Human and Experimental Toxicology

Dayan, A D ;Hayes, A Wallace

doi: 10.1177/096032719801700501pmid: N/A

doi: 10.1177/096032719801700502pmid: N/A

doi: 10.1177/096032719801700503pmid: N/A

Calabrese, Edward J.

doi: 10.1177/096032719801700504pmid: N/A

Bailer, A John ;Oris, James T

doi: 10.1177/096032719801700505pmid: 9663930

The phenomenon of subtoxic stimulation of organism response is not uncommon in aquatic toxicology experiments. We describe the presence of hormesis in both growth and reproduction experiments in aquatic toxicology where these responses are observed in both animals and plants and at different trophic levels of an ecosystem. The implications of ignoring hormetic responses in the analysis of toxicity data are discussed. In particular, we note that specification of models that explicitly cannot accommodate or remove potential effects of hormesis may lead to biased potency estimates. Further, the presence of hormesis has implications for the design of toxicology experiments, with the spacing of concentration test conditions being critical.

Gaylor, David

doi: 10.1177/096032719801700506pmid: 9663931

Teeguarden, Justin G ;Dragan, Yvonne P ;Pitot, Henry C

doi: 10.1177/096032719801700507pmid: 9663932

Hormesis has been defined as a dose-response relationship which depicts improvement in some endpoint (increased metabolic rates, reduction in tumor incidence, etc.) at low doses of a toxic compound followed by a decline in the endpoint at higher doses. The existence of hormetic responses to carcinogenic agents has several implications for the bioassay and hazard assessment of carcinogens. To be capable of detecting and statistically testing for hormetic or other nonlinear dose-response functions, current study designs must be modified to include lower doses and sufficiently large numbers of animals. In addition, improved statistical methods for testing nonlinear dose-response relationships will have to be developed. Research integrating physiologically-based pharmacokinetic model descriptions of target dose with mechanistic data holds the greatest promise for improving the description of the dose-response curve at low doses. The 1996 Proposed Carcinogen Risk Assessment Guidelines encourage the use of mechanistic data to improve the descriptions of the dose-response curve at low doses, but do not distinguish between the types of nonlinear dose-response curves. Should this refined approach lead to substantial support for hormesis in carcinogenic processes, future guidelines will need to provide guidance on establishing safe doses and communicating the results to the public.

Jr, Robert L Sielken,;Stevenson, Donald E

doi: 10.1177/096032719801700508pmid: 9663933

The existence of hormesis should impact quantitative risk assessment in at least seven fundamental ways. (1) The dose-reponse models for bioassay and epidemiological data should have greater flexibility to fit the observed shape of the dose-response data and no longer be forced to always be linearly increasing at low doses. (2) Experimental designs should be altered to provide greater opportunity to identify the hormetic component of a dose-response relationship. (3) Rather than a lifetime average daily dose or its analog for shorter time periods, dose scales or metrics should be used that reflect the age or time dependence of the dose level. (4) Low-dose risk characterization should include the likelihood of bene-ficial effects and the likelihood that a dose level has reasonable certainty of no appreciable adverse health effects. (5) Exposure assessments should make greater efforts to characterize the distribution of actual doses from exposure rather than just upper bounds. (6) Uncertainty characterizations should be expanded to include both upper and lower bounds, and there should be an increased explicit use of expert judgement and weight-of-evidence based distributional analyses reflecting more of the available relevant dose-response information and alternative risk characterizations. (7) Risk should be characterized in terms of the net effect of a dose on health rather than a dose's effect on a single factor affecting health - for example, risk would be better expressed in terms of mortality from all causes combined rather than a specific type of fatal disease.

Johnson, Thomas E ;Bruunsgaard, Helle

doi: 10.1177/096032719801700509pmid: 9663934

Rather than being an exception, non-linearity between dose and response are the rule in biological systems. It might even be anticipated that at some doses a response opposite to that seen at high doses could be elicited (hormesis). Such non-linearity with dose has multiple implications for numerous aspects of biomedical research on aging and for experimental design. Moreover, the implications of such non-linearity are such that governmental regulatory activities and other areas of public health administration will be affected to a large extent once hormesis is widely recognized. The implications with regard to environmental intervention and subsequent regulatory decisions will certainly profoundly affect the political process, as well.

Morse, Joseph G

doi: 10.1177/096032719801700510pmid: 9663935

Resurgence of pest insects and mites and secondary pest outbreaks are commonly observed following pesticide applications on agricultural commodities. Reduction of natural enemy populations is the major factor blamed for these phenomena but insect or mite hormesis is a second, often overlooked factor which may be partially responsible. A major impact of hormesis is that it often leads to the need for additional pesticide treatments and can result in a spiralling increase in the use of pesticides, a term labelled in entomological literature as the `pesticide syndrome'.