COSMO-RS solute partition ratios for solvent mixtures of unknown composition: Henry's law constants as descriptors for mixture sigma profiles.

Henry's law constants (H) for selected probe molecules have been used as descriptors to estimate the COSMO-RS sigma profiles of solvents and solvent mixtures. Henry's law constants were calculated with COSMOtherm for small sets of probe molecules in 155 organic solvents (training set), and these constants subsequently used as descriptors to model the solvent sigma profiles with 61 multiple linear regression (MLR) equations. Subsequent input into COSMOtherm of weighted basis molecule solvent mixtures whose sigma profiles closely matched those modelled for the training set solvents allowed estimation of air-solvent and water-solvent partition ratios for solutes in solvents and solvent mixtures without input of the solvent or solvent mixture identity. The best performing model had 16 descriptors and gave both a training and test set average root-mean square error (RMSE) of 0.008 and an average relative square error (RSE) of 0.07. Partition ratios (K) were then generated for a test set of 251 additional organic solute molecules in solvent/water media where solvents were test set compounds and H constants for the same probe molecules were used as descriptors. The best performing sigma profile model yielded log K RMSE values ranging from 0.17 to 0.92. Finally, this approach was applied to several mixtures ranging from simple binary mixtures to two mixtures considered to be of unknown or variable composition, complex reaction productions or biological materials (UVCBs), namely gasoline and an essential oil mixture. Mixture/water partition ratios were estimated for 251 solutes giving log K RMSE values ranging from 0.24 to 0.88.

Indoor Dust/Air Partitioning: Evidence for Kinetic Delay in Equilibration for Low-Volatility SVOCs.

Effective modeling of semivolatile organic chemical (SVOC) partitioning between air and indoor dust is investigated by calculating partition ratios for selected SVOCs between air and n-octanol as well as 8 other oligomers similar in chemical structure to common components of household dust. COSMO-RS solvation theory was used to calculate air-oligomer partition ratios, which were converted to estimates for KOA (octanol-air) and Kdust-air. The results are compared with reported monitored partition ratios with good agreement for the more volatile SVOCs of vapor pressure (VP) exceeding 10-5 Pa and corresponding calculated log Kdust-air (m3 g-1) of <5.5 or unitless log KOA of <11.5. For less volatile SVOCs, reported values of KDA are significantly lower than predicted, with the deviation increasing with decrease in VP. This effect is attributed to a kinetic delay in which characteristic times for equilibration exceed the dust-air contact time, and equilibrium is not achieved. It is hoped that the approach of computing partition ratios of SVOCs using oligomers selected on the basis of likely dust sources and compositions may improve the estimation of indoor human exposure to SVOCs present in air and dust and assist in exploiting dust samples to monitor and evaluate the fate and exposure of organic chemicals used indoors.

A perspective on the role of fugacity and activity for evaluating the PBT properties of organic chemicals and providing a multi-media synoptic indicator of environmental contamination.

The hazard and risk from organic chemicals present in the environment are routinely evaluated using P (persistence), B (bioaccumulation) and T (toxicity) criteria. We present a perspective on how models based on the equilibrium criteria of fugacity and chemical activity can contribute to all three evaluations, thus providing a consistent and seamless assessment process. Persistence and its closely related, but fundamentally different property, chemical residence time can be determined from degradation half-lives (typically obtained from monitoring data) and multi-media mass balance models describing chemical fate and transport in real or evaluative environments. Bioaccumulation is driven by equilibrium partitioning processes that can be estimated from fugacity models treating uptake by respiration and diet in single organisms and in food webs, most commonly for aquatic systems for which confirmatory monitoring data can be obtained. Biomagnification is readily evaluated both experimentally and as a fugacity (or activity) increase from prey to predator. Toxicokinetic evaluations of chemical uptake and disposition in a variety of organisms, including humans, can be obtained using fugacity- and physiologically-based pharmacokinetic models. Toxicodynamic processes of chemical interactions with organisms leading to adverse toxic outcomes are less obviously amenable to fugacity assessment with the notable exception of baseline toxicity (narcosis), the most common mode of action of commercial chemicals. It is shown that a range of fugacities can be defined and correlated for specific species thus enabling direct comparison of fugacities estimated or monitored in the environment with fugacities resulting in baseline toxicity. Finally, it is shown that fugacity and activity can serve as multi-media metrics of chemical contamination in ecosystems, thus enabling identification of specific regions and species at greatest risk in a pictorial format that is readily understandable to scientific and regulatory communities and to the general public.

Kinetic Delay in Partitioning and Parallel Particle Pathways: Underappreciated Aspects of Environmental Transport.

We outline the general conditions under which chemicals of high hydrophobicity or, more generally, high partition ratios (HPRs) in water or air, may experience unexpectedly long kinetic delays in approaching equilibrium conditions with organic media. Such a "hydrophobic delay" in the case of K OW or an "aerophobic" delay in the case of KOA may be misinterpreted as being caused by a change in partitioning behavior or mechanism, resulting in development of nonlinear regression models describing intermedia partitioning. In fact, the partitioning is fundamentally linear but is distorted by a kinetic delay in partitioning. To illustrate this concept, we first compile the fundamental equations describing the diffusive equilibration processes, including a complementary transport mechanism termed a parallel particle pathway (PPP). Such a mechanism may occur simultaneously, shortening the HPR delay and complicating interpretation. Second, we describe five examples in which the HPR delay explains the observed and occasionally difficult-to-interpret environmental behavior of chemicals, namely studies of air-aerosol partitioning, chemical accumulation in indoor dust and surfaces, air-vegetation partitioning, internal transport in organisms, and fish bioaccumulation and toxicity. We believe that the general HPR delay and PPP issues deserve exposure as a commonly occurring and often underappreciated process.

Bioconcentration, bioaccumulation, biomagnification and trophic magnification: a modelling perspective.

We present a modelling perspective on quantifying metrics of bio-uptake of organic chemicals in fish. The models can be in concentration, partition ratio, rate constant (CKk) format or fugacity, Z and D value (fZD) format that are shown to be exactly equivalent, each having it merits. For most purposes a simple, parameter-parsimonious one compartment steady-state model containing some 13 parameters is adequate for obtaining an appreciation of the uptake equilibria and kinetics for scientific and regulatory purposes. Such a model is first applied to the bioaccumulation of a series of hypothetical, non-biotransforming chemicals with log KOW (octanol-water partition ratio) values of 4 to 8 in 10 g fish ranging in lipid contents to deduce wet-weight and lipid normalized concentrations, bioaccumulation and biomagnification factors. The sensitivity of biomagnification factors to relative lipid contents is discussed. Second, a hypothetical 5 species linear food chain is simulated to evaluate trophic magnification factors (TMFs) showing the critical roles of KOW and biotransformation rate. It is shown that lipid normalization of concentrations is most insightful for less hydrophobic chemicals (log KOW < 5) when bio-uptake is largely controlled by respiratory intake and equilibrium (equi-fugacity) is approached. For more hydrophobic chemicals when dietary uptake kinetics dominate, wet weight concentrations and BMFs are more insightful. Finally, a preferred strategy is proposed to advance the science of bioaccumulation using a combination of well-designed ecosystem monitoring, laboratory determinations and modelling to confirm that the perceived state of the science contained in the models is consistent with observations.

The chemical exposure toxicity space (CETS) model: Displaying exposure time, aqueous and organic concentration, activity, and onset of toxicity.

A 1-compartment toxicokinetic model is used to characterize the chemical exposure toxicity space (CETS), providing a novel graphic tool that can aid in the design of aquatic toxicity tests for fish and for interpreting their results. The graph depicts the solution to the differential equation describing the uptake kinetics of a chemical by a modeled fish under conventional bioassay conditions. The model relates the exposure concentration in the water to a dimensionless time and the onset of toxicity as determined by an estimated or assumed critical body residue or incipient lethal aqueous concentration. These concentration graphs are specific to each chemical and exposure and organism parameters and clearly demonstrate differences in toxicity between chemicals and how factors such as hydrophobicity influence the toxic endpoint. The CETS plots can also be used to assess bioconcentration test conditions to ensure that concentrations are well below toxic levels. Illustrative applications are presented using a recent set of high-quality toxicity data. Conversion of concentrations to chemical activities in the plots enables results for different baseline toxicants to be superimposed. For chemicals that have different modes of toxic action, the increased toxicity then becomes apparent. Implications for design and interpretation of aquatic toxicity tests are discussed. The model, and pictorial visualization of the time-course of aquatic toxicity tests, may contribute to improvements in test design, implementation, and interpretation, and to reduced animal usage. Environ Toxicol Chem 2017;36:1389-1396. © 2016 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC.

Processes influencing chemical biomagnification and trophic magnification factors in aquatic ecosystems: Implications for chemical hazard and risk assessment.

Bioconcentration factors (BCFs) and bioaccumulation factors (BAFs) are widely used in scientific and regulatory programs to assess chemical hazards. There is increasing interest in also using biomagnification factors (BMFs) and trophic magnification factors (TMFs) for this purpose, especially for highly hydrophobic substances that may reach high concentrations in predatory species that occupy high trophic level positions in ecosystems. Measurements of TMFs in specific ecosystems can provide invaluable confirmation that biomagnification or biodilution has occurred across food webs, but their use in a regulatory context can be controversial because of uncertainties related to the reliability of measurements and their regulatory interpretation. The objective of this study is to explore some of the recognized uncertainties and dependencies in field BMFs and TMFs. This is accomplished by compiling a set of three simple food web models (pelagic, demersal and combined pelagic-demersal) consisting of up to seven species to simulate field BMFs and TMFs and to explore their dependences on hydrophobicity (expressed as log KOW), rates of biotransformation and growth, sediment-water fugacity ratios, and extent of food web omnivory and issues that arise when chemical concentration gradients exist in aquatic ecosystems. It is shown that empirical TMFs can be highly sensitive to these factors, thus the use of TMFs in a regulatory context must recognize these sensitivities. It is suggested that simple but realistic evaluative food web models could be used to extend BCF and BAF assessments to include BMFs and TMFs, thus providing a tool to address bioaccumulation hazard and the potential risk of exposures to elevated chemical concentrations in organisms at high trophic levels.

A fugacity-based toxicokinetic model for narcotic organic chemicals in fish.

A novel dynamic fugacity-based model is described, developed, and tested that simulates the uptake of narcotic organic chemicals in fish from water as occurs in aquatic bioconcentration and toxicity tests. The physiologically based toxicokinetic model treats the time course of chemical distribution in 4 compartments (tissue groups) in the fish, including the liver, in which biotransformation may occur. In addition to calculating bioconcentration and toxicokinetics, 5 possible toxic endpoints are defined corresponding to chemical concentration, fugacity, or activity reaching a critical value that causes 50% mortality. The mathematical description of multicompartment uptake is simplified by expressing the equations in the fugacity format. The model is parameterized and tested against reported empirical data for the bioconcentration of pentachloroethane in rainbow trout and for uptake and mortality from aquatic exposures to naphthalene and 1,2,4-trichlorobenzene in fathead minnows. Model performance is evaluated, and it is concluded that with suitable parameterization it has potential for application for assessment of both bioconcentration and toxicity expressed as median lethal concentrations, critical body residues, and chemical activity as a function of time to death.

Impact of temperature, pH, and salinity changes on the physico-chemical properties of model naphthenic acids.

The effects of temperature, pH, and salinity change on naphthenic acids (NAs) present in oil-sands process wastewater were modeled for 55 representative NAs. COSMO-RS was used to estimate octanol-water (KOW) and octanol-air (KOA) partition ratios and Henry's law constants (H). Validation with experimental carboxylic acid data yielded log KOW and log H RMS errors of 0.45 and 0.55 respectively. Calculations of log KOW, (or log D, for pH-dependence), log KOA and log H (or log HD, for pH-dependence) were made for model NAs between -20 °C and 40 °C, pH between 0 and 14, and salinity between 0 and 3 g NaCl L(-1). Temperature increase by 60 °C resulted in 3-5 log unit increase in H and a similar magnitude decrease in KOA. pH increase above the NA pKa resulted in a dramatic decrease in both log D and log HD. Salinity increase over the 0-3 g NaCl L(-1) range resulted in a 0.3 log unit increase on average for KOW and H values. Log KOW values of the sodium salt and anion of the conjugate base were also estimated to examine their potential for contribution to the overall partitioning of NAs. Sodium salts and anions of naphthenic acids are predicted to have on average 4 log units and 6 log units lower log KOW values, respectively, with respect to the corresponding neutral NA. Partitioning properties are profoundly influenced by the by the relative prevailing pH and the substance's pKa at the relevant temperature.