Document kDKxV3E0v7xKz8N9ygJ7zB1oV

JRL 15522 ~~1FJC FumW V<l V* w ? 1J1 IHl Pnaicd Cfcai Imm * . S' I.; '* l-i. -.- . - v \j . , ' . : r I &(Lj- - MT .'j-.-.i r- mmxii o.xmMnMeo* HvfrflMM h 14 ;|| LIFESPAN ORAL TOXICITY STUDY OF VINYL CHLORIDE IN RATS* V. J. Finos, C. F. M. Henmuksen. A. I. Srenc. ' H. P. Til and B. J. Sht Institute ClVO--Toxitokw and Sumtion TSO. PO fax Jfttl, yUX) AJ. Zfist. The Netherlands iReteited A July ?WW) * * Abstract--A lifespan oral toxicity study of vinyl chloride monomer (VCMl vu carried out in Wistar rats, usinf five groups each of 60 80 males and 60 80 females. VCM Has administered by incorporating polyvinyl chloride (PVO ponder with a high VCM content into the diet or by gastric iniubation of a 10". VCM solution is soya-bean oil. The VCM doses tactual eipoaures) were 0 (control). 1-7. SO and 141 mgkg body weight day provided by diets containing PVC powder, and 300mg kg body weight given by stomach tube as a solution of VCM in oil on S days/wk. The death rate was higher in all VCM-treated groups than in the controls and increased with increasing VCM doses. The 14-1- and 30Omg kg treatments were associated with shortened blood-dolling times, slightly increased a-foetopro- tein levels in (he blood serum, liver enlargement and an increased haematopoietic activity m the spleen. A variety of neoplastic and non-oeoplastic treatment-related liver lesions was found at each of the VCM levels. The changes varied from swollen and irregularly-shaped mitochondria in hepatocytes to hepato cellular carcinomas and hepatic angiosarcomas. The tumour response of the bver appeared to shift from a predominance of angiosarcomas at the highest dose level tis a mixture of angiosarcomas and hepato cellular tumours at the intermediate Levds to the exclusive development of hepatocellular tumours at the lowest VCM level. Tumours attributable to VCM exposure and found at other sites included pulmonary angiosarcomas, estrahcpatic abdominal angiosarcomas and tumours of the Zymbal glands; these neo plasms occurred at VCM levels of 50 mg kg and above. In addition, there was some evidence that VCM exposure enhanced the development of abdominal mesotheliomas and of adenocarcinomas of the mam mary glands Thus, the prevent study showed that orally administered VCM is a carcinogen in rats, and that the "no-observcd-adverve-effect leveT in ran was lower than 1-7 mg kg body weight day under the rigorous conditions of continuous oral VCM exposure resulting from the release of VCM from PVC powder present in the gasiro-intestinal tract. ___ `u ^ . ,v ^->j-ll.*.; . &' M %*, INTRODUCTION Industrial exposure to vinyi chloride monomer (VCMl has been associated with disorders such as acro-osicolysis. non-malignani liver disease, angiosar coma and carcinoma of the liver, and tumours of the brain and lungs and of the lymphatic and haemato poietic systems IHaley. 1975; Hopkins. 1980; Monson. Peters A Johnson. 1974; Rawls. 1980; Thomes A Popper. 1975; Vale. Kipling A Walker. 1976; Wuwciler. Stringer. Wagoner. Jones, Falk A Carter, 19761. In addition, various types of tumours, such as hepatic and extrahcputic angiosarcomas, hepatocellu lar tumours, mammary-gland carcinomas, Zymbalgland tumours, nephroblastomas, brain tumours, pul monary adenomas and nasal olfactory carcinomas, as well as a series of non-neoptasiic lesions in several organs, have been found in a number of animal spe cies after prolonged exposure to atmospheres contain ing VCM at- sufficiently high concentrations (Basa laev. Vaan A Kptchetkov. 1972; Feron A Kroes. 1979; Lee. Bhandari. Winston. -House. Dixon A Woods. 1978; Maltoni A Lefemine. 1975; Suzuki, The study was sponsored by a group of co-operating European industrial concerns, including Verband Kimststoffemugende Industrie t.V. (FRGL Shed Nederland Chemie. Dutch State Mines. Akzo Zout Cheak Neder land B V. and Dow Chemical Europe SA. 1978; Torkdson. Oyen A Rowe, 1961; Williamson. 1976; Wineil, Holmberg A Kronevi, 1976k Residual VCM present in extruded polyvinyl chlor ide I PVC) has been shown to be liable to migrate into PVC-packcd foods and drinks (Daniels A Proctor, I97S: Fuchs, CawelL Albanus A Slorach, 1975; Pot ter, 1976; Randolph. 1973; Williams A Miles. 1975k There is still only a small amount of data on the oral toxicity of VCM. fn a 13-wk toxicity study, in which the monomer was dissolved in soya-bean oil and ad ministered to rats at levels of 0, 30, 100 or 300 mgkg body weight, once daily on 6da\s'wk. the no-effectlevel was conservatively placed at 30 mg/kg body weight but was probably higher since the effects at the higher doses were of doubtful toxicological signifi cance (Feron. Speck, Willems, van Battum A de Groot, 1975k From preliminary observations it appeared that a more practical method for chronic oral exposure of rats to VCM is the feeding of diets containing PVC powder with a high VCM content (Feron et at. 1975k Therefore, in the present lifespan study. PVC powder containing VCM was incorpor ated in the diet at levels to give planned daily intakes of I. 3 or tOmg VCMItg body weight. This method does not allow dietary VCM intakes much higher than 10 mg/kg body weight,day. a dose that is. how ever. very high in comparison with a recent estimate of the maximum likely oral daily intake by man, ij. 00017 jig VCM/kg body weight day or 0-1 pg VCM/ III Hi 117 **?V-I-tTif, i r'r. ~ ;V. fo- ,1 * '.'fc'. Vy- i e f"4; r. - I pox Eradication. Jo. 493, Geneve, smallpox eradland global car- SME/78.21, Cm'is Towards tht 19 May 1980. World Heelth sad fall* -g" ^ f" ~ 4\fsU 0yj " pM I V O'^TOlcnt. KM0KK1OU8T. tCO.IOl*Gt and iMsoHoiooi a. mat, xa. j, m>2u F***./*/fc / +, % v>_ , . ^H| S- + - ?> -/ J PA JAN 21 ',982 /=?"/ ECr NEUROLOGICAL CHANGES IN VINYL CHL<5BSU8-jggo EXPOSED WORKERS medical departMj\JT V. STfBfcOVA', V. UMIL>, O. CXOUCAt*. V. KtUCKOVAt, v. faSkova*. r. vitovcova*. l. it a a* i) Department of Neurology, Medical Faculty of Hygiene, Charles University, Prague 21 Outpatient Clinic of Occupational Health, District Centre of National Health, Mllnflc, Czechoslovakia Vinyl chloride (VC) toxicity for the human organism is not stlU fully clear. The occupational exposure to VC is linked with the development of liver hemangloaarcomas, or with other malignant processes of varying locality. Some authors diagnose changes in terms of scleroderma, universally are described roentgenologlcally detected lesions of lnterphalangeal joints and zonal osteoly sis. They are described in association with Raynaud's syndrome (12, 10, 1, 1, 5 end others). Lange with his colleagues (12) describes angiologically detect able constriction of digital arteries, stenosis or partial occlusion of phalangeal blood vassals. Described ere also various types of dysesthesia in fingers, parti cularly cold and numbness sensations. Also Byczkowska (31 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. Spirtas and colleagues (19) 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 (prlnckllng. formication). Langauer-Lewowlcka (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, tut also trigeminal neuralgia. Because of a lack of more detailed neurological studies among the VC-exposed 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 a - ro aS MATERIAL AND METHODS Th* group of examinees consisted of 293 workers (283 males and 30 females), age 18--53 years, mean as* 32.8 years. Of these 78 H were below 40. The average time of exposure was 24 years (range from 2 month* to 8 years). After consultations with plant'physician and plant toxicologist the group was divided into two subgroups ac- . eordlng to the level of exposure. The subgroup of high-risk workers, la which the ten- iMtjKi ti tatively established maximum allowable concentration of 10 nig. had been fre- ff* ~ quently and sometimes highly exceeded, involved polymerization worker^. and some maintenance workers (e total of 109 persons). The subgroup of lower-risk category of /'^'Vorkei* included those engaged In drying and bagging operations, but even here they were sometimes exposed to high peak exposure concentrations during cleaning and sampling operations, and those from the other plant workshops -- combustion, compres sors, cracking, chlorination, regeneration -- where the exposure risk was relatively low (a total of 184 persons). All the worker* were examined ncurologically, some of them repeatedly, a more detailed analysis of subjective complaints was performed on the basis of EOD and NS questionnaire surveys. Electroencepbalograpbic examination with photostimulation was made Is 232 parsons (25S recordings). The group of controls consisted of 48 persons without exposure to toxic substances. RESULTS An' overview of subjective complaints Is presented in Table X. Headaches occur frequently, but they are less frequent than In the control group. The In cidence of gastrointestinal disorders and other neurovegetatlve disorders (palpi tations, retrosternal pressure sensations) are significantly higher than In con trols. Psychic disturbances were observed only in those exposed. Table 1. Overview of subjective complaints in workers occupationally axposad to vi nyl chloride, Id a comparison with controls \ VC -- exposed BOttbCf % Controls number o/o/ Sleep disorders GIT disorder* Vertigo Payable disturbataos Dyietthasii Palpitations Tow number of 46 16 20 3 IS 9 14 293 13.7 S3 6.9 1.0 43 3.1 4.8 100.0 9 19.6 2 4.4 1 13 1 24 0 0.0 1 24 0 0.0 46 ^ 100.0 Significant differences were observed between the two subgroups of ex posed workers divided according to the level of exposure (Table 2). The sub group of more exposed worker* showed a higher incldencg-of headaches and 234 Table 2. Overview Complain: A Headache Sleep disorders GlT disorders Vertigo Psycaie disturbatioi Dysesthesia Palpitations Total somber of ex; gastrointestinal was observed al: In persons with ches was double more than 4 ye< psychic disturba: table 3. Overrtet n <_n cfOn Complaint Headache Sleep disorders GIT disorders Verdfo Psychic disturbatioi Dysesthesia Palpitations Total namber of ex. posed workers li showed a signlf cent of more set Graph 1 pre syndromes detec lesion of periphe : 8.7 %). Diagnoi or loss of tendoc alas), as* Urns of ions with roups sc* i the tea* bsa !rcmd some tegory of here they aiog sod com presivdy law . A ooru 3 and N5 ition was 3 parsons adache* The in- s (palplin con- ad to vi- 19.6 4.6 2.2 2J 0.0 2.2 o!o )0.O j of exThe subties and Table 2. Overview of subjective complaints lo workers occupationally exposed to vi nyl chloride, relation to the level of exposure Complaints Headache Sleep disorder* GXt disorders Vertigo Psychic disturbatioa Dysesthesia Palpitations Total vtmbvr of examinees Total Somber /o 46 15.7 16 5.5 20 6.9 3 1.0 13 4.5 9 3.1 14 4.3 293 100.0 Mare exposed somber % * 19 1 11 2 6 7 5 109 17.4 6.4 10.1 l.a 5-5 6.4 4.6 100.0 Less exposed mimtm % 27 14.7 9 4.9 9 4.9 1 0.3 7 3.3 n -o' 1.1 9 4.9 184 100.0 gastrointestinal disorders, and furthermore, of dysesthesia of extremities. There wss observed also a certain correlation with the length of exposure (Table 3). In persons with the exposure time longer than 4 years, the incidence o! heada ches was double the incidence In the group with a shorter time of exposed for more then 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 la workers occupationally exposed to vinyl chloride, relation to the length of axposure Complaiats Headache Sleep disorders GIT disorders Vertigo Psychic disturbstioa Dysesthesia Palpitation# Total Dumber of examinees Total number % 46 15.7 16 5.5 20 6.9 3 1.0 13 4.5 9 3.1 14 4.3 293 100.0 Exposure longer than 4 years number % 24 23.8 8 7.9 9 8.9 3 3.0 3 7.9 8 1.9 4 4.0 101 100.0 Exposure shorter than 4t years dember % 22 11.0 8 4.2 11 5.7 0 0.0 5 2.6 1 0.5 10 5.2 192 100.0 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 par 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'frequent was the lesion of peripheral neurons, either motor or sensory, or both of them (10J H; : S.7 %). Diagnosed were impairments of muscle tonus or trophlclty, reduction or loss of tendon and bone reflexes, abnormal sensitivity. Compared to controls. 235 rr* m m m #2 ?'?C ;s*i *Sj; -^*4 S3 ??* :* ? A'? Table 4. Severity of objectively diagnosed changes in workers occupationally exposed to vlnyi chloride in relation to the level o( exposure Severity of changes Normal Light chances Manifest changes Total number of examinee* Total % 145 S7.0 112 38.0 16 5.0 293 100.0 More exposed number % 50 46.0 49 45.0 10 9.0 109 100.0 Lee* expend Bomber % 115 V 184 6Z5 34.2 3J 100.0 the group of exposed workers showed also more frequently the symptomatology of peripheral neurovegetative disorders 112 44:4.4%), specifically acrohypothermy, acrohyperhidrosls or whitening of fingers, associated with dysesthesia. diagnosed tn VC-e blned with the di abnormities. Rela 46.5 % of cases). Graph l: Objectively diagnosed changes in VC-exposed workers in a comparison to controls. X-axis -- objectively diagnosed changes: K -- peripheral neuron lesions, B -- parlpheral neurovegetative symptomatology. C -- cerebellar symptomatology. D -- vestibular symptomatology. T -- extra pyramidal symptomatology, G -- disperse central symptomatology. Blank column -- group of controls, hatched column -- group of VC' exposed. Y-&xu -- % of examinees Graph 2 shows objectively diagnosed symptoms In relation, to the level of exposure. A marked difference Is in the incidence of peripheral neuron lesions: more exposed workers are affected more than twice as often (25.8 % : 11.8 %]. Celebellar and vestibular syndrome is also more frequent (10%: 7.6% and 6.4%: 3.3%, respectively). There are also certain Indications of a correlation with the length of exposure, see Graph 3: those with more than 4 years of ex posure have more frequently peripheral neuron lesions <22.8 %: 13.8 %) and cerebellar impairments (13.9 %: 5.7 %). Frequency of the vestibulocerebellar syndrome is also higher (5 % : 0.5 %) in these persons. The results of EEG examinations of exposed and 81 non*exposed control workers are compared In Table 5. The per cent of abnormal EEG recordings In the group of exposed workers is higher than In the control group; the EEG abnormities detected in the controls were always least severe. Abnormities 236 . Graph 2: Objective! of exposure. X-axts lower exposure lev: a higher degree < ferences were ob: only In 40 % of i wards beta and th The additions were used to 1m Grepb 3: Objective! of exposure. X-ex column -- expose than 4 y ly -exposed 'actMMd II O/ 62.5 M.2 3J 100.0 ontology icrohyposesthesia. diagnosed In VC-exposed workers were predominantly episodic, in 5 cases com* blned with the diffuse abnormity. Three EEG recordings revealed only diffuse abnormities. Relatively frequent was also the presence of sleep waves (in 46.5 % of casesj. In 16 % of workers the sleep activity manifestations were of jartaon to Q ItSU>as. iogy, O -- st central up of VC* level of i lesions: : 1L8 %}. .3 % and rrelatlon rs of z> H) and erebellar 1 control rdlngs In the EZG lormitles Graph 2i Objectively diagnosed changes in VC-exposed workers in relation to the level of exposure. X-axls ablectlvely diagnosed changes: A-D see Graph 1. Blank 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 paly 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 EOO (6, 7, 8, 9] questionnaire surveys were used to improve analysis of subjective complaints and to complement Graph 3: Objectively diagnosed changes is VC-exposed workers is relation to the length of exposure. X-axls -- objectively diagnosed changes: A-D see Grapb 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 '^TTTW A. (f. -s!???ea r;-- j.r.; y.-it - ttL x . 'i anamnestic data. The questionnaire N5 examines superficial personal traits as well as certain clinical symptomatology, particularly neorovegetative syndro me, neurasthenic, depressive and anxiety-phobic symptoms, and the so-called toxic syndrome. Data provided by this type of questionnaire were suggestive of Table S. Seventy of EEG changes is workers occupationally exposed to vinyl chloride, la a comparison to controls __ EEC change* Normal Sospeet Abnormal Total slight medium total Exposed number % 148 63.8 48 20.7 30 12.0 6 2.6 36 15.S 233 100.0 Coatxob number % 57 70.4 19 23.4 5 64 0 0.0 s 64 81 100.0 a higher frequency of sleep disorders (36%'} than originally revealed by ana mnestic data, highly frequent (5 % level of significance) was also somnolence (76 %), which had not been also indicated in personal histories. More frequent were also feelings of bad performance, fear of loosing life or health. Furthermore, the frequency of hyperhidrosls was also very high (73 %). The Eyseneck perso nality questionnaire examines neuroticism. It reveals subjective tendencies that are evaluated by the examinee and confronted with the objective reality. In the examined group there were not detected any significant deviations from the norm; increased neuroticism could not be demonstrated. DISCUSSION Clinical examination of VC-exposed workers revealed significant changes predominantly in neurologic symptomatology. Some of the subjective complaints, such as headaches, vertigo, sleep disorders or increased sleepiness during the day, as revealed by questionnaire N5, are suggestive of the narcotic action of VC, similarly as the occurrence of the cerebellar and/or vestibulocerebellar symptomatology. These changes have been, already described by Spirtas and colleagues (16], Langauer-Lewowicka (11), but also by Schwartzovd (IS) and others. This characteristic symptomatology was also described in our previous studies concerned with the occupational exposure to trichloroethylene, benzene and other organic solvents (17, 13, 20). Here we also observed a high incidence of dysesthesia after exposures to some solvents, particularly to benzene. We escribed it either to peripheral vasomotor changes, or -- at least in some cases -- to initial phases of polyneuropathy. In cast of VC the presence of peripheral vasomotor changes is evidently very significant: according to literature data 238 ^4. and to our own t naud's syndrome in terms of steno lesions diagnosed ed by a direct n coapenylng more The narcotic changes is the bt irreversible chan ves In EEG reco firmed in a relat nees as well as solvents (19, 21,: more serious ant cortical brain st diffuse abnormal ment with the c This leads us to Generations, can structures. VC-lnduced C manifest thsmse: XI of changed hype authors on the t cn cn with our finding; fsj OO We also bel exposed worker: damage. Comp&r in persons expos 1) Exposure teracure, also to these neurologic of exposure. 2) Some of Cion of VC, such locerebellar syn 3) Among t Uon Is, no doub bination with tl motor changes traits as syndroso-celled estiva of chloride. to.* 23.* 6.2 0.0 6^ 100.0 l by ana* zmolence frequent hermore. :fc perso.eies that y. In the from the changes mplaints, urlng the action of -erebellar irtas and (15) and previous , benzene incidence zeae. We )=e cases eripherai 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 (12). Peripheral nerve lesions diagnosed in our group of VC-exposed examinees oould be then explain* ad 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 la the brain function, or persistent, causing more permanent, sometime irreversible changes In the CNS. Slight functional changes manifest themsel ves in ERG recordings by waves typical for various sages of sleep, as con firmed in a relatively high per cent (46.5%) of cases in our group"^ exami nees as wall as in some of the 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, the joint episodic and diffuse abnormality occurred in 15.S % of workers. This frequency is la agree ment with the cited literature data as well as 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-lnduced pathophysiological changes are believed by some authors to manifest themselves by the central neurovegetatlve dysregulatlon, as a 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 Rouskovd (14) in persons exposed to other toxic agents. ' CONCLUSIONS 1) Exposure to VC may lead, besides to other changes described In the li terature, also to lesions of Che nervous system. The onset and development of these neurologic changes depend on the VC exposure level and on the length ot exposure. 2) Some of the neurologic manifestations are caused by the 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 to ***.,>*** .y--*5*::-' :tv> -w : -1 mors ssvsrs lesions of psnpberal blood vessels. Equally important are the ge nera] neurovegetatlve manifestations (gastrointestinal and cardiovascular dis orders, hyperhldrosls, etc.) that might result from the central neurovegetatlve dysregulatlon. Important are also symptoms of peripheral neuron lesions caus ed by a direct neurotoxic action of VC or by hypoxia-related mechanisms. 4) Episodic abnormality tn EEG recordings seems to agree with the assumed involvement of hypothalamic structures (Basalajev and colleagues). It occurs even at exposure to the other types of organic solvents (IS, 19, 21^J2) and may be Indicative of a more diffuse affliction of mediobasal and cortical structures of the brain. Less severe manifestations of EEG sleep activity can be ascribed to the necrotic action of VC, more pronounced sleep manifestations accompa nied with abnormal EEG changes may be suggestive of more persistent changes In the CNS. 5) Neurological changes have not been so far sufficiently accentuated In the professional literature and, therefore, the monitoring of workers at risk is not conducted systematically and by suitable methods. It is necessary to en sure a neurological prevention in these occupationally exposed workers. Of the supplementary methods of examination there are recommendable, both for pre vention and research purposes, to use EEG examination with pbotostimulatlon, questionnaires N5 and EOD, and electromyographic examination. SUMMARY Neurological examinations were conducted in 293 workers occupationally exposed to vinyl chloride. Subjective complaints were evaluated on the background of NS and EOD questlonnare survey analysts, EEC examinations, including pbotostimulatlon. were performed in 232 persons. The control group comprised. 46 nonexpoced subjects. Average time of exposure was 2.8 yean, the longest time of exposure was B years. Among the most frequent subjective complaints ware headache, neurovegetatlve disorders and dysesthesias, among objective findings dominated cerebellar and/or vestibulocerebellar syndrome, lesions of peripherel neurons and peripheral neurovege tatlve symptomatology. Subjective and objective symptoms ware found to depend on the exposure level and the time of exposure. EEG examinations confirmed in 15.5 % of cases abnormities, predominantly episo dic, sometlnmes combined with the diffuse abnormality. 46.5 % of the exposed shewed presence of sleep activity as a consequence of VC narcotic action. The episodic EEG activity could be ascribed to lesions of mediobasal structures, or even to changes in brain cortex. Our data bate confirmed that vinyl clorlde has e considerable impact on the human nervous system. Most frequent are lesions at vestibulocerebellar system and vigUlty disorders due to VC narcotic action. Frequent occurrence of peripheral sympto matology can be explained by a direct neurotaxlc action of VC. or as a coosequenca of hypoxia caused by peripheral vasomotor changes. As a rule, regular check-ups of VC-txpased workers do not lnelude systematic neurological examinations. The systematic neurologic prevention, based on the as sessment of clinical. EEG and/or EMG examinations, should become obligatory. Supple mentary use of NS and EOD questionnaire surveys^* highly .gtvlsable. 240 Stfblov* v 4, V- V f t o V efaiorure de via U a 6t at- posts au chlcn & 1'alde des am flcatif produii 1`exposition sub Les trouble gfttattfs et dyst t4me vestibule ptrlphtrlque w xique direct pi ayant lieu lors Des donnti sujets dtmontr (chez 15,5%) attaints des st Las sujets jour, aux exam C 33 dans ce cas, i sues de 1*EEG CO o S t J b1 ov vt, V,, Vlt rid expoaiertei Men beob; Vlnylcblorld e mlt Hilfe der Elnwlrkung v Exposition abt Die hiufti tome usd Dy: zerebellarsysti ran vegetatm wohl els dire: bei perlpherer In dam EEC test, die die Aktlvltlt (be! durch Alfektl gen erkl&rao. Ole Vinyl gisehen Stani it are the geovascular dismrovegetatlve lesions caushanisms. i the assumed 2s). It occurs 22) and may cal structures n be ascribed cos accompastent changes accentuated irkers at risk essary to enrkers. Of the both tor pre:ostimulation. maily exposed ad of NS and aulatioa. were ijects. Average rs. surovegetartve oellar and/or al neurovegtto depend on inantly apisoposad showed episodic EG :o changes la ipact oa the : system and beral syspto* msequence of :e systematic 1 on the asstory. Supple* RESUME Stfblovi, V., Limbi, V., Cbumebat, O., K a 11 e r o v 4. V., p a $ k a v a, V11 o v c o v *, J., 21 a b, L.; Linage neorologlqae ehaz tee snjets expos4s am ehlonre da vinyl* 11 a 4t4 itudli d*unt maniire complex* I'lmaga aeuroiogique chaz 293 au]ets ex pose* au chlorure da vinyl*. Das troubles eubjectlfs one 4ti analysis au plan detain* 4 Taida des anquates EGO at NS. II a 4t4 mis en Evidence un effet neurotoxique signiflcatif produtt par chlorure de vinyte qui dtpend de la quallti et de la quantltd da rezposttion sobie. Lee troubles subjectlfs rencotttrte la plus souvant: maux da tita^yraptOmes vigdtadfs at dysasthdsle. Les dosndes objectives tamoignent pour un* ejection du sys tem* vestlbulociribelleux et pour ceile du neurone p4rlph4riqu* et d* rtnnervatton p4rlph4rique vigitaavt. La syaptdmatologle pirlpbirique peut rteulter de I'ettet toxlque direct prodult par chlorure de vinyte aussi bias qua du micanlsme d'bypoxie ayant lieu lore des changeaents vasotnotaurs piripbdriquas. Des donn4s Issues de I'EEG t4moignant une eettvit4 de sommell Chez 44,5 H de sujats diraontrant un a!!tt nareotiqut du chlorure de vinyle. L'activltd 4pisodique (chez 15,5%] assoei4e partois t I'anomakia da diffusion pourrait s'expllquar par una attelnta des structures midlobasalas. mime Hie aux changements du cortex. Les su]ets expos4s i ^influence du chlorure de vinyle oe se soumettent, Jusqu'A ce jour, aux axamans systimadques au plan neurologique. U est o4cessalr* da poursuivre, dans ce cas. une prophylaxle nsurologique itudiaot Linage cliaique, les donates is sues de 1'ESG ou mime de 1'EMG. II est utile d'employer les anquites EOO at NS. ZUSAMMENFASSUNS Stfblovi, V,, Limbi, V.. Chuoehal. 0.. K e 11 e r o v 4, V.. Palkov4, V., Vltovcovl. V.. 21 ab. L.: Neurologtsches BUd bei ten dam Vioylchio* rid expoaiertea Arbaitaadea Man beobachtete kompiexerweisa das neuroiogisebt Slid bei 293 Arbettenden. dia Vlnylchlorid expooiert waren. Subjektive Schwterigkaitta analysiartt man eingehander mlt Wife der EOD- und N 5-Fragebogen. Dabel bat man aiae signUUcanta naurotoxischa Elnwirkung von Vlnylchlorid oachgawiasen, die voa der Intensitit und Dautr der Exposition abbingig 1st. D'i* blullgstan subjektiven Schwierigkeiten waren Kopfschmerzen vegetauva Symptoaa und Dysesth&st*. Der objektiv* Befund zeugt von der Affektioa des Vestibularzerebellarsystems, ftrnar von der Affektioo des pripher*n Neurons und der paripheran vegetattveo Innervation. Dia periphere Symptomatologle kann man erkltr*n sowohl ais direkt* Elnwirkung von Vlnylchlorid, als auch den hypoxlscben Mechanismus bei perlpberen vasomotorischen Verinderungaa. In dam EEG-Befuad stellt* man hai 46.5 % Tiela der Gesemtbeit die Scblefektivittt fast, die die narkotischa Elnwirkung voa Vlaylchlorid dokumentlert. Die eplsodlscha Aktivttit (bei 15,5%] mancbmel in Verbindung mlt Dlffus.ionsabnormitgt kflnntt man durch AfMrtlon von medlobasaien Strukturec, gegebeoeafair durch Kortexverindarungtn erkliren. Die Vlnylchlorid exponierten Arbettenden werden bisher systematiscb vom neurologischen Standpunkt nicht beobaebtet. Die Verfasser balten dia gtzielte seuroiogische vv 241 Ul. -L*.. 1 w zszr.r :snc>. Vorbeuguag is Verbindung mil Btobachtung des kiiaischen Blldes, des EEG- eventual! such des EMG-Befundes for notwendig. Saar geeigoet 1st die Anweodung der 00* und N S-Fragebogeo. RESUMEN IL. Me Michael. A. U, M.: Am. led. Hvg. A pp. 779--789. -- 17. 14k. VII, 1955, 5, P Stfbiovd, Vj Acta Uni' 12, 1950, pp. 269--274. Cs. neuroL 20, 1953, p S t J b l o v 4, V,, LambI, V.. ChumchaU 0., K 11 r o v 4, V., P a f k o v 4, V., V11 o v c o v 4, V., 2 l a b, . L.: El cuadro aearol6gico so tribe ladarja paestot el viaiicloruro Received Kovambc Se ha examined globalmente ei cuadro aturolOglco en 293 trabajadore* expuee* tos al vinilcloruro. Las dificultades subjetivos sa ias aaaiizd deralladamente mediant# los cuestlooarios SOO y N 5. Se mostrd al resultado neurotOxico marcado dal vinilclo* ruro, el qua dependla da la altura y duration da la exposicida. Las dificultades sub* jetlvas a4s fracuentes eran los dolores da la cabeza. los sfntomas vagatatlvos ast qua la dlsestesia. El hallaxgo objatlvo muastra la afeetacldn dal slstema vastlbulocarebe* lar, asl qua la da la neurone vagetatlva perifdrtea y da a iaarvaclOa vegetative part* fdrlca. La slntomatologla perlfdrica la puadt expllcar tanto por al alacto tOxico dlrecto 3el vinilcloruro, como por el macanismo hipOxlco con los cam bios vasomotOrlcos pa* ritancos. Sa ballO an ballazgos electroencafalogrdficos una actividad dal suefio en el 45,5 !i p. c. dal coa]unto. lo qua prueba al resultado narcOtico dal vinilcloruro. La actividad eplzbdlca (en el 15,5 p. c.J, a veces en la comblnaciO^ con la anortnidad dlfusa podrla se expllcar por afactaciOn de las structures mediobasales, eventualmente por eambios da la epidermis. Los trabajadore* expuestos a! vinilcloruro no son atln axamlnados neuroldgica- manta da manera tlstemAtica. Hace falta qua se haya reallzado naurolOgtca pravenciOn 7D ancamlcala induso al cuadro cUnlco, al ballazgo electroencefalogrittco, tventualmanta el alectroraiogrdfieo. Se recomianda user los cuestionarios 10 y N 5. oLtvtnJj REFERENCES 1. Angnlescn, T~, Otoio, m., Dobroaesca, E-: Mad. Int. 4, 1969, pp. 473--480. -- 2. Besalajee, A. V., Vazin, A. N., Kocetkov, A. C.: Gig. truda 2, 1972. pp. 24--27. -- 3. Byexkowska, Z., at aL: Pol. tyg. lekar. 29, 1974. 26, pp. 1461--1464. -- 4. Dianna, B. O., Warren, A-, WhiUhoue. W. M.: Arch. Environ. Hlth. 22, 1971, 1, pp. 01--73. -- S. Dodson. V. N., Bertram, D., Dlnman, B. D., Wbitabooae, W. M.: Arch. Environ. ,Hlth. 22, 1971, 1, pp. 83--91. -- 8. Engels* bub Cs. psycbol. 3, 1960, pp. 322-- 337. -- 7. EngaUmaaa, F., Drdkovd, S.: Cs. psychol. 4, 1364, pp. 340--346. -- 8. Engels* mina, F.. DrdkovS, S.: ACtiv. nerv. sup. 2, 1959, pp. 108--118. -- 9. Eysenck, H. Eysenck, S. G. B.: Manual of tbs Eysenck Personality Inventory. Univ. of London Press, London 24. 1964. -- 10. Harris, D. K.. Adams, W. G. M.: Brit. Mad. J. 15. 1967, pp. 712--714. -- 11. Ungaoar*Le* wowfeka, iL, Korzbanar, H., Byexkowska, Z.. Wacka-Marek, T.: Acttv. narv. sup. 21, 1974, 4, pp. 290. -- 12. Lange, C. JahB, S., Slain, G., Veitmen, C.: lot. Arch. Ar* t-eitsmedl 32. 1974, pp. 1--32. -- 13. Roth. B.: Narkolepsia a hypersomnia Z hladiska fysiologie spiaku. Praha, SZdN, 1957. -- 14. Rooskov4, Vu IoL ArcK, Arbaltsmad. 34, 1975, pp. 263--299. -- 15. Schwartzoed, JL: Nturologitki a EEC n41zy u chronic* kfch prOmyslovJch oirav nAkterfrai organickfmt razpouStSdly. Plzeftskp 16k. sb. Suppl. 25. 1970, pp. 5--68. -- 16. Spirtas. 242 eventual! EDO- und Palkodora* tx- s expues* mediants ; vlnllclo* adas sub< s asl qua ilocerebeliva part* o dlrecto ricos pe- n el 46,5 acclvjdad sa podrla cambtos icoldglea* evanciOa uaimenta R., We Michael, A. L, Gamble, J., Van Eat, iCl Am. Isd. Hyg. Ass. I. 36, 1975, 10. pp. 770--769. -- 17. StablerA, V.: Prac. 16k. VII. 1955* 5, pp. 290--263. - 14. Stybiovt, V_` Acta Dote. Carol. Mad. SuppL 12, I960, pp. 269--274. -- 19. Stfblovg, V.; Cs. neutcL 26, 1963, p. 399. -- 20. Stjblo* *4, V~ Diagaoza a prevence v pr&myslov* aeurologlL Praha, SZsLN, 1966. -- 2L Stjblovi, iat Arch. Occup. Environ. Kith. 38, 1977, pp. 263--262. -- 22. Stfblavi, V., Rolanord, PraC. 16k. 25, 1973, pp. 90-- 96* Received November 10,1960 V. SrfblovA, Dept. Neurology, Medical Faculty of Hygiene. Charles University, Srob4rova^50, 100 42 Praha 10, Czechoslovakia London (arris, D. f. 19, ;eaer-La ikowstca, sup. 21, E* Juba. ,rch. Ar13. Roth, hladiska 1937. -- mad. 34. zov4. K.: chronic* ml orge16k. sb. Spirtas. 4449 Aust. N.L J. Med., II, No. 3, 198?, p. 290-2 ISOPHORONE DIISOCYANATE RESPIRATORY DISEASE (IPDI) C.VV. C/arke; P.M. A/dons INDUCED A 50-yr old mol* spray pointer developed severe asthma following exposure to point containing IPDI. 4452 Arch. Dermatol,, 117, No. 8, Aug. J987, p. 452-3 OCCUPATIONAL HISTORY AND ANGIOSARCOMA (LETTER) D.F. flub/rt Occupational disease; viny chloride/adverse offsets. URL 15534 J 4450 8rit. J. Dermatol., 105, fSupp/. 21), 1981, p. 19-2? VINYL CHLORIDE DISORDER A.f. Wo/lt*p A review on diseases caused by occupational exposure to vinyl chloride oir pollution. 9 rtf*. 4453 Mutat. Res., 83, No 2 1981, p. 271-89 IN VIVO AND IN VITRO ETHYLENE OXIDE EX POSURE OF HUMAN LYMPHOCYTES ASSESSED BY CHEMICAL STIMULATION OF UNSHEDULED DNA SYNTHESIS R.W. PerOf B. Widegrmn, t ai. Z 7 4451 Mutat. Re*., 83, No 1, 1981, p. 137-44 4454 TVotoiogy, 23, No. 3, 7981, p. 317-323 CHROMOSOMAL ANALYSIS IN VINYL CHLORIDE TERATOGENIC EFFECTS OF ALIPHATIC NITRILES EXPOSED WORKERS: COMPARISON OF THE STAN C.C WMitf V.H. Fernv R.F. Smith DARD TECHNIQUE WITH THE SISTER-CHROMATID Acrylonitrile,- Animal; Proprionitrile. EXCHANGE TECHNIQUE D. Anderson; C.R. Richardson- et al. A group of workers occupationally exposed to vinyl chloride and controls were exomined for the presence of chromosomal aberrations or sisterchromatid exchanges in their peripheral lymphocytes. These people comprised a 2nd sampling from a group of exposed workers and controls first exomined 18 months earlier. The vinyl chloride exposed workers showed levels of chromosomal aberrations elevated above those of the controls, but there was only a slight increase in sister chromatid exchanges. Sister-chromatid exchanges (5CEs) were -also examined from in vitro cultures of lymphocytes exposed, to vinyl chloride, both with and without metabolic activation. There was no increase in SCEs in vitro without metabolic ac 4455 tivation, but there was a marked increase with metabolic ac Teratology, 23, No. 3, 1981, p. 325-33 tivation and this increase was shown to be independent of cell-cycle phase. The small increases of SCEs in workers were not due to the inability of vinyl chloride to induce SCEs in human lymphocytes but were probably because of low ex MORPHOGENESIS OF AXIAL SKELETAL (DYSTRAPH1C) DISORDERS INDUCED BY ALIPHATIC NITRILES C.C. Wil/hife; M. Monn-Podii/o; V.H. Ferm; R.P. Smith posures and SCE levels could have returned to normal Acrylonitrile; Animal; Proprionitrile. relatively quickly after exposure. 15 xM. 'tvJxK, KU*. T.iUI \ wu QlSuA C* TABLE I Summary of the Bladder Tumor Incidence Numerators for the Exposed Population at a Dye Plant NUMERATOR BENZIDINE EXPOSURE ONLY EXPOSURE TO BENZIDINE ANO/OR OTHER POTENTIAL CARCINOGENIC AGENTS* No. of reported eases of bladder tumor (1930-Mey, 1975) No. of cases occurring In group tint exposed prior to 1955 end diagnosed by May. 1975 No. of cases occurring In group first exposed between 1935-54 and diagnosed by 1955 (See Figure* 1 2) No. of cases occurring in group first exposed Since 1955 36 36 10 0 115 115 19 0 *tnciwlinii beia naphihyUmiM, crude alpha napbUiylainioe ami onto loluktoe. * been effective in preventing bladder tumors. Because of the long average induction period of about IS years,1 earlier comparisons would have been statistically unconvincing. Statistical analysis of case data A frequent problem in performing a statistical analysis to determine if there has been a sig nificant reduction in morbidity, c.g. bladder tumors, is the paucity of epidemiological data on the exposed population. The "numerators'* or data on the bladder tumor cases may be known reasonably well through medical reports and compensation claims (See Table I). How ever, the "denominators" may not be well Figure 1 -Reported number ot bladder cases, benzidine exposure only, 36 cases. 64 January, 1976 Mzjnosiandum fafiom wi>.^ Corporate Medical Department W.D. Harris, Industrial Toxicologist - 0 f7 &Q Jca/iru M4M SL&uJt o^ yy%u - ^2Le, CAj*U ftftZltAyij[ ^L6^\H^Ct *Atrvc^^ <Js4AJi * ^ Ajuuwa ^ Ut^* jh ZUdT m c^t^t C4AX y t/N3U^ ^ibCZLc^C- *** ,-AJcU ^veXZg Usod*M^y \JL$ *' c 33 cn OcnJ URL 15537 <fi4A 'V'siaJ- t{h+Zs-v\ ' MiM *2,TOXICOLOGY AND ARfLIED PHARMACOLOGY I-10 (19*2) URL 15538 The Effect of Vinyl CNoodeExposure on Rat Hepatic Metabolizing Enzymes1 Julie T. Du,2 Michael T. Tseng, and Carlo H. Tamrurro3 Liver Research Cemer. Division of DiftJlive Diseases and Nutrition. Deportments of Medicine and Anatomy, and Regional Cancer Center. University of Louisville School of Medicine, Louisville. Kentucky 40292 Received July 17, 1980; accepted September 12, 1981 The Effect of Repeated Viayl Chloride Exposure os Rat Hepatic MeiaboUziag Enzyme*. Du, J. T , Tseng, M T., andTamuurro, C H. (19*2). Toxicol. Appi Pharmacol. *2, I10. Sprague-Duwiey rau were exposed to 2.1% vinyl chloride Tor 2 (70 hr). 4 (140 hr), and < (210 hr) weeks to determine the sequential biochemical changes related to the oxidation and detoxification ability of hepatic tissue. Glutathionc-5-traaxlcraae<s) activity using 1,2epoxy-Ot-nitrophenoxy)propenc aed p-Rttrobcnzyl chloride as subetratee was elevated 17 to 24, 21, aed 25 to 42% after 2, 4. and 6 weeks of exposure, respectively, suggesting eezyme(i) inductioa. Reduced glutathione, the major substrate required to conjugate the toxic metabolites of viayl chloride, was abo consistently elevated. Similarly, the activity ofglutathione reductase, the enzyme necessary for the regeneration of reduend glutathione from its oxidized fora, was also increased following vinyl chloride exposure. Cytochromes R-450, the major protein in volved with vinyl chloride metabolism, was reduced after vinyl chloride exposure, confirming reports of others that viayl chloride metabolites destroy R-450. No abnormalities of standard clinical biochemical blood tests of liver function were found during 6 weeks of vinyl chloride exposure. The only consistent ultrastructural modification was the dilation of endoplasmic reticulum. The biochemical and ultrastructural alterations could reflect early hepatocellular adaptation to vinyl chloride exposure. Vinyl chloride, at high concentrations, has been shown to be carcinogenic in both lab oratory animals (Maltoai and Lefeminc, 1975; Viola tt a/., 1971) and man (Creech and Johnson, 1974). Present data support the metabolism of vinyl chloride by hepatic microsomal mixed-function oxidase system inlo toxic intermediates, ehkroelhyh;ne ox ide (bolt at ttl, 1975; Hefner et at., 1975; Kappus et at., 1976) and chioroacetaldehyde ' This work was supported by a grant from the Man ufacturing Chemists Association, Washington. DC. Portions of this study have been prcacatcd (Fed. Proc. 37, 1545, 1971). 1 Present address: Clement Associates, Inc.. 1010 Wisconsin Avenue, N.W., Suite 660, Washington, D.C. 20007. 1 Address requests for reprints to: Carlo H. Ttmburro. University of Louisville. (Gross and Freiberg, 1969). These two in termediates are considered to be the ultimate carcinogens (Barbia et at., 1975; Jaeger et at., 1974b; Van Duuren, 1975), lo be mu tagenic in bacterial systems (Elmore el at., 1976; Greim et at1975; Malaveille et at., 1975; McCann el at., 1975), to act us an alkylaling agent by reacting with adenosine (Barbin et at., 1975) and cytidine (Laib and Bolt, 1978), and to bind with protein (Bolt et at., 1976; Kappus et at., 1976; Watanabe et at., 1978). Detoxification of these metab olites occurs mainly by conjugation with glu tathione and is catalyzed by hepatic gluta thione transferases; the conjugates are excreted in the urine as substituted cysteine derivatives (Watanabe et at., 1976b,c; Green and Hathway, 1975, 1977). Chloroacetaldehyde can be further oxidized to chloro- ] 0041-90CX/S2/01000MOS02.00/0 Cmrn*< e mi w ammc it 1112 CHEMICAL REGULATION REPORTER The hotline telephone number is toll-free (800) 424-9346, or in Washington. D C., (202) 382-3000. The agency noted that this is a new local number for the RCRA/SUPERFUND hotline and should be used in place of all previously pub lished hotline numbers. The hotline only should be used for information on the superfund and not for reporting hazardous substance spills. These must continue to be reported to the National Response Center at (800) 424-8802. Radioactiv* Wait* HIGH-LEVEL WASTE RULES TO BE PROPOSED IN FEBRUARY, ACCORDING TO EPA OFFICIALS Standards and federal radiation guidance for the manage ment and disposal of high-level radioactive wastes and spent nuclear fuel probably will be proposed in mid-February, according to Environmental Protection Agency officials. According to internal agency documents, which were used in a briefing session presented by agency staff to EPA Deputy Administrator John Hernandez, Subpart A of the rule proposal, Standards for Management and Storage, would extend the exposure limits being developed by the Nuclear Regulatory Commission to waste management operations. Transportation of wastes would not be included as a waste management operation, according to the documents. Subpart B, Standards for Disposal, would set limits on projected releases from stored wastes over a 10.000-year period. The appendix to the standards would contain the Federal Radiation Guidance for Disposal, according to the briefing materials. Gordon Burley, director of EPA's Office of Radiation Programs, told BNA Jan. 20 that the standards are under high-level agency review and are expected to be issued in about four weeks. Burley said the proposal also is being reviewed by OMB. Administration EPA NAME8 10 NEW ATTORNEYS, ESTABLISHES CRIMINAL ENFORCEMENT UNIT Ten attorneys were appointed to fill key slots in the Environmental Protection Agency's recently reorganized enforcement section, and a new criminal enforcement unit was created to crack down on flagrant violations of environ mental law, according to a Jan. 19 agency announcement Enforcement counsel William A. Sullivan, Jr., said the new appointments to the reorganized Office of Enforcement Counsel (Current Report, Dec. 11, 1981, p. 995) include Sanford Harvey Jr., deputy associate enforcement counsel, who will be in charge of pesticides and toxics enforcement and Michael S. Alushin, director of the Office of Special Projects, who will supervise superfund expenditures for hazardous waste sites. Other enforcement appointments included: Geoffrey Grubbs, as director of the Office of Enforce ment Policy; Gerald Bryan, as director of the Office of Legal Oper ations; and, Peter G. Beeson, as director of the Office of Criminal Enforcement. Criminal Enforcement Unit The agency also announced the hiring of 2S experienced criminal investigators to form the core of a new criminal enforcement unit that will crack down on flagrant violations of environmental laws, including illegal discharges of wastes into waterways, so-called midnight dumping of toxic chemicals, and deliberate destruction or falsification of environmental records. The new Office of Criminal Enforcement will focus on activities that have resulted in substantial environmental harm and human health hazard and on those reflecting willful contempt of court-ordered consent decrees, accord ing to EPA Administrator Anne M. Gorsuch. Hoaith Hazard* CANCER DEATHS OF FORMER EMPLOYEES LINKED TO SPECIFIC MONSANTO WORK SITES Cancer deaths among former employees of the Monsanto Chemical Co. plant in Springfield, Mass., may be linked to exposure to materials used at specific work sites, according to a University of Massachusetts study. The study, conducted by a group of university toxicology graduate students, investigated the deaths of 110 males who worked in the plant and found that 34 had cancer that may have been work related. Kenneth Rosenman, who headed the study, told BNA Jan. 19 that the research team found increased cancer associated with exposure to vinyl chloride. The death of one former employee was due to liver cancer while several other for mer workers had mouth, digestive, lymphatic, and lung cancer. Rosenman said previous studies looked into the cancer deaths of former employees at the Springfield plant, but these studies included all workers, thus "diluting the studies' results." He noted that his study focused only on the work sites where employees were exposed to vinyl chloride and polyvinyl chloride. Rosenman said that, when he submitted his report to the company last summer, he suggested that it conduct addition al occupational studies, concentrating on particular work sites rather than the overall workforce at the Springfield plant. Pmaticidoa EPA PUBLISHES TOLERANCE AMENDMENTS, APPROVES CHLORPYRJFOS TEMPORARY TOLERANCE The Environmental Protection Agency Jan. IS through 21 established two pesticide tolerances, proposed one tolerance exemption, and granted one temporary tolerance. Tolerance Amendment* The agency Jan. 20 established a tolerance for bromoxynil at 0.1 parts per million on the following raw agricultural commodities (47 FR 2862): flax seed; flax straw; meat, fat, and meat byproducts of cattle, goats, hogs, horses, and sheep; oat grain; oat forage (green); oat straw; rye grain; rye forage (green); rye straw; wheat grain; wheat forage (green); and wheat straw. For further information contact Robert Taylor, Registra tion Division (TS-767C), Office of Pesticide Programs, EPA. 1-22-82 Copyright O 1982 by Th Bureau of National Affairs. Inc. <na-7973/e2/Soo so