Document pBxLo6janO8O8EQJkgewo4gLD

PUBLISHED REFERENCES TO THE BIOLOGICAL EFFECTS OF VIIJYL CHLORIDE INCLUDING CHEMICAL ABSTRACTS 1907-JANUARY 14, 1974 AMD BIOLOGICAL ABSTRACTS 1962-1973. f jT Assembled in chronological order by: THE DOW CHEMICAL COMPANY January, 1974 Revised June, 1974 Although this compilation contains most of the references to the biological effects of vinyl chloride as related to mammalian toxicity, the compilation should not be considered as exhaustive. 11 1 '``f*!r"J" v-i-1. " "" 1 R&S 025667 *1 THE TOXIC] TV OF V1IIYL CMLOPim: VAPOR A Brief Summary of liiic1 Publ i shod Literature June 20, 1074 The following articles and abstracts are believed to include most of the significant toxicological and medical references to the toxicology of vinyl chloride monomer in man and animals. The articles and abstracts arc arranged in chronological order. Article.'; published in the last half of 1973 and in 1974 may not be included if they have not been abstracted by Chemical Abstracts or Biological Abstracts. Important review articles which summarize much of the old literature have been used to cover the literature prior to 1961-1962. Therefore, copies of certain articles and abstracts described in these early reviews arc not included in this compilation. Translations of some articles are included. Since vinyl chloride (chlorocthcnc, CH^=CIIC,l) is a gas at room temperature and pressure, the common route of toxic exposure is by inhalation. As with many liquified gases, contact of the skin or eyes with escaping compressed vinyl chloride can produce freezing and frostbite. (Torkelson et al, 1961) . Vinyl chloride has long been considered to be very low in toxicity by acute inhalation. Lehmann and Flury (1938) summarized the literature and reported work by Schauman (1934, 1936) who considered vinyl chloride to be a candidate surgical anesthetic. Schauman reported little pathological changes oven after repeated exposure to anesthetic concentra tions. Further work on the anesthetic potential of vinyl chloride was reported by Krantz ct al, 1936 , Ostcr ct a 1, 1947 and Carr et al, 1949, who concluded that vinyl chloride was unsafe for use as a surgical anesthetic in dogs and that its use in man is unwarranted. W. F. von Octtingen (1955) of the U. S. Public Health Service summarized the available toxicity data on many halogenated hydrocarbons in an excellent monograph. According to von Octtingen, several authors had reported vinyl chloride to be rapidly absorbed and excreted_through the lungs and to cause anesthesia. The following is von Octtingen's summary of the toxicity of vinyl chloride in animals and man: "As to the tovie-i l-]t of vinyl chloride, Patty, Yant, and Wnitc (1930) studied this in guinea pigs. They found that R&S 025668 2- - exposuro to 20 to 40 vol. percent kills the: animals in a very short time, that concentrations of 10 vol. percent arc dangerous to life with exposures for 30 to GO minutes;, and that 0.5 vol. percent is the maximum allowable concen tration for several hours' exposure without causing acute disturbances of severe nature. Animals exposed in this way showed some edema of the lungs and hyperemia of liver and kidneys. They considered vinyl chloride less harmful than chloroform or carbon tetrachloride and of a similar order of toxicity as ethyl chloride. Schaurnann (1930) found that mice and rats tolerate repeated light narcosis tor 4 hours daily on 5 to 8 consecutive days and for 1 hour daily for 4 weeks without showing kidney or liver injuries. Dogs which had been narcotized for 3 hours with 10 vol. percent on 7 occasions in the course of several weeks showed no consider able changes in kidney and liver. Higher concentrations (20 vol. percent) caused in dogs marked salivation, respiratory arrest, and vomiting after narcosis. Peoples and Leake (1933) determined the lethal range for mice with 10 minutes' exposure as 10 to 12 mM per liter, and Schaurnann (1934) determined the vinyl chloride level in the blood at tile time of cardiac arrest as <40 mg percent and at the time of respiratory arrest as 27 to 30 mg percent, the same value for chloroform being GO to 70 mg percent. Regarding the -'0X7 G it\j of vinyl chloride oi' nor.. Pattv, Yant, and Waite (1930) expressed the opinion that the gas does not possess adequate warning properties because of its odor or irritant action, but that it gives warning by producing symptoms of dizziness and disorientation in advance of harm, except when present in exceedingly high concentrations which would cause almost immediately help lessness and unconsciousness. Inhalation of 2.5 percent will soon cause dizziness, disorientation, and a burning sensation in the soles of the feet, which symptoms disappear immediately after discontinuation of the exposure except for a slight headache which may last 30 minutes. These authors suggested the use of vinyl chloride for narcosis in man." Despite the early reports ascribing low toxicity to vinyl chloride, injury during the production of polyvinyl chloride (PVC) resins was reported as early as 1949. Significantly this report came from Europe (Russia) . Production of PVC in Europe preceded U. S. production by several years and today the quantity produced in Europe still exceeds U. S. production by about two fold. In 1949 , Tribuhk et al reported numerous effects in PVC workers in what by today's standards must be considered as primitive production facilities Those authors recognized that in addition to vinyl chloride numerous other materials, (plasticizers, stabilizers, break down products, etc.) were probably involved. The authors findings are as follows: & 30 (/> Oro cn CT> CT> CO -3- "1. The volat.no suljutmicoa formed when vinyl chloride: rosin and plasticized rosins arc subjected to boat treatment in production include organic chlorine compounds, hydrocarbons, vapors of free hydrochloric: acid, and carbon monoxide. 2. The action of these volatile substances is manifested in irritation of the mucous membrane chiefly of the upper respiratory passage; protracted action by the highly dispersed dust and vapors of vinyl chloride resin additionally causes dryness and atrophy of the mucous membrane of the upper respiratory passages, and also contributes towards the develop ment of chronic bronchitis. 3. The considerable number of cases of hepatitis among the workers examined, as well as the changes in the upper respiratory passages, raise the question of the need for further close observation of the state of health of workers and the taking of a number of therapeutic and prophylactic measures, particularly organization of warm humid (alkaline) inhalation of medicinal substances for workers. 4. With chlorinated diphenyl used as a vinyl chloride plasticizer, cutaneous affections such as acne, with predominant localization on the face and neck, were observed in the majority of the workers. 5. The following array of sanitation measures is required to prevent skin diseases during work with chlorinated diphenyl: 1) provision of protective underwear and outer clothing for the workers; 2) insulation of a shower room of the sanitation control station type, with individual dressing rooms for street clothing and work clothing. The sanitation control station should be outfitted with a steam room for steaming these protective underwear and clothing at a temperature of 110-120 for an hour. The shop should be provided with wash stands with hot and cold water. 6. In order to sanitize the ambient air it is necessary to decrease as much as possible the extent of decomposition of the vinyl chloride resin when subjected to heat treatment. This can be achieved by standardizing its thermal stability, and also by regulating the temperatures to which the rollers, presses, and other equipment arc heated, so as to prevent the temperature from exceeding 120-130. Of extremely great importance is efficient organization of the ventilation system with the aim of achieving maximum coverage of the sources of liberation of gases, vapors and dust. In view of the fact that cases of ignition of the condensate form in the ventilation exhaust pipes on contact with open R&S 025670 i ***jss.' .vv'Vt -4- flamc have been observed at some plants, in the designing of exhaust systems the specifications given in legislation governing construction for systems designed for the transmission of combustible gaseous mixtures must be complied with." As a result of two deaths in Canada, nanxiger <1960) , the acute inhalation toxicity of vinyl chloride was studied by Mastromattco et a 1 (1960) who reported that exposure of mice, rats, and guinea pigs to 10, 20, and 30 volume percent vinyl chloride caused the following mortality: NUMBER OF DEATHS 111 DIFFERENT GROUPS OF FIVE MICE, RATS AND GUINEA PIGS EXPOSED FOR THIRTY MINUTES TO VARYING CONCENTRA TIONS OF VINYL CHLORIDE III AIR Vinyl chloride concentration (percent by volume in air) Mice Laboratory animal Rats Guinea pigs Total 10 0/5 0/5 0/5 0/15 20 1/5 0/5 0/5 1/15 30 5/5 5/5 1/5* 11/15 40 " 2/5* 2/5 * A delayed death occurred within 24 hours following exposure. Some pulmonary hyperemia and engorgement was observed by these investigators, but liver and kidney injury were remarkably low. Deaths were due to narcosis. The first report of studies to determine the effect of long-term repeated exposure (6 months) were summarized by Torkelson, Oyen and Rowe (1961) as follows: "Repeated exposures of laboratory animals to several concen trations of vinyl chloride in air were conducted to determine the chronic toxicity of this material towards animals in order to assess the hazard to humans. Vinyl chloride was found to have a slight capacity to cause liver and kidney injury on repeated exposures. Male and female rats showed micropathological changes after repeated daily 7-hour exposures at 500 ppm for 4.5 months. Repeated 7-hour exposures at 200 ppm for six months resulted in micropathological changes i ;"v,-jw T- - J- in tlic livers of rabbits and k La tin tica 1 ly s iej ni f i.can t incrumitiK in the average woicjht of the livers of male and female rat:; but no do tee table changes in dog:; and guinea pigs. Repeated 7-hour exposures at 100 ppm resulted in slight increase:; in the average weight of rat livers, the other specie;; were not affected. All species studied tolerated repeated daily 7-hour exposure;; to 50 ppm fox. six months with no detectable ' injury. Repeated daily 1-hour exposures at 200 and 100 ppm of vinyl chloride wore without effect, longer exposures caused a slight increase in liver weight. The standard for evaluating regular daily 7 to 8-hour exposures may be defined as the concentration below which practically all analytical results must fall. The value of 100 ppm is suggested as this standard for, vinyl chloride, with a timeweighted average for all exposures not to exceed 50 ppm." Lester, Greenberg, and Adams (1963) took strong exception to the conclusion of Torkclson ct a 1 (1961) that 50 ppm should bo a maximum time weighted average exposure for workers. On the basis of 3 months exposure of rats to 2 volume percent and 19 days to 5 volume percent, they concluded that 500 ppm was acceptable as a TLV despite minor changes which they observed in rat livers and which they considered "were within the normal range and were not pathologic in nature." Because of these conflicting reports, the TLV Committee of the ACGII1 in 196 3 chose to change their TLV from 500 ppm as a maximum time-weighted average for industrial exposure to 500 ppm as a ceiling value. (American Conference Governmental Industrial Hygiene, 1963). Kuebler (1964) reported that repeated 2-hour daily exposures to 0.5, 1.5 or 5.0 volume percent (5,000, 15,000 <_.nd 50,000 ppm) caused no histological injury in rats, mice or guinea pigs . Since 1949 numerous articles describing conditions and problems in PVC production plants have appeared particularly in the Eastern European literature. Filatova and Gronsborg (1957), Gabor ct al (1962), Suciu ct al (1963), Gabor ct al (1964), Grigorcscu and Toba (.1064), Antonyuzhcnko (1968), and Kudryavtseva (1970), have all described the effects of apparently gross chronic exposure. These papers and abstracts arc difficult to interpret since there arc generally inadequate descriptions of the exposure conditions and analysis of the workroom air, so no dose-response relationship can be dotoimi nod. The injuries and effects described by the authors are not con sistent with the levels of exposures claimed by the authors f '. h JO CO > Or ro cn j o> /o t I t* il 6- - nor are the levels of exposure consistent with past or even present-day chemical technology. furthermore, mixtures of chemicals are involved making it impossible to ascribe the effec' to any one of them. For example, Suciu c t a 1 (196 3) (through Translation) described nervous disorders including euphoria with whistling and laughing, incoordination and dizziness similar to alcohol intoxications However, fiuciu ct: a.1. ascribes these results to exposure of the order of 5,9 my/m (2 ppm v/v) which is not consistent with other publications which indicate those effects will he apparent only if concentrations greatly exceed 10,000 to'20,000 ppm v/v (Lehmann and Flurv (1938), von Oettinyon (1955), Lester ct a 1 (1963). Therefore, the following conclusions by the authors can be construed as being tile result of massive and apparently repeated exposures; 1. Vinyl chloride and the vinyl monomers possess a narcotic action and produce, depending upon concentration, in addition to characteristic neurologic manifestations, a state of euphoria (125), followed by a state of in ebriation similar to that of alcohol, intoxication. i.n certain cases narcosis can appear. After leaving the working environment, a state of somnolence (45?.) persists, with hypersomnia. Vinyl chloride acts on the skin and produces a sensation of formication and of heat. 2. After repeated exposure, a neurologic asthenia sets in m which somnolence predominates. 3. After a variable period of time, dyspeptic disturbances are added to the neurologic manifestations; these first not characteristic; they are in the form of epigastric pains (16?), swelling, discomfort, feel:::' of heaviness in the right hvpochondriurn (73) or tin. (5%) with anorexia, particularly for fats. In 30.2% of the cases, congcntivc hepatomegaly npp- . which may mimic toxic hepatitis without jaundice; : cases may become chronic. In 6% of the cases, the hepatomegaly is aecomp.e splenomegaly. The protcinogram and the aldolases are the most sensitive tests and show changes sir-' those of acute hepatitis; increase in u-globu!i:x, of the (1- and y-globulins; the thymol test, reaction and the zinc sulfate tost are p;. s few of the cases. C^9S20 jj So V) 'o A. After 3 years of exposure in 9" of the ease:; a syndrome typical of ulcer without rad i oi og i <: changes becoim :r. manifest. 5. In 6".', of tile c.ises tlie Raynaud syndrome liar. appeared, particularly among the young men. I'l o thysmog raphy show:; in half of the oases an inhibition of the vasomotor centers. G. In addition, allergic dermatitis in A.A'l of the case:;, and scleroderma in 3.G", has been observed. 7. The clinical and laboratory findings are of great importance in occupational pathology because in numerous cases diseases appear in man that cannot be reproduced in the animal (Raynaud's syndrome and scleroderma). The sudden and frequent appearance of these manifestations in the PVC division of several plants, and in certain divisions in normal individuals who arc still relatively young, and their disappearance in the majority of the cases after the institution of protective measures and change of work, have shown us decisively that vinyl chloride and the vinyl monomers have played a part in the production of these manifestations. (End of author's summary). In 19G7, reports appeared in the literature describing a condition known as acroostcolysis in workmen engaged in polymerization of vinyl chloride to polyvinyl chloride. Harris and Adams (1967) reported on two cases in Europe. Wilson ct al (1967), reported on 37 cases in the B. F. Goodrich Company. BasaJ^jv (1970) described the use of large frame photofluorography for diagnosis of acroostcolysis in Russia. Basalaev ct a1 ( 1972) described studies in rats and rabbits and claimed to have produced the disease in these species. Fcthierc and Kcrzncr (1972) discussed the disease * as did Jiihc ot al of the University of Bonn (1973) . Juho et al (1973) described a syndrome consisting of (arranged in decreasing order of occurrence) thrombopenia, splenomegaly, liver damage, obstruction of ventillatj.on, circulatory obstruction, and skin and bone alteration. As a result of this problem, the University of Michigan in 19G7 was retained by the Manufacturing Chemists Association to investigate acroostcolysis in sponsoring American companies. The results of a large scale epidemiological study of workers then currently employed in vinyl chloride and polyvinyl chloride production were reported in three publications by by this group (Dinman ot al, (1971) Cook ot a 1, (1971) and Dodson ot a1, (1971)). .ifjfim * R&S 025674 8- - Dinman ot a 1 surruuari xed tin; study as follow:;: "An opj driniolccjicnl study wan performed covciri ng 5,011 employee.'; with 21,510 man-years experience in various phases of vinyl chloride (VC) and polyvinyl chloride (PVC) manu facturing in 32 plants throughout the Uni l cd .States and Canada, The total number of definitive cases of acroos tooly.s is (AOL) war. 25; 16 other individuals were under suspicion. Tliis condition is clearly associated with the hand cleaning of polymer!xors. Workers engaged in other phases of VC or PVC manufacturing do not appear to he at risk of developing AOL, Tire .importance of Raynaud's phenomenon as a con comitant of AOL is emphasised. Ilovoral statistical approaches for rapid medical survey arc suggested. Acroos Leolysis appears to be a systemic rather than local disease. Presently, neither the etiological agent nor its portal of entry is known. Cook gt al describes the polyvinyl chloride production process in considerable detail. They concluded that although no etiological agent could be identified, '"''here appeared to be a correlation between the extent of degassing prior to entry into the reactor" and the incidence of acroostcolysis. Mutchlcr and Kramer presented a paper at the 1968 Gordon Research Conference which was subsequently published (1972), which reported on "The Correlation of Clinical and environ mental Measurements for Workers bxposed to Vinyl Cnloridc". The authors drew the following conclusion: "Our findings suggest that repeated exposure to vinyl chloride at TWA levels of 300 ppm or above for a working lifetime toycther with a very low level of vinylideno chloride may result in slight changes in certain physiologic and clinical laboratory parameters. The possibility of some impairment in liver function tests must be considered, even though no overt clinical disease was evident in any of the individuals studied. We shall continue our study, but suggest that similar studies to help clarify the effects of this material bo performed for other worker populations exposed to vinyl chloride alone." The study by Dinmnn et al, together with the study by Mutchlcr and Kramer, appear to be the only two significant epidemiological studies on vinyl chloride workers reported in the literature prior to 1974, but neither study was designed to evaluate the incidence of cancer. P. L. Viola, in an attempt to produce ucroostoolysis in animals, exposed rats 4 hours per day, 5 days per week to 30,000 ppm (3t) vinyl chloride vapor. (Viola, March, 1970). In his first report on the results of 12 months exposure. R&S 025675 -9- hc described me tap] ns tic: changes in the bone:; which he con sidered sijii.il/ir to the human disease acroos teolys j. He made no mention of having observed cancer in these animi.il s until the Tenth International Cancer Cojigress in /lay, 1970. In the abstracts of this moating, (Viola, 1970), and sub sequently in May, 1971, Viola, Bigotti and Caputo (1971) reported tumors of the skin, lungs and bone:; occurring f i. rs t after 10 months of exposure. The authors summarized this work as follows: "Rats (Ar/IRE Wistar strain) exposed for 12 months to vapors of vinyl chloride developed tumors of the skin, lungs, and bones. The cutaneous tumors, which always appeared in the area in which submaxillary and parotid glands are located, have been histologically recognized as epidermoid carcinomas, papillomas, and mucoepidermoid carcinomas. The morphological characteristics of lung tumors, which occurred in a lower percentage, were mainly of the adenocarcinoma type, with the exception of a single epidermoid tumor originating from the epithelial covering colls. In a minor number of rats, a large proliferation of cartilaginous tissue diagnosed as osteochondroma developed in chc metacarpal and metatarsal regions of the four limbs." This report by Viola ct a 1 is apparently the earliest publication in which carcinogenic activity has been ascribed to vinyl chloride in man or animals. Although there wore obvious deficiencies in Viola's study, such as his very impure sample, the presence of food and bedding in the exposure chamber, the excessive exposure concentration as well as in the statistical evaluation and interpretation of the lesions, the report was of serious concern and resulted in additional animal and epidemiological studies which are currently underway in Italy (Maltoni, 1974 ; Maltoni and Lcfcrnine, 1974) and the U. S. (Keplingcr et a1 , 1974) . On January 22-23, 1974, the B. F. Goodrich Company notified its employees, NI0SI1, the Kentucky State Department of Labor, and the public, that three workers had died of angiosarcomas of the liver. The case reports of the first subject has been published by Creech and Johnson (1974) . The subject, a 36 year old male, was hospitalized January 5, 1970 and subsequently succumbed September 27, 1971. he had worked in PVC production from November 1959 until his illness. The history, clinical course and pathologic findings arc consistent with the others who died of angiosarcoma. The work of Maltoni and Lefemine (1974) lias 'neon reported publicly at the OSI1A hearing, Washington, D.C., February 15, 1974, and included in the 1974 publication of the Second Inter national Symposium on Cancer Detection and Prevention, Bologna, Italy, April 9-12 , 19 73. 1'n those studies groups of rats as well as mice and hamsters have been exposed to concentrations R&S 025676 -10- of 10,000 to 50 ppm vinyl chloride- vnpor . Maitoni .md J,e forni no (1974) rf.'jior ted on roi nora;i:; of (he.- Zyrnbui g .lands, nephrobl.is Loma and nng i os.ircom.is of the livers. of rat:; a I. concentration:; of 250 ppm to 10,000 ppm but not at 50 ppm. Subsequent information not yet published but. presented at. the Mew York Academy of Science May 10 , 1 974 indicated an ang.i onu rcoinu wns observed in a very old rat which had boon exposed to 50 ppm for one: year and kept for over 20 months follow: ikj exposure. Mice wore also reported by Maltoni. and Lofomino to have developed tumors at 50 ppm and hicjhor (Experiment 1;T of the 1974 report) . Tumors of other organs wore also reported in rats exposed to 250 ppm and higher. In their experiment BT Maltoni and Lefemino reported possible in utero production of .angiosarcomas in offspring of pregnant rats exposed to 10,000 and G,000 ppm. Keplinger et al (1974) in a study sponsored by American companies have confirmed the findings of Maltoni and I.efomine. In this study groups of 100 rats, mice and hamsters, of each sex are being exposed seven hours per day, five days per week to cither 2,500 , 200 or 50 ppm vinyl chloride monomer. /after seven months of exposure angiosarcoma and lung adenomas have berm observed in mice at all exposure levels. Although the data are preliminary in nature and require confirmation, angiosarcomas were apparently also observed in rats at 2,500 and 200 ppm and in a single hamster at 2,500 ppm. This study is still in progress and will not be completed until 1970 or 1977. Epidemiological studies on t'. S. workers have been conducted by Tabershaw-Cooper Associates for the Manufacturing Chemists Association. The data were presented May 1.0 at the Mew York Academy of Science and a copy of the final report is included (Tabershaw-Cooper Associates, 1974). The summary of this report is as follows: 1. The overall mortality of the study population was approximately 75 percent of what would be expected in a comparable population of U. S. males. 2. Ho cause of death showed a statistically significant excess over what would be expected in a comparable U. S. male population. 3. No new deaths identified as angiosarcoma of the livi.-r were found. 4. All previously known angiosarcoma death.:; in the study population during the study period were found as part of tile routine study procedure. 5. Cancers, of Lho liver (primarily angiosarcoma), respira tory ::ysteiu, brain, and cancers, of unknown primary site, R&S 025678 -li as well as lymphosarcoma, occurred more often than expected in those members of the study population wi th tile greatest exposure. Oven though the excesses were not statistically significant, the findings warrant further s tu dy. 6. Other cancers occurred at lower levels than in tire general male population, with the exception of cancers of the buccal cavity and pharynx. There was an excess of these cancers, which however was inversely related to exposure. The explanation for this finding is not apparent. June 20, 1974 chronological lift nr Ri,ri:p.i:;;ri;:: Pat. ty, F. A., W. P. Yant and C. P. Waji.c. Acute rosnonsc of rjui nc;i pigs to vapors of some now comir/j re i a 1 organic compound:; V. V j nyl Ch 1 or.i do , N. C. I'iiIj] ic Ileal Lb Reports 4_5, 1 9 6 3- ] 0 7 1 . Abs t. rac; t on 1 y . 19 30. Frantz, J. C., C. .J . Carr, R. Musser ,ind W. C,. Ilarne, The effect of chlorinated ethy lone:; on 1.1 jr- perfused leg vessels, of the frog. Arch Intern Pharma codynamio 5_2, 309-72. Abs tract only. 19 30 . Lehman, K. B. , and F. Flury. "'ox.i oology and hygiene of industrial solvent:;. 1930. As translated by Lleanor King and Henry F, Smyth, Jr. 1941. Flinn, F. B. Industrial exposure to clrlorinatcd hydrocarbons. American Journal Medicine, i, 380-394, Abstract only. 1946. Ostor, R. 11., C. J. Carr, J. C. Frantz and f".. J. Sauerwald. Anesthesia XXVII Narcosis with vinyl chloride. Anesthesiology, R_, 399-361, Abstract only. 194 7. Carr, C. J., R. M. Burgison, J. F. vitchn and J. C. Frantz. Anesthesia XXXIV Chemical Constitution of hydrocarbons and cardiac automaticity. J. Pharmacology and Fxperimental Therapeutics, 9_7, 1-3, Abstract only. 19 49. Tribukh, S. L., N. P. Tikhomirova, S. V. Levin and L. A. Fozlov. Working conditions and measures for their sanitation in the production and utilization of vinyl chloride plastic. Arg Sanit in, 38-45. Translation from Russian. 1949. Harris, D. K,, Health problems in the manufacture and use of plastics. British Journal of Industrial Medicine, 1J5, 255-268, Abstract only. 1953. Von Oettingcn, W. F., M.D. The halogonated aliphatic, olefinic, cyclic, aromatic, and aliphatic-aromatic hydrocarbons including the halogcnatcd insecticides, their toxicity and potential dangers. Public Health Service Publication No. 414, IJ. S. Department of Health, Lducation, and Welfare, Washington, D. C. 1955. Filatova, V. S. and F. Sh. Gronsborg, Sanitary hygienic conditions of work in the production of polyvinyl chloride resins and measures of improvement. Ciegienn 1 Sanit 22(1), 38-42. Abstract only. 1957. Filov, v. A. Thermodynamic activity of some industrial poisons -evaluation of the activity in the toxicology of volatile organic compounds. Tr. Nnuchn. Sessii honingr. Nauchn.-IssId. Inst. Gigieny Truda i Profzabolev, 223-31. Abstract only. 1959. R&S 025680 2 Dnnzigcr, II. Accidental poi I'.oni ng la/ vinyl ch 1 or i.d< : ReporL of two cases. Canadian Medical Ar; not; i a t.ion Journal 0 2 , 823. Through Mu r; t roin.i t U:o (; L a 1 , 1900. Mas tromu L too, V.. , A. M. Fisher, !!. Cl. r.i a Li e, and II. Danxiger. Acute inhalation toxicity of vinyl chloride1 to laboratory animals. American Induslrjul hygiene Association Journal, 21 (9) , '194-398. 19G0. Torkclson, T. R. , P. Oycn, and w. K. Howe. T!ic toxicity of vinyl c:hloridc as determined by repented exposure of laboratory animals. American Industrial Hygiene Association Journal, 2 2(9) , 35-1-361. 1961. Gabor, 5., M. Lecca-Radu, and I. Manta. Certain biochemical indexer, of the blood in workers exposed to toxic substances (benzene, chlorobenzene, vinyl chloride). Prom. Toksi.kol. 1 Klini.ka Prof. Zabolcvan i i Khim. PL.iol. Kb. 221-223. Abstract only. 1962. llock, W. W. and G. Piren. Growth of p.lanLs fumigated with saturated and unsaturated hydrocarbon gases and thc;i r derivatives. Texas A or. Lxnt, Gta. Misc. Publ. UP-60 3 , 12. Plant biochemistry, 1962. Irish, D. D. Vinyl clilori.de, CII.^CIiGl (M.onochloroethcno) . Industrial Hygiene and Toxicology, Volume- 2, pp. 1303-1305. F. A. Patty, Lditor. 1962. Lester, D., L. A. Greenberg, and W. R. Aciams. L'ffacts of si.ngla and repeated exposures of human;; and rats to vinyl chloride. American Ind.strial Hygiene Association Journal, 2_4, 265-275 . 1963. Suciu, I., I. Drejman and M. Valaskai. Investigations of the diseases produced by vinyl chloride. Medicine Interna (Bucharest), XV(8), 967-978, Romanian Article and translation. 1963. Burditt, A. K., Jr., F. G. Ilinman and J. W. Unlock. Screening of fumigants for toxicity to eggs and larvae of the oriental fruit fly and Mediterranean fruit fly. J. Peon, fntomol., 56(3), 261-2G5. Abstract only. 1963. Gabor, S., M. Rndu, N. Prcdn, S. Abrudcnn, L. Ivanof, Z. Anea, and C. Valnoxkay. Biochemicn 1 changes in workers occupied in vinyl chloride synthesis and polymerization. Igiena Bucharest 13 (5) , 409-418. /distract only. 1 964. Ilardie, D. W. F. Chlorocarbons and chlorohydrocurbons: vinyl chloride. Kirk-Othmer Hncycl. Chem. Tochnol., 2nd Ld. 5, 171-178. Abstract only. 1964. Kucblor, II. The physiological properties of aerosol propellants. Aerosol Age 9(4), 44, 47-48, 50, 90-91. Abstract only. 1964. 3 Mamedov, M. Vinyl chloride. Baku: Axerb. Go:;. I*/, cl. pp. 12 7. Abstract only. 19Gd . Burcj, S, P. and j;. A. Bury. Fthylono action and 1.1m: ripening fruit.1;. Science, 14 fj ( 3 6 7 4) p] an L-Grow l.li H< 'y u J a Lorn . I.fJCS. Gr igorcscu, J. and G. Toba. Viny.l cbloricie; .i ndus tr j a 1 toxicologic a:;pf'Cl.:;, Rev. Chim. .17(B), 4 9 9 - 3 01 . Abstract only . 19 G 6 . Harris, D. K. and W. G. F, Adairi:;. Acroos Loo] yh i s occurriny in men engaged in the polymerina Lion of vinyl chloride. Brit. Mad. Journal, 5 '16 7, 713-714. Abstract, only. 19G7. Wilson, R. H., W. b. McCormick, C. F. Tatum, and J. b. Creech. Occupational Acroostcolysis, report of 31 cases. The Journal of the American Medical Association, 201(8), 577-581. 1967. Vanin, A. M. , and F,. 1. Plokhova. Pathogenic effect of chronic exposure to vinyl chloride on rabbits. Farmakol Toksikol, 31(3), 369-372. Abstract only. 1968. Vanin, A, N., and F. X. Plokhova. Creation of an experimental model of "toxic nngioncurosis" developing from the chronic action of vinyl chloride vapors on an organism. GIG TR Prof Zabol 12(7), 47-49. Abstract only. 1968. An tony uzhenko, V. A. Occupational poisoning lay vinyl chloride. GIG TR Prof Znbol 12(3), 50-52. Abstract only. 1968. Baretta, F. D., R. D. Stewart, and J. F. Mutchlcr. Monitoring Exposures to vinyl chloride vapor: breath analysis and continuous air sampling. American Industrial Hygiene Association Journal, 30, 537-544. 1969. Vazin, A. M., and F. I. Plokhova. Dynamic changes in epinephrine-like substances in rabbit blood following chronic exposure to vinyl chloride fumes. GIG TR Prof Zabol 13 (6) , 46-47. Abstract only. 1969 . Clapp, J. J., C. M. Kayo, and L. Young. Metabolism of allyl compounds in the rat. Biochem. Journal 114 (.1 ) , 6-7. Abstract only. 1969 . Vazin, A. H., F. I. Plokhova. changes in adrenaline-like substances in rabbit blood following chronic exposure to vinyl chloride fumes. GIG TR Prof Zabol. 1 i(6) , 46-47. Abstract only. 19C9. Vazin, A. N., F. I. Plokhova. Changes in the cardiac activity of rats chronically exposed to vinyl chloride vapors. Farmakol Toksikol, 32(2), 220-222. Abstract only. 1969 . R&S 025681 r & i- -t- - j 4 Schottek, W. Toxicology of vinyl ch i o r i do, Choin. Tech. , 21 (11) , 708-7].1. Abs lir.ncL only. 1 969. Smirnova, 11. A., and 11. P. Grnnik. Long-term side effect.:; of nculc o<j(;u))i'i Liona] poison i ng by corl.ij n hy d roca rboj.. and their derivative:;, GIG TP Pro! Zabol 1/bLbL' -h-M. Abstract only. 1970. Basalaev, A. V. Experience w.ith the use of large-frame photofluorography in exam: ning skeletal bones ol per .sons occupationally dentine with unsaturated hydrocarbons of the ethylene series (olefins) and their chlorine deriva tives (vinyl chloride, trichloroethylene'. Gin Tk Prof Zabol 14(11), 34-37. Abstract only. 1970. Kudryavtseva, 0. F, Characteristics of electrocardio graphic changes in patients witli vinyl chloride poisoning. GIG TR Prof Zabol 14 (8) , 54-56. Abstract only. 1970 . Viola, P. L. Pathology of vinyl chloride. Medicine del Lavoro, 61(3), March, 1970. Translated from the Italian. 1970 . Viola, P. L. Canccrogenic effect of vinyl chloride. Prosai'. ted at the Tenth Int. Cancer Cong., lloux ton, Texas. May 22-29.. Author's Abstract. 1970 . Dinman, B.. D., W. A. Cook, W. M. Whi tehouse , li . J . Magnuson and T. Ditcheck. Occupational Acroos tcolysis: 1 . An Epidemiological Study, /archives of Environmental Health, 22, 61-73. 1971. Cook, W. A., P. M. Giever, B. D. Dinman, and H. J. Macjnuson. Occupational Acroos toolysis: II. 7.n Industrial Hygiene Study. Archives of Environmental Health, _22, 74-82. 1971. Dodson, V. H., B. D. Dinman, V?. M. Uhitohouse, A. H. M. Hasr, and II. J. Mngnuson. Occupational Acroos teolysis: III. A clinical study. Archives of Environmental Health, 22, 83--91. 1971. Viola, P. L., A. Bigotti, and A. Cnputo. oncogenic response of rat skin, lungs, and bones to vinyl chloride. Cancer Research, 31, 516-522. 1971. American Conference of Governmental Industrial Hygienists. Vinyl chloride. Documentation of the Threshold Limit Value, American Conference of Governmental Industrial Hygienists, Third Edition, 1971. Kramer, C. G., and J. E. Mutchler. The correlation of clinical and environmental measurements for workers exposed to vinyl chloride. American Industrial Hygiene Association Journal, 33(1), 19-30. 1971. R&S 025682 R&S 025683 t Mcyon;on, L. 13. and C. C. Meier. Cutaneous I <:r;i nn:; in l (icroo.',!.r:oly,';.i Arch Dermatol l_P/'_(_tl ' 224-227, Abu t. r .it; I. only. 197.7. Julie, S. , and C. K. Lange. bony-term cxjiociirt; to vinyl eh lorido . DU. fled, Wschr. 9_7, !: n J,iuh Al i.s l. me l.. 1972. Biir.aliiov, A. V., A. N, VaxJn and A. G, Kochetkov. Pathogenesis of changer; developing due t_o long-term exposure to the offeet of vinyl chloride. GIG TR Prof Zabol 16 (2) , 24-2 7. Abutract only. 1972. llarlov.'itx, S. S,, C. J. McDonald, W. Fethicro and r.. S. Kerxnor. Occupational acroostoolysin. Arch norrnatol 1 f) G (2 ) , 219-223 . Abstract only. 1972 . Juhe, S., C. E. Lange, G. Stein, and G. Voltman. Ubc.r die sogenannte Vi nvlchlor i.d-Krnnkhe.i t. Dtsch. mod. Wschr. 9 8 , 2034-2037. (German with English tram; 1 nt.i.on) . 1973. Levina, n. M. , V. S. Filatova, C. 0. lit,'lava, a. A. Ashirova, Y. P, Tikhomirov, A. L. Levin, U. v,. liont.i nskaya, and D. E. Kuzncfcskii. hygienic certification of the building projects dove lopmo n t, and reconstruction of plants pro ducing organochlori.no products. Gig. Sanit 10 7 3 ( 4) , 80-87. Abstract on.ly. 19 73. Filatova, V. S., V. K. Vinogradova, and L. S. Bashkirova. Hygienic evaluation of working conditions in some chemical plants operating in the open air. GIG TR Prof Zabol 1973 (8), 8-11. Abstract only. 1973. Marstcller, II. J., W. K. Lclbach, R. Mueller, S. Juche, C. E. Lange, It. G. Rohncr, and G. Voltman. Chronic liver damage in PVC production workers. German Medical Journal 98, 2311-2314. English Translation. 1973. Sokol, W. II., Y. Aolony and G. h. Beall. Moat Wrappers asthma Journal of the American Medical Association 2 2 6 (G) , 639-641. 1973. Maltoni, C. Occupational Carcinogenic. Proceedings of the Second International Symposium on Cancer Detection and Prevention, Bologna, April 9-12 , 1973. Excerptn Modion, Amsterdam. 1974. Maltoni, C. and G. Lefeminc. The potential of the planned experiment in the prediction of the risk of ambient carcinogens All example: vinyl chloride. Lincci-Rendiconte Della Clause di Science, Tcsiehe, Mnthmatisehe ilaturalo, S6_, 1-11 with English Translation. 1974. I f. Lange, C. K. , S. Julie, G. Stein and G. Veltman. Die Sogenante Vinylchloridc-Krankhcit-cin berufsbeding te Systems Klcrose? Int. Arch, /vrbeitsmed 32., 1-32. 1974. Creech, J. L. and M. M. Johnson. Angiosarcoma of Liver in the Manufacture of Polyvinyl Chloride. Journal of Occupational Medicine, 1fi (3) , 150-151. 1974. Tabershaw/Cooper Associates. Fpidcrniolqgi cal Study of Vinyl Chloride workers. Final Report to Manufacturing Chemists Association, May 3, 1974. Keplinger, M. L., J. W. Goode, D. E. Gordon and J. C. Calnndra. Interim results of exposure of rats, hamsters and mice to vinyl chloride. Annals of the hew York Academy of Sciences Working Group. Toxicity of Vinyl Chloride and Polyvinyl Chloride. May 10-11, 1974 In Preparation. 1974. R&S 025684