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EC number: 206-992-3 | CAS number: 420-04-2
- 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
Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1996
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- Stability, homogeneity and correctness of the concentrations not verified analytically; 3 males and 3 females used per concentration instead of 5 males and 5 females; no sacrifice immediately after end of application, but after 14-day; body weight 1200 g ± 200 g instead of 2000 – 3000 g at the beginning of treatment; housing temperature 24 ± 2 °C instead of 20 ± 3 °C; no summary or individual data of clinical findings; less haematological and blood chemistry parameter compared to OECD 410; no individual organ weight data were submitted.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 996
- Report date:
- 1996
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: Gaitonde Committee guidelines
- Deviations:
- no
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Cyanamide
- EC Number:
- 206-992-3
- EC Name:
- Cyanamide
- Cas Number:
- 420-04-2
- Molecular formula:
- CH2N2
- IUPAC Name:
- cyanamide
- Test material form:
- other: aqueous solution
- Details on test material:
- - Test substance: Dormex (Hydrogen cyanamide, aqueous solution)
- Physical state and appearance: Light blue coloured, liquid
- Purity: 50 % w/w formulation
- Lot/Batch number: 507401
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Body weight: 1200 ± 200 g
- Housing temperature: 24 ± 2 °C
Administration / exposure
- Type of coverage:
- not specified
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- Not indicated
- Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- No analytical verification of doses or concentrations was performed
- Duration of treatment / exposure:
- six hours per day on 5 days per week for three consecutive weeks followed by a 14 day post-application observation period.
- Frequency of treatment:
- Daily treatment
Doses / concentrationsopen allclose all
- Dose / conc.:
- 25 mg/kg bw/day (nominal)
- Remarks:
- equivalent to 12.5 mg/kg bw/day active substance Cyanamide
nominal per unit body weight
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- Remarks:
- equivalent to 25 mg/kg bw/day active substance Cyanamide
nominal per unit body weight
- Dose / conc.:
- 75 mg/kg bw/day (nominal)
- Remarks:
- equivalent to 37.5 mg/kg bw/day active substance Cyanamide
nominal per unit body weight
- No. of animals per sex per dose:
- 3 animals per sex per dose
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - The concentrations were selected according to the results of a pilot study
- Positive control:
- No positive control
Examinations
- Observations and examinations performed and frequency:
- The animals were examined once daily for mortalities, clinical symptoms and local skin irritations. Data of body weight and food consumption of individual rabbits were recorded weekly. Clinical-chemical and haematological investigation and urinalysis were performed on day 0, 22 and 35.
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Other examinations:
- No other examinations
- Statistics:
- The difference between the control groups and the test-dose groups were examined by the Student´s test criteria, p< 0.05.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Dermal irritation:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- There were no mortalities in any groups of the test material or post-application observation period. At the highest concentration severe erythema of the skin and reduction in the fur density around the areas of application were observed. Slight erythema during the application period were observed at the mid dose of 25 mg/kg bw/day pure active substance cyanamide which recovered one day after application. There were no significant differences in the body weight and feed consumption of animals treated with Dormex when compared to the control animals. None of the haematological, clinical chemical and urine parameters of the treated groups showed any statistical significant variation as compared to the controls at each time of measurement.
After the recovery period some organ weights revealed a statistical significance in the low, mid or high dose males. However, due to the fact that there are no consistent dose-dependent changes the findings are considered to be incidental.
The gross pathological and histopathological examinations showed no consistent findings in the low and mid dose animals. Some high dose animals showed findings even after the 14 d recovery period.
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 25 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- gross pathology
- histopathology: non-neoplastic
- mortality
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
- Lowest effective dose / conc.:
- 37.5 mg/kg bw/day (nominal)
- System:
- other: histopathological examinations revealed lesions in several tissues/organs, no clear target system
Any other information on results incl. tables
Table 1: Subacute (21-Day) dermal toxicity study in Rabbits: Organ Weights
Pure active ingredient cyanamide | 0 mg/kg bw/day | 12.5 mg/kg bw/day | 25.0 mg/kg bw/day | 37.5 mg/kg bw/day |
Males: |
|
|
|
|
Absolute heart weight (g) | 3.925 | 3.058* | 3.848 | 3.041* |
Relativeaheart weight ( %) | 0.257 | 0.162 | 0.226 | 0.171 |
Absolute liver weight (g) | 31.667 | 45.333* | 58.000* | 45.667* |
Relativealiver weight ( %) | 2.074 | 2.410 | 3.433* | 2.566 |
Absolute kidney weight – left (g) | 5.315 | 3.897** | 5.207 | 4.165** |
Relativeakidney weight – left ( %) | 0.347 | 0.208** | 0.307 | 0.234 |
Absolute kidney weight – right (g) | 5.515 | 4.230* | 5.137* | 4.206* |
Relativeakidney weight – right ( %) | 0.360 | 0.226** | 0.303 | 0.236** |
Absolute gonad weight – left (g) | 0.917 | 1.620 | 1.064 | 2.099 |
Relativeagonad weight – left ( %) | 0.059 | 0.086 | 0.063 | 0.118* |
Absolute gonad weight – right (g) | 0.929 | 1.587* | 1.254 | 2.095 |
Relativeagonad weight – right ( %) | 0.060 | 0.084 | 0.068 | 0.118* |
Females: |
|
|
|
|
Absolute heart weight (g) | 4.383 | 2.941 | 4.329 | 3.310 |
Relativeaheart weight ( %) | 0.261 | 0.153 | 0.217 | 0.180 |
Absolute liver weight (g) | 41.000 | 48.333 | 54.000 | 39.667 |
Relativealiver weight ( %) | 2.480 | 2.521 | 2.704 | 2.152 |
Absolute kidney weight – left (g) | 4.950 | 3.819 | 4.777 | 3.847 |
Relativeakidney weight – left ( %) | 0.290 | 0.200 | 0.241 | 0.209 |
Absolute kidney weight – right (g) | 4.775 | 3.739 | 4.856 | 4.215 |
Relativeakidney weight – right ( %) | 0.280 | 0.196 | 0.245 | 0.230 |
Absolute gonad weight – left (g) | 0.178 | 0.119 | 0.172 | 0.185 |
Relativeagonad weight – left ( %) | 0.010 | 0.006 | 0.009 | 0.010 |
Absolute gonad weight – right (g) | 0.187 | 0.137 | 0.187 | 0.173 |
Relativeagonad weight – right ( %) | 0.011 | 0.007 | 0.010 | 0.009 |
Table 2: Subacute (21-Day) dermal toxicity study in Rabbits: Gross pathological lesions
Pure active ingredient cyanamide (mg/kg bw/day) | 0 | 12.5 | 25 | 37.5 |
Number of rabbits/group | 3 | 3 | 3 | 3 |
Males: |
|
|
|
|
Skin |
|
|
|
|
Alopecic | 0 | 0 | 1 | 0 |
Sparse fur growth | 0 | 0 | 0 | 1 |
Lung |
|
|
|
|
Collapsed areas | 0 | 0 | 0 | 0 |
Sanguineous exudate | 0 | 0 | 0 | 1 |
Petechiaeted | 0 | 0 | 0 | 2 |
Small intestine |
|
|
|
|
Catarrhal enteritis | 0 | 0 | 0 | 0 |
Liver |
|
|
|
|
Mottled | 0 | 0 | 1 | 0 |
Congested | 0 | 0 | 1 | 0 |
Kidneys |
|
|
|
|
Medullary congestion | 0 | 0 | 0 | 1 |
Cortico-medullary congestion | 0 | 0 | 1 | 1 |
Cotical grey specks | 0 | 0 | 0 | 1 |
Heart |
|
|
|
|
Apex with petechiae | 0 | 0 | 0 | 1 |
Spleen |
|
|
|
|
Congested | 0 | 0 | 0 | 0 |
Testes |
|
|
|
|
Bulged edges on section | 0 | 0 | 0 | 1 |
Females: |
|
|
|
|
Skin |
|
|
|
|
Alopecic | 0 | 0 | 0 | 1 |
Sparse fur growth | 0 | 0 | 1 | 2 |
Lung |
|
|
|
|
Collapsed areas | 0 | 0 | 0 | 1 |
Sanguineous exudate | 0 | 0 | 0 | 1 |
Petechiaeted | 0 | 0 | 0 | 0 |
Small intestine |
|
|
|
|
Catarrhal enteritis | 0 | 0 | 0 | 1 |
Liver |
|
|
|
|
Mottled | 0 | 0 | 0 | 0 |
Congested | 0 | 0 | 0 | 1 |
Kidneys |
|
|
|
|
Medullary congestion | 0 | 0 | 0 | 1 |
Cortico-medullary congestion | 0 | 0 | 0 | 0 |
Cotical grey specks | 0 | 0 | 0 | 0 |
Heart |
|
|
|
|
Apex with petechiae | 0 | 0 | 0 | 0 |
Spleen |
|
|
|
|
Congested | 0 | 0 | 0 | 1 |
Ovaries |
|
|
|
|
Dark spots | 0 | 0 | 0 | 1 |
Table 3: Subacute (21-Day) dermal toxicity study in Rabbits: Incidences of microscopic effects
Pure active ingredient cyanamide (mg/kg bw/day) | 0 | 12.5 | 25 | 37.5 |
Number of rabbits/group | 3 | 3 | 3 | 3 |
Males: |
|
|
|
|
Brain-Cerebrum |
|
|
|
|
Microcavitations (Oedema) | 0 | 0 | 1 | 2 |
Brain-Cerebellum |
|
|
|
|
Microcavitations | 0 | 0 | 0 | 1 |
Heart |
|
|
|
|
Focal Hyalinisation of Myocardial cells | 0 | 1 | 0 | 1 |
Foci of calcification | 0 | 0 | 0 | 1 |
Focal haemorrhage | 0 | 0 | 0 | 1 |
Small intestine |
|
|
|
|
Catarrh (Jejunum) | 0 | 0 | 0 | 0 |
Hyperanemia | 0 | 0 | 0 | 1 |
Kidneys |
|
|
|
|
Cysts | 0 | 0 | 0 | 0 |
Eosinophilic material in some Convoluted tubules | 0 | 1 | 0 | 3 |
Few Foci of mononuclear cells | 0 | 0 | 0 | 1 |
Liver |
|
|
|
|
Hyperaemia | 0 | 0 | 0 | 0 |
Lungs |
|
|
|
|
Focal Oedema | 0 | 0 | 0 | 2 |
Atelectasis (focal) | 0 | 0 | 0 | 0 |
Perivasular cuffing | 0 | 1 | 0 | 2 |
Testes |
|
|
|
|
Focal interstitial oedema | 0 | 0 | 0 | 1 |
Females: |
|
|
|
|
Brain-Cerebrum |
|
|
|
|
Microcavitations (Oedema) | 0 | 0 | 0 | 2 |
Brain-Cerebellum |
|
|
|
|
Microcavitations | 0 | 0 | 0 | 1 |
Heart |
|
|
|
|
Focal Hyalinisation of Myocardial cells | 0 | 0 | 0 | 0 |
Foci of calcification | 0 | 0 | 0 | 0 |
Focal haemorrhage | 0 | 0 | 0 | 0 |
Small intestine |
|
|
|
|
Catarrh (Jejunum) | 0 | 0 | 0 | 1 |
Hyperanemia | 0 | 0 | 0 | 1 |
Kidneys |
|
|
|
|
Cysts | 0 | 0 | 0 | 1 |
Eosinophilic material in some Convoluted tubules | 0 | 0 | 1 | 1 |
Few Foci of mononuclear cells | 0 | 0 | 0 | 0 |
Liver |
|
|
|
|
Hyperaemia | 0 | 1 | 1 | 1 |
Lungs |
|
|
|
|
Focal Oedema | 1 | 0 | 0 | 1 |
Atelectasis (focal) | 0 | 1 | 0 | 1 |
Perivasular cuffing | 0 | 0 | 0 | 0 |
Applicant's summary and conclusion
- Conclusions:
- The NOAEL for dermal effects in rabbits: 25 mg/kg bw
The NOAEL for systemic effects in rabbits: 25 mg/kg bw - Executive summary:
Dormex (Hydrogen cyanamide, aqueous solution) was applied undiluted to the skin of three male and three female New Zealand White rabbits per dose level for a period of six hours per day on 5 days per week for three consecutive weeks followed by a 14 day post-application observation period. The concentrations were 0, 25, 50 and 75 mg/kg bw/day equivalent to 12.5, 25 and 37.5 mg/kg bw/day active substance Cyanamide, which were selected according to the results of a pilot study. The control group did not receive any treatment of the test substance.
There were no mortalities in any groups of the test material or post-application observation period. At the highest concentration severe erythema of the skin and reduction in the fur density around the areas of application were observed. Slight erythema during the application period were observed at the mid dose of 25 mg/kg bw/day pure active substance cyanamide which recovered one day after application. There were no significant differences in the body weight and feed consumption of animals treated with Dormex when compared to the control animals. None of the haematological, clinical chemical and urine parameters of the treated groups showed any statistical significant variation as compared to the controls at each time of measurement.
After the recovery period some organ weights revealed a statistical significance in the low, mid or high dose males. However, due to the fact that there are no consistent dose-dependent changes the findings are considered to be incidental.
The gross pathological and histopathological examinations showed no consistent findings in the low and mid dose animals. Some high dose animals showed findings even after the 14 d recovery period.
Due to the irreversibility of the local skin effects at 37.5 mg/kg bw and the reversibility of the skin findings at 25 mg/kg bw the NOAEL for dermal effects is 25 mg/kg bw of ai cyanamide in rabbits. Due to the fact that there were no systemic findings in the low and mid dose animals attributable to treatment with cyanamide the NOAEL for systemic effects was deduced at the mid dose of 25 mg/kg bw based on the histopathological findings at the high dose.
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