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<title xml:lang="en">Allergic effects of the residual monomer used in denture base acrylic resins</title>
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<name sortKey="Rashid, Haroon" sort="Rashid, Haroon" uniqKey="Rashid H" first="Haroon" last="Rashid">Haroon Rashid</name>
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<nlm:aff id="aff1">Department of Prosthodontics, College of Dentistry, Ziauddin University, Karachi, Pakistan</nlm:aff>
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<name sortKey="Sheikh, Zeeshan" sort="Sheikh, Zeeshan" uniqKey="Sheikh Z" first="Zeeshan" last="Sheikh">Zeeshan Sheikh</name>
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<nlm:aff id="aff2">Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Ontario, Canada</nlm:aff>
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<name sortKey="Vohra, Fahim" sort="Vohra, Fahim" uniqKey="Vohra F" first="Fahim" last="Vohra">Fahim Vohra</name>
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<nlm:aff id="aff3">Department of Prosthodontics, College of Dentistry, King Saud University, Riyadh, Saudi Arabia</nlm:aff>
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<idno type="pmid">26929705</idno>
<idno type="pmc">4745248</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745248</idno>
<idno type="RBID">PMC:4745248</idno>
<idno type="doi">10.4103/1305-7456.172621</idno>
<date when="2015">2015</date>
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<title xml:lang="en" level="a" type="main">Allergic effects of the residual monomer used in denture base acrylic resins</title>
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<name sortKey="Rashid, Haroon" sort="Rashid, Haroon" uniqKey="Rashid H" first="Haroon" last="Rashid">Haroon Rashid</name>
<affiliation>
<nlm:aff id="aff1">Department of Prosthodontics, College of Dentistry, Ziauddin University, Karachi, Pakistan</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Sheikh, Zeeshan" sort="Sheikh, Zeeshan" uniqKey="Sheikh Z" first="Zeeshan" last="Sheikh">Zeeshan Sheikh</name>
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<nlm:aff id="aff2">Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Ontario, Canada</nlm:aff>
</affiliation>
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<author>
<name sortKey="Vohra, Fahim" sort="Vohra, Fahim" uniqKey="Vohra F" first="Fahim" last="Vohra">Fahim Vohra</name>
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<nlm:aff id="aff3">Department of Prosthodontics, College of Dentistry, King Saud University, Riyadh, Saudi Arabia</nlm:aff>
</affiliation>
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<title level="j">European Journal of Dentistry</title>
<idno type="ISSN">1305-7456</idno>
<idno type="eISSN">1305-7464</idno>
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<date when="2015">2015</date>
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<div type="abstract" xml:lang="en">
<p>Denture base resins are extensively used in dentistry for a variety of purposes. These materials can be classified as chemical, heat, light, and microwave polymerization materials depending upon the factor which starts the polymerization reaction. Their applications include use during denture base construction, relining existing dentures, and for fabrication of orthodontic removable appliances. There have been increased concerns regarding the safe clinical application of these materials as their biodegradation in the oral environment leads to harmful effects. Along with local side effects, the materials have certain occupational hazards, and numerous studies can be found in the literature mentioning those. The purpose of this article is to outline the cytotoxic consequences of denture base acrylic resins and clinical recommendations for their use.</p>
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</TEI>
<pmc article-type="review-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Eur J Dent</journal-id>
<journal-id journal-id-type="iso-abbrev">Eur J Dent</journal-id>
<journal-id journal-id-type="publisher-id">EJD</journal-id>
<journal-title-group>
<journal-title>European Journal of Dentistry</journal-title>
</journal-title-group>
<issn pub-type="ppub">1305-7456</issn>
<issn pub-type="epub">1305-7464</issn>
<publisher>
<publisher-name>Medknow Publications & Media Pvt Ltd</publisher-name>
<publisher-loc>India</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">26929705</article-id>
<article-id pub-id-type="pmc">4745248</article-id>
<article-id pub-id-type="publisher-id">EJD-9-614</article-id>
<article-id pub-id-type="doi">10.4103/1305-7456.172621</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Review Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Allergic effects of the residual monomer used in denture base acrylic resins</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Rashid</surname>
<given-names>Haroon</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="corresp" rid="cor1"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sheikh</surname>
<given-names>Zeeshan</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Vohra</surname>
<given-names>Fahim</given-names>
</name>
<xref ref-type="aff" rid="aff3">3</xref>
</contrib>
</contrib-group>
<aff id="aff1">
<label>1</label>
Department of Prosthodontics, College of Dentistry, Ziauddin University, Karachi, Pakistan</aff>
<aff id="aff2">
<label>2</label>
Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Ontario, Canada</aff>
<aff id="aff3">
<label>3</label>
Department of Prosthodontics, College of Dentistry, King Saud University, Riyadh, Saudi Arabia</aff>
<author-notes>
<corresp id="cor1">
<bold>Correspondence:</bold>
Dr. Haroon Rashid Email:
<email xlink:href="drh.rashid@hotmail.com">drh.rashid@hotmail.com</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub">
<season>Oct-Dec</season>
<year>2015</year>
</pub-date>
<volume>9</volume>
<issue>4</issue>
<fpage>614</fpage>
<lpage>619</lpage>
<permissions>
<copyright-statement>Copyright: © European Journal of Dentistry</copyright-statement>
<copyright-year>2015</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-sa/3.0">
<license-p>This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.</license-p>
</license>
</permissions>
<abstract>
<p>Denture base resins are extensively used in dentistry for a variety of purposes. These materials can be classified as chemical, heat, light, and microwave polymerization materials depending upon the factor which starts the polymerization reaction. Their applications include use during denture base construction, relining existing dentures, and for fabrication of orthodontic removable appliances. There have been increased concerns regarding the safe clinical application of these materials as their biodegradation in the oral environment leads to harmful effects. Along with local side effects, the materials have certain occupational hazards, and numerous studies can be found in the literature mentioning those. The purpose of this article is to outline the cytotoxic consequences of denture base acrylic resins and clinical recommendations for their use.</p>
</abstract>
<kwd-group>
<kwd>Denture base allergy</kwd>
<kwd>denture base resins</kwd>
<kwd>residual monomer</kwd>
</kwd-group>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec1-1">
<title>INTRODUCTION</title>
<p>The use of acrylic based resins in dentistry has become very frequent, and these materials offer properties and characteristics due to which they can be used for many purposes. Common uses of these materials include the fabrication of denture bases, orthodontic removable appliances, temporary crowns, and denture relining.[
<xref rid="ref1" ref-type="bibr">1</xref>
<xref rid="ref2" ref-type="bibr">2</xref>
<xref rid="ref3" ref-type="bibr">3</xref>
<xref rid="ref4" ref-type="bibr">4</xref>
] The acrylic resin bases are used for removable partial or complete dentures and also for implant supported removable dentures.[
<xref rid="ref5" ref-type="bibr">5</xref>
] Orthodontic appliances made up of acrylic resin serve many purposes including space maintenance and arch expansion.[
<xref rid="ref6" ref-type="bibr">6</xref>
] The use of acrylic temporary crowns is important during crown and bridge fabrication processes, and these provisional restorations are usually placed after tooth preparation using temporary luting cement.[
<xref rid="ref7" ref-type="bibr">7</xref>
] Acrylic based soft and the hard relining process is very useful in removable prosthodontics which helps in improving denture's retention, stability, and support.[
<xref rid="ref8" ref-type="bibr">8</xref>
] Soft reliners are also useful for recording neutral zone impressions of completely edentulous arches.[
<xref rid="ref9" ref-type="bibr">9</xref>
<xref rid="ref10" ref-type="bibr">10</xref>
] The use of acrylic resins for copings in restorative dentistry has also been described, however, this use in modern dentistry is not widely documented.[
<xref rid="ref11" ref-type="bibr">11</xref>
]</p>
<p>Undesirable effects caused by denture base resins have been widely documented in the literature.[
<xref rid="ref12" ref-type="bibr">12</xref>
<xref rid="ref13" ref-type="bibr">13</xref>
<xref rid="ref14" ref-type="bibr">14</xref>
<xref rid="ref15" ref-type="bibr">15</xref>
<xref rid="ref16" ref-type="bibr">16</xref>
] The most common and frequently reported a problem with the patients having allergic reactions to denture base acrylic resin is mouth soreness and burning sensation. Areas presenting with burning sensation include the palate, tongue, oral mucosa, and the oropharynx.[
<xref rid="ref17" ref-type="bibr">17</xref>
<xref rid="ref18" ref-type="bibr">18</xref>
] Allergic tests carried on the skin of patients has also confirmed that the denture base acrylic resin is responsible for allergic reactions.[
<xref rid="ref19" ref-type="bibr">19</xref>
<xref rid="ref20" ref-type="bibr">20</xref>
<xref rid="ref21" ref-type="bibr">21</xref>
] Thus, whenever a denture wearer presents with signs and symptoms outlined above, a possibility of allergic reaction must always be considered, and thorough investigation carried out to achieve an accurate diagnosis. For the immediate and delayed type of hypersensitivity reactions, patch testing, blood tests, or allergen specific IgE tests can be carried out.[
<xref rid="ref22" ref-type="bibr">22</xref>
<xref rid="ref23" ref-type="bibr">23</xref>
]</p>
<p>The cytotoxic effects caused by denture base acrylic resins are mainly caused by the substances leaching out from these resins. The main substance which is leached out by the process of diffusion from these materials is the unreacted residual monomer.[
<xref rid="ref24" ref-type="bibr">24</xref>
<xref rid="ref25" ref-type="bibr">25</xref>
<xref rid="ref26" ref-type="bibr">26</xref>
] Constant contact of saliva with the material cause's expansion of the openings present between the polymer chains causing the unreacted monomer to diffuse out. Thus, the substances which are leached out from the denture bases into the saliva are transferred to the oral structures causing adverse allergic reactions.[
<xref rid="ref3" ref-type="bibr">3</xref>
<xref rid="ref27" ref-type="bibr">27</xref>
<xref rid="ref28" ref-type="bibr">28</xref>
]</p>
<p>It is worth emphasizing that steps must be undertaken to ensure that dental practitioners and students are aware of these adverse effects. The purpose of the current article is to outline the cytotoxic consequences of denture base acrylic resin, clinical recommendations for their use and to review previous similar published literature.</p>
</sec>
<sec id="sec1-2">
<title>CLASSIFICATION OF DENTURE BASE RESINS</title>
<p>Acrylic denture base polymers are mainly used for the construction of denture bases in partially or completely edentulous arches. A denture base is that portion of a denture which rests over the soft tissues in the oral cavity. McCabe and Walls[
<xref rid="ref29" ref-type="bibr">29</xref>
] classified denture base polymers into five types.
<xref ref-type="table" rid="T1">Table 1</xref>
outlines the classification of denture base polymers.
<xref ref-type="table" rid="T2">Table 2</xref>
outlines the main constituents of powder and liquid of denture base polymers where activator (N N’-dimethyl-p-toluidine) being only present in self-sure/auto-polymerized denture base resins.</p>
<table-wrap id="T1" position="float">
<label>Table 1</label>
<caption>
<p>Classification of denture base polymers[
<xref rid="ref30" ref-type="bibr">30</xref>
]</p>
</caption>
<graphic xlink:href="EJD-9-614-g001"></graphic>
</table-wrap>
<table-wrap id="T2" position="float">
<label>Table 2</label>
<caption>
<p>Composition of acrylic denture base materials[
<xref rid="ref29" ref-type="bibr">29</xref>
]</p>
</caption>
<graphic xlink:href="EJD-9-614-g002"></graphic>
</table-wrap>
<p>It has been reported that self-cured/auto-polymerized acrylic resins leach out higher quantities of residual monomer than heat-cured denture base resins.[
<xref rid="ref29" ref-type="bibr">29</xref>
<xref rid="ref30" ref-type="bibr">30</xref>
<xref rid="ref31" ref-type="bibr">31</xref>
<xref rid="ref32" ref-type="bibr">32</xref>
] Baker
<italic>et al</italic>
.,[
<xref rid="ref33" ref-type="bibr">33</xref>
] during their investigation found greater quantities of methyl methacrylate (MMA) in saliva of the individuals who were wearing dentures made up of self-cured/auto-polymerized denture base resins. Kedjarune
<italic>et al</italic>
.,[
<xref rid="ref34" ref-type="bibr">34</xref>
] stated that the quantity of the residual monomer was actually dependent upon the method of polymerization and the powder liquid (P/L) ratio used during mixing of the material. They recommended that it must be ensured that the amount of residual monomer is reduced before insertion of the dentures and suggested that the practitioners recommend to their patients that newly made dentures are not to be worn overnight so as to avoid mucosal irritation caused due to leachable residual monomer molecules.</p>
</sec>
<sec id="sec1-3">
<title>POLYMERIZATION REACTION AND THE MONOMER CONTENT</title>
<p>The polymerization reaction in denture base resins is an addition reaction that involves the activation of the initiator. It is usually through heat polymerization (heat-curing), auto-polymerization (self-curing), and light polymerization.[
<xref rid="ref34" ref-type="bibr">34</xref>
<xref rid="ref35" ref-type="bibr">35</xref>
<xref rid="ref36" ref-type="bibr">36</xref>
<xref rid="ref37" ref-type="bibr">37</xref>
<xref rid="ref38" ref-type="bibr">38</xref>
] The polymerization reaction (the curing process) results in the conversion of MMA into poly-MMA during which the monomer molecules are converted into polymers. During this process, not all the monomer molecules are converted and thus, some unreacted residual monomers remain unpolymerized.[
<xref rid="ref29" ref-type="bibr">29</xref>
] The unreacted monomer may leach out into the saliva which actually causes the cytotoxic effects in the oral cavity.[
<xref rid="ref39" ref-type="bibr">39</xref>
<xref rid="ref40" ref-type="bibr">40</xref>
] The greater the quantity of the unreacted monomer, higher will be the deleterious effects.</p>
<p>One of the important factors that must be considered during manipulation of denture base resins is the P/L ratio of the materials. When Jorge
<italic>et al</italic>
.,[
<xref rid="ref41" ref-type="bibr">41</xref>
] carried out a study investigating the P/L ratios of these resins during manipulation, they found out that when resins were prepared in the laboratory using higher levels of the polymer (contained in the powder) content that is, to a ratio of 5:3, lower quantities of the residual monomer were found. Lesser the amount of residual monomer, lesser would be the cytotoxic effects.[
<xref rid="ref34" ref-type="bibr">34</xref>
]</p>
<p>The polymerization temperature is another factor that plays a vital role and is responsible for different degrees of cytotoxic effects. When polymerization time is extended, the amount of residual unreacted monomer is reduced significantly and thus, the chances of cytotoxic effects are reduced. It has been recommended that a 7 h incubation in water at 70°C followed by a 1-h incubation in water at 100°C causes the maximum conversion of the monomer.[
<xref rid="ref42" ref-type="bibr">42</xref>
] It has been recommended that boiling during polymerization stage should be carried out for at least 30 min at maximum temperatures and that the heat-cured denture bases should be stored in water for 1–2 days before being delivered to the patients. This is expected to reduce the cytotoxic effects caused due to residual monomer to a significant extent.[
<xref rid="ref40" ref-type="bibr">40</xref>
] Self-cured denture bases which are additionally polymerized in water at 60°C and are kept in water at room temperature for a period of 1-day show significantly decreased amounts of residual monomer content.[
<xref rid="ref2" ref-type="bibr">2</xref>
]</p>
<p>Among various laboratory methods used to carry out polymerization of denture base acrylic resins, it is well understood that heat-cured acrylic resins have shown to produce less cytotoxic effects,[
<xref rid="ref43" ref-type="bibr">43</xref>
] while the greatest deleterious effects have been shown to be produced by self-cured acrylics.[
<xref rid="ref44" ref-type="bibr">44</xref>
] When cytotoxic effects of microwave cured acrylic resins were tested, it was shown that 20 min of polymerization carried out using microwave irradiation resulted in residual monomer content which was significantly reduced as compared to the monomer content found using other polymerization methods.[
<xref rid="ref45" ref-type="bibr">45</xref>
<xref rid="ref46" ref-type="bibr">46</xref>
] This reduction in the monomer content after using the microwave method of polymerization could play a vital role in the reduction of the hazardous effects of the material.[
<xref rid="ref47" ref-type="bibr">47</xref>
]</p>
<p>Optimum polymerization conditions must be identified and extended time for polymerization must be used to reduce the cytotoxic effects. Dentures fabricated using self-cured acrylic resins should be avoided, and immersion of newly made dentures in water should be recommended. However, regardless of the curing conditions, the unreacted residual monomer in denture base acrylic resins is inevitable and could be a source of the problem for both clinicians and the patients.[
<xref rid="ref48" ref-type="bibr">48</xref>
<xref rid="ref49" ref-type="bibr">49</xref>
]</p>
</sec>
<sec id="sec1-4">
<title>THE HARMFUL EFFECTS</title>
<p>Reports of allergic effects caused among professionals due to the use of dental materials are becoming increasingly common and patch testing has proven to be a reliable and easy way to detect these potential reactions.[
<xref rid="ref19" ref-type="bibr">19</xref>
] Clinical practice in prosthodontics involves the fabrication of implant-supported dentures, conventional fixed and removable partial dentures. Since the acrylic resin is the main constituent of these prostheses, allergic reactions may also be encountered in patients. As mentioned previously, unreacted MMA monomer may leach out into the oral cavity, and results in toxic effects and allergic reactions, especially, if the prosthesis is undercured. Significant damage at the cellular level involving cell membrane, mitochondria, and lymphocytes has previously been reported in the literature.[
<xref rid="ref50" ref-type="bibr">50</xref>
<xref rid="ref51" ref-type="bibr">51</xref>
]</p>
<p>During manipulation of acrylic resins, vaporization of the MMA monomer occurs, and this may causes harmful effects due to inhalation which can potentially irritate the lung tissues and can also affect the central nervous system (CNS).[
<xref rid="ref52" ref-type="bibr">52</xref>
] A study which involved exposing rats to MMA vapors showed that there were histological manifestations clearly present such as edema, emphysema, and even collapse of the lungs.[
<xref rid="ref53" ref-type="bibr">53</xref>
] Therefore, it must be stressed that the dental technicians who manipulate acrylic resin must work in an environment which is thoroughly ventilated so that harmful effects including dyspnea, cough, and triggering of asthma could be minimized and ideally avoided.[
<xref rid="ref54" ref-type="bibr">54</xref>
<xref rid="ref55" ref-type="bibr">55</xref>
] MMA can also penetrate the skin and it is also recommended that the resin during mixing is not held with bare hands since direct neurotoxic effects may be caused. Myelinated nerve functions have shown to be affected if MMA is absorbed directly via the skin and may lead to neuropathy.[
<xref rid="ref56" ref-type="bibr">56</xref>
]</p>
<p>Contact allergy is a condition seen in the denture wearers which is a result of delayed hypersensitivity reaction. As mentioned previously, the effects of self-cured acrylic resins is more as compared to the heat-cured ones, however, it must be stressed that the symptoms of burning mouth and/or soreness could be occurring due to a variety of other factors including ill-fitting dentures and poor oral hygiene.[
<xref rid="ref57" ref-type="bibr">57</xref>
<xref rid="ref58" ref-type="bibr">58</xref>
<xref rid="ref59" ref-type="bibr">59</xref>
] The presence of saliva in the oral cavity provides the essential defensive barrier by diluting the potential harmful antigens before their penetration into the oral mucosa. The effect of the penetrated irritants is also reduced due to the high vascular nature of the oral mucosa. However, this will largely depend on the concentration of the residual monomer.[
<xref rid="ref33" ref-type="bibr">33</xref>
<xref rid="ref34" ref-type="bibr">34</xref>
<xref rid="ref60" ref-type="bibr">60</xref>
<xref rid="ref61" ref-type="bibr">61</xref>
] The chairside relining procedure involves the application of resin based relining materials. They are usually hard and soft reliners and care should be exercised during their use as the residual monomer is readily leached out immediately and could be a source of irritation to the oral mucosa. The immersion of auto-polymerized resins in water before insertion into the patient's mouth is particularly important.[
<xref rid="ref43" ref-type="bibr">43</xref>
<xref rid="ref44" ref-type="bibr">44</xref>
]</p>
<p>The monomer used during manipulation of acrylic resins may cause direct effects on the skin of dental technicians and students in the laboratories. These effects are usually dependent on the time of exposure and are mostly occupational.[
<xref rid="ref62" ref-type="bibr">62</xref>
] It must be mentioned that the gloves worn for cross infection control have no effect over contamination by the monomers. The monomer penetrates vinyl and latex gloves and could become a source of irritation to the skin of clinicians and the technicians.[
<xref rid="ref63" ref-type="bibr">63</xref>
] Ingestion of MMA (by mistake or deliberately) may also lead to systemic side effects affecting the gastrointestinal tract and may cause CNS effects that is, sleepiness, dizziness, headaches, and blurred vision.[
<xref rid="ref64" ref-type="bibr">64</xref>
<xref rid="ref65" ref-type="bibr">65</xref>
]</p>
</sec>
<sec id="sec1-5">
<title>RECOMMENDATIONS FOR USE</title>
<p>Users must be made aware that denture base resins and other materials used in dentistry not only effect the environment but may also cause local and systemic side effects. The authors would like to recommend the following measures so that the deleterious effects of denture base resins can be minimized:</p>
<p>
<list list-type="simple">
<list-item>
<label>a)</label>
<p>It is highly recommended that the areas where denture base resin materials are being used are thoroughly ventilated so that effects caused due to vaporization of the residual monomer could be reduced</p>
</list-item>
<list-item>
<label>b)</label>
<p>The use of impermeable gloves is recommended along with the use of aprons and protective eyewear</p>
</list-item>
<list-item>
<label>c)</label>
<p>The material must be stored in tightly sealed containers</p>
</list-item>
<list-item>
<label>d)</label>
<p>In case of exposure, the site must be thoroughly washed with water especially if the contact has been made with the eye. Contact lenses should be removed immediately and washed thoroughly</p>
</list-item>
<list-item>
<label>e)</label>
<p>Move to an area with fresh air and loosen up tight clothing to facilitate breathing in case contact was made, and ventilation was not appropriate. If there is a spill, clean the area thoroughly using appropriate cleaning agents</p>
</list-item>
<list-item>
<label>f)</label>
<p>Proper curing techniques must be applied, and the use of vacuum mixing is recommended</p>
</list-item>
<list-item>
<label>g)</label>
<p>In case of any symptom appearing and if they persist, immediately seek medical advice.</p>
</list-item>
</list>
</p>
</sec>
<sec sec-type="conclusion" id="sec1-6">
<title>CONCLUSION</title>
<p>Whenever, a patient wearing an acrylic prosthesis complains for allergic reaction or chemical irritation, the possibility of these symptoms caused by denture base materials must be considered. These materials have good properties and offer reasonable esthetics, however; they may cause toxic side effects in some individuals. Regardless of the curing technique used, the presence of unreacted residual monomer in denture base acrylic resins is inevitable and could be a source of problem for both clinicians and the patients and techniques must be applied in laboratory and clinical settings to reduce the exposure as much as possible. In addition, emphasis must be given to raise awareness among the dental students and technicians about the possible hazardous side effects caused by these materials.</p>
<sec id="sec2-1">
<title>Financial support and sponsorship</title>
<p>Nil.</p>
</sec>
<sec id="sec2-2">
<title>Conflicts of interest</title>
<p>There are no conflicts of interest.</p>
</sec>
</sec>
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