Phenylacetone

DEA Schedule II Controlled Substance -> Immediate precursors

Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds

Pharmaceuticals -> Metabolite of Lisdexamfetamine

This chemical does not meet GHS hazard criteria for 94.1% (48 of 51) of all reports.

Not Classified

Aggregated GHS information provided per 51 reports by companies from 4 notifications to the ECHA C&L Inventory.

Warning

H227: Combustible liquid [Warning Flammable liquids]

P210, P280, P370+P378, P403, and P501 (click each P-code to see the statement)

Chemical: 2-Propanone, 1-phenyl-

DEA schedule II controlled substance

Commission Regulation (EC) No 1565/2000 (Repealed by Com. Implementing Reg. (EU) No 872/2012)

Status: Active Update: 03-05-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/23506

2-Propanone, 1-phenyl-: Does not have an individual approval but may be used under an appropriate group standard

Schedule II shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Immediate precursors. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances: (1) Immediate precursor to amphetamine and methamphetamine. Phenylacetone (DEA Code Number: 8501) is included on this list.

Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Wear self-contained breathing apparatus for firefighting if necessary. Use water spray to cool unopened containers.

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

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: This combustible material may be burned in a chemical incinerator equipped with an afterburner and scrubber. Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging: Dispose of as unused product.

ACCIDENTAL RELEASE MEASURES Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. Beware of vapors accumulating to form explosive concentrations. Vapors can accumulate in low areas. Prevent further leakage or spillage if safe to do so. Do not let product enter drains.

Avoid contact with skin and eyes. Avoid inhalation of vapor or mist. Keep away from sources of ignition - No smoking. Take measures to prevent the build up of electrostatic charge.

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

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.

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).

Skin protection: Handle with gloves.

Body Protection: Impervious 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 respirator with multipurpose combination (US) or type ABEK (EN 14387) 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).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a log Kow of 1.44(2) and a regression-derived equation(3), indicates that phenyl 2-propanone is expected to have high mobility in soil(SRC). Volatilization of phenyl 2-propanone from moist soil surfaces may be an important fate process(SRC) given an estimated Henry's Law constant of 4.0X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Phenyl 2-propanone has an estimated vapor pressure of 0.16 mm Hg(SRC), determined from a fragment constant method(3) and exists as a liquid under environmental conditions; therefore, phenyl 2-propanone may volatilize from dry soil. When exposed to soil microorganisms, phenyl 2-propanone was rapidly metabolized(5), suggesting that biodegradation may be an important enviornmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a log Kow of 1.44(2) and a regression-derived equation(3), indicates that phenyl 2-propanone is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(4) based upon an estimated Henry's Law constant of 4.0X10-6 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 and 80 days, respectively(SRC). According to a classification scheme(5), an estimated BCF of 4.1(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). When exposed to soil microorganisms, phenyl 2-propanone was rapidly metabolized(6), suggesting that biodegradation may be an important enviornmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), phenyl 2-propanone, which has an estimated vapor pressure of 0.16 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 phenyl 2-propanone 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 5.7(SRC), calculated from its rate constant of 5.6X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Phenyl 2-propanone contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: Phenyl 2-propanone is immediate precursor to amphetamine and methamphetamine, and a DEA Schedule II substance. HUMAN STUDIES: The quality and quantity of illicit methamphetamine has recently increased due to introduction of a new precursor, phenyl 2-propanone. ANIMAL STUDIES: Various ring-methoxylated 1-phenyl-2-propanols and 1-phenyl-2-propanones were synthesized and pharmacologically evaluated. Most compounds had depressant-like activity. The ketones were readily reduced by rabbit liver microsomes.

The Koc of phenyl 2-propanone is estimated as 80(SRC), using a log Kow of 1.44(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that phenyl 2-propanone is expected to have high mobility in soil.

Phenyl 2-propanone's production and use as an intermediate for the synthesis of pharmaceuticals(1) may result in its release to the environment through various waste streams(SRC). Phenyl 2-propanone is on the US DEA (Drug Enforcement Administration) list of schedule II controlled substances, as an immediate precursor to amphetamine and methamphetamine(2). Phenyl 2-propanone is a constituent of tobacco, tobacco smoke, and tobacco substitute smoke(3).

AEROBIC: Chemicals associated with clandestine drug laboratories are often disposed of covertly into soil, sewerage systems, or public waste management facilities. There are two significant issues relating to such dumps of materials; they might contain valuable evidence as to drug manufacture, and they might be a source of pollution. This study presents initial findings in relation to the impact microorganisms from environmental sources have upon drugs, their precursors, and manufacturing by-products. The aim of this study was to identify which chemicals associated with clandestine drug laboratories persist in the environment in order to allow forensic drug chemists to link discarded residues with the method of manufacture, and to allow the environmental impact of clandestine drug laboratories to be assessed accurately. When exposed to soil microorganisms, phenyl-2-propanone (P2P) was rapidly metabolized into mixtures of 1-phenyl-2-propanol, 1-phenyl-1,2-propanedione, 1-hydroxy-1-phenyl-2-propanone, 2-hydroxy-1-phenyl-1-propanone, and the two diastereoisomers of 1-phenyl-1,2-propanediol. On the other hand, when exposed under the same conditions, methylamphetamine sulfate (MAS) remained virtually unchanged. Implications relating to evidence gathering for forensic purposes and to environmental assessment of clandestine drug laboratories are discussed.

An estimated BCF of 4.1 was calculated in fish for phenyl 2-propanone(SRC), using a log Kow of 1.44(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 phenyl 2-propanone is estimated as 4.0X10-6 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that phenyl 2-propanone 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 80 days(SRC). Phenyl 2-propanone's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). Phenyl 2-propanone has an estimated vapor pressure of 0.16 mm Hg(SRC), determined from a fragment constant method(3) and exists as a liquid under environmental conditions; therefore, phenyl 2-propanone may volatilize from dry soil.

/OTHER TOXICITY INFORMATION/ Various ring-methoxylated 1-phenyl-2-propanols and 1-phenyl-2-propanones were synthesized and pharmacologically evaluated. Most compounds had depressant-like activity. The ketones were readily reduced by rabbit liver microsomes. No reductase activity was found in rat and mouse liver preparations. Partition coefficients were determined, and a linear correlation between LRA50's (loss of righting ability in 50% of the mice) and partition coefficients was observed for six of the compounds investigated.

The rate constant for the vapor-phase reaction of phenyl 2-propanone with photochemically-produced hydroxyl radicals has been estimated as 5.6X10-12 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 5.7 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Phenyl 2-propanone is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). Phenyl 2-propanone contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Occupational exposure to phenyl 2-propanone may occur through inhalation and dermal contact with this compound at workplaces where phenyl 2-propanone is produced or used. Limited monitoring and use data indicate that the general population may be exposed to phenyl 2-propanone via ingestion of food, inhalation of tobacco smoke, and inhalation and dermal contact with consumer products containing phenyl 2-propanone. (SRC)

Schedule II shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. ... Immediate precursors. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances: (1) Immediate precursor to amphetamine and methamphetamine. Phenylacetone (DEA Code Number: 8501) is included on this list.

Marked differences were observed, in the ability of fortified 9000 g liver homogenate supernatants from three species to reduce 1-phenyl-2-propanone to the corresponding alcohol. This metabolic keto-reduction was negligible in homogenates from the rat and extensive in the rabbit; guinea-pig liver homogenates had intermediate ability. Metabolic oxidation of 1-phenyl-2-propanol was negligible in all three species. The amount of deamination of amphetamine and of N-n-propylamphetamine was approximately equal, in vitro, in rats and guinea-pigs but two to three times greater in liver homogenates from rabbits. Approximately three times more deaminated products were formed from the in vitro metabolism of N-n-propylamphetamine than from amphetamine metabolism by all three species.

Phenylacetone was found to be the major metabolite formed when 2-nitro-1-phenylpropane was incubated with rabbit liver microsomes. The enzymatic character of the reaction was demonstrated by the increase of product with microsomal protein and dependency on NADPH and oxygen. Furthermore, phenobarbital induction markedly increased the formation of phenylacetone. Carbon monoxide decreased the reaction indicating the involvement of a metalloenzyme. Experiments with H2(18)O indicated that the carbonyl oxygen originated from water. It is suggested that the microsomal metabolism of 2-nitro-1-phenylpropane involves an enzymatic step followed by chemical hydrolysis of an intermediate, possibly a secondary nitronic acid.

Amphetamine is deaminated oxidatively by highly purified rat liver mitochondria. This monoamineoxidase (MAO) is an enzyme of the mitochondrial outer membrane and its activity is about two times higher than that of the microsomal MAO. Anaerobic incubations with mitochondria reduce phenylacetone, an important metabolite of amphetamine, to phenylisopropanol. The ketoreductase is localized in the mitochondrial inner membrane or its matrix.

Fenetylline is metabolized in humans on two pathways. In addition to previously described degradation to amphetamine and 7-oxyethyltheophylline fenetylline undergoes moreover oxydative N-dealkylation to yield 7-aminoethyltheophylline and phenylacetone.

Used in organic synthesis and to make benzyl radicals by photolysis; [Merck Index] A flavoring agent that naturally occurs in passion fruit juice; [EFSA]

Controlled substance (precursor to amphetamine and methamphetamine); [Merck Index]

Phenylacetone (DEA Code Number: 8501) is a Schedule II controlled substance.

Schedule II Controlled Substance: (A) The drug or other substance has a high potential for abuse; (B) The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions; and (C) Abuse of the drug or other substances may lead to severe psychological or physical dependence.

Synthesis of pharmaceuticals.

In organic synthesis; production of benzyl radicals by photolysis.

Phenyl acetone

Benzyl methyl ketone; Methyl benzyl ketone; 2-Propanone, 1-phenyl

IFRA_STD_174.pdf

43

IFRA 51st Amendment - Guidance for the use of IFRA Standards

Prohibition: This material should not be used as a fragrance ingredient

1-Phenyl-2-propanone is produced by catalytic ketonization of phenylacetic acid with acetic acid over an alumina-supported cerium oxide catalyst at 400-500 °C. It may also be produced by the rearrangement of phenylpropylene oxide on zeolites or oxidation of 2-phenylpropanol.

2-Propanone, 1-phenyl-: ACTIVE

Analog of propiophenone where carbonyl group is on the 2 carbon atom instead of the 1 carbon atom of the side chain.