D-limonene

D-limonene does not currently hold FDA GRAS (Generally Recognized as Safe) status as a food additive, though it is permitted for use as a flavoring agent in food under FDA regulations (21 CFR 182.60). The compound is listed in the Code of Federal Regulations as a synthetic flavoring substance. In the European Union, D-limonene is permitted as a food flavoring and is listed in the Union List of authorized flavoring substances. The substance is also approved for use as a flavoring in other major markets including Canada and Australia. Its non-GRAS status does not indicate safety concerns but rather reflects the regulatory categorization pathway through which it is approved.

Toxicological evaluations of D-limonene have been conducted by organizations including the International Agency for Research on Cancer (IARC) and the Research Institute for Fragrance Materials (RIFM). A 2-year chronic toxicity study in rats demonstrated no carcinogenic potential. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) has reviewed available safety data on D-limonene and determined that it poses no safety concern at current levels of dietary exposure. Metabolism studies confirm that D-limonene is rapidly absorbed and metabolized, with no bioaccumulation in tissues. The LD50 (lethal dose for 50% of test population) in rats is approximately 4.6 g/kg body weight via oral administration, indicating low acute toxicity. Genotoxicity studies have shown negative results, and reproductive toxicity studies in animal models have not identified concerns. The concentration of D-limonene in food products is typically very low—often in the range of parts per million—which is substantially lower than concentrations used in toxicological research.