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R&S 116909 6 4 -n - lJ fMM (fAf f*p- KtY/CHs Tr?kj /,7r,K Gigiena Truda i Prof. Zabol. 1983, pp. 42-45 Makarov, I.A., Fedotova, I. V. MECHANISMS OF CARCINOGENIC ACTION OF VINYL CHLORIDE (Review of Literature) Institute of Hygiene and Occupational Diseases, Gor'ky In 1835 the German chemist Regnault synthesized a low molecular, unsatur ated, chlorinated hydrocarbon which acquired the name vinyl chloride (VC). The outstanding feature of this compound was its capacity to be polymerized which also determined its future fate as a starting material in the produc tion of many plastics. At first in the USA (1928) and then in other coun tries construction was begun on large-tonnage factories for producing polyvinyl chloride (PVC). By 1980 the total capacity of these factories in the world reached 12-12.5 million tons per year. The factors which stimu lated the increase in production of PVC were not only the significant eco nomic demands for it but also the assurance of its complete harmlessness for the human being. The rather broad use of VC as an anesthetic in surgical practice (Fao and Bertazzi) will serve as an illustration of this fact. How ever, in the middle 50's - beginning of the 60's in the USSR the first publi cations appeared concerning the toxic effect of VC on the human organism (N.A. Smirnova). In subsequent years the said articles were confirmed by R&S 116910 2 research performed by professional pathologists abroad (Suciu et al.; Wilson et al.). Prolonged intake of VC into the organism of workers leads to a systemic disorder of the connective tissue reminiscent of scleroderma (Juhe and Lange; Moulin et al . ; Brichter). The clinical picture of vinyl chloride disease (VCD) is composed of a syndrome of a disorder of the central and peripheral nervous system (V.A. Antonuyzhenko; Foa and Bertazzi; Suciu et al.) the Reino syndrome and acr o-os t eo 1 y s i s (V.A. Antonuyzhenko; N.A. Smirnova; A.V. Basalaev et al . ; Wilson et al.; Cook et al.; Dodson et al.; Juhe and Lange; Biersack et al. ; Rety et al.; Hahn et al.), the hepatolienal syndrome (Falk et al . ; Thomas et al.; Creech and Makk; Berk et al.) disorders of the skin (Juhe and Lange; Duport et al.; Veltman) fibrosis of the lung (Lange et al.; Brichter; Gordasco et al.). Experiments designed to study the mechanisms of vinyl chloride acroosteolysis revealed an unexpected property of its pathological effect, that is, a carcinogenic effect. After Maltoni published his results of an experi mental study in which he detected in many animals inocculated with the VC the manifestation of an extremely rare malignant tumor, that is to say a hemangiosarcoma of the liver, oncologically and pathologically concerted attention began to be given to this substance. In 1974 this tumor was discovered in one of some deceased workers who had been employed in a factory where PVC was produced (Creech and Johnson). After the article by Creech and Johnson a whole series of publications was printed concerning the occurrence of hemangiosarcoraa of the liver in workers involved in producing PVC and in two residents of areas adjoining the factories where this product was produced (Makk et al . ; Falk et al.; Fleig and Thiess; Conso). By the end of -1977 64 cases of death from hemangiosarcoma of the liver had been recorded, caused by .7 cv& 4 R&S 116911 3 caused by contact with VC (Spirtas and KAminski). An analysis of the experi mental and clinical material showed that VC induces the growth not only of hemangiosarcoma of the liver but also of adenocarcinoma of the stomach, and alveologenic tumor of the lungs, hepatocarcinomas, nephroblastomas, neuroblas tomas, carcinomas of the mammary glands, of various forms of connective tis sue tumors and also an increase in the quantity of systemic diseases of the blood (Maltoni; Suzuki; Brichter; Feron and Kroes; Winelt et al.; Ott et al.). A correlation of this material made it possible for Maltoni to reach the conclusion that VC is an undisputable carcinogen with a broad spectrum of effect. According to the data of experimental studies conducted by B.A* Kurlyandsky et al . , VC can be classified among the low level carcinogens (class IV of blastomogenic activity). An analysis of the general death rate of workers involved in producing PVC did not turn up any changes in its structure (Ott et al.; Fox and Collier). The only thing detected was an increase in the frequency of some forms of malignant tumors, tumors of the stomach-intestinal tract (Chearu and Nichols), of the lungs and brain (Rawls). However, attention is drawn to the fact that, for example, in the Federal Republic of Germany, with the absence of any changes in the general structure of the death rate a pronounced shortening of life was noted in workers subject to VC exposure, that is to say the hydrocarbon under study, without changing the ratio between oncologi cal and nononcological diseases it hastens their appearance and consequently it hastens the death of these workers. According to data by Thiess and Fren tzel-Beyrae, 68% of the deceased workers involved in producing PVC did not reach the age of 60. Detecting the carcinogenic effect of VC was the impetus for carrying out numerous experimental studies focused on interpreting this effect. In and of 4 itself VC is not capable of stimulating the growth of malignant tumors (Antweiler); the carcinogenic danger comes in the form of its metabolism pro ducts in the organism. The carcinogenic process under the effect of VC takes place in two stages: the first is biochemical and the second is the immune stage. It was established that the biotransformation of VC may take place in two ways. Initially under the effect of a microsomal monooxygenase (Tarkowski et al.) VC is oxidized into 2-chloroethanol, chloroacetaldehyde and monochloroacet ic acid. The said method of oxidation is observed under .3 the effect of VC on the organism at concentrations of up to 256 mg/m (Binns). At higher concentrations of the carcinogen under study, the biode struction process of VC takes place with the formation of unstable oxides and peroxides of chloroethylene (Antweiler; Binns). At the same time that the destruction process of the hydrocarbon is taking place in the organism, its "fragments1' are bonding with the thiol radicals of the tissues. Chloroacetal dehyde and chloroethylene oxide have alkylating properties and they are capable of undergoing a divalent bond with the sulfhydryl groupings of the proteins, the adeno , cytosine and guanine portions of the nucleic acids (Binns; Tarkowski et al.; Bolt et al.). The basic enzyme which supplies the conjugation of the metabolites with the thiol groupings of the protons is glutathion-S-epoxytransferase (Green and Hathway). As a result of the alkylation a whole complex of various compounds is formed which are gradually eliminated from the organism. By using gas and ion exchange chromatography in combination with mass spectrometry we were able to identify some of them, in particular, thiodiglycolic acid, N-acetalS-vinyl cysteine (Green and Hathway), N-acetal-S-( 2-oxyethyl )-cysteine, N-acetal-S-(2-chloroethyl )-cysteine , N-acetal-S-(2-hydroxyethyl)-cysteine R A C -H cn< R&S 116913 5 (Watanabe et al.), S-(2-chloroethyl)-cysteine (E.N. Dubankova and A.V. Bykhovsky), S~(2-carboxymechyl)-cysteine , thiodiacetic acid (Antweiler) and also modified nitrogen compounds of DNA - ethanodesoxyadenosine, ethanodesoxycytidine, ethanoadenine (Green and Hathway), oxyethylguanine (Laib et al.), diethylhexylphthalate (Gordasco et al.). In experiments on a culture of S. typhimurium (strains TA 98, TA 100, TA 1535 , IA 1538) the sulfhydryl metabolites of VC did not manifest a mutagenic effect (Green and Hathway). However, the metabolic "fragments" of the hydrocarbon attached to the proteins and nucleic acids confer antigenic properties on the hydrocarbon (N.F. Borisenko et al.; Binns; Bolt et al.). One result of the said process is the producing of antibodies for these proteins and nucleic acids. This mechanism forms the basis for a second (immune) stage of the carcinogenic pro cess under the effect of VC. N.F. Borisenko et al., Hicks and Sahyoun write concerning the change in immunity with chronic exposure to VC. According to data by Mizerski et al. there is a reliable increase in the concentration of IgA in the blood serum, there is an absolute and a relative increase in the number of T-lymphocytes in workers employed in the production of PVC. Ward et al. detected a poly clonal increase in the concentration in the blood of one of the classes of immunoglobulins, most frequently IgG, the presence of mixed immunoglobulins and the conversion of the Cg and C^ complement in subjects subjected to VC exposure in production conditions. In most of these subjects who came into contact with high concentrations of VC, high concentrations of antinu clear antibodies were detected. In workers subjected to exposure to low con centrations of VC the levels of immunoglobulins is practically indistinguish able from those in the control groups, no antinuclear antibodies were 't-oai.j. s s a 6 detected. All these antibodies are produced in response to proteins and nucleic acids which acquire antigen properties under the effect of VC metabo lites. As a rule, the reaction of the antigens and antibodies takes place on the membranes of the small blood vessels (Ward et al.). The detection of maximum immune shifts in subjects subjected to systema tic exposure to high concentrations of VC is apparently related to the fact that the level of VC in the organism is a dosage-dependent factor, whereas the process of separating the thiol metabolites from the urine is a constant factor (Watanabe et al.) consequently the greater the concentration of VC in the organism the longer its metabolites will be found in the tissues thus stimulating the production of antibodies. Precisely because of this the most pronounced clinical picture of VCD and the grossest changes in the immunal homeostasis are observed in subjects having significant contact with VC. Watanabe et al., using chronic inhalation to innocculate white rats with VC labeled with 14 C, established that 72 hours after cessation of the mnocculation 14 to 15% of Che VC introduced in the form of metabolites attached to proteins was still contained in the organism of the animals. This attests to the fact that the covalent bonds of the VC metabolites with Che proteins and nucleic acids are stable and long lasting. Profound changes take place in the immune system when there is a large dosage of VC introduced into the organism. In the human being the quantity of VC metabolites attached to the tissues may turn out to be incomparably higher than the indicators obtained by Watanabe et al. in experiments on rats since the rate of its metabolism in the human being is four times lower than in the rat (Brichter). Apparently the antibodies produced in response to proteins are respon sible for the development of the clinical picture of a systemic schlerosis which occurs with VCD, whereas the antinuclear antiobodies cause a r &S 116915 7 carcinogenic effect. Antibodies attached to the nucleic acids of the nucleus block the functional centers of the cell formation and conversely they create new, pathological, functional centers. The morphological equivalent of this restructuring is the chromosomal aberrations whose quantity in subjects who have come into contact with VC definitely exceeds the given indicator in the control groups (V. Georgieva and M. Tsoneva; Heath and Dumont; Fleig and Thiess; Basler and Rohrborn). The greatest number of chromosomal aberrations is observed in subjects subjected to the effect of high concentrations of VC and, as indicated above, they are the ones who have the most pronounced immune disorders. The fact that there is an increase in the oncological mor bidity only in subjects exposed to high concentrations of VC agrees well with this (V.S. Filatova et al.; Ott et al.). . Thus, both the clinical picture of a sclerodermo-like syndrome (systemic fibrosis, skin disease, Reino syndrome, acro-osteolysis) and the carcinogenic effect of VC are manifestations of one and the same thing, the immunopathological effect of a given substance. Proof of this assumption is provided in the fact of the occurrence of the experimental hemangiosarcoma only after the development of the clinical picture of a systemic toxic-immunal disorder of the vessels (Winell et al.; Maricq et al.). Subsequent proof of the pathoimmunogenesis of the tumors in VCD is supplied by analyzing the clinical pic ture for other immune diseases, large amounts of collagenoses (N.G. Guseva) for which it is characteristic to detect antinuclear antibodies frequently (S.I. Dovzhansky) and more frequently the development of tumors in comparison to the control groups (N.G. Guseva; Tuffanelli and Winkelmann; Kreysel et al.). The process of the reaction of the antibodies with the antigens of the tissues takes place basically in the cells of the connective tissue, in parti cular, membranes of the vessels. This explains why, when there is VCD, it is 8 primarily the connective tissue which suffers and sarcomas occur rather frequently, The immunobiochemica 1 schematic diagram of carcinogenesis under the effect of VC, proposed in the said survey is characteristic not only of chlor inated, saturated hydrocarbons but of many other mutagenic substances. Just like VC, all of them exert an alkylating effect (Koeman). The result of this effect is the formation of substances with antigen properties. Literature Reference AKTOHMMCeHKO B. A. BHHHJIXJIOpHaBaH 60Jl3Hb -- yraenoaopoaHUft HeftpOTOKCHKOa. ropuciift, 1980. Sauuaem A. 3. a ap.-- I'm-, rpyaa, 1972, tft 2, c. .24--27. Bopucauco H. 0. % ap. -- B' kh.: rxrseHa H tokcmtaaonui tuacntacc. Kites, 1979. c. 119-- 125. fyceea H. r. CiicreMHax cuiepoaepuHs. M., 1975. Mokxcomckuu C. H-. CxJiepoaepMBs. CapaToa, .1979. JfrodaMKoaa 3. H,, EbixoacKud A, B.--Tar. a can., 1979, M I, c. 69--74. KypjuwdcKuii B. A. h ap. -- Tam ace, 1981, 76 3, C 74--76. CMufmoaa H. A. -- B kh.: MarepHaJiu mo sonpocaM rarHCHU Tpyaa h kjihhhkm npoipeccHO- Ma.ii.Hbix fio.ieaHeii. ropbKini, 1956. c 44-- 52. CMuoMoaa H. A.-- BecTH. penTreHO.i,, 1961, V* 5. c. 63--66. 0u.icToaa B. C, n ap. -- Tnr. rpvaa. 1962 .Vt 1. 0. 26--31. Feopcueea B., Uoneea M. -- CtBp. mcz. (Co(piisl. 1979, t. 30. c. 651--655. Anriceiler H. -- Environm. Hlth Perspect., 1976, v. 17. p. 217--219. Basler A.. Rohrborn G. -- Arch. Toxikol., 1980, Bd 45, S. 1--7. Berk P, D. et a] --Ann. intern. Med.. 1976, v. 84. p. 717--731. Biersack H.. J. et ai. -- Acta hepato-gastroent., 1977. Bd 24. S. 357--361. Binss C. HB. -- J. Soc. Occup. Med., 1979, v. 29, p. 134--141. Bolt H. M. et al. --J. Arch. Toxikol., 1980, N 3, Suppl., p. 129--142. Brichter A. -- Forschungsberichte des Landes Nordrehein-Westfalen. Berlin, 1979, N 2813, S. 126. Chearu L.. Nichols W. S. -- J. occup. Med, 1977, v. 19. p. 623--628. Conso F. -- Med, Chir. Dig., 1979, v. 8, p. 431-- 433. R&S 116916 R&S 116917 9 Cook IT. A. et al. -- Arch. Environm. Hlth 1971, v. 22, p. 74--82. Creech J. L,, Johnson M. N. -- J. occtip. Mad 1974, v. 16. p. 150--151. Creech J. L., Makk J. L -- Ann. N, Y. Acad. Sd, 1975. V. 246, p. 88--94. Dodson V. N. -- Arch. Environm. Hlth, 1971, v. 22. p. 83--91. Duport J. et ah--Arch. MaL prof, 1975, v.36, p. 225--241. Falk H. et at -- JJLM.A., 1974, v. 230, p. 59-- Feron V. J., Kroes R. -- Toxicology. 1979, v. 13. p. 131--141. Fleig 7, Thiess A. M. -- J. occup. Med., 1978, v. 20, p. 557--561. Foa 1'.. Bertaxxi P. A. -- Med. d. Lavoro, 1974, v. 65, p, 401--420. Fox A. J.. CollUr P. . -- Brit J. industr. Med, 1977, v. 34, p. 1--10. Cordasco E. M. et al. -- Chest 1980, v. 78, p. 828--834. Green T., Hatktoay D. E. -- Chem. BioL Inte ract, 1977, v. 17, p. 137--150. Hahn E. et al,-- Isral. J. med. Sd, 1979, v. 15, p. 218--222. Heath C. IP, 'Dumont C. R. -- Environm. Rea. 1977, v. 14. p. 68--72. Hicks C. IT., Sahuoun H. A.-- Brit J. Pharma col, 1981, v. 72, p. 553--554. Juhe S, Lange C. Dtsch. med. Wschr, 1972, Bd 97, S. 1922--1923. Koeman G. H. -- Tfjdschr. watervoor2. a anf- v2a02lw. ater behandel, 1981, v. 14, pi 200-- Kreusel H. et al. -- Hautarzt, 1976, Bd 27. S. 226--233. Laid R. J. et al. -- J. Cancer. Res, 1981, v.99. p. 33--34. Lange C. E. et al. -- Int Arch. Arbeitsmed, 1973, Bd 32, S. 1--32. Makk L. et at -- J.A.M.A., 1974, v. 230, p. 64-- Maltoni C. Experiments of Vinyl Chloride. Washington, 1974. Maricq H. R. et at -- J-A.M.A., 1976, v 236 p. 1368--1371. \hzers`.-. J. e; at -- Przegl. let., 1979. v. 36. p. 665--668. Moulin G ei at --Ann. Derm. Svph. (Paris). 1974. v. 101, p. 33--34. On Al. G. e: at -- Arch, environm. Hlth, 1975 v. 30. p. 333--339. Ratals R. -- Chem. Eng. News, 1980, v 58. p. 27--28. Regnaul: V. -- Justus Liebig's Ann. Chem, 1835, v. 14. p. 22--38. Reiy J. e; at -- Arch. Mat prof, 1974. r 5 p. 733--738. ' Spirtes R,, Kaminski R. -- J. occup. Med, 1978, v. 20. p. 427--423. Sudu J. et aL --Med. int (Milano). 1963. v. 15, p. 967--978. Suzuki Y. -- Environm. Res, 1978, v. 16. p. 285--301. Tarkoaski S. et at-- >K. nir. aniueyiio.", (Hpa- ra). 1980. \. 24. p. 228--235. Thiess A, At., Frentzci-Beyme R. -- J. occup. Med, 1975. v. 17, p, 430--432. Thomas L. B. et at--New Engl. J. Med.. 1975. v. 292. p. 17--22. Tuffanelli D, Winkelmann R, -- Arch. Derm, 1961, v. 84. p. 359-371. I'eft man G. -- Thcrapiewochc, 1960, Bd 30. S. 5354--5358. tTard Al. A. et at--Brit. med. J.. 1976, v. 1, p. 936--938. Walanabe P. G. et at-- Toxicol, appl. Pharma col, 1976, v. 37, p. 49--50. Wilson R. H. et ah --J.A.M.A, 1967, v. 201, p. 577--581. Winell M et at--Environm. Hlth Perspect, 1976, v. 17, p. 211--216. COJIEPKAHHE . CONTENTS H3MEPOB H. d>. 60 aer Haywo-Hcc.ne.aoBarcAbCKoxy HHcnnyry ranieHH Tpyaa h opo0ecCHOBaAbHUJc 3a6oaesaBH& AMH CCCP 1 IZMEROV, N, F. The 60th anniversary of the Research Institute of Labor Hygiene* and Occupational Diseases of the Academy of Medical Sciences of the USSR JISDt r. H. OHsuonoreveame MezaHHSMbi ajunrauMH cepaewo-cocyaHCToS h TepuoperyajmHOHBoil chctcm qph bomchctbhh hs MeraJuyproB bucokoA TeuneparypH Bosayxa 5 LYAKH, G. D. Physiologic mechanisms of adaptation of the cardiovascular and ther moregulatory systems in exposure of metalmakers to high ambient temperature PATHEP E. M_, flEMHHA ZL-*L, EBJIAMnHEBA M. a, IUKOJIbHHKOB E R. KHPHHHHHKOB A. 3, KAXOHH E. T- CTPEJISEBA H. E. K sonpoey o Hopuspobshkh mncpoiauiaxa juu Jan yxcracHHoro Tpyaa (aa rrpm>epe -xaGmu Manusacra uarHcrpaJMoro jjokomotub*) --- 10 RATHER, E, M., DEMINA, D. M., EVLAM- PIEVA M. N, SHKOLNIKOV. B. I., KIR. PICHNIKOV. A. B., KAKHOYAN, E. G, STRELYAEVA N. E. Standardization of the microclimate for workers engaged in intelle ctual work (as examplified by the driver's cab of a main-line locomotive)' BOPOBbEB A.. A. -0co6eBHOOT AiairraiXHH aiopasoa k npoHaBOAcneamoi ycaoanHM npU HopHBpoaaHHH' MaKposjanara ^kbxux nowemesaa cyaoa IS VOROBIEV, A A Features of adaptation of sailors to wormng conditions in standar- , dization of the microclimate in the living compartments of ships CKOPOXOE B. M. Oonoaoro*r8rBeHHqe- cxoe ofiocaoBaiuie -onraMiaanBH Tpyaa ups peMOHTe cospeMesHux xapKBOBamx nmeft Ooawnoro oOMua 19 SKOROKHOD, V. M. Physiologic and hygi enic bases ior optimization of labor during maintenance of present-day large open-he arth furnaces AJIHEBA P. X XHTBeancooui omasa ary- Ma H BB6paSMB B HdpTBBOH npOMUUJMHHO- CS8 . *, 21 . ALIEVA R. Kh. Hygienic assessment of noi se and vibration in oil industry MOHAEHKOBA A. M, PbDKKOBA M. H. 24 MONAENKOVA A M, RYZHKOVA M. N. r%* Hexoropwe htoth.-h nepmegrrow mayanix HccaesoBaiuifi b co>peMeno& KaHHBKe HDO- Some results and prospects of research into the clinical picture of occupational diseases <peccHoaaabHOH jiatoaonoi ' 3 AH3HHA JL' JL,BOJIKOBA.JL TL-Coctob- 28 AIZ1NA*N.-L, VOLKOVA A P. Humoral _ -nut Tynopaasworo -Mitymti* mpa urpodmc- immunity un occupational, chronic pulmonary- cnoaaaunix jcpoBmeamx anau *sa6oae-. diseases - -. tnin V, - APOHOBA F.. B.-*0 dSpoTBBOcwnnKnaeecKOM -31 ARONOVA G- V. Antisilicotic and side ef " -m nobamoM ju&cnwi oioMrontpenapan /nn- fect of the new drug pyracryl_ .paKPHJD- . .. KAPMOJIHH A--2L, JiynEHKO Jl. A. ~35 KARMOUN. JL LUTSENKO, L. A Dif- -O ^n<p4wpeMnHpoBamoii -yvere caacnepCHoro jerentiBted ^registration of the coal aerosol .. cocraaa aspoaoJi* .yTrw npg xmeHae^asaeAcr- dispersed composition in assessment of the Bwmuaa-aa pa6onxunax effect of dust-on the workers rWyPABBEBA ~-CFR-Go*epcitJicioaHBe we- - -39 ' MURAVIEVA S. I. Improvement of the me TOSOH -KOHTpaas -npesHHx BemeciB - B .sosay- thods for monitoring the -content of iarmful_ xe .pafoveh soxn"v" j J_y* -'ysiibstancesanttheiair of worksites - - - MAKAPOB R A^-*OE20T0BA3L.B. K bo-^ i 42 MAKAROV.X.A, FEDOTOVA I. V. Mecha- ' ..mpocy -o MexaEHSwax xaHueporesBoro jeSer- nisms oi carcinogenic action- of vinyichloride -ww BBBHjmopiijta *(06sop jtttrepaTypu) . (re\iew of literature) --.^y . 1 - tft-CTA' -J^Kpanne coofiueMii i*' '' -Brief Communications rheakoba c. x. annrrEHH b e, 45 RYBAKOVA '-S. A, EPSTEIN. B. B, AIDI- JfflPHHOB J. B.. BPAUHXHH B. 3., py. NOV. G. V^ BRATSIKHIN, B. D, RUBA- "BABOBvZ^H-~HcnoJiBSoaHBe nntojca nepeso- NOV, G. P. Advanced training in improve aorojanacaapafioiM juin ycwsesa ? pocy, CTBeHHOBpacaHHxapHoro .aassopa ...,i ycao; ment of the State sanitary inspection of the working conditions of miners MB Tpyj KHPHJCTOBJB^^^OPOSOBA x nOTlDUlHA^jj^gtgM^^O ~P- H.-Obmt 46 KIRILLOV, V. A MOROZOVA T. K, -PO-: TEKHINA "V- A, SAMUILO, O. I. Experi 00 ence of using'group hygienic characteristics, -in the pubiic health system-in Novokuznetsk. apje*-3 3* -- USHKOVA J. N, DVORKIN, E. A. Appro aches to ^standardization of the maximum - Mypaebtea C. H., Eopucoe H. E., Eopucoea Jl. H. h xp--- Tau *e, 1981, N? 2, c. 51. MerojtmecKHe yxaaaHHa Ha ueroxu onpexexeHBR BpeXBUX HemeCTB B BOAXyie. M, 1979, bus, 15. Canotfxuu Ji. B., yMtHoea H. 71,-- Tbt. Tpyaa, 1980, 8. c. 5--8. TeZHmecHBe ytnoBHs sa mctoxh onpeAexeHHa BpeAHux seuecTB b BOMyxe. M., 1973. sun. 9. Kimmerle ],. Eben A -- 1st Arch. Arbeitsmed., 1975, Bd 34, S. 127--136. nocTynJLU 17.D2.8i IMPROVEMENT OF THE METHODS FOR MONITORING THE CONTENT OF HARMFUL. SUBSTANCES IN THE AIR OF WORKSITES. S. /. Muravieva For optimization of the control over the content oi harmful substances in the air of worksites effective methods for sample collec tion and highly sensitive methods oi analysis should be used.' New- efficacious absorption ma terials (AOAC-V filters for collection of samples) are described, as well as rapid sensi tive chromatographic procedures lor assaying a number of chemical compounds and their mix tures. Development of methods for control over the environment is an important trend in oc cupational hygiene. TOK lB-eOL-efeS1143KS47.4IUaM<0a4) - r ~ ~ =' H. A. MAKAPOB, TL 3. d>EB0T0BA 1 ~ .. K Bonpocy O MEXAHH3MAX KAHUEPOTEMHOFO jaEBCTBHR BHHHJIXJIOPHJIA (0E30PJIHTEPATyPbl) HnuTirn'T THmeHU Tpyxa H mpo<psa6ojieaaHHH, r. fopwcHH - 3 1835 r. Beuetuaft xbmksRegnault cmrre- Bnpoaan MB3xoMoneKyaBpua63eapeaeithsuii xxo- pHpoaaHEuA ynaeBoiopotA, noayvmnad Hasaajore joaopHcroro bshhm unt Bmoumaopma (BX). OcofieaHocmo srora coemBesu buxa caoeoteocn> noJUMepasHpoBancft, tto b onpejteaBao -ero Aajmeftmyio cyxsby--sax-acxoxHoro upoxyxrz b spoHBBOAcrBe -msotbx- naacnree- ocbx mscc. Caavaxa b CIIIA (1928),.s aaTeM h jpyng crpaaax BassBaerca ctpobtcabctbo mboJxnoasaxBux sbbobob :no spoaBBoseny mum-BHBUnaopBjta (IIBX). K i960 r. - cysnapHaji Momaocm stex sbbobob m -mbpe Jtocraraaa 12--12,5 mis. tohh b tou. -OaxTopaMB. CTRMVjapyrmHMB yBemmsae rrpoHSBoxers HBX burn Be toxbko aBanreJOBue -axOHOMHsecxse JiotpefiBoenr b fleu.cso b yepeH*ocTi> b.-umhoh KSesspesBoern ero jum -eeaUBexa- l&unocipanBed BToro ciryXHT <pa*r bobobho snpoHoro xenonssobbhbh 3X b xaxecree aaeeroirpyiomero se.xneena - b AHpypiaseacOH npaxixKe (Foa h 'Bertam). OxBaxo b cepeirae 50-x --- Haiaxe 60-x rtuos b CCCP bum osybXHXOBaHH nepsue coobmeBBB.oTDKCBBecxoM juAcnnuTiX aa opra-bbbm senoBexa (H. A Cubpbobb). B nocaexyjomwe roan xaBHue cooOmesiw dunHUOUTBepauie- -BujiconeBOBaBBSMR sapyOexHHx npo^marosoroB (Sudn b cobbt.; .Wilson h coibt.). JUneauoe nocryimeHBe BX b opraHMM pabom npHBOBBT k atentaouy nopaxceHino coeBBBBTeJDBoP TKiHB, HanoMHHaiomewy cKjre- poBepMHio (Juhe b Lange; Moulin h cobbt: Briditer). Jtonstmecxafl xapTBBa BHBBBxnopiuhom OoaesHB (BX5) cxaBsuMerear m cmupoMa nopaateHRB nesTpaABOft b nepetpepintecKOH BepaaoB cbckku (B. A AsTOBKixeHKO; Foa h Beriazxi; Eudu h coibt.), caaspoua Pernio axpooirreoBBaa (B. A Ahtohjowchko; H. 'A CMHpBoaa; A B. Eacasaes coaaT.; Wflson a coaBT.; Cook v coaBT.; Dodson h coasT^ Jobe h Lange; Biereack h coarr.; Rety b cobbt.; Hahn s coaBT.), TenaTtutHCBaJu>Horo cuBJtpoMa (Falk n coaBT.; Thomas n coaBT.; Creech h Makk; Berk cobbt.), nopaaceiiBB hobcb (Juhe- b Lange; Duport b cobbt.; Veit- man), <|>Rbpo3a aentHx (Lange a coaBT.; Brichter, Gordaaco b cobbt.). BiccneptiMeBTU no HsyweRRio mczbbbbmob bb- KBBXBOpBBHOro aKpOOCTe&JlHBa BUBBUtR HeO/KHBBBRyio ocobeHHoern. ero nsToaonraecKoro Befictbhs -- KaHUeporeHHbifi BtpiheKT. Ocobo npn- CTBAaoe BBBMBBae x sToMy BemecTBy npodma- Toaors r obxobotr ctsjir npoxBBim nocae onybaxxoaaHBR pesyJbTaTOB SKCnepaueBraBbhoto BCcaeflOBBBMB Maltoni, - obeapyiSHBUiero noBsaeBRe y ofBOTHX sarpaBJiexHur BX bchbot- bux xpafise pexxoft 3Jioxaveerschbob onyxoJiB-- reMBBniocapxoMM newiB. B 1974 r. sra onyxoax buna Bi&BeBa y oxHoro rs yuepniHX pabosax 3BBoxa . no npoBssoscTBy I7BX (Creech r Johnson). IJook craTtH Creech h Johnson b nexbth noRBuaca nenax cepx nyftffHxanxfi o BOSBBxaoBesBR rexaBTRocapKOMu -oexeBB y paboxBX npoHiBoxcrsa IIBX h 2 aantiei paAohob, opBaeraannix x aaBoaaM, rBe-npoasBOABTca Brer npoayrr .TMakk h cobbt.; Falk n cobbt.; Fleig b Thiess; Conso). K xoHiiy 1977 r. buao aaperHCrpapoBBBO 64 cxyRax CMepn-or reuaftTROCapKOMU neveHH, ObyCJIOBJieBTHOH KOKTaKTOM c BX (Spirtas RiCiiminski). ABartB3 sxcnepRMffi: -TBBbBoro r KiiHHHiecxoio uaTepBaaa noKasfciaaer, xto BX HHsyURpyeT pocr Be tojibko re- MasrBOcapKOMu jneveHH, ho h axeecixapSHHOMU xejiyaxa, aBuetuioreHRoft onyxoaR nerxBX, reneToxapoBROMu, HeifipobaaeroMU, BeApobaacroMU, XapnBROMU MOJlORRUX Btexes, paaRRIRUX tpopM coesBRRTejisHOTxaHHUX onyxonei, a tbkxte -yBeJiRveHiie RoawReciBa aicreMBUX saboae- BaHHH xposR (Maltoni; Suzuki; Brichter; Feron a Kroes; Winell a coaBT.; Ott h cobbt.). Obob- ineHne sroro uarepHaJia uosboxbxo Maltoni cxexarb buboa, VTO BX -- besycaoBHuA xaime- poreH niRpoxoro cnexTpa xeAcraHX. Ho xshhum BxcnepBMeHTaxhHUx HccxexoBaHHfi E. A KypxxBxexoro h coaBT., BX MoxteT 6un> OTHecew k MXnoaKTRBHHM KaRoeporeRau . (IV xxacc bxacTOMorexHOH bxtrbrocth). Anajim obmeA CMepTRoerR paboxsx npomBoxcraa ITBX He - bubbex RSMOieHBA -ee crpyxTypu (Ott h coairr.; Fox h Collier). ObHapyxH- 42 i 1 saxocb Toau <popM 3-ioxa1. 33 HO-KHUiexHorc 50 tax H M03I7 IP -ebs BHHwai >pr npH or rptf CMepTH >MeHHe acHa ^ HCTBHK) BX leHHB coo<P leoHxaxon noxBJieHHt whx, no * yMepmi xocraraxH sc ObHapyrae XBJWOCb TOX1 hux axcnepH saeKHux Ha no cebe.BX mipOBBTS p (Antweiler); eraMBiot npi RH3Me. npou BX nporexae exas, J-a -- ycraaoBXe xer nporexa nox xeacTBHi au (Tarkows HRe BX ao m MOHOxaopy oxHcaeuBB cn BX b KoaaeHboaee aucoxr neporeHa npo c obpaaoaaBH CB XhOpBTHJU . MeBHo c .npo b opraBBaue BOMKOB> C Xaopanemw J Baer bbkbjir; BCTynars a x 1 hums rpynn .shtoshbobum; robux kHcno 1 Bolt H COBBT RHBaxmiHM K bumr rpynnr THOH-S-Snoxci B pesya&T jiuA xounxeK noereneHBo b " trerasOBOH R MO *'J bRHaHHB C M . . empBURpOEETl ' "THOAItrJIHKOXe - -RicTeRH (Grt OKCR9TSfl)-rni! TwereBR, N(Watanabe a 4 ' (3. H. E6a XapbOKCBMeTE jiotv (Antwe asoTRcrae co 3eB03HH, -5T: (Green b --H; COBBT.), jm coaBT.). B onurax - (urraMMU TA cyxktprHapKAi MyrareHHoro. R&S 116920 ,Trf* j BaaOCh TOJlbKO yBejIHTOHHe HaCTOThl BtKOTOpbiX (popn 3.ioKaqecTBenHbix onyxoaed -- xeayAOH* Ho-KKUieqHoro TpaKTa (Chearo h Nichols), aerkhx h Mcura (Rawls). Oaxaxo oGpamaeT Ha ceGx BHHiiaHBe tot (paxr, hto, Hanpxxep, b OPT npa OTcyTCTBHH raxeHeHHd oGmed cTpyxTypu cMapTHOCTH OTMeqaeTCH BUpajtceHfloe yxo- poneHxe 3KH3HH paGoHxx, noABepraioiiuixcH bos- AeficTBHio BX t. e. uayqaexuH yraeBOAOpaa, He H3MeHHH cooTHoojeHHJi xejKAy OHKCMiormecKHMH a HeoHKonorHqecKHMH aaGoaeBaxHXXK, ycxopaer hi noxaaexHe, a caeAOBaTeabHO, h cxeprb sthx paGoHxx. no AauHux Thiess h Frentxel-Beyme, 68 % yxepmHx paGoHHX npoaaBOACTBa IIBX He AOCTHrajiB Boapacra 60 Jier. 06HapyxeHHe KaxueporeHHoro AedcTBHX BX BBHAocb toxhkom x npoBeaenmo XHonmcneahbix aKcnepHxeirraJibHHx HccaeAOBBHHd, HanpaBJieHHBlX Ha pacmH(|)pOBKy BTOrO.AedcTBHX. Cax do ceGe.BX He oGaaAaer cxocoGhoctmo cthmvjmpoBaTb pocT saoKaqecTBeHHUx onyxoaed (Antweiler); xameporeHHyio onacHOCTb npea- cthbahiot npoAyKTU xeraGoAHaxa ero b opraHHBue. ripouecc KaHneporeseBa boa AedcTBHeii BX npoTexaer b 2 ct3Ahh: 1-h -- Ghoxhmhto* cxax, 2-a -- HMMyuxaH. y-craHOBJieHO, hto GHOTpaHapopManax BX moxrr npoTexarb Ayxx nyrxxH. ilepBoxanaabHO hoa jeHCTBHeu MHxpocoxaabHod MOHOOKCHrena3U (Tarkowski h cobbt.) hpohcxoaht oxxcaehhc BX ao 2-xAopsTaaoJia, xaopaneraabAerHAa h xoHoxaopyxcycKod khcjiotu. XLaHHhiA nyn> OEHcaeHHH OTMeaea np abhctshh rb opraHHSM BX b KOHneBTpaitBBX ao 256 mt/mj (Binns). npa Goaee bhcokhx KOHHeHTpanaax H3VHaeworo xaH- neporexa nponecc GHOAeerpyxnitH BX npGrexaeT c ofipaaoBaHHeM HeycroftHHBiix okhch h nepexxch xaopBTRAeHa (Antweiler; Binns). OaHOBpe- xchho c nponeccox paapyrnessH yraeBoaopona b opraHBBxe npoTeKaer nponecc csnaH ero <o6* AOXKOBi C THOAOBblXH paaWKBaaMH Txaxed. XxopanerashAerHA h okrcb xaopBnureHa oGaaaaeT ajiKHjJHpyioniHMH cbohctb3Mh a cnocoGHU Bcrynatb b KOBaaeHTHne cbbbr c cyawprHApHAbRuiiH rpynnHpoBKaxH GeaxoB, aneHHHOBHMH, 0RT03HH0BHMH H ryBHHBOBXXH HaCTHXH HyXJieHhobux rhcaot (Binns; Tarkowski h coasr.; Bolt h coaBT.). Ochobhhx (jiepMeHTOM, oGecnemnmwiiwnn KOHWOranBIO MeTaGOASTOB C THOAO- bhxb rpytmHpoBKauH GeaxoB, HBaxercx rayraTHOH-S-anoKCHATpaHctpepaaa (Green h Hathway). B pesyaiiTaTe aaxHaxpoBBHHX oGpasyercx ue- awh xoxnaexc paaaxHHHx coeAHxexxfi, xoTopue nocreneHHo buboahtcx hs opransaxa. MeroflaxH rasoBOM h HOHooGxeHHoft xpoxaTorpa0H s kox- GnBanHH c xacc-cneKTpoxcfrpHed yaaaocb hach- THtpBHHpOBaTb HeKOTOpbie K3 HEX, B RaCTHOCTH THOAHraHKoaeByro ttHcaory, N-anermi-S-BHHHA- nHcreBH (Green h Hathway), N-anerHa-S-(2- oKcH9THa)-HHcTeHH, N-anemn-S-(2-xaop3THa) - HHCTeHH, N*aaeTHa-S*(2-rHApoKcnTHa)-nHCTeHH (Watanabe h coaBT.), S-(2-xaopaTHa)-uhctchh (3. H. HioGaHKOBa h A. B. Buxobckhh), S-(2- KapOoKCHMerna)-HHcreHH, THOAHyKcycuyio khc- aorry (Antweiler), a Taiuxe xoAH()>HUHpoBaHHue a30THCTHe coeAHHeHHH J(HK -- 3TaH0Ae30KCHa- ACH03HH, STaHOAeBOKCHHHTHAHR, STaHOaaeHHH (Green h Hathway), oKcasmnryaHHH (Laib'H cosbt.), AR9THareKCHa<trraaaT (Gordasco h C03BT.). B onxxax Ha KyabType S. typhimurium (mraxxu IA 98, TA 100, TA 1535, TA 1538) cyab<t>rHApHAbHbie MeTaGoanTx BX ne rpohbhah xyrareHHoro acActbhh (Green h Hathway). 0ah3K0 (pHKcapoBaHHue aa Geaicax a RymieH- hobbix KHcaorax xeTaGoaHHecKBe <oGaoxKH yraeBOAOpOAa npuAaiOT nocaeAHHx aHTHreHHue cBoucTBa (H. 4>. BopKceHKO h coaBT.; Binns; Bolt h coaBT.). PesyabTaTOM ASHHoro npoaecca HBAaeTCH BupaGoTKa aHTHTea k sthx Geateax h HyKaeHHOBMM KHcaoTaM. 3tot MexanusM aokkt B OCHOBe BTOpOd (HMMyHHOfi) ctbahh xaHuepo- reHHoro npouecca boa B03AedcTBHeM BX. OG H3xeHeHHH axxyHHTeTa npH xpoftHaecKox bo3Amctbhh BX HHinyT R O. BopnceHKO h coabt., Hicks h Sahyoun. Flo ashhum Mizerski h coaBT., y paGoHHX, saHjrrbix b npoH3BOACTBe nBX HaGaioAaiOTCH AOCTOBepuoe noBbimeHHe KOHneHTpaitHH IgA B CblBOpcmte KpOBH, OTHOCHreabHWH h aGcoaioTHbid pocr HHcaa T-ahk^jontrroB. Ward h cosbt. oGBapyacBAH y ahu, noa- BeprajoiHHxca soaAeHCTBHio BX s ycaoBHux npOK3BOACTBa, aoAHxaoHaabHoe yBenaqeHHe kohUeflTpaHHH B KpOBH OAHOro H3 KJiaCCOB HXxyHoraoGyaHHOB, name Bcero IgG, HaaHHHe cxemaHHbix HXxyHoraoGyaHHOB h KOHBepCHio KoxnaexeHTa C h C+. y GoabrnKHcraa aim, KOHTaKTHpymmHX C BXCOKHXH KOHUeHTpaOHRXH BX oGHapyxeRU aucoiuie THTpw aHTHasepHxx aHTHTea. V paGoiax, noABepraioHutxcH BOSAed- CTBHJO XaAUX KOHHeRTpaOHd BX ypoBHR HMxy- BoraoGyARBOB npaKTHtecxH He oTAHHaioTCH ot TSKOBblX B KOBTpOAbHblX rpyHHaX, aHTHHACpHbie aHTHTeaa He oGHapyXHBaioTCH. Bee bth 2hth- Teaa BUpaGaTUBatorca k Geaxax h HyxaeHno- BHX KHCAOTBX, HpHOGperaiOUIHX BOA BAHHHHeX xeTaGoaHTOB BX aHTHreHHue CBOdcTsa. Kax npaBHao, peaxsHH BaaHXOAedcTBHH aHTHreHOB h aHTHTea npoHCxOAHT Ha xexOpaHax xeaxHX xposeHocHux cocyAOB (Ward h cobbt,). OGHapyxeme xaxcHxaabHbtx HxxyHHUx cabhtob y ahk, noABepranniHxcx CHcrexaTHteexoxy BOSAedCTBHIO BUCOKHX XOHHeHTpaaHd BX no-BHAHxouy, cBH3ano c Tex, hto ypoBeHb BX b opraHHSxe XBaaeTCH a03038bhchmoh aeaHHHHOd, Toraa xax nponecc BiueaeHHH THoaoBUX xeTaGoaHTOB C XOHOd -- BeaHHHHB nOCTOHH- Haa (Watanabe h coaBT.), caenoBBTeabHO, Hex Goabmee xoaHHecTBO BX nocrynaer b opraHH3X, Tex AOAbme ero xeraGoaHTU Gyayr HaxoAHTbca b Txasax, cTHxyaHpya BxpaGorxy aHTHTea. HxeHHO nosToxy HanGoaee BupaaceHhbh KAHHHHecxaH xapTHHa BXB h HaHGoaee rpyGue H3xeHeHBH HxxyHHoro roxeocTaaa hbGaioABtOTCH y ann, HxeioniHx sHatHreabHud xosTaXT c BX Watanabe h coaBT., npHxesHBUiHe xpoHHiecxHe HHraaHHHOHHhie saTpaBKH Geaaix xpuc BX xeqeHHoro 14C, ycTaHOBHAH, rro eepes 72 *? nocae npeKpameHHH aaTpaBKH b opraHHsxe hehBOTHHX COAepSCHTCH 14--15 % OT BBeaeHHOrO BX b BHAe (pHKCHpoBaBHiax c GeaxaxH MeTaGoahtob. 3to cBHAereabCTByct o tox, hto KOBaaeHTHtie cbhsh MeTaGoaHTOB BX c GeaxaxH h HyxaeHHOBXMH KHcaoraxH npoiHbi h npoAoaacxTeabHbt. npH Goabmoft aoae nocTynHBmero b opraHH3M BX npoHcxoAHT rayGoxHe H3xeHeHHH b HxxyHHod cHCTeMe. Y HeaoBexa xoaHnecTBO 4>HKCHpOBaHHbtX B TKaHHX XeTafiOAHTOB BX MO* ateT OKaaaTbca HecpaBHeHHO Buuie noxa3aTeaed, noavHeHHux Watanabe h coaBT. b onuTax Ha Kpucax, rax xax exopoefb MeraSoan3Ma ero y HeaoBexa b 4 pasa Hnace, tom y xpucu (Brichter). BupaGaTbiaaeMue K GeaxaM aHTHTeaa, no-BH* AHMOMy, OTBercTBeHHx 3a pasBHTHe xaHHHHecKod xapTHHU cHcrexHoro cxaepo3a, BoaHHxaiomero npH BXB, TorAa xax axTxxnepHwe aHTHTear oGycaoBAKsaioT xaHueporexHud adxpexT. Ahtm- Teaa,. (pHKCHpyx>niHecx Ha HyuiexHOBUx xxcao* 43 Tax JUpa, fijioKnpyiOT (pyHKiUiOHaabtiue ueHTpw xjieToiuoro o6pa30BaHua h, nao6opor, ccaaaioT noBue, naTcuiontiecxHe, <pyHKHH0Ha3bHiiie ueHT- pu. Mop(pc.iorH<iecxHM sKBHaaaeHTOM stoh nepe- CTpOMKH aaaaiOTca xpOMOCOMHWe aOeppauHH. ko* -'IHHeCTBO KOTOptiX V .1HU, KOHTaKTMpjTOUlHX C BX, aocTOBfpuo npeBhnuaeT xaHHhiH noxasaTexb b KOHTpojibHhix rpynnax (B. Teopmesa h M. UoHeBa; Heath h Dumont; Fleig h Thiess; Easier i Rohrborn). Hau6euu>uiee rbcjio xpo- mocomhux aPeppauHH Ha&moAaerea v jihu, noaBepraiOIlUIXCa B03,aeHCTBH10 BbiCOKHXKOHUeHTpa- QHfi BX a, K3K yKaauBaaocb Bume, hmuoiuhx HaaCanee BUpaHtemnie UMxyHHue HapymeHHH. C bthm xopomo coraacyeTca (paxT yseameKBa oKKoaornsecKOH aabaaeBaeMOCTE/ToabKO y jwn, noxBepraioiiiBxcB BoaaeiieTBBio! bhcokhx xohneHTpaaafi BX (B. C. OuztTQxa h coaT.; Ott B COBBT.). TaKHM o6pasou, Kate tUBHKxa. exaepoaepMo- noaopHoro cxBxpoua (chctcmhuh -<pii6po3, no- paxeHHe xoxb, cmupom PeiiHo. ^xpooereojuu), rax b KaHaeporeHHbtK d><peirr BX cxyjKax npo- a&aeBHBMH ojworo n Toro we --HMuyaonaTano* - rtraecxoro -- -spxpeKTa aaHBoro -aemecTBa. Ho- KaaaTeabCTBOM aroro noaowemui -cayatMT tpaxT . BOSHHKHOBeBBB 3KaiepHMeHTanbKUX reMBHTHO- capxoM y*e nocae pasBHTHB xam-HHu cHcreb- Boro TOKCHKO-BMiryBNoro nopaxeuR < cocyxos (Winell b cobbt.; Maricq h cobbt.). CjienyraniRM jtoxaaaTemcnoM naTOHMMyBHoro reitesa ony- -xanea npn BXB uryxstr aBMHS xnHHHSecxoH xapTHHW apyrax bkmvbhux -sadoneBaHHit -- dojanrax xuuiarai030B (H. I\ Tyeesa), jutn ko- TopHx xapaxTepHo lacroe ofirapyxeiuie ihtw- -ouepBux aHTBTM (C. H. HoBWaflocHft) h 6oaee -Bacroe paasarBenio -cpaBHeHHio c xoBTpoabuuMH "TpvnuauH onyxoaefi (H. T. PyceBar Tuffanelli a Winkelmanrr; jKreyaei . a cobbt.). Tlpouecc asaanoaeHCTBBX'-aKTHTejj c TKaHeBHMH amure- -maun nponxaer>--cROBBOM aa zaenax cochh-HBTOIXBOH TKaHH.-B-*iacmOCTH Sie*6paHaX cocy- nChob. -9to ofrbxcHxeT.'Tnoqejry nps 'BXB b nep- esyio -oqepegb -CTpaaaer coeaHHHTeabHas 'Txam. H TIOBOJIbHO Tacro BCJ3HHKaWT - CapKOMbl. 'r .'HpeaBQBKRBXB 3 2BBBOM ofiSOpe ^BMMyHO* ^BOXBMBBecxaB^cxeMa KaHneporeaoa -noa aeif- -crBBen BX .'xapaxrcpBa He tobbko jyu? xaopn- -poeaiiHHx BenpeaeabBux yraesoaopoaoB, tjo h ^fsornx apyrax ByrareBBUx Bemecrs.-Bee ohm, moaofiHo BX *okmhbikjt aaxHJiBpyiomee aeficr- -BHe (Koeman). ;JResyBbTaroi htoto jefteTBH -^BBjnercB -oppasdsaHiie emeciB c .aHTBreumiMH ~' CBOHCTB2MB. ,, B PATy_ - - J Aktohjotcchxo B. -A. SHHfLJixaopHjiHaH fiojieaab -- . "yraeBoaopoaHWH HeftportnccaKoa. TopbXBfi, -'=1980. Sacajuue Ai. a.Jip.-- Tar, Tpyaa, J972, Xfe 2, ,-.C-^4--27. 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HOBe mHpOKHX COUHaJIbHO-rHTHeHHBeCKHX B nepBtie we toah cymecrBOBaHHH h 'KnBHHBecKHX MccnejiOBaHHft pa3pa6a- . HHCTHTyT n3aBaTb Tpyju b cne- THBEJI MepOIIpHHTHH TIO 'O3fl0p0BJieHH}0 irsaJibHux -BHnycKax <03aopoBneHHe ycjiOBHH Tpyzta pa Gorhx. Tpyaa h peBO^KmHs? 6uTa, b hhx nena- TlepBbiM `jiHpeKTopoM HHcnrryra ~6nn Tairncb He-mabKo MaTepHajiu oGcaeflo- span B. R. Kohoiuwhkhh, paHee B03niaB- BaHHH paSJIHRHHX 4>a6pHK H 3aBOSOB, HO jihbeqhh <EBaHrejiHiecK3no-6ojibHHny>, b h nporpaMMH H3yReHHB ycjiOBHH Tpyaa KOTopofl b pa3Mecmncjr-OTCTHTyT. C ae- h Gtrra pafiorax, HHCTpyKHHH no H3yqe- jcafipa 1924-r. OTpeKTopoM -HHenrryTa HHIO COCTOHHHH 350p0BbB paGo'ClX H Jip. crajia-A. C. SoroJienoBa, yaeBHBmaH oco- no3we, 3 nepnofl HHflycTpHajiH3anHH 6oe BHHMaHHe pasBHTino u -BBenpeHHio CTpaHH, BbutexaioTca OTpacjieBbie rarHe- (C) <rHrHeHa rpyaa h op<x}>eccMOHaJibHue 3a6oneBaMnfl, 1983