Document EnmZ94ppX0G3O9KYrELxL0pN

THE JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY Your he 19 SEPTEMBER, 1937 Number 7 the problem of possible systemic effects from ............ CERTAIN CHLORINATED HYDROCARBONS* _ Cecil K. Drinker, Madeleine Field Warren and Granville A. ......... . ._ Bennett Department of Physiology, Harvard School of Public Health and Department of Pathology, ' Harvard Medical School, Boston, Mass. ' HE use of chlorinated naphtha rapidly and thoroughly as possible.! Tlenes and compounds of allied pharmacological possibilities is In brief these cases were as follows: Patient 1. Male, age 21. The previous extremely wide, and with the steamdeydical history of this man was in no way growth of the use of electricity is cer significant except for the fact that he had tain to expand much farther. For an attack of jaundice about 6 weeks prior to years it has been known that many of these compounds cause a troublesome acne, and there is a large literature his fatal illness. Late in December, 1936, he became b'.dlv constipated and had much abdominal pain and distention. When ad mitted to the bo'pital he was slightly jaun upon this phase of the subject. Our diced and was evidently very ill. lie was investigations have not been concerned with chloracne but with the possibility of systemic effects fallowing ingestion or inhalation of such products. In the somewhat, anemic and his skin, particularly upon the arms, face, chest and back, showed many pustules. Bediec aftera brief period in the hospital, and at autopsy was found to spring of 1936, the Halowax Corpora tion, a division of the Bakelite Cor poration, called our attention to three fatal cases of jaundice in workmen using chlorinated naphthalenes and chlorinated diphenyl, and requested that the subject be investigated as * Received for publication June 30, 1937. T The Halowax Company makes many products besides chlorinated naphthalenes, and it has come to our knowledge that all of these products are indiscriminately called "halowaxes" by purchasers ar.-t users, and are lumped together as possib.e causers of acne and even ot systemic disease. S-.nce "halowax" is merely a trade designation, care should be taken to describe compounds by their chemical names and thus avoid condemnations which are both troublesome and misleading. 2S3 09003 WATER_PCB-SD0000032472 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY {.Sept. MS? n,l. 19, no, rj EFFECT have a cirrhosis of the liver with acute yel low atrophy superimposed upon it. This man had been exposed to low concentrations of vapors arising from a mixture of tetr& and pentachlornaphthalenes, together with approximately 10 per cent of a refined chlo rinated diphenyl. While both he and others engaged L-. the same work had chloracne, there were no other disturbances of health in fellow workmen, nor was there any pre cipitating cause for the acute yellow atro phy such as treatment with arsphenamine or exposure to dangerous concentrations of carbon tetrachloride. Patient S. This was a young man who died in February, 1936, after an acute illness characterized by jaundice. He had been ' exposed to fumes arising from a mixture of penta and hexachlomaphthalenes. There is no record of chloracne. The patient worked with a large number of other people of whom but one (Patient 3), a close friend, had significant illness. - Patient S. Another young man employed with Patient 2. He became jaundiced in March, 1936, and died after an illness of 2 weeks. A careful autopsy resulted in a diagnosis of acute yellow atrophy of the liver Here again no history could be ob tained as to a precipitating cause, and there was no record of preceding attacks of jaundice. In addition to these three very re cent fatalities, we have learned of four other possible cases; none of them' fatal. All of these have had jaundice and the entire group consists of isolat-ed individuals who have been picked out of large groups having the same exposure. In but one instance, Pa tient i, is there record of antecedent disturbance of health, and the general health of fellow workers has been good. Such cases have not been reported in the medical literature and only occa sionally can one find reference to sys temic effects of any sort. For exam ple, Courtois-SuSt (1934) reports on work done by Touraine and his essociates (1934) who examined 60 workers who had been exposed to trichlor- 1. A mixture of tri naphthalene. Of these 13 were found na phthaletie. to have mild digestive complaints, 2. A mixture of tet anorexia, nausea and vertigo, but ohloniaphthalen Courtois-Suffit remarks finally, "Ab 3. A mixture of pei sorption is certainly possible and we ehiornaphthalen have for proof of it some of the diges In addition, sublimate tive and general complaints which (3) were collected in u have been due to it. But they appear subcutaneously. to be of little consequence considering None of the animals i the mildness of the digestive troubles tin.1 sublimate from !'2- and the absence of respiratory phe after 2 months were quit nomena." ,, - autopsied. The first ib In Touraine's cases the exposure was nials receiving (3' occur: to a trichlornaphthalene, whereas the ' day and the last died ot American cases of acute yellow atrophy Those receiving the subl were exposed to compounds of higher were even more spvr chlorination. Our own experiments Autopsy in these ani indicate that trichlomaphthalenes re striking changes in the quire enormous dosage, far beyond - described, entirely ch: anything encountered in industry, in acute yellow atrophy t order to produce liver damage. Tel- suggestive to cause the : eky (1927) reported a number of cases___ m:. elude that "certain ehh of chloracne in persons exposed to 'thalenes or impurities chlorinated naphthalenes with a chlo- .. them are capable of pre rine content ranging from 14 to 53 per atrophy of the liver in tt cent. He found that the lower the At the beginning ol chlorine content the less the acne.. - Finn and Jarvik (1936 Mittelstadt (1935) examined a number fact that there have be of cases of chloracne due to trichlor- of acute yellow atroph, naphthalene and reported a number of v- in men working with chic vague general complaints but nothinf Y' thalenes but give no de in the nature of serious disease. Bo* FC to them. Th.ese cases ar garding his animal experimentation, the same as those des Lehmann (1919) reported that ani fanning of this paper. mals fed chlorinated naphthalenes re fused to eat after a time and that, whether poisoned by inhalation or bf jpk.i One may summarize literature upon system! these substances as folic feeding, at death show'ed "peculiar* - w. -y,:.; lesions in the liver. Flinn and Jarvis Uj* L With the exceptioi bon of acute yellow atre (1936) gave subcutaneous injections * gT. d Jarvik (1936) there enormous doses of chlorinated napk" pr even suggestions of . thalenes dissolved in paraffin oil rabbits. The compounds used as follows: Pytfi-3 ^Pon human beings. ' 2. There is evidence ( btat the degree of ehior 000K WATER_PCB-SD0000032473 n,l. 19, no. rj EFFECTS OF CHLORINATED HYDROCARBONS 285 1. A mixture of tri and tetrachlor- nificant in relation to the production naphthalene. of acne. In the work of Flinn and 2. A mixture of tetra and penta- Jarvik (1936) the compounds produc chlomaphthalene. ing serious liver injury were the most 3. A mixture of penta and hexa- highly chlorinated of those tested, chlornaphthalene. though the chlorine contents as given In addition, sublimates from (2) and by analysis vary surprisingly little. (3) were collected in oil and injected 3. There are no published figures subcutaneously. . upon the amounts of various chlorin None of the animals receiving (1) or ated naphthalenes in the air which will the sublimate from (2) died, and even produce injury of any sort, and while after 2 months were quite normal when the work of Lehmann (1919) and of autopsied. The first death in the ani Flinn and Jarvik (1936) point to the mals receiving (3) occurred on the 12th liver as a possible site of injury this day and the iast died on the 26th day, indication rests upon such extreme - Those receiving the sublimate from (3) dosage as to fail to apply directly to were even more severely affected. human exposure.-....... ........... " Autopsy in these animals revealed striking changes in the liver, not, as .. . Experimental Work described, entirely characteristic of In appraising the possible toxicity of acute yellow atrophy but sufficiently any substance met in industry it is -(C ri- suggestive to cause the authors to con first necessary to determine the prin clude that "certain chlorinated naph cipal route of absorption. In the case thalenes or impurities contained in of the compounds under consideration them are capable of producing yellow there can be no doubt that inhalation atrophy of the liver in the rabbit." is their chief means of entering the At the beginning of their paper, body. They are used hot in a great Flinn and Jarvik (193G) mention the variety of operations and volatilize in fact that there have been three cases varied degree. They are often applied of acute yellow atrophy-of the liver in solution in such volatile solvents as in men working with chlorinated naph carbon tetrachloride and toluene. The thalenes but give no details in regard amounts reaching the air under such to them... These cases are undoubtedly-- circumstances are hardly detectable. the sameyas those described in the It will however be shown that carbon ^ginning of this paper.......... . : .. tetrachloride adds to the toxicity of .One may summarize the meagre the chlorinated naphthalenes and allied literature upon systemic effects from compounds, and if there is possibility these substances as follows: of inhaling these compounds in other . h W ith the exception of the men parts of the factory then inhalation of tion of acute yellow atrophy by Flinn carbon tetrachloride adds a decided *d Jarvik (1936) there are no reports hazard. Under such circumstances or even suggestions of serious effects solvents such as toluene should be wPn human beings. used. There is evidence (Telekv, 1927) Observation in a number of plants the degree of chlorination is sig causes us to feel that even though 2S6 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY pVp/. m: workmen may be extremely dirty and careless, comparatively little of these waxes Is eaten. They are tenacious substances, insoluble in water, and if they get on the hands they stick there and arc not transferred to the food. Skin absorption is the third possible means of entering the body. It may occur but at best must be slight when compared to the steady inhalation of finely' divided or gaseous material in the air. tion. They thrive upon a diet very similar to man, and in the case of th"se chlorinated compounds it is possible that diet may be very significant. Finally, their normal characteristics have been described so well as to make the detection of abnormalities both easy' and certain. Method of exposure.--The inhatation experiments were carried out in four iaree air-tight wooden boxes, each capable of holding ten rat cage.-, size .Fig. D_Front view and inflow end of two boxes with rat cages in place and doors open. ;__ Inhalation experiments are then the most important sources of information, but to them we have added a certain number cn observations upon ingestion and subcutaneous injection of various compounds. Inhalation Experiments Animals.--"White rats have been employed throughout. They permit the use of a large number of animals in a relatively small inhalation installa- 22" x 22* x 14", in two tiers of five cages each. When the experiment was not in progress the doors were opened wide and the cages kept in place (figure 1). At the center of one end of each box --the inflow end--air was introduced through a pipe 7. inches in diameter (figure 2). Each box was equipped with an individual variable-speed elec tric blower which blew the air through several feet of 7-inch pipe before enter- 19. no. 7j K inc the end of t meter was placed the How of air in c *1 fnuld be adjusted from a calibratio deflector placed at pipe into tire box Ay >i,re a uniform 'tream of air to th At the opposite outHow end --the fcLY was exhausted thr fitted with a dam] a large central exl About 4 inches die 7-Inch pipe into of the substances dueed into the in daily designed p tfi-ure 4), 7f inche diameter of H int hold the heated w were made with a that extended to top of the flask wa this fitted a short lenech. This short ln;o a large rubber tightly into a hole ct pipe on the under sit fiask in turn was pi heater made to co helow the side arm top. Rubber tubin( dde arm with a com voir and a gentle str through the melted motion and assured hto each flask was in ^tttigrade thermom ePt in place and cou .titne above the 7-in ^hich it passed (figu u approximately 30 .Urinated naphtha! WATER_PCB-SD0000032475 rol. 19, nn. rj EFFECTS OF CHLORINATED HYDROCARBONS 2S7 'me: the end of the box. An orifice chlorinated diphenyl were placed in the meter was placed in the pipe line, and bottom of each flask and melted in the the flow of air in euhie feet per minute electric heater. Fresh samples were could be adjusted and read off directly used every other day', hut it was often from a calibration curve. A vane found necessary to add 20 gm. of new deflector placed at the entrance of the material even after one rim since so pipe into the box was adjusted to as much had sublimed. 'Whatever the sure a uniform distribution of the ease, the collected sublimate was ft stream of air to the two tiers of cages. At the opposite mid of the box--the outflow end--the air from each box was exhausted through a 7-inch pipe fitted with a damper and connected to a large central exhaust fan (figure 3). Abou: 4 inches from the entrance of the 7-inch pipe into the box, the fumes, of the substances listed were intro duced into the inflowing air. Spe cially designed pyrex glass flasks (figure 4), 7f inches long and with a diameter of lj inches, were used to hold the heated waxes. These flasks were made with a side arm and tube- that- extended to the bottom. The ' top of the flask was ground, and into this fitted a short tube H inches in length. This short tube was inserted into a large rubber stopper that fitted tightly into a hole cut out of the 7-inch pipe on the under side (figure 2). The flask in turn was placed in an electric heater made to cover it completely-- below the side arm and ground glass Rubber tubing connected the >:'de arm with a compressed air reservir and a gentle stream of air blown through the melted wax kept it in Fig. 2. Electric heater for maintaining chlorinated compounds at a constant tem perature in place at inflow end of box. ^notion and assured uniform heating. always removed from the upper part Into each flask was inserted a long stem of the flask and a clean top used each j-entigrade thermometer which was day. No sample was ever used for . Pt in place and could be read at any more than two runs. btrie above the 7-inch pipe through The flask plus the contents was care *hich it passed (figure 2). fully weighed at the beginning of the Approximately 30 gm. of pulverized run and at the end, and the loss in 'orinated naphthalenes or 20 gm. of weight used to calculate the average 4 4 4;>>> ^ |;:%^-^^.':;'>^^f-' & * '. '" r'\ri ' V'i,;$ *>. (l,V ; il.V.'W f* M^l; r'-'l * 2SS JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [5epi. i$J7 amount in a cubic meter of air per flowmeter readings. The figures ob minute as determined bv a series of tained were not absolute because of slight variations in the air flowing through the boxes and because of deposition of material on the ther mometers and on the inside surface? of the box, but they checked well with direct determinations through air samples. Approximately 1 hour was allowed for the wax in the flasks to melt and come to a constant temperature. At that time the box doors were tightly closed, air bubbled through the flasks, and the blowers turned on. This was the beginning of the exposure period. By means of rheostats on the fans and dampers in the outflow pipes, the Fig. 3. Outflow end of two boxes showing connection? to exhaust system.- - 773 amount of air flowing through the boxes was adjusted and an attempt was made to keep the four boxes as uniform as pos.sible--usually between 165 and 175 c.f.ra. - - In the first group of experiments the following substances were tested: 1. A mixture of triehlornaphtha- lenesplusa trace of tetrachlornapthuiene. Chlorine content 49.9 per cent. 2. A mixture of penta and he.xa- -i re -- . chlornaphthaienes. Chlorine --.... content 62.6 per cent. ---------3. A mixture of 90 per cent penta and hexaehlornaphthalenes plus 10 per cent refined chlorin ... ated diphenyl. Chlorine con ' tent C3.0 per cent. 4. Chlorinated diphenyl. Chlorine content 65.0 per cent. The compounds were selected as rep" resenting a certain range in chlorina tion and also because of their industrial Fig. 4. Pyrex glass flask importance. In each instance SO \ mals were exposed, 10 rats being placed.-; in each cage. They were fed PurmH kA. ID, no. 7] EFI Dog Chow suppler Pic eggs, milk and cod Thus first group . if- begun on July 1, exposure to numt,v. chloraaphthalenes - 16th. The exposur f compounds ceased y lSth, On October ` tive animals were t sure from groups 1, _ killed after 2 mow 15th, in order to see Co.VDITIOS-S MaI.VTAI.VI Trichlomaphthalenea p gee tetrachlornaphthalen r'^v -Penta and hexach] ornaj 10% penta and bexacl tsaea plus 10% chlorina sEife^: . - ^Chlorinated diphenyl... f.-` period would brmg ^the Elected live: b group 3 were simil xpcure on OctoV. ter examination on Y.Toe average leng 5 hours daily for tb morning at al `m+bu?yL2-'JP$*ij*p0tedp,.ma.ntdheberatwtsei ' etc. In oi of exposun on a resnd? r-.-rw : 000 I I WATER_PCB-SD0000032477 JOURNAL OF INDUSTRLAL. wHYvGriFIENNEE AA.NNDU TOXICOLOGY [Sept. 193^7 290 in question is passed over heated plati test. The concentrations employed num in an electrically heated quartz may be regarded as fairly representa tube and the effluent gas scrubbed in tive of industrial experience. Prior to a column of class beads moistened with the initiation of inhalation experi sodium carbonate containing a trace of ments a number of estimates of chlo sodium sulfite. The beads are then rinated hydrocarbons in the air of dif washed down and the chloride deterferent factories were made and the ptT?nenx. in3*de DiAn.. 50L1D CtASJ SAM inn a aM. foJgV. .zcn. K CLASS WOOL not DCAWNTO scale 5501 iz.. escn. s* -- 301.- OlAM ^ees;jTANC PURNACE NioteoMEwiee QUAKtC 7MM IfCSIP? OlAPt. PI PTTTE -T1 IT-lT~ TIP Fia. 5. Dimensioned sketch PLATINUM FOIL RACKING 6" 1-5"X 0.00/* J5.Z.4 x 3.61 X 0.00^54 <=P1.' -------- . of combustion tube and absorption apparatus. concentrations chosen for inhalation mined nephelometrically as silvtf .er; enxaptieornims.enTtshdeepteecnhdneidc oonf tahneasleyseisxaamnid- chTloeribdbee.ns (1937) has recently the apparatus employed were the work scribed a method and apparatus wtucs^pc: of Frederick R. Millhiser and William should be equally satisfactory for F. Hemperly. ; , .. work. In figure 5 we show a dim^^: The method and apparatus used for sioned sketch of the combustion determining concentrations of chlorin- and absorption apparatus as used ated hydrocarbons in air were adapted us in both our laboratory and from well-known procedures. The air problems. The absorption tube GrcSr, col. 19, no. 7] EFFEC somewhat easier to wau Tebbens's but the essei devices are the same. In both cases conven rinated hydrocarbons acid and subsequent sodium carbonate shou In our case concentrat apt to be very low--t less than 1 mgm. per i quently the amount of actually formed In the : so small that it can not either gravimetrically c For this reason we have use the nephelometric p is sensitive to concent as 0.1 mgm. per cu. m. < It is doubtful if the should exceed 1 liter conversion of the chi pound to hydrochloric subsequent absorption s unless the velocity of th low. Another precautv b that the method is : any chlorinated subs: determined. Furtherm distinguish between soli gases but determines the the results must, of cc puted in terms of total At the present time lormation as to the am rioted naphthalenes in ^iSerent plants, and in instances the measuremi jk.^peated several timei amounts have beer those used in our exper be remembered J'The combustion and a '^"suited to field aampli ^nui*on Products, Inc. equipment includes D pump with a carryin 00012 r.fsdrJ WATER PCB-SD0000032478 rol. 19, no. 7] EFFECTS OF CHLORINATED HYDROCARBONS 291 somewhat easier to wash down than is Tebbens's but the essentials of the two devices are the same.* In both cases conversion of the chlo rinated hydrocarbons to hydrochloric acid and subsequent absorption os sodium carbonate should be,complete. In our case concentrations in air are apt to be very low--the objective is less than 1 mgm. per cu. m. Conse quently the amount of silver chloride actually formed in the final reaction is so small that it can not be determined tith;.: gravimetrically or by titration. For this reason we have been forced to use the nephelometric procedure which is sensitive to concentrations as low as 0.1 mgm. per cu. m. of air. It is doubtful if the sampling rate should exceed 1 liter per minute as conversion of the chlorinated com pound to hydrochloric acid and its subsequent absorption are not efficient Unless the velocity of the gas stream is low. Another precaution to be noted is that the method is not selective-- any chlorinated substance will be determined. Furthermore it does not distinguish between solid particles and Sases but determines them all alike and the results must, of course, be com puted in terms of total chlorine. At the present time we possess in formation as to the amounts of chlor*n&ted naphthalenes in the air of 30 ^dferent plants, and in a number of ^stances the measurements have been ^P&ated several times. Frequently ^ amounts have been greater than ^loae used in our experiments, but it be remembered that the rats combustion and absorption appa ll- to field sampling is now made ulson Products, Inc., Reading, Pa. metin'e9mPment includes flowmeter and n pump a carrying case. have been exposed for 16 hours to an atmosphere constantly impregnated with the substance under test, whereas human exposure is usually a variable quantity, intense for a short time and then negligible. It is our opinion at the present time that the concentra tions of chlorinated hydrocarbons used in our experiments would be dangerous for workers in the case of compounds above trichlomaphthalene in chlorina tion. Fortunately it is easy to venti late processes of manufacture* which require these substances and to reduce air con lamination practically to the vanishing point. Such treatment of the problem at once removes both the possibility of systemic poisoning and the annoyances that arise from cases of acne. Results of Inhalation Experiments. 1. Animals exposed to a mixture of trichiornaphthaienes plus small amounts of tetrachlomapthalene. Living animals were apparently en tirely normal. Autopsies performed near the end of exposure seemed to show slight swelling of the liver, and microscopic examination occasionally showed swollen and bvpergranular liver cells. The changes were, however, never more than slight. 2. Animals exposed to a mixture of penta and hexachlornaphthalenes. No abnormalities were observed in the living animals. Rats were killed and aubopsied every 6 weeks. In the first animals sacrificed liver changes were observed. These were swelling of cells, slight granulation and hyalinization. In September and October these conditions were somewhat more ad vanced, and in November the process became stationary. There were highly w-tj ____ a i',3! Si! US!--- m 292 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [Sepi. im granular cells, hyaline inclusions and exposed to these compounds without mitotic figures, but no more than 2 illness of any sort. months previously. 3. Animals exposed to a mixture of The functional appraisal of the liver 90 per cent pent a and hexachlor- damage caused by certain chlorinated naphthalenes plus 10 per cent refined naphthalenes and by chlorinated di chlorinated diphenyl. No abnormali phenyl.--There are no tests of liver ties were seen in the living animals. function useful in such minor degrees After 6 weeks the livers showed of liver damage as were produced in changes similar to those in the animals these experiments. Indeed the ani exposed to penta and bexachlornaph- mals resisted tht injury so perfectly thalcnes. These advanced in grade as to display no abnormalities except during August and September and upon histological examination of the then became stationary. liver. The situation was perhaps 4. Animals exposed to chlorinated similar to that met in industry, where, diphenyl] No abnormalities were seen barring acne, the health of workers in in the living rats. After 6 weeks' ex these compounds has been good with posure there was slight liver damage the exception of the fact that in iso which advanced during the next 2 lated instances jaundice has occurred months. The changes consisted in which upon at least three occasions slight to moderate swelling of the liver has gone on to acute yellow atrophy. ...cellsf_an_. increased granularity and . _ During recent years this disease has "many mitotic figures. Hyalinization been seen following administration of was always present as a result of _ carbon tetrachloride, arsphenamine inhalation of chlorinated diphenyl. and cincophen. In the case of carbon Summary o/ the first inhalation ex tetrachloride it is known that a low- periment.--In these experiments care calcium diet and alcohol favor the pro ful observation of appearance, body duction of liver damage. For the weight, activity, blood, and urine acute yellow atrophy that occasionally showed no abnormalities of any sort. complicates use of the other two drugs _Yet. after 6 weeks' exposure all the no cause can be assigned. One cannot . compounds with chlorination above produce acute yellow atrophy v.J -trichiomaphthalene caused minor de arsphenamine, but somehow or otter grees of liver damage, and no changes this now and then does happen to p*_ whatsoever in other organs. There tients under antisyphilitic treatment. was no acute yellow atrophy, or any It occurred to us that something of thing suggesting it except that a slight the same sort might be involved in this ^ degree of liver damage was always problem. The human cases have been present and was quite clear in the liver scattered and few. They have been sections examined microscopically. isolated instances out of large group* This damage had no detectable effect of healthy employees who have had g|; on the health of the animals. They equal degrees of exposure. It was our held their weight, ate and behaved idea that perhaps many of these peop^ normally, being in every respect similar got liver changes such as existed in o& to the many people who have been rats, changes not recognizable through &*< I *3* ir tot. 19, no. 71 EFF! any means other th; nation. If, upon t such changes, they disturbance, acute c not a very commoi which any of us may this relatively inne over to acute yellow Knowing that oi had liver chances, slight to cause : ecog we decided to test substances known : struction. Carbon alcohol were selecte mation that 1.0 cc. chloride plus 1.0 cc per kilogram would normal white rats, w to 0.75 cc. carbon 0.75 cc. of ethyl ale This mixture was tube to the foiiowi: mals and with the n following tabulation Rais fed 0.75 cc. per . tetrachloride and stomach 1. Trichlornaphthaier chtornaphlhalene. Fed 10, 1936. 10 rata. No 2. Penla arui hczachlc 9:30 a.m.., Nov. 10, 1 3 died Nov. 11th 3Er.'' 1 died N ov. 12th a: 1 died N ov. 12th at 1 died !Nov. 13 th 11:30 a..m. . lESV3*' 1 died N ov. 15th be 14th and 12: 3C SfSiitfe*.; died Nov. 16th not. ist: 36th (stiff ttiJUper cen! ? nd 10 per 10:(X) a.m. l 00017 81.VI'S# WATER_PCB-SD0000032480 oof. 19, no. 7] EFFECTS OF CHLORINATED HYDROCARBON'S 293 any means other than autopsy exami nation. If, upon the substratum of such changes, they got an acute liver disturbance, acute catarrhal jaundice, not a very common disease but one 1 died Nov. 10th between 5:00 and 10:30 p.m. 5 died Nov. 11th between 4:30 and 10:30 p.m. 1 died Nov. 11th between 4:30 p.m. and 9:00 a.m. Nov. 12th. which any of us may experience, would this relatively innocuous disease go over to acute yellow atrophy? Knowing that our inhalation rats had liver changes, but changes too slight to cause recognizable symptoms, 2 died Nov. 12th about 1:00 a.m. 1 died Nov. 13th between 5:00 and 10:00 p.m. 4. Chlorinated diphenyl. Fed at 10:00 a.m., Nov. 10, 1936. 10 rata. 1 killed Nov. 10th at 10:30 p.m. (almost dead). we decided to test their resistance to substances known to cause liver de struction. Carbon tetrachloride and alcohol were selected. Having infor 2 died Nov. 11th between 4:30 and 10:30 p.m. ' 1 died Nov. 12th before 8:30 a.m. (stiff). . 1 died Nov. 13th between 9:30 and 11:00 a.m. mation that 1.0 cc. of carbon tetra 1 died Nov, 16th between 10:15 p.m. chloride plus 1.0 cc. of ethyl alcohol per kilogram would kill 14 per cent of normal white rats, we reduced the dose to 0.75 cc. carbon tetrachloride and Nov. 15th and 9:00 a.m. Nov. 16th (stiff). Controls: Fed at 9:30 a.m., Nov. 12, 1936. 10 rata. 1 killed Nov. 13th for normal liver. 0.75 cc. of ethyl alcohol. This mixture was given by stomach tube to the following groups of ani-" mals'and with the results found in the following tabulation. This tabulation summarizes into the facts that: ' .. 1. No normal rats were killed by carbon tetrachloride and ethyl alcohol. 2. No trichlomaphthalene exposed Rais fed 0.75'cc. per kgm. each of carbon - --- - tetrachloride and ethyl alcohol by - . ' . stomach tube 1 * 3 rats were killed, and this finding agrees with our inability to find lesions of moment in the livers of the animals that inhaled this substance. 1. Trichlomaphthalenc plus trace of tetrd- 3. The penta and hexachlorinated chlomaphlhalene. -Fed at 9:00 a.m., Nov. 10, 1936.1 10 ratan. No deaths. 2. Penta and hexachlornaphlhalenes. Fed at 9:30 a.m.rNov..lO,1936. 10 rata. 3 died Nov. 11th between 4:30 and .......... 10:30 p.m. naphthalene, the mixture of these with 10 per cent chlorinated diphenyl, and finally the latter substance alone seem to have produced conditions lowering the resistance to an agent capable of . 1 died Nov. 12th at 3:20 p.m.' .. 1 died Nov. 12th at 4:30 p.m. 1 died Nov. 13th between 9:30 and _ 11:30 a.m. ' ' . . .1 died Nov. 15th between night o( Nov. 1 " -- 14th and 12:30 p.m. Nov. 15th. 2 producing serious liver disease. . 4. The sole lesion produced by this test of liver function was acute yellow atrophy usually accompanied by jaundice. died Nov. 16th between 10:15 p.m. Nov. 15th and 9:00 a.m. Nov. 16th (stiff). 3. SO per ceni pcnta and hexachlornaph- Z^enes and 10 per cent chlorinated diphenyl. This test of liver function was ac complished with a substance which itself is an organic chloride and curi ously enough it is the only substance 10:00 a.m., Nov. 10, 1936. 10 rata. we were able to find that was effective. 294 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [Sept. 19S7 In animals with the minor degree of liver injury which has been described we were unable to produce acute yellow atrophy or any variety of liver effect with arsphenamine, cincophen, butyl chloride, ethylene chloride and tetrachlorethvlene, but carbon tetrachlorh was uniformly effective in dis closing the existence of liver damage. Recovery from liver damage following removal from exposure.--Animals ex posed to trichlornaphthalenes plus traces of tetrachlornaphthalene being practically normal on removal from exposure need no consideration. In the case of the penta and hexachlor- signs of liver injury will be many months in returning to normal. The effect of high concentrations of trichlornaphthalenes with traces of tetrachlomapkthalene.--The first group of inhalation experiments showed that this material in concentrations averag ing 1.31 mgm. per cu. m. of air was relatively innocuous, judged both by direct observation and by the carbon tetrachloride test. This is an in teresting fact since such compounds cause acne, though less potently than substances of higher chlorination. In order to explore the matter further one of the inhalation boxes was arranged ------- TABLE 2 orConditions Maintained during Inhalation High Concentrations or Trichlornaphthalenes plus Tetrachlornaphthalene WATTRIAL ' " "' temp. A^. CONCJCKTRATJOJf _ or AJR IN BOX TOTAL at. dailt EXPOSURE xxpoacx* . Trichlornaphthalenes plus traces of ---------- - tetrachlornaphthalene . .... c. mg./cu. m. 137-200 10.97 range High 16.49 Low 5.78 k&lirt 1232 16 ^naphthalene, rats after 2 months' re moval from exposure still showed swollen liver cells, increased granu larity, hvalinization and mitotic fig . ures.. The condition was not advanced as compared with rats killed at the time of removal from exposure but on the other hand 2 months were insuffi cient for recovery. ................. ... The same findings were true of the mixture of penta and hexachlorinated naphthalenes and chlorinated diphenyl and for chlorinated diphenyl alone. Apparently the changes induced in the liver cells by these substances are exceedingly persistent and one must expect that an individual showing any so that fumes from four glass contain ers were delivered to the air line instead of one. This resulted in the conditions shown in table 2. The animals sub jected to these conditions showed no clinical effects of any sort. After 1 month the liver cells were slightly swollen and over-gTanular and there were occasional mitotic figures. These changes were similar to the early. effects of more highly chlorinated . compounds, and progressed oalT; slightly during the third and fourth^ months. When rats in this condit10^ were given carbon tetrachloride alcohol, in some instances their livcJ1.r showed massive central necrosis opd-1 rol. 19, rw. 7| EF1 in others this did r rats were used in t! or.e may conclude |: cblornaphthalenes i ife- toxic as tho=e of i they are not entire! & upon the liver if hi/ traiions are inhaled The effects f lug. penta and \cxaa There can be no dot age done the liver bt but in the concent ported no symptom: could be recognise nothing approachii Conditions Mai>XT ain; WArrarxi .11111' Penu an(f hexachlorna- -jjpg- ` atrophy occurred t use of the carbon On December 1, 1 subjected to the marized in table 3 was terminated on J % the animals lost w< and deaths began af sure. Fifty-five ra them heavily jaund for microscopic ex. killed by the carbon and 8 lived throu; ,l*xpoeure. The live ykiBed for examinatic flatty degeneration, J|m*ith necrosis of livei "rUtairnaljj showed pron r: - 0001U m 'm WATER_PCB-SD0000032482 296 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY (5cp(. 19S7 centrations of these compounds such as were employed cause a certain de gree of liver damage even if inhaled for but 8 hours daily. This injury is re.-isted successfully by the rats just as was the 16-hour injury but it is none the less there and destroys the ability of the animal to resist the carbon tetrachloride test. Summary of inhalation experiments. The findings that have been described briefly will be amplified upon the pathological side in a further paper by Dr. G. A. Bennett. What has been given is, however, sufficient to indi men never inhale enough of any of these substances to get acute yellow atrophy. They may, however, acquire a substratum of liver damage upon which acute yellow atrophy may de velop. Experience in a number of plants has shown how easy it is to reduce concentrations of these com pounds practically to the vanishing point, and every effort should be made to attain such conditions. Gross Feeding Experiments The various compounds used were ground as finely as possible and mixed with a standard balanced ration for . TABLE 4 ' Condition's Maintained during Inhalation or Low Concentrations of Three Compounds during 8-Houb Instead or 16-Hour Periods * UATZBIAL TXUT. AT. CQNCXXTBATIOH or axb lx box EXPTOO&TtATLHX AT. DArLT rrroacxB --- Penta and hexachlornaphthalenes.......... c. 149-193 mf./cu, m. 1.44 90% penta and hexachlomaphthalenes plus 10% chlorinated diphenyl............ 150-197 1.66 Chlorinated diphenyl.................................. 153-174 0.93 ran High 2.58 Low 0.42 High 3.30 Low 0.56 High 3.23 Low 0.03 Kourt 920 hour* s 912 8 920 8 cate that compounds more highly chlorinated than trichlomaphthalene are capable of causing liver injury ' when inhaled steadily in quite low concentrations. It is an extraordinary thing that even the most searching examination fails to show injury in any other region. It is not easy to grade the toxicity of the different compounds tested, but the chlorinated diphenyl is certainly capable of doing harm in very' low concentrations and is probably the most dangerous. Industrial experi ence combined with these experiments make it appear probable that work the white rat. The food was placed in a single container, at which the 10 animals in a cage had an equal chance, the amount of the compounds added being reduced as the number of rats lessened during the feeding period. The experiments were designed to pv an idea as to the possible toxicity o! the compounds selected and, if toxicity was observed, some idea as to the sit or sites of damage. _ ' The experiments were successful u> both respects, and indeed one anticipate that future appraisals of the possible toxicity of chlorinated hydro*' rol. IS, no. T] EFFEC feeding and do not rc rate apparatus and th sary for inhalation exj essential reason for tin :n the identity of the 1 by both methods, and different compounds .-com to arrar.no thorns so far as toxicity is c ever way the}' arc ad: Trichlornaphtkaicne LLrachl-orncphthaknc.on May 4, 1936 mi until 'November 2,193( nine 3 gm. of this mix to the food for 10 and this concentration throughout the exper animals were killed < which died on Nov. 2. loss of weight and nc wasting illness of any s death was due to sorc spiratory infection wh. tion to the material in Histological exarni slight changes in the li of great significance. Tetra and ventachW. Feeding began on Jur dosage of 0.5 gm. daily All the animals sickene ^ere either killed or _ 29, 1936. At autopsy both gn 5?cally the liver was ` yr~^Sected. The liver cel hypergranulation, `joos and vacuolatii toere necrotic cells wen ^'*'88 a tremendous accu ~S Henta and hezaekloi Feeding began Ms; 4 being used. E WATER_PCB-SD0000032483 tol. 19, no. 7) EFFECTS OF CHLORINATED HYDROCARBONS 297 carbons may often be made by simple rats had died. The last one was obvi feeding and do not require the elabo ously ill and was killed for autopsy rate apparatus and the expense neces examination. All animals lost weight sary for inhalation experiments. The from the beginning and were ill. At essential reason for this opinion resides autopsy the liver alone was affected, in the identity of the lesions produced the lesions observed being similar to by both methods, and - he fact that the those that have been described for different compounds so far studied tetra and pentachlornaphthalenes but seem to arrange themselves idea r eally worse. so far as toxicity is concerned which 90 per ccnl p-rnta and hciachlor- ever way they are administered. naphthalcnes and 10 per ccnl chlorinated Trichlornapluhalcne plus traces of diphenyl.--Feeding began May 4, tetrachlcrnapkthalene.--Feeding began 1936 on a 3 gm. dosage. On May on May 4, 1936 and continued 16th feeding was stopped but all until November 2,1936. In the begin the animals went on to death, the last ning 3 gm. of this mixture were added eying on June Sth. .An autopsy the to the food for 10 rats each day, liver lesions were extremely severe and . and this concentration was maintained of the usual type. throughout the experiment. .All the On account of the high toxicity of animals were killed except the last the 3 gm. dosage, four rats were given which died on Nov. 2. There was no a 0.5 gm. dose every other day. Feed loss of weight and no appearance of ing began June 24, 1936 and the last wasting illness of any sort. The single animal was killed Sept. 11th. There death was due to some variety of re were no deaths but all the animals lost spiratory infection which had no rela weight. At autopsy the liver as usual' tion to the material inhaled. ' was the single organ affected, the ' Histological examination showed lesions being characteristic and ex slight changes in-the liver but nothing tensive. of great significance. . Chlorinated diphenyl.--Feeding be Tztrg and ventachlornavhlhalenes.-- gan May 4, 1936 on a 3 gm. dosage Feeding began on June 29, 1936. A and was discontinued on May 10th. .dosage of.0,5 gm; daily was employed. Seven of the 10 rats were dead by May All the animals sickened gradually and 12th. The three remaining rats were either killed or died by August gained in weight but w^ere sacrificed 29,1936. for autopsy purposes on July 8th. -A_ t autopsy both grossly and histo-` The liver changes began at once. Really the liver was the single organ ^-"There were no changes in other organs. affected. The liver cells showed swell- A second group of 10 rats was fed a hypergranulation, hyaline inclu- much smaller dose--0.5 gm. every fijons and vacuolation. Here and other day. Feeding began May 20, necrotic cells were found. There 1936. The first rat died on May 29th & tremendous accumulation of fat. - Penta 07Mf hezachlomaphthalenes.-- ^*-ding began May 4, 1936, a 3 gm. dosage being used. By June 6, nine and four more before June- 24th. The remaining were sacrificed. Those rats that died showed losses in weight, while those sacrificed had recovered -S.R 29S JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY {Sept. 1337 rot. 18, no. effec their initial loss in weight and were gaining, The liver lesions were similar to those found in rats fed penta and hexachlornaphthalenes plus 10 per cent chlorinated diphenyl but not so marked. Summary of gross feeding experi ments.--Of the various materials fed rats in large doses trichlornaphchalene plus traces of tctrachlornaphthalene was quite innocuous. Tetra and pcntachlornaphthalene showed definite liver damage. Penta and hexachlor naphthalenes caused a similar grade of injury. The addition of chlorinated diphenyl to penta and hexachlomaphthalenes increased the toxicity. Chlo rinated diphenyl alone produced liver lesions but in the dosage used was. less effective than when mixed with highly chlorinated naphthalenes. In no case jiid the compounds used produce acute yellow atrophy but the lesions ob served indicate this might be possible if one found a dosage which could act for the'proper period of time. .. Feeding Precise Doses by Stomach Tube The compounds employed were sus . pended in gum acacia. In figuring the -dosage_.tke total amount a man of 50 kgd_would inhale in an S-hour day assuming an air concentration of 20 men. per cu. m. was first calculated and reduced to milligrams per kilo gram. The rats and rabbits received this dose each day. The compounds used were those employed in the gross feeding experiments and the results were essentially similar though the lesions were less severe. Subcutaneous Injections The same gum acacia suspensions were injected subcutaneously into rats and rabbits, the dosage being calcu lated on the basis of 4 mgm. per cu. m. of air. Again similar results were obtained. In all such experiments there must of necessity be different s in the degree of effect but invariably the liver was the sole organ affected and the lesions were those already described many times. Drscrssio.v These experiments leave no doubt as to the possibility of systemic effects from the chlorinated naphthalenes and chlorinated diphenyl. As in the cm-e of the effects upon the skin, the degree of chlorination seems to determine the systemic toxicity, and it is a striking thing that when trichlomaphthaiene is reached systemic effects are never marked and are produced with the greatest difficulty. It is most remark able, too, that all the compounds . tested attack the liver and the liver alone. During the past few months _ we have determined the organically ;; combined chloride b the livers of ani- _ mals very severely poisoned by penta y.and hexachlornaphthalenes but have j; found no increase over normal figures, .y though the livers, as determined histo- -f logically, were very severely affected, m At the present time we are conducting - inhalation experiments on a chloric- ated diphenyl containbg 55 per cea of chlorine instead of 64 per cent in the case of the experiments reported ..yg:;--., in this paper and on a compound a chlorine content between tri tctrachlornaphthalene. We are determining the degree to which diet may increase or decrease toxici^nr this being suggested by similar v upon carbon tetrachloride. ... In the basis of these experimfDt*j% and on many field de different compounds in rooms, it appears .-ah ^tainly easily attained, ftg jr^t ^that the air breathed c ^ more than 0.5 mgm. p< ? /`"of these compounds ^naphthalene. In the c icompound concentrat'd: are permissible. We many examinations in plants that such ccno been greatly exceeded 20 years, and we are c fact that our rat e been inexorably con human exposure is ne' Time and careful ob gk change these opinions but today we are com _ safe. Impregnating t r arrangements utilizing hydrocarbons are easy _ safeguard. Compared lead tetraethyl and m: CovKTOis-Scrrir: Etude - professionnelle par ! taleue. Ana. de m4d (1934). Abstr. of pap A., AND MtNETREL, prefesaiotmelles par 1 tea derives. Prat, n 335 (1934). ir Pnnrx, F. B., and Jajrvie. eertain chlorinated nap liver. Proc. Soc. Exp( U8 (1938). K. B.: Kurie: Albeits- und Gewerbe't id, Leipiig, 1919 (p. 2,' uluy- WATER_PCB-SD0000032485 fol. 19, no. 7] EFFECTS OF CHLORINATED HYDROCARBONS 299 and on many field determinations of pounds, these substances are very different compounds in the air of work little toxic and operations employing rooms, it appears safe and it is cer- them can easily be safeguarded. It plainly easily attained, to ventilate so^may be argued that where possible -tAh1 atA Ath1 e a!ir_ breathed does nnrotft cnortnnttmainn ' ftrMicnhVil1ortr*n-nanpnhVtihtkanllennneft sflhinoiuiUld be used,V\ ft n.-rt/-l ^more than 0.5 mgm. per cu. m. of any^ but this compound will cause acne and ^of these compounds abovg trichlor- if employed very carelessly might do >^haphthalene. In the case "f the latter more. Furthermore, higher chlorina compound concentrations of 10.0 mgm. tion is often essential for highly prac are permissible. We know from tical reasons. The solution consists ir. many examinations in many different thoroughly adequate ventilation plus plants that such concentrations have been greatly exceeded during the past 20 years, and we arc conscious of the fact that our rat exposures have been inexorably constant" whereas human exposure is never so ordered. Time and careful observation may change these opinions as to standards, but today we are convinced they are safe. Impregnating tanks and other arrangements utilizing the chlorinated hydrocarbons are easy to hood and to V, safeguard. Compared with benzene, lead tetraethvl and manv other com- good housekeeping around "all wax containers. _ __ __________ _ A final word of caution bears upon the use of carbon tetrachloride as a wax solvent. Obviously this compound adds readily to the toxicity of the highly chlorinated waxes. If carbon tetrachloride is used, ventilation should be excellent, but in our opinion it would be better to dispense with car-' bon tetrachloride and depend! on other solvents, especially upon those con taining no chlorine. - - ... BIBLIOGRAPHY Coc-etois-Scffit: Etude sur Fintoxication professionnelle par le trichloronaphtalene. Ann. ce m6d. legale, 14, 422 (1934). Abstr. of paper by Tocraike, - A., axd MAvetrel, B.: Dermatoses professionnelles par la naphtaline et aea derives. Prat. mSd. franq., IS, 335 (1934). Puiior, F. B., ajtd Jabytk, N. E.: Action of certain chlorinated naphthalenes on the liver. Proc. Soc. Exper. Biol. <fc Med., 118 (1936)................ ' K. B.: Kurzes Lehrbuch der Arbeits- und Gewerbehvgiene. S. Hir- '-.:r- *el, Leipzig, 1919 (p. 251). Mittelstabt, 0.: Gewerbeschadigungen durch Haftax (Trichlomaphthalin). Inaug. dissert., Jena, 1935. Tebbens, B. D.: Portable combustion ap paratus for field determinations of .. chlorinated hydrocarbons. This J., 19, 204 (1937). Telekt, L.: Die Pernakrankheit (Chloracne). Klin. Wchnschr., 6, 897 (1927). TotntaixE, A., Solexte, Mn-_tbel, B., axd Acbrun: Cinquante-quatre cas de dermatites par trichloronaphtaline. " Bull. Soc. dermat. et syph., 41, 265 (1984). 300 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [5eL 1SS7 fol. IS, no. 7] EFF Drsccssiox Dr. Cecil K. Drinker: We have had quite a long morning, but since Dr. von Oettingen has to leave, I am going to ask him to say a word. Dr. W. F. von Oet^ingen (Director, Haskell Laboratory of Industrial Toxicol- gy, Wilmington, Delaware): I wish to con gratulate Dr. Drinker and his grour on the very interesting and excellent work on the subject. I also wish to congratulate the Huiowax Corporation on the fact that they didn't spare any effort to elucidate the prob lem so that the dangers which apparently are connected with the use of this material can be controlled. - I personally believe that there is no toxic material which cannot be used safely if it is handled properly. In order to handle such materials properly during the different oper ations it is absolutely essential to be famil iar with the toxicity and especially with the mechanism of the action. Since there is no animal which corresponds in all its physio logical characteristics to the human being - it is important that such compounds be studied with different species of animals so that one can get a cross-section of the poten tial dangers. ~ "" In addition, this fact illustrates the im portance of the pre-employment and peri odical examination of workers in such work. As was pointed out by Dr. Drinker, there are individuals who are apparently more susceptible to certain toxic agents than others. On the other hand, we have to try to detect the'very first signs of incipient poisoning in order to prevent more serious damage. In the present instance it is very difficult to find these very first symptoms because there are no adequate methods, but I trust that in time the scientific profession will supply the medical profession with adequate methods which will allow the physician to determine incipient damage of the organ before serious clinical symptoms become manifest. Thank you. Afternoon Setsion Dr. Cecil K. Dreneer: In this discus sion I will call on one or two individuals and I shall expect others to speak as their notes incline them to. First of all I shall ask Dr, Fayers if he will open the discussion for us. Dr. R. R. Savers (Chief, Division of Industrial Hygiene, National Institute of Health, U. S. Public Health Service, Wash ington, D. C.): Dr. Drinker, Ladies and Gentlemen: It gave me a great deal of pleas ure to have the opportunity to listen to the excellent and interesting discussion and presentations made this morning. Dr. Drinker, and I might add, the members of the Halowax Corporation, have discussed this matter with us, as well as the m&nu- " facturers of the diphenyls. We have been doing some work but not nearly as extensive as that carried on here. The work that we have been doing seems to confirm the work '.hat Dr. Drinker has car ried on. I think there are certain parts of it that we can very well keep in mind. We are dealing with toxic substances, but we are dealing with toxic substances each . .. and every day in industry--harmful sub-.._ stances, hazardous substances. That these can be controlled is well known, no matter what they are, and that we can use them and _ use them in a Bafe manner. Dr. Drinker has called your attention to the fact that , this apparently has been done and can be done in any of the plants w .ere halowax u nX used. I have information from one or two --t; of the other mer who are in the audience that in plants wr.ere damage has been oon* .vVy --skin damage and apparently liver damaS* Xyto some of the workers--the manufacturers ~r-_ have since corrected the conditions and &P" parentlv have adequate engineering con trol supplemented with adequate medical control, _ . .... After all, the proof of the pudding i* 'St-- the eating. If the man does not get the ease your engineering control is successitu-jy.vc If he does get the disease, no matter you have done in the way of engmeerinfcrgypi you haven't been successful. We mu* hand in hand. Neither profession can be successful. We have got to together whether we like it or not. I *SE:- pen to like it. There is one other thing. As far as 'r rials are concerned I think we ougDt to ** ^.v M ceasfuliv. u trni ma adapted tor a certain p it. Another material vious to this for insula was flammable, c&usei approximately 167 me aav approximately 16', Dever just sure whetii It might have been < ne were quite sure that 16 happened when they h with this material. T eieetric cable. It wa. armor on the outside, and was being lowered. proximately 3000 feet to a steel rope. It sli bottom of me shaft. inspecting it he set it i me eapdarap. The ea tne fire killed those me mine. Many of course Here we have one hi Now we have another < due to the toxic mat! evaluate them. Certai I am informed, are als not just sure how fiam flammability probably ehlorination increases, also increases as vot creases, according to 1 think that checks with Lave these hazards to ' control them. I feel c we can. Perhaps we can find o' are better even than th: present time I am adv,< Letter. I am advised t; auomarines, it is quite i aoo-fiammable subszanc their electrical wire. X Os.. Cecil K. Drlnke care to say a word? skP ^** Albert S. Grat fif Occupational Diseas - Department of Oonn.): Dr. Drinker, 11 p-f **JTning that I can say < material in Conrtec: 0002'i tV ' WATER_PCB-SD0000032487 vol. 19, no. 7) EFFECTS OF CHLORINATED HYDROCARBONS 301 smart enough to use every one of them suc cessfully. If this material is particularly adapted for a certain purpose we should use it. Another material that was used pre vious to this for insulation purposes, which was flammable, caused a disaster in which approximately 167 men lost their lives. I say approximately 167 because they were never just sure whether it was 167 or 168. It might have been one or two more but they were quite sure that 167 lost their lives. It happened when they had insulated a cable with this material. They had an armored electric cable. It was covered with lead armor on the outside. It was 1200 feet long and was being lowered into a mine shaft ap proximately 3000 feet deep. It was lashed to a steel rope. It slipped and fell to the bottom of the shaft. When the foreman was inspecting it he set it on fire with his car bide cap-lamp. The carbon monoxide from the fire killed those men that were in that mine. Many of course escaped. Here we have one hazard, a fire hazard. Now we have another one, a health hazard due to the toxic materials. We have to evaluate them. Certain of these materials, I am informed, are also flammable. I am not just sure how flammable they are but flammability probably decreases as your chlorination increases. But your toxicity also increases as your chlorination in creases, according to Dr. Drinker, and I think that checks with other findings. We have these hazards to balance but we can control them. I feel quite confident that we can. Perhaps we can find other substances that *ce better even than this material. At the present time I am advised that we have no better. I am advised that in ships, such as submarines, it is quite important to have a Poo-flammable substance for the insulation f their electrical wire. Dt-. Cecil K. Drinker: Dr. Gray, would yu care to say a word? Albert S. Grat (Director, Bureau Occupational Diseases, State of Conk^ficut Department of Health, Hartford, Dr. Drinker, I don't think there is ^ything that I can say except that we used material in Connecticut and we had a number of so-called cases. All I can say is a confession of ignorance on our part at that time and I was very glad to see that your digging into the literature as thoroughly as you have hasn't elicited any further infor mation than we were able to g"t, basically. About all we could find was t >out the two cats that our friend, Lehmann, experi mented with. We got in touch with him and he confessed that the amount that he had given the cats and his method of determin ing it were probably subject to very serious scientific criticism, and we agreed with him on that point. * We felt, and 1 am very glad that it is what you feel as a result of your experiments, that if we put in an efficient ventilation sys tem sufficient to prevent the dermatitis, we probably wouldn't have liver carnage. That is what we did entirely empirically. I think that is about alt I have to say. I have been delighted to be here and to have as many members of my staff here as I could jack out of the office. We have been de- lignted to listen to the discussion. Dr. Cecil K. Drinker: May we now make the discussion general and those who have questions please volunteer. Mr. Manfred Bowditch (Director, Division of Occupational Hygiene, Massa chusetts Department of Labor and Indus tries, Boston, Mass.): I would like to second very strongly what Dr. Sayers has said with regard to the approach to this problem in proper control rather than by prohibition, which seems to me wholly unnecessary not only in this case but in the case of other toxic substances with which we have to deal. The problem of proper ventilation seems to me relatively simple irom what I have heard of the situation thus iar. The problem of maintaining that ventilation properly does not seem to me quite so simple. I think it is going to be quite necessary' that there should be a very adequate inspection of the plants using tht materials and I can assure you that that will be the case here in Massachusetts. When this trouble first broke in this state a little over a year ago we issued a quite strongly worded warning letter to all plants using these substances and it has all along H{, V i *V m II ib m E :<?j5 [Sept. 1937 been mv plan to follow that up with a fur ther letter bringing the situation as we now know it, aa a result of Dr. Drinker's work, to the attention of users in this state. In that letter we shall unquestionably advo cate the concentrations that Dr. Drinker has suggested this morning. One point that I think is worth comment ing on in that connection is the question of identification of the substances. It is ex tremely important from the state adminis trative point of view that employers using these substances should know what they are using. They are identified at present only b,, numbers. If we list those numbers m a warning letter which we send out there are likely to be changes in those numbers. The Ealowax Corporation is a progressive con cern and it is going to be putting out bigger and better halowaxes all the time. Tbe company's cooperation in this present inves tigation has been such that I feel assured that they will take the proper steps to see that we in the state offices and also the users of the products will know what we are using. I wonder whether Mr. Brown would care to say anything about that. Ms. Sautdford Brown (President, Ealo wax Corporation, New York, X. Y.): There are some aspects of this situation on which I think I can enlighten the medical and state and civic authorities, with respect to the commercial and practical aspects. If you go into the research laboratories of any large chemical manufacturing company today you will find anything from one to a thousand different new chemical products which have not yet been put on the market. Some of those may or may not be toxic. The problem so far as the chemical manu facturer is concerned is a question of timing. You have heard this excellent presentation given this morning by the Drinker brothers as to the work that they have done here. Should you take a product of which you have developed, say. 5 or 10 gm. and spend 550,000 on research to determine whether or not it is toxic or should you wait unti you have determined whether you have a rm.-ket for it? If you are producing only one hundred substances a year you can see that that would run into boxcar numbers in the way of dollars and cents before you ever sold any. That is the problem we have had in this case. It has been on the market for 25 years. Until within the past 4 or 5 years there has never been any intimation that it would cause any systemic effects. Thou sands and thousands of workmen have dealt with millions and millions of pounds of cer tain of these materials, particularly the tri- chlornaphthalenes. Then we come to the higher stages, combined with chlorinated diphenyl and other products, and suddenly this problem is presented to us. We had asked various authorities in terested in public health, going back over a period of 15 to 20 years, to investigate it but there wasn't much enthusiasm for it. Mr. Bowditch suggested that we take it up with the Drinker brothers at this institu tion, which we did. You know the results of that work. Xow so far as these changes are con cerned, they are beyond our control to a certain extent. We will manufacture a product--let's call it 1254. It has certain chemical and physical characteristics. It is supplied to a cable manufacturer. It is composed of certain constituents. There may be some tetrachlornaphthalene, tri- chiornaphthalene, paraffin, a little pitch or bitumen, and possibly some chlorinated diphenyl. It does a certain job but he wants it to a little more plastic or he wants its viscosity or the specific gravity changed. Possibly by a change in those constituent* of only 1 per cent we can get that particular property. We can't sell it to him as tbe same product so we put a new number on )t- Basically, however, if the variation in the chlorinated naphthalene or the chlorinated diphenyl constituent hasn't changed, the toxic property of that will not change. When it comes to a question of cooperat ing with the state authorities in that con nection, if there were some major change made in a product we would have no beattan cv in advising them and we would al* advise our customers. Virtually every con sumer of these materials at some time f another has been given their technical of chemical designation along with their v*iV ous properties, whether they be physical of - chemical. ' Those are some of the practical problem* . pof. 19, no. 7J with which all i t. synthetic organ mer. t is so rapid can t even keep i g. menu sometime; doing. V5W Vy -Sc: life. vy. -'AT'/ Mr. F. R. k aP-.*, York Wire* ^ ork, Ra.): I an this opportunity reference to the our York plant. again in this case the best teacher problem tt Yori through the expe It is only 1 j ye neighborhood of. various degrees oi air know. Eight severely affiicteda* their skin cond man died and the < uted his death vapors but we an as an atrophied c of the autopsy- bui that it was or wa wrk. Knowing employed, wit tion that he had, *hin, pallid in his not say from my physical make-up he presented a hei ever. it was only fc `he tune of his' ei plained of this coni vised that he see fapidly developed `he hospital anc tied. W&jz-Z-- More serious tha: we had 50 othe 7 M far as the a< f*.1 faction that ( ^^to throw ; They dies T*`[or bating wi b` not so easi veil have thrown and said, "V 0002G WATER PCB-SD0000032489  - b" s'--**? <5 '.S' .i :em* -- 19, no. 7] EFFECTS OF CHLORINATED HYDROCARBONS n-ith which all manufacturers of chemicals are confronted today, particularly in the synthetic organic field where the develop ment is so rapid that our 3aies departments can't even keep up with the research depart ments sometimes, in knowing what they are doing. Me. F. R. K.vimer .Assistant to Manaeer, York Wireworks, General Electric Co., York, Pa.): I am certainly pleaded to have this opportunity to say a few words with reference to the "xperience we have had at our York plant. I perhaps should say that again in this case experience alone has been the best teacher. I have lived with the problem at York with the men who went through the experience from its beginning. It is only lj years ago that we had in the neighborhood of 50 to 00 men afflicted with various degrees of this acne about which you all know. Eight or ten of them were very severely afflicted--horrible specimens as far as their skin condition was concerned. One man o led and the diagnosis may have attrib uted nis death to exposure to halowax vapors but we are not sure of that. There was an atrophied condition found as a result of the autopsy but we are not definitely sure that it was or was not connected with his work. Knowing the man as I did when he was employed, with the superficial examina tion that he had. he appeared to me very thin, pallid in his appearance, and I would not Bay from my poor knowledge of the physical make-up of the human being that he presented a healthy appearance. How ever, it was only for a 6 months' period from the time of his employment that he com plained of this constipated condition and we advised that he see his home physician. It rapidly developed to the point where he was the hospital and in a very short time he died. * _ ^re serious than that perhaps is the fact tha-t we had 50 other men in very bad condi- rE as far as the acne was concerned. The "at reaction that several of our executives ad was to throw it out--get it out of our They didn't want anything like .1 ^or treating wire. But that was easily hut not so easily done. We might just well have thrown ou- business to the four and "We'll close up," because there was no substitute and there is none today in spite of all the efforts we have made through our own research laboratories to find one. But we did develop--and I j most closely associated with it--and set up a routine for bringing these men back to nor mal health conditions. A number of them were sent to Dr. John H. Stokes and to Dr. 0. H. Perry Pepper of the University of Pennsylvania Hospital, and the others to Dr. Isaac R. Pels at Johns Hopkins. Through their recommendations and studies we employed a trained nurse and two local physicians and you might say established a small hospital and its facilities at the plant. Through the application of quartz light, x-ray, mechanical removal of comedones and the treatment of pustules that de veloped in later stages, an utterly strict routine where the worst cases were adminis tered to each day for a period of 15 to 20 minutes, another group who were less seri ous three times a week, and still another group once a week, we have in this year and a half brought each and every man back to a normal skin condition. Those who were very seriously afflicted do show scars, but otherwise their skin is as healthy in appear ance as my own. I tell you we are very proud of the fact that they are still all em ployed and the amount of halowax that we are using today is even greater in quantity and in types than we were using a year and a half ago. . With the adequate ventilation system we have installed, with the routine for change of clothing from street clothing to work clothing when they come to work and the reverse of that process, with the assurance that a Bhower will be taken before the street clothing is again put on, we have found no recurrence of this skin trouble. Each and every man working with halowax products, either from, solution, from solid compounds or handling the wire insulated and treated with it, is examined twice yearly with a com plete physical examination, including blood analysis and efforts to determine any liver damage. However, there is the point which was . very definitely brought out this morning. We do not know as yet when this thing starts. I believe it would be c: great help - - Mi St "SB? u sir :"r( i Sif-lpa ayv.i-n tv r^ s-- emmi 000211-:; up WATER PCB-SD0000032490 304 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY {Sept. !9S7 to ua all in Industry if Borne very funda mental work was done on humans, as Dr. Jones mentioned beiore we came into this meeting, some control in fundamental work to determine some method whereby we may determine the inception of any liver dis order. We have had our men examined in groups three times since the trouble developed and nothing has shown up in any one man. We have learned and appreciate the fact that we must handle hazardous mate-inis, but we have learned how to handle tnem. It has been a very great experience for us and for myself, and again the best teacher. Da. Cecil K. Drinker: Can you recol lect the air concentration that you are main taining now with your present ventilating equipment? Mr. F. R. Kaimer: We have had two examinations made of the air by Mr. Wil liam F. Kemperly and they average from 0.2 to 0.6 mgm. per cu. m. We recently dis covered one condition which was found as the cause of a high reading In one of the examinations. The compound is one that is not manufactured by the Ealowax Cor poration that is used rather infrequently, perhaps not more than 50 gallons of it in a 6 month period. It Is in the form of a paste, reduced with solvent to a paste form, and it was not known that it contained-a chlorin ated solvent in certain percentage. We dis covered it only recently through the analy sis of a sample and we found that that was the cause of throwing the results off to a hig'- value. It was then about S mgm. per cu. m,, I believe. That is going to be eliminated now. That is a combination of toluene and carbon tetrachloride solvent. When that compound is exposed to the air the chlorin ated solvent odor is completely masked by the toluene. It *s lost. I was able to detect it only by removing the head of the drum and immediately smelling the odor of carbon tetrachloride. As soon as that head was removed for a period of 10 seconds the tolu ene predominated and we had no knowledge of the other being in there. _ Mr. Arthur G. Beter (Research Engi neer, United American Bosch Corporation, Springfield, Mass.): Do I understand you to say that those men who were afflicted are back on the same job? Mr. F. R. Kaimer: They all returned to normal skin health, as I say, and are working on the same job. Dr. Cecil K. Drinker: Dr. Schwartz, you ha-, e seen a good deal of this general subject. Dr, Locis Schwartz (Medical Director, Dermatoses Investigations, United States Public Health Service, New York, N.Y.): I am primarily interested in dermatitis and it was only because of my researches in that field that I happened to come across infor mation given to me by Dr. Gray that there were some cases of yellow atrophy of the liver attributed to halowax. I can only talk from personal experience about the skin cases. I know from what I have seen and from what I have heard from doctors who have been treating these cases that if they are treated like an ordinary acne vulgaris and kept away from further large exposure they all get well, with the same results as acne vulgaris. Those who have large pus tules may have scars resulting and those who have superficial pustules or only come dones won't have any scars. As far as prevention goes, I felt even be fore this investigation was undertaken that this substance, like any other poisonous substance, can be handled and used in in dustry provided proper safety precautions are taken, and I so advocated at the meeting in Pennsylvania when this was discussed. About ventilation and safety precau tions, I think that while we cannot, with our present knowledge, detect by any chemical tests the early symptoms of intoxication from thus substance, the skin offers an easy way of proving whether your method of ventilation is efficient or not. If there art any cases of acne or of this dermatitis occur ring in a plant where halowax or the chlorin ated naphthalene or chlorinated diphe0?*4 1 are used, then that shows that there is st3j` ' ficient concentration of these substances J the air to cause plugging of the follicle to cause a skin condition. If there is suffi- cient concentration to do that there noa.v ^ j3J. Et fjt;. __ _ ^ vol. 19, no. -f ILL sufficient concentration t poisoning in the few peopi sensitive to the action r,f bons. Everybody is not them. If they were, of ' people who have been hai stances, more would hav< disease and it would ba\ very much earlier. This r in Germany as early as 19 While I cannot add methods outlined here for of ventilation and so fort! if you go into & plant ar any acne present among this material you will kn sufficient of the substance : acne and consequently sufi be dangerous to the lew hypersensitive to its actio Dr. Cecil K. Drinker tical point in regard to the - mining these substances in pointed out this morr.inj several pieces of apparatt It has seemed desirable to men who are here that dur pie of years, while we are learning, that we endeavt confine our analyses to or ratus, so that at least our comparable as we can makf to place. . . ~ I don't know much abo the subject: perhaps, Mr. an idea or two about that. Mr. Warren A. Cook < Hygienist, Bureau of Oc CA-aes, State of Connecticu Health, Hartford, Conn.) sda&tioa of the halowax 'wouldn't be preferable to J*':y discuss the method c throughout the country fu tion of chlorinated naphti 1 Ea. Cecil K. Drinker '-c-t is concerned it is b discussions with Mr. Hi Hrxndt afterward. But determining some uniform! -bile s.-_ ;eas- jSj j think. **** "terest to us. 00023 WATER_PCB-SD0000032491 vol. 19, no. effects of chlorinated hydrocarbons tc J! A sufficient concentration to cause systemic poisoning in the few people who are hyper sensitive to the action of these hvdrocar- bona. Everybody ia not hypersensitive to them. If they wre, of the thousands of people who have been handling these sub stances, more would have contracted this disease and it would navi been reported very much earlier. This material was used in Germany as early as 1914 or 1915. While I cannot add anything to the methods outlined here for safety in the way of ventilation and so forth, I can say that if you go into a plant and find that there ia any acne present among the workers with this material you will know that there is, sufficient of the substance in the air to cause sene and consequently sufficient perhapB to be dangerous to the few people who are hypersensitive to its action. Dr. Cecil K. Drinker: There is a prac tical point in regard to the question of deter mining these substances in air. My brother pointed out this morning that there are several pieces of apparatus for doing this. It has seemed desirable to a number of the men who are here that during the next cou ple of years, while we are in a position of learning, that we endeavor, if we can, to confine our analyses to one piece of appa ratus, so that at least our results will be as comparable as we can make them from place to place.- " I don't know much about this phase of the subject: perhaps, Mr. Cook, you have so idea or two about that. - Mr. Warren A. Cook (Chief Industrial Hygienist, Bureau of Occupational Dis eases, State of Connecticut Department of Health, Hartford, Conn.). On the deter mination of the halowax I wonder if it wouldn't be preierable to have Mr. Hemdiscuss tne method he has been using oroughout the countin' for the determinakon of chlorinated naphthalenes. Cecil K. Drinker: I think so far that is concerned it is best to leave that discussions with Mr. Eemperiy and Dr. . randt afterward. But the question of tetrmining some uniformity of technic for & "mile at least is, I think, a matter of gen- interest to us. Mb. Warren A. Cook: I am not quite sure that I have in mind exactly what you want in that regard. In connection with sampling? Dr. Cecil K. Drinker: Yes, In con nection with the whole technic of determin ing the materia! in air, length of sampling, type of apparatus, and so forth. It has been suggested that wp endeavor to agree upon some uniform procedure for that and as figures begin to come in. as they v.l in the course of `he next couple of year1;, we will at least nave them on % comparable basis. Mr. Warren A. Cook: In that regard there is no question but what the determina tions and results of analyses of the concen tration of injurious materials in air, corre lated with pathological findings or freedom from pathological findings, arc real factors in further substantiating toxic limits which are originally given us from animal experi mentation. In order to obtain data which are of value along that line it is desirable to know to what extent, in terms of milligrams per cubic meter, workers are exposed to in breathing any potentially injurious material. It seems to me that one of the things that should be done, which many of the plants and man}- of the organizations equipped to make determinations of injurious materials in air should do, is to make an effort to develop one group and series of results which will represent average exposures of workers to chlorinated naphthalenes. In getting that figure I think that it is of great importance that we should consider average daily exposure. There is a tendency very often in taking samples of air to determine maximum exposures, to get the exposure over a 15 or 20 minute period when the worker may be actually tending a pot where the material is being used, whereas during the subsequent half hour he may be 40 or 50 feet away from that particular location. Therefore, for one thing, it seems to me it would be extremely desirable to obtain in formation in as many plants and as many locations as possible of the average expo sure, taking into consideration not only the worker's maximum exposure whiie actually YUisiWMfl .flips : -f-if 'y iffcsjS? SL'Z=i.tjCsz-i* i.'j; . 00023 WATER PCB-SD0000032492 306 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY (Sept. 1957 at work vrith these materials but also his much smaller exposure and possibly even lark of exposure as he may go to other parts of the room or even to other departments during the course of the day. Another type of determination which seems to be extremely desirable to have is concentrations of the chlorinated naph thalenes at certain reference points. I believe that Mr. Hemperly very carefully duplicated these reference points in each of the plants where he took his determina tions. He took the samples, I believe, at breathing level and a certain measured dis tance from the pots where the chlorinated naphthalenes were being handled, so that next year he could go back to those same locations or others could take determina tions at those same locations, which are definitely fixed and recorded, and learn whether, due perhaps to clogged pipe lines or to fans which might become loaded with the condensed chlorinated naphthalene, there might be poorer ventilation than origi nally designed and higher concentrations of the chlorinated naphthalene than origi nally determined. It seems to me that it would be an ex tremely desirable thing to have made avail able for all of us who are making these determinations these reference points bo that L~. Massachusetts and in Connecticut, at one plant or at another, a considerable group of workers could be taking samples at this one particular point with reference to the Bource of generation of the vapor. Such results would permit a comparison of knowl edge between plants. In that regard it happens that there is a committee of the American Public Health Association which is charged with the devel opment of chemical methods for determina tion of atmospheric contamination such as that now under consideration. It seems to me that it might be a very desirable project for that committee to consult with the in vestigator of the Halowax Corporation and suggest to all of those who are doing work of this type, after some discussion, what reference points could be adopted and also what should be done in connection with get ting these average exposures. Asa matter of fact our committee will discuss that very feature and possibly include it in our report before the A. P. H. A. in October as one of the projects which we shall carry out at that time. As I nave not given this consideration. I am afraid my discussion is not as connected as I might wish it to he. We have a ral problem here and one that deserves some study. Dr. Cecil K. Drinker: Would it be of service to the American Public Health Asso ciation Committee if a sub-committee from this meeting, collected perhaps by my brother and those of you involveu with these problems, were to make a recommendation to the A. P. H. A. as to the things you have brought up and as to suitable apparatus, and let the final statement come from the Association after they have considered that material? Mr. Warren A. Cook: I think that would be a splendid idea because we have a bulk of information on this particular material. A number of individuals hare given much thought to the development of apparatus, both the combustion method which we have here and also the continuous record type of apparatus which Professor Drinker mentioned this morning. I think that it is a sufficiently important project that a sub-committee made up from this group could give that committee a very definite steer. [Personnel of the Sub-committee: W. A. Cook, chairman, A. L. Coleman, H. B. El kins, W, B. Fulton, S. W. Gurney, E. RHavhurst, W. F. Hemperly, F. W. Sehl, and A. N. Setteriind.j Mr. Kertet B. Elkins (Chemist, Divi sion of Occupational Hygiene. Massachu setts State Department of Labor and Indus tries, Boston, Mass.): In connection wito what Dr. Schwartz has said, I am not sure that I am in complete agreement as regards the use of skin lesions as warning agents. It is my understanding that in insulated wire plants the chlorinated diphenyls are very commonly compounded with the chlo rinated naphthalenes. It is also my under standing that these are more likely to cause a severe skin irritation than the straight chlorinated naphthalenes. On the otnr fof. 19, no. ELI hand, from Dr. Drinker's pidge that the straight `'1 tbaiene was nearly as tox: mixture of it with s srr.a" rinated diphenyl. PA In the condenser fact, our cases there is no chi*, used and no acne of the t the reports on the insulate Dr. Pv. Emmett Kelly ical Co.. St. Louis. Mo.]: i anything to th- laboratory has b*en quite a little hurr tion in the last several ye: our plants where we have i; inn this chlorinated diphe: ou observation that altho si> : we did have a more senes of skin eruptions whi ti/R to attribute as to caus ur.Rarity in the benzene w* the chlorinated diphenyl, a any systemic reactions at Re have examined them \ from what laboratory te might help us and from t point. Also from chi or alone there have been no < poisoning reported. I don't believe that we t laboratory results into th without paying considers the volatility of different sc way they are being used. De. John A. Hooket ( matologist, Kalowax Corp Mich.): I have had consia with the dermatological a: lem. The experience at i: at Wyandotte definitely vs 'l "tis did increase when ^*1 rather than the strt naphthalenes. From the discussion ve J think the observation D ^tat the chances are tha ProDlems will disappear ak Probably true. Howev Attain, precautions, certak lL'ai yr . mieht say, she men who are gou 'nese products, even thou 00030 WATER_PCB-SD0000032493 vol. 19, no. n EFFECTS OF CHLORINATED HYDROCARBONS 307 hand, from Dr. Drinker's work one would judge that the straight chlorinated naph thalene was nearly aa toxic at Dast as the mixture of it with a small amount of chlo rinated diphenyl. In the condenser factory where we had our cases there is no chlorinated diphenyl used and no acme of the type described in the reports on the insulated wire factories. Dr. R. Emmett Kellt fMonsanto Chem ical Co., St. LouL, Mo.): I can't contribute anythim: to the laboratory studies but there has beer, quite a little human experimenta tion in the last several years, especially at our p;:::Us where we have been manufactur ing this chlorinated diphenyl. It has been our observation that although on one occa sion we did have a more or less extensive series of skin eruptions which we were never able to attribute as to cause, whether it was impurity in the benzene we were using or to the chlorinated diphenyl, we have never had any systemic reactions at all in our men. We have examined them very closely both from what laboratory tests we thought might help us and from the clinical view point. Also from chlorinated diphenyl alone there have been no cases of systemic poisoning reported. ' I don't believe that we can transpose the laboratory results into the actus: humans without paying considerable attention to the volatility of different substances and the way they are being used. Ds. John A. Hooket (Consulting Der matologist, Halowax Corporation, Detroit, Mich.): I have had considerable experience with the dermatological angle of this prob lem. The experience at the Haiowax plant &t Wyandotte definitely was that the derma- tsie did increase when compounds were ^d rather than the straignt chlorinated Dlpfathalenes. From the discussion we have heard today ^ think the observation Dr. Drinker made **mt the chances are that dermatological Problems will disappear along with the other ** Probably true. However, I think that ^rtain precautions, certain insurance meas^re*i you might say, should be taken in hiri men who are going to work with th products, even though we are going to at'cmpt to g`t the concentrations low. We saw this morning that the effect of these products was on the liver and that if some one working in these products deveior-'d liver damage from some other source tne chances of his having serious trouble was increased. Therefore, inasmuch as there is no test to tell whether a person has had liver disease, certainly in the preliminary medical examination of applicants for work the his tory at least should be gone into very rarefully for a history of previous liver diseases. '. here are other things that svjuld he taken into consideration also. On is the history of syphilis, because syphilis does have an effect on the liver. If there is any history of syphilis I don't think that that man should be hired, A Kahn test should be taken and I think that it would be a good plan to take Kahn tests on men at staled intervals, because they might develop syphilis after they are hired. I think those things should be doDe even though we feel that if the concentration of these vapors in the air is kept as low as was recommended this morning, the chances of having toxic effects are very small. Mr. F. R. Kaimer: I would like to clarify a point of Dr. Hookey's. You mentioned at the beginning of your talk that vour experience in acne condition was more pronounced from the compounds of various materials with chioronaphthalene than with the straight chloronaphthalenes. Did you mean by that, that the acne condi tion actually was more pronounced with the compounds than with the straight chioro naphthalene or was thatdue to the fact that you were in a plant operated in a different fashion? In other words, you handled your numerous wire compounds in more of a batch operation. That is my understand ing from Mr. brown. Is it a fact that the straight chloronaph thalenes are less harmful in so far as acne is concerned cr is it because ' the handling of batch compounds? Dr.. John- A. Hookey: That is a question that would be difficult to answer. . I based my statement on the fact that in taking a general survey of these cases after I started working with them the men in the piant said 30S JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [Scpl. I9H7 that they developed acn< more often and more severely after they started making compounds. It may be that it was in the method of the handling. Mr. F. R. Kaimer: You say that the con dition increases with the increased chlorine content and we arc attributing the acne pri marily to the chlorine radical. If that is true, what are we to associate insofar as these various other constituents arc con cerned. such as various plasticizing agents? How much do we know about those insofar ^as development of acne is concerned? Some of these compounds have a half dozen con stituents in them other than chlorodiphenvl and chloronaphthaiene. We are at the present time considering the chloronaphtlialene as the basic element responsible for the acne condition which we have. We know very little about what the other mate rials may or may not do. Dr. Joh.v A. Hooket: I don't know about these other materials. Perhaps Dr. Schwartz would know something more about them. Dr. Locis Schwartz: It is well known in industry that there are many compounds that cause acne. For instance, paraffin acnes and oil acnes have been known for a long time. Paraffin acnes, wax acnes, are simply a mechanical plugging of the fol licles of the skin by the minute particles of wax that fall on the skin. I think that the acne caused by these chlorinated naph thalenes and diphenyls, because it is caused by both--I was down at the Swan Chemical Company where they make chlorinated di phenyls and they have acne there just the same as over at Wyandotte where they make the chlorinated naphthalenes--I believe that that is caused by the same thing, a blocking up of the follicles of the skin, the formation of the comedone and th-.m the comedone becomes infected and forms a pustule. They don't all pustulate because they don't all be-. :me infected. Many of these men never have any- pustules. They just have littie white elevations on their skin. In those people who are in the acne age, the youngsters of IS, 20, 22 and 23, acne vulgaris is most apt to occur. The sebace ous gianda are most active and they seem to have it mn.-h more than the --Ider people m whom the sebaceous gianas are not so active. We keep a clipping of all articles relating to industrial dermatitis in my office and 1 recently read an article in a German maga zine in which they report in Germany a similar acne condition from chlorinated pi .ols and chlorinated benzenes and solid waxes, it seems that this acne-like condi tion is not peculiar to hulowax or chlorin ated naphthalenes or diplv. nyjs but can occur with any condition that blocks up the sebaceous follicles of the skin. Dr. Rotal Meeker fSpecial- Agent, State of Connecticut Department of Labor, Hartford, Conn.): I am full of questions. As a statistician I am a littie bit suspicious of averages, so I should think that we should take maxima as well as averages in getting at the threshold dose or the dangerous.im pregnation of the atmosphere with these poisonous compounds. I just want'd to drop that as a hint for this committee to consider in its work. In spite of wuat you said at luncheon, Dr. Drinker, I still think it is rather impor tant to determine how the plugging of the pores actually does occur, whether they are plugged as Dr. Schwartz has suggested, from the particles falling on the outside of the skin or whether they are plugged, as so many doctors have informed me. from inside as it were. The fumes are breathed, tae substance gets into the blood stream. It is thrown off through the pores of the skin and the pores are plugged. I think it is rather important to determin-: that because it seems tome, from the slight knowledge that I have of the industrial application of ha!ows:. compounds in insulating wires, that the plugging of the skin, if it is just an out side plugging, may take place either fro handling a solid substance or from the coating on the wire after it becomes cold. I haven't heard anybody say anytninS about those Massachusetts cases of very severe dermatitis and I am not bo sure but what there was some question of liver dam age there. Nobodv has said ar.vthing about them at all. There is no question tnere M. n,l. 19. no. 7\ EFFE that the conditior., v.!.a tions might have been, i ccld wire, in a cciifiin ! think this needs a grt Dr. Drinker, than you ; have been able to give -. curiom about is the way the protective iubur law* both the employer and tl I listened with very g expositions of sugcestec cation of nalowax. chlur and diphenyl, k seemf left very much to be ae why the application of pound, if it is necessary to use thiB rather dangero t>e done in a practically < please. Dr. Drinker, I w Mr. Reeves of the R.01 Corporation to tell how it. If I am any judge safety devices they havi eliminating entirely frot all contamination from ft rated nalowax as anyone, cation of halowax, either or where it is applied to under hooding and with ratus, and it seems to be Mr. E. E. Reeves 0 General Manager, Ro-.i Corporation, New Have:, very; glad to tell of 0U-- e: help the picture along. C been more or less parallel in as much as we manufac: ci wire. We have avoiae lure that he ran into, pr< fact that shortly after 1= benzene as a solvent for a; W got into anemia dir. 2-: - fumes and had to i vem.iiating system, to r lumes from the machines compounds to the wire installation of that equipr 10 a substitute (or ben ut of the picture. ^"e are still in the sam< ^sc is as far as finding a su *'a*. There is none that v tequentiy when we went t- T.lf .it:;' fHBfe 00032 '....................... WATER PCB-SD0000032495 ru!. 19, nu. EFFECTS OF CHLORINATED HYDROCARBONS 309 that the condition, whatever the complica wax we had a head start as far as the tions might have been, came from handling ventilating system was concerned, since cold wire, in a confined area of course. ours was aireadv installed and selectable to I think this needs a great deal more study, a compound with a benzene sc rather Dr, Drinker, than you and your associates than a melted naiowax compound In order have been able to give it as yet. All I am to keep the fumes of a highly volatile sol curious about is the way we can administer vent under control we did develop a prac the protective labor laws in order to protect tically complete enclosure for the container both the employer and the employee. in which the compound was placed and I listened with very great interest to the exhausted that container in order to prevent expositions of suggested pots for the appli any escape of the fumes from it. Wnen wc cation of he. wax, chlorinated naphthalene ciianged to the halowax compounds we fol and diphenyl. It seemed to me that they lowed the same scheme of applying the left very much to be desired. I don't see compounds and used a completely enclosed why tht application of the halowax com pot. There is a hole in one side for the wire pound, if it is necessary, as I assume it is, to go in and one on the other side for the to use this rather dangerous substance, can't wire to come out. There is enough exhaust Pi be done in a practically closed pot. If you suction on the enclosure to prevent any please, Dr. Drinker, I wish you would ask fumes from getting out of the openings Mr. Reeves of the Rockbestoa Products where the wire enters and leaves. Of course Corporation to tell bow they have handled periodically it is necessary to open the pot it. If I am any.judge of equipment and to replenish the compound or make adjust safety devices they have come as near to ments. In that case we have the ventilat eliminating entirely from the atmosphere ing system interlocked with the door that all contamination from fumigated or evapo the operator opens so that when he opens rated halowax as anyone. All of the appli it he increases the amount of air travel cation cf halowax, either in. the melting pots about ten-fold. or where it is applied to the wire, is done under hooding and with ventilating appa Dr. Royal Meeker: What is the veloc ratus, and it seems to be entirely adequate. ity when the door is open? Mr. B. H. Reeves (Vice-president and General Manager, Rockbestos Products Corporation, New Haven, Conn.): I will be very glad to tell of cur experience if it will help the picture along. Our experience has been mere or less parallel with AD. Kaimer's in as much as we manufacture the same type of wire. We have avoided the serious pic ture that he ran into, probably due to the fact that shortly after 1923 we were using benzene as a solvent for asphaltic materials. We got into anemia difficulties with ben zene fumes and had tc .nstall a compieie ventilating system to remove all those fumes from the machines that applied the compounds to the wire. Following the Htatallation of that equipment we were able 10 ?et a substitute for benzene, so we got it out of the picture. ^"e are still in the same fix as every one efae is as far as finding a substitute for halowax. There is none that we know of. Consequentiv when we went to the use of halo Mr. B. H. Reeves: With the door wide open, at breathing level the velocity is 200 feet. That is the linear velocity. We check that every week on every opening at every machine with a velometer, a small instrument which is easy enough to operate and reads directly. Whenever the velocity falls beiow that figure the pip? connecting that machine is taken down and cleaned, because there v 1 be condensation inside the pipe to cut c-.n-a the air flow and reduce the V'-ntilation efficiency. Dr. Rotal Meeker: What do you think of that trap device shown? Mr. B. H. Reeves: I don't know what to think of that. I don't know whether it would be practical or not. 1 was going to ask Dr. Drinker whether in passing the air laden with halowax fumes through the boxes of rats there was any deposit of haiowax in th; enclosure. ;r>l - Li I i :' j ; Ali.'ji'j.'ithiwA; '.'-I',' 0003.! r" WATER PCB-SD0000032496 i ;-;io JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [Sept. /S.5? col. 19, no. ?! EFFEC Dr. Cecil K. Drinker: Yes. It is complaints were bona Sde. V,'.;. had no dif ry Dr. B. L. Vo?Bfro r : detectable readily through the outflow pipe. ficulty in handling cold wire and the men questions in mind. I had no skin trouble. Yet when they did wtiat Mr. Brown wi>uui ? i Mr. B. H. Reeves: Those in the far end the same thing with possibly the application bihiy of using onlv If rX probably didn't get the concentration. of heat in tunnels, ships and s: Firth, they actually did develop trouble. chi .rinated naphthalene Dr. Cecil K. Drinker: We change the position of the 1 ixes each dnv. The ones furthest away move into the nearest posi tion, so that over a period of weeks all are exposed equally. We have used, of course, the icterus index in following some carbon tetrachloride cases and 1 wondered what you have to say about that. Is that o: no value at all in the case of liver damage in this material? Mr. Sxndford Bro r* simplify our problem exri from the commercial sta the toxicity standpoint. i. 1 think that Mr. Kaime: Dr. Emery R. Hayhchst (Consultant .in Industrial Hygiene. State Department of Dr. Cecil K. Drinker: I don't think so un:il it gets so extreme that we know it any to object because he v. o'.: . 7~* the technical effects he d< Health, Columbus, Ohio): I would like to way. Yf; The same thine applies ' ask if it wouldn't be possible to put a cold industry where we are u water line around that trap and deposit it Dr. B. L Vosbcrgh: I did write down a agr- chlorinated products. all before the air escapes from the trap. few questions that came to mind. Some of M: The problem as we'see them have been answered and some are which we intend to studv Mr. B. H. Reeves: We have tried cool foolish but I shall ask the:: anyhow. our program for this corn ing the surface of the exhaust pipes in order It occurred to me that trichiornaph- will be done under the to concentrate the deposit in cue place and thalene has been proved to be practically make it unnecessary to remove long lengths innocuous, isn't it a problem of research WggA. - Drinker brothers), is to t: demarcation and whether of the ventilating .-"stem. While we have largely for the Halowax Corporation to use complicated chemical s: found a slight advantage in doing so it only that one material adopted with other Borne one thing that cause hasn't at all paid for the expense. It is known chlorinated compounds to meet the we could take bexachicr much easier to take the piping down. Con requirements of customers? That is one remove 1 per cent of some sequently I doubt the possibility of remov of the foolish ones probably, but I shall cent with which we are ing it all by cooling the surfaces of the trap. just ask it. and eliminate the toxicit i It might be possible, by building a labyrinth Furthermore, how long is it reasonable to of refrigerating coils, to collect it. But expect the liver to recover after it has been a lovely solution. Wheth able to attain that I don' then you would have the problem of remov pretty well damaged. I talked to you and one of the things we have ing it from th- coils after you had collected you said you hadn't worked that out with As I said before, that is it and it would involve ratner complicated the animals as yet. procedure. with which all manufactu tbetic organic products s Dr. Cecil K. Drinker: In that case we some stage, either in their Dr. B. L. Vosbttrgh (Medical Director, set aside a certain number of animals to commercial developments General Electric Company, Schenectady, New York): We have heard about the pos sibility of preventing liver damage and skin recover, after knowing that a certain amount of damage had been done. Then we started to kill them but we invariably question of timing as to wi the work, how much vot whether you know how to r&r. trouble among manufacturers of wires and ran out of rais before they ran out of lesions. cables and so forth, but like the old rhyme, We don't know how long it lasts. every dog has fleas and the fleas have fleas, to learn that first. Dr.. Cecil K. Drinks: we aiso have customers who use wires and De. B. L. Vosbergh: Have you given orne other important ms: cables in tunnels, in enclosed spaces, splic them calcium and glucose as you would with toe meeting adjourned. ing them together and doing all sorts of carbon tetrachloride? things. I am not at all certain that we know what ne concentration of these chlorinated hydrocarbons i3 under those conditions. About the time we were having so much trouble at our York factory some of our Dr. Cecil K. Drinker: Not vet, but we are doing an experiment now with one group on a very high calcium diet and another group on a calcium free diet. The whole L>b. R. R. Sxters: M more with regard to what 1 u syphilis? If you are t your workers who ht customers began complaining. We thought question of calcium in the diet, of giving we were having a hysteria of halowax mania milk daily to these people may be worth I$V throughout the country. Some of their while. tvr 00034 ?>.' Hx"'"' `'fU TL^iqvr-- WATER PCB-SD0000032497 vol. 19. TU r] EFFECTS OF CHLORINATED HYDROCARBONS Dr. B. L. Vosbcroh: I just had those syphilis during the time they are working questions in mind. I would like to hear for you, you are probably going to lose some what Mr. Br wn would <ay as to the possi very important employees. It would seem bility of using or.1 this one innocuous that it would be worth while to g-ve serious chlorinated napht:. ne. consideration to seeing that conditions are proper and suitable for them to continue Mr. Sandford Brown-: That would working for you and that thpy have proper simplify our problem exceedingly, not only treatment. In other words, I don't believe from the commercial standpoint but from that is a good or sufficient reason for dis the toxicity standpoint. But if we did so charging those employees who do develop 1 think that Mr. Kaimer won: be the first syphilis. We have not found that to be to object because he wouldn't tit able to cet true in other places and I question whether the technical effects he desires in the cable. The san. thing applies throuchout all the this is one of the places. I may De in error. % industry where we are using these higher Mr. Sandford Brown: I want to take chlonnnted products. this occasion to express on behalf of the a The problem as we see it, and it is one Halowax Corporation my thanks for the which we intend to study further (we have excellent cooperation we have received from re our program for this continuous work that various state authorities and our customers will be done under the direction of the as well in this investigation. I believe you Drinker brothers',1, i8 to try to find a line of have all formed the opinion, based on what y :h demarcation and whether or not within this you have heard this morning, that our whole complicated chemical structure there is motive here is to conduct this on an ethical, se some one thing that causes the trouble. If scientific and constructive basis. er we could take hexachlornaphthalene and In collaboration with the Monsanto je remove 1 per cent of some unknown constit Chemical Company we have a much more ne uent with which we are not now familiar comprehensive program in view to carry on. ill and eliminate the toxicity, that would be Therefore we want to continue that same a lovely solution. Whether we will eve: be type of cooperation. DO able to attain that I don't know. That is There is one thing that I want to bring up en one of the things we have in mind. in that connection, which will have to be id th As I said before, that is one of the things observed by the state authorities, when they with which all manufacturers of these syn go out to make these inspections. That is thetic organic products^ are confronted at the necessity of not- creating mob hysteria some stage, either in their laboratories or in on the part of the workmen in the plants xe commercial developments. It is largely a where these inspections are made. Mr. to Question of timing as to when you s..ould do Kemperiv has run into some very interest tin the work, how much you should do, and ing situations in the various examinations en -iy whether you know how to do it. You have he has made. I know that he would be glad to learn that first. ' to relate them and give the benefit of hiB .is. experience to the heads of any of these state departments who will have the direction of De.. Cecil K. Drinker: Unles.- there is this work. Otherwise I can see where we en other important matter I wili declare will be unable to get the full cooperation of ith ttie meeting adjourned. not only the individual workmen but the piant foremen and the management, and we Dr. R. R. Satep.s: May I say a word must have that if we are to get the results we ore with regard to what Dr. Hookey stated that we are shooting for over the next sev up 0n syphilis? If you are going to eliminate eral months or years. This thing may con ner your workers who happen to develop tinue, probably will continue for years. ole :ag rth A - * W&'ZZSrr h WlSS jfy , v ' <jr * 'T? ' c *J W. sigh* 3m iirr-jr.-rsac. WATER PCB-SD0000032498