Further development of rodent whole embryo culture: solvent toxicity and water insoluble compound delivery system.

ABSTRACT

In order to study the in vitro embryotoxicity and dysmorphogenesis of water insoluble compounds, solvents or chemical delivery systems of low toxicity and teratogenicity to the developing embryo must be found. Therefore, day 10.5 rat embryos were cultured for 2 days in whole rat serum containing 0.1, 0.5 and 2.5 vol.% of ethyl alcohol, dimethylsulfoxide, acetone, Tween 80, corn oil and 10% acetone/90% corn oil. No adverse effects occurred with any of the solvents at the 0.1% concentration level. At 0.5% ethyl alcohol and Tween 80 significantly reduced embryonic growth and increased the incidence of embryonic abnormalities. With the exception of corn oil and acetone/corn oil, embryos cultured in media containing 2.5% of various solvents failed to grow, did not differentiate, and died during the culture period. Corn oil suspended in rat serum by use of ultrasound was non-toxic even at concentrations of 2.5% and 10%. Growth parameters of embryos cultured in serum containing corn oil were indistinguishable from controls and overall morphogenesis was good (particularly at 2.5%). The order of increasing embryotoxicity and dysmorphogenesis of the studied liquids was corn oil less than acetone/corn oil less than dimethylsulfoxide less than ethyl alcohol, acetone less than Tween 80. Any of the 4 water miscible solvents (at 0.1%) or a sonicated suspension of corn oil in serum (up to 2.5%) met the criteria of a non-toxic and non-teratogenic water insoluble compound delivery system for in vitro embryo culture.