15 June, 2017

Do you know your QSARs from your SPECT?

By Stefan Pudenz

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As the drive to reduce, refine and replace animal testing continues, the array of non-animal technologies (NATs) is increasing. But do you know your QSAR from your SPECT? And will either be accepted by regulators? Read on to find answers.

What's driving the rise of non-animal testing?Clouds and numbers

Regulators worldwide now require chemical companies to use acceptable non-animal test methods and to only use animals as a last resort. But it’s not just regulation that’s driving the use of NATs; other factors are at play too – new technological innovations, global politics, societal pressures to protect animals, and the need to enhance efficiency and reduce costs in early screening of new molecules are all driving NAT development. 

How is non-animal testing regulated?

In Europe, under REACH (Regulation, Evaluation, Authorization and Restriction of Chemicals) regulation, animal testing must be used only as a last resort. However, before you can use an alternative test, it must be validated and gain regulatory acceptance. The European Centre for the Validation of Alternative Methods (ECVAM) is responsible for validation, while regulatory acceptance is facilitated through the European Commission’s “preliminary analysis of regulatory relevance” (PARERE).

Check out the European Chemicals Agency (ECHA)’s practical guide on alternatives to animal testing for more help on ways to avoid animal testing.

In the USA, the Interagency Committee on the Validation of Alternative Methods (ICCVAM) is responsible for reviewing and validating test methods and producing guidelines and regulations on alternative toxicological tests. The Environmental Protection Agency (EPA)’s Office of Pesticide Programs (OPP) is developing and evaluating NATs, and is also driving the use of integrated approaches to testing and assessment (IATAs). The ToxCast program is one of the successful EPA initiatives, it aims to speed up screening using high throughput screening methods and computational approaches to rank and prioritize chemicals.

In the rest of the world, the acceptance of NATs is increasing. For example, in Japan, some Organization for Economic Co-operation and Development (OECD) toxicity tests are currently accepted and in China, South Korea and Brazil, NATs are generally accepted for the safety assessment of adult cosmetics.

Common types of non-animal tests

  • In vitro testing uses cells or tissue samples in laboratory-based studies looking at cellular toxicity
  • Microfluidic 3D organ culture replicates the cellular pathways found in the body. Organ-like tissue systems are created in the laboratory, which can provide more complex information than in vitro tests
  • Microdosing involves the administration of tiny amounts of substance to human volunteers. The level of substance is high enough to cause cellular effects, but too low to affect the entire body
  • Imaging studies: non-invasive imaging techniques can be used to observe the effect of a substance on body systems. Tests include magnetic resonance imaging (MRI), positron emission tomography (PET) and single-photon emission computed tomography (SPECT)
  • Computer models and simulations: many computer-based approaches can predict and simulate substance effects on the body through virtual human organs or metabolism programs. Quantitative structural-activity relationships (QSARs) are theoretical models used to predict the physicochemical, biological and environmental properties of compounds based on their chemical structure

 Check out our e-book for more information on NATs and their uses

The importance of an integrated approach

Skin sensitization is a big area of concern when looking at substance toxicity. Although non-animal tests exist to address some aspects of this toxicity, there is no integrated approach that could replace current animal models. However, this may be set to change, as in April, the Working Group of the National Coordinators for the Test Guidelines Programme (WNT) at the OECD kicked-off a project developing a new type of test guideline (TG). The new TG would provide ‘defined approaches’ to in vitro skin sensitization, describing how multiple, non-animal tests could be used together as a testing strategy. This new project is proposed as part of the OECD IATA program.

IATA recognizes that in many cases the biology is too complex to allow direct, one-for-one replacement of animal models with NATs. So IATAs combine multiple data sources from in vitro, in chemico, in silico and physicochemical testing. For an update on test guidelines click here.

In our new e-book, we pinpoint the main issues and offer key learnings when it comes to QSARs;Quantitative structural-activity relationships (QSAR) ebook download now


About the Author

Stefan is expert consultant at Envigo Ltd. and technical lead for in silico modeling and statistics. He holds a Dr-Ing in Environmental Science and Technology and has more than 25 years of experience in quantitative methods concerning the exposure, fate and hazard of chemicals, including modeling, statistics, and QSARs.

Throughout his career, he has successfully implemented innovative solutions for analyzing (eco-)toxicological and environmental data for a number of key customers, being recognized as qualified expert in all aspects of environmental modeling and statistics. Stefan has developed software for contaminant transport modeling, multivariate analysis, trend analysis, prioritization, ranking and decision aid, and implemented several customized solutions at various customers. Furthermore, a publication record of more than 60 papers on multivariate approaches and modeling in environmental sciences underpins his scientific competencies.

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Category // Chemical, non-animal technologies, QSAR, Stefan Pudenz