Toxicological Sciences 63, 149 (2001)
Copyright © 2001 by the Society of Toxicology
Letter
Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003
To the Editor:
A recent Forum article on the harmonization of cancer and noncancer risk assessment summarized the proceedings of a consensus-building workshop (Bogdanffy et al.2001
). While the workshop addressed a range of relevant and important issues necessary to the harmonization process, it did not address the concept of hormesis (i.e., low dose stimulation, high dose inhibition) and how it may provide both a theoretical and practical foundation for the harmonization of cancer and non-cancer risk assessment. The basis of the present dichotomy between the two risk assessment approaches is the long-standing assumption that the response of carcinogens is linear at low doses while noncarcinogens act via a threshold. Hormetic dose-responses are U-shaped or inverted U-shaped depending on the endpoint. These responses are highly generalizable, independent of animal model, chemical class and endpoint, and quite common if the study is appropriately designed. Of particular importance is that the quantitative features of the dose response with respect to amplitude and range of the hormetic response and their relationship to the zero equivalent point (i.e., the highest dose showing a response equal to the control response) for carcinogens and noncarcinogens are remarkably similar. This is the case whether the mechanisms are similar, different, or not determined. If this perspective had been recognized by regulatory agencies in the 1970s and hormetic features of the doseresponse had been incorporated into the risk assessment process, the principle features of cancer and noncancer endpoint harmonization could have been achieved early on. It is hoped that continuing efforts at harmonization will incorporate the concept of hormesis and utilize the substantial data available on this topic (Calabrese and Baldwin, 1997a,b; 2001). A similar recommendation has recently been made by Lave (2001) in his assessment of the public health implications of hormesis.
REFERENCES
Bogdanffy, M. S., Daston, G., Fuastman, E. M., Kimmel, C. A., Kimmel, G. L., Seed, J., and Vu, V. (2001). Harmonization of cancer and noncancer risk assessment: Proceedings of a consensus-building workshop. Toxicol. Sci. 61, 18–31.
Calabrese, E. J., and Baldwin, L. A. (1997a). The dose determines the stimulation (and poison): Development of a chemical hormesis database. Int. J. Toxicol. 16, 545–559.
Calabrese, E. J., and Baldwin, L. A. (1997b). A quantitatively-based methodology for the evaluation of chemical hormesis. Hum. Ecol. Risk Assess. 3, 545–554.
Calabrese, E. J., and Baldwin, L. A. (2001). The frequency of U-shaped dose-responses in the toxicological literature. Toxicol. Sci. 62, 330–338.
Lave, L. B. (2001). Hormesis: Implications for public policy regarding toxicants. Ann. Rev. Public Health 22, 63–67.[Web of Science][Medline]
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