Response: Hexachlorobenzene

There is no PF for TCDD currently available in the Integrated Risk Information Service database (3). However, the PF originally derived from the aforementioned study was 156,000 mg/kg/day and may be modified downward to approximately 100,000 mg/kg/day, based on reinterpretation of histopathologic data. Applying van Birgelen's TEF to these values would suggest a PF for the carcinogenic action of HCB (under the linearized multistage assumptions) to be approximately 10-16 mg/kg/day, or about an order of magnitude more potent than is suggested by the in vivo data. It is possible that the difference lies in pharmacokinetic or pharmacodynamic factors that exist in the whole animal, which cannot be captured in cellular assays. As van Birgelen points out (1), the World Health Organization indicates a preference for long-term in vivo studies over in vitro measures when setting a TEF (5). The HCB example illustrates the extreme caution that should be exercised when applying a TEF based solely on in vitro information, particularly when major public health claims are being made.