alternatives organs on a chip the wyss institute for biologically inspired engineering (us) intends to develop in-vitro organs for drug screening and thereby eliminate the use of animals for this type of testing. one model is the "lung-on-a-chip". this combines microfabrication techniques with modern tissue engineering and mimics the complicated mechanical and biochemical behaviours of a human lung. human toxome toxicity testing typically involves studying adverse health outcomes in animals subjected to high doses of toxicants with subsequent extrapolation to expected human responses at lower doses. the system relies on the use of a 40+year-old patchwork of animal tests that are expensive (costing more than $3b per year), time-consuming, low-throughput and often provide results of limited predictive value for human health effects. the low-throughput of current toxicity testing approaches (which are largely the same for industrial chemicals, pesticides and drugs) has led to a backlog of more than 80,000 chemicals to which humans are potentially exposed whose potential toxicity remains largely unknown. in 2007, the national research council (nrc) released the report "toxicity testing in the 21st century: a vision and a strategy", that charted a long-range strategic plan for transforming toxicity testing. the major components of the plan include the use of predictive, high-throughput cell-based assays (of human origin) to evaluate perturbations in key toxicity pathways, and to conduct targeted testing against those pathways. this approach will greatly accelerate our ability to test the vast "storehouses" of chemical compounds using a rational, risk-based approach to chemical prioritization, and provide test results that are hopefully far more predictive of human toxicity than current methods. although a number of toxicity pathways have already been identified, most are only partially known and no common annotation exists. mapping the entirety of these pathways (i.e. the human toxome) will be a large-scale effort, perhaps on the order of the human genome project. research initiatives seurat-1 seurat-1 is a long-term strategic target for "safety evaluation ultimately replacing animal testing". it is called "seurat-1" to indicate that more steps have to be taken before the final goal will be reached. seurat-1 will develop knowledge and technology building blocks required for the development of solutions for the replacement of current repeated dose systemic toxicity testing in vivo used for the assessment of human safety. seurat-1 is composed of six research projects, which started on january 1, 2011 and will run for five years. these projects will closely cooperate with a common goal and combine the research efforts of over 70 european universities, public research institutes and companies. the collaboration between these six research projects, the dissemination of results, the cooperation with other international research teams, and the continuous updating on research priorities will be facilitated by the coordination and support action project "coach". seurat-1 was developed through the framework programme 7 (fp7) research initiative and was created through a call for proposals by the european commission (ec) that was published in june 2009. the cosmetics europe industry offered to match the ec's funds to make a total of eur 50 million available to try to fill current gaps in scientific knowledge and accelerate the development of non-animal test methods. euroecotox laboratory animals are not restricted to rats, mice, dogs, and rabbits, but also include fish, frogs and birds. research into alternatives to replace these species is often neglected, although fish are the third most widely used laboratory animal used for scientific purposes in the eu. this is also the field where until now only two alternative tests exist worldwide: one guideline, oecd tg 236, and one guidance (oecd series on testing and assessment 126) are so far available. euroecotox is a european network for alternative testing strategies in ecotoxicology. it was funded by the seventh framework programme (fp7) of the european commission environment programme. the main objectives of the euroecotox network are: to contribute to the advancement of alternative methods of ecotoxicity testing in europe. to promote the validation and regulatory acceptance of new alternative ecotoxicity methods. to facilitate the networking of research groups working in the field of alternative ecotoxicology. to provide a gathering point for all stakeholders involved in the development, validation, regulatory acceptance and final use of alternative ecotoxicity testing strategies. to act as the one voice for alternative ecotoxicity testing in europe. axlr8 axlr8 is a coordination action funded by the european commission directorate general for research & innovation under the 7 framework programme 7 (fp7) health theme. the european commission is currently funding a number of research consortia to develop new 3rs (replacement, reduction and refinement) test methods and strategies as potential alternatives to the use of animals in safety testing. monitoring of these 3rs activities at pan-european, national, and international levels is vital to facilitate swift progress. axlr8 aims to fulfil this growing need by providing a focal point for dialogue and collaboration. humane society international is part of the consortium. regulation eu directive 2010/63/eu on january 1, 2013, eu directive 2010/63/eu "on the protection of animals used for scientific purposes" entered into force for the eu member states (ms), repealing directive 86/609/eec. because it is a directive, it allows member states certain flexibility in transposition of national rules. the status of the implementation of the new directive in the eu is described by the ec general environment directorate. article 1.3: the new eu directive applies to the following animals: (a) live non-human vertebrate animals, including: (i) independently feeding larval forms; and (ii) foetal forms of mammals from the last third of their normal development; (b) live cephalopods. article 4: the directive refers directly to the 3rs: "principle of replacement, reduction and refinement". article 47-2: member states shall assist the commission in identifying and nominating suitable specialised and qualified laboratories to carry out such validation studies. in july 2013, the commission announced the creation of netval (european union network of laboratories for the validation of alternative methods). eu-netval's primary role is to provide support for eurl ecvam validation projects, including aspects of training and dissemination, and the identification of methods that have a potential to reduce, refine or replace animals used for scientific purposes. currently there are thirteen test facilities in nine member states: germany (3), the netherlands (2), spain (2), belgium (1), czech republic (1), finland (1), france (1), italy (1) and sweden (1). other regulations the cosmetics directive provides the regulatory framework for the phasing out of animal testing for cosmetics purposes. it establishes prohibitions against (a) testing finished cosmetic products and cosmetic ingredients on animals (testing ban), and (b) marketing in the eu finished cosmetic products and ingredients included in cosmetic products which were tested on animals for cosmetics purposes (marketing ban). the same provisions are contained in cosmetics regulation eu 1223/2009, which replaces the cosmetics directive as of july 11, 2013. in 2007, eu legislation on the registration, evaluation, authorisation and restriction of chemicals (reach ec 1907/2006) came into force, relating to chemicals and their safe use. the aim of reach is to improve the protection of human health and the environment through the better and earlier identification of the intrinsic properties of chemical substances. it promotes the use of alternative methods for animal testing, but does not oblige the test performer to do so; "article 25.1 - in order to avoid animal testing, testing on vertebrate animals for the purposes of this regulation shall be undertaken only as a last resort. it is also necessary to take measures limiting duplication of other tests." in parallel to the adoption of reach, the ec published standardised and accepted methods for testing hazardous properties of chemicals. these were written into the "test methods regulation". all the alternative test methods among the in vivo studies are included in part b; "the european union is committed to promoting the development and validation of alternative techniques which can provide the same level of information as current animal tests, but which use fewer animals, cause less suffering or avoid the use of animals completely. such methods, as they become available, must be considered wherever possible for hazard characterisation and consequent classification and labeling for intrinsic hazards and chemical safety assessment." eu philosophy on food additives, food enzymes, and food flavourings and ingredients intended for human consumption is that none should be put on the market unless they are included on a published community list of authorised substances, in accordance with the conditions laid down in relevant food law. this approach is intended to bring food producers into compliance with the provisions of regulation (ec) 1334/2008 that pertain to the safety of food flavourings. as part of the approval process, the ec will require full disclosure of study data, safety issues, and toxicological findings for all such additives. within the eu animal welfare law (2010/63/eu), the principles of the 3rs are invoked whenever toxicological test methods are necessary. organizations and programs scientific congresses the european society for alternatives to animal testing (eusaat) organises an annual conference in linz (austria) for dissemination and validation of alternative methods to animal testing promotion of research in the field of the 3rs reduction of the use of animals for tests in the field of education and continuing education reduction of suffering and stress of laboratory animals by better breeding, keeping, test planning and other accompanying measures experts' guidance and referees' opinion for public and private organizations, companies, universities suitable information for the public and the media the world congress on alternatives and animal use in the life sciences takes place every three years. the next conference (10th) will be held in september 2017 in seattle. the 1st latino-americano congress on alternative to animal testing took place in 2012. colama (i congresso latino-americano de metodos alternativos ao uso de animais no ensino, pesquisa e industria). the johns hopkins university center for alternatives to animal testing (caat) co-organizes an annual symposium on the 3rs with the usda's animal welfare information center (awic) and nih's office of laboratory animal welfare. previously known as the social housing symposium, the symposium has occurred annually (except for 2015) since 2013 with past symposia archived on video on the awic website. videos of the most recent symposium, "7th annual 3rs symposium: practical solutions and success stories", held in june 2020, may also be found on the awic website. industry and corporate initiatives cosmetics europe: represents the interests of more than 4000 companies in the cosmetic, toiletry and perfumery industry since 1962. unilever: "we do not test finished products on animals unless demanded by the regulatory authorities in the few countries where this is the law. in such cases, we try to convince the local authorities to change the law. where some testing of ingredients is required by law or currently unavoidable, we aim to minimise the number of animals used." basf: "systematic screening investigations provide information about important toxicological properties of substances at an early stage of development. ... we replace animal experiments whenever an alternative method is available that complies with an oecd test guideline and is recognized by the authorities." animal welfare and animal rights organizations eurogroup for animals: "an estimated 12.1 million animals – including dogs, rabbits and even our closest genetic relatives, primates – are used in laboratory research throughout europe every year. eurogroup focusses on ensuring their protection and works with legislators, experts and industry with the aim of ultimately replacing all animal experiments with viable alternatives. we continue to actively promote the replacement, reduction and refinement of animal tests and do all we can to improve the lives of those animals currently used for research." vier pfoten (four paws) (austria) antidote (france) "when it is about assessing drug safety, humans are not 70kg rats! it is about time to move on from the actual paradigm on assessing drug safety. the first step would be to eliminate all the regulatory requirements for animal testing and replace these tests by 21st century methods." deutscher tierschutzbund (germany) lega anti vivisezione (italy) the alexandra association (monaco): "... aims at stimulating research and development (r&d) in the area of alternative methods to animal experimentation by providing political, technical and educational support to researchers and entrepreneurs worldwide. in particular alternative methods based on 'open source' concepts i.e. non-patent protected core technologies for human tissue reconstruction and cell culture technologies will be actively promoted." british union for the abolition of vivisection (buav): "for over