Allergic contact to ultraviolet - Research on the …oem.bmj.com/content/oemed/40/3/241.full.pdf · cost of raw materials and health ... epicutaneous tests were in association with

British Journal of Industrial Medicine 1983;40:241-250

Allergic contact dermatitis due to urethane acrylate inultraviolet cured inksJ R NETHERCOTT, H R JAKUBOVIC, C PILGER, AND J W SMITH

From the Department of Occupational and Environmental Health, St Michael's Hospital, University ofToronto, Toronto, Ontario, Canada

ABSTRACI Seven workers exposed to ultraviolet printing inks developed contact dermatitis. Sixcases were allergic and one irritant. A urethane acrylate resin accounted for five cases of sensitisa-tion, one of which was also sensitive to pentaerythritol triacrylate and another also to an epoxyacrylate resin. One instance of allergy to trimethylpropane triacrylate accounted for the sixth caseof contact dermatitis in this group of workers. An irritant reaction is presumed to account for thedermatitis in the individual not proved to have cutaneous allergy by patch tests. In this instancetrimethylpropane triacrylate was thought to be the most likely irritating agent. Laboratory inves-tigation proved urethane acrylate to be an allergen. The results of investigations of the sensitisa-tion potentials of urethane acrylate, methylmethacrylate, epoxy acrylate resins, toluene-2,4-diisocyanate, and other multifunctional acrylic monomers in the albino guinea pig are presented.The interpretation of such predictive tests is discussed.

Inks and coatings based on acrylated resins, reactivelow molecular weight acrylates, and light absorbingchemicals have established specific uses in industryin the last decade.' These materials have not becotfneas widely used as was originally expected2 due to thecost of raw materials and health problems, princi-pally cutaneous disease, that have arisen in workersmanufacturing them3-5 and using the finished pro-ducts containing them.6-8

Binding of acrylated oligomer such as acrylatedalkyds, acrylated epoxy resins (EAs), polyester acry-lates, or acrylated vegetible oils such as acrylatedlinseed oil) (fig 1) to dry the ink is accomplished by ahighly reactive acrylate with more than one acrylatefunctional group, known as a multifunctional acrylicmonomer (MFAs), which acts as a cross linkingagent chemically reacting with two or more adjacentoligomers to bind them together. These MFAs,which are more highly reactive than the more wellknown monomeric acrylic monomers-for instance,methyl methacrylate (MMA)-include: pentaery-thritol triacrylate (PETA), trimethyl propane triac-rylate (TMPTA), and hexanediol diacrylate(HDODA) (fig 2). Low molecular weight EAs andurethane acrylate resins (UA) are now being used ascross linking agents replacing MFAs (fig 3). A

Received 6 January 1982Accepted 26 August 1982

chromophore such as an aromatic ketone, benzoin,or a chlorinated aromatic compound which absorbsphotons of ultraviolet light (emitted from a fluores-cent tube with a continuous emission of light of300-400 nm wave length), transfers the energyabsorbed to the cross linking acrylic chemical byhomolytic fragmentation of the photoinitiator orexcitation of the photoinitiator to a triplet state withelectron transfer to the cross linking chemical. Theactivated acrylate thus formed then binds to theacrylated ends of the polymer effecting cure,2 whichresults in virtually instantaneous drying of the ink orcoating. As the low molecular weight acrylate is oflow viscosity, it may often be used as a diluent forthe other system components rather than a hyd-rocarbon solvent, as has been the case in conven-tional inks and coatings. This offers the advantagethat almost no loss of coating thickness occurs withdrying as the diluent is bound up in the final cured ordried material rather than evaporating as in conven-tional systems. This feature has great usefulness incertain applications-for instance, in coating sys-tems to prevent dental caries where the dental coat-ing applied in this fashion dries without leaving anybreaks that might allow passage of bacteria into thecoated tooth.3

Allergic contact dermatitis due -to the acrylatecross linkers PETA, TMPTA, and HDODA havebeen reported. 45 Sensitisation to EA resin has alsobeen documented.457-9 EAs and PETA have been

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Nethercott, Jakubovic, Pilger, and Smith

Acrylated polyester

0 0 011 11 if

CH2=CH-C-(OCH2CH2 )3-O-C-(CH2 )4-C-0-CH2-0 011 11

-0U C-O -CH2-CH-0-C-CH=CH2

Acryloted alkyd

CH3 CH30 CH2 0 0 OH2 0o1 o 11 Fig 1 Acrylated oligomers

CH2=CH-C-O-0H2-O-OH200-(CH2)4 -C-0-CH2-C--OH2-0-C-CH=CH2 commonly in use commercially.CH2 CH2

O 0

C-CH=CH2 0=CO CH=0H2

Acryloted epoxy

0 OH CH3 OH 0C1 =I

CH2 CH000H-U2 0H0CH2O uutr002 -0-OH2-0-O-C0H=CH2

Pentoerythritol triocrylote (PETA)

O CH20H 0

11 11CH2=CH- C-O-OH2 -C-CH2 -O-C-CH=CH2

IIUH2-0-IC-CH=CH20

Trimethylolopropone triocrylote (TMPTA)

CH3

O CH2 0

CH2 =CH-C-OCH2 -C-CH2 -0-O-CH=CH2

OH2 -OC-CH= CH2

0

Hexonediol diacrylote (HDODA)

0 0

11 11CH2 =CH-CO-CH2 -CH2 -CH2 -CH2 -CH2 -CH2 -0-C-CH=CH2

Fig 2 Some multifunctional acrylic chemicals in use as

cross linking agents in ultraviolet curing systems.

shown to possess cutaneous sensitisation potential inthe guinea pig.7 10Our purpose is to report a group of workers hand-

ling ultraviolet sensitive printing inks whodeveloped cutaneous allergy to UA in the inks andto present experimental evidence regarding the rela-tive allergenic potential of urethane acrylate com-pared with other sensitisers using a guinea pigmodel.

Printing process

All affected workers were employed in a plant thatmanufactured plastic food containers. The contain-ers had print applied to their exterior by way of anoffset printing process. The plastic containers werefed to the printing plates on an apparatus resemblinga "ferris wheel" (fig 4). The container was rotatedagainst the printing plates as it went around and wasthen discharged on to a conveyor belt that took theprinted container past a bank of intense ultravioletlamps to dry the printed surface (fig 5). The workerswere principally exposed to the inks when theyrefilled reservoirs (fig 6) and when using solvents toclean up the press between press runs. Gloves werenot routinely worn during either of these proce-dures. Occasionally workers had to mix inks to pro-duce a particular colour, and under certain condi-

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Allergic contact dermatitis due to urethane acrylate in ultraviolet cured inks

CH3

CH2 =CH-C-NJ N-8CH H

R Polyol group

H H

OH3

-0-R-0-C-N H NH2H

Fig 3 Structure ofurethaneacrylate resins.

Fig 4 Interstices ofoffset press used to print on containers.Containers move on arms ofwheel to engage printing plates,then spin around on end ofarm through a 3600 arch toallow application ofprint to entire outside surface ofcontainer.

Fig 5 Conveyor belt carrying freshly printed containersinto tunnel lined with intense ultraviolet light emittingfluorescent tubes to dry ink. Note exhaust to remove ozoneand nitrous oxide.

Fig 6 Reservoirs for ink that have to be filed by hand.

tions it was also necessary to add TMPTA to a givenink to reduce the ink viscosity to facilitate betterdispersion of the ink on the printed surface or toenhance the cure rate to allow adequate drying.During both the formulation of the specific ink col-ours and the dilution of inks with TMPTA there wasa serious risk of skin contamination with theultraviolet curing system components.

CLINICAL FEATURESEight press operators and two foremen worked inthis plant; seven experienced cutaneous problemsvarying from severe eczematous dermatitis of thedorsal hands, forearms, arms, neck, and eyelids(case 1) to erythematous scaling in distinct evanes-cent patches on the dorsal hands (case 7) (table 1).

CLINICAL INVESTIGATION

Materials and methodsThe chemicals outlined in table 2 were used forpatch tests. AU chemicals used had been shown to benon-irritant in the concentration and vehicle testedin 20 normal human subjects. The materials wereapplied to "Al-test strips" (Hollister-Stier Ltd) thatwere then fixed to the upper back of each subject

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Table 1 Findings in workers with cutaneous complaints

Case Sex Job description Symptoms and signs Clinical diagnosis

1 F Machine operator Itchy red patches on face, neck, forearms, Allergic contact dermatitisand hands when working with inks

2 M Foreman in printing department Itchy red patches on face, ears, wrists Allergic contact dermatitiswhen working with inks

3 M Foreman in printing department Itchy red patches on penorbital skin and Allergic contact dermatitisforearms when workin with inks

4 F Mixing inks, machine operator Itchy red patches on nen, forearms, Allergic contact dermatitishands when working with inks

5 F Machine operator Itchy red patches on periorbital skin, Allergic contact dermatitisforearms, hands, when working with inks

6 F Machine operator Itchy, buring red swollen patches under Allergic contact dermatitiseyes when workng with mks

7 F Machine operator Erythematous, slightly pruritic patch on Irritant contact dermatitisarms

Table 2 Results ofepicutaneous tests in seven workers patch tested

Chemicals Case I Case 2 Case 3 Case 4 Case S Case 648h 96h 48h 96h 48h 96h 48h 96h 48h 96h 48h 96h

Urethane acrylate 01% in 3+ 3+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ - -petrolatum

Pentaerythritol triacrylate 3+ 3+ - - - - - - - - - -0 1% in petrolatum

Trimethylpropane triacrylate - - - - - - - - - - 2+ 2+0-1% in petrolatum

Hexanediol diacrylate - - - -

0 1% in petrolatumEpoxy acrylate resin I - - 1+ 1+1% in petrolatum

Epoxy acrylate resin2 - - --21% in petrolatum



Methylmethacrylate - - - -

1% in petrolatumToluene 2, 4 diisocyanate - - - - - - - - - - - -

0-1% in acetone

0 = No reaction.1 + = Macular erythema.2+ = Oedematous or vesicular reaction.3+ = Spreading, bullous, or ulcerative reaction.

with Dermicel tape (Johnson & Johnson Ltd) asrecommended by the North American ContactDermatitis Group."

Patches were removed at 48 hours. The sites wereexamined and scored after the pressure effect of the"Al-test strip" had resolved-that is, after about 30minutes. The scoring system recommended byInternational Contact Dermatitis Group'2 was usedas noted in table 2. The sites were examined furtherat 72 and 96 hours.

In case 1 a 2 mm punch biopsy of the skin wastaken from the centre of the urethane acrylate patchtest site shortly after the 48 hour visual scoring pro-cedure. The skin biopsy specimen was fixed in for-malin and processed for light microscopic examina-tion using haematoxylin-phloxine-saffron staining.

RESULTSTable 2 outlines the patch test results. No positivereactions were elicited to EA resin 2, EA resin 3,EA resin 4, toluene-2,4-diisocyanate (TDI),HDODA, or MMA. Five of the seven workerstested (cases 1-5) showed positive patch test resultsto UA. Figure 7 illustrates a 48 hour patch test reac-tion to UA 0*1% in petrolatum in case 1; thispatient also manifested a simultaneous autosensit-isation dermatitis of her forearms at the time of thepositive patch test. Single instances of sensitivity toPETA, TMPTA, and EA resin 1 occurred. TMPTAwas the sole sensitiser in one case (case 6) while inthe case of PETA and EA resin 1 the positiveepicutaneous tests were in association with a posi-tive response to urethane acrylate.

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cm 2 3 4Fig 7 Site ofcutaneous reaction to a patch test withurethane acrylate 0*1 % in petrolatum at 48 hours in case 1.

The skin biopsy specimen in case 1 taken from theUA patch test reaction site at 48 hours showedepidermal spongiosis, dermal oedema, and asuperficial perivascular lymphocytic infiltrate withexocytosis (fig 8) consistent with allergic contactdermatitis.'3

LABORATORY INVESTIGATION

Sensitisation potentalAnimals-Albino Hartley/Dalkin strain female

guinea pigs weighing 300-500 g were obtained from

Vb-~9* ,; *sx j Fig 8 Biopsy speciak Wtcase I at 48 hours. I* < * ,;^ >44 % wlymphocytic perivas,

* t' ~ Haematoxylin-phlow

'I ..@S*..''w...4,x *J t. At

the Connaught Laboratories, Toronto, Canada.They were housed in metal cages and fed PurinaGuinea-Pig Chow and fresh water freely.

Irritancy testingVarious strengths of UA, TMPTA, HDODA,PETA, MMA, and tripropylene glycol diacrylate(TPGDA) in propylene glycol, all of which werefully dissolved or fully agitated if not entirely misc-ible, were intradermally injected into groups of 10control guinea pigs. The animals were examined 24hours after injection to determine the maximumconcentration that did not cause severe injury orsystemic toxicity. This concentration was used as thehighest concentration in the subsequent sensitisationinduction procedure.Other groups of 10 control guinea pigs were topi-

cally exposed to the seven chemicals at various con-centrations in petrolatum. Three concentrations ofeach chemical were applied to "Al-test strips" thatwere affixed to the animals' shaved flanks by occlu-sive tape (Blenderm, 3M Company) that was thencovered by a three inch (7.6 cm) elastic adhesivebandage (Elastoplast, Smith and Nephew Co) wrap-ped firmly around their torsos. The bandages wereremoved after 24 hours and the sites were examinedat 48 hours for evidence of reaction. The non-irritant concentration ascertained by this methodwas used to patch test the animals after the sensitisa-tion procedure to determine whether they hadbecome hypersensitive.

Sensitisation procedureThe method described by Magnusson and Kligman'4was used but with multiple intradermal induction

imen of the positive patch test inNote epidermal spongiosis andrcular infiltrate.xine-saffron strain (400 x).

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Table 3 Percentage ofanimals sensitised, comparative sensitisation values, and various induction and challengeparameters for acrylic monomers, toluene diisocyanate, and urethane acrylate

Chemical Intradermal No of No % Sensitised Intradermal sensitisinginduction animals sensitised by probit concentration for 50% of theconcentration calculatons animals (IDSC,d in %

PETA 0-001 5 2 15-40-01 15 8 55-6 0-0050-05 5 4 93*30.5 10 10 100

TDI 2-5 10 5 NC 2*5TMPTA 0-5 10 4 20 5.4

10-0 20 10 58-3HDODA 0-83 10 1 3-9

2-5 10 3 20 4-35-0 10 5 507-5 10 6 79-0

TPGDA 1-0 10 3 12-52-5 10 4 33.3 3.55-0 10 5 60-08-5 6 3 83-3

MMA 5 5 0 010 5 2 22-2 14-815 5 2 50-025 5 4 88-9

UA 7-5 10 7 63-615-0 10 9 94-1 5.7*39 10 10 100

*Extrapolated value.NC = No probit calculation performed.PETA = Pentaerythritol triacrylate.TDI = Toluene-2,4-diisocyanate.TMPTA = Trimethyl propane triacrylate.

HDODA = Hexanediol diacrylate.TPGDA = Tripropylene glycol diacrylate.MMA = Methyl methacrylate.UA = Urethane acrylate.

concentrations administered. Table 3 notes thenumber of animals used at each intradermal con-centration. Induction was performed in two stages.In the first stage either side of the shoulder regionwas injected intradermally. Three pairs of intrader-mal injections of the following composition weremade into each group of animals:

(1) 0 1 ml of the respective chemical in propyleneglycol in the concentration noted in table 3.

(2) 0-05 ml of Freund's adjuvant (Freund's com-plete adjuvant, Difco Laboratories, Detroit,Michigan) mixed with 0O05 ml of the chemical inpropylene glycol injected as in (1).

(3) 0O1 ml of Freund's complete adjuvant.One week after injection the shoulder region of eachanimal was clipped. The six chemicals were appliedin their respective concentrations in petrolatum, asnoted in table 3, on a 2 cm x 4 cm 3MM Whatmanfilter paper that was applied over the sites of previ-ous intradermal injection. The filter paper was heldin place by impervious plastic tape (Blenderm, 3MCompany) covered with a three-inch (7.6 cm) elasticadhesive bandage wrapped firmly about the animals.The bandages were removed 48 hours after theywere applied.

Challenge testingAll animals were challenged two weeks after topical

exposure. A 5 cm x 5 cm area of the flank wasclipped and then shaved with care to avoid abradingthe skin. The challenge concentrations were non-irritant concentrations that had been determined incontrol animals as described above. The patcheswere applied as described above to assess irritancy.After 24 hours the patches were removed. The siteswere examined at 48 hours for evidence of reaction;no endeavour was made to score the intensity of thereaction.

RESULTSTable 3 notes the proportion of animals exhibitingreactions. Probit analysis was carried out using log-probability paper to calculate the intradermal (ID)concentration required to sensitise half the guinea-pigs (IDSC50), except for TDI, which was tested atonly one concentration.'5 The sensitisation potentialof each of the chemicals was compared with that ofPETA and MMA as noted in table 3.

IRRITANCY POTENTIALAnimalsSix New Zealand white female adult rabbits weigh-ing about 500 g, obtained from the Guelph Rab-bitry, Guelph, Ontario, were housed individually inmetal cages and fed Purina Rabbit Chow and freshwater freely.

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MethodThe method described by Draize and associates'6was used. After shaving the lower back of the rab-bits, 0-5 ml of 100% urethane acrylate was appliedto the skin to an abraded and non-abraded site of2 cm x 2 cm. The two sites were occluded withsterile 2 cm x 2 cm gauze squares that were in turnheld in place with an elastic adhesive bandage. Theocclusive bandages and gauze were removed after24 hours, and the sites were examined at 48 hoursafter application for evidence of cutaneous reaction.Reactions were scored using the standard method.'6

ResultsThe cutaneous irritancy score determined by thisexperiment was 0-75/8.

INFRARED AND HIGH PRESSURE LIQUIDCHROMATOGRAPHY INVESTIGATION OFURETHANE ACRYLATETechnical grade urethane acrylate supplied to us bythe manufacturer of the printing ink was analysed byinfrared spectroscopy. No absorbance was detectedin the 2260 cm-' region where the isocyanate groupabsorbance should be found. A sample was mixedwith toluene-2,4-diisocyante to give a concentrationof 0-606% TDI w/w. This "doped" sample yielded areadily detectable absorbance at 2260 cm-' due tothe added diisocyanate. It was accordingly con-cluded that the urethane acrylate as supplied con-tained less than 0-6% free isocyanate. Samples ofUA, PETA, TMPTA, and HDODA were analysedby a reverse phase high pressure liquid chromato-graph equipped with a 254 nm fixed wavelengthdetector and a 30 cm octadecylsilane column. Theinstrument was operated in programmed gradientelution mode with a water/acetonitrile solvent sys-tem. Flow rate was 0-8 mlVminute with a gradientrunning from 30% acetonitrile to 100% in 10minutes. Total analysis time was 14 minutes.The urethane acrylate chromatogram consisted of

two major peaks that could not be completely resol-ved and four minor peaks, which together rep-resented 9% of the total peak area.Chromatography of TMPTA and HDODA under

the same instrument conditions yielded a single peakfor each. Retention times did not match the reten-tion times of any of the components in the urethaneacrylate sample.The PETA sample, when chromatographed under

the same conditions, yielded six peaks, none ofwhich had retention times matching those of theurethane acrylate components. The five minor peaksin the PETA chromatogram were assumed to rep-resent hydrolysis products of PETA, present asimpurities. One of these was identified as acrylic

acid by comparison with a chromatogram of anauthentic sample of the acid. The other componentswere not investigated further. No peak was detectedin the urethane acrylate chromatogram with thesame retention time as acrylic acid.Based on the HPLC data, it was concluded that

the urethane acrylate as supplied contained noPETA, TMPTA, HDODA, or free acrylic acid.

Comment

The cutaneous disease of the seven affected workerswas characteristic of contact dermatitis, based on thedistribution and character of the lesions and the timecourse of the eruptions, all of which support thediagnosis. Historical data elicited from the workersconfirmed a relation to work.

It is well recognised that the light sensitive inks towhich these workers were exposed possess compo-nents with both irritant and allergic properties.' 3-8Initial investigation in case 1 suggested that PETAwas the culprit, but when it was discpvered that itwas not in the ink formulations in use at that time inthe plant further investigation was undertaken. Thisled to the discovery of positive epicutaneous tests tourethane acrylate in case 1 and five other workers.Individuals sensitive to TMPTA and EA 1 resin inaddition to urethane acrylate were also found.TMPTA allergy was not surprising as it had beenreported previously.' 23Having identified urethane acrylate as the causal

agent, chemical analysis was carried out to ascertainwhether TDI, acrylic acid, or some other contamin-ant from the chemical synthesis present in the com-mercial material might be the true allergen, ratherthan urethane acrylate. No detectable isocyanatewas found; this, combined with the negative patchtest response to TDI, excluded it as the cause.Unreacted acrylic acid could not be detected either,ruling it out as the cause. Accordingly, it was con-cluded that urethane acrylate was the source of theallergic contact dermatitis in the five workers withpositive patch test reactions to urethane acrylate.Two instances of positive epicutaneous tests to

other acrylated chemicals were found in associationwith sensitivity to urethane acrylate. As cross reac-tivity between acrylates is uncommon,' ' the chemi-cal structures differ, and, in the instance of PETA,no contamination of urethane acrylate with it or anunreacted chemical was shown by chemical analysis,it is reasonable to conclude that as the individualshad been exposed to all three chemicals, the multi-ple causal reactions represent concurrent sensitisa-tion rather than cross reactions. It is once againimportant to note, as has been noted in the past, thatthere was no cross reactivity shown between any of

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the acrylated chemicals and MMA, which has in thepast been commonly used as a screening test foracrylate sensitivity.

Case 7 seems to have recurrent irritant contactdermatitis probably secondary to TMPTA, which isa moderately irritating material'8 found in the inks.The irritancy of urethane acrylate determined by theDraize method in this report excludes it as the causeof irritation in case 7.19 EA resins, which also havelow Draize scores, were excluded as likely causes onthe same grounds.

Laboratory investigation of the sensitisationpotential of urethane acrylate has confirmed itsallergenicity. In table 3 the potential of MFAs usedin these photo-cured materials as well as MMA andTDI are presented to allow a comparison ofurethane acrylate with other chemicals with longerusage experience. Table 4 gives the results of pastexperiments with EA resins found in the samecommercial products with their respective IDSC,Ovalues. PETA has a very low IDSC50 value relativeto all of the other chemicals investigated; MMA hasa relative high value. Thus the former chemicalPETA seems to possess a high potential to inducecutaneous allergy, at least in the guinea pig, whilethe latter has a relatively low propensity to do so.These relative differences may overestimate the sen-sitisation potential of EA resins somewhat as thetopical induction concentrations used in the EAresin experiments were higher than the concentra-tion chosen for the chemicals in table 3. Given this,these chemicals are probably either more or lesspotent allergens than MMA and PETA respectively,based on their IDSC30 values.The IDSCSO value for urethane acrylate has been

extrapolated, and this value and that for EA 1,

EA 2, and EA (b) are thus not as accurate as theother values presented. Given this, urethane acrylateis likely to exhibit a sensitisation potential similar toTMPTA and less than the other MFAs, especiallyPETA. It may be a more potent allergen thanMMA.The usage experience presented in this report

shows urethane acrylate to be a more potentallergen than TMPTA despite the experimental datafrom the animal investigation suggesting that thetwo chemicals possess similar allergenicity in theguinea pig.How urethane acrylate relates to PETA in terms

of the practical risk of causing skin allergy duringuse based on this group of workers is uncertain as

exposure to PETA in this particular group is notknown because the period of exposure to PETA inthe ink formulations used was not ascertainablefrom the ink manufacturer. Previous usage experi-ence with PETAI4 led to many ink formulationworkers becoming allergic to it, much like the pres-ent instance with urethane acrylate in this group ofworkers. Whether PETA is a more or less potentallergen than urethane acrylate during use cannot beanswered now as the conditions of exposure in thisprevious group of workers was not comparable withthose reported herein. The previous workers wereexposed to PETA as a raw material in an ink man-ufacturing process, whereas the present group hand-led urethane acrylate only as a component infinished ink products.Urethane acrylate may be a less potent allergen

than TDI based on these findings in the guinea-pig,despite the fact that isocyanate monomers are wellknown but infrequently documented skinallergens.'2 20-22

Table 4 Percentage ofanimals sensitised, comparative sensitisation values, and various induction and challengeparameters for urethane acrylate resins

Chemical Intradermal No of No % Sensitised Intradermal sensitisinginduction animals sensidsed by probit concentration for SO% of theconcentraton calculations animals (IDSC5d in %

EA 1* 1 10 7 63-6 0-73 10 9 94-1

EA 2* 1 10 7 63-6 0-73 10 9 94-1

EA 3t 1 10 5 33-315 10 6 68.8 3-445 10 9 95-2

EA 4t 45 10 4 NC 45EA (b)t 1 10 7 53-9

3 10 7 82.4 5-5t10 10 10 100

Topical induction concentration was 50%.tTopical induction concentration was 100%.*Extrapolated value.NC = No probit calculation performed.

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These experiments have shown the well recog-nised monomeric acrylate allergen' to be a lesspotent allergen than the MFAs, urethane acrylate,EA resins, and TDI as illustrated by its IDSC50 rela-tive to those of the other chemicals as noted in tables3 and 4. The relatively low sensitisation potential ofMMA is reflected in the low incidence of cutaneoussensitisation reported to it' compared with the inci-dence of sensitisation to urethane acrylate in thisgroup of workers.Though urethane acrylate and TMPTA possessed

equivalent allergenicity in the animal experiments,the lower apparent practical risk of sensitisation toTMPTA reflected in the relative incidence ofcutaneous allergy to these two chemicals in thisspecific group of workers illustrates that animalstudies, especially when one injects the chemicalinto the skin as in these experiments, may not cor-rectly predict the practical risk of sensitisation inman or "predict the likelihood of sensitisation" inman-that is, risk.The explanation for this disparity between the

experimental and human experience with urethaneacrylate and TMPTA may rest, in part, on the lowirritancy of urethane acrylate, which has a Draizescore of 075/8 compared with TMPTA which has ascore of 5-2/8.'7 This relative lack of irritancy ofurethane acrylate has probably resulted in greaterskin contact as the inks containing it would not irri-tate the skin, and workers would be inclined to leavethe ink on the skin for longer periods, thus increas-ing the chance of sensitisation. This hypothesis doesnot fully explain the difference, though. EA resins,such as EA 1, EA 2, and EA (b) have IDSC5O valuesmuch lower than urethane acrylate and lower irri-tancy based on their Draize scores. Despite this,they do not appear to sensitise appreciable numbersof those exposed to inks containing them.6 Theexplanation may rest in solubility differences thatmay affect cutaneous penetration, in turn alteringthe chance of penetration of the chemical into theskin and the chance of inducing allergy. The intra-dermal method of induction in the animal experi-ments circumvents this. In keeping with this, solubil-ity differences definitely exist between EA resinsand urethane acrylate wherein the former chemicalsare not well solubilised in propylene glycol while thelatter, as well as MFAs and MMA, are quite soluble.Animal investigation can shed light on the relative

ability of cutaneous contactants to induce allergy.Such information is useful when endeavouring toreduce the hazard of the use of chemicals known tosensitise. In such instances it may not be possible touse a material that is absolutely safe-that is, non-sensitising-but only relatively safe. Comparison ofthe sensitisation potential of potent allergens, taking

intradermal induction concentration into considera-tion as illustrated in these experiments, may allow amore discriminating method of comparison or rela-tive allergenicity than is provided by the standardgrading system originally proposed by Magnussonand Kligman.'4The problem illustrated in this clinical situation

with respect to such predictive laboratory tests isthat the model considers relative sensitisation poten-tial only within the confines of clearly defined, artifi-cial conditions. Extrapolation to working conditionsmay have to take other factors into consideration, ofwhich penetration through intact skin and likelyexposure time in use are two. It is clear from thedifferences evident between the animal experimentsand working circumstances with TMPTA, EA, andurethane acrylate that such predictions are complex.Urethane acrylate resin is a cutaneous allergen

that ranks comparably with PETA in its ability tocause allergic contact dermatitis when used in print-ing inks. The substitution of urethane acrylate forPETA offers no great health advantage. Both chem-icals are relatively more hazardous than TMPTA,HDODA, or EA resin in this particular use.

References

'Nethercott J. Skin problems associated with multifunctionalacrylic monomers in ultraviolet curing inks. Br J Dermatol1978;95:541-52.

2 Rybny C, DeFazio C, Shahidi I, et al. Ultraviolet radiation curedcoatings. Journal of Paint Technology 1974;46:60-9.

3 Rock W. Fissure sealants-results of a three year clinical trialusing ultraviolet sensitive resin. Br Dent J 1977:142:16-8.

4 Emmett E, Kominsky J. Health hazard evaluation. Cincinnati,Ohio: United States Department of Health, Education andWelfare, National Institute for Occupational Safety andHealth, 1975. (Report No 75-106-247.)

Emmett E, Kominsky J. Allergic contact dermatitis fromultraviolet cured inks. JOM 1977;19:113-5.

6 Emmett E. Contact dermatitis from polyfunctional acrylicmonomers. Contact Dermattis 1977;3:245-8.

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