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

Abstract

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 231 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 36 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

Iterative consensus modelling combines multiple estimates by a weight-of-evidence (WoE) or averaging approach for scientifically valid and reproducible log K_OW estimates with known variability. 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 within 0.2 log units.