Document Y2qVR8DOy46b27kKymK6oEQE

Recommendation ------ for an Occupational Exposure Standard fdb Benzene , The National Institute for Occupational Safety and Health (NIOSH) recommended on August 25,1976 that occupational exposure be controlled so that no worker will be exposed to benzene in excess of 1 ppm (3.2 m^/m3) in air as determined by a 2-hour air sample col lected at 1 liter per minute. Previously, in a criteria document transmitted July 24. 1974, to the Occupational Safety and Health Admin istration (OSHA) in the Department of Labor, NIOSH recommended adherence to the pres ent Federal standard of 10 ppm as a timeweighted average with a ceiling of 25 ppm (but without the permitted excursion to 50 ppm as in the existing standard). At that time. NIOSH, recognizing that there were data sug gesting a relationship between exposure to benzene and the occurrence of leukemia and other malignant diseases among employees at risk of such exposure, expressed the need for detailed, comprehensive epidemiologic investi gations of the long-term relationships of mor bidity and mortality due to leukemia and other malignancies in the population at large and that of workers with benzene. The recommen dation for a more stringent standard was made after review of evidence subsequently accumu lated from clinical as well as additional epi demiological data indicating that benzene is leukemogenic. Because it causes progressive malignant disease of the blood-forming organs, NIOSH recommends that for regulatory pur poses, benzene shall be considered to be car cinogenic in man. An issue of particular concern is the pres ence of benzene in gasoline and its impact, particularly in gasoline station operations. Recent information indicated that service sta tion attendant exposures were less than 10 ppm total gasoline vapors and that if United States gasolines remain at about 1 percent by volume of benzene, exposure levels to ben zene will probably stay below 1 ppm, Future efforts to reduce evaporative losses at gasoline stations under EPA regulations should help to* further decrease exposure to benzene at such. facilities. Emphasis should be placed on pro hibiting the occupational use of benzene as solvent or diluent in open-type operations^. Furthermore, product substitution should b; OEC 1 a paramount consideration wherever benzen > is identified or its presence suspected, espe\ cialiy with concurrent indications of alterations' in the blood or the hematopoietic system, it should be replaced with less harmful substi tutes wherever feasible. '7 7 Because it' is not possible at present to establish a safe exposure level for a carcin ogen, the NIOSH recommendation is to restrict exposure to very low levels that can still be reliably measured in the workplace. The NIOSH recommendation can be expected, at a minimum, to materially reduce the risk of benzene-induced leukemia, The recommended standard is readily measurable by techniques that are valid, reproducible, and available to industry and Government agencies. In addition tc possibly causing leukemia, exposure to benzene can result in central ner vous system depression and skin irritation. Com pliance with all sections of the NIOSH recom menced standard should prevent noncarcinogenic adverse effects of inhalation or dermal exposure to benzene in the workplace. NIOSH estimates that 2 million workers are poten tially exposed to benzene in printing, lithog raphy, and dry cleaning, and in the manufac ture of coke and gas, adhesives, coatings, and a variety of chemicals. The proposed standard would apply to the processing, manufacture, and use of benzene and benzene products covered by the Occupational Safely and Health Act. ^ ?: " *7? S*. si tt p. nrr* .jv : ; . ! : ms. U.S. DEPAR.TTMMEENfJT OF HEALTH, Et>UCjft.TXOf>f,'AN$ W EfcL?FFARE Public Hesaalth Service " '' '** 1 " -v t iij Center for Disease Cohtrof' National Institutofoi(Occupational Safety VndiH&ifth A >' I * ? ft SbK] Aocrtonal copies a*e from: Nation* iniiituM for Occupational Safety and Health 4S74 COLUMBIA PAfcKVSAY CINCINNATI OHIO 40226 Plsaas include a teif-addrmtd man* mg label to aiilftt In amwer.ng your request. 00908 DO 068468 CONFTDFNTTA1 YZ0012149 Recommended ^jpndard UPDATE CRITERIA AND RECOMMENDATIONS FOR A REVISED BENZENE STANDARD AUGUST 1976 In 1974, the National Institute for Occu pational Safety and Health (NIOSH) issued criteria and recommendations for a standard for occupational exposure to benzene [1], A cause-and-effect relationship between benzene and observed blood abnormalities, especially aplastic anemia, was recognized. At that time, NIOSH, recognizing that there were data sug gesting a relationship between exposure to benzene and the occurrence of leukemia among employees at risk of such exposure, expressed its need for detailed comprehensive epidemiologic investigations of the long-term relationships of morbidity and mortality due to leukemia and ether malignancies in the population at large and in those who work with benzene. Between 1974 and mid-1976, seven epi demiologic studies have been reported [2-8] along with case reports of benzene-related blood dyscrasias 19-11] and chromosomal aberrations {ll-l-ti. Although some investi gators have observed only acute forms of ben zene-associated leukemias [9-12], a recent connection with chronic leukemias has been noted [3,4,13], Reports prior to 1974 of chronic myelocytic or lymphocytic leukemia [15-18] and erychrcieukemia [19-23] are not as numerous, as tne observations cf acute myelocytic cr lymphocytic types [16,17,24-26). Because of the rarity of erythroleukemia, Vigliani and Forni [12] regard as significant the three cases which they have observed. Be cause case records accumulated by one in vestigative group [12] of patients with acute or subacute leukemia have become so num erous in the past two decades, many cases formerly diagnosed as acute pancytopenia are now considered to be examples of acute leu kemia. In 1974, McMichael et al [3] reported on the first phase of a study of a population at risk comprised of active and retired employees of a major tire-manufacturing plant in Akron, Ohio. A cohort of 6,678 male rubber workers was followed for 9 years {1964 through 1972), and data on 1,783 deaths were obtained. Comparison with the 1968 US national mor tality data yielded a Standardized Mortality Ratio (SMR) in the U.S. male population of 99 from all causes of death for the full cohort and of 93 for an active employment subcohort in the age range of 40 to 64. Among other find ings of cause-specific deaths, the highest SMR's were for deaths from causes related to the hematopoietic and lymphatic systems. The SMR showed an excess mortality of ap proximately 2-2.5 and was higher for the "active" age range (40-64) than for the full age range (40-84). For leukemia deaths in the 40-64 age range, the SMR was 315--approx imately a threefold excess. It was recognized that, because no distinction was made in this evaluation between different groups of work ers having different work experiences, a "di lution effect" could occur. A second phase of the study [4,6] compared different groups of rubber workers. McMichael et al [3] stated that, from this initial study alone, it should not be assumed that the observed cause-specific mortality excesses were attributable to workenvironment exposure within the rubber in dustry. Such excesses could have been a spur ious association such as a "selected" popula tion in which all persons living in Akron might have been exposed to some specific unknown factor. Similar findings from 5 other plants in widely differing parts of the US, however, make this explanation unlikely, in the opinion of the authors. Pending completion of the second phase of the study, the authors concluded that they could only suspect, rather than con clude with confidence, that working in certain jobs within the rubber industry entails an in creased risk of dying from these specific causes. In a followup of the same cohort [3], Me- DO 06R469 CONFTDFNTTAI YZ0012150 Recommended S^ftndard Michael et al (4) in 1975 extended the epi demiologic study to indicate an association between leukemia and jobs entailing exposure to solvents among which benzene was once the solvent of choice. After noting that leu kemias in general demonstrated a threefold excess in mortality in the 40-64 age range, and with further subclassification of the In ternational Classification of Diseases categor ies to identify specific leukemias, a sevenfold excess of deaths from lymphatic leukemia in the 40-64 age range was observed. Six of eight deaths were from chronic lymphatic leu kemia. Myeloid leukemia was the next highest category in this age range, showing a twofold excess. At smaller plants not located in Ak ron, Ohio, a complete study was not performed for reasons of cost and time; nevertheless, a proportional mortality analysis demonstrated a 45% excess of leukemia. The question of whether the observed mortality excesses were associated with specific job categories within the rubber industry was then investigated. Nineteen of 70 occupational titles were asso ciated with solvent exposure and were grouped as heavy, medium, and light solvent exposure. A discriminant function analysis based on time spent in various work groups and Inde pendent of the previously observed mortality excess revealed a statistically significant posi tive association between solvent exposure and lymphatic leukemia. One job title within the 3 solvent-exposure groups, tire repair, showed a sixfold difference between cases and con trols in a comparative test of relative risk of lymphatic leukemia. It was pointed out that tire repair involves considerable swabbing of tires with solvent, and, at some time in the past, the solvent predominantly used was ben zene, Because each of the 4 cases observed had started working at the plant at some time since 1945, it was suggested that the leukemogenic agent may be a chemical that had been present in recent decades and may still be present. Finally, it was of interest to the authors [4j that it was lymphatic rather than myeloid leukemia that appeared to be asso ciated with solvent-exposure jobs. A third study by McMichael et al [6] in 1976 involving the same cohort of rubber workers previously reported [3,4] indicated that mortality from lymphatic leukemia was also very strongly associated with working in the synthetic plant, a place where NIOSH has been unable to identify benzene-related ex? posures. The synthetic plant is essentially a chemical plant making important syntheticrubber intermediate products, such as styrenebutadiene and neoprene. An unexpected asso ciation of lymphatic leukemia with the janitor* ing-trucking occupational title group was ex plained by speculating that the transfer of workers to this group occurred for medical reasons, especially where conditions were not rapidly fatal and for which active employment could be maintained while in apparent disease remission or stabilization. Andjelkovic et al |5], studying the same cohort as McMichael et al [3,4,6], distinguished between active worker mortality experience and retired worker mortality experience, particularly in workers who retired before age 65. Results were es sentially the same as previously reported [3,4,6] with findings of excess mortality for both active and retired workers from neo plasms of the lymphatic and hematopoietic tissues. In addition, the expectation was con firmed that workers who retired prior to the normal retirement age of 65 would have a less favorable mortality [experience] than active workers of the same age range; however, the magnitude of the excess, an SMR of 202 as compared with 61 for the active workers, was unexpected (p less than 0.001). Monson and Nakano [7] in 1976 reported another mortality study in a cohort of 13,571 white male rubber workers, again in Akron, Ohio. From the records of 5,079 deceased employees, excess deaths from leukemia oc curred most often among workers in the tire (18 observed 11.7 expected) and in the pro cessing (10 4.2) divisions. Excesses were also seen among workers in the chemical di vision (2 0.7), in elevator areas and cleaning (3 0.4), in shops (7 6.6), and in industrial products (9 7.0). Benzene was reported to have been used extensively in the industry. While pure benzene was no longer used as a solvent, it was stated tc be a contaminant in many of the solvents still used [7J. In a mortality study of 20,163 petroleum- DO 068470 OONFTDFNTTAI YZ0012151 refinery workers carried out in 17 refineries [8], mortality from lymphomas was reported to be greater than expected, though not sta tistically significant, in 3 categorized exposure groups listed as high exposure (laboratory, maintenance, and salvage-recovery jobs), low exposure (plant security, utility, purchasing, and motor transport jobs), and medium ex posure (all other jobs). A suggestion was made of increased mortality with increased exposure. No mention was made of benzene exposure. In an epidemiologic survey of leu kemia reported by Thorpe (2) in workers in a variety of petroleum and petrochemical oper ations, a number of problems of data collection were experienced. The incidence of benzeneassociated leukemia was not considered to be abnormal compared to that of the general population in the countries concerned. Em phasis was placed on the need for improve ment in the recording and storage of biologic observations, job histories, occupational ex posures, and demographic data. A 1971 report by Ishimaru et al (27) de serves to be mentioned here because it spe cifically associates benzene or its derivatives and medical X-rays with an approximately 2.5 times excess risk of leukemia in workers. Ishimaru et al [27] organized 15 groupings based on occupational categories reportedly listed by Milby et al [28] as workers who handle benzene or are exposed to medical X-rays. Four categories were not included in the reported results because the authors found no leukemia in either test or control workers with such occupational histories as litho graphers, painters, and laboratory technicians; yet, these workers might well be expected to experience benzene exposure because of the known presence of benzene in such occupa tions. Many of the selected occupations such as carbon dioxide-gas furnace workers, tin smiths, sheetmetal workers, soft drink-manu facturing workers, and barbers 'were not listed by Milby et al; furthermore, those occupations would not likely have benzene exposure. In addition, no investigation was made of the specific chemical agents handled by the in dividuals engaged in the selected occupations and the identified cases of leukemia in both the test and the'control groups were generally low, mostly numbering only 1 or 2. Occupa tions where a high association with benzene exposure would be expected, suen as leather products workers and workers engaged in printing, repairing, or cleaning of printing machines, showed no excess whereas welders, platers, tinsmiths, or sheetmetal workers dem onstrated an excess of leukemia where exten sive use of benzene would be questionable. This study [27] Is not considered to be suffi ciently definitive to conclude that a relative risk of leukemia from probable occupational exposure to benzene or Its derivatives exists. Animal experiments designed to investi gate the carcinogenic action of benzene have failed to give reliable information on its ca pacity to produce an increased incidence of leukemias [29], Lignac [30] in 1932 claimed to have produced six cases of leukemia and two cases of lymphosarcoma in a strain of white mice given 0.001 ml benzene in olive oil once a week by subcutaneous injection for up to 11 months. Attempts to repeat these observations have yielded equivocal results [31-34]. A high tumor incidence often mani fested as leukemias in untreated mice has been found to be caused by certain virus strains, it has therefore been considered quite conceivable that leukemias described in the earlier experiments in mice after ben zene treatment have, in large part, developed spontaneously or by virus infection, rather than being caused by benzene [29], The literature is replete with medical case reports of leukemia directly associated with occupational exposure to benzene. These leu kemias have occurred throughout the indus trial world, most frequently as a result of using benzene in solvent applications. In France, Goguel et al [17] in 1967 described 50 in stances of leukemia, of which six had already been reported, in the Paris region from 1950 to 1965. The 44 new cases included 13 chronic myelocytic leukemias. 8 chronic lym phocytic leukemias, and 23 acute leukemias. Frequent disturbances cf the erythrocytes and their precursors were noted. Girard and Revci [16] added four observations of acute myeloid leukemia and nine cases of chronic lympho cytic leukemia m 1970. In tne Soviet Union, no OAR471 CONFTDFNTTAl YZ0012152 ^Pecommenc/ed Stgpdard j Tareeff et al [18] found 6 acute and 10 chronic zene, the appearance of a virus in exposed cases of leukemia among what were described human beings, and the occurrence of acute as printers, primers, apparatus men, and leukemia in these people would strongly sup chemists. In papers published mostly through port such a hypothesis. the 1970's. Aksoy and coworkers [9,10,24, 35-39] in Turkey have identified more than 50 patients with aplastic anemia and 34 cases of leukemia, all in workers having chronic ex posure to benzene. These included one case of erythrocytic leukemia, three cases having a possible genetic predisposition, and one It is apparent from the literature that socalled benzene leukemia continues to be re ported. The inadequacies in correlating ex posure-effect relationships were discussed by NIOSH in 1974 [1] and studies subsequent to 1974 which would aid in evaluating the con- case of chronic myelocytic leukemia. In addi tion, a suggested relationship between Hodg kin's disease and chronic benzene exposure was reported. In Italy, 34 fatal cases of ben zene-associated aplastic anemia and leukemia have been observed [12]. Data from the In sequences of exposures to various airborne rnnr^fo'jjnpic nf hpnrne fjave not been Toynd in the literature. Case records of pa tients with acute or subacute leukemia have become so numerous that, according to Vig liani and Forni [12], they exceed those of stitute of Occupational Health of Pavia, Italy, indicate that, of 16 deaths occurring between 1960 and 1974 among 142 workers identified with chronic benzene poisoning, only 3 died of acute pancytopenia, a fact which has led to the belief that many cases previously con sidered as pancytopenia may indeed have been examples of hemocytoblastic leukopenic and aplastic anemia and 13 died of leukemia [12]. The observations of at least 20 cases of acute aleukemic leukemia. In spite of the diversity of chemicals to which workers are frequently erythroleukemia in the literature is considered to be significant [12] because of the rarity of the disease. Vigliani and Saita [40] in 1964 exposed, both singly and in mixtures, the de velopment of blood abnormalities can, for the most part, be linked with exposures to ben calculated that, for workers heavily exposed zene. Data are lacking to support the sugges to benzene in the provinces of Milan and tion by Girard and Revol [16] that homologues i Pavia, the risk of acute leukemia was at least of benzene might be leukemogenic. Viglianj 20 times that of the general adult population. and Forni [12] observed that since the re Cases of benzene-associated leukemia have placement of benzene ~with toluene as a sol- also been reported in Spain (20), Scandinavia vent in the rotogravure industry in 1964. no [22], and the United States [13.25]. new .cases of aplastic anemia pr of leukemia due to toluene exposure have been seen. Fur The consistent observations of chromo thermore, workers have not shown the chromo somal aberrations associated with benzene ex posure continue to be reported [13,41,42]. some aberrations frequently seen in workers exposed to benzene. The statement by Ger- The implications of the chromosome findings with respect to benzene leukemia are still not arde [46] that benzene is unique among hy drocarbons in its myelotoxic potency seems as clear. The possibility of a chromosomal in volid today as in 1960 when it was made. The stability acting as a stimulus for a latent leu- excess risk of leukemia recently reported in kemogenic virus has been speculated upon [12]. the rubber industry by separate investigative groups [3-7] is considered by NIOSH to be The recently reported isolation of a com plete human RNA tumor virus (Type C) asso ciated with acute myelocytic leukemia [43,44] indicative of probable benzene exposure, espe cially since benzene was at one time the agent of choice for many solvent operations. raises again the possibility that a chemical carcinogen activates a latent leukemogenic virus in accord with the generalized suggestion of Todaro and Huebner [45], The demonstra tion of a relation between exposure to ben- .NIOSH considers the accumulated evi dence from clinical as well as trom epidemifl-~ Togic data to be conclusive at this time that .Be'nzeneJa.leukftrnngEaic. Because it causes progressive, malignant disease of the blood- DO 0AR47? CONFTDFNTTAl YZ0012153 iiisass^ Recommended fyandard forming organs, NIOSH recommends that, for regulatory purposes, benzene be considered carcinogenic in man. in view of this conclu sion and since it is not possible at this time to establish an exposure level at which ben zene may be regarded to be without danger, NIOSH recommends that exposure to benzene be kept as low as possible. The use of ben zene as a solvent or diluent in open operations should be prohibited. Furthermore, product substitution should be a paramount considera tion. Wherever benzene is identified or its presence suspected, especially with concur rent indications of alterations in the blood or the hematopoietic system, it should be re placed with les,s harmful substitutes wherever feasible. The sampling and analytical method for benzene in air recommended by NIOSH [1] employs adsorption on charcoal followed by desorption and gas chromatographic measure ment. Personal sampling pumps operating at approximately 1 liter/minute, for a 10-minute sample at a mean concentration of 22.8 ppm, collected a quantity of benzene that, upon analysis, yielded a relative standard deviation (precision) of 11.6% [1). Results from collab orative testing indicate that sampling at 1 liter/minute for 2 hours will collect a suffi cient quantity of benzene from an airborne concentrations of 1 ppm to allow a relative standard deviation in the range of that pre viously reported Jl], which is considered ac ceptable. One ppm represents the lowest level at which a reliable estimate of occupational exposure to benzene can be determined at this time, in consideration of the limitations of biologic and air measurement technics. NIOSH recommends that occupational exposure be controlled so that no worker will be exposed to benzene in excess of 1 ppm (3.2 mg/cubic meter) in air as determined by an air sample collected at 1 liter'minute for 2 hours. REFERENCES 1. Criteria for a Recommended Standard___ Occu pational Exposure to Benzene. US Dept, of Health, Education, and Welfare, Public Health Service, Center for Disease Control, National In stitute for Occupational Safety and Health, 1974. 2. Thorpe JJ: Epidemiologic survey of leukemia in persons potentially exposed to benzene. J Occup Med 16: 375-82. 1974. 3. McMichael AJ, Spirtas R, Kupper LL: Art epi demiologic study of mortality within a cohort of rubber workers, 1964-72. J Occup Med 16:458-64, 1974. 4. McMichael AJ. Spirtas R, Kupper LL, Gambia JF: Solvent exposure and leukemia among rubber workers--An epidemiologic study. J Occup Med 17:234-39, 1975. 5. Andjetkovlc D, Taulbee J, Symons M: Mortality experience of a cohort of rubber workers, 19641973. J Occup Med 18-:387-94, 1976. 6. McMichael AJ, Spirtas R, Gamble JF, Tousey PM: Mortality among rubber workers--Relationship to specific jobs. J Occup Med 18:178-85, 1976. 7. Monson R, Nakano KK: Mortality among rubber workers--I. White male union employees in Ak ron, Ohio. Am J Epidemiol 103:284-96, 1976. 8. A mortality study of petroleum refinery workers, Medical Research Report #EA 7402. Washington, DC, The American Petroleum Institute, 1974, 41 PP 9. Aksoy M, Erdem S, Dincol G: Leukemia In shoeworkers exposed chronically to benzene. Blood 44:837-41, 1974. 10. Aksoy M, Erdem S, Dincol G: Types of leukemia in chronic benzene poisoning. A study in thirtyfour patients. Acta Haematol (Basel) 55:65-72, 1976. 11. Vigliani EC: Leukemia associated with benzene exposure. Ann NY Acad Sci 271:143-51, 1976. 12. Vigliani EC, Forni A: Ben2ene and leukemia. Environ Res 11: 122-27, 1976. 13. Wurster-Hill DH. Cornwell GG 111. McIntyre OR: Chromosomal aberrations and neoplasm--A fam ily study. Cancer 33:72-81, 1974. 14. Berlin M, Gage J. Jcnnson E: Increased aromatics in motor fuels--A review of the environmental and health effects. Work-Environm.-Health 11: 1-20, 1974. 15. 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DiGuglielmo G, lannaccone A: Inhibition of mi tosis and regressive changes of erythroblasts In acute erythropathy caused by occupational ben zene poisoning. Acta Haematol (Basel) 19:14447, 1958. 22. Nissen Nl, Soeborg Ohlsen A: Review and report of a case in a benzene (benzol) worker. Acta Med Scand 145:56-71, 1953. 23. Galavotti B, Troisi FM: Erythroleukaemic mye losis in benzene poisoning. Br J Ind Med 7:79-81, 1950. 24. Aksoy M, Dincol K, Erdem S, D'ncol G: Acute leukemia due to chronic exposure to benzene. Am J Med 52:160-66. 1972. 25. DeGowin RL: Benzene exposure and aplastic anemia followed by leukemia 15 years later. JAMA 185:748-51, 1963. 26. Delore P, Borgomano: (Acute leukemia in the course of benzene intoxication.) J Med Lyon 9:227-33, 1928 (Fre). 27. Ishimaru T, Okada H. Tomiyasu T, Tsuchimoto T, Hoshino T. tchimam M: Occupational factors in epidemiology of leukemia in Hiroshima and Nagasaki. Am J Epidemiol 93:157-65, 1971. 28. Milby TH, Key MM. Gibson RL, Stokinger HE: Chemical Hazards, in Gafafer WM (ed): Occupa tional Diseases--A Guide to Their Recognition, PHS publication 1097. U3 Dept, of Health, Edu cation, and Welfare, Public Health Service, 1964, pp 87-89. 29. Communication of the Working Group "Establishment of MAK-Werte" of the Senate Commission for the Examination of Hazardous Industrial Materials. Considerations Bearing cn the Ques tion of Safe Concentrations of Benzene in the Work Environment (MAK-Wert). Prepared in co operation with Dr. Gertrud Buttner. Bonn-Bad Godesberg, Deutsche Forschungsgemeinschaft, 1974, 63 pp. 30. Lignac GOE: (Benzene leukemia in man and white mice.] Klin Woehenschr 12:109-10, 1932 (Ger). 31. Hess, W: (Respiration and fermentation in ex perimental benzene leukemia.) Z Pathol 47:52233, 1935 (Ger). 32. Hamaguchi. I, Yoshida, S: [Changes to the lym phatic glands, the spleen and the liver following long-term injection of very small quantities of benzene in animals.) Jpn J Med Sci, VIII, Int Med, Pediat & Psychiat 4:379-81, 1938 (Ger). 33. Kirschbauf A. Strong LC: Influence of carcin ogens on age Incidence of leukemia in high leu kemia F strain of mice. Cancer Res 2:841-45, 1942. 34. Amiel J-L: (Negative attempt at induction of leukemia in mice by benzene.) Rev Franc Etud Clin Biol 5.198-99. 1960 (Fre). 35. Aksoy M, Dincol K. Akgun T, Erdem S, Dincol G: Haematological effects of chronic benzene poison ing in 217 workers. Br J Ind Med 28:296-302, 1971. 36. Aksoy M. Dincol D. Erdem S, Akgun T, Dincol G: Details of blood changes in 32 patients with pancytopenia associated with long-term exposure to benzene. Br J Ind Med 29:56-64. 1972. 37. Akscy M, Erdem S. Dincol G: Two rare complica tions of chronic benzene poisoning--Myeloid metaplasia and paroxysmal nocturnal hemoglobinura--Report of two cases. Blut 30:255-60, 1975 38. Aksoy M. Erdem S, Erdogan G. Dincol G: Acute leukaemia m two generations following chronic evposure to benzene. Hum Hered 24:70-74, 1974, 39. Aksoy M, Erdem S, Dincol K, Hepyuksel T, Dincol G: Chronic exposure to benzene as a possible contributary etiologic factor in Hodgkin's dis ease. Blut 28:293-98. 1974. 40. Vigiiani EC. Saita G: Benzene and leukemia. N Engl J Med 271:872-76, 1964. 41. Stieglitz R, Stobbe H, Schuttmann W: [Leukosis induced by benzene.) Arch Geschwulstforsch 44.145-48, 1974 (Ger). 42. Erdogan G, Aksoy M: Cytogenetic studies in thir teen patients w>th pancytopenia and teukaemic associated with long-term exposure to benzene. New Istanbul Contrib Clin Sci 10:230-47, 1973. 43. Gallagher RE. Gallo RC: Type C RNA tumor virus isolated from culturea human acute myelogenous leukemia cells. Science 187:350-53, 1975. 44. Maugh TH II: Leukemia--A second human tumor virus. Science 187:335-36, 1975. 45. Todaro GJ, Huebner RJ: The viral oncogene hy pothesis--New evidence. Proc Nit Acad Sci 69:1009-15. 1972. 46. Gerarde HW. Toxicology and Biochemistry ef Aromatic hydrocarbons. New York. Elsevier Pub lishing Company, I960, pp 97-108. DO 06R474 CONFTDFNTTAL i crwn rawac * nu kti- t i?.** / YZ0012155