The concept of hormesis in developmental toxicology

Animal bioassay experiments are frequently conducted to assess the toxicity of chemicals on the developing fetus. Experiments are normally conducted a t dosage levels that are much higher than human exposure levels to elicit t he toxic reproductive effect of the chemical in a limited number of litters . Recently there has been much discussion on the fact that some chemicals m ay have beneficial effects at low doses and become toxic at high doses. Thi s concept, known as chemical hormesis, has been the focus of attention in m any investigations. Here, we consider the prevalence of hormesis in develop mental toxicology and show that current design of developmental toxicity te sting does not accommodate the study of hormesis. If it can be proved that some developmental toxicants may have stimulatory low dose effects, then de sign and analysis of developmental toxicity experiments need to be revised by the scientific community and the regulatory agencies. Using a thorough a nalysis of an experimental data set, we further demonstrate that in order t o establish the possible hormetic effects of a chemical in reproduction, of ten a multiple replication of the experiment may be necessary to examine su ch effects. Using a trend test, we illustrate that while it is:possible tha t one replicate of a developmental toxicity experiment with a known teratog en shows strong evidence of hormesis, other replicates may show no sign of beneficial effects at low doses.