Document Vj46p4n2162Xavgn9kwODe3Dq

*;/- v's7/<u / > ..... . 4*V .. si- , i- v ' /'?, j1,." " U V"" >: ,,.' jf ...... ` l' s:>,'''-'`\ .;:'t;?P>y - - "'Jllli ' ; '> . ,, s'.p1 'I-- <v.\ ''. . ' '<*"" .', ~TMln- .f -*`.j r;'-iii>'j;f^,i,,r. 1 : " =:-v ' <[>%? -*t ,, .$r _ *<-$ LOGY M. */, no. 1 '.h some of the terms, old have been well to ; in genera] between decta, as with many '.tie similarity and the iy the more serious. Semen's compensation -. on industrial health, occupational disease ve been mentioned, i of occupational dis>-e and specific) with .- disadvantages are two. rst-Aid Treatment of / the traumatic in-. een care of in another 'rst-aid a few words ul describing what to . poisoning, cyanide, -;ere the patient is still ompt fiction is neces- one compact volume 'le much information d health that otherreference to many .nning students of in industrial safety and relations, it should ik. The operating will want more comthe particular expo und the industrial ! in prevention, will ineering methods of j. By E. IT. Baader, E ATP DEM OEBIETE . ttek". Adam and :PP. 104-128). eluding the history Leas well known :er are included: the - seen in England in s earners of genera.nd the liver cancer :he Kaff, caused by .'incus.--L. Teleky. THE JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY Volume 21 FEBRUARY, 1939 Number 2 THE SYSTEMIC EFFECTS RESULTING FROM EXPOSURE TO CERTAIN CHLORINATED HYDROCARBONS* Leonard Gheenbubg, Mat R. Maters and Adelaide Ross Smith Division of Industrial Hygiene, New York Slate Department of Labor, New York City HLORINATED naphthalenes product is present. On the whole, C and diphenyls, because of their the higher the chlorination, the more electrical, heat and moisture- toxic this material becomes. In the resisting properties, and because thmeaynufacture of chlorinated diphenyls, are non-inflammable, are used exten - CtH is converted into CuHio which, in sively for insulating wire and in the turn, is chlorinated to CuCIjo; the manufacture of electrical condensers. The chlorinated naphthalenes are naphthalenes in which one or more of the hydrogen atoms has been replaced by chlorine. There is, thus, a series of these substances beginning with monochlomaphthalene and going on to the octochlor derivative. In in dustry' they usually occur in mixtures in which more than one chlorinated substitution products range from the monochlor to the decachlor diphenyl. A rather characteristic acneform skin eruption resulting from exposure to these substances has been recog nized for a great many years--indeed, ever since they began to be manu factured about 25 years, ago. These skin eruptions came into some prom inence in Germany' during the war and have been attracting sporadic interest * Received for publication September 13, 1938. _ i The chlorinated naphthalenes are some times referred to as "Halowax" by pur chasers and users. While the Halowax Cor poration manufactures these substances, it also manufactures many others. Since the term "Halowax" is merely a trade name for substances manufactured by this Company, it should not be used indis criminately. In all instances, substances soouid be designated by their chemical nt-mes only. in this country ever since. An in vestigation of this condition, as it ap peared among a group of young work ers engaged in the manufacture of electrical condensers, was reported in a recent issue of this Journal (1). Experience has shown that the medionl practitioner.io otiH-somewhat--unfamiliar with the skin eruptions, even 29 m m 00038 WATER PCB-SD0000032501 'l m Jo] mi f 30 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY M. tl, no. t though they are by no means uncom- and (C) given off at 192C and 172C -Tgorr-m-tfae -industi ins tvfaei e ihirrrhiir" -reypeerirtfy:--targe doses; approx-- rinated naphthalenes and diphenyls imately 15 mg. per kg, were injected are used. The reason for this is that subcutaneously each day. any one physician is likely to see such Animals receiving compound (A) cases only rarely, unless he happens and the sublimate of compound (B) to be practicing in the immediate vi showed no lesions attributable to these cinity of one of these factories where substances when killed at the end of large numbers of workers are em 2 months. The 30 animals, however, ployed. That the relatively rare sys which had received the higher chlo temic effects resulting from such rinated compounds (B) and (C) and exposure almost invariably go un the sublimate of (C), all died in from recognized is not surprising under the 12 to 26 days. Autopsies uniformly circumstances. It is of the greatest showed extensive damage. importance however, that physicians The next important study to be become acquainted as promptly as pos published was that of Drinker, Warren sible with the clinical and pathological and Bennett (4). These investiga pictures presented by these patients, tors administered chlorinated hydro particularly as regards systemic ef carbons by inhalation, subcutaneously fects, since failure to detect early and by mouth, to white rats. Mix clinical manifestations of toxicity, and tures of (a) tri- and tetrachlomaphtha- to remove ' susceptible individuals lene; (b) penta- and hexachlomaph- promptly from further exposure, may, thalene alone, and (c) with 10% refined on occasion, result fatally. chlorinated diphenyl; and (d) chlori Review of Literature ok Systemic Effects* nated diphenyl were used. Briefly, these experiments showed, that the tri- and tetrachlomaphtha- Experimental studies.--The first lenes produced relatively unimportant mention in the literature of systemic pathological changes in the liver until effects from chlorinated naphthalenes extremely high concentrations were is that of Lehmann in 1919 (2). He used. Animals exposed for 6 weeks to found that animals which were fed or the higher chlorinations, however, in which inhaled these substances lost relatively low concentrations, regularly appetite and at death showed "pecu showed minor degrees of liver damage liar" lesions in the liver. even though, as a group, they gave no In 1936, Flinn and Jarvik (3) ex clinical evidences of such toxicity perimented on rabbits with three dif while alive. Exposed to still higher ferent compounds; (A) a mixture of concentrations, the rats lost weight tri- and tetrachlomaphtbalene, (B) a mixture of tetra- and penta-chlornaphthalene and (C) a mixture of penta- and hexa-chlomaphthalene. They also used sublimates of (B) and appetite, and began dying after 8 days' exposure--many with severe jaundice. Examination of the liver of these animals at autopsy revealed marked central fatty degeneration * A review of the literature on skin mani- with necrosis of liver cells. festations'hppeared in the article by Mayers and Silverberg mentioned above (l). It is of considerable interest that - tbe exposec . cal evidence XS^MIrom acute wteu given Mgtetrachlorid control anin . oth< 'tgS^i'^lirought out which marked paliver) no ab the1'other o common in .M3# but rather 'from acute y I;(2)' even th ;logical chanj ViOT these ch -' VIkSP'lower co 'very Jxal'months after cases of syst chlorinated : 'Utp^rare m spite flr^l'-these substa doubt th ports has bee: fact that cas ; Y Ire . unusual ibent of i. -- appearing to "Important r61e . ;>.!' tion--and se< 'd;;--- part of physic poisoning. I been general i theological j rinated hydr< . still relatively able regarding "f-x industrial pois The danger "yU- of knowledge : tion that rece ,*3003!) WATER PCB-SD0000032502 to be arren stigahydro:ously MLxphthamaphefined chlori- .owed, jhthaortant t until were ;-eks to .rer, in ,-ularly, amage ave no oxicity higher weight after 8 severe e liver vealed .'ration ; that Fib. 1939! SYSTEMIC EFFECTS OF CHLORINATED HYDROCARBONS 31 ^ the exposed rats, which gave no clini- tion of the Labor Department in New l'. cal evidences of disease, promptly died York State, in which a physician had from acute yellow atrophy of the liver been treating a severe case of jaundice when given a very small dose of carbon in a young woman exposed to chlorin ^tetrachloride--a dose well tolerated by ated naphthalenes. After a long and Vcontrol animals. _ serious illness, when the girl was on ,J|jJriTwo other points of interest were her way to recovery, the physician |f;p^brought out by the study: (1) in the expressed the opinion that within a kv.rats, which on autopsy showed even few weeks she would be able to return vjf! marked pathological lesions of the to her former work. Whatever the no abnormalities were found in cause of the jaundice in this case, there r the other organs--a finding not un- is good reason to believe, on the basis common in experiments on animals, of the experimental work previously but rather rare in humans who die cited, that further exposure to such, ,-;*$*|from acute yellow atrophy of the liver; substances would have entailed a ?" ;us|||jf(2) even the less important- patho- grave risk to the patient's life. ~ changes induced in the liver by In 1934, Courtois-Suffit (5) reported ; chlorinated hydrocrbons in the on the work of Touraine who, with ; :jbA`[_}ower concentrations were found to be his associates, examined 60 workers ex A-hr^yery persistent, being present even 2 posed to trichlornaphthalene and r.-'i^rKniROBths after cessation of exposure. found mild digestive disturbances and Clinical Reports.--Clinical reports of dizziness in 13, but nothing of a more H^g^.casea of systemic poisoning from the serious nature. ' ''t^^^Wormated naphthalenes are as yet In 1935, Schwartz suggested the , . V.^^.rare in spite of the length of time that possibility of systemic disease from '''f^fethese substances have been in use. exposure to these substances in a talk .%/!$? doubt the infrequency of such re before the American Public Health . ports has been, in part, due first, to the Association (6). ^vv.fact that cases of systemic poisoning In 1936, three fatal cases of jaun ' & are unusual occurrences--the ele- dice in chlorinated naphthalene work ----- ~t5rI?eilt f individual susceptibility ers were recognized in this country. :\1 appearing to play an even more im These were reported by Flinn (3) and . portant r<Me than usual in this situa- Drinker (4) who summarized the cases . ,, :j-l ^on--smd second, to failure on the briefly. Part of physicians to recognize cases of All three of the men were young and _ poisoning. Until recently there has in none could any predisposing cause -A been general lack of knowledge of the .'..'toxicological properties of these chlo rinated hydrocarbons, and there is still relatively little information availa^e regarding the clinical picture of Industrial poisoning from them. other than their industrial exposure be found to account for their illness. Two of the men who had worked side by side died within 2 months of each other. Both had been exposed to mixtures of penta- and hexachlornaphthalene, and one had been < The danger that lies in such a lack exposed to a mixture of tetra- and of knowledge is exemplified in a situa penta-chlornaphthalene with 10% tion that recently came to the atten chlorinated diphenyl. In both, the I--- ft mm -- a| if v. .-fifel [r'-'S -A "> MY,| Mil T* * vF A 1V .a OQO'IO t WATER PCB-SD0000032503 Jo! ji > 32 JOURNAL OF INDUSTRIAL Hi'GlK'A'L AND TOXIGOLOGY--[uni tt, ng. diagnosis of acute yellow atrophy of the liver was made on autopsy. In the third case no autopsy was reported, but death occurred after an acute ill ness characterized by jaundice. In one case dermatitis characteristic of the effect of chlorinated naphthalenes had preceded the jaundice. In addition to these fatal cases, Drinker (4) also mentions four cases of non-fatal jaundice among indi viduals with similar exposure. No details are given. Case Histories Because of the obvious need for more clinical data in regard to the effects of chlorinated naphthalene ex posure, we are reporting 3 cases in persons who, after exposure in the course of their work to these known hepatoxic substances, died of acute yellow atrophy of the liver, and in whose cases no other etiological factors could be discovered even after very careful investigation. The first case was seen in consultation at the Lin coln Hospital in New York City by Adelaide Ross Smith. The second and third cases were seen in consulta tion at the New Haven Hospital by Dr. Leonard Greenburg, (now Execu tive Director of the Division of In dustrial Hygiene of the New York State Department of Labor) when he was Commissioner of Health of New Haven, Conn. The plant conditions under which the patients had worked were carefully investigated. Cast l. H.F.* A 17 year old girl was admitted to the Lincoln Hospital, New York City, on the Grateful acknowledgement is made of the courtesy extended by the staff of Lin coln Hospital and the Medical Examiner's Office in granting permission to use the records in this case. service of Drs. Kenneth Taylor, Edwin Hauser and Scott Johnson on April 26, 1932 in a semi-comatose condition. She was intensely jaundiced on admission. Her past medical history, obtained from members of the family, was entirely nega tive with the exception of a tonsillectomy in 1930. Until the onset of the present illness she had been unusually healthy and free from symptoms of any kind. The occupational history was as follows: After being gT&duated from grammar school she attended high school for 1 year and then obtained a job, her only one, with a concern manufacturing electrical condensers for use in radios. She worked at this one place for 7 months and stopped working there 7 days before her admission to the hospital. Her work consisted of soldering and labelling condensers. It is possible, from the information given, that she may also have assisted in the sealing operations, but this could not be definitely ascertained. In any event, in the soldering of the con densers Bhe was exposed to the fumes of triand tetrachlornaphthalene with which the condensers were originally impregnated. At the same time she was exposed to fumes of the higher chlorinated naphthalenes from the sealing operations conducted in close proximity, to the tables at which the solder ing was done. The present illness began about 5 months before admission to the hospital--or ap proximately 2 months after starting work in the plant--at which time she noticed several pigmented areas on her face. These con tinued to increase in severity and extent, and caused her to visit the outpatient de partment of the Lincoln Hospital. Herej sugar was found in her urine and she was referred to the skin clinic where a diagnosis of acute catarrhal jaundice was made. Her rectal temperature, at that time, was 100. A diffuse papulo-puatular eruption was also present on her face. On being questioned about it, the patient stated that it had been present to her knowledge for about 2 months.t From then on she suffered from f Investigation revealed the fact that some of her co-workers were also suffering from a similar acneform eruption, and one girl discontinued her work because of it. None of these other girls suffered any systemic disease. irV-- -MvRttg! 8YST Teasing weaknes ^petits:was poor; h ^lively more jaundi -ifdh Increased. . jbibont 6 weeks ffi'other noticed th. fjfbout 3 weeks latf i severe headach tied. This was ijfpuffLneBs and swi ffal and abdomen jgftiSha continued i jkweek before adn ''admission she 1 Jiadvementa of the 'iary, bobbing of Arith ' any pain, ^seemed to develo ^dhange in mental the hospital in th ^This was the firs ij^curred. She arri state of prostrati Summary of p. i'cf^^fe'patient gave th $j|eolored girl alth white; ' She look -- r* developed .fo.r he. .. '^kik^quently c&sturbi contractions of t -S&S-Pciated w'th `a' . --a-s*head;' The tern a73*&,;'.D4, respiration The first ad: .'`i/jAt'Mient is so jaui More careful ex neck revealed a A-jj'llTtion beginning : f^'.qying down to, Besides this g ''(&l-i,.were three area .A-v; rest, appearing ..4^. coal--one on ea one on the cb these black spo of aggregation: rn.,\ '1 did not share ir tion. It was c \'\ teristic of jauc -T The skin oft Lj; - of the body wa ish subtinge. TsSV 000 4li^ mi WATER_PCB-SD0000032504 1, no. t Edwin 26, 1932 he was ed from y negatomy in it illness vnd free follows: AT school ^ad then concern ifor use place for re 7 days &1. ng and ,le, from nay also ons, but rtained. tne con es of tri hick the ;gnated. to fumes mes from in close a solder- 5 months --or ap ; work in d several :ese con1 extent, .ient de.. Here; she was diagnosis ie. Her ?H 100. . was also :es'.ioned had been about 2 red from 'act that suffering and one _=e of it. .-red any l&i f IMS] SYSTEMIC EFFECTS OF CHLORINATED HYDROCARBONS 33 Wy,;'] 'increasing weakness and nausea. Her ap- 'patite was poor; her skin became progres sively more jaundiced, and the pigmenta- on increased. lAbout 0 weeks before admission her frjfiother noticed that her eyes were yellow. - .. `'About 3 weeks later she began to complain " '-4W o^'severe headaches which continued un bated. This was followed in a few days by -S puffiness and swelling of the face, hands, leet`and abdomen. 'She continued at her regular work until ' '*'*v^S week before admission. On the morning '^admission she began to have convulsive pndvementa of the abdomen with involun- 'iftjr bobbing of her head, unassociated 'With any pain. At the same time there, ^seemed to develop memory defects and a change'in' mental status. On the way to M thahospital in the ambulance she vomited. p,ThIs was the first time vomiting had co ncurred. She arrived in the hospital in a ';fstate of prostration. of physical examination.--The i gave the impression of being a r" -^Sficolored girl although she was, in reality, :`i:.>'^^^gwhiteA'. She looked well nourished and well *. ''.i^S^cteveloped for her age. There was general - puffiness of the face, hands, feet and abdo- - - -}i-^^THenr' She was hiccoughing, and was fre- ` f^^'queally disturbed by a series of tetanic .'.jusSSe contractions of the abdominal muscles as30- with involuntary bobbing of the . '_i^i.head. :..The temperature was 100, pulse ' respiration 26. _-' The first admission note stated, "pa- ,'C;.tient is so jaundiced her face is black." ..,.;SMore careful examination of the face and J'iVn'eck revealed a negroid type of pigmenta tion beginning at the hair line and extend ing' down to, .and including, the neck. .yV> Besides this general pigmentation there were three areas somewhat darker than the vr:_.rest, appearing very much like dab3 of char- ne oa eacb cheek below the eyes and :,r one on the chin. On close examination aU.these black spots appeared to be the result aggregations of comedones. The scalp i.v:' ^ nt 8hare in the general dark pigmenta- It was of a yellowish color charac- ir teriatic of jaundice. ' ' The skin of the thorax and the lower part , the body was dark brown with a yellow- ,**h aubtinge. Over the skin of the obdo- men there was a girdle-like area of deeper pigmentation beginning at the level of the umbilicus and extending to the pelvis. There was also a line of deeper pigmentation in the garter region on the posterior surface of the left thigh about 1 inch above the popliteal fold. . Examination of the eyes revealed deep jaundice of the scleras and the conjunc tivas. The pupils were equal and regular, and reacted to light and accommodation. There was no nystagmus or strabismus. The blephoral conjunctivae were redder than normal. The discs were somewhat pale, though well defined. There was no exophthalmus. The normal ratio in width of artery to vein was preserved. The ves sels were not contracted, and did not pre sent the hair-line appearance believed to be associated with arsenic or quinine poi soning. Other positive physical findings were: slight injection of the throat; slight edema of the feet and hands; an apical systolio murmur; abdomen distended and tympani tic; liver on pcmussion small, with tympany extending to the very costal edge. Laboratory findings: These were as follows: Blood count on admission--White cells, 9,100; Red cells, 4,200,000; Polys., 80%; Lymphs, 20% Hemoglobin, 87%; Bleeding time, 4.5 minutes; Clotting time, 2.5 minutes; Platelets, 220,000. Blood chemistry: Non-protein nitrogen, 35, later 45, mg./lOO cc.;Protein, 6.9 mg./lOO cc.; Urea N. 20.83 mg./lOO cc., Creatinin, 2 mg./lOO cc.; Glucose, 88 mg./lOO cc.; Cho lesterol, 145 mg./lOO cc.; Calcium, 8 mg./lOO cc.; CO combining power,* 52; Albumin, 2.5 mg./lOO cc.; Icteric index, 230; Van den Berg, immediate direct reaction; Wasser- man, negative. Urine--Sp. gr. 1.008: Alkaline. Albu min negative. Sugar, a trace. Acetone, 1-f. Bile pigment present. Urobilinogen a trace. Few red and white cells. Stools--Urobilin present. Spinal fluid--Pressure normal. Cells: 10, Lymphocytes. Clear. Glucose pres ent. Globulin absent. X-ray examination--No evidences of lesions of the heart and Iung3; bones of skull, ribs, shoulder joints, clavicles, tibia and fibula. The gastric contents, and later, `St'.y'rT^ ' Hi a.- :*X' fe.i;- .r, - j ferity-'f:#' ISmmMMSSM A-TV'-v- ri. WATER PCB-SD0000032505 34 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [sol. if, no. T TSbr-mej----- S at autopsy, the organa were analyzed for arsenic, phosphate, lead, tin and antimony. A trace of phosphate was reported, prob ably from inorganic phosphates ingested before admission. Diagnosis--The patient presented a pic ture which was distinctly puzzling to all physicians who saw her and no conclusive diagnosis was reached at the time. The various diagnoses suggested included: ob struction of the common bile duct, toxic jaundice possibly due to some dye, obstruc tion of the inferior Vena Cava, blood dyscrasia, Addison's diabetes, hemochro matosis, industrial poisoning of unknown origin possibly due to arsenic, causing acuteglomerular nephritis and acute hepatitis; and finally acute yellow atrophy of the liver and pancreas'possibly due to an unknown industrial poison. Course--The clinical course was steadily down-hill. At 11 p.m. on April 27th the patient became unconscious and went into a coma. There was Cheyne-Stokes breath ing. . A peculiar odor was present which was variously identified by hospital physicians as ethylene or garlic. The pupils were im mobile to light. Deep reflexes were greatly depressed. There was no Babinski. Ab dominal reflexes disappeared. The skin became dusky throughout. The liver dull ness seemed to diminish. On April 28th the temperature rose to 106; the pulse to 140, and the patient died. Anatomical diagnosis--An autopsy was performed at the Medical Examiner's office on April 29, by Dr. Cbas. H. Hocbman, Assistant Medical Examiner. The report in full was as follows: Body is that of a white adult female, well developed and nourished. Cyanosis of lips, ears and fingernails. Marked pigmentation about eyes, lower lips, neck and abdomen. General icteric tinge to entire body. No evidence of violence. Some edema about ankles. Hair is black. Eyebrows black. Brown iris. Conjunctivae and 3clerae ic teric. Rigor mortis present. Postmortem lividity of dependent parts. Scalp incised and reflected, calvarium removed. Brain found congested. Meninges bile tinged. On section, no evidence of intracranial in jury or hemorrhage. Dura stripped and reveals no evidence of fracture. Body'opened in usual midline incision. Sternum removed. Some remnants of thy mus atilt present. Lungs are free. Bron chi contain a bloody mucous. Mucosa injected, has yellowish tinge. Hemor rhagic infarct about size of hen's egg in left lower lobe. This is airless and dark red in color, firm. There are also similar smaller areas in other lobes. Heart is small and shows some sub-epicardial hemor rhages. Some hypertrophy of left ventri cle. Valves thinned. Arteries natural. All are bile Btained. No significant findings in myocardium or coronary arteries.. - Esophagus is natural. Stomach is dis tended, contains some dark material. The rugae are somewhat hypertrophied. The duodenum contains green chyme. The ampulla is patent. The jejunum, ileum and large gut are natural. Many petechial hemorrhagic areas noted in the mesentery with some enlargement of mesenteric lymph nodes. Liver is small, weight 720 gm. Capsule wrinkled. ' Right lobe on section shows'*' areas of yellow surrounded by red areas. Left lobe much firmer although liver cuts firmly throughout. All ducts patent. Gal' bladder small. Wall thickened throughout. Pancreas is natural in size, somewhat congested. Spleen is natural in size. On section, firm, dark red in color. Follicles are somewhat indistinct. Kidneys show swollen cortex. Evidence of parenchyma tous degeneration of epithelial cells. Capsule strips easily. No granulation. Degenerative changes in cells of glomeruli only. No glomerulitis. Uterus is small. Endometrium bile-stained. Ovaries are natural in size; right contains corpus luteum cyst. Bladder wall is somewhat thickened. Mucosa is injected. Microscopic examination--Liver--From size of a through and through transverse section one suspects that the entire liver was about J normal size. Liver segment is very firm and composed of two distinct and peculiar types of tissue: (a) That con stituting major portion of parenchyma is red in color; firm and elastic in consistency; (b) Other areas are light yellow in color and are scattered indiscriminately throughout reddish areas. Yellow areas vary from i to 2 in. in diameter. External surface judgi iosobth.;\ 'v. . typist P , klrophy is rtf^&rea is c bjophy'' ,in w cljiaappeared, t normal to have' B(,v WoocTcells, ee ggfjnd older seal . Numerous bile J'jeem lo have fc *:. -&:;&$ generating isI j-hBpwolftfia liver c< gtror ducts. .The 1 ".javtP'Th.08 liver c y^-firegenerated a seen, in the g - . ''-mhjSXns been one oi ' ing from the d *>var .T^i^^^Skinr--Sho' $orium'' whic -tt'-j^Some. of the - .'JjjiSK^deeper. in cor ''S^^Ee&rt-Sh ., 'tS^rimyocafdial c ". dneys-- ^/--N^eratioh invol "vYi glomeruli. ] iKv glomeruli. Adrenals' zei* -degeneration -Ig^Pancreas- '."'kV;of cells of ac ji^j.v./Summary r'7ji. dently cause solving mos ,.:3; liver.. The ---- i-iJT. pnd. recovert ' M miliar natu Ji-- ufa'i a A. young .^'icitted to tb '-f-p, % 1934, com lory given r He had v Author 1-. 00043 . T-VW-' *`. *:: W!'s' '>--. r- / . MSS?:? ` ...... WATER_PCB-SD0000032506 ,g apsule shows :&3. r cuts Gail zhout. :what . Ou .Hides : show hymacells. lation. .meruli small. :a are cus !uaewhat /rib. 1939] SYSTEMIC EFFECTS OF CHLORINATED HYDROCARBONS 35 liver, judging Irom mis poriidn, was --wtrtrTrtTtrw^~from~7Trl7n3rrhe~^ddle uf- j smooth. December, 1933. At that time he felt run A typical picture of clear aubacute yel down and became jaundiced. He was seen low atrophy is revealed. Slides show that in the dispensary in January and found to jp rod., area is composed of so-called "red have an enlarged palpable liver. He then ^atrophy" in which all the liver cells have Bpent several weeks in another hospital with ^'disappeared, their place being occupied by slight improvement in the jaundice. `|heir normal supporting stroma, which In March, 1934, he returned to the job :N ^`feems to have been spared, great numbers of in the wire factory. Following this, the xjvjf'blood cells, early fibroblastic proliferation jaundice became quite intense with increase older scar tissue. In these red areas, in general malaise, anorexia, attacks of .^fenWrous bile ducts are seen. These also dirtiness and loss of weight. Three days * '10, teem to have been spared destruction. The before admission vomiting had occurred. ^yellow areas are composed of actively re- He had taken no drugs and there had been '.s generating islands of liver cells. no exposure to carbon tetrachloride or The toxin evidently has destroyed most chloroform. 'of the liver cells, leaving intact their sup Summary of physical examination--The porting . stroma, blood vessels and bile temperature was 99, pulse 74, respiration dhcta.' The latter seem to bo regenerated, 20, blood pressure 130/74. The patient was hose liver cells spared destruction have a thin well-developed man who appeared '...v^^^regenerated and havelormed yellow islands moderately ill. There was bright yellow tbe gTOss picture. There evidently jaundice of the entire body. The pupils has been one or more attacks of hepatitis judg- were widely dilated, the nasal septum de from the different ages of the pathological viated, causing obstruction on the right, v.'.y.u:---- various parts of liver.* the mucous membranes injected and the Ski "--Shows increased density of tongue moderately coated. The tonsils ' 4jA'^SEebrium which stains deeply with eosin. were enlarged and cryptic. Lungs were Vfif^^fe'SoSne' of the epidermal cells are slightly clear, heart normal, radial vessels soft, ;'y^jwdeeper m conum than normal. abdomen tympanitic, soft non-tender. The .. Heart--Shows, mild parenchymatous liver edge was felt at the costal margin. '-.V.^r^Tinyocardial degeneration. The organ was soft and non-tender. The ::;^^^'v'Kidney8--Show severe epithelial degen upper edge of the liver dullness was in the .. ^^MS^eration involving epithelium of tubules and 6th interspace. glomeruli. No inflammatory reaction of Laboratory findings--These were as fol __ jif&yiglomeruli. lows: ' 'i':S'D.T. Adrenals--Show severe parenchymatous Urine--was dark yellow and was nega _ *y.y degeneration of cells. tive except for the presence of bile and uro ' Y]v?- Pancreas--Shows intense degeneration bilin. of acini and of islets. Blood count--red cells, 4,380,000; hemo Summary--An unknown toxin has evi- globin, 85%; white cells, 6,800; Polys., '.g.'-: dently caused a severe diffuse cytolysis in- 65%; Lymphs, 29%; Large Monos., 4%; .'..yolving most of organs, predominately the Eos., 2%. Subsequent examinations liver. The latter has evidently undergone showed a slight rise in white cells to 10,000. and recovered from previous attacks of a Stool--showed bile, considerable undi ' *. '. _ similar nature.' gested food, small amount of fat. ' Case t--F. D. Kahn lest--negative. Liver function tests--Icteric index--30 to ..VL;1.';,.'A young man, 24 years of age, was ad- 50. Bromsulfonphthalein showed marked nutted to the New Haven Hospital on May . ;Y 2, 1934, complaining of jaundice. The his- k>ry given was as follows: Nr' He had worked in a wire factory coating , * Authors' italics. | The waxes employed in this process are the higher chlorinated naphthalenes. These are used in a molten state in a hath through which the wire to be coated is passed. The process is partially but not entirely enclosed. Exhaust ventilation is in use. M. 0004T w-;4\ WATER_PCB-SD0000032507 Sgjft*rr--------- -- {r.. ,v /ft;.', .MuUJU Vn im V: > < :i, I I'l.i ! f-|`! 36 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [t>of. tl, no. i impairment: 100% retention in 6 min,, 85% retention in 30 min. Blood chemistry: Non-protein nitrogen, 28 mg./lpO co.; Urea N, 11 mg./lOO cc.; Serum total proteins, 8.15 mg./lOO cc.; Serum total albumin, 2.68 mg./lOO cc.; Serum total globulin, 3.49 mg./lOO cc. A/G ratio, 0.76; Blood sugar, 68.0 mg./lOO cc.; Blood calcium, 10.32 mg/100 cc.; Blood phosphorus, 4.12 mg./lOO cc.; Serum fatty acids, 11.3 mg./lOO cc.; Serum lipoid phosphorus, 7.5 mg./lOO cc.; Serum total cholesterol, 10.5 mg./lOO cc.; Serum free cholesterol, 63.0 mg./lOO, . Sugar tolerance test was within normal limits. X-ray o/ abdomen showed hepatio flexure of colon unusually high. Course. The patient was put on a high carbohydrate diet and his general condition improved but the jaundice persisted. He was discharged on May 16, 1934 with the diagnosis of toxic hepatitis. He was admitted again on June 1, 1934 complaining of abdominal swelling of 3 days' duration, weakness, anorexia and edema of the legs which had developed soon after his discharge. The physical exam ination showed deep jaundice, systolic mur mur, abdomen distended and tympanitic with dullness in the flanks, moderate pitting edema of the legs. Examinations of the urine, blood and stool showed no important variations from the original findings with the exception of a drop in white cell count to 6,400 with 74% polys., and a decrease in serum albumin to 1.88%. Serum COi con tent was 54.54. Serum chloride was 98.0 mg./lOO ce. The patient's course after the second admission was rapidly downhill. The dis tention could not be controlled and he soon passed into complete coma. A convulsion occurred on June 8th and on June 10th he died. Anatomical diagnosis.* Extensive nec rosis, fibrosis and regeneration of liver, acute entero-colitis with edema, fibrosis of pancreas, acute pancreatitis, jaundice, as cites, edema of lower extremities, focal * Autopsies on this and the following case were performed on the pathological service of the New Haven Hospital by Dr. H. M. Zimmerman. Grateful acknowledgement is made of his courtesy in permitting use of the records. pneumonia (bilateral), subpleural hemor rhages, cloudy swelling of kidneys. Case S--C. C. A young man 22 years of age was admitted to the New Haven Hospital on February 28, 1935 with the complaints of jaundice, ab dominal pain, nausea and vomiting of bloody material. The history given was as follows: He had worked in the same wire coating plant as the previous patient (F. D.). The present illness had h.i un with jaundice 2 months previously with no other symptoms. This continued for about li months. Two weeks before admission be became more jaundiced and concomitantly de veloped upper abdominal pain, malaise, nausea and finally vomiting--the vomitus becoming bloody in character. He was treated by his family doctor with no relief. His condition became worse and he finally became delirious and incoherent. Hos pitalization was advised. Summary of physical examination--The patient was comatose, irrational and vomit ing bloody material. Positive findings of significance were as follows: Temperature not elevated. Blood pressure 102/68. Generalized jaundice, petechiae over the extensor surfaces of the arms; tenderness over the upper quadrants of the abdomen. No liver dullness percussable. Course--His condition became rapidly worse, coma setting in soon after admission. The vomiting continued. The patient died about 24 hours after admission. Anatomical diagnosis--Extensive necro sis and regeneration of liver; jaundice, acute lymphadenitis of portal nodes; as cites; perienteritis of jejunum; cloudy swelling of heart and kidneys; acute pul monary congestion; healing exanthematous rash of fore-arms. DISCUSSION These three cases show the occur rence of similar pathological changes in the liver in three young adults known to have been working with chlorinated naphthalenes and diphenyls--all were exposed directly or indirectly to the higher chlorinated hydrocarbons. In three cae failet v -- -SS.sSr*-"*<j^gbag ca U'jfirst'ca; dthy/.yoi lee absence _ ag.to li Hjng-.or. folio nces ear.';j>.` is 6f in e c: sea ap ^rf^aileast one . ... ^`f^pDprQYemeI- fe^atal'attack vSi^^^^arren and __ jii4:fi-ljn'.organs ot - tu^V.^penments "-w^^that such If jStaiL: .three of Such:; lesion: Rings' in case : *--Sferf;the liver .'^ifeowledge, r.vw.^fw^k8,-.a. y.V w- heth. e ,'_g^.gnmaxy nr secondary t w w^.fight'pf the .''iv^'I'erver, .one, w . ` -r^g>i/y?ew and s : by 1 final patholc - has l . iffi^'Drinker's ( * ^'.Sir - evidenc e expost .:^thalenes, p: .. jSSj^yellow strop . :.i^r'doses of car . to be ha This protr -/^whether dt ^atrophy of . ~.i.'v-e**x1t.&TSO-z/-.. . - 'J-t-- jifiiTSs-r WATER_PCB-SD0000032508 01 led 23, &h~ of Cllig The :e 2 ma. ,ths. ame de use, utua wza lief, sally Hoa- -The itnitgs of ature 2/68. : the rness imen. pidly isioo. : died secroadice, as'.oudy : pul.atous iccurges in nown nated were o the i. In, ftb, JM9J SYSTEMIC EFFECTS OF CHLORINATED HYDROCARBONS 37 three cases, a most careful investi gation failed to reveal any other prefdisposing cause for the condition. In first case in particular, that of a Wealthy young girl on her first job, tbe absence of any conditions predis ing to liver damage either preced ing or following her exposure to the -^substances in question is especially ^clcar. is of interest to note that two of Ltlie.cases apparently had suffered from least one previous attack of hepatijitis; followed by a certain ' degree of j|linprpvement before the onset of the hiatal attack.. . tin view of the fact that Drinker, IHdrren and Bennett found no lesions w-^yin-'organs other than the liver in their .'^^experimental animals, it is noteworthy Dvl^tthat such lesions were conspicuous in .three of the cases here reported. > ;yg|W&ch lesions, are, indeed, usual find - .`x^Sip in cases of acute yellow atrophy . T-^^^oftthe liver in humans regardless of 'th^f^etiology. On'the 'basis of present ;knowledge, it would be impossible to iSl&say. whether they_ are the result of ' -`^primary, intoxication or are merely W?j. secondary to liver damage. In the '.light of the animal experiments, how ... v^ever, one would incline to the latter -.yfiiiview and speculate as to the part 3$ played by length of exposure, in the :X final pathological picture. - It has been mentioned that in Drinker's (4) experiments, rats with `"^"no- evidence of clinical disease while being exposed to the chlorinated naph thalenes, promptly died from acute yvS-yellow atrophy of the liver when given doses of carbon tetrachloride so small a3 to be harmless to control animals. This prompts speculation as to whether death from acute yellow '.^atrophy of the liver in workers simi- larly exposed occurs only in those having some pre-existing substratum of liver damage--such as might follow an attack of catarrhal jaundice, for example--and that thi3 might ac count, in part at least, for the fact that only a very occasional worker out of a large group will suffer from sys temic effects of exposure to these sub stances. In the three cases reported however, no history was given sug gesting that any hepatic disorder prior to exposure had occurred. The presence of a papulo-pustular eruption in two cases is of interest. In one it antedated the systemic symp toms. This type of eruption is char acteristic of the dermatitis caused by chlorinated naphthalenes, and until recently was the only disturbance at tributed to them. The presence of "aggregations of comedones" such as were found in Case I is also characteristic of the skin eruptions produced by these sub stances. The question as to whether or not the skin eruption in such a case is in any way connected with the onset" of systemic effects cannot be answered, since thus far no correlation' has been established between skin lesions and systemic disease (1). It is interesting, therefore, that in Case I the skin eruption apparently antedated all evidences of systemic disease. Had the girl been promptly removed from further exposure, when it was first observed, it is possible that her life would have been saved; or had the physicians first called upon to treat the jaundice (of whatever origin) in her case, or in the second case here reported, recognized the danger of continuing exposure to the chlorinated naphthalenes, these dedths might pos sibly have been averted. \;XMktV.*'.'/-'.* . " - v. -v / eft* .1 ' 5* 5.:;. '] ifc . V.'- ffjg 1 ?' S ,, r,`- - >' llWk' "* . V ,-`l WATER_PCB-SD0000032509 fj'.Tr hi Jolli ; 3 h; ! vU in- 3 a';': ill' i.V . Recommendations tor KTedical Control 1. The authors wish to stress the need for the conscientious reporting by physicians of all illnesses occur ring among workers exposed to the chlorinated naphthalenes ' and di phenyls, particularly cases v. hich have been carefully worked up, so that the clinical disease entities resulting from such 'exposure can become further clarified and thus mere readily recog nized in the future. Fewer errors in the diagnosis and management of these cases would occur, and workers' lives could undoubtedly be saved in this way. 2. Persons suffering from the typical acneform eruptions should be removed from further exposure. . 3. Persons who have, at any time in the past, had any liver disease--even a mild catarrhal jaundice--should not work with these substances; nor should workers with a history of typhoid fever, malaria, gall-stones or other dis eases known, to affect the liver ad versely. - 4. Persons receiving arsphenamine treatment for syphilis; or those who are taking drugs believed to be in jurious to the liver in susceptible persons, should uhl be fuuhtn expused in their work to potential liver poisons. 5. Persons working with the chlo rinated naphthalenes and diphenyls, if requiring a general anesthetic for an operation, should not be given chloro form or avertin, and vice versa, indi viduals who have recently received such anesthetics should not imme diately thereafter go back to their former work or to work with other substances believed to be potentially toxic to the liver. 6. Pregnant women should not be exposed because the liver, in preg nancy, appears to be peculiarly suscep tible to injury. 7. Experience seems to indicate that by proper attention to ventilation and medical supervision of workers the chlorinated naphthalenes and diphe nyls can be used in industry with safety.' ' ^ Summart The systemic effects resulting from exposure to certain chlorinated naph thalenes are discussed, and the litera ture of the subject briefly summarized. Three liver deaths in workers handling these substances are presented in some detail, with autopsy findings. Recom mendations for prevention are given. BIBLIOGRAPHY 1. Maters, M. R., and Silverberg, M. O.: Skin conditions resulting from expo sure to certain chlorinated hydro carbons. This J., BO, 244 (193S). 2. Lehmann, K. B.: Kurzea Lehrbuch der Arbeits- und Gcwerbehygiene. S. Hirzel, Leipzig, 1919. p. 251. 3. Flinn, F. B., and Jarvik, D. E.: Action of certain chlorinated naphthalenes on the liver. Proc. Soc. Exper. Biol, and Med., SS, 118 (1936). 4. Drinker, C. K., Warren, M. F., cNd Bennett, G. A.: rhe problem of pos sible systemic effects from certain chlorinated hydrocarbons. This J., 19, 283 (1937). 5. Coortois-Suffit: fitude sur l'intoxication professionnelle par le trichloronaphthalene. Ann de med. legale, 14, 422 (1934). Abstr. of paper by Tooraine, A., and Mntrel, B.: Der matoses professionnelles par le naphthaline et ses derives. Prat, med. franc., 15, 335 (1934). 6. Schwartz, L.: Dermatitis from synthetic resins and waxes. Am. J. Pub. Health, 18, 5S6 (1936). -x^iF/dust surv "V-4gg*.- JaiSlSimpmger 3fg)by the L i'f-ir?. Service a . awiffiA cepted sf concentra (2), rritfev other mV' .',`idsLSi correlate 'AK^unpingeir Asii-v.; those of ^^'pinger. i lizS-Vi mvestigal :.z~ considere instrumei the dust j "counts" : Green lis formatter rivvi.. "the app h... sile stres vVfG ' the large cracking AiVi ' the mate ,-hC; (5) were any dcfii Jiagy this frac : * Recoi 1933. WATER_PCB-SD0000032510