6-Aminonicotinamide-induced eye defects in rats.

The pathological changes and structural anomalies induced by 6-aminonicotinamide (6-AN) in the developing eye were studied in rats (Wistar and hooded randombred strain). The substance was administered in aqueous solution intraperitoneally (4 mg/kg on day 9--10 of pregnancy: 5 mg/kg on day 11 of pregnancy; 8 mg/kg on day 13--17 of pregnancy) and in physiological saline intraamniotically (0.01 ml of a 1% solution in physiological saline on day 15 of pregnancy). Embryos and foetuses from experimental series and from untreated control series were macro- and microscopically examined on day 10--20 of pregnancy. Control foetuses from mothers injected with distilled water on day 9--17 of pregnancy were examined on day 20 of pregnancy. The pathological changes and structural anomalies detected at successive developmental stages are presented. They reveal an obvious phase specificity and attest that the same substance may act through both of the main teratogenic pathways hypothetically put forward by Menkes et al. (1970). Based upon the present findings (and some previous results obtained in experiments with bisazo dyes) a working hypothesis is tentatively presented, as to the possible determination of the uni- or/and bilateral distribution of chemically induced developmental defects. In connection with some reversible or transitory pathological changes the role of recovery in teratogenesis is pointed out.