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EC number: 209-143-5 | CAS number: 556-88-7
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1988
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 988
- Report date:
- 1988
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- other: LAIR: OP-STX-74
- Deviations:
- yes
- Remarks:
- The dosing phase was accomplished according to the protocol with the following exemption: Food consumption data collected on 13 September 1985 (Week 3) for animals 85D00858 through 85D00906 were lost due to a computer malfunction. Food consumption and bod
- Qualifier:
- according to guideline
- Guideline:
- other: EPA 560/6-82-001
- Deviations:
- yes
- Remarks:
- The dosing phase was accomplished according to the protocol with the following exemption: Food consumption data collected on 13 September 1985 (Week 3) for animals 85D00858 through 85D00906 were lost due to a computer malfunction. Food consumption and bod
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- GLP Compliance for LAIR study 85042
- Limit test:
- no
Test material
- Reference substance name:
- 1-nitroguanidine
- EC Number:
- 209-143-5
- EC Name:
- 1-nitroguanidine
- Cas Number:
- 556-88-7
- Molecular formula:
- CH4N4O2
- IUPAC Name:
- N-nitroguanidine
- Reference substance name:
- Sodium sulphate
- EC Number:
- 231-820-9
- EC Name:
- Sodium sulphate
- Cas Number:
- 7757-82-6
- Molecular formula:
- Na2O4S
- IUPAC Name:
- disodium sulfate
- Reference substance name:
- Sodium nitrate
- EC Number:
- 231-554-3
- EC Name:
- Sodium nitrate
- Cas Number:
- 7631-99-4
- Molecular formula:
- HNO3.Na
- IUPAC Name:
- sodium nitrate
- Reference substance name:
- 4,6-diamino-1,3,5-triazin-2(1H)-one
- EC Number:
- 211-455-1
- EC Name:
- 4,6-diamino-1,3,5-triazin-2(1H)-one
- Cas Number:
- 645-92-1
- Molecular formula:
- C3H5N5O
- IUPAC Name:
- 4,6-diamino-1,3,5-triazin-2(1H)-one
- Reference substance name:
- 6-amino-1,3,5-triazine-2,4(1H,3H)-dione
- EC Number:
- 211-456-7
- EC Name:
- 6-amino-1,3,5-triazine-2,4(1H,3H)-dione
- Cas Number:
- 645-93-2
- Molecular formula:
- C3H4N4O2
- IUPAC Name:
- 6-amino-1,3,5-triazine-2,4(1H,3H)-dione
- Test material form:
- solid: particulate/powder
Constituent 1
impurity 1
impurity 2
impurity 3
impurity 4
- Specific details on test material used for the study:
- Test substance supplier Sunflower AAP
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Bantin Kingman, Fremont, CA
- Age at study initiation: young adults
- Weight at study initiation: 95 - 264 g
- Acclimatisation period: 14 or 16 days (males and females respectively)
- Housing: clear, polycarbonate show boxes in drawner rack cageswith Alpha-dri bedding
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.3 - 27.0 °C
- Humidity (%): 31-50%
- Photoperiod (hrs dark/hrs light): 12/12 with a 0.5 hours dawn phase in and a 0.5 hours dusk phase out.
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): once a week
- Mixing appropriate amounts with (Type of food): Purina Rodent Chow 5002 Meal Form (Ralston Purina, St. Louis, MO) - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- - Chromatographic Analysis (HPLC)
All diet preparations were done in accordance with LAIR SOP OP-STX-16. All diet mixes were within 6.4% of target concentrations and were adequately homogenous. - Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- ad libitum
Doses / concentrations
- Remarks:
- Doses / Concentrations:
1.05 to 21.19 mg NiGu/g diet
Basis:
nominal in diet
- No. of animals per sex per dose:
- 15
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: basis were the results of an acute toxicity study and a 14-day subacute study. The acute oral median lethal dose exceeded a LIMIT dose of 5000 mg/kg. Thus, the upper dose level used in the subacute study was a limit dose of 1000 mg/kg. Doses were selceted on basis of a logarithmic progeresssion table.
- Rationale for animal assignment (if not random): random (weight bias, stratified animal allocation) - Positive control:
- no positive control
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study); WATER CONSUMPTION:
- Measured on a twice weekly basis
- Individual feed jars were used
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at necropsy
- Anaesthetic used for blood collection: Yes (sodium pentobarbital)
- Animals fasted: No
- How many animals: all animals
- Parameters checked in table [No.1] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at necropsy
- Animals fasted: No
- How many animals: all animals
- Parameters checked in table [No.1] were examined.
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes:
No compoud-related gross or microscopic lesions were observed. All gross and microscopic lesions were minimal to mild in severity and considered to be incidental findings commonly observed in Sprague-Dawley rats. There were no microscopic lesions that were significantly different in severity from the control using the Kolgorov-Smirnov two-tailed test.
HISTOPATHOLOGY: Yes - Statistics:
- Animal weights, food consumption, and water consumption
Equality of variances, (Levene's Test), standard one-way analysis of variance (ANOVA) / Welch one-way ANOVA, F-statistic, Kruskal-Wallis one-way ANOVA for bilirubin values,
organ weights, haematology, and serum chemistry using standard one-way ANOVA
Bartlett's test for homogeneity of groups, modified t-test / Dunnett's test
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No deaths occurred during the study.
No clinical signs of toxicity attributable to nitroguanidine administration were observed during the 90-day study period.
BODY WEIGHT AND WEIGHT GAIN
No significant differences from controls were exhibited in the male dose groups. The females in the 1000 mg/kg/day group exhibited a statistically significant (p<=0.05) decrease in the rate of growth when compared to the controls on Weeks 5, 6, 8, 9, and 12. During the course of the study, the female control group mean weight gain was 103 g while the female high-dose group mean weight gain was only 81 g.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Food consumption in the males increased in all dose groups during the 13 weeks of the study. The rate of the increase in food consumption was not dose related. Food consumption in the 1000 mg/kg/day groups was significantly (p<= 0.05) lower than in the control group during Week 1 for the males, and weeks 5 and 6 for the females.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
Water consumption by both sexes increased in a dose-related manner during the study. For the 316 and 1000 mg/kg/day groups this increased water consumption was significant.
HAEMATOLOGY
No consistent treatment-related changes were noted in serum chemistry or haematological values.
CLINICAL CHEMISTRY
No significant (p<=0.05) differences from controls were observed in electrolyte levels for either sex at any of the dose groups. The group 4 males exhibited mean cholesterol values significantly (p<=0.05) less than those of the controls of the controls at interim and terminal sacrifice, but these values remained within normal limits. The group 3 males exhibited mean LDH and total protein values significantly (p<=0.05) less than those of the controls at terminal sacrifice, but the values remained within normal limits. The group 2 and group 4 females exhibited mean triglyceride values significantly (p<=0.05) less than those of the controls at terminal sacrifice, but these values remained within normal limits.
ORGAN WEIGHTS AND RATIOS
Organ weight, organ-to-body weight ratios, and organ-to-brain weight ratios were compared for liver, spleen, adrenals, kidneys, heart, testes/ovaries, and brain. The group 3 males showed a significant (p<=0.05) decrease in absolute adrenal gland weight as compared to controls at interim sacrifice. At terminal sacrifice the males exhibited a loss in heart weight that appeared to be dose related but not statistically significant (p<=0.05). The females showed significant (p<=0.05) decreases in absolute ovarian weights in the 100, 316, and 1000 mg/kg groups at interim sacrifice, decreased brain weight at interim sacrifice in the 1000 mg/kg group and a decreased spleen weight in the 316 mg/kg group at term sacrifice. The spleen-to-brain weight ratios for the 100 and 316 mg/kg female groups were significantly (p<=0.05) decreased compared to that of the controls at terminal sacrifice.
GROSS PATHOLOGY AND HISTOPATHOLOGY: NON-NEOPLASTIC
No compound-related gross or microscopic lesions were observed. All gross and microscopic lesions were minimal to mild in severity and considered to be incidental findings commonly observed in Sprague-Dawley rats. There were no microscopic lesions that were significantly different in severity from the control using the Kolmogorov-Smirnov two-tailed test.
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: overall effects
Target system / organ toxicity
- Key result
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Nitroguanidine, fed at dose levels from 100 mg/kg/day to 1000 mg/kg/day in the diet for 90 days, did not cause any appreciable toxicological effects under the conditions of this study.
- Executive summary:
The 90-day subchronic oral toxicity of nitroguanidine was evaluated in male and female Sprague-Dawley rats. Nitroguanidine was administered in the diet at dose levels of 0, 100, 316, and 1000 mg/kg/day for 90 days. The addition of nitroguanidine to the diet consistently reduced food consumption and caused significant (p<= 0.05) increase in water consumption. Significantly (p <= 0.05) reduced weight gains were observed in the female high-dose group for 5 of the 13 weeks of the study period. No other clinical signs attributable to the test compound were observed during the study. Blood samples taken at necropsy for haematological and serum chemistry analyses exhibited no significant (p <= 0.05) abnormalities that could be attributed to nitroguanidine dosing. Microscopic examination of tissues from the control and 1000 mg/kg/day dose group animals revealed no lesions attributable to the administration of nitroguanidine. These findings indicate that nitroguanidine is nontoxic in rats when administered at doses as high as 1000 mg/kg/day for 90 days. The findings of increased water consumption suggest that nitroguanidine, which is excreted unchanged in the rat's urine, may be acting as an osmotic diuretic.
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