… The present investigation concerns the influence of inorganic fluorine compounds on chromosomes in bone marrow and on the mytotic activity of epithelial cells of the cornea in female white rats. The animals were exposed 6 hours a day, six days a week, for 5 months, to the inhalation of cryolite (Na3AlF6) in concentrations of 3, 1, and 0.5 mg/m3 (calculated as fluoride ion), which is frequently encountered in the air of electrolysis areas of aluminum plants, and also of a mixture of 0.5 mg/m3 of cryolite and 0.35 mg/m3 of hydrogen fluoride.

Four rats were used in each variant of the experiment for cytogenic analysis. Bone marrow preparations were stained with azure-eosin. All types of chromosomal and chromatid aberrations were considered in the mataphases, but for the analysis only undamaged metaphasal plates with the typical 42 chromosomes were selected. Gaps were not included in the count of aberrations; tears were distinguished from gaps by displacement of the fragment with respect to the chromatid axis. On the average 8 metaphasal plates were analyzed for each rat. Total corneal preparations were stained with hematoxylin; mytotic activity was determined by the number of mytoses per 15,000 cells in each cornea. The experimental results were processed by dispersion analysis.

… Most of the aberrations observed were of the chromatid type. More than 70% of the damage was to individual fragments, which is typical of spontaneous mutations occurring under the influence of metabolic automutagens. Hence, in view of its marked biological activity, fluorine may be assumed to stimulate the formation of mutagenic metabolites in rats.

Although the percentage of mutations occurring int he experiments is not very large (5-6%), it is typical of inorganic mutagens. This, however, does not detract from their potential danger for humans. With long-term exposure, even weak mutagens can produce considerable damage to the practically irreversible mechanism of genetic changes. Because of the extensive industrial employment of inorganic fluorides, substantial quantities of fluorine enter the human environment and affect large numbers of people. Thus the present findings show the need for more detailed studies of the mutagenicity of fluorine in order to evaluate and predict its potential for genetic damage to man.

Other findings in this work showed that inhalation of cryolite in concentrations as low as 1 mg/m3 and also cryolite combined with HF leads to retardation effects in the central nervous system, suppression of the activity of a number of enzymes, to morphological changes in internal organs and tissues, etc. At a concentration of 0.5 mg/m3, cryolite was not observed to have these effects.

Conclusions

1. Chronic inhalation by white rats of cryolite in concentrations of 3, 1, and 0.5 mg/m3, and also of a combination of 0.5 mg/m3 of cryolite and 0.35 mg/m3 of hydrogen fluoride, had no cytostatic effect on the epithelial cells of the cornea.

2. Cryolite concentrations of 3 mg/m3 as well as a mixture of 0.5 mg/m3 of cryolite and 0.35 mg/m3 of hydrogen fluoride increases by 3 1/2 and 4 1/2 times (over controls) the percentage of cells with chromosomal aberrations in the bone marrow of rats.

3. The data indicate the need for further study of the mutagenic features of fluorine compounds in relation to their potential for harmful impact on the mechanism of inheritance in humans.