Mechanisms by Which Chemicals Produce Toxicity

Increased clearance of steroid hormones due to induction of hepatic biotransformation enzymes following chemical exposure often has been cited as a possible mechanism by which toxicants could lower circulating testosterone or 17/3-estradiol levels. While enhanced clearance of sex steroids has been demonstrated following chemical exposure and induction of hepatic biotransformation enzymes, elegant feedback control mechanisms tend to ensure that more hormone is produced and homeostasis is maintained (Figure 17.2). Enhanced clearance of sex steroids can contribute to endocrine disruption if the toxicity also results in impaired hormone synthesis (i.e., gonadal toxicity or interference with the feedback control of hormone synthesis). 2,3,7,8-Tetrachlorodibenzodioxin appears to lower circulating sex steroid levels via this dual effect. 

Fibers that persist within the lung or the mesothelium are capable of producing fibrogenic and tumorigenic effects in these tissues. Although the precise mechanisms by which asbestos fibers cause toxic injury have not been determined, data are available that indicate that both direct interaction between fibers and cellular components and cell-mediated pathways may be involved. In addition, the physical-chemical nature of the fiber appears to be an important determinant of toxicity. Though the various mechanisms are likely to interact extensively, they will be discussed individually below. 

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