MATERIAL AND METHODS: Male white rats weighing about 100 grams at the start of the experiments were used in the study. They were raised in a standardized way by the Anticimex Co., Stockholm on pellets containing about 28 ppm fluoride and tap water containing about 0.1 ppm fluoride.

In a four-week pilot study 20 rats were divided in 5 groups of four animals each for the preliminary testing of two concentrations of Na2PO3F in comparison with two concentrations of NaF and one control group. Every animal was ear-marked and kept in a separate cage and as given ad libitum a diet of the following basic composition:
Skim milk powder  32.3 per cent
Potato flour  43.2 per cent
Dried yeast  8.1 per cent
Arachis oil  2.8 per cent
Cod liver oil  13.6 per cent …

RESULTS

… as shown in Table 1, the kidneys were abnormal in the majority of the animals given fluorides. Also evident in Table 1 is the fact that the kidney changes ere more severe in groups 2 and 4 than in groups 1 and 3, i.e., the highest doses gave the most severe changes…

The most obvious alteration was, as described previously, dilation of the Henle loops, most pronounced in the outer part of the medulla and the inner part of the cortex (Fig. 3). It is striking that the dilation in the four-week experiments ceased in the area where the tubule lays in close relation to the glomerulus (Fig. 4) even though no occlusions or casts were found in this part of the nephron. There was flattening of the epithelium in the dilated ducts and often it seemed to be absent [Fig. 5]. In association with this there was some infiltration of inflammatory cells in the surrounding interstitial tissue.

In the more longstanding experiments the dilation of the ducts was more severe and to some extent spread to other parts of the nephron, i.e. tubuli contorti II, tubuli contorti I and the collecting tubules…

Finally, typical granulomas were found in many areas (Figs. 8 and 9). They were always located in close relation to dilated Henle loops or dilated tubules, and after four weeks nearly all of them were seen in the medullo-cortical zone.

Eighteen of the 32 rats given fluoride for 4 weeks had typical granulomas in the kidney, and two had granuloma-like foci. The granulomas consisted of rather large, round or slightly polygonal, reticular cells, and often one or two multinucleated cells in the section. As a rule some lymphocytes and plasma cells were seen in the circumference (Fig. 10).

The number of granulomas was increasing during the experiments and greatest in the groups in which animals received the highest dosage of fluoride. Thirty two of the 43 ras surviving the fluoride dosage for 8-16 weeks showed granulomas. After 12 and 16 weeks the granulomatous lesions occasionally  occurred in the outer part of the cortex (Fig. 11)…

… In five groups the fluoride additives were, respectively: 0.17 per cent Na2PO3F, 0.34 percent Na2PO3F, 0.05 per cent Na2PO3F, 0.1 per cent NaF, no addition (control). 0.17 and 0.34 percent Na2PO3F give the same fluorine contents as 0.05 and 0.1 per cent NaF, respectively (about 226 and 454 ppm F respectively)…

Two animals out of twenty four in the 0.34 per cent Na2PO3F group and three animals out of sixteen in the 0.1 per cent NaF group died during the experiment.

… In contrast to the comparatively low acute toxicity of sodium monofluorophosphate its chronic toxicity is thus of the same order and character as that of sodium fluoride.

Note: This investigation was supported in part by Research Grant DE-01654 from the National Institute of Dental Research, National Institutes of Health, United States Public Health Service.