Principles of biocompatibility for dental practitioners

John C. Wataha, DMD, PhDa School of Dentistry, Medical College of Georgia, Augusta, Ga.
This article is an evidence-based tutorial on the principles of biocompatibility. Although the technical issues of biocompatibility may seem beyond the scope of most practicing dentists, knowledge of these issues is fundamentally important to ensure the health of patients, dental staff members (including laboratory personnel), and practitioners themselves. Furthermore, the legal liability of dentists is often linked to biocompatibility issues. The biocompatibility of a material is not absolute; it must be measured with regard to the way the material is used. Measuring biocompatibility is a complex process that involves in vitro and in vivo tests. These tests contribute to understanding biologic responses to a material but cannot define the materials biocompatibility with 100% certainty. Practitioners should understand enough about biocompatibility testing methods to critically judge advertising claims and ask relevant questions of manufacturers. Because there is no infallible way to assess biologic response to a material, decisions about the clinical use of a material ultimately must weigh the biologic risks of a material against its potential benefits. (J Prosthet Dent 2001;86:203-9.)

he complexity and technical nature of biocompatibility issues may appear beyond the scope of practicing dentists. However, these issues have profound ethical, social, technical, and legal effects on prosthodontic practice. Because of the nature of prosthodontic therapies, dentists rely heavily on dental biomaterials. This reliance on materials makes biocompatibility issues especially relevant to prosthodontists and other restorative dentists. This article provides an overview of the biocompatibility principles that practicing dentists should understand. A definition of biocompatibility, its relevance to clinical practice, and an overview of how it is measured are presented.

WHAT IS BIOCOMPATIBILITY?
Given the importance of biocompatibility to prosthodontics and prosthodontic materials, it is surprising how few practitioners understand what biocompatibility really is. One widely accepted definition of biocompatibility is the ability of a material to elicit an appropriate biological response in a given application.1 If examined closely, this definition implies an interaction among a host, a material, and an expected function of the material (Fig. 1). All 3 factors must be in harmony before the material can be considered biocompatible. A discussion of 3 key concepts about this definition will reinforce this idea.

Fig. 1. Interactions between host, material, and application of material are important in biocompatibility. Biocompatibility exists only when all 3 factors are considered, and it can change if any of these factors change.

Biomaterials are not biologically inert

Practitioners should understand that there are no inert materials.2 When a material is placed into
Financial support provided by Metalor, Medical College of Georgia Biocompatibility Program. aProfessor, Department of Oral Rehabilitation. AUGUST 2001

living tissue, interactions with the complex biologic systems around it occur, and those interactions result in some sort of biologic response. The interactions depend on the material, the host, and the forces and conditions placed on the material (its function). Regardless, the material affects the host and the host affects the material. Inertness of materials implies an absence of such interactions. Most
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Fig. 2. Color of material depends on interaction of material with light and observers interpretation of affected light. Changes in light source, characteristics of material, or observer will change perceived color. Thus, color is property of material interacting with its environment. Biocompatibility is also property of material interacting with its environment.

scientists today agree that no material is truly inert in the body.2

Biocompatibility is a dynamic process

Biocompatibility is a dynamic, ongoing process, not a static one. A dental implant that is osseointegrated today may or may not be osseointegrated in the future. The response of the body to a material is dynamic because the body may change through disease or aging, the material may change through corrosion or fatigue, or the loads placed on the material may change through changes in the occlusion or diet. Any of these changes may alter the conditions that initially promoted an appropriate and desired biologic response. The interactions among material, host, and function continue over time; therefore, the biologic response to a material is an ongoing process.

the same situationsame host, same placement technique, same loadno osseointegration will occur. Conversely, if a titanium alloy is used as the ball portion of a femoral hip joint, it will wear against the acetabulum into small particles that ultimately will cause the hip to fail.4,5 Yet the cobalt-chromium alloy, which wears less, will do better. Because biocompatibility depends on the interaction of the material with its environment, it is inappropriate to label the titanium alloy a biocompatible material and the cobalt-chromium alloy an incompatible material. One cannot define the biocompatibility of a material without defining the location and function of the material. The complexities mentioned in the previous paragraphs may leave the practitioner wondering about the relevance of the definition of biocompatibility to dental practice. Yet there are profound consequences of this definition for practitioners. For example, the practitioner must always consider the health and habits of the patient when assessing the biologic response to materials. Is the patient diabetic? Does the patient smoke? If so, the response of the gingiva to placement of a crown may be affected. Does the patient drink many acidic liquids? The corrosion properties of partial denture alloys and the tissue response may be different. The practitioner must consider what he or she is asking the material to do and must not assume that, because a material is biologically acceptable in 1 role, it will be acceptable in a different role. Resin materials that are biologically acceptable as denture bases may or may not be acceptable as resin-based cements. Finally, the practitioner must monitor the patient over time. A patient who is not allergic to nickel today may become allergic in the future, from either oral exposure or exposure through other sources (jewelry, for example).

Biocompatibility is a property of a material and its environment

Biocompatibility is a property not only of a material, but also of a material interacting with its environment. In this sense, biocompatibility is like color (Fig. 2). We often ascribe color to a material, but color is a property of both the material and the materials interaction with light (its environment). Without the light interaction, there is no color. Ultimately, the color of the material depends on the light source, how the light interacts with the material, and the bias of the observer. Consider an example of this concept with dental implants. Under the proper conditions, a titanium alloy implant will osseointegrate with the bone over time.3 This means that the bone will approximate to within 100 of the implant with no intervening fibrous tissue. If a cobalt-chromium alloy is placed into
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HOW IS BIOCOMPATIBILITY RELEVANT TO DENTISTS?

Dentists potential concerns about biocompatibility can be organized into 4 areas: safety of the patient, safety of the dental staff, regulatory compliance issues, and legal liability.

Safety of the patient

One of the primary concerns of any dental practitioner is to avoid harming the patient. Evidence has shown that, although adverse reactions to dental materials are not common, they can occur for many types of materials, including alloys, resins, and cements.6-8 A national registry in Norway, where there are 4.3 million people and 3800 dentists, reported 674 adverse reactions to dental materials from 1993 to 1997.6 These adverse events occurred locally and systemically and involved all classes of dental materials. A 1 in 2600
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frequency of problems has been reported for dental casting alloys, including nickel-based alloys.7 Yet the number of adverse reactions may be underreported, and existing reports may not be accurate.8 Better documentation of the extent of these reactions is needed.7 One biocompatibility/patient safety issue that has been prominent in dentistry in recent years is the hypersensitivity of patients to dental biomaterials. Classically, this concern has focused on allergy to materials such as nickel or methacrylates. The incidence of nickel allergy in the general population ranges between 10% and 20% and is far more common in females than males.9 In patients sensitive to nickel, oral exposure to nickel may or may not elicit an allergic response, but these responses may be spectacular.8 There is also growing concern about the hypersensitivity of patients to resin-based materials10 and to latex.11 Although uncommon, patients can have severe or even fatal (anaphylactic) reactions to these materials.3 There have been recent reports of a growing incidence of contact sensitivity in children to a variety of substances, including dental materials. One report found that 49% of children had sensitivity to some type of material or food.12 The growing allergic history in children may portend an increasing need for dentists to be more aware of material allergies in adults in the future. Thus, there is evidence that the biomaterials used by dental practitioners can pose safety risks to patients. However, the evidence about harmful effects from materials is, more often than not, equivocal or incomplete. It therefore is every practitioners responsibility to decide whether the existing evidence has merit and to assess the risks of these issues in his or her own practice, taking into account each patients unique history.

in response to gloves, particularly latex gloves.14 Another study reported that 6.2% of dental staff were allergic to latex.11 The mechanisms by which materials cause problems through chronic exposure are not known, but there is evidence that some resin components such as 2-hydroxyethyl methacrylate (HEMA),15,16 tetraethylene glycol dimethacrylate (TEGDMA),15 and camphoroquinone17 are capable of directly activating immune cells. If the dental team also grinds laboratory materials such as acrylic resin, metals, or gypsum, then there is a risk from inhalation of particulates. Because particles less than 10 m in diameter cannot be filtered by the respiratory system,18 it is prudent to wear a mask when grinding or polishing any material. If laboratory personnel cast alloys containing beryllium, precautions must be taken to limit exposure to vapor from the alloy, as the vapor can cause berylliosis in the lungs.19,20 Reactions to many types of prosthodontic materials can be severe, career-threatening, and even life-threatening in rare instances.8

Regulatory compliance issues

Biocompatibility issues are closely linked to regulations that affect dental practice. An example of this link is related to dental amalgam. Because of the biologic concerns about mercury, regulators have considered monitoring and restricting the amount of mercury in waste water from dental practices.21-23 This debate has spurred considerable research on methods to eliminate particulate and elemental mercury from dental waste.21 Another example is the use of latex. Because of allergic reactions to latex (discussed previously), several US state legislatures have debated but not passed bans on latex gloves in dental and medical practice.11

Safety of the dental staff

In many situations, the risk of adverse effects of biomaterials is much higher for the dental staff than for the patient. The staff may be chronically exposed to materials when they are being manipulated or setting. The classic example of this problem is dental amalgam because the release of mercury vapor from amalgam during placement or removal is substantially higher than when it is undisturbed in the mouth.13 However, these types of issues also are relevant to casting alloys, resins, and other dental materials used in prosthodontics. For example, risks for dental staff appear to result from chronic contact with latex- and resin-based materials. Adverse effects from these materials range from cumulative irritation to allergenic responses.8 Ironically, gloves do not protect against contact with some materials because the materials are capable of moving through gloves.8,14 Furthermore, the gloves themselves may be a source of the problem. One study in Sweden reported that 15% of dentists (vs 9% in the general population) experienced itching on the hands
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Legal liability
Biocompatibility issues also influence liability issues that affect dental practitioners. Because dental materials can affect the well-being of patients and 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 (at best) emotionally and financially stressful to the practitioner.

ASSESSING BIOCOMPATIBILITY
In the last 30 years, the public and various government agencies have required some assurance that the materials used in dentistry are biologically safe and effective. Pressures to regulate materials have come from many sources, including the movement toward the ethical treatment of patients, an increased patient awareness of the risks involved in health care, and health practitioners concerns about litigation by
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patients. Unfortunately, assessment of the biocompatibility of a material is a complicated matter that may involve several sophisticated types of biologic tests, tests of physical properties such as corrosion, and riskbenefit analysis. The complexity of assessing the biocompatibility of materials is often bewildering and frustrating to practitioners and the general public. However, despite its complexity, biocompatibility testing of dental materials is currently the only means to try to assure the safety of the patient and dental team. One must always remember that the complexities of the current methods are preferable to using a new material not previously tested in humans.

Types of biocompatibility tests

Biocompatibility is measured with 3 types of biologic tests: in vitro tests, animal tests, and usage tests.24-26 It is unlikely that dentists will need to evaluate the results of these tests directly. However, it is important that practitioners, who must assume the direct legal risks of using materials in patients, understand how materials are approved for use. The following paragraphs describe the advantages and disadvantages of each type of biologic test so that practitioners will have a foundation for understanding biocompatibility issues. In vitro tests. In vitro biocompatibility tests are performed in a test tube, cell-culture dish, or otherwise outside of a living organism. These tests are quite diverse but generally place cells or bacteria in contact with a material. For example, a strain of bacteria may be used to assess the ability of a material to cause mutations (the so-called Ames test27,28), or a strain of fibroblasts may be grown on a culture plate and exposed to liquid extracts from a material. The effect of the material is generally determined by measuring the number, growth rate, metabolic function, or other cellular function of the cells exposed to the materials. In vitro tests have the advantages of being experimentally controllable, repeatable, fast, relatively inexpensive, and relatively simple. In addition, these tests generally avoid the ethical and legal issues that surround the use of animals and humans for testing. The primary disadvantage of in vitro tests is their questionable relevance to the use of a material in the mouth. Because these tests are performed outside of an intact organism, the many complex interactions that make up the biologic response in the body are not present. Consequently, in vitro tests may provide misleading results about the ultimate biologic response to the material. Animal tests. Animal tests for biocompatibility are different than in vitro tests because the material is placed into an animal, usually a mammal. For example, the material may be implanted into a mouse or placed into the tooth of a rat, dog, cat, sheep, goat, or mon206

key. By using a mammalian organism, this type of test allows the many complex interactions between the biologic environment and the material to occur. Thus, the biologic response is more comprehensive and more relevant than that obtained in in vitro tests. However, it is often difficult to control variables in animal tests. For example, the chewing habits of a sheep may alter the material in ways that are not relevant to humans. Furthermore, it often is difficult to quantitatively assess the biologic response because it is so complex. Ethical concerns and animal welfare issues are increasingly important in these types of tests. These tests are time-consuming and expensive. Finally, and most importantly to the practitioner, the question of relevance remains because there are always questions about the appropriateness of an animal species to represent the human response. Usage tests. Usage tests are essentially clinical trials of a material. In these tests, the material is placed into a human volunteer in its final intended use. The usage test is, by definition, the most relevant biocompatibility test; all other tests must be measured against it for relevance. However, usage tests have many complications and problems. They are expensive, time-consuming, extraordinarily difficult to control, and difficult to interpret, and they may be legally and ethically complex.

Correlating biocompatibility tests

Several studies have shown the problems of correlating in vitro, animal, and usage tests for biocompatibility.29-31 A classic example relates to zinc oxideeugenol cements. Clinical experience and clinical trials have shown conclusively that this cement has virtually no adverse pulpal effects, yet tests in animals (implanted subcutaneously) have shown significant inflammation, and in vitro cell-culture tests have shown that this cement can be severely toxic. Discrepancies such as these have led some researchers to question the usefulness of any test except the usage test to evaluate dental biomaterials.30 Today, researchers and regulatory agencies recognize that in vitro and animal tests play important roles in the biologic evaluation of dental materials.1 However, it is also recognized that the structure of any biocompatibility test is critical to its relevance. If meaningful data are to be obtained from biocompatibility tests, then the test procedures must be closely scrutinized to ensure that the testing conditions are as relevant as possible. For example, because zinc oxideeugenol cement is placed on dentin in clinical situations, in vitro or animal tests that do not replicate the presence of dentin give misleading results. Studies that have interposed a dentin barrier between the tissues or cells and zinc oxideeugenol cement better correlate with clinical results.19,32 For in vitro tests, the
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type of cells used, conditions of exposure, and type of response measured are critical. For animal tests, the animal system, site of implantation of the material, forces on the implant, and duration of the test are all important features.25,26

Using different biocompatibility tests together

For approximately 20 years, researchers have recognized that the most efficient, cost-effective, relevant way to evaluate the biocompatibility of materials is to use a combination of in vitro, animal, and usage tests.33 However, the ways in which these tests are used together and philosophies about the roles of each type of test have changed somewhat over the years. Early researchers proposed a pyramid scheme of unspecific toxicity, specific toxicity, and clinical trials (Fig. 3, a).34 Unspecific tests were those in which the conditions of the test did not necessarily reflect those of the materials use. Specific toxicity tests were those in which testing conditions were more relevant to the clinical use of the material. Approximately 10 years later, others proposed a similar pyramid scheme divided into primary, secondary, and usage tests (Fig. 3, b).33 This newer scheme expanded the scope of the tests beyond toxicity. Primary tests consisted of general cell toxicity, systemic toxicity in animals, bacterial mutagenic tests, and other types of in vitro tests. Secondary tests consisted of animal tests to measure allergy, mucosal irritation, and inflammation. Usage tests were equivalent to clinical trials. Both schemes used the pyramidal idea as a screening procedure. Only tests that passed the lowest level of the pyramid were considered for further testing. Likewise, only tests that passed the second tier were considered for clinical trials. Although efficient in time and cost, these schemes did not accommodate the reality that the initial tests were fraught with false-positive and false-negative results. Newer schemes have been developed that reflect the complexity of biocompatibility testing of materials (Fig. 3, c and d ). 1,34 Two of these schemes recognize several key points. First, all 3 types of biocompatibility tests continue to be useful throughout the evaluation of a material and during its clinical service. An in vitro test may be useful in the initial stages of material development to screen in promising materials, but it also may be useful to investigate a specific biologic response observed during clinical trials or after the introduction of a material to the market. Second, both schemes recognize the danger of screening out a material with a single type of test. Finally, both schemes recognize that the evaluation of the biocompatibility of a material is an ongoing process that evolves with the clinical experience of the material. The practitioner must keep especially this last point in mind.
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Fig. 3. Schemes for testing biocompatibility. Oldest scheme (a) used unspecific toxicity tests followed by specific toxicity tests and then clinical trials. Only materials that passed 1 level were tested further. Unspecific tests were not directly relevant to use of material. Second scheme (b) uses primary, secondary, and usage tests and is still commonly used today. Scheme b differs from scheme a because the former emphasizes many cellular reactions in addition to toxicity. As in scheme a, each test level screens for tests above it. Primary tests measure basic biologic properties such as toxicity or mutagenicity of material. Secondary tests assess more advanced properties such as allergenicity. Usage tests are equivalent to clinical trials. Newer schemes (c and d) for biocompatibility testing recognize need to use several types of tests together and treat evaluation of material biocompatibility as ongoing process.
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Regulatory approval of dental materials

Two regulations currently govern the use of dental materials: the American National Standard Institute/American Dental Association (ANSI/ ADA) document No. 41 (1979) and addendum No. 41A (1982) and the International Standards Organization (ISO) 10993 document (1993). Although these documents are different, the ANSI/ADA document is currently under revision to coordinate with the ISO document. The US Food and Drug Administration (FDA) regards dental materials as devices35 and uses the ANSI/ADA and ISO regulations as guidelines for determining the biologic safety of dental materials. The ADA also maintains a Seal Program for materials that pass the ADAs relevant specifications and standards. The FDA, ISO, and ANSI/ADA do not require specific biologic tests for approval of a new dental material. Rather, they place the responsibility on the manufacturer to present evidence for a compelling case for approval. The evidence consists of in vitro, animal, or usage tests that the manufacturer deems relevant to the material. Often, there are guidelines for the selection of these tests based on the type of material and its intended use. For example, in the ISO document, the types of recommended tests depend on the type and duration of body contact. For a dental casting alloy, body contact is viewed as an external device that communicates with dentin on a permanent (> 30 days) basis.36 For this type of device, the ISO recommends implantation tests and tests to measure cytotoxicity, sensitization potential, and genotoxicity. The structure of the specific tests also may be subjected to guidelines, but it is up to the manufacturer to defend any tests that are presented. It is important to remember that, in addition to the biologic tests, most materials also must meet specifications for other physical and chemical properties. In some situations, the FDA will grant approval based on a grandfather clause (510k). That is, a material may be approved if the case can be made that it is substantially equivalent to another material that has already been approved.37 Again, it is up to the manufacturer to defend the substantial equivalence argument.

This assumption is often not a good one. Second, new materials may be marketed with little clinical experience, and companies may rely heavily on in vitro and animal tests. In these cases, practitioners must question the relevance of these tests to the clinical use of the material, keeping in mind the limitations and pitfalls outlined previously. Even if clinical trials have been performed, practitioners must remember that clinical trials may be only 1 to 2 years in duration. The service life of many prosthodontic materials is much longer, and long-term effects may not be apparent in short-term trials. Third, practitioners must remember that the biologic evaluation of materials is an ongoing process. As more knowledge is acquired, opinions about safety and risk may change; it is legally and ethically dangerous to ignore new developments. Finally, the decision to use a new material is ultimately a riskbenefit decision that dentists must make for themselves. Practitioners should search for published evidence by unbiased researchers and consider the dental needs, esthetic desires, health history, and risk tolerance of their patients.

SUMMARY
Biocompatibility is especially relevant to prosthodontists and other restorative dentists because these practitioners rely heavily on materials that remain in intimate contact with living tissues for long periods. Decisions about the biologic safety of prosthodontic materials are as much philosophical as scientific. Because no material can be proven 100% safe, the decision to use a material in the mouth must balance the potential risks and benefits. Ultimately, each dentist must determine whether the benefits outweigh the risks for the patient under consideration. To avoid all risk is to deny the patient the tremendous benefits that materials have to offer. To assume too much risk may harm the patient and put the practitioner at legal risk. Technical tests and data, which improve over time, can aid practitioners, but the decision is ultimately a philosophical one that should involve the manufacturer, the patient, and the practitioner.

REFERENCES
1. Wataha JC, Hanks CT. Biocompatibility testingwhat can we anticipate? Trans Acad Dent Mater 1997:109-20. 2. Lemons JE. Dental implant biomaterials. J Am Dent Assoc 1990;121:716-9. 3. Albrektsson T. Direct bone anchorage of dental implants. J Prosthet Dent 1983;50:255-61 4. Black J, Sherk H, Bonini J, Rostoker WR, Schajowicz F, Galante JO. Metallosis associate with a stable titanium-alloy femoral component in total hip replacement. A case report. J Bone Joint Surg Am 1990;72:126-30. 5. Witt JD, Swann M. Metal wear and tissue response in failed titanium alloy total hip replacements. J Bone Joint Surg Br 1991;73:559-63. 6. Vamnes JS, Morken T, Helland S, Gjerdet NR. Dental gold alloys and contact hypersensitivity. Contact Dermatitis 2000;42:128-33. 7. Hensten-Pettersen A. Casting alloys: side-effects. Adv Dent Res 1992;6:38-43.

Critically evaluating new materials

How are these rather theoretical and technical aspects of biocompatibility measurement useful to dentists? Several points are appropriate. First, practitioners must be careful when evaluating sales literature that claims material biocompatibility. Marketing claims must be scrutinized carefully. What tests were used to evaluate the material? Does the company assume that the new material will behave like a related material?
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8. Hensten-Pettersen A. Skin and mucosal reactions associated with dental materials. Eur J Oral Sci 1998;106:707-12. 9. Hildebrand HF, Veron C, Martin P. Nickel, chromium, cobalt dental alloys and allergic reactions: an overview. Biomaterials 1989;10:545-8. 10. Rustemeyer T, de Groot J, Von Blomberg BM, Frosch PJ, Scheper RJ. Cross-reactivity patterns of contact-sensitizing methacrylates. Toxicol Appl Pharmacol 1998;148:83-90. 11. McCann D. Future of latex debated in states. Am Dent Assoc News 1998;29:1, 10-11. 12. Shah M, Lewis FM, Gawkrodger DJ. Patch testing in children and adolescents: five years experience and follow-up. J Am Acad Dermatol 1997;37:964-8. 13. Engle JH, Ferracane JL, Wichmann J, Okabe T. Quantitation of total mercury vapor released during dental procedures. Dent Mater 1992;8:176-80. 14. rtengren U, Andreasson H, Karlsson S, Meding B, Barregard L. Prevalence of self-reported hand eczema and skin symptoms associated with dental materials among Swedish dentists. Eur J Oral Sci 1999;107:496-505. 15. Rustemeyer T, De Ligter S, Von Blomberg BM, Frosch PJ, Scheper RJ. Human T lymphocyte priming in vitro by haptenated autologous dendritic cells. Clin Exp Immunol 1999;117:209-16. 16. Jontell M, Hanks CT, Bratel J, Bergenholtz G. Effects of unpolymerized resin components on the function of accessory cells derived from the rat incisor pulp. J Dent Res 1995;74:1162-7. 17. Rakich DR, Wataha JC, Lefebvre CA, Weller RN. Effect of dentin bonding agents on the secretion of inflammatory mediators from macrophages. J Endod 1999;25:114-7. 18. BruB KA, Jones TP, Williamson BJ. Electron microscopy of urban airborne particulate matter. USA Microsc Analysis 1997;Sep:11-2. 19. Covington JS, McBride MA, Slagle WF, Disney AL. Quantization of nickel and beryllium leakage from base metal casting alloys. J Prosthet Dent 1985;54:127-36. 20. Goyer RA. Toxic effects of metals. In: Klaassen CD, Amdur MO, Doull J, editors. Casarett and Doulls toxicology. 3rd ed. New York (NY): Macmillan; 1986. p. 582-635. 21. Fan PL, Chang SB, Siew C. Environmental hazard evaluation of amalgam scrap. Dent Mater 1992;8:359-61. 22. Letzel H, deBoer FA, Van t Hof MA. An estimation of the size distribution of amalgam particles in dental treatment waste. J Dent Res 1997;76:780-8. 23. Luz C. State societies can help with amalgam waste issues. Am Dent Assoc News 1999;22:6-9. 24. Hodgson E. Measurement of toxicity. In Hodgson E, Levi PE, editors. Modern toxicology. New York (NY): Elsevier; 1987. p. 233-85. 25. Hanks CT, Wataha JC, Sun Z. In vitro models of biocompatibility: a review. Dent Mater 1996;12:186-93.

26. Schuster GS, Lefebvre CA, Wataha JC, White SN. Biocompatibility of posterior restorative materials. J Calif Dent Assoc 1996;24:17-31. 27. Schweikl H, Schmalz G, Federlin M. Mutagenicity of the root canal sealer AHPlus in the Ames test. Clin Oral Investig 1998;2:125-9. 28. Stea S, Savarino L, Ciapetti G, Cenni E, Stea S, Trotta F, et al. Mutagenic potential of root canal sealers: evaluation through Ames testing. J Biomed Mater Res 1994;28:319-28. 29. Wennberg A, Mjr IA, Hensten-Pettersen A. Biological evaluation of dental restorative materialsa comparison of different test methods. J Biomed Mater Res 1983;17:23-36. 30. Mjr IA, Hensten-Pettersen A, Skogedal O. Biological evaluation of filling materials. A comparison of results using cell culture techniques, implantation tests and pulp studies. Int Dent J 1977;27:124-9. 31. Hensten-Pettersen A, Helgeland K. Evaluation of biological effects of dental materials using four different cell culture techniques. Scand J Dent Res 1977;85:291-6. 32. Hanks CT, Diehl ML, Craig RG, Makinen PK, Pashley DH. Characterization of the in vitro pulp chamber using the cytotoxicity of phenol. J Oral Pathol 1989;18:97-107. 33. Schmalz G. Modern concepts in biocompatibility testing of restorative materials. Trans Acad Dent Mater 1996;9:170-9. 34. Schmalz G. Concepts in biocompatibility testing of dental restorative materials. Clin Oral Investig 1997;1:154-62. 35. Improving patient care by reporting problems with medical devices. Definition of a medical device. Medwatch 1997;Sep:1-8. 36. International Standards Organization: biological evaluation of a medical devices. Part 1: guidance on selection of tests. 1st ed. ISO 10993-1. Geneva: ISO; 1992. 37. Alexander H. Substantially equivalent to what? J Appl Biomater 1994;5:375. Reprint requests to: DR JOHN C. WATAHA DEPARTMENT OF ORAL REHABILITATION SCHOOL OF DENTISTRY, MEDICAL COLLEGE OF GEORGIA 1120 15TH ST AUGUSTA, GA 30912-1260 FAX: (706)721-8349 E-MAIL: watahaj@mail.mcg.edu Copyright 2001 by The Editorial Council of The Journal of Prosthetic Dentistry. 0022-3913/2001/$35.00 + 0. 10/1/117056

doi:10.1067/mpr.2001.117056

New product news The January and July issues of the Journal carry information regarding new products of interest to prosthodontists. Product information should be sent 1 month prior to ad closing date to: Dr. Glen P. McGivney, Editor, UNC School of Dentistry, 414C Brauer Hall, CB #7450, Chapel Hill, NC 27599-7450. Product information may be accepted in whole or in part at the discretion of the Editor and is subject to editing. A black-and-white glossy photo may be submitted to accompany product information. Information and products reported are based on information provided by the manufacturer. No endorsement is intended or implied by the Editorial Council of The Journal of Prosthetic Dentistry, the editor, or the publisher.

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