Document 99qpRvQQx4xw2DNzKvgN6kLK7

TOXICITY OF INDUSTRIAL METALS SECOND EDITION ETHEL BROWNING, M.D. formerly H.M. Medical Inspector of Factories; Adviser on Toxicology to the Courlauhi Organization 1969 NEW YORK appleton-century-crofts Division of cdilh Corporation LONDON BUTTBRWORTHS 40 TOXICITY OF INDUSTRIAL METALS reverberatory furnace, with small amounts of iron pyrites or galena. When cooled by passage through a scries of brick chambers, the oxide condenses as a crude product to be puriikd by re-sublimation (Buchanan, 1961). Arsenic can also be prepared from inispickcl by heating in earthenware retorts and distilling off the arsenic condensed on sheet iron in the neck of the rctorL It can also be obtained, free from oxide, by reducing pure As,Ok with zirconium. PROPERTIES In its stable form arsenic is a steel-gray, brittle, crystalline metalloid. It exhibits allotropy, the two other forms usually distinguished being yellow and black respectively. It forms three oxides--the trioxidc, As.O, (the most abundant commercial source of arsenical compounds); the pcnloxidc, As,Ot (the primary materia) for many arsenical insecticides); and the tetroxide, AsjO,. Atomic number, 18; atomic weight, 14-91; specific gravity, 5-73 (yellow allotrope 3-7, black ailoiropc 4-7 ; threshold limit value O S mg. per c.m.). PROPERTIES OF ARSENIC TRIOXIDE (THE PRINCIPAL COMPOUND) The crude arsenic trioxide dust obtained by sublimation during smelting of arsenic-containing ores consists of approximately 97 per cent of AS|0,, Us principal impurity being antimony trioxidc. Pinto and McGill (1953) stated that the particle size of over 23 per cent of the dust is over S-Sp. It is only slightly soluble iu water but soluble in alkaline and acid solutions. It was stated by Schwartze (1922) that the toxicity of arsenic trioxidc was inversely proportional to die particle size, the oral L.D.U for the rat varying between 75 and 500 mg. of arsenic per kg. according to Ihe sip. Ollier inorganic compounds of arsenic include arsenic chloride, (" butter of arsenic *'), a colourless oily liquid used chiefly in the manufacture of pharma* ccuticals; arsenites, arsenates and sulphur compounds. Die arsenite salts in which the acid corresponds to arsenious und arsenic acids, while of the alkali salts, sodium meta-arsenate, which is readily soluble in water, is the most widely used. Of the arsenates, those of lead, calcium and magnesium are mainly used as spray insecticides, and in recent years magnesium arsenate has been found of value in Hie manufacture of lluoresccnl lamps. Tlw sulphur compounds, As.S, (orpimcnl) and realgar (As.O,) have been largely supplanted as pigments by Wad chromes, and as a depilatory rcalgarjias been generally replaced by sodium sulphide. Arsenical pigments--copper arsenile (Selicelc's Green) and copper uccto arsenite (Scliwcinfurlc Green) were formerly widely used as pigments in wall paper, calico printing and as wood preservatives, but their use for these pur poses is now much diminished, partly on account of lltc liberation of llie toxic gas dimethyl arsine by the action of moulds. Organic compounds of arsenic,--The ursphcnumincs--Salvnrsan and Ncosalvarsnn--derived from diarscnobcnzenc, arc best known for their therapeutic effects ip protozoal diseases, which were first demonstrated ARSENIC AND ARSINE 41 following the discovery that atoxyl (sodium nrsenilatc) had this projicrty, but they have now been largely supplanted by antibiotics. ESTIMATION OF ARSENIC In estimating trace amounts of arsenic in biological or industrial material, it must be rendered soluble. Diereaftcr, there are several very well-known chemical tests--Rcinsch, Marsh and GuUeit--dcscribcd in detail in standard works on analytical chemistry, and more concisely by Buchanan (1961). Estimation by radionctivation was fust described by Smales and Fate (1952) and adapted by Lenihan nnd Smith (1958). The sample to be irradialeJ is placed in an atomic pile, then converted into arsine, which is absorbed in a solution of mercury chloride and examined by a Geiger counter. Estimation by neutron activation analysis is described by Krishnan, S. S. el ai. (1966). INDUSTRIAL USES Arsenic is used industrially for the following purposes. (1) In the manufacture of insecticides, weed killers and fungicides (usually in Ihe form of potassium arsenite), and as a wood preservative. (2) In glass manufacture as a bronzing or decolorizing addition, and in the production of opal glass and enamels, particularly in the majolica industry in Italy (Dcchigi, 1936). (3) As an addition to alloys in amounts of 0-3-0-5 per cent to increase hardening and heat resistance. (4) In the manufacture of arsenical organic compounds for tlierapeutic use. MAXIMUM ALLOWABLE CONCENTRATION Tlie MAC recommended by the American Conference of Governmental Industrial Hygienists in 1962 and not since revised is as follows: Arsenic (dust) mg. pcrc,m. Arsine 0 05 p.p.m. (0-2 mg. per c.m.). METABOLISM Although arsenic is not an essential element of human metabolism, it is, owing to its wide distribution in nature, constantly taken into the hitman body in very small quantities, and is therefore regarded by most authorities as a normal constituent of tlie body. Following the publication of a series of papers by Gautier (1899), claiming lliat amounts varying from 0113 lo 0-76 mg. per 100 g. were present in the normal mammary glands, thyroid gland, thymus gland, hair, skin and bones, und tho denial of lids claim by a Committee of the French Academy, wide controversy was aroused, particularly from the medico-legal experts, hut a9 Ihe result of a large series of examinations by Myers and Cornwall (1925) it appeart to be generally agreed that such small amounts as those postulated by Gautier can be regarded us " normal **. According to Cluster (1931) 42 TOXICITY OP INDUSTRIAL METALS " (races of arsenic less than one part per S million parts of viscera should bo red ", DISTRIBUTION AND STORAGE OF ABSORBED ARSENIC About four-liftIvs of tiro umount of arsenic absorbed is stored and widely distributed in the tissues, including the liver, abdominal viscera, bone, skin. and particularly the Imir ami nails, where >1 may be ilctcclcd many months after it lias disappeared from the urine aud faeces. Determination of Hie rule ot absorption of arsenic has been facilitated by Ute modern use of radioactive tracers. By exposing tire hair to a flux of thermal neutrons, the arsenic Is rendered radioactive, and its localization, as a fraction of length of the hair determined (Griffon and Darbaud, 1951). Arsenic was found in the hair in considerable amount in chemical workers manufacturing a solution of sodium arsenite (Hill and Faniag, 1943)--108, 35 and 64 p.p.m. in 3 categories of exposed persons as compared with 13 p.p.m. in controls. Goldblatt and Goldblatt (1956) suggested that" a kind of equilibrium is readied la the hair which is independent of the amount of arsenic passing through tire body as indicated by the markedly different urinary excretion In a case of subacute poisoning of several weeks* duration, Heyndrickx (1955) found the greatest amount of arsenic in the proximal 5 cm. and from one-tenth to one-twentieth less in the more distal parts of die hair, a finding which be considered to suggest that the duration of the intake had been longer than the ease history indicated. The blood of normal women, according to Guthmann and Grass (1933), contains 20-100 pg. of arsenic per 100 g., and since they found a consider able increase during menstruation and the early months of pregnancy, they concluded that arsenic seems to have a direct relationship to growing tissue end cell proliferation. In women with carcinoma there was an average Increase of 43 per cent oyer that of Hie liitermcnstruni normal value. In rail, about 80 per cent of the arsenic in the blood is concentrated in Die red corpuscles. Cows' milk contains amounts of arsenic varying between 32 and 60pg. per L. (1 (overt/., 1938), EXCRETION Arsenic Is excreted slowly, some appearing In the urine and, to a smaller extent, in the faeces within 24 hours, but a large proportion of die amount absorbed is stored in the tissues and eliminated at varying intervals of time. The normal value of urinary arsenic for persons with no known exposure has been variously calculated as 0 014 mg. per L. (Webster, 1941); 0 017 mg. of As,0, per 100 ml. (Watrous and McCaughcy, 1945); and 0-13 mg. per L. (Pinto and McGill, 1953). According to Grolbiian 0958) there is practically no difference In live urinary arsenic content of adults and children. . The urinary arsenic of workers exposed to arsenic may show much higher values than non-exnosed persons Pinto and McGill found levels of an average of 0-82 mg. per L. as compared with 0-13 for live controls, but stated that evidence ofsystemic poisoning is rare even with a level of4-5 mg. ARSENIC AND ARSINE 43 per L., indicating that much more arsenic can go lltrough the human body without causing illness than has been previously realized, Oreslnno and Abbutc (1937) believe that tiro amount of arsenic eliminated in the urine is independent of live dose so tong as this is tolerated. With regard to lead arsenate, it appears front the investigations of Fnirliall rt /. (1938, 1941,1943) Itial lids compound is broken down in the body with subsequent excretion of most of the urscnic by the kidney, and according to Gcrin (1957) tire arsenic disappears from the urine more rapidly Ilian the lead. Fairliall's findings indicated furthermore that in the presence of lead, arsenic is eliminated more intensively and that the arsenate radical either decreases the absorption or increases the excretion of lead while soluble arsenates decrease the lead storage. TOXICOLOGY In acute poisoning arsenic is a general protoplasmic poison acting upon various ferment processes, especially live phosphatases (Oclkers, 1937), leading to diminished oxidation and tissue respiration. It has also a paralytic action on smooth muscle and thus acts as a vascular poison, leading to haemorrhage (Nonnenbruch et at., 1936). In the cell, the toxic effect is exerted on the chromosomes, particularly--according to Bucher (1940)--as a blockage of the mitotic metaphase, a property which it shares with colchicum. It is believed by some authorities tiiat the immediate effects on tlie gastro-inlestinai mucous membrane are due to increased per meability of the capillaries. In industry, acute poisoning from solid arsenic is rare ; subacute and chronic poisoning usually arises from exposure to arsenic-containing dust and fume. The most dangerous arsenical compound, not used as suclv but occiirrimt ns the result of accident, is arsine, or hydrogen arsenite, a powerful haemolytic agent. ARSENICAL POISONING IN ANIMALS Acute.--A wide variation of toxicity has been reported in various animal species and even in strains of the same species; both the particle size and tlie amount of impurity have been found to inllucncc the L.D. ,, dose. From the investigations of Harrison clitl. (1958) it appears that the strain variation is less marked ip the mouse than in other animals. They also found that solutions of arsenic trioxide are many times more toxic than the dry powder, and that the high purity compound was less irritant to the gastro-inlestinai tract than tlie crude sample, possibly on account of tlie presence of impurities such as antimony. Gastro-inteslinal damage, as evidenced by severe con vulsions and retching, and hacmorrluigc of the stomach and intestines was a marked feature of the crude arsenic trioxide, while the pure preparation caused much less discomfort and only slight reddening of the gastric mucosa. Ilio ultimato L.I). Il( however, was less for the pure than the crude prepara tion (39-4 mg. of arsenic per kg. as compared with 42 9). In the liver, fatty degeneration, cell necrosis and reparative changes following acute injury by arsenic have been observed (Kiissing, 1941). 46 TOXICITY OF INDUSTRIAL MFTAIS Arsenic trichloride (AsCl,) u liquid evaporating with emission of dense while fumes, causes u severe conjunctival reaction with el lemosis and neerolic conical lesions (Ulule, 19'16). (r) Anine. In a case renoiled by Oernchl, Stead and Natt (19-1'!), intense irritation of the eves, with nalncbial oedema, occurred in a inelal relincry ~ where fume was accidentally generated. Arsine was thought to be the most, active agent but slibine and sulphur hydrides were also present. ,. (,/) Organic Anenlaih. The extreme tonicity to lire eyes ofsome Irivalent organic compounds is due, according to Duke Older (1954) to their rapid linkage with lire su!|diydryl groups In proteins and enzymes essential for carbohydrate metabolism, a view also held by Dixon and Needham (1946). The most virulent is Lewisite (chiorovinyIdiddoioarsine), once intended but not used for chemical warfare. Cluronic.--The chronic symptoms observed in workers exposed to arsenic and its compounds arc related chiefly to the skin, mucous membranes, gaslro-intcslinal and nervous systems, and in a few cases disorders of the circulatory system and the liver have been recorded. German observers have described many of these manifestations from the use of arsenic as an insecticide, particularly in wine dressers (Dorle and Ziegler, 19JO; (Schorndorff, 193S; von Pein, 1940;'von Petn and Baurhcnn, 1943) though it has been suggested that the arsenic poisoning of wine dressers is not due so much to inhalation or skin contact, but as the result of ingestion of contaminated wine. The question of a potential carcinogenic action of arsenic on organs other than the skin has been much debated. `Flic recorded cases of carcinoma of the lung, larynx, viscera, and multiple tumours of the skin or viscera, or both, associated with chronic absorption of arsenic are strongly suggestive of such a relationship, but some " adjuvant factor " in the metabolism or hormone balance of the sufferer or in the susceptibility of lltc affected tissues appears to be also concerned. SYMPTOMS OF CHRONIC INDUSTRIAL POISONING SKIN LESIONS Lesions of the skin in association with industrial exposure to arsenic were described as long ago as 1728 by Hcnckcl (Ihe so-called Niitlcn-Krittze). During the nineteenth century many cases of erythematous, puslular, or even ulcerative or gangrenous lesions were described, chtclly from Ilie manufacture or use of Sehweinfurlcr Green but also of oilier ursenlcal materials. Vigne (1930), describing the cutaneous lesions occurring during the manu facture of insecticides, considered that the most hazardous compounds in this respect were arsenic Irioxide and Paris Green; sodium arsenile, however, has also been found potent in producing skin lesions of very varied character. Lconcini (1933) described ulceration of the hands and feet, scrotum and perineum from its use ns a vermin killer, and Tumponi (1935) reported erythema, papules and ulcerations from its use as an insecticide. The inorganic arsenical compounds have been regarded by Ihc majority of observers as primary cutaneous irritants, not sensitizers. Schwartz et al. ARSENIC AND ARSINE 47 (1947) classified arsenic disulphide, sodium arsenale and arsenile and potassium arsenale as primary inilanis, but ulso designated arsenical com pounds in general us " Ihc ptincipal sensitizers met with in industry", llolmquist (1951), while unable to express an opinion on the sensitising capacity of every individual inorganic arsenical compound, found that the trioxide and penIoxide were dclmilely able to produce sensitivity; he con sidered that this capacity was sliared to a large extent by oilier compounds of arsenic, Ihc sensitization being dependent to some degree on the intensity of the exposure. The question as to whether inorganic arsenical compounds can produce sensitivity to organic compounds has been discussed by Jones (1940). On the basis of two cases--workers in an arsenic mine, who showed skin reactions 11 years later following an injection of neoarsphenamine--Jones suggested that previous industrial poisoning may provide Ihc mechanism for later sensitization to organic arscnicals. Nature of (lie skiu lesions.--Acute and subacute dermatitis is more common than the chronic or subchronic types. In the initial stages, which may arise in less than a week or only after years of employment, erythema, associated with burning and itching, is sometimes most intense around Ihc follicles, giving tlte skin a spotted appearance; when occurring on the face, accom panied by swelling, this may disappear without further development or may be followed by papular and vesicular eruptions. Puslular folliculitis may be accompanied by marked serous discharge, especially in areas exposed to rubbing or chafing, resulting in the forination of crusts. In some cases these lesions lical within a week leaving only slight pigmentation and desquamation; in others the skin becomes lichendied and liable to form new foci of inflammation even after cessation of exposure. In the cases described in great detail by IJolmquist (1951) where the exposure was related to the metallurgical working of copper ore in smelting works in Sweden, the dermatitis was mainly localized to the areas of greatest exposure--the face, neck, forearms, wrists and hands. It also occurred on the scrotum and thighs, the upper part of the chest and back and the lower legs. Recurrences in employees removed to departments with a lesser risk of exposure to arsenic suggested that sonic of the lesions were due to sensi tization; this was supported by Ihc results of patch tests, in which eczema tous readions were produced by arsenical compounds. A less acute but very prominent feature of skin lesions due to arsenic is hyperkeratosis, often accompanied by hypcihidrosis, especially of the palms and soles. Under the name hyperkeratosis, Watrous and McCuughey (1945) included cracking skin, thickness and dryness of skin, and warts. A diJl'iise branny desquamation of the skin of the trunk and extremities with dark, deeply pigmented ureas lias also been described (Hoynun et at., 1956) and has been likened to that of Addison's disease. A case of arsenical melanosis in a glass worker who also suffered from silicosis was described by Gi(jc (1951). In some areas the pigmentation alternated with dcpigmentalion ("rain-drop" pigmentation); in others, especially the hands and feet, it showed a striped appearance. It was assumed that the inhaled silica-containing dust also contained arsenic. The 48 TOXICITY OF INDUSTRIAL METALS nature and causation of lltc melanosis lias been investigated by several observers dating from Wyss (1890) and Gaits (1915) onwards. Osborne (1925), summarizing Ins own findings and comparing them with those of the earlier observers, with whom he agreed on the whole, concluded that the pigment contained no arsenic but lipoids and melanin derived from cell metabolism, not from the " products of brokendown blood ", and that it arose chiefly in the corium and to a lesser extent in tire epidermis, by an indirect action of arsenic on the mother substance of melanin. lluchanan (1961) remarks that melanosis is' certainly an indication of systemic absorption of arsenic, generally over a lengthy period, and not lltc result oflocal action. The anils.--The presence of whito striae in tire fingernails, described by Mecs (1919) has came to be regarded as almost a diagnostic accompaniment of arsenical polyneuritis. Mees observed this broad white band on ail the fingernails of 3 cases of attempted murder or suicide by arsenic and stated that its presence in association with polyneuritis was confirmatory of the diagnosis of arsenical poisoning; it was still distinct long after the dis appearance of arsenic from the urine. In the eases of Heyman el al. (1956), all of those who had hod symptoms of arsenical intoxication for 6 weeks or more, showed this phenomenon; it was not present in 4 patients observed for less than that time. These authorities believe that an approximate estimation of the exposure to arsenic could be made from tire distance of tire lines from the base of the nail; but there was no evidence that the actual growth of the nail was retarded by arsenical neuropathy. In 1 patient the time of migration of the lines to the free edge of the nail was 5 months (the approximate time for the nail to grow from the matrix to the free edge in normal persons). Nevertheless, examination of 2 other patients with Meet' tines showed no arsenic in the hair or urine. Indicating that these bands are not pathognomonic of arsenical intoxication. Cancer of the skin.--'lltc association of arsenic with skin ameer was reported by Hulchinson~(l887), in relation to the internal administration of arsenic over long periods, and has been.confirmed by many authorities sintT `that lime, especially from T-owlcr's solution (Arlicliser and Krenten, 1950 _ and other arsenical medicmilI preparations (Son)liters and McManus, 1953). Skin cancer from external contact with nrscilie-containing substances in industry has been relatively rarely reported; Leitch and Kennawav (1922). Iliounh they had succeeded ill producing a typiealliniaiiums-ceH carcinun a in animals by the external application of potassium ursenile in alcohol, stated that only two instances were on record tip to that lime which could reasonably be attributed to employment with arsenic ; both were workmen denting widi * sltccp dip, I In the series of eases of skin cancer recorded by Sommers and McManus : (1951), most were associated with the medicinal use of arsenic; only 2 were occupational in origin. One of these had used lead arsenate during his work ns ini electropi:iter anil liml shown nniliHitiTkeralDscs of the hands for 5 years before biopsies of a lesion of the thumb showed hyperkeratosis and epithelial hy pcnilasia. Following amputation an invasive eiinlermohl careinuma"wa3 found to be present. ARSENIC AND ARSINE 49 Ncubancr (1947) collected 143 published cases of arsenical cpi11iclhnm following medical ton with arsenic for diseases of the skin (psoriasis was predominant) and other conditions. 'I'faT most conn non form was again Fowler's soluliun (potassium nrsenite 1 per ccnt~o1uil:iletf~as~~As7T~T~ Arsenic trioxide was also given us~pHls; Donovan's solution was a com bination of the lodiJes of arsenic am) mercury. Nature nf the carcinomatous lesions.--Among the vaiying types of _iir'ieltlcnl~caTTCCronire~stan7cpitliciioim developiiig on the site of keratoses(the ** Hutchinson type") is the commonest. The keralolic lesions may have existed for many years before limy begin to undergo malignant change to epithelioma, usually of the squamous type. Such lesions have also been recorded its developing in patches of psoriasis, and even in normal skin. The association of arsenic with multiple epithcliomatoscs, sometimes of basal-cell type and of a low-grade malignancy, and with a chronic " precanccrous dermatitis" (Bowen's disease), described by Bowen in 1912, is still under discussion by dermatologists. MUCOUS MEMBRANES Dermatitis of the face and eyelids is sometimes accompanied by con junctivitis, with redness, swelling and pain. Two eases of severe kerato conjunctivitis were described by Paufique and Bonainour (1946) following exposure to calcium arsenate as an insecticide. In one ease corneal anaesthesia was accompanied by a corneal ulcer. There may also be irrita tion of the nose and pharynx, causing acute or chronic rhinitis, and of (lie bronchia) passages. Perforation of the nasal septum was described by Davis (1917) and by Dunlap (1921) in workers employed in copper smelting. The actual perfora tion is in most cases preceded by slight epistaxis, some irritation of the nose, and the formation of crusts owing to the resultant obstruction to nasal breathing, pharyngitis and possibly low-grade laryngitis. The perforation develops from a white slightly elevated area about 5 mm. in diameter followed by necrosis on both sides of the septum, when the cartilage dis appears from dystrophy. It was suggested by Dunlap that the arscniccoitluining dust breathed into the nose and coming into contact with the moist membrane forms arsenious acid, which causes necrosis of the septal mucosa, and by Pinto and McGill (1953) who observed similar cases in their workers exposed to arsenic trioxide, that the large particles (over 5 5p) which form a substantial part of the dust, readily impinge on the septum. (ASTUO-INTEST1NAL DISTURBANCE True gastro-cnterilis is not a common occurrence in industrial cli tonic arsenical poisoning. Pinto and McGill (1953) found only one case among their workers witlt arsenic trioxide, but digestive disturbance, ns shown by nausea and vomiting, is occasionally reported. A case described by Maycis (1954) in which severe gasIro-inlestinnI symptoms were predominant was unusual in that it apparently remained undiagnosed for mure than 20 years in spile of numerous admissions to hospital for disorders suggestive of JO TOXICITY OP INDUSTRIAL METALS arsenical poisoning. Thu man's exposure lo arsenic in the form of Paris Green powder had been heavy mid included (he possibility of inhalation, Ingestion, and skin absorption. The gastru-lnlcsiinal disturbance began soon after ho started work, with acute colic and haemalemesis, lie was found to have a ponehutiug gastric ulcer which healed hut returned wlten lie resumed work and disappeared only when exposure ceased entirely. During his 20 years of more or less intermittent exposure lie had repealed attacks of exfoliative dermatitis; these also disappeared when exposure ceased but left permanent trophic skin changes with discoloration. Other symptoms characteristic of arsenical poisoning were also present--conjunctivitis, upper respiratory irritation and polyneuritis--and death was finally due to cardiovascular degeneration. j ! I j ' ; j < ; { PERIPHERAL NEURITIS The symptoms of peripheral neuritis following exposure to arsenical compounds in industry, though infrequent, are identical with those recorded as due to ingestion (Kelynock el a}., 1900) and others. Unlike the pcriphercl neuritis of lead poisoning, in which pain and disturbance of sensibility ore usually absent, arsenical polyneuritis is accompanied by pain, with burning and tenderness in the affected limbs, and difficulty in walking. These symptoms were present in the cases described by Heyman el at. (1956), 7 of which were said to be due to direct contact with arsenate sprays or dusts. Some of the cases had an initial stage in which the symptoms were those of acute poisoning--nausea, vomiting and diarrhoea--but in tlie 7 industrial workers the onset was gradual, with development of sensory disturbances in die extremities--numbness, tingling and " pins and needles "--followed by severe symmetrical weakness in the feet and legs. As in the cases described by Hassin (1930), high levels of arsenic were found in the hair and also in the urine--2-5 mg. per 100 g. in the hair, and 0T-6 mg. in a 24-hour speci men of urine. In Hassin's cases, where the source of the arsenical poisoning was not determined, the diagnosis was confirmed also by the presence of " Mces' lines " on the nails. ' The difficulty in distinguishing between the polyneuritis of lead poisoning and that of arsenic is emphasized by a case recorded by Barbier el at. (1942), The polyneuritic symptoms were at first diagnosed ns due lo lead poisoning, since tire man had used lead arsenate as an insecticide spray. The out standing feature of this cose was motor weakness of the hands and difficulty in walking; the diagnosis of arsenical polyneuritis rested chiefly on the evidence of an initial gastro-intcslinal disturbance and the presence of Mccs' bands on the nails; there was no hyperkeratosis and no tingling or numb ness of the hands and feet. f | j t j j ! ' ! ; i j. ; THE OVER Involvement of the liver, with jaundice, sometimes ascites, was noted in early observations us a sequela of arsenical medicalion. Hutchinson (1687), for example, described liver injury resembling cirrhosis following arsenical treatment of chronic eczema. One of the first records of cirrhosis from the industrial use of arsenic was that of Doric and Ziegler (1930) in wine dressers, j t >' e [. ARSENIC AND ARSINI3 Jl llmugh, us already remarked, us In that of many successive observations on wine dressers in Germany, the ingestion of arsenic-contaminated wine is now believed to play u more important part than the actual esposuio to the arsenical insecticides, Hurren uiul lieiulem (1941) slated that the increase in liver injury among employees In the wino industry since the introduction of arsenic spraying was to be largely attributed lo the citeel of arsenic, and that this injury was degenerative in character, repartible in some eases, but leading finally to cirrhosis. On the basis of the Takala-Ara reaction they found that 70 per cent of the workers examined showed n variable degree of liver injury though only 36 per cent showed a definite cirrhosis. In a fatal caso with ascites u special feature was tlsc presence or discrete parenchymal necrosis with reparative connective tissue formation. They conceded, how ever, that the influence of ingested alcohol could not be entirely excluded. This Reservation applies also to the supplemental toxic action of nicotine, phosphorus and metabolic disturbance in similar observations by German authorities in the early years of this century. DISORDERS OF THE HEART AND CIRCULATION The subjective and clinical evidence for a primary cardiac injury in arsenic workers is not very definite, but the electrocardiograph has revealed abnor malities similar to those observed in animals fed on subtoxic amounts of arsenic (Butzengeiger, 1940 and 1949; HadjolofT, 1940 and 1957). Among 216 wine dressers using arsenical insecticides, Butzengeiger found 55, who showed other symptoms of chronic arsenical poisoning, lo have an abnormal electrocardiogram indicating a toxic myocardial effect. Among these were 36 whose myocardial injury was severe, and some of them were suffering also from peripheral disturbances indicative of endo-angiiiis--gan grene of the extremities, atrophic acrodermatitis and oilier loss severe symptoms of peripheral damage. Butzengeiger described the endo-angiitis as indistinguishable from severe arteriosclerosis or endo-angiitis obliterans. ! THE CARCINOGENIC ACTION OF ARSENIC Examples of cancer of the skin in patients receiving arsenical medication and in arsenic workers having external contact with arsenical compounds have I already been described, and there seems little doubt llut carcinomas of the skin do arise especially on the sites of arsenical keratosis^ The evidence for arsenical cancer of other organs is not so universally accepted, especially will! regard to occupational exposure.. The view formerly held that the high incidence of lung cancer among the miners of Schnccbcrg and Joachimstal were due to arsenic lias been more or less discarded in favour of radioactivity as the carcinogenic agent, partly because of the absence of characteristic arsenical skin changes. Hueper (1942) stated that " the possibility of a causal relation between the inhalation of arsenic dust and the development of pulmonary maliliiv.mcv may be con ceded bat the probability of its relationship is small '*, In a clinical und experimental study by Perry el at. (19-18) among workers t ~J2 TOXICITY OP INDUSTRIAL MliTAl.S ARSQNIC AND AKSINC in n factory manufacturing a solution of sodium arsenate, despite the previous finding by Mill and Patting (1948) in llie same factory that on a statistical Arsine basis there was a greater tendency for arsenic workers to die of cancer than for otiter rtroups" radiographic examination did not reveal any casc-lif Arsine (nrseniuretted hydrogen; hydrogen arsenide; AsII,) is nut an industrial product in the economic sense, but an accidental evolution when* i J bronchogenic carcinoma. More recent investigations by Rollt (1956, 1957) ever nascent hydrogen is liberated in the proximity of trivalcnt arsenic. I ' and Braun (1958) do, however, show a definitely higher incidence among wine ' ! dressers in Germany. Roth found 10 eases of bronchial carcinoma among I 30 workers with arsenical skin lesions, llraun, comparing the incidence of PROPERTIES Wonchjal cancer in those suUeimg from arsenical dermatoses during tlie Arsine is a colourless inflammable gas with a slight garlic-like odour, years I9SI--1957 with that between 1939 and 1952 found a greatly increased incidence in the later year*. Out of Id of an average age of 52 years, all depositing arsenic on exposure to light and moisture (threshold limit value for an 8-hour working day, 0 05 p.p.m.). Concentrations of 3-10 p.p.m. will showing keratosis and some alio melanosis, pre-malignant or malignant skin" produce slight symptoms after several hours' exposure and 16-30 p.p.m. changes, 9 had inoperable bronchial carcinoma. '] are dangerous according to Doig (1958). Tumours of other organs, most frequently in association with arsenical .cancers of live slcin, have also been described, notably by Sommers and OCCURRENCE ! McManus 11953) inIhctr revtcw 'or la cases ofvisceral cancer reported in |i, various countries up to that year. Among these, of . which only 5 were Since arsenic is present as a contaminant of many ores--zinc, lead, copper, Industrial workers, mere were 1 cases of pulmoiury tumour, 3 of the mouth antimony, gold, silver and tin--the formation of arsine occurs most fre r and tongue, 3 of tlie ureter and bladder, 2 of the breast, 2 of die oesophagus, I of the stomach and 1 of die cervix uteri. Only 6 of these had associated cancer of tlie skin. In their own series of 27 cases, of which only 2 were occupational, many had not only multiple skin cancers, but also, among 6 who were subnutted to autopsy, 4 had separate internal cancers of the quently In the metallurgic industry, particularly from the action of acid on . arsenic-bearing metal. It may also occur wlicrc tlie hydrogen ion is formed by hydrolysis, as in the reaction of moisture with calcium arsenide present as an impurity in fcrrosilicon (Hake, 1910); in the process of wetting of | aluminium and phosphate dross (Nau, 1948; Spolyar and Hargcr, 1950); I in lead refining (Wills, 1948; Banik, 1956); and in the purification of tin bladder, prbstate, oesophagus, colon, kidney and chest wall; in 3 cases the - (Macaulay and Stanley, 1956). In this last process reports from those of growths were multiple. Rodi 119561 also noted 5 cases of malignant liver tumour and one of oesophageal cancer associated with liver cirrhosis, and in Braun's series Lcggc (1924) onwards had previously recorded 30 cases of arsine poisoning with 12 deaths. Its occurrence has also been described during cyanide there was l case of carcinoma of the bile ducts also associated with cirrhosis extraction of gold (Uulmer et ol, 1940); in the process of leaching of zinc of the liver, and 1 of a suspected sarcoma of tlie cervical lymph glands. (McKinstry and Hickcs, 1957); very frequently in the cleaning out of Hosset (19511) has recorded a case of multiple internal carcinomas in a man furnaces and tanks (Wills, 1948; Hamilton and Hardy, 1949; Troisi, who more than 20 years previously had used lead arsenate to spray potatoes, and bad at that lime developed kcratotic lesions on the palms of his hands. 1950); and even from mishandling of arsenical insecticides (Mohacck and Stajduhar, 1951). The latent period of development of malignant tumours of possible arsenical origin is long--13-50 years according to Sommers andI McManus (1953), i TOXICOLOGY 13-22 years in the experience of Roth (1956) and llraun ^1958). i The fatal effects of arsine were first reported in 1815, when Gchlcn, a chemist, The most disputed point in tlie problem of the potential carcinogenicity died from inhaling it in his laboratory. It is a powerful haemolytic poison of arsenic appears to bo whether it is a direct agent, or wliellicr it is dependent with both acute and also chronic exposure. In the acme form the nun i.ility on other factors such as tissue susceptibility, skin sensitivity, photosensitivity, rale is high. Muehlbcrger el al. (1928) slated that 20 percent of215 cases of or other external or internal metabolic effects. On this point it docs not poisoning occurring sinco 1815 had been fatal; Spolyar and Hargcr (1950) seem possible at present to arrive at a direct conclusion. Even GoldWatt estimated a mortality of 12 among 30 cases recorded between 1923 and 1941, and Goldblail (1956) in their admirable review or industrial carcinogenesis, while during the years 1945-1946, 13 cases, 4 of them fatal--a mortality and with their extremely wide experience of the subject, can only say that of 31 per cent--were recorded in the Annual Reports of the Chief Inspector " the arsenical compound which produces no tumour in a workman is not of Factories. , ; a carcinogen for him until he, in a given tissue, brings about n meeting t between a cell in the appropriate state and the compound in a sufficient ACUTE YOISONING concentration,.. and... from the very Tew cases of occupational arsenical Tlie outstanding initial features of acute arsine poisoning arc malaise, cancer hitherto reported it may be considered tluit a combination of appro* abdominal cramps, nausea and vomiting, and a red staining of the conjunc- priate stitle and sufficient concentration is rare ", . tiva ; this pigmentation, according to Macaulay and Stanley (1956), is not ucc 002720 t f Industrial Hygiene Dioast March 1971 trifluoride (CIF3), and bromine pentafluoride (BrFg). The data do not suggest the existence of any fluoride-bearing degradation products which behave differently from fluoride ion. NF^ and NjF^ intoxi cation resulted in persistently high concentrations of fluoride in erythrocytes. --Authors' abst. 280 REPEATED AND CONTINUOUS EXPOSURE OF LABROATORY ANIMALS TO ACROLEIN. . J. P. Lyon, et al. Toxicol. Appl. Pncrracol. lfT 726-/ii^ Nov. 1970 ~~~ Experimental animals were repeatedly exposed to acrolein vapors 8 hr/day, 5 days/wk for 6 consecutive weeks in 2 studies at concentrations of 0.7 and 3.7 ppm. Four continuous exposures to acrolein were con ducted 24 hr/day for 90 days at concentrations of 0.21, 0.23, 1.0, and 1.8 ppm. Each experimental group of animals contained rats, guinea pigs, monkeys, and dogs. The animals were observed for toxic signs, mortality, and weight changes, and hematologic, biochemical, pathologic, end histopathologic examinations were made on the surviving animals. In both of the lower-level continuous exposures and in the 0.7 ppm repeated exposure, the animals appeared normal throughout the studies and gained weight. In the higher-level continuous exposures and the 3.7 ppm repeated study, the dogs and monkeys were visibly | affected, and abnormal weight patterns were observed in some animals. The data from repeated studies support the current Threshold Limit Value (TLV) of 0.1 ppm. A tentative 90-day Confined Space Guideline (CSG) of 0.02 ppm is suggested based on data obtained from these studies. --Authors' abst. -.281 ARSENIC AND WATER POLLUTION HAZARD. E. S. Pattlson. Science 170: 870, Nov. 20, 1970 : Undue speculation in the press, scare headlines, and the drawing of widesweeping conclusions about alleged hazards to consumers have resulted from the report by Angino et al. (Science 168: 389 (1970). Under no | circumstances (whether examining raw and treated sewage, raw and treated drinking water, and river water) j were Angino et al. able to present data that indicated that arsenic concentrations remotely approached < those that would disqualify these waters as water supplies. Moreover, finding traces of arsenic in wash water (which is certainly not recommended for drinking, in any case) likewise does not constitute a threat. Angino et al. made no apparent effort to evaluate the impact of the use of farm Insecticides (arsenicals) or industrial and municipal discharges on the one river they studied (the Kansas River). In fact, all they demonstrated was that arsenic, in trace quantities, is a ubiquitous material found widely in nature and that It does not constitute a hazard to water quality at the concentrations they reported. i --Cond. from text ,282 THE ARSINE HAZARD. Anon. Laneet 1: 71-72, Jan. 9, 1971 r Arsine poisoning, within or without Industry, Is rare, which Is fortunate since arsine (arseniuretted ! hydrogen) is one of the most poisonous of industrial fumes. Until lately, the prognosis of severe j poisoning was grave. It Is not produced intentionally in industry, for It has no contnercial use; so I . poisoning results from the chance contact of nascent hydrogen and arsenic, or the watering of an arsenide, i Greater awareness by the Industries concerned of the dangers of chance arsine evolution has undoubtedly prevented accidents. Improvements in exclusion of arsenic as an unwanted contaminant in industrial processes have worked to the same end: for example, modem production methods produce an arsenic-free sulphuric acid. The possibility has been raised of the missed mild case of arsine poisoning. Mild poisoning unaccompanied by oliguria may remain unrecognized and should be considered in the diagnosis of hematuria or jaundice in a patient whose occupation brings him into contact with acids and metal. --Cond. from text 19. ucc 002721 <<*! nvciene Digest January, 1964 47 Distribution of Se-75 ih Serum Proteins of Chicks and Influence of Selenium oo Albumin Recovery. E. D. Walter, L. $. Jensen and J, S. Dunlap. 1 Froc. Soc. Exptl. Biol. Med. 114, 527-530 (Nov. 1963). Se-75 wii orally administered to 3-week-old chicks fed either selenium deficient or supplemented diets. Distribution of Se-75 in serum proteins with time and its effect on serum protein pattern were determined electrophoretically. Selcnium in the diet had no effect on the distribution of Se-75 in the protein fraction, but markedly decreased its retention. After 2 hours the major portion of the dose was found in the beta and gamma fraction and the activity in this fraction increased with time. Marked increases in A/G ratios in depleted chicks were observed within 96 hours after administration'of Se-75. Albumin was increased and globulin fractions were decreased. Increases io A/G ratios, somewhat smaller in magnitude, were also noted in chicks receiving a diet supplemented with selenium. ' -- Authors' summary 48 Effect of Arsenic Trioxide Exposure on Mortality. S, S. Pinto and B. M. Bennett. Arch. Envi'^onmenEaf rUalth 7, 583-591 (Nov. 1963). A study has been made in a copper'smelter of the causes of death among present and pensioned employees dying in the period 1946-1960. The influence of arsenic trioxide exposure was specifically reviewed. Previous work had shown men in this plant not exposed to a.rsenic excreted an average of 0. 13 mg. arscnic/liter urine; those exposed excreted an average of 0.82 mg. arsenic/liter urine. There was no evidence that chronic arsenic trioxide exposure of the . amount described in this* study is a cause of systemic cancer in bumans. Industrial arsenic tri oxide exposure of the aniount described in this study bad no measurable effect on fatal cardio vascular disease. Thirty-six references are given. - - Authors' summary 49 Some Problems in the Large Scale Handling of Beryllium. F. B. Crossley. Ann. Occ. Hyg. (London) b, 89-103 (April-June 1963). A highly technical description is given of the beryllium pilot plant at 1C1 Metals Division at Birmingham. The maximum permissible concentrations are: (a) in the process area, (1) over any 8-hour'period, 2 micrograms/cu.m. in the breathing gone, (2) the daily average must be within this limit but for any 30 minutes must not exceed 25 micrograma/cu.m.; (b) outside the process area concentrations must not exceed 0.01 microgram/cu.m, averaged over a month, calculated with reference to the breathing sonc, This is observed by stack monitoring. Before the plant started working, measurements of beryllium air levels made in the Birmingham area were well above the tolerance level. Control of the beryllium dust content of the air in the plant is achieved by ventilation techniques which are described in detail. The control of the personnel in the areas where beryllium is worked is obtained by pre-employment examination with x-ray examination, and subsequently at intervals of 6 months. The provision of special clothing and of cleaning facilities and the use of masks and air-fed pressure suits arc described in detail. -- Bull. Hyg, 50 Delayed Carcinoma from Beryllium Aerosol in Man. H. K. Niemoller, Intern. Arch. Gewerbepathol. Gewerbehyg. 20, 180-186 (1963). German. Various authors have reported the production of malignant tumors in animals after exposure to beryllium salts. The present paper presents 3 cases which confirm for man the results obtained by Schepers in animals. The first patient had come into contact with beryllium compounds in the form of dust, fumes, or gas at work for a period of 3 years. From 1943, he bad no further exposure. In 1946, his chest x-ray showed an appearance interpreted as due to beryllium; he was given a pension. In 1959, he developed a cancer of the lung and died of.intracranial pressure due to cerebral metaxtases in I960. The lungs did not show the typical beryl lium granulomata but there was a diffuse fibrosis. The lung tissue on spectrum analysis gave a positive finding for beryllium. This may be the first case in world literature described as a late beryllium carcinoma. The second patient was employed for 15 years in .a beryllium factory.and at the end of that time in 1945 was found to have typical signs. In 1961, an increased shadow on* the right side of the mediastinum was investigated. Cells of a squamous celled carcinoma were ^'T .LUIJfPW. 13. M. ucc 002722 --- ^ ifir -a it'Vnit.'b ,- it;,.,...> - r.L.--....... ................. .. - -- - industrial Hygiene Digest February. 1964 142 Physical and Psychologic Factors in Clue Sniffing. O. N. Massengale, et al. New Engl. J. Med. 269, 1340-1344 (Dec. 19, 1963). Twenty-seven children who were chronically habituated to inhalation of cement vapors were seen in the Adolescent Clinic. No physical or laboratory abnormalities directly attribut able to contact with glue were detected. Personality patterns in this group of children were re markably similar. Toluene was found to be the major volatile component of commonly used ce ments subjected to gas chromatographic analysis. Available information regarding the toxicity of this compound when inhaled is conflicting. Although glue sniffing appears to be physically harmless to most children, it is an increasingly prominent stimulus to delinquency. The authors list 26 references. -- Authors' summary 143 Evaluation of Fluctuating Carbon Monoxide Exposures. J. R. Goldsmith, J. Teraaghi and J. D. Hackney. Arch. Environmental Health 7, 647-663 (Dec. 1963), The agent, carbon monoxide, was shown to fluctuate over time and place. This is a major factor in effects of exposures of human populations. The patterns of population exposure must include the exposure of cigarette smokers, of those subjected to community air pollution, those with exposures to motor vehicle exhaust during commuting, and those with occupational exposure to carbon monoxide. A reasonable division of the population in a community was shown to consist of 6 different categories. Another important population variable consists of those unusually sensitive to impaired oxygen transport because of age or medical status. The mech anism of action is predominantly the impairment of the oxygen transport function of the blood. Other possible mechanisms were discussed. A mathematical approach for predicting the time course of carboxyhemoglobin, given the temporal fluctuation of carbon monoxide was derived. These mathematical expressions required some simplifying assumptions. The expressions were used to develop a computer program, and, with a simulated set of sinusoidal exposure data, the expected carboxyhemoglobin was calculated by using a method of interative integration. Several sets of experimental data were approximated by both analog and digital computer techniques. The possible synergistic effect of other pollutants was reviewed. -- Authors' summary 144 Carcinogenesis Tests of Two Inorganic Arsenicals. C. Baroni, G. J. van Esch and U. Saffiotti. Arch. Environmental Health 7, 668-674 (Dec. 1963). Arsenic trioxide was tested by oral administration and sodium arsenate by skin application on Swiss mice. Each compound was tested in 3 ways: (1) alone (carcinogenesis test); (2) in combination with skin applications of the promoting agent croton oil (test for initiating action); and (3) after initiation with a single skin application of 7,12-dimethylbenz(a)anthracene or with administration of urethan by stomach tube (test for promoting action). Control groups were studied concurrently. All tests failed to show any carcinogenic, initiating, or promoting activity of the 2 arsenicals under the experimental conditions used. In view of available evi dence indicating that certain exposures to arsenic represent a human cancer hazard, further studies on the role of arsenic in carcinogenesis are considered necessary. There are 25 references. -- Authors' summary 145 The Fate of Cd- 109 in the Mouse. An Autoradiographic Study After a Single Intravenous Injection of Cd-109 Cl?. M. Berlin and S. Ullberg. Arch. Environmental Health ^7. 686-693 (Dec. 1963). The body distribution of cadmium in mice killed at various' times, from 5 minutes to 16 days, after a single intravenous dose of 8 microcuries Cd-109Cl2> carrier free, was studied by autoradiography of sagittal whole-body sections. The relative order of concentrations found in the organs of ths body was estimatsd by densitometry. The distribution is described in de tail. The autoradiograms indicated excretion of cadmium by gastric and colonic mucosa and in the bile. Very little elimination of cadmium, however, was found to occur during the 16 days of observation. Cadmium concentration was seen to decrease only in the mucosa of the intestinal tract, where it fell rapidly after 24 hours. Considerable amounts of cadmium were demonstrated for the first time in the interstitial tissue of the testes and in the posterior and anterior lobe of the hypophysis, A distinctive pattern of localization in the renal cortex was also found, indicating selective accumulation in special structures. -- Authors* summary 12. n.j ucc 002723 n*uu>cf ui pyginc mggst. April, 1969 375 Burn Therapy; V. Disaster Management--To Treat or Not to Treat? Who Should Receive Intravenous Fluids? A. W. Phillips. Ann. Surg, 168. 986-996 (Doc., 1968). In a disaster, when there are more burn casualties than can be cared for by the available per sonnel or when medical supplies are limited, a knowledge of the probabilities of survival for patients of varying ages with varying burn extents will aid in achieving the maximum number of survivals. A helpful rule is the Adult Rule of 90, worked out from actual burn statistics. Adults whose age plus burn extent exceeds 90 have less than a 50:50 chance of survival. If everyone cannot be treated, these should be among the first for whom palliative management is considered. If the situation improves this rule can be softened to 100 or, if supplies and personnel are still insufficient, it can be dropped to 70. Conventional treatment should be resumed at the earliest possible opportunity. If this rule had been used on 932 consecutively admitted burned adults at the Massachusetts General Hospital, only 12 who actually survived would have been denied fluids. At the cost of those 12 lives, 1, 000 liters of fluid would have been saved, enough to treat 60 adults or 120 children in whom it might spell the difference between life and death. --J. Am. Med, Assn. References 8. Reviews 376 Intravenous Glucose Tolerance, Insulin, and Free Fatty Acid Levels in Burn Patients. S. P. Allison, P. Hinton, and M. J, Chamberlain. Lancet^, 1113-1116 (Nov, 23, 1968). Intravenous glucose tolerance tests performed during the shock phase of burn injury and repeated one to four weeks later show that in the shock phase there is giucose intolerance, a high level of free fatty acids, and failure of the plasma immunoreactive insulin level to rise in response to intravenous glucose. These changes were related to the severity of the burn; they may be due to the high level of epinephrine secretion found in such patients. In the later phase there were higher than normal blood levels of fasting insulin and of insulin response to glucose, suggesting insulin resistance. Burn patients should be put on a high-carbohydrate regimen in the form of glucose and insulin or of fructose. --J. Am. Med. Assn. References & Reviews 377 Magnesium Deficiency Syndrome in Bums. A. Broughton. I. R. M. Anderson, and C. H. Bowden. Lancet^, 1156-1158 (Nov, 30, 1968). Twenty patients with burns were investigated for the magnesium deficiency syndrome. Eight showed a significant fail of serum magnesium, and five of these had symptoms of magnesium deficiency. Some of the psychiatric symptoms exhibited by many burned patients may be due to or aggravated by magnesium deficiency. --J. Am. Med. Assn. References & Reviews 378 The Effect of Ingested Arsenic on Methylcholanthrene-Induced Skin Tumors in Mice. J. E. Milner. Arch. Environmental Health 18, 7-11 (Jan.. 1969), Three strains of mice (C X C3H, DBA, and Balb/C) were selected on the basis of differing vigor or potentiality for cutaneous tumor development or both. These animals were fed arsenic tri oxide in their drinking water in a concentration of 0. 01%. Cutaneous tumors were initiated by the topical application of methylcholanthrene disks and promoted by transplantation. Although arsenic treatment appeared to increase the number of papillomas, produced in the DBA strain, the effect was not statistically significant. The C X C3H mice, however, displayed an opposite effect, in that arsenic treatment resulted in a decrease in the number of papillomas produced. This effect was statistically significant with a P value <0. 05. There are 20 references. --Author's abst. I CHEMICAL HAZARDS I 379 Teratogenic Effect of Cadmium and Its Inhibition by Zinc. V. H. Farm and S. J. Carpenter. Nature 216, 1123 (Dec. 16, 1967). Pregnant hamsters were injected intravenously on the eighth day of gestation with either 2 mg. /kg of cadmium sulfate, 2 mg, /kg of zinc sulfate, or a mixture of 2 mg. /kg cadmium sufate plus 2 mg. /kg zinc sulfate. Zinc alone provoked a very mild teratogenic response. In identical conditions, cadmium caused a marked embryocidal and teratogenic effect; approximately 66% 17. jj..i 'j,', ,ji jjwii 'H.SJT1VJ, 'IlIJ'U'J.PMI, ucc lyiM* 'CHROMSOtER SCHADlGU*T,Ey ntmCR / TMweLTVERUNREnflOteEx - Lachmt V, - KoUngasse 10, Wien - TEN.MCD.wsa<R. 1972 122/4 (43-49) Substances which may on occupational exposure at (airly high concentrations cause disease or damage health are discussed. Of the many trace elements in inhaled air most are present m such small quantities that damage in health is hardly likely, even in the vicinity of industrial plants etc. Certain metals such as nickel and cadmium ment greater attention in the future, however. Despite their low atmospheric concentration, socalled neighborhood cases have already been reported. Lead is one of the commonest and most severe atmospheric pollutants. Pollution by lead has been largely contributed to by the use of petrol containing lead. Longterm studies show that the maximum allowable concentration of lead may reduce the ' life expectancy of laboratory unimaU. a toxicological effect is also suggested by the reduced activity of ALA dehydratase observed at such lead levels. This may be interpreted as an early sign of the effect of lead on this enzyme, important in synthesis of heme. To prevent further increase of lead levels in the nonoccupationaliy exposed population a rigorous reduction or elimination of the lead content in petrol should be enforced. Some air pollutants have decreased recently in some countries, due to legal action; this has not occurred with asbestos fibers, which art extremely dangerous. The presence of socalled asbestos bodies in the lungs of nonoccupationally exposed people indicates the necessity of further studies, Whether these bodies which give a positive reaction for iron are indeed far the major pan asbestos bodies can only be decided by comparative serial investigations. Poisoning with organic mercury compounds resulting from consumption of mercury polluted fish has occurred not only in Japan (Minimata disease) but also in Scandinavia and Canada. This has led to an investigation of the metabolism of these substances. Organic mercury compounds, especially methyl Hg compounds, have a particular affinity for the central nervous system. Determination of mercury in plasma or urine in cases of poisoning by these compounds yielded quite low Hg levels, though in whole blood or organs the level was much higher. For this reason mass poisonings have frequently been interpreted incorrectly. Prevention must consist of prepurification of waste water of the appropriate industrial plants; 423. Health aspects of nitrates in drinking water - DEVELOPMENT* IN WATER OOAUTY RESEARCH . Gruener N. and Shuval HJ. . axn ardor somdl, 1970 (89-90) The danger of water contamination by nitrate salts is dealt with in this article. Recant developments have created the need to embark on a study to determine if present nitrate concentrations in drinking water are having any detrimental effects on the population exposed. In addition, the authors felt that a basic reevaluation of the nitrate standard in drinking water was called for, since this standard was originally based on very limited toxicological end epidemiological information and has been subject to criticism for some years. Ot particular concern has been the suspicion that a form of subclimcat chronic methemoglobinemia might exist in infants in those areas with moderately high nitrate concentrations in drinking water. Consequently, the present state of knowledge concerning nitrate methemoglobinemia is also reviewed. 424. Health aspects of arsenical in the environment - Liselia F.S, Long KJL and Scott H.G. - Dept. Prev. Med. Environm. Hlth, ColL Med- Utuv. lows, Iowa City, la. 52240 - LEXViROKMJaTH 1972 34/5 (511-518) In a literature review on arsenical compounds, this paper points out the possible hazards to human health and the environment resulting from their use. The major headings of this review include: the contemporary uses of arsenicals, illness and death associated with arsenic, arsenicals in the environment, and analytical procedures for the detection of arsenic. 425. Role of cadmium in human and experimental hypertension - Thind G.S. - Dept Med. Sch. Med. Univ. Pennsylvania. Philadelphia, Pa. 19148 - JAM rouxontrol ass. 1972 22/4 (287-270) Acute and chronic studies performed in the authors' laboratory in normal rabbits, dogs, human control subjects, and patients with hypertension are reviewed. Cadmium, a common contaminant of air, water, and food, produces persistent hypertension in the rabbit and dog. The pervasive metal Is predominantly deposited in the kidney and liver, and to a lesser extent in the blood vessels of the cadmium hypertensive rabbits. Vascular responsiveness to angiotensin in the cadmium hypertensive aortic strips was significantly lower than that of the ships obtained from control nonnotensive rabbits. Cadmium hypertensive aortic strips also developed significantly lower passive tension On step wise increase in the original length of the strips (strain). Administration of cadmium acetate directly into the renal artery, preceding the injection of the vasopressor (angiotensin, epinephrine or norepinephrine), resulted in a dose related reversible inhibition of the vasopressor induced renal vasoconstriction. It is probable that significant pathophysiological changes In experimental cadmium hypertension would occur in the vascular system and the kidney, where . cadmium deposition was the greatest Main plasms i.,ti levels ware significantly higher in patients with hypertension. Plasma zinc levels, however, were significantly lower only in hypertensive patients with renovascular and renal parenchymal disease but not in essential hypertension patients. A program of detailed epidemiological studies and public health measures is needed for further definition of the role of cadmium in idiopathic human hypertension. 428. Alkyl mercury poisoning in humans. Report of an outbreak - Flares P, Thompson JF. Likosky WJL ct iL - 845 Central Ava, Albany, N.Y. 12208 - JAMOUtEDASa 1972 220/11 (1439-1442) Three members of family of nine that ingested mercury contaminated pork became ill 73 . ^.m.. n i mu--wrewew" -tMAww?CP| wreion ' ; . Ucc 002725  ------ . oU-rrVii. L "-JW-'T* -*~~*rT*,L' la u i:__ j so they have vaccinated council stall against 2/7666 (253) influenza in the autumn. It has not been possible Editorial. Brief review of recent literature on .4 accurately to assess the value ot the procedure, this problem. but last winter's figures are of some interest though the number are smalL Difficulties arose in 923. Carcinoma of pancreas due to effect of obtaining vaccine against the Hong Kong strain arsenic in a seiremployed iarmer and' vineyard in the autumn of 1968, and a monovalent vaccine tender - aukkeas c* ditch AXStvei.veutKLCvC att did not arrive until January 1969. As the EDItat SdSSTANDIGEN LAUDWTXT UNO WTlNCAimtH . expected epidemic had not yet materialized it FinzeJ L. - Dicnitst, Staatl. Gcwerbearxtes was decided to vaccinate those who were willing. Gewcrbcaufsichtsamt Heilbronn - In the autumn of 1969 vaccination again was MtBEItSMEDSOZULMEDJUtBCrriHYO. 1970 3/9 (231-232) offered with a bivalent vaccine. In the first 23 During the years 1937 to 1939 a farmer had vaccinated persons there was an unduly high used (6 times per year) an arsenical insecticide. proportion complaining of minor side effects, and He developed warn, and in 1931 a skin the dose for the remaining 87 was reduced from carcinoma had to be excised. Lymph node' 1 mL to 0.5-0.7S ml, and no further trouble was metastases developed. Ke was under continuous experienced. During the period 16 December 1969 treatment for cancer of the right side of the head .to 27 Jsnuary 1960 an outbreak of influenza and neck up to 1962. la 1966 jaundice developed, occurred as part of tha national epidemic with a and he died in 1967. At autopsy a carcinoma of peak locally in early January, when claims for the pancreas was found. A relation Between his sick benefit reached a weekly figure ot disease!*) and his former occupational activities approximately 6302 above the seasonei average. was accepted by the insurance company- Strains of tha Hong Kong variant Of influenza virus A2 were isolated In the area. Returns from 924. The future and lung cancer * Haddow AJ. - councils of absence owing to illness, believed to HEALTH (Lends 1970 7/2 (23-23) be influenza, during December and January were The impact of lung cancer on the population as follows: Unvaecinsted 164. off sick 41; has changed enormously during this century and. vaccinated once only 27. off sick 7; vaccinated to appraise what the future may bring, it is twice 33, off sick niL From this it will be seen necessary to outline the events ot the last few that there is no difference in the absentee rate decades and the present position. Death rate of those who were unvaccinated from those who from lung cancer is increasing. There is reason received one dose only in November 1969. In the to anticipate that the rate in males will continue case of those who received two doses there were to increase for a number of years, and that no absences, anil this is statistically significant. mortality in v/oman wiU scon begin to increase Although one cannot draw any Arm conclusion much more rapidly. In other words, it is believed because of the small number who received one that in the near future we shall face a much dose only, and in 23 a reduced dose, the authors worse situation than at present. The age factor, think it seems prudent to advise an initial course and the role played by cigarette smoking are ot two doses in the previously unvaccinated and mentioned- The smoking habits and lung cancer where there has been e significant change in the mortality of women are 20 yr in arrears of the strain of the A2 virus. men and, if the present trend continues, they could, in the next 20 yr, reach the male mortality level Smoking in men is still increasing, but not as rapidly as formerly; in. women it is increasing u. carcinogenesis very rapidly. Air pollution is not a major factor. Unless tobacco consumption can be checked, little 921. World maps ol cancer mortality rates and can be done, Tha situation will almost certainly frequency ratio*. Paris lit and IV (conclusion) deteriorate further as smoking during school days Dunham- LJ. and Bailar IQ J.C. - Nat Cancer is looked on more leniently today, with the result Inst, Betbesda. Md. iNotantiuDSuao. 1970 39/3 that more children leave school already confirmed (37-33) and often heavy smoker*. As the latent period This is a continuation of a series which seems to be between 13 and 20 yr. it may be includes 14 maps of cancer mortality ratios and expected that lung cancer cases among people in frequency rates, based on a review of cancer data their thirties will be seen. . by geographic areas. Mora than 100 such areas are included. The data an recorded oo maps tor the following cancers in males: oral cavity and pharynx, esophagus, stomach, intestines aid IS LABOR AND MORBIDITY : t rectum, liver, larynx, lung; and bronchus, prostata, . urinary bladder, and leukemia. Data tor females i 18X Circulatory system - are given tor the following sites of cancan oral cavity and pharynx, esophagus, Intestines and 923. Exercise and hypootherapy in the . rectum, breast and uterine cervix. The data,are rehabilitation of tho coronary patient - Kavanagh arranged in sequence by International List T. Shephard RJ, Pandit V. and Done/ H. - - . numbers, with male* placed before females where Rehab. Cant. Toronto - AJiQUHYSJrtO. 1970 31/10 both sexes era included. The present publication . is adapted from a longer article published in the . Journal of tha National Cancer Institute, VoL 41. (378-367) A comparison was made of 2 rehabilitation programs for patients after coronary occlusion. The first consisted of progressive physcial 922. Nasal cancer la woodworkers - uwsr 1970 exercise under the supervision of a physician and / 178 ''nJ^istrial Hygiene Digest 'ill- 1 kiuiliU, ________November, 1964 j 1093 Methemoglobinemia Caused by Spinach Containing Nitrites': Preliminary Report. A. Siniot, Munch.med. Wochschr. 106, 1180 (June Z&7 1964). A gray, livid color was observed in three infants, 3 and 4 months of age, from one to two hours after they had been fed spinach. Until then the infants had been well. The livid coloration was accompanied by tachycardia. The blood was chocolate brown, and a spectroscopic examination revealed methemoglobin. Large amounts of nitrite were detected in left-overs of the spinach fed to two of the infants, and the spinach found in gastric washings of the third in. fant contained some nitrite. Feedings with the same spinach puree had caused no symptoms on the day before. The spinach had been stored at room temperature. The author reasons that the nitrite must have derived from the multiplication of nitrite-forming bacteria in a spinach puree which contained nitrates, so that the nitrate was converted into nitrite. Studies have been started which suggest that this explanation Is correct. The great sensitivity of young infants to toxins forming methemoglobin has been proved earlier by methemoglobinemia developing in infants whose formulas had been prepared with well waters containing nitrates. -- J. Am. Med. Assn. References & Reveiws 1094 Investigation of SOz Effects on Rubber Trees as a Means of Forestalling Injury to Malayan Plantations from Refinery Emissions. Eileen Brennan, Ida A. Leone, and R.H, Daines. J. Air Poll. Control Assn. 14, 229-233 (June, 1964). Four-hour fumigations of dry rubber trees under conditions simulating the climate of Malaya did not produce injury until the concentration of 0-7S SO* ppm was reached. Fifteen- minute exposures of the trees failed to cause injury until the concentration of 75 to 100 ppm SOj was reached. When rubber plants having wet leaves were fumigated for a 4-hour period, slight injury was produced at 0.40 ppm SOz. Total sulfur determinations of composite dry leaves showed no significant increase over than in untreated checks until the concentration of 0.70 ppm SOz wa* reached. Trees which were fumigated wet showed a significant increase in total sulfur content over dry check trees even at the lowest SOj concentration of 0.13 ppm. Old leaves consistently had a higher total sulfur content than did younger leaves. In young leaves a con. siderable part of the absorbed sulfur (up to 30%) could be washed off the surface, whereas old leaves or composite samples failed to show any decrease in sulfur content on washing. This might be used as a criterion for exposure of foilage to atmospheric SO*. A 3 week fumigation at 0.30 ppm SO*. the maximum concentration predicted by Esso engineers in the Port Dickson area, failed to produce any injury symptoms. A total sulfur content of the foliage sufficient to cause injury when accumulated at a rapid rate failed to injure when accumulated over a 3 week period. Respiration studies failed to indicate the possibility of hidden injury occurring during this prolonged fumigation. Rubber trees respond similarly to other woody species to the presence of SOz, being injured at much higher concentrations than were most of the herbaceous species tested. -- Authors' summary 1095 Arsenic Induced Carcinoma of the Skin and Lung. C.C. Hill. Penna. Med. J. 67, 35-38 (Sept. 1944). It has been known for more than 75 years that inorganic arsenic in its trlvalent form is a potent carcinogenic agent. Since Hutchinson (Brit.Med. 3.2, 1280 (1887)) reported the association of arsenical keratoses with carcinoma of the skin, there have been many cases re ported of arsenical keratoses. Subsequently, relationship to multiple cancers of the skin was more significant and keratoses became important as evidences ofearly malignancies. Exposure to arsenic is not only associated with an increased incidence of multiple cutancoue carcinomas, but with increased frequency of carcinomas of internal organs as well. Ihe present case of a 47-year-old male is presented as an example of a patient in whom dermatitis herpetiformis was treated with oral Fowler's solution and in whom subsequently developed the typical arsenical dermatoses, Bowen's disease of the skin, cutaneout squamous cell carcinoma, and carcinoma of the lung. The long-latent interval of carcinogenic action of arsenicals was manifested in this <la$e by appearance of cutaneous carcinoma approximately Z0 years after known ingestion of arsenic In the form of Fowler's solution. A long-latent period, however, is not necessary for all patients, as according to Rosset, many patients with psoriasis have been taking Fowler's solution for over 30 years, while some cases have demonstrated malignancy after a short period ` i ; ! j i ! * j i [ ! ' *. ' j j , * j i { ; j j j j j j [ j ; i J5. ucc 002727 Industrial Hygiene Digest November, 1964 of therapy and after ingesting varying amounts of the drug. Arsenic induced carcinoma of the skin and internal organs continues to occur despite almost a centrury.old knowledge of the neoplastic inducing properties of arsenic. This is probably one of the few malignancies which can be almost completely prevented, yet, exposure in the form of medically prescribed drugs, multiple occupational uses, and the eVer increasing content of arsenic in American cigarettes continues. 1096 Serum Aspartate and Alanine Transaminase Levels in Workers Exposed to Lead. H.A. Waldron. J. Clin"Pathol. 17, 149 (March, 1964). Serum aspartate and alanine transaminase levels were studied in a group of 46 workers exposed to lead. In none of them did the level of either enzyme vary from the values found in a group of 50 healthy persons with no industrial exposure to lead. No correlation was found between levels as aspartate transaminase or alanine transaminase and blood lead concentrations. -- Public Health Eng. Abets. 1097' Exposure to Aromatic Hydrocarbons in a Coke Oven By-Product Plant. E.B. Hay.IH. Am. Ind. Hyg. Assn. J. 25, 386-391 (July-August, 1964). _ This paper presents a study of aromatic hydrocarbon (benzene, toluene, and xylene) exposure in a coke oven by-product plant of an integrated steel mill. Three commercial aromatic hydrocarbon detector kits were used concurrently and evaluated for field use. The accuracy of each detector was determined by a comparison with results obtained by collecting the air-borne aromatic hydrocarbons in a silica gel absorption apparatus and subsequent laboratory analysis. The ratio of inorganic to total sulfate in the urine was utilized as a bio logical index of exposure, and the results were compared with time weighted average con centrations to which the individuals were exposed. The study showed no excessive aromatic hydrocarbon exposure to employees in this plant. -- Author's abst. 1098 Methane Diisocyanate: A Respiratory Hazard? E.O. Longley. Arch. Environmental Health 8, 898 (June, 1964). As the search of the literature disclosed no references to the development of respiratory symptoms following exposure to methane diisocyanate (MD1), the author reports an incident which may indicate the need for caution when using this material. MD1 was applied as a rigid foam insulation to the inside of a railway carriage standing inside the main doors of a carriage work shop. The team applying the MD1 wore full protective clothing and air supply respirators. A gentle breeze carried mist from the over spray into the interior of-the workshop. Despite the fact that 12 employees working in the workshop moved to points 60-120 feet from the spraying area, all of these employees developed symptoms, the onset of which varied from an hour to several hour* after exposure. Of the 12 men, 7 developed asthmatic breathing, 11 experienced retrosternal soreness, 12 noticed a constriction of the chest, 10 had a cough which in most cases was paroxysmal and in a few cases, persisted for 7-10 days. Two men noticed a pain behind the eyes, one was "depressed" for 24 hours, 2 suffered headache, 2 had nasal discharge, and one had insomnia on the evening of exposure. The men wearing respirators while spraying were unaffected. The occurrence of symptoms in the 12 men, following immediately upon ex posure to the mist from MD1 would suggest that toxic levels of MD1 can be expected when a spraying technique is employed. 1099 Respiratory Exposure of Volunteers to Parathion. W.V. Hartwell, et al. Arch. Environmental Health 8, 820-825 (June, 1964). Although toxicants generally are believed to be more dangerous when ingested or in haled, most reports assessing the hazards from occupational exposure to parathion suggest that the majority of occupational accidents are due principally to dermal exposure. Previous observations of the authors indicated that some individuals could sustain massive discrete dermal exposure to parathion without clinical evidence of poisoning or significant depression of 16. UCC 002728 Industrial Hygiene Digest October, 1964 990 Multiple Carcinomata Following Ingestion of Medicinal Arsenic. S. Minkowitz. Ann. Internal Med. 61, 296.299 (Aug. 1964). A 21.year-old white male was admitted to the Kings County Hospital Center in 1947, because of a painless ulcer of his tongue that had first been noticed 6 weeks earlier. Past history revealed that he had had Sydenham's chorea between the ages of 7 and 16 and that he had taken 10 minims of undiluted Fowler's solution 11%, calculated as AS^O^) daily be tween the ages of 7 and 10 on the advice of his family physician; a total dose of 7.8 g, of ASjbj as Fowler's solution over a 3.year period during his childhood. He finally bore about 3 dozen warty lesions scattered over the entire body. Many were present on the palms, soles, and trunk. Nine of his lesions were found to be individual primary epidermoid carcinomata. Two of these arose on mucosal surfaces. Seven of the biopsied lesions contained foci of Bowen's disease and one had the histologic characteristics of a keratoacanthoma. Fowler's solution, extensively used for innumerable disorders in the past, has been the medicinal form of arsenic most frequently incriminated in carcinogenesis in the literature. Even relatively minute doses of arsenicals have occasionally been reported to be followed by typical tumor formation. Widely ranging tissue levels of this element in similar lesions from different patients, and a considerable variation among different specimens taken from the same patient, have been found. The quantity of arsenic present in the tissues appears to bear no precise relationship to the dose and duration of the arsenical exposure and to the lapse of time after the exposure. It has been suggested that the presence of this element in a given specimen cannot be regarded as proof of its having an etiological relationship to the lesion at hand, just as its absence cannot justify its being excluded as a causative factor. A brief review of the pertinent literature is presented. 991 ' Carcinogenic Risk of Iron.Dextran. Editorial. Brit. Med. J. 1, 1583 (1964). In 1960 Imferon, a complex of colloidal ferric hydroxide and low molecular weight dextran, was removed from the market following the demonstration of its carcinogenicity in rats,mice and hamsters. Because the experimental doses were large,it was felt that the risk of therapeutic doses was small and the drug was reintroduced. At that time Haddow felt that carcinogenicity could not be excluded until treated patients were followed up for 15 to 20 years. Haddow's recent demonstration of carcinogenicity in rabbits, followed for 4 years, emphasizes again that iron-induced tumors may not appear in man for another decade. Suggestive evidence that iron may be carcinogenic for man is found is the cause of hemochromatosis, in which there is a higher incidence of carcinoma of the liver than with other types of cirrhosis. Iron is readily removed from the injection site in the presence of anemia, and it is possible that this factor, coupled with the use of doses in the therapeutic range, and changing sites of in oculation, will prevent tumor development in man. Hemosiderosis of the liver with anemia is not accompanied by carcinoma. Whether Imferon can induce tumors in anemic animals re mains to be determined. With our present state of knowledge Imferon, administered intra muscularly, should be given only for the treatment of resistant anemias when the immediate benefit outweighs possible future carcinogenicity, and for elderly patients when insufficient time would be likely to elapse for development of tumors even if the risks exist. -- Can. Med. Assn. J. Absts. 992 Toxicological and Biochemical Studies on Some Trialkylgermanlum Compounds. Jill E. Cremer and W.N. Aldridge. Brit, j" Ind. Med.2r7"2'l4.217 (July7 l964). The toxicity of triethyl-and tri-n-butyl-germanium acetates has been studied after their administration to rats. Both compounds had a low toxicity. Triethylgermanium had less than one-tenth of the toxicity of triethyltin or triethyl-lead and, unlike them, it did not appear to have a predominant action on the central nervous system. In biochemical studies in vitro, tri-n-butylgermanium was found to be more active than trimethyl-, triethyl-or tri- n-propyl.germanium in inhibiting both glucose oxidation by slices of rat brain cortex and processes involved in oxidative phosphorylation by rat liver mitochondria. All the german ium compounds tested had less than one-hundredth the activity of the corresponding tri- , alkytin and trialkyl-lead compounds. - - Authors* abst. i ii ! i t I ! I I i 17. 002729 Industrial Hygiene Digest October, 1964 cancer in Connecticut is a significant problem. During the 17 year period of 1935 to 1951 in Connecticut an average of 143 persons died each year from cancer which originated in the mouth. Since that period of time, Connecticut has had its share in population growth and it is fair to assume the current number of deaths caused each year from mouth cancer is now substantially higher. Early detection and early treatment of mouth cancer increases the cure.rates of mouth cancer patients. Since a large percentage of the general population does seek periodic dental care, it is the dentists who are in a particularly advantageous posi tion to play a leading role in early detection of mouth cancer. The new program will be focused on dentists in private practice in Connecticut. Approximately 1,800 in number, this groupmore than any other -- each year has the best opportunity for providing the largest number of comprehensive mouth examinations in the state. However, the program will definitely not be limited to just dentists in private practice. Also to be invited to participate will be all phy sicians in the state, including local directors of health, as well as staff members of all hos pitals and institution*-rfspecially those caring for the chronically.ill and aged population. 969 Medicinal Arsenic Raisoning and Lung Cancer, A. O. Robson and A.M. Jelliffe. Brit. Med. J. 2, 207-210 (July 27, 1963). Six cases of bronchogenic carcinoma are reported in patients who had previously developed arsenical shin changes following the therapeutic administration of arsenic. The average interval between the administration of arsenic and the development of cancer was 32 years. All the tumors were anaplastic in type. Although the relationship between the therapeutic administration of arsenic and the later development of lung cancer is unproved, these cases suggest that such a relationship exists. -- Am. Rev. Reap. Dis, Absts. 970 An Index of the Fate at Circulating Cancer Cells. W.I. B. Onuigbo. Lancet 2, 828-831 (Get. 19. 1963)! Carcinoma of the lung was selected for study because it commonly infiltrates small branches of the pulmeaary vein. Metastatic involvement of the renal glomeruli is relatively infrequent, and special attention was focused on this site. One hundred cases of carcinoma of the lung were investigated: a detailed examination of all organs was carried out with a 2- to 3-cm. block from the kidney, which included the capsule, cortex and medulla, and a part of any metastatic lesim present. Of the 100 cases, there was discrete involvement of one or more glomeruli in 10, but there was little difference in the distribution of metastatic le sions in the liver, tdmul, bone, brain, opposite lung, kidney, pancreas, thyroid, spleen, and extra-tboraeie made, whether or not the renal glomeruli were involved. Because the kidney receives about25% of the resting cardiac output, many cancer cells must pass through the glomerular capillaries, hence justifying the term "circulating cancer cells. " Further investigation of carchoma metastasis is necessary, and the writer suggests that the blood stream itself should ha examined for factors which may determine the fate of the "circulating cancer cells." --Am. Rev. Resp. Dis. Absts. 971 Bronchogenic Carcin^aa in Women. R. Buchbergcr and R.H. Jenny. Wien. Klin. WochschC. 75, 718-72^ (Oct. 18, 1963). German. In the last foe years the frequency of bronchogenic carcinoma has increased in women as well as in men. Babween 1948 and 1960, 120 women were seen with histologically proved bronchogenic carcinema. Forty-four women underwent resection (20, lobectomies: 24, pneu monectomies), 33 wee*found inoperable at thbractomy, and 43 were considered inoperable. In the same period of time 974 resections and 445 thoractomies were done in men with histologically proved bronchogenic <mrcinoma, and 508 men were considered inoperable. In the 1,927 men there wen 442 (23%)peripheral tumors; in the 120 women there were 42 (35%) peripheral tumors. Adenocarcinomas wes* found considerably more frequently in women than in men. The life expectancy of the operated women is slightly better than that of the operated men; the difference is statistically only subtly significant. -- Am. Rev. Resp. Dis. Absts. 11. UCC 002730 \ ,1 I ? y X Industrial Hygiene Digest , 4**>*hei September, 1964 of oral cancer detection programs which should include ; (1) Education sessions for instructing the dentist as to what constitutes a complete oral examination, including the use of cytology where indicated. (2) Adequate cytology and pathology services for the interpretation of speci mens. (3) Consultation service for referring cases for definitive diagnoses and recommendations for treatment. Six references are given. Author's summary 853 An Oral Cancer Detection Center. S. J. Shackner. Health News 41, 10-13 (April, 1964). This paper has attempted to show how an Oral Cancer Detection Center can be set up, how it operates and how it functions. The Center provides a central facility in a rural area for case finding, case referral, and professional and public education in oral cancer detection and control. Through the establishment and operation of similar centers, it is hoped that the profession will be motivated and oriented to utilize the diagnostic aids at its disposal. The private practitioner will become more aware of cancer control and realize the advantages of early detection by doing an oral cancer detection examination whenever a patient visits his office. This will eventually make every office an oral cancer detection center which is the^ one and only way to conquer the problem of oral cancer. There are 10 references. -- Author's summary 854 The Educational Program for Dentists and Physicians (For Detection of Oral Cancer). M.A. Engelman, Health News 417 16-19 (April, 1964). "1 ' The primary objective of an Oral Cancer Detection Center is the early detection of oral lesions so that the cure rate is increased, the need for disfiguring surgery decreased, and the number of deaths from cancer of this site reduced. A secondary objective of the Center is professional education for dentists and physicians, including residents and internes, stressing thorough oral examinations and exfoliative cytology. A final objective is the education of the general public in the prevention, detection, and treatment of oral cancer. There are 15 references. -- Author's summary 855 Epidemiological Consequences of an Arsenic-Lung Cancer Theory. R..W. Buechley. Am. J. Public Health 53, 1229-1232 (Aug. 1963). The world-wide lung cancer epidemic associated with cigarette smoking may be explained by an epidemiological chain showing excess lung cancer at each step leading from arsenic-high mines and smelters through arsenical insecticides, to lead arsenate spray residues on cigarette tobacco. If arsenic is a major causative carcinogen, the reported situations are only the known examples of many other situations consequent on the predicted by an arsenic-lung cancer theory. These consequences fall into two classes: (1) Predicted high lung cancer rates should appear in those persons whose work, or residence, is in arsenic, high situations. This list includes miners, smelters, smeltermen's wives and children, in secticide workers, agriculturists using arsenic sprays and processors and users of sprayed products--including cigarette smokers. (2) Lung cancer rates should be lower than one would expect among those whose work, or residence, is in arsenic-low situations no matter what the oth pollutants. This list includes all the populatione listed above, given that the mine, smelter, or insecticide is arsenic-free. It also includes cigarette smokers whose smoking is, and has been, confined to arsenic.free tobacco, such as is used in South Africa. -- APCA Absts. 856 A Review of 995 Cases of Primary Carcinoma of the Lung. R. W.Haber. Med. J. Australia 1. 5^1 (April 11, 1964). Of 995 eases of carcinoma of the lung reviewed, the anaplastic type was present in nearly 50% and the squamous variety in 38%; 88% of all cases occurred in men. The peak incidence was in the 51 to 70 years age group.) More cancers occurred in the right lung than io the left, and more occurred in the upper than in the lower lobes. The prognosis was worse in women and in the aged. It was better for lower lobe cancers in the right lung than for those ucc 6. 002731 4 vented tube from each engine blows air at very high pressure and forces gravel away from the engine intake. Other operating problems include temperatures that are 50F to 60F be low zero, 60-roph winds, and total dark ness in December and January in the High Arctic. Engines on airstrip equip ment such as trucks and snowplows are not turned off from Dec. 1 to Mar. 15. Though the regionals, too, face fuel problems, all are predicting revenue in creases this year. They see their big gest growth potential in scheduled pas senger service, although no one is scoffing at the big bucks to be made in hauling drilling equipment-and beerto oil teams in the Arctic or to the offagain, on-again $6-billion James Bay hydroelectric project In northwestern PWA ships cattle to the Orient and oil-drilling equipment to the Arctic Quebec. Nordair dies there from Mon treal, and. Quebec*ir operates cargo- only service. . Cattle plane. In the eyes of many indus try observers. Pacific Western is the best run of the regionals. Its fleet con sists of seven Boeing 737s, with three more on order, plus two 727s, two long- range 707s, five Convair 640s, four Her cules jet-prop freighters, and a few fly ing boats, pwa's operations range from its scheduled passenger services to shipping cattle to the Orient and ex tensive relief work in such places as Ni geria and Bangladesh. Scheduled pas senger services account for roughly 65% of pwa's revenues, charters for about 10%, and cargo services for the 'remaining 25%. Its cattle plane is typical of pwa's willingness to provide specialized ser vices to meet special needs. A conven tional Boeing 707-320C,'the plane can be equipped with either 13 stalls hold ing about 85 1,000-lb. cattle or double- tiers of pens that will-accommodate a great many more smaller animals. Donald N. Watson, pwa president, says that the plane has carried as many as 700 cattle from Toronto to Athens. The real keys to profits for pwa and the other regionals, however, have . been jets and charters. The jets boosted available seat-miles on routes with good load factors, and the. char ters gave the carriers the capability to use their aircraft more economically. Keith Miller, executive vice-presi dent of Eastern Provincial Airways, estimates the seat-mile cost on a- 100- passenger 737 at 2.2C a mi, compared with 5.54 for each mile on the 41-seat Handley Page Heralds the 737s are re placing. The break-even load factor on the jets is 42%, vs. about 80% on the prop planes. "The stimulation of a 737 is very substantial," Miller says. TECHNOLOGY industry's latest cancer scare The deaths of five workers in ten years seem linked to working on the plastic Federal officials met last week with plastics industry executives in Cleve land and Washington to try to deter mine whether the industry has un knowingly been exposing some of its 6,500 blue-collar workers to fumes that can lead to a rare form of liver cancer known as angiosarcoma. The focus was on 28 of the 42 plants in the U. S. that make vinyl chloride or use it to produce polyvinyl chloride resin (pvc), one of the most common plastics. The hearings grew out of the deaths of four workers over the last six years at a B. F. Goodrich Chemical Co. plant in Louisville, Ky. They could ultimately bring costly new rules for the PVC in dustry, whoee resins are used in such items as pipe, floor tile, phonograph records, and latex wall paints. "Im provements in work practices will probably require a 100% increase in the work force," says Walter B. Connolly, Jr., labor counsel for Firestone Tire & Rubber Co., which operates pvc plants in Pottstown, Pa., and Perryville, Md. In any case, the current pvc hulla baloo is certain to spark new demands by organized labor for closer exam ination of the possible long-range ef fects on workers of oth$r industrial chemicals. "The cancer took 15 to 20 years to develop," says one federal epi demiologist. Other chemicals could have similar "latency" periods, he says, so there could be more eruptions in the years ahead. "I hope we're not seeing the beginning of a health collapse." The vinyl chloride case is not the chemical industry's first encounter with osHA over carcinogenics. Last May the agency invoked emergency standards for 14 chemicals (bw-- May 19, 1973). Final rules for these mate rials went into effect last week, though, both industry and labor are suing for judicial review. The prospect of new, petrochemical versions of such health time bombs, as "black lung" and mercury poisoning, makes plastic industry leaders shudder. And indeed, new data presented at the standing-room-only osha hearing by Italian researcher Ceaare Maltoni. of Bologna's Institute of Cancer, leave little doubt that vinyl chloride is car cinogenic-at least to rats. H e exposed__ 67 rats to air containing 250 parts per million of vinyl chloride off and on for 52 weeks. By the end of 127 weeks,_ Maltoni reported, two had contracted angiosarcoma and nine contracted otheFIorros of cancer. Many chemlcaF industry executives had ~5owngra?ed~ the importance of earlier animal test results because the dosages were mas- A solvent that crippled chemical workers Laat August, Thomas F. Meade, 22, zeroed in on an ink solvent, methyl was stricken with a nerve disease after butyl ketone, used in applying decora- two years of work at Columbus Coated tive patterns, as the most likely culprit Fabrics Co., a subsidiary of Borden, While continuing to monitor the Inc., in Columbus, Ohio, that makes vi- plant's air, they banned the use of MBit nyl-comted fabrics for luggage and wall The plant's managers have switched to coverings. The disease, diagnoeed as a substitute, improved ventilation, is- periphera! neuropathy,, left Meade sued respirators to print shop workers, crippled, sad today ha wears leg and. moved lunch areas away from braces. He is the most severely af- work areas. faded of some 130 workers at the plant ' But Corwin Smith, president of Lo- who have suffered symptoms of the dis- cal 487 of the Textile Workers Union of ease. The lesser symptoms include America, which represents the plant's weakness and loss of coordination. workers, is not satisfied. He says that When the symptoms became wide- 26 members are still out with the dis- spread last summer, state health offl- ease, that eight of them are severely rial* tested the nerve responses of the- crippled, and that three workers whose plant's 1,124 employees and told 200 of condition improved are now sick again, them to stay home for two months. ~ On Feb. 9, the local struck the plant as Many others stayed- home, too, out of- negotiations collapsed on a new con- fear. By December, most employees trad; one of the union demands was a had returned, and many who had "proper work environment." Says showed neuropathic symptoms(ap- Smith: "People here don't know peared well again. whether they will be crippled in the fu- Meanwhile, Ohio health officials had ture or not." , I ' ; * j : i j 100 BUSIXSSWEK. Fmw,a. 1974 TECHNOLOGY ucc 002732 sivt>. on tne order to 5,000 to 30,000 ppm limit recommended since 1972 by nors, Jr., general manager of the Plas PPm- the American Conference of Govern tics Div. of Diamond Shamrock Chem The bombshell. The cancer crisis hit the ment Industrial Hygienists. In 1970, ical Co., which also observes that limit, vinyl industry just a month ago. Not- Italian researcher Dr. P. L. Viola re "there are not enough fumes in the air _ ing an unusual number of liver ail ported that rats exposed to heavy doses to smell." Where concentrations are ments among the Louisville plant of vinyl chloride developed malignant higher, he says, "we have ordered our workers, B. F. Goodrich physicians ran tumors. Several European chemical men to wear gas masks." blood tests last fall on the 271 workers companies banded together to support Vinyl fumes arise partly from leaks in the plant's FVC facility'and found 55 research by Maltoni, and in the U. S., in pipes and valves. But another likely with apparent liver abnormalities. The the Manufacturing Chemists Assn, be source is the polymerization vessels, company reviewed medical and insur gan to discuss an industry-wide re when they are opened for cleaning and ance records and by Jan. 16 had discov search program. A year ago, the MCA maintenance. NIOSH officials are con ered three deaths since 1971 that were set up an animal test program that will centrating now on the polymerization attributable to angiosarcoma. Federal not be completed until late 1975. The process, but they plan to extend their . health officials estimate the annual association also contracted with Taber- studies eventually to monomer produc death toll in the U.S. from this rare sbaw-Cooper Associates, of Berkeley, tion, as well as pvc fabrication and form of cancer at only even consumer use of PVC about 20. On Jan. 29 fur products. ther review by Goodrich Since safe limits for vi turned up a 1968 death nyl chloride are unknown, (two more cases, includ NIOSH is emphasizing safe ing a 1964 death, were work practices rather identified this week). than arbitrary concentra The company's top tion limits. Its recommen . management had already dations for the Louisville decided on public disclo plant, for example, in sure. It reported the situ clude such things as over ation to the National In head cleaning, daily show stitute for Occupational ers and clothing changes Safety & Health and to for workers, and ex the Kentucky Labor Dept panded air monitoring. It also began notifying Pinning n down. Goodrich's employees in all of its vi Louisville plant uses nyl chloride and PVC oper about 50 different chem ations, and it sent a re icals, and there is no proof lease to the press. "We of a direct link between are doing our utmost to vinyl chloride and the .express our real and liver cancer cases. But serious concern," says niosh officials are certain . John J. Bell, the com that the link exists, and pany's public affairs direc A B. F. Goodrich safety inspector uses a chemical "sniffer" to check the mca's Johnson con tor, "and yet prevent any whether vinyl chloride fumes are leaking from a polymerizing reactor. cedes that "vinyl chloride - undue panic." is the material of primary . NIOSH, which had immediately sent Calif., to check the available death suspicion." Only two other carcinogens, />- experts to Louisville, held a briefing records of workers at other vinyl arsenic and thorium-2S2. are provyen. early last week in Cleveland to tell plants. "So far," says Kenneth John causes of angiosarcoma, and medical i/ A management and labor leaders in the son, MCA technical director, "the results records on the four Goodrich workers industry what it knew about the car haven't been subjected to statistical, showed no exposure to~either. cinogenic effects of vinyl chloride. And analysis." Both niosh and industry officials on Friday, many- of the same execu To Dr. Irving J. Selikoff, the history hope, though, that the link is peculiar tives showed up in Washington for the shows that "our approach to the prob- to Goodrich's Louisville plant. Says . OSHA hearing. The federal agency will - - determine whether the situation war NIOSH hopes that the NIOSH Director Marcus M. Key: "We still hold to the possibility that the rants either an emergency standard or cause is a combination of cause could be a combination of two or at least a start on the regular rule- factors at only one plant making process. - three things acting together in the manufacturing process." , - The attitude of organized labor was lem was, shall I say, leisurely." Seli The Louisville plant is Goodrich's - a major concern. Anthony Masxocehl, koff, director of environmental medi oldest pvc plant and, unlike most legislative director of the Oil, Chemical cine at New York City's Mount Sinai . newer plants, is enclosed. It also has a & Atomic Workers, who attended the School of Medicine, has been a frequent number of older workers on the line. NIOSH briefing, says: "It's apparent criticof industrial health practices, and Some workers may have been affected we're dealing with a carcinogen. We one chemical executive calls his re by an epidemic of hepatitis that swept want to reduce exposure to zero. But mark, made at the OSHA meeting, the city a few years ago. A number of we have a wait-and-see attitude right "hindsight." other rubber and chemical plants, and now." Belatedly or not, some pvc producers their fumes, are located nearby. And While the fatalities at Louisville have been tightening up their oper the plant is one of the few that uses vi- came as a shock to the industry, vinyl ations. Goodrich, for example, says it nylidene chloride as a copolymerizing chloride has been suspect for a long had already done, or was doing, most of agent. Rudolph Jaeger, a physiologist time. Some 15 years ago Dow Chemical the things NIOSH recommended after at the Harvard School of Public Health, Co., based on its own studies, adopted visiting the Louisville plant, including told the osha meeting that test data an average exposure limit of 50 ppm sticking to a 50-ppm average exposure appear to point to that chemical, too, as for its workers--well below the 200* limit. "At 50 ppm," says Harry Con a carcinogen. _ TSCHNOLOGY ' BUSINESSWEEK; Ftbiuaiy S3.1974 ` 101 ucc 002733 Chemical Safety Data Sheet SD-56 PROPERTIES AND ESSENTIAL INFORMATION FOR SAFE HANDLING AND USE OF VINYL CHLOHIDS Chuailcnli hi any fttm an ba infaly itaad, handlad or und If tha phytical, (hamkal and haxordaut papartla* an fully undar> load and tha naauary pmaawllani, including tha uu *f pnpnr afagiwd* and pananat pntactiuu nquipmaat,, an abiacvad. REVISED 1972 MANUFACTURING CHEMISTS ASSOCIATION 111) CONNECTICUT AVENUE, N. W. WASHINGTON, 0. C. 20009 ucc 002734 i > $ht SD44 Manufacturing Chemists Association Vinyl ChfoHd 3. HAZARDS 3.1 HEALTH HAZARDS (See Section 10 MEDI CAL MANAGEMENT) 3.1.1 The primary hazard of vinyl chloride is associated with excessive respiratory exposure. Ex posure to high levels may produce some lung uritatioa. Chronic overexposure may produce liver injury. When inhaled it acts primarily as an anesthetic. The odor is pleasant to most individuals and, therefore, acutely 'dangerous levels may be easily tolerated. 3.1.2 'Warning Properties The lowest concentration of VCM at which its - odor~can be detected is reported to be 260 ppm. Olfactory tatiaue, however, may occur and the sense of sm-*n cannot be relied upon as a warning for ex cessive low grade exposures. 3.2 FIRE AND EXPLOSION HAZARDS 3.2.1 Vinyl chloride is a gas at normal atmos pheric temperature and pressure. The gas will bum very readily in proper mixtures of air or oxygen. An explosion hazard can exist when drawing samples or venting to the atmosphere. Open flames, local hot spots, friction, any spark producing equipment, and static electricity are to be avoided when handling this material. 3.2.2 Combustion Products of Vinyl Chloride Monomer Analysis of a combustion gas sample obtained immediately above a flame of vinyl chloride monomer burning in air shows presence of hydrogen chloride (27,000 ppm), carbon dioxide (58,000 ppm), car bon monoxide (9,500 ppm) and phosgene less than 10 ppm. Only in the very near vicinity of a VCM fire would significant amounts of phosgene be present. The main sources of danger to personnel result from the massive formation of hydrogen chloride gas and from carbon monoxide. However, the pungent odor of hydrogen chloride acts as a warning to clear the area or to obtain the necessary breathing ap paratus before attempting any fire control measures. See MCA Chemical Safety Data Sheet, SD-39, Hy drochloric Acid (Aqueous) and Hydrogen Chloride (Anhydrous). 3.3 STABILITY HAZARDS Vinyl chloride is shipped and used in both the in hibited and uninhibited state. In the uninhibited state, high purity must be maintained since contami nants may catalyze polymerization or cause decom position of the VCM, liberating hydrogen chloride. Prior to shipment, uninhibited VCM should be tested for stability under shipping and storage conditions. Cleanliness of shipping containers is of prime im portance when shipping uninhibited VCM. Vinyl chloride may polymerize as a result of ex posure to air, oxygen or sunlight at ambient or higher temperatures. Vinyl chloride does not form peroxides by autoxidation as readily as many other monomers. In the absence of an initiator, VCM is chemically quite stable. Commercial VCM, uninhibited, is stored and shipped in steel containers under conditions which avoid exposure to air and sunlight. For large volume, long term storage, refrigeration is sometimes employed to maintain the temperature at about 20* C., maximum, to minimize the formation of haze, a condition caused by a small degree of polymeriza tion. 4. ENGINEERING CONTROL OF HAZARDS 4.1 BUILDING DESIGN Equipment and vessels containing VCM should preferably be isolated from other facilities by walls and floors of fin resistive construction. Standard fire wails are recommended for the iso lation of larger equipment and storage tanks, while partitions of plaster on expanded metal lath may be used to isolate smaller equipment from other com bustible materials. Not less than two means of exit should be provided from each separate room or building in which VCM is stored, handled or used. No portions of. such a room or building should be farther than 75 feet from the nearest exit. Additional exits should be provided depending upon the number of persons in the build ing. (See NFPA Standard #101 Life Safety Code.) All exit doors should open out in the direction of travel and should be provided with panic hardware. Fire doors should open out in the direction of travel and be of an approved type. Operations where large quantities of VCM are used should preferably be. housed in one story build ings. j 6` .... ......... . . ucc 002735 Vinyl Chloride Manufacturing Chemists Association Mofiva! Sht SD-54 available to man the lifeline and to assist in the rescue if needed. The rescuer should be in view of the outside attendant at all times or in voice com munication with him. 8.5 EXTERIOR REPAIR WORK All outside welding, burning or spark-producing work on tanks or equipment which have contained VCM should be done after the container has been thoroughly cleaned of VCM vapors. Purging should be tested by a competent person to see if it is free of VCM. It is not recommended that air be used to purge a vessel. If the repair work is interrupted, the tank atmos phere should be checked thoroughly and a new work permit issued before resumption of work. 9. WASTE DISPOSAL (See 7.5) 9.1 All Federal, State, and Local regulations re garding health and pollution should be observed. Disposal of waste material, however, depends to a great extent upon surroundings, weather conditions and the emergency making disposal necessary. 9.2 When it becomes necessary to dispose of VCM as such, it is preferable to do so as a vapor, venting to an area free of any source of ignition. 9.3 When a waste disposal problem arises as a result of a major spill or equipmeat rupture, only properly protected and qualified personnel should remain in the area. 9.4 Waste mixtures containing VCM should not be allowed to enter drain or sewers as serious explosions in such systems may result. 10. MEDICAL MANAGEMENT 10.1 HEALTH HAZARDS 10.1.1 Vinyl chloride monomer does not present a serious industrial health hazard provided workers are adequately supervised and observe the proper means of handling it. Under the Occupational Safety and Health Act, the CIS. Department ot Labor has set a 500 ppm Ceiling Value on permitted employee exposures. Based upon animat and human observa tions. this level 'provides considerable margin ot _safetv for industrial exposures. Note: A syndrome termed occupational acroosteolysis, characterized primarily by Raynaud's phenomenon and osteolytic changes in certain bones, particularly the distal phalanges of the hands, has been noted among certain workers in vinyl chloride polymerization operations. The specific cause of this disease, and particularly any role played by vinyl chloride, is unknown. .Recent research studies reported from Italy in dicate mat repeated, long-term high level exposures ot rats to vinyl chloride monomer vapor can result in the development of malignant tumors. However. . many years of industrial experience with human ex posures to concentrations frequently tar above cur rent standards have not demonstrated any carcmogentettv to humans. 3 10.1.2 Acute Toxicity Levels on the order of 6,000 ppm for five minutes exposure are required to produce minimal symptoms resembling mild alcohol intoxication in humans. Levels approximately 16,000 ppm for the same length of time will produce varying degrees of intoxication, with light-headedness, some nausea, and a dulling of visual and auditory responses in most humans. 10.1.3 Chronic Toxicity The liver is the principal target resulting from excessive chronic exposure. The currently recom mended ceiling level (OSHA) of 500 ppm is well below a level producing any signs or symptoms of toxicity. 10.2 PREVENTIVE MEASURES 10.2.1 All operations in which vinyl chloride is used should be regularly evaluated and' atmospheric concentrations kept, at all times, below 500 ppm. Sophisticated air sampling techniques are required. This includes gas chromatography. Processes must be closed or ventilated sufficiently to achieve a con centration control low enough so that respiratory rotection devices are needed only on an emergency asis. 10.2.2 Personal Hygiene Vinyl chloride should be kept off the skin and out of contact with the eyes. If accidental contact to the skin occurs, immediate washing with soap and water is necessary; if to the eyes, immediate irrigation 17 UCC 002736 Manual Sht SM* Manufacturing Chemists Association Vinyl Chloridi for a minimum of 15 minutes with water is required. The peseoce of skin and eye washing equipment in the areas where vinyl chloride is used is necessary. Washing supplies and equipment should be maintained and always immediately available. 10.2.3 Physical Examinations Preplacement examinations should be made on all workers having potential exposure to vinyl chlo ride, with particular emphasis placed upon liver and kidney functions. 10.3 SUGGESTIONS TO PHYSICIANS Treatment for vinyl chloride intoxication is symp tomatic; no special procedures are required. It should be recognized that the principal target of chronic exposures is the liver, with secondary effects, particularly in acute exposures, to the kidney. In acute overexposures the primary effect is on the central nervous system. Note to Physician: Avoid use of epinephrine or related drugs in treating acute overexposure cases since vinyl chloride may sensitize the heart to the arrhythmic action of these drugs. 10.3.1 Oxygen Administration Oxygen has been found useful in the treatment of inhalation exposures of many chemicals, especially those capable of causing either immediate or delayed harmful effects in the lungs. In most exposures, administration of 100% oxygen at atmospheric pressures has been found to be adequate. This is best accomplished by use of a face mask having a reservoir bag of the non-rebreatbing type. Inhalation of 100% oxygen should not exceed one hour of continuous treatment. After each hour, therapy may be interrupted. It may be reinstituted as the clinical condition indicates. Some believe that superior results are obtained when exposures to lung irritants are treated with oxy gen under an exhalation pressure not exceeding 4 cm. water. Masks providing for such exhalation pressures are obtainable. A single treatment may suffice for minor exposures to irritants. It is believed by some observers that oxygen under pressure is useful as an aid in the prevention of pulmonary edema after breathing irritants. In the event of an exposure causing symptoms or in case of a history of severe exposure, the patient may be treated with oxygen under 4 cm. exhalation pressure for one-half hour periods out of every hour. Treatment may be continued in this way until symp toms subside or other clinical indications for inter ruption appear. CAUTION: It may not be advisable to ad minister oxygen under positive pressure in the presence of impending or existing cardiovascular failure. The use of adrenalin is not recommended because some chlorinated hydrocarbons can increase the risk of ventricular fibrillation after adrenalin therapy. 11. FIRST AID 11.1 GENERAL PRINCIPLES First aid should be starred at once in case of acute intoxication with vinyl chloride. Immediately re move the affected individual to fresh air. Refer all injured individuals to a physician and give a detailed account of the incident. 11.2 CONTACT WITH SKIN AND MUCOUS MEMBRANES Vinyl chloride, in concentrated form, is a skin irri tant. All contaminated clothing should be removed at once; and this clothing, including shoes, if there is any evidence of contamination, should not be worn again until thoroughly dry. All affected skin areas should be thoroughly'washed with warm water and soap. The individual should be referred to a physi cian. 11*3 CONTACT WITH EYES If vinyl chloride has entered the eyes, prompt washing with copious quantities of water for at least 15 minutes should be instituted immediately. It is advisable to irrigate the eyes gently with water at room temperature in order to minimize additional pain and discomfort. Prompt medical attention should be obtained. 11.4 INHALATION Promptly remove the affected individual from ex posure, to fresh air. If breathing has ceased effective artificial respiration should be started immediately. If oxygen inhalation equipment is available oxygen should be administered, provided a person authorized for such administration by a physician is available. The patient should be comfortably warm but not hot. Stimulants will rarely be necessary where adequate oxygenation is maintained. Any such drugs for shock treatment should be given only by the attending physician. Never attempt to give anything by mouth to an unconscious patient. 18 ucc 002737 U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE PUBLIC HEALTH SERVICE ucc 002738 SURVEY OF COMPOUNDS WHICH HAVE BEEN TESTED FOR CARCINOGENIC ACTIVITY Supplement; I By Philippe Shubik The Chicago Medical School Chicago, Illinois and Jonathan L. Hartwell National Cancer Institute National Institutes of Health Bethesda, Maryland 1957 v' ucc 002739 1 \ jr * r )><. I'evomie j f 1. Oppcnhetiser et cl., 1952 Ant mill 45 rota 1 Strain or type Ulster Beit PrvpnraUtMi mat ilnce 240.--VINYL CHLORIDE POLYMER SUo nnd I1HJ U* -(CHjCHCl) - Film s.c. 247. t-VINYL PROPIONATE CH3CH3COOCH=CII3 Antmulu villi tUMOttJ flu rv 1 vn L ur* 471 Tumora*** 44 alive at 189 d. Over 22 aos. Ambrose, 1950a 'Ik. 1 -r. Hodge et al., 1952a 5 rata 45 rata Doga 40 rota Albino Albino F 0.64J In the diet F 0.05 - 2.50* P.0. P.0. 248.- -ZINC DIMETHYLMTHIOCARBAHATE Znf-S-CS-NfCHj^Ij -- Rochester -- 3 op 25 ag* por kg* t? cepaulc dolly for X mo. U1F 0.01 - 0.5*ln the diet P.0. P.0. 0 0 0 0 -- -- 392 d. 223 d. 100f 1 no. 1 VO. Sulth, Jr., et al., 1953 i 200 rota 240. --ZINC ETHYLENE BISDmnOCARBAKATE 2" Albion IttF 500 10,000 p.p.n. In the diet (CH3)2{NH-CS-S-)3Zn P.0. 100 rata 9 dogs Albino Afcmgrel IBP 500 10,000 p.p.ai. In the diet--- 20 - 10,000 p.p.a, in the diet P.0. P.0, 0**o o*** o** Sacrificed at various Intervals X d. 13 died by 52 vka. 2 yrs. 1004 1 yr. *** 14 sorccama, 12 fibrosarcomas, 1 liposareaeu, 1 unclassified malignancy. FIrat >4i 9 lung tumors, 1 adrenal tumor, 1 smell boeal tutor, 1 mammary carcinoma and tutor at 189 day*. 1 adenocarcinoma of thyroid In 100 treated rata. Conatdered spontaneous. 2 lung * uarketed aa Wthone Z78. tuners in 20 controls. ,i' ,t0 10 rata at the 10,000 p.p.a. level had thyroid hyperplasia. 242 10,000 p.p.a. Induced thyroid hyperplasia. ' I t i! i