When to Use QSAR for Chemical Substance Registration and Common QSAR Models

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. 

When to Use QSAR

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.

Example 1: Increasing the acceptance of data generated in non-GLP labs

(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.

Example 2: Developing testing strategy and supporting the waiver of higher tier studies

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.

Example 3: Providing data when testing is not technically possible

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).

Example 4: Screening the toxicity of new molecules

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. 

Example 5: Prioritization of existing chemical substances for further assessment

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. 

Common QSAR Models

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

  • Danish QSAR Database 
  • ACD/Percepta (ACD/Labs) - Commercial
  • ADMET Predictor (Simulations Plus) - Commercial
  • JChem (ChemAxon) - Commercial

Henry's law constant


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

  • OECD QSAR Toolbox
  • ToxTree (JRC)
  • CASE Ultra (MultiCASE) - Commercial
  • ACD/Percepta (ACD/Labs) - Commercial
  • Discovery Studio (Accelrys) - Commercial
  • Derek (Lhasa) - Commercial

Skin sensitisation

Repeated dose toxicity

  • Derek (Lhasa) - Commercial
  • ADMET Predictor (Simulations Plus) - Commercial
  • CASE Ultra (MultiCASE) - Commercial

In vitro gene mutation in bacteria (Ames test)

Mutagenicity (other endpoints than in vitro gene mutation in bacteria)

Reproductive toxicity

  • Danish QSAR Database 
  • ToxTree (JRC)
  • ADMET Predictor (Simulations Plus) - Commercial
  • CASE Ultra (MultiCASE) - Commercial
  • Discovery Studio (Accelrys) - Commercial
  • Derek (Lhasa) - Commercial
  • Leadscope - Commercial

Take-home Message

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. 


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 Tags: Topics - CRAREACH-like Regulation and Registration