Repeated oral administration of gamma-aminobutyric acid (GABA) does not cause reproductive or developmental toxicity in rats

Gamma-aminobutyric acid (GABA) occurs naturally in a variety of foods and has a long history of dietary consumption, yet its effects on reproduction and development have not been evaluated in a guideline-compliant toxicological study. We examined the reproductive and developmental endpoints of repeated oral gavage GABA administration in Sprague Dawley (SD) rats using an enhanced OECD (Organization for Economic Co-operation and Development) 421-compliant design, in which groups of 20 males and 20 females received daily doses of 0, 625, 1250, or 2500 mg/kg/day GABA. The OECD 421 protocol was modified to include male dosing lasting 89-92 days, covering the pre-mating, mating, and post-mating periods. Females were dosed for 50-63 days from pre-mating through Lactation Day 12, with protocol-based adjustments for reproductive status. No treatment-related mortality, systemic toxicity, or organ pathology was observed. Estrous cyclicity, mating performance, fertility index, implantation, gestation, parturition, and maternal behavior remained unchanged. Offspring viability and developmental landmarks showed no treatment-related differences. Hormonal assessments revealed no pattern indicative of reproductive or thyroid disruption. Overall, repeated oral GABA administration in SD rats up to 2500 mg/kg/day produced no adverse effects on parental health, reproductive outcomes, or offspring development.