Document Rp9g00bGBEEJ6GoYRnVw8Gy2V

Occupational Health LEUKEML4 IN BENZENE WORKERS ,:;I;*-*::;;;ROEERTA. RINSKY RONALD 3. YOUNG Indusrry-wide Studies Branch, Division of Survrillrrnce. Hazard Ecaluarions and FieldStudies, NariondInstirure for OccrippJtionalSafety and Health, Centerfor Discare Control, Cincinnati, Ohio 45202, USA. Summary Workers occupationally exposed to benzene in 1940-49 were followed for vital status u p to 1975. In comparison with two control populations, a significant (~(0-002)cxcc50 of leukzmia was en_dof the study period. The environm<nt of the workers i n the study popula- tion was not contaminated with solvents other than benzene and existinp records indicate that the benzene `levelsthemselves were generally below the iimits recorn; mended at tne time ot thrrr measurement. INTRODUCTlON OXEof the earliest reports of benzenerelated blood disorders consistent with what is now known to result from benzene poisoning was published in Paris in 1897.' In 1928, a clearly established case of leukgmia was associated with benzene exposure in 1taly.l Since then, many cases of h k a m i a associated with exposure to benzene have been reported from various parts of the ~ o r l d . ~A - s~ignificant excess of chromosomal aberrations has also been observed in benzenc-cxposed workers.to Ishimaru et aL6demonstrated a significant association between leukamia and occupations with probable e x p sure to benzene, and Aksoy e t al.' reported a significantly greater incidence of lcukacrnin in shoe workers exposed to benzene than in the general population. In 1976 \'igliani* reported that IS0 cases of leukzemia attrilnited to benzene had been i d e n t i k l in Italy. McMichaeI et al." demonstrated a n excess of leukamia among rubber workers previously exposed to solvents, including benzene. However, in that study the lcukemr*genic effect could not be attributed directly to benzene because of concomitw~texposure to other solvents used in thc msnufasrure of rubber products. 1More the 1914-18 war, benzene was used mainly as a solvent in the rubber industry, but during the war the deriiand for toluene in the manufacture of explosives greatly $timulared benzene production. Currently, S7% of bsnlene is used as a raw material in t h r synthesis of cornp:,undb such as styrene, phenol, and cyclohtxane. Approxirna1cly 10.2 billion Ih (4.6 billion kg) were pro- duced in the U.S. in 1973, 3.5 billion Ih (1.6 billioii kg) in Japan in 1972, and 1.2 billion lb (0.5 billion kg) in the U.K. in 1972.'' In the SO years since the firs1 reported case of benzeneassocialed leukamia, benzene has been neither widely acknowledged nor iiniformly controlled as a carcinogen in the U.S." The failure to control benzene as a carcinogen has resulted primarily from the reluctance of industry and Government LO accept the accumulated case-reports and epidemiological observations as scientific evidence of the leukaernogenic properties of benzene. Today, in 1he US. alone, an estimated two million workers are at risk of exposure to benzene.'* For these reasons we have studied mortality patterns in workcrs occupationally cxposcd to benzene in the production of a natural rubber cast film (rubber A -hydrochloride, marketed under the trade `Pliofilm') at two localities in Ohia INDUSTRIAL-HYGIENE ASSESSMLVC Production Methods name P il In tbe production of `Pliofilm', narual rubber \vas matti- catcd in an internal mixcr, passed through P mill, and.conveyed IO mixing-tanks, where benzene was addcd and the mix- ture was agitated. The resulting solution was pumpcd to a blending-tank, then transferred into il reactor vessel, when ii was treated with hydrochloric add to form rubkr lipdnrhloride. At this stage, more benzene was added IO adjust the proportion of solids in the solution. T h e rubber hydrochloride was transferred to a neutralising-tank, whexe pliofilm straps, soda ash, steam, plasticisers, and more bmzene were added. After filtration, the rubber hydrochloride solution was pumped to a casting-unit, then it was spread on a coniinuous conveyor, where the benzene was evaporated, and the finished film was taken up on a roll. T h e gss containing btnzene was exhausted from the casting-unit, passed through a ,wet scrubber, and channelled into an activatedeharcoal absorber unit, where benzene was recovered and recycled. The rolls of pliofilm were transferred to another room, where they were inspected, trimmed, CUI to customer specification, and packed (primarily for food wrapping). In the production o f pliofilm, the only material known to bc associated wiih blood disorders was benzene. Other malerials uscd included hydrochloric add, soda ash, and small amounts of antioxidants and plasticiscrs The manufacturing process w m essentially identical at borh Ohio localities. Environmental Monitoring In 1942, Wilson, as a former inernbciof corporate msnago ment, recommended a policy for the rubber industry, which would include pliofilm operations, of periodic air monitoring and a complete blood-count for all nnv ernployca." It was his view that "a closcd system of ventilation where the workman coma in contact with no f u m a is ideal. Any other iype of ventilation is not entirely safe." Shortly thereafirr, extensive exhaust ventilation equipment w3s installecl in the pliofilm department in occ locality. The Industrial Commission of Ohio, after surveying that depariment in 1946, reported that, "Tests were made with benzol detectors and the results indicate that concentrations have been reduced IO a safe lcvcl and in most instances range from zero to 10 or I S parts ptr million"." A further invrsligation of bcnzcnr exposure in that department in 1956 cancliided hat exhaust ventilation COW trols were of cxcelleni design." In the cnrly 1960s benzene point-source concentrarions were measured by compmry personnel using detscior tubcs. A total of 112 survrys werc COIIducted in the period 1963-74. These and cnrlier survqs liavc iridtcaid that ernployecs' benzcnc expowre WRS ficncrdly below the rccornmctlcicd limit in effect ai the time nf each sur- v ~ y ~ ' . ' ' . '"~'(table I). , 4 >. T A D L t I--CHRONOLOGY Ok RECOMMENDED BLhZEhE K csI i I15 C O K C t N T R d T I U \ S IP; H O R I P L A C E S I V ti S A . T'hrrc tvcrc 140 observed deaths from all causes Ccmccriiratinn p p ni among bcniciicyxposed workers comparcd with 187.6 cxprctcd dz,trhs (table 11). This deficit reflects in part the incomplctc L;~llow-upof the study popularion. There was f SO Bh ~ W . A a significant cxcess of deaths from malignancy of the 1948 35 Sh TW.A 2 5 8 h 1.w.A. 14 25 Cziling 1971 I 10 8 h T W . A . 10 8 h. W~. A . I II M.A.c.=Maximum allouablc conccntriioon. r.w.A.=Time-aeighred avcrage. Iymphaic :ind haniopoietic systems (I.C.D. 200-205) cornpared t o ttxlr expected on the basis ofdeath-rates of U.S. 'A'hitc males. This is due almost enrirely IO an excess of Icukxmia deaths (I.C.D. 204). To date, 7 kuksmia Jc:iths have been observed, compared with an cxpectcd 1 . 3 s (~(0.002) based on rates for U.S. White males a n d nil expc.c~cd1.48 (~<0-002b)ased on rates for fihrou\-i:lass workers. Even more striking is the Historical environrncntal data for the second locality in obrervatioil that all 7 leukemia deaths were from either Ohio is Ias well defined. Houever, our own observations, dis- the rnyrloptmus or monocytic type. Data for cell type, cussions with company personnel, and the meagre environmenla1 data that have been retained suggest that employees' benzene exposure at this location was generally well within the recommended limits. age a t Jcarh, and i n r e n d since initial exposure t o benzcne arc shown in table 111. T h e period between initial exposurc and death ranged from 2 t6 21 years. These obsewations, indicating a specifictype of lenkamia, are Mcrhods RETROSPECTIVE COHORT STUDY consistent tviih the data of Vigliani: which show a predominance of acute myelogcnotis lciikaeniia among workers exposed to benzene in the rotogravure and shoe- &)%he men who had had direct exposure to ben- manufacturing industries in Italy. Since data for specific zene at any time beween Jan. 1, 1940, and Dec. 31, 1919, were studied. The deiartments and jobs involving direct exposure to benzene were determined by a survey by K.I.9.S.H. personnel, which included a review of the pliofilm process, engineering controls, and air-sampling ' data. Company personnel also assisted in these determinations. Job classifications involving benzene expo- sure were determined without knowledge of the workers' vitalstatus. '. Follow-up of all study-cohort members was attempted Eenzenezxpoxd for the time period from first employment to -0, 1975. To date, vital status has been determined for approximately 75% of the 748 cohort members. The remaining 25% were assumed to be alive to avoid overes- Causes or Jmth (1.C.1). crwltr)' workers Deaths observed Dcaihs cxpcaed Comparison group S.M.R. timating the true risk of lymphatic and hremopoietic malignancies associated with benzene exposure. C a u s a of death were determined from death certificates and were coded according to the International Classification All causes '200-20s) (204) 200-205) I40 9 7 9 187.5809 3-4497 1-3631 5.1020 (u.s.w.K..) (u.s.w.M.) (U.S.W.M.) (F.G.) 075 260t S06$ of Diseases in effect at the time of death; these codes ('0.1) 7 1-4758 (T.G.) 474$ were then converted to I.C.D. 7th revision numbers. A modified lifetable technique was used to generate per- son-years at risk of dying according to 5-year age-group and 5-year calendar periods. Person-years of observation and causes of death were determined for the period Jan. 1, 1950, to June 30, 1975. Person-years of observation and deaths occurring TABLE Ill-CASES OF I.LUKEJAIA IDENTIFIED UY APRIL, 1977, before Jan. 1, 1950, were excluded from analysis sincc AMONG WORKERS EXPOSED TO BENZENE RETWEEN 1940 AND I vital statistics on lymphatic and hamopoietic malignan- I949 DURlNG PLIOFILM MANUFACTURE .f cies were not published before that date. Two populations were chosen as control groups for generating the numbers of expected deaths in the study population. T h e first group consisted of the U.S. White male general population standardised for age arid time period o v e r which the study cohort lived. The second e group consisted of 1447 White men who had been employed in Ohio at a fibrous-glass construction-pro- d u m factory between Jan. 1, 1940, and Dec. 31, 1949, C and who had achieved 5 or more years of employment Y by June 1, 1972 (which was the cut-off date for vitnl- status ascertainment in the fibrous-glass control popula- tion)." 78 TllE L.ANCET, JULY 9,1977 types of Icukrrmia mortality in the U.S. are not readily available for the study period, incidences for myeloid, monocytic, and total leukmnia from the Connecticut Before Our Time Tumor Registryzz for the period 1960-62 were applied to the age-itistribution of the benzene-exposed cohort to generate the specific proportion of total-leukzmia cases OPIUM AND THE HISTORICAL P E R S P E C m which would be of the myelomonocytic types. Of the total expected number of incidence cases of leukxmia, 50.37r; were calculated to be of the myelogenous and monocytic types. This proportion was applied to the \'lRGlSlA nEPJ1,DGE Addiction Rcsearclr rJnit, lnsnkrre of Psychiatry, London SES total number of expected leukzmia deaths in the study cohort which had been previously generated on the basis ofrates for the U.S. White male population. The results indicated an expected 0.6967 (0.5037 x 1.3831 = 04967)deaths from myelogenous and monocytic leukz- The literature produced over the last ten years analysing and describing the "drug scenc" in the United Kingdom has almost totally neglected the historical examin* tion of English drug, and especially opiate, use. The mia, compared with 7 observed, the standardised morta- lity-ratio being 1004. Thus, pliofilrn workers exposed 10 benzene have an estimated 10-fold risk of dying from ,myelogenous and monocytic leukzmia. As a result of past failure to control benzene as a car- c i n w n s ot Deogle, without knowledge of the haemopoirtis d a n g e .w. continually being exposed to -benzene at ;vork&addusn, unknown numbers 01 con- s'umers. includin"e children. are exDosed to benzene at home. pai - . sources ~ r 9h% our findings, wl ich demonstrate ove t 7whelmingly an increased risk o! leukremia in workers familiar examples are quoted and re-quoted; reference to the mid-19thcentuq opiuni wars abound. But how did ordinary people use opium in the 1820s, when De Quincey was writing his Confessions? How great a danger did the unrestricted sale ofopium pose? How did the medical profession, the chemists, and the public a i large react? Such questions have remained largely un- answered; and yct responses to them arc needed if a pro- perly informed perspective is IObe given to the currcnt worries, and a more rational appraisal made of c o n t m porary attitudes and policies. UNRESTRICTED OPIATE USE exposed to benzene, will stimulate efforts to control I Narcotics have been undcr strict legal control almost Loccupational and consumer exposure to benzene, an agent known for almost a century to be a marrow poison.' as long as anyone can remember-there can be few doctors now in practice whose professional experience goes back to the years before the first Dangerous Drugs Act became law in 1920. I t is therefore instructive to recall We thank Mm He~s! Egan and M r David Rrown and the entire s u p port z u f T of the biomerry section, National Institute for Occupa~ion;ll that, up to 1868, opium and cannabis (in fact then Sakty and Ilealth, for their dedication and assistance during the rarely used) were available over the counter without any study. form of restriction, Jmponed opium, mostly Turkish in R C J U ~f~urI SrcprinrsshoulJbe addressed to 1'. F. 1. origin, could be bought almost anpvhefi-not just from chemists, druggists, or pharmacists, but in village shops, REFERENCES from grocers, general stores, and corner shops in the 1. 1.eS.w. C. ftirlf, MI%. S w n d . i/+Pa.ris 1897, 3, 1211. I , . . Ht,rprnano.C.J. .Vdd. L v m 1928.9.227. A , Cavi-gn~run.A,. Hcrnarii. J. Nour. R c r u z f r Hcmur. 1967. 4, back streets of the growing industrial cities. The I - l ~ l t coroner, for inslance, noted in 1854 after an inquest on an infant poisoned with laudanum sold in mistake for V r g I i ~ n t .E . C . A n n . N . Y . R i a J , S c i .1976,271,143. ?. l,u&ig.V, II..Utrlhzmann,A.Schp.ri:. wed. U i c h r . 1962.92.378. @I\htrnJru. .I. Okada. 11.. Torniyaru. T., Truchimoto, T.,Horhina. T.,Ichi- 0 .maru.~l.r(~..f.EFidsm.1971.93.157. Akuir. ,31,%ErJrm.S.. IhnCol. G.R / w d . 1974.44.837. 8 . $ 1 J l h L , 'I.14.. (;all. E.A., tin&lc).. W. J . J .;*J. H.b.8. T ~ I ~ u19/39.. 21, syrup of rhubarb, that the liquid opiate "was kepi with several orher bottles of similar shape and appearance on a shelf in the shop window of a Grocer in a distria thickly inhabited by factory operatives, and was given to a messenger between six and seven years old".' Acceptance of the drug wtnt so far as io cncourage enterprising farmers, doctors, and market gardeners to experiment with thc cultivation of a British variety. Mcssrs Cowley and Staines, for instance, who cultivated several acres at \Vinslow in' 1823, managed to produce 186 Ibs of opium from 12 acres of land. Their profit, in- cluding the yield from a crop of lurnips pmdenily plantcd in addition, was over l 9 6 an acre; others reported similar successes, slrhough "the prccarioiisness of our clinlate" was universally recognised as a draw- b;lck.'*' Hritish opium was never generally used; hut opiates- chicfly laudanurn, the camphorated tincture known 3 s parqpric clisir, and raw opium, sold in pills and pciiny sricks-were widely used both on medical prcsrripiion ant1 ;IS self-nieJication by those who coiild not atford Incdicul treiitnisni. I n one area of thc country, the low-lying, nixshy, agileridden Fens, it was accspied 11131 opiait. uw 011 n regular and sustained basis was