1. Stomach, duodenum, small intestine, kidney, liver, spleen, skin, heart, aorta, lungs, brain, pancreas, adrenals, thyroid and parathyroid of rats and monkeys suffering from chronic fluorosis have been histologically examined.
2. Fluorine has not been found to have any effect on the heart muscle, aorta, skin and parathyroids, whereas it has been found to adversely affect the histological structure of the remaining tissues, though in a varying degree.
3. The pathological changes observed in these tissues have been discussed.
From the photo-micrographs given here, it can be seen that fluorine seems to cause a selective destruction of the epithelium. The epithelium has been found to be considerably damaged in the stomach, duodenum, small intestine, lungs and thyroid. The loss or damage of the epithelium of the digestive tract would undoubtedly have an adverse effect on the functions of the tract. Such a circumstance has rather already been demonstrated (Wadhwani, 1953). It has been shown that, as a result of F ingestion, the primary and secondary absorption of nitrogen, calcium and phosphorus is markedly reduced in rats, and that there is also the reduced retention of these elements in the system, or, in other words, their increased excretion in the urine, indicating either lesser utilisation of these elements at the site of the cell or their uncontrolled passage through the kidney or both. Pathological changes brought about in the kidney of the monkey’ in fluorine toxicosis would suggest that the increased urinary excretion of nitrogen, calcium and phosphorus in fluorosis, may, in part, be due to the disfunctioning of the kidney. In humans with severe chronic fluorosis. Shortt et al (1937) observed that, as judged by filtration rate and blood urea clearance values, in the majority of the cases, kidney function was impaired, and in some, markedly so. In experimental monkeys receiving 10 mgm. of NaF per kg. of body weight daily, Pandit and Rao (1940) made a similar observation, and found the presence of albumin in the urine.
Among the tissues of the circulatory system, F has not been found to have any adverse effect on the histological structure of heart muscle and aorta. The arteries, however, have been found to be thickened. Similarly, F has not been observed to affect the structure of the skin. The changes observed in the liver and spleen are of degenerative type, with fibrosis present in the case of the latter. Such a state of the liver and spleen will necessarily be reflected in the picture of the blood. It has been reported that chronic fluorine poisoning brings about a condition of anmmia. This has been shown by Leake and Ritchie (1926), and Risi (1931) in dogs, by Valjavec (1932) in rabbits, by Slagsvold (1934) in sheep, by Mazumdar and Ray (1946) in bulls, and by Shortt et al. (1937) in humans.
The effect of F on the cerebral cortex is much pronounced. There is considerable chromatolysis of the cells, and the formation of the fibrous tissue. In the final stages of chronic fluorosis, the experimental monkeys did not conduct themselves with intelligence and agility of mind normally associated with them. There was a significant lack of co-ordination in their behaviour. In humans with chronic fluorosis, Shortt et al. (1937) have made a similar observation. They found that “there was•some diminution in pain and thermal sensation in several cases; thermal sensation was lost over the lower extremities in two most severe cases; tactile and vibration sense was also lost over the same area, and, in these two cases, there was also loss of sphincter control.”
Among the ductless glands examined, F seems to have no effect on the parathyroid, and has the most deleterious effect on the adrenals, thyroid and pancreas coming next in the order. The data on the effect of F on the parathyroid have so far been conflicting (vide Introduction). It is now shown that, under normal dietetic conditions, fluorine, given in the concentration required to produce chronic fluorosis over a reasonably long period, has no effect on the parathyroid of monkeys. The administration of parathyroid hormone has not been found to arrest the development of F intoxication in growing rats (Munoz, 1936).
The effect of F on the pancreas 12) 13 has been found to be rather slight. Except for slight degeneration of the glandular and islet cells, no other change has been observed in the histological structure of pancreas of monkeys suffering from chronic fluorosis. However, Handler et al. (1946) showed that fatal F poisoning in rats was accompanied by markedly elevated blood glucose and lactic acid concentrations, and severely diminished liver and muscle glycogen concentrations, and that the administration of insulin 30 minutes before the ingestion of fluoride prevented the increase in blood glucose and decrease in muscle glycogen but did not affect the accumulation of lactic acid or the depletion of liver glycogen.
The toxic action of F on the thyroid of the monkeys has resulted in a condition similar to colloid goiter. The epithelium is considerably degenerated, and the acini are filled with a large amount of colloid which stains deeply. According to Boyd (1940), colloid goiter is a compensatory hypertrophy wherein the gland, after meeting the demands of the tissues, is unable to return to its former size. Such a condition of the thyroid has been observed in endemic goiter also, and Wilson (1941) has suggested that endemic goiter is due to F compounds present in excess in soil, diet and water, and that the distribution of endemic goiter in Punjab and England is related to the geological distribution of F, and to the distribution of human dental fluorosis.
As the suprarenal cortex controls sexual development, and the medulla stimulates all structures innervated by the sympathetic nervous system, the toxic action of F on the adrenals, causing the degeneration of the cortical cells and the medullary tissue, will have a very adverse effect on these functions of the glands.
Though F is known as a systemic poison, and F toxicosis, as a generalised systemic reaction, it cannot be said that F affects all the tissues of the system. In chronic F toxicosis, produced as a result of ingestion of small quantities over a long period, under normal dietetic conditions, F has not been found to have any effect on the heart muscle, aorta, skin and parathyroid of rats and monkeys, and its effect on the other tissues has not been observed to be equally adverse.