FW: [Pharmwaste] Hormesis gets massive data support

Thu Oct 5 11:13:07 EDT 2006

Thanks to Christian Daughton for sending this article - it may have been
posted before, but this is a good review article for non-chemists to gain a
better understanding of PPCPs in the environment.
Laurie

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  

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-----Original Message-----
From: daughton.christian at epamail.epa.gov
[mailto:daughton.christian at epamail.epa.gov] 
Sent: Thursday, October 05, 2006 9:02 AM
To: Tenace, Laurie
Subject: Re: [Pharmwaste] Hormesis gets massive data support

Laurie: Hormesis is always a topic that guarantees active debate among
toxicologists. Calabrese's contributions essentially resurrected this
field after decades of languishing in disrepute.

But with this aside, other aspects of hormesis must be considered before
reaching any conclusions as to whether it could ever impact the
regulatory world. I've briefly summarized some of these concerns in the
attached article (search for "hormesis" to locate the section). The
debate essentially becomes one of perspective, where we need to ask
whether our anthropocentric views of the world are meaningful when
trying to assess absolute risk.

christian daughton

(See attached file: RRJ - Emerging Contaminants manuscript.pdf)
(Embedded image moved to file: pic21138.jpg)

             "Tenace, Laurie"                                           
             <Laurie.Tenace at d                                           
             ep.state.fl.us>                                         To 
             Sent by:                 pharmwaste at lists.dep.state.fl.us  
             pharmwaste-bounc                                        cc 
             es at lists.dep.sta                                           
             te.fl.us                                           Subject 
                                      [Pharmwaste] Hormesis gets        
                                      massive data support              
             10/05/2006 05:43                                           
             AM                                                         

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

Please Note:  Florida has a very broad public records law.  Most written
communications to or from state officials regarding state business are
public
records available to the public and media upon request.  Your e-mail is
communications and may therefore be subject to public disclosure.

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