Developmental toxicity testing from animal towards embryonic stem cells.
Developmental toxicology is the study of undesirable effects on the development of the organism, which may result from exposure before conception, from the period of prenatal development, or postnatally during the time of sexual maturation. The principal manifestations of developmental toxicity include: embryolethality, malformations, growth retardation, and functional impairment. In 2001, the European Commission published the future chemicals policy entitled "White Paper: Strategy for a Future Chemicals Policy". The new regulation requires a toxicological evaluation with strong emphasis on reproductive toxicity, by using in vitro methods, especially for those chemicals marketed at more than 1 ton per year. For this reason, the establishment of in vitro models capable of detecting major undesirable manifestations in the fetus, are urgently required. The aim of the present review is to explore the capacity of existing in vitro systems, based on embryonic stem (ES) cells, to identify embryotoxicity with a focus on specific effects such as teratogenicity and growth retardation. In addition, we discuss the possibility to adapt the mouse ES cells based tests to human ES cells, avoiding inter-species variations in developmental toxicity studies and address related ethical issues. Considering the different manifestations of developmental toxicity, only a battery of in vitro tests will provide the necessary information for regulatory developmental toxicity assessment.
Pellizzer
Cristian
C
European Centre for the Validation of Alternative Methods, Institute for Health and Consumer Protection, Joint Research Centre, Ispra, Italy.
Bremer
Susanne
S
Hartung
Thomas
T
D000826:Animal Testing Alternatives / Q000379:methods* / Q000639:trends; D000818:Animals; D002455:Cell Division; D000013:Congenital Abnormalities; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D014116:Toxicology / Q000379:methods*