Risk assessment of PCDDs and PCDFs based on in vitro and in vivo bioassays
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The mechanism of action of PCDDs and PCDFs has been extensively investigated and the results from a multitude of studies support the role of a receptor-mediated process. Initial binding of the PCDD or PCDF ligand to the aryl hydrocarbon (Ah) receptor is necessary but not sufficient for eliciting the diverse biologic and toxic responses elicited by toxic PCDDs and PCDFs. Although the interspecies potencies of PCDDs/PCDFs (eg. 2,3,7,8-TCDD) may vary widely, the structure-activity relationships (SARs) observed for Ah receptor-mediated in vitro and in vivo responses are comparable. This observation leads to 2 important mechanism-based conclusions; namely, 2,3,7,8-TCDD equivalents values (or toxic equivalency factors) can be utilized for risk assessment of individual PCDD and PCDF congeners and simple in vitro (eg., AHH induction in rat hepatoma cells) or in vivo bioassays can be used for risk assessment of PCDD/PCDF mixtures. © 1989.
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