Sunday, October 23, 2005

Hormesis - A New Model for Houdini Risk Assessment Developed by the Money Tox Industry

Hormesis is a new model "houdini risk assessment." Houdini risk assessements make a risk disappear, or permit a public health agency to escape from having to do anything difficult.

Hormesis assumes that low doses of toxic materials are therapeutic.

Well known are many therapeutic or health-promoting exposures - for example, Vitamin A or most pharmaceuticals - which are toxic at higher doses. Moderate alcohol consumption associates with much improved mortality experience compared to not drinking at all. Female-related estrogen contributes several extra years of lifespan at the cost of hugely increased risk of dying of breast, ovarian, uterine and cervical cancer.

From this does it follow that agents or exposures toxic at higher doses promote health at lower doses which don't present adverse effects? "Hormetics" argue yes.

This review, available in free full text, helps restore some balance of the money tox literature. Problem here is that compared to the massive carcinogenesis literature, the relevant literature here is nearly every dose response study in the pharamacology and toxicology world.

BrooklynDodger notes that below a no observed effect level, results have a 50/50 chance of reduced effect compared to the NOEL; two dose levels at 25% chance of both being "therapeutic" and 1/8 of a apparent j-shaped exposure-response.

Fundamental Flaws of Hormesis for Public Health Decisions

Kristina A. Thayer,1 Ronald Melnick,1 Kathy Burns,2 Devra Davis,3 and James Huff1
1National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services,Research Triangle Park, North Carolina, USA;, Lexington, Massachusetts, USA; 3H. John Heinz III School of Public Policy & Management, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA

Hormesis (defined operationally as low-dose stimulation, high-dose inhibition) is often used to
promote the notion that while high-level exposures to toxic chemicals could be detrimental to
human health, low-level exposures would be beneficial. Some proponents claim hormesis is an adaptive,
generalizable phenomenon and argue that the default assumption for risk assessments should be
that toxic chemicals induce stimulatory (i.e., “beneficial”) effects at low exposures. In many cases,
nonmonotonic dose–response curves are called hormetic responses even in the absence of any mechanistic
characterization of that response. Use of the term “hormesis,” with its associated descriptors,
distracts from the broader and more important questions regarding the frequency and interpretation
of nonmonotonic dose responses in biological systems. A better understanding of the biological basis
and consequences of nonmonotonic dose–response curves is warranted for evaluating human health
risks. The assumption that hormesis is generally adaptive is an oversimplification of complex biological
processes. Even if certain low-dose effects were sometimes considered beneficial, this should not
influence regulatory decisions to allow increased environmental exposures to toxic and carcinogenic
agents, given factors such as interindividual differences in susceptibility and multiplicity in exposures.
In this commentary we evaluate the hormesis hypothesis and potential adverse consequences
of incorporating low-dose beneficial effects into public health decisions. Key words: biphasic
dose response, hormesis, individual susceptibility, low-dose exposures, nonmonotonic dose response,
nonlinear dose response, public health, regulation, risk assessment. Environ Health Perspect
113:1271–1276 (2005). doi:10.1289/ehp.7811 available via [Online 15 June 2005]

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