1. Using Derek Nexus to assess the safety of raw materials used in cosmetics and as part of a skin sensitisation ITS.
Part 1: Using Derek Nexus to assess the safety of raw materials used in cosmetics.
Alison Reeves
Sales Executive

2. Agenda Who are Lhasa Limited? Derek Nexus
Where are our members based?
Derek Nexus
What is Derek Nexus?
Why should you use Derek Nexus?
How does Derek Nexus work?
A Derek Nexus Prediction Explained
What does a prediction look like?
How to interpret a prediction
Skin Sensitisation/ EC3 Predictions in Derek Nexus.

3. Who are Lhasa Limited? Not-for-profit organisation Educational Charity
Controlled by our members
Knowledge base and database systems
Lhasa est. 1983
Used to be right next to Leeds University
Still have close ties to the university
Not for profit
Not a customer – a member
Sponsor the continued development of the software
As such have a say in what we do - vICGMs etc.
This is an important factor, we are not likely to be bought out by other companies
Encourages the sharing of data – it’s safe
Educational charity
Can offer large discounts to educational and government funded organisations etc (of approx 85%)
Also sponsor work of PhD students etc. – some of which go on to become members of staff at Lhasa
We offer 5 programs at the moment – rewritten recently into Java Eclipse
Sarah – NEW – Mutagenicity QSAR
Zeneth – 5yrs – forced degradation
Vitic – 8yrs – chem database
Meteor – 17yrs – metabolism- predicts metabolites
Derek – MOST 25yrs – toxicity prediction tool

4. 339 Lhasa Members
332 dx sites
Derek users -product with the most uptake, global use
Almost 300 users
Mostly European and North American
Growth in Japan and now China which are sold through software licensing agents. India is also a growing market.
70% pharma users – biotechs/pharma/generics companies
Chemical, agrochemical used for REACH
Cosmetics and Perfumeries
Personal products
Tobacco
Medical devices
Universities
Regulatory – ECHA and FDA are users
Top 20 pharma use our software, the likes of Pfizer, GSK etc as you can see at the top of this screen

5. What is Derek Nexus? Toxicity prediction tool
Knowledge-based expert system
Broad range of toxic endpoints
Identifies toxicophores
Makes qualitative predictions
KB/expert system, the KB is data that has been compiled and processed by Lhasa’s database scientists (human experts)
Lhasa certified database of toxicological endpoints, always growing and developing- don’t just focus on mutagenicity ~65 end points at the moment
Alerts within the KB recognise the specific patterns of toxicophores in compounds ~810 alerts within KB atm
As opposed to making a quantitative prediction such as a percentage conviction etc. gives a qualitative prediction between Impossible and Certain.
Impossible – Improbable - Doubted – Equivocal – Plausible – Probable - Certain

6. Why use Derek Nexus?
Implementation of EU Regulation 1223/2009 (Cosmetics Regulation) has led to increased interest in non-animal alternatives
Build toxicity profiles
Quick & easy to use
No limit on number of predictions
KB/expert system, the KB is data that has been compiled and processed by Lhasa’s database scientists (human experts)
Lhasa certified database of toxicological endpoints, always growing and developing- don’t just focus on mutagenicity ~65 end points at the moment
Alerts within the KB recognise the specific patterns of toxicophores in compounds ~810 alerts within KB atm
As opposed to making a quantitative prediction such as a percentage conviction etc. gives a qualitative prediction between Impossible and Certain.
Impossible – Improbable - Doubted – Equivocal – Plausible – Probable - Certain

7. How does Derek Nexus work? -Knowledge base search
Molecular
weight
Metabolic
activation
Skin permeability
Presence of
toxicophore
So taking this same structure we can see that we have highlighted the toxicophore
Derek consists of a Knowledge Base and a reasoning engine. The knowledge base contains structure activity relationships.
Once a query structure is inputted and constraints set, the program searches the Knowledge Base for any matches between substructures in the query molecule and sub structures it knows are linked to structure-activity relationships.
The toxic likelihood is based on absolute reasoning rules which are in turn based on the species you have selected, skin permeability, molecular weight, etc.
Log P- generated by external party, C log P
The Knowledge base currently consists of over 300 structure-activity relations that have been derived by searching literature, using published databases & collaborative group suggestions or donations.
Species

8. What does a prediction look like?
Example compound: ISOEUGENOL Taken from: SCCS (Scientific Committee on Consumer Safety), opinion on fragrance allergens in cosmetic products, December 2011

18. Skin Sensitisation & EC3 Predictions in Derek Nexus.
Skin sensitisation alerts will now give an additional EC3 prediction (extending hazard to risk)
EC3 values correlate well with human sensitisation induction thresholds
EC3 values are then binned into potency categories:
the current version containing 88 skin sensitisation alerts.
The LLNA gives an EC3 value to give a quantitative potency prediction
Skin sensitisation alerts have been expanded to provide positive predictions. Once a compounds fires a skin sensitisation alert an addition tab will now appear (demonstration later). This will now produce an EC3 value to help quantify the skin sensitisation endpoint.
As stated the EC3 is a valuable parameter as it comes from the LLNA (end of the line assay etc). Another advantage is that is gives a dose response from multiple points, so rather than being an opinion from a scientist it is a quantitative measure as oppose to a qualitative method (looking at the side of a shaved guinea pig and trying to decide if it is a weak or moderate sensitizer). These EC3 values correlate well with human sensitisation induction thresholds and can be binned into potency categories. *Also worth noting that other potency categories such as the GHS categories exist. If this is the case you can demonstrate how the potency category can be turned off and just the EC3 value generated.
GHS classifications are as follows: GHS 1A =< 2%; GHS 1B > 2%; GHS 2 = non-sensitiser

23. To summarise: What I hope you have gained…
An overview of how Derek Nexus can help you to build toxicity profiles for your cosmetic ingredients
An insight into how Derek Nexus works
An understanding of how to run and interpret a prediction
A flavour of EC3 Predictions in Derek Nexus
If you would like to arrange a further demonstration of Derek Nexus please do not hesitate to contact me.

24. Thank you very much for listening. Do you have any questions
Thank you very much for listening. Do you have any questions? Next: Part 2: Using Derek Nexus as part of a skin sensitisation ITS.

25. Part 2: Using Derek Nexus as part of a skin sensitisation ITS.
Using Derek Nexus to assess the safety of raw materials used in cosmetics and as part of a skin sensitisation ITS.
Part 2: Using Derek Nexus as part of a skin sensitisation ITS.
Dr Donna Macmillan
Scientist

26. Work in progress disclaimer
This document is intended to outline our general product direction and is for information purposes only, and may not be incorporated into any contract. It is not a commitment to deliver any material, code, or functionality, and should not be relied upon. The development, release, and timing of any features or functionality described for Lhasa Limited’s products remains at the sole discretion of Lhasa Limited.