Chinuclidin-3-ol

Cream colored crystalline powder

Crystals form in ethanol

Crystals form in benzene

Danger

H314 (94.2%): Causes severe skin burns and eye damage [Danger Skin corrosion/irritation]

P260, P264, P280, P301+P330+P331, P302+P361+P354, P304+P340, P305+P354+P338, P316, P321, P363, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 52 reports by companies from 6 notifications to the ECHA C&L Inventory.

Wear self-contained breathing apparatus and protective clothing to prevent contact with skin and eyes.

EXTINGUISHING MEDIA Suitable: Water spray. Carbon dioxide, dry chemical powder, or appropriate foam.

Procedure to be followed in case of leak or spill: Evacuate area. Personal precautions: Wear self-contained breathing apparatus, rubber boots, and heavy rubber gloves. Methods for cleaning up: Sweep up, place in a bag and hold for waste disposal. Ventilate area and wash spill site after material pickup is complete.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. 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 soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Observe all federal, state, and local environmental regulations.

In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. Wear suitable protective clothing, gloves, and eye/face protection. In case of accident or if you feel unwell, seek medical advice immediately (show the label where possible).

Wash contaminated clothing before reuse. Discard contaminated shoes. Wash thoroughly after handling.

Do not breathe dust. Do not get in eyes, on skin, on clothing. Avoid prolonged or repeated exposure.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants.

Engineering Controls. Safety shower and eye bath. Use only in a chemical fume hood.

Personal Protective Equipment. Respiratory: Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). 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. Hand: Compatible chemical-resistant gloves. Eye: Chemical safety goggles.

/The Chemical Weapons Convention (CWC) is an international treaty which bans the development, production, stockpiling, and transfer or use of chemical weapons. The Convention mandates the destruction and prohibition of chemical weapons and related facilities and provides for restrictions on international trade in toxic chemicals and precursors./ The Convention's monitoring and verification measures involve submission of declarations regarding ... /Schedule 1, 2, and 3 chemicals/ and inspections by the Organization for the Prohibition of Chemical Weapons of the facilities where these chemicals are produced. ... Schedule 2 lists toxic chemicals and precursors deemed to pose a significant risk to the object and purpose of the CWC because of their lethal or incapacitating properties. Precursors may be used in the final stage for formation, or may be important for the production, of any of the chemicals listed in Schedule 1 or toxic chemicals listed in Schedule 2. Schedule 2 chemicals are not produced in large quantities for commercial ... purposes ... but may be used to manufacture such things as insecticides, herbicides, lubricants or pharmaceutical products (2). Quinuclidin-3-ol is listed in the CWC Annex on Chemicals under Schedule 2 (1).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 8(SRC), determined from a structure estimation method(2), indicates that 3-quinuclidinol is expected to have very high mobility in soil(SRC). Volatilization of 3-quinuclidinol from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 8.1X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(3). 3-Quinuclidinol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.3X10-4 mm Hg(SRC), determined from a fragment constant method(4). Biodegradation data for 3-quinuclidinol were not available(SRC, 2009).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 8(SRC), determined from a structure estimation method(2), indicates that 3-quinuclidinol is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 8.1X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3.2(SRC), from an estimated log Kow of 0.17(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data for 3-quinuclidinol were not available(SRC, 2009).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 3-quinuclidinol , which has an estimated vapor pressure of 3.3X10-4 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 3-quinuclidinol 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 2.3 hours(SRC), calculated from its rate constant of 5.5X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). 3-quinuclidinol does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not susceptible to direct photolysis by sunlight(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 3-quinuclidinol can be estimated to be 8(SRC). According to a classification scheme(2), this estimated Koc value suggests that 3-quinuclidinol is expected to have very high mobility in soil.

/SIGNS AND SYMPTOMS/ Skin Contact: Causes burns. Skin Absorption: May be harmful if absorbed through the skin. Eye Contact: Causes burns. Inhalation: May be harmful if inhaled. Material is extremely destructive to the tissue of the mucous membranes and upper respiratory tract. Ingestion: May be harmful if swallowed.

/SIGNS AND SYMPTOMS/ Inhalation may result in spasm, inflammation and edema of the larynx and bronchi, chemical pneumonitis, and pulmonary edema. Symptoms of exposure may include burning sensation, coughing, wheezing, laryngitis, shortness of breath, headache, nausea, and vomiting. Material is extremely destructive to tissue of the mucous membranes and upper respiratory tract, eyes, and skin.

/OTHER TOXICITY INFORMATION/ Corrosive.

3-Quinuclidinol's production and use as a precursor in the synthesis of chemical warfare agent 3-quinuclidinyl benzilate (BZ)(1) in the manufacture of pharmaceuticals(1), synthesis of anticholinergic drug clidinium bromide(2), and synthesis of antihypotensive drug aceclidine(2) may result in its release to the environment through various waste streams(SRC).

An estimated BCF of 3.2 was calculated for 3-quinuclidinol(SRC), using an estimated log Kow of 0.17(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for 3-quinuclidinol is estimated as 8.1X10-10 atm-cu m/mole at 25 °C(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 3-quinuclidinol is expected to be essentially nonvolatile from water surfaces(2). The Henry's Law constant of 3-quinuclidinol indicates that volatilization from moist soil surfaces will not occur(SRC). 3-Quinuclidinol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.3X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(3).

/ALTERNATIVE and IN VITRO TESTS/ The preparation of R-(-)-3-quinuclidinol and its acetate ester is reported. These compounds, together with their racemates, were tested as inhibitors and substrates of the enzyme acetylcholinesterase. The results suggest that the enzyme active site is stereospecific toward R-(-)-3-quinuclidinol hydrochloride when acting as an inhibitor. Both (+/-)- and R-(-)-3-acetoxyquinuclidine hydrochloride are substrates of the enzyme, but the S-enantiomer probably has some affinity for the enzyme also.

/ALTERNATIVE and IN VITRO TESTS/ Choline uptake into cholinergic neurons for acetylcholine (ACh) synthesis is by a specific, high-affinity, sodium- and temperature-dependent transport mechanism (HAChU). To assess the role of choline availability in regulation of ACh synthesis, the structure-activity relationships of several ... quinuclidinyl analogs were evaluated in a dose response manner. ... The most potent quinuclidinyl derivative was the N-methyl-3-quinuclidinone (I50 = 5.6 X 10-7 M). This compound had approximately 100-fold greater inhibitory activity than the corresponding racemic alcohol, suggesting that the 3-hydroxyl functional group is not absolutely essential for activity. Increasing the size of the N-functional group from a methyl to an allyl in the alcohol led to a 10-fold increase in activity. However, removal of the quaternizing N-methyl group yielding the tertiary amine, 3-quinuclidinol hydrochloride, greatly reduced its capacity to inhibit HAChU. Of the 2-benzylidene-3-quinuclidinone derivatives studied, only the m-chloro derivative significantly reduced HAChU. /3-Quinuclidinol hydrochloride/

The rate constant for the vapor-phase reaction of 3-quinuclidinol with photochemically-produced hydroxyl radicals has been estimated as 5.5X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 2.3 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). 3-Quinuclidinol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). 3-Quinuclidinol does not contain chromophores that absorb at wavelengths >290 nm(3) and therefore is not susceptible to direct photolysis by sunlight(SRC).

3-Quinuclidinol's production and use as a synthetic precursor to chemical warfare agents and drugs may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 3.3X10-4 mm Hg at 25 °C indicates 3-quinuclidinol will exist solely as a vapor in the atmosphere. Vapor-phase 3-quinuclidinol will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 2.3 hours. 3-Quinuclidinol does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight. If released to soil, 3-quinuclidinol is expected to have very high mobility based upon an estimated Koc of 8. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 8.1X10-10 atm-cu m/mole. 3-Quinuclidinol is not expected to volatilize from dry soil surfaces based upon its vapor pressure. If released into water, 3-quinuclidinol is not expected to adsorb to suspended solids and sediment based upon the Koc. Volatilization from water surfaces is not expected to be an important fate process based upon Henry's Law constant of 3-quinuclidinol. An estimated BCF of 3.2 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since 3-quinuclidinol lacks functional groups that hydrolyze under environmental conditions. Occupational exposure to 3-quinuclidinol may occur through inhalation of dust and dermal contact at workplaces where it is produced or used. (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 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. /Incapacitating Agents/

/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 it necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . Demonstrate a friendly attitude and use firm restraint when necessary. All dangerous objects must be removed from the area and anything likely to be swallowed should be kept away from patients, because bizarre delusions may occur. For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Use rapid cooling techniques to manage hyperthermia ... . 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 ... . /Incapacitating Agents/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag-valve-mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Treat seizures or sedate LSD patients with diazepam (Valium) or lorazepam (Ativan) ... . Administer physostigmine for symptomatic BZ or Agent 15 exposure only .... . Use proparacaine hydrochloride to assist eye irrigation ... . /Incapacitating Agents/

Precursor in the synthesis of chemical warfare agent 3-quinuclidinyl benzilate (BZ)

Used in the manufacture of pharmaceuticals

Benzilate (ester) has been used as an incapacitating agent in chemical warfare.

THERAP CAT: Hypotensive; acetate (ester) as cholinergic

... Precursor to BZ and Arsenic trichloride.

Synthesis: 3-Quinuclidinone hydrochloride and hydrogen

Sternbach, US 2648667 (1953 to Hoffmann-La Roche)

1-Azabicyclo[2.2.2]octan-3-ol: ACTIVE

Used in the synthesis of anticholinergic drug clidinium bromide /Clidinium bromide/

Used in the synthesis of antihypotensive drug aceclidine /Aceclidine/