rel-(1S*,4β*)-1,7,7-トリメチルビシクロ[2.2.1]ヘプタン-2α*-オール

White to off-white crystals

White translucent lumps

In water, 738 mg/L at 25 °C

Slightly soluble in propylene glycol

Soluble in alcohol and ether

Slightly soluble in proylene glycol; Very slightly soluble in water; Insoluble in vegatable oils

Soluble (in ethanol)

202 °C

Hexanogal plates from petroleum ether; melting point: 204 °C; boiling point: 210 °C at 779 mm Hg /L-Borneol/

0.03 [mmHg]

5.02X10-2 mm Hg at 25 °C

Specific optical rotation: +37.7 deg at 20 °C/D (alc, 5%), specific optical rotation: +44.4 deg at 22 °C/546 (toluene, 0.5%) /D-Borneol/

Specific optical rotation: -37.7 deg at 20 °C/D (alc, 5%); -44.4 deg at 22 °C/546 (toluene, 0.5%) /L-Borneol/

Borneol appears as a white colored lump-solid with a sharp camphor-like odor. Burns readily. Slightly denser than water and insoluble in water. Used to make perfumes.

Liquid

White translucent solid; [Hawley]

White to off-white crystals; piney camphoraceous aroma

Danger

H228 (99%): Flammable solid [Danger Flammable solids]

P210, P240, P241, P280, and P370+P378 (click each P-code to see the statement)

Aggregated GHS information provided per 1875 reports by companies from 14 notifications to the ECHA C&L Inventory.；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

Not Classified

Chemical: Bicyclo[2.2.1]heptan-2-ol, 1,7,7-trimethyl-, endo-

Regulation (EC) No 1831/2003 (amended)

Bicyclo[2.2.1]heptan-2-ol, 1,7,7-trimethyl-, (1R,2S,4R)-rel- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Bicyclo[2.2.1]heptan-2-ol, 1,7,7-trimethyl-, (1R,2S,4R)-rel- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 13-07-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/24601

Bicyclo[2.2.1]heptan-2-ol, 1,7,7-trimethyl-, (1R,2S,4R)-rel-: Does not have an individual approval but may be used under an appropriate group standard

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

Excerpt from ERG Guide 133 [Flammable Solids]:；Flammable/combustible material. May be ignited by friction, heat, sparks or flames. Some may burn rapidly with flare-burning effect. Powders, dusts, shavings, borings, turnings or cuttings may explode or burn with explosive violence. Substance may be transported in a molten form at a temperature that may be above its flash point. May re-ignite after fire is extinguished. (ERG, 2024)

· Flammable/combustible material.；· May be ignited by friction, heat, sparks or flames.；· Some may burn rapidly with flare-burning effect.；· Powders, dusts, shavings, borings, turnings or cuttings may explode or burn with explosive violence.；· Substance may be transported in a molten form at a temperature that may be above its flash point.；· May re-ignite after fire is extinguished.

Excerpt from ERG Guide 133 [Flammable Solids]:；Fire may produce irritating and/or toxic gases. Contact may cause burns to skin and eyes. Contact with molten substance may cause severe burns to skin and eyes. Runoff from fire control or dilution water may cause environmental contamination. (ERG, 2024)

· Fire may produce irritating and/or toxic gases.；· Contact may cause burns to skin and eyes.；· Contact with molten substance may cause severe burns to skin and eyes.；· Runoff from fire control or dilution water may cause environmental contamination.

Borneol 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.

BORNEOL is an alcohol. Flammable and/or toxic gases are generated by the combination of alcohols with alkali metals, nitrides, and strong reducing agents. They react with oxoacids and carboxylic acids to form esters plus water. Oxidizing agents convert them to aldehydes or ketones. Alcohols exhibit both weak acid and weak base behavior. They may initiate the polymerization of isocyanates and epoxides.

/GUIDE 133 FLAMMABLE SOLIDS/ Fire or Explosion: Flammable/combustible material. May be ignited by friction, heat, sparks or flames. Some may burn rapidly with flare burning effect. Powders, dusts, shavings, borings, turnings or cuttings may explode or burn with explosive violence. Substance may be transported in a molten form at a temperature that may be above its flash point. May re-ignite after fire is extinguished.

/GUIDE 133 FLAMMABLE SOLIDS/ Health: Fire may produce irritating and/or toxic gases. Contact may cause burns to skin and eyes. Contact with molten substance may cause severe burns to skin and eyes. Runoff from fire control may cause pollution.

/GUIDE 133 FLAMMABLE SOLIDS/ Public Safety: CALL Emergency Response Telephone Number on Shipping Paper first. If Shipping Paper not available or no answer, refer to appropriate telephone number listed on the inside back cover. As an immediate precautionary measure, isolate spill or leak area for at least 25 meters (75 feet) in all directions. Keep unauthorized personnel away. Stay upwind. Keep out of low areas.

/GUIDE 133 FLAMMABLE SOLIDS/ Protective Clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Structural firefighters' protective clothing will only provide limited protection.

For more DOT Emergency Guidelines (Complete) data for BORNEOL (8 total), please visit the HSDB record page.

Borneol

UN1312

Div 4.1 Flammable solid (49 eCFR § 173.124)

PG III: the degree of danger presented by the material is minor；For more information about the packing group assignment, please visit 49 eCFR § 173

Excerpt from ERG Guide 133 [Flammable Solids]:；SMALL FIRE: Dry chemical, CO2, sand, earth, water spray or regular foam.；LARGE FIRE: Water spray, fog or regular foam. If it can be done safely, move undamaged containers away from the area around the fire.；FIRE INVOLVING METAL PIGMENTS OR PASTES (E.G. "ALUMINUM PASTE"): Aluminum Paste fires should be treated as a combustible metal fire. Use DRY sand, graphite powder, dry sodium chloride-based extinguishers or class D extinguishers. Also, see ERG Guide 170.；FIRE INVOLVING TANKS, RAIL TANK CARS OR HIGHWAY TANKS: Cool containers with flooding quantities of water until well after fire is out. For massive fire, use unmanned master stream devices or monitor nozzles; if this is impossible, withdraw from area and let fire burn. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from tanks in direct contact with flames. (ERG, 2024)

· CALL 911. Then call emergency response telephone number on shipping paper. If shipping paper not available or no answer, refer to appropriate telephone number listed on the inside back cover.；· Keep unauthorized personnel away.；· Stay upwind, uphill and/or upstream.

· ELIMINATE all ignition sources (no smoking, flares, sparks or flames) from immediate area.；· Do not touch or walk through spilled material.；Small Dry Spill；· With clean shovel, place material into clean, dry container and cover loosely; move containers from spill area.；Large Spill；· Wet down with water and dike for later disposal.；· Prevent entry into waterways, sewers, basements or confined areas.

Excerpt from ERG Guide 133 [Flammable Solids]:；Refer to the "General First Aid" section. Specific First Aid: Removal of solidified molten material from skin requires medical assistance. (ERG, 2024)

General First Aid:；· Call 911 or emergency medical service.；· Ensure that medical personnel are aware of the material(s) involved, take precautions to protect themselves and avoid contamination.；· Move victim to fresh air if it can be done safely.；· Administer oxygen if breathing is difficult.；· If victim is not breathing:；-- DO NOT perform mouth-to-mouth resuscitation; the victim may have ingested or inhaled the substance.；-- If equipped and pulse detected, wash face and mouth, then give artificial respiration using a proper respiratory medical device (bag-valve mask, pocket mask equipped with a one-way valve or other device).；-- If no pulse detected or no respiratory medical device available, provide continuous compressions. Conduct a pulse check every two minutes or monitor for any signs of spontaneous respirations.；· Remove and isolate contaminated clothing and shoes.；· For minor skin contact, avoid spreading material on unaffected skin.；· In case of contact with substance, remove immediately by flushing skin or eyes with running water for at least 20 minutes.；· For severe burns, immediate medical attention is required.；· Effects of exposure (inhalation, ingestion, or skin contact) to substance may be delayed.；· Keep victim calm and warm.；· Keep victim under observation.；· For further assistance, contact your local Poison Control Center.；· Note: Basic Life Support (BLS) and Advanced Life Support (ALS) should be done by trained professionals.；Specific First Aid:；· Removal of solidified molten material from skin requires medical assistance.

Excerpt from ERG Guide 133 [Flammable Solids]:；ELIMINATE all ignition sources (no smoking, flares, sparks or flames) from immediate area. Do not touch or walk through spilled material.；SMALL DRY SPILL: With clean shovel, place material into clean, dry container and cover loosely; move containers from spill area.；LARGE SPILL: Wet down with water and dike for later disposal. Prevent entry into waterways, sewers, basements or confined areas. (ERG, 2024)

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.

Excerpt from ERG Guide 133 [Flammable Solids]:；IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area for at least 25 meters (75 feet) in all directions.；LARGE SPILL: Consider initial downwind evacuation for at least 100 meters (330 feet).；FIRE: If tank, rail tank car or highway tank 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, 2024)

Immediate precautionary measure；· Isolate spill or leak area for at least 25 meters (75 feet) in all directions.；Large Spill；· Consider initial downwind evacuation for at least 100 meters (330 feet).；Fire；· If tank, rail tank car or highway tank 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.

Small Fire；· Dry chemical, CO2, sand, earth, water spray or regular foam.；Large Fire；· Water spray, fog or regular foam.；· If it can be done safely, move undamaged containers away from the area around the fire.；Fire Involving Metal Pigments or Pastes (e.g. "Aluminum Paste")；· Aluminum Paste fires should be treated as a combustible metal fire. Use DRY sand, graphite powder, dry sodium chloride-based extinguishers or class D extinguishers. Also, see GUIDE 170.；Fire Involving Tanks, Rail Tank Cars or Highway Tanks；· Cool containers with flooding quantities of water until well after fire is out.；· For massive fire, use unmanned master stream devices or monitor nozzles; if this is impossible, withdraw from area and let fire burn.；· Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank.；· ALWAYS stay away from tanks in direct contact with flames.

To investigate the enhancing effect of borneol on transcorneal permeation of compounds with different hydrophilicities and molecular sizes. Six compounds, namely rhodamine B, sodium-fluorescein, fluorescein isothiocyanate (FITC) dextrans of 4, 10, 20 and 40 kDa were selected as model drugs. Permeation studies were performed using excised cornea of rabbits by a Franz-type diffusion apparatus. The safety of borneol was assessed on the basis of corneal hydration level and Draize eye test. The application of 0.2% borneol to the cornea increased the apparent permeability coefficient by 1.82-(p<0.05), 2.49-(p<0.05), 4.18-(p<0.05), and 1.11-fold (not significant) for rhodamine B, sodium-fluorescein, FITC-dextrans of 4 and 10 kDa, respectively. No significant permeability enhancement of FITC dextrans of 10, 20 and 40 kDa with borneol was found compared to control. The permeability coefficient enhanced by 0.2% borneol was linear correlated to the molecular weight of model drugs (R(2)=0.9976). With the 0.05%, 0.1% and 0.2% borneol application, the corneal hydration values were <83% and Draize scores were <4. Borneol may improve the transcorneal penetration of both hydrophilic and lipophilic compounds without causing toxic reactions, especially hydrophilic ones. Furthermore, 0.2% borneol can enhance the permeation of hydrophilic compounds with molecular weight </= 4 kDa. Hence, borneol can be considered as a safe and effective penetration enhancer for ocular drug administration.

This study was to investigate the synergistic effect of natural borneol/curcumin (NB/Cur) on growth and apoptosis in A375 human melanoma cell line by MTT assay, flow cytometry and Western blotting. Our results demonstrated that NB effectively synergized with Cur to enhance its antiproliferative activity on A375 human melanoma cells by induction of apoptosis, as evidenced by an increase in sub-G1 cell population, DNA fragmentation, PARP cleavage, and caspase activation. Further mechanistic studies by Western blotting showed that after treatment of the cells with NB/Cur, up-regulation of the expression level of phosphorylated JNK and down-regulation of the expression level of phosphorylated ERK and Akt contributed to A375 cells apoptosis. Moreover, NB also potentiated Cur to trigger intracellular ROS overproduction and the DNA damage with up-regulation of the expression level of phosphorylated ATM, phosphorylated Brca1 and phosphorylated p53. The results indicate the combinational application potential of NB and Cur in treatments of cancers.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 76(SRC), determined from a structure estimation method(2), indicates that borneol is expected to have high mobility in soil(SRC). Volatilization of borneol from moist soil surfaces may be expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.38X10-5 atm-cu m/mole(3) based upon its vapor pressure, 5.02X10-2 mm Hg(4), and water solubility, 738 mg/L(5). Borneol is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 5.02X10-2 mm Hg at 25 °C(4). Utilizing the Japanese MITI test, 97% of the Theoretical BOD was reached in 4 weeks indicating that biodegradation is an important environmental fate process in soil(6).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 76(SRC), determined from a structure estimation method(2), indicates that borneol is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces may be expected(3) based upon an estimated Henry's Law constant of 1.38X10-5 atm-cu m/mole(4) derived from its vapor pressure, 5.02X10-2 mm Hg(5), and water solubility, 738 mg/L(6). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 2.2 days and 29 days, respectively(SRC). According to a classification scheme(7), an estimated BCF of 30(SRC), from its log Kow of 2.69(8) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Utilizing the Japanese MITI test, 97% of the Theoretical BOD was reached in 4 weeks indicating that biodegradation is an important environmental fate process in water(9).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), borneol, which has a vapor pressure of 5.02X10-2 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase borneol 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(SRC), calculated from its rate constant of 1.14X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Borneol 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).

Borneol has been identified as a constituent in the volatile extract from fresh rhizomes of ginger and ginger essential oil (Zingiber officinale Roscoe)(1,2). Borneol has been identified as a flavor constituent of Pine Sprout Tea from Korean red pine trees (Pinus densiflora Seib. Et Zucc.)(3).

IDENTIFICATION AND USE: Borneol is a solid. It is used as a flavoring, and as a medication, including traditional Chinese medicine. HUMAN EXPOSURE AND TOXICITY: Borneol does not present a concern for skin sensitization. Toxicity is essentially indistinguishable from that of camphor. Human peripheral blood lymphocytes were exposed to varying concentrations of l-borneol in DMSO up to 600 ug/mL for 4 hr, with and without metabolic activation and 24 hr without metabolic activation. Under the conditions of the study, l-borneol was considered non-clastogenic. ANIMAL STUDIES: As with camphor, laboratory animals appear to be much less susceptible to borneol toxicity than man. Borneol increased the activity of CYP2D in rats orally treated by borneol for 7 days. Borneol has been evaluated for antinociceptive and anti-inflammatory activities in mice. Borneol produced a significant reduction of the nociceptive behavior at the early and late phases of paw licking and reduced the writhing reflex in mice. When the hot plate test was conducted, borneol (in higher dose) produced an inhibition of the nociceptive behavior. Additionally, borneol-treated mice had reduced the carrageenan-induced leukocytes migration to the peritoneal cavity. The mutagenic potential of borneol was assessed in an Ames test with Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98 and TA100 treated with borneol at concentrations up to 5000 ug/ plate in the presence and absence of metabolic activation. Other studies confirming a lack of mutagenic potential in S. typhimurium strains TA98 and TA100 have been published. Under the conditions of the study, borneol is considered not mutagenic in bacteria.

Borneol was identified in the extract of edible Korean Chamchwi plant (Aster scaber Thunb)(1).

Borneol has been reported to occur in over 260 plants. The top 10 with the highest concentrations are as follows(1):[Table#2521]

L-Borneol has been reported to occur in 6 plants(1): /L-Borneol/[Table#2522]

D-Borneol has been reported to occur in 7 plants(1): /D-Borneol/[Table#2523]

Borneol has been detected in the final effluent from one plant in each of the following industries: paint and ink, inorganic chemicals, textile mills, rubber processing, electronics, and mechanical products, and in the final effluent from two plants in the pulp and paper industry(1). Borneol was identified in one sample taken downstream of a publicly owned treatment works in Sauget Il. in June 1980(2). Borneol was identified in 1 out of 2 secondary effluent samples from Fort Polk, LA, in November 1980, at a concentration of 0.054 ug/L(3). Borneol was detected in raw sewage samples collected in May 2007 from a municipal treatment plant in China(4).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of borneol can be estimated to be 76(SRC). According to a classification scheme(2), this estimated Koc value suggests that borneol is expected to have high mobility in soil.

Borneol occurs in citrus peel oils (orange, lemon, lime), cinnamon leaf, cassia leaf, ginger, coriander seed, laurel, Ocimumbasillum, Thymus vulgaris, and Curcuma aeruginosa Roxb(1). Borneol is a component in various plants, plant tissues, and many plant essential oils(2,3).

Both D- and L- isomeric forms of borneol are naturally occurring(1). The most frequently encountered is L-borneol, characteristic of Compositae, Graminaceae and almost all Pinaceae, as well as in Blumea balsamifera. D-Borneal is characteristic of Cupressaceae, Zingiberaceae, lavenderm lavadin and spike oils, as well as oil from Dryobalanops aromatica Gaertn., Dipterocarpaceae(1,2).

/HUMAN EXPOSURE STUDIES/ Based on the available data for the read across material (l-borneol, CAS # 464-45-9) and application of the non-reactive DST, borneol does not present a concern for skin sensitization. The chemical structure of these materials indicates that they would not be expected to react directly with skin proteins. In the human maximization test, two reactions were observed in a panel of 25 subjects to l-borneol; however these were considered questionable due to the presence of concurrent test materials for which numerous strong reactions were observed. The human maximization test was repeated, utilizing the same concentration; no reactions (0/25) indicative of sensitization were observed to l-borneol. In another human maximization test, no reactions indicative of sensitization were observed with 8% l-borneol in petrolatum. /l-Borneol/

/GENOTOXICITY/ There are no data assessing the clastogenicity of borneol. Read across material l-borneol (CAS # 464-45-9), was assessed for clastogenic potential 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 ug/mL for 4 hr, with and without metabolic activation and 24 hr without metabolic activation. Under the conditions of the study, l-borneol was considered non-clastogenic./l-Borneol/

/ALTERNATIVE and IN VITRO TESTS/ The beta-amyloid (Abeta) peptide aggregation with accompanying oxidative stress plays the major role in the pathogenesis of Alzheimer's disease (AD). Some natural compounds, including borneol, shed promising light on AD treatment. The present study was designed to investigate the antioxidative, antiapoptotic effects, and neuroprotection of borneol in human neuroblastoma cells (SH-SY5Y). Oxidative stress was induced by administering 50 uM Abeta into SH-SY5Y cells. Neuroprotective effect of commercially available borneol was examined by determining cell viability with the MTT assay. Intracellular reactive oxygen species (ROS) generation was measured using a fluorometer with further examination of heme oxygenase-1 (HO-1) and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) expression. Apoptosis was examined by measuring the ratio of B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax). Our data indicated that Abeta-induced cell cytotoxicity was inhibited by 100 uM of (-) and (+) borneol treatment. Treatment of borneol significantly decreased ROS generation (p<0.01). The expression of HO-1 and nuclear translocation of Nrf2 were increased by Abeta treatment. This nuclear translocation of Nrf2 was further increased by administration of borneol. Compared with the Abeta treated group, the (+) borneol treated group significantly increased Bcl-2 expression with decreased expression of Bax. Borneol protected SH-SY5Y cells against Abeta-induced toxicity, exerted an antioxidative effect and suppressed apoptosis. It increases our knowledge about neuroprotective mechanism of borneol, and it is hopeful to be a candidate compound for developing therapeutic drug for the prevention and treatment of AD and other Abeta-related neurodegenerative diseases.

/ALTERNATIVE and IN VITRO TESTS/ Curcumin (Cur), an active ingredient from the rhizome of the plant Curcuma longa, has wide anticancer activities. However, due to its poor solubility and hence poor absorption, Cur has limited clinical applications. It is therefore important to develop an effective method to improve its absorption. Natural borneol (NB), a terpene and bicyclic organic compound, has been extensively used as a food additive, and our previous studies show that it can improve the uptake of Cur in cancer cells. However, the anticancer mechanism of NB/Cur remains unclear. In this study, the effects of NB/Cur on HepG2 cells were investigated by proteomic analysis. The results showed that 32 differentially expressed proteins identified by matrix assisted laser desorption ionization time-of-flight mass spectrometry were significantly changed after NB/Cur treated HepG2 cells for 24 h. Moreover, 17 proteins increased and 12 proteins decreased significantly. Biological progress categorization demonstrated that the identified proteins were mainly associated with cell cycle and apoptosis (28.1%). Subcellular location categorization exhibited that the identified proteins were mainly located in nucleus (28.1%) and mitochondrion (21.9%). Among of all proteins, we selected three differential proteins (hnRNPC1/C2, NPM, and PSMA5), which were associated with the p53 pathway. Down-regulation of hnRNPC1/C2 and NPM contributed to the enhancement of phosphorylated p53. Activated p53 and down-regulation of PSMA5 resulted in an increase in p21 protein. Further studies showed that NB/Cur induced reactive oxygen species (ROS) generation, indicating that ROS might be upstream of the G2/M arrest signaling pathway. In summary, the results exhibited the whole proteomic response of HepG2 cells to NB/Cur, which might lead to a better understanding of its underlying anticancer mechanisms.

/OTHER TOXICITY INFORMATION/ / Toxicity is essentially indistinguishable from that of camphor.

Borneol's production and use as a food flavoring, in fragrances, and in the manufacture of its esters(1) may result in its release to the environment through various waste streams(SRC). Borneol has been identified in tobacco smoke and tobacco substitute smoke and in tobacco collected from cigarettes(2).

Chemical: Bicyclo[2.2.1]heptan-2-ol, 1,7,7-trimethyl-, endo-

Regulation (EC) No 1831/2003 (amended)

Bicyclo[2.2.1]heptan-2-ol, 1,7,7-trimethyl-, (1R,2S,4R)-rel- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Bicyclo[2.2.1]heptan-2-ol, 1,7,7-trimethyl-, (1R,2S,4R)-rel- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 13-07-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/24601

Bicyclo[2.2.1]heptan-2-ol, 1,7,7-trimethyl-, (1R,2S,4R)-rel-: Does not have an individual approval but may be used under an appropriate group standard

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

Borneol 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.

To develop a GC-FID method to determine borneol's concentration in mouse tissues, and to investigate the tissue distribution after intravenous and intranasal administrations of borneol, mouse brains, hearts, livers, spleens, lungs and kidneys were collected at 1, 3, 5, 10, 20, 30, 60, 90, 120 min after administration of borneol with the dose of 30.0 mg/kg. The drug in tissues was extracted with ethyl acetate, and borneol's concentration detected by GC, with octadecane as the internal standard. The calibration curve showed a good linear relationship. Extraction recoveries, inter-day and intra-day precisions and stability were in conformity with the analytical requirements of biological samples. Borneol was mainly distributed in most tissues, more in heart, brain and kidney, and less in liver, spleen and lung. The established GC-FID method is applicable for content determination of borneol in tissues. After intravenous and intranasal administrations in mice, borneol is mainly distributed in abundant blood-supply tissues. After intranasal administration, brain tissues showed the highest target coefficient and target effectiveness.

... In order to understand the blood and brain pharmacokinetics after intravenous, intranasal, or oral administration and to investigate the superiority and feasibility of intranasal administration, a simple gas chromatographic (GC) method with flame ionization detection (FID) was developed for the quantification of borneol. Blood samples and brain were collected from mice at 1, 3, 5, 10, 20, 30, 60, 90, and 120 min after intravenous, intranasal, or oral administration of borneol at a dosage of 30.0 mg/kg. Sample preparations were carried out by liquid-liquid extraction with an internal standard solution of octadecane. The pharmacokinetic parameters were calculated /using computer software/. The calibration curves were linear in the range of 0.11-84.24 ug/mL and 0.16-63.18 ug/g for borneol in plasma and brain, respectively. The methodological and extraction recoveries were both in the range of 85%-115%. The intra-day and inter-day variabilities for plasma and brain samples were </= 5.00% relative standard deviation (RSD). The absolute bioavailabilities F of intranasal and oral administrations were 90.68% and 42.99%. The relative brain targeted coefficients Re of intranasal and oral administrations were 68.37% and 38.40%. The GC-FID method developed could be applied to determination and pharmacokinetic study. The borneol from injection was distributed and metabolized fast without absorption process. The borneol from oral administration was distributed more slowly and had the lowest absolute bioavailability. Nasal administration of borneol was quickly absorbed into the blood and brain, was easy to use and had a greater safety than infection, which makes it worthy of further development as an administration route for encephalopathy treatment.

The aim of this work was to study the in situ and in vivo nasal absorption of borneol. A novel single pass in situ nasal perfusion technique was applied to examine the rate and extent of nasal absorption of borneol by rats. Experimental conditions, such as perfusion rate, pH and drug concentration, were investigated. The in situ experiments showed that the nasal absorption of borneol was not dependent on drug concentration, and fitted a first order process. The absorption rate constant, Ka, influenced with an increase in perfusion speed. The borneol was well absorbed in the conditions of the nasal cavity within the pH range and pH value of physiological conditions. In vivo studies of borneol absorption were carried out in rats and the pharmacokinetics parameters of intranasal (in) was compared with intravenous (iv) administration. The bioavailabilities of borneol was 90.82% for i.n. while Tmax values were 10 min. MRT (Mean Residence Time) were 262.55 +/- 67.35 min and 204.22 +/- 14.50 min for in and iv methods, respectively. The results demonstrate that borneol could be absorbed promptly and thoroughly by in administration in rats.

Previous studies have indicated that borneol has double side effects on the central nervous system (CNS), but the mechanism is unknown. The aim of this study was to clarify the relationship between excitation ratio [contents of excitatory amino acids (AAs) versus that of inhibitory] and the content of natural borneol after a single oral dose. Mice were administered a 1.2 g/kg dose of natural borneol (containing 98% D: -borneol) by oral ingestion. Brain samples were collected before administration and at 0.083, 0.167, 0.25, 0.333, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, and 5 hr after administration. The brain concentration of natural borneol and contents of AA neurotransmitters in mice brain were determined by GC-MS and HPLC-FLU, respectively. After per oral application, natural borneol was absorbed rapidly into the brain and could be determined 5 min after dosing. The maximal brain concentration (86.52 ug/g) was reached after 1 hr post-dosing. Natural borneol could affect the contents of AA neurotransmitters in mice brain: L: -aspartic acid increased significantly from 0.083 to 1 hr after administration, L: -glutamic acid increased significantly at 0.333 hr and decreased from 1.5 to 5 hr, gamma-amino-N-butyric acid increased significantly from 0.167 to 5 hr, whereas glycine was not affected. The excitation ratio is the contents of excitatory AAs versus that of inhibitory AAs, which reflects the excitatory or inhibitory state of the body. The excitation ratio elevated transitorily and then declined 0.5 hr post-dosing; there were significant differences between 1.5-5 hr post-dose compared with pre-dose. The present study indicated that natural borneol could affect the contents of AA neurotransmitters, and the change in excitatory ratio led to borneol's double side effects on the CNS.

Used in the manufacture of its esters. in perfumery and incense, and as a food flavoring agent; [HSDB]

In flavors and fragrances; in the manufacture of its esters.

Borneol is used in the reconstitution of the essential oils in which it occurs naturally.

Used in perfumes for soaps and detergents for woody, camphor, and pine notes.

Traditional medicine

For more Uses (Complete) data for BORNEOL (6 total), please visit the HSDB record page.

Racemic borneol is prepared synthetically by reduction of camphor or from pinene.

Although borneol is not an herb per se, it is nevertheless a common ingredient in many traditional Chinese herbal formulas. Borneol is actually a compound derived from dryobalanops aromitaca, a tree that belongs to the teak family. The compound is formed by tapping the trunk of the tree, then cooling the substance and allowing it to harden into a clear crystalline substance. Although some borneol is still made by tapping trees, the vast majority of it is created synthetically from turpentine oil or camphor. The compound is ground down into a fine powder before it can be used medicinally.

PAIN FREE - menthol, methyl salycilate, borneol ointment; Menthol 2%, Methyl Salicylate 1%, Borneol 2%

Grades: technical.

Commercial borneol is often levorotatory ... and contains (-)-borneol and up to 40% isoborneol.

MA YING LONG HEMORRHOIDAL- moschus artifactus, bovis calculus artifactus, margarita, borneolum syntheticum, succinum, calamina (calcined), borax ointment; Moschus - Bovis Calculus - Margarita (Hyriopsis Cuming II) Borneolum syntheticum - Calamina (Calcined) Borax - Succinum

For more Formulations/Preparations (Complete) data for BORNEOL (6 total), please visit the HSDB record page.

Fragrance Ingredients

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavoring Agents -> JECFA Flavorings Index

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Cosmetics -> Undefined function

All Other Chemical Product and Preparation Manufacturing

Bicyclo[2.2.1]heptan-2-ol, 1,7,7-trimethyl-, (1R,2S,4R)-rel-: ACTIVE

The major product in perfumery, by far, is isobornyl acetate; borneol being used at about one-tenth the volume of the former. The most important use for isoborneol is as an intermediate for camphor.