Lead sulphate0·046per cent.
White lead0·042
Litharge0·340

A very large number of experiments have also been performed for the purpose of determining the solubility of raw lead glaze, and white lead, in artificial digestions, the digestions having been made up in such a way that they resembled as far as possible in every particular the ordinary stomach contents. The type of digestion used was as follows:

Dry breadcrumbs140 grammes.
Hydrochloric acid5 c.c.
Lactic acid0·1 c.c.
Acetic acid0·1 c.c.
Pepsin1·2 grammes.
Milk1,200 c.c.

Digestions were performed with this mixture, and in every case the digest was divided into two portions; each portion was retained at body temperature, with agitation for a couple of hours, and at the end of that time one portion was submitted to analysis. The second portion was neutralized, sodium carbonate and pancreatic ferment added, and digestion carried on for another two and a half hours at body temperature. At the end of this time the pancreatic digest was examined.

Thirty-five digestions were performed. When 1 gramme of white lead was used—that is, 0·01 per cent., containing 0·75 per cent. of lead oxide—the quantity of lead found as lead oxide in the acid digest varied from 2 to 3 per cent., whilst the amount found in the pancreatic digest varied from 4 to 6·5 per cent. of the added salt. On increasing the amount to 12 grammes—that is, 1 per cent.—the quantity returned in the digest only increased from 1·5 to 2 per cent. In other words, in the addition of larger quantities of material the ratio of solubility did not rise in proportion to the quantity added. Where a direct pancreatic digestion was performed without the preliminary digest of the gastric contents, the amount of lead present in the digest was only about 0·2 per cent. of the quantity added; indeed, it was very much smaller than the amount dissolved out after preliminary acid digestion—that is, if the normal sequence of digestion is followed, the solubility progresses after the gastric digest has been neutralized and pancreatic ferment has been added, whereas very slow action indeed occurs as the result of action of the pancreatic digest alone. Some experiments described by Thomason[12], although carried out without special regard to the physiological question of the progressive nature of digestion, distinctly confirm the point raised. Thus, in a digest of gastric juice, milk, and bread, 5·0 per cent. of lead was dissolved, whereas when pancreatic juice alone was used only 0·4 per cent. was found to be dissolved, a remarkable confirmation of the point under discussion.

The difficulty of estimating lead present in these gastric digestions is a very real one, as, owing to the precipitation of lead by various fluids of an albuminoid nature, it is difficult to determine the amount of lead present in a given quantity of digest; moreover, in making such a digest, much of the material may become entangled among the clot of the milk in a purely mechanical fashion, and, in attempting to separate the fluid from the other portion of the digest, filtration no doubt removes any lead which has been rendered soluble first of all, and reprecipitated as an albuminate. An albuminate of lead may be formed with great ease in the following way: A 5 per cent. solution of albumin in normal saline is taken, 0·02 per cent. of hydrochloric acid is added, and 10 per cent. solution of lead chloride added as long as a precipitate is formed. The precipitate is then filtered off, and washed in a dialyser with acidulated water until no further trace of lead is found in the washings. A portion of this substance taken up in distilled water forms a solution of an opalescent nature, which readily passes through the filter and gives the reaction of protein with Millon’s reagent, and the lead reaction by means of caustic potash and sulphuretted hydrogen, but very large quantities of mineral acid are required to produce any colour with hydrogen sulphide. Lead which gains access to the stomach, either dissolved in water or swallowed as fine dust, becomes in all probability converted first into a soluble substance, chloride, acetate, or lactate, which compound is then precipitated either by the mucin present in the stomach, or by the protein constituents of the food, or by the partially digested food (peptonate of lead may be formed in the same way as the albuminate described above). In this form, or as an albuminate or other organic compound, it passes the pylorus, and becomes reprecipitated and redigested through the action of the pancreatic juice. A consideration of the action of artificial gastric juices and the properly combined experiments of gastric and pancreatic digestions suggest that the form in which lead becomes absorbed is not a chloride, but an organic compound first formed and gradually decomposed during the normal process of digestion, and absorbed in this manner from the intestine along with the ordinary constituents of food. Dixon Mann[13] has shown that about two-thirds of the lead administered by the mouth is discharged in the fæces, and that the remaining one-third is also slowly but only partially eliminated. This point is of very considerable importance in relation to industrial poisoning of presumably gastro-intestinal origin, and consideration of the experiments quoted suggests that the digestion of albuminate or peptonate may to some extent be the basis which determines the excretion of so much of the lead via the fæces. This alteration of solubility has no doubt a bearing on the immunity exhibited by many animals when fed with lead, and probably explains the fact that many of the experimental animals fed with lead over long periods exhibited no symptoms of poisoning (see [p. 85]), whereas control animals, given a far smaller quantity of lead by other means and through the lung, rapidly developed symptoms of poisoning. A diversity of opinion exists as to the effect of pepsin upon the solubility of lead. Oliver[14] considers that the pepsin has a retarding influence on the solubility of lead in the gastric juice, and Thomason’s experiments also support this view, although it is difficult to see why the action of pepsin alone should be of such extreme importance. There is also the complicating fact that other added substances in the food may mask any direct pepsin factor that may be present. Albumose and peptone rather than pepsin are to be regarded as the more important substance physiologically in their reaction with lead, and it is interesting to note that Schicksal[15] found that by exposing lead in the form of white lead in a 1 per mille solution of hydrochloric acid in the presence of peptone produced a greater solvent effect on white lead than did the diluted acid alone, and the same effect was also seen on metallic lead.

Table II.—Schicksal’s Table.

Solution.Substance.Time.Amount
dissolved
returned
as
Metallic
Lead.
(a)1·0 per cent. peptone-100 c.c.White lead, 10 grms.3 days at 37° C.0·1471grm.
0·1 per cent. HCl
(b)1·0 per cent. peptone-100 c.c.Metallic lead, 4 grms.0·0330
0·1 per cent. HCl
(c)0·1 per cent. HCl, 100 c.c. White lead, 10 grms. 0·0983
(d)0·1 per cent. HCl, 100 c.c. Metallic lead, 4 grms. 0·0194
(e)0·3 per cent. Na2CO3 Metallic lead, 4 grms. None
(f)0·3 per cent. Na2CO3 White lead
(g)0·3 per cent. Na2CO3- White lead
0·5 per cent. NaCl
(h)0·3 per cent. Na2CO3- Metallic lead
0·5 per cent. NaCl

The experiments referred to on [p. 18] undoubtedly agree with those of Schicksal. In addition to the presence of peptones, the effect of carbonic acid must be also considered, as increase in solubility in gastric and pancreatic digestions was produced when carbonic acid gas was bubbled through the digest during the period of action. The whole question of solubility of many materials in the fluids of the stomach and intestinal canal requires entire revision, not only as regards lead, but as regards a number of other metals, including arsenic.

The Mechanism of Lead Absorption.