Histopathological changes induced by geraniol: a route-comparative toxicity study in rats following single and 14-day repeated doses

Abstract

Geraniol, a widely used substance in pharmacological research, fragrance, and cosmetic industries, but it is devoid of safety profile. This study aimed to evaluate the acute toxicity of geraniol using 24 h and 14 d toxicity models via oral (p.o.), intraperitoneal (i.p.), and intranasal (i.n.) routes to establish its toxicological thresholds and potential mechanism of toxicity via in-silico approach. In 24 h acute toxicity study, geraniol administered at 2500 mg/kg (p.o.), 5000 mg/kg (p.o.), and 100 mg/kg (i.n.) doses did not cause mortality. While i.p. administration resulted in dose-dependent mortality, with an LD50 of 950 mg/kg determined for this route. The 14 d toxicity study revealed no mortality at doses up to 400 mg/kg (p.o.), 150 mg/kg (i.p.), and 50 mg/kg (i.n.), highlighting its safety at these thresholds. Behavioural, hematological, and biochemical analyses revealed significant hepatotoxic effects, particularly at higher doses administered through the p.o. and i.p. routes, accompanied by hepato-histopathological alterations. These effects may be associated with potential CYP2E1-mediated mechanisms, implicating metabolic activation as a contributor of geraniol-induced hepatoxicity. Other vital organs, including brain, lungs, heart, and kidneys, remained unaffected in both studies. This comprehensive investigation identifies the safety limits of geraniol through different routes of administration and underscores its hepatotoxic potential at elevated doses. These findings emphasize the need for dose optimization and further mechanistic studies to evaluate the relevance of CYP2E1 involvement. Geraniol demonstrates a favorable safety profile within defined limits, but its hepatotoxic effects at higher doses highlight the importance of careful monitoring in therapeutic and commercial applications.