(+)-Cedrol

222.37

222.37

201-035-6

DTXSID1041269

Needles from dilute methanol|Colorless crystals

29062990

20.23000

4.77

Pale yellow to yellow green solid; Sweet fruity cedar-like aroma

1.0±0.1 g/cm3

86 °C

273 °C(lit.)

200 °F

1.519

In water, 11.3 mg/L at 25 °C (est)

2-8°C

8.6X10-5 mm Hg at 25 °C (est)

LD50 skin in rabbit: > 5gm/kg

D28 +9.9° (c = 5 in chloroform)

Woody-earthy

Henry's Law constant = 1.8X10-6 atm-cu m/mole at 25 °C (est)

Hydroxyl radical reaction rate constant = 2.0X10-11 cu cm/molec-sec at 25 °C (est)

NONH for all modes of transport

2

22-24/25

PB7728666

Stable under recommended storage conditions.

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging: Dispose of as unused product.

Incompatible materials: Strong oxidizing agents

|H411 (99.94%): Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]|P273, P391, and P501|Aggregated GHS information provided by 1815 companies from 5 notifications to the ECHA C&L Inventory.

Respiratory protection: Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).|Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific workplace. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.|Skin protection: Handle with gloves.|Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166 (EU).

Advice for firefighters: wear self contained breathing apparatus for firefighting if necessary.|Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Sweep up and shovel into closed containers.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.|Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas.

...produced slight /skin/ irritation.

Cedrol was detected in the emissions from the burning of incense(1); concentration in the emissions and backround air ranged from 299-1080 pg/cu m(1). Cedrol was identified in the volatile biogenic emissions from pine trees(2). Cedrol was identified as a volatile emission compound emitted by microbial activity of Penicillium italicum, a fungi commonly found in indoor environments(3). Cedrol was identified in the volatile emissions of leaves from Juniperus excelsa plant(4). The compound is found in Texas and Virginia cedarwood oil, present at 19.0 and 15.8%, respectively(5).

IDENTIFICATION AND USE: Cedrol forms colorless crystals. It is found in the wood of cypresses and cedars such as Cedrus atlantica, Cupressus sempervirens, and Juniperus virginiana. It is used in fragnances and as a flavor ingredient in foods and traditional medicine. HUMAN EXPOSURE AND TOXICITY: In an exposure study, odorized and blank air was presented to 26 healthy adult volunteers. A constant concentration of cedrol was presented for 10 minutes with 8 minute blank air intervals. Cedrol caused a relaxant effect with decreased heart rate, respiratory rate, systolic and diastolic blood pressure and increased baroreflex activity. Parasympathetic activity was increased and sympathetic activity was decreased. In another exposure study, a maximization test was carried out with 8% cedrol in petrolatum on 25 male volunteers. Sensitization reactions were observed in 2/25 volunteers. In a pre-test for a human maximization study, no irritation was observed to 8% cedrol, when applied for 48 hr under occlusion on five volunteers. In another study, Pyrolae herba (PHVO) was evaluated for antiproliferative activity against human chondrosarcoma cells. A total of 12 components in PHVO were identified. The major compounds included cedrol (17.08%). PHVO demonstrated potent antitumor activity against SW1353 cells, suggesting its potential use as a therapeutic agent in the treatment of chondrosarcoma. In another study, the aim was to investigate the inhibitory effects of cedrol on the activities of eight major human cytochrome P-450 (CYP) enzymes to assess potential cedrol drug interactions. Cedrol, was found to be a potent competitive inhibitor of CYP2B6-mediated bupropion hydroxylase with inhibition constant (Ki) values of 0.9 uM, comparable with that of a selective CYP2B6 inhibitor, thioTEPA (Ki, 2.9 uM). Cedrol also markedly inhibited CYP3A4-mediated midazolam hydroxylation with a Ki value of 3.4 uM, whereas beta-cedrene moderately blocked CYP3A4. Cedrol at 100 microM negligibly inhibited CYP1A2, CYP2A6, and CYP2D6 activities. Cedrol weakly inhibited CYP2C8, CYP2C9, and CYP2C19 activities, but beta-cedrene did not. These in vitro results indicate that cedrol should be examined for potential pharmacokinetic drug interactions in vivo due to their potent inhibition of CYP2B6 and CYP3A4. ANIMAL STUDIES: A 28-day oral toxicity study was conducted to evaluate toxicity of cedrol in rats. Sixty rats were randomly divided into five groups (10 males or 10 females per group) and a control group of 10 animals. Approximately 0.169% w/v of cedrol was administered at dose of 8.4 mg/kg/day in 20 rats (10/sex) seven days per week via gavage to all the animals for 30 days. Crooked incisors and a swollen mouth were observed in one male rat on day 28. Decrease in absolute brain weight and brain-and ovary-to body weight was observed in female rats. However, these findings were not consistent between the sexes and absence of correlative clinical changes made the consideration of these non-adverse findings of limited toxicological significance. Open epicutaneous tests were carried out in outbred male and female guinea pigs with 8% cedrol, no sensitization reactions were observed. In another study on the sedative effects of cedrol, rats and mice were exposed at 1.0 liter/ minute for 30 minutes. Cumulative spontaneous motor activity was found to be significantly decreased in the cedrol exposed group.

LD50 Rabbit Dermal > 5g/kg

Cedrol occurs naturally in the wood of several conifers, particularly cypress and cedar (Cedrus atlantica, Cupressus sempervirens, Juniperus virginiana and others)(1). Cedrol occurs naturally in cedar wood oil from Texas (Juniperus mexicana) and China (Cupressus funebris)(2).

Cedrol's production and use as a feedstock for the manufacture of perfumery compounds(1) and use as a flavoring compound in foods(2) may result in its release to the environment through various waste streams(SRC). Its use as a perfumery compound and odorant for disinfectants(3) will result in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1230(SRC), determined from a structure estimation method(2), indicates that cedrol is expected to have low mobility in soil(SRC). Volatilization of cedrol from moist soil surfaces may occur(SRC) given an estimated Henry's Law constant of 1.8X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(2). Cedrol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.6X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Utilizing the OECD 301F test (manometric respirometry), 88% of the Theoretical BOD was reached in 4 weeks(3) indicating that biodegradation is an important environmental fate process(SRC); results of the test classified cedrol as readily biodegradable(3).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1230(SRC), determined from a structure estimation method(2), indicates that cedrol is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 1.8X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 31 and 230 days, respectively(SRC). According to a classification scheme(4), an estimated BCF of 330(SRC), from an estimated log Kow of 4.33(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is high, provided the compound is not metabolized by the organism(SRC). Utilizing the OECD 301F test (manometric respirometry), 88% of the Theoretical BOD was reached in 4 weeks(5) indicating that biodegradation is an important environmental fate process(SRC); results of the test classified cedrol as readily biodegradable(5). Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions(3).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), cedrol, which has an estimated vapor pressure of 8.6X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase cedrol is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 19 hours(SRC), calculated from its rate constant of 2.0X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Particulate-phase cedrol may be removed from the air by wet and dry deposition(SRC). Cedrol does not contain chromophores that absorb at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of cedrol with photochemically-produced hydroxyl radicals has been estimated as 2.0X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 19 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Cedrol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Cedrol does not contain chromophores that absorb at wavelengths >290 nm(2) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 330 was calculated in fish for cedrol(SRC), using an estimated log Kow of 4.33(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is high, provided the compound is not metabolized by the organism(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of cedrol can be estimated to be 1230(SRC). According to a classification scheme(2), this estimated Koc value suggests that cedrol is expected to have low mobility in soil.

The Henry's Law constant for cedrol is estimated as 1.8X10-6 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that cedrol is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 31 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 230 days(SRC). Cedrol's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). Cedrol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.6X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(1).

According to the 2012 TSCA Inventory Update Reporting data, 2 reporting facilities estimate the number of persons reasonably likely to be exposed during the manufacturing, processing, or use of cedrol in the United States may be <50-99 workers per plant; the data may be greatly underestimated due to confidential business information (CBI) or unknown values(1).|NIOSH (NOES Survey 1981-1983) has statistically estimated that 6,301 workers (4,257 of these were female) were potentially exposed to cedrol in the US(1). Occupational exposure to cedrol may occur through inhalation and dermal contact with this compound at workplaces where cedrol is produced or used. Monitoring and use data indicate that the general population may be exposed to cedrol via inhalation of ambient air, ingestion of food, and dermal contact with consumer products containing cedrol(SRC).

Cedrol, beta-cedrene, and thujopsene are bioactive sesquiterpenes found in cedar essential oil and exert antiseptic, anti-inflammatory, antispasmodic, tonic, astringent, diuretic, sedative, insecticidal, and antifungal activities. These compounds are used globally in traditional medicine and cosmetics. /Traditional use/

Incubation of alpha-cedrol and caryophyllene oxide with Neurospora crassa /identified/ 12beta-hydroxy cedrol, 10alpha-hydroxycedrol, and 3beta-hydroxy cedrol, and 12beta-hydroxy caryophyllene oxide as major metabolites, respectively. The antibacterial and radical scavenging activities of the metabolites were evaluated in vitro using broth microdilution and bioauthographic techniques. However, no significant antibacterial and antioxidant activities were observed ...|Microbial transformation of (+)-cedrol was investigated by using Staphylococcus epidermidis and found that stereospecific hydroxylation of (+)-cedrol occurred at the C-3 position to form (+)-(3S)-3-hydroxycedrol.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Higher alcohols (>3 carbons) and related compounds/|/SRP:/ Basic Treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for shock and treat if necessary ... . Monitor for pulmonary edema and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Higher alcohols (>3 carbons) and related compounds/|/SRP:/ Advanced Treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques, with a bag-valve-mask device, may be beneficial. Consider drug therapy for pulmonary edema ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Monitor for signs of hypoglycemia (decreased LOC, tachycardia, pallor, dilated pupils, diaphoresis, and/or dextrose strip or glucometer readings below 50 mg) and administer 50% dextrose if necessary ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Higher alcohols (>3 carbons) and related compounds/

/HUMAN EXPOSURE STUDIES/ Odorized and blank air was presented to 26 healthy adult volunteers using an olfactometer with separate teflon-coated tubing and face mask systems to prevent deposition of cedrol particles. A constant concentration of 14.20 +/- 1.7 ug/L; 64 +/- 7.7x10-9 cedrol was presented for 10 minutes with 8 minute blank air intervals. Measurements of the subjects' ECGs, heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure and respiratory rate (RR) were recorded. Statistical differences between control air and odorized air were based on the paired t-test. Cedrol caused a relaxant effect with decreased heart rate, respiratory rate, systolic and diastolic blood pressure and increased baroreflex activity. Parasympathetic activity was increased and sympathetic activity was decreased.|/HUMAN EXPOSURE STUDIES/ A maximization test was carried out with 8% (5520 ug/sq cm) cedrol in petrolatum on 25 male volunteers. Cedrol was applied under occlusion to the same site on the forearms of all subjects for five alternate-day 48-hour periods. Patch sites were pretreated for 24 hr with 5% aqueous sodium lauryl solution (SLS) under occlusion. Following a 10-day rest period, a challenge patch was applied to a fresh site for 48 hr under occlusion. Challenge test sites were pre-tested with 10% aqueous SLS for one hour under occlusion. The challenge sites were read at patch removal and 24 hr after patch removal. Sensitization reactions were observed in 2/25 volunteers. However, when this same test was repeated, using the same method and cedrol concentration, no sensitization reactions were observed.|/HUMAN EXPOSURE STUDIES/ In a pre-test for a human maximization study, no irritation was observed to 8% cedrol, when applied for 48-hr under occlusion on five male volunteers.|/ALTERNATIVE and IN VITRO TESTS/ The objective of the present study was to identify chemical constituents of volatile oil from Pyrolae herba (PHVO) and evaluate the antiproliferative activity of PHVO against SW1353 human chondrosarcoma cells. The volatile oil from Pyrolae herba was prepared by hydrodistillation and characterized by gas chromatography-mass spectroscopy (GC-MS). A total of 12 components in PHVO were identified representing 81.62% of the total integrated chromatographic peaks. The major compounds were found to be n-hexadecanoic acid (29.29%), cedrol (17.08%), 6,10,14-trimethyl-2-pentadecanone (9.59%) and cis-9-octadecadienoic acid (8.23%). The antiproliferative activity of PHVO against SW1353 cells was investigated using MTT assay, flow cytometry and western blot analysis. Our results demonstrated that PHVO inhibited SW1353 cell viability in a dose- and time-dependent manner. Furthermore, PHVO treatment decreased the number of cells entering the S phase and caused a reduction in the expression of cyclin D1, cyclin-dependent kinase (CDK)4 and CDK6, whereas it caused an increase in the expression of p21. PHVO demonstrated potent antitumor activity against SW1353 cells, suggesting its potential use as a therapeutic agent in the treatment of chondrosarcoma. /PHVO/|/ALTERNATIVE and IN VITRO TESTS/ Cedrol, beta-cedrene, and thujopsene are bioactive sesquiterpenes found in cedar essential oil and exert antiseptic, anti-inflammatory, antispasmodic, tonic, astringent, diuretic, sedative, insecticidal, and antifungal activities. These compounds are used globally in traditional medicine and cosmetics. The aim of this study was to investigate the inhibitory effects of cedrol, beta-cedrene, and thujopsene on the activities of eight major human cytochrome P-450 (CYP) enzymes using human liver microsomes to assess potential beta-cedrene-, cedrol-, and thujopsene-drug interactions. Cedrol, beta-cedrene, and thujopsene were found to be potent competitive inhibitors of CYP2B6-mediated bupropion hydroxylase with inhibition constant (Ki) values of 0.9, 1.6, and 0.8 uM, respectively, comparable with that of a selective CYP2B6 inhibitor, thioTEPA (Ki, 2.9 uM). Cedrol also markedly inhibited CYP3A4-mediated midazolam hydroxylation with a Ki value of 3.4 microM, whereas beta-cedrene and thujopsene moderately blocked CYP3A4. Cedrol, beta-cedrene, and thujopsene at 100 uM negligibly inhibited CYP1A2, CYP2A6, and CYP2D6 activities. Only thujopsene was found to be a mechanism-based inhibitor of CYP2C8, CYP2C9, and CYP2C19. Cedroland thujopsene weakly inhibited CYP2C8, CYP2C9, and CYP2C19 activities, but beta-cedrene did not. These in vitro results indicate that cedrol, beta-cedrene, and thujopsene need to be examined for potential pharmacokinetic drug interactions in vivo due to their potent inhibition of CYP2B6 and CYP3A4.

1H-3a,7-Methanoazulen-6-ol, octahydro-3,6,8,8-tetramethyl-, (3R,3aS,6R,7R,8aS)-: ACTIVE|Found in the wood of several conifers, particularly cypresses and cedars such as Cedrus atlantica, Cupressus sempervirens, and Juniperus virginiana.

Food additives -> Flavoring Agents|Flavouring Agent -> FLAVOURING_AGENT; -> JECFA Functional Classes|Flavoring Agents -> JECFA Flavorings Index

Flavoring Agents|Flavouring Agent -> FLAVOURING_AGENT;