Document qmmVDNjXya33voYYaNq58KvZE

An Appraisal of the Lead hazards Associated with the Distribution' and Use of Gasoline Containing Tetraethyl Lead. Parti By Robert a. Kehoe, Frederick Thamann and Jacob Cholak From tne Kettering Laboratory of Applied Physiology, University of Cincinnati, Cincinnati, Ohio. Introduction and Acknowledgments. Cue development of a motor fuel containing tetraethyl lead raised certain questions in industrial and public health which have claimed an unusual amount of attention. Since IS24 members of the staff of tuis laboratory have carried on a series of studies of tne hazards associated with tne manufacture, distribution, and use of tuis type of gasoline. From time to time (1925, 1327, and IS28) reports of these studies have been made to trie Ethyl Gasoline Corporation and We United States Public Health Service, but t^e accumulated information nas not been published partly because of tne unwieldly volume of data, and partly because tne results of successive investigations were essentially similar to those described by other 'workers/ Thus our conclusions have not differed materially from those reached turougn animal experimentation by Sayers and his associates (l), or from those arrived at by Leake and other workers of the United States Public health Service (2) through the use of rnetnods generally similar to ours. Cur data (to 1928) and those of Sayers and Leake were critically reviewed by the ministry of health of Great Britain as indicated in the Final Report of the Departmental Committee on Etnyl Petrol (3), issued in 1930. Recently, it nas become evident that more definite con clusions are justified with regard to the lead exposure derived from hie use of leaded gasoline. Accordingly, in tne following pages we 2 observations, made in 1929, which continue our earlier investigations. In a second article we snail present the results of a later and more precise method of measuring the lead exposure specifically due to lead in gasoline in tne various occuppations which are concerned. V.e wish here to acknowledge an indebtedness to our associates for assistance in various items of the work; to V.'. F. Machle, L. W. Sanders, L. J. Senradin and E. Brown for their help in making the physical examinations; to L. W.. Sanders for the study of blood films;, and to I. J. LeElanc for the statistical analysis of the data. The expense of this work was borne by tne Ethyl Gasoline Corporation in accordance with an agreement between the Board of Directors of the University and officials of the Ethyl Gasoline Corporation. The Nature of the Lead Hazards. at an early stage in the use of gasoline containing tetra ethyl lead it became apparent that the manufacture of tetraethyl lead and the blending of the concentrated fluid for use in gasoline was a hazardous occupation with unique opportunities for the rapid develop ment of lead intoxication. The serious dangers of these manufacturing 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 nanufacture with the problematical dangers arising from the use of tne finished fuel, has persisted.. Therefore the distinction between them must be made clear. Hazards Associated with the manufacture of Tetraethyl Lead and Leaded Gasoline. Pure tetraethyl lead is a heavy, colorless, oily liquid which is retained with difficulty within jointed receptables and pipe lines. It is insoluble in hot or cold water, but readily soluble in alcohol and aceoone ana miscible in all proportions with fats and oils. As might be suspected from tne latter, it penetrates the unbroken skin. 0021822 3 Indeed skin absorption alone may result in the rapid production of acute illness and death in experimental animals (4,.5). From a physical point of view, the volatility of tetraethyl lead is low, but in toxi cological terms it is dangerously high, since at ordinary temperatures air saturated witn its vapor contains approximately 5 mg. of lead par liter. This concentration is lethal for rabbits in a few hours (4), a fact which demonstrates 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 warning of its presence, in that a very low concentration of these substances induces irritation of the rnucuus membranes with weeping and sneezing. The dangers associated with the preparation and handling of tetraethyx lead are fairly obvious,, when these properties are recognized. Unfortunately, this information was not available when the manufacture of the product was first contemplated. It is not strange,, therefore, that when the production of tetaethyl lead emerged from a laboratory scale into an incipient commercial stage, cases of lead poisioning odcurred, characterized by the sudden onset of cerebral symptoms and a high mortality. 'Without entering into a description of the various steps by which leaded gasoline is prepared for the market, suffice it to say that the hazards of manufacture are due mainly to tetraethyl lead. hi The hygienic problem at every point consists in the prevention of skin contact with tetraethyl lead, and in the maintenance of conditions under which its vapor is not inhaled. Because of the snarp locaiiza- they are amenable to adequate .control; neverthe- 0021823 4 only by continual vigilance. The extent to which lead absorption has been controlled in the manufacture of tetraethyl lead through the. .use of special equipment and tnrough the inauguration and operation of. suitable safety measures has been suown elsewhere (6). Hazards associated with tue Distribution and Use of Gasoline Containing Tetraethyl Lead. The nasards associated with the handling and use of the finished gasoline differ both in quality and quantity from those wnich occur 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 tne part of such gasoline to produce a substantiated case of lead 'intosication up to tne present (November, 1933) after more than 10 years of continuous use in certain parts of tiie United States and almost 8 years throughout the entire United States. (This basis of differentiation is tne more significant when one considers that the hypothetical opportuni ties for tne absorption of lead, as a result of the distribution of leaded gasoline, are so varied and so widespread as to defy regulation.) But there are other points of difference which did not require the test of experience for their recognition. Tetraethyl lead is introduced into gasoline in amounts so small that the solution lacks the essential toxicalogical properties of tetraethyl lead. Thus, whereas tetraethyl lead alone, or in high concentration in gasoline, is rapidly absorbed through txie skin, its absorption is retarded greatly by dilution in gasoline . Indeed we have been unable to obtain evidence of lead absorption through the skin of experimental animals after their prolonged exposure to concentrations of 1 part of tetraethyl lead per 1GCG parts of gasoline by volume (5). The dilution of tetraethyl iead with gasoiine also largely eliminates the danger of lead inhalation. 0021824 iLsiWii.iiisstf 5 Taa difference between the volatility of tetraethyl lead and the various gasoline 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 tnis fact, that the vapors rising from tanks containing leaded gasoline do not contain appreciable amounts of lead, however, tnis does not mean that no tetraethyl lead may be evaporated under any of tne practical conditions of handling and use cY spillage' of lead-containing gasoline. Although years of experience have not shown the existence of danger to the community in the use of gasoline containing tetraethyl lead, and although tne qualities of the fuel, as described above, ex plain this result in a large measure the possible lead exposure asso ciated with the general dissemination of such a product may not be dismissed lightly* A full appreciation of the opportunities for ex posure is required for an understanding of the problem which they provide for investigation. Leaded gasoline is handled at refineries, bulk 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 tnis motor fuel is dispensed tin:rough filling station pumps. In England a large amount of gasoline is distributed in two-gallon cans *V.e have found that no accumulation of lead occurs in rabbits as tne result of months of exposure for several hours daily to such vapors, in experiments in which the gasoline vapors were sufficiently concentrated to maintain the animals in a state of mild intoxication. wnicn are filled by automatic equipment at refineries and at storage points. Large numbers of persons come in contact with tne gasoline through, spillage, as an unavoidable result of the various methods of -also inhale vapors from tanks, hose lines and 0021825 o surfaces on wnich the gasoline is spilled. At refinery loading racks, at filling stations and at other points where gasoline is handled regularly, tne repeated spillage of gasoline containing lead may bring about toe accumulation of higher boiling petroleum fractions, and small amounts of tetraethyl lead, by reason of their absorption into wooden platforms r ot.sr surface materials such as concrete,, asphalt, gravel, cinders or earth. Under these conditions some portion of the titrae.thyl lead is evaporated slowly, and the remainder undergoes, decomposition. In either case, opportunity for innalation of lead on the part of persons in the vicinity may be provided, though, no doubt, most of the accumulations are dissipated by frequent nosing, or by rainfall. Under prevailing marketing conditions, the decomposition of tne tetraethyl lead in gasoline is almost inappreciable, but over a period of years, variable amounts of lead deposits may be found in the scale on the sides and at the botiom of storage tanks,.tank cars, and other containers. Attempts to clean these containers in a dry state may cause the innalation of finely divided dust containing triethyl lead salts. In general, the pfgcautions which are required to prevent tne innalation of dangerous amounts of gasoline are adequate safeguards against tne absorption of the lead deposits, but this potential source \ of lead absorption may not be ignored. The sale of the gasoline to the consumer takes it into the province- of the general public where some degree of exposure to skin contact and to vapors may occur. Of more importance, however, is the appearance of a new set of conditions based upon the combustion of the fuel. letraetiiyi. lead is converted, thereby, into finely divided inorganic lead compounds (chiefly lead bromide), which are deposited, in part, along the exhaust system, but which otherwise, are discharged K 0021826 7 into tne atmosphere with the exhaust gases of tne motor. The. extent of tiie accumulation of exhaust gases from many automobiles in busy city streets, and especially in poorly ventilated areas where cars operate in considerable numbers, becomes a question of importance. This aspect of vie matter concerns tne entire urban population, but it develops a special significance in tne case of garage mechanics. Garages, in general, are coo riy vent.il a ted. Few of them, indeed, are equipped to maintain an adequate dilution of exhaust gases under the most favorable conditions, ana v/nen doors and windows are closed in cold weather, ventilation is often negligible. For tnis reason, tnrougn tne winter months, many mechanics develop late afternoon neadacnes from the ab sorption of carbon monoxide. Their exposure to lead in tne exhaust gas of automobiles burning leaded gasoline is greater, therefore, than that of any otner group of persons in the community. Further, the hand ling and tne spillage of gasoline, the adjustment of carburetors, and t^e repair of other parts of the car often involve shin contact with tne gasoline and. with lubricating oil which may contain minute amounts of tetraethyl lead. Tne spillage and evaporation of gasoline may leave benind. tne less volatile tetraetnyi lead to be slowly volatilized at a later time, or to decompose, and by so doing to add to tue lead dust in tue garage. In tne dismantling- of motors the combustion products of tetraethyl lead may be encountered by the mechanic, and although these cannot be absorbed through the skin, they may be a means of contaminating ais hands, his clothing, and his surroundings. \7e must regard these factors, as well as tne deposited lead of the exnaust gases, as contri butors to tiie accumulations of iead dust within tne garage although tne amounts of lead involved are probably not so great as those which originate from the repair of electrical storage batteries and tne use of paints and solder in the repair of automobiles. One furtner point must be considered in a complete analysis 0021827 Vs:*. of one possibilities for general lead exposure in tne use of gasoline containing lead. The deposition of lead compounds upon the nighways, city streets, - in snort, upon the surface of the earth - may conceiv ably influence tne amount of lead breatned by animals and men, as .well as tne quantity incorporated in and deposited upon vegetation employed as food. Tne Distribution and Sale of `Leaded Gasoline in the United States. The cnaracter of tae lead hazards developed through the use of leaded gasoline is based upon the methods of its distribution and use. Ineir general magnitude is dependent upon the extent of 't^e distribution of suca gasoline, the volume of consumption in a given area, and tae period of time over which distribution and use have ex tended, ti.e:3 factors being modified to some extent by the variations in t..e lead concentration in gasoline, which have occurred in various sections of tne country. Gasoline containing tetraethyl lead was distributed first in tae early months of 1923 in Dayton, Ohio. A few months later it was on sale in Cincinnati and in the district about these two cities. Thence its use was extended to middle western and southern United States, into areas represented most satisfactorily by the cities of Chicago, Detroit, 3t. Louis, Jacksonville, Atlanta, and Savannah. The quantity of tni s gasoline sold up to 1925 cannot be estimated accurately, but it was limited to this general area, and there was a steady increase in the volume of distribution during this time except for a period of almost a year beginning in Lay, 1925. (At that time leaded gasoline was with" drawn from tne market pending an investigation of the United States Public health Service, though for various reasons its use was not interrupt ai in certain areas.) The expansion continued until this automobile fuel had become available in all parts of the United States. ..able a snows tne dates at which sale began in various cities of tne united States._ The duration of continuous distribution for taese areas X* 0021828 _a_ is also recorded up to tue time of tue observations wnich are to be described. The approximate quantities sold during the years for which figures are available are shown in Table 2. It should be noted that tue general areas into which the gasoline v/as first introduced main tained the largest proportional and gross consumption. in- Ohio, where the greater part of the early investigations were carried out, the concentration of tetraethyl lead in gasoline up to 1S2S was maintained at Sec. per gallon - approximately 1 part of tetraethyl lead in-J2 6o. pa rts of gasoline, by volume. In certain other areas, during this period, as little as 2 .cc, was used. Since that time, tue lead concentration has varied in accordance with the quantity required to bring the available gasoline base up to a definite standard of performance in a test engine, exeept that the amount introduced has not exceeded 3 cc. of tetraethyl lead per gallon of gasoline. The average lead concentration by years for different regions of tne country may be seen in Table 3. a brief study of the contents of these tables is sufficient to give a clear indication of the areas in which the greatest opportuni ties for lead exposure have been provided. They also yield a graphic concept of the proportions of the problem with which we are dealing. In the light of the information furnished by previous inves tigation, there can be little doubt that certain of the hypothetical hazards described above, do not exist. However, we snail disregard these details and deal, primarily, with one question, namely, - is the magnitude of lead exposure' arising from the combined hazards of the use of leaded gasoline such as to bring about appreciable lead absorption on tae _ art of any group of individuals in the community? K 0021829 10 3. Experimental Investigation. Tiie Selection of Experimental Subjects. Groups of subjects were selected for detailed study of tne effects of their occupation upon their nealth, and upon such physiolo gical processes as are specifically influenced by an increase in lead absorption. Table 4 shows the numbers and types of subjects, together with tne locality in which they were employed. The three groups of workmen who had experienced all the types oflead exposure associated with the use of leaded gasolineare represented by 56 filling station attendants, 5C tank-truck handlers of such gasoline, and 201 garage mechanic s,, The filling station attendants were chosen with attention to several matters: men who had been employed as subjects previously, who had been handling leaded gasoline for the longest period of time, who nad handled gasoline containing the highest concentrations of tetra ethyl lead, and wno had handled the largest amounts of leaded gasoline daily, were especially desirable. Until hay 1S25 a small metering device containing a liter can of Ethyl Fluid was used on filling station hose lines to treat gasoline with the lead mixture as required. This method of distribution brought about some degree of exposure to con centrated tetraethyl lead on the part of filling station employees. Therefore, those subjects whose employment dates back to this period have had opportunities for the absorption of leLd from this source. Trey 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, 3avannan, Jacksonville and Atlanta there had been no interruption in tna distribution.of leaded gasoline since its introduction. Fifth ermo re OE8IZOO 11 tils employment varnover of filling station attendants had been such that it was not difficult to find a satisfactory group of men who had dispensed leaded gasoline since it was first marketed from their stations, fee consumption of leaded gasoline has 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 filling stations had handled more leaded gasoline than had men similarly employed in any other part of the country. The tank wagon handlers were selected on trie basis of the severity and length of their exposure to leaded gasoline. Twenty-four of them had served as subjects for study in 1987* Thus a direct corntarison of the results obtained on the two occasions was made possible. Tae garage mechanic group was made up of 1C9 persons wao had been woraing on cars which used only leaded gasoline, and an additional 93 who had been repairing cars of which a high percentage used such gasoline. effort was made to find ail the mechanics in the United States who had experienced prolonged exposure in garages in which all the cars had used leaded gasoline exclusively over a period of several years. Ten members of the group had been employed in a public service garage in Dayton, Ohio, in which only leaded gasoline, had been used from 1923 to the time of the present investigation. Thirty-nine subjects had had from 3 to 6 years of daily repair work on cars in which leaded 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 occupational relationships to leaded gasoline. The garage . . ,,+ ? *m onp^iai o on s i d e rat'i-o'n-..'atn-c-ew it is com- K" 0021831 posed of men wuose occupation combines all the potential lead exposure derived from tne gasoline in an intensified form, together with certain otner lead exposures uni oh are not related to gasoline. For this reason it was expanded to a large number at the expense of less exposed groups. The barrel-fillers referred to in Table 4 are included among the sub loots for a specific reason which will appear later. The data are available through a fortunate coir,bination of circumstances. Several yei rs of observation of persons wnose occupation involved considerable exposure no gasoline had aroused our interest in the influence of proionged gasoline absorption. Accordingly, a search was made for a group of subjects whose exposure to gasoline was severe and uncomplicated by otuer occupational factors. In the summer of 1925 such a group was found in a refinery in which large quantities of gasoline were put into fifty gallon barrels for transportation. The barrels were filled in a specially constructed room provided with forced ventilation. Despite the magnitude of ventilation the concentration of gasoline vapor was nigh enough to be immediately disturbing to one who was not accustomed to such vapor. In addition, the skin, clothing' and shoes of the workmen were frequently and almost continuously wet 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, -.nd the valve was opened. Gasoline flowed in at considerable pressure until the level of liquid in the drum released tne valve, thus closing ip. Occasionally the valve refused to work properly, at which time a stream of gasoline rose from the 4,rum and thoroughly Irene..ed any workmen in its immediate vicinity. " 0021832 Dav 13 T:ie number of men engaged in filling and handling the drums of gasoline was small but one severity of exposure was such a s to give excellent opportunity for tae detection of any effects which might result from gasoline absorption. These men were carefully examined in a manner wiiicii will be described later, and several types, of labora tory data were obtained, including the lead content of the urine and feces. (.The 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 leaded gasoline. Tae latter was handled in the manner described above for ordinary gasoline. Inasmuch as experimental evidence indicated that the hazards of iead. sorption from skin contact and inhalation of vapor from gasoline containing: tetraethyl lead were practically negligible, no fears were en tertained as to the consequences of the additional factor of a low concintration of tetraethyl lead, nevertheless, tnis constituted a unique severity of exposure. Therefore it was considered advisable to obtain information which would show whether or not the men were absorbing lead. accordingly, at the end of a period of 6 months, during which leaded gasoline had been handled daily in the previously described manner, tae workmen so employed were examined, and samples of their excreta were obtained for analysis. In this second group, made up o.f 22 men, tae re were ten who had been included in the first set of ex aminations. Except in the case of the barrel-fillers, comparable groups of subjects unexposed to t.,e potential dangers of leaded gasoline, were not obtainedyfor study. At the time of the study io r1 s \/&s no o.r H r 0021833 of tiie United States in which the selection of entirely unexposed subjects could be made, since the use of leaded gasoline had increased sc) as to involve all parts of the country. Therefore it was necessary to re1y on informat ion obtained prior to tiie general di stribution of leaded gasoline, for comparative data on similar groups of subjects independent of this factor. On the other hand, since re peated observations had been made on the same individuals under condi tions of continuous exposure, tne successive findings furnished a means for tne discovery of progressive effects of any type. Experimental Uetnods. Experimental studies on animals and men have established the existence of a relationship between the magnitude of the lead exposure and absorption and the rate of lead excretion, in that fecal excretion is a ..teasure of ingestion on the day preceding the collection of the sampa e, v.nle tne urinary excretion indicates the magnitude of lead ab sorption (o, 7, 6). Nevertheless, we wished to leave no stone unturned waich might yield additional information. Accordingly, we searched for clinical evidences of lead absorption with tae samd cars that we applied to the collection of accurate analytical data. Care was taken to obtain all the information possible from eaca subject, and to record such informational an uniform manner. For this reason cards for recording data were provided as reproduced in Figures 1 to 5 inclusive, and the work was divided among four physicians each of whom carried out tiie same type of observations on eaca subject. k Co far as possible 'quantitative information was obtained in the physical examination, but without the subordination of clinical judgment. Thus while it was recognized that a statistical study of all the data was --v'a-' -'ai inioal diagnostic methods as. applied -.to. individual oases 0021834 were regarded as of greater importance in determining whether or not ) an? evidence of lead int.oxicat.iori. rad appeared among tne subjects* a s an example of tuis goin' p p p c a subject was tested for evidences of A.;.rQony or muscular weakness by palpation and oy opposing tre exmi ner' s strength to taat of tne corresponding muscle group of tre subject, rut for tv.e purposes of statistical comparison of a single neurormuscular factor, tre grip was tested by a hand dynamometer. (The same instrument was employed, taroughou t the tests.) measurements of the blood pressure of esc., subject (seated) were made with a standard maaometrie apparatus. A fresn specimen of urine was obtained fro mi eaca subject and examined, at once for its reaction, tae presence of albumin, and sugar. Macro scopic examination of the urine and a test for acetone were carried c u o/:i " x l \-j .l o .1 x c 'i oy o.iCiniCai & o h o nutix i 1/ i s3 s or by su^26suivo clinical findings. Erythrocyte, leucocyte and differential leucocyte counts were .iiade/a routine procedure only on the barrel-filler group of subjects. Otherwise, such procedures were followed only \msn indi cated for diagnostic purposes. Hemoglobin determinations were made on eacn subject by means of trie Dare hetnoglobinometer. A single instrument was employed for all observations, and ail readings were maae so-uis observer. Blood smears were made on all subjects, and were examined for stippling of trie erythrocytes by a standardized metnod which wixi be described elsewhere by L. Y. Sanders. Samples of urine and feces were obtained from the sub jects for the determination of their .-lead content. Tne collection of these and t..e analyses were carried out according to methods which we aave described previously (9). In a few instances no samples were o c t a i na bx e. further smaxl number of samples were lost in transit and in process of analysis. Ti'ith these few exceptions, the analytical v-acn i t.? wereAdbtained without difficulty. K 0021,8.35 15 4. Experimental Findings. ::o e-css of leu d intoxication was found among the subjects, In fact,, no combination of symptoms and physical findings wa.s suggestive oi iDtOAics ijion* c ucu evidences of lead absorption as are common among 1 e . d workers were censpicously absent. Of special negative clini-' cal importance were tne complete absence of lead line, the lack of significant, microscopic- blood changes stippling), and the infrequency CI V 0U e 3p wp COWS a i in health. Under these circumstances any evidences of significant lead absorption as a consequence of exposure to leaded gasoline- ,.,ust be sought in the data on the excretion of lead. Pertain of tne clinical findings and all of the analytical data for the groups are presented in a series of tables which represent c..e exact -manner of tne statistical study except as otherwise noted, onerous other clinical items which were subjected to statistical analysis, nave been omitted because of their negative significance, and for the sake of brevity. fable 5 snows tne classification of the subjects according to the duration of taeir exposure to leaded gasoline. One-half of tne filming station attendants and a little less than half of the tank wagon handlers had been exposed for 5 years or more, while 69 per cant of the garage mechanics had repaired c . rs which lased leaded gasoline over a period of 3 years or more. Y,rnether or not it has any bearing on jthe problem at issue, tne occurrence of previous industrial lead exposure among tae subjects may .not be ignored. Information on this point obtained from the occu pational histories is shown in Table 6. Here it may be seen that a i-rge proportion of the subjects had been employed in trades which involved spite ,opportunity for lead absorption, prior to their exposure . jy recj r-a p mechanicsymaix...be.\,regarded as 0021836 from tne factor of leaded gasoline. However, it may be assumed that few garage mechanics Have more than a slight iead exposure in tiie sours of their normal day's work, since small jobs of soldering and painting and one occasional repair of a storage battery Have not produced a noticeable occurrence of 1eui intoxication among garage mechanics . One tank wagon driver and 3 garage mechanics had been employed at some previous ti>..e in hazardous lead trade-, in vmich the i r exposure had not been aeve re either in quality or duration. The distribution of the subjects according to age, seen in Table 7. is significant only in that it demonstrates the inclusion of vidag- varying age groups among the subjects under investigation. In Tables 3 and 9, the findings as regards haemoglobin of' tue clood, and stippling of the erythrocytes are recorded. Mo mean values we re computed for tne occurrence of stippling by reason of the nigh proportion of negative results. It may be seen from the tables tn~ t no significance may be attached to variation in these matters in relation to leaded gasoline exposure, since practically all -the findings art v.ituin normal limits. However there is a high frequency of low hemoglobin readings and of abnormal numbers of stippled ery throcytes among the barrel-fillers exposed to ordinary gasoline. These men were examined in the summer wnen inhalation of gasoline vapor was at its h eight. Apparently, exposure to gasoline vapors may produce blood changes, including the appearance of stippling. Tue facts obtained from the analysis of the excreta of tne subjects arc presented in Tables 13, 11, and IE. A survey of the tabu lated results shows that a few high results are scattered irregularly tnrouwa the data. 'There these occur in fecal smaples it may be assumed that tae.y have.Resulted either from contamination of the s-.mpie or from HE 0021837 t..e in:a e lion of unusual amounts of lead with food material, and tnat tnay nave no necessary or probable relationship to occupational lead exposure. The inclusion of such, findings in the 'computation of mean values increases appreciably the probable error of the mean, and mili tates against satisfactory comparison.of the groups of subjects, never theless, suca results nave been recorded, and have been included in the calculations unless otherwise specifically noted in the tables. Where a result has been excluded it has been for the purpose of eliminating a finding v/nic a has no probable - relation to the probl em at issue. In tne esse of tne urine samples, aberrant results are of rare occurrence, as would be expected. On tne other hand, contamination of an occasional sampie luring tne process of collection is apparently unavoidable, des pite tne .lost careful instruction of the subjects. This is not remarkable ..hen tue ubiquity of lead compounds is appreciated, and when tne lack of understanding of caemical cleanliness on the part of the subjects is tj.xen into account. Tixe analytical results serve to classify the various groups of subjects as distinctly outside the hazardous lead trades. XCompare with data from certain lead trades (6))* At first glance, t.:e ...ear values for tne lead content of the feces of filling station employees, tank wagon handlers and garage mechanics seem nigh, as compared to those for normal persons with no occupational lead ex posure. On the other hand, the small group of barrel fillers who were not exposed to leaded gasoline, and who had no other occupational lead exposure at tne time of the examination, show similarly high findings. Furthermore, when Che fecal lead is expressed in quantitatively comparable terms, (in milligrams per gram of ash), the apparently high Kf 0021838 -19results lose their significance. Finally, for reasons whicn we nave pointed out elsevnere (6) it is impossible to draw exact conclusions as to t-e magnitude of lead absorption, from tiie results obtained on samples of feces, and it is necessary to resort to tiie study of tne urinary excretion for such information. As judged by this standard, tne groups fall into tiie category of persons lacking occupational exposure to lead compaunds. A special significance is attached to the failure of the barrel fillers to show any increase in their lead excretion as a con sequence of their exposure to leaded gasoline. Not only do the two groups fail to differentiate themselves from the point of view of lead excretion, but it is equally true that no single individual in the groups can be differentiated. Of the 10 persons who were examined prior to exposure to leaded gasoline, and again after 6 months exposure to leaded gasoline, no person shows an increase in his rate of lead excretion. This can be interpreted only as meaning that there was no significant lead absorption as a consequence of this exposure. Thus, it seems quite clear, that the. inability of animals to absorb measurable amounts of tetraethyl lead out of gasoline in dilute solution (5), (1 part per 1000 by volume or less) is shared by man. 5. Comparison of the Findings with. Results Obtained Earlier. In view of the importance of the conclusions of the above paragraphs, indicating the negative character of the findings, it is proper to present observations of a comparable character on groups of subjects similar in every matter save that of exposure to leaded gasoline. Accordingly, Tables 13 to 13, inclusive, show results obtained in 1927, in a study of groups of persons who had not been exposed to t^e conditions associated with the use of leaded gasoline. Tne medical student group is composed of members of a newly matricu lated class. For tae second group, filling station attendants and bulk: handlers of, ordinary gasoline are combined in--order to make a 0021839 -So laris group for statisticai purposes* Unfortunately, no analytical data are available in one Case of fne bulk handlers of gasoline, because of tnsir unwillingness to provide us wi.th samples of their excreta, and therefore t..e analytical findings relate only to filling station attendants, as indicated in. the tables. The control garage mechanic group is made up of only a small number of men carefully selected in 1926 as lacking any exposure to leaded gasoline. The rigid reg.irements in the latter regard introduced considerable difficulty into t.iS problem of obtaining cooperative subjects. ho explanatory comments are required, since tne tables present tne observed facts adequately. It siioul d be pointed out that, ti.e observations recorded in these tables were made by the same persons wv.o col - sot :-d tne d.-;ta on t-..e exposed subjects previously described. Tne clinics! methods employed in the two instances were substantially the same, while the analytical methods were practically identical. Table 19 summarizes the mean values for all the groups of exposed and. unexposed persons, in such matters as would seem to have special significance. (Since the frequencies of occurrence of stippling do not lend themselves to computation of mean values, comparison of this important factor must be made from the tables of distribution.) Comparison of the means reveals a lack of statistical differentiation of the groups* The medical students show a significant difference in age, but in no other factor. The barrell fillers not exposed to leafed gasoline snow a significantly low hemoglobin content of their blood, as previously pointed out. The in ..-an lead content per sample of feces also snows certain statistic hly significant variations within the groups, but no actual importance can be attribute' to these differences in view of, ;the .variabil i t,y in tne size of the fecal samples. ..'hen the KE 0021840 21 lax,ter factor is corrected by expressing the lead in the feces in relation to trie quantity of ash, the variability of the g'roups is statistically insignificant. The influence of rrevious Occupational head Exposure. It has been intimated that some significance may be attached to trie fact that a considerable number of the subjects had been exposed tr lead compounds in previous occupations. Likewise the handling of lead compounds other than those associated with leaded fu el * ...i rut ca expected to nave some influence upon the lead absorp tion of the garage mechanic. As a means of ascertaining the import ance of t.:3se matters, the analytical results derived from two small groups of persons those occupational histories failed to give evidence 0 i* u y j J j q i. ^ ct d >3 x "0 0 SXa re, were subjec ted to study. (Table 6 h a s .;ix 3.03 d i s 0rI bu ui on GI t: i e 3U b J s c t s a s to orevious occuo ational i. 3 r.A J 0 j i _p- G 3 .X r 3 / - ci G X 3 -GO presents the 1.1 e a n values for the 1 ead excretion of these subjects as separate groups and in combination, fae results are seen to be slightly lower, but no significant statistical differences have resulted from the exclusion of the orevi .usly exoosed subjects. Lead Excretion in Relation to Length of Exposure to Leaded Gasoline. an examination into trie relationship between length of service and lead excretion, might provide a means of ascertaining 0021841 the significance of tue lead exposure associated with the occupation of tue garage mechanics. This was done by studying tiie correlation between the magnitude of lead excretion and the period of continuous employment as mechanics, and then by a corresponding study of trie magnitude of lead excretion in relation to length of exposure in repairing cars which used leaded gasoline. The results of these attempted correlations are s.-.wn in Table 21. There is a complete lack of..correlation in either matter. From these rresul,ts. one must conclude either that tne lead exposure associated with, the occupation is insignificant, or that it is nf such irregular occurrence as to .. -y j no measurable title relationship. There remains one other means of examining the available d;ta in search of evidences of lead absorption from the handling of i.eaiei gasoline. among the subjects studied in 1929, there were 25 filling station attendants, and 24 tank wagon handlers who had been employed as subjects in 1927. Presumably, if their occupation con tained a significant lead hazard t..ey snouid snow some evidence of Change in *3ad excretion after 2 years. The findings for the two years, as to j. ea d excretion, are snown in Tables 22, 23, and 24. The mem values are summarized in Table 25. Ko statistically valid differ ent e is demonstrable. S. Summary and Discussion, Tnree hundred and one raen who had incurred tme severest and longest exposure to leaded gasoline and its combustion products were studied as to tueir physical fitness and taeir lead excretion, during tne -..inter months of 1929-30* No clinical evidences of lead absorption or of i8ad intoxication were found in any individual, and no indication of lead absorption, as a consequence of the.exposure, was detected when. t..e subjects were compared as to their lead excretion with corres ponding groups of unexposed persons who had been studied previously, -moreover tnere was no measurable change in the lead excretion of a group of fifty of tae subjects who had been Studied in a similar manner in IS27. The lead excretion of a number of workmen was determined ora and after a 5 morn period of intense skin exposure to leaded gasoline, ho individual in tae group showed an increased lead excre- 0021842 ;o - Lion tne period of exposure. lus xevel of Human lead excretion has been shown to be highly ser.sitive to t.^e magnitude of lead exposure and absorption (6,8) , and sim ,s f.ailed to snow an increase in their lead excretion, it is . arent xgo uit,tle exposure to lead existed, and that no sig* nificant ui 0 S C h*' i G n of lead uis-.ed fi 1~: -A 1 n Jl 3 c; o oO tiie 1 persons ( 5 - J , -- iUu S ty G 0 r of ia. ' i iiw "^ion with food 3 sufficient to mask a slight lead ab- so rp tion ` ~ -\ ~ , _j ; * `" v- result f t-.e use of * eaded gasoline. exposure to the conditions arising from If this has occurred, the relative insig nificance of tne contribution made by leaded gasoline to the total lead absorption of tne experimental subjects is obvious. On the other hand, t..e tec-.nie employed in tne foregoing observation should be modified so as to control the factor of individual lead ingestion on the part of s a -..osec versons, i 1 ih e precise m a gn i wuus ox tne occuoaoionax x e a o e a -- posure is to be measured. Y.'e shall present the results obtained through tne use of tne latter method of study in a subsequent article. In view of tne negative evidence obtained in this stud;/ of persons whose exposure to leaded gasoline and its comb.ustion products was magnified to a point well above tn&t which is possible in the venerax population, there is no reason to fear the existence of danger :udiic health fro fa the distribution and use of leaded gasoline. K 0021843 - 24- references Sayers, R. R. et al: experimental studies on the effect, of Ethyl Gasoline end its combustion products, U. 3. Bureau of mines Publication IS'27. Leai-ce, J. F., et ax: Tue u-e of tetraethyl lead gasoline in its relation to t..e public real tn. U. 3.Public Keaxth Bulletin No. 1.33, 1325. Ninel Report of the Departmental Committee on Ethyl Petrol; ministry of healtu - London. 1930. Hence, _I' pw' - KS <_ vA* FU a .* OHni tne tonicity of tetraetayl lead and inorganic i ead s "*.x jb ^ b T tX b. o.: Clin. mod. 12: 554, 1927. Keno e. Robert . ; a nndd Tnamann, Frederick: The behavior of lead in *a.-* a: . it,.ai ortanis la j.I i e v^raetayx xe:.dj am. a r. ^.yB- ene, 13; * '7 -J "i 9 31. : t . *. ? j Robert A., T . Frederick, and Gaol ah, Jacob; Lead C G o r '0 tion and eexx'ccrreettiioi n in certain lead trades. Jr. Ind. Hyg, i O .m o 5, 1933. B eno a, Ho o .7 r t . , and ' W.4. C! _tl i lmax orgnnis t : Am. Jr. Pub. Health, 10: 555, 1923. if eno e, Robert A., mi.Uc Uu . in, Frederick, and Ciioiak, Jacob: On tils i iO rinai ab sorttion and . icretion of lead. II Lead absorption lead excretion in iwOG & i am. life. Jr. Ind. Hyg. 1_5: 273, 1933. O 6 ji\ Qj l x -m o 6 r t A, j iiid ui. n, Frederick, and Cholak, Jacob: On th; no rnal b. o o r; t i on an o .c ret ion of lead. I. mead absorption and excretion in primitive life, Jr. Ind. hyg. 15; 257, 1933. K 0021844 1 I. period Of Distribu tion of 3 3 abed Gasoline in Various American '~ 4 t i 0 S w7 to October 1929 _ocaliv- "'ate of " i r s t Si st ri but i on T y-\ terval of -- 1 scontinuance Years 0 f Continuous t'i st ri but ion Davton, Ciii o Cincinnati, 0. .Vneelin.c, `.7. Va. Cia i ca-'?o, T2 I. 1 u, - iC.ii -- L> "*v -- ---.v f pwt * ' f - ri -u * c: % - - - ` q * ... . 4 4 Februarv i 9 S3 ' v- ' IS 23 none none ; ;., _:.(r y. .-.0: too on - '.O-.', >`i i 30 ri '3 - i 9 :33 1 C: T' uT - o'1/ x3 3o t* o summer x 3 85 It ri a : It j - a 11 it it :i 21 1924 ;3 It ft `1 1924 It W -if fori no; 19 34 A A ?* '.*? It 5.7 6.5 3.2 3 pCV Q I _ tC O 'F'. * -OV3.2 3.2 Sorinr Baltimore, Ad. Spring iias.i l n '-'ton, a, v. Lp rin/f 19 24 19 24 19 24 11 M W 11 H J3 *1 W ' !* It 14 11 it 3.2 3.2 -7 Q O * i-j San Antonio.Texas 3 or inn 19 24 1* 11 :t 11 3. 2 -- X TJ ^ ^ <2. "'L ^ autumn 19 24 none 5. C Jr\ X* X 3. j"i b "A , ' 7 cl * Autumn 1 9 24 11 5.0 Jacicsonvili e, Fia. Autumn 13 24 I? 5.0 14ew 0rleans, La. Sorinr- IS 35 W 3.2 ^1 0vsldnd, Giiio ^u inine r 19 86 3.2 X- j. 1 -L -v . L. -L il l cL ^ i, <3. ^uiHiier .19 25 11 3. 2 ' l OSIOl . i.dS. 3 3 Denver, Solo. OOOiCaiic , v; ri 3ij . UiSa , vic J. a, bummer Summer burnme r Summer 1926 19 26 19 35 1925 fl n n n 3. 2 2.2 2.2 2.2 San "ranci sco, CaL '..'inter 19 25 n 3. 3 j--< o 5 . i11 X c* ( O cL i Winter 1985 ' 2. 8 K 002184-5' 0021846 > a o x p <3 CD Cl 3O co CD a a o P 3 P Hc+ai <J C+ CD JO c+ O CD O CO 3 CO 31 3 3E O hG 3 ci-+1O CD 5 CO G> O ^5 C+ o f-1 CD OP o a. i* CD O GO oJ CD CD 3P CO oo t->5 [ - i--' W3 CO CD CO CO H>- 3 < P 3 (- o 3 CO tl> 3 CD p CO o c+ 3" CD o 3(-> c+ CaD TABLE ft 3 .average Tetra-etnyl Lead Content of Gasoline in Various Areas of The United States from 1926 to 1929 3 t w U i w o - ; j u w 3 S . e * and and dew York: y3 s A v^ra te .1 \> 3o Tetr^aetin/T Le ad 19 27 Content I ! in Cubic IS 25 Centimeters i 19 29 r .......... \ per.Ga 1.4 > 1.1 i 1.2 1 0.9 Rennsyiv nia Atlantic Coast States 1.2 1 1.7 : 1.0 1.6 1.2 1.4 1.65 i i 1.5 Ohio O.S 1.2 1.1 ? 1.5 Kentucky, Georgia, Tlorida, hiss. and Alabama j iii r Louisianna, Arkansap 'entrai States i l.G 0.9 1* 1.7 C .6 1.6 1.7 0.9 : 2.2 ; 1.9 / 1.3 ! 2.0 Texas an: O'iCx cl i 10 tAd Rocky fountain States 1.4 f 1.3 1.7 2.0 2.0 i 2.4 2.7 2.4 Lest Coast O l> d u c: is 0.7 1.5 1.5 United States as Anoi e 1.4-::- 1. S-: 1.75 1.62'... *" Tn e s e f i gu re s are est i to a t ^ s on i y - an d --may.-be....somewhat in error. ............ . HE' 0021847