Effects of Exposure Period on the Developmental Toxicity of 2-Bromopropane in Sprague-Dawley Rats
2008
Shin, I.S. (Chonnam National University, Gwangju, Republic of Korea) | Lee, J.C. (Chonnam National University, Gwangju, Republic of Korea) | Kim, K.H. (Chonnam National University, Gwangju, Republic of Korea) | Ahn, T.H. (Chonnam National University, Gwangju, Republic of Korea) | Bae, C.S. (Chonnam National University, Gwangju, Republic of Korea) | Moon, C.J. (Chonnam National University, Gwangju, Republic of Korea) | Kim, S.H. (Chonnam National University, Gwangju, Republic of Korea) | Shin, D.H. (Chonnam National University, Gwangju, Republic of Korea) | Kim, J.C. (Chonnam National University, Gwangju, Republic of Korea)
Recently we reported that 2-bromopropane (2-BP) has maternal toxicity, embryotoxicity, and teratogenicity in Sprague-Dawley rats. The aims of this study are to examine the potential effects of 2-BP administration on pregnant dams and embryo-fetal development, and to investigate the effects of metabolic activation induced by phenobarbital (PB) on developmental toxicities of 2-BP. Pregnant rats received 1000 mg/kg/day subcutaneous 2-BP injections on gestational days (GD) 6 through 10 (Group Ⅱ and Group Ⅲ) or 11 through 15 (Group Ⅳ). Pregnant rats in Group Ⅲ received an intraperitoneal PB injection once daily at 80 mg/kg/day on GD 3 through 5 for induction of the liver metabolic enzyme system. Control rats received vehicle injections only on GD 6 through 15. All dams underwent caesarean sections on GD 20 and their fetuses were examined for external, visceral, and skeletal abnormalities. Significant adverse effects on pregnant dams and embryo-fetal development were observed in all the treatment groups, and the maternal and embryo-fetal effects of 2-BP observed in Group Ⅱ were higher than those seen in Group Ⅳ. Conversely, maternal and embryofetal developmental toxicities observed in Group Ⅲ were comparable to those seen in Group Ⅱ. These results suggest that the potential effects of 2-BP on pregnant dams and embryo-fetal development are more likely in the first half of organogenesis (days 6~10 of pregnancy) than in the second half and that the metabolic activation induced by PB pre-treatment did not modify the developmental toxic effects of 2-BP in rats.
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