Document JrZBKnzY76jvw1w2xmjoN04XK

difficulty with some of the terms. chapter it would have been well to the difference in general between .nd chronic effects,' as with many ees there is little similarity and the effect is usually the"more serious, i subject of workmen's compensation dace in a book on industrial health, velopment of occupational disease won should have been mentioned. .'0 general types of occupational discts (all-inclusive, and specific) with advantages or disadvantages are a paragraph or two. chapter on "First-Aid Treatment of =s" treats only the traumatic inBurns are taken care of in another :r, but under first-aid a few words have been helpful describing what to acute cases of poisoning, cyanide, i spills, etc., where the patient is still ling but where prompt action is necea- ' ' ' 1 r oes combine in one compact volume i a readable style much information ustrial safety and health that otherwould require reference to many a. For the beginning students of inal engineering, industrial safety and i, or personnel relations, it should a helpful book. The operating ;er and manager will want more cominformation on the particular expoin his plant and the industrial ;ian, if interested in prevention, will more on the engineering methods of rl.--5. TV. Gurney. *' ; : ? * i i " .trial canceb. By E. IF. Baader, 'Keck EKGEBNISSE AUF UEU GEB1ETE . krebskbakkheitsn". Adam and er, Leipzig, 1937 (pp. 104-J2S). aluable study, including the history dustrial cancer. Less well known of industrial cancer are included: the wd nasal cancers seen in England in 1workers, the lung cancers of generaorkera in Japan, and the liver cancer lers in the Curiscbe Haff, caused by ecb, 0 pittorchit felineus.--L. Ttleky. .; : ' ) .* * \ j THE JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY Volume 21 FEBRUARY, 1939 ' Number 2 me SYSTEMIC EFFECTS RESULTING FROM EXPOSURE TO CERTAIN CHLORINATED HYDROCARBONS* Leonard G reenburg, M ay R . M ayers and Adelaide R oss Smith .Ditijsfon of Industrial Hygiene, Hew York Slate Department of Labor, Hew York City CHLORINATED naphthalenes and diphenyls, because of their electrical, heat and moistureresisting properties, and because they axe non-inflammable, are used exten sively for insulating wire and in the product is present. On the whole, the higher the chlorination, the more toxic this material becomes. In the manufacture of chlorinated diphenyls, CiH is converted into CizH which, in turn, is chlorinated to C uCI; tbe manufacture of electrical condensers. substitution products range from the The chlorinated naphthalenes are monochlor to the decachlor diphenyl. naphthalenes in which one or more of A rather characteristic acneform the hydrogen atoms has been replaced skin eruption resulting from exposure by chlorine. There is, thus, a series to these substances has been recog of these substances beginning with nized for a great many years--indeed, monochlornaphthalene and going on ever since they began to be manu to the octochlor derivative. In in dustry they usually occur in mixtures in which more than one chlorinated factured about 25 years ago. -These skin eruptions came into some prom inence in Germany during the war and have been attracting sporadic interest 1938.' The chlorinated naphthalenes are eomc times referred to as " Halowax" by pur chascra and usera. While the Halowax Cor poration manufactures these substances `t also manufactures many others. Sinct the term "Halowax" is merely a trad name for substances manufactured by thii Company it should not be used indis criminately. In all instances, substancei ssahnoiuelsd obnely.designated by their chemical 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 medi cal practitioner is still somewhat un familiar withjthe skin eruptions, even 29 PLAINTIFF'S EXHIBIT 4356 906047 w H >/, TF.i M: 30 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [vol. tl, no. t though they are by no means uncom and (C) given off at 192C and 172C mon in the industries where the chlo respectively. Large 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- arid tetrachlornaphtha- 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 R eview of Literature on S ystemic E ffects* nated diphenyl were used. Briefly, these experiments showed, that the tri- and tetrachlornaphtha- 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 tetraehlornaphthalene, (B) a mixture of tetra- and penta-chlornaphthalene and (C) a mixture of penta- and hexa-chlornaphthalene. 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 festations appeared in the article by Mayers with necrosis of liver cells. and Silverberg mentioned above (1). It is of considerable interest that c: cl ra th X. Pc fa* ar* mt ap po tio pa po. bci to>. rin. stil abl ind 3 of! tioi 906048 192C and 172C doses, approx- rig, were injected day. ; compound (A) if compound (B) :ributable to these led at tbe end of. animals, however, " the higher chlo-' (B) and (C) and 0, all died in from utopsies uniformly mage. lant study to be of Drinker, Warren These investigachlorinated hydroion, subcutaneously i white rats. Mix1tctracblomaphthaand hexachlomaph(c) with 10% refined nyl; and (d) chlori de used. :xperiments showed, 1 tetrachlornaphtbalatively unimportant *ges in the liver until concentrations were xposed for 6 weeks to nations, however, in centrations, regularly grees of liver damage a group, they gave no es of such toxicity vposed to still higher the rats lost weight id began dying after 8 many with severe lunation of the liver Is at autopsy revealed d fatty degeneration f liver cells, siderable interest that the exposed rats, which gave no clini tion of the Labor Department in New 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-ohlorin- tetrachloride--a dose well tolerated by ated naphthalenes. After a long and control animals. serious illness, when the girl was on Two other points of interest were her way to recovery, the physician brought out by the study: (1) in the expressed the opinion that within a rats, which on autopsy showed even few weeks she would be able to return marked pathological lesions of the to her former work. Whatever tbe liver, no abnormalities were found in cause of the jaundice in this case, there 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 (2) even the less important patho grave risk to the patient's life. logical changes induced in the liver by In 1934, Courtois-Suffit (5) reported these chlorinated hydroerbons in the on the work of Touraine who, with lower concentrations were found to be his associates, examined 60 workers ex very persistent, being present even 2 posed to trichlornaphthalene and months after cessation of exposure. found mild digestive disturbances and Clinical Reports.-- Clinical reports of dizziness in 13, but nothing of a more cases of systemic poisoning from the serious nature. chlorinated naphthalenes are as yet In 1935, Schwartz suggested the rare in spite of the length of time that possibility of systemic disease from these substances have been in use. exposure to these substances in a talk No doubt the infrequency of such re before the American Public Health ports has been, in part, due first, to the Association (6). fact that cases of systemic poisoning In 1936, three fatal cases of jaun are unusual occurrences--the ele dice in chlorinated naphthalene work ment of individual susceptibility ers were recognized in this country. appearing to play an even more im- - These were reported by Flinn (3) and portant r61e than usual in this situa tion--and second, to failure on the part of physicians to recognize cases of poisoning. Until recently there has been general lack of knowledge of the toxicological properties of these chlo rinated hydrocarbons, and there is still relatively little information available regarding tbe clinical picture of industrial poisoning from them. The danger that lies in such a lack Drinker (4) who summarized the cases briefly. All three of the men were young and in none could any predisposing cause other than their industrial exposure be found to account for their illness. Two of tbe 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 exposed to a1mixture of tetra- and of knowledge is exemplified in a situa penta-cblomaphthalene with 10% tion that recently came to the atten chlorinated diphenyl. In both, the 906049 fM g| i 32 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY M - . "O. t 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 bad 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 H istories 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 Koss 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 Slate 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!. 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 thi3 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 graduated from grammar school she attended high school for 1year 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 she 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 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. Herc| 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, a t that time, was 100". A diffuse papulo-pustular 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.! From then on she suffered from j Investigation revealed the fact that some of her co-workers were also suffering from a similar neneform eruption, and one girl discontinued her work because of it. None of these other girls suffered any systemic disease. Feb. 19. incrcasi petite u sively n t on inc. Abou mother : J About 3 of sever abated, a puffine feet and She c< 1 week fc of admii moveme: tary bo: with an; seemed t change i the hosp: This war curred. state of r SuTTtm, patient colored p white. dcvelopec puffiness men. Sh quently contrctil ciated w bead. TJ ri4, respi: The fir Uent is s More can neck reve: tion begin down Besides t were three rest, appe; coal--one ne on tl these blaci of uggregs d>d not sh: tion. l t T teristic of The skin of the bod; iah aubtini 906050 y j r,4,1!. >Af. Vr r r SYSTEMIC EFFECTS OF CHLORINATED HYDROCARBONS a April 26 ,,::un. She was ... t .-i`.'ioa. . . . ..blained from _ * , J iitlirely ncga.. , ;..jL'i1lectomy in . -*.f |ircacnt illness .ilihy and free I v-^fT as as follows: Btraniinar school --.: (l year and then . l-. with a concern ..... -..iuJcnsers for use . --i : ;;.Uone place for . * -king there 7 days . .> ir.i hospital. soldering and -- .) possible, from i she may also - l sz operations, but > ascertained. .luting of the con-- : t-i the fumes of tri- if with which the r-_lly impregnated. m *, *-* *j exposed to fumes ssphthalenes from conducted In close -- <s', which the solder- rrsn about 5 months -- . hospital--or ap- *t'-.er starting work in at -- '***-- > ,j,f notice(l several * '_l '* ^ r face. These con- l*-. ^ 'verity and extent, '" " ,:l the outpatient de- in Hospital. Herei " ^ r urine and she was *&***n^ " * ^ ere a diagnosis was made. Her 1__11that time, was 100. ^ -*r eruption was also - * On being questioned l-11**`-*ted that it had been 'fdge for about 2 'a on she suffered from the fact that *'* *erc also suffering eruption, and one u*; because of it. prla- sufiered any increasing weakness and nausea. Her ap petite was poor; her skin became progres sively more jaundiced, and tbe pigmenta tion increased. About 6. weeks before admission her mother noticed that her eyes were yellow. About 3 weeks later she began to complain of severe headaches which continued un abated. This was followed in a few days by a puffiness and swelling of the face, hands, feet and abdomen. She continued at her regular work until 1 week before admission. On tbe morning of admission she began to have convulsive movements of the abdomen with involun tary 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 the hospital in the ambulance she vomited. This was the first time vomiting had oc curred. She arrived in the hospital in a state of prostration. Summary of physical examination.--The patient gave the impression of being a colored girl although she was, in reality, white. She looked well nourished and well developed for her age. There was general puffiness of the face, hands, feet and abdo men. She was hiccoughing, and was fre quently disturbed by a series of tetanic contractions of the abdominal muscles asso ciated with involuntary bobbing of the head. The temperature was 100, pulse 114, respiration 26. The first admission note stated, "pa tient is so jaundiced her face is black." More careful examination of the face and neck revealed a negroid type of pigmenta tion beginning at the hair line and extend ing down to, and including, the neck. Besides this general pigmentation there were three areas somewhat darker than the rest, appearing very much like dabs of char coal--one on each cheek below the eyes and ne on the chin. On close examination these black spots appeared to be the result aggregations of comedones. The scalp did not share in the general dark pigmentation. ft was of a yellowish color charac teristic of jaundice. The skin of the thorax and the lower part f the body was dark brown with a yellow- i*h subtinge. Over tbe skin of the abdo 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 tbe 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 sclerae and the conjunct tivae. 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 exophthalmuB. 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 tbe feet and hands; an apical systolic murmur; abdomen distended and tympani tic; liver on percussion 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,6.9mg./100 cc.; Urea N. 20.S3 mg./lOO cc., Creatinin, 2 mg./lOO cc.; Glucose, 88 mg./lOO ee.; Cho lesterol, 145mg./lOO cc.; Calcium, 8 mg./100 cc.; CO combining power, 52; Albumin, 2.5 mg./lOO cc.; Icteric index, 230; Van den Berg, immediate direct reaction; Wassertnan, negative. Urine--Sp. gr. 1.008: Alkaline. Albu min negative. Sugar, a trace. Acetone, 1+. 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--'So evidences of lesions of the heart and lungs; bones of skull, ribs, shoulder joints, clavicles, tibia and fibula. The gastric contents, and later, 906051 S g sa fs& a t-.' l r t g l g ?.v g y , ?. i' i ; . f e i -V3 $ fij PP W m ., : ,^ |i :: m g ffeg & g - 2 vJv''K* b '3 fl w 34 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [m!. ti, no. t at autopsy, the organs were analyzed for Body opened in usual midline incision. arsenic, phosphate, lead, tin and antimony, Sternum removed. Some remnants of thy A trace of phosphate was reported, prob mus still present. LuDgs are free. Bron ably from inorganic phosphates ingested chi contain a bloody mucous. Mucosa before admission. injected, has yellowish tinge. Hemor Diagnosis--The patient presented a pic rhagic infarct about size of hen's egg in ture which was distinctly puzzling to all left lower lobe. This is airless and dark physicians who saw her and no conclusive red in color, firm. There are also similar diagnosis was reached at the time. The smaller areas in other lobes. Heart is small various diagnoses suggested included: ob and shows some sub-epicardial hemor struction of the common bile duct, toxic rhages. Some hypertrophy of left ventri jaundice possibly due to some dye, obstruc cle. Valves thinned. Arteries natural. tion of the inferior Vena Cava, blood dys- All are bile stained. No significant findings crasia, Addison's diabetes, hemochro in myocardium or coronary arteries. matosis, industrial poisoning of unknown Esophagus is natural. Stomach is dis origin possibly due to arsenic, causing acute tended, contains some dark material. The glomerular nephritis and acute hepatitis; rugae are somewhat hypertrophied. The and finally acute yellow atrophy of the liver duodenum contains green chyme. The and pancreas possibly due to an unknown ampulla is patent. The jejunum, ileum and industrial poison. large gut are natural. Many petechial Course--The clinical course was steadily hemorrhagic areas noted in the mesentery down-hill. At 11 p.m. on April 27th the with some enlargement of mesenteric lymph patient became unconscious and went into nodes. a coma. There was Cheync-Stokes breath Liver is small, weight 720 gm. Capsule ing. A peculiar odor was present which was wrinkled. Right lobe on section shows variously identified by hospital physicians areas of yellow surrounded by red areas. as ethylene or garlic. The pupils were im Left lobe much firmer although liver cuts mobile to light. Deep reflexes were greatly firmly throughout. All ducts patent. Gall depressed. There was no Babinski. Ab bladder small. Wall thickened throughout. dominal reflexes disappeared. The skin Pancreas is natural in size, somewhat became dusky throughout. The liver dull congested. Spleen is natural in size. On ness seemed to diminish. On April 28th section, firm, dark red in color. Follicles the temperature rose to 106*; the pulse to are somewhat indistinct. Kidneys show 140, and the patient died. swollen cortex. Evidence of parenchyma Anatomical diagnosis--An autopsy was tous degeneration of epithelial cells. performed at the Medical Examiner's office Capsule strips easily. No granulation. on April 29, by Dr. Chas. H. Hochman, Degenerative changes in cells of glomeruli Assistant Medical Examiner. The report only. No glomerulitis. Uterus is small. in full was as follows: Endometrium bile-stained. Ovanes arc Body is that of a white adult female, well natural in size; right contains corpus lu- developed and nourished. Cyanosis of lips, teum cyst. Bladder wall is somewhat ears and fingernails. Marked pigmentation thickened. Mucosa is injected. about eyes, lower lips, neck and abdomen. Microscopie examination--Liver--From General icteric tinge to entire body. No size of a through and through transverse evidence of violence. Some edema about section one suspects that the entire liver ankles. Hair is black. Eyebrows black. was about j normal size. Liver segment Brown iris. Conjunctivae and sclerae ic is very firm and composed of two distinct teric. Rigor mortis present. Postmortem and peculiar types of tissue: (a} That con lividily of dependent parts. Scalp incised stituting major portion of parenchyma is and reflected, calvarium removed. Brain red in color; firm and elastic in consistency; found congested. Meninges bile tinged. (b) Other areas are light yellow in color and On section, no evidence of intracranial in are scattered indiscriminately throughout jury or hemorrhage. Dura stripped and reddish areas, Yellow areas_ vary from reveals no evidence of fracture. 1 to 2 in. in diameter. External surface Ftl of sm' low red atr< dis: the' Beei bio. and nun seer yell gen- T of t port due The rege seen Acs. ing _ proc S cori Som deej E royo K erat' glon glon A dege P. of ct S: dent volv liver and SIUJi A mitt 2. 19 tory B 906052 OGY [vol. tl, no. I uni midtine incision, jme remnants oi thyings are free. Bron|y mucous. Mucosa vish tinge. Hemorsize of hen's egg in. j is airless and dark 'here are also similarlobes. Heart is small, lb-epicordial heraor:rophy of left ventri1. Arteries natural. So significant findings ronary arteries, iral. Stomach is disc dark material. The hypertrophied. The green chyme. The 'hejejunum, ileum and ral. Many petechial ted in the mesentery it of mesenteric lymph gilt 720 gm. Capsule be on section shows unded by red areas, ner although liver cuts Ml ducts patent. Gall thickened throughout, ral in size, somewhat s natural in size. On *ed in color. Follicles itinct. Kidneys show dence of parencbyma- of epithelial cells, ily. No granulation, is in cellB of glomeruli itis. Uterus is small, stained. Ovaries are at contains corpus lu;r wail is somewhat is injected. firnation--Liver--From nd through transverse s that the entire liver l size. Liver segment nposed of two distinct if tissue: (a) That con ation of parenchyma is d clastic in consistency; ight yellow in color and :riminately throughout How areas vary from :lcr. External surface Feb. 193$) SYSTEMIC EFFECTS OF CHLORINATED HYDROCARBONS 35 of liver, judging from this portion, was smooth. A typical picture of clear subacute yel low atrophy is revealed. Slides show that red area is. composed of so-called "red atrophy" in which all the liver cells have disappeared, their place being occupied by their normal supporting stroma, which seems to have been spared, great numbers of blood cells, early fibroblastic proliferation and older scar tissue. In these red areas, numerous bile ducts are seen. These also seem to have been spared destruction. The yellow areas are composed of actively re generating islands of liver cells. The toxin evidently has destroyed most of the liver cells, leaving intact their sup porting stroma, blood vessels and bile duets. The latter Beem to be regenerated. Those liver cells Bpared destruction have regenerated and have formed yellow islands seen in the gross picture. There evidently has been one or more attacks of fiepaiiiij judg ing from the different ages of the pathological process in various parts of liver.* Skin--Shows an increased density of cerium which stains deeply with eosin. Some of the epidermal cells are slightly deeper in corium than normal. Heart--Shows mild parenchymatous myocardial degeneration. Kidneys--Show Bevere epithelial degen eration involving epithelium of tubules and glomeruli. No inflammatory reaction of glomeruli. Adrenals--Show severe parenchymatous degeneration of cells. Pancreas--Shows intense degeneration of cells of acini and of islets. Summary--An unknown toxin has evi dently caused a severe diffuse eytolysis in volving most of organs, predominately the liver. The latter has evidently undergone and recovered from previous attacks of a similar nature.* Case S--F. D. A young man, 24 years of age, was ad mitted to the New Haven Hospital on May 2, 1934, complaining of jaundice. The his tory given was as follows: He had worked in a wire factory coating * Authors' italics. wire with wax| from July to the middle of December, 1933. At th at time he felt run down and became jaundiced. He was seen in the dispensary in January and found to have an enlarged palpable liver. He then spent several weeks in another hospital with slight improvement in the jaundice. In March, 1934, he returned to the job in the wire factory. Following this, the jaundice became quite intense with increase in general malaise, anorexia, attacks of dizziness and loss of weight. Three days before admission vomiting had occurred. He had taken no drugs and there had been no exposure to carbon tetrachloride or chloroform. Summary of physical examination--The temperature was 99, pulse 74, respiration 20, blood pressure 130/74. The patient was a thin well-deveioped' man who appeared moderately ill. There was bright yellow jaundice of the entire body. The pupils were widely dilated, the nasal septum de viated, causing obstruction on the right, the mucous membranes injected and the tongue moderately coated. The tonsils were enlarged and cryptic. Lungs were clear, heart normal, radial vessels soft, abdomen tympanitic, soft non-tender. The liver edge was felt at the costal margin. The organ was soft and non-tender. The upper edge of the liver dullness was in the 6tb interspace. Laboratory findings--These were as fol lows: Urine--was dark yellow and was nega tive except for the presence of bile and uro bilin. Blood count--red cells, 4,360,000; hemo globin, 85%; white cells, 6,800; Polys., 65%; Lymphs, 29%; Large Monos., 4%; Eos., 2%. Subsequent examinations showed a slight rise in white cells to 10,000. ' Btool--showed bile, considerable undi gested food, small amount of fat. Kahn test--negative. LiVer function tests--Icteric index--30 to 50. Bromsulfonphthalein showed marked t The waxes employed in this process are the higher chlorinated naphthalenes. These are used in a molten state in a bath through which the wire to be coated is passed. The process is partially but sot entirely enclosed. Exhaust ventilation is in use. _ %U 906053 MSict: fe ser. ,,j * JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY Icol. 11, no. 1 impairment: 100% retention in 5 min., pneumonia (bilateral), subpleural hemor 85% retention in 30 min. rhages, cloudy swelling of kidneys. Blood chemistry: Non-protein nitrogen, 28 mg./100 ee.; Urea N, 11 mg./100 ce.; Case 3--C. C. Serum total proteins, 6.15 mg./lOO ee.; Serum total albumin, 2.66 mg./100 cc.; A young man 22 years of age was admitted to the New Haven Hospital on February 28, Scrum total globulin, 3.19 mg./lOO ee. 1935 with the complainta of jaundice, ab A/G ratio, 0.76; Blood sugar, 68.0 mg./100 dominal pain, nausea and vomiting of ee.; Blood calcium, 10.32 mg/100 ee.; bloody material. The bistory given was as Blood phosphorus, 1.12 mg./lOO cc.; Serum follows: fatty acids, 11.3 mg./lOO cc.; Serum lipoid phosphorus, 7.5 mg./lOO cc.; Serum total cholesterol, 10.5 mg./lOO ce.; Serum free He had worked in the same wire coating plant as the previous patient (F. D.). The present illness had begun with jaundice 2 cholesterol, 63.0 mg./lOO. Sugar tolerance-Ust vas within normal months previously with no other symptoms. This continued for about 1} months. limits. Two weeks before admission be became X-ray of abdomen showed hepatic flexure of colon unusually high. more jaundiced and concomitantly de veloped upper abdominal pain, malaise, Course. The patient was put on a high nausea and finally vomiting--the vomitus carbohydrate diet and hia general condition becoming bloody in character. He was improved hut the jaundice persisted. He treated by bis family doctor with no relief. was discharged on May 16, 1931 with the His condition became worse and he finally diagnosis of toxic hepatitis. He was admitted again on June 1, 1931 complaining of abdominal swelling of 3 became delirious and incoherent. Hos pitalisation was advised. Summary of physical examination--The days' duration, weakness, anorexia and edema of the legs which had developed soon patient was comatose, irrational and vomit ing bloody material. Positive findings of after bis discharge. The physical exam significance were as follows: Temperature ination showed deep jaundice, systolic mur mur, abdomen distended and tympanitic not elevated. Blood pressure 102/68. Generalized jaundice, petechiae over the with dullness in the flanks, moderate pitting extensor surfaces of the arms; tenderness edema of the legs. Examinations of tha urine, blood and stool showed no important variations from the original findings with the exception of a drop in white cell count to 6,1D0 with 71% polys., and a decrease in serum albumin to 1.88%. Serum COt con tent was 51.51. Serum chloride was S8.0 mg./lOO cc. The patient's course after the second admission was rapidly downhill. The dis tention could not he controlled and he soon passed into complete coma. A convulsion occurred on June 8th and on June 10th he died. 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 21 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. Anatomical diagnosis.* Extensive nec rosis, fibrosis and regeneration of liver, DISCUSSION acuto entero-colitis with edema, fibrosis of These three cases show the occur psnerens, acute pancreatitis, jaundice, ns- rence of similar pathological changes in citea, edema of lower extremities, focal the liver in three young adults known Autopsies ou this and the following case were performed on the pathological service to have been working with chlorinated of the New Haven Hospital by Dr. H. M. naphthalenes and diphenyls--all were Zimmerman. Grateful acknowledgement is made of hia courtesy in permitting use of exposed directly or indirectly to the the reeorda. higher chlorinated hydrocarbons. In 906054 . ..y >fll. , no. < bemor- f ^ . l4 i tiJneyi. ** . ..inFebruary28, 4 ... -f jaundice, ftb- r.d vomiCiog of . ivjtv given wns m 4tw .T.fwire coating * i**- 51(F. D.). The W *-o`. wiib jaundice 2 - >i mothersymptoms. ut 1) months, r be become ' i - afimiitsntly de; -d pain, malaise, -..tics--the vomitus rsettr. He was . . - w with no relief, i^---- * * and he finally -i ;coherent. Hos.. * -- b-ceminah'tm--The *-1*.tonal and vomit- -.live findings of ** ` : Temperature --* leisure 102/68. - - :*.(thiae over the arms; tenderness fc**tai*"l the abdomen. -- =-ablt. -- -*_-n l*time rapidly '* aafter admission. The patient died "* i'jion. - httensive necro* ' " " l '* 1,ver; jaundice, " ' "''rtsl nodes; as* '* ,`*junum; cloudy _*"*ydneri; acute pulirsnthematous " Mios ^1 :^ '*-- ry-- *',ow the occurchanges in adults known chlorinated 'l^cnyls--all were inMeetly t 0 the "I'drocarbons. In Fib. 15591 SYSTEMIC EFFECTS OF CHLORINATED HYDROCARBONS 37 all three cases, a most careful investi larly exposed occurs only in those gation failed to reveal any other pre having some pre-existing substratum disposing cause for the condition. In of liver damage--such as might follow the first case in particular, that of & an attack of catarrhal jaundice, for healthy young girl on her first job, example--and that this m ight ac the absence of any conditions predis count, in part at least, for the fact posing to liver damage either preced that only a very occasional worker out ing or following her exposure to the of a large group will suffer from sys substances in question is especially temic effects of exposure to these sub clear. stances. In the three cases reported It is of interest to note that two of however, no history was given sug the cases apparently had suffered from gesting that any hepatic disorder prior at least one previous attack of hepati to exposure had occurred. tis followed by a certain degree of The presence of a papulo-pustular improvement before the onset of the eruption in two cases is of interest. fatal attack. In one it antedated the systemic sym p In view of the fact that Drinker, toms. This type of eruption is char Warren and Bennett* found no lesions acteristic of the dermatitis caused b y in organs other than the liver in their chlorinated naphthalenes, and until experimental animals, it is noteworthy recently was the only disturbance at that such lesions were conspicuous in tributed to them. all three of the cases here reported. The presence of "aggregations of Such lesions, are, indeed, usual find comedones" such as were found in ings in cases of acute yellow atrophy Case I is also characteristic of the of the liver in humans regardless of skin eruptions produced by these sub etiology. On the basis of present stances. The question as to whether knowledge, it would be impossible to or not the skin eruption in such a case say whether they are the result of is in any way connected with the onset primary intoxication or are merely of systemic effects cannot be answered, secondary to liver damage. In the since thus far no correlation has been light of the animal experiments, how established between skin lesions and ever, one would incline to the latter systemic disease (1). view and speculate as to the part It is interesting, therefore, that in played by length of exposure, in the Case I the skin eruption apparently final pathological picture. antedated all evidences of systemic It has been mentioned that in disease. Had the girl been promptly Drinker's (4) experiments, rats with removed from further exposure, when no evidence of clinical disease while it was first observed, it is possible that being exposed to the chlorinated naph her life would have been saved; or had thalenes, promptly died from acute the physicians first called upon to yellow atrophy of the liver when given treat the jaundice (of whatever origin) doses of carbon tetrachloride so small in her case, or in the second case here ss to be harmless to control animals. reported, recognized the danger of This prompts speculation as to continuing exposure to the chlorinated whether death from acute yellow naphthalenes, these deaths might pos atrophy of the liver in workers simi sibly have been averted. :-L_ 906055 tool, 21, no. 2 persons, should not be further exposed in their work to potential liver poisons. 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 which have been carefully worked up, so that the clinical disease entities resulting from such exposure can become further clarified and thus more 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 ibis 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 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. Summary workers with a history of typhoid fever, malaria, gall-stones or other dis eases known to affect the liver ad versely. The systemic effects resulting from exposure to certain chlorinated naph thalenes are discussed, and the litera ture of the subject briefly summarized. 4. Persons receiving arsphenamine Three liver deaths in workers handling treatment fo i syphilis; or those who these substances are presented in some are taking drugs believed to be in detail, with autopsy findings. Recom jurious to the liver in susceptible1234 mendations for prevention are given. BIBLIOGRAPHY 1. Maters, M. R., and Silverberg, M. Q.: Skin conditions resulting from expo sure to certain chlorinated hydro carbon. T ris J., to, 244 (1938). 2. Lermann, K. B.: Kurie Lehrbuch der Arbeite- und Gewerbehygiene. S. Hiriel, Leipzig, 19X9. p. 251. 3. Flinn, F, B., and Jaryie, D. E .: Action of certain chlorinated naphthalenes on the liver. Proc. Soc. Exper. Biol, and Med., SB, US (1936). 4. Dbineer, C. K., Warren, M. F., and Bennett, G. A.; The problem of potlible systemic effects from certain chlorinated hydrocarbons. T bis J., 19, 283 (1937). 5. Courtois-Sufeit: tude aur l'intoxication professionnelle par le trichloronaphthalene. Ann de med. legale, 14, 422 (1934). Abstr. of paper by Toobaine, A., and Mntrel, B.: Der matoses professionnelles par le * naphthaline et ses drivs. Prat, med. franc., 15, 335 (1934). 6. Scbwartz, L.: Dermatitis from synthetic resins and waxes. Am. J. Pub. Health, 29, 6S5 (1936). IT fV / ini] ititi. liiy ini] l<y ."Vr '``P mi lii-l. ulh' ii in ini), fluir pini itivi filli: ilist (he "fUI Onfuri: `111. mili tili. iTili f tu fo) iUIV Ibis * iurta L 906056