Benzene immune effects

Polychloro-benzenes, polybromo-benzenes, and dioxins (TCDD) are among these compounds. They were discovered when the analysis techniques improved. Especially the development of GC-MS has contributed to the knowledge of the distribution of these compounds. Effects on humans are the development of chloracne, suppression of the immune system, and some compounds are probably carcinogens (Shaw 1993). As a consequence of the ubiquitous nature of PCBs, humans are exposed via many sources. 

Organic solvents, which induce CYP2E1, are comprised of a few broad chemical classes, including hydrocarbons such as benzene and toluene, halogenated aliphatic compounds such as carbon tetrachloride and dichloroethane, aliphatic alcohols such as ethanol, and hydroxyethers such as 2-methoxyethanol. Industrial solvents are frequently mixtures of several compounds. The most frequent solvent-associated toxicity occurs from occupational exposure. A number of organic solvents have been examined for their effects on the immune system, and the requirement for their bioactivation to produce immunotoxicity has been well established. 

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. 

Other studies have also shown similar effects on immune functions following acute-duration exposure to benzene. These include decreased numbers of circulating leukocytes and decreases in bone marrow cellularity in mice exposed to 100 ppm and higher, 24 hours per day for up to 8 days (Gill et al. 1980) decreased leukocytes and increased leukocyte alkaline phosphatase in rats exposed to 100 ppm for 7 days (Li et al. 1986) decreased leukocytes and bone marrow cellularity in DBA/2 mice exposed to 300 ppm benzene for 2 weeks (Chertkov et al. 1992) and decreased leukocytes in mice exposed to 300 ppm for 10 days (Ward et al. 1985). These studies are more fully described in Section 2.2.1.2. Decreased spleen weight and levels of B- and T-lymphocytes have also been noted in the blood and spleen of mice exposed 6 hours per day to 47-48 ppm of benzene for 7 or 14 days (Aoyama 1986). Decreased thymus weights were also noted at the 48 ppm dose after 14-day exposure (Aoyama 1986). 

Benzene also affects functional immune responses, as indicated by decreased resistance to infectious agents. Pre-exposure to benzene at >30 ppm for 5-12 days increased the bacterial counts in mice on day 4 of infection with Listeria monocytogenes (Rosenthal and Snyder 1985). Recovery of the immune system was noted on day 7. The effects did not occur at 10 ppm. In addition, a concentration-dependent statistically significant depression was noted in T- and B-lymphocyte populations from day 1 through day 7 at 30 ppm and above. B-cells were more sensitive to benzene than were T-cells on a percentage-of-control basis. This indicates a benzene-induced delay in immune response to L. monocytogenes. Concentrations of 200 or 400 ppm for 4-5 weeks (5 days per week) suppressed the primary antibody response to tetanus toxin in mice, but there was no effect at 50 ppm (Stoner et al. 1981). In another intermediate-duration exposure study, no changes were noted in the numbers of splenic B-cells, T-cells, or... 

The most characteristic toxic effect of benzene in both human and animal models is the depression of the bone marrow, leading ultimately to aplastic anemia (Rozen and Snyder 1985 Snyder and Kocsis 1975 Snyder et al. 1993b). Rozen and Snyder (1985) have noted that abnormalities of humoral and cell-mediated immune responses following benzene exposure of C57BL mice by inhalation are presumably caused by a defect in the lymphoid stem cell precursors of both T- and B-lymphocytes. They also observed that bone marrow cellularity and the number of thymic T-cells increased, presumably as a compensatory response in these cell lines in response to benzene exposure. This compensatory proliferation may play a role in the carcinogenic response of C57BL mice to inhaled benzene. 

In its acute stages, benzene toxicity appears to be due primarily to the direct effects of benzene on the central nervous system, whereas the peripheral nervous system appears to be the target following chronic low-level exposures. In addition, because benzene may induce an increase in brain catecholamines, it may also have a secondary effect on the immune system via the hypothalamus-pituitary-adrenal axis (Hsieh et al. 1988b). Increased metabolism of catecholamines can result in increased adrenal corticosteroid levels, which are immunosuppressive (Hsieh et al. 1988b). 

Acute-Duration Exposure. There are reports on the health effects resulting from acute exposure of humans and animals to benzene via the inhalation, oral, and dermal routes. The primary target organs for acute exposure are the hematopoietic system, nervous system, and immune system. Acute effects on the nervous system and immune system are discussed below under Neurotoxicity and Immunotoxicity. Information is also available for levels that cause death in humans (e.g., Cronin 1924 ... 

Aoyama K. 1986. Effects of benzene inhalation on lymphocyte subpopulations and immune response in mice. Toxicol Appl Pharmacol 85 92-101. 

Hsieh GC, Sharma RP, Parker RDR. 1988b. Subclinical effects of groundwater contaminants I. Alteration of humoral and cellular immunity by benzene in CD-I mice. Arch Environ Contain Toxicol 17 151-158. 

McMurry ST, Lochmiller RL, Vestey MR, et al. 1991. Acute effects of benzene and cyclophosphamide exposure on cellular and humoral immunity of cotton rats, Sigmodon hispidus. Bull Environ Contain Toxicol 46(6) 937-945. 

Male C57BL/6J mice (7-8/group) were exposed to benzene (0, 10.2, 31, 100 or 301 ppm) in whole-body dynamic inhalation chambers for 6 hours/day for 6 consecutive days. Control mice were exposed to filtered, conditioned air only. Erythrocyte counts were depressed in C57BL/6 mice only at 100 and 301 ppm. At exposures of 10.2 and 31 ppm, respectively, depressions of the proliferative responses of bone-marrow-derived B-cells and splenic T-cells occurred in C57BL/6J mice without causing a concomitant depression in number of splenic T- or B- cells. Peripheral lymphocyte counts were depressed at all levels. No correlation was made of reduced lymphocytes with general effects. These results demonstrates that short-term inhaled benzene even at low exposure concentrations can cause reduction in certain immune associated processes. 

Chemicals that attack the immune system render the body less capable of responding in times of need. Such chemicals are defined as immunotoxins, and immunotoxicology is the study of adverse health effects that result from the interactions of xenobiotics and the immune systemNumerous individual chemicals, including benzene, PCBs, and dioxins, suppress immune system function in humans and lead to increased incidences and intensities of infectious diseases and cancer. 

The major effect of benzene from long-term (365 days or longer) exposure is on tlie blood. Benzene causes harmful effects on the bone marrow and can cause a decrease in red blood cells leading to anemia. It can also cause excessive bleeding and can affect the immune system, increasing the chance for infection. 

In addition to carcinogenic effects, animal studies have shown the effects of benzene exposure on the immune system. Reid et al. showed a significant decrease in splenic cell proliferation in mice exposed to benzene for 14 days. Experimental animal studies also reported reduced circulating white blood cells, as well as changes in spleen morphology and weight in various experimental animal studies. These experimental animal studies further support the observation from 1913 by Wintemits and Hirschfelder that rabbits exposed to... 

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