Acetonoxim

log Kow = 0.12

0.12

Density: 0.9113 g/cm cu at 62 °C

Density: 0.9113 g/cm cu at 62 °C

Columnar prisms

Colorless crystals

In water, 30.0 to 32.7% w/w at 20.0 °C

Soluble in water

Soluble in ethanol, diethyl ether, chloroform, ligroin

133 °C

Boiling point = 134.8 °C at 728 mm Hg

Hazardous decomposition products formed under fire conditions. - Carbon oxides, Nitrogen oxides (NOx)

When heated to decomposition it emits toxic fumes of /nitrogen oxides/.

3.12 [mmHg]

1.82 mm Hg at 25 °C (242 hPa)

Danger

H312: Harmful in contact with skin [Warning Acute toxicity, dermal]

P203, P260, P261, P264+P265, P271, P272, P280, P302+P352, P304+P340, P305+P354+P338, P317, P318, P319, P321, P333+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Danger

H228 (99.3%): Flammable solid [Danger Flammable solids]

P203, P210, P240, P241, P261, P264+P265, P272, P280, P302+P352, P305+P354+P338, P317, P318, P321, P333+P317, P362+P364, P370+P378, P405, and P501 (click each P-code to see the statement)

Hazard Traits - Carcinogenicity

Status: Active Update: 17-10-2019 https://echa.europa.eu/registration-dossier/-/registered-dossier/5744

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

Flam. Sol. 2 (99.3%)

Carc. 1B

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.

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.

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. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product

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.

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. 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

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

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. Ensure that the local ventilation moves the contaminant away from the worker.

Eye/face protection: Face shield and safety glasses 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: Complete suit protecting against chemicals. 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).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1.3(SRC), determined from a log Kow of 0.12(2) and a regression-derived equation(3), indicates that acetoxime is expected to have very high mobility in soil(SRC). The pKa of acetoxime is 12.42(4), indicating that this compound will exist as its neutral species in the environment (pH 5-9). Volatilization of acetoxime from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.8X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(3). Acetoxime is expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 1.82 mm Hg at 25 °C(5). A 0% of theoretical BOD using domestic sewage in the Closed Bottle test(6) suggests that biodegradation is not an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1.3(SRC), determined from a log Kow of 0.12(2) and a regression-derived equation(3), indicates that acetoxime 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 7.8X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(3). Using this Henry's Law constant and an estimation method(5), volatilization half-lives for a model river and model lake are 4 days and 33 days, respectively(SRC). According to a classification scheme(6), an estimated BCF of 3.2(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low. A 0% of theoretical BOD using domestic sewage in the Closed Bottle test(7) suggests that biodegradation is not 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), acetoxime, which has a vapor pressure of 1.82 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase acetoxime 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 48 days(SRC), calculated from its rate constant of 3.3X10-13 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Acetoxime 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).

IDENTIFICATION AND USE: Acetoxime is a solid. It is used in organic synthesis (intermediate), as a solvent for cellulose ethers, and as a primer for diesel fuels. HUMAN STUDIES: Acetoxime has been tested in vitro as an experimental medication for herpes infection. ANIMAL STUDIES: Acetoxime was tested for carcinogenicity by chronic administration in the drinking water to male and female rats. The dose of 1.0 g/liter was administered 5 days/week for 18 months (total dose, 6.2 -7.0 g/rat). Acetoxime induced benign hepatocellular adenomas in 80% of the males but did not produce tumors in the females. The 90 day-NOAEL of the test substance in rats by the oral route was 15 mg/kg bw/day in both sexes. No effects were observed in the reproductive organs or tissues up to the highest dose tested (50 mg/kg bw/day). Acetoxime was negative in the Ames test with TA97, TA98, TA100 and TA1535 with and without metabolic activation. Acetoxime was genotoxic in Drosophila melanogaster. When tested in vivo acetoxime was found to induce a specific pattern of base damage in rat liver DNA and RNA, including the induction of increased levels of 8-hydroxyguanine. Because acetoxime was a weaker carcinogen in female rats than male rats, its ability to induce damage in liver and kidney nucleic acids was examined in male and female rats 6 and 18 hr after administration. Significantly lower levels of 8-hydroxydeoxyguanosine, 8-hydroxyguanosine and other presumed modified nucleosides discernible by high-performance liquid chromatography with electrochemical detection were found in liver nucleic acids of female rats.

The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for acetoxime is available.[Available from, as of February 1, 2019: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

The Koc of acetoxime is estimated as 1.3(SRC), using a log Kow of 0.12(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that acetoxime is expected to have very high mobility in soil.

AEROBIC: Acetoxime, present at 2.5 mg/L, reached 0% of its theoretical BOD in 28 days using a domestic sewage inoculum in the OECD 301D Closed Bottle test; therefore, biodegradation is not expected tp be an important environmental fate process(1).

An estimated BCF of 3 was calculated in fish for acetoxime(SRC), using a log Kow of 0.12(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 acetoxime is estimated as 7.8X10-6 atm-cu m/mole(SRC) developed using a fragment constant estimation method(1). This Henry's Law constant indicates that acetoxime 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 4 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 33 days(SRC). Acetoxime is expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 1.82 mm Hg(3)(SRC).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Acetoxime was tested for carcinogenicity by chronic administration in the drinking water to male and female outbred MRC-Wistar rats. The dose of 1.0 g/L was administered 5 days/week for 18 months (total dose, 6.2 -7.0 g/rat). The test compound induced benign hepatocellular adenomas in 80% of the males but did not produce tumors in the females.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Initiation-Promotion/ We tested the ability of phenobarbital and two liver carcinogens, acetoxime and 1-nitroso-5,6-dihydrouracil (NDHU), to induce hyperplastic liver nodules (HLN) in MRC-Wistar and Wistar rats, using a system that included a single diethylnitrosamine (DEN) treatment, partial hepatectomy, and administration of the test compound in drinking water for 8 weeks. All three compounds induced significant HLN frequencies (number of HLN/sq cm) in both rat strains. When the results for each strain were "normalized" for each compound and then combined, HLN frequency in MRC-Wistar rats was significantly lower (P less than 0.01) than that in Wistar rats. The weak liver carcinogen 3-nitroso-2-oxazolidinone (NOZ) did not induce a significant HLN frequency in MRC-Wistar rats. Acetoxime was highly volatile and was not mutagenic in the Ames test under a variety of conditions. The results for acetoxime are of interest because simple oximes are common constituents of oil paints. HLN induction by nitrosodihydrouracil is of interest because, unlike most liver carcinogens, this compound probably does not require metabolic activation and shows only a mild acute hepatoxicity.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ /Rat Crj:CD(SD) male/female/ The 90 day-NOAEL of the test substance in rats by oral route was 15 mg/kg bw/day in both sexes. No effects were observed in the reproductive organs or tissues up to the highest dose tested (50 mg/kg bw/day).

/GENOTOXICITY/ Acetoxime (ACO) and 2-nitropropane (2-NP), both industrially important chemicals and known hepatocarcinogens in rats, induced increased levels of 8-hydroxy-guanine in liver DNA and RNA of male Sprague-Dawley and F344 rats after either oral or i.p. administration. Both compounds also produced qualitatively the same patterns of other apparent modifications of liver DNA and RNA nucleosides, discernible by HPLC with electrochemical detection. Six hours after administration, the effects of 2-NP on liver nucleic acids were more pronounced in F344 rats than in Sprague-Dawley rats, suggesting that 2-NP may prove to be a stronger carcinogen in the F344 strain. The effects of ACO, a weaker carcinogen than 2-NP, were less than those of the nitroalkane in both rat strains. These results suggest that the hepatocarcinogenicity of ACO, like that of 2-NP, may depend on increased generation of reactive oxygen species capable of producing DNA and RNA base damage in rat liver. In addition, the data support the hypothesis that the hepatocarcinogenicity of ACO depends on its partial in vivo N-oxidation to 2-NP.

For more Non-Human Toxicity Excerpts (Complete) data for Acetoxime (7 total), please visit the HSDB record page.

The rate constant for the vapor-phase reaction of acetoxime with photochemically-produced hydroxyl radicals has been estimated as 3.3X10-13 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 48 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Acetoxime is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Acetoxime 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).

Previously, the secondary nitroalkane 2-nitropropane, a strong hepatocarcinogen in rats, had been shown to induce the formation of 8-aminoguanine in both DNA and RNA of rat liver through a sulfotransferase-mediated pathway. This pathway was postulated to convert the carcinogen into an aminating species. To submit this postulate to further test, we examined liver proteins of rats treated with 2-nitropropane, other carcinogenic secondary nitroalkanes, or the related rat liver tumorigen acetoxime for the presence of 3-aminotyrosine, the expected product of tyrosine amination. Using ion-pair and/or cation-exchange high-performance liquid chromatography with electrochemical detection, we found that the liver cytosolic proteins of these animals contained 0.1-1.5 mol of 3-aminotyrosine/10(3) mol of tyrosine. Treatment with the noncarcinogenic primary nitroalkane 1-nitropropane or with other primary nitroalkanes did not produce an analogous increase in the aminated amino acid (level of detection estimated at approximately 0.01 mol/10(3) mol of tyrosine). ... In vitro studies with acetoxime-O-sulfonate and hydroxylamine-O-sulfonate showed that these proposed intermediates in the activation pathway of 2-nitropropane react with guanosine to give 8-aminoguanosine, N1-aminoguanosine, and 8-oxoguanosine and also react with tyrosine to give 3-aminotyrosine and 3-hydroxytyrosine. The in vitro amination and oxidation of guanosine at C8 were also produced by acetophenoxime-O-sulfonate and 2-heptanoxime-O-sulfonate. These results provide additional evidence for the production of a reactive species capable of aminating nucleic acids and proteins from 2-nitropropane and other carcinogenic secondary nitroalkanes by a pathway involving oxime- and hydroxylamine-O-sulfonates as intermediates.

Acetoxime and methylethyl ketoxime (MEKO) are tumorigenic in rodents, inducing liver tumors in male animals. The mechanisms of tumorigenicity for these compounds are not well defined. Oxidation of the oximes to nitronates of secondary-nitroalkanes, which are mutagenic and tumorigenic in rodents, has been postulated to play a role in the bioactivation of ketoximes. In these experiments, we have compared the oxidation of acetoxime and methylethyl ketoxime to corresponding nitronates in liver microsomes from different species. The oximes were incubated with liver microsomes from mice, rats, and several human liver samples. After tautomeric equilibration and extraction with n-hexane, 2-nitropropane and 2-nitrobutane were quantitated by GC/MS-NCI (limit of detection of 250 fmol/injection volume). In liver microsomes, nitronate formation from MEKO and acetoxime was dependent on time, enzymatically active proteins, and the presence of NADPH. Nitronate formation was increased in liver microsomes of rats pretreated with inducers of cytochrome P450 and reduced in the presence of inhibitors (n-octylamine and diethyldithiocarbamate). Rates of oxidation of MEKO (Vmax) were 1.1 nmol/min/mg (mice), 0.5 nmol/min/mg (humans), and 0.1 nmol/min/mg (rats). In addition to nitronates, several minor metabolites were also enzymatically formed (two diastereoisomers of 3-nitro-2-butanol, 2-hydroxy-3-butanone oxime and 2-nitro-1-butanol). Acetoxime was also metabolized to the corresponding nitronate at rates approximately 50% of those observed with MEKO oxidation in the three species examined. 2-Nitro-1-propanol was identified as a minor product formed from acetoxime. No sex differences in the capacity to oxidize acetoxime and MEKO were observed in the species examined. The observed results show that formation of sec-nitronates from ketoximes occurs slowly, but is not the only pathway involved in the oxidative biotransformation of these compounds. Due to the lack of sex-specific oxidative metabolism, other metabolic pathways or mechanisms of tumorigenicity not involving bioactivation may be involved in the sex-specific tumorigenicity of ketoximes in rodents.

The hepatocarcinogenicity of acetoxime has been tentatively linked with its metabolic oxidation to the potent genotoxicant and carcinogen propane 2-nitronate (P2-N). In order to test the hypothesis that acetoxime is metabolized to P2-N, the oxime (20 mM) was incubated with liver microsomes from mice, rats and two humans. Ion-pair HPLC analysis of the incubates afforded a peak that co-eluted with P2-N. P2-N exists in tautomeric equilibrium with 2-nitropropane (2-NP). Samples of the microsomal incubates, which had been adjusted to pH 5.5 and kept for 24 hr in order to allow maximal tautomeric equilibration of P2-N to 2-NP to occur, were extracted with hexane. GLC analysis of the extracts yielded a peak that co-eluted with 2-NP, and gave a mass spectrum identical to that of authentic 2-NP. The metabolite peak obtained on HPLC was isolated and its hexane extract contained also 2-NP when investigated by GLC. P2-N was found by HPLC in the urine of rats that had received acetoxime (3.36 mmol/kg i.p.). Hexane extracts of urine samples, which had been adjusted to pH 5.5 and left for 24 hr, contained 2-NP as demonstrated by GLC analysis. The results are consistent with the suggestion that the toxicity of acetoxime is associated with its biotransformation to P2-N.

Used as a solvent (cellulose ethers), primer (diesel fuels), and intermediate (organic synthesis); [Hawley]

MEDICATION

Organic synthesis (intermediate); solvent for cellulose ethers; primer for diesel fuels.

Derivation: Reaction of hydroxylamine in water solution with acetone, followed by ether extraction.

Prepared by shaking an aqueous solution of hydroxylamine with acetone and extracting with ether.