ÆTIOLOGY
Lead poisoning of industrial origin rarely occurs in the acute form.
Practically all cases coming under the notice of either appointed
surgeons, certifying surgeons, or even in the wards of general
hospitals, are of the subacute or chronic type. There is no reason to
suppose that lead compounds are used more frequently by the workers in
lead industries as abortifacients than by other persons.
The compounds of lead which are responsible for poisoning in industrial
processes are for the most part the hydrated carbonate, or white lead,
and the oxides of lead, whilst a comparatively small number of cases
owe their origin to compounds, such as chromates and chlorides.
The poisonous nature of any lead compound from an industrial point
of view is proportional to (1) the size of the ultimate particles
of the substance manufactured, and therefore the ease with which
such particles are capable of dissemination in the air; and (2) the
solubility of the particles in the normal fluids of the body, such as
the saliva, pharyngeal and tracheal and bronchial mucus, etc., and
the fluids of the stomach and intestine. An instance of the variation
in size of the particles of lead compounds used industrially is the
difference between ground lead silicate (fritted lead) used in the
potteries, and the size of the particles of ordinary white or “raw”
lead. By micrometric measurements one of us [K. W. G.[1]] found the
average size of the particles of fritt to be ten times that of the
white lead particles. Further, direct experiment made with equal masses
of the two compounds in such a manner that the rate of settling of the
dust arising could be directly compared in a beam of parallel light
showed presence of dust in the white lead chamber fifteen minutes
after the fritt chamber was entirely clear. It is found as a matter
of practice that where dust is especially created, and where it is
difficult to remove such dust by exhaust fans, the greatest incidence
of lead poisoning occurs. The association of dusty processes and
incidence of lead poisoning is discussed in relation to the various
trades in Chapters XV. to XVII. Fume and vapour given off from the
molten metal or compounds, such as chlorides (tinning), are only a
special case of dust.
The channels through which lead or its compounds may gain entrance to
the animal body are theoretically three in number:
1. Respiratory tract.
2. Gastro-intestinal.
3. Cutaneous.
For many years most authorities have held that industrial poisoning by
means of compounds of lead takes place directly through the alimentary
canal, and that the poison is conveyed to the mouth mainly by unwashed
hands, by food contaminated with lead dust, and by lead dust suspended
in the air becoming deposited upon the mucous membrane of the mouth and
pharynx, and then swallowed. As evidence that lead dust is swallowed,
the classical symptom of colic in lead poisoning has been adduced, on
the supposition, in the absence of any experimental proof, that the
lead swallowed acted as an irritant on the gastro-intestinal canal,
thus causing colic, and, on absorption from the canal, setting up
other general symptoms. Much of the early treatment of lead poisoning
is based upon this assumption, and the administration of sulphuric
acid lemonade and the exhibition of sulphate of magnesia and other
similar compounds as treatment is further evidence of the view that the
poisoning was considered primarily intestinal.
One of the chief objections to this view, apart from the experimental
evidence, is that in those trades where metallic lead is handled,
particularly lead rolling, very few hygienic precautions have ever
been taken in regard to washing before meals, smoking, etc. Although
in these trades the hands become coated with a lead compound (oleate),
and the workers frequently eat their food with unwashed hands, thus
affording every opportunity for the ingestion of lead, the incidence of
poisoning is by no means as high or so pronounced in these occupations
as in those giving rise to lead dust, such as the white lead industry,
where special precautions are taken, and where the incidence of
poisoning is always related to the dust breathed.
=Respiratory Tract.=--In a report on the incidence of lead poisoning
in the manufacture of paints and colours, one of us [T. M. L.[2]] in
1902 laid stress on the marked incidence of poisoning in the specially
dusty lead processes. Following on that report special attention was
given to the removal of dust by means of exhaust ventilation. With the
introduction of precautionary measures, the incidence of poisoning
underwent a marked decrease, this decrease being most definite in those
industries where efficient exhaust ventilation could be maintained
(see p. 47). Experience shows that cases of poisoning in any given
trade or manufacturing process are always referable to the operations
which cause the greatest amount of dust, and where, therefore, the
opportunity of inhaling lead dust is greatest.
The investigations of Duckering[3], referred to on p. 203, show the
amount of dust present in the air in certain dangerous processes.
His results clinch the deductions made from general observation,
that dusty processes are those especially related to incidence of
industrial poisoning. Ætiologically, therefore, the relationship of
dust-contaminated air and poisoning is undeniable, and in not a few
instances on record persons residing at a distance from a lead factory
have developed poisoning, although not employed in any occupation
involving contact with lead, aerial infection through dust remaining
the only explanation. The actual channel through which the lead dust
suspended in the air gains entrance to the body is, therefore, of
especial importance; one of two channels is open--gastro-intestinal and
respiratory.
The investigations of one of us (K. W. G.) on the experimental
production of lead poisoning in animals has shown conclusively that the
dust inhaled was far more dangerous, and produced symptoms far earlier
than did the direct ingestion of a very much larger quantity of the
same compound by way of the mouth and gastro-intestinal canal. There
is no doubt whatever that the chief agent in causing lead poisoning is
dust or fume suspended in the air. That a certain amount finds its way
into the stomach direct is not denied, but from experimental evidence
we consider the lung rather than the stomach to be the chief channel
through which absorption takes place (see p. 81).
The following table gives a specific instance of the incidence of
lead poisoning in a white lead factory, and demonstrates clearly the
ætiological importance of dust. The increase in reported cases, as well
as in symptoms of lead absorption not sufficiently severe to prevent
the individual from following his usual occupation, was associated
with the rebuilding of a portion of the factory in which the packing
of dry white lead had been carried on for a large number of years. The
alterations necessitated the removal of several floors, all of which
were thoroughly impregnated with lead dust. Before the alterations were
undertaken it was recognized that considerable danger would arise;
stringent precautions were therefore taken, and the hands engaged in
the alterations kept under special observation. Notwithstanding this
there was an increase in the number of reported cases, which were all
mild cases of colic; all recovered, and were able to return to their
work in a short time.
TABLE I.--LEAD POISONING IN A WHITE LEAD FACTORY.
The figures refer to the weekly examination of the whole of the men.
For example, if a man was returned as suffering from anæmia on three
occasions, he appears as three cases in Column 7.
+-------+-------+-------+------+------+-------+------+------+------+
| | Total | Total | Cases| Cases| | | | |
| | Number| Cases | in | in | | | | |
| | of | of | Dusty| Other| Cases | Cases| Cases| |
| | Exami-|Poison-| Pro- | Pro- |of Sus-| of | of | Blue |
| Year |nations| ing |cesses|cesses|pension|Anæmia|Tremor| Line |
+-------+-------+-------+------+------+-------+------+------+------+
| (1) | (2) | (3) | (4) | (5) | (6) | (7) | (8) | (9) |
|1905 | 5,464 | 9 | 8 | 1 | 20 | 78[B]|249[B]|311[B]|
|1906[A]| 5,096 | 18 | 16 | 2 | 9 |256 |215 |532 |
|1907 | 4,303 | 4 | 3 | 1 | 6 | 62 | 81 | 38 |
|1908 | 3,965 | 4 | 3 | 1 | 5 | 40 | 25 | 11 |
+-------+-------+-------+------+------+-------+------+------+------+
[A] Structural alterations in progress, including cutting up “lead
floor,” saturated with white lead dust.
[B] These numbers for the half-year only, the inspection being taken
over in June, 1905.
Meillère[4] goes to considerable trouble to show that absorption of
lead dust by the lung is hypothetical; that it may take place, but
that it is not a channel of absorption of practical importance. He
cites a number of opinions and experiments by various observers on the
absorption of lead through the mucous membrane of the mouth, alimentary
canal, conjunctiva, etc., and he regards the absorption of lead as one
peculiarly confined, in the majority of instances, to the intestinal
canal.
The usual view is that, in the passage of the respired dust-laden air
through the nose, the larger particles of dust are deposited first of
all upon the mucous membrane in the interior chambers of the nose;
further, a second deposit takes place on the posterior wall of the
pharynx and in the throat, where the eddies produced by the current of
air inhaled through the nostrils allow the finer particles to become
more easily deposited. Finally, should a small trace gain access to the
larynx, it is said to be deposited there upon the mucous membrane, to
be subsequently ejected, and only a very small proportion of the total
may ever find its way into the lung.
In all arduous labour, directly the respiration rate rises through
extra calls made upon the muscles of the body, an increase in the
depth of respiration takes place; yet even under these circumstances
Meillère and others incline to the view that the dust is deposited on
the mucous surfaces of the mouth and swallowed. Experimental evidence
is entirely opposed to these suppositions. In the first place, unless
particles of dust readily find their way into the lung, it is difficult
to understand how the lung itself becomes the site of so much deposit
of carbon, and of flinty material in stonegrinder’s pneumokoniosis.
The staining of the lung by means of carbon particles, particularly in
dwellers in cities, is too well known to warrant more than a passing
reference. Moreover, experimental work has shown that fine powders
suspended in the air easily reach the lung. Armit[5] has shown that
the nickel in nickel carbonyl poisoning gains direct access to the
lung, and becomes deposited there, the metallic particles being readily
demonstrated in the lung tissue itself. Further, the experiments (see
p. 84) demonstrate that white lead dust and other forms of lead dust
definitely gain access to the lung, and thus inhaled produce all the
symptoms of lead poisoning in animals subjected to the inhalation.
White lead, litharge, or red lead, are not easily suspended in water,
and long-continued mixing is necessary to make a suspension. Great
difficulty is found in “laying” lead dust by water, as the following
experiment demonstrates: Five wash-bottles are arranged in series; in
the first ground dry white lead is placed, and the other three bottles
are filled with water, and a tube laid under the surface of the water
in such a way that the air from the first bottle must pass the whole of
the water seals in each subsequent bottle. In the last bottle is dilute
nitric acid saturated with sulphuretted hydrogen. If the series is now
attached to an aspirating jar, and air drawn slowly over at the rate of
ordinary respiration, the white lead powder in the first bottle being
at the same time shaken so that the air is fully charged with finely
powdered dust, lead is quickly detected in the air passing through
the last bottle of the series, by the darkening of the solution. In
this way the presence of lead dust has been demonstrated after passing
through four 2-inch water seals and 8 feet of ¹⁄₄-inch wet rubber
tubing. Such an experiment negatives the theory that all, or even a
large quantity, of a finely divided powder becomes deposited on the
upper portion of the respiratory tract.
Particles of lead present in the air in industrial processes are
exceedingly minute, and even in ground white lead the average size
of the particle is under 1 μ. Finally, Tanquerel[6] and Stanski[7]
succeeded in producing lead poisoning experimentally by blowing lead
dust through a tube inserted in a tracheotomy opening. There remains,
therefore, no room for doubt that the lung is the pre-eminent portal
for lead absorption, particularly in industrial processes; from which
it follows, as has been extensively shown in actual practice, that
the diminution of dust in workshops and factories by means of exhaust
ventilation is invariably followed by a diminution in the number of
cases of plumbism.
=Gastro-Intestinal.=--We have dealt with absorption by way of the lung,
and have insisted that such inhalation of dust is of greater importance
in giving rise to industrial lead poisoning than gastro-intestinal
absorption. Gastro-intestinal absorption can take place, and is
by no means negligible, in ordinary industrial conditions. One of
the most interesting and important confirmatory evidences of the
absorption of lead by the gastro-intestinal canal is to be found in
the large outbreaks of poisoning in which water-supplies have been
contaminated, either at their source or locally. We have already seen
that electrolysis may play an important part in the solution of lead
in water, and also learnt from Gautier[8] that the carbon dioxide
content of water is not necessarily the sole predisposing element in
the solution of lead. In this connection an important case is described
by Thresh[9], where water by no means soft, but holding some 30 degrees
of hardness, produced lead poisoning in an isolated family. The water
in question was distinctly acid to litmus-paper, and contained a very
high percentage of nitrates; the compound or salt of lead present was
therefore one easily absorbed from the alimentary canal (see p. 86).
In all instances of water-borne lead poisoning the amount of lead
present in the water was small; but as such lead would not be
removed by boiling, the amount of water consumed per person from the
contaminated source was probably large. As the signs of poisoning
did not appear until a considerable time had elapsed, a much larger
quantity of lead was probably absorbed than would appear from the
simple statement that the water contained ¹⁄₁₀ grain per gallon.
A number of cases have been reported from use of diachylon as an
abortifacient, and the symptoms in these cases are invariably those
which occur in other severe forms of poisoning such as are met with in
industrial processes. In nearly every case colic was the first symptom,
followed later by paresis of various types--amaurosis, albuminuria,
albuminuric retinitis, melancholia, encephalopathy--and not a few of
the persons succumbed. In most of the reported cases abortion was
produced, but in some, particularly in one[10], three dozen pills
containing diachylon were taken in a month, producing acute lead
poisoning, colic, and paresis, but not abortion.
In fifteen recorded cases of the use of diachylon, fourteen showed
a lead line, in many cases distinct and broad. This point has
considerable interest, as such a line cannot have been produced by oral
contact. The drug in the form of pills would be rapidly swallowed,
and little opportunity afforded for particles to remain in the mouth.
Its presence, therefore, suggests excretion from circulating blood of
lead which has been absorbed in the intestine. The blue line will be
referred to again later (see p. 122).
Practically all cases of water poisoning and of swallowing of lead
compounds have developed colic. Further, colic is cited in all the
early recorded cases, even in the very earliest cases referred to in
the historical note, of lead poisoning; and as poisoning in those
cases had invariably taken place by swallowing the drug, it may be
presumed from this association has arisen the belief that lead must
be swallowed to produce gastro-intestinal symptoms. No attention has
been paid to the fact that a few cases of definite cutaneous absorption
of lead from the use of hair lotions have been followed by colic.
Gastro-intestinal symptoms, therefore, can be produced without the
direct ingestion of the drug, and colic is a symptom of generalized
blood-infection rather than a localized irritative action on the
intestinal mucosa. This question, again, is more related to pathology
than ætiology, and is dealt with in that section. But mention may be
made here of the fact that a number of observers, more lately Meillère,
have laid it down as an axiom that experimental production of lead
poisoning in animals gives no criterion or evidence of lead poisoning
produced in man industrially. Very grave exception must be taken at
once to such a statement. In the majority of experiments quoted by
Meillère the quantity of lead given for experimental purposes has been
large--much larger, indeed, than is necessary to produce small and
characteristic effects--and instead of chronic poisoning an acute lead
poisoning has generally been set up; and even where chronic poisoning
has supervened, the condition has as a rule been masked by the severer
initial symptoms. On the other hand, the evidence to be derived from
comparison of the various observations from animal experiments brings
out with remarkable unanimity the similarity of the symptoms to those
produced in man, and, as will be seen later in the section devoted to
Pathology, experiments by one of us (K. W. G.) have so far confirmed
this surmise; in fact, a description of a case of encephalopathy
coming on after lead poisoning of a chronic nature, described by Mott,
agrees in practically every particular with the train of symptoms as
observed in these experimental animals. Certain slight differences
as to the muscles first affected are observed, but it is practically
always the homologous muscle (the physiological action of which more
nearly resembles the human muscle) which is the one to be affected in
the animal, not the anatomical homologue. Thus, for instance, in the
cat the spinal muscles, and particularly the quadriceps extensor, is
the muscle which is first affected through the medium of the anterior
crural nerve. This extensor muscle is one which only performs a slight
amount of work in extending the knee-joint, the amount of work being,
however, disproportionate to the size of the muscle. The extensors of
the fore-feet ultimately do become weakened, but it is the hind-limb
upon which the stress first falls.
Attention has been given to the solubility of lead salts in gastric
juices, the majority of such experiments having been performed with
artificial gastric juice. The method at present in use, prescribed by
the amended rules of August, 1900, for earthenware and china factories,
is based on some, if slight, consideration of the physiology of
digestion. The method described by Rule II. states that the estimation
of the quantity of lead present in the lead fritt shall be performed as
follows:
A weighed quantity of dry material is to be continuously shaken for
one hour at room temperature with one thousand times its weight of an
aqueous solution of hydrochloric acid, containing 0·25 per cent. of
HCl. This solution is thereafter to be allowed to stand for one hour,
and to be passed through a filter. The lead salt contained in a portion
of the clear filter is then to be precipitated as lead sulphide, and
weighed as lead sulphate.
This method has been adopted on the supposition that the solubility
of a lead salt in the gastric juices is the chief source of the lead
poisoning in the Potteries, and that the hydrochloric acid content of
the solution determines, for practical purposes, the quantity of lead
dissolved out of a given sample. The temperature, however, at which
this estimation is made--namely, room temperature--is one considerably
lower than that of the body, and the quantity of lead taken up into
solution at this temperature is less than that which occurs at the
ordinary temperature of the body--37° C. Practically twice as much lead
is dissolved out of fritt at 37° C. for an hour as is rendered soluble
at the ordinary temperature of the room--about 15° C. Thomason[11], who
made some experiments in this direction, gives a figure of 2·35 lead
oxide dissolved at 15° C. and 4·54 at 37° C. In another estimation--a
matter, too, of some considerable importance--it was found that acetic
acid dissolved 1·97 per cent, at 15° C., and 3·27 at 37° C. In lactic
acid the figure was 2·28 at 15° C., and 3·53 at 37° C. It is therefore
a low estimation of the solubility of any substance by the gastric
juices if the substance is operated on at a temperature below that of
the body.
The question of the solubility of a lead salt in the gastric contents
is important in view of the small quantities of dust swallowed; and
in addition to hydrochloric acid, other substances are also present
in the gastric juice, which is by no means a simple aqueous solution
of the mineral acid. Further, the gastric juice, except in cases of
pathological type, is not acid in periods of gastric rest, unless
such acidity may be represented by the presence of fermentative
acids--acetic, lactic, and butyric.
The activity of the gastric juice on lead is directly caused by the
quantity of organic acids present in addition to the hydrochloric acid,
and by the presence of foodstuffs--(1) in the undigested and (2) in the
semidigested condition. In considering the absorption of lead products
from the gastro-intestinal canal, the normal digestive processes should
not be lost sight of--that is, the sequence of events which occur
during digestion of food. On swallowing food, no definite acidity is
present in the stomach for fifteen to twenty minutes, and even after
that time the hydrochloric acid is only commencing to be secreted. As
digestion proceeds, and the whole mass becomes partially dissolved,
such portions as are in a soluble condition are passed through the
pyloric opening at intervals, and the whole contents of the stomach do
not pass straight through the pyloric opening as through an ordinary
straight drain-pipe. As each mass of food passes onwards through the
pylorus, it comes into contact in the duodenum with pancreatic juice,
and with the bile, these alkaline fluids rapidly change the reaction,
and allow the other ferments, trypsin, etc., to become active. As the
mass proceeds onwards through the intestine, the succus entericus also
exerts its function. Finally the fluid contents of the intestine are
passed onwards through the ileo-cæcal valve. During the passage from
the pylorus to the ileo-cæcal valve, the reaction of the intestinal
contents undergoes variations, from an alkaline in the duodenum
or upper parts of the jejunum, to acid at the ileo-cæcal valve.
Practically no absorption takes place from the stomach itself; a small
quantity of water and such highly volatile fluids as alcohol may be
absorbed, but the main absorption is not commenced until the food
has left the stomach; in fact, the stomach contains no mechanism for
food absorption. The work of absorption of the products of digestion
is carried on actively through the small intestine until finally the
materials have reached the large intestine through the ileo-cæcal
valve; water is then mainly absorbed, and albuminous fluids and
substances in solution to some extent, but the amount of absorption
which takes place is infinitesimal as compared with that of the small
intestine.
These points in the physiology of digestion require to be taken
into account when discussing the absorption of lead salts in the
gastro-intestinal canal.
When human gastric juice is obtained direct from the stomach in man,
and lead is submitted to its action, definite quantities of lead pass
into solution; and, curiously enough, in the normal gastric juice lead
sulphate is as soluble as both white lead and litharge. The following
two tables give the results of the estimation of the direct action
of human gastric juice upon lead. The particular point is that the
juice was obtained by the stomach tube from persons who had been given
a simple test meal preceded by a twelve hours’ fast; the juice was
therefore in a normal condition. The tests gave the following results
in the normal stomach:
Lead sulphate 0·080 per cent.
White lead 0·048 „
Litharge 0·040 „
In the second digestion, in which the analysis of the contents
showed the patient to be suffering from the condition known as
“hyperhydrochloridia,” the results were--
Lead sulphate 0·046 per cent.
White lead 0·042 „
Litharge 0·340 „
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 breadcrumbs 140 grammes.
Hydrochloric acid 5 c.c.
Lactic acid 0·1 c.c.
Acetic acid 0·1 c.c.
Pepsin 1·2 grammes.
Milk 1,200 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.
+--------------------------------+---------------+------+-----------+
| | | | Amount |
| | | | dissolved |
| | | |returned as|
| | | | Metallic |
| Solution. | Substance. | Time.| Lead. |
+--------------------------------+---------------+------+-----------+
|(_a_) 1·0 per cent. peptone}100 |{White lead, |3 days|0·1471 grm.|
| 0·1 per cent. HCl }c.c.|{10 grms. | at | |
| | |37° C.| |
|(_b_) 1·0 per cent. peptone}100 |{Metallic lead,| „ |0·0330 „ |
| 0·1 per cent. HCl }c.c.|{4 grms. | | |
| | | | |
|(_c_) 0·1 per cent. HCl, 100 |White lead, | |0·0983 „ |
| c.c.|10 grms. | | |
| | | | |
|(_d_) 0·1 per cent. HCl, 100 |Metallic lead, | |0·0194 „ |
| c.c.|4 grms. | | |
| | | | |
|(_e_) 0·3 per cent. Na₂CO₃ |Metallic lead, | | None |
| |4 grms. | | |
| | | | |
|(_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.=--The final method of absorption
of lead particles or lead solution into the animal body remains to be
considered. Experimental phagocytosis of lead particles--as, indeed, of
any minute particles of substance--suspended in an isotonic solution,
may be observed directly under the microscope. Lead particles show no
exception to the rule, and white blood-corpuscles in a hanging-drop
preparation, made by suspending them in an isotonic salt solution and
serum, may be watched englobing particles of lead, and by appropriate
means the ingested lead may be afterwards demonstrated. In such an
experiment, much of the lead absorbed by the individual corpuscles
rapidly loses its property of giving a black precipitate with
sulphuretted hydrogen, and has apparently become converted into an
organic compound, peptonate or albuminate.
In the section devoted to the Chemistry of Lead, it has been
noted that the colloidal solutions of lead are not precipitated by
sulphuretted hydrogen, and that albuminates and peptonates of lead are
presumably of colloidal form. There seems evidence, therefore, that the
direct absorption of lead takes place by means of the phagocytes of
the body, and that in them it becomes converted into a colloidal form,
in which it is probably eliminated through the kidney and intestine,
mainly the latter.
Further evidence of the englobement of lead particles by amœbic cells
may be gained if sections of the intestines of experimental animals are
examined; in the lymphoid glands particles of lead may be seen situated
in the interior of the walls, and even in the cells. It does not by any
means follow that these particles of lead sulphide present in the cells
have been formed _in situ_; more probably the lead has been converted
into a sulphide in the intestinal lumen itself, and subsequently taken
up by the amœbic cells situated in its periphery.
Another solution is possible--namely, that the particles seen in the
intestinal wall are particles of lead in process of excretion into the
intestine itself, and that the pigmentation of the vessel walls and
cells is caused by the staining of the particles of lead passing from
the blood into the lumen of the tube, which have been converted into a
sulphide during their passage.
The localization of the staining in the large intestine, especially
in the region of the appendix in animals (cats), tends to support
this theory. The large bowel near the ileo-cæcal valve, the appendix,
and even the glands in the immediate neighbourhood, are found to
be discoloured, and to contain lead in larger quantities than any
other portion of the intestine. In extreme cases the whole of the
large intestine may be stained a greyish-blue. The bloodvessels in
the mesentery in this region are also engorged. When, however, a
salt of lead, such as lead carbonate or lead oxide, gains access to
the stomach, it may be easily converted into chloride by the free
hydrochloric acid present in the stomach; and, in addition, should
there be any chronic acid-dyspepsia (hyperchlorhydria), particularly
of the fermentative type, in which free lactic acid and other organic
acids are to be found within the viscus, small quantities of lead
swallowed as dust undergo solution and conversion into chloride or
lactate. The pouring out of acid gastric juice from the stomach glands
does not take place immediately after the first bolus of food is
swallowed, and it may be twenty minutes or half an hour before the
gastric contents have an acid reaction. During this time any lead salts
previously swallowed may become incorporated with the bolus of food and
escape absorption.
Lead in solution or suspension in the stomach which becomes mixed up
with the food, and at the same time subjected to the action of various
albuminous constituents of the food in addition to acids, causes an
albuminate or peptonate of lead to be easily formed, _and as such can
never be absorbed from the stomach direct_; practically no absorption
takes place in the stomach, and the presence of food containing
albuminate precipitates any lead in solution as an organic insoluble
salt. The bolus of food impregnated with small quantities of lead
passes onwards to the intestine, where further digestion takes place.
As the mass passes through the intestine the action gradually results
in the reappearance of acidity, but at the same time a certain quantity
of sulphuretted hydrogen is produced, some of it from the degradation
of the sulphur-containing moiety of the protein molecule by ordinary
hydrolytic process and intestinal ferments, quite apart from any
bacterial action. A portion of the lead present in the chyme may be set
free again for absorption. The bile is said to assist in the solution
of lead _in vitro_.
In experiments made by one of us, which are quoted later, it has been
shown that an isolated loop of intestine allows the absorption of a
soluble lead salt (chloride) when there is no food present in the loop.
As the food mass proceeds through the length of the intestine more and
more sulphur is set free, and an opportunity arises for the fixation of
the lead as a sulphide, but even as a sulphide it is slightly soluble.
Probably, however, most of the lead becomes absorbed long before it
reaches the stage at which free sulphur or sulphuretted hydrogen
exists for the formation of sulphide. It is highly probable that lead,
in common with a number of other heavy metals, including arsenic, is
absorbed gradually in the upper part of the intestine, and re-excreted
in the lower. Such an hypothesis is undoubtedly strongly supported by
the remarkable staining of the large intestine and the ileo-cæcal valve.
The exact mechanism of the absorption of lead from its compound with
albumin or peptone as a lead peptonate or albuminate is very difficult
to state at present; lead albuminate is undoubtedly insoluble in water
or normal saline and in albumin. The process of absorption, then,
of the metal lead from the gastro-intestinal canal is very closely
related to the absorption of other heavy metals, and the fact that
animals after very large doses of lead salts administered via the mouth
show hæmorrhages in the intestinal wall, in addition to hæmorrhages in
other parts of the body, with occasional distinct ulceration, suggests
a localized coagulative action on the vessels in the wall of the
intestine as the probable origin of the ulceration. A consideration
of this problem of lead absorption from the intestine--probably only
the minutest quantity of lead, if any, is absorbed from the stomach
direct--is one of considerable importance in the prevention of such
lead poisoning as is attributable to swallowing lead. No work in a lead
factory should be commenced in the morning without partaking of food,
because if food be present the opportunities for absorption of lead are
greatly diminished, and of all foods the one to be recommended as the
most efficient is milk, or cocoa made with milk.
The absorption of dust through the lung is probably an exceedingly
complicated reaction, and Armit’s experiments with nickel carbonyl
probably give the clue. He found that in nickel carbonyl poisoning the
volatile product was split up on the surface of the lung cells, the
metallic portion passing onwards into the lung itself, to be eventually
absorbed by the serum.
From the pathological and histological investigations described on p.
81, and from the fact that particles of lead are very readily taken
up by white blood-corpuscles, we can conclude that absorption of the
finer lead particles gaining access to the lung takes place through
the medium of these phagocyte cells, as such cells are well known to
exist within the alveoli of the lung. The stored-up carbon particles
found in the lungs in dwellers in cities show that such transference of
particles from the alveoli to the inner portions of the lung trabeculæ
is a constant phenomenon, and it is therefore easily understood how
rapidly any fine particles not of themselves irritant may be easily
taken up by the tissues. Once having gained access to the interior of
the cells, the particles subjected to the action of the serum of the
blood in the ordinary process of bathing the tissues by the exuding
lymph--nay, more, actual particles of lead--may thus be actually
transferred bodily into the finer blood-spaces, and so be carried
forward to the general circulation. Such particles as remain fixed in
the lung will undergo gradual absorption, and the constant presence of
carbonic acid in the circulating blood brought to the lung undoubtedly
largely contributes to their solution, and there is no need to
presuppose the necessity of some recondite interaction of organic acid
for the solution of the inhaled lead in the lungs.
In the absorption of the substance from the intestine, it may go direct
into the blood-stream in a similar fashion through the lacteals along
the lymph channels, and so into the thoracic duct, and finally into
the general circulation. On the other hand, a certain amount, probably
not an inconsiderable portion, is taken up by the portal circulation
and transferred direct to the liver itself. Chemical analysis of the
liver supports this view, as does also the considerable amount of
stress thrown upon the liver when poisoning has taken place from the
intestinal canal on administration of massive doses of a highly soluble
lead compound. According to Steinberg[16], excretion of lead takes
place partly from the liver by the bile. This is probable, but there
is no experimental evidence at the present time to support the view.
If such an excretion does take place, the form in which the lead is
excreted is probably one in which it is no longer soluble by digestive
action. On the other hand, it may be in so soluble a form as to become
reabsorbed from the intestine, thus setting up a constant cycle. But
such a theory is one that would require a considerable amount of
experimental evidence to support it before it could be relied on.
There is no doubt that, however absorbed, lead remains stored up in
the body in minute quantities in many places, and the close analogy
to arsenic is met with in the curious elimination of the metal by the
fæces. Cloetta[17], quoted by Dixon Mann, discovered that, although
dogs were unable to take a larger dose of arsenic than 0·0035 gramme
per day without exhibiting toxic results, they could nevertheless take
arsenic in much larger doses if it were given in the solid form, and he
was able to increase the dose to as much as 2 grammes per diem without
showing any toxic symptoms. Examination of the urine and fæces showed
that as the amount of urinary excretion of arsenic diminished, so that
in the fæces increased, and in lead poisoning, even in massive doses
swallowed in error, the amount of lead excreted by the urine rapidly
diminishes in quantity, although the patient may be still suffering
from the effects of lead poisoning. The experiments, also, quoted on
p. 100 constantly pointed to the elimination of lead by way of the
intestine, and in practically all the animals that had suffered from
chronic poisoning well-marked dark staining of the upper part of the
cæcum due to lead was invariably present. This staining and excretion
of lead of the large intestine undoubtedly takes place in man. In a
case described by Little[18], where diachylon had been administered,
the administration of a large enema containing sulphate of magnesium
came away black. A more detailed result of the experiments and a
consideration of the elimination of lead are reserved for another
chapter, but it is impossible to consider the ætiology of the disease
without some reference to the general histological channels of
absorption and excretion.
=Cutaneous Absorption of Lead.=--A considerable amount of controversy
has centred on the question of the absorption of lead through the
unbroken skin. It has been shown that such drugs as belladonna applied
to the skin alone may produce dilatation of the pupil; an ointment
containing salicylic acid spread upon the skin and thoroughly rubbed in
is followed by the appearance of derivatives of salicylic acid in the
urine; mercury may be applied to the skin, and rubbed in, in sufficient
quantities to produce salivation; and a very large number of other
drugs may be cited, all of which when applied to the unbroken epidermis
with friction produce the physiological action of the drug.
There is no reason to exclude lead from the category of drugs which may
be absorbed through the medium of the skin, and, as several observers
have shown, animals may be poisoned by lead on applying a plaster of
lead acetate to the skin. Amongst these experiments may be quoted those
of Canuet[19] and Drouet[20] on rabbits. Some observers, among whom may
be mentioned Manouvrier[21], have attempted to prove that paralysis
of the hands occurs more often in the right hand in right-handed
people, in the left hand with left-handed people, and from the various
experiments showing absorption of lead through the unbroken skin they
seek to connect the lesion of the nerve with absorption direct through
the skin of the hands.
Many objections can be urged against acceptance of this theory. Lead
workers who are constantly manipulating lead in a state of solution
with bare hands do not appear as a class to be more subject to
wrist-drop than do persons who are exposed to inhalation of fumes or
dust of lead; in fact, incidence of paralysis and of nerve lesions
generally is more severe among persons exposed to prolonged inhalation
of minute quantities of lead through the respiratory tract. The greater
the exposure to dust, the greater the number of cases of anæmia and
colic, whilst in other industries, as has already been stated, where
lead exists as an oleate on the hands of the workers day in and day
out for many years, paralysis and even colic are of rare occurrence;
in other words, persons especially exposed to the absorption of lead
through their hands show a much smaller incidence of lead poisoning of
all types than do those exposed to lead dust. Further, the pathology of
wrist-drop and similar forms of paresis tends to show that the nerve
supplying the affected muscles is not affected primarily, but that the
initial cause is hæmorrhage into the sheath of the nerve, producing
ultimate degenerative change. The hæmorrhage, however, is the primary
lesion.
REFERENCES.
[1] GOADBY, K. W.: A Note on Experimental Lead Poisoning. Journal of
Hygiene, vol. ix., No. 1, April, 1909.
[2] LEGGE, T. M.: Report on the Manufacture of Paints and Colours
containing Lead (Cd. 2466). 1905.
[3] DUCKERING, G. E.: Journal of Hygiene, vol. viii., No. 4,
September.
[4] MEILLÈRE, G.: Le Saturnisme, chap. iv. Paris, 1903.
[5] ARMIT, H. W.: Journal of Hygiene, vol. viii., No. 5, November,
1908.
[6] TANQUEREL DES PLANCHES: Traité des Maladies de Plomb, ou
Saturnines. Paris, 1839.
[7] STANSKI: _Loc. cit._
[8] GAUTIER: Intoxication Saturnine, etc. Académie de Médecine,
viii., November, 1883.
[9] THRESH, J. C.: The Lancet, p. 1033, October 7, 1905.
[10] _Ibid._, January 5, 1909.
[11] THOMASON: Report of the Departmental Committee on Lead
Manufacture: Earthenware, China, vol. ii., appendices, p. 61. 1910.
[12] _Ibid._
[13] DIXON MANN: Forensic Medicine and Toxicology, p. 495. 1908.
[14] OLIVER, SIR T.: Lead Poisoning (Goulstonian lectures). 1891.
[15] SCHICKSAL: Die Bekämpfung der Bleigefahr in der Industrie, p.
38. 1908.
[16] STEINBERG: International Congress of Industrial Hygiene.
Brussels, 1910.
[17] CLOETTA: Dixon Mann’s Forensic Medicine and Toxicology, p. 463.
[18] LITTLE: The Lancet, March 3, 1906.
[19] CANUET, T.: Thèse, Paris, 1825, No. 202. Essai sur le Plomb.
[20] DROUET: Thèse, Paris, 1875. Recherches Experimentales sur le
Rôle de l’Absorption Cutanée dans la Paralysie Saturnine.
[21] MANOUVRIER, A.: Thèse, Paris, 1873, No. 471. Intoxication par
Absorption Cutanée.