An extended commentary on "Models and regulatory considerations for transient temperature rise during diagnostic...

This commentary addresses the matter of misinterpretation of thermal dose as discussed by Herman and Harris (2002), and shows that the thermal doses they would consider as ineffective (i.e., "safe") for producing a hyperthermia-induced teratologic effect, can be highly effective ones. The matter of whether or not thermal thresholds exist for teratologic effects is reviewed. There are only opinions about thresholds. The critical experiments for ascertaining whether or not a threshold exists have not been undertaken. A power computation illustrates the requisite sample sizes (litters, fetuses) for undertaking an experimental test of whether the hyperthermic teratologic response in rats is characterized by threshold or simple linearity kinetics.