Isoborneol

154.25

154.25

4126091

204-712-4

DTXSID2042060

White solid|Tablets from petroleum ether

29061900

20.2

3.24 (LogP)

Yellow Powder

0.9867 g/cm³ @ Temp: 20 °C

213 °C

76-77 °C @ Press: 3 Torr

200 °F

1.4710 (estimate)

insoluble

2-8°C

5.02X10-2 mm Hg at 25 °C

Piney, camphor-like odor

Burning taste somewhat reminiscent of mint

Henry's Law constant = 6.70X10-6 atm-cu m/mol at 25 °C (est)

Geometrical isomer of borneol|Insoluble in water; very soluble in ethanol; diethyl ether, benzene /Borneol (+/-)/|Hydroxyl radical reaction rate constant = 1.14X10-11 cu cm/mole-sec at 25 °C (est)

Ⅲ

4.1

UN 1312 4.1/PG 3

2

11-38

24/25

NP7300000

F,Xi

Stable under recommended storage conditions.

P210

H228-H315

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: Burn in a chemical incinerator equipped with an afterburner and scrubber but exert extra care in igniting as this material is highly flammable. Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Contaminated packaging: Dispose of as unused product.

Synthetic flavoring substances and adjuvants may be safely used in food 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. (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. Isoborneol is included on this list.

Api AM et al; RIFM fragrance ingredient safety assessment, Isoborneol, CAS Registry Number 124-76-5. Food Chem Toxicol 84 (Suppl) :S33-41 (2015)

|Warning|H228 (99.56%): Flammable solid [Danger Flammable solids]|P210, P240, P241, P280, and P370+P378|Aggregated GHS information provided by 1609 companies from 8 notifications to the ECHA C&L Inventory.|H228: Flammable solid [Danger Flammable solids]|P210, P240, P241, P264, P280, P302+P352, P321, P332+P313, P362, and P370+P378

Skin protection: Handle with gloves.|Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).|Body Protection: Impervious clothing. Flame retardant antistatic protective clothing., The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.|Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

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

Special hazards arising from the substance or mixture: Carbon oxides

ACCIDENTAL RELEASE MEASURES; Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. Evacuate personnel to safe areas. Avoid breathing dust. 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: Sweep up and shovel. Contain spillage, and then collect with an electrically protected vacuum cleaner or by wetbrushing and place in container for disposal according to local regulations. Keep in suitable, closed containers for disposal. Contain spillage, pick up with an electrically protected vacuum cleaner or by wet-brushing and transfer to a container for disposal according to local regulations.

Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed. Keep away from sources of ignition - No smoking. Take measures to prevent the build up of electrostatic charge.|ACCIDENTAL RELEASE MEASURES; Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.|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.|Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.|For more Preventive Measures (Complete) data for Isoborneol (6 total), please visit the HSDB record page.

A skin irritant.

Isoborneol was not detected (above the method detection limit of 500 ng/L) in effluent samples collected from a municipal waste water treatment facility near Phoenix AZ, sampling dates were between May and June 2001(1).

SEDIMENT: In a comprehensive literature review (1997-2008) of 80 sources on environmental analysis of chemicals in the Great Lakes Basin, isoborneol was not detected in wastewater sediments at concentrations above the reporting limit of 12.5 ng/g(1).

Isoborneol has been identified as a constituent of tobacco smoke(1).

IDENTIFICATION AND USE: Isoborneol is a white solid. It is used as a flavor ingredient in food and beverages. It is also used in perfumery and in preparation of chemical esters.HUMAN STUDIES: In a human maximization test, no reactions indicative of sensitization were observed with 10% isoborneol in petrolatum. Isoborneol did not exhibit significant cytotoxicity at concentrations ranging between 0.016% and 0.08% when tested against human cell lines. ANIMAL STUDIES: Isoborneol did not exhibit significant cytotoxicity at concentrations ranging between 0.016% and 0.08% when tested against monkey cell lines. Read across chemicals l-borneol and isobornyl acetate were evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity. In the13-week subchronic toxicity study for isobornyl acetate conducted in rats the NOEL was determined to be 15 mg/kg/day, based on increased urinary cell excretion.The NOAEL for reproductive toxicity in the parental generation was determined to be 300 mg/kg/day for isobornyl acetate. l-borneol was not mutagenic in the Ames test. Isoborneol, was assessed for genotoxic potential in the Bluescreen assay and was found negative for genotoxicity and cytotoxicity in the presence and absence of metabolic activation.

Oxidative stress caused by dopamine (DA) may play an important role in the pathogenesis of Parkinson's disease (PD). (+/-) Isoborneol is a monoterpenoid alcohol present in the essential oils of numerous medicinal plants and is a known antioxidant. In this study, we investigated the neuroprotective effect of isoborneol against 6-hydroxydopamine (6-OHDA)-induced cell death in human neuroblastoma SH-SY5Y cells. Pretreatment of SH-SY5Y cells with isoborneol significantly reduced 6-OHDA-induced generation of reactive oxygen species (ROS) and 6-OHDA-induced increases in intracellular calcium. Furthermore, apoptosis induced by 6-OHDA was reversed by isoborneol treatment. Isoborneol protected against 6-OHDA-induced increases in caspase-3 activity and cytochrome C translocation into the cytosol from mitochondria. Isoborneol prevented 6-OHDA from decreasing the Bax/Bcl-2 ratio. We also observed that isoborneol decreased the activation of c-Jun N-terminal kinase and induced activation of protein kinase C (PKC) which had been suppressed by 6-OHDA. Our results indicate that the protective function of isoborneol is dependent upon its antioxidant potential and strongly suggest that isoborneol may be an effective treatment for neurodegenerative diseases associated with oxidative stress.

LD50 Mice oral 3720 mg/kg /l-form/|LD50 Mice oral 4960 mg/kg /d-form/|LD50 Mice oral 3830 mg/kg /dl-form/|LD50 Rat oral 5200 mg/kg|LD50 Mice iv 56 mg/kg

Isoborneol is a constituent of various plant parts, tissues, and essential oils of a variety of plant species(1). The compound is reported as found in the oil of Abies sibirca and a few other essences and in the essential oil from roots of Chamaeciparis formosensis(1). Isoborneol is also reported as found in apple, papaya, blackberry, cinnamompm, ginger, thymus, cheeses, cognac, mile oil, eucalyptus oil and mastic gum leaf oil(2).

Isoborneol's production and use in perfumery and for the production of chemical esters(1), and as a flavoring agent(2) may result in its release to the environment through various waste streams(SRC). Its previous use as an insecticide(3) may have resulted in its direct release to the environment(SRC). Isoborneol has been identified as a constituent of tobacco smoke(4).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 200(SRC), determined from a log Kow of 3.24(2) and a regression-derived equation(3), indicates that isoborneol is expected to have moderate mobility in soil(SRC). Volatilization of isoborneol from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 6.7X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Isoborneol has an estimated vapor pressure of 3.5X10-2 mm Hg(SRC), determined from a fragment constant method(3) and exists as a liquid under environmental conditions; therefore, isoborneol may volatilize from dry soil(SRC). Based on analogy to borneol, isoborneol is expected to biodegrade rapidly. Borneol reached 97% of theoretical BOD using activated sludge in the Japanese MITI test(5) which suggests that biodegradation is an important environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 200(SRC), determined from a log Kow of 3.24(2) and a regression-derived equation(3), indicates that isoborneol may adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(4) based upon an estimated Henry's Law constant of 6.7X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). Using this Henry's Law constant and an estimation method(4), volatilization half-lives for a model river and model lake are 7 days and 54 days, respectively(SRC). According to a classification scheme(6), an estimated BCF of 64(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Based on analogy to borneol, isoborneol is expected to biodegrade rapidly. Borneol reached 97% of theoretical BOD using activated sludge in the Japanese MITI test(7) which suggests that biodegradation is an important environmental fate process in water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), isoborneol, which has an estimated vapor pressure of 3.5X10-2 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase isoborneol 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 34 hours(SRC), calculated from its rate constant of 1.1X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Isoborneol 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 isoborneol with photochemically-produced hydroxyl radicals has been estimated as 1.1X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 34 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Isoborneol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Isoborneol 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 64 was calculated in fish for isoborneol(SRC), using a log Kow of 3.24(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).

The Koc of isoborneol is estimated as 200(SRC), using a log Kow of 3.24(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that isoborneol is expected to have moderate mobility in soil(SRC).

The Henry's Law constant for isoborneol is estimated as 6.7X10-6 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that isoborneol 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 7 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 54 days(SRC). Isoborneol's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). Isoborneol has an estimated vapor pressure of 3.5X10-2 mm Hg at 25 °C(SRC), determined from a fragment constant method(1) and exists as a liquid under environmental conditions; therefore, isoborneol may volatilize from dry soil(SRC).

SURFACE WATER: Isoborneol was not detected (above the method detection limit of 500 ng/L) in water samples collected from the Assunpink Creek watershed near Trenton NJ, sampling dates not provided(1). Water samples collected from 23 streams located in Iowa were examined under low- (n = 23), normal- (n = 23), and high-flow (n = 30) conditions, isoborneol was not detected in low-, and high-flow samples, but was detected in normal-flow samples at a maximum concentration of 0.12 ug/L with a detection frequency of 4.3%(2). Isoborneol was not detected in 24 stream and raw water samples collected in November and December 2001 at select locations across the US(3).

Isoborneol has been reported found in cognac and cheeses(1).

Isoborneol has been reported found in cheeses(1).

According to the 2016 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 isoborneol in the United States may be as low as 25 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 13,463 workers (8,811 of these are female) were potentially exposed to isoborneol in the US(1). Occupational exposure to isoborneol may occur through inhalation and dermal contact with this compound at workplaces where isoborneol is produced or used. Limited monitoring and use data indicate that the general population may be exposed to isoborneol via ingestion of food and dermal contact with plant essential oils and consumer products containing isoborneol.

/EXPL THER/ Isoborneol, a monoterpene and a component of several plant essential oils, showed dual viricidal activity against herpes simplex virus 1 (HSV-1). First, it inactivated HSV-1 by almost 4 log10 values within 30 min of exposure, and second, isoborneol at a concentration of 0.06% completely inhibited viral replication, without affecting viral adsorption. Isoborneol did not exhibit significant cytotoxicity at concentrations ranging between 0.016% and 0.08% when tested against human and monkey cell lines. Isoborneol specifically inhibited glycosylation of viral polypeptides based on the following data: (1) the mature fully glycosylated forms of two viral glycoproteins gB and gD were not detected when the virus was replicated in the presence of isoborneol, (2) no major changes were observed in the glycosylation pattern of cellular polypeptides between untreated and isoborneol treated Vero cells, (3) isoborneol did not affect the glycosylation of gB produced from a copy of the gB gene resident in the cellular genome, and (4) other monoterpenes such as 1,8-cineole and borneol, a stereoisomer of isoborneol, did not inhibit HSV-1 glycosylation.

The percutaneous absorptions of camphene, isoborneol-acetate, limonene, menthol and alpha-pinene as constituents of a foam bath (Pinimenthol) were measured on animals using radioactively labeled ingredients. Pharmacokinetic measurements showed maximum blood levels for all tested ingredients 10 min after the onset of percutaneous absorption. None of the ingredients was preferentially absorbed. Blood levels of all ingredients after 10 min of percutaneous absorption were a direct function of the size of the skin area involved.

/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 if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the 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. /Poisons A and B/|/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 needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock 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 ... . /Poisons A and B/|/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 ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /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. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ In a human maximization test, no reactions indicative of sensitization were observed with 10% isoborneol in petrolatum.|/GENOTOXICITY/ The clastogenic potential of the read across material, l-borneol, was assessed in a GLP compliant in vitro micronucleus study conducted in accordance with OECD TG 487. Human peripheral blood lymphocytes were exposed to varying concentrations of l-borneol in DMSO up to 600 mg/mL for 4 hr, with and without metabolic activation and up to 55 mg/mL for 24 hr without metabolic activation. A significant, non-dose-dependent increase in micronucleated binucleated (MNBN) cells was increased compared to vehicle control in the non-S9-activated 4 hr exposure group at doses of 100 and 400 mg/mL. However, the percentage of MNBN cells was within the historical solvent control range; this increase was not considered biologically relevant. Under the conditions of the study, l-borneol was concluded to be negative for the induction of micronuclei in the micronucleus test. /l-borneol/|/ALTERNATIVE and IN VITRO TESTS/ ... Isoborneol did not exhibit significant cytotoxicity at concentrations ranging between 0.016% and 0.08% when tested against human and monkey cell lines.

borneol

All other chemical product and preparation manufacturing|Bicyclo[2.2.1]heptan-2-ol, 1,7,7-trimethyl-, (1R,2R,4R)-rel-: ACTIVE|Borneol is an endo isomer; the corresponding exo isomer is isoborneol|Natural occurrence: Ashanti pepper (Piper guineense Schum and Thom) Ginger (Zingiber species) Grape brandy Camomile Honey Cheese, various types Mastic (Pistacia lentiscus) Cinnamomum species Ocimum species Curcuma species Papaya (Carica papaya L.) Eucalyptus oil (Eucalyptus globulus Labill) Raspberry, blackberry and boysenberry Rooibos tea (Aspalathus linearis) Salvia species Rosemary (Rosmarinus officinalis L.) Thyme (Thymus species)

Method: USGS-NWQL O-1433-01; Procedure: gas chromatography/mass spectrometry; Analyte: isoborneol; Matrix: filtered wastewater and natural-water samples; Detection Limit: 0.11 ug/L.|Method: USGS-NWQL O-4433-06; Procedure: continuous liquid-liquid extractor with gas chromatography with mass spectrometry detection; Analyte: isoborneol; Matrix: whole wastewater and environmental water samples; Detection Limit: 0.05 ug/L.|Gas chromatography (GC)-NMR method is described for detecting isoborneol in commercial borneol preparations.|Isoborneol detected by chromatographic analysis with previous absorption. Determination was made by internal reference method with naphthalene as reference.|Resolution of chiral compounds has played an important role in the pharmaceutical field, involving detailed studies of pharmacokinetics, physiological, toxicological, and metabolic activities of enantiomers. Herein, a reliable method by high-performance liquid chromatography (HPLC) coupled with an optical rotation detector was developed to separate isoborneol enantiomers. A cellulose tris(3, 5-dimethylphenylcarbamate)-coated chiral stationary phase showed the best separation performance for isoborneol enantiomers in the normal phase among four polysaccharide chiral packings. The effects of alcoholic modifiers and column temperature were studied in detail. Resolution of the isoborneol racemate displayed a downward trend along with an increase in the content of ethanol and column temperature, indicating that less ethanol in the mobile phase and lower temperature were favorable to this process. Moreover, two isoborneol enantiomers were obtained via a semipreparative chiral HPLC technique under optimum conditions, and further characterized by analytical HPLC, and experimental and calculated vibrational circular dichroism (VCD) spectroscopy, respectively. The solution VCD spectrum of the first-eluted component was consistent with the Density Functional Theory (DFT) calculated pattern based on the SSS configuration, indicating that this enantiomer should be (1S, 2S, 4S)-(+)-isoborneol. Briefly, these results have provided reliable information to establish a method for analysis, preparative separation, and absolute configuration of chiral compounds without typical chromophoric groups.

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