Metabolism of β‐aminopropionitrile and its teratogenic activity in rats

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Abstract
The administration of β‐aminopropionitrile (BAPN) to pregnant rats induced various fetal anomalies including a high percentage of cleft palate. Following oral administration BAPN was found along with its deaminatedoxidized derivative cyanoacetic acid (CAA) in embryos, placentas, and maternal tissues, serum, and urine. BAPN levels reached a maximum in tissue and serum 6 hours after treatment, were maintained for about 3 hours more, then sharply declined to negligible amounts by 24 hours. CAA levels however gradually rose and high levels were still present at 24 hours. Similar amounts of BAPN were found in tissues after its administration on either day 14. 15, or 16 of gestation; however, only on day 15 was there a positive correlation between embryonic levels of BAPN and cleft‐palate production. Thus 6 hours after BAPN treatment on day 15 embryonic levels of 106, 42, or 16 μg BAPN per g of tissue corresponded to a cleft‐palate incidence of 98, 28, or 0% respectively. Oral administration of CAA produced no cleft palate even though high embryonic levels of CAA were attained. These data indicate that BAPN itself is teratogenic and that it acts within a narrow period of time on day 15 in producing cleft palate.