Studies on the pharmacological bases of fetal toxicity of drugs. (V) Effect of different administration routes of trypan blue in rats

: The teratogenicity of trypan blue (TB) after both maternal and intrauterine administrations was studied in Wistar rats, and the following results were obtained: 1) The teratogenic dose of TB by maternal subcutaneous injection was found to be greater than 50 mg/kg, and the critical period was until day 10 of pregnancy (sperm = day 0). No teratogenicity was detected by oral administration of 250 mg/kg TB. 2) TB (250 micrograms/uterine horn) was injected into the uterine cavity on day 4 or 6 of pregnancy. An increase of intrauterine death without malformations was observed in both TB-treated groups. 3) TB was injected into the exocoelom. The incidences of malformed fetuses were 53% in the group injected with 2.5 micrograms/embryo TB on day 10 and 32% and 57% in the groups injected with TB at 1.0 and 2.5 micrograms/embryo on day 11, respectively. An increase of intrauterine death was observed in these groups. Types of malformations observed in these groups were abnormal tail, spina bifida and deformity of vertebrae, and were almost similar to those observed by maternal subcutaneous injection of TB. 4) A trace of TB was found microscopically in the frozen section of embryo after both subcutaneous and intraexocoelom injections of TB. These results suggest that TB acts directly on embryos to produce malformations.