Hormesis has been defined as a dose-response relationship in which there is a stimulatory response at low doses, but an inhibitory response at high doses, resulting in a U- or inverted U-shaped dose response. To assess the proportion of studies satisfying criteria for evidence of hormesis, a database was created from published toxicological literature using rigorous a priori entry and evaluativ...

This paper evaluates procedures relevant to extrapolating from toxicity data in man and animals to Occupational Exposure Limits. It examines effects at or around the "No Observed Adverse Effect Level' (NOAEL) and the magnitude of safety factors which can be applied in developing occupational exposure limits for non-stochastic effects. The relationship between incidence of stochastic effect and ...

Unexpected adverse preclinical findings (APFs) are not infrequently encountered during drug development. Such APFs can be functional disturbances such as QT prolongation, morphological toxicity or carcinogenicity. The latter is of particular concern in conjunction with equivocal genotoxicity results. The toxicologic pathologist plays an important role in recognizing these effects, in helping to...

Two well-documented examples of studies that can be eliminated from the data requirement list without apparent impact on the quality of risk assessment are presented. Database evaluations demonstrated no clear difference in sensitivity between 3-month and 12-month dog studies. From a regulatory perspective, only two compounds were identified in which the NOAEL for the 12-month dog study was mor...

2.0 Points of Departure and Potency Estimates...............................................3 2.1 The Benchmark Dose approach.................................................... 3 2.2 The T25 approach......................................................................7 2.3 Comparing BMD and T25 methodology for use in risk assessment.........8 2.4 The TD50 approach................................