Document bYaR3GQw8B4x44OD12GKZX3

J, THE JOURNAL OF It INDUSTRIAL HYGIENE '-Ht- AND TOXICOLOGY Xeixvz 19 SEPTEMBER, 1937 N0M3ER 7 THE PROBLEM OF POSSIBLE SYSTEMIC EFFECTS FROM . CERTAIN CHLORINATED HYDROCARBONS* ' tt.CiCTL K Drinker, Madeleine Field Warren and Granville A. iJti ' - Bennett Prptrlmml of Physiology, Harvard School of Public Health and Department of Pathology, Harvard Medical School, Boston, Mass. T". |HE use of chlorinated naphtha rapidly and thoroughly as possible.t lenes and compounds of allied In brief these cases were as follows: pharmacological possibilities is extremely wide, and with the steady jrswth of the use of electricity is cer*.Ub to expand much farther. For \ J**ra it has been known that many of .these compounds cause a troublesome and there is a large literature ;cpon this phase of the subject. Our investigations have not been concerned chloracne but with the possibility aystemic effects following ingestion inhalation of such products. In the Patient l. Male, age 21. The previous medical history of this man was in no way significant except for the fact that he had an attack of jaundice about 6 weeks priorjtn his fatal illness. Late in December, 1930, he became badly constipated and had much abdominal pain and distention. When ad mitted to the hospital he was slightly jaun diced and was evidently very ill. He was somewhat anemic and his skin, particularly upon the arms, face, chest and back, showed many pustules. He died after a brief period in the hospital, and at autopsy was found to ping of 1936, the Halowax Cori>oration, a division of the Bakclitc Cur- on, called our attention to three _ cases of jaundice in workmen jrjwng chlorinated naphthalenes and Chlorinated diphenyl, and requested the subject be investigated as Received for publication June .TO, 1937. t The Halowax Company makes many products besides chlorinated naphthalenes, and it has come to our knowledge that all of these products are indiscriminately called "halowaxes" by purchasers and users, and are lumped together aa possible causers of acne and even of svstcmic disease. Since "halowax" is merely a trade designation, care should be taken to describe compounds by their chemical names and thus avoid condemnations which are both troublesome and misleading. ' 2K3 EXHIBIT 904313 STLCOPCB4023589 ..32; ftV-j } ; i i' a'i I'".i ' . W.y- 2S4 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [Sept, ] 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. Patient S. Another young man employed with Patient 2. He became jaundiced in March, 1936, and died after an illness of 2 weeks. A careful autopsy resulted in a diagnosis of acute yellow atrophy of the liver Here again no history could be ob tained as to a precipitating cause, and there was no record of preceding attacks of jaundice. In addition to these three very re cent fatalities, we have learned of four other possible cases, none of them fatal. All of these have had jaundice and the entire group consists of iso lated individuals who have been picked out of large groups having the same exposure. In but one instance, Pa tient 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-Suflit (1934) reports on work done by Ton mine and his asso ciates (1934) who examined til) workers who had been exposed to trichlu naphthalene. Of these 13 were foun to have mild digestive complain^ anorexia, nausea and vertigo, fog? Courtois-Suffit remarks finally, r sorption is certainly possible and have for proof of it some of the i tive and general complaints wh have been due to it. But they app to be of little consequence consider the mildness of the digestive troubl^ and the absence of respiratory nomena." In Touraine's cases the exposure m* : to a trichlornaphthalcne, whereas th*j American cases of acute yellow atrophy| were exposed to compounds of higher? chlorination. Our own experiment*! indicate that trichlornaphthalenes i quire enormous dosage, far beya anything encountered in industry,: order to produce liver damage, Tetf eky (1927) reported a number of case*? of chloracne in persons exposed tOj chlorinated naphthalenes with a chlo*^ rine content ranging from 14 to 53 perj cent. He found that the lower th| chlorine content the less the acne.^ Mittelstiidt (1935) examined a number I of cases of chloracne due to trichlor-J naphthalene and reported a number vague general complaints but nothing; in the nature of serious disease. garding his animal experimentation, Lehmann (1919) reported that wiv mals fed chlorinated naphthalenes re* fused to cat after a time and that,1.' whether poisoned by inhalation or by4j feeding, at death showed "peculiar* ! lesions in the liver. Flinn and ^arv^^' (193U) gave subcutaneous injections** enormous doses of chlorinated thalenes dissolved in paraffin oil rabbits. The compounds used as follows: fj. 19. u- *1 KI'1 j \ mixture of naphthuiciu 2. A mixture of chlornaphth 3 ,v mixture of chlornaphtl ... lu addition, suN L' : p) were collected ^wbcutaneously. - None of the anil ' the sublimate from after 2 mouths wer ' tutuisdcd. The fi mals receiving (3) day and the last d Those receiving th were even more Autopsy in Hies ^,*triking changes ii^dcscrilied, entire ;cute yellow atn -- wggestivo to-cans elude that "eerta thalenes or imp them are capable trophy of the liv At the begin] Flinn and Jarvitfact that there 1 of acute yellow in men working v thalenes but giv to them. These the same as tl beginning of thi . Cue may si; ; literature u|>on - Ibcse substance ` L With the timi of unite vi fc'dJarvik (l!):t or even suggc> ^potl human lie - 1 line is e that the di-gin 904314 STLCOPCB4023590 [Sr :tt.M- ;| KI-TKCTS or ('Hl.Olt IN.VTI-II) IIVI)IU)('AllHONS 2So !(!&- ^ mixture of tri and tetrachlor- nifieant in relation to the produetion naphthaletie. of acne. In the work of Flinn and Mi* mixture' of tetra and penta- Jarvik (L93li) the cnm|x>iuids produc " chlornaphthalene. ing serious liver injury were the most, ^Tj A mixture of penta au<l ltexa- highly chlorinated of those tested, chloniaphthalcne. though the chlorine contents as given, iaddition, sublimates from (2) and by analysis vary surprisingly little. Were Collected in oil and injected 3. There are no published figuri's ^fccutaneously. . iqKm the; amounts of various chlorin &4}foneof the animals receiving (1) or ated naphthalenes in the air which will J&be sublimate from (2) died, and even produce injury of any sort, and while 2 months were quite normal when the work of Lehmann (1919) and of fjVjotopsird. The first death in tlu* atti- Flinn and Jarvik (I93(i) jHiint to the tW* receiving (3) occurred on the 12th liver as a possible site of injury this ibyand the last died on the 2(>th day. iudieation rests iqioii such extreme ifi-Xhtw? receiving the sublimate from (3) dosage as to fail to apply directly to even more severely affected. human exposure. ^.'(Autopsy in these animals revealed 1MJ kriking changes in the liver, not, tis Fxckuimkntai. Wuiik .fotfcuribed, entirely characteristic of In appraising the possible toxicity of -^rute yellow atrophy hut sufficiently any substance met in industry it is WRestive to cause the authors to rnn- first necessary to determine tin- prin 'dode that "certain chlorinated naph- cipal route of absorption. In the case ^;.lialcncs or impurities contained in of the compounds under considerat ion are capable of producing yellow there can be no doubt that inhalation y ;.itrophy of the liver in the rahhit." is their chief means of entering the At the beginning of tlicir paix-r, body. They are used hot in a great ^.^FEnn and Jarvik (1930) mention the variety of operations and volatilize in that there have heen three cases varied degree. They are often applied scu^e yellow atrophy of the liver in solution in such volatile solvents as men working with chlorinated tiaplt- carlxui tet rachloridc and toluene. The ^-ftalenes hut give no details in regard amounts reaching the air under such to them. 1 hese cases arc undoubtedly circumstances are hardly detectable. -- SamP ^ described in the It will however lie shown that- carbon ^r.*Pnning of this pap.er. tetrachloride adds |o the toxicity of may summarize the meagre the chlorinated uaphtbalenes ami allied &&S ''I1*111 ^ystemii' elTects from these substances as follows: "V.; ^ 'th the exception of tin* nieu- com|xiunds, and if there is possibility of inhaling these compound' in other parts of thi' factory then inhalation of ^ of acute yellow atrophy by Flinn carbon tetrachloride adds a decided Jar\ik fl93d) there arc no reports hazard. l"m|er such circuni'lances ,.l Sl|gges( jolts of sseitruiohuis elTect' Pon human 'beings. 1, . . 2. The|,r|e(` is evidence (Telekv, I'.I.'T i fe*c.,h4t l,f degglee of ebliiriuatio'ii is -tg- solvents such as toluene -hoidd be ll-eil. ()li-.i-1-vai hhi in a number ol plants eatl'cs ii' to feel that even though ! WJ -'If! 'm 904315 STLCOPCB4023591 } .' 1 & .; ' i'- k*jMp<>v.*d -. :] -I l!':|--I.'i fT v W. /. i. ' 2Mi .inrii.X.W. ()K IXIM STI! I.W. IIYCIKAT.' AX'D TO\[((>[.<>( IY 111? .-.? u oilsiiii ii iiinv ho i-xt fi'iiiflv diriy and can-loss, comparatively lilllr of I he~o waxes is oaten. They :irc tenacious substances, insoluble in wnter, :in<l if they not cm the hands they stick there, and nre not transferred to the food. Skin absorption is tin; third possible means of entering the body. It- may occur but at best must lie slight when compared to the steady inhalation of finely divided or gaseous material in the air. lion. TThliecvy 1th11riv\(e upon a <Iii-( Vorv, similar to man, and in t lie ease of t|,,^ chlorinated compounds it is possible I that diet may be very significant. Finally, their normal characteristic,` have been described so well as to make the detection of abnormalities both, easy and certain. Mclhixl of exposure. --The inhalation experiments were carried out in fnur large air-tight wooden boxes, each capable of holding ten rat cages, siw' IsraiMW K in. 1. |- runt view and inflow end of two hoses with rat rages in plan- and doors Inhalation experiments are then the most important sources of informal ion, but to tbcm we have added a cerium number of observations upon ingestion and subcutaneous injection of various compounds. /ohobilotti I'.XjH ilint ills .1 nnimlx. While rat' have been employed throughout. 'I hi-v permit 11 ii- Use of a large number of animal' in a cola I i\ e|v -mall inhalation iii'lalla- ' -2" x 22" x I I", in two tiers of five cages each. When the experiment was not in progress the doors were o|>cne<l wide and the cages kept in place (figure 1). Al tile renter ot one end id eai Jl IlX ilir inflow mil nir \v;is inirmlurt'il f 1 inmi^Ji :i |ifh* 7 iurlir^ in i|i:iin<*trr (figure 'Jl. lm\ \\;is uitli ;tn if111 i\ nlu:il v;irinIil |n trie lilnucr ultirh lili*w tin* :iir llvmiiph 'o\rr:il li i i ut -iin'ti jiijH* lti'lfirc' fiitrr- ^ : lit ;ng (tie end ol lli nietcr a> l'1:'*'*"*1 " the llmv ,,f ;llr 1,1 *' could he adiusled a from a calibrate deflector placed at . pipe into the box 5re a uniform / stream of air to tie At the opposite < outflow eiid -- tIn nas exhausted thr fitted with a damp a large central exl Alxuit 4 inches f the 7-inch pipe inti of the substance.' ihiccd into the i daily designed (figure 4), 7] inel diameter of 1* in hold the heated \ were made with a that extended to top of the (lask \\ 'this fitted a sbor length. This -|,n into a large ntblutiglitly into a hole pipe on the under flask in lorn was heater made to below the side ar top. Rubber tu dde arm with a i voir and a gentle through the me! motion and assur Into each tta^k \va ceiiligrade iliern kept in pirns- and t'me aliuvi- tin " hieli it |*;i--I i< Approximately chlorinated naphi sup? 904316 STLCOPCB4023592 1' misgsk *l. is. " ` I.!' 'Is <)! ('111.( >1! IN ATKI) IIV DIM)( All IK i\S 2N7 L in* die (III I of tin' hoX. Aii orifice eldoriliated diphenyl were plaeeil in I he meter was :< line, :i mi I but tom of each flask and inched ill the : the flow of electric heater. 1'resli samples were toiild be adjusted and read ofl directly used every other day, but it was often front a calibration curve. A vane found necessary to add 2d gm. of now .;(Jfflcctor placed at the entrance of the material even after one run since so RfTpipc into the box was adjusted to as much had sublimed. Whatever the ' <wn? a uniform 'distribution of the ease, the collected sublimate was rtreant of air to the two-tiers of eases. At the opposite end of the box--the outflow end--the air from each box *aa exhausted through a 7-ineh pi|ie fitted with a damper and connected to a large central exhaust fan (figure .1). About 4 inches from the entrance of the 7-inch pipe into the box, the fumes of the substances listed were intro duced into the inflowing air. Spe cially designed pyrex glass flasks (figure 4), 7J inches long and with a diameter of 14 inches,, were used to n hold the heated waxes. These flasks were made with a side arm and tube that extended to the bottom. The ji top of the flask was ground, and into this fitted a short tube 14 inches in lensth. This short tube was inserted into a large rubber stop|>cr that fitted tightly into a hole cut out of the 7-inch pipe on the under side (figure 2). The fa-di in turn was placed in an electric heater made to cover it eompleiely below the side arm and ground glass Inp- Rubber tubing connected the n<le arm with a compressed air reserv'r nnd a gentle stream of air blown through tIn* niched wax kept it in I'm. 2. Kleetrie licalcr fur maintaining chlorinated compounds at a constant, tem perature in place at inltmv end of Imx. niotiou and assured uniform healing. always removed from tin- upper part, Into each flask was inserted a long stem of I be lla'k and a clean lop ii-etl each ^ntigrade thermometer which was day. No 'ample was ever used for m fPt in place and could be read at any ,lme above the 7-ineh pipe through 'hirh it pns~ei|-(figure 2j. Approximately ltd gm. of pulverized f ^or'iiated naphthalenes or 2d gm. ol more than two rmi'. The Mask phi' the ft ml fill ' was on re- fully weighed at the beginning of the rim and at the end, and I he lo-- in weight Used to ealeolale (In- :i \ erage 1 'll ' i-I 1 14 90s & ...... STLCOPCB4023593 I'm:. I. I'vri-N tins* ll:i<k uniform as |>ossilile usually I'(.`tween llio and IT") c.f.m. In tin* first j;rnup (>f experiments the *5? following substances were tested: '(3 1. A mixture of triehlurnaphthaIcncs plus :t truce of tetraehlornnptliuleiti*. Chlorine euutcnt -If).!) per cent. 2. A mixture of pentu and liexa- rhlnrn.upht halenes. ("lilorine jsjy ftaU tnd hexac 10% penta and Woe* plus 10% 1 ^CUorinated dip eontent 02.li |>er ecu:. d. A mixture of 00 per relit I>ellta aud liexaelilornaphl hulcliei plus 10 percent relined elilorillaled diphenyl. ('lilorine coiltent Od.O per eel -t. Chlorinaled diphenyl. Chlorine eonl ('lit lio.O per cent. The compounds were selected as rc|>~ re-eulinjx a eeilaiu ran^e in ehlorinaI Mu '0:11 :dso IiceaU'C ol t heir indiel rial i 1111inil . In each in-lme'e Ml aiilxpo'i d, 10 rat - heina placed m e: TlieV Were fed l'ltrill& period wc the affei VV. ,troup 3 F'yi; exposure exami ii.Ii.e.'.Tbe av .-.f: -.16 hours jjjfc! a Each mo teased, ; ^'.00 p.n f Weighed, yC \. fonnity n>' \ lifted 1 STLCOPCB4023594 aii. 71 EFFECTS OF CHLORINATED HYDROCARBONS 2S9 v` Chow supplemented by lettuce, wax concentrations were somewhat -Wi, milk and cod liver oil. higher at the inflow end of the boxes. first group of experiments was Preliminary runs showed that once "jruri on July 1, 1936- and the last ' properly adjusted, wax concentrations -'"gpgRire to number 2 (penta and hexa- in the air remained very uniform from '^tyomaphthalenes) was on November day to day, but to insure absolute - jjth. The exposure to the other three safety readings of temperature, air spounds ceased upon November flow, etc. were made every night be ,'j^ On October 15th reprcscnta- tween 10:00 and 12:00 p.m. as well animals were taken out of expo- as on starting and stopping. At dif iRrt from groups 1, 2, and 4 and were ferent times during the course of the r-USfd after 2 months on December experiment tests for free chloride were \ in order to see whether this clear made but were uniformly negative and TABLE 1 Cunmoxs Maintained in Inhalation Experiment from J uly I to November 16 and IS ' UATCalAL CRU>* RISC CO.YTK.YT TEUr. AY. CONCENTRATION or AIR I.M BOX TOTAL tx- POCKC AY. DAlLT EX* TOBURE 7, c. mf./cu. m. Aourt THeUomaphthaIen.es plus traces of tatnchlornaphthalene................... 49.9 150-1C0 1.31 High 2 60 Low 0.10 1S9C 16 JmU lnd hexachlornaphthalenes.... 62.6 160-170 1.16 High 2.19 1SG4 Low 0 51 16 penta and hexachlornnphthahoeaplua 10% chlorinated diphenyl. 63.0 105-175 1 37 High 3 17 Low 0 64 1S9G 1G ^Marinated diphenyl......................... 65.0 165-175 0.57 High 1.19 1S9C Low 0 23 1G jj^ptrfcd would bring about recovery in affected livers. Animals from ilBop 3 were similarly removed from on October 4th and killed -^^^mation on December 4th. average length of ox)>osurc was py ~Ur3 daily for G days a week. > Corning at about 9:00 exposure aRd between this time and ^P,rn- the rats were cleaned, fed, r`' C^C` or<^cr to secure uniexPsurc the cages were -- on a regular schedule, since showed that under the temiwratures used no dccomixisition occurred. Table 1 shows the temperatures 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 ehlorinntetl naph thalenes anil chlorinated diphenyl in the air of workrooms.--Table 1 shows that animals have been cx|>oscd to varied concentrations of the substances under It.- 3H ft *-!* ^15};; fi'lL jte't : u N I* : i;V{ J <J f\ L |. A,M` |'. 290 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [Sept. r'" *L 13, no- tost. The concentrations employed may bo regarded as fairly reprosentative 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 healed mtrn in an electrically healed qua^l; tube and the diluent pas scrubbed a column of glass beads moistened sodium carbonate containing a tracer ^ sodium sulfite. The beads are thiL washed down anil the chloride deter. jQjjjewhat febbens's devices ai Tn both Abated'h * and ' fodium ct SUCTION In our cr apt to b Jess than quently t actually f - io small I either gn For this i use the n fa sensiti $3 as 0.1 mg It is d should e conversic pound ti mbseque ft unless th low. Ar is that t any chi determin distingui gases but m the resu puted in At thi Fig. 5. Dimensioned sketch of combustion tube and absorption apparatus. concentrations chosen for inhalation mined nepbclomctrically as silver formatio rinated : different experiments depended on these exami chloride. nations. The technic, of analysis and Tebbcns (1937) has recently de- the apparatus employed were the work scrihcd a method and apparatus which instance; repealed the amc of Frederick It. Millhiser and William should lx? equally satisfactory for this F. Ilemporly. work. In figure f> we show a dimen those uj must b The method and apparatus used for determining concenlralions of chlorin ated hydrocarbons in air were adapted from well-known procedures. The air sioned skcleli of the combustion tube and absorption apparatus as used b) us in both our laboratory and field problems. The absorption tube b The ritua Bui by 'Villa The. eqt iuction p hM1- * s',,PkjO/.O0 STLCOPCB4023596 EFFECTS OF CHLORINATED HYDROCARRONS 291 have been exposed for 1(5 hours to an atmosphere constantly impregnated with the substance under test, whereas, human exposure is usually a variable quantity, intense for a short time and then negligible. It is our opinion at the present time that the concentra tions of chlorinated hydrocarbons used in our experiments would be dangerous for workers in the case of compounds above trichlomaphthalenc in chlorina tion. Fortunately it is easy to venti late processes of manufacture which require these 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 eases of acne. Results of Inhalation Experiments. 1. Animals exposed to a mixture of trichlornaphthalencs plus small amounts of tctrachlornapthalcne. Living animals were apparently en tirely normal. Autopsies |>crformcd near the end of cx|xjsure seemed to show slight swelling of the liver, and microscopic examination occasionally showed swollen and hypcrgranular liver cells. The changes were, however, never more than slight. 2. Animals ex|)osed to a mixture of penta and hexaehlornaphthalencs. No abnormalities were observed in (he living animals. Rats were killed and autopsied every li weeks. In the first animals sacrificed liver changes were observed. These were swelling of cells, slight granulation and hvalinization. In September and October these conditions were somewhat more ad vanced, ami in November the process became stationary. There were highly fW':' * ! j . rh %>> tiy- : i'itf;! &1fbi,<f;'* to* SjfSi' fe. ftUv !L: i we: H>Mfl4,w4 if Jffiff #*.* .1 t; V-H/! , v.4 i l': ; : j H-l I; ' it- M Lb. t .' .- 8g ?r 292 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY l,S,p(. i* 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 hc.xachlornaphthalcncs plus 10 per cent refined chlorinated diphenyl. No abnormali ties were seen in the living animals. After (} 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. Sunmary 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 G weeks' exposure all the compounds with chlorination above trichlornaphthalene 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 elTect on the health of the animals. They held their weight, ate and behaved normally, being in every respect similar to the many people who have been exposed to these compounds withot^^ illness of any sort. ` The functional appraisal of the damage caused by certain chlorinate naphthalenes and by chlorinated phenyl.--There are no tests of liver' function useful in such minor degree^ of liver damage ns were produced these experiments. Indeed the anji mals resisted the injury so perfectly as to display no abnormalities except upon histological examination of f liver. The situation was perhapi similar to that met in industry, wher^' barring acne, the health of workers ufthese compounds has been good with the exception of the fact that in isov Iated instances jaundice has occurred' which upon at least three occasion' has gone on to acute yellow atrophy. During recent years this disease been seen following administration carbon tetrachloride, arsphenamina and cincophen. In the case of carbon tetrachloride it is known that a lot,' calcium diet and alcohol favor the pi duction of liver damage. For the acute yellow atrophy that occasionally complicates use of the other two drag no cause can be assigned. One ca produce acute yellow atrophy with arsphcnaminc, but somehow or other, this now and then does happen to pa*: tients under antisyphilitic treatment.-; It occurred to us that something of the same sort might be involved in thia problem. The human cases have been scattered ami few. They have been isolated instances out of large group! of healthy employees who have had equal degrees of exposure. It was our idea that perhaps many of these pcopl* got liver changes such as existed m oul rats, changes not recognizable through iny tn< action, lueh c! ..(fisturt *... a g .' thich &&T' Krrnt<o had li `aBsht: .. de< ge^icbsta ' itructi akohe " jnitioi itT - thkirii ;per ki y/ctftormE $> 0.7 ^ 10.75 c Thi v.' follow ir JW* J &t.} - 1 fe' w- STLCOPCB4023598 U& lit n0-7! effects of chlorinated hydrocarbons 293 gar means other than autopsy exami- If( upon the substratum of changes, they got an acute liver iv griurbance, acute catarrhal jaundice,' ^ a very common disease but one any of us may experience, would foK relatively innocuous disease go Jrer to acute yellow atrophy? Knowing that our inhalation rats N t*d liver changes, but changes too to cause recognizable symptoms, decided to test their resistance to p?: jofetances known to cause liver de* Kruction. Carbon tetrachloride and ifcohol were selected. Having infor.. nation that 1.0 cc. of carbon tetra. ddoride plus 1.0 cc. of ethyl alcohol ' per kilogram would kill 14 per cent of ftonnal white rats, we reduced the dose \ lo 0.75 cc. carbon tetrachloride and b 175 cc. of ethyl alcohol. ' ' This mixture was given by stomach hibe to the following groups of aniT mxl and with the results found in the fallowing tabulation. p.;' K bU fed 0.7S cc. per kgm. each of carbon tetrachloride and ethyl alcohol by elomach lube Trichlomaphlhalene plus trace of tetra'.dltnaphlhalene. Fed at 9:00 a.m., Nov. 1S36. 10 rats. No deaths. Pcnta and hexachlornaphthalencs. Fed Nov. 10, 1935. 10 rats. ' L J died Nov. 11th between 4:30 and 10:30 p.m. 1 died Nov. 12th at 3:20 p.m. !'/ 1 died Nov. !2th at 4:30 p.m. ' ' 1 died Nov. 13th between 9:30 and 11:30 a.m. - 1 died Nov. 15th between night of Nov. 14th and 12:30 p.m. Nov. 15th. 2 died Nov. 16th between 10:15 p.m. Nov. 15th and 9:00 a.m. Nov. f 16th (stiff). ^ Pr cent pcnla anti hciaehlama ph- ^ TkJ*4 Qrt<^ ^ Pfr ccn* chlorinated diphenyl, *<,*t 10:00 a.m., Nov. 10, 1936. 10 rats. 1 died Nov. 10th between 5:00 and 10:30 p.m. 5 died Nov. 11th between 4:30 and 10:30 p.m. 1 died Nov. 11th between 4:30 p.m. and 9:00 a.m. Nov. I2th. 2 died Nov. 12th about 1:00 a.m. 1 died Nov. 13th between 5:00 and 10:00 p.m. 4. Chlorinated diphenyl. Fed at 10:00 a.m., Nov. 10, 1936. 10 rats. 1 killed Nov. 10th at 10:30 p.m. (almost dead). 2 died Nov. 11th between 4:30 and 10:30 p.m. 1 died Nov. 12th before 8:30 a.m. (stiff). 1 died Nov. 13th between 9:30 and 11:00 a.m. 1 died Nov. 16th between 10:15 p.m. Nov. 15th and 9:00 a.m. Nov. lGth (stiff). Controls: Fed at 9:30 a.m., Nov. 12, 193G. 10 rats. 1 killed Nov. 13th for normal liver. This tabulation summarizes into the facts that: 1. No normal-rats were killed by carbon tetrachloride and ethyl alcohol. 2. No trichlornaphthalene 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. 3. The penta and hexachlorinatcd naphthalene, the mixture of these with 10 per cent chlorinated diphenyl, and finally the latter substance alone seem to have produced conditions lowering the resistance to an agent capable of producing serious liver disease. 4. The sole lesion produced 1)}- this test of liver function was acute yellow atrophy usually accompanied by jaundice. This test of liver function was ac complished with a substance which itself is an organic chloride and curi ously enough it is the only substance we were able to find that was effective. tSIi-L- &- v - S<*u;*. ft? v P' ! ' MBM *v.* . fe L--_2 : RMs *.1j- : i ^[iS1**'4..1:: . ; ^ * rllP''' ft' rjb;- #4 31? r' '! SfS:; ^-T;[ m/- $r ,r4-!^ * M;:| .#.t;! ; *yi i -r*>6v.y.*.?'*; SSB}6 294 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY {Scpi t&m V2: In animals with tho minor degree of signs of liver injury will be many. livrr injury which has been described months in returning to normal. we were unable to produce acute yellow- atrophy or any variety of liver effect The effect of high concentrations with arsphenamino, cincophcn, butyl trichlornaphthalenes with traces of telrafl chloride, ethylene chloride and tetra- cklornaphthalcne.--The first group ^ chlorcthylenc, but carbon tetrachlo inhalation experiments showed th ride was uniformly effective in dis this material in concentrations aver closing the existence of liver damage. ing 1.31 mgm. per cu. m. of air relatively innocuous, judged both by^ Recovery from liver damage following direct observation and by the earbogj removal from exposure.--Animals ex tetrachloride test. This is an ia-^ posed to trichlornaphthalenes plus tercsting fact since such compound*^ traces of tetrachlornaphthalene being cause acne, though less potently thaa* practically normal on removal from substances of higher chlorination.: exposure need no consideration. In In order to explore the matter further ! the case of the penta and hcxachlor- oneof the inhalation boxes was arranged TABLE 2 Conditions Maintained dciunr Inhalation of IIiciii Concentrations or TllU'ULORNArttTHALENES 1'LL'S TETIIACIILORNArilTIIALENE MATERIAL TEMP. AVo. CrOANIRCEINNTBROAXTION EXTrOOfTlCARLE XaXt.KoMiaCxlSi^Sn "C. mgm./c. u. r<in$t JUur ^ M Trichlornaplithfilcnos plus traces of 137-200 10.97 Hif-li 10.49 tetrachlornaphthalene Low 5.78 1232 18 CONOITI Pint* a N*T 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 |>entn and hexaehlorinated naphthalenes and chlorinated diphenyl and for chlorinated diphenyl alone. Apparently the changes induced in the liver cells by these substances are exceedingly persistent and one must cxjHTt that an individual showing any so that fumes from four glass contain ers were delivered to the air line instead of one. This resulted in the condition! shown in table 2. The animals sub jected to these conditions showed no clinical effects of any sort. After 1 month the liver cells were slightly swollen and over-granular and the were occasional mitotic figures. Thesej changes were similar to the eady effects of more highly chlorinated ^ compounds, and progressed only slightly during the third and fourth ^ months. When rats in this conditio11, were given carbon tetrachloride and alcohol, in some instances their livers showed massive central necrosis and 904324 r?`r m'TtSZS's STLCOPCB4023600 s .-732.SViBiAi.-' ri EFFECTS OF CHLORINATED HYDROCARBONS It, 71 ^aeibcra this did not develop. Fifty ' ftL* wvre used in this experiment mid my conclude that while the tri- r-.'O^njjphthalencs arc in no degree as '' as those of higher chlorination not entirely free from effects the liver after 35 days of freedom from inhalation. It is thus evident that penta and he.xachlornaphthalenos are markedly toxic compounds and that recovery from their effects is extremely slow. ' the liver if high enough conccnare inhaled over long periods. [&fle effects of high concentrations of ' and hexachlornaphthalcnes.-- <2^^ con be no doubt as to the dam^jldone the liver by these compounds in the concentrations so far re ? juried no symptoms were caused that f^vfBold be recognized clinically and *': fcsthing approaching acute yellow 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 16-hour periods, a further TABLE 3 f?|03*smoN3 Maintained durino Inhalation of IIioii Concentrations of I'enta ft- ' ' Hexaciilor.vai'Hthalenes 'i ' MATERIAL c*'. . ftftt* and hexachlornnphthalcnes........ . TEUF. c. 137-195 AV. CONCENTRATION or aiu in uox mg./. ru. m. 8.S3 range High 14 .0 Low 5.75 cxTroOfTlCARL c AV, OAILT cxroaCKE Aourf kauri nus 16 ]iln>phy occurred except through the we of the carbon tetrachloride test. Pa December 1, 193G, 80 rats were ^thjected to the conditions sum ttJrixed in table 3. This experment mm. terminated on January 21. All of animals lost weight and appetite deaths began after 8 days of expo- Wf Fifty-five rats died, most of heavily jaundiced, 8 were killed microscopic examination, 9 were :TI3ed ^y the carbon tetrachloride test .. ^nd 8 lived through the period of ^^2?SUre. ^lc ^v< rs ^lf! animals ^or examination showed marked flf-e . S' degeneration, central in type ^jv*Tth necrosis of liver cells. Surviving 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. Mighty 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 G 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 IG hours under the conditions set forth in table I. The carbon tetra chloride test was uniformly fatal to them and one must conclude that con- ; ;> : ' N^';,-'A sv 9.' VN STLCOPCB4023601 296 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOCY 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 be amplified upon the pathological side in a further paper by Dr. G. A. Bennett. What has been given is, however, sufficient to indi men never inhale enough of any these substances to get acute yellowug; atrophy. They may, however, acquit a substratum of liver damage u ^ which acute yellow atrophy may velop. Experience in a number plants has shown how easy it is reduce concentrations of these e pounds practically to the vanis! point, and every effort should be mad*J to attain such conditions. Gross Feeding Experiments The various compounds used wet^ ground as finely as possible and mixed* with a standard balanced ration fotj*j TABLE 4 1 Conditions Maintained dorino Inhalation op Low Concentrations op Thru COMTOONDS DURING 8-IIoUR INSTEAD OP lG-IIOCR PERIODS MATERIAL TtUP. AT. CONCENTRATION 0^ AIR IN BOX TOTAL at. EXPOSCRE c. mg.feu. m. Penta and hexachlornaphthalenes......... 149-193 1.44 90% penta and hexachlornaphthalenes plus 10% chlorinated diphenyl.......... 150-197 1.66 Chlorinated diphenyl.............................. 153-174 0.93 rang* High 2.58 Low 0.42 High 3.30 Low 0.56 High 3.23 Low 0.03 hlMTl 920 912 920 8 ^8 8 cate that compounds more highly chlorinated than trichlornaphthalenc are capable of causing liver injury when inhaled steadily in quite low concentrations. It is an extraordinary thing that even the most searching examination fails to show injury in any other region. It is not easy to grade the toxicity of the different compounds tested, but the chlorinated diphenyl is certainly capable of doing harm in very low concentrations and is probably the most dangerous. Industrial experi ence combined with these experiments make it appear probable that work- the white rat. The food was in a single container, at which the animals in a cage had an equal chance, the amount of the compounds added being reduced as the number of rat*: lessened during the feeding period. The experiments were designed to an idea as to the possible toxicity the compounds .selected and, if toxicity ^ was observed, .some idea as to the site or sites of damage. . `1$, Si. The experiments were successful 111 jail! both respects, and indeed one rnaj anticipate that future appraisals possible toxicity of chlorinated hydrov.^*~ j STLCOPCB4023602 71 effects of chlorinated kydrocarrons 207 ^may often be made by simple and do not require the elabo- jppsratus and the expense neccsfor inhalation experiments. ThehjT'hj reason for this opinion resides [Vibe identity of the lesions produced i" jjgtlj methods, and the fact that the compounds so far studied [into arrange themselves identically `ii'far as toxicity is concerned which- *ay they arc administered. ''.r.TricMornaphlhalcne plus traces of ''fcbaddornaphthalene.--Feeding began i'JJay 4, 1936 and continued Hgrfg November 2,1936. In the beginf.*tg3gm. of this mixture were added the food for 10 rats each day, i&iod this concentration was maintained *7t&fwighout the experiment. All the ' Js were killed except the last fcdied on Nov. 2. There was no fof weight and no appearance of A-vwting illness of any sort. The single v drath was due to some variety of re? tffcitory infection which had no rela- ten to the material inhaled. tological examination showed rjfifht changes in the liver but nothing l.jd p?at significance. 0i~Tdra and penlachlornaphthalcncs.-- :Jfe*duig began on June 29, 1936. A of 0.5 gm. daily was employed, the animals sickened gradually and _^in either killed or died by August jffc, 1Q36. V'-M autopsy both grossly and histo"J^dly the liver was the single organ The liver cells showed swellbypcrgranulation, hyaline inclu- and vacuolation. Here anti ^ '*>frtnccrotic cells were found. There ./V*4 tremendous accumulation of fat. an^ hcxochlornnphthalcncs.-- .^,<ding began May 4, 1936, a 3 gm. being 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 pcntachlornaphthalencs but worse. 90 per cent penta and hcjrachlornaphthalcnes 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. 11th. 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 liegau May 20, 1936. The first rat died on May 29lh and four more before June 21lh. The remaining were sacrificed. Those rats that died showed losses in weight, while those sacrificed had recovered Hi-.;. 'I ?)? ! ;."v i |V* 'u.< . ' ; Jp' !S?V ; Pill: IlfIt:' ;i. .. ' v-'j-T i' : . | pit-:.:' 'k' V-'- ' hi-': f JOURNAL OK INDUSTRIAL IIV ScP<- their initial loss in weight and were paining. The liver lesions were similar .w and rabbits, the dosage being ralcy.-'^ lalcd on the basis of 4 mgm. per cu. tad oa ma different co. to those found in rats fed penta and of air. Again similar results wert^. hexaehlornaphthalenes plus 10 per obtained. In all such cxjx'rimcnU^ "rooms, it ttinly cash cent chlorinated diphenyl but not so there must of necessity be difference^ ' tfcst the aii marked. * in the degree of efTcct but invariably^ pore than Summary of gross feeding experi ments.--Of the variovis materials fed rats in large doses trichlornaphthalenc the liver was the sole organ affected* and the lesions were those alread^ described many times. I,'-', d these c taphthalcn panpound plus traces of tctrachlornaphthalcnc Discussion' r' *rt pc'TM was quite innocuous. Tetra and pentachlornaphthalcnc showed definite liver damage. Penta and hcxachlornaphthalenes caused a similar grade of injury. The addition of chlorinated diphenyl to penta and hexachlornaph- These experiments leave no doubt* as to the possibility of systemic effect*'! from the chlorinated naphthalenes and* chlorinated diphenyl. As in the caae^ of the effects upon the skin, the degree^ of chlorination seems to determine tbep ... many exar, . ffents `ha j^ben great ?> j) yean, ! fort that iij.j- teen ine> JjQinan es" thalenes increased the toxicity. Chlo systemic toxicity, and it is a striking i'-S .., Time anc rinated diphenyl alone produced liver thing that when trichlornaphthaleneU H," chinge tht lesions but in the dosage used was less reached systemic effects arc neverj ' tot today effective than when mixed with highly chlorinated naphthalenes. In no case marked and are produced with tb greatest difficulty. It is most remark-,^ " nit. Im; ,. . arrangenu did the compounds used produce acute able, too, that' all the compounds'1'' St", Vydrocarb yellow atrophy but the lesions ob tested attack the liver and the liver, mfeguard served indicate this might be possible alone. During the past few months*^ '" itftd tetra if one found a dosage which could act wc have determined the organically for the proper period of time. combined chloride in the livers of 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 ou. m. was first calculated and reduced to milligrams per kilo gram. The rats and rabbits received this dose each da}', 'flic compounds used were those employed in the gross feeding experiments and the results were essentially similar though (he lesions were less severe1. Subcutaneous Injectiuns mals very severely poisoned by penli and hcxachlornaphthalcncs but havaj found no increase over normal figures, though the livers, as determined histov logically, were very severely affected.^ At the present time we arc conducting! inhalation experiments on a chlorin ated diphenyl containing 55 per cent of chlorine instead of G4 per cent in the rase of the experiments reported * in this paper and on a compound with~ a chlorine content between tri and", tel rnehlornnphl halene. W'e are also determining the degree to which tbe ^ diet may increase or decrease toxicity*- this being suggested by s.imilar ft .-raj A Ccvrroisproles: tiline. ' (IBM). a: 1 `AT profes. F:';.r The same gum acacia suspensions upon carbon tetrachloride. ^ were injected subcutaneously into rats In the basis of these experim1 STLCOPCB4023604 a. 7| effects of chlorinated hydrocarbons 299 Wtin many field determinations of compounds in the air of work - it appears safe and it is cer(flsily attained, to ventilate sd Hwthe air breathed does not contain i than 0.5 mgm. per cu. m. of any 'Jhese compounds above trichlor- ^yfcthalene. In the case of t he latter pound concentrations of 10.0 mgm. ' permissible. We know from examinations in many different rpais that such concentrations have '1B greatly exceeded during the past NJJjw3! and've arc conscious of the ivfert that our rat exposures have N'ita inexorably constant whereas > Vyun exposure is never so ordered. yte* and careful observation may these opinions as to standards, today we arc convinced they are vtj6t Impregnating tanks and other i'fiBWgements utilizing the chlorinated fc^irocarbons are easy to hood and to tJtltfuard. Compared with benzene, .tetraethyl and many other com pounds, these substances are very little toxic and operations employing them can easily be safeguarded. It may be argued that where possible trichlornaphthalcne 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 Etude sur ['intoxication ' ' i.P^Icwonnelle par le trichloronaph- Ultne. Ann. de m6d. 16Kale, ti, -122 3jjje.08M). Abstr. of paper hv Tocraise, *^0 Mntrel, B.: Dermatoses jSjji-P^fcssionncllos par la naplitaline et Ipr* derivis. Prat. mid. franc-. IS, (1934). F. B., AMD Jarvik. N. E.: Action of chlorinated naphthalenes mi tlie .'rx'nrer. Proc. gor [7.\pcr. ni<>l. ,t Med., , u> H8 (193(5). K. B.: Kur/.c-t I.chrluich dor j- Arbits- und Gcurrhi'liyciene. S. Hir=* V. l. Leipzig, 1919 (p. 251). Mittelstadt, 0.: Gewcrlicsrhadicuncen durrh Ilnftax (Trichlornapbthalin). InauR. dissert.. Jena, 1935. Tebdens, B. D.: Portable combustion ap . paratus for field determinations of chlorinated hydrocarbons. Tins J., 19, 204 (1937). Tei.ekv, I,.: Die Prriiakrankhcit (Cliloracnc). Klin. Wchnschr., S, 897 (1927). Toviiaine, A.. Soi.ente. .Mkntiiki.. II.. as'Ii A CM it in : ( impiaii tr-i|iia( re rn dr diTmatilcs par tricldormo'iphtaline. Hull. .Sue. drriuat. et sypli.. {/. 2(53 (1931). JOURNAL OF INDUSTRIAL IIYGfKNH AND TOXICOLOGY Dr. Cecil IC. Drinker: We have had quite a long morning, but since Dr. von Octtingen has to leave, [ am going to ask him to say a word. Dr. W. F. von Oettinoen (Director* Haskell Laboratory of Industrial Toxicol ogy, Wilmington, Delaware): I wish to con gratulate Dr. Drinker and his group on the very interesting and excellent work on the subject. I also wish to congratulate the Ilalmvax Corporation on the fact that they didn't spare any effort to elucidate the prob lem so that the dangers which apparently are connected with the use of this material can be controlled. I personally believe that there is no toxic material which cannot be used safely if it is handled properly, In order to handle such materials properly during the differen t oper ations it is absolutely essential to be famil iar with the toxicity and especially with the mechanism of the action. Since there is no animal which corresponds in all its physio logical characteristics to the human being it is important that such compounds be studied with different species of animals so thatonecan get across-section of the poten tial dangers. In addition, this fact illustrates the im portance of the pre-employment and peri odical examination of workers in such work. As was pointed out by Dr. Drinker, there are individuals who are apparently more susceptible to certain toxic agents than others. On the other hand, we have to try to detect the very first signs of incipient poisoning in order to prevent more serious damage. In .the present instance it is very difficult to find these very first symptoms because there are no adequate methods, but I trust that in time the scientific profession will supply the medical profession with adequate methods which will allow the physician to determine incipient damage of the organ before serious clinical symptoms become manifest. Thank you. Afternoon Scieion Ds. Cecil K. Drinker: In this discus sion I will call on one or two individuals and I shall expect others to speak as their notes for us. Dr. It. It. Sayers (Chief. Division Industrial Hygiene, National Institute J\f Health, U. S. Public Health Service, WuhJ' ington, D. C.): Dr. Drinker, Ladies uj'tgljj Gen tlcmcn: It gave me a great deal of urc to have the opportunity to listen to excellent and interesting discussion presentations made this morning, (y, Drinker, and I might add, the memberx the Halowax Corporation, have discussed this matter with us, as well as the facturcra of the diphenyls. We have been doing some work but not nearly as extensive as that carried on here.-'ira The work that we have been doing seems confirm the work that Dr. Drinker has riedon. I think there arc certain parts of 11 that ne can very well keep in mind. We arc dealing with toxic substances, but^^ we arc dealing with toxic substances esek di and every day in industry--harmful jub-^ stances, hazardous substances. Thattbe**^ can be controlled is well known, no matter1 what they arc, and that we can use them sad use them in a safe manner. Dr. Drinker^, hoa called your attention to the fact that* this apparently has been done and can b', done in any of the plants where halowax il_ used. I have information from one or t*#., of the other men who arc in the audienc*,. that in plants where damage ha3 been doat: --skin damage and apparently liver damsgt to some of the workers--the manufacturer* J have since corrected the conditions and *PV0 parcntly have adequate engineering coo*|| trol supplemented with adequate medical, control. After all, the proof of the pudding is ^S& the rating. If the man does not get the case your engineering eon trid is successfulIf he does get the disease, no mutter wht you have done in the wav of engineering' Ui'i you haven't been successful. We-must g hand in hand. Neither profession al* ran be successful. We have got to wor ^ ^ together whether we like it or not. I hap" pen to like it. There is one other thing. As far as mfe' rials are concerned I think we ought to b4 . Dr. A of Occuj fteetieut Conn,): anything this m&t 904330 .... STLCOPCB4023606 K'.i . rl EFFECTS OF CHLORIXATED HVDROCARBOX3 301 . Tnmlgh to use every one of them suc- If this matcr'a* '3 particularly for a certain purpose we should use '/^Aaother material that was used pre- 'ttj-- lo this for insulation purposes, which V^fl.mmable, caused a disaster in which Syidiimately 167 men lost their lives. I jSS^pproximately 167 because they were jwt sure whether it was 167 or 168. Lgjdght have been one or two more but they K* quite sure that 167 lost their lives. It '^ped when they had insulated a cable ik;. material. They had an armored " c cable. It was covered with lead t;tax* on the outside. It was 1200 feet long ' being lowered into a mine shaft apf'-prwumately 3000 feet deep. It was lashed V t* iteel rope. It slipped and fell to the of the shaft. When the foreman wns Jtapecting it he set it on fire with his car*"hideetp-lamp. The carbon monoxide from ..sW Ire killed those men that were in that je^H. Many of course escaped. we have one hazard, a fire hazard, ve have another one, a health hazard to the toxic materials. We have to (mhuta them. Certain of these materials, ;1 Ml Informed, are also flammable. I am yMt Just sure how flammable they are but fllBBxability probably decreases as your Ination increases. But your toxicity Increases as your chlorination ints, according to Dr. Drinker, and I that checks with other findings. We these hazards to balance but we can j*trol them. I feel quite confident that can. -A Psrhaps wc can find other substances that hW better even than this material. At the PT***0* time I am advised that we have no . f am advised that in ships, such as j^g^Woeurines, it is quite important to have a \"fn.able substance for the insulation .*theixelectrical wire. K* Drinker: Dr. Gray, would $.*** *re to Bay a word? J.^LnEI,T S. Grat (Director, Bureau . cuPational Diseases, State of Con- <y ^ ^cPartment of Health, Hartford, ^r- Drinker, I don't think there is * that I can say except that we used P^aterial in Connecticut and we had number of so-called cases. All l can say is a confession of ignorance on our part at that time and I was very glad to see that your digging into the literature as thoroughly as you have hadn'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, wc probably wouldn't have liver damage. That is what we did entirely empirically. I think that is about all I have to say. 1 have been delighted to be here and to have as many members of my staff here as 1 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 but 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 1 have heard of the situation thus far. The problem of maintaining that ventilation properly does not seem to inc quite so simple. 1 think it is going to be quite necessary that there shuuld be a very adequate inspection of the plants using the materials nnd I ran assure you that that will be the case here in Massachusetts. When this trouble first broke in this state a little over a yenr ago wc issued a quite strongly worded warning letter to nil plants using these substances and it has all along ...s...... fe. fe-'i ^:: P ! t . : 1$:.- IK- "-. Ivr-i-' -:- ii&ir ** i; * ... ifttifm- Jb*j. `p* .1 ':.- gt'K ' ' 302 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY hecn my plan to follow tli.it 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 i3 going to be putting out bigger and better halowaxes all the time. The company's cooperation in this presentinvestigation 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, N. Y): There are some aspects of this situation on which I think I can enlighten the medical and state and civic authorities, with respect to the commercial and practical aspects. If you go into the research laboratories of any large chemical manufacturing company today you will find anything from one to a thousand different new chemical products which have not yet been put on the market. Some of those may or may not be toxic. The problem so far as the chemical manu facturer is concerned is a question of timing. You have heard this excellent presentation given this morning by the Drinker brothers as to the work that they have done here. Should you take a product of which you have developed, say, 5 or 10 gin. and spend SIX),000 on research to determine w hether or not it is toxic or should you wait until you have determined whether you have a market for it? If you arc producing only one hundred substances a year you can sec that that would run into hoxcar numbers in the wav of dollars ami rents before you ever uii'r. any. That is the problem we have this case. It has been on the market f 25 years. Until within the past-t there lias never been any intimation thitt would cause any systemic effects. The*.' sands aarl thousands of workmen have with millions and millions of pounds ofc^i tain of these materials, particularly the ~ chlomaphthalenes. Then we come to til higher stages, combined with chlorinstef diphenyl and other products, and suddenly^ this problem is presented to us. " We had asked various authorities terested in public health, going back oveti" period of 15 to 20 years, to investigate but there wnsn't much enthusiasm for Mr. Bowditch suggested that we take ituj'| with the Drinker brothers at tills inst!fc*.l?flS tion, which we did. You know the results of that work. Now so far as these changes are cc*? cerned, they are beyond our control to certain extent. \Yc will manufacture l product--let's call it 123-1. It has certil*' chemical and physical characteristics. U; is supplied to a cable manufacturer. It h composed of certain constituents. T! may be some tctrachlornaphthalene, trf*, chlornaphthalene, paraffin, a little pitek or bitumen, and possibly some chlorinated diphenyl. It docs a certain job but- wants it to a little more plastic or he want*? its viscosity or the specific gravity changed.'> Possibly by a change in those constituent!* of only 1 per cent we can get that particular property. We can't sell it to him aa ` same product so we put n new number on ll^ Basically, however, if the variation in thlj chlorinated naphthalene or the ehlonniu diphenyl constituent hasn't rhanged, thM toxic property of that will not change, 's When it comes to a question ot cooperat*- ing with the state authorities in that coo*.^ ncctiim, if there were some major chsnfl^ made in a product we would have no hesi*^ tnney in advising them ami wc would si** advise our customers. V irtually every con sunier of these materials at sonic time ^ another has been given their technical or j chemical designation along with their van* ^ ous properties, whether they be physical oc chemical. Those arc some of the practical problem*jt fJ- ' IV?- V r' '1.** < 90433, STLCOPCB4023608 It, '* EFFECTS OF CHLORINATED HYDROCARBON'S 303 which manufacturers of chemicals confronted today, particularly in the orrg*!ainniicc ffiicclldd "wh,uere the develop- ,1| jfj so rapid thhat our sales departments *tren keep up with the research depart- tcsometimes, in knowing what they are ../lit-,'. . p. R. ICaimer (Assistant to Man- l iJ|f york Wireworks, General Electric Co., ^ ^r, Pa.): I am certainly pleased to have opportunity to say a few- words with frf*ftce exPcr`cncc *'e have had at TfgjYork plant. I perhaps should say that In this case experience alone has been :B4 b*t teacher. I have lived with the York with the men who went *he experience from its beginning. i'-N j It l* only 1J years ago that we had in the V' *^hborhood of 50 to 60 men afflicted with wNwriou* degrees of this acne about which you V;Hlnow. Eight or ten of them were very 5-N#rttrtly afflicted--horrible specimens as far m (heir skin condition was concerned. One m died and the diagnosis may have attrib- his death to exposure to halowax /'^npnt but-we are not sure of that. There j.'/vttu atrophied condition found as a result y.llithe autopsy but we are not definitely sure c;'6tt it was or was not connected with his Knowing the man as I did when he employed, with the superficial examina- i'. Cm that he had, he appeared to me very pallid in his appearance, and I would *ay 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 time of his employment that he com-- !^**Iaed of this constipated condition and we ^".dktied that he see his home physician. It **lddlj developed to the point where he was the hospital and in a very short time he W. r^^ore serious than that perhaps is the fact ~t*e had 50 other men in very bad condi J8 M Iar as the acne was concerned. The ?**" reaction that several of our executives 1 throw it out --get it nut of our .( J**- They didn't want anything like 3") ^or treating wire. But that was easily ^ut nt so easily done. We might just ell have thrown our business to the four 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 one. Hut we did develop--ami I was most closely associated with it--and set up a routine for bringing these men back to nor mal health conditions. A number of them were sent to Dr. John H. Stokes and to Dr. 0. H. Perry Pepper of the University of Pennsylvania Hospital, and the others to Dr. Isaac R. Pels at Johns Hopkins. Through their recommendations and studies we employed a trained nurse and two local physicians and you might say established a small hospital and its facilities at the plant. Through the application of quartz light, x-ray, mechanical removal of comedones and the treatment of pustules that de veloped in later stages, an utterly strict routine where the worst cases were adminis tered to each day for a period of 15 to 20 minutes, another group who were less seri ous three times a week, and still another group once a week, we have in this year and a half brought each and every man back to a normal skin condition. Those who were very seriously afflicted do show scars, but otherwise their skin is as healthy in appear ance as my own. I tell you we are very proud of the fact that they are still all em ployed and the amount of halowax thnt 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 halowax products, either from solution, from solid compounds or handling the wire insulated and treated with it, is examined twice yearly with a com plete physical examination, including blood analysis and efforts to determine any liver damage. However, there is the point which was very definitely brought out this morning. We do not know as yet when this thing starts. I believe it would be of great help --'<>.*riSJrri' ST m. i-t :- 1'J '] .' $*: '. Ay^ ;, .. U !' fyyi tvi: ! ?&*:&: ; Di'*,..' *; Hr*- i 5f-:- l. Stl'; f- Jttf ']-:: tii* u Jft:* y 1'1. pi- r- p!*v`: fev.l;K Fifiivi. Si'll"' *35j '**$&&* *WTJ i. 304 JOURNAL OF INDUSTRIAL HYGIF.XE AND TOXICOLOGY l 1117# 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. \Ye have had our men examined in groups three times since the trouble developed and nothing has shown up in any one man. \Ye have learned and appreciate the fact that we 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: \Ye have had two examinations made of the air by Mr. Wil liam F. Hemperly and they average from 0.2 to 0.6 mgm. per cu. m. We recently dis covered one condition which was found as the cause of a high reading in one of the examinations. The compound is one that is not manufactured by the Halowax Cor poration that is used rather infrequently, perhaps not more than 50 gallons of it in a 6 month period. It is in the form of a paste, reduced with solvent to a paste form, and it was not known that it contained a chlorin ated solvent in certain percentage. We dis covered it only recently through the analy sis of a sample and we found that that was the cause of throwing the results off to a high value. It was then about 8 mgm. per cu. m., I believe. That is going to be eliminated now. That is n combination of toluene and carbon tetrachloride solvent. When that compound is exposed to the air the chlorin ated solvent odor is completely masked by thetoluene. It is lost. I was ahle to delect it only by removing the head of the drum and immediately smelling the odor of carbon tetrachloride. As soon as that head was removed for a period of 10 seconds the tolu ene predominated and we had no knowledge of the other being in there. Mr. Arthur G. Hexer (Research Engi neer, United American Uosch Corporation, Springfield, Mass.): Do I understand^,*; to say that those men who were afflict^'^ arc back on the same job? Mr. F. R. K.uuer: They all returned le - nnrmal skin health, as 1 say, and are worfc.-?^ ing on the same job. Dr. Cecil K. Drinker: Dr. Schwartz/^ you have seen a good deal of this general" subject. , Dr. Locis Schwartz (Mediral Direeto^. Dermatoses Investigations, United SUt^*f3 Public. Health Service, New York, N.Y.Jl I am primarily interested in dermatitis us4 it was only because of my researches in tint field that I happened to come across infor-jl motion given to me by Dr. Gray that then , were some cases of yellow- atrophy of the -V liver attributed to halowax. I can onl/!fJ talk from personal experience about theski*' cases. 1 know from what I have seen oadT from what I have heard from doctors Th*2T have been treating these cases that if they are treated like an ordinary acne vulgirisv and kept away from further large exporan they all get well, with the same results acne vulgaris. Those who have large pi tules may have scars resulting and thoss, who have superficial pustules or only ci dones won't have any scars. As far aa prevention goes, I felt even b*- fore this investigation was undertaken that this substance, like any other poisonow substance, can be handled and used in in* dustry provided proper safety precautions are taken, and I so advocated at the meeting in Pennsylvania when this was discussed^ About ventilation and safety preesn* tions, I think that while we cannot, with oar present knowledge, detect by any chemical,^; tests the early symptoms of intoxicatic* from this substance, the skin offers an tuj way of proving whether your method of J ventilation is efficient or not. If there tit any cases of acne or of this dermatitis occur* ring in a plant where halowax or the chlorin ated naphthalene or chlorinated diphenj, arc used, then that shows that there ui ul-. ficicnt concentration of these substancel UJ, the air to cause plugging of the follicles on to cause a skin condition. If there is cicnt concentration to do that there m1/ Hj m. K'F 904334 STLCOPCB402S610 - ......... " ;2s5l*-N irWimMi-SB >*** . y| EFFECTS OF CHLORINATED IIVDROCAItnONS _ *L lt> ^ 30o j*f^oing in the few people who arc hyper- lesitive to the action of these hydrncar***" Everybody is not hypersensitive to Am If they were, of the thousands of Z<!pi who have been handling these subjtueee, more would have contracted this ^^o'and it would have been reported ' mUCh earlier. This material was used =H |i Germany as early as 1014 or 1915. ' While I cannot add anything to the ; ^rthods outlined here for safety in the way "iy :` ^ yentilation and so forth, I can say that jog go into a plant and find that there is [yv-?^j gene present among the workers with L:'~ &Si material you will know that there is * (efficient of the substance in the air to cause eat and consequently sufficient perhaps to he dangerous to the few people who are hypersensitive to its action. D*. Cecil K. Drinker: There is a pracpoint in regard to the question of deter- SS^fiiaing these substances in air. My brother !if:r>efated out this morning that there are amral pieces of apparatus for doing this. II has seemed desirable to a number of the ^en who are here that during the next cou '. pta of years, while we are in a position of learning, that we endeavor, if we can, to ... teefine our analyses to one piece of appa- , so that at least our results will be as aparable as we can make them from place r\~.^ place. y} ; l don't know much about this phase of subject: perhaps, Mr. Cook, you have t idea or two about that. b:': - Barren A. Cook (Chief Industrial Hygienist, Bureau of Occupational Dis- i-`} **'ai State of Connecticut Department of `. *alth, Hartford, Conn.). On the deter- *k>ation of the halowax f wonder if it T^dn't be preferable to have Mr. HemTiVdiscuss the method he has been using >'+*^"Ibout the country for the determina- f chlorinated naphthalenes. Cecil K. Drinker: I think so far ** concerned it is best to leave that "t.j l*cussions with Mr. Hcmpcrly and Dr. afterward. Rut the question of **^*^nining some uniformity of technic for 4t least is, I think, a matter of geninterest to us. Mn. Warren A. Cook: I am not quite sure that l have in mind exactly what you want in that regard. In connection with sampling? Dr. Cecil K. Drinker: Yes, In con nection with the whole technic of determfning the material in air, length of sampling, type of apparatus, and so forth. It has been suggested thnt we 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, which many of the plant* 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 scries of results which will represent average exposures of workers to chlorinated naphthalenes. In getting that figure I think that it is of great importance that we should consider average daily exposure. There is a tendency very often in taking samples of air to determine maximum exposures, to get the exposure over a 15 or 20 minute period when the worker may he actually tending a pot where the material is being used, whereas during the subsequent half hour he may be 40 or 50 feet away from that particular location. Therefore, for one thing, it seems to me it would be extremely desirable to obtain in formation in as many plants and a* many locations as possible of the average expo sure, taking into consideration not only the worker's msximum exposure while actually ~l:T 1 i:#I ; pif 'll m <Hl % 904335 STLCOPCB4023611 306 JOl'RNWr. OF IXDl/STRfAHYGIKNT: AND TOXICOt.OGY (.sepl. ;JJ7 at work with these materials but also his much smaller exposure and possibly even the projects which we shall carry out lack of exposure as he may go to other parts that time. ^ of the room or even to other departments As I have not given this consideration, l" 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 re seems to be extremely desirable to have is problem here and one that deserves concentrations of the chlorinated naph study. thalenes at certain reference points. I believe that Mr. Hemperly very carefully Dn. Cecil K. Diun-keh: Would it be of ` duplicated these reference points in each service to the American Public Health Asm- of the plants where he took his determina ciation Committee if a sub-committee froia tions. He took the samples, I believe, at this meeting, collected perhaps by my breathing level and a certain measured dls-' brother and those of you involved with th. tance from the pots where the chlorinated problems, were to make a recommendation- naphthalenes were being handled, so that to the A. P. H. A. as to the things you hart'? next year he could go back to those same brought up and aa to suitable apparatua,-. locations or others could take determina and let the final statement come from tha' tions at those same locations, which are Association after they have considered that, definitely fixed and recorded, and learn material? whether, due perhaps to clogged pipe lines or to fans which might become loaded with Mr. Warre.v A. Cook: I think that- the condensed chlorinated naphthalene, would be a splendid idea because we hxTij there might be poorer ventilation than origi a bulk of information on this particular nally designed and higher concentrations material. A number of individuals him- of the chlorinated naphthalene than origi given much thought to the development of' nally determined. apparatus, both the combustion method It seems to me that it would be an ex which we have here and also the continu tremely desirable thing to have made avail record type of apparatus which Profc able for all of us who are making these Drinker mentioned this morning. I th determinations these reference points so that it is a sufficiently important project that in Massachusetts and in Connecticut, that a sub-committee made, up from this at one plant or at another, a considerable group could give that committee a very group of workers could be taking samples at definite steer. this one particular point with reference to [Personnel of the Sub-committee: W. A-- the source of generation of the vapor. Such Cook, chairman, A. L. Coleman, H. D. 3* results would permit a comparison of knowl kins, W. II. Fulton, S. W. Gurney, 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.] committee of the American Puhlic Health Association which is charged with the devel Mb. Hervet n. Elxins (Chemist, DirK opment of chemical methods for determina sion of Occupational Hygiene, Massacho*: tion of atmospheric contamination such as setts State Department of l.abor and Indus that now under consideration. It seems to tries, Hostnn, Mass.): In connection wi^ me that it might lie a very desirable project what Dr. Schwarts has said, I am not but* for that committee to consult with the in that I am in complete agreement as regard* vestigator of the Ifnluwax Corporation and the use of skin lesions as-warning agenU. suggest to all of those who arc doing work It is my understanding that in insulated of this type, after some discussion, what wire plunts the chlorinated diphenyls sr* reference points could lie adopted and also very commonly compounded with the chlo what should he dime in councctiou itit get rinated naphthalenes. It is also my uoder* ting these average exposures. Asa matter standing that these arc more likely to cu* of fact our rommiltec will discuss that very a severe akin irritation than the straign feature and possibly inrlude it in our report chlorinatrd naphthalenes. On the 0 " . W&&SS3& 904336 *53 r M One ei^ rT out eration, jt 'onneetejfl. 'e a retl'g vca sota*3 it be ofj Rb Aaao.? fee fron3< by my-'> ith ( ndtio*|? ou btr*": Jantoi^ -om tV ed tiut ojecil W*? Ha'S-*, -v . "*71 effects of chlorinated hydrocarbons 307 (tom Dr. Drinker's work one would to attempt to get the concentrations low. !&'''' iSrt that the straight chlorinated naph- We saw this morning that the effect of these de was nearly as toxic at least as the products was on the liver and that if some B^'fchrfore of it with a small amount of chlo- one working in these products developed ItT'-skated diphenyl. liver damage from some other source the the condenser factory where we had chances of his having serious trouble was SV^itir case* there is no chlorinated diphenyl increased. Therefore, inasmuch as there is and no acne of the type described in no test to tell whether a person has had liver 15^%^ sports on the insulated wire factories. disease, certainly in the preliminary medical examination of applicants for work the his ^MD*.R.Ehmett Kelly (Monsanto Chem- tory at least should be gone into very care ly-i faiQo., St. Louis, Mo.): I can't contribute fully for a history of previous liver diseases. ^i'^ytJungto the laboratory studies but there There are other things that should be been quite a little human experiraenta- taken into consideration also. One is the fpgiiln the last several years, especially at history of syphilis, because syphilis docs ^X'^cplmts where we have been manufactur- have an effect on the liver. If there is any |vU*lhli chlorinated diphenyl. It has been history of syphilis I don't think that that observation that although on one occa- man should be hired. A ICnhn test should 4m we did have a more or less extensive be taken and I think that it would be a good |V4 (fries of skin eruptions which we were never plan to take Kahn tests on men at stated to attribute as to cause, whether it was intervals, because they might develop t?t-~S*prity in the benzene we were using or to syphilis after they are hired. chlorinated diphenyl, we have never had i think those things should be done even systemic reactions at all in our men. though we feel that if the concentration of t'-J-.V* hare examined them very closely both these vapors in the air is kept as low as was ^froca what laboratory tests we thought recommended this morning, the chances of f,\o B(ht help us and from the clinical view- having toxic effects are very .small. jg^Pftat. Also from chlorinated diphenyl there have been no cases of systemic Mr. F. R. Kaimer: I would like to clarify g reported. a point of Dr. Hookey's. * I don't believe that we can transpose the You mentioned at the beginning of your fcboratory results into the actual humans talk that your experience in acne condition without paying considerable attention to was more pronounced from the compounds 4* volatility of different substances and the of various materials with chloronaphthalonc jdry**7 they are being used. than with the straight chloronaphthalcnrs. Did you mean by that, that the acne condi J-- John A. Hooket (Consulting Der tion actually was more pronounced with the matologist, Halowax Corporation, D.ctroit, compounds than with the straight cldoro- I have had considerable experience naphthalcnc or was thatducto the fact that dermatological angle of this prob- you were in a plant operated in a different . ty*" ^he experience at the Halowax plont fashion? In other words, you handled your Jjjjf*^^Jmdotte definitely was that the dermo- numerous wire compounds in inure of a L(fli. did increase when compounds were botch operation. That is my understand rather than the straight chlorinated gjjjphthalenes. ^Flx>m the discussion we have heard today ing from Mr. Brown. Is it a fact that the straight cldornnnph- thalenca are less harmful in so far as acne hservation Dr. Drinker mnde is concerned or is it because of the handling chances are that dermatological of hatch compounds? eni* w'^ disappear along with the other y|ir;. P^hably true. However, I think that Du. John A. Hookey: That is a question Precautions, certain insurance mcas- that would be difficult to nnswer. 1 based zfaVT1 ^ou might say, ahould be taken in my statement on the fact that in taking a men who are going to work with general survey ol these cases after I started Products, even though we are going working with them the men in the plant said y04337 Vft JOIT.NAL OF INDUSTltlAL HVGIKXF AND TOXICOLOGY [S,pL lip* that they developed arnc more often and more severely after they started making compounds. It may he that it was in the method of the handling. Mn. F. H. Kaimer: You say that the con dition increases with the increased chlorine content and we are attributing the acne pri marily to the chlorine radical. If that is true, what are we to associate insofar as these various other constituents are con cerned, such as various plasticizing agents? How much do we know about those insofar as development of acne is concerned? Some of these compounds have a half dozen con stituents in them other than chlorodiphenyl and chloronaphthalcne. We are at the present time considering the chloronaphthalene as the basic element responsible for the acne condition which we have. We know very little about what the other mate rial 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. Louis Schwartz: It is well known in industry that there arc many compounds that cause acne. For instance, paraffin acnes and oil acncs have been known for a long time. Paraffin acncs, wax acncs, are simply a mechanical plugging of the fol licles of the skin by the minute particles of wax that fall on the skin. I think that the acne caused by these chlorinated naph thalenes and diphenyls, because it is caused by both--I was down at the Swan Chemical Company where they make chlorinated di phenyls and they have acne there just the same as over at Wyandotte where they make the chlorinated naphthalenes -- l 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 comcdonc becomes infected and forms a pustule. Tliry don't all pustulate because they don't all become infected. Many of these men never have any pustules. They just have little white elevations on their skin. in those people who arc in the arnc age, the youngsters of 18, 20, 22 and 23, acne vulgaris is mnst apt to occur. The sebe.7 ous glands arc most active and they scenju' have it much more than the older people whom the sebaceous glanda are not active. We keep a clipping of all articles relati 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 chlorinate," phenols and chlorinated benzenes and sol waxes, it seems that this acne-like coi tion is not peculiar to halowax or chloi ated naphthalenes or diphenyls hut ctl occur with any condition that blocks up ttii sebaceous follicles of the skin. Dr. Rotal Meeker (Special Agenf;* State of Connecticut Department of Labor^ Hartford, Conn.): I am full of question As a statistician I am a little bit suspicions^ of averages, so I should think that we should] take maxima as well as averages in getting l at the threshold dose or the dangerous inwj pregnation of the atmosphere with tbewl poisonous compounds. I just wanted U! drop that as a hint for this committee t*j consider in its work. In spite of what you said at luncheon,-*- Dr. Drinker, I still think it is rather impor*^ 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 cd! the skin or whether they are plugged, asw^ many doctors have informed me, from inside,- as it were. The fumes are breathed, tb*^ substance gets into the blood stream, thrown off through the pores of the skin sndj the pores are plugged, i think it is rathtfg important to determine that because ttj seems to me, from the slight knowledge thita I have of the industrial application of wax compounds in insulating wires, the plugging of the skin, if it is just an ( side plugging, may take place cither fro^ handling a coating on anlid substanre the wire after it boercomfroesmco&ld*-1 I haven't heard anybody say any*- about those Massachusetts cases of severe dermatitis and I am not so sure! b! ail what there was some question of liver dm*^ age there. Nolrndy has said anythingab01^,! them at all. There is no question therf' *!* > *1.1*. tht Sri'11* jfcd ro aid *> &* | thin Dr. Dri K**. bar* be t^rious jj^ptol W dip Ml ter W done firue, ^ " Corpora It U witty c ;fix&iflA " ftfi coat 'f. ' Hied b: V eadono , " or 'ber Ir,w r. e&der h SVP General Corpora *y el* l5/Yc Wdp the * V* beta me .burnt *d wire .tare thi fact thi beniezr Wt 904338 STLCOPCB4023614 \ *;)%y 5fS'.V MS* !\J* l>< *- EFFECTS OF CHLORiXATKD HYDROCARROXS 309 lie condition, whatever the complica- wax we had a head start as far as (he have been, came from handling SfrfBt a con"finedj -a-r-e--a o./f c_o_u__rs_e. j^3XXiVMi.(2Ddrninkktehr-i,i nth-eaend, syaogureaantddyeoaul mr oarsesosctuiadteys. ventilating system was concerned, since ours was already installed and adaptable to tahamnmn TMme.lt ,n'^ & bcnzcne so,vcn t rather been able to give it as yet. All I am toTeen the ? C'\mp<'und- ' rder about is the way we can administer ggiorU about :>pr'}t*ctive *al30r *a"3 in ort*cr to Prt<-`ct the employer and the employee. ** uincs of a highly volatile solvent under control wc did develop a prac tically complete enclosure for the container in which the compound was placed and sJ`t"lSSmJfti-jo*tik*eh*tietlnonesd with very grea.t..i.n..t.e..r..e..s..t..to the o.f sugge_st.e_dJ_p_oLt_s ffo_ritth_e__a_p_pIl!i- rSfytTon o.f .hailo__w___a__x_, c.lhulo.rjinka.tie,.d.! naphthalene exhausted that container in order to prevent any escape of the fumes from it. When we changed to the halowax compounds we fol diphenyl. It seemed, to me that they lowed the same scheme of applying the very much to be desired. I don't see compounds and used a completely enclosed the application of the halowax com- pot. There is a hole in one side for the wire ^Sftqad. If it is necessary, as I assume it is, to go in and one on the other side for the His rather dangerous substance, can't wire to come out. There is enough exhaust U done in a practically closed pot. If you suction on the enclosure to prevent any 'l|;pi4ae, Dr. Drinker, I wish you would ask fumes from getting out of the openings " ,?Xr. Reeves of the Rockbestos Products where the wire enters and leaves. Of course iV Corporation to tell how they have handled periodically it is necessary to open the pot " ' |L If I am any judge of equipment and to replenish the compound or make adjust 'y-miriT devices they have come as near to ments. In that case wc have the ventilat H- tA/litadniting entirely from the atmosphere ing system interlocked with the door that contamination from fumigated or evapo the operator opens so that when he opens rated halowax as anyone. All of the appli- it he increases the amount of air travel ^tBtloa of halowax, either in the melting pot3 about ten-fold. where it is applied to the wire, is done rW hooding and with ventilating appa- Dr. Royal Meeker: What is the veloc .f.gitoi, and it seems to be entirely adequate. ity when the door is open? . M*. B. H. Reeves (Vice-president and j-.r.Oeoeral Manager, Rockbestos Products f*,C*rporation, New Haven, Conn.): I will be glad to tell of our experience if it will the picture along. Our experience lias i',V*moreorless parallel with Mr. Kaimer's /-ha*much as we manufacture the same type M *!re. We have avoided the serious pic- that he ran into, probably due to the ( fhat shortly after 1923 we were using ^Wne as a solvent for asphaltic materials. , * St into anemia difficulties with benfumes and had to install a complete tllating system to remove all those from the machines that applied the Pounds to the wire. Following the lation of that equipment we were able * substitute for benzene, so we got it the picture. arc still in the same fix as every one . u far ns finding a substitute fur halo"There is none that we know of. Con- v^S.uently when we went to tlie use of haio- Mr. B. II. Reeves: With the door wide open, at breathing level the velocity is 2UO 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, because there will be condensation inside the pipe to cut down the air (low and reduce the vcntilatiun efficiency. Dn. Royal Meeker: What do you think of that trap device shown? Mr. B. H. Reeves: [ don't know what to think of that. I don't know whether it would he practical or not. I was going tu nsk Dr. Drinker whether in passing the air laden with tmlmvux fumes through tlie boxes of rats there was any deposit of halowax in the enclosure. m wJ .-'S'&L - .-ip m riX'W' Sfe. .1 v .v,e>. v.. p."" ;y. k- 904339 STLCOPCB4023615 rajs'.-l . fp:;i ; 3*1; ` . * I-Tll I , V K- . :r !}>:; itf . ' ii . ; ; . kiiy'1 1 m IfilFb $ 310 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY !-S.- Pt. lit,} I)k. Cecil K. Drinker: Yes. It is detectable readily through the outflow pipe. Mr. U. H. Reeves: Those in the far end probably didn't get the concentration. Dr. Cecil, K. Drinker: We change the position of the boxes each day. The ones furthest away move into the nearest posi tion, so that over n period of weeks all are exposed equully. complaints wen* bona fide. Wr had nodSfv' Drurty in handling cold wire and the had no skin trouble. Yet when they <jy' the same thing with possibly the applicn^ of heat in tunnels, ships and so forth tl .actually did develop trouble. We have used, of course, the icterus inde^1 in following some carbon tetrachloride eue and I wondered what you have to say sbo^' that. Is that of no value at all in the of liver damage in this material? Dr. L'mf.ry R. Hayiiurst (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. D. 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 we have found a slight advantage in doing so it hasn't at ail 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 cnils after you lmd collected it and it would involve rather complicated procedure. Dr. B. L. Vosborgii (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 ami cables in tunnels, in enclosed spaces, splic ing them together and doing all sorts of things. I am not at 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 we were having a hysteria of halowax mania throughout the country. Some of their Dn. Cecil K. Drinker: 1 don't think i until it gets so extreme that we know ituyj way. ' Dr. B. L. Vosm-RGit: I did write dowa few questions that came to mind. Somei them have been answered and some foolish but 1 shall ask them anyhow. It occurred to me that if trichlornapW* thalene has been proved to he practically innocuous, isn't it a problem of restart^' largely for the Halowax Corporation to only that one material adopted with oi known chlorinated compounds to meet tit requirements of customers? That is oo of the foolish ones probably, but I shal just ask it. <*' Furthermore, how long is it reasonable expect the liver to recover after it has beta pretty well damaged. I talked to you sad you said you hadn't worked that out trili the animals as yet. Dr. Cecil K. Drinker: In that case i set aside a certain number of animal* recover, after knowing that a certifa^ amount of damage bad been done. The^S we started to kill them but we invnrilbfyf rnn out of rats before they ran out of lesioofc.^ We don't know how long it lasts. I)n. H. L. Vosnciioit: Have you them calcium nod glucose ns you would wi i carbon tetrarhloride? Dr. Cecil K. Drinker: Not yet, butt ^ arc doing an experiment now with one on a very high calcium diet and n0 *" j group on a calcium free diet. The t* 0 j question of calcium in the diet, of milk daily to these people may be wo while. w:: f&j&F Th *3" fts* '>d340 STLCOPCB4023616 ir^Jlrc/L 2&ZS jT^j />J.'" if^'u ^ 7] EFFECTS OF CHLORINATED HYDROCARBON'S 311 m' fi*'-* D*. B. L. VosBCtinit: I just had those mm rSo^-S>J'a'<i ^-lt-nn- Bi:n-ronm'ninwd.oulId would say 113 like to hear to tho pos!,`' F*? using only this one innocuous 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 j|\?| jyarinsU*! naphthnlcne. . consideration to seeing that conditions are proper and suitable for them to continue Sandford Brown: That would gtS-pitfT our problem exceedingly, not only S^^iths commercial standpoint but from % loxiclty standpoint. But if we did so 3^ tUak that Mr. Kaimer would be the first because he wouldn't be able to get tsehnical effects he desires in the cable. working for you and that they have proper treatment. In other words, I don't believe that is a good or sufficient reason for dis charging those employees who do develop syphilis. We have not found that to be true in other places and I question whether this is one of the places. I may be in error. "ftfSUS' thing applies throughout all the where we are using these higher -?':*itoriasted products. problem as we see it, and it is one 4kh we intend to study further (we have "mm program for this continuous work that &H1 be done under the diiection of the '-DHafctr brothers), is to try to find a line of ^dmireation and whether or not within this (japilcited chemical structure there is one thing that causes the trouble. If Vt eould take hexachlomaphthalene and 'wots 1 per cent of some unknown constitjXrtttt with which we are not now familiar isd eliminate the toxicitv, that would be ^ferdy solution. Whether we will ever be t&fa to attain that I don't know. That is Wof the things we have in mind. I said before, that is one of the things which all manufacturers of these synj organic products are confronted at l**8 rtage, either in their laboratories or in ;jj.?*Iaerc'sl developments. It is largely a :Jwhon of timing as to when you should do rrk, how much you should do, and you know how to do it. You have fcwm that first. Mr. Sandford Brown: I want to take this occasion to express on behalf of the Halowax Corporation my thanks for the excellent cooperation we have 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 thi3 on an ethical, scientific and constructive basis. In collaboration with the Monsanto Chemical Company we have a much more comprehensive program in view to carry on. Therefore we 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. Hempcrly has run into some very interest ing situations in the various examinations he has made. I know that he would tie glad to relate them and give the benefit of his experience to the heads of any of these state Cecil K. Drinker: Unless there is U,e other important matter I will declare adjourned. departments who will have the direction of this work. Otherwise I can sec where we will be unable to get the full cooperation of not only the individual workmen but the plant foremen and the management, and we .. . Saters: May I say a word must have that if we arc to get the results **h` . rc8ar<^ t " hat Dr. Hookey stated that we arc shooting for over the next sev _^ ^ you arc going to eliminate eral months or yenrs. This thing may con jjjW ,your workers who hap|>cn to develop tinue, probably will continue for years. .! it 'll iai M i'MV. -m .`i STLCOPCB4023617