Induction of biotransformation enzymes by polyhalogenated aromatic hydrocarbons (PHAHs):potential impact on animal physiology and health

Abstract

Biotransformation and its role in the elimination of polyhalogenated aromatic hydrocarbons (PHAHs) has been the subject of many studies from the late seventies onwards. The notion of specific, high affinity interactions of phenolic PHAH metabolites with the plasma transport proteins of thyroid hormone and vitamin A, both in vitro and in vivo, stimulated further research into the possible role of biotransformation in the toxicity of certain PHAHs such as PCBs. Currently, phenolic metabolites of PCBs and related compounds have been identified as major metabolites in blood plasma of e.g. grey seals (Halichoerus grypus) and humans with background environmental exposure to these chemicals. The concentrations of the hydroxy-PCBs were in the same range as the most persistent parent congeners, such as PCB 153, 138 and 180. These phenolic metabolites were found to possess a specific range of biological activities, which differed from the parent compounds. Another potential adverse effect associated with persistent induction of biotransformation enzymes, like UDP-glucuronyl transferases (UGTs) by PHAHs, is a long-term enhanced elimination of several important endogenous ligands such as vitamin A and thyroid hormones. Reduced levels of vitamin A and thyroid hormones have been reported in most experimental animal and wildlife species exposed to PHAHs. The recent observation of the accumulation of high levels of phenolic PCB metabolites in blood and brain of late gestational rat foetuses, in parallel with reductions in both vitamin A and thyroid hormone levels, suggests that these metabolites may play an important role in the observed developmental toxicity of PHAHs