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EC number: 200-556-6 | CAS number: 63-37-6
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1995
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 995
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Principles of method if other than guideline:
- - Principle of test: To provide general information concerning the effects of prenatal exposure on the pregnant test animal and on the developing organism.
- Short description of test conditions: Albino rabbits were administered orally at a dose of 800 mg/kg during the organogenesis phase (from 7th to 18th day of gestation). On day 29th, the animals were sacrificed and mothers and foetuses were examined.
- Parameters analysed / observed: Any signs of both maternotoxicity or embryotoxicity. - GLP compliance:
- not specified
- Limit test:
- yes
Test material
- Reference substance name:
- Citicoline
- EC Number:
- 213-580-7
- EC Name:
- Citicoline
- Cas Number:
- 987-78-0
- Molecular formula:
- C14H26N4O11P2
- IUPAC Name:
- (2-{[({[(2R, 3S, 4R, 5R)-5-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl] methyl phosphonato}oxy)(hydroxy)phosphoryl]oxy}ethyl)trimethylazanium
- Details on test material:
- Synonym: CDP-Choline
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- not specified
- Details on test animals or test system and environmental conditions:
- Albino rabbits.
Administration / exposure
- Route of administration:
- not specified
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- From 7th to 18th day of gestation
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 800 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- Not reported
- Control animals:
- yes, concurrent vehicle
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: No data
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 29, and the foetuses were removed for examination.
- Organs examined: No data
- Fetal examinations:
- Foetuses were removed for examination.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No toxicity signs were observed on maternal animals.
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- no mortality observed
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not specified
Maternal developmental toxicity
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- not specified
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- not specified
- Changes in number of pregnant:
- not specified
- Other effects:
- not specified
- Details on maternal toxic effects:
- No signs of maternal toxicity were observed.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 800 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- dead fetuses
- gross pathology
- mortality
- necropsy findings
Maternal abnormalities
- Key result
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- not specified
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- A slight delay in cranial osteogenesis was observed in 10% of treated fetuses.
- Details on embryotoxic / teratogenic effects:
- No signs of embriofoetal toxicity were observed.
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 800 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- reduction in number of live offspring
- external malformations
- skeletal malformations
Fetal abnormalities
- Key result
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- Citicoline at 800 mg/kg bw did not exhibit neither maternal or foetal toxicity in rabbits. Therefore, the NOAEL for both maternal and developmental toxicity in rabbits is 800 mg/kg bw.
- Executive summary:
A study was conducted to assess the potential teratogenic effects of citicoline. Albino rabbits were administered 0 (control) or 800 mg citicoline/kg bw per day on gestation days 7 to 18. The animals were killed on gestation day 29, and the foetuses were removed for examination. No signs of maternal or foetal toxicity were reported. Approximately 10% of the foetuses exposed to citicoline were reported to display a slight delay in cranial osteogenesis. However, this difference was not considered by the authors to represent an adverse effect of citicoline on organogenesis. Therefore, the NOAEL for both maternal and developmental toxicity in rabbits is 800 mg/kg bw.
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