Hormesis: The Dose-Response Revolution

Abstract

Hormesis, a dose-response relationship phenomenon characterized by low-dose stimulation and high-dose inhibition, has been frequently observed in properly designed studies and is broadly generalizable as being independent of chemical/physical agent, biological model, and endpoint measured. This under-recognized and -appreciated concept has the potential to profoundly change toxicology and its related disciplines with respect to study design, animal model selection, endpoint selection, risk assessment methods, and numerous other aspects, including chemotherapeutics. This article indicates that as a result of hormesis, fundamental changes in the concept and conduct of toxicology and risk assessment should be made, including (a) the definition of toxicology, (b) the process of hazard (e.g., including study design, selection of biological model, dose number and distribution, endpoint measured, and temporal sequence) and risk assessment [e.g., concept of NOAEL (no observed adverse effect level), low dose modeling, recognition of beneficial as well as harmful responses] for all agents, and (c) the harmonization of cancer and noncancer risk assessment.

Nutritional hormesis

“…The hormetic chemotherapeutic agents studied included antibacterial, antiviral, antitumor and antiangiogenesis agents, with their quantitative and temporal dose responses being similar to that reported for both chemicals and radiation (Calabrese and Baldwin, 2003b). Hormetic-like biphasic dose-responses have been reported in over 130 human tumor cell lines from a wide range of agents, including antineoplastics, toxic substances (i.e., environmental pollutants), non-neoplastic drugs, endogenous agonists and phyto-compounds (Calabrese, 2005b (Calabrese and Blain, 2004).…”

“…The synthetic plant growth inhibitor phosfon (2,4-dichlorobenzyl tributyl phosphonium chloride) exhibits a hormetic inverted U-shaped dose-response relationship on the growth of peppermint, Mentha piperita (Calabrese, 1999;Calabrese and Baldwin, 2003b;Kaiser, 2003). Growth stimulation occurred at lower phosfon doses with diminution of the stimulatory response at higher doses, leading to marked inhibitory growth depending on the specific range of doses employed.…”

Nontarget Insects Captured in Fruit Fly (Diptera: Tephritidae) Surveillance Traps

“…As seen in Figures 1 and 2, the adult males showed a typical hormetic response to the two alcohols, i.e., a nonlinear biphasic doseresponse relationship characterized by small quantities having opposite effects from large quantities (Calabrese and Baldwin 2003). For ethanol, the preference indices increased gradually with concentration from an approximate threshold of 0.25% (-2 in log scale; hereafter the log-scale concentration will be shown in parentheses after the percentage) to maximum responses at 2% (1) or 4% (2), after which they abruptly decreased toward repulsion; the highest repulsion was shown at the concentration of 64% (6) or 0.25% (-2).…”

Setting Ambient Water Quality Standards: New York State's Nonlinear Approach for Carcinogens

“…In other words, the critical effects decrease as dose decreases across all doses above zero (linear) or decrease as doses decreases across all doses above the threshold (nonlinear). 1\iYSDEC and NYSDOH staff are not at this time planning on further harmonization of the two approaches using recommendations suggested by Calabrese and Baldwin (2003), which incorporate hormesis into risk assessment. However, staff will continue to monitor the developments in the field of honnesis so as to fully understand the implications hormesis mayor will have in regulatory risk assessment.…”