Introduction
ASAT brings together Assuring Safety and Animal Testing. Its aspiration is high: Assuring Safety without Animal Testing.

Since the late 50ies of the last century much time and energy has been invested in animal welfare. It was based on the principle of the 3Rs; refining, reducing and replacing. Applying the principle of the 3Rs as an objective for all animal testing has not made it easy to identify clear and achievable animal welfare targets.

Objective of testing
Animal testing is being carried out for a variety of very different reasons. A distinction has been made between animal testing for safety reasons i.e. health protection[1] and animal testing for other reasons such as science, R&D of fore example medicines, pesticides and quality control in vaccine production. This warp and woof approach enabled the identification of different objectives for different applications. The warp is the objective of the testing and the woof is a feasible target in terms of 3Rs based on available science and technology.

Once this distinction had been made ASAT became visible as a distinct and achievable objective for safety testing. Adverse effects from medicines that are associated with their mode of action could not be included in ASAT as far as its promise –without Animal Testing- is concerned.

Medicines
This caveat was based on the assumption that for the foreseeable future it would not be possible to do without animal testing[2] in the exploratory phases of R&D[3]. Therefore it would be unavoidable to have animal data available that have been generated in R&D that could and very likely will be used to manage the prevention of these side effects. A similar exclusion applies to R&D of rodenticides and safety issues relating to their mode of action. Safety of medicines and rodenticides associated with biological processes other than those that are responsible for the intended or therapeutic effect was expected to be manageable within the realm of ASAT

Warp and Woof
The warp and woof approach can also relate different categories of chemicals to the different objectives for animal experiments (figure). The chemicals have been stratified according their intended biological effect and the phylogenetic distance between this biology and man. Fore each box in the matrix an assessment has been made of the feasibility of achieving one or more of the 3Rs.

This makes visible where animal testing is currently applied and where it could become redundant in the future; green boxes[4]. ASAT has developed from a concept into a promise. In order to preserve the credibility of the ASAT® brand its scope has to be safety of chemicals except:
chemicals that have been designed to perturb human (mammalian) biology and
health risks caused by mechanism of action responsible for its intended effect.

This could easily give the false impression that ASAT has no relevance for R&D and mode of action related safety in medicines and rodenticides. The opposite happens to be the case. The challenge will be to establish co-operation and interaction whilst at the same time maintaining clarity as to what ASAT can stand for.

ABSRAT
The new risk paradigms, experimental models and application of technologies will change the nature and the number of animal tests in those areas where replacement does not seem achievable resulting reduction and refinement. Thus a second perspective could emerge: Assuring Benefit/Safety through Reduced Animal Testing, ABSRAT. Clinical medicine and medicines research in humans will be an important source of information in developing ASAT.

In the world of pharmaceuticals and pesticides there is no clear demarcation of the work on efficacy, its related safety and safety in general. However, there are a differences between the worlds of safety in medicines, pesticides, household cleaners, personal care, food and the safety of chemicals in water, air and other environmental compartments. Scientists working in each of these areas have limited interaction with scientists from other domains.

Synergy and Co-operation
Because ASAT is public health risk based there is a need for co-operation and interaction. For each chemical, application or product the same public health risks have to be assessed based on the same human biology. No common basis would result in an enormous waste of resources and time and could create the risk of different levels of health protection for different product categories or different geographies.

ASAT and ABSRAT are complementary domains. They have a strong synergy and combine a high level of ambition regarding animal welfare. In conjunction they will appeal to all scientists involved studying the interaction of the human biology and exogenous chemicals even though the nature of the chemicals and their application varies widely.

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[1] The same applies to the protection of the ‘biotic environment’.
[2] Animal testing is considered to be exposing vertebrates to chemicals to generate data for (human) health protection.
[3] Animal Testing for regulatory reasons is based on today’s practice and could be obsolete in the future depending on the rate of acceptance of safety delivered through an ASAT approach.
[4] A blank box stands for ‘no animal testing’.