Document 4JJNpNZOYjBdQ7qY2pVX06pqV

SYMPOSIUM ON CERTAIN CHLORINATED HYDROCARBONS Harvard School or Public Health, Boston, Mass. June 30, 1937 Program 1. The problem of possible systemic effects from certain chlorinated hydro carbons. Cecil K. DarNtra, Madeleine Fitlo Waexes aj Gm-wole A Bex.nt.tt-' D<p*rm*at vj PkyriJ.Bmtri irAW o; hrUf Bulib i Dtp&tmrni tf Piikolegy, Btrm*4 Ue4u*l Schvd, *. if w. 2. Demonstration of laboratory method' for ventilating. perations emsloving chlorinated hydrocarbons A rtiscusssioc of permissible ronccntrslions of such compounds in the air. C. P. Vxclov, M.M.E. Autnm pF^nir tf By,rwM, flamrd S'imml fa'.V ffuM A VO Pbiui> UaisEta. Ch.E. ryaM tf Imtmuioi Ry:Um, E r--ini Sr-ovl ./ J't.iiie Et tit* "3`. A description of the lesions found in the liver of animals subjected to various chorinated hydrocarbons. GaANvatr. A. Bennett, M.D. tltftia* im rA-nSo, Barctrt Sirtini tckt-tl (The sacond and third (wpen will appear elsewhere. Copies of them will be sent to all who attended the tympcsuznj GBRNO01933 LEXOLDMONOOI804 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. Cxcn. K. DawxEa, Madtuot Field Waius asi GaAmnux A. Bliojett Dtttrtmal tf rkytitbtj, Btrttri Srkul/ fwiUe BuiI* tmd Dttmtmtt tf hlkt/fy. fmri lMfaaf ScW, Buts. Jtut. 2. Demonstration of laboratory methods for ventilating operations employing chlorinated hydrocarbons. A discusasion of permissible concentrations of such compounds in the air. C. P. Yaclou, M-M.E. A inilnl frtfttttr tf /WmjSmJ Dytitmt, Bimrt Stktti tf FwHk Hmtik PmuF Direes, Ch.E. ' rwjftmr tf Imlmthitl Bygitm, SwA Sekttl tf BmtUt BmUk 3. A description of the lesions found in the liver of animats subjected to . various chorinated hydrocarbons. Gsakvius A. Bissrt, MJD. AjmiiA is Frttalny, Btrttrt ITtlictl Srkttl (The second and third papers will appear ebewhm. Copies af thn will be seat to all who attended the symposium.) GBRN00193U LEXOLDMONOOI805 THE PROBLEM OF POSSIBLE SYSTEMIC EFFECTS FROM CERTAIN CHLORINATED HYDROCARBONS* Cecil K. Drinexe, Madeleine Field Warben and Granville A. Bennett Department of Physiology, Harvard .School of Public Health and Department of Pathology, Harvard Medical School, Boston, Mata. HE use of chlorinated naphtha rapidly and thoroughly as possible.t Tlenes end compounds of allied pharmacological possibilities is In brief these cases were as follows: Patient l. 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 ye&rs it has been known that many of these compound* 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 somewhat anemic and his skin, particularly with chloracne but with the possibility of systemic effects following ingestion or inhalation of such products. In the upon theanns, faee, chest and back, showed many pustules. He died ofter s 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 * Raeeivod far publication Jim* 10,1937. t The Halowax Company makes many products besides chlorinated naphthalenes, and it has eome to our knowledge that all of these products ore indiscriminately called "holowaxes" by purchasers and users, and are lumped together as possible causers of acne and even of systemic disease Since "halowax" is merely a trade designation, care should be token to describe compounds by their ehemical names and thus avoid condemnations which are both troublesome and misleading. GBRNOO1935 LEXOLDMONOOI806 284 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY ISept. itST have a cirrhosis of ths lira with scute yel low atrophy sapcrimpo--d upon it. Thii oil had been exposed to low concentrations of vapor* arising from a mixture of tetra who had been exposed to trichlornaphthalene. Of these 13 were found to have mild digestive complaints, and pentaehlornsphthalenes, together with anorexia, nausea and vertigo, but approximately 10 per cent of a refined chlo Courtois-Suffit remarks finally, "Ab rinated diphenyl. While both he and other* sorption is certainly posable and we engaged in the same work had chloracne, there were no other disturbance* of health have for proof of it some of the diges in fellow workmen, nor waa there any pre- tive and general complaints which ' eipitating cause for the acute yellow atro- have been due to it. But they appear . : phy such aa treatment with arsphenamine to be of little consequence considering . or exposure to dangerous concentrations of the mildness of the digestive troubles carbon tetrachloride. Patient t. This waa a young man who and the absence of respiratory phe . died in February, 193S, after aa acute illness nomena." i characterised by jaundice. He bad been In Touraine's cases the exposure was exposed to fumes arising from a mixture of to a trichlomapbthalcne, whereas the penta. and hexachlornaphthalenes. There i* no record of chloracne. The patient worked with a large number of other people of whom but one (Patient 3), a close friend, American cases of acute yellow atrophy were exposed to compounds of higher chlorination. Our own experiments had significant illness. indicate that trichlomaphthalcnes re Patients. Another young man employed quire enormous dosage, far beyond 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 anything encountered in industry, in order to produce liver damage. Teleky (1927) reported a number of cases liver Here again no history could be ob of chloracnc in persons exposed to tained aa to a precipitating cause, and there chlorinated naphthalenes with a chlo was no record of preceding attacks of rine content ranging from 14 to 53 per jaundice. 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 lemons 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 aa follows: 6BRN001936 T LEXOLDMONOOI807 i i |S&.IHT , trichlorvcre found mplaints, :igo, but .lly, "Abi' and we rhe digea rs which ry appear unsidering e 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 chlow 53 per ower the he acne. - number uichlor;anber erf . nothing -*e. Reentation, :hat aniienes re nd that, in or by peculiar" d Jarvik etiona of J naphn oil to -ed were rot. It, no. 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 acute 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 will 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 appraling 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 r unaiiMj--Jgw.y1 i**r GBRN001937 LEXOLDMONOOI808 286 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [StpL MT 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 axe 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 Experiments Animals.--White rats have been employed throughout. They permit the use of a large number of animals in a relatively small inhalation installa 22' x 22' x 14', in two tiers of five cages each. When the experiment was not in progress the doors were opened wide and the cages kept in place (figure 1). At the center of one end of each box --the inflow end--air was introduced .through a pipe 7 inches in diameter (figure 2), Each box was equipped with an individual variable-speed efeotric blower which blew the air through several feet of 7-inch pipe before enter rof. ii ing t mete' thefi could from deflw pipe sure strcai At outdo was t fitted a larg Alx the 7of thduccd ciallv (fipin dianif hold t were r that t top of this fi length 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 m. s ,i 111. j .ip BBRNOO1930 LEXOLDMONOOI809 tfST i very these .,-siblc tiiiuit. -.ri<tic8 .1 make - both ..ilation ;:i four each size t> f I n. i five '>t was ; ftied place li box luccd meter ;,Ppcd I elecMuigh nter red. 1, no. rj EFFECTS OF CHLORINATED HYDROCARBONS 287 iug 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 a as 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 pvrex glass flasks (figure 4), 7} inches long and with a diameter of li 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 tithe 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 electric 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 evert- 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 st the beginning of the run and at the end, and the loss in weight used to calculate the average I I I f t i i GBRNOO1939 LEXOLDMONOOI810 288 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY (&p<. lSt flowmeter readings. The figures ob tained were not absolute because of slight variations in the air flowing through the boxes and because of deposition of material on the ther mometers and on the inside surfaces of the box, but they checked well with direct determinations through air samples. Approximately 1 hour was allowed for the wax in the flasks to melt and come to a constant temperature. At that time the box doors were tightly closed, air bubbled through the flasks, and the blowers turned on. This was the beginning of the exposure period. By means of rheostats on the fans and dampers in the outflow pipes, the amount of air flowing through the boxes was adjusted and an attempt was made to keep the four boxes as uniform as possible--usually between 163 and 173 c.f.m. In the first group of experiments the following substances were tested: 1. A mixture of trichlornaplithalenes plus a trace of tetrachlornapthalene. Chlorine content 49.9 per cent. 2. A mixture of penta and hoxachloniaphthaleues. Chlorine content 62.6 per cent. 3. A mixture of 90 per cent penta and hexachlomaphthalenes plus 10 per cent 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 t Dog eggs, T1 begu expo chloi 16th com; ; 18th ! live i sure l kille . 15th Cox: Trie tc I Pent i 80S tec Chi per the gro exp for 1 16 Ea> cea 4:( we for ehi 6BRN001940 LEXOLDMONOOIR11 tar ob of illR -r of her* - of tith air ned and At inly --k, was riod. and the the aipt as reen -the iha.ilor.vent rine "nta "nes >riam- 'rine rcprinanrial ' ani seed urina tel. 19, no. 7) EFFECTS OF CHLORINATED HYDROCARBONS 289 Dog Chow supplemented by lettuce, eggs, milk and cod liver oil. This first group of experiments was begun on July 1, 1936 and the last exposure to number 2 (penta and bexachlomaphthalenes) 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 somewhat 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 TABLE 1 Condition's Maintained in Inhalation ExrxHiurNT rsoic Jolt 1 to Kovemses 18 and 18 UATBlUi> CBLO- HXI cemn fSHF. at, coBCunmnoi or Aim u mz mu. SS* rant AT. iaat kx* mm Trichloroaphthalenes plus traces of tetraehlornaphthaiene................... % 49.9 c. n. 150-180 1.21 ro|i High 2.60 Low 0.10 w. 1896 loin 16 Penta and hexaehlornaphthalenes.... 82.8 160-170 1.16 High 2.19 1854 Low 0.51 16 90% penta and hexaehlomaphtha* lenes plus 10% chlorinated diphenyl. 6S.0 165-175 1.27 HighS. 17 Low 0.64 1896 16 . Chlorinated diphenyl......................... 65.0 165-175 0.57 High 1.19 1896 16 Low 0.23 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 rats 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. The concentration ofchlorinated naph thalene* and chlorinated diphenyl in (As air of workroom*.--Table 1 shows that animals have been exposed to varied concentrations of the substances under BBRN0019H1 LEXOLDMON001812 290 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [SsjX. ItST test. The concentrations employed may be regarded as fairly representa tive of industrial experience. Prior to the initiation of inhalation experi ments a number of estimates of chlo rinated hydrocarbons in the air of dif ferent factories were made and the 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 wvtinm carbonate containing a trace of sodium sulfite. The beads are then washed down and the chloride deter eoncentratbns chosen for inhalation experiments depended on these exami nations. The technic of analysis and the apparatus employed were 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 col. it, no. 7] somewhat Tebbens's but devices are th in both cn=-. rinated hydro', acid and su:. l* sodium carbon f In our cafe cl I apt to be ve r; t less than 1 me t quently the at ( actually forme, so small that i' either graviiut t For this rcasot. use the nepheb I is sensitive to as 0.1 mgm. pc It is doubt; should exceed conversion ot pound to l:y- subsequent ab.- unlesa the velo low. .Another is that the me any cblorina: determined, distinguish he' gases but deter the results m II! puted in term At the pre? formation a< rinated napht! different pla;*'- instances the n repeated seve ! the amounts 1 i those used b # must be remc I The combc.ratus suited ta : by Willson Pr-. The equipmeat suction pump wi BBRNOO19M2. LEXOLDMONOOI813 al f*'i *! wd. U, no. f) EFFECTS OF CHLORINATED HYDROCARBONS 281 somewhat 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 quentity, intense for e short time and acid 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 procedure 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. seuversion of the chlorinated com pound to hydrochloric arid and its Rmuili of Inhalation Experiment*. subsequent absorption are not efficient 1. Animals exposed to a mixture unless the velocity of the gas stream is of trichlornaphthalenes plus small low. Another precaution to be noted amounts of tetrachlornapthalene. is that the method u 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 possess in never more than slight. formation as to the amounts of chlo 2. Animals exposed to e mixture of rinated naphthalenes in the air of 30 penta and hexachlornaphthalenes. different plants, and in a number of No abnormalities wen observed in the instances the measurements have been living animals. Rata were killed and repeated several times. Frequently autopeied every 6 weeks. In the first the amounts have been greater than animals sacrificed liver changes were those used in our experiments, but it observed. These were swelling of anst be remembered that the rats cells, alight granulation and hyahnixa- * Tbs combustion and absorption *pp ' tion. In September and October these rates suited to Sold sampling is new made conditions were somewhat more ad by Willson Products, Ins., wonting, Pa. vanced, end in November the process Tat equipment ineledaa flowmeter section pump with a carrying csss. aad , I became stationary. There were highly s i i * GBRNOO19M3 LEXOLDMON001814 392 JOURNAL OP INDUSTRIAL HYGIENE AND TOXICOLOGY IStft. 1M7 granular cells, hyaline inclusions and exposed to these compounds without mitotic figures, but no more *>" 2 illness of any sort. months previously. 3. Animals exposed to a mixture of The functioned appraisal of the liver 60 per cent penta and hexachlor- damage caused by certain Marinated naphthalenes plus 10 per cent refined naphthalenes and by chlorinated di chlorinated diphenyl No abnormali phenyl--There are no tests of liver ties were seen in the living animals. function useful in such minor degrees After 6 weeks the livers showed of liver damage as were produced in changes similar to those in the animals these experiments. Indeed the ani exposed to penta and hexachlornaph- mals resisted 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 firtl 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 ""' They equal degrees of exposure. It was our held their weight, ate and behaved idea that perhaps many of thaes 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 t i i ! i i i 1 l I i i i i toL It, any m nation such e disturt not a which this r over t Knc had 1 slight we dc substf struct alcohc matio chlori per k: norm.to 0.' 0.73 < Tli tube Rials folloT Rale . 1. 7 Man 10. K 2. at 9:: 3 1 1 1 1 3. thole Fed 6BRN00l9im LEXOLDMONOOI815 aaL it, na. 7) EFFECTS OF CHLORINATED HYDROCARBONS 293 any means other then autopsy exami nation. If, upon the substratum of such changes, they got an acute liver disturbance, acute catarrhal jaundice, not a very common disease but one which any of us may experience, would this relatively innocuous disease go over to acute yellow atrophy? Knowing that our inhalation rats had liver changes, but changes too slight to cause recognizable symptoms, we decided to test their resistance to substances known to cause liver de struction. Carbon tetrachloride and alcohol were selected. Having infor mation that 1.0 cc. of carbon tetra chloride plus 1.0 cc. of ethyl alcohol per kilogram would kill 14 per cent of normal white rats, we reduced the dose to 0.75 cc. carbon tetrachloride and 0.75 cc. of ethyl alcohol This mixture was given by stomach tube to the following groups of ani mals and with the results found in the following tabulation. Rail Jtd O.lf cc. far bym. weft / carbon Utrochlorid* and ethyl alcohol by tiomack tuba ' 1. TriMornaphthalen* pint traea of Utrnehlomaphthalena. Fed it 9:00 *~m., Nov. 10,1938. 10 rats. No deaths. 2. Penta and kcxachlornapktkaUna*. Tad at 9:30 a.m., Nov. 10,1935. 10 rata. 9 died Nov. 11th between 4:90 and 10:30 p.m. 1 died Nov. 12th at 3:20 pa. 1 died Nov. 12th at 4:90 paa. 1 died Nov. 13th between 9:30 and U:30 ta. 1 died Nov. 15th between night of Nov. 14th and 12:30 p.m. Nov. 15th. 3 died Nov. 19th between 10:15 pjn. Nov. 16th and 9:00 an. Nov. 10th (stiff). A 10 par cant panic and hcxocklornaphtbaJene* and 10 par ctnl eUorinolad diphenyl. Fed at 10:00 a.m., Nov. 10,1909. 10 rate. 1 died Nov. 10th between 5:00 and 10:30 p.m. 5 died Nov. 11th between 4:90 and 10:30 pm. 1 died Nov. Uth between 4:30 p.m. and 9:00 e.m. Nov. Uth. 2 died Nov. Uth about 1:00 a.m. 1 died Nov. 13th between 5:00 and 10:00 p.m. 4. Chlorinated diphenyl. Fed at 10:00 a-m., Nov. 10,1939. 10 rate. 1 killed Nov. 10th at 10:30 p.m. (almost dead). 2 died Nov. Uth between 4:30 and 10:30 p.m. 1 died Nov. 12th before 5:30 a.m. (itiff). 1 died Nov. 13th between 9:30 and 11:00 a.m. 1 died Nov. 19th between 10:15 p.m. Nov. 16th and 9:00 ajn. Nov. 16th (itiff). Control*: Fed at 9:30 a.m., Nov. 12,1939. 10 rata. 1 killed Nov. 13th for normal liver. This tabulation summarises into the facts that: - 1. No norms] rats were killed by carbon tetrachloride and ethyl alcohol. 2. No trichlomaphthalene exposed rats wen killed, and this finding agrees with our inability to find lesions of moment in the liven of the animals that inhaled this substance. 3. The penta and bexachlorinated naphthalene, the mixture of these with 10 per cent chlorinated diphenyl, and finally the latter substance alone seem to have produced conditions lowering the resistance to an agent capable of producing serious liver disease. 4. The sole lesion produced by this test of liver function was acute yellow atrophy usually accompanied by jaundice. 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. 294 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [Sep*. JM7 In animals with the minor degree of liver injury which has been described we were unable to produce acute yellow atrophy or any variety of liver effect with arsphenamine, cincophen, butyl chloride, ethylene chloride and tetra* ehlorethylene, but carbon tetraehlo* ride was uniformly effective in disclosing the existence of liver damage, Recovery from fieer damage following removal from exposure.--Animals exposed to trichlomaphthalenes plus traces of tetrschlornaphthalene being practically normal on removal from exposure need no'consideration. In the case of the penta and hexachior- sign* of liver injury will be many months in returning to normal. The effect of high concentrations of trichlomaphihalenet with iracet of tetraehlomapkthalene.--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 the inhalation boxes was arranged TABLE 3 Cokditios* Maintaixxd tnum Ixiiutio* or Hioa CowemmLiTiom or TlICBXOlLVArHTSAlXKt* FLU* TrTSACBLOKXArBTKAUSK mi--ii -- ay,acrniBcBWmieusnM EZTOOQTBAOLIS AT. MAT SSBOOOM c. m. TON* Umt W Trichlornaphthalenaa plus trace* of 137-300 10.07 High 16.49 tet racMornapbthalene Low 5.78 1233 16 . ; j : j 1 ; ! j j naphthalene, rats 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 of the mixture of penta and hexachlorinated ^naphthalenes and chlorinated diphenyl and for chlorinated diphenyl alone. Apparently the changes induced in the liver cells by these substances are exceedingly persistent and one must expect that an individual showing any so that fumes from four glass contain ers were delivered to the air line instead of one. This resulted in the conditions shown in table 2. The animals 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 liven showed massive central necrosis and j j : . . ; . ; . ; *. in 0 rats one chle toxi the) UP trat ^ The *KC but Prt cou* ntl Coxi Pent. atro; use On subj mar was the and sure then for kii!e< and expo kille* fattj with anim ^"ui..hwiii , sieL'i GBRNOO 19*46 1 >. . LEXOLDMONOOI817 wt. l, no. 7] EFFECTS OF CHLOREv'ATED 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 effect* of high concentration* of penta and hexachlomaphthalene*.-- 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 effect* of penta and hezachlornaphthalenes, the mixture of theee with 10 per cent chlorinated diphenyl, and of chlorinated diphenyl alone, when inhaled in low concentration* through an 8-hour day indead of a 16-hour day a* in the firet 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 CONDITIONS IhintLVtD DURING Is'UUTlOM OP HlO> CoNCBWnUTiOXS OP PlJfTA AND HsXACKLOaNAPUTSALEXXS ' VATBIIU a*. ctKecraunos WAiaortex TOTAL *T. MAT E0BWU c. . Penta and hexsehloraaphthalenes........ 137-195 1.88 ffttfl High 14.0 Low 5.75 Inrt 608 Inri 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 eon- 296 JOURNAL OP INDUSTRIAL HYGIENE AND TOXICOLOGY tSepi. MJ7 eentrations of these compounds such ss 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 erperimentt. The findings that have been described briefly will be amplified upon the pathological ride in a further paper by Dr. G. A. Bennett. What has been given is, however, sufficient to indi men never inhale enough of any of these substances to get acute 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 Coksitioxs Maixtjjxxb ocaixo ImuuTiox or Low CoxcswraiTioNs or Three CoxroTOos dcxixo g-Hooa Ixsteao or 18-Hotm Periods lumuh -- AT.COMCttmiWI or AIM 0 BOX totAJ. A. MILT KXTOOriX izpooru c. M#7CTk Pent* and hexachlornaphthalenee......... 149-188 1.44 80% peata and hexachlornaphthalenee plus 10% chlorinated diphenyl.......... 150-187 1.86 Chlorinated diphenyl............................. 158-174 0.83 High 2.58 low 0.42 High 3.30 Low 0.50 High 3.23 Low 0.03 Inn 820 812 820 IrttM 8 8 8 cate that compounds more highly chlorinated than trichloxnaphthalene 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 tins 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 which the 10 animals in a cage had an equal chance, the amount of the compounds added being reduced as the number of rats lessened during the feeding period. The experiments were designed to 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 at damage. The experiments were successful in both respects, and indeed one may anticipate that future appraisals of the possible toxicity of chlorinated hydro- to!, ti carbt feedi rate sary esscr in tfc by b< diffe seem so ft ever T, tetra on unti ning to t and thre an in whir loss was* deat spin tion H slig' of g 2 Fee do;All we i 29, A logi affe tag, siot the wa: l Fee dos GBRN001948 LEXOLDMONOOI819 ItST ny of rellow rquire upon -,y de,er of is to comUhing made 1 were mixed .on for :ntxs .T, SUIT s 8 8 placed . the 10 chance, ; added of rats period. - to pve icity of loxicity the site ?sful in ne may .1.' of the i hydro Ml. it, mo. T) 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 penia and hezachlor- ever way they are administered. naphthalenes and 10 per cent chlorinated Trichlomaphtkalene plus traces of diphenyl.--Feeding began May 4, teirachlomaphthalcne.--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 Tetra and penlachlomaphthalenes.-- 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 by 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 rata 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 Praia and hexachlomaphthalenes.-- remaining were sacrificed. Those rats Feeding began May 4, 1936, a 3 gm. that died showed losses in weight, dosage bung used. By June 6, nine while those sacrificed had recovered l I \ ii i i i i t i i i8 r i i i ii i i I i i I t l l 'J 11 IM I GBRN001949 ***' '' LEXOLDMONOOI820 298 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY |5<?l. IM7 their initial loss in weight and wen gaining. The liver lesions were similar to those found in rats fed penta and hexachlomaphthalenes plus 10 per cent chlorinated diphenyl but not so marked. Summary of gnu feeding experi ments.--Of the various materials fed rats in large doses trichlornapbthalene plus traces of tetrachlonaphthalene 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 hexachlomaph thalenes increased the toxicity. Chlo rinated diphenyl alone produced liver lesions but in the dosage used was less "effective than when mned 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 rate and rabbite received this doee each day. The compounds used were those employed in the gram feeding experiments and the results were essentially similar though the lesions were lees severe. Subcutaneous Injection* The mine gum acada suspensions were injected subcutaneously into rata and rabbits, the dosage being ealeulated on the basis of 4 mgm. per cu. m. of air. Again similar results were obtained. In ail 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 Eeems to determine the systemic toxicity, and it is a striking thing that when trichlomaphthalene is reached systemic effects are never marked -and are produced with the greatest difficulty. It is 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 livers of ani mals very severely poisoned by penta and hexachlornaphtbalenes but have found no increase over normal figures, though the liven, as determined histo logically, were very severely affected. At the present time we are conducting inhalation experiments on a chlorin ated diphenyl containing 55 per eent of ehlorime instead of 64 per cent as in the esse of the experiments reported in this paper and on s compound with a chlorine content between tri and tetrachloroaphthalene. We are also determining the degree to which the (bet may increase or decrease toxicity, this being suggested by amfiar work upon carbon tetrachloride. In the baas of theee experiments rol. 1$, and oi differ* rooms tsinly that t more of th napht compt are many plant; been 20 ye fact been huma Time chan{ but t safe. m rar< hydrt safeg lead Coc* F t ( t r t 6BRN001950 LEXOLDMONOOI821 :?S7 iCU- . m. .ore TitS ees .bly .ted `dy -.t'.ht -ftS and rase rree . the :ing :eis rver the irktnds iiver .aths rally ' anionta cave -'ires, . isto.cted. :cting orin cent at as xrted : with i and ; also h the ::ieity, work went* of. It, mo. 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 an 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 CorxTOts-ScmT: Etude *ur riatoxieation professionnelle par Is trichloronaphtaline. Ann. de mid. 14ga)e, 14, 423 (1934). Abstr. of paper by Tocbact, A., ax MfotTBXL, B.: Dermatoses profesaionnellea par la aapbtaline et sea derivda. Prat. mtd. fraof., It, 335 (1934). Fumr, F. B., aim Jams, X. E.: Aetion of eertain chlorinated naphthalenes on the liver. Pros. Soe. Ezper. BioL A Med., U, 118 (1936). Lnunr, K. B.: Eursss Lehrbueh der Arbeita- and Geverbehypens. 8. Hir- sol, Leipzig, 1919 (p. 251). MimuTiPT, O.: Gewerbeschfidigungen dureh Haftax (Trichlornaphthalin). Inaug. dissert., Jena, 1935. Tzassxs, B. D.: Portable combustion ap paratus for field determinations of chlorinated hydrocarbons. Txis J., It, 201 (1937). Txuxt, L.: Die Pernakrankheit (Chloraeae). Klin. Wehnaehr., 6, 897 (1927). Tounanm, A., 8oLKrra, Mixtnni., B., asm Auabum: Cinquante-quatre eaa de dermatites par trichloronaphtaline. Bull. Soe. donnat. at syph., 41, 265 (1934). i i wjs.au1 if1 GBRNOO1951 LEXOLDMONOOI822 300 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [Stfl. J$S7 Discussion Dm. Cxcn, X. Dawns: Vi havm bad quite a long morning, but sine* Dr. Tea Oettinges baa to leave, I am going to aak bim to say a word. Dm. W. F. ton Omuroxx (Director, Haskell Laboratory of Industrial Toxicol ogy, Wilmington, Delaware): I wiah to con gratulate Dr. Drinker and his group on the very interesting and excellent work on the subject. I also wish to congratulate the Hslowax 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 toxicity and especially with the mechanism of the action. 6inee there is no animal which corresponds in all its physio logical characteristics to the human being it is important that such compounds be studied with different species of animals so that one can get a eross-eeetion 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 sre individuals who are apparently more susceptible to certain toxic agents than others. On the other hand, we have to try to detect the very first signs of incipient poisoning in order to prevent more serious damage. In the present instance it is very difficult to find 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 which will allow the physician to determine incipient damage of the organ before serious clinical symptoms become manifest. Thank you. i/lasMsJmhe Da. Caen. K. Duran: 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 aak Dr. Sayers if he will open the discussion for us. Da. R. R. Sstxbs (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 with toxic 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 can use them and use 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 is used. I have information from one or two of the other men who are in the audience that in plants where damage 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 control. After all, the proof of the podding 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. Neither profession alone can be successful. We have got to work together whether we like it or not. I hap pen to like it. There is one other thing. Aafaraemat^ rials are eoneemed I think we ought to be '. i "Wva V *ol. IS, a. !I eesmssafurtllye.nt ! adapted f I it. Anotl i vious to 11 was flamn approxima say appro never just Itmight h were quite happened t with this n electric cal I aanrdmtovrssonbct-hi. I proximetcly to a steel it bottom of th inspection it bide cap-lam the fire kiilct mine. Mirny Here >< L Now we have due to the t evaluate then I era inform* not just xuio flammability chlorination i> alao increases creases, acor> think that ch* have these has control them, we can. . Perhaps wetare better ever, present time I t better. I arn asubmarines, it i Don-CainmaMe s of their electrics Da. Cecil K.: you cars to cay a Da. ALater r of Oeeupaticaa: necthut Departs Conn./: Dr. L;-.anythitg that I this materia: it ' l I 6BRN001952 LEXOLDMONOOI823 Stpuinr -'vision of : stituta of ire, Washidies tad .1 of pleat* ;en to the -lion and . .inf. Dr. ember* id discussed the mano- -k but not d on here. ..x seems to er hai ear* part* of it .^d. iinces, but inee* each -mful subThat theae no matter them and Drinker : fact that ^nd can be nalowax is one or two _e audience = been done ver damate ' -.ufacturcre ui* and ap'cring eon* ~t medical riding ia in cetthedia successful, matter what ngineering, Ve must go isiou alone m>t to work uot. 1 hap -- /sr as mateought to be as*. It, as. t] EFFECTS OF CHLORINATED HYDROCARBONS 301 nart enough to use every one of them sue* number of ao-cailed cases. AO I can say is eeaefully. If this material is particularly a confession of ignorance on our part at that adapted for a certain purpose we should us* time and I was very glad to tee that your it. Another material that was used pre digging into the literature as thoroughly as vious to this for insulation purposes, which you have hasn't elicited any further infor was flammable, caused a disaster in which mation than ws were able to get, basically. approximately 167 men lost their lives. 1 About all we eould find was about the two say approximately 1S7 because they were eats that our friend, Lehmann, experi never just sure whether it was 1ST or 1(8. mented with. We got in touch with him and It might have been one or two mors but they he confessed that the amount that he had were quite sure that 1S7 lost their lives. It given the eats and his method of determin happened when they had insulated a cable ing it were probably subject to very serious with this material. They had an armored scientific criticism, and we agreed with him aleetrie cable. It was covered with lead on that point. armor on the outside. It was 1200 feet long W* felt, and I am very glad that it is what and was being lowered into a mine shaft ap you feel a* a result of your experiments, proximately 3000 feet deep. It was lashed that if we put in an efficient ventilation sys to a steel rope. It slipped and fell to the tem sufficient to prevent the dermatitis, we bottom of the shaft. When the foreman was probably wouldn't have liver damage. inspecting it he set it on fir* with his car That is what we did entirely empirically. bide cap-lamp. The carbon monoxide from I think that is about all I have to say. I the fire killed those men that were in that have been delighted to be here and to have mine. Many of course escaped. as many members of my staff here as I eould Here we have one hazard, a fir* hazard. jaek out of the office. We have been de Now we have another one, a health hssard lighted to listen to the discussion. due to the toxic materials. W* have to evaluate them. Certain of these materials, Dm. Cscti. K. Daraxcm: May we now I am informed, ar* also flammable. I am make the discussion general and those who not-just sure how flammable they ar* but have questions please volunteer. flammability probably decreases as your chlorination increase*. But your toxicity Mm. Mi-vran Bownrrcm (Director, also increases as your chlorination in Division of Occupational Hygiene, Massa creases, according to Dr. Drinker, and I chusetts Department of Labor and Indus think that cheeks with other findings. We tries, Boston, Mass.): I would like to second have these hasards to balance but w* can very strongly what Dr. Sayers has said with eontrot them. I feel quit* confident that regard to the approach to this problem in w* can. ' proper control rather than by prohibition, Perhaps w* can find other substances that whieh seems to me wholly unnecessary not ar* better even than this material. At the only in this case but in the case of other present time I am advised that w* have no toxie substance* withwhich we have to deal. better. I am advised that in ship*, each as The problem of proper ventilation seems to submarines, it is quite important to have a me relatively simple from what I have heard non-flammable substance for the insulation of the situation thus far. The problem of of their electrical wire. maintaining that ventilation properly does not seem to me quite so simple. I think it Dm. Caen,K. Damn: Dr. Gray, would is going to be quits necessary that there you can to say a wordT should be a very adequate inspection of the plants using the materials and I can Dm. Albuut 8. Omav (Director, Bureau assure you that that will be thecas* here in of Occupational Diseases, State, of Con Massachusetts. necticut Department of Health, Hartford, When this trouble first broke ia this state Conn.): Dr. Drinker, I don't think there is a little over a year ago we issued a quite anything that I can say except that w* ussd strongly worded warning letter to all plants this material ia Connecticut and w* had a using these substaness and it has all along i l t I if I .<. ppypi i iua,i.i mj^at isi . i ii i * nn l *u m s-! ; '. it* w 6BRN001953 LEXOLDMONOOI824 ,-fcWi I 30? JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY IStpt. JUT been my pita to follow that op with fur ther letter bringing the eituition as we bow know it, >e a result of Dr. Drinker's work, to the attention of user* in this state. In that letter we shall unquestionably advoeate the concentrations that Dr. Drinkar has suggested this morning. One point that I think is worth comment ing on in that connection is the question of identification of the substances. It is ex tremely important from the state adminis trative point of view that employers using these substances should know what they are using. They are identified at present only by numbers. If we list those numbers in a warning letter which a-e send out there are likely to be changes in those numbers. The Halowax Corporation ia a progressive con cern and it it 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. SxxnroBB Bnowx (President, Halowax Corporation, New York, X. Y.); There are some aspects of this situation on which I think I can enlighten the medical and state and civic authorities, with respect to the commercial and practical aspects. If you go into the research laboratories of any large 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 as the chemical manu facturer is concerned ia a question of timing. You have heard this excellent presentation given this morning by the Drinker brothers as to tbe work that they have done here. Should you take a product of which you have developed, say, 6 or 10 gm. and spend IShOOO on 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 an producing only one hundred substances a year you can see that would run into boxcar numbers In the way of dollars and cents before you ever sold any. That is the problem we have bed in this case. It has been on the market for 25 years. Until within tbe past 4 or 5 years there has never been any intimation that it would cause any systemic effects. Thou sands and thousands of workmen have dealt with millions and millions of pounds of cer tain of these materials, particularly the trichlomaphthaleaes. Then we come to the higher stages, combined with chlorinated diphenyl and other products, and suddenly this problem is presented to us. We had asked various authorities in terested in public health, going back over a period of 15 to 20 years, to investigate it but there wasn't much enthusiasm for it. Mr. Bowditch suggested that we take it up with the Drinker brothers at this institu tion, which we did. You know the results of that wrork. Now so far as these changes are con cerned, they are beyond our control to a certain extent. We will manufacture a product--let's call it 1231. It has certain chemical sod physical characteristics. It is supplied to a cable manufacturer. It ia composed of certain constituent*. There may be some tctraehlornaphthalene, tri- ehlornaphthalene, paraffin, a little pitch or bitumen, and possibly tome chlorinated diphenyl. It does a certain job but he wants it to a little more plastic or he wants its viscosity or the specific gravity changed. Pcaaibly by a change in those constituents of only 1 per cent we can get that particular property. We can't sell it to him as the same product so 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 cornea to a question of cooperat ing with the state authorities in that con nection, if there were some major change scads fat a product we would have no hesi tancy in advising them and we would also advise 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 he physical or chemical. Those are some of the practical problems LEXOLDMONOOI825 Ml. U, no. 7] EFFECTS OF CHLORINATED HYDROCARBONS 808 with which all manufacturers of cbcaicali are confronted today, particularly la the synthetic organic field where the develop ment it ao rapid that our aalea departaeata can't eves 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 say 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 best 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 his 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 thst it was or was not connected with his work. Knowing the man as I did when he was employed, with the'superficial examina tion that he had, be appeared to me very thin, pallid in his appearance, and I would not say from my poor knowledge ot the physical make-up of the human being that he presented a healthy appearance. How ever, it was only for a 6 months* period from the time of his employment that ha com plained of this constipated condition and we advised that he see his home physician. It rapidly developed to the point when he was in the hospital and in a vary short time he died. More serious than that perhaps is the fact that we had 80 other man in very bad condi tion as tar as the acne was concerned. The first reaction that several of our executives had waa 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. Wo might just as wall have thrown our business to the fourwinds and said, "Well 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 wo did develop--and I was most closely associated with it--and set up a routine for bringing these men back to nor mal health conditions. A number of them were sent to Dr. John H. Stokes and to Dr. O. H. Perry Pepper of the University of Pennsylvania Hospital, and the others to Dr. Isaac R. Pels at Johns Hopkins. Through their recommendations and studies we employed a trained nurse and two local physicians and you might say established a small hospital and its facilities at the plant. Through the application of 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 18 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 appearanee as my own. I tell you we are very proud of the fact that they are still all em ployed and the amount of halowax that we are using today is even greater in quantity and in types than we were using a year and a half ago. With the adequate ventilation system we have installed, with the routine for change of clothing from street clothing to work' clothing when they come to work and the reverse of that process, with the assurance that a shower will be taken before the street elothing is again put oa, we have found ao 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 say 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 (ftpf. to w all ia industry u mm very funda mental work mi don* u humans, as Dr. Jones mentioned before we cam* into this meeting, some control in fundamental work to determine some method whereby we may determine the inception of any liver dis order. We have had our men examined ia groups three times sines the trouble developed and nothing has shown up in any one man. W* have learned and appreciate the fact thatwe must handle hazardous materials, but w* have learned bow to handle them. It has been a very great experience for us and for myself, and again the best teacher. Dm. Cecil K. Dxineer: Can you recol lect the air concentration that you are main taining now with your present ventilating equipment! bln. F. R. Ka.ikex: We have had two examinations made of tbe air by Mr. Wil liam F. Hemperly and they average from 0.2 to 0.6 mgm. per eu. m. We recently dis covered one condition which was found as the cause of a high reading in on* of the examinations. Tbe compound is one that ia not manufactured by the Halowax Cor poration that is used rather infrequently, perhaps not more than SO gallons of it in a 6 month period. Itit in tbe form of a paste, reducedjritb solvent to a past* 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 tbe cause of throwing the retulta off to a high value. It was then about S mgm. pereu.m.f I believe. That is going to be eliminated now. That is a combination of toluene and carbon tetrachloride solvent. When that compound is exposed to tbe air the chlorin ated solvent odor is completely masked by the toluene. Itis lost. I was able to detect it only by removing the head of the drum and immediately smelling the odor of carbon tetrachloride. Aa soon as that bead was removed for a period of 10 seconds the toluae predominated and we had no knowledge of the other being in there. kin. Annum G. Bam (Research Engi neer, United American Boeek Corporation, Springfield, Mass.): Do I understand you to eay that those men who were afflicted are back on the same job! ' Ma. F. R. Kansan: They all returned ta normal skin health, as I say, and are work ing on the same Job. Da. Caen, K. Daman: Dr. Schwarts, you have seen a good deal of this general subject. Da. Louts ScawAUT* (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 an ordinary acne vulgaris and kept away from further large exposure they all get well, with the same results as acne vulgaris. Those who have large pus tules may have scars resulting and those who have superficial pustules or only come dones won't have any scars. As far as prevention goes, I felt even be fore this investigation was undertaken that this substance, like any other poisonous substance, can be handled and used in in dustry provided proper safety precautions are taken, sad 1 so advocated at the meeting fat Pennsylvania when this was discussed. About ventilation and safety precau tions, I think that while w* cannot, with our present knowledge, detect by any chemieal tests the early symptoms of intoxication from this substance, the akin offers an easy way of proving whether your method of ventilation is efficient or not. If there are any eases of sen* or of this dermatitis occur ring in a plant whars halowax or the chlorin ated naphthalene or chlorinated diphenyls an used, then that shows that then ia suf ficient concentration of them substances ia the air to cause plugging of the follielee and to cause a alia condition. If these is sufieiant concentration to do that these may be i GBRN00195A f LEXOLDMONOOI827 afr a* a nsol. 19, no. EFFECTS OF CHLORINATED HYDROCARBONS 305 sufficient concentration to cause systemic poisoning in the It* people who ore hyper sensitive to the action of these hydrocar bons. Everybody is not hypersensitive to them. If they were, of the thousands of people who have been handling these sub stances, more would have contracted this disease and it would have been reported very much earlier. This material was used in Germany as early as 1914 or 1915. While I cannot add anything to the methods outlined here for safety in the wa/ 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 the substance in the air to cause acne and consequently sufficient perhaps to be dangerous to the few people who are hypersensitive to its action. Dn. Cscit K. Drctkeb: There is a prac tical point in regard to the question of deter mining these substances in air. My brother pointed out this morning that there are several pieces of apparatus for doing this. It has seemed desirable to a number of the men who are here that during the next cou ple of years, while we are in a position of learning, that we endeavor, if we can, to confine our analyses to one piece of appa ratus, so that at least our results will be as comparable as we can make them from place to place. I don't know much about this phase of the subject: perhspa, Mr. Cook, you have an idea or two about that. Mb. Wannsw A. Coox (Chief Industrial Hygienist, Bureau of Occupational Dis eases, State of Connecticut Department of Health, Hartford, Conn.). On the deter mination of the halowax I wonder if it wouldn't be preferable to have Mr. Hemperly discuss the method he has been using throughout the country for the determina tion of chlorinated naphthalenes. Dx. Caen, K. Daixxrs: I think so far as that is concerned it is best to leave that to discussions with Mr. Hcmpcrly 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. Mx. Vain A. Cook: I am not quits sure that I have in mind exactly what you want in that regard. In connection with amplingT Da. Caen K. Durum: Yea, In con nection with the whole technic of determin ing the material in air, length of sampling, type of apparatus, and so forth. It has keen suggested that we endeavor to agree upon some uniform procedure for that and as figures begin to come in, as they will in the eourse of the next couple of years, we will at least have them on a comparable basis. Mb. Wanner A. Cook: In that regard there is no question bnt what the determina tions and results of analyses of the concen tration of injurious materials in air, corre lated with pathological findings or freedom from pathological findinp, 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 organizations equipped to make determinations of injurious materials in air should do, is to make an effort todevelop 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 avenge daily exposure. There is a tendency very often in taking samples of air to determine maximum exposures, to get the exposure over a 15 or 30 minute period when the worker may be actually tending a pot where the material is being used, whereas during the subsequent half hour he may be 40 or 50 feet away from that particular location. Therefore, for one thing, it seems to me it would bo extremely desirable to obtain in formation in as many plants and as many loeatiooa as possible of the average exposura, taking into consideration not only the worker's maximum exposure white actually j i BBRN001957 LEXOLDMONOOI828 308 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [Stpi- tm f I 1 i at mk with them nutcrlilt but ibo Ua before the A. P. H. A. ia October as one of much amallcr exposure and possibly even the projects which we shall carry out at lack of czpoaure aa he may go to other parte -that time. of the room or even to other department* Aa I have not given this consideration, I during the eourea of the day. am afraid my discussion is not as connected Another type of determination which as I might wish it to be. We have a real seems to be extremely desirable to have ia problem bare and one that deserves some concentratione of the chlorinated naph study. thalenes at certain reference pointa. I believe that Mr. Hemperly very carefully Da. Cecil K. Dxixkex: Would it be of duplicated these reference points in each service to the American Public Health Asso- of the planta where he took hi* determina * elation Committee if a sub-committee from tions. He took the samples, I believe, at this meeting, collected perhaps by my breathing level and a certain measured dis brother and those of you involved with these tance from the pota where the chlorinated problems, were to make a recommendation naphthalenes were being handled, so. that to the A. P. H. A. as to the things you have ] next year he could go back to those same brought up and aa to suitable apparatus, locations or others could take determina and let the final statement come from the tions at those same locations, which are Association after they have considered that definitely fixed and recorded, and learn material? whether, due perhaps to dogged pipe lines or to fans which might become loaded with Mb. Wui A. Coox: I think that the condensed chlorinated naphthalene, would be a splendid idea because we have there might be poorer ventilation than origi a bulk of information on this particular nally designed and higher concentrations material. A number of individuals have of tite chlorinated naphthalene than origi given much thought to the development of nally determined. ' apparatus, both the combustion method It seems to me that it would be an ex whieh we have here and also the continuous tremely desirable thing to have made avail record type of apparatus which Professor able for all of us who are making these Drinker mentioned this morning. I think determinations these reference points so that it is a sufficiently important project that in Massachusetts and in Connecticut, that a subcommittee made up from this at one plant or at another, a considerable group could give that committee a very group of workers could be taking samples at definite steer. this one particular point with reference to [Personnel of the Sub-committee: W. A. the source of generation of the vapor. Such Cook, chairman, A. L. Coleman, H. B. El results would permit a comparison of knowl kins, W. B. Fulton, S. W. Gurney, E. R. edge between plants. Hayhurst, W. F. Hemperly, F. W. Sehl, and In that regard it happens that there is a A. N. Setteriind.) committee of the American Public Health Association which ia charged with the devel Mb. Hxbvst B. Euuxs (Chemist, Divi opment of chemical methods for determina sion of Occupational Hygiene, Massachu tion of atmospheric contamination such as setts State Department of Labor and Indus that now unto consideration. It seems to tries, Boston, Maas.): In connection with mo that it might bs a very desirable project what Dr. Schwarts has said, I am not sure for that committee to consult with the in that I am ia complete agreement as regards vestigator of the Halowax Corporation and the use of skin lesions aa warning slants. suggest to all of those who are doing work It is my understanding that ia insulated of this type, after some discussion, what wire planta the chlorinated diphenyls are reference pointa eould be adopted and also very commonly compounded with the chlo what should be dons in connection with get rinated naphthalenes. It ia also my under ting these average exposures. As a matter standing that these are more likely to cause of fact our committee will diaeusa that very a severe skin irritation than the straight feature and possibly include it ia our report chlorinated naphthalenes. On the other GBRN00195B ASMaUaSUMs LEXOLDMONOOI829 Ml. It, a*. 7] EFFECTS OF CHLORINATED HYDROCARBONS 307 hand, from Dr. Drinker** work one would Judge that the straight chlorinated naph thalene waa 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 yean, 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 chances 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 fat 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 chances 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 is kept as low as was recommended this morning, the chances of having toxic effects are very small. Ma. F-R* Kaiucs: 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 chloronaphthalencs. Did you mean by that, that the acne condi tion actually waa more pronounced with the compounds than with the straight ehloronapbtbalene 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 ehloronaphthalenes are leas harmful in so far aa acne is concerned or is it because of the handling of batch compounds? Dx. JonxA. 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 th* man in the plant said -'w.r -I --^ As 308 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [Stft. 1937 cU I that they developed eeoe more often end vulgaris is most apt to ooeur. Thtsubaeemete severely after they started making ous glands are moat aetiva and they seem to I tha tioi compound*. It may be that it was in the have it much more than the older people in coli method of the handling. whom the sebaceous glands art sot so I active. Dr. Mn. F. R. Kanina: You lay that the con Ws keep a dipping of all articles relating hav dition inereaiee with the inereaaed chlorine to industrial dermatitis in my office and 1 cur V content and we ate attributing the acne pri recently rend an article la a German maga- tbs marily to the chlorine radical. If that is sine in which they report in Germany a hot true, what are we to associate insofar as similar sene condition from chlorinated 1 these various other constituents are con phenols and chlorinated benzenes and solid exp cerned, such as various plasticising agents? waxes, ft seems that this acne-like condi cat ' How much do we know about those insofar tion is not peculiar to halowax or chlorin and at development of acne is concerned? Some ated naphthalenes or diphenyls but can left of these compounds have a half dozen con occur with any condition that blocks up the a h; stituents in them other than rhlorodipbenyl sebaceous follicles of the skin. pou and ehloronaphthalene. We are at the toe present time considering the chloronaph- Da. Rotax. Mxxxxm (Special Agent, be < thslene as the basic element responsible for State of Connecticut Department of Labor, pic: the acne condition which we have. We Hartford, Conn.): I am full of questions. Mr know very little about what the other mate As a statistician I am n little hit suspicious Coi rials may or may not do. of averages, so I should think that we should it. take maxima xs well as averages in getting saf< Da. Job* A. Hooext: I don't know at th* threshold dose or the dangerous im slur about these other materials. Perhaps Dr. pregnation of the atmosphere with these all < Schwarts would know something more poisonous compounds. 1 just wanted to ntc about them. drop that ss a hint for this committee to consider in it* work. cat: or * Dn. Locis ScaWASTi: It is well known In spit* of what you said at luncheon, und in industry that there are many compounds Dr. Drinker, I still think it is rather impor nti that cause acne. For instance, paraffin acne* .and oil senes have been known for a long time. Paraffin acncs, was acnes, are simply a mechanical plugging of the fol licles of the skin by the minute particles of wax that fall on the skin. I think that the acne caused by these chlorinated naph thalenes and diphenyls, because it is caused by both--I was down at the Swan Chemical Company where they make chlorinated di phenyls and they have acne there just the same asover at Wyandotte where they make the chlorinated naphthalenes--I believe that that is caused by the same thing, a blocking up of the follicles of tbs skin, the formation of the eomedont and than the eomedone becomes infected and forms a pustule. They don't all pustulate because they don't all become infected. Many of these men never have any pustules. They just hare little whits elevations on tbsir skin. In those people who are in the acne age, the youngsters of U, 10, 8 and 8, seas tant to determine how the plugging of the pons actually doe* occur, whether they an plugged as Dr. Schwarts ha* suggested, from th* particle* falling on the outside of the skin or whether they an plugged, as so many doctors have informed me, from inside aa it wan. Th* fumes an breathed, the substance gets into th* blood stream. It it thrown off through th* pons of the skin sod the pons an plugged. I think it it rsther important to determine that because it seems to mo, from the slight knowledge that I have of the industrial application of halowax compounds in insulating wires, that th* plugging of the skin, if it is just aa outtide plugging, may take place either from handling a solid substance or from th* coating on the win after it becomes cold. I haven't heard anybody my anything about them hfanachuaettu eases of very seven dermatitis and I am not so sun hut what then was sons question of liver dam age then. Nobody has said anything about thorn at all. Thar* i* no question than 5 Gen Cor vec hell bee in s of v lure fact ben U xent veu' fum COB) inst tog out W else wax seqt iwfi ugsi_ ,'uiim: xn u jh > BBRN001960 I '* ; LEXOLDMONOOI831 el. 19, no. 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 course. I think thi* need* a great deal more study. Dr. Drinker, than you and your aaaoeiatoe have been able to give it ea yet. All I am eurioui about ia the way we can adainiater the protective labor law* ia order to protect both the employer and the employee. I licteaed with very great interest to the expositions of euggeeted pot* for the appli cation of halowaz, chlorinated naphthalene and diphenyl. It teemed to me that they left very much to be desired. I don't tee why the application of the halowaz com pound, if it ie neccctary, a* I asaume it it, to use thii rather dangerous substance, can't be done ia a practically closed pot. tt you please. Dr. Drinker, I wish you would ask Mr. Reeve* of the Rockbeetoe Product* Corporation to tell how they have handled it. If I am any judge of equipment and eafety devices they have come a* near to eliminating eotirely from the atmosphere all contamination from fumigated or evapo rated halowaz as anyone. All of the appli cation of halowaz, either in the melting pots or where it ia applied to the wire, is done under hooding and with ventilating appa ratus, and it aeems to be entirely adequate. wsx am hod a head start aa far ae the ventilating system was concerned, sines our* was already installed end adaptable to s compound with n benzene solvent rather than a melted haluwtx compound. In order to keep the fumes of a highly volatile sol vent under control we did develop a prac tically eomplete enclosure for tha container in which the compound was placed and exhausted that container in order to prevent any escape of the fume* from it. When we changed to the halowaz compound* we fol lowed the lame scheme of applying the compounds and used a completely enclosed pot. There is e hole in one side for the wire to go in end one on the other side for the wire to eoma out. There is enough exhaust suction oa the enclosure to prevent any fumes from getting out of the openings where the wire enter* and leaves. Of course periodically It is necessary to open the pot to replenish the compound or make adjust ments. In that case we have the ventilat ing system interlocked with the door that the operator opeaa so that when he open* it he increases the amount of air travel about ten-fold. Da. Rent Mxxxcx: What ia the veloc ity when the door ia opeuT Mm. B. H. Rrivra (Vice-president and General Manager, Rockbeetoe Products Corporation, NewHaven, Conn.): I will be very glad to tell of our experience if it wfll help the picture along. Our experience has been more or less parallel with Mr. Kafaner'a in as much as we manufacture the same type of wire. We have avoided the serious pic ture that he ran into, probably due to the fact that shortly after 1933 w* were using benzene as a solvent for asphaltic materials. We got into anemia difficulties with ben- teue fumes end had to install a complete ventilating system to remove all thoee fumea from the machines that applied the compounds to the wise. Following the installation of that equipment we were able to get a substitute for benzene, so wa got tt out of the picture. ' We an still in the saae fix aa every one cite is as far at finding a substitute for halo- wax. Than ia nous that wa know of. Con sequently when we went to the nee of halo- Mb. B. H. Recvts: With the door wide open, at breathing level the velocity is 300 feet. That ia the linear velocity. We cheek that every week oa every opening tt every machine with a velometer, a email instrument which is easy enough to operate and reads directly. Whenever the velocity fall* below that figure the pipe connecting that machisc ia taken down and cleaned, because there will be condensation inside the pipe to cut down the air flew and reduce the ventilation efficiency. Da. Rotsi, Mcxcxst: What do you think of that trap device shown? Mx. B.H. Rzbtbs: 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 passing the air laden with bslowax fumes through the boxes of rate then waa any depoait of halowaz in the enclosure. -**- ... - *-***-- ----------------- w 310 JOURNAL OP INDUSTRIAL HYGIENE AND TOXICOLOGY [&pt. IM7 Dm. Cacm K. Dxnrxxn: Yes. It is detcetahl* readily through tbe outflow pip*. Ma. B. H. Rzxvxa: Thoaa ia the far and probably didn't get tho concentration. Da. Cecil K. Daixzca: Wo change tho position of the boxea each day. Tho onoo furtheot away more into tho nearest posi tion, ao that over a period of weeks all are ezpoacd equally. complaints were bona flde. We hotao dif ficulty in handling sold wire and the men had no akin trouble. Yet when they did tbe same thing with poaaibly the application of heat in tunnels, ships and ao forth, they actually did develop trouble. We have used, of course, the icterua index In following some carbon tetrachloride eases and I wondered what you have to say about that. Ia that of no value at all ia the case of liver damage ia this material! Da. Emebt R. Hatsuist (Consultant Da. Caen K. Damns: I don't think ao in Industrial Hygiene, State Department of until it gets so extreme that we know it any Health, Columbua, Ohio): I would like to way. ask if it wouldn't be possible to put a cold water line around that trap and deposit it Da. B. L. Vosauaon: I did write down a 1 i all before the air escapes from the trap. kin. B. H. Rzsrsa: We have tried cool few questions that came to mind. Some of them have been answered and some are foolish but I shall ask them anyhow. ing the surface of the exhaust pipes in order It occurred to me that if triehlomapb- to concentrate the deposit in one place and thalene has been proved to be practically make it unnecessary to remove long lengths innocuous, isn't it a problem of research of the ventilating system. While we have largely for the Halowax Corporation to use found a alight advantage in doing ao it only that one material adopted with other hasn't at all paid for the expense. It is known chlorinated compounds to meet the much easier to take tbe piping down. Con requirements of customers? That is one sequently I doubt the possibility of remov of the foolish once probably, but I shall ing it all by moling the surfaces of tbe trap. just ask it. It might be possible, by building a labyrinth Furthermore, how long is it reasonable to of refrigerating coils, to collect it. But expect the liver to recover after it has been then you would have the problem of remov pretty well damaged. I talked to you and ing it from the coils after you had collected you said you hadn't worked that out with it and it would involve rather oompliested the animals as yet. procedure. - - Da. Cxcil K. Dnnrsxa: In that esse we Da. B. L. Vosauaon (Medical Director, aet aside a certain number of animals to Ceneral Electric Company, Schenectady, recover, after knowing that a certain New York): We have heard about tbe pos amount of damage had been done. Then sibility of preventing liver damage and skin we started to kill them but we invariably trouble among manufacturers of wires and ran out of rata before they ran out of lesions. cables and so forth, but like the old rhyme, We don't know bow long it lasts. every dog has fleas and the fleas have fleas, we also have customers who-use wires and Da. B. L. VosBcaox: Have you given cables in tunnels, in enclosed spaces, splic them calcium and glueoee as you would with ing them together and doing all aorta of carbon tetrachloride? things. I am not at all certain that ww know what the concentration of these chlorinated Da. Caen. K. Daman: Not yet, but we hydrocarbons ia under those conditions. are doing an experiment now with one group About the time we ware having ao mush on a very high calcium diet and another trouble at our York factory aome of our group on a ealeium free diet. The whole customers began oomplaining. We thought question of ealeium in the diet, of giving we were having a hysteria of halowax mania milk daily to these people may be worth throughout the country. Some of their while. fOl.i D queS' what bilit; chlo: M simp from the t I tbi toot thet Tbe fndu chlo: Tl wbic our i will Drin dem: com] some we c remc uent and a lot able one A: with theti some com: que: the whe to 1( r. SOIU the D mor. on a. all GBRN001962 LEXOLDMONOOI833 wl. J#, m. r) EFFECTS OF CHLORINATED HYDROCARBONS 311 Dn. B. L. Votsumon: I jolt 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 ujr as to the possi very important employees. It would seem bility of usinf only this one innocuous that it would be worth while to give serious chlorinated naphthalene. consideration to seeing that conditions are proper and suitable for them to continue Mb. Sawnroan Baowx: That would simplify our problem exceedingly, not only from the commercial standpoint but from the toxicity standpoint. But if we did w I think that Mr. Kaimer would be the first to object because he wouldn't be able to get the technical effects he desire* in the csble. working for you and that they have proper treatment. In other words, I don't believe that is n 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 may be in error. The same thing applies throughout all the industry where we are using these higher bin. Saxbvobd Bbowx: I wont to take chlorinated products. this occasion to express on behalf of the The problem as we see it, and it is one Halowax Corporation my thanks for the which we intend to study further (we have excellent cooperation we have received from our program for this continuous work that various state authorities and our customers will be done under the direction of the ss 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. we eould take hexaehlornaphthalene and In collaboration with the Monsanto i remove 1 per cent of some unknown constit Chemical Company we here a much more uent with which we are not now familiar comprehensive program in view to carry on. iH * and eliminate the toxieity, that would be Therefore wc want to continue that same a lovely solution. Whether we will ever be type of cooperation. able to attain that I don't know. That is There is one thing that I went 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 :a 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 pert of the workmen in the plants commercial developments. It is largely a where these inspections are made. Mr. question of timing at to when you should do Hemperly 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 he* made. I know that be would be glad *:y to lean that first. to relate them and give the benefit of bis j. experience to the heads of any of these etate Da. CsctnK. Dnuran: Unless there is some other important matter I will declare the meeting adjourned. departments who will have the direction of this work. Otherwise I ran see w-here we will be unable 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 are shooting for ever the next sev up on 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 yuan. le .nj .*Ui i i I i "w m GBRN001963 LEXOLDMONOOI834