ANUPRABHA SHRIVASTAVA PG- 37 YR DEPT OF CONSERVATIVE DENTISTRY & ENDODONTICSCONTENTS ® Introduction ® Definition ™ Requirements of dental materials ® Tests for evaluation of biocompatibility ® Allergic responses to dental materials ® Standards that regulate the measurement of biocompatibility * Biocompatibility of dental materials = Reaction of other oral soft tissues to restorative materials = Reaction of bone & soft tissues to implant materials = References = ConclusionINTRODUCTION © Biocompatibility refers to the study of interaction of various materials with human tissues. © Materials used in dentistry come into direct contact with the hard tissues of the teeth, the oral mucosa, the pulp & the periapical tissues. © Due to this intimate, long term contact, the materials should exhibit a high degree of biocompatibility. © For the biocompatibility of a biomaterial it is not only important that minimal diffusible substances are released when it is in body contact, but the material must also solve the purpose for which it has been designed. ~© Biocompatibility of dental materialsis characterized by many parameters such as: Mutagenicity of the material to an appropriate biological aR eeN tact) le-Velelan Ameo LeeOTHER DEFINITIONS COMPATIBILITY: (To compath- to sympathize with) © Astate in which two things are able to exist or occur together without problems or conflict. BIOMATERIAL: © A synthetic material used to replace part of a living system or to function in living tissue.BIOCOMPATIBILITY REQUIREMENTS 1. They should not sensitize & produce allergic reactions. 2. They should not undergo biodegradations. 3. They should not be carcinogenic. 4. They should not contain any toxic diffusible substances which get released & enter into the circulatory system. 5. They should not be harmful to soft & hard tissues of the oral cavity in particular & the whole body in generala HOW BIOCOMPATIBILITY IS RELEVANT TO DENTIST© Dentists potential concern about biocompatibility can be organized into 4 areas: Legal ie. Safety of the liability ; patient Regulatory Safety of compliance the dental issue out staffSAFETY OF THE PATIENT: Evidence has shown that, although adverse reactions to dental materials are| not common, but still they can happen. These adverse events occurred locally & systemically. © It is therefore every practitioner's responsibility to access the risk of dental materials, taking into account each patient's unique history.2. SAFETY OF THE DENTAL STAFF: © The staff may be chronically exposed to materials when they are being manipulated. © The classic example of this problem is dental amalgam, because the release of mercury vapour from amalgam during placement or removal is substantially higher than when it is undisturbed in the mouth. © Dental staff are also at a risk from chronic contact with latex & resin based materials.3. REGULATORY COMPLIANCE ISSUE: © Biocompatibility issues are closely linked to regulations that affect dental practice. © Examples of this link are: a) Dental amalgam: Because of the biologic concerns about mercury, regulators have considered monitoring & restricting the amount of mercury in waste from dental practices. b) Another example is the use of latex.4. LEGAL LIABILITY: Because dental materials can affect the well being of patients & dental auxiliaries, practitioners assume a legal risk when using these materials. Litigation as a result of biomaterials causing harm to a patient is probably rare Nevertheless, when these problems occur, they are emotionally & financially stressful to the practitioner.BIOLOGICAL INTERFACE As the definition of biocompatibility suggests an interaction between the body & the material. © Placement of a material in the body creates an interface that is normally not present. This interface is not static, rather it is the site of many dynamic interactions between the material & the body through which the body may alter the material or the material may alter the body.© The activity of this interface depends on: + wu a 4. 4 types of interaction can take place: The location of material. Its duration in the body. The properties of the material. Health of the host. Between the material and oral cavity. Between the material and the pulp (Via the dentinal tubules) Between the material and periodontium. Between the material and the periapical bone.ADVERSE EFFECT OF DENTAL MATERIAL te TT toxicity y, ‘Cross reactive allergy * Concurrent Allergy Mutagenicity Carcinogenicity Genotoxicity Teratogenicity1. TOXICITY © Toxicity of a material describes the ability to damage a biological system by chemical means. © Dental materials may release certain substances which can cause toxicity. a. IMMUNOTOXICITY of a material describes adverse effects on the structure and function of the immune system. © — This may lead to: 1. Impaired host defence. 2. Tissue damage.b) SYSTEMIC TOXICITY © Here site of application & site of adversg@eactions are different. © Almost all dental materiasf e oral cavity, from where they may entgc) LOCAL TOXICITY * Substances released from dental materials may generate a reaction (e.g., inflammation or necrosis) in adjacent tissues such as oral mucosa/ gingiva, pulp or alyao * Howeve responsib 1. Bacte 2. Mechanical/physical irritation, such as pressure caused by dentures.( 2. INFLAMMATION © The inflammatory response is complex & it occurs to ward off some threat. ® Histologically, the inflammatory response is characterised by 1. Edema of the tissue. 2. Inflammatory cells infiltration such as neutrophills (in the short term) or monocytes and other lymphocytic cells (in the long term).g3- ALLERGY © Allergy is an abnormal - antibody reaction to a substance that is harmless to most individTypes |, I, and Ill are mediated by antibodies, whereas type IV is primarily imparted by cells. Dental materials may cause allergies of type | (immediate reaction) and ontact urtica exposure to latex proteins in disposable gloves. Delayed reaction : Allergic reaction to components of the root canal sealer AH26.ALLERGY CROSS- ALLERGY if ~~ CONCURRENT- ALLERGY Ifan individual is allergicto a Itis generated by 2 allergen particular element, then that are frequently present at itmay be assumed that he pallte: will also allergic to chemically time within a material or a similar environment. elements. e.g. — Ethlene glycol ' dimethacrylate (EGDMA) Hydroxyethyl Methacrylate (HEMA) Allergy to nickel, palladium, and cobalt was confirmed by patch testing J4. OTHER REACTIONS 1. Genotoxicity © Refers to the ability of substance released from materials to cause alterations of the genome DNA. 2. Mutagenicity © It is the ability of a substance to pass genetic damage on the next generation. e.g. — Ni, Cu and Be are known mutagens.3. Carcinogenicity: © It is the ability of a material or substance released from it to induce malignant tumors. 4. Teratogenicity: It is the ability of certain substance to cause malformation during embryonic development.1, LEVELS OF BIOCOMPATIBILITY GENERAL BIOCOMPATIBILITY: Determines the toxicity of the material at a cellular level. IMMUNOLOGICAL BIOCOMPATIBILITY: Determines of how an individual reacts to the material. Tests performed to determine the body's immunological response are: Clifford Materials Reactivity Test Kinesiologic testing When evaluating a Clifford test, a material that tests NS (not suitable) should not be used. On the other hand, materials that test S (suitable) should, ideally, be further tested.3. BIO-ENERGETIC BIOCOMPATIBILITY: © Using Electrodermal Screening (EDS) and Applied Kinesiology (AK or Muscle Testing), interaction between body & material is determined on an energitic level. © If energetically incompatible materials are used, interferences are created on the meridians associated with the teeth being restored.MEASURING THE BIOCOMPATIBILITY OF DENTAL MATERIALS © It is impossible to measure the biocompatibility of a dental material by any single test method. © The material needs to be evaluated by conducting a series of structured in vivo and in vitro test.i © Autian (1970) was the first to propose a structured approach in biocompatibility testing: 1. Non specific toxicity (Cell culture or small laboratory animals): ¢ These tests are carried out on models which do not simulate clinical situation. 2. Specific toxicity (Usage tests e.g. in subhuman primates):Theses | @ Tests are conducted on models which simulate the clinical situation. 3. Clinical testing in humans. ~© In 1984, it was Langeland who proposed a sequence which was later adopted as the ISO technical report 7405: (Cytotoxicity, Mutagenicity) aia ( Sensitization, ~~ Implantation tests, Mucosal irritation)© According to phillips there are three basic types of tests used to measure biocompatibility of dental materials:Oe id [Animals or Te] Initial Test / Primary i AYs [Invitro or Animals]© The initial tests (Phases | and II) are of a short duration, simple and cost effective. © Only after completing initial test, the material progresses through the testing hierarchy ie from simpler in vitro tests to the more complicated in vivo tests. © Usage test can be performed in animals or humans. © When humans are used, usage test is termed as clinical trial. Phase I and II Initial tests Phase IIT Animal usage tests Phase IV Clinical tests© The usage tests are more likely to be performed on large animals with anatomy that more closely resembles that of humans. © These usage tests are gold standard, in that they give the ultimate answer that whether a material is biocompatible or not.cuanmanaer| —_— —— TESTFOR 1, Pulp/ Dentin ) test | §) 2. The dermal toxicity _ 2. Pulp capping | ’ | and Pulpotomy Drea eT tests d 3 } 3. The inhalation toxicity | // usage tests Y | 3. Endodontic | tests / | Usage Test | f / | 4. Intraosseous | 3} Implant Test OCU SS utc permeability 1. Cell growth. l ee lj ie Tei tcule ra rodIN VITRO TESTS ( | Y Done in some biological system outside a living organism. Y The contact can be either: Direct Material is present between the AMM ALA ANAL ¥ Two types of cells can be used for in vitro tests. Primary cellsCYTOTOXICITY TESTS DEFINITION: © To cause toxic effects at the cellular level. DIRECT CONTACT TEST Time e);---~(®@ \ftk A material sample (S) is placed in the center of a cell will culture well, and cells and medium are added.After 1-3 days, the cells have multiplied in areas where the material has not inhibited their growth.The area devoid of the growth is often referred to as zone of inhibition. icMEMBRANE PERMEABILITY TESTS e Iti ne cr NR Healthy cell Injured cell (intact membrane) (permeable membrane) TB Healthy cell Injured cell (intact membrane) (permeable membrane) or very hey are mbrane. nup if an blueA, 2, 3 TESTS THAT USE BARRIERS [INDIRECT TESTS] Agar diffusion test/ tissue culture overlay test method Millipore filter assay Dentin barrier testsAgar Diffusion testing © Amonolayer © The cell stair en agar layer is placed overt! vated for 24 hrs. © Agar forms a © Ifthe test ma ‘e within cells as they lyses. © )a = Y Acellulose acetate filter having 0.45pm filter is used. Y Cells are grown on one side of the filter and the test material placed on the opposite side of filter. diffuse through the pores to exert a cytotoxic effect on the cells.® Dentin forms a barrier through which toxic materials must diffuse to reach the pulp. A Showing the material is placed on one side of the disk. ntin disk ire medium or saline) is on the otherMUTAGENESIS ASSAYS * It assess the effect of dental material on a cell’s genetic material: 1. Ames test: *It uses mutant stocks of Salmonella Typhimurium that require exogenous| histidine. Native stocks of bacteria do not require exogenous histidine. If the mutant stocks bacteria are treated with a mutagen there will be a mutation back to the normal state and growth in histidine free medium will occur. 2. Styles cell transformation test : Done in mammalian cell. L e~ ( TESTS FOR CELL METABOLISM OR CELL FUNCTION © Bio synthetic or enzymatic activity of cells are used to measure cytotoxicity of the test material. © Eg. Tests that measures DNA synthesis or protein synthesis 1, MTT test (3-(4,5 — dimethylthiazol — 2 — yl)-2-5-diphenyl tetrazolium bromide test 2. NBT (Nitroblue tetrazolium) 3. XTT (2.3- Bis-(2-methoxy- 4-nitro-5-sulfopheny)-2h- tetrazolium-5-carboxanilide salt) 4. WST (a Water —soluble tetrazolium)Test Advantages Disadvantages In Vitro test en aa ae Short duration Simple Cost effective Good control over experiment Large scale screening Can be standardize Relevance to in vivo is questionableIMPLANTATION TEST © Materials tested in this way are the ones that directly and periodontal therapy. © Amalgams and alloys are also tested because the marin fig cestoative materials conti e gingiva. SHORT TERM LONG TERM IMPLANTATION IMPLANTATION TEST. TEST Material is placed Material is placed for 1-11 weeks for 1- 2 yearsTHE DERMAL TOXICITY TESTS Y The test material is injected intradermally & skin hypersensitivity reactions are checked. ¥ For the main test, the highest concentration of the test material that causes no more than slight erthema and edema is selected. eTHE INHALATION TOXICITY TESTS *An aerosol of the test material is sprayed |p around the head of experimental animal in a chamber periodically. * If the animal dies in a few minutes, or hours, the materials are considered toxic. oeTest Advantages Disadvantages In Vivo test Allows complex systemic interactions. More relevant than in vitro tests. 1. Time consuming. 2. Expensive. 3. Legal ethical concerns.PULP / DENTIN TEST ® Class V cavities are prepared as atraumatically as possible and are then filled with the test material. ¥ Promising test materials induce the least inflammatory response in the pulp. Yifa response is produced, the time required to disappear is also measured.PULP CAPPING AND PULPOTOMY USAGE TESTS.) Vv Here, the testing produces are same except that the pulp is merely exposed for the pulp capping evaluation and is partially removed for the Pulpotomy assessment. VY Observations are made of dentinal bridge formation directly against the capping material. ENDODONTIC USAGE TEST VY Here the pulp is completely removed from the pulp chamber and root canals replaced by the obturating test material and control material.INTRAOSSEOUS IMPLANT TEST aa implant} Sd 0 Raa an) Ree ASC. Hina aL In ddan) 3 to7 years Ne S YNTest Advantages Disadvantages Relevance to use of material is} 1. Very expensive. assured. Usage test 2. Very time consuming. 3. Major legal _ ethical issues.TEST PROGRAMS FOR THE BIOLOGICAL TESTING OF DENTAL MATERIAL Test method describe the manner in which test are to be used. ‘The test programs that can be adopted are : a ¢ Non Linear Progression of tests RaLinear Progression of tests Progress of testing a Number of materials igure 1: Classical paradigm by AutianDisadvantages 1. Mjér et al. Demonstrated that the materials that cleared the first two tests were not entirely harmless at the clinical usage level. e.g. ZOE when tested in vitro completely kills every cell in the culture, but in clinical practice, the same cement has been successfully used for many years with no evidence of pulp damage. 2. It is time consuming since it is performed in a sequential manner.Non Linear Progression of tests * Mjor in 1977 he modified the linear paradigm to a non-linear pattern, where simultaneously all three tests would be performed on the tested material. 7S ISL] Figure 2: Revised paradigm by Mjor 2 £ g . 8 8 e aSTANDARDS THAT REGULATE THE MEASUREMENT OF BIOCOMPATIBILITY © The biocompatibility tests are standardization to make it more uniform within individual countries and around the world. ® The first biocompatibility test standard for dental materials was document number 41.ANSI/ADA Document 41- National standard This was approved by the Council on Scientific affairs in 1972 and was updated in 1982 to include tests for mutagenticty. This specification uses the linear paradigm for materi eaninc_and divides testing into initial, secondary, and usage tests Document No 41. is currently being revised , but the revision is not complete, so the 1982 version is still in force.ISO STANDARD 10993 © Itis the international Standards for testing the biocompatibility of dental materials. © Unlike ANSI/ADA Docume! e ISO 10993 standard is not restricted to dental materia © This document snodified versions are updated peg aa ; s is hn , ‘Some relevant parts that covers biological testing are given below ISO 10993 — 3: 1992 | Test for genotoxicity , carcinogenicity, [7s] DRAWBACKS OF STANDARDS |} Very time consuming. | | IS\ 2. All the latest advancements in testing ds |_| cannot be incorporated into existing || IS\ standards immediately. on IS\ ISO 10993 — 11; 1992 | Tests for systemic toxicityCOON eter) of Dental N ee Ua ——Silver Amalgam Elemental Mercury can lead to systemic toxicity. Systemic | It.can enter into human body through the skin, by ingestion, or by inhalation of mercury vapors. toxicity § Inhalation is the most common route of entry __| among patients and dental personnel.dental office: 1. Improper storage of mercury . The following are the sources of mercury exposure in the Systemic toxicity 2. Exposure during manipulation i.e trituration, insertion 3.__Exposure during finishing and polishing. ~ RETROGRADE DEGENERATION OF NEURITE GROWTH CONE INTHE PRESENCE OF 107 MOLAR MERCURY CHLORIDE. NOTE THE TRIANGLE REFERENCE MARK. ye < ; JLocal Toxicity Pulp Reactions: 1 2. 3. Oral Mucosa reac a ze Reduced number of odontoblast. Dilated capillaries. odontoblastic layer, An inflammi following the leep cavities. Gingivitis Bleeding gums — al or lingual mucosa ed by entry of dental amalgain into the softAllergic reaction Type 1V — Delayed allergic type reaction may be seen in the oral mucosa in contact with the restorations. Other reactions No evidence of mutagenic or carcinogenic reactions.* Amalgam contains free mercury was discovered & demonstrated by IAOMT member Roger Eichmann. * An extracted tooth containing an old amalgam filling is held in the light of a miner's blacklight, which is nothing sphors, [a pure mercury vapour discharge lamp]. * By the principles of atomi e only cold vapour that could absorb the wavelength of mi \dow would be that of mercury itself. * The filling was dipped in 110° F water, to simulate the type of mild heating one would expect from chewing, grinding the teeth, or drinking hot liquids. The smoke visibly emerging is the shadow of mercury vapour.DENTAL CASTING ALLOYS The number of elements released from the dental alloys is ; for e.g. the amount of zinc released Suse cond (aiyy¥ Casting alloys that .arein intimate contact with the gingiva will form a“ microenvironment”. YAn example of a“ microenvironment” is the gingival sulcus, ¥When there is a release of elements from the alloys, andif itis presentin more conc.*in the “Sulcus than in’saliva, then epithelial cells of the sulcus will more prone to Cytotoxicity. YAll casting alloys. release elements, but all elements are, not cytotoxic.Baer : Eulray Beet s-aclel a)¥ Through Ni ions by themselves are weak mutagens, Ni subsuflide is a documented carcinogen. Y The oxidative state of Cr determines its Mutagenicity. Cr3+ is not mutagen whereas Cr6+ is. ¥ Beryllium vapors created during casting and finishing of prostheses are mutagenic. ¥ Cadmium ions have been shown to be carcinogenic.CERAMICS Risk of silicosis among dental technicians due to inhalation of ceramic dust. Silicosis is a lung diseases characterized by shortness of breath, cough, fever, and cyanosis. Dust removal measures should be followed in the laboratory.Zirconium oxide ceramics show some amount of Other Reaction radioactivity due to contaminants such as thorium and uranium. However, the radioactivity level is not very significant.RESTORATIVE MATERIALS Tooth Coloured Cements——— "TOOTH COLOURED.CEMENTS [ \ ‘ \, ue Cements \ Tor i 2. Glass lonomer CementSILICATE CEMENTS © It have been used for many years as anterior filling material. © These material have been replaced more and more by adhesively applied resin based composite because it is classed as a severe irritant to the pulp. © Its pH at time of insertion is 2 & even after one month pH remains below 7.GLASS IONOMER CEMENTS Systemic toxicity | No evidence of systemic toxicity with conventional or resin modified glass ionomer cement (RMGIC). GICis oxic to the pulp. The cytotoxicity is attributed to the of the cement and release of ions. Local toxicity 2. De present between the pulp and the cement acts like a3. Dentin should be moist before the cement is placed in the prepared cavity. flrs ice ee If dentin is over dried, the cement will withdraw water needed for the setting reaction from the dentinal tubules, which will result in pain. 4. RMGIC is cytotoxic in the uncured stage butis only slightly cytotoxic after curing.Allergic reaction 1. Conventional GIC : No reported allergic reaction. Allergic skin reactions to methacrylate-based dental materials Other reactions No evidence of mutagenic or cariogenic reactions. @ )i TOOTH COLOURED RESINS 1. Unfilled resins 2. Resin Composite 3. Resin modified GIC 4. Polyacid Modified Composite Resins 5. Dentin Adhesives Beit & Fissure sealant( COMPOSITE RESIN &POLYACID MODIFIED COMPOSITE RESIN ~\ No evidence of toxicity. But, there is some concern regarding BPA (bisphenol A ), Systemic toxicity which can act like a Xenoestrogen. A Xenoestrogen is a compound that can mimic the effects of estrogen and cause reproductive anomalies. However, studies have shown that the xenoestrogenic potential of BPA used in dental composite is not very significant.~ ] V Ric = GMA_TEGDMA, and Methylmethacrylate (MMA) can act . individuals. Allergic Reaction a Type 1V delayed [primary risk tion. factor related ; to composite] nnel she ' dling these n , } ough a Hence, F | oves Swelling of upper lip due to TEGDMA BYTES ORM RLM LoR a to methylmethacrylate contactNON RESIN CEMENTS, LINERS & VARNISHES Calcium Hydroxide Varnishes Zinc Phosphate Cement Zinc oxide Eugenol Cement 1. 2. 3. 4. 5. Zinc Polycarboxylate cementCALCIUM HYDROXIDE 2 2 No reported systemic reai ion Pulp reaction Local toxici the pulp, produces superficial coagulation necrosis. Y This acts like a stimulus for the differentiation of secondary odontoblasts that lay down tertiary dentin. Direct pulp capping material: When in direct contact with if the pm.Allergic Reaction No reported allergic reaction ioe) idence of mutagenic or lOgenic reactionZINC PHOSPHATE CEMENTPLONE CUCL aL) To mere CeCe re) (2.552 ycesoy should always be done with: * Calcium hydroxide ** Cavity varnishAllergic Reaction No reported allergic reaction Other reaction No evidence of mutagenic or carcinogenic reactionSystemic toxicity | No reported systemic reaction Pulp-reaction as ae = reaction-when 4 The cementcan produce: applied to Local Toxicity the pulp. = 2=Hf there-is-a-cot 1 between: the-pulp-and-the-cement, == i will occur. —— = if OF ALL THE CEMENTS: pH ie. pulpal response] nese EugenoFhas the capability-to “transmission-of-= - of the nerves, hence, this cement has an: effect when used in deep cavities.response in some individuals.i ZINC POLYCARBOXYLATE CEMENT Systéniic toxicity, Local toxicity No reported systemic reaction: o . Pulp reaction 1. The pH of freshly mixed cement is 3 - 4. After 24 hours is 5 — 6. 2. Inspite of the acidic nature of the cement, it procedures minimal irritation to the pulp. The reasons for this are as follows: Y Liquid is more rapidly neutralized by the powder i, e its pH rises more rapidly than Zn phosphate. Y The polyacrylic acid molecule is larger in diameter than the dentinal tubules which limit its diffusion into the tubules.Other reaction No evidence of mutagenic or carcinogenic reactionfo ENDODONTIC MATERIALS>) ROOT CANAL SEALERS *There is no systemic toxicity is reported with most of the | Systemic | sealers. | toxicity | * However, paraformaldehyde containing sealers (N2) contained heavy metals such as lead and mercury. These metals | can transport to vital organs via blood & hence there use is discontinued. | 1. Para formaldehyde containing sealers: Severe cytotoxic Local response. toxicity They can irreversibly affect nerve conduction and result in paresthesia. 2. ZOE based sealers : Moderate cytotoxic response.(O >) 3. Resin.— based sealers: Cytotoxicity is less than that of para formaldehyde containing sealers. Local . ; 4. Ca Hydroxide based sealers: Less cytotoxic » than above mentioned sealers. Some amount of neural Toxicity, damage has been reported with these sealers.EP cat) 1) Paraformald Zn genol ZnoE eugenol bisphenol A Other ReactionseseSealerse CR COLL (delayed) to CIOL aLL NC) A LAM RCE SCLC XL EeeOBTURATING MATERIALS Vy bsg rn used earlieras obtur: noel etaley steng longer used due to their corrosion. potential.” ¥ Gutta — prtni only sigh ojo [in cell culture). © ¥ ee ¥, NOTE: For “thermoplasicized “guitapercha tae the recommended temperature while tising—techniques can result ‘/in damage to periodontal tissues.: Least cytotoxic of all dental material. The oytotoxicity is similar to the chemically inert titaniumLATEX MATERIALS T Systemic No systemic toxicity is reported with it. toxicity Allergi Reaction Contact urticaria (immediate, IgE-mediated aller reaction) following occupational exposure to latex proteins in disposable gloves 2. Type 1V delayed hypersensitivity reaction (Allergiccontact dermatitis)Allergic Reaction Other Reactions Y Type | reaction : Due to proteins present in natural latex v Type 1V: Due to accelerators and antioxidants used in latex manufacturing. Precaution to be taken are as follows: Non latex synthetic materials such as Nitrile and Styrene Ethylene Butadiene Styrene (SEBS) should be used. Polyethylene or Polyvinyl chloride rubber dams can be used instead of latex. No Mutagenic or carcinogenic effect is reported with latex rubberCONCLUSION @ It is mandatory for the clinician to know and understand the biocompatibility of the dental materials, so as to provide maximum advantage & minimum risk to the patient.REFERENCES Science of dental materials-Philips,10" edition Restorative dental materials-G.Craig & John M. Powers,11" edition. Notes on dental materials-Combe,5" edition. Gottfried Schmalz Dorthe Arenholt-Bindslev Biocompatibility of Dental Materials International web site: www.google.comTHANK YOU