Absorption, Distribution and Excretion
... Permeation of Salvia desoleana Atzei & Picci essential oil (linalyl acetate, 26.8%) through the porcine buccal mucosa is possible in vitro. /Salvia desoleana Atzei & Picci essential oil (linalyl acetate, 26.8%)/
The percutaneous absorption of a massage oil containing lavender oil was studied following application to the skin of a male subject (age 34 yr). Within 5 min after application, traces of linalool and linalyl acetate, the main constituents of lavender oil, could be detected in the blood. After 20 min, maximum concentrations of 100 ng/mL linalyl acetate and 121 ng/mL linalool were reached. Within 90 min most of the lavender oil was eliminated. It was concluded that lavender oil is rapidly absorbed through the skin and is excreted within 90 minutes.

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Metabolism / Metabolites
Esters are readily hydrolyzed by carboxylesterases or esterases. Linalyl acetate has been demonstrated to be hydrolyzed in vitro in rat blood and liver preparations. It is expected to be readily hydrolyzed in vivo. Acetate is a normal constituent of the body. The metabolism of linalool is known and is primarily through glucuronic acid conjugation and excretion
In neutral gastric juice, linalyl acetate is slowly (t1/2=121 min) hydrolyzed to a mixture of linalool and the ring closed isomer alpha-terpineol. In acidic artificial gastric juice, linalyl acetate is rapidly hydrolyzed (t1/2<5 min) to yield linalool, which rapidly rearranges into alpha-terpineol. Linalyl acetate was slowly hydrolyzed (t1/2=153-198 min) in intestinal fluid with or without pancreatin. Linalyl acetate also hydrolyzed in homogenates of rat intestinal mucosal, blood, and liver, but at rates much slower than in acidic gastric juice (rate constant for hydrolysis k=0.01-0.0055/min vs. >5/min). Based on these observations it is concluded that linalyl acetate hydrolyzes in gastric juice to yield linalool which, to some extent, is rapidly ring closed to yield alpha-terpineol.
... 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 ...

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Biological Half-Life
Percutaneous absorption ofthe main components of lavender oil were measured in a male human subject. Blood levels of linalool and linalyl acetate were followed for 90 min after the use of a massage oil which contained lavender oil and peanut oil in a 2:98 ratio. The lavender oil contained 24.79% linalool and 29.59% linalyl acetate. A 1500 mg sample of the lavender oil was gently massaged for 10 min into a 376 sq cm area on the abdomen of a 60 kg male volunteer. Blood samples were drawn from the left cubital vein at 0, 5, 10, 15, 20, 30, 45, 60, 75 and 90 min. After adding heparin to the samples, the plasma was centrifuged and the samples were then stored until they were analyzed. Linalyl acetate was absorbed quickly and trace amounts could be detected in the blood 5 min after finishing the massage. The peak plasma concentration was reached at 19 min with a mean plasma concentration of 121 ng/mL. Most of the linalyl acetate disappeared from the blood in 90 min with a biological half-life of 14.3 min.
Linalyl acetate is hydrolysed in gastric and pancreatic fluids with mean half-lives of 5.5 and 52.6 minutes respectively ...

Toxicity Summary
IDENTIFICATION AND USE: Linalyl acetate is a clear, colorless, oily liquid. It is an excellent fragrance material. It can also be employed in soaps and detergents and as a food additive. It is a component of oil paint. It is used in extracts and as a substitute for petitgrain oil. HUMAN EXPOSURE AND TOXICITY: Application of linalyl acetate in acetone (33%) to the back of male volunteers without known allergies during 48 hours under occlusion did not induce signs of irritation up to 120 hours after removal of the patch. Linalyl acetate is identified as one of the constituents of lavender oil that may cause allergic reactions. Oxidized linalyl acetate could be a common fragrance contact allergen. The potential genotoxicity of linalyl acetate, was evaluated in vitro by the micronucleus test on peripheral human lymphocytes. In the range of non-toxic concentrations (0.5-100 ug/mL), linalyl acetate increased the frequency of micronuclei significantly and in concentration-dependent manner. In a chromosome aberration test with human lymphocytes, linalyl acetate did not induce aberrations, both with and without S-9 mix. ANIMAL STUDIES: Inhalation exposure of mice to 2.74 mg linalyl acetate/L air during 90 minutes led to reduced motor activity compared to untreated controls. The effect was more severe in mice aged 6-8 weeks (up to 100% reduction) than in mice of 6 months (up to 81% reduction). In mice dermal coapplication of linalyl acetate (3 mg in 0.1 mL acetone) with benzo(a)pyrene did slightly increase the number of skin papillomas and carcinomas compared to benzo(a)pyrene controls. An Ames test was performed with linalyl acetate in Salmonella typhimurium strains TA97, TA98, TA100, TA1535 and TA102 with and without metabolic activation. Linalyl acetate was found to be not mutagenic in this assay. An in vitro unscheduled DNA synthesis (UDS) assay was negative in primary rat hepatocytes at doses up to 300 nL/mL. ECOTOXICITY STUDIES: In a 96-hour flow-through test with carps (Cyprinus carpio), fish were exposed to 10, 18, 32, 56 and 100 mg/L (nominal concentrations). Mean measured concentrations were 7.9, 12.3, 20.1, 27.3 and 27.2 mg/L. At the highest concentrations (32 mg/L and above) all fish died. At all concentrations hypoactive swimming behavior, loss of equilibrium and/or immobility was observed.

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Toxicity Data
LC50 (mice) > 1,028 mg/m3/4h

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Interactions
In Swiss mice (ICR/Ha) dermal coapplication of linalyl acetate (3 mg in 0.1 mL acetone) with /5 ug/ benzo(a)pyrene /3 times weekly for 67 wk/ did slightly increase the number of skin papillomas and carcinomas compared to benzo(a)pyrene controls ... .
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 mobility only by inhalation of these fragrance drugs. ...

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Non-Human Toxicity Values
LD50 Rat oral 14,550 mg/kg
LD50 Rat ip 2864 mg/kg (95% C.I. 2414- 3399 mg/kg)
LD50 Rat (female) ip 2984 mg/kg (95% C.I. 2293-3884 mg/kg)
LD50 Rat (male) ip 2778 mg/kg (95% C.I. 2246-3435 mg/kg)
For more Non-Human Toxicity Values (Complete) data for LINALYL ACETATE (6 total), please visit the HSDB record page.

[1]. Anti-inflammatory activity of linalool and linalyl acetate constituents of essential oils,Phytomedicine. 2002 Dec;9(8):721-6.

3,7-dimethylocta-1,6-dien-3-yl acetate is a monoterpenoid that is the acetate ester of linalool. It forms a principal component of the essential oils from bergamot and lavender. It is an acetate ester and a monoterpenoid. It is functionally related to a linalool.
Linalyl acetate has been reported in Angelica gigas, Magnolia officinalis, and other organisms with data available.
Linalyl acetate is found in cardamom. Linalyl acetate is isolated from numerous plants and essential oils, e.g. clary sage, lavender, lemon etc. Linalyl acetate is a flavouring ingredient Linalyl acetate is a naturally-occurring phytochemical found in many flowers and spice plants. It is one of the principal components of the essential oils of bergamot and lavender. Chemically, it is the acetate ester of linalool, and the two often occur in conjunction.
Linalool acetate is a metabolite found in or produced by Saccharomyces cerevisiae.
See also: Clary Sage Oil (part of).

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Mechanism of Action
In a preliminary experiment, ... lavender essential oil relaxed vascular smooth muscle. Thus, the/se/ ... experiments were designed to investigate the relaxation mechanism of linalyl acetate as the major ingredient of lavender essential oil in rabbit carotid artery specimens. Linalyl acetate produced sustained and progressive relaxation during the contraction caused by phenylephrine. The relaxation effect of linalyl acetate at a concentration near the EC50 was partially but significantly attenuated by nitroarginine as an inhibitor of nitric oxide synthase, 1H-(1,2,4)oxadiazolo(4,3-a)quinoxaline-1-one as an inhibitor of guanylyl cyclase, or by the denudation of endothelial cells. In specimens without endothelium, the phenylephrine-induced contraction and phosphorylation of myosin light chain (MLC) were significantly attenuated after the pretreatment with linalyl acetate. The relaxation caused by linalyl acetate in the endothelium-denuded specimens was clearly inhibited by calyculin A as an inhibitor of MLC phosphatase, although not by ML-9 as an inhibitor of MLC kinase. Furthermore, suppression of the phenylephrine-induced contraction and MLC phosphorylation with linalyl acetate was canceled by the pretreatment with calyculin A. These results suggest that linalyl acetate relaxes the vascular smooth muscle through partially activation of nitric oxide/cyclic guanosine monophosphate pathway, and partially MLC dephosphorylation via activating MLC phosphatase.

C12H20O2

196.29

196.146

115-95-7

8294

Colorless to light yellow liquid

0.9±0.1 g/cm3

220.0±0.0 °C at 760 mmHg

85°C

90.0±0.0 °C

0.1±0.4 mmHg at 25°C

1.452

3.83

0

2

6

14

237

0

C=CC(C)(CCC=C(C)C)OC(=O)C

UWKAYLJWKGQEPM-UHFFFAOYSA-N

InChI=1S/C12H20O2/c1-6-12(5,14-11(4)13)9-7-8-10(2)3/h6,8H,1,7,9H2,2-5H3

3,7-dimethylocta-1,6-dien-3-yl acetate

AI3-00941; FEMA No. 2636; Linalyl acetate

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 (~509.45 mM)
Ethanol : ~12.5 mg/mL (~63.68 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.74 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 (12.74 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 (12.74 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.)