Aluminium fluoride

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

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

Adequacy of study:

key study

Study period:

1992

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:

1992

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 452 (Chronic Toxicity Studies)

Deviations:

not applicable

Remarks:

-no deviations were cited in the EU risk assessment

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
- Physical state: Not reported
- Analytical purity: 97.3 to 97.4%
- Lot/batch No.: Not reported
- Expiration date of the lot/batch: Not reported
- Stability under test conditions: Not reported
- Storage condition of test material: Not reported

Test animals

Species:

dog

Strain:

Beagle

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
-No other information available.

ENVIRONMENTAL CONDITIONS
-No other information available.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
-No other information available.

DIET PREPARATION
-No other information available.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

-No other information available.

Duration of treatment / exposure:

1 year

Frequency of treatment:

Daily

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 105, 387, or 1139 mg/kg bw/day (females)
Basis:
actual ingested

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0, 95, 366, 1137 mg/kg bw/day (males)
Basis:
actual ingested

Doses / concentrations 3

Remarks:

Doses / Concentrations:
0, 3000, 10000, or 30000 ppm (males and females)
Basis:
nominal in diet

No. of animals per sex per dose:

4/sex/group

Control animals:

yes, plain diet

Details on study design:

-No other information available.

Positive control:

None used.

Examinations

Observations and examinations performed and frequency:

No other information available; however, clinical signs, body weight gain, hematology, clinical chemistry, and microscopic examination were conducted.

Sacrifice and pathology:

GROSS PATHOLOGY: No data
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

effects observed, treatment-related

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not specified

Details on results:

In the animals administered 3000 ppm cryolite, slight increases in the incidence of emesis in both males and females (vomiting, white and yellow froth) were reported. Body weight gain was increased in males in the 30000 ppm dose group.

Haematology analysis revealed nucleated red cells in males receiving 3000 ppm cryolite; decreased red cell count, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, and platelets; and an increased incidence of specific alterations of red blood cell morphology (anisokaryocytes, microcytes, macrocytes, target cells, hypochromic cells, nucleated red cells, basophilic strippling, and Howell-Jolly bodies) in both males and females in the 10000 ppm dose group, and increased leukocytes (primarily segmented neutrophils and eosionphils) were observed only in females.

Based on clinical chemistry parameters, a decrease in total serum protein and calcium in males and in serum albumin in females were noted at the 10000 ppm dose group. Increased lactate dehydrogenase was determined in both males and females, and decreased blood sodium was observed in males in the 30000 ppm dose group. In females receiving 3000 ppm a decrease in specific gravity of the urine was seen. Following microscopic examination, renal lesions such as regeneration of the tubular epithelium, interstitial fibrosis, tubular dilation, interstitial infiltration with lymphocytes were observed in two males and in females administered 3000 ppm cryolite. Dilation of Bowman¿s space was reported in one male and one female receiving 10000 ppm cryolite. In addition, haematopoiesis in the liver and spleen, megakaryocytosis in the spleen, and myelofibrosis in the bone marrow were observed in males and females administered 10000 ppm cryolite.

Effect levels

1

Dose descriptor:

LOAEL

Effect level:

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

Sex:

male

Basis for effect level:

other: Increases in emesis, nucleated cells, and renal lesions

2

Dose descriptor:

LOAEL

Effect level:

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

Sex:

female

Basis for effect level:

other: Increases in emesis, renal lesions, and a decrease in urine specific gravity

Target system / organ toxicity

Critical effects observed:

not specified