34 Plastic Materials

Contents

Introduction . . . . 584

34.1 Acrylic Resins . . . . 584

Bert Björkner 34.1.1 Monoacrylates and Monomethacrylates . . . 584

34.1.2 Multifunctional Acrylates . . . . 586

34.1.3 Prepolymers . . . . 588

34.1.4 Epoxy Acrylates . . . . 588

34.1.5 Urethane Acrylates . . . . 588

34.1.6 Polyester Acrylates . . . . 588

34.1.7 The Effects of Acrylate Esters on the Skin . . 590 34.1.8 Acrylonitrile . . . . 592

34.1.9 Skin Problems from Acrylonitrile . . . . 592

34.1.10 Acrylamide and Derivatives . . . . 592

34.1.11 Health Effects from Acrylamide and Derivatives . . . . 592

34.1.12 Cyanoacrylates . . . . 593

34.1.13 Care in the Handling of Acrylic Resins . . . . 593

34.1.14 Patch Testing with Acrylic Compounds . . . 594

34.2 Epoxy Resin Systems . . . . 595

Ann Pontén 34.2.1 Epoxy Resins . . . . 595

34.2.2 Hardeners . . . . 596

34.2.3 Epoxy-Reactive Diluents . . . . 597

34.2.4 Skin Hazards from Epoxy Resin Systems . . 597 34.2.5 Patch Testing with Epoxy Resin Systems . . . 598

34.2.6 Preventive Measures when Handling Epoxy Resin Systems . . . . 599

Suggested Reading . . . . 599

34.3 Phenol-Formaldehyde Resins . . . . 600

Erik Zimerson 34.3.1 Skin Hazards from Phenol-Formaldehyde Resins . . . . 601

34.3.2 Patch Testing with Phenol-Formaldehyde Resins . . . . 03

34.4 Polyurethane Resins . . . . 603

Malin Frick 34.4.1 Skin Problems from Polyurethane Resins . . 605 34.4.2 Patch Testing with Polyurethane Resins . . . 606

Suggested Reading . . . . 606

Plastic Materials Bert Björkner, Ann Pontén, Erik Zimerson, Malin Frick 34 34.5 Other Plastics . . . . 607

Bert Björkner 34.5.1 Amino Plastics . . . . 607

34.5.1.1 Skin Problems from Amino Plastics . . . . . 607

34.5.2 Polyester Resins . . . . 607

34.5.2.1 Skin Problems from Polyester Resins . . . . 608

34.5.3 Polyvinyl Resins . . . . 608

34.5.3.1 Skin Problems from Polyvinyl Resins . . . . 609

34.5.4 Polystyrene . . . . 609

34.5.4.1 Skin Problems from Polystyrene Resins . . . 609

34.5.5 Polyolefins . . . . 609

34.5.5.1 Skin Problems from Polyolefins . . . . 610

34.5.6 Polyamides . . . . 610

34.5.6.1 Skin Problems from Polyamides . . . . 610

34.5.7 Polycarbonates . . . . 610

34.5.7.1 Skin Problems from Polycarbonates . . . . . 610

34.5.8 Rare Plastic Materials . . . . 610

34.6 Plasticizers and other Additives in Synthetic Polymers . . . . 611

Bert Björkner 34.6.1 Plasticizers . . . . 611

34.6.2 Flame Retardants . . . . 611

34.6.3 Heat Stabilizers . . . . 611

34.6.4 Antioxidants . . . . 611

34.6.5 Ultraviolet Light Absorbers . . . . 611

34.6.6 Initiators . . . . 612

34.6.7 Curing Agents . . . . 612

34.6.8 Biocides . . . . 612

34.6.9 Colorants (Dyes and Pigments) . . . . 612

34.6.10 Metals and Metal Salts . . . . 612

34.6.11 Skin Problems from Additives . . . . 612

References . . . . 613

Introduction

One of the most important branches of the chemical industry is the polymer industry, which uses a wider variety of chemicals than any other sector. Plastic materials are more frequently used in daily living than ever before. Plastics come from oil and 5% of the total oil production in the world is used by the poly- mer industry. The number of commercially impor- tant plastics today is more than 50. Application areas for plastics are many and varied: the construction in- dustry, packaging, electronics, recreation, medical, etc.; 30% of base plastics are used for packaging and 20% are used in the construction industry.

There are several ways of classifying polymeric materials. Chemically, they are very large molecules (polymers) formed by the linking up of small mole- cules (monomers) into large chain-like units. If only one type of monomer is involved in forming the polymer, it is called a homopolymer. If two or more different types are involved, it is called a copolymer.

The words “plastic” and “resin” are often used syn- onymously. However, strictly speaking, plastics are synthetic macromolecular end products, while the term “resin” is used to denote all low-, medium-, and high-molecular-weight intermediate synthetic sub- stances from which plastics are made. Natural rub- bers and cellulose do not fit into these definitions be- cause their starting material is of natural origin and not synthetic.

If the monomers that form the final polymer sim- ply link up into long chains by joining bonds, and nothing is eliminated in the process, the polymeriza- tion is called an addition reaction. If two or more dif- ferent monomers react with each other, thereby elim- inating a simple molecule such as water, the poly- merization is called a condensation reaction.

Traditionally and practically, plastics can be divid- ed into three major categories: thermoplastic, ther- mosetting, and elastomers. The thermoplastic resins are characterized by softening when exposed to heat, and when soft, they can be made to flow and assume the desired shape. When cooled, they become hard again. Thermoplastic resins are made up of long mo- lecular chains unconnected with each other. When heated, the molecular chains become moveable and the plastic material melts, starts to float, and be- comes liquid. The thermoplastic resins, therefore, have different characteristics at different tempera- tures.

Thermosetting resins have chemical bonds between the long molecular chains. When heated for the first time, they, therefore, undergo further chem- ical reactions in which cross-links develop between

polymer chains, holding them rigid in the desired position. They do not soften on re-heating into the original polymer. Examples of thermoplastic resins are polyethylene, polystyrene, polyvinyl chloride, and saturated polyesters. Examples of thermosetting resins are phenol formaldehyde resins, epoxy resins, polyurethanes, unsaturated polyesters, and acrylates.

Synthetic rubbers are examples of elastomers.

The final plastic products, when completely cured or hardened, are generally considered to be inert and non-hazardous to the skin. Skin problems from plas- tics are almost exclusively related to ingredients such as monomers, hardeners, and other additives, or deg- radation products of low molecular weight.

34.1 Acrylic Resins

Bert Björkner

Acrylic resins are thermoplastics formed by deriva- tives of acrylic acid (CH

=CH-COOH). The acrylic group is a vinyl group (CH

=CH-). The monomers in acrylic resins are acrylic acid and methacrylic acid and their esters, cyanoacrylic acid and its esters, acrylamides, and acrylonitrile. Numerous different acrylic monomers, therefore, exist and, as a result, a multitude of different polymers and resins are pro- duced.

The polymerization of acrylic monomers is an ad- dition reaction obtained either at room temperature or by heating. Adding initiators, accelerators, and cat- alysts usually speeds up the process. Polymerization or curing can also be achieved by ultraviolet (UV) light, visible light, or electron beams (EB), for which initiators are not necessary.

34.1.1 Monoacrylates

and Monomethacrylates

Mono(meth)acrylates (monoacrylates and mono- methacrylates) are used in the production of a wide variety of polymers.

Polymethyl methacrylate is the most important plastic in the acrylics group, with the following re- peating unit: [CH

-CH(CH

)COOCH

]

. This plastic has excellent transparency and is, therefore, used in products such as roof windows, housewares, watch glasses, bags, lamp housings, and windscreens. A two-component system is used in the manufacture of dentures, hearing aids, noise protectors, and bone ce- ment in orthopedic surgery. The first component is a prepolymer powder of polymethyl methacrylate with benzoyl peroxide as an initiator. The second compo-

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Fig. 1.1.

Polymethyl methacrylate and methyl methacrylate mixed with sand are some- times used as flooring. Pro- tective gloves are recom- mended

Fig. 1.2. Chemical formulae of some monofunctional acrylate compounds in UV-curable acrylate-based paints and lacquers

nent is a monomeric liquid of methyl methacrylate containing an accelerator, e.g., N, N′-dimethyl-p-to- luidine. A two-component methyl methacrylate sys- tem mixed with sand is used in flooring (Fig. 1.1).

Other polymers of the mono(meth)acrylate type are mostly used in industry. Leather finishes, adhe- sives, paints, printing inks and coatings are example of practical applications. Butyl acrylate is sometimes used in spectacle frames. 2-Ethylhexyl acrylate is of- ten used in the manufacturer of pressure-sensitive adhesives, but a wide range of other acrylates are al- so used in this field.

The acrylic monomers preferred in the prepara- tion of UV-curable inks and coatings or in the photo- prepolymer printing plate procedure are 2-hydroxye- thyl acrylate (2-HEA), 2-hydroxypropyl acrylate (2- HPA), 2-hydroxypropyl methacrylate (2-HPMA), 2- hydroxyethyl methacrylate (2-HEMA), and 2-ethyl- hexyl acrylate (2-EHA) (Fig. 1.2). 2-HPMA is also used in light-sensitive compositions for fissure seal- ants/adhesives or bonding preparations in dentistry and in printing plates. Various mono(meth)acrylates can be used in water-based acrylic latex paints. Plas- tic dispersions of acrylic polymers are used as binders or thickeners in paints, as well as cosmetic creams.

Their monomer content is usually less than 0.3%.

34.1.2 Multifunctional Acrylates

Acrylates with at least two reactive acrylic groups are called multifunctional acrylates. These are, e.g., di(- meth)acrylate esters of dialcohols or tri- and tetra- acrylate esters of polyalcohols. Multifunctional acry-

lates are used in formulations for UV-curable inks and coatings, where they act as cross-linking agents and reactive diluents, and become a part of the final coating on UV exposure (Fig. 1.3). The multifunc- tional acrylates are also important in photopolymers, flexographic printing plates, and photoresists (an etch-resist for printed circuit boards). The multi- functional acrylate esters are useful in acrylic adhe- sives and anaerobic sealants, as well as in artificial nail preparations. Some of the more commonly used multifunctional acrylates for artificial nail prepara- tions are ethylene glycol dimethacrylate (EGDMA), diethylene glycol dimethacrylate (DEGDMA), and trimethylol propane trimethacrylate (TMPTMA).

The various acrylates used in acrylic nail prepara- tions are listed in Table 1.1 [1–5].

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Fig. 1.3.

UV-curable acrylic inks mixed with color pigments.

Protective gloves are highly recommended

Table 1.1. Acrylates used in acrylic nail preparations Methyl methacrylate

Ethyl methacrylate Ethyl acrylate

2-Hydroxyethyl acrylate Butyl methacrylate Isobutyl methacrylate Methacrylic acid

Tetrahydrofurfuryl methacrylate Ethylene glycol dimethacrylate Diethylene glycol dimethacrylate Triethylene glycol dimethacrylate Trimethylol propane trimethacrylate Urethane methacrylate

Tripropylene glycol acrylate

Most of the dental composite resin materials and denture base polymers are “diluted” with the less vis- cous, difunctional acrylates. These are the methacryl- ic monomers, of which EGDMA, DEGDMA, triethy- lene glycol dimethacrylate (TREGDMA) (Fig. 1.4), and 1,4-butanediol dimethacrylate (BUDMA) (Fig.

1.5) are the most widely used (Table 1.2). Acrylates used in dentistry are an expanding field. Some are al- so new to dermatology, but others are well-known sensitizers [6–8]. 1,6-Hexanediol diacrylate (HDDA) is used as a dental acrylate, but is a known sensitizer in the printing ink and coating fields (Fig. 1.5).

The simplest UV-curable ink or coating formula- tions may consist of only three components. In prac- tice, however, a typical industrial formulation con- tains a much greater number of ingredients. The three essential components are: a UV-reactive pre- polymer that provides the bulk of the desired proper- ties, a diluent system composed of multifunctional acrylate esters (and at times, monofunctional acrylic esters), and a photoinitiator system. The most com- monly used multifunctional acrylate in a UV-curable ink or coating formulation is an acrylic acid ester of either pentaerythritol (PETA), trimethylolpropane (TMPTA), or hexanediol (HDDA) (Figs. 1.5 and 1.6).

During the past 15–20 years, the use of UV-curable acrylates in inks and coatings has increased tremen- dously. In the can-coating industry, UV printing inks

Fig. 1.4.

Chemical formulae of n-eth- ylene glycol di(meth)acry- lates

Fig. 1.5.

Chemical formulae of 1,6- hexandiol diacrylate and 1,4- butandiol dimethacrylate

Table 1.2. Acrylic compounds used in dental materials Methyl methacrylate

Triethyleneglycol dimethacrylate Urethane dimethacrylate Ethyleneglycol dimethacrylate BIS-GMA

BIS-MA BIS-EMA BIS-PMA

2-(Dimethylamino)ethyl methacrylate Butyl methacrylate

2-Hydroxyethyl methacrylate 1,6-Hexanediol diacrylate 1,10-Decanediol dimethacrylate 1,4-Butanediol dimethacrylate 1,12-Dodecanediol dimethacrylate Trimethylolpropane trimethacrylate Phenylsalicylate glycidyl methacrylate Tetrahydrofurfuryl methacrylate Benzaldehyde glycol methacrylate N-Tolylglycine-glycidylmethacrylate 1,3-Butyleneglycol diacrylate

3,6-Dioxaoctamethylene dimethacrylate Biphenyl dimethacrylate

Glycerol phosphate dimethacrylate

are used on beverage and beer cans, as well as on crown caps and aerosol containers. UV-curable acry- late coatings are used as wood finishes, matt varnish- es, parquet varnishes and sealers, and as varnishes and coatings in the manufacture of furniture.

TMPTA and PETA can both be used in the produc- tion of polyfunctional aziridine, added to paint primer and floor top-coatings as a self-curing cross- linker or hardener [9–11].

In the absence of oxygen and in the presence of metals, anaerobic acrylic sealants, e.g., Loctite, Tree- bond, and Sta-Lok, polymerize rapidly. Dimethacry- lates are their principal components [7, 12–18]. Di- ethylene glycol dimethacrylate oligomer is most commonly used for screw-thread-locking, whereas urethane dimethacrylate is used for retaining and locking flat metal surfaces.

34.1.3 Prepolymers

Acrylate resins, based on the conventional thermo- plastic resins, into which two or more reactive acry- late or methacrylate groups have been introduced, are called prepolymers. The most commonly used prepolymers are acrylated epoxy resins, acrylated polyurethanes, acrylated polyesters, and acrylated polyethers.

쐽 UV-curable acrylic compounds contain three basic components: a reactive base prepolymer, a diluent system of multifunc- tional acrylic esters, and a photoinitiator system.

34.1.4 Epoxy Acrylates

Epoxy acrylate is another name for beta-hydroxy- ester acrylate, since it is usually obtained by reacting epoxy resins or glycidyl derivatives with acrylic acid (Fig. 1.7). Both aromatic or aliphatic epoxy acrylates are available, as well as acrylated epoxydized oils.

Epoxy acrylates have found a wide range of useful applications in UV- or EB-curing.

The addition-reaction product between bisphenol A and glycidyl methacrylate or an epoxy resin and methacrylic acid is BIS-GMA; 2,2-bis[4-(2-hydroxy- 3-methacryloxypropoxy)phenyl]propane (Fig. 1.7).

BIS-GMA can, therefore, be classified as a dimethac- rylated epoxy, although it does not contain a reactive epoxy group. BIS-GMA is the most commonly used prepolymer in dental composite restorative materi- als.

Several similar compounds have also appeared as substitutes for BIS-GMA or in addition to BIS-GMA in dental resins (Table 1.2). Such dimethacrylates based on bisphenol A with various chain lengths are BIS-MA; 2,2-bis[4-(methacryloxy)phenyl]-propane and BIS-EMA; 2,2-bis[4-(2-methacryloxyethoxy)- phenyl]-propane and BIS-PMA; 2,2-bis[4-(3-meth- acryloxypropoxy)phenyl]-propane (Fig. 1.7).

The industrial applications of BIS-GMA resins and other similar derivatives are extensive. Acrylates based on bisphenol A or epoxy resin can be polymer- ized not only by exposure to EB, UV-light, or even visible light, but can also be chemically activated by the use of various peroxides.

34.1.5 Urethane Acrylates

There are many types of acrylated urethanes on the market. While some are based on aromatic isocya- nates, others are of the aliphatic type. Acrylated ure- thanes are used not only in prepolymers in UV-cur- able inks or coatings, for instance vinyl floorings, but also as resins with dental applications. The acrylated urethanes used in dentistry are of the methacrylated type.

34.1.6 Polyester Acrylates

There are various types of polyester acrylates on the market and they are mostly used in UV-curable lac- quers and printing inks for wood and paper coatings.

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Core Message

Fig. 1.6. Chemical formulae of two common UV-curable mul-

tifunctional acrylates

Fig. 1.7. Chemical formulae of di(meth)acrylates based on bisphenol A and epoxy resin

34.1.7 The Effects of Acrylate Esters on the Skin

Evaluation of the irritant potential of various acrylic monomers has shown that the diacrylates are strong irritants, monoacrylates weak to moderate irritants, and monomethacrylates and dimethacrylates non- irritant or weak irritants to guinea-pig skin [19–27].

Multifunctional acrylates as well as acrylated prepol- ymers seem to be more irritating than the corre- sponding methacrylates. These effects have been seen when patch testing both humans and guinea pigs [27]. Bullous irritant skin reactions in workers exposed to tetramethylene glycol diacrylate have been reported [28]. A peculiar delayed irritation from butanediol diacrylate and hexanediol diacry- late has been observed by Malten et al. [29]. Tetraeth- ylene glycol diacrylate can cause delayed irritant re- actions as well as allergic contact dermatitis [30]. The irritant effect of various acrylate compounds has been reviewed by Kanerva et al. [31, 32].

The sensitizing potential of many mono(meth)- acrylates, multifunctional (meth)acrylates, and acry- lated resins in guinea pigs has been thoroughly stud- ied by numerous authors [19–27]. Tests have shown that monoacrylates are strong sensitizers while mono(meth)acrylates have weak to moderate sensi- tizing potential [19, 21, 23, 27]. Thus, the introduction of a methyl group reduces the sensitizing potential of monoacrylates. Of the multifunctional acrylates, the di- and triacrylic compounds should be regarded as potent sensitizers [22, 24, 27]. The methacrylated multifunctional acrylic compounds are weak sensi- tizers [24, 27].

Among the various di(meth)acrylates based on bisphenol A or epoxy resin, allergenicity seems to di- minish if the acrylates have three or more methylene groups in the molecular chain [22–27]. It is more dif- ficult to predict the sensitizing capacity of the vari- ous prepolymers. Epoxy acrylates are strong sensitiz- ers and their sensitizing capacity is due to the entire molecule, thereby, excluding the epoxide group as the sole sensitizing part of these compounds [27]. Free epoxy resin may be present in epoxy acrylates, which may sensitize separately or simultaneously [24, 33].

The whole molecular structure of polyester acry- late probably acts as an allergen as well. However, the reactive acrylate and methacrylate terminal groups seem to be of great importance for antigen formation and sensitization [25]. The carboxyethyl side group seems to be of importance for antigenicity [34].

The aliphatic urethane acrylates are more potent sensitizers than the aromatic ones, while the aliphat- ic urethane methacrylate commonly used in dental resins is a weak sensitizer [26, 35].

There are many reports of contact allergy to mono(meth)acrylates in humans. Contact dermatitis due to 2-HPMA in printers exposed to printing plates, as well as to UV-curing inks, has been report- ed [36, 37] (Fig. 1.8). Contact allergy to 2-HEMA, one of the ingredients in a photo prepolymer mixture, has been described [38]. 2-HEMA is a water-soluble form of methacrylate resin and is, therefore, com- monly used as a dentine-bonding compound. The bonding systems used contain a primer and an adhe- sive. Primer, followed by the adhesive, first coats the dentine. This is polymerized with a visible-light curing unit and then a dental composite resin is ap-

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Fig. 1.8.

A printer with contaminated

clothes mixing UV-curable

acrylics

plied to the tooth and cured chemically or with light.

2-HEMA is a common allergen in dental personnel (Fig. 1.9). Fingertip dermatitis is common in dentists and dental nurses allergic to dentine-bonding acry- lates [6, 39–42] (Figs. 1.10 and 1.11)

Contact dermatitis from 2-EHA in an acrylic- based adhesive tape has been reported [43]. Orthope-

dic surgeons, surgical technicians, nurses, and dental technicians are exposed to methyl methacrylate monomer when preparing bone cement and den- tures. Contact allergy to methyl methacrylate monomer is rare in patients undergoing hip surgery [44].

In recent decades, many reports of contact allergy caused by various multifunctional acrylic com- pounds have been published [6–8, 27, 45–47]. At risk of developing contact allergy to multifunctional tri- and diacrylates are those working with UV-curable inks or coatings, while contact allergy to dimethacry- lates is more commonly seen in dentistry, in those working with anaerobic acrylic sealants and in those exposed to acrylic nails [6, 7, 27, 39–42, 47–55]. In spite of that risk, epoxy acrylates are strong sensitizers in animal studies [27], allergic contact dermatitis caused by epoxy (di)methacrylates seems to be rare in workers exposed to ultraviolet-cured inks [56, 57]

There are some reports of allergic contact dermatitis from dimethacrylates based on bisphenol A or epoxy resin in dental composite materials. At risk of devel- oping contact dermatitis are dentists and dental technicians, as well as dental patients [6, 7, 39–42, 53–55]. Methacrylates have also caused asthma and rhinoconjunctivitis in dental personnel [50–52]. Pa- tients allergic to BIS-GMA may also react to epoxy resin MW 340 [24, 54, 58]. It is uncertain whether any residual epoxy resin monomer is left unreacted or whether it is formed in the synthesis of the BIS-GMA monomer [24, 33].

Methyl methacrylate and 2-HEMA can cause par- esthesia of the fingertips for months after discontin- uation of contact with the monomer [59–61]. An ef-

Fig. 1.9. Uncured acrylates that remain on the outside of a bot- tle used for dental bonding systems can cause fingertip derma- titis

Fig. 1.10.

Severe fingertip dermatitis

in a dentist with contact al-

lergy to acrylates used in

dentistry

fect on the peripheral nervous system has also been described for acrylamide [62] and cyanoacrylates (see later).

쐽 Free epoxy resin may be present in epoxy acrylates, which may sensitize separately or simultaneously.

34.1.8 Acrylonitrile

Acrylonitrile (H

C=CH-CN) is used as a copolymer in approximately 25% of all synthetic fibers. It is fur- ther used for synthetic rubbers and for the produc- tion of acrylonitrile-butadiene-styrene and styrene- acrylonitrile plastics. These ter- and copolymers are used in the automobile industry and in the produc- tion of housewares, electrical appliances, suitcases, food packaging, and disposable dishes. Acrylonitrile can also be a constituent in fabrics and paints.

34.1.9 Skin Problems from Acrylonitrile There are a few reports of contact allergy to the acry- lonitrile monomer [63–67]. In the guinea pig maxim- ization test, however, acrylonitrile has shown strong allergenic potential [67].

34.1.10 Acrylamide and Derivatives

Acrylamide (H

C=CH-CO-NH

) is an odorless, white, crystalline solid used as a monomer or as a raw material in the production of polyacrylamides and other compounds. Most of the acrylamide monomer is produced and used as an aqueous solution. The re- active acrylamide monomer is used in the produc- tion of other compounds, mostly polymers of acryla- mide, and as a grouting agent in the construction or rehabilitation of dams, buildings, sewers, tunnels, and other structures. Acrylamide grouts are used predominantly as barriers against ground-water seepage into sewers. About 95% of the acrylamide produced is consumed in the production of other compounds, including polyacrylamide products that are widely used as flocculents in potable water and waste-water treatment, mineral ore processing and sugar refining, water-flow control agents in oil-well operations, and adhesives in paper making and con- struction. The remaining 5% is used as a monomer.

Acrylamide and its derivatives are also used in the production of photopolymer printing plates. Because acrylamide is produced by catalytic or sulfuric acid hydration of acrylonitrile, acrylamide production workers may also be exposed to acrylonitrile.

34.1.11 Health Effects from Acrylamide and Derivatives

Polyacrylamide products are generally considered non-hazardous. The monomer can be irritating and

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Core Message

Fig. 1.11.

When grinding prosthesis,

uncured acrylates can cause

dermatitis in sensitized den-

tal personal

cause contact allergy. Skin problems are seen among printers exposed to photopolymerizing printing plates. Acrylamide and their acrylamide compounds N, N′-methylene-bis-acrylamide, N-methylol acryl- amide and N-[2-(diethylamino) ethyl] acrylamide have been described as allergens [68–76]. N-Methylol acrylamide sensitization has also been observed in workers making PVA-acrylic copolymers for paints.

Acrylamide, N-hydroxymethyl acrylamide and N,N′- methylene-bis-acrylamide are moderate sensitizers when tested in guinea pigs [20].

The acrylamide monomer may be neurotoxic, car- cinogenic, genotoxic, and hazardous to reproduction.

Recent studies confirm that acrylamide exposure causes cancer and has reproductive effects in ani- mals, but epidemiological studies have not demon- strated these effects in humans. The neurotoxic ef- fects from acrylamide exposure include peripheral nerve damage and central nervous system effects [62, 71–73].

Allergic contact dermatitis from piperazine di- acrylamide, used as a reagent and as a cross-linker for acrylamide gels in electrophoreses and column chromatography has been described by Wang et al.

[77].

쐽 The acrylamide monomer may be neurotoxic, carcinogenic, genotoxic, and hazardous to reproduction.

34.1.12 Cyanoacrylates

Cyanoacrylates (H

C=C(CN)-COOR) are also called

“super glues.” The structure of the side chain (R) defines the different alkyl 2-cyanoacrylates and is dependent on the alcohol that has been used. For instance, methanol gives methyl 2-cyanoacrylate, ethanol gives ethyl 2-cyanoacrylate, etc.

Methyl 2-cyanoacrylate is mainly used in instant glue for household use. Ethyl 2-cyanoacrylate is the most commonly used in industry and the most of the different adhesive products on the market are manu- factured by Loctite. n-Butyl 2-cyanoacrylate and iso- butyl 2-cyanoacrylate are commonly used in medical adhesives.

Glues based on cyanoacrylates are widely used as contact adhesives for metal, glass, rubber, plastics, and textiles, as well for biological materials, includ- ing binding tissues and sealing wounds in surgery.

The bonding action of cyanoacrylates is generally believed to be the result of an anionic polymerization that is highly exothermic and rapidly occurring, within seconds or minutes, even at room tempera- ture. Catalysts are not required for this reaction to occur, since weak bases, such as water and alcohols or nucleophilic groups on proteins, e.g., amine or hy- droxyl groups, already present on the adherent sur- faces initiate the polymerization.

Vaporized cyanoacrylates are known to irritate the eyes and respiratory tract. Irritation and discom- fort of the face and eyes may occur in workers due to associated low humidity [78, 79].

Contact sensitization to cyanoacrylates is consid- ered extremely rare, due to the immediate bonding of the cyanoacrylate to the surface keratin [78]. The ad- hesive was, therefore, believed to have never come into contact with immunocompetent cells deeper in the epidermis. For instance, Parker and Turk [21]

were unable to sensitize guinea pigs with methyl or butyl 2-cyanoacrylate. However, in the last decade, some case reports have been published which strong- ly indicate that cyanoacrylates are able to induce con- tact allergy [80–92].

Patch testing with cyanoacrylate glue might give false-negative reactions when dissolved in acetone using the Finn chamber (aluminum) technique.

Patch testing with petrolatum as the vehicle in a plas- tic chamber is recommended [87].

Cyanoacrylates, besides causing skin sensitization and irritation, have also been shown to cause occupa- tional asthma and to be mutagenic. Furthermore, cyanoacrylates are suspected to be carcinogenic and to induce peripheral neuropathy and onychodystro- phy [89–92] (Fig. 1.12).

34.1.13 Care in the Handling of Acrylic Resins

Gloves are recommended to protect the hands against the various acrylic compounds. Methyl me- thacrylate, as well as other acrylic monomers, such as butylacrylate and acrylamide, easily penetrates natu- ral rubber latex gloves, and vinyl gloves are even worse in this respect [20, 93–99]. Polyethylene gloves give the best protection against methyl methacrylate diffusion [20]. Nitrile gloves give better protection than neoprene gloves against UV-curable acrylate resins [94]. New multilayer glove material of the folio type, with ethylene-vinyl-alcohol copolymer lami- nated with polyethylene on both sides, has especially good chemical resistance [100]. The protective effect of gloves against acrylates in dentine-bonding sys- tems was tested on acrylate-sensitized patients and

Core Message

showed clear differences in the protective efficacy between types of gloves [96, 97]. Because acrylics used in dentine-bonding systems are strong sensitiz- ers and quickly penetrate most gloves, dentists and dental personnel should use no-touch techniques [6, 100].

As most of the acrylic compounds used in UV- curable acrylic resins should be regard as irritants and relatively potent sensitizers, care should, thus, be taken accordingly to minimize their contact with the skin.

Measures that seem effective in preventing the oc- currence of dermatitis include the use of imperme- able protective gloves and protective clothing. Face shields and goggles are recommended whenever there is a risk of splattering. The contaminated skin should be washed with soap and water and contami- nated clothing should be removed promptly. It is es- sential to separate clean from contaminated clothing.

Thorough education of employees regarding skin hazards is also recommended.

쐽 Because acrylics used in dentine-bonding systems are strong sensitizers and quickly penetrate most gloves, dentists and dental personnel should use no-touch techniques.

34.1.14 Patch Testing

with Acrylic Compounds

In general, a patch test concentration of 2% in petro- latum is recommended for methacrylated monomers and 0.1% in petrolatum for acrylated monomers, to avoid patch test sensitization [101]. A marked de- crease in the number of positive test responses has been noticed when acetone and alcohol has been used as the test vehicle for various acrylic com- pounds instead of petrolatum [87] The petrolatum vehicle probably prevents the acrylic monomers from polymerizing. A rapid polymerization of acryl- ic monomers was also seen when an aluminum test chamber was used instead of a plastic test chamber.

Aluminum oxide probably enhances the polymeriza- tion process [87]. When acrylic compounds are patch tested, it is, thus, recommended to use petrolatum as the test vehicle in a plastic test chamber.

Cross-reactions of multifunctional methacrylates and acrylates has been investigated by Kanerva [102]

and Rustemeyer et al. [103].

쐽 When acrylic compounds are patch tested, it is recommended to use petrolatum as the test vehicle in a plastic test chamber.

Bert Björkner 594

34

Core Message

Core Message

Fig. 1.12.

Onychodystrophy in a pa-

tient allergic to nail polish

based on cyanoacrylate

34.2 Epoxy Resin Systems

Ann Pontén

Epoxy resins and curing agents are the two mandato- ry components in epoxy resin systems. Additionally, epoxy resin systems may contain several types of modifiers and additives. The term “epoxy resin” is of- ten used to indicate the resins in both the thermo- plastic (uncured) and thermoset (cured) states [104].

쐽 Epoxy resin systems contain epoxy resins and hardeners and may contain modifiers and additives.

34.2.1 Epoxy Resins

Epoxy (or ethoxylin) resins contain at least two ep- oxy groups, also called oxirane or epoxide groups, in their molecules. The epoxy group is formed when two carbon and one oxygen atoms bind chemically.

The commercially most important epoxy resins are produced by polycondensation of compounds with at least two hydroxy groups and epichlorohydrin [104, 105].About 75–90% of epoxy resins are based on diglycidyl ether of the bisphenol A (DGEBA), formed by combining epichlorohydrin and bisphenol A [synonyms: 4,4′-(1-methylethylidene)bisphenol; 4,4′- isopropylidenediphenol; 2,2- bis(4-hydroxyphenyl)- propane] [104, 105]. DGEBA resins were first synthe- sized in the late 1930s. When the proportion of epi- chlorohydrin and bisphenol A is varied during the manufacturing process, different amounts of low- and high-molecular-weight (MW) resins are formed.

The general chemical structure of DGEBA resin is

shown in Fig. 1.13. The repeating part of the resin molecule has MW 284.When n=0 (Fig.1.13),an epoxy resin containing only the monomer DGEBA with MW 340 is obtained. Low-MW epoxy resins are sem- isolid or liquid and have an average MW of less than 900, and a large amount of the monomer DGEBA.

Resins with an average MW of more than 900 are sol- ids, but may contain more than 15% DGEBA [106, 107]. Commercial epoxy resins are, thus, mixtures of oligomers of different MWs, 340 (n=0), 624 (n=1), 908 ( n=2), 1,192 (n=3), etc. Components such as colorants, fillers, tar, UV-light absorbers, flame retar- dants, solvents, reinforcement agents, and plasticiz- ers can also be added to the raw materials. Epoxy res- ins may also be blended with formaldehyde resins based on phenol, urea, and melamine.

The total world production of epoxy resins is ap- proximately 1,000,000 tons a year. Epoxy resin sys- tems are used in the casting of models and in elec- tron microscopy, as a glue for metal, rubber, plastics, and ceramics, electric insulation, floor covering, cor- rosion protection of metals, mending of cracks and fissures both in concrete and emeralds, for laminates, composites, and adhesives. About 40–50% is used in coatings. High-molecular solid epoxy resins in vari- ous solvents and solventless low-molecular liquid ep- oxy resins are used for painting, while solid resins in powder paints are used for electrostatic hard-coating of metal.

When great strength is required, fibers made from carbon, glass, nylon, etc. impregnated with epoxy res- in systems are increasingly used as composite mate- rials. Difficulties are encountered, however, with ad- herence to carbon fibers with DGEBA resins. Epoxy resins based on other epoxy compounds than DGE- BA have, thus, been developed. Examples are tetra- glycidyl-4,4 ′-methylenediaaniline (TGMDA), trigly- cidyl p-aminophenol (TGPAP), and o-diglycidyl phthalate. Applications in which pre-impregnated glass fibers (“prepreg”) can be used are the aircraft industry, the manufacture of electronic circuit

Fig. 1.13. Diglycidylether of bisphenol A (DGEBA) epoxy resin

Core Message

boards, and wind turbine rotor blades [108–111].

When needed, diglycidyl ether of tetrabromo-bis- phenol A (4Br-DGEBA) is often used as a flame retar- dant.

Instead of bisphenol A, bisphenol F or phenolic novolak resins can be used for the manufacture of epoxy resins. The monomers of these resins are the three isomers of diglycidyl ether of bisphenol F (DGEBF). The DGEBF resins can be mixed with DGEBA resins and have improved chemical and physical resistance [110]. Other polyhydroxy com- pounds can also be used, e.g., resorcinol, glycerol, ethylene glycol, pentaerythritol, and trimethylolpro- pane. Aliphatic epoxy resins are constituents of paints. Cycloaliphatic epoxy resin can occur in neat oils and jet aviation hydraulic fluid [112, 113].

Triglycidyl isocyanate (TGIC) and terephthalic ac- id diglycidylester are epoxy compounds that may be present in polyester powder paints (see Sect. 34.6) [114–116].

Epoxy acrylates can be obtained by reacting epoxy resin with acrylic acid and, generally, do not contain reactive epoxy groups. They are commonly used as prepolymers in UV-curable printing inks and coat- ings. Both aromatic and aliphatic epoxy acrylates are available, as well as acrylated epoxidized oils (see Sect. 34.1.4).

34.2.2 Hardeners

Hardeners (curing agents) react with the epoxy groups of the resin and are incorporated in the mo- lecular network. Catalytic curing agents are added in small quantities and act as a catalytic agent for react- ing the epoxy groups with one another, as accelera- tors and co-curing agents, or as activators [117]. The thermoplastic epoxy resins can be cross-linked through the use of a variety of hardeners to form thermoset plastics with insoluble three-dimensional structures. When epoxy resins are used in two-com- ponent products, the hardeners are added to the res- ins immediately preceding the application, and the subsequent cross-linking occurs at either ambient or elevated temperatures. One-component products contain latent curing agents which are inactive at normal storage temperatures, but which initiate cross-linking when heated. Examples of one-compo- nent epoxy products include powder paints and spe- cial adhesives.

There are many curing agents on the market. In Table 2.1, the commonly used hardeners are listed.

The hardeners used in cold-curing are mostly poly- amines, polyamides, or isocyanates, and those used

Ann Pontén 596

34

Table 2.1. Commonly used hardeners and catalysts (compiled using [117, 118])

Aliphatic amines and derivatives Ethylenediamine (EDA) Diethylenetriamine (DETA) Triethylenetetramine (TETA) Tetraethylenepentamine (TEPA) Dipropylenetriamine (DPTA) Diethylaminopropylamine (DEAPA) 3-Dimethylaminopropylamine (DMAPA) Trimethylhexamethylenediamine (TMDA) Cycloaliphatic polyamines

Isophoronediamine (IPDA) N-Aminoethylpiperazine

3,3 ′-Dimethyl-4,4′-diaminodicyclohexylmethane Menthanediamine

4,4 ′-Diaminodicyclohexyl methane Aromatic amines

N, N-Dimethylbenzylamine

4,4 ′-Diaminodiphenylmethane (DDM)=4,4′-Methylene dianiline (MDA)

m-Phenylenediamine (MPDA)

4,4 ′-Diaminodiphenylsulphone (DDS)=bis (4-amino phenylsulphone); (Dapsone)

3,3 ′-Diaminodiphenyl sulfone

2,4,6-Tris-(dimethylaminomethyl)phenol m-Xylylenediamine

Polyaminoamides

Condensation products of ethyleneamines and carboxylic acids

Adducts

Based on the reaction between aliphatic or aromatic amines and epoxy resin, epoxy-reactive diluents, ethylene oxide, etc.

Acid anhydrides

Phthalic anhydride (PA) Maleic anhydride (MA)

Hexahydrophthalic anhydride (HHPA) Methyl nadic anhydride

Tetrahydrophthalic anhydride (THPA) Methyltetrahydrophthalic anhydride (MTHPA) Methylhexahydrophthalic anhydride (MHHPA) Trimellitic anhydride (TMA)

Miscellaneous

Cyanoguanidine (DICY) Di- and polyisocyanates Polymercaptans Polyphenols Phenolic novolaks Cresol novolaks

Urea formaldehyde resins Melamine formaldehyde resins 1,3,5-Triglycidyl isocyanurate

Terephthalic acid diglycidylester

Trimellitic acid triglycidylester

a

Epoxy compounds in polyester resin systems

for thermal curing are carboxylic acids and anhy- drides or aldehyde condensation products, e.g., phe- nol-formaldehyde resins, melamine-formaldehyde resins, and urea-formaldehyde resins. Aliphatic and cycloaliphatic amines are low-viscosity liquids that react readily with epoxy resins at ambient tempera- tures; less reactive aromatic amines require an ele- vated curing temperature [104]. Examples of harden- ers for composite epoxy resins are methyl nadic an- hydride, N,N-dimethylbenzylamine, 4,4′-diamino- diphenyl sulfone (DDS), and dicyandiamide (DICY) [117]. Accelerators, e.g., tertiary amines, can be added to speed up the polymerization of epoxy resins. An example is 2,4,6-tris-(dimethylaminomethyl)phenol [117, 118]. Hexavalent chromate may be present in ac- celerators of the epoxy resin system [118].

34.2.3 Epoxy-Reactive Diluents

Reactive diluents are used to modify epoxy resins, principally by reducing their viscosity. They contain one or more epoxide groups that react with the har- dener at approximately the same rate as the resin.

Most of the reactive diluents on the market are used in the cold-curing process. They are blended in with commercial epoxy resin at a concentration of 10–30%

[119–121]. The epoxy-reactive diluents are generally glycidyl ethers, but sometimes, are glycidyl esters of aliphatic or aromatic structure. Aliphatic reactive diluents include compounds as 1,4-butanediol digly- cidyl ether, n-butyl glycidyl ether (BGE), allyl glyci- dyl ether, or other alkyl glycidyl ethers with longer carbon chains (C

–C

), e.g., epoxide 7 and epoxide 8.

Examples of aromatic reactive diluents are phenyl glycidyl ether (PGE) and cresyl glycidyl ether (CGE) [119, 121].

34.2.4 Skin Hazards

from Epoxy Resin Systems

Epoxy resin systems have been found to be one of the most frequent causes of occupational allergic contact dermatitis [121–124]. Most recorded cases were sensi- tized to DGEBA resins. In a study performed in an epoxy-based construction industry, it was found that 16.4% of the workers had acquired occupational con- tact allergy to ERS after one year of employment [125]. An epidemic of occupational contact allergy was caused by DGEBA resin in an immersion oil for microscopy [126].

쐽 Epoxy resin systems are important occupational contact allergens.

Alkaline hardeners were first considered to be re- sponsible for most of the cases of dermatitis ob- served during the handling of the DGEBA-based res- in systems in the 1950s, but later, the resin was identi- fied as the main cause [127, 128]. Gaul [129, 130] sus- pected that bisphenol A was the sensitizer of the res- in, whereas Calnan [131] believed that the epoxy group of epichlorohydrin was more likely to be re- sponsible for contact allergy. In 1977, Fregert and Thorgeirsson [132, 133] finally confirmed that the main sensitizer was the DGEBA monomer with a MW of 340. In the guinea pig maximization test, the oligomer with a MW of 624 was also a sensitizer, but was considerably weaker than the MW 340 oligomer.

The sensitizing capacity of epoxy resin decreases as the average MW increases [132–134]. In many cases, allergic epoxy dermatitis develops after accidental contact with epoxy resin, and frequent causative agents for epoxy dermatitis are paints and the raw material for paint [124, 135]. However, it is not unusu- al to find a positive patch test reaction to DGEBA res- in where the cause of the sensitization is unknown.

Dermatitis caused by epoxy resin systems is localized mostly to the hands and forearms, but sometimes the face is also involved. If the face and eyelids are in- volved, the dermatitis may be caused by airborne ex- posure to hardeners or reactive diluents. These com- pounds are very volatile compared to epoxy resin [136].

High MW epoxy resin in solvents for painting or epoxy resin powder for electrostatic coating of met- als are thought to rarely cause sensitization because of the low content of MW 340 oligomer. However, chemical analyses have shown that a solid epoxy res- in, which was not declared as a sensitizer, contained 18% DGEBA [107].

Even if the epoxy resin system is believed to be cured, up to 25% of monomers can remain non-hard- ened, particularly when cured at room temperature [109]. When DGEBA resins are cured by polyamine hardeners at room temperature, the amounts of un- reacted DGEBA or polyamine decrease rapidly with- in 1 or 2 days, but, thereafter, the decrease is slow.

Nevertheless, after 1-week’s cure, 0.02–12% of free DGEBA and 0.01–1% of free diethylenetriamine (DE- TA) were found when six different epoxy resin prod- ucts were experimentally cured by DETA [121]. Aller- gic contact dermatitis may, thus, be elicited in previ-

Core Message

ously sensitized individuals. Traces of nonhardened epoxy resin have been found in twist-off caps, film cassettes, furniture, metal pieces, signboards, textile labels, stoma pouches, polyvinylchloride plastic, na- sal cannulas, hemodialysis sets, cardiac pacemakers, fiberglass, brass door knobs, and tool handles, among other products [137]. Recent reports involve bowl polish and a bus pass [138, 139]. Epoxy-by-proxy dermatitis is also a possibility [140].

Fregert and Trulsson have described methods used for detecting the presence of epoxy resins of the bisphenol A type [137, 141] (see Sect. 25.1). The thin- layer chromatography method described for DGEBA has 150–200 times lower sensitivity for DGEBF [107].

Non-DGEBA epoxy resins are also potential caus- es of allergic contact dermatitis. The monomers of epoxy resins of the DGEBF type are strong sensitiz- ers and cross-react to a high degree with DGEBA in animal studies [142], and many patients simultane- ously react to both DGEBA and DGEBF resins [143, 144]. A statistically significant association between contact allergy to DGEBA resin and fragrance mix has been found [145].

The composite epoxy resins based on o-diglycidyl phthalate, tetraglycidyl-4,4 ′-methylenedianiline (TGMDA), triglycidyl p-aminophenol (TGPAP), and 4Br-DGEBA are sensitizers in humans [108, 110].

Testing with DGEBA resin may not reveal contact al- lergy to the composite epoxy resin [108, 110, 134, 146].

In workers handling fiberglass or carbon fibers, irri- tant dermatitis can be induced by fiber fragments [111, 147].

Reactive diluents contain epoxy groups and are strong sensitizers that may or may not cross-react with epoxy resins [148, 149]. Several cases with con- tact allergy to reactive diluents have been described [150, 151]. Reactive diluents may cause airborne aller- gic contact dermatitis and also depigmentation [150, 152].

Occupational contact allergies can occur to epoxy compounds in products other than epoxy resin sys- tems, such as cycloaliphatic epoxy resin in neat oil and jet aviation hydraulic fluid and 2,3-epoxypropyl trimethyl ammonium chloride (EPTMAC) used in a starch modification factory [112, 113, 153].

Polyamine hardeners can be both sensitizers and irritants (Table 2.1) [32, 118, 154]. In patients with al- lergic contact dermatitis, isolated contact allergy to the hardeners of the epoxy resin systems is unusual, but may occur [118]. In an industrial investigation among workers exposed to epoxy resins systems, 30% of the workers had contact allergy exclusively to at least one hardener [125]. The most potent sensitiz- ers among the hardeners are the aliphatic poly- amines (Table 2.1) [109, 148, 155]. Cycloaliphatic poly-

amines are also strong sensitizers [118, 148, 154, 156–158], and reports on contact allergies to 2,4,6- tris-(dimethylaminomethyl)phenol and m-xylylene- diamine have been published [118, 159]. Hardeners of the polyaminoamide type are nonsensitizers, but may contain aliphatic amines. Amine-epoxy adducts can contain free amines, but no free DGEBA [106, 121]. Contact allergy to methylhexahydrophthalic an- hydride present in epoxy resin systems has been de- scribed [160].

Reports of contact allergy to bisphenol A are con- troversial. In a few studies, a high incidence of bi- sphenol A allergy was found among those sensitized to epoxy resin [130, 161]. Other investigators have not confirmed these results [162–164]. Bisphenol A has, however, been identified as a contact allergen in vinyl gloves [165, 166].

A rather high risk of sensitization to epichlorohy- drin has been reported for workers in plants manu- facturing epoxy resin [163, 164, 167].

Contact urticaria can be caused by DGEBA resin, the hardeners methylhexahydrophthalic anhydride and methyltetrahydrophthalic anhydride, as well as by aliphatic polyamine hardeners [124, 168–170].

Photosensitivity has been reported in relation to the heating of DGEBA resin [171] and the use of ep- oxy powder paints [172]. The photosensitivity has been suspected to be due to bisphenol A contained in the resin [171]. Persistent light reactivity has been found in mice photosensitized by bisphenol A [173].

34.2.5 Patch Testing

with Epoxy Resin Systems

Approximately 60–80% of the cases with contact al- lergy to epoxy resin systems are sensitized to DGEBA resin [125, 174]. A patch test with the low-molecular- weight epoxy resin containing a high amount of oli- gomer MW 340 is, thus, adequate in the majority of cases. It is recommended to patch test with the epoxy resin 1% in petrolatum and this allergen is included in most standard series. Even if DGEBA resin is non- irritating, other types of epoxy resins can be irri- tants. For the latter, a patch test concentration of 0.25–1% is recommended [110, 134, 143]. There are too many hardeners and reactive diluents on the market to be used in routine testing. However, if contact al- lergy to hardeners or reactive diluents is suspected, it is necessary to obtain information and samples from the manufacturer and to test the components of the epoxy resin system separately. The recommended test concentration for hardeners and reactive dilu- ents is 0.1–1% in petrolatum, acetone, or ethanol [118, 121].

Ann Pontén 598

34

쐽 Epoxy resin in the standard patch test series does not detect all contact allergies to epoxy resin systems

34.2.6 Preventive Measures when Handling Epoxy Resin Systems Workers handling epoxy resin systems should be in- formed of the risk of skin sensitization. The simulta- neous use of irritant chemicals, e.g., organic solvents and amine hardeners, increases the risk of sensitiza- tion. The highly alkaline amine hardeners can be re- placed by polyaminoamides or amine-epoxy ad- ducts; this reduces the irritability of the epoxy resin system. Management personnel as well as the work- ers who come into contact with epoxy resin systems should be advised to refrain from skin contact. Ap- proximately 95% of exposed workers report wearing the gloves as recommended; still, the frequency of occupational contact allergy is high [125]. The use of proper personal protective measures, especially care- ful hand protection and regular cleaning and mainte- nance of all contaminated equipment, should be im- perative (Fig. 2.1). Epoxy resins are able to penetrate plastic and rubber gloves. Only heavy-duty vinyl gloves provide sufficient protection [175]. Multilay-

ered glove material of folio type (4H gloves) has been shown to give even better protection against epoxy resins and the auxiliary compounds used with them [176]. Barrier creams have been reported to protect against epoxy resins from minutes to some hours [100, 177, 178]. To reduce the allergenic properties of DGEBA resins, the use of the MW 340 oligomer at the lowest possible concentration and the use of high MW reactive diluents is recommended. However, all epoxy resins should be regarded as potential sensitiz- ers, and, preferably, they should be marked with la- bels specifying the concentrations of epoxy com- pounds with low MW. In some countries, education prior to being allowed to work with epoxy resin sys- tems is mandatory.

Suggested Reading

Fregert S, Thorgeirsson A (1977) Patch testing with low molec- ular oligomers of epoxy resins in humans. Contact Derma- titis 3 : 301–303

When patients with contact allergy to epoxy resin in the stan- dard patch test series were patch tested with the isolated oligomers of an epoxy resin based on bisphenol A, all pa- tients with contact reacted to the monomer diglycidyl ether of bisphenol A (DGEBA) with molecular weight (MW) 340. No patient reacted to oligomers with higher MW. The results were in accordance with results from a guinea-pig maximization test published in the same year by the same authors. Thus, it was shown that, in the quan- titatively most important epoxy resin on the market, the monomer DGEBA was the main allergen. These results still hold true.

Fig. 2.1a–c.

Contamination in the epoxy

industry a

Core Message

34.3 Phenol-Formaldehyde Resins

Er ik Z imerson

Phenol-formaldehyde resins (phenolic resins) are polycondensation products of phenols and alde- hydes, in particular, phenol and formaldehyde. They are divided into resols and novolaks. When phenol reacts with an excess of formaldehyde under alkaline

conditions, a resol resin is produced. As formalde- hyde is in excess in the process, various methylolphe- nol compounds are formed, such as monomers, dim- ers, and molecules of higher molecular weight. The base-catalyzed polycondensation of the products is stopped deliberately before complete curing. During processing, the polycondensation can be restarted by heating to achieve curing of the resin. This means that the resols are self-cross-linking and can be con- sidered as prepolymers. [179, 180].

Erik Zimerson 600

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Fig. 2.1b, c.

c

b

Novolak resins are formed when formaldehyde reacts with an excess of phenols under acidic condi- tions. Mainly, dimers such as dihydroxydiphenylme- thanes (bisphenol F isomers) are formed, but also are trimers and molecules of higher molecular weight.

However, the formed molecules in this case have no or few methylol groups. The novolaks can only be cured by the addition of curing agents, such as for- maldehyde, paraformaldehyde, or hexamethylenetet- ramine, in addition to heating. The cured polymer for both novolaks and resols is called resite or C- stage resin [179, 180].

Commercially available phenol-formaldehyde res- ins are most commonly based on phenol itself, but other phenols such as cresols, xylenols, resorcinol (1,3-dihydroxybenzene), bisphenol A (4,4 ′-isopropy- lidenediphenol), p-tert-butylphenol, 4-isooctylphe- nol, and 4-nonylphenol can be used. Besides formal- dehyde, other aldehydes, e.g., acetaldehyde, glyoxal, and furfural (2-furancarboxaldehyde) can also be used [179, 180]. Phenolic resins are available as solids (fragments, flakes, pastilles, or granules), or as solu- tions and liquids [180].

Phenol-formaldehyde and p-tert-butylphenol-for- maldehyde resins still have many industrial applica- tions, although other plastics nowadays have re- placed the use of these resins in many applications.

Glues and glue films based on phenol-formaldehyde resins are used in the plywood industry. Because of their moisture resistance, the glues and laminates are used in the building industry, and in boat and air- craft construction. The resins are also good insula- tors against electricity; they are thus used in elec- tronic and electric appliances. In addition, they can be used for the production of decorative laminates and coatings, and to coat rigid constructions, e.g., pipelines and reaction vessels, because of their high chemical resistance. They are also used as binders for glass and mineral fibers in the production of heat-, noise-, and fire-insulating materials, as well as in foundry molding sand and abrasives, such as sandpa- per, abrasive cloth, and flexible sanding discs. Novo- lak resins can be used in the production of grinding wheels, brake linings, and clutch facings. They are al- so used as raw materials for polyfunctional epoxy resins [179–181].

p-tert-Butylphenol-formaldehyde resins are used in adhesives based on neoprene and other rubbers.

These adhesives can be used in shoes, leather prod- ucts, automobile interior upholstery, furniture, adhe- sive tapes and labels, and in the gluing of certain floor coverings [179, 180]. p-tert-Butylphenol-formal- dehyde resins are also used as adhesives for leather, artificial fingernails, and labels.

The third largest group is phenolic resins modi- fied by natural resins. Rosin-modified phenolic res- ins are used as binders for book offset-printing inks [179].

34.3.1 Skin Hazards

from Phenol-Formaldehyde Resins The adverse effects in workers handling phenol- formaldehyde resins are mostly skin problems. Con- tact dermatitis is common and is usually caused by the development of contact allergy. Most of the re- ported cases of contact dermatitis are due to sensiti- zation to p-tert-butylphenol-formaldehyde resins.

Reviews on p-tert-butylphenol-formaldehyde resin- induced occupational eczema have been published [179, 182–184]. In general, population allergy frequen- cies of 0.5–2.1% are reported from different Europe- an countries [185–187].

Many of the substances found in p-tert-butylphe- nol-formaldehyde resin are allergens. However, patch testing with dilution series of components from the resin in sensitized patients and sensitization studies in animals have shown that the methylol-substituted dimers, 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-3- hydroxymethyl-benzyloxymethyl)-6-hydroxymethyl- phenol (Fig. 3.1a), and 4- tert-butyl-2-(5-tert-butyl-2- hydroxy-3-benzyloxymethyl)-6-hydroxymethyl-phe- nol (Fig. 3.1b) are major sensitizers in this type of res- in [188, 189]. Among the monomers 2,6-dimethylol- p-tert-butylphenol (Fig. 3.1c) and 5-tert-butyl-2-hy- droxy-3-hydroxymethyl-benzaldehyde (Fig. 3.1d) are considered to be the most important allergens [190–193]. The strong sensitizer p-tert-butylcatechol (Fig. 3.1e) has been shown to be present in p-tert-bu- tylphenol-formaldehyde resin and to be of relevance considering allergic reactions to this resin. p-tert-Bu- tylcatechol is also an antioxidant used as a stabilizer for a number of other monomers used in the produc- tion of plastics . The raw materials for the production of p-tert-butylphenol-formaldehyde resin are for- maldehyde and p- tert-butylphenol (Fig. 3.1f, PTBP).

Few patients allergic to p- tert-butylphenol-formal- dehyde resin are reported to react positively to the raw materials, indicating that these substances are not important allergens in the resin [191, 194]. How- ever, guinea pigs sensitized to p-tert-butylcatechol showed cross-reactions when tested with p-tert-bu- tylphenol [195].

The allergens in resins based on phenol and for-

maldehyde have also been investigated, and several

substances among the monomers and the dimers

have been shown to be allergens. Methylol-substitut-

Erik Zimerson 602

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Fig. 3.1a–r. Chemical structures of allergens in p- tert-butyl- phenol-formaldehyde resin (a–f), phenol-formaldehyde resin (g–n) and substances which are cross-reactors in patients al- lergic to phenol-formaldehyde resin (o–r). a 4- tert-Butyl-2-(5- tert-butyl-2-hydroxy-3-hydroxymethyl-benzyloxymethyl)-6- hydroxymethyl-phenol; b 4- tert-butyl-2-(5-tert-butyl-2-hy- droxy-3-benzyloxymethyl)-6-hydroxymethyl-phenol; c 2,6-di- methylol- p-tert-butylphenol; d 5- tert-butyl-2-hydroxy-3-hy-

droxymethyl-benzaldehyde; e p-tert-butylcatechol; f p-tert- butylphenol; g 4,4 ′-dihydroxy-3,3′-dihydroxymethyl-diphe- nylmethane; h 4,4 ′-dihydroxy-3-hydroxymethyl-diphenylme- thane; i 2-methylolphenol; j 4-methylolphenol; k 2,4-dimethy- lolphenol; l 2,6-dimethylolphenol; m 2,4,6-trimethylolphenol;

n o-cresol; o p-cresol; p salicylaldehyde; q 2,4-dimethylphenol;

r 2,6-dimethylphenol a

c

g

i j k l m

n o p q r

h

d e f

b

ed dimers were found to be major allergens in these resins, such as 4,4′-dihydroxy-3,3′-dihydroxymethyl- diphenylmethane (Fig. 3.1g) and 4,4 ′-dihydroxy-3- hydroxymethyl-diphenylmethane (Fig. 3.1h). Exam- ples of allergens among the monomers are 2-methyl- olphenol (Fig. 3.1l), 4-methylolphenol (Fig. 3.1j), 2,4- dimethylolphenol (Fig. 3.1k), 2,6-dimethylolphenol (Fig. 3.1l), 2,4,6-trimethylolphenol (Fig. 3.1m), and o- cresol (Fig. 3.1n). The monomers were, however, weaker allergens than the dimers. [179, 196–203]. A patch test study in patients with contact allergy to phenol-formaldehyde resin indicates that p-cresol (Fig. 3.1o), salicylaldehyde (Fig. 3.1p), 2,4-dimethyl- phenol (Fig. 3.1q), and 2,6-dimethylphenol (Fig. 3.1r) are cross-reacting substances, possibly after meta- bolic conversion into the corresponding methylol- phenols in the skin. The observed cross-reactions can indicate a connection between allergy to phenol- formaldehyde resin and tar as the methylphenols (Fig. 3.1n, o, q, and r) can be found in tar [204].

Formaldehyde is not the main sensitizer in phenol- formaldehyde resins [194]. Simultaneous reactions to phenol-formaldehyde resins, colophony/hydroxy- abietyl alcohol, and balsam of Peru/fragrance mix may occur [205].

Phenol-formaldehyde resins may also irritate the skin and cause chemical burns and depigmentation.

Phenols and aldehydes are primary skin irritants and concentrated phenol may even cause corrosive chemical burns. Besides being a potent sensitizer, formaldehyde is also a skin irritant.

Irritant contact dermatitis has been reported in the manufacture of an electric insulation material (Bakelite), which is phenol-formaldehyde resin made of incompletely condensed resin powder in molds [206]. Irritant contact dermatitis was also common among workers in the manufacture of decorative laminates made of paper sheets impregnated with phenol-formaldehyde resins [194, 207].

Immediate contact reactions to p-tert-butylphe- nol-formaldehyde resin have also been reported [208, 209].

34.3.2 Patch Testing

with Phenol-Formaldehyde Resins In addition to p-tert-butylphenol-formaldehyde res- in, it is also necessary to patch test with the actual resin to which the worker is exposed, as there is no single reliable test substance to detect allergy to the wide variety of phenolic resin types. Bruze found 2.5 times more patients with contact allergy to phe- nol-formaldehyde resins when routinely patch test- ing with a resin based on phenol and formaldehyde

(P-F-R-2) in addition to p-tert-butylphenol-formal- dehyde resin [210].

When detecting contact allergy to p-tert-butyl- phenol-formaldehyde resin in patients for whom no clinically relevant contact with the resin can be found, the possibility of p-tert-butylcatechol as the eliciting factor should be considered and patch test- ing with this substance should be performed when indicated. However, due to observed active sensitiza- tion when using a patch test concentration of 1% p- tert-butylcatechol in pet.,Estlander et al.recommend a lower concentration of 0.25% pet. [211].

34.4 Polyurethane Resins

Malin Fr ick

Polyurethanes (PUR) are plastics formed by addition reaction between isocyanates with di- or polyfunc- tionality and polyhydroxy compounds (polyols).

When one or both components are polyfunctional, the PUR polymer cross-links and thermosetting end products are produced. However, if both components are only difunctional, the PUR polymer can have a linear arrangement that does not cross-link, result- ing in a thermoplastic product. The polyols used are mainly polyesters or polyethers, but isocyanates can also react with other molecules if they carry active hydroxyl groups, such as, for example, water and amines. Isocyanates are low-molecular-weight aro- matic, aliphatic, or cycloaliphatic compounds which are characterized by a highly reactive -N=C=O group. Some diisocyanates used in the production of polyurethane products are shown in Fig. 4.1. Aromat- ic diisocyanates dominate the market, but since they undergo oxidative discoloration upon exposure to light and moisture, aliphatic isocyanates are used in applications that are exposed to a lot of light [212].

The most commonly used aromatic diisocyanate is

diphenylmethane diisocyanate (MDI), followed by

toluene diisocyanate (TDI). They are frequently used

in the production of rigid and flexible foam, but are

also used in coatings, adhesives, binders, and elasto-

mers. Technical qualities of MDI used in industry

contain a complex mixture of 25–80% monomeric

4,4 ′-MDI and oligomers containing 3–6 rings, as well

as other minor monomeric isomers, such as 2,4 ′-MDI

and 2,2 ′-MDI (Fig. 4.1). The exact composition varies

with the manufacturer [213]. These mixtures are usu-

ally referred to as polymeric MDI (PMDI), but the

synonyms crude MDI and polymethylene polyphen-

yl isocyanate (PAPI or PMPPI) are also used. Phenyl

isocyanate can be a contaminant in PMDI. TDI is in-

dustrially available as mixtures of the isomers 2,4-

Malin Frick 604

34

Fig. 4.1. Chemical formulae of various isocyanates used in the production of polyurethane plastics

TDI and 2,6-TDI in the ratio 80 : 20 or 65 : 35 (2,4 : 2,6), or as pure 2,4-TDI. Due to their light and weather resistance, the aliphatic diisocyanates 1,6- hexamethylene diisocyanate (HDI) and isophorone diisocyanate (IPDI) is commonly used in lacquers, coatings, and paints. Industrially, they are often used as modified higher molecular weight polyisocya- nates (biuret or isocyanurate derivatives) to decrease their volatility [214]. Examples of other diisocyanates used in special products include trimethyl hexa- methylene diisocyanate (TMDI), which is a mixture of the two isomers 2,2,4-TMDI and 2,4,4-TMDI, naphthalene diisocyanate (NDI), triphenylmethane triisocyanate (TPMTI), and dicyclohexylmethane diisocyanate (DMDI) [68, 79, 215]. When producing diisocyanates monomers, the corresponding di- amines are typically used as starting materials [214].

Many auxiliary substances are also used in the manufacture of PUR products. The hardening pro- cess can be modified by heat or with a catalyst, usual- ly tertiary amines and/or organometallics (primarily tin compounds) [216]. Other additives, e.g., fire re- tardants, fillers, coloring agents, and cross-linking agents, can be added to modify the polyurethane re- action, as well as the properties of the final product.

In the production of foamed plastics, blowing agents, e.g., pentane, carbon dioxide, or water, is also added [217].

In many applications, diisocyanates are used in a prepolymerized form. The prepolymers are pro- duced by mixing small amounts of di- or polyfunc- tional alcohols with an excess of isocyanate. This is done for reasons such as to add cross-linking, to modify the chemical reactivity of the isocyanate groups, or to decrease the volatility of the isocyanate, etc. [214]. In heat-setting applications, the isocyanate groups can also be blocked, i.e., temporarily inacti- vated. When heated, the blocking groups escape, thereby, releasing the isocyanate groups and ena- bling them to react [217]. When used as activators or hardeners, diisocyanates are often dissolved in ali- phatic or aromatic hydrocarbon solvents, or a mix- ture of different organic solvents, e.g., aliphatic hy- drocarbon solvents, petroleum, and butyl acetate.

Adhesives, varnishes, and paints may also contain solvents. Polyurethanes occur in many forms, such as coatings, paints, lacquers, adhesives (one- or two- component glue), binding agents, castings, elasto- mers, foams, fibers, and synthetic rubbers. Flexible polyurethane foams are used for mattresses, cush- ions, dashboards, and packages [215].

쐽 Polyurethanes (PUR) are formed by reacting a di- or polyfunctional isocyanate with a polyol in the presence of suitable catalysts and additives.

34.4.1 Skin Problems

from Polyurethane Resins

The main occupational hazard associated with PUR is the presence of isocyanates, which can cause asth- ma and rhinitis, hypersensitive pneumonitis or al- veolitis, conjunctivitis, and chronic obstructive lung diseases [218–220]. Isocyanates are considered toxic and poisonous chemicals [219].

Exposure to isocyanates may result in both aller- gic and irritant contact dermatitis, as well as urticar- ia [79, 221–225], and the typical localization are the hands and face. Diisocyanates are strong contact sen- sitizers, in accordance with the results of animal studies [226, 227]. Animal experiments have also shown that polyisocyanate prepolymers are capable of causing skin sensitization in guinea pigs [228].

However, in spite of this, reports on allergic contact dermatitis are few in number, considering the exten- sive use of these chemicals in manufacturing pro- cesses and other applications. The rigorous rules that the workers have to follow when working with poly- urethanes to minimize the hazardous effect of iso- cyanates on the respiratory tract have probably also decreased the amount of all forms of skin conditions.

Isocyanates are described as mild to strong irri- tants and irritant contact dermatitis seems to have been more common than allergic contact dermatitis [32]. Amine accelerators, e.g., diaminodiphenylme- thane (MDA), triethylenediamine, and triethylamine, can also cause skin irritation. Contact allergy to MDI, TDI, IPDI, HDI, TMDI, and DMDI have been report- ed [79, 215, 221, 222, 229–241]. Most recorded cases were sensitized to MDI or DMDI.

DMDI has been reported as a very potent sensitiz- er [229, 235, 242–245]. In a company manufacturing medical equipment, 13 out of 100 workers were sensi- tized to DMDI, which was used in a glue [235]. At a factory making car badges, two out of seven workers showed positive patch-test reactions to DMDI. It was also believed that irritant contact dermatitis from DMDI was the cause of three of the workers’ skin problems [229].

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