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334User Guide for Thresholds and ClassificationsThus, to compare these data to each other and to the criteria, some common basis or normalisation will berequired. It has been noted that there is a close relationship between the lipid content of a fish or an aquaticorganism and the observed BCF value. Therefore, when comparing BCF values across different fish speciesor when converting BCF values for specific organs to whole body BCFs, the common approach is to expressthe BCF values on a common lipid content. If, for example, whole body BCF values or BCF values forspecific organs are found in the literature, the first step is to calculate the BCF on a percentage lipid basisusing the relative content of fat in the fish (compare with the literature/test guideline for typical fat content ofthe test species) or the organ. In the second step the BCF for the whole body for a typical aquatic organism(that is, small fish) is calculated assuming a common default lipid content. A default value of 5% is mostcommonly used (Pedersen et al, 1995) as this represents the average lipid content of the small fish used inOECD 305 (1996).Generally, the highest valid BCF value expressed on this common lipid basis is used to determine the wetweight based BCF-value in relation to the cut off value for the BCF of 500 of the HSNO Act classificationcriteria.Use of radiolabelled substancesThe use of radiolabelled test substances can facilitate the analysis of water and fish samples. However,unless combined with a specific analytical method, the total radioactivity measurements potentially reflect thepresence of the parent substance as well as possible metabolite(s) and possible metabolised carbon, whichhave been incorporated in the fish tissue in organic molecules. BCF values determined by use ofradiolabelled test substances are therefore normally overestimated.When using radiolabelled substances, the labelling is most often placed in the stable part of the molecule, forwhich reason the measured BCF value includes the BCF of the metabolites. For some substances it is themetabolite which is the most toxic and which has the highest bioconcentration potential. Measurements ofthe parent substance as well as the metabolites may thus be important for the interpretation of the aquatichazard (including the bioconcentration potential) of such substances.In experiments where radiolabelled substances have been used, high radiolabel concentrations are oftenfound in the gall bladder of fish. This is interpreted to be caused by biotransformation in the liver andsubsequently by excretion of metabolites in the gall bladder (Comotto et al, 1979; Goodrich et al, 1991;Toshima et al, 1992; Wakabayashi et al, 1987). When fish do not eat, the content of the gall bladder is notemptied into the gut, and high concentrations of metabolites may build up in the gall bladder. The feedingregime may thus have a pronounced effect on the measured BCF. In the literature many studies are foundwhere radiolabelled compounds are used, and where the fish are not fed. As a result high concentrations ofradioactive material are found in the gall bladder. In these studies the bioconcentration may in most caseshave been overestimated. Thus when evaluating experiments, in which radiolabelled compounds are used, itis essential to evaluate the feeding regime as well.If the BCF in terms of radiolabelled residues is documented to b-state, are for, forJanuary 2012 EPA0109
335User Guide for Thresholds and Classificationsexample, pesticides strongly recommended in the OECD Test Guideline 305 (1996). If no identification andquantification of metabolites are available, the assessment of bioconcentration should be based on themeasured radiolabelled BCF value.on the parent compound and on radiolabelled measurements are available, the latter should thus be used inrelation to classification.Octanol-water-partitioning coefficientFor organic substances experimentally derived high-quality KOW values, or values that are evaluated inreviews and assigned as the ‗recommended values‘, are preferred over other determinations of KOW. Whenno experimental data of high quality are available, validated QSARs for log KOW may be used in theclassification process. Such validated QSARs may be used without modification to the agreed criteria if theyare restricted to chemicals for which their applicability is well characterised. For substances like strong acidsand bases, substances that react with the eluent, or surface-active substances, a QSAR estimated value ofKOW or an estimate based on individual n-octanol and water solubilities should be provided instead of ananalytical determination of KOW (EEC A8; OECD 117). Measurements should be taken on ionisablesubstances in their non-ionised form (free acid or free base) only by using an appropriate buffer with pHbelow pK for free acid or above the pK for free base.Experimental determination of K OWFor experimental determination of K OW values, several different methods, Shake-flask, and HighPerformance Liquid Chromatography (HPLC), are described in standard guidelines, see Appendix 19A. Theshake-flask method is recommended when the log K OW value falls within the range from –2 to 4. The shakeflaskmethod applies only to essential pure substances soluble in water and n-octanol. For highly lipophilicsubstances, which slowly dissolve in water, data obtained by employing a slow-stirring method are generallymore reliable. Furthermore, the experimental difficulties, associated with the formation of microdropletsduring the shake-flask experiment, can to some degree be overcome by a slow-stirring method where water,octanol, and test compound are equilibrated in a gently stirred reactor. With the slow-stirring method (OECDTest Guideline 123) a precise and accurate determination of K OW of compounds with log K OW of up to 8.2 isallowed. As for the shake-flask method, the slow-stirring method applies only to essentially pure substancessoluble in water and n-octanol. The HPLC method, which is performed on analytical columns, isrecommended when the log K OW value falls within the range 0 to 6. The HPLC method is less sensitive to thepresence of impurities in the test compound compared to the shake-flask method. Another technique formeasuring log K OW is the generator column method (USEPA, 1996b). As an experimental determination ofthe K OW is not always possible, for example, for very water soluble substances, very lipophilic substances,and surfactants, a QSAR-derived K OW may be used.Use of Quantitative Structure Activity Relationships for determination of log K OWWhen an estimated K OW value is found, the estimation method has to be taken into account. NumerousQSARs have been and continue to be developed for the estimation of K OW . Four commercially availablecomputer programs (CLOGP, LOGKOW (KOWWIN), AUTOLOGP, and SPARC) are frequently used for riskJanuary 2012 EPA0109
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