Of Gold and Ceramic Dental Restorations

Home , Dental porcelain, Dental restoration

ORIGINAL ARTICLE Assessment of exposures and potential risks to the US adult population from wear (attrition and abrasion) of gold and ceramic dental restorations

G. Mark Richardson1, Scott R. Clemow2, Rachel E. Peters3, Kyle J. James3 and Steven D. Siciliano3

Little has been published on the chemical exposures and risks of dental restorative materials other than from dental amalgam and composite resins. Here we provide the ﬁrst exposure and risk assessment for gold (Au) alloy and ceramic restorative materials. Based on the 2001–2004 US National Health and Nutrition Examination Survey (NHANES), we assessed the exposure of US adults to the components of Au alloy and ceramic dental restorations owing to dental material wear. Silver (Ag) is the most problematic component of Au alloy restorations, owing to a combination of toxicity and proportional composition. It was estimated that adults could possess an average of four tooth surfaces restored with Au alloy before exceeding, on average, the reference exposure level (REL) for Ag. Lithium (Li) is the most problematic component of dental ceramics. It was estimated that adults could possess an average of 15 tooth surfaces restored with ceramics before exceeding the REL for Li. Relative risks of chemical exposures from dental materials decrease in the following order: Amalgam4Au alloys4ceramics4composite resins.

Journal of Exposure Science and Environmental Epidemiology (2016) 26, 70–77; doi:10.1038/jes.2015.17; published online 25 March 2015 Keywords: dental materials; exposure; risk; gold; ceramics

INTRODUCTION manufacturing technologies.28 Ceramics may also be used for 17 25 One hundred and thirty million dental restorations are placed veneers and be fused to a metal base for crowns and bridges. annually in the US population.1 Exposure to the components of The overall rate of use of Au alloys and ceramics for dental 29 dental materials occurs in people with dental ﬁllings. Most restorations is relatively low, due to high cost, but their usage is – o attention has been focused on mercury from dental amalgam2 5 increasing. US statistics in the mid-1990s indicated that 2% of all restorations placed were either Au alloy or ceramic.27 In 2005, and to a lesser extent on bisphenol-a (BPA) from composite 1 resins.6–10 However, no attention has yet been directed toward they represented 21.8% of restorations placed. ﬁ exposures to components of gold (Au) alloy or ceramic restora- This paper presents the rst estimates of exposure and potential tions, despite the rapid increase in preference for non-amalgam risk from components of Au alloy and ceramic dental restorative 1,11–14 materials. The work was undertaken in a manner consistent with alternatives. Component elements of Au alloy and ceramic 4 restorations have been observed in saliva at least 3 months after that of a previous assessment of dental amalgam, in order to placement,15 and elevated levels in blood due to Au alloys maximize the direct comparability of exposure and risk estimates. continue for at least 15 years post-placement,16 so exposures from these materials do occur. Au alloys have been used for dental applications longer than METHODS 17–19 has amalgam, and are the preferred restorative materials of Population-Level Assessment 20 dental clinicians, particularly for their own teeth. Au alloys are Population level, scenario-based chemical exposure and risk assessment 21 primarily used as foils, inlays, onlays, crowns and dental wiring, but requires use of probabilistic methods, such as Monte Carlo analysis.30 In are also used as fashion jewelry (“grillz”) on teeth.22 Softer alloys are this study, we combined the data from the NHANES (see NHANES Data generally used for smaller single-surface preparations, whereas section), including statistical weighting of survey participants, with other harder alloys are used for larger inlays, onlays and crowns.23 Monte Carlo methods to provide a more accurate extrapolation of Dental ceramics have been used in dentistry since the 1800s,24 exposure and risk to the entire US adult population. and are generally composed of feldspar porcelain, with newer formulations containing various alkali metals and other metal 25,26 Restorative Composition components to improve workability, strength and stiffness. The Au content of Au dental alloys ranges widely,21 but typically ranges They are used to produce inlays via external preparation from 40% to 77% Au by weight.23 The other common components are 25,27 from casts and molds of prepared cavities and, starting in the silver (Ag), copper (Cu), indium (In), palladium (Pd), platinum (Pt) and zinc 1980s, employing computer aided design/computer aided (Zn). Au alloy composition is summarized in Table 1.

1Stantec Consulting, 400–1331 Clyde Avenue, Ottawa, Ontario, Canada; 2SNC-Lavalin Environment, Ottawa, Ontario, Canada and 3Interdisciplinary Toxicology Program, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. Correspondence: Dr. George M. Richardson, Stantec Consulting, Risk Assessment Team, 400 – 1331 Clyde Avenue, Ottawa, Ontario K2C 3G4, Canada. Tel.: +613 410 2748. Fax: +613 722 2799. E-mail: [email protected] Received 23 October 2014; revised 12 January 2015; accepted 29 January 2015; published online 25 March 2015 Exposures from gold and ceramic dental materials Richardson et al 71

Table 1. Typical composition of gold alloy and ceramic dental restoratives, and component reference exposure levels.

Minimum % Maximum % Most typical range % Reference exposure level Dental Material Component composition composition composition (μg/kg-day)

Au alloya Au 4.4 88.9 40–77 None available Ag 0 64.5 14–40 5b Cu 0 57 7.5–21 141c Pd 0 47.7 1–92d Zn 0 10 0–3 300b Pt 0 77.3 1–17 2.6d In 0 9 0–4.5 8.3e Density (g/cm3) 11.5 18.8 11.5–18.8

f g Ceramic SiO2 17 80 46–80 25,000 h AlO2 02211–22 1000 MgO 0 17 0–5 6000g h Li2O 0 19 0–19 2 i TiO2 0 4.5 0–3 4000 h SnO2 0 5.25 0–5 600 b B2O3 07 0–7 200 BaO 0 2 0–2 200b ZnO 0 8 0–8 300b Density (g/cm3) 2.43 2.52 2.43–2.52 aReferences 21, 49–60. bReference 61. cReference 62. dReference 63. eReference 64. fReferences 65–72. gReference 73. hReference 74. iReference 75.

Table 2. Summary of NHANES (2001–2002 and 2003–2004 surveys combined) data for adults ≥ 21 years of age.

Age range Total survey Number of participants Average number of restored Maximum number Age group (years) sample size (N) with restored teeth tooth surfacesa of restored surfaces

Adults 21–59b 5673 4454 17.9 128 Seniors ≥ 60 3151 2031 28.9 109 Survey totals 8824 6485 US adult population represented 189,932,347 151,299,412 aExcludes survey participants having no dental restorations. bAge range includes persons up to 59 years and 11 months of age.

Silicon dioxide (SiO2) has the highest percent composition in dental Owing to the relatively high cost of both Au alloy and ceramic dental ceramics, typically constituting between 46% and 80% by weight. Other restorations, only adults (aged 21 years and older) were considered likely common components are oxides of aluminum (Al), magnesium (Mg), to possess these restorations. Adults represented 8824 survey participants lithium (Li), titanium (Ti), tin (Sn), boron (B), barium (Ba) and zinc (Zn; see from the NHANES data set (Table 2). Table 1). NHANES also establishes the statistical weight of each participant. For purposes of dose calculations, each participant record within the Therefore, the exposure estimate derived for each participant of the 2001– NHANES data set was assigned an Au content, or SiO2 content for ceramics, 2004 NHANES surveys was multiplied by their respective weighting factor selected randomly between the minimum and maximum “most typical to accurately adjust distributions of exposure to mirror the actual US adult range” percent composition (Table 1). The percent compositions of all population. Owing to survey merging, 4 year statistical weights were 31 other components were then set randomly within their reported limits, applied as recommended for NHANES. The total US adult population but adjusted as necessary to ensure that total percent composition represented by the NHANES data set was 189,932,347. equated to 100%. This randomization procedure was deemed superior to a simple assumption that each participant be assigned the same composi- Estimating Exposure Due to Wear tion, such as the maximum percent composition of Au, or Ag or other Loss of material from a dental restoration into the oral cavity for component. subsequent ingestion can be caused by: attrition — physical wear of the restoration against opposing tooth surfaces in occlusion; abrasion — physical wear because of the friction with foods and other abrasive items; NHANES Data corrosion — chemical degradation of the restoration; and simple leaching 4 Consistent with the assessment of dental amalgam, data on restored of ions into saliva.32,33 Our analysis examined only wear (attrition and tooth surfaces, body weight and age were drawn directly from data abrasion) as a means of exposure. Reported rates of wear of Au alloy and available from 2001 through 2004 NHANES. The 2001–2004 NHANES were ceramic dental materials are summarized in Table 3 and Table 4, the latest surveys in which detailed data on oral health was collected. In a respectively. representative subset of the US population aged 24 months and older, Exposure estimates owing to dental material wear (attrition, abrasion), data were recorded on the presence/absence of dental restorations on for different material components, were derived as a function of the each tooth surface (lingual, facial, mesial, distal and occlusal) of every tooth volume loss of material during wear, combined with the density of that of each survey participant. Later NHANES recorded insufﬁcient detail on material and the relative percent composition of the different components dental health to permit their use in this risk assessment. The data from in those materials. Exposure to components of Au alloy and ceramic 2001–2002 and 2003–2004 were merged, as recommended for NHANES,31 restorations will occur only by ingestion, as components of these dental to increase overall sample size. materials are non-volatile.

Table 3. Summary of in vitro studies on rates of wear for gold alloy dental restorations and materials.

Wear (μm unless otherwise noted)

Reference % Au in alloy tested Mean Range Duration (cycles) Wear type Wear rate

76 51.5 0.32 ± 0.1 10,000 2 Bodya 0.022 μm/day 32 71 16.28 ± 5.59 25,000 2 Body 0.44 μm/day 77 46 0.152 ± 0.055 100,000 2 Body 1.04 μm 78 85.8 51 200,000 3 Bodyb 0.175 μm/day 79 75c 0.2 (generalized)/13.8 (localized) ± 0.1/± 5.0 100,000 3 Body 0.0007 μm/day/0.05 μm/day 80d 70 0.55 mm3 50,000 2 Body 116 μg/daye 57 70 12.8 ± 1.6) 11.8–16 100,000 3 Body 0.088 μm/day 81f 56 22 250,000 2 Body 0.06 μm/day 0.021 mm3 250,000 0.8 μg/dayg aFor 2 body wear, 250,000 cycles equivalent to 1 year.82 bFor 3 body wear, 400,000 cycles equivalent to 3 years.83 cNot reported by authors; based on common composition of Type III casting alloys. dWear rate based on volume loss; density of gold alloy reported by authors as 15.4 mg/mm3. eDerived as volume lost (mm3) × density (mg/mm3) × 250,000 (cycles/year)/50,000 (cycles)/365 (days/year) × 1000 (μg/mg). fDensity reported by authors as 13.9 mg/mm3. gDerived as volume lost (mm3) × density (mg/mm3) × 250,000 (cycles/year)/250,000 (cycles)/365 (days/year) × 1000 (μg/mg)

Table 4. Summary of in vitro studies on rates of wear for ceramic dental restorations and materials.

Wear (μm unless otherwise noted)

Reference Ceramic type Mean Range Duration (cycles) Wear type Wear rate μm/day

32 Alpha porcelain 76.04 ± 12.39 25,000 2 Bodya 2.08 Omega porcelain 62.02 ± 20.85 25,000 2 Bodya 1.7 Duceram-LFC 41.88 ± 17.36 25,000 2 Bodya 1.15 84 Alpha porcelain 30 25,000 2 Bodya 1.31 Omega porcelain 43 25,000 3 Bodyb 1.88 Duceram-LFC 11 25,000 3 Bodyb 0.48 82 Ceramco II 157 ± 22 500,000 NAc 0.22 76 Procera all-ceramic porcelain 4.3 ± 2.3 10,000 2 Bodya 0.3 85 Dicor (glass ceramic) 59 ± 37.9 1,200,000b NAd 0.03 Biodent (feldspathic porcelain) 51.3 ± 19.2 1,200,000 NAd 0.03 IPS/empress (glass ceramic) 21.8 ± 8.8 1,200,000 NAd 0.01 IPS/empress (glass ceramic) 36.2 ± 13.2 1,200,000 NAd 0.02 86 Dicor MGC light 0.249 mm ± 0.044 100,000 2 Bodya 1.71 IPS empress 0.093 mm ± 0.032 100,000 2 Bodya 0.64 Vita mark I1 block 0.069 mm ± 0.018 100,000 2 Bodya 0.47 Midas 0.152 mm ± 0.055 100,000 2 Bodya 1.04 Abbreviation: NA, not applicable. aFor two-body wear, 250,000 cycles equivalent to 1 year.82 bFor three-body wear, 400,000 cycles equivalent to 3 years.83 c500,000 cycles equivalent to 2 years.84 d1,200,000 cycles equivalent to 5 years.85

To estimate chronic daily dose owing to physical wear (attrition+abrasion) for ceramic between 0.01 μm/day and 2 μm/day), with any value between of Au alloy and ceramic dental materials, the following equation was used: these limits being equally likely. For Au alloys, no pattern of increasing Xn or decreasing wear rate with increasing Au content was observed in the SAi ´ WRi ´ Di ´ PCj WearDosej ¼ ð1Þ compiled data. i - 1 BW The wear rate for non-occlusal surfaces (due to abrasion only) is less than that for occlusal surfaces. Non-occlusal surfaces have no attrition where Wear Dosej = the daily intake of component j due to physical wear 34 fi from tooth surfaces i through n, where n is the total number of restored during mastication, but will still be subject to abrasion. Data speci cally surfaces per individual (μg/kg-day), n = number of tooth surfaces identified as on abrasion loss from non-occlusal Au alloy or ceramic surfaces was not available. Therefore, it was assumed that the rate of wear of non-occlusal containing a dental restoration; SAi = surface area of restoration on tooth surface i (mm2); i = 1 to n, where n is the total number of restored tooth Au alloy and ceramic surfaces would be equivalent to that of contact-free surfaces per individual, WRi = the wear rate (height loss) of restoration on occlusal surfaces. This ranges from 25% to 76% of the wear rate for occlusal tooth surface i (mm/day); different values for WR were applied for occlusal surfaces with opposing teeth.34 Values for non-occulsal surface wear were versus non-occlusal surfaces as explained below; Di = density of restorative assigned randomly for both dental materials, with any value between the 3 material used to restore tooth surface i (μg/mm ); values for Di presented in minimum and maximum deemed equally likely. Table 1; BW = body weight (kg); measured individually for each NHANES participant. The NHANES dental health data recorded the precise tooth and tooth Surface Area of Dental Restorations surface containing restorations, permitting distinction between occlusal When considering crowns (five surface restorations on molars and pre- and non-occlusal surfaces. For occlusal restorations, each participant molars; four surface restorations on non-molar teeth), the entire surface of record within the NHANES data set was assigned a wear rate for occlusal the subject tooth was assumed to be completely covered by the Au alloy (or ceramic) restorations selected randomly between the restoration. In this case, each occlusal and non-occlusal surface was minimum and maximum value (for Au between 0.02 μm/day and 1 μm/day; assumed to be 90 mm2 in area.35 For restorations other than crowns, the

Table 5. Total US adult population with dental restorations expected to exceed RELs for identiﬁed components, and numbers of restorations that prevent REL exceedence.

Dental material Component Scenario 1 Scenario 2 Scenario 3 Safe number of restored Safe number of restored tooth surfaces (N)a teeth (N)b

N (millions)4REL N (millions)4REL N (millions)4REL

Au alloy Au NAc NA NA NA NA Ag 98.71 55.16 5.91 4 2 Cu 1.06 0.19 0 No limitd No limite Zn 0 0 0 No limit No limit Pd 67.76 35.38 1.54 10 4 Pt 74.61 41.75 2.90 7 3 In 7.41 2.47 0 87 No limit

Ceramic Si 0 0 0 No limit No limit Al 0 0 0 No limit No limit Mg 0 0 0 No limit No limit Ti 0 0 0 No limit No limit Sn 0 0 0 No limit No limit Zn 0 0 0 No limit No limit Ba 0 0 0 No limit No limit Li 54.41 27.85 0.88 15 6 B 0 0 0 No limit No limit Amalgamf Hg0 148.4 143.7 100.8 1.7 1 Composite resinsg BPA 0 0 0 No limit No limit Abbrreviations: NA, not applicable; REL, reference exposure level. aValues rounded to nearest whole number. Derived assuming: average adult body weight = 80 kg (from NHANES data); median rates of wear (Au alloys, 0.5 μm/day; ceramics, 1 μm/day); median proportional composition for “typical range” for each component element from Table 1; median surface area of restorations (45 mm2); 15,000 μg/mm3 density for Au restorations and 2500 μg/mm3 density for ceramic restorations. bAssumes an average of 2.5 ﬁlled surfaces per ﬁlled tooth (as per NHANES data); values rounded to nearest whole number. cNot applicable; no REL available for gold. dExceeds maximum number of possible surfaces (N4128). eExceeds maximum possible number of teeth (N432). fData on amalgam from Richardson et al.4 added for comparison. Safe number of restored surfaces based on Canadian REL-equivalent dose from Richardson et al.87 owing to dated nature of USEPA REL (see Richardson et al.87 for discussion). gData on composite resins from Richardson et al.8 added for comparison. Safe number of restored surfaces based on lowest published REL for BPA of 16 μg/kg-day;88 the USEPA reference dose is 50 μg/kg-day.89

minimum size per surface was assumed to be 4 mm2, and the maximum Au or all ceramic restorations. In the only report quantifying the relative size was assumed to be 90 mm2. The surface area of restorations on occurrence of Au alloys versus other restorative materials for a segment specific tooth surfaces was assigned randomly, with any surface area of the US adult population,37 10.7% of in-place restorations were between these values being equally likely. composed of Au alloy. Proportional use for combined porcelain, cement or temporary restorations (including glass ionomer restorations and the porcelain surfaces of porcelain-fused-to-metal crowns),37 indicated the The Proportion of Persons and Tooth Surfaces with Au or Ceramic same assumption of 11% was also appropriate for ceramics. Restorations Exposure to any component of any specific dental material only occurs from tooth surfaces restored with that material. Therefore, it is appropriate to discount the numbers of individuals with no Au alloy or no ceramic Estimating Allowable Restorations of Au Alloy or Ceramic Material restorations, and also to discount tooth surfaces restored with any and all Based on Chemical Risk other dental materials. Unfortunately, the 2001–2004 NHANES surveys did Whereas dose can be derived using Equation 1 above, a defined “safe” not record the composition of the dental restorative materials present on reference exposure level (REL; also known as reference dose, tolerable daily filled tooth surfaces of survey participants, so information was necessarily intake and so on) can be substituted for dose and the equation can be compiled from other sources. reversed to solve for the number (N)offilled tooth surfaces that will not Reports and literature concerning the relative use of different dental result in exceeding the REL. The assumptions used to solve for N are materials in the US and Canada have been reviewed in detail elsewhere,4 summarized in footnotes to Table 5. and will not be repeated here. To be consistent with the assessment of exposure and risks associated with dental amalgam, the assessment of RELs for Components of Au Alloy and Ceramic Dental Materials exposure of adults to components of Au alloy and ceramic restorations was Available RELs are presented in Table 1. Preference was given to those RELs approached independently for each material, in three scenarios: published by the US Environmental Protection Agency (USEPA). Alternate sources were used when the USEPA had no current RELs available on its ● All dental restorations were assumed to be composed of Au alloy or integrated risk information system, or from EPA Regions 3 or 9. ceramic. ● Only crowns (five surface fillings of molars and premolars; four surface fillings of non-molar teeth) were considered to be composed of Au alloy RESULTS or ceramic. All other tooth surfaces were assumed to be restored with fi other materials. The exposure estimates presented in Table 6 are the rst publi- ● Only 30% of persons with dental restorations were assumed to have at shed population-based estimates of exposures to components of least one Au or one ceramic restoration and, for this group, 11% of all Au alloy and ceramic dental restorations. Exposure statistics restored tooth surfaces contained either Au alloy or ceramic. For this (mean, percentiles) were derived on the basis of the US adult latter scenario, ~ 30% of dentists in the US are amalgam free,36 population considered in each exposure scenario (indicated in suggesting that their patients might have a pre-disposition to having all Table 6), not on the total NHANES sample population.

Table 6. Doses (arithmetic mean ± standard deviation (5th–95th percentile; maximum)) of components of Au alloy and ceramic dental restorations in the US adult population.

Scenarioa 123

Population in scenariob 151,299,412 76,675,777 45,331,121

Material Component Dose (μg/kg-day) Dose (μg/kg-day) Dose (μg/kg-day)

Au alloy Au 68.5 ± 102.8 61.4 ± 76.0 7.3 ± 9.0 (1.41–265.70; 1896.6) (3.60–227.52; 733.5) (0.30–26.33; 75.2) Ag 22.1 ± 34.1 19.5 ± 25.9 2.3 ± 3.0 (0.45–87.87; 492.4) (1.03–65.81; 280.8) (0.09–8.77; 24.8) Cu 11.8 ± 18.7 10.7 ± 14.4 1.3 ± 1.7 (0.23–46.85; 265.5) (0.58–38.22; 160.0) (0.04–4.71; 14.4) Zn 1.3 ± 2.7 1.1 ± 2.0 0.1 ± 0.2 (0–5.97; 50.1) (0–4.54; 31.5) (0–0.59; 2.0) Pd 4.1 ± 7.5 3.7 ± 5.7 0.4 ± 0.7 (0.06–16.65; 133.7) (0.14–13.97; 70.2) (0.01–1.69; 9.2) Pt 7.3 ± 13.3 6.6 ± 10.4 0.8 ± 1.2 (0.1–31.29; 261.6) (0.18–26.57; 125.5) (0.02–3.12; 13.9) In 1.9 ± 3.7 1.7 ± 2.8 0.2 ± 0.3 (0.01–8.14; 97.5) (0.03–6.55; 35.7) (0.002–0.80; 3.1) Ceramic Si 23.2 ± 33.4 21.6 ± 27.0 2.4 ± 3.0 (0.52–91.19; 384.3) (1.06–71.41; 263.3) (0.09–9.12; 25.0) Al 5.8 ± 9.4 5.4 ± 7.1 0.6 ± 0.8 (0.11–22.06; 116.0) (0.24–19.10; 78.4) (0.02–2.32; 8.0) Mg 0.9 ± 1.7 0.8 ± 1.5 0.1 ± 0.2 (0–3.84; 33.1) (0–3.42; 17.9) (0–0.35; 1.7) Ti 0.5 ± 1.1 0.5 ± 0.9 0.1 ± 0.1 (0–2.34; 17.7) (0–2.07; 11.2) (0–0.33; 1.2) Sn 0.9 ± 1.8 0.8 ± 1.4 0.1 ± 0.2 (0–3.85; 33.1) (0–3.28; 15.4) (0–0.39; 1.6) Zn 1.4 ± 2.7 1.3 ± 2.1 0.1 ± 0.2 (0–5.99; 32.8) (0–5.25; 23.3) (0–0.61; 2.7) Ba 0.4 ± 0.9 0.3 ± 0.7 0.04 ± 0.07 (0–1.63; 16.6) (0–1.47; 7.5) (0–0.17; 0.8) Li 3.0 ± 5.5 2.7 ± 4.1 0.3 ± 0.5 (0.002–12.35; 93.6) (0–10.53; 44.5) (0–1.26; 6.1) B 1.2 ± 2.5 1.2 ± 1.9 0.1 ±0.2 (0–5.25; 47.6) (0–4.44; 21.6) (0–0.55; 1.9) aScenario 1, all ﬁllings are Au alloys or ceramics; Scenario 2, all full tooth crowns of Au or ceramics; Scenario 3, 30% of persons with restorations have Au alloy or ceramic restorations, with 11% of existing restorations as Au or ceramic. bPopulation sizes include persons with at least one restored tooth.

Table 5 presents estimated numbers of filled tooth surfaces for 2.9 million adults would exceed the REL for Pt and 1.5 million each restorative material that should not result in exceeding RELs adults would exceed the REL for Pd (Table 5; Figure 1). These two for their component elements. elements have the highest relative toxicity (lowest RELs) of Au alloy components. Cu and In present no exceedences of their RELs Au Alloys for the third, most realistic, exposure scenario. Zn is the component of least concern with no exposures exceeding the The relatively high Ag content of dental Au alloys, combined with REL for Zn in any of the three scenarios considered here. Ag’s relatively low REL (high-relative toxicity; Table 1), results in Ag Au has the highest relative composition of all the components being the most problematic component (Figure 1). Assuming that in Au alloys but no REL is available for inorganic Au from any all dental restorations in the US population were composed of Au national or international agency. Organo-Au compounds are alloys (Scenario 1) would result in a significant number of US known to be toxic,38 but no mammalian toxicological data are adults (98.7 million persons) receiving a dose that exceeds the available for inorganic Au compounds. The release of Au from reference dose for Ag. Such a situation would be extremely dental Au alloys leads to a relatively high incidence of allergic unlikely; however, the most realistic exposure scenario (Scenario 3) sensitivity, perhaps as high as 23% of those with Au restorations.39 still suggests that the exposure received by some 5.9 million – Au from dental alloys is excreted in urine,40 42 and reaches the adults with Au alloy dental restorations would exceed the blood,16 in concentrations proportional to dental Au load. Further reference dose for Ag published by the USEPA. research is required to establish an oral REL for inorganic Au, to Exposure to metals released from Au alloys is such that the permit a quantitative assessment of potential risks posed by number of Au alloy restorations that can be present and not exposure to this component of Au dental alloys. exceed respective RELs, is limited. For Ag, it was estimated that only four filled surfaces (or two restored teeth) would result in a dose equivalent to the REL for this element (Table 5). Ceramics Pt and Pd in Au alloy restorations also present some risk to the Li is more toxic than the other ceramic components (Table 1). This, US population. Even with the most realistic scenario (Scenario 3), combined with the Li content of some ceramic materials (range up

Figure 1. Range (5th–95th percentile) and mean exposures to Ag, Pd and Pt from Au alloy dental materials, and Li from ceramic dental materials. Exposure scenarios described in the text. Horizontal bar represents the reference exposure level for each element. Percentile and mean exposure doses as reported in Table 6.

to 19% by weight), results in Li exposures exceeding its REL to Comparisons with Amalgam and Composite Resin some extent in all scenarios (Table 5; Figure 1). For the most The estimates of exposure and risk presented herein have been realistic Scenario 3, the REL could be exceeded in some 880,000 derived in a manner that permits direct comparison with esti- US adults with ceramic dental restorations. Exposures to com- mated mercury vapor (Hg0) exposures from dental amalgam,4 as ponents other than Li are much less compared with their well as components and degradation products of composite resin respective RELs, even when it is assumed that all dental dental restorations.7,8 Figure 2 presents information comparable restorations in the adult population are composed of ceramics to Figure 1, but for exposure to Hg0 from dental amalgam, and (see Scenario 1, Table 6 and Table 5). If the Li content of ceramics exposure to BPA from composite resins. Table 5 also includes ≤ is 0.5% by weight, estimates of maximum Li exposure are greatly numbers of filled tooth surfaces for dental amalgam and com- reduced, and no limits on the number of ceramic restorations posite resins that should not result in exceeding RELs for their would be evident. component elements or substances, for direct comparison to Au The estimated exposures to Li from ceramic restorations are alloys and ceramics. Based on review of Figures 1 and 2, and conservative as they represent total ingestion exposures, and not Table 5, relative risks of chemical exposures from dental materials systemically absorbed doses. Soluble Li compounds are readily 4 4 4 43,44 compare as follows: Dental amalgam Au alloy ceramics com- absorbed from the gastrointestinal tract. There is evidence posite resins. that Li can solubilize from ceramic materials,26,45 so some of the Li in the abraded and ingested ceramic particles will be solubilized in the gastrointestinal tract. However, this solubility will likely be DISCUSSION o 100% of available Li. Future investigation of the gastrointestinal There are no regulatory requirements for premarket exposure and solubility of Li from ceramics is warranted. risk assessment of dental restorative materials in the US, Canada or elsewhere. As a result, regulatory agencies facing challenges Leaching of Metals from Au Alloy and Ceramic Dental Restorations to dental material safety undertake ad hoc and inconsistent Leaching of ions from Au alloy and ceramic restorations was approaches to resolve criticisms, typically with no supporting omitted from our analysis. Metal ions have been observed in the quantitative exposure and risk analysis.2,47,48 Quantitative exposure saliva of dental patients with these restorations;15,41,42,46 however, and risk assessment should be a component of that evaluation levels in saliva will be a combination of loss owing to both process, but cannot be the only consideration. Research is leaching and wear. A preliminary analysis (computations not published routinely on the efficacy of dental materials (leaching, shown) suggests that the contribution of leaching to exposure clinical performance, longevity, recurrent decay and so on). may be low (o15%), relative to dental material wear. However, an However, a standard, routine, systematic and quantitative assessment should be undertaken to quantify exposure specifi- approach to the evaluation of the relative efficacy, benefits, cally because of leaching, to complement the analysis on material exposures and risks is needed for all dental materials, particularly wear presented herein. given the 130 million dental restorations that are placed annually

Figure 2. Range (minimum–maximum) and mean exposures to Hg0 from dental amalgam,4 and BPA from composite resins,8 for comparison with Figure 1. Exposure scenarios are comparable to those for Au alloy and ceramics; see references for details. For composite resins, only Scenario 3 (all ﬁllings as composite resins) is considered, owing to no exceedance of published reference exposure levels (RELs). Horizontal bar represents the REL for each substance.

1 in the US population. This information should be critically 10 Zimmerman-Downs JM, Shuman D, Stull SC, Ratzlaff RE. Bisphenol A blood and evaluated, and publically available, to help dental clinicians, in saliva levels prior to and after dental sealant placement in adults. J Dent Hyg 2010; consultation with their patients, determine which restorative 184:145–150. materials are optimum for use. 11 Nicolae A, An Analysis of the Relationship between Urinary Mercury Levels and the Number of Dental Amalgam Restoration Surfaces in a Representative Group of the Canadian Population. Report prepared in association with the program on Dental Public Health, University of Toronto, Toronto, ON, Canada. Dated Summer/ CONFLICT OF INTEREST Fall 2010. The authors declare no conflict of interest. 12 Vidnes-Kopperud S, Tveit AB, Gaarden T, Sandvik L, Espelid I. Factors influencing dentists’ choice of amalgam and tooth-colored restorative materials for Class II preparations in younger patients. Acta Odontol Scand 2009; 67:74–79. ACKNOWLEDGMENTS 13 Tran LA, Messer LB. Clinicians’ choices of restorative materials for children. Austral Dent J 2003; 48: 221–232. Funding for this project was provided by the Natural Sciences and Engineering 14 Peretz B, Ram D. Restorative material for children's teeth: preferences of parents Research Council of Canada, Collaborative Research and Training Experience and children. ASDC J Dent Child 2002; 69: 233. (CREATE) Grant in Human and Ecological Risk Assessment (HERA), to SDS and GMR. 15 Elshahawy W, Ajlouni R, James W, Abdellatif H, Watanabe I. Elemental ion release Funding in kind, for time committed by GMR and SRC, was provided, respectively, by from fixed restorative materials into patient saliva. JOralRehabil2013; 40:381–385. Stantec Consulting, and SNC-Lavalin Environment, both of Ottawa, Ontario, Canada. 16 Ahlgren C, Molin M, Lundh T, Nilner K. Levels of gold in plasma after dental gold inlay insertion. Acta Odontol Scand 2007; 65: 331–334. 17 ADA (American Dental Association). Practical science: direct and indirect REFERENCES restorative materials. J Am Dent Assoc 2003; 134:463–472. 18 Donaldson JA. The use of gold in dentistry: an historical overview, part 1. Gold Bull 1 Beazoglou T, Eklund S, Heffley D, Meiers J, Brown LJ, Bailit H. Economic impact of 1980; 13: 117–124. regulating the use of amalgam restorations. Public Health Rep 2007; 122:657–663. 19 Donaldson JA. The use of gold in dentistry: an historical overview, part 2. Gold Bull 2 USFDA (US Food and Drug Administration). White Paper: FDA Update/Review of 1980; 13: 160–165. Potential Adverse Health Risks Associated with Exposure to Mercury in Dental 20 Christensen G J. Longevity versus esthetics: the great restorative debate. JAm Amalgam. National Center for Toxicological Research, USFDA: Washington, DC, Dent Assoc 2007; 138: 1013–1015. 2009. 21 Knosp H, Holliday RJ, Corti CW. Gold in dentistry: alloys, uses and performance. 3 Richardson GM. Mercury exposure and risks from dental amalgam in Canada: the Gold Bull 2003; 36:93–101. – 20 Canadian Health Measures Survey 2007 2009. Hum Ecol Risk Assess 2014; : 22 ADA (American Dental Association). Grills, ‘grillz’ and fronts. J Am Dent Assoc 2006; – 433 447. 137: 1192. 4 Richardson GM, Wilson R, Allard D, Purtill C, Douma S, Gravière J. Mercury 23 Leinfelder KF. An evaluation of casting alloys used for restorative procedures. exposure and risks from dental amalgam in the US population, post-2000. J Am Dent Assoc 1997; 128:37–45. 409 – Sci Total Environ 2011; : 4257 4268. 24 Chu S, Ahmad I. A historical perspective of synthetic ceramic and traditional 5 Richardson GM. Inhalation of mercury-contaminated particulate matter by den- feldspathic porcelain. Pract Proced Aesthet Dent 2005; 17:593–598. 9 – tists: an overlooked occupational risk. Hum Ecol Risk Assess 2003; : 1519 1531. 25 Jones DW. A brief overview of dental ceramics. J Can Dent Assoc 1998; 64: 6 Richardson GM, Evidence that bisphenol-a exposure is not associated with 648–650. composite resin dental fillings. E-Letter, PediatricsOnline at http://pediatrics.aap 26 Kukiattrakoon B, Hengtrakool C, Kedjarune-Leggat U. The effect of acidic agents publications.org/content/130/2/e328/reply. Published August 21 2012. on surface ion leaching and surface characteristics of dental porcelains. J Prosthet 7 Richardson GM. Assessment of adult exposure and risks from components and Dent 2010; 103:148–162. degradation products of composite resin dental materials. Hum Ecol Risk Assess 27 Christensen GJ. The coming demise of the cast gold restoration? J Am Dent Assoc 1997; 3: 683–697. 1996; 127:1233–1236. 8 Richardson GM, Clark KE, Williams DR. Preliminary estimates of adult exposure to 28 Mormann WH. The evolution of the CEREC system. J Am Dent Assoc 2006; 137: bisphenol-a from dental materials, food and ambient air. In: Henshel DS, Black MC, 7S–13S. Harrass MC (eds). Environmental Toxicology and Risk Assessment: Standardization of 29 Eley BM. The future of dental amalgam: a review of the literature. Part 7: possible Biomarkers for Endocrine Disruption and Environmental Assessment: Eighth Volume, alternative materials to amalgam for the restoration of posterior teeth. Br Dent J American Society for Testing and Materials: West Conshohocken, PA, 1999 1997; 183:11–14. pp 286–301. 30 USEPA (US Environmental Protection Agency). Risk Assessment Guidance for 9 Joskow R, Barr DB, Barr JR, Calafat AM, Needham LL, Rubin C. Exposure to Superfund: Volume III - Part A, Process for Conducting Probabilistic Risk Assessment bisphenol A from bis-glycidyl dimethacrylate-based dental sealants. J Am Dent Report EPA 540-R-02-002.Office of Emergency and Remedial Response, USEPA: Assoc 2006; 137: 353–362. Washington, DC, 2001.

Journal of Exposure Science and Environmental Epidemiology (2016), 70 – 77 © 2016 Nature America, Inc. Exposures from gold and ceramic dental materials Richardson et al 77 31 NCHS (National Center for Health Statistics). Analytic and Reporting Guidelines: The 61 USEPA (US Environmental Protection Agency). Integrated Risk Information System National Health and Nutrition Examination Survey (NHANES). Centers for Disease (IRIS). Online at http://www.epa.gov/iris/. Accessed on 15 December 2013. Control and Prevention: Hyattsville, Maryland, 2005. 62 Health Canada. Federal Contaminated Site Risk Assessment in Canada Part II: Health 32 Al-Hiyasat AS, Saunders WP, Sharkey SW, Smith GM, Gilmour WH. Investigation of Canada Toxicological Reference Values (TRVs) and Chemical-Specific Factors, Version human enamel wear against four dental ceramics and gold. JDent1998; 26:487–495. 20. Contaminated Sites Division, Health Canada: Ottawa, ON, Canada, 2010. 33 Yip KH-K, Smales RJ, Kaidonis JA. Differential wear of teeth and restorative 63 EMA (European Medicines Agency). Guideline on the specification limits for residues materials: clinical implications. Int J Prosthodon 2004; 17:350–356. of metal catalysts, Doc. Ref. CPMP/SWP/QWP/4446/00 corr Committee for Human 34 Willems G, Lambrechts P, Braem M, Vanherle G, Classification and wear of dental Medicinal Products, EMA: London, UK, 2007. composites. Proc. Int. Symp. on State-of-the-art on Direct Posterior Filling 64 Moskowitz PD, Bernholc N, DePhillips MP, Viren J Derived reference doses for three Materials and Dentin Bonding, Paris 1993. compounds used in the photovoltaics industry: copper indium diselenide, copper 35 Kraus B S, Jordan R E, Abrams L Dental Anatomy and Occlusion. Williams and gallium diselenide, and cadium telleride Report BNL-62045. Biomedical and Envir- Wilkins, Co: Baltimore, MD, 1978. onmental Assessment Group, Analytical Sciences Division, Department of Applied 36 Haj-Ali R, Walker M P, Williams K. Survey of general dentists regarding posterior Science, Brookhaven National Laboratory: Long Island, NY, Dated July 6 1995. restorations, selection criteria, and associated clinical problems. Gen Dent 2005; 65 Anusavice KJ. Degradability of dental ceramics. Adv Dent Res 1992; 6:82–89. 53: 369–375. 66 Elmaria A, Goldstein G, Vijayaraghavan T, Legeros RZ, Hittelman EL. An evaluation 37 Albertini T F, Kingman A, Brown J. Prevalence and distribution of dental of wear when enamel is opposed by various ceramic materials and gold. restorative materials in US air force veterans. J Public Health Dent 1997; 57:5–10. J Prosthet Dent 2006; 96: 345–353. 38 Kean WF, Kean IRL. Clinical pharmacology of gold. Inflammopharmacology 2008; 67 Jakovac M, Zivko-Babic J, Curkovic L, Aurer A. Measurement of ion elution from 26 – 16: 112–125. dental ceramics. J Europ Ceram Soc 2006; : 1695 1700. 39 Eisler R. Mammalian sensitivity to elemental gold (Au0). Biol Trace Elem Res 2004; 68 Kase HR, Tesk JA, Case ED. Elastic constants of two dental porcelains. J Mater Sci 20 – 100:1–17. 1985; :524 531. – 40 Benemann J, Lehmann N, Bromen K, Marr A, Seiwert M, Schulz C, Jockel K-H. 69 Roy S, Basu B. Hardness properties and microscopic investigation of crack crystal – – – – – Assessing contamination paths of the German adult population with gold and interaction in SiO2 MgO Al2O3 K2O B2O3 F glass ceramic system. J Mater Sci 21 – platinum. The German Environmental Survey 1998 (GerES III). Int J Hyg Environ Mater Med 2010; :109 122. Health 2005; 208: 499–508. 70 Santos C, Souza RC, Almeida N, Almeida FA, Silva RRF, Fernandes MHFV. Tough- 41 Schierl R. Urinary platinum levels associated with dental gold alloys. Arch Environ ened ZrO2 ceramics sintered with a La2O3-rich glass as additive. J Mater Process 200 – Health 2001; 56: 283–286. Technol 2008; :126 132. 42 Drasch G,; Muss C, Roider G. Gold and palladium burden from dental restoration 71 Uo M, Sjoren G, Sundh A, Watari F, Bergman M, Lerner U. Cytotoxicity and 19 – materials. J Trace Elem Med Biol 2000; 14:71–75. bonding property of dental ceramics. Dent Mater 2003; :487 492. 43 Schrauzer GN. Lithium: occurrence, dietary intakes, nutritional essentiality. JAm 72 Zhang Y, Kim J-W. Graded structures for damage resistant and aesthetic all-ceramic restorations. Dent Mater 2009; 25:781–790. Coll Nutr 2002; 21:14–21. 73 UKEGVM (UK Expert Group on Vitamins and Minerals). Safe Upper Levels for 44 Shiotsuki I, Terao T, Ogami H, Ishii N, Yoshimura R, Nakamura J. Drinking spring water Vitamins and Minerals. UKEGVM, Committee on Toxicology, Food Standards and lithium absorption: a preliminary study. Ger J Psychiatry 2008; 11:103–106. Agency: UK, 2003. 45 Milleding P, Haraldsson C, Karlsson S. Ion leaching from dental ceramics during 74 USEPA (US Environmental Protection Agency). Regional Screening Level (RSL) static in vitro corrosion testing. J Biomed Mater Res 2002; 61:541–550. Summary Table. USEPA, Region 3. Online at http://www.epa.gov/reg3hwmd/risk/ 46 Garhammer P, Hiller KA, Reitinger T, Schmalz G. Metal content of saliva of patients human/rb-concentration_table/Generic_Tables/ index.htm. Accessed 15 Decem- with and without metal restorations. Clin Oral Investig 2004; 8: 238–242. ber 2013. 47 CADTH (Canadian Agency for Drugs and Technologies in Health). Composite Resin 75 NVDEP (Nevada Division of Environmental Protection). Technical memorandum: and Amalgam Dental Filling Materials: A Review of Safety, Clinical Effectiveness and Toxicity Criteria for Titanium and Compounds, and for Tungsten and Compounds. Cost-effectiveness. CADTH: Ottawa, Canada, 2012. Nevada State Department of Conservation and Natural Resources, 2008. 48 SCENIHR (Scientific Committee on Emerging and Newly-Identified Health Risks). 76 Hacker CH, Wagner WC, Razzoog ME. An in vitro investigation of the wear of Scientific opinion on the Safety of Dental Amalgam and Alternative Dental enamel on porcelain and gold in saliva. J Prosthet Dent 1996; 75:14–17. Restoration Materials for Patients and Users. Health and Consumer Protection 77 Ramp MH, Suzuki S, Cox CF, Lacefield WR, Koth DL. Evaluation of wear: enamel Directorate-General, European Commission: Brussels, 2008. opposing three ceramic materials and a gold alloy. J Prosthet Dent 1997; 77: 49 Begerow J, Neuendorf J, Turfeld M, Raab W, Dunemann L. Long-term urinary 523–530. platinum, palladium, and gold excretion of patients after insertion of noble-metal 78 Graf K, Johnson GH, Mehl A, Rammelsberg P. The influence of dental alloys on 4 – dental alloys. Biomarkers 1999; :27 36. three-body wear of human enamel and dentin in an inlay-like situation. Oper Dent 50 Lopez-Alias J F, Martinez-Gomis J, Anglada J M, Peraire M. Ion release from dental 2002; 27:167–174. fl casting alloys as assessed by a continuous ow system: nutritional and tox- 79 Suzuki S, Nagai E, Taira Y, Minesaki Y. In vitro wear of indirect composite 22 – icological implications. Dent Mater 2006; : 832 837. restoratives. J Prosthet Dent 2002; 88: 431–436. 51 Sjogren G, Sletten G, Dahl JE. Cytotoxicity of dental alloys, metals, and ceramics 80 Ohkubo C, Shimura I, Aoki T, Hanatani S, Hosoi T, Hattori M, Oda Y, Okabe T. Wear fi 84 assessed by millipore lter, agar overlay, and MTT tests. J Prosthet Dent 2000; : resistance of experimental Ti-Cu alloys. Biomaterials 2003; 24: 3377–3381. – 229 236. 81 Alarcon JV, Engelmeier RL, Powers JM, Triolo. PT. Wear testing of composite, gold, 52 Wataha JC, Lockwood PE. Release of elements from dental casting alloys into cell- porcelain, and enamel opposing a removable cobalt–chromium partial 14 – culture medium over 10 months. Dent Mater 1998; :158 163. denture alloy. J Prosthodont 2009; 18: 421–426. fi 53 Elshahawy W, Watanabe I, Koike M. Elemental ion release from four different xed 82 Delong R, Douglas WH, Sakaguchi RL, Pintado MR. The wear of dental porcelain in 25 – prosthodontic materials. Dent Mater 2009; : 976 981. an artificial mouth. Dent Mater 1986; 2:214–219. – 54 Hero H, Jorgensen R, Sorbroden E. A low-gold dental alloy structure and segre- 83 Leinfelder KF, Suzuki S. In vitro wear device for determining posterior gations. J Dent Res 1982; 61: 1292–1298. composite wear. J Am Dent Assoc 1999; 130:1347–1353. 55 Johansson G, Bergman M, Anneroth G, Eskafi M. Human pulpal response to direct 84 Al-Hiyasat AS, Saunders WP, Smith GM. Three-body wear associated with three filling gold restorations. Scand J Dent Res 1993; 101:78–83. ceramics and enamel. J Prosthet Dent 1999; 82:476–481. 56 Lappalainen R, Yli-Urpo A. Release of elements from some gold-alloys and 85 Krejci I, Lutz F, Reimer M, Heinzmann JL. Wear of ceramic inlays, their enamel amalgams in corrosion. Scand J Dent Res 1987; 95:364–368. antagonists, and luting cements. J Prosthet Dent 1993; 69:425–430. 57 Ogino T, Koizumi H, Furuchi M, Murakami M, Matsumura H, Tanoue N. Effect of a 86 Ramp MH, Ramp LC, Suzuki S. Vertical height loss: an investigation of four metal priming agent on wear resistance of gold alloy-indirect composite joint. restorative materials opposing enamel. J Prosthodont 1999; 8:252–257. Dent Mater J 2007; 26:201–208. 87 Richardson GM, Brecher R, Scobie H, Hamblen J, Phillips K, Samuelian J, Smith C. 58 Ucar Y, Brantley WA, Johnston WM, Dasgupta T. Mechanical properties, fracture Mercury vapour (Hg0): continuing toxicological uncertainties, and establishing a surface characterization, and microstructural analysis of six noble dental Canadian reference exposure level. Regul Toxicol Pharmacol 2009; 53:32–38. casting alloys. J Prosthet Dent 2011; 105: 394–402. 88 Willhite CC, Ball GL, McLellan CJ. Derivation of a bisphenol A oral reference dose 59 Wataha JC. Alloys for prosthodontic restorations. J Prosthet Dent 2002; 87: (RfD) and drinking-water equivalent concentration.J Toxicol Environ Health B Crit 351–363. Rev 2008; 11:69–146. 60 Wataha JC, Lockwood PE, Khajotia SS, Turner R. Effect of pH on element release 89 USEPA (US Environmental Protection Agency). Integrated Risk Information System from dental casting alloys. J Prosthet Dent 1998; 80:691–698. (IRIS). Online at http://www.epa.gov/iris/. Accessed 7 January 2015.