Chemical of Current Interest-Benzene

Abstract

Benzene is one of the world's major commodity chemicals. It is derived from petroleum and coal and is used both as a solvent and as a starting material in chemical syntheses. The numerous indus trial uses of benzene over the last century need not be recounted here, but the most recent addition to the list of uses of benzene is as a component in a mixture of aromatic compounds added to gaso line for the purpose of replacing lead compounds as anti-knock ingredients.

The best known and longest recognized toxic effect of benzene is the depression of bone marrow function seen in occupationally exposed individuals. These people have been found to display ane mia, leucopenia, and/or thrombocytopenia. When pancytopenia, i.e., the simultaneous depression of all three cell types, occurs and is accompanied by bone marrow necrosis, the syndrome is called aplastic anemia. In addition to observing this decrease in humans and relating it to benzene exposure, it has been possible to establish animal models which mimic the human disease. The result has been considerable scientific investigation into the mechanism of benzene toxicity.

Although the association between benzene exposure and aplastic anemia has been recognized and accepted throughout most of this century, it is only recently that leukemia, particularly of the acute myelogenous type, has been related to benzene. The acceptance of benzene as an etiological agent in aplastic anemia in large measure derives from our ability to reproduce the disease in most animals treated with sufficiently high doses of benzene over the necessary time period. Unfortunately, despite extensive efforts in several laboratories, it has not been possible to establish a reproducible, reliable model for the study of benzene-induced leukemia. The recent demonstration that several animals exposed to benzene either by inhalation or in the drinking water during studies by Drs. B. Goldstein and C. Maltoni suggests that such a model may be forthcoming. Nevertheless, at this time it is not clear whether bone marrow damage of the type that leads to aplastic anemia is required for the development of leukemia.

Most studies of benzene toxicity have involved dosing animals with benzene either by inhalation or by injection, using high doses to ensure a toxic response. Very few studies have concentrated on the oral route of administration and none have concentrated on admin istering benzene by mouth at the low doses occasionally detected in drinking water. Thus, the evaluation of benzene toxicity in this report takes advantage of the benzene literature as it currently exists and cannot directly answer the questions posed by the prob lem of benzene in drinking water, although it is known that ben zene can be absorbed via the GI tract. Nevertheless, there has not been a demonstation showing that bone marrow depression by benzene can be avoided by selecting an alternate route of adminis tration.

The study will summarize the exposure of the population to ben zene with emphasis on exposure through water. The toxicology of benzene in animals will be reviewed and the problem of attempts to develop an animal model for benzene-induced leukemia will be covered. Emphasis will be given to a discussion of modern theories on the mechanism of benzene induced toxicity and the role played by benzene metabolism. A summary of studies of potential mutagenicity and teratogenicity is included. The extensive literature on both the toxicity and carcinogenicity effects of benzene in humans is described. Finally, a section on carcinogenic risk assess ment has been prepared.