U-Shaped Dose-Responses in Biology, Toxicology, and Public Health

Abstract

The occurrence of U-shaped dose-response relationships (often termed hormesis) has been documented in numerous biological, toxicological, and pharmacological investigations. Many of the endpoints studied are of considerable significance to public health (e.g. body weight, cholesterol levels, ethanol consumption, longevity, cancer incidence, etc). Despite the fact that U-shaped dose-responses are widely and independently observed, little attempt has been made to assess this phenomenon in an integrative manner. This review provides an overview of the historical foundations of hormesis and a discussion of its definition within a mechanistic framework. The occurrence, generalizability, and biological significance of U-shaped dose-response relationships along with the concept of biological optimality are addressed.

Transcriptional regulation of selenium-dependent glutathione peroxidase from Venerupis philippinarum in response to pathogen and contaminants challenge

“…Therefore, it was deduced that excess accumulation of Cu and Cd beyond a certain level in V. philippinarum could cause strong oxidative stress that dramatically lowered the metabolic capacity, which resulting in a decrease of antioxidant enzyme mRNA expression. This was in line with the hormesis phenomenon in toxicology, characterized by a low dose of stimulation and high dose of inhibition [37].…”

The effects of prenatal PCBs on adult female paced mating reproductive behaviors in rats

“…Overall, we observed the greatest number of effects of the intermediate(1 mg/kg) dosage of A1221, exposure to which affected adult mating trial pacing, receptivity/proximity behaviors, and audible vocalizations compared to control and lower or higher doses of A1221. This suggests the possibility of a non-linear dose response curve common to endocrine disruption studies (Calabrese and Baldwin, 2001; reviewed in Gore et al, 2006), wherein an intermediate dose level elicits the greatest effects. Thus, the paced mating paradigm reveals that small, ecologically relevant exposures at a precise developmental stage can permanently alter specific aspects of adult female-typical sexual behaviors.…”

Developmental toxicity of a commercial herbicide mixture in mice: I. Effects on embryo implantation and litter size.

“…This pattern has also been observed in immune suppression responses to the carbamate aldicarb (Olson et al 1987). The inverted or U-shaped doseresponse model, also known as hormesis, has been reviewed by Calabrese andBaldwin (1999, 2001). The model has been used to describe observations in a wide range of organisms (including bacteria and humans) and chemicals ranging from relatively safe agents to highly toxic compounds (e.g., see Figure 2 in Calabrese and Baldwin 1999).…”

“…The inverted or U-shaped doseresponse model, also known as hormesis, has been reviewed by Calabrese andBaldwin (1999, 2001). The model has been used to describe observations in a wide range of organisms (including bacteria and humans) and chemicals ranging from relatively safe agents to highly toxic compounds (e.g., see Figure 2 in Calabrese and Baldwin 1999). Wilson (1973) stated that "manifestations of deviant development increase in frequency and degree as dosage increases from the noeffect to the totally lethal level" (p. 30), indicating that the expected-and perhaps obvious-dose-litter-size relationship should have been linear.…”

“…Wilson (1973) stated that "manifestations of deviant development increase in frequency and degree as dosage increases from the noeffect to the totally lethal level" (p. 30), indicating that the expected-and perhaps obvious-dose-litter-size relationship should have been linear. Hormesis, as defined by Calabrese and Baldwin (2001), is an adaptive response to low levels of stress or damage resulting in improved fitness for some physiologic systems for a finite period. If our observation had been a true hormetic response, we would have observed an increase in litter size at the lower doses and not a decrease.…”