Determining the water solubility of difficult-to-test substances: A tutorial review

Area of Science:

• Environmental Chemistry
• Physical Chemistry
• Chemical Analysis

Background:

• Water solubility is a critical physicochemical property for chemical safety and risk assessment.
• Current OECD guidelines for solubility testing are outdated and unsuitable for many complex substances.
• Difficult-to-test chemicals like highly hydrophobic substances, volatile compounds, surfactants, and mixtures pose challenges for standard solubility measurements.

Purpose of the Study:

• To review and present technical, analytical, and scientific methods for measuring water solubility in difficult-to-test substances.
• To address limitations of existing OECD guidelines for specific chemical categories.
• To provide a comprehensive overview of solubility determination strategies for a range of challenging chemical types.

Main Methods:

• Review of existing literature and OECD guidelines on solubility measurement.
• Analysis of methods tailored for highly hydrophobic and volatile chemicals.
• Examination of techniques for rapidly saturating water with rapidly degrading chemicals.
• Inclusion of methods for determining critical micelle concentrations (CMCs) for surfactants.
• Discussion of strategies for measuring solubility parameters in mixtures and multi-constituent substances.

Main Results:

• Identified specific methods suitable for highly hydrophobic and volatile chemicals.
• Reviewed techniques for handling fast-degrading substances.
• Presented methods for critical micelle concentration determination.
• Discussed approaches for assessing solubility in complex mixtures.
• A decision tree is proposed to guide method selection for different chemical groups.

Conclusions:

• Existing OECD guidelines are insufficient for many complex chemical substances.
• A range of advanced methods are available to accurately measure water solubility for difficult-to-test chemicals.
• The presented review and decision tree offer valuable guidance for selecting appropriate solubility testing strategies.