Data quality and relevance in ecotoxicity: The undocumented influences of model assumptions and modifying factors on aquatic toxicity dose metrics

A model-based approach using hypothetical organic chemicals examines how aquatic toxicity test results are influenced by toxicity modifying factors such as hydrophobicity, exposure duration, body size, lipid content, mode of toxic action (via Critical Body Residue differences), and metabolic degradation. Differences of up to one to three orders of magnitude were identified for modeled LC50s. Dominance of CBR by low log Kow chemicals can cause further influences. Such differences cause significant changes in the relationship between exposure- and organism-based doses and create substantial difficulties for both interpretation of test results and extrapolation to other laboratory or field exposure conditions. The resulting variability is not readily evident in toxicity testing as insufficient data are collected to validate fundamental assumptions. Consequently, results obtained with standard aquatic toxicity test protocols do not yield consistent, comparable measures of relative toxicity and are inappropriate for quantitative toxicology and risk applications. The substantial uncertainties in testing results created by such undocumented variability must also be given serious consideration in data quality and relevance assessments. Necessary improvements in aquatic toxicity testing methodology should include explicit estimation of toxicokinetics and toxicodynamics and routine validation of toxicological model assumptions.