Little Pro on 2017-08-17
Structure-activity relationship (SAR) and quantitative structure-activity relationship (QSAR) models are theoretical models that can be used to quantitatively or qualitatively predict the physicochemical, biological (e.g. an (eco) toxicological endpoint) and environmental fate properties of a chemical substance from the knowledge of its chemical structure. Despite the fact that most of regulators prefer actual measured data over QSAR prediction, the usefulness of QSAR should not be underestimated. In this article, we will show you when to QSAR for chemical substance registration and provide a list of common QSAR models accepted by regulators.
It is true that (Q)SAR prediction results are usually only accepted when they are used as part of a weight of evidence (WoE) approach or as supporting information. They cannot fully replace actual testing. However, (Q)SAR’s role in chemical substance registration and risk assessment cannot be ignored. Let me give you 4 examples about the usefulness of QSAR models.
(Q)SAR predictions can increase the acceptance of study results from tests that have not been performed according to good laboratory practice (GLP) or according to accepted guidelines. If QSAR predictions are consistent with the experimental results, the results are more likely to be accepted.
There are lots of reliable QSAR models that can be used to predict logKow and Bio-concentration factor (BCF). If the predicted logKow (i.e, logKow<3) or predicted BCF is very low, you may use this justification to strengthen your waiver of a high-tier bio-accumulation study.
QSAR can also be used to provide data when testing is not technically possible. Such data may include vapor pressure, aquatic toxicity data and some e-fate properties (e.g.atmospheric oxidation and hydrolysis).
Lots of pharmaceutical companies and pesticide companies also use QSAR models to screen the toxicity (i.e, acute toxicity, mutagenicity, carcinogenicity) of new molecules and decide which molecule to be prioritized for commercialization.
For many existing substances on the market, there is no complete hazard dataset. QSAR estimations can be used to differentiate hazardous substances from less hazardous substances. This is very useful for prioritizing existing substances for further risk assessment.
The table below summarizes which chemical properties can be estimated by QSAR and commonly used QSAR models.
Endpoints | QSAR Models |
---|---|
Melting point, boiling point, water solubility |
|
Relative density, surface tension, flash point, vapor pressure, thermal conductivity, viscosity |
|
Partition coefficient (log Kow) |
|
Dissociation constant pKa |
|
Henry's law constant |
|
Hydrolysis |
|
Ready biodegradability |
|
Bioaccumulation in aquatic species |
|
Adsorption/desorption screening - Koc |
|
Short-term toxicity to fish (LC50, 96h) |
|
Long-term toxicity to fish |
|
Short-term toxicity to aquatic invertebrates (daphnia) (EC50/LC50, 48h) |
|
Long-term toxicity to aquatic invertebrates (daphnia) - ChV |
|
Toxicity to aquatic plants (algae) |
|
Short-term toxicity to terrestrial invertebrates (14d, earthworm LC50) |
|
Acute toxicity |
|
Skin irritation or skin corrosion |
|
Eye irritation |
|
Skin sensitisation |
|
Repeated dose toxicity |
|
In vitro gene mutation in bacteria (Ames test) |
|
Mutagenicity (other endpoints than in vitro gene mutation in bacteria) |
|
Reproductive toxicity |
|
The role of QSAR models in chemical registration and risk assessment shall not be underestimated. The most frequently used free QSAR models for physio-chemical properties are US EPA EPI Suite and US EPA TEST. For aquatic toxicity data, Danish QSAR database and US EPA ECOSAR are frequently used. For toxicity endpoints, US EPA TEST, ToxTree, OECD QSAR Toolbox and Danish QSAR database are available for use.
We will show you how to use those QSAR models in our next tutorial. Please subscribe to our newsletter to receive updates about new articles and tutorials.
We do not provide consultancy services. If you have questions or need any help, please contact our sponsor. You may also find an expert in CSP business directory below. If you are a consultant, you may get yourself listed in CSP business directory (free) or sponsor this page to leave your contact info on this page..