User Guide to Thresholds and Classification - Environmental ...

376User Guide for Thresholds and Classificationsand bases, metals complexes, surface-active materials, or substances that react with the eluent. The HPLCmethod is applicable when the log KOW value falls within the range 0 to 6 (OECD 117, 1989). The HPLCmethod is less sensitive to the presence of impurities in the test compound compared to the shake-flaskmethod.Slow stirring methodWith the slow-stirring method provides a precise and accurate determination of KOW of compounds with logK OW up to 8.2 (De Bruijn et al, 1989). For highly lipophilic compounds the shake-flask method is prone toproduce artefacts (formation of micro-droplets), and with the HPLC method KOW needs to be extrapolatedbeyond the calibration range to obtain estimates of KOW. In order to determine a partition coefficient, water,n-octanol, and test compound are equilibrated with each other after which the concentration of the testcompound in the two phases is determined. The experimental difficulties associated with the formation ofmicro-droplets during the shake-flask experiment can to some degree be overcome in the slow-stirringexperiment as water, n-octanol, and the test compound are equilibrated in a gently stirred reactor. Thestirring creates a more or less laminar flow between the n-octanol and the water, and exchange between thephases is enhanced without micro-droplets being formed.Generator column methodAnother very versatile method for measuring log KOW is the generator column method. In this method, agenerator column method is used to partition the test substance between the n-octanol and water phases.The column is packed with a solid support and is saturated with a fixed concentration of the test substance inn-octanol. The test substance is eluted from the n-octanol -saturated generator column with water. Theaqueous solution exiting the column represents the equilibrium concentration of the test substance that haspartitioned from the octanol phase into the water phase. The primary advantage of the generator columnmethod over the shake flask method is that the former completely avoids the formation of micro-emulsions.Therefore, this method is particularly useful for measuring K OW for substances values over 4.5 (Doucette andAndren, 1987; 1988; Shiu et al, 1988) as well as for substances having log K OW < 4.5. A disadvantage of thegenerator column method is that it requires sophisticated equipment.Use of QSARs for determination of log K OW(See also section 19D.5 in Appendix 19D.)Numerous QSARs have been and continue to be developed for the estimation of K OW . Commonly usedmethods are based on fragment constants. The fragmental approaches are based on a simple addition ofthe lipophilicity of the individual molecular fragments of a given molecule. Three commercially available PCprograms are recommended in the European Commission‘s technical guidance document (EC, 1996) for riskassessment, part III, if no experimentally derived data are available.CLOGP (Daylight Chemical Information Systems, 1995) was initially developed for use in drug design. Themodel is based on the Hansch and Leo calculation procedure (Hansch and Leo, 1979). The programcalculates log K OW for organic compounds containing C, H, N, O, Hal, P, and/or S. Log K OW for salts and forJanuary 2012 EPA0109