1,8-Cineole

154.25

154.25

617-029-5

RV6J6604TK

760388|6171

1993

DTXSID4020616

Colorless liquid or oil|Colorless mobile liquid|Colorless essential oil|Colorless liquid

R - Respiratory system

29329900

9.2

2.5

1,8-cineol is a colorless liquid with a camphor-like odor. Spicy cooling taste. (NTP, 1992)

0.9267 g/cm³ @ Temp: 20 °C

1.5 °C

176.4 °C

49 deg C (120 deg F) - closed cup

1.455-1.46

Soluble in water(3500 mg/L (at 21°C). Miscible with ether, alcohol, chloroform, glacial acetic acid, oils. Soluble in ethanol, ethyl ether; slightly soluble in carbon tetrachloride.

Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage. Recommended storage temperature -20 deg C.

1.90 mm Hg at 25 deg C

LD50 orally in Rabbit: 2480 mg/kg

Camphor-like odor

EUCALYPTUS, BITTER-SWEET FLAVOR

1.11e-11 cm3/molecule*sec

Henry's Law constant = 1.10X10-4 atm-cu m/mol at 25 °C

A terpene ether; congealing point not below 0 °C|Hydroxyl radical reaction rate constant = 1.11X10-11 cu cm/mole-sec at 25 °C|Nitrate radical reaction rate constant = 1.75X10-16 cu cm/mole-sec at 25 °C

Highly flammable. Insoluble in water.

Ethers

Highly Flammable

1,8-CINEOL will react with acids and bases. (NTP, 1992)

III

1993

2

R10; R37/38; R41

26-39-16

Xi,F

Stable. Flammable. Incompatible with acids, bases, strong oxidizing agents.

P210, P233, P240, P241, P242, P243, P280, P303+P361+P353, P370+P378, P403+P235, P501

H226

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.

Incompatible materials: Strong oxidizing agents, Strong acids, Acid chlorides, Acid anhydrides

Cineole is a food additive permitted for direct addition to food for human consumption as a synthetic flavoring substance and adjuvant in accordance with the following conditions: a) they are used in the minimum quantity required to produce their intended effect, and otherwise in accordance with all the principles of good manufacturing practice, and b) they consist of one or more of the following, used alone or in combination with flavoring substances and adjuvants generally recognized as safe in food, prior-sanctioned for such use, or regulated by an appropriate section in this part.

Flash point data for this compound are not available but it is probably combustible. (NTP, 1992)

|Danger|H226 (83.55%): Flammable liquid and vapor [Warning Flammable liquids]|P210, P233, P240, P241, P242, P243, P261, P264, P272, P273, P280, P301+P310, P302+P352, P303+P361+P353, P321, P331, P332+P313, P333+P313, P362, P363, P370+P378, P391, P403+P235, P405, and P501|Aggregated GHS information provided by 315 companies from 20 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Warning|H226 (99.01%): Flammable liquid and vapor [Warning Flammable liquids]|P210, P233, P240, P241, P242, P243, P261, P272, P280, P302+P352, P303+P361+P353, P321, P333+P313, P363, P370+P378, P403+P235, and P501|Aggregated GHS information provided by 2239 companies from 15 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H226: Flammable liquid and vapor [Warning Flammable liquids]|P210, P233, P240, P241, P242, P243, P280, P303+P361+P353, P370+P378, P403+P235, and P501

Excerpt from ERG Guide 128 [Flammable Liquids (Water-Immiscible)]: As an immediate precautionary measure, isolate spill or leak area for at least 50 meters (150 feet) in all directions. LARGE SPILL: Consider initial downwind evacuation for at least 300 meters (1000 feet). FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

SMALL SPILLS AND LEAKAGE: If you spill this chemical, use absorbent paper to pick up all liquid spill material. Your contaminated clothing and absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with alcohol followed by washing with a strong soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should store this chemical under refrigerated temperatures and away from mineral acids and bases. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

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

Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid breathing vapors, mist or gas. Remove all sources of ignition. Beware of vapors accumulating to form explosive concentrations. Vapors can accumulate in low areas.; Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.; Methods and materials for containment and cleaning up: Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and place in container for disposal according to local regulations.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

1,8-Cineole was present in groundwater samples at 8, 5, and 1 ug/L at distances of 5, 19, and 39 meters, respectively, down gradient of a landfill in Vejen, Denmark(1). 1,8-Cineole was identified not quantified in the leachate plum from a landfill in Norman, OK sampled in November 1995 and April 1996(2). 1,8-Cineole was on average only 1% of the total post treatment odor faction from a municipal waste treatment plant in China(3).

SOIL: 1,8-Cineole concentrations at 30, 50, and 70 cm soil depths at the Case Passerini landfill in Florence, Italy. Concentrations in 2 gas recovery wells were 5800 and 5750 ppbV(1).

INDOOR: 1,8-Cineole occurred at 15% and at a low concentration in indoor air of 50 normal houses - older than 3 years, no repairs done in the preceding 18 months, and residents had not complained of any symptoms related to sick building syndrome(1).|RURAL/REMOTE: 1,8-Cineole, together with l-limonene was present in nearly all air samples from an alpine forest region in Achenkirch, Tyrol, Austria, collected on June 14, 1996. Concentrations ranged from 0.18 to 0.73 ppb C(1).

1,8-Cineole emission rates from residential burning of southern-European woods(1).[Table#2658]|1,8-Cineole was detected at 37-60 ppb in chamber experiments on the reaction of ozone with a general purpose pine oil-based cleaner (ozone reaction rate constants were <1.5X10-19 cu cm/molec-sec). Ozone can be present in indoor air from intrusion of outdoor air and from office equipment and certain air purifiers. It was not a product of ozone reacting with an orange oil-based degreaser containing d-limonene as the sole active ingredient nor a plug-in scented-oil air freshener(1). The compound was detected not quantified as a volatile from wax paste for leather, liquid wax for floorings, and household detergents(2). 1,8-Cineole was detected not quantified in household kitchen waste exudate(3). The compound has been used in flavors for tobacco and tobacco smoke(4).|1,8-Cineole was present at 0.010 and 5.05 nL/L in emissions from alfalfa and cereal silage, respectively, on farms sampled in California's San Joaquin Valley(1). The compound was identified in liquid exudate from garden waste(2).

Oral, rat LD50: 2480 mg/kg|IDENTIFICATION AND USE: Cineole is an essential oil that is used as a fragrance or flavoring agent in: foods, candies, pharmaceutical aid (flavor), cough drops, and personal care products. It has a history of being used as an expectorant and an antiseptic. HUMAN EXPOSURE AND TOXICITY: Cineole is the main constituent of eucalyptus oil, and it is mainly used as a mucolytic agent in inflammatory airway diseases. ANIMAL STUDIES: A study was performed to assess the ocular irritancy potential of eucalyptol to the isolated bovine cornea. The corneas treated with eucalyptol were clear post treatment and had cloudy areas post incubation. Eucalyptol was considered not to be an ocular corrosive or severe irritant. Cineole was administered by gavage to three groups, each of five male and five female rats, for twenty-eight consecutive days, at dose levels of 30, 300 and 600 mg/kg bw/day. For both sexes at 300 and 600 mg/kg bw/day, examination of the liver revealed a dosage dependent incidence of centrilobular hypertrophy of the hepatocytes; no other indicators of liver damage were apparent. Following the two week recovery period, hypertrophy of hepatocytes was no longer present at 600 mg/kg bw/day for either sex. 1,8-Cineole induced accumulation of protein droplets in proximal tubular epithelial cells in male rats. The renal changes were specific to the male rat and of no toxicological relevance to man. Eucalyptol was tested as a constituent of toothpaste in an oral long-term study with mice. Groups of 52 male mice were given 0, 8 and 32 mg/kg bw/day eucalyptol in toothpaste base by gavage for 80 weeks followed by an observation period between 16 and 24 weeks. No treatment-related effects on body weight, food consumption, survival, weight of adrenals, kidneys, liver, lungs or spleen, or on the microscopic appearance of brain, lungs, liver and kidneys or on tumor incidence was observed.

Infant rats express conditioned responses to an odor experienced prenatally as a chemosensory cue associated with moderate alcohol intoxication. This study examined postnatal intake of a chemosensory cue (cineole) that had been paired with alcohol's unconditioned effects. It also tested the interaction between prenatal association and postnatal conditioning with cineole and alcohol. Pregnant female rats intubated with cineole were given ethanol (EtOH).25 or 4.0 hr later. Other groups received only water or water paired with ethanol. During postnatal day 15 (PD15), infant consumption of cineole solution was assessed. After the cineole drinking test, pups were intubated with EtOH or water to assess infant conditioning. On PD16, all pups were tested for mouthing to milk alone or to a milk-cineole solution. Statistical analysis confirmed fetal associative conditioning attributable to the unconditioned effects of prenatal alcohol. Fetuses given explicit pairings of cineole and alcohol ingested less cineole on PD15 than control fetuses given a 4-hr interval between cineole and alcohol. On PD16, consumption of cineole was significantly increased by prenatal exposure to cineole. Teratogenic effects of this dose of prenatal alcohol did not affect postnatal associative or nonassociative behavior. Prenatal associative learning can be established through temporal contiguity between fetal chemosensory stimulation and alcohol's unconditioned properties. This associative memory survives to infancy and modulates intake patterns and behavioral reactivity to substances that were prenatally paired with alcohol intoxication.|Cineole was administered by gavage to three groups, each of ten male and ten female Wistar Han (TM): RCCHan(TM): WIST strain rats, for up to eleven weeks (including a two week pre-pairing phase, pairing, gestation and early lactation for females) at dose levels of 30, 300 and 600 mg/kg bw/day. A control group of ten males and ten females was dosed with vehicle alone (Arachis oil BP). Clinical signs, bodyweight change, dietary intake and water consumption were monitored during the study. Pairing of animals within each dose group was undertaken on a one male: one female basis within each treatment group on Day 5 of the study, with females subsequently being allowed to litter and rear their offspring to Day 5 of lactation. An additional pairing for high dose females that failed to achieve pregnancy was performed to fully assess mating performance and fertility. During the lactation phase, daily clinical observations were performed on all surviving offspring, together with litter size and offspring weights and assessment of surface righting reflex. Adult males were terminated on Day 52 of the study following the completion of the second pairing at 600 mg/kg bw/day. Females and offspring were terminated on day 5 post partum. Any female which did not produce a pregnancy (unless allocated to a further mating phase) was terminated on or after Day 25 post coitum. All animals were subjected to a gross necropsy examination and histopathological evaluation of reproductive tissues was performed. Additional male organ weight and detailed histopathological examination of the testes were performed to more fully assess male fertility. Adult response: Mortality: There were no unscheduled deaths in the study. Clinical observations: Transient post-dosing salivation was observed from Day 7 at 600 mg/kg bw/day and Day 13 at 300 mg/kg bw/day. This sign was observed regularly throughout the treatment period with all animals being affected at both dosages, although the incidence of this finding was greatest at the high dosage. Transient post dosing salivation was also observed at 30 mg/kg bw/day for two females on Day 2 and one male on Day 50 of this study. Bodyweight: At 600 mg/kg bw/day body weight gain of males was statistically significantly lower than control during the first week of treatment. Subsequent body weight gains were considered to reflect normal biological varaition, but overall gain at termination remained lower than control. Bodyweight gain of males at 30 and 300 mg/kg bw/day and for females at all dosages, throughout the pre-pairing, gestation and lactation phases of the study, were considered to have been unaffected by treatment. Food consumption: Food consumption for both sexes was considered to have been unaffected by treatment throughout the study, and including gestation and lactation phases for females, at 30, 300 and 600 mg/kg bw/day. Food efficiency: At 600 mg/kg bw/day food conversation efficiency for males was lower than control during week 1; subsequent food utilisation was similar to control. Food conversation efficiency of males at 30 and 300 mg/kg bw/day and for females at all dosages, throughout the pre-pairing, gestation and lactation phases of the study, were considered to have been unaffected by the treatment. Reproductive performance: Mating: Pre-coital interval and mating evidence at the times of conception did not indicate any adverse effect of treatment on mating performance at 30, 300 and 600 mg/kg bw/day. Fertility: At 600 mg/kg bw/day, only seven females delivered a litter following the initial pairing but subsequent re-mating and additional assessment of male organ weight and detailed testicular histopathology did not indicate any treatment related effect on fertility for either sex. There was also no effect of treatment on fertility at 30 and 300 mg/kg bw/day. Gestation lengths: Gestation length was considered to be unaffected by treatment at 30, 300 and 600 mg/kg bw/day. Litter responses: Offspring litter size, sex ratio and viability: There was no effect of maternal treatment on corpora lutea and implantations counts, pre- and post-implantation loss, number of offspring born, sex ratio or subsequent survival to Day 4 of age at 30, 300 and 600 mg/kg bw/day. Offspring growth and development: At 600 mg/kg bw/day initial offspring body weight was similar to control but weight gain to Day 4 was statistically significantly lower than control. Mean offspring body weights, litter weight and weight gains to Day 4 of age were unaffected by maternal treatment at 30 and 300 mg/kg bw/day. Offspring observations: Assessment of surface righting ability on Day 1; offspring clinical signs and necropsy findings and did not indicate any effect of maternal treatment. Pathology: Necropsy: Macroscpoic necropsy findings did not indicate any effect of treatment at 30, 300 and 600 mg/kg bw/day. Organ weights: Male reproductive organ weights were unaffected by treatment at 30, 300 and 600 mg/kg bw/day and did not indicate any effect on fertility. Histopathology: Histopathological examinations did not indicate any effect of treatment at 600 mg/kg bw/day and these examinations, including detailed assessment of the spermatogenetic cycle for the testes did not indicate any effect on male fertility. Within the context of this study, the No Observed Adverse Effect Level (NOAEL) for adult toxicity, reproduction and offspring survival, growth and development was considered to be 600 mg/kg bw/day.

LD50 Rat dermal >2 g/kg bw|LD50 Rat female oral 4.3 g/kg bw|LD50 Rat male oral 4.7 g/kg bw|LD50 Rat oral 2480 mg/kg bw

1,8-Cineole is considered a major monoterpene emitted by vegetation into the atmosphere(1).|Its name is derived from its presence in essential oils of Eucalyptus globulus & Melaleuca leucadendron L (essential oil of cajeput). It was originally identified in the essential oil of Artemisia maritima and...in a large number (Approx 270) of other essential oils... the essential oil of Eucalyptus polibractea has been reported to contain up to 91% eucalyptol

1,8-Cineole's production and use as a fragrance and flavoring agent in foods, candies, cough drops, personal care products and pharmaceutical aid (flavor)(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 220(SRC), determined from a log Kow of 2.74(2) and a regression-derived equation(3), indicates that 1,8-cineole is expected to have moderate mobility in soil(SRC). Volatilization of 1,8-cineole from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.1X10-4 atm-cu m/mole(SRC), derived from its vapor pressure, 1.9 mm Hg(4), and water solubility, 3.5X10+3 mg/L(5). 1,8-Cineole is expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(5). Biodegradation data in soil were not available(SRC, 2015).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 220(SRC), determined from a log Kow of 2.74(2) and a regression-derived equation(3), indicates that 1,8-cineole is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(4) based upon an estimated Henry's Law constant of 1.1X10-4 atm-cu m/mole(SRC), derived from its vapor pressure, 1.9 mm Hg(5), and water solubility, 3.5X10+3 mg/L(6). Using this Henry's Law constant and an estimation method(4), volatilization half-lives for a model river and model lake are 13 hours and 8 days, respectively(SRC). According to a classification scheme(7), an estimated BCF of 30(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2015).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 1,8-cineole, which has a vapor pressure of 1.9 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase cineole 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 1.4 days, calculated from its rate constant of 1.11X10-11 cu cm/molecule-sec at 25 °C(3). 1,8-Cineole does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of 1,8-cineole with photochemically-produced hydroxyl radicals is 1.11X10-11 cu cm/molecule-sec at 25 °C(1). This corresponds to an atmospheric half-life of about 1.4 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of 1,8-cineole with nitrate radicals is 1.75X10-16 cu cm/molecule-sec at 25 °C(2). This corresponds to an atmospheric half-life of about 7.8 years at an atmospheric concentration of 2.4X10+7 molecules per cu cm(1). 1,8-Cineole is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). 1,8-Cineole 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 30 was calculated in fish for 1,8-cineole(SRC), using a log Kow of 2.74(1) and a regression-derived equation(2). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of 1,8-cineole is estimated as 220(SRC), using a log Kow of 2.74(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that 1,8-cineole is expected to have moderate mobility in soil. In soil infiltration studies using secondary effluent from Fort Polk, LA collected Nov 4-5 1980, 1,8-cineole, present at 0.091 ug/L, was not detected in column fluid effluents on the second inundation cycle(4).

The Henry's Law constant for 1,8-cineole is estimated as 1.1X10-4 atm-cu m/mole(SRC) derived from its vapor pressure, 1.90 mm Hg(1), and water solubility, 3.5X10+3 mg/L(2). This Henry's Law constant indicates that cineole is expected to volatilize from water surfaces(3). 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)(3) is estimated as 13 hours(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(3) is estimated as 8 days(SRC). 1,8-Cineole's estimated Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). The potential for volatilization of 1,8-cineole from dry soil surfaces may exist(SRC) based upon the vapor pressure(1).

SURFACE WATER: 1,8-Cineole was present at a concentration of 3.4 ng/L in a water samples from Resurrection Bay, south-central coast of Alaska, collected June 17, 1986. It was not detected in a sample collected June 25, 1985(1).

1,8-Cineole was identified as a volatile odor component released from cooking full-fat and reduced fat frankfurters. Mean relative peaks (1 ng bromobenznene = 100) were 1290, 1830 and 1870 for 30%, 12% and 5% fat, respectively(1). The compound was present as 0.18% of volatiles identified from edible Korean chamchwi (Aster scaber)(2). Concentrations in mature and ripe guava (Psidium guajava Linn) fruit volatiles were 30,954 and 7,238 ug/kg, respectively(3).

ENVIRONMENTAL: 1,8-Cineole was detected not quantified in mother's milk samples collected in 1978 from residents of Jersey City, NJ. It was not detected in samples from Bayonne, NJ, Pittsburgh, PA, Baton Rouge, LA, or Charleston WV(1).

According to the 2012 TSCA Inventory Update Reporting data, 3 reporting facilities estimate the number of persons reasonably likely to be exposed during the manufacturing, processing, or use of 1,8-cineole in the United States may be as low as 50 workers and as high as 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 83,399 workers (20,158 of these are female) were potentially exposed to 1,8-cineole in the US(1). Occupational exposure to 1,8-cineole may occur through inhalation and dermal contact with this compound at workplaces where 1,8-cineole is produced or used. Monitoring data indicate that the general population may be exposed to 1,8-cineole via inhalation of ambient air and food odors, and dermal contact with consumer products containing 1,8-cineole(SRC).

1,8-Cineole was detected not quantified in mother's milk samples collected in 1978 from residents of Jersey City, NJ. It was not detected in samples from Bayonne, NJ, Pittsburgh, PA, Baton Rouge, LA, or Charleston WV(1).

/EXPL THER/ Cineole has mucolytic, bronchodilating and anti-inflammatory properties and reduces the exacerbation rate in patients suffering from COPD, as well as ameliorates symptoms in patients suffering from asthma and rhinosinusitis. Based on these effects, we therefore postulated the hypothesis that patients with acute bronchitis would also benefit from therapy with Cineole. As part of a double-blind, placebo-controlled, multi-center-study, a total of 242 patients with confirmed acute bronchitis was randomly selected to participate. Over a period of 10 days, all patients were administered 3 x 200 mg of Cineole, or a respective placebo, per day. The primary outcome measure was a Bronchitis Sum Score, which summarizes the relevant symptoms of acute bronchitis. After 4 days of treatment it was notable, that the patient group treated with Cineole, showed significantly more improvements of the bronchitis-sum-score than those of the placebo group (p?=?0.0383). The statistical significant difference of the individual outcome measures was especially underlined by the frequency of cough fits by p?=?0.0001 after 4 days. The effects of Cineole in the treatment of acute bronchitis were clearly measurable and could be proven after a treatment period of merely 4 days. This study corroborates the fact that Cineole actively and significantly reduces cough frequency after four days. ...|/EXPL THER/ The clinical effects of mucolytics in patients with chronic obstructive pulmonary disease (COPD) are discussed controversially. Cineole is the main constituent of eucalyptus oil and mainly used in inflammatory airway diseases as a mucolytic agent. We hypothesized that its known mucolytic, bronchodilating and anti-inflammatory effects as concomitant therapy would reduce the exacerbation rate and show benefits on pulmonary function tests as well as quality of life in patients with COPD. In this double-blind, placebo-controlled multi-center-study we randomly assigned 242 patients with stable COPD to receive 200 mg of cineole or placebo 3 times daily as concomitant therapy for 6 months during winter-time. The frequency, duration and severity of exacerbations were combined as primary outcome measures for testing as multiple criteria. Secondary outcome measures included changes of lung function, respiratory symptoms and quality of life as well as the single parameters of the exacerbations. Baseline demographics, lung function and standard medication of both groups were comparable. During the treatment period of 6 months the multiple criteria frequency, severity and duration of exacerbations were significantly lower in the group treated with cineole in comparison to placebo. Secondary outcome measures validated these findings. Improvement of lung function, dyspnea and quality of life as multiple criteria were statistically significant relative to placebo. Adverse events were comparable in both groups. Concomitant therapy with cineole reduces exacerbations as well as dyspnea and improves lung function and health status. This study further suggests cineole as an active controller of airway inflammation in COPD by intervening in the pathophysiology of airway inflammation of the mucus membrane.

Agents that suppress cough. They act centrally on the medullary cough center. EXPECTORANTS, also used in the treatment of cough, act locally. (See all compounds classified as Antitussive Agents.)|Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. (See all compounds classified as Anti-Infective Agents.)|Substances added to foods and medicine to improve the taste. (See all compounds classified as Flavoring Agents.)|Substances causing insects to turn away from them or reject them as food. (See all compounds classified as Insect Repellents.)|Liquids that dissolve other substances (solutes), generally solids, without any change in chemical composition, as, water containing sugar. (Grant and Hackh's Chemical Dictionary, 5th ed) (See all compounds classified as Solvents.)|Solutions for rinsing the mouth, possessing cleansing, germicidal, or palliative properties. (From Boucher's Clinical Dental Terminology, 4th ed) (See all compounds classified as Mouthwashes.)

The biotransformation of 1,8-cineole was investigated using human liver microsomes. The metabolite was established as 2-exo-hydroxy-1,8-cineole. 1,8-cineole 2-hydroxylation catalyzed by human liver microsomes was found to be efficiently conducted.|Cineole was administered to male rats once daily by gastric intubation for 20 days. Urine was collected and major metabolites identified as methyl ester of 1,8-dihydroxy-10-carboxy p-methane, 2-hydroxy cineole and 3-hydroxy cineole.|Nature of non-conjugated metabolites of 1,8-cineole in urine and feces of brushtail possum yield p-cresol, 9-hydroxycineole and cineol-9-oic acid.|1,8-Cineole has known human metabolites that include 2alpha-hydroxy-1,8-cineole and 3alpha-hydroxy-1,8-cineole.

SYMPTOMS: The symptoms associated with this compound include: epigastric burning with nausea and usually vomiting; vertigo; ataxia; muscle weakness; stupor; pallor; and sometimes - cyanosis, respiratory stridor and miosis. Delirium and occasionally convulsions may occur. Symptoms may be delayed for 24 hours, rarely. ACUTE/CHRONIC HAZARDS: This compound may cause irritation on contact. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

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. /Camphor and Related Compounds/|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. Anticipate seizures and minimize all external stimuli. Treat seizures as necessary ... . Monitor for shock and treat as 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 ... . /Camphor and Related Compounds/|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. Monitor and treat cardiac 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 ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Camphor and Related Compounds/

/ALTERNATIVE and IN VITRO TESTS/ The purpose of this test was to evaluate the skin irritation potential of eucalyptol using the EPISKIN (TM) reconstructed human epidermis model after a treatment period of 15 minutes followed by a post-exposure incubation period of 42 hours. The principle of the assay was based on the measurement of cytotoxicity in reconstructed human epidermal cultures following topical exposure to eucalyptol by means of the colorimetric MTT reduction assay. Cell viability is measured by enzymatic reduction of the yellow MTT tetrazolium salt (3 -[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) to a blue formazan salt (within the mitochondria of viable cells) in the eucalyptol treated tissues relative to the negative controls. The concentration of the inflammatory mediator IL-1a in the culture medium retained following the 42-hour post-exposure incubation period is also determined for eucalyptol which are found to be borderline non-irritant based upon the MTT reduction endpoint. This complimentary end-point will be used to either confirm a non-irritant result or will be used to override the non-irritant result. This method was designed to be compatible with the following: OECD Guidelines for the Testing of Chemicals No. 439 In VitroSkin Irritation (adopted 22 July 2010) Method B.46 of Commission Regulation (EC) No. 440/2008/EC Triplicate tissues were treated with eucalyptol for an exposure period of 15 minutes. At the end of the exposure period each tissue was rinsed before incubating for 42 hours. At the end of the post-exposure incubation period each tissue was taken for MTT-loading. The maintenance medium from beneath each tissue was transferred to pre-labelled micro tubes and stored in a freezer for possible inflammatory mediator determination. After MTT loading a total biopsy of each epidermis was made and placed into micro tubes containing acidified isopropanol for extraction of formazan crystals out of the MTT-loaded tissues. At the end of the formazan extraction period each tube was mixed thoroughly and duplicate 200 ul samples were transferred to the appropriate wells of a pre-labelled 96 -well plate. The optical density was measured at 540 nm. Data are presented in the form of percentage viability (MTT reduction in the test item treated tissues relative to negative control tissues). The relative mean viability of the test item treated tissues was 88.9% after the 15-Minute exposure period. The quality criteria required for acceptance of results in the test were satisfied. Eucalyptol was considered to be Non-Irritant (NI).

1,8 Cineol

Grades: Technical; National Formulary.|Technical grade ... purity of 99.6 - 99.8%

All other chemical product and preparation manufacturing|2-Oxabicyclo[2.2.2]octane, 1,3,3-trimethyl-: ACTIVE|1,8-cineole is produced only from natural sources as these are sufficiently inexpensive to make synthesis uneconomic. Originally, it was produced from Cajeput oil, but the discovery of Eucalyptus globulus, the oil of which contains up to 95% 1,8-cineole, in 1788 led to the first commercial production from that source in 1854 in Australia, and then to its taking over as the dominant source. ... Much of the oil is used per se and only about one-quarter of it is distilled to produce pure cineole.|The chief constituent of oil of eucalyptus; also found in essential oils of laurel, rosemary, and many other aromatic plants.

EPA Safer Chemical Functional Use Classes -> Fragrances|Safer Chemical Classes -> Yellow triangle - The chemical has met Safer Choice Criteria for its functional ingredient-class, but has some hazard profile issues|Food additives -> Flavoring Agents|Lipids -> Prenol Lipids [PR] -> Isoprenoids [PR01] -> C10 isoprenoids (monoterpenes) [PR0102]|Cosmetics -> Denaturant; Masking; Tonic

Flavoring Agents