A toxicological evaluation of geranylgeraniol

Area of Science:

• Toxicology
• Food Science
• Natural Products Chemistry

Background:

• Geranylgeraniol (GGOH), an isoprenoid from annatto seeds, is a mevalonate pathway intermediate with diverse biological roles.
• Limited toxicological data exists for food-grade GGOH, necessitating safety assessments.
• Annatto oil, rich in trans-GGOH, is used in food products.

Purpose of the Study:

• To evaluate the genotoxic potential of food-grade GGOH.
• To assess the subchronic oral toxicity of GGOH in rats.
• To identify potential target organs and establish safety thresholds.

Main Methods:

• Genotoxicity assessment using bacterial reverse mutation, in vitro mammalian chromosomal aberration, and in vivo mammalian micronucleus tests.
• A 90-day repeated-dose oral toxicity study in Hsd. Han Wistar rats (0, 725, 1450, 2900 mg/kg bw/day).
• Histopathological examination of target organs and determination of LOAEL and NOAEL.

Main Results:

• No evidence of mutagenicity or genotoxic activity was observed.
• Adverse effects, including forestomach irritation and liver changes, were noted in rats at all tested doses.
• The lowest observed adverse effect level (LOAEL) for local effects was 725 mg/kg bw/day.
• The no observed adverse effect level (NOAEL) for systemic effects was determined as 725 mg/kg bw/day.

Conclusions:

• Food-grade GGOH exhibits no genotoxic potential.
• GGOH can cause local forestomach effects and systemic liver toxicity at higher doses.
• A NOAEL of 725 mg/kg bw/day was established for systemic toxicity in rats.