INTERNATIONAL LABOUR OFFICE Studies and Reports Serie* 2C^"/ /, _. GENEVA C Vi February 1921. -Oí-, Cancer of the Bladder Among Workers in Aniline Factories. SUMMARY. Introduction — Frequency — Aetiology — Technical Survey— Pathogeny— Pathological Anatomy — Symptoms — Diagnosis — Prognosis — Treatment — Prophylaxis — Legislation—Conclusions —Bibliography. INTRODUCTION. The problem of tumours among certain classes of workers is undoubtedly one of the most interesting questions of labour pathology. It had long been known that tumours existed among chimney-sweeps, petrol refiners, workers handling tar, paraffin pitch, and many other occupations. Some years ago attention was also drawn to the frequency of tumours among the miners of Schneeberg, who were exposed to inhalation of dust containing cobalt and arsenic. I t was in 1895 that Rehn reported to the Surgical Congress 3 cases of tumour of the bladder which the medical officers of an aniline factory at Frankfort-on-Main had sent to him for surgical treatment. In a short time observations of a similar character multiplied. The tumours, however, were of different natures, due to different products. I t was impossible as yet to determine exactly the industrial origin of the tumours, but the Directors of the factories, disturbed by the frequency and the gravity of the tumours noted, placed at the disposal of the experts and technicians all the material necessary for studying the problem and discovering prophylactic measures. The Serological Section of the Höchste Farbwerke took up the question, but the experimental researches carried on for two years did not yield appreciable results. The first cases of tumour were reported among the workers engaged ILO =sry ji llllilllllllllllll 3ITG-I. Il Ir III III ]  ^ i ' ht! r»À — 2 — in the preparation of fuchsine and aniline. Efforts were made to secure the completest possible protection in this branch, but the danger was not eliminated. The Surgical Congress of 1904 again dealt with the question of tumours of the bladder due to industrial causes and instructed Rehn to collect material relating to cancer of the bladder among the workers in aniline factories. The enquiry was carried on in 18 factories, but the cases observed only concerned 7 factories. The study of the question, the work of documentation, and the treatment in hospital of the patients, were entrusted to the Samaritenhaus of Heidelberg; but the results were not very encouraging. The reports published, however, had indicated that other products were capable of engendering tumours of the bladder, and that among those benzidine and naphthylamine occupied the most prominent place. The cases observed were all in the zone of Frankfort, and the question was raised whether the phenomenon might not admit of a different explanation. In 1912, however, Leuenberger published a very interesting study dealing with 18 cases observed among the workers at Basle handling aniline dyes. From that moment the existence of a very close connection between the manipulation of aromatic bases (1) and tumours of the bladder among workers was proved. The question was again brought before the Congress of Factory Physicians of the chemical industry (6th May 1920), which appointed a Commission for the study of the question. The Commission comprises the representatives of the Commission of the Association of the Chemical Industry, of the medical practitioners of Frankfort engaged in the study of cancer, of the Government, the Province, the manufacturers, and the workers. The Secretary, Dr. Curschmann, in a recent pamphlet, has published a questionnaire to be answered, for the purpose of arriving at the most exact statistics possible. He points out that the total number of cases of tumours of the bladder since 1913 cannot be more than 28. Considering the gravity of the question, especially in the case of malignant tumours, and considering the fact that the industry of aromatic bases has undergone a very considerable development in recent years in countries not perhaps (1) Organic chemistry is the chemistry of carbon compounds, which are commonly classified in two groups — compounds of the aliphatic series, or derivatives of methane, and compounds of the aromatic series, which have received that name because many of them possess an agreeable smell. These are also called benzene compounds, because they are derived from a hydrocarbon C6 H„ known as benzene. Benzene and its homologues, toluene (C6 H 3 (CHj)) and xylene (C6 Hj (CH3) s ), form the starting point of a great number of compounds. Among the characteristics of the aromatic compounds may be mentioned the fact that they easüy react in combination with azotic acid, in forming nitrate derivatives, and with concentrated sulphuric acid in producing sulphonic acids. .— 3 — sufficiently informed in regard to the ill effects of these products, a clear presentation of the problem is desirable, especially in view of the fact that the specific action of aminocompounds (1) is only explicable after a long period of contact. Frequency. A certain number of authors do not admit any direct connection between poisoning by aniline and its derivatives and tumours of the bladder. Grandhomme has repeatedly insisted on the fact that no case was noted from 1883 up to 1896 among 493 workers exposed to aniline poisoning, and that during the same period not a single case was reported among the workers (4,000), at Offenbach or Fechenheim. He concluded that aniline may irritate the mucous membrane of the bladder and produce troubles in passing water, pains, etc., but that it has no connection with the production of tumours. The observations of LeicMenstem and Schwerin have completely disproved the conclusion of Grandhomme, and the analysis of published works is very conclusive on this subject : 1895. 1898. 1898. 1900. 1904. 1904. Behn. Three cases, two of fibrop apillo ma and one of sarcoma, among workers in contact with fuchsine and aniline. Bachfeld (of Offenbach) reports 63 cases of poisoning by aniline, toluidine or nitro-benzene, among which 16 exhibited troubles in passing water (strangury). . LeicMenstem : 1 case of sarcoma due to naphthylamine and one case (not clearly characterised from the histological point of view) due to toluidine. Wendel gives the histological examination of the cases of Eehn and Leichtenstern and reports 3 cases of cancer, of which 2 are due to aniline and one to naphthylamine. Rehn repofts on 20 cases submitted to him for surgical treatment; 8 are cases of carcinoma; 5 of papilloma and 7 without particulars. Posner studies one case of cancer due to naphthol (or naphthylamine). (1) By reducing the nitrate derivatives of benzene and its homologues, we obtain the corresponding amines of the aromatic series. Thes form rather feeble bases. They are distinguished as p r i m a r a ^ S tertiary, etc. The chemical properties of the amines ôUffj^^prfSÎaeraDry'yJ^ from those of the amides, which may be considered as interrfeiiate products ^ in the transformation of nitriles into acids. The c a r b / ^ ^ group may *7 undergo changes when substitutions by other elemenj^pr groups are __ introduced : thus derivatives of fatty acids are obtained i y modDEcation of .. ' the carboxyl. I ' "*• i , . fì ^ , V _ 1904. 1904. 1905. 1905. 1906. 1907. 1909. 1909. 1911. 1912. 1913. 1919. 1920. 4 — Strauss. Publishes one case of cancer due to toluidine and benzidine. Bardenlieure. Two cases, one of cancer and one of papilloma. Rehn. One case of cancer of the bladder, ureter and kidney, due to aniline. Schedler. Two cases due to aniline, one of malignant polypus and one of sarcoma. Report on the enquiry made by Rehn. In 7 factories out of 18 in which the enquiry was held, 38 cases due to aniline and aromatic bases were observed. They were cases of malignant tumours, of which 18 were fatal; operations were performed in 17 cases ; 11 of these were still living, but three had already shown symptoms of relapse. Seyberth reports 5 cases, 3 of papilloma, one of adenocarcinoma and one of cancer due to aniline. From the reports of the Labour Inspectors one case is known of papilloma due to aniline and toluidine. (This case was reported under the year 1910). The same source gives one case due to benzidine, without, however, giving the diagnosis. Cesabianchi publishes one case of adenocarcinoma due to fuchsine, and 2 cases of adenocarcinoma of the gall bladder. Leuenberger studies in his thesis 18 cases, 9 of carcinoma, 4 of papilloma, one of sarcoma, one of Sarcocarcinoma, one of cancer of the bladder and kidney, and 2 not specified. Schwerin, who brings into the discussion the fruits of his 21 years practice as a factory physician, collected for the Conference of Medical Officers of Chemical Factories, 117 cases, which he reduced to 100, as 17 were doubtful. During his long practice he had observed 38 cases of tumour of the bladder' of industrial origin, as against one which had no such origin; but no case of carcinoma. • Nassauer studies in his thesis 32 of the most recent cases of tumours. Curschmann reports on the cases of tumours since 1913, the total of which amounts to 58, of which one is badly described and not counted and 17 have been previously reported. Among the 40 which remain, 11 are not cases of tumours, but only of more or less serious troubles of the bladder, and one is a case of cancer of the kidney. Altogether the cases observed since 1913 are reduced to 28. — 5 — According to Curschmann, the total number of cases of tumour reported from the time of the first cases reported by Eehn is 177. The cases of Fehr are doubtful, and those reported by Israel and Casper in Berlin (Urologische Gesellschaft 1913) require closer study before it is possible to decide whether they have an industrial origin. But it seems to us very difficult to accept Curschmann's conclusion, since it is impossible to obtain precise information on the cases prior to the report of Eehn in 1906, inasmuch as the statistics were based on the figures of the Sickness Insurance Funds, and it might easily have happened that the same cases were counted twice. Thus, of the 38 cases of Eehn, 24 had been previously reported and four are doubtful; so that up to the time of the thesis of Leuenberger the total number of cases would be 41; and as it is impossible to say whether or not the 32 cases of Nassauer include cases previously reported, the total up to 1919 would probably be only 87 ; that is, 41 plus the 18 cases of Leuenberger and the 28 cases of Curschmann. The opinion that these tumours were only found in the district of Frankfort-on-Main has been refuted by Leuenberger, who proved the existence of tumours in the district of Basle, among workers handling aniline dyes (dyers). The diagnosis was verified by autopsy in 47 per cent of the cases reported by Leuenberger. " The examination of the question whether the development of aniline dye factories has been parallel with the occurence of more numerous cases of tumour of the bladder in the whole of the population of Basle City has not produced exact results. It has, however, been possible to prove that the number of deaths due to tumour of the bladder was 0.007 % of the average population of Basle City for the period 1871-1880 and that it rose to 0.02 % during the period 1901-1910. " The comparison of the number of deaths recorded among the workers in aniline dye factories due to tumour of the bladder, with the deaths due to the same disease among the rest of the population of Basle has given the following results :— " According to information supplied by the factories in question, the number of workers employed during the period 1901-1910 in the factories producing aniline dyes and aromatic derivatives in Basle City, was 840. In the same period, according to the Office of Statistics, the whole male population of Basle City amounted approximately to 56,500 workers. From 1901 to 1910 six workers employed in aniline dye factories died in Basle City as a result of tumours of the bladder. During the same period, the physicians recorded 12 fatal cases due to the same affection among the rest of the male population of Basle City. " From these calculations, therefore, it appears that in Basle City during the period 1901-1910, the deaths due to — 6 — tumour of the bladder recorded among the workers in factories producing aniline dves and aromatic substances were 33 times more numerous than the fatal cases recorded for the same number of individuals and for the same disease among the rest of the male population, including old men and children." (Leuenberger). The data of Leuenberger are in fact even more striking, inasmuch as the statistics taken from the Surgical Clinic of Basle give figures proving the gr'eater morbidity of the aniline workers : Period. ¡ ! I ¡ Before the development of the Chemical * Industry After the development of the Chemical Industry • Number Tumours ! A ... I ¡ of of the workers : ° y e r s ! Patients Bladder W o r k e r s ] ! I i I 1861-1870 2600 \ 1871-1880 ¡ 3450 I — i 1881-1890 i 4250 , 1 1891-1900 5500 i 4 /iqm \xyui 1Qin Iyiu 16 9650 10 I Tumours of the bladder among men amounted in the period 1901-1910 in Basle City to 16 out of 570 cases of tumour, thus, 7.8 %. At Vienna, according to Gürtel, out of 16,673 tumours only 66 affected the bladder, or 0.39 %. Other authors give the figure as 0.25 % and 0.76 %. At Frankfort, on the other hand, tumours of the bladder, which appeared in the same percentage among the population generally, amounted to from 25 % to 30 % in a period of 23 years among workers of the class with which we are concerned. I t is certainly not necessary to accept the extreme conclusions of Nassauer, who says that all workers in the factories are exposed to the danger of tumour of the bladder ; it is a proposition which may be true in theory, but which fortunately is not so in practice. But the fact remains, although it only affects a minority even among the workers exposed to contact with aniline and similer substances. A percentage would be difficult to arrive at in default of a census of workers in the past. The percentage would in any case be very remarkable, even if we accept the figure of 177 cases given by Cursclimann, out of an average of 80,000 to 10,0000 workers. A classification of the cases reported by different physicians over the period 1895 to 1920 according to types of tumour, age of patients, and period of contact with the poisonous products, would give the following figures :— „ , m Types of Tumour. i No. of Cases ¡ reported- Papilloma Fibroma ! Carcinoma ¡ Sarcoma i Sarcocarcinoma Cancer of the Bladder, Kidney, etc ! Total j Reported as Benign Tumours ' Reported as Malignant Tumours Total I | . . . -.j 24 4I 4 6I I 51 12 15 27 ! . . . Tumours without specification Grand Total Types of Tumour. ¡ 10 . . . 88 i' Age of Patients. 30-40 41-50: Over 50 Begnign Malignant Xot specified 4 i 3 . 1 Total Grand Total 10 4 11 ii 5 14 23 45 Although a tumour which is due to industrial causes generally appears at a precocious period of life (before 40 years : Chimney-Sweeps, Miners etc.,) it must be admitted that among workers in contact with aniline, tumours appear especially after the age of 40. But it would be well to remember in this connection that in such cases the action of the poison develops very slowly and after a very long period. It is more difficult to reply to the question what is the lapse of time necessary for the appearence of the first symptoms of tumour of the bladder. The data are very different and contradictory. Most important of all, the date of the engagement of the workers is not precisely known, and indications given by the workers themselves have to be accepted. In many cases, especially in the past, the diagnosis was made at a very late stage, as the worker had often had no remarkable symptoms. Thus the following data are given in regard to 52 Cases :— Types of Tumour. First Symptoms of arnong \ v oiKers alter 2-5 6-10 11-15 li 2 •| years years years years ,i 1 Malignant . . . . Mixed Not specified . Totals . . 1 2 1 1 1 5 5 1 3 13 1 .>o Tumour wonting 16-30 Over 30 years years i 5 | 2 1 1 — 17 1 3 23 | 5 In six cases it has been impossible to determine the period of latent duration of the tumour. As regards tumours there is no case which had not at least 10 years' incubation (in one case even 35 years); but on the other hand there are cases which develop very early, especially among those caused by benzidine (less than 3 years : Schwerin, but other physicians say 8 and 12 years.) The period is also very brief in the case of naphthylamine (5 years). 12 years is indicated in the case of rubine and longer in the case of fuchsine and of work in the acid-bottle department. Equally interesting in practice is the question of the diagnosis of tumour of the bladder among workers who have left aniline factories. Although the number of such cases is very limited, observations are nevertheless recorded of tumours among workers who had been sent to other department or other factories because they had exhibited vesical phenomena (cystitis). These workers have in most cases come to the doctor for haematuria from two to eight years afterwards, and some have had to be operated on. In order to secure the most exact information possible in the future, it will be necessary to make use of the following Questionnaire prepared by Cursciimann : — 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. QUESTIONXAIBE : Christian Name and Surname. Date of Birth. Address. Married or unmarried. Cases of Carcinoma in the family. Former illnesses. Alcoholism. Venereal diseases. Previous poisonings. Career (Nature and duration of occupations since entering the Factory). Date of entry into the Factory. Department and period of employment. With what substances has the patient worked ? — 9 — 14. How many workers (that is, individual workers and not the total number of workers at any one time) have been employed in the Department during the last 10 years ? 15. Duration of working day. • 16. Overtime. 17. Examination of Urine, result (Proof of colour). 18. Periodical Medical Examination. 19. Examination of Blood, and with what result. 20. Clinical History : First symptoms. 21. Evolution. 22. Diagnosis. 23. Treatment. 24. Operation ; Operator (Eeferring to any publications of the Surgeon). 25. Seat and macroscopic description of the tumours. 26. Histology of the tumour. 27. Anatomical and Pathological Diagnosis. 28. Metastases. 29. Has the patient been able to resume his occupation ? 30. AThere and with what materials has the patient been subsequently employed Ì 31. Relapse. 32. n a s this Eelapse been the subject of an operation ? 33. Did the Relapse shew any deviations from the original tumour ! 34. Have any Metastases been observed ? 35. Termination. Date Signature. 36. Remarks on the actual state of the disease and on its subsequent evolution. Address .. Aetiology. AVhat are the products capable of engendering the morbid form indicated ? The reply is not so simple as one might think. As far as we know, it might be said that almost all the products listed below, or at least the majority of them, may he the cause of tumour of the bladder. I t must be remembered that the worker is not always exposed to the action of a single poisonous compound, even in a single department of the factory, and that unfortunately the details of the cases published do not furnish us with very precise information on this subject. In effect, the reporters limit themselves to citing the raw material or final product without giving us exact information as to the compounds handled by the worker. — 10 — ' The result is that products well knoAvn to be inoffensive, such as naphthol, have been, reported as causing malignant diseases, whereas the origin should be attributed to intermediate or accessory products. The following is a list Of the products which, either singly or in association with other products, may cause tumour of the bladder, according to the studies of different observers : Mtrobenzene (Reim), nitrotoluene (Behn), aniline (Eehn, Wendel, Schedler. Seyberth), aniline and toluidine (anonymous), aniline and naphthol (Eehn), aniline, benzol and toluol (Lewin), aniline dyes (Bardenheure, Bard, Behn, Seyberth, Leuenberger), fuchsine, rubine (Behn, Cesabianchi), benzidine (Behn, anonymous), toluidine (Behn, Leichtenstern), toluidine and benzidine (Strauss), naphthylamine (Behn, Wendel, Schedler, Leichtenstern), naphthol (Posner), naphthylamine and diphenylamine (Behn), phenylnaphthylamine (Behn), xylidine (Behn), cumidine (Behn). Mtro-dyes, triphenylmethane, diphenylnaphthylmethane, acridine, ozazine and thiobenzil have also been indicated. If the enquiry of Reim limited itself to the indication of fuchsine and naphthylamine only, Wendel in 1900 definitely established that the suspected products, such as aniline, toluidine, naphthylamine, etc., all belong to the aminocompounds, thus excluding the nitro-compounds. Poisoning by the latter must be distinguished from poisoning due to amino-compounds, inasmuch as the nitrocompounds are generally more poisonous in proportion as the number of the nitro groups in the nucleus increases. The researches of Leuenberger among workers handlinganiline dyes (Basle City) do not make it possible to give an exact list of the products capable of provoking tumour. I t seems however that the following may be the probable cause :— Safranine, dianisidine, dehydrothioxüine, Congo red, and benzo-purpurine. Experience proves that there is no immunity, and that predisposition plays a great part. There are many factors favourable to poisoning — lack of cleanliness, mal-nutrition, alcoholism, excesses of every kind, damp weather, excessive perspiration, etc. Workers new to the trade, and consequently working without precautions, with whom large skin surfaces come in contact with the poisonous products, are special hable. On other hand, workers remaining a long time in the workshops are more exposed to the danger of introducing by deglutition the products floating in the air. Although the permeability of the skin by the products in question is remarkable, it is certain that the older workers, who are accustomed to take great care of their skins, show a smaller number of cases of poisoning. — 11 — Technical Survey. Let us examine more closely the nature and characteristics of the products which have been indicated as the most probable causes of the injuries reported. Among the products of the illuminating gas industry, tar is undoubtedly of great importance, and a still greater importance has recently been acquired by its derivatives. By means of distillation, coal forms two great classes of products; light oils and heavy oils. From the light oils proceed the benzols which, treated in columnar apparatus, give the hydrocarbons of the aromatic series (benzene, toluene, xylene, etc.). Each of these bodies represents, in its turn, the starting point of a series of bodies extensively used as raw materials, especially in the dyeing industry. By nitration and reduction of the above-mentionned carbides the amino-derivatives (aniline, toluidine, xylidine) are obtained. Benzene is transformed into nitrobenzene in cast-iron apparatus, by the addition of a mixture of sulphuric acid and nitric acid. The introduction of the same mixture in the corresponding aromatic compounds produces nitrotoluene, nitroxylene, etc. . In order to transform the nitro-compounds into aminoderivatives, the aromatic compound is placed in .contact with the hydrogen obtained by the reaction of a small quantity of chlorhydric acid on iron shavings. The simplest of the aromatic bases, aniline, may be considered as derived either from benzol by substitution of the amino group plus one atom of H (amiùobenzene), or from ammoniac by exchange of one atom of H against the phenyl group Cell-, (phenylamine). Since 1864, aniline (amidobenzene, phenylamine CoHr.AzEb) has been prepared by reduction of nitrobenzene in a columnar apparatus, with cooling, etc., carefully avoiding a too powerful reaction, iron shavings and 5 % chlorhydric acid being present. When the reduction is complete, the aniline is distilled under steam, and the reaction being accomplished, the product is alkalinized by means of lime. Toluidine and xylidine are obtained from nitrotoluene and nitroxylene by an analogous process. Among the homologues of aniline must be mentioned the three toluidines CeH-^CHsXAzX») obtained by reduction of the three nitrotoluenes : monoamines: toluidines (xylidines, nitranilines, benzylamines, etc.) : diamines (phenylendiamine, etc.). Fuchsine was first prepared industrially in 1859. The dyes of the rosaniline series are derived either from triphenylmethane, or from metolyldiphenylmethane. The first are described as "para compounds" and are prepared by — 12 — oxydising a mixture of aniline and paratoluidine, or by heating a mixture of nitrobenzene, aniline and toluidine, with the addition of iron filings and chlorhydric acid. One of the salts of pararosaniline and rosaniline is fuchsine C20H20AZ3CI. Formerly, the poisoning might have been attributed to arsenic, in view of the method of preparation, for a mixture of aniline and toluidine (Rotöl) was heated with an extremely concentrated solution of arsenic acid. It is now prepared by treating the aniline with formalin. Naphthaline CioHs is a carbide discovered in 1820, also obtained from coal tar and separated from the fractions of the latter substance which reach a temperature of 180°200°. The products of substitution of naphthaline may be mono, bi, etc. substituted derivatives. The monosubstituted derivatives always exist in two isomeric forms distinguished by the letters a and ?. The « naphtylamine CioH;(AzH2) is obtained by heating « naphthol with ammoniacal chloride of calcium or by reduction of the « nitronaphthaline. Isomeric ß CIOHTAZII» is produced by heating naphthol ¡i Avith ammonium sulphide in a current of ammoniac, or in presence of ammoniacal chloride of zinc Diphenyl, like benzene, is the fundamental carbide of an important series of derivatives. By reduction of nitrobenzene by means of iron, caustic soda being present, and passing through the .intermediate products, azobenzol, etc., benzidine is obtained. Pathogeny. The channels by which the poisonous products enter the body are the respiratory organs (volatile products, for example aniline), the alimentary canal (solid products, for example, the paranitraniline), and the skin and mucous membrane which are very permeable, even by the non-volatile aminocompounds. It is no doubt a question of small quantities of the poisonous product, which must moreover apply their action during a number of years and thus constitute in the organism a quantity sufficient (accumulation ?) to engender the tumour. The local irritant action of these products is proved by the frequent declarations of the workers, who often complain of pains (strangury), and especially by the presence of ulcers on the gland and prepuce. The alterations observed on the skin (tumours) following on contact with the same products must have a pathogeny analogous to that of the tumours of the bladder, since they must be the consequence of the excretion of the products in question through the skin along with the perspiration {Brat Hirt). I t is not possible at present to give the toxic equivalent of these products. Experience has proved that certain — 13 — products in small doses under certain conditions give rise to very grave lesions; others, even in strong doses, do not produce any lesion. I t has in fact been known for a considerable time that many workers, although exposed to the , action of aniline and other products eliminated through the urinary organs, have not shown any signs of vesical lesions. Other substances must therefore be in question. The toxicity of dyes derived from coal tar is also a very complicated question. It is, in fact, often very difficult to judge of the toxicity of dyes, especially as they are not always pure, while experiments on animals are not decisive and individual reaction is very different. Pending positive results, it is desirable to establish very exact statistics, which, as has been said, presents serious difficulties. " Thus, for example, the hypothesis of Rehn that tumours are more frequent in the preparation of fuchsine and rubine, is not accepted, any more than the hypothesis which indicates aniline as a very frequent cause of tumour of the bladder. . Leuenberger has arrived at the conclusion that the tumours are due more especially to the action of the aromatic aminocompounds with one or more hydroxylated nucleii. I t is therefore the intermediate products of the amino-compounds which must be incriminated. During the passage through the organism the amino-compounds must undergo a hydrolysation, an indispensable condition for rendering the products of excretion favourable to the production of tumours in the urinary system. Ktichenbecher has endeavoured to ascertain whether the suspected products (aniline and its homologues, benzidine and other derivatives of diamidophenol, naphthylamine a and (3) really give rise to hydroxylated aromatic aminocompounds. As the result of these researches Kuchenbecker concluded that aniline and its homologues in free para position give rise to hydroxylated aromatic amino-compounds, which may, however, reach the bladder without dangerous action, owing to their being combined with sulphuric acid. In the case of benzidine and naphthylamine (« and ß), on the other hand, there is no production of hydroxylated aminocompounds. The hypothesis, therefore, that tumours of the bladder are due to these products is only valid in certain cases. It is easy to prove that the products with which we are concerned follow a law in their transformations within the organism. This law holds good for the transformation of nitro- into amino-compounds; but it is not yet proved as regards other products. Although experiments in this matter have given excellent results, the question is still open. A fairly considerable part of these amino-compounds, and even aniline itself, do not undergo oxydation in the organism, and are eliminated without modification either through the urine or — 14 — through the respiratory organs (aniline). For this reason, in cases of poisoning by aniline and nitrobenzene, analogous final products — that is to say, ,? amidophenols — may be distinguished in the urine. Intermediate products are also partially distinguished. The toxic product is in both cases the same — quinonimine. In the case of nitrobenzene, one must also take into account the action of nitrophenol. The intermediate products which may be distinguished in the urine have been studied by KuclcenbecTcer, who has also given a practical procedure for diagnosis (see page 18). If he is confirmed, we shall be able to say : 1. What is the toxic substance. 2. What are the alterations produced in the organism. 3. What are the channels of entry into .the system. Eesearches are still in progress with a view to ascertaining whether, 'besides the hydrolysed products of excretion, the final and intermediate' products of oxidation may also engender tumours. It is certain that this holds good as regards the toxic action, and especially as regards the action exercised on the haemoglobin by the nitro-compounds of the group hydroxylated in the organism before being rendered innocuous by etherification. It follows that the position of the hydroxyl group is very important.in the amino group and in the formation of the bivalent phenols (introduction of the two hydroxylated groups) etc., inasmuch as the possibility of obtaining compounds capable of producing quiñones and quinonimines depends upon such position. What becomes of the aromatic carbides is therefore still a problem full of obscure points. This is the case, for example, with the naphthylamine ß. The researches on this point will be carried as far as possible. Very interesting also are the experiments of Curschmann on phenylendiamine, tohiendiamine and paranitraniline, which produce alterations of the vesical mucous membrane which disappear very quickly, without leaving appreciable traces and without giving rise to tumours. Pathological Anatomy. Only the tumours of the bladder due to aniline, the tumours of the lung among the miners of Schneeberg, and those caused by the X-Kays are properly neoplastic formations. The other industrial lesions observed among chimneysweeps and workers handling tar, paraffin, pitch etc., on the contrary, have no title to the qualification of tumours. They are in fact tegumentary proliferations, which sometimes appear as excrescences in which the cellular- elements never lose their normal morphological character or their normal disposition. — 15 — There are very few autopsies or histological examinations of cases of aniline tumours which are complete and which make it possible to classify the observations collected. The anatomo-pathological or histological diagnosis is sometimes so uncertain that a precise classification of the tumours is impossible. Their classification as malignant and benign is too simple. As has been seen, the malignant are very much more frequent than the benign tumours. Out of 88 cases studied, 28 benign tumours have been distinguished, as against 50 malignant and 10 not specified. The seat of the tumours is very different : on the posterior or anterior segment of the bladder, or in the neck of the bladder, most often on the inferior segment and preferably near the neck, so that the urethra is sometimes obliteratedThe tumour rarely has its seat below the meatus of the ureter. Cases have been reported in which the Avhole of the bladder was occupied by neoplastic masses (Papillomatosis). The papillomata do not sensibly alter the mucous membrane. They are very liable to relapse, do not produce metastases, and are not always fatal so long as they retain their original character. If they extend, they may prevent the emmission of the urine, with all its well-known consequences. In consequence of the fragility of the vessels and the form of their villosities the tumour readily bleeds, whence the serious and dangerous haemorrhages well-known among aniline workers. Carcinoma (or adenocarcinoma) generally takes the form of a flattened mass, infiltrating the walls, extending over a greater or lesser segment of the bladder wall, and affecting also the mucous membrane and muscular tissues. Very often the cancer is superimposed on a microscopic or macroscopic papillomatosis of the vesical mucous membrane, and there has been much discussion for and against the metaplasia of the papilloma into a carcinoma. It is a question, therefore, either of typical epithelial tumours (papillary tumours and adenoma), or of atypical tumours (epithelioma). The papillary form is frequently observed, but it is not always a benign form of local evolution capable of transforming itself into atypical epithelioma. Proofs of metaplasia are rare, but it cannot be excluded, at least in certain cases. There are numerous cases, however, especially since the introduction of the periodical examination of workers (cystoscopy 3 ), of papilloma allowing of early treatment. (1 ) Cystoscopy is the examination by the eye of the interior of the bladder which is not normally visible without the assistance of special instruments. The first attempts of Bozzini in 1805 were carried to completion by Nitze (1875), who invented the cystoscope with interior lighting. A tube carried iuto the bladder through the urethra enables the eye of the physician t o — 16 — The tumours, especially the epithelial tumours, are accompanied at an early stage by cystitis and nephritis, often causing death before the tumour has had time to reach the neighbouring parts and to become general. In these cases, metastases are found, into the lymphatic vessels, and even into the wall of the abdomen. Only one case is known of metastasis to the liver and lungs (examination, however, proved that the vesical mucous membrane was intact). ÎJesabianchi reports also two cases of adenocarcinoma of the gall bladder in two workmen in contact with fuchsine (primary tumours?) I t is certain, therefore, that in the whole of the urinary system the constant action over a number of years of hydroxylated aromatic amino-compounds, exercised on the conjunctive tissue or the epithelium, is capable of exciting proliferation developing as infiltration of the urinary passages by an atypical growth of the epithelium of the mucous membrane, with formation of microscopic and macroscopic papilloma, the development of granulated tumours, true carcinoma, adenocarcinoma, sarcoma, etc. The majority of the tumours have an extraordinary polymorphism, but it may be admitted that all the tumours arise from alterations of pre-cancerous tissue, as is observed in the case of tumours due to X-rays, etc. Other authors consider that the histogenesis is still obscure, and that the relationship admitted in clinical practice (aniline poisoning = inflammation = tumour of the bladder) is not yet established. Practice has proved that tumours often appear several years after the cessation of work. The same fact has been observed in the case of tumours and dermatitis caused by X-rays, and it would appear that in such cases the tumours are formed by a processus of inflammation and chronic dégénérescence in the sub-epithelial conjunctive tissue (Bibbet). Symptoms. There is very little information on this subject, but it may be said that the clinical symptoms are the well recognized symptoms of tumour of the bladder. The cases already known without symptoms necessitate the regular practice of cystoscopy, so as to permit of an early diagnosis, among the workers in the suspected occupations. In all cases of haematuria, it will be absolutely necessary to subject the worker to a very careful interrogation in order receive the luminous rays proceeding from the cavity by means of a system of mirrors, lenses or prisms. The interior of the cavity is lighted by special systems of illumination placed in the tube introduced into the cavity and utilising either an exterior or an artificial (electric) source of light. Although the optical systems of cystoscopes with interior lighting are somewhat different, it may, nevertheless, be said that all the apparatus is based on the same principle. — 17 — to make sure that he has not been in contact in the past with amino-compounds. This is necessitated by the fact that cases of haematuria among workers who had left the factory two or even five years previously have been subjected to a systematic treatment due to an erroneous diagnosis of stone in the bladder, urogenital tuberculosis, etc. If the practitioner carefully interrogates the worker he will easily be able to establish whether he has suffered from haematuria in the past. Generally, the disease shows itself by hcematuria, which comes on suddenly without premonitory symptoms. The haematuria is very capricious and may even appear once only. It is accompanied by other symptoms, varying according to the seat of the tumour in the bladder. Pains are rare, more often the patient consults the practitioner for trouble in passing water : dysuria and stranguria. Formerly patients usually called in the practitioner when the tumour was already in a very advanced stage, and treatment was almost impossible. Before proceeding further, it should be stated that bladder irritation, although it is a characteristic of this form of industrial disease, is not always a premonitory symptom of the tumours. It is prudent and desirable, however, to follow it with attention. Bladder irritation which precedes by a considerable time the more serious alterations due to the action of amino-compounds, may appear, disappear and reappear, and even be cured without leaving noticeable traces. In other cases, the tumour develops without the slightest symptom, and the attention of the relations or comrades of the patient may only be attracted by the anaemia or cachexy accompanying the tumour in an advanced state of development. Cystoscopical examination now enables early diagnosis to be made and treatment given, so that it is almost impossible for serious cases to escape detection. It is only in the case of widely extended tumours or metastases that complications may arise, which characterise the final stage of the disease. Diagnosis. It is absolutely necessary to use all the means at the disposal of practitioners for making early diagnosis, especially in cases where symptoms are absent. It is necessary also to obtain information on the past of the worker in order to trace a haematuria or the slightest symptoms of cystitis. Many extremely slight irritations of the bladder have been discovered by means of cystoscopical examination. In the case of workers AVIIO have ceased to be in contact with aniline for a long time, it is necessary to be prudent before diagnosing vesical calculus, haematuria or urogenital tuberculosis. — 18 — An early diagnosis is facilitated by the periodical examination of the Avorkers (urine, cystoscopy). Cystoscopy should be practised with every worker who shows suspicious symptoms, and even repeated several times a month as long as these symptoms persist. It may be thought that such an examination Avili produce a bad impression on the workers; experience shows that this fear is without foundation, especially as the test is free and not compulsory, although strongly recommended by the industrial physician to workers already informed of the danger which threatens them. The examination of urine will be made on the water last passed in the presence of the doctor, and its object will be the microscopic search for the presence of red globules (terminal haematuria). This is not a specific symptom, but it is certain that red globules appear in the urine at a very early period, even when the tumour is not yet capable of diagnosis by the cystoscope. Schwerin has sought to demonstrate the presence of substances capable of engendering tumours, particularly among workers engaged in handling acid-bottles. The results obtained are truly striking, the more so as the quantity of products introduced into the organism is so small that the urine cannot possibly contain perceptible traces of the products of transformation. Kuchenbecker, following an indirect line, has sought for a substance derived from the amino-aromatic group, the action of which as a colouring agent would make it possible to discover the amino-compound present in the urine. By combining the amino-diazotised compound with a derivative of amino-naphthol-sulphate 2-5-7 (phenylic acid 2-5-7) he has obtained a colour which tints cotton with the shades characteristic of each incriminated substance. According to the intensity of the shades it is possible to judge the greater or lesser quantity of the substances present in the urine. It is necessary in order to avoid mistakes that the phenylic acid 2-5-7 should not contain any non-phenylated acids. Benzoyle acid 2-5-7 may also be used. The following is the method :— 50 cubic cms. of urine is cooled in ice and reduced by means of ehlorhydric acid until it attains a slight congo red reaction. Four drops of concentrated ehlorhydric acid are added and a sufficient quantity of double-normal solution of nitrite (1-10 drops) to show an excess of nitrite by reaction on potassium iodide paper and starch. Diazotization is effected by means of 1 cubic cm. of- soda salt of phenyleacid 2-5-7 at 1 %, 3 cubic cms. of a solution of soda, 1 part to 10, and a sufficient quantity of water to make up 100 parts. A small piece of cotton cloth is introduced into this solution; the whole is boiled; the cloth is allowed to remain ten minutes in the hot liquid, and then washed in cold water. With a normal urine the liquid retains its colour or becomes slightly red. If the urine contains amino-aromatic compounds it — 19 — takes a distinctly pink or even violet colour, which also tints the cotton. By this method the urine of workers dealing with fuchsine, and particulary those preparing benzidine and naphthylamine, has been periodically examined. Substances capable of diazotation have thus been traced in large quantities among workers exposed to the inhalation of dusts. The efficacy of the means of prevention adopted has been confirmed by such examination, for the quantity of products in the urine has diminished and even disappeared. For the purpose of obtaining exact data as to the value of the quantities traced, a solution of naphthionate is used as standard. Urine very rich in substances capable of diazotation gives a colour the intensity of which is comparable to that of a solution of 1:20,000 of naphthionate ; urine with a small quantity, a colour comparable to a solution of 1 : 100,000, and, if it contains only slight traces, to a solution of 1 : 200,000. The reaction of Kuchenbecker is sufficiently perceptible. The examination of the blood, of the respiratory organs, etc., gives no indications of any value for the purposes of diagnosis. Prognosis. Prognosis should be very reserved even for benignant tumours (papilloma), having regard to their liability to relapse even after a few months. Relapses after a long period are even more frequent (six to eleven years after treatment). There are certainly cases of cure, but only after operation. One must also bear in mind the possibility of a metaplasia of papilloma into malignant tumours. It may generally be said that death will supervene in from six months to 1 % years after the first symptoms.. The prognosis is infallible in cases of malignant tumours, for they have all a fatal termination even if operated upon (eleven deaths in sixteen cases). Exceptions are known, but they are very rare. Possibly .early treatment will improve the statistics. Treatment. The success of the treatment is naturally in very close relation to the precocity of the diagnosis. There is legitimate ground for confidence in treatment for malignant tumours, inasmuch as a return to capacity for work and a good state of health is thereby assured, sometimes for a considerable number of years. If the papillomata are not too greatly developed and especially if they are in a favourable position, the preference is now for endovesical treatment by destroying the tumour by electro-coagulation under the direction of the cystoscope. The method is a particularly intense diathermic process obtained by a current of high frequency,which is very useful — 20 — for the complete destruction, not only of the papillomata but also of their basis, such destruction being carried out much better and Avith much more certainty by this means than by cystotomic treatment. The diathermic method produces little or no pain; it can be applied in the consulting room; it does not favour the reproduction of the tumour; it obviates surgical treatment and permits of repetition if necessary. This method is also indicated for stopping the repeated and dangerous haematurias produced by the papillomata, and although counter indicated for the treatment of the malignant forms, it is a good palliative in cases of relapse after surgical treatment. Very recent observations, however, have drawn attention to the necessity for the patient treatedwith the high frequency current not to leave the hospital immediately, as want of attention is often the cause of serious and sometimes fatal haemorrhages. The treatment of malignant cases is the province of the surgeon. In general, the results are not very favourable. 66% of the persons operated upon have died, and many of the survivors have speedily suffered relapses. As a medical treatment in the case of tumours in which direct treatment is impossible , washing of the bladder has been proposed (with solutions of adrenalin, gelatin, antipyrin, or resorcin, 1 to 5%.) The last-named is useful in cases of haematuria. Lately collargol in solution of 20% (6-15 cubic cms. to be injected in the bladder under anaesthaesia) has also been proposed, one hour later washing with oxicyanide of mercury ('/¿-'A-, per 3,000), especially in cases with pains and haematuria. Prophylaxis. I t must be said at once that the precautions taken in the factories producing amino-compounds, after the researches and reports of the obsei'A^ers, have yielded excellent results. t i t r a t i o n and reduction particularly are now carried out exclusivly by mechanical processes in closed and wellA^entilated apparatuses. The transport of the masses is carried out either under compressed air or in a vacuum. The efficacy of these precautions is proAred by the following fact : out of the twenty-eight cases reported since 1913, only one took place in the Höchste Farbwerke. It might have been feared that the development of factories producing aniline dyes, and particularly aromatic bases, would have increased the number of tumours of the bladder. The last word has not been said on this subject, for the long period of incubation necessary before the appearance of the first symptoms of malignant tumours has been indicated. But it is to be hoped that the application of the precautions summarised below will suppress the serious form of industrial disease in question. — 21 — The prophylactic measures are as follows :— Well-ventilated work-rooms with absorption of vitiated air and introduction of fresh and, if necessary, cooled air; rigorous cleanliness of floors and walls; absorption of dust. Well-closed apparatus, including the apparatus for the mechanical transport of materials; local absorption of dusts and vapours. Beduced working hours; adoption of shifts, in view of the fact that a very short stay in the incriminated section is sufficient to produce tumours. Working clothes, always strictly clean, closed at the neck and wrists ; gloves and shoes. Daily bath, careful washing before going to the refectory or leaving the factory. Medical examination of workers, both on engagement, and periodically; selection of healthy workers; periodical instructions by the medical officer and director of the section. The periodical examination will include examination of urine as previously indicated. Compulsory notification of haematuria and tumours of the bladder among workers in factories producing aminocompounds.(') Distribution of milk; prohibition of smoking and consumption of alcoholic liquors; assistance to the worker in procuring nourishing food. Legislation. Eegulation of labour in connection with nitro and aminocompounds only exists in Prussia, in which country regulations were introduced by the circular of the-Ministry of Commerce and Industry of the 21st October, 1911. England has introduced the regulation of the manufacture of explosives based on nitro and amino-compounds (Eegulation 30th December 1908). Conclusions. Although it is not possible at present to formulate definite conclusions, inasmuch as the problem still presents too many lacunae and obscure points, it may, nevertheless, be said that :— (1) There is a close connection between the manipulation of certain amino-compound products and the existence of tumours of the bladder. (1) In a recent report (1921) concerning compulsory notification of industrial diseases, it is proposed to add to the list now in force in different countries tumours of the bladder in workers who have 10 years or more previously left work in the explosive and aniline dye industries. I — 22 — (2) The number of cases of tumour of the bladder proved to have occurred among workers in contact with aminocompounds is certainly small. It must be concluded from this that the individual factor plays a great part in the pathology of the disease, seeing that the patients constitute a small minority. (3) Action of long duration is necessary to produce tumours of the bladder. There is no relation, however, between their occurrence and the duration of employment. (4) It is not possible to determine the substance capable of engendering tumours. At present one can go no further than to incriminate the amino-compounds, and particularly benzidine and /maphthylamine. (5) The same substance may produce either simple cystitis, or benignant or malignant tumours. (ii) Hygienic precautions, strictly applied, will assure at the end of a few years the diminution and even the disappearance of the disease. (7) It is, therefore, absolutely necessary that in factories in which workers are exposed to the dangerous action of aromatic bases, the most rigorous application of hygienic precautions should be required. (8) Meanwhile, it is desirable that the industries concerned should continue to carry on researches with a view to ascertaining the dangerous substance, and that the statistical particulars in every case should be very precise and should follow the proposed questionnaire. BIBLIOGEAPHY. Bachfeld. Yergift. mit Benzolderivaten (Anilismus). — Vierteljahrsh. f. gerichtl. Mediz. 1898. Bardenheure. Verhandl. d. Gesell, f. Chir, 1904. Casper. 2. Congress d. Gesell, f. Urologie Berlin 1909. Ordin. Gener. Versamml. Berliner Urolog. Gesell. 28-1-1913. (,'urschmann. Statist. Erhebungen über Blasentumoren bei Arbeitern in den ehem. Industrie.— Ztbl. f. Gew. Hyg. 1920 iJ". 8-9 =V.2. and Congres Int. Maladies Professionnelles, Bruxelles 1910. Grandhomme. "Fuchsin" in Eulenb. Handwort. d. öff. Gesundheitspfl. Berlin 1882. — Die Fabriken des A. G. Farbwerke A'ormals Meister, Lucius & Brunig in sanit. u. soziale Beziehung 1896. Conferenz d. Fabrikärzte d. ehem. Industrie Leipzig 1913. J. Israel. Ordin. Gen. Versamml. Berliner Urolog. Gesell. 28-1-13. Leichstenstern. Harnblasenentzündungen u. - geschwülste b. Arbeitern in Farbfabriken.— Deut, mediz. Woch. 1898. H.45. — 23 — Leuenberger S. G. Die unter dem Einfluss der syntet. Farbenindustrie beobacht. Geschwülstentwicklung. — Beitr. z. klin. Chir. 1912 S. 208. Leymann. Ueber die Erkrankungenverhältn. in einer Anilinfarbenfabrik. — Vierteljahr, f. gerichtl. Mediz. — Concordia 1910 H. 17. Leivin A. Blasengeschwülste b. Arbeitern in Anilinfabriken.— Z'tsch. f. Urologie 1913 Bd. VII H. 4. Nassauer. Über bösartige Blasengeschwülste b. Arbeitern d. organ. Grossindustrie. Diss. Frankfurt a/M. 1919.— Ztsch. f. angew. Chemie Jhg. 39 (1919) S. 333. Cesabianchi. Contributo alla conoscenza dei tumori di origine professionale. — Bamazzini-Anno V. ìsT. 10-12. Posner. Der Urogenitalkrebs in seiner Bedeutung für das Krebs-problem. — Ztsch. f. Krebsforsch. 1904 Bd. 1. Rehn. Blasengeschwülste bei Fuchsinarbeitern. — Arch. f. klin. Chir. 1895 Bd. 50. — Weitere Erfahrungen über Blasengeschw. bei Farbarbeitern. — Verhandl. d. Deut. Gesell, f. Chir. 1904S. 231. — Harnblasengeschw b..Anilinarbeitern. — f. Chir: 1905 S. 231. — Blasenerkrankungen bei Anilinarbeitern. — f. Chir. 1906 S. 313. Schedler. Zur Kasuistik der Blasentumoren bei Farbarbeitern Diss. Basel 1905. Schiverin. Blasengeschwülste. — Ztbl. f. Gew. Hyg. 1920 S.64. Seyberth. Blasengeschwülste b. Anilinarbeitern. — Munch. med. W. 1907 H. 32. Strauss. Blasengeschwülste b. Anilinarbeitern. — Verhandl. d. Deut. Gesell, f. Chir. 1904 S. 237. Wendel. ' Zu der Lehre von den Blasengeschwülste. Grenzgebiete 1900. G. 15. Zuckerkandl. Blasengeschwülste. — Verhandl. d. Deut. Gesell. für Urologie Berlin 1909. S. 391. PATHOGENY. Adler. Wirkung u. Schicksal des Benzidins im Tierkörper. — Arch. f. exp. Pathol. 1908 Bd. 58 S. 1666. Bachfeld. Gewerbehyg. Erfahrungen über die Giftigkeit der Teerfarben. — Ztbl. f. Gew. Hyg. 1920 H. 7. Engel. Über das Schicksal des Naphtylamines im Organismus des Hundes. — Ztbl. f. Gew. Hyg. 1920 H. 5. Keubner W. Ueber das Wesen der akute Mtrobenzol- u. Anilinvergiftung. — Ztbl. f. Gew. Hyg. 1914 H.12. Kuchenbecker. A. Nachweis aromat. Amidoverbind. im Harn. — Ztbl. f. Gewerbehyg. H. 1.— 1920. — Ueber die Umwandlung aromat. Amidoverbindung im Tierkörper. — Ztbl. f. Gew. Hyg. 1920 H.4. — 24 — Mueller R. Ueber die Einwirkungen des Anilins u. des Dimethylanilins auf das Froschherz. — Ztbl. f. Gew. Hyg. 1916 H. 8. — Ueber die Permeabilität der roten Blutkörperschen f. einige Amino -u. Xitroderivate des Benzols.—Ztbl.f. Gew. Hyg. 1914 H.8. Oppenheimer. Ueber die bei den Arbeitern ehem. Betriebe beobacht. Geschwülste d. Harnapparates u. deren Beziehung z. Geschwülstepathogenese. — Muench. med. Wochen. 1920 H. 1. TREATMENT. Roch A. Behandlung der Blasenpapillons.—Prag. med. Woch. 1913 H.51. Oppenheimer R. Zur Erkennung u. Behandlung der Blasengeschw. der Anilinarbeiter. — Ztbl.f. Gew. Hyg. 1920 S. 105 u. Muench. med. Woch. 1920 H. I. Rubrums H. Die Koagulatlonsbehandl. der Blasengeschw. — Prag. med. Woch. 1913 H.51. Schneider C. Ein Pali v. starker Nachblutung nach Operation eines Blasenpapillons mittels Hochfrequenzströmen. — Ztbl. f. Tirol. 1913 H. 7. Sigurtà G. B. La elettro-coagulazione dei papilloni della vescica. — Soc. Lomb. Scienze mediche e biolog. Milano 1916. — 25 — STUDIES AND REPORTS already Issued Where the English or French text of a Report has not yet been published it will be issued at a later date. Series A. N° 1. T H E AGREEMENT BETWEEN THE SPANISH WORKERS' ORGANI- SATIONS, issued on September 25th 1920. French and English. " 2. T H E DISPUTE UNION IN THE METAL CONTROL INDUSTRY OF INDUSTRY, issued IN ITALY. TRADE on September 25th 1920. French and English. " 3. ANNUAL MEETING OF THE TRADES UNION CONGRESS 1920, issued on October 4th 1920. French and English. " 4. INTERNATIONAL CONGRESS O F WORKERS IN THE FOOD AND DRINK TRADES, issued on October 11th 1920. French and English. " 5. T H E BRITISH GOVERNMENT AND THE MINERS' FEDERATION OF GREAT BRITAIN. CONFERENCE BETWEEN SIR ROBERT HORNE AND THE MINERS' FEDERATION, issued on October 11th 1920. French and English. " 6. T H E CONGRESS OF THE LABOUR AND SOCIALIST INTERNATIONAL, issued on October 1+th 1920. French and English. " 7. T H E MINERS' INTERNATIONAL CONGRESS, issued on October 19th 1920. French and English. " 8. T H E INTERNATIONAL LABOUR ORGANISATION. A COMPARISON, issued on October 21st 1920. French and English. " 9. T H E INTERNATIONAL CONGRESS OF METAL WORKERS, issued on October 22nd 1920. French and English. " 10. T H E BRITISH GOVERNMENT AND THE MINERS' FEDERATION OF GREAT BRITAIN. CONFERENCE BETWEEN THE GOVERNMENT AND THE TRIPLE INDUSTRIAL ALLIANCE, ÍSSUED ON "11. T H E DISPUTE IN THE METAL INDUSTRY IN ITALY. TRADE UNION October 26th 1920. French and Englisli. CONTROL OF INDUSTRY. (Second part) ber 4th 1920. French and English. " 12. issued on Novem- T H E FOURTH INTERNATIONAL CONGRESS OF BOOKBINDERS, issued on November 26th 1920. French and English. " 13. T H E MINERS' STRIKE IN GREAT BRITAIN, issued on December 21st " 14. T H E X V t h CONGRESS OF T H E GENERAL CONFEDERATION OF LABOUR (CONFEDERATION GÉNÉRALE DU TRAVAIL) held at Orléans 1920. French and English. the 27th September to the 2nd October 1920, issued on December 23rd 1920. French and English. " 15. T H E INTERNATIONAL CONGRESS OF GENERAL FACTORY WORKERS, issued on January 24th 1921. French and English. " 16. TENDENCIES OF EUROPEAN LABOUR LEGISLATION SINCE THE WAR, " 17. T H E GROWTH issued on February 11th 1921. English OF TRADE UNIONISM only. DURING THE TEN YEARS 1910-1919, issued on February 16th 1921. English and French. — 26 — Series B N° 1. COAL PRODUCTION IN THE RUHR DISTRICT. Enquiry by the International Labour Office, end of May 1920, issued on September 1st 1920. French and English. " 2. PAPERS RELATING TO SCHEMES TION FOR THE DISTRIBUTION OF INTERNATIONAL ORGANISAOF RAW MATERIALS AND FOOD " T H E CONDITIONS OF LABOUR AND PRODUCTION IN THE UPPER SILESIAN STUFFS, issued on October 5th. 1920. French and English. 3. COALFIELD, issued on December 10th 1920. French and English. " 4. T H E SOCIALISATION OF COAL MINES IN GERMANY, issued on January " 5. T H E ESSEN 25th 1921. French and English: MEMORANDUM ON THE SOCIALISATION OF THE COAL MINES IN GERMANY (6 Nov. 20), issued on 28th January 1921. French and English. " 6. WORKS COUNCILS IN GERMANY, issued on January 29th 1921, French and English Series C. N° 1. BRITISH LEGISLATION ON UNEMPLOYMENT INSURANCE, issued on October 26th 1920. French and English. " 2. GOVERNMENT ACTION I N DEALING WITH UNEMPLOYMENT IN ITALY, " 3. T H E BULGARIAN issued on October 27th 1920. French and English. LAW ON COMPULSORY LABOUR, issued on No- vember 4th 1920. French and English. " 4. T H E ACTION OF THE SWISS GOVERNMENT IN DEALING WITH UNEMPLOYMENT, issued on November 13th 1920. French and English. 5. L'ORGANISATION DE L'ASSURANCE-CHÔMAGE E T DU PLACEMENT DES TRAVAILLEURS French EN FRANCE, issued on February 21th 1920. only. Series D. N° 1. STAFF REGULATIONS ON THE FRENCH RAILWAYS, issued on Sep- (Denmark and tember 4th 1920. French and English. Series H. N° 1. CONSUMERS' CO-OPERATIVE SOCIETIES IN Sweden), issued on September 8th 1920. " 2. SEVENTH CONGRESS OF THE BELGIAN 1919 French and English. CO-OPERATIVE OFFICE, issued on September 25th. 1920. French and English. Series K. N° 1. F I R S T INTERNATIONAL CONGRESS OF AFFILIATED TO THE INTERNATIONAL LANDWORKERS' UNIONS FEDERATION OF TRADE UNIONS, issued on November, 1920. French and English. " 2. AGRARIAN CONDITIONS IN SPAIN, issued on November 10th 1920. French and English. " 3. SMALL HOLDINGS IN SCOTLAND, issued on November 12th 1920. French and English. " 4. T H E EIGHT-HOUR DAY IN ITALIAN AGRICULTURE, issued on De- cember 10th 1920. French and English. " 5. L A JOURNÉE DE HUIT HEURES DES TRAVAILLEURS AGRICOLES DEVANT LA CHAMBRE FRANÇAISE, issued on February 10th. 1921. French only. i I ERRATUM P a p e . 6 , line 3 1 : for 10,0000, fread< 100,000, ,, 7, second table, third column,*-for .">, read ' J . ,, 9, line 2 : for the total number of irorkers at any one time, read fvil-time irorkers. ., 11, line 41 : for (Y,IL((,HH)(AZ:N:¡), ,, 12, line r>: delete » CSMHS-.A^OI. read CV,H4(('H3)(A!!H¿).