Development of a Method for Assessing the Acute Toxicity of Chemicals on Early Post-Implantation Embryos

Abstract

The whole-embryo culture technique developed by New (1978) is being increasingly used in investigating the mode of action of embryopathic agents. Appropriately devised experiments make it possible to decide whether a substance can act directly on the conceptus (McGarrity et al. 1981) or whether its embryotoxic effect requires maternal mediation (Fantel et al. 1979). In some cases it has even proved possible to assess the relative effects of a drug and its principal human metabolites (Beck et al. 1984). However, growing rat embryos within their yolk sacs and adding putative embryopathic agents to the culture serum does not enable the investigator to distinguish a direct effect on embryonic tissue from one on the extra-embryonic membranes. Furthermore, when a substance crosses the extraembryonic membranes in only small quantities there is difficulty either in investigating the capacity of the embryonic tissues to detoxify and metabolise it or in developing a comprehensive picture of its pharmacokinetics and of possible target sites in the embryo. In an attempt to overcome these problems, and, in addition to assess acute direct embryo toxicity, a method was devised of injecting materials directly into the vitelline vessels of embryos in culture and observing their effect over a culture period of up to 6 h.