Ecotoxicology dilemmas: issues with dose, causality, response, mixtures, and modifying factors

Ecotoxicology has model assumptions that are the basis of the discipline's scientific validity and regulatory utility. Using testing data to advance knowledge and practical applications is contingent on assumption validation of underlying models, an uncommon practice. Fundamental components-dose, causality, response-are confounded, as test metrics are each accumulations of a multiplicity of factors. Consequently, ecotoxicology test interpretation of both legacy and new approach methodologies is plagued by unaddressed issues related to interactions of within and between dose, causation, response, and modifying factors-each component is effectively a mixture-such that established relationships are more correlative than causal. Limited knowledge about the multiplicity of modifying factors influencing dose, causality, and response at each level of biological organization and the challenge of establishing dose metrics in upper ecological levels, where the paradigm is stressor-causality-response, further confounds the formidable task of in vitro to in vivo, laboratory-to-field, and toxicity-to-ecology translation. Although available aquatic ecotoxicity data and information have been successfully fitted to explanatory frameworks in past and present regulatory policies, environmental protection successes are more attributable to good policy than to scientific knowledge. Unresolved issues in the simple model frameworks and regulatory policies that initially advanced environmental protection are now impeding development of newer policies and procedures due to inadequate consideration of basic model assumptions. Resolution of the problem will begin when the problem definition of the tasks is refined to reflect the reality of the challenge. This is a necessary step towards achieving the objective of advancing the efficiency, effectiveness, and sophistication of environmental effects assessment and management in regulatory ecotoxicology.