Inoculation Experiments.
—In order to control both the feeding and the inhalation experiments, and more particularly to obtain direct information of the effect of lead upon the body tissues, resource was had to the inoculation of the various lead compounds tested—namely: (1) White lead, (2) litharge, (3) lead frit. These three compounds are the three types of lead salt which are used in the Potteries, whilst white lead and litharge are the compounds causing industrial poisoning in the largest proportion of cases in other industries. As a further control, the more soluble lead salts were also made use of—namely, acetate, nitrate, and chloride—mainly for the purpose of establishing some standard of poisoning both in rate and dose.
Several rather unexpected results were derived from the inoculation experiments, which will be referred to.
The method of inoculation was to suspend the lead compound to be tested in normal saline solution or distilled water. The animal was then shaved, and the lead compound inoculated into the muscles of the back. The corrosive action of these lead salts was avoided by using a considerable quantity of diluent.
Lead frit is a constituent of low-solubility glaze—that is to say, a glaze which has not more than 5 per cent. soluble lead when subjected to the standard test of exposing 1 gramme of the glaze to a litre of 0·04 per cent. hydrochloric acid for an hour at room temperature. The frit which was the constituent of this glaze is produced by heating together litharge or lead and silica, the production being a yellow, hard, glaze-like material looking very much like sugar-candy. It is not by any means a compound of lead and silica of simple composition, as different samples show a wide variation in their lead content; whilst, in addition, the mode of its formation closely resembles that of an alloy or amalgam, and allows of the formation of a eutectic entangling in its meshes both of the constituents of which it is formed, so that a certain amount of free lead, in addition to the silicates of various descriptions, are present. At the same time the compound is highly resistant to the action of mineral acids, and, of course, much more insoluble and refractory than white lead, litharge, or other lead oxides. The body fluids, however, particularly the fluids in the subcutaneous and muscular tissue, definitely exert some action upon this fritted lead, and it was found experimentally that symptoms of poisoning could be produced in the experimental animals when even small doses were administered. A gramme of frit was inoculated, and in all but one case the animals showed definite signs of lead poisoning, and in two instances actually died with symptoms of encephalitis.
By washing the frit with distilled water, a slight diminution in the poisonousness was found, but by washing the frit with two or three changes of dilute acetic acid (3 per cent.), and then with distilled water, no pathological results followed inoculation. Water-washing frit alone definitely reduces the poisonous effect, but not to the same extent as the preliminary washing with acetic acid. On the other hand, washing with hot water had a much greater effect than cold-water washing.
Further evidence given by the inoculation experiments shows the relationship between the more soluble and the insoluble lead salts. The dose of acetate required to kill an animal was about 0·1 gramme of acetate per kilogramme body weight. On the other hand, 0·1 gramme of white lead produced no ill-effects, 0·5 gramme per kilogramme body weight produced death in about two months. In addition, those animals suffering from the more acute forms of poisoning developed definite eye changes and retinal hæmorrhages. Tortuosity and increased size of the retinal vessels were observed in several instances.
Besides controlling the experiments of feeding and inhalation, the inoculation experiments play a still more important part, as they furnish the correlation, necessarily, of the histological changes found as the result of poisoning by means of lead. In all the animals which have died of poisoning, certain definite trains of symptoms made their appearance. These symptoms were in practically all particulars similar to those observed in industrial lead poisoning in man, the onset of the affection and its clinical course corresponding to the symptom-complex in man, including those of cortical involvement, and often similar to the classical Jacksonian variety.
Throughout these experiments the animals exhibited no signs of irritation, and during the initial period, even, when loss of weight was a noticeable feature, their appetites remained exceedingly good; they were quite friendly, and purred loudly when stroked; but when symptoms of poisoning became manifest, particularly the onset of paralysis, a definite change in mental phenomena took place: the animals became quarrelsome, highly apprehensive of danger without cause, morose and lethargic by turns. At this stage, in more than one instance, acute encephalopathy supervened. The mental change was peculiarly striking in reference to Mott’s case, quoted on [p. 71], as in all respects it was exactly analogous with the train of symptoms recorded in that case. To sum up, the symptoms produced in the experimental animals by the lead compounds inoculated and respired, no matter what the particular compound of lead experimented was, were as follows:
1. Slight preliminary rise in weight at the commencement of the experiment, lasting from one to two weeks.