjects have been repeated quarterly so that the number of items recorded in the data represent the total number of observations. It is not necessary for present purposes to describe the operation 0017903 of the plant In detail. The general nature of the procedure is indicated in the following classification of the workmens (1) Handlers of a lead-sodium alloy, made hy heating lead and sodium in a melting pot; (The alloy is made, poured, cooled, ground to suitable size, and weighed into hoppers, by these workmen.) (2) Autoclave operators, who introduce the alloy into the autoclave without coming into contact with it, and who tend the autoclaves during the re action whereby tetraethyl lead is produced; (3) Still operators, who regulate the distillation of tetraethyl lead from the reaction mixture and residue; (4) Furnace operators, who reclaim unused lead from the sludge by a melting process; (5) Blenders, who take-the finished product, tetraethyl lead, and mix it with other ingredients, to prepare a fluid which ultimately is to be in troduced into gasoline; (6) Laboratory workers, whose analyses of alloy, 3ludge and finished product provide information for control of the manufacturing operations; and (7) Foremen, who supervise the various operations. The exposure is of two types, essentially, - that occasioned by lead dusts, and that arising from the escape of tetraethyl lead vapors. The re spiratory channel alone is of practical importance, in the absorption of lead, under the present plant conditions. The furnace operators and the alloy workers have little or no exposure to tetraethyl lead, vapors. On the other hand the still operators, the blenders and the laboratory workers are not ex posed to dusts. The hazards of autoclave operators are chiefly from vapor, but the possibility of dust inhalation cannot be entirely ignored. The fore men move about from place to place but they spend their entire time in the plant. They are subject to all the possibilities of exposure in the entire KE" 0017904 jlant, to a considerable degree. The other groups are limited to the exposure characteristic of their own occupation and area. In accordance with the above facts a series of tables has been con structed in which the groups of workers with related exposures are handled to gether, so far as possible. Tables 40 A, 41 A, and 42 A present the analyti cal findings for the still operators, autoclave operators, blenders and labora tory workers, while Tables 40^B, 41_ B and 42 B give the findings for the furnace operators, the alloy workers, the foremen, and for the entire group in crosssection. The results shown in these tables are clearly different from those which have been obtained on workmen in dusty lead trades. Indeed, the lead exposure of the laboratory group falls within normal limits, as judged by lead excretion. The number of observations, in the case of this group is too small to produce any appreciable effect upon the composite group, so that the mean values for the latter may be taken as properly representative of conditions of exposure in the plant. One other matter of importance is suggested in the relationship be tween the mean urinary excretion and the mean faecal content, for certain groups. If we employ the concept that faecal lead content is a measure of ex posure to lead compounds, it would appear that the exposure of the furnace operators is approximately equivalent to that of the still operators. Yet the urinary excretion of the former group is significantly small as compared to that of the latter. This may be due to the large variability inherent in a limited number of observations, but it seems more probable that it is an ex pression of the difference in the physiological activity of different lead com pounds. Tetraethyl lead vapor is readily absorbed, whereas particulate metallic lead and lead oxide are doubtless absorbed more slowly from the lung surfaces. This may explain why the stillmen, exposed only to tetraethyl lead 0017905 TABLE 40 A Distribution of Workers in the Manufacture of Tetraethyl Lead According to Lead in a Single Sample of Faeces j. 85 Lead in Milligrams per Sample of Faeces 0 -0.09 0.10-0.19 0.20-0,29 ! 0.30-0.59 0.U0-0.L9 0.50-0.59 0.60-0.69 0.70-C.79 0.80-0.89 0.90-0.99 1.00-1.09 1.10-1.19 1.20Totals Still Operators Autoclave Operators 2 3h h h. 52 3k 73 30 22 11 21 1 11 6* 1* 37 26 Blenders 2 2 b 3 .5 1 1 2 18 Laboratory Workers 3 7 1 1 12 i | ^ Mean | Probable 1 Error of Mean J Standard Deviation 0.51 ^0.03 -0.25 Excluded in Calculation of Means ^Calculated on Y/ider Distribution 0.l to.olt -O.Jl 0.39 to.cb *0.26 0.15# 0.02 0.08 i 0017906 2 TABLE 41 A Distribution of Workers in the Manufactoring of Tetraethyl Lead According to Milligrams of Lead Per Gram Ash of Faeces 86 Jigrams of leac Still Operators Autoclave Operators Blenders >r Gran of Ash Number Percentage Number Percentage Humber Percentage Laboratory Workers Number Percentage 0 -0.04 0.05-0.09 C. 10-0.14 0.15-0.19 -1 0.2C-0.24 i 0,25-0.29 i 0.50-0.24 0.55-0.59 j !o.40-0.44 i *0.45-0.49 ; 0.50-0.54 | {0.55-0.59 1 1,0.60-0.64 1 10.65-0.69 1 lO.7C-0.74 IP.75-0.79 | lO. 80-0. 84 lo. 85-0. 83 lo.9C-0.94 Llotals 8 10 7 8 2 i i 27 2 11.5 21.6 5 19.2 . 5 27.8 5 41.7 27.1 8 20.7 5 27.8 6 50.0 18.9 5 11.5 4 22.2 1 8.3 21.6 1 2.9 5.4 5 11.5 1 5.5 2 11.1 2.7 2.7 i i 2.9 3.9 1 5.5 i * 5.9 100.0 26 100.0 18 100.0 12 100.0 lean 0.171 0.165 Probable Error If Mean i o.oio 0.018 Standard levl&tion i 0.090 0.154 I * Excluded in Calculation of Mean Calculated on wider Distribution i KE" 0017907 0.181 0.021 + 0.155 0.112 0.007 0.027 vapor from day to day show a higher rate of lead excretion in the urine than do the furnace operators. This explanation gains in plausibility when it is ob served that all the groups exposed chiefly to tetraethyl lead vapors (excluding the essentially unexposed laboratory workers) have a higher rate of urinary exsretion, in proportion to their faecal output, than do the groups exposed to lead dusts. In the matter of stippling of the erythrocytes, as shown in Tables 43 A and 45 B, we fail to find a differentiation of the workers in this plant. From this alone, it is perfectly clear that though stippling may be a valuable Indication of the occurrence of lead absorption, the number of stippled cells :annot be employed as a criterion in making fine distinctions as to the magni tude of lead exposure and lead absorption. 1 fi 4 KX 0017908 TABLE 42 A Distribution of Workers in the Manufacture of Tetraethyl Lead According to Milligrams of Lead Per Liter of Urine 87 lligrans of Lead r Liter of Urine Still Operators Autoclave Operators 0-0.03 04-0.07 08-0.11 12-0.15 16-0.19 20-0.23 24^0 27 28-0.51 Oj~Q c5 56-0.39 40-0.45 44-0.47 48-0.51 52-0.55 56-0.59 10-0. S3 54-0.67 tals 1 5 2 8 4 5 4 3 1 1 2 56 2 6 4 4 4 2 1 1 1 25 Blenders 2 4 5 1 5 2 17 Laboratory Workers 5 6 1 12 k jbable Error .Kean ^dard Ration 0.198 "to. 014 "to.120 0.146 tO.105 to. 108 0.151 to.010 *0.060 0.05 0.006 0.031 Hi 0017909 TABLE 40 B Distribution of Workers in the Manufacture of Tetraethyl Lead According to Lead in a Single Sample of Faeces 88 Lead in Milligrams per Sample of Faeces o -0.09 0.10-0.19 0.20-0.29 0.30-0.39 0lj.0-0.i;9 0.50-0.59 ' 0.60-0.69 0.70-0.79 0.80-0.89 0.90-0.99 1.00-1.09 1.10-1.19 1.20Totals Furnace Operator b 3 1 3 1 1 2 2 1 h* 18 Alloy Y/orkers 3 2 h 3 1 2 1 3 li* 23 Foremen Combined Groups 2 12 7 28 7 25 8 25 3 15 2 15 37 28 7 5 3 .. 5.............. 2* 17* 36 170 Mean Probable Error of L "ean i Standard t Deviation 0.56 to.06 0.36 0.38 0.02; to.26 0.3b to. 02 to. 19 O.i-i-18 to. Oil; *0.261 Excluded in Calculation of Mean These consist of 13 widely scattered results from 1.20 to 2.50, and i; results from 3.00 to 5.00. Including all results except the last four, the mean far the combined groups is 0.50ij. mg. to.023, a Standard Deviation of 0.J+U6. KF 0017910 - > fnar'^r'T' nr TABLE 41 B Distribution of Workers in the Manufacture of Tetraethyl Lead According to Milligrams of Lead Per Gram Ash of Faeces 89 ILlligraas of jead per Gram jf Ash Furnace Operators Mo. % Alloy Workers No. ' % Foremen No. % Confined Groups No. ' % C-0.C4 3.05 -0.03 3.10-0.14 3.15-0.19 3.20-0.24 ' 3.25-0. 3 D.30-C.34 3.15-0. 59 3.4C-0.44 0.45-0.49 3.50-0.54 0.55-0.53 0.50-0.64 0.65--0.69 0.70-0.74 0.75-0.79 0.36-0. 8-1 0.95-3. 33 .0.90-0.94 .Totals 3 16.7 4 22.2 3 16.7 1 5.5 2 11.1 1 5.5 2 * 11.1 O # 18 11.1 100.0 4 17.4 1 2.8 8 3 13.0 9 25.C 38 7 30.4 11 30.6 51 1 4.4 9 25.0 28 3 13.0 2 5.5 15 2 5.5 10 2 8.7 1 2.8 5 2 1 4.4 1 4.7 22.3 30.0 16.5 8.8 5.9 2.9 1.2 0.6 4O^ 8.7 4 '` 1 3 2.3 0.6 1.8 23 100.0 1 0.6 1 # 2.8 1 0.6 2 1.2 36 100.0 170 100.0 iiean 0.201 ! t>,hg 0.186 Probable Error J>f Mean 0.017 0.007 to.009 Standard Deviatio 10.158 *0.065 0.136 * Excluded in calculation of Mean Excluding the last twelve aberrant results the mean is 0.147* 0.004, with a Standard Deviation of 0.078. K 0017911 TABLE 42 B Distribution of Workers in the Manufacture of Tetraethyl Lead According to Milligrams of Lead per Liter of Urine 90 Milligrams of Lead per Liter of Urine Furnace Operators Alloy YiO rkers 0-0.03 0.04-0.07 0.08-0.11 0.12-0.15 0.16-0.19 0.20-0/23 0.24-0.27 0.23-0.31 0.32-0.35 0.3S-0.39 0.40-0.43 0.44-0.47 0.48-0.51 0.52-0.55 0.56-0.59 0.60-0.63 JO.64-0.67 .Totals 4 4 5 i 2 1 1 1* 17 4 10 7 1 1 1* 24 Foremen 9 9 7 3 4 1 1 34 Combined Gooups 21 42 28 25 15 12 8 2 4 2 1 3 1* 1* 165 Jean 0.140 0.074 Probable Error .of Mean 0.012 -0.005 Standard deviation 0.073 0.038 Excluded in calculation of means. 0.092 0.008 0.070 0.129 0.005 0.098 0017912 TABLE 43 A Distribution of Workers in the Manufacture of Tetraethyl Lead According to Stippling of Erythrocytes 91 Nunber of Stippled Cells per 50 Field 0 1-4 5-8 9-12 15-16 17-20 21-50 31-40 41-60 61-80 85 94 97 146 Totals Still Operators Autoclave Operators 67 10 7 33 32 21 61 51 51 11 1 37 25 BlendeiTS 3 3 4 1 1 1 2 1 1 17 Laboratory Workers 3 3 2 1 1 1 1 12 t Mean Probable Error _of Means Standard ^Deviation 12.64 "tl.3^ "til. 88 10.21 1.87 13.62 Means calculated on even distribution. 13.38 2.27 15.85 11.59 2.37 11.64 K 0017913 lumber of tippled Cells ier 50 Fields TABLE 43 B 92 Distribution of Workers in the Manufacture of Tetraethyl Lead According to Stippling of Erythrocytes Furnace 0Taerators Alloy Workers _____________L Foremen Confcined Grouos 0 1-4 5-8 9-12 13-13 17-20 21-30 31-40 41-60 61-80 85 94 97 146 Totals 2 8 -1 2 5 i i 18 5 12 5 1 2 1 24 10 10 5 3 3 1* 1* 1* 1* 1* 36 36 53 16 11 10 9 12 10 5 3 1* 1* 1* 1* 1 169 Ban 10.83 8.54 rob able Error i Mean *2.34 1.81 tandard fiviation 14.72 13.15 * Excluded in Calculation of Means Means Calculated on even distribution. 8.95 1.39 11.51 10.77 0.68 12.95 Kt 00179!4 Lead in Milligrams per Sample of Faeces 0 -0.09 0.10-0.19 0.20-0.29 0.30-0.39 O.I4.O-O.J4.9 0.50-0.59 0.60-0.69 0.70-0.79 0.80-0.89 0.90Totals TABLE 44 Distribution of Workmen Employed in Miring Tetraethyl Lead with Gasoline According to Lead in a Single Sample of Faeces 93 1927 r~ ........- ........ .. | 1929 1931 l----------------- Composite -, Number 16 7 5 3 2 1 % Ui-.1l 19.1+ 13.9 8.3 5.6 2.8 Number 3 11 9 6 1+ h 2 % 7.5 27.5 22.5 15.0 10.0 10.0 5.o Number 7 10 9 5 1+ 1+ 3 1 % 15.2 21.7 19.6 10.9 8.7 8.7 6.5 2.2 Number 26 28 23 11+ 10 9 5 1 % 21.3 23.0 18.8 11.5 8.2 7.1+ 1+.1 0.8 2* 5.6 1* 2.5 36 100.0 l+o 100.0 3* 6.5 6* 1+.9 1+6 100.0 122 100.0 Mean Probable Error of Mean Standard Deviation 0.20 -0,02 0.19 0.29 to. 02 to. 16 Excluded in Calculation of Means 0.29 to. 02 to. 19 0.261| to.on to.176 0017915 TABLE 45 Distribution of Workmen Employed in Mixing Tetraethyl Lead with Gasoline According to Milligrams of Lead per Gram Ash of Faeces 94 illigram of eaa per Gram f Ash 0-0.02 .03-0.05 .06-0.03 .09-0.11 .12-0.14 .15-0.17 .13-0.20 .21-0.23 .24-0.26 .27-0.29 .30otals 1927 No. % 14 38.9 10 27.8 4 11.1 4 11.1 1 2.8 1 2.8 2* 36 5.5 100.0 192 9 No. % 3 7.5 12 30.0 10 25.0 8 20.0 1 2.5 2 5.0 1 2.5 1 2.5 2 5.0 40 100.0 1931 No. % 5 10.8 13 28.3 14 30.4 9 19.6 4 8.7 Compos ite No. % 22 18.1 35 28.7 28 23.0 21 17.2 5 4.1 1 0.8 2 1.6 2 1.6 1 0.8 1* 46 2.2 100.0 5* 122 4.1 100.0 san 0.051 0.084 rcbable Error f Mean 0.004 0.006 tandard aviation 0.035 0.056 * Excluded in Calculation of Means 0.070 0.004 0.038 0.070 0.003 0.047 KE 0017916 TABLE 46 Distribution of Uorkmen Employed in Mixing Tetraethyl Lead, with Gasoline According to Milligrams of Lead per Liter of Urine 95 Milligrams of Lead per Liter of Urine 0-0.01 0.02-0.05 0.04-0.05 0.06--0.C7 0.08-0.09 0.10-0.11 0.12-0.15 C.14-0.15 DJ3 -0.17 0.18-0.19 0.20 Totals 1927 1929 195 L Cornslosite Number Percentage Number Percentage Number Percentage Number Percentage 2 5.6 2 5.0 19 41.5 25 18.9 4 11.1 10 25.0 14 50.4 28 25.0 11 50.5 8 20.0 6 15.0 25 20.5 9 25.0 8 20.C 2 4.5 19 15.6 4 11.1 6 15.0 1 2.2- 11 9.0 5 8.5 2 5.0 5 4.1 2 5.6 2 5.C 4 5.5 1 2.5 1 2.2 2 1.6 1 2.5 1 2.2 2 1.6 1 2.8 1 0.8 2 * 4.5 2 * 1.6 56 100.0 40 100.0 46 100.0 122 100.0 iSean 0.068 Probable Error of Mean *0.004 .Standard Deviation 0.036 0.066 0.004 0.037 0.033 0.005 0.034 * Two results 0.52 and 0.64 excluded in Calculation of Means 0.C55 0.002 0.039 0017917 TABLE 47 Distribution of Workmen Employed in Mixing Tetraethyl Lead with Gasoline, According to Stippling of Erythrocytes - *tA - ; 96; 4; A* '.`A'V. N'umber of Stippled Cells cer 50 Fields 1927 19 29 19 51 Compc>site. 1 ' 1 i P'ilSfiftl T'-m 0 25 67.6 17 43.5 16 34.8 58 -- 47.51 1-4 10 27.0 8 20.5 13 28.2 31 5-8 9-12 15-16 17-20 21-24 25-49 50-74 Totals 2 37 5.4 1 2*6 7 15.2 4 10.2 5 10.9 10 _ :-T> 41 9 A 7*41 3 7.7 V 1 2.6 1 2.2 1 2.6 ; 1 2.2 ! 2.6 3 6.5 5 7.7 3 Jlj 2 ' 1.6;l I 'i,?! 2 --v j U! 4 3 a 100.0 39 1C0.0 46 100.0 122 100.0 ! '-I Approximate I.'ean 1.66 5.06 Probable Error of Mean -0.22 -0.67 Standard Deviation -2.02 ^5.88 Calculated on a wider distribution 4.40 0.54 5.22 3.79 + 0.31 : 4.85 ^ p & k- $ KE 0017918 97 co a KB 0017919 OJ K\ in vO The results of the foregoing observations coincide with the chemical evidences that the manufacture of tetraethyl lead has been carried out in such a manner as to prevent extensive lead absorption among the plant operators. On the other hand, certain groups of the workmen can be differentiated from per sons who are not exposed to lead, despite the fact that the magnitude of their lead exposure has not been sufficient to produce symptoms of lead intoxication. Thi3 fact demonstrates the sensitivity of measurements of lead excretion as a means of estimating lead exposure. The extent of this sensitivity in the general method is displayed graphically in Table 48 in Appendix 2, where a classification of groups of subjects of variable lead exposure is made in terms of the magnitude of their mean lead excretions. Appendix 2 The Present Status of the Hazards in the Manufacture of Ethyl Gasoline by Mixing Ethyl Fluid with Gasoline Since 1925 Ethyl Gasoline has been prepared at gasoline refineries and large bulk distributing centers by means of special equipment, designed and prescribed by the Ethyl Gasoline Corporation. Regulations for the operation of the equipment, and for the safeguarding of the mixing personnel have been pro mulgated, and medical supervision of the operating personnel has been maintained by the medical staff of the same corporation. There are approximately two hundred points at which the mixing is carried out, and from one to six men are employed at each point to carry out all the operations concerned with the handling of the materials and their containers. The opportunities for lead ex posure in the course of normal operation are meagre and since mixing is not required more frequently than once a week, such exposure is irregular in KE 0017920 occurrence. Nevertheless, the potential hazards of the work are sufficient to justify the maintenance of precise technique and adherence to the prescribed precautionary measures. No cases of lead poisoning have occurred among these workmen, and no person has been removed from his employment as a result of occupational lead ab sorption. In coincidence with this indication of the safety of the work, ob servations of the lead excretion, and of stippling of the erythrocytes of repre sentative groups of workmen fail to give evidence of a significant lead absorp tion. Tables 44-47 show the findings obtained from time to time in the study of such workmen. It is not possible to differentiate them from persons in the normal unexposed population. The last table (Table 48) gives the mean results obtained in our study of several groups of persons within the lead trades and outside the lead trades. This table has been referred to previously, as evidence of the sensitivity of the method of estimating lead exposure and lead absorption, through the accurate determination of the lead output in the faeces and in the urine of representa tive groups of exposed persons. K 0017921 APPENDIX III APPROXIMATE GROSS AND COMPARATIVE SALES OF ETHYL GASOLINE IN 1950 AND 1931 1950 Millions of Gals. of Ethyl Gasoline (0.S.) Percentage of Ethyl Gasoline to Total Gasoline 1,854 11.7 1951 Millions of Gals, of Ethyl Gasoline IH.SQ Percentage of Ethyl Gasoline to Total Gasoline 1,970 12.0 AVERAGE CONCENTRATION OF TETRAETHYL LEAD IN ETHYL GASOLINE IN 1950 AND 1951 1950 1.84 cc/gallon 1951 1.91 cc/gallon KE 0017922