January 26, 2016

expert reaction to alternative for animals during toxicity testing

Studies which assess the toxicology of new drugs typically have some element of animal testing, and a paper published in the journal Nature Communications has described a method using in vitro tests which are carried out without animals. The authors report that these tests were better than animal models at predicting toxicity of drugs to humans.

All our previous output on this subject can be seen here. The SMC also produced a Factsheet and a Briefing Note on animal research.

Prof. Andy Smith, Senior Scientist at the MRC Toxicology Unit, University of Leicester, said:

“The paper by Huang et al details impressive comparative work that has been known to be ongoing as collaborations between US public institutions.

“The results are a demonstration of how careful systematic multi in vitro toxicity endpoints and large, wide ranging examples of candidate chemicals at more than one exposure level, can be used to screen and predict for potential human toxicity. As the authors describe this could greatly aid in prioritisation of chemicals, especially in the developments of drugs, for further in-depth testing and understanding mechanisms of toxicity.

“These processes will still need in vivo toxicity investigations as will data for risk assessment exercises for food and environmental exposure. Probably the greatest gains will be in decreased costs and time in streamlining and prioritizing processes for drug development.”

Prof. Jan Schnupp, Professor of Neuroscience, University of Oxford, said:

“Assuming the methodology is as sound as it appears, these developments are no doubt excellent news because they will allow substantial reductions in the number of toxicity tests on animals. But it is unrealistic to hope that they will lead to a complete replacement of all animal toxicity testing in the near future, because our bodies are very complex and contain many more different cell types and metabolic pathways than can so far be included in cell cultures in test tubes.

“Substances that do not pass the test-tube and computer tests described in the paper can be declared unsafe without a need for animal testing, and a substance that passes the test is ‘probably safe’, but you can’t be 100% certain because there is still a small chance that it might interfere with processes in your body that aren’t replicated in the test-tube tests. To get greater certainty, some animal testing may therefore still be needed, but the numbers should certainly decline as many toxins can be identified without animal tests, and the chances that animals undergoing tests on pre-screened substances will have to suffer any toxic effects should also be pretty small. Both numbers and severity of animal tests can thus be greatly reduced. So this is no doubt a very encouraging development.”

Prof. Sir Colin Berry, Emeritus Professor of Pathology at Queen Mary University of London, said:

“This robust piece of research suggests a way forward in using alternatives to animal testing in regulatory toxicology.

“There are clear deficiencies in the current methodology which I have raised before in a critical letter published in Nature about waste of animals in testing and, more recently, a critique of the International Agency for Research on Cancer (IARC) process in Toxicology Research.

“Any system that looks to improve things is welcome, but it is important to know that there will be a long route to validation of this methodology. In the shorter term, at least, it may help scientists to better design studies. Whilst the current pattern of testing must continue for the foreseeable future, this research could help to improve the design of current tests.

“Changing things is difficult; nobody liked the Draize test (an acute toxicity test where substances were applied to the eyes of rabbits before being rinsed out and recording the effects) but it took 18 years to get it out of the testing programme. Many internationally agreed protocols would need to be altered for the findings from this research to be put in place.”

Dr Vicky Robinson, Chief Executive, National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), said:

“The findings of this study are a positive step towards the use of cell-based approaches to predict the health effects of chemicals.

“The increased human relevance of the approaches compared with existing animal data supports the long-term goal of reducing reliance on animal toxicity testing.

“Further work examining additional types of toxicity and building awareness with the relevant regulatory agencies will be key before these types of approaches can be applied in routine practice in future.”

‘Modelling the Tox21 10 K chemical profiles for in vivo toxicity prediction and mechanism characterization’ by Huang et al. published in Nature Communications on Tuesday 26^th January. 

Declared interests

Prof. Smith: Expert external member for European Food Safety Authority and member of UK Expert Committee on Pesticides

Prof. Schnupp: “I have no competing interests to declare”

Prof. Berry: “I used to Chair the Pesticide Safety Committee, the Committee on Dental and Surgical Materials and served on the CSM.  Since retirement I have consulted for Monsanto, Syngenta and Johnson and Johnson and occasionally for other pharmaceutical companies and given medico-legal advice about various chemicals to multiple sources, including the Courts.”

Dr Robinson: “I have no conflicts.”