Effect of the day of administration on the developmental toxicity of tributyltin chloride in rats.

The objective of this study was to determine the susceptible day for the teratogenicity of tributyltin chloride (TBTCI) by a single administration on one of the days during organogenesis. Pregnant rats were given a single dose of TBTCI by gastric intubation at 100 mg/kg on either day 7, day 8, or day 9 and at 200 mg/kg on either day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, or day 15 of pregnancy. The maternal body weight gain in the period immediately following administration in all TBTCI-treated groups was significantly decreased. A significant increase in the incidence of postimplantation loss was found after administration of TBTCI on day 7, day 8, and day 9 at 100 and 200 mg/kg and on day 10 and day 11 at 200 mg/kg. A significantly increased incidence of fetuses with external malformations was detected when TBTCI was given on day 8 at 100 and 200 mg/kg and on day 11, day 12, day 13, and day 14 at 200 mg/kg, and the most pronounced effect occurred after administration on day 13 of pregnancy. Cleft palate was observed exclusively after administration during late organogenesis. It could be concluded that the manifestation and susceptibility of the developmental toxicity of TBTCI vary with the developmental stages at the time of administration and that TBTCI has the biphasic sensitivity to teratogenicity on day 8 and days 11-14 of pregnancy.