Hormesis Is Biology, Not Religion
Should hormesis, as Thayer et al. (2006) implied
in the title of their letter in the November 2006 issue of Environmental
Health Perspectives, be dismissed by scientists, regulators, and
others as simply a new faith-based religion? No. Hormesis is a data-based
biological reality, one that challenges the low-dose assumptions that
currently drive risk assessment processes used by regulatory and public
health agencies worldwide.
As we discussed in our recent commentary (Cook and
Calabrese 2006), we believe that default assumptions, however well intentioned,
should not trump data in the formulation of public health policy. Published
scientific information supporting the hormetic nonmonotonic dose–response
curve is extensive. The most recent comes from an article based on a
large National Cancer Institute antitumor drug screening database (Calabrese
et al. 2006), which reports that effects at low-level exposures are
inconsistent with the threshold model and supportive of the hormetic
model.
We believe the current regulatory mandated approach
of narrowly gathering effect data at high doses of exposure and then
dogmatically imputing an excess burden of harmful outcomes monotonically
down to and below the markedly lower levels that actually occur in the
environment is wrong. This approach is wrong because it censors the
observations that can be considered (only high-dose adverse effects
and often just the worst-case sentinel effect) and requires the use
of nonscientific assumptions that are either untested or untestable.
The hormetic model addresses both of those shortcomings. It encourages
the collection of data across a broader range of dose and thereby allows
evaluation of both risks and benefits (specific and holistic) that would
occur at these lower levels. In addition, findings based on the hormesis
model are subject to tests using empirical data.
Without evidence, Thayer et al. (2006) argued that
we were wrong to suggest that public health might be better served by
setting exposure standards at levels using data collected based on the
hormetic model. We strongly disagree. With the additional information,
we believe policies could be developed that would not only prevent excess
disease or death over background but also promote better health, quite
possibly for both the general public and more sensitive subgroups.
Although we differ with Thayer et al. (2006) on
a number of points, we all seem to agree that hormesis exists. Building
on that consensus, perhaps we all can also agree with the perspective
recently presented by Rietjens and Alink (2006): the discipline of toxicology
should refocus its efforts to better address the regulatory issues of
low-dose effects and risk–benefit analysis.
R.C. occasionally consults with Dow Corning on
issues unrelated to environmental regulations. E.J.C. declares no competing
financial interests. Ralph R. Cook RRC Consulting, LLC Midland, Michigan E-mail: ralphrcook@chartermi.net Edward J. Calabrese School of Public Health Environmental Health Sciences Program University of Massachusetts Amherst, Massachusetts E-mail: edwardc@schoolph.umass.edu
Ralph R. Cook
RRC Consulting, LLC
Midland, Michigan
Edward J. Calabrese
School of Public Health
Environmental Health Sciences Program
University of Massachusetts
Amherst, Massachusetts
Reference
Calabrese EJ, Staudenmayer JW, Stanek EJ III, Hoffman
GR. 2006. Hormesis outperforms threshold model in NCI anti-tumor drug
screening database. Toxicol Sci doi: 10.1093/toxsci/kfl098 [Online 1
September 2006].
Cook RR, Calabrese EJ. 2006. The importance of hormesis
to public health. Environ Health Perspect 114:1631–1635.
Rietjens IMCM, Alink GM. 2006. Future of toxicology—low-dose
toxicology and risk–benefit analysis. Chem Res Toxicol 19:977–981.
Thayer KA, Melnick R, Burns K, Davis D, Huff J.
2006. Hormesis: a new religion? [Letter]. Environ Health Perspect 114:A632–A633.
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