Teratologic and other embryotoxic effects of β-aminopropionitrile in rats

Increased resorption rates and decreased fetal weight were produced by intubating pregnant rats with various single (35001–4000 mg/kg) or multiple (2500–3000 mg/kg) doses of β‐aminopropionitrile (BAPN) during days 8–17 of gestation. The most embryotoxic gestational intervals were those that included day 15. Resorption (55% ) and ectocardia and/or gastroschisis (16%) resulted when 2500 mg/kg BAPN was administered on days 14–15, whereas no gross congenital malformations occurred when BAPN was administered before day 14. Higher doses of BAPN, such as 5000 m/kg, resulted mainly in fetal resorptions; 2500 mg/kg or greater on day 16 caused only cleft palate in most fetuses. Severe degrees of kyphoscoliosis, bony curvatures, and exostoses at muscleinsertion sites were observed when BAPN was given after day 16. The pathogenesis of these malformations is compatible with the known biochemical effect of BAPN — inhibition of crosslinking of both collagen and elastin — and in doing so: (a) could decrease the tensile strength of the anterior chest wall or abdominal wall to produce ectocardia and/or gastroschisis; (b) interfere with palate closure; and (c) produce osteolathyritic effects late in gestation which resemble the skeletal effects caused postnatally in young weanling animals given this agent.