Document BvZyn2M0xZKXdE249bOG31eE

nor ciil dat -ipt bS&. WJ, ifor- dam nent xidc. ntra1 for rcuii vol. Val. :om. imal diiy mal ullr. pr- li 1. day '-rom Med ISCI. ork: s in 74. n S. bas U"U ten( /-up ntra PPI): ILO ws. :ria tion 'spc COT vul- ~ I jj f British Journul of' Industrid Medicirie 1987;44:785.-787 Exposure to benzene in Turkey between 1983 and 1985: a haematological study on 231 workers PLAINTIFF'S EXHIBIT M AKSOY,' S t)ZERk$,' H SABUNCU,3 Y fNANICI,' R YANARDAG' From the Department of Biology,' Gebze, Kocaeli, Research Institutefor Basic Sciences, Scientific and Technical Research Council of Turkey; and Engineering Faculty' und Department of Public Health,3 Istanbul Universily,Capa-Istanbul, Turkey 20 00 8- E23 a3 $ 3 2.s TRACT A study was performed to determine the content of benzene in the air and solvents and ,hinners used by 231 workers in 40 small or large workplaces in Istanbul and Izmit. The benzene E =- '=cmi-*" E U, d u e in the air of a tyre cord manufacturing factory where two cases of acute leukaemia were worded in a six year period was I10 ppm. In nine of 47 thinners (19.1%) the benzene content ,anged between 0% and 6.4% whereas it was between 0.7% and 7.64% in 26 of 34 solvents used. \ haematological study on 231 workers showed that there were mild abnormalities in 14 workers ncluding leucopaenia in nine (3.9'/0), thrombocytopaenia in four (2.16%), and pancytopaenia in )ne (0.54%). This study shows that despite the considerable decrease in the content of benzene in he solvents and thinners available in Istanbul and Izmit the percentages of benzene in most of the .E 5 .. 4 .=U cJ=n & )r 2u naterials are still above permissible limits. The effects of chronic benzene toxicity are well known md include leucopaenia, thrombocytopaenia, iplastic anaemia, chromosomal aberrations and leukaemia.'-3 In 1971 one of the present authors ind his associates published the results of a iaematological study on 2 17 workers chronically :xposed to benzene in Istanbul.' In that study iaematological abnormalities attributable to chronic nnzene toxicity were detected in 51 of 217 workers 23.5%). Additionally, in this period (1962-71) iumerous cases of aplastic anaemia and malignant ymphoma due to the use of benzene have been ,eported,mostly from the same workplaces where the 'rbove mentioned studies were performed.'- Since 1969there has been a gradual prohibition and discontinuation of the use of benzene in Istanbul. Due to this fact, a striking decrease in the number of the vic- 'tims of chronic benzene toxicity has bccn recorded since 1975.' We thus decided to perform a haematological study on 231 workers in Istanbul and Izmit, a town close to Istanbul, where solvents, thinners, and similar materials were used. Accepted IO November 1986 Material and methods Between 1983 and 1985,231 workers employed in 40 workplaces in Istanbul and Izmit, consisting of small and large shoe manufacturing plants, leather workshops, repair plants in airport and dockyards, automotive plants, farm vehicle manufacture and repair plants, and tyre cord and tyre fabric manufaluring plants were studied haematologically. All except four were men and their ages ranged from 14 to 57 (mean 32-7). The duration of exposure was between one month and 40 years (mean 8.8 years). In eight workers the duration of exposure was less than one ycar. Blood samples were collected in heparinised bottles and two peripheral blood smears were prepared from each person. Blood counts were determined with either a Coulter counter ZF or a Technicon 102. Platelet counts were estimated with a Coulter thrombocylometcr or by the Brcchcr Cronkite method6; blood films were stained by the May Grunwald Giemsa method. Benzene in solvents, thinners, air, dyes, and lacquers were determined by gas chromatography.' In this method three columns were used for analysis. The first column, loft x 1/8" stainless steel, was packed with 5% Carbowax, 4000 TPA 786 Table I Aksoy, Ozeriq, Sabuncu, hanici, Yanarhf Biwzctrr c.onc.etitrutioti in 108 tnurcriuh collected in 40 workshops in lstanhuland lzmii between 1983 and 1985 ~ Mean benzene (%) ~ ~~ Percentageof specimens containinn more than I % of benzene Air Thinner Solvent Dye Lacquer 13 47 34 9 5 0- I IO ppm 0-6.6 0.7-7.64 0- I .46 &very little 0.73 0-73 2.88 0.32 7.7 19.1 76.4 11.1 Table 2 H u ~ m u r o l o ~ i cdaalta ohtuiticd it1 231 workers eniployecl in 40 workshops in lsianbul and lzmit N o of workers studied Upper value Lowest value Mean value Standard deviation No (%) of workers with values lower than normal 23 I 16.4 10.1 13.5 k0.7 20 (8.7) 23 I 57 36 44.0 k2.I 32 (13.86) ~ 226 5.8 3.6 4.8 f0.2 ~~ 24 ( I 0.6) 23 I 14.8 3. I 6.9 It: 1.3 IO (3.9) I86 410 I I7 224 & 40-0 5 (2.16) Table 3 Differential counts in 186 workers using materials containing benzene in Istanbul and lzmit Polyniorpbonuclear nrutroplrils (Yo) Range Mean value SD & No (%) of workers with abnormal values 40-74 62.8 4.3 I (0-5) molBandform 0-5 1.8 0-7 0 Lymphocytes (%I I658 35.1 2.6 I(0.5) Monocytes 0-14 4 1-6 8 (4.3) Eosinopliils (%) 0-12 2-7 0.8 5 (2-7) Basophb 1%) 0-4 0.2 0.2 3 (1.6) 80/lOO mesh Firebrick. The second column, 20ft x 1/8"stainless steel, was packed 20% SE 30 Chromo- sorp P 60:80 mesh AW. The third column, 20ft x 1/8" stainless steel, was packed with 10% SP-1000, 80/lOO mesh Supelcoport. Case reports Case I-A 23 year old worker with 28 months exposure to benzene containing solvents and thinners in a modern tyre cord manufacturing plant developed acute myeloblastic leukaemia. He had a severe pancytopaenia and a hypercellular bone marrow with 71% myeloblasts associated with Auer's rod. The working conditions were good and the workplace was large and properly ventilated. The concentration of benzene measured by gas chromatography in one part of the plant was 1 IO ppm and in one of the solvents used in an auxiliary repair shop the benzene content was 5.9%. Case 2-A 30 year old worker with four years exposure to benzene in thc factory mentioned above developed acute lymphoblastic leukaemia. He had severe pancytopaenia and a hypocellular bone marrow with 36% lymphoblasts. Case 3-A 42 year old worker with five years exposure to benzene containing solvents and thinners developed acute myelomonocytic leukaemia. He had severe pancytopaenia with a mildly hypocellular bonc marrow associated with 25% myeloblasts and 51% atypical monocytes. In the solvent and thinner used in one section of the plant the benzene contents wcrc 7.4% and 4% respectively. Case 4-A 48 year old worker with I5 years exposure to benzene containing solvents and thinners in a large automotive plant developed Hodgkin's disease. He had cervical lymphadenopathy and mild hepatosplenomegaly. The results of a pathological study showed Hodgkin's disease with lymphocytic predominance. The solvent and thinner containcd 3.1 % and 6 4 % of benzene. Case 5-An 18 year old worker in a large shoc manufacturing plant developed axillary and inguinal lymphadenopathy after two years exposure to bcnzene. Pathological examination of one of the lymph nodes showed a poorly differentiated lymphoma. In Ex\ me i.9' lesl ihc vor 13 a 'P* ,hin I Yo [76. bet\ nint lhai tior or t 7 car1 hac B/d WOI 12 bct SD 3.1 SD COl for I os thil (2.. wo dif Chi eo: (1. co As 19 pl; of (m 0.' thm th' co I R E.fposure to benzene in Turkey between I983 und 198s: u huemu~ologicusl rudy orl 231 workers 787 one of the solvents used the benzene content was 6.9%. Results The benzene content of 108 materials used in 40 workshops are summarised in table I. In only one of 13 air samples was the benzene content more than 1 ppm; in this sample it was 110 ppm. In nine of 47 thinners (19.1%) the benzene value was more than I%, ranging to 6.6%. Similarly, 26 of 34 solvents (76.4%)contained more than 1 Yoof benzene ranging between 1.1% and 7.64%. By contrast, in only one of nine samples of dyes was the benzene content more ihan 1YO.Five lacquers contained no benzene. Addi- tionally, in toluene and heptane samples the amount of benzene was 2.8 and 4.2% respectively. Table 2 gives the results of a haematological study carried out on 231 apparently healthy workers. The haemoglobin content ranged between 10.1 and 16.4 ddl (mean: 13-51 g/dl, SDkO.74) and only in 20 workers (8.7%) was the haemoglobin level less than 12 g/dl. The PCV ranged between 0.36 and 0.57 1/1 (nican: 0.44, .SD+_O-IQ);the red cell counts were bctween 3-6 and 5.8 x 10'2/1 (mean: 4.81 x 10'*/1, SDk2.10) and the white cell counts ranged bctwccn 3.1 x 109/1 and 14.8 x 109/1(mean: 6.9 x IOy/l, SD+ 1.26). In nine workers (3.9%) the leucocyte counts were less than 4 x 109/l. Platelet counts performed in 186 workers were between 117 and 410 x IOy/I (mean: 224 x 109/1, SD+40-023); counts less than 150 x 109/1 were found in four individuals [2.2%). Pancytopaenia was observed in only one worker (0.54%). On the other hand, the results of the differential counts in 186 workers showed few changes with monocytosis in eight (4.3%), cosinophilia in five (l.6%), and basophilia in three (1.6%)(table3). Comment As may be seen in table 1, 76.4% of the solvents and 19.1% of the thinners used in 40 small or large work- places in Istanbul and Izmit contained more than 1YO 3f benzene; the range was between 0.7% and 7.64% [mean: 2.8%) in Istanbul and 0% and 6.6% (mean: 3.73%) in Izmit. If we compare these results with [hose of the materials used between 1970 and 1972 here is a significant but not sufficient decrease in the ;ontent of benzene in the materials used in thc work- shops in Istanbul and Izmit. At that time, the benzene content in the solvents used ranged between 0% and 88% (mc;in: 23. IS%) and in the thinners between 0% and 70.6/0 (mean: 30.7%). ( I Topuzoglu, unpublished data). Parallel to the Fall in thc bcnzcnc content in thc solvents and thinners used bclwcen 19x3 itnd 1985, a significant decrease in the haematological abnarmalitics attributable to this chcniical was observed in 231 workers employed in thc workplaces described above. One the other hand, the study performed among 217 workers heavily exposed to benzene in Istanbul showed that 51 (23.4%) had haematological abnormalities including leucopaenia, thrombocytopaenia, pancytopaenia and the pseudoPelger Huet anomaly.2 By contrast, other haematological alterations such as leucopaenia, thrombocytopaenia, and pancytopaenia were relatively uncommon. The differences in the proportion of haernatological abnormalities in the two studies is obviously due to the decrease in benzene content in the material used. Despite this, continuance of haematological abnormalities in workers in Istanbul and Izmit and the occurrence of five cases of acute leukaemia and malignant lymphoma in the same workshops clearly show that the deleterious effects of benzene. even in low percentages, continue in Istanbul and Izmit. Interestingly, four of these cases mentioned above had only a short duration of exposure to benzene, between two and four years. This study was supported by a grant from the Scientific and Technical Research Council of Turkey. References 1 Aksoy M. Benzene: leukaemia and malignant lymphoma. Topiccil Review iii Huenturology 1982;2:105-39. 2 Aksoy M, Dinqol K, Erdem $. Dinqol G. Haematological eliects of chronic benzene poisoning in 217 workers. Br J In11 M d 197 1;28:29&302. 3 Aksoy M, Dinqol K, Erdem $, Akgin T. Dinqol G. Details or blood changes in 32 patients with pancytopaenia associated with long term exposure to benzene. Br J lncl Mrcl 1972;29:56-65. 4 Aksoy M. Dilfereni types of malignancies due l o occupaticinal exposure to benzene: a review of recent ohservations in Turkey. Environ Res I980;23:18 1-90. 5 Aksoy M. Malignuncies due to occupational exposure to benzene. Am J lntl M r t f 1985:7:395-402. 6 Brecher C. Cronkite EP. Morphology and enumeration of human platelets. J Appl Physiol 1950;3:365-77. 7 White LD. Tnylor A. Mauer PA, Kuprl R E . A convenient optimized method Ibr the analysis of selected solvent vapors in the industrial atmosphere. Aut hrcl flyg A.WW J 1971;31:225.