Ema M, Harazono A, Miyawaki E, Ogawa Y
National Institute of Health Sciences, Osaka Branch, 1-1-43 Hoenzaka, Chuo-ku, Osaka 540, Japan.
Arch Environ Contam Toxicol. 1997 Jul;33(1):90-6. doi: 10.1007/s002449900228.
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.
本研究的目的是通过在器官形成期的某一天单次给药来确定氯化三丁基锡（TBTCI）致畸性的敏感日。在妊娠第7天、第8天或第9天，给怀孕大鼠经胃插管单次给予100 mg/kg的TBTCI；在妊娠第7天、第8天、第9天、第10天、第11天、第12天、第13天、第14天或第15天，给予200 mg/kg的TBTCI。所有TBTCI处理组给药后立即的母鼠体重增加显著减少。在妊娠第7天、第8天和第9天给予100和200 mg/kg的TBTCI以及在第10天和第11天给予200 mg/kg的TBTCI后，着床后丢失的发生率显著增加。当在第8天给予100和200 mg/kg的TBTCI以及在第11天、第12天、第13天和第14天给予200 mg/kg的TBTCI时，检测到有外部畸形胎儿的发生率显著增加，最明显的影响发生在妊娠第13天给药后。腭裂仅在器官形成后期给药后观察到。可以得出结论，TBTCI发育毒性的表现和敏感性随给药时的发育阶段而变化，并且TBTCI在妊娠第8天和第11 - 14天对致畸性具有双相敏感性。
