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EC number: 227-367-1 | CAS number: 5807-14-7
- 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
Acute Toxicity: oral
Administrative data
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 14 January 2014 to 06 February 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 014
- Report date:
- 2014
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- up-and-down procedure
- Limit test:
- no
Test material
- Reference substance name:
- 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine
- EC Number:
- 227-367-1
- EC Name:
- 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine
- Cas Number:
- 5807-14-7
- Molecular formula:
- C7H13N3
- IUPAC Name:
- 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine
- Test material form:
- solid
- Details on test material:
- - Appearance: Off-white solid
- Storage Conditions: room temperature in the dark, in a closed container under nitrogen
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Strain: Sprague-Dawley (Hsd:Sprague Dawley(TM) CD(TM))
- Age at study initiation: Eight to twelve weeks of age
- Weight at study initiation: 164 to 195 g. The body weight variation did not exceed ±20 % of the body weight of the initially dosed animal.
- Fasting period before study: Yes; animals were subjected to an overnight fast immediately before dosing and for approximately three to four hours after dosing.
- Housing: The animals were individually housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were provided with environmental enrichment items.
- Diet: ad libitum
- Water: ad libitum access to mains drinking water
- Acclimation period: At least five days
ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25 °C
- Humidity: 30 to 70 % (relative)
- Air changes: The rate of air exchange was at least fifteen changes per hour
- Photoperiod: Lighting was controlled by a time switch to give twelve hours of continuous light (06:00 to 18:00) and twelve hours of darkness.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: distilled water
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: The concentration of test material in the vehicle was 17.5, 55 and 2000 mg/mL for the 175, 500 and 2000 mg/kg dose levels, respectively.
MAXIMUM DOSE VOLUME APPLIED: The dose volume was 10 mL/kg - Doses:
- 175, 500 and 2000 mg/kg
- No. of animals per sex per dose:
- 6 females were dosed overall. The first animal was dosed at 175 mg/kg. Further animals were then treated based on the short-term results of the previously treated animal. Overall, 2 animals were dosed at 175 mg/kg, 3 animals were dosed at 550 mg/kg and 1 animal was dosed at 2000 mg/kg.
- Control animals:
- no
- Details on study design:
- - Dosing regimen: Treatment of animals was sequential (Table 1). Sufficient time (at least 48 hours) was allowed between each individual animal to confirm the outcome of the previously dosed animals.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for up to fourteen days. Individual body weights were recorded prior to dosing and seven and fourteen days after treatment or at death.
- Necropsy of survivors performed: Yes. At the end of the observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained. - Statistics:
- The oral LD50 was calculated by the maximum likelihood method. Data evaluations also included the relationship, if any, between the exposure of the animal to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, body weight changes, mortality and any other toxicological effects.
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was calculated by the statistical program.
Results and discussion
Effect levels
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 550 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- 88.94 - 2 430
- Mortality:
- The mortality data are summarised in Table 2. Two animals dosed at 550 mg/kg and the single animal dose at 2000 mg/kg died.
- Clinical signs:
- - At the 2000 mg/kg dose level, signs of systemic toxicity noted were hunched posture, ataxia, ptosis, occasional body tremors and cyanosis.
- At the 550 mg/kg dose level, signs of systemic toxicity noted in first and third treated animals were hunched posture, ataxia and laboured and noisy respiration. Additional signs of systemic toxicity noted in the third treated animal were pilo-erection, occasional body tremors, pallor of the extremities, emaciation, fasciculations and red/brown staining around the snout. Lethargy, decreased respiratory rate and ptosis were also noted in the first treated animal.
No signs of systemic toxicity were noted in the second treated animal during the observation period.
- At the 175 mg/kg dose level, no signs of systemic toxicity were noted during the observation period. - Body weight:
- Individual body weights and body weight changes are given in Table 3. Surviving animals showed expected gains in body weight over the observation period.
- Gross pathology:
- Individual necropsy findings are given in Table 4.
Abnormalities noted at necropsy of animals that died or were humanely killed during the study were dark liver, gaseous stomach, clear liquid present in the stomach and haemorrhagic gastric mucosa and non-glandular epithelium of the stomach. No abnormalities were noted at necropsy of animals that were killed at the end of the study.
Any other information on results incl. tables
Table 2: Summary of Mortality Data
Dose Level (mg/kg) |
No. of Animals that Survived |
No. of Animals that Died |
Total No. of Animals |
175 |
2 |
0 |
2 |
550 |
1 |
2 |
3 |
2000 |
0 |
1 |
1 |
All doses |
3 |
3 |
6 |
Table 3: Individual Body weights and Body Weight Changes
Dose level (mg/kg) |
Animal No. |
Body weight (g) at Day |
Body Weight (g) at Death |
Body weight Gain (g) During week |
|||
0 |
7 |
14 |
1 |
2 |
|||
175 |
1 / 1-0 |
174 |
195 |
202 |
NA |
21 |
7 |
550 |
2 / 2-0 |
176 |
- |
- |
178 |
- |
- |
175 |
3 / 3-0 |
164 |
189 |
209 |
NA |
25 |
20 |
550 |
4 / 4-0 |
195 |
206 |
217 |
NA |
11 |
11 |
2000 |
5 / 5-0 |
164 |
- |
- |
162 |
- |
- |
550 |
6 / 6-0 |
181 |
- |
- |
175 |
- |
- |
Table 4: Individual Necropsy Findings
Dose level (mg/kg) |
Animal No. |
Time of Death |
Macroscopic Observations |
175 |
1 / 1-0 |
Killed Day 14 |
No abnormalities detected |
550 |
2 / 2-0 |
Found dead Day 0 |
Liver: dark Stomach: clear liquid present Gastric mucosa: haemorrhagic Non-glandular epithelium of the stomach: haemorrhagic |
175 |
3 / 3-0 |
Killed Day 14 |
No abnormalities detected |
550 |
4 / 4-0 |
Killed Day 14 |
No abnormalities detected |
2000 |
5 / 5-0 |
Found dead Day 0 |
Gastric mucosa: haemorrhagic, severe Non-glandular epithelium of the stomach: haemorrhagic, severe |
550 |
6 / 6-0 |
Humanely killed Day 0 |
Stomach: gaseous; clear liquid present Gastric mucosa: haemorrhagic |
Applicant's summary and conclusion
- Interpretation of results:
- other: Classified as Category 4 in accordance with EU criteria
- Conclusions:
- Under the conditions of this study, the acute oral LD50 of the test material was determined to be 550 mg/kg bodyweight (95 % confidence limits 88.94 to 2430 mg/kg bodyweight). In accordance with EU criteria, the test material requires classification for Acute Toxicity as Category 4.
- Executive summary:
The study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley strain rat using the up and down procedure. It was conducted in accordance with the standardised guideline OECD 425 under GLP conditions.
A total of six female animals were dosed individually in sequence with sufficient time (at least 48 hours) between each animal, at dose levels ranging from 175 mg/kg body weight to 2000 mg/kg body weight.
The test material was administered orally by gavage as a solution in distilled water. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.
The animal treated at a dose level of 2000 mg/kg and one animal treated at a dose level of 550 mg/kg were found dead on the day of dosing. One other animal treated at a dose level of 550 mg/kg was killed in extremis four hours after dosing. There were no deaths at a dose level of 175 mg/kg.
Signs of systemic toxicity noted in the animal treated at a dose level of 2000 mg/kg were hunched posture, ataxia, ptosis, occasional body tremors and cyanosis. Signs of systemic toxicity noted at a dose level of 550 mg/kg were hunched posture, lethargy, ataxia, ptosis, pilo-erection, decreased respiratory rate, laboured and noisy respiration, occasional body tremors, pallor of the extremities, emaciation, fasciculations and red/brown staining around the snout. There were no signs of systemic toxicity noted in one animal treated at 550 mg/kg and in the animals treated at the dose level of 175 mg/kg. Surviving animals showed expected gains in body weight.
At necropsy, abnormalities noted in animals that died or were humanely killed during the study were dark liver, gaseous stomach, clear liquid present in the stomach and haemorrhagic gastric mucosa and non-glandular epithelium of the stomach. No abnormalities were noted at necropsy of animals that were killed at the end of the study.
Under the conditions of this study, the acute oral LD50 of the test material was determined to be 550 mg/kg bodyweight (95 % confidence limits 88.94 to 2430 mg/kg bodyweight). In accordance with EU criteria, the test material requires classification for Acute Toxicity as Category 4.
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