|IDENTIFICATION AND USE: D-Limonene is a colorless liquid or oil with citrus odor. 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. It is registered for pesticide use in the USA but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. D-Limonene is also used as gallstone solubilizer in animals and humans. |
HUMAN EXPOSURE AND TOXICITY: Skin irritation or sensitizing potential was reported following widespread use of this agent in various consumer products. In humans, oxidation products or metabolites of d-limonene were shown to act as skin irritants. The potential occurrence of skin irritation necessitates regulation of this chemical as an ingredient in cosmetics. In humans, d-limonene has demonstrated low toxicity after single and repeated dosing for up to one year. D-Limonene was reported to significantly damage and increase permeability of membranes of human lung fibroblasts.
ANIMAL STUDIES: In experimental animals oxidation products or metabolites of d-limonene were shown to act as skin irritants. 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. Carcinogenic effects have also been observed in male rats, but the mode of action (MOA) is considered irrelevant for humans as the protein alpha(2u)-globulin responsible for this effect in rodents is absent in humans. d-Limonene induced hyaline droplet nephropathy in male rats. The liver was identified as a critical target organ following oral administration of d-limonene. D-Limonene (2363 mg/kg, orally) given to mice for 6 days from day 7-12 of gestation decreased body weight gain and increased incidence of abnormal bone formation in fetuses. D-Limonene also decreased body weight gain in male offspring; however, the toxicity of d-limonene was not severe. D-Limonene was not mutagenic in four strains of Salmonella typhimurium (TA 98, TA 100, TA 1535, or TA 1537), did not significantly increase the number of trifluorothymidine-resistant cells in the mouse L5178Y/TK + or - assay, and did not induce chromosomal aberrations or sister chromatid exchanges in cultured CHO cells. All assays were conducted in the presence and absence of exogenous metabolic activation.