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EC number: 222-093-9 | CAS number: 3344-18-1
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian germ cell study: cytogenicity / chromosome aberration
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- The study was conducted according a protocol that is similar to the appropriate EU test method. It was not compliant with GLP. Some information required by the current guideline was not included in the study report. Read across to the registered substance is considered scientifically justified.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 975
- Report date:
- 1975
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EU Method B.22 (Rodent Dominant Lethal Test)
- Deviations:
- yes
- Remarks:
- no information given on determination that mating has occurred
- GLP compliance:
- no
- Type of assay:
- rodent dominant lethal assay
Test material
- Reference substance name:
- Reference substance 001
- Reference substance name:
- Citric acid
- EC Number:
- 201-069-1
- EC Name:
- Citric acid
- Cas Number:
- 77-92-9
- Molecular formula:
- C6H8O7
- IUPAC Name:
- 2-hydroxypropane-1,2,3-tricarboxylic acid
- Details on test material:
- - Name of test material (as cited in study report): Compound FDA 71-54, citric acid, granular
- Substance type: monoconstituent substance
- Physical state: solid
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Flow Laboratories random-bred, closed colony
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 325-375 g
- Assigned to test groups randomly: yes
- Fasting period before study:
- Housing: 1-5 per cage
- Diet:.ad libitum
- Water: ad libitum
- Acclimation period: 4-11 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): no information
- Humidity (%): no information
- Air changes (per hr): no information
- Photoperiod (hrs dark / hrs light): no information
IN-LIFE DATES: no information
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: physiol. saline
- Justification for choice of solvent/vehicle: none given
- Concentration of test material in vehicle: no information
- Amount of vehicle (if gavage or dermal): no information - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: no information
- Duration of treatment / exposure:
- Test 1 and test 2: 1 and 5 days
- Frequency of treatment:
- Test 1 and test 2: single dose and daily for 5 days
- Post exposure period:
- Treated male rats were mated with two virgin female rats each week for 7 (test 1) or 8 (test 2) weeks. Two weeks after mating, female rats were sacrificed and the fertility index, preimplantation loss and lethal effects were determined and compared with those same parameters from negative and positive control animals
Doses / concentrations
- Remarks:
- Doses / Concentrations:
test 1: 1.2, 12.0, 120 mg/kg bw; test 2; 300, 500, 3500 mg/kg bw
Basis:
- No. of animals per sex per dose:
- 10 male rats per dose
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- - triethylenemelamine
- Justification for choice of positive control(s): none given in report
- Route of administration: ip injection
- Doses / concentrations: 0.3 mg/kg bw
Examinations
- Tissues and cell types examined:
- The uterus was examined for corpora lutea, deciduomata (early deaths) late foetal deaths and total implantations.
- Statistics:
- Fertility index: pregnant females/mated females: treatments compared with controls using chi square, Armitage's trend for linearity;
Total number of implants: t-test, regression;
Total number of corpora lutea: t-test;
Preimplantation losses and dead implants: Freeman-Tukey transformation followed by t-test and regression;
One or more dead implants: chi-square and Armitage's trend, and probit regression analysis;
Two or more dead implants: chi-square and Armitage's trend, and probit regression analysis;
Dead implants per total implants: Freeman-Tukey arc-sine transformation.
Treatments were compared with historical controls. a nested model was used to take variations between males into account, and an analysis of weeks was provided.
Results and discussion
Test results
- Sex:
- not specified
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
Any other information on results incl. tables
In both the acute and sub-acute studies in test 1, statistically significant effects were seen in week 4.
Test 1, acute study: significant, dose related increase in average resorptions in high level dose group. Low and intermediate groups showed a less significant increase.
Test 1, subacute: significant increase in average preimplantation losses was noted at week 4 for the high level dose group.
Test 2 (carried out subsequent to test 1).
The apparent effects shown in week four in test 1 were not reproduced.
The positive control gave expected results.
Table 2 Representative results Test 1 Subacute study
Endpoint |
time from dosing of mating (week number) |
Historical control |
Negative control |
1.2 mg/kg bw |
12.0 mg/kg bw |
120 mg/kg bw |
Fertility index |
1 |
0.67 |
0.60 |
0.74 |
0.55 |
0.45 |
4 |
0.78 |
0.80 |
0.80 |
0.80 |
0.64 |
|
7 |
0.87 |
0.90 |
0.95 |
0.80 |
0.70 |
|
Preimplantation losses per female (average) |
1 |
1.5 |
1.7 |
0.9 |
0.9 |
1.6 |
4 |
0.6 |
1.3 |
1.8’ |
3.9* |
0.7 |
|
7 |
1.0 |
1.3 |
1.6 |
0.4 |
2.1 |
|
Proportions with one or more dead implants |
1 |
0.31 |
0.25 |
0 |
0.19 |
0.23 |
4 |
0.37 |
0.25 |
0.38 |
0.38 |
0.50 |
|
7 |
0.30 |
0.45 |
0.37 |
0.44 |
0.29 |
*significantly different from control, p < 0.01
‘significantly different from control, p < 0.05
Table 3 Representative results Test 2 Acute study
Endpoint |
time from dosing of mating (week number) |
Historical control |
Negative control |
500 mg/kg bw |
3500 mg/kg bw |
Positive control |
Fertility index |
1 |
0.67 |
0.80 |
0.60 |
0.50 |
0.55 |
4 |
0.84 |
0.80 |
0.80 |
0.80 |
0.55* |
|
8 |
0.83 |
0.70 |
0.80 |
0.75 |
0.70 |
|
Preimplantation losses per female (average) |
1 |
2.0 |
2.0 |
1.4 |
2.9 |
3.3’ |
4 |
1.6 |
1.4 |
1.8 |
1.8 |
6.8* |
|
8 |
2.0 |
3.1 |
1.2 |
1.8 |
1.9 |
|
Proportions with one or more dead implants |
1 |
0.28 |
0.31 |
0.333 |
0.40 |
1* |
4 |
0.40 |
0.31 |
0.50 |
0.56 |
1* |
|
8 |
0.39 |
0.29 |
0.44 |
0.27 |
0.57 |
*significantly different from control, p < 0.01
*significantly different from control, p < 0.01
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
CItric acid has been tested in a valid study according to a protocol that is similar to EU method B 22 (rodent dominant lethal assay). A statistically significant increase in resorptions was noted in a single week of the 7 (single dose) or 8 (repeated doses) studies in the first test. a repeat test showed no evidence of any effects. It is concluded that citric acid is negative for the induction of dominant lethals under the conditions of the study.
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