Absorption, Distribution and Excretion
Linalool may permeate porcine (and by extension also human) buccal mucosa in function of its concentration (14.46% w/w) and of formulation /as in the essential oil of Salvia desoleana Atzei & Picci/
Based on experiments with rats using (14)C-labelled substance, linalool is rapidly absorbed from the intestinal tract following oral uptake ... judging from the delay in fecal excretion, intestinal absorption is complete. Subsequent to absorption, linalool is metabolized rapidly, with urinary excretion of (14)C activity starting without delay. Several hours after gavage, substantial amounts of radioactivity were detected in the expired air as (14)CO2, evidencing complete intermediary metabolism. Fecal excretion of radioactivity was delayed and found mostly between 36 and 48 hours after dosing, suggesting entero-hepato-biliary re-circulation; this re-circulation was confirmed in a second experiment involving cross-linking a treated and an untreated rat with a biliary-to-intestinal cannula and subsequent radio-analysis. Overall, approximately 60% of the total excreted dose was found in urine over 72 hours after administration; approximately 23% of activity was detected in exhaled air and approximately 15% was found in the feces; there is no indication of tissue accumulation of linalool whatsoever. The study suggests that large doses of oral linalool will be metabolized in the rat by conjugation and excretion in urine and bile, while a substantial proportion will enter intermediary metabolisms up to the formation of carbon dioxide and pulmonary excretion. Entero-hepato-biliary re-circulation may have the effect of enhancing the metabolic load on the liver over a certain period.
After a 1 hour inhalation of 27 mg linalool ... /mouse/ plasma levels of linalool 30, 60 and 90 min after exposure: about 1, 2.7 and 2.9 ng/mL.
Linalool applied to mouse skin was not absorbed within two hours.

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Metabolism / Metabolites
... Metabolites isolated from urine of rats after oral administration of linalool (VII) were 8-hydroxy-linalool (VIII) and 8-carboxy-linalool (IX). After three days of feeding rats with either geraniol or linalool, liver-microsomal cytochrome P-450 was increased. Both NADH- and NADPH-cytochrome c reductase activities were not significantly changed during the six days of treatment. Oral administration of these two terpenoids did not affect any of the lung-microsomal parameters measured.
Based on experiments with rats using (14)C-labelled substance ... subsequent to absorption, linalool is metabolized rapidly, with urinary excretion of (14)C activity starting without delay. Several hours after gavage, substantial amounts of radioactivity were detected in the expired air as (14)CO2, evidencing complete intermediary metabolism. Fecal excretion of radioactivity was delayed and found mostly between 36 and 48 hours after dosing, suggesting entero-hepato-biliary re-circulation ... Entero-hepato-biliary re-circulation may have the effect of enhancing the metabolic load on the liver over a certain period.
For the induction study 600 mg linalool/kg bw was administered /to male IISc strain rats/ once daily for 6 days by gastric tube as a suspension in 1% methyl cellulose solution. Control rats were only given the vehicle. For the identification of metabolites, 800 mg linalool/kg bw was administered once daily for 20 days ... . 8-Hydroxy-linalool and 8-carboxy-linalool were identified in the urine, showing selective oxidation of the C8-methyl in linalool. The 8-hydroxylase present in both lung and liver microsomes was shown to be mediated by a cytochrome P-450 (CYP450) system. After 3 days of dosing, liver and lung microsomal CYP450 was increased; on the other hand, both NADH- and NADPH-cytochrome c reductase activities were not significantly changed during the 6 days of treatment. /Purity > 99.5%/
... Hydrolysis occurs more rapidly at the low pH of gastric fluids. The reaction products are linalool and acetic acid (ester hydrolysis). This is supported by the findings of the hydrolysis study ... at pH 4, 7 and 9. Therefore it is expected that linalool is the substance that will enter the systemic circulation after oral uptake of linalyl acetate. Linalool is probably converted to geraniol and its metabolites, 1,5-dimethyl-hexadiene-1,6-dicarboxylic acid and 7-carboxy-5-methylocto-6-enoic acid ... /linalool acetate/
For more Metabolism/Metabolites (Complete) data for LINALOOL (7 total), please visit the HSDB record page.

Toxicity Summary
IDENTIFICATION AND USE: Linalool is a colorless liquid with a spicy herbal odor. It is used as fragrance component in perfumes, cosmetics, soaps, and detergents; flavoring agent in foods. It is also used as a synthetic intermediate. It is registered for pesticide use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. HUMAN EXPOSURE AND TOXICITY: Linalool at concentrations up to 20% was consistently found not to be a sensitizer in human maximization tests. It was not phototoxic or photoallergenic in human tests. Linalool can cause allergic contact dermatitis. Linalool was not genotoxic when tested in vitro by the micronucleus test on peripheral human lymphocytes. ANIMAL STUDIES: Linalool was irritating to rabbit skin. Series of Draize tests with fragrance materials indicated that linalool was not a sensitizer in guinea pigs. Repeated application on sheep skin caused signs comparable to acanthosis. Rats were admin linalool 1500 mg/kg/day by gavage for 5 days. Absolute and relative liver weights were increased in treated animals; microsomal protein content was decreased. Psychopharmacological evaluation of linalool in vivo in rats showed that it has marked dose-dependent sedative effects on the central nervous system, including hypnotic, anticonvulsant and hypothermic properties. The study reports an inhibitory effect of linalool on glutamate binding in the rat cortex. In cats signs of toxicosis include hypersalivation, muscle tremors, ataxia, depression, and hypothermia. The sedative properties of linalool were investigated in mice. The significant decrease in the motility of female and male laboratory animals under standardized experimental conditions is found to be closely dependent on the exposure time. 10/sex/treatment rats received daily oral doses of 160, 400 or 1000 mg/kg bw linalool during 28 days. One male and one female of the high dose group were found dead. From a 28-day subchronic toxicity study with the essential oil of coriander with 72.9% linalool and 22.3% other identified terpenoids no remarkable effects on the primary reproductive organs in both females (ovaries and uteri) and males (testes and epididymides) was noted in any animal from any dosage group up to 1000 mg/kg bw/day, both macroscopically at dissection and also microscopically during histopathology of every (10 male, 10 female) high-dose animal. The genotoxic potential of linalool has been evaluated for mutagenicity in bacteria and in cultured mouse L5718Y tk+/. cells, and by cytogenicity in Chinese hamster ovary (CHO) cells via SCE, a chromosome aberration study, and an in vivo micronucleus test. The mutagenicity and clastogenicity data are sufficient to indicate that linalool is not genotoxic. ECOTOXICITY STUDIES: For linalool, LC50 > 28.8 ppm for Rainbow Trout, a LC50 of 36.8 ppm for Bluegill, and a LC50 of 36.7ppm for aquatic invertebrates.

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Interactions
Acrylamide (ACR) is a water-soluble monomer which has broad application in different industries and also can form in food during heating process. This monomer is a potent neurotoxicant and damages the central and the peripheral nervous system in human and animals. Oxidative stress has been mentioned as an important pathway in ACR neurotoxicity, therefore the purpose of the current study was evaluation of possible effects of linalool which is a natural enantiomer monoterpene compound. Linalool has shown antioxidant properties in several studies. Male Wistar rats were treated with ACR (50 mg/kg ip) alone or with linalool (12.5, 25, 50 and 100 mg/kg ip) for 11 days. In another 2 groups rats were treated with linalool (12.5 mg/kg ip) 3 days after and before ACR administration. Then behavior index (gait score) was examined for rats. After that, rats were sacrified and malondialdehyde (MDA) as a marker of lipid peroxidation and glutathione (GSH) content were determined in brain tissue. Exposure to ACR led to severe gait abnormalities and treatment with linalool significantly reduced abnormalities. ACR reduced GSH content and increased level of MDA in cerebral cortex. Linalool increased GSH content while decreased ACR-induced lipid peroxidation in rat brain tissue and the best protocols were initiation of supplementation before or simultaneous with ACR administration.
We studied the protective effect of monoterpenes myrcene, eucalyptol and linalool against t-butyl hydroperoxide (t-BOOH) induced genotoxicity in reverse mutation assay with Escherichia coli WP2 IC185 strain and its oxyR mutant IC202, and with the comet assay in human hepatoma HepG2 and human B lymphoid NC-NC cells. The monoterpenes were tested in concentration ranges 0.05-1.5 mg/plate and 0.01-1.0 ug/mL in bacteria and mammalian cells, respectively. Suppression of t-BOOH induced mutagenesis was detected only in IC202 strain, and correlated with the observed inhibition of lipid peroxidation by the three monoterpenes. Linalool and myrcene strongly suppressed t-BOOH induced mutagenesis. Eucalyptol, in addition to moderate suppression of t-BOOH induced mutagenesis, suppressed also spontaneous mutagenesis. In NC-NC cells linalool and myrcene reduced t-BOOH induced DNA damage by about 50% at 0.01 ug/mL, while eucalyptol was less efficient (about 50% reduction at 1.0 ug/mL). In HepG2 cells linalool and eucalyptol reduced DNA damage by 30% and 40%, respectively, while myrcene was ineffective. The repair of t-BOOH induced DNA damage, studied in HepG2 cells, was not affected by monoterpenes. The results indicate that linalool, eucalyptol and myrcene have substantial protective effect against oxidant induced genotoxicity, which is predominately mediated by their radical scavenging activity.
... The present work ... reports data evaluating the chemopreventive effects of limonene and five other monoterpenes with various chemical structures using a 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary carcinogenesis model. The terpenes tested include: oxygenated ((-)-menthol) and non-oxygenated (d-limonene) monocyclic forms, oxygenated (1,8-cineole) and non-oxygenated ((+/-)-alpha-pinene) bicyclic forms and oxygenated ((+/-)-linalool) and non-oxygenated (beta-myrcene) acyclic forms. Dietary additions of each of the monocyclic terpenes, d-limonene or (-)-menthol resulted in a significant inhibition of mammary carcinogenesis. Furthermore, menthol was found to be a more potent chemopreventive agent than limonene during the DMBA initiation of rat mammary tumors. The acyclic and bicyclic terpenes had no significant chemopreventive activities at the dose levels used in these studies.
The sedative properties of the essential oil of Lavender (Lavandula angustifolia Miller) and of its main constituents--linalool and linalyl acetate--were investigated in mice followed up in a series of experimental procedures. The significant decrease in the mobility of female and male laboratory animals under standardized experimental conditions is found to be closely dependent on the exposure time to the drugs. Nevertheless after an injection of caffeine into mice a hyperactivity was observed which was reduced to nearly a normal motility only by inhalation of these fragrance drugs. ...
... The present work ... reports data evaluating the chemopreventive effects of limonene and five other monoterpenes with various chemical structures using a 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary carcinogenesis model. The terpenes tested include: oxygenated ((-)-menthol) and non-oxygenated (d-limonene) monocyclic forms, oxygenated (1,8-cineole) and non-oxygenated ((+/-)-alpha-pinene) bicyclic forms and oxygenated ((+/-)-linalool) and non-oxygenated (beta-myrcene) acyclic forms. Dietary additions of each of the monocyclic terpenes, d-limonene or (-)-menthol resulted in a significant inhibition of mammary carcinogenesis. Furthermore, menthol was found to be a more potent chemopreventive agent than limonene during the DMBA initiation of rat mammary tumors. The acyclic and bicyclic terpenes had no significant chemopreventive activities at the dose levels used in these studies.

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Non-Human Toxicity Values
LD50 Rat oral 2790 mg/kg (2440-3180, 95% CL) /From table/
LD50 Rat dermal 5610 mg/kg
LD50 Rat ip 307 mg/kg /From table/
LD50 Mouse oral 3000 mg/kg /From table/
For more Non-Human Toxicity Values (Complete) data for LINALOOL (9 total), please visit the HSDB record page.

[1]. The protective and therapeutic effects of linalool against doxorubicin-induced cardiotoxicity in Wistar albino rats. Hum Exp Toxicol. 2019 Apr 12:960327119842634.

[2]. Linalool is a PPARα ligand that reduces plasma TG levels and rewires the hepatic transcriptome and plasma metabolome. J Lipid Res. 2014 Jun;55(6):1098-110.

[3]. Antitumorigenic potential of linalool is accompanied by modulation of oxidative stress: an in vivo study in sarcoma-180 solid tumor model. Nutr Cancer. 2014;66(5):835-48.

[4]. Anti-cancer mechanisms of linalool and 1,8-cineole in non-small cell lung cancer A549 cells. Heliyon. 2020 Dec 15;6(12):e05639.

[5]. Recent updates on bioactive properties of linalool. Food Funct. 2021 Nov 1;12(21):10370-10389.

Linalool is a monoterpenoid that is octa-1,6-diene substituted by methyl groups at positions 3 and 7 and a hydroxy group at position 3. It has been isolated from plants like Ocimum canum. It has a role as a plant metabolite, a volatile oil component, an antimicrobial agent and a fragrance. It is a tertiary alcohol and a monoterpenoid.
Linalool has been reported in Camellia sinensis, Aristolochia triangularis, and other organisms with data available.
3,7-Dimethyl-1,6-octadien-3-ol is a metabolite found in or produced by Saccharomyces cerevisiae.
See also: Clary Sage Oil (part of); Cinnamon Leaf Oil (part of); Cinnamon Bark Oil (part of) ... View More ...

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Mechanism of Action
... The specific toxic effect of linalool on animals is therefore likely to be caused by its neurotoxic respectively neuropharmacological mode of action. In turn, this may explain the use of linalool-containing natural products (aromatic herbs and spices or their essential oils respectively extracts) in traditional medicinal systems, specifically for their sleep-inducing and anticonvulsant purposes. Moreover, it also accounts for the widespread traditional use of herbs containing linalool for stored-food pest control for the use of linalool-containing extracts as a pet flea insecticide.

C10H18O

154.25

154.135

78-70-6

Linalool-d3;1216673-02-7

6549

Colorless to light yellow liquid

0.9±0.1 g/cm3

198.5±0.0 °C at 760 mmHg

Freezing point: below -74 °C /OECD Guideline 102 (Melting point / Melting Range)/
< 25 °C

76.1±0.0 °C

0.1±0.8 mmHg at 25°C

1.463

3.28

1

1

4

11

154

0

O([H])C(C([H])=C([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])/C(/[H])=C(\C([H])([H])[H])/C([H])([H])[H]

CDOSHBSSFJOMGT-UHFFFAOYSA-N

InChI=1S/C10H18O/c1-5-10(4,11)8-6-7-9(2)3/h5,7,11H,1,6,8H2,2-4H3

3,7-dimethylocta-1,6-dien-3-ol

AI3 00942 AI3-00942 Linalool

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~648.30 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (16.21 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (16.21 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (16.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)