title: An integrated approach for detecting embryotoxicity and developmental toxicity of environmental contaminants using in vitro alternative methods.
abstract: The main available alternatives for testing embryotoxicity are cellular tests with stem cells and in vitro-ex vivo tests with embryos. In cellular tests, the most developed alternative is the embryonic stem cell test, while the most developed tests involving embryos are the zebrafish and whole embryo culture test. They are technically more complex than cellular tests, but offer the advantage of determining the expectable phenotypic alteration caused by the exposure. Many efforts are currently being made, basically through proteomic and genomic approaches, in order to obtain improvements in predictivity of these tests. Development is a very complex process, and it is highly unlikely that a single alternative test can yield satisfactory performance with all types of chemicals. We propose a step-wise approach where model complexity, and consequently technical skills and economical costs, gradually increase if needed. The first level would be run short cellular assays to detect effects in early differentiation stages. The second level would involve longer cellular embryotoxicity tests to search embryotoxicants that have an effect on late differentiation stages. The third stage would consider tests with embryos because they allow the determination of hazards based on molecular and morphological alterations, and not only on differentiating cells.
authors: Unidad de Toxicología y Seguridad Química, Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Elche, Spain. Electronic address: msogorb@umh.es.
authors: Miguel A
authors: MA
authors: Sogorb
authors: Unidad de Toxicología y Seguridad Química, Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Elche, Spain; Johns Hopkins University, Bloomberg School of Public Health, CAAT, Baltimore, USA.
authors: David
authors: D
authors: Pamies
authors: Centre de Recerca en Toxicologia (UTOX-CERETOX), Parc Científic de Barcelona, Barcelona, Spain.
authors: Joaquín
authors: J
authors: de Lapuente
authors: Unidad de Toxicología y Seguridad Química, Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Elche, Spain; Chemical Assessment and Testing Unit, Institute for Health and Consumer Protection, DG Joint Research Centre, European Commission, Spain.
authors: Carmen
authors: C
authors: Estevan
authors: Unidad de Toxicología y Seguridad Química, Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Elche, Spain.
authors: Jorge
authors: J
authors: Estévez
authors: Unidad de Toxicología y Seguridad Química, Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Elche, Spain.
authors: Eugenio
authors: E
authors: Vilanova
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects*; D053595:Embryonic Stem Cells / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D005333:Fetus / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D040901:Proteomics; D051381:Rats; D015027:Zebrafish / Q000196:embryology
chemical_list: D004785:Environmental Pollutants
keywords: Alternative tests; Embryonic stem cell test; Embryotoxicity; Teratogenicity; WEC; Zebrafish test