Lead poisoning and lead absorption

by Sir Thomas Morison Legge; Kenneth Weldon Goadby

1. Slight increase of weight over the first period of poisoning, lasting from one to three weeks.

2. A progressive diminution in weight, progressing until the animal exhibited definite signs of poisoning.

3. Wasting, especially of the spinal muscles (the erector spinæ and in the lumbar region), out of proportion to the determined loss of weight; pinched facies, with frequent exhibition of running from the eyes and nose, even when not exposed to the action of lead dust, merely by inoculation.

4. Various types of paralysis, particularly in the cat; the muscles of the back and of the quadriceps extensor of the hind-legs show signs of paralysis. In the cat the quadriceps extensor is paralyzed sooner than the extensor communis digitorum in man. The cats show loss of power in the hind-limbs by inability to jump. The reflexes, particularly the knee-jerks and elbow-jerks, are first of all increased, and latterly become lost.

The chief and main sign which was noted in the histological examination of the animals inoculated was one of minute microscopical hæmorrhages (this has already been referred to); these hæmorrhages were not confined to any particular position in the body nor to any one organ. In the animals which showed symptoms of epilepsy, occasionally thickening of the pia mater was found, but invariably in such cases small hæmorrhages were found immediately under the arachnoid, not covering any great area, but apparently causing pressure upon small areas of the cortex. In others, again, the hæmorrhages were found lower down in the brain, and a few in the spinal cord. At times a large amount of hæmorrhage was to be found present at the base of the brain, spreading downwards from the medulla into the spinal canal, but this only occurred in such animals as died with encephalopathic symptoms. In animals which had signs of more chronic poisoning—that is to say, gradual loss of body weight, emaciation, constipation, contraction of the abdomen, and paresis, particularly of the hind-limbs and the muscles of the back—hæmorrhages were found in the muscles, liver, spleen, lung, heart, various positions in the abdomen, in the spinal cord, in the nerve-supply of the affected muscle, and even in the brain, none of them large enough to produce absolute destruction of more than a very minute portion of the organ in which they were situated.

Now, all these symptoms, and, more important still, the phenomena of hæmorrhage, were found in all the animals which exhibited similar symptoms, whether they were poisoned by inhalation of dusty lead compounds or fed upon lead compounds associated with alcohol; but even in some of the animals which were fed upon lead compounds—particularly white lead—and which had exhibited no definite symptoms of paralysis, or, for that matter, any symptom referable to poisoning, here and there slight histological changes which were referable to minute hæmorrhages.

The experimental work therefore carries us very considerably forward in correlating the symptomatology and pathology of lead poisoning. The symptoms produced in susceptible animals by the actual inoculation of a lead compound differ only in degree and rapidity of onset from those produced in animals submitted to inhalation with similar compounds. Feeding, on the other hand—that is, ingestion by way of the gastro-intestinal canal—even in large quantities, did not produce poisoning to any great extent, except when some material such as alcohol was added, thereby breaking down the animal’s resistance. Another interesting fact is given—that if lead is taken by the mouth in addition to milk a great deal of the poisonous effect is got rid of; thus of two animals—Nos. 46 and 47—which received lead nitrate in their food, the one in water and the other in milk, the one which received it in milk showed no effects even after four months’ experiment, whereas at the end of four months the animal which was receiving the compound in its water died. This brings out a point already insisted upon—namely, that in all lead factories it is highly important that no work should be undertaken first thing in the morning, before the workers have had a proper meal, and that in the absence of a proper meal milk is the best substitute. It is highly probable that the soluble lead salt becomes united in some form of albuminate which is dealt with later, and perhaps turned into a sulphide and excreted without absorption. There is no possible doubt, from the large series of experiments which I have performed, that lead inhaled is far more poisonous than when absorbed in any other way; further, that the amount of poisoning produced differs somewhat according to the type of compound inhaled, and the experiments, moreover, give some suggestion as to the dose which is likely to produce poisoning. It is seen, where the animal is inoculated with white lead, the dose required to produce symptoms is below 1 gramme per kilogramme of body weight, but above 0·2 gramme per kilogramme of body weight. In feeding, 0·8 gramme, and even 1 gramme, per diem for eighteen months produces no effect, although the same quantity plus an excess of alcohol rapidly produces the disease. On the other hand, as small a dose as 0·1 gramme of nitrate of lead given in water for four months produced death.

Turning to the inhalation experiments, the quantity of dust breathed when as high as 0·0007 gramme per litre produced symptoms after only twelve inhalations for a period of about thirty-seven days; whereas when the dose was reduced to 0·0001 gramme per diem the time required to produce symptoms of poisoning was 120 days; in fact, this last dose (0·0001) for the animal under experiment was almost the lower limit, as this animal showed an almost steady line of weight for a considerable time, the weight remaining up for the first hundred days, a slight variation taking place from week to week until a progressive diminution set in.

Practically all the animals poisoned manifested a very distinct diminution in body weight; in four only other symptoms of poisoning appeared first. This is a fact that is often to be noted amongst lead-workers, and if a progressive diminution in weight takes place, there is strong reason for supposing that a considerable alteration in the metabolism of the body has taken place; but it does not follow that microscopical hæmorrhages or other definite effects of poisoning are present, although such is probable.

Finally, in summing up the conclusions to be drawn from the above experiments, it has been suggested that such experiments as inoculation, experimental inhalation, or even feeding, are no criterion of the circumstances under which industrial workers become infected with lead. It is perhaps hardly necessary to refer to this point, but for the fact that it is possible this book may be made use of by those who are not in the habit of dealing with experimental pathology. One of the first and most important matters in dealing with any form of poisoning is to obtain knowledge of the actual symptoms both clinically and physiologically, as well as pathologically, of the effects of any drug, and to determine if the symptoms so produced in an experimental animal conform to the symptoms as seen in man. For the purpose, therefore, an animal is required which is susceptible to the poison, and therefore cats were used in the foregoing experiments, as it is absolutely impossible to keep a domesticated cat in any white lead works, for the animals invariably become poisoned by lead.