| Hormesis and Its Place in Nonmonotonic Dose–Response Relationships: Some Scientific Reality Checks Paul Mushak PB Associates, Durham, North Carolina, USA Abstract
Objective: This analysis is a critical assessment of current hormesis literature. I discuss definitions, characterization, generalizability, mechanisms, absence of empirical data specific for hormesis hypothesis testing, and arguments that hormesis be the "default assumption" in risk assessment. Data sources: Hormesis, a biological phenomenon typically described as low-dose stimulation from substances producing higher-dose inhibition, has recently garnered interest in several quarters. The principal sources of published materials for this analysis are the writings of certain proponents of hormesis. Surprisingly few systematic critiques of current hormesis literature exist. Limits to the phenomenon's appropriate role in risk assessment and health policy have been published. Data synthesis: Serious gaps in scientific understanding remain: a stable definition ; generalizability, especially for humans ; a clear mechanistic basis ; limitations in the presence of multiple toxic end points, target organs, and mechanisms. Absence of both arms-length, consensus-driven, scientific evaluations and empirical data from studies specifically designed for hormesis testing have limited its acceptance. Conclusions: Definition, characterization, occurrence, and mechanistic rationale for hormesis will remain speculative, absent rigorous studies done specifically for hormesis testing. Any role for hormesis in current risk assessment and regulatory policies for toxics remains to be determined. Key words: bidirectional dose response, biphasic dose response, hormesis, nonmonotonic dose response. Environ Health Perspect 115:500–506 (2007) . doi:10.1289/ehp.9619 available via http://dx.doi.org/ [Online 4 January 2007]
Address correspondence to P. Mushak, PB Associates, 714 9th St., Ste. 204, Durham, NC 27705-4849 USA. Telephone: (919) 286-7193. Fax: (919) 286-7369. E-mail: pandbmushak@cs.com I thank J.M. Davis for a number of discussions and B. Mushak for editing assistance. The author declares he has no competing financial interests. Received 16 August 2006 ; accepted 4 January 2007.
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