Uncertainties associated with assessing the risk of an endocrine active substance in the Canadian environment

A number of biological responses and multigenerational effects, mediated th rough the disruption of endocrine systems, have been observed in biota expo sed to relatively low concentrations of environmental contaminants. These t ypes of responses need to be considered within a weight of evidence approac h in our risk assessment and risk management frameworks. However including endocrine responses in an environmental risk assessment introduces a number of uncertainties that must be considered. A risk assessment of nonylphenol and nonylphenol polyethoxylates (NP/NPE) is used as a case study to demons trate the sources and magnitude of some of the uncertainties associated wit h using endocrine disruption as an assessment endpoint. Even with this rela tively well studied group of substances, there are substantial knowledge ga ps which contribute to the overall uncertainties, limiting the interpretati on within the risk assessment. The uncertainty of extrapolating from in vit ro or biochemical responses to higher levels of organization or across spec ies is not well understood. The endocrine system is very complex and chemic als can interact or interfere with the normal function of endocrine systems in a number of ways (e.g., receptors, hormones) which may or may not resul t in an adverse! responses in the whole organism. Using endocrine responses can lead to different conclusions than traditional endpoints due to a vari ety of factors, such as differences in relative potencies of chemicals for specific endpoints (e.g., receptor binding versus chronic toxicity). The un certainties can also be considerably larger and the desirability of using e ndocrine endpoints should be carefully evaluated. Endocrine disruption is a mode of action and not a functional endpoint and this needs to be consider ed carefully in the problem formulation stage and the interpretation of the weight of evidence.