Benzene, Myelofibrosis and Myeloid Metaplasia
Case Reports of this Chemical Disease
Several case reports of myelofibrosis resulting from benzene exposure have been published in the medical literature.
The causal relationship between chronic benzene exposure and myelofibrosis was first reported by Gall in 1938. Gall, E. A., "Benzene Poisoning with Bizarre Extra-Medullary Hematopoiesis," Arch. Pathol. 25:315-326 (1938).
In 1939, Mallory described 2 benzene-exposed patients whose bone marrow was completed replaced with myelofibrosis. Mallory, T. B., et al., "Chronic Exposure to Benzene (Benzol): III. The Pathologic Results," J. Ind. Hyg. Toxicol. 21(8):355-377 (1939).
In 1941, Rawson reported benzene to be the cause of myelofibrosis in 3 of 6 workers diagnosed with the disease. Rawson, R. W., et al., "Industrial Solvents as Possible Etiologic Agents in Myeloid Metaplasia," Science 93:541 (1941).
In 1950, Wyatt reported 4 cases of benzene-induced myelofibrosis. Wyatt, J. P., et al., "Chronic Marrow Failure, Myelosclerosis, and Extramedullary Hematopoiesis," Blood 6:329-347 (1950).
In 1960, McLean reported a case of hemolytic anemia with myelofibrosis in a 27-year-old who was exposed for 12 months to benzene from gasoline lying on the ground while employed by an oil company. McLean, J. A., "Blood Dyscrasia After Contact with Petrol Containing Benzene," Med. J. Australia 47:845-849 (1960).
In 1965, Port reported a case of benzene-induced myelofibrosis in a 50-year-old Black woman who had worked as a hand presser for 30 years using cleaning fluids containing benzene. Port, M., et al., "Myeloid Metaplasia as a Result of Chronic Benzene Intoxication," N.Y. State J. Med. 65:2260-2262 (1965).
In 1967, Zini reported a case of benzene-induced disease developing into acute leukemia with myelofibrosis. Zini, C., et al., "[Pseud-Pelger Leukocyte Anomaly in a Case of Benzene Hemopathy with Acute Terminal Leukemia]," Haematologica 52(3):258-266 (1967).
In 1973, Biscaldi reported a transient case following an 8-year exposure to benzene. Biscaldi, G. P. et al., "Acute Panyelopathies Due to Benzene: Description of a Case with Favourable Outcome," Med. Lav. 64:363 (1973) [English abstract Ind. Hyg. Dig. 1109 (1974)].
In 1975, Aksoy reported a fatal case 8 years after the occurrence of aplastic anemia due to chronic benzene exposure. Aksoy, M., et al., " 2 Rare Complications of Chronic Benzene Poisoning: Myeloid Metaplasia and Paroxysmal Nocturnal Hemoglobinuria: Report of 2 Cases," Blut 30:255-260 (1975). In 1977, Aksoy reported on another case - a 21-year-old technician who was exposed to benzene for 4 years before developing the disease. Aksoy, M., et al., "Followup Study on the Mortality and the Development of Leukemia in 44 Pancytopenic Patients with Chronic Exposure to Benzene," Blood 52(2):285-291 (1978). Aksoy later reported a third case in a benzene-exposed painter. Aksoy, M., Benzene Carcinogenicity at p. 102 (CRC Press 1988).
In 1978, Iwata reported a case of benzene-induced aplastic anemia which developed into acute myelogenous leukemia with meylofibrosis. Iwata, N., et al., "[A Case with Aplastic Anemia Presumably Related to Benzene Exposure Terminating in Acute Myelogenous Leukemia Associated with Myelofibrosis]," Rinsho Ketsueki 19(9):1234-1240 (1978).
In 1987, Hu reported a case of benzene-induced myelofibrosis in a 54-year-old woman who had, for 23 years, made handbags, using benzene to remove excess glue from the handbags. Hu, H., Benzene-Associated Myelofibrosis," Ann. Intern. Med. 106(1):171-172 (1987).
In the late 1980s, Bosch reported a case of myelofibrosis in a worker who, for more than 40 years, had used toluene to dissolve industrial glues. Bosch, X., "Myelofibrosis and Focal Segmental Glomerulosclerosis Associated with Toluene Poisoning," Human Toxicol. 7:357-361 (1988); Bosch, X., "Toluene-associated Myelofibrosis," Blut 58:219-220 (1989).
In 1989, Antonucci reported another case of benzene-induced myelofibrosis, in a worker who had 20 years earlier developed severe aplastic anemia after using a paint remover containing 50% benzene to strip paint from furniture. Antonucci, R., et al., " Myelofibrosis and Aplastic Anemia: First Report of the Two Disorders Occurring Sequentially in the Same Person," Am. J. Med. 86:352-355 (1989).
In 1990, Uppenkamp reported a case of benzene-induced myelofibrosis from exposure to paint. Uppenkamp, M., et al., "[Benzene-Associated Myelofibrosis at an Early Stage]." Internist 31(12):769-772 (1990).
In 1995, Tondel reported a case of myelofibrosis in a 46-year-old man who had worked as a gas station attendant for 17 years and was exposed to benzene from fueling cars with gasoline and diesel and from inspecting the level of gasoline in arriving tanker trucks. Tondel, M., et al., "Myelofibrosis and Benzene Exposure," Occup. Med. 45(1): 51-52 (1995).
In 2005, Bernardini reported a case of benzene-induced myelofibrosis in an automobile mechanic who had used gasoline to degrease automobile parts for 42 years. Bernardini, P., et al., "Myeloproliferative Disorders Due to the Use of Gasoline as a Solvent: Report of Three Cases," Med. Lav. 96(2):119-125 (2005).
Epidemiologic studies of myelofibrosis are few because the rarity of the disease does not readily lend itself to epidemiologic analysis. However, the disease has been evaluated in a few case-control studies and a few cohort studies.
In 1971, Girard reported that of 13 patients with myelofibrosis, 2 (15.3%) had a history of exposure to benzene or toluene. Girard, R., et al., "Malignant Haemopathies and Benzene Poisoning," Med. Lav. 62(2-3):71-76 (1971).
In 1983, Rushton reported a nexcess of myelofibrosis deaths among workers at oil distribution facilities in Great Britain. Five deaths were attributed to myelofibrosis, when only 1.81 deaths were expected, yielding an odds ratio of 2.76 which was statistically significant (p < 0.04). Rushton, L., et al., "Epidemiological Survey of Oil Distribution Centres in Britain," Brit. J. Ind. Med. 40:330-339 (1983).
In 1986, Zoloth reported 3 deaths from myelofibrosis among 1,427 death certificates of pressmen exposed to benzene from solvents. A proportionate mortality ratio for myelofibrosis was not reported, probably due to an absence of data regarding incidence of the disease in the general population. However, given the rarity of the disease, 3 cases in a cohort of this size is a statistically significant excess of the disease. Zoloth, S. R., et al., "Patterns of Mortality Among Commercial Pressmen," J. Nat'l Cancer Inst. 76(6):1047-1051 (1986).
Also in 1986, Kaplan reported 3 deaths from myelofibrosis in a mortality study of petroleum refinery workers - more than twice the expected number of deaths from the disease. Kaplan, S. D., "Update of a Mortality Study of Workers in Petroleum Refineries," J. Occup. Med. 28(7):415-516 (1986).
Also in 1986, Ott reported one death from myelofibrosis in his update of the Dow Chemical Company cohort. Bond, G. G., et al., "An Update of Mortality Among Chemical Workers Exposed to Benzene," Brit. J. Ind. Med. 43:684-691 (1986).
In 1991, Marsh reported an excess of myelofibrosis at Shell's Deer Park petrochemical complex. Marsh, G. M., et al., "Mortality Patterns Among Petroleum Refinery and Chemical Plant Workers," Am. J. Ind. Med. 19:29-42 (1991).
In 1995, Honda reported a statistically significant excess of myelofibrosis and myelodysplasia among refinery workers at Shell's Wood River refinery in the 1980s (4 cases observed, < 1 expected). Honda, Y., et al., "An Updated Study of Mortality Among Workers at a Petroleum Manufacturing Plant," J. Occup. Environ. Med. 37(2):194-200 (1995).
Numerous case reports of benzene-induced myelofibrosis have been documented in the medical literature, and the causal association between exposure to benzene and myelofibrosis is supported by the available epidemiologic literature. There is sufficient evidence to conclude that benzene causes myelofibrosis.
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