Tripotassium citrate

Developmental toxicity / teratogenicity

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

Test material information

Constituent 1

Reference substance name:

Citric acid

EC Number:

201-069-1

EC Name:

Citric acid

Cas Number:

77-92-9

IUPAC Name:

citric acid

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 or test system 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