Cardiovascular teratogenicity of terbutaline and ritodrine in the chick embryo.

OBJECTIVE: We determined the teratogenic effects of terbutaline and ritodrine, both beta 2-sympathomimetic agonists, on the stage 24 (4-day) chick embryo. STUDY DESIGN: We used a topical method of application of terbutaline or ritodrine to the stage 24 chick embryo in ovo. Doses of terbutaline ranged from 5.5 x 10(-10) to 6.5 x 10(-9) mol per embryo, and ritodrine doses ranged from 4.6 x 10(-11) to 4.6 x 10(-8) mol per embryo. To further determine the pharmacologic nature of the teratogenic potential of terbutaline or ritodrine, the experiments were repeated after pretreatment with butoxamine hydrochloride, a preferential beta 2-antagonist, or metoprolol tartrate, a preferential beta 1-antagonist, 4 hours before application of terbutaline or ritodrine. RESULTS: Terbutaline treatment was associated with significantly higher rates of anomalies than in controls at all dosages used, whereas ritodrine induced significantly more anomalies at or above doses of 4.6 x 10(-9) mol per embryo. At an equimolar dose pretreatment with butoxamine hydrochloride significantly reduced the cardiovascular teratogenic effects of terbutaline and ritodrine. Pretreatment with metoprolol tartrate at any dose did not significantly reduce terbutaline's potential. Metoprolol, at doses tenfold or 100-fold higher than ritodrine, was able to significantly reduce the teratogenic effects of ritodrine. CONCLUSIONS: Our data suggest that terbutaline and ritodrine are teratogenic in the chick and that these agents exert their teratogenic effects primarily through stimulation of the beta 2-adrenergic receptor.

Teratogenesis associated with oxydemeton-methyl in the stage 12 chick embryo.

The teratogenic potential of oxydemeton-methyl (ODM) was investigated using a stage specific localized topical method of application to the stage 12 chick embryo. A dose of 0.01, 0.05, 0.10, 0.50, 1.0, or 2.0 mg/embryo was applied to the vitelline membrane directly above the stage 12 embryo. The embryo was then returned to the incubator and monitored daily until stage 41 (15 day). At stage 41 the embryo was autopsied and examined for gross external and internal malformations, wet weight, and crown-rump length. Experimental data was compared to unopened and saline treated controls. At doses less than 0.50 mg/embryo, survival rates were high (> 80%) but when that dose was exceeded, the survival rate fell significantly (P < 0.001). A dose-dependent increase in malformation rate was seen in all treatment groups with 0.10 mg/embryo, producing a maximum malformation rate (19/33) with minimum mortality (3/36). Crown-rump lengths and wet weights were significantly less than controls in all treatment groups (P < 0.001). Anomalies were primarily seen in the musculoskeletal (ventral midline, limb, and neck) and cardiovascular (ventricular septum and aortic arches) systems. Thoracogastroschisis and ventricular septal defects were the most common combination of malformations. Our data suggest that ODM is teratogenic when topically applied to the stage 12 chick embryo.