The In Vitro assessment of Respiratory Sensitisation Potential of Electronic Cigarette Liquids

Matthew Stevenson, Lukasz Czekala, Liam Simms, Nicole Tschierske, Henrik Johansson, Tanvir Walele Imperial Tobacco Ltd, Reemtsma Cigarettenfabriken GmbH, an Imperial Brands PLC Company, SenzaGen AB, Fontem Ventures B.V., an Imperial Brands PLC Company,   Introduction and Objectives There is a general consensus amongst the scientific and public health community that e-cigarettes constitute a less harmful source of nicotine […]

Matthew Stevenson, Lukasz Czekala, Liam Simms, Nicole Tschierske, Henrik Johansson, Tanvir Walele
Imperial Tobacco Ltd, Reemtsma Cigarettenfabriken GmbH, an Imperial Brands PLC Company, SenzaGen AB, Fontem Ventures B.V., an Imperial Brands PLC Company,

 

Introduction and Objectives

There is a general consensus amongst the scientific and public health community that e-cigarettes constitute a less harmful source of nicotine than combustible cigarettes, and that flavours play a critical role in attracting and retaining smokers into the vaping category. Due to the dynamic nature of innovation with e-cigarettes new assays are required to quickly determine the subtle biological response of these products for product stewardship activities. The size of this task is considerable as recent estimates state that more than 8,000 e-liquid flavours are on the market (Hartung, 2016). One particular toxicological endpoint which is of interest for the Stewardship of e-liquids, is Respiratory Sensitisation.
Respiratory sensitization (RS) is an allergic type I hypersensitivity reaction of the upper and lower respiratory tract caused by an immune response triggered by low molecular weight compounds or other environmental proteins. Clinical symptoms of RS include asthmatic attacks, bronchoconstriction and wheezing upon repeated exposure to the same compound. However, respiratory sensitisers are rare, with around 100 well characterised substances described in the literature.
It is Fontem Ventures policy to screen all novel e-liquid ingredients for Respiratory sensitising activities using published literature and in silico techniques. However, there is a need for alternative techniques to fill data gaps and add to a weight of evidence. Several in vitro assays have been described and validated to assess skin sensitisation, however for respiratory sensitization there are no validated predictive assays. It is of note that not all skin sensitizers are also respiratory sensitizers. In 2015, Basketter and Kimber concluded that “…airborne fragrance materials, including skin sensitising fragrance materials, do not pose a risk of the induction or elicitation of allergic reactions consequent upon exposure via the respiratory tract”. Therefore, it is critical that any assays developed to determine the sensitising properties of a chemical can distinguish between dermal and respiratory activity.
The objective of this study was to assess experimental and commercial e-liquids in GARDair™; an assay which claims to detect respiratory sensitisers.
GARDair measures the genomic biomarker signature of a human myeloid leukemia-derived cell line exposed to test substances; making this technology in keeping with the 3Rs (Reduce, Replace and Refine) and Toxicity Testing in the 21st Century principles. Gene expression analysis is performed using Affymetrix microarray technology and a prediction model is used to classify each sample according to its respiratory sensitizing potential.

 

Conclusions

• From the Benchmark Control data it was estimated that GARDair™ had a sensitivity and specificity of 71% and 100% respectively; with an overall predictive accuracy estimated as 89%.
• Extensive validation of this assay is ongoing, however, the lack of well characterised Chemical Respiratory Sensitisers may limit this.
• None of the experimental or commercial samples were classified as respiratory sensitisers.
• Further exploration of this assay is required, particularly its ability to detect low concentrations of sensitiser in complex mixtures and to ensure that the e-liquid matrix does not interfere with the detection of activity.

Poster:
The In Vitro assessment of Respiratory Sensitisation Potential of Electronic Cigarette Liquids_British ToxSocCong 2018 Imperial

SenzaGen to present at Vator Securities Unicorn Summit on May 8, 2018

SenzaGen announces that the company will participate in the Vator Securities Unicorn Summit, which takes place in Stockholm in May. Anki Malmborg Hager, CEO, will present the company developments and SenzaGen’s ongoing and planned activities for commercialization of GARD – a technology platform that allows for replacement of animal experiments with genetic testing to assess […]

SenzaGen announces that the company will participate in the Vator Securities Unicorn Summit, which takes place in Stockholm in May. Anki Malmborg Hager, CEO, will present the company developments and SenzaGen’s ongoing and planned activities for commercialization of GARD – a technology platform that allows for replacement of animal experiments with genetic testing to assess whether the chemicals we come into contact with in our daily lives are allergenic.

Unicorn Summit is a capital market day organized by Vator Securities to bring together some of the most innovative and fast-growing Swedish life science companies with investors. More information about Vator Securities www.vatorsecurities.se

 

For more information, please contact:
Anki Malmborg Hager, CEO, SenzaGen AB
Email: anki.malmborg.hager@senzagen.com
Telephone: +46 768 284822

 

About GARD™
GARD is a group of tests for assessing chemical skin sensitizers. The tests make use of genetic biomarkers for more than 200 genes which cover the entire immune reaction and are relevant to predicting the risk of hypersensitivity. The tests have over 90 percent reliability.

This compares with the current predominant test method, experiments on mice, which has an accuracy of 70-75 percent. SenzaGen’s tests are also capable of measuring the potency of a substance’s allergenic properties. Consequently, GARD tests provide a much more comprehensive basis for determining whether a substance should be classified as an allergen than current testing methods.

About SenzaGen
SenzaGen makes it possible to replace animal experiments with in vitro genetic testing to determine the allergenicity of the chemicals we come into contact with in our daily lives, such as for example in cosmetics, pharmaceuticals, food products and dyes. The company’s patented tests are the most reliable on the market and provide more information than traditional evaluation methods. We ourselves sell the tests in Sweden and the USA, and we sell through partners in several other countries. Over the next few years the company will expand geographically, make alliances with more distribution partners and launch further unique tests. SenzaGen has its headquarters in Lund in Sweden and a subsidiary in San Francisco, USA. For more information visit www.senzagen.com

SenzaGen AB are listed on Nasdaq First North in Stockholm and FNCA is the company’s Certified Adviser. For more information, please visit www.senzagen.com

 

 

SenzaGen invites to a Live Session at the Facebook group “Aktier – Småbolagsjakten”

SenzaGen will host a live Question and Answer session with the management of the company May 16 between 19:00 – 20:00 CET “Aktier – Småbolagsjakten” is the largest Facebook group in the Nordic region, focusing on publicly traded small companies. The group has over 35 000 members. During the Live Session all questions and answers will […]

SenzaGen will host a live Question and Answer session with the management of the company May 16 between 19:00 – 20:00 CET

“Aktier – Småbolagsjakten” is the largest Facebook group in the Nordic region, focusing on publicly traded small companies. The group has over 35 000 members.

During the Live Session all questions and answers will be in English. Participants will have the opportunity to ask questions directly to company management including Chairman Carl Borrebaeck and CEO Anki Malmborg Hager.

To participate in the session, you must first become a member of the Facebook group “Aktier – Småbolagsjakten”. It is recommended that you submit a membership request at least one day in advance of the presentation to ensure you can participate in the event.

 

To join the group:

  1. Go to https://www.facebook.com/groups/smabolagsjakten
  2. Click the green “+ Join Group” button
  3. You will receive a notification on Facebook when your application to the group is accepted

 

For more information, please contact:
Anki Malmborg Hager, CEO, SenzaGen AB
Email: anki.malmborg.hager@senzagen.com
Telephone: +46 768 284822

 

About GARD™
GARD is a group of tests for assessing chemical skin sensitizers. The tests make use of genetic biomarkers for more than 200 genes which cover the entire immune reaction and are relevant to predicting the risk of hypersensitivity. The tests have over 90 percent reliability. This compares with the current predominant test method, experiments on mice, which has an accuracy of 70-75 percent. SenzaGen’s tests are also capable of measuring the potency of a substance’s allergenic properties. Consequently, GARD tests provide a much more comprehensive basis for determining whether a substance should be classified as an allergen than current testing methods.

About SenzaGen
SenzaGen makes it possible to replace animal experiments with in vitro genetic testing to determine the allergenicity of the chemicals we come into contact with in our daily lives, such as for example in cosmetics, pharmaceuticals, food products and dyes. The company’s patented tests are the most reliable on the market and provide more information than traditional evaluation methods. We ourselves sell the tests in Sweden and the USA, and we sell through partners in several other countries. Over the next few years the company will expand geographically, make alliances with more distribution partners and launch further unique tests. SenzaGen has its headquarters in Lund in Sweden and a subsidiary in San Francisco, USA. For more information visit www.senzagen.com

 

SenzaGen AB are listed on Nasdaq First North in Stockholm and FNCA is the company’s Certified Adviser. For more information, please visit www.senzagen.com

Successful outcome at the Future of Swedish and Danish Life Science day

We wish to thank Kemivärlden Biotech and Medicon Village for Thursday’s event “The Future of Swedish and Danish Life Science”, many interesting areas within precision medicine and big data were covered, not least within genomics. Life sciences and information technologies have become more and more connected to make patient’s life better; a perfect example on […]

We wish to thank Kemivärlden Biotech and Medicon Village for Thursday’s event “The Future of Swedish and Danish Life Science”, many interesting areas within precision medicine and big data were covered, not least within genomics.

Life sciences and information technologies have become more and more connected to make patient’s life better; a perfect example on this is SenzaGen’s in vitro safety testing based on genomics. By argumenting on how the company’s GARD™ technology can improve patient’s life, and how the technology can contribute to establish a new industry standard for animal free safety testing, SenzaGen’s Chief Commercial Officer, Anna Chérouvrier Hansson, won the Dragons Den pitch at The Future of Swedish and Danish Life Science.

-We’re very happy and proud to be recognized as a game changer in the industry, contributing to a safer patient environment, says Anna.
The prize, a ticket to the One Nucleus Genesis conference in London will support SenzaGen’s development of coming closer to the goal of placing a new industry standard.

 

For more information
Anki Malmborg Hager, CEO
SenzaGen AB
Email: anki.malmborg.hager@senzagen.com
Telephone: +46 768 284822

 

Thank you for a great Society of Toxicology and ToxExpo 2018!

We would like to extend a great thank you to all customers, partners, friends and collaborators for a great SOT and ToxExpo 2018! We had record numbers both in the audience for the presentation, at the poster presentation on validation for OECD and at the booth. We are very happy and proud to see the […]

We would like to extend a great thank you to all customers, partners, friends and collaborators for a great SOT and ToxExpo 2018!

We had record numbers both in the audience for the presentation, at the poster presentation on validation for OECD and at the booth. We are very happy and proud to see the rapidly growing interest for SenzaGen and our GARD products and wish to thank you all for your shown interest!

A webinar with the presentation from SOT will be held for those interested on Tuesday March 27 at 11:30 am.

Presentation pdf available here

Poster on validation available here

Register for webinar here.
The presentation will be held in English

Thank you and we look forward to future collaborations!

 

For more information:
Anki Malmborg Hager, CEO
SenzaGen AB
Email: anki.malmborg.hager@senzagen.com
Telephone: +46 768 284822

 

 

 

 

The Validation of GARDskin

Johansson A, Agemark M, Gradin R, Larne O, Appelgren H, Forreryd A, Jerre A, Edwards A, Hoepflinger V, Burleson F, Gehrke H, Roggen E, Johansson H SenzaGen, Lund, Sweden, Burleson Research Technologies, Morrisville, US, Eurofins, Munich, Germany Introduction The prevalence of allergic contact dermatitis (ACD) is estimated to >20% in the western world. Not only […]

Johansson A, Agemark M, Gradin R, Larne O, Appelgren H, Forreryd A, Jerre A, Edwards A, Hoepflinger V, Burleson F, Gehrke H, Roggen E, Johansson H
SenzaGen, Lund, Sweden, Burleson Research Technologies, Morrisville, US, Eurofins, Munich, Germany

Introduction
The prevalence of allergic contact dermatitis (ACD) is estimated to >20% in the western world. Not only the individual is affected, but downstream socioeconomic effects are high. To minimize exposure, chemicals must be safety tested. Traditional testing strategies like the murine local lymph node assay (LLNA) comprise animals, but the regulatory authorities, public opinion and economic interests require animal-free models. The Genomic Allergen Rapid Detection skin (GARDskin) is an in vitro assay addressing this need. Here, we present the results of the GARDskin ring trial (OECD TGP 4.106) for validity of the assay.

Conclusions
Transfer study
Transferability: 100%

Validation study
Reproducibility:
WLR: 82 – 89%BLR: 92% (92 – 100%)

Test performance
Accuracy: 94%Sensitivity: 93%Specificity: 96%

A blinded ring trial was performed to assess the functionality of the GARDskin assay. The data demonstrates that GARDskin is a powerful tool for assessment of chemical skin sensitizers, with a predictive accuracy of 94% and excellent reproducibility between laboratories.

Poster

Conclusive data on predictive performance of GARD™ in highly regarded scientific journal

SenzaGen announces today that research on the conformal prediction of the GARD™ assay has been published in the distinguished peer reviewed journal Toxicology in Vitro. The research presented in the publication proves that, as the first in vitro model for prediction of the skin sensitizing potential of chemicals, GARD™ is now capable of providing a […]

SenzaGen announces today that research on the conformal prediction of the GARD™ assay has been published in the distinguished peer reviewed journal Toxicology in Vitro. The research presented in the publication proves that, as the first in vitro model for prediction of the skin sensitizing potential of chemicals, GARD™ is now capable of providing a statistically valid measure of uncertainty for each individual prediction, thus allowing for classification of skin sensitizers with confidence. Consequently, GARD™ can meet the growing needs of high safety skin sensitization testing and particularly since there is now proof that all chemical reactivity domains, as well as pre- and pro-haptens are within GARD’s applicability domain. 

In the publication, Predicting skin sensitizers with confidence — Using conformal prediction to determine applicability domain of GARD™, a research group from Lund University, Swetox and SenzaGen reports its successful work on implementing a mathematical framework based on conformal prediction into GARD™ for the purpose of defining the applicability domain of the assay, something often neglected by test developers. Investigation of historical data within the framework demonstrates that all hitherto tested chemical reactivity domains, as well as pre- and pro-haptens are within the applicability domain of GARD, and can be predicted with a high degree of confidence. The results of this research demonstrate that the multivariate genomic biomarker signature, the unique technology of GARD makes it applicable across various chemical reactivity domains.

The mathematical framework in this implementation defines the applicability domain in terms of similarity to the samples used for model development and is capable of providing a statistically valid measure of uncertainty associated with each prediction. Furthermore, it also delivers a warning if a specific test sample is outside the region where the model is capable of generating a reliable prediction. Similar to the field of QSAR modelling, this information should be a minimal requirement for a successful validation also of in vitro models.

As the first in vitro model for prediction of skin sensitizing potential of chemicals, GARD™ is now capable of providing a statistically valid measure of uncertainty for each individual prediction, thus allowing for classification of skin sensitizers with even higher confidence. These scientific findings will benefit the chemical industry by providing better guidance of what test to use for different substances in different chemical domains and demonstrates the even broader applicability of GARD.

Full article:  Predicting skin sensitizers with confidence — Using conformal prediction to determine applicability domain of GARD Forreryd A., Norinder U., Lindberg T., Lindstedt M.  
https://www.sciencedirect.com/science/article/pii/S0887233318300237?via%3Dihub


For more information:
Anki Malmborg Hager, CEO, SenzaGen AB
Email: anki.malmborg.hager@senzagen.com
Telephone: +46 768 284822

 

About GARD™
GARD is a group of tests for assessing chemical skin sensitizers. The tests make use of genetic biomarkers for more than 200 genes which cover the entire immune reaction and are relevant to predicting the risk of hypersensitivity. The tests have over 90% reliability. This compares with the current predominant test method, experiments on mice, which has an accuracy of 70-75%. SenzaGen’s tests are also capable of measuring the potency of a substance’s allergenic properties. Consequently, GARD tests provide a much more comprehensive basis for determining whether a substance should be classified as an allergen than current testing methods.

About SenzaGen
SenzaGen makes it possible to replace animal experiments with in vitro genetic testing to determine the allergenicity of the chemicals we come into contact with in our daily lives, such as for example in cosmetics, pharmaceuticals, food products and dyes. The company’s patented tests are the most reliable on the market and provide more information than traditional evaluation methods. We ourselves sell the tests in Sweden and the USA, and we sell through partners in several other countries. Over the next few years the company will expand geographically, make alliances with more distribution partners and launch further unique tests. SenzaGen has its headquarters in Lund in Sweden and a subsidiary in San Francisco, USA. For more information visit www.senzagen.com

News post as pdf

Vatorpodden – Intervju med VD Anki Malmborg Hager

I detta avsnitt av Vatorpodden berättar Anki Malmborg Hager om den slutgiltiga valideringsrapporten av GARDskin som lämnats in till regulatoriska myndigheter samt rapporten om testets överlägsna noggrannhet jämfört mot dagens testmetoder. Anki talar även om teknologiplattformen GARDs övriga tillämpningsområden och bolagets viktigaste kommande milestones.

I detta avsnitt av Vatorpodden berättar Anki Malmborg Hager om den slutgiltiga valideringsrapporten av GARDskin som lämnats in till regulatoriska myndigheter samt rapporten om testets överlägsna noggrannhet jämfört mot dagens testmetoder. Anki talar även om teknologiplattformen GARDs övriga tillämpningsområden och bolagets viktigaste kommande milestones.

New colleague at senzaGen

Welcome Andy Forreryd Andy has started his position as Scientist with us here at SenzaGen after defending his doctoral thesis GARD – Genomic Allergen Rapid Detection, From Biomarker Discovery towards a State-of-the-art Testing Platform for Chemical Sensitizers at the Department of Immunotechnology, Lund University. Andy strengthens SenzaGen’s scientific team with his genuine expertise on the […]

Welcome Andy Forreryd

Andy has started his position as Scientist with us here at SenzaGen after defending his doctoral thesis GARD – Genomic Allergen Rapid Detection, From Biomarker Discovery towards a State-of-the-art Testing Platform for Chemical Sensitizers at the Department of Immunotechnology, Lund University.

Andy strengthens SenzaGen’s scientific team with his genuine expertise on the GARD platform, which formed the basis for his thesis. Andy is a specialist in biomarker discovery and statistical analysis of multivariate genomic data and has long experience in both cell culturing and in various technologies for gene expression measurements. He also has great experience in communicating research to both a scientific and public audience.

As The faculty opponent of the doctoral thesis, Dr Gavin Maxwell, stated when starting his opposition: “The thesis in one of the most complete analyses in the field”. We can only agree.

We are very happy to have you in our team, Andy!

 

Link to thesis

GARD – Genomic Allergen Rapid Detection, From Biomarker Discovery towards a State-of-the-art Testing Platform for Chemical Sensitizers at the Department of Immunotechnology, Lund University.