Hormesis is central to toxicology, pharmacology and risk assessment

2010 ◽  
Vol 29 (4) ◽  
pp. 249-261 ◽  
Author(s):  
Edward J Calabrese
Keyword(s):  
Risk Assessment ◽  
Dose Response ◽  
Low Dose ◽  
Assessment Practices ◽  
Biological Organization ◽  
Setting Process ◽  
Toxicological Research ◽  
Multiple Levels ◽  
Dose Responses ◽  
Chemical Class

This paper summarizes numerous conceptual and experimental advances over the past two decades in the study of hormesis. Hormesis is now generally accepted as a real and reproducible biological phenomenon, being highly generalized and independent of biological model, endpoint measured and chemical class/physical stressor. The quantitative features of the hormetic dose response are generally highly consistent, regardless of the model and mechanism, and represent a quantitative index of biological plasticity at multiple levels of biological organization. The hormetic dose-response model has been demonstrated to make far more accurate predictions of responses in low dose zones than either the threshold or linear at low dose models. Numerous therapeutic agents widely used by humans are based on the hormetic dose response and its low dose stimulatory characteristics. It is expected that as low dose responses come to dominate toxicological research that risk assessment practices will incorporate hormetic concepts in the standard setting process.

scholarly journals Hormesis: Implications for Cancer Risk Assessment

Dose-Response ◽  
2005 ◽  
Vol 3 (3) ◽  
pp. dose-response.0 ◽  
Author(s):  
Jonathan Borak ◽  
Greg Sirianni
Keyword(s):  
Risk Assessment ◽  
Cancer Risk ◽  
Dose Response ◽  
Low Dose ◽  
Cancer Risk Assessment ◽  
Response Curves ◽  
Response Characteristics ◽  
Non Linear ◽  
Dose Responses ◽  
Current Guidelines

Current guidelines for cancer risk assessment emphasize a toxicant's “mode of action”, rather than its empirically derived dose-response relationship, for determining whether linear low-dose extrapolation is appropriate. Thus, for reasons of policy, demonstration of hormesis is generally insufficient to justify a non-linear approach, although it may provide important insights into the actions of toxicants. We evaluated dose-response characteristics of four carcinogens reported to have hormetic dose-response curves: cadmium chloride; ionizing radiation; PAHs; and, 2,3,7,8-TCDD. For each, the study that documented hormesis in one organ also provided evidence of non-hormetic dose-responses in other organs or non-hormetic responses for seemingly similar carcinogens in the same species and organs. Such inconsistency suggests toxicologic reasons that the finding of hormesis alone is not sufficient to justify use of non-linear low-dose extrapolations. Moreover, available data in those examples are not sufficient to know whether hormesis is a property of the toxicants, the target organ, or the exposed species. From the perspectives of cancer risk assessment, the greatest informational value of hormesis may be that it provokes mechanistic studies intended to explain why hormesis occurs.

Another California Milestone: The First Application of Hormesis in Litigation and Regulation

2008 ◽  
Vol 27 (1) ◽  
pp. 31-33 ◽  
Author(s):  
Edward J. Calabrese
Keyword(s):  
Risk Assessment ◽  
Environmental Assessment ◽  
Assessment Practices ◽  
The Past ◽  
Research Communities ◽  
Toxicological Research

The concept of hormesis has been receiving greater interest in the biomedical and toxicological research communities over the past decade. Of particular importance has been how the hormesis concept may affect risk assessment practices, litigation, and regulation. This paper identifies and discusses what may be the first application of the hormesis concept in environmental assessment and litigation. This occurred in California within the context of an assessment of alleged continuing smelter contamination nearly a century ago.

scholarly journals Biphasic and triphasic dose responses in zebrafish embryos to low-dose 150 kV X-rays with different levels of hardness

2016 ◽  
Vol 57 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Eva Yi Kong ◽  
Shuk Han Cheng ◽  
Kwan Ngok Yu
Keyword(s):  
Dose Response ◽  
Low Dose ◽  
High Dose ◽  
X Rays ◽  
Acridine Orange Staining ◽  
Living Organisms ◽  
Dose Responses ◽  
Different Levels ◽  
Danio Rerio Embryos

Abstract The in vivo low-dose responses of zebrafish ( Danio rerio ) embryos to 150 kV X-rays with different levels of hardness were examined through the number of apoptotic events revealed at 24 h post fertilization by vital dye acridine orange staining. Our results suggested that a triphasic dose response was likely a common phenomenon in living organisms irradiated by X-rays, which comprised an ultra-low-dose inhibition, low-dose stimulation and high-dose inhibition. Our results also suggested that the hormetic zone (or the stimulation zone) was shifted towards lower doses with application of filters. The non-detection of a triphasic dose response in previous experiments could likely be attributed to the use of hard X-rays, which shifted the hormetic zone into an unmonitored ultra-low-dose region. In such cases where the subhormetic zone was missed, a biphasic dose response would be reported instead.

Hormesis, resveratrol and plant-derived polyphenols: some comments

2011 ◽  
Vol 30 (12) ◽  
pp. 2027-2030 ◽  
Author(s):  
Salvatore Chirumbolo
Keyword(s):  
Risk Assessment ◽  
Dose Response ◽  
Adaptive Response ◽  
Low Dose ◽  
High Dose ◽  
Low Doses ◽  
General Behaviour

Hormesis is a dose–response phenomenon, usually present in plants and animals, characterized by a low-dose stimulation and high-dose inhibition, often resulting in typical U-shaped or J-shaped curves. Hormesis has become an interesting model for toxicology and risk assessment, as it has been described for several nature-derived phytochemicals but also because this adaptive response to stressors might hide an underlying more general behaviour of cell towards low doses.

Scientific Trends in Risk Assessment Research

1989 ◽  
Vol 5 (5) ◽  
pp. 777-790 ◽  
Author(s):  
Elizabeth L. Anderson
Keyword(s):  
Public Health ◽  
Risk Assessment ◽  
Exposure Assessment ◽  
Dose Response ◽  
Low Dose ◽  
Scientific Data ◽  
Weight Of Evidence ◽  
Dose Effects ◽  
Recent Trends ◽  
Assessment Research

The use of risk assessment approaches to evaluate the effects of toxic chemicals had its primary origin in 1976 when the U. S. Environmental Protection Agency (EPA) adopted the first federal guidelines to commit a major regulatory agency to risk assessment approaches for the evaluation of suspect carcinogens. The accom panying policy statement also adopted a risk management policy, which acknowledged that the agency would accept risk in making public health policy decisions; in essence, this represented a pri mary departure from the zero-risk goal that had dominated the first half of the environmental movement of the '70s. The approach adopted in 1976 was based on the experience of risk assessment approaches used for assessing low-dose-radiation effects on human health. To be certain that no public health risk be underestimated, particularly in light of the prior zero-risk goal, the practice of risk assessment for the first decade relied heavily on extremely protec tive assumptions in all aspects of the assessment process. For example, these assumptions included ranking the weight-of- evidence according to results in all related studies without regard for distinctions of tumor end point relevance to humans and the possibility that low-dose effects at environmental exposures might not be the same as high-dose effects. For low-dose-response charac terization, the practice has been to characterize a plausible upper bound on risk by the use of a low-dose linear non-threshold dose- response curve. Exposure assessment likewise relied on maximum plausible assumptions to characterize exposure. More recently, more attention is being paid to developing accurate scientific data bases that advance almost every aspect of the risk assessment pro cess in the direction of more accurate risk characterization. This paper will discuss the recent trends in weight-of-evidence characterization, dose-response modeling, and exposure assessment and will compare the outcomes of these refined assessments to those evaluations that have relied on the earlier, conservative approaches. In essence, if the practices of the first decade for estab lishing plausible upper bounds on the risk were accurate, improved scientific data by and large should be expected to lower the overall theoretical risk. Indeed, this is the case when recent risk assessment research is applied but there are examples to the contrary. This paper represents a survey of recent trends and applications.

scholarly journals Toxic Responses Induced at High Doses May Affect Benchmark Doses

Dose-Response ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 155932582091960 ◽  
Author(s):  
Jürg A. Zarn ◽  
Ursina A. Zürcher ◽  
H. Christoph Geiser
Keyword(s):  
Dose Response ◽  
Low Dose ◽  
Dose Range ◽  
Reference Points ◽  
Benchmark Dose ◽  
High Dose ◽  
Low Doses ◽  
Confidence Bounds ◽  
Lower Confidence Bounds ◽  
Dose Responses

To derive reference points (RPs) for health-based guidance values, the benchmark dose (BMD) approach increasingly replaces the no-observed-adverse-effect level approach. In the BMD approach, the RP corresponds to the benchmark dose lower confidence bounds (BMDLs) of a mathematical dose–response model derived from responses of animals over the entire dose range applied. The use of the entire dose range is seen as an important advantage of the BMD approach. This assumes that responses over the entire dose range are relevant for modeling low-dose responses, the basis for the RP. However, if part of the high-dose response was unnoticed triggered by a mechanism of action (MOA) that does not work at low doses, the high-dose response distorts the modeling of low-dose responses. Hence, we investigated the effect of high-dose specific responses on BMDLs by assuming a low- and a high-dose MOA. The BMDLs resulting from modeling fictitious quantal data were scattered over a broad dose range overlapping with the toxic range. Hence, BMDLs are sensitive to high-dose responses even though they might be irrelevant to low-dose response modeling. When applying the BMD approach, care should be taken that high-dose specific responses do not unduly affect the BMDL that derives from low doses.

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