Document NEwLZjBxDpJqqRK7arGkEqDLE

R&S 116885 \f G X. A. Makarov, K. I. Makarenko*: The Effect of Methyl Methacrylate and Vinyl Chloride on Hypophyseal Somatotropic Function** [0 vliyanii metilmetakrilata i vinidkhlorida na somatotropnuyu funktsiyu gipofiza] r[ AtM. i Sff Institute of Labor Hygiene and Occupational Illnesses, Gorkii Received June 16, 1982 Gigiena Truda I Professional NYE Zabclevania, 4: 32-36 (1983) ?*"-'I'm*"?. IqSS!** from Russian by the Ralph McElroy Co., Custom Division .02 Rio Grande, Austin, Texas 78705 USA R&S 116886 Code: 101-1479-2 THE EFFECT OF METHYL METHACRYLATE AND VINYL CHLORIDE ON HYPOPHYSEAL SOMATOTROPIC FUNCTION exposed to methyl methacrylate and vinyl chlo ride. Examination of workers engaged in chemi cal industry showed that many of them had paradoxical responses to insulin or glucose challenge, that may be due to toxic affection of the diencephalic region, and an abrupt in hibition of adenohypophyseal STH-production that also may be referred to the effect of these chemicals on the hypothalamus. As an example of the STH-inhibiting action of methyl metha crylate. the authors describe a case of acro megalia that ceased to progress as the patient started working in conditions of exposure to high concentrations of this ether. In a modern plastics plant methyl metacrylate (MMA) and vinyl chloride (VC) are widely used - toxic substances which have narcotic action. Long-term entry of them into the body is accompanied by development of a clinical picture of chronic intoxication, for which damage to functional structures of the brain is characteristic (V. A. Antonyuzhenko), including damage in the diencephalic region. We demonstrated earlier that this substance produces a pronounced somatrotropin-inhibiting effect (I. A. Makarov). However, it was still unclear what caused the pathological effect of MMA: action on the diencephalic centers or directly on the eosinophil cells of the adenohypophysis. The question of the specificity of this action also needed to be cleared up - is this inhibiting phenomenon inherent only to MMA or can it be produced under the effect of other industrial toxins? Page 2 Studies were carried out on 134 workers of the chemical industry and 24 functionally healthy people who had never worked in the chemical industry. The main group consisted of two subgroups. The first group included 100 workers from an organic glass (OS) plant, who were exposed to MMA, of which 51 suffered from chronic intoxication with MMA, while the second group consisted of 34 workers of a polyvinyl chloride (PVC) plant, of which vinyl chloride disease had been diagnosed in 26. Only the base level of the somatotropic hormone (STH) was investigated in the control group, while for the workers of the chemical industry, in addition to the base level, we investigated the concentrations of this hormone 30, 60 and 120 minutes after glucose loading (78 workers) or insulin loading (56). The glucose was administered per os (50'g). Insulin was administered in an amount of 0.15 U per kg body weight. STH in the blood serum was determined by a radioimmunological method with the aid of a diagnosis kit made by the Sorin Company (France). Along with the STH the glucose level in the blood was tested by the glucosoxidase method. The basal STH level of the control group was 5.4 0.2 ng/ml, which corresponds to the data of other reserachers (E. A. Vasyukova and A. M. Granovskaya-Tsvetkova; M. I. Balabolkin). The glucose level was 71.0 4.0 mg%. A reliable depression of the somatotropic function of the adenohypophysis was characteristic for the chemical workers (see table). An especially pronounced depression of STH output was seen in those suffering from occupa tional diseases before they had been removed from contact with the neurotropic toxins. The STH concentration was slightly higher in the workers without occupational illnesses, in the patients with those illnesses after they had ended industrial contact with MMA and VC, but the concentration nevertheless R&S 116887 Page 3 differed reliably from that in the control group. In spite of the fact that MMA and VC differ significantly in chemical structure (the former is an ester, while the latter is a chlori nated hydrocarbon), they produce approximately the same somatotropin-inhibiting effect. Evidently, this effect of these toxins is related to their nonspecific narcotic action on the central nervous system. An analogous effect has been observed for another narcotic substance - ethyl alcohol (Tamburrano). The STH and glucose dynamics during the insulin test and the glucose tolerance test is shown in the figure, from which it can be seen that administration of insulin is accompanied by an increase of the concentration of STH in the blood, which is evidence of stimulation of the eosinophil cells of the adenohypophysis, but even against a background of such stimulation the maximum level of this hormone did not reach the basal level for healthy people. The normal reaction, which was expressed in an elevation of the STH level during the development of hypoglycemia, was observed only in 32 of the 56 tested workers of the chemical industry, in 10 there was a paradoxical reaction consisting of a reduction of the STH level with a decrease of the concentration of glucose in the blood, and in 14 there was no reaction of the hypophysis cells to the changing glucose level. A gradual stable increase of the STH level as hypoglycemia became deeper was observed in 21 of the 32 patients with normal reaction, while in 11 patients the elevation of the hormone level was very brief, and was followed by a decrease of the STH concentration in the blood, in spite of the development of pronounced hypoglycemia. This brevity of the reaction of the adenohypophysis in workers of the chemical industry is evidently R&S 116888 Page 4 related to absence of reserves of this hormone in the eosinophil cells of this gland. The reaction in the form of an initial elevation of the STH concentration, which is then replaced by a drop of this concentration, was basically observed in persons suffering from chronic occupational intoxication with MMA. During the glucose tolerance test STH was not detected in any of 4 samples for 3 of the tested workers, paradoxical reactions were observed in 10 workers - an elevation of the STH at the same time as an elevation of the glucose concentration in the blood, in 23 workers the STH level did not change as the glucose level increased, and in 42 of those examined there were normal reactions consisting of a decrease of the STH level as hyperglycemia developed. In 4 patients, who were put in the group with a normal somatotropic reaction to glucose, the decrease of the STH level was preceded by a pronounced elevation of it in the peripheral blood. This elevation of the STH level was usually observed at the moment the ascending branch of the sugar curve became a descending branch and was probably due to a significant elevation of excitability of the nervous system, during which pulses from the glucoreceptors, which regulate the STH output, reached the adenohypophysis not only in the development of hypoglycemia, but even when there were negligible variations of the concentration of carbohydrates in the blood. This phenomenon was characteristic only for those patients with chronic intoxication with MMA. We do not have data on the direct effect of the investigated narcotic toxins on the STH-producing cells of the adenohypophysis. The noted depression of STH output under the effect of MMA and VC, the existence of frequent paradoxical reactions both to glucose and to insulin may be evidence of toxic damage to the diencephalic region in the development of chronic intoxication R&S 116889 R&S 116890 Page 5 by these substances. It is just this interpretation which other researchers give to the paradoxical reactions of STH to the indicated irritants (M. I. Balabolkin; G. G. Kyandaryan and A. S. Ametov; Wright). The degree of depression of the somatotrophic activity of the hypophysis under the effect of MMA and VC was practically the same, which is evidence of identical analogous toxic damage to the hypothalamus, while glucose or insulin loadings reveal a significant difference. A pronounced change of the STH level at the smallest variations of the glucose concen tration in the blood was characteristic for persons suffering from MMA intoxication, while pronounced variations of the glucose level did not cause a significant change of the STH index in those suffering from intoxication with VC. It is probable that this difference is due to the different action of these substances on the receptor apparatus of the vessels. Activation of the glucoreceptors, which control STH output, was observed in intoxication with MMA, while their activity was suppressed in vinyl chloride disease. The data obtained on the nonspecific STH-inhibiting effect of industrial toxins of narcotic action can be used as a sufficiently reliable and very sensitive criterion of chronic occupational intoxication. The soundness of using STH, and not some other hormone of the adenohypophysis, as an indicator of toxic damage to the hypothalamus is due to its unidirected only in a direction of a decrease of concentration - effect under exposure to industrial toxins. A phasewise type of toxicogenic changes is characteristic for other tropic hormones (thyrotropin, follicle-stimulating, luteinizing): first an increase, and then a decrease of their concentration in the blood, which sharply reduces the diagnostic value of these changes. R&S 116891 Page 6 We consider that a drop of the STH level below 2 ng/ml is a symptom of a pronounced toxic action on the nuclei of the hypothalamus. When the other neurological symptoms which are most often used to establish a diagnosis of an asthenic syndrome in combination with autonomic-sensitive polyneuritis appear, the concentration of STH in the blood is at the 0.6-0.9 ng/ml level, i.e., the changes of this hormone proved to be the earliest symptom which allows us to suspect occupational neurotoxicosis. It is striking that in nine-tenths of the people who had worked for long periods of time with these neurotropic toxins and who had not been diagnosed as having occupational illness, the STH level remained significantly reduced after they had left contact with these substances, which is evidence of irreversible organic microchanges in the nuclei of the hypothalamus, even though these changes could not be caught by neurological methods. The absence of complete normalization of the STH level in most of the workers with long lengths of service (without occupational illnesses) of the OS and PVC plants confirms our opinion regarding the very high diagnostic sensitivity of the method of determining the STH in the blood serum. At the present time, two neurological syndromes are used as the main diagnostic criteria for establishing a diagnosis of occupational illness: the asthenoneurotic and the astheno-organic, when there is autonomic-sensitive polyneuritis present (V. A. Antonyuzhenko). However, they do not always reflect the depth of damage to the subcortical centers. An investigation of STH in two groups of patients with occupational illness - with asthenoneurotic (35 workers) and astheno-organic (48 workers) syndromes - showed the very same concentration of STH in the blood serum - 1.1 + 0.1 kg/ml. In those cases where a more detailed study of the degree of toxic effect on the subcortical centers R&S 116892 Page 7 was needed' the determination of the STH proves to be more informative. An illustration of the STH-inhibiting effect of the industrial toxins of narcotic action is one of our clinical observations. Patient E., 40 years of age, entered the clinic on October 24, 1975. She had grown and developed normally. At age 17 she had begun to be troubled by severe headaches without visible causes, the features of her face began to enlarge, and her fingers began to thicken. However, neither the patient herself, nor her parents, who had noted these changes, paid proper attention to them. A year after the appearance of these symptoms she began to work as an instrument worker in the catalyst installation at an OS plant, where she was exposed to significant concentration of MMA. Some time after beginning contact with this substance the enlargement of the zygomatic processes and the nose and the thickening of the fingers stopped. At 21 she married. She had six pregnancies, of which two proceeded to term and four ended in abortions. In spite of such powerful stimulation of the function of the acidophil cells of the adenohypophysis, neither the facial features, nor her field of vision, nor her fingers began to change. At the beginning of the 1970s, after 14 years of contact with MMA, headaches appeared again and gradually grew in intensity. Later there appeared weakness, irritability, paresthesia of the upper extremities and shooting pains in the vicinity of the heart. Acromegaly of the facial features, a barrel-shaped rib cage, and thick thumbs were observed objectively. Craniography revealed enlargement of the dimensions of the Turkish saddle Page 8 (craniocaudal 15 mm, dorsoventral 18 mm) and an abrupt thinning of its posterior wall. Changes of the fundus of the eye and narrowing of the fields of vision were not observed. Taking into account the data of the sanitary-hygienic description of working conditions and the long period of work in contact with MMA, the absence of progression of the eosinophil adenoma of the hypophysis, we evaluated her complaints as the initial signs of occupational neurotoxicosis. Chronic occupational intoxication with MMA and eosinophil adenoma of the hypophysis in a phase of remission were diagnosed. The patient was transferred to work away from contact with MMA. In 1977 a significant improvement of her condition was seen in a dynamic control examination: the headaches had almost completely stopped, the weakness, irritability and pains in the heart had vanished. The STH level in the blood was 9.5 ng/kg. In a glucose tolerance test the STH concentration in the blood practically did not change, varying from 9.5 to 10 ng/ml. In a second craniography of the osteal accretions changes were not seen. Narrowing of the fields of vision was not detected. In our opinion, it was specifically the STH-inhibiting effect of MMA which was the reason for the cessation of growth of the eosinophil adenoma of the hypophysis in this patient. Growth did not resume even after six pregnancies, which often cause acromegaly to progress. The STH-inhibiting effect of MMA and VC , which we have established, is evidently related to their narcotic action on the hypothalamus, specifically on the ventromedial nucleus. R8tS 116893 R&S 116894 t Page 9 References [1] Antonyuzhenko, V. A., et al. Gig truda, 1972, No. 9, p. 19-22. [2] Balabolkin, M. I. Sekretsiya gormona rosta v norme i patologli [Secretion of growth hormone in the norm and in pathology]. Moscow, 1978. [3] Vasyukova, E. A., Granovskaya-Tsvetkova, A. M. Klin. med., 1977, No. 4, p. 124-127. [4] Kyandaryan, G. G., Ametov, A. S. Probl. endokrinol., 1978, No. 5, p. 37-39. [5] Makarov, I. A., Makarenko, K. I., Salmin, A. A. Endokrinnaya sistema organi2ma i toksicheskie faktory vneshnei sredy [The endocrine system of the body and toxic factors of the environment]. Leningrad, 1979, p. 134-135. [6] Tamburrano, G. et al. Cited in Balabolkin, M. I. [7] Wright A. D. et JL --Proc. roy. Soc. AtoL, 1970, v. 63. p. 221--22S. Page 10 STH and glucose dynamics when insulin tolerance and glucose tolerance- tests were run on workers exposed to VC and MMA. Time is plotted along the abscissa (in minutes): I - insulin tolerance tests; II - glucose tolerance tests; 1 - workers in contact with MMA; 2 - workers in contact with VC; continuous lines - glucose level; dashed lines - STH level. 9689 W Page 11 Base level of STH in various subgroups of examined workers. STH level, ng/ml Subgroup_____________________ MMA__________ VC Persons suffering from occupational illnesses who have not been taken out of contact with the toxic substances 0.70 0.10 (24) 0.80 0.26 (9) Persons suffering from occupational illnesses who have been removed from contact with toxic substances 1.46 0.39 (27) 1.23 0.25 (15) Persons in contact with industrial toxins 2.18 0.60 (33) 1.30 0.50 (10) Persons who were in contact with industrial toxins in the past 2.34 0.71 (16) Note. Number of examined people indicated in parentheses. R&S 116896 HTOe HAfi^aronpaHTHoro bahahhh H3BOactbeHaofl cpeAW, TeM 6oJieearo B rpynnax pafioHHx, noABepraBuraxca B03AefiCTBHK) MBHee BhICOKOfi KOHUfcHTpa- shh BX, kotoptie mojkho CTOTaTbf rpyn* naMB BHVTpeHHero KOBTpojiH, 3a6cpieBaeMOCTb 3.'I0KaHeCTBeHHbIMH H0B0a6pa30* BBHBBMZ KHJKe, 4eM CptttH HaCCJieHHB. npEUCHZB JHCnepCBOHHblfi aHaAH3, HaM yaajiocb bhhbhtb AacroBepHoe /bahhhhc BX sa aacTOTy 3A0KBHecTBeHHMX hobo* o6pa30BaH3fi (i5<0,0Ql). / PeayjtBTaTBi HCCjiaaoBaHHa /iio3boahah peKouesjOBaTb aah BHeApeaka b npaK* THKy ueponpHBTBB, HakpaB^eHHBie Ha B. C. --!B joj.: TnrHeKa h TOKCHKOJionw bw- coKOMOJiacy.'iapRUx coeaHHemia h XHMime cxoro cusbfl. JI., 1979, c. 288--289. Crush J. L.. 'Johnson M. N. -- J.' occup. Me 1974, V. 16\p, 150--151. /ox A. Cottier /. /. -- Brit. J. prev. Joe. Med, 1976. \v. 30, p. 225--230. Lee C. C, Bnhndare I, C, Winston If M. et al. -- Envirpnm. Hlth Perspect, /1977. v. 21, p. 25--32. / 77wo T,, ffneen A ripHMeneHHe anKAeitHOAorR* vecxttx MeTOAOB\npH nsyaemiH HenH<J>eKHHOH* Htix aaOoAeBassa. M, 1965. / Maltoni C, Leftmink C. -- Environm. Res., 1974, v. 7, p. 387--405A / Tabershaw- /, R., Gamy IT. R. -- J. occup. Med., 1974, v. 16, p. 509+518. ll. et al. -- Tomatis L, Agthe u, Bartseh yaynmeHHe ycnoBHft Tpyia k apoh3boa- Cancer Res, 1978, V. 38, p. 855+877. ersax BX a nBX. \/ Bubo jib. 1. ycTaHOBJiefeo AocroBep- Hoe BZHHHBe BX Ha aacTOTy 3JioKaaecT- BeHHbtx H0B006pa30BaHHfi j y pafioTaio* max b npoH3BoacTBax / BX h IIBX Waxvtiller R. Stringer W., Wagoner 1. K. et al. -- Ann. N. Y. AcadL. ScL. /1976, v. 271, 40--48. / ndcrymcjM I9.01.SJ THE INCIDENCE OF .ignInt TUMORS (P<0,001). /\ AMONG WORKERS (GAGED IN THE 2. Haz6o.T>mBfi ypOBem, saooJieBae- MANUFACTURE OF VII CHLORIDE AND MOCTH 3.10EaBSCTBCHHbIMB HOBOO(jpa30Ba* POLYVINYL CHLORIDE. Fedotova hhhmh 3aperHCTpHpoBaH/B rpynne^pafio-. hex, no^BepraBmaxcB a(03AeficrBHia bh- Epidemiologic survey of \ tie incidence of malignant tumors in 3 groupsyof workers vary COKOH KOHBeHTpaOHB B^C. \ ing by the degree of exposureyto vinyl chloride 3. HaafioJiee cyrnecrBeHHHe no cp^B- (VC) has revealed increased incidence of wtmo c EaceJieHBeif /pa3JrHTOH ypoB^-DaesaeMocTB onyxoJiBMH otaabhc Ea.iH3amiH HafiAraiawrcji ajib pana\ tumors in the group of subjects! working in the most adverse conditions, characterized by a high concentration of VC in the air of work site. The influence of VC oiythe incidence of onco 'AiZ.-iy3.K2. V JKeHfflHH H 3AOKaBeCTBeHHblX logic diseases was found to be significant HOBOo6pa30BaHHH JIHM^aTHBeCKOfi H KpO- k(P<0.001). Pulmonary /arcinoma. malignant BeTBOpHOfi TK3HH AAH 060HX DOJIOB. iplasms of the lymphatic and \ hemopoietic tissue occur among males of the examined group more often than among the population JIHTEPATyPA at lakge. In women Abe incidence bf gastric carcinoma and malignant neoplasnu of the ZoaupuH B. 3. -- B Ike.: SmuLeuHonontx pass lymphatic and hemopoietic tissue is\ signifi a crpanax C3B. M, 1979, c. 55--86. cantly higher than/ among the population at Ctob6?p H. H., KypAfiJidciam 5. A., Typycoe large (P<0!05). VAX 6I3.S32: |M7.391J*r7.743AIl*O7:*l2.4S3.eS.01S H. A. MAK.4POB, K. H. MAKAPEHKO O BJIHRHHH METHJIMETAKPHJIATA H BHHHJIXJlOPHflA HA COAUTOTPOnHyiO #yHKUHK) rHIIO<l>H3A HsCTBTyr mmenu Tpyaa a npo^safioneBaHHfi, r. ropbXHA B COBpe.MeHBOM npOH3BOACTBe TIJiaCT- Macc HaxojHT mHpoKoe npHMCHEHHe MeTH.TMeTE KpHJI 3T (MMA) H BHHHJtXJIOpHA (BX) -- TOKCHBHue BemecTBa, 06AaAaroiUHe Hapkothtcckhm AeflcreHeM. HHHTeAbHoe nocTynneHHe hx b opraHH3M pa6o>iero conpoBOJoaeica pa3BHTHeM KJIHHlReCKOft KapTHHbl XpOHHBeCKOfl HHTOKCHKaUHH, J.1H KOTOpOH XapaKTepHO sesEe (JjyHKnHOHa.ibHbix crpyinyp BKoro Mora (B. A. AHTOHiojKeHKo), B TOM EHC.ie H AH3Hnecf)aAbHOH OfijiaCTH. PaHee HaMH 6ujio noKaaaHO, bto sto BemecTBo AaeT BbjpaxceHHbiR coMaTOTpo- nHHHHTHfiHpyiomHfi 3t})4)eKT (H. A. MaxapoB). OflHaKO ocraBajiocb HeacHo, uesi ofiycJioBJieH naTOJiorHwecKufi 3<J>4>eKT MMA: AeflcTBHeM Ha AHSHue^ajibHbie IieHTphI HJIH HCnoCpCACTBCHHO Ha 303HHO<J)HAbHbie oeTKH aAeHorHno4)H3a. HyHtAaACH b yroBHesHH h Bonpoc 0 cneaH4>HHHOCTH AaHHOTO A6HCTBHfl -- CBOflCTBeH AH 3T0T HHTH6HpyiOmHH ^^HOMeH TOAbKO MMA HAH efO MOJKHO nOAyBHTb 32 Gigiena Truda I Professional NYE Zabclevania, 4: 32-36 (1983) OpB ACHCTBHH APJ aAOB. Met HHB n BHX X npaKT Hefl h 30 to2 n S 3A0P V) raBm: COCTOfl ! hoa AHAO cTeicna O) 00 5oeh; noa CTBHXJ cKofl h: (O ^4 H3 K :aAH' 34 pad DOH3 XAOpHA i).i HOCTHpOBaHa BHHE B KOHTpOAbHOfi IT CaaaAbHbifi VpOB< ropMOHa (CTT), - XHMHBeCKOfl npOMl 6a3aAbHoro ypoBB SeHTpaSHIO A3HH0 60 h 120 uhh noc: (78 bcaobck) hah BeK). rAK)K03y (50 r). HHCyAHH 0,15 EH Ha 1 et pOTKe KpOBH onpe HUM MeTOAOM C U MOB 4>HpMbI Sori BpeMeHHo c CTr KOHseHTpaiiHio r. Aa3HbIM MeTOAOM. y AHA KOHTpOA Hbtft ypoBenb CTI ht/ma, tto cootbe rax aBTopoB (E. . Tp aHOBCKaa-IXbcti khh) . KomxeHTpan Aa 71,04,0 Mr % HeCKOH npOMWIOAE TCpHO AOCTOBepHO TpOnHOfi (JjyHKAHH TafiAHay). Oco6ei AaBAeHHe Bbipafim y SoAbHbix c npod AeBaHHHMH AO BUI Ta C HeflpOTpOHHH 6e3 npocfteccHOHaj fiOAbHbIX C raKHMI Ae npeKpameHH. KOHTaKTa c MMA CTF 6biAa HecKox MeHee AOCTOBepHO 33TeAefi B KOHTpOJ pa Ha to hto MM. pa3HETca no xh (nepsbifi -- 3<|)Hp,: Htifi yrAeBOAOpoa) TeAbHO OAHHaKOB THfiHpyiomHft 3<t> 3T0T 3<|)4jeKT )rK22 R&S 116898 ape ae&CTBHB spyrsx npouwiuieSEux haob. HcorwoBaHHa npoBeaeHH y 134 pa6o- HHX XHMHieCKOfi npOMbmiJieHHOCTH h 24 UpaKTHHeCXB 3AOpOBbIX AHA, HHKOnaa B Heft ne paCoTaBtuax. OcHOBHaa rpynna cocToaaa H3 2 noArpynn. B nepByw bxoahao 100 paCoHHx npoH3BOACTBa oprcreiuia (OC), noABepranmHxcfl B03AefiCTBHK) MMA, H3 KOTOpHX 51 C XpOHHWeCKOfl HHTOKCHKaHHeft MMA, BO BTOpyiO-- 34 pafioanx npoHSBOACTBa aoahbhhhaxaopHAa (IIBX), H3 kotopux y 26 AHarHOCTHpOBaHa BHHHJIXAOpHAHaa <50Jie3H>. B KOHTpoJibHoft rpynne H3yiajiH tojibko 6a3aAbHUH ypoBeHb coMaTOTpoiraoro ropMOHa (CTr), TorAa xaK y pafioaHX XHMHHeCKOft npOMhIIIIAeHHOCTH, ' IIOMKMO 6a3aABHoro ypoBHa, HccAenosanH kohneHTpanHio ashhoto ropMOHa aepe3 30, 60 h 120 mhh nocjie Harpy3XB rnioK03oft (78 aenoseK) hah HHcyAHHOM (56 aenobhk). rAWK03y A3B3AH nepopaAbHO (30 r). HHcyAHH bboahah H3 pacneTa 0,15 EJI Ha 1 kt Macon. CTr b cbibopOTXe KpoBH OnpeAeAHAH paAHOHMMyHHbLM ueTOAOM C nOMOlAblO AHarHOCTHKyMOB <|)HpMH Sorjn> (C>paHHHH). OahoBpeMeHHO C CTT B KpOBH BCCAeAOBaAH KOHnejrrpauHK) rnjOK03M taioko3okch- AE3HHM MeTOAOM. y aha KOHrpoAbHoft rpynnbi 6a3aAb- Hbift ypoBeHb CTr paBHHACa 5,4;fc0,2 Hr/MA, aro cooTBercTByeT A3hhhm spyrax aBTOpoB (E. A BacioKOBa h A. M. rpaHOBCKaa-IXBeTKOBa; M. H. Baaa6oA- KHH). KOHneHTpaHHH rAMK03bI COCTaBAa- Aa 71,04,0 Mr %. Rjih pa6oanx xiimhaeCKoft npoMbiuiAeHHocTH Cbiao xapax- Tepso AOcroBepHoe noAaBAeHHe coMaTOTponHofi (Jjvhkahh aAeHorHno(pH3a (cm. rafiAHuy). OcofieBHo BbipaaceHHoe no AaBAeHHe BbipafiOTKH CTT HadAIOAaAOCb V fiOAbHbtX C npO$eCCHOHaAbHbIMH 3a6o- AeBaHHHMH AO BbtBeAeHHH HX H3 K0HT3K- Ta C HeftpOTpOnHbIMH HAaMH. y paOOHHX 6e3 npo$eccHOHaAbHbix 3a6oAeBaHHft, y OOAbHblX C T3KHMH 3a60AeB3HHaMH nOC- Ae npexpameHHa npoH3BOACTBeHoro KOHTaKTa c MMA h BX KOHueHTpauna CTr 6 aa a HecxoAbKo Bume, ho TeM He .\:eHee AOcroBepHO oTAHaaAacb ot noKa- 3aTeAeii b KOHTpoAbHoft rpynne. HecMOT* pa Ha to hto MMA h BX cymecTBenHO pasHHTca no xhmhhecxoMy CTpoeHHio (nepBHft -- 3(pHp, Btopofi -- XAOpHpOBHH- hbih yrAeBOAopoa), ohh aarot npHfiAHSH- TeAbHO 0AHH3K0BHH COMaTOTponHHHH- mfiHpyiomHft 3$$exr. rio-BHAHMOMy, 3TOT s^xpeKT yxaaaHHbix haob cbh33h c Eu&nbHuft vpoBCHw CTT 8 puahihux noarpynlux oficneaoBXHHUX paCoHHX Hoflrpynn* ypoieMfc CTT, Hr/iu MMA [" EoJibuie npo$ec< CHOBUbHUdB 3a60JieB2HHHMH, Be BUBtaeHHue B3 KOHTaKTa C TOKCHHHblMU BmeCTBBMB BoabBbie npo<|)ecCBOBUbHUMB Sa60JlCBaHBHMH, BUBeaeHBbie B3 KOHTaKTa e tokCBBHUMH BemeCTBSMH JlBSa, X0HT3KTH* pyniBHe c npoMbtnxaeasbiuB UflMB Jlxna b npomaoM KOHTaKTHpOBaBmBe c npoMumaeBHMMM XABMB 0,700.10 (24) 1,46*0,39 (27) 2,18*0,60 (33) 2,34*0,71 (16) 0,80*0^60) 1.23*0,25 (15) 1.30*0,50 (10) npEt/eviHut. B cxoCxix yxassHO bhcbo 06cneAOBaHRbDt. HX HecneUH^HHeCKHM HapKOTHHeCKHM AeftcTBHeM Ha neHTpaAbHyio HepBHyio- CHcreMy. AHaAorHHHoe AeScrBHe Hafinio- AaAOCb b y Apyroro HapKOTHaeCKOro Be- mecTBa -- sthaoboro cnHpra (Tambur- rano). ilHHaMHKa CTr H rAK3K03bt npH npoBeAeHHH HHcyAHHOBOft npo6u H Tecra TOAepaHTHOCTH K TAIOKOSe ITpeACTaBAe- Ha na pncyHKe, hs KOToporo bhaho, hto BBeneHae HHcyAHHa conpoBoatAaerca POCTOM KOHneHTpaAHH CTr B KpOBH, CBHAeTeAbCTByjomHM o CTHMyaanaH bo3hho4>habhhx KAeTOK aAeHorHno$H3a, ho aaace Ha (pose TaKoft crnntyjixjxm hbkcbMaAbHuft ypoBeHb ropMOHa He Aocraraer 6a33AbHoro ypoBaa y SAOpoBbtx ahu. 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B 1977 r. npH aRHaMHiecxoM xoHTpoabHOM o6caeaoBaKHR omexaaocb ismmtiuMot yayamexHe coctoxrrh GoabHoA: norra npexpaTKancb roaoBHue 6oaK, HcnesaH caaGocrb, paaapaxtHTeabHOCTb h 6oah b cepaue. ypoBeHb CTF xpobh 9,5 Hr/xr. npa npoBeaeHRR TecTa roaepaHThocth x ramose xoHueHTpauHR CTr b kpobh npaxTHHecxH He H3MeaRaacb, xoaefiaxcb or 9.5 AO 10 Hr/M.l. npx nOBTOpHOA KpSHHOrpatpHH HSpacTaHHfl koctrux HaMeneHiift He oCHapyxceHo. CyweHHft noaeft 3peuRx He BURsaeHO. no HarneMy mkhhio, hmchho CTT- HHrHfinpyioiuee AeflcTBHe MMA 6mjio npHHHHofl npeKpameHHH pocra so3Hho- 35 aaeHOMw rHnot})H3a y , stoS 6o.ibHofi. Poct He bo3o6hobjihjich naxte nooie 6 OepeMeHHoerrefl, Hacro npoBoiiHpjTOiuiuc nporpeccHpoBaHHe axpoMera/IHH. ycTaHOB-ieHHoe hsmh dT-HHrHfiHpy* jomee B-iHSHHe MMA h BX, no-BHUHMo- My, C3H33H0 C HapKOTHHeCKHM ACHCTBHm hx Ha rHnoTajiaMyc, b h3cthocth Ha BeHTpoMe^BajibHoe sapo. /IHTEPATyPA Ahtomoxbhko B. A. b ap- -- Tur. Tpyaa, 1972, J& 9, c. 19--22. ojul6oakuh M. H. Cexpenna ropMoaa pocra b aopMe h naTcuioniH. M., 1978, BaaoKoea E, A., rpaHoecKax-IieeTKoaa A.M.-- Kahh. v.ej., 1977, N> 4, c. 124--127. K-itidapnH r. Ambtob A. C. -- IlpoGA. shao* xpHHo.'L, 1978, J6 5, c. 37--39. Manapoe H. A.., Maxapenno K. H., Coxmuh A. A. 3aA0Kp:fEKaa CHcreMa opraHH3xia h TOKCHve- cKHe ({jaKTopu BSeniKefi cpem. JL, 1979, c. 134--135. Tamburrano G, et al. -- Uht. BanaGoAXHH M. M. Wright A, D. et al. -- Proc. roy. Soc. Med., 1970, v, 63, p. 221--226. noctyniwi 16.0G.SB THE EFFECT OF METHYL METHACRYLATE AND VINYL CHLORIDE ON HYPOPHYSEAL SOMATOTROPIC FUNCTION. /. A, Makarov, K. /. Makarenko The basal STH level and its time course were studied in insulin or glucose tolerance tests in 24 normal subjects and 134 workers exposed to methyl methacrylate and vinyl chlo ride. Examination of workers engaged in chemi cal industry showed that many of them had paradoxical responses to insulin or glucose challenge, that may be due to toxic affection of the diencephalic region, and an abrupt in hibition of adenohypophyseal STH-production that also may be referred to the effect of these chemicals on the hypothalamus. As an example of the STH-inhibiting action of methyl metha crylate, the authors describe a case of acro megalia that ceased to progress as the patient started working in conditions of exposure to high concentrations of this ether. yjlK $13.632:S47.338.14]]-036.S( MBA) H. C 3JIOBHHA, B. B. BPJKECKHH OTfiAJIEHHblE IIOCJIEflCTBHJ! flEHCTBHJI CTHPOJIA (0E30P JIHTEPATyPbl) HHcmTyT rHTHeHU Tpyaa h npo<f>3a6oAeaaHHH AMH CCCP, Mocxaa Bosmojxhoct* OTxaneHKHx nocaexcTBHft bosAhctbhs cmpona H3yqaaacs s npoaaaoAcrae h a ycsoBHXx sxcnepHMeirra. noxasaHo, rro np aupafioTxe CTaBAapTOB npeaeasHO AonycrHuux KOHAeHTpauiifl aaa Tepanreiuaix coeAHaeHHfl seaecoodpasHo ycTasoBim tioaee nmpoxHe npeAeau 6e3onacBocTH (K. Xcmmhhkh). Cthpoji bbpaay c BeKOTOpHVfH MOHOitepaMH Bomea b xaTa.ior TepaToreuxbix areHTOa (Shepard). reneTHvecxoe AeficiBae crapcuia Hjyvanocb y AAHTeAbKO padOTaiOZIIBX B npOHSBOACTBC npn bucokom coAepacaHRB crapoAa b Bosayxe. Tax, B np0H3B0ACTBe CTtKJlOnJiaCTBKOBhlX BSAeAHft Ha ocHose no.mB(pHpHfaix cmoa npH xoHneHTpaarax CTHpo-ta, paBKHX 200--300 ppm (Meretoja H coasT.), b Ky.ikType ahskPouktob 16 padoiHx HacTOTa xpomocomhux adeppanafl (XA) cocraBH.ia 10--26% (b KotrrpoJie Be npesumasa 4%). HaH6oJiee ramruibiMH HapymeHHHMB Ghah paspaiBU xpomocom. 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Ha&noAaABCb 2 rpynnu pa6oTaiomHx npH cpeAHefl KOHueHTpamtH crapo- aa 137 h 1204 ur/tt*, a Taxace xoKTpoJibHue Jiaua. HaftaeHH cymecnesHue pa3JiHVHa b aa- CTOTe XA epeAH SKCnOHHpOBaHHbfX H KORTpOAbHbIX AHU (COOTBeTCTBeHHO 7,9 H 3^%). He OTMeaeHO pasAHHHfi tiexuy CpeAKHMK BeAHHHHailH XA b rpjTinax. Ho b nepBofl rpynne OuAa ycraHOBAeHa 3aaHcifMOCTb HapacraHHH vacTom XA or cTaaca pa6oraK>uuix. BoSMoamocTb xaHueporeHHOro pncxa npocae- HteHa na pafioaHx b npoasBoACTBax noAHcropcaa h cmpoA-6yT3AHeHOBoro xayxyxa. HMexrrca AaaHbie, cBHAeTeAbCTByJotUHe1 o xaKneporeHHofi onacHOCTH cmpoAa, nposBAaiomeHca b AenxeMB- ax n AHM0oxax (y 6 u 140 aeAOBex b npoxs- BOACTBe cmpoA-SyraABeHOBoro xayayxa). B 1978 r. onydAHKOBaHbi AaHHbie o AAHTeAb- SOM RadAlOAeHHH 3a padOTHHKaMH, XOHTaKTHPOBBBUiiiMH co cmpoAOM (Nicholson H coaBT.). Hs 560 pa6o<iHX co cTaxeM paCo-ru b npoHSBOA- CTBe noAHCTHpo.ia He MeHee 5 act, bshtbix doa HaC.noAeHHe b 1960 r., b 1965 r. npoAOAacsab pafiOTV 233, vuiah c npoHSBOACTBa 241, ywepah 83. OacHAaeMaa CMepmocTb 6nm 106,41. Pax 6ua npHHHHofl CMepTH 17 aeAOBex, b tom iHCAe y 1 or AeftxeMHH (/IK) h y 1--ot ahm(jiOMbt (/Id)). Hs 21 cnyaaa 3aperHCTpHpoaaHHOH CMepm y paOoaitx, ymeamux c npox3BOACTBa Ao 1960 r,, y 1 npHumoii 6um /IK, y 1 --/Id) H erne y 1 -- coaeTaHHe /IK c HiueMHvecxoH 6o* AesHbx> cepAtta. Ha 444 cnyaaes cmepm padohhx, Koraa-TO npopafioTaBuiHX b btom npoxSBOA- /: cnt 6o.iee 6 xec, 5 -- sadaiesasKa . Av^eHHue AaxHxe, TeAbCTByfOT O 303) npn paGore co cm Pha HccneAcsa' Heniis Ckhabhahh b2ah pesyAbTaru HID*: npH B03AEXCT MeTaOoAKaxa ero i B 1978 r. (Lin: BKbi pesyAbtaru a okjich cmpaia KAeTKH BepxynievKi oueHHBr -!!![: h ero ra ABKO ( 3" cresiax UK70TC me, cm pa new c B TO 3BT.) 33 Tyj b 01 CO Aa. res ^ 'aige Ql A HS (O iax>m utecT ta. 1 ABT O r ot iba n crept cxo; H 0.___ jrroret mpoia (Meretoja n cobbt. ays APoaofpKAy pa: HTO CTHPOA Hecxc oxncb cmpoaa ( CLw cocraBAHAo 5( BaHHH HHCTblX HpE KOHTpoAe.v o6a sen utesHe peueccHBHMx fpRAbHofl Moaena ( HTO CTHpOA He B! BbtX XPOMOCOM. Kpc HacroTy khkpoxaep XHTaficXHX XOMHVKO Kankaanpaa a c ycTaHOBAeHo, <rro e TpKXAopnponaH, mo hoi: mCeAi! 3apoAbi HOe II SMfipHOTOKCE okhcu crapaia. Cmpoa Aerxo nt porno pacmopHM b npcHHxaTb vepe3 n. 3A0GHna; Elovaara ABT.), nOSTOM)' occ HCCAeAOBaHHH XA : Bpeua GepesieHHOcn hmx CAacrv.acc, h p pacre ao 20 Mec. Aj vecxH AOCTOBepHbie HapymeHHsx, tto. n TeAbCTBOBCTb O H2C cm K XpOMOCOMEHM ca CAeACTBiieM bosx GepeweuHocTH (\'ain: KaHueporeHHOe a Meme HayTianocb cayxax Mxuieif x: GepeMeiiHOCTii bboah 3ax nepopa.UHo. J'c TaAbHaa c.vepiEocn BOTHbiM oGoero noAa we Aose. Taxace c HOCTb nOTOVCTBa. Pe icii mokjv nojonuT bothmmh hc ycraxoi nr 1931 r. ilICKOi ;fcHJtaeI. 'exia Tpyaa )0. Ha ocEose m B B-1HETT>mJr 3aTtpesanpfl- i-TpyioBoi cc,' ycra- jafpeccHefi. iarHoeraxn 1- 0OpM8X i-n.5eBHe esux cy* iQSBfc .msTB3K Tpy- iHBHTpai) oik rA, La, DOL- rSKAYA, IITSOVA. | momentrk enviterprises I. Phy. c factor ,L LA., id pbyjonomic | ie tools A. I., rization I ditions, 1 's, and , UZU'ERNE* ent of -garian NTYE* | motion `omen I motion contacarciration ife-gaefe'd OEUOTOBA H. B. 0 pacnpocrpaHeHHocnj MOKaieCTBeHEMS H0B006pa30B*HHfl cpejH pafioiHX, saHATUx a npoHaaoacraax bhhilixaop&aa h natuBHUHAxnopRAa MAKAPOB H. A, MAKAPEHKO K. H. O ukxkkk MerBaMeraxpanaTa bhhr.tuiopiua hb cOMaTorponHyw ^juxnrno ntnoipiiaa 3J10BHHA H. C, BP5KECKHH B. B. Oraa^eHHwe nooieacTBHa aeflcrsHa crepoxa (063op AHTCpaTypU) 30 FEDOTOVA, I. V. The incidence of mali gnant tumors among workers engaged in the manufacture of vinyl chloride and polv* vinyl chloride 32 MAKAROV, I. A.. MAKARENKO, K. I. The eifect of meihy] methacrylate and vinyl chloride on hypophyseal somatotropic fune* ' tlon 36 ZLOBINA, N. S., BRZHESKY, V. V. Late results of styrene effect (review of litera ture) KpaTKHe coofiuteHHa Brief Communications KHPHJIbHVK n. n,, HABAH H. M. Ycjiobhb Tpyaa h HexoTOpue (pH3HOJiorHiecKiie noKa3Tejin y pafioHKX xxeJie$a6pHX 38 KIRILCHUK. P. P., CHABAN, 1. M. Work ing conditions and some physiologic para meters in workers of hop factories KJIHMEHKO T. JL, K03J10B M. A-. J1IOTOB A. H,, MHPOIHHHMEHKO A. B,, CABEHKOBA H. E. CocToxRHe <pH3Haton<<te* CKHX (pyHKEHft y padOTHBO, aaKHTUX 3pHTe.ll>* HO-HanpHMteHHMMH BHJtaMH pafior npH Heau* COKOM ypOBHe ABBTaTeJUtHOfi aXTHSHOCTH 40 KLIMENKO, G. Ya.. KOZLOV, M. A., LYUTOV, A. L MIROSHNICHENKO, A. B,, SAVENKOVA. N. E Physiologic functions in female workers engaged in work involv ing vision exertion and low levels of motor activity MHXEJIbCOH R. A, BHHOTPAflOB C. A. IlyTH npotpunaKTHKH jioKajiBHux oxxawae* hhR pudoodpadOTiHKOS aa cyaax 41 MIKHELSON. D. A., VINOGRADOV, S. A. Approaches to prevention of cooling of workers of factory ships KAPHAyX JI. A. OnTHMHaauHH Tpyaa MaBtRHHCTOB anexTpoMOCTOBiu xpauoB uexa odacKra oxaramefi 43 KARNAUKH, L. A. Optimization of work of electric travelling crane operators at pel let calcination shops rPHHEBHH B. A. K Bonpocy o TpeHHpoBxax opraHH3Ma HexoBexa b ninep6apH<jecxHX yCJIOBHHX 45 GRINEVICH, V. A. Training of the human body under hyperbaric conditions T5TPEHH E B., AJIUbtPEBA M. B,, MHJI- 46 TURBIN, E V., ALDYREVA, M. V,, MIL- KOB JI. E H3MCHeHue HexoTopizx noxaaa- . KOV, L . Changes in some nervous system re-iefi HepsHoft chctsmu y pafioTaioiHHX b characteristics in workers exposed to phtha- xoHTaxre c (praviaTHUMH sJiacrHcpttKaTopaMH late plasticizers 3PMAH M. H., EAyMAHE M. 3, CJIHHbKO B. H, yCTHHEHKO A. H,, BEPHH r. E, KPACHOKyTCKAH JI. M. OcoSeRHOCTH CaHHTapHofl CTXHABpTH3attHH aap030AH xapfioxpoMeaa b Bosayxe pafiovefi 30HU IipOH3BOACneHHUX nOMtmeHHft thtjihha a. r,, itceb c. a, bpioXOBEU T. r. MopipcmonnecKHe K3MeHeHHH OpraHOB 3KHBOTHUX, ROABepraBIUHXCX HHra.IHuhohhoh 3arpasKe skphahhtphaom rA3EAPOBA H. H,, POEHHKOB A. B,, apohoba e. h,, mys o. a, tapiueHHH B. O. rHTBCHHiecKSH oneHxa iibt3hhx Pat fioTHHKOB nhaByHHX Oypoaux ycraHOBox K'ai cDHftcxoro PacceitHa HHtpopMaoHH coseTCXoro ToxcHxoAoniBecxoro ueBTpa 48 ERMAN, M. I,, BAUMANE, M. E. SLIN- KO, V. N,, USTINENKO, A. N. VERICH, G. E. KRASNOKLTTSKAYA, L M. Features of sanitary standardization of earbocromen aerosol in the air of enclosed work environ ment 50 GITLINA, A. G., GUSEV, S. D., BRYUKHO- VETS, T. G. Morphologic changes in the organs of animals exposed to aery] nitrile inhalation challenge 52 GAZDAROVA. I. N., RODNIKOV, A. V.. ARONOVA, E. N,, SHUB, 0. A., GARSHE- NIN, V. F. Hygienic evaluation of nutrition of workers at' the pontoon drilling rigs of the Caspian sea 54 Information of the Soviet Toxicologic Centre XpOHHKa I1AHKOBA B. B. Bcrpeva c BetepaHaMH TpyAa Current Events 59 PANKOVA, V. B. Meeting with work vete rans PeueH3HH HTJ130BCKHH T. A. PeueH3HB a KHHry P. B. BopHCCHKOBofl. HirHexa TpyAa npH ao6une no.ie3Htot HcxonaeMbtx otkputum cnoco6om. M,, MeamiKHa, 1982 r. 176 c h.i.i. Book Reviews 59 GUDZOVSKY, G. A. Review of the book by R. V. Borisenkova. Occupational hygiene in strip mining of mineral resourses. Moscow, Meditsina Publishers, 1982 63 MKHKCTEPCTBO 3APABOOXPAHEHJIH CCCP BCECOK33HOE HAV'IHOE 06WECT80 niniEHHCTOB rMFMEHA OCHOBAH B 1957 POAV AnPEJlb 1983 u npo^jeccuoHaAbHbie 3a6oAeB aEQfl 4 MOCKBA -MEflHUHHA- EmcMeciHKuft KayMHO-npaKTHNeomii *ypHaji yflK 612.755.1 B. B. P03EHBJIAT PABOTOCnOCOEHOCTB HEJIOBEKA H tlPOEJIEMbl EE nOBbllUEHHSl ypa.n.CKHii jiecoTexHH^eoasa hhcthtjt hm. JleHHBCXoro Komcomoab, CBepjuioacx tripofijieMa paCoTocnocofiHocTH ejio* sa saHHMaeT BaxcHeftuie Mecro b <j>H3H* oniH h ranieHe rpyAa. nPH paCCMOTpeHHH nOHHTHH pafiOTO- cnocofiHocTH cjieayeT npHHHTb onipaBHoe onpeaMeHHe, nocKOJibiqr ejHHOH toikh 3peHiia 3aecb erne HeT. no Hameiiy mhc* hhjo, HaHfiojiee npaeMxeMO cxeAyromee onpeae-ieHMe, pafiOTOcnocofiHOcn. -- Be- .IHVHHa dJVHKHHOHaJIbHHX B03MOJKHOCTefi opraHn3Ma, xapaKTepH3yioinaHCH aipipeKTOM MaKCHMa.lbHOrO yCHAHH, HAH, IIOXHee, KOJiH'iecTBOM h KanecTBOM pafiOTbi npn KanpstHceHKH mbkchmajibhoA HHTeH* CHBHOCTH HJIH JJIHTeJILHOCTH. HflyMS COCTaB.isiom.HMH ee hbxhiotcs MaKCHMaxbHO B03M0JKHbie 4>H3HOXOrHHeCKHe 3aTpaTbI H SljHpeKTHBHOCTb 3THX 3atpaT. ripoHJi.iiocTpHpyeM cKa3aHH0e Ha npaMepe 0U6HKH 4>H3HHeCKOfl pafioTocnocofihocth. Ha rrpaKTHKe Hcnoxb3yeTca Asa noxxoaa, KOTOpue hctko cooTBeTCTBywT AByM Ha3BaHHbiM cocraBAjnomHM pafiotociioco6hocth: 1) onpeAexHioT npeAexbHble ypOBHH q>H3H0J10rHHeCKHX 3aTpaT nyreM H3MepeHHH MancHMaxbHoro notpefi.ieHHH 02, 2) onpeaexHiOT 34>t|>eK- THBHOCTb <J)H3H0A0rHH6CKHX 3aTpat (KaK 6hi KIW opraHH3Ma) hh ocHOBe h3Bhct- TecTa PWCito. 3th noAxoAH hhotFnpOTHBOnoCTaBJIHKITCfl, MejKAy TeM ohh iono.iHHK)T Apyr Apyra, xapaKTepH- 3ya cooTHomeHHe Meamy cocTaBAjnomHmh Pa6oTOcnoco6Hocm TpyuoBan aeaTejibHOcn. b oTjiaHne ot CnOpTHBHHX COpeBHOBEHHft BHIIOHHHeTCH, KaK npaBHJio, He npn mhkchmaxbBbix Harpy3Kax. IlpaKTHHecKoe aHaneHRe oueHKH Pa6oTOCnOC06HOCTH, HBJlHK3HleHCH B Ahhhom cjiynae noTeHUHaxbHofl xapaKTepHCTHKOfl, COCTOHT B TOM, HTO OHa OTpaataeT BejiHHHHy ipyHiaiHOHaAbHOro pe- 3ePBa, t. e. pa3Hmibi Meamy npeAexbHbi- MH B03M0JKH0CTHMH H paSoHHM ypOBHeM $H3HOJiorHiecKoro HanpHXteHHH. HaxHHiieM TaKOro peaepBa o6ecneiHBaioTcs KaHeCTBO H HaiieJKHOCTb HpH BHnOJIHeHHH pafioTbi, a TaKxce npeaynpeameHae ne- peyTOMJieHHH, Beaymero k pa3BHTHio npeanaTOJiorHH. nocuieanufi momsht hhot- Aa BKJiioHaroT b caMO noHHTHe pa6oTO- CJTOCOfiHOCTH (A. 0. HaBaKaTHKHH H B. B. KpbixcaHOBCKaH), xoth, crporo ro- BOpa, cxeAyer othochtb sto k Aoxe ee, AonycTHMofi aah peaAH3amni, t. e. k per- JiaMeHTHpyeMofi BexHHHHe pafionero HaIipHJKeHHH H COOTSeTCTBeHHO 3amHTH0ii 30HM, C03AaBaeM0ii (JjyHKIIHOHajIbHHM peaepBOM. Pa6oTocnoco6HOCTb He oieAyeT hachTHfpHHHpOBaTb C AfByMH ApyTHMH nOHHTH* HMH, 6AH3KHMH K HQA, HO AeJKamHMH B HHbix ofiaacTsx -- b cipepe couHajibHOSKOHOMHHeCKoft H B CCpepe npaBOBOfi. <rHmeaa Tpyaa r npo$eccKOHa:n>Hi>ie 3a6aieBaHH, 1983 DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service I Centers for Disease Control National Institute for Occupational Safety & Health Robert A, Taft Laboratories 4676 Columbia Parkway Cincinnati OH 45226 August 2, 1983 T. R. Torkelson, Sc.D. Health & Environmental Sciences 1803 Building Dow Chemical, U.S.A. Midland, Michigan 48640 Dear Dr. Torkelson: This is in response to your letter to Drs. Landrigan and Halperin, dated July 15, 1983, asking for comments on "The effect of methyl methacrylate and vinyl chloride on hypophyseal somatotropic function," by I.A. Makarov and K.I. Makarenko. The article suffers from a lack of information similar to that you noted in the Fedotova article. Since the criteria used to judge "chronic intoxication with MMA" and to diagnose "vinyl chloride disease" are not given, we cannot be sure what biases may exist in selection of the study group. Other potentially significant factors, such as age and obesity of the groups, are missing. No exposure levels are cited. Serial STH levels were studied in the exposed population, but not in the comparison group. There is, as the authors conclude on page 2, a significant difference in baseline STH levels between the control group and each of the exposed subgroups. I am not sufficiently familiar with STH response patterns to know whether parodoxical reactions in 10 subjects out of 78 constitutes a significant finding; in view of the other deficiencies in the reporting of the study, the point doesn't seem worth pursuing. The therapeutic effort for Patient E (transferring her away from MMA exposure), and the outcome of that effort (remission of symptoms), seem inconsistent with the proposed mechanism of action. Despite the failure to report methods and results completely, there appears to be something happening in the study group. We may hope that similar tests will be repeated with more stringent attention to methods and reporting. Sincerely yours. R&S 116904 Epidemiology Section I Industrywide Studies Branch Division of Surveillance, Hazard Evaluations and Field Studies PO Box No 54 Wilton Works Middlesbrough Cleveland TS6 8JA England Telephone Eston Grange (0642) 454144 Telex 587461 Cables, ICIWilton Middlesbrough Telex Nearest Airport -- Teesside 19 miles from Wilton 4 Dr T R Torkelson # Health & Environmental Science 1803 Building Dow Chemical Midland MICHIGAN 48640 USA c.c. Dr B Bennett, Hillhouse Works Your ref Our ref Tel ext 'i Imperial Chemical Industries PLC Petrochemicals and Plastics Division MEDICAL DEPARTMENT Oate Dear Ted APW/MH 6566 13 Oct 83 RUSSIAN PAPER ON THE EFFECT OF METHYL METHACRYLATE AND VINYL CHLORIDE ON HYPOPHYSEAL SOMATOTROPIC FUNCTION As promised, I enclose an assessment of this paper by the Consultant Physician at the Royal Liverpool Hospital, Yours sincerely A P WRIGHT Division Medical Officer & Registered in England No 218019 Registered Office Imperial Chemical Home Mlllbank London SW1P 3JF 1981 PETROCHEMICALS DIVISION 30 fio 0) CT> CO O tn R&S 116906 Castne^-Kellner Site PO Box No 9 Runcorn Cheshire WA7 4JE Telephone Runcorn (09285) 73434 icn Imperial Chemical Industries PLC Mond Division Dr 0 M J Wi11iarns HD MFOM BP Chemicals Limited Sully Penarth SOUTH GLAMORGAN CF6 2YU Your ref Our ref CEB/SJW Tel ext 2455 Date 3 Oct 83 Dear David RE: RUSSIAN PAPER ON THE EFFECT OF METHYL METHACRYLATE AND VINLY CHLORIDE ON HYPOPHYSEAL SOMATOTROPIC FUNCTION I asked Dr Brian Walker who is a Consultant Endocrinologist at the Royal Liverpool Hospital, to criticize this paper. I enclose the critique as requested, and hope that it will be of some help I will leave it up to you to circulate it as you see appropriate. Kindest regards. Yours sincerely DR C E BARON (Medical Officer) fl*G!ttrd in Enflln No. 2'#019 R*gi(*r*d Oftieo Import*! ChomicaJ Houio Mlllbanc SW1RUF LIVERPOOL HEALTH AUTHORITY ROYAL LIVERPOOL HOSPITAL Prescot Street, Liverpool L7 8XP Telephone: 051-709 0141 Your Ref: Our Ref: 28 September 1983 Dr C Baron ICI Mond Division P.0. Box 1013 The Heath RUNCORN WA7 4QP RAW/DC n telephoning please ask for R&S 116907 Dear Charles Thank you for allowing me to see the enclosed paper. I hope you will forgive me if I Bay I am not too impressed with it* I think this is because I am a little unhappy about the methodology. I note that only the basal level of growth hormone was estimated in the control group, and this was claimed to be 5.4 plus or minus 0.2 ng/ml. A single growth hormone estimate is notoriously inaccurate and, indeed, in most normal individuals under such circumstances growth hormone suppression would be such as to make the levels unmeasurable. One, therefore, wanders about the accuracy of all the results in the other groups studied. The second point is that the lack of response to hypoglycaemia in the two groups chosen is, again, difficult to evaluate, as the majority of each group were suffering from chronic neuro logical intoxication due to side-effects of MMA or FDC. In other words, we are trying to assess growth hormone responses in people who have already significant evidence of CNS toxicity* The authors also stress a paradoxical rise of growth hormone during a glucose tolerance test in some workers, but it is my impression that this might well occur in any group of normal people. I think the spontaneous improvement in growth hormone in an acromegalic is a well-known natural phenomenon, probably due to 1 of the benign eosinophilic adenoma, and to suggest that this was brought about by exposure to chemicals is stretching coincidence a bit too far. In summary, my chief objection is that I really do not believe the methodology. For instance, at the top of page 6, "We consider that a drop of the 3TH level below 2 ng/ml is a symptom of a pronounced toxic action on the nuclei of the hypothalamus." Such a drop is frequently found in normal individuals. With kindest regards. Yours sincerely ^-,r - B A WALKER Consultant Physician From G M Paddle To Dr B Bennett Works Medical Adviser Hillhouse Works Your ref Our ref GMP/EJ Tel ext 248 u C-' imperial Chemicals Industries PLC Central Medical Group Alderley Park, Macclesfield Cheshire. SK10 4TJ Telephone : Alderley Edge (0625) 582332 Telex : 669095/669388 j. Copies to Dr J Stafford Petrochemicals & Plastics Division, Welwyn Date 9 September 1983 f .:z W TV. PAPERS BT FEDOTOVA AND MAROROV As requested I have reviewed these two recent Russian papers for you. Fedotova we have encountered before when he reported an absence of ASL cases in a Russian VCM cohort. The patterns of mortality he describes are typical of industrial cohorts followed for a long period of time and suggest that the conduct of the study was adequate. The results of the analysis are given as ratios rather than observed and expected figures so that the numbers of cases of each diagnosis cannot be calculated. I would guess that the figures for the lymphatic and haemopoetic systems are.small and might be clusters unrelated to occupation. The stomach cancer excess is a priori more likely to be due to social class factors rather than occupation. The findings cannot be summarily dismissed, but as they do not fit the established VCM pattern the relationship with VCM should be considered fragile. r The results in the Makarov paper are such as to make sophisticated statistical analysis redundant. A logical progression in the measurements of STH has been demonstrated. 1 have no idea what it means or whether it matters. R&S 116908 -