Are Use Of Orthodontic Adhesives Detrimental To Health? An Overview.

INTRODUCTION

           Composite resins have been the material of choice for bonding orthodontic attachments to enamel since the 1970's. Composites are defined as a 3-D combination of at least two chemical materials with an interface that separates them. The resinous polymeric matrix consists of a system of monomers and initiators for polymerization and the inorganic part consists of glass, quartz, silica and the bonding agent that unites the inorganic particles with the resinous matrix.

           Since 1950's, it was declared that the biggest drawback of these chemically cured methacrylate systems was increased discolouration, recurrent tooth decay and pulp reactions due to polymerization shrinkage and monomer leaching¹. This may be due to increased bulk porosity while mixing the base and catalyst paste, thereby leading to increased bulk inhibition of polymerization and increased extent of oxygen inhibition due to the prolonged setting reaction ² .

           In 1956, Bowen introduced epoxy resins (diglycidyl ether of bisphenol A) and mixed it with silica filler particles to reduce polymerization shrinkage and increase strength. To overcome the inhibition of polymerization occurring in the epoxy resins when exposed to moisture , he attached methyl methacrylate groups to the end groups thereby converting the epoxy resin to a dimethacrylate – which lead to introduction of a new resin called Bis- GMA ie Bisphenol A glycidyl methacrylate (Bowen's resin).

Advantages of Bis- GMA

• Long rigid molecules with reactive double carbon bonds at both extremities.
• Reduced shrinkage during polymerization.
• Ability to form strong cross links

Disadvantages

• High viscosity
• Difficult to add filler to the monomer
• Difficulty in mixing the composites

           To solve this problem monomers of lower viscosities eg:-TEGDMA(trimethylene glycol dimethacrylate) were added to it. Inspite of all advances, current technology still does not allow a complete degree of conversion of monomers to polymers; thereby leading to residual monomer leaching from the resin intra orally.

           Recent studies have emphasized the potency of monomers leaching from the intra oral dental adhesives in causing cytotoxicity, estrogenecity , mutagenecity, inflammation and decrease in fertility. Leaching from a resin can occur at two stages; one during the setting period of the resin and one when the resin is degraded in the oral environment.

           Chemical, enzymatic and mechanical factors in the oral cavity also result in a low and persistent degradation of composites which could contribute to cytotoxicity and estrogenecity³. When a combination of different monomers are leached, it seems to be more detrimental than a single monomer species. Materials being leached from the composite include methacrylic acid, fillers, derivatives from enzymatic hydrolysis, benzoic acid resulting from degradation of benzoyl peroxide initiators and non- characterized substances². 0xidation of the pendant C-C double bonds can cause network degradation and release of formaldehyde upto.1-.5μL/cm³ which could lead to biocompatibility problems⁴. The content of BPA in unpolymerized composite resins has been reported to be in the range of 1.5-10.2μg/gm of resin² . A spectrometer or high performance liquid chromatography(HPCL) is the best method to study residual monomer content and degree of conversion .Depending upon which among the three types of manufacturing processes of Bis GMA is followed, the elutants can vary, if stringent product control measures are not followed¹.

Mutagenecity Of Composites

Mutagenecity (genotoxicity) can be defined as the ability to produce mutation in genes by causing specific DNA damage or chromosomal aberration . It was found that Gluma 3 exhibited mutagenicity in a dose-response manner ⁵. Mutagenic effects are known to cause serious diseases including carcinoma and birth defects.

Biocompatibility And Cytotoxicity

Biocompatibility may be defined as the ability of a material to function in a specific application in the presence of an appropriate host response⁶. This can be assessed by testing the toxicity of a material using either in vitro tests to study cytotoxicity or genotoxicity or by clinical studies in humans. Neutral red uptake is a fast, valid and reproducible method to evaluate cytotoxicity in vitro. Others methods include MTT colorimetric assay , DNA synthesis and lactate dehydrogenase activity.

           A study reported that Scotchbond I showed a cytotoxicity of 80% whereas all others showed a cytotoxicity of 50%⁷. Another showed that the activator components of the “no-mix” adhesives had the highest toxicity causing 100% cell death. They also found that One-to-one and Adaptic continued to cause cell death at both 30 days and 2 years post polymerization ⁸.

Effect On Male Fertility

Bisphenol A has been implicated in human infertility, genital tract malformation and increased cancer rates in estrogen sensitive target tissues. Laboratory tests on murines have shown an increase in prostrate gland weight at 6 months of age after in utero exposure to low dose levels and also reduced sperm efficiency and count . The fertility rate was reduced in females impregnated by BPA exposed male. The decrease in sperm count may be due to the direct effect of BPA on testicular Leydig and Sertoli cells causing a decrease in testosterone production by inhibiting the testicular calcium ATPase ⁹.

Estrogenecity

           Estrogenecity refers to the ability of certain substances in very low concentrations to be able to regulate differentiation and growth of selected tissues distant from the site of secretion.. Dodds and Lawson in 1936 reported estrogenic effects in some diphenyl compounds that contain two hydroxy groups in para position. One such derivative bearing two methyl groups is Bisphenol A, which is a component of BIS- GMA, a widely used composite resin. However if the Bisphenol A present in Bis- GMA molecule is sterically hindered and if the monomer is pure without any impurity , it cannot cause an estrogenic effect.

           The principle histological activity of estrogen in women includes development of secondary sexual characteristics, stimulation of uterine growth, control of pulsatile release of luteinizing hormone, thickening of vaginal mucosa and ductal development of the breast. In men, it may be involved in regulation of androgen and estrogen levels as well as sexual behaviour^1. Stomatic influence of estrogen can be manifested as increased severity of gingivitis, increased gingival probing depth and increased bleeding on brushing, gingival overgrowth and increased crevicular fluid production during pregnancy.

           It is however important to understand that not all chemicals with a phenolic A ring of cyclopentanoper hydrophenanthrene structure can be estrogenic.This potential depends on a number of factors like the delivery of unbound /free drug in proper concentration, binding and activation of receptor as well as the amount of time the free drug spends at the site of action1.According to Krishnan A.V, Bisphenol A was capable of increasing the number of cells and the progesterone receptor content of breast cancer cells but at 2500 times the concentration necessary for estradiol to produce similar effects ¹⁰.Recent data also shows that Bisphenol A is a weak agonist for both ERα and ERβ receptors.

Gingival Inflammation

It has been reported that Orthodontic adhesives induce human gingival fibroblast toxicity and inflammation., A study used a reverse transcription polymerase chain reaction and reported that adhesive contact on fibroblasts increased COX 2 m-RNA expression and prostaglandin E2 release; thereby causing inflammation¹¹.

Do We Really Need To Worry About Using Adhesives?

           The potential release of Bisphenol A from sealants varies according to the amount of time and type of medium in which it exists. When BISGMA was injected subcutaneously at doses higher than those monitored in saliva, it was unable to stimulate increase in cell number or cell size of reproductive organs in males, but stimulated a modest increase in weight and collagen content of uterus . Intra orally releasedglycidyl ether of Bisphenol A from BIS-GMA resins is poorly absorbed from the GI tract. Though BIS-GMA is lipophilic and can be transported from the intestinal tract to the site of action, this depends on a number of factors, including capillary permeability, blood flow, extent of plasma protein and specific organ binding, regional pH differences, transport mechanism and permeability of specific tissue membranes which are also unknown.¹

           The estrogenic effect observed in mice injected with commercial BIS-GMA may be a result of impurities ( Bisphenol A and diglycidyl ether of Bisphenol A ) or the biodegradation of BISGMA to Bisphenol A. Subcutaneous implant studies suggest that cured BIS-GMA containing materials are not toxic, which may indicate that biodegradation is limited. It was found by Munksgaard and Freund that of all resins, BISGMA released the least methacrylic acid when subjected to hydrolysis by porcine liver esterase. This may be due to the steric hinderance owing to the hydroxyl group in BIS-GMA that makes it more difficult for esterase to attack this molecule. It was also found that Bisphenol A can be released by an attack of esterase on BIS- DMA and not on BISGMA . Estrogenic effect of newly placed resins also showed a decrease over time¹ . The threshold for long term exposure of BPA is .05 mg/kg of body weight daily. Nathanson reported that .0001 μgms of BPA /gm of sealant is released in vitro.¹²

A Simple Test To Measure Monomer Leaching:

Matasa in 2000 used color changes in a potassium permanganate solution when a polymer was added to reveal the amount of monomer leaching¹³.In the presence of a polymer ,KMNO4 changes from purple to a yellow brown due to the precipitation of MNO2 and MNO3.If more polymer was added the colour changes to clear due to the formation of salt.

Precautions To Reduce Potential Hazards Of Monomer

• Care should be taken to remove the excess adhesive after polymerization, by washing the tooth with water spray.
• Care to be taken in areas where adhesives will be in intimate contact with the oral tissues – sub gingival and inter proximal.
• Only limited amount of material should be used for bonding.
• Complete evacuation should be accomplished with water spray and high speed suction.
• Light curing around the bracket edge (indirect) to be followed rather than through the brackets because bracket base thickness interferes with complete polymerization. ²
• Use of LED instead of halogen light to ensure greater degree of conversion of monomer, even at lesser irradiation time.¹⁴
• Place the light cure tip as close as possible to the tooth ,as increasing the distance decreases the degree of conversion of monomers and thereby increases BPA release.¹⁵
• Consider additional irradiation in areas with difficult access eg..rotated or malposed teeth.¹⁵

CONCLUSION

           Based on existing research, we must accept that certain impurities may be present in BISGMA based resins, which if released could have estrogenic and cytotoxic effects. However, the amount of Bisphenol A that may be present as an impurity or as a degradation product is quite small and far below the doses required to affect the reproductive tract or cause major cell damage in any organ. The release of Bisphenol A does not necessarily translate to any direct toxic effects on patients nor does it indicate any potential long term toxic effects. Further standardized tests are warranted to detect the Bisphenol A content of resins and their ability to release Bisphenol A when in use intra orally and its effects on the various tissues and organs of the human body. Formulation of benzene ring -free, high molecular weight monomers in future will eliminate concerns regarding intra oral use of BIS- GMA.