REPROTECT
Development of a novel approach in hazard and risk assessment of reproductive toxicity by a combination and application of in vitro, tissue…..
Informazioni Generali
- Coordinatore:
- UNIV. TUEBINGEN (Germania)
- Responsabile ENEA:
- SPANO' MARCELLO - SSPT-TECS-BIORISC (CASACCIA)
- Ruolo ENEA:
- PARTNER
- Sito WEB:
- http://www.reprotect.eu/
Descrizione e Attività
Descrizione Generale
Validated alternative test methods are urgently required for safety toxicology of drugs, chemicals and cosmetics. While some animal tests for topical toxicity have been successfully replaced one by one by alternative methods, systemic toxicities require new test strategies in order to achieve an adequate safety level of the consumer. In the project, ECVAM takes the lead to manage the development of a conceptual framework in the area of reproductive toxicity. The involvement of all stakeholders in the Project Board including the European Consensus Platform on Alternatives (ECOPA), European regulators, OECD, and Industry guarantees an efficient problem solving approach. Reproductive toxicity offers the opportunities that: i) a substantial number of animals are currently required in in-vivo assays; ii) the reproductive system can be broken down into well-defined sub-elements covering the reproductive cycle; iii) a number of pioneering alternatives have already been developed; and iv) the same animal experiments are carried out for drugs, chemicals and cosmetics.
The project is composed of four elements, i.e.
a) technological development of in vitro and
b) sensor technologies
c) the strategical development of a conceptual framework
d) the dissemination and implementation activities.
The project will develop the concepts required to compose testing strategies via the continuous implementation of novel in vitro and in silico alternatives. Problems to be solved include the development of substantial numbers of alternative test methods making use of advanced technologies. This approach requires the dimensions of a transnational Integrated Project, involving some of the most prominent reproductive toxicity research groups in the EU, close monitoring by and input from the regulatory community and professional managerial steering. In return, it offers the realistic opportunity to achieve a substantial reduction of animal experiment.
Attività svolta da ENEA
Establishment and prevalidation of a high throughput test system for detecting chemical effects on bull spermatozoa using high throughput tests such as the flow cytometric Sperm Chromatin Structure Assay (SCSA) and the Comet assay.
ENEA has developed ReProComet (Repair Proficient Comet assay), a test which can circumvent the sperm intrinsic repair deficiency by providing them from an exogenous source such as a cell extract. Our working hypothesis was that the repair enzymes present in the extracts could initiate the removal of chemically induced adducts on sperm DNA, thus forming the DNA strand breaks eventually detectable by the Comet assay. Sperm samples were treated in vitro with a variety of well known mutagenic chemicals and standard Comet assay was run in parallel with the ReProComet. In most cases, a clear-cut dose-dependent effect was measured only after the addition of the cell extract, demonstrating that ReproComet is effectively improving the ability of the standard Comet assay in detecting in vitro chemically induced DNA damage on spermatozoa.
Programmi Europei
- Programma:
- Sesto Programma Quadro UE (2002-2006) → SCIENZE DELLA VITA (2002-2006) (IP - Progetto Integrato)
Dati Finanziari (in euro)
Costo Eleggibile
- Progetto:
- 13.500.250,00
- ENEA:
- 515.765,00
Contributo
- Al progetto:
- 9.100.000,00
- A ENEA:
- 257.882,00
Durata del Progetto
- Anno di stipula e Durata:
- 2004 - 48 mesi
- Periodo:
- 01-07-2004 → 30-06-2008