High Log Kow Research Articles

A Novel Method for Measuring Membrane-Water Partition Coefficients of Hydrophobic Organic Chemicals: Comparison with 1-Octanol–Water Partitioning

A novel method of measuring membrane-water partitioning characteristics of very hydrophobic organic chemicals is described. Partition coefficients are reported for a series of halogenated aromatic hydrocarbons of varying molar volume between water and L-a-phosphatidylcholine dimyristoyl (DMPC) membrane vesicles and two solvents, n-hexane and 1-octanol. The results indicate that n-hexane and 1-octanol are satisfactory surrogates for DMPC membranes for chemicals with 1-octanot-water partition coefficients (log KOW) < 5.5 or molar volumes < 230 cm3/mol. Chemicals with higher log KOW or molar volume values display marked differences in membrane-water, 1-octanol-water, and n-hexane-water partitioning. Implications for lipid- and organism-water partitioning of hydrophobic chemicals are discussed.

The use of quantitative structure‐activity relationships to predict the acute and chronic toxicities of organic chemicals to fish

AbstractQuantitative structure‐activity relationships (QSARs) predict bioconcentration and acute toxicity to fish of chemicals causing narcosis on the basis of hydrophobicity, as measured by the octanol/water partition coefficient (Kow). Since the development of water quality objectives to protect fish is limited by the availability of suitable chronic toxicity data, we applied the QSAR concept to published and unpublished data to determine (a) whether chronic toxicity could be related to Kow and (b) whether application factors are constant, i.e., whether QSARs for acute and chronic toxicity are parallel. Our conclusions are as follows: (1) A QSAR, based on hydrophobicity (log Kow), appears to exist for the chronic toxicity of organic chemicals inducing acute toxicity by narcosis. Although not definitive, this QSAR was not parallel to that for acute toxicity and does not appear to support the concept of constant application factors. (2) Log Kow has a major effect on the rate of net bioconcentration of certain organic chemicals; therefore, the relationship of toxicity to log Kow may not be linear if exposure times are fixed, as very different amounts of toxicants will be taken up over a fixed time period. (3) As a result of the effect of log Kow on bioconcentration rates, many toxicity tests of relatively short, fixed duration may underestimate toxicity of some hydrophobic organic compounds, especially those exhibiting high log Kow values. Hence, water quality objectives developed directly from this data, without appropriate compensation, may not be restrictive enough. (4) To increase the accuracy, comparability and applicability of aquatic bioassay test results, especially for compounds of widely differing hydrophobicity, standard tests should be redesigned. For example, it may be more accurate if the exposure or dosage for the test organism is expressed as a summation of the periodically calculated product of body toxicant level and time up to predetermined summation values.

THE USE OF QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS TO PREDICT THE ACUTE AND CHRONIC TOXICITIES OF ORGANIC CHEMICALS TO FISH

Quantitative structure-activity relationships (QSARs) predict bioconcentration and acute toxicity to fish of chemicals causing narcosis on the basis of hydrophobicity, as measured by the octanol/water partition coefficient (Kow). Since the development of water quality objectives to protect fish is limited by the availability of suitable chronic toxicity data, we applied the QSAR concept to published and unpublished data to determine (a) whether chronic toxicity could be related to Kow and (b) whether application factors are constant, i.e., whether QSARs for acute and chronic toxicity are parallel. Our conclusions are as follows: (1) A QSAR, based on hydrophobicity (log Kow), appears to exist for the chronic toxicity of organic chemicals inducing acute toxicity by narcosis. Although not definitive, this QSAR was not parallel to that for acute toxicity and does not appear to support the concept of constant application factors. (2) Log Kow has a major effect on the rate of net bioconcentration of certain organic chemicals; therefore, the relationship of toxicity to log Kow may not be linear if exposure times are fixed, as very different amounts of toxicants will be taken up over a fixed time period. (3) As a result of the effect of log Kow on bioconcentration rates, many toxicity tests of relatively short, fixed duration may underestimate toxicity of some hydrophobic organic compounds, especially those exhibiting high log Kow values. Hence, water quality objectives developed directly from this data, without appropriate compensation, may not be restrictive enough. (4) To increase the accuracy, comparability and applicability of aquatic bioassay test results, especially for compounds of widely differing hydrophobicity, standard tests should be redesigned. For example, it may be more accurate if the exposure or dosage for the test organism is expressed as a summation of the periodically calculated product of body toxicant level and time up to predetermined summation values.