Hormesis — does it have relevance at the population, community or ecosystem levels of organization?

In his paper entitled ‘‘The Impact of Hormesis to Ecotoxicology and Ecological Risk Assessment (ERA),’’ Peter Chapman has called for changes in the risk assessment paradigm to accommodate the concept of hormesis. As he points out in his paper, there are certain parallels between hormesis and some ‘‘low-dose effects’’ that have been described at the individual, population and ecosystem levels of organization. These low-dose effects and how to interpret them in risk assessment paradigms have become the fulcrum of a debate between those who think a shift in the standard toxicological paradigms of dose–response relationships and receptor-mediated responses is required and more traditional toxicologists who maintain that no such shift in paradigm is required. This is due, in part, to differences in opinion over whether increases in a response parameter near the no observable effect concentration (NOEC) are not adverse. One of the basic tenants on which traditional toxicology is built is the concept of the dose–response relationship. Furthermore, there is the concept of a threshold, below which no adverse effects would be observed. Thus, this is where the concept of hormesis potentially comes into play. The debate over safety of chemicals in the environment ranges from two extremes. They are those who believe that by their very nature they must cause adverse effects but that they may be subtle or are beyond the ability of modern science to measure. At the other end of the spectrum are those who believe that there are thresholds below which organisms can be exposed indefinitely to a stressor without adverse effect. More recently, the debate over the potential for adverse effects from low-dose exposures has been subsumed into the debate of environmental endocrine disruptors. Specifically, it has been suggested by some that there is, in fact, no threshold for endocrine-modulating effects. Furthermore, there has been discussion, particularly about compounds that might be weak hormone receptor agonists and thus mimic hormones, that there is a ‘‘less is more phenomenon’’ where exposure to lesser concentrations of a hormone mimic could result in a greater response than greater concentrations. Most of the compounds being discussed in the debate or weak estrogen receptor (ER) agonists, such as o,p-DDE, bisphenol-A and 4-nonylphenol. It has been suggested that these compounds can cause an inverted ‘‘U’’-type response. In fact, we have observed this phenomenon for fecundity of fathead minnows exposed to 4-nonylphenol. The primary issues are whether this phenomenon occurs through a receptormediated process and whether this phenomenon would affect the way risk assessments are currently conducted. The debate is, in my opinion, a misunderstanding. It seems that the misunderstanding stems from the assumption that low-level effects are mediated by the same mechanism as those observed at greater concentrations. It is further assumed that compounds that have been identified as weak hormone receptor agonists only cause effects through this mechanism of action, when in fact, there may be multiple mechanisms of action involved. For instance, the herbicide atrazine can cause estrogenic effects in vitro and in vivo, but does not bind to the ER. In the case of atrazine, it has been found that it can activate CYP19 (aromatase), the enzyme responsible for transforming testosterone into estradiol. In the case of 4-nonylphenol, it is likely that the lowlevel effects observed in fish are due to a mechanism other than that mediated through the ER. Hormesis has been observed in a wide range of responses in cells, tissues and individuals of a wide range of species. The issue is whether the concept and terminology are appropriate to be applied to other levels of organization, such as populations, communities or ecosystems. Hormetic responses *Correspondence: John P. Giesy, PhD, Department of Zoology, 203 Natural Science Building, Michigan State University, East Lansing, Michigan 48824, USA Human & Experimental Toxicology (2001) 20, 517–520 C 2001 Arnold All rights reserved 0960-3271/01