Ad hoc and Fast Forward: The Science of Hormesis Growth and Development

Abstract

BackgroundHormesis is a binary response phenomenon with low-dose stimulation (or inhibition) of effects by substances producing opposite high-dose responses. Hormesis, after decades of obscurity, has undergone a renaissance in recent years, with rapid growth benefiting greatly from the systematized efforts of such proponents as the hormesis group at the University of Massachusetts-Amherst led by Edward J. Calabrese.ObjectiveIn this commentary I analyze chemical hormesis methodology with reference to ad hoc scientific approaches for defining and characterizing hormesis.DiscussionsProponents of hormesis have attempted a scientific characterization of hormesis through a battery of ad hoc methodologies using unvalidated criteria and other mechanisms for persistent database searches rather than through de novo hypothesis testing specific for hormesis. Here I discuss various scientific problems with this search-over-experiment approach, as well as other aspects of attempts at defining and characterizing the field.ConclusionsWide acceptance of hormesis by the broad scientific community and adoption of hormesis by public agencies for inclusion in health and regulatory policies have not occurred. Reasons may include the singular nature of hormesis research and directions followed in hormesis methodologies.

Defining Hormesis: Evaluation of a Complex Concentration Response Phenomenon

“…Specific criticism was leveled at the inclusion criteria used for dose-response analysis and for determination of statistical significance of analyzed data. 6,21,39,40 Despite such criticisms, these studies provide a potentially useful framework of quantitative features associated with hormetic responses.…”

Bisphenol A and Risk Management Ethics

“…71 Others argue that low dose exposures to some chemicals sometimes have beneficial effects on human health by inducing adaptive responses, but this hypothesis is controversial. 72,73,74,75 …”

Inference for the existence of hormetic dose–response relationships in toxicology studies

“…Later, additional studies evaluated hormetic effects in toxicant dose-response (Calabrese and Baldwin, 2003;Calabrese and Cook, 2005). Although these studies highlighted the potential importance of hormesis, other authors have expressed skepticism, pointing out a lack of formality in the hypothesis testing procedures, unknown specificity and sensitivity, and potential adverse consequences of incorporating hormetic models into policy decisions (Crump, 2001;Thayer and others, 2005;Mushak, 2009). When attempting to distinguish hormesis from a monotonic dose-response relationship (see Figure 1), the importance of flexible dose-response modeling has been discussed (Sielken and Stevenson, 1998), and several dose-response models for testing monotonicity versus non-monotonicity have been proposed (Bowman and others, 1998;Hall and Heckman, 2000;Schabenberger and Birch, 2001;Hunt and Bowman, 2004;Hans and Dunson, 2005;Hunt and Rai, 2005;Belz and Piepho, 2012;Zhang and others, 2013;Kim and others, 2015).…”