3,026
Views
131
CrossRef citations to date
0
Altmetric
Original Articles

Safety Evaluation And Risk Assessment Of d-Limonene

, , , , , , , , , , , , & show all
Pages 17-38 | Published online: 10 Apr 2013

REFERENCES

  • Alden , C. L. 1986 . A review of unique male rat hydrocarbon nephropathy . Toxicol.Pathol. , 14 : 109 – 111 .
  • Altshuller , A. P. 1983 . Review: Natural volatile organic substances and their effect on air quality in the United States . Atmos. Environ. , 17 : 2131 – 2165 .
  • Anderson , B. E. , Zeiger , E. , Shelby , M. D. , Resnick , M. A. , Gulati , D. , Ivett , J. L. and Loveday , K. 1990 . Chromosome aberration and sister chromatid exchange test results with 42 chemicals . Environ. Mol. Mutagen. , 16 : 55 – 137 .
  • Arey , J. , Winer , A. M. , Atkinson , R. , Aschmann , S. M. , Long , W. D. , Morrison , C. L. and Olszyk , D. M. 1991 . Terpenes emitted from agricultural species found in California's central valley . J. Geophys. Res. , 96 : 9329 – 9336 .
  • Ariyoshi , T. , Arakaki , M. , Ideguchi , K. , Ishizuka , Y. and Ide , H. 1975 . Studies on the metabolism of d-limonene (p-mentha-1, 8-diene): III . Effects of d-limonene on the lipids and drug-metabolizing enzymes in rat livers. Xenobiotica , 5 : 33 – 38 .
  • Bagley , D. , Gardner , J. , Holland , G. , Lewis , R. , Regnier , J. F. , Stringer , D. and Walker , A. 1996 . Skin irritation: Reference chemicals data bank . Toxicol. In Vitro , 10 : 1 – 6 .
  • Bicas , J. L. , Fontanille , P. , Pastore , G. M. and Larroche , C. 2008 . Characterization of monoterpene biotransformation in two pseudomonads . J. Appl. Microbiol. , 105 : 1991 – 2001 .
  • Borghoff , S. J. and Lagarde , W. H. 1993 . Assessment of binding of 2,4,4-trimethyl-2-pentanol to low-molecular-weight proteins isolated from kidneys of male rats and humans . Toxicol. Appl. Pharmacol. , 119 : 228 – 235 .
  • Borghoff , S. J. , Miller , A. B. , Bowen , J. P. and Swenberg , J. A. 1991 . Characteristics of chemical binding to alpha 2u-globulin in vitro—Evaluating structure–activity relationships . Toxicol. Appl. Pharmacol. , 107 : 228 – 238 .
  • Broitman , S. A. , Wilkinson , J. 4th , Cerda , S. and Branch , S. K. 1996 . Effects of monoterpenes and mevinolin on murine colon tumor CT-26 in vitro and its hepatic “metastases” in vivo . Adv. Exp. Med. Biol. , 401 : 111 – 130 .
  • Cachao , P. , Brandão , F. M. , Carmo , M. , Frazao , S. and Silva , M. 1986 . Allergy to oil of turpentine in Portugal . Contact Dermatitis , 14 : 205 – 208 .
  • Chen , H. , Chan , K. K. and Budd , T. 1998 . Pharmacokinetics of d-limonene in the rat by GC-MS assay . J. Pharm. Biomed. Anal. , 17 : 631 – 640 .
  • Christensson , J. B. , Johansson , S. , Hagvall , L. , Jonsson , C,. , Börje , A. and Karlberg , A. T. 2008 . Limonene hydroperoxide analogues differ in allergenic activity . Contact Dermatitis , 59 : 344 – 352 .
  • Christensson , J. B. , Forsstrom , P. , Wennberg , A. M. , Karlberg , A. T. and Matura , M. 2009 . Air oxidation increases skin irritation from fragrance terpenes . Contact Dermatitis , 60 : 32 – 40 .
  • Ciccioli , P. , Brancaleoni , E. , Cecinato , A. , Sparapani , R. and Frattoni , M. 1993 . Identification and determination of biogenic and anthropogenic volatile organic compounds in forest areas of northern and southern Europe and a remote site of the himalaya region by high-resolution gas chromatography–mass spectrometry . J. Chromatogr. A , 643 : 55 – 69 .
  • Connor , T. H. , Theiss , J. C. , Hanna , H. A. , Monteith , D. K. and Matney , T. S. 1985 . Genotoxicity of organic chemicals frequently found in the air of mobile homes . Toxicol. Lett. , 25 : 33 – 40 .
  • Toiletry , Cosmetic and Association , Fragrance . 2005 . Calculation of margin of safety. Adult and baby exposures , Washington , DC : CTFA .
  • Crowell , P. L. , Lin , S. , Vedejs , E. and Gould , M. N. 1992 . Identification of metabolites of the antitumor agent d-limonene capable of inhibiting protein isoprenylation and cell growth . Cancer Chemother. Pharmacol. , 31 : 205 – 212 .
  • de Almeida , A. A. , Costa , J. P. , de Carvalho , R. B. , de Sousa , D. P. and de Freitas , R. M. 2012 . Evaluation of acute toxicity of a natural compound (+)-limonene epoxide and its anxiolytic-like action . Brain Res. , 1448 : 56 – 62 .
  • de Groot , A. C. and Frosch , P. J. 1997 . Adverse reactions to fragrances. A clinical review . Contact Derm. , 36 : 57 – 86 .
  • Desideri , P. , Lepri , L. and Checchini , L. 1991 . Organic compounds in seawater and pack ice in Terra Nova Bay (Antarctica) . Ann. Chim. , 81 : 395 – 416 .
  • Dietrich , D. R. and Swenberg , J. A. 1991 . The presence of α2u-globulin is necessary for d-limonene promotion of male rat kidney tumors . Cancer Res. , 51 : 3512 – 3521 .
  • Duetz , W. A. , Bouwmeester , H. , van Beilen , J. B. and Witholt , B. 2003 . Biotransformation of limonene by bacteria, fungi, yeasts, and plants . Appl. Microbiol. Biotechnol. , 61 : 269 – 277 .
  • European Commission. 2006. Opinion on the report “Emission of chemicals by air fresheners Tests on 74 consumer products sold in Europe” (BEUC report January 2005). Scientific Committee on Health and Environmental Risks (SCHER). http://ec.europa.eu/health/ph_risk/committees/04_scher/docs/scher_o_026.pdf (http://ec.europa.eu/health/ph_risk/committees/04_scher/docs/scher_o_026.pdf)
  • European Commission. 2010. Cosmetics directive. Council Directive 76/768/EEC. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CONSLEG:1976L0768:20100301:en:PDF (http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CONSLEG:1976L0768:20100301:en:PDF)
  • Evans , D. L. , Miller , D. M. , Jacobsen , K. L. and Bush , P. B. 1987 . Modulation of immune responses in mice by d–limonene . J. Toxicol. Environ. Health A , 20 : 51 – 66 .
  • Fahrig , R. 1984 . Genetic mode of action of cocarcinogens and tumor promoters in yeast and mice . Mol. Gen. Genet. , 194 : 7 – 14 .
  • Falk , A. , Fischer , T. and Hagberg , M. 1991 . Purpuric rash caused by dermal exposure to d–limonene . Contact Dermatitis , 25 : 198 – 199 .
  • Falk-Filipsson , A. , Löf , A. , Hagberg , M. , Hjelm , E. W. and Wang , Z. 1993 . d–Limonene exposure to humans by inhalation: Uptake, distribution, elimination, and effects on the pulmonary function . J. Toxicol. Environ. Health A , 38 : 77 – 88 .
  • Fehsenfeld , F. , Calvert , J. , Fall , R. , Goldan , P. , Guenther , A. B. , Hewitt , C. N. , Lamb , B. , Liu , S. , Trainer , M. and Westberg , H. 1992 . Emissions of volatile organic compounds from vegetation and the implications for atmospheric chemistry . Global Biogeochem. Cycle , 6 : 389 – 430 .
  • Flamm , W. G. and Lehman-McKeeman , L. D. 1991 . The human relevance of the renal tumor-inducing potential of d-limonene in male rats: Implications for risk assessment . Regul. Toxicol. Pharmacol. , 13 : 70 – 86 .
  • Flavor and Extract Manufacturers Association . 1991 . d-Limonene monograph , Washington , DC : FEMA .
  • Florin , I. , Rutberg , L. , Curvall , M. and Enzell , C. R. 1980 . Screening of tobacco smoke constituents for mutagenicity using the Ames test . Toxicology , 15 : 219 – 232 .
  • K , Friedrich , Delgado , I. F. , Santos , L. M. and Paumgartten , F. J. 2007 . Assessment of sensitization potential of monoterpenes using the rat popliteal lymph node assay . Food Chem. Toxicol. , 45 : 1516 – 1522 .
  • Gould , M. N. 1997 . Cancer chemoprevention and therapy by monoterpenes . Environ. Health Perspect. , 105 : 977 – 979 .
  • Greif , N. 1967 . Cutaneous safety of fragrance material as measured by the maximization test . Am. Perfume Cosmet. , 82 : 54 – 57 .
  • Hard , G. C. and Whysner , J. 1994 . Risk assessment of d-limonene: An example of male rat-specific renal tumorigens . Crit. Rev. Toxicol. , 24 : 231 – 254 .
  • Haworth , S. , Lawlor , T. , Mortelmans , K. , Speck , W. and Zeiger , E. 1983 . Salmonella mutagenicity test results for 250 chemicals . Environ. Mutagen. , 5 : 3 – 49 .
  • Health Canada. 2011. Cosmetic ingredient hotlist. (accessed April 7, 2012) http://www.hc-sc.gc.ca/cps-spc/cosmet-person/indust/hot-list-critique/hotlist-liste-eng.php (http://www.hc-sc.gc.ca/cps-spc/cosmet-person/indust/hot-list-critique/hotlist-liste-eng.php)
  • Helmig , D. and Arey , J. 1992 . Organic chemicals in the air at Whitaker's Forest/Sierra Nevada Mountains, California . Sci. Total Environ. , 112 : 233 – 250 .
  • Hutte , R. S. , Williams , E. J. , Staehelin , J. , Hawthorne , S. B. , Barkley , R. M. and Sievers , R. E. 1984 . Chromatographic analysis of organic compounds in the atmosphere . J. Chromatogr. , 302 : 173 – 179 .
  • IARC (International Agency for Research on Cancer). 1999. d-Limonene. IARC Monogr. Eval. Carcinogen. Risk Hum. 73: 307–327. http://monographs.iarc.fr/ENG/Monographs/vol73/mono73-16.pdf (http://monographs.iarc.fr/ENG/Monographs/vol73/mono73-16.pdf)
  • Igimi , H. , Nishimura , M. , Kodama , R. and Ide , H. 1974 . Studies on the metabolism of d-limonene (p-mentha-1,8-diene): I. The absorption, distribution and excretion of d-limonene in rats . Xenobiotica , 4 : 77 – 84 .
  • Igimi , H. , Hisatsugu , T. and Nishimura , M. 1976 . The use of d-limonene preparation as a dissolving agent of gallstones. Am. J . Dig. Dis. , 21 : 926 – 939 .
  • Igimi , H. , Tamura , R. , Toraishi , K. , Yamamoto , F. , Kataoka , A. , Ikejiri , Y. , Hisatsugu , T. and Shimura , H. 1991 . Medical dissolution of gallstones . Dig. Dis. Sci. , 36 : 200 – 208 .
  • International Programme on Chemical Safety . 1994 . Assessing health risks of chemicals: Derivation of guidance values for health-based exposure limits , Geneva , Switzerland : World Health Organization .
  • International Programme on Chemical Safety. 2005. d-Limonene. (accessed March 19, 2012) http://www.inchem.org/documents/icsc/icsc/eics0918.htm (http://www.inchem.org/documents/icsc/icsc/eics0918.htm)
  • Japan Ministry of Health, Labor, and Welfare. 2000. Standards for cosmetics. Ministry of Health and Welfare Notification No. 331. http://www.mhlw.go.jp/english/dl/cosmetics.pdf (http://www.mhlw.go.jp/english/dl/cosmetics.pdf)
  • Jüttner , F. 1988 . Quantitative analysis of monoterpenes and volatile organic pollution products (VOC) in forest air of the southern black forest . Chemosphere , 17 : 309 – 317 .
  • Kanerva , R. L. , Ridder , G. M. , Lefever , F. R. and Alden , C. L. 1987 . Comparison of short-term renal effects due to oral administration of decalin or d-limonene in young adult male Fischer-344 rats . Food Chem. Toxicol. , 25 : 345 – 353 .
  • Karlberg , A. T. , Boman , A. and Melin , B. 1991 . Animal experiments on the allergenicity of d-limonene—The citrus solvent . Ann. Occup. Hyg. , 35 : 419 – 426 .
  • Kim , H. , Barkey , B. and Paulson , S. E. 2012 . Real refractive indices and formation yields of secondary organic aerosol generated from photooxidation of limonene and α-pinene: The effect of the HC/NO(x) ratio . J. Phys. Chem. A , 116 : 6059 – 6067 .
  • Klecak , G. , Geleick , H. and Frey , J. 1977 . Screening of fragrance materials for allergenicity in the guinea pig. I. Comparison of four testing methods . J. Soc. Cosmet. Chem. , 28 : 53 – 64 .
  • Kodama , R. , Yano , T. , Furukawa , K. , Noda , K. and Ide , H. 1976 . Studies on the metabolism of d-limonene (p-mentha-1,8-diene). IV. Isolation and characterization of new metabolites and species differences in metabolism . Xenobiotica , 6 : 377 – 389 .
  • Kodama , R. , Okubo , A. , Araki , E. , Noda , K. , Ide , H. and Ikeda , T. 1977a . Studies on d-limonene as a gallstone solubilizer (VII): Effects on development of mouse fetuses and offspring . Oyo Yakuri , 13 : 863 – 873 .
  • Kodama , R. , Okubo , A. , Sato , K. , Araki , E. , Noda , K. , Ide , H. and Ikeda , T. 1977b . Studies on d-limonene as a gallstone solubilizer (IX).effects on development of rabbit fetuses and offspring . Oyo Yakuri , 13 : 885 – 898 .
  • Korea Food and Drug Administration. 2010. Provisions for designation of cosmetic ingredients. KFDA notification no. 2010–99. http://www.kfda.go.kr/index.kfda?x=0&searchkey=title:contents&mid=92&searchword=%C8%AD%C0%E5%C7%B0&y=0&division=&pageNo=1&seq=3401&cmd=v (http://www.kfda.go.kr/index.kfda?x=0&searchkey=title:contents&mid=92&searchword=%C8%AD%C0%E5%C7%B0&y=0&division=&pageNo=1&seq=3401&cmd=v)
  • Kyoto Encyclopedia of Genes and Genome. 2012. Limonene and pinene degradation. (accessed July 26, 2012) http://www.genome.jp/kegg-bin/show_pathway?map00903 (http://www.genome.jp/kegg-bin/show_pathway?map00903)
  • Larsen , S. T. , Hougaard , K. S. , Hammer , M. , Alarie , Y. , Wolkoff , P. , Clausen , P. A. , Wilkins , C. K. and Nielsen , G. D. 2000 . Effects of R-(+)- and S-(–)-limonene on the respiratory tract in mice . Hum. Exp. Toxicol. , 19 : 457 – 466 .
  • Lehman-McKeeman , L. D. and Caudill , D. 1992 . Biochemical basis for mouse resistance to hyaline droplet nephropathy: Lack of relevance of the alpha 2u-globulin protein superfamily in this male rat-specific syndrome . Toxicol. Appl. Pharmacol. , 112 : 214 – 221 .
  • Lehman-McKeeman , L. D. , Rodriguez , M. I. and Caudill , D. 1990 . Lysosomal degradation of alpha2μ-globulin and alpha2μ-globulin-xenobiotic conjugates . Toxicol. Appl. Pharmacol. , 103 : 539 – 548 .
  • Maisey , J. and Miller , K. 1986 . Assessment of the ability of mice fed on vitamin A supplemented diet to respond to a variety of potential contact sensitizers . Contact Dermatitis , 15 : 17 – 23 .
  • Maksymiuk , C. S. , Gayahtri , C. , Gil , R. R. and Donahue , N. M. 2009 . Secondary organic aerosol formation from multiphase oxidation of limonene by ozone: Mechanistic constraints via two-dimensional heteronuclear NMR spectroscopy . Phys. Chem. Chem. Phys. , 11 : 7810 – 7818 .
  • Matura , M. , Goossens , A. , Bordalo , O. , Garcia-Bravo , B. , Magnusson , K. , Wrangsjö , K. and Karlberg , A. T. 2002 . Oxidized citrus oil (R-limonene): A frequent skin sensitizer in Europe . J. Am. Acad. Dermatol. , 47 : 709 – 714 .
  • Matura , M. , Goossens , A. , Bordalo , O. , Garcia-Bravo , B. , Magnusson , K. , Wrangsjö , K. and Karlberg , A. T. 2003 . Patch testing with oxidized R-(+)-limonene and its hydroperoxide fraction . Contact Dermatitis , 49 : 15 – 21 .
  • Matura , M. , Sköld , M. , Börje , A. , Andersen , K. E. , Bruze , M. , Frosch , P. , Goossens , A. , Johansen , J. D. , Svedman , C. , White , I. R. and Karlberg , A. T. 2006 . Not only oxidized R-(+)- but also S-(–)-limonene is a common cause of contact allergy in dermatitis patients in Europe . Contact Dermatits , 55 : 274 – 279 .
  • McCreary , J. J. , Jackson , J. A. G. and Zoltek , J. Jr . 1983 . Toxic chemicals in an abandoned phenolic waste site . Chemosphere , 12 : 1619 – 1632 .
  • National Board of Occupational Safety and Health . 1993 . Occupational exposure limit value , Vol. 3 , Ordinance AFS .
  • National Institute for Occupational Safety and Health. 2005. d-Limonene. (accessed August 5, 2012) http://www.cdc.gov/niosh/ipcsneng/neng0918.html (http://www.cdc.gov/niosh/ipcsneng/neng0918.html)
  • National Toxicology Program. 1990. Toxicology and carcinogenesis studies of d-limonene in F344/N rats and B6C3F1 mice. NTP TR 347, 1–165. http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr347.pdf (http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr347.pdf)
  • Nilsson , U. , Magnusson , K. , Karlberg , O. and Karlberg , A. T. 1999 . Are contact allergens stable in patch test preparations? Investigation of the degradation of d–limonene hydroperoxides in petrolatum . Contact Dermatitis , 40 : 127 – 132 .
  • Nøjgaard , J. K. , Christensen , K. B. and Wolkoff , P. 2005 . The effect on human eye blink frequency of exposure to limonene oxidation products and methacrolein . Toxicol. Lett. , 156 : 241 – 251 .
  • Okabe , H. , Obata , Y. , Takayama , K. and Nagai , T. 1990 . Percutaneous absorption enhancing effect and skin irritation of monocyclic monoterpenes . Drug Design Deliv. , 6 : 229 – 238 .
  • Olson , M. J. , Johnson , J. T. and Reidy , C. A. 1990 . A comparison of male rat and human urinary proteins: Implications for human resistance to hyaline droplet nephropathy . Toxicol. Appl. Pharmacol. , 102 : 524 – 536 .
  • Opdyke , D. L. 1979 . Monographs on fragrance raw materials . Food Cosmet. Toxicol. , 17 : 241 – 275 .
  • Oshiro , Y. , Balwierz , P. S. , Eurell , T. E. , Morris , D. L. and Alden , C. L.. 1998 . Exploration of the transformation potential of a unique male rat protein alpha2u-globulin using hamster embryonic cells . Toxicol. Pathol. , 26 : 381 – 387 .
  • Pellizzari , E. D. , Hartwell , T. D. , Harris , B. S. H. , Waddell , R. D. , Whitaker , D. A. and Erickson , M. D. 1982 . Purgeable organic compounds in mother's milk . Bull. Environ. Contam.Toxicol. , 28 : 322 – 328 .
  • Pienta , R. 1980 . Evaluation and relevance of the Syrian hamster embryo cell system . Appl. Met. Oncol. , 3 : 149 – 169 .
  • Poon , G. , Vigushin , D. , Griggs , L. , Rowlands , M. , Coombes , R. and Jarman , M. 1996 . Identification and characterization of limonene metabolites in patients with advanced cancer by liquid chromatography/mass spectrometry . Drug Metab. Dispos , 24 : 565 – 571 .
  • Rabi , T. and Bishayee , A. 2009 . d-limonene sensitizes docetaxel-induced cytotoxicity in human prostate cancer cells: Generation of reactive oxygen species and induction of apoptosis . J. Carcinogen. , 8 : 1 – 9 .
  • Roberts , J. M. , Hahn , C. J. , Fehsenfeld , F. C. , Warnock , J. M. , Albritton , D. L. and Sievers , R. E. 1985 . Monoterpene hydrocarbons in the nighttime troposphere . Environ. Sci. Technol. , 19 : 364 – 369 .
  • Rolseth , V. , Djurhuus , R. and Svardal , A. M. 2002 . Additive toxicity of limonene and 50% oxygen and the role of glutathione in detoxification in human lung cells . Toxicology , 170 : 75 – 88 .
  • Rycroft , R. J. G. 1980 . Allergic contact dermatitis from dipentene in honing oil . Contact Dermat. , 6 : 325 – 329 .
  • Sauer , T. C. 1981 . Volatile organic compounds in open ocean and coastal surface waters . Org. Geochem. , 3 : 91 – 101 .
  • Schäfer , R. and Schäfer , W. 1982 . Die perkutaneresorptionverschiedener Terpene–Menthol, campher, limonen, isobornylacetat, α-Pinen–ausbadezusätzen . Arzneim. Forsch. , 32 : 56 – 58 .
  • Shaw , R. W. , Crittenden , A. L. , Stevens , R. K. , Cronn , D. R. and Titov , V. S. 1983 . Ambient concentrations of hydrocarbons from conifers in atmospheric gases and aerosol particles measured in soviet Georgia . Environ. Sci. Technol. , 17 : 389 – 395 .
  • Singal , M. , Vitale , D. and Smith , L. 2011 . Fragranced products and VOCs . Environ. Health Perspect. , 119 : A200
  • Steele , V. E. , Kelloff , G. J. , Wilkinson , B. P. and Arnold , J. T. 1990 . Inhibition of transformation in cultured rat tracheal epithelial cells by potential chemopreventive agents . Cancer Res. , 50 : 2068 – 2074 .
  • Strömvall, A. M. 1992. Terpenes emitted to air from forestry and the forest industry. Göteborg, Sweden: Chalmers University of Technology. http://publications.lib.chalmers.se/records/fulltext/1519.pdf (http://publications.lib.chalmers.se/records/fulltext/1519.pdf)
  • Sun , J. 2007 . d-Limonene: Safety and clinical applications . Altern. Med. Rev. , 12 : 259 – 264 .
  • Tsuji , M. , Fujisaki , Y. , Yamachika , K. , Nakagami , K. , Fujisaka , F. , Mito , M. , Aoki , T. , Kinoshita , S. , Okubo , A. and Watanabe , I. 1974 . Studies on d-limonene, as gallstone solubilizer (I): General pharmacological studies . Oyo Yakuri , 8 : 1439 – 1459 .
  • Tsuji , M. , Fujisaki , Y. , Okubo , A. , Arikawa , Y. , Noda , K. , Ide , H. and Ikeda , T. 1975a . Studies on d-limonene, as gallstone solubilizer (V): Effects on development of rat fetuses and offspring . Oyo Yakuri , 9 : 179 – 186 .
  • Tsuji , M. , Fujisaki , Y. , Arikawa , K. , Masuda , S. , Tanaka , T. , Sato , K. , Noda , K. , Ide , H. and Kikuchi , M. 1975b . Studies on d-limonene, as gallstone solubilizer (IV): Chronic toxicity in dogs . Oyo Yakuri , 9 : 775 – 808 .
  • U.S. Environmental Protection Agency. 1994. Limonene. EPA-738-F-94-030, 1–5. http://www.epa.gov/oppsrrd1/REDs/factsheets/3083fact.pdf (http://www.epa.gov/oppsrrd1/REDs/factsheets/3083fact.pdf)
  • U.S. Environmental Protection Agency. 2004. Exposure and risk assessment on lower risk pesticide chemicals; d-Limonene. Arlington, VA: Office of Pesticide Programs. http://www.epa.gov/oppsrrd1/REDs/limonene_tred.pdf (http://www.epa.gov/oppsrrd1/REDs/limonene_tred.pdf)
  • U.S. Food and Drug Administration. 2011. Synthetic flavoring substances and adjuvants. 21 CFR §182.60. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=182.60 (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=182.60)
  • U.S. Food and Drug Administration. 2012. General. 21 CFR §700. http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?c=ecfr&sid=89cf1d1eb4f13f6dd2564e0158a77d48&rgn=div5&view=text&node=21:7.0.1.2.10&idno=21 (http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?c=ecfr&sid=89cf1d1eb4f13f6dd2564e0158a77d48&rgn=div5&view=text&node=21:7.0.1.2.10&idno=21)
  • U.S. National Oceanic and Atmospheric Administration. 1992. d-Limonene. (accessed March 19, 2012) http://cameochemicals.noaa.gov/chemical/20568 (http://cameochemicals.noaa.gov/chemical/20568)
  • van der Werf , M. , de Bont , J. and Leak , D. 1997 . Opportunities in microbial biotransformation of monoterpenes . Adv. Biochem. Eng. Biotechnol. , 55 : 147 – 177 .
  • Vigushin , D. M. , Poon , G. K. , Boddy , A. , English , J. , Halbert , G. W. , Pagonis , C. , Jarman , M. and Coombes , R. C. 1998 . Phase I and pharmacokinetic study of d-limonene in patients with advanced cancer . Cancer Chemother. Pharmacol. , 42 : 111 – 117 .
  • Wallace , L. , Nelson , W. , Ziegenfus , R. , Pellizzari , E. , Michael , L. , Whitmore , R. , Zelon , H. , Hartwell , T. , Perritt , R. and Westerdahl , D. 1991 . The Los Angeles TEAM study: Personal exposures, indoor–outdoor air concentrations, and breath concentrations of 25 volatile organic compounds . J. Expos. Anal. Environ. Epidemiol. , 1 : 157 – 192 .
  • Walser , M. L. , Park , J. , Gomez , A. L. , Russell , A. R. and Nizkorodov , S. A. 2007 . Photochemical aging of secondary organic aerosol particles generated from the oxidation of d-limonene . J. Phys. Chem. A , 111 : 1907 – 1913 .
  • Watabe , T. , Hiratsuka , A. , Ozawa , N. and Isobe , M. 1981 . A comparative study on the metabolism of d-limonene and 4-vinylcyclohex-1-ene by hepatic microsomes . Xenobiotica , 11 : 333 – 344 .
  • Webb , D. , Ridder , G. and Alden , C. 1989 . Acute and subchronic nephrotoxicity of d-limonene in Fischer 344 rats . Food. Chem. Toxicol. , 27 : 639 – 649 .
  • Webb , D. , Kanerva , R. , Hysell , D. , Alden , C. and Lehman-McKeeman , L. 1990 . Assessment of the subchronic oral toxicity of d-limonene in dogs . Food. Chem. Toxicol. , 28 : 669 – 675 .
  • Whysner , J. and Williams , G. M. 1996 . d-limonene mechanistic data and risk assessment: Absolute species-specific cytotoxicity, enhanced cell proliferation, and tumor promotion . Pharmacol Ther. , 71 : 127 – 136 .
  • Wolkoff , P. , Clausen , P. A. , Larsen , K. , Hammer , M. , Larsen , S. T. and Nielsen , G. D. 2008 . Acute airway effects of ozone-initiated d-limonene chemistry: importance of gaseous products . Toxicol Lett. , 181 : 171 – 176 .
  • World Health Organization. 1998. Concise international chemical assessment document 5. Limonene. Geneva, Switzerland: International Programme on Chemical Safety, WHO. http://whqlibdoc.who.int/publications/1998/9241530057.pdf (http://whqlibdoc.who.int/publications/1998/9241530057.pdf)
  • Yoon , W. J. , Lee , N. H. and Hyun , C. G. 2010 . Limonene suppresses lipopolysaccharide-induced production of nitric oxide, prostaglandin E 2, and pro-inflammatory cytokines in RAW 264.7 macrophages . J. Oleo Sci. , 59 : 415 – 421 .
  • York , M. , Basketter , D. , Cuthbert , J. and Neilson , L. 1995 . Skin irritation testing in man for hazard assessment—Evaluation of four patch systems . Hum. Exp. Toxicol. , 14 : 729 – 734 .
  • Zhou , W. , Yoshioka , M. and Yokogoshi , H. 2009 . Sub-chronic effects of s-limonene on brain neurotransmitter levels and behavior of rats . J. Nutr. Sci. Vitaminol. (Tokyo) , 55 : 367 – 373 .

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.