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EC number: 679-769-5 | CAS number: 2675-94-7
- 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:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- THE DISTRIBUTION AND METABOLISM OF ACRYLAMIDE AND ITS NEUROTOXIC ANALOGUES IN RATS
- Author:
- Edwards PM
- Year:
- 1 975
- Bibliographic source:
- Biochemical Pharmacology, Vol. 24, pages 1277-1282
- Report date:
- 1975
Materials and methods
- Objective of study:
- distribution
- metabolism
Test guideline
- Qualifier:
- no guideline followed
Test material
- Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- other: Porton
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Body weight: 200 + 20 g
Administration / exposure
- Route of administration:
- intravenous
- Vehicle:
- other: 60% m-dioxan-5-ol in water
- Details on exposure:
- (176 mg/kg) were given intravenously in 60% m-dioxan-5-ol in water. The volume of each solution injected was 1 mL/kg.
- Duration and frequency of treatment / exposure:
- Single intravenous dose
Doses / concentrations
- Dose / conc.:
- 176 mg/kg bw/day (actual dose received)
- Details on dosing and sampling:
- - Detection of acrylic amides: paper chromatograms
- Assay of free acrylamide and N-hydroxymethylacrylamide in blood: Rats were aesthetized with ether and 2 mL blood removed from the posterior vena cava into a heparinized syringe. Blood (1 mL) was mixed with 3 mL methanol containing Tris(hydroxymethyl)-aminomethane (0.1% w/v). The clear supernatant obtained after centrifugation of the extract in a bench centrifuge for 15 min was assayed.
- Paper chromatography of blood extracts: Samples (100µL) were applied to Whatman No. 1 chromatography paper. Papers were developed by descending chromatography for 16 hr at 25 ° using 60mL butanol saturated with water.
- Assay of free glutathione in the liver: All rats were starved from the time of dosing until the livers were removed in order to avoid any effect of changes in food consumption on liver glutathione. The livers were homogenized in 11 vol. buffered ethanol. The homogenate was centrifuged at 2500 g for 20 min and the supernatant assayed for glutathione.
- Identification of the glutathione conjugates of acrylamide and N-hydroxymethylacrylamide in extracts of liver and bile: Ethanolic extracts of liver were applied to Whatman No.1 chromatography paper after concentration by rotary evaporation. Bile was collected by cannulation of the bile duct close to the duodenum and applied directly to Whatman No. 1 chromatography paper.
- Separation of the glutathione conjugates of acrylamide and N-hydroxymethylacrylamide from bile by ion-exchange chromatography: Bile (1.5 mL) was applied directly to ion-exchange columns (15.5 x 0.9 cm) of acetate resin and washed on with 1 mL water. The column was eluted with 120mL 0.1 N acetic acid followed by 0.22 N acetic acid. The glutathione conjugates of acrylamide eluted in the same volume, between 120 and 190mL. The concentration of glutathione conjugates in the eluate was assayed with ninhydrin.
- Estimation of specific radioactivity of glutathione conjugates: The radioactivity was measured by scintillation counting in Instagel. Efficiency of counting was estimated by internal standardization. The chemical and radiochemical purity of all fractions was checked by paper chromatography.
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on distribution in tissues:
- - Concentration of acrylamide and N-hydroxymethylacrylamide in blood after intravenous dosing: The blood concentrations fell exponentially after intravenous dosing. The half-life for test item is 1.55 hr. Extrapolation of the decay curve back to zero time gives a concentration very close to the theoretical value for dilution in total body water.
- Identification of acrylamide in the blood of rats dosed with acrylamide analogues: Chromatography of methanolic extracts of blood of rats 0.5 and 1 hr after dosing rats with either N-methylacrylamide or test item indicated that neither acrylamide nor N-hydroxymethylacrylamide had been formed. A 5 percent molar conversion to acrylamide or N-hydroxymethylacrylamide could have been detected.
Metabolite characterisation studies
- Details on metabolites:
- - Concentration of glutathione in the liver after dosing: The liver glutathione fell rapidly, reaching a minimum of about 36 per cent normal values between 2 and 4 hr, then returned to normal, or slightly higher than normal concentration by 24 hr. There was little diurnal variation even in fed rats. Dosing causes a loss of glutathione from the liver. The reaction products of test item with liver glutathione are very rapidly excreted in the bile.
Applicant's summary and conclusion
- Conclusions:
- Test item distributed throughout total body water within a few minutes. The concentrations of compound decreased exponentially after this initial distribution, with a half-life of less than 2 hr. The compound caused a rapid decrease in liver glutathione in vivo, and the glutathione conjugates were excreted in the bile.
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