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AMERICAN JOURNAL OF INDUSTRIAL MEDICINE 29~225-226( 1 996) EDITORIAL Benzene and Blood: One Hundred Years of Evidence Philip J. Landrigan, MD. MSC KEY WORDS: beniene, leukemia, lymphoma, aplastic anemia I n I977 we shall mark the one-hundredth anniversary of the publication of the first case report describing hematologic toxicity in a worker exposed to benzene (LeNoir and Claude. 1897). In 1998. we shall observe the seventieth anniversary of the first report clearly associating benzene with leukemia (Delore and Borgoinano, 1928). I n the century that has passed since the seminal observation that benzene is toxic to blood. a steadily accumulating body of data has shown to an ever-higher degree of certainty that benzene can cause a broad range of hematologic dysfunction, including all types of leukemia. lymphomas. rnyeloid metaplasia. and aplastic anemia (Young, 1989). These etiologic associations are substantiated by case reports. epidemiologic investigations. and laboratory studies. Benzene has been declared a proven human carcinogen by the International Agency for Research on Cancer, by the U.S. Environmental Protection Agency. by the United States Occupational Safety and Health Adniinistration. by the Nalional Institute for Occupational Safety and Health, and by occupational health and safety agencies around the world. The three papers in this issue of the Journal reconfirm benzene's ability to cause a wide range of hematologic toxicity. including malignancy. They clearly show that benzene can cause dysfunction of synthesis in all blood-forming elements. The effect can occur quite early in cell development. in some instances at the stem cell level. and is seen Mount Sinai School of Medicine, New York, NY Address reprint requests to Philip J Landrigan, M D , M Sc , Department of Community Medicine, Mount Sinai School of Medicine, One Gustave L Levy Place Box 1057, New York NY 10029-6574 Accepted for publication November 20, 1995 even at very low levels of exposure. In the paper by Yin et al.. ( 1 9 9 6 ~a statistically significant excess of deaths was noted for leukemia. malignant lymphoma. and non-neoplastic diseases of the blood. Risk was elevated for all lyniphohematopoietic malignancies, malignant lymphoma. and leukemia. Among the leukemia subtypes, only in the case of acute myelogenous leukemia did the excess achieve statistical significance at the 5%. level. but nonsignificant excesses were noted for chronic niyelogenous leukemia and for lymphocytic leukemia. Significant excesses were noted also for aplastic anemia and for myeloid metaplasia. The Rothman et al (1996) paper provides strong evidence for a dose-response relationship between benzene exposure and hematotoxicity. and identifies decline in the absolute lymphocyte count as particularly sensitive to benzene exposure. thus confirming an important finding by Goldwater in 1941. I n spite of industry's frequent claim that only acute inyelogenous leukemia should be considered caused by benzene exposure. this effect on lymphocytes at low levels of exposure establishes further biologic plausibility for the observed etiologic association between benzene and lymphocyte-derived tumors. The Rothman et al., results are corroborated by the positive findings of Ward et al., (1996). Ward and colleagues examined the effect of benzene on blood counts, but had data available on only total white and total red blood cell counts for the U.S. rubber worker's cohort. The strong negative dose-response relationships that are reported in this group between benzene and all white cells may actually underestimate the association between henzene exposure and depressed lymphocyte counts. The tragedy of henzene is that it has taken so long for science to be translated into protective action. Many thousands of workers and other persons in nations around the world have suffered unnecessarily and died prematurely 0 1996 Wiley Liss, Inc 226 Landrigan while regulatory agencies, industry, and the courts debated the carcinogenicity of benzene and argued about the need for protective regulation (Nicholson and Landrigan, 1989). In the current era of global proliferation of toxic chemical and hazardous technologies, all who are involved in the production and use of benzene have a heavy responsibility and a duty to protect their workers and the general public against this highly toxic and carcinogenic compound. The debate over whether benzene is carcinogenic has long since ended, and controversy about the need to protect humans against benzene must not continue. LeNoir A. Claude J ( I 897): On a case of purpura attributed to benzene intoxication. Bull Mcm Soc.Med Hop 3:14:1251-1261. Nicholwn WJ. Landrigan PJ (19x9): Qucuititativc assessment of lives lost due to delay in regulation of wcupational exposure to benzene. Environ Hcalth Perspect 82: I85-189. Rothman N. Li G-L. Doteineci M. Bechtold W, Marti GE. Wang Y-Z. Linet M. Xi L-Q, Lu W. Smith MT. Titenko-Holland N. Zhang I.-P. Blot W. Yin S, Hayes RB (1996): Hematotoxicity amoiig Chinese workers heavily exposed to benzene. A m 1 Ind Med. 29:236-246. Ward E. Homung R. Morris J, Rinsky R, Wild D. Halperin W, Guthrie W (lY96): Risk of low red or white blood cell count rclated t o estimated benzene exposure in a ruhherworker cohort (1940-1975). Am J Ind Med. 29247-251. REFERENCES Delore P. Burgulnano C (1928): Leucemie aigue ell c o w \ de I'intoxication knzenique. Sur I'origine toxique de certaines Icucemies aigues et leurs relations avcc les aneiiiies p v e s . J Med Lynn 9227-233. Yin S-N. Haycs RB, Line1 MS. Li G-L, Dosemeci M. Travis LB. Li C-Y. Zhatig Z-N,Li D-G. Chow W-H, Wacholdcr S. Wang Y-2,Jiang Z-L, Dai T-R, Zhang W-Y. Chao X-J. Ye P-Z, Kou Q-R.Zhang X-C, I.in X-F. Mcng J-F. Ding C-Y. Zho J-S. Blot WJ ( 1996): A colior~study of cancer among henzene-exposed workers in China: Overall results. Am J Ind Med, 29:227-23s. Goldwater LJ (1941): Disturbanccs in the blood following exposure to Young N (1989): Editorial: Benzene and lymphoma. Am J Intl Med. 15: benzol. J Lab Cliii Med 26:957. 495 -498.