[Pharmwaste] Hormesis gets massive data support

[Tenace, Laurie]

Thought-provoking - might hormesis affect how pharmaceuticals act at the very
low concentrations they are found in water? 

Hormesis defined by Wikepedia: In toxicology, hormesis is a dose response
phenomenon characterized by a low dose stimulation, high dose inhibition,
resulting in either a J-shaped or an inverted U-shaped dose response. A
pollutant or toxin showing hormesis thus has the opposite effect in small
doses than in large doses. (for more, go to
http://en.wikipedia.org/wiki/Hormesis)
 
Hormesis gets massive data support
http://pubs.acs.org/subscribe/journals/esthag-w/2006/oct/science/rr_hormesis.
html

The new theory could overturn scores of environmental regulations.
Humble yeast cells may be shedding new light on the controversial theory of
hormesis. Cancer researchers collected data on 13 strains of yeast,
generating a large database of their responses to different chemicals. For
low doses, those reactions are best explained by hormesis-a nonintuitive
dose-response theory-and not by theories currently used in risk assessment,
according to a new analysis by University of Massachusetts toxicologist
Edward Calabrese and colleagues, published in Toxicological Sciences online
on September 1.

 
Julian Simon
At high doses, potential anticancer drugs inhibit yeast growth, but at low
doses, the same chemicals enhance growth, according to the researchers.
Hormesis [160KB PDF]explains that low doses can have the opposite effect of
high doses, such that chemicals that can have harmful biological effects in
relatively large amounts can have beneficial effects in small quantities.
Calabrese and colleagues have found in scores of recent papers signs that
such behavior may be ubiquitous. But risk assessments and environmental
regulations throughout the world operate on one of two assumptions: either
doses below a toxicological threshold have no adverse effects, or all doses
have similar effects.

This means that hormesis has the potential to overturn some environmental
regulations, and its relevance to such policies has engendered lively debate.
"The proper understanding and utilization of hormesis will do a much better
job of both protecting and promoting public health than the policy-based
defaults that are currently in use," Ralph Cook, a physician with RRC
Consulting, and Calabrese wrote this summer. Not so, argued Kristina Thayer,
a toxicologist with the National Institute of Environmental Health Sciences,
and colleagues last year. "If hormesis were used in the decision-making
process to allow higher exposures to toxic and carcinogenic agents, this
would substantially increase health risks for many, if not most, segments of
the general population," they wrote.

The new analysis is the first to use a single large database to put hormesis
to the test against the threshold model, says Calabrese. "In this single,
detailed data set, we again find that the threshold model fails to predict
the low-dose responses and the hormesis model does," he says.

Calabrese and colleagues analyzed 2189 dose-response curves generated by a
National Cancer Institute investigation that was looking for chemicals that
might make good antitumor drugs. The chemicals include many synthetic and
natural organic compounds as well as inorganic and organometallic chemicals.
Few, if any, industrial compounds appear in the set.

The cancer researchers exposed the 13 different strains of yeast to 5 doses
of each of the chemicals. They looked for compounds that blocked growth in
mutant yeast cells at high doses because these chemicals might also be able
to kill human cancer cells, says Julian Simon, who is a cancer researcher at
the Fred Hutchinson Cancer Research Center and who organized the study.

If hormesis were valid, then these chemicals would make the yeasts grow
better at low doses, the researchers thought. To test this, Calabrese and
colleagues determined the amount that did not affect growth, known as the
benchmark dose. If hormesis applied, then doses lower than the benchmark dose
would be more likely to enhance growth. If the threshold model held, then
these lower doses would have an equal chance of enhancing, inhibiting, or not
perturbing growth. When the researchers compared responses below the
benchmark dose, they found that growth was enhanced. Indeed, they found that
this occurred in most of the responses.

Several toxicologists and statisticians say that Calabrese's team modified
standard procedures for identifying the benchmark dose in their analysis.
Some of these scientists add that the modifications were needed to study such
low doses, whereas others question the statistical methods used in the new
study. "I know that they are trying to find out if this data on aggregate
supports hormesis, but there are ways of doing this that have already been
evaluated in the literature, and this is not one of them," says Christopher
Portier of the National Institute of Environmental Health Sciences about the
mathematical analysis.

Others, including Tony Cox, a biomathematical modeler with research
consultants Cox Associates, describe the work as "important, suggestive, and
provocative." The new paper makes an important contribution to this debate,
notes Cox, who adds, "I believe everyone would benefit from further analysis
of this data set. This would show whether the authors' conclusions are robust
to changes in modeling assumptions."

Calabrese is more certain. "There is little justification to continue to
accept and use the threshold model, and growing evidence to support the
hormesis model," he says. "How often can the threshold model be wrong before
it is questioned and set aside? Reasonable people who care about public
health or even the concept of truth must ask that question." -REBECCA RENNER

Laurie J. Tenace
Environmental Specialist
Florida Department of Environmental Protection
2600 Blair Stone Road, MS 4555
Tallahassee, Florida 32399-2400
PH: (850) 245-8759
FAX: (850) 245-8811
Laurie.Tenace at dep.state.fl.us  
 
view our mercury web pages at: 
http://www.dep.state.fl.us/waste/categories/mercury/default.htm 

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