Developmental and reproductive toxicity assessment of sporoderm-removed Ganoderma lucidum spores.

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INTRODUCTION: Ganoderma lucidum is a fungus used in traditional Chinese medicine with high medicinal value and is also widely used in modern healthcare. Its spores are reported to contain antitumor and anti-inflammatory properties, among other biological benefits; however, the thick spore wall limits its bioavailability. Sporoderm-removed Ganoderma lucidum spores (RGLS) offer improved bioavailability. However, data on their safety in pregnant and lactating populations remain limited, highlighting the need for developmental and reproductive toxicity (DART) assessment. We aimed to evaluate the developmental and reproductive safety of RGLS to support its clinical application in maternal and perinatal populations.

METHODS: Following ICH S5 (R3) guidelines, we conducted three non-clinical DART studies: embryo-fetal developmental (EFD) toxicity in rats, in vitro whole-embryo culture (WEC) in rabbits, and prenatal and postnatal toxicity (PPND) in rats. Female rats were administered RGLS (0.4, 1.2, and 4.0 g/kg/day) via oral gavage from gestation day (GD) 6 to GD17 (EFD) or to postnatal day (PND) 20. Rabbit embryos were cultured for 48 h in media containing 0.688, 0.963, and 1.238 mg/mL RGLS extract.

RESULTS: Our results showed no maternal toxicity, embryotoxicity, or teratogenicity in rats, apart from reversible drug-mixed feces. The offspring showed no adverse effects on growth, neurodevelopment (Morris water maze), or fertility. Rabbit embryos exhibited normal morphology and organ development. The no-observed-adverse-effect level of RGLS was 4.0 g/kg, which was approximately 20 times the intended clinical dose.

DISCUSSION: Overall, our study supports the safe use of RGLS in clinical applications for pregnant and lactating women, indicating that it can be added to a healthy diet.