Water solubility is a fundamental parameter for the environmental risk assessment of organic chemicals. It is critical for understanding and predicting the environmental fate of substances, and also has relevance for their effect assessment. While water solubility is relatively easy to determine for some substances, it is much more difficult for other substances. In the present project we will address these difficulties in a systematic manner, with the overall goals to (1) facilitate progress within solubility research and testing, (2) develop and optimize methodology for determining solubility of difficult to test substances and (3) conduct ring testing and cross validations of existing and new methods. It is important to realize that there are challenges on the technical, analytical and scientific level, and several of these challenges will be addressed in the proposed project. Technically, it can be very challenging to generate a saturated aqueous solution of a chemical while ensuring the absence of the pure substance in crystal or liquid form and also the absence of substance bound to a third phase in the solution. The best way to address this issue is the careful selection and optimization of the physical principle to introduce the chemical into the solution. The proposed project will include a number of established and novel principles for introducing the test substance and saturating the water. The latest developments within passive dosing will be applied, and particularly the simple saturation of polymer by swelling in pure liquid phase and accelerated passive dosing that can provide equilibrated solutions within a few minutes. Analytically, it can be very challenging to measure aqueous concentrations in relatively small water volumes particularly for the most hydrophobic chemicals. We will address this challenge by a careful alignment of the solubility experiments and the subsequent analytical measurement of the aqueous concentration. Scientifically, there are several critical issues. (1) While solubility is well defined for single chemicals, many chemicals are produced, used and released into the environment as mixtures. Special attention will be given to how to address and determine solubility parameters for UVCBs, isomeric mixtures and enantiomeric mixtures. (2) For surfactants, the upper concentration limit for the dissolved molecules is given by the critical micelle concentration (CMC). CMCs of surfactants will be determined with a new analytical principle, which takes advantage of that free surfactant molecules behave as co-solute while micelles act as a third binding phase (Gouliarmou et al, 2012). (3) The existence of a well-defined solubility that sets the upper limit for aqueous concentrations in the environment can even be challenged, since super-saturated aqueous solutions are physically possible (Goss and Endo, 2016). While supersaturation of organic substances is a rare and less important phenomena within the environment, it is more likely to occur when spiking substances using water miscible solvents. We will not study supersaturation in detail, but rather aim for confirming the absence of supersaturation in our experiments. Aqueous solubility at a given condition should be physically and chemically defined, rather than by the method that was applied to measure it. However, since there are differences between experimental methods and also between prediction methods, aqueous solubilities will sometimes become operationally defined. Comparisons between different methods will be applied for studying and quantifying differences and hopefully cross validating the best methods. Ring testing will be applied to test the reproducibility and repeatability of selected methods.
The identification and scientific assessment of compounds that bioaccumulate in organisms and biomagnify in food webs are important aspects in the regulation of chemicals in several jurisdictions, such as Regulation (EC) No 1107/2009, the Regulation on classification, labelling and packaging of substances and mixtures, and the Regulation concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).
The additional information and insight gained through the application of toxicokinetic-toxicodynamic (TKTD) modelling can strengthen the environmental risk assessment of chemicals, such as those applied in consumer products or plant protection products (PPPs). For the endpoint survival the most suitable and powerful tool is currently the General Unified Threshold model of Survival (GUTS), which consists of two complimentary models: GUTS-SD (stochastic death) and GUTS-IT (individual tolerance).
The objective of this project is to further develop RVis, a prototype application for the analysis of structure and performance of physiologically based pharmacokinetic (PBPK), and other models, written in the free, open source syntax R or C++. The overall aim is to extend, improve and to provide more features and make them more robust.
The general objective of this proposed research is therefore to validate the combined use of (a) measured partition coefficients, (b) in vitro intrinsic hepatic clearance rates, and (c) a recently improved bioaccumulation model for ionogenic compounds, against measured bioconcentration factors of surfactants in fish.
This project aims to develop a user-friendly organizational framework and computational tool in the form of an Excel spreadsheet for integrating various lines of evidence in a quantitative weight of evidence (QWOE) approach to aid regulatory decision-making for bioaccumulation assessment.
The objective of this project is to bundle existing expertise to progress exposure assessment in in vitro bioassays used for high-throughput screening (HTS) in 384- and 1536-well plates and complex in vitro bioassays based on transwell and 3D cultures.
The purpose of this project is to develop criteria and examples (case studies) that can be applied to evaluate if exposure measurements for a given substance(s) and use scenario(s) might be reasonably representative for another substance used in the same or similar manner, as well as for the same substance in other use scenarios. The goal is to develop a pragmatic and agreed process for incorporating existing exposure measurement data on chemical substances (that have been obtained experimentally as opposed to modelled estimates) into worker exposure assessments that are typically undertaken in support of chemicals regulations.
This project aims to assess the ability of currently available new approach methodologies (NAM) to predict STOT-RE categories of a range of chemicals for which both in vitro and in vivo data are available and that can be profiled in silico.
The overall objective of the proposed research is to improve the interpretation of dietary bioaccumulation tests for hydrophobic chemicals.