Document O311V945JQ8n0arKV6Bg7pYVp

* \ April 28. 1977 LEUKEMIA AMONG WORKERS EXPOSLO 10 ULHZLNL Peter F. Infante Robert A. Rinsky Joseph K. Wagoner and Ronald J. Young ^g' Industry-wide Studies Branch Division of Surveillance, Hazard Evaluations and Field Studies National Institute for Occupational Safety and Health Cincinnati, Ohio 45202 00378 -jL DO 06844? CONFTDFNTTAl YZ0000215 One of the earliest reports of benzcne-rolated hematologic disorders, which in consistent with wliat is now known to result from benzene poisoning was published in Paris in 1897.* By 1928, a clearly established cane of leukemia was associated with benzene o exposure in Italy. Since tliat time, numerous cases of leukemia among individuals having prior exposure to benzene have boon * reported,'in France, 3 in Italy, 4 in Switzerland, 5 in J.i|. m, (, m Turkey, 7 in the United States, 8 and in the Soviet Union. 9 A ` significant excess of dircrtoscmal aberrations also has been observed in benzene-exposed workers as conpared to controls.*0 Ishimaru, et al., have demonstrated a significant association between leukemia and occupations with probable exposure to benzene. 7 Aksoy et al., have reported a significantly greater incidence of leukemia among shoe workers exposed to benzene as contrasted with the incidence of leukemia in the general population. In 1976, Vigliani^ reported that 150 cases of leukemia attributed to benzene had been identified in Italy along. McMichacl et al.,** have demonstrated an I___ > excess of leukemia among rubber workers having had prior exposure to solvents including benzene. However, this study is subject to criticism because of exposure to a variety of solvents in the rubber products Jianufacturing industry. iI I ' V"V srr.rrvrjiri^v." no 068443 TOFNTTAl fONF YZ0000216 Parallel with tloosc observations of benzene-related hematologic disorders, production of benzene rapidly expanded. Approximately 10.2 billion pounds were produced in Uie U.S. in 1973, 3.5 billion pounds in Japan in 1972 and 1.2 billion pounds in the U.K. in 1972 12 Prior bo World Weir X, the major industrial use of lxmzenc was as a solvent in the rubber industry. During World War I, the demand for toluene in the manufacture of explosives greatly stimulated Ixinzen'* A t * . production. Itoday benzene is used principally as a cl iemic.il i.w $ material in the synthesis of caTpounds such as styrene phenol, cyclohexane, which accounts for 871 of its use. During the 50-year period following the first reported' benzene-associated leukemia, benzene has not been'widely acknowledged nor uniformly controlled as a carcinogen in the U.S. 13 --^ f Sue failure to control benzene as a carcinogen has resulted primarily from the reluctance of Industry and Goverjiment to accept the accumulated * case reports and epidemiologic observations as scientific evidence of the leukemogenic properties of benzene.' ltday, in the U.S. alone, an estimated two nu.lla.on workers have potential exposure ter benzene. 14 f For these reasons, the Industry-wide Studies Branch, National Institute for Occupational Safety and Health (NIOSII), undertook a study to determine mortality patterns among workers occupationally-exposed to benzene. Workers employed in the production of a natural rubber cast film (rubber hydrochloride, marketed under the trade name Pliofilm) at either of two localities in Ohio wore selected for- study. f - UV" DO 068444 OONF T OF NT T Al YZ0000217 t, 3- INDUSTRIAL IlYGIENfi ASSESSMENT 1'iouv .s^liurcripUon VM In the production of Pliofilm, natural rubter was masticated in an internal mixer (Banbury), passed throucjh a mill, and conveyed to mixing tanks wiiere benzene was added and the mixture was.agitated. Hie resulting solution was pumped to a blending tank. As the process continued, the solution was transferred into a reactor vr.MU'l, v U`i<' it was treated with HC1 to form rubber hydrochhn iiP*. At Hi is stage, additional benzene was added to adjust the percent of solids in the mixture. From the reactor vessels, the rubber hydrochloride was transferred to a neutralizing tank, vflicre Pliofilm scraps, soda ash, steam, plasticizers and additional benzene were added. After filtration, \ the rubber hydrochloride mixture was pumped to a castiny unit where the solution was spread on a continuous conveyor, the benzene was evaporated, j___ and the finished film was taken up on a roll, 'lhe gas containing benzene was exhausted from the casting unit, passed tlvrough a wet scrubber?""'' and channeled into an activated charooal absorber unit, wJiere benzene was recovered and recycled. Hie rolls of Pliofilm were transferred to another room where they were inspected for quality, trirrmod, cut to customer specification and packed for subsequent usage primarily for food wrapping. Jn the production of Pliofilm, the only material known to associated with Ixaiolologie diforders was benzene. OU>cr materials usod in the process included hydrochloric acid (J1C1), soda ash and snail [ amounts of anlioxidants and plasticizers. Hie mmufacturing process .- i Is*. > 00 068445 00NFTDFNTIA1. YZ0000218 was essentially identical at )x>Lh locations. l-'nyji i. iiml.iil tv.*nitaring In 1942, a inomlcr of corporate managenent recamcnded as a policy for the rubber industry, vduch wuld include Pliofilm operations, periodic '.air monitoring and a complete blood count for all1 new employees1. 5 Furthermore, Wilson slated "a closed system of- ventilatim- vdiere the workman ootres in contact with no fumes .is ideal. An/ other type of ventilation is not entirely safe." Shortly thereafter, extensive l* exhaust-ventilation equipnent was known to have been installed in the Pliofilm department located in St. Mary's, Ohio. The Industrial Carmission of Ohio (ICO) surveyed the department in 1946 and stated: "Tests were made with benzol detectors and the results indicate that pwr; concentrations have been reduced to a sale .level and in most instances. range from zero to 10 or 15 ports per million" (ICO report, Nov. 1946). A ------ further investigation of benzene exposure at this facility in 1956 concluded that exhaust ventilation controls were of excellent design i r (100 report, Jan. 1956). In the early 1960's, benzene point-source concentrations were measured by company personnel using detector tubes. A total of 112 surveys were conducted at tins facility over the 11 year period, 1963-1974. 'll lose and earlier surveys have indicated that employees? benzene exposure was generally below the reccmncnded concentration in effect at the time of each survey5ee Table 1. j L_ w r. DO 0B8446 OONFTDFNTTAl YZ0000219 llirtoriccil environmental data for the seoond facility is less well defined. However, based on walk-through observations, discussions \Z< with carpany personnel, and the meager environmental data that was retained, we arc convinced that employee's benzene exposure at the seoorvd faciJity was consistently well-within the reoctmruxlod limits. Methods ' ltotrospective Cohort Study n All white males having had direct exposure to benzene at any time 1 during the period of January 1, 1940 through December 31, 1949 were selected for study. In each plant, the departments and jobs involving direct exposure to benzene were determined following a walk-through fnr survey by NIOSH personnel which included a review of the PMofiJm process, of engineering controls and of available air sanpling data. ; I Ocmpany personnel also assisted in these determinations. Job classificatioi with benzene exposure were determined without knowledge of the workers vital status. n Follow-up of all study cohort members was attempted from the time of termination of employment to June 30, 1975. lb date, vital status determination has been made for approximately 75% of the 748 cohort members. Persons for whom which vital status could not be determined were assumed to be alive so as not to overestimate the true risk of lynpJiatic and hematopoietic malignancies associated with benzene exposure. J /***>? ' * T. - 1Z h/ .. ^a v 00 068447 OONFTDFNTTAl I YZ0000220 % -6- Causcr. of death were determined frcm death certificate reporting and were coded by a qualified nosologist using (die International Classificatic of Diseases {1CD codes) in effect at the time of death; these codes were then converted to 7th Revision numbers. A modified life-table technic was usod to generate person-years at risk of dying according to five-year age group and five-year calendar time periods. Person-years of observation and causes of death v.> io I<jLcmined for the time period January 1, 1950 through June 30, 1975, the period of observations for risk of dying. Person-years of observation and deaths occurring prior to January 1, 1.950 were excluded frcm the data analyses since vital statistics on lymphatic and hematopoietic malignancies were not publishod prior to that dule. 'iwo populations were chosen as control groups generating the numbers of expected deaths in the study population. The first group consisted of the U.S. white male general population specific for age and calendar time period. The second group oonsistod of 1447 white males who were initially employed in the State of Ohio at a fibrous glass construction products facility between January 1, 1940 and December 31,. 1949 and wlx> had achieved five or more years of employment by June 1, 1972, which was the cut-off date for vital status ascertainment in Die fibrous glass control population. 19 "Jr_ ?* vrrrr?; .r^rri-w n 48 C0^tdfn T M( ` .. .n *_ YZ0000221 -7- RMUlUf! * V'. As tdxjwn in Table 2, 140 deaths from all causes wire observed oneny benzene .exposed workers as contrasted v/ith 187.6 existed deaths. Ibis deficit is partially a reflection of incomplete follow- up of the study population at the tine,of this report:, Table 2 also shows a significant excess of deaths freni malignancy it-*' lynphatic and henutopoietic system (200-205) wlu n rxiiiui ud to that expected on the basis of U.S. white rule rates. This is a reflection of excessive deaths frem leukemia (204). To date, seven leukemia deaths have been observed versus 1.38 expected (p<0.002) based on U.S. white male rates and 1.48 expected (p<0.002) based on rates for fibrous glass workers, ivnn mnro striking is thu observation that *Ctr \ all seven leukemia deaths were from either of the myelogenous or monocytic type. Data for type, age at death arid interval since initial exposure to benzene arc shown in Table 3. The period between initial exposure and death ranged from 2 to 21 years. These hidden observations indicating a specific type of leukemia are highly consistent with the data of Viliani * which show a predominance of tlx acute myelogenous I leukemia among workers exposed to benzene in the rotogravure and shoe-manufacturing industries in Italy. Since data for specific types of leukemia mortality in the U.S. are not readily available for the study period, incidence rates for myeloid, monocytic leukemia and total leukemia Iran the Connecticut Tunor Keyistry2'0 for tie period 1960-1962 were applied to the age distribution of the benzene exposed cohort to I*' generate the sjoci.fic proportion of total leukania cases wliich would be i DO 0f>H4 4D CONFTDFNTT Ai i| YZ0000222 -B- of the myelaionocytic typos. Of the total expected number of incidence case:; of leukemia, 50.37% were calculated to bo of the mylomonocytic vV. types, This proportion was applied to the total nurrber of expected leukemia deatlis in the study cchort winch had been previously generated cn the basis of U.S. wliitc male population rates. The results indicated an expectation of 0.0967 (0.5037 x 1.3831 = 0.6907) deatlis fjron iiyoUn and monocytic leukemia as oaiiparcd to seven observed; lJ*Nil* Uujvj 1004. i Thus, Pliofilm workers exposed to benzene can be estimated to be at a . I 10-fold increased risk of dying from myelaionocytic leukemia. As a result of past failure to control benzene as a carcinogen, millions of workers, without knowledge of the hematopoietic dangers, arc continually being exposed to benzene in tho occupational setting. In addition, unknown liixibors Of CuuSumjxs, including children, are exposed to benzene through use of products around the hare such as model airplane glue, and paint strippers (sane containing up to 50% benzene). It is now hoped that the current findings which demonstrate overwhelmingly an increased risk of leukemia in workers exposed to benzene will stimulate efforts to control occupational and oonsuner exposure to benzene, an agent known for almost a century to be a 4 powerful bone marrow poison. L DO 068450 CONFTDFNTTAl YZ0000223 Itm-MvNCI-S js '. 1. ' LeNoir, Claude. Cor un ens do purj>ura nttribuc a 11 intoxication par la benzine:i Hull. Mean. Soc. Mod. Hop. 1097, 3, 1251. 2. r., jurgnirvino, C. Leuccmic, aigue nu cours do 1'intoxication I*i*i**. Cue 1'oriejino loxicjuc do carlaincr; lcucauicB aiyuos ct lours relations avec los anemies graves, J. Med. Lyon. 1928, 9, 227. 3. Cocpicl, A., Caviejneaux, A., Bernard, J. Jos lcuccmies licnzcni.ques de la region Parisionne entree 1950 ct 1965 (etude de 50 observations), Nouv. Rev.. Franc. llcnut. 1967, 4, 465. 4. Vigliani, 13.C. Leukemia associated with benzene exposure, Ann. H.Y. Acad. Sci. 1976, 271, 143. 5. Ludwig, \MJ., Wcrlhemann, A. Benzol-Myelopathica, fVhwv... ;i.d. Wsdir. 1962, 92,378. i 6. Isiiimaru, T., Okada, II., Itxniyasu, T., Tsuchimoto, T., Hoshino, T., Ichina.ru, M. Occupational factors in the epidemiology of leukemia in Hiroshima and Nagasaki, Arner. J.'Epid. 1971, 93, 157. 7. Aksoy, M., F.rdem, S., DinOol, G. Leukemia in shoe-workers exposed chronically to benzene, Blood. 1974, 44, 837. 8. Mallory, t.h. , t-n I .i, k,a., Brick ley. w. J. Chronic exposure to benzene (benzol). 111. 'Hie pathologic results, J. industr. Ilyg. Jtxiool. 1939, 21, 355. 9. Tareeff, E.M., Kontchalovskaya, N.M., Zorina, L.A. Benzene leukemias, Acta. Un. Int. Cancer. 1963, 19, 751. 10. Ftomi, A., Pncifico, E., J,imantn, A, Chranosane studies in workers exposed to benzene or toluene or both, Arch. Environ. Health. 1971, 22, 373. 11. McMichaol, A.J. , Spirtas, It., Kupper, L.L., Gantole, J.P. Solvent exposure and leukemia among rubber workers: an epidemiolgic study, J. Occup. Med. 1975, 17, 234. 12. IAHC Monograplis on the evaluation of carcinogenic risk of chemicals to nun. Some anti-thyroid and related substances, nitrofurans and industrial clicmicals. 1974, 7, 203. 13. Code of Federal Regulations, Title 29: -Subtitle H, Diopter XVII, Occupaional Safety and Health Administration. Part 1910. 93, U.S, Govern;nent Printing Office, Washington. 1971. .V !4 F} s r -- -mrtWLML. On O-OMp 6845i YZ0000224 14 . Criteria for a rcoonmcndod standard. Occuitionnl exposure to i<*. II.P. Dept. Health, Educaion and Welfare, Public Health Service. 19/4. -1 .= 15. Wilson, R.H. Benzene poisoning in industry. J. Lab. Clin. Mod. 1942, 27 ,'1517; 16. Drinker, P. Criteria of industrial health hazards. In United States Department of labor: Protecting Plant Manpower. Washington, U.S. Government Printing Office. 1941.- 17. Sappington, C.O.: Essentials of Industrial health. Phi 1. I M|*hl,i, J. D. Wppinoott Co., 1943. ! 18. USA Standard Acceptable Concentrations of Benzene, 237.4. New York: ' Unitod States of America Standards Institute, Inc. 1969. 19. Bayliss, D.L., Dement., J.M., Wagoner, J.K., Blcjer, II.P. Mortality patterns among fibrous glass production workers, Ann. N.Y. Acad. Sci. 1976, 271, 324. 20. Cancer in Coiinocticut, Incidence and Bates, 1935-1962. Connecticut State Dept, of Health, Hartford, Connecticut. 1966. W*~ | **int*- ^ C* ' i DO 00845? OONFTOFNTT Al *s a** - YZ0000225 TABLE 1 aii.tiu)/xTY or w-mwi-iNDKo nKNsmn ccuciimiATioNS IN 71IE WORKPLACE IN 71IE UNITED STATES Year 1941 1947 i 1940 1957 1963 1969 1971 ' `Standard, pjrm 100 MAC 50 B-hr. 7WA 35 8-lir, 1W 25 B-hr. 7WA 25 Ceiling 10 B-hr. TWA 10 8-hr. 7VIA * `Reference 16,17 J4 14 14 14 18 13 tMte ,VV i i *i i i MAC Maximum Allowable Concentration TWA ** Time Weighted Average fi '$**CyrT\x:: L Do 068453 OONFTDFNTTa: YZ0000226 TABLE 2 Status on April 13, 1977, of Observed Deaths from Specific Causes Among White Holes Between 1/1/60 and 6/30/75 Who Were Exposed to Benzene and Employed Sometime Between 1/1/40 and 12/31/49, as Contrasted With Exprriori Deaths Based on Both the U.S. While Hale Population (USWM) iind on an Industrial Population Exposed to Fibrous Glass (FG). Benzene Exposed Workers Causes t of death (1CD codes) Deaths Observed Deaths Expected Comparison fa nop Mill --" All causes (200-205) (204) (200-205) (204) 140 9 7 9 7 187.5809 3.4497 . 1.3831 ` 5.1020 1.4758 (USWM) (USWM) (USWM) (FG) (FG) 075 260+ ^ 506++ .... 176 * \ 474++ | t ICD 7th Revision Codes (200-205) = Total Lymphatic and Hematopoietic Cancer; (204) = Leukemia only + p<0.05. ++ p<0.002 SMR * OBS./EXP. x 100 Infante, Rinsky, Wagoner and Young, 1977. r L~ i L DO 068454 OONFTOFNTT Al YZ0000227 4 TABLE 3 CASES OF LEUKEMIA AMONG WORKERS EXPOSED TO BENZENE DURING 1UE MANUFACTURE OF PLIOFILM Case Number ; i 1 2 3 n 5 6 7 8* Type of Leukemia Age at Death (years) Acute myelocytic Acute myelocytic Acute myelocytic Acute myelocytic Monocytic Chronic myelocytic Monocytic Myelocytic 60 65 62 57 57 29 36 28 Period Between Initial F and Dt'.iMi (><MI ',) 13 10 21 19 15 2 17 3 ' .r i " l_ r, pc- ii% i_t f * Indicates leukemia case which did not fit into cohort definilion. The subject began employment in 1950. Infante, Rinsky, Wagoner and Young, 1977. c * vs,f . I YZ0000228