Safety Evaluation And Risk Assessment Ofd-Limonene

Abstract

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 α(2u)-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-limonene have not been reported. The reference dose (RfD), the no-observed-adverse-effect level (NOAEL), and the systemic exposure dose (SED) were determined and found to be 2.5 mg/kg/d, 250 mg/kg//d, and 1.48 mg/kg/d, respectively. Consequently, the margin of exposure (MOE = NOAEL/SED) of 169 was derived based upon the data, and the hazard index (HI = SED/RfD) for d-limonene is 0.592. Taking into consideration conservative estimation, d-limonene appears to exert no serious risk for human exposure. Based on adverse effects and risk assessments, d-limonene may be regarded as a safe ingredient. However, the potential occurrence of skin irritation necessitates regulation of this chemical as an ingredient in cosmetics. In conclusion, the use of d-limonene in cosmetics is safe under the current regulatory guidelines for cosmetics.

Essential Oils Chemistry

“…(+)-Limonene, the enantiomer of orange and lemon peels, has a lemon-like odor making it attractive as an additive in cosmetics and foods (Kim et al 2013). This enantiomer is the most abundant in plants.…”

Toxicity and Efficacy of Two Emulsifiable Concentrates of 2-Tridecanone against Red Imported Fire Ants

“…Although, d-Limonene has been designated as a chemical with low toxicity based upon lethal dose (LD 50 ) and repeated-dose toxicity studies when administered orally to animals, skin irritation or sensitizing potential was reported following widespread use of this agent in various consumer products [37]. Vapor pressure for 2-tridecanone and d-limonene is 0.0164 and 1.96 mmHg at 25˚C respectively, indicating that 2-tridecanone is much less volatile than d-limonene, indicating that 2-tridecanone will cause less potential vapor hazard in work places.…”

Reversing Translational Suppression and Induction of Toxicity in Pancreatic Cancer Cells Using a Chemoprevention Gene Therapy Approach

“…This compound has a low toxicity profile and has been shown to be safe when used in humans. Adverse effects reported include skin irritation when D-limonene was used in cosmetic products (Kim et al, 2013). As a systemic therapy, this compound has been used in humans in clinical trials at up to 15 gm/day without major toxicities being observed.…”