BIOCOMPATIBILITY OF DENTAL MATERIALS AND TESTS

1. BIOCOMPATIBILITY
BY
DR.DEEPTHI

2.  CONTENTS
 Introduction
 Definition
 Requirements of dental materials
 Tests for evaluation of biocompatibility
 Allergic responses to dental materials
 Standards that regulate the measurement of
biocompatibility

3.  Biocompatibility of dental materials
 Reaction of other oral soft tissues to
restorative materials
 Reaction of bone & soft tissues to implant
materials
 Conclusion
 References

4. INTRODUCTION
 Biocompatibility refers to the study of
interaction of various materials with human
tissues.
 Biocompatibility is defined as the ability of a
material to function in a specific application in
the presence of an appropriate host response
(Williams 1987)
 Materials used in dentistry come into direct
contact with the hard tissues of the teeth, the
oral mucosa, the pulp & the periapical tissues.

5.  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.

6. Biocompatibility of dental materials is
characterized by many parameters such as:
1. Mutagenicity
2. Carcinogenicity
3. Genotoxicity
4. Cytotoxicity
5. Histocompatibility
6. Microbial effects Ability of the material to elicit
an appropriate biological response in a given
application in the body.

7. OTHER DEFINITIONS
 COMPATIBILITY: (To compath-to sympathize
with) A state 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.

8. 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.

9. HOW BIOCOMPATIBILITY IS RELEVANTTO
DENTIST
 Dentists potential concern about
biocompatibility can be organized into 4 areas
 Safety of the patient
 Safety of the dental staff
 Regulatory compliance issue
 Legal liability

10. 1. SAFETY OFTHE 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

11. 2. SAFETY OFTHE 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.

12. 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) the use of latex

13. LEGAL LIABILITY:
 Because dental materials can affect the well
being of patients & dental auxiliaries,
practitioners assume a legal risk when using
these materials.
 biomaterials causing harm to a patient is
probably rare.
 Nevertheless, when these problems occur, they
are emotionally & financially stressful to the
practitioner.

14. 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.

15. The activity of this interface depends on:
 1.The location of material.
 2. Its duration in the body.
 3.The properties of the material.
 4. Health of the host.

16. 4 types of interaction can take place:
1. Between the material and oral cavity.
2. Between the material and the pulp (Via the
dentinal tubules).
3. Between the material and periodontium.
4. Between the material and the periapical bone

17. ADVERSE EFFECTOF DENTAL MATERIAL
 Mutagenicity
 Carcinogenicity
 Genotoxicity
 Teratogenicity
 Cross reactive allergy

18. Concurrent AllergyToxicity :
 1. Immuno toxicity
 2. Systemic
 3. Local Inflammation Allergic Reactions Other
Reactions

19. 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

20. b) SYSTEMICTOXICITY
 Here site of application & site of adverse
reactions are different.
 Almost all dental materials release substances
into the oral cavity, from where they may enter
the systemic circulation via different routes.
According to the time frame,
 1. Acute (up to an exposure period of 24 h)
 2. Sub acute (up to 3 months)
 3. Chronic toxicity are differentiated.

21. c)LOCALTOXICITY
 Substances released from dental materials may
generate a reaction (e.g., inflammation or
necrosis) in adjacent tissues such as oral
mucosa/ gingiva, pulp or alveolar bone.
 release of substances from the dental material
is not always responsible for local irritation.
 There may be other factors like:
 1. Bacterial accumulation on the surface, at the
margin, or under a material.
 2. Mechanical/physical irritation, such as
pressure caused by dentures.

22. INFLAMMATION :
 The inflammatory response is complex & it
occurs to ward off some threat.
 Histologically, the inflammatory response is
characterized by
 1. Edema of the tissue.
 2. Inflammatory cells infiltration such as
neutrophils (in the short term) or monocytes and
other lymphocytic cells(in the long term)

23. ALLERGY :
 Allergy is an abnormal antigen – antibody
reaction to a substance that is harmless to most
individuals.
 It is not dose dependent.
 These allergic reactions are also called
Hypersensitivity reactions & are mediated by IgE

24. Four different types of allergic reactions are
differentiated:
 1. Immediate reaction, anaphylactic (Type I).
 2. Cytotoxic reaction (Type II).
 3. Formation of immune complexes(Type III).
 4. Delayed reaction (Type IV).
 ALLERGIC REACTIONS ELICITED BY DENTAL
MATERIALS CAN OCCUR INTRAORALLY( OR)
AS REMOTE REACTIONS EXTRAORALLY.

25.  Types I, II, and III are mediated by antibodies,
whereas type IV is primarily imparted by cells.
 Dental materials may cause allergies of type I
(immediate reaction) and type IV (delayed
reaction).
 Examples
 1. Immediate reaction is Contact urticaria
following occupational exposure to latex
proteins in disposable gloves.
 2. Delayed reaction : Allergic reaction to
components of the root canal sealer AH26.

26. ALLERGY
CONCURRENT- ALLERGY
CROSS-ALLERGY
 If an individual is allergic to a particular
element, then it may be assumed that he
will also allergic to chemically similar
elements. For e.g.–Nickel and palladium.
 It is generated by 2 allergen that are
frequently present at same time within a
material oral environment. e.g.–Ethylene
glycol dimethacrylate (EGDMA) Hydroxy
ethyl Methacrylate (HEMA)
 Allergy to nickel, palladium, and cobalt
was confirmed by patch testing

27. OTHERREACTIONS
 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, Be are known mutagens

28.  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.

29. LEVELS OF BIOCOMPATIBILITY
 1. GENERAL BIOCOMPATIBILITY: Determines
the toxicity of the material at a cellular level.
 2. IMMUNOLOGICALBIOCOMPATIBILITY:
Determines of how an individual reacts to the
material.
 Tests performed to determine the body’s
immunological response are:
 1. Clifford Materials ReactivityTest
 2. Kinesiologic testing.

30. MEASURINGTHE
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

31.  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.

32.  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.

33.  According to phillips there are three basic types
of tests used to measure biocompatibility of
dental materials:
 InVitroTests
 AnimalTests
 UsageTests

34.  TEST PHASE III, IV
 INVITRO SMALLANIMALS [GUINEA
PIGS,MICE, RATS] LARGERANIMALS
[DOGS] / PRIMATES [MONKEYS] HUMAN
 INVIVO ANIMALTEST USAGETEST INITIAL
TEST SecondaryTest [Animals]

35.  The initial tests (Phases I and II)
are of a short duration, simple
and cost effective.
 Only after completing initial
test, the material progresses
through the testing hierarchy
i.e 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.

36.  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.
 Phase I II – Initial test
 Phase III – Animal test
 Phase IV– Clinical trails
Craig 11th edition

37. INVITRO ANIMALTEST USAGETEST FOR
DETECTING CELL FUNCTION& METABOLISM
 The inhalation toxicity tests
 1. Pulp/ Dentin test
 2. Pulp capping and Pulpotomy usage tests
 3. Endodontic UsageTest
 4. Intra osseous ImplantTest

38.  INVITROTESTS :
 Done in some biological system outside a living
organism.The contact can be either:
 Two types of cells can be used for in vitro tests.
 Direct Material contact directly the cell system.
 Indirect Barrier is present between the material
and the cell system.

39.  CYTOTOXICITY TESTS DEFINITION:To cause toxic
effects at the cellular level.
 DIRECT CONTACTTEST
 Cells are placed in a well of a cell-culture dish, where
they attach.
 The materialis then placed in the test system. If the
material is not cytotoxic, cells will remain attached to
the well and will proliferate over time.
 If the material is cytotoxic, cells may stop growing or
exhibit cytopathic changes or detach from the well.

40. MEMBRANE PERMEABILITYTESTS :
 It is based on the fact that loss of membrane
permeability is equivalent to or very nearly
equivalent to cell death.
 Here dye issued to measure, which can pass
through a cell membrane.

41. Dyes are of two types:
 1.Vital dyes:They are actively transported
into viable cells, where they are retained
unless cytotoxic effects increase the
permeability of the membrane. Ex:Neutral
red
 2. Non vital dyes:These are not actively
transported and are taken up if membrane
permeability has been compromised by
cytotoxicity. Ex:Trypanblue

42. TESTSTHAT USE BARRIERS [INDIRECTTESTS]
 1. Agar diffusion test/ tissue culture overlay test
method
 2. Millipore filter assay
 3. Dentin barrier tests

43. Agar Diffusion testing :
 A monolayer cell culture is used.
 The cell stained with neutral red vital stain dye.Then
agar layer is placed over the cells on which the test
material is incubated for 24 hrs
 Agar forms a barrier between the cells and the
material.
 If the test material is cytotoxic, it will lead to loss of
dye within cells as they lyses.
 A cellulose acetate filter having 0.45µm filter is used

44.  Milli pore filter assay :Cells are grown on one
side of the filter and the test material placed on
the opposite side of filter.
 Any leachable substance from the test material
must diffuse through the pores to exert a
cytotoxic effect on the cells.

45. Dentin Barrier testing :
 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.
 B. Showing the device to hold the dentin disk
 C. Showing collection fluid (cell culture medium or
saline) is on the other side of the disk.

46. MUTAGENESISASSAYS :
 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.

47.  2. Styles cell transformation test : Done in
mammalian cell done as alternate to bacterial
test.

48. TESTS FOR CELL METABOLISMOR CELL
FUNCTION
 Bio synthetic or enzymatic activity of cells are
used to measure cytotoxicity of the test
material.
 E g.Tests that measures DNA synthesis or
protein synthesis
 1. MTT test it’s cell liability test
 2. NBT (Nitroblue tetrazolium)
 3. XTT test
 4.WST ( aWater –soluble tetrazolium)

49. TestAdvantages Disadvantages InVitro test
 1. Short duration
 2. Simple
 3. Cost effective
 4. Good control over experiment
 5. Large scale screening
 6. Can best and Relevance to in vivo is
questionable

50. IMPLANTATIONTEST
 Materials tested in this way are the ones that
directly contact soft tissue & bone like
 1. Implant materials.
 2. Materials used for endodontic and
periodontal therapy.
 Amalgams and alloys are also tested because
the margins of the restorative materials
contact the gingiva.
SHORTTERM IMPLANTATION
TEST
Material is placed for 1-11 weeks
LONGTERM
IMPLANTATIONTEST
Material is placed for 1- 2
years

51. THE DERMALTOXICITYTESTS
 The test material is injected intra dermally &
skin hypersensitivity reactions are checked.
 For the main test, the highest concentration of
the test material that causes no more than slight
erythema and edema is selected

52. THE INHALATIONTOXICITYTESTS :
 An aerosol of the test material is sprayed 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.

53. Test Advantages InVivo test
1. Allows complex systemic interactions.
2. More relevant than in vitro tests.
Disadvantages :
1.Time consuming.
2. Expensive.
3. Legal ethical concerns.

54. PULP / DENTINTEST :
ClassV cavities are prepared as atraumatically as
possible and are then filled with the test material.
 After a period of days to several months, the teeth
are removed and histologically examined to check:
 1. Bacterial penetration
 2. Inflammation
 3. Odontoblastic reaction Promising test materials
induce the least inflammatory response in the pulp.
 If a response is produced, the time required to
disappear is also measured

55. PULP CAPPINGAND PULPOTOMY USAGE
TESTS :
 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.
 Observations are made of dentinal bridge
formation directly against the capping
material.

56. ENDODONTIC USAGE TEST :
 the pulp is completely removed from the
pulp chamber and root canals replaced by the
obturating test material and control material

57. TEST PROGRAMS FORTHE BIOLOGICALTESTING
OF DENTAL MATERIAL
 Test method Describe the manner in which test
are to be used.
The test programs that can be adopted are :
 Linear Progression of tests
 Non Linear Progression of tests

58.  Mjör 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

59. Non Linear Progression of tests :
 Mjör in 1977 he modified the linear paradigm to
a non-linear pattern, where simultaneously all
three tests would be performed on the tested
material

60.  STANDARDSTHAT REGULATETHE
MEASUREMENTOF 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.

61. 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
materials screening and divides testing into
initial, secondary, and usage tests. Linear
progression test program
 Document No 41. is currently being revised , but
the revision is not complete, so the 1982 version
is still in force.

62.  ISO STANDARD 10993: It is the international
Standards for testing the biocompatibility of
dental materials.
 Unlike ANSI/ADA Document No. 41, the IS0
10993 standard is not restricted to dental
materials.
 This document was first published in 1992, but
modified versions are updated periodically.

63.  Test for genotoxicity , carcinogenicity, and
reproductive toxicity ISO 10993 – 4: 1992
 Tests for materials that interact with blood ISO
10993 – 5: 1992
 Tests for cytotoxicity : In vitro methods ISO
10993 – 6: 1992
 Tests for irritation and sensitization ISO 10993 –
11: 1992
 Tests for systemic toxicity Some relevant parts
that covers biological testing are given below 60

64.  Silver Amalgam Systemic toxicity Elemental
Mercury can lead to systemic toxicity.
 It can enter into human body through the skin,
by ingestion, or by inhalation of mercury vapors.
 Inhalation is the most common route of entry
among patients and dental personnel

65. Systemic toxicity :
 The following are the sources of mercury
exposure in the dental office:
 Improper storage of mercury .
 Exposure during manipulation i.e trituration,
insertion
 Exposure during finishing and polishing.
 Removal of old amalgam restorations.
 Safe level of mercury exposure in the dental
office is 50 µg Hg / Cubic Meter of air /day

66. LocalToxicity Pulp Reactions:
 Reduced number of odontoblast.
 Dilated capillaries.
 An inflammatory cell reaction is seen in the
odontoblastic layer, following the direct
condensation of amalgam in deep cavities.
 Oral Mucosa reactions:
 Gingivitis
 Bleeding gums
 Bone loss around teeth
 Desquamation of buccal or lingual mucosa
AmalgamTattoos caused by entry of dental
amalgam into the soft tissues.

67.  Allergic reactionType IV – Delayed allergic type
reaction may be seen in the oral mucosa in
contact with the restorations.
 They manifest as Oral Lichenoid Reactions,
which resolve on removal of the restorations.
Other reactions .
 No evidence of mutagenic or carcinogenic
reactions.

68.  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 but a fluorescent tube without
phosphors, [a pure mercury vapour discharge
lamp].

69.  By the principles of atomic absorption
spectrophotometry, the only cold vapour that
could absorb the wavelength of mercury
emission light and cast a shadow would be that
of mercury itself.
 The filling was dipped in 1100 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.

70. DENTAL CASTINGALLOYS
 Systemic toxicity :The number of elements
released from the dental alloys is far below the
dietary intake; for e.g. the amount of zinc
released (< 0.1µg /day ) is far below the daily
dietary intake (14,250µg /day).
 No studies have demonstrated systemic toxicity
due to cast alloys.

71. LocalToxicity :
 Casting alloys that are in intimate contact with
the gingiva will form a“ microenvironment
 When there is a release of elements from the
alloys, and if it is present in more conc. in the
sulcus than in saliva, then epithelial cells of the
sulcus will more prone to cytotoxicity.
 All casting alloys release elements, but all
elements are not cytotoxic.

72.  LocalToxicity Ni, Cr, Co - Cytotoxic.
 Ni, Cu - Gingival inflammation.
 Allergic ReactionsThe incidence of nickel allergy
is 15% and that of Co and Cr is 8%.
 Cross –reactive allergy can occur for Pd and Ni.
 Lichenoid reactions have also been reported in
the oral mucosa adjacent to casting alloys.

73.  Other ReactionsThrough Ni ions by themselves
are weak mutagens, Ni subsuflide is a
documented carcinogen.
 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

74. CERAMICS:
 Systemic toxicity 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.
 LocalToxicity Most ceramics are biocompatible .

75. Allergic Reaction :
 No reported allergic reaction.
 Other Reaction Zirconium oxide ceramics show
some amount of radioactivity due to
contaminants such as thorium and uranium.
 However, the radioactivity level is not very
significant

76. RESTORATIVE MATERIALS :
 1.Tooth Coloured Cements
 2.Tooth Coloured resins 3. Non resin cements,
Liners &Varnishes
 TOOTHCOLOURED CEMENTS
 1. Silicate Cements
 2. Glass Ionomer Cement

77. 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.

78. GLASS IONOMER CEMENTS :
 Systemic toxicity :No evidence of systemic
toxicity with conventional or resin modified
glass ionomer cement (RMGIC).
 Local toxicity 1. Unset GIC is cytotoxic to the
pulp.
 The cytotoxicity is attributed to the acidity of
the cement and release of fluoride ions .
 2. Dentin present between the pulp and the
cement acts like a buffer

79. Local toxicity :
 Dentin should be moist before the cement is
placed in the prepared cavity.
 If dentin is over dried , the cement will withdraw
water needed for the setting reaction from the
dentinal tubules, which will result in pain.
 RMGIC is cytotoxic in the uncured stage but is
only slightly cytotoxic after curing.

80. Allergic reaction :
 Conventional GIC : No reported allergic
reaction.
 RMGIC : Allergy due to HEMA in some
individuals. [So wearing of gloves is
recommended to avoid direct contact.]
 Other reactions No evidence of mutagenic or
cariogenic reactions.
 Allergic skin reactions to methacrylate-based
dental materials

81. TOOTHCOLOURED RESINS :
 Unfilled resins
 Resin Composite
 Resin modified GIC
 Polyacid Modified Composite Resins
 Dentin Adhesives
 Pit & Fissure sealant

82. COMPOSITE RESIN&POLYACID MODIFIED
COMPOSITE RESIN :
 Systemic toxicity :No evidence of toxicity. But,
there is some concern regarding BPA (bisphenol
A ), 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

83. LocalToxicity :
 Cytotoxic substances such asTEGDMA & HEMA
can be released from unset or partially cured
composites.
 These components can diffuse through dentin
and cause pulpal inflammation

84. Allergic Reaction :
 Primary risk factor related to composite Bis -
GMA ,TEGDMA, and Methylmethacrylate
(MMA) can act like allergens in some individuals.
 They can produce aTYPE IV delayed
hypersensitivity reaction.
 NOTE: Dental personnel should wear gloves
while handling composite. However, these
monomers can penetrate through latex or nitrile
gloves.
 Hence, Polychloroprene (neoprene) gloves are
recommended

85. NON RESIN CEMENTS, LINERS &VARNISHES
 Calcium Hydroxide
 Varnishes
 Zinc Phosphate Cement
 Zinc oxide Eugenol Cement
 Zinc Polycarboxylate cement

86. Systemic toxicity :
 No reported systemic reaction.
Local toxicity :
 Pulp reaction Indirect pulp capping material:
 1. Exerts antibacterial effect.
 2.Tertiary dentin formation.
 3. Decreases the permeability of dentin.
 NOTE:Tertiary dentin will be triggered only if
the remaining dentin thickness(RDT) is 5 to 10
µm.

87. CALCIUM HYDROXIDE
 Direct pulp capping material: When in direct
contact with the pulp, produces superficial
coagulation necrosis.
 This acts like a stimulus for the differentiation of
secondary odontoblasts that lay down tertiary
dentin.

88. ZINC PHOSPHATE CEMENT :
 Systemic toxicity :No reported systemic reaction.
LocalToxicity Pulp reaction
 1.The acidity of the cement initially after mixing is
very high due to presence of phosphoric acid (pH is
around 3.5 during application).
 Subsequently, it increases towards neutrality within
24-48 hours.
 NOTE 1:The greater the remaining dentin thickness
(RDT),the lesser will be the degree of acid
penetration.
 NOTE 2: A thin consistency of the cement will
provoke a stinging sensation called Phosphoric acid
sting.

89. Precautions to be taken are as follows:
 1.The powder/liquid ratio should never be
reduced to increase the working time, as this
increases the acid content.
 2. Pulpal protection should always be done with:
 Calciumhydroxide
 Cavity varnish

90. Allergic Reaction :
 No reported allergic reaction
 Other reaction :No evidence of mutagenic or
carcinogenic reaction

91. ZINE OXIDE EUGENOL CEMENT :
 Systemic toxicity No reported systemic reaction
 LocalToxicity :Pulp reaction
 1.The cement can produce a cytotoxic reaction
when directly applied to the pulp.
 2. If there is a complete dentin layer between
the pulp and the cement, no inflammatory
reaction will occur. [LEAST IRRITATING OF ALL
THE CEMENTS :
 pH 6.6 -8 i.e. Mild pulpal response]

92.  1. Eugenol has the capability to block
transmission of action potentials of the
nerves, hence, this cement has an obtundant
(soothing) effect when used in deep cavities.

93. Allergic Reaction :
 Eugenol can induce an allergic response in some
individuals.
 Allergic contact dermatitis has also been
reported in dental personnel handling the
cement.
 Other reaction No evidence of mutagenic or
carcinogenic reaction

94. ZINC POLYCARBOXYLATE CEMENT :
 Systemic toxicity No reported systemic reaction.
 Local toxicity 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 areas follows: Liquid is more
rapidly neutralized by the powder i. e its pH rises
more rapidly than Znphosphate.
 The polyacrylic acid molecule is larger in diameter
than the dentinal tubules which limit its diffusion
into the tubules

95. Allergic Reaction :
 No reported allergic reaction
Other reaction
 No evidence of mutagenic or carcinogeni
creaction

96.  IMPRESSION MATERIALS
 The clinical relevance of tests for the assessment of
the cytotoxicity of dental materials is widely
recognized.Various types of tests are covered in ISO
10993-5.
 Biological Evaluation of Medical Devices:Tests for In
Vitro Cytotoxicity. Comparing the cell cytotoxicity
for different impression materials reveals
 that polysulfide materials result in the lowest cell
death count and the set polyether impression
material
 produces the highest cell cytotoxicity scores Similar
results are also observed in multiple exposure tests.

97.  The most likely elastomer-induced
biocompatibility problem occurs when a
fragment of impression material is trapped in
a patient’s gingival sulcus.
 fragments of impression materials have
been found in soft tissues, under the
periosteum, in the spongy bone, and in the
maxillary sinus.

98.  This can also occur in implant dentistry,
particularly during second-stage implant
surgery or during single-stage surgery.
 A foreign body of impression material is
known to cause a severe gingival
inflammation, which may be misdiagnosed as
an adverse effect of the tooth preparation or
cementation.

99.  Local effects:
 Contact dermatitis from the polyether,
especially as experienced by dental assistant.
 Systemic effects:
 no cytotoxic effects have been reported.
 Allergic Reaction:
Some concerns exist about hypersensitivity
potential of the polyether catalyst system.

100.  Biosafety is the prevention of large-scale loss
of biological integrity, focusing both on
ecology and human health.These prevention
mechanisms include conduction of regular
reviews of the biosafety in laboratory
settings, as well as strict guidelines to follow.
 Biosafety is used to protect from harmful
incidents.

101. ENDODONTIC MATERIALS :
Formocresol
 The toxic properties of formocresol reported
are
 Permanent tooth hypoplasia.
 Systemic distribution
 Dermatitis ad pharygitis
 Antigenesity
 Mutageicity and carcinogenicity

102. ROOT CANAL SEALERS :
 Systemic toxicity
 There is no systemic toxicity is reported with
most of the sealers.
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

103. Local toxicity :
 1. Para formaldehyde containing sealers : Severe
cytotoxic response.
 They can irreversibly affect nerve conduction
and result in paresthesia.
 2. ZOE based sealers : Moderate cytotoxic
response.
 A ZOE sealer without paraformaldehyde was
tested and found to be nonmutagenic [209], but
paraformaldehyde-containing endodontic
sealers tested positive

104.  at conc above 2.4mM eugenol irreversibly
inhibited nerve conduction, and with
formaldehyde and formocresol it was
concentrations above 8.9mM and 6.7mM. Due to
high solubility of formaldehyde in water, this
concentration is easily reached, and can cause
damage. All toxic concentrations are achievable
with current sealers, depends on what and how
much contacts the nerve directly.
 Pal Brodin (EDT ‘88): Lit review on parasthesias
(great table) and nerve study showed neurotoxic
effects of sealers

105. LocalToxicity :
 Resin – based sealers: Cytotoxicity is less
than that of para formaldehyde
containing sealers.
 4. Ca Hydroxide based sealers: Less
cytotoxic than above mentioned sealers.
Some amount of neural damage has been
reported with these sealers.

106.  Polyketone-Based sealers :One sealer based
on polyketone (Diaket) has been on the
market since 1952 .
 This material sets via the formation of a
chelate complex composed of a ketone and
zinc. No data are available regarding the
release of toxic substances.

107.  Intraosseal implantation of this endodontic
sealer caused a chronic inflammatory
reaction when the material was mixed in a
sealer-like consistency

108. Allergic Reaction :
 1. Paraformaldehyde can also act as an allergens
and can even result in an anaphylactic reaction.
Respiratory and cutaneous reactions as well .
 2. ZnoE sealers: allergic because of eugenol.
dental personnel have shown allergic contact
dermatitis due to eugenol-containing materials

109. 3. Resin – based sealers: Allergic because of
bisphenolA Diglycidyl ether (BADGE) which is
an important contact allergen.
Other Reactions Sealers having mutagenic
potential are:
1. Paraformaldehyde containing sealers
2. Unset resin –based sealers

110. OBTURATING MATERIALS :
 Systemic toxicity :No systemic toxicity is
reported for any of the obturating material.
 Local toxicity 1. Silver points used earlier as
obturating materials are no longer used due to
their corrosion potential.
 Gutta – percha is only slightly cytotoxic [in cell
culture].
 For thermoplasticized guttapercha, exceeding
the recommended temperature while using–
techniques can result in damage to periodontal
tissues

111.  Allergic reactions to gutta-percha seem to be
very rare as well. only one case of a
suspected allergic reaction has been
documented [33].
 Gutta-percha was applied beyond the root
apex in a female patient who was allergic to
latex..

112.  The operator did not wear latex gloves.
 Pain, lip swelling, and a diffuse urticaria
occurred after the endodontic treatment

113.  The gutta-percha point was removed 4 weeks
later.
 Thereafter, the patient’s symptoms
disappeared.
 It should be noted that gutta-percha and
latex are natural products derived from trees
that belong to the same botanical family

114. Local toxicity :
 Resilon points : Cytotoxic probably due to the
presence of hydroxyethyl methacrylate (HEMA).
 MTA : Least cytotoxic of all dental material.The
cytotoxicity is similar to the chemically inert
titanium alloy.
 MTA also has an osteogenic potential

115. Allergic Reaction :
 Allergy to gutta – percha is very rare.
 Proteins of gutta – percha are removed by a
purification process. Use of impure forms of
gutta – percha may result in an allergicreaction.
 Some manufacture use Balata,a dried juice of
BrazilianTress, to make gutta percha points.
Balata is known to cause cross – reactivity with
latex.
 Other Reactions No mutagenic or carcinogenic
effect is reported with obturating materials

116. LATEX MATERIALS :
 Systemic toxicity: No systemic toxicity is
reported with it.
 Allergic Reaction :The incidence of latex allergy
is about 9.7% and 6% among patients and
dental staff,respectively.
 Latex products can produce either:
 1.Type 1immediateatopic/anaphylactic reaction
 2.Type IV delayed hypersensitivity reaction
(Allergic contact dermatitis)

117. Allergic Reaction :
 Type I reaction : Due to proteins present in natural
latex
 Type IV : 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.
 Other Reactions :No Mutagenic or carcinogenic
effect is reported with latex rubber

118. CONCLUSION :
 It is mandatory for the clinician to know the
medical history ,allergic history of the patient.
 To know &understand the biocompatibility of
the dental materials, so as to provide maximum
advantage & minimum risk to the patient.

119. REFERENCES :
 Science of dental materials-Philips,10th edition
 Restorative dental materials-G.Craig &John M.
Powers,11th edition.
 Gottfried Schmalz Dorthe Arenholt-Bindslev
Biocompatibility ofDental Materials