Solid Preservative Preparation from Decolorized Ethanolic Extract of Ginggiang (Leea aequata L.): A 90-Day Subchronic Toxicity Study in Rats

Natural preservatives derived from medicinal plants require a thorough safety evaluation before they can be used in food. Ginggiang has traditionally been used by the Kuta indigenous community in Ciamis, West Java, Indonesia, to preserve palm sap; however, its safety profile has not been evaluated. In this study, a solid preservative preparation was developed from the decolorized ethanolic extract of ginggiang leaves (SPP-ED), and its safety profile was assessed after repeated oral administration. The study focused on subchronic oral toxicity and identified the target organs affected by repeated exposure to SPP-ED. In a 90-day experiment, both male and female Wistar rats received SPP-ED at doses of 45, 150, or 1500 mg/kg body weight per day. Satellite groups were included to evaluate recovery. Various parameters, including behavioral, hematological, biochemical, urinalysis, organ index, and histopathological evaluations, were systematically analyzed. No mortality was observed during the study. The results showed that subchronic exposure to SPP-ED had sex-specific effects: female rats experienced renal alterations, characterized by changes in urinalysis, elevated blood urea nitrogen and creatinine levels, and signs of tubular degeneration. In contrast, male rats exhibited pulmonary changes, including an increased lung-to-body weight ratio, alveolitis, and fibrosis. The D1 dose (45 mg/kg body weight/day) was the lowest dose at which potentially adverse histopathological changes were observed; however, a definitive NOAEL and LOAEL could not be established. Further studies using lower dose levels are warranted to better characterize the dose-response relationship and establish the NOAEL and LOAEL of SPP-ED.