International Agency for Research on Cancer (IARC) - Summaries & Evaluations

For definition of Groups, see Preamble Evaluation.

VOL.: 56 (1993) (p. 135)
CAS No.: 5989-27-5
Chem. Abstr. Name: (R)-1-Methyl-4-(1-methylethenyl)cyclohexene

5.1 Exposure data

d-Limonene is found widely in citrus and many other plant species and is a major constituent of many essential oils. It is used extensively as a component of flavourings and fragrances, as a chemical intermediate and as an insect repellant. Widespread exposures occur through consumption of fruits, vegetables and products containing essential oils. Consumption of d-limonene has been estimated to be 0.2-2 mg/kg bw per day.

5.2 Human carcinogenicity data

No data were available to the Working Group.

5.3 Animal carcinogenicity data

d-Limonene has been tested for carcinogenicity by oral gavage in one study in mice and one study in rats. In mice, no treatment-related tumour was observed. It significantly increased the combined incidence of renal-cell adenomas and carcinomas and induced renal tubular hyperplasia in male rats.

In a two-stage experiment, oral treatment with d-limonene after administration of N-nitrosoethylhydroxyethylamine enhanced the development of renal adenomas and renal tubular hyperplasia in male Fischer 344 rats, which synthesize a_2m-globulin, but not in male NBR rats, in which there is no evidence that a_2m-globulin is synthesized in measurable quantities.

5.4 Other relevant data

In men, oral intake of d-limonene induced transient proteinuria. d-Limonene induced nephrotoxicity in male Fischer 344 but not NBR rats.

No data were available on the genetic and related effects of d-limonene in humans. In a small number of studies with a variety of endpoints, d-limonene showed no evidence of genotoxic activity.

5.5 Evaluation

No data were available on the carcinogenicity of d-limonene to humans.

There is limited evidence in experimental animals for the carcinogenicity of d-limonene.

Overall evaluation

d-Limonene is not classifiable as to its carcinogenicity to humans (Group 3).

For definition of the italicized terms, see Preamble Evaluation.

Subsequent evaluation: Vol. 73 (1999)

Synonyms

• Cajaputene
• Carvene
• Cinene
• (+)-Dipentene
• d-(+)-Limonene
• D-(+)-Limonene
• (+)-Limonene
• (R)-Limonene
• (R)-(+)-Limonene
• (+)-para-Mentha-1,8-diene
• (R)-(+)-para-Mentha-1,8-diene
• 1-Methyl-4-isopropenyl cyclohexene-1
• Refchole

    See Also:
       Toxicological Abbreviations
       Limonene, d-  (IARC Summary & Evaluation, Volume 73, 1999)