Document jyooR35G8BENxv9ZD40KJOj89

R&S 028195 w Xubli,li*4 Ud*f lU Auipim al Th* IwJ < THE JOURNAL of Ihtt American Medical Association l i A 's, . \ VOL 201, NO 8, AUGUST 21, 1967 Occupational Acroosteolysis Report of 31 Cases Rex H H'ihon, Ml), William E. McCormick, MS, CarolI h\ Tatum, Ml), and John L. Creech, MD In 31 cases of acroosteolysis of the hands of workmen derma. Some have clubbing of the fingers. Only a few associated with vinyl chloride (CHsCHCI) polymerization of the cases have sought medical attention because processes, the osteolysis was specific to the distal pha of symptomatic complaints; the majority have been langes of hands and was frequently associated with Ray found through x-ray examinations of the hands. naud's symptoms. Affected personnel ranged in age from A summary of the physical findings of the ob 26 to 47. The disorder is believed to have resulted from served cases is shown in Table 1, and a detailed de a combination of physical insult, chemical Insult, and scription of the two predominantly common symp personal idiosyncrasy. The specific causes are unknown. toms follows: The prevalence was found to be less than 3% among Raynaud's Phenomenon.--This symptom com employees performing similar work. No cases were found plex has occurred in varying degrees, with one or Jn workmen using or processing the polymer or menuketuring commercial resins. both hands involved. Generally, its effect is observed as marked discomfort on exposure to cold. None of the cases have exhibited vascular changes of the feet. uring nud-1964, several complaints came to our A unilateral sympathectomy performed on one of D attention of soreness and tenderness of the the most seriously affected cases relieved mast of fingertips of workmen in a manufacturing plantthe symptoms on that side. The acroosteolysis was polymerizing vinyl chloride (CH-CHCl). Compre not altered by the sympathectomy. hensive examinations of these individuals revealed nothing of significance except a "Raynaud-like phe nomenon" of the hands, and in some cases, definite changes of the distal phalanges were apparent on roentgenograms of the hands. Since then we have observed additional cases of this unusual syndrome. It is the purpose of this manuscript to summarize our observations. Description of Syndrome Roentgenological Changes.--1The most unique characteristic of this syndrome is the unusual roent genological findings. These are described as acrooeteolysis and are illustrated in Fig 1. Itmay be present in aU of the fingers and readily observable, or only in one finger and barely discernible, as illustrated in Fig 2. X-ray films of the feet, as well as those ot the long bones and ot the skull have been made in some of these cases, with no osteolysis found other than in the distal phalanges of the hands. To date we have observed 31 cases of hand dis order among 3,000 personnel involved in vinyl Acroosteolysis is a rare clinical entity, with only 72 cases of the familial type reported up to 1965, ac chloride manufacturing and polymerization. AU cording to Cheney In his excellent review.' The have been men, between the ages of 26 and 47. We diagnosis of acroosteolysis requires expert roent have not observed any ethnic or racial tendency for the syndrome. The great majority have been char acterized by two common factors: symptoms likened genological technique and knowledge. It has been our observations that early cases of acroosteolysis will bo missed by the roentgenologist not familiar to those ascribed to Raynaud's phenomenon and acroosteolysis of the distal phalanges. A few have had no symptoms but have the roentgenographic with this condition. All of the cases on which we axe reporting have been confirmed by at least two ex perienced roentgenologists working independently. evidence of acroosteolysis. Several of the patients We established the following roentgenographic have external skin lesions on the dorsal surfaces of criteria for our diagnoses. These axe the result of Bne hands and forearms, 'with a rope-like appear our having viewed several thousand x-ray film of ance resembling chang .'s sometimes seen in sclero- the hand in our search for the cause of the syn Frcm IK* Medical OiviMOn. U F. Goodrich Co., Akron. OKml Reprint nqutalt to SOU S Main St, Akran, Ohio 44318 t Dr. Wil son). drome. 1. General: Roentgenographically,acroosteolysis, as found in workers who- are exposed to vinyl 577 83 BEST AMM-ASIrP COPY 578 chloride and polyvinyl chloride manufacturing processes, is somewhat different from that found in familial osteoporosis with acroosteolysis and in fa milial osteosclerosis with acroosteolysis. In osteopo rosis with acroosteolysis there may be compression fractures in the spine, and basilar impression of the skull, along with destruction of the midphalanges. None of these findings have been seen in these workers. The changes in the distal phalanges are similar in troth conditions. Osteosclerosis acroosteolysis observed by Andren et aP (University Hospital, Mnlma, Sweden) in twins showed diffuse sclerosis, with cortical thick ening of the shafts of the long bones and clubbing of the metaphyseal ends. The phalanges of the hands and metacarpals were foreshortened, and the distal phalanges showed acroosteolytic changes. The feet showed the same changes, except that the distal phalanges were not fragmented. There has been no evident destruction in the mid or proximal phalanges of the thumbs or fingers of these individuals and no evidence of a lytic, destruc tive lesion in the feet. We have not observed any loss of calcium salt in the bones of the wrist and remaining bones of the hand and phalanges in any of these individuals, and there has been no evident sclerosis of the wrist and hand bones. 2. Mild stage: The earliest change found in croosteolysis in these workers has been a loss of the 'cortex of one or more of the tufts of the distal pha langes, with no destruction oi the tuft or shaft of the distal phalanx. The next more advanced stage may be a small, half-moon cut in the cortex of the tuft of one or mere Table 1.--Summary of Symptoms and Findings Symptom* AcRroaoysntaauodly'ssnsywmitphtooumts, on* hand Actooileolyiii without Raynaud'* symptoms, both hand* Acrooi(ofy*(ft with Raynaud's symptoms. ona hand AcRroaoysnteaoudly'ssissywmitphtoms, both hands T.UI No. d Cues 4 $ S 17 Clubbing of fiftftrs Shin nodulOS t 1 ti 2. Mild stage of acroosteolysis with ha.'f-moon oefeet of distal phalanx of mid finger. 1. Acroosteolysis with Involvement of distal phalanges of all fingers. ,** 'i 84 JAMA. Aug 21.1967 Vo! 201, No 8 BEST AVAILABLE COPY 579 distal phalanges, or a so-called slice effect along one or more of the tufts. Figure 2 illustrates the small, khnlf-nioon cut in the cortex of the distal phalanx of 'the mid-finger. 3. Advanced stage: A more severe lytic destruc tion may be a complete loss of the tuft and a por tion of' the shaft of one or more distal phalanges as illustrated in Fig 1 in which the tuft of the distal phalanx of the right thumb and the tuft of the distal phalanx of the left fifth finger are completely absent. Additionally, there may be in the same hand a portion of the distal rim of the tuft remaining, with loss of the proximal portion of the tuft and a portion of the shaft of the phalanx, which can also be identified in the remaining phalanges in Fig 1. This loss may be of a transverse nature through the shaft and the tuft, or of an oblique type loss of bone strut-lure. 4. Healing stage: In this phase, there is often definite fragmentation of the remaining tuft and of the filled-in area where the previous destruction was noted through the shaft of the distal phalanx. This may go on to a complete bony union or remain as a fibrous union with fragmentation. In Fig 3 and 4, x-ray films of the same individual well demon strate this. This employee had almost complete reunion of the multiple fragments when first seen in November I96S and again in November 1966 (Fig 3). In the latter, the completely healed shafts and tufts of the distal phalanges are indicated by no residual fragmentation with fibrous union. There is a definite shortening of the 6haft and a widening of ----------------- ------------ ------------ ------------------ t i/ ;i d 3. Above, Aeroostcolysit with marked fragmentation of distal phalanges in Novemt v 1965. Below, Same individu al In November 1966. R&S 028197 JAMA. Aug 21, 1967 Vol 201. No 8  ^* * m j rrtny sso ACROOSTEOLVSIS--WILSON ET At the shaft and tuft, hoth in the transverse and the anteroposterior diameter. This is most likely due to a combination of constant pressure, and by the nor mal tension of the soft tissues, particularly the ten dons to the distal phalanges. Occupational Aspects of Syndrome Eased upon our observations of these 31 cases, it appears as if this syndrome may be of occupational origin and is somehow related to the process of vi nyl chloride polymerization. Its specific cause if not presently known. We are performing extensive re search in an effort to find the cause. Two other pa pers referring to the condition have appeared in the literature. The publication by Suciu et al* contains no specific information, and merely alludes to some hand problem. That of Cordier et al' presents case histories with symptoms similar to many of the cases we describe. This syndrome differs from idiopathic and familial acroostoolysis in that only the hands are involved. Vinyl Chloride Polymerization Process Polyvinyl chloride is a widely used synthetic resin. It has been manufactured commercially for more than 30 years and is used in upholstery fabric, floor and wall tile, wire insulation, phonograph records, and many other commonly used commodities. For many of these uses, the resin (CH-CHC1), is mixed taith other materials to achieve the desired physical Characteristics. The hand syndrome occurs apparent ly only in those people exposed to vinyl chloride or to other chemicals used in the manufacturing process of the resin itself or both. In addition to our exami- Teble 2.--Age Dlitributlon of Cases Acrootlwlrtli Without A** Croup fUynoucTi Symptom* 30-29 1 30-39 4- 40*49 4 AcfMitcoinH With Raynau^i Symptom* 4 12 6 nations of 3,000 personnel performing vinyl chloride* manufacturing and polymerization, we have exam ined more than 1,000-individuals who handle the finished resin or who process it into plastic prod- ducts. No cases of acroosteolysis have been found in these 1,000 persons. Basically, the manufacture of polyvinyl chloride consists of polymerizing vinyl chloride. The reac tion is accomplished in closed containers (polymerizers) with suitable catalysts and emulsifiers. Copolymers, formed by combining vinyl chloride with other monomers, create variations of the homopolymer. These are commercially produced. Following polymerization, the resin is washed, dried, -'d sold as a finely divided white powder. The polymerization operations are carried out in closed processes and provide little opportunity for employee exposure. Following the completion of the polymerization reaction, periodic cleaning of the walls and agitator of the polymerizer is necessary. The frequency of this cleaning and its method varies with the type of material used in these vessels and with diflerent manufacturers. The most common practice has been to accomplish the cleaning man ually by using hand scraping techniques, with work ers spending several hours each day on this job assignment. Personnel performing this job are com monly referred to as "polycleaners." 4. Lett, Healed icroosteolyii* with only minor roentgenographlc change*. Right, Seme Individual erne month after crushing injury to midfinger. R&S 028198 80 JAMA. Aug 21,1967 Vol 201. No 8 ACRtJoSTEOLYSIS--WILSON ET AL SSI Epidemiology We have attempted to study the relationship of job history to the occurrence of the disease. Twen ty-seven of our 31 cases have either been on the "polycleaner" job assignment at the time the syn drome appeared or have had that assignment at some time in the past. This job assignment is the only one showing any positive correlation with the occurrence of the syndrome. Attack Rofc.-The syndrome has a low attack rate. Our experience indicates it occurs only in less than'3% of all .production employees who at one time have had polycleaning experience. Age Distribution,--The youngest of our cases is 26 years old, and `he oldest is 47* with the majority falling in the 30 to 39 age group. The complete dis tribution is shown in Table 2. The appearance of the syndrome among younger employees may be influenced by the fact that the polycleaning job is one of the initial job assign ments into which employees in such plants are hired.' Incubation Period.--If this syndrome is related to occupational factors, as wc believe, then the time of exposure to these factors should be significant. We have investigated the linr.a spent on polyclean ing and, although accurate job-time assignment in formation is difficult to develop, it appears as if none of these cases has had less than 12 months poly cleaning experience. Comment To our knowledge, this is a unique and, with the exception of references 3 and 4, previously unre ported disorder. The specific cause is presently unknown, although it appears to be related to the manufacture of vinyl chloride and polyvinyl chlo ride. Not only are the x-ray findings of themselves unique, but when accompanied by the symptoms of Raynaud's phenomenon, the syndrome becomes ex tremely specific. As far as we are aware, this has not been an observed response to any toxicant in any of the animal species. We have attempted to arrive at an explanation of its cause, as well as the physio logical mechanism whereby fhc extreme specificity for the distal phalanges of the hands occurs, but have been unsuccessful. We believe the condition is the result of three factors, all of which must be present for occurrence: (1) a chemical insult, (2) a ohys'eal insult, and (3) a personal idiosyncrasy. The chemical insult could occur from one or more of the monomers, catalysts, and intermediate reaction products existing in polymerizers. A low degree of exposure to these could occur from contact with the solid, slightly moist, residue in the polymerize/ or to small quantities of vapor, absorbed either percutaneously or by inhalation. Research studies are in progress in an attempt to verify the chemical in sult factor theory. The physical insult is present in all "polyclean ers" to some degree through fhc prolonged hand scraping operations as well ns the occasional use of hammers to remove the residues. In support of the physical insult factor, we have quite recently ob served the effects of a finger injury to an existing case of this syndrome. Figure 4 (left) shows an x-ray film of the left hand of the first of these cases of acroosteolysis (accompanied by Raynaud's symp toms and skin nodules on the dorsal surfaces of the hands). The bone damage is.quite limited. Figure 4 (right) shows the same hand with the roentgeno gram taken four months after a crushing injury to the mid finger, with lysis having resulted to the tuft of* the distal phalanx. We believe this activity was stimulated by the trauma. Personal idiosyncrasy appears to be an important factor because of the low incidence of occurrence of the disorder. This is especially significant because, although all polycleaners are subjected to essential ly similar chemical and physical insults, the inci dence of this syndrome is very low, and the explana tion for this can only be made on the basis of person al idiosyncrasy. We suspect pertinent factors here are related to the individual's vascular system, the nerves controlling the blood supply to the fingers, and to the specific type of collagen in the individ ual's hands. Wc are in the process of investigating these factors. We have observed no serious disability in any of these cases. A few have been partially disabled be cause of hand soreness, to the extent that some restriction in manual activity was necessary. Im provement in the symptoms, as well as in the roent genological findings, has occurred in many cases without adequate explanation. We wish to emphasize that no cases have been found, after extensive search, in individuals either working with the finished polyvinyl chloride or its copolymers, or in processing the polymer into plastic products. In these processes, more exposure to the polymer occurs than does in the manufacturing of the polymers themselves. We presently believe that personnel assigned to polycleaning should be evaluated,- prior to assign ment, for any evidence of collagen disease, oste olysis of the hands, or abnormal response of the hands to cold insult. Any evidence of the existence* of any of these factors should contraindicate the as signment of an individual to "polycleaning,'' and thus remove, or at least minimize, the personal idk>ayncr.uy factor. References 1. Cheney, W.D.: Acro-ostcolyii*. Amer J Roentgen 54:505-617 (July) 19G5. 2. Andren, 1.. et nl: Qsteopetraaia A'-roostoolytica: Syndror-- of Osteopetrosis. Acroosteolysis end Of.cn Statuses of Shull. Aeta Chir Scand 12tif0C-a07 (Dm) 1062. 3. Stadia. I.: Drejman. I.; and ValaskaL GontrihutU Studiul Imolnavirilor Produso de Clorure do Vinil, Med Intern 1SHG7979 (Auttl 19G3. 4. Cordicr, J.M., et *1: Aeroosteolyw et I<sx*es Cttlanecx Associees Chcx Deux Ouvricre, AITsetcs au Nettoyaco D'AntoeUv**, Cnh Med Travail 4: (Jan) 1966. R&S 028199 JAMA. Aug 21.1967 o Vol 201, No 8 87 60591 CfMmfeaf Abttrtc** VoL 69. 1968 wick, N.J.). Cam, J. Pkjriol. Pharmacol. 1968, 46(4), 609-16 tsiled. Inst. Onkol., Leningrad, USSR). Farmokei. Tokxxkal. (Eng). A series of expt*. lui shown that the mechanisms by 1968, 31(3), 364-5 (Rnsa). Polyethylene polyamine (750 mg./ which the metabolism of EtOH occurs are strongly influenced by kg.) administered s.e. to rat* and mice increased the hepatic the partial pressures of the O present in the neratinr medium. monoamine oxidase and kistaminase activities, decreasing the For the most frequently used gas mist., 95% Os ^ 5% COs, ;; ranine and histamine levels in the blood and organs of tthhe^ the EtOH consumption was abnormally large, and proportional to the tonen. of L<OH in the perfusate. However, when the poisoned and rats animals. The pathol. disturbances observed with acute polyethylene polyamine poisoning in n may m system was aerated with 18% Os + 5% COi + 77% Nt, the due to the increased oxijativc dea.nination of endogenous ubW consumption of EtOH was similar to that found in the intact with the consequent formation of aldehydes, NH,, and H,0,. i The perfusate concn. of MciCO, HOAc, pyruvic acid, and BJJR 1 tic acid was measured in all expts. When EtOH was con 50S98W Effect of niacin on phagocytosis far chronic trinxtro. sumed at these two different rates, increases in the lactic :- toluene poisoning. Pidcmskii, E. L.; Chukichev, E. M.; pyruvic ratio and acetate levels of the perfusate were noted Mul'mcnko, A. M. (Perm. Univ., Perm, USSR). Farmtakot. in both types of expts. However, the utilization of g'ucose Toktikol. 1968, 31(3), 385-6 (Russ). Trinitrotoluene (TXT) by isolated perfused liver was inhibited, and acetone levels in administered orally at 30 mg./kg. daily for 6 days to rats pro creased markedly, when EtOH was consumed at abnormally rapid gressively decreased phagocytosis. Niacin administered 1 rates, although no effect was noted in the perfusate levels of these taneously at 1 mg./kg. s.c. prevented this decrease and cvea in metabolites when EtOH was consumed at normal rates. 27 creased the phagocytic activity of the leukocytes to I.5-times the references. RCYD level in control rats. BJJR 30391p Action of beryllium Iona on primary culture* of twin* 50599X Pathogenic effect of chronic exporare to vinyl chloride* cell*. Vegni Talluri, Maria; Guiggani, Vivian* (Univ. Siena, on rabbiti. Vazin, A. N.: Plokhova. E. I. (Inst. Gig. Tr. Prof- Siena,' Italy). Caryolotia 1967, 20(4), 355-67 (Eng). The zabol., Gorki, USSR). Farmakol. Toklikol. 1968, 31(3), 369- effect of Be**' poisoning on mitosis and morphology of swine 72 (Russ). In rabbits exposed to vinyl chloride (9-10 nm./l. kidney cell and lymphocyte cultures was studied. Treatment air) for 4 hrs. daily for 5.5 months altered 0-waves (fmqwacy with Be** had a harmful effect on all the mitotic phases and >80 Hz.) appeared on the electroencephalogram from the an abnormality of chromosomes was frequent. At high concns. terior hypothalamic nuclei, and the potentials of the anterior the action of Be** was less pronounced on kidney cells than on and posterior nuclei increased by 18-30 and 70-85%, rap., mu lymphocytes. Be** exerts its toxic action by competition control value*. Concomitant changes in the cardiovascular sys with Mg** either in the activation of DNA polymerase or in tem (bradycardia, arrhythmia, decreased voltage of the in the binding of DNA to histones. L. Mirone dividual electrocardiogram peaks or whole complexes, decreased 50392q Protective effect of ethyl alcohol towards *Hyl alco duration of systole, increased arterial pressure, and retarded hol-induced hepatic lesions. Schwanmann, V.; Infante, R.; blood flow) also occurred. The functional changes in the an Raisonnier, A.; Caroti, J. (CHU Saint-Aofoine, Paris, Fr.). terior and posterior hypothalamic nuclei may hvre a rAc ha the C. R. Soc. Biol. 1967, 161(12), 2425-9 (Fr). A 99-min. per pathogenesis of toxic angioneurosis due to vinyl 4ilnrM fusion of isolated rat liver with blood contg. Jlyl *k. (0.018 ml./ BJJR 180 ml.) caused a release of lactic dehydrogenase, malic dehy S0600r Brown PE. m. Administration of high doses to drogenase, and glutamic-pyruvic transaminase into the perfusate rata and mice. Graaso, P.; Gaunt, I. F.; Hall. D. .; Gotburg, end a simultaneous depletion of these enzymes from the liver; L.; Batstone, Elizabeth (Brit. Ind. Biol. Res. Assoc., Carsfeal- ale. dehydrogenase and glutamic dehydrogenase activities ton, Engl.). Food Cotmtt. Toxicol. 1968, 6(1), 1-11 (Eng). were not detected in the perfusate and were not decreased in the Acute oral toxicity studies with Brown PR gave LDh value* >2 liver. Biliary secretion was irreversibly arrested after 18-20 g./kg. and 8 g./kg. in mice and rats, rasp. The values for i-p. min. of perfusion, and hepatic lesions occurred. A 20-min. per injection were 1.5-2 g./kg. in mice and 0.75-1.15 g./kg. in rats. fusion with blood contg. EtOH prior to the treatment with aiiyl When repeated daily oral doses ranging from 0.1 to 2 g./kg. nrae ale. prevented the enzyme release, the hepatic lesi ns and the given to rats, a precipitous wt. loss and a vacuolar myopathy effect on biliary secretion, and did not eause the release or ale. of the heart ana skeletal muscles accompanied by CpufiesLui dehydrogenase or glutamic dehydrogenase activities. BPJP formation occurred with doses of 0B g./kg. and over. At the 50393c Effect of ethanol on hepatic metabolism and enzyme highest dose employed (2 g./kg.), there was also hepatic cewtri- aetMtie*. Nelson, Patricia Ann (Indiana Univ., Blooming lobular necrosis and renal tubular degeneration Pretreatment ton, Indiana). 1967, 104 pp. (Eng). Avail. Univ. Microfilms, with antibiotics reduced the incidence of muscle lwi- Re Ann Arbor, Mich., Order No. 68-7228. From Dia. Abstr. B peated i.p. injection did not have anyeffect on the heart or skch-tal 1968, 28(11), 4688. SNDC muscle. Only 2 of the 6 components of Brown FK, 2,4-diain*no- 50994a Energy-linkd calcium transport In liver mitochondria 5-(p-*ulfophenylaxo)toluene (I) and 1^-dsamino 1 (p --Tfo- daring carbon tetrachloride intoxication. Carafotl, Ernesto; pheny!aio)betiiene (II), produced musdc damage after repeated Tiozzo, Roberta (Univ. Modena, Modena, Italy). Exp. Mol. oral doses of 0.5 g./kg. Comparable doses of mixta, contg. the Paihal, 1968,9(1), 131-40 (Eng). In rats intoxicated by the gas other components as well as I or II woe considerably 1ms toxic. tric intubation of 0.5 ml. CCU/200 g., Ca'* concn. in liver mito After daily oral doses of 1 g./kg., muscle kmu were found in chondria increased ~10-fold within 18-20 hr*. However, Lp. rats, rabbits, and guinea-pigs, but none were seen in mice or injected *Ca was not taken up by hepatic mitochondria in in hamsters. The results suggest that the intestinal micofioen is toxicated rats as rapidly as in normal animals. In vitro, hepatic responsible for the breakdown of the components of Brown FK mitochoudria from CClfintoxicated rats did not show increased to toxic products. Variations between species and between ani Ca** uptake, but Ca** release induced by oxidative phosphoryla mals of the same species may be due to quaL and quant, dif tion encounters eras greatly decreased. This suggested that in ference* m the intestinal microbial-population. RCXP CCU intoxication, the balance between ADP phosphorylation 50601* Brown FR. IV. Cytopathk affect* of Brows FR and Ca** uptake is shifted fat favor of the latter, thus contribut on cardiac and skeletal muscle in the rat Grasso, P.; Mair. A.; ing to the accumulation of Ca** in mitochondria. DDJN Colberg, L.; Batstone, Elizabeth (Brit. Ind. Biol. Res. Asue,. 50695t Protective effect* of alpha-tocopherol on the hepato- Carshalton, Engl.). Food Cotmtt. Toxicol. 1968. 6(1). 13-24 tozldty of carbon tetrachloride; an electron microscope study. (Eng). Administration of 2 or 3 massive (1 g./kg.) oral dasn Meldolesi, Jacopo (Inst. Pharmacol., Univ. Milan, Milan, Italy). of Brown FK to rats induced a myopathy ji cardiac and skeletal Exp. Mol. Pathol. 1968,9(1), 141-7 (Eng). The oral administra muscles characterized by multiple vacuoles ~I-2 a in (Earn. tion of 2.5 ml./kg. CCUdild. 1:2 with liq. paraffin to rat*produced Uttrastracturolly, these consisted of ana* of fibrillolysis. af severe hepatic lesions within 24 hr*. However, liver damage was fecting initially the A-band. Histovhem., the myopathy eras markedly reduced in rats i.p. injected with the lipid antioxidant, accompanied by a moderate htenase in acid phosphatase activity 0- tocophcrol succinate (125 mg./kg.), before CCU administra and by a loss ofphosphorylaae activity- Subsequently, compictc tion. This suggested that lipid peroxidn. is the primary mecha lysis of the affected fibers ensued. In the heart, lysis was fol nism of CCU hepatotoxicity. 27 references. DDJN lowed by macrophage invasion and fibroblastic proliferation, 50S96u Distribution and toxicity of aliphatic hydrocarbons in and in skeletal muscle, by regeneration. The occurrence of body tissue*. Shugaev, B. B. (Yaroslav. Med. Inst., Yaroslavl, lipofuscin in muscle fibers am! in macrophages was scanty and USSR). Farmakol. Toklikol. 1968, 31(3), 360-3 (Ruts). Gas erratic. When Brown FK was given in the diet at a level of 'T 't. chromat' g, was used to study the distribution of 6 volatile hy fibrinolysis and an increase in the no. and electron d. of lyso- drocarbon* in the mouse and rat body tissues. The volatile somci was observed ultrasttucturally during week 2-3 of die hydrocarbon content of the brain and parenchymatous organs test. These changes were accompanied by a marked ikwtina was similar, but the level in the fatty tissue was significantly of histoebem. demonstrable acid phosphatase. Progiesaive higher than in the brain, liver, kidneys, or spleen. There was a deposition of lipofuscin was the principal pathological fcatwre parallel between the toxicity and effective cerebral concn. of iso- during week 3-12. Initial damage to the A- and 1-lunds in both prene, divinyl, and isobutylene, but not of butane, 2-melhylpcut- cardiac and skeletal muscle distinguishes the Brown FR myop 1- ene, or 2-mcthylpcnt-2-cnc. The divinyl concn. was higher in athy from that known to be produced by high doses of coeti- the medulla oblongata than in the cerebellum or cerebral cortex. custcroiils, thyroxine, cliluroquinc, or pLisnincwl, from ivhniie BJJK damage anil from muscle ilamage mulling from iltprivatiufi of S6597v Some biochemical change* in animals following acuta R, Ca, or Mg. The lysosomal changes anil accuimituiocv of polyathyiene polyamine poisoning. SoUiimskaya, E. A. (Nnuch.- lipofuscin are suggestive id primary lysosomal iLimage which