Zinc hexafluorosilicate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Sodium fluoride did not induce gene mutations in Salmonella typhimurium when studied with a preincubation protocol at doses of 100 to 10,000 µg/plate in strains TA98, TA100, TA1535, and TA1537; all strains were tested with Sodium Fluoride, NTP TR 393 out Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver S9 (Hawonh et aL, 1983).

 

Sodium fluoride was studied at two laboratories for induction of trifluorothymidine resistance in mouse L5178Y Iymphoma cells. In the first laboratory, sodium fluoride was positive both with and without Aroclor 1254-induced male Fischer 344 rat liver S9; the effective doses, with and without S9, ranged from 300 to 600 µg/mL (Caspary et al, 1987).

In the second laboratory, sodium fluoride was tested without S9 only, and test results were positive in the first trial at 62.5, 125, and 1,000 µg/mL and in the second trial at 800 and 900 µg/mL. The mutant colonies obtained after sodium fluoride treatment of L5178Y cells were primarily small colonies, suggesting that chromosomal abnormalities may be involved.

 

Sodium fluoride was studied for the induction of cytogenetic effects in Chinese hamster ovary (CHO) cells in two laboratories with different results. Sister chromatid exchanges (SCE) were induced in one laboratory at doses of 66.7 and 75 µg/mL without S9 and at doses greater than 1,200 µg/mL with S9. In all but one case, the positive results were seen following delayed harvest to allow cells, the division time of which was inhibited by the higher doses of sodium fluoride, to progress to the second metaphase division to the point where the cells could be scored. The laboratory reporting negative SCE results did not employ extended harvest times and was able to test up to only 50 µg/mL sodium fluoride without S9 and 500 µg/mL with S9.

 

In the tests for the induction of chromosomal aberrations (Abs), positive results were reported in one Iaboratory at doses of 400 µg/mL sodium fluoride and greater without S9. The second Iaboratory reported negative results without S9, but the highest dose tested was 200 µg/mL. Neither laboratory showed a reproducible increase in Abs in the presence of S9.

 

In summery the mechanisms by which these effects result from exposure to sodium fluoride is not known. Possibilities include

(1)disturbance of nucleotide pool balances through formation of Mg++:F nucleotide triphosphate complexes (Larsen and Klenow, 1969),

(2) alteration or inactivation of essential DNA processing enzymes through the binding of fluoride ions to cofactors such as Mg++ or ea++, and, perhaps more remotely, disruption of calcium- dependent transmembrane processes (Hughes and Barritt, 1987) or

(3) disruption of chromatin structure through hydrogen bonding analogous to that hown with uracil (aark and Taylor, 1981).

Such indirect or "secondary" effects on chromosome structure are attractive in light of the fact that there is no apparent direct mechanism for sodium fluoride to induce these effects, the reported difficulties in demonstrating reproducibility of effects, the observance of threshold doses, and the lack of clear dose-effect relationships.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (positive)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Mode of Action Analysis / Human Relevance Framework

In summery the mechanisms by which these effects result from exposure to sodium fluoride is not known. Possibilities include

(1)disturbance of nucleotide pool balances through formation of Mg++:F nucleotide triphosphate complexes (Larsen and Klenow, 1969),

(2) alteration or inactivation of essential DNA processing enzymes through the binding of fluoride ions to cofactors such as Mg++ or ea++, and, perhaps more remotely, disruption of calcium- dependent transmembrane processes (Hughes and Barritt, 1987) or

(3) disruption of chromatin structure through hydrogen bonding analogous to that hown with uracil (aark and Taylor, 1981).

Such indirect or "secondary" effects on chromosome structure are attractive in light of the fact that there is no apparent direct mechanism for sodium fluoride to induce these effects, the reported difficulties in demonstrating reproducibility of effects, the observance of threshold doses, and the lack of clear dose-effect relationships.

Justification for classification or non-classification

The substance is not classified due to the fact that there is no apparent direct mechanism for sodium fluoride to induce these effects: the reported difficulties in demonstrating reproducibility of effects, the observance

of threshold doses, and the lack of clear dose-effect relationships. For the classification the in vivo studies for Carcinogenicity are evalauted.