Aluminium fluoride

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:

key study

Study period:

1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study without detailed documentation

Data source

Reference

Reference Type:

secondary source

Title:

Unnamed

Year:

1991

Report date:

1992

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Version / remarks:

Use of guideline not reported

Deviations:

not specified

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Trisodium hexafluoroaluminate

EC Number:

237-410-6

EC Name:

Trisodium hexafluoroaluminate

Cas Number:

13775-53-6

IUPAC Name:

13775-53-6

Constituent 2

Reference substance name:

Trisodium hexafluoroaluminate

IUPAC Name:

Trisodium hexafluoroaluminate

Details on test material:

- Name of test material (as cited in study report): Cryolite
- Analytical purity: 97.3%
- Purity test date: Not reported
- Lot/batch No.: Not reported
- Expiration date of the lot/batch: Not reported
- Storage condition of test material: Not reported

Test animals

Species:

mouse

Strain:

CD-1

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Not reported
- Age at study initiation: Not reported
- Weight at study initiation: Not reported
- Fasting period before study: Not reported
- Housing: Not reported
- Diet (e.g. ad libitum): Not reported
- Water (e.g. ad libitum): Not reported
- Acclimation period: Not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported


IN-LIFE DATES: From: Not reported To: Not reported

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: aqueous methylcellulose suspension

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:


VEHICLE
- Justification for use and choice of vehicle (if other than water): Not reported
- Concentration in vehicle: Not reported
- Amount of vehicle (if gavage): Not reported
- Lot/batch no. (if required): Not reported
- Purity: Not reported

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

Not reported

Details on mating procedure:

- Impregnation procedure: Not reported
- If cohoused: Not reported
- M/F ratio per cage: Not reported
- Length of cohabitation: Not reported
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility: Not reported
- Further matings after two unsuccessful attempts: Not reported
- Verification of same strain and source of both sexes: Not reported
- Proof of pregnancy: Not reported
- Any other deviations from standard protocol: Not reported

Duration of treatment / exposure:

day 6 to day 15 of gestation

Frequency of treatment:

daily

Duration of test:

Not reported

Doses / concentrations

Remarks:

Doses / Concentrations:
30, 100, or 300 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

25

Control animals:

other: Yes, control, however, details as to whether it was sham-exposed, concurrent no treatment or concurrent vehicle only was not reported

Details on study design:

- Dose selection rationale: Not reported
- Rationale for animal assignment (if not random): Not reported
- Other: Not reported

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Not reported
- Cage side observations checked in table [No.?] were included. Not reported


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Not reported


BODY WEIGHT: Not reported
- Time schedule for examinations: Not reported



POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # Not reported
- Organs examined: Not reported


OTHER:

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Not reported
Examinations included:
- Gravid uterus weight: Not reported
- Number of corpora lutea: Not reported
- Number of implantations: Not reported
- Number of early resorptions: Not reported
- Number of late resorptions: Not reported
- Other: Not reported

Fetal examinations:

- External examinations: Not reported
- Soft tissue examinations: Not reported
- Skeletal examinations: Not reported
- Head examinations: Not reported

Statistics:

Not reported

Indices:

Not reported

Historical control data:

Not reported

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
Increased mortality at 300 mg/kg/day.
Glandular portion of stomach was red beginning at 100 mg/kg/day.
Females in the 300 mg/kg/day group exhibited dark red contents of the stomach.

Effect levels (maternal animals)

1

Dose descriptor:

NOEL

Effect level:

30 mg/kg bw/day (actual dose received)

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

LOEL

Effect level:

100 mg/kg bw/day (actual dose received)

Basis for effect level:

other: maternal toxicity

3

Dose descriptor:

NOEL

Effect level:

100 mg/kg bw/day (actual dose received)

Basis for effect level:

other: developmental toxicity

4

Dose descriptor:

LOEL

Effect level:

300 mg/kg bw/day (actual dose received)

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
Fetuses at 300 mg/kg/day exhibited bent ribs and bent limb bones

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Not reported

Applicant's summary and conclusion

Executive summary:

"RAC is of the view that the maternal mortality in the two "positive" mouse studies (this study and an additional study cited by them) is too high to allow any meaningful conclusions on developmental toxicity to be drawn from these studies (CLP Regulation, Annex I §3.7.2.4.4 "Maternal mortality greater than 10 % is considered excessive and the data for that dose level shall not normally be considered for further evaluation."). Overall, there is then no support for classification from the developmental toxicity studies".