title: Fundamental flaws of hormesis for public health decisions.
abstract: Hormesis (defined operationally as low-dose stimulation, high-dose inhibition) is often used to promote the notion that while high-level exposures to toxic chemicals could be detrimental to human health, low-level exposures would be beneficial. Some proponents claim hormesis is an adaptive, generalizable phenomenon and argue that the default assumption for risk assessments should be that toxic chemicals induce stimulatory (i.e., "beneficial") effects at low exposures. In many cases, nonmonotonic dose-response curves are called hormetic responses even in the absence of any mechanistic characterization of that response. Use of the term "hormesis," with its associated descriptors, distracts from the broader and more important questions regarding the frequency and interpretation of nonmonotonic dose responses in biological systems. A better understanding of the biological basis and consequences of nonmonotonic dose-response curves is warranted for evaluating human health risks. The assumption that hormesis is generally adaptive is an oversimplification of complex biological processes. Even if certain low-dose effects were sometimes considered beneficial, this should not influence regulatory decisions to allow increased environmental exposures to toxic and carcinogenic agents, given factors such as interindividual differences in susceptibility and multiplicity in exposures. In this commentary we evaluate the hormesis hypothesis and potential adverse consequences of incorporating low-dose beneficial effects into public health decisions. Key words: biphasic dose response, hormesis, individual susceptibility, low-dose exposures, nonmonotonic dose response, nonlinear dose response, public health, regulation, risk assessment.
authors.affiliation: National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA. thayer@niehs.nih.gov
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Thayer
authors.forename: Ronald
authors.initials: R
authors.lastname: Melnick
authors.forename: Kathy
authors.initials: K
authors.lastname: Burns
authors.forename: Devra
authors.initials: D
authors.lastname: Davis
authors.forename: James
authors.initials: J
authors.lastname: Huff
mesh_terms: D003659:Decision Making, Organizational; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D006304:Health Status; D006801:Humans; D016273:Occupational Exposure; D011634:Public Health