Besredka injected sublethal doses in rabbits, and found that the leukocytes usually contained arsenic, but not in the cases that proved fatal. He thought the leukocytes important in preventing the poisoning. Housmann (1903) found that in arsenic-habituated dogs the mucous membranes of the alimentary tract were very little penetrable. Later, Cloetta had a dog which in two years had become habituated to a daily dose of 2.6 grams of arsenic trioxide by mouth. He found that all of this but 0.13 per cent., i. e., about 1/20 grain (0.003 gm.) a day, passed out with the feces. On administering hypodermatically one-sixtieth the usual daily amount the dog died in six hours. This showed that the mucous membrane of the alimentary tract had become resistant to absorption. Joachimoglu (1916) thinks this due to an acquired resistance of the mucous membrane to injury by the arsenic. Cushny states, however, that in the arsenic-eaters a large amount of arsenic is found in the urine. A search for antibodies in these eaters has proved negative and there is no true immunity conferred. Christison was of the opinion that habit tended to increase the activity of the inorganic poisons in the blood rather than to diminish it.

Toxicology

The arsenous compounds are about twice as toxic as the arsenic. Acute poisoning is generally due to Paris-green (aceto-arsenite of copper), or white arsenic, taken with suicidal intent. The symptoms come on slowly. There is the gradual onset, in fifteen minutes to half an hour, of burning in the esophagus, pain in the abdomen, nausea, vomiting, and cramps, followed by violent diarrhea with rice-water or bloody stools, excessive thirst, suppression of the urine, prostration, and low blood-pressure from great transudation of serum. The rice-water stools are composed of serum containing rolled-up flakes of mucus and epithelial debris.

In fatal cases the patient either - (1) Grows rapidly weaker and dies in from six to twenty-four hours, or (2) after partial recovery from the acute symptoms passes slowly into a condition of collapse, with death in a few days. In the latter case the skin is said to exhale an odor of garlic (arseniuretted hydrogen). At postmortem there is fatty degeneration of liver, kidneys, heart, etc., as mentioned above, and the poison is found in nuclein combination, chiefly in the liver, but also in the other organs subject to degeneration, viz., kidneys, spleen, lungs, nervous system, blood, and the walls of the stomach and intestines. In experimental animals Dutcher and Steel found the most arsenic in muscle, liver, and kidney. Oliver reports that his dog on 1 grain of arsenic a day eventually died from chronic poisoning, but that no arsenic was found in his liver or bones.

After acute poisoning, recovery from the acute symptoms may be followed by the manifestations of chronic arsenic poisoning. In experimental work arsenous acid is given to produce acute vascular nephritis, through its effect upon the capillaries of the glomeruli. Nephritis may occur in acute or subacute poisoning in man. (See Kidneys and Suprarenals above.)

The treatment is thorough lavage of the stomach, bearing in mind that the insoluble arsenic preparations may cling closely to the inflamed stomach wall and corrode it, and so be washed off with difficulty. Freshly prepared ferric hydroxide, as in the U. S. P. preparation "ferri hydroxidum cum magnesii oxido," is the chemic antidote. It oxidizes the arsenous to an arsenic compound, and forms the iron arsenate. (See Iron.) This is not only not readily absorbable, but when absorbed is less readily ionized, and is therefore less poisonous. It must be removed by lavage. The treatment of the bowels presents difficulties, for if measures are taken to check the diarrhea, some of the arsenic may be retained in the bowel and absorbed. Probably a large dose of a saline cathartic, followed, after its elimination, by large doses of bismuth subnitrate and mucilaginous drinks or olive oil, will be best both for stomach and bowels. A hot-water bottle or atropine may relieve the abdominal cramps. Opium, bismuth, and chalk mixture may be employed, if deemed necessary, for the diarrhea, but they must not be used too early. Large doses of sodium bicarbonate are said to lessen the tendency to fatty degeneration. Further treatment is that for collapse, bearing in mind that the primary collapse is largely due to loss of fluid from the blood. A saline infusion may be of value, but transfusion promises better.

Chronic or cumulative arsenic poisoning may be produced from the gradual absorption of very minute quantities, as from the dyes in stockings and the coloring-matter of wall-paper, carpets, curtains, artificial flowers, etc. Morse reports poisoning in an infant from the blue silk lining of its basket. The famous epidemic of 1900, in which over 3000 cases of poisoning were discovered in England and Wales, occurred from minute quantities (1/7 to 2/7 of a grain of arsenic trioxide per gallon) in a cheap beer. The arsenic was traced back to the sulphuric acid which was used in the manufacture of the glucose employed in the preparation of this particular brand of beer. Starr reports that of 42 samples of furs examined in New York, 11 were heavily loaded with arsenic. Cases of poisoning are reported from the therapeutic use of the drug in chorea, pernicious anemia, etc.

The onset may be very insidious, and the stomach and bowel symptoms, though regularly present, may not be of startling character. The patients look chronically ill, and have loss of appetite, nausea, diarrhea or constipation, abdominal cramps, puffiness under the eyes, anemia, headache, irritability of temper, insomnia, debility, and emaciation. In addition there may be: (1) Swelling of the liver with or without jaundice, associated with fatty degeneration, and rarely followed by atrophy. (2) General edema. (3) Various skin eruptions. (4) A dark pigmentation of the skin, known as arsenic melanosis, with keratosis of palms and soles, falling of the hair and nails, and other trophic manifestations. (5) Peripheral neuritis, with paralysis or ataxia, pain, etc., resembling that from alcohol. (6) Cold in the head and hoarse voice.