Chapter XXXII

THE EFFECTS OF DINITROBENZINE AND OTHER NITRO-SUBSTITUTION
PRODUCTS OF THE AROMATIC SERIES ON THE WORKMEN EMPLOYED IN THE
MANUFACTURE OF HIGH EXPLOSIVES.

There are about fourteen authorised explosives in use in the United Kingdom, all of which contain, more or less, naphthalene and the aromatic nuclei, benzine, toluene, either singly or combined. These nuclei, when nitrated, form the usual combustible elements in high explosives.

The dinitro compounds of benzine exist in three varieties, ortho, meta, and para. The ordinary commercial form consists almost entirely of metadinitrobenzine, and is generally used in the manufacture of high explosives. This is in some cases mixed with a chlorinated hydrocarbon. The metadinitrobenzine is usually commercially pure, it rarely contains a trace of mononitrobenzine, or the lower oxides of nitrogen. A little free acid is generally found which colours the crystals yellow, and stains the hands of the workmen. It is very sensibly volatile at a temperature of 48° C. At ordinary temperatures it is solid, as are also its isomerides, para and orthonitrobenzine.

The proportions used in the various explosives differ very largely, ranging from 5 to 20 per cent. in the finished explosives. In a smaller number the mono, di, and tri nitrobenzine, toluene, and naphthalene are employed either alone or in combination.

When comparing the poisonous nature of these substances, naphthalene is probably not poisonous, whilst some of the toluene compounds are more poisonous than the benzine.

There is evidence that, generally speaking, the higher the nitration of the aromatic series, the more dangerous these substances are to manipulate.

This is borne out by the following investigations, which we communicated to the _Lancet_, August 31, 1901:--

“We found that mononitrobenzine when given by the mouth to cats was quite harmless, they seemed rather to thrive and grow fat upon it. Dinitrobenzine is exceedingly poisonous both to men and animals. 1.2 grammes given to a cat by the mouth proved fatal in about three hours. The smallest lethal dose for a cat of 6 lb. in weight, given by the mouth in one dose, was .08 gramme. In another instance .06 gramme given in the same manner was almost fatal. A lethal dose of .09 gramme of dinitrobenzine, when given over a consecutive number of days in divided doses of .04, .02, .01, and .02 gramme, did not cause death.”

“Hypodermically, .04 gramme did not prove fatal to a cat.

“In experimenting upon animals with trinitrobenzine, we found that it was distinctly but not much more poisonous than dinitrobenzine.

“Coming to the toluene group, the administration of mononitrotoluene proved, like its homologue mononitrobenzine, quite inert.

“There is great difference of opinion amongst manufacturers as to whether dinitrotoluene has lethal properties or not. The weight of evidence rather supports the latter view. We are investigating this point (_Lancet_, August 31, 1901).

“Trinitrotoluene is not poisonous under ordinary use.

“For comparative purposes we injected 50 minims of a 1 per cent. solution of dinitrobenzine into a cat, with a fatal result. We then injected 60 minims of a 1 per cent. solution of trinitrotoluene into another cat, with the result that the only effect appeared to be some slight cyanosis.

“Again, 90 minims of a 1 per cent. solution of dinitrobenzine given hypodermically was quickly fatal to a cat, whilst 90 minims of a 1 per cent. trinitrotoluene proved perfectly innocuous.”

This is a very important practical point, as the susceptibility of man and animals seems closely allied. In some factories the trinitrotoluene has been substituted for dinitrobenzine, with great advantage to the health of the workmen employed.

The oxidising bodies used are the nitrates of ammonium, potassium, and barium. These do not appear to affect the workmen injuriously.

The gases produced by the complete detonation of these high explosives, when well diluted with air, are for all practical purposes harmless.

During the process of the manufacture of these high explosives an intimate mixture of the organic compound with the oxidising body results. This is effected in the case of chlorinated metadinitrobenzine (of which this article chiefly treats), by the processes of grinding, melting at a temperature of 98.9° C., cooling, mixing in a closed, heated, jacketed pan at a temperature of 80° C., and finally filling in air-tight cartridges.

_Poisonous Dose._--Dinitrobenzine is a potent poison, whether introduced into the stomach, injected into the circulation, absorbed as it readily is by the skin, or inhaled in the form of vapour.

The poisonous dose of dinitrobenzine for an animal, cat, or dog of six pounds in weight averages about .08 gramme; in the same proportion for a man of ten stones weight, it will be about 1.84 grammes.

Dixon Mann (_Forensic Medicine_, 2nd edition) and T. Oliver (article in Allbutt’s _System of Medicine_, vol. ii.) do not mention the poisonous dose, but in all probability a dose of under 1 gramme by the mouth will be lethal.

In fatal cases death takes place within twenty-four hours from a single dose. If animals live beyond that time, there is a strong probability of their ultimate recovery.

A marked characteristic of dinitrobenzine is the ease and rapidity with which, when mixed with fat, it passes through the skin into the system. We found that a 25 per cent. ointment in lanoline, rubbed into the skin of a cat, caused death in twenty-four hours, and 400 milligrammes of lanoline containing .1 gramme of dinitrobenzine, when rubbed into the groins of a man, produced lividity, cyanosis, and other pathognomonic symptoms in a few hours. No doubt the secretions of the cutaneous glands facilitate absorption when the powder settles on the skin. It is probable that all the nitro derivatives of the aromatic series pass readily through the skin. In most works, handling any of these crude compounds for any length of time without gloves is prohibited, being considered dangerous.

The concentrated vapour is dangerous in small doses, and fatal in large. A workman breathing for ten minutes the air in a flue through which pure dinitrobenzine had passed from the mixing pans, died from the effects eighteen hours later.

Judging from experiments upon animals, the poisonous dose, if injected hypodermically, is about half that taken by the mouth.

Poisoning divides itself naturally into acute, subacute, and chronic.

_Acute Poisoning._--Fatal acute cases are rare, and have been noted chiefly on account of their interest from a medico-legal point of view. The symptoms are nausea and vomiting, intense congestive headache, faintness and giddiness, loss of control over the limbs, numbness, tingling in tongue and lips, and other subjective sensations. A characteristic symptom is deep cyanosis; lips, fingers, and tongue are deeply cyanosed, nearly black in the early stage. The skin becomes cold and clammy, the pulse quick and weak, often over 120 a minute. It is small, thready, and feeble, and shows a very low condition of arterial tension. The capillaries are freely dilated, and cause the line of descent in sphygmographic tracings to be very rapid. In all severe cases the pulse is fully dicrotic, and displays well the loss of vasomotor tone, which is one of the most marked features in these cases. The heart’s action is easily excited by exertion, the breathing is laboured, and the urine darkened. The eyes become bright and glassy, the features pale and ghastly, and coma supervenes, which lasts for many hours. Exceptional symptoms are noises in the head, or dark specks floating before the eyes. When larger doses of the poison have been absorbed, unconsciousness may become complete. The eyes then roll slowly from side to side, the pupils are widely dilated, and the conjunctivæ are insensitive to touch. Both the deep and superficial reflexes are in abeyance. The respirations are increased to even double the normal number, become irregular, and Cheyne-Stokes in character. The limbs become quite flaccid, or one or more of the joints remain stiff, and when this is the case it is usually those of the upper limbs. Eventually this stiffness entirely disappears. The hands, feet, and face become remarkably bloodless. Occasionally there is œdema of the lips and eyelids, or dropsy of the lower extremities. The temperature ranges from 99° F. to 102° F. (_Lancet_, November 1, 1902, p. 89).

_Subacute Poisoning._--Subacute attacks may supervene upon chronic poisoning, in which, besides the usual chronic conditions to be mentioned later, we find a distinct distaste for food, especially breakfast. Sometimes there is nausea, or there may be slight vomiting. This should always be a warning sign, for, if neglected, coma may follow.

The attacks vary in severity according to the amount of the poison absorbed. The symptoms noticed are:--Headache, with throbbing of the temples and forehead, great langour and depression, the urine becomes darkened in colour, the hands moist; there is drowsiness, with great tendency to sleep; the men say it is impossible to keep awake. During the night they sleep soundly unless prevented by an incessant headache. In the morning they awake unrefreshed and heavy. The tongue is fairly clean though dark in colour, and develops a yellowish fur; dull, heavy pains are felt in the back. Breathing is quick and short, and fatigue follows upon the least exertion. Pricking, tingling, and numbness in the extremities are complained of when walking; workmen when so affected may take three hours to cover as many miles; they stagger, do not know where their legs are, frequently fall, and are unable to pick themselves up readily. When asked to walk backwards with their eyes closed, their movements are very unsteady. These symptoms practically disappear if the men leave work a few days; after such rest they say they feel in excellent health and spirits.

_Chronic Poisoning._--The more common manifestations may be denominated chronic, as they are found after prolonged absorption of small doses of the poison, and many of them persist for a long time, at least many months, even after the workmen have left this special occupation. All workers who are brought into intimate contact with this poison show more or less the following:--

Upon careful examination of the cases, it is found that those employed suffer from a very severe form of anæmia. The ruddy hue of health disappears; the skin becomes dirty yellow-greyish in colour. This duskiness gradually deepens with the amount of poison absorbed, and decreases as it becomes eliminated. This objective symptom is especially marked in the mucous membrane. The men appear to be suffering from partial asphyxia. The conjunctivæ show a jaundiced tinge.

_Muscular System._--The effects of the poison are shown in a marked manner upon the muscular system. The men have not the appearance of being employed in manual labour. When stripped the muscles are seen to be flaccid and the skin loose. The body lacks fullness and firmness. All movements lose tone and precision. Fatigue quickly follows muscular exertion.

In long-continued cases the objective symptoms are occasionally remarkable, such as wasting of the muscles, especially those of the extremities. This has been particularly pointed out by Dr Ross (_Medical Chronicle_, May 1889). “The muscles of the hands are seen to be very much atrophied. The spaces between the metacarpal bones are more distinctly marked than is normal, and the grooves between them very noticeable. The muscles of the thenar and hypo-thenar eminences are soft and distinctly wasted, especially the abductor indices. Patients cannot, without considerable trouble and difficulty, cause the tips of the thumb and little finger to meet. Sometimes this is more observable in one hand than the other. The phalangeal joints must be bent, otherwise there is inability to flex the thumb strongly into the palm, and at the same time the power of adduction is feeble.

“All the finer and more delicate movements of the hands are greatly restricted in severe cases. Small objects such as pins and needles cannot be readily felt or held. The act of walking loses much of its elasticity and spring, and in consequence the balance of the body is with difficulty maintained. The big toe in the advancing foot does not manifestly drop; it is only slightly flexed into the sole. There is usually no ankle drop, and the power of raising the toes whilst the foot is flat on the ground is not lost. The symptoms of weakness and paresis observed in the muscles of the foot are not so well-marked as those seen in the hand.”

_Nervous Symptoms._--Pains of a shooting, stabbing, or darting character are of very frequent occurrence. They are felt in all parts of the body, a common position being under the heart or in the armpit, neck, or jaws. The legs are rarely affected. When the pains are in the locality of the stomach they are of a griping nature. Sometimes a smarting or burning sensation is described, which is felt in the cheeks, forehead, and eyes, or restricted to the soles of the feet. These sensations are not accompanied by tenderness to the touch.

More or less irritation of the peripheral nerves is always present. It shows itself by tingling and itching of the skin of the fingers, palms, and backs of the hands, sometimes extending to the wrists. In a certain proportion of cases they are felt in the feet as well as the hands. They may be restricted to the feet, and only noticed when the men have their boots on, or their legs crossed. Whilst sitting, or at rest in bed, the pains are often acute. They are invariably confined to the dorsum of the foot, never being felt in the soles, and disappear upon standing or walking. Occasionally these symptoms are more severe in the extremity or extremities of one side of the body.

Hyperæsthesia is a most characteristic feature in all these chronic cases of poisoning. In all cases it is present, but it varies both in intensity and in the part of the body affected. It may be felt in one or both feet, restricted to the upper or under surfaces of the toes. Striking the outside, or dorsum of the foot, causes severe electric-like pains to run all over the leg. In a well-marked case there will be exceeding tenderness upon the slightest pressure on any part of the foot. Drawing the finger very gently over these sensitive areas sends shooting pains about four inches up the legs. The soles of the feet are not affected by a light touch, but a sharp blow, tap, or jar, or a false step in walking causes painful sensations as high as the knees. These symptoms are usually more acute in the left than the right leg. The upper extremity is in like manner affected; a gentle rub on a small part of the cutaneous distribution of the ulnar nerve will produce general formication and tingling all over the arm. Partial hemianæsthesia, with a small patch excessively tender, may be present. This is probably hysterical. Dr Dreschfeld points out that Charcot, Balmskz, and Marie have found this same symptom in bisulphide of carbon poisoning, viz., hemianæsthesia with small circumscribed hyperæsthetic areas. The nerve trunks of the legs or arms are sensitive to pressure where superficial; and great pain is caused all over the area of distribution of the occipital nerve by pressure on the nerve trunk.

The muscles are often very tender, especially those of the upper arm. Touch is often impaired in the fingers and toes. Patients almost invariably complain that the skin of the hands and soles of the feet is less sensitive than is usual in the healthy state. The fingers are numb and act clumsily, while the hands feel as if they were gloved. The impression of sand or snow is conveyed to the feet when standing or walking. Heat and cold are with difficulty differentiated. In one sufferer two test-tubes containing water, differing 10 degrees in temperature, being applied to the arms and trunk, were readily distinguished, but from the hips downwards the patient was utterly unable to discover which of the two tubes was the hotter. If applied simultaneously about three inches apart, both were experienced as cold. Generally speaking the skin of the body is more sensitive than that of the limbs, but in all parts variations occur. Upon using a Faradic current of a given strength, which was with difficulty borne by the thighs, arms, and trunk, there was no perceptible impression produced in the calves or legs. In these situations the compasses must be separated three inches, to be distinguished as two points. The transmission of touch and pain are slower than normal, or at any rate are not as readily responded to as in health. The extremities become very quickly chilled. On the slightest exposure to a low temperature the fingers look pale, bloodless, and feel as if they were dead, and the feet are always cold. Hearing and taste are unaffected. There is great loss of energy. Feebleness, lassitude, and depression are invariable concomitants. The sexual appetite is notoriously weakened, or lost, and erections of the penis rare. The reflexes, superficial and deep, are very variable; sometimes they are exaggerated; this, however, is not usual. Generally speaking, they are enfeebled. Dr Reynolds mentions a case where the patient was comatose and the knee-jerk persistent. Cremasteric and plantar reflexes are those most commonly absent. The muscles react readily to a moderate Faradic current, but different groups of muscles vary in their sensitiveness to the same strength of current.

_Eye Affections._--Dinitrobenzine produces a distinct toxic defect of vision similar in many respects to that caused by tobacco, iodoform, bisulphide of carbon, etc. This amblyopia will be found in a varying degree in all those who suffer periodically from subacute attacks of poisoning, or who develop other symptoms due to the continued absorption of the poison. Susceptibility may aggravate the symptoms, but no worker can claim perfect immunity. Comparatively few complain of any impairment to their sight, but probably about one in ten are unknowingly affected. Dr Neiden (_Edinburgh Medical Journal_, 1889) and Mr Simeon Snell (_British Medical Journal_, 1894) have described the eye affections. The latter summarises his conclusions as follows:--“Failure of sight, often to a considerable degree in both eyes, concentric contraction of the visual field, with in many cases a central colour scotoma, some blurring, never extensive, of the edges of the disc, and a varying degree of pallor of its surface.”

In all cases absence from the work removes these symptoms in a varying length of time: and usually a restricted exposure will alleviate them.

_Urinary Affection._--In cases of long-continued chronic poisoning, dinitrobenzine will always be found free in the urine (Dixon Mann). In the urine of animals, tube casts, brown flakes, and hæmoglobin have been isolated, and in the kidneys much cloudy swelling of the epithelium lining the tubules can be seen (Strassmann and Strecker).

We tested the blood, lungs, liver, spleen, and urine from several cats poisoned by dinitrobenzine. In only one sample, the urine from a cat which died from chronic poisoning, could any indication be found. Both sugar and albumen are generally absent. The source of the bile pigments is the hæmoglobin of the blood, and the excretion of these pigments points to the existence of some cause at work in the blood leading to the destruction of hæmoglobin. The large deposit of urates, high specific gravity and presence of biliary pigments found in the urine, is strong corroborative evidence of an active destruction of blood corpuscles.

No experimental evidence has yet proved that reduction takes place in the body in case of the nitro-compounds of benzine to aniline, or phenylene-diamine.

In several samples of urine tested, both nitrates and nitrites were present, so that in the case of phenylene-diamine being present, the pigment Bismarck brown would be formed, and would give the urine a brown tint.

The samples of urine were tested for free dinitrobenzine by the following method: The urine is treated with zinc and hydrochloric acid for some hours. Any dinitrobenzine that may be present is reduced by the nascent hydrogen into phenylene-diamine. The urine is then alkalised with caustic soda, and well shaken up with ether. The ether is then separated, filtered, and evaporated. The residue is treated with dilute acetic acid and nitrite of soda, when a yellow or brown coloration shows the presence of dinitrobenzine in the original sample. In three cases a slight indication was found.

By ordinary reducing agents in the laboratory, such as nascent hydrogen, the nitro-substitution compounds of benzine can easily be reduced as follows:--

Mononitrobenzine to aniline.

Dinitrobenzine to phenylene-diamine.

Trinitrobenzine to triamidobenzine.

The amount of urea is generally high, due to increased metabolism of the tissues.

The exact chemical changes which take place in the body are extremely difficult to follow. The nitro-compounds probably pass through the body without suffering any change, or they may be reduced in the body.

It will be noticed in the subsequent table that all the samples are acid, many being strongly so. Nearly all are dark-brown in colour and generally precipitate a red deposit, principally urates. In most of these urobilin is present, and can be easily recognised by the following test: 100 c.c. of the urine are acidified with 10 drops of strong hydrochloric acid, and then shaken with 20 c.c. of chloroform. The chloroform which falls to the bottom is separated by means of a separating funnel, and filtered into a test-tube, .4 c.c. of a solution of 1 gramme of crystallised acetate of zinc dissolved in a litre of 95 per cent. alcohol is then poured gently down the side of the test-tube, and at the junction where the liquids meet, a green fluorescent ring, characteristic of urobilin, will appear; the solution on shaking will become fluorescent, being green by transmitted, and rose-coloured by reflected light. This pigment can also be detected by means of the spectroscope.

_Urine._--In severe cases of dinitrobenzine poisoning, the urine becomes of a dark, tawny, port-wine colour. There is no irritation or frequency in making water.

The following table represents the examination of the urine from very mild cases, such as can any day be found amongst men handling, or breathing the fumes of dinitrobenzine.

_Pathology: The Blood._--Active metabolism takes place at once upon contact of the blood tissue with dinitrobenzine, and this may induce a febrile rise of temperature. The blood becomes thin and dark in colour, varying from chocolate-brown to black. The number of blood corpuscles is greatly diminished, in some cases less than half the normal number. The amount of hæmoglobin averages 35 per cent. MacMunn describes the presence of large coloured megalocytes, 12 µ in diameter; the ordinary red corpuscles are smaller than normal, about 5 µ or 6 µ in diameter; many are crenated and broken up.

Haldane (_Journal of Physiology_, vol. xxi., 1897), in carefully conducted experiments on mice, “finds spectroscopically a feebly-marked band in the red besides the oxyhæmoglobin bands; but it was not methæmoglobin. Methæmoglobin is contained in the blood, but some other pigment is probably present.” In men we were able to obtain the oxyhæmoglobin band, but it was always blurred. Whether there is a special dinitro band in the blood is a disputed point; it has been investigated in animals by Huber and Röhl (_Über akute u. chron. Intox durch Nitrokorp d. Benzolreihe_, 1890).

_URINARY ANALYSIS_

+---+-------------+----------------+-----------+-----------+
|No.| Sp. Gr. | Appearance. | Colour. |Reaction to|
| |Water = 1000.| | | Litmus. |
+---+-------------+----------------+-----------+-----------+
| 1 | 1029 | Clear | Red brown | Acid |
| 2 | 1030 | Clear | Yellow | Acid |
| 3 | 1024 |Slight pp. mucus| Yellow | Acid |
| 4 | 1021 |Slight pp. mucus| Red brown | Acid |
| 5 | 1025 | Heavy red pp. | Red brown | Acid |
| 6 | 1027 | Clear | Red brown | Acid |
| 7 | 1026 |Thick white pp. |Pale yellow| Acid |
| 8 | 1026 | Red deposit | Red brown | Acid |
| 9 | 1022 | Red deposit | Red brown | Acid |
|10 | 1022 | Clear | Yellow | Acid |
|11 | 1027 | Red deposit | Red brown | Acid |
|12 | 1025 | Red deposit | Red brown | Acid |
|13 | 1024 | Red deposit | Red brown | Acid |
+---+-------------+----------------+-----------+-----------+