Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

General Review Article

Considering a Potential Role of Linalool as a Mood Stabilizer for Bipolar Disorder

Author(s): Kate Levenberg*, Wade Edris, Martha Levine and Daniel R. George

Volume 26 , Issue 40 , 2020

Page: [5128 - 5133] Pages: 6

DOI: 10.2174/1381612826666200724160742

Price: $65

Abstract

Epidemiologic studies suggest that the lifetime prevalence of bipolar spectrum disorders ranges from 2.8 to 6.5 percent of the population. To decrease morbidity and mortality associated with disease progression, pharmacologic intervention is indicated for the majority of these patients. While a number of effective treatment regimens exist, many conventional medications have significant side effect profiles that adversely impact patients’ short and long-term well-being. It is thus important to continue advancing and improving therapeutic options available to patients. This paper reviews the limitations of current treatments and examines the chemical compound Linalool, an alcohol found in many plant species, that may serve as an effective mood stabilizer. While relatively little is known about Linalool and bipolar disorder, the compound has been shown to have antiepileptic, anti-inflammatory, anxiolytic, anti-depressive, and neurotrophic effects, with mechanisms that are comparable to current bipolar disorder treatment options.

Keywords: Bipolar disorder, Linalool, neurotherapeutics, anti-epileptic, drug development, plant-based medicine.

[1]
[2]
Purcell SM, Wray NR, Stone JL, et al. International Schizophrenia Consortium. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009; 460(7256): 748-52.
[http://dx.doi.org/10.1038/nature08185] [PMID: 19571811]
[3]
Angst J. The bipolar spectrum. Br J Psychiatry 2007; 190(3): 189-91.
[http://dx.doi.org/10.1192/bjp.bp.106.030957] [PMID: 17329735]
[4]
Hamlat EJ, Garro-Moore JKO, Nusslock R, Alloy LB. Assessment and treatment of bipolar spectrum disorders in emerging adulthood: applying the behavioral approach system hypersensitivity model. Cognit Behav Pract 2016; 23(3): 289-99.
[http://dx.doi.org/10.1016/j.cbpra.2016.05.001] [PMID: 28133431]
[5]
Bourne C, Aydemir Ö, Balanzá-Martínez V, et al. Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis. Acta Psychiatr Scand 2013; 128(3): 149-62.
[http://dx.doi.org/10.1111/acps.12133] [PMID: 23617548]
[6]
Kurtz MM, Gerraty RT. A meta-analytic investigation of neurocognitive deficits in bipolar illness: profile and effects of clinical state. Neuropsychology 2009; 23(5): 551-62.
[http://dx.doi.org/10.1037/a0016277] [PMID: 19702409]
[7]
Solé B, Jiménez E, Torrent C, et al. Cognitive impairment in bipolar disorder: treatment and prevention strategies. Int J Neuropsychopharmacol 2017; 20(8): 670-80.
[http://dx.doi.org/10.1093/ijnp/pyx032] [PMID: 28498954]
[8]
Scott J, Pope M. Nonadherence with mood stabilizers: prevalence and predictors. J Clin Psychiatry 2002; 63(5): 384-90.
[http://dx.doi.org/10.4088/JCP.v63n0502] [PMID: 12019661]
[9]
Fleck DE, Keck PE Jr, Corey KB, Strakowski SM. Factors associated with medication adherence in African American and white patients with bipolar disorder. J Clin Psychiatry 2005; 66(5): 646-52.
[http://dx.doi.org/10.4088/JCP.v66n0517] [PMID: 15889954]
[10]
Sajatovic M, Valenstein M, Blow FC, Ganoczy D, Ignacio RV. Treatment adherence with antipsychotic medications in bipolar disorder. Bipolar Disord 2006; 8(3): 232-41.
[http://dx.doi.org/10.1111/j.1399-5618.2006.00314.x] [PMID: 16696824]
[11]
James Lake MD. Integrative treatment of bipolar disorder: a review of the evidence and recommendations. Psychiatric Times 2013. Available fom: https://www.psychiatrictimes.com/integrative-treatment-bipolar-disorder-review-evidence-and-recommendations
[12]
Elkins G, Rajab MH, Marcus J. Complementary and alternative medicine use by psychiatric inpatients. Psychol Rep 2005; 96(1): 163-6.
[http://dx.doi.org/10.2466/pr0.96.1.163-166] [PMID: 15825920]
[13]
Manji HK, Bowden CL, Belmaker RH. Bipolar medications: mechanisms of action. J Nerv Ment Dis 2001; 189: 64-5.
[14]
Hedya SA, Swoboda HD. Lithium Toxicity StatPearls. Treasure Island, FL: StatPearls Publishing 2019. Available from: http://www.ncbi.nlm.nih.gov/books/NBK499992/
[15]
Licht RW. Lithium: still a major option in the management of bipolar disorder. CNS Neurosci Ther 2012; 18(3): 219-26.
[http://dx.doi.org/10.1111/j.1755-5949.2011.00260.x] [PMID: 22070642]
[16]
Bauer M, Blumentritt H, Finke R, et al. Using ultrasonography to determine thyroid size and prevalence of goiter in lithium-treated patients with affective disorders. J Affect Disord 2007; 104(1-3): 45-51.
[http://dx.doi.org/10.1016/j.jad.2007.01.033] [PMID: 17346802]
[17]
Murru A, Popovic D, Pacchiarotti I, Hidalgo D, León-Caballero J, Vieta E. Management of adverse effects of mood stabilizers. Curr Psychiatry Rep 2015; 17(8): 603.
[http://dx.doi.org/10.1007/s11920-015-0603-z] [PMID: 26084665]
[18]
Tredget J, Kirov A, Kirov G. Effects of chronic lithium treatment on renal function. J Affect Disord 2010; 126(3): 436-40.
[http://dx.doi.org/10.1016/j.jad.2010.04.018] [PMID: 20483164]
[19]
Aiff H, Attman P-O, Aurell M, et al. Effects of 10 to 30 years of lithium treatment on kidney function. J Psychopharmacol (Oxford) 2015; 29(5): 608-14.
[http://dx.doi.org/10.1177/0269881115573808] [PMID: 25735990]
[20]
Meador KJ, Loring DW, Huh K, Gallagher BB, King DW. Comparative cognitive effects of anticonvulsants. Neurology 1990; 40(3 Pt 1): 391-4.
[http://dx.doi.org/10.1212/WNL.40.3_Part_1.391] [PMID: 2314578]
[21]
Fagiolini A, Chengappa KNR, Soreca I, Chang J. Bipolar disorder and the metabolic syndrome: causal factors, psychiatric outcomes and economic burden. CNS Drugs 2008; 22(8): 655-69.
[http://dx.doi.org/10.2165/00023210-200822080-00004] [PMID: 18601304]
[22]
La Torre A, Giupponi G, Duffy D, Conca A, Catanzariti D. Sexual dysfunction related to drugs: a critical review. Part IV: cardiovascular drugs. Pharmacopsychiatry 2015; 48(1): 1-6.
[PMID: 25405774]
[23]
Kaufman KR, Coluccio M, Sivaraaman K, Campeas M. Lamotrigine-induced sexual dysfunction and non-adherence: case analysis with literature review. BJPsych Open 2017; 3(5): 249-53.
[http://dx.doi.org/10.1192/bjpo.bp.117.005538] [PMID: 29034101]
[24]
Nasreddine W, Beydoun A. Valproate-induced thrombocytopenia: a prospective monotherapy study. Epilepsia 2008; 49(3): 438-45.
[http://dx.doi.org/10.1111/j.1528-1167.2007.01429.x] [PMID: 18031547]
[25]
Lenox RH, McNamara RK, Papke RL, Manji HK. Neurobiology of lithium: an update. J Clin Psychiatry 1998; 59(Suppl. 6): 37-47.
[PMID: 9674936]
[26]
Chazot G, Gogoleva IV, Gromova OA, Ullubiev NM, Nikonov AA. Neurobiology of lithium. Zh Nevrol Psikhiatr Im S S Korsakova 2008; (Suppl. 22)49-55.
[PMID: 19425290]
[27]
Berridge MJ, Downes CP, Hanley MR. Neural and developmental actions of lithium: a unifying hypothesis. Cell 1989; 59(3): 411-9.
[http://dx.doi.org/10.1016/0092-8674(89)90026-3] [PMID: 2553271]
[28]
Chang MCJ, Grange E, Rabin O, Bell JM, Allen DD, Rapoport SI. Lithium decreases turnover of arachidonate in several brain phospholipids. Neurosci Lett 1996; 220(3): 171-4.
[http://dx.doi.org/10.1016/S0304-3940(96)13264-X] [PMID: 8994220]
[29]
Rintala J, Seemann R, Chandrasekaran K, et al. 85 kDa cytosolic phospholipase A2 is a target for chronic lithium in rat brain. Neuroreport 1999; 10(18): 3887-90.
[http://dx.doi.org/10.1097/00001756-199912160-00030] [PMID: 10716228]
[30]
Rao JS, Lee H-J, Rapoport SI, Bazinet RP. Mode of action of mood stabilizers: is the arachidonic acid cascade a common target? Mol Psychiatry 2008; 13(6): 585-96.
[http://dx.doi.org/10.1038/mp.2008.31] [PMID: 18347600]
[31]
Bowden CL, Calabrese JR, Sachs G, et al. Lamictal 606 Study Group. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder. Arch Gen Psychiatry 2003; 60(4): 392-400.
[http://dx.doi.org/10.1001/archpsyc.60.4.392] [PMID: 12695317]
[32]
Calabrese JR, Bowden CL, Sachs G, et al. Lamictal 605 Study Group. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. J Clin Psychiatry 2003; 64(9): 1013-24.
[http://dx.doi.org/10.4088/JCP.v64n0906] [PMID: 14628976]
[33]
Terence AK. Potential mechanisms of action of lamotrigine in the treatment of bipolar disorders. J Clin Psychopharmacol 2003; 23(5): 484-95.
[34]
Lee H-J, Rao JS, Chang L, Rapoport SI, Bazinet RP. Chronic lamotrigine does not alter the turnover of arachidonic acid within brain phospholipids of the unanesthetized rat: implications for the treatment of bipolar disorder. Psychopharmacology (Berl) 2007; 193(4): 467-74.
[http://dx.doi.org/10.1007/s00213-007-0803-2] [PMID: 17487474]
[35]
Li N, He X, Zhang Y, et al. Brain-derived neurotrophic factor signalling mediates antidepressant effects of lamotrigine. Int J Neuropsychopharmacol 2011; 14(8): 1091-8.
[http://dx.doi.org/10.1017/S1461145710001082] [PMID: 20846461]
[36]
Davies JA. Mechanisms of action of antiepileptic drugs 1995; 5
[http://dx.doi.org/10.1016/S1059-1311(95)80003-4]
[37]
Bosetti F, Weerasinghe GR, Rosenberger TA, Rapoport SI. Valproic acid down-regulates the conversion of arachidonic acid to eicosanoids via cyclooxygenase-1 and -2 in rat brain. J Neurochem 2003; 85(3): 690-6.
[http://dx.doi.org/10.1046/j.1471-4159.2003.01701.x] [PMID: 12694395]
[38]
Bazinet RP, Rao JS, Chang L, Rapoport SI, Lee H-J. Chronic carbamazepine decreases the incorporation rate and turnover of arachidonic acid but not docosahexaenoic acid in brain phospholipids of the unanesthetized rat: relevance to bipolar disorder. Biol Psychiatry 2006; 59(5): 401-7.
[http://dx.doi.org/10.1016/j.biopsych.2005.07.024] [PMID: 16182257]
[39]
Ghelardoni S, Tomita YA, Bell JM, Rapoport SI, Bosetti F. Chronic carbamazepine selectively downregulates cytosolic phospholipase A2 expression and cyclooxygenase activity in rat brain. Biol Psychiatry 2004; 56(4): 248-54.
[http://dx.doi.org/10.1016/j.biopsych.2004.05.012] [PMID: 15312812]
[40]
Nishino S, Ohtomo K, Numata Y, Sato T, Nakahata N, Kurita M. Divergent effects of lithium and sodium valproate on brain-derived neurotrophic factor (BDNF) production in human astrocytoma cells at therapeutic concentrations. Prog Neuropsychopharmacol Biol Psychiatry 2012; 39(1): 17-22.
[http://dx.doi.org/10.1016/j.pnpbp.2011.07.008] [PMID: 21803112]
[41]
Peana AT, Rubattu P, Piga GG, et al. Involvement of adenosine A1 and A2A receptors in (-)-linalool-induced antinociception. Life Sci 2006; 78(21): 2471-4.
[http://dx.doi.org/10.1016/j.lfs.2005.10.025] [PMID: 16343551]
[42]
Elisabetsky E, Marschner J, Souza DO. Effects of Linalool on glutamatergic system in the rat cerebral cortex. Neurochem Res 1995; 20(4): 461-5.
[http://dx.doi.org/10.1007/BF00973103] [PMID: 7651584]
[43]
Harvey AG, Talbot LS, Gershon A. Sleep disturbance in bipolar disorder across the lifespan. Clin Psychol (New York) 2009; 16(2): 256-77.
[http://dx.doi.org/10.1111/j.1468-2850.2009.01164.x] [PMID: 22493520]
[44]
Petiwala SM, Puthenveetil AG, Johnson JJ. Polyphenols from the Mediterranean herb rosemary (Rosmarinus officinalis) for prostate cancer Front Pharmacol. 2013. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3607075/
[45]
Hajhashemi V, Ghannadi A, Sharif B. Anti-inflammatory and analgesic properties of the leaf extracts and essential oil of Lavandula angustifolia Mill. J Ethnopharmacol 2003; 89(1): 67-71.
[http://dx.doi.org/10.1016/S0378-8741(03)00234-4] [PMID: 14522434]
[46]
Cheng B-H, Sheen L-Y, Chang S-T. Evaluation of anxiolytic potency of essential oil and S-(+)-linalool from Cinnamomum osmophloeum ct. linalool leaves in mice. J Tradit Complement Med 2014; 5(1): 27-34.
[http://dx.doi.org/10.1016/j.jtcme.2014.10.007] [PMID: 26151006]
[47]
Guzmán-Gutiérrez SL, Gómez-Cansino R, García-Zebadúa JC, Jiménez-Pérez NC, Reyes-Chilpa R. Antidepressant activity of Litsea glaucescens essential oil: identification of β-pinene and linalool as active principles. J Ethnopharmacol 2012; 143(2): 673-9.
[http://dx.doi.org/10.1016/j.jep.2012.07.026] [PMID: 22867633]
[48]
Brum LFS, Elisabetsky E, Souza D. Effects of linalool on [(3)H]MK801 and [(3)H] muscimol binding in mouse cortical membranes. Phytother Res 2001; 15(5): 422-5.
[http://dx.doi.org/10.1002/ptr.973] [PMID: 11507735]
[49]
Elisabetsky E, Brum LF, Souza DO. Anticonvulsant properties of linalool in glutamate-related seizure models. Phytomedicine 1999; 6(2): 107-13.
[http://dx.doi.org/10.1016/S0944-7113(99)80044-0] [PMID: 10374249]
[50]
Shimada T, Yamagata K. Pentylenetetrazole-induced kindling mouse model. J Vis Exp 2018; 12(136)
[http://dx.doi.org/10.3791/56573] [PMID: 29985308]
[51]
Bender RE, Alloy LB. Life stress and kindling in bipolar disorder: review of the evidence and integration with emerging biopsychosocial theories. Clin Psychol Rev 2011; 31(3): 383-98.
[http://dx.doi.org/10.1016/j.cpr.2011.01.004] [PMID: 21334286]
[52]
Ghaemi SN, Boiman EE, Goodwin FK. Kindling and second messengers: an approach to the neurobiology of recurrence in bipolar disorder. Biol Psychiatry 1999; 45(2): 137-44.
[http://dx.doi.org/10.1016/S0006-3223(98)00256-X] [PMID: 9951560]
[53]
Subramanian K, Sarkar S, Kattimani S, Philip Rajkumar R, Penchilaiya V. Role of stressful life events and kindling in bipolar disorder: Converging evidence from a mania-predominant illness course. Psychiatry Res 2017; 258: 434-7.
[http://dx.doi.org/10.1016/j.psychres.2017.08.073] [PMID: 28870645]
[54]
Meador KJ, Baker GA. Behavioral and cognitive effects of lamotrigine. J Child Neurol 1997; 12(1): S44-7.
[55]
Cunningham MO, Jones RSG. The anticonvulsant, lamotrigine decreases spontaneous glutamate release but increases spontaneous GABA release in the rat entorhinal cortex in vitro. Neuropharmacology 2000; 39(11): 2139-46.
[http://dx.doi.org/10.1016/S0028-3908(00)00051-4] [PMID: 10963757]
[56]
Peana AT, D’Aquila PS, Panin F, Serra G, Pippia P, Moretti MDL. Anti-inflammatory activity of linalool and linalyl acetate constituents of essential oils. Phytomedicine 2002; 9(8): 721-6.
[http://dx.doi.org/10.1078/094471102321621322] [PMID: 12587692]
[57]
Huo M, Cui X, Xue J, et al. Anti-inflammatory effects of linalool in RAW 264.7 macrophages and lipopolysaccharide-induced lung injury model. J Surg Res 2013; 180(1): e47-54.
[http://dx.doi.org/10.1016/j.jss.2012.10.050] [PMID: 23228323]
[58]
Li J, Zhang X, Huang H. Protective effect of linalool against lipopolysaccharide/D-galactosamine-induced liver injury in mice. Int Immunopharmacol 2014; 23(2): 523-9.
[http://dx.doi.org/10.1016/j.intimp.2014.10.001] [PMID: 25311666]
[59]
Sabogal-Guáqueta AM, Osorio E, Cardona-Gómez GP. Linalool reverses neuropathological and behavioral impairments in old triple transgenic Alzheimer’s mice. Neuropharmacology 2016; 102: 111-20.
[http://dx.doi.org/10.1016/j.neuropharm.2015.11.002] [PMID: 26549854]
[60]
Gunaseelan S, Balupillai A, Govindasamy K, et al. Linalool prevents oxidative stress activated protein kinases in single UVB-exposed human skin cells. PLoS One 2017; 12(5)e0176699
[http://dx.doi.org/10.1371/journal.pone.0176699] [PMID: 28467450]
[61]
Linck VM, da Silva AL, Figueiró M, Caramão EB, Moreno PRH, Elisabetsky E. Effects of inhaled linalool in anxiety, social interaction and aggressive behavior in mice. Phytomedicine 2010; 17(8-9): 679-83.
[http://dx.doi.org/10.1016/j.phymed.2009.10.002] [PMID: 19962290]
[62]
Umezu T, Nagano K, Ito H, Kosakai K, Sakaniwa M, Morita M TU. Anticonflict effects of lavender oil and identification of its active constituents. Pharmacol Biochem Behav 2006; 85(4): 713-21.
[http://dx.doi.org/10.1016/j.pbb.2006.10.026] [PMID: 17173962]
[63]
Caputo L, Reguilon MD, Mińarro J, De Feo V, Rodriguez-Arias M. Lavandula angustifolia essential oil and linalool counteract social aversion induced by social defeat. Molecules 2018; 23(10): 2694.
[http://dx.doi.org/10.3390/molecules23102694] [PMID: 30347669]
[64]
Bianchini AE, Garlet QI, da Cunha JA, et al. Monoterpenoids (thymol, carvacrol and S-(+)-linalool) with anesthetic activity in silver catfish (Rhamdia quelen): evaluation of acetylcholinesterase and GABAergic activity Braz J Med Biol Res 2017. Available from: http://www.scielo.br/scielo.php?script=sci_abstract&pid=S0100-879X2017001200610&lng=en&nrm=iso&tlng=en
[65]
Höferl M, Krist S, Buchbauer G. Chirality influences the effects of linalool on physiological parameters of stress. Planta Med 2006; 72(13): 1188-92.
[http://dx.doi.org/10.1055/s-2006-947202] [PMID: 16983600]
[66]
Yamada K, Mimaki Y, Sashida Y. Effects of inhaling the vapor of Lavandula burnatii super-derived essential oil and linalool on plasma adrenocorticotropic hormone (ACTH), catecholamine and gonadotropin levels in experimental menopausal female rats. Biol Pharm Bull 2005; 28(2): 378-9.
[http://dx.doi.org/10.1248/bpb.28.378] [PMID: 15684505]
[67]
Yoshida K, Yamamoto N, Fujiwara S, Kamei A, Abe K, Nakamura A. Inhalation of a racemic mixture (R,S)-linalool by rats experiencing restraint stress alters neuropeptide and MHC class I gene expression in the hypothalamus. Neurosci Lett 2017; 653: 314-9.
[http://dx.doi.org/10. 1016/j.neulet.2017.05.046] [PMID: 28595953]
[68]
Daban C, Vieta E, Mackin P, Young AH. Hypothalamic-pituitary-adrenal axis and bipolar disorder. Psychiatr Clin North Am 2005; 28(2): 469-80.
[http://dx.doi.org/10.1016/j.psc.2005.01.005] [PMID: 15826743]
[69]
Guzmán-Gutiérrez SL, Bonilla-Jaime H, Gómez-Cansino R, Reyes-Chilpa R. Linalool and β-pinene exert their antidepressant-like activity through the monoaminergic pathway. Life Sci 2015; 128: 24-9.
[http://dx.doi.org/10.1016/j.lfs.2015.02.021] [PMID: 25771248]
[70]
Coelho V, Mazzardo-Martins L, Martins DF, et al. Neurobehavioral and genotoxic evaluation of (-)-linalool in mice. J Nat Med 2013; 67(4): 876-80.
[http://dx.doi.org/10.1007/s11418-013-0751-6] [PMID: 23436179]
[71]
Dos Santos ÉRQ, Maia CSF, Fontes E.A. Junior, Melo AS, Pinheiro BG, Maia JGS. Linalool-rich essential oils from the Amazon display antidepressant-type effect in rodents. J Ethnopharmacol 2018; 212: 43-9.
[http://dx.doi.org/10.1016/j.jep.2017.10.013] [PMID: 29037915]
[72]
Mehri S, Meshki MA, Hosseinzadeh H. Linalool as a neuroprotective agent against acrylamide-induced neurotoxicity in Wistar rats. Drug Chem Toxicol 2015; 38(2): 162-6.
[http://dx.doi.org/10.3109/01480545.2014.919585] [PMID: 24844946]
[73]
Alinejad B, Ghorbani A, Sadeghnia HR. Effects of combinations of curcumin, linalool, rutin, safranal, and thymoquinone on glucose/serum deprivation-induced cell death. Avicenna J Phytomed 2013; 3(4): 321-8.
[PMID: 25050289]
[74]
Sabogal-Guáqueta AM, Posada-Duque R, Cortes NC, Arias-Londoño JD, Cardona-Gómez GP. Changes in the hippocampal and peripheral phospholipid profiles are associated with neurodegeneration hallmarks in a long-term global cerebral ischemia model: Attenuation by Linalool. Neuropharmacology 2018; 135: 555-71.
[http://dx.doi.org/10.1016/j.neuropharm.2018.04.015] [PMID: 29680773]
[75]
Sugawara Y, Shigetho A, Yoneda M, Tuchiya T, Matumura T, Hirano M. Relationship between mood change, odour and its physiological effects in humans while inhaling the fragrances of essential oils as well as linalool and its enantiomers. Molecules 2013; 18(3): 3312-38.
[http://dx.doi.org/10.3390/molecules18033312] [PMID: 23486108]
[76]
Hosseinzadeh S, Jafarikukhdan A, Hosseini A, Armand R. The application of medicinal plants in traditional and modern medicine: a review of thymus vulgaris. Int J Clin Med 2015; 06(09): 635-42.
[http://dx.doi.org/10.4236/ijcm.2015.69084]
[77]
Kohn R, Saxena S, Levav I, Saraceno B. The treatment gap in mental health care. Bull World Health Organ 2004; 82(11): 858-66.
[PMID: 15640922]
[78]
Dubey NK, Kumar R, Tripathi P. Global promotion of herbal medicine: India’s opportunity. Curr Sci 2004; 86(1): 37-41.
[79]
Scott J. Using Health Belief Models to understand the efficacy-effectiveness gap for mood stabilizer treatments. Neuropsychobiology 2002; 46(Suppl. 1): 13-5.
[http://dx.doi.org/10.1159/000068022] [PMID: 12571427]
[80]
Bickers D, Calow P, Greim H, et al. A toxicologic and dermatologic assessment of linalool and related esters when used as fragrance ingredients. Food Chem Toxicol 2003; 41(7): 919-42.
[http://dx.doi.org/10.1016/S0278-6915(03)00016-4] [PMID: 12804649]
[81]
Di Sotto A, Mazzanti G, Carbone F, Hrelia P, Maffei F. Genotoxicity of lavender oil, linalyl acetate, and linalool on human lymphocytes in vitro. Environ Mol Mutagen 2011; 52(1): 69-71.
[http://dx.doi.org/10.1002/em.20587] [PMID: 20839219]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy