Aluminium fluoride

Toxicity to reproduction

Administrative data

Endpoint:

two-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1994

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:

1994

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)

Deviations:

not specified

GLP compliance:

no

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
- Physical state: not reported
- Analytical purity: 96%
- Lot/batch No.: not reported
- Expiration date of the lot/batch: not reported
- Storage condition of test material: not reported

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

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): ad libitum
- 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: not reported

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Details on exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): not reported
- Mixing appropriate amounts with (Type of food): not reported
- Storage temperature of food: not reported


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

Duration of treatment / exposure:

not reported

Frequency of treatment:

Daily in diet

Details on study schedule:

- F1 parental animals not mated until [...] weeks after selected from the F1 litters: not reported
- Selection of parents from F1 generation when pups were [...] days of age: not reported
- Age at mating of the mated animals in the study: [...] weeks: not reported

Doses / concentrations

Remarks:

Doses / Concentrations:
200, 600, or 1800 ppm
Basis:
nominal in diet
representing 14, 42, or 128 mg/kg bw/day for males and 16, 49, or 149 mg/kg bw/day for females, respectively, during premating.

No. of animals per sex per dose:

30 animals per group (#/sex not specified)

Control animals:

other: Yes, a dose level of 0 ppm is assumed to be a plain diet

Details on study design:

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

Positive control:

none

Examinations

Parental animals: Observations and 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: No data
- Time schedule for examinations: not reported


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

Oestrous cyclicity (parental animals):

not reported

Sperm parameters (parental animals):

not reported

Litter observations:

STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: not reported
- If yes, maximum of [...] pups/litter ([...]/sex/litter as nearly as possible); excess pups were killed and discarded: not reported


PARAMETERS EXAMINED
The following parameters were examined in [F1 / F2 / F3] offspring: not reported
[number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities, other:]


GROSS EXAMINATION OF DEAD PUPS:
yes (1800 ppm group only), for external and internal abnormalities; possible cause of death was not determined for pups born or found dead.

Postmortem examinations (parental animals):

SACRIFICE
- Male animals: not reported
- Maternal animals: not reported


GROSS NECROPSY
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.]: not reported


HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively: not reported

Postmortem examinations (offspring):

SACRIFICE
- The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at [#?] days of age: not reported
- These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows: not reported


GROSS NECROPSY
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.]: not reported


HISTOPATHOLOGY / ORGAN WEIGTHS
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively: not reported

Statistics:

not reported

Reproductive indices:

not reported

Offspring viability indices:

not reported

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

not specified

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

Details on results (P0)

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
Dental fluorosis: whitening of the upper and/or lower incisors was observed in most treated animals of both generations. Bevelled anterior edge of the lower incisor was observed in at least 67% of animals from both generations at 1800 ppm.

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
not reported

TEST SUBSTANCE INTAKE (PARENTAL ANIMALS)
not reported

REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS)
not reported

REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS)
not reported

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
not reported

ORGAN WEIGHTS (PARENTAL ANIMALS)
not reported

GROSS PATHOLOGY (PARENTAL ANIMALS)
not reported

HISTOPATHOLOGY (PARENTAL ANIMALS)
not reported

Effect levels (P0)

1

Dose descriptor:

NOEL

Remarks:

reproductive toxicity

Effect level:

600 ppm (nominal)

Sex:

male/female

Basis for effect level:

other: The NOEL is based on decreased pup body weights

Remarks on result:

other: Generation: general (not specified) (migrated information)

2

Dose descriptor:

LOEL

Effect level:

1 800 ppm (nominal)

Sex:

male/female

Basis for effect level:

other: The LOEL is based on decreased pup body weights

Remarks on result:

other: Generation: General (not specified) (migrated information)

3

Dose descriptor:

LOEL

Remarks:

systemic toxicity

Effect level:

200 ppm (nominal)

Sex:

male/female

Basis for effect level:

other: The LOEL is based on dental fluorosis

Remarks on result:

other: Generation: both parental (migrated information)

Results: F1 generation

General toxicity (F1)

Clinical signs:

not specified

Mortality / viability:

not specified

Body weight and weight changes:

effects observed, treatment-related

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

effects observed, treatment-related

Histopathological findings:

not specified

Details on results (F1)

VIABILITY (OFFSPRING)
Not reported

CLINICAL SIGNS (OFFSPRING)
Not reported

BODY WEIGHT (OFFSPRING)
significantly decreased pup body weights during lactation days 7, 14, and 21 (82%-88% of control in F1 offspring) and days 4, 7, 14, and 21 (74%-89%) of control in F2 offspring

SEXUAL MATURATION (OFFSPRING)
not reported

ORGAN WEIGHTS (OFFSPRING)
not reported

GROSS PATHOLOGY (OFFSPRING)
Pale kidneys, pale livers and enlarged hearts (@ 1800 ppm)

HISTOPATHOLOGY (OFFSPRING)
not reported

OTHER FINDINGS (OFFSPRING)
not reported

Overall reproductive toxicity

Reproductive effects observed:

not specified