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EC number: 204-826-4 | CAS number: 127-19-5
- 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
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- Auto flammability
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- Stability in organic solvents and identity of relevant degradation products
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- Stability: thermal, sunlight, metals
- pH
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- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
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- Endpoint summary
- Stability
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- 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
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- 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

Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- chronic toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- The study is comparable to Guideline with acceptable restrictions (only 2 animals per dose; limited parameters in hematology and clinical chemistry; limited documentation of urinalysis; only 3 organs examined in histopathology [liver, kidney, skin]; partly limited documentation [details on test substance, analytical results or animals]).
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 961
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 452 (Chronic Toxicity Studies)
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- N,N-dimethylacetamide
- EC Number:
- 204-826-4
- EC Name:
- N,N-dimethylacetamide
- Cas Number:
- 127-19-5
- Molecular formula:
- C4H9NO
- IUPAC Name:
- N,N-dimethylacetamide
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- - Name of test material: dimethylacetamide (DMAC)
No details available.
Test animals
- Species:
- dog
- Strain:
- not specified
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No details available.
Administration / exposure
- Type of coverage:
- open
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- The dose was applied to the shaved skin. Licking was prevented.
REMOVAL OF TEST SUBSTANCE
- Washing: After 5 hours of exposure. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- a) 6 months at the two lower dose levels
b) 6 weeks at the two higher dose levels - Frequency of treatment:
- Once daily for 5 h (washing); 5 days per week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0.1 other: mL/kg bw/day
- Remarks:
- 94 mg/kg bw/day
- Dose / conc.:
- 0.32 other: mL/kg bw/day
- Remarks:
- 300 mg/kg bw/day
- Dose / conc.:
- 1 other: mL/kg bw/day
- Remarks:
- 940 mg/kg bw/day
- Dose / conc.:
- 4 other: mL/kg bw/day
- Remarks:
- 3760 mg/kg bw/day
- No. of animals per sex per dose:
- a) 2 (1 m, 1 f) in the two low dose groups plus control
b) 2 males in the two high dose groups plus control - Control animals:
- other: yes, unspecified
- Details on study design:
- - Post-exposure recovery period in satellite groups: Presumably no post exposure observation period.
- Positive control:
- No
Examinations
- Observations and examinations performed and frequency:
- CLINICAL SIGNS:
Clinical signs were recorded (no details).
BODY WEIGHT:
The animals were weighed at weekly intervals.
HEMATOLOGY:
- Time schedule for collection of blood: Initial and after 1, 2, 3, 6 months in a) (no details), weekly in b).
- Parameters examined: Hemoglobin, sedimentation rate, hematocrit, total and differential white blood cell counts.
CLINICAL CHEMISTRY:
- Time schedule for collection of blood: Initial and after 1, 2, 3, 6 months in a) (no details), weekly in b).
- Parameters examined: Blood urea nitrogen (BUN), bromsulphthalein (BSP) dye retention, thymol turbidity, alkaline phosphatase.
URINALYSIS:
Urine analysis was performed but no details given . - Sacrifice and pathology:
- GROSS PATHOLOGY:
Gross autopsies were performed upon the animal that died and on the remaining animals sacrificed at termination of the study.
HISTOPATHOLOGY:
Sections of liver, kidney and skin were processed and examined. - Other examinations:
- No
- Statistics:
- No data
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Anorexia, depression, weakness, ataxia, abdominal tenderness, diarrhea and frank jaundice were present in the dogs on the 4 mL/kg bw/day level just prior to death
- Dermal irritation:
- effects observed, treatment-related
- Description (incidence and severity):
- No significant microscopic findings were seen in the skin at 0.1 mL, except for slight thickening and/or inflammatory reaction.
Local effects (ulcer) were observed in 1/2 dogs at 0.32 mL/kg bw/day after 4 month. Administration to this site was stopped, and the ulcer gradually healed over a period of 1 month . The skin of both dogs showed marked scaliness.
Mild to moderate skin irritation at ≥ 1 mL/kg bw/d (at termination of the studies the dogs showed fissuring and thick scales, which resembled eschars). - Mortality:
- mortality observed, treatment-related
- Description (incidence):
- At 4 mL/kg bw/day one dog died after 15 applications and the other was sacrificed moribund at day 16.
At 1 mL/kg bw/day both dogs were sacrificed moribund after 6 weeks of treatment. - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Dogs at both high dose levels showed weight loss. At 0.32 mL/kg bw/d there was reduced body weight during the initial exposure period.
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- At ≥1.0 mL/kg bw/d there was increased hematocrit and hemoglobin, and leukocytosis.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- At ≥0.32 mL/kg bw/d the activity of alkaline phosphatase was increased. There was altered BSP retention.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Pale or yellow liver was noted at necropsy.
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Fatty degeneration of the liver was noted at ≥1 mL/kg bw/day (940 mg/kg bw/day); there were no effects noted in the kidneys.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 0.1 other: mL/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects observed at this dose
- Remarks on result:
- other: 94 mg/kg bw/day
- Dose descriptor:
- LOAEL
- Effect level:
- 0.32 other: mL/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical biochemistry
- gross pathology
- Remarks on result:
- other: 300 mg/kg bw/day
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- In chronic studies toxic effects were detected in dogs after dermal exposure to DMAC at dose levels >=300 mg/kg bw/day. The dermal NOAEL was 94 mg/kg bw/day.
- Executive summary:
In a chronic dermal toxicity study comparable to guideline (OECD TG 452) 2 dogs per dose level received 0, 0.10, 0.32, 1.0, or 4.0 mL/kg bw/day corresponding to 0, 94, 300, 940, 3760 mg/kg bw/day to clipped skin. The dermal exposure was conducted openly with washing after 5 h exposure at 5 days per weeks. The exposure period was 6 weeks for the two higher dose levels (lethal effects) and 6 months for the two lower dose levels.
Mortality was observed at the two higher dose levels; dogs died or were sacrificed moribund (after 6 weeks at 1 mL/kg bw/day). At a dose level of 0.32 mL/kg bw/day local effects (ulcer), decrease in body weight, increased activity of alkaline phosphatase, and altered BSP retention were seen. Fatty degeneration of the liver was detected in histopathology at >=1 mL/kg bw/day (940 mg/kg bw/day). No data were available on histopathology of the testes (compare with other repeated dose studies in mouse and rat).
Conclusion: The dermal NOAEL was 94 mg/kg bw/day.
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