text: The pioneer work of identifying the major categories of modes of toxic action (see description above) was conducted by investigators from the U.S. Environmental Protection Agency (EPA) at the Duluth Laboratory using fish, reason why they named the categories as Fish Acute Toxicity Syndromes (FATS). They proposed the FATS by assessing the behavioral and physiological responses of the fish when subjected to toxicity tests, such as locomotive activities, body color, ventilation patterns, cough rate, heart rate, and others.
  It has been proposed that modes of toxic action could be estimated by developing a data set of critical body residues (CBR). The CBR is the whole-body concentration of a chemical that is associated with a given adverse biological response and it is estimated using a partition coefficient and a bioconcentration factor. The whole-body residues are reasonable first approximations of the amount of chemical present at the toxic action site(s). Because different modes of toxic action generally appear to be associated with different ranges of body residues, modes of toxic action can then be separated into categories. However, it is unlikely that every chemical has the same mode of toxic action in every organism, so this variability should be considered. The effects of mixture toxicity should be considered as well, even though mixture toxicity it's generally additive, chemicals with more than one mode of toxic action may contribute to toxicity.
  Modeling has become a common used tool to predict modes of toxic action in the last decade. The models are based in Quantitative Structure-Activity Relationships (QSARs), which are mathematical models that relate the biological activity of molecules to their chemical structures and corresponding chemical and physicochemical properties. QSARs can then predict modes of toxic action of unknown compounds by comparing its characteristic toxicity profile and chemical structure to reference compounds with known toxicity profiles and chemical structures. Russom and colleagues were one of the first group of researchers being able to classify modes of toxic action with the use of QSARs; they classified 600 chemicals as narcotics. Even though QSARs are a useful tool for predicting modes of toxic action, chemicals having multiple modes of toxic action can obscure QSAR analyses. Therefore, these models are continuously being developed.