Document KGgY1M92vQOrQNk2a4y3kXkJw

ERYTHRO-LEUKAEMIC MYELOSIS I N BENZENE POISONING* BY D. GALAVOTTI and F. M. TRO Ferrara B010gt1a (RECEIVED FOK PUBLICATION JANUAK'I) 37, 1950) The work I-cported in this paper was a n attempt to elucidate th'e. pathology of a case of acute leukzmia i:i a workman engaged in a n operation which ex- posed him t o a notable inhalation of benzene vapour. Chronic intoxication with benzene is classically regarded as a cause Of aplastic anamia, b u t fact that atypical cases arise referable to the same cause has made it necessary to extend the toxicological picture Of poisoning and in it other forms which ciiffcr wiclcly from the cxample gpirvcesncn. tcdPcantattiheaEndightVhigIlniatnerina(t1io9n38al) Cinongaressstufdoyr 4 leukemia, among which were forms characteri7cd by a blood-picture The Industrial Background ;,The disease occurred ;,, n,rin of p 3 ye~rrs, engaged i n works manufilcturing chcnlicill product, hcxachloro-cyclohe~ane, the ;.-isomer of - is a agriculturil! l+,x.+ ch~or series oo f~ hc yydc rl o h e x a nies ocarbons, a dcriva with the tiv following ,structure, the being active o,,c. H CL' Industrial Accidents and Occupational Disease at Frankfurt reviewed all the toxicological litcrature up to that time. and divided the blood findings which appcar in workers exposed chroni action of bcnzcnc into four groups: clinically. h i c m a t ~ l ~ g i ~ a l l ya,nd pathologically typical of aplastic a n a m i a ; (2) cases clinically rypical of anamia, but showing active h~cmopojcsis, cspccially in the bone marrow, with numerouc undifferentiated cells (pscudo-aplastic CL H The mechanism of its potent insccticidal action is not Well understood and threc hypothcscs, rlonc fully verified, have bccn put for\vi\rd. The first scs of aplastic a n z m i a e of hyperplasia Icukxmia especially in iver : and (4) cases of attribdes the action t o the similarity of thcC;tructurc of the y-isomer to that Of mcsoinositol. which is thought to interfcre with the inositol metabolism of the insects. (Inositol is hcxahydrocyclohcx;tnc.) indubiti,blc chronic or acute lCukxrnia not infre- qucntly of a Icukxmic type. Thcsc varictics of myc~opathy, of which the leuk- ,c.mia-]ikchypprplnstic pictures have &en euperimcn- The second view iS that the Compound dccornposcs in the inscct body yiclding HCI. Tlic third thcory attributes thc p O t C n t ZlCtiOn tO t h C Strong ClCCtriC moment Of its mokculc (Sladc. 1945 ; Mclnndcr. [.illy reproduced in several species of animal by 1llcanS of suitable administration o f benzene (Lignac, 19z8, 1930, 1932, 1933 ; H ~ 19~351,~lead, us to .Ittributeto [his compound not only the appearance of abnormal blood-cells characterized by regressive (hangcs, but alto a hyperplastic action on the 1946)- The manufacturing Process is carried out in large plant consisting of a closcd circuit. Bcnzcnc and chlorine are passed into vc.iscls callcd " photo- chlorinators", in which, under thc action of light. chlorine is added to the bcnzcne niolcculc with thc ~,xmopoictic orgnn5 which, in constitutionally prcdisposcd suhjcctc. may lead to the development 14'truc Icukamia. Cqa5cshave &en describkd i n thc litcrature which >resent both clinically and pathologically thc various ,swcte of ~ ~ ~ : chkroni;c ~ ~ i ly~mph, t i c ~ ~ ~ ~acukte ~; ~ ~ k,a n~d; a C~U t C~, lcuciowni~c- , -_ - - - production of' hcxachloro-cyclohexane. Thk corn- pound is then pumped a n d d r i e d it cmcrgcs from a mill-hoppcr as a rcd-brown powdcr, and ic collcctcd in suitable rcceptaclcs. I n conditionsOf work thcrc i e 11(' bility of toxic gaws emerging into thc amhicnt air : at thc point of dischargc of thc product n qpccinl local exhaust convcys thc rccidual gascc. n.r;iinly _ _lngliqh tranrlaciirn hy M.W. Goldhiat!. -- -- --__I . benzenc,which may still be present, tothccvtcrrial air. - .. . . .. .. -.B R I T I S H J O U R N A L OF I N D U S T K f A L A f E b I C I N E ~ ~ ~ s i l c h l o ~ o - ~ y c l ~ hhci1ssa nthcc propcrty ol' worhc i i t d hc t o o k to bed with fever ; ;tho brcaking up into ;i vcry fine. i.nlpaIp&k dust ~ K i b lil tcr tic WAY ;Idmi.ud JO.~UC~CV.C~. dispersei*intothe working environment with great # Clinical Features.-His Fiimily and personal history w. 5 facility, giving off a characteristic musty odour which of no significance. Objective examination showed I sticks persistently t o the workers' clothes. fair state of nutrition, a pale-pink complexion, pall;J Hazards of the Process skin, simple gingivitis, pale oro-pharynx, normal tonsil ,, a marked rater from the mouth, and slight polyadenitis T h e industrial product is impure and possesses considerable irritant effects on the mucosre and on the moist skin. probably due t o the action of hydrochloric acid still enclosed in the product or developed on contact with sweat or other liquid secretions and also to the action of chloro-benzene (mono-, di-, trt-) always present in significant concentrations of lymph glands. A slight blowing systolic murmur was found in the heart. The abdomen appeared swollen: the liver was enlarged and tender extending two fingerbreadths below the costal margin. The spleen was also enlarged and markedly tender, two and a half finget- breadths below the costal margin. Other organs showed 'no points of interest. Faint albuminuriii was noted. Wiissermann and Widal-Wright reactions were ncgativc. 10 1 5'.';11. This process presented serious health hazards during the period of experimental production and the " teething troubles" of the plant. In that period of four and a half months, the plant personnel, some 15 technicians and workers, were often subjected to the inhalation of benzene and chlorine which could not be avoided because of their unforeseeable, frequent, and easy dispersion, and in spite of all possible preventive measures and the use of appropriate respirators. \ Several employers, during that time, drew attention to symptoms of unwellness attributable to protracted exposure to benzene v a p o u r : for Blood findings were as follows : Hb. : 45;:. ... R.B.C. : 3,600,000 (2';; basophil erythroblasts ; l',',', polychroniatophils ; 3yL orthochroniic cells). W.B.C. : 34.200 (19;i neutrophils ; 2":' eosinophils : 1 % basophils ; 14?/0lymphocytes ; I "Imonocytes : 6';4 prolymphocytes ; 20/, monoblasts ; 147" mcta- myelocytes ; 20,; promyelocytes ; 3:; myeloblasts : 26:; hmiocytoblasts ; 1"', plasma cells ; Rieder cells : 8:< endothelial cells.). The temperature remained at about 100.4" but showed. slight morning remissions and reached above 102.2" in the evenings. The patient went progressively downhill. treatment being of no avail, and, on the twentieth day after entering hospital, he died. Three days before death the following data were example. gastric upsets, migrainous headache, obtained : Serum protein level, 4.60:; : MncLagan test. muscular weakness, a n d not infrequently a condition negative ; Takata-Hara test. negative ; serum bilirubin resembling alcoholic drunkenness following the accidental inhalation of high concentrations of vapour. Case Report Icvel. 4.5 mg. (direct 1.97-indirect 2.53) ; nonprotein nitrogen level, 130 mg. "6. The urine showed traces of albumin, abundant urobilin, urea (0-64'::,a)n,occnsional red cell, and fairly numerous leucocytcs in the sediment. Among these 15 employees was the worker who died Bleeding time WilS 32 minutes and coagulation time f;om acute Ieukamia. The other workers in the team have also presented signs of blood disorders pointing to a toxic action in the hxmopoictic system produced by benzene, e.g., hyperchromic anamia, leucopenia with neutropenia, and, in some cases, re lntive lymphocytosis ;iccompanied by some young cells of the granulocytic series. The worker in question was highly skilled and had been on the plant from the start, including the four-anda-half month period of plant improvement. H e remained in the dcpartmcnt after the process had been brought into normal function. Thus, during the experimental period, he was subject, as were his work mates, to frequent inhalations of benzene and chlorine nnd later, when the + -._10 minutes. The loop test, moderately positivc (+ - -) showcd deficient clot retraction. Blood examination carried out four days before death showcd : R.B.C. : 1,870,000 ([ti'':, basophil crythrobl;lsts. 2",', . in mitosis ; 34'j:, polychroniatophils ; 34''; orrhochromic cells ; 9';(l proxythroblasts). W.B.C. : 175.000 (t7";, hamocytoblrlsts. and :I smallish number of immature clcnicnts of myeloid scrics). Hb. : 32::. C.I. : 0 86. Such findings pointed to the nccd for ;i sternal puncturr which gave the following results from ;i count of SO0 cells : process had become established. he continued to work 'for about a month in an environment where benzene vapour was present although now in small quantity. He therefore had had five and a half months in greater or Jess contact with benzene vapour. He developed Aggravated symptoms : asthenia. headache, vertigo, !gingivitis, and progressive loss of weight, which he had !to a lesser degree already experienced for some time. He Lymphocytes 7 H ; c ~ I o c ~ ~ o ~ ~ ~ 6I s ~ s Granulocytes 5.5 Turk cells Monocytes 1 Endothelial cells 0.5 a 7 Lymphoblasts 0.5 Basophil crythroblasts 22 Metamyelocytcs 4.5 Polychromntophils 30 Myclocytcs 4.5 Orthochromic cclls 6 Promyclocytes 0.5 Proerythroblasts 4.5 Myeloblasts 0.5 Mitosingcrythrob1:ists 5 White series =o.33 b a s removed from his job, but his condition grew rapidly I .Red series ... . . ' it does not appear easy to escape a n retiological relation between the work in which the patient was cngaged and the blood disease which led to his death. Such a view is supported by the finding proliferative process in the bone marrow, and what constitutes its mode of action are entirely matters of opinion a n d may give rise to'many hypotheses but facts are not yet available. .. .. . .,. ... . , _.. .