Induction of terata in hamsters by solanidane alkaloids derived from Solanum tuberosum

The potential induction of terata by solanidanes has been of public health concern since a report in 1972 hypothesized that certain birth defects in humans could be attributed to ingestion of blighted potatoes. The potential teratogenicity of solanidane alkaloids from potatoes and tomatoes in domestic livestock had been considered even earlier. In the present report, oral administration of the steroidal alkaloid glycosides alpha-solanine and alpha-chaconine and their aglycone solanidine is shown to induce craniofacial malformations (exencephaly, encephalocele, and anophthalmia) in Syrian hamsters. All three alkaloids, that were either isolated or obtained by hydrolysis from Solanum tuberosum (var. Kennebec) sprouts, possessed the 22-(R),25(S)-configuration in the indolizidine moiety with no other isomers present. Toxicity constraints precluded administration of dosages high enough to induce statistically significant levels of terata in litters dosed with alpha-chaconine and permitted the attainment of only marginal statistical significance for alpha-solanine. However, malformation induction at p < 0.005 was observed in litters upon dosing both the nontoxic aglycone solanidine and the derivative solanidine N-oxide at higher levels. The relatively high teratogenicity of nontoxic solanidine, compared to the glycosides, demonstrates that terata induction by solanidanes is not due to maternal toxicity nor is the oligosaccharide portion of steroidal alkaloid glycosides required to facilitate passage of the teratogen to the fetus. The teratogenicity of solanidine N-oxide, a putative metabolite, suggests that N-oxidation is not an effective mammalian detoxification pathway. Relative teratogenic potencies (RTP) were assigned to solanidanes by conversion of literature data to equimolar doses compared to the powerful Veratrum teratogen jervine and the nonteratogenic spirosolane tomatidine. RTP values are as follows: jervine (100), 22(S),-25(R)-solanidanes (50), alpha-chaconine (43), alpha-solanine (32), 22(R),25(S)-solanidine (32), solanidine N-oxide (32), 5 alpha,6-dihydrosolanidine (9), and tomatidine (0).