Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 213-103-2 | CAS number: 924-42-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- July 1998-December 2000
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Well documented and scientifically acceptable report conducted to GLP
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 001
- Report date:
- 2001
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
- metabolism
- Principles of method if other than guideline:
- Administration of radioactive NMA to rats and mice followed measurement of absorption, distribution, metabolism and excretion. Air, urine and faeces were collected and assayed for radioactivity. Organs were isolated, weighed and radioactivity content determined. Urinary metabolites were assayed and haemoglobin adducts measured.
- GLP compliance:
- yes
Test material
- Reference substance name:
- N-(hydroxymethyl)acrylamide
- EC Number:
- 213-103-2
- EC Name:
- N-(hydroxymethyl)acrylamide
- Cas Number:
- 924-42-5
- Molecular formula:
- C4H7NO2
- IUPAC Name:
- N-(hydroxymethyl)acrylamide
- Details on test material:
- - Name of test material (as cited in study report): HMA (Hydroxymethyl acrylamide)
- Substance type: organic
- Physical state: solution
- Analytical purity: 98% pure NMA in water
- Impurities (identity and concentrations): not specified
- Isomers composition: not applicable
- Purity test date: not specified
- Lot/batch No.: 5597-62-03 RTI
- Expiration date of the lot/batch:
- Radiochemical purity (if radiolabelling): 100%
- Specific activity (if radiolabelling): 31 μCi/mg
- Locations of the label (if radiolabelling): methylol group
- Expiration date of radiochemical substance (if radiolabelling): not specified
- Stability under test conditions: stable
- Storage condition of test material: not specified
- Other:
Radio-labelled HMA (lot Number CT-9279-39), labelled with carbon-14 in the hydroxymethyl group, was synthesized at RTI. The radiochemical preparation was supplied as a solution in water containing 30 ppm 4-methoxyphenol as a stabilizer. A total of 2.35 mCi was divided equally among 5 ampules each containing about 1 mL of solution. The specific activity of this batch of (14C)NMA was 31 μCi/mg. A second batch of radio-labelled NMA (lot Number CT -9556-15) was synthesized at RTI and had a specific activity of 16 μCi/m. This material was supplied as a solution in water containing 30 ppm 4-methoxyphenol. A total of about 364 μCi was divided equally among 4 ampules.
The radiochemical purity of this material was analysed by HPLC. Following injection of (14C)NMA, the column effluent was collected in fractions. The radioactivity eluting in each fraction was measured by liquid scintillation spectrometry (LSS).
Constituent 1
- Radiolabelling:
- yes
- Remarks:
- Methylol carbon
Test animals
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source:Charles River Labs, Raleigh, NC, USA
- Age at study initiation: 61-75 days
- Weight at study initiation: 19-25 gms
- Fasting period before study: no
- Housing: metabolism cages
- Individual metabolism cages: yes
- Diet: ad libitum
- Watert: ad libitum
- Acclimation period: at least 1 week
IN-LIFE DATES: From: July 1998 To December 2000:
Administration / exposure
- Route of administration:
- other: oral gavage and intraperitoneal
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
VEHICLE
- Justification for use and choice of vehicle (if other than water): water
- Concentration in vehicle: 30 mg NMA/ml
- Amount of vehicle (if gavage): 5 ml/kg
HOMOGENEITY AND STABILITY OF TEST MATERIAL: stable solution - Duration and frequency of treatment / exposure:
- Single gavage and single ip exposures
Doses / concentrations
- Remarks:
- Doses / Concentrations:
150 mg/kg NMA containing 0.88-8.1 μCi radiolabel in both exposure routes
- No. of animals per sex per dose / concentration:
- 4 males
- Control animals:
- no
- Positive control reference chemical:
- No
- Details on study design:
- - Dose selection rationale: not specified
- Rationale for animal assignment (if not random): random - Details on dosing and sampling:
- PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, blood, adipose tissue,brain, epidymis, heart, kidney, liver, lung, muscle, fore-stomach, glandular stomach and cage washes
- Time and frequency of sampling: after 8, 24, 48 and 72 hours for excreta, tissues at sacrifice (72 hours)
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine and red blood cells
- Time and frequency of sampling: after 8, 24, 48 and 72 hours
- From how many animals: 4 per dose, no pooling
- Method type(s) for identification: GC/MS/MS, NMR, HPLC, LSS
- Limits of detection and quantification: not specified - Statistics:
- Mean and standard deviation
Results and discussion
- Preliminary studies:
- None
Main ADME resultsopen allclose all
- Type:
- excretion
- Results:
- 66-77% of radioactivity excreted in urine and CO2 after 72 hours.About 9% was excreted in the faeces.
- Type:
- absorption
- Results:
- Well absorbed based on high percentage of NMA and CO2 recovered in breath and urine and very low recovery in the faeces.
- Type:
- distribution
- Results:
- Blood contained the highest percentage of radioactivity, presumably as the haemoglobin adduct.
- Type:
- metabolism
- Results:
- NMA reacts with glutathione to produce the glutathione adduct across the carbonyl group. No epoxide was found in this study.
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Total excretion 72 hours after oral administration was 79.1±12.3%
42.9±34.6% in urine, 11±1.62% in CO2 and 24.9±22.1% in faeces
Total excretion 72 hours after ip administration was 86.7±4.7%
72.6±7.11% in urine, 9.8±1.12% in CO2 and 4.06±2.9% in faeces - Details on distribution in tissues:
- All organs had a tissue to blood ratio of 0.25-0.56 with adipose and skin on the low end and spleen and kidney on the high end. 25% of the remaining dose was found in the blood.
- Details on excretion:
- Within 24 hours of administration by IP, 60±17% of the administered dose was excreted. For oral administration, 53±19% was excreted in the same period.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- The mercapturate N-acetyl-S-(3-hydroxymethylamino-3-oxopropyl)cysteine, arising from direct conjugation of NMA with glutathione and subsequent metabolism, was the major urinary metabolite. It represented about 41 % of the urinary metabolites after intraperitoneal administration and about 45% of the urinary metabolites (not including parent) after oral administration.
Any other information on results incl. tables
Total Excretion of (14C)NMA
End of collection period | IP Injection | Oral Administration | ||||
% of total dose | % of total dose | |||||
8 hours | 33.2 | ± | 24.2 | 25.0 | ± | 21.6 |
24 hours | 60.1 | ± | 16.9 | 53.2 | ± | 18.7 |
48 hours | 71.6 | ± | 17.1 | 61.8 | ± | 16.3 |
72 hours | 86.7 | ± | 4.7 | 79.1 | ± | 12.3 |
End of collection period | Percent of Dose Recovered for IP Adminsitration | |||||||||||
Urine | Breath Volatiles | CO2 | Faeces | |||||||||
8 hours | 26.3 | ± | 24.0 | 0.01 | ± | 0.00 | 6.56 | ± | 0.65 | - | ||
24 hours | 50.2 | ± | 17.6 | 0.10 | ± | 0.04 | 8.36 | ± | 0.72 | 1.41 | ± | 0.67 |
48 hours | 59.7 | ± | 18.0 | 0.19 | ± | 0.12 | 9.26 | ± | 0.94 | 2.52 | ± | 1.05 |
72 hours | 72.6 | ± | 7.11 | 0.24 | ± | 0.17 | 9.8 | ± | 1.12 | 4.06 | ± | 2.29 |
End of collection period | Percent of Dose Recovered for Oral Adminsitration | |||||||||||
Urine | Breath Volatiles | CO2 | Faeces | |||||||||
8 hours | 18.0 | ± | 21.0 | 0.02 | ± | 0.02 | 6.96 | ± | 1.02 | - | ||
24 hours | 27.8 | ± | 31.4 | 0.13 | ± | 0.07 | 9.00 | ± | 0.88 | 16.3 | ± | 18.4 |
48 hours | 31.0 | ± | 32.8 | 0.25 | ± | 0.10 | 9.85 | ± | 0.95 | 20.7 | ± | 19.2 |
72 hours | 42.9 | ± | 34.6 | 0.33 | ± | 0.11 | 11.0 | ± | 1.62 | 24.9 | ± | 22.1 |
Organ Distribution of (14C)NMA
Tissue | IP Injection | Oral Administration | ||||
% of total dose | % of total dose | |||||
Adipose | 0.29 | ± | 0.19 | 0.15 | ± | 0.06 |
Blood | 0.17 | ± | 0.14 | 0.91 | ± | 0.09 |
Brain | 0.10 | ± | 0.001 | 0.09 | ± | 0.01 |
Epididymis | 0.02 | ± | 0.00 | 0.02 | ± | 0.00 |
Heart | 0.04 | ± | 0.01 | 0.03 | ± | 0.01 |
Kidney | 0.16 | ± | 0.03 | 0.16 | ± | 0.03 |
Liver | 0.39 | ± | 0.10 | 0.35 | ± | 0.06 |
Lung | 0.05 | ± | 0.01 | 0.05 | ± | 0.10 |
Muscle | 1.89 | ± | 0.18 | 1.69 | ± | 0.16 |
Fore-stomach | 0.01 | ± | 0.00 | 0.01 | ± | 0.00 |
Glandular stomach | 0.03 | ± | 0.00 | 0.02 | ± | 0.01 |
Small intestine including contents | 0.20 | ± | 0.02 | 0.23 | ± | 0.06 |
Cecum including contents | 0.05 | ± | 0.01 | 0.10 | ± | 0.09 |
Large intestine including contents | 0.06 | ± | 0.02 | 0.06 | ± | 0.06 |
Skin | 0.56 | ± | 0.1 | 0.44 | ± | 0.07 |
Spleen | 0.02 | ± | 0.01 | 0.02 | ± | 0.00 |
Testis | 0.04 | ± | 0.01 | 0.03 | ± | 0.00 |
TOTAL | 4.77 | ± | 0.29 | 3.74 | ± | 1.09 |
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): no bioaccumulation potential based on study results
NMA administered either intraperitoneally or by gavage to mice at 150 mg/kg was excreted primarily (68-77%) in urine and faeces. About 10% of the radioactivity was excreted as 14CO2 after either route. The high percent of the dose recovered in urine and as CO2 indicates that NMA is well absorbed after either route of administration. Less than 0.5% of the dose was recovered in volatile breath. NMA did not accumulate in any tissue sampled after either route. Less than 5% of the administered radioactivity remained in the tissues sampled 72 h after dosing. The mercapturate, N-acetyl-S-(3-hydroxymethylamino-3-oxopropyl)cysteine, arising from direct conjugation of NMA with glutathione and subsequent metabolism, was the major urinary metabolite. It represented about 41 % of the urinary metabolites after intraperitoneal administration and about 45% of the urinary metabolites·(not including parent) after oral administration. These percentages are similar to those reported by Sumner et a!.(1992) for the amount of mercapturate of acrylamide present in mouse (41%) urine after oral (50 mg/kg) administration.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.