Safety Evaluation And Risk Assessment Of d-Limonene

d-Limonene, a major constituent of citrus oils, is a monoterpene widely used as a flavor/fragrance additive in cosmetics, foods, and industrial solvents as it possesses a pleasant lemon-like odor. d-Limonene has been designated as a chemical with low toxicity based upon lethal dose (LD50) and repeated-dose toxicity studies when administered orally to animals. However, skin irritation or sensitizing potential was reported following widespread use of this agent in various consumer products. In experimental animals and humans, oxidation products or metabolites of d-limonene were shown to act as skin irritants. Carcinogenic effects have also been observed in male rats, but the mode of action (MOA) is considered irrelevant for humans as the protein α2u-globulin responsible for this effect in rodents is absent in humans. Thus, the liver was identified as a critical target organ following oral administration of d-limonene. Other than the adverse dermal effects noted in humans, other notable toxic effects of d-li...