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Exposure to ethylene oxide during the early zygotic period induces skeletal anomalies in mouse fetuses.

Exposure of mouse zygotes to ethylene oxide (EtO) has been shown to increase the incidence of external malformations among late fetuses [Generoso et al. (1987) Mutat. Res., 176:267-274; Rutledge and Generoso, (1989) Teratology, 39:563-572]. The present study was designed to determine whether EtO also affects the skeletal system. We report here the effects of varying times of exposure during the zygotic period on skeletal development. Female hybrid mice were injected intraperitoneally (IP) with 125 mg/kg EtO at 1, 3, 5, or 7 hr postmating. A positive control group consisted of female mice that were injected IP with 150 mg/kg EtO once daily between the 6th to 8th days of gestation. Day 17 fetuses were double-stained for "blind" examination of skeletal deviations and degree of ossification. Zygotic exposure to EtO significantly increased loss of conceptuses as well as the incidence of external defects, skeletal anomalies, and retarded ossification in live day 17 fetuses. An increase in the number of exposed fetuses with cleft sternum was observed with the highest rate (58.5%) occurring in fetuses whose mothers were exposed to EtO 3 hours postmating. Cleft sternum was seen in only 5% of fetuses exposed during the period of organogenesis and less than 1% of control fetuses. It is concluded that zygotic exposure to EtO produces a pattern of skeletal defects that differs from those observed following treatment with EtO during organogenesis.