In the spotlight: newly published book, ‘Reducing, Refining, and Replacing the Use of Animals in Toxicity Testing’

Published in 2014, Reducing, Refining, and Replacing the Use of Animals in Toxicity Testing explores the exciting advances, as well as the hurdles, encountered in the development of alternative methods for toxicity testing. 

The book was coedited by Dr David Allen, from Integrated Laboratory Systems in North Carolina. Dr Allen has many years of experience in evaluating alternative toxicology methods. Here he tells the NC3Rs about his involvement in editing the book and gives us a brief insight into its contents.


Regulatory safety testing is performed to assess the potential hazards presented by substances such as industrial chemicals, consumer products, and pharmaceuticals, so that they can be properly labelled and appropriate precautions taken.  Historically, many regulatory test methods have been based on laboratory animal tests. However, new legislation, the need to test thousands of chemicals, and a shift towards collecting more mechanistic information relevant to human health effects have contributed to a shift towards incorporating non-animal approaches into regulatory safety testing. The past several years have seen the development of a number of non-animal testing methods and approaches for identifying potential hazards.

New methods must perform as well as currently accepted methods in order to maintain protection of public health and the environment. Therefore, test method validation is necessary in order to demonstrate that an alternative is both scientifically valid and provides adequate protection relative to currently accepted methods. But traditional approaches to validation, based on one method directly replacing another, may not fit the ever-evolving technologies being applied to test method development.

Technological advances have led to the successful development of alternatives for some toxicity endpoints required for regulatory testing, such as skin and eye corrosivity and irritation testing, which reduce of even eliminate the need for animals. Likewise, methods are available to address some of the multiple mechanisms associated with longer term and complex processes like carcinogenicity and reproductive and developmental toxicity. However, none can account for them all. To address this issue, integrated testing strategies are being developed to facilitate a broader assessment of these endpoints.

I’ve been a part of the process of developing, validating, and implementing alternatives for regulatory safety testing for more than a decade. This experience has given me the opportunity to develop collaborations and networks with internationally recognized scientists representing the regulatory, industrial, academic, and animal welfare sectors. I’m pleased that many have contributed their insights and knowledge to the book. Readers can expect an excellent historical perspective tracing back to the beginnings of the movement that was pioneered by William Russell and Rex Burch, along with detailed analyses of 3Rs trends in the toxicological literature and measures of the impact of 3Rs activity. After successive chapters describing the various regulatory testing requirements and the importance of international harmonization on test method implementation, the text describes the ever-expanding “toolbox” of test methods available to the toxicologist to determine the hazards associated with test materials of interest.

With the variety of cell-based, chemical and computational approaches in the pipeline, it is important to consider which methods are optimal and how they should they be used to best predict the human response? By combining in silicoin vitro, and ex vivo methods, coupled with state-of-the-art mid- and high throughput technologies that rely almost completely on biochemical- and cell-based in vitro assays, toxicologists are moving closer to using mechanistically based alternatives without requiring the use of live animals. I hope that readers of the book will enjoy learning about the many options, challenges and opportunities ahead for the continued transformation of the science of toxicology.

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