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INDUSTRIAL POISONS IN THE UNITED STATES
THE MACMILLAN COMPANY NEW YORK - BOSTON - CHICAGO - DALLAS ATLANTA + SAN FRANCISCO
MACMILLAN & CO., Liwitrep LONDON + BOMBAY -« CALCUTTA MELBOURNE
THE MACMILLAN CO. OF CANADA, Lip. : TORONTO
INDUSTRIAL POISONS Py THE UNITED STATES
BY ALICE HAMILTON, A.M., M.D.
Assistant Professor of Industrial Medicine, Harvard Medical School, Boston, Mass.; Formerly Special Investigator of Poisonous Industries for the U. S. Bureau of Labor Statistics
jQew ork THE MACMILLAN COMPANY 1925
All rights reserved
CopyricHt, 1925, By THE MACMILLAN COMPANY.
Set up and printed. Published May, 1925.
Printed in the United States of America by J. J. LITTLE AND IVES COMPANY, NEW YORK
CRD
Tux sources of our knowledge of industrial poisoning in the United States are neither full nor, for the most part, accurate. We lack the sickness insurance system which obtains in all industrial countries in Kurope and which brings to light the incidence of illness of all kinds in all groups of workers. Nothing takes its place in this country. Our private insurance companies sometimes gather important and trustworthy data, but these are never all- inclusive and never can be, they are always restricted to the group of individuals insured in that company. The Census reports are of deaths only, not illness, and the death records lose much of their value because of a poor classification of workers, which puts into the same category men doing work of very different degrees of danger, as for instance paper-hangers and painters. Trades union records are sel- dom of value, with the exception of those gathered by the typograph- ical unions which were reviewed carefully by Verrill* and found to contain much that was interesting to the statistician.
It has been my task for many years to examine records of hos- pitals and dispensaries and to interview physicians in many parts of the country in my search for information about a given poisonous trade. Not one hospital in twenty has records which yield the sort of information which the student of industrial toxicology craves and yet this is not elaborate. If the recording interne would only treat the poison from which the man is suffering with as much interest as he gives to the coffee the patient has drunk and the tobacco he has smoked, if he would ask as carefully about the length of time he was exposed to the poison as about the age at which he had measles, the task of the searcher for the truth about indus- trial poisons would be made so very much easier. I have often had to reject fully one-third of the cases of plumbism which have been treated in a hospital because the interne had no curiosity about the source of the lead, contented himself ‘with the notation, “lead worker,” and so made it impossible for me to know from which of the many lead trades the man came.
Physicians in private practice have given me the greatest assist- ance, yet there are limitations to the value of the information obtained in this way. The diagnosis must be accepted, of course, as the Bureau of the Census accepts the death certificates of all
* Hygiene of the Printers’ Trade, A. Hamilton and C. N. Verrill. Bull. 219, Bureau of Labor Statistics, Washington. 1916.
i
3869
vi PREFACE
physicians, but mental reservations may have to be made. One must always remember in a study of this kind the existence of a prejudice which may cloud the mentality of some first-class men. Apparently it is impossible for some physicians to treat industrial diseases with the detachment and impartiality with which they approach those diseases which are not confined to the working classes. For a strik- ing example of this the reader is referred to a bulletin issued by the Bureau of Labor Statistics on a trade disease—not an intoxica- tion—in stonecutters.* The evidence is given from a doctor who worked for the stonecutters’ union and from two who were brought in by the employers. Not only is there the widest divergence of views presented, but the physician who was retained by the men shows so strong a sympathy for them as to quite dull his critical sense, and the physicians for the companies accept evidence which is on the face of it one-sided, and then indulge in moral observations on the character of workingmen and the evils of trades-unionism.
Another drawback to the obtaining of information from physicians is the fact that, since the passage of workmen’s compensation laws, almost every plant in which poisons are handled now has its own physician and he is often unwilling to give out facts which may seem damaging to the company. On the other hand I have often had all the records laid frankly before me and been permitted to make what use I pleased of them.
No source of information should be despised. Apothecaries, visit- ing nurses, undertakers, charity workers, priests, often let drop valuable leads. The statements of the men themselves should be treated with respect, and checked up, and often they will prove to be founded on close observation. or instance, down in the copper region of Arizona I was told of cases of profound anemia and loss of strength among men engaged in the electrolytic production of copper, and when an examination of the premises showed no ground for this I was inclined to reject the tales, but closer study showed that in connection with this method there is always the possibility of arseniuretted hydrogen poisoning, if the copper carries some arsenic as it often does, and slow poisoning from this gas would bring about just such a condition as that described. The statement of some men in a white lead plant, that there was a good deal of plumbism among the men who made the blue bed, seemed to me exaggerated, because such men handle only clean lead buckles, but when I investigated I found that remnants of old corrosions were mixed with the latter, scraps covered with dusty white lead, and this was enough to account for the cases.
European literature is of enormous value for the physiological effects of a given. poison and the mode of entrance, but it can tell us
* Effect of the Air Hammer on the Hands of Stone Cutters. U.S. Bureau of Labor Statistics. Bull. 236, 1918-19.
PREFACE vii
nothing about the probable incidence of poisoning in American industry because our methods differ decidedly from the European. Some trades which are dangerous there are quite harmless here. For instance, the making of cheap kitchen ware is one of the bad lead trades of England, here it is not a lead trade. Dyeing cotton and wool and handling them after dyeing, making files, polishing diamonds, these are occupations notoriously fraught with danger of lead poisoning in Europe, but not in the United States. On the other hand we have industries which are much more dangerous than theirs, such as the making of white lead by a dry process instead of a wet one, the use of large quantities of non-fritted white lead in pottery glazing, and the use of lead-laden enamel powder for sanitary iron ware. It is not possible to draw conclusions as to the danger of any occupation in the United States by simply con- sulting the foreign literature about it.
There has been an enormous increase in the interest of the medical world in industrial toxicology of late years, especially since our entrance into the war in 1917. There are already some studies of poisonous trades in the United States which for thoroughness leave nothing to be desired. Perhaps the study made by Edsall, Wilbur and Drinker * on manganese poisoning stands at the head of these, for they were able to study the incidence in a large group of work- men, the conditions under which poisoning occurred, the mode of entrance, and the clinical manifestations, of early stages of poison- ing as well as of the later stages.. At the foot would stand the single observation made by a physician in private practice on a _ ease occurring in a plant to which he has no access and the descrip- tion of which he must take from his patient. He cannot check up his findings, he cannot be certain that this, to him new and unfamiliar poison, is really responsible for the lesions he has _.observed; all he can do is to present his findings, suggest their possible significance and let it go at that. But he is really per- forming a valuable service when he does this, for such reports, incomplete as they must be, have often led to the exploration of a new and important field of industrial toxicology.
I have called this a study of industrial poisoning in the United States and have tried so far as possible to present American material, but obviously that is not always practicable and much that we owe to foreign observers has had to be included. It has been my pur- pose to avoid when I could the earlier writings which have been reviewed in the existing textbooks and to give as much new mate- rial as possible. The literature up to January 1, 1924, has been included.
* Edsall, D. L., Wilbur, F. P., and Drinker, C. K. The Occurrence, Cause
and Prevention of Chronic Manganese Poisoning. Jour. Indust. Hyg., 1919-20, I, 183 3
CONTENTS
PREFACE .
CHAPTER
‘1, Iyrropuctrion to InpustrriAL Toxicology
2. Leap: ParHoLocy
3. Leap: AsBsoRPTION AND ExorRETION. QUANTITY
4. Leap: Conic. ARTHRITIS .
5. Leap: Patsy
6. Leap: ENCEPHALOPATHY
%. Leap: DrtraAanosis
8. Leap As A Race Porson . BU cd me
9. Toxicrry or Leap Compounps. Compounps Usep 1n In- DUSTRY ‘Lae ogee ae
10. Leap Mintne. Leap Smevttine AND REFINING. METALLIC LEAD Ra eR ig 2g! Sag 5g ing eee. Aig. penniy
11. Tue Prinrers’ Trave
12. Wuire AND Rep Leap. SrorAGE BATTERIES
13. GLAzes AND ENAmets. THe Porrery TRADES
14. THe Painters’ TRADE
15. Miscer.anrous Leap TRADES
16. ARSENIC
17. Mercury
18. THe Harrers’ TRADE
ig Wnass wk
20. Mancanese. AntTIMoNy. CapmMiumM. Nicks, CARBONYL .
21. Setentum. TreLLURIUM. VANADIUM. PHOSPHORUS
22. Caustics. AMMONIA. CHROMATES :
23. SuipHuric Actp. Hyprocuioric Acip. PHOSGENE
24. Nuirric Actp. Hyproriuoric AciD
25. HyprocyAnic Actmp AND CyANips. CYANOGEN CHLORID. Catcium CyYANIMID Gs her ath ue ge gg ae
26. Hyprogen SutpHip. Carson DISULPHID
ix
110 116
124 140 163 173 185 201 206 234 254 276 291 = 303 © 317 323 335
344 354
x
CONTENTS
CHAPTER
27: 28. 29. 30. 31.
32.
33. 34, 35. 36, 37. 38.
CarBoN Monoxip. Mine GASES .
PETROLEUM DISTILLATES Pe ae enue eae a Or. Forunocuiosis 4np Tarn Canoge 3: 3“. 4. oP eee Merrry.t. AINOHOL “Oo ee ee See ee
Erner. ALDEHYDS. HEXAMETHYLENETETRAMIN. METOL. AMYLACETATE. DIMETHYL SULPHATE. .... .
MetuHyt, CHiorip. TrrRACHLORMETHANE, TETRACHLOR- ETHANE, OTHER CHuLorR ComMpounps, Metuyt Bromip, NITROGLYCERIN eee? cemetery
DBONSINE «600 6 a SS AS Bek ae ee BENgen® DEkivyATIVEs. 2. = so ex hc a ieee ‘Tar CosL-Tan Dye Inpoerey . oo.) oe See Tue Ruspper TRADE gi et ial Pe iets a es er Torrentring; Topko00e 20s 0. a eee
THE PREVENTION OF INDUSTRIAL POISONING. ... .
PAGE
371 400 410 418 ©
429
441 453 483 512 523 533 538
INDUSTRIAL POISONS IN THE UNITED STATES
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IN THE UNITED STATES
CHAPTER 1 INTRODUCTION TO INDUSTRIAL TOXICOLOGY
Chronic, Not Acute.—Industrial poisoning is typically chronic, the acute forms are relatively rare, although this is not as yet so true of industrial poisoning in the United States as it is in most European countries. Protection of workers in the dangerous trades in. Amer- ica is still fragmentary and incomplete and it is still true that men may be exposed to much more massive doses of a trade poison than is permitted in the older countries. We have in the United States a larger proportion of acute cases of poisoning from lead, benzene, anilin, petroleum distillates and methyl alcohol than occur in Great Britain, Germany or Holland. But even here the chronic cases, though less spectacular, are much more numerous and usually more serious than the acute. A man may die of acute benzene poisoning, but if he survives the heavy dose he recovers completely. Chronic benzene poisoning means aplastic anemia with purpura hemor- rhagica, and if the man survives that, it is impossible for us to say, in our present state of knowledge, that he can completely recover - normal health. The danger done by repeated small doses of lead is lasting, that done by one short exposure to heavily contaminated air is probably transient and leaves no permanent damage.
Mixed Poisons.—The diagnosis of industrial poisoning is. likely to be rendered more difficult by the fact that the worker is so often exposed to more than one poison and the clinical picture is not clear-cut and typical. In zinc smelting the fumes contain zine oxid, cadmium, lead and arsenic. Printers and rubber compounders come in contact with antimony as well as lead, but it is impossible to say how much of a réle the former plays in the illness that ensues. Painters breathe fumes of benzene, wood alcohol, petroleum ether, amyl acetate, and still other volatile solvents. Makers of surgeons’ rubber gloves breathe benzene and carbon disulphid. As for workers in coal tar dye manufacture and in the chemical trades, there is a bewildering number of toxic substances with which they may
1
2 INDUSTRIAL POISONS IN THE UNITED STATES
come in contact. A man engaged in producing the color auramin runs the risk of poisoning not only from a number of coal tar intermediates but from ammonia gas and sulphuretted hydrogen as well.
It is not enough to know what substances the patient has met with in his work, one must know also what sort of work goes on in his neighborhood. I have known two rubber workers who did not handle lead at all, but who acquired plumbism from the dust that rose from a neighboring mixing mill, and the fact that the mill men were apparently unharmed by the litharge dust naturally obscured the situation. A man engaged in the nitra- tion of benzene became severely poisoned by the fumes of dinitro- benzene from some cooling pans near by, and a girl labeling paint cans in a clean room became poisoned by white lead dust which some- times blew in through a door from an open chaser for the mixing of white lead paint.
There are several important factors which influence the incidence of industrial poisoning to an extent not always appreciated, some of which concern the worker himself, others the conditions under which work is done.
Hot and Humid Air.—Heat accelerates chemical action, and therefore accelerates the action of poisons. Heat facilitates the absorption of those poisons that pass through the skin, for a hot atmosphere flushes the surface blood vessels and causes profuse sweat- ing. During the war it was very evident that cases of trinitro- toluene poisoning increased regularly whenever the weather was hot and humid (1). In one very dirty and neglected shell-loading fac- tory, where direct contact with trinitrotoluene was absolutely unavoidable, there were during six days of normal summer weather, with the thermometer between 68 and 88 degrees F., only four men who sought treatment for “TNT sickness,” but during six days of heat above 90 degrees F., there were twenty, nor did this represent the full number of cases of sickness, for during that hot spell hardly more than a third of the force reported for work.
The same thing is found to be true in anilin dye manufacture. There is invariably much more trouble, not only with anilin but with other intermediates, such as dinitrobenzene, the nitranilins, the nitrochlorbenzenes, the phenylendiamins, etc., in hot, moist weather than in cool, dry weather. In the summer of 1916, when the manufacture of intermediates was still in an experimental stage in the United States, one factory which produced dinitrochlorbenzene for sulphur black was obliged to close down because the men were practically all suffering from a distressing trade eczema. The German factory inspection reports covering the war period (2) show the effect of heat in increasing the cases of poisoning from dinitro- benzene, so largely used in their high explosive shells. In one plant
INDUSTRIAL POISONS IN THE UNITED STATES 3
the cases of “DNB” poisoning averaged only 2.3 per cent for the cool autumn months, but 30.8 per cent for the summer months. So striking was the effect of heat on the incidence of poisoning that Koelsch, who was in charge of the Bavarian factory inspection department, succeeded in inducing one factory to have all the DNB work done before ten in the morning and after three in the after- noou, using the early and late cool hours.
Long Howrs.—W ithout entering into the controversy as to whether fatigue lowers the resistance to poisons, it is safe to assert that long hours of work increase industrial poisoning simply because they
- imerease the actual dose of poison and also lessen the chance of
completely eliminating one dose before another is taken. It is obvi- ous that a man will absorb more poison in ten hours than in eight hours or in six and he can eliminate more in sixteen hours than in fourteen. Observations that were made on TNT workers during the war showed that when there was not enough time between the shifts of work for a man to eliminate the TNT he had absorbed, the amount would accumulate and on Friday larger quantities would be appearing in the urine than on Monday. Repeatedly it was found that the urine when tested for the so-called Webster reaction would give a negative result after a holiday, a positive result at the end of the first eight-hour shift, and a reaction of increasing intensity as the week went on. ‘The value of a short working day, the danger of overtime work and of the seven-day week, was shown clearly by these observations. It was also found that while some men could eliminate over night what had been absorbed during the day and others could get rid of the week’s accumulation during Sunday and start on Monday with the urine free from the reduction product of TN'T, which is shown by the Webster reaction, there were others who required a longer time, and that true economy would dictate the granting of several days holiday from time to time for over-susceptible workmen, as was done in Great Britain toward the end of the war.
The combined effect of long hours and heat was seen in one of the TNT shell-loading plants in the summer of 1916. June of that year was cool, work was not rushed, and during that month shell loaders worked only eight hours, then came a rush order with over- time, the men working ten, eleven, and twelve hours, even sixteen hours occasionally, for the high wages induced some to work two eight-hour shifts in twenty-four hours (3). This continued through the hot weather of July and August, the plant being situated down in Delaware in low, flat country. The cases of TNT poisoning during June numbered 23, in July the number was more than double, 55, and in August it was just trebled, 69. The cool of September and the slowiug down of work brought the cases down to 36.
4 INDUSTRIAL POISONS IN THE UNITED STATES >
Food.—It is, of course, a fact well known to pharmacologists that drugs are absorbed more quickly by the fasting stomach than when administered after a meal, but although almost anyone knows this to be true with regard to medicines, few people realize that it is equally true with regard to industrial poisons. Experience in the lead trades taught the English years ago that one of the best preventa- tives of lead poisoning was the presence of food in the stomach, and in English lead works it has long been customary to supply the workmen, free of cost, a glass of milk or a cup of cocoa the first thing in the morning, and in their more recent industry of anilin dye manufacture the English follow the same rule. The Germans’ experience during the war, when the food blockade demonstrated’ on an unprecedented scale the effects of lack of food, has proved conclusively that lowering the body nutrition results in a marked lowering of the resistance to poisons.* In spite of the increasing knowledge as to the prevention of poisoning from various explosives which was gained as the war went on, the number of cases of poison- ing increased in Germany as the food blockade tightened, instead of falling as it did in Great Britain, in France, and in the United States. In the Diisseldorf-district the deaths from DNB poisoning in 1915 were only 7 among 1,603 workmen, or 1 in 230, in 1916 they had risen to 10 among 1,516, or 1 in 150, and in 1917 to 25 among 2,000, or 1 in 80.
This question of the influence of proper and sufficient food in warding off industrial poisoning has received less attention in the United States than one would expect. In all my experience I have known of but one white lead works and one anilin dye works which give milk to the workmen, and in the case of the dye factory it is given only to those employed in the most dangerous department, the one in which dinitrobenzene is handled. It is not usual even in the poisonous trades to find provision for a wholesome hot meal at noon, and the indigestible cold lunch is as customary in American factories where poisons are used as is the lunch room with hot food | and hot tea or coffee in the German and the British factories.
Carlson’s and Woelfel’s (4) experiments with the solvent action of human gastric juice on the basic carbonate of lead and the basic sulphate confirm the practical experience of the British that milk or other food in the stomach minimizes the danger of lead poisoning from the digestive tract. They found that when milk and gastric juice are mixed in the proportion of one to one, lead salts added and the mixture incubated at body temperature for 10 hours, not enough lead goes into solution to give a qualitative test for lead (with two exceptions when white lead paint dust was used). The
* Aducco found that starvation increases the action of cocain, strychnin and phenol; Jordan, that starvation increases the action of digitalis. (Kobert, p- 26.)
INDUSTRIAL POISONS IN THE UNITED STATES 5
same results were obtained in mixtures of hydrochloric acid 0.05 per cent and milk. But when the ratio of gastric juice or HCl to the milk was increased, the lead salts were dissolved in proportion
_ to the increase in the quantity of gastric juice or HCl.
“This action of the milk is probably due to the fixation of the HCl by the milk protein and the neutralization of the HCl by the carbonate of milk. Hence when an excess of milk is added to the gastric juice there will be no hydrochloric acid to effect solution of the lead salts, while in the presence of an excess of gastric juice some free hydrochloric acid remains to act on the lead. We are inclined to the view that the formation of insoluble lead albuminates is a factor of minor importance in the above action of milk.... Albuminous foodstuffs can therefore diminish the solution of lead salts in the stomach only to the extent that they fix the HCl in the gastric juice. . . . The taking of milk is a more eflicient prophy- lactic measure than the taking of an equal amount of other forms of proteins, because there is less appetite secretion of gastric solu- tion with milk and the fat in the milk depresses and retards the action of the gastric secretagogues.”
Carlson advises as an important protective measure for lead workers, drinking a glass of milk between meals, say at 10 a.m. and 4 p.m., in order to diminish the chance that the lead they have swallowed be dissolved in the stomach.
Alcoholic Drink.—The influence of alcohol on industrial poisoning is important, although not so important as is generally supposed by employers, managers and foremen. I believe there is no form of industrial intoxication in industry, from lead to carbon disulphid, which I have not heard attributed to alcohol, no matter what the clinical picture might be. Even physicians often assure me that the lead, or mercury, or anilin, or naphtha poisoning, about which I am inquiring, never occurs in sober men, only in alcoholics; yet if they would copy the careful methods ‘used by 'Tanquerel des Planches (5), a century ago, they could easily convince themselves,
_as he did, that many men who lead sober, righteous and godly lives,
suffer as severely as the drunkards. (See page 14.)
Nevertheless Tanquerel admits the influence of alcohol on lead poisoning and points to the records of the Charité Hospital in Paris where the largest number of cases of plumbism came in on Tuesday and Wednesday, a fact which he attributes to the debauch of Sunday. Pieraccini(6) says that lead and alcohol make up a vicious circle, for alcohol favors plumbism and plumbism increases the craving for aleohol. It is certainly true that many lead workers believe that beer “cuts the lead and carries it off,’ because it washes away the disagreeable, sweetish taste in early plumbism better than any other drink.
Much more striking is the effect of alcohol on the palsy of mer-
6 INDUSTRIAL POISONS IN THE UNITED STATES ©
curlalism and the cerebral symptoms of nitroglycerim poisoning, and OL polsoliny Irom sulphuric ether, Irom anilin, uitrobenzene, winitrowiueue aud ower Coul tar compounds. this is treated im detall 1n the sections on these poisons.
Anemu, Wephritis, etc.—UVertaim constitutional defects are geu- erally regarded as rendering a person untt tor employment 1m poi- sonous trades. ‘Lhus damaged kidneys will make elimination or the poison more difficult, anemia will add to the danger ot benzene pol- soning, and ot plumobism, anilinism, etc., which involve loss ot red cells. ‘L'his is a neld which still waits tor thorough imvestigation, aud unt that 1s done we are dependeut on @ prior. reasonimg only.
Lnjluence of tcace.—t.xperienced toremen and employers ot iabor beneve that there 1s a diiterence between colored and wuite men with regard to thelr susceptibility to certain industrial poisons. the inegro is generally heid to be especially resistant to those poisous which attect the skin, causing various torms of trade eruptions, and also to those poisons which gain entrance through the skin. \ Lhus im the raking ot dye intermediates and coal tar dyes it is said to be desirable to employ Negroes in the preparation and handling of such substances as paranitranilin and dinitrochlorbenzene be- cause they are not subject to the distressing dermatoses from which white men suitter when they do work of this sort. 1 have also been told that Negroes can work with anilin, with dinitrobenzene, and with the nitrotoluenes with less danger of systemic poisoning than can white men. Some foremen even maintain that in dealing with these poisons, which enter through the skin, men of fair complexion will be found more susceptible than men of dark complexion.
Actual experience during the war proved that the skin of the Negro is not so sensitive to irritating chemicals as is the skin of white men. Marshall, Lynch, Smith, and Williams, of the Chemical Wartare Service, tested the susceptibility of white and of colored men to mustard gas. A certain degree of resistance was displayed by about 20 per cent to 40 per cent of the whites, but by 78 per cent of the colored. ‘l'wo per cent of the whites showed excessive sensitivity, but none of the Negroes. In a study of ‘INL poisoning in six nitrating and shell-loading plants, by the National Research Council, it was found that Negroes sutiered far less from TNT der- matitis than white men (1). .t was not, however, possible to prove that their susceptibility to systemic poisoning was slighter, although this was the opinion held by the men in charge of the two plants in which colored men were employed. In one of these, a shell- loading plant in Virginia, ‘le Linde found no case of TNT sickness among the Negroes. ‘Those who were working in the same depart- ments with white men sometimes showed, by the Webster reaction in the urine, that they had absorbed TNT, but the urinary changes
INDUSTRIAL POISONS IN THE UNITED STATES 7
were never as marked as in the case of the white men, nor did the colored men complain of any symptoms of poisoning.
On the other hand, Herman and Putnam, working in a nitration plant in Pennsylvania, found no difference in the susceptibility of the two races. In examining 37 white men and 13 Negroes, they found some cases of marked poisoning among the latter, indeed the most typical case of TNT poisoning that they saw was in a Negro. These observations were of more value than those made in shell- loading plants, because in the latter Negroes and whites were in only rare instances employed in the same department, while in the nitration plant they worked together. Besides this, the Negroes in the Virginia plant lived in their own cabins, the whites in com- pany barracks with the company canteen, and the Negroes were much more cleanly in their habits, more willing to take baths than were the mountain whites. In the Pennsylvania plant the two races lived and worked under the same conditions.
This disappearance of the apparent difference in enniee between the two races when they are placed under the same con- ditions was found by the French also in munition plants during the war. According to Roger G. Perkins (7), there were three races employed in producing and loading the French explosive mélinite, a mixture of picrie acid (trinitrophenol), and dinitro- phenol, the latter of which proved to be very poisonous. At first it seemed that the yellow race, the Annamites, were decidedly the most resistant, and the whites the least so, with the blacks occupying the middle place. Later on, however, the French concluded that the differences between the yellow race and the white could be accounted for on other grounds than that of racial susceptibility. The white men were more intemperate, more uncleanly in their habits, and less obedient to shop discipline than were the yellow men, and in addition the most expert medical supervision was given to the white men, resulting in a more careful diagnosis and the detection of earlier cases.
On the other hand, Negroes are held to be more susceptible to lead poisoning than white men. This is an opinion generally . held by lead men who employ both races. It has never been pos- sible to prove or disprove this theory by actual figures and it may be that it rests on the fact that Negroes are more likely to develop the brain form of plumbism, lead encephalopathy, than are white men. Edsall (8), found that there were three encephalopathies among six cases of plumbism in Negroes in the Episcopal Hospital in Philadelphia, a larger proportion than has ever been recorded among whites. I have had opportunity to study only two lead trades in which both colored and white men were employed, in making of white lead (9), and the smelting of lead (10). In both, the proportion of encephalopathies among the Negroes was strikingly
°8 INDUSTRIAL POISONS IN THE UNITED STATES |
high. There were nine cases of lead encephalopathy in the white lead industry during the sixteen months from January 1st, 1910, to April 30th, 1911. At that time only 15 per cent of the employees were Negroes, but four out of these nine cases of lead convulsions were in Negroes. In lead smelting during the year 1912, the only plants in which there were large numbers of cases of encephalopathy were the three in which the very dangerous Scotch hearths were in - use with their extensive dust collecting system, also fraught with unusual danger. In these smelters 875 white men had had 22 cases of encephalopathy, making a rate of 1.3 per hundred employees per year, and 110 Negroes had had 15 cases, or 6.8-per hundred. In order to make the comparison between the two races in a single plant, the records of white and colored men engaged in the three most dangerous departments, the Scotch hearths, the flues and bag house, and the sublimed white lead department, were compared, with the following result: among 84 white men there were 4 cases, or 4.7 per hundred; among 75 Negroes there were 15 cases, or 20 per hundred.
As for the difference between various white nationalities I have found no statement in the literature except one by Legge and Goadby (11), who tell of a lead factory in England in which the Italian workmen seemed to possess decidedly more resistance to lead than the English workmen, but they attribute this difference to habit not to nationality, for it seems to persist only so long as the Italians keep to their own diet and avoid excessive alcoholic drink.
Influence of Sex.—It is to the literature on lead poisoning that one must turn for material on the question of sex as a factor in industrial poisoning. British observers who have had much experi- ence with women exposed to lead in the white lead industry and also in the glazing, finishing, and decorating of pottery and tiles, hold that women not only succumb more quickly to lead but suffer more severely from its effects. Oliver (12), says, “So far as occupation exposure to lead is concerned my opinion is (1) that women are more susceptible than men; (2) that while female liability is greatest between the ages of 18 and 23 years, that of men is later; and (3) that while females rapidly break down in health under the influence of lead, men can work a longer time in the factory without suffering, their resistance apparently being greater.” He states that there were in 1897, 328 men employed in the white lead works in Neweastle-on-Tyne, and 571 women. During six months of that year 19 men were reported as having lead poisoning, a rate of 1 for every 17 employed, and 66 women, or 1 for every 8 or 9 employed, just double the rate. The report of the factory inspection depart- ment for 1910 shows that in the Staffordshire potteries there was twice as high a rate of plumbism among the women dippers as among the men dippers.
INDUSTRIAL POISONS IN THE UNITED STATES 9
In the United States women have never been employed in large numbers in the lead industries and very few really dangerous occu- pations are carried on by women, with the exception of litho transfer work, and even this has of late years lost much of its danger through the improvement of machinery. Women work at soldering machine parts and tin cans, and making molded lead articles; they also finish type by hand; but the only industry in the United States in which a study has been made of the comparative susceptibility of the two sexes to lead poisoning is in the glazing and decorating of pot- tery and tiles. An investigation of lead poisoning in potteries was made by me in Trenton, New Jersey, and in the East Liverpool and Zanesville regions of Ohio in 1912 (13), and it brought to light a high rate of lead poisoning among the women as vompared with the men, but a closer analysis threw doubt upon the part played by sex in this difference.
The pottery industry in the United States falls into two divisions: the so-called white-ware potteries which are organized in a strong trade union, and the art and utility potteries and tile works which are unorganized. The women are entirely unorganized in both fields. In the white-ware potteries, the contrast between the two sexes was striking. ‘There were only 39 cases of lead poisoning among 796 men, or 4.89 per hundred, and 29 cases among 156 women, or 19.3 per hundred, but the women had many handicaps aside from that of sex idiosyncrasy. They were unorganized, under- paid, poorly housed, poorly fed, subject to the worry and strain of supporting dependents on a low wage, while the men made high wages, were sure of their jobs, and lived comfortably. In the unor- ganized pottery fields, however, in the tile works and art and utility potteries, the men and women were in the same economic class, all making low wages with everything that that implies, and no appre- ciable difference was found there between the two sexes with regard to susceptibility to lead. Among 304 men there were 48 cases of lead poisoning, or 15.78 per hundred, and among 243 women there were 28 cases or 11.52 per hundred, a slightly lower rate, but then the women averaged a shorter period of employment than the men.
In discussing this question with the physicians of the Zanesville district I found that several of them had more men patients with lead poisoning, recognized as such, than women. The typical gastric form of plumbism seemed to be more frequent among the men, but
_ there were large numbers of women and young girls with less pro-
nounced and characteristic symptoms, such as obstinate constipation with profound anemia and sometimes amenorrhea. These were not usually listed as cases of plumbism, as they would be in British records, and this is probably the explanation for the discrepancy between the figures from American and British potteries. However, it is certainly true that economic conditions have an influence on
10 INDUSTRIAL POISONS IN THE UNITED STATES —
industrial lead poisoning and that when the two sexes are working under the same conditions and living in the same way there is no such great contrast between them as is found when the men are well paid and the women poorly paid.
In 1921 the United States Public Health Service oct: the report of an investigation made by Newman, McConnell, Spencer, and Phillips (14), of the occurrence of lead poisoning in the pottery trades of New Jersey, Pennsylvania, Ohio and West Vir- ginia, which was far more thorough than my earlier one. As a result of examinations made on 1436 men and 373 women they found that, although men are far more exposed to lead in this trade than women, there is more plumbism among the women than among the men. It is true that the rate of “positive and presump- tive” lead poisoning among the men was 14.2 per hundred, among the women, 11, but the low rate for women depends upon the shorter ex- posure of women and the slighter degree of exposure. When one esti- mates the length of exposure of the two sexes and compares the rates for men and women engaged in the same sort of work, the greater susceptibility of women is clear. ‘The average length of exposure of the “positive” male cases was 17 years, of the female cases, 9.3 years, while for the two ‘‘presumptive” groups the figures were 15.7 years and 6.3 years. “It should also be mentioned that in most plants the length of day for the female worker is from one-half hour to one hour shorter than that of the male worker. It would seem that the female reaches these stages of lead poisoning in about half the time required for the male to reach them.” Comparing the men and women who work side by side in the dipping rooms, it was found that 58 male ware-carriers had no positive cases of plumbism, while 62 women doing the same work had a rate of 4.8 per cent. Among 71 male dippers’ helpers the rate of plumbism was 8.4 per cent and among 149 female dippers’ helpers the rate of plumbism was 14.4 per cent.
The figures given by Prendergast (15), collected from the Staf- fordshire pottery district do not show the difference in rate between the two sexes, but the difference in the form which lead poisoning assumes. Women suffer more from lead convulsions and lead blind- ness, men suffer more from colic and palsy. His table is based on 640 cases:
Men Women GS ick hi va Wi ea aaa kes 77.6 per cent 69.8 per cent PUGS OIG > eines 68 visi b's Sees 57.0 per cent 30.0 per cent Lead Convulsions ......... 15.0 per cent 384.9 per cent Blindness (total) ......... 2.3 per cent 7.7 per cent Blindness (partial) ........ 3.5 per cent 10.2 per cent
This greater liability of women to lead convulsions and other forms of encephalopathy came to light in my study of the pottery
INDUSTRIAL POISONS IN THE UNITED STATES 11
industry in this country as well. In 1911 there were 1100 men employed in lead processes in the potteries which I investigated, and 87 cases of lead poisoning had occurred among them during that year, a rate of about 8 per cent. During the same year there were 57 cases among the 393 women employed, a rate of 14 per cent. The proportion of encephalopathy in the male cases was only 1 in 17, in the female cases 1 in 4.5.
In a study of the lead trades made by an Austrian Royal Com- mission in 1909, the question of women’s employment in lead work was taken up and the Commission urged strongly that it be forbidden by law. They based their opinion on their findings in the typo- graphical trades in which the women had a much higher rate of poisoning than the men. The rate among men type-setters was one in 35 employed, while among the women type-founders and founders’ helpers it was one in nine. These figures were brought forward at the International Association for Labor Legislation in 1910 and again in 1912, and the stand taken by the Austrians was vigorously seconded by the Italians under Carozzi, while it was combated by the British, who contended that the Austrian figures, applying as they did to quite different occupations, were not com- parable. Type-founding, done by women, involves much more - exposure to lead than does type-setting, done by men. The Italians were unable to present proof of the greater danger to women em- ployed in the printing trades in their country, and the British main- tained that it was not advisable to rule women out of this industry, to which their powers are well adapted, unless more definite proof of injury could be produced.
It was not possible during the war to draw any conclusions in this country as to sex susceptibility toward trinitrotoluene, for the employees in American plants were almost all men and when women were employed it was never in the most dangerous occupations. In England the mortality from TNT poisoning was greater among the women than among the men, 28.6 per cent of the reported cases, as against 20 per cent among the men, but the women were younger than the men, and Legge believes that their over-susceptibility is explained by their youth, not by their sex.
The record in the German munition plants, where men and women were employed in contact with dinitrobenzene, the most important of the explosives used by the Germans, showed quite unmistakably the greater susceptibility of women to this dangerous trade poison. The men in these plants were a selected group, incapacitated for military service by age or physical defect, or convalescing from wounds in battle. The women were an average working class group. The advantage, therefore, should have been on the side of the women who were not selected for their inferiority as were the men, yet there was more “DNB sickness” among them than among the men.
12 INDUSTRIAL POISONS IN THE UNITED STATES ©
In the Diisseldorf district, the proportion of cases of poisoning among the men in 1916 was 56.7 per hundred employed, among the women 66.0 per hundred. Then in 1918, when the food blockade was in full force and all were suffering from malnutrition, the cases among the men rose to 100.5 per hundred, but among the women the figure was 119 (2).
Another poison ertcountered in the making of munitions during the war, which seemed to cause more suffering in women than in men, was sulphuric ether, used in the manufacture of smokeless powder. It is evident that the British found the experiment of employing women in such work unsuccessful, for the report of the Chief Medical Inspector of Factories and Workshops for the year 1918 states that the women who were introduced into smoke- less powder work during the war suffered so much more severely from ether fumes than the men that it was necessary to put men in their place.
The effect of ether upon the girls and women employed in the American smokeless powder works will be described in detail in the section on sulphuric ether, It is sufficient to say here that a much larger proportion of the women than of the men felt the acute effects of the ether. While 48 of 80 women had one or more attacks of acute ether poisoning, only 9 of the 35 men experienced any acute ~ discomfort of this kind and 4 of these described it as so slight as not to interrupt their work at all. An examination of the blood made under the direction of Dr. George R. Minot showed decidedly more deviation from the normal in the girls than in the men.
Influence of Age-—The younger the patient the smaller the dose is the rule in medical practice with, of course, some striking excep- tions. Since we know of no such exceptions among the industrial poisons, it is safe to conclude that boys and girls are more susceptible to them than are grown people. This fact has long been accepted in European countries and legislation governing the dangerous trades forbids the employment of children or young persons in processes exposing them to poisons even when the danger is, to the American view, very slight. For instance, one of the least dangerous of — the lead trades is printing, yet in Germany there is a prohibition against allowing boys to blow out type cases; in Norway they may not sweep the floor of a printing shop; in Denmark they are for- bidden to work in the stereotype department; and the Austrian governmental report of 1909 advised that no young person be allowed to do any work which would bring him in contact with lead. The British experience with TNT in the early years of the war showed clearly the greater susceptibility of the young people. The general mortality from toxie jaundice was 25.9 per cent of the reported cases, but for persons under eighteen years of age the proportion was six deaths out of nine cases.
INDUSTRIAL POISONS IN THE UNITED STATES 13
We have very little data in the United States with regard to the greater susceptibility of young people to industrial poisons, partly because we have not, up to recently, employed many young people in such processes. Nevertheless, it is a subject which should be dealt with by legislation before the evil becomes greater. Our experience in shell-loading plants during the war showed that the younger men working with TNT suffered more from the effects than did the older men (1). In one very badly managed loading plant the custom was to discharge the men as soon as they showed signs of poisoning severe enough to lead the doctor to believe that the company might get into trouble. Of all the men who were discharged on account of sickness during one month, one-third were under 25 years of age, while the proportion of the entire force which belonged in that age group was only one-eighth. In the better man- aged factories, which were studied, the contrast between the older and younger men was not so striking but was clear. For instance, in one plant 48 cases of TNT poisoning fell into two groups, one consisting of 29 lads under 21 years, the other of 19 men over 30 years. The older men had averaged 49 days of work before they fell ill, the younger men only 1014 days. Similar results were obtained in a TNT nitration plant, the older men averaged 56 days’ exposure before they showed symptoms of poisoning, the younger men only 7 to 8 days. In these two plants the men under 25 years constituted less than 40 per cent of the force, but the fifteen cases of most rapid and serious poisoning were all in men under 25 years, most of them being 21 years old or less.
Benzene has recently come into increasing use as a solvent for rubber, shellac, cements, ete., and is now used by young men and girls as well as adults. There are no trustworthy data on the pro- portion of cases of benzene poisoning among the forces employed in any factory nor on the comparative severity of the poisoning m the young and in the mature, but it is perhaps significant that out of 34 severe cases of chronié poisoning in the literature 25 were in “young persons,” and out of 19 deaths, 15 were in this age group. Five were under 16 years of age. It seems obvious that benzene poisoning, with its tendency to hemorrhage, must be especially dan- gerous for menstruating girls and pregnant women. (See chapter on benzene. )
Among the occupations which should be forbidden to women and to lads under 18 years are the following, according to a recent. deci- sion of the International Labour Bureau: Production and use of solder with more than 10 per cent lead; melting lead or zine scrap on a large scale; mixing and pasting in making or repairing storage batteries; cleaning rooms in which lead smelting and refining, zine smelting, the preparation of oxids, and of lead colors and lead enamels and glazes, is carried on.
14 INDUSTRIAL POISONS IN THE UNITED STATES |
Individual. Susceptibility.—Idiosynerasy was understood by the Greeks to mean so peculiar a mixture of body fluids that the intro- duction of a drug would cause an abnormal reaction, either over- great or over-slight. Not only might the reaction to a drug be abnormally marked but a reagent which caused no injury to a normal person might set up symptoms in those with an idiosynerasy, and this idiosyncrasy was held to be inborn, often hereditary. We no longer talk of a peculiar mixture of body fluids, but we are no nearer than the Greeks to an explanation of the familiar phenomenon of one person reacting to rag-weed pollen, another developing hives after eating strawberries, another asthma because of the proximity of a horse. Nor can we explain why there is such a difference in the susceptibility of different individuals to the same industrial poison. All we know is that two men will be working at the lead pot, the one will be taken and the other left; two women will be spreading benzene cement, the one will be taken and the other left.
Tanquerel des Planches emphasized the great variation in suscep- tibility to lead that he had observed in different individuals. He says that “temperament does not count. The sanguine, the nervous, the lymphatic, are about equally susceptible.” Among his 1217 cases of plumbism, 424 were originally strong and vigorous; 584 were of medium strength; and only 208 were of feeble constitution. Aleohol and want of cleanliness have something to do with it, but “eases are not rare where persons of regular and sober lives have worked only a few days or months when they were attacked with colic.”
It is easy to collect instances of over-susceptibility to industrial poisons and I have included many in the case histories in the follow- ing chapters. Lead, arsenic, methyl alcohol, benzene, all these exhibit marked variations in their action on different individuals.. The men forming the crew of a submarine are all exposed to exactly the same concentration of hydrogen arsenid fumes for exactly the same length of time, their reactions to the poison cover a wide range. A construction gang in a steel mill is caught by escaping carbon monoxid gas, some die, others are only moderately gassed. Four men are imprisoned for a few minutes in a room full of ammonia fumes, one dies in 15 minutes, another after two hours, the third lives till the next day, the fourth recovers.
In the lead trades a great variation in susceptibility is always noted. In the early days, 1911, I visited a very dusty white lead works, and the man who was my guide told me he had worked there ever since he was twelve years old, for 32 years, and had never been poisoned, although at times he had been unable to see across the room for the thick lead dust. Yet in this same plant another man sickened at the end of two weeks and died of acute plumbism at the end of less than six months. Among 186 sanitary ware enamelers,
INDUSTRIAL POISONS IN THE UNITED STATES 15
equally exposed to lead enamel dust, the majority averaged over five years before severe plumbism developed, but 21 succumbed after less than six months. Among 167 smelter workers who had plumbism, were 18 who came down with lead poisoning in less than three weeks, the rest averaged more than three months. I have the record of a white lead worker in a dusty plant who went to the hospital with acute lead poisoning after three days’ work only, and of a bath-tub enameler who came down with colic after four days. Others react with unusual severity, as for instance a vigorous young Slav who had never been sick in his life before and who was employed in work not considered particularly hazardous, pouring lead glaze over roof tiles. After five months his appetite was gone, he was losing weight and strength, at the end of two months more he was seized with a sudden agonizing colic, fainted and when he recovered consciousness, passed into a violent delirium during which he was evidently suffering severely. This was followed by two weeks of mental confusion and impaired vision and when I saw him three months later he was still pale, nervous and weak and not yet able to go back to work. Dr. Stybr, of Pittsburgh, reported to me a case which he had seen in 1910, in an enameler of bath-tubs. He was suffering from acute plumbism with colic when he came to Dr. Stybr, and was under treatment ten weeks before he could go back to work in May. In September Dr. Stybr saw him again, and this time he had complete double wrist drop, partial paralysis of the tongue and of the muscles of the throat and larynx, and his mentality was distinctly clouded. He died the following February. It is safe to say that there is no feature of industrial poisoning so troublesome to the physician as this difference in susceptibility. If only it were possible to determine once for all the minimum dose of a poison which could possibly give rise to symptoms, the whole problem of prevention would be so much simpler. Unfortu- nately the industrial physician must face the fact that in any large group of men or women there will be some individuals whom he cannot possibly recognize when he makes his initial examination, who do not betray themselves in any way, but who sooner or later are destined to fall victims to a quantity of poisonous dust or vapor which has no effect on the rest. It will be very hard for him to get his employer to see this, for the practical layman believes that what is dangerous for one man must be dangerous for all. He knows that a spurt of molten metal will burn any man it strikes; a falling scaffold, a current of electricity, a bursting fly wheel, these do not injure one and spare another. The damage is in direct proportion to the exposure. Why then, he argues, should one man get lead poisoning from work over a melting pot when twenty men in the same room do not show the slightest sign of ill-health? Yet this same employer recognizes the everyday fact that in any epidemic of any
16 INDUSTRIAL POISONS IN THE UNITED STATES
kind a large proportion of the population is not taken sick. Even at the height of the great influenza visitation the victims were always in the minority. If a village with 500 inhabitants has its water supply infected with typhoid bacilli, there will not be 500 cases of typhoid fever, there may not be 50. But if there are no more than five, the. infected water is responsible and not some innate depravity in the five individuals.
Even animals show a great variation in their susceptibility to poi- sons, yet they cannot be accused of alcoholism, or dyspepsia from eating pie, or late hours and excessive dancing, or any of the other sins against personal hygiene so comforting to the worried employer. Stieglitz (16), who worked with rabbits and guinea-pigs, trying to produce experimental plumbism by spraying a solution of lead acetate into the cage, found that not only did the animals vary with regard to the severity of the poisoning but also with regard to the localization, for in some the kidneys suffered most, in others the blood vessels, and in others the central nervous system. The same sort of evidence is given repeatedly by Lehmann and his colleagues, to whom is due so much of our knowledge concerning the action of toxic industrial gases, and indeed it may be said to be the universal experience of animal experimenters.
It is important, however, to be sure that a rapidly developing case of industrial poisoning is really due to idiosynerasy and not to an accident or a neglect resulting in an excessive exposure to the poison. A few years ago the investigation of any lead industry in the United States seemed to bring to light a large number of over-susceptible men who had developed serious poisoning after only a short expos- ure, but a closer study always showed that, while some of them might have sickened quickly because of an idiosynerasy to lead, the larger number had to be attributed to an excessive exposure to lead dust or fumes. For instance, an article was published in 1898 by Hobbs (17), of Omaha, telling of his experience with the employees of a very dusty white lead plant. He saw 26 cases develop after an exposure of less than six months, some of no more than two weeks. Some twelve years later when I visited this same plant, I found that there was still a large number of cases of rapidly developing plumb- ism. One-half of 120 recent cases of acute plumbism had developed after less than two months’ exposure, and 68 per cent after less than six months. This proportion is far too large to be explained on the ground of individual susceptibility; the really over-susceptible were probably the men, some 6.6 per cent of the whole number, who became poisoned in less than two weeks’ time, one of them after only three days.
In the same way one must distinguish between the excessive expos- ure and individual susceptibility in the men of another dangerous lead trade—smelting and refining in neglected and poorly con-
INDUSTRIAL POISONS IN THE UNITED STATES 17
structed plants. In 1912 one very badly managed western smelter had 167 cases of fairly severe plumbism, and no less than 72 per cent of these men had succumbed after an exposure of less than six months. Here the over-susceptible men may have been the 37 who were poisoned after less than eight weeks’ work. Hall’s (18), report of lead poisoning in the American Smelting and Refining Company’s plant at Aguas Calientes, Mexico, shows that excessively bad conditions in a lead smelter can bring about even more rapid poisoning than this, for the flue dust men in that plant sometimes developed acute symptoms after 72 hours’ work and were usually incapacitated at the end of eight to ten days.
Hirt (19) tells us that from 20 to 30 per cent of all lead workers are not susceptible to lead and that of the remaining 70 to 80 per cent, something over one-half become poisoned very quickly, the others more slowly. The only accurate figures I was able to obtain on this point in an American lead trade showed a smaller propor- tion of non-susceptibles than Hirt’s. There were two very dangerous white lead factories which I visited in 1911 and in which every man was given a medical examination at least once in a fortnight. The records showed that 35 per cent of all of the men in one factory had plumbism, and 28 per cent of all in the other factory. However, when I omitted the newer employees and included only those who had been employed as long as one year, I found that the rates were 52 per cent and 40 per cent. Only 10 per cent in one factory and 12 per cent in the other had been able to resist the effects of lead for as long as eight years.
BIBLioGRAPHY
(1) Hamizton, A. “Trinitrotoluene as an Industrial Poison,” Jour. Indust. Hyg., 1920-21, 2, 102.
(2) See Abstr. “Jahresber. d. gewerbl. Aufsichtsbeamten vy. Bergbehérden,” 1914-18, in J. Ind. Hyg., 1920-21, 2, 98.
(3) Hamitton, A. Industrial Poisons Used or Produced in the Manu- pk ‘of Explosives, Bull. 219, U. S. Bureau of Labor Statistics, 191
(4) Caruson, A. J., and Wortret, A. Hygiene of the Painters’ Trade, Bull. 120, 0, U. ’s. Bureau of Labor Statistics, 1913; also J. A. M. A., 1913, 59, 181.
(5) TanquerEL pes Puiancues. Lead Diseases, a Treatise, from the French of L. Tanquerel des Planches, trans. by Samuel L. Dana, Lowell, 1850.
(6) Preracctnt, G. Patologia del Lavoro. Milan, 1902, 215.
(7) Perkins, R. G. Pub. Health Rept., Washington, 1919, 34, 2335.
(8) Epsatt, D. L., and Gwyn, N. B. Modern Med., Osler & McCrae, 1914, 2, 358.
(9) Hannut0w, A. “The White Lead and the Red Lead Industry,” Bull.
5, U. S. Bur. of Labor Statistics, 1911. (10) Me ance A. “Lead Poisoning in the Smelting and Refining of Lead,” Bull. 141, U. S. Bureau of Labor Statistics, 1914.
18 INDUSTRIAL POISONS IN THE UNITED STATES
(11) Lecce, G. M., and Goapsy, K. Lead Poisoning and Lead Absorption, London, 1912, p. 911.
(12) Ottver, G. Dangerous Trades, London, 1912, p. 297.
(18) Hamitton, A. “Lead Poisoning in Potteries and Tile Works,” Bull. 104, U. S. Bureau of Labor Statistics, 1912.
(14) Newman, B. J., McConnetit, Wm. J., Spencer, O. M., and Puruirs, F. M. Public Health Bull.-No. 116, May, 1921.
(15). Prenvercast, W. D. Brit. M. J., 1910, I, 1164.
(16) Srirecuitz. “Eine exper. Untersuchung ii. Bleivergift.” Arch f. Psychiat., 1892, 24, 1.
(17) Hosss. N.Y. Med. J., 1898, 68, 322.
(18) Haut, H. C. Texas State J. Med., Ft. Worth, 1914, 10, 308.
(19) Hirt, L. Die Krankheiten der Arbeiter. Breslau, 1871, vol. 2, 36.
CHAPTER 2 LEAD PATHOLOGY
Leap came into use very early in the history of civilization and its poisonous effects were soon discovered. Greek, Latin and Arabian physicians knew that lead would cause colic if swallowed. Dioscorides, in the first or second century after Christ, accurately described not only lead colic but paralysis, following the swallowing of lead, and also knew that breathing lead fumes would cause the same disorder. He spoke of the mechanical devices used in his day by workmen to protect themselves from lead fumes. His “molybdania” is supposed to have been litharge. Pliny used the word minium in its present meaning of red lead, and white lead was known to the famous Arabian alchemist, Geber.
It was the widespread use of lead as material for cooking vessels and other household articles that caused the most notorious outbreaks of lead poisoning, except in France, where it was the custom to promote acid fermentation in wine by adding lead to it. Since Poitou was the region in which this custom prevailed the name of “colic of Poitou” was given to lead colic. Stockhausen in 1656 pub- lished at Goslar a treatise declaring that Poitou colic was caused by lead, and he drew an accurate picture of clinical plumbism. The principal source reported in early days in England was _lead- contaminated cider, and in Spain there was much poisoning from the use of lead to line cooking vessels. The best work on the subject of industrial plumbism was done in France in the early part of the nineteenth century, culminating in and overshadowed by the epoch- making treatise of Tanquerel des Planches, (1) “the Columbus of lead poisoning.” Tanquerel had abundant clinical material; for there were received at the Hospital of La Charité in Paris between 1831 and 1839 no less than 1217 cases of lead colic. White lead work was responsible for 406 of the cases; painting for 382; red lead and massicot making, for 75; color grinding, for 68; potteries, for 61; lapidaries, for 35; refining, for 25; German glazed card making, for 11; making lead salts, for 10; and fifteen other trades had less than 10 each. Tanquerel saw also arthralgia in 755 cases, paralyses in 127, and encephalopathy in 72. Tanquerel’s clinical observations were very accurate, and not much of importance has been added to them. He also noted what has escaped many industrial physicians since his day, that severe poisoning could always be traced to lead
19
| 20 INDUSTRIAL POISONS IN THE UNITED STATES
vapors or emanations. Only relatively mild and slow poisoning fol- lowed contact with solid lead or lead paint. He even tried to settle the question of lead absorption through the unbroken skin by experi- ments with two dogs and a rabbit, but he did not succeed in poisoning them, and he was sceptical as to the possibility of lead poisoning ever occurring in that way.
The pathological anatomy of lead encephalopathy interested Tanquerel, and his contributions to this field are valuable. He also confirmed Bright’s observations on the connection between chronic plumbism and contracted kidney.
After Tanquerel, a vast amount of clinical data on industrial plumbism was collected in Germany, England and France, and dur- ing the latter half of the last century the pathological anatomy was the subject of much study, especially in Germany. ‘The field which still awaits a thorough exploration is the pathological physiology and chemistry of lead poisoning, the exact mode of absorption of lead, the changes it undergoes in the body, its mode of action, its storing and excretion and the changes it produces in the tissues. Much work has already been done in this field, but with results which are more or less contradictory or unconvincing.
Vascular System.—In a work of this kind only a brief résumé can be given of what has been done in the field of research into the pathology of plumbism, 7.e., the changes in body fluids and tissues which underly the clinical symptoms. While no organ or tissue remains quite unaffected by the presence of lead, if this be prolonged, the action of lead is generally believed to be exerted primarily, not on the organs but on the vascular system.
According to most authorities the underlying pathology of chronic lead poisoning is a structural change in the blood vessels. Ever since the researches of Maier (2), and his pupils in the early eighties it has been held that lead circulating in the blood sets up changes in the walls of the smaller vessels, consisting essentially in an end- arteritis and a periarteritis, and that these produce a loss of elasticity of the vessel wall, the formation of multiple aneurysmal dilatations, thrombosis, or rupture with hemorrhage, and as a consequence, slow starvation of the tissues whose blood supply is progressively dimin- ished. The well-known lesions of chronic plumbism, contracted kidney, atrophy of the optic disc, apoplexy, and progressive paralysis of the insane, are attributed to structural changes in the vessel walls.
Not only the lesions of chronic plumbism, but the symptoms of the acute forms, lead colic and encephalopathy and blindness, tran- sient or lasting, are traced to the action of lead on the vessels, to the production of a vaso-constriction resulting in temporary ischemia, with passive congestion and edema. Such a vaso- constrictor spasm is seen as the cause of the dry, anemic brain found in some cases of encephalopathy (Klschnig (3)), or the “patchy —
INDUSTRIAL POISONS IN THE UNITED STATES 21
edema” of Oliver (4), or retinal ischemia, edema or hemorrhage. Cases of fatal encephalopathy with no anatomical lesions (West- phal (5)), of transient blindness with no structural change in the retina (Elschnig (3)), are also explained thus.
Kussmaul and Maier (6) published in 1882 their much quoted findings in a case of chronic plumbism. The man affected had been a painter for many years, and had several acute attacks of plumbism, in one of which he died. They found in the stomach endarteritis, thickened mucosa, and atrophy of the glands, with a marked prolifera- tion of the connective tissue. These changes were still more marked in the intestine where the walls of the vessels, the small arteries in particular, showed thickening of the coat and narrowing of the lumen. Around the arteries of the brain they found a slight periar- teritis. Later Maier’s pupils found pathological changes, including multiple aneurisms, in the vessels of the central nervous system (Dressler), of the kidneys (Hoffa), and of the intestines (Gese- nius).
Jores (7), endeavored to confirm the findings experimentally, but was quite unable to produce in rabbits any chronic lesion of the blood vessels, even after prolonged administration by mouth of lead acetate (from 2 months and 9 days up to 14 months and 20 days). None of the changes in the vaseular system described by Maier and his pupils appeared, no fatty degenerations in fresh or in hardened specimens, no endarteritis or aneurysm or rupture, but only a uni- form dilatation, very marked in the small vessels of the mesentery and stomach. These dilatations, Jores thought, probably encouraged the formation of thrombi from the products of the destruction of red blood corpuscles.
As to the exact nature of the vascular change set up by the pres- ence of lead in the blood there was much controversy. The earlier pathologists, Rosenstein (8), Hitzig (9), Henle (10), believed that the circulatory disturbances set up by lead were caused by a direct irritation of the non-striated muscles of the vessel wall, while French experimenters hold that the etfect on the vessels is secondary, and that the primary action of lead is exerted on the adrenal cortex (Gouget (11), Bernard, and Bigart (12)), causing hypertrophy and histological changes. Siccardi (13), however, succeeded in produc- ing vaso-constriction in the veins and arteries of large mammals by bathing them in lead solution. He could provoke a progressive intense constriction proportional, within certain limits, to the dose employed, and never preceded or followed by a dilatation. This constriction could be overcome by lavage followed by atropin, another proof that the action is on the muscles of the median coat. With the aid of sulphuretted hydrogen, Siccardi claims to have demon- strated lead in this coat. He produced the same constriction in vessels treated in situ, more marked in the vessels of kidney and
22 INDUSTRIAL POISONS IN THE UNITED STATES
liver than in the musculo-cutaneous. In spite of this vaso-constric- tion, Siccardi found the action of lead predominantly depressant on the blood pressure except for a transient rise after a minimal dose, and this he explained by its action on the isolated heart; for in minimal doses lead lowers the functional activity of the heart, affect- ing tonus, energy and rhythm, and leading to arrest in diastole. Since this effect is neutralized by adrenin and not by atropin, Siccardi concludes that in the heart the action of lead is exerted directly on the heart muscle.
The changes in the vascular system in chronic poisoning are such as follow repeated, excessive vacillations in the blood pressure (Thoma (14)). The proliferative endarteritis is probably repara- tive and compensatory to the damage done to the muscular coat, but, as usually happens in such repair processes, the changes may be out of all proportion to the damage in the media. The sub- endothelial connective tissue proliferates and then undergoes fatty, hyalin, and calcareous degeneration, resulting sometimes in com- plete occlusion of the vessel. A very striking case of obliterative endarteritis was described recently by Timme (15), in a painter who suffered from.senile gangrene of the feet to a degree necessitat- ing amputation. The vessels in the feet were found to be occluded and lead was isolated from the atrophied muscles.
Brain.—The study of the anatomical basis of the cerebral form of plumbism was eagerly pursued during the latter half of the last century, and it was in this field that the greatest contributions were made to the understanding of the mode of action of lead. We are indebted to Westphal not only for brilliant work on the pathology of cerebral plumbism, but also for a thorough review of the work which had been. published prior to 1888. Briefly it may be abstracted as follows: Kussmaul and Maier were the first to make a microscopic examination of the brain (all of Tanquerel’s observa- tions, largely negative, were of the gross anatomy only) with the result mentioned above,—the discovery of periarteritis of the cere bral vessels and a slight narrowing of the lumen of the smaller vessels in the cortex. Von Monakow’s (16) study, which is widely quoted, was made on a case of progressive general paralysis, and he found changes typical of progressive paralysis of the insane, namely, a marked atrophy, especially of the frontal and parietal regions and of the brain stem. Microscopically, there was in the atrophied areas an increase of the adventitia of the vessels, with cell proliferation and infiltration, fat droplets and pigment. There was also atrophy of the nuclei of the hypoglossus and the trigeminus. Seiffert (17) found atheromatous plaques in the basilar arteries, with thickening of the pia and enlargement of the lateral ventricles. In Oellers’s (18) case there was an obliterative endarteritis in the vessels of the optic nerve, the retina, and the choroid, and Oppenheim (19) found a
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INDUSTRIAL POISONS IN THE UNITED STATES 28
fresh hemorrhage in the brain and an apoplectic cyst. His case was one of coma, delirium, and left-sided hemiplegia.
Westphal’s theory is that there are at least four ways in which lead may exert its effect on the brain. First, there is a direct action which is shown through general cerebral symptoms or through focal changes. He places here those peculiar neuroses which are accom- panied by hemianesthesia and psychic disorders, and which may at the same time show focal anatomic lesions in the cerebral nerves, most commonly the optic. Second, comes the effect of lead on the blood vessels of the brain, an arteritis with its sequele, hemor- rhage and encephalomalacia. Third, is the effect of lead on the kidneys, which may cause uremic symptoms, and fourth there is a combination of these. ‘The next comprehensive review of the path- ology of cerebral plumbism is Quensel’s (20), published in 1902.
‘He finds in the literature descriptions of six cases of cerebral plumb-
ism without any lesion beyond edema or anemia; five with vascular lesions or hemorrhage; and eight with changes characteristic of dementia paralytica, 7.e., atrophy of the cortex, chronic inflammation of the meninges with adhesions, hydrocephalus internus and externus, ependymitis, ete. The occurrence of fatal encephalopathy without demonstrable lesions in the brain is noted also by Oliver who, on the basis of his own observations, says that the usual finding is marked pallor and dryness of the brain, which is hard and inelastic, with flattened surface, or perhaps with edema.
Such an encephalopathy and amaurosis with no anatomical find- ings is to be attributed either to high arterial tension or to toxemia. The former explanation is favored by most observers. Thus Elschnig (3) says that he has seen spasmodic ischemia of the retina in a case of transient lead blindness, and endarteritis, with atrophy of the disk, in a case of permanent blindness. He believes that these two illustrate two stages of the same process; for as
‘Thoma has shown, intense variations in the blood pressure result
in thickening the vessel walls. Mosny (21) and his pupils reported a ease of transient blindness, lasting twenty-four hours, due prob- ably to arterial spasm localized in the occipital region. There was homonymous hemianopsia, and it was accompanied by marked mental torpor and weakness which cleared up as the blindness passed over. The pupillary reactions were normal and there were no changes visible in the eye grounds.
A case of this kind came to my notice in Cincinnati and was seen at autopsy by Dr. Paul Woolley. The patient was a young Negro who developed acute encephalopathy while employed in a white lead factory. After showing vague prodromal symptoms he fell uncon- scious in the street and died without recovering consciousness. Dr. Woolley reported that the brain was anemic and very dry, but other- wise normal with no evidence of arteriosclerosis in any of the arteries
24 INDUSTRIAL POISONS IN THE UNITED STATES
of the gray matter. There have also been cases of encephalopathy apparently uremic in origin, yet at autopsy no granular kidney was found. Here, according to Miller (22), the underlying pathology may be a vascular spasm resulting in deficient renal function. He quotes Hughes and Carter as having shown that the uremic symp- tom complex may occur without any kidney lesion. Ménétrier (23), who saw a case of saturnine encephalopathy developing during a colic, in a young pewter polisher, believed that it was a cerebral uremia, caused primarily by high arterial tension, in spite of the absence of changes in the kidneys; for the most striking symptom was the high arterial pressure, especially just before the convulsion came on. Since no atheroma was found at autopsy or any change in the adrenals, he believed that the lead had acted directly on the vasomotor nerves. Traube’s (24) theory was that lead encephal- opathy is always uremic, but Tanquerel insisted that the absence of nephritis is one of the characteristics of true lead encephalopathy.
The presence of lead in the brain has led men to think of a possible toxic action directly on the brain cells. Quensel found 19 cases in the literature in which lead was isolated from the brain, the earliest being Empis’ and Robinet’s in 1852. Jolly (28), Oppenheim, Herr- mann (29), and Trimborn (30) hold to this view, as does Westphal, so far as the causation of neuroses and hemianesthesias are concerned.
Wynter Blyth (25) found in the brain of a man dying of lead poisoning with pronounced cerebral symptoms 105.77 mg. of lead, estimated as sulphate, and in another with similar symptoms, 117 mg. Goadby (26) examined the brain of an eighteen-year-old girl who died of lead encephalopathy after nine months’ employment in mak- ing litho-transfer papers. All the vessels were engorged and there were capillary hemorrhages. From 250 g. of brain tissue 46.6 mg. of lead was recovered. Oliver also has had lead isolated from the brain after death from lead encephalopathy but he insists that in other cases quite as typical as those in which lead is found, the search for it may be fruitless. Quensel holds that such a negative result is not conclusive; for experience shows that lead may be un- equally distributed through the various parts of the brain, and may be lacking in just the part selected for analysis.
A toxic action of lead on the ganglion cells of brain and cord is said to occur in experimental and in clinical lead poisoning. Nissl (81) claims to have produced in rabbits with subacute plumbism lasting ten days, changes in the cells of the anterior horns, disap- pearance of the Nissl bodies, stippling of the protoplasm, shrinking and distortion of the nucleus, which turns into a pale, homogeneous, shapeless mass. He found later similar changes in Purkinje cells. Ceni (27) found in a man who died in coma, atrophy, edema, and anemia of the cerebrum, and degenerative changes in the ganglion cells (Marchi’s and Golgi’s methods), especially in the large pyrami-
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INDUSTRIAL POISONS IN THE UNITED STATES 25
dal cells of the deeper layers of the cortex in the neighborhood of the vessels, the walls of which were for the most part not thickened, but full of fat granules. Spiller (42) quotes observations made by McCarthy on dogs poisoned with lead acetate. There were degenera- tive changes in the cortex, most marked around the gyrus cruciatus, which corresponds to the motor area of the cortex in man. The nerve cells were degenerated, the capillaries of the cortex increased, their walls thickened, surrounded by accumulations of cells, and there were small hemorrhages. into the cortex.
G. B. Hassin (32), in a recent article, describes the difference between epidemic encephalitis, which is of infectious or igin and re- sembles in its pathology paralytic dementia, and the toxic group, represented by lead. The first is an infiltrative encephalitis, charac- terized by excessive, widespread, perivascular and sometimes paren- chymatous infiltrations, the pia-arachnoid changes being quite mild. Lead encephalitis, on the other hand, is a productive process, char-: acterized by proliferative phenomena in the mesodermic tissues (blood vessels, capillaries, and the pia-arachnoid). ‘The study of the pia- arachnoid is of great importance; for these structures may exhibit changes, even when the brain tissues proper appear normal.*
Spinal Cord and Peripheral Nerves.—The study of the pathology of lead palsy has revealed degenerative changes in the peripheral nerves and in groups of muscles supplied by them, in the anterior root ganglia and in the motor cells of the anterior horns of the spinal cord. Which of these lesions is primary, and whether lead palsy is a toxic neuritis, or the result of toxic injury to the motor-trophice cells of the anterior horns, 7.e., a poliomyelitis anterior, is a question concerning which there was active controversy for many years.
The earlier pathologists held to the latter theory, the central origin of lead palsy. Thus Vulpian (34) claimed to have produced in dogs a saturnine chronic poliomyelitis anterior with progressive spinal paralysis. Even tabes was in some cases attributed to lead. Red- lich (35) of Vienna found among 100 cases of tabes four in which lead was a possible etiological factor, and in one of them he thought syphilis could be definitely excluded. Other observations of this kind followed the publication of his article, but as all were made before the introduction of the Wassermann test they were later re- jected. In 1892, Eichhorst (36) came out for the primary neuritis theory, on the basis of a case in which the degenerative changes were confined to the radial nerve, with muscles and spinal cord intact. Remak (37), who at first had held lead palsy to be caused
*An interesting experiment was made by Camus (33) who injected ex- tremely small doses of lead chlorid (one or two c.c. of a 2-1000 solution) into. the cerebrospinal canal of dogs, between the atlas and the occipital bone. For two days nothing happened, but then came increasing excitability, hallucinations,
convulsions, and death. No such result followed similar injections into the white matter of the brain.
26 INDUSTRIAL POISONS IN THE UNITED STATES
by a chronic cervical poliomyelitis anterior, because of the peculiar distribution, later went over to the theory of the peripheral character of the palsy, as did also Oppenheim. Yet as recently as 1900 Gordon (88), who saw a case of lead palsy of the muscles supplied by the ulnar nerve, those forming the thenar and hypothenar emi- nences, followed by atrophy of the interosseous muscles, held that it was not a primary degeneration of the ulnar nerve but a progressive muscular atrophy of spinal type.
Gombault and Charcot (39) called lead palsy a special form of peripheral neuritis, segmentary and periaxial, the axis cylinder escaping damage and normal segments of nerve trunk being found above and below the damaged ones. Therefore, in contrast to Waller- ian degeneration with involvement of the axis cylinder, the neuritis of plumbism is curable. Mme. Déjérine-Klumpke (40), who in 1889 described progressive muscular atrophy in plumbism, held that it is due to a combined lesion of the anterior roots, the cells of the anterior _ horns, and of the peripheral nerves.
Stieglitz (41) tried to clear up the question as to the peripheral or central origin of lead palsy by experiments on ten rabbits and thirteen guinea-pigs which he poisoned by means of a spray of lead acetate. He did produce palsy in four and cerebral symptoms in eleven, but there were changes not only in the anterior horn cells but in nerves and muscles as well. He also found the posterior roots more or less degenerated and he insists that in man there must be damage to the sensory fibers or how explain the occurrence of arthralgia, which is so common that Tanquerel found it in thirty-five per cent of all cases ?
Kobert’s (42) opinion is that in most cases of lead palsy there is a polyneuritis saturnina, a primary disease of the peripheral motor nerves set up by lead and inducing a degenerative atrophy of nerve fibers which is followed by degeneration and atrophy of the muscles supplied by them. He admits, however, that in some cases, such as Vulpian’s, von Monakow’s, and Oppenheim’s, there does seem to have been a primary inflammation involving the anterior horn cells. He gives Prévost and Binet credit for first producing experimentally a peripheral motor neuritis through the administration of lead.
Spiller (43) examined the brain and cord of a man of 48 years who died of lead encephalopathy, with palsy of the upper extremities and weakness of the lower. He found in the cord no degeneration of the white matter, but intense degeneration of the anterior horn cells, of the cells of the cervical and lumbar regions. The roots were little altered, but there was very marked degeneration of the median nerves (Marchi and Weigert stains) and an increase of nuclei be- tween muscle fibers, 7.¢., an interstitial myositis. It was quite impos- sible to decide in what order these changes had occurred.
At a joint meeting of the Philadelphia and New York Neurologi-
INDUSTRIAL POISONS IN THE UNITED STATES 27
cal Societies, December 18, 1909, Mitchell (44) presented a case of typical amyotrophic lateral sclerosis with bulbar symptoms in a painter 53 years old, with no evidence of lead in his system at that time. There was no change: in sensibility. He died, and Cadwal- lader (45) made the autopsy. The patient had had many attacks of colic, palsy of the hands, difficulty in walking, indistinct speech, difficult swallowing, marked atrophy of all four limbs, muscular pains, and increased reflexes. Microscopically, there was pronounced disease of the anterior horn cells and degeneration of the lateral columns. In the cells the change was atrophic with the perinuclear chromatolysis so often found in primary cord disease; but the severity of the disease in the anterior horns did not bear any definite rela- tion to the intensity of degeneration in the lateral columns, and it was not possible to determine which was primarily affected.
C. A. Herter and Ira Van Gieson (46) reported before the New York Neurological Society in 1895 the history of a case of lead paralysis with the histological changes in the nervous system and the distribution of lead in the body. The man, who was 26 years old and who had been a painter for several years, was poorly nourished and undersized. He was first admitted to the city hospital in Feb- ruary, 1894, with double wrist drop and severe colic. On November 23d he was again admitted, this time with nausea and colic, weakness in the arms and legs, a marked lead line, and atheromatous arteries (moderate alcohol, no syphilis). There was complete loss of power in wrist and finger extensors on both sides and little power in flexors; atrophy of all the muscles below the elbow, especially the interossei ; slight ankle drop; feeble knee jerks. On December 7th he became drowsy and then fell into a muttering delirium with pin-point pupils, eyes prominent, respiration stertorous, pulse feeble, skin clammy. The urine contained casts, epithelial and granular, and albumin, and was low in urea while the urea content of the blood was two to three times the normal. The man died on December 12th. Van Gieson examined the nerves (in osmic acid) and found the follow- ing: in the ulnar nerve, about one fiber in ten moderately degen- erated; in the external peroneal, one in four; in the sciatic, one in ten; in the left external cutaneous, three in ten; in the right radial, one in twenty; in the left plantar, one in twelve. In the spinal cord few cells were destroyed, but in sections stained with anilin dyes degenerative changes were revealed in about one-third of the gang- lion cells, such as vacuoles, and breaking up of chromophilous gran- ules. Lead was found in the blood, in the central nervous system and organs, the spleen and kidneys containing most, the liver and spinal cord following. |
Laslett and Warrington (47) made a careful study of the spinal cord and of certain nerves and muscles of a young painter who died after suffering for some time from double wrist drop and extensive
28 INDUSTRIAL POISONS IN THE UNITED STATES
muscular atrophy. They found marked atrophy of the posterior interosseous nerve, with quite half of the fibers gone; less marked atrophy of the ulnar; and distinct atrophy of the anterior spinal roots of sixth, seventh and eighth dorsal segments of the cord; while _ the posterior roots were normal. ‘There was a marked atrophy of the extensor muscles, affecting over 90 per cent of the muscle fibers, which, however, retained their cross striations. Connective tissue was greatly increased. The interossei were less altered. ‘Muscle spindles and their nerves, derived from the posterior roots, were normal.” No change was seen in Marchi and in Weigert prepara- tions of the cord, but protoplasmic stains brought out alterations in the anterior horn cells, such as eccentric, shrunken nuclei, disinte- gration and dispersion of chromatin bodies, and even chromatolysis. They hold that such changes are secondary to the atrophy of the axones of the cells (the réaction a distance of Marinesco), in this ease chiefly affecting the cells of the sixth, seventh, and eighth segments, from which the axones of the interosseous nerves are derived.*
Kidneys.—The study of the kidney of chronic plumbism has pro- duced much evidence in favor of the view that plumbism is essentially a disturbance of the vascular system, functional in the acute, struc- tural in the chronic. As early as 1827 Bright (48) noted the con- nection between plumbism and albuminuria, Tanquerel mentioned it in 1839, and in 1868 Ollivier (49) confirmed their observations on human beings by producing changes in the kidneys in animals and demonstrating lead in the urine.t Wagner (50), in 1882, described saturnine nephritis as a special variety of contracted kidney, fifteen of his 150 cases being traceable to lead. Four of the fifteen had also arthritis urica. :
According to Striimpell (52) the kidney of plumbism is the “genu- ine contracted kidney,” an extremely slow and chronic but con- stantly progressive atrophy of renal tissue and its substitution by cicatricial tissue. Kobert says there is no metallic poison which has so characteristic an effect on the kidney as lead. The excretion of even small quantities exerts an injurious effect on the cells of the parenchyma, destroys them, and eventually sets up a true cirrhosis, which, according to v. Leyden (53), is identical with Virchow’s atrophic granular kidney. The first stage is one of typical glomeru- lar ischemia, with very marked secondary degenerative changes in
* Hyslop and Kraus (Arch. Neurol. and Psychiat., 1923, 10, 444) review the literature on the pathology of lead paralysis and point out that lesions have been found in every part of the neurone, from the cord to the muscles. The term, peripheral neuritis, is therefore inaccurate and they suggest instead, “toxic neuronitis.”
t The typical kidney of chronic lead poisoning has never been reproduced in animals, doubtless because the exposure to lead can never be prolonged for years as it is in human beings. (Jores (7), von Jaksch (51), Kobert ( 42).)
INDUSTRIAL POISONS IN THE UNITED STATES 29
the parenchyma, and, as it goes on, there is an endarteritis obliterans, involving especially the smaller vessels (Volland (54), Mohr (55), and Staehelin (56)). There is also sometimes a subacute form of renal plumbism, with marked edema, and here the pathological changes are mixed; for there is not only thickening of the vessel walls with occlusion of the lumen, but a marked degeneration of the convoluted tubules. The endothelium of the glomerular loops thickens, and hard shining hyaline masses result. It is especially in the very finest vessels that these changes come out most clearly. The later stages of the lead kidney conform absolutely to the type of secondary contracted kidney. The process is one of repeated vaso-constrictor spasm of the renal vessels, then endarteritis, then ischemia, dropsy, degeneration of the epithelium of the convoluted tubules, and then, as the narrowing and occlusion of the vessels pro- ceeds, proliferation and contraction of connective tissue (Volland). It is characteristic of the contracted kidney of chronic plumbism that it may exist for years without giving any sign and may betray _ itself first by an uremic encephalopathy. The urinary findings are what one expects from such a pathology,—abundant urine low in solids, absolute diminution of urea, as well as of uric acid and of phosphoric acid, but symptoms of urea retention may not appear for a long time. Albumin may be absent and the microscope may show only hyalin castes, few leucocytes, rarely red blood cells. There is hypertrophy of the left ventricle of the heart in such cases, but usually this is not discovered till the heart begins to wear out. Later, the right heart enlarges. Uremia supervenes when the heart can no longer overcome the obstacles to circulation in the kidney, either because of cardiac overstrain or of extension of the process in the kidney. Dropsy may be entirely absent, and indeed it is commonly _ said to be, but in the later stages it appears in the ankles and below _ the eyes. Headache, before the onset of uremia, may come from _ the high blood pressure, causing active, cerebral hyperemia. Albumin- uric retinitis, with hemorrhages and white spots in the retina, has been repeatedly described in chronic plumbism. Von Jaksch finds always in chronic lead poisoning an increase in formation and excre- _ tion of urie acid which is an evidence of increased breakdown of _ nuclein bodies, caused, he believes, by lessened oxidation. Arthral- _ gias and gout are explicable on the ground of retention of uric acid and its salts. Liithje (57) rejects this explanation of saturnine gout, _ and holds that lead has no influence on the excretion of uric acid, and _ does not cause urie acid retention, but increases uric acid produc- _ tion, as shown by the abnormal quantity of the latter in the blood. _Preti (58) found, in three chronic cases, that the total elimination _of purin bases was over the normal, and, even on a purin-free diet _ there was an excess of uric acid in the blood (Gétze (59)). Ram- _ bousek (60) fed rabbits with white lead by stomach tube and found
30 INDUSTRIAL POISONS IN THE UNITED STATES
in all an increase in total purin excretion, rising strikingly as the symptoms of poisoning increased. The increase in uric acid was not constant, appearing in the early stages, but not in the later, and apparently ceasing when real injury to the kidney had occurred, as shown by albuminuria. These disturbances of elimination he be- lieved to be the direct effect of the lead, and not an indirect action induced by the production of structural changes in the kidneys.
Gastro-intestinal Tract.—FThe gastro-intestinal symptoms are the most striking of all in ordinary acute lead poisoning, and yet the pathology of lead colic has not been the subject of nearly so much study as have other features of plumbism. Animal experiments are of limited value; for typical lead poisoning in animals is charac- terized by diarrhea, not by constipation (Harnack (61), Meillére (62)). That lead colic is preceded by constipation and accompanied by extreme contraction of the intestine is notorious, and the clinical treatment is based on this fact. As to the exact mechanism of these contractions, however, and their relation to the colic, opinions differ. The action of the lead may be a local irritation exerted directly on the smooth muscle fibers (Eulenberg (63), Guthmann (64), Hitzig (65) ), or a stimulus to the nervous apparatus which governs the intes- tinal movements, causing in animals diarrhea, in man, obstinate con- stipation (Harnack). The pain is usually accounted for by the violent spasm of the smooth muscle of the gastro-intestinal wall, but by some it is believed to be a neuralgia of the sympathetic system.
The fact that the blood pressure is heightened during colic and that both pain and hypertension are relieved by amyl nitrite, led Pal (66) to assume a specific irritation of the vasomotor nerves of the abdominal sympathetic, with constriction of the intestinal blood vessels as the cause of colic. Albertoni (67) and Annino (68) and Ruffino (69) find the origin of such vaso-constriction in the action of lead on the vasomoter center. Kobert made experiments on ani- mals in the warm chamber with the abdomen open and came to the same conclusion as Pal, namely, that lead causes an intermittent irritation of the nerves of the intestinal blood vessels and of the muscular walls. Atropin and scopolamin, which have a paralyzing action on the peripheral ends of these nerves, act like a charm on lead colic.
Siceardi (13) criticizes most of these investigators on the ground that they have studied the indirect effect of lead in the circulating blood instead of its direct local action in the intestinal tract. In order to correct this error he observed the action of the neutral acetate of lead on the isolated intestine, choosing this compound because like all organic salts it is poorly ionizable and therefore has little action on albumin. He employed Magnus’ method of regis- tering the movements of the intestines of a guinea pig immersed in Ringer-Locke solution at 88° C. The rhythmic contractions being
INDUSTRIAL POISONS IN THE UNITED STATES 31.
well maintained, he could detect the slightest variations when intro- ducing an isotonic solution of the lead salt in varying quantities. Fifty such observations were made on the small intestine, colon, and rectum, as a result of which Siccardi declares that lead in the intes- tinal tract exerts two effects: one on the movements of the intestine, and one on.the tone, these actions varying according to the dose and the part of the intestine involved. The changes in intestinal motility consist first in a lowering of tone with diminution of rhythmic movement, but this hypotonicity, under the influence of an accumu- lation of lead, yields suddenly to a state of hypertonicity with arrest of rhythmic movements which persists till the lead is eliminated. In this way constipation passing into colic is produced. Siccardi was, however, unable to say whether the mechanism which produces lead colic is a direct action on the smooth muscle fibers, or on ganglia or nerve ends, or on all simultaneously.
Rigel (70) studied 200 cases of lead colic and decided that there was a toxic vaso-spasm of the abdominal vessels, due to an irritation of the vaso-constrictor nerves, the pain and the contraction of the intestinal wall being secondary. Walko (71) refuses to accept this explanation; for he has seen a normal or even a low blood pressure during colic, so that vascular spasm cannot be responsible, nor can spasm of the intestinal musculature be responsible; for the muscles may be actually atonic. He believes that it is a neuralgia of the mesenteric plexus, as was suggested by Romberg (72), similar to the lead neuralgias in the limbs. Debove (73) explains lead colic as a neuralgia of the celiac plexus and quotes a thesis of Levatier, who succeeded in producing sclerotic changes in the solar ganglia in animals by the administration of lead, and who also saw similar changes in man. Excitation of the fibers of the celiac plexus affects the smooth muscles of intestine, vessels, uterus, ete.
Years ago Tanquerel found in one of his autopsies a striking en- largement of the abdominal ganglia of the sympathetic, which were two or three times their normal size. Then Kiissmaul and Maier found proliferation and contraction of the connective tissue of the septa of several ganglia of the sympathetic, especially the celiac, in a man who died during an attack of lead colic. Mosse (74), work- ing on the ganglia of lead poisoned rabbits, found distinct degen- erative changes in the cells, but since similar changes could be pro- duced by other drugs which have the property of setting up intes- tinal contractions, such as berberin, he concluded that these changes were the result, not the cause, of the colic. He subjected the ganglia to analysis in Salkowski’s laboratory and was able to show tlie pres- ence of lead. The actual pathogenesis of lead colic remains, there- fore, still an unsolved problem.
In chronic lead poisoning Kiissmaul and Maier (6) found a thickening of the submucous coat of the stomach and intestines (due
32 INDUSTRIAL POISONS IN THE UNITED STATES
to connective tissue proliferation and to thickened vessel walls), endarteritis, and atrophy of the glands, plaques, and follicles of the jejunum, ileum and the upper part of the colon. Maier (2) also succeeded in producing experimentally a cloudy swelling of the glandular cells in the stomach; later granular and fatty degenera- tion; numerous ecchymoses; thrombosis of arteries, veins, and capil- laries; thickening of the submucous coat. Similar but less striking changes appeared in the intestine. Kobert speaks of a gastritis glandularis with disappearance of glands, and thickening of the walls of the stomach. McJunkin (75) found in animals a necrosis of the gastric epithelium and of the cells of upper parts of the glands, which reached its height at the end of twenty-four hours, and then gave way to a regenerative process with proliferation of epithelium and phagocytosis of the necrotic cells. This process, well established at the end of 48 hours, was complete in 72 hours.
Walko, whose work on the gastric pathology of lead poisoning has already been quoted (71), concluded that at the beginning of the disease there is a functional disturbance which shows itself in a lessening or complete disappearance of acid and ferment formation, and further in a heightening of the activity of the stomach, which is succeeded by a diminution of motility. These disturbances are very obstinate and protracted, but are usually purely functional, rarely accompanied by parenchymatous changes in the mucosa, and partly affected by constipation and by disease of the gastro-intestinal nerve plexus. Preti (58), examining the gastric juice during colic found anacidity or hypoacidity, and Allevi found the same condi- tion. . Blood.—Lead causes a secondary anemia, which is seldom of a pronounced type, the blood count usually running between four and five million and the hemoglobin 80 per cent or over. (See chapter on lead diagnosis.) The changes in the white cells are not charac- teristic and most students of the blood picture in lead poisoning do not find striking changes in the red cells.
In Cadwallader’s (76) blood examinations both micro- and macro- cytes were commonly seen, and in 33 of his 37 cases there was always at least one normoblast. Myeloblasts were seen in only two, one of which presented an unusual picture,—no less than 130 normo- blasts and 13 megaloblasts (to 500 whites) and yet the red cell count was reduced only one-fourth.
Cabot (77) says that in lead poisoning there may be an extraor- dinary number of nucleated reds, and this, in the absence of any other evidence of severe anemia, such as‘achromia or poikilocytosis. Among these nucleated red cells a very considerable proportion, occasionally a majority, may be megaloblasts. Simon and Spillman (78) also find megaloblasts in experimental poisoning, yet there are cases of extreme anemia in which these youthful forms are lacking,
SCS
INDUSTRIAL POISONS IN THE UNITED STATES 33
showing that the hemopoietic tissues no longer respond to the call for fresh corpuscles. ‘Thus in the very interesting case described by Wolff (79) of a man dying after more than ten separate attacks of lead poisoning, the hemoglobin had fallen to 40 per cent, the red cell count to 1,250,000, and there were no immature forms to be found.
It is the presence in the blood of more or less abnormally staining red cells which has attracted great attention and has been the subject of lively controversy. These cells are polychromatophilic or reticu- lated or “stippled,” 7.e., filled with granules which take up basic stains. The granules appear when the blood is stained by Wright’s method, or by any other basic stain, as fine or coarse granules, some- times so fine and so closely packed together as to give the appearance of a purplish discoloration of the protoplasm; sometimes as dots of coarse granules, few in number; sometimes as both powdery and coarse grains. These stippled cells have been interpreted in many ways, but the clearest description of their origin was first given by Craik (80) and his findings have recently been confirmed and elabo- rated by Key and by Aub and Reznikoff.*
Craik, who was studying malaria, noticed incidentally the appear- ance of polychromatophilic cells in men under the influence of lead. He administered lead acetate to patients who were suffering from mild infection. Four days after the dose was given he could find young forms of the parasite, rings, in normal red cells and in poly- chromatophilic cells, but only young forms were ever found in the latter. The later stages of the parasite, amebic forms, and large pigmented forms, were found only in normally staining cells with or without stippling. Craik thinks that this shows that within 24 hours the polychrome cell has grown to a normal cell and the poly- chrome stippled cell to a normally staining stippled cell. Poly- chromasia means premature birth of erythrocytes; punctate baso- philia means something more pathologic. Even in mild anemia, the former is rarely absent, but the latter is rarely present in any- thing but profound anemia, with the exception of lead poisoning.
_ Only when punctate basophilia is seen in otherwise normal blood, - associated with but little polychromasia, is it pathognomonic of
plumbism. A loss of elasticity and a heightened resistance to hemolysis has
_ been noted as an effect of lead. At the First International Congress
of Industrial Hygiene, held in Milan in 1906, Glibert (81) of Brussels spoke of a marked loss of elasticity of the red corpuscles as
a result of lead poisoning, claiming that this was a good diagnostic
sign. His statement led Rambousek to look for a heightened resist-
ance to hypotonic and to hemolytic substances on the part of such red cells, but in experimental plumbism he was unable to find any
* Harvard Lead Studies, not yet published when this goes to press.
34 INDUSTRIAL POISONS IN THE UNITED STATES
change toward hypotonic salt solution and the resistance to hemolytic substances, saponin and potassium hydrate, was actually lowered. According to Rambousek, Roulens reported analogous findings at the Congress of Hygiene in Berlin in 1904. Four years later, at the Second Congress of Industrial Hygiene in Brussels, Meillére stated that he had found in lead poisoning an increased resistance to hemolysis and he placed this phenomenon among the diag- nostic signs of plumbism. Hayem (82) finds increased viscos- ity of the blood and loss of elasticity on the part of the red cells. Orban (83) and Malassez (84) find increased resistance to hemol- ysis.
The recent work of Aub and his colleagues, Anne S. Minot, J. A. Key, Paul Reznikoff and D. E. Smith, has thrown much light on the action of lead in the body, on its absorption, storing and excre- tion and on the effect of lead on the red blood corpuscles. They have found that lead is carried largely in the plasma of the blood as an insoluble triple phosphate but it is also partly picked up by the red blood cells, uniting with the phosphates of the cell membrane to form insoluble lead phosphate on the surface of the red cells. The effect of this is to make these cells hard, brittle and inelastic, an effect noted, although not explained, by other observers. These red cells break up more easily than-do normal cells, which fact explains the high peripheral blood destruction in lead poisoning with the resulting anemia. There is a loss of the normal stickiness of the red cells, a shrinking, even in isotonic solution, a loss of normal elasticity and an increased resistance to changes in external osmotic pressure, but at the same time an increase in the speed of disintegra- tion, “leaded cells break up more readily on standing than do normal cells and are easily fractured by rotation or shaking.”
The anemia calls forth the production of young blood cells, reticu- lated corpuscles, but these under the attack of the lead in the plasma undergo degeneration and this degeneration is shown by basophilic clumping of the reticulum. The so-called stippled red cells are therefore degenerating reticulated corpuscles and they are the result of the response of the blood building tissues to the anemia caused by lead and the destructive action of lead upon the newly formed red cells.
The effect of lead poisoning on the white cells of the blood is less striking and, according to the majority, less constant. Grawitz (85) says that a marked leucocytosis is a frequent occurrence, and there are likely to be numerous atypical forms, giving the blood a “leuk- emoid” appearance. Key found a leucocytosis in experimental plum- bism in rabbits, the increase being chiefly mononuclear, large lympho- © cytes and large mononuclears. (See chapter on diagnosis. )
Bone Marrow.—Changes in the marrow of the large bones have been described by Jores (7) as consisting in a loss of fat, slight pig-
——-— =
INDUSTRIAL POISONS IN THE UNITED STATES 35
mentation and increase of cellular elements. In experimental poison- ing carried to the point of marked anemia, the disappearance of fat from the marrow and the increase of cellular elements, especially of the hemoblasts, is followed by disappearance of the latter and by a gelatinous degeneration (Raimondi (86), Stockman (87) and Char- teris). In Wolfi’s (79) case there was extreme anemia and no evidence in the blood of any regeneration of cells. The marrow showed abundance of cellular elements, but they were non-granular, and nucleated’ reds were absent.
The study made by Cadwallader (88) on human bone marrow in severe plumbism yielded interesting results. His case was one of fatal encephalopathy, but unfortunately no blood examination was made before death. ‘The marrow in the ribs and at the ends of the femur was a deep purple, but in the shaft of the femur it was yellow and fatty. Microscopic examination of the head of the femur re- . vealed marked hyperplasia of marrow cells, producing in some places almost solid marrow. The most striking feature was the great num- ber of nucleated red cells which formed large, compact masses. In the center of such a mass the cells were very large, closely packed, and the nuclei showed irregular figures; but at the edges they were looser and smaller, and looked like normoblasts. Between these areas were spaces filled with white cells,—chiefly granular myelo- eytes, transitionals, few eosinophils and polymorphonuclears, and a moderate number of large and small lymphocytes. The hyperplasia of the leucoblastic tissue produced chiefly granular myelocytes, some of which had karyokinetic figures.
The discovery by Anne Minot * that the greater part of the lead in chronic plumbism is deposited and stored in the skeleton suggested to her the possibility that the anemia of plumbism might be due to the localization of the lead in the marrow of the bones and a conse- quent injury to the growing red cells. She found, however, that this theory was not borne out by further experimental study. Analyses made of solid bone deprived of marrow, of leaded animals, and of marrow separated from bone, showed that the lead was deposited in the solid shaft, not in the marrow. Moreover, she found that when hens were poisoned with lead the marrowless pneumatic bones of the wings contained a considerable amount of lead. Another con- firmation of these findings is the fact that relatively large amounts of lead may be held temporarily in the skeleton without the appear- ance of anemia.
Spleen.—In the spleen, Jores (7) found the most marked change to be (in experimental poisoning) a massing of blood pigment in
the cells of the pulp. Yet, in spite of the great quantity of this _ pigment, there is no enlargement of the spleen. Wolff (79) found
* Harvard Lead Studies, unpublished.
86 INDUSTRIAL POISONS IN THE UNITED STATES
in the human spleen a myeloid change—the presence of numerous nucleated red cells, which were lacking in the bone marrow.
“Kndlessly varied and complicated is the picture of chronic lead poisoning,” von Jaksch has said. ‘Always that part of the budy suffers most which has been the seat of some previous disease, whether it be kidneys, central nervous system or vascular system. It is impossible to explain all the manifestations on the ground of the action of lead on one tissue only, such as on the smooth muscles, the vessel walls, the nerves of the sympathetic system; but there are certain tissues which seem to be especially susceptible to its effects, —namely the vascular walls, the bone marrow, the motor neurones, and parts of the sex organs.” (89)
BIBLIOGRAPHY
(1) TanquerEL pes Piancues, L. Lead Diseases, a Treatise from the French of L. Tanquerel des Planches, translated by Samuel L. Dana, Lowell, 1850.
(2) Mater, R. “Experimentelle Studien iiber Bleivergiftung.” Virchow’s Arch., 1882, 90, 455-481.
(3) Exscunie, A. “Sehstérungen durch Bleivergiftung,” Wien. med. Wcehnschr., 1898, 48, 1805-1411.
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(5) WesreHaL, A. “Ueber Encephalopathia Saturnina,” Arch. f. Psy- chiat., 1887-88, 19, 620-664.
(6) KussmauL, A., and Mamr, R. Deutsch. Arch. f. klin. Med., 1872, 9,
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(8) Rosenstein. Virchow’s Arch. f. path. Anat., 1867, 39, 1.
(9) Hirzic. Studien tiber Bleivergiftung, Berlin, 1868.
(10) Hentz. Ztschr. f. rat. med., 1846, 4, 454.
(11) Goucer. “Saturnisme expérimentale: Hypertrophie considérable des capsules surrénales. Sclerose aortique.” Compt. rend. Soc. de Biol., 1903, 55, 1659.
(12) Brrnarp, G., and Bicart. “Etude anatomo-pathologique des capsules surrénales dans quelques intoxications expérimentales,” J. de phys- iol. expér., 1902, 4, 1014.
(18) Siccarpr, P. D. “Sur Vaction du plomb,” Arch. Ital. de Biol. (French), 1914, 62, 1-30; also “Azione locale del piombo sui movi- rat ritmici e sul tono dell’intestino,” Arch. per le sc. med., 1913, 37, 58.
(14) THoma. Quoted by Elschnig (3).
(15) Time, W. “Obliterative Arteritis and Lead Poisoning,” Lancet, 1916, 2, 162; also “A Case of Endarteritis Obliterans.” Bost. M. and S. J., 1916, 74, 539.
(16) Von Monakow, O. “Zur pathologischen Anatomie der Bleiliihmung und der saturninen Encephalopathie,” Arch. f. Psychiat., 1880, 10, 495, 526.
(17) Serrrert. Quoted by Westphal (5).
(18) OxELLER. Quoted by Westphal (5).
INDUSTRIAL POISONS IN THE UNITED STATES 37
(19) Oppennem, H. “Allg. u. Spez. iiber die toxischen Erkrankungen des Nervensystems,” Berl. klin. Wchnschr., 1891, 28, 1157.
(20) QurenseL. “Zur Kentniss der psychischen Erkrankungen durch Bleivergiftung,” Arch. f. Psychiat., 1902, 35, 612.
(21) Mosny, E., and Hervirr, P. “La méningite saturnine aigué,” Bull. et mém. Soc. méd. d. hép. de Paris, 1907, 24, 1344.
Mosny, E., and Matuomwet. “La méningite saturnine,” Rev. de méd.,
1907, 27, 505-659.
(22) Miurr. - Am. J. M. Se., 1892. yn. s. 111, 198.
(23) Ménirrrer, P. “Encephalopathie saturnine et hypertension arteri- elle?’ Bull. et mém. Soc. méd. d. hép. de Paris, 1904, Series 3,
21, 141. (24) Trause. Ann. Rept. Chief Inspector Factories and Workshops, 1912, 203
(25) WYnTerR Buiytrn, A. “Distribution of Lead in Brains of Two Lead Factory Operators,” J. Mental Sc., 1887-8, 33, 483.
(26) Goapspy. Ann. Rept. Chief Inspector Factories and Workshops, 1912, 203
(27) Cent. Arch. f. Psychiat., 1897, 29, 566. ;
(28) Jotny. “Ueber Blei- und Arseniklihmung,’ Deutsch. med. Wehnschr., 1893, 97-99.
(29) Hermann. ‘Teber die Bedingung des Zustandekommens von Ver- iced Arch. f. Anat., Phys., u. wissensch. Med., 1867, Series
(30) Sy Inn. Zentralbl., 1891, Series 44.
(31) Nisst. “Ueber experimentell erzeugte Veriinderungen der Vorder- hornzellen,” Allg. Ztg. f. Psychiat., 1892, 48, 675; «bid., 1897, 54, 1.
(32) Hassin, G. B. “The Contrast between the Brain "Lesions Produced by Lead and other Inorganic Poisons and those caused by Epidemic Encephalitis,” Neurol. and Psychiat., Sept., 1916, 6, 268-285.
(83) Camus, J. “Méningite et see saturnine,”’ Compt. rend. Soc. de biol., 1912, 72, 861.
(34) VuLPIAN. Quoted by Kobert (42).
(35) Repuicu, E. “Tabes dorsalis und chronische Bleivergiftung,” Wien. med. Wcehnschr., 1897, 47, 801 and 861.
(36) Ercunorst, H. “Ueber Bleilahmung,’ Virchow’s Arch., 1890, 120, 2
a7.
(87) Remax. “Neuritis and Polyneuritis,’ Nothnagel’s Spez. Therap., Vienna, 1899, part 3, 11, 279.
(88) Gorvon, A. “Atrophy of the Intrinsic Muscles of the Hands due to Lead Poisoning,” New York M. J., 1906, 88, 1125; also J. Nerv. and Ment. Dis., 1906, 33, '730.
(39) CuHarcor and Gompautt. Arch. de Phys. norm. et path., 1881, Series 2, 8, pp. 126-159.
(40) Desertne-KitumpeKer. Des polynévrites en général et des paralysies et atrophies saturnines en particulier, Paris, 1889, 295.
(41) Srieerirz, L. “Eine experimentelle Untersuchung iiber Bleivergif- tung mit besondere Beriicksichtigung des Nervensystems,” Arch. f. Psychiat., 1892, 24, 1.
(42) Kopert, R. Lehrbuch der Intoxikationen, Stuttgart, 1906, 2, 375.
(43) Spmier, W. G. “The Pathological Changes in the Nervous System in a Case of Lead Poisoning,” J. M. Res., 1903, 10, 142.
(44) Mircnent, J. K. “Amyotrophic Lateral Sclerosis of Lead Poison- ing,” J. A. M. A., 1910, 1, 313.
(45) Capwatiaper, W. B. “Amyotrophy of Lead with Increased Reflexes,” J. Nerv. and Ment. Dis., 1912, 39, 153.
388 INDUSTRIAL POISONS IN THE UNITED STATES
(46) Herter, C. A., and Van Gieson, Ira. N.Y. M. J., 1895, 61, 665.
(47) Lastert, FE. E., and Warrineton, W. B. Brain, 1898, 21, 294:
(48) Bricut. See v. Leyden (58).
(49) Outivier. “De l’albuminurie saturnine,”’ Arch. gén. de Méd., 1863, 2, Series 6, 530.
(50) Wacner, E. Handbuch der Speziellen Pathologie und Therapie.
(51) Von Jaxscu. Die Vergiftungen. Vienna, 1910, 193.
(52) Srrimpe tt, A. Textbook of Medicine, 2nd American ed. New York, 1896, p. 856. :
(58) V. Leypen, E. Ztzchr. f. klin. Med., 1884, 74, 88.
(54) Votuanp. “Histologische Untersuchung bei epileptischen Krank- heitsbildern,” Ztschr. f. d. ges. Neurol. u. Psychiat., 1914, 21, 195- 241,
(55) Mour. Quoted by Volland (54).
(56) SragneLIn, R. “Epidemic Encephalomyelitis,’ Schweiz. med. Wcehnschr., Mar. 11, 1920, 50, 201.
(57) Linge. “Bleigicht und Harnséiure Ausscheidung,” Ztschr. f. klin. Med., 29, 1896.
(58) Pret, L. Jl Lavoro, 1913, 6, 217.
(59) GoérzE. Quoted by Rambousek (60).
(60) Rampousex. “Beitrige zur Pathologie des Stoffwechsels und des Blutes bei chronischer Bleivergiftung,” Ztschr. f. exper. Path. u. Therap., 1909-1910, 7, 686.
(61) Harnack. “Ueber die Wirkungen des Bleis auf den tierischen Organ- ismus,” Arch. f. exp. Path. u. Pharm., 1878, 9, 152.
(62) Memuire. Le Saturnisme, Paris, 1903.
(63) EuLENBERG. Quoted by Mosse (74).
(64) GuTHMANN. Quoted by Mosse (74).
(65) Hirzic. Studien iiber Bleivergiftung, Berlin, 1868.
(66) Pat, J. “Ueber d. Darmschmerz,” Wien. med. Presse, 1903, 46, 57.
(67) ALBERTONI. Quoted by Siceardi (13).
(68) Annino. Quoted by Siceardi (13).
(69) Rurrino. Quoted by Siceardi (13).
(70) Ricet, F. “Beitrige zur Lehre von den Stérungen der Saftsecretion des Magens,” Ztschr. f. klin. Med., 1886, 11, 1.
(71) Watko, K. “Die Erkrankungen des Magens bei der chronischen Bleivergiftung,” Miinchen. med. Wehnschr., 1907, 54, 1728.
(72) Romperc. Quoted by Walko (71).
(73) Drsove. “Colique saturnine, sa pathologie,” Rev. gén. de clin. et de thérap., 1909, 23, 33.
(74) Mossz, M. “Zur Kentniss d. exper. Bleikolik.,” Ztschr. f. klin. Med., 1908, 50, 62.
(75) McJunxin, F. C. “The Local Action of Lead,” J. Med. Research, 1915, 37, 1469.
(76) CapwaLLapEerR, W. B. “A Study of the Blood in Lead Poisoning,” Univ. Penn. Med. Bull., 1906-7, 19, 68; also Bull. Ayer Clin. Lab., 1906, No. 3, 44.
(77) Casot, R. C. Clinical Examination of the Blood, N. Y., Ed. 5, 1904,
419
(78) Stmon and Spmumann, L. “Altérations du sang dans l’intoxication saturnine expérimentale,” Compt. rend. Soc. de Biol., 1906, 60, 765.
(79) Wotrr, A. “Haematologischer Befund bei einem Fall von schwerer Bleianaemie, zugleich ein Beitrag zur Haematopoiese,” Berl. klin. Wehnschr., 1902, 39, 840.
(80) Crark, R. “Effect of Lead on Erythrocytes,” Abstr. J. A. M. A,, July 8, 1920, 64.
INDUSTRIAL POISONS IN THE UNITED STATES 39
(81) Gripert. International Congress of Industrial Hygiene, Milan, 1906.
(82) Hayem. “Névropathie et Saturnisme,” J. de méd. int. de Paris, 1905.
(83) Orspan, R. “Ueber gewerbliche Vergiftungen mit Bezug auf die Lh Seu Blutprobe,” Deutsch. med. Wchnschr., 1912, 44, 2079-81.
(84) Manassez, L. “Recherches sur lanémie saturnine,’ Mém. de la soe. biologie, 1873, pp. 125-136.
(85) Grawirz, E. Klinische Pathologie des Blutes, Leipzig, 1911, 753.
(86) Rarmonpr, C. Ann. univ. de Med. e Chir., 1880, 149, 52.
(87) Srockman, R., and Cuarteris, F. J. “The Action of Lead, Mercury, Phosphorus, Iron, and Quinine on Bone Marrow in Rabbits,” J. Path. and Bacteriol., 1903, 9, 202.
(88) CapwaLLaper, W. B. “A Study of the Blood in Lead Poisoning with a Description of the Bone Marrow of One Fatal Case,” Bull. Ayer Clin. Lab. Penn. Hosp., Phila., 1906, 3, 44.
(89) Von Jaxsou, R. Die Vergiftungen, 2nd ed., Vienna, 1910, 186 and 193
(89) To be published.
CHAPTER 3 ABSORPTION AND EXCRETION. QUANTITY: ABSORPTION AND ExorErIon
Tuer mode of entrance of lead into the body is of the greatest practical importance; for it is obviously impossible to have an intelli- gent system of protection against lead poisoning unless there is a clear understanding of the relative danger of absorption through the skin, absorption through breathing lead dust, and absorption through stomach and intestines of lead which is carried into the mouth with food or tobacco. We must be able to say whether the prevention of dust and fumes is more important than the prevention of actual contact with lead and its compounds, and whether lead poisoning is best combated by provisions for bodily cleanliness or by provisions for keeping the air of working places free from lead.
Absorption through the skin is apparently possible, especially when lead is mixed with oil as it is in paint. The question has been a difficult one and observations in industry have helped little in set- tling it, because it is impossible to rule out other channels of absorp- tion in industrial cases, nor are the results obtained by animal experiments entirely conclusive; for they cannot be made to apply to men without reservations. Such experiments have been carried on ever since Tanquerel’s day, the latest work being that of Siiss- mann (1) one of Lehmann’s assistants, who published his experi- ments in 1922. He estimated the lead in the discharges of cats and guinea-pigs after anointing them with lead oxide mixed with ani- mal fats, all possible precautions having been taken against the entrance of lead through the mouth. Siissmann decided that lead was absorbed, because he found it in the feces and urine, but the amount was not large enough to cause poisoning except of a very slow and chronic type. Brezina and Eugling (2) in 1912 believed that they had succeeded in making lead pass through the skin of guinea-pigs anointed with lead in lanolin. They took the appearance of stippled cells in the blood as proof of the absorption of lead.
A. §. Minot (3) injected subcutaneously doses of 220 mg. of a sterile suspension of lead carbonate into six cats. These animals were kept in metabolism cages and though no attempt was made to
obtain total recoveries, the lead excretion in urine and feces was studied from time to time. Small amounts of lead (2 to 3 mg. per
40
INDUSTRIAL POISONS IN THE UNITED STATES 41
week) were constantly excreted in the feces and occasional traces appeared in the urine. After four months, during which the only indications of lead intoxication were definite lead lines in certain of the animals, two of them were killed and their tissues analyzed. The total amounts of lead found in the body, aside from the still - unabsorbed deposit at the site of injection, were 25.72 and 29.2 mg., respectively. Of this, about 90 per cent was in the skeleton, most of the remainder, in the liver and gastro-intestinal tract.
It appears from experiments such as these that it is possible to make lead pass through the skin of an animal into the subeutaneous tissue and that lead can be slowly absorbed from the subcutaneous tissue and distributed throughout the body, finding its final lodgment chiefly in the skeleton. If this can be shown in animals kept under observation for a few months only, the possibility of chronic lead poisoning in man through skin absorption cannot be denied. Painters who have their hands and forearms smeared with white lead in oil for eight hours a day and for many months out of the year may be assumed to absorb from the skin quantities of lead which are probably very small but which throughout the years slowly accumulate in the skeleton. As we shall see presently, a slow, continuous stream of lead, even in minute quantities, can set up the changes characteristic of chronic plumbism.
Whatever be true of the possibility of skin absorption of lead, its practical importance in industry is slight compared with the im- portance of absorption through the inspired air or even absorption of lead which is conveyed to the mouth on food or tobacco by hand- ling it with lead-smeared fingers. This latter mode of poisoning has always been emphasized by employers and foremen, and the respon- sibility for an attack of lead colic placed upon the individual work- man who supposedly should protect himself by careful washing of his hands and face. There is no practical evidence that this mode of poisoning is of much importance. It is true that a small amount of lead may reach the mouth from the fingers, but except in the ease of painters, the men who get lead on their hands are almost always exposed also to lead dust and fumes in the air, and the inci- - dence of poisoning can be traced with much more positiveness to the latter source. Even with painters the dust caused by dry rub- bing is a factor far from negligible.
I know of but one occupation in which lead poisoning by direct ingestion is of common occurrence. This is the work of the com-. mercial artist, or “retoucher,’’ whe touches up the shadows and the high lights of photographs for catalogues, advertisements, ete., in order to make them reproduce better. These men and women use a fine camel’s hair brush and white lead paint, and many of them have the habit of putting the brush in the mouth to bring it to a point. They sometimes suffer from very severe forms of lead poison-
42. INDUSTRIAL POISONS IN THE UNITED STATES
ing, especially as many of them do not know that the paint they use contains lead.
Among European authorities there has been practical agreement for many years that the great danger for the lead worker comes from contamination of the air by lead dust and lead fumes, which are essentially the same, lead fumes being merely a suspension of very finely divided lead compounds. Almost a century ago Tan- querel emphasized this, saying: “All the characteristic traits of the primary effects of lead may be quickly observed in workmen who are habitually in an atmosphere of lead dust and vapors. None of the primary effects are found among the workmen who handle lead in a fixed state and who consequently are never in contact with an atmosphere where particles are disseminated. . . . All those indi- viduals who are habitually in the midst of an atmosphere filled with lead particles or emanations are liable to lead encephalopathy.” . Tanquerel even went so far as to say that lead palsy is found only in those whose work exposes them to ‘‘emanations of lead dissemi- nated through the atmosphere.”
A French authority of later years, Breton (4), also lays the greatest stress on the danger of dust and quotes Gauthier’s report on lead poisoning in the Department of the Seine from 1900 to 1911, which showed that out of 1,000 white lead workers who had their hands in wet white lead, only 50 became poisoned; but out of 1,000 who handled dry white lead, 105 were poisoned. Out of 1,000 solderers working in an atmosphere full of fine dust and fumes, 280 showed evidences of plumbism.
In England the danger of lead dust is recognized and the pre- ventive measures enforced by the Department of Factory Inspection of the Home Office are directed especially against dust and fume contamination of the air, with brilliant results, as will be evident to any visitor of the potteries of North Staffordshire and of the white lead works in Newcastle-on-Tyne. In the latter city I saw men with their arms smeared up to the shoulders with white lead, but this was not looked upon as a risk because ample facilities were provided for the men to get rid of the lead at noon and at quitting time. Sir Thomas Oliver (5), to whom the reforms in this indus- try are due, had laid stress especially on dust prevention, and in that year, 1910, only five cases of lead poisoning had developed among 1,320 employed. Some years later when I visited the potteries I saw the same principle applied, of meticulous dust prevention, and here, too, there have been remarkable results. There were in 1913 in British potteries only 62 cases of plumbism among 7,085 em- ployees, a rate of less than one per cent.
Legge and Goadby (6) say that the poisonous nature of any lead compound from an industrial point of view is proportional, (1) to _the size of the ultimate particles of the substance manufactured and,
_ Le
INDUSTRIAL POISONS IN THE UNITED STATES 48
therefore, to the ease with which such particles are capable of dis- semination in the air, and (2) to the solubility of the particles in the normal fluids of the body. In short, the toxicity of a lead com- pound depends first on a physical property—its dustiness, and sec- ond, on a chemical property—its solubility.
Teleky says that in a large factory in Austria in which 80 tons of white lead were used in indoor work in a year’s time, 163 cases of lead poisoning developed among the indoor workmen, while among the outdoor men who handled almost three times as much, 237 tons, there were only 50 cases. General recognition of the special danger to painters, of the dust produced by dry rubbing of white lead paint, has led to the prohibition of such work in many European countries. I have a list of 100 Chicago painters who were treated for plumbism and who averaged twenty years in the trade, but among them were 11 who sickened in less than one year and these 11 had all been doing interior decoration with dry rubbing. Another comparison can be made between the bag house and flue cleaners in a Utah smelter and the men in the refining department. The former were shoveling and transporting flue dust which contains about 45 per cent * of lead, and 62.5 per cent of these men had plumbism. . The refiners were handling pure lead, but there was very little dust, and only 14.3 per cent had plumbism.
The cumulative evidence of the over-weening importance of lead- laden air has had its effect on governmental regulations, and British authorities at present hold that the question of personal cleanliness on the part of the worker is of minor importance, that ‘‘very little trouble is brought about by not washing hands” (Goady (7)) and that “unless you can go to the fountain-head of the mischief, the dust, and stop that, you are not going to secure much improvement by all the personal cleanliness in the world.” (Legge.) The Ger- man smelting expert, Richard Miiller (8), estimated that a blast- furnace tapper could breathe as much as 1.0625 gm. of lead in a ten-hour day, but that it was possible to wash off his hands only 0.0876 em., and of course it is absurd to think that all of that could be wiped off on his food and reach his mouth.
Practical evidence of the supreme importance of the respiratory tract as the channel of entry for lead seems, therefore, to be incon- trovertible, but there has been much difference of opinion as to the exact way in which poisoning takes place when dust and fumes are breathed in, whether the lead actually reaches the lungs or is simply caught in the mucus and saliva and swallowed. Meillére(9) holds that absorption through the lungs is of very slight importance, that the gastro-intestinal tract throughout its whole extent is the place where absorption occurs. Many efforts have been made to follow the ©
* Hofman, H. O., Metallurgy of Lead, New York, 5th ed., 1899, p. 379.
44 INDUSTRIAL POISONS IN THE UNITED STATES
lead introduced experimentally and determine the exact course it follows. Stieglitz (12) poisoned 13 guinea-pigs and 10 rabbits by a spray of lead acetate solution, wishing to reproduce the conditions under which industrial poisoning in man takes place, but it is im- possible to accept his experiments as a proof of respiratory absorp- tion because he made no attempt to protect the animals’ bodies and he admits that the fur was often soaked with the solution. Lepidi- Chioti is said by Roth (13) to have made successful experiments as early as 1880, introducing lead acetate into animals by blowing dry powder through a tracheal fistula and proving that lead had penetrated into the body.
The experiments carried out in K. B. Lehmann’s (10) laboratory to determine this point have been very widely quoted; these were both human and animal experiments. Two of Lehmann’s assistants, Saito and Gfrori, breathed in powdered white lead, inhaling through the nose and exhaling through the mouth. Saito found that he ex- haled 10 per cent of the quantity inhaled, that 51 per cent was caught in the nose, and 3 per cent in the mouth, and the remaining 36 per cent he assumed had passed to the lungs. Gfrori exhaled only 2.8 per cent, and the amount calculated to have reached his lungs was 43 per cent. When they breathed through the mouth they found 15 per cent was caught in the mouth and they believed that the lead in mouth and nose was eventually swallowed with the mucus and saliva.
When, however, they turned to animal experiments, using five dogs and one rabbit, to verify these findings, they obtained quite other results. There were, of course, great technical difficulties which they tried to overcome by placing the animal in a wooden box with his head thrust through a hole into the dust cylinder and fixed there with rubber bands. They introduced the dust through a nasal tube and fastened the lips together to prevent licking. Then the animals were killed and the lead estimated. They found much less in the respiratory tract than they had expected and much more in the intestinal tract. In five of the six animals the respiratory tract contained from four per cent to 24 per cent of the Jead, and the rest was in the stomach and intestines, showing that the greater part of the lead that had been blown into the nose and throat had been caught in saliva and mucus and reached the stomach, not the lungs. The sixth animal had 80 per cent of the lead in the respiratory tract, but this result was too exceptional for them to accept.
In this series Saito succeeded in recovering practically all the lead that had been introduced, but in experiments made on two dogs he could find only 14 per cent in one and 40 per cent in the other, because the dogs sneezed a great deal. However, in these animals, also, he found that 88 per cent and 60 per cent respectively of the
INDUSTRIAL POISONS IN THE UNITED STATES 45
lead that had gained entrance to the body had reached the digestive tract.
Goady also experimented in this field, but he came to a quite different conclusion. “That a certain amount finds its way into the stomach direct is not denied, but from experimental evidence we consider the lung, rather than the stomach, to be the chief channel through which absorption takes place.” Together with Goodbody (11) he made experiments on 35 cats, animals which are notori- ously susceptible to lead, and introduced finely divided lead dust into a closed chamber containing an electric fan to keep the air stirring. Samples of air were drawn off and the amount of lead estimated. Control experiments consisted in feeding cats 7 to 10 or even 20 times the amount. which calculation had shown that the dust-breathing animals could possibly take in. Yet these cats which were fed with lead showed little or no susceptibility to poisoning unless alcohol was added to the lead, while the animals breathing lead dust suffered from progressive emaciation and paralysis, and in many instances died with symptoms suggestive of involvement of the brain. Goadby succeeded in demonstrating lead as sulphid in the larynx, trachea, bronchi and bronchioles, by inflating with H.S and also “by micro-chemical tests with chromic acid and with iodin.”
As for the fate of lead in the body, the theory elaborated by Blum, and based not only on his own experiments but on those of many observers, has been generally accepted (14). After a compound of lead is absorbed by the body and reduced to an ionizable salt it is then transformed to an organic compound, to which is due the toxic action. This is probably an albuminate of lead from which the lead is slowly liberated and which is soluble in acids, in alkalies, and in an excess of albumin. The change from a non-absorbable form to an absorbable takes place in the stomach, but absorption oc- curs in the intestine. Blum was unable to trace its fate in blood and organs, but he succeeded in finding it in the blood of a rabbit three weeks after the administration of lead had stopped. It has, of course, been found in the organs by many investigators, but Blum does not feel sure that its presence there is directly harmful, though it may be that lead enters into combination with the tissue constituents, rendering them “lebensuntiichtig.” It can — combine with lecithin.
The fact that lead is found in altered tissue does not mean necessarily that it is responsible for this damage; it may have been deposited there subsequently to the damage. On the other hand,
1 quantities of lead have been found in a liver.showing no pathological
change. Blum believes that the action of lead is to be explained by its “special affinity for certain tissues, the smooth vessels in the
_ muscle walls, the motor nerves, the spinal cord, the blood-building
organs, the genital organs.” As for excretion, the kidneys play a
46 INDUSTRIAL POISONS IN THE UNITED STATES
minor role, the intestines the chief réle. Blum placed lead iodid and lead oxid in subcutaneous pockets and found that both com- pounds were changed to the carbonate and excreted in the feces, and that the same thing occurred, only far faster, if the salts were introduced into the peritoneum. He believes that the lead is trans- ported by the leucocytes. It is eliminated partly by the kidneys, but never in large quantities, and sometimes when the body is apparently flooded with lead it may be impossible to find any in the urine. Excretion takes place along the whole extent of the intes- tinal tract, no matter in what way the lead is administered, whether by the mouth, the respiratory tract, or by the subcutaneous tissues. An interesting confirmation of this was furnished by a non-indus- trial case of acute plumbism which was described by Kobert. A woman was given a vaginal douche of lead acetate which resulted in her death from acute lead poisoning, and the greater part of the lead absorbed from the vaginal mucosa was found in the intestines.
Many investigations have been made of the organs and tissues of animals experimentally poisoned and of human beings dying from various forms of lead poisoning. The literature on this subject up to 1906 has been collected by Kobert and the reader is referred for this earlier work to his book, “Lehrbuch der Intoxikationen,” Vol. 2, Stuttgart, 1906, page 375. Much of the data is conflicting and contradictory, partly because in many cases no analysis was made of the skeleton, partly because the methods of anaylsis used were not always such as to produce accurate results.
The whole field of controversy over the mode of entrance of lead into the body, the way it is transported, its absorption and storing and excretion, has been illuminated recently by the “Lead Studies” which were carried on at Harvard between 1922 and 1924, by Aub and his colleagues. airhall (15) has provided us with a new method of analysis, suitable for the determination of small amounts of lead in biological material,* and the work of Aub, Minot, Key, Reznikoff, Smith and Blumgart has cleared the obscurity from the subject of absorption and storing and elimination. Their investiga- tions furnish an explanation for the clinical observation of Tan- querel and others, that lead which enters the body by the respiratory tract produces its effect much more rapidly and severely than lead which enters by the gastro-intestinal tract. The curious instances of long periods of quiescence, of latency, in lead poisoning, with a
* Fairhall’s method of quantitative analysis consists briefly in (a) ashing the organic material at a low heat, (b) precipitating the lead as sulphid from a solution of the ash, (c) reprecipitation of the lead as chromate from a solution. of the sulphid, and (4) determination of the lead present by iodometric titra- tion. In this determination the chromic acid derived from the lead chromate precipitate reacts with an excess of potassium iodid, the liberated iodin is then titrated against a standard sodium thiosulphate solution, starch being used as the indicator. This method can be applied directly to the analysis of excreta or of small amounts of tissue.
INDUSTRIAL POISONS IN THE UNITED STATES 47
sudden recurrente of symptoms, is also explained by their experi- ments.
Anne Minot’s paper contains a critical review of the analyses made by Gusserow (1861), Heubel (1871), Ellenberger and Hof- meister (1887), Prévost and Binet (1889), Meillére (1903), and Kisskalt and Friedman (1914). The general conclusion drawn from these studies is that lead tends to become localized and stored in the bones. As for the actual way in which poisoning takes place, Miss Minot quotes as the most significant studies those of Straub and of Erlenmeyer. The “lead stream” theory to explain the funda- - mental mechanism of lead poisoning was developed by Straub (16) and by Erlenmeyer (17). Both investigators injected lead carbonate or sulphate subcutaneously in cats, the compounds were gradually absorbed and in the course of a few weeks the animals developed chronic poisoning. After death the lead content of the excreta, of the unabsorbed remainder of the deposit at the seat of injection, and the lead content of the bodies of the animals was determined by the gravi- metric sulphate method. Most of the absorbed lead was found in the excreta. The tissues, except those close to the subcutaneous de posit of lead, contained only very small amounts of lead. Although there were several unsatisfactory features in these experiments, nevertheless the deductions. made by Straub and Erlenmeyer sug- gest an explanation for the action of lead within the body.
These experimental animals had been severely poisoned, some- times fatally, during the process of the transportation of lead from the site of injection to the organs where it was later excreted, although at the time of death only very small amounts of lead were found stored in the body. ‘The authors conclude therefore that the toxic effects are due not to deposits of lead at the site of injury but rather to the “lead stream,” that is, to the small concentration of soluble lead which is transported in the circulating blood. They point out that the stream is always small, too small to produce any effect were it a single dose, but that as the transportation and absorption continue, innumerable subminimal attacks bring about pathological changes in certain sensitive tissues, and both time and the concentration of this “lead stream” are important factors in the production of toxic symptoms.
Minot’s experiments were so planned as to compare the rate of absorption of lead which enters the body through the gastro-intes- tinal route with that entering through the respiratory tract, and to follow its fate in the body. Carlson and Woelfel (18) had shown that even those compounds of lead which are considered most in- soluble dissolve to some extent in the gastric juice. Meillére (9) had asserted that the entire gastro-intestinal tract absorbs soluble lead, although in the alkaline medium of the small intestine and with the hydrogen sulphid often present in the colon a large per-
48 INDUSTRIAL POISONS IN THE UNITED STATES
centage of lead is reprecipitated. This portion, together with what escapes solution in the stomach, represents a large part of all the lead that has been ingested, and probably this part never actually enters the organism but is excreted directly in the feces. Some portion, however, is absorbed even from very small doses, and if these are repeated, enough is absorbed to cause poisoning. The distribution in the body of this absorbed lead was the subject of her investiga- tions.
Minot found it possible to produce chronic plumbism in cats with- out acute gastric symptoms by administering every other day a dose of lead acetate solution amounting to 50 mg. per kilo of body weight. The cats died or were killed after varying periods, and the lead distribution in the body was studied. It varied a good deal in the different animals, probably because changes of localization of the lead occur at different stages of poisoning; but in all animals the tissue which held the largest percentage of lead was the skeleton, where sometimes as much as 85 per cent of the total deposit was held. In general, the longer the duration of poisoning the greater the proportion of lead in the skeleton. The amount of lead found was a very small proportion of what had been administered, only 5.8 mg. up to 88.9 mg., although amounts running from 1.0 to 11.4 gm. had been administered, which shows that there is in the body a very efficient mechanism to prevent the absorption of lead. Evi- dence points to the liver as the principal protective mechanism; for when the experiment is shortened, and the animal is killed in the earlier stages, the liver is found to contain a relatively high per- centage of the total lead absorbed, this lead having been brought there in the portal circulation. The fact that the quantity of lead stored in the liver does not increase progressively as absorption con- tinues and that the total amount retained in the body is small, points to extraordinarily efficient excretion by the liver. Minot refers to some unpublished experiments by Brady of Harvard who found that the bile is an important path of excretion for lead.
In gastro-intestinal poisoning, therefore, a large proportion of the lead reaches the comparatively invulnerable region of the intes- tines, liver, and portal circulation. The small amount which escapes excretion in the bile is found chiefly in the bones, which tend to remove it from the blood stream and store it. For example, in the body of a cat which lived for 162 days of experiment, 77.2 per cent of the lead was found in the skeleton; 12.8 per cent, in the muscles; 7.4 per cent, in the liver; 0.6 per cent, in the colon; and the kidneys, lungs and heart had each 0.3 per cent; the stomach, 0.2; and the brain and cord, 0.1.. On the other hand, in a eat killed at the end of 18 days the distribution was quite different,—only 40.9 per cent was found in bone, while the liver contained 21.8 per cent; the muscles, 12.4 per cent; the kidneys, 11.3 per cent;
INDUSTRIAL POISONS IN THE UNITED STATES 49
the stomach, 5.2 per cent; the small intestines, 3.6 per cent; the colon, 2.0 per cent; and the lungs, 1.7 per cent.
The question at once arose as to whether, if absorption should cease, all the lead would become localized and stored in the bones as a temporarily harmless deposit. A series of experiments was therefore carried out to test this point and at the moment when the animals, six cats, were severely poisoned and death seemed immi- nent, the administration of lead was stopped. With no treatment whatever except good care, the cats gradually returned to normal condition, their lost weight was regained within a few weeks, and they seemed well in every way. ‘Two were then killed and their tissues analyzed, and it was found that in spite of the interval of several weeks since.the administration of lead had ceased and in spite of the fact that all symptoms of lead poisoning had dis- appeared and the animals were apparently in a normal condition, a considerable amount of lead was found to be still retained in the body, almost all of it in the skeleton.
DistriputTion oF Leap tn Tissues or Cats Kitiep Sreverat Montus Arrer Last Doses or Leap sy Moutu
Percentage Distribution of
Tatexsal [Total lead sbieerdaate Cat Total lead since last | found in received d sk Gastro- “on Ody |Skeleton| Liver | Kidney | intest. tract gm days mgm. L 1.68 82 20.53 98.5 Lo 00 00 M 11.09 160 97.29 97.0 0.6 1.4 150
The contrast between the harmlessness of the stored lead and the marked toxicity of this same lead when it was in process of absorp- tion and transportation gives confirmation to the theory held by Straub and Erlenmeyer that the damage is done not by the stored lead but by small amounts carried in the blood stream.
All this concerns absorption by the gastro-intestinal channel. When the method of administration is by introducing lead dust into the respiratory tract the result is different. Minot succeeded in administering finely divided lead to animals in such a way as to insure its reaching the lungs. and prevent its being swallowed with the saliva and mucus. The method used was the following:
“With the animal under ether anesthesia, the neck was opened, aseptically, with as little trauma as possible, and the esophagus securely ligated with four strong linen sutures just below the level of the thyroid gland. The wound was then closed and generally required no further attention. While the animal was still anes-
50 INDUSTRIAL POISONS IN THE UNITED STATES
thetized a small glass tube was inserted, through the mouth, into the trachea nearly as far as the bifurcation. From 1 to 5 ce. of a rather heavy suspension of a lead compound in sterile physiological salt solution (p. h. 7.4) was then introduced through this tube. Less post-operative lung infection has been found to follow the alter- native method of injecting the lead suspension through a large needle inserted in the lumen of the exposed trachea. This is probably because bacteria of the mouth are avoided. No leakage occurs, since the elasticity of the tissue completely closes the hole made by the needle. When the lead suspension was in the trachea ‘the cat’s head was held high by elevating the cat-board for a few minutes to facilitate insufflation of the particles by gravity.”
Since the esophagus was closed, a fact always confirmed at au- topsy, there was no possibility of absorption of lead from the gastro- intestinal tract. The duration of the experiment was of course limited to the time that the animals could be kept without food. Fluid, however, was introduced daily by intraperitoneal injection, and the animals were well cared for in artificially warmed cages and showed no discomfort except that of fasting and the drooling caused by the inability to swallow. Seven days was the maximum period of survival after operation. Fifteen animals received lead as carbonate, five as oxid, three as sulphid, and two as chromate. In every instance the amount of lead absorbed after a single ad- ministration was in striking contrast to the much smaller quantities which would be absorbed in the same period after the swallowing of larger doses of dissolved lead. The quantity of lead found in the tissues, 24 to 48 hours after administration through the lungs of 150 to 200 mg. of solid lead carbonate, is as great as after the administration of several grams of lead in solution during weeks of continuous lead feeding. This fact emphasizes again the marked efficiency of the liver in preventing lead from entering the organ- ism. When it is absorbed by the lung lead at once enters the gen- eral circulation, and since only the small portion of blood carried in the hepatic artery goes directly to the liver, the efficient short- circuiting of the lead in the portal circulation of the liver and in the biliary circulation is impossible; instead, all the absorbed lead is distributed by systemic blood.*
Whatever may have been the path of entry, the skeleton always exerts a strong attraction for lead in the blood stream. Because lead absorbed through the lungs enters the general circulation di- rectly, it is more promptly distributed through the organism than that absorbed into the portal blood from the gastro-intestinal tract. This explains the well-known danger of exposure to lead dust in industry. It also explains why the deposit in the skeleton is rela-
*Lead is transported as an insoluble triple phosphate, largely in the blood plasma. See p. 34.
INDUSTRIAL POISONS IN THE UNITED STATES 51
tively greater than after gastro-intestinal absorption of the same duration. In chronic cases following the absorption of lead by either route, the distribution within the body does not differ, and in both modes of absorption there is an almost complete selective localization of lead in the bones.
These experiments have a bearing also on the changes which lead undergoes in the body. A. S. Minot found that after the introduc- tion of lead chromate into the lungs there was a deposit of lead in
. the skeleton but no trace of chromium could be detected even by
the extremely delicate diphenylearbazide test of Cazeneuve. LEvi- dently the chromate has been dissolved and reprecipitated in the form of phosphate. Such solution could be readily effected only at a hydrogen ion concentration considerably higher than that which is generally found in the body, but it has been shown by Jacobs (19) that it is possible, as a result of the penetration of carbonic acid, for a much higher degree of acidity to develop within cells than in the medium surrounding them, and it is conceivable that condi- tions might be produced in the phagocytic cells which would be suitable for the solution of the lead particles engulfed by these cells.
The animals which survived longest in these experiments, more than four days after the operation, always showed a different dis- tribution of the lead throughout the body than was found in those dying more promptly. There was still a large percentage of lead in the skeleton, but as much as 12 to 30 per cent now appeared in the liver and the gastro-intestinal tract, which was in strong con- trast to the small traces found in these tissues in the earlier experi- ments. Minot suggests that the explanation may lie in the fact that the animals were fasting and that the acidosis of starvation may hasten the mobilization and excretion of the stored lead.
Aub and Minot (3) found in cases of human lead poisoning that clinical treatment based on this theory would result in increased excretion of lead. Their first report deals with eleven cases of plumbism in men, chiefly chronic plumbism. These patients were at the time excreting no lead, and in some instances there had been no exposure to lead for several weeks. The administration of phos- phorie acid was followed by the appearance of lead in urine and feces, and the same was true, but to a much less marked degree, of lactic acid, while potassium iodid had a much slighter effect. In one case of colic with excretion of lead, the administration of magnesium sulphate was followed by a fall in the excretion of lead, while phosphoric acid increased it. A summary of the results obtained showed that more than four times as much lead was excreted in stools and urine under phosphoric-lactic acid treatment than before. The largest amount obtained in 24 hours was 6 mg. The findings of six autopsies bore out the animal experiments and showed that in
52 INDUSTRIAL POISONS IN THE UNITED STATES
human beings also the skeleton is the place where lead is chiefly deposited.
Aub points out the bearing of these experiments on medico-legal problems. If examination of the organs of a person dying of sus- pected plumbism fails to reveal lead this must not be taken as negative proof, for the bones of the skeleton may be full of lead. On the other hand, the finding of lead in the bones does not prove that lead was the cause of death unless there were clinical symptonis of lead poisoning, in which case it is a valuable confirmatory sign. -
Another very interesting series of experiments designed to throw light on the mechanism of poisoning by lead dust were published recently by Blumgart (20) of Harvard. He had found that pitui- trin could not be absorbed from the mouth, the rectum, or the stomach, but would be taken up from the nasal mucosa. He there- fore undertook to see if particulate matter, such as white lead, could be absorbed in this way. ‘The nasal passages are not only well adapted to catch and hold such particles, but because of their un- usually rich blood supply and the close meshwork of submucosal lymphatics they seem well adapted to absorb soluble dust, and per- haps the abundant supply of mucus may exert a solvent effect on the lead salts.
Blumgart used dogs and cats and prevented absorption through any other surface than the nasal by occluding the trachea and esophagus. That this was effectual he was able to prove by subse- quent search for lead in the organs below the ligatures, which search never revealed more lead than was to be expected from the usual — distribution found by Minot. He then sprayed powdered white lead into the nose with an ordinary nasal atomizer. The animals survived the operation for only 16 to 36 hours. He gives the result of analyses in four animals, using for quantitative estimation Fair- hall’s method. Lead was found in the skeleton in the following amounts: No. 1, 7.5 mg. metallic lead; No. 2, 22.3 mg.; No. 8, 29.8 mg.; No. 4, 28.3 mg. The liver contained from 0.1 mg. to 1.3 mg.; the internal organs from 0.2 to 0.8 mg.; and the muscles from a faint trace to 0.3 mg.
The lead found in these experiments, averaging 22 mg. of metallic lead, is far in excess of the minimal toxic dose for these animals. It must have been absorbed from the upper respiratory passages and proof is therefore given that here there is a place of ready absorption for white lead dust, at least in cats and dogs. If this be true of animals it must be still truer of man, for it is well known that the natural protection of the human nose against dust is far less efficient than that of the dog’s nose or the cat’s.
The studies made by Aub and his colleagues furnish an explan- ation for those cases in the literature of what has been called latent plumbism in which under various conditions, sometimes an acci-
INDUSTRIAL POISONS IN THE UNITED STATES 53.
dental injury or an acute illness, sometimes the administration of potassium iodid, the symptoms of lead poisoning appear after a more or less prolonged period of freedom from exposure to lead, or which continue to excrete lead for long periods after the exposure to lead has ceased. ‘Tanquerel described the case of a man who had repeated attacks after several years’ absence from lead work. Oliver has reported several instances. One was in a woman who suffered from colic and double wrist drop. She gave up work with lead, and two or three weeks later was admitted to the hospital under another physician, this time suffering from aortic aneurism. She was given fairly large doses of potassium iodid, and within two weeks she had developed a deep blue line on the gums and a double wrist drop and she became rapidly emaciated and died, not from the aneurism, but from the lead. Oliver also reported at the Brussels Congress, in 1910, the case of a painter with double wrist drop in whose urine Bedson found considerable quantities of lead more than a year after the man had quit work. Oliver’s most often quoted case of latent plumbism was in a woman who, when 19 years old, suffered from lead colic, blindness and paralysis, left work, recovered, married, and had several children. Seventeen years later, without having done any lead work during this interval, she had an attack of headache and ocular paralysis with diplopia, and was found to be eliminating lead in the urine. W. Gilman Thompson (21) also reports the case of a woman who had a marked lead line on the gums, stippling of the red blood cells, abdominal colic, and partial wrist drop, after an interval of five years free from exposure to lead. She had had a double wrist drop before.
I found a lead worker in the Cook County Hospital in Chicago suffering with typical colic and constipation lasting five days, and with stippling of the red cells. This was his third attack and came on ten months after he had last been in contact with lead. His second attack followed eight months’ freedom from exposure to lead. Among the cases of encephalopathy described in Chapter 6 are those of two smelter workers from the ore hearth plants in southwestern Illinois, who developed encephalopathy several months after they had left the smelter. Teleky describes a case seen by Frankl-Hochwart in which latent plumbism became active after a fracture of the thigh. The patient, a woman fringe-knotter, worked for years handling silk thread which was weighted by means of lead. After her accident she developed a paresis of the radial and ulnar nerves.
Larzell’s (22) case was in a man who while working as a foreman in a sheet lead works had so severe a colic that he almost died and was forced to give up his position. or sixteen years he had no contact with lead, but he was never as strong as before and suffered
54 INDUSTRIAL POISONS IN THE UNITED STATES
more or less from “rheumatism.” Three months before Larzell saw him he had lobar pneumonia and as the lung was slow in clear- ing up his physician gave him iodid of potassium, whereupon a typical foot drop developed.
An interesting side-light on the effect of changes in metabolism on the absorption of stored lead is furnished by Shufflebotham (23), in an article on the influence of military training on certain mem- bers of the British Expeditionary Force who came from North Staffordshire. In this contingent, between August, 1914, and the early spring of 1915, fourteen cases of lead poisoning developed, with anemia, constipation, headache, nausea, colic in twelve, neuritis of the arms in one. The men were all lead workers, ten of them potters, three painters, one a plumber. Only three had ever had such an attack before and in all the onset came on in three to seven weeks after the beginning of military training. Shufilebotham be- lieves that the drilling increased metabolism and released com- pounds previously locked up in the organs and muscles.
BIBLIOGRAPHY
(1) nes» P. O. Miinch. med. Wehnschr., 1918, 65, 1407.
(2) Brezine, E., and Eveuinc, M. Wien. Arb. a. d. Geb. d. soz. Med., 1912, V, 29.
(3) Publications of the Harvard Lead Group, 1922-23 (J. C. Aub, L. T. Fairhall, A. S. Minot, J. A. Key, Paul Reznikoff, D. E. ‘Smith, and H. L. Blumgart), are for the most part still in press but will appear shortly in the form of a monograph, the separate articles of which will appear in forthcoming numbers of the Journal of Experimental Medicine, the Journal of the American Chemical Society, and the Journal of Biological Chemistry.
(4) Breton. Les maladies professionelles, Paris, 1911, p. 154.
(5) Outver, T. Lead Poisoning, London, 1914, p. 6.
(6) LeacEe and Goapsy. Lead Poisoning and Lead Absorption, New York, 1912, p. 174.
(7) Goapsy, K. W. “A Note on Experimental Lead Poisoning,” J. Hyg., 1909, 9, 122.
(8) Miuer, R. Die Bekimpfung der Bleigefahr in Bleihiitten, Jena, 1908.
(9) Memuire, G. Le saturnisme, 1903, Paris.
(10) Lenmann, K. B. Saito, Y. and Gfrori, W., Arch. f. Hyg., 1912, 75, pp. 134, 152, 160.
(11) Goapsy, K. W. and Goopsopy, F. W. “A Note on the Pathology of Lead Poisoning,” Lancet, 1909, 2, 990,
(12) Srieciirz. ‘Hine experimentelle Untersuchung iiber Bleivergiftung,” Arch. f. Psychiat., 1892, 24, 1.
(18) Rorn. “Ueber Bleistaub und Bleidimpfe,” Beitr. z. path. Anat. u. z. allg. Path., 1905, 7, suppl. 184.
(14) Buum, F. “Medizinisches iiber die Bleivergiftung,” Deutsch. med. Wchnschr., 1912, 88, 645; also Wien. med. Wehnschr., 1904, 54, 538.
(15) FAatrHALL, 24 ad “Lead Studies, ” T. “The Estimation of Minute Amounts of Lead in Biological Material,” J. Ind. Hyg., 1922, 4, 9-20.
INDUSTRIAL POISONS IN THE UNITED STATES 55—
(16) Srraus, W. “Ueber chronische Vergiftungen, speziell die chronische Bleivergiftung,’ Deutsch. med. Wchnschr., 1911, 37, 1469; also “Gift und Krankheit nach Beobachtungen an experimentellen chronischen Bleivergiftung,’ Miinch. med. Wchnschr., 1914, 61, 5.
(17) Ertenmeyer, E. “Ueber den Mechanismus chronischer Bleivergif- tung,” Ztschr. f. exper. Path. u. Therap., 19138, 14, 310.
(18) Carutson, A. J., and Worxrer, A. “The Solubility of White Lead in Human Gastric Juice and its Bearing on the Hygiene of the Lead Industries,” Am. J. Pub. Health, 1918, 3, 755; also J. Phar- macol. and Exper. Therap., 1918-14, 5, 549.
(19) Jacops. Quoted by Minot.
(20) Buumeart, H. L. “Lead Studies, VI.” “The Absorption of Lead from the Nasopharynx,” J. Ind. Hyg., 1923, 5, 153.
(21) THompson, W. Girman. The Occupational Diseases, New York, 1914.
(22) Larzett, E. W. Colorado Med., 1910, 7, 348.
(23) SHurriesoTtHaM, F. “The Effects of Military Training upon Lead Workers,” Brit. M. J., 1915, 1, 672-704.
QUANTITY ©
Various data have been used in the effort to calculate the amount of lead which, ingested daily over a long period, may be capable of causing plumbism. Facts have been gathered with regard to sev- eral mass poisonings from drinking contaminated water, the most famous instance of which occurred at the Chateau de Claremont, where out of 24 persons 13 were poisoned in a short time by drinking water with about 65 mg. of lead to four liters, or 16.5 mg. per liter. More interesting, because more insidious and long drawn out, was the poisoning of nuns in a convent near Lyons which was discovered by Lacour after three had died and when twelve were still living and seriously affected with anemia, palsies, colic, and one had progressive paralysis and muscular atrophy. These nuns had drunk only water for years. The water was found to contain 2.7 mg. per liter and inquiry showed that there had been a change in the water supply ten years before which led to this contamination. All of the nuns in the convent were poisoned except two who had been there for only five months and one year, respectively.
An interesting account of self-experimentation in lead poisoning is to be found in early American medical literature. A young physician, Thomas R. P. Spence, of Accomac County, Virginia, on July 23rd, 1805, wrote a letter to John Redmond Coxe, M.D., the editor of the Philadelphia Medical Museum, which was published in the second volume of the 1806 issue. Spence tells of his personal experience with the use of sugar of lead in epilepsy. He had had epileptic seizures since his 23d year, that is, for the two previous years. He had treated himself unsuccessfully with bleeding until he was considerably reduced in weight, and then with cuprum ammoniacum, but at every full moon and change of the moon he would be subject to fullness in the head or headaches. Following
56 INDUSTRIAL POISONS IN THE UNITED STATES
the advice of Doctors Rush, Wistar, and Church, of Philadelphia, he continued the above treatment and also took mercury, zine, and lead. ‘The mercury had a good effect provided he kept up a con- siderable ptyalism, which he did for seven months with two attacks of actual salivation. Bleeding was practiced regularly once a month. He had only four fits between May 27th and December 4th. By September he was so much reduced by this regimen that he left it off for cold shower baths, but he had two attacks and resumed the mercury. Dr. Rush then told him that he had good results in children with sugar of lead, though he had had little success with it in adults. Spence began to take it in quarter grain doses three times a day, increasing in one week to one grain, then after two more weeks to eight grains twice a day, and he continued this for three or four weeks, with “happy effect on the fits.” He de- scribes his condition at the end as follows: Costiveness, sponginess of gums with dark livid appearance around the incisors, fetid breath, mouth not sore although teeth were loose, a much greater increase of urine than under mercury, painful motion in the joints of the upper extremities, especially the elbows. He was then bled sixteen ounces and the following day lost accidentally eleven ounces more, whereupon his appetite left him and he went for three or four days with no food at all. Pain in the epigastrium then devel- oped, extending down below the navel and also in the region of the liver and in the spine. This became excruciating and lasted for ten days. Less severe, but distinct, pain continued for six weeks, extending to the legs so that he could not stand. He had a slow convalescence, but for seven months he was quite free from epileptic fits. He hazards the suggestion that the good effect of the lead came from its “contracting the stomach and thereby pre- venting plethora”; for after this attack of colic he could never eat much without a sense of fullness in the stomach.
Schmidt (1) had the opportunity to study a case of slow poison- ing which developed after years of drinking water with a relatively large amount of lead and he believes that the danger from this source has been exaggerated. His patient drank daily two and a half liters (!) of water containing 2.9 mg. of lead per liter, which means a daily dose of 7.25 mg.; yet it was two years before she felt the first symptoms of illness and two and a half years more be- fore Schmidt saw her in a condition of pronounced plumbism, with colics, palsies, cachexia and a lead line. Schmidt estimates that she had had 5.3 gm. before the effect was felt at all and 12.6 gm. before the lead had done its full work. :
Brouardel (2) used to emphasize in his lectures on industrial plumbism the importance of time in the production of lead poison- ing. He said that in the middle of the last century it was customary to treat dysentery with carbonate of lead and that in the hospital
INDUSTRIAL POISONS IN THE UNITED STATES 57
of La Pitié he saw 300 or even 800 mg. given for several days with- out any bad reaction; yet if the same patient should absorb 800 mg. in one year instead of in eight days, he would get lead palsy. “One must not conclude that the gravity of the danger depends on the size of the dose. I would almost say, with a little exaggeration, perhaps, that the reverse is true.”” He believed that the daily inges- tion of as much as one centigram will cause poisoning. Teleky (3), puts the amount at a lower figure. A daily dose of anything over one milligram for several months may lead to symptoms of plumbism, while Brouardel’s dose, one centigram, would produce acute symptoms in a few weeks.
The most satisfactory calculations for those interested in indus- trial plumbism are Legge’s (4), based on analyses made by Duck- ering of the lead content of the air in certain workshops—potteries, tinning shops, painting coaches, and railway cars, ete. Taking these figures of Duckering’s (5), and the records of plumbism among the employees of the given establishments, the length of exposure and the character of the plumbism that appears among them, he is able to make a fairly exact statement of the quantity of lead which is to be regarded as dangerous. He concludes that two milligrams per day is the lowest dose which, when inhaled as dust or fumes, may, in the course of years, set up lead poisoning. If the working day is eight hours—as it almost always is in British industry—this would mean about 5 mg. of lead to 10 cubic meters of air; for a man breathes about 600 cubic centimeters 16 times a minute, or 4,608 liters in eight hours. If there is no more lead in the air than this, encephalopathies and palsies will not occur, and colics rarely.
BrIsBiioGRAPHY
(1) Scumir, P. “Ueber die Bedeutung der Blutuntersuchung fiir die Diagnose der Bleivergiftung,” Zentralbl. f. Gewerbehyg., 1914, 2, 8-11.
(2) Brovarper, P. “L’intoxication saturnine causée par les aliments; modes d’absorption et d’élimination du plomb,’ Med. mod., 1904, 15, 25-27.
(83) Tetexy. See (4).
(4) ear In Legge and Goadby, Lead Poisoning and Lead Absorption, 207.
(5) Ducxertnc, G. E. “Methods of Determination of Dust and Lead in an Air of Workrooms,” Ann. Rept. Chief Inspector Factories, 1910, 01.
CHAPTER 4 COLIC. ARTHRITIS Coxic
Lead Colic.—The clinical course of a typical case of lead colic begins with more or less obstinate constipation which increases and culminates’ in an attack of intense, agonizing pain. This. is usually spasmodic and during a paroxysm the exploring finger in the rectum can often detect alternations of violent contractions and slight relaxations. It is on this fact that the therapeutic use of belladonna, hyoscyamus and opium is based. ‘The pain may be great enough to cause collapse, even delirium, with evidence of great suffering. -In the early days (before 1912), it was not difficult to secure histories of white lead workers who had been picked up in the street by the police, helpless with lead colic. Sometimes there is no warning at all before an attack, but usually it is preceded by several: days of discomfort, if not of pain. An Italian, employed in a Chicago white lead works, was seized with a pain so sudden and severe that he thought someone must have struck him in the abdomen, and he had no feeling of illness before.
The pain is referred to the umbilical region, and the patient doubles up or falls to the ground, pressing both hands over his rigid, retracted abdomen. In bed he is likely to lie on his face ana pressure usually relieves the pain, except in neurasthenics, who often complain of exquisite tenderness over the abdomen, a symp- tom which may obscure the diagnosis; for many lead workers are neurasthenic. ‘The pulse is decidedly slowed, small, with increased tension; the blood pressure during the paroxysm is raised, but falls as the pain dies down. ‘There may be complete suppression of urine during the attack and the first urine passed after it may contain urobilin, hematoporphyrin, and even albumin and casts. The respirations are rapid and labored. Constipation is a marked feature in all but exceptional cases, about 3 per cent; nausea is common; actual vomiting, not so common; thirst is a very charac- teristic feature, as is the absence of sweat, even during the most agonizing pain; and there is a striking pallor from contraction of the surface vessels of the face. In France, Bernard (1) and others have distinguished a form of lead colic characterized by paralysis of the intestines and by meteorism, instead of by contractions, and Walko (2) says that the intestinal musculature in lead colic may be actually atonic. Finally there may be lancinating pains in the
58
INDUSTRIAL POISONS IN THE UNITED STATES 59
limbs. ‘The duration of this acute stage is usually more than twenty-four hours, although in light cases it may last only a few hours. There may be recurring attacks of intense pain with remissions for more than a week.
Walko studied the course of 43 cases of acute gastric plumbism in a hospital in Prague. He concludes that functional disturbances of the stomach appear very early in the course of poisoning, severe symptoms occurring after three or four weeks’ exposure in men working in lead dust. There is a reduction or stoppage of acid and of secretion ferments, and a disturbance of the motility of the stomach, which last is at first greatly exaggerated, then reduced. The symptoms first observed are loss of appetite, metallic taste, nausea, vomiting, constipation, pain in the region of the umbilicus, which was typical colic in only one-third of the cases. The gastric juice collected after a test meal is small in quantity, lacking acid and ferments, although pro-ferments are present in all but very severe cases. The pain and disturbed digestion are probably caused by pyloric spasm, but later on there is atony of the gastric walls. In several cases carcinoma of the stomach was suspected, because of the presence of blood and lactic acid in the stomach contents and the profound anemia and cachexia. In others, the picture was that of gastritis anacida, or mucosa. The diagnosis was made by the rapid onset of the disease in a previously healthy man, the history of occupation, and the discovery of a lead line and of stippled red cells.
BIBLIOGRAPHY
(1) Bernarp, H. Thése de Paris, 1901. (2) Watxo, K. “Die Erkrankungen des Magens bei der chronischen Bleivergiftung,” Miinchen. med. Wchnschr., 1907, 54, 1728.
ARTHRITIS
Arthralgia is one of the four manifestations of plumbism de- scribed by Tanquerel (1), the other three being colic, palsy, and encephalopathy. In his cases, it was next to colic the most com- mon form, occurring in 755, and in 201 cases it was the only symptom; in the others it was associated with one or more of the other three forms. Usually a man susceptible to colic is also suscep- tible to arthralgia, but red lead makers—roasting oxids in the furnace—are more susceptible to arthralgia than to colic. In 463 cases of lead poisoning in red lead men, 400 had arthralgia, 63 colic. The prodromata of arthralgia are usually numbness and lassitude in the limbs: in 205 of the 755 cases, colic preceded an attack; in five, palsy; and in one, encephalopathy. The attack is very likely to come on at night, is most often localized in the legs, then in ' the arms and shoulders, then in chest walls, back and head.
60 INDUSTRIAL POISONS IN THE UNITED STATES
These are Tanquerel’s figures: 485, lower limbs only; 88 upper limbs; 108 upper and lower; 35 upper, lower and trunk; 18 thighs; 9 head; 5 chest walls; 4 back or neck; 3 head. [Pain is most often “in the course of flexion,” 7.e., along the posterior aspect of the thigh, the calf of the leg, and the sole of the foot, the arm-pit, anterior arm, fold of the elbow, palms of the hands. The pain affects the larger joints; the small usually escape. The pain is most often in the lumbar region of the back. It may be described as like a painful electric shock, or boring, or stabbing. Paresthe- sias, formication, numbness, and cold or heat may accompany it. It comes on in paroxysms which may be started by cold or by motion. Slow, gentle pressure relieves the pain; deep pressure increases it. The muscles cramp and may be felt and sometimes even seen as hard balls. There may be no heat or swelling and the pain does not follow the whole course of a nerve trunk. In 75 per cent of Tanquerel’s cases the pain was bilateral, but not equal on the two sides. ‘The rapid amelioration under treatment helps in the diagnosis; other aids are the fact that pressure and motion are not as painful as in articular rheumatism, and that in neuralgia the pain and tenderness are felt along the whole nerve trunk and with recovery the whole trunk is clear, while lead arthralgia clears up in sections.
Less stress is laid on arthritic symptoms by modern writers than by Tanquerel, yet this form of saturnism is recognized if not care- fully studied. “Rheumatic pains,” myalgia, arthralgia, are noted as aiding in a diagnosis of lead poisoning in dubious cases. (See page 103.) The pain may be as cramping as colic. It is relieved by gentle pressure, and a serious disabling attack does not usually last more than a week, but may recur many times.
A Negro, 22 years old, employed in a small Chicago refinery, _stirring, skimming, and pouring lead for something less than six months, was awakened one night with cramps in his legs, “jumping from leg to leg,” then spreading to all the muscles of the body, but never in all at once. He could feel his muscles contract into hard knots. Colic followed this. Another Negro, a white lead worker, complained of a “slow, aching pain” down his right leg from the hip to the ankle and from the left hip to the knee, on the posterior aspect of the limb. In the upper part of both arms he felt an acute, sharp pain and the right shoulder was very painful on movement, the right forearm sore to the touch, and the middle and ring fingers dropped slightly on extension.
That lead can set up true gout was first asserted by Garrod (2), in 1854. Striimpell (3) (1911 edition) says that he has often seen lead gout in Erlangen and in Leipzig, but always in men, such as painters and compositors, who had been exposed for many years to slow poisoning. Liithje (4), whose article is always quoted
INDUSTRIAL POISONS IN THE UNITED STATES 61
in this connection, asserts that lead can set up true gout, and that the distinguishing features of this form of gout are the following: the youth of the victims, the rapid spread of the disease, the in- volvement of joints spared in ordinary gout, the great tendency to formation of tophi. According to Striimpell, the prognosis of saturnine gout is poor.
Garrod said that one-fourth of all the cases of gout in England were to be found in lead workers, but Oliver (5) found lead gout rare in the north of England. In the experience of the Johns Hopkins Hospital for twelve years, one-half of the lead cases were associated with gout (W. Gilman Thompson). Thompson (6), himself, saw only five out of sixty-four cases of plumbism associated with gout.
BrIsiioGRAPHY
(1) Tanqueret, L. Lead Diseases, a treatise from the French of L. Tan- querel des Planches, trans. by Samuel L. Dana of Lowell, 1850.
(2) Garrop. See Allbutt, Clifford, The Oxford Medicine, Oxford Press, 1921, vol. 4, p. 80.
(3) Srriimpenn, A. A Text Book of Medicine for Students and Practi- tioners, New York, 1911.
(4) Livrugse. “Bleigicht und Harnsiure Ausscheidung,” Ztschr. f. klin. Med., 29, 1896.
(5) Oxiver, T. Diseases of Occupation, London, 1916, 210.
(6) THOMPson, W. Guman. The Occupational Diseases, New York, 1914, 258.
CHAPTER 5 LEAD PALSY
Tue palsy of lead poisoning is a progressive muscular atrophy, toxic amyotrophy, which may be of the pure atrophic type, usually localized and of slow development, rarely generalized, and rapidly progressive; or it may belong to the spastic, atrophic type of Charcot’s amyotrophic lateral sclerosis (1). Five varieties are generally recognized, following the classification introduced by Mme. Dejerine-Klumpke (2).
First is.the antibrachial type which involves the extensors of the wrist and fingers, with the supinator escaping. Second is the brachial type which involves the deltoid, biceps, brachialis anticus, and the long supinator; and this is sometimes called the scapulo- humeral form and may be primary or may follow the antibrachial. Third is the Aran-Duchenne type of amyotrophy, 2¢., a more or less rapid atrophy of the small muscles of the hand which begins in the thenar eminence, then involves the interosseous and hypoth- enar muscles with flattening of the hand, the “main de singe,” and then, as atrophy progresses and the middle and nail fingers flex, the “main en griffe” results. The fourth type is the peroneal, which, according to Tanquerel, is the type seen in 13 cases to 100 cases of type one. This type of palsy attacks the extensors of the toes, the peroneal muscles, and sometimes the tibialis anticus; more- over it is also bilateral, symmetrical, and is attended with loss of tendinous reflexes. The fifth is the very rare laryngeal type de- scribed by Seiffert in 1884 and later by Morell Mackenzie, Stieglitz, de Schweinitz, and others.
The first is by far the most common type and is the one usually meant when the term lead palsy is used without qualification. In typical lead palsy the common extensor of the fingers is first at- tacked and when an attempt is made to extend the fingers, the middle and fourth having no extensor of their own, remain flexed. In the early stage, the man cannot with extended fingers flex the hand dorsally (or extend the wrist), and if he tries to do so the first phalanges of the fingers begin to bend. The same thing occurs if passive flexion is attempted with the hand supported; for the weakened extensors are not able to keep the fingers extended against the pull of the interosseous and lumbrical muscles which are not affected. On the other hand, if the patient doubles up his fist or
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INDUSTRIAL POISONS IN THE UNITED STATES 63
even flexes the fingers half way, the hand can be flexed dorsally (the wrist can be extended*). Gowers (3) explained that if the fingers are extended, dorsal flexion of the hand (extension of the wrist) must be accomplished by the long extensor of the fingers acting. alone—and in typical lead palsy this is the very muscle affected,—but if the fingers are flexed, dorsal flexion of the hand is brought about by the action of the true wrist extensors. This test reveals a very early stage of palsy of the long finger extensors. With extended wrist (hand dorsally flexed), the fingers will flex, the two weakest, the middle and ring fingers, showing the effect most, the index least.
This is the ‘“antibrachial type” of Dejerine-Klumpke, Remak’s (4) “forearm type.” The palsy is always symmetrical, although usually unequal in degree on the two sides. In right-handed men the right hand suffers most, in left-handed, the left. Injury to other muscles follows more or less rapidly. ‘The extensors of the index, the little finger and the wrist may be affected, as are some- times the triceps, and sometimes the biceps; hut the long supinator usually escapes. As the interosseous muscles are supplied by the ulnar nerve they are not affected, the fingers can be approached, and if the basal phalanges are supported, the fingers can sometimes be extended. A characteristic feature is the relatively slight involve- ment of the thenar muscles and the escape of the interossei. The osteotendinous reflexes are abolished in the upper extremity. Elec- trical excitation of the palsied muscles shows functional disturb- ance; faradic irritability is impaired or lost; galvanic, less im- paired; and very rarely there -is a reaction of . degeneration.+ Atrophy appears early, especially in the muscles of the back of the forearm.
The curious localization of the lead palsies, especially the typical form known as painters’ palsy which involves some but not all of the muscles supplied by the radial nerve, has interested pathologists for many years. In 1904, Edinger (6) promulgated his theory as to the localization of lead palsies, and in 1908 brought it out in more complete form. It is an application to lead poisoning of the reasoning by which he sought to account for the localization of the lesions in tabes. As Edinger himself recognized, others had already connected localization of lead palsy with over-use of certain muscles because of the perfectly obvious fact that the palsied mus-
cles were usually functionally related, although supplied by different nerves. Remak in 1875, Moebius (7), in 1886, and Vierordt (8), - in 1887, had all noted these facts. Kdinger studied chiefly painters’
* It must be remembered that the wrist extensors cause dorsal flexion of the
_ hand; the flexors, volar flexion.
+ Teleky (5) saw one case of greatly exaggerated patellar reflex and spastic
gait. He also saw patellar clonus in another case.
PM
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palsy, the typical form of lead palsy because the most widespread. Teleky (5), in the following year, added a very interesting con- tribution to Edinger’s thesis, with an analysis of many cases of atypically localized palsies in men and women engaged in various occupations, making a close study of the motions required by the occupation and of the exact muscles involved in the palsy. He confirms Edinger’s exhaustion theory unqualifiedly.
The following is a brief statement, condensed from the long discussions of these two authors, of the underlying reasons for the peculiar grouping of affected muscles in various forms of lead palsy, especially in that known as painters’ palsy.
Typical painters’ palsy is an involvement of the long extensor muscles of fingers and wrist with escape of the supinator (brachio- radialis), and sometimes involvement of the long extensor of the thumb with escape of the long abductor, and rarely involvement of the thenar muscles of the hand. It is, therefore, a palsy of certain muscles supplied by the radial nerve, but not of the supinator, and usually not of the long abductor of the thumb. The localiza- tion is founded on function and not on a primary neuritis.
All fine work and heavy work which requires exactness makes demands on a high functional activity of the long extensors of the ~ fingers, the extensors of the wrist, and the small muscles of fingers and thumb. The human arm, with its powerful musculature of elbow and powerful supinators, is formed for heavy, rough work, such as lifting, dragging, carrying; while the wrist and finger ex- tensors are built to perform only the slight activity required of them in heavy work, and yet in all fine work they are the ones most called upon. Lead workers while sometimes engaged in coarse work must do fine work from time to time, and the majority of them, painters, printers, potters, molders, lead burners, plumbers, ete., do work of more or less precision all the time.
Teleky quotes the physiologists, Duchenne and DuBois-Reymond, to the effect that the power of muscles bears a direct relation to their bulk. Now the muscles of the forearm which have the greatest bulk and the greatest capacity for work (“Leistungsfihigkeit’’), are the flexors and extensors of the arm, the supinators, and the flexors of the fingers. ‘There is very little power in the long extensors of the fingers, which are no more bulky than the pronators and the intrinsic muscles of the hand, and which, in addition, suffer from the disadvantage of widely separated attachments. In the thumb the long abductor and the flexors are the most powerful; but as the thenar muscles have opposing functions, the difference between . groups in the thumb is somewhat equalized and is not so great as in the fingers. In doing fine work the hand is always in prona- tion, never supinated, and the extensors of the wrist must be con- stantly used to overcome gravity, to hold the hand up, the flexed
INDUSTRIAL POISONS IN THE UNITED STATES 65
hand being able to do little work because the flexors of the fingers can work properly only when the wrist is dorsally extended. The extensors of the wrist are therefore called into use to help the most powerful and most continually used muscles, the long flexors of the fingers. ‘The flexors of the wrist are called into use, not in fine work, but in heavy work such as lifting, pulling, carrying, with the hand in full supination. ‘Therefore, in fine work the activity of the extensors of the wrist is much more constant and exhausting than that of the flexors, and to this is added their task of overcoming the pull from the finger flexors; for when the fingers are flexed around some object, a paint brush or a tool which pre- vents further flexion, the pull of the finger flexors is exerted on the wrist joint and must be overcome. The long extensors of the fingers do act also as extensors of the wrist, but only by exerting force on the extended fingers, so that they cannot help much when an increased demand is made on the extensors of the wrist, and such a demand is constantly made in fine work.
When the hand is at rest the intrinsic muscles of the hand, the interossei and lumbricales, hold the first phalanges of the fingers a little flexed, overcoming the long extensors; while their extensor action on the middle and nail phalanges is overcome by the flexors, and they also hang a little flexed, the index and fifth finger less than the other two. Slight flexion seems to express normal muscle tonus, and the extensors’ function seems to be to equalize the effect of the flexors.
Throughout the ages man has had to perform chiefly coarse heavy work, such as lifting, carrying, pulling, and heaving, and his mus- cular system is adapted to this. Such work calls upon the long finger flexors, the flexors of the arm and the supinators, in grasp- ing, while the extensors have little to do. In fine work, on the other hand, the extensors are in continual use to offset the flexors and to adjust the finger movements, and they, with the small mus- cles of the hand, have only about one-quarter of the bulk of the flexors. The intrinsic muscles suffer less than the extensors from overuse, because, being shorter, their physical relation to their points of attachment is much more favorable. Old people who have led hard working lives always have their fingers in flexion, but this is not true of the old in the leisure class or in the class of skilled workers.
In typical lead palsy, therefore, the involvement of the long wrist and finger extensors is explained by their relative slenderness, their intrinsic weakness, and their relative over-use, while the escape of the supinator, innervated by the same radial nerve, is explained by _its bulk and strength and the fact that functionally it belongs with the flexors and is not over-used in fine work. The escape of the small muscles of the hand or their late involvement is explained on the ground of their favorable position with reference to their
:
66 INDUSTRIAL POISONS IN THE UNITED STATES
attachments and by the fact that they work partly in conjunction with the powerful flexors. The long flexor of the thumb is bulky and is not affected. The extensor, although it is feeble, is little if at all affected because it is helped by the powerful abductor; while the thenar muscles are affected by fine work because such work calls upon the opponens and the short flexor and short abductor. The extensors of the fingers suffer more than those of the wrists, but the index is not involved as much as the other fingers unless it has had to work harder than they; for it is stronger. The little finger, especially on the left hand, is also less affected, not because it is strong, but because it is so little used. In all advanced cases of this form of lead palsy the right thumb is involved less often than the left. Atrophy of the interossei is rare and usually involves only the first interosseous space.*
Mellon (9), in Warthin’s laboratory at Ann Arbor, undertook to test the validity of Edinger’s exhaustion theory. He worked on frogs because they are convenient for stimulation and the results of fatigue can be computed in a mechanical way. He used lead acetate in water and by stimulating the muscles indirectly, through electrical irritation of skin, he avoided direct injury to the muscle substance. He concluded that if small doses of lead are used by this method, one can obtain conclusive evidence of the validity of the “Aufbrauchtheorie,” namely that fatigue is the main factor in the localization of lead palsy.
Moebius first pointed out the peculiar localization of the palsy in file makers, a finding which was confirmed even by his opponent, Bernhardt (10), although it is not as invariable or uncomplicated
as he thought. The file cutter uses the hammer with his right hand and holds the chisel grasped firmly in his left, striking the metal which is embedded in a lump of lead. The muscles most affected by palsy are those of the left thumb, used in grasping the chisel. Teleky saw a similar kind of palsy in two women who polished lead stoppers for bottles, a complete palsy of the short adductor of the thumb, the opponens, and the outer bundle of the short flexor, partial paralysis of the finger extensors, of the long abductor of the thumb and of the short abductor. The work in- volved the use of the opposing and adducting muscles of the thumb.
Other striking instances of involvement of isolated muscles have been published. Thus, Lilienfeld (11) described a case of pure ulnar nerve palsy in a type polisher who drew the type over a file with a motion always toward the ulnar side. Teleky has seen palsy
* Ingenious and satisfactory as this theory seems to be, it still remains to be explained why fatigue should determine the localization of lead palsy and not of other toxie palsies which occur in industry, such, for instance, as the polyneu- ritis of arsenical poisoning, if the effect of lead is exerted on the spinal cord
and nerve trunks. The idea that the muscle is the real seat of the degenerative action of lead will not down, in spite of all the arguments brought against it.
INDUSTRIAL POISONS IN THE UNITED STATES 67
involving the index finger chiefly in a type finisher who held the individual letters between index and thumb while filing them smooth. Manouvrier (12) saw isolated palsy of the fourth and fifth fingers in a man who pressed lead capsules over the tops of bottles, always making the final pressure with these two fingers. Another interesting instance of curiously localized palsy is given by Teleky. A painter had partial palsy of the finger and hand extensors, inability to lift the arm, and difficulty in rotating it,— in other words, palsy of the lifters, the deltoid (axillary nerve), the supraspinatus (suprascapular nerve), the teres minor (axillary nerve), subscapular and teres major (subscapular nerve), and of the rotator of the shoulder, the serratus (long thoracic nerve). This is a striking instance of the grouping of muscles by function, and not by innervation. The man had been painting machinery with red lead and had had to lie on his back on the floor and paint over his head. His shoulder symptoms cleared up before the ex- tensor palsy, and when he went back to his usual work the extensor palsy increased, but he had no further trouble with the shoulder muscles.
When the work performed is less precise and more varied, the localization of the palsy is more widespread. In glost kilnmen, Teleky found involvement of the upper arm, the thumbs, the supinators, and the tibialis anticus, and he says that Remak noted a similar grouping in potters. I found that the glost kilmmen in American potteries, whose work requires them to lift heavy saggers filled with glazed ware and to place them in the kilns, did not often suffer from wrist palsy but from palsy of the shoulders, which they called being “shoulder bound.” Labbé (13) found two men with acute lead colic, anemia, and palsy, with atrophy of the muscles of the shoulders. They had been working in an electric accumulator (storage battery) factory, rubbing litharge paste into lead grids. Even painters may have involvement of the shoulder muscles. Teleky saw this in three out of fourteen cases of painters’ palsy, and Edinger said that next to the muscles of the wrist and fingers those of the shoulders were most used in painting.
Bernhardt, in Nothnagel’s Handbook, says that disease of the axillary nerve with palsy and atrophy of the deltoid muscle, pro- ducing inability to lift the arm, is sometimes seen as an isolated phenomenon in lead poisoning, but the disability is not complete because part of the deltoid is innervated by the anterior thoracic nerve, and in lifting the arm, the deltoid is assisted by the coraco- brachial muscle.
Oliver (14), has seen a wide distribution of lead palsy, involving muscles of trunk, back and shoulders, which are painful on pressure. This may come on in acute plumbism, although palsy is typically a feature of the chronic form. Wasting is rapid. If the muscles of
68 INDUSTRIAL POISONS IN THE UNITED STATES
the upper arm are involved, the supinator is also. Palsy of the Duchenne-Erb group of muscles, deltoid, biceps, brachialis anticus and supinator longus, is sometimes seen. The triceps escapes, and although the man cannot bend his arm, he can extend it.
Hall (15), who was in charge of the Mexicans employed in the great lead smelter at Aguascalientes, reported, in 1910, 55 cases of palsy, in only five of which was there a typical wrist drop, and these men were furnace tappers using a long metal rod to coax out the molten slag and matte. ‘Twelve had ankle drop, five paralysis of the deltoid only, three paralysis of the supra- and infraspinati, and 30 the Duchenne-Erb type involving deltoid, biceps, and brachialis anticus.
According to Thomas (16), by 1904 there had been treated in the Johns Hopkins Hospital and neurological dispensary 31 cases of lead palsy, in 26 of which the arms were affected, in four arms and legs, and in one the right leg only, this last being in a painter who had worked all day in a squatting position. The 26 arm eases were divided into 18 with double wrist drop, seven with right wrist only, and one. with left wrist only.
Tanquerel (17) described 112 cases of palsy with varied distribu- tion, the largest number, 97, being in the upper extremities, while the lower extremities were affected in 15 cases. These 97 were divided as follows:
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FIN is Hide 5 bb ah es 4s 55 glee CRORE CRE a Arm, forearm, wrist; fingers... é.iosadanees 4 Forearm: wrist, tingeras [0050.40 4 ek a 14 Wrist, PDGCrS 00605 ink be ahaa eee 26 WEPASE Sie chek & iene +a oo wai os a ee 10 PPO a5 6 os 8 ph RE EN OS ee ee 30
The intercostal muscles were involved in two cases; the dorsal, pectoral and sterno-cleido-mastoid, in one; the abdominal, in five; sixteen had aphonia and 15 stammering; six had disturbance of sight and hearing. Among the 112 cases of motor paralysis there were only five with anesthesia. There were eight with arthralgia.
Legge, reviewing the cases of lead poisoning, notified in Great. Britain during five years, 1904 to 1909, found that the palsies had the following distribution: both forearms, 496; right forearm, 101; left forearm, 36; fingers, 36; arms and legs, 74; legs only, 28; others, deltoid, muscles of speech, locomotor ataxia, general paraly- sis, 10. Chyzer (18), in his remarkable investigation of family lead poisoning in Hungarian villages where pottery making is a house industry, discovered no less than 996 cases. Of these, 114 had marked palsy, 89 of them radial palsy, first of the right
INDUSTRIAL POISONS IN THE UNITED STATES 69
hand, then the left, and sometimes involving the supinators. Eight had ulnar palsy, claw hand. After the palsy of the hands had lasted some time there was in 30 per cent of the cases a gradual involvement of the upper arm. Palsy of the lower extremities was seen only one-tenth as often as hand palsy. It affected mostly the muscles innervated by the peroneal nerve, only once the tibial. He also saw facial palsy. Later, in a personal communication to Teleky (5), Chyzer stated that among 120 cases df palsy there were 14 of the lower extremities, in nine men, four children and one woman. The work of the potter includes turning the wheel by foot pressure. In Chyzer’s cases there is a strikingly large proportion of palsy of the deltoid, and of the muscles innervated by the ulnar, and of the muscles of the legs,—a true palsy, not Remak’s transient weakness. In 1910 I came upon 22 cases of palsy among white lead workers, only five of whom had palsy of the wrists alone, 13 had both wrists and ankles affected, and four had loss of power in the legs alone. These men were unskilled laborers, making coarse movements, lift- ing heavy pots, shoveling, trucking, and dumping. In this con- nection I might mention the statement made to me by an observant superintendent of a white and red lead works, who was trying to convince me that in lead poisoning the lead passes through the skin. He said, “I have noticed that men who work in the lead with their hands get wrist drop, the men who carry loads on their shoulders get palsy of the shoulders, and the truckers who pass to and fro over the dusty floor barefoot or with worn out shoes get ankle drop.” A good illustration of Edinger’s theory as to the localization of lead. palsy was related to me by Dr. A. J. Boucek, of Pittsburgh. _ A man had been employed for ten years filling wooden kegs with _ white lead paint and had never shown any symptom of lead poison- - ing. Then the company he worked for began to use small iron pails instead of kegs. The man had always held the barrel-shaped kegs easily, with his hands placed flat against the sides just below the bulge, but the iron pails had smoothly slanting sides and he could 1 only hold them by crooking the ends of his fingers over the project- _ ing bottom edge. He found the work far more tiring than his old _ work had been, and after a few weeks he came to Dr. Boucek with a double wrist drop that lasted several months. Typical lead palsy of the lower extremities, or “foot drop,” _ affects the long and short peroneal muscles and the common exten- sors of the toes, but the tibialis anticus, which also is innervated _by the peroneal, usually escapes. The foot hangs, cannot be ex- tended, and abduction and adduction are weakened. ‘The plantar flexors, supplied by the anterior tibial nerve, escape. On the other hand, Escherich and Variot (see Edinger (6)) have found in the lead palsies of children an involvement of the tibialis anticus greater
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than that of the peronei. Chyzer found the peroneal muscles involved in thirteen cases, the anterior tibial in only one, and this seems to be the most common form, but the picture is not as characteristic as in palsy of the upper extremities. W. and E. Weber (19) have shown that the extensor muscles of the leg are much larger in men than all the other muscles of the lower extremity put together, and that among the flexors, the adductors and abductors, the tibialis anticus is the most, powerful.
In cases of leg palsy, Remak distinguishes between a weakness of the legs with heightened patellar reflexes which he considers purely functional, often following colic, and a true degenerative lead palsy with normal reflexes.
Oliver calls attention to cases of chronic plumbism which simu- late vascular syphilis with one-sided lesions, palsy of one hand, of one foot, of the external ocular muscles on one side or a limited loss of muscular power, and slight weakness in one limb. Such a result may follow a plumbic endarteritis of the minute vessels of the brain tollowed by degenerative changes of a very restricted extent.
Aside from these localized, usually symmetrical, palsies accom- panied by atrophy but not by severe neuritic pains, a great variety of paralyses have been described in the course of lead poisoning by experienced observers. Dejerine-Klumpke described in 1882 multiple neuritis of plumbic origin. Oliver has seen a widely dis- seminated polyneuritis with severe pain and rapid atrophy, tremors of the muscles, and palsy of the muscles of speech and of swallow- ing. Putnam (20), Bechtold (21), and Oppenheim (22), all re port cases of palsy resembling spastic spinal palsy, with lead in the urine. Kichhorst (23), of Zurich, described a case of spastic paralysis in a painter with undoubted plumbism (line, stippled red cells, lead in urine and feces, colic, palsy), and referred to some earlier cases reported by Frerichs, Bechtold, Escherich, and Weber; but the number of such cases is small. Kichhorst also quotes a case of Philipson’s, of rapid ascending palsy, generalized and fatal. <A similar case, also fatal in a sanitary ware enameler who scattered dry lead enamel over heated ware, was reported to me in 1910 by Dr. Stybr of Pittsburgh (see page 15).
Dejerine-Klumpke says that lead paralysis may simulate Duchenne’s subacute spinal paralysis, that is, a febrile form of gen- eral palsy. According to Gowers, lead poisoning may cause a pro- gressive muscular atrophy similar in localization and features to the usual form, but distinguished from it by the fact that it is not progressive when the exciting cause has ceased to act. Comment- ing on this statement, Collier (24) says that he himself has never seen nor was he able to find in the numerous records of the Na- tional Hospital for the Insane in London, any cases in which un-
INDUSTRIAL POISONS IN THE UNITED STATES 71
doubted lead poisoning was followed by typical progressive muscular atrophy.
According to Oppenheim the typical toxic palsies are those of lead, arsenic, aleohol, and diphtheria. If the effect of lead and alcohol are combined there may be a very rapidly developing palsy, and this, even if alcohol is used in moderation. In such eases we are likely to find other nerves affected besides the arms. He saw a case of painful polyneuritis of legs and arms, apparently typical aleoholic neuritis, but when it cleared up there was left behind an extensor palsy of the hands.
Tanquerel said that palsy usually occurs only after the patient has worked a long time in lead and has suffered repeatedly from colic. He studied 112 cases of palsy, in 63 of which there was a history of colic, and in all but three of these the colic preceded the palsy. In 39 there was no colic. The length of exposure to lead in these cases was as follows: less than a month, six; a month to a year, 16; over one and under five years, 28; six to twelve years, 24; twelve to twenty years, 20; over twenty years, eight. The precursors of palsy are a feeling of heaviness in the limbs, cold and stiffness, espe- cially in the morning, passing off when the man warms to his work. Then he notices that fatigue comes on easily, prematurely; his fingers are numb and powerless, his legs bend under the weight of his body, and pains in the joints may precede the palsy. In eight of Tanquerel’s cases palsy followed an acute encephalopathy. Re- lapses without further exposure to lead are noted by Tanquerel, and he says that Marechal has observed many recurrences of lead palsy years after the patient had withdrawn from lead work. (See page 53.)
Lead palsy tends to improvement or even to complete recovery. Every physician with a large practice in a lead center has seen work- men who give a history of wrist or ankle drop which has cleared up, leaving no trace. Teleky has seen lead palsy disappear completely in eight to ten days. If long continued, however, and accompanied with decided atrophy, such a paralysis may be permanent and in that ease contractures will appear from the action of the opposing muscles.
The proportion of cases of palsy among the total number of eases of plumbisth is difficult to ascertain because official lists of “cases” such as we find usually published, may include every case of plumbism seen, regardless of the fact that the same case may have been seen at the last monthly medical inspection, or they may include each new attack or relapse as a new case. Tanquerel says that he saw 2171 cases of lead poisoning, but if the individual ease histories are counted, the number falls to 1493. Of these, 112 had motor palsy, which would be 7.5 per cent. Teleky, as physician attached to the sickness insurance bureau of Vienna,
72 INDUSTRIAL POISONS IN THE UNITED STATES
saw 1336 cases between 1905 and 1909, 40 of whom had palsy. He says, however, that if he had counted each time he saw a case of palsy he would have had 65, or if he only called each relapse a new ease the number would be 53. His percentages, therefore, would be 2.99 or 3.97 or 4.87, according to the method of reporting adopted. He believes it accurate to count each new attack a new case and therefore chooses 3.97 per cent as his figure. The British rate, which is excessively high, must be explained on the ground of the long duration of palsy, which brings it about that the same patient is seen and notified again and again. Between 1900 and 1909 inclusive there were 6762 cases of plumbism notified in Great Britain and palsy was present in 21.1 per cent of the men and 15.3 of the women. The larger proportion of cases among men is shown also in Prendergast’s (25) statistics gathered in the pottery region, based on 640 cases. Fifty-seven per cent of the men and 30 per cent of the women had palsy.
BIBLIOGRAPHY
(1) Cuarcot. Quoted by Westphal, Ztschr. f. klin. Med., 1896, 17, 1317. (2) Desertne-Kitumpke. Des polynévrites en général et des paralysies et atrophies saturnines en particuliér, Paris, 1889, 295. (3) Gowers. Quoted by Collier (24). (4) Remax. “Neuritis und polyneuritis,’ Nothnagel’s Spez. Path. u. Ther., part 3, Wien., 1899, p. 278. (5) Tretexy, L. “Zur Kasuistik der Bleilahmung,” Deutsch. Ztschrift. f. Nervenh., 1909, 37, 234. (6) Epincer, L. Der Anteil der Funktion an der Entstehung von Nerven- krankheiten, Bergmann, Wiesbaden, 1908. (7) Mogsius. Quoted by Bernhardt (10). (8) Virrorpt. “Zur Frage vom Wesen der Bleilihmung,” Arch. f. Psy- chiat., 1887, 18, 48. (9) Metiton, R. “Relation of Fatigue to Paralysis in Plumbism,” Arch. f. Int. Med., 1913, 398. (10) Bernuarpt, M. “Zur Path. der Bleilihmung,” Berl. klin. Wehnschr., 1900, 26, 37. (11) LivuienFieLp. Quoted by Edinger (6). (12) Manouvrter. “Intoxication par absorption cutanée,” These de Paris, 1873, No. 471. (18) Lappé. “Laihmung der Schulter,” Wiener med. Presse, 1902, 1288, 43
(14) Ottver, T. Allbutt and Rolleston’s System of Medicine, 1909, 2, part 1, 988
(15) Haut. Texas State J. M., 1914, 10, 308.
(16) Tuomas, H. M. “A Case of Generalized Neuritis from Lead,” Johns Hopkins Hosp. Bull., 1904, 15, 66 and 209.
(17) Tanqueret, L. Lead Diseases, a treatise from the French of L. Tanquerel des Planches, trans. by Samuel L. Dana, Lowell, 1850.
(18) Cuyzrer, A. Les intoxications par le plomb se presentant dans la ceramique en Hongrie. Schmidl, Budapest, 1908.
(19) Weper, W. and E. Quoted by Eichhorst (23).
(20) Putnam, J.J. J. Nerv. and Ment. Dis., 1883, 10, 446.
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(21) Becutotp. “Ueber einem Fall von spastischer Spinalparalyse nach eine Bleivergiftung,” Miinchen med. Wchnschr., 1904, 16, 48.
(22) OprenHemM, H. “Allg. u. Spez. iiber die toxischen Erkrankungen des Nervensystems,” Berl. klin. Wehnschr., 1891, 28, 1157.
(23) Eicunorst, H. “Bleivergiftung und Riickenmarkskrankheiten,” . Med. Klin., 1913, 9, 201.
(24) Cottier, J. The Oxford Medicine, New York and London, Vol. 6, 1921, 333.
(25) Prenperaast, W. D. Brit. M. J., 1910, 1, 1164.
CHAPTER 6 LEAD ENCEPHALOPATHY
TANQUEREL pres PLancuus (1), first in 1836 gave the name of encephalopathia saturnina to all forms of cerebral involvement in lead poisoning, but retained Griselle’s classification of three forms— delirious, comatose, and convulsive—to which he added a fourth, the commonest type of all, namely, a combination of these three. Tanquerel says that the most characteristic feature of cerebral plumbism is the great variety of its manifestations. “L’encephalo- pathie est une névrose de lencéphale, 4 physionomie si mobile que du matin au soir, du jour au lendemain, les.symptomes que décéle son existence changent complétement d’aspect ou de forme.” It is, however, the least common variety of lead poisoning, and among Tanquerel’s 1217 cases of industrial plumbism only 72 had cerebral involvement. The warning symptoms are usually severe headache, dizziness, sleeplessness, bad dreams, hallucinations, or disturbances of vision. The delirious form is characterized by confusion, inco- herence, sensory hallucinations, slight tremors, chiefly of arms and face, difficulty in walking, embarrassment of speech and often amaurosis. ‘The comatose form occurs suddenly, often in the midst of apparently good health. There are several forms of the con- vulsive, partial preservation of consciousness being a distinctive feature of lead epilepsy.
In 1880, some fifty years after Tanquerel, Westphal (2), pub- lished a study of lead ertcephalopathy which is still authoritative. He adds to the varieties described by Tanquerel an apoplectic form but he says that even with this the field is not covered; for into the picture of saturnine encephalopathy come features of