(+)-Nootkatone

218.33

218.33

4676969

225-124-4

IZ2Y119N4J

DTXSID8047050

Crystals from light petroleum; commercial product is a colorless to yellowish liquid

29142990

17.07000

3.84

Solid

1.0±0.1 g/cm3

31-34 °C @ Solvent: Methanol

125°C0,5mm

99°C

1.503

Slightly soluble in ethanol and chloroform. Partly soluble in water.

2-8°C

0.003 mm Hg at 25 °C (est)

>1 (Air = 1)

Optical rotation: +195.5 deg (c = 1.5 in CHCL3)

Grapefruit odor

Grapefruit taste

Henry's Law constant = 1.4X10-4 atm-cu m/mole at 25 °C (est)

Hydroxyl radical reaction rate constant = 1.5X10-10 cu cm/molec-sec at 25 °C (est)|Ozone reaction rate constant = 2.3X10-17 cu cm/molec-sec at 25 °C (est)

NONH for all modes of transport

2

23-24/25

Stable. Incompatible with strong oxidizing agents.

P280

H317

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

Incompatible materials: Strong oxidizing agents.

Nootkatone 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.

Not Classified| |Warning|H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]|P264, P280, P305+P351+P338, and P337+P313|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

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

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

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas.; Environmental precautions: Do not let product enter drains.; Methods and materials for containment and cleaning up: Sweep up and shovel. Keep in suitable, closed containers for disposal.

Precautions for safe handling: Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.|Appropriate engineering controls: General industrial hygiene practice.

IDENTIFICATION AND USE: Nootkatone forms crystals; however, commercial product is a colorless to yellowish liquid. It is used in beverages to impart grapefruit flavor; in fragrance compositions with other citrus oils. Potential bio-based pesticide to kill ants, termites, mosquitoes, cockroaches, and ticks, including Ixodes scapularis (blacklegged tick), whose bite can transmit bacteria that cause Lyme disease in humans and other animals. HUMAN EXPOSURE AND TOXICITY: No human data were found. ANIMAL STUDIES: In a 28-day study, rats (male and female) were given nootkatone at a dose of 10 mg/kg bw per day by oral gavage. No clinically observable signs of toxicity were reported. Histopathological examination revealed accumulation of globular eosinophilic material in the tubular epithelium of male rats treated with nootkatone at a dose of 10 mg/kg bw per day. This finding is consistent with the presence of hyaline droplet nephropathy, which results from the excessive accumulation of alpha-2u-globulin in renal proximal tubular epithelial cells. Accumulation of alpha-2u-globulin in the proximal tubular epithelium is considered to be of no relevance to humans. ECOTOXICITY STUDIES: Encapsulation of nootkatone improved toxicity for tick control, reduced nootkatone volatility, and reduced plant phytotoxicity.

/PLANTS/ Nootkatone is a component of grapefruit oil that is toxic to the disease-vectoring tick, Ixodes scapularis Say, but unfortunately causes phytotoxicity to treated plants and has a short residual activity due to volatility. We prepared a lignin-encapsulated nootkatone formulation to compare with a previously used emulsifiable formulation for volatility, plant phytotoxicity, and toxicity to unfed nymphs of I. scapularis. Volatility of nootkatone was measured directly by trapping nootkatone vapor in a closed system and indirectly by measuring nootkatone residue on treated filter paper after exposure to simulated sunlight (Xenon). After 24 hr in the closed system, traps collected only 15% of the nootkatone applied as the encapsulated formulation compared with 40% applied as the emulsifiable formulation. After a 1-hr light exposure, the encapsulated formulation retained 92% of the nootkatone concentration compared with only 26% retained by the emulsifiable formulation. For plant phytotoxicity, cabbage, Brassica oleracea L., leaves treated with the encapsulated formulation expressed less necrosis, retaining greater leaf weight compared with leaves treated with the emusifiable formulation. The nootkatone in the emulsifiable formulation was absorbed by cabbage and oat, Avena sativa L., plants (41 and 60% recovered 2 hr after application, respectively), as opposed to 100% recovery from the plants treated with encapsulated nootkatone. Using a treated vial technique, encapsulated nootkatone was significantly more toxic to I. scapularis nymphs (LC50 = 20 ng/sq cm) compared with toxicity of the emulsifiable formulation (LC50 = 35 ng/sq cm). Thus, the encapsulation of nootkatone improved toxicity for tick control, reduced nootkatone volatility, and reduced plant phytotoxicity.

Nootkatone is reportedly found in grapefruit oil and juice and in oils of bergamont, lemon, lime, orange and tangerine(1). Nootkatone occurs in Alaska yellow cedar trees and vetiver grass(2).

Nootkatone's production and use as a flavoring ingredient to impart grapefruit flavor in beverages and use in fragrance compositions(1) may result in its release to the environment through various waste streams(SRC). Its potential use as a bio-based pesticide(2) would result in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2210(SRC), determined from a structure estimation method(2), indicates that nootkatone is expected to have slight mobility in soil(SRC). Volatilization of nootkatone from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.4X10-4 atm-cu m/mole(SRC), using a fragment constant estimation method(2). Nootkatone is bicyclic terpene and screening test results of other bicyclic terpenes indicate the compounds are generally biodegradable, but not readily biodegradable(3).|FIELD STUDY: Nootkatone is reported to rapidly turn to vapor when applied in the field as an essential oil for bio-based pesticide applications(3). Field applications of nootkatone did not last more than 3 days before pest control broke down. Tests for residual activity showed that 95% of the nootkatone (when applied as an emulsifiable concentrate) had disappeared by 5 days versus only 45% for a lignin-encapsulated nootakatone mixture, indicating it had substantially slowed the oil's volatility(1).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2210(SRC), determined from a structure estimation method(2), indicates that nootkatone is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 1.4X10-4 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 13.5 hours and 8.6 days, respectively(SRC). According to a classification scheme(4), an estimated BCF of 159(SRC), from its log Kow of 3.84(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is high(SRC). Nootkatone is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Nootkatone is an olefin and olefins in surface waters exposed to sunlight react with photo-oxidants (such as hydroxyl radicals, peroxy radicals and singlet oxygen) with a half-life on the order of 25 days(5). Nootkatone is bicyclic terpene and screening test results of other bicyclic terpenes indicate the compounds are generally biodegradable, but not readily biodegradable(6).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), nootkatone, which has an estimated vapor pressure of 0.003 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 nootkatone 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 2.6 hours(SRC), calculated from its rate constant of 1.5X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Vapor-phase nootkatone is degraded in the atmosphere by reaction with ozone; the half-life for this reaction in air is estimated to be 12 hours(SRC), calculated from its rate constant of 2.3X10-17 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Vapor-phase nootkatone is also degraded in the atmosphere by reaction with nitrate radicals; the half-life for this reaction in air is estimated to be 0.8 hours(SRC), calculated from a rate constant of 1.0X10-12 cu cm/molecule-sec at 24 °C(SRC) for analogous olefins(3). The nitrate radical (NO3) is the dominant atmospheric oxidant during the night-time in most atmospheric environments(4), therefore, night-time degradation appears to be a major fate process for nootkatone(SRC). Nootkatone contains chromophores that absorb at wavelengths >290 nm(5) and, therefore, may be susceptible to direct photolysis by sunlight.

The rate constant for the vapor-phase reaction of nootkatone with photochemically-produced hydroxyl radicals has been estimated as 1.5X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2.6 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of nootkatone with ozone has been estimated as 2.3X10-17 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(1); this corresponds to an atmospheric half-life of about 12 hours at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(2). Based on analogy to measured rate constants for similar olefins(2), the rate constant for the vapor-phase reaction of nootkatone with nitrate radicals is on the order of 1X10-12 cu cm/molecule-sec at 25 °C(SRC); this corresponds to an atmospheric half-life of about 0.8 hours(SRC) at an atmospheric concentration of 2.5X10+8 nitrate radicals per cu cm(3). The nitrate radical (NO3) is the dominant atmospheric oxidant during the night-time in most atmospheric environments(4), therefore, night-time degradation appears to be a major fate process for nootkatone(SRC). Nootkatone is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(5). Nootkatone is an olefin and olefins in surface waters exposed to sunlight react with photo-oxidants (such as hydroxyl radicals, peroxy radicals and singlet oxygen) with a half-life on the order of 25 days(6). Nootkatone contains chromophores that absorb at wavelengths >290 nm(5) and, therefore, may be susceptible to direct photolysis by sunlight.

An estimated BCF of 159 was calculated in fish for nootkatone(SRC), using a log Kow of 3.84(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is high(SRC), provided the compound is not metabolized by the organism(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of nootkatone can be estimated to be 2210(SRC). According to a classification scheme(2), this estimated Koc value suggests that nootkatone is expected to have slight mobility in soil.

The Henry's Law constant for nootkatone is estimated as 1.4X10-4 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that nootkatone 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 13.5 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)(2) is estimated as 8.6 days(SRC). Nootkatone's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). Nootkatone is reported to rapidly turn to vapor when applied in the field as an essential oil for bio-based pesticide applications(3); encapsulating the nootkatone in lignin slows the environmental loss in field application(3). Volatility measurements in a closed system for 24-hours found 40% of the applied nootkatone volatilized from emulsifiable formulations, but only 15% from encapsulated formulations(4).

Nootkatone was detected in Valencia and California navel orange citrus oils at levels of 0.015-0.051 wt%(1). Nootkatone has been identified in grapefruit, oranges and lemons(2); it is an important part of the taste of grapefruit(2). Reported to occur in canned orange juice(3).

Occupational exposure to nootkatone may occur through inhalation and dermal contact with this compound at workplaces where nootkatone is produced or used. Monitoring and use data indicate that the general population may be exposed to nootkatone via inhalation of ambient air, ingestion of food and dermal contact with consumer products containing nootkatone. (SRC)

/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 ... . Cover skin burns with dry sterile dressings after decontamination ... . /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/

nootkatone

2(3H)-Naphthalenone, 4,4a,5,6,7,8-hexahydro-4,4a-dimethyl-6-(1-methylethenyl)-, (4R,4aS,6R)-: ACTIVE

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|Flavoring Agents -> JECFA Flavorings Index

Flavoring Agents