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EC number: 947-855-4 | CAS number: -
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1973
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 973
- Report date:
- 1973
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- See "Principles of method if other than guideline"
- Principles of method if other than guideline:
- Exposure started gestation day 6 (recommended start on day 5), dose level choice not justified (highest dose tested did not induce maternal effects), number of corpora lutea not determined, limited information on test substance included in report. No information on feed and environmental conditions, no analytical verification of doses, only average fetus weight males and females together per litter, no individual information on the pups, no historical control data, limited maternal toxicity parameters.
- GLP compliance:
- no
- Remarks:
- Study performed before GLP principles were implemented.
- Limit test:
- no
Test material
- Reference substance name:
- Citric acid
- EC Number:
- 201-069-1
- EC Name:
- Citric acid
- Cas Number:
- 77-92-9
- Molecular formula:
- C6H8O7
- IUPAC Name:
- citric acid
- Test material form:
- solid: crystalline
- Remarks:
- Fine white crystalline material
Constituent 1
Test animals
- Species:
- hamster
- Strain:
- other: Golden hamster
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Housing: Individually housed in mesh bottom cages
- Diet: ad libitum
- Water: fresh tap water, ad libitum
ENVIRONMENTAL CONDITIONS
- The cages were kept in temperature and humidity-controlled quarters
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- Hamsters were dosed 2 mL/kg bw (high dose) or at 1 mL/kg bw.
- Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- Females were mated with young adult males (1 to 1), and appearance of motile sperm in the vaginal smear was considered Day 0 of gestation.
- Duration of treatment / exposure:
- Five consecutive days (day 6 to day 10 of gestation).
- Frequency of treatment:
- Daily gavage.
- Duration of test:
- On gestation Day 14, all dams were sacrificed.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 2.72 mg/kg bw/day (actual dose received)
- Remarks:
- No analytical verification of exposure.
- Dose / conc.:
- 12.6 mg/kg bw/day (actual dose received)
- Remarks:
- No analytical verification of exposure.
- Dose / conc.:
- 58.7 mg/kg bw/day (actual dose received)
- Remarks:
- No analytical verification of exposure.
- Dose / conc.:
- 272 mg/kg bw/day (actual dose received)
- Remarks:
- No analytical verification of exposure.
- No. of animals per sex per dose:
- Pregnant females: 22 (negative control), 19-24 (positive control groups), 22 (groups exposed to 2.72 and 12.6 mg/kg bw/day), 23 (groups exposed to 58.7 and 272.0 mg/kg bw/day).
- Control animals:
- yes
- yes, concurrent vehicle
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
- Appearance and behaviour with particular attention to food consumption and weight.
BODY WEIGHT: Yes
- Time schedule for examinations: Gestation days 0, 8, 10, and 14
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation Day 14
- Examinations: Number of implantation sites, resorption sites, live and dead fetuses; The urogenital tract of each dam was examined in detail for anatomical abnormalities. - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
Number of implantation sites, resorption sites, live and dead fetuses - Fetal examinations:
- - Body weight (live pups)
- External examinations: Yes: All per litter
- Soft tissue examinations: Yes: One-third per litter
- Skeletal examinations: Yes: Two-third per litter
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- not specified
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- One control hamster and one high dose hamster died during the study. All other dams survived until sacrifice.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Weight increase of exposed groups was comparable to negative control group (based on average value, standard deviations not included).
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Description (incidence and severity):
- No abortions were observed.
- Pre- and post-implantation loss:
- no effects observed
- Description (incidence and severity):
- The average number of implantation sites per dam was 13.8, 13.4, 13.3, 13.2 and 13.2 for the negative control group and the groups exposed to 2.72, 12.6, 58.7 and 272.0 mg/kg bw/day, respectively. The average number of live fetuses per dam were 13.4, 13.0, 12.8, 12.7 and 12.9 for the negative control group and the groups exposed to 2.72, 12.6, 58.7 and 272.0 mg/kg bw/day, respectively. The exposure to the test substance did not have effect on implantation loss.
- Total litter losses by resorption:
- no effects observed
- Description (incidence and severity):
- All pregnant dams had live litters.
- Early or late resorptions:
- no effects observed
- Description (incidence and severity):
- The total number of resorptions was 8, 9, 5, 9 and 8 for the negative control group and the groups exposed to 2.72, 12.6, 58.7 and 272.0 mg/kg bw/day, respectively. The number of dams with one or more sites resorbed was 5, 4, 4, 6 and 6 for the negative control group and the groups exposed to 2.72, 12.6, 58.7 and 272.0 mg/kg bw/day, respectively.The percentage of dams with partial resorptions was 23.8%, 18.2%, 18.2%, 26.1% and 27.3% for the negative control group and the groups exposed to 2.72, 12.6, 58.7 and 272.0 mg/kg bw/day, respectively.
- Dead fetuses:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No dead fetuses were found in the control group. In the groups exposed to 2.72, 12.6, 58.7 and 272.0 mg/kg bw/day, 0, 7, 1 and 0 dead fetuses were found, respectively. The 7 dead fetuses were found in one nest. In absence of a dose-relationship, the dead fetuses were concidered not to be related to the test substance.
- Changes in pregnancy duration:
- not examined
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not examined - Changes in number of pregnant:
- no effects observed
- Description (incidence and severity):
- All pregnant dams that survived to term had live litters.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 272 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: No effects seen up to and including the highest dose tested.
Maternal abnormalities
- Key result
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The average fetus weight was 1.78, 1.79, 1.81, 1.78 and 1.84 g for the negative control group and the groups exposed to 2.72, 12.6, 58.7 and 272.0 mg/kg bw/day, respectively.
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not examined - Reduction in number of live offspring:
- not examined
- Changes in sex ratio:
- no effects observed
- Description (incidence and severity):
- The sex ratio (M/F) for the live fetuses was 0.74, 0.81, 0.75, 0.77 and 0.67 for the negative control group and the groups exposed to 2.72, 12.6, 58.7 and 272.0 mg/kg bw/day, respectively.
- Changes in litter size and weights:
- not examined
- Changes in postnatal survival:
- not examined
- External malformations:
- no effects observed
- Description (incidence and severity):
- No external malformations were noted in any of the groups.
- Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The number of skeletal malformations in the exposed groups did not differ from the control group (results summarized below).
- Visceral malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- At 58.7 mg/kg bw/day, one pup was found with meningoencephalocele. No other visceral malformations were found in the groups exposed to citric acid and in the negative control group. This was regarded as an incidental finding.
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 272 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No effects seen up to and including highest dose tested.
Fetal abnormalities
- Key result
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
Any other information on results incl. tables
Summary of skeletal findings (number of foetuses affected/ number of litters affected)
|
Control |
2.72 mg/kg bw/day |
12.6 mg/kg bw/day |
58.7 mg/kg bw/day |
272.0 mg/kg bw/day |
Live fetuses examined (pregnant dams) |
194 (21) |
196 (22) |
194 (22) |
203 (23) |
196 (22) |
Sternebrae |
|||||
Incomplete ossification |
95/21 |
93/21 |
66/18 |
104/22 |
72/19 |
Bipartite |
11/7 |
23/13 |
15/10 |
22/13 |
17/10 |
Extra |
1/1 |
2/2 |
8/6 |
2/2 |
1/1 |
Missing |
30/12 |
27/15 |
15/7 |
21/8 |
15/9 |
Ribs |
|||||
Incomplete ossification |
1/1 |
|
|
|
|
Fused/split |
1/1 |
|
1/1 |
|
|
Wavy |
3/3 |
|
|
|
|
Less than 12 |
2/1 |
|
|
|
|
More than 13 |
41/15 |
59/18 |
57/21 |
61/17 |
43/19 |
Vertebrae |
|||||
Incomplete ossification |
4/4 |
6/3 |
2/2 |
1/1 |
2/2 |
Skull |
|||||
Incomplete closure |
|
|
1/1 |
|
|
Extremities |
|||||
Incomplete ossification |
5/4 |
6/4 |
1/1 |
1/1 |
2/2 |
Miscellaneous |
|||||
Hyoid, missing |
4/4 |
3/2 |
1/1 |
|
1/1 |
Hyoid, reduced |
4/3 |
4/3 |
6/4 |
4/4 |
2/2 |
Applicant's summary and conclusion
- Conclusions:
- Hamsters were exposed to citric acid at 0, 2.72, 12.6, 58.7 and 272.0 mg/kg bw/day via oral gavage for 5 consecutive days during pregnancy (gestation days 6 to 10). No effects were seen in maternal animals or fetuses. The nature and number of abnormalities seen in skeletal and soft tissues of the test groups did not differ from the controls. Based on these results, it is concluded that the NOAEL (maternal and development) is at least 272.0 mg/kg bw/day in hamsters.
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