A QUANTITATIVELY-BASED METHODOLOGY FOR THE EVALUATION OF CHEMICAL HORMESIS

The recent creation of a chemical hormesis database revealed approxima tely 350 studies qualitatively judged to show high, moderate, or low e vidence of hormesis. A quantitative methodology was subsequently devel oped to more rigorously evaluate an experiment's capacity to demonstra te hormesis. Criteria were established and assigned point values based on: 1) the number of experimental doses below the high NOEL (i.e., wi thin the hermetic zone); 2) experimental determination or estimation o f the high NOEL; 3) the statistical significance of the stimulatory re sponse; 4) the magnitude (percentage of control value) of the stimulat ory response; and 5) the reproducibility of data by other studies. Evi dence of hormesis was assessed by comparing the summation of point val ues to point ranges established for six evidence categories: high, mod erate-high, moderate, low-moderate, low, and no-low. Due to the emphas is on rigorous study design and statistical analysis criteria, 53% of the experiments received total scores within the ''low'' evidence cate gory, while only 17% were ranked in the ''high'' and ''moderate-high'' categories. These results reflect the scheme's strengths in that it r ewards studies with 1) statistically significant data; 2) multiple dos es 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 stimula tion with low magnitude of response are penalized). Overall, the prese nt findings are consistent with the more qualitative judgment that che mical hormesis appears to be a highly generalizable phenomenon with re spect to biological model, endpoint, and chemical class.