Benzene leukemia

The lARC has concluded that epidemiological studies have established the relationship between benzene exposure and the development of acute myelogenous leukemia and that there is sufficient evidence that benzene is carcinogenic to humans. Although a benzene-leukemia association has been made, the exact shape of the dose-response curve and/or the existence of a threshold for the response is unknown and has been the source of speculation and controversy. Some risk assessments suggest exponential increases in relative risk (of leukemias) with increasing cumulative exposure to benzene. At low levels of exposure, however, a small increase in leukemia mortality cannot be distinguished from a no-risk situation. In addition to cumulative dose other factors such as multiple solvent exposure, familial connection, and individual sus-... 

Certain chemicals cause cancer of the internal organs and systems of the body. Tar, bitumen, anthracene, and their compounds, products, and residues can cause cancers of the skin. Widely used chemicals that are carcinogens are vinyl chloride (liver cancer), benzene (leukemia), formaldehyde (nasal cancer), butadiene, ethyleneamine, trichloroethylene, and a long list of others. Many of these were found only after extensive worker complaints and analytical tests. 

At one time benzene was widely used as a solvent This use virtually disappeared when statistical studies revealed an increased incidence of leukemia among workers exposed to atmospheric levels of benzene as low as 1 ppm Toluene has replaced benzene as an inexpensive organic solvent because it has similar solvent properties but has not been determined to be carcinogenic m the cell systems and at the dose levels that benzene is... 

Neither the mechanism by which benzene damages bone marrow nor its role in the leukemia process are well understood. It is generally beheved that the toxic factor(s) is a metaboHte of benzene (107). Benzene is oxidized in the fiver to phenol [108-95-2] as the primary metabolite with hydroquinone [123-31-9] catechol [120-80-9] muconic acid [505-70-4] and 1,2,4-trihydroxybenzene [533-73-3] as significant secondary metabolites (108). Although the identity of the actual toxic metabolite or combination of metabolites responsible for the hematological abnormalities is not known, evidence suggests that benzene oxide, hydroquinone, benzoquinone, or muconic acid derivatives are possibly the ultimate carcinogenic species (96,103,107—112). 

Aplastic anemia and leukemia are not the only health effects ascribed to benzene exposure. A number of recent studies have associated benzene exposure with chromosomal changes (aberrations) (118). Other studies have shown abnormalities in porphyrin metabolism and decrease in leucocyte alkaline phosphatase activity in apparendy healthy workers exposed to 10—20 ppm benzene (119,120). Increases in leukoagglutinins, as well as increases in blood fibrinolytic activity, have also been reported and are believed to be responsible for the persistent hemorrhages in chronic benzene poisoning (121,122). 

Treatment for chronic benzene poisoning is supportive and symptomatic, with chemotherapy and bone marrow transplants as therapeutic agents for leukemia and aplastic anemia (127). 

For example, exposure to the air toxin benzene catr increase the risk of getting myelogenous leukemia or aplastic anemia, while exposure to ground-level ozone can cause a 15 to 20 percent decrease in lung capacity in some healthy adults. 

Benzene, C6H6, used in the manufacture of plastics, is a carcinogen affecting the bone marrow. Long-term exposure has been shown to cause leukemia and other blood disorders. The combustion of benzene is given by the following equation ... 

NADPH quinone oxido-reductase 1 Pro187Ser variant occurring with about 5% frequency is functionally almost completely deficient. Impaired activity associated with benzene toxicity and cancer chemotherapy induced leukemia. 

Carcinogenic agents include chemicals in the environment, such as aniline and benzene, which are associated with the development of bladder cancer and leukemia, respectively. Environmental factors, such as excessive sun exposure, also may result in cancer. Viruses, including the human papilloma virus and hepatitis B, maybe associated with the development of cancer. Some of the chemotherapy agents cause secondary cancers after therapy has been completed. Numerous factors may contribute to the development of cancer. 

Although benzene has recently come under increasing control because of its alleged role in leukemia and other neoplastic diseases, in past years it has been widely dispersed in commercial uses and has entered the environment through many routes. In 1977, SRI attempted to characterize "Human Exposures to Atmospheric Benzene" (1). Most of the following examples come from that report, even though several later studies have updated and refined that work, and recent events have changed exposure patterns. 

Acute MI (myocardial infarction), 5 107 antianginal agents for, 5 110t and coronary arterial thrombosis, 5 170 Acute myelogenous leukemia (AML), and benzene exposure, 3 616 Acute oral toxicity... 

In addition, as we shall see again later, some solvents such as benzene, when contacted over prolonged periods, have the special capacity of acting to destroy the bone marrow that manufactures red blood cells or to stimulate the production of white blood cells in the form of a type of blood cancer known as leukemia. And still others, such as hexane and methyl butyl ketone (MBK), have the capacity to damage the nerve supply to the muscles of the legs, in particular. 

Some authorities suggest that still another condition can be found in some persons. This is a form of cancer of the white blood cells known as leukemia. Leukemia, which can occur in various forms depending on the cells involved, is an excessive overdevelopment of white blood cells. It is as though, while preventing the manufacture of red cells, the benzene in the bone marrow actually stimulates the manufacture of white cells to grossly excessive amounts, which will ultimately kill the person exposed. 

Benzene was linked to an abnormally high rate of leukemia increased concern with benzene use in industry. 

Figure 6.1 Relative risk of leukemia associated with occupational benzene exposure.

Individuals working in a petroleum refinery are routinely exposed, over the course of an eight-hour work day, to the volatile hydrocarbon benzene, a constituent of petroleum that has been established through epidemiology studies, in quite different occupational situations, as a cause of human leukemia. Is it possible to understand whether and to what extent these specific, unstudied refinery workers are at risk of developing leukemia ... 

Let us assume that Mr. Z does indeed have leukemia. For many conditions claimed by plaintiffs, especially those that are highly subjective in nature (headaches, nausea, intermittent skin rashes, insomnia, muscle pain), a similarly objective diagnosis may not be possible this creates many problems in causation evaluation which we shall not try to cope with here. But to evaluate the likelihood that Mr. Z s leukemia was caused by one or more water contaminants, it will be necessary to determine whether there is evidence in the scientific literature that is sufficient to establish a causal link (in the sense, for example, described by lARC and discussed in Chapter 6) between exposure to any one of those contaminants and leukemia. This evaluation is referred to as an analysis of general causation. Thus, it is directed at the question of whether one or more of the chemicals to which Mr. Z was exposed is known, in a general sense, to be a cause of leukemia. If benzene is, for example, one of the chemicals found in Mr. Z s well, and it can be established that he consumed water containing benzene, then we could conclude that general causation is established. 

Let us assume that enough information is available regarding the levels of benzene in Mr. Z s well, the number of years he consumed the water, and even his water consumption rate, to derive a reasonably accurate estimate of his cumulative exposure from this source. The epidemiologists and biostatisticians carefully evaluate the dose-response data from the published epidemiology studies used as the basis for classifying benzene as a cause of leukemia. Further assume that we learn from this evaluation that Mr. Z incurred a cumulative benzene exposure approximately equivalent to the cumulative exposure that was found to cause a three-fold excess risk of leukemia in the occupational studies of benzene exposure. A relative risk of three. 

Toxicology. Acute benzene exposure causes central nervous system depression chronic exposure causes bone marrow depression leading to aplastic anemia and is also associated with an increased incidence of leukemia. 

Numerous case reports and epidemiological studies suggest a leukemogenic action of benzene in humans—the leukemia tending to be acute and myeloblastic in type, often following aplastic changes in the bone marrow. Acute myelocytic leukemia may be preceded by myelodysplastic syndrome, a preleukemic state characterized by abnormal marrow architecture, inadequate hematopoiesis, and many cells with chromosome damage." Benzene may also induce chronic types of leukemia. ... 

One study indicated a fivefold excess of all leukemias and a tenfold excess of myelo-monocytic leukemia among benzene-exposed workers as compared with the US Caucasian male population. Among shoemakers chronically exposed to benzene, the annual incidence of leukemia was 13.5 per 100,000, whereas the incidence in the general population was 6 per 100,000." Four cases of acute leukemia were reported in shoemakers exposed to concentrations of benzene up to 210 ppm for 6-14 years two of the four had aplastic anemia before leukemia three of the four cases of leukemia were of the acute myeloblastic type the fourth patient developed thrombocythemia in the second year after an episode of aplastic anemia, and acute monocytic leukemia developed later. ... 

Persons with aplastic anemia due to benzene exposure have been found to be at a much greater risk for developing leukemias. A follow-up of 51 benzene-exposed workers with pancytopenia revealed 13 cases of leukemia. The cumulative incidence of leukemia among individuals with clinically ascertained benzene hemopathy has ranged from 10% to 17% in various studies. ... 

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