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Example of an ECVAM Scientific Advisory Committee statement that endorses the use of an alternative method
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The roles played by the European Centre for the Validation of Alternative Methods (ECVAM) and its advisory committee, the ECVAM Scientific Advisory Committee (ESAC), in the evolution of alternative methods are described. Particular emphasis is given to the process by which ECVAM and the ESAC assess the scientific validities of alternative methods,...
Context in source publication
Context 1
... statements that endorse alternative methods are co-signed by the Chairman of the ESAC (the Head of ECVAM) and by the Head of the Chemical Substances Unit of DG ENV (referred to as DG ENV/C.3). An exam- ple of such a statement, referring to the use of the EPISKIN TM human skin equivalent for skin corrosivity testing, is reproduced in Figure 1. The full version of this statement has been published previously (22). ...
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Citations
... Several initiatives for establishing reliable resources have already been launched to stimulate the use of NAMs, to facilitate knowledge sharing on 3Rs (Replacement, Reduction, Refinement), and to bridge the gap between regulators and biomedical scientists. Some of these have been launched by the "European Commission" (EC), the responsible authority in this area in Europe (Worth and Balls, 2001), such as the "Inventory of the 3Rs knowledge sources" 1 and the "DataBase service on ALternative Methods" (DB-ALM) 2 . Other information resources include, amongst others, 1) the "ALTBIB," developed by the National Library of Medicine, as a tool for scientists who are looking for information on alternatives to animal testing 3 , 2) "AnimAlt-ZEBET," a database compiling methods linked to the 3Rs, published by the German Centre for the Protection of Laboratory Animals 4 , and 'Norecopa' a Norwegian platform to stimulate the 3Rs 5 . ...
By applying “New Approach Methodologies (NAMs)” based on innovative technologies such as computer modeling, high throughput testing, omics, and sophisticated cell cultures, the use of experimental animals in the life sciences can be reduced or sometimes even completely avoided. Stimulating NAMs may benefit from a bottom-up approach, i.e., local initiatives mapping the available NAMs and promoting their use. An example of such an initiative in Belgium is the RE-Place project, which collects the available NAMs in one central database, and links this knowledge with the names of experts and research centers. To this extent, a template was created to collect the information of interest in a fast and consistent manner. Based on this template, a web-based application was developed to facilitate the entry of information, which was evaluated in a pilot study by experts in the field of NAMs. After integration of their feedback, a revised version of the RE-Place online tool was launched to the public. Aspects such as user-friendliness, quality of submitted information, protection of personal data and Intellectual Property (IP) rights were all considered in the development process. Hurdles like incentives for collaboration were also taken into account. Information submitted with the online tool is directly integrated in the RE-Place open access database. By consulting the database, scientists from various disciplines can easily identify the different types of NAMs and the experts using them in Belgium. As such, the RE-Place database contributes to building trust in the use of NAMs and stimulating their use and regulatory uptake.
... After 20 s, the formulation was removed with saline solution. The CAM was observed under a magnifying glass for 5 min to determine the incidence of any irritant effects in the CAM blood vessels (hyperemia, hemorrhage or coagulation) (Luepke and Kemper, 1986;Worth and Balls, 2001;Liebsch and Spielman, 2002). The irritant effects were classified by scores (1, 3, 5, 7, or 9) according to the time they were observed: less than 30 s (hyperemia: 5; hemorrhage: 7; clot formation/opacity: 9); between 30 and 120 s (hyperemia: 3; hemorrhage: 5; clot formation/opacity: 7); or between 120 and 300 s (hyperemia: 1; hemorrhage: 3; clot formation/opacity: 5). ...
Chronic exposure to solar radiation could contribute to premature skin aging and skin cancer. Skin presents its own antioxidant defense, however when defenses are out of balance, reactive oxygen species could damage biological structures. In the present work, an oil-in-water photoprotective emulsion was developed and Bauhinia microstachya var. massambabensis Vaz, Fabaceae, extracts at 1% (obtained by extraction with different solvents) were added to this emulsion. In vitro and in vivo efficacy and safety of the formulations were evaluated. Spectrophotometric methods and in vivo Colipa test were performed to evaluated efficacy of the formulations, through sun protection factor (SPF) determination and UVA protection factor (UVA-PF) assessment. To the in vitro safety assessment HET-CAM, CAM-TBS and Red Blood Cell tests were performed. Results showed that both extracts contributed to a higher in vivo photoprotection (SPF 18) when compared to the formulation without extract (SPF 13), this result could be attributed to the antioxidant activity of the plant extracts that act by capturing reactive oxygen species. Concerning safety, all formulations were considered non-irritant according to in vitro tests. Formulations containing extracts could be considered efficient and safe for cosmetic use since they presented higher SPF and passed the toxicity tests.
... eSAC issues an eSAC statement on the validity of a new test method which then is communicated by the Chemical Substances Unit of the eC's environment DG to other Commission Services and to other organizations such as the eU Competent Authorities, OeCD, and ICCVAM. the Commission Services may accept and/or endorse an eSAC statement, suggest further study, or request clarification (Worth and Balls, 2001). Discussions with eU authorities who make the acceptance decision are coordinated by the Commission Services. ...
European Union (EU) legislation on the protection of animals used for scientific purposes requires that alternative methods must be used instead of animal tests wherever they are available. Unfortunately, this provision is not implemented to its full extent when it comes to risk assessment of chemicals and new products prior to their authorization and placing on the market in the EU. In this study, we screened data requirements of relevant EU law regarding chemicals (REACH), biocides, pesticides, and food safety (Novel Food) and found that data requirements as part of the risk assessment do not always reflect state-of-the-art science and technology. Most of the data requirements we investigated still include testing on animals for many toxicological endpoints, even though more than 40 alternative testing methods accepted at the level of the EU or the OECD are available. This may be due to a multitude of reasons, including a shortage of both manpower to implement existing knowledge and expertise in the field of alternative methods, as well as unclear and misleading statements on the applicability and state of validation of alternative methods. In conclusion, we strongly suggest a homogeneous EU-wide approach for all areas involving risk assessment of substances with the goal of better implementing the 3Rs and complying with Directive 2010/63/EU. This also would streamline data requirements, save costs on various levels, and enhance product safety for consumers.
... In 1995, in cooperation with international experts and based on the experience gained in validation studies, ECVAM established a formal process for the prospective validation of alternative methods (116,117). An alternative method can be thought of as a combination of a test system and a prediction model (118,119), where the prediction model is an algorithm which converts the data generated with the in vitro test system into a prediction of a toxicological endpoint in animals or humans. Both are independently assessed during a validation study. ...
... Validation of alternative tests is the process by which the reliability and the relevance of a test are established for a particular purpose. In collaboration with experts, ECVAM has established guidelines on the validation of alternative toxicological methods, which are applicable to the testing of industrial chemicals, pharmaceuticals, food ingredients and biologicals Curren et al., 1995;Worth and Balls, 2001). The validation process used at ECVAM has proven to be successful and has led to the regulatory acceptance of several alternative tests (Spielmann and Liebsch, 2002). ...
Detection and characterisation of chemical-induced toxic effects in the central and peripheral nervous system represent a major challenge for employing newly developed technologies in the field of neurotoxicology. Precise cellular predictive test batteries for chemical-induced neurotoxicity are increasingly important for regulatory decision making, but also the most efficient way to keep costs and time of testing within a reasonable margin. Current in vivo test methods are based on behavioural and sensory perturbations coupled with routine histopathological investigations. In spite of the empirical usefulness of these tests, they are not always sensitive enough and often, they do not provide information that facilitates a detailed understanding of potential mechanisms of toxicity, thus enabling predictions. In general, such in vivo tests are unsuitable for screening large number of agents. One way to meet the need for more powerful and comprehensive tests via an extended scientific basis is to study neurotoxicity in specific cell types of the brain and to derive generalised mechanisms of action of the toxicants from such series of experiments. Additionally, toxicokinetic models are to be developed in order to give a rough account for the whole absorption, distribution, metabolism, excretion (ADME) process including the blood-brain barrier (BBB). Therefore, an intensive search for the development of alternative methods using animal and human-based in vitro and in silico models for neurotoxic hazard assessment is appropriate. In particular, neurotoxicology represents one of the major challenges to the development of in vitro systems, as it has to account also for heterogeneous cell interactions of the brain which require new biochemical, biotechnological and electrophysiological profiling methods for reliable alternative ways with a high throughput.
... ICCVAM/OECD criteria and principles for validation and acceptance evolved and became the basis for practical validation studies, mainly conducted under the auspices of ECVAM, and weight-of-evidence evaluations, mainly conducted under the auspices of ICCVAM. For example, by 2002, the ECVAM Scientific Advisory Committee (ESAC) had endorsed the successful outcomes of validation studies on 10 non-animal toxicity tests for chemicals, and had also made six statements on the application of the validation criteria and principles to biologicals (9), in line with the way in which the acceptance of alternative methods has evolved within the EC and the EU (10). ...
A plethora of regulations require that many chemicals and chemical products are tested for efficacy and/or toxicity. When permitted to operate effectively and without bias, the ECVAM/ICCVAM/OECD validation process can be used to independently establish that new animal and non-animal test procedures are sufficiently relevant and reliable for their stated purposes and should be considered for regulatory use. However, the validation process is under threat because of vested interests of various kinds, and it is clear that many currently-accepted animal tests and candidate animal and non-animal tests do not, and could never, meet the agreed criteria for necessity, test development, prevalidation, validation and acceptance. We therefore need an invalidation process to parallel and protect the validation process, so that such methods could be independently reviewed and declared irrelevant and/or unreliable for their claimed purposes. An additional advantage of such a process would be that valuable resources would no longer be wasted in attempts to secure the acceptance of inherently inadequate tests.
... Issued from ethical considerations a strong aspiration of the modern world concerns the replacement of in vivo experiments with in vitro tests and in silico predictive models. A European Center for the Validation of Alternative Methods (ECVAM) looks into the applicability of validation process to a variety of tests procedures including new generation of tests, new technologies, computer-based models and expert systems (Worth et al. 2001). ...
... These stages reflect the sequence of steps to be performed for a prospective validation exercise. They are well documented in a number of publications (for example, [2][3][4][5]. The process proved to be successful and led to the regulatory acceptance of several alternative tests (summarised in 6). ...
The European Centre for the Validation of Alternative Methods (ECVAM) proposes to make the validation process more flexible, while maintaining its high standards. The various aspects of validation are broken down into independent modules, and the information necessary to complete each module is defined. The data required to assess test validity in an independent peer review, not the process, are thus emphasised. Once the information to satisfy all the modules is complete, the test can enter the peer-review process. In this way, the between-laboratory variability and predictive capacity of a test can be assessed independently. Thinking in terms of validity principles will broaden the applicability of the validation process to a variety of tests and procedures, including the generation of new tests, new technologies (for example, genomics, proteomics), computer-based models (for example, quantitative structure-activity relationship models), and expert systems. This proposal also aims to take into account existing information, defining this as retrospective validation, in contrast to a prospective validation study, which has been the predominant approach to date. This will permit the assessment of test validity by completing the missing information via the relevant validation procedure: prospective validation, retrospective validation, catch-up validation, or a combination of these procedures.
... The scientific purpose of a (Q)SAR should be self-evident from the nature of the response variable that is being predicted from one or more physicochemical descriptor variables. In contrast, the scientific purpose of an in vitro test has not always been apparent, unless the test has been associated with a so-called " prediction model " that makes the extrapolation from the endpoint(s) being measured to the endpoint of interest being predicted[19]. ...
Under the current chemicals legislation, the regulatory use of structure-activity relationships (SARs) and quantitative structure-activity relationships (QSARs), collectively referred to as (Q)SARs, for the assessment of chemicals is limited, partly due to concerns about the extent to which (Q)SAR estimates can be relied upon. On 29 October 2003, the European Commission adopted a legislative proposal that foresees the introduction of a new regulatory system for chemicals called REACH (Registration, Evaluation, and Authorisation of Chemicals), which will impose equivalent information requirements on both new and existing chemicals. For reasons of practicality, cost-effectiveness and animal welfare, it is envisaged that (Q)SARs will play an important role in the assessment of some 30,000 existing chemicals for which further information may be required under the REACH system. It will therefore be essential that the (Q)SAR models used will produce reliable estimates. To overcome the barriers in the acceptance of (Q)SARs for regulatory purposes, it is widely acknowledged that there needs to be international agreement on the principles of (Q)SAR validation, and that the process of (Q)SAR validation should be managed by independent organisations, with a view to providing independent advice to the regulators who make decisions on the acceptability of (Q)SARs. The European Centre for the Validation of Alternative Methods (ECVAM), which is part of the European Commission's Joint Research Centre (JRC), has a well-established role in providing independent scientific and technical advice to European policy makers. This paper describes progress made at an international level regarding the principles of validation, and explains the role of ECVAM regarding the practical validation of (Q)SARs.
... Eur.). Since its elaboration in 1964, 28 European countries (including the European Union) have signed the Convention of the Ph. Eur. ...
... ECVAM has established a procedure for promotion of the regulatory acceptance of alternative methods in the European Union (28), which clearly describes ECVAM's duty to advise the European Commission and the regulatory bodies of the Member States on the scientific validity (i.e. the relevance and reliability) of alternative methods, as well as on the independent assessment of alternative methods. Following the completion of an ECVAM prevalidation or validation study, a report on the outcome of the study is submitted to ECVAM, so that it can be communicated to, and considered by, the ESAC. ...
This paper summarises key activities initiated and the progress achieved between April 1993 and November 2002, in promoting the Three Rs in one of ECVAM's priority areas--the production and quality control of biologicals. These have included organising nine key workshops, financially supporting and/or participating in a number of prevalidation and/or validation studies, financial contributions and sponsorship to relevant international workshops, symposia and conferences, and financial support to the compilation of manuals, expert reports and training in test methods.
