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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
Neurotoxicity
Administrative data
- Endpoint:
- neurotoxicity: sub-chronic oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1983
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The incidence and severity of findings at other exposure levels was not reported and hence a NOAEL was not identifiable from this study.
Data source
Reference
- Reference Type:
- publication
- Title:
- Neurotoxicity Of Acrylamide And Related Compounds In Rats: Effects On Rotarod Performance, Morphology Of Nerves And Neurotubulin.
- Author:
- Tanii H. and Hashimoto K.
- Year:
- 1 983
- Bibliographic source:
- Arch. Toxicol. 54:203-213.
Materials and methods
- Principles of method if other than guideline:
- Neurotoxicity study in the rat.
- GLP compliance:
- not specified
- Limit test:
- no
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:
- No data
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: not specified
- Age at study initiation: not specified
- Weight at study initiation: not specified
- Fasting period before study: not specified
- Housing: not specified
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: not specified
ENVIRONMENTAL CONDITIONS
- Temperature (°C): not specified
- Humidity (%): not specified
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): not specified
IN-LIFE DATES: not specified
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- Animals were dosed for 60-90 daysin drinking water in four different concentrations (four rats per dose level) chosen by preliminary experiments.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 3.36, 5.41, 8.65, 13.8 mM
Basis:
nominal in water
- No. of animals per sex per dose:
- 4 males
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- 0, 3.36, 5.41, 8.65, 13.8 mM in drinking water for 90 days is equivalent to approximately 0, 33.9, 54.6, 87.4, and 139.4 mg/ml, respectively
Examinations
- Neurobehavioural examinations performed and frequency:
- A modified apparatus of Dunham and Miya (1957), which consists of a 9-cm diameter, roughly surfaced PVC rod, rotated at 5 rpm, was used. Arithmetic means of the walking periods in five successive 60-s trials in each rat measured once a week for 90 days were calculated.
- Sacrifice and (histo)pathology:
- After treatment with the test compounds for 90 days, animals given the highest dose level were injected with heparin (sodium salt, 10,000 U/kg body weight). Thirty minutes later, they were anesthetized with pentobarbital sodium and perfused with 4% paraformaldehyde followed by 5% glutaraldehyde, each in 0.1 M phosphate buffer (pH 7.4), through the left ventricle using a pressure of about 110 mm of mercury. Tissue segments from tibial and sural nerves were immersed for 2 h in 2% Dalton's chrome osmium solution, dehydrated stepwise by ethanol, immersed in propylene oxide, and infiltrated with epoxy resin. The small segments of tissues were placed in molds containing epoxy resin and hardened by heat. Tissue blocks were cut in one micrometer sections and stained with 1% toluidine blue. All epon sections prepared were examined by light microscopy.
[3H]Cholchicine-binding to neurotubulin in nerve tissues: After 60-67 days treatment of animals with each test compound at the highest dose level shown in Table 1, sciatic nerves, brain (cortex and medulla), cerebellum and spinal cord (cervical and lumbar) from both treated and untreated were removed and chilled to 0~C. The binding assay was performed using the method principally the same as Borisy (1972). Tissues were washed with 67 mM phosphate buffer (0.1 M KCI, pH 6.8), homogenzied in the same buffer containing 0.1 mM GTP using a Polytron tissue homogenizer (Kinematica, Luzern, Switzerland) for 30s, and the homogenates were spun at 27,000g for 30 min at 4~C. A 0.1-ml portion of the supernatant (less than 0.3 mg protein) was incubated with 10 ~tlof 0.44 mM [3H]colchicine (specific activity, 0.21 Ci/mmol) at 37~C for 20 min. [3H]-colchicine-binding was linear up to 0.3 mg protein under these conditions. The reaction was stopped by adding 8 ml of ice cold 10 mM phosphate buffer (10 mM MgC12~pH 6.8). The protein was collected on four layers of DE81 Whatman filter discs under low vacuum and washed eight times with 10 ml of the same ice cold buffer. The filters were then placed overnight in a scintillation vial containing fluid (toluene; 2 parts, triton x-100; 1 part, PPO; 5g/l, POPOP; 0.25g/1), and radioactivities were measured in a scintillation counter (Mark III, Searle). - Statistics:
- Body weight differences between the treatment and the control groups were tested for significance using analysis of variance. In other measurements, differences of values were examined using Student's t-test.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Behaviour (functional findings):
- effects observed, treatment-related
- Gross pathological findings:
- not specified
- Neuropathological findings:
- effects observed, treatment-related
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Clinical signs of toxicity included weakness, tendency towards spreading and dragging of hind limbs and occasionally, amongst more severely affected animals, urinary incontinence; however it was not clear which groups these findings were seen in. BODY WEIGHT AND WEIGHT GAIN
Significant reductions in body weight gain was noted amongst all treated animals (6% reduction at the lowest exposure level, 43% at the highest).
WATER CONSUMPTION AND COMPOUND INTAKE (IF DRINKING WATER STUDY)
No data
NEUROBEHAVIOUR
Rotarod performance at day 90 showed impairment only at the two highest exposure levels (3/4 animals at 8.65 mM and 4/4 animals at 13.8 mM). No other rotarod results were available.
NEUROPATHOLOGY
Light microscopy examination showed moderate to severe changes: shrinkage and loss of myelinated fibers, myelin retraction, and corrugation of myelin sheaths. A significant reduction of the colchicine binding was also detected in the spinal cord of both cervical and lumbar regions. However, this reduction in colchicine binding was not seen in the brain or the cerebellum.
OTHER
Significant decreases were observed in the [3H]colchicine-binding in the sciatic nerve at 60 days of treatment.
Effect levels
open allclose all
- Dose descriptor:
- NOAEC
- Effect level:
- 11 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Remarks on result:
- other:
- Dose descriptor:
- LOAEL
- Effect level:
- 17.5 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male
- Remarks on result:
- other:
Applicant's summary and conclusion
- Conclusions:
- N-methylolacrylamide induced neurotoxicity in the rat at 17.5 mg/kg bw/day. The NOAEL was approximately 11 mg/kg bw/day
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