Metabolic Correlates of Benzene Toxicity
The basic concept that underlies the work presented in this and the preceding volume of this series (Jollow et al., 1977) is that the toxicity of many chemicals is seen only after metabolic activation of the original chemical to a more toxic form. Several lines of evidence indicate that benzene also must be metabolically activated in order to exert its characteristic toxicity on bone marrow. Most of the hydroxylated benzene metabolites known today had been described earlier by Parke and Williams (1953). These authors found phenol, catechol, hydroquinone, resorcinol and some trihydroxylated derivatives in the urine of rabbits given 14C-benzene; they suggested some of these may be the toxic metabolite(s). Dustin (1950) reported that di- and trihydroxylated benzenes probably act in their quinone forms to inhibit mitosis. Nomiyama (1965) treated rats with phenol, phenylsulfate, pyrocatechol, hydroquinone, hydroxyhydroquinone and other metabolites of benzene and reported that only catechol caused a reduction in circulating leukocytes. He reasoned that catechol was the toxic metabolite. Andrews et al. (1977) found that in mice given benzene by subcutaneous injection the concentrations of benzene metabolites in the bone marrow exceeded those in blood by a factor of ten. This was the highest organ to blood ratio found when comparing other organs with marrow. Similar data demonstrating sequestration of benzene metabolites in bone marrow were obtained by Rickert et al. (1979) who administered the benzene by inhalation. Andrews et al. (1977) also found that toluene inhibited benzene metabolism competitively, reducing benzene metabolite levels in urine and in the bone marrow and protecting the animals against benzene-induced bone marrow depression. It may be concluded on the basis of these and other related observations that benzene toxicity is due to the formation of a toxic metabolite of benzene.
KeywordsToxic Metabolite Urinary Metabolite Swiss Albino Mouse Ethereal Sulfate Bone Marrow Depression
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