Theory Of Action

The direct irritant effects on the intestinal canal depend rather upon the oxygen - or hydrogen - compounds formed, than upon phosphorus itself, and the pain, vomiting, prostration, etc., follow from the local irritation produced, just as with other corrosive poisons.

To explain the other constitutional symptoms, and the subsequent arrest of nutrition and fatty degeneration, several modern writers have argued that the strong affinity of phosphorus for oxygen leads it to abstract that vital gas from the blood, and so induce a condition of asphyxia (Eulenburg Lecorche); but, as oxygen would be continually renewed by inspiration, and the amount that can be absorbed by the metalloid is only limited, I cannot see that such serious consequences would result; neither would asphyxia produce preliminary excitement nor subsequent waste, nor is the blood of poisoned animals always found black; it is sometimes red, a condition incompatible with asphyxia (Vigier: Bulletin, 1868). Others have argued that phosphorus indeed removes oxygen from the blood and the tissues, but with the main result of forming phosphorous and phosphoric acids, which act as local corrosive agents, and which, after absorption, destroy blood-corpuscles. The stomach contains some free oxygen, especially after food (Chevreul), and it has been suggested that, when the drug is taken under circumstances which favor its retention in the stomach and its oxidation there, then gastro-intestinal troubles are the most marked (irritant form of poisoning). That phosphoric acid is formed in the system seems proved by its excretion from the lungs; and further, it is pointed out that this acid, when injected into the veins, will destroy the corpuscles, and will lead to fatty degeneration (Personne); and although it will not act thus when given by the mouth, yet it may do so when directly generated within the system by the oxidation of free phosphorus. While allowing this to some extent, I cannot believe it possible that a sufficient amount to account for such results could be formed in this manner. Again, oxygen has proved an antidote to phosphorus-poisoning (Crocq), and turpentine acts as an antidote by a process of oxidation, while free ventilation is the best means of preventing necrosis of the maxilla, etc., in phosphorus factories (Savory, Sieveking), so that it seems at least unlikely that oxidation of phosphorus is the cause of its ill-effects.

In explaining the action of the drug I incline to accept the theory of Gubler, who suggests that it acts chiefly by the strong ozonizing power which we know burning phosphorus to possess. Although through this combustion a minimum quantity of oxygen gets lost for the respiration, the remainder would shortly acquire, from its admixture with the ozonized portion, so great an increase in combustion power as to be very likely to induce general stimulation of the system. But increased activity is accompanied by an increased waste, particularly of the blood-cells; anaemia follows this irregular activity, and fatty degeneration of the tissues and impairment in the function of the different organs take place. On the other hand, amorphous phosphorus, which has no ozonizing power, would fail to produce any such symptoms, as is really the case; but more accurate analyses of the secretions are required in order to support this hypothesis. The excretion of carbonic acid is said to be lessened (Rabuteau) -we should not expect this unless in advanced stages; as already stated, nitrogenous excretions are increased in amount, while the urinary phosphates remain about normal.

I have still to refer to the effects of Phosphuretted Hydrogen, which would readily be formed from water and phosphorus, or from any phosphides, or from the very unstable hypophosphorous acid. We have seen that this gas interferes with the digestive process, and we know that, if it be passed into defibrinated blood, it turns it black and destroys its haemoglobin (Dybkowsky); also that it possesses, equally with phosphoric acid, and other acids and substances which act destructively on the blood, the power of inducing fatty degeneration from impaired nutrition (Bence Jones and others: Medical Times, ii., 18G5, p. 593). The formation of phosphuretted hydrogen in the system would equally well explain the production of the principal toxic effects of free phosphorus, and I incline to attribute them largely to it. Lecorche states that this compound has been found in the tissues in fatal cases, and he connects its presence specially with the second or neurotic form of poisoning, in which the course is rapid and nerve-symptoms are prominent.

Fatty degeneration was found by Munk and Leyden in the tissues of frogs and rabbits within two or three days after giving phosphorus (Medical Times, ii., 1865, p. 593), and since these researches its occurrence in phosphorus-poisoning has been amply demonstrated, especially by German observers (v. Naunyn in Ziemssen's "Cyclopaedia").

In Tamassia's experiments it was very rapidly produced. He injected 3, 4, 5, 6 gr. respectively into the rectum of four animals (dogs and rabbits); toxic symptoms occurred in about fifteen minutes, death in eight hours (the temperature falling 8° F.). In all four of the animals the kidneys, and in two of them the liver also, were in a state of fatty degeneration (Medical Record, January, 1878).

Synergists

Arsenic is allied to phosphorus in its power of acting upon the blood (with advantage in small doses, in large doses with destructive effect), also in its action upon nutrition. Cantharides, oxygen, and stimulants have somewhat analogous stimulating powers. It is a curious speculation that ergot of rye owes its properties to the phosphoric acid it contains (Levi: British and Foreign Review, April, 1876).

Adjuvants are found in phosphoric acid, and in fatty and fleshy foods. Phosphoric acid has especially been shown to develop or augment the powers of phosphorus, probably from aiding in its solution and circulation (Personne). The brains of animals and the flesh of hogs are said to be rich in phosphorus, and roast food to retain more than boiled.