Document jB7ean26jjx2ZB131vJeZKkQ9

SiZZZN 2 r;cioo -t--- . t ht- TABLE OF CONTENTS PREFACE PAGE (1) THE NATURE OF THE LEAD H A Z A R D S ... ...... ........ ................... 5 Hazards Associated with Manufacture of Tetraethyl Lead and Ethyl G a s o l i n e ...................................... Possible Hazards Associated with the Use and Distribution . of Ethyl G a s o l i n e ........................... ........... The Distribution and Sale of Ethyl G a s o l i n e ....... ...... . 5 7 11 (2) PREVIOUS INVESTIGATIONS OF ETHYL GASOLINE IN RELATION TO PUBLIC HEALTH ....................................................... 16 (3) INVESTIGATIONS CARRIED OUT IN 1929-50 .................... .......... 16 The Selection of Experimental Subjects ......................... Methods of S t u d y ........................ ............. ........... Experimental F i n d i n g s ...... ................. .................. Comparison of the Findings of 1929-50 with Results Obtained E a r l i e r .................................... 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 G a s o l i n e ................ 67 (5) S U M M A R Y ............................................................. 75 (6) CONCLUSIONS ......................................................... 77 APPENDIX (I)......................................................... The Present Status of the Hazards of the Manufacture of Tetraethyl Lead and Ethyl F l u i d .................. 80 APPENDIX (II)................... ..................................... The Present Status of the Hazards in the Manufacture of Ethyl Gasoline by Mixing Ethyl Fluid with G a s o l i n e .... 98 APPENDIX (III)............................... .-............ .......... The Sale and Distribution of Ethyl Gasoline in the United States to 1952 ............ ........ ........... . 100 /' TITLES OF TABLES Number (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. (A) History Sheet. (B) Physical Examination Sheet. . (C) Neurological Examination. (D) 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 Groups of Subjects Not Exposed to Ethyl Gas oline, Examined in 1927. .# 5'": : 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. I (24) Distribution According to Lead Found in Faeces of Groups of Subjects Not Exposed to Ethyl Gasoline, Examined in 1927. U 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. 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 (5asoline 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 vshich 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. 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. 6 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 Pb} 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 strange 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 hygienic 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 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 Qazollne. 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 I other points of difference which have not required the test of experience for a' f: their recognition. Ethyl Gasoline contains tetraethyl lead in amounts so small I that the solution has lost the essential toxicological properties of tetraethyl a lead. Thus, whereas tetraethyl lead alone, or in high concentration in gasoline, y is absorbed through the skin rapidly, its absorption is`retarded greatly by % dilution in gasoline. Indeed we have been unable to obtain avidence of appre- I The results which have been obtained through attention to details in the use S of special equipment, and through the inauguration and operation of suitable y safety measures are described in Appendices 1 and 2 of this report. 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 A n 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. 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 tank 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 sapors may occur. Of much more importance, however, is the appearance of a new set of conditions baaed upon the combustion of the fuel.' Tetraethyl lead is converted, thereby, into finely divided inorganic lead compounds (chiefly lead bromide}, which are deposited, in part, along the exhaust system, but which, 0therwi3e, are discharged into the atmosphere with the exhaust, gases of the J s 10 motor. The extent of the accumulation of exhaust gases from many automobiles in busy oity 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 shin 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 shin, they may be a further means of 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 oi 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 piched up by currents and mixed into the air breathed by workmen. 11 Cine 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 by 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 'olume of distribution during thib time except for a period of almost a year bQginning in May, 1925. At this time Ethyl Gasoline was withdrawn from the ^^ket pending an investigation of the United States Public Health Service, bbough for various reasons its use was not interrupted in certain areas in which n e - 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 d e a r indication of the areas in which the greatest opportunities for lead -wpoaure have been provided. They also yield a graphic conception of the pro^rtions of the problem which confronts us. TABLE 1 .Period, of Distribution, of Ethyl Gasoline in Various American Cities Up to October 1929 13 locality Dayton, Onio Cincinnati, Ohio Wheeling, '. Va. Chicago, 111. Detroit, Mich. St. Louis, Mo. Kansas City, Mo. Minneapolis, Minn. Milwauiiee, Sis. Baltimore, ill. Washington, D.C. San Antonio, Texas Savannah, Ga. Atlanta, Ga. Jacksonville, Fla. Lew Orleans, La. Cleveland, Ohio Philadelphia, Pa. Boston, Mass. ___ Denver, Colo. w -Baa Francisco, Cal. ___ Angeles, Cal. ___ Spokane, 7?ash. ^Jftilsa, Okla. fork City Date of First Distribution February 1923 April 1923 Summer 1923 Autumn 1923 Autumn 1923 Spring 1924 Spring 1924 Spring 1924 Spring 1924 Spring 1924 Spring 1924 Spring 1924 Autumn Autumn Autumn Summer Siammer Summer Summer Summer Suaaner Summer 1924 1924 1924 1926 1926 1926 1926 1926 1927 1927 Summer 1927 Summer 1927 Autumn 1928 Interval of Discontinuance none none May 1925 to summer 1926 May 1925 to Summer 1926 May 1925 to Summer 1926 May 1925 to Summer 1926 May 1925 to Summer 1926 May 1925 to Summer 1926 May 1925 to Summer 1926 May 1925 to Summer 1926 May 1925 to Stammer 1926 May 1925 to Summer 1926 none 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 IO . to ti / fivi in o 0017335 > - i ;, -.1.-, > u M\ t n t> w i TABUi Z Approximate Gross and Comparative Consumption of Ethyl Gasoline in Various Areas of the United , From 1926 to Octobor of 1929 Jp - Distribution Areas of the ; United States O o. NgW England States and ^ New York Pennsylvania ; Atlantic ; Coast States Ohio ; Kentucky, Georgia Florida ' Mississippi Alabama Louisiana . Arkansas Tennessee Central States Texas, Oklahoma Rocky Mt. States West Coast States TOTAL 19 26 Millions of Percentage Gallons of Ethyl Gaso line. of Ethyl Gasoline to Total Gasoline. 8.0 0.5 5.0 0.9 7.0 0.7 1.0 0.15 3.0 0.36 0.5 25.0 0.8 2.5 0.0 52.8 0.2 0.8 0.1 0.8 0.0 0.58 1927 Millions of Gallons of Ethyl Gaso Percentage of Ethyl Gasoline line. to Total Gasoline. 1928 Millions of Percentage Gallons of Ethyl Gaso line. of Ethyl Gasoline to Total Gasoline. M G E l 52.0 3.2 91.0 4.9 30.0 4.4 75.0 9.9 6.0 0.6 18.0 1.4 16.0 2.1 93.0 10.8 18.0 1.9 39.0 3.7 0.5 110.0 4.0 10.0 30.0 276.5 0.2 8.0 2.9 3.3 172.0 4.9 0.5 8.0 0.8 3.1 16.0 4.3 2.1 27.0 1.8 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 Tetrs.ethyl 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 1.4* 1.1 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 be somewhat in error. KT 0017337 2. Prevlou'3 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. On. 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 Service^ studied the matter in 1925, and the Ministry of Health of Great Britain3 criti cally reviewed the previous experimental work and made further contributions to it in 1928. Bach 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 reports 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 e*perimental work carried out by ourselves or others, except to point out that i0ne of them disclosed evidence of danger either to the health of persons en- HE 0017838 gaged in the handling of Ethyl Gasoline or to that of the general public. In the ligit 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 b y 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 handl- Ethyl Gasoline for the longest period of time, who had handled gasoline con-, lining the highest concentrations of tetraethyl lead, and who handled the ^^Sest amounts of Ethyl Gasoline daily, were especially desirable. Until May 6i 1925 a small metering device containing a liter can of Ethyl Fluid was used 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 aubjects 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 *bo had been working on cars which used only Ethyl Gasoline, and an additional ainety-three who had been repairing cars of which a high percentage used such S&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 ~thyl Gasoline exclusively over a period of several years. Ten members of the H Z 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 tdiich 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 hy 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 transportetj. on. The barrels were filled in a specially constructed room pro vided with forced ventilation. Despite the magnitude of ventilation the con juration of gasoline vapor was high enough to be immediately disturbing to 6&e who was not accustomed.to 3uch vapors. In addition, the skin, clothing k'r 0-017341 7ABLE 4 Distribution of Subjects According to Occupation and Locality 20 t 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 Maas 'Wheeling W* Va* : Bew fork i -- ^___New fork \ ^TOTAL 56 Number of lank 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 48 5 5 5 5 5 50 10 27 201 27 Number of Barrel fillers Exposed to Ethyl Gasoline #251 - #272 22 22 K f 0017342 21 and shoes of the workmen were frequently and almost continuously soaked with gasoline. The barrels were lined up in a double row along corresponding rows 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 valve refused to work properly, at which time a stream of gasoline rose from the drum and thoroughly drenched any workmen in its inmediate vicinity. The number of men engaged in filling and handling the drums of gaso line was small but the severity of exposure was such as to give excellent oppor tunity for the detection of any effects which might result from gasoline absorp tion. These men were carefully examined in a manner which will be described later, and several types of laboratory data were obtained, including the lead content of the urine and faeces. (These latter data were obtained because of our interest in the lead excretion of groups of workmen with no occupational exposure to lead compounds.) Shortly after these examinations had been completed the refinery in Question undertook the distribution of Ethyl Gasoline. The latter was handled the manner described above for ordinary gasoline. Inasmuch as experimental 87i&ence indicated that the hazards of lead absorption from skin contact and .inhalation of vapor from gasoline containing tetraethyl lead were practically Eligible, no fears were entertained as to the consequences of the additional f&ctor of a low concentration of tetraethyl lead. Nevertheless, this constituted * Unique situation from the point of view of severity of exposure. Therefore considered imperative to obtain infornation 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 tfE" 0017343 22. 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 Tdiich 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 fector of leaded gasoline. Fortunately, such ata were adequate. Furthermore, repeated observations had been made on the same individuals under conditions of continuous exposure. These successive Endings furnish a means for the discovery of progressive effects of any type. ^ Ikoda of study. Experimental studies on animals and men have established the exist- i*ac of a relationship between the magnitude of lead exposure and absorption ^ the rate of lead excretion, in that faecal excretion is a measure of inges- 5 on the day preceding the collection of the sample, while the urinary ex^etion indicates the magnitude of lead absorption. Data which substantiate s 80 points are presented later in this report under heading "4. investigations : aued since 1930." nevertheless, considering the importance of the matter K E 0017344 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 S -r 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 s 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 auong 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 Judgment 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 Importance, in determining whether or not any evidence of lead intoxication ksi 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 *51 by opposing the examiner's strength to that of the corresponding muscle ..*P of the subject. But for the purposes of statistical comparison of a |.|lQls neuro-nuscular factor, the grip was tested by a hand dynamometer. (The ^ Instrument was employed throughout the tests.) Measurements of the blood pressure of each subject while seated, were with a standard manometric apparatus. R E 0017345 24 A. HISTORY SHEET HO. Examiner*s Initials pate Name Age Hace Color Birthplace Marital Ages Children .Miscarriages Stage Hesidenee 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 Founding Soldering Enameling Paint Mfg. Pottery Glass Polishing Cut Glass White Lead Rubber Garage Telephone or Telegraph Rep. Automobile Owner 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: K H 0017346 A. HISTORY SHEET (Cont) No. Examiner's Initials Hate Sleep Hours in Bed Hreams Restful Disturbed Bowel Movements Frequency Hour Tendency to Constipation Cathartics Tendency to Frequent Stools Teeth Brushing When Last Trip to Hentist 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 Different Meals Digestive Disturbances Hausea or vomiting Skin Infection or Eruption General Hands Polyuria Nocturia Frequency nervousness General Wealmess * Other Complaints Right or Left Handed Loss of Strength in Arms or Legs at any time ^ Shooting pains .Numbness or tingling .Loss of Sensation KT 0017347  ' mm 26 B. PHYSICAL EXAMINATION SHEET" No. Examiner's Init. Bate Age Height General Appearance Nutrition pulse Temperature Color of S M n (exact) Po sture Musculature Blood Pressure (seated) Condition of Skin Condition of Skin of Hands Cornea Sclera Nose Throat Glands Tonsils Mucous Membranes Ears (structure) Teeth Gums Pyorrhoea, lead tine (Appearance and Location) Heart Apex Hate After 25 hops 2 minutes after 3.C.D. R.S.D. x Itngs; Z.I. - R. L. D.E. H. L. Xi*Xj*B* -- B. L. Weight ^3t diagnosis Spleen Genitalia Extrem ities l**SU0.3i3 and Remarks Kidneys Lower Extremities KH' 001734 C. KEOROIOGICAL EXAMIHATI CM Examiner's init. Cranial serves I Smell II Sight R - 15/ L - 15/ Condition Correction III, IV, VI Extrinsic Eye Muscles Pupils Reflexes Visual Field V Motor Sensory ,rII VIII Audition R L Facies Equilibrium IX, X, XII Speech Swallowing Tongue XI ITeck Shoulders ^Pper Extremities Tonus Atrophy Ataxia Tremor Muscular Power Dynamometer . Stereognostic ; Spicritic Protopathic f Kinaesthetic ? Thermal i 1Tihratory XervQ Trunk Tenderness "v'or Extremities Reflexes Pharyngeal Biceps Triceps Radial Petellar Achilles Epigastric Abdominal Cremasteric Plantar Gait 27 K F - 0017349 D. LABORATORY SHEET no. Examiner's Initials Date URDIALYSIS: Quantity Sp.G. Reaction {Methyl Red) Altunin {Heller's) Heat and Acetic Sugar {Fehling*s) Acetone (Hitroprusside) Microscopic BLOOD: White Count Haemoglobin (Dare) Eed Count Differential {100 cells}: Poly. neutrophiles Poly. Eosinophiles Poly. Basophiles Lymphocytes Endothelial Large Mononuclear Transitional Stippling per 50 fields Abnormal Polychroraasia ^ALFTIGAL SXMJIHATICST: Accurate statement of hours required for collection of: Urine Faeces 1; Constipation Diarrhoea Cathartic (type) 1 FAECES 77't * d ish d rie d f a e c e s di3h ash dish dried faeces ash lead Mgs. Mgs./gram of ash A n a ly s is Ho. * Volume URIHE c.c. Lead Mgs. Mgs./ l i t e r Analysis Ho. KE 0017350 28 29 A fresh specimen of urine was obtained from each subject and examined at once for its 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 .emoglobinoneter. A single instrument was employed for all observations, . readings were made by the same observer. Blood smears were made on all subjects, and were examined for stippling erythrocytes by the method previously described. Samples of urine and faeces were obtained from the subjects for the .nation of their lead content. The collection of these and the analyses .rried out according to methods which we have described in an earlier re in a few instances no samples were obtainable. A further snail number >les were lost in transit and in process of analysis. With these few .ons, the analytical results were obtained without difficulty. lental Findings. Ho case of lead intoxication was found among the subjects. In fact, dnation of symptoms and physical findings was suggestive of lead intoxiSuch evidences of lead absorption as are common among lead workers were uously absent. Of special negative clinical importance were the complete i of lead line, the lack of si^xifleant microscopic blood changes ing), and the striking infrequency of vague symptoms of ill health. :hese circumstances any evidences of significant lead absorption as a Kr 0017351 30 consequence of exposure to Ethyl Gasoline must be 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 bad repaired cars which used Ethyl Gasoline over a period of three years or more. 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 lets had been employed in trades which involved some opportunity for lead ab sorption, prior to their exposure to Ethyl Gasoline. Hone of the .garage mebanica 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*9a9(i that few garage mechanics have more than a slight lead exposure in the ?Qnrse 0f their normal day's work, since small jobs of soldering and painting, the occasional repair of a storage battery have not produced a noticeable * 'srrence of lead intoxication among garage mechanics. Cue tank wagon driver ight garage mechanics had been employed at some previous time in hazardous tJQA j wades, in which their exposure had not been severe either in quality or The distribution of the subjects according to age, seen in Table 7, - K E 0017352 "S'- i IABLB 6 31. Distribution of Subjects According to Period of Exposure to Ethyl Sasoline _ Period of Exposure in Years 0.1-0.25 0.5 1 2 13 4 15 I6 TQ2AL3 Pilling Station Attendants Number % 12 6 11 16 28 25 41 10 18 66 100 lanJc Wagon Handlers Number i 12 48 48 19 38 16 32 6 12 50 100 Garage Mechanics Number a 26 13 36 ' 18 98 49 22 11 12 6 73 201 100 Barrel Piliers Exposed to Ethyl Gasoline Number % 4. 18 16 82 22 100 I 1I 0017353  3P SABLE 6 32 distribution of Subjects According to History of Previous Exposure to Lead Other Than Ethyl Gasoline - Description Pilling Station Tank Wagon Garage Barrel Fillers of Attendants Handlers Mechanics Not Exposed to Lead Exposure ' Ethyl Gasoline Number % Number .* Number % Number % None 20 36 18 36 15 55 t4 Questionable 8 14 10 20 30 15 6 30 1|' Slight 28 50 21 42 163 82 3 11 0, Moderate 12 84 1 4 P TOTAL 56 100 50 100 201 100 27 100 Barrel Fillers Exposed to Ethyl Gasoline Number % 10 46 6 27 6 27 22 100 K P 0017354 TABLE 7 Distribution of Subjects According to Ago 33. Age in '/ears 15-19 20-24 25-29 20-34 35-39 40-44 45-49 50-54 1 55-59 t f 60-4 1 65-69 *5 1 _ otal Filling Station Attendants Tank Wagon Handlers Oarage Mechanics Number % 35 12 21 12 21 59 24 59 47 7 13 6 11 56 100 Number 15 7 10 5 5 3 1 3 1 50 56 30 14 20 10 IO 6 2 6 2 100 Number 9 32 : 33 34 42 26 11 8 4 2 201 * 4 16 17 17 21 13 5 4 2 1 100 Barrel Fillers Not Exposed to Ethyl Gasoline Number * Barrel Fillers Exposed to Ethyl Gasoline 1 i| Number 56 6 23 5 19 5 19 6 23 14 14 28 15 29 6 27 29 7 31 29 15 15 26 100 22 100 1 K' R Probable R tror of R B Standard ^ ^wiation 40.6 .2 13.07 36. 6 il. 1 11. 28 34 .3 0 .5 9 .86 37.9 1.2 8.76 39. 1 1.3 9. 34 K 0017355 TABLE 8 Distribution of Subjects According to Certain Subjective Abnormalities 34, Type of Abnormality Hecent Loss of Weight 56 Filling Station Attendants Humber % 36 50 Tank Wagon handlers 201 Oarage Mechanics Number O/f Number % 2 4 74 27 Barrel Fillers Not Exposed to Ethyl Gasoline Number <?/ Increased Tendency to Fatigue 1 2 1 2 84 2 7 Frequent . Headache 6 10 2 4 31 15 2 7 Occasional Abdominal Cramp 2 4 2 4 12 6 1 4 Occasional 1 Digestive 3 Disturbance 3 5 2 4 42 1 4 9 Occasional Kauri tic 3 Symptoms 3 5 73 M ?oor S General S^JIealth 11 22 Barrel Fillers Exposed to Ethyl Gasoline Number * 15 15 15 15 K.Z 0017856 4t 35. 3 TABLE 9 Distribution o f Subjects According to Certain Objective Abnormalities Type of Abnormality Under Nutrition Filling Station Tank Wagon Attendants Handlers Garage Mechanics Number % Number of f Number Jo 4 6 248 4 Pallor 2 4 2 4 23 11 Irritation of Skin of Hands 11 20 12 24 56 28 lead line Kerve Trunk Tenderness 6 11 17 34 17 8 [ Tremors 20 36 21 42 71 35 [ Sensory | DisturbanI 063 1 2 364 2 I Extensor I Paresis 1 2 361 1 K Atrophy of I Upper KxI treaities 1 2 4 89 4 Abnormalities of Visual JJf t el d 2 4 12 Urinary J^sidity 20 39 15 33 92 46 ^mai nuria 496 3 Barrel Fillers Not Exposed to Ethyl Gasoline Barrel Fillers Exposed to Ethyl Gasoline Number % 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 H B 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 most 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 thair exposure to gasoline. Comparison of the enaining items with the results of similar observations on various groups of Ejects unexpo3ed to Ethyl Gasoline fails to yield any significant informaion. (Of. Tables 19 and 20). In Tables 10, 11, and 12, the findings as regards blood pressure, ^arnoglobin of the blood, and stippling of the erythrocytes are recorded, uo values were computed for the occurrence of stippling by reason of the high ,rPortion of negative results. It may be seen from the tables that no sigiificance may be attached to variation in these matters in relation to Ethyl *5Une exposure, since practically all the findings are within normal limits. *" Wie case of the systolic blood pressure, which is used here only as a ^ 6tal means of pointing out the probable existence of vascular disease, the M headings are sharply correlated with age, and hence have no significance. K 0017358 The 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 i?orn contamination of the sample or from the ingestion of unusual amounts of tcad with food material, and that they have no necessary or probable relation,!iP to occupational lead exposure. Accordingly the inclusion of such findings the computation of mean values increases appreciably the probable error of Reans. TTevertheless, such results have been recorded, and have been in*uded in the calculations unless otherwise specifically noted in the tables. -ere a result has been excluded it has been for the obvious purpose of sli tting a finding which has no possible relation to the problem at issue. the case of the urine samples, aberrant results are of rare occurrence, as he expected. On the other hand, contamination of an occasional sample the process of collection is apparently unavoidable, despite the most K 0017359 TABLE 10 Distribution of Subjects According to Systolic Blood Pres s u r e 38. Blood Pressure Headings Filling Station Attendants Tank; Wagon Handlers Garage ~ ~- Barrel Fillers Barrel Fillers Mechanics Humber % Humber % Humber A Humber % Humber * 30-59 30-39 12 100-109 35 110-119 10 18 120-129 16 32 130-139 * 140-149 9 16 7 12 150-159 24 ' : 160-169 J 170-179 12 ,- ^1 180-169 24 i Jo Information 3 5 -j jotal - . 56 100 11 42 2 4 16 8 16 32 52 26 10 20 62 30 7 14 36 18 4 8 18 9 24 52 3 64 2 4 7 8 5 1 2 24 21 4 611 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 -'V s ; :Probable Error 2ean >5r*<M;S ^tcdard '*J^Jliation 130.1 1.7 17.86 130.4 1.9 19.30 125.7 0.7 15.10 134.3 1.8 13.59 129.1 2.3 15.86 H E 0017300 iw- #I' IABLB II Distribution of Subjects According to Haemoglobin in Blood 39 Baemoglobinometer Beading (Dare) 60 - 67 66 - 75 I 75 - S3 1 84 - 91 1 92 - 99 jSo Information Billing Station Attendants lumber A % 15 27 21 57 15 27 59 Tank Wagon Handlers Humber 1 % 2 48 12 24 27 54 5 10 12 Oarage Mechanics Humber % 13 6 77 39 92 46 15 7 42 Barrel Fillers Not Exposed to Ethyl Gasoline Number 9 2 33 12 44 4 15 14 14 Barrel Fillers Exposed to Ethyl Gasoline Number % 15 15 8 35 11 50 15 Jiotal 56 100 50 100 201 100 27 100 22 100 [loan. ri jProbable error i{ fflean ^ Standard Inflation 80.9* 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 6.54 K X 0017861 TABLE 12 40. Distribution of Subjects According to Stippling of Erythrocytes I Number of Stippled 1 Cells Per I 50 fields I0 11 I 2-5 1 -10 1 11 ~Z0 21 -32 J Total Filling Station Attendants Number 35 6 5 3 3 2 56 O/f 64 11 11 5 5 4 100 Tarde Wagon Handlers Garage Mechanics Number 33 8 5 2 1 1 % Number % 66 159 79 16 19 9 10 17 8 453 211 2 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 n IE 1 Wz Z9S1I00 - o o n s o> S' TABLE 13 41 Distribution of Subjects According to Strength of Grip of left Hand '-----------Hand Dynamometer Heading ; 50-59 Filling Station Attendants Number CP7 50-69 12 70-79 7 12 ' S0-S9 i \ 90-93 59 7 12 : 100-109 I 110-119 10 18 24 J 120-129 12 1 150-139 H H O -149 12 M 150-159 J 160-169 M So m *a^or&tioa Jjotal 22 56 39 100 Tank; Wagon Handlers Garage Hachan!ce Number 2 % Numb er 44 24 5 24 8 3 6 30 13 26 47 6 12 42 2 4 20 7 14 25 5 24 5 121 2 O/ A 2 1 4 15 23 21 10 12 3 3 1 1 Barrel Fillers Not Exposed to Ethyl Gasoline Number % 5 19 27 4 15 3 11 6 22 27 14 10 20 9 4 4 15 50 100 201 100 27 100 Barrel Fillers Exposed to Ethyl Gasoline Number % 29 3 14 29 7 32 3 14 4 18 14 22 100 .irobable ^ror of *{*ndard Ration 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 K E 0017863 TABLE 14 Distribution of Subjects According to Strength of Grip of Right Hand 42 Hand Dynamometer Filling Station Attendants Heading Number cl 50-59 60-69 70-79 80-69 35 90-99 8 14 100-109 48 110-119 7 12 120-129 59 130-139 35 140-149 24 150-159 12 160-169 No Information 23 41 Total 56 100 Tank Wagon Handlers Garage Mechanics Numb er $ 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 1 211 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 % 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 K ` 0017864 TABLE 15 Distribution of Subjects According to Lead Found in P&eces 43 Milligrams of Lead Far Sample of raeces -0.079 Filling Station At tendsmts .Number 6 % 11 [ 0.OS-0.159 5 9 1 0.10-0.239 12 21 I 0.24-0.319 4 7 I 0.32-0.399 8 14 I 0.40-0.479 2 4 1 0.48-0.559 2 4 1 0.56-0.639 1 2 0.64-0.719 0.72-0.799 0.60-0.879 1 2 0.65-0.959 0.96-1.039 0.04-1.119 1.12-1.199 lefiQ-- -h 2* 4 So .^Information ` piotai 13 56 22 100 Tank; Wagon Handlers dumber 1 $ 2 48 48 6 12 6 12 24 5 10 24 12 12 Garage Mechanics Barrel Fillers not Exposed to Ethyl Gasoline Humber % Humber 53 2 56 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 63 1* 2 6* 3 3* 17 34 13 6 50 100 201 100 27 11 100 Barrel Fillers Exposed to Ethyl Gasoline . Humber % 29 9 40 5 22 15 29 15 15 1 5 22 100 i j 0.258 0.360 1 Stable 2rror of +0.018 +0.023 3t&ndard #viation 0.169 0.197 Emitted in calculation of means. 0.379 +0.012 " 0.245 0.380 +0.037 0.266 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 Filling Station Attendants Number 10 % 18 0.04-0.079 14 24 0.0S-0.119 9 16 0.02-0.159 4 8 0.16-0.199 2 4 0.20-0.239 1 2 0.24-0.279 1 2 0.28-0.319 - 0.32-0.359 1 2 0.36-0.399 --1 0.40-0.439 0.44-0.479 0.46-0.519 0.56-0.599 ' ^ `64-0.679 Mi.oo- + Ip M formati on 1* 13 56 2 22 100 Sank Vagn Handlers Number 2 % 4 16 32 48 36 36 12 12 12 12 1* 2 17 34 50 100 Garage Mechanics Number 5 != 2 51 25 54 27 36 16 18 9 84 42 42 11 Barrel Fillers Not Exposed to Ethyl Gasoline Barrel Fillers ExpoBed to Ethyl Gasoline Number % Number % 14 9 33 7 32 7 26 8 36 3 11 , 2 9 2 7 3 14 1 4 29 14 14 52 2 7 31 1* 1 13 6 201 100 27 100 22 100 |K*Ha o.oe7 0.120 0.123** 0.131 0.137 0.113 K ' ot --- --- ^K^^stion iO.007 0.065 in Calculation of Mean. dO.014 0.115 do.004** 0.005 0.074** O.lOO 0.014 0.106 0.007 0.052 Calculated after exclusion of three results over 0.64 milligrams. K E 0017366 SABLE 17 Distribution of Subjects According to Milligrams of Lead Per Liter of Urine 45 Milligrams of Lead Per Liter of Urine billing Station Attendants Humber % 0-0.039 C. 04-0.079 18 15 32 27 : 0*08-0.119 13 23 0.12-0.159 3 5 0.15-0.199 3 5 j 0.20-0.239 1 2 ] 0*24--0.279 O.2o-0.ol9 ----- - 0.32-0.359 i ----------- 0.30-0.399 :_ * 0.40-0.439 :3 0.44-0.479 --- ] 0.46-0.519 0.52- + 1** 2 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 1231 123 1 1211 11 11 11 1211 1** 2 3* 1 Barrel Fillers Not Exposed to Ethyl Gasoline Number % 6 22 16 60 5 18 Barrel Fillers Exposed to Gasoline Number b 8 36 10 45 29 15 M^foraaticn 2 4 10 20 8 4 15 ^Vtal 56 100 50 100 201 100 27 100 22 100 -m 0.071 0.089 0.066 M Abatis j | ^ror of i S l^^idard JmT*&tion 0.005 0.050 0.011 0.099 0.004 0.079 9411 calculated on a wider grouping of findings. Qluded in calculation of means. 0.058* 0.009 0.071 0.052* 0.004 0.030 H E 0017367 46 *careful instruction, of the subjects. This is not remarkable when the ubiquity I of lead compounds is appreciated, and when the lack of under standing of chemical cleanliness on the part of the subjects is taken into account. The analytical results serve to classify the various groups of subjects as distinctly outside the hazardous lead trades. At first glance,, the mean values 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 osa their significance. Finally, for reasons which will appear later, it is -j lapossible 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 `his standard, the groups fall into the category of persons lacking occupationli exposure to lead compounds. A special significance derives from the failure of the barrel fillers * abow 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 the 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 ex- *U!'e to Ethyl Gasoline, no one person shows an increase in his rate of lead tetion. This can be interpreted only as meaning that there was no sigH. * 0aut lead absorption as a consequence of this exposure. Thus, it seems K Z 0017868 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 is 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 persons who had 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 froup ia made up of only a small number of men carefully selected in 1926 as hacking any exposure to Ethyl Gasoline. The rigid requirements in the latter ?egard introduced considerable difficulty into the problem of obtaining co operative subjects. Ifo explanatory comments are required, since the tables present the Served facts adequately^, It should be pointed out that the observations horded, in these tables were made by the same persons who collected the data $5 ft ne exposed subjects previously described. The clinical methods employed in g _ 0017363 1 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 mnexposed 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 fceces also shows certain statistically significant variations within the groups, but no actual importance can be attributed to these differences in Tlev? of the variability in the size of the faecal samples. When the la.tter kctor is corrected by expressing the lead in the faeces in relation to the Entity of ash, the variability of the groups becomes statistically insig!ificant. Influence of Previous Occupational Lead Exposure, It has been intimated previously that some significance may be at- pshed to the fact that a considerable number of the subjects had been exposed ^ ead compounds in previous occupations. Likewise the handling of lead coma<*3 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 ^Ge mechanic. As a means of ascertaining the importance of these matters, K Z 0 0 1 ' . " , : 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. HE 0017371 TABLB 18 Distribution According to Age of Groups of Subjects Not Exposed To Ethyl Gasoline, Examined in 1927 50. I Age la 1 Years 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 _ 70-74 '* _ Total & i V.. s Mean Probable Error of Mean Standard t- __Deviation Medical Students Number 11 51 9 . * 15 72 13 71 100 22.3 0.2 2.3 Pilling Station Attendants and Tarde Wagon Handlers Number 1 % 1 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 37.5 0.8 12.54 31.2 0.8 6.69 I ABLE 19 Distribution According to Certain Subjective Abnormalities of Groupa of Subjects Not Exposed to Ethyl G a s o l i n e - Scamined in 1927. 51. 1 lype 1 of I Abnormality [ Recent loss I of Weight 1 Increased I leniency to fatigue Occasional Headache i Occasional Abdominal Cramp Occasional Digestive Disturbance Occasional Neuritio Symptoms Poor General _ Health 71 Diedical Students Number % 7 10 9 13 15 21 11 11 23 69 Filling Station Attendants Number % 1 1 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 K 0017373 IA B I S 20 Distribution According to Certain Objective Abnormalities of Groups o f S u b j e c t s N o t E x p o s e d to E t h y l G a s o l i n e - E x am i n e d i n 1 9 2 7 52 lype of abnorm ality U n iernutrition P a llo r irritatio n of S h i n o f Ec>nu s lead line ! tremors ' Sensory ; Disturbances l Urinary | Ability | ----------s ^Albuminuria 71 'liedical Students Number or p 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 d* P 23 9 13 4 10 9 13 25 3 4 16 38 3 4 37 4 11 39 13 8 23 39 ? s 0017374 TA3 LS 21 Distribution According to Systolic Blood Pressure of Groups of Subjects Not Exposed to Ethyl Gasoline, Examined in 1927 53. Blood Pressure - Headings ' 100-109 j 110-119 : ; 120-129 : 130-139 140-149 150-159 160-169 j 170-179 j130-189 190-199 200-209 10-219 .-5 ! 220-229 1 230-239 Total Medical Scudents Number 1 22 23 17 7 1 G/'' 1 31 33 24 10 1 Pilling Station Attendants and Tant Wagon Handlers Number 22 15 13 32 28 29 25 15 13 97 22 11 11 33 33 11 71 100 1 114 1 100 Garage Mechanics Number 6 14 7 5 3 % 17 40 20 14 9 35 100 Mean Probable Error of Mean standard ,,J^7iation 125.9 0.8 10.20 138.2 1.5 23.45 129.8 1.3 10.98 TABLE 22 54 Distri b u t i o n According to H a e m o g l o b i n of Blood of Groups of Subjects Hot Exposed to Ethyl Gasoline, Examined in 1927 Haemoglooinometer Beading IDare) 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 TanA 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 TABLE 23 D i s t r i b u t i o n According to Stipp l i n g o f Erythrocytes o f Groups o f Subjects Not Exposed to Ethyl Gasoline, Examined in 1927. 55 Number of Stippled Cells Per 50 Fields . Medical Students 0 1 2-5 6-10 11-20 21-32 Total 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 Load Found in Faeces of Groups of Subjects Hot Exposed to Ethyl Gasoline. Examined in 1927 56. I S Milligrams of Lead :|9 Per Sample of 'a Faeces 1 0 - 0.079 ^9 C.OS * O 159 1 0.16 - 0.239 1 0.24 - 0.319 9 0.32 - 0.399 9 0.40 - 0.*79 m 0.48 - 0.559 0.56 - 0.639 a 04 -- 0*719 1 0.72 - 0.799 1 O.SO - 0.679 1 0.8b - 0.959 1 0.96 - 1.039 I 1.04 - 1.119 1 1.12 - 1.199 I 1.20 1 _ Total Medical Students Humber 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 8 8 11 6 4 14 3* 11 26 100 _ Mean 0.232 Probable Error of Mean -0.019 Standard __ Deviation -0.0236 Excluded in calculation of means. 0.197 -0.013. -0.159 0.235 -0.029 -0.205 0017878 TAJBLE 25 D i s t r i b u t i o n A c c o r d i n g to M i l l i g r a m s o f lead. P e r G r a m Asia o f F a e c e s of Groups of Subjects Not Exposed to Bthyl Gasoline, Examined in 1927 57 Milligrams of Lead Per Gram of Ash 0 - 0.049 0.05 - 0.099 : 0.10 - 0.149 0.15 - 0.199 0.20 - 0.249 0.25 - 0.299 0.30 - 0.349 = 0.35 - 0.399 i1 0.40 - 0.449 i 0.55 - 0.599 i 0.65 - 0.699 3 -- 1.50-4 ____ Total :3 -" 't Medical Students Number 29 16 9 3 1 % 48 27 15 5^ 2- Filling Station Attendants Number 29 26 8 4 % 41 31 11 6 11 11 1 2- 1 1 2- 1 60 100 2* 71 2 100 Garage Mechanics Number 12 6 1 2 1 1 1 % 46 23 48 4 44- 28 26 100 Mean J Probable Error of *3 ^ Mean Standard Deviation 0.079* to. 008 0.094 0.077** 0.006 0.071 *Mean Calculated on a wider grouping of Findings. " Excluded in Calculation of Mean. Calculated after exclusion of two results over 0.65 milligrams. a 0.085 0.131 0.012 0.023 0.085 0.177 K 0017873 TABLE 26 D i s t r i b u t i o n A c c o r d i n g to M i l l i g r a m s o f Lead P a r Liter of U r i n e o f G r oups o f 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 X: -- 069 0.27 - 0.299 0.45 - 0.479 0.54 - 0.569 0.66 - 0.689 1.00 - +To tal Medical Students Humber 11 22 16 10 1 1 1 1 % 17 34 25 15 1-+ 1+ 1+ 1+ 1 1+ 1* 1 + 65 100 Pilling Station Attendants Humber 11 20 17 6 4 3 5 % 15 28 24 6 6 4 7 1 1+ 1* 1 + 1* 1 + 3 4 72 100 Garage Mechani os Number 8 4 5 2 5 % 31 4 15 .''iv 1 9 .5 8 19 14 1* 4 eg 26 100 f|| Mean Probable Error of Mean 0.078 0.007 Standard Deviation 0.089 Excluded in calculation of means. 0.081 0.006 0.069 0.077 0.008 0.059 K E" 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 J \ determined largely by the rate of lead ingestion. Previous observations have shown that under conditions which permit the inhalation of finely divided lead J i compounds, in the dusty lead trades, the quantity of lead in faecal samples is J 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. Cn 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 informt ion as to lead -1 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 *ith 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 M d e n c e which has established these facts, nevertheless, one series of ob ligations which illustrate the facts may be described on account of its direct Nation to the main problem of this report. K6 , 0017882 Description of Subjects Age in Years i Medical Students Not Exposed to Ethyl Gasoline Examined In 1927 22.3 *0.2 Filling Station and Tank 7/agon Handlers Not Exposed to Ethyl Gasoline-Examined in 1927 Filling Station Attendants Exposed to Ethyl Gasoline Examined in 1929 Tank Wagon Handlers Exposed to Ethyl Gasoline, Examined m 1929. Garage Mechanics Not Exposed to Bthyl Gasoline Examined in 1927 Garage Mechanics Exposed to Ethyl Gasoline, Bxamined in 1929 Barrel Fillers Not Exposed to Ethyl Gasoline Barrel Fillers 37.5 *0.8 40.8 *1.2 38.6 *1.1 31.12 *0 8 34.3 *0.5 37.9 *1.2 Systolic Blood Pressure (Sitting) 125.9 *0.8 133.2 *1.5 130.1 1.7 130.4 *1.9 129.8 1J.u*X 125.7 *0.7 134.3 *1.8 Haemoglobin Readings 89.8 *0.6 Lead in Mgs. In Single Sample of Faeces Lead in Mgs. Per Gram Ash In Faeces 0.232 0.019 0.079 0.008 Lead Per of Ur 0. *0. 86.0 0.5 0.197 0.013 0.077 0.006 0. *0. 80.9 0.67 85.0 *0.59 88.0 *0.7 84.5 *0.24 71.1 *0.92 0.258 0.018 0.360 *0.023 0.235 0.029 0.379 *0.012 0.380 *0.037 0.087 0.007 0.120 *0.014 0.131 *0.023 0.131 *0.005 0.137 0.014 0. 0. 0. *0. 0. 0. 0. 0. 0. *0. TABLE 28 Mean Values of Lead in Faeces and Urine of Filling Station Atten dants and Tank Wagon Handlers, Exposed to Ethyl Gasoline, Exclud ing All Besults Obtained on Persons With OtHer Industrial Exposure to Lead Compounds. 61. Lead in Milligrams In Single Sample of Faeces Lead in Milligrams Per Gram Ash in Faeces Lead in Milligrams Per Liter of Urine dumber of Subjects Filling Station Attendants Esqposed to Ethyl Gasoline 0.338 0.043 0.069 0.009 0.063 i 0.009 19 Tank Wagon Handlers Exposed to Ethyl Gasoline 0.277 0.035 0.116 0.024 0.063 0.010 15 Combined Filling Station Attendants and Tank Wagon Handlers 0.336 0.030 0.086 0.011 0.065 0.007 34 0017883 T A B L E 29 Showing Lack of Correlation Between Duration of Employment of g| Garage Mechanics and. Lead Excretion, and Duration of Exposure to Ethyl Gasoline and Lead Excretion. 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 Load in Faeces in Milligrams per Gram of Ash Length of Exposure to Ethyl Gasoline as Garage Mechanic Tilth 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 53. H TABLE 30 | 3 Distribution of Identical Subjects For the Years 1927 and 1929 |h According to Milligrams of Lead Found in Faeces. . 9 iiilligrams of Lead 9 psr Sample of Faeces wT ST 9 W m M H Jl 1 1 1 I f ,, 0 - -079 C.C8 - 0.159 0.16 - 0.239 0.24 - 0.319 0.32 - 0.399 0.40 - 0.479 0.48 - 0.559 0.56 - 0.639 0.64 - 0.719 0.72 - 0.799 0.30 - 0.379 0.88 - 0.959 0.96 - 1.039 1.83 5.10 Total Filling .Station Attendants Exposed to Ethyl Gasoline 1927 Number % 15 1929 Number 3 % 15 6 30 3 15 2 10. 8 40 3 15 z 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 1 1927 Humber * Number 2 Ill $ I! 12 J 3 17 + 2 12 I 4 23 + 3 17 + g 3 17 + 3 i7 + 2 2 12 1 6 1 3 17 + 3 17+ I 1 6I 2 12 1 !1 6 f 1 j 1 1 I1** 6 I I 17 100 17 100 1 ' ^ Mean 0.280 0.236 0.308 Probable Error of Mean 0.030 Standard Deviation 0.187 Excluded, in ca.lculatlon of mean. 0.023 . 0.155 0.025 Q..15Q______ With exclusion of single high result, the mean becomes 0.365 0.028 I 0.402** 1 0.036 11 0.218___ _i 1 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 : i l l i grams o f Lead 'e r Gran o f Ash 0 - 0.039 >.04 - 0.079 Filling Station Attendants Exposed. to Ethyl Gasoline 1927 Dumber 2 afi 10 1929 Dumber 1 5 5 25 7 35 Tank Wagon Handlers Exposed to Ethyl Gasoline 1927 1929 Number % Number % 16 7 41 4 23+ 2 12 0.03 - 0.119 5 25 6 30 5 30 3 17 - 0.159 >.16 - 0.199 0.20 - 0.239 15 15 3 15 15 15 4 23 + 2 12 3 17 16 16 9.24 0.279 -1 0.23 - 0.319 15 1 5 0.32 - 0.359 0.36 - 0.399 0.40 - 0.439 15 0.44 - 0.479 0.57 0.64 1* 5 1** 6 1.36 Total 1* 5 20 100 20 .100 _TL 1QQ_ _1Z_ 1... 00- 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 TABLE 32 65. Distribution of Identical Subjects for the Years 1927 and 1929 According to Milligrams of Lead Per Liter of Urine 4 --- i l Mil ligrams of Lead 3 Per Liter of Urine *i I j M % H 1 \ *- 0 - 0.039 0.04 - 0.079 0.03 - 0.119 0.12 - 0.159 0.16 - 0.199 0.20 - 0.239 0.24 - 0.279 0.28 - 0.319 0.32 - 0.359 0.36 - 0.399 0.40 - 0.439 0.58 0.37 1.00 4.00 - + Total Pilling Station Attendants Exposed to Ethyl Gasoline 1927 Number 1929 df Number 3 li 7 % 27- 9 35 7 27- 6 23 9 35 3 11 0 0 14 1 4 28 1 4 14 14 1 26 100 26 4 100 Tank Wagon Handlers Exposed to Ethyl Gasoline 1927 Number 10 42 1929 Number 6 11 1 %t 25 1 46 , I 5 21 3 11 + 2 1 8+ 1 4+ 1 1 4+ 1 4+ 1 .1 4+- : I 1 4+ 1 4+ 1 4+ 1 B 1 4h 2* 8 + 24 100 24 100 Kean Probable Error of ^ Kean 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 TABLE 33 Summary of Kean Values of Lead Pound In Sanples 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 0.280 0.236 Single Sample of Faeces 0.030 0.023 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 9 Lead in Milligrams Per 3 Gram Asb in Faeces 0.118 0.1C6 0.015 0.009 0.109 0.008 0.142 0.019 0.114 0.008 0.124 0.011 9 lead in Milligrams per 9 Liter of Urine 0.142 0.111 0.024 0.025 0.129 0.015 0.115 0.024 0.136 0.015 0.113 0.017 Lumber of Subjects 26 26 24 24 50 50 i i I t - K 0017888 rmwtrffnfr^iltI lead Exposure in the Handling of Ethyl Gasoline Early in 1931 we made use 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 he 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 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. Por four months these subjects were kept under observation at the laboratory. During this period a duplicate sample of every article of food 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 he analyzed. Each subject also collected twentyfour hour samples of his faeces and forty-eight hour and seventy-two hour 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 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 3ale of Ethyl Gasoline constituted not less than thirty-five per cent of the total gasoline business. Every effort was made to see that a KE 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 with 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 with 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. T A B L E 5I4. D i s t r i b u t i o n of t h e D a i l y Food. S a m p l e s o f T w o N o r m a l S u b j e c t s , During a Control Period of Observation, According to Lead Content 69 v-i ' if*rjSjilligrsms of Lead 1; -0.01+ 13,05-0.0 9 - V?' ~S'~ `i-.i 3,10-0.li+ lj.15-0 .19 .if-<f$^| 0.20-0 .21+ 80.25-0 .29 ' . 0.30-0 .31+ io.35-o.3 9 110,1+0 -OJ+I+ 0.1+5-O.1+9 .1 0.50 -0 .51+ -> 0.55-0 .5 9 j 0.60-0.61+ 1 0.6 5-0 .6 9 0.70 -0 .71+ s Jotal .- j . k1 Subject H 17 29 23 Hi12 6 1 2 1 U 1 1 111 Subject M 13 23 21 17 17 7 5 2 2 2 2 111 Both Subjeots - - ................................. 52 I4U 31 29 13 6 h ....... 3 . 2 6 _ 1 1 222 Mean Probable Error of 1 Mean 1 *j Standard ^Deviation 0 .1 5 5 0 .0 0 8 t o . 132 0 .1 6 8 0 .0 0 7 0 .1 1 3 0 .1 6 1 "0 .0 0 6 0 .1 2 3 7&SS66&-> TABLE 35 Distribution of Daily Faeoal Samples of Two Normal Subjeots During a Control Period of Observation, Acoording to Lead Content 70. 'il Milligrams of Lead W o -0 .0 7 "U o .o s - 0 .1 5 0 .1 6 -0 .2 3 3 1 0.21-0.31 i s 0.32-0.39 "W o.ho-o.h7 H 0..U 8-0.55 '1 0 .5 6 -0 .6 3 1 0.6U -0.71 1 O.7 2 -O. 7 9 1 0.80-0.87 1 0.33-0.95 1 0.96- %_ 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 15 2 2 2 1 2 250 3 * 3i. Moan Probable Error of _ Mean . Standard _ Deviation 0.239 io .013 0 . 2 2 1 0 .2 2 0 to. 0 12 0.191; 0 .0 0 8 0.197 OJ 1 01 ill* :Sf TABLE 36 Distribution of Forty-eight-hour and Seventy-two-hour Samples of Urine of Two normal Subjects, During a Control Period of Observa tion to Ethyl Gasoline, A c c o r d i n g to Lead Content. 71 Milligr eons of Lead O.Ol 0.02 0 .0 3 0.QI+ 0 .0 5 0 .0 6 0 .0 7 0 .0 8 0 .09 0.10 0.11 0.12 0 .1 3 0.11; 0 .1 5 0 .16 0 .1 7 0.18 Totals Subject H 1+3 Hours 72 Hours 11 36 18 Subject M I4.8 Hour a _____ 72 Hours 36 18 .'ean Probable Error of Mean Standard Deviation Average for 22+ Hours 0 .0 5 3 0 .0 71 *0 . 0 0 5 *0.0*42+ 0 .0 2 5 *0 . 0 0 9 -0 .0 5 5 0 .062+ 0 .0 9 7 3 ) . o q 2+ to. 0 3 2 O.O3 2 *0.008 * 0 .0 5 1 i "i'dSf TABLE 37 Distribution of the Daily Faeoal Samples of One Normal Subject During a Period of Exposure to Ethyl Gasoline, According to Lead Content Milligrams o f Lead 0 -0 . 0 7 0. 08- 0.15 0.1 6 -0 .2 3 O .2U -O .5 I O.52-O.39 O.liO-Ojtf (U -0.55 0 ,5 6 -0 .6 5 0.6U -0.71 0 .7 2 -0 . 7 9 0 .8 0 -0 .8 7 0 .8 8 -0 .9 5 O.9 6 -I.O5 1 .Ol4-l.il Totals Subject M 38 IL 21 12 7 h 2 u 1 1 1 122 72. Mean Probable Error of Mean Standard Deviation O.I9 O 0.011 0 .1 7 9 TABLE 38 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. a Milligrams of Lead m0 1 0 .0 1 a . 2 1 0.03 1 o.oU 1 0,05 1 0,06 1 0.0 7 1 0.08 1 0.09 1 0 .10 [ 0 . 11 0 .12 0 .13 o.iU _ Totals Subject H b 8 Hours 72 Hours b1 3 31 11 k 31 l2 12 12 83 23 11 1 1 1 3b 18 Subject M 1+8 Hour's 72 Hours 3 2 U3 5 3l 22 63 53 l 1 2 2 3 1 3b 18 Mean Probable Error of Mean Standard Deviation Average for 2U Hours 0 .0 6 1 0 .0 7 9 io.oou * 0 .0 3 9 * 0.006 * 0 .0 3 3 \ 0 .0 2 8 0 .0 5 1 & , 003 *b .029 0 .0 8 1 b.OO ^o.oUi . 0 .0 2 6 0017895 KET 0017896 Summary of Mean Amounts of Lead Found in Daily Samples of Food, Faeces and Urine of Two Subjects During a Control Period and During a Period of Exposure to Ethyl Gasoline. Subject Mean Daily Lead Content of Food Mean Daily Lead in Faeces Mean Daily Le Control Pd. Exposure Pd. Control Pd. Exposure Pd. Control Pd. H 0.155 Incomplete 0.239 Incomplete 0.025 M 0.168 Incocyplete 0.220 0.19 0.032 Both 0.161 Incomplete 0.224 0.028 * 75 5 . Summary (1 ) The m anufacture o f t e t r a e t h y l le a d and th e p re p a ra tio n o f E th y l G asoline in v o lv e d e f in ite o ccu p a tio n a l h a z a rd s, but means o f c o n tro l have been such t h a t no c a s e s o f le a d p o iso n in g have o ccu rre d in th e s e plants fo r a period of y e a rs. (2 ) The p o s s ib le h azard s in v o lv e d in th e d is tr ib u t io n and u se o f E th y l G asolin e would be exp ected to be o f a d i f f e r e n t o rd e r o f m agnitude from those which o ccu r in th e m anufacturing p ro c e s s e s , sin c e th e high d ilu tio n of te tr a e th y l lead with g a so lin e g r e a tly m odifies i t s to x ic o lo g ic a l c h a r a c t e r i s t i c s . In acco rd an ce with th e se e x p e c ta tio n s no ca s e s o f le a d p o iso n in g a r e known to have o c c u rre d from exp o su re to E th y l G a s o lin e , d e s p ite th e f a c t th a t no means f o r the a p p lic a tio n o f p re c a u tio n a ry m easures a g a in s t exp o su re co u ld be d ev elo p ed among th e l a r g e numbers o f u n su p e rv ise d garage m echanics and f i l l i n g s ta tio n a tte n d a n ts . ( 3 ) -An e x p e rim e n ta l stu d y i n 1 9 2 9 - 3 0 , c a r r i e d o u t on a group o f men re p r e s e n t in g th e s e v e r e s t known exp o su re to E t h y l G a so lin e and i t s com bustion p ro d u c ts , shows an agreem ent w ith e a r l i e r i n v e s t i g a t i o n s , in t h a t no e v i dence o f lead ab sorp tion , as a consequence o f the exposure, has been ob tain ed , when com p arison s o f t h i s group i s made w ith co rre sp o n d in g groups o f u n e x - 76. (4) A group o f men. who have been exposed to E th y l G a s o lin e , c o n tin u o u s ly , 1 over a p e rio d o f y e a r s , show no i n c r e a s e i n t h e i r le a d a b s o r p tio n , a s measured by t h e i r le a d e x c r e t i o n , o v e r t h a t o f th e same i n d i v i d u a ls two years p rev io u sly . (5) A group o f workmen w ith an in t e n s e s k in exp o su re to E th y l G a so lin e A % f a ile d to show e v id e n ce s o f in c r e a s e d le a d a b s o r p tio n a f t e r a p e rio d o f I six months o f such exp osu re. (6) Two in d i v i d u a ls who were u n d er o b s e r v a tio n f o r f o u r m onths, d u rin g which d u p li c a te sam ples o f t h e i r fo o d , a s w e ll a s t h e i r e x c r e t a , were analyzed, e x c r e te d a t o t a l amount o f le a d which was l i t t l e g r e a t e r than th at found in t h e i r food . During a s im ila r fo u r months p e rio d , in which they were exposed to E th y l G asolin e and i t s com bustion p ro d u c ts , no change in t h e i r r a t e o f le a d e x c r e tio n was d e te c te d . 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 '.,id jthyl Gasoline, is thereby established. Moreover, an attempt to measure the ^ jthyl Gasoline factor in lead absorption, while controlling the food factor, j 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;1 sificant. ...j : j i 79 6. Bibliography j. yehoe, Bobert A. On the toxicity of tetraethyl lead and -organic lead ealte, Jr. Lab. and Clin. Med. 12A 554, 1927. 2. Eehoe, Bobert A., and Thamann, Erederiok: rh. hehavior of lead in the ani mal organiem. II Tetraethyl lead; Am. Jr. Hygiene, 13,. 478, 1931. 3. Sayers, B. H . , et al= Experimental etadiee on the effect of Ethyl Oaeoline and its combustion products, U. S. Bureau of Mines Publication 1927. 4. Leake, J. ?., et al, The ne. of tetraethyl 1 * 4 gneoline in ite relation to the public health. B. S. Public Health Bulletin Ho. 163, 1936. 6. Pinal Beport of the Departmental Conrcittee on Ethyl Petrol: Ministry of Health - London, 1930. 6. (al Eehoe, Hebert A., and Edgar, Oraham: A study of the hasards associated With the sale and distribution of Ethyl Gasoline. Printed Re port to United States Public Health Service and Ethyl Gasoline Corporation, June 1925. (b) Eehoe, Bobert A. et al: Beport similar to abore dated May 1927. (c| Eehoe, Bobert A. et al: Beport similar to above dated April 1938. 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 have teen controlled through the joint application of engineering and medical know ledge. It has been 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. 17ith 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 which such a regime has been in effect, there have teen 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 ehov.n an increase in basophilic stippling or some other sign which may have been 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 work men have been employed at the same type of work for four to six years. The physical 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. 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 ;plant. The conditions as to lead exposure have not remained constant during '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 | |conditions. On the other hand, the number of subjects used at one time was i iNecessarily small, so that repeated observations over the entire period re ! weal 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 82, 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 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 vhich the groups of workers with related exposures are handled to gether, so far as possible. Tables 40 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 cross section. 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 TABLE 40 A ` Distribution of Workers in the Manufacture of Tetraethyl Lead According to Lead in a Single Sample of Faeces Lead in | Milligrams j per Sample 1 of Faeces j 0 -0.09 ! 0.10-0.19 ! 0.20-0,29 i 0.50-0.59 0.ii0-0.L9 0 .50 -0 .59 0 .60-0 .6 9 0 .70 -C.79 0.80-0,89 0.90-0.99 . 1.00-1.09 ,, 1.10-1.19 ^ 1.20. Totals Still Operators Autoclave Operators 2 3 If if if . 52 3 if 73 30 22 11 21 1 11 6 * 1* 37 26 Blenders 2 2 if 3 5 1 1 2 18 Laboratory Workers 3 7 1 1 12 I j ^ Mean Probable Error of _ Mean Standard ^ Deviation 0 .5 1 0 . 0 3 -O. 2 5 Excluded in Calculation of Means ^Calculated on Y/ider Distribution H O -H o*l;5 to.olf 0 .3 9 0 .01* -0 . 2 6 0 .1 5 # 0 .0 2 0.08 _ '1 H- 1: TABLE 41 A Distribution of Workers in the Manufactoring of Tetraethyl Lead According to Milligrams of Lead Per Gram Ash of Faeces 86 ligrams of lead Still Operators Autoclave Operators Blenders Laboratory Workers >r Gram of Ash Number Percentage Number Percentage Humber Percentage Number Percentage 0 -0.04 0.05-0.09 C.10-0.14 0.15-0.19 -1 0.20-0.24 i 0,25-0.29 i '0.50-0.54 4 0.55-0.59 j !o.40-0*44 i 0.45-0.49 'j 0.50-0.54 | 10.55-0.59 1 10.60-0.64 1 10.65-0.69 1 L0.7C-O.74 14.0.75-0. 79 Lo. 80-0. 84 Ip. 85-0. 89 |p.gc_o#94 -Ivlotals 8 10 7 8 2 i i 57 3 11.5 2 1. 6 5 19.2 . . 5 27.8 5 41.7 27.1 8 30.7 5 27.8 6 50.0 18.9 3 11.5 4 22.2 1 8.3 2 1. 6 1 3.9 5.4 5 11.5 1 5.5 2 11.1 2.7 2.7 i i 3.9 3.9 1 5.5 i * 3.9 10 0 .0 26 10 0 .0 18 10 0 .0 12 10 0 .0 Ejean 0.171 0.165 I Probable Error |^f Mean i 0 .0 10 - 0.018 1 Standard .deviation 0.090 0.134 I * Excluded in Calculation of Mean ffi Calculated on wider Distribution 0.181 0 .0 21 + 0.135 0 .112 0.007 0.0S7 . . rnpor 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 exs r e t io n , 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 13 A and 45 B, we fail to find a differentiation of the workers in this plant. From t h i 3 alone, it is perfectly clear that though stippling may be a valuable In d ic a tio n of the occurrence of lead absorption, the number of stippled cells :annot be employed a s a criterion in making fine distinctions as to the magni tude of le a d exposure and lead absorption. i i f 1 TABLE 42 A Distribution of Workers in the Manufacture of Tetraethyl Lead According to Milligrams of Lead Per Liter of Urine 87 llig r a n s o f L e a d r L i t e r o f U r in e S t ill O p e ra to rs A u t o c la v e O p e r a t o r s 0- 0.03 04- 0.07 08- 0.11 12- 0.15 16- 0.19 20- 0.23 2*1--0 .2 7 28- 0.51 52- 0.35 56- 0.39 40- 0.43 44- 0.47 48- 0.51 52- 0.55 56- 0.59 50- 0 . S 3 54- 0.67 t a ls 1 5 2 8 4 5 4 3 1 1 2 53 2 6 4 4 4 2 1 1 1 25 B le n d e r s 2 4 5 1 5 2 17 L a b o ra t o ry W o rk e rs 5 6 1 12 Sf i i jb a b le .M e a n E rro r ^ d a rd R a t io n 0.198 014" t o . " t o . 120 0.146 t o . 105 t o . 108 0.151 * 0.010 * 0.060 0.05 * 0.006 * 0.031 . TABLE 40 B Distribution of Viorkers in the Manufacture of Tetraethyl Lead According to Lead in a Single Sample of Faeces 88 Lead in ?iilligrams per Sample of Faeces Furnace Operators 0 -0 .0 9 0.10-0.19 0.20-0.29 0.30-0.39 0 j;0-0 .I;9 0.30-0.59 ' 0.60-0.69 0.70-0.79 0 .80-0 .8 9 0.90-0.99 1 .00-1.0 9 1.10 -1. 19 i 1 .20 - _ Totals 1 3 1 3 1 1 2 2 1 h* 18 Alloy Y/orkers 3 2 h 3 1 2 1 3 -U* 23 Foremen Combined Groups 2 12 7 28 7 25 8 25 3 15 2 15 37 28 7 5 3 ... ?. ..... 2* 17* 36 -H-3 O . Mean ; Probable Error of _ Mean Standard Deviation 0 .56 to. 06 0 .36 0 .38 0.02; t o . 26 0 .3U to. 02 to. 19 O.ii-18 to. Oil; to.26 l 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 500. Including all results except the last four, the mean far the combined groups is 0,50L|. mg. to.023, with a Standard Deviation of 0.J4j.6. -:*f""iaaj>narr,iaaaMii TABLE 41 B Distribution of Workers in the Manufacture of Tetraethyl Lead According to Milligrams of Lead Per Gram Ash of Faeces 89 11H i grams of jead per Gram jf Ash Furnace Operators Mo. % Alloy Workers No. ' % Foremen No. % Conjoined Groups No. % C-0.C4 105-0.03 3.10-0.14 3.15-0.13 3.10-0.24 ' D.5-0.23 D.30-C.54 3.05-0. 33 3.4C-0.44 0.45-0.43 0.50-0.54 0.55-0.53 0.50-0.64 0.65-0.63 0.70-0.74 0.75-0.73 0.30-0. 3-1 .85-0. S3 .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 2* 18 11. 1 10 0 .0 4 17.4 1 2 .8 8 5 15.0 9 25.C 38 7 50.4 11 50.6 51 1 4.4 9 25.0 28 3 15.0 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 O 8.7 4 2.3 1 0 .6 5 1. 8 25 10 0 .0 -- -- ----- 1 0 .6 1 * 2.8 1 0 .6 2 1. 2 56 10 0 .0 170 10 0 .0 i'ean 0 .20 1 ! 0,U& 0.186 Probable Error 3f Mean 0.017 0 .0 0 7 to.009 Standard Deviatio a 0.158 * 0 .0 6 5 0.186 * 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. 0017911 TABLE 42 B Distribution of Workers in the Manufacture of Tetraethyl Lead According to Milligrams of Lead per Liter of Urine 90 Killigrans of Lead per Liter of Urine Furnace Operators Alloy Yiorkers 0-0.03 0.04-O.D7 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-O.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 i).64-0.67 Totals 4 4 5 1 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 If Mean 0 . 0 12 -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 TABLE 43 A Distribution of Workers in the Manufacture of Tetraethyl Lead According to Stippling of Erythrocytes 91 Nuriber 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 Ooerators 67 10 7 33 32 21 61 51 51 11 1 37 25 Blenders 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 . 2 1 1.87 13.62 Means calculated on even distribution. 13.38 2.27 15.85 11.59 2.37 11.64 umber of tippled Cells ier 50 Fields TABLE 43 B D ist r ib u t io n o f W orkers in th e M an u factu re o f T e t r a e t h y l Lead Accordin g to St ip p lin g o f Er y th r o cy tes Furnace 0Taerators Alloy Workers ---------- 1 Foremen Conbined Gt o u d s 0 1-4 5-8 9-12 13-16 17-20 21-50 51-40 41-60 61-80 85 94 97 146 .Totals 2 8 -1 2 5 i i 18 5 10 36 12 10 53 5 16 3 11 1 10 9 2 3 12 3 10 15 1* 3 1* 1* 1* 1* 1* 1* 1* 1* 24 36 169 san 10.83 8.54 obable Error i Mean 2.34 1.81 tandard gviation 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 K 00173 !4 Lead in Milligrams per Sample of Faeces 0 -0 .0 9 0.10-0.19 0.20-0.29 0 .30 -0 .39 o.Uo-o .1+9 0.50-0.59 0 .60-0 .6 9 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 I9 27 r~ -- -- ----19 29 19 31 1----- Composite 1g Number 16 7 5 3 2 1 % JnU.lx 19.1+ 13 .9 8.3 5.6 2.8 Number 3 11 9 6 1+ h 2 % 7.5 27.5 22.5 I5 .O 10.0 10.0 5.0 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 % 2 1. 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 12 2 10 0 .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.l76 TABLE 45 D i st r i b u t i o n o f Workmen Em ployed in M ixin g T e t r a e t h y l Le ad w it h G a so lin e A cco r d in g t o M illig r a m s o f Lead p e r Gram Ash o f F a e c e s 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 .24-0.25 .27-0.29 .30otals 1927 No. % 14 10 4 4 .1 38.9 27.8 11.1 11.1 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. % Compos ite No. % 5 10.8 22 13 28.3 ^ 35 14 30.4 28 9 19.6 21 4 8.7 5 1 2 2 1 18.1 28.7 23.0 17.2 4.1 0.8 1.6 1.6 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 sviation 0.035 0.056 * Excluded in Calculation of Means 0.070 0.004 0.038 0.070 0.003 0.047 TABLE 46 Distribution of Workmen 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 C.Q6-0.C7 0.08-0.09 0.10-0.11 0.12-0.15 C.14-0.15 02E -0.17 0.18-0.19 0.20 Totals 1927 1929 193 I Comi>osite Number Percentage Number Percentage Number Percentage Number Percentage 2 5.6 2 5.0 19 41.3 23 18.9 4 11.1 10 25.0 14 30.4 28 23.0 11 50.5 8 20.0 6 13.0 25 20.5 9 25.0 8 20.C 2 4.3 19 15.6 4 11.1 6 15.0 1 2.2- 11 9.0 3 8.5 2 5.0 5 4.1 2 5.6 2 5.C 4 3.3 - 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 * 4.3 2 * 1.6 36 100.0 40 100.0 46 100.0 122 100.0 Mean 0.068 Probble Error of Mean t0.004 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 0.055 0.002 0.039 K r 0017917 TABLE 47 ;. ' ; Distribution of Workmen Employed in Mixing Tetraethyl Lead with Gasoline ``"i,-V \~y According to Stippling of Erythrocytes .Vi a'uaiber of Stippled Cells -er 50 Fields 1927 19 29 19 31 Composite, '' AV**v' 0 25 6 7 .6 1 7 43.5 16 34.8 58 47.5 1-4 10 2 7 .0 8 2 0 .5 13 28.2 31 25.4 5-8 9-12 15-16 17-20 2 5.4 1 2.6 7 15.2 4 10.2 5 10.9 3 7 .7 V 1 2.6 1 2.2 10 ''8.2 9 7.4 .ii.l'V: t- 3 .'it z . 2 21-24 . 2 5 - 4 9 ... 50-74 1 2.6 ! 2.6 1 5 j 7 .7 '1 3 2.2 6 .5 2 '"ile 4 .J V5.i 3 ,3 1 Hi8* o.. Totals 37 10 0 .0 39 j 1 C 0 .0 46 100.0 122 ' Approximate ''ean 1 .6 6 5 .0 6 Probable Error of Mean 0 .2 2 0 .6 7 Standard Deviation 2 .0 2 5 .8 8 Calculated on a wider distribution 4.40 0.54 5.22 3.79 i & +| 0.31 - b k . :i 4.85 1 % -U - ' KE 0017918 6161I00 3X TABLE 48 Summary of Mean Vaines of Lead Found in Single Samples of Faeces, of Lead in Milligra Gram of Ash in Gaeces, of Lead in Milligrams per Liter of Urine, and of Stippling of rocytes, for Various Groups within and outside the Lead Trades i Workers in White Lead Plant Workers in Electrical Storage Battery Manufacturing Plant Workers in a Tetraethyl Lead Manufacturing Plant Workers E in Mix Tetraeth in Gas 1 Lead in Milligrams in a Single Sample of Faeoes 3.76 - 0.26 2.53 1 0.18 0 .i; 2 * 0 .0 1 * 0 .2 6 2 Lead in Milligrams per Gram of Ash in Faeces 0.57 - 0.32 0J;5 * 0 . 0 3 0 . 1 9 0 .0 1 - 0 .0 7 3 Lead in Milligrams per Liter of Urine 0 .2 1; 0 . 0 1 0.18 * 0 . 0 1 0 . 1 3 0 .0 1 - 0 .0 6 h Stippled Ejxjf4u*Itiia*%vCjrw o JW-zacam 50 Fields 7j jj + t AA e7*r1r7o 4"* 1 J.a ifenVF_7f 7f t-- n.Afl jx *7i0 t_ 5 Number of Subjects or Observations 86 71 170 12 6 Significance of Lead Associated with Occurrence of Associated with Occurrence of No occurrence of Plumbism No occu of Plu 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 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 (P.S. Percentage of Ethyl Gasoline to Total Gasoline 1,854 11.7 1951 Millions of Gals, of Ethyl Gasoline B--JSO -- 1,970 Percentage of Ethyl Gasoline to Total Gasoline 12.0 AVERAGE CONCENTRATION OF TETRAETHYL LEAD IN ETHYL GASOLINE _________ IN 1950 AND 1951__________ 1950 1.84 cc/gallon 1951 1.91 cc/gallon 0017922