Chapter XIII: Part II: The Symptoms and Treatment of Industrial Poisoning (2)

The points Armit investigated experimentally were (1) Is the carbon monoxide of the compound wholly or partly responsible for the symptoms, or (2), is nickel carbonyl absorbed as such, or (3), is it the nickel of the compound which produces the symptoms? His conclusions are that the poisonous effects of nickel carbonyl are entirely due to the nickel of the compound. The peculiar toxicity is due to the fact that, being introduced in a gaseous form, the nickel is deposited as a slightly soluble compound in a very fine state of subdivision over the immense area of the respiratory surface. Nickel carbonyl when mixed with air cannot be absorbed as such by an animal as it becomes split up into the nickel containing substance (possibly hydrated basic carbonate of nickel) and carbon monoxide before or soon after reaching the alveoli of the lungs. The nickel is dissolved from the respiratory surface by the tissue fluids and is then taken up by the blood. The hæmorrhages found after death follow as the result of fatty degeneration of the vessel walls which is the specific pathological change set up by nickel.]

=Copper.=—Symptoms which have been described by some writers as chronic industrial copper poisoning are probably due to admixtures of other poisonous metals, especially lead and arsenic. Although some copper workers, especially those careless of cleanliness, exhibit hair and teeth coloured by the action of copper compounds (green tinge on hair and edge of teeth), symptoms of illness traceable to copper are not demonstrable.

_Brass-founders’ fever_, which by some earlier writers was ascribed to copper or combined copper and zinc action, is traceable to zinc (see Zinc).

=Ferro-silicon.=—The illnesses due to this are phosphoretted or arseniuretted hydrogen poisoning (see pp. 191 and 197).

=Silver and Silver Compounds.=—Gradual absorption of small quantities of a solution of silver may produce industrial argyria, often beginning with the appearance of a black edge to the gums and darkening of the hair and nails, followed by black spots on the skin which in severe cases coalesce, so that the whole or almost the whole surface of the body becomes black and glossy.

Argyria is due to the absorption of silver compounds into the circulation, and subsequent deposition of the reduced silver in the body (liver, kidneys, spinal cord, &c.). The black colouring of the skin is caused by the action of light.

No interference with health worth mentioning is observed.

_GROUP: ARSENIC, PHOSPHORUS_

The poisons (gradually absorbed) belonging to this group are mainly such as affect metabolism; they impair the processes essential to metabolism (in especial the oxidation processes) and cause severe damage to the cells, through destruction of albumen. The poisons of this group also have a paralysing effect upon the central nervous system.

Generally speaking the effects produced by the poisons of this group vary considerably. Among the arsenic compounds arseniuretted hydrogen, which is supremely a blood poison, must be excluded from the group and included among the blood poisons.

ARSENIC, OXIDES OF ARSENIC

Pure _metallic arsenic_ (As) is considered innocuous. _Oxides of arsenic_ especially are held to be industrial poisons such as arsenic trioxide (As₂O₃), the anhydride of arsenious acid (H₃AsO₃), a white powder, which is known under the name of white arsenic; _arsenic acid_ (H₃AsO₄), which forms crystals easily soluble in water, and the salts of these acids, especially copper arsenite, formerly employed in the production of dyes, and also _arsenic chloride_ (arsenic trichloride, AsCl₃). _Arseniuretted hydrogen_ will be treated separately as it has a completely different poisonous effect from that of the oxidic compounds of arsenic. _Arsenic sulphides_ (realgar, AsS₂, and orpiment, AsS₃) are regarded as innocuous in consequence of their insolubility in a pure state. But it may be remarked that arsenic sulphides (sulphur arsenic ores) which are used industrially, and even metallic arsenic, are to be considered poisonous, as they contain oxidic arsenic compounds in great quantity.

Chronic arsenical poisoning is caused by gradual absorption through the respiratory or digestive tracts of small quantities of the oxidic arsenic compounds either in solution or as dust or fumes.

The disease usually begins with digestive derangement which shows itself in more or less severe gastric and intestinal catarrh (loss of appetite, vomiting and diarrhœa); sometimes there are severe affections of the respiratory tract,—pharyngeal and bronchial catarrhs; often the illness is accompanied by skin affections of various kinds, rashes, pustular eczema, loosening of the nails, abscesses, dark pigmentation of particular parts of the skin, and other symptoms. The nervous symptoms vary much according to the severity of the disease; first of all, deafness and feeling of pins and needles, or loss of sensation (paræsthesia and anæsthesia) of the extremities. Further, rheumatic joint pains, weakness of the extremities and characteristic symptoms of paralysis occur, with accompanying atrophy of the muscles, and gradual loss of energy leading to total incapacity for work. Severe cases end in general exhaustion and loss of strength, with signs of severe injury to the central nervous system, such as epileptic fits, mental hebetude, &c.

PHOSPHORUS

_Phosphorus_ (P) is polymorphic; red (amorphous) phosphorus is innocuous, while white or yellow is poisonous. Phosphorus at various stages of oxidation is little if at all poisonous. White phosphorus is volatile and fumes in the air—the fumes consisting of phosphorus, phosphoric and phosphorous acids.

Chronic industrial phosphorus poisoning is produced by continued inhalation of the fumes of white phosphorus resulting in inflammation of the periosteum of the bone, with which necrosis and formation of new bone are associated. It attacks especially the lower jawbone (ossifying periostitis). The inflammation begins with increased flow of saliva, painful swelling of the gums, which, as it increases, brings about the death of the jawbone (necrosis, phosphorus necrosis). This becomes covered again with newly formed bone substance from the periosteum. The process ends with the formation of a fistula (a passage filled with pus), which discharges outwards, and through which the dead bone (sequestrum) is eventually cast off. Occasionally the process attacks the upper jaw, rarely other bones.

With these characteristic symptoms of phosphorus necrosis, derangement of nutrition together with anæmia, indigestion and bronchial catarrh, may be associated. Further, a general brittleness of the bones (fragilitas ossium) is observed with the result that the long bones of the leg or arm sometimes break at relatively small exertion of force; such cases from Bohemia came lately under my notice.

Some authorities regard caries of the teeth as the pre-disposing cause of phosphorus necrosis; according to this view the carious teeth constitute the means of entrance for the poison. Opposed to this so-called ‘local’ theory is the view that chronic phosphorus poisoning is a ‘general’ one. The truth may lie midway. On the one hand phosphorus necrosis probably arises partly from the general poisonous action of the phosphorus, and on the other from local inflammation which leads to the occurrence of local symptoms. The general symptoms of chronic phosphorus poisoning described above support this view, especially the effect observed on the bones of the skeleton. This view is also strengthened by the fact that workmen with perfectly sound teeth, who had been exposed to phosphorus fumes for many years, were attacked by necrosis only when traumatic inflammation produced by chance injury was set up.

The treatment of phosphorus necrosis is surgical. Formerly the treatment recommended was to wait for formation of new bone and exfoliation of the dead bone (expectant treatment); the necrosed portions of bone were then extracted through the fistula. Recently early operative interference has succeeded in preserving the periosteum which enabled the new bone to form.

Phosphoretted Hydrogen

Industrial poisoning by gaseous phosphoretted hydrogen (PH₃) calls for attention in connection with the preparation and employment of calcium carbide (acetylene) and also of ferro-silicon.

Phosphoretted hydrogen is a dangerous poison. Even 0·025 per cent. in the air is harmful to animals after a time; 0·2 per cent. PH₃ in the air quickly causes death.

The poison produces changes in the lungs, though without injuring the respiratory passages by corrosion, and finally has a paralysing effect upon the central nervous system. It has no effect upon the blood. An autopsy on a person who has died of phosphoretted hydrogen poisoning reveals as a rule no characteristic sign, except centres of inflammation in the lungs.

The symptoms of phosphoretted hydrogen poisoning are—difficulty of breathing, cough, fainting fits, noises in the ears, and nausea; in severe cases coma and death. Slight cases soon recover without after-effects.

_GROUP: SULPHURETTED HYDROGEN, CARBON BISULPHIDE, AND CYANOGEN (NERVE POISONS)_

In this group are comprised industrial poisons the principal effect of which is upon the nervous system, especially the central nervous system. The chemical composition of the separate members of the group differs much.

SULPHURETTED HYDROGEN

Industrial poisoning by pure sulphuretted hydrogen (SH₂), the well-known colourless, nauseous-smelling gas, occurs comparatively rarely. Poisoning is generally acute, but chronic illness in workers has been traced back to inhalation of the gas.

This poison exerts a paralysing action upon the central nervous system and is slightly irritating to the mucous membranes and respiratory organs.

Its action can be described as follows: When absorbed into the blood union of the poison with the alkaline constituents takes place with formation of an alkaline sulphide. Presence of only slight quantities of sulphuretted hydrogen in the air acts injuriously. Lehmann has shown that about 0·15 to 0·2 per thousand sulphuretted hydrogen is not without effect, and that prolonged inhalation of 0·5 per thousand becomes dangerous. Continued exposure to the poison seems only to increase susceptibility to its action. An almost complete absorption of the whole of the sulphuretted hydrogen present in the air breathed takes place.

Continued inhalation of small quantities of sulphuretted hydrogen produces irritation of the mucous membrane, cough, and lacrymation; headache, giddiness, nausea, and mental dulness soon ensue; occasionally also symptoms of intestinal catarrh follow; if at this stage—or after a longer exposure to the action of a smaller amount—the patient is withdrawn from its further influence, there still continue for some time symptoms of irritation of the mucous membrane (such as inflammation of the conjunctiva and of the respiratory passages).

Further exposure or absorption of greater amounts induces general discomfort and passes on to a second stage of convulsions and delirium.

Inhalation of a large dose of sulphuretted hydrogen causes almost instantaneous death; the affected person falls dead—often without a sound—as if struck by a blow; occasionally a short stage of unconsciousness, with symptoms of suffocation, precede death.

This acute form often occurs, especially in acute sewer gas poisoning. Besides this, a sub-acute form of sewer gas poisoning is recognised which is attributable, in part at least, to the action of sulphuretted hydrogen, the prominent symptoms being irritation of the mucous membranes and of the intestinal canal. In other severe cases symptoms of the central nervous system preponderate (headache, giddiness, and delirium). These forms of poisoning can be caused not only by sulphuretted hydrogen, but also by other poisonous gases which are found in drains or sewers.

As regards treatment, continued inhalation of oxygen, supported by artificial respiration, is often, in serious cases, effective. In severe poisonings also saline injections and bleeding may be advocated. Other symptoms (catarrh, &c.) must be treated symptomatically.

CARBON BISULPHIDE

Pure carbon bisulphide (CS₂) is a colourless, peculiar-smelling liquid which boils at 46° C.

As Lehmann has shown, even 1·5 to 3·0 mg. CS₂ per litre of air produces distress—with acute symptoms of poisoning (congestion, giddiness, sickness, &c.).

Industrial carbon bisulphide poisoning is, however, chronic in nature and induced by continuous inhalation of small quantities of the fumes. To understand the action of carbon bisulphide, its capacity for dissolving fats and fatty substances must be taken into account. Its injurious effect extends to the nerve tissues (central and peripheral nervous system) and the glandular tissues.

Throughout chronic industrial carbon bisulphide poisoning, which has been described fully by Delpech, Laudenheimer, and others, nervous and psychical symptoms predominate, together with severe chronic digestive derangement.

The patient after exposure for some time suffers from violent headache, giddiness, and sickness; he has sensations of cold, pains in the limbs, a feeling of ‘needles and pins,’ and itching in different parts of the body. Gradually a condition of general excitement develops. Sleeplessness, cramps, and palpitation set in. At the same time the nervous system becomes involved—hypersensitiveness, loss of sensation or complete numbness of some parts of the skin, diminution of muscular power, disturbances of movement, twitching, violent trembling, wasting of the muscles, and paralysis; the sight also is sometimes affected. The stage of excitement, in which the patient often becomes strikingly loquacious without cause, passes gradually, as the nervous symptoms develop, into the stage of depression; sometimes this takes weeks and months; excitement and gaiety give place to deep depression; other symptoms appear—weakness of memory, mental dulness, and difficulty in speaking. The powers of sensation become affected, paralysis increases, and digestive disturbances, anæmia, and general loss of strength are manifest. Occasionally definite mental disease (psychosis, mania, melancholia, dementia, &c.) develops.

Certain cases of chronic carbon bisulphide poisoning in indiarubber workers have come under my notice, and some remarks concerning them may be of interest. The characteristic symptoms are essentially as follows: the invalid appears in the consulting-room in a bent position, leaning upon a stick with head and hands shaking. The gait is clumsy (spastic-paralysis) so that the patient ‘steps’ rather than walks. When seated, the tremor ceases to some extent, but in purposive movements increases rapidly, involving the whole body, so that an exact systematic examination becomes impossible, and the invalid sinks back into the chair exhausted and bathed in perspiration. He complains of cold in the extremities. He looks pale; the skin of the upper extremities is totally without feeling, as also is the upper part of the feet; the skin of the head is hypersensitive; the muscular strength of the arms is almost lost; testing the strength brings on marked shaking, followed by a fainting-fit caused by exhaustion. The extremities of the patient are cyanotic (livid); the knee jerks are exaggerated. The patient suffers from indigestion, constipation, headache, and giddiness; he is irritable, and depressed; his memory is weak; mental derangement cannot be proved.

Chronic carbon bisulphide poisoning is rarely fatal. Slight cases end in recovery after more or less long continuance; in severe cases improvement occasionally takes place, but serious nervous disturbance (paralysis, weakness of the muscles, deterioration of intellect) usually persists.

Treatment is symptomatic, aiming especially at relieving the nervous symptoms and improving the state of nutrition. If psychical disturbances are prominent, treatment in an institution is necessary.

CYANOGEN AND CYANOGEN COMPOUNDS (CYANOGEN GAS, PRUSSIC ACID, CYANIDES)

Industrial cyanogen poisoning is not frequent. _Cyanogen gas_ (C₂N₂, existing in small quantities in furnace gas, illuminating gas, and other kinds of gas) and especially _hydrocyanic acid_ (CNH, prussic acid) are considered industrial poisons; the latter is a very unstable, colourless, pungent-smelling liquid, boiling at 27° C. Among the cyanides employed industrially and having an effect similar to that of prussic acid must be mentioned _cyanide of potassium_ and _cyanide of sodium_ (KCN and NaCN), _cyanide of silver_ (AgCN) and _cyanide of mercury_ (Hg[CN]₂).

Cyanogen and cyanogen compounds are extraordinarily powerful poisons. The minimum dose lies, as Lehmann has proved by experiments on animals, at about 0·05 per thousand of hydrocyanic acid in the atmosphere breathed; 1-5 mg. per kg. weight is fatal to animals; to man about 60 mg. would be fatal.

The poisonous action of cyanogen and cyanogen compounds depends upon their power of preventing absorption of oxygen from the blood by the tissues with the result that the venous blood flowing to the heart retains the bright red colour which otherwise only arterial blood exhibits. This effect is due to cessation of the gaseous exchange in the body, and results in tissue suffocation. At the same time these poisons have at first an exciting and then a paralysing effect upon the central nervous system. In severe poisoning the nerve effect is masked by the effect upon the exchange of gases in the blood, since this quickly leads to death.

Most of the cases of industrial poisoning under this heading result from inhalation; absorption of liquid cyanogen compounds through the skin can rarely come into consideration.

If large quantities of hydrocyanic acid have been inhaled, death ensues very quickly. The person affected falls down suddenly, breathes with difficulty, the pulse soon becomes imperceptible, and after a more or less long stage of deep unconsciousness (coma) life becomes extinct.

In slight cases of poisoning the patient feels a sensation of irritation in the throat, giddiness, sickness, and difficulty in breathing; occasionally such disturbances persist for some time.

Some writers have described symptoms in workers manipulating prussic acid and cyanides, which they believe to be due to chronic prussic acid poisoning. Complaint is made of oppression of the chest, throat irritation, giddiness, difficulty in breathing, palpitation, hebetude, exhaustion, and nausea and vomiting; in certain instances the attack, aggravated by exhaustion and weakness, culminates in death. It is a question whether such poisonings are chronic in the true sense of the word. In view of the mode of action of hydrocyanic acid, such cases of sickness should rather be accounted acute or sub-acute poisonings through repeated action of small quantities of the poison.

It may be mentioned that in persons working with alkaline cyanides (especially in electro-plating) skin affections occasionally occur; these are traceable to the caustic effect of alkaline cyanides.

Treatment by oxygen inhalation with simultaneous artificial respiration holds out most prospect of success. This holds good for acute poisoning by the other poisons belonging to this group. Besides this, saline injections and bleeding are recommended, and also the administration of an infusion of sodium thiosulphate solution.

_GROUP: ARSENIURETTED HYDROGEN AND CARBONIC OXIDE (BLOOD POISONS)_

Included in this group, as in the former one, are substances chemically very different from each other, but of which the action is especially on the blood. Besides this common effect, these substances also produce various other effects, such as local irritation, effect on the nervous system, &c. The industrial blood poisons, which according to their chemical constitution are classed among the aliphatic and the aromatic series of organic compounds, will, for the sake of clearness, be discussed in the following chapters.

ARSENIURETTED HYDROGEN

Acute arseniuretted hydrogen poisoning, produced by inhalation of relatively very small quantities of arseniuretted hydrogen gas (AsH₃) is in most cases industrial in origin. The absorption of an amount corresponding to about 0·01 mg. arsenic suffices to produce severe poisoning symptoms. The poisonous effect results chiefly from action upon the red blood corpuscles, which are dissolved (hæmolysis). Arseniuretted hydrogen is therefore a genuine blood poison. The effect upon the blood, if not immediately fatal to life, is to cause the dissolved blood-colouring matter to pass into the tissues where, though some is deposited, most goes to, and acts injuriously on, the organs, especially the liver, spleen, and kidneys. In cases running at once a fatal course, the impoverishment of the blood caused by the lack of colouring matter necessary to internal respiration produces tissue suffocation, which is therefore the primary cause of death. In cases not immediately fatal, the injury to the functions of the organs alluded to (for instance, cessation of the functions of the kidneys, &c.) may lead to death secondarily.

Symptoms of the disease appear often only some time after the poisoning has set in, and begin with general malaise, sickness, collapse, fainting fits, and difficulty of breathing; after some hours the characteristic signs follow—the urine becomes dark red to black, containing quantities of blood colouring matter and dissolved constituents of the blood, and later also bile colouring matter, so that a coppery jaundice comes on if the illness is prolonged. The region of the liver, spleen, and kidneys is painful. Severe cases often end fatally during the first stage of the illness, more rarely later, with increased difficulty of breathing; sometimes death occurs after a preceding comatose stage marked by convulsions and delirium. In slighter poisoning cases the symptoms abate in a few days and recovery follows.

The treatment of arseniuretted hydrogen poisoning is similar to that adopted in the case of all other blood poisonings: in addition, if possible, direct transfusion of blood from the artery of the giver into the vein of the receiver, liquid nourishment, saline injections, and, above all, prolonged oxygen inhalation.

CARBONIC OXIDE (CO)

Carbonic oxide (CO) is a colourless, odourless gas which frequently causes both acute and, it is said, chronic industrial poisoning.

Carbonic oxide is a very poisonous gas; even as little as 0·5 per thousand in the atmosphere breathed has a poisonous effect; about 2-3 per thousand can be dangerous to life.

Its poisonous effect results from its power of combining with the blood-colouring matter or hæmoglobin to form carboxy-hæmoglobin; the affinity of carbonic oxide for the hæmoglobin of the blood is more than 200 times greater than that of oxygen, so that, however small the amount of carbonic oxide in the air, it is inevitably absorbed by the blood and retained. The blood so altered, assumes a cherry-red colour, is unable to effect the necessary exchange of gases for internal respiration, and in consequence of the lack of oxygen suffocation ensues.

Without doubt, however, carbonic oxide has also an immediate effect upon the central nervous system (first excitation, followed quickly by paralysis). It is maintained also that besides the action upon the hæmoglobin it favours coagulation of the blood through the disintegration of the blood corpuscles. The last-mentioned action is thought to account for the sequelæ of carbonic oxide poisoning, but they can also naturally be accounted for by the direct effect of the poison.

Onset of symptoms is very sudden if a large quantity of pure carbonic oxide is inhaled. The affected person immediately falls down unconscious and succumbs after drawing a few breaths with difficulty.

In less acute cases the illness begins with premonitory symptoms, generally headache, sickness, giddiness, sleepiness, though in cases of fairly rapid absorption these are absent, and are naturally absent also when the poisoning creeps upon the affected persons while asleep, as occasionally happens in cabins, &c., in factories. If the poisoning continues, increasing mental dulness, accompanied by nausea and vomiting, leads sometimes to a short stage of seemingly drunken excitement, which preludes deep unconsciousness during which there is often a convulsive stage, followed by complete loss both of sensation and of reflex action; the breathing becomes shallow and intermittent, the pulse small and irregular, and finally death ensues. Occasionally in the stage of unconsciousness, death is hastened by entrance of vomited matter into the respiratory passages. Bright red patches are seen on the body after death.

If persons affected by severe carbonic oxide poisoning are withdrawn from the poisonous atmosphere after having reached the stage of unconsciousness, they may recover, but often with difficulty; not infrequently—in spite of suitable treatment—death occurs some considerable time later from the symptoms described above. Still, in many cases, under the influence of right treatment, gradual recovery has been brought about, even after long unconsciousness accompanied by repeated convulsions. In the rescued the symptoms described as characteristic of the first stage often continue for at least a day. Further, they are liable to a number of serious after effects, such as severe inflammation of the lungs due to infection by the entrance of vomited matter into the air passages, skin affections (rashes), and especially severe nervous and mental affections. Frequently these develop from centres of softening in the brain or from inflammation of the peripheral nerves (neuritis); occasionally the poisoning may really only be the predisposing cause for the outbreak of an existing psychical disease. It is not our task to enumerate all the extremely varied disturbances which are observed after carbonic acid gas poisoning. Neuralgias and paralyses have been described as associated with the peripheral nerve symptoms over areas supplied by different nerves; various forms of diseases of the brain and spinal cord (poliomyelitis, paralysis, sclerosis, &c.); and finally a series of psychoses (neurasthenia, melancholia, mania, &c.), occasionally passing into dementia and imbecility. Glycosuria (sugar in the urine) has also been noted as a sequela.

Chronic carbonic oxide poisoning, arising from continued inhalation of small quantities of the gas, sets in usually with symptoms similar to those of acute carbonic oxide poisoning; if the worker continues exposed to danger, severe symptoms may arise which point to marked alteration of the blood and later also of the digestion and bodily functions. Under certain circumstances severe nervous and mental affections are said to occur similar to those which we have mentioned as sequelæ of acute carbonic oxide poisoning (convulsions, disturbances of mental activity, symptoms which resemble progressive muscular atrophy, &c.).

In acute carbonic oxide poisoning oxygen inhalation indefatigably continued and supported by artificial respiration is often successful. The serious danger from this form of poisoning renders it very necessary that in all premises where there is risk provision should be made for the administration of oxygen. The sequelæ can of course only be treated symptomatically.

OXYCHLORIDE OF CARBON (PHOSGENE)

Oxychloride of carbon (COCl₂), also called phosgene, is, at the ordinary temperature, a colourless gas with a disagreeable smell. This decomposes in moist air into carbonic oxide, hydrochloric acid, or chlorine, and produces a strongly irritant local effect upon the mucous membranes. Industrial poisoning by phosgene is characterised by great difficulty in breathing and inflammation of the respiratory tract (bronchitis and bloodstained expectoration).

Several cases have been treated successfully by oxygen inhalation.

NICKEL CARBONYL

The effects of nickel carbonyl are described on pp. 186-8.

CARBONIC ACID

Carbonic acid (CO₂), a colourless gas, is heavier than air (specific weight, 1·526), and therefore, wherever it collects, sinks to the ground. Carbonic acid is only very slightly poisonous; about 10 per cent. carbonic acid in the air causes asphyxia. The extinguishing of a candle flame will serve as an indication that the amount of carbonic acid in the atmosphere has reached this point. Cases of industrial carbonic acid asphyxia are sudden; they do not occur frequently.

The gradual action of the gas when mixed with air produces first a tingling sensation on the surface of the body, reddening of the face, irritation of the mucous membrane and the respiratory organs, after which succeed difficulty in breathing, palpitation, fainting, and unconsciousness.

Sudden and fatal poisoning occurs industrially. Upon entering places filled with carbonic acid gas the affected person falls down dead almost immediately. These are cases of asphyxia, in which the lack of oxygen certainly plays the greatest part. If those affected by acute carbonic acid poisoning are removed in time out of the dangerous atmosphere they usually recover quickly.

Oxygen inhalations and artificial respiration are to be applied in severer cases. There are no sequelæ.

_GROUP: HYDROCARBONS OF THE ALIPHATIC AND AROMATIC SERIES AND THEIR HALOGEN AND HYDROXYL SUBSTITUTION PRODUCTS_

The industrial poisons comprised in this group have as their principal general effect injurious action upon the functions of the central nervous system (paralysis or causing excitation) which is prominent in most of the cases of industrial poisoning caused by these substances. This effect is most marked in the case of the readily volatile (low boiling) hydrocarbons, while those less volatile and boiling at a higher temperature often have collateral effects (such as local irritation). The characteristic poisonous effect caused by the chlorine and hydroxyl-substitution products (chloroform and alcohol group) is also mainly on the central nervous system (narcosis).

HYDROCARBONS OF MINERAL OIL

BENZINE, LIGROINE, PETROLEUM, PARAFFIN, VASELINE

_Mineral oil_ (crude petroleum) has, according to its origin, differing composition. Thus in American mineral oil hydrocarbons of the methane series preponderate; in the Russian, hydrocarbons of the aromatic series. Reference has been made in Part I. to this point, as well as to the separation of crude petroleum into its different fractions.

The injury to health produced by crude petroleum and its derivatives is of two kinds. Direct contact with liquid petroleum and the semi-liquid and solid deposit after distillation (paraffin) cause local injury to the skin. Inhalation of the volatile constituents of raw petroleum causes symptoms affecting mainly the central nervous system. They have moreover a markedly irritating effect upon the mucous membrane of the respiratory organs. These substances clearly exhibit the characteristic we have referred to, namely, that the hydrocarbons boiling at low temperature act as nerve poisons, whereas those boiling at a higher temperature produce a local irritant effect.

The skin affections take the form of inflammation of the hair follicles (acne), eruptions with characteristic formation of vesicles, and pimples and pustules which precede the deep-seated formation of ulcers, abscesses, &c.

In paraffin workers the acne-like skin inflammations are known as ‘paraffin eczema.’ They develop sometimes into cancer of the skin (warty and epitheliomatous growths).

In the general poisoning produced by inhalation of petroleum fumes the effect upon the central nervous system is all the more plainly and clearly marked when the irritant effect of the hydrocarbons boiling at higher temperature is slight or absent; that is, in the case of poisoning which arises solely from industrial products of low boiling hydrocarbons; among these benzine is included.

Acute poisoning from inhalation of benzine fumes begins with headache, sickness, and attacks of giddiness resembling alcoholic intoxication. If very much has been inhaled, the patient quickly becomes unconscious, with occasionally muscular tremors, convulsions, difficulty in breathing, and cyanosis.

In cases of poisoning by inhalation of fumes of crude petroleum, these symptoms may be complicated by coughing, intense inflammation of the mucous membrane of the respiratory organs—congestion, bronchitis, bloodstained expectoration, and inflammation of the lungs. In workers who frequently remain long in an atmosphere filled with benzine fumes, further symptoms of chronic benzine poisoning show themselves—mental hebetude, pains in the limbs, trembling, weakness of the muscles, and other disturbances of the nervous system; in such cases these may really be signs of continued attacks of acute or sub-acute poisoning; many benzine workers are anæmic.

The treatment of acute benzine poisoning consists in oxygen inhalation, with simultaneous artificial respiration. Treatment of chronic derangement of health is symptomatic.

HYDROCARBONS OF THE AROMATIC SERIES

BENZENE AND ITS HOMOLOGUES

_Benzene_ (C₆H₆) is a characteristically smelling (aromatic) liquid which boils at 80·5° C. Acute benzene poisoning, which plays an important part as an industrial poisoning, is caused by inhalation of benzene fumes. The various kinds of benzol used commercially contain, besides benzene, alkyl benzenes, especially _toluene_ (methylbenzene, C₆H₅.CH₃, boiling-point 111° C.); _xylene_ (dimethylbenzene, C₆H₄[CH₃]₂, boiling-point 140° C.); _pseudocumene_ and _mesitylene_ (tri-methylbenzene, C₆H₃[CH₃]₃, boiling-point 169° or 163° C.); the regular presence of _thiophene_ (C₄H₄S, boiling-point 84° C.) in commercial benzol must also be taken into account. Industrial benzol poisoning arises, therefore, as a rule, not from the action of pure benzene vapour, but from fumes which contain a mixture of the compounds mentioned.

The course run by industrial benzol poisoning is often very acute, if large quantities are inhaled—death occurring suddenly, after a short illness with symptoms of vertigo. Gradual inhalation of lesser quantities gives rise to headache, giddiness, malaise, then twitchings appear which develop into convulsions, and lastly unconsciousness. In order to ascertain in what manner the various substances contained in commercial benzol share in the poisonous effect, experimental research seemed to me to be indispensable, especially as published statements so far gave no accurate data.

Two cases of industrial benzol poisoning have given rise to close experimental research upon the poisonous nature of benzene.

Lewin undertook experiments on animals; which he confined under bells and caused to inhale fumes of chemically pure and impure benzene. He mentions that even at comparatively low concentration poisoning results, and indeed more readily and certainly from the action of impure than pure benzene. Lewin found that when air was made to flow slowly first through benzene and then into the bell, symptoms of paralysis, convulsions, and unconsciousness showed themselves in from four to six minutes. After-effects by this means could not be observed. Lewin maintains, however, that in man even slight acute action of benzene can be followed by after-effects (giddiness, sickness, headache, distress in breathing, and oppression of the heart).

Santesson made researches upon the poisonous action of benzene in connection with occurrence of certain cases of poisoning through ‘impure benzol’ (coal-tar benzene) in a rubber tyre factory. In the factory mentioned nine young women were poisoned, of whom four died. The symptoms shown were lassitude, anæmia, giddiness, headache, vomiting, and fever. Post mortem, hæmorrhages and fatty degeneration of the endothelium of the bloodvessels and various organs were found. Experimental research showed that commercial benzol and chemically pure benzene had the same effect. Santesson did not succeed in his experiments on animals in producing chronic poisoning by inhalation of benzine and of benzene fumes (which two completely different poisons he does not distinguish strictly from each other, as is the case, unfortunately, with many other writers). My experimental researches upon the poisonous effect of pure benzene, pure toluene, cumene, thiophene, and the most important kinds of commercial benzol gave the following results:

For rabbits the limit of toxicity is a proportion of 0·015 to 0·016 per thousand pure benzene in the air, that is 0·015 to 0·016 c.c. benzene vapour per litre of air.

A concentration of 0·056-0·057 per thousand pure benzene in the air causes in rabbits at once—after one minute—twitching of the muscles; after eight minutes, convulsions; after ten minutes, deep narcosis; and after twenty-five minutes, coma. If the animal is taken out of the bell in time, even if it has shown marked symptoms, it recovers very quickly (in two to ten minutes) without manifesting any after effects. Even in animals repeatedly exposed to the poison sequelæ were not observed.

Dogs are somewhat more susceptible to pure benzene than rabbits; 0·024 per thousand causes after ten minutes severe convulsions, which after twenty minutes become continuous; 0·042 per thousand kills after twenty minutes (sudden death in a state of tetanus).

Cats are less sensitive than dogs and more sensitive than rabbits; 0·03-0·04 per thousand causes after ten minutes attacks of cramp and, after twenty minutes, convulsions; 0·05 per thousand at once brings on poisoning symptoms. As regards the character of the symptoms (cramps, convulsions, quick recovery, no after effects) the above statements apply to all three kinds of animals (rabbit, dog, and cat).

Chloral hydrate completely checks the convulsions and enables animals to tolerate higher concentrations of benzene for a longer time.

Benzene is thus to be counted among nerve irritant poisons. The convulsions are probably provoked by excitement of the motor centres in the brain.

In view of the fact that thiophene in a concentration of 0·03-0·05 per thousand in the air was borne by animals for an hour without producing any symptoms of poisoning, the proportion of thiophene in commercial benzol must be looked upon as practically non-injurious.

The so-called 90 _benzol_—a commercial benzol of which 90 per cent. distils at 100° C.—has naturally a somewhat weaker action, although, in respect of the poisoning symptoms produced, it is similar to that of pure benzene.

_Pure toluene_ (boiling-point 111° C.) and purified toluol (commercial product, boiling-point 109°-112° C.) produce, when inhaled, gradually increasing narcosis in the three kinds of animals referred to; they produce no symptoms of convulsions or spasms.

After the animals have been taken out of the bell, recovery is not so rapid as after benzine inhalation, but takes from half an hour to one hour. In rabbits and cats 0·046-0·05 per thousand produces after fifteen minutes staggering and paresis; after thirty minutes deep narcosis. The dog is again somewhat more susceptible, as little as 0·034 per thousand causing these symptoms in the same time.

‘Purified toluol’ (commercial product) acts somewhat less rapidly than pure toluene, but this small difference in effect need hardly be considered.

Other poisons were also investigated:—

_Solvent naphtha I_, a commercial product, of which 90 per cent. comes over at 160° C.; it contains little toluene, chiefly xylene, pseudocumene, and cumene.

_Solvent naphtha II_, of which 90 per cent. comes over at 175° C, it contains besides xylene, chiefly pseudocumene, mesitylene, cumene, &c.

The fumes of solvent naphtha I cause, when inhaled by rabbits, dogs, and cats, gradual narcosis, although not nearly so quickly as toluene at similar concentrations; recovery usually takes over an hour after the deeply narcotised animals have been removed from the bell. Rabbits and cats are affected in about equal degree. The dog is the more sensitive. Rabbits and cats can tolerate about 0·012-0·013 per thousand of the fumes of solvent naphtha I in the atmosphere for a long time without any symptoms. Only after breathing for fifty minutes air containing 0·0536 per thousand do they become narcotised. In the dog 0·036 per thousand causes narcosis only after thirty minutes.

With the fumes of solvent naphtha II I could not affect rabbits at all. The cat also, in spite of long inhalation of the heavy fumes, showed no marked symptoms of poisoning. In the dog gradual narcosis came about only after an hour’s inhalation of 0·048 per thousand.

The fumes of pure _xylene_ caused narcosis in rabbits after forty minutes’ inhalation of 0·05 per thousand in the atmosphere; after being taken out of the bell the animals recovered slowly (after half an hour to one hour).

_Cumene_ causes no symptoms after one hour’s inhalation in a concentration of 0·06 to 0·07 per thousand. This explains the effects of solvent naphtha I (in which xylene preponderates) and solvent naphtha II (in which pseudocumene, cumene, &c., preponderate). After effects were not observed.

Benzol and toluol fumes, and particularly those of solvent naphtha, exercise a distinctly irritant effect upon the mucous membrane, which, however, passes off without after effects.

Pure benzene, therefore, proved the most poisonous of the substances under investigation. When inhaled its effect (convulsions, with quick recovery) differs essentially from that of toluene, solvent naphtha, xylene, and cumene (gradual narcosis, slow recovery). The fumes of the various kinds of commercial benzol (solvent naphtha) boiling at a higher temperature are practically non-poisonous (solvent naphtha II). Pure benzene fumes are, however poisonous, even in very small quantities in the air. The limit for animals lies at 0·015-0·016 per thousand.

Lehmann has shown in a recent work that man, exposed to a mixture of benzene and air, absorbs 80 per cent. of the benzene.

Treatment of acute industrial benzene poisoning consists in severe cases of artificial respiration, with simultaneous administration of oxygen; in slight cases it is sufficient to bring the patient into fresh air.

_Naphthalene._—Naphthalene, which is insoluble in water, has irritant effect upon the mucous membrane and upon the skin when brought into contact with it.

Long continuance in an atmosphere containing naphthalene as dust or fumes causes headache, nausea, giddiness, &c.

HALOGEN SUBSTITUTION PRODUCTS

ALIPHATIC SERIES (NARCOTIC POISONS)

The halogen substitution products of the aliphatic series are not of much account as industrial poisons. They have generally a narcotic effect, that is, a paralysing effect upon the central nervous system, usually preceded by a short stage of excitement. This effect shows itself typically on inhalation of chloroform (methanetrichloride, CHCl₃), which however plays no part as an industrial poison. The narcotic effect of the other alkyl chlorides is less than that of chloroform. With carbon tetrachloride (CCl₄) the narcotic effect is only half that of chloroform; it causes, however, a more violent excitation; inhaling the fumes brings on nausea, coughing, sickness, headache, &c.

_Methylchloride_ (CH₃Cl) has a less narcotising effect. On the other hand it has a stronger local irritant action, which is indeed present also in chloroform, though not so apparent. This gas, as is well known, is used as a local anæsthetic in medicine.

Pure _methylene chloride_ (CH₂Cl₂) similarly is much less powerful than chloroform. Severe poisoning, alleged to have resulted from methylene chloride was caused by a mixture, called indeed methylene chloride, but composed of methylalcohol and chloroform.

Of the remaining halogen substitution products of methane, _methyl bromide_ (CH₃Br) and _methyl iodide_ (CH₃I) have given rise to industrial poisoning.

These poisons also act in the same way as the alkyl chlorides, but the excitement accompanying the narcosis is more marked—so far as the scanty observations allow conclusions to be drawn. The symptoms first show themselves in sickness, giddiness, hebetude, slowing of respiratory movements and of the heart’s action; convulsions or delirium ensue.

Treatment consists in artificial respiration or promotion of breathing by a plentiful supply of fresh air or oxygen; in pronounced narcosis stimulating remedies should be applied.

BENZENE SERIES

_Chlorobenzene_, and _nitro-_ and _dinitro-chlorobenzene_ and _benzoylchloride_, have given rise to industrial poisoning.

To chlorobenzene similar action is attributed as to benzene (headache, fainting, rapid breathing, cyanosis); changes in the blood (methæmoglobin formation) have also been observed.

Nitro- and dinitro-chlorobenzene are active poisons; the effect corresponds in general to that of nitro- and dinitrobenzene, but in addition the fumes or dust have markedly irritant action on the skin (dermatitis).

_Benzoylchloride_ (C₆H₅COCl), a colourless, pungent-smelling liquid, produces a violently irritant effect upon the mucous membrane, decomposing into hydrochloric acid and benzoic acid.

Treatment is analogous to that of benzene poisoning, and in cases of benzoyl chloride poisoning to that by hydrochloric acid.

It may be mentioned that chlorine rash is attributed to the action of chlorinated tar products (chlorobenzene compounds).

HYDROXYL SUBSTITUTION PRODUCTS

FATTY SERIES (ALCOHOLS)

The hydroxyl substitution products of the fatty series belong mainly to the narcotic poisons; the greater the molecular weight of the alcohol, the more marked is usually the narcotic effect. According to this propylalcohol is eighteen times as poisonous as ethylalcohol; butylalcohol and amylalcohol have from 36 to 120 times as great a narcotic effect as methylalcohol.

_Methylalcohol_ (wood spirit, CH₃OH) plays relatively the greatest part among alcohols as an industrial poison, because it is employed as a means of denaturing spirit. Its poisonous nature is relatively great, being very persistent. Industrial poisoning by methylalcohol is due to inhalation of the vapour and is rarely of a severe nature. The fumes have a strongly irritant effect upon the mucous membrane, giving rise to throat irritation, cough, hoarseness, and in severe cases bronchitis and inflammation of the conjunctiva of the eye. In addition inhalation of methylalcohol vapour causes headache, giddiness, nausea (inclination to vomit), and occasionally also twitchings and tremor.

The _higher alcohols_ (propyl-, butyl-, amyl-alcohol, C₃H₇.OH, C₄H₉.OH, and C₅H₁₁.OH) occur in fusel oil. They cause but slight (if any) industrial poisoning. Cases of more severe industrial poisoning through amylalcohol fumes have been described (in factories for smokeless powder), with symptoms of sickness, headache, giddiness, with fatal issue in some cases, preceded by severe nervous symptoms (convulsions or delirium).

Beyond speedy removal out of the dangerous atmosphere, probably no special treatment is needed in these cases of industrial poisoning from alcoholic vapour.

_GROUP: NITRO AND AMIDO COMPOUNDS OF THE ALIPHATIC AND AROMATIC SERIES (BLOOD POISONS WHICH FORM METHÆMOGLOBIN)_

Characteristic of the nitro and amido compounds of the aliphatic and aromatic series of the organic substances is their action upon the blood. The normal oxyhæmoglobin (blood-colouring matter) is changed into methæmoglobin, with which the oxygen is so firmly combined that the internal exchange of gases necessary to life becomes impossible. Methæmoglobin has a dark chocolate-brown colour and a clearly defined characteristic spectrum.

Of the poisons belonging to this group several are important. In so far as these substances are volatile—and this is generally the case with those causing industrial poisoning—effects are due to inhalation of fumes, but it is proved that the poisons of this group in liquid form can be absorbed by the intact skin, and this channel of absorption is characteristic of industrial poisoning. Severe poisoning results especially from wetting the skin by spilling on the clothes, &c.

The grey-blue discoloration of the mucous membrane, especially of the lips, is characteristic; sometimes also the skin is altered in colour. This discoloration is often noticed by others before the patient feels unwell. Soon the person affected has general nausea, vomiting, headache, giddiness, severe nervous symptoms, feeling of anxiety, and difficulty of breathing; in severe cases unconsciousness comes on, and death occurs with increasing cyanosis (lividity).

Treatment is naturally that which has been emphasised in the introductory words to Part II, which hold for all blood poisonings. In mild cases oxygen treatment has given good results. In all factories where such poisoning can occur provision should be made for immediate oxygen treatment. Besides this, the workers must be adequately instructed as to the danger and symptoms of poisoning, especially of the characteristic premonitory skin discoloration, in order to be able to assist their fellows.

NITROCOMPOUNDS

ALIPHATIC SERIES

_Nitro-glycerin_ (triple nitric acid ester of glycerin, C₃H₅.[NO₃]₃), the well-known oily explosive liquid, has also an irritant local effect. When absorbed into the body, in addition to methæmoglobin formation, it causes dilatation of the bloodvessels, slowing of the respiration and heart’s action, and attacks of suffocation. The general remarks upon this group apply here, but symptoms referable to central paralysis occur as the methæmoglobin formation is slow. Industrial poisoning arises through inhalation of gases containing nitro-glycerin and also by absorption through the skin. Statements as to its poisonous nature are very varied. Under certain conditions moistening the skin with small quantities of nitro-glycerin suffices to produce symptoms. Probably the susceptibility of different persons varies greatly.

_Amylnitrite_ (nitric acid amyl ester, C₅H₁₁NO₂), a characteristically smelling liquid, acts similarly. The fumes of amylnitrite, even when inhaled in small quantities, cause marked dilatation of the bloodvessels, through paralysis of the muscular walls of the bloodvessels, thus causing marked flushing of the face; the pulse becomes quick, then weak and slow.

NITRO AND AMIDO COMPOUNDS

AROMATIC SERIES

The substances of this group are important.

_Nitrobenzene_ (C₆H₅NO₂, named oil of mirbane), a yellowish liquid of characteristic smell, induces especially the formation of methæmoglobin in the blood; the effect upon the central nervous system (first excitation, then depression) is often absent. The description of the disease in general in the introductory words of this whole group is characteristic. Occasionally signs of asphyxia show themselves; sometimes there are twitchings, disturbance of the power of sensation, and convulsions; early discoloration of the mucous membrane and the skin, which assume a blue to grey-black colour, is characteristic.

Chronic poisoning is also attributed to nitrobenzene, showing itself in lassitude, headache, malaise, giddiness, and other disturbances of the nervous system.

_Nitrotoluene_ (C₆H₄CH₃NO₂), of which the ortho-compound acts most powerfully, and also _nitroxylene_ (C₆H₃[CH₃]₂NO₂) have similar but less marked effect.

The _dinitrobenzenes_ (C₆H₄[NO₂]₂) are stable bodies. Meta-dinitrobenzene inhaled as dust or otherwise, can produce marked poisoning symptoms essentially the same as those described. Especially characteristic is the early dark discoloration of the skin.

Symptoms resembling nitrobenzene poisoning in general are caused by _nitrophenols_ (C₆H₄.OH.NO₂), of which paranitrophenol is the most toxic; also by _dinitrophenols_ (C₆H₃[NO₂]₂OH), solid crystalline substances which melt at different temperatures, and the _mono-_ and _di-nitrochlorobenzenes_ (C₆H₄.Cl.NO₂ and C₆H₃.Cl[NO₂]₂). In cases of industrial poisoning by dinitrophenol, observed by Leymann, the workers were taken suddenly ill, with symptoms of collapse, pains in the chest, vomiting, distress of breathing, rapid pulse, and convulsions, and died within a few hours. At the autopsy a yellow substance was found with picric acid reaction which appeared to be di- or tri-nitrophenol. In other cases, some fatal, of industrial nitrochlorobenzene poisoning, also observed by Leymann, the typical grey-blue discoloration of the skin was obvious, and the chocolate-brown colour of the blood produced by methæmoglobin.

_Trinitrophenol_ (picric acid, C₆H₂[NO₂]₃OH) is a yellow crystalline compound with bitter taste; poisoning by this substance exhibits clearly strong local irritant action (upon skin, mucous membrane, and intestinal canal, and especially upon the kidneys), besides effect on the blood and central nervous system. Prolonged action of picric acid upon the skin causes inflammation. Absorption of picric acid dust causes inflammation of the mucous membrane of the respiratory passages and symptoms of gastric and intestinal catarrh as well as inflammation of the kidneys.

A jaundice-like discoloration of the skin and darkening of the urine are also characteristic; sometimes picric acid poisoning produces a rash resembling that of measles and scarlet fever.

_Nitronaphthalene_ (C₁₀H₇[NO₂]) and _nitronaphthol_ (C₁₀H₆.NO₂.OH) in addition to methæmoglobin formation have an irritant action. It is stated also that dulness of the cornea is produced.

_Azobenzenes_ also, which are to be considered as intermediate between nitrobenzene and aniline, form methæmoglobin (azobenzene, C₆H₅N = NH₅C₆).

_Aniline_ (amidobenzene, C₆H₅.NH₂), a colourless, oily liquid of aromatic smell, has only slight local irritant effect. In the frequent cases of industrial poisoning by ‘aniline oil’ or aniline hydrochloride, in which the aniline enters through the skin or is inhaled in the form of fume, there appear the typical symptoms common to this group, of the action upon the blood through methæmoglobin formation: headache, weakness, cyanosis, difficulty in breathing, &c., to which are added nervous symptoms such as convulsions and psychical disturbance, although these play a subordinate part in industrial poisoning. In severe cases the typical symptoms of air hunger are shown. Occasionally recovery only takes place gradually, and signs of irritation of the kidneys and inflammation of the urinary organs are seen. These symptoms occur only rarely in acute industrial poisoning, but are, however, in so far worthy of notice because of the frequent occurrence of tumours in the bladder among aniline workers. It is possible that here the irritant action of the urine which contains aniline plays a part. The tumours in the bladder operated upon, in some cases with success, were many of them non-malignant (papillomata), but some were carcinomata (cancerous new growths) running a malignant course, and recurring after operation. In the urine the aniline combines with sulphuric acid, and is partly excreted as paramidophenol sulphuric acid.

The treatment of aniline poisoning is the same as that for all the poisons of this group. In view of the occurrence of tumours of the bladder in aniline workers, they should be instructed to seek medical aid on the first indications of trouble, so that a careful cystoscopic examination may be made.

_Toluidine_ (C₆H₄.CH₃.NH₂), which is mixed with aniline for industrial use, produces the same symptoms with marked irritation of the renal organs.

Of the _nitroanilines_ (C₆H₄.NH₂.NO₂) _paranitroaniline_ is the most poisonous. Characteristic of the action of this compound is methæmoglobin formation, central paralysis and paralysis of the heart’s action.

Of the _benzenediamines_, _paraphenylene diamine_ (C₆H₄[NH₂]₂) may be regarded as an industrial poison. The irritant action of this substance is prominent; it induces skin affections, inflammation of the mucous membranes, more especially of the respiratory organs, and sometimes inflammation of the kidneys. They have been noted in workers using ursol as a dye; here, doubtless, the action of diimine (C₆H₄.NH.NH.) must be taken into account, which arises as an intermediate product and exercises a markedly irritant action. Further, the general effect of paraphenylene diamine is an irritant one upon the central nervous system.

_APPENDIX_

TURPENTINE, PYRIDINE BASES, ALKALOIDS

_Turpentine oil._.—Turpentine oil is a peculiar-smelling, colourless liquid of the composition C₁₀H₁₆; different reactions show that turpentine oil contains the aromatic nucleus (cymene). It is used in the manufacture of varnish, and thus can cause industrial poisoning by inhalation of fumes. Even from 3 to 4 mg. of vapour of turpentine oil per litre of air brings on severe symptoms. Turpentine oil acts as a local irritant, and when absorbed into the system has an exciting effect upon the central nervous system. Inhalation of large quantities of turpentine vapour cause rapid breathing, palpitation, giddiness, stupor, convulsions, and other nervous disturbances, pains in the chest, bronchitis, and inflammation of the kidneys. The last-mentioned symptom also arises from the chronic action of turpentine vapours.

_Pyridine._—Pyridine (C₅H₅N), a colourless liquid of peculiar odour, is employed as well as methylalcohol in denaturing alcohol. The disturbance of health observed in workers occupied with the denatured spirit are probably mainly due to the inhalation of fumes of methylalcohol. Pyridine is comparatively innocuous. Eczema, from which persons suffer who come into contact with denatured spirit, is ascribed to the action of pyridine. Larger doses produce a paralysing effect, but this need not be considered in its industrial use.

_Nicotine, tobacco._—According to various published statements, effects among tobacco factory workers are attributed to the nicotine contained in tobacco dust and to the aroma which fills the air. Nicotine in large doses has at first an exciting followed by a paralysing effect upon the central nervous system; it causes moreover contraction of the unstriped muscles and has a local irritant effect.

The symptoms of illness ascribed to nicotine are: conjunctivitis, catarrh of the air passages, palpitation, headache, want of appetite, and, particularly, tendency to abortion and excessive menstruation. Severe industrial poisoning due to nicotine has only been observed in workers who chewed tobacco leaves.

_Poisonous wood._—The symptoms of disease noticed in workers who manipulate certain kinds of wood are attributed by some writers to the presence of alkaloids. Such knowledge as we have of the illness due to them—they are evidently of the nature of poisoning—is referred to at the end of Part I.