p-dioxin (TCDD)-like by the World Health Organization (WHO) (van den Berg et al. 1998). The toxic potency of each of these DLCs (their TEFs) is expressed relative to that of TCDD (also referred to as dioxin), the most potent member of this chemical class (Part III, Table 1.3, p. 1-20). These chemicals are classified as DLCs, given their similarity in chemical structure and physiochemical properties, their ability to invoke a common battery of toxic responses by a common aromatic hydrocarbon receptor (AHR)–dependent mechanism in vivo, and their ability to be persistent environmentally and to bioaccumulate. The lack of inclusion of the eight mono-ortho PCBs previously assigned TEFs by WHO in the Reassessment at the present time is due to concerns that the previously reported activity of many of these chemicals might have been primarily or partially due to a dioxin-like PCB contaminant (PCB126) present in these mono-ortho PCB preparations (DeVito et al. 2003). Although some AHR-dependent toxic effects have been observed with mono-ortho PCBs prepared by methods that should not produce the more toxic DLCs, it remains to be determined whether most of the reported toxicological effects and resulting relative potency (REP) values of these chemicals are due to contaminants, mono-ortho PCBs, or both. Given this uncertainty and the fact that reanalysis of the mono-ortho PCBs as pure compounds is currently being reexamined, they were not included in the list of relevant DLCs for consideration in the Reassessment. Once these issues are resolved, the mono-ortho PCBs should be considered in a follow-up to the Reassessment if they are documented to produce AHR-dependent toxic effects.

MAJOR ISSUES, ASSUMPTIONS, AND UNCERTAINTIES

The relative toxicological and biological potency of a complex mixture is assessed by the TEF approach. Current TEFs are “order-of-magnitude” qualitative values for dioxins, other than TCDD, and DLCs that were established by a WHO expert scientific panel that examined a large scientific database of REP estimates from in vivo and in vitro studies of the biochemical and toxic effects. In the TEF approach, the concentration of the individual compound present in the mixture (determined by instrumental analysis) are multiplied by their specific TEF value, and the sum is expressed as the TCDD toxic equivalent quotient (TEQ). Summation of the calculated TEQs for all active TCDD-related compounds in a sample extract yields the total TEQ for the specific sample extract. Numerous assumptions underlie the use of the TEF/TEQ approach; these have been well delineated, and the major aspects are discussed in detail in the Reassessment (Part II, Chapter 9, and Part III, Chapter 1, section 1.2). These assumptions and uncertainties are described and discussed below.



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