Document EdZ0p6Ew10O5qmeJ8z4EqGkqx

THE JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY Vfetcsns 19 SEPTEMBER, 1937 Number 7 THE PROBLEM OF POSSIBLE SYSTEMIC EFFECTS FROM ' . CERTAIN CHLORINATED HYDROCARBONS* C.Cien, K. Drinker, Madeleine Field Warren and Granville A. Bennett Bipartment of Physiology, Harvard School of Public Health and Department of Pathology, Harvard Medical School, Boston, Mass. A- HE use of chlorinated naphtha rapidly and thoroughly as possible.! Tlenes and compounds of allied pharmacological possibilities is lu brief these cases were as follows: Patient I. Male, age 21. The previous extremely wide, and with the steamdyedical history of this man was in no way growth of the use of electricity is cer- significant except for the fact that he had .taia to expand much farther. For jean it has been known that many of .Hm* compounds cause a troublesome {.me, and there is a large literature pro this phase of the subject. Our an attack of jaundice about 6 weeks prior.^o his fatal illness. Late in December, 1030, he became badly constipated and had much abdominal pain and distention. When ad mitted to the hospital he was slightly jaun diced and was evidently very ill. He was fcweatigations have not been concerned somewhat anemic and his skin, particularly lift chloracne but with the possibility f systemic effects following ingestion inhalation of such products. In the upon the arms, face, chest and back, showed many pustules. Ho died after a brief period in the hospital, and at autopsy was found Vo . living of 193G, the Halowax (\>rj>ora- t The Ilalownx Company makes many ' tin, a division of the Bakelitc Cor- products besides chlorinated naphthalenes, and it has come to our knowledge that all of on, called our attention to three these products are indiscriminately called t cases of jaundice in workmen "halowaxes" by purchasers and users, and are lumped together os possible causers of chlorinated naphthalenes and acne and even of systemic disease. Since J-Jrorinated diphenyl, and re<piestcd "hnlowax" is merely a trade designation, care should be taken to describe compounds the subject be investigated as by their chemical names and thus avoid condemnations which are both troublesome >: Hweived (or publication June 30, 1037. and misleading. ' if 2R3 s WATER PCB-00049349 284 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY have a cirrhosis of the liver with acute yel low atrophy superimposed upon it. This man had been exposed to low concentrations of vapors arising from a mixture of tetra and pentachlornaphthalencs, together with approximately 10 per cent of a refined chlo rinated diphenyl. While both he and others ` engaged in the same work had chloracne, there were no other disturbances of health in fellow workmen, nor was there any pre cipitating cause for the acute yellow atro phy such as treatment with arsphenamine or exposure to dangerous concentrations of carbon tetrachloride. Patient t. This was a young man who died in February, 1936, after an acute illness characterized by jaundice. He had been exposed to fumes arising from a mixture of penta and hexachlornaphthalenes. There is no record of chloracne. The patient worked with a large number of other people of whom but one (Patient 3), a close friend, had significant illness. Pafienf S. Another young man employed with Patient 2. He became jaundiced in March, 1936, and died after an illness of 2 weeks. A careful autopsy resulted in a diagnosis of acute yellow atrophy of the liver Here again no history could be ob tained as to a precipitating cause, and there was no record of preceding attacks of jaundice. In addition to these three very re cent fatalities, we have learned of four other possible cases, none of them fatal. All of these have had jaundice and the entire group consists of iso lated individuals who have been picked out of large groups having the same exposure. In but one instance, Pa tient 1, is there record of antecedent disturbance of health, and the general health of fellow workers has been good. Such cases have not been reported in the medical literature and only occa sionally can one find reference to sys temic effects of any sort. For exam ple, Courtois-Sufiit (1934) reports on work done by Ton mine and his asso ciates (1934) who examined til) workers who had been exposed to trichlej, naphthalene. Of these 13 wore to have mild digestive complaiiS anorexia, nausea and vertigo, Courtois-Suffit remarks finally, r sorption is certainly possible and have for proof of it some of the dig tivc and general complaints wh have been due to it. But they app to be of little consequence consider the mildness of the digestive troubl^f and the absence of respiratory nomcna." In Tourainc's cases the exposurestnv to a trichlornaphthalene, whereas th*Jt American cases of acute yellow atrophy were exposed to compounds of higher! chlorination. Our own experiment*! indicate that trichlornaphthalenea i quire enormous dosage, far beyo anything encountered in industry, order to produce liver damage. T< eky (1927) reported a number of case*} of chloracne in persons exposed chlorinated naphthalenes with a chlo^ rine content ranging from 14 to 53 pJ cent. He found that the lower chlorine content the less the acnA Mittclstildt (1935) examined a number! of cases of chloracne due to trichlof| naphthalene and reported a numberofj vague general complaints but nothing' in the nature of serious disease. garding his animal experimentation, Lehmann (1919) reported that anhjj mals fed chlorinated naphthalenes re*^ fused to cat after a time and that,*' whether poisoned by inhalation or by^g feeding, at death showed "peculiar"'- lesions in the liver. Flinu and Jarvik (1930) gave subcutnncous injections enormous doses of chlorinated naph*l thalenes dissolved in paraffin oil tojji rabbits. The compounds used as follows: ^4, it, no. n t.i-1-1 j A mixture of ' ' naphthalene 2 A mixture of chloruaphth . 2. A mixture of chloruaphth In adiBHoti, suhli ' P) were collected ^lubcutnneously. . . None of the anin the sublimate from after 2 months wen autopsied. The fii mats receiving (3) < day and the last d' Those receiving th were even more Autopsy in thes linking changes cribed, cntirel acute yellow atn Wggcstive to cans rlude that "eerta thalenes or imp them are capable trophy of the liv At the begim Flinn and .Jarvik fart that there I of acute yellow in men working w thalenes Imt givi to them. These the same as tie beginning of this Cue may sut literature u|hiii these substance:- b Will, the ti"u of ncuti- v m,d Jarvik (15)3 or even suggcsi ul)<n human hr 2. Their is r that the degrn 904314 WATER PCB-00049350 A(S, KfTKtTS Of CfU.OItlNATKI) IIVDIiOt'AltItON.S 2.3o ' .4 mixture of tri mid tetruchlor uificaut in relation to the production 1 SSsk&iv ' naphthalene. of acne. In the work of Klimt and t, A mixture of tetra and penta- Jarvik (I93ti) the com pounds produc 1 chlornaphthalene. ing serious liver injury were the most, \ mixture of penta and liexa- highly chlorinated of those tested, chlorifaphthalene. though the chlorine contents as given addition, sublimates from (2) and by analysis vary surprisingly little. m irere collected in oil and injected 3. There are no published figures taneously. upon the amounts of various chlorin Hone of the animals receiving (1) or ated naphthalenes in the air which will jublimate from (2) died, and even produce injury of any sort, and while 2months were quite normal when the work of L-limauu (1919) and of i jntopsied. The first death in the ani- Klimt and Jarvik (1930) point to the v*mb receiving (3) occurred on the 12th liver as a possible site of injury this V bjand the last died on the 2(ith day. indication rests tt|H>n such extreme receiving the sublimate from (3) dosage as to fail to apply directly to 'Jt'wrr even more severely affected. human exposure. ^(Autopsy in these animals revealed linking changes in the liver, not, as Kxckhimkntai. W'ottK tfarribed, entirely characteristic of In appraising the possible toxicity of 7,1 irutf yellow atrophy but sufficiently any substance met in industry it is mggostive to cause the authors to cou- first necessary to determine tin* prin 'dode that "certain chlorinated napli- cipal route of absorption. In tlie ease Uulcnes or impurities contained in of the compounds under consideration are capable of producing yellow there can lie no doubt that inhalation ..tlrophyof tin* liver in the rabbit.'' is their chief means of entering the At the beginning of their pu|ier, body. They are used hot in a great inn and Jarvik (1930) mention tin1 variety of operations and volatilize in that there have been three cases varied degree. They are often applied 8cute yellow atrophy of the liver in solution in such volatile solvents as men working with chlorinated napli- carbon tet raehloride and toluene. The 41ttlencs but give no details in regard amounts reaching I lie air under such jjto them, Those cases are undoubtedly circumstances are hardly deieelable. xame as those descriheil in the It will however In* shown that- earl ion ^beginning of this paper. tetrachloride adds In the toxicity of 1 may s,;ln,"nri7.e the meagre the chlorinated naphthalenes and allied 'ffcfe'N ^^ture upon systemic elTeets from compounds, and if there is pos-ibility M!l,stil'",,s a-s follow.-: of inhaling llie-e enmpnmiil- ill other I ^'th the exception of the men- parts of the factory then inlialalinn of ` acil*<' w atrophy by I'Tum Narvik (19311) there are no reports , -Of e\en siigge-t ions of -erious elTeet - VPn hiiiuan `iiet' ng-. 2. that The.rree is evideliei ti\e (Ulegree i (Tricky, uiual ii in I'.I.'T i is -\g- carbon tetrachloride adds a decided hazard. I'nder -mli eireum-taiiees solvents -Ill'll U- toluene -Imuld he 11-eil. < Ib-ervat ion in a number nl plants eau-es II- to feel that even though t":l-.. 1 '' . r * 1 'J| .HU'IIN'AI. or IN'IM'STI! IA1. I [ V(!I MX K AXIl T( >.YI( '( )|,( Hi V workmen may lie extremely flirty :m<l careless, <*>iii}i:tfitti\ <-ly III lie of I lii''c wnxcs is eaten. They arc tenacious substances, insoluble in water, and if they get oil the hands they stick there, and are not transferred to the food. Skin absorption is the third possible means of entering the body. It- may occur hut at host must he slight when compared to the steady inhalation of finely divided or gaseous material in the air. lion. They llirive upon a diet \-i>rv similar lo man, and in I lie i'iise of | chlorinated compounds it is pnssili|P that- diet may lie very significant Finally, their normal eliaraeteristi^' have been described so well as to make the detection of abnormalities both, easy and certain. , Mcthml of exposure. -The inhalation experiments were carried out in four large air-tight wooden boxes, each capable of holding ten rat- cages, size' 'n:. I. Front view and inflow end of two boxes with rat cages in place and doors upi-ii. Inhalation experiment" are then the most important sources of information, lull to them we have added a certain number of observations upon ingest ion and subcutaneous injeetinn of various compoiHK I". Iuliolulmu /'!.i /ii i iiiii tils ,\m nulls. While rat" have lu-en employed lliroiighoiit. 'I hey permit l lie use of a large mimlier of animal" in a relatively -mall inhalation iii"lalla- -`2* x 22' x M', in two tiers of five cages eaeh. When the experiment was liol in progress (lie doors were o|M'iic(l wide and the cages kept in place (figure I). Al the ('enter o| one end of each hoX the iidlow end air was introduced through a pipe 7 inches in diameter (figure 2i. Faeli Imx was <<|iii)>| with an individual variahle-'peed elcellie lilouer which blew I he air through -evei.il leel of 7-ilie|| |lipe Iicfiire ('liter- ret- (' i,,g 'I"1 meter > ........... " the flow of air m ^..Id headiusted a from a calihralim deflector placed at pipe into the box v ^ire a uniform d stream of air to tin At the opposite i outflow end --the was exhausted thrfitted with a dampa large central e.xli About 4 inches f the 7-ich pipe inti of the substances ilticed into the i cially designed | (figure 4), 7] inch 1$ diameter of 1 ( in hold the heated u were made with a that extended to top of the flask u this fitted a short length. Thi' 'hm into a large iiiMhtightly into a hole pipe mi the under flask in turn was i heater made to , below the side nr; top. Rubber till side arm w ith a e voir and a gentle through the mel faction and assur blto eai li Ihi'k vva wiitigr.'ide iImwii hept in pini-,. and time aliovi- (In"hieli it |,;t--j /; A|ipro\ini;it,.|y chlorinated i,;,pl,i 904316 WATER PCB-00049352 *4. 19. " 7'` rs <>i-' < iti.c m; in a i i:i n vnuor.uii'.iixs 2X7 elilnrinaled diphenyl were |il:ic>,( in the Imitnm ul'each flask and inelied in the electric heater. Fresh samples were used every other day, lad it was often found necessary to add 20 uni. of now material even after one run since so much had sublimed. Whatever the case, the collected sublimate was I'm. 2. Kleetric heater fur iiiaiiitaiiiiiut < hI<irin:i(i<I i'Min|miniils at a eniistaiil.loin|icr,a!arc in |il,'ii'i` at inllmv eml of Imx. nl\\.'iy- removed from the upper pall id I lie Ihmk and a clean lop iiM'd each day. No simple was ever Used for mure thall two runs The l!a>k pill' I lie eon leu I ' vv as care fully weighed al the liemmiilij; of the rim and al the end, and llie lo" in ueielil Used III calclll.'ile (lie .iver.e'.e 2KS ./(it'k\i. or ixm sTitiAi. itvoikxi-: axd roxiroi.ociv in. p>- is.?? '. . rl amount in ii ciiliic meter of air per minute as determined liv a series of I'm. 3. Outflow end of two boxes showing connections to exhaust system. I n:. I. IS rex glass Mask llowmeter readings. The figures 0|>. taineil were not absolute In-cause 0f slight variations in the air flowing through the boxes and heeauseof de|Misition of material on the tlicrmometers and on the inside surfaces qf the hox, hut they cheeked 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 Imix doors wen* tightly closed, air bubbled through the flasks, and the blowers turned on. This was the beginning of the exposure |>cri(xl. By means of rheostats on the fans ami dampers in the outflow pipes, the amount of air Mowing through the boxes was adjusted and an attempt was made to keep the four boxes as uniform as possible usually between fXJ llio and 17"> e.f.m. In the first group of experiments the following substances wine tested: 1. A mixture of trichlnmaplilhalencsphisa trace of tetraehloriiaptbalene. Chlorine content 19.0 per cent. 2. A mixture of peuta and liexacbloruaplit balenes. ('hlorine content (>2.(i |ier rein. It. A mixture of 90 per mil |H-nta and bexaeblomapbl balenes phis ID per cent refined clilorill* aled diphenyl, ('hlorine coil* tent <13.0 per cent. -I. Chlorinated diphenyl. Chlorine coulenl liA.I) per cent. I he compounds were selected as rc|>" re-enliug a rertain range in chlnriiiaI i'Ui 'iml .'dsn I leentl'i` ol t heir iudu-lrial imp' in d lu each iu'lanie Ml ant* \pii-i d, III lal- being placed ilt e: Thev were fed 1*11 ritl t.'-:-Vo Chow supr C* <yp, niilk and c 'ysx-y.Ttus firs1 8roi; on July p^ Mrnoauie to num rfy ^jomaphthalen & tetk Theexpc h' ^pounds cea `;r . ISth. On Oct( " ' gro animals wc ... ion from group after 2 i- ) 15th, in order tc Co*DITIOSS Mais Trieblornaphthal UUmcbtorn&ph ftaU and hexac penta and tee* plus 10% i V. t Chlorinated diael period would the affected .{roup 3 weri oposure on k* examinat .C.*rhe avera hours di h, Each mornir ' teased, and C ' 4:00 p.m. t! righed, etc . fortuity of tufted on uoA'ce 1 WATER PCB-00049354 EFFECTS OF CHLORINATED HYDROCARBONS 71 2S9 fjijB* Chow supplemented by lettuce, milk and cod liver oil. first group of experiments was oa July 1, 1936- and the last to number 2 (penta and hexacawmphthalenes) was on November } The exposure to the other three ;.|BOpounds ceased upon November 'jyj, On October 15th representa'f^rt gnimals were taken out of expom from groups 1, 2, and 4 and were r-Ufled after 2 months on December 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 Caramoss Maintained in Inhalation Experiment from Jolt I to November l(i and 18 CHLO RINE temp. CONTENT AV. CONCENTRATION TOTAL EE- AV. OAILT POAURE % flC. mf./cu. rr. range koure Aour* ^TrteMornaphthalenea plus traces of ;:/:ltfr*<hlornaphthalene . rv* 49.9 150-160 1 31 High 2 60 Low 0 10 1S90 1G .fw* and hexachlornaphthalcnes..., 62.6 160-170 1.16 High 2 19 1804 Low 0 51 16 penta and hexachlornaphthahat* plm 10% chlorinated diphenyl. 63.0 105-175 1 37 High 3 17 V- Low 0 G4 1890 16 .^BfartnUed diphenyl. 65.0 165-175 0.57 High 1 19 1S96 Low 0 23 1G A tnod would bring about recovery in effected livers. Animals from 3 were similarly removed from on October 4th and killed examination on December 4th. averagc length of exposure w;us ^'^ur3 daily for G days a week. morning at about 9:00 exposure &n^ between this time and Atth P,rn' the rats were cleaned, fed, ' e^C- or<^cr t sccurc uni- f exposure the cages were on a regular schedule, since showed that under the temperatures used no deconi|)osition occurred. Table 1 shows the tcm[>crnturos at which the various substances were held, the average concentrations per cubic meter of air, and the average exposures from July 1 to November 10 and IS. The concentration of chlorinated naph thalenes and chlorinated diphenyl in the air of workrooms.--Table 1 shows that animals have been exjiosed to varied concentrations of the substances under &; fed Ml*' * `S*s| ' lisn'j $$i! *`i. .|- .. V %r.`: it?.!-'; ; a#tn i;-n n - 1 i*f' ; M' ; Sb`.i; \, \m :/; tfec-: fe\-; M-ilip. . |p!: ' ' *? tm- 290 JOURNAL OF INDUSTRIAL HVGIENE AND TOX'ICOr.OGV ISepi. 1J]Kh1P^'`*?i*L if, no- tost. Tlic concentrations employed may bo regarded as fairly representa tive of industrial experience. Prior to the initiation of inhalation experi ments a number of estimates of chlo rinated hydrocarbons in the air of dif ferent factories were made and the in question is passed over heated p(atjJ> nurn in an elec! rically heated 9'iatti; tube and the effluent gas scrubbed i^ a column of glass beads moistened uit^ sodium carbonate containing a tracer 1 sodium sulf\te. The beads are thl washed down and the chloride deter. suction max 7 MU. IN31CE OlAft SOU D CRASS MAAS mnoiAH. 55' & zcn. CLASS WML MOT DRAWN ro SCALE 35-Ot ii. seen. -- 3" ---------- sen- ICM.^ f*7 jnniHSiDE DIAM. ,-J___ PIPETTE JT~ TIP eensviNce furnace wff(l NOtCHHHe/ponc)ewiea 7Mfi rntoe OIAN. PLATINU6M" *FOIL PAOC-OKIONIG" IS. 24 a 3.01 * 0.002 54 CM. Fta. 5. Dimensioned sketch of combustion tube and absorption apjmrutus. concentrations chosen for inhalation experiments depended on these exami nations. The technic of analysis and the apparatus employed were the work of Frederick It. Millhiser and William K. Ilemperly. The method and apparatus used fur determining concentralinus of chlorin ated hydrocarbons in air were adapted from well-known procedures. The air mined nepholomctrically as silver chloride. Tebbens (1937) has recently de scribed a method and .apparatus which should be equally satisfactory f<ir ,*1'9 work. In figure f> we show a dimen sioned sketch of the combustion tub and absorption apparatus as used b) ius in both our laboratory and fie'" problems. The absorption tube 11 icanewhat Xebbcns'3 devices ai In both ^stated h; and odium cs In our cfl gpt to be less than quently t actually f ao snail t either gn For this r use the m b sensiti M 0.1 mg It is d should e: eonversic pound t< Rjbseque unless th low. An b that t any chic defermin distingue gases but the resu puted in At the fonnatio rinated i different instance repeated the amc those uf must b< The f&tua aui by Wills The. eqc auction p '.TWIP'.'W/ ~ T-'iTOT** 1 t' y-3?.o WATER PCB-00049356 .ivii-tfUj tIrW't.Vr1i'S;F-v*A-v''..fT:.i'-.Vv;?.'VsSV-;*;'!.. S'Pt. ti sQt rhttfcj tarts :f.. 7\ EFFECTS OF CHLORINATED HYDROCARBONS easier to wash down than is ilVbbens's but the essentials of the two ` are the same. ju fjoth cases conversion of the chlo rinated hydrocarbons to hydrochloric and subsequent absorption as `^iedhim carbonate should be complete, our case concentrations in air are ipt to be very low--the objective is Jgg than 1 mgm. per cu. m. Conse.tqoently the amount of silver chloride S5actually formed in the final reaction is 0 small that it can not be determined ther gravimetrically or by titration. For this reason we have been forced to ; oe the nephelometric procedure which ' fa sensitive to concentrations as low uO.l ragm. per cu. m. of air. It is doubtful if the sampling rate should exceed 1 liter per minute as c conversion of the chlorinated com| pound to hydrochloric acid and its Bxbsequent absorption arc not efficient ttaless the velocity of the gas stream is few. Another precaution to be noted k that the method is not selective-- toy chlorinated substance will be determined. Furthermore it does not distinguish between solid particles and ' P but determines them all alike and results must, of course, be com{fwtedin terms of total chlorine. . At the present time we possess in *' "^nation as to the amounts of chlor>/*jjp*ted naphthalenes in the air of 30 >\~"erent plants, and in a number of dances the measurements have been r ^^peated several times. l're(|ueutly Jhe amounts have been greater than > wose used in our experiments, but it be remembered that the rats a?1"'- txtnif^e,C0Inbu3Uon and absorption appa*aited to field sampling is now made u|(on Products, Inc., Heading, Pa. equipment includes flowmeter and 00 PUxnp with a carrying case. have been exposed for Hi hours to an atmosphere constantly impregnated with the substance under tesjt, whereas, human exposure is usually a variable quantity, intense for a short time and then negligible. It is our opinion at the present time that the concentra tions of chlorinated hydrocarbons used in our experiments would be dangerous for workers in the case of compounds above trichlornaphthalenc in chlorina tion. Fortunately it is easy to venti late processes of manufacture which require those substances and to reduce air contamination practically to the vanishing point. Such treatment of the problem at once removes both the possibility of systemic poisoning and the annoyances that arise from cases of acne. Results of Inhalation Experiments. 1. Animals exposed to a mixture of trichlornaphthalenes plus small amounts of tctrachlornapthalcnc. Living animals were apparently en tirely normal. Autopsies |>crformcd near the end of ex|>osurc seemed to show slight swelling of the liver, and microscopic examination occasionally showed swollen and hy|>ergranular liver cells. The changes were, however, never more than slight. 2. Animals ex|>oscd to a mixture of penta and hcxachlornnphthalencs. No abnormalities were observed in (he living animals. Rats were killed and uutopsied every <> weeks. In the (irst animals sacrificed liver changes were observed. These were swelling of cells, slight granulation and hynlinization. In September and October these conditions were somewhat more ad vanced, and in November the process became stationary. There were highly -Hi ... -i 1 yV- s m A'.; % i 'S 904321 -^^&355iSSe WATER PCB-00049357 r 292 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY *'*. it-: granular cells, hyaline inclusions and mitotic figures, but no more than 2 months previously. 3. Animals exposed to a mixture of 90 per cent penta and hcxachlornaphthalcncs plus 10 per cent refined chlorinated diphenyl. No abnormali ties were seen in the living animals. After 0 weeks the livers showed changes similar to those in the animals exposed to penta and hexachlornaphthalenes. These advanced in grade during August and September and then became stationary. 4. Animals exposed to chlorinated diphenyl. No abnormalities were seen in the living rats. After G weeks' ex posure there was slight liver damage which advanced during the next 2 months. The changes consisted in slight to moderate swelling of the liver cells, an increased granularity and many mitotic figures. Hyalinization was always present as a result of inhalation of chlorinated diphenyl. Summary of the first inhalation ex periment.--In these experiments care ful observation of appearance, body weight, activity, blood, and urine showed no abnormalities of any sort. Yet after 0 weeks' exposure all the compounds with chlorination above trichlomaphthalcne caused minor de grees of liver damage, and no changes whatsoever in other organs. There was no acute yellow atrophy or any thing suggesting it except that a slight degree of liver damage was always present and was quite clear in the liver sections examined microscopically. This damage had no detectable effect on the health of the animals. They held their weight, ate and Irchaved normnlly, being in every respect similar to the many people who have been exposed to these compounds without illness of any sort. ' The functional appraisal of the fiJ damage caused by certain chlorinated naphthalenes and by chlorinated diM phenyl.--There are no tests of livers function useful in such minor degret^ of liver damage ns were produced la*! these experiments. Indeed the anj.1| mats resisted the injury so perfectly! as to display no abnormalities except^ upon histological examination of tb liver. The situation was perhaps similar to that met in industry, \vhere,1 barring acne, the health of workers ia| these compounds has been good with the exception of the fact that in iso?) latcd instances jaundice has occurred! which upon at least three occasion*I has gone on to acute yellow atrophy. Jj During recent years this disease I been seen following administration carbon tetrachloride, arsphenaraine J and cincophcn. In the case of carbon tetrachloride it is known that a loW,| calcium diet and alcohol favor the pr duction of liver damage. For tbj acute yellow atrophy that occasionally^ complicates use of the other two drugij no cause can be assigned. One can produce acute yellow atrophy with| arsphenamine, but somehow or otha| this now and then does happen to pa*j tients under antisyphilitic treatment.| It occurred to us that something of the same sort might be involved in thi*^ problem. The human cases have been ^ scattered ami few. They have been isolated instance's out of largo group* % of healthy employees who have had equal degrees of exposure. It was our^ idea that perhaps many of these pooping got liver changes such as existed in rats, changes not recognizable throug ^ my n1< mtion. Rich cl ^"..disturb not a .which i ".this r< ':r. tc Kno bd l> -jfight i . we dec ^wbsta ' itnicti ikoho tnatioi to- chlorit ll: per ki Bonne 07 IgnQ.75 c .Thi jtjfi mala < ift i*: %d;-'22 WATER PCB-00049358 i' , 1 ti, "- 71 effects of chlorinated hydrocarbons 293 mean3 other than autopsy exami- Uon. If. upon the substratum of changes, they got an acute liver : ^turbance, acute catarrhal jaundice, 1 died Nov. 10th between 5:00 and 10:30 p.m. 5 died Nov. 11th between 4:30 and 10:30 p.m. 1 died Nov. 11th between 4:30 p.m. and K got very common disease but one 9:00 a.m. Nov. 12th. ' i any of us may experience, would 2 died Nov. 12th about 1:00 a.m. r relatively innocuous disease go ifcf to acute yellow atrophy? Knowing that our inhalation rats 1 died Nov. 13th between 5:00 and 10:00 p.m. 4. Chlorinated diphenyl. Fed at 10:00 a.m., Nov. 10, 1936. 10 rats. liver changes, but changes too 1 killed Nov. 10th at 10:30 p.m. (almost AA.'jggjrt to cause recognizable symptoms, dead). decided to test their resistance to j^atanccs known to cause liver de: ' itniction. Carbon tetrachloride and 2 died Nov. 11th between 4:30 and 10:30 p.m. 1 died Nov. 12th before 8:30 a.m. (stiff). 1 died Nov. 13th between 9:30 and ; alcohol were selected. Having infor- 11:00 a.m. nation that 1.0 cc. of carbon tetraddoride plus 1.0 cc. of ethyl alcohol * per kilogram would kill 14 per cent of sormal white rats, we reduced the dose \ to 0.75 cc. carbon tetrachloride and 1 died Nov. IGth between 10:15 p.m. Nov. 15th and 9:00 a.m. Nov. IGth (stiff). Controls: Fed at 9:30 a.m., Nov. 12, 193G. 10 rats. 1 killed Nov. 13th for normal liver. ;V 0.75 cc. of ethyl alcohol. This tabulation summarizes into the This mixture was given by stomach facts that: Y tube to the following groups of ani ' sals and with the results found in the following tabulation. >4tp*V iete fed 0.75 cc. per kgm. each of carbon tetrachloride and ethyl alcohol by , etomach tube 1. No normal rats were killed by carbon tetrachloride and ethyl alcohol. 2. No trichlornaphthalenc exposed rats were killed, and this finding agrees with our inability to find lesions of moment in the livers of the animals that inhaled this substance. .! Trichlomaphthalene plus trace of tetra.Mmmphthalene. Fed at 9:00 a.m., Nov. 1938. 10 rats. No deaths. ^ Penta and hezachlornaphthalenet. Fed ; : a.m., Nov. 10, 1930. 10 rats. . 1 died Nov. 11th between 4:30 and 10:30 p.m. 3. The penta and hcxachlorinatod naphthalene, the mixture of these with 10 per cent chlorinated diphenyl, and finally the latter substance alone seem to have produced conditions lowering the resistance to an agent capable of 1 died Nov. 12th at 3:20 p.m. iiv.' 1 di?d Nv. 12th at 4:30 p.m. ' 1 died Nov. 13th between 9:30 and 11:30 a.m. I died Nov. 15th between night of Nov. 14th and 12:30 p.m. Nov. 15th. 2 producing serious liver disease. 4. The solo lesion produced by this test of liver function was acute yellow atrophy usually accompanied by jaundice. died Nov. 16th between 10:15 p.m. 1 Nov. 15th and 9:00 a.m. Nov. >j, 16th (stiff). . ^ per cent pentn and hcrnrhlornaph- and 10 per cent chlorinated diphenyl. n 10:00 a.m., Nov. 10, 1936. 10 rats. This test of liver function was ac complished with a substance which itself is an organic chloride and curi ously enough it is -tIk* only substance we were able to find that was effective. 294 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY (5ep/. In animals with the minor degree of liver injury which lias linen described we were unable to produce acute yellow atrophy or any variety of liver effect with arsphenamino, cincophen, butyl chloride, ethylene chloride and tetraehlorethylone, but carbon tetrachlo ride was uniformly effective in dis closing the existence of liver damage. Recovery from liver damage following removal from exposure.--Animals ex posed to trichlornaphthalenes plus traces of tetrachlornaphthalene being practically normal on removal from exposure need no consideration. In the case of the penta and hcxachlor- signs of liver injury will |>r> m&njj mouths in returning to normal. The effect of high concentrations trichlornaphthalenes with traces of Ulr$ chlornaphthalcne.--The first group , inhalation experiments showed th this material in concentrations aver ing 1.31 mgm. per cu. m. of air relatively innocuous, judged both br|j direct observation and by the carboaj tetrachloride test. This is an tnJ tercsting fact since such compound*^ cause acne, though less potently thaa^ substances of higher chlorination.^ In order to explore the matter further 1 one of the inhalation boxes was arranged . The f finda Jtcrc c i-T' age don hut in ported i tould nothing TABLE 2 Conditions Maintained Dvnixr. Inhalation of IIioii Concentrations op THICII LORN A PIITII ALEXES PLUS TETRACIILORNArilTIIALENE MATERIAL TEMP. AT, CONCENTRATION OP AIR IN HOX TOTAL AT. 04&f{3 EXPORCRC xpo<cq`agi Trichlornaphthnlenos plus traces of tetrachlornaphthalene c. 137-200 mff./eu. n. 10 07 rang* High 10.10 Low 5.78 Aourt 1232 jUwi 16 & CosniTi Penta a: 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 of removal from exposure but on the other hand 2 months were insuffi cient for recovery. The same findings were true of the mixture of |>ont:i and hexachlorinaled naphthali nes 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 c\|X'ct that an individual showing any so that fumes from four glass contain-^ ers were delivered to the nir line instead of one. This resulted in the condition*jj shown in table 2. The animals sub-^ jeeted to these conditions showed no-1 clinical effects of any sort. After lj month the liver cells were slightly^ swollen and over-granular and the were occasional mitotic figures. Thes?J changes were similar to the early effects of more highly chlorinatedcompounds, and progressed only slightly during (he third and fourth months. When rats in this condition, were given carbon tetrachloride and alrohol, in some instances their livers showed massive central necrosis ana *. Effiem b "for m! killed 1 and 8 expose killed fatty with r iruma 904324 16 WATER PCB-00049360 24 m ?l EFFECTS OF CHLORINATED HYDROCARBON'S 295 olbcra this did not develop. Fifty mire used in this experiment run1 moy eonrludc that while the tri ^'i^uphthafencs arc in no degree as u those of higher chlorination fyftfrT M* not ent`rc*y fr.cc fro,n efleets yje liver if high enough conccnare inhaled over long periods. IF IS;fl, effects of high concentrations of and hexachlornaphlhalenes.-- ^i^re can be no doubt as to the damf^done the liver by these compounds Jfat in the concentrations so far re^ farted no symptoms were caused that Heeold be recognized clinically and ' Mthing approaching acute yellow the liver after do days of freedom from inhalation. Ft is thus evident that penta and hexaelilornaphthalenes are markedly toxic compounds and that recovery from their effects is extremely slow. The effects of penta and hexachlornaphthalencs, the mixture of these with 10 per cent chlorinated diphenyl, and of chlorinated diphenyl alone, when inhaled in low concentrations through an 8-hour day instead of a 16-hour day as in the first experiment.--Since steady human exposure to any of the compounds tested would invariably be for 8 hours rather than 10-hour periods, a further TABLE 3 n QttOtTlONS Maintained during Inhalation of Hioii Concentrations of I'enta and H EXAC.IILOnNACIITHALEXES MATERIAL* . IVU tod hexachlornnphthalencs %* TEMP. c. 137-193 AV.CONCENTRATION or aiu in ynx mgmj.fu. 8.S3 range High 1-1 0 Low 5.73 TOT V L AV*. OAILT CXI'OAONC CXPOSCHE Aouri ous Xau/i 16 ullrophy occurred except through the of the carbon tetrachloride test. ^.Qa December 1, 193G, 80 rats were Tiabjected to the conditions sum- i,*fued in table 3. This expermont terminated on January 21. All of iM* animals lost weight and appetite deaths began after 8 days of expo T' Fifty-five rats died, most of heavily jaundiced, 8 were killed ri i Rncroscopic examination, 9 were :^Ued by the carbon tetrachloride test ;*sd 8 lived through the period of r^^0sure- The livers of the animals ^r exaniination showed marked ^ degeneration, central in type ^*^tlocrosis ^ liver cells. Surviving ,TMnnal3 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. Kighty 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 0 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 the animals exposed for 1G hours under the conditions set forth in table I. The carbon tetra chloride lest was uniformly fatal to them and one must conclude that con- ISiT: 14 g ! 1 I,.v'li'A""* 'i' SSL l* I 9.' 1 l.-NSy> S'sei-'AT V'.V:- WATER PCB-00049361 am T JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY i#/. /*. M ccntrations of those compounds such as wore employed cause a certain de gree of liver damage even if inhaled for but 8 hours daily. This injury is resisted successfully by the rats just as was the 16-hour injury but it is none the less there and destroys the ability of the animal to resist the carbon tetrachloride test. Summary of inhalation experiments. The findings that have been described briefly will bo amplified upon the pathological side in a further paper by Dr. G. A. Bennett. What has been given is, however, sufficient to indi men never inhale enough of any these substances to get acute y0||Q atrophy. They may, however, a a substratum of liver damage upoif which acute yellow atrophy may velop. Experience in a number plants has shown how easy it reduce concentrations of those eo pounds practically to the vanishing point, and every effort should be i ' to attain such conditions. Gross Feeding Experiments The various compounds used ground ns finely as possible and with a standard balanced ration f'$ carbons r feeding a t*tc 0PPc ,*jy fori fgscntial .',fe the id< Etybothr |<gffcrcnt fftm to r to far as ryrr way Trichlc trtrachlor m May until No' ring 8 gr TABLE 4 Condition's Maintained during Inhalation op Low Concentrations op Thru : CoiirOO.VDS DURING 8-IIoUR INSTEAD OF 10-IfOCR PERIODS to the f ' end this ' throughc MATERIAL TCUP. AY. CONCENTBATtOM Of AU IN box TOTAL EXPOSURE ;V inimals I which di 8C. mf./cu, m. Penta and hexnchlornaphthalcnes......... 149-193 1.44 90% penta and hexachloruaphthatenea plus 10% chlorinated diphenyl........... 150-197 1.66 Chlorinated diphenyl............................... 153-174 0.93 ranft High 2.58 Low 0.42 High 3.30 Low 0.56 High 3.23 Low 0.03 iaun 920 912 920 . fas of v wasting i T death w: . ' ipiratory tion to t. stoh fight ch of great ? cate that compounds more highly chlorinated than trichlornaphthalene are capable of causing liver injury when inhaled steadily in quite low concentrations. It is an extraordinary thing that even the most searching examination fails to show injury in any other region. It is not easy to grade the toxicity of the different compounds tested, but the chlorinated diphenyl is certainly capable of doing harm in very low concentrations and is probably the 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 addedj being reduced as the number of rati, lessened during the feeding period. The experiments were designed to pvt an idea as to the possible toxicity of the compounds selected and, if toxicity was observed, some idea as to the site or sites of damage. _ The experiments were successful . Tdra i'i: Feeding Ak, dosage of Iff. All the ai ;..iv were eitl 29,1930. i.^cT At au logically affected. ing, hyy sons a there ne was a tr most dangerous. Industrial experi ence combined with these experiments make it appear probable that work both respects, and indeed one anticipate that future appraisals of tte^j possible toxicity of chlorinated hydroxy Penta Feeding dosage : life WATER PCB-00049362 ^ ^ , ^ ^ ^ ^ ^ ^ " '" ' * ' ''^' *'^^y'"*V/ *y" *',,-y`*S>vx.\ ^.^T, i P*` .*"w-?l EFFECTS OF CHLOIUN may often be made by simple is* and do not require the elabogppsratus and the expense necesfor inhalation experiments. The reason for this opinion resides gf* identity of the lesions produced loth methods, and the fact that the fc compounds so far studied to arrange themselves identically mm2rf*r u toxicity is concerned whichway they are administered. hr.Trichhrnaphlhalcne plus traces of 'j^Atnrnnphthalene.--Feeding began fli.May 4, 1936 and continued |*Wti November 2,1936. In the begin- tjcg3gm. of this mixture were added ti |lw food for 10 rats each day, igoi (his concentration was maintained throughout the experiment. All the >s were killed except the last f died on Nov. 2. There was no if weight and no appearance of .^(%rting illness of any sort. The single > Ath was due to some variety of rc.* J$fctory infection whirl) had no rela" fa to the material inhaled. ological examination showed changes in the liver but nothing t*?at significance. Tdra and pentachlornaphthalcncs.-- began on June 29, 1936. A of 0.5 gm. daily was employed. I the animals sickened gradually and iwsr* *ther killed or died by August ^11,1930. jfc? autopsy both grossly and histo< 5*TM^ l`vcr was the single organ ^ ^10 l'vpr cells showed swell}!,.-yjl h^ergranulation, hyaline inclu- fas and vaeuolation. Here and * *itn<:Cr0^C cc^s were found. There '/.!^a^rcrnondus accumulation of fat. aru^ hcxachlornaphthalcncs.-- 8 began May 4, 1936, a 3 gm. ^eing used. By June 6, nine rats had died. The last one was obvi ously ill and was killed for autopsy examination. All animals lost weight from the beginning and were ill. At autopsy .the liver alone was affected, the lesions observed being similar to those that have been described for tetra and pcntaehlornaphthalenes but worse. DO per cent penta and hciachlnrnaphthalencs and 10 per cent chlorinated diphenyl.--Feeding began May 4, 1936 on a 3 gm. dosage. On May 16th feeding was stopped but all the animals went on to death, the last dying on June 8th. An autopsy the liver lesions were extremely severe and of the usual type. On account of the high toxicity of the 3 gm. dosage, four rats were given a 0.5 gm. dose every other day. Feed ing began June 24, 1936 and the last animal was killed Sept, lltli. There were no deaths but all the animals lost weight. At autopsy the liver as usual was the single organ affected, the lesions being characteristic and ex tensive. Chlorinated diphenyl. -- Feeding be gan May 4, 1936 on a 3 gm. dosage and was discontinued on May 10th. Seven of the 10 rats were dead by May 12th. The three remaining rats gained in weight but were sacrificed for autopsy purposes on July 8th. The liver changes began at once. There were no changes in other organs. A second group of 10 rats was fed a much smaller dose -0.5 gm. every other day. Feeding began May 20, 1936. The first rat died on May 29lli and four more before June. 21lh. The remaining were sacrificed. Those rats that died showed losses in weight, ' le those sacrificed had recovered WATER PCB-00049363 MM mmm m : ' Jf :ji' ;- piPlT;.- i^vki r*i* ;i *. ;'. !|p:; : '&$#:i '! iV V - : :. ff&'.'-i > KM %KI^'V'': |V-. .' '<<'? .:?' . ' It'ir-: \m,r ' " `I : .. Jliff: ' Kyf-.A ' c 29S JOURNAL OF INDUSTRIAL lIYtllDNK AND TON ICOLOG\ their initial loss in weight and were gaining. The liver lesions were similar to those found in rats fed penta and hexachlornaphthalcncs plus 10 per cent chlorinated diphenyl but not so marked. Summary of gross feeding experi ments.--Of the various materials fed rats in large doses triehlornaphthalenc plus traces of tctrachlornaphthalcnc was quite innocuous. Tetra and pentachlornaphthalenc showed definite liver damage. Penta and hexachlornaphthalenes caused a similar grade of injury. The addition of chlorinated diphenyl to penta and hexaehlornaphthalenes increased the toxicity. Chlo rinated diphenyl alone produced liver lesions but in the dosage used was less effective than when mixed with highly chlorinated naphthalenes. In no case did the compounds used produce acute yellow atrophy but the lesions ob served indicate this might be possible if one found a dosage which could act for the proper period of time. Feeding Precise Doses 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 eu. m. was first calculated and reduced to milligrams per kilo gram. The rats and rabbits received this dose each day. The compounds used were those employed in the gross feeding experiments and (lie results were essentially similar though the lesions were less severe. Subcutaneous Injections The same gum acacia suspensions were injected subcutaneously into rats . ''ojf and rabbits, the dosage being ralcy.^ra luted on the basis of 4 mgm. per cu. of air. Again similar results obtained. In all such ex|x'riment*V there must of necessity be difference*-^ in the degree of effect but invariably^ the liver was the sole organ affected^ and the lesions were those idread/? described many times. gad on mar . . (gfferent con 'rooms- it "I uinly casd.' that the air core than ( *. of these cc jgjphthftlcm 3 ionpound c Discussion These experiments leave no doubt" as to the possibility of systemic effect*! from the chlorinated naphthalenes and* chlorinated diphenyl. .\s in the cm* of the effects upon the skin, the degree^ of chlorination seems to determine the, *ft permi **ny exam ; ffents that iT^lteo great1 " ' j) a fed that been inex {yimsn exp systemic toxicity, and it is a striking; Time and thing that when trichlornaphthalcnei* ' reached systemic effects arc nevcrj| thinge the but today marked and arc. produced with tbt: greatest difficulty. It is most remark Mft. Imp enmgeme able, too, that' all the compounds': "t lydrocarb- tested attack the liver and the liverj k < (lifeguard, alone. During the past few month*! lad tetrai we have determined the organically combined chloride in the livers of i mals very severely poisoned by penta| and hcxachlornaphthalenes but havt^j found no increase over normal figure*, . though the livers, as determined histov logically, were very severely affected.;j At the present time we arc conducting^ inhalation experiments on a chlonnated diphenyl containing 55 per ceaM of chlorine instead of Gt per cent in the case of the experiments reported^ #' ;. Cbmrrois-f /. profess if' tiline. (163-4). AN profess ' lea de S35 (19 ,,ftnrn, F. I ''eertain Ji-J: ' liter. in this paper and on a compound with; a chlorine content between Iri letra-hlon-aplilhalene. We arc also ..JS * liTMAHN, Afhoil id, i,. determining the degree to which tb , diet may increase or decrease toxicity-,, this being suggested by similar wod^ upon carbon tetrachloride. * In the basis of these experiment*. +y: WATER PCB-00049364 *tA 0,*a- 71 effects of chlorinated hydrocaiihoxs 299 many determinations of compounds in the air of work- it appears safe and it is cer$5?easily attained, to ventilate sd * jUjje air breathed does not contain fi'Umn 0.5 mgm. per cu. m. of any 8 compounds above trichlor- '^fcthalene. In the case of the latter ^jgjjpound concentrations of 10.0 mgm. permissible. We know from examinations in many different that such concentrations have &f greatly exceeded during the past [?,}Jyears, and we arc conscious of the (hat our rat exposures have rcYtaca inexorably constant whereas exposure is never so ordered, ^xiae and careful observation may `jjdange these opinions as to standards, ;V(t today we arc convinced they are 'iHU. Impregnating tanks and other g^'Orugements utilizing the chlorinated ; kylrocarbons are easy to hood and to (Jtfcfuard. Compared with benzene, I.tetraethyl and many other corn- pounds, those substances are very little toxic and operations employing them can easily bo safeguarded. It may be argued that where possible trichlornaphthalenc 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 r^Akreis-SoFFlT: Etude sur l'intoxication jvjf*Ti(iionnelle par le trichloronaph^tillae. Ann. de mfd. legale, li, 422 Abstr. of paper by Tocn.uxE, xnd M/;.vtbel, B.: Dermatoses Sji'jkj^h'sionnelles par la nnplitaline et deriv6s. Prat. mfd. franc-. IS, gSTttS (1934). P. B., axd Jarvik. N. E.: Action of ^f f^tain chlorinnted naphthalenes mi the Si^.'Bnr, Proc. Sue. Exper. Bi|. ,t Med.. . u> H8 (19.10). " hurz<''1 I-cluliueli tier it' u "'heits- und Gcu'crhehygicno. S. Ilir- M|. Leipzig, 1919 (p. 251). Mittelstadt, 0.: GcwcrhcsrhiidiRungcn dureh Itaftax (Trichlomaplithalin). Inaug. dissert., Jena, 1935. Tf-boens, B. D.: Portable eombustion ap paratus for field determinations of chlorinated hydrocarbons. This J., 19, 20-1 (1937). Tei.ex v, J,.: Die Pernakrniikhrit (f'lilnrarne). Klin. Wrhnschr., S, 897 (1927). ToVIIAINE, A.. Sot.ENTE, M KN fit'IIKI.. II., AM) Acinus': ('i II<|I|.-U t ti--< I im I-re rat tie ili'rniiititt'S par tr i<" h I r< i n :t | *11 t.-i I i 11 <. Hull. Sue. dermal. et syph.. U, 2fi.i (1931). M 'J i M 904329 WATER PCB-00049365 JOURNAL OF INDUSTRIAL HYGIK.NK AND TOXICOI.OGV rd. I*. " Discussion Dr. Cecil K. Drinker: We have had quite a long morning, but since Dr. von Octtingen has to leave, 1 am going to ask him mincline them to. First of all shall ujl Dr. Sayers if he will open the diacujflw^.t for us. to say a word. Dn. R. It. SAVF.ns (Chief, Division tCDr. W. F. von Oettinoen (Director,. industrial Hygiene, National Institute Haskell Laboratory of Industrial Toxieol- Health, U. S. Public Health Service, gy, Wilmington, Delaware): I wish to con ington, D. C.): Dr. Drinker, Ladies sail gratulate Dr. Drinker and his group on the Gen tlcmcn: It gave me a great deal of ple^i very interesting and excellent work on the ure to have the opportunity to listen totV&j subject. I also wish to congratulate the excellentt annnrdl iinntlnerre/iastllinngi. Sdisiac-u.siss,io:.n. 104.'III! Halowax Corporation on the fact that they presentations made this morning. Dj didn'tspare any effort to elucidate, the prob Drinker, and I might add, the members lem so that the dangers which apparently the Halowax Corporation, have discussed are connected with the use of this material this matter with us, as well as the can be controlled. facturcrs of the diphenyls. I personally believe that there is no toxio We have been doing some work but not material which cannot be used safely if it is nearly ns extensive as that carried on here. handled properly, fn order to handle such The work that we have heen doing seems la : materials properly during the differen t oper confirm the work that Dr. Drinker has car.^ ations it is absolutely essential to be famil riedon. [ think there arc certain parta of It iar with the toxicity and especially with the that we con very well keep in mind. ' mechanism of the action. Since there is no We are dealing with toxic substances, but animal which corresponds in all its physio we arc dealing with toxic substances each; logical characteristics to the human being and every day in industry--harmful sub* it is important that such compounds be stances, hazardous substances. That tbetf studied with different species of animals so can bo controlled is well known, no matter'.y thatonecan get a cross-section of the poten what they are, and that we can use them and ' tial dangers. use them in a safe manner. Dr. Drinks, In addition, this fact illustrates the im has called your attention to the fact portance of the pre-employment and peri this apparently has been done and can be odical examination of workers in such work. done in any of the plants where halowax t As was pointed out by Dr. Drinker, there used. I have information from one or tv* are individuals who are apparently more of the other men who are in the audience susceptible to certain toxic agents than that in plants where damage has been others. On the other hand, we have to try --skin damage ami apparently liver damage to detect the very first signs of incipient to some of the workers--the manufacturer* poisoning in order to prevent more serious have since corrected the conditions and ap damage. In .the present instance it is very parently have adequate engineering coo*X| difficult to find these very first symptoms trol supplemented with adequate medical because there are no adequate methods, but control. 1 trust that in time the scientific profession will supply the medical profession with ndequate methods which will allow the After all, the proof of the pudding i is mthe entiog. If the mnn docs not get thedta-.jj case your engineering control is successful. < physician to determine incipient damage of If lie docs get the disease, no matter "hat the organ before serious clinical symptoms you linve done in the wnv of engineering, -L become manifest. you Imvcn't been successful. We must g Thank you. hand in hand. Neither profession alone Afternoon Session can be successful. Wc have got to wor together whether wc like it or not. I b*P" Dr. Cecil K. Drinker: In this discus pen to like it. sion I will call on one or two individuals and There is one other thing. As far as I shall expect others to apeak as their notes rials are concerned 1 think we ought to h* H (ttafuiiy *daptd it A110' viooi to fta flam ^psoxiir ; mf pi)r Mtex i"; It might wtniquii |*ppenec with this ttectric xmoe on tttdwM < ^oximat to 1 1 tee bottom 0 Inspector bldecaptba fir k fiine- h Here 3 Sow we doe to t . evaluate ua inf' ot just Ismmabi ehlorina t ~d*o inc. awea, think tha bare the; control l '* can. . Perbap tre better present ti better. I guhmarmi Son-flsmi ei their e Dr. Ci you care Dr. A of Occuj arctic ut Coon,); anythin g thia mat i&h m re"ivc .A : ,, 904330 WATER PCB-00049366 . rl effects of chlorinated hydrocarbons 301 v^^ough to use every one of them suc&5jj* If th"is material is parti`cu'larl' y for a certain purpose we should use ^^Jliiotber material that was used pre^ this for insulation purposes, which ^fl.mmable. caused a disaster in which JSjjfnjalely 167 men lost their lives. I ^VjipproximaMly 167 because they were just sure whether it was 167 or 168. itht have been one or two more but they j quite sure that 167 lost their lives. It Lfpeaed when they had insulated a cable ffth this material. They had an armored " d cable. It was covered with lead a__ jmi the outside. It was 1200 feet long ' 'tsfna being lowered into a mine shaft ap- pnsisutely 3000 feet deep. It was lashed ,V III iteel rope. It slipped and fell to the .:^h*ttom of the shaft. When the foreman was tupectiog it he set it on fire with his carJW* tap-lamp. The carbon monoxide from fain killed those men that were in that -Safe*. Many of course escaped. ./Birt we have one hazard, a fire hazard, r we have another one, a health hazard to the toxic materials. We have to te them. Certain of these materials, :1(B informed, are also flammable. I am i Just sure how flammable they are but Mobility probably decreases as your etfirlnation increases. But your toxicity increases as your chlorination in*, according to Dr. Drinker, and I : that checks with other findings. We -these hazards to balance but we can them, I feel quite confident that .tan. i Perhaps we can find other substances that l better even than this material. At the i E?*0* *`me * am advised that we have no * twter. j am advised that in ships, such as it is quite important to have a ^ w^flanunable substance for the insulation electrical wire, . -JP*- DecieK. Drinker: Dr. Gray, would Jy . e4fe to >ay a word? ;rj; ^ el ^LnEnT Obat (Director, Bureau t*~~ ...... cuPational Diseases, State of ConJ Department of Health, Hartford, *ayth " ^ don't think there is r,:.gc I can say except that wc used us. material in Connecticut and we had a number of so-called cases. All I can say is a confession of ignorance on our part at that time and I was very glad to see that your digging into the literature as thoroughly ns you have hasn't elicited any further infor mation than we were able to get, basically. About all we could find was about the two cats that our friend, Lehmann, experi mented with. We got in touch with him and he confessed that the amount that he had given the cats and his method of determin ing it were probably subject to very serious scientific criticism, and we agreed with him on that point. We felt, and I am very glad that it is what you feel as a result of your experiments, that if we put in an efficient ventilation sys tem sufficient to prevent the dermatitis, we probably wouldn't have liver damage. That is what we did entirely empirically. I think that is about all I have to say. I have been delighted to be here and to have as many members of my staff here as I could jack out of the office. We have been de lighted to listen to the discussion. Dr, Cecil K. Drinker: May we now make the discussion general and those who have questions please volunteer. Mr. Manfred Bowditch (Director, Division of Occupational Hygiene, Massa chusetts Department of Labor and Indus tries, Boston, Mass.): I would like to second very strongly what Dr. Sayers has said with regard to the approach to this problem in proper control rather than by prohibition, which seems to me wholly unnecessary not only in this cose hut in the case of other toxic substances with which wc have to deal. The problem of proper ventilation seems to me relatively simple from what I have heard of the situation thus far. The problem of maintaining tlmt ventilation properly does not seem to me quite so simple. I think it is going to be quite necessary that there should be a very adequate inspection of the plants using the materials and I ran assure you that that will he the ease here in Massachusetts. When this trouble first broke in this state a little over a year ago wc issued a quite strongly worded warning letter to nil plants using these substances and it has all along JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY {V been my plan to follow that up with a fur ther letter bringing the situation as we now know it, as a result of Dr. Drinker's work, to the attention of users in this state. In that letter we shall unquestionably advo cate the concentrations that Dr. Drinker has suggested this morning. One point that I think is worth comment ing on in that connection is the question of identification of the substances. It is ex tremely important from the state adminis trative point of view that employers using these substances should know what they are using. They are identified at present only by numbers. If we list those numbers in a warning letter which we send out there are likely to be changes in those numbers. The Halowax Corporation is a progressive con cern and it is going to be putting out bigger and better halowaxcs 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 say anything about that. Mr. Sandford Brown (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 chemical manufacturing company today you will find anything from one to a thousand different new chemical products which have not yet been put on the market. Some of those may or may not be toxic. The prob.lem so far as the chemical manu facturer is concerned is a question of timing. You have heard this excellent presentation given this morning by the Drinker brothers as to the work that they have done. here. Should you take a product of which you have developed, say, 5 or 10 cm. and spend $50,000 on research to determine w lielher or not it is toxic or should you wait until you have determined whether you have a market for it? If you nre producing only one hundred substances a year you can see that that would run into boxcar numbers in the way of dollars and cents before you over on' any. That is the problem we have hajjj this case. It has been on the market! 25 years. Until within the past 4 or 5*(Jj there has never been any intimation thattf would cause any systemic effects. sands and thousands of workmen have di with millions and millions of pounds of tain of these materials, particularly the chlomaphthnlenes. Then we come to higher stages, combined with chlorinate^ diphenyl and other products, and suddenly this problem is presented to us. ^ We had asked various authorities b.; tercsted in public health, going back overt period of 15 to 20 years, to investigate but there wasn't much enthusiasm for Mr. Bowditch suggested that we take it with the Drinker brothers at this instlt*-' tion, which wc did. You know the restdfc of that work. Now so far as these changes are cerned, they are beyond our control to I certain extent. We will manufacture product--let's call it 1231. It has certaW chemical and physical characteristics. lt-j is supplied to a cable manufacturer. It if composed of certain constituents. T! may be some tetrachlornaphthalene, tr{| chlornaphthalene, paraffin, a little piteh or bitumen, and possibly some chlorinated diphenyl. It docs & certain job but wants it to a little more plastic or he wintil its viscosity or the specific gravity changed. Possibly by a change in those constituent! of only 1 per cent wc can get that particulif property. We can't sell it to him M tf same product ao we put a new number on i Basically, however, if the variation in chlorinated naphthalene or the chlorinai diphenyl constituent hasn't changed, toxic property of that will not change. ^ When it comes to a question of cooper*!*, mg with the state authorities in that cod*, nertion, if there were some major change made in a product we would have no he*i*t tiuiey in advising them and wc would alao ml vise our customers. Virtually every cB` sumer of these mntcriuls at some time of ^ another has been given their technical or chemical designation along with their v ous properties, w hether they he physic* * chemical. . Those arc some of the practical probl**; |lh rty* -t *aj 90433k 1A WATER PCB-00049368 EFFECTS OF CHLORINATED HYDROCARRON'S 303 v.c.til manufacturers of chemicals .^fronted today, particularly in the organic field where the dcvclop- V rapid that our sales departments xZ*t*n keep up with the research depart- :v- tf gemetimes, in knowing what they are p, R. Kaimer (Assistant to ManYork Wircworks, General Electric Co., ` Tk Pa-)-' I am certainly pleased to have opportunity to say a few- words with `Y'itfstsce to the experience we have had at York plant. I perhaps should say that la this case experience alone has been ..`gui teacher. I have lived with the *'V.*Hreoh the York with experience the men from its who went beginning. III* only 15 years ago that we had in the rMEfbborhood of 50 to 60 men afflicted with " degrees of this acne about which you know. Eight or ten of them were very ->:attrly afflicted--horrible specimens as far M their skin condition was concerned. One ixmclled and the diagnosis may have attribiSSpfrd his death to exposure to haiowax P^TtJpers but we are not sure of that. There lu atrophied condition found as a result the autopsy but we are not definitely sure it was or was not connected with his Knowing the man as I did when he employed, with the superficial examinaiCso that he had, he appeared to me very .nUl, pallid in his appearance, and I would Iff from my poor knowledge of the al make-up of the human being that presented a healthy appearance. How(*** it was only for a 6 months' period from '' tM time of his employment that he com-jkfaed of this constipated condition and we ._Mfbed that he see his home physician. It -fMdly developed to the point where he was -the hospital and in a very short time he _* - ' ^or* serious than that perhaps is the fact *( had 50 other men in very had condi(!! U ^ar M the acne was concerned. The tt&c*'on that several of our executives ; . ,M to throw it out --get it out of our They didn't want anything like ^or treating wire. Rut that was easily | * not so easily done. We might just l *( I have thrown our business to the (our and said, "We'll close up," because there was no substitute and there is none today in spite of all the efforts we have made through our own research laboratories to find 011c. Hut we did develop --and [ 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 quartz light, x-ray, mechanical removal of comedones and the treatment of pustules that de veloped in later stages, an utterly strict routine where the worst eases were adminis tered to each day for a period of 15 to 20 minutes, another group who were less seri ous three times a week, and still another group once a week, we have in this year and a half brought each and every man back to a normal skin condition. Those who were very seriously afflicted do show scars, but otherwise their skin is as healthy in appear ance as my own. I tell you we are very proud of the fact that they are still all em ployed and the amount of haiowax 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 roverse of that process, with the assurance that a shower will be taken before the street clothing is again put on, we have found no recurrence of this skin trouble. Each and every man working with haiowax products, cither from solution, from solid compounds or handling the wire insulated and treated with it, is examined twice yearly with a com plete physical examination, including blood analysis and efforts to determine any liver damage. However, there is the point which was very definitely brought out this morning. We tin not know as yet when this thing starts. I believe it would be oi great help si! )iA Jt/' 304 JOL'RN'AL OF INDUSTRIAL HYGIENE AND TOX[COLOGV ^ im'M to us all in industry if some very funda mental work was done on humans, as Dr. Jones mentioned before we came into this meeting, some control in fundamental work to determine some method whereby we may determine the inception of any liver dis order. We have had our men examined in groups three times since the trouble developed and nothing has shown up in any one man. We have learned and appreciate the fact that wo must handle hazardous materials, but we have learned how to handle them. It has been a very great experience for us and for myself, and again the best teacher. Dr. Cecil K. Drinker: Can you recol lect the air concentration that you are main taining now with your present ventilating equipment? Mr. F. R. ICaiuer: We have had two examinations made of the air by Mr. Wil liam F. Hempcrly and they average from 0.2 to 0.6 mgm. per cu. m. We recently dis covered one condition which was found as the cause of a high reading in one of the examinations. The com pound is one that is 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. It is in the form of a paste, reduced with solvent to a paste form, and it was not known that it contained a chlorin ated solvent in certain percentage. We dis covered it only recently through the analy sis of a sample and we found that that was the cause of throwing the results off to a high value. It was then about 8 mgm. percu. m., I believe.' That is going to be eliminated now. That is a combination of toluene and carbon tetrachloride solvent. When that compound is exposed to the air the chlorin ated solvent odor is completely masked by the toluene. It is lost. I was able todctect it only by removing the head of the drum and immediately smelling the odor of carbon tetrachloride. As soon as that bend was removed for a period of 10 seconds the tolu ene predominated and wc hnd no knowledge of the other being in there. Mr. AnriiCR G. llr.VEn (Research Engi neer, United American Uosch Corporation, Springfield, Mass.): Do 1 understand to say that those men who were a-nffolict-ed' arc back on the same job? Mr. F. R. K.umer: They all returned fc. normal skin health, ns 1 say, and are work,-' ing on the same job. ' Dr. Cecil K. Drinker: Dr. Schwartz,' you have seen a good deal of this genera]' subject. Dr. Louts Schwartz (Medical Director Dermatoses Investigations, United Sltta Public Health Service, New York, N. Y'.,>3 I am primarily interested in dermatitis sad it was only because of my researches in that field that 1 happened to come across infor.; motion given to me by Dr. Gray that then <j1 wore some cases of yellow atrophy of tha liver attributed to halowax. I can onlf* talk from personal experience about theiUa cases. I know from what I have seen aad from what I have heard from doctors have been treating these cases that if they are treated like an ordinary acne vulgiritv and kept away from further large expoaort they all get well, with the same results at acne vulgaris. Those who have large p tulcs may have scars resulting and thoat^ who have superficial pustules or only c dones won't have any scars. As far as prevention goes, I felt even fore this investigation was undertaken that this substance, like any other poisonoa Bubstnncc, can be handled and used in in*, dustry provided proper safety precaution arc taken, and I so advocated at the meeting in Pennsylvania when this was discussed.' About ventilation and safety precau tions, I think that while wc cannot, without^ present knowledge, detect by any chemical.U,^ tests the early symptoms of intoxication^,!/* from this substance, the skin offers an easy ( way of proving whether your method ventilnlion is efficient or not, If there art any cases of acne or of this dermatitis occur* ring in n plant where haiownx or the cblono* ated naphthalene or chlorinated dipheoyi are used, then that shows that there i* * ficicnt concentration of these substances the air to cause plugging of the follicle* . to cause a skin condition. If there is cient concentration to do that there ref- 904334 WATER PCB-00049370 3253 EFFECTS OF CHLORINATED HYDROCARBONS int concentration to cause systemic - .)r.r-r in the few people who are hyper-Stlve to the action of these hydrocar- Everybody is not hypersensitive to If they were, of the thousands of 2', who have been handling these sub- ?\Jeel more would have contracted this it would have been reported ' much earlier. This material was used IA fc Germany as early as 1014 or 1915. I cannot add anything to the . methods outlined here for safety in the way H rentilation and so forth, I can say that % -:fM go into * plant and find that there is acne present among the workers with &k material you will know that there is '(^Sclent of the substance in the air to cause and consequently sufficient perhaps to k dangerous to the few people who are ftjpenensitive to its action. Dm. CecilK. Drinker: There is a prac- ^fUjtkalpoint in regard to the question of deterthese substances in air. My brother jSp&Vfdated out this morning that there are mral pieces of apparatus for doing this. It has teemed desirable to a number of the .^atea who are here that during the next cou'. pt of years, while we are in a position of laaniag, that we endeavor, if we can, to ., testae our analyses to one piece of appa- , so that at least our results will be as sparable as we can make them from place |!r".', W Place. Kf 1 don't know much about this phase of the subject: perhaps, Mr. Cook, you have ~ i idea or two about that. rrv.v. ,, ^ ` ^AaHE!( A. Cook (Chief Industrial ''^TPeniat, Bureau of Occupational Dis- ?***' l Connecticut Department of w B^lth, Hartford, Conn.). On the deter- f/'j' Nation of the halowax I wonder if it -F^ddn't be preferable to have Mr. Hem"y My discuss the method he has been using ~**uShout the country for the determina- i chlorinated naphthalenes. Cecil K. Drinker: I think so far ixiij. that is concerned it is best to leave that vdiscussiona with Mr. Ilcmpcrly and Dr. f^-fclrdt. a^erward. But the question of a /ining some uniformity of technic for ** least is, I think, a matter of gen' ' ^ flterest to us. Mn. Warren A. Cook: I am not quite sure that I have in mind exactly what you want in that regard, fn connection with sampling? Dr. Cecil K, Drinker: Yes, In con nection with the whole technic of determi'ning the material in air, length of sampling, typo of apparatus, and so forth. It has been suggested that wo endeavor to agree upon some uniform procedure for that and as figures begin to come in, as they will in the course of the next couple of years, we will at least have them on a comparable basis. Mr. Warren A. Cook: In that regard there is no question but what the determina tions and results of analyses of the concen tration of injurious materials in air, corre lated with pathological findings or freedom from pathological findings, are real factors in further substantiating toxic limits which are originally given us from animal experi mentation. In order to obtain data which are of value along that line it is desirable to know to what extent, in terms of milligrams per cubic meter, workers are exposed to in breathing any potentially injurious material. It seems to me that one of the things that should be done, whicli many of the plants and many of the organisations equipped to make determinations of injurious materials in air should do, is to make an effort to develop one group and series of results which will represent average exposures of workers to chlorinated naphthalenes. In getting that figure I think that it is of great importance that wc should consider average daily exposure. There is a tendency very often in taking samples of air to determine maximum exposures, to get the exposure over a 15 or 20 minute period when the worker may he actually tending a pot where the material is tiring used, whereas during the subsequent half hour he may be 40 or 50 feet away from that particular location. Therefore, for one thing, it seems to me it would be extremely dosirnhlc to obtain in formation in as many plants and as many locations as possible of the average expo sure, taking into consideration not only the worker's maximum exposure while actually 1 *\ . , *.s -, I liiiiliiii.. mBB .... ' ,.v\ i i ;y..x . 'j C'" ` "y H "S, i'St WATER PCB-00049371 P' * iTi f > .o'Vi '4S$ ,,iLi1'iiii H &A '04 .v.vV1 fe'j-r:-' : ip; .. Ml8-j:j{ V*: 5 ` i mjk$>: * `t/' -i1' V !**i! 0 1 y-- iV.- ! .' .' Wfy:. ' 98 |&W--- :&;, .> W to i ; i , . w St> i i> * 30G ./ockx.u. of ixocstriad hygikxk and toxicology (.sepl. tnj% at work with these materials hut also his hefore the A. I'. It. A. ill October as one of much smaller exposure and possibly even the projects which we shall carry out ^S lack of exposure as he in ay go to other parts that time. of the room or even to other departments As I have not given this ennsiderstion, I ' during the course 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 ret|f seems to be extremely desirable to have is problem here and one that deserves soa*^ concentrations of the chlorinated naph study. thalenes at certain reference points. I believe that Mr. Hemperly very carefully Dn. Cecil K. Drinker: Would it be oT' duplicated these reference points in each service to the American Public Health As*o-* of the plants where ho took his determina ciation Committee if a sub-committee from^ tions. He took the samples, I believe, at this meeting, collected perhaps by mj\ breathing level and a certain measured dis brother and those of you involved with the#W k# ! tance from the pots where the chlorinated problems, were to make a recommendatiaa^ 'll* naphthalenes were being handled, so that to the A. P. H. A. as to the things you htr4'?3 next year he could go back to those same brought up and as to suitable apparatus, locations or others could take determina and let the final statement come from th tions at those same locations, which are Association after they have considered that I definitely fixed and recorded, and learn material? whether, due perhaps to clogged pipe lines or to fans which might become loaded with Mr. Warren A. Cook: I think thatj the condensed chlorinated naphthalene, would be a splendid idea because we hart? there might be poorer ventilation than origi a bulk of information on this particular' nally designed and higher concentrations material. A number of individuals ban' M--. of the chlorinated naphthalene than origi given much thought to the development nf' nally determined. apparatus, both the combustion method p. It seems to me that it would be an ex which we have here and also the continuou^S^-ivlS'ii tremely desirable thing to have made avail record type of apparatus which Profes able for all of us who are making these Drinker mentioned this morning. I tUiin!p^;vVu..,:.,'-"=> determinations these reference points so that it is a sufficiently important proj .' that in Massachusetts and in Connecticut, that a sub-committee made up from thii 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. Curney, E. R. edge between plants. Ilayhurst, W. F. Hemperly, F. W. Sehl, and In that regard it happens that there is a A. N. Sctterlind.l committee of the American Public Health Association which is charged with the devel Mr. Hervet 0. Elkins (Chemist, DivKj HcMl IPopment of chemical methods for determina aion of Occupational Hygiene, Massacho-J tion of atmospheric contamination such as setts State Department of [,ahor and Indu*-^ that now under consideration. It seems to trios, Huston, Mass.): In connection with( me that it might lie a very desirable project what Dr. Schwarts has said, l nm not sur*-'j for that eommittee to consult with the in that I mu in complete agreement as rcgardl_ vestigator of the Hnlowax Corporation and the use of skin lesions as - warning agents- suggest to all of those w|m are doing work It is my understanding that in insulated ^ of this type, after some discussion, what wire plants the chlorinated diphenyls art. reference points could lie adopted and also very commonly compounded with the chl". what .should lie done in connection w ith get rinated naphthalenes. It is also m)' under*; ting these averuge exposures. Asa matter standing thnt thcac are more likely to c*l"*i of fact our committee will discuss that very a severe skin irritation than the stratf0^ feature ami possibly include it in our report chlorinated naphthalenes. On the ot 904336 3 WATER PCB-00049372 Kfetf 0t :sepl. /9tJ? k *" no. ?] EFFECTS OF CHLORIXATED HVDROCARnONS 307 r m one *y out n( ti"WgggjBBT^i ''v.* ^-|M J*T* *J('*ht7-fm*c ther- Drinker's work one straight chlorinated wM nearly as toxic at least would naphas the eration __M_u_n, 0f it with a small amount of chlo- J and no acne of the type described in R|>orU on the insulated wire factories. D*.R.Emmett Kelly (Monsanto ChemV. faiCo-iSt- Louis, Mo.): I can't contribute ^'mfihiflg to the laboratory studies but there quite a little human experiraentaik the last several years, especially at _ plants where we have been manufacturJk kg this chlorinated diphenyl. It has been observation that although on one oceatwT i we did have a more or less extensive fgh^Mrirtofskin eruptions which we were never gjiS&'K |b|t to attribute as to cause, whether it was ^g^.ifityin the benzene we were using or to ehlorinated diphenyl, we have never had systemic reactions at all in our men. ' have examined them very closely both frwoa what laboratory tests we thought a%?d help us and from tlic clinical viewAlso from chlorinated diphenyl ~ there have been no cases of systemic reported. I don't believe that we can transpose the laboratory results into the actual humans 1 tteut paying considerable attention to volatility of differen t substances and the they are being used. JDi. John A. Hookey (Consulting Dcr- an4 ifalogkt, Halowax Corporation, D.ctroit, ft*-): I have had considerable experience JTM the dermatological angle of this probThe experience at the Halowax plant gl^otte definitely was that the derma *** d*d increase when compounds were rather than the straight chlorinated JJJPhtfmlenea. ^ota the discussion we have heard today ^ observation Dr. Drinker made ^* chances arc that dermatological S\A|!i *m* w*^ disappear along with the other Probably true. How ever, I think that precautions, certain insurance mcas- you might say, should be taken in tnen who are going to work with products, even though we arc going to attempt to get the concentrations low. We saw this morning that the effect of these products was on the liver and that if some one working in these products 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, certainly in the preliminary medical examination of applicants for work the his tory at least should be gone into very care fully for a history of previous liver diseases. There are other things that should he taken into consideration also. One is the history of syphilis, because syphilis does have an effect on the liver. If there is any history of syphilis I don't think that that man should be hired. A Kahn test should be taken and I think that it would he a good plan to take Kalin tests on 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. Mr. F. R. Kaimer: I would like to clarify a point of Dr. Hookey's. You mentioned at the beginning of your talk that your experience in acne condition was more pronounced from the compounds of various materials with cliloronaplithnlcne than with the straight cliloronaphthalcncs. Did you mean by that, that the acne condi tion actually was more pronounced with the compounds than with the straight chloronaplitlialcnc or was that due to the fact that you were in a plant operated in a different fashion? In other words, you handled your numerous wire compounds in inure of a batch operation. That is niy understand ing from Mr. Brown. Is it a fact that the straight chloronaplithalencs are less harmful in so far ns acne is concerned or is it because of the handling of hatch compounds? Da. John A. Hookev: That is a question that would be difficult to nuswer. I based my statement on the fact that in taking a general survey ol these cases after I started working with them the men in the plant said iMIm feftv,:! Sl3lsy3Sl3ffl5sl@s? USrl fife as 13 m m ^043: jy v.X n i * j >."!,, Mil WATER PCB-00049373 JOU'.XAL OF IXIH'STIIIAL ItYOIFXF. AM) TOXICOLOGY (Sept. that they developed arne more often and more severely after they started making compounds. It may he that it was in the method of the handling. Mn. F. R. Kaimer: You say that the con dition increases with the increased chlorine content and wo are attributing the acne pri marily to the chlorine radical. If that is true, what are wo to associate insofar as these various other constituents are con cerned, such as various plasticizing agents? How much do wo know about those insofar as development of acne is concerned? Some of these compounds have a half dozen con stituents in them other than chlorodiphenyl and chloronaphthalene. We are at the present time considering the chioronaphthalenc as the basic element responsible for the acne condition which we have. \Ye know very little about what the other mate rials may or may not do. Dr. John A. Hookev: I don't know about these other materials. Perhaps Dr. Schwartz would know something more about them. Dr. Lours Schwartz: It is well known in industry that there are many compounds that cause acne. For instance, paraffin acnea and oil acncs have been known for a long time. Paraffin acncs, wax aencs, are simply a mechanical plugging of the fol licles of the skin by tile minute particles of wax that fall on the skin. I think that the acne caused by these chlorinated naph thalenes and diphenyls, because it is caused by both--I was down at the Swan Chemical Company where they make chlorinated di phenyls and they have acne there just the same as over at Wyandotte where they make the chlorinated naphthalenes--I believe that that is caused by the same thing, a blocking up of the follicles of the skin, the formation of the comcdonc and then the comcdono becomes infected and forms a pustule. They don't all pustulate because they don't nil become infected. Mnny of these men never have any pustules. They just have little white elevations on their skin. In those people who are in the arne age, the youngsters of 18, 20, 22 and 23, acne vulgaris is most apt to occur. The sebi ou.s glands are most active and they sccnn have it much more than the older people j whom the sebaceous glands are not active. We keep a clipping of all articles relattaa? to industrial dermatitis in my office and?* recently read an article in a German zine in which they report in Germany ["" similar acne condition from clilorinat phenols and chlorinated benzenes and i waxes. It seems that this acne-like con tion is not peculiar to halowax or chlori ated naphthalenes or diphenyls hut e*3 occur with any condition that blocks upt sebaceous follicles of the skin. mMt :wi.% m dip Dr. Rotal Meeker (Special Ageat^ State of Connecticut Department of Laboi Hartford, Conn.): I am full of questio As a statistician I am a little bit suspicions of averages, so I should think that we shook take maxima as well as averages in getting at the threshold dose or the dangerous1 m pregnation of the atmosphere with th poisonous compounds. I just wanted l* drop that as a hint for this committee ts consider in its work. In spite of what you said at luncheon,' Dr. Drinker, I still think it is rather impor i- tant to determine how the plugging of tbs pores actually does occur, whether they us plugged as Dr. Schwartz has suggested,^ from the particles falling on the outside the skin or whether they are plugged, many doctors have informed me, from iasidl ,; as it were. The fumes are breathed, thsjij substance gets into the blood stream thrown off through the pores of the the pores are plugged. I think it is rather important to determine that because seems to me, from the slight knowledge thai.^ I have of the industrial application of wax compounds in insulating wires, tiMy'jiir . M*. ....... ' Hiaeral Cerpon wy git y.t Up the lets me hum *1 wire, .taw tbi bet Uu Waseae We gc MM fit ftatikt the plugging of the skin, if it is just an oi ^ Sisiaia I side plugging, may take place cither fro* ^tompou handling a solid substance or from coating on the wire after it becomes col^^'',, I haven't heard anybody say anytMo||`>;;',i litrtn.il a let a eft about those Massachusetts cases of ^rj^y 1 We &i severe dermatitis and I am not so sure ......... what there was some question of liver dwo < tbeisa *u. 1 age there. Nolmily has said anything *^*^1 tequent them at all. There is no question tb W'a'.'zJ wm 904338 WATER PCB-00049374 tea VV<A.r : EFFECTS OF CHLORINATED HYDIiOCAItnONS 309 '' /* i the condition whatever tlio rnmpliea- ot--wight have been, came from handling s&ii*i21 ?thi:isn naeedcsona fginreedat area deal of course. more study, Drinker, than you and your associates been able to give it as yet. All I am f'JLtotU about is the way wc can administer r^^ketive labor laws in order to protect fSl the employer and the employee. JJpjijtened with very great interest to the 'rV-.r/^1 i&odlioos of suggested pots for the appii- raLttsn of halowax, chlorinated naphthalene I diphenyl. It seemed, to me that they ; very much to be desired. I don't see fjju (he application of the halowax com- d, If it is necessary, as I assume it is, igg ; fr trt this rather dangerous substance, can't S-Vfadone in a practically closed pot. If you ^ytase, Dr. Drinker, I wish you would ask yvjfc. Reeves of the Rockbestos Products wr LvOnporation to tell how they have handled ' H, If I am any judge of equipment and devices they have come as near to ^rV/tfialnating entirely from the atmosphere * #8 contamination from fumigated or evapo^Mttd halowax as anyone. All of the appli- iloc of halowax, either in the melting pots ':m where it la applied to the wire, is done ^Bkr hooding and with ventilating appa- and it seems to be entirely adequate. wax we had a head start as far us the ventilating system wus concerned, since ours was already installed and adaptahie to a compound with a benzene solvent rather than a melted halowax compound. In order to keep the fumes of a highly volatile sol vent under control wc did develop a prac tically complete enclosure for the container in which the compound was placed and exhausted that container in order to prevent any escape of the fumes from it. When we changed to the halowax compounds we fol lowed the same scheme of applying the compounds and used a completely enclosed pot. There is a hole in one side for the wire to go in and one on the other side for the wire to come out. There is enough exhaust suction on the enclosure to prevent any fumes from getting out of the openings where the wire enters and leaves. Of course periodically it is necessary to open the pot to replenish the compound or make adjust ments. In that case wc have the ventilat ing system interlocked with the door that the operator opens so that when lie opens it he increases the amount of air travel about ten-fold. Dn. Roval Meeker: What is the veloc ity when the door is open? . Ma. B. H. Reeves (Vice-president and f^.Otterai Manager, Rockbestos Products ((^pofstion, New Haven, Conn.): 1 will be glad to tell of our experience if it will ip the picture along. Our experience lias more or less parallel with Mr. Kaimer's >;asmuchaa we manufacture the same type i>*f fte. We have avoided the serious pic- that he ran into, probably due to the :(l - - *bst shortly after 1923 we were using jjbiuene u solvent for asphaltic materials. jW* got into anemia difficulties with ben- fumes and had to install a complete itiUting system to remove all those from the machines that applied the 111 'pounds to the wire. Following the Jlatioo of that equipment we were able substitute for benzene, so we got it the picture. are still in the same fix as every one 44 far ns finding a substitute for lialoF*** There is none that wc know of. Con- atly when we went to the use of halo- Mr. D. II. Reeves: With the door wide open, at breathing level the velocity is 200 feet. That is the linear velocity. We check that every week on every opening at every machine with a volumeter, a small instrument which is easy enough to operate and reads directly. Whenever the velocity falls below that figure the pipe connecting that machine is taken down and cleaned, bccauac there will be condensation inside the pipe to cut down the air flow and reduce the ventilation efficiency. Dn. Uovao .Meeker: What do you think of that trap device shown? Mr. B. H. Reeves: I don't know what to think of that. I don't know whether it would be practical or not. I was going to nsk l)r. Drinker whether in passing the air laden with halowax fumes through tlie boxes of ruts there was any deposit of halowax in the enclosure. * ildii'f Wmsmm SEl WATER PCB-00049375 Du. C'kcii. K. Drinker: Yes. It is detectable roadily through the outflow pipe. Mr. B. FI. Reeves: Those in the far end probably didn't get the concentration. Dn. Cecil IC. Drinker: We change the position of the boxes each dny. The ones furthest away move into the nearest posi tion, so that over n period of weeks all are exposed equully. complaints were bona lido. We had no J Acuity in handling cold wire and the m2 hud no skin trouble. Yet when they <|y the same thing with possibly the applicant ,, of heat in tunnels, ships and so forth, th ' .actually did develop trouble. We have used, of course, the icterus iodn' in following some carbon tctrachloridecM and I wondered what you have to say ab that. Is that of no value at all in the t of liver damage in this material? Dr. Emery It. H.vYuunsT (Consultant in Industrial Hygiene, State Department of Health, Columbus, Ohio): I would like to ask if it wouldn't be possible to put a cold water line around that trap and deposit it all before the air escapes from the trap. Mr. B. H. Reeves: We have tried cool ing the surface of the exhaust pipes in order to concentrate the deposit in one place and make it unnecessary to remove long lengths of the ventilating system. While wo have found a slight advantage in doing so it hasn't at all paid for the expense. It is much easier to take the piping down. Con sequently I doubt the possibility of remov ing it all by cooling the surfaces of the trap. It might be possible, by building a labyrinth of refrigerating coils, to collect it. But then you would have the problem of remov ing it from the coils after you had collected it and it would involve rather complicated procedure. Dn. B. L. Vosbcrgi! (Medical Director, General Electric Company, Schenectady, New York): We have heard about the pos sibility of preventing liver damage and skin trouble among manufacturers of wires and cables and so forth, but like the old rhyme, every dog has fleas and the fleas have fleas, we also have customers who use wires and cables in tunnels, in enclosed spaces, splic ing them together and doing all sorts of things. I am notat all certain that we know what the concentration of these chlorinated hydrocarbons is under those conditions. About the time we were having so much trouble at our York factory some of our customers began complaining. We thought wo were having a hysteria of halowax mania throughout the country. Some of their Dr. Cecil IC. Drinker: I don't think m until it gets so extreme that we know itajj way. ' Dr. B. L. VosnuRdi: I did write do*a{ few questions that came to mind. Borneo^ them have been answered and some foolish but I shall ask them anyhow. It occurred to mo that if trichlornipW thalcne has been proved to be practicaJly innocuous, isn't it a problem of reaeattk largely for the Halowax Corporation to i only that one material adopted with oil known chlorinated compounds to meet tl* requirements of customers? That is oar of the foolish ones probably, but I sbal just ask it. Furthermore, how long is it reasonable expect the liver to recover after it has beta pretty well dainngcd. I talked to you wd you said you hadn't worked that out will the animals as yet. Dr. Cecil K. Drinker: In that case n set aside a certain number of animals U recover, after knowing that a certai*, amount of damage had been done. Tbe^ wo stnrted to kill them but wc invariably ran out of rats before they ran out of lesion*. Wc don't know how long it lasts. I)n. It. I,. Vosni'imti: Have you gif** them calcium and glucose as you would wit! carbon tetrachloride? Dr. Cecil K. Drinker: Not yet, but* arc doing an experiment now with one grouP on a very high calcium diet and ano group on a calcium free diet. The w 0 question of calcium in the diet, of milk daily to these people may be wo . while. .i.a 340 77. ' WATER ; V,l If, fiO' ?l EFFECTS OF CHLORINATED HYDROCARBONS 311 g l. VosBcnmi: I just had those in mind. I would like to hear Brown would say as to the possi- 0( using only this one innocuous pglWnatcd naphthalene. . Sandford Brown: That would Uy our problem exceedingly, not only tj,a commercial standpoint but from 2^toxicity standpoint. But if we did so ^JtMak that Mr. Kaimer would be the first **/* because he wouldn't be able to get f|i liehnical effects he desires in the cable. Hi game thing applies throughout all the where we are using these higher lfcfwtnted products. ' The problem as we see it, and it is one /*kh re intend to study further (we have ~'mm program for this continuous work that [Mi be done under the diiection of the '-{Maker brothers), is to try to find a line of '/^mutation and whether or not within this (plicated chemical structure there is _ one thing that causes the trouble. If ,iV( could take hexachlornaphthalene and I per cent of some unknown constit- )**it with which we are not now familiar 4 dirainate the toxicity, that would be fefdy solution. Whether we will ever be y# to attain that I don't know. That is M of the things we have in mind. f "id before, that is one of the things which all manufacturers of these synfcde organic products are confronted at stage, either in their laboratories or in oercial developments. It is largely a on of timing as to when you should do ._A. *rk, how much you should do, and nether you know how to do it. You have **rn that first. ' ,D*.Cecu. K. Drinker: Unless there is --other important matter I will declare *0>eeting adjourned. If- R. R. Sayers: May I say a word I rcE&rd to what Dr. Hookey stated ! | P 1 *8^ R you arc going to eliminate ur workers who happen to develop syphilis during the time they arc working for you, you are probably going to lose some very important employees. It would seem that it would be worth while to give serious consideration to seeing that conditions are proper and suitable for them to continue working for you nnd that they have proper treatment. In other words, I don't believe that is a good or sufficient reason for dis charging those employees who do develop syphilis. We have not found that to be true in other places and I question whether this is one of the places. I may be in error. Mr. Sandford Brown: I want to take this occasion to express on behalf of the Halowax Corporation my thanks for the excellent cooperation wc Imve received from various state authorities and our customers as well in this investigation. I believe you have all formed the opinion, based on what you have heard this morning, that our whole motive here is to conduct this on an ethical, scientific and constructive basis. In collaboration with the Monsanto Chemical Company wc have a much more comprehensive program in view to carry on. Therefore wo want to continue that same type of cooperation. There is one thing that I want to bring up in that connection, which will have to be observed by the state authorities, when they go out to make these inspections. That is the necessity of not creating mob hysteria on the part of the workmen in the plants where these inspections are made. Mr. Hemperly has run into some very interest ing situations in the various examinations he has made. I know tlint lie would lie glad to relate them and give the benefit of liis experienee to the heads of any of these state departments who will have the direction of this work. Otherwise I can see where wc will be unable to get the full cooperation of not only the individual workmen but the plant foremen and the management, and we must have that if wc arc to get the results that we arc shooting for over (lie next sev eral months or years. This thing may con tinue, probably will continue for years.