User Guide to Thresholds and Classification - Environmental ...

340User Guide for Thresholds and ClassificationsWhether or not a substance has a potential for bioconcentration in aquatic organisms could thus be decidedin accordance with the following scheme.a. Valid/high quality experimentally determined BCF value = YES:ation.BCF < 500: The substance does not have a potential for bioconcentration.b. Valid/high quality experimentally determined BCF value = NO:Valid/high quality experimentally determined log KOW value = YES:Log K OWioconcentration.Log K OW < 4: The substance does not have a potential for bioconcentration.c. Valid/high quality experimentally determined BCF value = NO:Valid/high quality experimentally determined log K OW value = NO:Use of validated QSAR for estimating a log K OW value = YES:Log K OW ≥ 4: The substance has a potential for bioconcentrationLog K OW < 4: The substance does not have a potential for bioconcentration.19D.5 Use of Quantitative Structure Activity RelationshipsHistoryQSARs in aquatic toxicology can be traced to the work of Overton in Zürich (Lipnick, 1986) and Meyer inMarburg (Lipnick, 1989). They demonstrated that the potency of substances producing narcosis in tadpolesand small fish is in direct proportion to their partition coefficients measured between olive oil and water.Overton postulated in his 1901 monograph Studien über die Narkose that this correlation reflects toxicitytaking place at a standard molar concentration or molar volume within some molecular site within theorganism (Lipnick, 1991a). In addition, he concluded that this corresponds to the same concentration orvolume for a various organisms, regardless of whether uptake is from water or via gaseous inhalation. Thiscorrelation became known in anaesthesia as the Meyer-Overton theory.Corwin Hansch and co-workers at Pomona College proposed the use of n-octanol/water as a standardpartitioning system, and found that these partition coefficients were an additive, constitutive property that canbe directly estimated from chemical structure. In addition, they found that regression analysis could be usedto derive QSAR models, providing a statistical analysis of the findings. Using this approach, in 1972 theseworkers reported 137 QSAR models in the form log (1/C) = A log KOW + B, where KOW is the n-octanol/water partition coefficient, and C is the molar concentration of a chemical yielding a standardbiological response for the effect of simple non-electrolyte non-reactive organic compounds on wholeanimals, organs, cells, or even pure enzymes. Five of these equations, which relate to the toxicity of fivesimple monohydric alcohols to five species of fish, have almost identical slopes and intercepts and are in factvirtually the same as those found by Könemann in 1981, who appears to have been unaware of Hansch‘searlier work. Könemann and others have demonstrated that such simple non-reactive non-electrolytes all actJanuary 2012 EPA0109