Lead poisoning and lead absorption

by Sir Thomas Morison Legge; Kenneth Weldon Goadby

A further important fact was noticeable in animals Nos. 21 and 22 (see [p. 101]), which had been exposed to a low solubility glaze such as is used in the Potteries. Low solubility glaze is compounded with lead frit—that is to say, a lead glaze (or lead silicate) which has been finely ground. The particles of this substance are much larger than those of ordinary white lead, and in addition they are much more angular. Of three animals exposed to this glaze, one actually died of pneumonia (acute), and the other two suffered from some bronchial trouble, both of them showing distinct signs of pneumonic patches and old and chronic inflammation when examined histologically; whereas in none of the other animals exposed to white lead dust or to the high solubility glaze, which contained white lead as opposed to lead frit, no such pneumonic or fibroid changes were found. This point is of some pathological importance.

The inhalation experiments also throw some light on the quantity of lead necessary to produce poisoning. The animals in the inhalation experiments were exposed for varying periods, and constant estimations made of the lead present in the air. In a number of instances samples were taken from the cage air during the whole of the experiment, as rapidly as possible. The quantity of lead floating in the air was found to increase as the experiment progressed, although a large amount of the lead introduced was caught on the side of the cage and deposited on the floor.

In the later experiments the method of taking the samples continuously during the experiment was abandoned, and four samples only were taken, and the average recorded. A simple calculation will give the quantity of lead dust it would be possible for an animal to inhale during the whole of this period of exposure. The utmost tidal air in the case of a cat would be taken at 50 c.c. Taking the average, about 0·27 gramme of lead was inhaled during the half-hour of exposure.

Feeding Experiments.

—Twelve feeding experiments of various types are recorded. The method of experiment was as follows:

The compound under investigation was carefully weighed out each day (0·5 to 1·0 gramme), the substance being some of the same compound that was being made use of for inhalation experiments. In the case of the white lead it was found essential to mix it with the animals’ food; they were given white lead in a small amount of their food, and no further food was given for some little time after the dose of lead had been swallowed. Low and high solubility glazes were also made use of for feeding, and as a further experiment alcohol was given to the animals in addition to the previous course of lead inhalation or feeding, and the exposure to lead continued after the alcohol was given. In addition to high solubility glazes, white lead, and flue dust, a soluble salt of lead was also used, in one series the salt being the nitrate. 0·1 gramme was given daily; and it is these two nitrate animals (46 and 47) which showed distinct differences from the white lead and other feeding experiments. In one case the lead was given mixed with water, in the other mixed with milk. The animal which was fed with the nitrate dissolved in water developed encephalopathy, whereas the one in which the substance was mixed in milk exhibited no signs, though fed for a similar period. Both the animals increased in weight, which is an unusual effect in experimental lead poisoning. The question of the addition of milk, which apparently prevented the absorption of lead, is of very considerable importance, as it is highly probable, as has been pointed out with regard to the precipitation of lead by means of organic substances, that the albuminoid substances in the milk precipitate the nitrate already in a state of solution; and it may be argued from these experiments that mixing the white lead with the food would tend to prevent the lead having a toxic or deleterious effect, but even when the lead was given in the form of pills between meals no poisonous effect was noticed. Further, the quantity of white lead given was considerable, and it is highly questionable whether the quantity of lead so taken would be dissolved by the gastric juice excreted under normal circumstances in its entirety, as a very considerable quantity would pass onwards through the pylorus undissolved. Until the lead compound has become soluble it cannot react with the albuminoid constituent of the food. Ordinary dry white lead or litharge does not combine directly with albumin.

The majority of the experimental animals showed alteration in weight. The most important point which is brought out by these experiments, considering them from the point of view of inhalation, is the enormous quantity of white lead the “feeding” animals swallowed without producing any apparent symptoms. The quantities cited are the amounts given per diem, whereas in the inhalation experiments the animals were rarely exposed more than three days a week for an hour at a time (see table, [p. 101]). The quantity of lead, therefore, given by the gastro-intestinal canal was at least ten times as much, in many cases fifteen or twenty times as much, as could be taken by the other animals via the lung during inhalation, and yet these animals showed little or no susceptibility to poisoning when fed with white lead or other lead compounds, unless alcohol was given in addition.

An examination of the stomach after death showed, in the case of the alcoholic animals, distinct evidence of gastritis, and there is some reason to suppose that in such animals a degree of hyperacidity may have existed, thereby promoting the rate of solution of the lead.

The increased susceptibility to lead poisoning through the agency of alcohol is interesting. No. 6 received, in addition to its inhalations or period of exposure in the dusty air, 50 c.c. of port wine per diem. Symptoms of lead poisoning appeared a day sooner than in any other animal, and if we eliminate this experiment, as the dust (flue dust from blast-furnace) contained also arsenic and antimony, three days sooner than the litharge animal, and twenty-five days sooner than the other animals exposed to white lead dust. In addition, this animal was the only one which actually died during the period of experiment; all the other animals were killed at the end of two months and submitted to histological examination; but the animal which had received alcohol died with symptoms closely simulating lead encephalopathy in man. The predisposing action of alcohol is still further emphasized by the subsequent experiments with three animals exposed to white lead dust; one was exposed thirty-seven and the other thirty days before symptoms appeared, whereas when alcohol was given poisoning was apparent within twelve days, and after only four inhalations.

In the case of animals fed with white lead, one after eight months, and the other a year and a half, showed no signs of lead poisoning at all, while the weights remained constant. At the end of this time alcohol (50 c.c. of port wine) was added to the animals’ diet, and one month after the addition of alcohol to the diet, the dose of white lead being continued constant, encephalopathy ensued. In a second case the animal was started on alcohol in addition to the white lead. In a month it was showing signs of slight paresis. Again, an animal fed on a low-solubility frit consisting of ground-up lead silicate, showed no ill-effects after receiving a daily dose of this compound. At the end of this time alcohol was added to its diet, and six months later the animal developed symptoms of cerebral involvement, which continued at intervals until a fatal attack of encephalopathy at the end of a year. There is thus definite evidence to show that the addition of alcohol to the animal’s diet undoubtedly hastened and determined the appearance of lead poisoning, and this, taken in conjunction with the inhalation experiments previously cited, is very strong evidence of the increased susceptibility to lead poisoning produced by alcohol. This supersensitiveness to lead through the medium of alcohol is a matter of clinical experience to most persons who have had experience of industrial lead poisoning, particularly those who have been engaged in the routine examination of persons working in factories.