A quantitatively-based methodology for the evaluation of chemical hormesis

The recent creation of a chemical hormesis database revealed approximately 350 studies qualitatively judged to show high, moderate, or low evidence of hormesis. A quantitative methodology was subsequently developed to more rigorously evaluate an experiment's capacity to demonstrate hormesis. Criteria were established and assigned point values based on: 1) the number of experimental doses below the high NOEL (i.e., within the hermetic zone); 2) experimental determination or estimation of the high NOEL; 3) the statistical significance of the stimulatory response; 4) the magnitude (percentage of control value) of the stimulatory response; and 5) the reproducibility of data by other studies. Evidence of hormesis was assessed by comparing the summation of point values to point ranges established for six evidence categories: high, moderate-high, moderate, low-moderate, low, and no-low. Due to the emphasis on rigorous study design and statistical analysis criteria, 53% of the experiments received total scores within the ''low'' evidence category, while only 17% were ranked in the ''high'' and ''moderate-high'' categories. These results reflect the scheme's strengths in that it rewards studies with 1) statistically significant data; 2) multiple doses within the hermetic zone (i.e., below the high NOEL); and 3) a high magnitude of stimulatory response. Future refinements should address limitations of the methodology (e.g., studies showing low dose stimulation with low magnitude of response are penalized). Overall, the present findings are consistent with the more qualitative judgment that chemical hormesis appears to be a highly generalizable phenomenon with respect to biological model, endpoint, and chemical class.