398 A Menache (AltTox 2008) Since the overall procedure of validation, peer review and regulatory acceptance can take up to seven years on average to complete, it is perhaps unsurprising that companies are not enthusiastic to embark on such projects and prefer to rely on animal data (Center for Alternatives to Animal Testing 2009) This sad situation is also counterproductive for innovative projects that could accelerate the replacement of animal use, since a state-ofthe-art test method submitted for validation today may find itself already out of date when it finally becomes available after a period of seven long years (Bottini 2007) Fundamental Research Fundamental (or basic) research is defined by the OECD (1963) as: Experimental or theoretical work undertaken primarily to acquire new knowledge of phenomena and observable facts, without any particular application or use in view; It is usually undertaken by scientists who may set their own agenda and to a large extent organise their own work Although fundamental research is primarily curiosity driven, researchers will justify their use of animals by claiming some possible benefit for human health (Greek and Greek 2010) Indeed, most fundamental research involving animals would not receive funding otherwise, as most EU citizens (68 %) are opposed to the use of animals in curiosity driven research, according to the largest EC survey of its kind published in 2006 (Citizen’s questionnaire on the revision of Directive 86/609/EEC on the protection of animals used for experimental and other scientific purposes—Question 22) Fundamental research is de facto almost immune to the principle of ‘replacement’ (within the context of the 3Rs principle of ‘replacement, reduction and refinement’) embodied in Directive 2010/63/EU Unlike regulatory toxicology, where there are usually clearly defined end points, fundamental research is hypothesis-driven, where the researcher may or may not obtain a result Whereas animal use is still a legal requirement in the pharmaceutical and the chemical industry, there is no legal obligation to use animals in fundamental research Provided that a researcher can justify the animal study within the context of the 3Rs and obtain the necessary funding, there is very little scope for replacement of animals in fundamental research as will be explained Following are a few examples to illustrate this point