Rat postimplantation embryo culture as a tool for internal dose modelling in embryotoxicity risk assessment

Abstract

De bruikbaarheid van de postimplantatie embryokweek voor interne dosis-modellering van embryotoxiciteit werd geevalueerd met carbamazepine als modelstof. Blootstelling via het kweekmedium leidde tot neuraalbuisdefecten, en blootstelling via amnionholte of exocoeloom veroorzaakte slechts lokale effecten. In overeenstemming hiermee was carbamazepine alleen detecteerbaar in embryonaal weefsel na blootstelling via het kweekmedium. Derhalve is de dosering via het kweekmedium de relevante blootstelling voor interne dosismodellering voor embryotoxische effecten en extrapolatie daarvan voor humane risicoevaluatie.<br>

The usefulness of postimplantation embryo culture for internal dose modelling in embryotoxicity testing was investigated using carbamazepine as a model compound. Exposure via the culture medium resulted in neural tube defects, whereas exposure via the amniotic or exocoelomic spaces caused local effects only. In accordance with these findings, only after culture medium exposure were amounts of carbamazepine detectable in the embryonic tissues. It is concluded that the dose taken up from the culture medium is the relevant dose to be used for internal dose modelling for embryotoxic effects and their extrapolation for human risk assessment.<br>