From NuGOwiki
The NuGOwiki Metabolite Database is a joint initiative of NuGO and HMDB
| Taxonomy Navigation Box; search by |
|
All Metabolites | Biochemical | Nutritional | Functional | Metabolic Pathways | Diseases | Phenotypes | Physiological Processes | Protein |
| (-)-Limonene | |
|---|---|
 | |
| Chemical Name | (4S)-1-methyl-4-prop-1-en-2-yl-cyclohexene |
| Chemical Formula | C10H16 |
| CAS Number | 5989-54-8 |
| Chemical Information | HMDB03375 |
| Biochemical Taxonomy |
|
| Functional Taxonomy | Not Available |
| Nutritional Taxonomy | Not Available |
| Metabolic Pathways | Not Available |
| Biofluid Location |
|
| Tissue Location |
|
| Normal Biofluid Concentrations |
|
| Normal Tissue Concentrations | Not Available |
| Diseases / Conditions Related to Nutrition | Not Available |
| Other (Monogenic Disorders) | Not Available |
| Abnormal Biofluid Concentrations | Not Available |
| Abnormal Tissue Concentrations | Not Available |
| Physiological Processes | Not Available |
| Authors: | |
| Affiliations: |
Contents |
Introduction
guidelines
The monoterpene d-limonene is a naturally occurring chemical which is the major component in oil of orange. Currently, d-limonene is widely used as a flavor and fragrance and is listed to be generally recognized as safe in food by the Food and Drug Administration (21 CFR 182.60 in the Code of Federal Regulations, U.S.A.). Recently, however, d-limonene has been shown to cause a male rat-specific kidney toxicity referred to as hyaline droplet nephropathy. Furthermore, chronic exposure to d-limonene causes a significant incidence of renal tubular tumors exclusively in male rats. Although d-limonene is not carcinogenic in female rats or male and female mice given much higher dosages, the male rat-specific nephrocarcinogenicity of d-limonene may raise some concern regarding the safety of d-limonene for human consumption. A considerable body of scientific data has indicated that the renal toxicity of d-limonene results from the accumulation of a protein, alpha 2u-globulin, in male rat kidney proximal tubule lysosomes. This protein is synthesized exclusively by adult male rats. Other species, including humans, synthesize proteins that share significant homology with alpha 2u-globulin. However, none of these proteins, including the mouse equivalent of alpha 2u-globulin, can produce this toxicity, indicating a unique specificity for alpha 2u-globulin. With chronic exposure to d-limonene, the hyaline droplet nephropathy progresses and the kidney shows tubular cell necrosis, granular cast formation at the corticomedullary junction, and compensatory cell proliferation. Both d-limonene and cis-d-limonene-1,2-oxide (the major metabolite involved in this toxicity) are negative in vitro mutagenicity screens. Therefore, the toxicity-related renal cell proliferation is believed to be integrally involved in the carcinogenicity of d-limonene as persistent elevations in renal cell proliferation may increase fixation of spontaneously altered DNA or serve to promote spontaneously initiated cells. The scientific data base demonstrates that the tumorigenic activity of d-limonene in male rats is not relevant to humans. The three major lines of evidence supporting the human safety of d-limonene are (1) the male rat specificity of the nephrotoxicity and carcinogenicity; (2) the pivotal role that alpha 2u-globulin plays in the toxicity, as evidenced by the complete lack of toxicity in other species despite the presence of structurally similar proteins; and (3) the lack of genotoxicity of both d-limonene and d-limonene-1,2-oxide, supporting the concept of a nongenotoxic mechanism, namely, sustained renal cell proliferation. (PMID: 2024047)
Biological Function
Catabolism
Diseases / Conditions Related to Nutrition
Other (Monogenic) Disorders