Consolidated octanol/water partition coefficients: Combining multiple estimates from different methods to reduce uncertainties in log KOW

Background: The octanol/water partition coefficient ( K _OW ) is a key parameter for assessing the fate and effects of chemicals. It is a metric of their hydrophobicity, related to uptake and accumulation in organisms and specific tissues, and distribution in water, soil and sediments. The log K _OW can be determined experimentally, more often it is calculated. Variability may be due to properties of the substances, different experimental methods, or different computational approaches with different domains of applicability. The objective of the present study is to derive coherent log K _OW estimates with known variability by (1) estimating multiple log K _OW values by different methods for diverse chemicals to exemplify their variabilities, (2) analysing the variabilities of log K _OW estimates by underlying methods and for different chemical classes, and (3) recommending approaches to obtain reliable and robust log K _OW estimates for hazard and risk assessment. Results: Comparative analyses were based on 239 case study chemicals representing diverse chemical classes, such as POPs, PCB, PAH, siloxanes, flame retardants, PFAS, pesticides, pharmaceuticals, surfactants, etc. The variability of up to 35 log K _OW values per substance, determined experimentally or estimated by different computational approaches, is 1 log unit and more across the entire log K _OW range from < 0 to > 8. No systematic pattern is evident. Different methods for deriving log K _OW perform sometimes better and sometimes worse for different chemicals. None of the methods (experimental or computational) is consistently superior and any method can be the worst. Conclusions: For scientifically valid and reproducible log K _OW estimates with known variability, we recommend a weight-of-evidence (WoE) or averaging approach combining multiple estimates. Consolidated log K _OW , being the mean of at least 5 valid data obtained by different independent methods (experimental and computational), are a pragmatic way to deal with the variability and uncertainty of individual results. While this approach does not solve any of the problems about “correctly” determining log K _OW , it does limit the bias due to individual erroneous estimates. Consolidated log K _OW are robust and reliable measures of hydrophobicity, with variability mostly below 0.2 log units.