Document jyJzQRYYEYgJx21LVwBp37QGO

: tO o u> On -L OO ^1 August 22, 1980i 1962 Tho professional group conforms more nearly to the average for the entire population considered. Few conditions are found to havo excessive rates; but on the other hand, there are not very many with paTrthiceublaursliynelosswgrraotueps. approximates the average for the entire popula tion considered in nearly every respect. The skilled trade group stands out distinctly from the others in a number of respects. Its rates of impairments are excessively high for eye and ear, teeth, heart and pulse, and many miscellaneous conditions. The desirability of a atudy of the rates of impairments in the specific occupations making up this group is suggested. Again, it should be emphasized that one could not expect in this study to find very marked differences, since the lower social levels are but slightly represented in the data. ACKNOWLEDGMENTS The original 'data, prepared .up to the stage for tabulation, were made available to the Milbanlc Memorial Fund and the United States Public Health Service by the life Extension Institute. Per sonal acknowledgment, however, is due to Dr. Eugene Lyman Fisk, medical director of the institute, for bis valuable counsel, and Miss Elizabeth W. McKee, statistician, and the staff in general for their constant cooperation and frequent assistance on many details. REFERENCES _ ^3 q 2 fr> (*5 (X) Sydenstricker, Edgar, and Britten, Rollo H.: The physical impairments of adult life--General results of a statistical study of medical examinations by the Life Extension Institute of 100,024 white male life insurance policyholders since . ^ rn ' 1021. Journal of Hygiene, January, 1930. , x (2) Sydenstricker, Edgar, and Britten, Hollo H.: The physical impairments of ;rJ3 v- adult life--Prevalence at different ages, bused on medical examinations by tbs > i -< it Life Extension institute of 100,024 white male life insurance policyholders since B q ^ 1021. Journal of Hygiene, January, 1030. : 3 , x> ? (3) Collins, Selwyn D.: Economic status and health--A review and study '32 jE: of the relevant morbidity and mortality data. Public Health Bulletin No. 165, 5 s5> U.(S4). PRuebgliicstHraeraGlthenSeerravl'isce.Decennial Supplement, England and Wales,. 1021, Part II: Occupational mortality, fortuity, and infant mortality. London: 1027. fn (5) Britton, Hollo II.: Occupational mortality among males in England and Wales, 1021--1023.--A summary of tbo report of tho Uuglslrur General. Publio - Health Reports, U. S. Public Health Service, vol. 43, No. 25, June 22, 1028, pp. 1665-1616. Reprint No. 1233. Z00CC6PZ 1__9_6__3 August 22,1980 ACUTE RESPONSE OF GUINEA PIGS TO VAPORS OF SOME NEW COMMERCIAL ORGANIC COMPOUNDS V. VINlfL CHLORIDE1 By F. A. Patty, Assistant Physiological Chemist, W. P. Yant, Supervising Chemist, and C. P. Waite, Assistant Surgeon,* Health Laboratory Section,. Pittsburgh Experiment Station, Bureau of Mines \ This report on tho acute response of guinea pigs to vinyl chloride gas is the fifth of a series of similar reports which deal with studies pertinent to evaluating the hazards involved in exposure to some chemical products which havo recently reached, or promise to reach, important domestic and industrial use. The first report of the series dealt with ethylene dichloride, * tho second with ethyl benzene vapor/ tho third with "Cellosolve" (ethylene glycol monoethyl ether)/ and tho fourth with ethylene oxide/ Vinyl chloride is used at present only in the synthesis of organio compounds, principally resins. The investigation described herein was undertaken at the request of the Carbide & Carbon Chemicals Corporation, and the work was conducted jointly by that corporation and the United States Bureau of Mines at the Pittsburgh Experiment Station of the Bureau of Mines. scope ov work 1 The Bcope of the work included a study of tihe toxicity of vinyl,'' chloride and the physiological response to its vapors as determined by exposure of guinea pigs. Only acute effects as produced by a single exposure were studied. The experiments were planned to give information relative to the concentrations and periods of exposure which produce but slight response, moderate response, and serious response. 1 TbU report represents work dene undor cooperative agreement between tho Dureau of Mines, Depart ment of Commerce, and the Carbide A Carbon Chemicals Corporation. Published by permission of Ute Director, U. S. Bureau of Mines. Assistant surgeon. United States Public Health Service, detailed to the Bureau of Mines. Sayers, R. R., Yant, W. P., Waite, C. F., and Patty, F. A.: Acute response ofguinea pigs to vapora of some new commercial organio compounds. I. Ethylene dlchlorlde. Pub. Health Rep,, vnl. IS, No. A Jan. 31,1030, pp. 325-330. (Reprint No. Util.) 1 Yant, W. 1'., Schronk, II. II., Waite, O. P.,and Patty, F. A.: Acute response oi guinea pigs to vapors of some new commercial organio compounds. II. Ethyl bemono. Pub. Uoaltb Rep., vol. 40, No. 33, May , 1830, pp. 1341-1300. (Itoprlut No. 1378.) Wullu, C. 1'., 1`ully, K. A., uuit Yant, W. 1'.; Acute response o( guinea pigs to vapors oi some new commercial organio compounds. Ill, " Collosolve." Pub. Health Rep., vol. 40, No. 30, Jam 37, 183(1 PP. 1408-1400. (Reprint No. 1388.) Waite, O. P., Patty, FA., and Yant, IV. P.: Acuto response ofguinea pigs to vaporsofsome new com mercial organio compounds. IV. Etbyloae oxide. Pub. Health Rep., vol. 45, No. 33, Aug. 8, 1830, [pp. 1832-1B13. (Itoprlut No. 1401.) vl 1964 v DESCRIPTION OF MATERIAL USED FOR TESTS Vinyl chloride (CHjCHCl) is a colorless gas at room temporatures (boiling point, --13.9 C.). The gas has a pleasant ethereal odor and is slightly soluble in water. Its limits of inflammability are 4.0 to 21.T7hpeevr icneynlt'cbhylorviodleumuseedininaier.x7periments described in this report was a commercial product having the following plant specifications: Boiling range, 95 per cent or more below --10 C. at 760 nun.; acetaldehyde, not more than 0.5 per cent; residue, not more than 0.5 per cent. . TEST APPARATUS The test apparatus was the same as that described in a previous reportdealing with ethylene oxide.' COMPUTATION AND ANALYSIS OF GAS-AIR MIXTURES \ 8YMPTOMB or ANIMALS Control animals.--No symptoms were exhibited by the 18 control guinea pigs used in these tests or by the stock animals from which all of the tost animals wero taken. Also, no deaths occurred. V, Exposed, animals.--Table 1 gives the symptoms shown by the ani mals exposed to vapors of vinyl chloride and also the average period of exposure required to produce theso symptoms by various concen trations of vapor in air. The reader should note that the figures in parentheses indicate that the particular symptom did not occur in the maximum period of test as given. The highest concentration of vinyl chloride in air used in the expo sures (40 per cent) exerted an almost immediate narcotic effect on the animals. Within one-fourth minute the animals fell to their sides in an apparent unconscious or narcose state, with convulsive twitchings of the trunk and extremities and jerky rapid respirations. The pigs remained in this state until death or termination of the test. The vinyl chloride-air mixtures were created by adjusting calibrated flowmeters (Venturi type) to give the desired proportions of gas and air. The vinyl chloride content was then checked by analysis. The apparatus used was the same as that used for determining ethylene dichloride in air.* Briefly, the method was to subject the vinyl chloride to combustion with oxygen (explosion method using electrolytic gas to "energize" the combusiton), and absorption of the products of combustion. For mixtures containing insufficient oxygon for complete combustion, a known amount of additional air or pure oxygen was mixed with the sample before adding the electrolytic gas. A minimum amount of stopcock grease was used in the apparatus to reduce error through solubility of the gas. For the same reason rubber tubing was not used except for making joints of glass tubing, caution being taken to have the ends butt together. Tabld 1.--Symptoms produced in guinea pigs during exposure to vapors of vinyl chloride Type ot symptoms Concentration of vapor antj.period of .rpoauro prodnoin* 40 Propping to sides; incomplete n&roosla; nervous phenomena; irregular twitching of extremities................................ . IAUnpnMpstFaerAaednnintt e_us_ns_c_oo_nn_sfecieo-vt-u;-ms-m-ni-p-eo-os-tkos,;ruadiuteatexopira.antaarxcioas_i_s_; _ ___ 1 (10) ieaino twitching of extremities; quiet.............. Jerky, rapid respiration.................................. Slow.sbaltow respiration................................ Respirations ceased......................... * 1 * (10) 10-201 18 to 26 10 18-20 2 20 18-88 9 1 (900) 80 (>) 120-380 (380) 5 as * (3020) * (8850) 80 240 00 * (880) 880 380-880 '(380) ' * (880) 1.0 >(880) >(880) >(880) >(880) >(880) >(880) 0.8 >(m880i) >(880) *(880) >(880) *(880) 1 .N.o..t .dmetermminecdu.ring maximum ex_p.owswurseuupieurinotdoams gmivineunteins.parentheses. TEST PROCEDURE, DESCRIPTION AND CARE OF ANIMALS The test procedure, and the animals and their care were the same as described in the published report dealing with ethylene dichloride.' Concentrations of 10 to 25 per cent caused the animals to fall on their sides with convulsions and with jerky, rapid respirations in 1 to 2 minutes. Following this the pigs lapsed into a state of appar ently deep narcosis in which the convulsivo twitchings and all move ments ceased, the pigs being quiet and rolaxod. This occurred RESULTS OF TESTS within 16 to 20 minutes at concentrations of 15 to 25 per cent and The detailed test data are too voluminous to be presented in this within 60 minutes at concentrations of 10 per cent. Slow, shallow report and only summarized results pertinent to symptoms, gross ( respirations occurred with 20 minutes' exposure to 15 to 25 per cent pathology, and fatality are given. Specimens of tissue were taken for and with 120 to 360 minutes' exposure to 10 per cent. The pigs microscopic examination, a report of which will be made later. remained in this state until death or termination of the exposure. Concentrations of 5 and 2.5 per cent did not produce the initial > See previous footnote 6. See previous footnote 6. i Jones, Q. W., U. S, Sureau ot Mines, unpublished date. symptom of "dropping to their sides and unconsciousness with con vulsive twitching of the extremities." These concentrations pro duced first an unsteadiness in the animals, a staggering on attempt* eooceet'Z BFG36488 1966 4inuggutot 22m,1o9v30e about, with signs of motor ataxia. This occurred within 2 to 5 minutes, and lasted 50 to 90 minutes, at the end of which time the pigs fell on their sides in an apparent profound narcosis, being entirely relaxed with no convulsions or movements of any kind. The respirations were increased in rate and amplitude, becoming ---------- --------------------,--rrTTI , bo 40 60 70 1W TIME EXPOSURE. MINUTES LOG SCALE Fiauax 1.--Acute efleett of exposure of guinea pigs to vinyl chloride vapor In air rapid and jerky in character at the end of 240 minutes' exposure to 5 per cent, and slowed and became shallower at the end of 360 minutes, remaining in the latter condition until death or termination of the expCoosnurcee.ntrations of 0.5 and 1.0 per cent did not produce any 1967 Angus122, IStO The general symptom of narcosis was manifested in three degrees,1 increasing in1 severity with increasing concentrations of vinyl ohloride: (1) Unsteadiness, staggering, and motor ataxia; (2) incomplete narCo- sis in which convulsions affecting the trunk and extremities persist; (3) a state of profound or deep narcosis in which the animals are quiet,' on their sides, relaxed, and without movement. Observation showed that animals after being removed from the exposure chamber recovered from the most profound narcosis within 12 minutes. m No signs of eye or nasal irritation were observed. SYMPTOMS EXPERIENCED BY MEN I . 'I Two of the experimenters were exposed to 2.5 per cent vinyl chloride in air for a period of approximately three minutes. They reported that the gas had a fairly pleasant odor. They soon began to fed dizzy and disoriented as to space and size of surrounding objects, and complained' of a burning sensation in the soles of the feet. They immediately' recovered on leaving the chamber and complained only of a slight headache, which lasted about 30 minutes. '1 GROSS PATHOLOGY Control animals.--A total of 18 control animals were killed for' autopsy. No gross pathology resembling that found in the exposed' animals was found. Also no deaths occurred among the control animals. , Exposed animals.--The gross pathological changes found in the animals that died during exposure (see fig. 1 for conditions of exposure causing death on test) were intense congestion and edema of the lungs and a hyperemia of the kidneys and liver. The lungs were light pink in color; the cut section was uniformly light red, and bled freely,' A frothy exudate was present in the large bronchi, and squeezing of the lung tissue covered the cut surface with a frothy, bloody fluid.' The kidneys and liver were deep red to purple in color and the cut; sections were moist and dripped blood. The animals that died within 1 to 8 days following exposure showed' a congestion und edema of the lungs, with a swelling and hyperemia of tho kidneys. The findings in animals of these samo groups which' were killed for autopsy immediately after exposure showed a hyper emia and edema of the lungs, with a congestion of the liver and kidneys. Animals that were killed for autopsy 4 days following exposure still showed a hyperemia with areas of congestion through out tho lungs, whereas those killed for autopsy 8 days following exposure showed atelectatic and emphysematous patches throughout tho lungs. The findings in those animals that were killed immediately after exposure to conditions that did not cause death, but which caused August 22,1030 1968 a mild degreo of pathological change, were principally congestion and slight edema of the lungs, and hyperemia of the liver. The findings in the lungs were not as severe as noted in the exposures previously described. These changes cleared up in most of the animals within 8 days after exposure. A clouding and thickening of the cortex of the kidneys was noted in those animals killed-immediately after exposure to 25 per cent for 5 minutes and 5 per cent for 1 hour. This change was not noted in members of those groups killed 4 days and 8 days later. No significant gross pathological changes were found in animals exposed to 15 per cent for 10 minutes, 5 per cent for 30 minutes, and 2.5 per cent for 2 hours. DISCUSSION or PATHOLOGY Vinyl chloride is irritating to the lungs. Congestion and edema of the lungs are the most constant and prominent observations for exposure to conditions which caused death during or following expo sure. Accompanying the lung changes was a passive congestion of , the liver and kidneys. The signs of lung irritation which were found immediately after exposure to conditions which did not cause death, practically dis appeared within 8 days. A clouding and thickening of the cortex of the kidney was noted immediately after exposure to 25 per cent for 5 minutes and 5 per cent for 1 hour. These kidney changes were not present in animals of the same groups after 4 days. FATALITY AND SUMMARY OF PHYSIOLOGICAL RESPONSE A summary of the fatality and response of guinea pigs exposed to various concentrations of vinyl chloride in air is shown graphically in Figure 1, and given in conventional degrees of response in Table 2. < -The results of each experiment are designated by a symbol which represents one of six different degrees of severity. With the excep tion of concentrations causing death during exposure for which the results obtained for individual animals are given, the selected symbol describes the results obtained for at least one-half the individual ani mals, and in most cases the results are for the majority of a group (at least three and usually six animals) exposed to a given condition. It will be noted from the legend on Figure 1 that the six degrees of response are-- 1Died on test. 2. Majority died within 24 hours. 3. Majority died, 1 to 8 days. 4. Moderate injury, few deaths. 06P9t'Odg 5. Slightly injurious, no deaths. 6. Not injurious, no deaths. S00CC6P2 1969 In addition to representing the response of oaoh group by symbols, tho latter have been separated into four general fields or zones of. probable response, namely, 1. Probable death, 24 hours or less. 2. Serious response, occasional death. j 3. Without serious response. ( 4. Distinct symptoms. Table 2 gives the concentrations which produce the degrees of response generally reported in the literature dealing with noxious gases. These data may be compared with toxicological data for other compounds. * w * 1 2 3 4 * 6 7 8 Table 2.- -Acute effects of exposure of guinea frige to vinyl chloride in air Effect, of exposure after various period, of time 1. Kill, lo a vary short time......................... 2. Serious symptoms In a very short time___ 3. Moderate symptoms in a very short time. 4. Dangerous to life In 30 to 00 minutes.......... ......... t. Mnrked symptoms In 30 to eo minutes........................................... .............................. 6. Maximum amount for 60 minutes without serious disturbances leading to death.. 7. Maximum amount for 60 minutes without marked symptoms................ ................ 8. Maximum amount for several hours without serious disturbances______ ________ 0. Maximum amount for several hours with but slight or no symptoms..................... Concentra tion, par oeni by volume 70 to 40 , 10 it to* 10 S I tor LOtO 1.6; 0.6 L0 CAUSE OF DEATH DURING AND FOLLOWING EXPOSURE 1 The animals exposed to 20 to 40 per cent vinyl chloride entered a' state of profound narcosis which terminated in death. Recovery was rapid and without fatality following exposure for periods less than those causing death during exposure. This indicated that the degree of lung irritation acquired in these relatively short periods was insuf ficient to cause death. With concentrations in the range of 0 to 10 per cent the period between a profound but nonfatal narcose state and death was much longer! and permits considerable lung irritation to take place. Also, there was a probable action of vinyl chloride or products of its decomposition on tho liver and kidnoys. With 2.5 per cent, profound narcosis was present aftor 00 minutes and irritation of tho lungs occurred aftor several hours, but death was exceptional. mm gee previous footnotes 3, 4, 6,6. * Cotton, E. T., and Young, II. D.: The use of carbon dioxide to Increase the Insecticidal efficiency of fumigants. Proc. Entomological Soc. of Washington, vol. 31 (1920), pp. 97-103. 'Sayers, R. R., Yant, W. p., Thomas, B. O. II., and Berger, L. B.: Physiological response attending erposure to vapors of methyl bromide, methyl chloride, ethyl bromide, and ethyl chloride. Pub. Beelth Bui. No. 186 (1820), 66 pp. International Critical Tables, Arst edition (1037), vol. 2, p. 318. Also seo errata sheet, vol. 2. " Uenderson, Yandell, and Haggard, Howard W.: Noxious gases. American Chemical Society Mono graph No. 36, 1027. Chemical Catalogue Oo., Naw York. Attguit 22,1980 I 1970 HEALTH HAZARDS FROM VINYL CHLORIDE With regard to symptoms and pathology, as well as tho effecting concentrations, the response of guinea pigs to vinyl chloride appears to be similar to their response to ethyl chloride.* In equal concen trations and for single exposures, vinyl chloride is less harmful than gasoline, benzene, chloroform, and carbon tetrachloride. The comparatively harmless response to concentrations of vinyl chloride that will maintain a narcose state, together with its rather pleasant odor, suggests a possible use for producing surgical anaes thesia. This could be produced quickly by high concentrations and maintained with lower concentrations. Much additional work is necessary, however, to ascertain the practicability of its use. Vinyl chloride does not possess adequate warning properties of the odor or irritation type. With concentrations of 5 per cent or jess, Hit/ however, it gives warning by producing symptoms of dizziness and disorientation in advance of harm. With higher concentrations the narcotic action is very rapid and persons would have little time to heed the warning symptoms before holplossnoss would ensue. Vinyl chloride boils at less than ordinary room temperatures. As a rule, it is contained in cylinders under pressure. This is conducive to escape of the gas; on the other hand, the high concentrations re quired to produce physiological harm minimize the danger from leakage. There is, in fact, more danger from explosion than from harm to health from exposure. ACKNOWLEDGMENTS The writers desire to give acknowledgment to J. G. Davidson, manager of chemical sales for the corporation mentioned, and E. W. Reid, senior fellow of this firm's fellowship at the Mellon Institute, Pittsburgh, Pa., for sponsoring the investigation, to R. R. Sayers, chief surgeon, 'Bureau of Mines, for suggestions and advice, and to H. F. Brubach, laboratory assistant, Bureau of Mines, for assistance in performing the experimental work. BFG36491 SUMMARY AND CONCLUSIONS The acute physiological response of guinea pigs to air containing vinyl chloride was determined. The concentrations of vapor and periods of exposure ranged from those which produced death to those which caused no apparent effect after several hours' exposure. The symptoms, gross pathology, and fatality are given with a discussion of potential hazards. 1. The symptoms are principally those of narcosis. They range from unsteadiness and motor ataxia to incomplete and, finally, com- * See previous footnote 8. sooecepz 1971 AUffut 22,"l9lW r '* plete narcosis. The respirations vary from a rapid, jerky type accom-' panying the beginning of narcosis to a later, slow, shallow type. - 2. The principal gross pathological findings wore congestion and1 edema of the lungs, with hyperemia of the kidneys and liver. 3. Exposure to 20 to 40 per cent kills guinea pigs in a very shoft time; 10 per cent is dangerous to their lives after 30 to 60 minutes' exposure; and 0.5 per cent is the maximum allowable amount for. several hours without acute disturbances of a serious nature. 4. With regard to relative toxicity (concentrations causing acute harm), vinyl chloride is less harmful than carbon tetrachloride and chloroform, and is similar to ethyl chloride. 5. The danger from explosion exceeds the health hazard from exposure. \ 6. Vinyl chloride does not possess adequate warning properties, of the odor or irritation type. It gives warning, however, by produo* ing symptoms of dizziness and disorientation in advance of harm/ except when present in exceedingly high concentrations which would,' cause almost immediate helplessness and unconsciousness. 7. Tho narcotio action of vinyl chloride and its comparatively loir, toxicity suggest its possible use for surgical anaesthesia, ' . -------------- 'U / DEATH RATES IN A GROUP OF INSURED PERSONS Bates for Principal Causes of Death for June and First Six Months of 19>0 ilh The accompanying tables are taken from the Statistical Bulletin* for July, 1630, issued by the Metropolitan life Insurance Co. They present the mortality record of the industrial insurance department of the company for June, 1030, as compared with the preceding month and with the corresponding month of last year, and also give the rates, by white and colored policyholders, for the first six months of the years 1028,1929, and 1930, Death rates are given for the priatq cipal causes of death, and are based on a strength of approximately!) 10,000,000 insured persons. It should bo remembered that these rates apply to a more or less: selected group of persons. In recent years the general death rate for' this group has been approximately 73 per cent of the rate tor the'1 registration area of the United States. JUNE, 1930 ' The death rate for June among these persons was 8.3 per 1,000, the same as for June of last year, and the lowest rate for toe month' in the mortality records of the company. ' As compared with June of last year, improvement is noted for y diphtheria, influenza, tuberculosis, pneumonia, accidents, and homi* BFG36492 24333607-- ? C1k u & rt- 3 <* s ** < l6___ 1 1 l1 I* JZ3 v*> ex, a s fiauw &stet ^ o Jt * * *gtf S! n <9 2 * P c* " iMvMi5 c sa il3Il^^ o i 1i ! | |j j li:;| i 1!i 1i!il1!! l1!! !1Si