Document 913Ybq6KbgwoGdVgVKemLR6YD

"A /r/TSU A < . THTRA-HTUYl, JM A II II AM !.TON HT AL. ..Tvals of ihrcr months, six months, aflcr, in 1021, Mason of f iiK'ioimli omfirnicd m;iiiy nf ,ik: aim! one-half years, in each case the Ifaniaf'k's findings, using various sabs of triuhv! and .re negative, tnmofhy! lead. Tim most important features of these c o m u MOMS exjxiriments arc: a stimulating action on the central The results reported show the practical value of scarfa fever toxin used in skin tests for susceptibility and active immunization for the prevention of scarlet fever. It has been demonstrated that the toxin may he administered with safety in doses large enough to confer complete immunity. Active immunity is developed within two weeks, and it lasts at least a year and a half, nervous system, mainly the medulla and higher centers; a marked stimulation of the central motor nerve mech anism, evidenced by trembling, twitching and, finally, convulsions, but without loss of consciousness; an extreme fall of blood pressure, apparently central in origin, for it fails in pithed animals; changes in the res piration, which at first is stopped, and then accelerated and deepened; slowing of the pulse, and increased peri stalsis with colic and diarrhea. The symptoms sep|ip by tetra-ethyl lead, in animals .and in human beings, bear a striking resemblance to this # TETRA-ETHYL LEAD ALICE HAMILTON, M.D. 'description, as can be seen in the report of a study of the latter recently completed by Eklridge/ of the Chem ical W arfare Service. From these experiments it is also BOSTON evident that tetra-ethyl lead can be absorbed through the PAUL REZNIKOFF, M.D. skin and through the respiratory tract, and that fliere is AND a cumulative effect when repeated sublethai doses are GRACE M. BURNHAM administered. Director, W orkers 1, Health Bureau Briefly summarized, Eidrklge's findings are as fol NEW YORK lows : Experiments on six dogs showed that application (. A new problem of public health and of industrial hygiene has suddenly arisen -in this country as a result of the addition of tetra-ethyl lead to motor car gasoline. This procedure was adopted about two years ago, but it did not come to the knowledge of the general public until last fall, 'when a number of men were poisoned in a New Jersey plant and five died. The distressing details of these cases of insanity and death and the unknown nature of the new poison aroused much excite ment and alarm, and induced the public health officials of New York City and of the states of New York and New Jersey to forbid the use of "ethyl .gasoline" on the ground of danger to the public from poison contained in exhaust gases of motor engines burning'such gaso line.1 This prohibition has recently been rescinded in the two states, but is still in force in New Yot'k City, of tetra-ethyl lead to the shaved skin of the abdomen resulted in a direct action on the intestinal tract, charac terized by acute lead colic, followed by diarrhea, the abdomen tense and painful to pressure, then depression, difficulty in getting up on the legs, tremors,- coma, con vulsions and death. The lethal point for dogs by skin absorption was found to be 0.3 ex. per kilogram of body weight.'"' Death followed in four dogs after from twenty-four to 180 hours, two recovering. In eleven guinea-pigs the lethal amount was determined to be 0,6 cx. per kilogram of weight, and death came on in from twelve to sixty hours. Three of this group recovered. The symptoms were similar to those in dogs. Inhalation experiments were made, on mice, five ani mals being used for each of ten concentrations of tetra-ethyl lead. The exposure lasted ten minutes, and Public excitement soon subsided, but a large and con tinually growing body of mechanics now organized In the Unions of Automobile and Aircraft Mechanics, Teamsters and Chauffeurs became increasingly con cerned over the possible danger to them, working as' during this time the mice showed activity, followed, after removal from the test chamber, by marked excite ment, then depression, collapse, trembling, convulsions and death. The lethal dose overaged 5.11 mg. per liter of ai r. they do in an atmosphere of exhaust gases, and, finding To determine possible cumulative effects, a 4,08 kg. a dearth of authoritative information on this phase of the matter, they applied to the Workers' Health Bureau for advice, The present report was compiled from the available data at the request of the Workers' Health dog was chosen, and applications of 0.1 c.c. were made to his skin once a day. After the twelfth application (lie dog became depressed and nervous, and increasingly so until the eighteenth, when he became unsteady on his Bureau and with the assistance of the bureau. feet and trembled. He died forty minutes after the Tetra-ethyl lead is added to gasoline to eliminate the "knock" or detonation in internal combustion engines. A halogen "carrier," either ethylene dibromid or trichlorethylene, is added, and during combustion decom twenty-first application. The cumulative action was aiso tested on mice, by inhalation experiments, exposing ten of them to 0.5 mg. per liter of air for ten minutes a day. Five died, on the fourteenth, to the twentieth days. position occurs, with the formation of lead chlorid or Necropsies on the dogs dying with acute poisoning lea^l bromid, together with lead sulphate from the sul showed an acute inflammation of the small and large phur in the gasoline and also small amounts*of lead oxid intestines, with numerous ulcers from 1 to 1.5 cm. in and metallic lead. The problem, therefore, concerns diameter, clean and punched out, with a smooth base. two distinct dangers: that of tetra-ethyl lead itself, and These were chiefly in .the i'egion of Peyer's patches, .that of the feagi products resulting from its combustion. which were swollen and prominent. One animal had a similar ulcer near the pyloric end of the stomach; one TOXICITY OF TETRA-ETHYL LEAD had no lesion in the intestinal tract at all. There was HarnackA in 1878, tested the toxicity of triethyl lead 'no change in the heart, lungs, liver or spleen, but a mild and its acetate on frogs, rabbits, cats and dogs. Years congestion* in all zones of the kidney. Analyses were !. An editorial in T he J o u r n a l , Nov, *8, 1924, p. 1531, called a tt e n tion to tetra-ethyl lead as '`another industrial hasard, " and. n f t t r com- eniing briefly on a number of fatalities among the producers of this substance spoke also, of ..the possibility of poisoning from (he exhaust ga-;s of motors, particularly as lead ib a cumulative poison. 2. Harnack: Arch. f. exper. Path. u. Jlharmakol. O : 152, 1878. a. mason, k,. s,.; t o e imarmacoiogtc Action ot Lead m Organic Combination, J. Lab. & Clin. Med. <J;427 (M ay) 1921, 4, Eld ridge, W. A.: A Study of the Toxicity of Lead Tetra Ethyl, Report 29, CSiemical W arfa re Service, Oct. 5, 1924. 5, O r 0.498 gm, per kilogram of weight. One cubic centimeter of pure tetra-ethyl lead weighs 1.659 gm. J MM2 f h . I t t J l ' . i i m , U' . At ) H A M I L T O N h.T AL . .I'HHI, A mav i,6,Mm. Ai// mu<!<' o f c x c rc ! ions, organs au<f hones of <!oi.'> and Eldridgc.'s paper contains a summary of (he symp*|| guinea-pigs, and lead was found in both unne am! feces, Puns in fix- Standard f fil cuses, as reported to thef iii -T c lrtu n , infeslin es, fiver and Umgs, tiy far (he largest company hy W. ( iiiinan Thompson and A, W, Schoen-j amount being in the skeleton.1" K ld rid g c comments as Iclier, Mav id, PHI. The first symptom noticed is a. fo)|i i\V': marked tall in hlnud pressure, sometimes Of) mm. o;| We arc (leafing wit!) a highly lipoid-soluble lead compound, which is capable of skin penetration and which, furthermore, is comparatively stable, ft is probably the only compound which, absorbed through the skin, causes acute lead poisoning. mercury below normal, an accompanying fall in bodyjt temperature, which has been as low as 94.6 F., and zM low pulse rate, down to 48 a minute. Then symptomspp of profound cerebral involvement appear, persistent"^ As a preventive.' washing with, various substances was tried. Although common soap and olive oil were both found to work well, the best agent was kerosene, followed by tincture of green soap. Animals so treated survived even if thirty minutes elapsed before washing the skin. This is EMridgc's summary: insomnia, extraordinary restlessness and talkativeness, and delusions. The gait is like that of a drunken iran,jf but there are no paralyses or .convulsions. F inallyJ| after a period of exaggerated movements of ail th e || muscles of the body, with sweating, the patient becomes.f: violently maniacal,- shouting, leaping from the' bed/! smashing furniture, and acting as if in delirium If tremens; morphin onty accentuates the symptoms. Thelj H is quite evident from these observations that the manu facture, handling and distribution of lead tetra-cthyl Involves considerable danger to operatives, of acute lead poisoning in those instances where considerable material is splashed upon the skin, and of chronic lead poisoning from the -absorption of small amounts by inhalation, by the skin or by the mouth. patient may finally die in exhaustion, in two fatal 1 cases, the body temperature rose to 110 F. just before: death occurred. One of these was a young man of A fine physique who had been at work only five weeks.'! He is said to have suffered terrible,agony.- "He diedff yelling." T H E PRESENT-DAY PROBLEM There are four questions that must be answered before we know whether, the manufacture and distribu tion of tetra-ethyl lead and its use in gasoline carry with them a danger serious enough to warrant prohibition by public health authorities. h The danger to men engaged in tire manufacture of tetra-ethyl lead. There is no cyanosis or dyspnea; there may be ver tigo, and the acute outbreak may be preceded by a period i of anorexia, vomiting and diarrhea. Changes in the r e d * blood corpuscles are marked, and the blood of one of;! the men who died failed entirely to coagulate. It hadJ[ the color typical of carbon monoxid hemoglobin. In oiie'1| | ease the systolic blood pressure dropped .from 190-to.M 112 mm. of mercury in three and a half hours, a. faHtfl commensurate with that following a severe hemorrhage/^ 2. The clanger to men handling ethyl fluid. This is a mixture of tetra-ethyl lead and ethylene dibromid or trichlorethylcne, with the addition'of a small quantity of dark colored dye. Ethyl fluid is handled by employees in the production plant and by distributing and filling station employees, who mix it with gasoline. - 3. The danger to men handling ethyl gasoline. This js ordinary gasoline to which a small amount of ethyl fluid has been added, about one-half teaspoonful to the gallon, 4. The danger to the public from breathing the exhaust gases from engines using ethyl gasoline, and the danger to garage workers, chauffeurs or other per sons who work on engines, exhausts or mufflers of motors burning ethyl gasoline. 1. The Danger to Men Manufacturing Tetra-Ilthyl ArW.--Within the last seventeen months, eleven men have died and. one man lias become insane through tctra-cthy! lead poisoning. All were engaged in the manufacture of this compound. These, accidents occurred as follows: Convalescence- is slow, and may take from six to ten,j l weeks, .iyM From the du Pont de Nemours Company's physicians,/ Eldridge secured a report of the symptoms in twenty-- eight cases of tetra-ethyl lead poisoning. The most y* frequent finding recorded is insomnia (twenty-eight^ times) ; then follows a markedly lowered blood pressure(J (tw enty); a subnormal temperature (nineteen); ano-. Jrexia, nausea and hyperacidity of the urine (eighteen);.! bodily weakness (sixteen) ; abdominal cramps (tw elve); unaccustomed and annoying dreams (eleven) ; vertigo el and morning vomiting (ten ); decided loss of weight.:j| (nine), and a slow pulse, increased muscular reactionsJp -Ifand headache (seven). Other less frequent findings were a metallic taste in the mouth, treniors, a lead line on the gums (in four cases), and itching of the skin.jig Lead was detected on the skin of twelve men. i'-i The accidents in New Jersey and Ohio were followed by investigations on tire part of the state officials, to /., determine the extent of the danger in tetra-ethyl lead production and the possibility of protecting workmen against it. Sept. 21, 1923, one death, E. 3. du Font de Nemours & Tire conditions in Ohio were inspected by H, Ehret | | _ Co., Carney's Point, N. J. of the Factory Inspection Department, and Dr. Nelson A ll June 1, 1924, two deaths, General Motors Research Cor C. Dysart. They found that at the time the two fatal''fflr poration, Dayton, Ohio. July 14, 1924, one death, E. 1. du Pont `de Nemours & Co.. Carney's Point, N. J. Oct. 20, 1924, otic death, E, 1. du Pont de Nemours & Co., Carney's Point, N. J. Ocg 28-30, 1924, five deaths, Standard Oil Company, Bayway, N. J. Pel). 18, 1925, one death, K. 1. du Pont dc Nemours & Co., accidents occurred, unskilled laborers were employed without skilled supervision, the arrangements for hand- I f ling the product were crude, the mixing and bottling were carried on under an ordinary laboratory hood, a n d / $ | although the men were given gloves and respirators,..... they had discarded them. At the time of their visit, however, an excellent building and equipment had been *`-$11 Catncy's Point, N. J. provided as well as working clothes, washing facilities,VJjffl Pcb. 38, 1925, one insane, Standard Oil Company, Bayway, etc., for the mem "Since the installation of the new '/If* N, J._________________ ._________________ ___________ _ filling and blending arrangement with the downward'; exhaust, no symptoms have been experienced by the 6, liver, /fi The mg.; distribution in one dog was: bone, 20Cf mg.; intestines lungs, 16 nig.; nn other organ hint so much as 10 96 mg. mg.;workmen, whereas previously complaint of sleepless- ' m VOM'MKfi4 IS'eviir-: 7.n n n ' h ' . i i r m j ' i l e a d - - H a m i l t o n h t Ai.. 483 ness. headache. loss of wrijehi rind appetite were quite sale of letr;!'ethyl lead and of ethyl gasoline wen* not common," suspended, hut were allowed to continue. The, Bureau Dr, Andrew McBride, commissioner of labor of she of Mimes began experiments in December, 1923, and state of New jersey, made ;m investigation of the just out1 year lates* made public a report on Exhaust Standard Oil plant and published {N o v , 25, 1921) a Gases from Jengines Using Ethyl Gasoline, The fact report in which he stated that he was opposed "to any that the report was issued by a government agency gave attempt to again produce this material by the same it an authority and an air of finality, as shown by the processing methods (hat were used in the past, as experi fact that: immediately after its publication the ban on ence has demonstrated that workmen can tint be safe the manufacture, distribution and sale of ethyl gasoline guarded against the effects of poisonous contacts," was lifted by the states of New York 8 and New Jersey, After the first death at Bayway, the other employees and also by recent articles from the pens of two public who had been exposed to tetra-ethvl lead were taken to officials.9 the Reconstruction Hospital for observation, Four died I f a few days later, several exhibited transient symptoms of mental disorder, and one was declared insane, Feb. JpY ^ 1925, The Standard Oil plant was closed after the I f f deaths of the four men in the hospital. The E. I. du Pont de Nemours & Co, plant at Carney's Point, N. J., where two deaths had previously occurred, was also investigated by Dr. McBride. His report stated that "the danger of exposure was reduced to a minimum/' but nevertheless, on Feb, 18, 1925, a man employed in this plant died from exposure to tetra-ethy! lead, 2, The Danger to Men Handling Ethyl Fluid.~r~Ethyl fluid is sold in one quart steel receptacles with pointed necks, sealed with soft tin caps. Tire service station REPORT OF T H E BUREAU OF M IN ES The experimenters used ordinary motor gasoline, to which was added 3 c.c. of tetra-cthy 1 lead and 2 c.c. of ethyl dibromid or trichlorethyiene, approximately 0.04 and 0.06 per cent., respectively, by volume. The appa ratus used was a 1,000 cubic foot air chamber through which air was driven at the rate of 30,000 cubic feet an hour, making a complete change every two minutes. The exhaust gases were generated by.a Delco engine and were delivered during the first period through 10 feet, of a 1*4 inch pipe; but since a great deal of the lead was deposited in this pipe, a change in the appara tus was made. April 5, and after that the gas .was sent in by a 30 inch straight: section of pipe and a muffler extending directly from th engine and discharging into o))erator who is to add ethyl fluid to the gasoline ill automobile tanks breaks the seal over an upright spike as he places the receptacle over the cup of the delivery tube of the gasoline tank. When the receptacle is empty, lie takes it oil and substitutes another. There is a recognized danger involved in this process, for the liquid may he splashed over the face and hands of the the chamber, while the gases were removed by a similar pipe ending near the floor level on the same side of the chamber. As a result, the quantity of lead delivered was increased from 0.5 gm. daily to 1.5 gm. The amount of lead, was regulated by the carbon monoxid content of the gas, which was always kept down to the "allowable" limit of 0.4 per thousand, established by eWii wor^er as he Jains the receptacle over the opening' Yandell Henderson and his colleagues as the highest spike. In view of this fact the manufacturers have permissible for the air in the New York-New Jersey Mi stated that in future, sales of tetra-etliyl lead will he vehicular tunnel. ]p& made only to refineries, where it will be mixed with The animals were placed in cages in the air chamber gasoline by specially trained employees and then distrib- for three and for six hours daily for varying periods. nted to service stations.7 This provision, however, is Twenty-three rabbits, fifteen guinea-pigs, four pigeons, ; purely voluntary on the part of the manufacturers, and eight dogs and two monkeys were used for the three ;m no state is it a regulation with the force of a law hour tests; an equal number.of rabbits and guinea-pigs, 'behind it. It is said that small stations which have three dogs and four pigeons were given six hour expo only one pump cannot buy ready mixed ethyl gasoline, sures, and at least half as many rabbits, guinea-pigs and !but must add the ethyl fluid to ordinary gasoline on pigeons were kept as .controls. All were quartered |I demand. together and given the same amount and kind of food 3. The Danger to Ftiling and Distributing Station at the same time. W Employees and to the Dubltc from Handling Ethyl After each running period the deposits in engine hood, Gasoline.--A study covering this problem is being con- exhaust pipe, drip pans and crank case were examinee! Inducted at present by the Laboratory of Industrial for lead, and it was found that about 63 per cent, of the | | Hygiene of the Columbia University College of Physi- lead in the gasoline was in these deposits, in the form.of * dans and Surgeons, New York, and as yet the data sulphate and chlorid or bromid, while the remainder ^collectecl are insufficient for the formation of a definite was discharged into the air of the chamber, the larger | statement. particles falling to the floor, the lighter remaining J 4, The Danger to Garage Employees and to the Public from Exhaust Gases from Engines Itsing Fdhyt tGasolinc.--The exhaust gases generated .by- the combus tion of ethyl gasoline contain lead compounds iti the form of more or less fine dust. The danger here would be from repeated small doses resulting in chronic lead jjpoisoning. The importance of this problem was rcalpfaed by the General Motors Research Corporation ; (later the General Motors Chemical Company), and suspended in the air, The carbon monoxid content of this air during the second period of the experiment averaged from 0.015 to 0.025 per cent,, and the lead, from 0.002 to 0.007 mg. per cubic foot. Of the animals, 50 per cent, of the rabbits, test and controls, died, and about 25 per cent, of the exposed guinea-pigs ; nine of the ten dogs survived, and also the two monkeys and the pigeons. All deaths are attributed to accident or disease, mostly of an infec J/dtc corporation requester! the United States Bureau of tious natur, No loss of weight was noted, no anemia, t) Hines to investigate the question. Pending the results no lead 'lines, no evidence of lead poisoning either "li&f this investigation, the manufacture, distribution and S. A t Albany, Jan, 20, 1925, on the advice of the Public Health Con noil of New York State. 7. Shrader, J. H .r Tctra-Ethyi Lead and the Public Health, Am. J. 9, Shrade r (Footnote 7): Sails, C. M.: The Nation's Health, New ib lU k . Health 1 5 : 313, 1925. York State Dept, of Labor 7 : !69 (Marc!) 35) 1925. MMt 7 h i /-'ri l i \ ! ! / . i/f / / / . I / / / / w, v /- / r i / . . J<hM`kavA.|6,M,19A25, i* ! If Htftg! 1 'i \ !II | >11HI )\ Ml fl u!M :i!i,d y T , " i I ! H- li< ,. 1\ ;Ifi I i ( ubn font, ;! imidifinn Hwnll-; with It, in a limited nalinM if! flic blond of s ix f in <:<: hour rabbits, four six- hcr of animals, has been demonstrated to be s a f e ." .ri honr r iililiiis and Iw o dogs showed no stippling o f fin; I o l.hrsc criiirisins we would add flic following: , ie<i cells, only ; l si it; hi p n ly ch ru in ain p h iliu , annslcvtosis and pnikiloryfn.sis, T in ' blood of the guinea pigs showed stip p lin g , but no m nre in the fcs! an im als than {`MANUK IN METHOD OF <`ONlit a`TtNO KXPERi- <g Mi-:NT AI END Oh' FIRST FOUR 'MONTHS 7 5n the out!nils. From the start of the experiment, Dec. 6, 1923, toy The carcasses of seven guinea-pips, one dog' and April 2, 1024, which covers, one half of the time of the?, eleven rabbits were examined fur lead by Fair hall's H) reported stiulv. the air delivered into the experimental7 method, and very insignificant amounts were found, the chamber contained an average of only 0.00043 mg. of- largest being 0,3d mg. per hundred grams of body lead per cubic foot (tests for lead averaged up to April;: weight. Lead was found in controls as well as in test 2), but for the last four months of the experiment they animals. The authors conclude, that this shows that lead in the air was increased to 0.0045 mg. per cubicL latent or delayed poisoning is not a possibility under fool (tests for lead averaged from April 2 to July 22),A these circumstances, since no storage of lead took place. Moreover, the ventilating system used during the firstfl To estimate the danger from the quantity of lead four months of study appeared to the investigators totf found in the exhaust gases, an experiment in inhalation he unsatisfactory, and on April 23 a change was madeAl and exhalation was made. Six men breathed these Under the new system the exhaust gases were conveyed gases through a specially designed mask with double to the chamber through a 10-inch pipe and removed-1'^ acting valves which collected the exhaled air. It was from the chamber by means of a similar pipe openingfv found that of the lead- inhaled, only from 8 to 27 near the floor level on the same side of the chamber.1 per cent, was retained, an average of 15 per cent. From this the authors reason that the quantities of lead found in the air of the test chamber arc negligible and that "th'c only danger of lead poisoning from products of combustion of ethyl gasoline seems lo be confined pos sibly to the mechanic who is continual!)' cleaning carbon from motors." This risk they believe to he no greater than that incurred by painters. Such an .arrangement might well produce a short- :4 circuiting of the air which would interfere seriously if with the general ventilation of the chamber. ^ Since two entirely different methods of ventilating the -f experimental chamber were used, it would appear thaD't the first four months of the experiment were of littleri value and that the results from the two methods should ri not he added together or averaged together. c a m c a l r e v i e w o r t i h ; nr. p o r t n v DRINKER AND EDS ALL A re.view of this report by Drinker and Fdsall 11 of Harvard lias appeared. These reviewers believe that flic report loses a truly convincing character because of j the small number of animals that actually went through the test. The mortality of both test and control animals was excessive (50 pet- cent, of rabbits, 25 per cent, of the guinea-pigs), and this lessens the value of the experiments. All these deaths arc taken as due to infections or accidents of various sorts, and are said to have been as frequent in control animals as in experi mental; but "it is unfortunate that better experimental stock was not available for'experiments of this degree of importance." They question the adequacy of the data on which the authors base their assertion that a man breathing the exhaust from an engine retains only 15 per cent, of the lead inhaled, and they arc unwilling to apply those results to animals without direct experi LENGTH OF EXPOSURE, OF ANIMALS A cursory reading of the report conveys the impres sion that some ninety-seven animals were exposed to the fumes from ethyl gasoline engines for a period last ing from December 6 to July 22, but ,a more careful study shows that, owing largely to the mortality among the animals, the actual period of exposure was much shorter. Blood pictures are given for only twelve of the test animals, and of these, nine were exposed for three months or less; viz., eight for'three months, one for two months, and three for five and a half months. Reports on tissues analyzed for lead arc given in only nineteen of ninety-seven exposed animals, and more than half of these (ten out of nineteen) were exposed to ethyl gasoline for only three months or less. Six fit animals were exposed for three weeks or less; four for from three weeks to three months ; six for from three to five months, and three for more than five months. ments oy tlie species in question. The material is, in CONTROL ANIMALS WERE NOT EXCUSED TO their view, presented in too insufficient detail. No data are given as to the size, composition or settling of lead in the air delivered to the test chamber, the lead being CARBON M ONOX ID The animals in the experiment chamber were exposed assumed to be in the form of particulate matter, not a to two poisons, carbon monoxid, and lead, the controls gas. Tt seems to them an unwarranted assertion that such particles-would pass out of, the air of a garage in to neither. Since it has been established by Nasmith * and Graham that exposure to small doses of carbon `>k the same manner as would the exhaust gases from gaso line engines. For this reason and because the amount monoxid for successive days produces in experimental animals an increased red blood cell count, some doubt Vs ik#-iv' of lead was kept extraordinarily low in the air of the must be cast, on the records of blood counts in the test test chamber, it cannot be assumed that these conditions animals. The tables show that there was no decrease imitated the actual circumstances under which the public in erythrocytes in the test animals, and the 'conclusion must meet the combustion products of ethyl gasoline. is drawn that these animals -showed no lead anemia. What the experiments do show is that "with a ventila To prove this point, the effect of repeated exposures tion system which delivered to the air prevents the atmospheric lead by engines using ethyl -gasoline to carbon animals. monoxid would As a matter of have fact, to be tested on control direct examination *of 1fis * from attaining more than 0,002 to 0,007 mg. of lead per J.10. Fair hall, L. T . : The Estimation of Minute Amounts of Lead in Biological .Material, Intiust. Hyg. 4 : 2 0 (M ay) 1922, 11. Drinker, C. K., and EHniil, D. L.: ,p tnriurt. Hyg. 7 : 94 (Fvb.) 1925. :smears did show some polychromatophilia, ansocytosis, and poikiloeytosis, all evidences of secondary anemia*, ,vy|- 12. Nasmith, G. G,, mul Graham, D Monos id Poisoning, j . Physio!, 7 ! 35. AfRd.V 7f^-- 'tjalology t.-neOgli. . of Carba rip Mt- tfvm.'1u* 840 I / :/ A'./A./ U Y L I I'.Ai) If . H! i LI ( )N f-.i AL. J-1H5 iO S 't H o h A N D *J LST A N ! MAI.S W E R E <J11A R'[ ER Ill J ' i n o F . 'l !/)./t The Bureau of Mines report states that '`all animals merequartered together and given the same amount jmd Mrs) t>f fond at the same feeding time.'' This procedure w open to criticism, since the excretions of animals exposed to lead would affect the control animals, and this may account for the fact that lead was found in the tissues of the control animals, for normal tissues should show no lead. For the same reason, the threehour animals should not have been quartered with the six-hour animals. CHARACTER OF DIET NOT STATED Xo statement is made regarding the food given the animals, and yet .diet and exposure to sunlight have a Erect influence on the fate of ingested lead and may fetermine whether it shall be stored in temporary harmJessness or circulated or excreted. If animals exposed to lead are put on a high calcium diet (milk) and placed m direct sunlight, they can accumulate large amounts of lead and show neither signs nor symptoms of lead poisoning. ANALYSTS OF EXCRETIONS Xo analyses of excretions were made, and yet exami nation of stools for lead gives important evidence'as to the amount of lend passing through the body. It would also have been important to know in which tissues the lead was found in the animats that were killed. This would have shown whether the lead was being stored in comparative safety in the skeleton or whether it was actually in circulation. INTERPRETATION OF SYMPTOMS IN ANIM ALS There is some confusion in the report with regard to the condition of the experimental animals. In the pro tocols, we find that one animal was emaciated before death and that one dog and one rabbit were paralyzed before death, but in the summary the statement is made that none of the animals lost weight or were paralyze!. This discrepancy between observations and conclusions is not explained. It is reported that none of the animals had colic, but colic is difficult to determine in animals and its absence can only be surmised. The statement is made with regard to a dog that was killed after paralysis had set in that "no stippling or lead line was found." Dogs poisoned by lead probably do not show stippled red cells.5'* The comment, "no lead line/' was made in regard to rabbits which died, but in rabbits lead poisoning is not accompanied by the forma tion of a lead line, which occurs in few animals, notably in cats, never in rabbits. Whether dogs poisoned with lead show a lead line is as yet not known. The cause of paralysis ami emaciation in the, experimental animals is not sufficiently explained, and with regard to the monkeys very few facts are given, no records of weight, blood findings, lead line or analysis of stool or urine. standard ns (hr "pr n in v ibb " or "ailowabb:" amount of carbon monoxid. in a personal communication, licn- dcTson makes this com m ent; 1! is indeed the highest amount that should, on ernunds of healtliftibiess, exist at any time in a ffarane; hnt there is ample evidence in .our 'investigations and, particularly, also, its the recent report by Dr, Etiore Ciampoiini of the New York Department of Labor, in his study of public garages, to show that the atmosphere in such places is often contaminated to a far greater extent than the 4 to 10,000. At present with the form of exhaust used on most automobiles it is quite impossible to keep the air of garages to a healthful standard in regard' to carbon monoxid. For the same reason, garage workers, even on the basis of the Bureau of Mines report, 'will be exposed to several times as much lead dust as were the animals reported in those experiments. Moreover, in the test room the rapid artificial ventilation prevented the lead from accumulating as dust as it does in a garage or on the streets, It would have been a nearer approach to real condi tions if the exhaust gas had been blown through the chamber for several weeks without putting any animals into the cham ber. Then, when an amount of dust had collected correspond ing to that which occurs in a garage, the exhaust could have been shut off, and the animals could then have been made to live in this dusty room for a few weeks. An experiment of that sort would have approximated real conditions in a garage. NEGATIVE RESULTS AS TO LEAD POISONING The period of exposure of the animals was too short and the method used was not such as to produce con vincing results. It is notoriously difficult to bring about lead poisoning in animals by the respiratory route unless an extraordinary measure is used, such as insufflation of lead dust, because the upper respiratory tract in these animals is very well protected. Such experiments can hardly be accepted as solving the problem for human beings. ' The conclusion drawn in the report that "the only danger of lead poisoning from products of combustion from ethyl gasoline seems to be confined possibly to the mechanic who is continually cleaning carbon from motors" is apparently based on the large proportion of lead which was deposited in the engine pipe, etc., and on the inhalation experiments, which showed that only 15 per cent, of the inhaled lead remains within the body. CONCLUSIONS We believe that these conclusions are not warranted and that the evidence so far available seems to show a real danger of chronic lead poisoning connected with garage work when ethyl gasoline is used and a possible Solubility in Grants per Liter of Water Lead, basic carljonntc (while l e a d ) ................................... 0.00(6 Lead oxids (red lead, litharge, e t c . ) .............................. 0,02 Lead sulphate .......................................................................... 0.041 Lead bremid ........................................................................ 8.3 Lead cfdorid ............................................................................. 9.6 QUANTITY OF E X H A U S T UAS IN TEST .ROOM NOT danger to the public from lead dust in the streets of TYPICAL OF ACTUAL CONDITIONS large cities, 'l'he compounds of lead formed by the The animals under test were kept in an atmosphere containing exhaust gases up to a concentration of 4 parts of carbon monoxid in 10;000. This limit was set because it is the amount of carbon monoxid set by Vandell Henderson and his associates as the highest limit to be allowed in the air in the New York-New Jersey vehicu lar tunnel. The investigators refer repeatedly to this13 combustion- of ethyl gasoline are the chlorid or bromid, according to the carrier used, and the sulphate. A quantitative analysis made by the Bureau of Mines' investigators of the deposits in engine head, exhaust pipe, crank case, and drip pan under the exhaust outlet, showed that 95.2 per cent, of the deposit consisted of lead, of which 40.1 per cent, was in the form of chlorid or bromid, and 55.1 per cent, in the form of sulphate 13. Aub, J, C ; Reznikofl, Paul; and Smith, D.>E.: ` Lead Studies, III, (p. 9 ). Now, the chlorid and bromid of lead are The Effect of Lead on Red Blood Cells, J. Exper. Med. 4 0 : 351 (Aug.) 1934. among the most .soluble of the lead salts, far more E ffo lU h '.l 7 / /) ' h 'n il) Tl'.T. i/Y )' OCl.li A, M. m "v iip, m $ 'y sniu hic in w ;ilc r llum ;it f ' llm sc ii s m ; i ily c n r u i i n l i red in 'I hB report of the Bme;ni of Mines ha In-fii critically *3 !iidtiM ry, ;r. crm he mtii by lhe ttrcunijMiiyjMg hib'lc " e.\ an iii led and found to In' iiudeqiml in scope, in The slairmcni, ilnncforc, iiiat only r5 per cent, of the (('clinic, and in condusiveness. It cannot be accepted as inhaled leaf! is relaimat is nnf entirely renssu.ring, rvi'ii (hr final word on the (lies! inn as p> the toxicity optf, if iue ,n eepfs if as piovcd, A finely divided soluble lead exhaust gases from ears using ethyl gasoline. The fttr-T eiimpound rail be readily absorbed from flic respirafory (her question, of the risk (o garage workers, is only I'1 tract, beginning with die nasal mucosa,1" and mav con lightly touched on in this report, and it also must await'-fe stitute a serious danger if administered in repeated a more thorough handling. $ doses, even if these are small. Because of the enormous and increasing use of It seems to us that the investigators have devoted )! .automobiles, the question of the danger to industrial (j their attention to the fine particles of lead suspended in workers and to the public which is involved in the pro-f; the air and have not attributed enough importance to dtiction and handling of tctra-cthyl lead and the use of the discharge of "large particles of scale which fall to ethyl gasoline is of the highest importance and calls for . the ground." and which, in garages, in taxi stands under a study which will be beyond criticism. Such an inves- f cover in the large railway stations, and even on the crowded streets of cities, might constitute a far from negligible danger. These particles will be ground fine by passing feet and swept up by currents of air, and when dissolved by rain and washed away, it is certainly possible that they may contaminate surface waters. It is also well to remember that when tetra-ethyl lead was first used in motor .gasoline, all the lead was deposited in the engine, and it was for this reason that a halogen carrier was added, in order to get some of the lead out ligation must include an intensive survey of a selected, group of individuals who have already been exposed:.1, to the gas, under known and varying calcium diet andqif varying exposure to sunlight, Their excreta should be,|T analyzed for lead. Only in this way can absorption of 41 lead and possible lead poisoning be ruled out. Perhaps |f of even-greater significance is the possibility that the./ gonads may be injured and posterity be affected,18 even ^ without any marked effect on the individual. This ;/ J ei the engine. Later improvements will probably result in further progress in this'direction and an increase in would necessitate studying the progeny of pedigreed f animals. Until investigations of this character have/ the amount of lead discharged into the an*. l( been made, it would seem to be in the interest of public/.?' health to suspend the use of tetra-ethyl lead in gasoline.st SUMMARY Telra-ethyl lead is added to gasoline together with a r volatile `'carrier,'' ethylene dihromid or trichlorethylene, to prevent "knocking" in motor engines. . PARATHYROID TETANY Experiments carried on by Eld ridge of the Chemical REPORT OF A SEVERE CASE TREATED W ITH Warfare Service show that tetra-ethyl lead passes MASSIVE DOSES OF . CALCIUM readily through the skin and that rapid acute poisoning LACTATE * may follow skin application or the inhalation of fumes. In animals so poisoned, the lead is found deposited chiefly in the skeleton. A cumulative effect also was C L A 1REJ, L. 'O GLE, M.D. BROOKLYN ..A51 noted, when animals were given repeated small doses by Almost since the beginning of thyroid surgery, a these two routes, death occurring in more than half. postoperative condiiion of tetany has been noted. This' The production of tetra-ethy! lead for commercial was at first ascribed to thyroid deficiency, but animal A purposes resulted in the poisoning of some sixty or experimentation clearly differentiated the process and seventy men and the death of ten men, in a period of proved it dependent on parathyroid deficiency, a fact t thirteen months, ending Nov. 1, 1924. Since then great subsequently substantiated clinically in numerous improvements in equipment have been made, and.only instances. two serious eases of poisoning have been reported dur The condition probably will increase rather than ing 1925. Ope man died, and one was declared insane decrease, owing, as one chief of a prominent clinic ,| in February, 1925. remarked, "to the necessity of removing more thyroid'/ The mixing of ethyl fluid with gasoline constitutes in order to secure a greater degree of cure." 1 a danger, the extent of which is as yet undetermined, to employees of refineries and service station employees. The use of gasoline to which ethyl fluid has been added constitutes a probable risk to garage workers and a possible risk to the public, of chronic lead poisoning, because the.combustion of tctra-cthyl gasoline results in the. formation of soluble compounds of lead, the chloric! and bromid fas well as the less soluble sulphate), which compounds pass out. with the exhaust gases in the form of light and heavy particles. The states of New York and New jersey prohibited for a time the use of ethyl gasoline, hut rescinded this order when a report was issued by the United States Bureau of Mines declaring that tests made on animals with exhaust gases from engines using ethyl gasoline had shown no evidence of plunibism in any of these animals. ( 14, Persona! communication lo tint authors from Prof, Julius SUegiUr., Department of Chemistry, University of Chicago, 15. Bltitngart, H. L.: The Absorption of Lead from the Nasal Mucosa, J, Indus*. ilyg. ii : tSJ (Sept.) 192.1. The treatment of this condition has always been a.y matter of grave concern. Parathyroid transplantation, ^ 'desiccated gland orally, extracts iff the gland subcuta neously and inf ravenously, and various salts by mouth, A by rectum and intravenously have been tried, but % usually without success in the severe cases. Erouin 2 was one of the first to call attention to the;/- oral efficacy of calcium and magnesium sabs in para-bit thyreidcctoinizcd dogs. Euckhardt and his co-workers8 y|L !6. (,'r>lc. L, I., ;fnd Rachhuber, L. j . : 'Che Effect of Lead on the (Irrm ('ells of the M a le Rabbit and Male Fowl as Indicated by Their Progeny, Vine, >Soc. Ex per, Rio!. & Med, 1 2 : 24, 1914, Weller, U, V.: The Rlastothoric Klicci of Chronic Lead Poisoning, j . M, Res,' ill !: 27!, UH5, " From the surgical service of Join: K, Jennings, (he Brooklyn 1Hospital. . Lahrv, F. B,: Parathyroi d Deficiency and Its Treatment, Boston M. X- S. 1 8 7 : I/O (A ug. 1 ) 1921. 2. J-Vnum: Com pi, rend. Acad, d, sc. 1 -t8 t 1922, 1909. 3. E u c kha rd t, A. R., and Rosenbloom, R. j . : The Prevention and Con frol of Para thyroid Tetany, P me. Soc, Ex per, Rio], & Med, 1 f>t 129, 1921. The Control and (Tire of Parathyroid Tetany in Norma! and. Pregnant. Animals. Science i> 0 : 4 8 , 1922. Luc.kbnrdg A. R., and Ilimnenstock, The Recurrence of Acute Parathyroid Tetany in Com*.: Sle.l'ely Parnthyroidrotomir.ed Animals During the Oestrus Cycle, Science 0 : 2 5 7 , 1912,.