Registration Dossier

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Documentation insufficient for assessment but available information suggests the work is probably valid. This result was obtained by valid read-across.

Data source

Reference
Reference Type:
other: summary report
Title:
Unnamed
Year:
1973

Materials and methods

GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): citric acid, FDA 71 54

Test animals

Species:
mouse
Strain:
other: Albino CD-1
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No info
- Age at study initiation: No info
- Weight at study initiation: No info
- Fasting period before study: No info
- Housing: Females singly after mating
- Diet (e.g. ad libitum): No info
- Water (e.g. ad libitum): No info
- Acclimation period: No info

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No info
- Humidity (%):No info
- Air changes (per hr): No info
- Photoperiod (hrs dark / hrs light): No info

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Yes, but no details provided
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: no info

DIET PREPARATION
- Rate of preparation of diet (frequency): No info
- Mixing appropriate amounts with (Type of food): No info
- Storage temperature of food: No info

VEHICLE
- Justification for use and choice of vehicle (if other than water): no data
- Concentration in vehicle: No info
- Amount of vehicle (if gavage): No info
- Lot/batch no. (if required): No info
- Purity: No info
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
- Impregnation procedure: no information
- M/F ratio per cage: no info
- Length of cohabitation: no info
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility. ,,NO INFO
- Further matings after two unsuccessful attempts: [NO INFO
- Verification of same strain and source of both sexes: [NO INFO
- Proof of pregnancy: [vaginal plug
- Any other deviations from standard protocol: NO INFO
Duration of treatment / exposure:
Days 6 to 15 of gestation
Frequency of treatment:
Daily, by gavage
Duration of test:
Exposure period days 0 – 15 of gestation
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 2.41, 11.2, 52.0, 241 mg/kg/bw/day
Basis:
no data
No. of animals per sex per dose:
25 females
Control animals:
yes, sham-exposed
Details on study design:
- Dose selection rationale: Not stated
- Rationale for animal assignment (if not random): Not stated

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
- Cage side observations checked in table [No.?] were included. No, but report noted that these were done on a daily basis

DETAILED CLINICAL OBSERVATIONS: Yes / No / No data
- Time schedule: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: On days 0, 6, 11,15,17

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): - NA
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: -
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: - na

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): NA
- Time schedule for examinations: YES

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day On day 17
- Organs examined: No

Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
Fetal examinations:
- External examinations: Yes
- Soft tissue examinations: Yes: [all per litter / half per litter / #? per litter ]
- Skeletal examinations: Yes: [2/3 per litter ]
- Head examinations: Yes
Statistics:
no
Indices:
no
Historical control data:
no

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
None noted

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No indication

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
> 241 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The administration of up to 241 mg/kg (body weight) of the test material to pregnant rats for 10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival . The number of abnormalities seen in either soft or ,skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated ccntrols."
Therefore the NOAEL is greater than 241 mg/kg.

Therefore the NOAEL is greater than 295 mg/kg