Acetamide

Hazardous Air Pollutants (HAPs)

Nitrogen Compounds -> Other Nitrogen Compounds

Carcinogens

log Kow = -1.26

-1.26

-1.26

-1.05

1.159 at 68 °F (NTP, 1992) - Denser than water; will sink

1.159 at 20 °C/4 °C

1.16 g/cm³

1.159

1.159 @ 20°C

Deliquescent hexagonal crystals

Trigonal monoclinic crystals from alcohol and ether

Very soluble (greater than or equal to 100 mg/mL at 72 °F) (NTP, 1992)

In water, 7.05X10+5 mg/L at 24.5 °C

One gram dissolves in 0.5 mL water, 2 mL alcohol, 6 mL pyridine

Soluble in chloroform, glycerol, hot benzene

Slightly soluble in ether

430 °F at 760 mmHg (NTP, 1992)

222 °C at 760 mm Hg

221.00 to 222.00 °C. @ 760.00 mm Hg

222 °C

430 °F

Warning

H351: Suspected of causing cancer [Warning Carcinogenicity]

P203, P280, P318, P405, and P501 (click each P-code to see the statement)

Warning

H351 (100%): Suspected of causing cancer [Warning Carcinogenicity]

P203, P280, P318, P405, and P501 (click each P-code to see the statement)

Chemical: Acetamide

Hazard Traits - Carcinogenicity; Dermatotoxicity

Status: Active Update: 26-04-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/17464

Acetamide: 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.)

The flash point of this chemical has not been determined, but it is probably combustible. (NTP, 1992)

Combustible. Gives off irritating or toxic fumes (or gases) in a fire.

Acetamide is used primarily as a solvent and a plasticizer. Workers may be exposed in the plastics and chemical industries. It causes mild skin irritation from acute (short-term) exposure. No information is available on the chronic (long-term), reproductive/developmental, or carcinogenic effects of acetamide in humans. EPA has not classified acetamide for carcinogenicity.

There are no human data, but long-term feeding studies in rats using high doses of acetamide (up to 5% in diet) produced liver damage and hepatocellular carcinomas. . . . high doses producing maternal toxicity may cause developmental toxicity. The acute toxicity after ingestion is relatively low: an LD50 of 1000-7000 mg/kg in rats and mice; [ACGIH] A skin and eye irritant; [ICSC]

ACETAMIDE may react with azo and diazo compounds to generate toxic gases. May form flammable gases with strong reducing agents. Reacts as a weak bases (weaker than water). Mixing with dehydrating agents such as P2O5 or SOCl2 generates acetonitrile Burns to give toxic mixed oxides of nitrogen (NOx).

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Acetamide is produced, as an intermediate or a final product, by process units covered under this subpart.

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. Acetamide is included on this list.

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

Use water spray, powder.

Fresh air, rest.

Remove contaminated clothes. Rinse skin with plenty of water or shower.

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Refer for medical attention .

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

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.

Use dry chemical, carbon dioxide, water spray, or alcohol foam extinguishers. ... If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Notify local health and fire officials and pollution control agencies. From a secure, explosion-proof location, use water spray to cool exposed containers. If cooling streams are ineffective (venting sound increases in volume and pitch, tank discolors, or shows any signs of deforming), withdraw immediately to a secure position.

The only respirators recommended for firefighting are self-contained breathing apparatuses that have full face-pieces and are operated in a pressure-demand or other positive-pressure mode.

Keep container tightly closed in a dry and well-ventilated place. Moisture sensitive.

Appropriate engineering controls: 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.

Should be stored in a cool, well-ventilated area. Store in a dry area away from water because of deliquescent properties. Sources of ignition, such as smoking and open flames, are prohibited where this chemical is used, handled, or stored in a manner that could create a potential fire explosion hazard.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

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. 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: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

Evacuate persons not wearing protective equipment from area of spill or leak until cleanup is complete. Remove all ignition sources. Collect powdered material in the most convenient and safe manner and deposit in sealed containers. Ventilate area after cleanup is complete. Material is very water soluble and hydrolyzes slowly to ammonia and acetate salts. May be removed from alkaline solutions with adsorbent carbon. It may be necessary to contain and dispose of this chemical as a hazardous waste. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters.

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a strong soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

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.

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

Product: 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.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for ACETAMIDE (8 total), please visit the HSDB record page.

Personal protection: P2 filter respirator for harmful particles. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting. Carefully collect remainder. Then store and dispose of according to local regulations.

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. 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.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for ACETAMIDE (14 total), please visit the HSDB record page.

Two groups of 40 male wistar rats were fed diets containing 2.5% acetamide or 2.5% acetamide + 5.6 l-arginine, & 2 groups of 15 males were fed diet containing 5.6% arginine glutamate or a control diet for 1 yr. In 2/8 rats fed acetamide ... hepatomas ... were observed; 7/16 rats fed acetamide for 1 yr and maintained on control diet for further 3 MO developed liver tumors. In contrast, 1/11 rats that received acetamide + arginine glutamate for 1 yr and control diet for 3 MO had hyperplastic liver nodules. No liver tumors occurred in control group nor in rats fed 5.6% arginine glutamate alone.

TERRESTRIAL FATE: Based on a classification scheme(1), a Koc value of 5(SRC) indicates that acetamide is expected to have very high mobility in soil(SRC). Volatilization of acetamide from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.0X10-9 atm-cu m/mole(SRC), derived from its vapor pressure, 0.0182 mm Hg(3), and water solubility, 7.05X10+5 mg/L(4). Acetamide is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure. A 69% of theoretical BOD in 2 weeks using activated sludge in the Japanese MITI test(5) and a 69% of theoretical degradation in a 10-day window of an OECD 301D Closed Bottle test(3) indicates that biodegradation is an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), a Koc value of 5(2) indicates that acetamide 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 2.0X10-9 atm-cu m/mole(SRC), derived from its vapor pressure, 0.0182 mm Hg(3), and water solubility, 7.05X10+5 mg/L(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow of -1.26(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). A 69% of theoretical BOD in 2 weeks using activated sludge in the Japanese MITI test(8) and a 69% of theoretical degradation in a 10-day window of an OECD 301D Closed Bottle test(3) indicates that biodegradation is an important environmental fate process in water(SRC). Results of hydrolysis studies indicate the hydrolysis half-life of acetamide at 25 °C and pH 7 is 3,440 to 3,950 years(9,10).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), acetamide, which has a vapor pressure of 0.0182 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere(SRC). Vapor-phase acetamide 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 7.6 days(SRC), calculated from its rate constant of 2.1X10-12 cu cm/molecule-sec at 25 °C(SRC) determined using a structure estimation method(3). Acetamide does not absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: Acetamide is a solid. It is used as a solvent and stabilizer, accelerator in the estimation of bilirubin, antidote against monofluoroacetamide poisoning, and humectant for paper. HUMAN EXPOSURE AND TOXICITY: There are no data available. ANIMAL STUDIES: When acetamide was administered at a concentration of 5% in the diet to 99 male rats, with 2 rats returned to a control diet each week, liver tumors were found after treatment for 14-40 weeks in 22/81 rats. Acetamide-treated rats developed neoplastic nodules and hepatocellular carcinomas. The incidence, speed of onset, and frequency of metastases were greater in males than in females. Acetamide had the least toxic effects in regards to teratogenicity and embryotoxicity, compared to its derivatives. Acetamide produced morphological transformation in Syrian hamster embryo cells without metabolic activation. ECOTOXICITY STUDIES: Acetamide exhibited a selective damaging action on Entosiphon sulcatum.

/AQUATIC SPECIES/ ... In rainbow trout, increase in sperm motility parameters (VAP and MOT) were observed in the presence of acetamide, an inhibitor for beta-N-Acetylglucosaminidase (beta-NAGase). In contrast, sperm motility parameters (VCL, VSL, VAP, MOT, and PRG) were reduced on the Siberian sturgeon in the presence of acetamide. The inhibition of the activity of beta-NAGase in rainbow trout spermatozoa was led to a reduction in the number of fertilized eggs from 79% to 40%, whereas in sturgeon no change was observed in fertilization. Moreover, inhibition of beta-NAGase in both spermatozoa and eggs of trout and sturgeon resulted in significant decrease in fertilization rate from 79% to 1% in rainbow trout and from 84% to 12% in Siberian sturgeon. ...

/AQUATIC SPECIES/ The toxicity threshold using the cell multiplication inhibition test was determined for pseudomonas putida (bacteria), scendesmus quadricauda (green algae) and entosiphon sulcatum (protozoa). Test based on principle that dissolved toxic water ingredients will inhibit multiplication of test organisms as compared to culture free from such influence. Acetamide exhibited a selective damaging action on entosiphon sulcatum.

Redness. Pain.

Redness. Pain.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of September 8, 2016: http://actor.epa.gov/dashboard/]

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page for acetamide, which tabulates all of the "Genetic Toxicology Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from: http://ntp.niehs.nih.gov/testing/status/agents/ts-10375-a.html]

Acetamide was detected at concentrations of 2.4 and 28.6 ug/L in distillate and residue, respectively, in leachate from a landfill for municipal wastes in Japan(1). Acetamide was detected in condensate and process oil-shale retort water at concentrations of 0.6 mg/L and 23.2 mg/L, respectively(2).

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Acetamide is produced, as an intermediate or a final product, by process units covered under this subpart.

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. Acetamide is included on this list.

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 100 lb or 45.4 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV.D.3.b).

Acetamide ... was found in small amt in human urine as metabolite of metronidazole.

Metabolism of metronidazole to acetamide was apparently mediated by intestinal flora.

Acetamide is carcinogenic in rats and mice. To clarify the mechanism of carcinogenesis by acetamide, we investigated DNA damage by andacetamide metabolite, acetohydroxamic acid (AHA), using 32P-5'-end-labeled DNA fragments. AHA treated with amidase induced DNA damage in the presence of Cu(II) and displayed a similar DNA cleavage pattern of hydroxylamine. DNA damage was inhibited by both catalase and bathocuproine, suggesting that H2O2 and Cu(I) are involved. Carboxy-PTIO, a specific scavenger of nitric oxide (NO), partially inhibited DNA damage. The amount of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) by amidase-treated AHA was similar to that by hydroxylamine. ESR spectrometry revealed that amidase-treated AHA as well as hydroxylamine generated NO in the presence of Cu(II). From these results, it has been suggested that AHA might be converted into hydroxylamine by amidase. These results suggest that metal-mediated DNA damage mediated by amidase-catalyzed hydroxylamine generation plays an important role in the carcinogenicity of acetamide.

The volume of distribution was about 1 mL/g, total body clearance was 0.27 mL/min and renal clearance was 0.19 mL/min. Approximately 64 72% of (14)C acetamide was excreted in the urine, while only 0.5 0.8% appeared in exhaled air during the first 6 hr after dosing. Thus, approximately 30% of the administered dose was not recovered and it was suggested that metabolized acetamide enters the acetate pool.

Less than 0.07% of the recovered urinary radioactivity in rats given 100 or 1000 mg/kg bw (14)C acetamide coeluted upon high performance liquid chromatography with an N-hydroxyacetamide standard and this hydroxamic acid could not be detected after incubation of acetamide with rat liver microsomes and NADPH or in primary cultures of rat hepatocytes. (14)C Acetamide does not bind covalently to proteins in the presence of rat liver microsomes and NADPH or cytosolic fraction, whereas hepatocyte cultures contained non extractable radioactivity. This association was inhibited by cycloheximide to the same extent as (14)C acetate incorporation into cellular proteins.

Acetamide is used as a solvent, plasticizer, and a wetting and penetrating agent.

Used as a solvent, plasticizer, stabilizer, humectant for paper, hygroscopic agent, wetting agent, penetrating agent, and denaturant of alcohol; Also used in lacquers, explosives, and soldering fluxes; [HSDB] Used as a solvent in the following applications: plasticizers, lacquers, explosives, soldering flux, wetting agents, and synthesis of other agents; [ACGIH]

Soldering [Category: Heat or Machine]

Solvent; molten acetamide is an excellent solvent for many organic and inorganic compounds. Solubilizer; renders sparingly soluble substances more soluble in water by mere addition or by fusion. Plasticizer; stabilizer. Manufacture of methylamine, denaturing alcohol. In organic synthesis.

Organic synthesis (reactant, solvent, peroxide stabilizer), general solvent, lacquers, explosives, soldering flux, hygroscopic agent, wetting agent, penetrating agent.

It suppresses acid buildup in printing inks, lacquers, explosives, and perfumes. It is a mild moisturizer and is used as a softener for leather, textiles, paper, and certain plastics. ... Acetamide and substituted acetamide-containing thiourea can be used for treatment of herpes viruses. Derivatives can also be used as feeding behavior modifiers.

Prepared by fractional distillation of ammonium acetate.

Interaction of ethyl acetate and ammonium hydroxide.

Acetamide can be produced by several methods. Ammonia reacts vigorously with acetyl halides or acetic anhydride to produce acetamide. Alkyl acetates also react with ammonia to yield acetamide. Dehydration of ammonium acetate is the standard procedure for preparation of acetamide. Finally, acetonitrile is hydrolyzed to yield acetamide in the presence of an acid or base catalyst.

In 1963 ... available in USA as technical grade (99% minimum acetamide and 0.3% maximum free acid) and as chemically pure, odorless grade (99.5-99.9% acetamide and trace of free acid).

Grades: Technical; CP /chemically pure: a grade designation signifying a minimum of impurities, but not 100% purity/ (odorless); intermediate; reagent.