Absorption, Distribution and Excretion
The profile of the geraniol concentrations in rat blood following oral administration of the emulsified formulation was characterized by a peak concentration at 30 min of about 270 μg/mL and an area under concentration (AUC) similar to that obtained by the intravenous administration of the same geraniol dose, indicating an absolute bioavailability of 92%. Geraniol appears able to permeate directly from the bloodstream to the central nervous system following its oral administration to rats, reaching detectable amounts in the CSF; peak concentration in the CSF was found to be about 2.5 μg/mL and was observed 30 min after oral administration.

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Metabolism / Metabolites
Metabolites isolated from the urine of rats after oral administration of geraniol (I) were: geranic acid (II), 3-hydroxy-citronellic acid (III), 8-hydroxy-geraniol (IV), 8-carboxy-geraniol (V) and Hildebrandt acid (VI). 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.
The fragrance compound geraniol is susceptible to autoxidation when in contact with air, and to cutaneous metabolism. In both processes, the isomeric aldehydes geranial and neral are formed. ...
Male IISc rats were given (1-(3)H)geraniol in daily doses of 800 mg/kg bw by gavage for 20 consecutive days. Five urinary metabolites were identified via two primary pathways. In one pathway, the alcohol is oxidized to yield geranic acid (3,7-dimethyl-2,6-octadienoic acid) which is subsequently hydrated to yield 3, 7-dimethyl-3-hydroxy-6-octenoic acid (3-hydroxy citronellic acid). In a second pathway, the alcohol undergoes selective omega-oxidation of the C8-methyl to yield 8-hydroxygeraniol and 8-carboxygeraniol, the latter of which undergoes further oxidation to the principal urinary metabolite 2,6-dimethyl-2,6-octadienedioic acid (Hildebrandt acid) ... . It was demonstrated that administration of geraniol at a dose of 600 mg/kg bw by gavage for 1, 3 or 6 days induced expression of rat liver microsomal cytochrome P450 and geraniol hydroxylation, but not the activities of rat liver microsomal cytochrome b5, NADPH-cytochrome c reductase, and NADH-cytochrome c reductase, nor the activities of these enzymes in rat lung microsomes ... . Rabbits are also capable of omega-oxidation of geraniol, as both the Hildebrandt acid and its dihydro form (2,6-dimethyl-2-octendioic acid; reduced or dihydro-Hildebrandt acid) were isolated from the urine of treated animals... . In both rabbits and rats, the omega-hydroxylation is mediated by the cytochrome P450 system and requires NADPH and oxygen ... . It has been demonstrated that not only rat liver microsomes are capable of omega-hydroxylating geraniol, but also rat lung and kidney microsomes
Geraniol has known human metabolites that include [(2E)-3,7-Dimethylocta-2,6-dienyl] hydrogen sulfate.

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Biological Half-Life
In vitro measurements indicated that geraniol is highly stable in human and rat whole blood, whereas following intravenous administration geraniol is eliminated from the bloodstream with a relatively short half-life (about 12 min), starting from a concentration of about 300 μg/mL.

Toxicity Summary
IDENTIFICATION AND USE: Geraniol is colorless to pale-yellow, liquid oil. It has a sweet rose like odor. Geraniol is one of the most frequently used terpenoid fragrance materials. It can be used in all flowery-rose like compositions and does not discolor soaps. In flavor compositions, geraniol is used in small quantities to accentuate citrus notes. It is also used in alcoholic and nonalcoholic beverages, baked goods, chewing gum, frozen dairy, gelatin (pudding), gravies, hard candy, meat products, soft candy. It is an important intermediate in the manufacture of geranyl esters, citronellol, and citral. HUMAN EXPOSURE AND TOXICITY: A report of a 32 year old female patient working in a company for baking ingredients, who had been handling grated lemon peel and lemon oil for several years, developed allergic contact dermatitis of the fingers of both her hands. The material responsible for the dermatitis was identified as geraniol in both lemon peel and lemon oil and it proved to be the only source of the allergic reaction. In a human patch test, geraniol at a 32% concentration was severely irritating and geranyl acetate mildly irritating. Occupational exposure to geraniol may occur through inhalation and dermal contact with this compound at workplaces where geraniol is produced or used. Monitoring data indicate that the general population may be exposed to geraniol by inhalation through use of consumer products, ingestion of food, and dermal contact with this compound and other consumer products containing geraniol. Single compounds (SC) of fragrance mix (FM) contribute differently to FM patch test reactions. The data collected by the Information Networks of the Departments of Dermatology multicenter project from 1996-2002 were analyzed. SCs were tested in a selected group of patients, ranging from n=1083 to n=1924 per year. Reactions to SCs in FM positive patients were observed in 29% (oak moss absolute) to 5.9% geraniol. There was no time trend in reactions to SC's, although the relative share was increased for isoeugenol, cinnamic aldehyde and geraniol in 1999. ANIMAL STUDIES: Geraniol is described as not irritating in the rabbit acute dermal irritation corrosion test. It was not sensitizing in the guinea pig maximization test. Groups of five male and five female weanling rats were given diets containing geraniol for 16 weeks. No treatment related effects on growth, hematological parameters or organ weights, or on macroscopic or microscopic changes in the tissues were observed. An in vitro chromosomal aberration test was conducted in Chinese hamster fibroblast without metabolic activation. Three doses of geraniol were examined and the results were equivocal. Polyploidization effects were observed. The incidence of chromosomal aberrations at 48 hours was in the range considered negative. ECOTOXICITY STUDIES: Essential oil constituents were tested for their neurophysiological effects in Periplaneta americana cockroach and Blaberus discoidalis cockroach. Geraniol had similar depressive effects but increased spontaneous firing at lower doses. Similar effects occurred in dorsal unpaired median (DUM) neurons, recorded intracellularly in the isolated terminal abdominal ganglion of P. americana.

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Interactions
The fragrance terpene geraniol forms sensitizing compounds via autoxidation and skin metabolism. Geranial and neral, the two isomers of citral, are the major haptens formed in both of these activation pathways. /The objective of the study was/ to investigate whether testing with oxidized geraniol detects more cases of contact allergy than testing with pure geraniol. The pattern of reactions to pure and oxidized geraniol, and metabolites/autoxidation products, was studied to investigate the importance of autoxidation or cutaneous metabolism in contact allergy to geraniol. Pure and oxidized geraniol were tested at 2.0% petrolatum in 2227 and 2179 consecutive patients, respectively. In parallel, geranial, neral and citral were tested in 2152, 1626 and 1055 consecutive patients, respectively. Pure and oxidized geraniol gave positive patch test reactions in 0.13% and 0.55% of the patients, respectively. Eight of 11 patients with positive patch test reactions to oxidized geraniol also reacted to citral or its components. Relevance for the positive patch test reactions in relation to the patients' dermatitis was found in 11 of 14 cases. Testing with oxidized geraniol could detect more cases of contact allergy to geraniol. The reaction pattern of the 14 cases presented indicates that both autoxidation and metabolism could be important in sensitization to geraniol.
Geraniol (GO) potent antitumor and chemopreventive effects are attributed to its antioxidant and anti-inflammatory properties. In the current study, the potential efficacy of GO (250 mg/kg) in ameliorating metabolic syndrome (MetS) induced by fructose in drinking water /administered to rats/ was elucidated. Moreover, the effect of pioglitazone (5 and 10 mg/kg; PIO) and the possible interaction of the co-treatment of GO with PIO5 were studied in the MetS model. After 4 weeks of treatment, GO and/or PIO reduced the fasting blood glucose and the glycemic excursion in the intraperitoneal glucose tolerance test. GO and PIO5/10 restrained visceral adiposity and partly the body weight gain. The decreased level of peroxisome proliferator activated receptor (PPAR)-gamma transcriptional activity in the visceral adipose tissue of MetS rats was increased by single treatment regimens. Though GO did not affect MetS-induced hyperinsulinemia, PIO5/10 lowered it. Additionally, GO and PIO5/10 suppressed glycated hemoglobin and the receptor for advanced glycated end products (RAGE). These single regimens also ameliorated hyperuricemia, the disrupted lipid profile, and the elevated systolic blood pressure evoked by MetS. The rise in serum transaminases, interleukin-1beta, and tumor necrosis factor-alpha, as well as hepatic lipid peroxides and nitric oxide (NO) was lowered by the single treatments to different extents. Moreover, hepatic non-protein thiols, as well as serum NO and adiponectin were enhanced by single regimens. Similar effects were reached by the combination of GO with PIO5; however, a potentiative interaction was noted on fasting serum insulin level, while synergistic effects were reflected as improved insulin sensitivity, as well as reduced RAGE and triglycerides. Therefore, GO via the transcriptional activation of PPAR-gamma reduces inflammation and free radical injury produced by MetS. Thereby, these effects provide novel mechanistic insights on GO management of MetS associated critical risk factors. Moreover, the co-administration of GO to PIO5 exalted the antidiabetic drug anti-MetS efficacy.
... The aim of this study was to determine whether blocking /human colonic cancer/ Caco-2 cell differentiation could sensitize the cells to 5-fluorouracil (5-FU) treatment. We show that in cells at confluency, geraniol (400 uM) prevented the formation of brush-border membranes and inhibited the expression of intestinal hydrolases (sucrase, lactase, alkaline phosphatase). The antiproliferative effect of geraniol (400 uM) together with 5-FU (5 uM) was twice that of 5-FU alone. The cytotoxicity induced by 5-FU was enhanced in the presence of geraniol, as shown by a 50% increase of lactate dehydrogenase release in the culture medium. These effects are related to enhanced intracellular accumulation of 5-FU in the presence of geraniol as shown by a 2-fold increase in intracellular 5-[6-(3)H]FU (1.5 uCi/mL).
... The anti-tumoral efficacy of geraniol and 5-fluorouracil were also evaluated on TC-118 human tumors transplanted in Swiss nu/nu mice. ... In nude mice, the combined administration of 5-fluorouracil (20 mg/kg /for 5 days) and geraniol (150 mg/kg /for 5 days) caused a 53% reduction of the tumor volume, whereas a 26% reduction was obtained with geraniol alone, 5-fluorouracil alone showed no effect.
For more Interactions (Complete) data for GERANIOL (6 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Mouse im 4000 mg/kg
LD50 Mouse sc 1090 mg/kg
LD50 Rat oral 3600 mg/kg

[1]. Geraniol interferes with membrane functions in strains of Candida and Saccharomyces. Lipids. 1988 Jun;23(6):534-8.

[2]. Geraniol inhibits prostate cancer growth by targeting cell cycle and apoptosis pathways. Biochem Biophys Res Commun. 2011 Apr 1;407(1):129-34.

[3]. Geraniol, a natural monoterpene, ameliorates hyperglycemia by attenuating the key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats. Pharm Biol. 2017 Dec;55(1):1442-1449.

[4]. Geraniol attenuates oxidative stress, bioaccumulation, serological and histopathological changes during aluminum chloride-hepatopancreatic toxicity in male Wistar rats. Environ Sci Pollut Res Int. 2020 Jun;27(16):20076-20089.

[5]. Antifungal activity of geraniol and citronellol, two monoterpenes alcohols, against Trichophyton rubrum involves inhibition of ergosterol biosynthesis. Pharm Biol. 2015 Feb;53(2):228-34.

Therapeutic Uses
/EXPL THER/ Oral carcinogenesis, a multistep process with multifaceted etiology, arises due to accumulation of heterogeneous genetic changes in the genes involved in the basic cellular functions including cell division, differentiation, and cell death. These genetic changes in the affected cell progressively increase the cell proliferation, angiogenesis, and inhibition of apoptosis. The present study investigated the modulating effect of geraniol on the expression pattern of cell proliferative (PCNA, cyclin D1, c-fos), inflammatory (NF-kappaB, COX-2), apoptotic (p53, Bax, Bcl-2, caspase-3 and -9), and angiogenic (VEGF) markers in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Topical application of 0.5% DMBA in liquid paraffin, three times a week, for 14 weeks, developed well-differentiated squamous cell carcinoma (SCC) in the buccal pouch of golden Syrian hamsters. All the hamsters treated with DMBA alone (100%) developed oral tumors in the buccal pouch after 14 weeks. Over-expression of mutant p53, PCNA, Bcl-2, and VEGF accompanied by decreased expression of Bax were noticed in hamsters treated with DMBA alone. Increased expression of c-fos, COX-2, NF-kappaB, and cyclin D1 and decreased activities of caspase-3 and -9 were also noticed in hamsters treated with DMBA alone. Oral administration of geraniol at a dose of 250 mg/kg bw (body weight) not only completely prevented the formation of oral tumors but also prevented the deregulation in the expression of above mentioned molecular markers in hamsters treated with DMBA. The present results thus suggest that geraniol has potent anti-inflammatory, anti-angiogenic, anti-cell proliferative, and apoptosis-inducing properties in DMBA-induced hamster buccal pouch carcinogenesis.
/EXPL THER/ /The objective of the study was/ to investigate the inhibitory effect of geraniol alone, or in combination with gemcitabine, on the proliferation of BXPC-3 pancreatic cancer cells. BXPC-3 cells were treated under different conditions: with geraniol at 10, 20, 40, 80 and 160 umol/L each for 24 hr, 48 hr or 72 hr; with 20 umol/L geraniol for 24 hr or 0 hr before 20 umol/L gemcitabine for 24 hr; with 20 umol/L geraniol for 24 hr, 48 hr and 72 hr following 20 umol/l gemcitabine for 24 hr; or with 20 umol/L gemcitabine alone as a control. Cell proliferation was assessed and changes in cell morphology were assessed by light and fluorescence microscopy. Apoptosis was detected using flow cytometry. Geraniol inhibited BXPC-3 cell proliferation in a time- and dose-dependent manner. Geraniol alone or combined with gemcitabine induced BXPC-3 cell apoptosis. BXPC-3 inhibition rates with combined treatment were 55.24%, 50.69%, 49.83%, 41.85% and 45.27% following treatment with 20 umol/L geraniol for 24 hr or 0 hr before 20 umol/L gemcitabine for 24 hr, or 20 umol/L geraniol for 24 hr, 48 hr and 72 hr, following 20 umol/L gemcitabine for 24 hr, respectively. Geraniol inhibited the proliferation of BXPC-3 cells. Geraniol significantly increased the antiproliferative and apoptosis-inducing effects of gemcitabine on BXPC-3 cells. Maximum inhibition of BXPC-3 cells was achieved with geraniol treatment for 24 hr before gemcitabine treatment.
/EXPL THER/ Geraniol is an acyclic monoterpene alcohol commonly used as a flavoring agent. The present study was undertaken to investigate antiulcerogenic effects of geraniol and to determine the possible mechanisms involved in this action. In the model of the ethanol-induced ulcer, treatment of rats with geraniol by oral route significantly inhibited gastric lesions by 70% (7.50 mg/kg) to 99% (200 mg/kg). Analysis of the gastric tissue of rats treated with geraniol (7.50 mg/kg) revealed that total glutathione content levels (GSH) increased and levels of myeloperoxidase (MPO) decreased in the gastric mucosa. Oral treatment with geraniol significantly decreased the number of ulcerative lesions induced by ischemia/reperfusion injury by 71% and the duodenal ulcers induced by cysteamine by 68%. The action of geraniol was mediated by the activation of defensive mucosa-protective factors such as the nitric oxide (NO) pathway, endogenous prostaglandins, increased mucus production, increased sulfhydryl compounds, antioxidant properties and the stimulation of calcitonin gene-related peptide (CGRP) release through the activation of transient receptor potential vanilloid (TRPV). The multifaceted gastroprotective mechanisms of geraniol represent a promising option for the treatment of gastric and duodenal mucosa injury.
/EXPL THER/ Parkinson's disease (PD) is a common disabling movement disorder owing to progressive depletion of dopamine in nigrostriatal region, and can be experimentally accelerated by the neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). MPTP-treated mice are a representative animal model for searching for the therapeutic agents for PD without adverse effect. In this study we investigated the effect of geraniol (GE) on chronic MPTP/probenecid (MPTP/p) induced apoptotic changes in nigrostriatal region. We observed that chronic exposure to MPTP/p led to increased expression of apoptotic markers, results in neurodegeneration and motor behavioral impairments in mice. Pretreatment with GE to MPTP/p significantly improved motor functions and ameliorated striatal antioxidant balance. In addition, GE attenuated the expression of apoptotic markers evident by the normalized Bcl-2/Bax ratio and decreased expression of cytochrome-C and caspase-9 in the substantia nigra and striatum of MPTP/p induced mice model of PD. The findings of the present study suggested that GE, a new therapeutic potential avenue may have beneficial effects in slowing or preventing the progression of PD and other neurodegenerative disorders.
For more Therapeutic Uses (Complete) data for GERANIOL (12 total), please visit the HSDB record page.

C10H18O

154.25

154.135

106-24-1

637566

Colorless to light yellow liquid

0.9±0.1 g/cm3

229.5±0.0 °C at 760 mmHg

-15 °C

76.7±0.0 °C

0.0±1.0 mmHg at 25°C

1.471

3.28

1

1

4

11

150

0

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

GLZPCOQZEFWAFX-JXMROGBWSA-N

InChI=1S/C10H18O/c1-9(2)5-4-6-10(3)7-8-11/h5,7,11H,4,6,8H2,1-3H3/b10-7+

(2E)-3,7-dimethylocta-2,6-dien-1-ol

NSC-9279; NSC 9279; Geraniol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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)
H2O : ~1 mg/mL (~6.48 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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Solubility in Formulation 4: 100 mg/mL (648.30 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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