1. Information Sources Day 1.
Adam Peters and Graham Merrington
2017

2. Information
SMILES
QSAR
Tests
Reliability
Fate
2017

3. Information Sources
ECHA dissemination portal
2017

4. Predicting Chemical Properties
USEPA EPI Suite – suite of QSAR models
Generally suitable for non-ionisable organic chemicals
Structures for most substances available in a database
SMILES codes may be available on the internet
Derive the SMILES code yourself
Always check that the structure produced is the substance you are working on
2017

5. SMILES Codes Simplified Molecular-Input Line-Entry System
Summarises the molecular structure in a way which can be entered into a model
Try to join every atom with a single continuous line
Cyclohexane or benzene?
End
Start
2017

6. EPI Suite
2016

7. EPI Suite Outputs Original Structure SMILES from structure
CN1C(=O)N(C)C(=O)c2N(C)C=Nc12
SMILES from CAS RN
CN1C(=O)N(C)c2ncn(C)c2C1(=O)
SMILES codes are not unique, they could start (and end) at any part of the structure.
Both sets of predictions resulted in the same structure despite different notations
2017

8. EPI Suite Predictions Log KOW, from structure
Vapour pressure, from structure
Water solubility, from KOW & structure (2 models)
Baseline toxicity (apolar narcosis)
Henrys Law Constant
KOC, from KOW & structure (2 models)
Biodegradation (readily biodegradable?)
Based on results of several models
2017

9. Test Methods Usually according to OECD standard tests
Different methods depending upon nature of the substance (e.g. solubility in solvents)
May be limited by analytical capabilities
Water solubility in pure water may be quite different to solubility in natural waters
There is an upper limit to measureable values of log KOW due to the solubility of water in octanol and vice versa
2017

10. Reliability of Information
Original study reports may not be available
There may be several studies for a single endpoint
Critical study or weight of evidence?
Justification and recording of decisions made can be critical because some parameters can have a large influence on risk assessment outcomes
2017

11. Partitioning Indicated by log KOW, log KOC, and KD
Usually assumed to be controlled by organic carbon content of medium (soil/sediment)
Limited predictability for substances with no reliable log KOW value
Empirical measurements usually required for ionisables, inorganics, and metals
Can be highly variable between different environments
2017

12. Ionisable Organic Substances
Tend to behave differently to non-polar substances in the environment
Properties tend not to be predictable by QSAR
Often identifiable from the structure of the substance
Dissociation constant – pKa
pKa is equal to the pH at which both forms (ionised and unionised) of the substance (or functional group) are present at equal concentrations
2016

13. Partition Coefficients for Ionisable Substances
May be measured in buffered solutions
Several pH levels may need to be tested
Should cover a range of ionisation of the substance
Substances may have more than one ionisable functional group
Amino acids have at least 2 ionisable functional groups
-COOH, and –NH2
Ionisation affects water solubility
2016

14. Degradation Ready biodegradability test
Rapid mineralisation under favourable conditions
Usually limited other test data
Important to distinguish between mineralisation (to CO2 and H2O) and primary degradation (original substance not present)
Degradation products are usually more soluble and more degradable than the original substance
2017

15. Bioaccumulation Accumulation in biota and food chains
Indicated by partition coefficient
Bioconcentration factor BCF
Accumulation from water
Bioaccumulation factor BAF
Accumulation from both food and water
Biomagnification factor BMF
Accumulation from food
2017

16. 2016