Glycidamide

87.08

87.08

227-163-2

DTXSID2031374

2924299090

55.6

-0.63 (est)

1.4±0.1 g/cm3

33-34 °C

72-73 °C @ Press: 0.2 Torr

240.8±21.2 °C

1.516

In water, 4.3X10+5 mg/L at 25 deg C (est)

Hygroscopic, -20°C Freezer, Under Inert Atmosphere

0.586 mm Hg at 25 deg C (est)

mic-bac-sat 500 mg/plate MUREAV158,129,85

Henry's Law constant = 1.29X10-10 atm-cu m/mole at 25 °C (est)

When heated to decomposition, it emits toxic vapors of NOx|Hydroxyl radical reaction rate constant = 2.6X10-12 cu cm/molec-sec at 25 °C (est)

NONH for all modes of transport

3

45-46-22-36/37/38-43

53-26-36/37-45

MB3200000

T

P201-P261-P280-P305 + P351 + P338-P308 + P313

H302-H315-H317-H319-H335-H350

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity 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 and plant life; and conformance with environmental and public health regulations.|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. Contact a licensed professional waste disposal service to dispose of this material.

Materials to avoid: Incompatible with strong bases and oxidizing agents.

FAO/WHO; Consultation on the Health Implications of Acrylamide in Food, Summary Report (June 2002).[Available from, as of March 1, 2010: http://ntp.niehs.nih.gov/ntp/htdocs/Chem_Background/ExSumPdf/Acrylamide.pdf]|DHHS/CDC; Fourth National Report on Human Exposure to Environmental Chemicals (2009). The Report is a comprehensive assessment of the exposure of the U.S. population to chemicals in our environment.[Available from, as of March 4, 2010: http://www.cdc.gov/exposurereport/]|WHO/IARC; IARC Monographs on the Evaluation of the Carcinogenic Risks to Humans. Vol. 60. Some Industrial Chemicals (1994). IARC Monographs provide critical reviews of data on carcinogenicity for agents to which humans are known to be exposed and on specific exposure situations.[Available from, as of March 4, 2010: http://monographs.iarc.fr/ENG/Monographs/vol60/index.php]

|Danger|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P261, P264, P270, P271, P272, P280, P281, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P330, P332+P313, P333+P313, P337+P313, P362, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 38 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H340: May cause genetic defects [Danger Germ cell mutagenicity]|P201, P202, P260, P264, P270, P281, P308+P313, P314, P405, and P501

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P2 (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).|Hand protection: Handle with gloves. The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and the standard EN 374 derived from it.|Eye protection: Safety glasses.|Skin and body protection: Choose body protection according to the amount and concentration of the dangerous substance at the work place.|Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.

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

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.|Personal precautions: Use personal protective equipment. Avoid dust formation. Avoid breathing dust. Ensure adequate ventilation. Evacuate personnel to safe areas.|Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains.|Methods for cleaning up: Pick up and arrange disposal without creating dust. Keep in suitable, closed containers for disposal.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.|Handling: Avoid exposure - obtain special instructions before use. Avoid formation of dust and aerosols.|In case of skin contact: Wash off with soap and plenty of water. Consult a physician.|In case of eye contact: Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.|Hygiene measures: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.

Irritating to eyes, respiratory system and skin.

Glycidamide has been identified as a hemoglobin adduct of acrylamide(1), a chemical intermediate used in the production of polymers targeted as additives for water treatment(2) and that also occurs in some cooked foods(3); this may result in glycidamide's release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1(SRC), determined from a structure estimation method(2), indicates that glycidamide is expected to have very high mobility in soil(SRC). Volatilization of glycidamide from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.29X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Glycidamide is expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 0.586 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradation data were not available(SRC, 2010).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1(SRC), determined from a structure estimation method(2), indicates that glycidamide 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 1.29X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow of -0.63(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2010).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), glycidamide, which has an estimated vapor pressure of 0.586 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 glycidamide 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 6 days(SRC), calculated from its rate constant of 2.6X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Glycidamide 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).

The rate constant for the vapor-phase reaction of glycidamide with photochemically-produced hydroxyl radicals has been estimated as 2.6X10-12 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 6 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Glycidamide contains an epoxide functional group that may hydrolyze under environmental conditions(2); however, an estimated base-catalyzed second-order hydrolysis rate constant of 1.22X10-5 L/mole-sec(SRC) was estimated using a structure estimation method(2) which corresponds to a half-life of 1.795X10+4 years at pH 7(3). Glycidamide does not contains chromophores that absorb at wavelengths >290 nm(2), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for glycidamide(SRC), using an estimated log Kow of -0.63(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).

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

The Henry's Law constant for glycidamide is estimated as 1.29X10-10 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that glycidamide is expected to be essentially nonvolatile from water surfaces(2). Glycidamide is expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 0.586 mm Hg(SRC), determined from a fragment constant method(3).

The metabolic precursor of glycidamide, acrylamide, occurs in many carbohydrate-containing foods cooked at high temperatures such as French fries, potato chips, pretzels, coffee, breads, and cereals(1,3). Acrylamide is rapidly absorbed after dietary exposure and readily crosses the blood-brain barrier(2).

Biomonitoring study results indicate that the general population may be exposed to glycidamide as a result of ingestion of certain cooked foods(1) and treated drinking water containing acrylamide, which is then metabolized to glycidamide as a hemoglobbin adduct in the body(2).

The geometric mean concentration of hemoglobin adduct glycidamide concentrations for the US population determined from the National Health and Nutrition Examination Survey (NHANES) is 59.3 pmol/g hemoglobin. The sample size was 7,278 and sampling was conducted from 2003 to 2004(1).

The formation of glycidamide and acrylamide adducts on the N-terminal valine of hemoglobin (Hb) is directly proportional in man and rat. Comparison of free acrylamide in plasma, valine adducts on Hb and urinary S-(2-carboxyethyl)cysteine indicate that the rate of elimination of acrylamide is at least five times lower in man than in rats. Therefore, since the integrated concentration-time ratio for glycidamide to acrylamide adducts in man (0.3) is about one-half of that for rats (0.58) at low doses, the tissue dose of glycidamide may be higher in man than in rats, on the basis of an equal uptake of acrylamide.|Physiologically-based toxicokinetic ("pharmacokinetic") (PBPK or PBTK) modeling can be used as a tool to compare internal doses of acrylamide (AA) and its metabolite glycidamide (GA) in humans and rats. ... Excellent fits to a majority of the data for male Fischer 344 rats were obtained. Kinetic parameters for the human model were estimated based on fit to available human data for urinary metabolites of AA, and levels of hemoglobin adducts of AA and GA measured in studies in which human volunteers ingested known doses of AA. The simulations conducted with the rat and human models predicted that rats and humans ingesting comparable levels of AA (in mg/kg/day) would have similar levels of GA in blood and tissues. This finding stands in contrast to the default approach that assumes a 3.2-fold increase in human risk due to pharmacokinetic differences between rats and humans...|... This study used dual recirculating human placental perfusion to determine the transfer rate through the placenta of ... acrylamide and its genotoxic metabolite glycidamide. ... Placentas were collected immediately after delivery and kept physiologically functional as confirmed by antipyrine kinetics, glucose consumption and leak from fetal to maternal circulation. Acrylamide (5 or 10 ug/mL) or glycidamide (5 ug/mL), both with antipyrine (100 ug/mL), was added to maternal circulation. ... Acrylamide and glycidamide crossed the placenta from maternal to fetal circulation with similar kinetics to antipyrine, suggesting fetal exposure if the mother is exposed. The concentrations in maternal and fetal circulations equilibrated within 2 hr for both studied compounds and with both concentrations. Acrylamide metabolism into glycidamide was not detected during the 4-hr perfusions. Moreover, DNA adducts were undetectable in the placentas after perfusions...|The objective of this study was to compare the metabolism of acrylamide (AM) administered orally (po), dermally, intraperitoneally (ip), or by inhalation, and to measure the hemoglobin adducts produced. Rats and mice were exposed to 2.9 ppm (1,2,3-13C) and (2,3-14C)AM for 6 hr. (2,3-14C)AM (162 mg/kg) or (1,2,3-13C)AM (13 8 mg/kg) in water was administered dermally to rats for 24 hr, and (1,2,3-13C)AM was administered ip (47 mg/kg). Urine and feces were collected for 24 hr. Urine was the major elimination route in rats (ip, 62% and po, 53% of the dose; dermal, 44% of the absorbed dose; inhalation, 31% of the recovered radioactivity) and mice (inhalation, 27% of the recovered radioactivity). ... AM-GSH was a major metabolic route in rats accounting for 69% (ip), 71% (po), 52% (dermal), and 64% (inhalation). In mice, AM-GSH accounted for only 27% (inhalation) of the total urinary metabolites. The remaining urinary metabolites were derived from GA. Valine hemoglobin adducts of AM and GA were characterized using liquid chromatography-mass spectrometry. The ratio of AM to GA adducts paralleled the flux through pathways based on urinary metabolites. This study demonstrates marked species differences in the metabolism and internal dose (Hb-adducts) of AM following inhalation exposure and marked differences in uptake comparing dermal with po and ip administration.|... 110 5-6-year-old children were randomly selected. Their dietary habits as well as their exposure to the environmental tobacco smoke were assessed by means of a questionnaire. By means of spot urine samples, mercapturic acids of acrylamide (AAMA) and mercapturic acids of glycidamide (GAMA) were analyzed with LC-ESI-MS/MS. Median (95th percentile) urinary levels were 36.0 (152.7) ug AAMA/L and 13.4 (55.9) ug GAMA/L. Based on the metabolite levels, the median uptake of acrylamide was calculated to be 0.54 ug/kg BW/d. A number of associations with the consumption of French fries, various potato products, as well as fried cereals could be found...

The major metabolite formed via the cytochrome P450 pathway is glycidamide. Species differences in the formation of this metabolite have been observed, with acrylamide converted to glycidamide to a greater extent in the mouse than in the rat, based on urinary metabolites.|In vivo metabolite of acrylamide in rats.|When acrylamide was administered to rats, the conversion to glycidamide was 51% following the administration of 5 mg/kg and decreased to 13% after 100 mg/kg, based on the measurement of hemoglobin adducts. The conversion of acrylamide to glycidamide was higher following subchronic dosing as well. Acrylamide hemoglobin adduct formation was approximately 2- or 4.5-fold greater for oral (20 mg/kg/day for 15, 21, 34 or 47 days) or intraperitoneal (50 mg/kg/day for 11 days) dosing, respectively, than glycidamide adduct formation. Oral administration resulted in approximately 30% fewer acrylamide adducts than intraperitoneal dosing; however, more glycidamide adducts were formed after oral dosing. The authors suggested that the reason for these differences was due to a higher conversion of acrylamide to glycidamide following oral dosing, when compared with intraperitoneal dosing.|The conversion of acrylamide to glycidamide is saturable, ranging from 50% at very low doses to 13% at 100 mg/kg bw in treated rats. Both agents are detoxified by glutathione conjugation, and glycidamide is also detoxified by hydrolysis. Both agents react directly with hemoglobin in vivo, but DNA adducts result only from the formation of glycidamide.|For more Metabolism/Metabolites (Complete) data for Glycidamide (14 total), please visit the HSDB record page.

Acrylamide is metabolized in vitro and in vivo in mice, rats and humans to the epoxide, glycidamide. Both substances are equally distributed throughout the tissues and have half-lives of about 5 hr in rats.|The estimated plasma half-life for acrylamide and glycidamide following oral (20 mg/kg) or intraperitoneal (50 mg/kg) administration in male Sprague Dawley rats was approximately 2 hours for both acrylamide and glycidamide following single or repeated exposures.

2'-Deoxyadenosine (dA) and 2'-deoxyguanosine (dG) were reacted with mutagenic epoxide glycidamide (GA). The reactions yielded three GA-dA adducts (N1-GA-dA, N6-GA-dA and N1-GA-dI) and two GA-dG adducts (N1-GA-dG I and N1-GA-dG II). The structures of the adducts were characterized by spectroscopic and spectrometric methods (1H-, 13C, and 2D NMR, MS, UV). The mechanism of the amide hydrolysis taking place during formation of the adducts N1-GA-dA and N1-GA-dG I was studied. A mechanism where a transamidation is the key step in the hydrolysis of the amide function of GA /was proposed/.

/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 /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's 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/

/HUMAN EXPOSURE STUDIES/ ln a study in China, hemoglobin (Hb) adducts of acrylamide and glycidamide were determined in 41 workers who were exposed to acrylamide for periods ranging between one month and 11.5 years and who had concurrent medical and neurological examinations. The levels of N-terminal valine adducts of acrylamide ranged from 0.3 to 34 nmol/g Hb, with directly proportional formation of glycidamide adducts to the same residue in Hb. Background levels of valine adducts in Hb were not found in a group of 10 controls, with one possible exception, indicating that endogenous production of or environmental contamination with acrylamide is low or nonexistent. The average ratio between the doses of glycidamide and acrylamide received (the concentration of free electrophilic agents integrated over time) in this group of workers was found to be 0.3. On the basis of the Hb adduct levels and the air concentrations in two of the workshops in this study (1.1 and 3.3 mg/cu m) and assuming 100% uptake of acrylamide through the air and an alveolar ventilation rate of 0.2 L/min per kg, it was concluded that there had been only minor exposure by inhalation and that dermal uptake was the dominant route of exposure.|/SIGNS AND SYMPTOMS/ May be harmful if inhaled. Causes respiratory tract irritation. May be harmful if absorbed through skin. Causes skin irritation. Causes eye irritation. Harmful if swallowed|/BIOMONITORING/ Acrylamide and glycidamide hemoglobin adducts (AHA and GHA, respectively) are markers of integrated acrylamide exposure over the preceding few months. Adducts are formed when either acrylamide or glycidamide react to form a permanent covalent bond with hemoglobin in the blood. After exposure ceases, levels of AHA adducts decline but may remain detectable for several months ... AHA levels have been shown to increase with dietary intake ... and smoking ... Levels of AHA and GHA reported /in/ the NHANES 2003-2004 sample are generally similar to those seen in several previous studies of non-occupationally exposed subjects ... , although different analytic methods can affect results. Several of these studies have shown that smokers have adduct levels that are three to fourfold higher than non-smokers; most non-smokers had levels less than about 100 pmol/g hemoglobin. The degree of formation of the more toxic glycidamide and levels of GHA can be influenced by polymorphisms in several of the enzymes that metabolize acrylamide ... Younger children may have slightly higher levels possibly due to increased intake of acrylamide-containing foods relative to body size.|/BIOMONITORING/ A study comprising 50 subjects investigated the relationship between acrylamide (AA) intake from food using food frequency questionnaires and the concentration of hemoglobin (Hb) adducts of AA and its genotoxic metabolite glycidamide (GA) as a measure of the internal exposure. ... Using multiple linear regression analysis, a significant positive correlation was found between the AA-Hb adduct concentration and the intake of chips/snacks and crisp bread. GA-Hb adduct did not correlate with consumption of any of the main food groups. Neither AA-Hb nor GA-Hb adduct concentration correlated with total dietary intake of AA as calculated from the reported food intake. Adduct concentrations did not correlate with 24 hr urinary excretion of mercapturic acid metabolites of AA and GA in the same subjects reported previously.|For more Human Toxicity Excerpts (Complete) data for Glycidamide (11 total), please visit the HSDB record page.

(+--)-oxiranecarboxamide

Alkyl mercury compounds have been used as seed disinfectants and for fungicides. They have also been used in organic synthesis. /Mercury alkyl compounds/

On the basis of a stable isotope dilution assay and derivatization with 2-mercaptobenzoic acid, the presence of glycidamide in processed foods was verified.|A hydrophilic interaction liquid chromatography tandem mass spectrometry method (HILIC-MS/MS) using a zwitterionic stationary phase (Zic-HILIC) was developed and validated to quantitate the mercapturic acids of acrylic acid (AA; AAMA) and glycidamide (GAMA), and AAMA-sulfoxide in human urine.