INTRODUCTION:

Acrylic resin is a material that is widely used in dental treatment particularly in orthodontics as well as prosthetics. Polymethylmethacrylate resins are frequently used in most dental practises as they are capable to provide the required properties and included with necessary criteria demanded by dental products. They are commonly used in the fabrication of temporary crowns, liners, variety of dental prosthesis as well as orthodontic appliances.

As acrylic based resins are able to provide the essential properties and have necessary characteristics for their use in diverse functions, they are frequently used in daily dental practice. Retention, support, and stability of removable prostheses can be re-established as denture liners are used to improve the fit of denture bases. Orthodontic appliances are used for space maintenance, tipping teeth, overbite reduction, block movements as well as retention.

Properties and functional values of acrylic resin-based products when use in oral cavity is depends on the endogenous factors as well as exogenous factors. The endogenous factors that is elicited by polymerization are degree of conversion of the monomers, the type of manipulation method and the condition of polymerization. Saliva, bacteria and mastication are the examples of exogenous factors (1). All these factors create a complex interactions, producing significant biological effect towards tissues of the oral cavity. The most common toxic effect on oral cell and tissues is biological which achieves a residual monomer that arise as a response to the polymerization process and due to biodegradation of dental materials within oral cavity.

Allergy is defined as a hypersensitivity reaction to an allergen that can be enhanced by repeated exposure to an allergen. People usually has immediate allergy reactions to different types of foods and drugs, however in case of allergy towards acrylic resin are less common and are commonly of delayed or contact allergy (2). The use of acrylic resin however elicited few adverse reactions such as allergic reaction, chemical irritation and a burning sensation in the mouth. The low cost, easily used and various applications of methyl methacrylate acrylic resins however are still used despite of allergic reactions that may appear after its applications.

Allergic reactions to acrylic resin are generally a localized events but presenting with different clinical presentations. The symptom may appear as lip swelling in case of allergy towards methyl methacrylate (3) and systemic involvement which is manifested by chronic urticaria (4). Usually the most common patient complaint related to methyl methacrylate acrylic resins is that a burning sensation in the mouth (5). The reaction may appear in the mucosa of the palate that is directly in contact with the upper dentures. Sometimes the reaction may be elicited in the region of tongue, buccal mucosa, and also oropharynx (6,7,8).

The main cause of allergic reaction could be due to leaching of residual monomer into the oral environment. Residual monomer contents are approximately 1.5% to 4.5% in self-curing acrylic resins (9) and about 0.3% in heat curing resins (10).

The allergic reactions to acrylics is described as type IV allergic reactions which takes place following exposure of subject to the allergen. The reactions appear due to presence of low molecular weight compound such as formaldehyde, benzyl peroxide, methyl methacrylate and plasticizers such as dibutyl phthalate that are carried by a protein (10).

Contact dermatitis is one of the reactions elicited as the response to the use of acrylic resin. It can be allergic (type IV) and toxic non inflammatory cell injury. The allergy to dental resin-based materials occurs due to reaction elicited in the resin matrix like monomer thus proceed to adverse effects. Examples of adverse effects may be arose are the use of methyl methacrylate which is an acrylate monomer, common in orthodontic baseplates and dentures may cause allergy toxic. Besides, the use of 2-hydroxyethylmethacrylate that is commonly used in bonding materials and resin enforced glass ionomer cements has possible allergy as an adverse effect. Allergy cytotoxic is elicited by ethylene glycol dimethacrylate whereas urethane dimethacrylate cause allergy genotoxicity. Other than that triethylene glycol dimethacrylate, bisphenol A, Bis-DMA, Bis-GMA, Tinuvin P, Phtalates as well as formaldehyde has their own adverse effects such as allergy genotoxicity and xenoestrogen.

This study review the possible hazards of dental patients and clinician that are exposed to resin based materials when receiving and rendering treatment respectively involving the use of this material.

Chemical Characteristics of Dental Resin Materials:

Chemical structure of monomer is important to be acknowledged in order to be able to understand the biological effects of resin materials that are used by the dental clinicians and technicians.

Monomer is a small molecule that are able to become long polymeric chains during polymerization reaction. In dentistry, the monomers that are used can be mono, di, or multifunctional depending on the number of reactive methacrylic groups. Furthermore, they can be classified into aromatic or aliphatic origin. Increased degree of conversion as well as lower viscosity of material can be obtained by adding monomers with low molecular weight (11). Stable chain polymers can be formed in the process of polymerization reaction which is an addition reaction that joins the monomer together. In this reaction, the initiator is cleaved into free radicals in the beginning of the process which is activated by activators like light, chemical or heat. The activators’ involvement is crucial as it gives the energy to the initiator which is a main reason for the splitting of initiator into free radicals. Without activator, free radicals cannot be obtained. When the monomers are activated, they will be linked together, thus a three-dimensional network of chains are formed by a continuous splitting of double bonds and by adding more amount of monomer to the free electron end (12).

The polymerization process ends by a formation of a covalent bond by coupling of two developing chains together. The reaction is stopped when there is deficient monomer remaining in order to react or when the distance between the reacting molecules are long (11).

Influence of the Methods and Conditions of Polymerization on the Residual Monomer Content in Dental Acrylic Resins and Its Cytotoxicity:

Activation of an initiator such as benzoyl peroxide is required for the polymerization of a PMMA-based dental resin which is an addition reaction. It later can be decomposed by different methods such as heat polymerization, or microwave polymerization or by addition of a chemical activator such as dimethyl-p-toluidine. Polymerization occur first followed by conversion of methyl methacrylate MMA to PMMA which is known as a curing process. Not all the monomers are converted to polymers during the polymerization reaction of acrylic resins. The leftover unreacted monomers are called residual monomers. Methods and conditions of polymerization may affect the concentration (13).

As the residual monomer is left in the polymer or may leach into water, the leach material is considered to be responsible for the various levels of in vitro toxicity. Powder to liquid ratio, storage time, the method of polymerization as well as cycle may cause cytotoxic effect of denture base acrylic resins.

Residual Monomer as a Consequence of Biodegradation:

Most of the reported issues related to clinical application of acrylic based resins is their biodegradation. Biodegradation can be defined as the changes of their chemical, physical and mechanical properties due to the oral environment conditions. A series of biological responses on cells and tissues can be elicited by the leachable, potentially toxic agents due to acrylic based resins biodegradation. Oral microbes and mastication may be responsible for biodegradation processes (14,15).

Biodegradation of acrylic based resin may be due to saliva that is the product of small and large salivary glands. Water is one of the main factors to cause biodegradation in addition to be the most abundant component of saliva. When the water molecules penetrate the polymer network, it does allowing the diffusion of unbound or uncured monomers or additives from the material network (16,17). The amount of water diffusion can be affected by few conditions. First, the time needed for saturation with water may be affected by the water diffusion coefficient of the material. Secondly, the amount water molecules being replaced influenced by the amount of the residual components that are released (17,18).

Hydrolysis and enzymatic reactions are two mechanisms where polymeric structures and dental materials are chemically degraded in aqueous solutions. Potentially harmful by products as well as a deterioration of the network properties can occur through the degradation of the polymers by the salivary enzymes. The extent of degradation can be determined by the composition of the monomers producing the network, particularly when enzymes are responsible. Esterification of methacrylates is promoted due to presence of esterases in saliva (19,20). Reduction in the surface hardness and wear resistance are the effect of enzyme degradation on mechanical properties.

Bacteria colonization cause some surface degradation due to interactions between oral microbes and the polymer dental materials (21). The microorganisms that cause caries, periodontal disease, and denture related stomatitis which are present intraorally only can survive in the mouth if they adhere to non-shedding oral surfaces and begin to form colonies (22). Accumulation of dental plaque occur following bacterial adhesion on hard dental surfaces. The process contribute by surface roughness and the surface free energy play. However, alterations on these may have influence over bacterial adhesion and retention (23). Different dental materials have varies Surface free energy. Free energy on hard intraoral surfaces can be reduced by a thin biofilm of the acquired salivary pellicle. Rough acrylic resin surfaces are significantly more disposed to bacterial accumulation and plaque formation as reported by several studies in comparison to smooth surfaces. Fatigue, which is caused by relatively weak repetitive loads such as ordinary, masticatory force can cause biodegradation of the materials in the oral cavity. Progressive degradation and crack initiation and growth occur due to continuous application of mechanical and environmental loads, resulting in catastrophic failure of the resins. During the material processing, pre-existing voids were introduced to further assist the process. Wear produced due to mastication that gives shear and compression forces on denture teeth (24).

Denture material biocompatibility may be affected due to leaching of the residual monomer. Local chemical irritation, sensibilization and pain, labial edema, mucosal inflammation or ulceration, oral diseases such as burning mouth syndrome and denture stomatitis may appear due to products of acrylic based resin biodegradation. Furthermore, there are evidences that residual monomers in the denture base can affect the surrounding tissues when continuously in contact with large part of oral mucosa (25,26).

Adverse Effects of Resin:

The ability of a material to perform with an appropriate host response in a specific application as defined by The Williams Dictionary can determine the success of a dental product. The material is said to be biocompatible when a material does not interfere, neither toxic, injurious nor immunological with the living tissue. More unreacted double bonds will be formed with a material that has low degree of conversion that is capable of causing a reaction in living tissue (11).

There are common adverse effects associated with the use of resin in the oral cavity. They are genotoxicity and estrogenic effect. Genotoxicity is a toxicity that is refer to chemical breakdown of biological tissue. It is the ability of the material to mutate or breaking down a deoxyribonucleic acid, DNA. It is considered as a carcinogen (27). In case of estrogenic effect, it causes similar effects of a sex hormone when few materials bind to estrogen receptors. They are known as xenoestrogen (28). For example, Bisphenol A that is known as xenoestrogen (29).

When manipulating acrylic resins, the vaporization of the MMA monomer may occur. This may causes harmful effects due to inhalation which are capable to irritate the lung tissues and can also affect the central nervous system (CNS) (30). A study which involved rats that were exposed to MMA vapors showed that there were histological manifestations clearly present such as edema, emphysema, and even collapse of the lungs (31). Therefore, it must be stressed that the dental technicians who manipulate acrylic resin demand to work in an environment or condition which is entirely ventilated so that harmful effects such as dyspnea, cough, and triggering of asthma could be minimized and ideally prevented. MMA can penetrate the skin and it is also suggested that the resin during mixing is not held with bare hands since direct neurotoxic effects may be created. Myelinated nerve functions can be affected if MMA is absorbed directly through the skin and may lead to neuropathy in both wearer and dental technicians (32).

Contact allergy is a condition that can be seen in the denture wearers which is due to delayed hypersensitivity reaction. The effects of self-cured acrylic resins is much more when compared to the heat-cured ones, however, it must be highlighted that the symptoms of burning mouth and/or soreness could be arose due to a variety of other factors that include ill-fitting dentures and poor oral hygiene. The presence of saliva in the oral cavity acts as essential defensive barrier by diluting the potential harmful antigens before their penetration into the oral mucosa. Due to the high vascular nature of the oral mucosa the effect of the penetrated irritants can be minimized. However, this will mostly depend on the concentration of the residual monomer (33).

The application of resin based relining materials is involved in the chairside relining procedure. They are usually hard and soft reliners and care should be practised during their application as the residual monomer is readily leached out immediately and could be the main reason of irritation to the oral mucosa. Thus, the immersion of auto-polymerized resins in water before insertion into the mouth of the patient is very much important (34).

Direct effects on the skin of dental technicians and students in the laboratories can be resulted due to the monomer used during manipulation of acrylic resins. These effects are generally dependent on the time of exposure and are mostly occupational. It must be remembered that the gloves worn for cross infection control does not affect contamination by the monomers. The monomer penetrates vinyl and latex gloves and could become the reason of irritation to the skin of clinicians and the technicians as well as wearer. Ingestion of MMA either by mistake or deliberately can also lead to systemic side effects which affect the gastrointestinal tract and may cause CNS effects such as sleepiness, dizziness, headaches, and blurred vision (35).

Adverse Reactions Clinical Signs:

The cytotoxicity of denture base acrylic resins is influenced by the polymer to monomer ratio. Based on the study done by Jorge et al (36), he observed that resin prepared with a high portion of polymer (5:3) produce significantly much less residual monomer in his investigation regarding the effect of polymer to monomer ration on residual monomer levels. As more monomer is added to the mixture, there will greater amount of residual monomer, and hence, more ability to create toxicity (37) as found by Kedjarune et al (38).

Most common clinical signs of adverse reactions are contact type dermatitis and burning. As observed in few dentists and lab technicians, monomer acts as haptens in a delayed hypersensitivity mechanism. As reported by Stevensons and Moody (39,40), allergic, eczematous, contact dermatitis of the hands and face of dentists, that makes monomer as the culprit.

Another common symptom claimed by denture wearers that is similar to an allergic reaction is a burning sensation either in the oral cavity or in the tongue. The symptoms resembling to those of burning mouth syndrome. The patients with this syndrome suffering from taste disorder, which is called as dysgeusia, or complains of bitter or metallic taste like in the mouth. It was in 1941 when the first case was reported. The situation is also known as stomatitis venenata (41,42,43,44).

Patch testing can be done to confine skin allergies to acrylates. In this test, several suspected allergens are particularly prepared and are applied to the patient’s back that is suspected acrylate allergy in the period of 48 hours. Redness and elevation of the skin are results of the test that can be observed at the individual test site by a dermatologist.

Recommendations for use:

Local and systemic side effects as well as the environment are both affected when involve denture base resins and other materials used in dentistry. Thus, users must be made aware that the condition may get worsen if not taken care seriously. Below are the suggestions so that the drawbacks of denture base resins can be reduced.

· The areas where denture base resin materials are being used are entirely ventilated so that effects arise due to vaporization of the residual monomer can be minimized.

· Use impermeable gloves along with the use of aprons and protective eyewear.

· Use tightly sealed containers to store the material.

· When there is exposure, the site must be thoroughly washed with water particularly when the contact has been made with the eye. Remove contact lenses immediately and washed thoroughly.

· In order to facilitate breathing, move to an area with fresh air and loosen up tight clothing to in case contact was made, and ventilation was not appropriate. Clean the area thoroughly using appropriate cleaning agents if there is a spill.

· Use proper curing techniques and the vacuum mixing.

· In case of any symptom appearing and if they persist, immediately seek medical advice.

Treatments:

There can be edematous tongue that is possible to obstruct the airway in case of adverse reaction of the oral cavity. When the adverse reaction visible or elicited following the use dental materials containing resin, the denture should be removed immediately and the patient is seated upright in order to prevent airway. Later, levocetrizine 0.5 mg is administered. Otherwise, intramuscular dexamethasone 5 mg can be given followed by 500 mg amoxicillin for every 8 hours given after 2 hours. Next, intramuscular dexamethasone should be continued for 3 days and regular monitoring of patient should be performed.

DISCUSSION:

In dentistry, the contact allergy is a type of delayed hypersensitivity reaction in which a lesion of the skin or mucosa happens at a localized after multiple contact or exposure. There could be burning sensation of tongue, inflamed and edematous mucosa that is associated by severe burning. On the hands, it begins with transient vesicles, then rupture to form erosions and ulcerations that are much painful. The characteristics of allergic manifestations are erythema, papules, and edema and weeping blisters may appear in severe cases. Monomer presenting conventional heat cure acrylic resins is the main reason contribute to the presence of these allergic reactions. Haptens are formed when the antigens come in contact with the epithelial cells which later binds to Langerhan cells to the regional lymph nodes and present to the antigen to T-lymphocytes and hence the process of inflammation followed. In order to reduce the residual monomer, the post polymerized denture is soak in water bath with 55⁰C for one hour.

In a study conducted by Malmio University Hospital in Sweden, more than 1600 participants among dental staff and patients who has undergone patch test for allergy of dental acrylates, almost 50 of them had positive results to one or more acrylates. The highest recorded was 2-hydroxyethylmethacrylate followed by ethylene glycol dimethacrylate, triethylene glycol dimethacrylate, and MMA. In addition, as we keep it in higher temperature, as mentioned by Anthony Goon (44), the capacity of the allergen is much less. The mucosa may be severely irritated if there is direct application of relining materials. In order to avoid the allergy reaction, there are several low allergen free denture materials can be used. Rattner in 1936 was reported the first case of stomatitis venenata associated with plastic dentures wearer. Allergic reaction upon contact with skin and mucosa can occur with the presence of the liquid monomer of methylacrylate as found by Fischer in 1954. There are about 0.2 to 1% residual monomer in heat cure denture bases in comparison with autopolymerizing resins, which contain about 5% more (45) as demonstrated by Smith and Bains (46).

CONCLUSION:

Acrylic based resins are frequently used in dentistry practice as denture based materials, liners, restorative as well as orthodontic appliances materials. These products can be produced by polymerization of methacrylate related monomers. Despite of those benefits that the acrylic resin provided, increasing concern arises related to clinical application safety due to methods and conditions of polymerization reaction and the biodegradation under the oral surroundings. Cytotoxic effects of denture base acrylic resins can be related to the ratio of powder to liquid, the period for storage, method used for polymerization and the cycle when the methods and the conditions of polymerization are concerned.

Biodegradation occur may due to several factors such as saliva characteristics, mastication and oral microbes. Release of potential cytotoxic compounds from the polymer network result in adverse effects from the polymerization process and material biodegradation. Various adverse effects may appear on oral health including irritation, inflammation, and an allergic response of the oral cavity. Thus, more future research in various areas regarding the evaluation of acrylic based resins polymerization and biodegradation could be done to further concise definition of biocompatibility issues related to these dental materials.

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Received on 12.08.2018 Modified on 11.09.2018

Research J. Pharm. and Tech. 2019; 12(3): 1397-1402.

DOI: 10.5958/0974-360X.2019.00233.6