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ToxSci Advance Access published online on September 1, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl098
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received March 31, 2006
Accepted August 30, 2006

Risk Assessment

Hormesis Outperforms Threshold Model in NCI Anti-tumor Drug Screening Database

Edward J. Calabrese Ph.D. 1 *, John W. Staudenmayer Ph.D. 2, Edward J. Stanek III Ph.D. 3, and George R. Hoffmann Ph.D. 4

1 Department of Public Health, Environmental Health Sciences Program, Morrill I, N344. University of Massachusetts. Amherst, MA 01003; Phone: 413-545-3164, Fax: 413-545-4692
2 Mathematics & Statistics, Lederle Grad. Research Tower, University of Massachusetts, Amherst, MA 01003; Phone: 413-545-0999, Fax: 413-545-1801
3 Department of Biostatistics and Epidemiology, School of Public Health & Health Sciences, Arnold House, University of Massachusetts, Amherst, MA 01003; Phone: 413-545-3812, Fax: 413-545-1645
4 College of the Holy Cross, Biology, O'Neil Hall, 107, Worcester, MA 01610-2395; Phone: 508-793-3416, Fax: 508-793-2696

* To whom correspondence should be addressed.
Edward J. Calabrese, E-mail: edwardc{at}schoolph.umass.edu


  Abstract

Which dose-response model best explains low-dose responses is a critical issue in toxicology, pharmacology, and risk assessment. The present paper utilized the US NCI yeast screening database that contains 56,914 dose-response studies representing the replicated effects of 2,189 chemically diverse possible anti-tumor drugs on cell proliferation in 13 different yeast strains. Multiple evaluation methods indicated that the observed data are inconsistent with the threshold model while supporting the hormetic model. Hormetic response patterns were observed approximately four times more often than would be expected by chance alone. The data call for the rejection of the threshold model for low dose prediction, and they support the hormetic model as the default model for scientific interpretation of low dose toxicological responses.

Keywords: hormesis; threshold; dose-response; yeast; NCI; U-shaped; J-shaped; bell-shaped; risk assessment; carcinogens; chemotherapeutics; cell proliferation; Saccharomyces.
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