Benzene blood effects

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). 

Other important determinants of the effects of compounds, especially solvents, are their partition coefficients, e.g., blood-tissue partition coefficients, which determine the distribution of the compound in the body. The air-blood partition coefficient is also important for the absorption of a compound because it determines how quickly the compound can be absorbed from the airspace of the lungs into the circulation. An example of a compound that has a high air-blood partition coefficient is trichloroethane (low blood solubility) whereas most organic solvents (e.g., benzene analogues) have low air-blood partition coefficients (high blood solubility). 

Toxic Effects on the Blood-Forming Tissues Reduced formation of erythrocytes and other elements of blood is an indication of damage to the bone marrow. Chemical compounds toxic to the bone marrow may cause pancytopenia, in which the levels of all elements of blood are reduced. Ionizing radiation, benzene, lindane, chlordane, arsenic, chloramphenicol, trinitrotoluene, gold salts, and phenylbutazone all induce pancytopenia. If the damage to the bone marrow is so severe that the production of blood elements is totally inhibited, the disease state is termed aplastic anemia. In the occupational environment, high concentrations of benzene can cause aplastic anemia. 

Methods for Determining Biomarkers of Exposure and Effect. Exposure to 1,4-dichloro-benzene may be evaluated by measuring the levels of this compound in blood, breath, milk, and adipose tissue, and by measuring the level of 2,5-dichlorophenol, a metabolite of 1,4-dichlorobenzene, in urine (Bristol et al. 1982 Erickson et al. 1980 Jan 1983 Langhorst and Nestrick 1979 Pellizzari et al. 1985). Sensitive analytical methods are available for measurements in blood. Development of methods with improved specificity and sensitivity for other tissues and breath would be valuable in identifying individuals with low-level exposure. Development of standardized procedures would permit comparison of data and facilitate the study of correlations between exposure and measured levels biological samples. Interlaboratory studies are also needed to provide better performance data for methods currently in use. 

Blood dyscrasias have been noted in humans acutely and chronically exposed to gasoline, but these effects are most likely due to benzene, and the incidence of these findings has decreased as the benzene content in gasoline has decreased. ... 

Before 1940, most reports on the possible chronic toxicity of xylene also involved exposure to solvents that also contained high percentages of benzene or toluene as well as other compounds. Consequently, the effects attributed to xylene in these reports are questionable. Blood dyscrasias, such as those reportedly caused by benzene exposure, have not been associated with the xylenes. ... 

Benzene, a component of motor fuel that is also widely used as an industrial solvent and as a starting material in organic synthesis, is a hematopoietic toxin. Chronic exposure to benzene vapors leads to pancytopenia, that is, decreased production of all types of blood cells (erythrocytes, leukocytes, and platelets). The long-term effect of benzene exposure is acute leukemia. 

Tardif et al. (1992, 1993 a, 1997) have developed a physiologically based toxicokinetic model for toluene in rats (and humans—see Section 4.1.1). They determined the conditions under which interaction between toluene and xylene(s) occurred during inhalation exposure, leading to increased blood concentrations of these solvents, and decreased levels of the hippurates in urine. Similar metabolic interactions have been observed for toluene and benzene in rats (Purcell et al., 1990) toluene inhibited benzene metabolism more effectively than the reverse. Tardif et al. (1997) also studied the exposure of rats (and humans) to mixtures of toluene, we/a-xylene and ethylbenzene, using their physiologically based pharmacokinetic model the mutual inhibition constants for their metabolism were used for simulation of the human situation. 

Toluene generally resembles benzene closely in its toxicological properties however, it is devoid of benzene s chronic negative effects on blood formation. 

What are the chronic toxicological effects of benzene What kinds of blood abnormalities are caused by benzene exposure How does benzene toxicity affect white cell count How does it affect bone marrow ... 

Benzene causes problems in the blood. People who breathe benzene for long periods may experience harmful effects in the tissues that form blood cells, especially the bone marrow. 

These effects can disrupt normal blood production and cause a decrease in important blood components. A decrease in red blood cells can lead to anemia. Reduction in other components in the blood can cause excessive bleeding. Blood production may return to normal after exposure to benzene stops. Excessive exposure to benzene can be harmful to the immune system, increasing the chance for infection and perhaps lowering the body s defense against cancer. 

The health effects that might occur in humans following long-term exposure to food and water contaminated with benzene are not known. In animals, exposure to food or water contaminated with benzene can damage the blood and the immune system and can even cause cancer. See Chapter 2 for more information on the health effects resulting from benzene exposure. 

Several tests can show if you have been exposed to benzene. Some of these tests may be available at your doctor s office. All of these tests are limited in what they can tell you. The test for measuring benzene in your breath must be done shortly after exposure. This test is not very helpful for detecting very low levels of benzene in your body. Benzene can be measured in your blood. However, since benzene disappears rapidly from the blood, measurements may be accurate only for recent exposures. In the body, benzene is converted to products called metabolites. Certain metabolites of benzene, such as phenol, muconic acid, and S-phenyl-N-acetyl cysteine (PhAC) can be measured in the urine. The amount of phenol in urine has been used to check for benzene exposure in workers. The test is useful only when you are exposed to benzene in air at levels of 10 ppm or greater. However, this test must also be done shortly after exposure, and it is not a reliable indicator of how much benzene you have been exposed to, since phenol is present in the urine from other sources (diet, environment). Measurement of muconic acid or PhAC in the urine is a more sensitive and reliable indicator of benzene exposure. The measurement of benzene in blood or of metabolites in urine cannot be used for making predictions about whether you will experience any harmful health effects. Measurement of all parts of the blood and measurement of bone marrow are used to find benzene exposure and its health effects. 

Aplastic anemia is a more severe effect of benzene and occurs when the bone marrow ceases to function and the stem cells never reach maturity. Depression in bone marrow function occurs in two stages—hyperplasia (increased synthesis of blood cell elements), followed by hypoplasia (decreased synthesis). As the disease progresses, bone marrow function decreases and the bone marrow becomes necrotic and filled with fatty tissue. This myeloblastic dysplasia without acute leukemia has been seen in persons exposed to benzene. Aplastic anemia can progress to a type of leukemia known as acute myelogenous leukemia (Aksoy 1980), which is discussed in Section 2.2.1.8. 

People who were exposed to high levels of benzene vapors in the printing industry also showed severe hematological effects. One study evaluated 332 workers who were exposed to 11-1,060 ppm of benzene for 6 months to 5 years. Detailed blood studies performed on 102 of these workers revealed benzene poisoning in 22 workers characterized by pancytopenia or other clinical signs (Goldwater 1941 ... 

In summary, benzene poisoning results in the development of pancytopenia, a condition characterized by decreased numbers of circulating erythrocytes, leukocytes, and thrombocytes. The potential mechanisms for the development of pancytopenia in humans include the destruction of bone marrow stem cells, the impairment of the differentiation of these cells, and/or the destruction of more mature hematopoietic cell precursors and circulating cells. Furthermore, pancytopenia can result from the combined destruction of the peripheral blood and bone marrow elements. In effect, individuals that develop pancytopenia and have continued exposure to benzene may develop aplastic anemia (i.e., pancytopenia associated with fatty replacement of functional bone marrow) others may exhibit both pancytopenia and bone marrow hyperplasia, a condition that suggests a preleukemic state. The data suggest that individual workers vary in their reactions to benzene. 

Green et al. (1981 b) examined the effect of benzene inhalation on the peripheral blood and bone marrow of CD-I mice following exposures to 0 or 9.6 ppm for 6 hours per day, 5 days per week for 10 weeks (50 days), or to 0 or 302 ppm for 6 hours per day, 5 days per week for 26 weeks. Animals exposed to... 

The peripheral blood and bone marrow were altered in CD-I mice and Sprague-Dawley rats exposed for 91 days (13 weeks) to up to 300 ppm benzene (Ward et al. 1985). Interim sacrifices were performed on days 7, 14, 28, and 56 of exposure. No hematological effects were observed at 1, 10, or 30 ppm. At... 

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