Trichlorethylene: AReview · Trichlorethylend been used for angina pectoris, crushable ampoules for...

Brit. J7. industr. Med. i966) 23, 249

Trichlorethylene: A ReviewG. F. SMITH

From the Medical Branch, H.M. Factory Inspectorate, Bristol 8

The physical and chemical characteristics of trichlorethylene are discussed together with its uses inindustry and medical practice. Chemical and physical methods of the estimation of trichlorethylene in airhave been described, including the use of gas detector tubes, which today is the method most commonlyemployed.The metabolism of trichlorethylene was systematically investigated by Butler (1948), who in animals

established the identity of the main metabolites appearing in the urine, Powell (I945a, b) having also donethis in human subjects. The excretion of these metabolites has since been repeatedly investigated, but theintermediate breakdown products within the body as well as the organ mainly responsible still remainuncertain.The acute toxicity of trichlorethylene, manifested preponderantly by central nervous system effects,

came to be recognized during the second decade of this century, not long after its introduction as a substitutefor benzol as a degreasant in Germany during the First World War. The recognition of a possible chronictoxic effect, characterized by a mild psycho-organic syndrome, came much later and is still not universallyaccepted. Damage to the trigeminal nerve after closed-circuit trichlorethylene anaesthesia was observedsoon after its introduction as a general anaesthetic 30 to 40 years ago, and it was shown to be due to break-down to dichloracetylene in carbon dioxide absorbers. The pure substance seems otherwise not to have aspecific effect on this nerve. The balance of opinion, based on human observations and on animal experi-ments, is against a severe toxic effect on the liver, although individual cases of liver damage in industrialworkers have been reported. The sudden fatal collapse of young workers during mild exercise has on rareoccasions been described, there being in most cases an element of heavy exposure. Investigations on manand animals indicate that pure trichlorethylene has no severe effect on other systems of the body.Maximum permissible levels for trichlorethylene in air were reduced from 400 p.p.m. in I947 to 200

p.p.m., and in I96I there was a further reduction to ioo p.p.m., which, except in the Soviet Union, is atpresent accepted in most parts of the world.

Trichlorethylene, CHC1 :G.C12, has a boilingpoint of 86°C., a melting point of -87-IC., and aspecific gravity of I.47 at Is54°C. At room tempera-ture it volatilizes readily as its vapour pressure ishigh and its latent heat low. Its vapour is heavierthan air, and it smells like chloroform.

Chemical Characteristics

One great advantage in industry is its lack offlammability, since trichlorethylene forms com-bustible or explosive mixtures with air only at hightemperatures (4Io'C.), but it will become flammablein oxygen-enriched atmospheres at lower tempera-tures (Jones and Scott, 1943). Thermo-decomposi-tion may readily occur at I20°C., or even lower,

especially in the presence of catalysts, such as finelydivided aluminium, or on exposure to ultra-violetlight; the second of these is preventable by storagein the dark, in dark-coloured bottles, or in cans.Hot flames or glowing surfaces may cause break-down to phosgene (Ministry of Labour BookletNo. 8) but, in the presence of catalysing metals orwhen under pressure, more complicated productssuch as dichloracetyl chloride or hexachlorbenzenemay be produced (Stiiber, 193i). A more usualproduct is hydrochloric acid, acid-accepting stabi-lizers such as triethylamine, ethylenediaminehydrate, thymol, benzylamine, and even petrol andammonia having been used to prevent its formation.Trichlorethylene does not react with cold inorganicacids but decomposes violently in hot nitric acid.It reacts more readily with alkali, explosive chlor-acetylenes being formed. Humphrey and McClel-

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land (i944) showed that at 370C. trichlorethylenedecomposes readily in carbon dioxide-absorbingcanisters containing soda lime, with the productionof dichloracetylene, which oxidizes readily to phos-gene and carbon monoxide. Although trichlor-ethylene is poorly soluble in water, it is freelymiscible in a wide range of other solvents and dis-solves gums, plastics, and a wide variety of fats andoils.

Industrial Significance

Manufacture Trichlorethylene is produced bythe chlorination of acetylene and is separated fromthe tetrachlorethane, also produced, by fractionation(Riegel, 1949). It has many synonyms such asAlyglen, Blacosolve (U.S.A.), Cecolene, Cecosolve(U.S.A.), Chlorylen (Germany), Crawshawpol(paints), Dukeron (paints), Fleckflip, Lanadin (woolcleaning), Lithurin, Perm-a-chlor, Petzinol (gal-vanizing), Trethylene, Triclene, Triklone (U.K.,trichlorethylene-soaps), Vitran, and Westrosol, etc.Current British Standards specifications and UnitedStates patents lay down permissible standards ofpurity for various technical grades based on specificgravity, distillation temperature, alkalinity, moisturecontent, and freedom from contaminants.

Uses in Industry Its versatility, relativechemical stability, non-flammability, volatility, andpoor solubility in water make trichlorethylene a veryuseful solvent. Spain (I965) estimated that thereare at least 50 applications in which it may causehazard. The commonest of these is degreasing, forwhich it was first used in Germany as a substituteduring the First World War (Weitbrecht, I965). Ithas found particular use for metal degreasing as apreliminary to plating, anodizing, and painting,having replaced the inflammable benzol formerlyused. The commonest type of degreasing tank is anopen vat, fitted with condensing coils to prevent theescape of fumes and more recently with lip extrac-tion to limit 'drag-out': less frequently, fully en-closed and automatic degreasers for standardizedprocesses are used, and the use of cold solvent forbench degreasing is not uncommon. It has manyother uses, some already superseded, namely as arefrigerant, as a vehicle in silicone parting agents inshell moulding (Tubich, Davis, and Bloomfield,I960), printing inks, paints, lacquers, varnishes, gasand tar purification, as a vehicle for adhesives, andfor drugs, chemicals, and perfume manufacture.' Itis being replaced in dry cleaning and in solventsoaps by perchlorethylene (Combey, I965). As ittakes up substances ofhigh molecular weight withoutreacting with them, it is useful for fat extraction,

wax extraction from cotton, and for impregnation.Its bactericidal properties have been used in eggpreservation, insecticides, and hair-washes. Since ithas a stable viscosity, it has been used in lowtemperature research (Imperial Chemical In-dustries).

Medical Uses

Trichlorethylene is supplied for medical purposesunder the name Trilene (or Trimar) in Great Britainand Trethylene in the United States of America.The standards of purity laid down in the BritishPharmacopoeia (I963) allow o-oi% by weight ofthymol preservative and not more than o-ooi% of ablue dye, used to distinguish it from chloroform; itmust be free from chloride, free chlorine, phosgene,acid, and non-volatile matter.

Anaesthesia Usually given in combinationwith gas and oxygen, this is its main surviving usein medicine. It was introduced into Great Britainabout 30 years ago, as a general anaesthetic, follow-ing recommendations made by Hewer (1942, I943)and Hewer and Belfrage (1938) about I0 years afterits introduction into the U.S.A. Although it hasbeen said to have many of the characteristics of anideal anaesthetic by Striker, Goldblatt, Warm, andJackson (I935) and Wagner (1946), it has a limitedworking range, good muscular relaxation beingdifficult to achieve. Its non-flammability enables itto be used with an electrical cautery (Hunter, I964).The very low incidence of adverse effects on thevital organs reported by Ostlere (I948), in a reviewof 40,000 cases, underlined its low toxicity comparedwith chloroform, said to produce a similar type ofanaesthesia (Hewer, I942; Johnson, 1945). The useof trichlorethylene in closed-circuit apparatus wasabandoned in I944 after the danger of dichlor-acetylene formation had been recognized (Lancet,I944a; Morton, 1943; Hunter, I944).

Analgesia It is commonly used as an analgesicin obstetric practice as a o.5% mixture with air, asrecommended by the Medical Research Council inI954 (British Pharmaceutical Codex, 1963; ExtraPharmacopoeia, 1958). Following reports ofanaesthesia in the distribution of the sensory root ofthe trigeminal nerve in trichlorethylene workers, theuse of trichlorethylene inhalations as an analgesicfor trigeminal neuralgia was introduced by Plessner(igi6a, b). Later experience and experimental workshowed, however, that this treatment was non-specific and largely ineffective (Oljenick, I928;Krantz, Carr, Musser, and Harne, I935; RubinsteinPainter, and Harne, I939). Trichlorethylene has

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Trichlorethylend

been used for angina pectoris, crushable ampoulesfor inhalation being listed in the British Pharma-ceutical Codex (I963). Ellis and Bryce Smith (I965)have successfully used trichlorethylene inhalationsto relieve the pain of post-operative breathingexercises.

Its use as an abreaction reagent in psycho-analysis was described by O'Connor (I954).Trumper, Thelwall Jones, and Taylor (1936)reported on its superiority over ether and spirit as awound cleanser. Its earlier use as an anthelminthicwas mentioned by Lande, Dervillee, and Nun (I939).

Determination of Trichlorethylene in Air

Chemical Methods Formerly trichlorethylenewas commonly determined by estimation of thechloride released by either combustion or hydrolysis(Tebbens, I937; Elkins, Hobby, and Fuller, 1937;Alford, I947; and Pernell, I944). For indirectmethods, absorption media such as amyl acetate,alcohol or silica gel have been proved efficient(Elkins et al., 1937; Goldman and Seegmiller, 1943;Forssman and Holmquist, I953), but direct com-bustion methods, described by Tebbens (1937) andDudley (I941) for field surveys, have been equallyuseful. Buchwald (I965) stated that gas detectortubes developed over the last 20 years (Gisclard,I960; Drager and Drager, 1957) could not beaccurate to more than ±220%, an objection met byKitigawa (I96I) by means of a special calibrationmethod. The discovery of the pyridine reaction byFujiwara in I9I4 (von Oettingen, 1937, I964) andindependently by Ross (I923) laid the foundationfor this commonly used method, which replacedless reliable colorimetric tests (Cole, I926). Tri-chlorethylene, when heated with pyridine and alkali,forms a glutaconaldehyde of a characteristic colour,the intensity of which is proportional to the testconcentration; Webb, Kay, and Nichol (I945) andBruning and Schnetka (I933) found that substances,such as chloroform, with three chlorine atomsattached to one carbon in the molecule react themost sensitively. Measurement is mostly spectro-photometric at the optimum wavelength of 430 m ,u.Earlier workers relied solely on direct visual com-parison either with known solutions or with fuchsin-in-water standards prepared beforehand (Webb etal., 1945; Barrett, I936; Bruning and Schnetka,1933; McCollum, I930).The use of multiple units for fluid absorption

media was found by Elkins and his colleagues (I937)not to produce the calculated 20% increase inefficiency. With suitably designed single or doubleunits, collection rates of 70 to 8o% have been ob-tained (Elkins et al., I937; Barrett, I936). Similar

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efficiencies have been provided by silica gel ab-sorbers (Forssman and Holmquist, I953; Hickish,Smith, and Bedford, I956; Fahy, I948). For con-centrations of 90 to 340 parts of trichlorethylene permillion of air, a rate of flow through the absorptionapparatus of one to two litres per minute was foundby Pernell (I944) and by Webb and his colleagues(I945) to achieve collection rates of about 90%.

Physical Methods With the exception ofhalide detector lamps (Ministry of Labour, S.H.and W., Booklet No. 8), physical methods areaccurate, although complicated and requiring ex-pensive apparatus. Gas interferometers and ioniza-tion detectors, used often in conjunction with gaschromatographs, can be used for trichlorethylene,some instruments providing continuous analysis(Giever and Cook, I960; Harrold and Gordon, 1939;Keenan, I960; Talvitie, I958; Patty, I939;Andreatch, I962). Applicable methods based on thedirect measurement of vapour partial pressures havealso been described (Kay, Reece, and Drinker, I939;Couchman and Schulze, I939; Silverman, Reece,and Drinker, 1939). Hunter (I949) devised aningenious and simple method, relying on the dis-placement by trichlorethylene vapour of a knownvolume of air. Morgan and Duxbury (I965)described a method of radioactivation analysis, inwhich -Q8C produced by irradiating trichlorethylenesamples was measured. The expected error of gasinterferometers may be as low as o0oI (Patty, 1939),and an accuracy of about Ooi to 0o02 can be ob-tained with ionization detector instruments. Morganand Duxbury (I965) did not detail the accuracy ofactivation analysis but they found that the minimaldetectable amount of chlorine was i mg. Accuraciesof 98% were obtained with vapour pressure instru-ments by Kay et al. (1939) and Couchman andSchulze (I939).

Metabolism

Absorption The lungs are by far the mostimportant route, absorption through the skin beinggenerally regarded as negligible (Malkinson, I960;Lande et al., I939); McCord (I932) and Gonin andFraisse (I947), however, thought that transcutaneousabsorption was possible. Human experiments haveshown 50 to 6o% retention of trichlorethylene(Teisinger, I96I; Bardodej and Vyskocil, 1956;Soucek and Vlachova, I960; Bartonicek, I962;Ahlmark and Forssman, I95Ia, b) but retentioncalculated from industrial exposures, namely byGrandjean, Munchinger, Turrian, Haas, Knoepfel,and Rosenmund (I955), was 70%.By equilibration experiments with trichlor-


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ethylene-air mixtures on whole blood, plasma,washed cell suspensions, haemoglobin solutions,and water, Powell (1945b, I947) concluded that thegreater part of trichlorethylene uptake in the bloodis by haemoglobin in the erythrocytes. In herearlier investigations, Powell (I945a) showed thatarterial blood contained more trichlorethylene thanvenous blood and that it had largely left the bloodfour days after exposure. Transplacental passage oftrichlorethylene was demonstrated by Helliwell andHutton (I950). Estimation of trichlorethylene up-take of artificial plasmas, representing only theaqueous and fatty contents, showed that absorptionis almost certainly dependent on their protein con-tent and certainly dependent on their fat content.Fabre and Truhaut (I952) suggested, without ex-perimental evidence, that the lipids in the erythro-cyte membrane of rats absorbed trichlorethylene.Accumulation of trichlorethylene in fatty tissue inman was suggested by Bartonicek and Teisinger(I962) and Clayton and Parkhouse (I962). Genevois(I936) suggested that in mice the rate of uptake oftrichlorethylene in the water content of tissues wasprobably in direct relationship to the vapour con-centration, resulting in the slower absorption ofsubstances of higher molecular weight. The dura-tion of exposure influenced the distribution of tri-chlorethylene in animal tissues, the lungs containingthe most after acute exposures, whereas organs suchas the gonads and spleen contained a larger amountafter chronic exposures (Bruning and Schnetka,I933; Fabre and Truhaut, 1952). In dogs, fat wasfound to be the tissue which retained trichlor-ethylene the longest (Barrett, Cunningham, andJohnston, 1936).

Metabolic Breakdown Estimates of theamount oftrichlorethylene metabolized after absorp-tion made by Teisinger (I96I), Soucek and Vlachovi(I960), and Bartonicek (I962) varied in humanexperiments between 72 and 8o%. Trichloraceticacid in the urine after trichlorethylene exposure wasdemonstrated by Powell (I945a) in human subjectsand in dogs by Barrett and Johnston (I939), whoalso showed the presence of chloroform in theseanimals. Butler (I948, 1949c) demonstrated tri-chlorethanol, present as a glucuronide, after theadministration of trichlorethylene and chloralhydrate.

Studies using isolated tissue slices, from dogs(Butler, I949b), have shown that no particularorgan is responsible for trichloracetic acid produc-tion and, from rats, that the spleen and lungs (Fabreand Truhaut, I952) and not the liver were mostactive. Precursors during the oxidation to end-metabolites were first postulated by Barrett et al.

(I936), and intermediates, some rather improbable,such as unsymmetrical tetrachlorethane (Barrett andJohnston, I939), the toxic and unstable trichlor-ethylene oxide (Powell, I945a), and, more com-monly, chloral hydrate (Bardodej and Vyskocil,I956; Ahlmark and Forssman, i95ia, b), have beensuggested, but as yet none of these substances hasbeen demonstrated. Bartonicek and Teisinger(I962) have shown that trichloracetic acid and tri-chlorethanol are probably formed separately fromchloral. Monochloracetic acid together with hydro-chloric acid may arise directly by splitting of thedouble bond of the trichlorethylene molecule(Bardodej and Vyskocil, I956). From controlledexposures in man, it has been shown that betweenI9 and 3I % of absorbed trichlorethylene appears astrichloracetic acid, and the ratio of trichloracetic acidin milligrams per litre of urine to trichlorethylene inparts per million of air varies between 2:I and I :I(Teisinger, I96I; Soucek and Vlachova, I960;Bartonicek, I962) according to the degree of expo-sure. Industrial exposures have yielded lowervalues, namely 5 to I3 % of trichloracetic acid withratios of trichloracetic to trichlorethylene varyingbetween i *6:i and 3:1 (Rivoire, Genevois, andTolot, I962; Friberg, Kylin, and Nystr6m, I953;Frant and Westendorp, I950; Elkins, I96I). Grand-jean and his colleagues (I955) stated that good cor-relation between the two values could be obtainedin trichlorethylene workers only if the exposure ratewere used rather than trichlorethylene concentra-tions, and they quoted a 3 to i relationship. Theoutput of trichloracetic acid and trichlorethanol infaeces, sweat, and saliva was too small to influencethese values (Bartonicek, i962).

In man and animals, the greater proportion of thetrichlorethylene retained appears as trichlorethanol.Estimates of 35 to 45 % were obtained in humanexperimental exposures (Teisinger, I96I; Soucekand Vlachova, I960; Bartonicek, I962) and of 22 to45% in laboratory animals (Lob, I960; Bartonicekand Soucek, I959). Teisinger (I96I) found thatmonochloracetic acid accounted in man for 30% ofthe trichlorethylene retained, whilst Soucek andVlachova (I960) put this at 4I%.

Distribution of Metabolites within theOrganism Since plasma contained 4-8 times lesstrichloracetic acid than red cells, from which itcould be removed only by elution, Bartonicek (I962)concluded that erythrocytes selectively absorb thismetabolite. A similar selectivity was found in ratsby Fabre and Truhaut (I95I, I952), but Bartonicekand Soucek (I959) considered that, in rabbits, tri-chloracetic acid was more firmly bound to serumalbumins. Paykoc and Powell (I945) demonstrated

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Trichlorethylene: AReview2that, when injected, trichloracetic acid was excretedat the same rate as if formed by the metabolism oftrichlorethylene, since it diffused rapidly into extra-cellular fluid where it remained. The opposing viewthat metabolites traverse cells seemed to be sup-ported by the demonstration by Bartonicek (I962)of their excretion in saliva, sweat, and faeces. Theunchanged excretion rate of trichloracetic acid afterinjection indicated, to Soucek and Vlachov'a (I960),its fixation on to protein in the erythrocytes andplasma. Fabre and Truhaut (1952) found that, afteracute exposures, the largest amount of trichloraceticacid was found in the spleen, whereas after chronicexposures the largest amount was in the lungs.After trichlorethylene anaesthesia, Powell (I945a)found that maximal concentrations of trichloraceticacid in blood occurred in about 48 hours, tailing offto low values in seven to I2 days, according to thedose; peak plasma levels of trichlorethanol occurredsomewhat earlier, namely, five to 24 hours afterinhalation, according to Butler (I949a).

Excretion of Unchanged TrichlorethyleneThrough the lungs, this was found to start atmaximal levels and was complete within 24 tO 48hours (Powell, I945a; Bartonicek, I962; Ahlmarkand Forssman, I95ib), but substances which in-hibit the metabolism of trichlorethylene, such asdisulfiram, increased pulmonary excretion by threetimes. Urinary excretion has been found to be veryslight in man (Powell, I945a; Teisinger, I96I;Bruning and Schnetka, I933) and in animals (Fabreand Truhaut, I952; Forssman and Holmquist,I953).

Excretion of Metabolites Bartonicek (I962)showed that blood, at its peak level, contains 5-2times more trichloracetic acid than urine. Aftersingle inhalations, it is first excreted within one ortwo hours (Barrett et al., I936; Ahlmark andForssman, I95Ia, b) or in I2 to 24 hours, as foundby Powell (I945a). Maximum urinary levels usuallyoccur after 48 hours (Powell, I945a; Soucek andVlachovia, I960; Ahlmark and Forssman, I95Ia;Bartonicek and Soucek, I959). Rather earlier peakswere found by Barrett and his colleagues (I936), andafter trichloracetic acid by mouth, as reported byAhlmark and Forssman (I95Ia). Peaks tended tooccur later after trichlorethylene ingestion, as foundby Bardodej and Vyskocil (I956), and after thegassings reported by Mikiskova and Mikiska (I960)and by Friberg and his colleagues (I953). In animals,maximal levels appeared within two to three days(Bartonicek and Soucek, I959; Barrett et al., I936;Friberg et al., I953; Ahlmark and Forssman, 195 Ia).The overall rate of decline to minimal urinary levels

was regarded by Soucek and Vlachova (I960) as thesum of two exponential rates, with half-periods ofexcretion of 50 tO 70 hours. The total period ofexcretion was between I0 and I4 days, as found bySoucek and Vlachovat (I960), Bartonicek (I962),Ahlmark and Forssman (Ig5Ia), and Powell (I945a),the latter having stated that changes in blood andurine trichloracetic acid levels follow a roughlyparallel course. Prolonged excretion rates wererecorded after leaving industrial exposure by Rivoireand his colleages (I962). Trichlorethanol is excretedthrough the lungs in man for about four days afterexposure (Bartonicek, I962), and it appears as a glu-curonide in the urine (Butler, I949c) within one totwo hours, reaching maximum levels, roughly twicethose of trichloracetic acid, in 24 hours, after whichthere is an exponential decline to the lowest levelsin I2 to I4 days (Bartonicek and Soucek, I959;Butler, I949a; Bartonicek, I962; Mikiskova andMikiska, I960; Soucek and Vlachova, I960). Thehalf-period of excretion of the two rates was foundby Soucek and Vlachova (I960) to be 24 and 40hours. Monochloracetic acid appears in the urinea few minutes after the beginning of exposure,reaches maximal levels in four to five hours, andfalls to the minima exponentially in about four days(Soucek and Vlachova, I960), there being only oneexcretion phase with a half-period of about i5 hours.The relationship between trichloracetic acid and tri-chlorethanol in human and animal urine was foundto vary between I :2-4 and I:3, but since the two havedifferent rates of excretion, the time of samplingafter exposure will materially influence the result(Bartonicek, I962; Soucek and Vlachova, I960;Bartonicek and Soucek, I959).

Determination of Trichlorethylene andMetabolites in Biological Media The collectionof expired air for trichlorethylene estimation neces-sitates collection apparatus designed to avoidresistance to expiration (Powell, 1945a; Bartonicek,I962; Bartonicek and Teisinger, I962). Forssmanand Holmquist (I953), using rats, estimated residualtrichlorethylene in the exposure chamber aftermaking a correction for absorption by fur. Tri-chlorethylene in blood, pulped tissue, or urine hasbeen removed with a current of air by Powell (I945a,I947), Fabre and Truhaut (i95i, I952), andKulkarni (I944) or with steam distillation byBruning and Schnetka (I933), Barrett et al. (I936),and Habgood and Powell (I945). In all cases, esti-mation was done by the pyridine reaction. Brainand Helliwell (I949), who followed Rogers and Kay(1947), developed a more sensitive single-phasepyridine reaction for the estimation of trichlor-ethylene in blood samples. Trichloracetic acid is

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separated from protein in blood and tissues byprecipitation with sodium tungstate. The super-natant fluid is filtered off and its trichloracetic acidcontent is estimated by the pyridine reaction, whichhas replaced earlier colorimetric methods describedby Levine and Bien (I934); this reaction is used alsofor the determination of trichloracetic acid in faeces,sweat, saliva, and urine (Soucek and Vlachova, I960;Bartonicek, I962; Ahlmark and Forssman, I949;Forssman and Ahlmark, I946; Powell, 1945a;Fabre and Truhaut, I952; Butler, I948). Trichlor-ethanol glucuronide in urine is first hydrolysed withacid and then oxidized to trichloracetic acid, aswhich it is estimated (Soucek and Vlachova, I960;Butler, I949a; Weitbrecht, I965). From plasma, theglucuronide must first be extracted with heptane(Butler, I948) before being estimated in the sameway. Soucek and Vlachov'a (I960) estimated mono-chloracetic acid in urine by a paper chromatographicmethod.

Toxicity of Trichlorethylene and Metabolites

Acute Toxicity The opinion expressed byUllmann in 1914 (Calvet, Planques, Ribet, and Coll,I959) that trichlorethylene is non-toxic has longsince been abandoned in view of increasing evidenceto the contrary. The contributory role played bybreakdown products, particularly in most industrialgassings and closed-circuit anaesthesias, may haveconfused the issue in some cases. Trichlorethyleneand similar substances have been thought to have aneffect on cell metabolism at the water-fat interphase,particularly relevant in the case of nervous tissue, toa degree proportional both to its coefficient of distri-bution between water and fat and to its vapourpressure (Genevois, I936). Slight metabolic changesoccur in about 20% of anaesthesias with trichlor-ethylene (Hewer, I942; Ostlere, I948). Using suchcriteria as narcosis, body weight changes, and tissuehistology, Carpenter, Smyth, and Pozzani (I949) andAdams, Spencer, Rowe, McCollister, and Irish(I95I) found that the acute vapour toxicity of tri-chlorethylene was low in animals, being about halfthat of carbon tetrachloride and the same as that oftoluene. Genevois (I936) demonstrated increasingtoxicity with increasing chlorination of the ethylenichydrocarbons. This was not, however, found byJoachimoglu (I921), who used fish swimming inaqueous solutions of these solvents. Most workershave found that perchlorethylene is rather moretoxic than trichlorethylene. Death in acute over-whelming exposures is most commonly due torespiratory and cardiac failure, although there is awide difference between the minimum narcotic andfatal doses. Less frequent causes of death have been

pulmonary oedema due to inhalation of phosgene,produced as a thermal breakdown product of tri-chlorethylene vapour (Spolyar, Harger, Keppler, andBumsted, I95i), and liver failure where con-taminants or unassociated medical conditions maycontribute.

Chronic Toxicity This has been thought to benon-existent, rare, or doubtful (Lloyd Potter, 1958;Johnstone, I94I; Ministry of National Health andWelfare, Canada, I949), but there is increasingopinion that chronic toxicity may be more importantthan acute (Lachnit and Rankl, I950; Moeschlin,quoted by Browning (I965); Borbely, quoted byMerewether (I956)), the nervous system again beingparticularly affected. Women are said to be moresusceptible than men. Rare cases of sudden deathshortly after leaving work, thought to be due toheart failure, have been described. Bartonicek(I960) found negligible changes in rabbits exposedto trichlorethylene over long periods.

Acute Exposures and the Central NervousSystem The cardinal symptom of gassing is un-consciousness, carbon dioxide excess and oxygenlack in confined spaces probably contributing insome cases (Hamilton and Johnstone, I945; Mere-wether, I956; Longley and Jones, I963). Prenarcosischaracterized by mild excitatory symptoms has beendescribed in industrial over-exposures by Lob(I960), Carrieu and Marc (I926), and by Barrett andhis colleagues (I936). Bardodej and Vyskocil (1956)stated that narcosis proceeds in two stages, the dura-tion of which is related to the degree of exposure.After recovery, contaminants may contribute to suchmanifestations as prolonged headache, as describedby Cotter (I950) and Chalupa, Synkova, andSecevik (I960), or cerebral irritation, resemblingthat of encephalitis with hallucinations as describedby Cotter (I950) and the Chief Inspector ofFactories (I939). Alterations in the electro-encephalograph have been described by Desoille,Pinchon, Lille, and Bourguignon (i962b) andChalupa and his colleagues (I960), who found thatthey lasted longer after solvent than after carbonmonoxide poisonings and were often accompaniedby characteristic changes in the various componentsof memory. Organic damage to the cerebrum andcerebellum have been described by Bardodej andVyskocil (1956) as the results of gassing. In animalsreceiving pure trichlorethylene, Adams et al. (I951)reported that the only important acute effect wasnarcosis, from which recovery without sequel wasthe rule, and before that there occurred a prenarcoticphase, similar to that in man. Desoille, Pinchon,Jans, and Bourguignon (i962a) found that trichlor-

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ethylene caused electro-encephalographic changes inrabbits similar to those of epilepsy, which could beincreased by prolonged alcohol dosage before expo-sure. Potentiation of the effects of trichlorethyleneby small doses of carbon monoxide was demon-strated by Forssman, Gernandt, and Goldberg(I948), even after elimination of carboxy haemo-globin from the blood. Grandjean (I960) demon-strated the suppression of inhibition responses inrats after single exposures at concentrations down to200 p.p.m. The effects of drinking trichlorethylenedo not differ materially from those of gassing;unconsciousness may come on more quickly andit may last longer, even up to three days, periods upto 36 hours, however, being more usual (Stentifordand Logan, 1956; Todd, I954; Teare, I948; Calvetet al., 1959). Delay in onset of narcosis may occurdue to a full stomach (Naish, 1945), or alcohol maypotentiate the effects (Chief Inspector of Factories,1953), but in the case described by Stephens (1945)habitual taking of alcohol was thought to havecaused resistance. Excitatory phenomena afterdrinking trichlorethylene, possibly contributed toby contaminants, have been described by Matruchot(1944-I945), Todd (I954), and Calvet and hiscolleagues (1959).

Excitement during the first and second stages oftrichlorethylene anaesthesia has been reported(Hewer and Hadfield, I94I; Hewer, I942, 1943;Striker et al., I935). Many causes for convulsionsunder trichlorethylene have been suggested, as byPask (I942). Under closed-circuit anaesthesia, di-chloracetylene formation has been postulated as apossible factor by Garland (1942) and Condon(I948), although they have been described only inassociation with respiratory arrest by A. R. Hunter(I944) and Bernstine (I954). Surgical stimulationunder light anaesthesia appeared to have been thecause in the case, described by Culbert (1942), thatreceived open trichlorethylene. Therapeutic inhala-tions of pure trichlorethylene produced abnormali-ties of the electro-encephalogram in the case ofGeiger (I943). In animals receiving pure trichlor-ethylene, Desoille et al. (i962a) and Carrieu (I927)thought that convulsions were an anoxic effect.Post-anaesthetic headache is usually transitory andinfrequent (Hewer and Hadfield, 1941), the severecase of McAuley (1943) probably having been dueto dichloracetylene. In rare instances, confusionalstates have been caused by the potentiation of tri-chlorethylene by hexabarbitone, used for induction(D. Hunter, I944). Dichloracetylene was probablythe cause of the brain damage described in the caseof Humphrey and McClelland (i944) and in thatdescribed in the Lancet (I944a).

Chronic Exposure and the Central NervousSystem Some of the symptoms attributed toacute poisoning feature also in chronic poisoning.Grandjean et al. (I955) found a significant incidenceof fatigue, headache, loss of memory, intolerance toalcohol and tobacco, and of depression, in order offrequency, among degreasers; although they re-garded these as typical, they could find no correla-tion between the frequency of subjective complaintsand the degree of exposure. Frant and Westendorf(1950) attributed this difficulty to the habituationeffect of long exposures. Weitbrecht (I965) andBardodej and Vyskocil (I956) did find such a cor-relation for lengths of exposure of over I0 years.Objections to reliance on subjective complaint werepartly met by Ahlmark and Forssman (I95ib), whoaccepted only severe and typical complaints, associ-ated with a high urinary trichloracetic acid output.The testing of memory, intellect, and concentrationof degreasers enabled Grandjean and his colleagues(I955) to demonstrate a mild psycho-organic syn-drome characterized by slowing of thought, per-severation of ideas, difficulties of attention, andemotional changes. Bardodej and Vyskocil (I956)found a similar effect based on tests of attention, andTrense (I965) suggested that such tests might beused for the screening of degreasers for chronicpoisoning. No unexposed controls were used by anyof the above workers, except that Ahlmark andForssman (195ib) made comparison with statisticsprovided by the Swedish Occupational Hygiene andHealth Department. Most workers have found acorrelation between symptoms and the urinary tri-chloracetic acid level, but observations by Frant andWestendorf (1950) and reports by the Chief Inspec-tor of Factories (1959, I960) demonstrated no suchrelationship, and Bardodej and Vyskocil (I956)thought that urinary trichloracetic acid was a poorindex of chronic intoxication. Behaviour changes inrats after prolonged exposures to pure trichlor-ethylene were investigated by Battig and Grandjean(I963). They found depression of neuromuscularactivity and reduction of fear inhibition. Trichlor-ethylene has an addiction risk, Stuber (I93I) havingfound I2 cases among 284 intoxications. A back-ground of mental instability largely accounted forthe hypomanic changes sometimes seen in such cases(O'Connor, 1954).Headache has been considered to be the earliest

sign of chronic intoxication by McCord (I932),Baader (I927), and Wurm (I93I). Vertigo has beenreported to be characteristic by Kleinfeld andTabershaw (I954) and by the Chief Inspector ofFactories (I952, I960); O'Connor (1954) and Hewerand Hadfield (I94I) thought that impurities were

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likely to be the cause. Tiredness and sleepinesscome on typically at night after leaving work (Hickishet al., I956; Isenschmid and Kunz, I935b), but theymay be alternated with insomnia at weekends, asmentioned by Lachnit and Rankl (I950). These twosymptoms have been generally accepted to accountfor suppression of libido. Bardodej and Vyskocil(I956) found insignificant changes in I7-ketosteroidoutput, and Lachnit and Rankl (I950) found none.Intolerance to alcohol, typified by flushing of theface and dizziness after small quantities, wasdescribed by Lachnit and Rankl (I950), Grandjeanand his colleagues (I955), and Bardodej andVyskocil (I956).

Effects on Peripheral Nerves The neuritisdescribed by Stuber (I93I) in German industrialworkers is now thought to have been due to im-purities. Many recent surveys in industry haveindicated possible damage to both spinal and auto-nomic nerves, similar effects having been producedin animals exposed to pure trichlorethylene byAdams and his colleagues (I951).Of the 284 cases reviewed by Stuber (I931), there

were nine of visual disturbances, including retro-bulbar neuritis, possibly also present in the casesdescribed by Isenschmid and Kunz (I935a, b),Plessner (i9i6a), Baader (I927), and the ChiefInspector of Factories (1952). Slight swelling of theoptic disc has been thought typical by Oljenick(I928) and Kramer (I92I) in cases receiving thera-peutic inhalations, and by Jackson (I934) inanaesthesia cases. None of the surveys on industrialworkers revealed this condition.

Anaesthesia of the sensory endings of thetrigeminal nerve in trichlorethylene workers has beendescribed by Stuber (I93I), Bardodej and Vyskocil(I956), Baader (I927), and Plessner (i9i6a). Treat-ment early this century of trigeminal neuralgia bypure trichlorethylene inhalations appeared toachieve a high success rate (Plessner, i9i6a; Seelert,1922; Hildesheimer, I92I; Rubinstein, I937), butmost later reports were less encouraging, particularlyin chronic cases (Kramer, I921; Blumenthal, I924;Glaser, 193i). The experimental evidence ofBlumenthal (I924), the observations during anaes-thesia by Jackson (I934) and Hewer (I942, I943),and by Oljenick (I927) during treatment by inhala-tion indicated no specific effect on this nerve. Theresults of faradic stimulation of the fifth nerve ofdogs given trichlorethylene by Rubinstein et al.(I939) supported the view that pain was relieved bygeneral analgesia or sedation. The two cases ofpermanent relief of trigeminal neuralgia describedby Eichert (I936) could not, however, be explainedeither by contamination or generalized analgesia.

Goldblatt and Goldblatt (I956) stated that anosmiawas characteristic of chronic poisoning, and damageto other cranial nerves has been reported by James(I963), Isenschmid and Kunz (I935b), and Plessner(i9i6a). Damage to the fifth nerve by trichlor-ethylene anaesthesia has been attributed to dichlor-acetylene (Enderby, I944; Morton, I943), andHumphrey and McClelland (I944) excluded thepossibility of a neurotropic virus as a cause. Elam(I942) found no case among I,000 patients. Effectson other cranial nerves after industrial gassings havebeen reported by Lachnit and Rankl (1950) and afteranaesthesia by Striker and colleagues (I935),Humphrey and McClelland (I944), and Carden(I944). Hill (I966) described exposure to accumu-lated breakdown products, possibly including tri-chloracetylene, resulting in fatal paralysis of themuscles of the neck, face, throat, and respiration. Intwo other milder cases, numbness of the face was aresidual symptom.

Chronic Exposure and the AlimentaryTract Anorexia, nausea, vomiting and intoleranceto fatty foods have been regarded as chronic gastro-intestinal effects in trichlorethylene workers byRivoire et al. (I962), Ahlmark and Forssman(I95Ib), Stuber (I931), Challen and Hickish (I963),and Trense (I965). Grandjean and his colleagues(I955) thought that malfunction of the autonomicnervous system was a contributory factor. Bardodejand Vyskocil (1956) found no significant incidencein their subjects.

Severe damage to the liver resulting fromindustrial exposure is uncommon (Browning, I952,1959) and is thought to occur only after heavy ex-posure, toxic breakdown products possibly con-tributing (Derrick and Johnson, I943; Willcox,1934a, b). Acute massive necrosis was found byJoron, Cameron, and Halpenny (I955) and by Priestand Horn (I965), no non-occupational factor havingbeen discovered. Investigation of groups of workershas indicated a disturbance of fat metabolism and afailure of the esterification of cholesterol accordingto Guyotjeannin and van Steenkiste (I958) andOllivier (I944-1945), and slight changes in liverfunction tests have also been described by Lachnitand Rankl (I950) and Trense (I965). Slightly in-creased levels of serum glutamic oxalacetic acid andaldolase in those exposed at work have been shownby Lachnit and Pietschmann (I96I) to occur only ifthey had received beforehand doses of alcohol justbelow that amount required to produce a rise inunexposed controls; this seemed to indicate thattrichlorethylene is likely to be hepatotoxic only inthose who habitually take alcohol. Others under-taking the investigation of trichlorethylene workers

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have found no evidence of liver dysfunction. Seifter(I944) produced hepatic insufficiency associatedwith slight histological changes in dogs exposed topure trichlorethylene at intensities resembling in-dustrial exposures, but Adams and his colleagues(I95I), Taylor (I936), and Carrieu (I927) producedonly congestion of the liver in animals exposed forlong periods.

Acute Exposure and the Alimentary TractVomiting has been reported after industrial gassings(Cotter, I950) but after anaesthesia it has mostlybeen attributed to dichloracetylene (Culbert, I942;McAuley, I943; Enderby, I944; Carden, I944),although Willcox (I934b) thought that, as withchloroform, this may be due to some degree of liverdamage. The incidence of post-anaesthetic vomit-ing, based on the observation of large numbers ofadministrations is low (Elam, I942; Griffiths, I942;Haworth and Duff, 1943; Gordon and Shackleton,1943). Gastro-intestinal irritation after ingestion,the purity of the trichlorethylene being mostly indoubt, has been said to be severe (Stephens, I945;Calvet et al., I959), but Matruchot (1944-I945) wasunable to confirm this by oesophagoscopy.

Liver damage after acute exposure is rare, and inmost cases there is the added possibility of eithercontaminants or some non-occupational factorhaving played a part. In the gassing cases withacute yellow atrophy reported by the Chief Inspectorof Factories (I930-I950) and by Carrie, Perrault,and Bourdin (194I), and in those of Cotter (I950)with functional disturbances, the part played bycontaminants may have been significant. Similarfactors may have been important in the casedescribed by Willcox (1934a, b). It has been sug-gested that the liver may be more at risk if trichlor-ethylene is absorbed through the portal system(Lande et al., I939). Kleinfeld and Tabershaw(1954) found some centrilobular necrosis andStentiford and Logan (I956) found mild dysfunctionin cases ofingestion. After anaesthesia, liver damage,considered rare by most anaesthetists, has been re-ported by Herdman (I945) after a prolonged closed-circuit anaesthetic undertaken for the plastic repairof an apparently healed septic wound, and by Dodds(1945) after an open administration in a woman withtoxaemia ofpregnancy. Two cases of fatty degenera-tion were reported in the Lancet (I944b). Dichlor-acetylene was found by Humphrey and McClelland(I944) to cause no more than slight hepatic necrosisin animals. Neither contaminants nor pre-existingliver disease accounted for the centrilobular necrosisin a 2-year-old child after a short open administra-tion reported in the Lancet (I944c). Even after tri-chlorethylene injections, Wirtschafter and Cronyn2

(I964) produced in animals peak serum glutamicoxalacetic acid levels only one tenth of those pro-duced by equivalent doses of carbon tetrachloride;there was also some mild parenchymatous degenera-tion. Glycogen depletion of liver cells was the onlychange produced by inhalation experiments on dogsand mice by Herzberg (I934) and Hunter (I949).Even after exposures of 6,400 p.p.m. given to micethere was no more than centrilobular fatty infiltra-tion, with no increase in extractable fat or changesin the serum ornithine carbamyl transferase activityas found by Kylin, Reichard, Sumegi, and Yllner(I962). Fiessinger and Laur (I936) and Fiessingerand Loeper (I94I) demonstrated in mice similarhistological changes, only one animal having ad-vanced to complete granular degeneration afterlonger exposure. The centrilobular changes, usualwith chlorinated hydrocarbons, were shown to bedue to a reduction of centrilobular circulation byGlynn and Himsworth (1948).

Effects on the Renal System Reports of renaldamage in industrial workers are rare. Investigatorswho have studied trichlorethylene workers havefound no significant incidence. Gutch, Tomhave,and Stevens (I965) reported a case of primary renaldamage and failure, confirmed by a needle biopsy, ina trichlorethylene degreaser, the retention of meta-bolites and possible contaminants due to oliguriahaving been corrected by intermittent peritonealdialysis. The chronic animal exposures to pure tri-chlorethylene of Seifter (I944), Carrieu (1927),Taylor (I936), and Adams and his co-workers (i95I)indicated either minimal or no effects. Lande et al.(1939) produced glomerulonephritis in animalsgiven oral doses over long periods. Renal damageafter gassing is rare and normally mild, slighttubular damage being the usual finding (Cotter,I950; Calvet et al., I959). Marty, quoted by Calvetand his colleagues (1959), described severe renaldamage after ingestion.

Effects on the Haemopoietic System Effectson the haemopoietic system are rare, althoughPatoir, Marchand, and Ducarne (1943) stated thatabnormal findings would be more frequent if bloodexaminations of workers were undertaken moreoften. This does not seem to be borne out by thenegative findings of most of those who investigatedgroups of trichlorethylene workers, only Bardodejand Vyskocil (1956) having found a io% incidenceof polycythaemia, thought to be due to marrowanoxia; a degreaser presenting with this conditionwas described by Patoir and his colleagues (I943).Slight anaemia in industrial workers has beenmentioned by Hickish and his colleagues (1956),

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Derobert (1944-I945), and Tara (1944-I945). Thetwo cases of aplastic anaemia described by Browning(I943) were thought probably not to-be occupational.Chronic exposure in animals seems not to causeblood changes (Seifter, I944; Carrieu, 1927; Adamset al., I95I).

Effects on the Cardiovascular SystemBradycardia and precordial pain have been reportedin groups of trichlorethylene workers by Bardodejand Vyskocil (I956), who attributed the brady-cardia to increased vagal tone. Similar findings withhypotension have been reported in gassings byCotter (I950), in cases of ingestion by Carrieu andMarc (I926) and Calvet and his colleagues (I959),and in dogs exposed to pure trichlorethylene byJackson (I934), the latter attributing this effect tocentral depression. Sudden death in young, ap-parently healthy people exposed at work, usuallyafter the end of a shift and during mild exercise, hason rare occasions occurred, as reported in the fivecases by the Chief Inspector of Factories (1938,1939, I952), in three cases by Kleinfeld andTabershaw (I954), in one case by Bell (i95I), andin an addict by James (I963). A similar case hasbeen reported by Trott (I966) in which exposuresof 400 p.p.m. had been found. Superimposed acuteover-exposure and the possible action of con-taminants cannot always be ruled out, and, in spiteof a lack of supporting pathology, these deaths havebeen thought to be due to syncope possibly associ-ated with increased adrenaline sensitivity (Weit-brecht, I965). Most cases suffered prolonged over-exposure. Foulger (I949) found in young peopleinhaling small quantities of chlorinated hydrocar-bons decreased pulse pressure, indicating a generalanoxaemia of the viscera, which could theoreticallylead to heart failure if the pulse were accelerated byeven gentle exercise. An anaesthetic death due toventricular fibrillation was described by Lloyd-Williams and Hewspear (1942), but reaction toadrenaline in a local anaesthetic, although improb-able, could not entirely be excluded. Bernstine(I954) reported syncope during analgesia in whichthere was surgical stimulation. Estimates of theincidence of irregularities of the pulse under anaes-thesia have varied between nil and 24% and haveoften been thought to be due to dichloracetylene(Culbert, 1942; Ayre, 1943; Gordon and Shackleton,1943; Striker et al., I935; A. R. Hunter, I944).Mallach, Marquardt, and Werch (I943) and Love(I937) noticed no fall in blood pressure after experi-mental and therapeutic inhalations. The coronaryarteriosclerosis ascribed to exposure in a degreaserby Gerbis (I936) could equally well be explained asan ageing effect. Slowing of conduction of the

cardiac impulse without myocardial damage inanimals has been produced by Marquardt, Mallach,and Werch (I943), and Mallach et al. (I943). Theslowing effect on isolated heart preparations but lackof effect on canine coronary flow were investigatedby Krantz, Carr, and Harne (1934) and Krantz et al.(I935); the lack of effect on isolated blood vesselpreparations was investigated by both these teamsof workers. Increased conduction time was foundin dogs by Waters, Orth, and Gillespie (1943), whoalso demonstrated abnormalities ofrhythm in humansubjects.

Effects on the Respiratory System Therespiratory tract is especially liable to the effects ofcontaminants and breakdown products. Thoseundertaking surveys of trichlorethylene workersfound no significant incidence of respiratorytroubles but Bardodej and Vyskocil (I956) and theChief Inspector of Factories (I946, 1952, 1953)found a significant incidence of mild congestivesigns. Nasal catarrh was stated by Goldblatt andGoldblatt (I956) to be typical of chronic irritation.Derrick and Johnson (I943) described the suddendeath of a dry cleaner just after leaving work andattributed it to pulmonary oedema due to the irrita-tion of breakdown products. The effects of con-taminants are more important in acute gassingswhen they may cause even fatal pulmonary oedemadue to phosgene derived from trichlorethylene as inthe case of Spolyar et al. (i95I). Exposures with aless obvious contaminant factor have caused acutetoxic but less severe lower respiratory irritation, asreported by Priest and Horn (I965), McCord (I932),Teare (1948), James (I963), Cotter (I950), Carrieuand Marc (I926), and Kleinfeld and Tabershaw(1954). No more than tachypnoea has been thefeature of some poisonings (Stentiford and Logan,I956), respiratory rate increases having occurred inanaesthesia as reported by Gordon and Shackleton(1943), but otherwise pulmonary complicationsseem few (Ostlere, I948; Striker et al., 1935). Thedecomposition of trichlorethylene to phosgene byburning tobacco is now thought to be unlikely (Brit.7. industr. Med., 1945) and Elkins and Levine (1939)showed experimentally that the breakdown to phos-gene by cigarettes and cigars is negligible. Acuteand chronic exposure of animals to pure trichlor-ethylene produced minimal pulmonary effects(Desoille et al., I962b; Adams et al., I951; Taylor,1936; Ahlmark and Forssman, I95Ib) but Lande etal. (I939) produced toxic pneumonitis in rabbitsrelatively easily.

Effects on the Skin and Eyes Trichlor-ethylene can act as a primary irritant and as a

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sensitizing agent; in the latter case there are rashesdescribed as either dermatitis, dermatoses, oreczema (Schwartz, Tulipan, and Birmingham,1957). Stuber (I93i) and Schwartz and RusseU(I94i) noted a significant incidence, possibly duepartly to contaminants, not found by later investi-gators of groups of degreasers. It has been sug-gested by Stuber (1931) that, due to its volatility,trichlorethylene may cause capillary damage, al-though this may be in doubt. Chemical burns fromcontact with the fluid have been reported by Carrieuand Marc (1926), Roche, Genevois, and Marin(I958), and Davenport (1951); Maloof (I949) andMcBirney (I954) described cases of burns with con-centrated vapour. Blistering with the pure liquidhas been produced in animals (McCord, 1932;Lande et al., 1939; Carrieu, 1927). Bardodej andVyskocil (I956) and Ahlmark and Forssman (I95 ib)considered that conjunctivitis was a feature of over-exposure; this was not, however, found by otherinvestigators. Anaesthesia ofthe cornea due possiblyto contact with vapour has been noticed in man byDesoille et al. (i962a) and Hunter (I957) and inanimals by Carrieu (1927). Conjunctivitis has beenreported by Rivoire et al. (I962), Carrieu and Marc(1926), and Stephens (1945).

Toxicity of Metabolites The toxicity of tri-chloracetic acid is low, it being only a very mildnarcotic (Powell, 1945a). Ahlmark and Forssman(I95Ia), comparing trichlorethylene with chloralhydrate, decided that trichloracetic acid was respon-sible for very little of the toxic effect of trichlor-ethylene. Marhold, quoted by Soucek and Vlachova(I960), and Woodard, Lange, Nelson, and Calvery(194I) showed that its LD50 for rats and mice waswell below that of the other metabolites, approxi-mately one tenth of that of trichlorethylene.Mikiskova and Mikiska (I960) found that depressionof the central nervous system in rabbits with tri-chlorethanol was greater than that with trichlor-ethylene. In a further paper (Mikiskova andMikiska, I966), these authors demonstrated that tri-chlorethanol depressed spinal reflex activity andmotor cortex electrical excitability at least five to sixtimes more than trichlorethylene, although there wasno qualitative difference in their pharmaceuticaleffects. Although it resembles tribromoethanol(avertin) chemically, Hewer and Belfrage (1938) andCase (I943) found that trichlorethanol had a moretoxic effect on the heart. Mikiskova and Mikiska(I966) showed that trichlorethanol decreased theheart rate in guinea-pigs to a much greater extentthan trichlorethylene: they observed a similaramplitude depression of the electro-encephalogramtracings in these animals early in trichlorethylene

anaesthesia. Bronchodilatation was demonstrated byAdriani and Rovenstine (I943) on isolated humanlung tissue. Marhold (Soucek and Vlachova, I960),Woodard et al. (194I) and Morrison (1946) foundthat monochloracetic acid has a toxicity greater thanthat of trichloracetic acid but rather less than that oftrichlorethanol. The keratolytic effect of trichlor-acetic acid has been mentioned by McLaughlin(1936) and Prosser White (I934).

Prevention and Treatment of PoisoningMaintenance of apparatus and proper workingmethods are the most important factors in the pre-vention of over-exposure (Ministry of Labour S.H.& W. No. i5; Silverman, I943; Witheridge andWalworth, I940). The Chief Inspector of Factories(I920-I965) and Stuber (I931) found that failure towork within the capacity of tanks and entry intothem without proper precautions accounted formany gassings. Hargarten, Hetrick, and Fleming(I96I) calculated an approximate frequency rate foraccidents among trichlorethylene workers, occurringmuch as described above, of 0o3 per million expo-sure hours over a io-year period. Difficulty in theinterpretation of the maximum allowable concentra-tion of trichlorethylene in the air and the maximumbiological concentration of trichloracetic acid in theurine may be due to the impracticability of dis-sociating the effects of acute and chronic exposures.Air concentrations together with urinary metabolitelevels are generally thought the best means ofmonitoring working conditions. Until 1957 inGreat Britain, Canada, and the U.S.A., the recom-mended safe level was 400 p.p.m. in air, after whichit was reduced to 200 p.p.m. for a 40- to 48-hourworking week. Teisinger (I96I) argued that such alevel would produce toxic effects if pulmonaryventilation were taken into account. In I96I, thelevel was reduced to i0o p.p.m., the currentlyaccepted level (Morgan, I964; American Con-ference of Govemmental Industrial Hygienists,i959; Council on Occupational Health, I965;Ministry of Labour S.H. & W. No. 8; British Chem-ical Industry Safety Council, I965) although somestates in North America had adopted this level aboutI946 (Flinn, I946). The current Soviet level of6 p.p.m. based on neurological tests (Barnes, I96I),has been considered nearest to the upper limit of40 mg. trichloracetic acid per litre of urine suggestedby Elkins (I96I), Grandjean and his colleagues(I955), and Ahlmark and Forssman (i95ib), butChallen and Hickish (I963) stated that 33 mg. perlitre already indicated over-exposure. In a laterpaper by Grandjean, quoted by Browning (I965),this level was raised to 96 mg. per litre. With theexception of those authors attempting mental testing

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(Grandjean et al., I955; Bardodej and Vyskocil,I956), the fixing of limits has largely been based onnoting the frequency of complaints, and no one hascompared his results with a matching control group.The assessment of exposure measuring unchangedsolvent in expired air was considered impractical byElkins (I954) and Ahlmark and Forssman (i95ib).The odour of trichlorethylene is first detectable atabout 6o p.p.m., although this threshold readily riseson continued exposure (Hargarten et al., I96I;Gutch et al., I965) and although the anaesthetic levelis usually thought to be about I0,000 p.p.m., cases ofgassing have occurred at lower levels (Longley andJones, I963). The exclusion of those with liver,neurological, psychological or cardiovascular dis-orders from working with trichlorethylene has beensuggested (Stiiber, I93I; Hunter, I957). The use ofprotective clothing to prevent skin damage and non-specific effects has been recommended (Desoille etal., I962a; Carrieu, I927; Schwartz et al., 1957), andpatch testing to exclude solvent sensitivity indermatitis cases occurring in the plastics industryhas been described by Malten and Zielhuis (I964).Emergency treatment for gassings follows standardlines, but Lloyd Potter (I958) stressed the avoidanceof stimulants containing adrenaline. Bartonicek andTeisinger (I962) suggested specific antidotes whichinhibit metabolism, such as disulfiram for severecases, fructose, or sodium lactate.

REFERENCES

Adams, E. M., Spencer, H. C., Rowe, V. K., McColister,D. D., and Irish, D. D. (I95I). Arch. industr. Hyg., 4,469.

Adriani, J., and Rovenstine, E. A. (I943). Anesthesiology, 4,253.

Ahlmark, A., and Forssman, S. (1949). Proc. gth int. Congr.industr. Med., London, 1948, p. 552.

and - (195ia). Acta physiol. scand., 22, 326.and (I95Ib). Arch. industr. Hyg., 3, 386.

Alford, W. C. (I947). J. industr. Hyg., 29, 396.American Conference of Governmental Industrial Hygienists

(I959). Arch. industr. Hlth, 20, 266.Andreatch, A. J. (I962). Arch. environm. Hlth, 4, 3I7.Ayre, P. (I943). Brit. med. J., I, 489.Baader, E. W. (1927). Zbl. Gewerbehyg., 14, 385.Bardodej, Z., and Vyskocil, J. (I956). Arch. industr. Hlth,

13, 58 IBarnes, J. M. (I96I). Brit. med.J., 2, I097.Barrett, H. M. (1936). J. industr. Hyg., I8, 34I.

Cunningham, J. G., and Johnston, J. H. (I936). Ibid.,21,479.

and Johnston, J. H. (1939). J. biol. Chem., 127, 765.Bartonicek, V. (I960). Arch. Gewerbepath. Gewerbehyg., IS,

317.- (I962). Brit. J. industr. Med., I9, I34.

and Soucek, B. (I959). Arch. Gewerbepath. Gewerbehyg.,17, 283.

and Teisinger, J. (I962). Brit. J. industr. Med., 19, 2I6.Battig, K., and Grandjean, E. (I963). Arch. environm. Hlth,

7, 694.

Bell, A. (I95 I). N.Z. med.J7., 50, I I9.Bernstine, M. L. (I954). Arch. Surg., 68, 262.Blumenthal, F. (I924). Dtsch. med. Wschr., 50, 140.Brain, F. H., and Helliwell, P. J. (I949). Biochem. J., 45, 75.British Chemical Industry Safety Council (I965). Quart.

Safety Summary, 36, 25.British Journal of Industrial Medicine (I945). Editorial

comment, 2, I67.British Pharmaceutical Codex (I963).British Pharmacopoeia (I963).Browning, E. (I943). J. industr. Hyg., 25, 124.-(I952). Toxicity ofIndustrial Organic Solvents, Med. Res.

Coun., Industr. Hlth Res. Bd, Rep. No. 8o, p. I69.(I959). Brit. J. industr. Med., i6, 23.(I965). Toxicity and Metabolism of Industrial Solvents,p. I89. Elsevier, Amsterdam.

Briining, A., and Schnetka, M. (I933). Arch. Gewerpath.Gewerbehyg., 4, 740.

Buchwald, H. (I965). Trans. Ass. industr. med. Offrs, I5, Ioo.Butler, T. C. (I948). J. Pharmacol. exp. Ther., 92, 49.- (I949a). Ibid., 97, 84.

-(I949b). Ibid., 95, 360.(I949c). Fed. Proc., 8, 278.

Calvet, J., Planques, J., Ribet, A., and Coll, J. (I959). Arch.Mal. prof., 20, 297.

Carden, S. (I944). Brit. med.J., I, 3I9.Carpenter, C. P., Smyth, H. F., and Pozzani, U. C. (1949).

J. industr. Hyg., 31, 343.Carrie, P. A., Perrault, M., and Bourdin, J. S. (I94I). Arch.

Mal. prof., 3, 345.Carrieu, M. F. (I927). Rev. Hyg. Mid. prev., 49, 348.- and Marc (I926). Presse mid., 34, I199.

Case, E. H. (I943). Anesthesiology, 4, 523.Challen, P. J. R., and Hickish, D. E. (I963). Brit. J. industr.

Safety, 6, 92.Chalupa, B., Synkova, J., and Secevik, M. (I960). Brit. J.

industr. Med., 17, 238.Chief Inspector of Factories (I920-I965). Annual Reports.Clayton, J. I., and Parkhouse, J. (I962). Brit. J. Anaesth., 34,

141.Cole, W. H. (I926). J. biol. Chem., 71, I73.Combey, W. (I965). Publ. Hlth Inspector, 73, 706.Condon, H. A. (I948). Brit. med. J., 2, 340.Cotter, L. H. (I950). Arch. industr. Hyg., I, 319.Couchman, C. E., and Schulze, W. H. (I939). J. industr.

Hyg., 21, 256.Council on Occupational Health, A.M.A. (I965). Arch.

environm. Hlth, 10, II5.Culbert, T. D. (I942). Brit. med. J., 2, 679.Davenport, H. T. (I95I). Brit. J. Anaesth., 23, 56.Derobert, L. (1944-1945). Arch. Mal. prof., 6, 32I.Derrick, E. H., and Johnson, D. W. (1943). Med. J. Aust.,

30 (2), 355.Desoille, H., Pinchon, R. A., Jans, M., and Bourguignon, A.

(I962a). Arch. Mal. prof., 23, 693.-,-, Lille, F., and Bourguignon, A. (I962b). Ibid.,

23, 5.Dodds, G. H. (1945). Brit. med. J., I, 769.Drager, H., and Drager, B. (1957). Information on the Drager

Gas Detector. Dragerwerk, Lubeck.Dudley, H. C. (I94I). Publ. Hlth Rep. (Wash.), 56, 102I.Eichert, H. (1936). J. Amer. med. Ass., Io6, I652.Elam, J. (1942). Lancet, 2, 309.Elkins, H. B. (I954). Arch. industr. Hyg., 9, 212.- (I96I). Arch. environm. Hlth, 2,45.

, Hobby, A. K., and Fuller, J. E. (1937). J. industr. Hyg.,19, 474.

- and Levine, L. (I939). J. industr. Hyg., 21, 221.Ellis, M. W., and Bryce Smith, R. (I965). Brit. med.J., 2, 14I2.

26o G. F. Smith


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Trichlorethylene: A Review

Enderby, G. E. H. (i94) Ibid., 2, 300.Extra Pharmacopoeia (I958). 24th Edition, the Pharma-

ceutical Press, London, p. 649.Fabre, R., and Truhaut, R. (I95I). Brit. J. industr. Med., 8,

275.and- (1952). Ibid., 9, 39.

Fahy, J. P. (I948). J. industr. Hyg., 30, 205.Fiessinger, N., and Laur, C. M. (I936). Presse mid., 44, 1797.

and Loeper, J. (194i). Arch. Mal. prof., 3, 296.Flinn, F. B. (1946). Amer. J. Med., 1, 388.Forssman, S., and Ahlmark, A. (1946). Nord. Med., 30, 1033.

, Gernandt, B., and Goldberg, L. (1948). Acta physiol.scand., I6, 256.

, and Holmquist, C. E. (i953). Acta pharmacol. (Kbh.),9, 235.

Foulger, J. H. (I949). J. Amer. med. Ass., 139, 826.Frant, R., and Westendorf, J. (1950). Arch. industr. Hyg., I,

308.Friberg, L., Kylin, B., and Nystrom, A. (I953). Acta

pharmacol. (Kbh.), 9, 303.Garland, Y. (I942). Brit. med. J3., 2, 607.G6nevois, L. (1936). Ann. Hyg. pubi. (Paris), 14, I39.Geiger, A. J. (1943). J. Amer. med. Ass., 123, I4I.Gerbis, H. (I936). Arch. Gewerbepath. Gewerbehyg., 7, 421.Giever, P. M., and Cook, W. A. (I960). Arch. environm. Hlth,

21, 233.Gisclard, J. B. (I960). Ibid., 21, 250.Glaser, M. A. (193I). J. Amer. med. Ass., 96, 9I6.Glynn, L. E., and Himsworth, H. P. (I948). Clin. Sci., 6,

235.Goldblatt, M. W., and Goldblatt, J. (1956). In Industrial

Medicine and Hygiene, vol. 3, Merewether, E. R. A.,p. 527. Butterworth, London.

Goldman, F. H., and Seegmiller, C. G. (I943). J. industr.Hyg., 25, I8I.

Gonin, A., and Fraisse, H. (I947). Arch. Mal. prof., 8, I75.Gordon, R. A., and Shackleton, R. P. W. (1943). Brit. med.

J., I, 380.Grandjean, E. (I960). Arch. environm. Hlth, I, Io6.

Munchinger, R., Turrian, V., Haas, P. A., Knoepfel,H. K., and Rosenmund, H. (I955). Brit. J7. industr.Med., 12, I31.

Griffiths, H. F. (I942). Lancet, I, 502.Gutch, C. F., Tomhave, W. G., and Stevens, S. C. (I965).

Ann. intern. Med., 63, I28.Guyotjeannin, M. C., and van Steenkiste, J. (1958). Arch.

Mal. prof., 19, 489.Habgood, S., and Powell, J. F. (I945). Brit. J3. industr. Med.,

2, 39.Hamilton, A., and Johnstone, R. T. (I945). Industrial

Toxicology, p. 639. Oxford Univ. Press, New York.Hargarten, J. J., Hetrick, G. H., and Fleming, A. J. (I96I).

Arch. environm. Hlth, 3, 46I.Harrold, G. C., and Gordon, L. E. (1939). . industr. Hyg.,

21, 491.Haworth, J., and Duff, A. (I943). Brit. med. 7., I, 38I.Helliwell, P. J., and Hutton, A. M. (I950). Anaesthesia, 5, 4.Herdman, K. N. (I945). Brit. med.J'., 2, 689.Herzberg, M. (I934). Anesth. Analg. Curr. Res., 13, 203.Hewer, C. L. (I942). Proc. roy. Soc. Med., 35, 463.

(I943). Ibid., 36, 463.and Belfrage, D. (1938). Lancet, 2, I290;and Hadfield, C. F. (I94I). Brit. med. J., I, 924.

Hickish, D. E., Smith, J. H., and Bedford, J. (I956). Brit.J. industr. Med., 13, 290.

Hildesheimer, S. (I92I). Dtsch. med. Wschr., 47, 748.Hill, C. A. St. (I966). Trans. Soc. occup. Med., i6, 6.Humphrey, J. H., and McClelland, M. (I944). Brit. med. J.,

I, 315.

Hunter, A. R. (I944). Lancet, I, 308.(I949). Brit. J3. Pharmacol., 4, I77.(I964). Neurosurgical Anaesthesia, p. 23. Blackwell,Oxford.

Hunter, D. (I944). Brit. med.J., 1, 341.(I957). The Diseases of Occupations, 2nd ed., p. 543.English Universities Press.

Imperial Chemical Industries. Non-Inflammable Solvents.Technical Booklet.

Isenschmid, R., and Kunz, E. (I93sa). Schweiz. med. Wschr.,I6, 530.

and -(Ig935b). Ibid., I6, 612.Jackson, D. E. (I934). Anesth. Analg. Curr. Res., 13, I98.James, W. R. L. (I963). Brit. J3. industr. Med., 20, 47.Joachimoglu, G. (192I). Berl. klin. Wschr., 58, 147.Johnson, E. E. (I945). Brit. med.JY., 2, 331.Johnstone, R. T. (I94I). Occupational Diseases, p. 452.

Saunders.Jones, G. W., and Scott, G. S. (1943). Anesthesiology, 4, 44I.Joron, G. E., Cameron, D. G., and Halpenny, G. W. (955).

Canad. med. Ass. J., 73, 890.Kay, K., Reece, G. M., and Drinker, P. (939). J. industr.

Hyg., 21, 264.Keenan, R. G. (I960). Arch. industr. Hlth, 21, 26I.Kitigawa, K. (I96I). Proc. I3th int. Congr. Occup. Hlth,

New York, I960, p. 506.Kleinfeld, M., and Tabershaw, I. R. (1954). Arch. industr.

Hyg., 10, I34.Kramer, F. (192I). Berl. klin. Wschr., 58, 149.Krantz, J. C., Carr, C. J., and Hame, W. G. (934). Proc.

Soc. exp. Biol. (N.Y.), 32, 334.-, -, Musser, R., and Hame, W. G. (I935). J. Pharma-

col. exp. Ther., 54, 327.Kulkarni, R. N. (I944). IndianJ. med. Res., 32, I89.Kylin, B., Reichard, H., Siimegi, I., and Yllner, S. (I962).

Nature (Lond.), 193, 395.Lachnit, V., and Pietschmann, H. (196I). Proc. 13th int.

Congr. occup. Hlth, New York, I960, p. 947.and Rankl, W. (1950). Z. Unfallmed. Berufskr., 43, 334.

Lancet (I944a). Annotation (i), I87.(I944b). Annotation (I), 379.(I944c). Annotation (I), 476.

Lande, P., Dervillee, P., and Nun, C. (I939). Arch. Mal. prof.,2, 454.

Levine, V. E., and Bien, G. E. (1934). Proc. Soc. exp. Biol.(N.Y.), 32, 335.

Lloyd Potter, A. (I958). Handbook of Industrial Hazards,p. I40. Imperial Chemical Industries.

Lloyd-Williams, K. G., and Hewspear, D. (I942). Brit. med.J., 2, I70.

Lob, M. (I960). Med. d. Lavoro, 5i, 587.Longley, E. O., and Jones, R. (I963). Arch. environm. Hlth,

7, 249-Love, W. S. (I937). Ann. intern. Med., Io, II87.MaLkinson, F. D. (I960). Arch. industr. Hlth., 2I, 87.Mallach, J. F., Marquardt, G. H., and Werch, S. C. (I943).

Amer. Hoart J., 26, 377.Maloof, C. C. (I949). J. industr. Hyg., 31, 295.Malten, K. E., and Zielhuis, R. L. (1964). Industrial Toxi-

cology and Dermatology in the Production and Processingof Plastics, p. 7I. Elsevier, Amsterdam.

Marquardt, G. H., Mallach, J. F., and Werch, S. C. (1943).Proc. Soc. exp. Biol (N.Y.), 52, 2.

Matruchot, D. (1944-I945). Arch. Mal. prof., 6, 396.McAuley, J. (I943). Brit. med. J., 2, 713.McBirney, R. S. (1954). Arch. industr. Hyg., I0, 130.McCollum, J. L. (1930). J. Pharmacol. exp. Ther., 40, 305.McCord, C. P. (1932). J. Amer. med. Ass., 99, 409.McLaughlin, R. R. M. (1936). Ibid., Io6, I605.

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ctober 1966. Dow

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Merewether, E. R. A. (I956). Industrial Medicine andHygiene, vol. 3. Butterworth, London.

Mikiskova, H., and Mikiska, A. (I960). Arch. Gewerbepath.Gewerbehyg., I8, 3I0.

and - (I966). Brit. J. industr. Med., 23, i i6.Ministry of Labour. Methods for the Detection of Toxic

Substances in Air. Booklet 8. H.M.S.O., London.Methods for the Detection of Toxic Substances in Air.Booklet 12. H.M.S.O., London.Safety, Health and Welfare No. 8. H.M.S.O., London.Safety, Health and Welfare No. i5. H.M.S.O., London.

Ministry of National Health and Welfare, Canada (I949).Guide to the Diagnosis of Occupational Diseases. King'sPrinter, Canada.

Morgan, D. J. (I964). Ann. occup. Hyg., 7, 365.- and Duxbury, G. (I965). Ibid., 8, 253.Morrison, J. L. (1946). J. Pharmacol. exp. Ther., 86, 336.Morton, H. J. V. (I943). Brit. med. J., 2, 828.Naish, N. (I945). Ibid., 2, 367.O'Connor, W. A. (1954). Ibid., 2, 451.Oettingen, W. F. von. (I937). J. industr. Hyg., 19, 349.

(I964). The Halogenated Hydrocarbons of Industrial andToxicological Importance, p. 240. Elsevier, Amsterdam.

Oljenick, I. (1927). Ned. T. Geneesk., I, 812.- (1928). J. Amer. med. Ass., 9I, I085.Ollivier, H. (I944-1945). Arch. Mal. prof., 6, 159.Ostlere, G. (1948). Brit. med. J., I, i95.Pask, E. A. (I942). Proc. roy. Soc. Med., 35, 545.Patoir, A., Marchand, M., and Ducarne, F. (I943). Arch.

Mal. prof., 5, I64.Patty, F. A. (I939). J. industr. Hyg., 21, 469.Paykoc, Z. V., and Powell, J. F. (I945). J. Pharmacol. exp.

Ther., 85, 289.Pernell, C. (I944). J. industr. Hyg., 26, 33I.Plessner, W. (i9I6a). Berl. klin Wschr., 53, 25.- (I9I6b). Ibid., 53, 514.

Powell, J. F. (1945a). Brit. J. industr. Med., 2, 142.(1945b). Ibid., 2, 212.

-947). Ibid., 4, 233.Priest, R. J., and Horn, R. C. (x965). Arch. environm. Hlth,

II, 36I.Prosser White, R. (I934). The Dermatergoses or Occupational

Affections of the Skin, 4th ed., p. 220. Lewis, London.Riegel, E. R. (I949). Industrial Chemistry. Reinhold, London.Rivoire, J., Genevois, M., and Tolot, F. (I962). Arch. Mal.

prof., 23, 395-Roche, L., Genevois, M., and Marin, A. (I958). Ibid., I9,

6i5.Rogers, G. W., and Kay, K. K. (I947). J. industr. Hyg., 29,

229.Ross, J. H. (I923).,J. biol. Chem., 58, 641.

Rubinstein, H. S. (1937). Arch. Neurol. Psychiat. (Chic.), 37,638.

-, Painter, E., and Harne, 0. G. (I939). J. Lab. clin. Med.,24, 1238.

Schwartz, L., and Russell, J. P. (I94I). Pub. Hlth Rep.(Wash.), 56, i58i.

, Tulipan, L., and Birmingham, D. J. (1957). Occupa-tional Diseases of the Skin, 3rd ed. Lea and Febiger,Philadelphia.

Seelert (1922). Klin. Wschr., I, 2228.Seifter, J. (iX944). J. industr. Hyg., 26, 250.Silverman, L. (i943). Ibid., 25, 306.- , Reece, G. M., and Drinker, P. (I939). Ibid., 21, 270.Soucek, B., and Vlachova, D. (ig60). Brit. Jr. industr. Med.,

17, 60.Spain, D. M. (i965). Arch. environm. Hlth, II, 364.Spolyar, L. W., Harger, R. N., Keppler, J. F., and Bumsted,

H. E. (i95i). Arch. industr. Hyg., 4, i56.Stentiford, H. B., and Logan, C. J. H. (1956). Lancet, 2, 659.Stephens, J. A. (I945). Brit. med.3J., 2, 2i8.Striker, C., Goldblatt, S., Warm, I. S., and Jackson, D. E.

(i935). Anesth. Analg. Curr. Res., 14, 68.Stuber, K. (193I). Arch. Gewerbepath. Gewerbehyg., 2, 398.Talvitie, N. A. (i958). Arch. industr. Hlth, 17, 563.Tara, S. (1944-I945). Arch. Mal. prof., 6, 319.Taylor, H. (1936). J. industr. Hyg., i8, I75.Teare, D. (0948). Brit. med. J., 2, 559.Tebbens, B. D. (i937). J. industr. Hyg., 19, 204.Teisinger, J. (i96i). Proc. 13th int. Congr. occup. Hlth,

New York, ig60, p. 987.Todd, J. (1954). Brit. med. J'., I, 439.Trense, E. (i965). Zbl. Arbeitsmed., xS, II4.Trott, D. G. (i966). Personal Communication.Trumper, H. B., Thelwall Jones, A., and Taylor, H. (1936).

Lancet, 2, 1390.Tubich, G. E., Davis, I. H., and Bloomfield, B. D. (ig60).

Arch. industr. Hlth, 21, 424.Wagner, F. W. E. (1946). IrishJ3. med. Sci., 6th ser., p. 7I7.Waters, R. M., Orth, 0. S., and Gillespie, N. A. (i943).

Anesthesiology, 4, I.Webb, F. J., Kay, K. K., and Nichol, W. E. (1945). J.

industr. Hyg., 27, 249.Weitbrecht, U. (i965). Zbl. Arbeitsmed., IS, I38.Willcox, W. (I934a). Proc. roy. Soc. Med., 27, 455.- (1934b). Brit. med.JI., I, 105.

Wirtschafter, Z. T., and Cronyn, M. W. (i964). Arch.environm. Hlth, 9, I8o.

Witheridge, W. N., and Walworth, H. T. (1940). J. industr.Hyg., 22, I75.

Woodard, G., Lange, S. W., Nelson, K. W., and Calvery,H. 0. (1941). Ibid., 23, 78.

Wurm, E. (193I). Arch. Gewerbepath. Gewerbehyg., 2, 767.

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