Document KGrbzdE1XgMbLYnpO3DY9vor6

|Eredice*.ioa. t493, Geneva, smallpox eradland global cerSME/7E.21, Ge'i: Towards tbe 39 Mar 1980. World Health and ie. JOURNAL Of 'HYGIENE, EM O J. 0 iC^Rl IOLOCY and i muunoi-'oFrH&^'asC^dTs.aj-=TyJi i _ u i i> C *_ Cc H ' JAN 2'15982 Environmental Affairs V/t NEUROLOGICAL CHANGES IN VINYL CHLORIDE* EXPOSED WORKERS f V. STtBLOVA'. v. lanbl*. O. CXCMCAL', V. KELLEBOVA', V. BASKOVA', J. VlTOVCOV*!, L. SLAB' l) Department ol Neurology, Medical Faculty of Hygiene, Charles University, Prague 3) Outpatient Clinic of Occupational Health, District Centre of National Health, MSlnDc, Czechoslovakia Vinyl chloride (VCJ toxicity for the human organism Is not still fully clear. The occupational exposure to VC is linked with the development of liver hemangiosarcomas, or with other malignant processes of varying locality. Some authors diagnose changes in terms of scleroderma, universally are described roentgenologically detected lesions of Interpbalangeal Joints and zonal osteoly sis. They are described In association with Raynaud's syndrome (12, 10, 1, 4, 5 and others). Lange with his colleagues (12) describes anglologlcally detect able constriction of digital arteries, stenosis or partial occlusion of phalangeal blood vessels. Described are also various types of dysesthesia In fingers, parti cularly cold and numbness sensations. Also Byczkowska (3) reports frequent occurrence 'of finger paresthesia, whitening of fingers, but also of palms and soles, and other symptoms of peripheral vasomotor disorders. Neurological manifestations are described only sporadically. Splrtas and colleagues (18) emphasize particularly the narcotic action of VC at . higher peak exposure concentrations. This manifests Itself by vertigo, nausea and hea dache pains. Mentioned are also hand paresthesias (prlnckltng, formication). Langauer-Lewowicka (11) analyzes also the clinical symptoms In her group of 200 examinees who showed most frequently signs of cerebellar symptomato logy. She 'recorded frequent occurrence of headaches and sleep disorders, but also trigeminal neuralgia. Because of a lack of more detailed neurological studies among the VC-ex* posed persons, we conducted field investigations among the occupationally ex posed workers In a plant where there was six years before put Into operation a workshop with a considerable VC hazard. , For Distribution by CMA SPECIAL PROGRAMS DIVISION Ref. No.. Date___ 233 SL 068522 ales), age ;e time of .ions with roups acn the tenbeen freand some '.tegory of here they :tung end compres* lively low A more 0 and N3 atlon was S persons eadaches . The in* s Ipalpii in can ned to vi- 19.6 4.4 > To 2J* o!o 00.0 s of exThe sub* :hes and Table 2. Overview of subjective complaints in workers occupationally exposed to vi nyl chloride, relation ro the level of exposure Comp! lints Headache Sleep disorders GIT disorders Vertigo Fsvchic disrurbatiou Dysesthesia Palpitations Total number of examinees Total number | % More exposed number | % 46 15.7 ' 19 17.4 16 dad 7 6.4 :o 3 6.9 1.0 112 10.1 1.8 13 '6 5.5 9 3.1 7 6.4 14 4.8 5 4.6 393 100.0 109 100.0 Lest exposed number | % 37 14.7 9 4.9 9 4.9 I 0.S 7* 3.8 -* 1.1 9 4.9 184 100.0 gastrointestinal disorders, and furthermore, of dysesthesia of extremities. There was observed elso a certain correlation with the length of exposure (Table 3). In persons with the exposure time longer than 4 years, the Incidence of heada ches was double the Incidence in the group with a shorter time of exposed for more than 4 years. Sleep disorders, gastrointestinal complaints, vertigo and psychic disturbances were also more frequent in those with a longer time of ex- Table 3. Overview of subjective complaints in workers occupationally exposed to vinyl chloride, relation to the length of exposure Complaints Headache Sleep disorders GIT disorders Vertigo Psychic distnrbauoa Dvsesthesis Palpitations Total number of examinees Total number O/O' 46 15.7 16 5.S 20 6.9 3 1.0 13 4,5 9 3.1 14 4.8 293 100.0 Exposure longer than 4 years number ro 24 23.8 8 7.9 9 8.9 3 3.0 8 7.9 8 7.9 4 4.0 101 100.0 Exposure shorter than 4 years nujobcf O/o' 11.0 8 4.2 11 5.7 0 0.0 5 2.6 1 0.5 10 5J 192 100.0 posed workers is characterized In Table 4. The group of more exposed workers showed a significantly lower per cent of normal findings and a higher per cent of more severe findings than the group of less exposed workers- ' 'Graph 1 presents Incidence of the most frequent, objectively diagnosed, syndromes detected in exposed and control groups. The most'lrequent was the lesion of peripheral neurons, either motor or sensory, or both of them (15.8 %: :8.7%), Diagnosed were impairments of muscle tonus or trophlcity, reduction or loss of tendon and bone reflexes, abnormal sensitivity. Compared to controls. 235 y exposed iXpojrd O/e' 62.S 34.2 3.3 100.0 matology icrohyposesthesle. diagnosed In VC-exposed workers were predominantly episodic, In 5 cases com* bined with the diffuse abnormity. Three EEG recordings revealed only diffuse abnormities. Relatively frequent was also the presence of sleep waves [in 46.5 % of cases). In 16 "Hi of workers the sleep activity manifestations were of jarlson to a lesions, D-- atrsl VC- level of . lesions: 11.8 %). 5 % And rrelation rs of ex< *&) and erebellar 1 control rdlngs In the EEG lormliles Graph 2: Objectively diagnosed changes In VC-exposed workers in relation to the level of exposure. X-axis abjecdvely diagnosed changes: A-D see Graph 1. Biank column -- lower exposure levels, hatched column -- higher exposure levels. Y-axis -- % of the total number of exposed subjects. a higher degree of severity [2c to 3, according to Roth (13)). Significant dif ferences were observed also In the photostimulation reaction that was normal only in 40 % of cases. The most frequent was extension of photic driving to wards beta and theta waves [in 43.4 % of cases). The additionally conducted N5 and EOD (6, 7, 8, 9) questionnaire surveys were used to improve analysis of subjective complaints and to complement Graph 3: Objectively diagnosed changes in VC-exposed workers In relation to the length of exposure. X-axis -- objectively diagnosed changes: A-D see Graph 1. Blank column -- exposure shorter than 4 years, hatched column -- exposure longer than 4 years. Y-axis -- % of the total number of exposed subjects. 237 <ww>r**cr .-.-I i.-.-_ SL 068524 trails es (Aalled !^ive ot . chloride. oo 70.4 23.4 6* 0.0 6.2 100.0 1 by anamnolence frequent thermore, :1s pensoicies that :y. In the from the manges n: .aints, -mg the cticr, of rebellar tas and .5) and revlous cenzene mcidence ;:ene. We :me cases peripheral rare date and to our own experience these changes are frequently associated with Ray naud's syndrome and may presumably lead to even more severe consequencles In terms of stenosis or occlusion, as described by Lange (121. Peripheral nerve lesions diagnosed In our group of VC-exposed examinees oould be then explain ed by a direct neurotoxic action of VC, or as a consequence of hypoxia ac companying more severe vasomotor changes In the periphery. The narcotic action of VC can be either transitory. Inducing only reversible changes In tbe brain function, or persistent, causing more permanent, sometime Irreversible changes In the CNS, Slight functional changes manifest themsel ves in EEG recordings by waves typical for various stages of sleep, as con firmed In a relatively high per cent (46.5%) of cases In our group''(jf exami nees as well as In some of tbe examined subjects exposed to other organic solvents (19, 21, 22). Detection of episodic or diffuse EEG abnormalities is rather more serious and may be Indicative of chronic changes in mediobasal and/or cortical brain structures. In our group of examinees, tbe joint episodic and diffuse abnormality occurred in 15.6 % of workers. This frequency is In agree ment with the cited literature data as well os with our previous experience. This leads us to a conclusion that even VC, particularly at higher exposure con centrations, can produce neurotic changes In the above described brain structures. VC-induced pathophysiological changes are believed by some authors to manifest themselves by tbe central neurovegetative dysregulation, as e result of changed hypothalamus functions (2). This localization, presumed by these authors on the basis of their experimental studies, seems to be In agreement with our findings of EEG episodic abnormalities. We also believe that even FS reaction changes, recorded In our group of exposed workers, may be of importance in the-early diagnosis of VC-induced damage. Comparable FS reaction changes were also described by RouskovA (14) in persons exposed to other toxic agents. CONCLUSIONS 1) Exposure to VC may lead, besides to other changes described In tbe li terature, also to lesions of tbe nervous system. Tbe onset and development of these neurologic changes depend on the VC exposure level and on the length of exposure. 2) Some of the neurologic manifestations are caused by tbe narcotic ac tion of VC, such as certain subjective complaints and cerebellar and/or vestibu locerebellar syndrome. These symptoms can be transitory or persistent. 3) Among the Important manifestations that are characteristic for VC ac tion is, no doubt, the peripheral vasomotor symptomatology, sometimes in com bination with the Raynaud's syndrome described In the literature. These vaso motor changes in the periphery may further develop, leading consequently to 239 rvw; it JJ" - * ,* T*. rv> a pi# m *;*4" -- "\ \h-_ SL 068525 '* -"_r- ,.'. .-. ..vrJ,'-'i---.rff.-^-c'Ca..t* ~" --- ->r---'-11 ---i i-- '-- V'-* -vj-ji *i 's?! !-'.-"',-.i 1-^---------- it are the gejgtascular dis^^pvegetative lesions causnanisms. ) the assumed is). It occurs 22) and may :al structures i be ascribed 3ns accompa;tent changes accentuated >rkers at risk essary to enrkers. Of the both for preostimulation. nelly exposed ad of NS and nulauon. were jects. Average ^^pvegetative ^Brler and/or al seurovege* to depend on inently episo* oosed showed episodic EEG o changes tn pact on the system and Serai symptoinsequence of ie systematic on the as* lory. Supple* RESUME S t f b 1 o v 4, V,, Lambl V,, C h u m c h a I, 0., K e 11 e r o v a. V,, Piiko- V4, V., VItoveov4, 2 1 a b, L.; L'image nenrologiqne chex lea xujeti axposts au cblorore de vinyle 11 a 4t4 etudie d'une manure complexe l'lmage oeurologique chez 293 sujets ex poses eu chlorure de vinyle. Des troubles subjectifs ont ete analysts au plan dttaint a l'aide des anquetes EOD et NS. II a ete mis en evidence un effet neurotoxique slgni* flcatlf prodult par chlorure de vinyle qul depend de la quallt et de le quantlte de l'exposltlon subie. Les troubles subjectifs rencontres le plus souvanr: meux de titeta^ymptOmes ve* getatlfs et dysesthesie. Les donnees objectives temolgnent pour une affection du systeme vestlbulocerebelleux et pour celle du neurone peripberiquc et de I'innervation ptrlphtrlque vegetative. Le symptflmatologie ptrlphtrlque peut resulter de I'effet toxique direct prodult par chlorure de vinyle aussi bien que du mecanlsme d'hypoxie ayant lieu lors des cbengements vesomoteurs peripheries. Oes donnes issues de l'EEG temolgnent une activite de sommeil chez -16,3 % de sujets demontrent un effet sercotique du chlorure de vinyle. L'actlvlte episodique (chez 13,5%) associee parfois i I'enonvalie de diffusion pourralt s'expliquer par une attelnte des structures medlobasales, mtme liee aux changements du cortex. Les sujets exposes a l'lnfluence du chlorure de vinyle ne se soumettent, Jusqu'4 ce jour, aux examens systemsnques au plan neurologlque. II est ntcessaire de poursulvre, dans ce cas. une prophylaxle neurologlque etudlant l'image dinlque, les donnees is sues de l'EEG ou tnfime de l'EMG. 11 est utile d'employer les anquetes EOD et NS. Zl'SAMMENFASSUNG S t y b 1 o v 4, V., Iambi, V_ C h u m c h a 1. 0., K e 11 e r o v a, V., P a S k o * v 4, V., V11 o v c o v a, V., 21 a b, L.i Neurologisches Bild bei den dem Vlnyichlo- rid exponierten Arbeitenden Man beobachtete kompiexerweise das neurologiscbe Blld bel 293 Arbeitenden, die Vlnylchiorid expomert weren. Subjektive Schwierigkelten analysierte man eingebender mil Hllfe der EOD- und N 5-Fragebogen. Dabel bat roan else signlflkante neurotoxische Elnwlrkung von Vlnylchiorid nachgewlesen, die von der Intertsltat und Deuer der Exposition abhlnglg 1st. Die bautlgsten subjektlven Schwierigkelten waren Kopfschmerzen vegetative Symptome und Dysesthasle. Der objekttve Sefund zeugt von der Affektlon des Vestibular* zerebellarsystems, ferner von der Affektlon des peripheren Neurons und der peripheren vegetatlven Innervation. Die penphefe Symptomatologie kann man erkl&ren so* wohl als direkte Elnwlrkung von Vlnylchiorid, als euch den bypoxlschen Mechanlsmus bei peripheren vesomotorischen Ver&nderungen. In dem EEG-Befund stellte man bei 43,5 % Title der Gesamtheit die Scblafaktlvitat test, die die sarkotlsche Elnwlrkung von Vlnylchiorid dokumentiert. Die eplsodlsche Aktlvltat (bei 15,5 %] manchma! In Verblndung mlt Dlffusionsabnormltat kOnnte man durch AffBktlon von mediobasalen Strukturen, gegebenenfals" durch Kortexveranderun* gen erkliren. Die Vlnylchiorid exponierten Arbeitenden werden bisher systematlsch vom neurologischen Standpunkt nicht beobachtet. Die Veriasser halten die gezielte neurologiscbe is 241 * W\, -`fir - 4&C * iff*-- *-,v rti wvcr SL 068526 >7r ^>:v"`iTr : V- Tj' A' *->?* "sf'sifcr .?:! *rfil gyentuell p- und PaSkoidores ax 's expuesnediante 1 vioilcloades sub* s asi que ilocerebetiva pen:o directo irieos pe- ii el 46,5 acrividad sa pod-la ' camblas irolfigicarevencidn ualmente R., Me Michael, A. L, Gamble, J., Vao Ert, M.: Am. Iod. Hyg. Ass. J. 36, 1975, 10, pp. 779--789. -- 17. Stable?*, V.: Frac. 16k. VII, 1955. 5, pp. 260-263. - 16. Stablest, v.: Acta Unlv. Carol. Med. Suppl. 12, 1950, pp. 269--274. -- 19. StfblovA, V.: Cs. neural. 26, 1963, p. 399. -- 20. Stjblo- vi. V.: DIagnoxa a prevence v prtimyslove neurologlL Praha. SZdN, 1968. -- 23, StjbIotA, V,: Int. Arch. Occup. Environ. Hlth. 38, 1977, pp. 263--282. -- 22- Stable?*, V,, Holanovt, V.: Prac. 16k. 25, 1973, pp, 90-- 965 Received November 10, I960 V. Stfblovi, Dept. Neurology, Medical Faculty ol Hygiene. Charles University, 5rob4rova^50, 100 42 Praha 10, Czechoslovakia V-T*T*--^_7'3?F^`S=7'* '7- ' 7 ',, --. 1 *-W*W1.*-- . *~ .^s-icsr*21 i+ pfe 1 ft'faV'fc.M.1 4 .^ ***'* -T- London iarris, D. sd. J. 16, gaoer-Lexkowska, sup. 21, E-. Jube, krch. Ar12. Roth, hlediska IS57. -- ;med. 34, .xOTi, K.: ehroaicml orga16k. sb. Spinas, SrO '5Ba V|* "-S.VSA. ife** diAb'asa . *tCT ;*>*' yW /.V'V'.-f 1 243 r '^Vu *'T*>V-'r*--vV*?W-J*' ,'S SL 068527