Aluminium fluoride

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study without detailed documentation

Data source

Reference

Reference Type:

publication

Title:

Chronic administration of aluminum-fluoride or sodium-fluoride to rats in drinking water: alterations in neuronal and cerebrovascular integrity

Author:

Varner JA, Jensen KF, Horvath W, & Isaacson RL

Year:

1998

Bibliographic source:

Brain Research; 784: 284-298

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Investigating alterations in the nervous system resulting from chronic administration (i.e., 52 weeks) of aluminum fluoride.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Aluminium fluoride

EC Number:

232-051-1

EC Name:

Aluminium fluoride

Cas Number:

7784-18-1

Molecular formula:

AlF3

IUPAC Name:

aluminum trifluoride

Details on test material:

- Name of test material (as cited in study report): Aluminum fluoride

Results and discussion

Any other information on results incl. tables

General condition of the animals: Progressive general decline in appearance of the AlF3 animals noted throughout the experiment. In addition to the yellowing of the hair that occurs with age, the hair of animals in the AlF3 group became sparse revealing the underlying skin which was dry, flaky, and of a copper color. Although the body weights did not differ among the groups, there was a greater number of deaths in the AlF3 group than in the control group.

Aluminum levels in tissue samples: Brains and kidneys of the AlF3 group exhibited elevated Al levels compared to the control group. There was no difference between the groups in Al levels in the liver.

Distribution of aluminum:

• Brain: Al-fluorescence in sections of the brain was exclusively associated with vasculature where it occurred as deposits within the lumen, within endothelial cells, and in the adventitia. Greater amounts of Al-fluorescence were observed to occur in the deeper layers of the neocortex and in the hippocampus of the left hemisphere than in the right. The AlF group exhibited greater fluorescence in layers 5 and 6 of the left hemisphere than the controls. CA3 and CA4 regions of the hippocampus of the left hemisphere of the brains from the AlF3 group also exhibited increased fluorescence compared to controls.
• Kidney: Some Al-fluorescence was detected within glomeruli and tubules; however, substantially more fluorescence was associated with vasculature.
• Liver: Al-fluorescence could be detected in the sinuses and blood vessels of all animals.

Mosphological assessments:

• Kidney: Glomerular hypercellularity and mesangial proliferation apparent in animals from the AlF3 treatment groups. A deposition of protein also was noted in the tubules. There was a significant increase in the extent of monocyte infiltration in the animals treated with AlF3 compared to controls.
• Liver: No differences among the groups were observed in the liver. All hepatocytes appeared normal in shape displaying the typical rounded appearance with demonstrable nuclei and chromatin. Sinusoids, venules, and vessels all appeared normal.
• Spleen: While there was some infiltration of the marginal zones of the spleen by reactive lymphocytes in AlF3 -treated rats, no consistent pattern of treatment-related pathological alterations was apparent.
• Neuronal integrity: There were more moderately damaged and grossly abnormal cells in areas CA1 and CA4 of the right hippocampus in the AlF3 group than in the control group. In neocortical layers 2 and 3 of the left hemisphere, the AlF3 group had more abnormal cells than did controls. Corresponding increases in the frequency of normal appearing cells were observed in neocortex of control animals. In the hippocampus, neuronal density was decreased in area CA3 in the left hemisphere of the AlF3 group relative to controls. Additionally, a significant decrease in neuronal density of neocortical layers 2 and 3 was noted in the left hemisphere of AlF3 group relative to the controls. Significant reductions of cell density were found in layers 5 and 6 of the AlF3 group compared to controls in the left hemisphere.
• CerebroÍasculature integrity: In control animals, the localization of IgM was largely restricted to the vascular lumen, indicative of the integrity of the BBB to IgM. Staining of the neuronal parenchyma in the AlF3 group was significantly increased in the right hemisphere. No differences were found among the groups in the IgM immunoreactivity in the left hemisphere.