Hormesis effect

Toxic action is concentration dependent. For example, phenol can be metabolized at low concentrations but becomes toxic at higher concentrations. These types of actions often lead to the occurrence of a hormesis effect, i.e. the stimulating effect of small doses of a toxicant that is known to be inhibitory at larger concentrations. Toxicant action also depends on the presence of other chemicals in solution (Dutka and Kwan, 1982). 

The second hypothesis states that there is a threshold below which no harm accrues, and, further, that lower doses may even be beneficial. When a toxin at high levels is beneficial at low levels, it is called hormesis. Substances exhibiting hormesis are, for example, vitamin D, selenium, aspirin, table salt, water, and, for plants, fertilizer. There may even be a hormesis effect for low-level radiation because this might provide the stimulus for the heighteued activity of DNA repair mechanisms (Karam, 2003). 

For some toxins it is possible to demonstrate an apparent improvement in functional response at levels of exposure which are below a threshold. This effect, which has been termed hormesis , is most effectively demonstrated in the consistently improved longevity of animals whose caloric intake is restricted rather than allowing them to feed ad lib (Tannenbaum, 1942). Clearly in this instance, the observed effects are the result of exposure to a complex mixture of chemicals whose metabolism determines the total amount of energy available to the organism. But it is also possible to show similar effects when single chemicals such as alcohol (Maclure, 1993), or caffeic acid (Lutz et al., 1997) are administered, as well as for more toxic chemicals such as arsenic (Pisciotto and Graziano, 1980) or even tetrachloro-p-dibenzodioxin (TCDD) ( Huff et al., 1994) when administered at very low doses. It is possible that there are toxins that effect a modest, reversible disruption in homeostasis which results in an over-compensation, and that this is the mechanism of the beneficial effect observed. These effects would not be observed in the animal bioassays since to show them it would be necessary to have at least three dose groups below the NOAEL. In addition, the strain of animal used would have to have a very low incidence of disease to show any effect. 

Mehendale HM. 1992. Biochemical mechanisms of biphasic dose-response relationships Role of hormesis. In Calabrese EJ, ed. Biological effects of low level exposures to chemicals and radiation. Workshop, Amherst, MA, April 30 - May 1, 1991. Chelsea, Ml Lewis Publishers, Inc., 59-94. 

In the case of a nutrient there is a low-dose adverse effect due to nutritional inadequacy, but the nature of the adverse effect is completely different from that which becomes manifest as the region of high-dose toxicity is entered. Also, the very large risk associated with severe nutrient deficiency at doses near zero is not at all present in the case of hormesis. 

Finally, the concept of hormesis (Section 4.12), threshold of toxicological concern (Section 4.13), and probabilistic methods for effect assessment (Section 4.14) will be briefly addressed. 

Hormesis is the term used for the phenomenon of stimulatory effects at low-level exposure, and inhibition at high-level exposure. The term derives from the Greek word Hormo which means excite or set in motion, and which is also the root of the word hormone. The concept of hormesis dates back to the 1920s. A substance showing hormesis has the opposite effect in small doses compared to effects at large doses. The definition of hormesis does not imply that low-dose effects are necessarily beneficial, only that they are opposite to high-dose effects. 

Such effects may be confused or obscured by normal biological variation, as they are typically only 30% to 60% above the control. Furthermore, if the background level of tumor incidence (or other effect being measured) is low, it may be impossible to assess hormesis. 

Even if hormesis occurs, there could still be a threshold for a toxic or adverse effect, below which positive effects may occur. Therefore, the significance in toxicological risk assessment and even in toxicology is not entirely clear (12). 

Hormesis the concept that at low doses of a toxicant there may be positive, beneficial effects, whereas at higher doses there will be toxic effects. 

Hormesis is the phenomenon whereby low doses of chemicals have positive, beneficial effects whereas higher doses are harmful. 

Figure 11.4 Nonconventional dose-response relationship involving low-dose effects and compensation. (I) True initiation of the response followed by a compensatory response that returns the effects to the 0% level. (II) A negative response due to overcompensation (hormesis) followed by recovery to the 0% effect level. (Ill) The standard sigmoidal dose-response relationship.

There is a class of curvilinear dose-response relationships in toxicological and epidemiological studies that may be described as U-shaped or J-shaped curves. Other terms such as biphasic, and more recently hormesis, have been used to refer to paradoxical effects of low-level toxicants. In brief, these dose-response curves reflect an apparent improvement or reversal in the effect of an otherwise toxic agent. These... 

A theory that has been gaining acceptance recently is that many chemicals have beneficial effects at very low doses and may perhaps stimulate protective mechanisms, and that as the dose increases the effects become adverse. This is known as hormesis and may occur as a result of more than one exposure to a chemical (see box). ... 

See also Benchmark Dose Exposure Assessment Exposure Criteria Hazard Identification Hormesis, LD50/ LC50 (Lethai Dosage 50/Lethai Concentration 50) Levels of Effect in Toxicoiogicai Assessment Maximum Allowable Concentration (MAC) Maximum Tolerated Dose (MTD) Pharmacokinetics/Toxicokinetics Reference Concentration (RfC) Reference Dose (RfD) Risk Assessment, Ecological Risk Assessment, Human Health Risk Characterization Toxicity, Acute. 

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