Benzene exposure

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). 

In 1971 the OSHA standard for benzene (20 CFR, Part 1910.0000) adopted a permissible exposure limit (PEL) of 10 ppm benzene measured as an 8-h TWA. In October of 1976 NIOSH updated its earlier criteria document on benzene and recommended that OSHA lower the benzene exposure standard from 10 to 1 ppm. This proposed implementation was blocked by the United States Supreme Court iu 1980 on the basis of iusufficient evidence linking benzene to cancer deaths. By the mid-1980s convincing evidence of the carciuogenicity of benzene appeared through animal studies which justified reconsideration of the 1 ppm PEL (130). 

In the early part of the twentieth century, benzene was used as a universal solvent and degreaser and found widespread use throughout the mbber iadustry iu the manufacture of tires. By the late 1920s, foUowiug reports of deaths due to benzene exposure, it was largely replaced by toluene and ahphatic solvents (131). 

The models in the THERdbASE CD are Chemical Source Release, Instantaneous Emission, Chemical Source Release, Timed Application, Indoor Air (2-Zone), Indoor Air (N-Zone), Exposure Patterns for Chemical Agents, Benzene Exposure Assessment Model (BEAM), Source Ba.sed Exposure Scenario (Inhalation + Dermal), and Film Thickness Based Dermal Dose. 

Table IV COMPARISON OF BENZENE EXPOSURES AMONG SOURCES (1)...

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... 

The model by Medinsky et al. (1995) considered the dosimetry of benzene and its metabolites in bone marrow in order to help explain their hematotoxic and myelotoxic effects. It is well known that none of the metabolites alone produces the effects seen with benzene exposure. Although it is not yet a fully developed PBPK model, this study lays the groundwork for further model development. 

Stommel P, Muller G, Stucker W et al. 1989. Determination of S-phenylmercapturic acid in the urine-An improvement in the biological monitoring of benzene exposure. Carcinogenesis 10 279-282. 

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

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. 

A registry does exist for benzene, a component of fuel oils. More information on the benzene exposure registry can be found in the ATSDR toxicological profile for benzene (ATSDR 1989). 

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. 

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. ... 

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-... 

A relationship between benzene exposure and lymphoma and multiple myeloma is controversial. In one report, a statistically significant increase in deaths from multiple myeloma was found, although the numbers were small. ... 

Tests for phenol levels in urine have been used as an index of benzene exposure urinary phenol concentrations of 200mg/l are indica-... 

Paustenbach DJ, Price PS, Ollison W, et al Reevaluation of benzene exposure for the pliofilm (rubberworker) cohort (1936-1976). J Toxicol Environ Health 36 177-231, 1992... 

Paxton MB, Chinchilli VM, Brett SM, et al Leukemia risk associated with benzene exposure in the pliofilm cohort. II. Risk estimates. Risk Analysis 14 155-161, 1994... 

WalkleyJE, Pagnotto LD, Elkins HB The measurement of phenol in urine as an index of benzene exposure. Am Ind Hyg Assoc 7 22 362-367, 1961... 

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. 

Chronic exposure to much lower levels has been associated with leukemia of several types as well as lymphomas, myeloma, and myelodysplastic syndrome. Recent studies have shown the occurrence of leukemia following exposures as low as 2 ppm-years. The pluripotential bone marrow stem cells appear to be a target of benzene or its metabolites and other stem cells may also be targets. Epidemiologic data confirm a causal association between benzene exposure and an increased incidence of leukemia in workers. Most organizations now classify benzene as a known human carcinogen. 

Gad El Karim, M.M.. Ramanujam, V.M.S. Legator, M.S. (1986) Correlation between the induction of micronuclei in bone marrow by benzene exposure and the excretion of metabolites in urine of CD-I mice. Toxicol, appl. Pharmacol., 85, 464 77... 

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