AXLR8 launched with €500K FP7 funding to replace animal tests

Image courtesy NIEHS

The project, AXLR8, which gets off the ground this week with €500,000 funding from the EU’s Framework Programme 7, is a collaboration between the animal protection body Humane Society International, and scientists at the Flemish Institute of Technology in Belgium and the Free University of Berlin in Germany.

AXLR8 is being billed as the start of the toxicology equivalent of the Human Genome Project, in which all toxicity pathways in the body are to be mapped. As critical pathways are identified, human cell-based assays will be developed to study chemical interactions at cellular and molecular targets within each pathway.

The funding will allow the researchers to pull together existing research that is relevant to this ambition and to set out a map for further research, whilst providing international coordination to ensure work is not duplicated. AXLR8 will also work to have the results adopted by the regulators and integrated into their approvals process.

The vision is that in future most toxicity testing will be carried out using a combination of computer modelling and human cell tests. These will be performed with unparalleled efficiency using high throughput systems capable of working nearly 1,500-times faster than a human technician.

Troy Seidle, Director of Research & Toxicology at Humane Society International says exposing relatively short-lived animals to unrealistic doses of chemicals in sterile laboratory conditions is a primitive approach to assessing chemical effects on humans in real-life conditions. “If utilised to their full potential, cutting-edge cell- and computer-based methods could transform toxicity testing, making it quicker, cheaper and more applicable to real-life human exposure scenarios. As well as having enormous benefits for human health and environmental protection, this transition towards 21st century toxicity could significantly reduce and ultimately replace testing on animals.”  

According to Seidle, there is considerable momentum behind the aim of a global transition to more modern and humane approaches in toxicity testing. This has been building up following the publication in 2007 the US National Research Council report “Toxicity Testing in the 21st Century: a Vision and a Strategy,” which called for an overhaul of safety testing.

Following this, US regulatory and research agencies joined forces under the banner of the “Tox21” initiative to research cellular mechanisms by which chemical toxicity occurs, and develop more predictive methods for safety testing.

Animal toxicity data are used to evaluate chemicals used in everything from cosmetics and household cleaners to pharmaceuticals, food additives, and pesticides. However, scientists and legislators across the EU and US recognise that conventional tests, in which animals such as rodents, rabbits and dogs are given unrealistically large doses of chemicals, are not only costly and time-consuming, but of uncertain relevance to human health.

A recent report by the US Food & Drug Administration estimated that new drug candidates have only an 8 per cent chance of reaching the market, in large part because animal studies so often, “fail to predict the specific safety problem that ultimately halts development.”

So for example, evaluating the cancer-causing potential of a single chemical in a conventional rodent test takes up to 5 years, 800 animals and costs €3 million. For the same price and without any use of animals, as many as 350 chemicals could be tested in less than one week in 200 different cell or gene tests using a robot-automated high throughput approach.

This mechanistic approach involves a virtual dissection of the human body into its various cell types (brain, skin, lung, liver, and so on) and then tests each of these cell types individually for different types of toxic response.

Computerised systems biology and pharmacokinetic models are then used to recreate the whole body.

Humane Society International says mapping the toxic pathways of the human body is an ambitious project that could take between ten and twenty years – toxicology’s equivalent of mapping the human genome. Such a project will require international collaboration and substantial investment.

The European Union has put considerable effort into the development and regulatory uptake of animal replacement, reduction and refinement (3Rs) approaches in toxicity testing, investing over €200 million to develop tests. Some EU-pioneered tests have been accepted internationally. Funding from the 6th and 7th Framework Programmes is currently supporting 18 large-scale integrated projects to develop non-animal methods and strategies for reproductive toxicity and carcinogenicity, skin allergy and other health and environmental risks.