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Benzene is classified as a known human carcinogen by the EPA, IARC and NTP. In 1980 benzene was listed in the the National Toxicology Program’s First Annual Report on Carcinogens. (NTP) Benzene is a bone marrow suppressant. The effects of benzene on bone marrow can range from mild and reversible to deadly. The main cancer associated with long term exposure to high levels of benzene in the air is acute myelogenous leukemia: AML. (Toxfaqs, 2007)
Although benzene is listed as the carcinogenic agent, it is actually the metabolites of benzene that are the actual culprits in the suppression of and damage to bone marrow. Benzene is first metabolized in the liver via cytochrome P450 to benzene oxide. Benzene oxide is then converted to a number of metabolites such as phenol, hydroquinone, muconic acid, muconaldehyde, catechol, and trihydroxy benzene. Hydroquinone and muconaldehyde can interfere at many points with the production of blood in the bone marrow. This inefficient production of red blood cells can lead to several blood disorders ranging from anemia to preleukemia and if unchecked, leukemia. Once in the bone marrow, phenolic metabolites of benzene can be further metabolized to form free radicals. These free radicals have the ability to damage bone marrow and lead to cancer, namely AML. (Williams et al., 2000, pp. 102-103)
The population most at risk for adverse health effects from benzene are those who are exposed to benzene in industrial settings. The hematotoxic effects of benzene, including benzenes causal role in AML, have been well documented in several case studies the most notable being the Ohio Pliofilm workers of the 1940’s and 1950’s. The pliofilm fim cohort is of significant importance because the work histories of the workers was well documented, workers were minimally exposed to other carcinogenic chemicals (thus reducing confounding) and the workers were exposed to a wide range of benzene levels. (Toxicological, 2007)
Pliofilm is a thin transparent sheet of chlorinated rubber used for packaging that was produced by the Goodyear Tire and Rubber Company at three different plants in Ohio throughout the twentieth century. Benzene was used on the “wetside” of the plant in the precasting phase of Pliofilm production. Those who worked on the “wetside” part of production were the ones who had direct exposure to benzene and included in the study. Initial results were published in 1987 with a followup based on six years of additional data published in 1996. (Paxton, 1996)
The following table (Paxton, 1996) compares the findings between the two:
As can be seen by the results, the observed noncancer deaths from nonmalignant diseases of the blood and blood forming organs (bone marrow) did not change from 1981to 1987. However, what is significant about the data is that the expected deaths from noncancer blood disorders were 4.65 (1981) and 3.31(1987) times higher for those exposed to benzene than for those who were not. This data is supportive of the noncancerous hematotoxic effects of benzene.
Observed total cancer deaths for 1981 (72) were not statistically higher than the expected deaths (70.88) as can be seen in the Standard Mortaility Ratio of 1.02. However, it is when the deaths are broken down by types of cancer that a suspected role of benzene in the development of hematological malignacies becomes apparent. Fifteen deaths from lymphatic and hematopoietic cancers were observed compared to 6.93 expected with a Standard Mortaility Ratio of 2.16 and a Confidence Interval of 1.21-3.57 (95%). Of the other cancers listed, only male genital organs and “other and unspecified” types of cancers had higher observed than expected rates. However, in both incidents, the range of Confidence Intervals included 1 which indicate that exposure to benzene could not be statistically linked one way or another to these results.
Six years later, once again it is when the deaths from cancer are broken down by type that the observed deaths (21) from lymphatic and hematopoietic cancers far exceed the expected deaths (9.51). The Standard Mortality Ratio is slightly higher at 2.21. The 95% Confidence Interval is slighlty narrower (ranging from 1.37-3.38) bolstering the credibility of the data from 1981.
References:
11th Report on Carcinogens: Benzene. (2009, February 13). Retrieved March 19, 2009, from National Toxicology Program Department of Health and Human Services website: http://ntp.niehs.nih.gov/index.cfm?objectid=32BA9724-F1F6-975E-7FCE50709CB4C932
Paxton, M.B. (1996, December). Leukemia risk associated with benzene exposure in the pliofilm cohort. Environmental Health Perspectives, 104 (6), 1431-1436. Retrieved March 19, 2009, from PubMed Central: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1469754
ToxFAQs for benzene. (2007, October 5). Retrieved March 19, 2009, from Department of Health and Human Services Agency for Toxic Substances and Disease Registry website: http://www.atsdr.cdc.gov/tfacts3.html
Toxicological profile for benzene. (2007, August). Retrieved March 19, 2009, from Agency for Toxic Substances and Disease Registry website: http://www.atsdr.cdc.gov/toxprofiles/tp3.pdf
Williams, P. L., James R. C., Roberts, S. M., (2000). Principles of toxicology, 2nd edition. United States of America: John Wiley & Sons, Inc.
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