Factors affecting the storage and excretion of toxic lipophilic xenobiotics

Abstract

Lipophilic toxins have been introduced into the environment both as functional compounds, such as pesticides, and as industrial waste from incineration or the manufacture of electrical transformer components. Among these substances are compounds that are carcinogenic and that affect the endocrine system. Accidental high exposures of humans to some lipophilic toxins have produced overt disease symptoms including chloracne and altered liver function. These toxic materials have been the recent focus of international effort to reduce or eliminate classes of halogenated hydrocarbons from the environment. Evidence of the widespread distribution of lipophilic toxins in the biosphere has been obtained by analyses of human tissues and human milk. The principal route of entry of lipophilic toxins into humans is through the food chain, and most of them are stored in adipose tissue. A common route of excretion is in bile, but there is also evidence of nonbiliary excretion into the intestine. Enterohepatic circulation of many of these compounds slows their removal from the body. Substances that interrupt the enterohepatic circulation of compounds that enter the intestine by the biliary and nonbiliary routes increase the rate of their removal from the body and reduce their storage half-lives. Reduction in body fat, along with these dietary substances that interrupt enterohepatic circulation, further enhances the excretion rate. Areas for further research include optimizing regimens for body burden reductions, understanding the nature of nonbiliary excretion, and following the effects of tissue redistribution during loss of body fat.