144 TERATOGENESIS

It is concluded that the presence of the aromatic ring appears to be essential for terato- genie as well as pharmacological activity.

783, Teratogenicity of trypan blue Beck, F. & Lloyd, J. B. (1964). Dosage-response curves for the teratogenic activity of trypan blue. Nature, Lond. 201, 1136.

The authors of this report have published several papers on the teratogenic action of trypan blue (I) (Cited in F.C.T. 1964, 2, 85 & 520) and have shown that following adminis- tration of I, most foetal deaths are secondary to foetal malformation and that the resorption rate rises and the malformation rate falls as pregnancy advances. Dosage-response curves have now been constructed for I in rats and the optimum teratogenic dose (OTD) and tera- togenic dose range (TDR) have been defined for the route of administration and strain of rat used.

Subcutaneous injections of I in the free acid form were given to inbred Wistar rats on day 8-5 of gestation at dosage levels of 5, 12.5, 25, 37-5, 50, 75, 100 or 200 mg/kg. The controls received 5 ml/kg isotonic saline. After sacrifice on day 20-5, foetal resorption sites were counted and foetuses examined for external malformations. The OTD is the dose which, given at the appropriate stage of pregnancy, produces the maximum number of malformed young at term. Below this level, the dosage-response curves for resorptions and malformations are roughly parallel, rising with increasing dose. Above it the curves diverge, the resorption rate increasing at the expense of both normal and abnormal survivors. The OTD in this experiment was approximately 50 mg/kg and the TDR 5-100 mg/kg. It is doubtful whether there is in fact a true lower limit to this range, as no threshold limit has been demonstrated below which I is inactive.