The EPA Fathead Minnow Acute Toxicity database was generated by the U.S. EPA Mid-Continental Ecology Division (MED) for the purpose of developing an expert system to predict acute toxicity from chemical structure based on mode of action considerations. Hence, an important and unusual characteristic of this toxicity database is that the 617 tested industrial organic chemicals were expressly chosen to serve as a useful training set for development of predictive quantitative structure-activity relationships (QSARs). A second valuable aspect of this database, from a QSAR modeling perspective, is the inclusion of general mode-of-action (MOA) classifications of acute toxicity response for individual chemicals derived from study results. MOA assignments are biologically based classifications, allowing definition of chemical similarity based upon biological activity instead of organic chemistry functional class as most commonly employed in QSAR study. MOA classifications should strengthen the scientific basis for construction of individual QSARs. However, it is cautioned that the broad MOA categorizations should not be construed to represent a single molecular mechanism; for example, CNS seizure agents and respiratory inhibitors are known to act through a variety of receptors. The EPA Fathead Minnow database and results have been used by EPA MED to build components of the ASTER prediction system, which incorporates MOA-based QSARs for the prediction of aquatic toxicity of environmental and industrial chemicals. Briefly, MOA classifications for individual chemicals, derived from experiments and provided in the EPA Fathead Minnow database, were used to derive substructural rules for assigning a new chemical to an MOA category based solely on chemical structure. Once a new chemical is assigned to an MOA category on this basis, the logP-based QSAR for that MOA category is applied.

The DSSTox EPAFHM database (available from the DSSTox Source URL) includes information pertaining to organic chemical class assignments (ChemClass_FHM), acute toxicity in fathead minnow (LC50_mg), dose-response assessments (LC50_Ratio, ExcessToxicityIndex), behavioral assessments (FishBehaviorTest), joint toxicity MOA evaluations of mixtures (MOA_MixtureTest), and additional MOA evaluation of fish acute toxicity syndrome (FishAcuteToxSyndrome) in rainbow trout. All of these indicators, to the extent available, were considered in the determination of MOA and, additionally, were used to determine a level of confidence in the MOA assignment for each chemical (MOA_Confidence). Activity Outcome is based on reported LC50_mg: "active" = LC50_mg is reported; "inconclusive"= only partial mortality was reached at the highest tested dose; "inactive" = no mortality at the highest tested dose. Activity Score is mapping of LOG10 (1/LC50_mmol) activity values spanning activity range [MIN, MAX] onto Integer 1-100 Activity range, where 100 is highest potency and 1 is lowest. If Activity Outcome is "active": Activity Score = 100 * INTEGER[(log10(1/ LC50_mmol) - MIN)/(MAX # MIN)]. If Activity Outcome is "inactive" or "inconclusive": ActivityScore = 0.

DSSTox (EPAFHM): EPA Fathead Minnow Acute Toxicity

To access complete SD file and documentation, refer to the DSSTox EPAFHM Download Page

For more information and description pertaining to this assay, see EPA Fathead Minnow Database Information Page


Main Citation: Russom, C.L., S.P. Bradbury, S.J. Broderius, D.E. Hammermeister, and R.A. Drummond (1997) Predicting modes of action from chemical structure: Acute toxicity in the fathead minnow (Pimephales promelas). Environmental Toxicology and Chemistry, 16(5): 948-967.