Embryo-fetal developmental toxicity study of alpha-glycosyl isoquercitrin administered orally to New Zealand White rabbits

Abstract

An embryo-fetal survival and development study was conducted to augment the toxicity database for alpha-glycosyl isoquercitrin (AGIQ), a generally recognized as safe (GRAS) additive and flavor in food and beverages. In Phase I, 24 naturally mated New Zealand white (NZW) female rabbits per group were administered AGIQ by oral gavage at 0, 250, 500, or 1000 mg/kg/day once daily during gestation days 6–28, followed by necropsy. There was no evidence of maternal or fetal toxicity except for equivocal findings of unilateral absent kidney and ureter in one and two unrelated fetuses at 500 and 1000 mg/kg/day, respectively. To more thoroughly assess fetal kidney/ureter development, in Phase II groups of time mated NZW rabbits were administered AGIQ at 0, 500, or 1000 mg/kg/day, under the same conditions as Phase I. No occurrences of absent kidney/ureter were noted in the AGIQ-treated Phase II dams or fetuses; although, one control fetus had unilateral missing kidney/ureter. Given the lack of reproducibility following treatment with AGIQ in Phase II using 48 animals per group, the missing kidney/ureter observations in Phase I were considered unrelated to treatment. Since oral gavage administration of AGIQ to pregnant female NZW rabbits at dose levels of 250, 500, or 1000 mg/kg/day was well-tolerated with no adverse treatment-related effects on the maternal animal, pregnancy, or the developing conceptus, the no-observed-adverse-effect-level (NOAEL) for maternal toxicity and embryo-fetal survival, growth, and development was 1000 mg/kg/day.