Document 44eZZeJ6gOrpD3B93Qnrq9eRa
28 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY [vol. SI, no. I
engineers and contractors, as well as by young men who arc turning to this industry for employment.--LiE. Silverman.
a little difficulty wjth some of the terms. In this chapter iFwohld have been well to explain the difjmrencclin general between acute and ch/onic effn cts, as with many
Industrial IIyciienb. By L. B. Clwnowctli and IF. Mac.hle. Cloth. Pp. 221. F. S.
substances t/crc is littl ; similarity and the chronic effafit is usually the more serious.
Crofts & Company, New York, 1938
If the subject of work nen's compensation
(Price $2.00).
The chapter handings give a good sum mary of what thif authors of this hook have
has a place in a book on industrial health, the deyt-lopnient of okccupational disease Icgislnnon should ha\J( been mentioned.
attempted to c<wer. These are:--
The two general typesjof occupational dis
1. Historical introduction, 2. Workmen's ease/acts (all-inclusive and specific) with
Compensation,(3. Industrial Accidents, 4. the/r advantages or disadvantages are
Fatigue, 5. Physical Factors in Industrial Hygiene, 0. Ijeulth Service in Industry,
worth a paragraph or/two. /The chapter on "First-Aid Treatment of
7. First-Aid (Treatment of Injuries, 8. Injuries" treats onliy the traumatic inOccupational / Intoxication, 9. Chemical ijuries. Burns are taken care of in another
Burns, 10. Oxygen Deficiency and As-, chapter, but under Ifirst-aid a few words
phyxia, 11. Dust Diseases, 12. Respirators/ Gas Masks, lind Breathing Apparatus, 13 Occupational Affections of the Skin, PL Industrial Neuroses and Malingering, /15. Miscellaneous Occupational Affections,
would have been helpful describing what to
do in aeute cases |>f poisoning, eynnide,
aniline spills, etc., where the patient is still
breathing but wheraprompt action is neces
sary.
I
with nppenf lices on Bandaging, Splicing, Rescue in Asphyxiation, Methods of/Artifieinl Resp rntion, and Transportation of the Injurei
This pretr nts a wide range of subject material to eo< cr in any one book, altl/ough the authors' dr ire to show the relationships of all of these subjects to industrial health is understandable. In general, occupational
hygiene is tluiught of as concerned with the
It does combine n one compact volume and in a readable jityle much information on industrial safety nnd health that otherwise would requi 3 reference to many sources. For the 1 eginning students of in dustrial enginecrini industrial safety and health, or persom|e relations, it should prove a helpful book. The operating engineer and mana ;er will want more com plete information m the particular expo
industrial disuses, their caus/s, effects and methods of cdhtrol or climiuinion, although there is probably no good rouson why trau matic injuries\ with their/prevention and
sures m his plant and the industrial physician, if interested in prevention, will want more on the engineering methods of control,--S. IF.
treatment shouM not be included as well. The chapter c\titled/'Oeeupational In
toxication" (the IfiTTgest chapter in the book) departs from the usual grouping of toxic substances by their effects (irritants, asphyxiants, drug-like substances, etc.,) and lists by a possibly more chcmicnlly jus tified grouping gaseous elements, nonmctallic, light metallic, heavy metallic, and
Industrial, cancer. By E. IF. Baadcr, in "NeUE ERCEIINI8SE AUP DEM GEI1IETE der krerskranksieiten". Adam and Auler, Leipzig, 1937 (pp. 104-128). A valuable study, including the history
of industrial cancer. Less well known forma of industrial cancer are included: the lung and nasnl cancers seen in England in nickel workers, the lung cancers of genera
organic with appropriate chemical sub tor workers in Japan, and the liver cancer
groups. This arrangement is more useful of fishers in the Curischc Haff, caused by
for reference. The non-chemist may have the leech, Opislorelns felineus.--L. Tclcky.
THE JOURNAL OF INDUSTRIAL HYGIENE
AND TOXICOLOGY
Volume 21
FEBRUARY, 1939
Number 2
THE SYSTEMIC EFFECTS RESULTING FROM EXPOSURE TO CERTAIN CHLORINATED HYDROCARBONS*
Leonard Greenburg, May R. Mayers and Adelaide Ross Smith
Division of Industrial Hygiene, New York Stale, Department of Labor. New York Ci(o
HLORINATED naphthalenes product is present. On the whole,
C and diphenyls, because of their electrical, heat and moisture-
the higher the chlorination, the more toxic this material becomes. In the
resisting properties, and because thmeaynufacture of chlorinated diphenyls,
are non-inflammable, are used exten CH6 is converted into C^Hio which, in
sively for insulating wire and in the turn, is chlorinated to C12CLo; the
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 the hydrogen atoms has been replaced by chlorine. There is, thus, a scries of these substances beginning with monoehlornaphthalene and going on to the oetochlor derivative. In in dustry they usually occur in mixtures in which more than one chlorinated
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.
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 bo used indis criminately. In all instances, substances should bo designated by their chemical names 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 medi cal practitioner is still somewhat un familiar with the skin eruptions, even
WATER PCB-00054552
So ,JOURNAL OK INDUSTRIAL HYGIENE AND TOXICOLOGY M. 21, no. 2
though they are by no means uncom mon in the industries where the chlo rinated naphthalenes and diphenyls arc used. The reason for this is that any one physician is likely to sec such eases only rarely, unless he happens to be practicing in the immediate vi cinity of one of these factories where large numbers of workers are em ployed. 'That the relatively rare sys temic effects resulting from such exposure almost invariably go un recognized is not surprising under the circumstances. It is of the greatest importance however, that physicians become acquainted as promptly as pos sible with the clinical and pathological pictures -presented by these patients, particularly as regards systemic ef fects, since failure to detect early clinical manifestations of toxicity, and to remove susceptible individuals promptly from further exposure, may, on occasion, result fatally.
liming .01 Liteiutuke ox Systemic Effects*
and (C) given off at 192C and 172C respectively. Large doses, approx imately 15 mg. per kg, were injected subcutaneously each day.
Animals receiving compound (A) and the sublimate of compound (B) showed no lesions attributable to these substances when killed at the end of 2 months. 'The 30 animals, however, which had received the higher chlo rinated compounds (B) and (C) and the sublimate of (C), all died in from 12 to 2G days. Autopsies uniformly showed extensive damage.
The next important study to be published was that of Drinker, Warren and Bennett (4). These investiga tors administered chlorinated hydro carbons by inhalation, subcutaneously and by mouth, to white rats. Mix tures of (a) tri- and tetrachlornaphthalene; (b) penta- and hcxachlornaphthalcne alone, and (e) with 10% refined chlorinated diphenyl; and (d) chlori nated diphenyl were used.
Briefly, these experiments showed, that the tri- and telrachlornapbtha-
Experimental studies.-- The first lencs 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). lie used. Animals exposed for G 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, I'Tinn and Jnrvik (3) ex clinical evidences of such toxicity
perimented on rabbits with three dif while ulivc, Exposed to still higher
ferent compounds; (A) a mixture of concentrations, the rats lost weight
tri- and tctrachloruaphthulene, (B) and appetite, and began dying after 8
a mixture of tetra- and penta-chlor- days' exposure-- many with severe
naphthalenc and ((') a mixture of penta- and hexa-ohlornnphthalene. They also used sublimates of (R)
jaundice. Examination of the liver of these animals at autopsy revealed marked central fatty degeneration
* A review of 1110 literature on skin mani festations appeared in the artiele by Mayers and Silvcrborg mentioned above (1).
with necrosis of liver cells. It is of considerable interest that
Feb. 1039] SYSTEMIC EFFECTS OF CHLORINATED HYDROCARBONS
31
the exposed rats, which gave no clini cal evidences of disease, promptly died from acute yellow atrophy of the liver when given a very small dose of carbon tetrachloride--a dose well tolerated by control animals.
Two other points of interest were brought out by the study: (1) in the rats, which on autopsy showed even marked pathological lesions of the liver, no abnormalities were found in the other organs--a finding not un common in experiments on animals, but rather rare in humans who die from acute yellow atrophy of the liver; (2) even the less important patho logical changes induced in the liver by these chlorinated hydroerbons in the lower concentrations were found to be very persistent, being present even 2 months after cessation of exposure.
Clinical Reports.--Clinical reports of eases of systemic poisoning from the chlorinated naphthalenes are as yet rare in spite of the length of time that -_thc.se substances have, been in use. No doubt the infrequency of such re ports has been, in part, due first, to the fact that cases of systemic poisoning arc unusual occurrences--the ele ment of individual susceptibility appearing to play an even more im portant rble than usual in this situa tion--and second, to failure on the part of physicians to recognize eases 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 avail
able regarding the clinical picture of industrial poisoning from them.
'The danger that lies in such a lack of knowledge is exemplified in a situa tion that recently came to the atten
tion of the Labor Depart incut in New York State, in which a physician had been treating a severe case of jaundice in a young woman exposed to chlorin ated naphthalenes. After a long and serious illness, when the girl was on her way to recovery, the physician expressed the opinion that within a few weeks she would be able to return to her former work. Whatever the cause of the jaundice in this case, there is good reason to believe, on the basis of the experimental work previously cited, that further exposure to such substances would have entailed a grave risk to the patient's life.
In 1934, Courtois-Suffit (5) reported on the work of Tourainc who, with his associates, examined 60 workers ex posed to trichlornaphthalcnc and found mild digestive disturbances and dizziness in 13, but nothing of a more serious nature.
In 1935, Schwartz suggested the possibility of systemic disease from exposure to .these substances in a talk before the American Public Health Association (6).
In 1936, three fatal cases of jaun dice in chlorinated naphthalene work ers were recognized in this country. These were reported by Flinn (3) and 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 the men who had worked side by side died within 2 months of each other. Both had been exposed to mixtures of penta- and licxachlornaphthalene, and one had been exposed to a mixture of tetra- and pcnta-chlornaphthalcne with 10% chlorinated diphenyl. In both, the
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 eases of non-fatal jaundice among indi viduals with similar exposure. No details are given.
Case IIistohieb
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 hepaloxic 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 ease was, seen iii 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 Grecnburg, (now Execu tive Director of the Division of In dustrial Hygiene of the New York Stale 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.
Case 1. U. F*
A 17 year old girl was admitted to the Lincoln Hospital, New York City, on the
* (baleful 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 ease.
service of Drs, Kenneth Taylor, Edwin Hauser and Scott Johnson on April 20, 1032 in a scmi-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 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 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 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. 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 reetul temperature, at that time, was 100. A cliff use 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.f From then on she suffered from
| Investigation revealed the faet 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.
increasing weakness and nausea. Her ap petite was poor; her skin became progres sively more jaundiced, and the pigmenta tion increased.
About C weeks beforo 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 beforo admission. On the morning of admission she began to bave 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 puflincss of the face, hands, feet and abdo men. She was hiccoughing, and was fre quently disturbed by a scries 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 one on the chin. On close examination these black spots appeared to be the result of aggregations of comedones. The scalp did not share in the general dark pigmenta tion. It was of a yellowish color charac teristic of jaundice.
The skin of the thorax and the lower part of the body wns dark brown with a yellow ish subtingc. Over the 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 aline 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 sclerne and the conjunctivae. The pupils were equal and regular, and reacted to light and accommodation. There was no nystagmus or strabismus. The blephora! conjunct!vac 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 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./]00 cc.; Protein, 6.9 mg./l00 cc.; Urea N. 20.83 mg./lOO ec., Creatinin, 2 mg./lOO ec.; Glucose, 88 mg./lOO ec.; Cho lesterol, 145 mg./lOO ec,; Calcium, 8 mg./lOO cc.; CO combining power, 52; Albumin, 2.5 mg,/100 cc.; Icterie index, 230; Van den Berg, immediate direct reaction; Wasscrman, 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--No evidences of lesions of the heart and lungs; bones of skull, ribs, shoulder joints, clavicles, tibia and fibula. The gastric contents, and Inter,
Ut
, t i .1
\\rlr all..! \ /.'ll lor
arsenic, phosphate, lead, tin mid antimony.
A truce: of phosphate was reported, prob-
uhly 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 dys-
crasin, Addison's diabetes, hemochro
matosis, industrial poisoning of unknown
origin possibly due to arsenic, causing acute
glomerular nephritis and acute hepatitis;
and finally acute yellow atrophy of t he 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 Chcylie-,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 redoxes were greatly
depressed. There was no llnbinski. Ab
dominal reflexes disappeared. The akin
became dusky throughout. The liver dull
ness seemed to diminish. On April 28th
the temperature rose to 100; the pulse to
141), and the patient died.
Anatomical diagnosis -- Aw autopsy was
performed a a the Medical Examiner's office
on April 21), by Dr. Clms. 11. Hoehmun,
Assistant Medical Examiner, 'flic report
in full was as follows;
llody 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.
Drown iris. Conjunctivac and sclcrae ic
teric. lligor mortis present. Postmortem
lividitv of dependent parts. Sculp incised
and reflected, calvarium removed, Drain
found congested. Meninges bile tinged.
On section, no evidence of intracranial in
jury or hemorrhage. Dura stripped and
reveals no evidence of fracture.
I ,.,,|\ O pi >n 1 t n, u I.... 11.11 i. .. > H.'i-e ill.
Sternum removed. .Some remnants of thy mus still present. Dungs 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 eolor, firm. There are also similar smaller areas in other lobes. Heart is small and shows some sub-epieardial hemor rhages, Some hypertrophy of left ventri cle. Valves thinned. Arteries natural. All are bile stained. 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 arc natural. Many petechial hemorrhagic areas noted in the mesentery with some enlargement of mesenteric lymph nodes.
Liver is small, weight 720 gin. Capsule wrinkled. Bight lobe on section shows ureas of yellow surrounded by red arens.
Left lobe much firmer although liver cuts firmly throughout. All ducts patent. Gall 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 arc somewhat' indistinct. Kidneys show swollen coitox. IN idling of parenchyma tous degeneration of epithelial cells. Capsule strips easily. No granulation. Degenerative changes in cells of glomeruli only. No glomcrulitis. Uterus is small. Endometrium bilc-stnincd. Ovaries are natural in size; right contains corpus luteum cyst. Bladder wall is somewhat thickened. Mucosa is injected.
Microscopic examination--Li ver--From size of a through and through transverse section one suspects that the entire liver was about i 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 eolor; firm and clastic in consistency; (b) Other areas are light yellow in eolor and are scattered indiscriminately throughout reddish areas. Yellow areas vary from J to 2 in. in diameter. External surface
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 nil 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 duets are seen. These also
seem to have been spared destruction. The
yellow areas arc 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 seem to be regenerated.
Those liver cells spared destruction have
regenerated and have formed yellow islands
seen in the gross picture. There evidently
has been one or more attacks of hepatitis juilg-
ing from the different ages of the pathological
process in various parts of liver.*
Skin--Shows an increased density of
corium which stains deeply with cosin.
Some of the epidermal cells are slightly
deeper in corium than normal.
Heart--Shows mild parenchymatous
myocardial degeneration.
Kidneys--Show severe 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 ncini and of islets.
Summary--An unknown toxin has evi
dently caused a severe diffuse cytolysis in
volving most of organs, predominately the
liver. The latter has evidently undergone
and recovered from previous attacks of a
similar nature.*
Case 2--F. D.
A young man, 21 years of age, was ad mitted to the New Haven Hospital on May 2, 1931, complaining of jaundice. The his tory given was as follows:
He had worked in a wire factory coating
* Authors' italics.
December, 1933. At that 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-developed 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 nnd 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 wras soft and non-tender. The
upper edge of the liver dullness was in the
6th 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, 4,380,000; 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.
Stool--showed bile, considerable undi
gested food, small amount of fat.
Kahn lest--negative.
Liver function tests--Icteric index--30 to
50, Dromsulfonphthalein showed marked
t The waxes employed in this process are the higher chlorinated naphthalenes. These are used in a molten state in n bath through which the wire to be coated is passed. The process is partially hut not
entirely enclosed. Exhaust ventilation is in use.
3t3 JOURNAL OF INDUSTRIAL HYGIENE AND TOXICOLOGY \vol. 21, no. 2
impairment: 100% retention in 5 min., 85% retention in 30 min.
Blood chemistry: Non-protcin nitrogen, 28 mg./100 cc.; Urea N, 11 mg./lOO cc.; Serum total proteins, 0.15 mg./lOO cc,; Serum total albumin, 2.60 mg./lOO cc,; Serum total globulin, 3.49 mg./lOO cc. A/G rntio, 0.70; Flood sugar, 08.0 mg./lOO cc.; Blood calcium, 10.32 mg/100 cc,; Blood phosphorus, 4,12 mg./lOO cc.; Scrum fatty ncids, 11.3 mg./lOO cc.; Scrum lipoid phosphorus, 7.5 mg./lOO cc.; Serum total cholesterol, 10.5 mg./lOO ce.; Serum free cholesterol, 03,0 mg./IOO,
Sugar tolerance test was within normal limits.
X-ray of abdomen showed hepatic 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 10, 1934 with the diagnosis of toxic hepatitis.
lie 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 Hanks, 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 0,400 with 74% polys., and a decrease in serum albumin to 1.88%. Serum GOs con tent was 54.54. Serum chloride was 98.0 mg./IOO 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 lie died.
Anatomical diagnosis.* Extensive nec rosis, fibrosis and regeneration of liver, acute cntcro-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. II. M. Zimmerman. Grateful acknowledgement is made of his courtesy in permitting use of the records.
pneumonia (bilateral), subpleurul 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, ubdominnl 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 begun with jaundice 2 months previously with no other symptoms. This continued for about 1$ months. Two weeks before admission be became more jaundiced and concomitantly de veloped upper abdominal puin, malaise, nausea and finully vomiting--the vomitus becoming bloody in character. He was treated by his family doctor with no relief. His condition became worse and ho 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/G8. Generalized jaundice, petoehine 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
Feb. 1939] SYSTEMIC EFFECTS OF CHLORINATED HYDROCARBONS
37
all three eases, a most careful investi gation failed to reveal any other pre disposing cause for the condition. In the first ease in particular, that of a healthy young girl on her first job, the absence of any conditions predis posing to liver damage either preced ing or following her exposure to the substances in question is especially clear.
It is of interest to note that two of the cases apparently had suffered from at least one previous attack of hepati tis followed by a certain degree of improvement before the onset of the fatal attack.
In view of the fact that Drinker, Warren and Bennett found no lesions in organs other than the liver in their experimental animals, it is noteworthy that such lesions were conspicuous in all three of the cases here reported. Such lesions, are, indeed, usual find ings in cases of acute yellow atrophy of the liver in humans regardless of etiology. On the basis of present knowledge, it would be impossible to say whether they are the result of primary intoxication or are merely secondary to liver damage. In the light of the animal experiments, how ever, one would incline to the latter view and speculate as to the part played by length of exposure, in the 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 yellow atrophy of the liver when given doses of carbon tetrachloride so small as 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 this 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 eases 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 eases 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 ease 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 deaths might pos sibly have been averted.
WATER
W 11 1. A.V IJ I OA IL LibUCi V \iul. 4l, no.
. * .111 E COMMENDATIONS FOR MEDICAL persons, should not be further exposed
Control
in their work to potential liver poisons.
1. The authors wish to stress (he 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 thnt. (he 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 eases 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
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 The systemic effects resulting from
fever, malaria, gall-stones or other dis exposure to certain chlorinated naph
eases known to affect the liver ad thalenes are discussed, and the litera
versely.
ture of the subject briefly summarized.
4. Persons receiving arsphenamine Three liver deaths in workers handling
treatment for 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 susceptible mendations for prevention are given.
BIBLIOGRAPHY
1. Mayers, M. II., and Silverheiio, M. G.: Skin conditions resulting from expo sure to certain chlorinated hydro carbons. Tins J., 0, 244 (1938).
2. Lehmann, K. B.: Kurzes Lehrbuch dcr Arhcits- und Gewerbchygiene. S. Jlirzrl, Leipzig, 1010. p. 251.
3. Flinn, F. B., and Jarvis, D. E.: Action of certain chlorinated naphthalenes on the liver, l'roc. Soc. Iixper. Biol, and Med., SB, 118 (1030).
4. Drinker, C. K., Warren, M. F., and Bennett, G. A.: The problem of pos sible systemic effects from certain
chlorinated hydrocarbons. Tins J., 19, 283 (1937), 5. Courtois-Suffit: Etude sur l'intoxication profcssionnellc par le trichloronaphthalene. Ann de med. legale, 14, 422 (1934). Abstr. of paper by Touraine, A., and Mktrel, IL: Der matoses profcssionnellcs par le naphthaline et ses derivOs. Prat, med. franc., IS, 335 (1034). 6. ScuwAnTz, L.: Dermatitis from synthetic resins and waxes. Am. J. Pub. Health,
6, 586 (1936).
KITKCT OK CERTAIN LMB1 XGE.M EXT Dl'ST SAM1MJXC. IXSTRU.MEX'I'K OX THE DUST PARTICLES*
E. E. Anpkrson
( 7.i minil lCiiijiut t r, lin'jiittcrimj ,( /nit/irrlinn Diviaiun, Trni-rlrr.i 1 unitrnurc CiiMjiinn/, 1Inrtfurtl, Cmtnfclicul
THOUGH there arc many additional data on fracturing by im
A lypes of dust sampling ap pingement. paratus available, those of the
impingont type are the more coulT
Apcakatts
nionly used in this country for routine A dust chamber was designed in,
diisi surveys. The Grccnl>urg'7ftmit h which graded dusts were suspend
inipingcr has been used extensively and from which simultaneous siipfples
by flic United States HubHe Health1 2 3we4re taken by several impipfrement
Service and thus has beooinc an ac type dust sampling inslrunumts.
cepted standard for molding dust A box, 4 ft. long, 2 ftyhigh, and 2
concentrations, Greiul (]), Bloom * ft. wide, inside dimensi/ns, was built
field (2), Felincl (3)yTlurney (4), and with as smooth insidcysurfaces as con
oilier invcstigalors/navc attempted to struction would permit; all inside cor
correlate the "(punts" from other ners were covered xvitli sheet metal in
impingement type instruments with filled with wood/to give continuous
-i hose of the /ircenbiirg-Hmith ;im- smooth surfaces/(fig. 1). The inside
pinger. Except for Green (I) / the was painted with hard washable white
investigators/apparently have / not enamel, lnlyf and outlet tubes of i]
considered Mie possibility that/ Ihc inch inside /lianieter, were placed in
instruments/themselves may fn|eture each end of the box. Circulation and
I lie dust paA'lidcs and thus give
distribution of the elutriated material
'counts" Mum actually exist in t
was obtained by two small fans and by
Green lists under the meehani!
eonveGion currents produced by two
lormalio/i of smaller dust pal
I0<) w. bulbs. Two 5 in. square liand-
The ap/ilieation of shearing anil (ca Jiolcs with interchangeable covers were
ble stresses causes disinlegraliniKdof' cut in each of the long sides and the
i lie larger particles] by splitting nr to)). Each of the following was
cracking along planes of weakness in mounted on a handhole cover, a
I lie material." Kieklen and Goolden konimeter, a Banscli l.omb dust
'il were apparently the first to report counter, and Owens jet dust counter,
any definite figures on the extent of and an outlet fur the Grcenbiirg-
lliis fracturing; this paper presents Smith impinger. A rotary screen was
* Itcrcivcd fur linhlica |inn Senteililii'l' 29, located in an air lock Infill on top of I'liiS. the box through which the sized dust