Journal of Exposure Science and Environmental Epidemiology (2015), 1–8 © 2015 Nature America, Inc. All rights reserved 1559-0631/15

www.nature.com/jes

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 advance online publication, 25 March 2015; doi:10.1038/jes.2015.17 Keywords: dental materials; exposure; risk; gold; ceramics

INTRODUCTION One hundred and thirty million dental restorations are placed annually in the US population.1 Exposure to the components of dental materials occurs in people with dental fillings. Most attention has been focused on mercury from dental amalgam2–5 and to a lesser extent on bisphenol-a (BPA) from composite resins.6–10 However, no attention has yet been directed toward exposures to components of gold (Au) alloy or ceramic restorations, despite the rapid increase in preference for non-amalgam alternatives.1,11–14 Component elements of Au alloy and ceramic restorations have been observed in saliva at least 3 months after placement,15 and elevated levels in blood due to Au alloys 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 has amalgam,17–19 and are the preferred restorative materials of dental clinicians, particularly for their own teeth.20 Au alloys are primarily used as foils, inlays, onlays, crowns and dental wiring,21 but are also used as fashion jewelry (“grillz”) on teeth.22 Softer alloys are generally used for smaller single-surface preparations, whereas harder alloys are used for larger inlays, onlays and crowns.23 Dental ceramics have been used in dentistry since the 1800s,24 and are generally composed of feldspar porcelain, with newer formulations containing various alkali metals and other metal components to improve workability, strength and stiffness.25,26 They are used to produce inlays via external preparation from casts and molds of prepared cavities25,27 and, starting in the 1980s, employing computer aided design/computer aided

manufacturing technologies.28 Ceramics may also be used for veneers17 and be fused to a metal base for crowns and bridges.25 The overall rate of use of Au alloys and ceramics for dental restorations is relatively low, due to high cost,29 but their usage is increasing. US statistics in the mid-1990s indicated that o2% of all restorations placed were either Au alloy or ceramic.27 In 2005, they represented 21.8% of restorations placed.1 This paper presents the first estimates of exposure and potential risk from components of Au alloy and ceramic dental restorative materials. The work was undertaken in a manner consistent with that of a previous assessment of dental amalgam,4 in order to maximize the direct comparability of exposure and risk estimates.

METHODS Population-Level Assessment Population level, scenario-based chemical exposure and risk assessment requires use of probabilistic methods, such as Monte Carlo analysis.30 In this study, we combined the data from the NHANES (see NHANES Data section), including statistical weighting of survey participants, with other Monte Carlo methods to provide a more accurate extrapolation of exposure and risk to the entire US adult population.

Restorative Composition The Au content of Au dental alloys ranges widely,21 but typically ranges from 40% to 77% Au by weight.23 The other common components are silver (Ag), copper (Cu), indium (In), palladium (Pd), platinum (Pt) and zinc (Zn). Au alloy composition is summarized in Table 1.

1 Stantec 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

Exposures from gold and ceramic dental materials Richardson et al

2 Table 1.

Typical composition of gold alloy and ceramic dental restoratives, and component reference exposure levels. Minimum % composition

Maximum % composition

Most typical range % composition

Reference exposure level (μg/kg-day)

Au Ag Cu Pd Zn Pt In Density (g/cm3)

4.4 0 0 0 0 0 0 11.5

88.9 64.5 57 47.7 10 77.3 9 18.8

40–77 14–40 7.5–21 1–9 0–3 1–17 0–4.5 11.5–18.8

None available 5b 141c 2d 300b 2.6d 8.3e

SiO2 AlO2 MgO Li2O TiO2 SnO2 B2O3 BaO ZnO Density (g/cm3)

17 0 0 0 0 0 0 0 0 2.43

80 22 17 19 4.5 5.25 7 2 8 2.52

46–80 11–22 0–5 0–19 0–3 0–5 0–7 0–2 0–8 2.43–2.52

25,000g 1000h 6000g 2h 4000i 600h 200b 200b 300b

Dental Material

Component

Au alloya

Ceramicf

a

References 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 group Adults Seniors Survey totals US adult population represented

Age range (years)

Total survey sample size (N)

Number of participants with restored teeth

Average number of restored tooth surfacesa

Maximum number of restored surfaces

21–59b ≥ 60

5673 3151 8824 189,932,347

4454 2031 6485 151,299,412

17.9 28.9

128 109

a

Excludes 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 ceramics, typically constituting between 46% and 80% by weight. Other common components are oxides of aluminum (Al), magnesium (Mg), lithium (Li), titanium (Ti), tin (Sn), boron (B), barium (Ba) and zinc (Zn; see Table 1). For purposes of dose calculations, each participant record within the NHANES data set was assigned an Au content, or SiO2 content for ceramics, selected randomly between the minimum and maximum “most typical range” percent composition (Table 1). The percent compositions of all other components were then set randomly within their reported limits, but adjusted as necessary to ensure that total percent composition equated to 100%. This randomization procedure was deemed superior to a simple assumption that each participant be assigned the same composition, such as the maximum percent composition of Au, or Ag or other component.

NHANES Data Consistent with the assessment of dental amalgam,4 data on restored tooth surfaces, body weight and age were drawn directly from data available from 2001 through 2004 NHANES. The 2001–2004 NHANES were the latest surveys in which detailed data on oral health was collected. In a representative subset of the US population aged 24 months and older, data were recorded on the presence/absence of dental restorations on each tooth surface (lingual, facial, mesial, distal and occlusal) of every tooth of each survey participant. Later NHANES recorded insufficient detail on dental health to permit their use in this risk assessment. The data from 2001–2002 and 2003–2004 were merged, as recommended for NHANES,31 to increase overall sample size. Journal of Exposure Science and Environmental Epidemiology (2015), 1 – 8

Owing to the relatively high cost of both Au alloy and ceramic dental restorations, only adults (aged 21 years and older) were considered likely to possess these restorations. Adults represented 8824 survey participants from the NHANES data set (Table 2). NHANES also establishes the statistical weight of each participant. Therefore, the exposure estimate derived for each participant of the 2001– 2004 NHANES surveys was multiplied by their respective weighting factor to accurately adjust distributions of exposure to mirror the actual US adult population. Owing to survey merging, 4 year statistical weights were applied as recommended for NHANES.31 The total US adult population represented by the NHANES data set was 189,932,347.

Estimating Exposure Due to Wear Loss of material from a dental restoration into the oral cavity for 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; corrosion — chemical degradation of the restoration; and simple leaching of ions into saliva.32,33 Our analysis examined only wear (attrition and abrasion) as a means of exposure. Reported rates of wear of Au alloy and ceramic dental materials are summarized in Table 3 and Table 4, respectively. Exposure estimates owing to dental material wear (attrition, abrasion), for different material components, were derived as a function of the volume loss of material during wear, combined with the density of that material and the relative percent composition of the different components in those materials. Exposure to components of Au alloy and ceramic restorations will occur only by ingestion, as components of these dental materials are non-volatile. © 2015 Nature America, Inc.

Exposures from gold and ceramic dental materials Richardson et al

3 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

76 32 77 78 79 80d 57 81f

51.5 71 46 85.8 75c 70 70 56

Mean

Range

0.32 16.28 0.152 51 0.2 (generalized)/13.8 (localized) 0.55 mm3 12.8 ± 1.6) 22 0.021 mm3

± 0.1 ± 5.59 ± 0.055 ± 0.1/± 5.0 11.8–16

Duration (cycles) 10,000 25,000 100,000 200,000 100,000 50,000 100,000 250,000 250,000

Wear type a

2 Body 2 Body 2 Body 3 Bodyb 3 Body 2 Body 3 Body 2 Body

Wear rate 0.022 μm/day 0.44 μm/day 1.04 μm 0.175 μm/day 0.0007 μm/day/0.05 μm/day 116 μg/daye 0.088 μm/day 0.06 μm/day 0.8 μg/dayg

a

For 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 32 84 82 76 85

86

Ceramic type Alpha porcelain Omega porcelain Duceram-LFC Alpha porcelain Omega porcelain Duceram-LFC Ceramco II Procera all-ceramic porcelain Dicor (glass ceramic) Biodent (feldspathic porcelain) IPS/empress (glass ceramic) IPS/empress (glass ceramic) Dicor MGC light IPS empress Vita mark I1 block Midas

Mean

Range

76.04 62.02 41.88 30 43 11 157 4.3 59 51.3 21.8 36.2 0.249 mm 0.093 mm 0.069 mm 0.152 mm

± 12.39 ± 20.85 ± 17.36

± 22 ± 2.3 ± 37.9 ± 19.2 ± 8.8 ± 13.2 ± 0.044 ± 0.032 ± 0.018 ± 0.055

Duration (cycles) 25,000 25,000 25,000 25,000 25,000 25,000 500,000 10,000 1,200,000b 1,200,000 1,200,000 1,200,000 100,000 100,000 100,000 100,000

Wear type a

2 Body 2 Bodya 2 Bodya 2 Bodya 3 Bodyb 3 Bodyb NAc 2 Bodya NAd NAd NAd NAd 2 Bodya 2 Bodya 2 Bodya 2 Bodya

Wear rate μm/day 2.08 1.7 1.15 1.31 1.88 0.48 0.22 0.3 0.03 0.03 0.01 0.02 1.71 0.64 0.47 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 c 500,000 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) of Au alloy and ceramic dental materials, the following equation was used: WearDosej ¼

n X SAi ´ WRi ´ Di ´ PCj i-1

BW

ð1Þ

where Wear Dosej = the daily intake of component j due to physical wear from tooth surfaces i through n, where n is the total number of restored surfaces per individual (μg/kg-day), n = number of tooth surfaces identified as 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 surfaces per individual, WRi = the wear rate (height loss) of restoration on tooth surface i (mm/day); different values for WR were applied for occlusal versus non-occlusal surfaces as explained below; Di = density of restorative material used to restore tooth surface i (μg/mm3); values for Di presented in Table 1; BW = body weight (kg); measured individually for each NHANES participant. The NHANES dental health data recorded the precise tooth and tooth surface containing restorations, permitting distinction between occlusal and non-occlusal surfaces. For occlusal restorations, each participant record within the NHANES data set was assigned a wear rate for occlusal Au alloy (or ceramic) restorations selected randomly between the minimum and maximum value (for Au between 0.02 μm/day and 1 μm/day; © 2015 Nature America, Inc.

for ceramic between 0.01 μm/day and 2 μm/day), with any value between these limits being equally likely. For Au alloys, no pattern of increasing or decreasing wear rate with increasing Au content was observed in the compiled data. The wear rate for non-occlusal surfaces (due to abrasion only) is less than that for occlusal surfaces. Non-occlusal surfaces have no attrition during mastication,34 but will still be subject to abrasion. Data specifically 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 Au alloy and ceramic surfaces would be equivalent to that of contact-free occlusal surfaces. This ranges from 25% to 76% of the wear rate for occlusal surfaces with opposing teeth.34 Values for non-occulsal surface wear were assigned randomly for both dental materials, with any value between the minimum and maximum deemed equally likely.

Surface Area of Dental Restorations When considering crowns (five surface restorations on molars and premolars; four surface restorations on non-molar teeth), the entire surface of the subject tooth was assumed to be completely covered by the restoration. In this case, each occlusal and non-occlusal surface was assumed to be 90 mm2 in area.35 For restorations other than crowns, the Journal of Exposure Science and Environmental Epidemiology (2015), 1 – 8

Exposures from gold and ceramic dental materials Richardson et al

4 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

N (millions)4REL

N (millions)4REL

N (millions)4REL

c

Safe number of restored tooth surfaces (N)a

Safe number of restored teeth (N)b

Au alloy

Au Ag Cu Zn Pd Pt In

NA 98.71 1.06 0 67.76 74.61 7.41

NA 55.16 0.19 0 35.38 41.75 2.47

NA 5.91 0 0 1.54 2.90 0

NA 4 No limitd No limit 10 7 87

NA 2 No limite No limit 4 3 No limit

Ceramic

Si Al Mg Ti Sn Zn Ba Li B Hg0 BPA

0 0 0 0 0 0 0 54.41 0 148.4 0

0 0 0 0 0 0 0 27.85 0 143.7 0

0 0 0 0 0 0 0 0.88 0 100.8 0

No limit No limit No limit No limit No limit No limit No limit 15 No limit 1.7 No limit

No No No No No No No

Amalgamf Composite resinsg

limit limit limit limit limit limit limit 6 No limit 1 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 size was assumed to be 90 mm2. The surface area of restorations on specific tooth surfaces was assigned randomly, with any surface area between these values being equally likely.

The Proportion of Persons and Tooth Surfaces with Au or Ceramic 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 restorations, and also to discount tooth surfaces restored with any and all other dental materials. Unfortunately, the 2001–2004 NHANES surveys did not record the composition of the dental restorative materials present on filled tooth surfaces of survey participants, so information was necessarily compiled from other sources. Reports and literature concerning the relative use of different dental materials in the US and Canada have been reviewed in detail elsewhere,4 and will not be repeated here. To be consistent with the assessment of exposure and risks associated with dental amalgam, the assessment of exposure of adults to components of Au alloy and ceramic restorations was approached independently for each material, in three scenarios: ● ●



All dental restorations were assumed to be composed of Au alloy or 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 or ceramic. All other tooth surfaces were assumed to be restored with other materials. Only 30% of persons with dental restorations were assumed to have at least one Au or one ceramic restoration and, for this group, 11% of all restored tooth surfaces contained either Au alloy or ceramic. For this latter scenario, ~ 30% of dentists in the US are amalgam free,36 suggesting that their patients might have a pre-disposition to having all

Journal of Exposure Science and Environmental Epidemiology (2015), 1 – 8

Au or all ceramic restorations. In the only report quantifying the relative occurrence of Au alloys versus other restorative materials for a segment of the US adult population,37 10.7% of in-place restorations were 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 same assumption of 11% was also appropriate for ceramics.

Estimating Allowable Restorations of Au Alloy or Ceramic Material Based on Chemical Risk Whereas dose can be derived using Equation 1 above, a defined “safe” reference exposure level (REL; also known as reference dose, tolerable daily intake and so on) can be substituted for dose and the equation can be reversed to solve for the number (N) of filled tooth surfaces that will not result in exceeding the REL. The assumptions used to solve for N are summarized in footnotes to Table 5.

RELs for Components of Au Alloy and Ceramic Dental Materials Available RELs are presented in Table 1. Preference was given to those RELs published by the US Environmental Protection Agency (USEPA). Alternate sources were used when the USEPA had no current RELs available on its integrated risk information system, or from EPA Regions 3 or 9.

RESULTS The exposure estimates presented in Table 6 are the first published population-based estimates of exposures to components of Au alloy and ceramic dental restorations. Exposure statistics (mean, percentiles) were derived on the basis of the US adult population considered in each exposure scenario (indicated in Table 6), not on the total NHANES sample population. © 2015 Nature America, Inc.

Exposures from gold and ceramic dental materials Richardson et al

5 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 Population in scenariob Material

Component

Au alloy

Au Ag Cu Zn Pd Pt In

Ceramic

Si Al Mg Ti Sn Zn Ba Li B

1

2

3

151,299,412

76,675,777

45,331,121

Dose (μg/kg-day)

Dose (μg/kg-day)

Dose (μg/kg-day)

68.5 ± 102.8 (1.41–265.70; 1896.6) 22.1 ± 34.1 (0.45–87.87; 492.4) 11.8 ± 18.7 (0.23–46.85; 265.5) 1.3 ± 2.7 (0–5.97; 50.1) 4.1 ± 7.5 (0.06–16.65; 133.7) 7.3 ± 13.3 (0.1–31.29; 261.6) 1.9 ± 3.7 (0.01–8.14; 97.5) 23.2 ± 33.4 (0.52–91.19; 384.3) 5.8 ± 9.4 (0.11–22.06; 116.0) 0.9 ± 1.7 (0–3.84; 33.1) 0.5 ± 1.1 (0–2.34; 17.7) 0.9 ± 1.8 (0–3.85; 33.1) 1.4 ± 2.7 (0–5.99; 32.8) 0.4 ± 0.9 (0–1.63; 16.6) 3.0 ± 5.5 (0.002–12.35; 93.6) 1.2 ± 2.5 (0–5.25; 47.6)

61.4 ± 76.0 (3.60–227.52; 733.5) 19.5 ± 25.9 (1.03–65.81; 280.8) 10.7 ± 14.4 (0.58–38.22; 160.0) 1.1 ± 2.0 (0–4.54; 31.5) 3.7 ± 5.7 (0.14–13.97; 70.2) 6.6 ± 10.4 (0.18–26.57; 125.5) 1.7 ± 2.8 (0.03–6.55; 35.7) 21.6 ± 27.0 (1.06–71.41; 263.3) 5.4 ± 7.1 (0.24–19.10; 78.4) 0.8 ± 1.5 (0–3.42; 17.9) 0.5 ± 0.9 (0–2.07; 11.2) 0.8 ± 1.4 (0–3.28; 15.4) 1.3 ± 2.1 (0–5.25; 23.3) 0.3 ± 0.7 (0–1.47; 7.5) 2.7 ± 4.1 (0–10.53; 44.5) 1.2 ± 1.9 (0–4.44; 21.6)

7.3 ± 9.0 (0.30–26.33; 75.2) 2.3 ± 3.0 (0.09–8.77; 24.8) 1.3 ± 1.7 (0.04–4.71; 14.4) 0.1 ± 0.2 (0–0.59; 2.0) 0.4 ± 0.7 (0.01–1.69; 9.2) 0.8 ± 1.2 (0.02–3.12; 13.9) 0.2 ± 0.3 (0.002–0.80; 3.1) 2.4 ± 3.0 (0.09–9.12; 25.0) 0.6 ± 0.8 (0.02–2.32; 8.0) 0.1 ± 0.2 (0–0.35; 1.7) 0.1 ± 0.1 (0–0.33; 1.2) 0.1 ± 0.2 (0–0.39; 1.6) 0.1 ± 0.2 (0–0.61; 2.7) 0.04 ± 0.07 (0–0.17; 0.8) 0.3 ± 0.5 (0–1.26; 6.1) 0.1 ±0.2 (0–0.55; 1.9)

a Scenario 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 each restorative material that should not result in exceeding RELs for their component elements. Au Alloys The relatively high Ag content of dental Au alloys, combined with Ag’s relatively low REL (high-relative toxicity; Table 1), results in Ag being the most problematic component (Figure 1). Assuming that all dental restorations in the US population were composed of Au alloys (Scenario 1) would result in a significant number of US adults (98.7 million persons) receiving a dose that exceeds the reference dose for Ag. Such a situation would be extremely unlikely; however, the most realistic exposure scenario (Scenario 3) still suggests that the exposure received by some 5.9 million adults with Au alloy dental restorations would exceed the reference dose for Ag published by the USEPA. Exposure to metals released from Au alloys is such that the number of Au alloy restorations that can be present and not 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). Pt and Pd in Au alloy restorations also present some risk to the US population. Even with the most realistic scenario (Scenario 3), © 2015 Nature America, Inc.

2.9 million adults would exceed the REL for Pt and 1.5 million adults would exceed the REL for Pd (Table 5; Figure 1). These two elements have the highest relative toxicity (lowest RELs) of Au alloy components. Cu and In present no exceedences of their RELs for the third, most realistic, exposure scenario. Zn is the component of least concern with no exposures exceeding the REL for Zn in any of the three scenarios considered here. Au has the highest relative composition of all the components in Au alloys but no REL is available for inorganic Au from any national or international agency. Organo-Au compounds are known to be toxic,38 but no mammalian toxicological data are available for inorganic Au compounds. The release of Au from dental Au alloys leads to a relatively high incidence of allergic sensitivity, perhaps as high as 23% of those with Au restorations.39 Au from dental alloys is excreted in urine,40–42 and reaches the blood,16 in concentrations proportional to dental Au load. Further research is required to establish an oral REL for inorganic Au, to permit a quantitative assessment of potential risks posed by exposure to this component of Au dental alloys. Ceramics Li is more toxic than the other ceramic components (Table 1). This, combined with the Li content of some ceramic materials (range up Journal of Exposure Science and Environmental Epidemiology (2015), 1 – 8

Exposures from gold and ceramic dental materials Richardson et al

6

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 some extent in all scenarios (Table 5; Figure 1). For the most realistic Scenario 3, the REL could be exceeded in some 880,000 US adults with ceramic dental restorations. Exposures to components other than Li are much less compared with their respective RELs, even when it is assumed that all dental restorations in the adult population are composed of ceramics (see Scenario 1, Table 6 and Table 5). If the Li content of ceramics is ≤ 0.5% by weight, estimates of maximum Li exposure are greatly reduced, and no limits on the number of ceramic restorations would be evident. The estimated exposures to Li from ceramic restorations are conservative as they represent total ingestion exposures, and not systemically absorbed doses. Soluble Li compounds are readily absorbed from the gastrointestinal tract.43,44 There is evidence 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 o100% of available Li. Future investigation of the gastrointestinal solubility of Li from ceramics is warranted. Leaching of Metals from Au Alloy and Ceramic Dental Restorations Leaching of ions from Au alloy and ceramic restorations was omitted from our analysis. Metal ions have been observed in the saliva of dental patients with these restorations;15,41,42,46 however, levels in saliva will be a combination of loss owing to both leaching and wear. A preliminary analysis (computations not shown) suggests that the contribution of leaching to exposure may be low (o 15%), relative to dental material wear. However, an assessment should be undertaken to quantify exposure specifically because of leaching, to complement the analysis on material wear presented herein. Journal of Exposure Science and Environmental Epidemiology (2015), 1 – 8

Comparisons with Amalgam and Composite Resin The estimates of exposure and risk presented herein have been derived in a manner that permits direct comparison with estimated mercury vapor (Hg0) exposures from dental amalgam,4 as well as components and degradation products of composite resin dental restorations.7,8 Figure 2 presents information comparable to Figure 1, but for exposure to Hg0 from dental amalgam, and exposure to BPA from composite resins. Table 5 also includes numbers of filled tooth surfaces for dental amalgam and composite resins that should not result in exceeding RELs for their component elements or substances, for direct comparison to Au alloys and ceramics. Based on review of Figures 1 and 2, and Table 5, relative risks of chemical exposures from dental materials compare as follows: Dental amalgam4Au alloy4ceramics4composite resins. DISCUSSION There are no regulatory requirements for premarket exposure and risk assessment of dental restorative materials in the US, Canada or elsewhere. As a result, regulatory agencies facing challenges to dental material safety undertake ad hoc and inconsistent approaches to resolve criticisms, typically with no supporting quantitative exposure and risk analysis.2,47,48 Quantitative exposure and risk assessment should be a component of that evaluation process, but cannot be the only consideration. Research is published routinely on the efficacy of dental materials (leaching, clinical performance, longevity, recurrent decay and so on). However, a standard, routine, systematic and quantitative approach to the evaluation of the relative efficacy, benefits, exposures and risks is needed for all dental materials, particularly given the 130 million dental restorations that are placed annually © 2015 Nature America, Inc.

Exposures from gold and ceramic dental materials Richardson et al

7

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.

in the US population.1 This information should be critically evaluated, and publically available, to help dental clinicians, in consultation with their patients, determine which restorative materials are optimum for use. CONFLICT OF INTEREST The authors declare no conflict of interest.

ACKNOWLEDGMENTS Funding for this project was provided by the Natural Sciences and Engineering Research Council of Canada, Collaborative Research and Training Experience (CREATE) Grant in Human and Ecological Risk Assessment (HERA), to SDS and GMR. Funding in kind, for time committed by GMR and SRC, was provided, respectively, by Stantec Consulting, and SNC-Lavalin Environment, both of Ottawa, Ontario, Canada.

REFERENCES 1 Beazoglou T, Eklund S, Heffley D, Meiers J, Brown LJ, Bailit H. Economic impact of regulating the use of amalgam restorations. Public Health Rep 2007; 122: 657–663. 2 USFDA (US Food and Drug Administration). White Paper: FDA Update/Review of Potential Adverse Health Risks Associated with Exposure to Mercury in Dental Amalgam. National Center for Toxicological Research, USFDA: Washington, DC, 2009. 3 Richardson GM. Mercury exposure and risks from dental amalgam in Canada: the Canadian Health Measures Survey 2007–2009. Hum Ecol Risk Assess 2014; 20: 433–447. 4 Richardson GM, Wilson R, Allard D, Purtill C, Douma S, Gravière J. Mercury exposure and risks from dental amalgam in the US population, post-2000. Sci Total Environ 2011; 409: 4257–4268. 5 Richardson GM. Inhalation of mercury-contaminated particulate matter by dentists: an overlooked occupational risk. Hum Ecol Risk Assess 2003; 9: 1519–1531. 6 Richardson GM, Evidence that bisphenol-a exposure is not associated with composite resin dental fillings. E-Letter, PediatricsOnline at http://pediatrics.aap publications.org/content/130/2/e328/reply. Published August 21 2012. 7 Richardson GM. Assessment of adult exposure and risks from components and degradation products of composite resin dental materials. Hum Ecol Risk Assess 1997; 3: 683–697. 8 Richardson GM, Clark KE, Williams DR. Preliminary estimates of adult exposure to bisphenol-a from dental materials, food and ambient air. In: Henshel DS, Black MC, Harrass MC (eds). Environmental Toxicology and Risk Assessment: Standardization of Biomarkers for Endocrine Disruption and Environmental Assessment: Eighth Volume, American Society for Testing and Materials: West Conshohocken, PA, 1999 pp 286–301. 9 Joskow R, Barr DB, Barr JR, Calafat AM, Needham LL, Rubin C. Exposure to bisphenol A from bis-glycidyl dimethacrylate-based dental sealants. J Am Dent Assoc 2006; 137: 353–362.

© 2015 Nature America, Inc.

10 Zimmerman-Downs JM, Shuman D, Stull SC, Ratzlaff RE. Bisphenol A blood and saliva levels prior to and after dental sealant placement in adults. J Dent Hyg 2010; 184: 145–150. 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/ Fall 2010. 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. 13 Tran LA, Messer LB. Clinicians’ choices of restorative materials for children. Austral Dent J 2003; 48: 221–232. 14 Peretz B, Ram D. Restorative material for children's teeth: preferences of parents and children. ASDC J Dent Child 2002; 69: 233. 15 Elshahawy W, Ajlouni R, James W, Abdellatif H, Watanabe I. Elemental ion release from fixed restorative materials into patient saliva. J Oral Rehabil 2013; 40: 381–385. 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 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 1980; 13: 117–124. 19 Donaldson JA. The use of gold in dentistry: an historical overview, part 2. Gold Bull 1980; 13: 160–165. 20 Christensen G J. Longevity versus esthetics: the great restorative debate. J Am Dent Assoc 2007; 138: 1013–1015. 21 Knosp H, Holliday RJ, Corti CW. Gold in dentistry: alloys, uses and performance. Gold Bull 2003; 36: 93–101. 22 ADA (American Dental Association). Grills, ‘grillz’ and fronts. J Am Dent Assoc 2006; 137: 1192. 23 Leinfelder KF. An evaluation of casting alloys used for restorative procedures. J Am Dent Assoc 1997; 128: 37–45. 24 Chu S, Ahmad I. A historical perspective of synthetic ceramic and traditional feldspathic porcelain. Pract Proced Aesthet Dent 2005; 17: 593–598. 25 Jones DW. A brief overview of dental ceramics. J Can Dent Assoc 1998; 64: 648–650. 26 Kukiattrakoon B, Hengtrakool C, Kedjarune-Leggat U. The effect of acidic agents on surface ion leaching and surface characteristics of dental porcelains. J Prosthet Dent 2010; 103: 148–162. 27 Christensen GJ. The coming demise of the cast gold restoration? J Am Dent Assoc 1996; 127: 1233–1236. 28 Mormann WH. The evolution of the CEREC system. J Am Dent Assoc 2006; 137: 7S–13S. 29 Eley BM. The future of dental amalgam: a review of the literature. Part 7: possible alternative materials to amalgam for the restoration of posterior teeth. Br Dent J 1997; 183: 11–14. 30 USEPA (US Environmental Protection Agency). Risk Assessment Guidance for Superfund: Volume III - Part A, Process for Conducting Probabilistic Risk Assessment Report EPA 540-R-02-002. Office of Emergency and Remedial Response, USEPA: Washington, DC, 2001.

Journal of Exposure Science and Environmental Epidemiology (2015), 1 – 8

Exposures from gold and ceramic dental materials Richardson et al

8 31 NCHS (National Center for Health Statistics). Analytic and Reporting Guidelines: The National Health and Nutrition Examination Survey (NHANES). Centers for Disease Control and Prevention: Hyattsville, Maryland, 2005. 32 Al-Hiyasat AS, Saunders WP, Sharkey SW, Smith GM, Gilmour WH. Investigation of human enamel wear against four dental ceramics and gold. J Dent 1998; 26: 487–495. 33 Yip KH-K, Smales RJ, Kaidonis JA. Differential wear of teeth and restorative materials: clinical implications. Int J Prosthodon 2004; 17: 350–356. 34 Willems G, Lambrechts P, Braem M, Vanherle G, Classification and wear of dental composites. Proc. Int. Symp. on State-of-the-art on Direct Posterior Filling Materials and Dentin Bonding, Paris 1993. 35 Kraus B S, Jordan R E, Abrams L Dental Anatomy and Occlusion. Williams and Wilkins, Co: Baltimore, MD, 1978. 36 Haj-Ali R, Walker M P, Williams K. Survey of general dentists regarding posterior restorations, selection criteria, and associated clinical problems. Gen Dent 2005; 53: 369–375. 37 Albertini T F, Kingman A, Brown J. Prevalence and distribution of dental restorative materials in US air force veterans. J Public Health Dent 1997; 57: 5–10. 38 Kean WF, Kean IRL. Clinical pharmacology of gold. Inflammopharmacology 2008; 16: 112–125. 39 Eisler R. Mammalian sensitivity to elemental gold (Au0). Biol Trace Elem Res 2004; 100: 1–17. 40 Benemann J, Lehmann N, Bromen K, Marr A, Seiwert M, Schulz C, Jockel K-H. Assessing contamination paths of the German adult population with gold and platinum. The German Environmental Survey 1998 (GerES III). Int J Hyg Environ Health 2005; 208: 499–508. 41 Schierl R. Urinary platinum levels associated with dental gold alloys. Arch Environ Health 2001; 56: 283–286. 42 Drasch G,; Muss C, Roider G. Gold and palladium burden from dental restoration materials. J Trace Elem Med Biol 2000; 14: 71–75. 43 Schrauzer GN. Lithium: occurrence, dietary intakes, nutritional essentiality. J Am Coll Nutr 2002; 21: 14–21. 44 Shiotsuki I, Terao T, Ogami H, Ishii N, Yoshimura R, Nakamura J. Drinking spring water and lithium absorption: a preliminary study. Ger J Psychiatry 2008; 11: 103–106. 45 Milleding P, Haraldsson C, Karlsson S. Ion leaching from dental ceramics during static in vitro corrosion testing. J Biomed Mater Res 2002; 61: 541–550. 46 Garhammer P, Hiller KA, Reitinger T, Schmalz G. Metal content of saliva of patients with and without metal restorations. Clin Oral Investig 2004; 8: 238–242. 47 CADTH (Canadian Agency for Drugs and Technologies in Health). Composite Resin and Amalgam Dental Filling Materials: A Review of Safety, Clinical Effectiveness and Cost-effectiveness. CADTH: Ottawa, Canada, 2012. 48 SCENIHR (Scientific Committee on Emerging and Newly-Identified Health Risks). Scientific opinion on the Safety of Dental Amalgam and Alternative Dental Restoration Materials for Patients and Users. Health and Consumer Protection Directorate-General, European Commission: Brussels, 2008. 49 Begerow J, Neuendorf J, Turfeld M, Raab W, Dunemann L. Long-term urinary platinum, palladium, and gold excretion of patients after insertion of noble-metal dental alloys. Biomarkers 1999; 4: 27–36. 50 Lopez-Alias J F, Martinez-Gomis J, Anglada J M, Peraire M. Ion release from dental casting alloys as assessed by a continuous flow system: nutritional and toxicological implications. Dent Mater 2006; 22: 832–837. 51 Sjogren G, Sletten G, Dahl JE. Cytotoxicity of dental alloys, metals, and ceramics assessed by millipore filter, agar overlay, and MTT tests. J Prosthet Dent 2000; 84: 229–236. 52 Wataha JC, Lockwood PE. Release of elements from dental casting alloys into cellculture medium over 10 months. Dent Mater 1998; 14: 158–163. 53 Elshahawy W, Watanabe I, Koike M. Elemental ion release from four different fixed prosthodontic materials. Dent Mater 2009; 25: 976–981. 54 Hero H, Jorgensen R, Sorbroden E. A low-gold dental alloy–structure and segregations. J Dent Res 1982; 61: 1292–1298. 55 Johansson G, Bergman M, Anneroth G, Eskafi M. Human pulpal response to direct filling gold restorations. Scand J Dent Res 1993; 101: 78–83. 56 Lappalainen R, Yli-Urpo A. Release of elements from some gold-alloys and amalgams in corrosion. Scand J Dent Res 1987; 95: 364–368. 57 Ogino T, Koizumi H, Furuchi M, Murakami M, Matsumura H, Tanoue N. Effect of a metal priming agent on wear resistance of gold alloy-indirect composite joint. Dent Mater J 2007; 26: 201–208. 58 Ucar Y, Brantley WA, Johnston WM, Dasgupta T. Mechanical properties, fracture surface characterization, and microstructural analysis of six noble dental casting alloys. J Prosthet Dent 2011; 105: 394–402. 59 Wataha JC. Alloys for prosthodontic restorations. J Prosthet Dent 2002; 87: 351–363. 60 Wataha JC, Lockwood PE, Khajotia SS, Turner R. Effect of pH on element release from dental casting alloys. J Prosthet Dent 1998; 80: 691–698.

Journal of Exposure Science and Environmental Epidemiology (2015), 1 – 8

61 USEPA (US Environmental Protection Agency). Integrated Risk Information System (IRIS). Online at http://www.epa.gov/iris/. Accessed on 15 December 2013. 62 Health Canada. Federal Contaminated Site Risk Assessment in Canada Part II: Health Canada Toxicological Reference Values (TRVs) and Chemical-Specific Factors, Version 20. Contaminated Sites Division, Health Canada: Ottawa, ON, Canada, 2010. 63 EMA (European Medicines Agency). Guideline on the specification limits for residues of metal catalysts, Doc. Ref. CPMP/SWP/QWP/4446/00 corr Committee for Human Medicinal Products, EMA: London, UK, 2007. 64 Moskowitz PD, Bernholc N, DePhillips MP, Viren J Derived reference doses for three compounds used in the photovoltaics industry: copper indium diselenide, copper gallium diselenide, and cadium telleride Report BNL-62045. Biomedical and Environmental Assessment Group, Analytical Sciences Division, Department of Applied Science, Brookhaven National Laboratory: Long Island, NY, Dated July 6 1995. 65 Anusavice KJ. Degradability of dental ceramics. Adv Dent Res 1992; 6: 82–89. 66 Elmaria A, Goldstein G, Vijayaraghavan T, Legeros RZ, Hittelman EL. An evaluation of wear when enamel is opposed by various ceramic materials and gold. J Prosthet Dent 2006; 96: 345–353. 67 Jakovac M, Zivko-Babic J, Curkovic L, Aurer A. Measurement of ion elution from dental ceramics. J Europ Ceram Soc 2006; 26: 1695–1700. 68 Kase HR, Tesk JA, Case ED. Elastic constants of two dental porcelains. J Mater Sci 1985; 20: 524–531. 69 Roy S, Basu B. Hardness properties and microscopic investigation of crack–crystal interaction in SiO2–MgO–Al2O3–K2O–B2O3–F glass ceramic system. J Mater Sci Mater Med 2010; 21: 109–122. 70 Santos C, Souza RC, Almeida N, Almeida FA, Silva RRF, Fernandes MHFV. Toughened ZrO2 ceramics sintered with a La2O3-rich glass as additive. J Mater Process Technol 2008; 200: 126–132. 71 Uo M, Sjoren G, Sundh A, Watari F, Bergman M, Lerner U. Cytotoxicity and bonding property of dental ceramics. Dent Mater 2003; 19: 487–492. 72 Zhang Y, Kim J-W. Graded structures for damage resistant and aesthetic all-ceramic restorations. Dent Mater 2009; 25: 781–790. 73 UKEGVM (UK Expert Group on Vitamins and Minerals). Safe Upper Levels for Vitamins and Minerals. UKEGVM, Committee on Toxicology, Food Standards Agency: UK, 2003. 74 USEPA (US Environmental Protection Agency). Regional Screening Level (RSL) Summary Table. USEPA, Region 3. Online at http://www.epa.gov/reg3hwmd/risk/ human/rb-concentration_table/Generic_Tables/ index.htm. Accessed 15 December 2013. 75 NVDEP (Nevada Division of Environmental Protection). Technical memorandum: Toxicity Criteria for Titanium and Compounds, and for Tungsten and Compounds. Nevada State Department of Conservation and Natural Resources, 2008. 76 Hacker CH, Wagner WC, Razzoog ME. An in vitro investigation of the wear of enamel on porcelain and gold in saliva. J Prosthet Dent 1996; 75: 14–17. 77 Ramp MH, Suzuki S, Cox CF, Lacefield WR, Koth DL. Evaluation of wear: enamel opposing three ceramic materials and a gold alloy. J Prosthet Dent 1997; 77: 523–530. 78 Graf K, Johnson GH, Mehl A, Rammelsberg P. The influence of dental alloys on three-body wear of human enamel and dentin in an inlay-like situation. Oper Dent 2002; 27: 167–174. 79 Suzuki S, Nagai E, Taira Y, Minesaki Y. In vitro wear of indirect composite restoratives. J Prosthet Dent 2002; 88: 431–436. 80 Ohkubo C, Shimura I, Aoki T, Hanatani S, Hosoi T, Hattori M, Oda Y, Okabe T. Wear resistance of experimental Ti-Cu alloys. Biomaterials 2003; 24: 3377–3381. 81 Alarcon JV, Engelmeier RL, Powers JM, Triolo. PT. Wear testing of composite, gold, porcelain, and enamel opposing a removable cobalt–chromium partial denture alloy. J Prosthodont 2009; 18: 421–426. 82 Delong R, Douglas WH, Sakaguchi RL, Pintado MR. The wear of dental porcelain in an artificial mouth. Dent Mater 1986; 2: 214–219. 83 Leinfelder KF, Suzuki S. In vitro wear device for determining posterior composite wear. J Am Dent Assoc 1999; 130: 1347–1353. 84 Al-Hiyasat AS, Saunders WP, Smith GM. Three-body wear associated with three ceramics and enamel. J Prosthet Dent 1999; 82: 476–481. 85 Krejci I, Lutz F, Reimer M, Heinzmann JL. Wear of ceramic inlays, their enamel antagonists, and luting cements. J Prosthet Dent 1993; 69: 425–430. 86 Ramp MH, Ramp LC, Suzuki S. Vertical height loss: an investigation of four restorative materials opposing enamel. J Prosthodont 1999; 8: 252–257. 87 Richardson GM, Brecher R, Scobie H, Hamblen J, Phillips K, Samuelian J, Smith C. Mercury vapour (Hg0): continuing toxicological uncertainties, and establishing a Canadian reference exposure level. Regul Toxicol Pharmacol 2009; 53: 32–38. 88 Willhite CC, Ball GL, McLellan CJ. Derivation of a bisphenol A oral reference dose (RfD) and drinking-water equivalent concentration.J Toxicol Environ Health B Crit Rev 2008; 11: 69–146. 89 USEPA (US Environmental Protection Agency). Integrated Risk Information System (IRIS). Online at http://www.epa.gov/iris/. Accessed 7 January 2015.

© 2015 Nature America, Inc.

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

Little has been published on the chemical exposures and risks of dental restorative materials other than from dental amalgam and composite resins. Her...
665KB Sizes 0 Downloads 7 Views