Document Oz9yadwwXeLw6aMeGYn981Bdw

THE JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY Volume 19 SEPTEMBER, 1937 Number 7 -m . M. -\*8 "3 "V8S 1 .V:: the problem of possible systemic effects from ............ CERTAIN CHLORINATED HYDROCARBONS* . Cecil K. Drinker, M.^teleine 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 years it has been known that many of these compounds cause a troublesome acne, and there is a large literature an attack of jaundice about 6 weeks prior io his fatal illness. Late in December, 1936, he became b'.dly 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. Kewas investigations have not been concerned with chloracne but with the possibility of systemic effects following ingestion or inhalation of such products. In the somewhat anemic and his skin, particularly upon the arms, face, chest and back, showed many pustules. Ee died after a brief period in the hospital, and at autopsy was found to spring of 1930, 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. 1 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.-; users, and are lumped together as possib.e causers of acne and even of systemic disease. Since "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. 283 HARTOLDMONOQ21585 i '*^7 *.VT *i. * 284 _ JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY |.S<Pt. tan nit. 19, ruj. 7] EFFECT have a cirrhosis of the liver with acute yel low atrophy superimposed upon it. This man had been exposed to low concentrstions of vapors arising from a mixture of tetra and pentaehlornaphthalenes, together with approximately 10 per cent of a refined chlo rinated diphenyl. While both he and others engaged La the same work bad 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 t. 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 iso lated 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-Sufnt (1934) reports on work done by Touraine and his asso ciates (1934) who examined 60 workers who had been exposed to trichlor- 1. A mixture of tri ; naphthalene. Of these 13 were found naphthalene. to have mild digestive complaints, m- 2. A mixture of tet anorexia, nausea and vertigo, but chlomaphthalen Courtois-Suffit remarks finally, "Ab 3. A mixture of pel sorption is certainly possible and we chlomaphthalen have for proof of it some of the diges In addition, sublimati tive and general complaints which have been due to it. But they appear (3) were collected in o subcutaneously. to be of little consequence considering None of the animal.- t the mildness of the digestive troubles the sublimate from r2 and tiie absence of respiratory phe after 2 months were quit nomena." * - In Touraine's cases the exposure was autopsied. The first ib mals receiving (31 occur: to a trichlornaphthalene, whereas the " day and the last died ot .American cases of acute yellow atrophy Those receiving the sub! were exposed to compounds of higher chlorination. Our own experiments were even more spvc m 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 c eky (1927) reported a number of cases___ elude that "certain chh of chloracne in persons exposed to 'thalenes or impurit 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 ' y- At the beginning ol chlorine content the less the acne.. - Fiinn and Jarvik (1936 Mittelstadt (1935) examined a number fact that there have be of cases of chloracne due to trichlor- .^y of acute yellow atropb, naphthalene and reported a number of (h in men working with chh vague general complaints but nothinf j thalenes but give no de in the nature of serious disease. Rf garding his animal experimentation, ...ug-. to them. These cases at the same as those de? Lehmann (1919) reported that l^-ginning of this paper. mals fed chlorinated naphthalenes re fused to eat after a time and that, whether poisoned by inhalation or by * feeding, at death showed "peculiar* hgf.-q One may summarize j. literature upon system! these substances as folic ^ 1. With the exceptio! lesions in the liver. Flinn and Jarvi .11 tion of acute veliow am (1936) gave, subcutaneous injections enormous doses of chlorinated napb";? ~ and Jarvik (1936) there ^_or even suggestions of . thalenes dissolved in paraffin oil rabbits. The compounds used as follows: gyfcpon human beings. 2. There Is evidence ( that the degree of chior 1 000 It, ", mm HARTOLDMONOQ21586 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 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 m Sal 2S6 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [Sept, mr 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 are not transferred to the food. Skin absorption is the third possible means of entering the body. It may occur but at best must be flight 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 tlmse 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 inhalation experiments were carried out in four iarae air-tight wooden boxes, each capable of holding ten rat cage.-, size _ ,,Fig. I_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 of 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 el^C" trie blower which blew the air through several feet of 7-inch pipe before enter- u Ft tv AY "Jr- *1':. WCb l. 19. no. Z| E iuc the etui of t meter was placed the flow of air in c I'nukl be adjusted from a ealibratin deflector placed at pipe into the box re a uniform < ream of air to th At the opposite out How end--the v.us exhausted thr fitted with a damj a larac central exh About 4 inches the 7-iuch pipe into of the substance^ duced into the inf daily designed p\ 'figure 4), inche diametpr of U inc hold the heated w were made with a that extended to top of the flask wa this fitted a short lenach. This short into a large rubber tightly into a hole ct pipe on the under si< fiask in turn was pi heater made to co below the side arm top- Rubber tubinj !``de arm with a com vir and a gentle str through the melted Motion and assured Into each flask was in ^ntigrade thermom . Pt in place and cou above the 7-in ,'i'bich it passed (figu L approximately 30 . irinated naphtha! HARTOLDMON0021588 rvl. 19, no. t] EFFECTS OF CHLORINATED HYDROCARBONS 2S7 ine 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 cubic feet per minute electric heater. Fresh samples were could be adjusted and read off directly used every other clay, but 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 run 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 stream of air to the two tiers of cages. At the opposite -aid 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). About 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), 7J inches long and with a diameter of If 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 If inches in length. This short tube was inserted into a large rubber stopper that fitted tightly int o a hole cut out of the 7-ineh pipe on the under side (figure 2). The flask in turn was placed in an electric heater made to cover it completely-- helow the side arm and ground glass toP- Rubber tubing connected the side arm with a compressed air reser Fig. 2. Electric heater for maintaining chlorinated compounds at a constant tem voir and a gentle stream of air blown perature in place at inflow end of box. through the melted wax kept it in Motion 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. tnne above the 7-inch pipe through The flask plus the contents was care . *-'.ich 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 Urinated naphthalenes or 20 gm. of weight, used to calculate the average 2SS JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [Sep:. 19S7 amount in a cubic meter of air per flowmeter readings. The figures ob minute as determined by 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 sam pies. Approximately 1 hour was allowed for the wax in the flask.? to melt and come to a constant temperature. At that time the box doors were tightly closed, air bubbled through the flask.?, 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; -- ..mu'itrirOi. f amount of air flowing through the boxes was adjusted and an attempt was made to keep the four boxes as uniform as possible--usually between 165 and 175 c.f.m. - 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 hexa- . chlornaphthaienes. Chlorine --...... content 62.6 per cent. ---------3. A mixture of 90 per cent penta ' and hexachlornaphthalenes plus 10 per cent refined chlorin ated diphenyl. Chlorine cou- ' tent 63.0 per cent. 4. Chlorinated diphenyl. Chlorine content 65.0 per cent. The compounds were selected as rep resenting a certain range in chlorine-' tion and also because of their industrial importance. In each instance SO ^rumats were exposed, 10 rats being placed, Fig. 4. Pvrex glass flask in each cage. They were fed Purin*- pol. 19, no. 7} EFI Dog Chow suppler eggs, milk and cod V* This first group begun on July l. exposure to numb*. `lit chlornaphthaienes ll' 16th. The exposur compounds ceased C ISth, On October ,'v' tive animals were t ' ig- sure from groups 1, - -7-V.77 " xilled after 2 mom 15ih, in order to see Coxbitio.vs Maintain! ornaphtha.lenea p tetrachiornaphthalen and hexachl ornaj 0% penta and hexacl tstkva -lenea plus 10% chlorina ^.^"rinated diphenyl... ;;period would bring ^' .the affected liver * Croup 3 were simih 7exposure on Octob y.f .. ywr examination on , fit The average lengi a.14 hours daily for PS* morning at ab d, and betwee ' p.m. the rats ' i, etc. In or of exposure on a reguis ^HOOOH HARTOLDMON0021590 290 JOURNAL OF INDUSTRUL HYGIENE AND TOXICOLOGY [Sept. 1957 test. The concentrations employed may be regarded as fairly representa tive of industrial experience. Prior to the initiation of inhalation experi ments a number of estimates of chlo rinated hydrocarbons in the air of dif ferent factories were made and the in question is passed over heated plati num in an electrically heated quartz tube and the effluent gas scrubbed in a column of class beads moistened with sodium carbonate containing a trace of sodium sulfite. The beads are then washed down and the chloride deter- SUCTION f Fio. 5. Dimensioned sketch of combustion tube and absorption apparatus. concentrations chosen for inhalation experiments depended on these exami nations. The technic of analysis and the apparatus employed were the work of Frederick R. Millhiser and William F. Hemperly. ; . .. The method and apparatus used for determining concentrations of chlorin ated hydrocarbons in air were adapted from well-known procedures. The air mined nephelometrically as silv*f%r.i chloride. Tebbens (1937) has recently scribed a method and apparatus whidkjgfe-; should be equally satisfactory for work. In figure 5 we show a dime~~~~ sioned sketch of the combustion ` ^ and absorption apparatus as used us in both our laboratory and problems. The absorption tube eol. 19, no. 7) EFFECT somewhat easier to wtu Tebbens's but the esser devices are the same.9 In both cases conver. rinated hydrocarbons acid and subsequent sodium carbonate sbou In our case coneentrat apt to be very low--t less than 1 mgro. per < quently the amount of actually formed in the : so small that it can not either gravimetrically ( 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 I liter conversion of the chi pound to hydrochloric 7 subsequent absorption s f unless the velocity of th * low. Another precautv is that the method is : any chlorinated subs: determined. Furtherm distinguish between soli _ gases but determines the u the results must, of cc puted in terms of total ' At the present time formation as to the am naphthalenes in different plants, and in taatances the measuremt panted several times amounts have beer ^ those used in our exper be remembered n~-i Ti**, '* 1`"tceodmtboufsietioldnsaanmdpali "Ui*on Products, Inc. equipment includes :"on pump with a carryin if* 0001S s&ssSf It HARTOLDMON0021591 nvol. 19, no. EFFECTS OF CHLORINATED H TO ROCARSONS 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 *mall 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-- iny chlorinated substance will be determined. Furthermore it does not distinguish between solid particles and gases 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 chlot*Qatcd naphthalenes in the air of 30 ^fferent plants, and in a number of ^stances the measurements have been ^Pasted several times. Frequently tht amounts have been greater than used in our experiments, but it j*08* be remembered that the rats combustion and absorption appakrr to field sampling is now made uUo-n Products, Inc,, Reading, Pa. ^e'aiwpment includes flowmeter and n pump with 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 mmination 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 trichiornaphthalenes 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 autopsied 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 .'JE, -H: ill - Mi Ii 292 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [Sepi. 19S7 I pot. 19, no. 7] EFF! granular ceUs, 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 hexachlornaph- 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. _,,cells,_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 of 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 whatsoever in other organs. There tients under antisyphilitic treatment. was no acute yellow atrophy^ or any It occurred to us that something d - 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 bsn fgChl 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 peopk normally, being in every respect similar got liver changes such as existed in to the many people who have been rats, changes not recognizable throug11 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 innc over to acute yellow Knowing that oi had liver chances, slight to cause :ecog' we decided to test substances known t 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 foliowi: mals and with the rt following tabulation fioZ* fed 0.75 cc. per . tetrachloride and stomach t. 1. Tnchlornaphlhaler ; ^^naphthalene. Fed 10' I936- 10 rata. No 'J&p'. 2` ?mto and hezachlc &t 8:30 &,m., Nov. 10, : 3 died Nov. 11th _ 10:30 p.m. 1, 1 died Nov. 12th a: 7." 1 died Nov. 12th at 1 died Nov. 13th 11:30 a.m. 3 died Nov. 15th be fe. l4th and 12:3C died Nov. 16th AY.;. iSov- 15th an 3f3th (stiff). ^ l>cr cent penta - percent *1* 1Q:00 a.m., No> & nv 11 00017 mm 7-*^- '.PC HARTOLDMON0021593 vol. 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 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 slight to cause recognizable symptoms, we decided to test their resistance to substances known to cause liver de struction. Carbon tetrachloride and alcohol were selected. Having infor dead). 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 Ralg fed 0.75 cc. per kgm. each of carbon -- tetrachloride and ethyl alcohol by _ . . stomach tube 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 tetra- 3. The penta and hexachlorinated chlornaphthalene. -Fed at 9:00 a.m., Nov. 10, 1936.1 10 ratan. No deaths. 2. Penta and hexachlornaphlhalenes. Fed at 9:30 a.m.r.Nov..10,1936. 10 rats. -"' 3 died Nov. Uth 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 of Nov. ; " -- 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. 8Q p^. cen^ penia and hexachlornaph- a.nd 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 ** at 10:00 a.m., Nov. 10, 1936. 10 rats. we were able to find that was effective. i Bv;v.: 294 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [Sept. 193 In animals with the minor degree of signs of liver injury will be many liver injury which has been described months in returning to normal. we were unable to produce acute yellow atrophy or any variety of liver effect The effect of high concentrations of '.vj` with arsphenamine, cincophen, butyl trichlornaphthalenes with traces of tetrachloride, ethylene chloride and tetra- chlomaphthalene.--The first group of chlorethylene, but carbon tetrachlo- inhalation experiments showed that rh was uniformly effective in dis this material in concentrations averag j-i, closing the existence of liver damage. ing 1.31 mgm. per cu. m. of air was .'fV itj relatively innocuous, judged both by Recovery from liver damage following direct observation and by the carbon removal from exposure.--Animals ex tetrachloride test. This is an in posed to trichlornaphthalenes plus teresting fact since such compounds ttl traces of tetrachlornaphthalene being cause acne, though less potently than wan practically normal on removal from substances of higher chlorination. & exposure need no consideration. In In order to explore the matter further the case of the penta and hexachlor- one of the inhalation boxes was arranged PI I m ------- TABLE 2 Conditions Maintained during Inhalation or High Concentrations or Trichlornaphthalenes plus Tetrachlornaphthalene MATERIAL * ~ Trichlornaphthalenes plus traces of X------------ - tetrachlornaphthalene . .... TEWP. c. 137-200 at. coRcifmunow or AIR IN BOX *" | total IEXPOBCBX J at. dah/t xxpoacxs Tng.l CU. m. 10.97 range High 16.49 Low 5.78 Koure 1232 kourl 16 ms - ^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 only slightly during the third and fourth^ months. When rats in this conditi03^ were giver, carbon tetrachloride alcohol, in some instances their live^.^ showed massive central necrosis rob IS, no. 7| ppj in others this did r rats were used in ti one may conclude cblornaphthalenes t toxic as those of i they are not entire! upon the liver if hii 'T' traiions are inhaled The effects f hig. penta and \cxac: There can he no dm age done the liver b? but in the concent ported no symptom; could be recognize nothing approachii Conditions Mai>NT AIN; Penta and hexachlc atrophy occurred ex Use of the carbon t ' On December 1, 191 subjected to the marked in. table 3. was terminated on Ja % the animals lost wei; v, and deaths began aftt ure. Fifty-five rat; them heavily jaundie tor microscopic exai killed by the carbon t _tod g lived througi S*xpoeure. The liven j kilied for examination degeneration, fe-'^autnanleacsrhosoiws eodf plirvoerrio L-.ttiW - OOOlli fefJi.tSi HARTOLDMON0021595 5,0 ' hi' ` '>:. :f?i '"'" , ,;, -. " ..!-' , - ,- -.- r. v '*' 11 ;*.-/'V1 ^,. ! `' 296 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY \Sepl. 19S7 centrations of these compounds such men never inhale enough of any of as ucre employed cause a certain de these substances to get acute yellow gree of liver damage even if inhaled for atrophy. They may, however, acquire but 8 hours daily. This injury is a substratum of liver damage upon resisted successful!}' by the rats just as which acute yellow atrophy may de was the 16-hour injury but it is none velop. Experience in a number of the less there and destroys the ability plants has shown how easy it is to of the animal to resist the carbon reduce concentrations of these com tetrachloride test. pounds practically to the vanishing point, and every effort should be made Summary of inhalation experiments. to attain such conditions. ii. The findings that have been described briefly will be amplified upon the Gross Feeding Experiments jt'i} pathological side in a further paper by The various compounds used were Dr. G. A. Bennett. What has been ground as finely as possible and mixed HSi given is, however, sufficient to indi- with a standard balanced ration for i ihf' iitii tfflDYii 1i -. . ' -- -- *- m - TU #9 t'M % la S2Kfi 'H . TABLE 4 ` Condition's Maintained during Inhalation or Low Concentrations of Three ' Compounds dubi.vq 8-Houb Instead or 16-Hour Periods '' MA.TXBLAL TXMT. AT.oCrOAtfiCBSNLKTBBAOTXIOW TOTAL at. dartr Expo&trax LXPOaCXB ; --- `` Penta and bexachlornaphthalenea........... c. 149-193 mfj'cu. m. 1.44 90% penta and hexachlomaphthalenea 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 Xourt 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 pi'' an idea as to the possible toxicity of the compounds selected and, if toxicity was observed, some idea as to the site r or sites of damage. _: ' The experiments were successful u> - both respects, and indeed one ro&T-, anticipate that future appraisals of tbe.- possible toxicity' of chlorinated hydro*'; eol. 19, no. 7] EFFEC carbons may often be feeding and do not re rate apparatus and th sary for inhalation exj essential reason for tin :n the identity of the 1 by both methods, and different compounds ,-eem to arrange thorns so far as toxicity is c ever way they are ad: Trichlomaphthalene l-lrachhrnaphthaknc.on May 4, 1936 until Xov?mber2,103t nine 3 gm. of this mix to the food for 10 and this concentration throughout the exper animals were killed i which died on Nov. 2. loss of weight and nc wasting illness of any s death was due to sort spiratory infection wh. tion to the material in Histological exami slight changes in the U of great significance. Tetrg and veniachlm Heeding began on Jur dosage of 0.5 gm. daily -Ml the animals sickene ,'fc'ere either killed or 29 1936. SSL- At autopsy- both gn ^noacally the liver was ' '^"^iected. The liver ce! hypergranulation, - sions and vacuolatii there necrotic cells wen ,*ras & tremendous accu Penta and hezacKloi It ^"ding began Ms; 4 ~ <Wge being used.' E 00030 HARTOLDMONOQ21596 eol. 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 identically worse. so far as toxicity is concerned which 90 per cent prnta and hciachlor- ever way they are administered. naphthalcnes and 10 per cod chlorinated Tricklornaphthalene plus traces of diphenyl.--Feeding began May 4, letrachfonwphthalene,--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 crying 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. F ced 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- Tetrg and veniachlornavhthalenes.-- ^"gan May 4, 1936 on a 3 gm. dosage Feeding began on June 29, 1936. A and tvas 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 veere sacrificed 29, 1936. ^ ^for autopsy purposes on July 8th. At autopsy both grossly and histo- The liver chang-es be. g- an, at once. opcally the liver was the single organ `-There were no changes in otner organs, affected. The liver cells showed swell- A second group of 10 rats was fed a S hypergranulation, hyaline inclu- much smalier dose--0.5 gm. every fiiona and vacuolation. Here and other day. Feeding began May 20, necrotic cells were found. There 1936. The first rat died on May 29th a tremendous accumulation of fat. - Ptnta and hezachhmaphthalenes. feeding began May 4, 1936, a 3 gm. and four more before June 24th. The remaining were sacrificed. Those rats that died showed losses in weight, being used. By June 6, nine while those sacrificed had recovered 29S JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY {Sept. 1337 rot 19, no. effec their initial loss in weight and were gaining, The liver lesions were similar to those found in rats fed penta and hexachlornaphthaienes 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 t was quite innocuous. Tetra and pcntachlornaphthalene showed definite liver damage. Penta and hexachlornaphthalenes 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 - Ndid 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.the total amount a man of 50 . kgL_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 differenc a in the degree of effect but invariably the liver was the sole organ affected and the lesions were those already described many times. Discussion' These experiments leave no doubt as to the possibility of systemic effects from the chlorinated naphthalenes and chlorinated diphenyl. As in the cx-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 trichlomaphthalene 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 and hexachlornaphthaienes but have found no mcrease over normal figures, though the livers, as determined histo logically, were very severely affected. At the present time we are conducting inhalation experiments on a chlonn- ated diphenyl contabbg 55 per cen ...? u of chlorine instead of 64 per cent in the case of the experiments reported in this paper and on a compound a chlorine content between tri *** tetrachlomaphthalene. We are determining the degree to which diet may increase or decrease toxjcitJ?;gb|p this being suggested by similar upon carbon tetrachloride. r. In the basis of these experime15**^ and on many field de different compounds in rooms, it appears saft ^tainly easily attained, ^that the air breathed c ^more than 0.5 mgm. p< IrVt- *"of these compounds ^naphthalene. In the c. compound concentrate are permissible. We many examinations in plants that such ccnc 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 change these opinions g. but today we are com / safe. Impregnating te r arrangements utilizing hydrocarbons are easy safeguard. Compared ^2^ lead tetraethyl and me ?5KL .. CovRTois-Scrri-r: Etude i " professionnelle par ! talene. Ann. de md (1S34). Abstr. of pap A., jlxd Menetrel, professionnelles par 1 *3 derives. Prat, n - 335 (1934). FiJX7'' F. B., AND JARTIE, =5^ wrtain chlorinated naf Uver. Proc. Soc. Exp< , 118 (1936). K. B.: Kurzei Arbeits- und Gewerbet Leipzig, 1919 (p. 2.` ^parin' > #00022 HARTOLDMON0021598 I 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 -tiLha. ti it.h1 e a!ir_ LbreathUedJ does rn\ ot ncoAnnttaniinn ' tri-icnhVillornanpnhVtihtkanllennneft should Vbve 1u1 s-ret fdd , ^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 m. 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 ^safeguard. Compared with benzene, 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 lead tctraethvl and manv other com taining no chlorine. - - ... BIBLIOGRAPHY Couhtois-Scffit: Etude sur Fintoxication professionnelle par le fcrichioronaphtalene. Ann. ce m6d. legale, 14, 122 (1934). Abstr. of paper by Tocraixx, - A., astd MAvetrel, B.: Dermatoses professionnelles par la naphtaline et ws derives. Prat. mfid. Irani;., IS, 235 (1934). Pnnor, F. J3., ajjd Jxbvik, N. E.: Action of certain chlorinated naphthalenes on the liver. Proc. Soc. Exper. Biol. &. Med., 118 (1936)................ ' K. B.: Kurzes Lehrbuch der Arbeits- und Gewerbehvgiene. S. Hir- ,:r; *el, Leipzig, 1919 (p. 251). MittelstXbt, 0.: Gewerbeschadigungen durch Haftax (Trichlornaphthalin). 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). Tovraixe, A., Solexte, Mx-_tbel, B., axd Acbrun: Cinquante-quatre cas de dermatites par trichloronaphtaline. " Bull. Soc. dermat. et syph., 41, 265 (1934). 300 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY (SepL 1SS7 fol, !9, no. 7] EEF Discussion Dr. Cecil K. Drinker: We have had incline them to. First of all I shall ask amart enough to use ecesstully. If this ma adapted for a certain g 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, Dr. fiayers if he will open the discussion for us. Dr. R. R. Savers (Chief, Division of Industrial Hygiene, National Institute of i.-: jii?'. Its.- it. Another materia! vious to this for insula was flammable, cause,, approximately 167 me aay approximately 161 Haskell Laboratory of Industrial Toxicolgy, Wilmington, Delaware): I wish to con gratulate Dr. Drinker and his group on the very interesting and excellent work on the subject. I also wish to congratulate the Huiowax Corporation on the (act 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 Health, U. S. Puhiic 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 manu facturers of the diphenyls. We have been doing some work but not A fkf''gLSVv"- Dever just sure wheth It might have been < ne were quite sure that 16 happened when they with this material. T eiectric cable. It wa. armor on the outside, and was being lowered. proximate!)' 3000 feet to a ateel rope. It sli bottom of tne shaft. \\ 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 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 inspecting it he set it i me cap-lamp. The cs tne fire killed those me mine. Many of course iar with the toxicity and especially with the that we can very well keep in mind. mechanism of the action. Since there is no We are dealing with toxic substances, but Here we have one hi Now we have another < animal which corresponds in all its physio we are dealing with toxic substances each hue to the toxic mati logical characteristics to the human being and every day in industry--harmful sub-., evaluate them. Cental - it is important that such compounds be stances, hazardous substances. That these I am informed, are als studied with different species of animals so can be controlled is well known, no matter that one can get a cross-section of the poten what they are, and that we can use them and not just sure how fiam flammability probably tial dangers. ~ use them in a Bafe manner. Dr. Drinker chlorination increases, In addition, this fact illustrates the im has called your attention to the fact that also increases as voi portance of the pre-employment and peri this apparently has been done and can be odical examination of workers in such work. done in any of the plants w .ere halowax u ereases. according to 1 think that checks with As was pointed out by Dr. Drinker, there used. I have information from one or two _ kave these hazards to ' are individuals who are apparently more of the other mer who are in the audience -q susceptible to certain toxic agents than that in plants wr.ere damage has been none .viy control them. I ieel c we can. others. On the other hand, we have to try --skin damage and apparently liver damage .uu-. Ferhaps we can find o' to detect the'very first signs of incipient to some of the workers--the manufacturers yy better even than th: poisoning in order to prevent more serious have since corrected the conditions and &p- ygr damage. In the present instance it is very parentlv have adequate engineering coo- ^ Present time I am advu better. I am advised t; difficult to find these very first symptoms trol supplemented with adequate medic" auomarines, it is quite 1 because there are no adequate methods, but I trust that in time the scientific profession will supply the medical profession with control .. , ,, u i-i*-':: *6-fia mm~~a--bl*ee flUDstanc After all, the proof of the pudding -ffi-* `fcetr electrical wire the eating. If the man does not get the di**-)*- '. adequate methods which will allow the ease your engineering control is succ physician to determine incipient damage of If he1 adoes get tnhe disease, no matter -- - a. Cecil K. Drinks -you care to say a word? the organ before serious clinical symptoms become manifest. Thank you. Afternoon Seesion Dr. Cecil K. Drenker: In this discus sion I will cal! on one or two individuals and you have done in the way 0/ youh...a..v..e..n. 't bee__n s_ u_ cc_e__s_s_fu__l. We must I* hand b hand. Neither profession can be successful. We have got to together whether we like it or not. T pen to like it. There is one other thing. ___ . Da. Albzs " upational Diseas **icut Department o: t Cux.): Dr, Drinker, I < fi aj'thing that I cam say ( material in Cormec: I shall expect others to speak as their notes rials are concerned I thbk we ougDt w 00024 HARTOLDMON0021600 vol. 19, no. 7) EFFECTS OF CHLORINATED HYDROCARBON'S 301 smart enough to use every one of them suc number of so-called cases. All I can say is cessfully. If this material is particularly & confession of ignorance on our part at that adapted for a certain purpose we should use time and I was very glad to see that your it. Another material that was used pre digging into the literature as thoroughly as I vious to this for insulation purposes, which you have hasn't elicited any further infor was flammable, caused a disaster in which mation than we were able to g"t, basically. approximately 167 men lost their lives. I About all we could find was i mut the two t say approximately 167 because they were cats that- our friend, Lehmann, experi never just sure whether it was 167 or 168. mented with. We got in touch with him and It might have been one or two more but they he confessed that the amount that he had were quite sure that 167 lost their lives. It given the cats and his method of determin happened when they had insulated a cable ing it were probably subject to very serious with this material. They had an armored scientific criticism, and we agreed with him electric cable. It was covered with lead on that point. * armor on the outside. It was 1200 feet long We felt, and I am very glad that it is what and was being lowered into a mine shaft ap you feel aa a result of your experiments, proximately 3000 feet deep. It was lashed that if we put in an efficient ventilation sys to a steel rope. It slipped and fell to the tem sufficient to prevent the dermatitis, we bottom of the shaft. When the foreman was probably wouldn't have liver carnage. inspecting it he set it on fire with his car That is what we did entirely empirically. bide cap-lamp. The carbon monoxide from I think that is about all I have to say. I the fire killed those men that were in that have been delighted to be here and to have mine. Many of course escaped. as many members of my staff here aa I could Here we have one hazard, a fire hazard. jack out of the office. We have been de- Now we have another one, a health hazard lignted to listen to the discussion. due to the toxic materials. We have to evaluate them. Certain of these materials, Dr. Cecil K. Drinker: May we now I am informed, are also flammable. I am make the discussion general and those who not just sure how flammable they are but have questions please volunteer. flammability probably decreases as your chlorination increases. But your toxicity Mb. Manfred Bowditch (Director, also increases as your chlorination in Division of Occupational Hygiene, Massa creases, according to Dr. Drinker, and I chusetts Department of Labor and Indus think that checks with other findings. We tries, Boston, Mass.): I would like to second have these hazards to balance but we can very strongly what Dr. Sayers has said with control them. I feel quite confident that regard to the approach to this problem in we can. proper control rather than by prohibition, Perhaps we can find other substances that which seems to me wholly unnecessary not lre better even than this material. At the only in this case but in the case of other present time I am advised that we have no toxic substances with which we have to deal. better. I am advised that in ships, Buch as The problem of proper ventilation seems to submarines, it is quite important to have a me relatively simple from what I have heard ^^-fi^mmable substance for the insulation of the situation thus far. The problem of of their electrical wire. maintaining that ventilation properiv does not seem to me quite so simple. I think it Hu. Cecil K. Dbinkeb: Dr. Gray, would is going to be quite necessary that there Jon care to say a word? should be a very adequate inspection of the plants using ths materials and I can Albert S. Gray (Director, Bureau assure you that that will be the case here in ` Occupational Diseases, State of Con- Massachusetts. ^eficut Department of Health, Hartford, When this trouble first broke in this state Dr. Drinker, I don't think there is a little over a year ago we issued a quite worthing that I can say except that we used strongly worded warning letter to all plans material in Connecticut and we had a using these substances and it has all along '.'-n laitif `.'rtV-.v . HARTOLDMON0021601 302 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY (Sept. 1937 been my plan to follow that up with a fur ther letter bringing the aituation 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. Sarm ford Brown (President, Ealo wax Corporation, New York, N. 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, particular!} :'ie 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. Now 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 itBasically, however, if the variation in the chlorinated naphthah ne 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 alee advise our customers. Virtually every cD` sumer of these materials at some time another has been given their technical of chemical designation along with their van* ous properties, whether they be physical of chemical. ' Those are some of the practical problem* pol. 19, no. 7J with which all i t. synthetic organ mer.t is so rapid can t even keep i menu sometime; 1 doing. Hu M. F. R. K -Vy age.-, York Wire* -st;; ^ ork, Fa.): I an jvjl 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 aH 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 *as 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 rhe time of his' ei Plained of this coni ndvised that he see vapidly developed ^ the hospital anc <Ued. More serious tha: -Vase?>/* "*t we had 50 othe as far M the a< rV tion that , ``ad was to throw j ST; The? ^ . ` for treating wi but not so easi ^ have thrown and 2jd, "7 HARTOLDMON0021602 ro/. 19, no. 7] EFFECTS OF CHLORINATED HYDROCARBONS with which all manufacturers of chemicals there was no substitute and there is none are confronted today, particularly in the today in spite of all the efforts we have made synthetic organic field where the develop through our own research laboratories to ment is so rapid that our 3aies departments can't even keep up with the research depart ments sometimes, in knowing what they are find one. But we did develop--and I v as most closely associated with it--and ot up a m doing. routine for bringing these men back to nor mal health conditions. A number of them Me. F. R. K.viuer ^Assistant to Man were sent to Dr. John H. Stokes and to Dr. ager, York Wireworks, General Electric Co., 0. H. Perry Pepper of the University of York, Pa.): I am certainly pleaded to have Pennsylvania Hospital, and the others to this opportunity to say a few words with Dr. Isaac R. Pels at Johns Hopkins. reference to the "xperience we have had at Through their recommendations and studies our York plant. I perhaps should say that we employed a trained nurse and two local again in this case experience alone has been physicians and you might say established a the best teacher. I have lived with the small hospital and its facilities at the plant. problem at York with the men who went Through the application of quartz light, through the experience from its beginning. x-ray, mechanical removal of comedones It is only lj years ago that we had in the and the treatment of pustules that de neighborhood of 50 to 00 men afflicted with veloped in later stages, an utterly strict various degrees of this acne about which you routine where the worst cases were adminis all know. Eight or ten of them were very tered to each day for a period of 15 to 20 aeverely afflicted--horrible specimens as far minutes, another group who were less seri- as their skin condition was concerned. One ous three times a week, and still another man c led and the diagnosis may have attrib group once a week, we have in this year and uted nis death to exposure to halowax a half brought each and every man back to vapors but we are not sure of that. There a normal skin condition. Those who were 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 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 s' ill ' iSl tion that he had. he appeared to me very are using today is even greater in quantity thin, psdlid in his appearance, and I would . and id types than we were using a year and not Bay from my poor knowledge of the a half ago. . physical make-up of the human being that With the adequate ventilation system we he presented a healthy appearance. How have installed, with the routine for change ever, it was only for a 6 months' period from of clothing from street clothing to work the time of his employment that he com clothing when they come to work and the plained of this constipated condition and we reverse of that process, with the assurance advised that he see his home physician. It that a Bhower will be taken before the street tapidly developed to the point where he was clothing is again put on, we have found no 111 the hospital and in a very short time he recurrence of this skin trouble. Each and died. every man working with halowax products, _ ^dore Berious than that perhaps is the fact either from solution, from solid compounds we had 50 other men in very bad condi- or handling the wire insulated and treated "n as far as the acne was concerned. The with it, is examined twice yearly with a com reaction that several of our executives plete physical examination, including blood ^d was to throw it out--get it out of our analysis and efforts to determine any liver They didn't want anything like asmage. , ^or treating wire. But that was easily However, there is the point which was . OX but not so easily done. We might just . very definitely brought out this morning. ** weU have thrown ou_ business to the four We do not know as yet when this thing jetni *dnda and said, "We'll close up," because starts. I believe it would be cf great help ha?*1 0Q02Wfff HARTOLDMON0021603 304 JOURNAL OF INDUSTRIAL KYGTENE AND TOXICOLOGY (Sept. 1937 to ua all in Industry if some 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-inls, 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. Kaimeb: 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 hip1' 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 iS 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. Af.thtr 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 work ing 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 se-.n 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 o: intoxication from this substance, the skin offers an easy way of proving whether your method of ventilation is efficient or not. If there ar any cases of acne or of this dermatitis occur- . ring in a plant where halowax or the chlorin ated naphthalene or chlorinated diphenyl4 . are used, then that shows that there is \ ficient concentration of these substances t : the air to cause plugging of the follicles **"-4 to cause a skin condition. If there is sU* ~ cient concentration to do that there M rol. IS, no. 7] sufficient concentration t poisoning in the few peopi sensitive to the action of 3t1. bons. Everybody is not them. If they were, of people who have been ha\ stances, more would hav< & disease and it would ha\ very much earlier. This r in Germany as early as 19 While I cannot add methods outlined here ior of ventilation and so fori if you go into a plant ar any acne present among this material you will kn sufficient of the substance : acne and consequently sufi be dangerous to the few 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 endeavi confine our analyses to or ratus, so that at least our comparable as we can maki 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 ttL8s, State of Connecticu Health, Hartford, Conn.) tfctuation of the halowax 'vouidn't be preferable to discuss the method t throughout the country' fu tion of chlorinated naphtt Ur. Cecil K. Drinker 84 tent is concerned it is b discussions with Mr. Hi afterward. But determining some uniform) 8 ^hile a . least is, I thina. feri interest to us. 00023 vol. 19, rw. 7] EFFECTS OF CHLORINATED HYDROCARBONS 305 sufficient concentration to cause systemic poisoning in the few people who are hyper sensitive to the action of these hydrocar bons. Everybody is 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 ,\nd so forth, I can say that if you go into a plant and find that there is * any acne present among the workers with this material you will know that there is sufficient of the substance in the air to cause acne 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 an 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 deterrnination of the halowax I wonder if it wouldn't be preierable to have Mr. Hem- discuss tne method he has been using nroughout the country 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. Hemperiy and Dr. . r*udt afterward. But the question of t,eterminng some uniformity of technic for & whiie 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 material in air, length of sampling, type of apparatus, and so forth. It has been suggested that we endeavor to agree upon some uniform procedure for that and as figures begin to come in. as they w\i 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 anaivses 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 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [Sept. 19S7 at work with 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 beiieve 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 so that Ln 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 source 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 have 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 nf service to the American Public Health Asso ciation Committee if a sub-committee from this meeting, collected perhaps by mv brother and those of you involvedVith 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 irom 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. X. Setterlind.J Mr. Hervet B. Elkins (Chemist, Divi sion of Occupational Hygiene. Massachu setts State Department of Labor and Indus tries, Boston, Mass.): In connection witn what Dr. Schwartz ha3 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 cblo* rinated naphthalenes. It is also my under standing that these are more likely to cause a severe skin irrication than the straight chlorinated naphthalenes. On the otner rol. 19, no. hand, from Dr. Drinke pidge that the straigh' thaiene was nearly as mixture of it with a sn. I rinated diphenyl. In the condenser fac our cases there is no cl used and no acne of th< the reports on the insui Dr. R. Emmett Kell ical Co.. St. Louis. Mo.) anything to ti,- inbor.'.to has b*-en quite a little h tion in the last several . our plants wherp we hav ine this chlorinated dipt ou bservation that alt! si' : we did have a nior ferns of skin eruptions w atm to attribute as to ca hr.r.-jritv in the benzene the chlorinated diphenyl, any systemic reactions Re have examined them from what laboratorv ntight help us and from Point. Aiso from chioi alone there have been nc poisoning reported. I don't believe that we laboratory results into tfc without paying consider volatility of difierer.ts *ay they are being used. E*e. John A. Hooret jsatologist, Kalowax Corp Ech.): I have had consid vfith the dermatological a cm. The exDerience at t at Wyandotte definitely w 115w did increase when u,-^d rather than the str 6tphthalenes. From the discussion rp think the observation L at the chances are tha Problems will disappear air b Probably true. Howev t^rtain precautions, certab ^.e*1 J'r micht say, she 't'S men who are gon 646 Products, even then 00030 -- HARTOLDMON0021606 vol. 15, no. rj 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 me of the type described in the reports on the insulated wire factories. Dr. R. Emmett Kellt fMonsanto Chem ical Co., St. Louis, Mo.): I can't contribute anything 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. Eooket (Consulting Der matologist, Halowax Corporation, Detroit, Mich.): I have had considerable experience with the dermatological angle of this prob lem. The experience at the Halowax plant at Wyandotte definitely was that the derma tosis did increase when compounds were t^d rather than the strsigat chlorinated Daphthalenes. From the discussion we have heard today 1 think the observation Dr. Drinker made *Fat the chances are that dermatological Ptoblems will disappear along with the other ** Probably true. However, I think that Attain precautions, certain insurance meastlre*i you might say, should be taken in kir men who are going to work with th products, even though we are going to ai'rmpt 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 deveicr-'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 rarefuiiv for a history of previous liver diseases. '. here are other thLngs 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 stated 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 your 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 thatdueto 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 or 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 {Sep!. 10.17 that they developed acn< more often and more severely after they started making compounds. It may he 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 are con cerned. such as various plasticizing agents? How much do we know about those insofar tas development of acne is concerned? Some of these compounds have a half dozen con stituents in them other than chlorodiphenvl and chloronaphthalene. We are at the present time considering the chloronaph thalene 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 jus: 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 anj- 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 mu.-h more than the --laer people in whom the sebaceous gianus 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 halowax or chlorin ated naphthalenes or diplu nyls but can occur with any condition that blocks up the sebaceous follicles of the skin. Dr. Rotal Meeker (Special- 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 wanted to drop that as a hint for this committee to consider in its work. In spite of wirat 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, tne 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 determine that because it seems to me. from the shght knowledge that I have of the industrial application of halows:. 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 anythin? about those Massachusetts cases of very severe dermatitis and I am not so sure but what there was some question of liver dam age there. Nobody has said anything about them at all. There is no question tne 4- Yi:. 1 i'"/. 10, no. EFFE that the condition, v-l.a tions might have beer.. < cold wire, in a cvitffiu 1 think this needs a grt Dr. Drinker, than you : have hven able to give i curiou1 about is the wa\ the protective labor law? both the employer and tl l listened with very g expositions of suggested cation of nalowax. elder and diphenyl. It seemt left very much to be ae why the application of pound, if it is necessary to use this rather dangero be 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 froi all contamination from ft rated haiowax 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 (\ General Manager, Ro-.i Corporation, New Have:, very glad to tell of ou-- e: help the picture along. C oeen more or less parallel in as much as we manufac: wire. We have avoide ture that he ran into, prt f&ct that shortly after 19 Lenzene as a solvent ior a; Nt got into anemia dir. fumes and had to i vem. dating system to r fumes from the machines compounds to the wire installation of that equipr 10 get a substitute for ben ut of the picture. are still in the sami is as far as finding a su ^ax. There is none that ? `vquentiy when we went t- HARTOLDMON0021608 * v. . (* * mri4 v&> I^XO jv 2** -- r ^ J -**iy <- V-^i; &'&*>'' s t-ul. IS, 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 adaptable 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 cumpoum. In order have been able to give it os 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 hu. wax, chionr.3ted aaphthaiene changed to the halowax compounds we fol and diphenyi. 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 l to use this rather dangerous substance, can't wire to come out. There is enough exhaust be done in a practically closed pot. If you suction on the enclosure to prevent any i 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 how they have handled periodically it is necessary to open the pot I 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: Mhat is the veloc ratus, and it seems to be entirely adequate. ity when the door is open? Mf.. 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 beip the picture along. Our experience has been mere or less parallel with Mr. 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 -.hat shortly after 1923 we were using benzene as a solvent for asphaltic materials. Me got into anemia difficulties with ben zene fumes and had tt .ustall a compieie ventilating system to remove all those fumes from the machines that applied the compounds to the wire. Following the u^stallation of that equipment we were able get a substitute for benzene, so we got it out of the picture. Me are still in the same fix as every one efee is as far as finding a substitute for halowax. There is none that we know of. Con sequently 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 cvwn the air flow and reduce the V'-ntilation efficiency. Da. Royal 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. '*fr 7 V5h41 rjoSi -.- Vi wm II# l A V." _ -.-.I&f-S!;.. K-rT.V>S'.-<r.,v: - .> Lfr: '.j-j;Ai'-'jili/iT i t&W i.- fycvl&ipipll i S'j 00033;l;yEs, mmm HARTOLDMON0021609 ;-;io JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [Scpi. 19S7 cot. 19, no. EFEEC Dr. Cecil K. Drinker: Yes. It ie detectable readily through the outflow pipe. Mr. B. H. Reeves: Those in the far end probably didn't get the concentration. Dr. Cecil K. Drinker: \Ye 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. complaints were bona Sde. had no dif ficulty in handling cold wire and the men had no skin trouble. Yet when they did the same thing with possibly the application of heat in tunnels, ships and s: Urth, they actually did develop trouble. We have used, of course, the icterus index in following some carbon tetrachloride cases and I wondered what you have to say about that. Is that o: no value at all in the case of liver damage in this material? Dr. B. L. Vosbcrgr: questions in mind. I w wnat Mr. Brown w.mui ? hihty of using only eh: .rinated naphthalene fA Mr. Sand ford Bro simplify our problem exn from the commercial sta (he toxicity standpoint. 1 think that Mr. Kaime: Dr. Emery R. Hayhcust (Consultant Dr. Cecil K. Drinker: I don't think so .in Industrial Hygiene. State Department of un:il it gets so extreme that we know it any Health, Columbus, Ohio): I would like to way. ask if it wouldn't be possible to put a cold water line around that trap and deposit it Dr. B. L Vosbcrgh: I did write down a all before the air escapes from the trap. few questions that came to mind. Some of them have been answered and some are Mr. B. H. Reeves: We have tried cool foolish but I shall ask the:: anyhow. ing the surface of the exhaust pipes in order It occurred to me that trichlornaph- 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 of the ventilating .-"stem. While we have largely for the Halowax Corporation to use found t slight advantage in doing so it only that one material adopted with other hasn't at all paid for the expense. It is known chlorinated compounds to meet the much easier to take the piping down. Con requirements of customers? That is one sequently I doubt the possibility of remov of the foolish ones probably, but I shall ing it all by cooling the surfaces of the trap. just ask it. 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 then you would have the problem of remov pretty well damaged. I talked to you and ing it from th- coils after you had collected you said you hadn't worked that out with it and it would involve rattier complicated the animals as yet. procedure. Dr. Cecil K. Drinker: In that case we Dr. B. L. Vosbtrgh (Medical Director, set aside a certain number of animals to General Electric Company, Schenectady, recover, after knowing that a certain New Y'ork): We have heard about the pos amount of damage had been done. Then sibility of preventing liver damage and skin we started to kill them but we invariably rr. trouble among manufacturers of wires and ran out of rats before they ran out of lesions. cabies and so forth, but like the old rhyme, We don't know how long it lasts. to object because he wo-.': the technical eflects he dc The same thine applies ' industry where we are u chlorinated products, The problem as we ,-ee which we intend to study our program for this com will be done under the Drinker brothers), is to t: demarcation and whether complicated chemical s: Borne one thing that cause we could take bexachicr remove I per cent of some uent with which we are and eliminate the toxic.t a lovely solution. Wbeth able to attain that I dor.' one of the things we have As I said before, that is with which all manulactu thetic organic products s some stage, either in their commercial developments question of timing as to wi the work, how much yot whether you know how to t learn that first. every dog has fieas and the fieas have fieas, Dr.. Cecil K. Drinks:: we aiso have customers who use wires and De. B. L. Vosbergh: Have you given some other important mat' cables in tunnels, in enclosed spaces, splic them calcium and glucose as you would with tne meeting adjourned. ing them together and doing all sorts of carbon tetrachloride? things. I am not at all certain that we know what ae concentration of these chlorinated Dr. Cecil K. Drinker: Not yet, but we hydrocarbons i3 under those conditions. are doing an experiment now with one group I About the time we were having so much on a very high calcium diet and another trouble at our York factory some of our group on a calcium free diet. The whole E>b. r. r. Saters: M: more with regard to what E 00 syphilis? If you are g your workers who ha customers began complaining. We thought question of calcium in the diet, of giving w? were having a hysteria of halowax mania milk daily to these people may be worth throughout the country. Some of their while. IV 0003d HARTOLDMON0021610 vol. 19. TU r] EFFECTS OF CHLORINATED HYDROCARBONS Dr. B. L. Vosbcroh: I just had those syphilis during the time they are working arSS questions in mind. 1 would like to hear for you, you are probably going to lose some what .Mr. Br wn w'uid <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 Wes chlorinated napht:. ne. consideration to seeing that conditions are proper and suitable for them to continue lr-l 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 I think that Mr. Kaimer won! be the first syphilis. We have not found that to be to object because he wouldn't be able to get true in other places and I question whether the technical effects he desires in the cable. The san. thine applies throughout all the industry where we are using these higher this is one of the places. I may De in error. % 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 a' 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;, is 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, e 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 ae uent with which we are not now familiar comprehensive program in new to carry on. ill and eliminate the toxicity, that would be Therefore we want to continue that same ; * * ** j1" a lovely solution. Whether we will eve; be type of cooperation. DO en able to attain that I don't know. That is one of the things we have in mind. There is one thing that I want to bring up in that connection, which will have to be V- ' 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 gas thetic organic products, are confronted at the necessity of not- creating mob hysteria KY'5** some stage, either in their laboratories or in on the part o: 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 iin the work, how much you should do, and ing situations in the various examinations en whether you know how to do it. You have he has made. I know that he would be glad Jy to learn that first. ' to relate them and give the benefit of hiB .is. experience to the heads of any of these state :;.rr>jrrs5sc. i departments who will have the direction of Dr. Cecil K. Drixeer: L'nies.- there is this work. Otherwise I can see where we en ith *Ee other important matter I will declare tOe : meeting adjourned. will be unable to get the full cooperation of not only the individual workmen but the piant foremen and the management, and we *1 i 't'VrW' l-l'mg?" 7 | i Da. R. R. Sayers: May I say a word must have that if we are to get the results i- i Ioffes we ore with regard to what Dr. Hookey stated that we are shooting for over the next sev up n syphilis? If you are going to eliminate eral months or years. This thing may con cISSner au your workers who happen to develop tinue, probably will continue for years. ole :ag rth oooM:fI 2"e.'"'>!. -ynr, {I jsr v- -***!' HARTOLDMON0021611