Document 8VG2DM0jrGqNYeRq99Lr268X5

SYMPOSIUM ON CERTAIN CHLORINATED HYDROCARBONS Harvard School or Public Health, Boston, Mass. June 30, 1937 Program 1. The problem of possible systemic ejects from certain chlorinated hydro carbons. Crcn. K. Dajsxra, Uadclertc Fitlo WraaES aj Gsaocvilix A. Bejcxt.ti Dfptrmmt 4 PhyriJ.;;. R*rttri ititni / P*-!i' Btilti jad Dafanmt<d <f PaJkataty, Btn*d Urdial ScM, V ia. 2. Demonstration of laboratory method' for ventilating, pnations emsloving chlorinated hydrocarbons A rtiscusssioc of permissible concentrations of such compounds in the air. Aulmt C. P. Vxclov, M.M.E. dim. flarwtf S'imhf C.'.V Baaltt A VO Pbiui* Dunkc*. Ch.E. Pnfmar *4 /afatfu.* By:Um, E --vaaJ ./ Bt ilia *3'. A description of the lesions found in the liver of animals subjected to various cfaorinated hydrocarbons. GiA.vvau: A. Bcv.sttt, M.D. tiM uli m Ptii'iaiJ. Bant'd It'liezl StW (The aacond and third (wpen will appear dtswhcic. Copies of them will be sant to all who attended the tympesuznj BBRNOO1933 TOWOLDMONOOQ1498 j j : : \ -j ' | f * I ( . : j I ! ! . ' \ i I SYMPOSIUM ON CERTAIN CHLORINATED HYDROCARBONS Harvard School of Public Health, Bostoh, Mass. June 30, 1937 Program 1. The problem of possible systemic effects from certain chlorinated hydro | carbons. Cecil K. Dukxex, Madeleine Field Waeees and Geanvzux A. Bennett Dafortmomt of PhytioUfy, fftrwrf School of PwUU Smith nrf Dtfmrtmod of Pothalofy, Banod Hailed Sddd, Bo**, Hsu. 2. Demonstration of laboratory methods for ventilating operations employing chlorinated hydrocarbons. A discusasion of permissible concentrations of such compounds in the air. C. P. Yaolou, MATE. A jjvJcaf fnfujm /Wnj*iaJ Dytwmt, Rim'd Stkmt tf Puiik Bmltk aim Pirlif Diin-ees, Ch.E. ' rnjmm 4 Imdmbitl Bjfitm, Bwrtti t( rMt Bml* 3. A description of the lesions found in the liver of animats subjected to .various chorinated hydrocarbons. Gsakvius A. Bissrt, UJD. tamStkimrt*&a, Btnt* tltiial Sci-i 1 i t S- (Ths second and third papers will appear ebewhem. Copies af them will be sent to all who attended the symposium ) ,. . - GBRN001934 TOWOLDMONOOQ1499 THE PROBLEM OF POSSIBLE SYSTEMIC EFFECTS FROM CERTAIN CHLORINATED HYDROCARBONS* Cecil K. Drinker, Madeleine Field Warben and Granville A. Bennett Department of Pbyriolojy, Harvard School of Public Health and Deportment of Pathology, Harvard litdical School, Botton, Moot. HE use of ehlorinsted naphtha rapidly and thoroughly as possible.t Tlenes and compounds of allied pharmacological possibilities is In brief these cases were as follows: Patient 1. Male, age 21. The previous extremely aide, and with the stemadeydical history of this man was in no way growth of the use of electricity is cer significant except for the fact that be had tain to expand much farther. For yeftrs 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 to his fatal illness. Late in December. 1930, he became badly constipated and had much abdominal pain and distention. When ad mitted to the hospital he was slightly jaun upon this phase of the subject. Our diced and was evidently very ill. Be was 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 theanss, face, chest and back, showed many pustules. He died after a brief period in the hospital, and at autopsy was found to spring of 1936, the Halowax Corpora tion, a division of the Bakelite Cor poration, called our attention to three fatal eases of jaundice in workmen using chlorinated naphthalenes and chlorinated diphenyl, and requested that the subject be investigated as Baeaived far publication June K, 1W7. t The Halowax Company makes many products besides ehlorinsted naphthalenes, and it has come to our knowledge that all of these products are indiscriminately called "halowaxes" by purchasers and users, and are lumped together as possible causers of acne and even of systemic disease. Sines "halowax" is merely a trade designation, ears should be taken to describe compounds by their ehemical names and then avoid condemnations which are both troublesome and misleading. 6BRNQ01935 TOWOLDMONOOOI500 284 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY ISept. itST i have a cirrhosis of ths livsr with scats yel who had been exposed to trichlorlow atrophy snpcrimpo--d upon it. This naphthalene. Of these 13 were found msa hsd been exposed to low concentrations of vapor* anting from s mixture of tetra to have mild digestive complaints, and pentaehlornaphthslenee, together with anorexia, nausea and vertigo, but 4 approximately 10 per cent of a refined chlo Courtois-Suffit remarks finally, "Ab rinated diphenyl. While both be and others sorption is certainly posable and we engaged in the tame work had chloracne, there were no other disturbances of health have for proof of it some of the diges in fellow workmen, nor waa there any pre tive and general complaints which cipitating cause for the acute yellow atro have been due to it. But they appear phy such as treatment with arspbenamine or exposure to dangerous concentrations of carbon tetrachloride. Patient t. Tbit waa a young man who died in February, 193S, after an acute illness characterised by jaundice. He had been to be of little consequence considering the mildness of the digestive troubles and the absence of respiratory phe nomena." In Touraine's cases the exposure was exposed to fumes arising from a mixture of penta. and bexachlornaphthalenes. 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. to a trichlomaphthalcne, whereas the American cases of acute yellow atrophy were exposed to compounds of higher chlorination. Our own experiments indicate that trichlomaphthalcnes re Patients. Another young man employed with Patient 3. He became jaundiced in Mareh, 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 quire enormous dosage, far beyond anything encountered in industry, in order to produce liver damage. Teleky (1927) reported a number of cases of .chloracne in persons exposed to tained as to a precipitating cause, and there was no record of preceding attacks of jaundice. chlorinated naphthalenes with a chlo rine content ranging from 14 to 53 per cent. He found that the lower the In addition to these three very re chlorine content the less the acne. cent fatalities, we have learned of four Mittelstfidt (1935) examined a number other possible cases, none of them of cases of chloracne due to trichlor- fatal. All of these have had jaundice naphthalene and reported a number of and the entire group consists of iso vague general complaints but nothing lated individuals who have been icked in the nature of serious disease. Re out of large groups having the same garding his animal experimentation, exposure. In but one instance. Pa Lehmann (1919) reported that ani tient 1, is there record of antecedent mals fed chlorinated naphthalenes re disturbance of health, and the general fused to eat after a time and that, health of fellow workers has been good. whether poisoned by inhalation or by Such cases have not been reported feeding, at death showed "peculiar" in the medical literature and only occa tenons in the liver. Flinn and Jarvik sionally can one find reference to sys (1936) gave subcutaneous injections of temic effects of any sort. For exam enormous doses of chlorinated naph ple, Couitois-Suffit (1934) reports on thalenes dissolved in paraffin oil to work done by Touraine and his asso rabbits. The compounds used were ciates (1934) who examined 60 workers as follows: 6BRN001936 V WW. WIJ! S' TOWOLDMONOOOI501 i i |S&.IHT . trichlorvcre found mplaints, :igo, but .lly, "Abi' and we the digesrs which ry appear unsidering troubles ;ory phe- isure was uercas the r atrophy of hitter pcriments .denes rer beyond :ustry, in .go. Telr of cases -nosed to h a chlo- w 53 per ower the he acne. - number uichlor;anber erf . nothing Re^tation, :hat aniienes re ad that, m or by peculiar" d Jarvik etiona of J napha oil to -ed were rot. It, bo. 7} EFFECTS OF CHLORINATED HYDROCARBONS 285 1. A mixture of tri and tetrachlornapbthalene. 2. A mixture of tetra and penta chlomaphthalene. 3. A mixture of penta and hexachlomaphthalene. In addition, sublimates from (2) and (3) were collected in oil and injected subcutaneously. None of the animals receiving (1) or the sublimate from (2) died, and even after 2 months were quite normal when autopsied. The first death in the ani mals receiving (3) occurred on the 12th day and the last died on the 26th day. Those receiving the sublimate from (3) were even more severely affected. Autopsy in these animals revealed striking changes in the liver, not, as described, entirely characteristic of acute yellow atrophy but sufficiently suggestive to cause the authors to con clude that "certain chlorinated naph thalenes or impurities contained in them are capable of producing yellow atrophy of the liver in the rabbit." At the beginning of their paper, Flintt- and Jarvik (1936) mention the fact that there have been three cases of acute yellow atrophy of the liver in men working with chlorinated naph thalenes but give no details in regard to them. These cases are undoubtedly the same as those described in the beginning of this paper. Cne may summarise the meagre literature upon systemic effects from these substances as follow*: 1. With the exception of the men tion of scute yellow atrophy by FIinn and Jarvik (1936) there are no reports or even suggestions of serious effects upon human beings. 2. There is evidence (Teleky, 1927) that the degree of chlorination is sig nificant in relation to the production of acne. In the work of Flinn and Jarvik (1936) the compounds produc ing serious liver injury were the most highly chlorinated of those tested, though the chlorine contents as given by analysis vary surprisingly little. 3. There are no published figures upon the amounts of various chlorin ated naphthalenes in the air which witl produce injury of any sort, and while the work of Lehmann (1919) and of Flinn and Jarvik (1936) point to the liver as a possible site of injury this indication rests ujn such extreme dosage as to fail to apply directly to human exposure. Experimental Work In apprabing the possible toxicity of any substance met in indust ry it is first necessary to determine the prin cipal route of absorption. In the case of the compounds under consideration there can lie no doubt that inhalation is their chief means of entering the body. They are used hot in a great variety of operations and volatilize in varied degree. They are often applied in solution in such volatile solvents as carbon tetrachloride and toluene. The amounts reaching the air under such circumstances are hardly detectable. It will however be shown that carbon tetrachloride adds to the toxicity of the chlorinated naphthalenes and allied compounds, and if there is possibility of inhaling these compounds in other parts of the factory then inhalation of carbon tetrachloride adds a decided hazard. Under such circumstances solvents such as toluene should be used. Observation in a number of plants causes us to fed that even though -- -,m "**- 1 ii'stwt*;--.wipw. a "*~rn GBRN001937 TOWOLDMONOOOI502 -- --L^iHnfi~ii aam i i -Ii i i i i i a ir t ~ n ^ i"T ` f"rrf m ------' JL. <> it a.--a,-, j Chi 286 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [ScpC UST 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 slight when compared to the steady inhalation of finely divided or gaseous material in the air. tion. They thrive upon a diet very similar to man, and in the case of these 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 large air-tight wooden boxes, each capable of holding ten rat cages, sire 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 Experiment* Animate.--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 waa equipped with an individual variable-speed deotric blower which blew the air through several feet of 7-inch pipe before enter rol. li ing t mete' thefi could from deflw pipe sure strcai At outdo was t fitted a larg Alx the 7of thduccd ciallv (fipin dianie hold t were r that t top of this fi Icnstli into a tightly pipe oi flask ii heater below top. I side ar voir an througl motion Into cii centigr. kept in time al which i Appr chlorine tjw .mu.Min-j in BBRNOO1930 Li.I .mjrn* TOWOLDMONOOOI503 tST i very these .,-<ible iiifiint. -.-ristics .1 make both .ilation ;n four each siie \ i \ n. t five -it was ;x.`tied place -W box luccd meter :>!*pcd ' clccMmgh nter- rot. 1$, no. 71 EFFECTS OF CHLORINATED HYDROCARBONS 287 ing the end of the box. An orifice meter was placed in the pipe line, and the flow of air in cubic feet per minute could be adjusted and read off directly from a calibration curve. A vane deflector placed at the entrance of the pipe into the box was adjusted to as sure a uniform distribution of the stream of air to the two tiers of cages. At the opposite end of the box--the outflow end--the air from each box was exhausted through a 7-inch pipe fitted with a damper and connected to a large central exhaust fan (figure 3). About 4 inches from the entrance of the 7-inch pipe into the box, the fumes of the substances listed were intro duced into the inflowing air. Spe cially designed pyrex glass flasks (figure 4), 7} inches long and with a diameter of 1$ inches, were used to hold the heated waxes. These flasks were made with a side arm and lube that extended to the bottom. The top of the flask was ground, and into this fitted a short tube 1} inches in length. This short tube was inserted into a large rubber stopper that fitted tightly into a hole cut out of the 7-inch pipe on the under side (figure 2). The flask in turn was placed in an electrie heater made to cover it completely below the side arm and ground glass top. Rubber tubing connected the side arm with a compressed air reser voir and a gentle stream of air blown through the melted wax kept it in motion and assured uniform heating. Into each flask was inserted a long stem centigrade thermometer which was kept in place and could be read at any time above the 7-inch pipe through which it passed (figure 2). Approximately 30 gra. of pulverised chlorinated naphthalenes or 20 gm. of chlorinated diphenyl were placed in the bottom of each flask and melted in the electric heater. Fresh samples were used every other day, but it was often found necessary to add 20 gm. of new material even after one run since so much had sublimed. Whatever the case, the collected sublimate was Ftc. 2. Electric heater for maintaining chlorinated compound! at a constant tem perature in place at inflow end of box. always removed from the upper part of the flask and a clean top used each day. No sample was ever used for more than two runs. The flask plus the contents was care fully weighed at the beginning of the run and at the end, and the loss in weight used to calculate the average I I I f l l 1 GBRN001939 luyiiwi'i-e TOWOLDMONOOOI504 288 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY \Stft. list rol. I amount in a cubic meter of air per flowmeter readings. The figures ob Dog minute as determined by a series of tained were not absolute because of slight variations in the air flowing eggs, T1 through the boxes and because of deposition of material on the ther begu expo mometers and on the inside surfaces of chloi the box, but they checked well with 16th j direct determinations through air com; samples. ; 18th Approximately 1 hour was allowed ! tive for the wax in the flasks to melt and j sure come to a constant temperature. At | kille that time the box doors were tightly . 15th closed, air bubbled through the flasks, and the blowers turned on. This was the beginning of the exposure period. Cox: By means of rheostats on the fans and dampers in the outflow pipes, the amount of air flowing through the boxes was adjusted and an attempt was made to keep the four boxes as 1 Fig. 3. Outflow end ol two boxca showing connections to exhaust system. uniform as [jossible--usually between 163 and 173 c.f.m. Trie tc In the first group of experiments the following substances were tested: Pent 1. A mixture of trichlomaphtha- 1 lenesplusa trace of tetrachlor- 80S napthalene. Chlorine content let 49.9 per cent. 2. A mixture of penta and hoxaehtomaphthalenes. Chlorine content 62.6 per cent. ! Chi \- 3. A mixture of 90 per cent penta and hexachlomaphthalenes plus 10 per eent refined chlorin ated diphenyl. Chlorine con 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 chlorina tion and also because of their industrial importance. In each instance 80 ani mals were exposed, 10 rats being placed in each cage. They were fed Purina : Per the ; gro exp for 1 16 Ea> cea 4:( we for ehi 6BRN001940 V TOWOLDMONOOOI505 tar ob of ing -e of her* - of tith air ned and At iitly and the the aipt as reen -the iha.ilor.vent rine "iita "-ties >rincvn- rine rcprinanrial ' nni;accd urine . t at. If, no. 7) EFFECTS OF CHLORINATED HYDROCARBONS 289 Dog Chow supplemented by lettuce, eggs, milk tad cod liver oil. This first group of experiments was begun on July 1, 1936 and the last exposure to number 2 (pesta and hexaehlomaphthalenes) was on November 16th. The exposure to the other three compounds ceased upon November 18th. On October 15th representa tive animals were taken out of expo sure from groups 1, 2, and 4 and were killed after 2 months on December 15th, in order to see whether this clear wax concentrations were aomewhat higher at the inflow end of the boxes. Preliminary runs showed that once properly adjusted, wax concentrations in the air remained very uniform from day to day, but to insure absolute safety readings of temperature, air flow, etc. were made every night be tween 10:00 and 12:00 p.m. as well as on starting and stopping. At dif ferent times during the course of the experiment tests for free chloride were made but were uniformly negative and Condition's Maintained in Inhalation ExrxHiurNT nos Jolt 1 to Komnn 18 and IS IUTB8U& CBLAHXI n, cemn at, coiiciinmnoi oritiwies TOTAt, SS* ' racu AT. ailt KX* ram % Trichloniapbthalenes plus traces of tctraehlornaphthAlene.................... 49.9 c. Me 150-180 1.21 ran#* High 2.60 Low 0.10 1296 loin 16 Pesta and hexaehlornaphthalenee.... 82.8 160-170 1.16 High 2.19 1864 Low 0.51 16 90% pesta and hazaehlomaphtha* leaes plus 10% chlorinated diphenyl- 68.0 165-175 1.27 High 2.17 Low 0.64 1896 16 Chlorinated diphenyl.......................... 65.0 165-175 0.57 High 1.19 1896 Low 0.23 16 period would bring about recovery in the affected fivers. Animals from group 3 were similarly removed from exposure on October 4th and killed for examination on December 4th. The average length of exposure was 16 hours daily for 6 days a week. Each morning at about 9:00 exposure ceased, and between this time and 4:00 p.m. the rata were cleaned, fed, weighed, etc. In order to secure uni formity of exposure the cages were shifted on a regular schedule, since showed that under the temperatures used no decomposition occurred. Table 1 shows the temperatures at which the various substances were held, the average concentrations per eubic meter of air, and the average exposures from July 1 to November 16 and 18. Theconcentration ofchlorinated naph thalene* and chlorinated diphenyl in (As air of workroom*.--Table 1 shows that have been exposed to varied concentrations of the substances under i t t II I it i i i t } * t i i t \ \ r ! I f i GBRN001941 TOWOLDMONOOOI506 290 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [Sepl. ttST test The concentration* 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 b question is passed over heated plati num b an electrically heated quarts tube and the effluent gas scrubbed b a column of glass beads moistened with carbonate containing a trace of sodium sulfite. The beads are then washed down and the chloride deter socnow NflTDeMMTBSCMJI rumM*tpn*f*osi*lmooooonI"s I5.Z4 aai * O.OOXS4 cm. Fio. 5. Dimensioeed 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 woe the work of Frederick B. Millhiaer and William F. Hemperly. The method and apparatus used for determining concentrations of chlorin ated hydrocarbons m air were adapted from well-known procedures. The air mined nephelometrically as silver chloride. Tebbens (1937) has recently de scribed a method and apparatus which should be equally satisfactory for this work. In figure 5 we show a dimen sioned sketch of the combustion tube and absorption apparatus as used by us b both our laboratory and field problems. The absorption tube is tot. it, no. 7] somewhat cash Tebbens's but devices are th in both ca=-. rinated hydro', acid and si.:. ( sodium carbon I In our case ci | apt to be ver; t less than 1 me i quently the at f actually forme. ! so small that r i either graving 1 For this rcasot. ( use the neph-?!;. | is sensitive to as 0.1 mgm. pc It is doubt; should exceed conversion ot pound to l:ysubsequent ab.Unless the Vi-'o low. .Another is that the m-: any chlorine;, determined. j distbguish be: I gases but deter 1 the results m { puted in tern: ! At the pre? ' formation a t ; rinated n&pbt! ' different plan: instances then repeated seve , the amounts 1 ( those used b f must be renv: 1 The eombef retus suited ta : by Willson Pr-. The equipment euetion pump wi 6BRN0019M2. TOWOLDMONOOOI507 Mb l. U, no. f] EFFECTS OF CHLORI? ATED HYDROCARBONS 281 omewhat easier to wash down than is have been exposed for 16 hours to an Tebbens's but the essentials of the two atmosphere constantly impregnated devices are the same.* with the substance under test, whereas In both cases conversion of the chlo human exposure is usually a variable rinated hydrocarbons to hydrochloric quantity, intense for a short time and add and subsequent absorption as then negligible. It is our opinion at sodium carbonate should be complete. the present time that the concentra In our case concentrations in air an tions of chlorinated hydrocarbons used apt to be very low--the objective is in our experiments would be dangerous less than 1 mgm. per cu. m. Conse for workers in the case of compounds quently the amount of silver chloride above trichlornaphthalene in chlorina actually formed in the final reaction is tion. Fortunately it is easy to venti so small that it can not be determined late processes of manufacture which either gravimetrieally or by titration. require these substances and to reduce For this reason we have been forced to air contamination practically to the use the nephelometric procedum which vanishing point. Such treatment of is sensitive to concentrations as low the problem at once removes both the as 0.1 mgm. per cu. m. of air. possibility of systemic poisoning and . It is doubtful if the sampling rate the annoyances that arise from cases should exceed 1 liter per minute as of acne. conversion of the chlorinated com pound to hydrochloric add and its Remit* of Inhalation Experiment*. subsequent absorption are not efficient 1. Animals exposed to a mixture unless the velodty of the gas stream is of trichlornaphthalenes plus small low. Another precaution to be noted amounts of tetrachlornapthalene. is that the method is not selective-- Living animals were apparently en any chlorinated substance will be tirely normal. Autopsies performed determined. Furthermore it does not near the end of exposure seemed to distinguish between solid particles and show slight swelling of the liver, and gases but determines them all alike and microscopic examination occasionally the results must, of course, be com bowed swollen and hypergranular liver puted in terms of total chlorine. oells. The changes were, however, At the present time we poaea in never more than slight. formation as to the amounts of chlo 2. Animals exposed to a mixture of rinated naphthalenes in the air of 30 penta and hexachlornaphthalenes. different plants, and in a of No abnormalities were observed in the instances the measurements have been living animals. Rata were killed and repeated several times. Frequently autopsied every 6 weeks. In the first the amounts have been greater than snimsls sacrificed liver changes were thoea used in our experiments, but it observed. These were swelling of must be remembered that the rata cells, slight granulation and hystinita- * The combustion sad absorption appa- } tion. In September and October these ntm suited to Said sampling is now mads conditions were somewhat more ad bjr Willson Product*, In*., Reading, Pa. i vanced, and in November the process The equipment includes floamatar and suction pump with a carrying eaaa. j became stationary. There were highly 1 BBRN0019M3 TOWOLDMONOOOI508 392 JOURNAL OP INDUSTRIAL HYGIENE AND TOXICOLOGY \Sept. im granular cells, hyaline inclusions and exposed to these compounds without mitotic figures, but no more than 2 illness of any sort. months previously. 3. Animals exposed to a mixture of The functional appraisal of the liver 90 per cent penta and hexachlor- damage caused by certain chlorinated naphthalenes plus 10 per cent refined naphthalene* and by chlorinated di chlorinated diphenyl No abnormali phenyl--There an 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 the injury so perfectly thalenes. 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. Hyalinixation 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 firtt 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 with trichloraaphthalene caused minor de arsphenamine, but somehow or other grees of liver damage, and no changes this now and then does happen to pa whatsoever in other organa. Then tients under antisyphilitic treatment. was no acute yellow atrophy or any It occurred to us that something of thing suggesting it except that a slight the same sort might be involved in this degree of liver damage was always problem. The human cases have been present and was quite clear in the liver scattered and few. They have been sections examined microscopically. isolated instances out of large groups This damage had no detectable effect of healthy employees who have hiui 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 theas people normally, being in every respect similar got liver changes such as existed in our to the many people who have been rats, changes not recognisable through l i i ! i i i 1 l I i i ! toL It, any m nation such e disturl not a which this r over t Knc had 1 slight we dc substf struct alcohc matio chlori per ki norm, to 0.' 0.75 < Tli tube niols folloT Rale . 1. 7 Mon 10. K 2. at 9:: 3 1 1 1 1 3. thole Fed raneww------ "" **" ..... ..... GBRN0019M4 TOWOLDMONOOOI509 A. ink i '937 ei. it, M>. 7) EFFECTS OF CHLORINATED HYDROCARBONS 293 Mt any means other then autopsy exami 1 died Nov. 10th between 8:00 and i; nation. If, upon the substratum of 10:30 p.m. such changes, they got an acute liver 8 died Nov. 11th between 4:30 aad 10:30 p.m. :er (d disturbance, acute catarrhal jaundice, not a very common disease but one 1 died Kov. 11th between 4:30 p.a. end 8:00 e.m. Nov. 12th. t! ii- which any of us may experience, would 2 died Nov. 12th eboat 1:00 m.m. er :ss this relatively innocuous disease go over to acute yellow atrophy? 1 died Nov. 13th between 5:00 and 10:00 p.m. 4. Chlorinated dipbanyl. Fed et 10:00 iin Knowing that our inhalation rats an., Kov. 10, IBM. 10 rati. rii- had liver changes, but changes too 1 killed Nov. 10th nt 10:30 p.m. (almoet iv slight to cause recognizable symptoms, dead). pt :ie we decided to test their resistance to substances known to cause liver de 2 died Nov. 11th between 4:30 and 10:30 p.m. 1 died Nov. 12th before 8:30 e.m. (stiff). i ;s struction. Carbon tetrachloride and 1 died Kov. 13th between B:30 and , alcohol were selected. Having infor 11.00 a.m. i in mation that 1.0 cc. of carbon tetra 1 died Nov. 16th between 10:18 p.m. -h -> chloride plus 1.0 cc. of ethyl alcohol per kilogram would kill 14 per cent of Nov. 15th and 8:00 sjd. Nov. 16th (tiff). Control*: Fed et 9:30 a.m., Nov. 12,1936. :d normal white rats, we reduced the dose 10 rats. 1 killed Nov. 13th for normal liver. to 0.75 cc. carbon tetrachloride and 0.75 cc. of ethyl alcohol This tabulation eummarizes into the This mixture was given by stomach facts that: - of tube to the following groups of ani 1. No norma] rats were killed by '.e mals and with the results found in the carbon tetrachloride and ethyl alcohol. ja following tabulation. 2. No trichlomaphthalene exposed rats were killed, and this finding agrees Halt Jtd O.lf cc. par bym. tack of carbon with our inability to find lesions of \e tetrachloride and ethyl alcohol by tiomach tuba ' moment in the livers of the animals y that inhaled this substance. .5 1. TriMornaphthalm* plu* tract pj Utro- 3. The penta and bexachlorinated jl eklamaphthalena. Fed it 9:00 *~m., Nov. naphthalene, the mixture of these with a 10,1936. 10 rats. No deaths. 10 per cent chlorinated diphenyl, and or 2. Penta and hcxachlornaphlhaUntt. Tad at 9:30 a.m., Nov. 10,1B35. 10 rata. finally the latter substance alone seem S died Nov. 11th between 4:10 and to have produced conditions lowering 10:30 p.m. the resistance to aa agent capable of 1 died Kov. 12th at 1:20 pjn. 1 died Kov. 12th at 4:30 p.m. 1 died Nov. 13th between B:30 and U:30 aa. 1 died Nov. 13th between sight of Kov. 14th aad 12:30 p.m. Kov. 13th. 3 producing serious liver disease. 4. The sole lesion produced by this test of liver function was scute yellow atrophy usually accompanied by jaundice. died Nov. 13th between 10:18 pjn. Nov. 13th and 0:00 m. Nov. 10th (stiff). 3. SO per ctni penta and htxacUornaph- thalenee and 10 per ctnl chlorinated dipbanyl. Fed at 10:00 a.m., Nov. 10, IBM. 10 rata. 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 we were able to find that was effective. GBRN0019M5 TOWOLDMONOOQ1510 294 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY UtT In animals with the minor degree of liver injury which ha* been described we were unable to produce acute yellow atrophy or any variety of liver effect with arsphenamine, cincophen, butyl chloride, ethylene chloride and tetra* ehlorethylene, but carbon tetrnehloride was uniformly effective in disclosing the existence of liver damage, Recovery from Uver damage following removal from expotvre.--Animals ex* posed to trichlomaphthalenes plus traces of letrachloruaphthsJene being practically normal on removal from exposure need no'consideration. In the case of the penta and hexachlor* sign* of liver injury will be many month* in returning to normal. The effect of high concentration* of trichlamaphthdUnet with trout of tetrachlamaphthalene.--The first group of inhalation experiments showed that this material in concentrations averaging 1.31 mgm. per eu. m. of air was relatively innocuous, judged both by direct observation and by the carbon tetrachloride test. This is an in* teresting fact since such compounds cause acne, though' less potently than substances of higher chlorination. In order to explore the matter further oneof theinhalation boxes was arranged ' TABLE 2 Cosditios* Maintaixxd tnnn bruunox os Hios CowcmmLiTiom or TaicmoaxApaTsaixxxs flu* TeraacaLOKXAPBTKAUifK ~-- AVo, CriDBMiiBrimeusnM EZTPOQTAtVLU SA9TE.TMOOAOTU c. m. TON* i**M W Trichlornaphthalenas plus traces of 137-300 10.07 High 16.49 tet raclilornaphthalene Low 5.78 1232 16 naphthalene, rata after 2 months' re moval from exposure still showed swollen liver cells, increased granu larity, hyalinization and mitotic fig ures. The condition was not advanced as compared with rats killed at the time at removal from exposure but on the other hand 2 months were insuffi cient for recovery. The same findings were true at the mixture of penta and hexachlorinated .naphthalenes and chlorinated diphenyl and for chlorinated diphenyl alone. Apparently the changes induced in tbe liver cells by these substances are exceedingly persistent and one must expect that an individual showing any so that fumes from four glass containera were delivered to the air line instead of one. This resulted in the conditions shown in table 2. The animals subjeeted to these conditions showed no clinical effects of any sort. After 1 month the liver cells were slightly swollen and over-granular 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 due condition were given carbon tetrachloride and alcohol, in some instances their livers showed massive central necrosis and . . ; j : ! ! ! ; ! j | | j I [ j j j : . . ; . ; . , in c rats one chlo 10X1 the} UP trat ** Pfn* The *KC hut Prt cou* not* Coxi Pent. atro; use On subj mar was the and sure then for kille. and expo kille* fattj with anim GBRN0019M6 TOWOLDMONOOQ1511 set. if, no. 7] EFFECTS OF CHLORINATED HYDROCARBONS 285 in others this did not develop. Fifty rats were used in this experiment and one may conclude that while the trichlomaphthalencs are in no degree as toxic as those of higher chlorination they are not entirely free from effects upon the liver if high enough concen trations are inhaled over long periods. The effects of high concentration* of penta and hcxachlomaphthalenc*.-- There can be no doubt as to the dam age done the liver by these compounds but in the concentrations so far re ported no symptoms were caused that could be recognized clinically and nothing approaching acute yellow the liver after 35 days of freedom from inhalation. It is thus evident that penta and hexachlornaphthalenes are markedly toxic compounds and that recovery from their effects is extremely slow. The effects of penta and hexachbrnaphthalenes, the mixture of these with 10 per cent chlorinated diphenyl, and of chlorinated diphenyl clone, when inhaled in low concentrations through an 8-hour day instead of a 18-hour day as in the first experiment.--Since steady human exposure to any of the compounds tested would invariably be for 8 hours rather than 16-hour periods, a further TABLE 3 Coxomoxs Maixtaixcs ncaixc Is'uutiom op Hig> Coxccwnunoxs op Pzxta and Hsxacklosxaputsalexxs ' a*.8cPt5K1e8cUrIa9uQnXos TOTAL *T. MbT mens ixrocu c. Penta and hexachlornaphthalenes......... 137-195 1.88 ffttfl High 14.0 Low 5.75 tort 608 lri 16 atrophy occurred except through the use of the carbon tetrachloride test. On December 1, 1936, 80 rats were subjected to the conditions sum marized in table 3. This experment was terminated on January 21. All of the animals lost weight and appetite and deaths began after 8 days of expo sure. Fifty-five rata died, most of them heavily jaundiced, 8 were killed for microscopic examination, 9 were lolled by the carbon tetrachloride test and 8 lived through the* period of exposure. The livers of the animals killed for examination showed marked fatty degeneration, central in type with necrosis of liver cells. Surviving animals showed pronounced changes in inhalation experiment was arranged under the conditions shown in table 4 which are quite comparable to those in table 1 except for the shorter inhala tion periods. Eighty rats were used for each of the three compounds tested. None at any time showed the slightest evidence of illness. Microscopic ex amination beginning after 6 weeks' exposure showed swollen liver cells, excess granulation, hyaline inclusions and occasional mitotic figures. These changes did not progress and were very similar to those in tire animals exposed for 16 hours under the conditions ask forth in table 1. The carbon tetra chloride test was uniformly fatal to them and one must conclude that coo- 296 JOURNAL OP INDUSTRIAL HYGIENE AND TOXICOLOGY ISepi. mi centrations of these compounds such s were employed cause a certain de gree of liver damage even if inhaled for but 8 hours daily. This injury is resisted successfully by the rats just as was the 16-hour injury but it is none the less there and destroys the ability of the animal to resist the carbon tetrachloride test. Summary of inhalation experiments. The findings that have been described briefly will be amplified upon the pathological ride in a further paper hy Dr. G. A. Bennett. What has been given is, however, sufficient to indi men never inhale enough of any of these substances to get acute yellowatrophy. They may, however, acquire a substratum of liver damage upon which acute yellow atrophy may de velop. Experience in a number of plants has shown bow easy it is to reduce concentrations of these com pounds practically to the vanishing point, and every effort should be made to attain such conditions. Gross Feeding Experiments The various compounds used were ground as finely as possible and mixed with a standard balanced ration for TABLE 4 Condition* MuniCRs ocaixo Iinuurtosr or low Coxccxteitions or Three CoitromoM ocaixo S-Hocx Ixsraao or 16-Hocx Pzbiooi iumuh ATo.rejaomaiwmiiMi izmmuru AY. DAILY ixmru c. MfVCTk Pent* and hexachlorniphthalence......... 148-183 1.44 80% peata and hexschloraaphthalenea plus 10%_chlormated diphenyl.......... 150-187 1.66 Chlorinated diphenyl.............................. 153-174 0.83 mo High 3.58 Low 0.42 High 3.30 Low 0.50 High 3.23 Low 0.03 Inn 820 912 820 bwi 8 8 8 cate that compounds more highly chlorinated than trichlornaphthalene 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 harmin very low concentrations and is probably the most dangerous. Industrial experi ence combined with these experiments make it appear probable that woric- the white rat. The food was placed in a single container, at w-hich the 10 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 give an idea as to the possible toxicity of the compounds selected and, if toxicity eras observed, some idea as to the rite, or rites of damage. The experiments were successful in both respects, and indeed one may anticipate that future appraisals of the possible toxicity of chlorinated hydro- . ; I i < - ; ml. h carbt feedi rate sary esscr in th by b< diffe seem so ft ever Ti tclra on unti ning to t and thre anin whic loss was; deat spin tion H slig' of g 2 Fee do;All wet 29, A logi affe tag, sioi the wa: l Fee dos GBRN001948 TOWOLDMONOOQ1513 itst ny of rellow rquire upon -,y de,er of is to comUhing made 1 were mixed .on for :ixs* .T, SUIT s 8 8 placed . the 10 chance, ; added of rats period. - to pve icity of loxidty the site ?sful in ne may .1.' of the i hydro Ml. I*. mo. 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 31 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 the fact that the those that have been described for different compounds so far studied tetra and pentachlomaphthalenes but seem to arrange themselves identically worse. so far as toxicity is concerned which SO per cent penta and hexaehlor- ever way they are administered. naphthalene* and 10 per cent chlorinated Trichlomapklhalene plus traces of diphenyl.--Feeding began May 4, telrachlomaphthalcne.--Feeding began 1936 on a 3 gm. dosage. On May on May 4, 1036 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 dying on June 8th. An autopsy the to the food for 10 rats each day, liver lesions were extremely severe and and this concentration was maintained of the usual type. throughout the experiment. All the On account of the high toxicity of animals were killed except the last the 3 gm. dosage, four rats were given which died on Nov. 2. There was no a 0.5 gm. dose every other day. Feed loss of weight and no appearance of ing began June 24, 1936 and the last wasting illness of any sort. The single animal was killed Sept. 11th. There death was due lu 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 Tctra and penlachlomaphlhalenei.-- gan May 4, 1936 on a 3 gm. dosage Feeding began oh June 29, 1936. A and was discontinued on May 10th. dosage of 0.5 gm. daily was employed. Seven of the 10 rats were dead t>y May All the animals sickened gradually and 12th. The three remaining rats were either killed or died by August gained in weight but were sacrificed 29.1936. for autopsy purposes on July 8th. At autopsy both grossly and histo The liver changes began at once. logically the liver was the single organ There were no changes in other organs. affected. The liver cells showed swell A second group of 10 rats was fed a ing, hypergranulation, hyaline inclu much smaller dose--0.5 gm. every sions and vacuolation. Here and other day. Feeding began May 20, there necrotic cells were found. There 1936. The first rat died on May 29th was a tremendous accumulation of fat. and four more before June 24th. The Penta and hexaddarnaphthalene*.-- remaining were sacrificed. Those rats Feeding began May 4, 1936, a 3 gm. that died showed losses in weight, dosage being used. By June 6, nine while those sacrificed had recovered i j i iI i I i f tI i i8 r i i j ii l i I i > I l l \ GBRN001949 TOWOLDMONOOQ1514 ktfBK 298 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY |5f*. IM7 their initial loss in weight and were gaining. The liver lesions were similar to those found in rats fed penta and hexachiomaphthalenes plus 10 per cent chlorinated diphenyl but not so marked. Summary of gross feeding experi ment*.--Of the various materials fed rats in large doses trichlomapbthalene plus traces of tetrachlomaphthalene was quite innocuous. Tetra and pentachlomaphthalene showed definite liver damage. Penta and hexachlornaphthalcnes 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 did 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 Dote* by Stomach Tube The compounds employed were sus pended in gum acacia. In figuring the dosage the total amount a man of 50 kg. would inhale in an 8-hour day assuming an air concentration of 20 mgm. 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 aune gum seeds 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 differences in the degree of effect but invariably the liver was the sole organ affected and the lesions were those already described many rimes. Discussion These experiments leave no doubt as to the possibility of systemic effects from the chlorinated naphthalenes and chlorinated diphenyl. As in the case 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 Tnxrkcd -and are -produced with the greatest difficulty. It is must 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 in the Inwra of ani mals very severely poisoned by penta and hexacbloraaphtbalenes but have found no increase 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 chlorin ated diphenyl eontaining 55 per cent of chlorine instead of 64 per cent as in the case of the experiments reported in this paper and on s compound with a chlorine content between tri and tetrachlomaphthalene. We an also determining the degree to which the diet may increase or decrease toxicity, this being suggested by amfiar work upon carbon tetrachloride. In the baas of these experiments K>1. II, and o) differs rooms tsinly that t more of thnapht compt are many plant; been 20 ye fact been hums Time chanj but t safe. m rar< hydrt safeg lead Coc* F t ( t F s 3 Fmx e 1; I Lcn i GBRN0Q1950 TOWOLDMONOOQ1515 ;.'J7 iCU- . m. .ore TitS res .bly .ted `dy .T'.St -rts and rase rree . the .:ing :eis rver the :irktnds iiver .aths rally ' anienta cave :ures, .isto.cted. :cting orin cent at as crted : with i and ; also h the ::ieity, work mente oT. It, no. 7] EFFECTS OF CHLORINATED HYDROCARBON'S 290 and on many field determinations of different compounds in the air of work* rooms, it appears safe and it is cer tainly easily attained, to ventilate so that the air breathed does not contain more than 0.5 rogm. per cu. m. of any of these compounds above trichlornaphthalene. In the case of the latter compound concentrations of 10.0 mgm. are permissible. We know from many examinations in many different plants that such roncentrations have been greatly exceeded during the past 20 years, and we are 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 utilising the chlorinated hydrocarbons are easy to hood and to safeguard. Compared with benzene, lead tetraethyl and many other com pounds, these substances are very little toxic and operations employing them can easily be safeguarded. It may be argued that where possible triehlomaphthalene should be used, but this compound will cause acne and if employed very carelessly might do more. Furthermore, higher chlorina tion is often essential for highly prac tical reasons. The solution consists in thoroughly adequate ventilation plus good housekeeping around all wax containers. A final word of caution bears upon the use of carbon tetrachloride as a wax solvent. Obviously this compound adds readily to the toxicity of the highly chlorinated waxes. If carbon tetrachloride is used, ventilation should be excellent, but in our opinion it would be better to dispense with car bon tetrachloride and depend on other solvents, especially upon those con taining no chlorine. BIBLIOGRAPHY CotntTOis-Scrm: Etude sur l'intoxieation profesiionnelle par le trichloronaphtaline. Ann. de mid. U(ale, 14, 423 (1934). Abstr. of paper by Tocauxx, A., axd MfotTBXL, B.: Dermatosea profesaionnelles par la aapbtaline et sea derivda. Prat. mtd. fraof., If, 335 (1934). Fumr, F. B., on Jaavxx, X. E.: Action of certain chlorinated naphthalenes on the liver. Proe. Soe. Expcr. BioL A Med., U, 118 (1936). Lmuxx, K. B.: Kurses Lehrbuch der Arbeita- and Grrerbehypene. 8. Hirtel, Leipzig, 1919 (p. 351). MimuTiDT, O.: GewerbeschSdigungen dureh Haftax (Trichlornaphtbalin). lnaug. dissert., Jena, 1935. Tzxaxxs, B. D.: Portable combustion ap paratus for field determinations of chlorinated hydrocarbons. Tarn J., It, 3H (1937). Txuxt, L.: Die Fernakraakheit (Chloracne). Klin. Wehnsehr., 9, 897 (1937). Tocbjliw*, A., Solettb, Mfxtraxi., B., asm Auabum: Cinquante-quatre cas de dermatitee par trichloronaphtaline. Bull. Soe. dsrmat. et typb., 41, 265 (1934). i GBRNOO1951 TOWOLDMONOOQ1516 300 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY {S*rt. I9S7 Discussion Dm. Cxcn. X. Dunks*: Vi havm bad quit* a longmorning, but line* Dr. too Oottinges has to tears, 1 am going to ask him to say a word. Dm. W. F. ton Omucoxx (Director, HaakeU Laboratory of Industrial Toxicol~gy, Wilmington, Delaware): I riih to con gratulate Dr. Drinker and his group on the very interesting and excellent work on the subject. I also wish to congratulate the Halowax Corporation on the fact that they didn't spare any effort to elucidate the prob lem so that the dangers which apparently are connected with the use of this material can be controlled. I personally believe that there is no tozie material which cannot be used safely if it is handled properly. In order to handle such materials properly during the different oper ations it is absolutely essential to be famil iar with the toxieity and especially with the mechanism of the action. Sinee there is no animal whieh corresponds in all its physio logical characteristics to the human being it is important that such compounds be studied with different species of animals so that one can get a cross-section of the poten tial dangers. In addition, this fset illustrates the im portance of the pre-employment and peri odical examination of workers in such work. As was pointed out by. Dr. Drinker, there are individuals who are apparently more susceptible to certain toxie agents than others. On the other hand, we have to try to detect the very first signs of incipient poisoning in order to prevent more serious damage. In the present instance it is very difficult to find there very first symptoms because there are no adequate methods, but I trust that in time the scientific profession will supply the medical profession with adequate methods whieh trill allow the physician to determine incipient damage of the organ before serious clinical symptoms become manifest. Thank you. i/lsrsMsMM Da. Cncm K. Drama: In this discus sion I will call on one or two individuals and I shall expect others to speak as their notes incline them to. First of all I shall ask Dr. Sayers if he will open the discussion for us. Da. R. R. Sanas (Chief, Division of Industrial Hygiene, National Institute of Health, U. 8. Public Health Service, Wash ington, D. C.): Dr. Drinker, Ladies and Gentlemen: It gave me a great deal of pleas ure to have the opportunity to listen to the excellent and interesting discussion and presentations made this morning. Dr. Drinker, and I might add, the members of the Halowax Corporation, have discussed this matter with us, as well as the manu facturers of the diphenyls.' We have been doing some work but not nearly as extensive as that carried on here. The work that we have been doing seems to confirm the work that Dr. Drinker has car ried on. I think there are certain parts of it that we can very well keep in mind. We are dealing with toxic substances, but we are dealing erith toxie substances each and every day in industry--harmful sub stances, hasardous substances. That these ean be controlled is well known, no matter what they are, and that we ean use them and we them in a safe manner. Dr. Drinker has called your attention to the fact that this apparently has been done and can be done in any of the plants where halowax la used. I have information from one or two of the other men who are in the audience that in plants where dasoage has been done --skin damage and apparently liver damage to some of the workers--the manufacturers have since corrected the conditions and ap parently have adequate engineering con trol supplemented with adequate medical eoctroi. After all, the proof of the pudding is in the eating. If the man does not get the dis ease your engineering control is successful. If he does get the disease, no matter what you have done in the way of engineering, you haven't been successful. We must go hand in hand. Neithsr profession alone can be successful. We have got to work together whether we like it or not. I hap pen to like it. Thera bone other thing. Aafarasmatw rials are concerned I think wo ought to bo V i .i. m rel. IS, a ! smart ent j eessfuily. adapted f it. Anot! vious to ii * flamn pproxima ay appro never just It might hit ere quite happened v with this it electric cql armor on th and was bei. Proximctcly to s steel rr bottom of th inspecting it hide exp-lam the fire kilici mine. Munj Here w<- h Now we have due to the t evaluate then I am informe not ju-t iUlt> fianunability chlorination h also increase* creases, aceor think that ch*> have these bar eoatrol them, we ean. . Ferhaps we c are better evi-r, present time 1 ; better. I arn w. submarines, it i noo-fiammaUe . . of their electrics Da. Ctca K.: you care to eay t Da. Alseet r f Occupation! neeticut DtpirtCoac.j: Dr. L:.-.. nnythiig that I *. l this material it f. I I 6BRN001952 TOWOLDMONOOQ1517 StfLtiST shall ul discussion "'vision of : stituto of ire, Washidies tad .1 of pleat* :en to the -iion and . .inf. Dr. ember* of discussed the manu- -k but not d on here. ..x seems to or ha* ear* part* of it .^d. unices, but inee* each -miul subThat these no nutter them and :.t. Drinker : fact that ud can be nslowax is one or two _e audience t been done ver damage ' -.nfacturcra ->ii and ap'cring eon* medical riding i* in cetthedis' successful, matter what engineering, *Ve must go isioo alone m>t to work uot. I hap* -- Isr is mateought to be I of. ffi, %o. 7] EFFECTS OF CHLORINATED HYDROCARBONS 301 nart enough to um every one of them suc cessfully. If this material is particularly adapted for a certain purpose w* should us* it. Another material that was used pre vious to this for insulation purposes, which was flammable, eaussd a disastsr in which approximately 187 men lost their lives. I asy approximately 167 because they wars never just sura whether it was 187 or 1(8. It might have been one or two more but they were quite sure that 187 lost their liver. It happened when they had insulated a cable with this material. They had an armored electric cable. It was covered with iced armor on the outside. It ws* 1300 fact long and was being lowered into a mine shaft ap proximately 3000 feet deep. It waa lashed to o steel rope. It slipped and fell to the bottom of the shaft. When tha foreman waa inspecting it he act it on firs with his car bide cap-lamp. The carbon monoxide from the fire lulled those men that were in that mine. Many erf course escaped. Here we have one hazard, a fire hazard. Now we have another one, a health hazard due to the toxic materials, Wa have to evaluate them. Certain of these materials, I am informed, art also flammable. I am notjust aura how flammable they are but flammability probably decreases as your chlorination increase*. But your toxicity also increases aa your chlorination in creases, according to Dr. Drinker, and I think that cheeks with other findings. Wa have these hazards to balance but wa can control them. I feel quit# coofidant that wa can. ' Perhaps we can find other substances that are better even than this material. At tha present time I am advised that wa have no better. I am advised that in ships, such as submarines, it is quite important to have a non-flammable substance for the insulation of their electrical wire. Dx. CxcmK. Duurxxm: Dr. Gray, would you care to say a word! Da. Albuxt 8. Gaav (Director, Bureau at Occupational Discs***, 8tat* of Con necticut Deportment of Health, Hartford, Conn.): Dr. Drinker, I don't think thorn is anything that I emu say except that we ussd this material in Connecticut and ws had a number of so-called eases. AO I eu say is a confession of ignorane* on our part at that time and I was very glad to toe that your digging into tbs literature as thoroughly as you have hasn't elicited any further infor mation than wo were able to get, basically. About all we could find was about tha two cote that our friend, Lehmann, experi mented with. We got in touch with him and ho eonfeooed that the amount that he had given the cats and his method of determin ing it were probably subject to very serious scientific criticism, and we agreed with him on that point. We felt, and I am very glad that it is what you feel as a result of your experiments, that if we put in an efficient ventilation sys tem sufficient to prevent the dermatitis, we probably wouldn't have liver damage. That ia what we did entirely empirically. I think that is about all I have to say. I have been delighted to be here sad to have as many members of my staff here as I could jack out of the office. We have been de lighted to listen to the discussion. D*. Cecil K. Daman: May ws now make the discussion general and those who have questions plaaaa volunteer. Mb. Mjlxvbxd Bowoitcb (Director, Division of Occupational Hygiene, Massa chusetts Department of Labor and Indus tries, Boston, Mata.): I would like to second very strongly what Dr. Sayers has said with regard to tbs approach to this problem in proper control rather than by prohibition, whieh seems to me wholly unnecessary not only in this case but in the ease of other toxie substances withwhich ws have to deal. The problem of proper ventilation seems to me relatively simple from what I have heard of the situation thus far. The problem of maintaining that ventilation properly does not seem to ms quite so simple. I think it is going to be quite necessary that there should bs a very adequate inspection of the plants using the materials and I can assure you that that will bo the com here in Massachusetts. When this trouble first broke in this state o little ovtr o year ago wa issued o quite strongly worded waning letter to all plants using then* subotaneao and it has all along i t t t if I ii.i, i ii ji in if..i x -! MJiiwiiii.,tqn 6BRN001953 TOWOLDMONOOQ1518 30? JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY IStpt. JUT been my pita to follow that up with fur ther letter bringing the rituition aa we bow know it, ee a result of Dr. Drinker1! work, to the attention of users in this state. In that letter we shall unquestionably advoeate the concentrations that Dr. Drinker has suggested this morning. One point that I think is worth commentfog on in that connection is the question of identification of the substances. It is ex tremely important from tbe state adminis trative point of view that employers using these substances should know what they are using. They are identified at present only by numbers. It we list those numbers in a warning letter which a'e send out there are likely to be changes in those numbers. The Halowsx Corporation it a progressive con cern and it is going to be putting out bigger and better halowaxes all the time. The 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 cay anything about that. Mb. 8Axnronn Bnowx (President, Halowax 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 eheraieal 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 bo toxic. The problem to far ns 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 9BBJOOO an research to determine whether or not it is toxic or should you wait until you have determined whether you have amarket for it? If you axe producing only one hundred substances a year yon can see that h* would run into boxcar numbers In the way of dollars and cent* before yon ever sold any. That is tbs problem wo have had in this ease. It has been on the market for 25 yearn. Until within tbe past 4 or 5 years there bn* never been any intimation that it would causa any systemic effects. Thou sands and thousands of workmen have dealt with millions and millions of pounds of cer tain of these materials, particularly the trichlomaphtbalenes. Then we come to the higher stages, combined with chlorinated diphenyl and other products, and suddenly this problem is presented to ua. We had naked various authorities in terested in public health, going back over n 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 aa these changes are con cerned, they are beyond our control to n certain extent. We will manufacture a product--let's call it 1234. It has certain chemical and physical characteristics. It ia supplied to a cable manufacturer. It ia composed of certain eoosiituenU. There may be some tetraehlornaphthalene, triehlornaphthalene, paraffin, a little pitch or bitumen, and possibly some chloriuated 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. Poaaibly by n change in thoae constituents of only 1 per cent we can get that particular property. We can't aell it to him aa tbe same product to we put a new number on it. Basically, however, if the variation in the chlorinated naphthalene or the chlorinated diphenyl constituent hasn't changed, the toxic property of that will not change. When it comes to n question of cooperat ing with the stats authorities in that con nection, if them worn some major change mad* in n product wo would have no hesi tancy in advising them and we would also advisa our customers. Virtually every con sumer of these materials at some time or another has been given their technical or chemical designation along with their vari ous properties, whether they ho physical or chemical. Those art some of the practical problems I 6BRN001954 TOWOLDMONOOQ1519 Ml. U, no. 7] EFFECTS OF CHLORINATED HYDROCARBONS 808 with which all manufacturers of chemicals ara confronted today, particularly in the synthetic organic field where the develop ment is so rapid that our sales departments can't even keep up with the research depart ments sometimes, in knowing what they are doing. Mb. F. R. Kaimxb (Assistant to Man ager, York Wireworks, General Electric Co., York, Fa.): I am certainly pleased to have this opportunity to tay a few words with reference to the experience we have had at our York plant. I perhaps should say that again in this case experience alone has been the beat teacher. I have lived with the problem at York with the men who went through the experience from its beginning. It is only 1| years ago that we had in the neighborhood of 50 to GO men afflicted with various degrees of this acne about which you all know. Eight or ten of them were very severely afflicted--horrible specimens as far as their skin condition was concerned. One man died and the diagnosis may have attrib uted hit death to exposure to halowax vapors but we are not sure of that. There was an atrophied condition found as a result of the autopsy but we are not definitely sure that it was or was not connected with his work. Knowing the nun as I did when he was employed, with the'superficial examina tion that he had. be appeared to me very thin, pallid in hia appearance, and I would not tay from my poor knowledge of the physical make-up of the human being that he presented a healthy appearance. How ever, it was only for a 6 months* period from the time of hia employment that ha com plained of this constipated condition and we advised that he see hia home physician. It rapidly developed to ths point whom be was in the hospital and in a vary short time he died. Mors serious than that perhaps is ths fact that we had 80 other man in very bad condi tion as tar as the acne was concerned. The flint reaction that several of our executives had was to throw it out get it out of our plant. They didn't want anything like that for treating wire. But that was easily said but not so easily done. We might just as wall have thrown our business to ths fourwinds and said, "Will close up," because there was no substitute and there is none today in spite of all the efforts we have made through our own research laboratories to find one. But we did develop--and I was moat closely associated with it--end set up a routine for bringing these men back to nor mal health conditions. A number of them were sent to Dr. John H. Stokes and to Dr. O. H. Perry Pepper of the University of Pennsylvania Hospital, and ths others to Dr. Isaac R. Pels at Johns Hopkins. Through their recommendation! and studies we employed a trained nurse and two local phyaieiana and you might any established a small hospital and its facilities at the plant. Through the application of quarts light, x-ray, mechanical removal of comedones and the treatment of pustules that de veloped in later stages, an utterly strict routine where the worst cases were adminis tered to each day for a period of 15 to 20 minutes, another group who were less seri ous three times a week, and still another group once a week, we have in this year and a half brought each and every man back to a normal akin condition. TIiom who were very seriously afflicted do show scars, but otherwise their skin is as healthy in appear ance as my own. I tell you we are very proud of the fact that they are still all em ployed and the amount of halowax that we are using today is even greater in quantity and in types than we were using a year and a half ago. With the adequate ventilation system we have installed, with the routine for change of elothing from street clothing to work' clothing when they eome to work and the reverse of that process, with the assurance that a shower will be taken before the street elothing is again put on, we have found no recurrence of this skin trouble. Each and every man working with halowax products, either from solution, from solid compounds or handling the wire insulated and treated with it, is examined twiceyearly with a com plete physical examination, including blood analysis and efforts to determine any liver damage. However, there is the point which waa very definitely brought out this morning. We do not know as yet when this thing starts. I believe it would be of great help $04 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY f*yf. iSil to us all in industry if torn* very funda mental work woo don# on humans, as Dr. Jones mentioned before we came into tbit meeting, tome control in fundamental work to determine tome method whereby wo may determine the inception of any liver dis order. We haee had our man examined in groups three timet tinee the trouble developed and nothing hat thewn up in any one man. We have learned and appreciate the fact thatwe mutt handle hazardout materiala, but we have learned how to handle them. It has been a very great experience for ua and for mytclf, and again the beat teacher. Da. Cecil K. Dnorua: Can you recol lect the air concentration that you are main taining now with your present ventilating equipment! bin. T. R. Karma: We have had two examinations made of the air by Mr. Wil liam F. Hemperly and they average from 0.2 to 0.6 mgm. per cu. m. We recently dis covered one condition which waa found at the cause of a high reading in one of the examinations. The compound it one that it not manufactured by the Halowax Cor poration that it used rather infrequently, perhape not more than SO gallons of it in a 6 month period. Itit 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 recults off to a high value. It was then about S mgm. pereu.m., I believe. That it going to be eliminated now. That it a combination of toluene and carbon tetrachloride solvent. When that compound is expound to the air the chlorin ated solvent odor it completely masked by the toluene. Itit lost. I was able to detect it only by removing the head of the drum Immediately iMffing the odor rj carbon tetrachloride. Aa toon at that head was removed for a period of 10 seconds the toluae predominated and ere had no knowledge of the other being in there. Ua Amn Q. Bara (Research Engi neer, United American Botek Corporation, Springfield, Mast.): Do I understand you to any that those men who wort affiieted are back on the tame job! Ua F. R. Karma: They all returned to normal skin health, aa I say, and are work ing on the same Job. Da. Caen. K. Daman: Dr. Schwarts, you have teen a good deal of this general subject. Da. Louts ScawAUTS (Medical Director, Dermatoses Investigations, United States Publie Health Service, New York, K. 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 eases of yellow atrophy of the liver attributed to halowax. I can only talk from personal experience about the skin eases. I know from what I have seen and from what I have heard from doctors who have been treating these cases that if they are treated like aa ordinary acne vulgaris and kept away from further large exposure they all get well, with the same results aa sene vulgaris. Those who have large pus tules may have scare resulting and those who have superficial pustules or only come dones won't have any sears. As far aa 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 fat Pennsylvania when this waa discussed. About ventilation and safety precau tions, I think that while we cannot, with our present knowledge, detect by any ehemical tests the early symptoms of intoxication from this substance, the skin offers as easy way of proving whether your method of ventilation is efficient or not. If there are any eases of sene or of this dermatitis occur ring in a plant whars halowax or the chlorin ated naphthalene or chlorinated diphenyls are used, then that shows that Acre is suf ficient concentration of these substances fat the air to cause plugging of the fotUelee and to cause a akin condition. If there is suffi cient concentration to do that these may be * t GBRN00195A t i TOWOLDMONOOOI521 a of. 18, a*. n EFFECTS OF CHLORINATED HYDROCARBONS 305 sufficient concentration to enw ijrilmiin poisoning in tbe It* people who nre hypersent:tire to tbe action of these hydrocar* bons. Everybody is not hypersensitive to them. It they were, of the thousands of people who have been handling these sub stances, more would have contracted this disease and it would bare been reported very much earlier. This material was used in Germany as early as 1914 or 1915. While I cannot add anything to tbe methods outlined here for safety in the way of ventilation and so forth, I can say that if. you go into a plant and find that there is any acne present among the workers with this material you will know that there is sufficient of tbe substance in the air to cause acne and consequently sufficient perhaps to be dangerous to the few people who are hypersensitive to its action. Da. Cecit K. Drinkib: There is a prac tical point in regard to tbe 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 baa seemed desirable to a number of the men who are here that during tbe 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 tbe subject: perhaps, Mr. Cook, you have an idea or two about that. Ms. Waisdt A. Coox (Chief Industrial Hygienist, Bureau of Occupational Dis eases, State of Connecticut Department of Health, Hartford, Conn.). On the deter mination of tbe belowaz I wonder if it wouldn't be preferable to have Mr. Hemperly discuss the method he has been usiag throughout the country for the determina tion of chlorinated naphthalenes. Da. Caen, K. Daixaaa: I think so far aa that is concerned it is beet to leave that to discussions with Mr. Hcmperly and Dr. Brandt afterward. But the question of determining some uniformity of technic for a while at least is, I think, a matter of gen eral interest to us. Mb. Wsanax A. Cook: I am net quits sure that I have in mind exactly what you want in that regard. In connection with amplingT Da. Cecil K. Dxwkxu: Yea, In con nection with the whole technic of determin ing tbe 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, aa they will in tbe eourse of the next couple of years, we will at least have them on a comparable basis. Mb. Wabbxx A. Cook: In that regard there is no question butwhat the determina tions and results of analyses of the concen tration of injurious materials in air, corre lated with pathological findings or freedom from pathological findings, are real factors in further substantiating toxic limits whieh 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 wbat 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 many of the organisations equipped to make determinations of injurious materials in air should do, is to make aa effort to develop one group and series of results whieh 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 sir to determine maximum exposures, to get the exposure over a 15 or 90 minute period when the worker may be actually tending a pot where the material is being used, whereas during tbe 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 bo extremely desirable to obtain in formation in as many plants and as many loeatiooa as possible of the average expo sure, taking into consideration not only the worker's maximum exposure white actually j i BBRNOO1957 TOWOLDMONOOOI522 308 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY IStpl. 19S7 at work with these nutcrlilt but also his much amallcr cxpoaura and poaaibly even lack of expo*ure aa he may go to other part* of the room or even to other departments during the eouraa of tha day. Another type of determination which seems to be extremely desirable to have ia concentrationa of the chlorinated naph thalenes at certain reference points. I believe that Mr. Hemperly very carefully duplicated these reference points in each of the plants where he took his determina tion!. 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 dogged 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 tiie 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 ars making those determinations these reference points so that in 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- edgs 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 unto consideration. It seems to mo that it aright be a very desirable project for that committee to consult with the in vestigator of the Halowax Corporation and suggest to ell of those who are doing work of this type, after some discussion, what reference points eould be sdopted and also what should be done in connection with get ting these average exposures. As a matter of fact our committee will diseum that very feature and possibly include it ia our report before the A. P. H. A. is Oetobar aa one of the projects which ws shall cany 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 be. We have a real problem hers and one that deserves some study. Dm. Cecil K. Dxixkes: Would it be of service to the American Public Health Asso' elation Committee if a sub-committee from this meeting, collected perhaps by my brother and those of you involved with these problems, were to make a recommendation to the A. P. H. A. as to the things you have brought up and aa to suitable apparatus, and let tbs final statement come from tbe Association after they have considered that material? Mb. Wua A. Coox: I think that would be a splendid idea because we have a bulk of information on this particular material. A number of individuals have given much thought to tbe development of apparatus, both the combustion method whieh 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 subcommittee 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. R. Hayhurst, W. F. Hsmperly, F. W. Sehl, and A. N. Setteriind.) Mb. Hxavxr B. Euuxs (Chemist, Divi sion of Occupational Hygiene, Massachu setts State Department of Labor and Indus tries, Boston, Maas.): In connection with what Dr. Schwarts has said, I am not sure that I am ia complete agreement as regards the use of skin lesions aa warning agents. It is my understanding that ia insulated wire plants the chlorinated diphenyls are very commonly compounded with tha chlo rinated naphthalenes. It is also my under standing that these are more likely to cause a severe skin irritation than the straight chlorinated naphthalenes. On the other SBRNQ0195B V. ASMUUagUMi TOWOLDMONOOOI523 wd. 19, no. T\ EFFECTS OF CHLORINATED HYDROCARBONS 307 hand, from Dr. Drinker** work one would Judge that the straight chlorinated naph thalene wm nearly aa toxic at least as the mixture of it with a email amount of chlo rinated diphenyl. In the eondenser factory where we had our eaaee there is no chlorinated diphenyl used and no acne of the type described in the reports on the insulated wire factories. Da. R. Eimirt Kellt (Monsanto Chem ical Co., St. Louis, Mo.): I can't contribute anything to thelaboratory studies but there has been quite a little human experimenta tion in the last several years, especially at our plants 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 systemie reactions at all in our men. We have examined them very closely both from what laboratory tests we thought might help us sod from the clinical view point. Also from chlorinated diphenyl alone there have been no esses of systemie poisoning reported. I don't believe that we can transpose the laboratory results into the actual humans without paying considerable attention to the volatility of dilfe'rent substanees and the way they are being used. Da. Jobs* A. Hooxet (Consulting Der matologist, Halowax Corporation, Detroit, Mich.): I have bad considerable experience with the dermatological angle of thia prob lem. The experience at the Halowax plant at Wyandotte definitely waa that the derma tosis did increase when compound* were used rather than the straight chlorinated naphthalenes. From the discussion wa have heard today I think the observation Dr. Drinker made that the ehanees are that dermatological problem* will disappear along with the other is probably true. However, I think that certain precautions, certain insurance meas ures, you might say, should be taken in hiring men who are going to work with these products, even though we are going to attempt to get the concentrations low. We saw this morning that the effect of these produets was on the liver and that if some one working in these products developed liver damage from some other source the ehanees of his having serious trouble was increased. Therefore, inasmuch as there is no test to tell whether a person has had liver disease, eertainly in the preliminarymedical examination of applicants for work the his tory at least should be gone into very care fully for a history of previous liver diseases. Thar* are other things that should be taken into consideration also. One is the history of syphilis, beesuse 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 oh men at stated intervals, because they might develop syphilis after they are hired. I think those things should be done even though we feel that if the concentration of these vapors in the air it kept as low as was recommended this morning, the chances of having toxic effects are very small. Mn. F. R. Klines: 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 ehloronaphthalene 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 chleronapbtbalene orwas 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 ehloronaphthalenss are leas harmful in so far aa acne is concerned or is it because of the handling of batch compounds? Dx. Jokx A. Hooxxt: 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 eases after I started working with tbsm the man in the plant said i i wwwencgi .1 nwip SBRN001959 w TOWOLDMONOOOI524 308 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY 199T that they developed acne more often and vulgaris is most apt to ooenr. The sebace more severely after they started making ous glands are moat active and they seem to compound*. It may be that it was in the have it much more than the older people in method of the handling. whom the eebacooua glands art not so active. UaF.EKtnmi: You lay that the con Ws keep n dipping of all articles relating dition increases with the increased chlorine to industrial dermatitis in my office and 1 content and we are attributing the acne pri recently rend an article la a German mega marily to the chlorine radical. If that is sine in which they report in Germany a true, what are we to associate insofar as similar sene condition from chlorinated these various other constituents are con phenols and chlorinated benzenes and solid cerned, such as various plasticising agents? wax**. It seems that this acne-like condi t How much do we know about those insofar tion is not peculiar to halowax or chlorin as development of acne is concerned? Some ated naphthalenes or diphenyls but can of these compounds have a half dozen con occur with sny condition that blocks up the stituents in them other than rhlorodipbenyl sebaceous follicles of the skin. and ehloronaphthalene. We are at the present time considering the chloronaph- Da. Rotax. Mxxxxm (Special Agent, thalene as the basic element responsible for State of Connecticut Department of Labor, the acne condition which we have. We Hartford, Conn.): I am full of question*. know very little about what the other mate As a statistician I am n little hit suspicious rials may or may not do. of averages, so I should think that we should take maxima as well as averages in getting Da. Jose A. Hooext: I don't know at tht threshold dose or the dangerous im about these other materials. Perhaps Dr. pregnation of the atmosphere with these Schwarts would know something more poisonous compounds. 1 just wanted to about them. drop that as a hint for this committee to consider in its work. Dn. Locis Scewaetx: It is well known la spit* of what you said at luncheon, in industry that there are many compounds Dr. Drinker, I still think it is rather impor that cause acne. For instance, paraffin tant to determine how the plugging of the acne* .and oil senes have been known for a pons actually doe* occur, whether they an long time. Paraffin acncs, was acnea, are plugged aa Dr. Schwarts ha* suggested, simply a mechanical plugging of the fol from the particle* falling on the outside of licles of the skin by the minute particles of the akin or whether they an plugged, aa so wax that fall on the skin. I think that the many doctors haw informed me, from inaid* acne caused by these chlorinated naph aa it ware. The fumes an breathed, the thalenes and diphenyls, because it is caused substance gets into the blood stream. It it by both--I was down at the Swan Chemical throws off through tho pores of the skin and Company where they make chlorinated di the pons an plugged. I think it it rather phenyls and they have acne there just the important to determine that because it same asover at Wyandotte where they make seems to mo, from the slight knowledge that the chlorinated naphthalenes--I believs I have of the industrial application of halo- that that is caused by the same thing, n wax compounds in insulating wires, that blocking up of the follicles of the akin, the the plugging of the akin, if it is just aa out- formation of the eomedona and than the aid* plugging, may taka plaet cither from eomedone becomes infected and forms a handling a solid substance or from the pustule. They don't all pustulate because coating on tho win after it becomes cold. they don't all become infected. Many of I haven't heard anybody my anything these men never have any pustules. They about them hfanaehuaettu eases of wry just haw Uttle white elevation* on their sewn dermatitis and I am not so sun but skin. what then was sums question of liwr dam In tboee people who are in the sen* age, age then. Nobody has said anything about the youngsters of 18, SO, 8 and 9, sens them at all. Thar* is aa question thaw tha tioi coli I Dr. hav cur tbs hot 1 exp eat and left h; pou tot be < pic: Mr Coi it. salt Clin all < rat: cat: or i und nti 5 Gen Cor vec hell bee in a of v lure fact ben U rent veu' fum COB) inst tog out W else wax seqt BBRN001960 I TOWOLDMONOOOI525 el. 19, as. 7] EFFECTS OF CHLORINATED HYDROCARBONS 309 that the condition, whatever the complica tion* might have been, came from handling cold wire, in a confined area of eoune. I think this need* a great deal more study. Dr. Drinker, than you and your aaaoeiatoe have been able to give it ea yet. All I am eurioua about ia the way we can adainiater the protective labor law* ia order to protect both the employer and the employee. I listened with very great interest to the expositions of suggested pots for the appli cation of halowax, chlorinated naphthalene and diphenyl. It seemed to me that they left very much to be desired- I don't tee why the application of the halowax com pound, if it is necessary, as I assume it is, to use this rather dangerous substance, can't be done ia a practically closed pot. U you please. Dr. Drinker, I wish you would ask Mr. Reeves of the Rockbestoe Products Corporation to tell how they have handled it. If I am any judge of equipment and safety devices they have come as near to eliminating eotirely from the atmosphere all contamination from fumigated or evapo rated halowax as anyone. All of the appli cation of halowax, either in the melting pota or where it ia applied to the wire, is done under hooding and with ventilating appa ratus, and it seems to be entirely adequate. wax we had a head start as far as the ventilating system eraa concerned, sines ours was already installed and adaptable to s compound with a benzene solvent rather than smelted halowax compound. Inorder to keep the fumee of a highly volatile sol vent under control we did develop a prac tically eomplete enclosure for the container in which the compound was placed and exhausted tfaet container in order to prevent any escape of the fumee from it. When we changed to the halowax compounds we fol lowed the same scheme of applying the compounds and used a completely enclosed pot. There is a hole in one aids for the wire to go in and one on the other aide for the wire to eoma out. There is enough exhaust suction on the enclosure to prevent any fumes from getting out of the openings where the wire enters and leave*. Of course periodically it is necessary to open the pot to replenieh the compound or make adjustmenta. In that ceee we have the ventilat ing eyitem interlocked with the door that the operator opens so that whan he opens it he increases the amount of air travel about ten-fold. Dm. Rotzl Mxxcxa: What it the veloc ity when the door is opeaT Ma. B. H. Rrrvra (Vice-president and General Manager, Rockbestoe Products Corporation, NewHaven, Conn.): I will be very glad to tell of our experience if it will help the picture along. Our experience has been more or lest parallel with Mr. Kabner's in aa much as we manufacture the same type of wire. We have avoided the serious pic ture that he ran into, probably due to the fact that shortly after 1933 we were using benzene as a solvent for asphaltic materials. We got into anemia difficulties with ben- tene fumes and had to install a complete ventilating system to remove all those fumee from the machines that applied the compounds to the wise. Following the tnatolUtion of thatequipment we were able to gat a substitute for benzene, so we got it out of the picture. ` We are still in the same fix aa every one else is aa far az finding a substitute for halo wax. Than tenons that ws know of. Con sequently wham we wsat to the urn of halo Ms. B. H. Recvts: With the door wide open, at breathing level the velocity ia 300 feet. That te the linear velocity. We cheek that every week on every opening at every machine with a velometer, a email instrument which is easy enough to operate and reads directly. Whenever the velocity falls below that figure the pipe connecting that machine is taken down and cleaned, because there will be condensation inside the pipe to cut down the air flow and reduce the ventilation efficiency. Da. Rotan Mxxcxa: What do you think of that trap device ehownf Ma. B.H. Rxsvns: I don't know what to think of that I don't know whether it would be practical or not I was going to ask Dr. Drinker whether in pooling the sir laden with halowax fumet through the box* of rats then was any deposit of halowax in tho enclosure. -- 1 i j 1 --------j . ft -in-ftv---- ----------- - 310 JOURNAL OP INDUSTRIAL HYGIENE AND TOXICOLOGY (tp(. IM7 Dm. Cktl K. Damn: Yes. It is detectable tttdil; through the outflow pip*. Mm. B. H. Rxxrzs: Those im tb far mmd probably didn't get tho concentration. Dm. Cecil K. Dmixmcm: Wo change tho pooitioa of the bom each day. The one* furthest away more into tba nearest posi tion, so that over a period of weeks all are exposed equally. compiiints were bona fide. We hadno dif ficulty in handling cold wire end the men had no skin trouble. Yet when they did tho tame thing with possibly tha application of boat in tunnels, ship* and so forth, they actually did develop trouble. We have used, of course, the icterua index In following some carbon tetrachloride eases and I wondered whet you have to say about that. Ia that of ae value at all in the ease of liver damage ia this material! Dm. Emeut R. Harvcnn (Consultant in Industrial Hygiene, State Department of Health, Columbus, Ohio): 1 would lih* to ask if it wouldn't be possible to put a cold water line around that trap and deposit it all before the air escape* from the trap. him. B. H. Rxsvxs: We have tried tool ing the surface of the exhaust pipe* in order to concentrate the deposit in one place and make it unnecessary to remove long lengths of the ventilating system. While we have found a alight advantage in doing so it hasn't at all paid for the expense. It is much easier to take the piping down. Con sequently I doubt the possibility of remov ing it all by moling the surface* of the trap. It might be possible, by building a labyrinth of refrigerating coils, to collect it. But then you would hare the problem of remov ing it from the coil* after you had collected it and it would involve rather complicated procedure. - * * Dm. B. L. Vossumom (Medical Director, Ccneral Electric Company, Schenectady, New York): We have heard about tb* pos sibility of preventing liver damage and skin trouble among manufacturer* of wires and cables and so forth, but like the old rhyme, every dog has fleas and the fleas have fleas, we also have customers who-use wire* and cables im tunnels, in enclosed (pace*, splic ing them together and doing all aorta of things. I am not at all certain that we know what ths concentration of theee chlorinated hydrocarbons is under those conditions. About the time we were having no much trouble at our York factory some of our customers began oomplainfag. Ws thought we were having a hysteria of balowex mania throughout tho country. Some of their Da. Caen. K. Daorrxa: I don't think so until it gets so extreme that we know it any way. Da. B. L. Voenuaon: I did write down n few questions that came to mind. Some of them have been answered end some are foolish but I (hall ask them anyhow. It occurred to me that if triehloraepbthaiene has been proved to be practically innocuous, isn't it a problem of research largely for the Halowax Corporation to use only that one material adopted with other known chlorinated compounds to meet the requirements of customers? That ia one of the foolish ones probably, but I shall just ask it. Furthermore, how long is it reasonable to expect the liver to recover after it has been pretty well damaged. I talked to you and you said you hadn't worked that out with tha animals as yet. Da. Cxcil K. Dbixsxb: In that earn we set eaide a certain number of animals to recover, after knowing that a certain amount of damage had been done. Then we started to kill them but we invariably ran out of rata before they ran out of lesions. Wa don't know how long it lasts. Da. B. L. Voaacmox: Have you given them ealeium and glucose as you would with carbon tetrachloride? Da. Caen. X. Dmxxan: Not yet, but we art doing an experiment now with one group co a very high ealeium diet and another group on a ealeium free diet. The whole question of ealeium ia the diet, of giving mBk daily to theca people may be worth while. vol. 1 D queS' what bflit: chlo; M imp from the t I tbi toot thet The indu. chlot T1 whic our ] will Drill dem: comj some we c remc uent and a lot able one A: with theti some coroi quef the wlie to 1( r. so111 the D mor. on s. all ^9 GBRN001962 TOWOLDMONOOOI527 eel. Jfi, no. r) EFFECTS OF CHLORINATED HYDROCARBONS 311 Dn. B. L. YonsMi: I just had thou syphilis during the time they are working question* in mind. I would like to hear for you, you are probably going to lose some what Mr. Brown would sty as to tbo possi very important employees. It would eeem bility of using only this one innocuous that it would be worth while to give serious chlorinated naphthalene. consideration to seeing that conditions are Mn. Saxsronn Bbown: That would simplify our problem exceedingly, not only from the commercial standpoint but from the toxicity standpoint. But if we did so I think that Mr. Kaimer would be the first to object becauu he wouldn't be able to get the technical effects he desire* in the cable. proper and suitable for them to continue working for you and that they have proper treatment. In other words, I don't believe that is a good or sufficient reason for dis charging those employees who do develop syphilis. We have not found that to be true in other places and I question whether this is one of the places. I msy be in error. The same thing applies throughout all the industry where we are using these higher bin. Sakovoeo Bbowx: I want to take chlorinated products. this occasion to express on behalf of the The problem as wc see it, and it is one Halowax Corporation my thanks for the which we intend to study further (we have excellent cooperation we have received from our program for this continuous work that varioui state authorities and our customers will be done under the direction of the as well in this investigation. I believe you Drinker brothers), it to try to find a line of ' have all formed the opinion, based on what 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, some one thing that causes the trouble. If scientific and constructive basis. 'r we eould take hexaeUornaphthalene and In collaboration with the Monsanto remove 1 per cent of some unknown constit Chemical Company ire bare a much more i uent with which we are not now familiar comprehensive program in view to carry on. i* and eliminate the toxicity, that would be Therefore we went to continue that same a lovely solution. Whether we will ever be type of cooperation. *5 able to attain that I don't know. That ia There is one thing that I want to bring up .A one of the things we have in mind. in that connection, which wilt have to be -i As I said before, that is one of the things observed by the state authorities, when they with which all manufacturers of these syn go out to make these inspections. That is thetic organic products are confronted at the necessity of not creating mob hysteria some stage, either in their laboratories or in on the part of the workmen in the plants commercial developments. It is largely a where these inspections are made. Mr. question of timing as to when you should do Hemperiy has run into some very interest the work, how mueh you should do, and ing situations in the various examinations a whether you know how to do it. You have be has made. I know that he wouid be glad *:y to learn that first. to relate them and give the benefit of his experience to the heads of any of these etate Da. CxcuK. Danma: Dales* there is some other important matter I will declare the meeting adjourned. departments who will have the direction of this work. Otherwise I can see when we will be untble to get the full cooperation of not only the individual workmen but the Sr a plant foremen and the management, and we Da. R. R. Sanaa: May I say a word must have that if we are to get the results mote with regard to what Dr. Hookey stated that we art shooting for ever the next sev up os syphilis? If you are going to eliminate eral months or years. This thing may con *r all your workers who happen to develop tinue, probably will continue for yean. le .nj .*Ui i' i i ! GBRNQO1963 i W TOWOLDMONOOOI528