A very low dose of a chemical agent may trigger from an organism the opposite response to a very high dose.

Hormesis is the term for generally-favorable biological responses to low exposures to toxins and other stressors. A pollutant or toxin showing hormesis thus has the opposite effect in small doses than in large doses. Image File history File links My illustration of an example hormetic dose response, done in Macromedia Fireworks. ... Image File history File links My illustration of an example hormetic dose response, done in Macromedia Fireworks. ... This article or section does not cite its references or sources. ... The venom of the black widow spider is a potent latrotoxin. ... The venom of the black widow spider is a potent latrotoxin. ...

As an example, challenging mice with small doses of gamma ray radiation shortly before irradiating them with very high levels of gamma rays actually decreases the likelihood of cancer. There is a similar effect when dioxin is given to rats. Binomial name Mus musculus Linnaeus, 1758 Mus musculus is the common house mouse. ... This article is about electromagnetic radiation. ... For other uses, see Cancer (disambiguation). ... Space-filling model of 2,3,7,8- tetrachlorodibenzo-p-dioxin Structure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) Dioxin is the popular name for the family of halogenated organic compounds, the most common consisting of polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzodioxins (PCDDs). ... Species 50 species; see text *Several subfamilies of Muroids include animals called rats. ...

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. Such environmental factors that would seem to produce positive responses have also been termed "eustress". Toxicology (from the Greek words toxicos and logos [1]) is the study of the adverse effects of chemicals on living organisms [2]. It is the study of symptoms, mechanisms, treatments and detection of poisoning, especially the poisoning of people. ... Dose response is the change in effect on an organism caused by differing levels of exposure to a substance. ... Categories: Possible copyright violations ...

Possible explanation

The biochemical mechanisms by which hormesis works are not well understood. It is conjectured that a low dose challenge with a toxin may jump start certain repair mechanisms in the body, and these mechanisms are efficient enough that they not only neutralize the toxin's effect, but even repair other defects not caused by the toxin. This is similar in principle to viral vector vaccines under development for diseases such as cancer and AIDS. ^{[citation needed]} Viral vectors are a tool commonly used by biologists to deliver genetic material into cells inside a living organism or cultured in vitro. ... A vaccine is an antigenic preparation used to establish immunity to a disease. ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these cells to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ... This article is about the syndrome. ...

A deeper explanation is that low doses interact with genetic signaling systems that upregulate gene expression, whereas high doses cause overt toxicity. This fits well with ideas from the evolution of aging. Aging is not a wearing-out or a failure of the body, but rather a purposeful adaptation, the purpose of which probably has to do with population regulation. The body is programmed to self-destruct, but in times of hardship (when many individuals are dying of external causes) the aging program lets up in order to moderate the death rate. The combination of aging and hormesis acts to level out natural population cycles, by keeping the death rate more constant. Why do almost all living things weaken and die with age? There is not yet agreement in the academic community on a single answer. ...

Policy consequences

Regulatory agencies such as the Environmental Protection Agency (EPA), the Food and Drug Administration (FDA), and the Nuclear Regulatory Commission (NRC) use a linear no-threshold model for carcinogens (including radiation). In the linear model, the assumption is that there is no dosage that has no risk of causing cancer. EPA redirects here. ... The Food and Drug Administration (FDA) is an agency of the United States Department of Health and Human Services and is responsible for regulating food (humans and animal), dietary supplements, drugs (human and animal), cosmetics, medical devices (human and animal) and radiation emitting devices (including non-medical devices), biologics, and... NRC headquarters in Rockville, MD. Nuclear Regulatory Commission (or NRC) is a United States government agency that was established by the Energy Reorganization Act in 1974, and was first opened January 19, 1975. ... The linear no-threshold model or LNTM is a model of the damage cased by ionizing radiation, and particularly the increased risk of cancer. ...

While proponents of hormesis argue that hanging to a hormesis model would likely change exposure standards for these toxins in air, water, food and soil, making the standards less strict, other scientists point out that low dose stimulation can have extremely adverse effects. For example, research by Retha Newbold at the US National Institute of Environmental Health Sciences has shown that relatively high doses of a xenobiotic estrogen, diethylstilbestrol, during fetal development cause weight loss in adulthood, extremely low doses cause grotesque obesity. Similarly, low doses of the phthalate DEHP cause increased allergic responses to allergens, while higher doses have no effect. Low dose stimulation can have profoundly adverse consequences. Wider use of the hormesis model would affect how scientists design and conduct studies and the selection of statistical models that estimate risk. In all likelihood, recognizing that low dose effects can't be predicted from high dose experiments would force a strengthening of public health standards, not their weakening, as hormesis proponents would argue. Layers of Atmosphere (NOAA) Air redirects here. ... Impact of a drop of water. ... Loess field in Germany For the Alternative Metal band, see SOiL. Soil, comprising the pedosphere, is positioned at the interface of the lithosphere with the atmosphere, and hydrosphere. ... The physicist Albert Einstein is probably the most famous scientist of our time. ... A statistical model is used in applied statistics. ...

Consistency of low-dose benefits

While some cases of hormesis show low doses of toxins showing beneficial effects, others show profoundly adverse effects. The key is that low doses show the opposite effect of high doses. There are many examples where low doses cause detrimental effects not seen in high doses.

Hormesis is a subset of the more general case of dose-response curves that are characterized mathematically as being non-monotonic. In non-monotonic dose response curves, the slope of the curve changes sign as the dose changes. This change in sign means, on a practical basis, that high dose experiments cannot predict low dose results. The observation that non-monotonic dose response curves are common violates one of the core assumptions of toxicology, that "the dose makes the poison." Decades of research setting health standards have been premised on this assumption. The prevalence of non-monotonic dose response curves means that many health standards may be too weak.

Known hormetic substances

Opioid analgesics have been shown to have paradoxical effects (increased rather than decreased pain) at extremely small doses, and tiny doses of opioid antagonists are sometimes used to enhance the effects of larger doses of opioid analgesics. ^[1] An opioid is a chemical substance that has a morphine-like action in the body. ... For other uses of painkiller, see painkiller (disambiguation) An analgesic (colloquially known as painkiller) is any member of the diverse group of drugs used to relieve pain. ... Antagonists In medicine and biology, a receptor antagonist is a ligand that inhibits the function of an agonist and inverse agonist for a specific receptor. ...

Alcohol has been shown to be hormetic in preventing heart disease and stroke.^[2] Functional group of an alcohol molecule. ...

Non-acceptance

The hormesis model of dose response is largely not accepted.

The study of hormesis has been best developed, perhaps, in the field of ionizing radiation. The United States-based National Council on Radiation Protection and Measurements (a body commissioned by U.S. Congress) recently released a report written by national experts in the field which rejects hormesis for ionizing radiation [1]. This is done partly for the sake of caution and partly for the lack of contrary evidence. They conclude that the model that is effective at high doses, that radiation's effects should be considered to be proportional to the dose an individual receives, should be used at low doses as well . This report squarely rejects almost all research showing radiation induced hormesis as being flawed in some way (i.e. the cancer a study focuses on does not exist in humans, a clear threshold could not be established in humans, the assumptions are seriously flawed, the hormetic effect is too short to be useful). Radiation hazard symbol. ... The National Council on Radiation Protection and Measurements (NCRP) is a U.S. organization which seeks to formulate and widely disseminate information, guidance and recommendations on radiation protection and measurements which represent the consensus of leading scientific thinking. ... Look up Congress in Wiktionary, the free dictionary. ...

Radiation hormesis is not generally accepted by The International Commission on Radiological Protection (ICRP), its U.S. counterpart, the National Council on Radiation Protection and Measurements (NCRP), the National Research Council Committees on the Biological Effects of Ionizing Radiation (the BEIR Committees), or the U.S. regulatory agencies.^[3]. The notion that hormesis is a widespread or important phenomenon in biological systems is not widely accepted.^[4]

Reasons include:

• No well-documented long-term positive effects.
• Unproveable in an ethical study of humans.
• Counterintuitive result; unless a clear mechanism is established then there is often skepticism about small or marginally significant effects unless these have been independently replicated. On the other hand, there are detailed studies at the level of gene regulation showing that low doses cause effects that can't be predicted from high dose experiments.
• Concern about publication bias; studies that show positive effects are more likely to be published than repeats that fail to show the same effect.
• While some chemicals might indeed have paradoxical effects at low doses, there is no particular reason to expect such effects to be positive. Endocrinologists for decades have documented many non-monotonic dose response curves, so it is not surprising that these 'paradoxical' effects are noted with increasing frequency as toxicologists have begun to focus on contaminants that interfere with hormone action. The logical flaw by proponents of hormesis has been to assume the effects tend to be positive. Most are not.

Ethics is a general term for what is often described as the science (study) of morality. In philosophy, ethical behavior is that which is good or right. ... Publication bias, also called the positive outcome bias, is typically the tendency for researchers to publish experimental results that have a positive result (found something), while consequently not publishing findings which have a negative result (found that something did not happen). ...

See also

• Radiation hormesis
• Petkau effect
• Stochastic resonance
• Arndt-Schulz rule

Radiation hormesis is the theory that low doses of ionizing radiation are beneficial. ... The Petkau effect is an early counterexample to linear-effect assumptions usually made about radiation exposure. ... Stochastic resonance occurs when the signal-to-noise ratio of a nonlinear device is maximized for a moderate value of noise intensity. ... Arndt-Schulz rule or Schulz law is a law (named after Hugo Paul Friedrich Schulz and Rudolf Arndt) concerning the effects of pharmaca or poisons in low, respectively strong concentrations. ...

References

• A large amount of information is available from the BELLE (Biological Effects of Low Level Exposure) website.
• International Hormesis Society

NOTE: An early version of this article was based on the press handout: "Hormesis: Principal Concepts and Take Home Message", by Edward J. Calabrese, Ph.D., University of Massachusetts, from a hormesis panel discussion, Feb 25, 2004, Washington, DC. The St. ... 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD (or CE) era. ... February 2 is the 33rd day of the year in the Gregorian Calendar. ...