Handbook of Solvents - George Wypych - ChemTech - Ventech!

1366 Nachman Brautbar
mortality ratio for leukemia and multiple myeloma were increased significantly. The investigators
of this study concluded that there is a quantitative association between benzene exposure
and development of leukemia. Wong 44 evaluated a mortality study of chemical
workers occupationally exposed to benzene and found a significantly increased risk for
lymphohematopoietic malignancies. Linet et al. 45 studied hematopoietic malignancies and
related disorders among benzene exposed workers in China and showed a wide spectrum of
hematopoietic malignancies.
Song-Nian Yin et al. 46 in a cohort study of cancer among benzene exposed workers in
China, studied workers employed in a variety of occupations and showed a statistically significant
increased deaths among benzene exposed subjects for leukemia, malignant lymphoma,
neoplastic diseases of the blood, and other malignancies. The rates were
significantly elevated for the incidence of lymphohematopoietic malignancies risk ratio of
2.6, malignant lymphoma risk ratio of 3.5, and acute leukemia risk ratio 2.6. A significant
excess risk was also found for aplastic anemia and myelodysplastic syndrome. These investigators
concluded that employment in benzene exposure occupations is associated with a
wide spectrum of myelogenous and lymphatic malignant diseases and related disorders of
the hematopoietic lymphatic system.
Hayes et al. 47 in one of the largest epidemiological studies on benzene exposure,
showed a wide spectrum of hematological neoplasms and their related disorders in humans.
The risk for these conditions is elevated at average benzene exposure levels of less than 10
ppm. These investigators further concluded that the pattern of benzene exposure appears to
be important in determining the risk of developing specific diseases. Wong 48 studied a cohort
of 7,676 male chemical workers from seven plants who were occupationally exposed
continuously or intermittently to benzene for at least 6 months, and compared them to a
group of male chemical workers from the same plant who had been employed for at least 6
months during the same period but were never occupationally exposed to benzene and
showed a significantly increased risk of lymphohematopoietic malignancies.
In experimental animals benzene has been shown to be associated, in rats, with cancers
of zymbal gland, oral cavity, nasal cavities, skin, forestomach, mammary gland,
Harderian gland, preputial glands, ovary, uterus, angiosarcoma of liver, hemolymphoreticular
neoplasia, lung cancers and leukemia. 49 The ability of benzene metabolites to effect
lymphocytic growth and function in vitro, is shown to correlate with the oxidation capacity
and concentration of the metabolites at the target site. Benzene also effects
macrophages, as well as lymphocytes. 36,50,51 Kalf and Smith 52,53 have shown that benzene exposure
reduces the ability of marrow stromal cells to support normal stem cell differentiation.
From these experimental animal studies, and in vitro studies a wide range of bone
marrow effects of benzene metabolites is shown. It has been concluded that the
hematotoxicity of benzene depends on the breakdown metabolites and can effect the stem
cell at any point in time, for instance myeloid, erythroid, macrophages, lymphocytic stem
cells, and therefore benzene has been named as a pleural potential stem cell toxicant. 54
In addition to carcinogenic effects, animal studies have shown the effects of benzene
exposure on the immune system. Reid et al. 55 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. 54 These experimental animal studies further
support the observation from 1913 by Winternits and Hirschfelder 56 that rabbits exposed to