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N36947 Ma x p h e d Bo w d i x c h DrrtKtiroK, Hk a i-t h a x d Sa ms t y Le a d In iu t s t r ik s As s o c ia t io n 420 Lk x j c n o t o n Av is . Ne w Yo r k 17.N.Y. DUP050314358 PROCEEDINGS of LEAD HYGIENE CONFERENCE Held at BISMARCK HOTEL CHICAGO, ILL. NOVEMBER 15-16, 1948 Price: $1.00 LEAD INDUSTRIES ASSOCIATION 420 LEXINGTON AVENUE NEW YORK 17, N. Y. DUP050314359 CONTENTS Page Opening Address Felix Edgar Wormser ............ ......................................................... 6 Solubility and Particle Size in Lead Poisoning Gordon C, Harrold, Ph.D., and Stuart F. Meek, M.D.................. Discussion, led by May R. Mayers, M.D......................................... 11 20 The Treatment of Lead Poisoning -- Past and Present David R. Johns, M.D. ...................................................... ............... Discussion, led by William C. Wilentz, M.D................................... 25 28 Preventive Medical Armor for the Lead Industry F. B-. Lanahan, M.D. ....................................................................... Discussion led by Elston L. Belknap, M.D..................................... 41 44 The Co-ordination of Industrial Medical Services Sherman S. Pinto, M.D......................................................... ........... 55 Medical Control of Lead Workers -- A State Viewpoint John E. Silson, M.D.......................................................................... Discussion, led by Warren A. Cook ............................................... 64 73 The Production Manager Looks at Industrial Health Fred M. Gillies ................................................................................... 78 The Effect of BAL on Experimental Lead Poisoning Harry Eagle, M.D. .............................................................................. 81 Discussion, led by Alsoph H. Corwin, M.D................................... 93 Air Pollution Regulations in Los Angeles County Louis C. McCabe, Ph.D...................................................................... 102 Discussion, led by William N. Witheridge..................................... 107 Aluminum and Silicosis John W. Berry, M.D............................................................................ Discussion, led by O. A. Sander, M.D.............................................. 112 118 Summation of Conference Proceedings Anthony J. Lanza, M.D........................................................................ 120 Round Table Discussion ............................................................................. 125 Urinary Porphyrins in Lead Poisoning Gordon C. Harrold, Ph.D................................................................. 129 v Discussion ............................................................................................. 134 Is 1 DUP050314360  . i': ...' ; LEAD INDUSTRIES ASSOCIATION LEAD HYGIENE CONFERENCE NOVEMBER 15-16, 1948 MONDAY MORNING SESSION November 15, 1948 Mr . Ro b er t L. Zie g f e l d [SecretaryTreasurer, Lead Industries Association]: Ladies and Gentlemen: I want to wel come you all here .on behalf of the Lead Industries Association. I am not going to waste any words because I know you want to get your teeth into the meat of this meeting. 1 hope that you will all enter into the discussions that are to fol low and that you will enjoy the social activities that have been arranged. The Lead Industries Association rec ognizes health as one of the most im portant problems the industry has. We have established a Division of Health and Safety for that reason. We hope to make that Division of the utmost service to the industry, to the medical profession and to the public. Now it is my pleasure to introduce the Chairman of this meeting who is well known to most of you, the director of Health and Safety of the Lead Industries Association, Mr. Manfred Bowditch. Mr . Ma n f r e d Bo w d it c h [Director of Health and Safety, Lead Industries Association]: My introductions of the speakers are going to be brief, because, obviously, you are here to hear the speakers, not to hear the introductions. The main prelude to our Conference will be by a man who was secretarytreasurer of the Lead Industries Associ ation from 1928 to 1947, and in my present position I very frankly marvel at the time, energy and knowledge that he was able to devote to matters of health and safety, in addition to his manifold duties as secretary-treasurer. He is now vice-president of the St. Joseph Lead Company and, very de servedly, president of the Lead Indus tries Association. Mr. Felix E. Wormser. DUP050314361 OPENING ADDRESS By FELIX EDGAR WORMSER President, Lead Industries AssociationPice President, St. Joseph Lead Company, New York, N. Y. It is my pleasant responsibility, and at the same time a rare privilege, to open this important Lead Hygiene Confer ence. My thoughts go back to 1937 when, here in Chicago, I had the honor of pre siding over a meeting of physicians rep resenting the member companies of the Lead Industries Association and some of their friends, to exchange experiences in the detection and treatment of lead cases. I am particularly delighted that so many of you who attended that meeting are again with us today, prepared to partici pate in this constructive conference. A great amount of water has gone over the dam, or should I say, has traveled through lead pipes, since 1937. This meeting will help to bring us up to date. Not being a medical man, and not wish ing to trespass on the time of the valuable papers which are to follow, I am going to make my comments as brief as pos sible. Perhaps the best contribution I can make to the discussion is to give you a little background. It has been my experience that many mistaken impressions about lead in hy gienic circles could have been easily avoided through better acquaintance with the lead industry. The United States is the world's greatest source of this in dispensable lead and uses large quanti ties of it each year. It would take 200 freight trains each 100 cars long to move the lead that is consumed in our country each year. A simple calculation will show that this amounts to about one million tons. In fact, consumption today is above this rate. It is about 1,200,000 tons a year. It' may be that the thought of this volume of lead being consumed an nually in the United States is petri- fying to those alarmists about the toxicity of our metal, as a million tons of lead, or two billion pounds, is a consumption of around 13 lb. per capita. On the contrary, my own in terpretation is that this record shows that, despite contact with lead in nearly all our daily activities, some of it remote to be sure, the absence of reported in jury on any other but an extremely modest scale, is one of the best evidences we have of the comparative safety to health under which lead can be produced and used today. Incidentally, you might be interested to know how such a vast amount of lead is obtained in the United States. Only about one-third of it is actually mined in the country. A roughly equal share is derived from the reclamation of junk or scrap which has assumed the proportions of a very important industry in the United States and which has become, parenthetically speaking, the largest lead mine in the world. The balance of our supply is imported from Mexico, Canada, Australia and other countries. Lead is becoming one of our most precious metals in point of price and available supply. You may have heard about this recently, and the fact that to day lead is selling close to the price of copper -- something unheard of, and which would have been considered fan tastic only a few years ago. Some of you serve mining companies, other smelting and refining companies, and some of you attend factories where pig lead is converted into white lead, cable sheathing, storage batteries, am munition, and dozens of other important lead articles. Today, lead assumes an even more important role in industry e DUP050314362 OPENING ADDRESS 7 than ever before, because we are on the threshold of great developments in the field of atomic power where lead will be protecting the lives of human beings from the effects of dangerous secondary radiation. I like to stress this point, be cause lead is so often condemned by virtue of its admittedly toxic properties, that it is refreshing to discover that it also has great value in the medical field as a preventive material, and by that I mean to prevent damage to the body from dangerous penetration of X-rays and other harmful electrical manifesta tions. Also, that its toxic quality is used to protect our food supply as an in gredient of insecticides. We can divide the use of lead into two groups, class (1) in the metallic form, such as pipes, sheets and alloys, and (2) in the chemical form as white lead, litharge, lead arsenate and red lead. The first or metallic class gives us little or no trouble from a health stand point, but the second may, largely be cause of the powdery nature of the product and the well-established fact that lead is ever so much more toxic when inhaled than when ingested. Al though we are concerned here largely with problems of industrial health, the question of public exposure is also part of the agenda, and I think that possibly some of my own experiences in this field may be worth while describing. When I first became seriously inter ested in the problem of lead hygiene quite a few years ago, I was inclined to accept without much questioning many of the pronouncements that were made about lead in hygienic and medical cir cles, but it soon became apparent to me that our knowledge was not as thorough as it .should be. Thanks to the perfectly enormous amount of work that has been done in medical circles over the past 35 years in more places than I can con veniently give credit to here, I feel that, like a good many fears that plague humanity, this one can be dissipated in the light of our growing knowledge. For example, during the war, in an effort to economize on scarce tin, all of which has to be imported into the United States, and to consume lead (which by the way becomes plentiful in wartime), I sug gested to an officer of the Food and Drug Administration that shaving cream might well be packed in lead instead of tin or aluminum collapsible tubes. He disagreed because he said, "Suppose someone shaved and cut his face? He would "be apt to contract lead poison ing." Comment is superfluous. Events subsequently made it necessary to use lead for the purpose and that it has been done with perfect safety I have no doubt. As a matter of fact, tooth paste was added to the list of products eligible for packaging in lead, and I am sure mil lions of people used it with complete safety. I must explain, however, that in all of these tubes an interior spray of a synthetic coating was used to protect the contents from any possible contamina tion by the lead. Here then was a large public experiment in the use of lead, where a hazard had been thought to ex ist, without any ill effects. Some years ago I had a visit from two eminent professors of agriculture from western colleges who had been delegated by the apple-growing industry in the northwest to investigate the spray residue problem. They told me that the apple industry was threatened with ex tinction unless something were done to establish a tolerance for lead which they could meet. I urged a complete and im partial investigation, and, because of the public interest involved, suggested the use of the U. S. Public Health Service. Most of you know that this was subse quently done and that the Public Health Service issued an excellent report, the conclusion of which was that they did 8 WORMSER not find a single case of lead poisoning where the exposure is most pronounced, among the 1,231 persons examined in do not contain any lead. the field, some subjected to high ex There is little excuse today for spe posure of the lead arsenate spray. cialists in the field sticking their necks Another example, in one mining state out with the assertion that orange juice it was alleged that water emptying into squeezed in an aluminum cup results in a beautiful lake used for drinking pur an attack of acute lead poisoning among poses, a lake 75 miles away from active children, and publishing the results of mining operations, had become so con the. investigation in a medical journal. taminated with lead picked up by the Nor should doctors rely exclusively water in a stream passing through mine upon the highly questionable evidence tailings or waste rock from the mines, of an X-ray bone examination to deter that die water was dangerous to drink. mine the presence or absence of lead When we made an investigation, we poisoning in children. found that the water samples from which Like my own field, engineering, the the lead determination had been made field of medicine has grown so vast that were merely gallon samples. Our pro it is beyond the bounds of human ac cedure, on the contrary, was to use complishment to be familiar with all its 1,000 gal. samples, analyzing the ample ramifications. Therefore, I recognize we residue obtained from evaporation. In have to he tolerant of those errors we no case were we able to check the ana detect in the medical field from time to lysts using the gallon quantities. I think time. Thanks in a large measure to the this shows the danger in using small excellent work of the American Medical quantities of water, or, for that matter, Association, through its Council on In any other material in detecting extreme dustrial Health as embodied in the Bos ly minute amounts of metal. ton Conference on Lead Poisoning two It has been interesting to me to see years ago, an important step forward other investigations of a public nature has been taken in clarifying a good also clear lead from undeserved criti many medical misconceptions about cism. For example, a survey made of lead. I hope that the American Medical the use of one drop of solder in sealing Association will carry on this good work evaporated milk cans, or the examina indefinitely. tion of the use of lead for weighting At the same time, I want to pay my silk. If we had time, I should like to respects to two publications of the tell you of our examination of numerous American Public Health Association cases of lead poisoning from white lead, under the auspices of its Committee on especially in infants, but I have already Lead Poisoning. These two books, prob expounded on that in a paper I pre ably well known, are: "Occupational sented before the American Medical Lead Exposure and Lead Poisoning," Association two years ago. It is here and, "Methods for Determining Lead in where anyone is apt to go astray on the Air and in Biological Materials," and easy assumption that because white lead should be in the library of any doctor is synonymous with fine paint, all paint serving the lead industry or at all in contains white lead. This is not so, as terested in the subject. It seems to me white lead has become a minority in also that ibis is a good time to pay volume of the various pigments used tribute to another agency which is sin for painting in the United States. Most gularly able to work in the field of in interior paints, and furniture paints. dustrial toxicology in a most construc- DUP050314364 OPENING ADDRESS 9 tive manner; namely, the U. S. Public Health Service. Particularly in the highly important field of analytical methods in diagnosis, the work of the U. S. Public Health Service has been outstanding. This is the very corner stone of medicine, for faulty diagnosis has lead to many misstatements in the field. Even prior to diagnosis is the' im portant question of verification of ex posure. In today's Conference we do not have to worry about proving ex posure, because we are dealing in areas where the greatest hazard exists; name ly, in the actual production and manu facture of lead or lead articles. We shall all, therefore, be interested in hearing of the progress that has been made in the diagnosis and treatment of lead poi soning. Although I realize that great progress has been made, I do not think industry will ever rest content until we reach perfection and that no one is hurt by the production or use of any lead product. In this battle the prevention of exposure is our principal weapon. That is also where great improvement has been registered. By keeping lead out of the atmosphere and by personal cleanliness, the lead hazard in manu facturing operations has been largely overcome, as you well know. This prog ress, I am confident, will be continued as more people realize that, not only from a humanitarian standpoint, but from a practical dollars and cents stand point, it pays to improve hygienic prac tices. In one of my numerous conferences with Dr. Aub, he once made an observa tion which I thought most helpful. It was that because of the widespread use of lead in industry, in so many different products, and in so many different plants, industry itself constituted a great laboratory from which, if proper rec ords were kept, the medical profession and government authorities could de rive a vast amount of data in the pub lic's and industry's interest. I subscribe to that opinion. One of the things we are doing here today is to develop an exchange of information from which certain conclusions can be drawn, and I am hopeful, as time goes on that the Lead Industries Association itself, under Mr. Bowditch's direction, will be able to develop surveys of great value to us all. For instance, I have always felt it extremely pertinent that in our own lead mines, and, so far as I know, in most lead mines, we have no trouble from the metal. The chief health hazard un derground is silicosis, but, no doubt, the precautions which are taken to lay silicious dust in metal mining operations also account for the excellent health record in lead. In addition, of course, there is the extremely high insolubility of galena, the lead sulphide. In a sim ilar manner, the experience of the prim ary lead smelters and secondary lead smelters, the experience of our white lead plants, storage battery industry and others, would be very useful. The late Dr.' Frederick Hoffman, as we know, endeavored to acquire a lot of useful information from an examina tion of a nationwide compilation of death certificates where lead was indi cated as a cause of death. This was an excellent project. Even though a lot of the certificates were of questionable statistical value, I would like to see more of this done. Indeed, the more I study our lead problems, the more I am con vinced that lead has nothing to fear from the truth, and nothing but the truth. So important has the subject of lead hygiene always appeared to the directors of the Lead Industries Association, that some time ago they authorized the ap pointment to its staff of a fulltime direc- DUP05031 10 WORMSER tor of health and safety, giving him ference, I want to express my deep carte blanche to operate in the field, thanks to you all for coming, and to with no reservation whatsoever. As a express my pleasure at being here where matter of fact, this was also the basis I can listen to you. on which I operated when I was active Now it is my pleasure to turn the ly engaged for the Association in doing meeting back to our Chairman. Mr. what I could to help improve hygienic Bowditch. conditions in our industry. My Board Ch a ir man Bo w d it c h : Our next never imposed any obstacle; their only speaker was for many years director of thought was to get at the scientific truth and to use it to the best advantage of the public which they serve. 1 am con fident that it will always be the policy of the lead industry, comprising as it the Industrial Hygiene Laboratories of the Chrysler Corporation in Detroit. Now, with Dr. Stuart F. Meek, who I am glad to say is also with us here, he does, mining, refining and manufactur is conducting the Industrial Health, Hy j ing, now I am happy to say, all over giene and Safety Service in Detroit. Dr. the world, and so in opening this Con Gordon C. Harrold. -! T 'i :!: t: i: DUP050314366 mm SOLUBILITY AND PARTICLE SIZE IN LEAD POISONING By GORDON G. HARROLD, Ph.D. crnd STUART F. MEEK, M.D. Industrial Health, Hygiene and Safety Service, Detroit, Mich. If I have been most impressed with the months, and to over 18 mg. PbCrO, per remarks that have been made. I was exposure day for from 12 to 15 months, probably more impressed with one of with no clinical or laboratory symptoms the earlier remarks, to the effect that of lead absorption. everyone wanted to get on with the meat From the above group, 26 men were of the meeting. Being part of that meat, selected on the basis of continuous ex I beseech your indulgence. For the more posure to the highest concentrations of carnivorous members, this work will be lead chromate. They had exposure days published under the auspices of myself averaging 6.2 mg. of lead chromate and Dr. Meek. for 27 additional months. The reports showed no laboratory or clinical results INTRODUCTION differing from the normal. In a previous study1, we provided evidence that lead chromate inhaled or ingested by human subjects did not exhibit clinical or laboratory findings indicative of lead absorption after ex posure to quantities of lead chromate greatly in excess of those regarded as safe for continuous exposure. That study involving two groups of 145 men and 40 men for 16 months was ex tended to 28 months for 20 men who were still exposed to high concentra tions based on an exposure day. We will, in this report, extend the observations to 40 months for 26 men, and in the second part of the paper, present data on men exposed to lead metal fumes. The information is evalu ated in terms of the solubility relations of lead salts in human lung fluids2 and in terms of particle sizes. This group of 26 men had exposure days of over 18.3 mg. lead chromate per day for 13 months, and to 6.2 mg. lead chromate per day for 27 additional months. The highest exposure day was 12.2 mg. and the lowest was 2.6 mg. in this 27-month period. The men on the job cooperated by wearing the test collecting devices. At the end of 40 months, the group basophilic aggregation was 0.7 and the lead-in-urine average 0.039 mg. per liter. Again, no clinical or laboratory results deviating from the normal were found. The above extension of the test results of the group, whose only selection was on a basis of continuous exposure to high quantities of lead chromate, indi cates that over long periods of time, such exposure does not cause demon strable ill effects. In view of Silverman and Drinker2 RELATIVE TOXICITY OF LEAD CHROMATE questions about physiological breathing rates, our last results for a period of 15 months with this group of 26 men Exposure io PbCrO* were derived mainly from the exposure days of the men on the job. All the In our previous report on the toxicity men cooperated to some extent, and no of lead chromate1, we evaluated the ac significant deviations were noted from tual exposure of two groups totalling those results which had previously been 185 men to amounts of lead in the form extended from a limited number of of lead chromate, never less than 4.0 men. These tests were not taken every mg. of PbCr04 per exposure day for 18 day, but some values were obtained IX DUP050314367 12 HARROLD- MEEK every two weeks from different indivi men had worked for over 15 months duals. The individual differences which reported lead-in-air values of 74, 105, did appear were not important to the 118 and 121 mg. of lead per ten cubic general average over a long period of meters of air using the electrical pre time. The actual exposure time of no cipitator as the collecting instrument. worker was reduced for more than two Since such methods of standards re weeks over the total exposure lime by porting, based on the air content of con the wearing of test equipment. taminant per ten cubic meters of air, Efficiency of Packed Tube Collector are commonly employed, it can be seen that some explanation is required as it The efficiency of the "packed tube col is determinable that lead absorption of lector1" was checked at 28 and 40 liters lead compounds such as lead oxide, airflow per minute using an electrical when reported in much smaller concen precipitator in a series. Three determi trations, have caused lead absorption. nations averaged 99.7 percent relative Thus, our correlations4 between lead- efficiency at 28 liters per minute, and in-urine and basophilic aggregation were three determinations at 40 liters airflow good when lead oxide was involved. averaged 99.8 percent relative efficiency. Furthermore, our first lead chromate The lead test material was sprayed lead report1 cites the excellent agreement chromate in concentrations of 120 to 150 between basophilic aggregation, lead-in- milligrams of lead chromate per ten urine, and lead content of the air when cubic meters of air as determined by the lead oxide is involved. We have addi electrical precipitator. tional information supporting this point. Air Lead Concentrations Two hundred and one (201) men ex posed to concentrations of lead-in-air Per Ten Cubic Meters averaging 1.24 mg. of lead per ten cubic However, the concentrations that this meters had a basophilic aggregation group of 26 men were exposed to based average of 0.9, and the lead-in-urine on the amounts of lead chromate per average was 0.081 mg. per liter of urine. ten cubic meters of air using the elec Other investigators5, B have somewhat trical precipitator and the midget im- similar data which refer in the main to pinger as sampling equipment were the soluble lead compounds--compounds much higher. The averages comprise readily soluble in body fluids. 328 individual air tests for the first We have found that when lead chrom 13-month period, and 628 separate air determinations for the 27-month period. For 13 months, the exposure average ate1 was involved, this correlation was not evident. There is a correlation be tween the basophilic aggregation and the was 117.1 mg. of lead chromate for ten lead-in-urine, but none with the amounts cubic meters of air. For the following of lead-in-air. 27 months, the average was 41.3 mg. of lead chromate per ten cubic meters of HYPOTHESIS air. The lowest values found in one area Our work2 on the solubility of lead where two of the men were working salts in human pleural fluid shows that averaged 12.1 mg. of lead chromate per lead oxide and lead carbonate are much ten cubic meters of air for the last six more readily soluble in human lung months' exposure period. fluid than lead chromate and lead ti- An outside agency checking one of tanate. This fact, when isolated from the work places where some of these 26 the actual concentrations, is only im- DUP050314368 SOLUBILITY AND PARTICLE SIZE 13 portant in that it allows a prediction that the more soluble salt will probably cause signs of lead absorption to appear more rapidly than in the case of the less soluble salts. However, we believe the quantitative evaluation of the amounts of impure lead chromate in human pleural fluid2, indicates a possible explanation of the lack of harm due to very large quanti ties of inhaled lead chromate. It has been suggested that the synthetic coat ing on the lead chromate paint would prevent the dissolving of the lead com pound in the human organism, but this is not a noticeable deterrent to lead intoxication when paints containing lead oxide, lead sulphate, or even lead carbonate are sprayed. Furthermore, we did not use a coated lead chromate in our solubility deter mination. These quantities had not been re ported in the literature for the solubility of the lead oxide, lead carbonate, lead chromate, and lead titanate in human pleural flqid or blood serum prior to our recent paper2. We are now suggest ing a possible explanation which has been offered freely in the past based on generalized information or belief. We now have scientific data to substan tiate these beliefs. We propose an explanation based on the extremely low solubility of lead chromate in human pleural fluid and blood serum. The amounts found solu ble in one liter of these fluids range from 1.28 mg. PbCr04 in pleural fluid to 1.14 mg. PbCrO, in blood serum. Since the total amounts of tissue fluid which could act as an exchange medium between the lung and the blood are limited, a saturation of this limited quan tity of fluid would provide total quanti ties of lead ion less than 1.0 mg. This quantity of lead is subject to a contin uous unbalanced equilibrium with the blood, and finally with the kidney and the excretory product, the urine. The maintenance of saturation of these fluids would require, according to the laws of mass action, very large quantities of the less soluble lead chromate in the lung. When it is considered that usually, but not always, no clinical symptoms are observed when 0.2 to 0.3 mg. of lead are found in a liter of the urine and amounts of 0.05 to 0.1 mg. of lead per 100 grams of whole blood, the possibili ties of getting even 0.5 mg. of lead in the body fluids from a quantity of lead chromate of 1.0 mg. per liter of body fluid concentration is remote in even exceptional industrial exposures. This information may appear more significant if we point out that 0.05 mg. to 0.1 mg. of lead per 100 grams of whole blood is close to 0.5 to 1.0 mg. of lead per liter of blood. We, therefore, are comparing 0.2 to 0.3 mg. lead in the excretory product, the urine, to 0.5 to 1.0 mg. of blood lead in the same vol umes of fluids to a compound which dissolves in blood serum in the range of 1.14 mg. per liter. Actually, our measurements of 26 men exposed to. at least 6.2 mg. of lead chromate for over 40 months, and for a large portion of the time to from 15 to 20 mg. per day, showed that this saturation was not only not reached, but that the lead-in-urine and basophilic aggregation dropped to normal during a period of time when the exposure day indicated an inhalation of 6.2 mg. of lead chromate. Furthermore, for 13 months of exposure to over 18 mg. of lead chromate, no significant deviations were noted from the results observed at the end of one month's exposure. Based on these observations, we sug gest that the insoluble lead salts which prove to have solubilities in the range of 1 mg. or less in human lung fluid at about 37C. will not be likely to be DUP050314369 14 HARROLD-MEEK causative of lead intoxication from in halation in quantities of less than 20 mg. of insoluble lead compound per ten cubic meters of air. We do not propose this as a standard of the M.A.C. variety, but we do suggest that it is a fact based on scientific observation. It is our observation that even this figure may be extended considerably if more insoluble lead salts are considered. Thus, with purified lead titanate where the solubility is about 0.28 mg. PbTiCfi per liter of blood serum, we may be approaching a range where a true equi librium exists between the amounts of lead absorbable through inhalation and the amounts excreted without harm to the human organism. This relation would not obtain with impure lead ti tanate containing lead salts readily solu ble in body fluids. It is believed that any lead intoxications which may occur in a lead salt of this level of solubility would be due to the admixture, or for mation, of a more soluble lead com pound. SOLUBILITY, PARTICLE SIZE AND EXCRETORY RATES Our study of workers exposed to lead chromate1 has led to the question as to whether or not somewhat higher levels of urinary excretion than that of the general population can be maintained without the demonstration of clinical symptoms. In the cases of over 100 men exposed to large quantities of lead chromate, the urinary lead excretory rate rose to 0.1 mg. per liter of urine and remained above 0.06 mg. per liter of urine for 18 months with no demonstrable damage. Certainly there must be some regulatory mechanism to adapt the organism to changed conditions. In a previous study4, we were able to show that the average individual in an industrial en vironment, exposed to more lead than the normal population, did have a some what higher lead excretory rate of 0.05 mg. per liter of urine than had been reported for the general population7. This indication has been supported by Dreessen8 in his study on lead storage battery workers not exposed industrially to lead, whose urine contained 0.06 mg. of lead per liter. That this rate is in equilibrium with the exposure is shown by the return to completely normal industrial levels, both for lead-in-urine and for basophilic ag gregation test, even though exposed to over 6.0 mg. of lead chromate when in the air of the work place, and over a longer period of time, approaches the normal values given for the general population. While we have, until this point, been concerned with the solubility of lead salts as related to the environment and the effects on humans, we wish also to discuss the effects of particle size on solubility, rate of absorption, and rate of excretion. In the case of the melting of lead compounds and alloys, it has been re ported9 in connection with brass found ries that there is not too much appre hension in this group concerning lead intoxication. This has also been our experience and that of others. It has also been reported that the correlation of lead-in-air, lead-in-urine, and blood stippling is not good. Stalker9 reports his findings that where the at mospheric lead is in three out of four foundries, below 1.5 mg. per ten cubic meters of air, the urinary lead was ex cessive for 34 percent of the workers. They also noted other work where urinary lead of from 0.18 to 0.21 mg. per liter with air concentrations ranging from 0.29 mg. per ten cubic meters to 11.8 mg,, and under winter conditions, 38.5 mg. in pouring areas. Finally, it was noted that only 31 DUP050314370 SOLUBILITY AND PARTICLE SIZE 15 percent of the eases having high urinary value was 43.6 mg. The lead-in-air lead (over 0.15 mg. per ten cubic me concentration shown in column 1, Table ters) and 42 of the workers with high I, representing conditions two years blood lead (over 0.07 mg. per 100 earlier averaged 24.6 mg. of lead per grams) had high stippling (over 1,800 ten cubic meters of air. per million). While in general agree The lead-in-air average in the pouring ment with the doubts generally ex area of 23 samples was 16.4 mg. The pressed about the non-specificity of stip lowest value was 8.1 mg., and the high pled erytherocytes for specific and sin est was 21.2 mg. gle cases, we think it interesting to note The particle sizes involved ranged the above small percentages of high from 0.1 [i or less to 1.0 ix for 98 percent stippling values when most of the evi of the particles with over 90 percent of dence submitted tends to the belief that the particles less than 0.5 . greater percentages of high stippling The urinary lead average for 20 ex would occur due to the fact that these posed individuals in the melting areas cells appear from many other sources. was 0.445 mg. per liter, and the average Sanders10 has shown that stippled ery reported two years previously was 0.46 therocytes are not too reliable in single mg. per liter. cases, and should be viewed with caution The urinary lead average for 13 ex in group studies. posed individuals in the pouring area We4 have shown in a limited number was 0.31 mg. per liter. of old lead cases that the basophilic Table I shows the variations existing aggregation did not truly reflect those in individual samples, as well as the conditions presumably existent in the fact that the average some two years men concerned. later was slightly lower than the first Finally, Stalker's8 report states that samples of urine. In the composite a group with the highest urinary lead- melting area exposures, some of the in-urine values did not significantly vary samples of urine in the second column from a general group of foundry work were checked by a polarographic meth ers as regards the physical signs of lead od and good checks were obtained. poisoning displayed on medical exami These results are considerably higher nation. than the other reports we have seen, We have recorded studies on 33 men and yet in no instance, to our knowledge, exposed to brass fumes. These are pre have the men made complaints, or been sented because they' add some data re away from work. It is realized that lating to the problem of lead poisoning these cases represent too few to gene in relation to soluble lead oxide in the ralize from, but in conjunction with finely divided state and in somewhat other reports in the literature, it brings greater exposures than usually reported up one fact and that is that much higher in the literature. lead-in-urine values seem to persist Twenty-eight air samples were collec when the lead is: (1) soluble in body ted by the electrical precipitator and fluids, (2) small in particle size. analyzed by the dithizone method re As our lead chromate exposures indi ported by Harrold, Meek and Holden11. cate that there is a considerable varia The lead-in-air average was 30.2 mg. of tion in the amounts of lead-in-urine com lead per 10 cubic meters of air in the pared to the clinical symptoms and the melting area. No values of less than lead in the form of insoluble lead com 19.7 mg. were found, and the highest pounds in air, there is also some varia- i DUP050314371 16 HARROLD - MEEK Table I Melting Area Pouring Area Initial Tests Average lead-in-air 24.6 mg. per 10 cubic meters. Number of Men Ex posed -- 20 Cheeks two years later Average of 28 samples 30.2 mg. of lead per 10 cubic meters of air; High value 43.6 mg. lead per 10 cubic meters of air; low value 19.7 mg. lead per 10 cubic meters of air. Urinary Lead in mg. per liter 1.01 0.06 0.57 1.04 0.41 0.59 0.68 0.95 0.74 0.21 0.58 0.34 0.04 0.49 0.15 0.48 0.14 0.05 0.60 0.15 Urinary Lead in mg. per liter 0.74 0.10 0.68 0.44 0.51 0.47 0.60 0.33 0.58 0.34 0.61 0.42 0.08 0.48 0.40 0.58 0.15 0.41 0.76 0.21 Ave. 0.46 mg. lead per Titer of urine Ave. 0.445 mg. lead per liter of urine tion between the lead-in-urine and leadin-air when the special cases arise of finely divided lead oxide which is very soluble in body fluids. Hypothetically, it may be that such circumstances may lead to a more rapid transport of the lead into the urine with its removal consequently unbalancing the equilibrium between the lead in the lung and tissue fluids and the blood so that this lead is excreted in larger quan tities than are considered normal based on our usual experience. Of course. Average of 23 samples,. 16.4 mg. lead per 10 cubic meters of air. High value, 21.2 mg. lead per 10 cubic meters of air. Low value 8.1 mg. lead per 10 cubic meters of air. Number of men exposed -- 13. Urinary Lead in mg. per liter 0.21 0.44 0.47 0.36 0.38 0.51 0.22 0.16 0.14 0.17 0.48 0.14 0.34 Ave. 0.31 mg. lead per liter of urine small particle size carries other conno tations which will be discussed later. There are other unpublished instances involving several hundred men where the lead-in-urine has been higher than we have reported without public or private reports of outbreaks of lead in toxication. Elkins14 has pointed out the lack of appreciation for urine test data among industrial hygienists. We would like to caution against the setting of fixed and arbitrary lead-in-urine values because of the apparent variability of this factor as influenced by the chemi cal and physical characteristics of the lead compound involved. This point of view has been well stated in Hamlin and Weber's15 study in the brass foundry industry where they found that lead intoxication rarely occurred unless the rate of excretion was over 0.3 mg. lead per liter of urine and that values up to 0.2 mg. lead per liter of urine did not have definite signifi cance. They state that marked correla- DUP05031 SOLUBILITY AND PARTICLE SIZE 17 Table II Table 111 Lead Soldering Fumes Lead Melting Pb in air Pb in urine 'Number of mg. per 10 mg. per Basophilic Persons cubic meters liter Aggregation ExposedAverage Average percent 29 Less than 0.5 0.12 63 " 1,0 0.14 67 77 tion exists between the lead intoxication, lead-in-air and in urine. T'he disagree ment of Stalker in his study of Kentucky foundries is partly attributable to the very low range of lead-in-air reported. Our experience with larger lead-in-air exposures duplicates Hamlin and Web er's experience, but considering the mat ter- of fine fume coupled with the great solubility in human body fluid of the lead oxide involved, the appearance of high lead-in-urine values, from very small amounts of lead-in-air, is expec table. Our available evidence does not indicate serious lead intoxication from other lead-in-air exposures in lead smelt ing operations, or operations where only heated lead is involved in moderate con centration. In the lead soldering fume work shown in Table II, the air test average represents samples taken every two months for five years. Some of the leadin-urine data are represented by persons exposed four years and some five years. Each average is composed of lead-in urines determined at three to four month intervals on all the exposed personnel and the basophilic aggregations were taken at the same lime. In the lead melting operations. Table III, air tests were taken ever)' three to four months. Lead-in-urine and baso philic aggregation were taken every four to six months for eight years. The tests in this table were selected from several thousand on the sole basis of having data available for a reason ably long period of time from various Pb in air Pb in urine Number of mg. per 10 mg. per Basophilic Persons cubic meters liter Aggregation Exposed Average Average percent 11 Less than 1.0 6 " 1.0 4 " 0.5 0.18 0.22 0.16 86 81 72 molten lead operations.The operations involved had a low percentage of labor turnover. That data would agree with the view that there is no correlation with lead-in-urine and lead-in-air values though none of the various physicians who examined the men ever found any clinical symptoms, nor do we have any record of sickness in these people which would suggest lead poisoning. SUMMARY AND CONCLUSIONS Our experience with large numbers of lead-in-urine values correlated with basophilic aggregation percentages and lead-in-air concentrations leads us to accept a variable lead-in-urine value, a variable lead-in-air, and a variable baso philic aggregation, depending entirely on the lead compound and state of sub division involved. Hamlin and Weber's15 experience in a brass foundry' is cor roborated for brass foundries, and per haps for all very finely divided lead oxide and lead vapor exposures. It may not completely represent the case even in some types of lead solder ing because of the coarser lead oxide dross which is sometimes an important factor. The same situations do not appear when very insoluable lead compounds, in any state of subdivision, are being considered. It may not follow, nor should we be construed as believing, that lead fume does not cause lead poisoning. It can DUP050314373 18 HARROLD - MEEK and it does, but we are pointing out that it is entirely probable that larger amounts of lead-in-urine may be found when finely divided, soluble lead com pounds are involved than are usually accepted as standards, and rightfully so for the usual exposures to lead com pounds readily soluble in body fluids. We, likewise, do not conclude that lead chromate cannot cause lead poison ing under certain conditions, but the evidence we have presented makes the appearance of lead intoxication from this source highly improbable in the industrial exposures which are likely to be encountered. This conclusion is based almost entirely on the solubility charac teristics of this compound. In those instances where the amounts of lead compounds which can be dissolved in body fluids, are equal to, or less than, the amounts which are transported and eliminated without harm to the organ ism, the potential saturation limit is the important factor. The factor of solu bility, in this instance, is independent of particle size and, perhaps, of other pos sible influencing factors, whereas lead compounds soluble to a great degree in body fluids are dependent on particle size, both in regard to the rate of solution and other factors such as the transport of extremely fine particles in protecting envelopes. The question of particle size in dust exposures, principally relating to silica, has been re-evaluated recently.121 3 In particular, Landahl and Herr mann13 have indicated that from 20 per cent to 35 percent of the particles in the size range from 1.0 ,u to less than 0.1 p are retained in the lung, and further reduction in size indicates increasing retention. They further show that in creasing the inspiratory flow increases the efficiency of lung retention of small particles below 1.0 micron as does in creasing the tidal air at a constant in spiratory flow rate. These factors are related to the more energy-consuming tasks in foundry work. The increase in dissolved lead of small particle size (less than 0.5 ft) is, moreover, markedly increased due to the much larger surface area involved. We believe that this factor, coupled with the high concentrations of lead oxide found per unit volume of pleural fluid, markedly increases the rate of solubility in the body fluids, and that this lead is then transported and ex creted at higher levels than would be the case with the slowly soluble, larger size particles. Within certain limits typi fied by 1.0 mg. lead per liter of blood and 0.3 mg. lead per liter of urine, this lead will usually cause no harm, where as it is more likely that larger sized particles in those concentration levels will cause damage. This concept is, of course, still dependent on the total dos age of lead available to cause damage, as is usually the case. However, with a rapid transport rate in the body fluids, the non-exposure periods away from the work environment provide an in creased opportunity to keep a lead level which will not become critical, whereas for the soluble, but larger sized lead oxide particles, an accumulation of the working day will not be so readily dissi pated. The limiting value in the case of less soluble lead compounds is, then, the solubility in body fluids which does not exceed a certain excretion rate which is readily maintained without noticeable harm. The mechanism of transport of ex tremely finely-divided lead is not clear. The. work of Aub16 and Brooks17 has been challenged by Kehoe.1,s It is pos sible that when the lung receives parti cles of less than 0.1 micron, a process akin to gaseous diffusion may result and that a film may permit the transport of i SOLUBILITY AND PARTICLE SIZE 19 the lead particles in the blood stream relatively unchanged. It is speculatively possible that the removal from the lung of the dust particles by dust cells or phagocytes may be accomplished with out preliminary dissolving. While it is true that colloidal lead compounds may form other chemical compounds and act as soluble lead salts in the blood stream as described by Kehoe18 it is, never theless, not proved that the very finely divided lead dusts which we are talking about act as colloidal lead under the experimental methods of intravenous administration employed in these stu dies. The instances of increased urinary lead in humans referred to in this paper may be confirmation of transportation, protected in some unknown manner, without chemical transformation or change. Whether this be true or not, Kehoe18 has stated "There is an equi librium established with an environment in which lead absorption was unavoid able," and "that the presence of larger amounts of lead in the excreta long after experimental administration should not be interpreted as evidence of reten tion by the tissues." Our conclusion is that somewhat larger than usual lead-in-urine values may appear when the exposure to at mospheric lead is in the form of finely divided particles, and that the appear ance of larger amounts of lead-in-urine in these situations may not be indicative of actually, or even potentially, harmful atmospheric exposure. BIBLIOGRAPHY 1 Harrold, G. C., Meek, S. F,, Collins, G. R., and Markell, T. F., "Toxicity of Lead Chro mate," /. Ini. Hyg. & Tox., 26, 47, (1944). -Havrold, G. C., "Solubility of Lead Salts in Human Pleural Fluid and Blood Serum," (To be published). sSilverman, L. and Drinker, P., "Use of the Exposed Worker as an Air Sampling Unit for Contaminants," J. Ind. Hyg. & Tox., 27, 22, (1945). *Meek, S. F,, Collins, G. R., and Harrold, G. C-, "Correlation Coefficient Between Baso philic Aggregation Test and Lead-In-Urine," J. Ind. Hyg. & Tox., 22, 401, (1940). 'Elkins, H. B., Ege, S. F,, and Ruotolo, B. P., "Evaluation of Lead Hazard," J. Ind. Hyg. & Tox., 23, 256, (1941). Smucker, C. H., and Kistler, J. B., "The Evaluation of the Lead Hazard in the Decorat ing Department of a Glass Plant," J. Ind. Hyg. & Tox., 24, 1, (1942). 7Kehoe, R. A., Thamann, F., and Cholak, J., "Normal Absorption and Excretion of Lead," J.A.M.A., 104, 90-92, (1935). 8Dreessen, W. C-, "Health of Lead Exposed Storage Batter)' Workers," J. Ind. Hyg. & Tox., 25, 67, (1943). 9Stalker, W. M., "Lead Exposure in Brass Foundries," J. Ind. Hyg. & Tox., 29, 94, (1947). 10Sanders, D. W., "Measurement of Indus trial Lead Exposure by Determination of Stip pling of the Erytherocytes," J. Ind. Hyg. & Tox., 25, 38, (1943). 1 -Harrold, G. C., Meek, S. F-, and Holden, F. R., "A Practical Method for the Rapid De termination of Lead When Found in the At mosphere," }. Ind. Hyg. & Tox., 18, 724, (1936). 12Hatch, T,, and Hemeon, W. C. L,, "Par ticle Size in Dust Exposures," 3. Ind. Hyg. & Tox., 30, 172, (1948). 13Landahl, H. D., and Herrmann, P. G., "On the Retention of Air-Borne Particulates in the Human Lung," J. Ind. Hyg. & Tox., 30, 181, (1948). 14 Elkins, H. B., "Urinary Excretion of Industrial Poisons," Ind. Hyg. Nevis Letter U.S.P.H.S., Vol. 8, No. 10, page 14, (1948). 15Hamlin, L. E., and Weber, H. S., "Control of Lead Hazard in Brass Foundry Industry," 1. Ind. Hyg. & Tox., 29, 367-377, (1947). 16Aub., J. C., et al; "Lead Poisoning," Med. Monographs 7. p. 24, (1926). Wms. & Wilkins. 17Brook, John, "The Interaction of a Finely Divided Lead Suspension With Blood Serum, Ringer Solutions, and Aqueous Phosphate Solution," Bio. Che. ]. 21, 766, (1927). lsKelioe, R. A., Thamann, F., "The Be havior of Lead in the Animal Organism--III Colloidal Lead Compounds," /. Lab. & Clin. Med., Vol. XIX, No. 2, 178, (1933). DUP050314375 2D DISCUSSION Ch a ir ma n Bo w d it c h : We have now reached our first discussion period. Dr. Joseph Aub was to have led the dis cussion of Dr. Harrold's paper. When I saw Dr. Aub in Boston last Thursday, I found him greatly overworked and not feeling too well and I did not have the heart to try to pressure him into keeping this engagement, sensing that he really felt that he should not. I thereupon sent an S.O.S. to another lead authority and friend, this one in New York, and it was characteristic of her that she wired me here in Chicago to say that she would be happy to under take this assignment, adding that she would arrive in Chicago yesterday, and if there were any further matters in con nection with the conference in which she could help, she would be only too glad to do so. She is an authority, widely read and quoted, on almost all subjects of indus trial hygiene, and is a member of the Committee on Lead Poisoning of the American Public Health Association. She has been associated with the Divi sion of Industrial Hygiene of the New York Labor Department since 1923, and has been its assistant director and chief of the Medical Unit since 1937. Dr. May R. Mayers. DISCUSSION Dr . Ma y R. May er s [New York State small for the support of a thesis of such Department of Labor, New York, N. Y.]: importance. I think it is very sugges Mr. Bowditch seems to have these dates tive. I am sure Dr. Harrold must feel very much more clearly in mind than as I do, that there are a lot of questions I have, and I am really surprised to which have arisen in connection with find that one can play around with this piece of work on which he would industrial hygiene for that many years like further data, just as I would. No Ji and still get a lot of fun out of it I doubt he will some day be able to pre guess it is an interesting reflection on sent it to us. the field. It would be very interesting, for exam I am sorry Dr. Aub is not able to be ple, to learn, with reference to a less here this morning to discuss Dr. Har soluble lead compound such as lead rold's paper. I would, myself, be great chromate which, presumably, is ab ly interested to get his personal reactions sorbed into the blood stream slowly, to it. It is a very interesting paper. As and is present there in relatively low it is, I would say that, perhaps, I am concentrations, whether the excretion of more sorry than you are that I have that material will continue for a much had to pick up this assignment at the longer period of time than is the case last minute. But I am very glad to give with a soluble lead oxide which goes you my thoughts on it. in and out, perhaps, more rapidly. I Dr. Harrold has presented a very in think that would be quite interesting teresting thesis in connection with the to know. matter of solubility and particle size as On the other hand, I feel that we it influences the excretion of lead in the ought to know, before drawing too urine, and lead intoxication; and he has many conclusions, a lot more about the presented some very interesting data actual stages of absorption and trans with reference to it. portation of the lead chromate in the Perhaps my first feeling about the body. There is quite a jump in the data is that the numbers are a little bit paper, I think, between lead in the air i! DUP050314376 SOLUBILITY AND PARTICLE SiZE 21 and lead in the urine. Lead appears in large (and that is true not only of lead the blood; some of it is stored before but it is true of many other substances it appears in the urine. as well) in an individual worker there Dr. Harrold apparently has not been is not necessarily any correlation be able, as yet, to provide us with neces tween signs of intoxication and his ex sary data in the various situations he cretion in the urine, of that substance. discusses, with which to more closely On the contrary, it has been very strik correlate lead in the air with lead in the ing that, where there is very little ex whole blood and with lead in the urine. cretion, we have frequently found signs I think that one must get much more of intoxication; and where there has detailed information with reference to been a great deal of the substance ex the in-between stages before one can be creted, there has in many cases been entirely satisfied to draw too final con complete absence of intoxication. That clusions on just what has happened; is something that I think one must never why this lead appears in the urine in forget. the way that it does, under those differ In dealing statistically with this ma ent circumstances. terial, therefore, it is very important I think that physicians are quite pre not to overlook these facts, and to make pared to accept, though' we do it a proper allowance for them. little bit reluctantly, the fact that there The other point I would like to men has been demonstrated a very practical tion is the use of basophilic aggregation usefulness in getting group urine sam in such a survey. It has its uses. How ples for purposes of industrial control. ever, I feel that, when one is working I think we are very anxious, however, out refinements, in terms of certain that that not be confused with the prob special chemical and physical properties, lems of protecting individual workers such as solubility and particle size, in who vary greatly in their susceptibility. trying to differentiate between very If one were to have astronomical num closely allied chemical substances, one bers one could statistically, no doubt, must go further than merely investigat iron out very satisfactorily all sorts of ing a single element, such as basophilic variables, including variables in indivi aggregation and correlating that one dual susceptibility. Within a small group element with all of these other factors however and in the average practical in a complex picture. situation in a plant, trying to protect First of all, basophilic aggregation, the health of its workers, I feel that stippling, or any other single feature whatever usefulness there is--and there merely represent special aspects of a is a great deal of practical usefulness blood dyscrasia which is caused by lead. in this group urinalysis for purposes of They are only elements in a very com control -- it must always be supple plex hematological picture. 1 will not mented with a great deal of attention to go into that; I do not want to take too the individual worker's health and his long on this discussion. But the point physical condition. Complete evidence is, I do not see that there is much value of what is going on in his body, from in selecting a single element in a hema the medical standpoint, must be corre tological picture for correlation with lated with the particular findings in his these many other metabolic factors. blood and his urine. I think either you correlate the whole Then, we are greatly impressed, as hematological picture or else you just physicians, with the fact that, by and do not talk about it at all. DUP050314377 22 DISCUSSION I think this is brought out very strik ingly in our own experience with lead chromate. I am sorry that I am not in a position to present our findings in de tail. I did not have an opportunity to look over our files before coining here. But we have had some very interesting experiences lately in a lead chromate plant. It is a plant that converted from zinc chromate, during the war, to lead chromate only recently. The doctor in this plant called on us not so long ago to ask for help because he was having a lot of illness. The work is incomplete, because the doctor himself wanted to finish it, and we left it to him. As a matter of fact, he probably will not do so because there has been a reorganiza tion and he is now out, I understand. However, we are following the plant closely, but we do not have the final data; I wish we did have. But we have certain information which I think is very pertinent, and which I would like to mention briefly. That is, that whatever his positive findings were, they would not have been brought to light by an analysis such as Dr. Ilarrold's, which was confined to measurements of lead excretion, lead in the air and basophilic aggregation. The changes in the blood picture found among our workers were related to other elements in the blood picture which gave us an idea, which we expect to work on, either to confirm it or throw it out. We got the impression from these blood findings, that the workers really had a very much greater depres sion of bone marrow function, on ex posure to lead chromate than what one would ordinarily get with lead oxide or some of the more soluble lead sub stances. We had a definite impression, on the other hand, that, with lead chromate perhaps because it was less soluble, workers were getting less acute lead in toxication than one would expect. Indeed, we began to wonder whether these workers were not actually getting a very different type of blood dyscrasia, from that ordinarily associated with lead intoxication. There was an unusu ally severe anemia, which was very re sistant to treatment. This troubled the plant doctor a great deal. While I do not offhand remember [and, as 1 said, I did not have an op portunity to look up our files to get the precise data on it,] it is my impression that the lead concentrations in the air in this plant ranged somewhere between 2.0 and 8.0 mg. per 10 cubic meters, which is considerably less than in Dr. Harrold's experiments; and out of line with what Df. Harrold's analysis of his experience would seem to indicate. I mention that not to question the basic thesis Dr. Harrold presents, which I think is an interesting one, but I pre sent this experience of ours because I feel that, if one is going to go beyond the mere practical use of group sam ples, for practical industrial control, one must drop that approach altogether and begin looking at the worker. There, again, I felt a great lack. Being a doc tor, I tend to look for medical evidence in a paper. I felt, personally, a great lack of medical data with reference to these people that were declared to have been uninjured, where (I do not remem ber the wording) apparently no injury to health was demonstrated. As a physician, I have a feeling that, if I were to take the first block of people in that particular row and give them a physical examination, I would turn up a lot of abnormal findings. I think we can do that with every single person that comes inLo the office for a health examination. Whether we think the findings are significant or not is another matter. Whether we think they are sig nificant enough to even tell the patient, DUPQ50314378 SOLUBILITY AND PARTICLE SIZE 23 is another matter. But, on the other hand, there are many things found. An experienced clinician looking over a lot of medical data of that sort which is found under certain conditions of ex posure tends to see a pattern, and that pattern is important. I believe for that reason, that every physical examination is, in the last analysis, an interpretation. There is no such thing as negative medi cal findings in anybody. I would like very much therefore to see Dr. Harrold present us with detailed medical data, if he pursues this investigation further, as I presume he will, because I think it is very interesting. We would then be provided with something as a basis for objective medical interpretations of our own in connection with the interpreta tion of the laboratory data with refer ence to lead excretion and lead in the air which was presented to us. I think we should get all those things together, plus detailed hematological findings not merely as to stippling, but the red cell count, the white cell count, the differential, changes in morphology and any abnormal cells which are found. We know that the blood dyscrasia in lead is characterized by an extraordi nary number of abnormal cells consider ing the fact that, judging by red cell count and hemoglobin, there is a very mild secondary anemia. The drop in red cells and hemoglobin is very small in lead workers, ordinarily. That was not true however with our chromate workers where the drop was significant ly greater and suggested to us that there was perhaps a very different blood dys crasia with which we were dealing. I hope that some time we can give you the completed data on that parti cular experience, which we are going to follow through, if the plant doctor is not going to be in a position to do it himself. I hope I have not taken too long, but these are just a few random thoughts. Dr . Go r d o n C. Har r o l d (Detroit, Mich.) : It seems as though I have to get back on the platform. I do not dis agree with Dr. Mayers in general. We were discussing my paper just before this meeting started. We have a paper which will be pub lished in the December, 1948, Industrial Medicine which, I think, illustrates bet ter than anything else our concerns and what is important. It is not our labora tory test as such, and it is not lead in itself. Put a piece of lead out and look at it forever: it will not hurt you. It is how much damage there is to the indi vidual in which we have been interested --and very much interested. We feel that, perhaps, this method of detecting damage from lead -- and I mean real damage -- by porphyrin de tection in the urine is important. Por phyrins, I think, are a measure of de struction, damage and trouble in the human organism. So, we have performed some preliminary work after thinking about the matter for a long time. We would like very much to have some easy way of taking the urine and finding out what the real damage is, as opposed to just the amounts of lead in the urine, which may or may not be fully indica tive. We are in complete agreement on that topic. As far as the lead chromate data is concerned, I still feel very strongly that when you get down below amounts of lead that are transported by the normal human population every day, we are back in the public health problems of the normal population. That may be the wrong attitude, but it is still a reason able suggestion. I do not want to take any more time, but I did want you to appreciate that we do feel, with Dr. Mayers, the data are not exhaustive in the sense we have cov ered everything--we certainly have not. DUP050314379 24 DISCUSSION We have given you, I think,'some infor of thing that Dr. Mayers is talking mation and we hope someone else can about, we do not have any. differentials do more work on the subject. We cer between those lead chromate people. It tainly cannot spend all of our time doing is purely the matter of an average. These scientific work. There is the question men did not exceed certain quantities, of making a living once in a while. around 0.1 mg., and they went down, [Applause.] again, after a period of 40 months, to Ch a ir ma n Bo w d it c h : There are so 0.039 mg., which is really lower than many among those present here who are the average industrial exposure in some qualified to further discuss this subject areas of Detroit where they use a lot that it is hard to know how to pick and of lead. We have checked that several choose. So, I think I will simply ask if times. there is anyone who would like to say Ch a ir man Bo w d it c h : We still have something further. two or three minutes left in this dis Dr . Al s o p h H. Co r w in [Johns Hop cussion period. kins University, Baltimore, Md.]: I Mr . H. J. Weber [American Brake should like to know if there has been Shoe Co., Chicago, 111.]: 1 would like any attempt to correlate, in these lead to mention our experience in a brake chromate cases, the mouth-breathers lining plant where we deal with lead with the nose-breathers, because that sulfide. While the lead-in-air concen might make a very great difference in tration might be as high as 10 mg. per the amount of lead absorbed. 10 cubic meters, we have not in five Dr . Har r o l d : As far as the cases years been able to demonstrate any are concerned--and that is one reason symptoms or signs of lead intoxication why we do not have exhaustive medical in the employees exposed. data--these men were processed through Our experience also seems to bear medical departments and they went out Dr. Harrold's statements about par through physicians' hands, and they did ticle size. In our machining operations the work on them. These data refer to where the particle size is large we do the same men over a period, in the case not have any cases of lead intoxication of lead chromate, of 40 months; that is whereas in melting operations we do. three and a quarter years. There was This indicates that particle size has a ji nothing wrong with them, at least that definite bearing on lead intoxication. the physicians could find in their normal Ch a ir ma n Bo w d it c h : Is there any check-up, without going into extra, de thing further? tailed, scientific observations. One hun Our next speaker has been in general dred eighty-five men are quite a number and industrial practice in East Chicago to work up in a detailed way. They are since 1912 and has been specializing practical evaluations by the physician there in lead absorption and in alumi in charge, of the man's suitability for num therapy. work under the criteria of his own A member of the staff of St. Cathe medical examination. rine's Hospital and a former member of The mouth-breathers and the nose- the Indiana State Board of Health, he breathers in this particular instance were is consultant to the American Smelting not determined. As I say, we do not & Refining Company, The Eagle-Picher have and we did not have any suggestion Company, The Glidden Company and of difficulty. On that basis, without, other industrial organizations in the again, having done the exhaustive type East Chicago area. Dr. David R. Johns. -sE DU P050314380 ^r THE TREATMENT OF LEAD POISONING--PAST AND PRESENT By DAVID R. JOHNS, M.D. Consultant, American. Smelting & Refining Co,, Eagle-Picher Co., and the Glidden Co., East Chicago, Ind. I might say, before going on with this paper, that I do look at this picture from the general practitioner's stand point, having been in the general prac tice of medicine since 1912 and having been associated with the lead industry for about 25 years. I see these men and look at them from the standpoint of their family phy sician and as a general practitioner. I think that, while as a physician I might claim some credit, I do believe that a great deal of our success has been due to the good housekeeping and the en gineering features in the various plants. I have had many battles with them and, probably because of those battles, we have had better engineering and better housekeeping. I, as a physician, visit my plants, that is, go out through them at regular, stated intervals to see what the condi tions are in that plant The subject assigned to me today should offer little difficulty to any phy sician who has spent some years in the lead industry. Looking back over 25 years of being closely associated with this industry, he should at least find a routine of treatment, from the many which have been suggested and prac ticed, which would serve him well. The advent of the safety first move ment about 40 years ago did much for the safety of the worker in industry in respect to traumatic injury but it was 20 years later before a great deal of attention was focused on occupational diseases. May I at this time pay tribute to the physicians who have labored so valiantly in this field of human en deavor, the conservation of a human life, the most precious asset in this world of today. So this morning may I intrude a little in saluting those pioneers. Dr. Alice Hamilton, Dr. Aub, Dr. Fairhall, Dr. McCord, Dr. Kehoe, Dr. Lanza and many others. We of today are deeply indebted for their untiring ef forts in the years gone by. Lead poisoning dates back to antiqui ty and much has been written concern ing it for several hundred years. Today, with the widespread use of lead in indus try and the ever increasing demand for its use, it still is a major potential cause of occupational disease among those who must come in contact with it in their daily work. But I, for one, have seen very little lead poisoning in the last 10 or 12 years. Lead absorption we do encoun ter in the course of our work, and it is this phase of the subject which I believe really concerns most physicians in the lead industry. To me there is only one real type of treatment and that is pro phylaxis. I will not discuss the prophy lactic phase as this will be most ably done by other speakers on this program. The treatment of lead absorption or lead poisoning, if a case is permitted to go to that latter phase, begins at the first sign of absorption as observed by the physician in his regular routine in spection of the worker. And I might say that these men arc inspected month ly; blood smears are taken, and the men are interviewed. I believe there is no phase of occupational medicine where a man's statement means as much as when one is determining whether he has lead intoxication. Truly if we are to be our brother's keeper there is no phase of human life to which it applies more intimately than in the duties of a plant physician. If evidence of lead absorp tion is detected, and I mean early signs, 25 DUP050314381 26 JOHNS such as constipation, a high stippled gineering skill, the monthly inspection count, a moderately elevated lead urin and blood work is the outstanding part ary level, or lowered hemoglobin, or red of the treatment of lead absorption. cells, 1 do not wait for his blood or Naturally, other conditions such as con other laboratory findings to be re stipation and low hemoglobin should be checked in a week or two but advise im treated and properly checked. mediately a quick inspection of his job There have been many ideas about so as to correct his hazard but, more the treatment of lead poisoning; various often, recommend a change in his em methods have been advocated and like ployment to a less hazardous location wise many have been tried, and practi in the plant. This is the most essential cally abandoned. Among these are sul part of his treatment; to wait for a blood fur, sodium thiosulfate and, more re count or a lead urine, possibly a month cently, vitamin C. However, one of the later, to determine whether he should he oldest, magnesium sulfate for constipa moved to another job, is to be derelict tion and potassium iodide for lead elim in one's duty. This procedure and noth ination is still used to good advantage ing else is usually all that one has to do by many physicians. The diagnosis and a month later the worker is already "lead poisoning" to me implies the pa on the way back to normal health. Pro tient has several of a number of symp crastination in these measures is what toms, namely--pallor, nausea, colic, leads to lead poisoning, and I, for one, generalized aching of body and joints, see no need for a case of lead poisoning sleeplessness, changes in the hlood pic in a plant which avails itself of a regu ture which consist of a secondary anemia lar attending physician, who has had with relatively high stippled count, and some experience in the field of plumhism moderate or high lead urinary levels. and has adequate laboratory facilities With several of these symptoms present, at his command, and with the determi active treatment should be instituted at nation of the plant officials and safety once. The treatment as outlined by Dr. department to do their part. I may add Aub some years ago has been found here that it is the physician's duty to extremely helpful. This consists of im ascertain that a man's job has been mobilizing the lead present in the blood changed and to see that he has been stream by means of the metabolism of given sufficient time to recuperate in the calcium by which the lead is stored in new location. I will also add that the the long bones of the body. Calcium companies with which I am associated gluconate, intravenously, appears to act have cooperated with me in a very satis very well and a high calcium diet is pre factory manner. The job that industry scribed to be given when nausea sub did in the traumatic field, they will do sides. Intestinal drainage by enema at again in the occupational disease field. first, then salines are administered as To the above treatment I would add the nausea lessens. The intense pain of a complete physical examination of all lead colic is controlled by morphine and lead workers each year; surely with all atropine, and also demerol. The sec of the pathology attributed to lead some ondary anemia is treated with hemavaluable information should be ob tinics and vitamins. tained. This physical examination In those few cases which we treat for should not be confused with the month lead poisoning the following orders are ly inspections, interviews and blood what I give: work. After good housekeeping and en 1. Morphine and atropine or demerol DUP050314382 TREATMENT OF LEAD POISOMNG 27 for pain if severe. 2. Daily enema, repeat if necessary. 3. Calcium gluconate intravenously and orally. 4. Sodium phosphate (Fleets) 3 times daily when nausea subsides. 5. Heat to abdomen. 6. Complete blood picture. 7. Stop enema as bowels begin to function. 8. Soft diet the first two or three days, then full diet. 9. Liver and iron for secondary anemia. 10. Patient to be up as soon as colic subsides. 11. Give patient sufficient time before return to work. Inseparably tied up with the treatment of lead absorption or lead poisoning is the evaluation of the lead blood smears or lead urines. I have used the blood smear for stippled cell counts for 20 years and it has served me well. Along with the weekly inspections and inter views, I have had no reason to regret its use. We see some cases of extreme lead absorption and practically no lead poisoning with the exception of a rare case of lead colic. I have no quarrel with those who use the lead urines as their principal guide but I do believe that there is a tendency at the present time to raise, in my opinion, the per missible lead level to, perhaps, too high a level, the normal lead urine being 0.05 mg. per liter. Why raise it five to eight times that value? I, for one, am some what afraid to do so. The question of deleading a patient is one in which opinion is divided. Some patients I have deleaded and others I have not. I can see no appreciable ad vantage for those who have been de leaded over those who have not. As the lead hazards in industry are lessened and more careful checks are made of each worker exposed, it appears to me that perhaps we can put aside the de leading. Surely nature will eliminate if the exposure is corrected. There is one item which to me is of some importance and I would like to present it to you with the hope that it may be a part of your discussion. Should a man with active syphilis (positive serology) but with no external lesion be employed in the lead industry? My view's are that he should not be allowed to w'ork in lead hazard. Lead and syphilis appear to have a marked affin ity for the central nervous system. Why should we permit a man to suffer the possibility of a double bombardment? Industry should be concerned as to whether a central nervous lesion was due to lead as an occupational factor or whether syphilis was the etiological factor. Lastly there is a question which I have been asked many times. Many writers and textbooks have answered it, but I have not agreed with them. The question is whether a man who has once had lead poisoning should return to the same industry. My policy has been to permit his return, hut if again in a period of six months he shows signs of lead absorption, to advise him to seek different employment. In conclusion, may I again point out that my remarks have centered chiefly about prophylaxis and lead absorption; of lead poisoning I could say it has been encountered only on rare occasions. If the officials of our companies, together with the safety engineers, and the medi cal department keep ever before their eyes that slogan enunciated 40 years ago, by those pioneers of safety, "Eter nal vigilance must always be the price of safety," then the worker in the lead industry is in safe hands and the saying written many centuries ago, "Thou shalt be thy brother's keeper," has come to pass. i DU P050314383 28 DISCUSSION Ch a ir ma n Bo w d it c h : We have in vited to lead the discussion of Dr. Johns' paper a man who, though of not quite such long experience, has been a spe cialist in surgery and urology since 1925 and has had particular interest in the problems of lead workers. He is a past president of the Ameri can Urological Association and a wellknown writer on subjects of public health. He is consultant to a large num ber of industries and insurance com panies in New Jersey, and is medical director of the National Lead Company's plant in Perth Amboy, N. J. Dr. Wil liam C. Wilentz. DISCUSSION Dr . Wil l ia m C. Wil en t z [National Lead Co., Perth Amboy, N. J.]: The subject of lead poisoning always arouses great interest wherever one travels. I am particularly delighted at the simple manner and calm reasoning that is evi dent in the paper we have just had the pleasure to hear. There is lacking that "Pluinbo-Phobia" attitude which is so prevalent throughout our literature. This is very significant because it indicates a definite and wholesome trend away from the old days when the disease was more widespread and was responsible for great numbers of cases of temporary and permanent disability as well as deaths. This situation was more or less recog nized by the leaders of industry but the medical and allied professions were ig norant of the physiology and causes of this disease in addition to being unfa miliar with the methods of treatment. Today, although there are still many cases of temporary disability, there are fewer and fewer cases of permanent dis ability and rarely a death. This is a practical demonstration that sincere ef forts have been made and are being continued to diminish and eliminate this hazard. The results so far are grati fying. The following are some comments which I shall take the liberty of making so as to clarify some of the important factors mentioned by Dr. Johns: 1.I wholeheartedly agree that only one real type of treatment exists and that is prophylaxis. But at the same time, I know that until such time as prophylaxis is practiced properly and efficiently, our prob lem still remains to a great measure a matter of treating lead poisoning with a therapeutic regime directed towards (a) overcoming the intes tinal colic and discomfort, (b) cor recting the resultant anemia, (c) making the patient symptom-free with no disability remaining and (d) returning the patient to a re munerative position as soon as pos sible. 2. The question oj changing jobs of individuals who are in this ex posure is, of course, important and vital, but I cannot help but state that in my experience, one is con stantly confronted with the prob lem of determining each employee's tolerance to dusts and fumes and no matter how vigilant we may be, the occasional case arises which develops so acutely that it even astonishes us. One way to over come this problem may be by short ening the work day to six hours and putting in six days a week in stead of five. This has been rec ommended by Dr. Brockway of our organization. 3. We rarely find it necessary to use morphine or its derivatives to con trol pain. We use antispasmotics DU P050314384 TREATMENT OF LEAD POISONING 29 such as syntropan, trasentine with or without phenobarbital. We must not forget that the administration of calcium intravenously not only immobilizes the lead but also acts as an antispasmotic in its own way. 4. We utilize magnesium sulphate as the cathartic of choice. We find no objection to the use of phosphosoda; in this connection it might be said that we rarely find it necessary to employ enemas. 5. We encourage hospitalization in these cases as a rule because we know of no other place in which treatment can be administered around the dock. It is our opinion that this is the best method of get ting the quickest, most dramatic and permanent results. 6. We never prescribe iron, liver or calcium orally during the acute stage--which means while they are confined to the hospital--because we feel that the body will not be able to absorb these medications until the toxic effects of the lead have been overcome or are at a standstill and the metabolic pro cesses of the body have again be come adjusted. 7. We are opposed to returning these employees again to exposure. It has been our experience that these individuals will return with a more severe episode than the original attack. 8. We never employ deleading and wholeheartedly agree with Dr. Johns. Do the numerous methods advocated by deleading sponsors work? Kehoe has stated that "there are grave doubts whether or not the elimination of the toxic agent can' be materially accelerated by artificial means," and he further feels that "this elimination can only be accomplished spontaneously over a considerable length of time." Aub and his associates concluded that "complete deleading cannot be done." Oliver and many others have confirmed this finding. It is most interesting to note that prac tically all the advocates of delead ing admit that the procedure is dangerous and must only be at tempted under definite and specific circumstances. Johnstone noted that "this procedure (deleading) has been discarded due to the be lief that lead is excreted from the body by normal physiologic pro cesses." It is admitted by its ad vocates that rapid deleading is to be avoided and therefore it is ad visable to immobilize the lead in the bony structure during the acute episode. They also state that de leading is then advisable since the liberation of this stored lead is an obvious factor in the onset of toxic lead episodes during metabolic up sets. It is this latter statement which apparently is the principal argu ment used by the advocates of de leading. It almost sounds convinc ing were 'it not for the fact that in our experience in treating over 60-odd cases of lead intoxication and hundreds of absorption cases, not one case has presented itself where any such metabolic upset produced any liberation of stored lead to such a degree as to inca pacitate the individual. We admit that some conditions can produce some free circulating lead into the blood stream but the results are negligible and the individuals are symptom-free as far as lead is con cerned. Belknap has stated that "after an absence from lead exposure of one to two years, lead intoxication prac tically never develops." Aub has DUP050314385 30 DISCUSSION stated that "from a theoretical standpoint, deleading is advisable-- but from a practical point of view, the answer is dependent on which procedure will advance most promptly to a recovery of health." We agree wholeheartedly with this declaration but one can hardly miss the implied suggestion in this state ment that perhaps deleading is not advisable from a practical point of view. And that is exactly what you and I are interested in. In other words, it just doesn't appear to be the method of choice. It has also been stated that cir culatory lead may cause tissue dam age but stored lead in the bones produces no deleterious effects. If this is so, and so far as we know, it has been accepted by most men in this work, then what is the justi fication for employing a method of therapy which is acknowledged by its advocates as dangerous and un certain as to its ultimate results? We know that no method is avail able for the complete removal of lead from the body and further more can see no reason why this is desirable under the circumstances when it is well recognized and ac cepted that there is a normal lead metabolism governing the intake and output of lead from the body. It is our opinion that no remedy has been found to justify the dangers inherent in deleading. It is our con tention that it is more advisable not to employ deleading procedures in view of the fact that simple im mobilization of lead within the skeletal structures of the body is the most rapid and safe method of bringing about "a state of well being." From our point of view, we do not advocate deleading because (a) it is admitted as a dangerous pro cedure by its advocates, (b) pro longs hospitalization, (c) prolongs disability, and (d) results are un certain. On the other hand, calcium immobilization therapy is (a) sim ple and safe, (b) shortens hospi talization, (c) shortens length of disability, and (d) results are cer tain. 9. As to lead urines -- I simply would like to confess that the estimation of lead in the urine, stool and blood has never impressed me with the same importance as some men feel. The real information is to be ob tained from our blood counts, smears, and the clinical picture of the patient himself. 10. I agree with Dr. Johns about his thoughts relative to the non-employ ment of luetics in a lead exposure j ob -- we were forced to employ a number of these individuals dur ing the war and it is interesting that our experience was most satis factory-- perhaps we were just plain lucky -- I still feel that Dr. Johns is right. I would like to mention at this point that the fellow who worries me a great deal is the employee who gets drunk after each payday -- that's the man whose count gets thrown completely out of line -- anything could happen to him, but never does, for some reason or other. It-is my belief that the treatment of lead poisoning is very simple and very satisfactory -- that we have at our dis posal definite and specific therapeutic procedures which if carried out properly will bring excellent results and will leave no disability of a permanent nature. Ch a ir ma n Bo w d it c h : Again, there are so many here who may well wish to contribute to this discussion that I will mi m\ I DUP050314386 TREATMENT OF LEAD POISONING 31 simply invite anyone who feels so in clined to speak his piece. Dr . D. J. Lau er [Kettering Labora tory, University of Cincinnati, Cincin nati, Ohio]: Dr. Johns began his study of the treatment of lead poisoning the year I was bom. [Laughter] I was most interested to hear what he had to say. It sounded quite solid. What I wanted to do this morning was to discuss Dr. Wilentz' opinions on deleading. I quite heartily agree with his thoughts. My agreement is based upon some observations we have made on individuals, with the idea of de termining whether or not we could "de lead" them. We have examined them very carefully, doing in addition X-ray examinations and complete blood studies. In a control period we have collected 24-hour samples of urine each day for a number of days. We have collected all the feces. We have analyzed duplicate samples of blood daily for their lead content and, of course, daily stippled cell counts have been made. After the period of preliminary (con trol) observations, I started to admin ister ammonium chloride in divided doses at the rate of 6 gr. per day. In one case, I doubled the dose to 12 gr. a day in divided doses, and the patient tolerated it. Then I stepped it up to 14 gr. a day. We were collecting all urine, feces and blood samples daily. In addition, I determined the carbon dioxide combining power of the blood plasma of the individual, before we began ammonium chloride. I put him on a sodium-free diet of bananas, boiled rice and water, to make sure that we would remove the sodium ion as much as possible so as to produce an acidosis which is said to cause deleading. Finally, after he had been on 14 gr. per day, he began to get a little short of breath, and developed other symp toms of acidosis. At that time his carbon dioxide combining power was 37 vol umes percent, and I withdrew all medi cation and let him go back on his ordi nary diet, continuing to collect 24-hour samples of urine, feces and daily dupli cate blood samples and making daily stipple counts. At the end of four days, dioxide com bining power had returned to 52 vol umes percent, or normal. In the study of products of the urine, feces and blood, the analytical data on the blood and excreta demonstrate that there was no deleading and no storage of lead. The experimental period re mained like the control period with re spect to lead output. I want to continue further observa tions on this because the number of cases is somewhat limited. We have studied other agents that are said to promote deleading, such as potassium iodide, and so on, and we want to study them further. We have failed to find evidence of deleading under the influ ence of these agents. I hope to say a little something on BAL tomorrow. We have done some studies on that. Ch a ir man , Bo w d it c h : All of this augurs well for a spirited debate to morrow morning. Who is the next con tributor to this discussion? Dr . Wm. G. Wo o d [National Lead Co., St. Louis, Mo.]: I wondered why the basophilic aggregation has not been mentioned in the treatment of these two cases. Have you used the basophilic test? Dr . La u e r : I have used the basophilic aggregation test in the past. I have not used it for some years. We just merely used the stipple count, among other things. Mr . G. C. Wal t er s [National Lead Co., Chicago, 111.]: He asked about the basophilic aggregation count. We used the basophilic aggregation count for DUP050314387 32 DISCUSSION about four years, along with the stippled cell count. While there was rather a constant correlation, the graph line would separate at times. The reason we abandoned it was because of the various staining elements that threw us off with a light field scope. With a dark field scope it might he different. We found, even in normal individuals, taking the same counts, in a week's time they would differ from the day the stain was made. There may be a better stain. We used those recommended by McCord and several that were recommended in Industrial Medicine, but we could never find constantly good counts and as re liable as the stippled cell count. It would cause a great deal of argument on both sides. Ch a ir ma n Bo w d it c h : Would you care to comment on that, Dr. Mayers? Dr . Ma y R. May er s [New York State Department of Labor, New York N. Y.]: I have never worked with basophilic aggregations, so I would not be able to say from my own experience. But it is my feeling that, when you are dealing with the blood picture in lead poison ing, it is the very same thing as dealing with any other blood dyserasia in terms of the technics used for interpreting the blood picture. It seems to me the sim pler thing to do is to take the regular smear and stain it and examine it for stippled cells along with all other ab normal cells as one does with every other blood disease. I would like to stress very much the fact that, in our experience, stippling per se is not too important. In a par ticular smear it may be very unimpor tant. The fact that, with a very slight drop in the hemoglobin and the red cell count, you can get nucleated red cells, or marked changes in size and shape of red cells, can be much more significant in a particular case than the stipple count. I do not like to feel that we should stress stippling too much in general. That is why I have not even tried McCord's basophilic aggregation test It is a procedure which is out of line with the general diagnostic approach to blood diseases. This approach should be just the same in lead poisoning as in any other blood disease, in my opinion. Ch a ir ma n Bo w d it c h : Ho w about you, Dr. Johnstone; would you care to enter into this discussion? Dr . Ru t h e r f o r d T. Jo h n s t o n e [Consultant in Occupational Medicine and Industrial Hygiene, Los Angeles, Calif.]: I do not know of any disease, occupational or otherwise, about which, so much nonsense has been written as lead poisoning. I particularly object to the carry-over from the older literature which we constantly see repeated by writers today. I have in mind a monograph on lead poisoning which was fairly recentlypublished. This monograph quotes all of the available information about lead poisoning but fails to discriminate be tween statements which have been proven to be scientific and those which are merely conjectural. It is very con fusing. My experience with lead poisoning is different from most of your physicians here who supervise the medical care in large plants. You probably see very few cases of lead poisoning and because of that there is a growing tendency to be lieve that lead poisoning is on the de cline. I disagree with such an assump tion. In the area where I practice we have a great number of reclaiming plants, smelting plants and a large num ber of small companies who manufac ture batteries. It is with these small companies that we have a fairly high frequency of lead poisoning. Of course, we occasionally see individuals with lead DU P050314388 TREATMENT OF LEAD POISONING 33 poisoning who work in larger com this fellow got was spinal taps to relieve panies where they should have better his pressure. After he was discharged hygiene. 1 followed him for a period of four or As far as - symptoms are concerned, five years. On one occasion he had a almost all of these cases are mild. In blood stream infection. At that time we twelve years I have seen but one case were able to determine the lead in the of lead encephalitis, and only two cases blood and urine which revealed no in of wrist drop. The remaining cases, as crease above the normal. In other words, I have said, are mild with an occasional we saw no release of lead during his moderately severe case. There are sev acute illness. The same man was seen eral reasons for this. because of a severe pneumonia, and at In the first place, the average work that time also he had no increase of lead ? man is conscious of lead hazards and he in his blood or urine. is particularly aware of the fact that It is my opinion that the simpler we stomach-ache may be a symptom of lead attack this problem the better, and poisoning. Therefore, today these men when we are writing about it in the report to a doctor fairly early in their literature we should cut out a lot of the disease. Also, the representatives of nonsense about the sequelae of lead labor unions within these plants are poisoning. diligent in seeing to it that the workers Dr . Al b er t S. Gr ay [Director, get early medical care. Bureau of Industrial Hygiene, Connec As far as the treatment of lead poison ticut Department of Health, Hartford, ing is concerned, we actually do not Conn.]: I agree entirely with Dr. John treat lead poisoning per se. We with stone that it is the small plants where draw the man from exposure, and never we get these cases. give him morphine for his colic or pain, I would like to ask Dr. Johnstone, or nor do we use any other antispasmodics anybody who is here, if they have any except calcium. We do not find it nec plan for industry to use as a routine essary to hospitalize these patients. I plan. As an administrator of industrial have not hospitalized a case of lead hygiene activities, we try not to lean poisoning for a good many years. We down too heavily on industry but to do treat them for their anemia, after require those things that we realize are the initial calcium therapy. best for the industry and the worker. Just before coming to Chicago I One of the things that we have to do, looked over our record sheet to deter particularly in the smaller and the mine the average length of disability of medium-sized industries, is to suggest our cases. This may startle you, but some routine course of procedure. our average period of disability for Most of the plants in Connecticut, and these men is three weeks. At the end I suspect in many of the states, are ad of that time we send them back into an ministered to by physicians. But you occupation where there is no lead haz know that they do not get paid for look ard. There have been some cases with ing over the plant, and they are very a longer period of disability, but as I busy men, usually men in general say, the average is three weeks. practice. We had one case of lead encephalitis, We find, for instance, where we must as I previously mentioned. He was have some routine procedure, where the hospitalized, of course. This was a mim. men should be examined and certain her of years ago. The only treatment needed work done--I am not going to DU P050314389 34 DISCUSSION say just what we have them do, because I want some of you to tell me what we ought to have them do--it is necessary to follow up whatever procedure is re quired continually. We .find frequently that the plant has not sent the men to the doctor. We go to the doctor, and he says, "The plant did not send them to me." The plant says, "Well, the doc tor didn't ask for them." So, we con tinually have to follow through to see that the necessary work is done. Then, when the work is done and a report is provided there is frequently no attempt to follow through and apply the results of the examination construc tively. We look it over, go to see the doctor and if some results are high, may suggest that some of the men should be transferred, and he is usually agree able. We go to the plant if results are high to check up on control. There does not seem to be very much interest displayed by the doctor on call in the small and medium-sized plants to follow through. He just does the examination as a part of his, if I may say so, on-call job, and there the matter rests. I would like to hear from some of you gentlemen who have some plan which can be given to the plants re specting the procedure they should fol low. Should these men be examined once a month, once in three months? Should they have a physical examina tion before they are exposed to lead, one or two examinations, to establish a base line for their blood examination or their stipple cells, or aggregation? I think these matters are very im portant. You folks in the lead industry undoubtedly, at times, object to what we State people want. If we knew what you think is desirable, and you knew what we feel is necessary, we could get together on something that I think we would both feel was more constructive. We examine the environment of lead exposure very carefully. We have good engineers, doctors and chemists. We try to control exposure to lead. We have found, as a rule, that industry accepts constructive recommendations for such control but things will happen even on the best engineered job if you do not follow through. A plant that has a good vacuum cleaning machine and a poor foreman will still use a broom. A worker will stick his head under the hood, and he will refuse to wear his respirator or leave it off on certain occasional jobs he has to do. On many occasions, you know that the best engineering will not permit you to sleep soundly if you do not follow through. Dr . Jo h n s t o n e: I want to answer Dr. Gray's one question, the first ques tion he asked. I do not know how it is in the rest of the country, but out in our part of the country a good many of the plants sup ply the plant manager with the normal stipple count, then the employees at in tervals are sent to a laboratory and when the laboratory report comes back the plant manager takes it upon himself to decide whether this man has too much lead in him or not. [Laughter] The second big fault is that a great many plants hire a two-dollar doctor, and they get a two-dollar examination. They will send employees around the corner to a physician who has never been in the plant. He gives them a brief and cursory examination and then re turns them to their work. The Lead In dustries Association should encourage their members to employ experienced physicians and to pay a worthwhile fee for the examination of their men. I do not know how far the Lead In dustries Association is going, to educate the little man. As I look through the list a& TREATMENT OF LEAD POISONING 35 of this membership it is apparent that Our routine is, of course, that every most of your members employ physi man receives a pre-employment exami cians thoroughly cognizant of this prob nation, including a complete blood pic lem, but it is the little industries that do ture and urinalysis. Then, every man not appreciate the problem, and that is who is exposed to a lead hazard is seen where the big job in education lies. The by me once each month. I see groups of second job, of all things, is to educate about 15 or 20 men each morning at the doctor. the plant. Every man in a lead exposure Ch air man Bo w d it c h : I see Dr. Johns is smeared monthly. He is seen by me is itching to make a further comment and talked to, with a general inspection but, before he does, I want to add to and questioning. We seem to get along what Dr. Johnstone has just said. very well on that basis. We are doing a I shall always remember, some years number of lead urines, also. But I have ago, talking with the physician of a relied, in the greater part of my ex large plant of a very large company up perience, on the inspection and examin in my former part of the world, a plant ing of the men, and the blood smears. which had a very definite lead hazard. Each man in the plant is examined He said to me, "Mr. Bowditch, how yearly. He gets a complete physical ex about this urine sulfate test for lead amination. I examine about five or six poisoning?" men in an hour and one-half. Now, Dr. Johns, would you like to add To answer this gentleman, our routine something? is: I visit the plant twice a week. Every Dr . Jo h n s : I entered the lead field man in a lead exposure is seen by me in the days when, if I visited a plant to monthly. I am the one to say whether call on the superintendent to talk over a man's employment is changed, and I some matters, he would look up and have had some difficulties in that matter, down the hall to see if anybody had though, I think, as I said before in the seen me come into his office. [Laughter] paper, that my insistence that a man's Also, the stipple counts and anything employment be changed has stirred them else which releated to lead intoxication up on their engineering ends. were kept in the superintendent's safe. I do want to say, and I still believe Nobody saw' them but the doctor and that we are derelict in our dust counts him, and then, later on, the safety man. in the plants. They are not made fre But I have gone along for 25 years quently enough. 1 think, if there is one in this phase, and I can say that man thing that we must do in the lead indus agement has gone along with me. I try, it is to sell management on the fact think, by far the greater part of the that we should take more dust counts. credit for so few lead poisoning cases, The men are changed in their employ in my experience, has been due a great ment, and I see that they are changed. deal to the engineering and good house We have a record of every man who I keeping and the inspection of the plant advise that his work be changed, and I by the physician. check. If he has been put back on any It is true there are small plants in regular work, he must come in, and I which a physician does not visit, only 0. K. his going back to his old employ on call, but, in my field, I visit each one ment. That is the regime that we follow of my plants twice weekly and spend in the three plants that I take care of. about an hour and one-half to two As far as seeing lead poisoning, I can hours at each plant, say truthfully, in the last eight years we DUP050314391 36 DISCUSSION have had no cases that have gone before the Industrial Board in the State of Indiana from the three plants that I take care of. I think we are doing a job there, but it has been in cooperation with plant management and the doctors. I would estimate, roughly, the num ber of men who are exposed to a lead hazard in all three plants, at about 500. Dr . Gr a y : I would like to say, I think some time some clever man, who has heen at the job as long as you have might tell us the differentiation, the di viding line between lead absorption and lead intoxication. We talk about lead absorption, and somebody says, "I don't treat any cases of lead poisoning. Some of the fellows have colic." And somebody else says they don't treat any cases of lead poi soning, "but a fellow isn't feeling well. Has he got lead poisoning?" I do not think that we are very clear in our delineation between lead absorp tion and lead poisoning. As for myself lead poisoning is sufficient absorption to produce signs and symptoms, but many apparently do not subscribe to this definition. Dr . Jo h n s : When any man. comes to me and, when I question him, he tells me that periodically he has intestinal cramps, I regard him as a case of lead poisoning. But for lead absorption, I use this as my threshold: If a man has over 1,200 stipple cells per million red cells, his work is changed immediately. I grant you that, in your textbooks, they say 300 or 400 is permissible but, after years in this, I have seen no cases where we got into any trouble about it, or the man has been ill where he has not been permitted to go along over 1,200. In our stipple count we call that 0.12, and his work is changed, if he goes over that. Dr . Gr a y : Your stipple is 0.12? Dr . Jo h n s : That is 1,200 per million red cells. Dr . Gr a y : It runs about the same with the aggregations. Dr . Jo h n s : We do not do the aggre gations ; we do the stipple count. I think there is nothing more important than to bring your man in periodically, once a month, and talk to him and find out what he is doing. Dr . Gr a y : I think that is very im portant, Dr . Jo h n : I think there is no phase of medicine where you have to take the man's history as much as you do in lead absorption or lead poisoning, because what he tells you is pretty nearly what is happening. Dr . Gr a y : That is unfortunate in the small plant. You usually cannot get that. Dr . Jo h n s : That is right. I will agree with you. Mr . Wa l t er s : Some years back we had to make the stippled cell counts twice weekly, in order to keep ahead of the men, but it was in a very bad spot and has since been removed. We would never have been able to keep ahead of them if we had made the counts only once a month. Dr . Jo h n s : We do them routinely, but every man exposed to a lead hazard will be smeared once a month. Mr . Wa l t e r s : Some of the people here might be from small plants and I would like to say that we should not belittle any one technique that they may use. For instance, some plant might employ only one technique, where a larger plant might employ five or six very elaborate techniques, including tests for lead in the feces, urine, blood levels, etc. So, that the small plant should not feel that, because their par ticular technique is not complete within itself, to assume an attitude that "Oh, well, we will just forget it entirely," because one technique is a tool and it should not be dropped. It should be TREATMENT OF LEAD POISONING 37 built onto and I believe progressive Johnstone about hospitalization. We small plants will build to it. have talked about this before. We hos Dr . Jo h n s : I have been very for pitalize our cases of lead intoxication; tunate in having the same man examine I mean the really sick fellows. It varies my smears for 22 years. That, to me, as to degree. The doctor says that we means a great deal. When I send smears must see sicker patients. I am willing to the hospital, I am somewhat skep to take that as the answer, because I tical. Our man finds stipple cells and think we hospitalize 65 to 70 percent of the hospital does not find them. I think our cases, and we are delighted to do it, that is because they do not see very because, you know, it is the one place many slides with stipple counts, but, where you can really do a job. You fortunately, I have had our technician know they are going to get the medica for 22 years, and he examines about tion. You certainly cannot give them 6,000 slides a year. one shot a day, and expect to clear up Dr . Wil l ia m C. Wil en t z [National the case quickly or satisfactorily. Lead Co., Perth Amboy, N. J.] I would I just send them to the hospital. Many like to comment upon what Dr. Mayers of these men I was unable to send be said before. She is taking no chances cause they would not go. It is a long when she talks about taking the whole procedure if you do not hospitalize, and picture as the horizon. Do not worry I like hospitalization because of effi about the stipples or do not pay too ciency. much attention to it is not quite fair Dr . Jo h n s t o n e: Ho w long did you a remark. say the disability is. Doctor? Dr. Mayers, I think that, in lead, stip Dr . Wil en t z : An average of three pling is so attached to the problem, to weeks. Our ambulatory cases are usually the poison, you cannot belittle it, and I disabled about 15 days; on our hospital know that you do not, but I do not want cases, the average disability is about 30 anybody to get the idea that you feel days. We are talking here of lost time that way about it. from work. ^ It is so intimately attached, if you I would like to make another remark. do not pay attention to it, you may be I said something about it before. It lost. It is a big thing. Lead and stip seems to me that we should not confine pling go hand in hand, so much so that, the information that we get from our when you have your cases in a hospital, work just to periodicals that go to you what do you find? You find the tech and myself. I think that is one of the nicians in the hospital do not know what mistakes that we make. I think the in a stipple cell looks like. How often do formation that we have, that we get, they see it? I don't know, but I do ought to be placed in periodicals that know one thing about it, when we send have a large circulation, so that the people with lead, they learn on our other fellow who may occasionally meet patients. They don't know what stippling these cases but who does not know lead looks like. We have, of course, our poisoning when he sees it, will get some technicians who are trained for it. But, of this information. so far as I am concerned, stippling is After all, we are talking to each other. part and parcel of the entire picture and I do not know how much good it does, it is terribly important. You have to but it ought to do us a lot of good. learn for yourself how important it is. There is a limit as to how much good I would like to say something to Dr. it can do. Many of you people could DUP050314393 38 DISCUSSION come up and say what we have been ears, because in some meetings where saying this morning, with just as much I have gotten up and ventured even to authority because you have equal ex mention the word "stippled cell" or even perience. such a thing as a lead line, I have often I would like to see a more widespread been properly put in my place. dissemination of this information, in In that connection, I recall at the stead of confirming it just to you and Boston meeting of the A.M.A., when to me. this whole subject was explored, we had Dr . El s t o n L. Be l k n a p [Globe- a visiting physician from England-- Union, Inc., Milwaukee, Wis.j: I hope I believe his name was Dr. Lane--whose to say a little more this afternoon and first comment was, "I have listened all in a little more connected fashion, but morning and I haven't heard anybody I felt I could not miss this opportunity mention the subject of a lead line." i of congratulating two men who are Indeed the papers up to that time had i physicians and clinicians on an excellent been largely laboratory and non-clinical. grasp of the subject, namely. Dr. Johns In regard to stipple cells, I received and Dr. Wilentz. It is not because their a letter from the director of probably ideas and my ideas are exactly alike. one of the largest storage battery com We have minor differences. But what panies in England, from the assistant impressed me was the opinion of men medical officer, Dr. Scott, who had writ who know their way around in the field ten over here asking our practical pro of industrial medicine and who have cedure in controlling lead absorption seen many cases of lead poisoning, se and lead intoxication in storage battery vere cases in the old days, less severe workers so that they are able to keep now. healthy and at work. He was wondering I did not want to let the opportunity if, perhaps, they were getting behind the .! pass without paying my deep respects times over there in England and not to both of them, and also to the other using up-to-date laboratory work. men who were the discussants, such as In reply to my letter he said that he Dr. Johnstone, who also has had a great has approximately 800 men under his deal of practical experience. supervision. He says, "On the average, Sometimes I have been so discouraged we may transfer, temporarily or perma in a meeting of this kind that I did not nently, ten to fifteen men a year on the say anything. [Laughter] I would see grounds of sub-clinical plumbism." He men get up who were not physicians, does not let them go to the point of and some men who were physicians-- disabling lead intoxication, however. which was, perhaps worse [laughter] In regard to this subject of stippled --and make comments showing that they cells, which he approves of, as our had no clinical grasp of the subject of speakers have today, and which with lead poisoning. After all, there is such hemoglobin study, they use largely in a thing as lead poisoning. Men do be controlling their problem, he says, come ill and sick with lead absorption. "Having studied your and Dr. Fairhall's We say they have lead intoxication. views, I feel that our present methods Fortunately, lead poisoning or true lead are very much in agreement and that intoxication is much rarer now than it there is no good reason for changing used to be. them." The emphasis that we have heard Whenever I have talked to men who today, on stipple cells, is balm to my have been in an industry where men DUP05 0314394 TREATMENT OF LEAD POISONING . 39 work all day long, with heavy amounts of lead exposure, I note that they rely heavily on the counting of stipple cells. They rely, also, on frequent examina tions, such as have been stressed by Dr. Johns today. There is no machine, protective equip ment, or even an excellent foreman that c,,an always control a situation so that a man may not suddenly have an ex cessive amount of lead absorption. There is the human factor which is un predictable, and that must be controlled by a well founded system of medical control. Nineteen years ago when I was called to become consultant medical director of the storage battery concern where I am now at the home plant, and which has eight or nine plants over the coun try, we had in our home plant 20 men per hundred disabled every year from lead intoxication. We gradually reduced that by trans ferring men, by engineering protection and by conferences with management, who were very anxious for several rea sons to reduce lead exposure. For the past twelve years, we have had no cases of disabling lead absorption or lead intoxication. By disability, agreeing with Dr. Johns, I mean that a man is actually sick. If he has a pain in his belly, constipation, anemia, and a cor responding rising stipple cell curve with evidence of lead absorption shown by lead line and perhaps by lead in the urine, then I believe he is a case of lead poisoning. Until recently, we have had no such case for twelve years. We did have lead absorption but not a case of disabling lead intoxication. We never, in fact, were without some man who had considerable lead absorption as shown by lead line and stippled cell elevation figuring on the criterion of around 20, 30 per 50 fields. This I re gard as the dangerous level. I think, probably, Dr. Johns' figure of 12 is safer; that is, he says 1,200 per million which, when you divide that by 100, gives 12 per 50 fields. There are about 10,000 red cells per 50 fields. 1 think, perhaps, management felt that there was no such thing as lead poison ing or even lead absorption at the home plant for some reason. We had to use respirators at certain jobs. There were certain operations where both the engineers and I had recommended changes, such as remelt ing in the plant where scrap is dumped on the floor and then shoveled into a kettle. But it took a real case to awaken everybody. About a month and one-half ago, I observed that one man was showing stipple cells 20 per 50 fields, when he also began to show a lead line. I re marked on the matter not only to the foreman but to the man himself. I have always found it most advisable to take the worker into my confidence and say, "Joe, you have a lead line. You are ab sorbing some lead. It isn't lead poison ing now, but, if you are not careful and if you do not cooperate with your res pirator, you may have a terrific belly ache." He said he would cooperate, but he didn't. Management wanted to keep him. It was a dirty job; a remelt job is usually the dirtiest place in the factory, and he was willing to work. He was making good money. So, for purposes of production, they kept him. About two weeks ago I wrote, a special comment to the superintendent asking that he be moved. About three days later, he suddenly did not show up for work. His stipple cells were running 20 to 24; and as I said, he had a faint lead line. He was feeling fine the last time I had seen him. The day before he left work, his stipple cells were 50. I took the technician and we went out to see 1 DU P050314395 1 40 DISCUSSION the patient. We had been told by a lay I would call his case a relatively mild man at the plant that probably he case because, usually, these cases do not was out attending to some "special pri come under control for a day or two, vate work," but, having followed the but they do get relief with calcium glu patient personally, I felt he was not a conate intravenously every four hours. I man who would complain unless he believe that is fully as good if not better really had something the matter with than morphine. I agree with Dr. John him. stone on that, again. Knowing the warning signal of that stipple cell count, that sudden rise, 20, 24, 50, I thought, "Here is where our record is broken." When I got out there, I found him sitting up, hunched over, and clutching his abdomen. He was a man who did not complain much. You have to know these individuals to know their reaction to pain. I said, "Joe, how did- you sleep last night?" He said, "I didn't sleep." "What is the trouble?" "My bowels haven't moved for two days. I was up every hour, trying to have my bowels move, but I couldn't do it. I took salts. I took Ex-Lax. I took everything that I or my friends had." His hemoglobin had previously been dropping very slowly, 90, 85, 80--and was now below 80, which is a danger sign---was 78--and his stipple cells were 75. We knew we had some warning; we knew what was coming. The only thing was that I was not tough enough with our management. The other day I read an article by one of the medical directors of a large corporation, and he was describing the qualities of a good medical director. He said, of course, such a physician had to be diligent and a good student, but he had to be a damn good fighter, and I think that is so, even with the best of management. My particular company has really leaned over backwards to give me every cooperation. When I first went there, they said, "Hitch your wagon to a star. We may not be able to gear our pro duction immediately to the changes you want, but we will change as soon as we can," and they have done that consis tently. Our medical program has been keyed into that. So I said, "Well, just get in the car That gives you a practical instance, with us. We are taking you to the though some of you, perhaps, are not hospital." familiar with how the physician works At the hospital we gave the same these problems out, how we study a case treatment that has been outlined, cal and often predict a case and how we de cium gluconate intravenously, to relieve the spasm, and then a saline cathartic, when the spasm was relieved to empty cide that it is a case of lead poisoning, see that compensation is given, and then have the man return to work promptly. the bowels. We also aided that with an This man is not going back to work enema, and we had very good results. with lead immediately. He has no great When we opened the channel, as it were, anemia, however, and I feel that, if con all the different cathartics suddenly be ditions are right, he can do some work gan to work [laughter] and he was very with lead again if properly protected, grateful. [Laughter] We only had to but I certainly would not put him on give the one calcium gluconate intra the remelt kettle again. 1 venously. Thank you. DU P050314396 MONDAY AFTERNOON SESSION November 15, 1948 Ch a ir ma n Bo w d it c h .: Our first speaker this afternoon, as compared with some of those whom we heard this morning, is a relative newcomer to in dustrial medicine. Following periods of private practice and general medicine in the Army, he had his first industrial work in the Plastics Division of the duPont Company at Arlington, New Jersey, and is now medical director of the Electric Storage Battery Company in Philadelphia. Dr. F. B. Lanahan will speak on Preventive Medical Armor for the Lead Industry. PREVENTIVE MEDICAL ARMOR FOR THE LEAD INDUSTRY By F. B. LANAHAN, M.D. Medical Director, Electric Storage Battery Co., Philadelphia, Pa. I should like to preface my prepared presentation by a few remarks which 1 am stimulated to make in light of the tone of the discussions which preceded the luncheon period. My relative youth and brevity of ex perience in industrial medicine prompts me to make the obvious remark, that my position here at this microphone draws heavily on the courage of my convictions. At Philadelphia, the Electric Storage Battery Company has two plants. We have, to our conviction, over 2,000 people who have a lead exposure of some extent. We have two physicians who are full time and two part-time physicians. During this past year, with our pres ent program, grossly revamped from what previously existed, we have cre ated an atmosphere and a facility which have prompted our employees to make easy use of our presence during the eight hours of their day-shift. It is on the basis of that facility, not on the basis of our laboratory studies, that we have seen too many cases of lead intoxication, not severe intoxica tion, yet lead intoxication. They have not come to us commonly on the basis of our stipple cell-hemo globin studies. We are aware of them because these men, to our great good fortune, have made use of our constant presence among them. When we are alarmed by high stipple cells and at tempt to substantiate the lead factor by analytical blood and urine studies, most commonly, we find ourselves in some diagnostic problem other than lead. In passing, briefly, I would like to mention one disorder that impresses us most deeply, and I am sure exists in all of your plants. It is the problem of the Mediterranean type anemia, which we see in a number of our Italians. That, strikingly, will raise stipple counts. The other cases that have come to us primarily through our blood studies have been a multiple myeloma and liver carcinoma. Inasmuch as it takes two full-time physicians and two part-time physicians to give what we feel is a reasonable type of industrial medicine, I would like to join hands with Dr. Gray and say that, with the $2-a-visit type of industrial medicine, you are not getting even $2 worth; it is impossible. 4L DU P 050314397 42 LANAHAN With that preface to describe the en know which horse to look for. When vironment that my presence here repre analytical methods were resorted to, it sents, I should like to present this for was for specific diagnostic purposes; your consideration. indeed, too late with too little for pre Purges are known chiefly within the ventive medical aims. walls of Communistic domination. Ul We found the use of hemoglobin de cerations on the body of nations in terminations, stippled cell counts and flicted by extended arms of the Marxian physical examinations established as the Octopus are excised by healing Chris medical methods of choice, and we fol tian action. Curative or destructive lowed them, lacking knowledge of better are today's searching forces. means. These revealed established dis Curative and constructive are the orders of structure and function. Lead aims of The Electric Storage Battery in air determinations were in use. These Medical Division in Philadelphia. Pre necessarily were brief and infrequent ventive medical principles form the when related to the individual's total foundation of the Division's reorgani work exposure. They could not reflect zation instituted one year ago. Assess negligent working habits. Hygiene in ment of all established procedures was structions fell on torpid health attitudes instituted. On the body of the Pre as on the well known duck's back. The ventive Medical Program, lead control knowledge that these methods and work methods hung like a withered arm, help ing habits were widely existent in the less to prevent illness. lead industry gave small and unwanted Though harsh is our criticism of es consolation. tablished methods, sincere is our ad To establish preventive medical prin miration for investigators who applied ciples a wide chasm appeared before us. these methods in the light of past It was the void between lead exposure knowledge. It is believed these same and toxic lead absorption, between re investigators with their proven abilities sults of spot air samples and actual lead will, with the stronger light of present absorption during the total work period, knowledge, lead the industry forward influenced by 'negligent working habits. into the arena of preventive medicine. It was the darkness obscuring failing As our present control methods are tissue defenses of the worker whose pro known to be common to the lead in longed exposure to generally safe en dustry in general, our convictions and vironment could be causing insidious corrective measures are presented here damage. A bridge was needed to span for general consideration. the chasm and give firm footing for the Entering the field of lead toxicology, preservation of health. we carried deep rooted convictions con Nature is found to give the bridge. cerning the soundness of preventive An instrument of the Divine Scientist, medical principles and the wealth of human metabolism, spans the chasm. benefit they hold for industry. We The man on the j ob is the best impinger looked for methods of control indicative and precipitator of the lead to which he of levels of lead absorption within limits is exposed. His period of collective compatible with health. Methods in use samples represents his total working were found to be non-specific of lead period. His faulty working habits are absorption and demonstrative of exist reflected. These facts are recorded in ing tissue damage. Invariably, the analytical studies of his excretions. horse was out of the barn. Nor did we The direct relationship between at- ! j DUP050314398 PREVENTIVE MEDICAL ARMOR 43 SB ill mospheric and oral lead contamination technical errors. Yet,-it is practical with H and lead excretion in Mood, urine and in the abilities of all of us who are de feces has been revealed by the meticu termined to strive for the highest plane t lous studies of Dr. Robert Kehoe and of medicine and hygiene. his associates at the Kettering Labora It is our purpose to use this method tory. Ranges of excretions related to for the regular observation of our work casual and to occupational exposures men. Relying generally on spot urine and compatible with health have been samples, we will study larger volumes indicated by them. Criteria for dealing or frequent spot samples of urine in the with workmen on the planes of their event a single spot result suggests an lead absorption and excretion have been increasing range of excretion. When established by them on the basis of long high range of excretion is indicated by experience. the additional studies, samples of blood The use of these analytical studies and urine will be obtained for more are known to all of us. Essentially, our precise analysis. application of them has been for diag As the rapid method is known to con nostic purposes. When we have been fuse bismuth with lead, it will be routine alarmed by anemia, high stipple count to inquire of any medication being taken or clinical evidences of disorders which by the workers. The incidence of bis could mean lead intoxication, we have muth in the routine studies is expected resorted to them. to be small. When high values are ob Few of us have applied the analytical tained, the longer method of analysis measures as preventive controls. Known will be employed, thus excluding bis outstanding exceptions have been the muth or any other metal than lead. programs developed by Dr. Hamlin in To minimize contamination of the the American Brake Shoe Corp. and in samples by work clothing it is planned the Ethyl Corp., but to a lesser degree in to collect the samples before work certain other industries, by Dr. Kehoe. clothes are worn or after showers. Col The majority of us have placed the bur lection of samples at the beginning of a den of our negligence on the complexity shift is likely to exclude high concentra of analytical procedures. tions or dilutions of the samples. We can no longer afford to retain our Equipment necessary to apply the use present methods in the guise of lead of the rapid method is approximated to control. We must recognize them for cost $3,000. As the analyses must be their inadequacy as preventive measures made in an atmosphere free of lead, the and resort to them in their true function cost of air conditioning a room in the as secondary diagnostic tools. This production area would have to be ac change is forced upon us by the present counted. A 500 sq. ft. area is considered availability of a simplified, rapid ana adequate for the analytical laboratory. lytical method to determine lead in urine A technician working under the super spot samples. This is the procedure de vision of a chemist can make 30 to 40 scribed by Dr. Jacob Cholak and his determinations daily. To avoid phos associates at the Kettering Laboratory in phate precipitation, the samples must be the January, 1948 number of the Jour analyzed as soon as possible after they nal of Industrial Hygiene and Toxi are voided and always within 24 hours. cology. A general survey of the plant by this Though rapid, the method demands method will establish the mean excretory studied care to avoid contamination and levels of the men working in specific i DU P050314399 44 DISCUSSION areas. On this basis a schedule of inter val studies can be established. Attending to necessary precision, the ease with which the analyses can be made will allow for a flexibility of the scheduled studies to check variations in production methods and environmental factors. This routine applicable to group studies will be applied to individual workmen whose excretory levels fail to conform to mean group values. Air analyses will be used to accom plish its present purpose but it will gain a firmer footing of usefulness in dis tinguishing the atmospheric factor of contamination in suspected environ ments. The suspicion will have been cast by high mean values among the work men of the particular area. Should our facilities and the person nel permit us to develop our own analy ses by the longer methods, as has been shown to be practical by Dr. Hamlin and Mr. Weber of the American Brake Shoe Corp., the combined equipment is judged to cost about $10,000. As in the general field of industrial medicine, small plants with limited bud gets can share the benefit of this quality of medicine and hygiene by pooling their needs and spreading their expenses through the use of centrally located in dustrial clinics. The qualification of such existing clinics for our particular need or the stimulus to develop them is a fertile field of activity for the Lead In dustries Association. As we progress toward the accomplish ment of our program we do so with the stimulating conviction that our efforts will establish a regimen of preventive medical control which will -- Keep men fit for their jobs and jobs fit for men. Ch a ir ma n Bo w d it c h : The principal discussion of Dr. Lanahan's paper will be by a man from whom you heard this morning. He is a specialist in industrial medicine and toxicology of many years' standing, a member of the Committee on Lead Poisoning of the American Public Health Association, associate pro fessor of medicine at Marquette Uni versity and consultant to Globe-Union, Inc. and to a number of other industries and insurance companies. Dr. Elston L. Belknap. DISCUSSION Dr . El s t o n L. Be l k n a p [GlobeUnion, Inc., Milwaukee, Wis.]: Mr. Bowditch, members of the Lead Indus tries Association, friends and co-workers: I believe that Dr. Lanahan is to be congratulated for his convictions and his determination to approach this in a very basic way. 1 wonder, and perhaps he can answer me shortly, whether his method of urine examination, spot samples and group samples, will replace the time-honored method of physical examinations for lead lines, blood studies for hemoglobin, types of red cells, stipple cells and his tory, or whether it is used to supple ment it. 1 am interested to know how soon, also, he thought he could recheck his workers with this method. For instance, if he has 2,000 workers and 40 can be done a day, it would take about fifty days before he could get back and re check a worker. Perhaps he will supple ment that with the other usual forms of treatment in the meantime. My experience with lead in the urine has been to get it, if possible, about twice a year on a lead worker, prefer ably a twenty-four hour urine that has been coEected at home, away from the plant. It is then studied by the Fairhall modification of the chromate method, which, though it takes three or four PREVENTIVE MEDICAL ARMOR 45 days, we have felt from experience has been the most fundamentally safe pro cedure because it is primarily an ana lytical chemical method. I understand that Dr. Fairhall has modified this so that the analysis can be done in a matter of hours. This, I be lieve, will answer the objections to this method. It seems to me the question comes back to this. When you have done an examination of lead in the urine, what do you have? Do you have a diagnosis of lead poisoning or do you have a diagnosis of lead absorption? Certainly, the Public Health Commit tee, of which Dr. Kehoe is chairman, specifically said that no one laboratory finding made the diagnosis of lead poi soning and, as already has been brought out here by a number of speakers, in cluding Dr. Mayers, whom I have al ways admired primarily for her ability as a clinician, that one must view the patient as a whole. No one should at tempt to make a diagnosis of lead poi soning by any one laboratory finding. I have seen workmen who have be come ill with relatively low urine leads. The man that I mentioned this morn ing, for instance, I believe had about --0.25 mg. of lead with no symptoms, and the day he got in the hospital, he had 0.14 mg. of lead per litre of urine. I do not believe that that was the result of any magical treatment that he re ceived in that interval. I think that is simply the variation in urine findings that one must expect in these cases. On the other hand, I have seen men working for thirty years in the storage battery industry with urine values as high as 0.5, 0.6 and 1.0 mg. of lead per litre of urine, who have never been disabled, ill, lost any time and have shown no anemia, who have had no wristdrop, no lead encephalopathy. They have normal blood pressure and a nor mal routine urine. One such man is still turning out a good day's work at the age of sixty-five, and he dales back to the time when conditions were not as we would desire them, when 25 years ago, 75 percent of the men had evidence of heavy lead absorption. We know also that our lead in the air at times is much more than it should be, 3, 10, 12, 15, 18 mg. per 10 cu. feet. Of course, we have corrected that now with air line respirators using as much suction at the source of the dust as possible. In modern production meth ods, even when you are improving a situation, often the worker has to use the respirator. Of course, no one can deny if the respirator is used continuously and no effort is made to correct conditions of lead exposure, it is a confession of en gineering weakness. If you wish, how ever, to keep men from being sick, I am afraid you are going to use respirators occasionally in the storage battery in dustry while protective suction equip ment is being fitted into production. In fact, if that man I was talking about this morning, could have a job found for hijn, and I think it can be found, where he is using not an ordi nary respirator which he is likely to discard, perhaps, because he does not get enough air through it, and is given an air-line respirator, that would be just the same to me as if he were moved out from the lead exposure. I have done that again and again, and the man is still making good money and he is satis fied; the company is satisfied, because he goes on and continues his convales cence even while working. We covered this morning, I think, what constitutes lead poisoning or true lead intoxication. Lead absorption is one thing; disabling lead intoxication is another. We are not using those terms to escape any responsibility. We are DUP050314401 46 DISCUSSION simply wanting to be precise, as we like to be in any field of medicine. A sign of lead absorption, certainly, is lead line, a finding which can be easily determined by spot illumination, even a flashlight, or better still, a head mirror and a small hand Lens which costs about ninety-five cents, inciden tally. One can then definitely say there is or there is not a deposit of linear or round row of dots in the gum tissue next to the teeth. Of course, one should know that the individual has not been taking bismuth for the treatment of syphilis. Otherwise, the physician cannot rule out the fact that the apparent lead line may be a bismuth line. I have seen some per fectly marvelous lead lines that excited me and then I found out when the Wasserman report came back, and after a little private conference with the indi vidual, that he was getting bismuth as treatment for syphilis. In fact, some of the men doing syphilology insist that a patient is not receiving sufficient bis muth unless he shows a bismuth line. One does not always see a lead line if a man has good teeth. A case that I had had perfect teeth and showed no lead line until after he was disabled. The pyorrhea, decay and detritus around teeth seem to be a precipitate of what is apparently lead sulfide in the gum. However, that is merely an evidence of lead absorption. Certainly, if there is no bismuth to be confused with, and if one sees a lead line, one knows that the worker has had too much lead absorption and the phy sician should be on his guard regarding a possible disabling lead intoxication. That is fully as important to me as the determination of the lead value in the urine. It is certainly a good deal less expensive. In doing medical work in industry, one has to learn to fit in with produc tion schedules. The men are not always anxious to come in for periodic re examinations even though it may be on company time, and the company is not too anxious to have them. However, I want to see the men as often as nec essary. That may be every day in some cases, though usually every two weeks and in some cases every month or three months, depending on the concentration of exposure. But to make an examina tion of the man for a lead line, to talk to him, really to get that patient-doctor relationship that Dr. Johns spoke about this morning, to take his blood pressure and to make a note and record the facts is usually a matter of only a very few minutes. Then, if one's technician is working at the same time on another group of men and gets the hemoglobin and the stippled cells, one can fit, as you see, right into production. Nobody warms the chair very long. But we have our information, and we see the man as often as we need to in our best judgment. We have men who have been having their cars stuck for blood every two weeks, for twenty years, and, if we miss them, we hear,from them. If we forget to call them in, they come in complain ing, "Why don't you call me in?" That is something you would not ex pect, but those old-timers know the con ditions that were there before we started this system, and they know that it pays to have this medical observation. So much for lead line, which is a simple procedure and which I should like to illustrate presently. Like a lead line, a few stippled cells, say, 5 to 10 per 50 fields, are also an indication of lead absorption but are not likely to mean lead intoxication. They are much simpler to study than lead in the urine. Lead in the urine is extremely valuable in mass group stu dies. It is valuable for research pur- PREVENTIVE MEDICAL ARMOR 47 poses and, certainly for medico-legal patient, "Yes, I work with lead." cases for doubtful cases. "What do you mean you work with I hope I have intimated that I have lead?" nD quarrel with people who are inter "I work with paint." ested in doing lead in the urine. I think "What kind of paint?" that it is a valuable and helpful adjunct, "I don't know. All paint has lead, f but as Dr. Fairhall has said, urinary hasn't it?" lead excretion is orje of six cardinal Unfortunately, the doctor does not factors in the diagnosis of lead poison always pursue that type of questioning ing and, standing by itself, a urinary until he is forced to on the witness lead indicates nothing but lead absorp stand, and then it is somewhat embar tion. rassing to him as a physician to admit I should like to emphasize the symp his error in being led astray by his toms of lead intoxication. As I said this patient. morning, if a man is sick, if he is really In our State, our Industrial Commis ill, if he is weak, if he is nauseated and sion examiners are often called on to act .V -1 vomiting, and if he has a real constipa as attorney for an applicant, and I have tion or occasionally if he has diarrhea, heard them go through that questioning I and even more rarely, if he has a fleet before a hearing comes to pass. If the U ing arthralgia, or joint pains, with all applicant cannot answer intelligently, the other factors, if we know that he has they say, "You have no case. Go find been exposed to lead, if he shows evi out what kind of paint you are working dence of lead absorption in some one with." of those ways, with those symptoms, If the doctor has the facts he should plus a rising stippled cell curve, then we speak with authority but the average know that he probably has true lead doctor does not realize that he is re poisoning. Then it is just and wise to garded by a layman as an authority. admit it to the patient promptly and tell One of our problems is to make the him what he has and see that he gets average physician realize the weight that immediate relief. Fortunately, relief can is put upon his words. A patient often be given to the most severe type of comes to him and says, "Doctor, I have violent lead colic in 20 to 30 minutes been working .with lead, and I have a after the injection of calcium gluconate. bellyache. Don't you think I have lead I am especially interested in trying poisoning?" to make this clear to you today because The physician often replies, "Well, this i3 what I try to make clear to . my I don't know; perhaps you have," and medical students and what we also try then passes it off. He does not even to make clear to the doctors in . our think of the possibility of this going to county and state medical societies. The court. He finds a little anemia, with or doctors are the harder problem, inci without stippled cells; he may not even dentally. We make the distinction be look for lead line and probably forgets tween lead absorption and lead intoxi to have a urine lead. Then suddenly he cation, because, in a perfectly sincere finds himself called up to a court hear manner, the average doctor who, per ing and he has to make good the mis haps, has seen one or two cases of lead taken idea the patient had, that his absorption and intoxication in his life, physician thought he had lead poison if any, even in medical school, often ing. Such a physician is in for a bad relies primarily on the statement of his half-hour on the stand, with a competent ! DUP050314403 48 DISCUSSION cross-examination by an experienced at torney. The physician, if he wishes to speak with authority, must make his diagnosis one that will stand up not only in court but that he could get up and argue for before his county medical society. There is the jury of his true peers, and every word he says to them has to stand the severest kind of scrutiny. Even though he knows that he cannot make a diagno sis on one laboratory finding alone, he must depend on exposure, plus the fol lowing facts: There must be evidence of lead ab sorption shown in the urine and gums or a few stippled ceils. There must be actual signs of intoxication, usually a disabling colic and usually terrific con stipation, obstipation, we call it, which does not respond to any cathartic. That makes up the ordinary kind of lead intoxication. Ninety per cent of the cases are lead colic. Hunter, of England, has said that there are ten times as many lead colic cases as lead palsy cases. Most of us see very few lead palsy cases, fortunately. I have seen, perhaps, half a dozen in twentyfive years. When we have looked at this thing from the point of view of industrial exposure, then we have to go at it from the standpoint of differential diagnosis. Does this man have a gallbladder colic? Does he even have a coronary occlusion referred pain to the abdomen? Does he have a pancreatitis? Does he have kidney colic? And, in the case of a palsy case, are we dealing with, perhaps, an alcoholic, or infectious neuritis? It is a helpful sign that with most cases of lead palsy, there is no pain, and the palsy is primarily extensor rather than flexor. I have gone into some detail on this because the usual physician has not had experience with this type of industrial exposure. By and large, by his own ad mission, the average doctor knows very little about it except what he reads in the textbooks. These, in many cases, are perhaps twenty years behind the times. The problem, then is one of educa tion of our young physicians as well as education of the laymen, of management and of the worker to distinguish the points I have been making. In regard to residuals, in my expe rience, the 90 percent of the cases which go to make up lead colic come through without any permanent residual. True, they may have temporary anemia. The lead palsy cases may have a residual, but not always, if treated properly. Lead encephalopathies, the third and rarest of the three types of lead intoxi cation, may have a serious residual, if they recover at all, such as mental in volvement, but, again, they may come through, as did some of the ethyl-fluid cases, without any residuals at all. I would not like to leave anybody with the impression that we do not meet lead poisoning anymore in modem in dustry. 1 agree with Dr. Johnstone, that in the small industry we are likely to have it all the time. It frequently ap pears in unusual places in many small plants. The accompanying photographs show how we go in what we think is a 1, 2, 3 manner. Fig. 1 -- I show this photograph of inserting separators between storage battery plates because I think any lay man who has never done anything with lead -- and the average doctor has to be regarded as a layman in this area -- can tell, by looking at the left-hand picture, that conditions in that picture are not nearly as good as they are in the righthand picture. You can see in the picture on the lefthand side that a plank has been thrown on the floor; lead dust can fall on the DUP050314404 PREVENTIVE MEDICAL ARMOR 49 Fig. 1--The old and new method of inserting separators between storage battery plates. plank and be kicked up and inhaled. In the right-hand picture there is a slotted rack so the dust falls through to the floor where it will not be kicked up as dust and then can be washed down at the end of the working day. In the right-hand picture again we have slotted down-draft suction tables. I think you can see for yourself that that man on the right has a much safer job. In spite of that, we insist that they wear respirators, whenever possible, though, practically, the engineering pre cautions there have cut the lead ex posure remarkably. Fig. 2 -- Often we have the problem as to diagnosis of a lead line. "Doctor, have you ever seen one?" Some doctors admit that they have not, but I think this picture proves that there is such a thing. You see here the definite, punctate deposit of lead sulphide in the mucous membrane next to the teeth. The dirt and detritus on the tooth is not the lead line. That is what we see under a lens, a ninety-five-cent lens, plus a flash light. Thus, one can make the diagnosis in the home. If there is no bismuth treat ment here, the case is one of heavy lead absorption. Fig. 3 -- We heard a good deal about this mythical character called "Mr. Stippled Cell" this morning. There is one. This is a white cell; these are red cells. There is another stippled cell. There are two stippled cells in one field, so that 50 fields would have about 100 DUP050314405 50 DISCUSSION Fig. 2--The definite, punc tate deposit of lead sulphide, appearing as small black dots, in the mucous mem brane next to the teeth. stippled cells which is quite enough number of teeth opposite which there often to be associated with disabling is a gum lead line, and the strength of lead colic. the wrist extension. We observe the Figs. 4 and 5 -- This periodic re blood pressure finding also because we t examination chart gives you an idea of are interested in finding whether these i the value of recheck studies. These ex cases are going to go on and develop t aminations are made about every two an increased amount of hypertension weeks with the date at the top; then at and arteriosclerosis as some have al the side the particular symptoms that we leged in the older literature. To date are looking for, either weakness, head we have not seen that in our experience. ache, drowsiness, if there was a brain At the bottom of the chart we have involvement and the usual gastro-intes- a place to record stippled cell count tinal symptoms, such as constipation or colic. We do watch the weight though the weight does not give any specific in formation, only to indicate something as to the general physical condition of the man. Then we test each man for extensor weakness of the wrist at the same time we are taking his blood pressure and looking at his teeth. Teleky, I think, was the one who brought out most clearly the importance of testing the extensors prophylactically. We make a note as to the pallor, the Fig. 3--Photomicrograph showing stippled blood cells. ! i DUP050314406 PREVENTIVE MEDICAL ARMOR SI HISTORY 1. NAME . 2. STUDY NO. BIRTHPLACE 3. ADDRESS 4. M. F. W. B, S. M. W. D. 5. FAMILY DR. 6. WHAT TYPE .WORK APPLIED FOR: 7. HISTORY OF PREVIOUS EMPLOYMENT IN THIS PLANT: CLOCK NO. DESCENT PHONE L.R. AVER. WT. WT. 1 YR. AGO 8. HISTORY OF PREVIOUS EMPLOYMENT IN OTHER PLANTS; DATE AGE GREATEST WT. 9. FAMILY HISTORY GOITER - HEART BRIGHTS TBC. _________ DIABETES______________________ 70. PAST HISTORY: _________________________ _________ ILLNESS {SCARLET - RHEUMATIC FEVER) _________ OPERATIONS__________________________ _________ ACCIDENTS _______________________ VENEREAL TREATMENT _________ REMARKS: ..... ........................................ H. PHYSICAL EXAMINATION: PRE-EMPLOYMENT DATE WEIGHT HEIGHT EST. WT. PULSE TEMPERATURE PALLOR LEAD LINE is OF TEETH R. WRIST EXTENSION 1. WRIST EXTENSION ! LUNGS GLANDS I ARTERIES I B. P. HEART ABDOMEN REFLEXES HERNIA SPINE EXTREMITIES VISION-R. L VACCINATION B. H. EXP. 12. LABORATORY EXAMINATION: STIPPLING # IN 50 FIELDS HGB. <SAHLI) R. B.C. W. B. C. URINE WASSERMAN 13. DIAGNOSIS: UPON DISCHARGE 14. RECOMMENDATION: Fig. 4--Periodic re-examination chart (front). DUP050314407 52 DISCUSSION Form 804 PERIODIC RE-EXAMINATION NAME Number DATE OCCUPATION DURATION PREV. PO. EXPOS. HISTORY WEAKNESS DROWSINESS INSOMNIA HEADACHE VERTIGO i 1--------- -- ! BOWELS # TIMES WITHOUT CATH. ; CONSTIPATION DIARRHEA |.; S'- METALLIC TASTE ANOREXIA NAUSEA ! 1I 1 VOMITING ABDOMINAL OR CHEST PAIN WHERE WHEN WT. AVERAGE RESP. ----- ------ [! j I---------- !----- ------------ J-- j MUSCLE WEAKNESS MUSCLE TREMOR 1| r h| MUSCLE TINGLING MUSCLE CRAMPS 1 1i 1 : | --------------- 1-------------------- JOINT PAINS i1! ACUTE ILLNESS PHYSICAL EXAMINATION PULSE - TEMPERATURE PAtlOR LEAD UNE # OF TEETH R. WRIST EXTENSION j :1 ..... . T" i : i ' I---------------- ii !i 1' I1 ; ........... i L. WRIST EXTENSION LUNGS i GLANDS B.P. HEART ABDOMEN REFLEXES HERNIA | SPINE EXTREMITIES j -- LABORATORY EXAMINATION STIPPLING # IN 50 FIELDS HGB. (SAHII) R. B. C. w. a. c. URINE WAS5ERMAN i 7 | | | r e c o mme n d a t io n o r r x ` Fig. 5--Periodic re-examination chart (back). DUP050314408 PREVENTIVE MEDICAL ARMOR 53 and the hemoglobin. In one particular statement that there is no short cut to case, early in the game, when we did clinical medicine. As Dr. Mayers has not take warning quick enough, he said, every single case has to be viewed was running 10, 21, 30, 110, 217 stip as a whole, from the viewpoint of gen pled cells and we still let him stay on eral differential diagnosis, and one must the same job. He began with diarrhea, study the whole picture, not any one which was an intestinal influenza, and at laboratory finding, not even stippled first he had no lead line. Then he sud cells alone. denly blew up with constipation and Knowing these things to be facts, we afterwards he had his lead line. can, with good conscience, go about our The anemia was a late development job of keeping the worker healthy and here. That is the most important thing, I at work. think, in the blood picture regarding Ch a ir ma n Bo w d it c h : We are so be lead. We all agree that lead stippling, or hind schedule that I think we had better stippling of red cells is not a specific in confine any further discussion to a brief dicator for lead absorption or intoxica reply by Dr. Lanahan, if he so wishes. tion. You may find it with Hodgkin's Anything more cam be at the end of the disease. Benzol poisoning, tumor, malig afternoon, if we have time. nancy, any type of severe anemia, will Dr . La n a h a n : Dr. Belknap posed sev eventually show nucleated red and stip eral questions in relation to my presen pled cells, but with the lead intoxication, tation. The one that strikes me as most you get your stippled cell rise early, long important is whether or not we plan to before the hemoglobin drops. use urine lead determinations to make In this case he did not have his drop our diagnoses of intoxication, or resort to 65 and 60 hemoglobin until after he to other measures. was disabled. If we had been relying on He has touched on the heart of what the hemoglobin, we would have allowed I feel is our presentation. The problem him to go a lot further than we did, ab of which we are intolerant in our present sorbing even greater amounts of lead. program is that it is a diagnostic pro Following calcium gluconate intra gram. When we apply our proposed venously, the patient went back to work analytical studies as we are determined and worked for two or three years. He to apply them and are faced with a was in excellent physical condition be diagnostic problem, we will admit to fore he left our employ. He went back ourselves that we have failed somewhere to the same type of work, incidentally, along the line, foiled in prevention. but with a respirator. This particular Our persuasion to head in this direc man had been working at a job where tion is based on the studies that have nobody thought he had a lead exposure. been made by Dr. Kehoe and others who He was working in the forming room, have established the ranges of blood and normally a wet room, but he was the one urine lead levels that are compatible man in the department who was drop with health, that are seen in people with ping dry plates into a battery ease. He known occupational exposure, accepting did not show up for examination until these ranges as our starting point. We he got sick. We did not like that; we like hope to keep our people within a range to be able to put our finger on these of lead excretion compatible with such cases of impending intoxication three or standards. As we see them working their four months ahead of time. way above such standards, we hope to I think I should like to close with the make more extensive studies to catch the DUP050314409 54 DISCUSSION bugs in our rapid method. At this stage Our chemist, who at present does our we feel that we will be ahead of clinical lead in air determinations, can oversee symptoms and stipple cell changes. We the precision of our laboratory analyti will be before the stage of diagnostic cal studies, for I do not presume to be procedures, using preventive methods. so qualified. Dr. Belknap has asked, if urine deter 1 might add this. In Fig. I, Dr. minations will replace physical examina Belknap presented to you the picture of tions. As I mentioned in the preface to an assembly line, with grating in the my presentation, in spite of, let's say, floor and the down-draft in the table. \ the abundance of our medical personnel, Men were wearing respirators. we feel that we are not able to watch our It is my routine to accompany the gen people as intimately as necessary to pre eral safety committee which, inciden vent diagnostic problems. tally, is a management-labor coordinated We are looking for something which committee, in visiting every procedure will give us a signpost by which we can throughout both plants once a month. I have our fingers on everyone before would love to find that each time we they become diagnostic problems, and passed the assembly line and any other we hope that onr proposed method is the process we bad, we would see our men measure by which we may accomplish actually wearing respirators, where they this. When we find groups, and the indi have been issued. viduals within the groups, having excre The respirator is either, obviously, tory ranges above those which have been down on his chest or it is in a position declared as compatible with health, we where he can quickly duck his nose will resort to our present program of under it as we are going by. physical examinations and complete We have down-draft; we have water blood studies, repeating them as fre under the grates, and we have respira quently as we wish. tors. Our air levels worry us. We have ! Again, let me say, when we have a people getting sick. We are doing what ! diagnostic problem, we will admit that all of you are doing, and we are not i our preventive medical program has a satisfied with it. f hole in it. Ch a ir ma n Bo w d it c h : This seems an < Dr. Belknap asked how soon we can appropriate moment to repeat Mr. H. J. plan to review these people, if it re Weber's very excellent definition of the quires one technician for 30 or 40 deter industrial respirator. He has aptly de minations daily? Our present program, scribed this device as "A muzzle type which I have described as involving ornament worn loosely pendant from study of stippled cells, hemoglobin deter the neck, used in dirty industries to dis minations and personal communications tinguish the laborers from the office with these people, entails the entire acti employees." vity of two laboratory technicians. I am sorry that we cannot continue We estimate that it takes them 20 this discussion further at this time, for minutes for each technician to do each I know that there are one or two others laboratory study, which results in the who could contribute valuably to it, but determination of the hemoglobin and the we must get on with the program and stippled cell count. We believe urine hope to be able to continue at the end studies will involve no greater time and of the afternoon or, if not, then to will require no additional technical per morrow. sonnel. Our next speaker was the physician DUP050314410 CO-ORDINATION OF MEDICAL SERVICES 55 ol the Massachusetts Division of Occu pational Hygiene from 1940 to 1942 and then became director of the Louisi ana Division of Industrial Hygiene. He went from that position into the Army as a battalion surgeon in the infantry. Then, in 1946, he became physician of the American Smelting & Refining Com pany at Tacoma, Washington, and in 1947 was appointed medical director of that company, with headquarters in Denver, Colorado. Dr. Sherman S. Pinto will discuss The Co-ordination of Industrial Medical Services. THE CO-ORDINATION OF INDUSTRIAL MEDICAL SERVICES By SHERMAN S. PINTO, M.D. Medical Director, American Smelting & Refining Co., Denver, Colo. In a medical program embracing many widely scattered plants it is es sential that careful consideration be given to centralization of some and de centralization of other procedures. In this talk I wish to point out where centralization is advantageous and also where decentralization is preferable. Medical care in industry is more than bandaging cuts, setting fractures and passing out aspirin for headaches. An industrial medical program should be designed to prevent disease, recognize sickness early so that treatment can be started before serious consequences have developed, and help employees secure the best medical care when sickness does occur. Now let us examine the various parts of a medical program to see how they fit into the general picture. The medical examination form is one of the basic tools of industrial medicine and great care should be exercised in its adoption. It is preferable to use the same medi cal examination form throughout one company. This establishes uniformity -of procedure and allows certain aspects of the examination to be stressed. Medical examination forms are ex tremely varied and there is no universal form applicable to all industries. We considered numerous forms used in in dustry, insurance forms. Army forms and hospital forms before we drafted a form for our own use. The form we now use is as simple as we could make it, yet all the essential and important in formation desired can be recorded. It was also designed to allow the doctor to make the examination with a minimum of writing. Most of us dislike to write extensive records and will make better reports if they can be written briefly. At the top of the accompanying form is the usual identifying data, name, ad dress, etc. Immediately below that is a section for recording past occupational history. Most medical schools sadly neg lect the occupational history but we feel it is especially important in the lead industry. We have found a number of men applying for work in lead plants who will state in their occupational his tory that they recently quit work in another lead plant. Obviously such men should be studied very carefully for evi dence of abnormal lead absorption be fore they are put to work and exposed to more lead fumes and dust. In the occupational history we also stress exposure to dust in former jobs. DUP050314411 56 PINTO Many of our plants have ore crushing operations and we have found it im portant to know whether or not a man has been exposed to silica dust on other jobs. We hire men with early silicosis. for instance, but we put them on nondusty work. The usual medical history is recorded in the next space. As you can see, a number of diseases have been- mentioned AMERICAN SMELTING AND REFINING CO. PLANT Fill out this blank IN DUPLICATE and sond carbon copy to office of Medical Director, Shaman S. Pinto, IS. D., BO? First National Bank Building, Denver 2, Colorado. Original to remain in doctor's or narea's die in plant dispensary as b confidential record, available only to plant doctor or none. {Trial ar l>pa SpalliBC <u aa Hoc!*) Samritr cart) JC a W D U. F. OCCCPAHIOHAIi HISTORY (Oar nit asnnri t Cut or too**!}--------. If aa. pn drcnsataaiaa, fnalbB and dalaa.) MEDICAL HtSTOHYi (Any o! loUowtftgr in pail? TUHEEC0Z031S. ASTHMA. REAHT DISEASE. EKEUMAHSM. DIABETES. EPILEPSY, VENEREAL DISEASES. DISEASES DUE TO OCCUPATION. DEBMAT1T1S. AUENGIES. INFUMES. OFQtATIONS. U ao, piv# drcwaatencet. duration and dalaa.) fSa* BuUaUa ol Inilruetiooa lot dalaSa all 1total fcalote). FAOSFECTtVS EHTLOlUir {State aun oeeapattoay OLD EMPLOYEE? {Total yaaob Slate oeoopatUa) msorr c o mp l a in t s * DATS or EXAMINATION DATE OF SUMMATION DATE OF EXAMINATION WnOBT-HEKJHT TEMTE2ATUHE GENERAL APPEARANCE EVES VISION--Sight T 1 OfSdalAKA VISION--Loll f St*CS,>rt* 1 J0~ U Cor- S3 11 -- -- IlCtld -- -- 20 H Cr> M 44 -- -- iadd -- -- ta 20 H ---- 20 U ---- Cor* a ii ractad -- -- Ct 20- II (acted -- -- to 20 l ---- 20 U ---- Cm- 20 li KCtad -- -- lo Car- 20 U ractad -- -- NOSE AND EARS MOUTH THROAT AND NEC* HEART BLOOD PSESSUBE CHEST AND SUNOS ABDOMEN BACK HESttUS AND ROS EdlDOTIEI VAMOOSE YENS AND I, sxnr i i EMOTIONAL STA9IUTT OTKES nNSSiaS KD-S--10-49 Fig* 1---Medical examination chart (front). DUP050314412 CO-ORDINATION OF MEDICAL SERVICES 57 I if by name. This was done to remind the three columns for recording physical I doctor not to overlook those diseases findings. The first column is used for the * which might have sequelae of import initial examination, the other two for l ance for work in industry. subsequent examinations. As you can On the lower part of the sheet are see, all the findings which the doctor (Sm Euliatm o! toctnetioM ta details on all Itatet feakiw) P URINALYSIS g BLOOD SESOLOBT ^ COMPLETE BLOOD COUNT ^ O STIPPLED COUNT 2 3 l e ad in treats " S LEAD IN BLOOD DA7E 07 BUSONATION DATE OF EXAMINATION DATE OF EXAMINATION OTHER LABORATORY CHEST X-RAY FINDDICS SUMMARY OP ALL SiatJtnCAKT FStDOtOS RECOMMENDATIONS WAS PROSPECT HIRED? IP HOT HOED. STATS WKT i| MAY REGULAR EMPLOYEE CONTINUE PRESENT DUTIES 17 NOT, STATS WHY FAMILY PHYSICIAN AND ADDRESS EXAMntSta DOCTOR IPItu* Sign) DISPENSARY RECORD OB C THER MOTES Fig. 2--Medical examination chart (back). DUP050314413 58 PINTO makes are recorded on one side of the form. There is no necessity to turn the form over, and a carbon copy can be easily. made. The reverse side of the form (Fig. 2) is used for recording all types of ex aminations which might be made in a laboratory. Only those spaces are used which are required, and not all that laboratory work is done on each man. Near the bottom of the form are sev eral questions for the doctor to answer. The first question is, "Was prospect hired?" The next question is, "May regular employee continue present du ties?" In essence the answer to these questions represents the doctor's final medical opinion of the man and his rela tion to the job. At the bottom of the form is a space for clinical notes which are made when a man returns to the dispensary for any sort of treatment. Thus, on this one sheet we have a serial record of an em ployee showing his physical examination at three different times and a brief record of his treatments in the dispen sary during that time. Sometimes more space for clinical notes is needed and a blank sheet can be attached to the original one for this purpose. Such a form as I have described is suit able for pre-employment and periodic ex aminations of workers in any type of a smelting plant, and will also serve for keeping clinical records. It is a multipleuse form from which unnecessary exam inations and questions are eliminated. The family history, for instance, has been eliminated since we found such little information of practical value. Similarly, you can see that routine measurement of the size of chest and abdomen have been discarded. These are time consuming procedures which have no particular significance in an industrial medical examination. We also wrote a comprehensive bul letin explaining every item on each line of the examination form. This bulletin is given to all plant physicians so they may understand just what is included in each item. Before a man is hired he is given a thorough physical examination. This is done for the purpose of determining the type of work he is best suited for physically as well as to see that the work he is going to do will not be in jurious to him. Thus, a man with der matitis would not be hired for a job in which he might have excessive ex posure to a skin irritant. In certain plants all jobs go by strict seniority while in others men can be hired for specific jobs. For this reason the de cision as to whether or not a man is qualified for a job must be made by the local doctor. We do not attempt to lay down hard and fast rules for pre employment physical qualifications. Periodic examinations for hourly em ployees are a form of preventive medi cine. Most of our employees are examined every two years and all findings of sig nificance are discussed with the patient The examination itself may include spe cial laboratory work if such seems indi cated provided the cause of the disorder is the result of an industrial process. This includes such things as urinalyses for ar senic, selenium, etc. For special types of examinations which seem necessary for further diagnosis as in cases of early cataract, suspected cancer of the gastro intestinal tract, etc., the patient is referred to his own physician. No man is fired because of a disability but on the phy sician's recommendation he may be al lowed a year's sick leave with retention of seniority rights. Men quickly realize when periodic ex aminations are for their benefit and we have had the experience of men ori a picket line come to the dispensary dur ing a strike and ask for their periodic ft <, DUP050314414 CO-ORDINATION OF MEDICAL SERVICES 59 examinations. They knew the examina munity. Later a type of influenza ap tion was for their benefit and any dis peared protection against which was not ability which might be found would not provided by the vaccine. As a result be used as an excuse for discharge. many employees became sick and were Similarly, we have had a union official antagonistic to the further use of pro with heart trouble ask us if it would be tective vaccines. Preventive medical safe for him to make an extensive air measures must have a reasonable chance ' plane trip at a time he was engaged in to succeed or the whole idea of preven 1 contract negotiations. Such a question tion will be discredited. puts the doctor very much on the spot The chest X-ray has become an im I because if he says the trip should not portant part of the examination pro be made the doctor might be suspected cedure. For plants with 1,000 or more of trying to sabotage the union's part in employees the purchase of an X-ray the negotiations. However, the important machine by the plant is justified. For point is that a medical department can smaller plants, arrangements are made have the respect and confidence of both to have chest plates taken by a local I: union and management if it is scrupu doctor. Labor turn-over is still high in lously fair and honest in its work. many parts of the country so we often The question is often raised whether do not take a routine chest X-ray until r industry should engage in preventive a man has been on the job 30 days. public health medicine. We feel that However, if the man gives a history of when local conditions call for preventive arrested tuberculosis or exposure to sil medical practices, industry should parti ica dust, an X-ray is taken immediately cipate. Plant-sponsored smallpox vacci as part of the pre-employment examina nations at a time when there is a local tion. Abnormal chest films are sent to a smallpox outbreak is an example of the central office for consultation. We feel type of preventive measure I have in only a recognized expert can be ex mind. pected correctly to interpret the evidence The administration of influenza vac of early tuberculosis or pneumoconiosis. cine is another measure about which By the same token many men are ap there is controversy at present. During proved for employment who have healed the last two years influenza outbreaks chest lesions of what was probably a have been local in nature and the type fungus infection of the lungs. We are of infecting organism has varied in dif interested in trying to put a man to ferent communities. Such outbreaks have work. That should be the aim of a also varied as to time of appearance in medical examination, not to try and various parts of the country. We have keep men from working. asked our individual plants to watch In a company-wide medical program closely for the appearance of influenza practices which are found beneficial in in the community. If a type of influenza one plant can be extended to all plants. appears for which a suitable vaccine is When doctors know they are part of a available we recommend that the local company-wide plan, they become more plant make an effort to vaccinate as interested in the workings of the plant. many of its employees as possible. This We encourage all our doctors to visit the is done at Company expense. Two years various departments of their plant fre ago some of our plants pushed the ad quently and become familiar with all ministration of influenza vaccine before operating procedures. Only when a doc any influenza had appeared in the com tor understands a man's job can he cor- DUP05Q314415 60 PINTO rectly evaluate the presence or absence of the health hazards connected with that job. In the central office, we keep in close touch with company management and are acquainted with new develop ments and processes which are to be in stalled in plants. Having in mind the potential hazards of a new process we are able to visit the doctor at the plant concerned and acquaint him with the new process at the time it is started. Many times this has proven the truth of the old axiom that "an ounce of pre vention is worth a pound of cure." Medicine in general and industrial medicine in particular is entering a new era. Whereas the disease process of the individual patient has been of primary concern in the past, we are now intensely interested in the environment and its possible effect on the patient. The atom bomb has made us all acutely aware that the environment can suddenly and violently affect the health of an indi vidual. Modern industry has changed remarkably in the last 15 years and almost all industries use many more toxic chemicals now than were em ployed formerly. Thus in a more wide spread but less dramatic fashion the modern industrial physician is as con cerned with the environment as is the doctor surveying the effects of an atomic explosion on the general population. Our studies of the plant environment are centralized rather than left to the individual endeavors of each separate plant. At a central laboratory are men trained in industrial hygiene -- trained to make all the necessary air studies for fume and dust control. They are equipped with all the necessary instru ments, and this expense is justified since they use these instruments the year around. Check surveys are made in each plant at least once a year, and all op erations producing questionable amounts of fume or dust are studied. An im portant part of such studies is to dif ferentiate between conditions which are a nuisance and those which are a definite health hazard. In the control of poor conditions a higher priority is naturally given to the control of definite health hazards than to the nuisance conditions. A program of periodic urinalyses has been adopted as another measure of the effectiveness of engineering control in the manufacturing process. With regard to lead, all men potentially exposed to lead dust or fumes have a routine urin alysis for lead at periodic intervals. Urine samples are collected at the indi vidual plants and sent to the central laboratory for analysis. The samples are collected in glass bottles which have paraffin-lined caps and aTe shipped in wooden containers. This has proven very satisfactory and we have much confidence in the urinary lead deter mination which is done routinely by a skilled chemist. Urinary lead analyses done infrequently by a chemist are often subject to error, and we feel that centralizing the urinary lead determina tions results in much greater accuracy. For emergency determinations a sample can be airmailed from any part of the United States on one day and the result telegraphed to the sender within 24 hours. Ordinarily, routine samples are sent by train. The centralization of the industrial hygiene laboratory also allows the chem ists there to become proficient in ana lyzing urine for the rarer non-ferrous metals. The need for such determina tions in any one plant is infrequent but the aggregate from a number of plants provides a sufficient number of samples to assure a chemist maintaining his skill in running that determination. All individual urinary lead determina tions are recorded in the central medical office on graphic record cards as shown in Fig. 3. By this means, a continuous i DUP050314416 CO-ORDINATION OF MEDICAL SERVICES 61 'I AMERICAN SMELTING AND REFINING COMPANY URINARY LEAD CONCENTRATION PLANT ____ 62 PINTO visual record is easily kept. If a man's brains of the executive group is a com urinary lead level reaches an unfavorable pany's greatest single asset, and it is height or starts to show an unfavorable important that the health of these men upward trend, the plant manager's atten. be properly protected. We have a sys tion is called to the case and steps are tem of annual examinations for the ex taken to reduce the man's lead exposure. ecutive group which includes a chest As a point of interest, I should like to X-ray and an electrocardiogram. The point out that urinary lead analyses occa examinations are made by a doctor of sionally bring to light unexpected lead the man's own choosing, and copies of \f exposures. One such case that we saw the examination are sent to the central recently was in the operator of a plant medical office. These records are strictly vacuum cleaner. Apparently the cleaner confidential at all times. Since execu bag leaked slightly and the operator tives are sometimes moved from one absorbed enough lead dust from this plant to another, it was found ad leak to show an excessive exposure. vantageous to file their records in a The graphic record cards are useful central office. Thus, these records are in following the individual employee easily available if a man wishes to have and may also furnish other information. his old records compared with more re The records of the same department in cent ones. If the examination discloses several plants can be easily compared a physical condition which should be and the effectiveness of control measures corrected, the executive is contacted and in different plants brought out. Similar urged to get the necessary treatment. ly, different departments in the same The cooperation of the executive group fj. plant can quickly be compared and the has been splendid and the vast majority place where further engineering control have expressed their appreciation of is necessary becomes quite evident. such examinations. New construction and new processes The last point I would like to men are of interest to the medical department tion is the medical care of non-industrial because we feel it is much simpler and illnesses. This is a subject about which less expensive to build proper controls there is much discussion at present, and into new construction than it is to add I anticipate more in the future. them later. This acquaintanceship with Prepaid medical care plans are nu new construction is primarily a problem merous in type and complexity, and for the medical director since he is in local workman's benefit associations, closer touch with company operations. commercial insurance plans, and Blue Several engineers specialize in ventila Cross are familiar to all of you I am tion and wc work in close cooperation sure. These plans have been devised with them. When a new installation is because there was a demand for them. completed we make atmospheric tests In- addition, the idea of compensation for fume and dust control. If a ventila for time-loss due to accidents is almost f| tion job is effective and satisfactory, it universally accepted in American indus will probably be used as an example in try. As a further extension and broaden later installations so we work with the ing of these two ideas, sickness benefit engineers to make each new type of unemployment insurance is being advo equipment as satisfactory as possible. cated in many states. At present two An important part of any medical states have such insurance in force and program is the development of periodic in a third it was started in January, examinations for top executives. The 1949. 1 DUP050314418 CO-ORDINATION OF MEDICAL SERVICES 63 This type of legislation affects indus trial medical practice particularly if there is a difference between the amount paid for accident benefits and sickness benefits. Thus an employee with a low back pain of rather vague origin will wish to have his disability classified under the fund which will pay him the greatest benefit. It is important, then, that such legislation be carefully studied when it is proposed and suggestions made to keep accident and sickness bene fits comparable. Furthermore, there should be no duplication of payments from both accident and sickness funds for the same disability. Such duplica tion places a premium on accidents and defeats the purpose of the legislation. Ch a ir ma n Bo w d it c h : I am afraid that, for lack of time, we will have to continue to the next subject without dis cussion of this one. Our next speaker is, again, one of the younger group, a man whose principal interest, until recently, has been in the field of biochemical and physiological research. For the last year and a half he has been senior industrial hygiene physician of the New York State Depart ment of Labor. Dr. John E. Silson will discuss Med ical Control of Lead Workers -- A State Viewpoint. MEDICAL CONTROL OF LEAD WORKERS -- A STATE VIEWPOINT By JOHN E. SILSON, M.D. Senior Industrial Hygiene Physician, New York State Department of Labor, New York Lead poisoning is one of the oldest and best known of the industrial dis eases, and for this reason was one of the first problems to confront the various governmental industrial hygiene agen cies. Today, after many years of experi ence, countless statistics and innumerable studies, its control still remains one of the principal tasks of the industrial hy gienist. The Division of Industrial Hy giene and Safety Standards of the New York State Department of Labor, like its counterparts in other states, is con stantly made aware of instances of ex posure of workers to excessive amounts of lead. Through the years, many prin ciples of control have been evolved which are applicable to some of these cases; but others may present problems requiring a new approach and an indi vidual solution. This paper will present certain aspects of both the standardized procedures which the Division has evolved and the special problems which it has met. New York State has always been in the forefront in the field of labor legis lation. Similarly, it has pioneered the entrance of the states into industrial hy giene activities. The State Labor Law provides for protection of employees from "dust, gases, fumes, vapors, fibers or other impurities .... generated or released in the course of business car ried on in any workroom or factory in quantities tending to injure the health." Under this provision, the control of lead fumes and dusts has been made the responsibility of the Division of Indus trial Hygiene and Safety Standards. There are further provisions in the La bor Law specifically applicable to lead; one which forbids taking food into any workroom where lead is handled, and requires the employer to provide a suit able eating place; and another which requires that the employer supply hot water, soap and towels to all employees exposed to lead. All cases of lead poison ing must be reported to the Labor De partment. To carry out these and other provi sions of the Labor Law, the Division of Industrial Hygiene has been established as a part of the Labor Department. In this respect it differs from most other states, where industrial hygiene is a function of the Health Department. This enables the Division to integrate its work closely with the other units of the Department responsible for protecting the workers. Codes for the safe opera tion of factories and other industries are drawn up by a special unit of this Divi sion. The enforcement of these Codes is facilitated by cooperation between this Division and the Division of Industrial Safety Service. All equipment for the control of atmospheric contaminants must be approved prior to installation by the Industrial Hygiene Engineering Unit; and plans for all factory and mer cantile buildings outside New York City must have the approval of another En gineering Unit. This results in informa tion as to hazardous operations coming to our attention at the onset and cur rently from such sources as the factory inspectors and the Workmen's Compen sation Board. Tied into all these activities are the functions of the Medical Unit. It inves tigates cases of industrial disease to advise on prevention and control, con ducts field research in various poten tially hazardous industries, organizes 64 DUP050314420 MEDICAL CONTROL 65 programs of medical control where work ers are exposed to toxic substances, and assists outside physicians in the dif ferential diagnosis of cases of doubtful industrial poisoning. It has also been of assistance in helping plants set up med ical offices, and in planning special hy giene facilities for factories with par ticularly hazardous exposures, it has on its staff an industrial nurse consultant conversant with the problems of running a plant medical office, and a nutritionist experienced in organizing and improving plant cafeterias, lunch rooms and other eating facilities. In carrying out these activities in plants where an exposure to lead exists, we have observed a wide disparity in the nature and extent of medical supervision of the exposed workers. In some plants, almost complete reliance is placed upon stipple cell counts; in others, urine ex aminations for lead concentrations alone are employed. Still other plants are either unaware of their hazard, or do nothing about it for other reasons. Even where fairly complete examinations are made, considerable variation in the in terpretation of results has been found. MEDICAL CONTROL PROGRAM In the interest of promoting good in dustrial hygiene, and of spotting cases of lead absorption before poisoning oc curs, the Division has drawn up a pro gram for the systematized periodic survey of workers in plants handling lead in any of its forms. The recom mendations embodied in this program are the minimum controls which should he maintained in order to insure the health of the workers. They are predi cated on the realization that laboratory tests and mechanical analysis cannot supplant the intelligent observation and evaluation of the worker as an individual by a properly qualified physician. On the other hand, it is appreciated that the average plant physician cannot do un limited numbers of complete physical examinations. This plan is designed, therefore, to assist the physician in de tecting early cases of increased lead ab sorption or intoxication by screening all the workers at frequent intervals. In a plant with a limited number of lead workers, this screening could be easily handled by the plant physician himself. Where larger numbers of em ployees are involved, however, the fre quent screening examination might be done more conveniently by the plant nurse or medical technician, leaving the physician more time to evaluate the re sults and to call in those workers with abnormal findings for additional exam inations. This would require an indi vidual specially trained in hematological technique who would be given supple mentary instruction by the physician on what to observe in the screening exam ination and on the proper method of collecting urine samples to avoid con tamination. Such lay personnel, how ever, should be carefully supervised by the physician in charge. CLASSIFICATION OF WORKERS The program is designed to cover all workers handling lead in a plant or those performing special functions which bring them into contact with lead in any form, whether as fumes, dusts, mists or vapors. Variations will undoubtedly be necessary depending upon the number and percentage of workers in a plant who are exposed Lo lead, and the extent of their exposure. In general, particu larly in those plants where the majority of the workers are so exposed, it has been found advisable to divide the workers into two groups. Group A, the high exposure group, should consist of all workers directly exposed to large amounts of lead or lead compound dusts, fumes, and mists, such as burners. DU PO50314421 68 SILSON oxide makers, pasters and dry-plate handlers in battery plants; pigment grinders, blenders and baggers; paint mixers and sprayers; smelters and cast ers in lead, brass and other alloy foun dries; and all other workers, including porters and maintenance men, whose occupation involves exposure to high at mospheric lead concentrations. Group B, the low exposure group, should in clude the less exposed workers in plants handling lead or lead compounds, such as shippers; wet-plate battery assem blers; all workers in typesetting and casting rooms of printing plants; work ers engaged in wet processing of lead, and all other workers whose occupations involve exposure to relatively, lower at mospheric lead concentrations. SCREENING EXAMINATION The program is based on a periodic screening examination of all the employ ees. The physician, plant nurse or med ical technician should interview each worker in Group A monthly, and in Group B every two months. The worker should be observed for pallor, tremor and lead line, and questioned for the fol lowing symptoms: weakness, headache, vertigo, fatigue, insomnia, anorexia, nausea, vomiting, constipation, diarrhea, abdominal cramps, metallic taste in nouth, tremors, and joint and muscle pains. All workers having abnormal signs or symptoms should be referred immediately to the plant physician for a complete examination. LEAD IN URINE Until quite recently, the techniques for the determination of lead in urine were so time-consuming and laborious that frequent examination of the urine of all exposed employees was economic ally unfeasible in many cases. In Janu ary, 1948, however. Professor Jacob Cholak of the Kettering Laboratories published a greatly simplified test for urinary lead. The method has certain de ficiencies in that it does not eliminate bismuth and certain other possible con taminants, and is only applicable to freshly voided specimens. It is ideally suited to a rapid screening technique, though, since any false results obtained will be higher than normal. This en ables one to eliminate from further con sideration all those specimens which are reported low, by a procedure which can be rapidly performed on large numbers of specimens. Utilizing this method, "spot samples" of urine should be analyzed for lead monthly on all workers in Group A, and every two months on those in Group B. "Spot samples" are advised, rather than 24-hour or other large collections, both to meet the requirement for freshly voided urine, and to avoid the danger of contamination. The variations intro duced by this method of sampling are more than compensated for by the abil ity to make frequent checks, and can be further controlled by correction for spe cific gravity. Since it has been shown that the fluctuations in urinary lead bear a ratio to the solids excreted, and the latter in turn are roughly proportional to the specific gravity, it has been rec ommended that all lead determinations be corrected to an average specific grav ity of 1.024. In essence, this merely allows for any additional water excreted through diuresis, which appears to have little or no effect on the actual lead out put. It is accomplished by determining tlie specific gravity on each specimen analyzed, and multiplying the lead value obtained by the factor 24/G, where "G" represents the last two figures of the specific gravity of the specimen. Where a corrected value of 0.1 mg. per liter or greater is obtained by this screening technique, the test should be i DU P050314422 MEDICAL CONTROL 67 repeated by one of the standard labora tory methods. This could be done on a spot sample again, or on a larger sample collected off the job. Twenty-four hour specimens collected in part during work ing hours are not advised, because of the danger of contamination. When the recheck examination confirms the find ing of 0.1 mg. or higher, the worker should be kept under observation, and examined again within two weeks. HEMATOLOGY Blood smears should be taken on all workers and studied for abnormalities, such as stippling, polychromatophilia and changes in morphology. This pro cedure should be carried out monthly on workers in Group A, and every two months on those in Group B, at the time of the periodic screening and urine ex aminations. When significant abnormal ities are found in the blood smear, it should be repeated in one week. A red blood cell count, white blood cell count and hemoglobin determination should be done every three months on each worker in Group A, and every six months on each worker in Group B. RECORDING OF RESULTS A standard form should be used for each worker giving his occupation, place of work and group classification. In per sons showing unusual susceptibility, an individual classification of the worker may be desirable. This may differ from that of his group. On this form, the re sults of each screening examination should be checked off, and all laboratory findings should be entered. This form should be made a part of the confiden tial medical records of the plant. PRE-PLACEMENT AND ANNUAL PHYSICAL EXAMINATIONS Upon institution of this plan of med ical control, a complete history and physical examination should be given each worker, and this should be done for each additional worker subsequently hired, at the time of his employment. This examination should include, in ad dition to the usual pre-placement med ical examination, a complete history of previous employments, with special em phasis on exposure to lead and an inves tigation for neurological abnormalities, blood dyscrasias, and cardiovascular and kidney diseases. Workers in these categories may be more readily injured by lead exposure. A repetition of the complete physical examination, with an interval history, should be given each worker annually thereafter. INTERIM PHYSICAL EXAMINATIONS The frequency and extent of interim physical examinations of workers by the plant physician will be determined by his review and analysis of the "screen ing" records of the individual workers, in accordance with the schedules pre viously discussed. Workers whose records indicate ab normalities should be given careful and complete physical examinations by the plant physician. When necessary, labo ratory tests should be repeated, or other laboratory data obtained as indicated. Quantitative determinations of lead in the blood may be extremely helpful in differential diagnosis. LABORATORY STANDARDS The presence of significant, hemato logical abnormalities such as stippling, changes in the color or morphology of the red blood cells, or a drop in the hemoglobin, particularly when persis tent, should be considered as a warning of incipient intoxication. The values of 0.1 mg. of lead per liter of urine, and J DUP050314423 68 SILSON 0.07 mg. of lead per hundred cc. of whole blood are generally considered the upper limits of "normal" for lead workers. Variations from the "normal" are common and can be interpreted only in conjunction with all of the clinical findings on physical examination. The laboratory provides valuable aids to di agnosis. It is not, however, a substitute for good clinical medicine. the basis of subsequent examination. Of course, where an instance of lead poisoning is due to deficient controls, it may be possible for the worker to con tinue at his job as soon as effective con trols are instituted. In cases showing unusual susceptibility to lead, it may be necessary for the worker to avoid com pletely all further exposure to this in dustrial hazard. INTERPRETATION OF FINDINGS PLANT CONTROL In evaluating the findings in a given case, considerable weight should be given to trends, such as a progressive increase in pallor, tremor, weight loss, constipation, headache, hematological abnormalities including stipple cell count, or urinary lead excretion. A lead line indicates storage, not intoxication. The development of intercurrent disease, whether or not it is the result of lead exposure, should be given special con sideration by the physician -- particu larly those conditions which tend to make the worker more susceptible to the injurious effects of further exposure. The final interpretation of the case and the decision as to what to do for a given worker will depend upon a careful evaluation of the entire medical picture, which includes both clinical and labo ratory data. RECLASSIFICATION OF WORKERS Workers in Group B who show labo ratory evidences of increased lead ab sorption without lead intoxication should be reclassified as Group A, and followed even more closely if necessary. Any worker showing symptoms or signs of lead intoxication should be immedi ately transferred to a lead-free job, or one with minimal exposure. When, if ever, such a worker may be permitted to resume his regular work should be determined by the plant physician on In addition to serving as a check on the individual worker, this screening program affords an excellent cheek on the engineering and sanitary control of the plant as a whole. The plant physi cian, carefully reviewing his medical findings by occupation and department, is frequently in a better position than anyone else in the organization to spot a breakdown in controls or an unusually hazardous type or place of work, and to recommend additional controls be fore serious illness results. Where a definite rise in lead absorption or lead intoxication occurs in a group, investi gation of the working conditions of that group should be instituted at once. This should include, air studies for lead. Wherever possible, atmospheric lead concentrations should be kept below the safe accepted standard of 1.5 mg. per ten cubic meters of air. EXPERIENCE WITH THIS PLAN IN NEW YORK STATE It is still too early to evaluate how successfully this plan is functioning in New York State. The program was only drawn up a little over a year ago, and at that time, the problem of urinary lead determinations on a large scale was still a deterrent to its practical applica tion in some plants. The incorporation of the Cholak technique into the plan has materially improved its feasibility 1 i DUP050314424 MEDICAL CONTROL since. By and large, it has been well mum of coveralls and a cap, and where received in the plants where it has been contamination is very heavy, under proposed, particularly in the larger ones clothes and socks as well. These clothes where a medical office is already in exist should replace the workers' street clothes ence. Some of the many smaller plants and not be worn over them. Provision have difficulty in getting a medical set should be made for laundering them at i \k up organized, and in arranging for the least weekly, and more often, up to laboratory work. We hope in the next daily, if necessary. In order to achieve year or two to review the findings in the these objectives, the plant management plants which have adopted it, to see may find it advantageous to supply file whether a program such as this can be necessary garments to the workers and of material assistance in improving con to launder them as often as the indi trol and cutting down the incidence of vidual situation warrants. lead poisoning. In addition, all lead workers whose shoes become heavily impregnated with PLANT HYGIENE AND SANITATION lead materials should be provided with Another phase of the problem of medical and required to wear suitable protective control of lead workers involves the footwear while on the job, which will sanitation and hygiene facilities of the not be worn home. Those engaged in the i plant. Workers exposed to lead fumes, handling of lead materials in a wet state dusts and solutions tend to accumulate should whenever possible, wear protec the material on their persons, their hair tive gloves and aprons. and their work clothes. When special precautions are not taken, they will LOCKER ROOMS carry this material home with them. This subjects the worker to additional ex Double locker rooms, with an inter posure during his non-working hours. vening lavatory, should be provided for both male and female lead workers. The i Furthermore, the possibility of ingestion first locker room, designated as the of lead, though of secondary importance, "clean" room, is where the worker dis exists when adequate drinking and lunch robes on arrival. From it, he passes room facilities are not supplied. It is, therefore, essential to make special pro through the lavatory to the "dirty" vision regarding work clothes, locker room, where his work clothes are kept. rooms and eating and drinking facili At quitting time, he can then remove his ties, to prevent contamination of street contaminated clothes in the "dirty" room, shower or wash thoroughly, and clothes, and to minimize exposure dur ing lunch hours. Along these lines, the dress in the "clean" room without dan Division has operated on a number of ger of contaminating his street clothes. Access to the "clean" room should be principles outlined below, which it rec possible without passing through con ommends to those industries where they taminated areas of the plant; and simi are applicable. larly, it should be possible for em WORK CLOTHES ployees, in their work clothes, to pro ceed to and from their jobs without con All lead workers should have available taminating offices and other clean areas at the plant special clothes into which of the plant. they can change before starting work. Both locker rooms should he designed These clothes should consist as a mini to afford maximum ease of cleaning. DUP050314425 70 SILSON The floors should be of waterproof ma terial, with sanitary bases, sloped and drained so that they can be hosed or scrubbed down readily. Lockers should have tightly closing doors with louvres or other ventilation. They should have inclined tops, and the bottoms should be continuous with the sanitary base of the flooring, to prevent dust from settling on them or collecting underneath. Sepa rate toilets should, if possible, he avail able to the "clean" and "dirty" locker rooms. All plumbing facilities, benches and other equipment should be so de signed that they can be readily cleaned. WASHING FACILITIES As was previously mentioned, the New York State Labor Law, through the Code Bulletins promulgated under it, specifically requires special washing fa cilities where lead or other toxic ma terials are handled. A minimum of one wash basin or its equivalent, equipped with running hot and cold water, must be provided for every ten employees. In addition, soap and individual towels, which may be of paper, are mandatory, and it is advisable to supply nail brushes and special cleansing agents where necessary. All lead workers heavily contaminated in the course of their work should shower every day before leaving the plant. All others should wash thorough ly all exposed parts of the body after removing their work clothes and before dressing. They should be advised to bathe and wash their hair at least twice a week. Washing or showering should be done under factory supervision, and at least ten minutes should be allowed at the end of each shift for this pur pose. A minimum of one hot shower should be provided in every lavatory for emergencies, with additional ones on the basis of one for every five workers requiring daily showers. LUNCH ROOMS As stated earlier, the New York State Labor Law provides that in all indus tries handling lead, the workers are not permitted to bring into or eat in the workroom any food, that a notice to this effect must be posted, and that some place for them to eat their food must be provided. While theoretically, space set aside in a locker room fulfills these re quirements, it is not a satisfactory solu tion, because, with the set-up described above, the workers would either have to eat in the "dirty" room, where their food could become contaminated, or else in the "clean" room, which would re quire them to shower and change their clothes to avoid contaminating it. Since it is inexpedient for them to do this at lunch time, lunch room facilities should be provided for all the workers, wher ever possible. The type of facility would vary with the size of the individual plant and the habits of its workers, ranging from a room in which to eat lunches brought in, to a full cafeteria service. The room should be constructed with waterproof drained floors, sanitary bases, and readily cleaned tables and benches, so that it can be hosed down after each meal period. Workers should not be permitted to return to the "clean" locker rooms during lunch hours: to this end, a cubbyhole for each worker should be provided in or near the lunch room in which he can leave his lunch on ar rival in the morning. Unless the lunch room is located sufficiently close to the locker rooms so that the latter's facilities can be utilized, a separate wash room should be provided adjacent to it. It should not be located where contamina tion from the workrooms is likely. In i n DUP050314426 MEDICAL CONTROL 71 larger plants, the lunch room is some unit should be set up, from which the times placed adjacent to a yard or other respirators would be issued daily or as enclosure in which the workers can eat required, and collected, cleaned, steri their lunch or relax out-of-doors, if they lized, tested, and if necessary repaired, so desire. It is recommended that, as a ready for reissue. When a worker re minimum, a dispensing machine for quires one constantly, he should be pro beverages, preferably milk, be provided. vided with two, which are exchanged 1 Efforts should be made to discourage daily at a fixed time under proper con the workers from eating in neighbor trol. A convenient arrangement is to hood lunchrooms in contaminated put the respirators into individual paper clothing. bags, identified for each worker, after An abundant supply of drinking maintenance has been performed. The water should be maintained by the use maintenance and issue of respirators of angle jet fountains. Where these should be under the direct supervision cannot be provided, water should be of the medical department or the safety supplied outside of any workroom where engineer. When respirators are used lead processing is done, and individual intermittently by the workers, they will paper cups should be furnished. as a rule leave them suspended about RESPIRATORS their necks when not in use. Frequently, this results in contamination of the in While the Division does not in general side of the respirator from contact with approve the use of respirators as a means lead-impregnated work clothes. To re of control, there are certain special cir duce this to a minimum, it is recom cumstances where they must be used, mended that the worker be issued a either because engineering controls are plastic bib against which the respirator impossible for the particular operation, can rest. The smooth surface will shed or because the operation is so infre dust more readily than the work clothes, quent as to make elaborate ventilation and can be kept clean more easily. unfeasible. In addition, in certain in stances, respirators may be required in APPLICATION IN NEW YORK STATE addition to engineering controls. Air In the application of these principles line respirators are indicated whenever to various plants and industries in the exposure is heavy or work is done New York State, considerable flexibility in a confined space, as for example, is allowed, and each instance is treated when cutting red-leaded steel in a ship's as an individual problem. The extent to hold; for lower exposures, a cartridge or which each of these principles can be canister type of respirator approved for applied in a particular plant is discussed the particular nature of the lead ex with the management, and a program posure, such as dust, fume or mist, may agreed upon which is both feasible and be adequate. Maintenance and cleaning adequate. Moreover, since many of men especially, whose work carries them them are merely recommendations, and all over a plant and into areas where not enforceable by law, we try to demon the local or general ventilation may not strate how their adoption will be of be effective, should be protected in this benefit to die industry. The following way. examples illustrate our approach: When respirators are used, their main An ideal opportunity presented itself tenance should not be left to the indivi when we were approached by a com dual worker. A centralized respirator pany manufacturing pottery decalco- DUP050314427 72 SILSON manias to help them plan for the con- extremely accurate, it is necessary to trol of the lead hazard in a new plant air condition the press room to avoid they were in process of building. Al- changes in paper size due to varying most all the pigments used in printing temperature and humidity. The com- tfaese decals contain lead borosilicate as pany had planned to recirculate all of a flux and some, in addition, contain the air for this reason, but the Division other lead salts as a basic color. The felt this to be inadvisable. Studies were majority of them are dusted onto the therefore made on the presses, dusters, sheets after printing the pattern in var- and brushes in the old plant, and local nish, and the excess powder is then ventilation designed which would reduce brushed off after the varnish has dried, the air contamination with a minimum Although lead borosilicate is considered volume of exhausted air. The duct sys- less toxic than some of the more soluble terns and collectors were then integrated salts, the dusty character of these opera- into the plans for the new building, tions still creates a real hazard requir- It was agreed to recirculate none of the ing careful controL local exhaust air and a maximum of The company roadily accepted our 20% of the general room air, and pro suggestion to set up a program of medi- visions to condition an adequate amount cal control in accordance with the pre- of make-up air were therefore included, viously discussed outline, and a medical Another special problem came to the oESce with adequate space and facilities attention of the Division through a case for putting such a program into effect of lead poisoning in a newspaper stereo- was incorporated into the building typer. The plant in which he worked plans. In addition, numerous alterations was a clean and up-to-date one, which were made in the layout of the locker would normally not have been sus- rooms to conform to the above sugges- pected. Air tests made in the breathing tions, and a lunch room, which had riot zones of the workers revealed values been projected, was included in the re- two to three times the maximum allow- vised plans. After much discussion, it able concentration for lead in the was decided that the lead contamination breathing zones of the workers at all was not sufficiently great to warrant operations. Further studies then showed compulsory showers, but one shower the lead in the general room air to be for emergencies was included in each uniformly high, and determinations lavatory. Double locker rooms, in place made at the possible points of origin of a larger single one originally planned, indicated that this was due, not to fumes . were designed, with entrances so ar- from the melting pots or pouring opera- ranged as to avoid contamination of' tions, as was first suspeoted, but to fine : clean areas of the building. A larger particles dispersed in the air by the cut- number of washing facilities than had off saw on the caster. A special means been originally thought necessary were for locally exhausting this saw is being also included. ' devised, and a program of medical In addition to the medical and sani- examinations for the workers has been 1 tary aspects, the Engineering Unit of recommended to the company, the Division was able to supply consid- Still another case of lead poisoning- erable assistance in planning the ven- was reported in a worker in another tilation controls in the new plant Since plant who was spray painting the backs each color is printed with a separate of mirrors with a special lead-containing press run, and superposition has to be paint Here the exposure was due to DUP050314428 MEDICAL CONTROL 73 faulty design of the spray booth. Re design of the booth, and the additional use of cartridge respirators proved to be the solution; and arrangements were made with the plant physician for a periodic medical check-up on all the ex posed workers. CONCLUSIONS In conclusion, then, the New York State Division of Industrial Hygiene and Safety Standards has prepared an integrated program for the medical con trol of lead workers. A system of peri odic screening examinations under medi cal supervision is recommended, which includes an evaluation of symptoms, a limited physical examination, and blood and urine tests; and in addition, a com plete examination by the plant physician at least annually. This serves as a check both on the individual worker, and, by analysis of the data by groups and de partments, on the occupation and work room. Further recommendations have been made for special considerations in planning locker and lunch rooms, and for a well-rounded program of individ ual and plant hygiene. A means for safely using respirators when necessary has been proposed. By and large, this program, when combined with proper engineering controls to remove most of the lead at its point of origin, and peri odic air tests to check the efficiency of operation, should enable a plant to re duce the incidence of lead poisoning to that of a rare phenomenon, and to im prove the health and morale of all its workers. Ch a ir ma n Bo w d it c h : Our next and final speaker of the afternoon has been selected to lead the discussion of Dr. Silson's paper because of his long and important connection with the Connec ticut State Department of Public Health, where he was industrial hygiene chem ist from 1928 to 1937. During that period, he was chairman of the Engineering Committee of the National Silicosis Conference, and more recently has been chairman of the Com mittee on Determination of Atmospheric Contaminants of the American Public Health Association. He is now director of the Division of Industrial Hygiene and Engineering Research of the Zurich General Accident & Liability Insurance Company. Mr. .Warren A. Cook. DISCUSSION Mr . Wa r r e n A. Co o k [Director, Di vision of Industrial Hygiene and En gineering Research, Zurich General Accident and Liability Insurance Co., Ltd., Chicago, Illinois]: With the in corporation of all the elements outlined in the medical control program pre sented by Dr. Silson, I think we will agree that the possibility of development of lead poisoning would indeed be low. There are a number of points, however, which I feel might be introduced to increase the practicality of such a pro gram. Frequencies of periodic examinations of workers, their blood and their urine, were presented, based upon the occu pation or operation involving the lead exposure. This should serve as a valu able guide. However, the results of one or two initial series of such tests should influence future frequencies of them. Assuming negative results from the physical examinations and blood tests, DUP050314429 74 DISCUSSION the magnitude of the exposure as indi use of air line respirators, or other con cated by concentration of lead in urine trol measures. serves as a better criterion of preferred In the matter of work clothes, the frequency of all these examinations than wearing of gloves was mentioned in can any fixed schedule. handling wet lead compounds. If Dr. For example, spray painters were Silson had in mind skin absorption of listed in classification A. Spray painters lead, I assume that he was referring to may be exposed to a small amount of organic lead compounds such as lead lead, where the lead' may be present tetraethyl inasmuch as we need not be only in the proportion of Vs percent as too concerned about skin absorption of a drier. Or we may have an olive drab inorganic lead compounds whether wet paint with 7 percent lead chromate, or or dry. the paint he red lead itself. Certainly, In discussing the matter of respir we would not feel that a worker who is ators, cartridge respirators were men spray painting in front of a well-ex tioned. Though these are in order for hausted spray booth, with a paint which solvent vapor protection, filter type res might contain % percent of lead naph- pirators are more effective for lead dusts thenate as a drier should be examined and fumes. at the frequency required under classi In regard to maintenance of respir fication A. ators, one of the best procedures is that On the other hand, if spray painters published by the industrial hygienist of happened to be removing red lead paint the Allis Chalmers plant at West Allis, with a power-driven scratch brush in a Wise., in the March, 1948 issue of the confined area prior to painting, an early American Industrial Hygiene Associa examination might show sufficiently high tion Quarterly. This covers both the exposure that a second series of tests cleaning and the sterilizing and handling would be indicated within a week. of respirators from a maintenance point Schedules should certainly be set up as of view. outlined by Dr. Silson, but these should It should be emphasized that the great he shifted one way or the other accord importance of lead-in-urine analyses in ing to the exposures of the individual the lead hygiene program is that of a group. control measure. The real value of these As a recent example, we wanted to be analyses is to determine whether the certain that there was no excessive lead worker is exposed to enough lead to exposure in cutting up some of the cause lead poisoning, rather than to de LSTs and DE's that were built during termine whether or not he may have it the war. Our general information was after he has been heavily exposed. that the shipyards had used zinc chro As to whether the worker should be mate primers and only the small percent told what his lead-in-urine result is, I of lead for the driers in the gray finish feel, personally, that the local situation coats. should govern the decision. The attitude To our great surprise, on checking of the individual group of workers and the paint chips from a number of DE's, their relation toward management, the we found from 8 to 20 percent lead. number of them, what you expect to, We accordingly started with a high fre find and what you expect to do with the quency of lead-in-urine analyses to de lead-in-urine results are all factors. termine whether the exposure to lead Our experience in certain other plants could be kept to satisfactory limits by has been that the lead-in-urines can be | DUP050314430 MEDICAL CONTROL 75 used to enlist the greater cooperation of program, we also insist that medical the individual worker. control is an essential. For example, in one spray painting Ch a ir ma n Bo w d it c h : Mr. Cook department where lead chromate was made reference to paints used by the being used on large machinery, lead-in Navy. I wonder if Dr. Brown would urines were run. At the end of one care to comment on what Mr. Cook said month, we collected another set of urine on this subject. samples. The workers were very much Dr . Er n e s t W. Br o w n [Council on interested in the results of the first Industrial Health, American Medical samples. Association, Chicago, 111.]: The later We indicated that one test didn't methods of control? mean too much, but told the men that Ch a ir ma n Bo w d it c h : No. He spoke the results were low or average for such of the nature of the paints that were work according to the results. In one used on ships. Would you perhaps re case where the result was high, we told peat what you said about this, Mr. them that this one test did not mean that Cook? his health was affected but it did mean Dr, Brown, of course, was in charge that he should reduce his exposure or of industrial hygiene research in the he would be getting loo much lead and Navy during the war. might develop symptoms if he continued Mr . Co o k : I am very glad Dr. Brown to breathe in too much lead over a period is here to give us the answers on the of time. We inquired whether he was lead paint on these ships. On the LST wearing his respirator all the time, or we found only 0.45 percent lead as the whether he carried it on the side of his naphthenate in the drier. On the super face. Did he make sure not to get in line structure and various other parts of the with some other operator's spray gun LST, there were similar low percent and was he careful to avoid working ages. between the parts being sprayed and On one DE, we found 20.6 percent the exhaust ventilation. lead. A second DE ran about 21 percent We took another group of samples at and three others gave 8, 16 and 15 per the end of the next month, and every cent lead. one of them was well down. We length Since the only lead in the paint used ened the frequency to a quarterly period, on Navy ships in the yards with which but did not further extend the period we had contact during the war was the because we felt that at any time the half a percent used in the drier, your workers could get careless and over information on the probable source of expose themselves. Thus we let both litis lead paint would be of very great the type of work being done and the interest. results that we had obtained fix the Dr . Br o w n : Yo u probably know, Mr. frequency of the lead-in-urine determi Cook, that the Navy abandoned the use nations. of lead paints officially in December, In discussing a medical program in 1941 and went to another pigment from industry, I should not fail to express that time, namely zinc chromate. an opinion which is very firmly fixed The DE type of boats were built with me, and. I am sure with most indus during the war period; therefore, should trial hygiene people. Whereas we may have been painted officially with another place much emphasis on the laboratory type of paint and not with lead paint. and technical phases of a lead hygiene I think, however, there was some DUP050314431 76 DISCUSSION bootlegging in regard to red lead paint, despite the official instructions from headquarters. I know that a certain number of ships did get red lead on them. Dr . Le o n ar d J. Go l d w a t e r [Pro fessor of Industrial Health, School of Public Health, Columbia University, New York, N. Y.]: In our experience, we found the only time we ran into lead paints was on ships of foreign countries which were here for repair, particularly British ships. When they came in and needed some burning or cutting or weld ing done, we had to watch out for lead poisoning; in fact, we saw some cases of lead absorption, but not on the ships of our own Navy. It may be that some of those that Mr. Cook has run into were at some time in foreign yards for over haul or repair and got some British or French or some other kind of lead paint on them, but the Navy, just as Captain Brown said, had practically no lead paint. Dr . Br o w n : I would like to add another point. While the Navy discon tinued the use of red lead paint in De cember, 1941, it authorized the con sumption or using up of all stocks on hand, which probably were extensive, involving quite a considerable carry over. [Laughter] Ch a ir ma n Bo w d it c h : As one of our outstanding veteran state industrial hy giene administrators, I wonder if Dr. Gray would like to add anything to the discussion of Dr. Silson's paper. Dr . Al b e r t S. Gr a y [Director, Bu reau of Industrial Hygiene, Connecticut Department of Health, Hartford,Conn.]: There is nothing I care to add, Mr. Bowditch, except to emphasize -that medical control is a very big factor in this whole story. We utilize it in Connecticut, and it has been shown very definitely that it checks up the engineering and it checks up the carelessness of the individuals who are working in these lead industries. It is very necessary, I think. Ch a ir ma n Bo w d it c h : Are there any further comments? Mr . G. C. Wa l t e r s [National Lead Co., Chicago, 111.]: I would like to ask Dr. Silson about his comment on the spot sampling for urine, because of con tamination of a more elaborate sample. Do you mean the sampling within the plant? Dr . Jo h n E. Sil s o n : We feel that, for frequent checks, spot samples are quite adequate and the most simple to collect. If a larger specimen is wanted for re check, then we like to see off-the-job samples collected; 24 hours, over Sun day, when the worker is not working; or maybe two or three nights at home, without collecting the daytime samples while he is in the plant. But to have them collect a 24-hour sample during die work week, we feel, brings up too great a danger of contamination. The worker has to carry a botde with him, and he almost invariably contaminates it. Mr . Wa l t e r s : I wondered how Dr. Belknap gathered the 24-hour sample. Have you any absolute way of knowing it is the urine pf the man in question? Do you gain better results by having a 24-hour sample than you would by a spot sample? Dr . Be l k n a p : Well, we have no guar antee, of course, that it is not a sample of the entire family [laughter] while the man has gone fishing over the weekend. But, just like anything else, in evaluat ing a man's symptoms from frequent re-checks if you know the man per sonally you can tell pretty well whether he has been cheating on this urine proposition. It just seems to me that, when one is dealing with millionths of a gram, really of lead, even in a liter sample, of 2,000 cc. sample, you would have less error if you studied a larger sample MEDICAL CONTROL 77 than a spot sample. The problem may be a medico-legal one. I simply would like to say, in regard to this urine lead study, that I have no. quarrel with col lection of urines. I think we are going to learn a lot more in the procedures as suggested by Dr. Silson, using the Cholak method, and Dr. FairhalPs short method can probably be used also. But we have to have something to tell a man who has the idea that he has lead poi soning, or his doctor has told him that he may have lead poisoning. That is the problem. You can eventually, by your engineering technique and air con trol, have your air concentration and your resultant urine lead down to within safe limits, but you still have the psy chology of the patient who knows that he is working with lead and fears it in any amount. The hemo-stippled cells and lead line of the gums are quicker to determine and more diagnostic than urine leads done regarding actual lead intoxication. Unless you have something specific that you can say whether or not he has anemia, or whether he has a lead line, stippled cells or any other evidence of possible lead absorption or lead intoxi cation, then you are at the mercy, really, of the man's family doctor. In many cases, if the family doctor is well in formed, you can rely on his cooperation. However, there are instances where you cannot afford to let the family physician merely speculate regarding lead absorp tion versus lead intoxication. Ch a ir ma n Bo w d it c h : We have run well beyond our closing time and I should therefore postpone further dis cussion of stippled cells versus urine until after lunch tomorrow. We stand adjourned. DINNER SESSION November 16, 1948 Pr e s id e n t Wo r ms er : Our guest of honor and speaker of the evening is a graduate of Cornell University, Class of 1918, where his athletic prowess earned him recognition as an All-American tackle. He has continued his interest in sports, particularly football, as an ad viser to the Chicago Bears, and is an amateur aviator. His entire professional career has been spent with the Inland Steel Company, and LIFE recently re produced his photograph as an excellent illustration of a self-made man who has worked his way up to the top from hum ble beginnings, and of what can be done by Americans under our system of free enterprise. With his vast experience in handling men, I am sure you arc in for a treat in hearing his views on industrial health. I take great pleasure in present ing to you Mr. Fred M. Gillies, Works Manager of Inland Steel Company's In diana Harbor Works. THE PRODUCTION MANAGER LOOKS AT INDUSTRIAL HEALTH By FRED M. GILLIES IForIts Manager, Indiana Harbor Works, Inland Steel Co., East Chicago, Ind. The industrial progress of America is situation and unfair standard of human controlled completely by two men. One values could not possibly give America is the production manager--the other the production record it enjoys today. the worker. And, as for social problems increasing, Modern industry requires both ma that may be true to some degree, in so chines and men. Machines must be de far as the population is increasing, but signed by men and they can not produce is more reasonably explained by the fact without operators. Machines must be that we are today more aware of social serviced by men to be kept in efficient problems, just as we have become more operating condition. So no matter how aware of the early signs and symptoms ingeniously we design machines, we still of cancer and other diseases. must devote most of our attention to the During 1948 the index of production men who operate and service them. We per man hour is approximately 30 per i cannot: design men like we do machines, cent greater than it was ten years ago, we have to take them as God gives them and it is about 60 percent greater than to us, but we can care for these men, and it was 20 years ago. It is not unusual see to it that they operate efficiently. today for production to exceed 100 per Here is where the production manager cent of rated capacity. In buying power comes into the picture. a United States worker makes more than Somehow, there has been developed a twice as much as a British worker, un feeling that productivity in America has der a Socialistic government; and ten expanded at the expense of social jus times as much as a Russian worker, tice. Also, the idea has been advanced under a Communistic system. Somehow, that human problems are increasing due as a production manager, I cannot quite to industrial pressures. We believe these see how we compare unfavorably with assumptions are false. An unjust social the rest of the world in matters of social 78 DUP050314434 PRODUCTION MANAGER LOOKS AT INDUSTRIAL HEALTH 79 justice, human values, and personal hap piness. The degree of production depends en tirely upon men. The production that men may deliver is directly related, among other things, to the state of men tal and physical health. For that reason, industry is interested in maintaining good health in its workers. However, progressive industrial leaders feel that production should not be the sole reason for an interest in the health of workers. The merit of the humanistic attitude is clear to all of us today. It is quite apparent that industrial medical service can not and should not do the whole job of looking after the health of its people, and it would be impossible to do so even if industry wanted to, because of such factors as weather, epidemics, domestic problems, etc., all of which play their part. How ever, industrial medical service can go a long way toward the ideal by providing an ethical medical program suited to the particular needs of the industry. In the interests of production, indus try should have the answers to several questions: Is the health of the worker suitable to the job? Does the worker maintain that degree of health as he continues to work on the job? Is the environment in which he works safe and healthful and reasonably free from annoyances? Does the worker understand how to keep himself in a healthy state? The answers to these questions can be provided only by the doctor and hy gienist. When greater production is called for in our normal competitive scheme of things the production man ager should get better results if he has made it a practice to interest himself in the health problems of the worker. Naturally, at this point there might be some question that this would be more effective for morale than an increase in pay. It has been said that if the indus trialist could forget about profits, the workman forget about pay, and the poli tician forget about votes, our troubles would be over. The production man naturally believes in private enterprise, and it follows that he is interested in how much and how far medical and hygiene services are to be extended to employees. Because a thing works well, there is often a tendency to over-do it In the case of industrial med icine and hygiene, the production man ager feels that the same principles that apply to private enterprise should apply to medical services within industry. Briefly such services should probably include: Medical and surgical services for those who are injured or made ill by their jobs. Emergency services, within ethical limits, for non-industrial illnesses or injuries. Pre-employment and periodic physical examinations. Industrial hygiene surveys and serv ices within the industry. General health education and advice. All other things, including the treatment of non-industrial illnesses and disease, preventive medicine and public health, should properly lie outside of manage ment. Although the industrial medical de partment should cooperate with public health agencies and private practitioners and assist wherever possible in commun ity health programs, the prerogatives of such agencies should not be infringed upon by the industrial doctor or hy gienist The reverse situation should hold equally well. DU P050314435 80 GILLIES In administering such a program, it is probably well to remember that the in dustrial doctor and hygienist are trusted representatives of management, whose chief interests are in maintaining the health of all employees, including those in management. It has occurred to me that the indus trial doctor and hfgienist perform a very valuable and important function in the labor and industrial relations pic ture, directly or indirectly. The intimate problems of personal health and happi ness can not be adequately discussed and solved anywhere as well as they can in the privacy of the doctor's office. This is especially true if management respects the confidential relationship, which must exist between the doctor and the em ployee. In our busy world of today, which is becoming very crowded and where life has become more complex, it is neces sary for the industrialist in charge of production to step back from time to time and take a look at himself in sharp and candid focus. He should examine the philosophy of his daily life and the things he does to see if he is contrib uting something to relieve die fears and bitterness which beset and plague us. The sincere and friendly interest that modem industry is taking in the health of its workers will help in a large way to dispel some of the conflicts that have existed in the past. I DUP050314436 TUESDAY MORNING SESSION NOVEMBER 16, 1948 Ch a ir ma n Bo w d it c h : Our first paper this morning will be by a man who was Acting Chief of Research of the U. S. Food and Drug Administration during the war and is now Scientific Director of the Research Branch of the National Cancer Institute. On the basis of his very extensive animal experimentation with BAL, Dr. Harry Eagle will speak on "The Effect of BAL on Experimental Lead Poisoning." THE EFFECT OF BAL ON EXPERIMENTAL LEAD POISONING By HARRY EAGLE, M.D. Scientific Director, Research Branch, National Cancer Institute, Bethesda, Mi. BAL was developed in the early days of the war by a group of inspired Brit ish investigators under the leadership of Dr. Peters, Dr. Stockton and Dr. Thomp son, primarily for the treatment of po tential injuries caused by the arsenical war gases. I will not detail the events that led to the development of this compound, other than to say that it began with the almost chance observation that when certain toxic arsenicals were allowed to react with tissues, they combined with twice as much tissue sulfhydryl groups as they should have on the basis of the then ac cepted ideas as to the mechanism of the reaction between arsenical and tissue SH groups. In the top right-hand corner of Fig. Is is the chemical structure for BAL 2, 3dimercaptopropanol. This was only one of many com pounds which were synthesized and found able to compete with the tissues for the possession of arsenic. Even after an arsenical war gas had reacted with and combined with tissues Land pre- *The figures and-tables included in this manu script have been reproduced from a number of previous publications listed on page 91. Fig. 1--The top right-hand corner is the chemical struc ture for BAL 2, 3-dimercaptopropanol and in the top left-hand corner is the tissue-arsenic compound formed after arsenical war gas had reacted and com bined with tissues. DUP050314437 82 EAGLE sumably with suifhydryl groups in those tissues] to form a tissue-arsenic com pound which is illustrated in the top left-hand of Fig. 1, the BAL could com pete effectively with the tissue suifhydryl groups for the possession of the arsenic to form a Bal-dithioarsenite. Monothiols, such as cysteine and glutathione which were far less effective than these dithiols in competing with tissue suifhydryl groups for the possession of the arsenic. During the war, also, Dr. Barron and a number of others in this country showed that arsenicals generally were able to inactivate a large number of en zyme proteins containing suifhydryl groups, and that BAL could reverse the inhibitory effect of arsenicals [and also of mercury compounds]. It seemed probable that the toxic effects of arsenic on tissue was due to the fact that they combined with and thus inactivated cer tain sulfhydryl-containing enzyme pro teins in tissues, and that the reversal of that combination by BAL was the basis of its therapeutic action. When it was originally developed, BAL was first thought to be of value merely as a local antidote to the skin and eye injuries caused by Lewisite, Adamsite, and the other toxic arsenical war gases which were used, to limited degree, in the first World War, and on which there has been some study in the intervening period. Fortunately, the use of the arsenical war gases did not materialize in this war, and the use of BAL for the treat ment of certain types of metal poison ing, has thus been a by-product of a war scare. It soon developed that the favorable therapeutic effect of BAL on gas poison ing would not be limited to its local effect on skin areas or eye areas wbich had been damaged by contact with these gases. Even when BAL was given systemieally, it had favorable effect on animals which had already gone on to develop systemic evidence of arsenic poisoning. For example, we injected some rabbits with mapharsen at 20 mg. per kilogram which in man corresponds to about 1200 mg. and which is reg ularly fatal. The rabbits immediately developed signs of distress, vasodilata tion, dyspnea, and died within a short time. If, five minutes after the initial injection of mapharsen, and when the animal was already in acute distress, it was given an injection of BAL, there was a spectacular recovery, and within half an hour. This makes for a striking classroom demonstration. Under the microscope, if one takes a suspension of, for example, trypano somes, which are extremely sensitive to most of the trivalent arsenicals, and adds one of these arsenicals in sufficient con centration, the organisms are immobil ized almost instantaneously. Within a few minutes any one familiar with their microscope appearance would say, "These are dead organisms." They have become globular and vacuolated, and have swollen to about twice their nor mal size. if, at that point, one adds a little BAL in solution on to the slide, the trepanosomes, like Lazarus, rise from the dead and resume their normal, elongated form, and become actively motile. This also makes for a pretty laboratory dem onstration. Table I illustrates this resuscitating experiment. If one adds some BAL to a suspension of "killed" trypanosomes, less than one minute after the rddition of the arsenical, more than 95 per cent of the organisms are resuscitated by as little as l'/o molar equivalents of BAL. The longer one waits from the time of the addition of arsenic to the time of revival by the addition of BAL, the less successful the results. Thus, after 30 minutes, only around 10 per cent of the h DUP050314438 BAL 83 organisms are revived, no matter how much BAL was added. By that time a fair proportion of the organisms had al ready lysed, and tlieir resuscitation would involve reassembling the organism. The right-hand portion of the table shows that, in this respect, cysteine and, indeed, any monothioj, is far less effec tive than BAL. To revive 95 per cent of the organism with cysteine, for exam ple, required 1,250 molar equivalents, instead of 1%. That is a measure of the far greater affinity of the dithiol for the arsenic. The effect of BAL in counteracting systemic arsenic poisoning is due to the fact that it can compete successfully with a tissue dithiol group for the possession of arsenic. This is shown in Table II. Trypanosomes combine with arsenic, and are able to concentrate some of these toxic arsenicals to an extraordi nary degree, so that the concentration of arsenic in the organisms is 100 and even 200 times greater than in the surround ing fluid. The figure in the last column of the table is the ratio of the concen tration of arsenic in the trypanosomes to its concentration in the surrounding fluid. If, to such a suspension, one adds some BAL, the drug abstracts the ar senic from the trypanosomes and strik ingly reduces the concentration of ar senic in the trypanosomes relative to that in the fluid, e.g. from 257 to 28. In another experiment with phenyl arsenoxide the hydrolyzed form of one of the war gases, the ratio of concentra tions was reduced by cysteine acting in concentration of 0.OIM from 143 to 33, but, by BAL, in one-tenth that concen tration, down to nine. I should say at this point what BAL stood for. When the material was still in the secret category some of our col leagues learned enough about it to spec ulate that BAL might stand for bismuth, arsenic and lead [Laughter]. This was, in the light of what we now know, a very shrewd guess indeed. Actually, BAL stood for British Anti-Lewisite, because it was first developed for the treatment of lewisite poisoning. Those of us working with the com pound--I am sure Dr. Corwin would subscribe to this--were always a little puzzled at the secrecy which surrounded the material. It required little more than a sub-average sense of smell and a TABLE I The Resuscitation of Arsenic-Poisoned Trypanosomes by BAL and by Cysteine Trypanosomes were completely immobilized in one minute by the addition of phenyl arsenoxide to 10-5 molar concentration. Sulfydryi compounds were added at Ihe intervals and in the amounts indicated. Time organisms exposed to arsenical before addition of --Sfi compound <V 5' 15' 30' Molar equivalents of -SH compound added SAL Cysteine 12 6 3 IVe % 2500 1250 625 312 156 Proportion of motile organisms 60 minutes after addition of -SH >95 >95 >95 >95 0 >95 >95 84 0 0 >95 >95 92 00 79 77 41 0 0 73 50 40 0 0 20 20 6 0 0 12 15 4 0 0 0 0 000 DUP050314439 84 EAGLE laboratory able to do some elementary analyses to arrive at the complete struc ture of BAL. However, it remained in the top secret category, and everyone nearby was unhappily aware of the fact that somebody in the place was working with mercaptides. One difficulty with the possible syste mic use of BAL was its great lability, the fact that it not only easily oxidized but rearranged, and that it did not hold up either in water or in propylene gly col. We found, however, it could be stabilized by solution in peanut oil and benzo-benzoate, and that in glass sealed ampules such solutions could be auto claved with a minimal loss in activity. The ampules have now held up for something like five years, with no ap parent loss in activity, and no change in their iodine titration. The fact that BAL acts by abstracting arsenic from the tissues was clearly shown by its effects on the urinary ex cretion of arsenic. Fig. 2 illustrates an experiment in rabbits which had been poisoned by the injection of lewisiie, not locally applied to the skin but actually injected. As you see, when BAL was administered 24 hours after the original injection of lewisite, there was a striking effect on the rate at which the arsenic was ex creted in the urine. You will note that this effect is tempo rary. The effect of a single injection of BAL is done and over with in two to four hours. For the first two hours, there is a striking effect on the excretion of arsenic. In the succeeding two hours the effect is less, and, thereafter, the rate of excretion falls to essentially normal levels. This suggested that, if BAL was going to be used therapeutically in man, these oil solutions of BAL would have to be injected approximately every four hours, in order to have a maintained, continuing effect. Fig. 3 is an experiment with a differ ent arsenical. One sees the tremendous TABLE I! The Removal of Arsenic from Trypanosomes by BAL and by Cysteine {Trypanosoma! suspension =: 1.9--3 x 10s per ce.l Arsenical added Micrograms Compd. used per cc. -SH compound added Com- Time Final a her concern, pound arsenical tration Condition of suspension 60' after addition of --SH compound % Motile Ratio of arsenic concn. in trypanosomes arsenic concn. in supernatant Phenyl arsenoxide 0 1.67 Cysteine BAL 10'* 10'* 0.01M 0.001 M 0 43 81 154 33 9 p--Carbamido- 0 3' -- 0 phenyl 1.67 arsenoxide BAL 3' 0.002M >95 257 28 05 --0 Mapharsen 1.35 BAL 5' 0.0002M >95 118 15 All organisms immobilised at time of addition of --SH compound. DUP050314440 BAL -------------; - ---------------------------------------------------- 85 v,. effect on the urinary excretion of ar Two experiments were started, one in senic, when BAL was injected even 24 some prisoners who volunteered for the hours after the administration of die study, and the other in a group of peo " arsenical. The dotted curves in the lower ple who came to the Rapid Treatment left-hand are the rate of excretion in the Center for anti-syphilitic treatment. control, untreated rabbits. Although the lethal dose in animals, The next step was to attempt to on a single injection was something like apply these findings in man. Although 40 mg. per kilogram, we began with there had been a great deal of study on the toxicity of BAL in experimental animals, those of you who have ever tried to extrapolate toxicity data from mice, rabbits or dogs to man, are also aware of the fact that that extrapolation is fraught with danger. Usually one encounters in man toxic reactions which one does not see in animals, and often % mg. per kilogram; and I am very glad we did. As long as the dosage levels were less than 2% mg. per kilo, per injection, there was no difficulty. As soon as the dosage exceeded 2Yz mg. per kilo, there were rather frightening reactions, the severity of which was pro portional to dosage. There was lacrimation, a sense of burning in the mucous membranes, gen at dosage levels which in animals have eralized aches and pains. But more dis no demonstrable effect. turbing than any of these was a sense Fig. 2--The effect of BAL (injected intramuscularly in peanut oil benzyl ben zoate solution) on the urinary excretion of Lewisite in rabbits. Lewisite was injected intravenously in propylene glycol solution (0.69 mg. per kg.). Twentyfour hours later the rabbit was given a single intramuscular injection of 10 mg. per kg. BAL (5 per cent solution in peanut oil with 10 per cent benzyl benzoate). Urine specimens were obtained by catheterization just before the injection of BAL, and 4, 8 and 24 hours later. O O Hours After injection of LewisiTe Single intravenous injection (0.69 mg./kg - 0.0033 mmol./kg.) DUP050314441 86 EAGLE Hours After Injection of Phenylarsenoxide (0.56mg./kg.) Fig. 3--The effect of BAL (injected intravenously in saline solution) on the urinary excretion of phenylarsenoxide in rabbits. A rabbit was injecletl intravenously with 0.56 mg. per kg. phenyl arsenoxide. Twenty-four, 48 and 72 hours later the rabbit was given an intravenous injection of 10 mg. per kg. BAL in saline solution. Urine specimens were collected by catheter ization just before and 4 hours after each BAL injection. The'open circles at the bottom of the figure refer to two control rabbits receiving no BAL. The striking effect of BAL on the hourly excretion of arsenic is indicated in the cross-hatched blocks at the top of the figure. of anxiety, a sense of preeordial com pression, and in a fair number of cases, at these upper dosages, a rather striking increase in blood pressure. All of these effects were temporary, and had largely disappeared within thirty minutes. Nev ertheless, we felt that we ought to recommend dosages not to exceed 2% to 3 mg. per kilo. A considerable number of patients with arsenic poisoning were treated with BAL. Our first report included some 227 cases of various types of arsenic poisoning, most of them occur ring as complications of antisyphilitic treatment in the pre-penicillin era. Those included cases of arsenic der matitis, hemorrhagic encephalitis, blood dyscrasias, jaundice, mistaken admin istration of massive doses of arsenic, and the rather mild complication con sisting of fever and headache which is often, however, a premonitory symptom of beginning toxic encephalopathy. The results were gratifying. In cases of dermatitis although there were a few DU P050314442 BAL 87 which were refractory, and although the occasional case developed an abscess caused by a needle going through an infected area involved by the dermatitic process, the average hospitalization pe riod was reduced from the many weeks and months with which you are all familiar to an average of something like 13 to 15 days. The symptomatic relief in 48 to 72 hours was sometimes quite dramatic. In the cases of toxic encephalopathy, Fig. 4--The effect of BAT. in cases with agranulocytosis. At the point marked zero in the abscissa, BAL was given. Time in Days After Beginning BAL Therapy M DUP050314443 88 EAGLE exactly as we found with trypanosomes and rabbits, the longer one waited be tween the onset of symptoms and the administration of the BAL, the worse the results. If BAL was not given for six, twelve or twenty-four hours after the beginning of evidence of cerebral damage, its therapeutic effects were rather minimal. If, on the other hand, BAL was given within six hours or less, after the beginning of symptoms of cerebral involvement, the results were quite gratifying. Our mortality in this group was something like 15 percent as compared with 50 to 75 percent in a control group. In arsenical jaundice it did very little. There was an occasional case which re sponded dramatically, but most cases re sponded hot at all. This raises, again, the old question which you will find discussed at length in the standard hand books on syphilotherapy, as to the causa tion of so-called arsenical jaundice: whether it really is caused by the arsenic, or whether other factors may, perhaps, supervene. In the blood dyscrasias, BAL did nothing in the cases which involved aplastic anemia, but was effective in cases of agranulocytosis. Fig. 4 shows the effect of BAL in cases with agranulocytosis. At the point marked zero in the abscissa, BAL was given. The regular increase in the white cell count, after the administration of BAL and, in one or two cases, the very dramatic increase immediately after, strongly suggests that the return of the white count to normal in these oases of agranulocytosis was related to the fact that BAL had promoted the excretion of arsenic. In the oases receiving massive doses of mapharsen in error, we had several experiences. One case began pleasantly enough. The physician in charge of the clinic happened to be with me in Wash ington. His clinic was in the far west, and he received a telegram that, by mistake, the patient bad received 1200 mg. of mapharsen. He wired back, "Give him BAL." The patient was given two or three in jections of BAL and felt so much better that BAL was discontinued, whereupon the patient went on to develop acute atrophy of the liver in twelve days. Ob viously you cannot expect 1200 mg. of arsenic to be detoxified by two or three injections of BAL, amounting, in sum total, to 200 or 300 mg. of BAL, most of which is rapidly excreted. As a result of our experience in these 227 oases it was recommended to the armed forces that, in cases of toxic re actions to arsenic, however encountered, if the reactions were severe, [e.g. a se vere dermatitis or toxic encephalopathy] treatment with BAL be given around the clock, every four hours, for at least two days, at A dosage of 2Vk mg. per kilogram. In a man of 70 kilograms, this is 175 mg., or approximately 2 cc. of the 10 percent solution per injection. At the end of those two days, if the patient was obviously better, the number of injections per day could be reduced from a total of six to something like two to four, and eventually discontinued completely after seven to ten days. It was natural to attempt to extend these observations with arsenic to other heavy metals which, like arsenic, have ability to react with sulfhydryl groups. In experiments on antimony poison ing, for example. Fig. 5, it was shown that in rabbits which had been poisoned DUP050314444 BAL 89 with a variety of antimonials BAL regu larly had the same striking effect on the urinary excretion of antimony as it had in arsenic poisoning. The effects on survival, although not quite as dramatic, were nevertheless real. In animals which had received large amounts of arsenical, between 1 and 1.2 times the lethal dose and, in several instances, three or four times the lethal dose, we were able to protect, in some instances, 75, in others 91, and others only 50 percent of all the ani mals which had adequate treatment with BAL. Our group did not study the effect of BAL in gold poisoning. Those of you who have been following the literature will, however, have seen case reports of patients with dermatitis resulting from the use of the gold salts in the treatment of arthritis. Although there is by no means unanimity of opinion, there is the consensus among those who have used the drug that it has definitely shortened the time of recovery. In mercury poisoning. Dr. Longcope, Dr. Luetscher, and their associates have had what appear at the moment to have been extraordinarily favorable results with the use of BAL. I do not have to tell this group how difficult it is to evaluate results in mercury poisoning. Some patients who get minimal amounts die, and others who get classical amounts of mercury may recover. The definite evaluation of the effects of any thera peutic agent in mercury poisoning will require the slow and laborious accumu lation of data. There is, however, good reason to believe, on the basis of the data already in hand, BAL will prove highly effective in the treatment of mer cury poisoning. A curious incident developed early in the application of BAL to the use in mercury poisoning. In normal subjects, as soon as one exceeds a dosage of 2 mg. per kilogram, one begins to run into toxic reactions. In these mercurypoisoned patients, however. Dr. Longcope and his associates found they could give 3, 4. and 5 mg. per kilo and have no trouble whatsoever. That was Fig. 5--The effect of BAL on the urinary ex cretion of antimony. The experimental data, plotted on a percentage basis, refer to the twohour period immediately preceding the injec tion of BAL as 100. The symbols have the same significance as in Fig. 1. DUP050314445 90 EAGLE Fig. 6--The effect of BAL on the urinary excretion of lead, plotted on a logarithmic scale. puzzling until it was realized that, in these patients who have taken large amounts of mercury, there is enough mercury in the body so that not only does the BAL detoxify the mercury, but the mercury also detoxifies the BAL. Otherwise toxic amounts of BAL com bine with enough mercury in vivo so as to reduce the immediate toxic reac tion to the BAL. My ostensible reason for being here today is to talk about lead poisoning. Dr. Germuth and I did some work with rabbits which was reported last year. I will say immediately that 1 feel as strongly as some of you that, to para phrase Gertrude Stein, a rabbit is a rab bit is a rabbit, and that it is dangerous and, indeed, impossible to extrapolate data from animals to man. The animal data can only suggest lines of attack, the ultimate answer to which is always the human trial. With that necessary reservation, in DU P050314446 Fig. 7--The effect of multiple injections of BAL on the urinary excretion of lead in animals with a subcutaneous deposit of lead acetate. animals which were poisoned with lead acetate, by a method which has abso lutely no analogy to any type of lead poisoning one encounters in man, BAL had a striking effect in accelerating the urinary excretion of lead. Animals were given subcutaneous in jections of lead acetate in truly heroic doses. In these doses the lead is not absorbed but establishes a local depot of lead, from which it is slowly ab sorbed, and the animal dies in the fol lowing weeks. It is thus a subacute type of lead poisoning. In such animals, the injection of BAL does have a striking effect in promoting the mobilization and excretion of lead. I would like to point out that Fig. 6 is a logarithmic scale, so the differences are even more pronounced than they appear to be at first glance. In this chart the results have been ex pressed on a percentage basis. One hundred is the average excretion of lead in these animals immediately prior to the injection of the BAL. As you will see, for the first two hours after the in jection of the BAL in the animals, the rate of excretion was increased from ten- to fiftyfold. As has been regularly ob served, whether with arsenic or anti mony, and reflecting the pharmacology of BAL, the effect then fell off sharply in the following two hours, so that be tween the fourth and sixth hour the rate of excretion was only slightly greater than in the pre-BAL control period. DUP050314447 92 F.AGLE I should say, also, that, although BAL did have this striking effect in promot ing excretion, it did not promote the survival of these animals. Fig. 7 shows the effect of repeated in jections of BAL. As one continues to give BAL, what one gets back each time progressively . diminishes. Apparently the first few injections of BAL permit the animal to excrete the lead which is readily mobilized, and has no effect on some of the massive depots from which the lead can be mobilized only with difficulty. Just where those readily mo bilized depots may be, we do not know. In these animals receiving massive amounts of lead acetate and, also, in animals which had been acutely poi soned by the intravenous injection of lead acetate, BAL had no effect on sur vival. In one experiment which we have not been able to duplicate, BAL actually seemed to accelerate the death of the lead-poisoned animals. In spite of that, I would like to read the last paragraph of our original paper. "It is clear that, under the conditions of the present experiments, BAL had no demonstrable protective action and, at times, actually accelerated the toxic ef fects of lead acetate in rabbits. The data offer no reason to believe that BAL would prove of value in the treatment of lead poisoning in man. "Nevertheless, the experimental lead poisoning produced in rabbits by either the subcutaneous or intravenous injec tion of lead acetate differs so materially from that seen in man, both with respect to the route of administration, the chem ical form of lead, the chronicity of the intoxication and the organs which are affected, that the results obtained with BAL in these experimental animals had no necessary significance with respect to possible therapeutic activity in man. "Despite the' present failure of BAL to detoxify lead in rabbits, its effect on the excretion of lead was so striking as, perhaps, to justify its cautious thera peutic trial in human cases." That expresses my purpose in being here this morning. There are enough data now with respect to the treatment with BAL of cases of arsenic, gold, antimony and mercury poisoning, to suggest that, in those types of poison ing, it has a definite therapeutic action. The toxic reactions from the BAL have been minimal except for the occa sional and transitory local reaction at the site of the injection. 1 submit that it may, perhaps, be worth while to try BAL cautiously in the treatment of lead poisoning with adequate controls with respect to its effect on excretion, its effect on the blood concentration of lead, on stippling, and so on. I would not be surprised if it were wholly ineffective, but I think it deserves trial. I would like to submit for your con sideration, also, the possibility that a single injection of BAL, given once or twice a week, to those of your men who are most acutely exposed, might permit the excretion of enough lead to put off, for a long time, the accumulation of enough lead in the body to cause toxic symptoms. I wish to suggest, also, that, although BAL has proved so effective in the treat ment of certain types of heavy metal poisoning, there is no reason to believe that other compounds may not be de veloped which are even more effective, and which, acting on the same principle as BAL may serve to abstract lead from its combination with tissues. Ch a ir ma n Bo w d it c h : The discussion of Dr. Eagle's paper will be opened by the professor of chemistry at Johns Hop kins University, who has led an exten- ' sive research project in deleading and, with his colleagues, has devised a new chemical substance for this purpose. Dr. Alsoph H. Corwin. BAL 93 DISCUSSION Dr . Al s o p h H. Co r w in [Johns Hop kins University, Baltimore, MdL]: I think Dr. Eagle's cautious optimism in the case of BAL--or should I say conserva tive recommendations--are entirely jus tified. I, for one, would be most happy to see some clinical trials of the sort he suggests, carried out with BAL. However, I want to direct attention to a slightly different matter in connec tion with these studies. Dr. Eagle's paper has emphasized the differences between various metals in their poisoning effects, and, particularly, in their resistance to antidotes. This suggests that, in the elaboration of new antidotes, differences between the various metals must be emphasized so that the chemist can take advantage of the chemical differences in order to get effective agents for the treatment of poisoning. If you read the paper of Peters, Stocke and Thompson, you obtain the concept that there will be a limited number of types of compounds which should be effective in the treatment of heavy metal poisoning. The reasoning seems tight; it seems hard to find a way through it to a new type of compound. But our examination of this subject has led us to believe that the reasoning is not quite as tight as might seem on the first examination, and that there are ways through to the development of other compounds which may be more effective for certain metals. One suggestion which came to us is the known affinity of dithizone for lead. Dithizone is used analytically in the determination of lead, and it will not combine with arsenic at all; neither will it combine with antimony. So, here we have a practical suggestion of a marked chemical difference between lead, in its reaction to a possible antidote, and arsenic, in its reaction to a possible antidote. I want to suggest to you, briefly, how a chemist might go at the job of con structing an antidote for heavy metal poisoning. The accompanying photo graphs, which are cartoons, will give you an idea of what Dr. Eagle has pre sented in much more formal fashion for you. Fig. 1--This suggests how a sulfhydryl enzyme may act in the body. I do not want you to interpret this too literally, naturally. I do not wish even to suggest that all sulfhydryl enzymes act similarly. Here we have our sulfhydryl enzyme, with his two hands, and here we have a sugar molecule. You see he is nice Figs. 1 & 2. m DUP050314449 94 DISCUSSION Figs. 3, 4, 5 & 6 (from top to bottom). and fat. The sulfhydryl enzyme reduces the sugar molecule and, in that, per forms a necessary metabolic function. Fig. 2--The enzyme then has ex hausted its potentialities momentarily, and needs a helping hand from some thing else. It gets this from traveling glutathione in the blood or, perhaps, some other source of sulfhydryl which performs an exchange, reactivates the enzyme for further work, and is prop erly punished for putting its fingers into other people's business. [Laughter] Fig. 3--This gives you a concept of how poisoning with a heavy metal-- in this case I have chosen mercury, mercury chloride--may work on the enzyme. Here is the enzyme ready to go to work on the sugar, but mercury comes along instead, and the enzyme is taken out of action, at least momentarily, by the mercury. Fig. 4--BAL, as we have had pointed out, is effective in mercury poisoning. It takes the load off the enzyme which we thought originally was dead, but we have found now that, instead of being dead, the enzyme was only stunned and could be revived. You see the hydrogens are here, on the sulfhydryl compounds, ready to attack the sugar again, and the BAL carries off the load of mercury. Apparently it does not like it too much. [Laughter] Fig. 5--This shows dithizone. As you know, it is a red dye. We thought it would be interesting to represent it by an Indian. The chemical process of activation of these materials for metals probably involves polarization. It was our feeling that, if you could get materials which were strongly enough polarized, you would have at least one of the items necessary to bring about greater affinity of these substances for heavy metals. DUP050314450 BAL 95 of tlie dithizone molecule. We obtained a reasonably water-soluble compound which had, to us, quite surprising properties. In the first place, I would like to em phasize some of the disadvantages of BAL. First is the odor that Dr. Eagle has so graphically pointed out. The ma terial can be smelled a mile away. Sec ond, the relative toxicity. Approximate ly 2% to 3 mg. per kilo can be given without discomfort. The substance we have worked with has no odor at all. It substitutes for odor, color. The animals and people ^ This is a cartoon, and I have emphasized that have taken the substance turn up one of lire properties of the substance with bright red urine. It is an orange to the exclusion of others. But, you see, red, so it is distinguishable from blood, in this process of activation, I have got but people are not always too careful a negative sulfur here; this is a minus about this distinction. ,, charge and there is a positive charge This solubilized dithizone has been down at the other hand. In this polari given parenterally at the rate of 400 mg. zation process, the material is ready for per kilogram per day over a period of attack on the heavy metal, so the ma four weeks, without any detectable signs terial which can be polarized should be of intoxication. most effective as an antidote. In a "tour de force," we brought up We feel that dithizone may have its a litter of mice that had never had any advantages over BAL because the ma drinking water. Their water was always terial has a more negative sulfur, a more contaminated with this material to the vigorously attacking sulfur than BAL extent of 2,500^ mg. per kilogram per does. day. That is 2% gm. per kilo per day, Fig. 6--This shows you the inacti throughout their lives. They never had vated enzyme, again, properly stunned, white water to drink. This red water and the Indians go after the mercury. seemed to satisfy them perfectly well, Fig. 7--This shows you they have, and they brought normal litters, and the just like the BAL, taken their load off litters were brought up with red water the enzyme and revived it for future instead of white water, and they had activity. normal litters. At that time we discon That is enough fantasy in the matter. tinued the experiment, but we do not I would like to report a few factual believe any .cumulative effects of this results. Dithizone, itself, is too insoluble substance will probably be found. Two to be effective in applications of this percent solutions are not irritating to sort It is necessary, first, in order to the eye. get an effective material, to make it The disadvantages of the soluble di water-soluble. This water solubility can thizone are first, its high cost. We did be obtained in a number of ways chemi one rabbit experiment with the material. cally. The way we chose was to put car All the rest of our work has been done boxyl groups on in the desired positions with mice. The reason is that it took DUP050314451 96 DISCUSSION ns about four months to accumulate enough substance to do the one rabbit experiment. This is something which can be solved later, as Dr. Eagle has suggested to me privately. It might be possible to get somebody to work this synthesis in large kettles instead of smaller pots of the sort we use in the chemistry laboratory. But we have at tacked the problem from another direc tion. We have attempted to improve the synthesis and believe that the next time we need more of the material, it will not be quite as difficult to procure. It has another disadvantage, and that is its lack of stability to air. The pow der keeps quite well. The water solu tions must be stored under' nitrogen in order to have them keep, and we are not quite sure they keep perfectly under these conditions, but they certainly keep longer under nitrogen than they do in air. Hence, in our experimental work we always use freshly prepared solu tions. This substance was first developed for cadmium poisoning; later for lead poisoning. It seems to work well against cadmium. There is no difficulty at all in converting a dose, which is 100 per cent lethal, of cadmium to a dose which has no lethal effects at all. It is a 100:0 ratio. We can save all animals that are poisoned with a lethal dose of cadmium. However, the cadmium problem is es sentially easier than the lead problem., because an animal that has a lethal dose of lead has many, many times the amount of metal in its body than the animal that has the lethal.dose of cad mium. The result is that in lead poison ing a tremendous volume of material must be moved. Acute lethal lead poisoning is quite different from the type of lead poisoning that was discussed yesterday. Acute lethal lead poisoning has as one of its manifestations kidney block. It also has the lead colic that.you see in people, and severe intestinal involvement is certainly present. So, we have both the kidneys and the intestines to look after. In animals that have been killed with a lethal dose, you will find hemorrhages. These can be entirely controlled with the soluble dithizone derivative, in a man ner which I suggest would be useful in human cases, even when the colic has been properly controlled with calcium. We use colonic irrigations on animals that have had lethal doses of lead. We can bring them to autopsy then and find no hemorrhages. So, again, we have an effect of all or none. The antidote then is capable, when brought into contact with the intestinal mucosa, of preventing intestinal dam age. The kidney block, however, is much more difficult. I want to say that, in the human cases of lead poisoning, it seems to me quite probable that, even after the colic is controlled and the pain has disappeared, there may be intoxication from lead absorption, from the intestines, and damage to the intestines. So, it seems to me entirely warranted to try colonic irrigations with an antidote, as distinct from colonic irrigations without an antidote. The kidney block is a much more dif ficult problem. Once an animal's kidney is blocked, it is hopeless, in our experi ence, to try to revive it. Kidney block takes place, sometime, fairly early in the stages of poisoning. We believe this is one of the reasons why late antidote use is not effective, while early antidote use may be effective. However, there are apparently two kinds of kidney block. One, interference with the enzymatic work of the kidney which normally permits excretion to go forward. This is the normal type of kidney block you get in heavy metal poisonings of all kinds. The kidney DUP050314452 BAL 97 ceases to function, but you do not nec lethal lead poisoning which occasionally essarily get a precipitate backing up be occurs. hind the excretory organ. Ch a ir ma n Bo w d it c h : This subject is However, in these antidote treatments, now open for brief discussion. .you see another kind of kidney block. Dr . Go r d o n C. Ha r r o l d [Detroit, This is a mechanical kidney block due Mich. ]: I would like to ask whether or to the limited solubility of the metal not it would be possible to take this antidote complex, and apparently it is insoluble compound and add some ma not due to poisoning, although it is very terials that would gradually release this difficult to be certain of this matter. very insoluble material, so you could But in the case of cadmium poisoning slowly eliminate that block. we have been able to take certain steps Dr . Co r w in : All I could say to that which will help start kidney action is that we have tried but have not been again, and, on doing this, the block is successful. Apparently what happens is removed and the kidney seemed to func that this material, like BAL, mobilizes tion quite normally. I believe that this the lead, and, once you get the block is possible in the lead cases, too. formed, more and more of the substance In the lead cases, the amount of ma pours into the kidney. The thing you terial that has to be handled by the kid have to do is to keep the block from ney, as I say, is approximately 50 times forming, or else remove it in the early as great as it is in the cadmium cases, stages by flooding the kidneys. We have so that the possibility of mechanical not been able to do anything besides blocking of the kidney is much greater. flood the kidneys to get the block to We fmd that the administration of a move. large amount of physiological salt solu Dr . D. J. La u e r [Kettering Labora tion is the best method for unstopping tory, University of Cincinnati, Cincin the kidney; that is the best we have been nati, Ohio]: I enjoyed very much the able to find so far. interesting, lucid discussion this morn Under these conditions, the kidney is ing on BAL by both Dr. Eagle and Dr. opened up, and a lot more of the heavy Corwin. metal is eliminated. I do not feel that I would briefly like to present some we yet have the answer in lead poison observations made by Dr. Henry Ryder ing. I think that a certain amount of and others of the stall of the Kettering optimism is in order. I think, perhaps, Laboratory, relating to the use of BAL we are on the right track. in cases of human lead poisoning, a We are able with this antidote, and preliminary report of which was pub in the case of mice only --- I must under lished in Science, July 18, 1947, by line again -- we are able to increase the Ryder, Cholak and Kehoe. Two groups survival time of all animals. We are not of patients, all ill with acute lead poison able to save all animals. We hope that ing, were studied. by improved techniques of administra There was no evidence that the two tion we may be able to save all animals groups of men were from populations from lethal doses of lead. We certainly with different attributes. The type, dura feel that we have here a substance which tion, intensity and multiplicity of symp warrants further investigation in the toms were similar in the two groups. control of colic, in the speeding up of There were 11 in one group and 16 in recovery from metal poisoning, and per the control group. These people were haps even in the treatment of acute all hospitalized. -* DUP050314453 98 DISCUSSION Treatment with dithiopropanol was individualized, and usually given in each phase to the limit of tolerance. The first patient was given 5 mg. per kilo immediately, and 2% mg. per kilo every four hours, for eleven doses. -Therapy was discontinued because of hyperten sion, severe joint and muscle pains, or subsidence of colic. In later cases it was attempted to give more dithiopropanol by less frequent injections over a longer period of time. This was unsuccessful. The average patient was treated three days and given 1.7 gm. of dithiopropanol. Some patients appeared to be better and some worse, following the administra tion of BAL. It seemed apjoarent that the drug had no immediate spasmolytic effect. The time at which colic or pain re mained persistently absent appeared not to be influenced by the administration of BAL. Persistent weakness was present, uniformly, after the disappearance of pain. Men treated with dithiopropanol did not recover and return to work more promptly than did those untreated. From the clinical viewpoint, then, the use of BAL was without beneficial effects. There was, however, a characteristic and dramatic effect upon the lead metab olism. The lead concentration in the urine increased from five- to fifty-fold with the greatest relative increase in the men that had not been exposed ab normally to lead. The effect on the blood lead concentration was immediate and in the reverse direction from that of the urine. By seven and one-half minutes the blood lead concentration was falling rapidly and it continued to fall, but with diminishing rapidity, the maximum fall being reached between one and eight hours. Gradually there was a return in the lead concentrations in both blood and urine to levels approximating those observed before the administration of BAL. The plasma and fecal lead concentra tions were unchanged by the therapy. The total amount of lead eliminated from the body by a single injection did not exceed 1 mg. and was usually a few tenths of a milligram. In summary, it has been observed that dithiopropanol causes a prompt drop in erythrocyte lead concentration and an immediate rise in the urine lead concentration to a degree far greater than that observed following any other type of therapy tested. It has also been observed that the drug has no spasmolytic effect and does not shorten the course of the spontane ously reversible condition, lead colic. It is, therefore, inferred that the me chanism of intoxication and the mecha nism of storage and elimination of lead are not intimately related. The observed effects on lead metabo lism are consistent with the hypothesis that lead combines with some erythro cyte component and that this combina tion can be partially reversed in vivo by BAL therapy, but the failure of symp tomatic response to therapy gives no support to the theory that an enzyme system dependent on thiol groups for its activity is involved in the mechanism of lead poisoning. The data of these studies will be pub lished by these men in detail soon. I am now interested, under the stim ulus of Dr. Eagle, in using BAL prophylactically. About three weeks ago I took two men of the same age, the same race and the same length of exposure, doing identically the same job, on a- reverbera tory furnace. One works from midnight to eight in the morning, and the other takes over from eight in the morning until four in the afternoon. Their urinary and blood lead levels J.k*. DUP05031 4454 BAL 99 are about the same; their stipple count about the same; and their state of health about the same. I ran a control period on them for about a week. Then, one I gave 2 mg. per kilo of BAL, and the other one I gave an equivalent volume of liver ex tract. These data have* not been avail able for study and, therefore, they may not be introduced into the record at this time. Thank you for this opportunity. Ch a ir ma n Bo w d it c h : We are ap parently faced with a new unit of mea surement. Did I understand Dr. Lauer to refer to 2 mg. per "Kehoe?" [Laugh ter J Is there any further discussion of this very interesting subject? Dr . Wil l ia m C. Wil e n t z [National Lead Co., Perth Amboy, N. J.]: This is the first time I have ever heard this discussion on BAL. So, it strikes me as a most interesting thing. I would like Lo tell Dr. Eagle some thing along this line; I noticed, in the treatment of these animals, you injected them when they were acutely poisoned. You know, in lead poisoning, most men do not approve of such dramatic things, even the men who advocate deleading. They wait until the acute phase is over. So, there is some difference. I am curious to see what is going to happen in the long run. In other words, should these men, in trying their experi ments on the human, employ BAL dur ing the acute stage of human lead poi soning? Where are they going to be if they do not give it during the acute stage? In other words, will it be safe lo give BAL during acute stage or in chronic stage as a deleading agent? I would welcome some advice along these lines so we could help establish the value of BAL in the human lead intoxi cation cases. Dr . El s t o n L. Be l k n a p [Globe- Union, Inc., Milwaukee, Wis.]: I wish to ask Dr. Eagle a couple of questions. There have been noted in the literature some side effects, with the use of BAL notably that it inactivates insulin or the production of insulin, perhaps, and the action of insulin as an enzyme. If so, would there be any permanent effect on that mechanism? Also, does Dr. Eagle see any reason why procaine should not be combined with the BAL, because it is an extremely painful pro cedure to have that given, as 1 have observed, and I wonder too, if the use of procaine would either decrease the effectiveness of the BAL or otherwise make it dangerous to use? Then I would like to know what he thinks of the fact that has been noted in the literature that the BAL and cad mium end-product is toxic to the kidney tissue. Ch a ir ma n Bo w d it c h : Will you re spond, Dr. Eagle? Dr . Ea g l e : I would like to make it clear that I am not here to recommend anything, and that I am not a proponent of any particular method of treatment. The only point I am trying to make is that, in support of Dr. Corwin, it seems to me that the last word has cer tainly not been said on the treatment of lead poisoning. Everything we have observed in other types of poisoning indicates that the earlier treatment with BAL is begun, the better. If it were to be effective, one might suppose it would be most effective in the acute stages. On the other hand, there is very little in the animal data to indicate that BAL is going to be dra matically effective in the treatment of lead poisoning. I think that studies such as those of Dr. Lauer ought to be carried on, perhaps on an even larger scale, in order to establish once and for all what BAL can or cannot do in the treatment of lead poisoning. ) DUP050314455 100 DISCUSSION The other aspect of the problem is, will BAL have any effect in the preven tion of lead poisoning? Can one, by pulling out a fraction of a milligram of lead once or twice a week from whatever focus it can be mobilized, effectively delay the onset of symptoms in a large number of men? 6 Dr. Lauer's attempt with these two men is laudable. I think it ought to be increased tenfold and a hundredfold, to get data of statistical significance. But the last and most important point is the report of Dr. Corwin. There are, I think, enough data in hand to indicate that one can develop compounds with specific affinities for heavy metals, and with relatively minor toxicities for the host. I think it is in the development of such compounds, almost certainly not BAL, hut compounds which, like BAT., have a specific affinity for heavy metal and relatively minor affinity for the host tissues -- it is in the development of such compounds that we have the best hope for the successful treatment of lead poisoning. As to the question concerning the local reaction to BAL, in preliminary trials I think the men should be fore warned that the injection is going to hurt somewhat and they may have local pain for fifteen minutes or half an hour after the injection. In my experience at least, they do not mind it. The incorporalion of 20 percent benzylbenzoate in the peanut oil solution has done a great deal to cut down the local reac tion. I cannot believe that procaine would have any chemical effect or pharmacological effect on the activity of the BAL, and it perhaps could he tried. Although it is true that BAL added directly to insulin does have an effect, we have seen no significant effect on blood sugar in the patients which have been studied from that point of view. If it. had had an effect, I think it would have developed in the many hundreds of patients who have been treated with BAL for various types of arsenic poi soning. As to cadmium poisoning, there is some evidence that, although BAL ef fectively mobilizes cadmium, that mo bilized cadmium is toxic to the kidney. So far at least, we have seen no evi dence in man of this possible toxic ef fect of BAL in cases of lead poisoning. Nevertheless, I again would suggest caution in its use. There was a case of lead poisoning treated by Dr. Robert Austrian in the Johns Hopkins Hospital while I was there. In this case, as Dr. Ryder and his associates did in their series, we observed a striking effect on lead excretion. The man recovered un eventfully; but he may have recovered anyway. It will take just the type of study Dr. Lauer has undertaken in the two cases he described, on a much larger scale, to evaluate BAL or any other agent suggested for the treatment of lead poisoning. Dr . Be l k n a p : If the doses as reported by Dr. Lauer were a shade too heavy, that might have accounted for some of the symptoms. Dr . Ea g l e: Yes, I think they were. They exceeded anything we have dared to use even in our treatment of severe arsenic poisoning. In mercury poison ing, there is a mutual detoxification. If one is going to try this in lead cases, I would recommend injections of the 10 percent solution at a dosage of 2.5 mg. per kilogram at four-hour intervals, repeated four times a day. This brings the treatment within the compass of a twelve-hour day. I would suggest no more than that in treatment, continued for two to four days, and then slope off to about two a day. If any of those present are going to try BAL for the prevention of lead poi soning, and if you can get the coopera- DUP050314456 w BAL j' JT >; | t ij r'fvPi!! tion of your men [and that is difficult] I would suggest one or two injections a week, again at a dosage of mg, per kilogram. In a man weighing 75 kilos (165 pounds) this represents 1.9 cc. of the 10 percent solution. Ch a ir ma n Bo w d it c h : Our next paper will be by a man who was associated with the University of Illinois in fuel utilization for the Geological Survey prior to the war. During the war he was head of the Coal Division of the Bureau of Mines, and, in that connec tion, became interested in our present subject while in the Ruhr. He is now director of the Air Pollution Control District of Los Angeles County, Cali fornia. Dr. Louis C. McCabe will speak on "Air Pollution Control Regulations in Los Angeles County." iip * I REFERENCES The Systemic Treatment of Arsenic Poi soning with BAL (2, 3-Dimercaptopropanol). Ven. DU Inf. 27: 114, May 1946. Harry Eagle. Clinical Uses of 2, 3-Dimercaptopropanol (BAL). I. The Systemic Treatment of Experimental Arsenic Poisoning (Mapharsen, Lewisite, Phenylarsenoxide) with BAL. /. of Clin. Inv. XXV: 451-466, July 1946. Harry Eagle, Harold J. Magnuson and Ralph Fleischman. The Protective Action of BAL in Experi mental Antimony Poisoning. J. Pharmacol, and Exp. Therap., 89: 196-204, Feb. 1947. Harry Eagle, Frederick G. Germuth, Jr., Harold J. Magnuson, and Ralph Fleischman. The Effect of BAL on the Excretion of Arsenic in Arsenical Intoxication. }. Clin. Inv. XXV: 534-40, July 1946. J. A. Luetseher, Jr., Harry Eagle, and W. T. Longcope. The Systemic Treatment of 227 Cases of Arsenic Poisoning (Encephalitis, Dermatitis, Blood Dyscrasias, Jaundice, Fever) with 2, 3Dimercaptopropanol (BAL). Am. 1. Syph., Gonor., and Ven. Dis. 30: 420-441, Sept. 1946. Harry Eagle and Harold J. Magnuson. The Efficacy of BAL (2, 3-Dimercaptopro panol) in the Treatment of Experimental Lead Poisoning in Rabbits. J. Pharmacol, and Exp. Therap. 92 : 397-410, April 1948. Frederick G. Germuth, Jr,, Harry Eagle and with the technical assistance of Jean C. Grossberg. my A n&:v.-.I' ' -fr.t... ( DUP050314457 AIR POLLUTION REGULATIONS IN LOS ANGELES COUNTY By LOUIS C. McCABE, Ph.D. Director, Los Angeles County Air Pollution Control District, Los Angeles, Calif. Los Angeles has experienced an in creasing nuisance from atmospheric con tamination by fumes, gases and dusts in recent years. The term "smog" has been applied to this complex of atmos pheric contamination which frequently limits visibility to a few blocks and causes eye, nose, and throat irritation. It attained objectionable proportions in the early years of the war, and, in response to public demand, the 1947 session of the California legislature added comprehensive statutes to the Health and Safety Code, namely Chap ter 2, Division 20, for the purpose of controlling it. The Act recognizes that the problem is broader than "smoke abatement" and provides that the Board of Supervisors of any county on finding that serious "air pollution" exists, may establish a county-wide district to con trol it and may pass such supplementary regulations as are required. Topography and meteorological con ditions aggravate the effects of air pollu tion1 in the Los Angeles Basin. High mountain ranges surround it on three sides. Prevailing winds during most of the year are westerly or southwesterly during the daytime while their average velocity is only slightly more than six miles per hour on a 24-hour basis. These on-shore "sea breezes" move gently over the area from 8:30 in the morning until midnight During the night a light land breeze develops which moves down the mountain valleys toward the sea-coast at an average of about one mile per hour. In the sum mer and early fall, temperature inver sion limits the vertical distribution of the atmospheric pollution as the local winds move it over the area from the west during the day. If pollution does not escape through the mountain passes during the day, it returns on the night breeze to be reinforced by the next day's contamination. The inversion layer is very resistant to turbulence and holds the pollution near the ground. Visibility is greatly restricted at times of low inversion. In Los Angeles County, essentially no coal is burned and air pollution from improper oil firing is comparatively rare. The great majority of the air pol lution problems that are encountered stem from emissions that are a func tional part of the plant operation, and careful operation and design cannot al ways prevent these emissions. Frequent ly, the only way they can be prevented is by the addition to the plant of me chanical equipment designed to remove the emissions. Most of the dusts and mists we would control are less than one micron (1/25,000 in.) in size. This is largely a new and untried field of con trol in this area. Dust particles larger than ten microns are relatively easy to remove from effluent gases2. It is these particles that deposit under normal meteorological conditions within five or ten miles of their origin and are prob ably responsible for most of the dust precipitated over the city. Improved cyclones may be used with the expendi ture of a large amount of power to re cover dust down to five microns in diameter. Between one and five microns, various types of water scrubbers can be used. Below one micron, the dust parti cles are most effective in scattering light and, therefore, are responsible for low visibility. These particles do not settle but remain suspended unless they are washed out by rain. They are effectively removed at the point of origin by the 102 DUP050314458 AIR POLLUTION 103 electrostatic precipitator, fine fiber, or thick sand filters or the Venturi scrub ber. The rules and regulations of the Dis trict which affect the metallurgical in dustries are briefly summarized as follows: 1. RINGELMANN CHART. A person shall not discharge into the atmos phere from any single source of emission any air contaminant for a period or periods aggregating more than three minutes in any one hour, which is (a) As dark or darker in shade as that designated as No. 2 on the Ringelmann chart, as published by the United States Bureau of Mines, or (b) Of such opacity as to obscure an observer's view to a degree equal to or greater than does smoke described in subsection (a) of this rule. 2. PARTICULATE MATTER. A per son shall not discharge into the at mosphere any dust, ashes, charred paper, soot, grime, carbon, or other particulate matter exceeding 0.40 grains per cubic foot at the point of discharge into the atmosphere. 3. SPECIFIC CONTAMINANTS. A person shall not discharge into the atmosphere any one or more of the following contaminants, in any state, or any combination thereof exceed ing in concentration at the point of discharge: Lead......................... 0.035 grains per cubic foot Zinc oxide............... 0.035 grains per cubic foot Sulfur compounds.. 0.2 percent by volume (calculated as SO?) Fourteen industrial groups have com pleted or are in the process of studying their specific air pollution problems. This paper is concerned primarily with the investigations and findings of the non-ferrous founders, the gray iron founders, and the two open hearth steel plants of the area. The writer has drawn heavily on reports on the nature and quantity of contaminants furnished the District by these three groups. The non-ferrous founders employed six consulting engineering organizations or laboratories in Los Angeles to make a series of 16 tests on six representative types of equipment in use by the nonferrous founders for eight different al loys. The factors evaluated in the survey were: (a) Type of furnace. (b) Maximum and average concentra tions, and the variation of concen tration during the melting cycle, of both fume and other particulate matter. (c) Type of fuel used,-- oil, gas or electricity -- and fuel-air ratios. (d) Composition of the alloy. The investigators found it necessary to establish a procedure for field sam pling and laboratory analysis. The sur vey of representative foundries showed that in many cases the products of com bustion and the material volatilized from the furnaces are discharged directly into the air without any specific exhaust sys tem. In some cases, hoods and exhaust stacks were already installed but in gen eral they depend on gravity circulation for exhausting the system. The temper ature of the gases discharged from the furnaces range between 2,500 and 3,500 degrees Fahrenheit, and are diluted by a considerable amount of secondary air on entering the stack. Direct sampling of gases was not feasible at the furnace temperatures obtaining, and where ex haust systems were not already pro vided, a portable hood, stack and blower was used for measurement of air flow and for obtaining samples for analysis (Fig. 1). DUP050314459 104 McCABE The following conclusions for general operating conditions and procedures are drawn from Table I. The average loss due to volatilization and recondensation for average brass foundries and smelting operations is approximately constant -- in the neighborhood of one percent of the total melt charged. A loss of this magnitude for these operations will re sult in violation of our present regula tions. Foundries handling copper-lead, magnesium, aluminum, and high nickelbrass alloys, however, will be within the legal limits of emissions, providing good foundry practices are followed in all operations. It is estimated that in addition to the cost of hoods and stacks, the installation of equipment for removal of fumes from the stack gases will cost between $2,000 and $20,000 per furnace exclusive of operating and maintenance cost. The average particle size of zinc fume is less than one-half micron. In high concentrations, the fume may agglom erate into large particles, but at other times the particles remain discrete. The small particle size precludes the use of cyclones. The non-ferrous foundry re port summarizes three general types which may be applied to their installa tions at. reasonable expense: 1. Fabric filters (bag houses) are prob ably the most efficient of the three types and, where cooling flues are required, will probably be the high est in first cost of installation. Bag houses may be either automatic or manually operated. 2. Mechanical scrubbers are available in a wide range of sizes and types with auxiliary equipment of many different kinds to meet special con ditions. Generally speaking, the me chanical scrubber would not be as efficient as the bag house on foundry Fig. 1--Diagramatic sketch of sampling layout for typical brass furnace. DUP050314460 AIR POLLUTION 105 TABLE 1 Significant Data for Loss Calculations Non-Ferrous Industry Type Stack Loading Average at 6G*F,, Wt. of Melt Total Loss Time of Melt Effluent Melt Disch urge Ratio at 60F. fellow Brass Medium. Melt Avc. of 2 tests Red Brass Medium Melt Ave. of 2 tests Red Brass Heavy Melt Ave. of 2 tests Brass Smelting 1 teat 0.428 gr./cu. ft. 0.252 gr./cu. ft. 0.409 gr./cu. ft. 0.39 gr./cti, ft. 800 lb. 1.31 %-- 10.47 lb. 50--ioo min. 00 lb. 3.01 % -- 6.001b. n in in. 3650 lb. 0.985%-- 36.0 lb. 25 tons 1.26 %--629.0 lb. 161 min. 25 hr. 99% ZnO 215 cu. ft./lb. 90% Zu 282 cu. ft./lb. 169 cu. ft./lb. 226 cu. ft./lb. Copper-lead, magnesium, aluminum, and bigh nickel-brne alloys will give low discharges and Total losses of less than 0.2% (.002). emissions. The overall cost, for equivalent volumes would generally be lower than for a bag house. 3. Packed tower. This type of collec tion equipment is generally adapted to handling large volumes of gas, carrying relatively low concentra tions of solids. Their efficiency is generally lower. The first cost of the installation for equivalent vol umes, is usually lower than fabric filters. This type of equipment is generally used for fine dust in rela tively low concentrations, and the successful application of packed towers to foundry gases will depend upon the effectiveness of "wetting agents." Three pilot installations are now un dergoing test by the Non-ferrous Found ers Association for the purpose of de termining recoveries and operating costs. The results of these pilot opera tions will enable each operator to de- TABLE II Significant Data for Loss Calculations Ferrous Industry Type Gray Iron Light Melt Medium Melt 1 test Stuck Loading Wt. of Melt Total Loss Time of Melt 1.604 gr./cu, ft. 6.17 tons 0.748%-- 92.1 lb. 1.1 gr./cu. ft. 17.0 tons 1.45 %--S08 lb. 80 min. 156 min. Heavy Melt 1 test 0.798 gr./cu. ft. Steel Open Hearth 2 tests 0.79--0.86 gr./cu. ft. 50.4 tons 0.564%--570 3b. 5 hT. 20 min, 7 to 5 ton9/hr. 0.63 to 0.65 8% to 10% hr. 726 to 667 lb. Mean particle size. 0.25 microns No particle above 3 microns Opacity in excess of 40% during majority of melt Effluent to Melt Ratio Discharge 32.5 cu. ft./lb. 91.5 cu. ft./lb. Lead and ZnO 5% each Silicon Oxide 30% Iron Oxide 10% Remainder carbon, accous material 49.5 cu. It./lb. 55.6 to 53.1 cu. ft./lb. Oxides of zinc, lead, iron and silicon DU P050314461 X-.Ua-. ' ; . .... -H. toa McCABE Sample A B C D E F G TABLE III Summary of Concentrations in Samples Collected (Grains per cubic foot at 60 F. and 14.7 psi) Time P.M. 2:51-5:02 5,2:51 - 4:21 4:26-5:02 5:46-9:30 5:46-6:46 7:09-8.09 8:30-9:30 Particulate Matter 1.421 1.962 -- 0.420 1.104 0.44.1 0.368 - Zinc Oxide -- 1.344 -- -- 0.482 0.153 0.103 Lead ____ 0.138 ____ -- 0.095 0.048 0.046 cide which type of equipment will meet his individual requirements. The Asso ciation's consultants estimate that the installation cost in collection equipment will range from $.25 up to $1.50 per cubic foot of gas handled, depending on the character of emission, the efficiency required, and the preference of the operator. The cost of the hood and duct systems is estimated to be from $.20 to $.50 or more per cubic foot of gas handled. The methods and procedures used by the ferrous industry for obtaining the data given in Table II is essentially the same as that previously described for the non-ferrous industry. The ratio of percent loss to total weight of the melt establishes that the effluent-melt ratio in cubic feet per pound is a measure of efficiency of foundry practice. On the basis of this ratio and from the study of the tabulations in Table II for the ferrous industry, it was found that the percent loss amounted to between 0.5 percent and 0.9 percent. One test showed a loss of 1.59 percent but a further study of the effluent-melt ratio shows that this high loss results from excessive dilution. During the major portion of the melt time, the ferrous industry violates the present law both as to stack loading and opacity. The total particulate matter, zinc oxide and lead concentrations for an open hearth furnace are shown in Table III. Particle size of emissions was deter mined from filtration Samples A and D, taken during the period between charges and the melting period follow ing the second charge, respectively. In addition, 14 separate samples were taken directly on electron microscope screens by means of a thermal precipi tator in order to obtain more accurate results on the smallest particle sizes. Particle size distribution is summarized as follows: St'ze Sample A 1-3 microns 10.5% 0.5-1 30.2% 0.15-0.5 " 49.0% Below 0.15 microns 10.3% 100.0% Sample D 4.1% 26.6% 49.9% 19.4% 100.0% Regulations relative to certain specific < dusts and particulate matter have been expressed in grains per cubic foot at 60 degree Fahrenheit and 14.7 psi pres sure. This approach encounters certain difficulties unless a standard quantity of excess air is established as well. It is anticipated 'that future regulations will 3 ? i J S DU P050314462 If. AIR POLLUTION 107 be on a mass-rate basis. In order to ob tain effective improvement in visibility and to bring about a reduction of sub micron material, it may be necessary to specifically limit it. BIBLIOGRAPHY ' Beer, Charles G. P. and Leopold, Luna B., "Meteorological Factors Influencing Air Pol lution in the Los Angeles Area." Trans., American Geophysical Union, Vol. 28, No. 2, (April 1947). 'Johnstone, H. F.. University of Illinois, Urbana, Illinois, Personal communication. Ch a ir ma n Bo w d it c h ; The leader of the discussion of Dr. McCabe's presen tation was formerly associated with Pro fessor Philip Drinker at Harvard, after which he was with Dr. Carey McCord in the Bureau of Industrial Hygiene at Detroit, and from 1941 to 1946 was director of that Bureau. He has been on the faculties of Wayne University and the University of Michigan and is now ventilation consultant to the Gen eral Motors Corporation in Detroit. Mr. William N. Witheridge. DISCUSSION Mr . Wil l ia m N. Wit h e r id g e [Gen It was stated yesterday by someone eral Motors Corp., Research Labora that much has been written on lead tories Division, Detroit, Mich.]: My poisoning and a great amount has been function here is going to be actually nonsense. So far as I am concerned, and literally as a leader because there there has been the greatest amount of are at least a dozen of you here whose nonsense published and spoken about work should be in the record in prefer the subject of atmospheric pollution, ence to mine. As a matter of fact, I and I do not refer to the specific case suspect, because of the lateness of the of Los Angeles. Every time a single hour, we may not give everyone a incident occurs, a great deal of excite chance to make the comments that they ment develops, way out of proportion t would like to make, because I am sure to the real nature of the problem. Al there are many who have rather strong though that no doubt hastens the inves feelings on certain phases of the subject. tigative process, against this must be It should be clear, I think, that the charged the community-wide injurious problem in Los Angeles is greatly dif effects of mass hysteria and, perhaps, ferent from that of accidental incidents widespread incidence of so-called "com such as occurred at Donora and those munity hypertension." which have appeared in the history of So far as my own opinions on some air pollution. of these matters are concerned, I think The problem of community pollution it would be well to delay them and to that is continuous and prolonged and get into the record some of the com develops a response such as has occurred ments of men who have specialized in in Los Angeles indicates definite need this field and who have done some very for a very good program of control interesting and important work in their and, of course, an excellent program own communities. of study of the scope of the problem I would like, first, to suggest that we and the possible methods of control. hear from Mr. Dyktor, who is now Com I think Dr. McCabe has, perhaps, the missioner of Air Pollution Control for supreme outdoor air pollution labora the City of Cleveland. It is quite a tory in the world. temptation for me to describe, briefly. IS giil m .< DUP050314463 108 DISCUSSION die nature of his program because I feel, in an administrative way, that it is a rather ideal combination, but I think Mr. Dyktor should do that himself, and I would like to hear from him now. Mr . H. G. Dy k t o r [Commissioner of Air Pollution Control, Cleveland, Ohio]: Mr. Chairman, I have certainly been taken by surprise. I settled myself down to listen to Mr. Witheridge review the paper given by Dr. McCabe. I did not expect to come here and expound my views on it. Some of you have heard them before, so I shall bore you again. In so far as Cleveland is concerned, we are quite conservative. We make haste very slowly, and I must admit that we do that under the compulsion of ignorance, because we realize that there is so much to find out in connection with the air pollution, and we have not yet scratched the surface. Therefore, it behooved us to move, as I said before, very slowly. The first step was to pacify the public that made the demand for the better life and expected miracles to happen overnight, just because legislation was. passed through council, and, on the other hand, to pacify industry which expected, as a result of this piece of legislation, that they would be dealt with harshly because they are, naturally, the source of emis sion of the pollution. So, the job is quite educational and informative, so far as I am concerned. The pacification of the public, at times, is quite possible, if you attend the socalled mass meetings where people use you as a target for their complaints and, if you have a thick skin, you can take it. You will find, however, that it generally develops afterwards that they did not mean to be harsh with you, that they understand what the problem is, and will go along with you. With industries, of course, I had an advantage. Because I had been in charge of industrial hygiene before I took on the job as Commissioner of Air Pollu tion Control, they knew me personally, they knew that I would cooperate with them and that I would not do anything drastic, in so far as they were concerned. Not knowing very much about air pollution control, because of the lack of fundamental information--and I admit that quite frankly--we have adopted the attitude in Cleveland that the various in dustries should be responsible for clean ing their own houses. We always went on the premise that they knew their own business far better than we did, and, if they needed help, they knew where to get it, and we were ready to furnish it to them. That was quite accepted, and, be lieve it or not, the industries in Cleve land, at least, under this process of cooperation and. education, have already spent hundreds of thousands of dollars in the matter of just fifteen months. As a matter of fact, we have their confi dence, and they are calling us in almost daily in order to help them out with their air pollution problems. I find that very fine because I am free to judge by results rather than by arbi trary limits. I would not know at pres ent what limits to set, even from the point of view of industrial toxicology, where we do have many, many yard sticks, of which some are good and some are not so good, as you know. When you get down to industrial nuisances, with their exceedingly low concentra tions, we really do not know because what may be a nuisance to one person may not be a nuisance to another. Hu mans vary that much, as you all know. Therefore, we are very cautious in es tablishing maximum allowable concen trations for nuisances. We have quite a variety of industries in Cleveland. We have three very large steel plants; we have dozens of found ries. We have the lead industries. We DUP050314464 Iijp AIR POLLUTION 109 have chemical industries, and others and, when I say "smoke abatement" I covering the entire gamut. I would be mean smoke that is the result of incom in a very poor situation if I produced plete combustion of fuels. Also we have, a set of maximum allowable concentra of course, what I consider, for the size tions for nuisances and made industries of Cleveland and for the activity, a live up to them, without knowing before pretty good laboratory. It took me quite hand that they could do so. a long time to sell the idea both to the We have not promised the people city council and to the budget director, elimination of air pollution, not at all. in order to get the necessary funds for We have only promised them that it it. would be reduced to a level where indus- Today we have excellent team work try and the community will be able to within the division, because we have live at least peacefully, if not quite com many staff meetings whereby I straight fortably, side by side. en out quite a few of these problems of I think, if we do that, we shall have personality, which you find among pro * accomplished a great deal, and, after- fessional people. I am also able to take * wards, it will be a job of keeping the sole responsibility for the conditions in pollution at that tolerable level. Cleveland, give service to the commun As far as our administration of this ity and to industry, and keep every problem is concerned, and of which Mr. thing under control, as far as I can. . Witheridge gave you an inkling, it came I do not mean to imply that we have about because of the fact that some of succeeded. We know that we have these activities were handled in different passed the apex of the curve. We are departments. Those of you who have on the downgrade but a little, but we had government experience know that are moving in the right direction. it is very" easy to pass the responsibility Thank you very much. from one to another, and thereby duck Mr . Wit h e r id g e : Thanks very much, the issue and let the other fellow carry Mr. Dyktor. the burden. But that did not produce I was very glad to hear, during Dr. results. McCabe's discussion, the mention of his Because of this lack of results there feeling that the standards for stack was a Citizens Air Purification Com "loading" or discharge into the atmos mittee appointed by the Mayor. I did phere probably in the future will be - not much care for the word "purifica based on the mass of material released tion" but that was none of my doing. rather than specific concentration. This committee prevailed upon the city Those of you who have copies of the fathers to do something about it. I was paper, perhaps may have received the consulted, and I suggested that these impression that concentration, as it is various activities be combined into one true in most of the ordinances around division, called the Division of Air Pol the country, is used independent of lution Control. At present we have in either the volume of gas discharged, or this division three bureaus: one, of the magnitude of the operation, or the course, the basic industrial hygiene number of stacks per unit of ground bureau; second, the industrial nui area, or any other rating devise you sances, which takes care of all the com might use. plaints arising from discharges into the The fact remains that a very, very free atmosphere from 'the various of small volume of discharge at several fending plants; third, smoke abatement, times the permissible limit may still be DUP050314465 no DISCUSSION a rather insignificant source of trouble in the community. Naturally, therefore, it is necessary, I think, in most of these problems, to make it clear early that possibly tremendous volumes of contam inated gas discharged at less than the standard concentration might be more troublesome than a, few minor sources that are obviously above the limits. I would like to have some comment from Dr. Fredrick at this stage, who is now director of the Bureau of Industrial Hygiene in Detroit, and in connection with the Detroit program of smoke abatement and pollution control, has provided the technical assistance to the Smoke Abatement Division in matters of air pollution investigation. Dr. Fred rick. Dn. Wil l ia m G. Fr e d r ic k [Bureau of Industrial Hygiene, Detroit Depart ment of Health, Detroit, Mich.]: The matter of basing limits on stack dis charge is the only satisfactory solution to the problem. The concentrations of contaminant out in the general atmos phere become so low that they practi cally defy our present analytical tech nics. It is possible to solve the problem, but the expenditure of time required is disproportionate to the facilities that are available for doing the job. I think most of us who had to suffer with the problem of measuring the amount of contaminant in the general atmosphere will be in agreement. If wc can base it on the source of contamina tion, the measurement problem becomes much simpler and, after all, that is the point where it is going to have to be controlled anyway. There is another comment I would like to make. In ail of the ordinances which have come to my attention, at mospheric contamination values and stack loading values are expressed in a queer and archaic system of units and nomenclature. The use of the metric system of nomenclature in atmospheric pollution work in general, particularly in the in dustrial hygiene and health field, is well established. We use the milligram per cubic meter nomenclature or the milli liters per unit volume nomenclature. The use of grains per cubic foot or ounces per cubic foot or pounds per cubic foot is a very awkward and in consistent system of nomenclature, and I believe that the ordinances should be revised. It will save the chemist from making recalculations, and it will cer tainly make it possible for people who are, in general, working in the field, to really understand the magnitude of the limit. The figures which I notice in the manuscript here this morning are quite incomprehensible to me, unless I get out a slide rule and apply a few factors. Ch a ir ma n Bo w d it c h : I would like to add to what Dr. Fredrick has just said with the comment that, while I was in Los Angeles and was talking with one of Dr. McCabe's chemists, I asked him what these regulations meant in terms of out more usual nomenclature in industrial hygiene. He replied that he hadn't the foggiest idea, but would be very glad to sit down with a slide rule and figure it all out for me. Dr . Mc Ca b e : We went through this argument. On one side we had the en gineers and on the other side we had the industrial hygienists and the chem ists. The engineers finally won out. The question of who is going to use the slide rule is, I think, what you have to decide. Mr . Wit h e r id g e : You need two col umns o data, so that nobody needs to use a slide rule. It is interesting to me to find on one program discussions both of indoor con tamination problems and outdoor con- DUP050314466 AIR POLLUTION 111 tamination. I think those of you in die industrial hygiene field have been, for some years, conscious at least of poten tial, and sometimes real strains that can develop between those who are trying to clean up the inside of plants and the other regulatory groups trying to clean up the neighborhoods .of plants, which is one of the reasons I stated earlier that Mr. Dyktor has the thing really under his thumb. Investigators who have worked pri marily on the inside of plants, neverthe less, as a result of the work they have done with rather specialized and elab orate devices, and trace-analytical pro cedures. have been called upon to study outdoor problems as well. The experi ence of most of those who have been in the field for years has been that, by force, whether they had an original in terest in the problem or not, they have had to develop one and comply with some of these demands, and that, in so doing, a great deal was learned about the simultaneous control of contamina tion, both inside and outside of the plant, which is really the best way of approach. 1 would suggest that we have a few comments at this stage by Dr. Sappington who has been a veteran industrial health consultant for many years and has expressed to me the fact that a good many of these outdoor pollution prob lems have been brought to him for study. Dr. Sappington. Dr . C. O. Sa p p in g t o n [Industrial Medical Consultant, Chicago, 111.]: Mr. Witheridge, I certainly want to make this short, because the hour is quite late. My experience in this field is almost entirely limited to the medicolegal as pects of it, which are highly contro versial. However, I see, both as a phy sician and an industrial hygienist, that there are certain parallels in industrial hygiene codes and in the regulations for atmospheric pollution. _ I think it might be well, and I do make the suggestion seriously, that those who are devising regulations or codes, as you may call them, for preventing atmosphere pollution, or controlling it, might very well share their experiences with those who have been working on industrial hygiene codes. I would like to make just two refer ences here. These may be old to most of you but I found them very helpful. Con cerning the remark that a great deal of "hokum" has been written on this sub ject, as well as on lead, I would like to cite two references which I believe will be quite helpful. One is "Atmospheric Pollution by Heavy Industry" by E. Wendell Hewson of Toronto, published in Industrial and Engineering Chem istry, March, 1944, in which he tells about the conditions at Trail, British Columbia. The other one is also en titled "Atmosphere Pollution" by our friends Hemeon and Hatch, also in Industrial and Engineering Chemistry, May, 1947. I feel that there are certain very basic things in these two references which those of you who don't know about might consider. Mr . Wit h e r id g e : Thank you verymuch, Dr. Sappington. In justice to the following speaker, I believe that all further comments on this subject should be deferred until after the luncheon, because we have a period for discussion this afternoon and this subject can then perhaps be the target of further comment. Ch a ir ma n Bo w d it c h : Our final paper on the morning program will be by the Assistant Professor of Medicine, Uni versity of Colorado Medical Center, where he was largely responsible for one of the few scientific appraisals of aluminum therapy that has thus far been made. Dr. John W. Berry. iT i DUP050314467 ALUMINUM AND SILICOSIS By JOHN W. BERRY, M.D. Assistant Projessor of Medicine, University of Colorado Medical Center, Denver, Colo. Since Denny, Robson and Irwin pub lished their historic papers in 1937 and 1939, those interested in silicosis have been anxiously anticipating information derived from study on the human which would allow them to fit these experi mental observations into their proper place in the management of the silicosis problem in industry and in clinical medicine. Since the first of these papers appeared over eleven years ago, it would seem that considerable useful informa tion should now be available; such is largely not the case. The answers to certain very important questions must be known before it will be possible to determine what part, if any, aluminum inhalations are to play in the treatment and prevention of sili cosis. We must know the effect of aluminum on man, the effectiveness of aluminum in the prevention of silicosis, the effect of aluminum in patients dis abled by silicosis, and the effect of aluminum in doses that are used prophylactically and therapeutically on tuberculosis. Partial answers to these questions are available. The fact that aluminum is very prob ably harmless to the human lung can be inferred from the following informa tion. You are all probably familiar with the frequently cited observations made at the Aluminum Co. of America in which the study, both clinical and of the chest x-ray films, of 125 men who had been exposed to very great concentra tions of aluminum dust for many years, failed to disclose any pathologic change which could be attributed to the alumi num. The British Medical Council, after reviewing the findings of 50 workers exposed to aluminum in high concentra tion over a long period of time, were able to report in 1936 that there was no evidence of pathological change due to the inhalation of aluminum dust. Hunter, Milton, Perry, and Thompson studied persons who were engaged in the grind ing of aluminum propellors during the war, and again there is no evidence that aluminum was in any way toxic. For the past several years in English pot teries, aluminum has been substituted for quartz in the manufacture of dishes. In this operation a large number of men have inhaled considerable aluminum over a period of years, and again there is no evidence that aluminum is patho genic. Finally, in the United States, Canada and other countries, many thou sands of men have inhaled aluminum dust as a prophylactic and therapeutic agent in silicosis, and in these cases there is no convincing evidence that aluminum has caused any pulmonary change. On the other hand there have been several reports from Germany in which a peculiar pulmonary disease has oc curred in persons exposed to large quan tities of aluminum. While aluminum has been thought to he the agent respon sible for this condition in Germany, there is no proof of this. Follow-up studies on these cases and on this prob lem are now being carried on by English investigators; the final answer is not available. Recently Riddell and Shaver have reported a peculiar pulmonary disease occurring in men who have been exposed to large quantities of aluminum. These cases closely resemble those which have occurred in Germany. Again, in none of these cases has aluminum been proved to be the etiologic agent; in fact there is considerable doubt that alumi num is responsible for these cases, but 112 DUP050314468 ALUMINUM AND SILICOSIS 113 f it is well to keep these reports in mind. will be granted is that proper dust In spite of this it is probably safe to control be instituted in plants in which assume that aluminum, as it is used pro- there is a silicon hazard. It is only after ff` phylactically and therapeutically, is safe. the dust in the plants has been con 7 At least there is no convincing evidence trolled to the satisfaction of the McIn available to show that aluminum has tyre people that aluminum inhalations in any case been harmful. are allowed. If dust is suppressed prop In regard to the prevention of silicosis erly, there will be no silicosis, and there by the use of aluminum, I think that fore one cannot use such groups to judge it has been established beyond a reason- the effect of aluminum if in reality there able doubt that aluminum in the proper is no silicon hazard. However, in many S compounds and in adequate dose will situations adequate dust control is very prevent the development of silicosis in difficult; for this reason there may be experimental animals. This has been some justification for the use of alumi well demonstrated by Denny, Robson num in the plants. But, when it comes and Irwin and amply confirmed by to using statistics derived in this way to Gardner and his group at the Saranac prove the value of aluminum, one cannot Laboratory. There are two reports in tell which of the two factors is respon the literature which tend to cast some sible for a reduced incidence of silicosis, doubt upon 'this conclusion, but I think the dust control or aluminum. For this the failure recorded by these men was reason it is impossible to use the inci due to experimental difficulties, rather dence of silicosis before the institution than to failure of aluminum. of aluminum and that afterward to form Shortly after the discovery that alumi an opinion as to the effect of aluminum. num would prevent silicosis in animals, In order that I am not misunderstood, I several projects were started to test its am not suggesting that dust control be effectiveness in the human, both in the neglected and aluminum substituted, but prevention and for the treatment of I only wish to point out that in this silicosis. But in spite of the fact that situation the effect of aluminum will re -j, several thousand men have received main unknown. In view of these facts, prophylactic aluminum inhalations, it is it has been suggested that since some impossible at this time to arrive at any men will refuse aluminum inhalations conclusion. There are several reasons and they will work in the same environ for this. First of all, silicosis is a disease ment with those taking the aluminum, which develops very slowly and there that the incidence of silicosis in these has been insufficient time in most in two groups be compared in order to stances to evaluate its prophylactic value. form an opinion as to the effect of alum But aside from the time factor, I have inum. This plan has many possibilities considerable doubt as to whether we are of error and is very comparable to the going to be able to evaluate the prophy control system used in the early work lactic value by the use of the results with BCG, and I am sure that you are of the work now under way or already familiar with the doubt and indecision reported. The entire procedure, as you surrounding BCG. Men who refuse to undoubtedly know, is patented by the take the aluminum can reasonably be McIntyre Research Ltd., and in order to expected to be the same men who would use aluminum, a license from the McIn deliberately violate any measure for dust tyre Research Ltd. must he secured. One control which depended upon workman of the conditions upon which a license execution, and for this reason this is a (ft mam DUP050314469 114 KERRY group in which silicosis is most likely to occur. Therefore, in my opinion the use of this sort of control will of neces sity weigh any statistics very heavily in favor of aluminum. It seems to me that in order to arrive at the answer to this problem, it will be necessary to do scien tifically controlled. experimentation by means of large numbers of men over a long period of time, during which time the magnitude of the silicon hazard is known. These men must be divided into two groups, not haphazardly, such as using those who refuse inhalations, but by some deliberate plan so that by chance we would have comparable groups. It is only by use of this or some other similar plan designed to be as nearly foolproof as it can be made, that we will arrive at a reasonable con clusion in regard to the value of alum inum in the prevention of silicosis. Most of the work reported to date is actually of no scientific value, except perhaps to demonstrate the safety of aluminum in halation. I realize that there is little reason to think that aluminum will not be as effective in man as it is in the ex perimental animal, but until it is proved to be as effective in man, we cannot accept it without reservation. The evaluation of the therapeutic ef fect of aluminum in silicosis is as diffi cult as or more difficult than is the evaluation of the prophylactic use. In the reports available, there are many cases described as disabled by silicosis without a clear definition of what is meant by disability. It should be noted, however, that many of the persons said to be disabled were able to work, and I think these cases more properly should have been called symptomatic cases of silicosis, or described as partially dis abled with a note as to exactly what is meant by partial disability. In the main, the improvement reported in the litera ture is subjective improvement. In other words, the patient, thinks that he feels better. I think it is fair to compare such evaluations to the testimonials we fre quently read in newspapers which are used to prove the' value of many nos trums. The silicotic has a disease which has frequently caused the deaths of many of his friends and associates and for which there was no hope of treat ment until aluminum was introduced. If we remember this, it is easy to under stand how the administration of an agent thought to help silicotics will brighten the outlook of these individu als. For these reasons we must turn to the reports in which there has been some attempt to determine the effect of aluminum by objective methods. The early report of Blaisdell, Crombie and MacPherson described the pulmo nary function tests used by them. The tests used by them were apparently as good as are available at the present time. By means of these tests they showed that five of their treated men showed definite improvement in pulmo nary function. However, one member of their so-called control group also showed significant improvement in pul monary function. In view of the fact that the treated group was much larger than the untreated group, the percentage of those treated showing improvement was 14.7 and of the untreated group, one patient amounted to 12 percent of the untreated group. They do not give the specific results of their tests, and in view of the fact that one man who had received no aluminum and had not even been subjected to the same suggestive management as the treated group, showed improvement, I think we must be very skeptical of this reported result, especially since the percentage of im provement is almost the same in both groups. Hannon, in a recent report, claims 80 percent of the treated patients showed at least 20 percent improvement DUP050314470 ALUMINUM AND SILICOSIS 115 in their "respiratory effort." He does not say specifically which tests of pulmonary function were used, but I presume it was the maximum breathing capacity. He did not test those who did not claim im provement; at least he makes no report of such tests. Wright at the Saranac Laboratory has done physiological stu dies on pulmonary function in men treated for silicosis, but he can demon strate significant improvement in only 5 percent. In addition to silicotics, Wright has taken another group of men who, although they were not silicotic, thought they had the disease. He treated these men with aluminum and could demonstrate considerable subjective clin ical improvement in them. At the University of Colorado we were skeptical of the value of aluminum in the relief of disability when it was due to silicosis. We undertook a study which I will briefly summarize, although I have little to add to the published re port. We selected a group of 42 sili cotics because they were disabled to varying degrees by their silicosis, be cause they had no compensation claims which would tend to color their symp toms, and because they were free of demonstrable tuberculosis. At the onset of this work we did not use a control system because we thought that by con ducting the experiment for a sufficient period of time we would be able to de termine the real value of aluminum, but as the work progressed it became obvi ous that we would never arrive at any answer without a control group, since those receiving aluminum were so en thusiastic and believed themselves to be so much improved, in spite of obvious deterioration of health of some cases. For this reason we altered the apparatus by which the dust was administered so that we could allow certain men to go through the same routine but receive only air from the machine. These men who were selected as,controls did not know, of course, that they were not re ceiving aluminum. Soon after the initia tion of the control system we felt that our skepticism was justified, since im provement very comparable to that ob served in the men who had received aluminum became evident in members of the control group who had received no aluminum. In the early part of our work, after a few inhalations of alum inum, men who were unable to walk up stairs previously, were able to do so. This was very impressive, but after we initiated the control system, we noted the very same improvement in the men who had received only air. To be cer tain there was no accidental contamina tion of the air by aluminum, we checked the control outlets and found no signifi cant amount of aluminum in the air breathed by the controls. We used only the amorphus hydrated alumina XH 1010 as recommended by Gardner. The men received on the average a total of 130 treatments, spread over a period of one year. The men breathed an atmos phere containing 300,000,000 particles of alumina per cubic foot. The particle size averaged 1 to 3 microns in diame ter. How much of this dust reached the alveoli is unknown. Since the conclusion of this work in January, 1948, I have had the oppor tunity to examine a few of these men. Members of both the control and the treated groups continue to state that they have been definitely helped by this treatment. This is true even when it is obvious that the man's health has de teriorated, The most interesting of these cases is one to whom I talked two weeks before his death, at which time he was very firm in his conviction that he had been improved. At the time of this ex amination he was extremely dyspneic, had a large liver, very marked ankle edema, and it was obvious that he was J I DUP050314471 110 BERRY seriously ill. Following death I was un able to secure postmortem examination, but it seems to me reasonable to suppose that he died of pulmonary insufficiency which precipitated the right heart fail ure, Several other men who received aluminum at the University of Colorado have died, but 1 have been unable to secure postmortem examination, since their home is usually at some distance from the school and I have not learned of their death until after their funeral. Most of those interested in aluminum therapy have recommended that the in halations should not he given to persons who have obvious evidence of tubercu losis or in whom there is found reason to strongly suspect the presence of tuber culosis. The reason for this is based mostly upon the work of Gardner and his group, in which they demonstrated that the administration of large amounts of aluminum to animals decreased the resistance of those animals to tubercu losis. The doses used in these experi ments were far larger than any used in the prophylactic or therapeutic adminis tration of aluminum. The only reference in the literature which I can find which suggests that the inhalation of aluminum in the hu man leads to premature development of tuberculosis is contained in the report of King and Sutherland to the British Research Council in which Dr. William Taylor of the Workmen's Compensation Board of Timmins, Ontario, states that he believes two cases have developed tu berculosis possibly as the result of alum inum inhalations. King and Sutherland were not convinced that these cases of silico-tuberculosis were in any way un usual, and there was no proof that they were due to aluminum inhalation. On the other hand, in the report of W. E. George on a visit to the United States, he quotes Dr. Crombie as saying he had treated persons with silico-tuberculosis without detectable harmful effects. Dr. Hannon has told me that he has treated a few cases of silico-tuberculosis with reduced doses of aluminum without any demonstrable harmful effects. These cases certainly form an inadequate basis upon which to rest an opinion as to the effect of aluminum inhalations. It may be interesting to note in this connection that in a report by Dr. George of Austra lia, he cites some work by Gardner in which animals with silico-tuberculosis were given aluminum which seemed to prolong their life without actually influ encing the course of the tuberculosis. It is generally accepted that silicotics frequently become tuberculous. This view has been challenged by Ornstein and a few others, but the vast majority of those who have seen large numbers of silicotics are convinced beyond any reasonable doubt that tuberculosis com plicated a high percentage of cases. The reason for the unusual frequency of tu berculosis in these patients is unknown. We do know that the presence of silicon in culture media will cause the tubercle bacilli to grow faster and more luxuri antly. It is also known that the presence of silicosis in animals will cause such animals to exhibit less resistance than normal to the tubercle bacillus. Although the solubility theory of the pathogenesis of silicosis is not univer sally accepted, it would seem to me to be the most reasonable assumption to explain the pathogenicity of silicon di oxide available at the present time. It would also seem to me, in view of the fact that tuberculosis complicates sili cosis in any stage, that the decreased re sistance to tuberculosis must be in some way connected with the soluble product-, of silicon dioxide. If this be the case, and if aluminum is capable of decreasing the solubility of silicon, then perhaps the use of aluminum, while of little value in re lieving the symptoms due to silicosis, DUP0503144-72 ALUMINUM AND SILICOSIS 117 I may possibly prevent die development of tuberculosis in silicotics. I realize that the weight of evidence as it is known at the present time is heavily against the probability of this idea and I make this suggestion somewhat in desperation be cause of the disastrous effect of tubercu losis when it occurs in the presence of silicosis. I am aware of the fact that in a few cases tuberculosis has become first evident either during or following alum inum inhalations. But I am of the opin ion that if there is the slightest chance of reducing the incidence of tuberculosis by the use of aluminum, we should take that chance, since we have nothing else to offer these men. In our very small group at the University of Colorado, there was no instance of tuberculosis in the treated group either during or fol lowing treatment. This applies only to those whom I have had an opportunity to examine, approximately half the group. During the same interval a smaller group of controls who received no aluminum showed two cases in which the onset of tuberculosis occurred many weeks after the beginning of the experi ment. In summary I should like to say that because the results in animals are so striking, the value of aluminum in the prevention of silicosis in the human should .be determined, but in my opinion the methods used at present probably will not produce the answer. If alum inum proves to be helpful in die preven tion of silicosis, even then it should not be used in preference to dust control. This may prove to be a real danger be cause of the expense of an adequate dust control program. It has been sug gested that aluminum be used in two distinct situations: first, in those indi viduals who develop silicosis in an en vironment which is safe for most workers, or develop silicosis after an abnormally short period of exposure; and secondly, where the industrial situa tion is such that dust cannot be con trolled for short periods of time. In regard to the first group, I am sure that there are those who develop silicosis more rapidly than the average for an unknown reason, but in my opinion the majority of such people fall into one of two groups: those who are mouthbreathers or because of nasal pathology their nasal mucosa is not as effective as normal in protecting the respiratory tract, and those who must take in to their chest an abnormally large amount of air to secure a given amount of oxy gen. Into this group fall such diseases as chronic asthma, chronic bronchitis, and other pulmonary diseases. Men with these ailments should he excluded from employment in dusty industries. Be cause this would reduce the number of men who developed silicosis in an en vironment which is safe for most work ers. In the second group, it is true that there are instances where it is not pos sible to constantly control the dust, but these of course should be held at a min imum before aluminum is used. I think there is very great doubt that aluminum inhalations are actually capa ble of relieving the symptoms of sili cosis, but there may be a remote possi bility that by the use of aluminum the incidence of tuberculosis in silicotics can be reduced. There is no experimen tal basis for this opinion. Early in the course of this work it was hoped that aluminum would stop the progress of silicosis, if it did nothing more, but there is some evidence that it does not halt the disease. In the report of King and Sutherland previously quoted they mentioned the fact that Drs. Riddell, Cunningham and Taylor have noted that in the cases reported by Crombie, Blaisdell and MacPherson 23 out of 46 treated cases have progressed. This progression was evident in some DUP050314473 118 DISCUSSION who had claimed they were Letter, Rid dell mentions that other cases had pro gressed in spite of aluminum adminis tration. Therefore we are forced to conclude that aluminum, in some cases at least, does not halt the progress of silicosis once the disease is established. Ch a ir ma n Bo w d it c h : The discussion of Dr. Berry's paper will be led by one of our leading authorities on silicosis, especially in the foundry industry. He has probably the most extensive collec tion of roentgenograms of this disease in the United States, has written very extensively on the subject, and is con sultant to many industries throughout the country. Dr. 0. A. Sander of Mil waukee. DISCUSSION Dr . 0. A. Sa n d e r [Milwaukee, Wis.] : All who are interested in this matter owe a debt of gratitude to Dr. Berry and his co-workers in Denver for this clear-cut and well controlled investigation. Ac tually it was the first and still is the only scientifically controlled study of tlic ef fect of aluminum in human silicotics. It Is the only human experimentation from which any valid conclusions can be drawn. What we long suspected was proven beyond doubt; i.e., that it was not the aluminum which was responsible for the subjective improvement claimed by some 65 percent of silicotics so treated. Sugar pills would have accom plished the same results had they been publicized as the long-sought-for cure. This evidence should not halt all fur ther investigations, however, into the possible therapeutic value of aluminum. There still is the group of cases, small in number but tremendously important, in which silicosis develops rather rapid ly. Where one finds a sandblaster, for example, as I did recently, who last year had only increased trunk and linear markings on his chest film and this year has a well developed nodulation because he had had a defective helmet which was not properly maintained, any therapeu tic measure which offers even the most minute ray of hope of arresting the almost certain progression of his sili cosis should be attempted. There is evidence now, as stated by Dr. Berry in quoting Drs. Riddell and Cunning ham, that metallic aluminum is not halt ing such progression very effectively. The hydrated alumina and colloidal alumi num hydroxide, however, may be more effective with such cases. This statement is based on animal work at the Saranac Laboratory from material as yet unpub lished. In a recent communication from Dr. Vorwald, he stated that there was marked arrest of the silicotic changes which precede the formation of fibrous nodules when such animals were exposed to hydrated alumina. Comparable pro tection was not observed when similar prenodular silicotic animals were exposed to the metallic aluminum. Unfortunate; ly, for the purposes of experimental evaluation at least, such rapidly develop ing silicosis is very rare today. Present evidence, however, suggests that the hy drated alumina should be started at once on such cases when discovered, provided a tuberculous background for the rapid progression can be ruled out. As for the general prophylactic use of aluminum in foundry workers, I should like to say a few words about that. As a result of the aluminum publicity sev eral years ago, there were demands from many foundry employees in our area for an aluminum dusting program. I have consistently discouraged them for sev eral reasons. First and foremost, found ry silicosis can be prevented and is being prevented today by adequate dust con- DUP050314474 119 trol. We see only very occasional cases of new silicosis developed since the con trol programs have been enforced, such as occasional sandblasters whose pro tective equipment has failed. Such cases can be treated individually. I visualize more harm than good by an over-all dusting program because laxity in dust control is bound to creep in no matter how rigid the rules. The other reason I have discouraged aluminum dusting for foundries is that the atmospheric dust in foundries is always mixed and already contains com ponents which have been shown experi mentally to be almost as protective as aluminum. In foundries today, the silica content seldom exceeds 20 to 25 percent, with 35 percent as the upper limit in the poorest controlled foundries. That means that 65 to 80 percent of the dust which foundry workers breathe tends to prevent or at least modify the reaction of the silica they are breathing. These other components are primarily iron and carbon. It hardly seems necessary to add another component to such mixed dusts. The only exception, as already stated, is the occasional sandblaster who through equipment failure develops a rather acute silicosis. His exposure to free silica has been too excessive for the mixed dust in the general foundry to be at all protective. In closing, I agree in every respect with Dr. Lanza's statements in his ex cellent editorial in the American Review of Tuberculosis of June, 1948 and I recommend that all who are interested in this matter read it. In the same issue, by the way, is Dr. Berry's first paper on his work, which also is fascinating reading. I quote from Dr. Lanza's edi torial: "It is to be hoped that further con trolled studies will be forthcoming, and that the'propagation of the alumi num treatment will be stayed until further information as to its effects is available. It is especially desirable that the possible beneficial effects on early stages of silicosis be thoroughly explored. The continuation of present practices will tend only to cause fur ther confusion and, in the long run, may defeat the purposes which the Canadian group originally had in mind." Ch a ir ma n Bo w d it c h : We seem to have about 15 minutes to go. Who would like to add a contribution to the dis cussion of this subject? Dr . Da v id R. Jo h n s [Consultant, American Smelting & Refining Co., Eagle-Picher Co., and Glidden Co., East Chicago, Ind.]: Mr. Chairman, all I would care to say at this time is that we have been trying out aluminum therapy at two plants, but on a large scale in one. Our five-year period will shortly be up. I am concerned about a man who has secondary or third stage silicosis and who is terribly disabled, but I do not believe that you can change scar tissue or fibrosis. My concern is with the possibility of slowing up these men who have reached a 2+ or a potential pri mary silicosis, and we are now complet ing a five-year period. Wc see nothing in our observations at the present time to discontinue the use of aluminum. We are going on with it, and we expect to publish what we feel we have seen in that five-year period. I might say that we are treating about 1,200 cases at the present time, Ch a ir ma n Bo w d it c h : Are there fur ther comments on this subject? If not, we will continue after lunch. . DUP050314475 TUESDAY LUNCHEON SESSION NOVEMBER 16, 1948 Ch a ir ma n Bo w d it c h : When I was arranging the program lor this confer ence, I got to thinking about the Saranac Silicosis Symposiums of the 1930s and the summations that my old and good friend Roy Gardner made at the close of those Symposiums, and I found my self wondering who could do the same for us at this conference. Rather na turally, I thought of another equally old and good friend, not only of Dr. Gard ner's but of mine. I asked him to perform this service for us and charac teristically, he consented. To anyone who knows anything about industrial hygiene, he needs no introduc tion whatsoever, so I name him to you, as he was affectionately designated at the time that he received the Knudsen Award for outstanding service to indus trial medicine, Tony Lanza. SUMMATION OF CONFERENCE PROCEEDINGS Dr . An t h o n y J. La n z a [Associate Medical Director, Metropolitan Life In surance Co., New York, N. Y, ]: Mr. Chairman, ladies and gentlemen: In the course of an active and sometimes dis oriented career, I have attended all kinds of meetings. I feel this is one of the best meetings which I have ever attended. 1 think it is good because I learned something, and, strangely enough, I think that is why most of us come to meetings of this sort. I have learned a lot in the last two days, and it is valuable knowledge. One thing that this session has emphasized wisely is that, in this whole matter of industrial health, you are dealing with two skills -- medicine and engineering. I do not think that either one is more important than the other. But, on the other hand, I will say this. The doctor by himself can do a pretty good job, the engineer by himself can do a pretty good job, but only by working together and appreciating each others' responsi bilities and points of view can they do the sort of rounded-ouL job that the 120 exigencies of industry [when I say "in dustry" I use the word as an all-inclusive term, embracing both the employer and the workers] demand. I want to touch briefly now on some of the high spots of this meeting, as they seem to me. Dr. Harrold put his finger on some thing, when he spoke about particle size. I have been in this business quite a long time, and for a number of years we used to talk, and we still do talk, rather glibly about particle concentrations in the atmosphere, and so many million particles per cubic foot, or so many milligrams per cubic meter, and we thought that we knew everything there was to know about particle size. I made this kind of a statement over and over again [there is nothing like eating your words once in a while, you know]: that it took very small particles, to get into the lungs, that most of those that did damage were probably below 5 microns in size. That is all right: I go along with that yet. Also, when you got down below half a micron, or some- DUP050314476 si'h SUMMATION 121 * ' " ' j:-''5'- where around that, these sizes did not have much significance; that they floated in and out with the tidal air and were not of much concern. I think probably that statement is as erroneous as any thing can be. In these questions of dust pollution, whether you are talking about substances that act like silica, asbestos or diatomaceous earth, or suhRtanc.es that act like lead, maybe the electron microscope is going to change a lot of our thinking. I am beginning to think now that particle size is one of the things about which we know extremely little, and yet which may be-the determining factor in some of these questions that puzzle us; why we get contrary evi dence on clinical examinations or on laboratory examinations of people who we think are exposed to the same type of hazard. Dr. May R. Mayers, with that charac teristic good sense that always distin guishes her, uttered a truism that we should always remember, and that is that we must consider the patient as a whole. Somebody said, in talking about that at our meeting, that the laboratory find ings often do not indicate the serious ness of the condition. You hear a lot about industrial medi cine and industrial hygiene nowadays, and that it is a branch of public health or that it is a branch of preventive medi cine, and so on. These statements are partially true, but, after all, the physi cian and the engineer, and particularly the physician who gives his time to in dustry is dealing with people just as much as the general practitioner up the block who takes care of little Susie or Johnny or the boss or his wife. They are dealing with people. That is why, as one of your commentators said yester day, the patient-physician relationship is so important. I think it was Dr. Belknap who said that. Then our old friend Dr. Johns made a statement, the importance of which I do not know whether you all appreciated when he said it. What did he say? He said, "1 visit my plants. I visit my plants every week." Yon know, I get a lot of diagnoses, made by presumably good men who are supposed to know their business. They make these diagnoses by adding up two and two and getting fourteen. They would not make these diagnoses if they were familiar with the conditions under which their patients worked; they could not make them. But, as Dr. Johns said, he visits his plants, and that is why he is a successful industrial physician today. I am no expert on lead poisoning. I have seen very little of it. But it seemed to me, in listening to the discussions yesterday, that there was a general agreement on the treatment, and I could not hear that there was any very active opposition to the statement by Dr. Wilentz that deleading is dangerous; he did not believe in deleading. As far as I know, that statement went unchal lenged by the persons here. I think one did say that it was of doubtful value, but apparently the general opinion was that it was not good practice. There was general agreement that there is much mild lead poisoning, that there is not much aggravated or severe lead poisoning, and that most of the ill effects of lead are found in the small plants and among the occasional users. I think that is absolutely true. Our own experience seems to bear that out. Yet every once in a while, you know, it crops up in a way that takes you competely by surprise. Some time ago I had occasion to visit a plant where the amount of pre sumably nonoccupational illness was ex tremely high, and most of it fell into the general classification of gastro-in- J DUP050314477 122 LANZA testinal diseases. I thought that looked funny because, as you gentlemen know, the general American ratio of sickness among the population is three cases of respiratory to one gastro-intestinal. That seems to be about the American average. In this particular plant it was the other way around^, three times as many gastro-intestinal cases as there were res piratory. I went down to see this plant. It was a perfectly beautiful plant. It was fairly new, beautifully laid out, designed, ven tilated and illuminated. Everything was top notch, but one item was wrong. One of the prime operations consisted of the assembly of small parts, which was done by girls working on each side of a long table with a moving belt down the middle. They assembled the parts, and then they were moved up to the end of the table, and at the end of the table was a man who had a lead pot, and he soldered them. Here was the wall with the windows, and the windows were all open. It is perfectly obvious what happened. The fresh air, the sunshine and every thing was lovely, but the fresh air blew all the fumes from the lead pot right on down the table; they leaded everybody in the place, from cellar to garret. They did not miss anybody but the superin tendent, and I was not sure about him. None of them had wrist drop or colic, or anything like that, but did lose their appendixes and a few of them lost their gallbladders, too. So, you never know. Dr. Gray touched on something that I think is giving all of us a great deal of trouble and a considerable amount of worry, and I am quite sure that I have not got the answer. But Dr. Gray, in the course of his comments, said that the physician on call does not have the time nor is he paid to inspect his plant. Golly, how true that is! And how much trouble and how much mistaken diagnosis and how much poor practice is covered in that sentence! This morning I listened more or less entranced by the discussion of Dr. Eagle and Dr. Corwin, well considered, judi cious expressions of opinion, founded on research principles and sound re search procedure, talking about BAL. I thought it a very careful and very scholarly presentation. As I listened to their discourse and looked at those fascinating cartoons of Dr. Corwin's, the thought occurred to me that maybe two years from now, if we were looking over the bound pro ceedings of this meeting here today, probably we would think then that that joint presentation was the high spot of this meeting. The subjects of the coordination of medical services and of the role of the state agency with respect to the control of working conditions, I think were very amply and very ably covered by persons who had had a great deal of practical experience in those fields. The state has an interest; the com munity has an interest. I sometimes think that the poor working conditions and certain amount of turmoil that are seen at times, where the industry is off the beaten path, are due to that fact, that it is away from our common knowl edge. Then this morning we heard Dr. McCabe from Los Angeles. I was out on the West Coast for four months last year, and I spent some time down in Los Angeles. I was interested in the synthetic rubber plants that have been erected south of the city. That was right after one of the outbursts of smog and popular indignation and the mild de gree of hysteria that goes with that sort of event. You know, nothing makes peo ple so unhappy and gets them so excited as something that smells bad. If you DUP050314478 A m fetfc- have ever noticed it in your working conditions, they will eat silica dust, they will eat lead, they will deal with any thing, but let something smell bad, and, brother, they are right up in arms! It is peculiar, but it is the truth. I was fascinated by Dr. McCabe's description of the interplay of meteoro logical conditions and the exhausts from the stacks of different types of industries. He made it very clear as to why what happens, does happen. The remedy, of course, is not so simple. But, on the other hand, in talking to students in recent years, I have com monly made this observation: the Ameri can people have been educated to spend enormous quantities of money on pro viding their communities with good drinking water. You can take an auto mobile trip from Maine to California, or from Florida to Seattle, and you will stop at all kinds of places, big city hotels, tourist camps, tourist boarding houses, roadside diners and whatnots, and vou can feel almost certain, when they put a glass of water in front of you, it is fit to drink. To be sure, it may taste a little of chlorine, but one cannot be too finicky about that. The reason that is so is because the American public has been educated to demand good drinking water. They have not been educated to demand good air. They are just beginning to wake up to the fact that maybe they can do something about atmospheric conditions, and that it is not necessary to have their community, including the places where their homes are, blanketed a good many days a year with a lot of fog and smoke. The people who run the department stores have been screaming about it for years, because the economic loss to them is terrific. We talked to some of the de partment store people in Pittsburgh, and you would be quite surprised to learn the extent of the loss to them due to atmospheric pollution and the dirtying of their silks and rayons and linens and whatnot, all of which, of course, is passed on to the consumer. You under stand that. But we believe that the next great forward step in public health in this country is going to be in connec tion with the control of atmospheric pollution. Far be it from me to comment on the interesting remarks of Mr. Witheridge, Mr. Dyktor and Dr. Fredrick, because they were in realms in which I have no experience, but it seemed to me that the indications are clear that everybody is beginning to get disturbed, and the sort of thing that happened in that little town in Pennsylvania the other day, regard less of how correct the newspaper ac counts may be, is going to stir things up quite a lot. Well, that brings us to the last paper on the agenda this morning, the one on aluminum therapy. It must be twelve years since Dr. Roy Gardner, Dr. R. R. Sayers and I first went to Timmins, On tario, to see their demonstration of this aluminum. We spent a day at the Banting Insti tute. Dr. Banting was alive then, of course. I was very much impressed -- we were all impressed -- with the people who constitute McIntyre Research, Ltd. I think they are an awfully good bunch of fellows. I think they are absolutely on the square. Well, I think the whole aluminum question is beginning to lose some of its point, but I will say this, that Dr. Berry presented a well-balanced, well-eonsidered, fair paper. I thought it was an honest and fair statement, and he and his associates are in a position to make a well-balanced statement, because they have done a well-balanced job. Hind sight is always better than foresight. I think there have been a lot of mis takes made in the whole way this alum- mmm DUP050314479 124 LANZA inum business was handled. I am not critical of it, particularly. I simply feel that conditions in industry are such that you cannot run a scientific experiment or a control where your people are go ing and coming, and they are here today and gone tomorrow, and you never see them again. How,can you follow them up? How can you know what happens to them? You don't. It might be pos sible if you were dealing with an acute condition, but not a chronic condition that may take fifteen or twenty years to develop. I am only going to say one thing more about this. The last time I was in To ronto", and I went up there at the invita tion of the McIntyre people, I made this observation to them. I said [and, mind you, I do not ques tion their motives in the least], "You have been running this thing now for going onto eleven years. You must have learned something. I think that, inas much as you are spreading it and have set up machinery to introduce it around industry -- in other words, out pushing it -- I do think that you ought to tell us what the Canadian experience is. Let me put it very simply: What has become of the people to whom you started giv ing aluminum ten years ago? Are they alive? Are they dead? What did they die of, if they did die? What is their physical condition at the present time?" This afternoon 1 understand there is going to be a general discussion, with no holds barred, and it seemed to me I saw some of the gentlemen out in the hallway sort of sharpening up their razors. So, I hope you have a grand meeting this afternoon. I think the Lead Industries Associa tion has done itself proud, and I think Mr. Manfred Bowditch has done a very good job. Ch a ir ma n Bo w d it c h : We will re sume in the other room in five or ten minutes. DU P050314480 I! -v. TUESDAY AFTERNOON SESSION NOVEMBER 16, 1948 Ch a ir ma n Bo w d x t c h : I think we might as well get started on our round table. I can assume that the first subject we should go back to is the stippled cell - urine discussion of yesterday, which did not seem to have been ex hausted by the time we had to leave it for other matters. Is there anyone who would like to continue the discussion on this subject? ROUND TABLE DISCUSSION Dr . Al b e r t S. Gr a y [Director, Bu between the porphyrin content and the reau of Industrial Hygiene, Connecticut basophilic aggregation and the lead in Department of Health, Hartford, Conn.]: urine. I just want to ask a question. We were I believe, as these gentlemen said, the using stipple cell counts some years ago, thing to do is to see the process, of and then Carey McCord and the U. S. course, and to see the individual. Public Health Service persuaded us to Dr . Wil l ia m G. Wo o d [National use the basophilic aggregation test. We Lead Co., St. Louis, Mo.]: Concerning are doing that, and it seems satisfactory, the basophilic aggregation, from our and I am not going back to the stipple observation over many years at the St. cell counting unless a good reason is Louis Lead and Oil Works, we have provided. concluded the basophilic aggregation I would like to know somebody who test of McCord has proven not only of is doing either or both of them, and if diagnostic but prognostic value. there is anyone here who thinks the We believe it to be a criterion show IX stipple cell count is very much better than the basophilic count, I would like ing reaction to degeneration as well as denoting the degree of regeneration. to know about it, because, if there seems I do not know how many of you agree to be a good reason to do it, we will go with me on that, but we have found back to it. At the present time in all the after about eleven years, since we have industries in Connecticut which have been using both the basophilic aggre any real lead exposure, part of the con gation and the stipple count, that a sig trol that we require of them is certain nificant rise in the basophilic aggrega medical control, part of which is a cell tion indicates an increase in the forma count. They can use stipple cells, if they tion of new cells, although some want to, but we recommend the other. basophilic degeneration of old cells is I would like to get some opinions on included in this count. that matter. At the present time we are When we see a patient showing a low running the basophilic cell counts, urine, lead in urine and porphyrin. Examina tion for porphyrin seems to be getting hemoglobin and red count with positive history of lead exposure, coupled with an increase in his stipple count, and if quite popular now. We have only been his basophilic aggregation increases, we doing it for a month. We are trying to feel, and our experience has taught us find out if we can get any correlation that we have adequate reason to feel 125 DUP050314481 126 DISCUSSION assured, that he is reacting physiologi cally. especially if he is under treatment. Another thing that I would like to say is concerning the stipple count. I would like to make an appeal for stand ardization in their enumeration. Nor mally, you know, we have anywhere from 15 to 60 oivmore stipples, or socalled basophils per hundred thousand red cells in the circulating human blood at all times. Aside from our views as to its importance in diagnosis and pathology, I make this appeal, inasmuch as we find in the literature, case reports and records of divergence of opinion as to the manner of enumerating stippled cells. We feel that, for expediency at least, we should come to an agreement in this matter. As regards the number per field, I did that for many years but found out, I believed, we were in error to a certain extent when we expected to establish the number of stipples in the circulating blood, while examining a few or even 50 fields, and noting the number per field. I felt that we ought to consider the fact that some fields contain more blood than others and, therefore, more stip ples, though admitting the fact that the film should contain, say, from about 150 to 200 red blood cells per field. Fre quently we see reports, [and to me it is rather amusing] such as rare, few, oc casional, many, so many per field, de creasing. increasing, 1, 2 or 3-f-> Class A, B or C, or one or more percent. These counts, I contend, are more or less confusing, inexact and misleading, and I think we should be as explicit in the stipple count as we are with our other tests which, by common usage and with more or less exactness we have learned to understand are recognized as standards. On this premise, I wouid like to ask if it is not more practical to use the more accurate and, furthermore, the simplest method, that one being used by most writers, of stating the number per hundred thousand or per million red cells. That has been uppermost in my mind for some time and I have been wondering why we do not standardize this thing. Of course, that is up to you gentlemen. Mr . G. C. Wa l t e r s [National Lead Co., Chicago, 111.]: Could I say a word here? There is one reason why the stippled cell technique has not been standardized and that is because we have microscopic light fields and dark fields, and until we come to a common objective as to which is the best sort of a microscope to use for it, I doubt if we will get together on any one particular stain, or technique. There has been a lot said about the Wright stain, but I have never found it en tirely satisfactory for the fight field work in stippling alone although it may be okay for other pathological blood work. It might be wonderful but we do not use the Wright stain in the fight field. In the dark field it may be better than any other stain. I do not know, because we do not use the dark field. Dr. Wilentz has used the dark field, and he might make some comment on it. I might say, while I am here that, as I stated yesterday, we compared the ag gregation count with the stipple count over a period of four years, running both. One time I tried to do both on the same slide, by fixing one half of the slide and not the other. It worked at times, and at other times it did not work. The only reason we gave it up was be cause of the staining qualities. The stain seemed to precipitate so by the end of the week, on the same man who was not exposed at all, we would get different readings. For that reason, we finally gave up on the basophilic count, al though there may he some of you that DUP050314482 B illfw, m ROUND TABLE 127 can use it to advantage, and, for those have an extra one during the war, and that can, I say "All to the good." I we found it almost impossible to get it found men, absolutely non-exposed, who together. You have to buy a regular ran above IV2 percent which McCord microscope, and then you have to buy allows, and even close to 2 percent, but special parts to it, to add to this. I can that man did not show any stippling. not tell you what it is because I do not Dr . Wo o d : Very likely you have the know myself. There are only one or two difficulty with your staips. These stains, fellows in the whole country who can I understand, must be made up fresh. put it together. One fellow left, and that Dr. L. E. Thompson of Washington left one fellow, and the company cannot University, does our blood work at the afford to fire him. [Laughter] St. Louis plant and makes his stains up Frankly, the truth of the matter is fresh each time. I think the secret of a that we have two scopes in one. We lot of the troubles we have been having use what you men all have, the ordinary with the basophilic aggregation is the microscope, and then we have the dark slain itself. I build a lot of faith on my field addition. They double check; both basophilic aggregation. As 1 say, I al counts are checked on the same scope. ways try to let the men know something In other words, my technicians check about it, when I see the basophilic ag themselves by the stipple counts and by gregation going up. If the stipples are the reticulocytes. They go hand in hand. up and the hemoglobin and red count We have had men come down and ob are down, I feel all right if the baso serve our set-up, which is a small set-up, philic aggregation stays up, but let that but where a lot of work is done. It is drop and the others continue down, die same old story, when they leave, then I know I will have trouble. everybody wants that scope. Mr . Wa l t er s : I wondered if Dr. We had a man come down here two Sappington would say something. weeks ago, the chief technician at the Dr . C. O. Sa p p in g t o n [Industrial Standard Oil Company at Bayway, New Medical Consultant, Chicago, 111.]: I Jersey. He no more than got back, in want to ask a question. I would like to fact he could not wait to get back to his get Dr. Wilentz to talk about what he plant, he wanted a scope like that. does with dark field with reference to Let me put it this way, to show you either basophilic aggregation or stippled there is a difference: each man in his cells. I do not know anything about own little bailiwick knows what he is dark field at all with reference to these doing. That is the answer; it is as ob 8 cells. I would like to know something vious as that. We happen to have this about ihein. particular scope. I do not say we know Dr . Wil l ia m C. Wil e n t z [National anything more than anybody else. But I Lead Co., Perth Amboy, N. J.]: I do this dark field scope permits us to see not know of what value I can he about more than what you would like to see this particular subject. The scope that sometimes. we use is a combination scope. It is two Dr . Gr a y : That is the trouble. I see scopes in one. You cannot buy it; you more in the light field than I want to have to put it together. It was developed see. [Laughter] by the Research Department of National Dr . Wil e n t z : The point is this: We Lead, and even all the various subsidi have a very wonderful comparison. You aries of National Lead do not have this take, for instance, a man that we have. scope available. For instance, I had to We sent him to the hospital that very j DUP050314483 128 DISCUSSION day. We had a count done on him in the morning at the plant. We sent him up to the hospital that very morning, and we had a count done in the hospital immediately. Although we know counts are variable, the counts taken, for in stance, in our hospital, by their techni cians and the counts done by my tech nicians at the plant being very different, I am not concerned about that. We take the worst count and play ball on that count. We get the worst count by our scopes, in other words, .we are not kid ding ourselves because we can't afford to. Mr . Wa l t er s : Our experience has been the same. Dr . Sa p f in g t o n : Yo u mean you get more in the dark field than the light field, a higher count? Dr . Wil e n t z : Sure. Dr . Wo o d : There is no comparison with the dark field in the detection of the Treponema. Dr . Wil e n t z : It looks the same, but a different bug. Dr . Wo o d : Could we have a diagram drawn, so we could build a correspond ing scope ? Dr . Wil e n t z : Sure you could but not with my help. You have to be a magician, and I am not kidding. Dr . Wo o d : I believe I can get Dr. Thompson of Washington University lo do it. Dr . Wil e n t z : This is a scope devised by the research department, on its own-- it would be more proper to say, "put together." Dr . Wo o d : It isn't hidden. We can look it up and get all the facts. Dr . Wil e n t z : Well, I don't know. There is no trade mark. It is a special thing made up. You saw the scope that was in Life, wasn't it, about the doctor in Chicago looking up the sludge. He made it himself, that microscope. It is possible; these fellows can do anything, but it is a very costly thing, by the way. I think the ordinary microscope costs $300 today. Mr . Wa l t e r s : Three to five hundred dollars. Dr . Wil en t z : I think, when you get through with the scope I am talking about, it represents about $800. I think that is approximately what it is. But that is not going to solve your problem. It is still prophylaxis. Dr . Go r d o n C. Ha r r o l d [Detroit, Mich.]: I wish we had the same situa tion of a man who cannot get fired. Since everyone cannot have that, and we do not have it, I would like to give you some of our struggles with some thing that everybody can have. What we are looking for is something that the physician can have in his office, and maybe in ten minutes make up his mind. I do not say it is the whole an swer; it is part of it, and, again, we are not making all-inclusive statements. It is something that needs a lot of work. I was talking to Dr. Mayers about coproporphyrins the other day, and she has had people from abroad who have been determining porphyrins in urine. Dr. Gray was talking about it today. It is in the air. I think that it is timely. It. is something that we all should look at very carefully. It may produce an an swer that all of us have needed; an answer to damage to the organism, and not to the transport of lead in the blood stream. I mentioned the other day, in a par tial answer, something that probably was not any answer. This complete article is going to appear, through the kindness of Dr. Sappington, in Industrial Medicine here in. December, 1948. Since it is for malized, it would, perhaps, be better for me to read it as it will appear. It will not appear as having been given at this meeting. Do not get me wrong on certain state- DUP050314484 URINARY PORPHYRINS 129 ments. Dr. Meek and I talked about por phyrins in 1937 and 1938. We did not have enough to go on then, and, more than that, we received some initial dis couragement from friends of ours who did not think it was quite the thing. It so happened that I have a friend who is probably the best man in chlorophyl in America, and chlorophyl, as you know, is only differentiated from hemo globin in the sense that you have a mag nesium ion or atom in place of the iron atom. Don't ask me to draw the struc ture for chlorophyl; that is tough busi ness; I guess it can be done; I know it can be. Abroad they have been experi menting with porphyrins a long time and 1 think they feel that it is worth a great deal. I am rather amazed it has not been timely enough in this country until recently. It seems that is one area where we have moved a little bit slower on than we should have. I will go on with this formalized paper. URINARY PORPHYRINS IN LEAD POISONING Py GORDON G. HARROLD, Ph.D. Consultant, Industrial Health, Hygiene and Safety Service, Detroit, Mich. Recently de Langen and ten Berg1 re ported on a simple semi-quantitative method for determining increased uri nary porphyrins in lead poisoning. Based upon a comparative examination of 87 persons with high lead intake in drink ing water and normal human controls taking pre-determined quantities of lead, these authors concluded their method of detecting abnormal amounts of urinary porphyrins was a more reliable early indication of lead poisoning than basophile granulation of erythrocytes. Salomon and Cowgill" have investi gated urinary porphyrins in lead-poi soned dogs and have concluded that dogs excrete increased quantities of uri nary porphyrins in lead poisoning as does man, but porphyrinuria in dogs is a late, rather than early manifestation. Incidentally, you get a different por phyrin in dogs, evidently, copropor phyrins that may be I and II and the coproporphyrin III. The research work is just coming up to date. That is one of our difficulties with this whole busi ness. An editorial in the Journal of the American Medical Association3 recently called attention to this interesting sub ject. It included a review of the work of Fischer et al who were responsible for most of our present knowledge of the structure and chemical relationships of the porphyrins. Fischer won the No bel Prize in 1930 for his work in demon strating various porphyrin isomers; his investigations were terminated by death in 1945. Also mentioned is the work of Watson4 and his group who have estab lished that 100 micrograms of urinary coproporphyrin per day is the upper limit of normal, about 80% of which is the Type I isomer and about 20% is coproporphyrin III. The amounts of coproporphyrin vary in different patho logic states as does the ratio of the two isomers. Particularly in lead poison ing, coproporphyrin III in the urine is greatly increased up to 8 mg. per day. The editorial previously mentioned3 cites Lhe theory advanced by Rimington6 to account for increased coproporphyrin III in the urine in lead poisoning. Rimington's theory is that the normal com bination of protoporphyrin with iron to form hemoglobin may be "blocked" by DU P050314485 130 HARROLD lead; the protoporphyrin which is un though it be much higher than the upper used is converted to coproporphyrin III limit of normal, it merely indicates ab and excreted in the urine. normal lead absorption, unless other Rimington's theory gained support findings in a given case enable one to when Vigliani and Waldenstrom (re make a clinical diagnosis of lead poi ported by Kench8) reported finding an soning." increase in blood protoporphyrin in lead Because quantitative analyses of urine poisoning and Vannotti and Imholz1 for lead are time-consuming and require found' an increase in non-hemoglobin specific, and for some methods, expen iron in lead poisoning. sive equipment and qualified personnel, However, Kench et als do not accept attention has been focused on the need the Rimington theory because they could for simple tests which will give an early not correlate quantitatively the copro indication of dangerous lead absorption porphyrin III excretion in lead poison or lead poisoning. The need is for sim ing with hemoglobin metabolism. They ple, inexpensive tests which can be per prefer the theory that lead in the blood formed in plants or physicians' offices stream is absorbed on the lipoid-protein by the industrial hygiene field worker film of the erythrocyte, and early de or the physician. struction of red cells in the peripheral Quantitative enumeration of baso circulation is, or gives rise to, stimula philic stippled erythrocytes has been tion of bone marrow. When consider found to be a fairly laborious and time- able lead is present in bone marrow, the consuming technique and one that is production of protoporphyrin for hemo not entirely specific, nor is the correla globin formation is inhibited. Thus, tion with clinical state and other tests Kench's group view decreased hemo satisfactory. I think the fact that we globin in lead poisoning as due to de talk about it and have to talk about it . creased formation of protoporphyrin so much indicates the uncertain state of rather than lack of its utilization. affairs. The basophilic aggregation test In most of the reference material of McCord,18 while no more specific, has given to this point, there is no attempt proved to be a valuable refinement; it to distinguish between lead absorption is relatively simple and saves time. This and lead poisoning;0 this distinction is test is particularly suitable for rapid important in any consideration of uri large scale survey work. Positive results nary lead content. Adequate urinary in individual cases can be valuable cor lead determination procedures, having a roborative evidence. Good correlation sensitivity in the order of one micro- between the basophilic aggregation test gram per liter, as used in the work re and urinary lead excretion has been ported herein,10 will indicate lead excre demonstrated10 in the case of certain tion specifically and provides a basis for lead salts soluble in human pleural fluid comparison with the accepted normal and blood serum. It does not correlate, range of urinary lead excretion in unex- as we have indicated,10 in "old" cases posed persons.8'10-11 It is believed that of lead poisoning. We have had a num correlation has been established between ber of cases that were given to us. We the lead content of 24-hour collections checked up on it and went through it. of urine and samples consisting of single I am sorry Dr. Fredrick has evidently voidings.10,12 However, the amount of had to make a train. I had hoped he urinary lead excreted per liter or per would discuss that because he has a lot day is just that and no more; even of additional information. DUP050314486 URINARY PORPHYRINS 131 The urinary porphyrins have been ples as were used to determine the por given considerable attention with refer phyrins were used in Column 2 but two ence to lead poisoning. The hope is ex drops of 3% hydrogen peroxide were pressed that as our knowledge of por added. The peroxide provides the same phyrin metabolism increases, a simple basic information under ultraviolet light test may be evolved which will give an as the samples without it but the inten early indication of lead absorption and/or lead poisoning. The following report does not reveal sity appears slightly increased and equal in all instances so that doubtful cases may he determined. It has been noted such a test, but it is hoped that it will that some samples which gave a faint aid in stimulating interest in this ap doubtful appearance of red phosphores proach to the problem. cence did not give this appearance with the H202. All samples in which the red EXPERIMENTAL or light pink fluorescence appeared with out question without the H,02 showed Single voidings of urine were ob the same, abeit slightly intensified color tained from 66 workers exposed to lead with the H202. fumes. The lead content was determined We, therefore, have relied in our on a portion of each sample.10 The semi- evaluation on the results revealed by the quantitative urinary porphyrin test of method modified by H202. de Langen and ten Berg1 wes performed It will be noted in Table I that 31 of on another portion as follows: 66 samples gave some degree of red To 20 cc. of urine, add 2 cc. glacial fluorescence and could be called posi acetic acid and 2 cc. ether and shake tive. It can also be noted that there is, briefly [I am sorry this paper does apparently, no great correlation between not point out the fact that we added the fluorescence phenomena in the case another cc. of ether because of the of the positive findings with the urinary 20 cc. of urine absorbing a certain lead content. That is probably an over proportion of ether and a certain simplification. There may be consider amount going off in gas.j; the test able correlation. tube is then examined under ultra This ratio of 31 positives out of 66 violet light. You do have a certain lead-exposed workers may be compared millimicron range here that you prob with the work of Franke and Litzner ably should hit, but it works under a cited by Watson4 who found that 17 out general ultraviolet light. We tried it of 43 lead-exposed workers gave urine out with a toy, and it worked beauti samples containing over 500 gamma co fully; just as well as it did with an proporphyrin III per liter, the range expensive instrument. The normal being 120 to 1,810 gamma per liter. The I urine subjected to this procedure will normal range of coproporphyrin III for reveal a light blue to green fluores unexposed persons was reported as 30 to cence in the ether layer. Urine con 70 gamma per liter of urine. taining large amounts of copropor There are some variations in this work phyrin III will exhibit a rose to deep that, have been reported by various in red fluorescence in the ether layer. vestigators. It is not conclusive, but I This data is shown in Table I, to think the indications are it will he a tool gether with the further data provided by that will he available which, when a modification previously used in other worked up, will be infinitely more valu work with porphyrins. The same sam able to us than basophilic aggregation DU P050314487 132 HAR.ROLD Table l Porphyrin Evtduation Porphyrin Evaluation modified by HtOs Urinary Excretion of Pb in mg. per liter Porphyrin Evaluation Porphyrin Evaluation modified by UiO? XJ rinary Excretion of Pb in mg. per liter LR............. . . . VLR . . . . . . BG . . . . . . . BG . . ,. . . . B ............. . . . B . . . . RR............. . . . RR . . RR plus . . . . . RR . . . . . . R ............. . . . R . . . . . . . BG............. . . .BG . . .. . . . B .... .. .. B ............. . . . B . . . . . . . 0.36 0.38 0 44 0.56 0.60 0.12 0.30 0.42 R?.............. . . . BG B .............. . . . B BG.............. . . . BG BG........... . . . BG B .............. . . . B R................... . . . R R?.............. . . . R BG.............. . . . BG R?.............. . . . BG . . .. . . .... . . . . ., . . ., . . . ... ... ... . .. . .. ...... .... .. 0.10 0.20 0.14 0.24 0.18 0.46 0.30 0.10 0.28 RR............. RRR .... B? . . . . RR.............. .... .... ". . . ... 0.32 0.42 0.20 0.12 B?.............. . . . VLR . . . . . . BG.............. . . . BG . . . . . . BG.............. . . . LR . . . . . . R .............. 0.32 0.44 0.44 R .............. RR.............. B? .... ... ... ... 0.24 0.26 0.46 R .............. . . . RR BG.................. . . BG BG.................. . . BG ...... ... ... ..... 0.50 0.36 0.81 BG.............. R? . . . . . . . 0.34 R .............. . . . R . . . . . . 0.35 . . . 0.32 RRR . . . . . . . RRR . . . . . 0.53 BG . . . . R .... R?.............. R?.............. ... ... .. . ... 0.16 0.86 0.12 0.10 R .............. . . . RR . . . . . . RR.................. . . RR . . . . . . RRR............. . . . RRR . . . . . B ................. . . B ... 0.40 0.51 0.61 0.15 BG ... . LR.............. . . . 0.16 B ................. . . B . . . 0.02 B?................. . . . R . . . 0.20 . . . . . . 0.25 B .... RR.............. RRR.............. ... ... ... 0.18 0.22 0.14, B B B ................. . . B ................. . . B ................. . . B ... ... ... ... .. . 0.24 0.37 0.23 BG................. . . BG ... . . . 0.22 B ................. . . B . . . . . . 0.28 BG . . . . . . . . 0.26 BG ..... . . . B . . . . . . 0.19 BG................. . . . 0.14 BG................. . . B . . . 0.20 BG................. . . . 0.16 R ................. . . RR ... . . . 0.52 LR . .............. . . LR : ; v . . . C.32 BG : ...... . . B . . . 0.31 RR ...... . . RR . . . . .: 0.14 RR................. . . RR . . . . . . 0.22 Symbols: B: Blue BG: Blue Green VLR: Very Light Rose LR: Light Rose R:Rose RIt: Strong Red RRR: Very Strong Red Note: Some of the values marked "BG5> actually had. a strong yellow fluorescence but in view of the fact that this phenomena was negative as regards the light rose colors, these few values were included as "BG's." DUP050314488 If IS fR tB' I. URINARY PORPHYRINS 133 or stippling methods and, certainly, it will be an additional tool. Watson1 reported normal copropor phyrin III in urine of unexposed indi viduals as ranging from 1.4 to 34.3 gamma per day. The results published by Kench3 are of a lower order; he re ported on 12 lead-exposed workers whose average urinary lead was 292 gamma per liter with a range of 182 to 436 gamma per liter; the average copro porphyrin III content of the urine was at the rate of 88 gamma per liter with a range of 16 to 343 gamma per liter. Kench did not demonstrate direct corre lation of urinary lead with copropor phyrin III. Schein14 would indicate that 50 gamma would be the high upper limit for copro porphyrin III per liter of urine. The fluorescence phenomena is quite sensi tive and will appear below this range. Experimental data correlating fluores cence with coproporphyrin III is not available to us at the present time. SUMMARY The rapid evaluation of present or potential lead intoxication by means of the determination of porphyrins in urine is subject, as is stippling or basophilic aggregation to the influence of a num ber of other chemicals. However, it is not directly dependent on any blood discrasia and is much more likely to be indicative of lead intoxications which are not dependent on anemias. It, there fore, represents potentially a laboratory tool which can represent with much greater fidelity the various forms of lead intoxication than could stippling meth ods. Finally, it should be noted that we are relating a phenomena which may be much more indicative of damage than either the amounts of lead in blood oxurine which, at best, represent an indi cation of the transportation of lead in some form or another throughout the organism. BIBLIOGRAPHY ' de Langen, C. D., and ten Berg, J. A. G., "Porphyrin in Urine as First Symptom of Lead Poisoning," Acta Med, Scatidinav., 130, 37 (1948). (Abs.JM.M.A., 138, 244, 1948). s Salomon, K., and Cowgill, G. R., "Porphy rinuria in Lead-Poisoned Dogs," J. lad. Hyg. & Tox. 30, 114 (1948). 3 Editorial, "The Significance of Urinary Co proporphyrins," J.A.M.A., 136, 627 (1948). * Watson, C. J., and Larson, E. A., "The Urinary Coproporphyrins in Health and Dis ease," Physiol. Rev., 27, 478 (1947). 5 Rimington, C-, Compt. rend. d. trav. da lab. Carlsberg, serie chim., 22, 454 (1938). "Vigliani, E. C-, and Waldenstrom, J., Deatsch. Arch. f. klin. med., 180, 182 (1937) (As reported by Kench). 7 Vannotti, A., and Imholz, A., "Die Beziehon gen des Reticulumendothels Zum Umsatz des Nichthamoglobineisens," Z. ges. exp. Med. 106, 597 (1939). 3 Kench, ,T. E., Gillam, A. E., and Lane, R. E-, "Haemopoiesis in Lead Poisoning" Biochem. /., 36, 384 (1942). " Occupational Lead Exposure and Lead Poisoning, American Public Health Associ ation Report of the Committee on Lead Poi soning of the Industrial Hygiene Section (1943). 10 Meek, S. F., Collins, G. R. and Harrold, G. C., "Correlation Coefficient Between Baso philic Aggregation Test and Lead in Urine," J. Ini. Hyg. & Tox., 22, 401 (1940). ,lKehoe, R. A., Thamann, F., and Cholak, J., "Normal Absorption and Excretion of Lead," J.A.M.A., 104, 90 (1935). 77 Barnes, E. C., "Possibilities of Control of Lead Exposure by Examining Less than 24 Hour Urine Samples," J. Ind. Hyg. & Tox., 21, 464 (1939). 13 McCord, C. P., Holden, F. R-, and Johnston, J., "Basophilic Aggregation Test in the Lead Poisoning Epidemic of 1934-1935," Am. J. Pub. Health, 25, 1089 (1935). 14 Schein, U., "Zum Nachweis der Porphyrinuric bei Bleier Kraukungen" Arbcitsschultz, pp. 336-339 (1943) ; Chem. Zentr., 2, 46 (1944). mm DUP050314489 134 DISCUSSION Ch a ir ma n Bo w d it c h : I might com ment on this very interesting discussion of Dr. Harrold's by saying that he showed me this paper two weeks ago or so, when I was here in Chicago, and I conceived the idea that it might be made the basis of a little symposium here this afternoon, on the subject of porphyrins. I discussed it with Dr. Mayers and found that she was extremely interested. I discussed it by telephone with Dr. Aub in Boston, who suggested that I get in touch with Dr. Karl Dohriner at Me morial Hospital, which I did, and had a little session with him. He suggested that I get in touch with Dr. Watson at the University of Minnesota. I tried the next morning to reach him at Minneapo lis and wound up by reaching him in Richmond, Virginia. He was extremely interested and enthusiastic, but found it impossible to be here because of an unbreakable prior engagement. Of course, the whole thing was on very short notice, but, from my conversations with these individuals who are experts in the field, there is no question in my mind that there will be no diffi culty whatsoever in pursuing the matter further. Dr. Mayers, would you care to com ment on the subject? DISCUSSION Dr . Ma y R. Ma y e r s [New York State Department of Labor, New York, N. Y.] : I do not feel as though I really know anything about it. I am greatly in terested but, beyond that, 1 do not know that I have anything to contribute at this stage. Mr . G. C. Wa l t e r s [National Lead Co., Chicago, 111.] : Could I ask Dr. Harrold what he used on his urine lead, in his talk yesterday, and how it compares in time and complexity with the por phyrin that you just talked about now? Have you compared the two? Dr . Ha r r o l d : You mean you want me to tell you how fast we can do urinary leads, or how slow you can do these porphyrin tests? That is an inter esting topic. We do have certain thoughts on that subject of what you can do, how fast and how many. You have certain choices with Cholak's spectrographic method. You can test up to 40 urine samples a day. I do not think you can do move than that, and with the polarograph and with a good man doing the work, you can analyze, perhaps, 50 urine samples a day for lead content. With the dithizone method we pub lished some time ago -- the method that we use -- we are stuck with it; with that method which was published back about 1937, 1938, or something of that sort -- we have been using it since 1935 or 1936 --we cannot analyze more than 25 samples a day, and that takes a good man working a little overtime on his eight-hour shift. Even good men do not like to work more than eight hours. But this method you can probably complete in less than fifteen minutes, and all you need is a test tube and a strong right arm. I have tested over 100 samples in eight hours. Dr . Gr a y [Director, Bureau of In dustrial Hygiene, Connecticut Depart ment of Health, Hartford, Conn.]: You don't need a very good technical man either, do you? Dr . Ha r r o l d : No . Once you set up your chart, anybody who can read could do a pretty good job on the thing. That has some obvious merit. It may not he DUP050314490 PP URINARY PORPHYRINS 185 the final answer, but I think that it will another band at 357, but for the copro add tremendously to our knowledge. porphyrin III, it is about 401. It may 5ut I think we need to review the fact not be to your advantage to want to that, in our various laboratory artefacts complicate this kind of thing. If you -- I am not a physician, my partner is could set up a sound basis to do the test -- we determine laboratory artefacts, and that is all they are. Who was it said -- I believe it was Dr. Eagle -- a rabbit is a rabbit is a rabbit, and you in the office on a basis of a gradation of six different degrees, from where there is "nothing," or "up to something," or "very strong," it may be that that is as cannot change that. In determining lead far as you want to take it. in urine, it is lead in urine, but as to So far, all the work that has been whether it hurt anybody in getting there, done, in trying to make it extremely ac I do not think we know a thing and that curate, on a fully quantitative basis, has is what we want to know. I think the led to quite a lot of variations in the porphyrins will tell us whether somebody amounts of coproporphyrin III that are got hurt, when that lead was going determined by various investigators. through the organism. There is another point. The fluorescent >w I wanted to emphasize something that phenomenon is more sensitive than Warren Cook said. Determine lead in many others, and you have difficulty in urines, and keep on using the method forming test compounds, which is just because it does provide a good yardstick like that of dithizone utilization. It may on certain operations in the plant, when be beLter not to do those things. You you are doing operational control and certainly do not have to get the kind of building your safeguard, so you will not data we were putting together. have any sick people. While you are I presume, Dr. Gray, you have been i doing that, your lead in urines do help, doing something like that. and are an added factor in your engi Dr . Gr a y : Exactly. i neering control. In that sense, I think it Dr . Ha r r o l d : Dr. Fredrick and I see is perhaps as important as it is in your each other at meetings, and he has told is diagnostic data. Does that answer your me some of the things he has tried. I question ? even see Bill Witheridge at meetings. Mh . Wa l t er s : Very good. Dr. Fredrick was telling me about what Dr . J. M. Le o n a r d [National Lead he has done. He has taken some samples Co., Chicago, 111.]: Do you use a Wood's which he can read in the daylight, with filter? out the fluorescent phenomenon. They Dr . Ha r r o l d : No. start getting red in the ether layer. I Dr. Watson, whom Manfred has men suspect that would go high in our six- tioned here, is really, I think, the dean degree range. The ones we found ex a. of all authorities in this country and tremely strong were in that category. M: has done sound, solid, back-breaking Dr . Le o n a r d : Does your entire ether a| work, and he probably knows more layer fluoresce? about it than anybody in this country Dr . Ha r r o l d : The whole ether layer and perhaps as much as the three or will fluoresce, and the other material four or five outstanding experts in vari below that will fluoresce. Urine will ous other countries. fluoresce a yellowish or greenish type You do not have to use a Wood's of color. The phenomenon of that light filter. It is true that you get an ideal yellow means something. I do not know band at 401 mu.'s, and then there is what it means. Whether it is bismuth. Jg DUP050314491 136 DISCUSSION and we have a tip-off, as we do in the dithizone action or some other organic material is present, is uncertain. It is an interesting sidelight. Dr . Jo h n E. Sil s o n [New York State Department of Labor, New York, N. Y.] : Aren't coproporphyrins stable, so you could make up standards containing measured quantities and use them for comparisons? Dr . Ha r r o l d : Yo u can, but I have not done it. It is a tough job. What you do is to break down your hematin, and hematin, broken down, goes into por phyrins and you get a certain amount of coproporphyrin III and copropor phyrin I, and at least eight other cop roporphyrins. You form your methyl esters then. After you have done the separation technique, you take the methyl esters back, and you can get your coproporphyrin III. It is not an easy job but it can be done. The original work was done the hard way, by taking hundreds of gallons of urine, and some people took blood, and various methods of getting breakdowns, and going at it in a pioneer way. That part is established. It is now a matter of applying some of the things rve know, and pushing ahead. In my opinion, the step is short. I do not think we have to go loo far before we have something fairly decent, and the next year should produce a reasonable answer. Mr . Wa l t e r s : Will your paper be available ? Dr . Ha r r o l d : It will be published December 15. Dr . Sa p p in g t o n : About that time, in Industrial Medicine. Ch a ir ma n Bo w d it c h : Is there further discussion of this subject of die porphy rins? Dr . Le o n a r d : I would like to ask a question. Has anyone used the spectro graph in the determination of lead in urine. Is it reliable, and can we use it? Ch a ir ma n Bo w d it c h : It is not used widely, 1 believe, and my knowledge of its use is very limited. Dr . Le o n ar d : We have used it on one sample. I took just a single specimen from one of our boys who has persistent ly shown a fairly high stipple cell count. Our man over at the plant took a drop of this urine, dried it out and sparked it under the spectrograph, and he got a very beautiful red ink, and he just estimated the number of gammas of lead per liter that that urine would be. It is simple. It certainly is a simple thing to do. It only takes a few minutes. I wonder why there hasn't been some thing more done about it. I would like to see some work done on it, and maybe, it could help clarify all this controversy about quantities, amounts and all of that. Dr . D. J. La u e k [Kettering Labora tory, University of Cincinnati, Cincin nati, Ohio]: I just want to say that Cholak of the Kettering Laboratory has been using the spectrograph for the determination of lead and other trace metals in many types of biological ma terial, including samples of urine of large and small volume. He has been using a spectrographic method as a check method on the dithozone method for years and has published extensively on it. Certain other investigators are using it, too. The methods are satisfac tory and are available to those who have proper equipment and adequate technical training. Ch a ir ma n Bo w d it c i-i : I might add this comment to the question that was raised a little while ago with regard to the standardization of stippled cell count ing in connection with the work of a subcommittee of the Z-37 Committee of the American Standards Association. I wrote to the other members of this subcommi-tee last June, suggesting that two questions be taken up by the main committee, one being that of establish- DUP050314492 URINARY PORPHYRINS 137 ing separate atmospheric standards for the various compounds, or some of the various compounds of lead on the basis of their known greater or less toxicity, and the second one being the question of establishing standards for stippled cell counting. The replies varied very greatly. I had them mimeographed ahd sent them out, in turn, to some 20 or more authorities throughout the country, asking for their views, and those, in turn, came back. I should say I had somewhere between 25 and 30 replies in all. There was no uni form support for the idea of trying to work out standards for stippled cell counting, and I got all kinds of replies on the question of standards for the various lead compounds, which boiled down to two main schools of thought. One was to the effect that we should let well enough alone, even admitting that there was a tremendous variation in tox icity, and that the 1% mg. Per 10 M3 was so well established that we might as well hang onto it and let it go at that, leaving any questions of discrepancies in toxicity to the intelligence of the indi vidual industrial hygienist. The other school believed that we definitely should do what I proposed, and that we should do it as immediately as possible. They were equally divided. There was also a sub-school that felt that we should set up these separate standards, but only after further and careful research. So that is where the matter rests. I used these opinions as a basis for my part in a panel discussion at the A.P.IT.A. in Boston last week, and the comment I got there again indicated a quite sharp division of thought on the subject. I mention this only because lead is interesting to all of us here and, like the woman convinced against her will, 1 am still of the opinion that it is illogical to use the same standard for galena that we do for lead oxide. I believe that Dr. Mayers was of the school that thinks we should let well enough alone. Would you care to com ment on this, Dr. Mayers? Dr . Ma y e r s : I think it is a very in teresting subject. My principal reason for wanting to let well enough alone, is that I feel you are dealing not only with differences in chemical formula: but with differences in physical proper ties, and operational factors as well. So, you have several variables, and we do not know very much about any of them. We do not even know too much about differences in permissible standards on die basis of the purely chemical for mulae alone. So I feel that, to be wandering out into this great unknown, would not be very helpful. Why not drerefore just leave it as it is until we get more in formation? Perhaps some time in the future it might be a good idea to do something. But we are dealing with at least three variables about which we know very little; and any one of which can swing the picture, outbalancing the other two. Even operational factors are uncertain in terms of quantities used and the many and varied conditions of exposure. I believe we would be just wandering into a field where we would really have very little scientific data to guide us. Ch a ir ma n Bo w d it c h : Are there any further comments on this subject? If not, I will declare the Conference at an end. Thank you very much. m DUP050314493 DUP050314494