Development of an oral cancer slope factor for Aroclor 1268

Abstract

Rodent cancer bioassays indicate that substantial differences exist among PCB mixtures in terms of tumorigenic response, although no bioassay has been conducted with Aroclor 1268. The USEPA has used data from these studies to develop three sets of PCB cancer slope factors (CSFs) ranging from 0.07 to 2.0 (mg/kg-day) −1. Selection of the appropriate CSF for risk assessment purposes is largely a function of the exposure circumstances rather than the PCB mixture involved. Since the congener composition of Aroclor 1268 differs substantially from that of the predominant PCB mixture (Aroclor 1254) used to derive the CSFs, the validity of applying existing CSFs to Aroclor 1268 is questionable. We have therefore undertaken the task of developing cancer potency estimates specifically for Aroclor 1268. Potency estimation approaches for Aroclor 1268 were based in part on existing potency estimates for other PCB mixtures, coupled with the relative 2,3,7,8-tetrachlorodibenzo- p-dioxin toxic equivalents (TEQ) content and bioaccumulation potential of PCB mixtures. As such, both Ah-dependent and independent mechanisms of tumorigenesis were considered relevant. Both empirical evidence and mechanistic considerations indicate Aroclor 1268 is substantially less toxic and carcinogenic than the PCB mixtures that have been used by the USEPA to develop CSFs. The present analysis indicates that Aroclor 1268 is likely to be 1–2 orders of magnitude less potent than Aroclor 1254 in terms of potential tumorigenicity. Therefore, we suggest an upper-bound cancer potency factor of 0.27 (mg/kg-day) −1 for Aroclor 1268, a value that is 7- to 8-fold lower than the USEPA’s current default, but nonetheless adequately conservative.