38686 Federal Register / Vol. 74, No. 148 / Tuesday, August 4, 2009 / Rules and Regulations 

1 General controls are specifically identified in 

the statute and include requirements such as 

adverse event reporting and good manufacturing 

practices. General controls are applicable to any 

class of device. Special controls are controls 

identified and designated by the Agency as controls 

in addition to the general controls that apply to a 

specific device to address the specific risks to 

health of that device. 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Part 872 

[Docket No. FDA–2008–N–0163; Formerly 

Docket No. 2001N–0067] 

RIN 0910–AG21 

Dental Devices: Classification of 

Dental Amalgam, Reclassification of 

Dental Mercury, Designation of Special 

Controls for Dental Amalgam, Mercury, 

and Amalgam Alloy 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final rule. 

SUMMARY: The Food and Drug 

Administration (FDA) is issuing a final 

rule classifying dental amalgam into 

class II, reclassifying dental mercury 

from class I to class II, and designating 

a special control to support the class II 

classifications of these two devices, as 

well as the current class II classification 

of amalgam alloy. The three devices are 

now classified in a single regulation. 

The special control for the devices is a 

guidance document entitled, ‘‘Class II 

Special Controls Guidance Document: 

Dental Amalgam, Mercury, and 

Amalgam Alloy.’’ This action is being 

taken to establish sufficient regulatory 

controls to provide reasonable assurance 

of the safety and effectiveness of these 

devices. Elsewhere in this issue of the 

Federal Register, FDA is announcing 

the availability of the guidance 

document that will serve as the special 

control for the devices. 

DATES: This rule is effective November 

2, 2009. 

FOR FURTHER INFORMATION CONTACT: 

Michael E. Adjodha, Food and Drug 

Administration, Center for Devices and 

Radiological Health, 10903 New 

Hampshire Ave., Bldg. 66, rm. 2606, 

Silver Spring, MD 20993–0002, 301– 

796–6276. 

SUPPLEMENTARY INFORMATION: 

I. Background 

A. Overview 

1. Review of Scientific Evidence 

a. Evidence Related to the Population Age 

Six and Older 

i. Air Monitoring Standards for Elemental 

Mercury Vapor 

ii. Biological Monitoring Standards for 

Urine Mercury 

iii. Clinical Studies 

b. Evidence Related to Special Populations 

i. Potentially Sensitive Subpopulations 

(Developing Fetuses, Breastfed Infants, 

and Children Under Age Six) 

ii. Dental Professionals 

iii. Individuals with Mercury Allergies 

2. Rationale for Special Controls 

a. Risk of Exposure to Mercury 

i. Specific Labeling Recommendations 

ii. Information for Use Recommendation 

iii. Performance Test Recommendation 

b. Risk of Allergic Response Including 

Adverse Tissue Reaction 

i. Specific Labeling Recommendations 

ii. Performance Test Recommendation 

c. Risk of Mercury Contamination 

d. Risk of Mechanical Failure 

i. Specific Labeling Recommendation 

ii. Performance Test Recommendation 

e. Risk of Corrosion 

i. Specific Labeling Recommendation 

ii. Performance Test Recommendation 

f. Risk of Improper Use 

B. Statutory Authority 

C. Regulatory History of the Devices 

1. Regulatory Status 

2. Proposed Rule 

3. Scientific Information, Safety 

Assessments, and Adverse Event Reports 

Regarding Dental Amalgam 

a. Information and Assessments Discussed 

in the Proposed Rule 

b. Information and Assessments That Have 

Become Available Since Publication of 

the Proposed Rule 

i. Life Sciences Research Office (LSRO) 

Report 

ii. White Paper and Addendum Scientific 

Reviews 

c. Adverse Event Reports 

II. Development of the Final Rule 

III. Comments and FDA’s Responses 

A. Classification 

B. Banning 

C. Mercury Content and Toxicity 

D. Patient Information 

E. Alternative Materials 

F. Need for Public Hearings 

G. Accusations of FDA Bias 

H. Preemption 

I. Environmental Concerns 

IV. Environmental Impact 

V. Analysis of Impacts 

A. Introduction 

B. Summary of Economic Impacts 

C. Objective and Need of the Final Rule 

D. Risk 

E. Baseline in the Absence of the Final 

Rule 

F. The Final Rule 

G. Costs of the Final Rule 

1. Manufacturing Costs 

a. Testing Costs 

b. Labeling Costs Associated With the Final 

Rule 

c. Increased Manufacturing Costs 

2. Costs of FDA Regulatory Oversight 

3. Total Costs 

H. Potential Public Health Effects of the 

Final Rule 

I. Alternatives to the Final Rule 

1. No New Regulatory Action 

2. Class II But With Other Special Controls 

3. Reclassification to Class III 

4. Ban the Use of Mercury in Dental 

Restorations 

J. Regulatory Flexibility Analysis 

VI. Federalism 

VII. The Paperwork Reduction Act of 1995 

VIII. References 

I. Background 

The following section provides an 

overview of the final rule, applicable 

statutory authority for classifying 

devices, the regulatory history of these 

dental devices, scientific information 

and safety assessments involving the 

devices, and the development of this 

rule. 

A. Overview 

Dental amalgam is a metallic 

restorative material that is used for 

direct filling of carious lesions or 

structural defects in teeth. It is a 

combination of mercury (liquid) and 

amalgam alloy (powder), which is 

composed primarily of silver, tin, and 

copper. 

As discussed in detail in this 

preamble, this final rule classifying 

dental amalgam reflects FDA’s careful 

consideration of the valid scientific 

evidence related to dental amalgam’s 

benefits, which include its effectiveness 

as a restorative material, strength, and 

durability, and its potential risks, which 

include those related to the release of 

low levels of mercury vapor. FDA is 

required by statute to classify devices 

(21 U.S.C. 360c). This final rule 

classifies the device ‘‘dental amalgam’’ 

into class II and reclassifies the device 

‘‘dental mercury’’ (hereinafter 

‘‘mercury’’) from class I to class II. 

Importantly, the rule also establishes 

special controls for dental amalgam, 

mercury, and amalgam alloy (mercury 

and amalgam alloy are combined to 

form dental amalgam). Special controls 

are established to provide a reasonable 

assurance of safety and effectiveness for 

class II devices and are in addition to 

the general controls already applicable 

to any device.1 This rule designates a 

special controls guidance document 

with performance data and labeling 

recommendations as the special controls 

for dental amalgam. 

The Agency has determined that class 

II with special controls is the 

appropriate classification for dental 

amalgam after evaluating the valid 

scientific evidence related to dental 

amalgam, including comprehensive 

reviews of the scientific literature and 

safety assessments. Based on its review 

of this scientific evidence, FDA made 

the two findings it is required by law to 

make when classifying a device (21 CFR 

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Federal Register / Vol. 74, No. 148 / Tuesday, August 4, 2009 / Rules and Regulations 38687 

2Earlier prototypes were available beginning in 

the 1830s. 

3Over 50 million dental amalgam restorations are 

placed per year in the United States (Ref. 2). 

860.7(d)(1)): First, FDA found that, 

when subject to the general controls of 

the act and the designated special 

control, the probable benefits to health 

from the use of the device for its 

intended use and conditions for use, 

when accompanied by adequate 

directions and warnings against unsafe 

use, outweigh any probable risks. 

Second, FDA found that, when subject 

to the general controls of the act and the 

designated special control, the scientific 

evidence adequately demonstrates the 

absence of unreasonable risk of illness 

or injury associated with the intended 

use of dental amalgam. 

In developing this final rule, FDA 

reviewed scientific evidence and also 

considered the classification 

recommendation of the Dental Products 

Panel (Ref. 1), which concluded that 

there are no major risks associated with 

encapsulated dental amalgam, when 

used as directed, but recognized there is 

a small population of patients who may 

experience allergic hypersensitive 

reactions to the materials in the device. 

The Panel also noted that improper use 

exposes dental professionals to risks 

associated with mercury toxicity, with 

improper storage, trituration, and 

handling contributing to this risk. 

As part of its assessment, FDA 

considered the important public health 

benefits of dental amalgam and the 

advantages it presents as a restorative 

material. 

Dental amalgam has been used since 

the 1890s.2 Millions of patients have 

received dental amalgam restorations to 

treat dental caries.3

A dentist’s decision concerning the 

use of a particular restorative material is 

complex, involving factors related to the 

tooth, the patient, the clinician and the 

properties of the restorative materials. 

The dentist must, among other 

considerations, take into account the 

patient’s age, caries history, oral 

hygiene, ability to maintain a dry field, 

degree of tooth destruction and the 

necessity to perform a procedure 

quickly and efficiently due to a patient’s 

ability to cooperate. Specific clinical 

situations may limit the restoration 

options. Dental amalgam provides 

advantages in that it may be placed 

quickly in a wet field while providing 

high strength, durability, longevity, and 

marginal integrity, features that may 

help prevent recurrent decay. Dental 

amalgams are typically used: 

• In stress-bearing areas and in small 

to moderate sized cavities in posterior 

teeth; 

• In teeth with severe destruction; 

• As a foundation for cast-metal, 

metal-ceramic and ceramic restorations; 

• When a patient’s commitment to 

oral hygiene is poor; and/or 

• When moisture control is 

problematic. 

Dental amalgam may provide benefits 

over other dental restorative materials 

because amalgam fillings offer a broad 

range of applicability in clinical 

situations, ease of use and relative 

insensitivity to variations in handling 

technique and oral conditions (Refs. 

3–7). 

FDA also considered the potential 

risks of dental amalgam. Dental 

amalgam is a combination of elemental 

mercury (liquid) and amalgam alloy 

(powder), which is composed primarily 

of silver, tin, and copper. FDA’s 

assessment focused on the risks 

associated with the presence of mercury 

in the device. 

Mercury is a toxic metal that exists 

naturally in several forms in the 

environment: Elemental metallic 

mercury, inorganic mercury (ionic salt 

forms), and methylmercury (Ref 70, Ref. 

69). Elemental metallic mercury is 

highly volatile and releases mercury 

vapor. This form of mercury has a wellstudied toxicity profile and its toxicity 

is dependent on dose and exposure 

conditions. The toxicokinetics and 

adverse effects associated with mercury 

vapor are different from those associated 

with methylmercury. These differences 

include route of exposure (mercury 

vapor is inhaled while methylmercury 

is ingested), percent of dose that is 

absorbed (80% in the case of mercury 

vapor; 95% in the case of 

methylmercury), and toxicity profiles 

(Ref. 69, Ref. 70). 

Dental amalgam releases low levels of 

mercury vapor, with higher amounts 

released with mastication and gum 

chewing (Ref. 3). Higher levels of 

exposure to elemental mercury vapor 

are also associated with placement and 

removal of dental amalgams. For 

example, urinary mercury 

concentrations in 43 children ages 5 to 

7 years before and after amalgam 

placement (1–4 teeth filled) were 3.04 ± 

1.42 μg Hg/L (2.34 μg Hg/g Cr) and 4.20 

± 1.60 μg Hg/L (3.23 μg Hg/g Cr), 

respectively (Ref. 8). Removal of 

amalgams resulted in an increase in 

urinary mercury; values were 1.8 ± 1.2 

μg Hg/L (1.4 μg Hg/g Cr) before removal 

compared to 2.8 ± 2.1 μg Hg/L (2.2 μg/ 

g Cr) at 10 days post-removal (Ref. 9). 

After inhalation, approximately 70– 

80% of a mercury vapor dose is 

absorbed by the lung, enters the 

systemic circulation, distributes to 

several organ systems in varying 

amounts, and excretion occurs generally 

via the urinary route (Ref. 70). Because 

of its high lipid solubility, mercury 

vapor readily diffuses into erythrocytes 

and is oxidized by the catalasehydrogen peroxide complex to divalent 

mercuric ion (Hg2∂) (Ref. 70). Despite 

this rapid oxidation and intracellular 

localization, a fraction of the elemental 

mercury dose crosses the blood-brain 

barrier. Once inside cells, mercury 

vapor is also oxidized to mercuric ions 

(Hg2+) that are unable to diffuse back 

across the cell membrane (Ref. 70). The 

mercuric ion is believed to be the 

proximate toxic species responsible for 

the adverse health effects of inhaled 

mercury vapor. The mercuric ion has a 

biological half-life of two months (Ref. 

69, Ref. 70). 

While mercury toxicity has been 

demonstrated in a variety of organ 

systems in laboratory studies, the 

central nervous system (CNS) and the 

kidneys are both target organs sensitive 

to mercury vapor (Ref. 69). 

The first signs of mercury vapor 

toxicity at high doses are subtle effects 

on the nervous system, such as changes 

in nerve conduction, slight tremor, 

abnormalities in 

electroencephalography (EEG) patterns, 

and changes in motor functions, 

cognitive functions, and behavior. (Ref. 

69, Ref. 70). With progressively higher 

exposures, these effects become more 

pronounced and include prominent 

tremor, ataxia (incoordination), memory 

loss, psychological distress, irritability, 

excitability, depression, and gingivitis 

(inflammation of the gums) (Refs. 69, 

70). 

Mercury also accumulates in the 

kidneys. Adverse renal effects can range 

from reversible proteinuria (protein in 

the urine) to irreversible nephrotic 

syndrome, depending on the degree of 

exposure to mercury vapor (Ref. 69, Ref. 

70). 

In addition to crossing the blood-brain 

barrier, mercury vapor has been shown 

in animal studies to cross the placenta 

and reach the fetal brain (Ref. 48, Ref. 

44) is also able to cross the placenta and 

reach the fetal brain. Inorganic mercury, 

most likely in the form of Hg2∂, is 

found in breast milk after maternal 

exposure to mercury vapor and, 

therefore, may be present in breastfed 

infants (Ref. 55). Because maternal 

exposure to mercury vapor from dental 

amalgam may lead to prenatal and 

postnatal exposure of offspring, FDA 

considered the potential health effects 

of dental amalgam on developing 

fetuses and breastfed infants. 

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38688 Federal Register / Vol. 74, No. 148 / Tuesday, August 4, 2009 / Rules and Regulations 

4FDA decided to conduct this comprehensive 

review of the literature and prepare the Addendum 

rather than revise the White Paper. 

5These groups included the U.S. Public Health 

Service and the Environmental Health Policy 

Committee’s Working Group on Dental Amalgam 

(Refs. 3, 12). 

6The LSRO report examined studies published 

from 1996 through 2003. In conducting its review, 

LSRO engaged an independent panel of academic 

experts in the fields of immunotoxicology, 

immunology, and allergy; neurobehavioral 

toxicology and neurodevelopment; pediatrics; 

developmental and reproductive toxicology; 

toxicokinetics and modeling; occupational health 

and epidemiology; pathology; and general 

toxicology. (Ref. 13) 

7ATSDR defines a Minimal Risk Level (MRL) as 

follows: ‘‘An MRL is an estimate of the daily human 

exposure to a hazardous substance that is likely to 

be without appreciable risk of adverse noncancer 

health effects over a specified duration of exposure. 

* * * [MRLs] are set below levels that, based on 

current information, might cause adverse health 

effects in the people most sensitive to such 

substance induced effects’’ (http:// 

www.atsdr.cdc.gov/mrls/). 

8EPA defines a Reference Concentration (RfC) as 

follows: ‘‘An estimate (with uncertainty spanning 

perhaps an order of magnitude) of a continuous 

inhalation exposure to the human population 

(including sensitive subgroups) that is likely to be 

without an appreciable risk of deleterious effects 

during a lifetime. It can be derived from a NOAEL 

[No Observed Adverse Event Level], LOAEL 

[Lowest Observed Adverse Event Level], or 

benchmark concentration, with uncertainty factors 

generally applied to reflect limitations of the data 

used’’ (http://www.epa.gov/ncea/iris/ 

help_gloss.htm#r). 

9After considering a large body of literature, 

ATSDR derived the MRL for elemental mercury 

from a study of 26 workers exposed to low levels 

of mercury (0.026 mg/m3) in three industrial 

settings for an average of 15.3 years (range 1–41 

years) (Ref. 16). Urinary mercury concentrations for 

this study averaged 11.3 μmol/mol creatinine (Cr) 

(approximately 20.1 μg/g Cr; 26.1 μg/L urine). 

Continuous exposure was taken into account by 

converting workplace exposures of 8 hr/day-5 days/ 

week into exposures of 24 hr/day-7 days/week. 

Uncertainty factors (UFs) were used in deriving the 

MRL included variability in sensitivity to mercury 

within the human population (UF = 10) and the use 

of a lowest observed adverse effect level (LOAEL)— 

in this study, increased average velocity of naturally 

occurring hand tremors—instead of a no observed 

adverse effect level (NOAEL). In deriving the MRL, 

the ATSDR applied a less conservative uncertainty 

factor for the LOAEL (UF = 3), an approach 

commonly used when the endpoint is determined 

to be a less serious effect. In total, an uncertainty 

factor of 30 was applied. Application of the 

exposure conversions and uncertainty factors 

yielded a tolerable mercury vapor intake 

concentration of 0.2 μg/m3 for chronic inhalation 

exposure. The derivation of the ATSDR MRL for 

chronic exposure to mercury vapor also considered 

supporting evidence from several more recent 

studies that showed effect levels and adverse 

outcomes similar to those reported in Fawer et al. 

(Ref. 16), including Ngim et al. (Ref. 17) and Piikivi 

and Tolonen (Ref. 18). (See ATSDR, Ref. 14) EPA 

derived its RfC for chronic inhalation exposure to 

mercury vapor using the same occupational 

exposure study (Fawer et al., Ref. 16) and 

supporting studies (including Ngim et al. (Ref. 17) 

and Piikivi and Tolonen, (Ref. 18) used by ATSDR 

in deriving the MRL for chronic mercury vapor 

exposure (Ref. 15). EPA conducts periodic 

screening level reviews for chemicals and in 2002 

decided that the RfC for mercury vapor would 

remain unchanged (Ref. 15). 

10These ventilation rates were calculated as 

follows, using standard physiological parameters 

from several sources and handbooks (Refs. 19 and 

20) Adult: The tidal volume per kilogram body 

weight in adults is 10.7 mL/kg. The weight of the 

average adult is 70 kg. Given these two values, the 

tidal volume of the average adult is 750 mL. The 

respiratory rate of the average adult is 12–15 

breaths/minute. At a rate of 15 breaths/minute, the 

average adult would have a respiratory minute 

volume of 11.25 L/min. Given that there are 1,440 

minutes/day and 1 m3/1000 L, this would result in 

a ventilation rate of 16.2 m3/day. Five-year-old 

child: The tidal volume per kilogram body weight 

in five-year-old children is 10.7 mL/kg. The weight 

of the average five-year-old child is 20 kg. Given 

these two values, the tidal volume of the average 

five-year-old child is 217 mL. The respiratory rate 

of the average five-year-old child is 21–25 breaths/ 

minute. At a rate of 25 breaths/minute, the average 

five-year-old child would have a respiratory minute 

volume of 5.3 L/min. Given that there are 1440 

minutes/day and 1 m3/1000 L, this would result in 

a ventilation rate of 7.6 m3/day. One-year-old child: 

The tidal volume per kilogram body weight in oneyear-old children is 10 mL/kg. The weight of the 

average one-year-old child is 10 kg. Given these two 

values, the tidal volume of the average one-year-old 

child is 100 mL. The respiratory rate of the average 

one-year-old child is 40 breaths/minute. At a rate 

of 40 breaths/minute, the average one-year-old child 

would have a respiratory minute volume of 4 

L/min. Given that there are 1440 minutes/day and 

1. Review of Scientific Evidence 

As already noted, this rule and the 

special controls guidance reflect FDA’s 

evaluation of the valid scientific 

evidence related to the use of dental 

amalgam in the population age six and 

older and in potentially sensitive 

subpopulations (developing fetuses, 

breastfed infants, and children under 

age six). The White Paper (Ref. 10) and 

Addendum (Ref. 11) referenced in this 

rule include more details regarding 

FDA’s examination.4 These documents 

are included as references and are 

available on FDA’s Web site. 

In developing the White Paper and 

Addendum, FDA drew from the 

expertise of other groups 5 that had 

previously conducted reviews related to 

the potential health effects of dental 

amalgam. FDA’s approach was to build 

upon these reviews, rather than to 

duplicate the work other groups had 

already undertaken. FDA reviewed more 

than 200 scientific articles, published 

from 1997 to 2008, on the potential 

health effects of dental amalgam. In 

addition to considering these studies, 

FDA also considered information and 

assessments reviewed in the proposed 

rule, and other risk assessments 

developed since the publication of the 

proposed rule, including the 2004 Life 

Sciences Research Office (LSRO) Report 

(Ref. 13).6 In an effort to determine if 

any very recent articles would have an 

impact on FDA’s analysis, a literature 

search was conducted for 2008—July 

2009 (even though FDA had already 

reviewed studies published through 

October 2008). Three databases 

(PubMed, Biosis, and Embase) were 

searched with key words, such as 

mercury, toxicity, mercury vapor, 

adverse effect, dental, etc. Several 

studies from this search had already 

been reviewed in the FDA Addendum to 

the White Paper. After review of the 

total of 70 abstracts from the search, 

FDA determined that no studies have 

been published in 2008–2009 that 

would change FDA conclusions about 

the health effects of dental amalgam. 

FDA also considered the fact that 

dental amalgam is a commonly used 

device with a low frequency of adverse 

events reported to the Agency. FDA 

received 141 adverse event reports 

related to dental amalgam from 1988 to 

2008. It is estimated that over one 

billion amalgam restorations were 

placed during this time period. The 

majority of the dental amalgam adverse 

event reports submitted to FDA were 

anecdotal, lacked specific details, and 

were often reported years after 

placement of the restoration, making it 

difficult for the Agency to perform a 

causal analysis. 

An overview of the available evidence 

and FDA’s conclusions follows. 

a. Evidence Related to the Population 

Age Six and Older 

i. Air Monitoring Standards for 

Elemental Mercury Vapor 

The Agency for Toxic Substance and 

Disease Registry (ATSDR) has 

established a Minimal Risk Level 

(MRL) 7 for elemental mercury vapor at 

0.2 μg/m3. The Environmental 

Protection Agency (EPA) has established 

a Reference Concentration (RfC) 8 for 

elemental mercury vapor at 0.3 μg/m3. 

These reference values were derived 

using a standard risk assessment 

approach employing uncertainty factors, 

including an uncertainty factor to 

account for variability in sensitivity of 

the human population. They are 

considered to represent chronic or 

lifetime inhalation exposures that are 

free from adverse health outcomes and 

protective of human health for all 

individuals, including potentially 

sensitive populations such as children 

prenatally or postnatally exposed to 

mercury vapor (Refs. 14, 15).9

Using widely accepted values for the 

respiratory rate and tidal volume in 

individuals at various ages, the 

following ventilation rates were 

calculated: 16.2 m3/day for the average 

adult; 7.6 m3/day for the average fiveyear-old child; and 5.8 m3/day for the 

average one-year-old child.10

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1 m3/1000 L, this would result in a ventilation rate 

of 5.8 m3/day. 

11As described in Footnote 9, ATSDR used a total 

uncertainty factor of 30 to derive the MRL. 

12As discussed by EPA in their Staff Paper on 

Risk Assessment Principles and Practices, ‘‘EPA 

risk assessments tend towards protecting public and 

environmental health by preferring an approach 

that does not underestimate risk in the face of 

uncertainty and variability. In other words, EPA 

seeks to adequately protect public and 

environmental health by ensuring that risk is not 

likely to be underestimated.’’ See EPA 2004, An 

Examination of EPA Risk Assessment Principles 

and Practices, EPA/100/B–04/001 available at: 

http://www.epa.gov/osa/pdfs/ratf-final.pdf. 

13 Given that 50 μg Hg/g Cr is the threshold 

urinary mercury concentration associated with 

preclinical nervous and renal system effects, ACGIH 

recommends that the urinary mercury 

concentration of occupationally exposed 

individuals not exceed 35 μg Hg/g Cr. This urinary 

mercury concentration is associated with chronic 

occupational exposure of a healthy worker to an air 

concentration of 25 μg Hg/m3. 

At these ventilation rates, chronic 

exposure at the level of the MRL would 

result in an estimated dose of mercury 

vapor of 3.2 μg/day in the average adult, 

1.5 μg/day in the average five-year-old 

child, and 1.2 μg/day in the average oneyear-old child. Chronic exposure at the 

level of the RfC would result in an 

estimated dose of mercury vapor of 4.9 

μg/day in the average adult, 2.3 μg/day 

in the average five-year-old child, and 

1.7 μg/day in the average one-year-old 

child. 

ATSDR assumes a slightly higher 

ventilation rate of 20 m3/day for the 

average adult (Ref. 14). At this 

ventilation rate, chronic exposure at the 

level of the MRL would result in an 

estimated dose of elemental mercury 

vapor of 4 μg/day in the average adult. 

Chronic exposure at the level of the RfC 

would result in an estimated dose of 

elemental mercury vapor of 6 μg/day in 

the average adult. 

The U.S. Public Health Service (PHS) 

reviewed several studies estimating the 

daily dose of elemental mercury from 

dental amalgam (Ref. 3). In some of the 

studies, investigators measured the 

mercury concentration of intraoral and 

exhaled air in small populations of 

individuals with and without amalgams. 

In these studies, estimates of the daily 

dose of mercury from dental amalgams 

ranged from 1–29 μg/day. However, the 

reliability of these studies is 

questionable. Problems have been cited 

with the instruments used to measure 

mercury vapor in the oral cavity. 

Questions have also been raised about 

whether the small size of the oral cavity 

is appropriate for accurately measuring 

vapor concentrations, and about how to 

control for variable factors such as the 

dilution of vapor with inhaled air 

within the oral cavity and inhalation/ 

exhalation rates, analytical quality 

control, and differences in sampling 

methodology (Ref. 20). According to 

PHS, the best estimates of daily intake 

of mercury from dental amalgam 

restorations have come from 

measurements of mercury in blood 

among subjects with and without 

amalgam restorations, and subjects 

before and after amalgams were 

removed. For adults, these estimates 

range from 1–5 μg/day. 

The World Health Organization 

(WHO) also reviewed several studies 

estimating the daily dose of elemental 

mercury from dental amalgam (Ref. 21). 

WHO found that values generally in the 

range of 1–5 μg/day were estimated in 

the U.S. adult population, which is 

consistent with the PHS determination. 

WHO noted three studies that made 

higher estimates of the daily dose. The 

highest estimate that WHO reports was 

a dose of 12 μg/day, for middle-aged 

individuals with approximately 30 

amalgam surfaces (Ref. 22). 

According to these estimates, the 

daily dose of mercury from dental 

amalgam is generally expected to be in 

the same range as the daily dose that 

would result from chronic exposure at 

the level of the MRL (4 μg/day) or the 

RfC (6 μg/day) in adults. Moreover, 

exceeding these protective reference 

levels does not necessarily mean that 

any adverse effects will occur (Refs. 14– 

15). FDA assumes that the daily dose 

from amalgam in children under six 

years old is below those in adults since 

children under six years old have fewer 

and smaller teeth and lower ventilation 

rates as compared to adults. 

Given that the MRL and the RfC were 

derived to be protective and are set 

below air mercury concentrations 

associated with observed adverse health 

effects,11 chronic exposure at these 

levels would not generally be expected 

to produce such effects. Chronic 

exposure to air mercury concentrations 

several times higher than the MRL and 

the RfC would also generally not be 

expected to result in adverse effects, 

because of the conservative approach of 

incorporating uncertainty factors in the 

derivation of these reference levels.12

Moreover, both the MRL and the RfC 

assume lifetime chronic exposure. FDA 

has taken a conservative approach by 

applying these reference levels to 

children, who have experienced less 

than a full lifetime of exposure. 

ii. Biological Monitoring Standards for 

Urine Mercury 

Occupational Studies 

Several studies have assessed the risk 

of adverse health effects in workers 

occupationally exposed to high doses of 

mercury vapor. Strong correlations have 

been found between daily, timeweighted air concentrations, adverse 

health outcomes, and urinary mercury 

levels in workers (Refs. 14, 21). 

Based on a number of occupational 

studies, the American Conference of 

Government Industrial Hygienists 

(ACGIH) has determined that the 

biological threshold for preclinical 

changes for central nervous system and 

kidney effects is 50 μg Hg/g Cr (Ref. 

24).13 However, occupational studies 

published since 1996 report that 

increases in urinary levels of early 

biomarkers predictive of renal injury 

have been observed at urinary mercury 

concentrations of 16–28 μg Hg/g Cr 

(Refs. 25–28). 

Studies of Amalgam Bearers 

Studies of large cohorts indicate that 

urinary mercury concentrations in 

individuals without dental amalgam 

restorations are approximately 0.5–0.6 

μg Hg/g Cr in adults (Refs. 29, 30) and 

0.5–2 μg Hg/g Cr in children, aged 6–17 

(Refs. 31, 32). 

Studies of adults with dental amalgam 

restorations have found a positive 

correlation between the number of 

dental amalgam restorations in the 

mouth and urinary mercury 

concentration. In a study of 1,626 

women, aged 16–49, urinary mercury 

concentrations ranged from 0.83–1.25 μg 

Hg/g Cr (Ref. 29). The average urinary 

mercury concentration for the 75 

percent of the women who had 12 

amalgam surfaces or less was reported 

to be 0.81 μg Hg/g Cr. In a study of 550 

adults, aged 30–49, urinary mercury 

concentrations ranged from 0.75–2.9 μg 

Hg/g Cr in individuals with 1–46 

amalgam surfaces (Ref. 33). In one study 

of 1,127 men, aged 40–78, with dental 

amalgam restorations, 47 percent of the 

participants had a urinary mercury 

concentration less than 1.5 μg Hg/g Cr, 

and 1.3 percent of the participants had 

urinary mercury concentrations over 12 

μg Hg/g Cr (Ref. 30). A urinary mercury 

concentration of 1.9 μg Hg/g Cr was 

reported for men with approximately 20 

amalgam surfaces. Based on the study’s 

analysis, an individual with 60 amalgam 

surfaces would be expected to have a 

urinary mercury concentration of 4–5 μg 

Hg/g Cr. 

Studies have also assessed urinary 

mercury concentrations in amalgambearing children age six or older. Two 

prospective studies assessed urinary 

mercury concentrations in children age 

six and older after placement of dental 

amalgam restorations. In a seven-year 

study of children ages eight to ten at 

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14The authors noted that ‘‘[w]hen summarizing 

the available evidence, one could suggest that longterm neurobehavioral effects on a group basis may 

occur when the average [urinary mercury] 

concentration has been in the range of 30–40 nmol/ 

mmol Cr [53.1–70.8 μg Hg/g Cr] or higher, but not 

when the average [urinary mercury] concentration 

has been lower than 10 nmol/mmol Cr [17.7 μg Hg/ 

g Cr].’’ 

baseline, the highest average urinary 

mercury concentration reported during 

the study period was 3.2 μg Hg/g Cr 

(Ref. 31); this level occurred during the 

second year of the follow-up and 

progressively declined through year 

seven. The subjects had an average total 

of 19 amalgam surfaces at the end of the 

study period. In a five-year study of 

children ages six to ten at baseline, 

average urinary mercury concentrations 

were 0.9 μg Hg/g Cr (range 0.1–5.7) five 

years after dental amalgam placement 

(Ref. 34). The subjects had an average 

total of 12 amalgam surfaces at the end 

of the study period. The highest outlier 

in this study had a reported urinary 

mercury concentration of 10.5 μg Hg/g 

Cr. Children from the composite 

restoration-only group averaged 0.6 μg 

Hg/g Cr (range 0.1–2.9). In a study of 60 

children aged 4–8 years (Ref. 89), those 

with amalgam restorations had higher 

urinary mercury concentrations (1.4 μg 

Hg/g Cr) compared to those without 

amalgams (0.436 μg Hg/g Cr). 

The urinary mercury concentrations 

generally observed in adults and 

children age six and older with dental 

amalgam restorations is approximately 

one order of magnitude less than the 

threshold levels associated with 

preclinical neurological and renal 

health effects in persons occupationally 

exposed to mercury vapor. Reported 

high outliers in adults and children age 

six and older are also below this 

threshold level. 

FDA has concluded that exposures to 

mercury vapor from dental amalgam do 

not put individuals age six and older at 

risk for mercury-associated adverse 

health effects. 

iii. Clinical Studies 

In order to assess potential health 

effects of mercury exposure from dental 

amalgam in the population age six and 

older, FDA reviewed studies evaluating 

neurological and renal outcomes. 

Studies of persons occupationally 

exposed to mercury vapor are also 

helpful for assessing risks of potential 

toxicity in the population age six and 

older from exposure to mercury vapors 

released from dental amalgams because 

occupationally-exposed individuals are 

exposed to higher mercury levels than 

those associated with dental amalgams. 

Neurological Effects 

Occupational Studies 

In a study of chloralkali workers and 

age-matched controls evaluated twice at 

five years apart, no correlations were 

found between multiple 

neurobehavioral (motor and cognitive) 

and tremor tests and mercury vapor 

exposure (Ref. 35). Performance on only 

one test, the Digital Symbol Test, 

showed improvement when subjects 

were tested five years later after 

exposure ceased suggesting that these 

individuals experienced some 

neurological toxicity while still being 

exposed to mercury at the time of the 

initial testing. Those subjects who 

demonstrated improvement had the 

highest inorganic mercury blood 

concentrations.14

In another study, 38 chloralkali 

workers with average urinary mercury 

concentration of 9 μg Hg/g Cr were 

compared with non-exposed controls 

(average urinary mercury concentration 

2 μg/g Cr (Ref. 36)). No differences in 

results of multiple neurobehaviorial 

tests were observed between the two 

groups. 

Studies of Amalgam Bearers 

Studies have shown a lack of 

association between amalgam exposure 

and neuropsychological and 

neurobehavioral deficits. In a 

retrospective study of 550 adults, no 

significant associations between 

neuropsychological function and 

indices of cumulative amalgam 

exposure over many years were found 

(Ref. 33). In a report evaluating 1,127 

men (Ref. 37), no effects on tremor, 

coordination, gait, strength, sensation, 

muscle stretch, or peripheral 

neuropathy were associated with 

amalgam exposure. 

It has been suggested that exposure to 

mercury vapor from dental amalgam 

may be linked to various neurological or 

neurodegenerative diseases, such as 

Parkinson’s disease, Alzheimer’s 

disease, multiple sclerosis, amyotrophic 

lateral sclerosis, and autism. There is a 

paucity of studies that evaluate a link 

between dental amalgam and these 

conditions. 

In one study, regional brain levels of 

mercury were determined at autopsy in 

subjects with Alzheimer’s disease and 

controls (Ref. 38). Brain mercury levels 

did not correlate with the number of 

amalgams and there were no differences 

between the Alzheimer’s disease and 

control groups with respect to number 

of amalgams. In another study, the mean 

number of dental amalgam surfaces and 

urinary mercury concentrations for 

Alzheimer’s disease patients were not 

different from those of control patients 

(Ref. 39). In a study of aging and 

Alzheimer’s disease evaluating 129 

Catholic nuns, aged 75–102, no effect of 

dental amalgam number and surfaces 

was observed for eight tests of cognitive 

function (Ref. 38). These findings do not 

support the hypothesis that mercury 

from dental amalgam plays a role in the 

pathogenesis of Alzheimer’s disease. 

Several reports of results from 

prospective clinical studies of dental 

amalgam numbers (Refs. 31, 32, 34, and 

40) found no neurological deficits in 

children who first received dental 

amalgam restorations at ages six to ten 

and were followed for five or seven 

years. 

FDA concludes that the existing data 

support a finding that exposures to 

mercury vapor at levels associated with 

dental amalgams do not result in 

neurological deficits, tremors, 

peripheral neuropathies, or Alzheimer’s 

Disease in the population age six and 

older. Although the existing clinical 

data on purported links between dental 

amalgam and other neurological or 

neurodegenerative diseases, such as 

Parkinson’s Disease are limited, FDA 

concludes that, in light of the air 

monitoring and biological monitoring 

evidence described above, there is 

information from which to determine 

that general and special controls are 

sufficient to provide a reasonable 

assurance of safety and effectiveness. 

Renal Effects 

The kidneys accumulate the highest 

organ concentration of mercury (as 

Hg 2+) following exposure to mercury 

vapor. The concentration of mercury in 

the kidney has been associated with the 

number of dental amalgams (Refs. 41, 

42). 

Animal Studies 

Renal mercury concentrations 

increased in proportion to increasing 

mercury vapor exposure concentrations 

in rats (Refs. 43, 44). Pregnant rats 

exposed to high concentrations of 

mercury vapor through gestation 

exhibited increases in two biomarkers of 

renal injury at gestation day 15, but no 

changes were observed for three other 

biomarkers at any time evaluated during 

gestation (Ref. 44). 

Occupational Studies 

Numerous occupational studies of 

mercury vapor exposure indicate that 

effects on the kidney begin to manifest 

when urinary mercury concentrations 

reach or exceed 50 μg Hg/g creatinine 

(Ref. 24). However, occupational studies 

published since 1996 report that 

increases in urinary levels of early 

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biomarkers predictive of renal injury 

have been observed at urinary mercury 

concentrations of 16–28 μg Hg/g 

creatinine. In a study of chloralkali 

workers exposed to mercury vapor for 

13 years (mean urinary mercury 

concentrations of 16.5 μg/g Cr), no 

significant differences in urinary 

biomarkers of renal function were found 

between the exposed and non-exposed 

groups (Ref. 45). Urinary biomarkers of 

renal function may be reversible upon 

cessation of exposure at the levels of 

exposure in this study. In several 

occupational studies of exposed workers 

(Refs. 25–28), increases in urinary Nacetylglucosamindase (NAG), a 

preclinical renal biomarker, were 

correlated with urinary mercury 

concentrations of 16–28 μg Hg/g Cr. In 

another study, 38 chloralkali workers 

with average urinary mercury 

concentration of 9 μg Hg/g Cr were 

compared with non-exposed controls 

(average urinary mercury concentration 

2 μg Hg/g Cr (Ref. 36)). No differences 

in renal expression as measured by 

multiple preclinical urinary biomarkers 

were observed between the two groups. 

Studies of Amalgam Bearers 

Two prospective amalgam trials in 

children age six and older demonstrated 

that kidney injury is not associated with 

exposure to dental amalgam. In the New 

England trial (Ref. 46) groups of 

children had amalgam or composite 

restorations placed at ages 6–8 and were 

followed for 5 years. Results showed 

that, although microalbuminuria levels 

were higher in the amalgam treatment 

group, the levels of three other 

biomarkers of kidney injury were not 

different between the amalgam versus 

composite restoration groups. The 

authors of the study noted that they 

were unable to determine whether the 

increase in microalbuminuria was 

related to treatment or may have 

occurred by chance, since albuminuria 

may be caused by strenuous physical 

exercise, urinary tract infections, or 

other conditions with fever, or be 

related to orthostatic proteinuria (Ref. 

46). In another children’s prospective 

trial (Casa Pia), groups of children had 

amalgam or composite restorations 

placed at ages 6–10 and were followed 

for 7 years. There were no differences 

between the amalgam and composite 

groups with respect to the urinary 

excretion of microalbumin or albumin 

(Ref. 31), a biomarker of renal 

glomerular injury, and GST-alpha and 

GST-pi, two biomarkers of renal 

proximal and distal tubule injury, 

respectively (Ref. 47). 

FDA concludes that the data from 

these studies support a finding that 

exposures to mercury vapor at levels 

associated with dental amalgams do not 

result in renal damage in the population 

age six and older. The conclusions from 

studies of amalgam mercury exposure 

and neurological and renal endpoints 

are supported by independent 

investigations by other scientific bodies, 

such as the European Commission’s 

Scientific Committee on Emerging and 

Newly Identified Health Risks 

(SCENIHR), which stated in 2007 that 

‘‘no risks of adverse systemic effects 

exist and the current use of dental 

amalgam does not pose a risk of 

systemic disease’’ (Ref. 6). 

In light of the evidence from air 

monitoring, biological monitoring, and 

clinical studies, FDA concludes that 

exposures to mercury vapor from dental 

amalgam are not associated with 

adverse health effects in the population 

age six and older. 

b. Evidence Related to Special 

Populations 

i. Potentially Sensitive Subpopulations 

(Developing Fetuses, Breastfed Infants, 

and Children Under Age Six) 

Fetal Development 

Elemental mercury is transported 

through the placenta, which results in 

fetal exposure with the potential for 

subsequent developmental toxicity in 

offspring. 

Animal Studies 

FDA reviewed several well-conducted 

studies designed to assess high-level 

mercury vapor exposure on 

developmental effects in pregnant 

animals and their offspring. High levels 

of maternal mercury vapor exposure 

were associated with the accumulation 

of mercury in fetal tissues. In one study 

(Ref. 48), no effects were observed on 

peripheral, somatosensory, auditory, or 

visual neurological functions in 

offspring of rats exposed to mercury 

vapor prenatally. In another study, 

prenatal exposure of pregnant rats was 

associated with adverse effects on fetal 

development only in cases where 

maternal exposure to mercury vapor 

was so high that it became toxic to the 

mother (leading to decreased maternal 

body weight, which can directly alter 

fetal development) (Ref. 44). The 2004 

Life Sciences Research Office (LSRO) 

Report (Ref. 13) reviewed several 

studies of exposure of pregnant squirrel 

monkeys to high concentrations of 

mercury vapor. Although mercury 

accumulated in brain tissues in utero, 

only modest effects were observed on 

learning, motor function, and adaptive 

behaviors. In all of the aforementioned 

studies, maternal mercury vapor 

exposures were considerably higher 

than those estimated for individuals 

with dental amalgam restorations. 

Occupational Studies 

Very few available studies have 

evaluated the effects of elemental 

mercury exposure on pregnancy 

outcomes in humans. Although mercury 

has the ability to cross the placental 

barrier, the limited human data do not 

demonstrate an association between 

exposure to the mercury in dental 

amalgam and adverse reproductive 

outcomes such as low birth weight 

babies or increased rates of miscarriage. 

In a retrospective study (Ref. 49), no 

strong association or clear doseresponse relationship between 

occupational exposure to chemical 

agents or restorative materials and the 

risk of miscarriage was observed. A 

slight but non-significant increase in 

risk was found for exposure to some 

acrylate compounds, mercury amalgam, 

solvents and disinfectants leading the 

authors to conclude that they could not 

rule out the possibility of a slightly 

increased risk of miscarriage among 

exposed dental workers. In a study of 

female factory workers exposed to a 

median concentration of 90 μg Hg/m3

(maximum 600 μg/m3), no significant 

differences in stillborn or miscarriage 

rates were observed between exposed 

and unexposed subjects (Ref. 50). The 

mercury vapor concentrations to which 

these workers were exposed were over 

an order of magnitude higher than those 

associated with dental amalgam. 

Studies in Amalgam Bearers 

Very few well-controlled animal 

studies or human epidemiological 

studies have evaluated the potential 

effect of low-level mercury vapor 

exposure on fetal development, 

especially at exposures experienced by 

dental amalgam bearers. In one 

retrospective study (Ref. 51), no 

association was found between the 

number of amalgam fillings in women 

and low birth weight of their babies. 

However, there is limited clinical 

information concerning the effects of 

prenatal exposure from maternal 

sources of mercury vapor at relevant 

concentrations. 

Although the data are limited, FDA 

concludes that the existing data do not 

suggest that fetuses are at risk for 

adverse health effects due to maternal 

exposure to mercury vapors from dental 

amalgam. As described earlier in this 

document, maternal exposures are likely 

to increase temporarily when new 

dental amalgams are inserted or existing 

dental amalgam restorations are 

removed. 

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15EPA defines a Reference Dose (RfD) as follows: 

‘‘An estimate (with uncertainty spanning perhaps 

an order of magnitude) of a daily oral exposure to 

the human population (including sensitive 

subgroups) that is likely to be without an 

appreciable risk of deleterious effects during a 

lifetime. It can be derived from a NOAEL [no 

observed adverse effect level], LOAEL [lowest 

observed adverse effect level], or benchmark dose, 

with uncertainty factors generally applied to reflect 

limitations of the data used’’ (http://www.epa.gov/ 

ncea/iris/help_gloss.htm#r). 

16Table 4 of this final rule (section V), ‘‘Projected 

Amalgam Restorations for Specific Populations’’ 

projects for 2009 that total amalgam in children 

under age 6 will be 2.6 million. 

Breastfed Infants 

Mercury present in the mother’s body 

is transmitted to her infant through 

breast milk. Maternal exposure to 

elemental mercury vapor would be 

expected to affect the concentration of 

inorganic mercury in breast milk. 

The EPA has set a Reference Dose 

(RfD) 15 for oral exposure to inorganic 

mercury at 0.3 μg Hg/kg/day (Ref. 52). 

This value represents the daily exposure 

to inorganic mercury that is likely to be 

without an appreciable risk of 

deleterious health effects during a 

lifetime. Reference values are derived to 

be protective against adverse health 

effects in sensitive subpopulations, such 

as developing fetuses and children. 

Seven studies reviewed in the 2004 

Life Sciences Research Office Report 

evaluated concentrations of total 

mercury in breast milk. In some of the 

reviewed studies, the number of 

amalgams correlated with the 

concentration of total mercury in breast 

milk (Refs. 53, 54, 55). However, the 

LSRO report concluded from its review 

that inorganic mercury absorption 

through breast milk is not a significant 

source of mercury exposure to infants 

(Ref. 13). 

One study (Ref. 56) determined the 

concentration of breast milk mercury 

attributable to dental amalgam. In this 

study, the concentration of mercury in 

subjects with dental amalgam 

restorations was subtracted from the 

level in subjects without dental 

amalgam restorations. The level of 

mercury attributable to amalgam was 

0.09 μg Hg/L (Addendum, p. 13). A 

standard value used in risk assessment 

for daily breast milk consumption is 

0.85 L/day. Based on this value, the 

typical daily dose of inorganic mercury 

from breastfeeding in an individual with 

dental amalgam restorations would be 

0.075 μg Hg/day. For a 5 kg infant, the 

daily exposure to inorganic mercury 

from breastfeeding would be 0.015 μg 

Hg/kg/day. 

The estimated concentration of 

mercury in breast milk attributable to 

dental amalgam exposure is low and is 

an order of magnitude below the healthbased exposure reference value for oral 

exposure to inorganic mercury 

established to protect the health of 

adults and children. 

FDA concludes that the existing data 

support a finding that infants are not at 

risk for adverse health effects from the 

breast milk of women exposed to 

mercury vapors from dental amalgams. 

Children Under Six Years of Age 16

No clinical studies have evaluated the 

effects of mercury vapor exposure from 

dental amalgam in children under six 

years of age. FDA assumes that the daily 

dose of mercury from amalgams in 

children less than six years old would 

not be higher than the estimated daily 

dose for adults (1–5 μg/day). FDA 

expects that the daily dose in children 

will be lower than the estimated dose 

for adults since children less than six 

have fewer and smaller teeth and lower 

ventilation rates, as compared to adults. 

The MRL and the RfC are derived using 

a conservative approach by applying 

uncertainty factors, and therefore are 

protective against adverse health effects, 

in populations including potentially 

sensitive subpopulations such as young 

children. Therefore, chronic exposure at 

these or slightly higher levels would not 

generally be expected to produce 

adverse health effects, suggesting that 

these children are not at risk for adverse 

health effects from mercury vapor 

released from dental amalgams. 

Summary 

Based on comparisons between the 

expected daily dose in these potentially 

sensitive subpopulations and the MRL 

and RfC, the exposure estimated from 

breast milk in breastfed infants, and 

clinical studies, we would not expect to 

see any adverse health effects in these 

subpopulations from mercury vapors 

released from dental amalgam. 

However, the data regarding risk in 

these subpopulations is not as robust as 

in adults due to the absence of 

measured urinary mercury 

concentrations and limited clinical data 

in these subpopulations. 

ii. Dental Professionals 

Dentists and their staff may be 

exposed to mercury vapor in the 

workplace during the preparation, 

placement, and removal of dental 

amalgams. As noted by the Dental 

Products Panel, improper use of dental 

amalgam exposes dental professionals to 

risks associated with mercury toxicity. 

Improper storage, trituration, and 

handling contribute to this risk (Ref. 1). 

Dental professionals are generally 

exposed to lower levels of mercury 

vapor than those that have been 

reported in industrial settings, and they 

have urinary mercury concentrations 

approaching those observed in nonoccupationally-exposed populations. 

Several studies, primarily from one 

laboratory group, provide the most 

information about the potential health 

effects of low-level mercury exposure 

among dental professionals. In four of 

these studies, mean urinary mercury 

concentrations in dentists and 

hygienists ranged from 0.9 to 3 μg Hg/ 

L (∼0.7 to 2.3 μg Hg/g Cr) and were 

associated with some neurobehavioral 

effects. In a fourth study which pooled 

results from six earlier studies, urine 

mercury concentrations ranged from 

less than 1 μg Hg/L (∼0.8 μg Hg/g Cr) to 

greater than 50 μg Hg/L (∼38μg Hg/g Cr). 

A significant weakness of these studies 

was that no non-mercury-exposed 

dental professionals were evaluated; 

therefore, the effect of exposure to other 

chemicals in the workplace (gases, 

organic solvents) cannot be ruled out. 

Nor was a non-dental workplace control 

group studied, which would have been 

informative about effects of the dental 

work environment in general. The 

neurobehavioral measures reported in 

several studies of dentist/dental 

assistant populations as being 

significantly correlated with mercury 

exposure (urine mercury levels) have 

not been shown in some cases to be 

similarly affected in other 

occupationally-exposed groups where 

urinary mercury concentrations were 

much higher (e.g., chloralkali workers) 

than in the dental professional cohorts. 

In one study (Ref. 57), 34 dentists and 

15 hygienists exposed to mercury vapor 

in the workplace (mean number of 

amalgams placed was 16.1) were 

chelated to allow assessment of recent 

mercury exposure (pre-chelation) and 

body burden from longer-term 

exposures (post-chelation). Mean 

urinary mercury concentrations for each 

group were: 0.9 ± 0.5 μg Hg/L (0.7 μg 

Hg/g Cr) before chelation; 9.1 ± 6.9 μg 

Hg/L (7 μg Hg/g Cr) after chelation. 

Subtle but statistically significant 

associations were demonstrated for 

recent exposure (pre-chelation) and 

measures of mood, motor function and 

cognition, and mercury body burden 

(post-chelation) was associated with 

symptoms, mood, and motor function. 

Chelation of mercury in dental 

professionals suggests that the mercury 

body burden in this population of 

workers is much greater than indicated 

solely by pre-chelation urinary mercury 

levels. 

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17 Dental Amalgam: A Scientific Review and 

Recommended Public Health Service Strategy for 

Research, Education and Regulation; Public Health 

Service, U.S. Department of Health and Human 

Services, January 1993. 

18Liu, J. et al., ‘‘Toxic effects of metals,’’ Casarett 

& Doull’s Toxicology: The Basic Science of Poisons, 

Chapter 23, pp. 931–979, McGraw-Hill Medical, 

New York, New York, 2008. 

Clarkson, T.W. et al., ‘‘The Toxicology of Mercury 

and Its Chemical Compounds,’’ Critical Reviews in 

Toxicology, Vol. 36, pp. 609–662, 2006. 

19 De Rouen, T. et al., ‘‘Neurobehavioral Effects of 

Dental Amalgam in Children, A Randomized 

Clinical Trial,’’ Journal of the American Medical 

Association, Vol. 295, 1784–1792, No. 15, April, 19, 

2006. 

Continued 

Another study (Ref. 58) 230 dentists 

(data pooled from six previous studies) 

had urinary mercury concentrations 

ranging from less than 1 μg Hg/L (∼0.8 

μg Hg/g Cr) to greater than 50 μg Hg/L 

(∼38 μg Hg/g Cr); 50% subjects had 

urine concentrations less than 3 μg Hg/ 

L (∼2 μg Hg/g Cr) and 30% had 

concentration greater than 20 μg Hg/L 

(∼15 μg Hg/g Cr). Dentists stratified into 

three urine mercury concentration 

groups: Less than 1 μg Hg/L (∼0.8 μg Hg/ 

g Cr), 1–20 μg Hg/L (∼0.8–15 μg Hg/g Cr) 

and greater than 20 μg Hg/L (∼15 μg Hg/ 

g Cr). An association of urine mercury 

concentrations to a hand steadiness test 

was highly significant; however, 

associations with motor function tests 

were not significant. 

Two studies (Refs. 59, 60) evaluated 

194 dentists (average exposure of 26 

years; average amalgam surfaces = 16; 

urine mercury = 3.32 ± 4.87 μg/L, ∼2.6 

μg/g Cr) and 233 hygienists (average 

exposure of 15 years; average amalgam 

surfaces = 12; urine mercury = 1.98 ± 

2.29 μg/L, ∼1.48 μg/g Cr) for 

neurological effects. No effects were 

observed on verbal intelligence and 

reaction time. Significant correlations 

with urine mercury concentrations were 

found on 9 measures in dentists and 8 

measures in hygienists, including visual 

discrimination, hand steadiness, finger 

tapping and trail making tests. A 

weakness of the study was that no nonmercury-exposed dental professionals 

were studied; therefore, the effect of 

exposure to other chemicals in the 

workplace (gases, organic solvents) 

cannot be ruled out. Nor was a nondental workplace control group studied, 

which would have been informative 

about effects of the dental work 

environment in general. 

FDA concludes that existing data 

indicate that dental professionals are 

generally not at risk for mercury toxicity 

except when dental amalgams are 

improperly used, stored, triturated, or 

handled. 

iii. Individuals With Mercury Allergies 

Some individuals are hypersensitive 

or allergic to mercury and/or other 

metals. FDA reviewed several 

epidemiological and case studies related 

to the effects of mercury vapor exposure 

from dental amalgam on allergic 

individuals. 

According to some of the studies that 

were reviewed, some patients develop 

adverse tissue reactions such as 

dermatological conditions or lesions of 

the skin, mouth, and tongue as a result 

of exposure to dental amalgam (Ref. 61, 

62). In mercury-allergic individuals, 

clinical improvements were reported 

after dental amalgam restorations were 

removed. Other studies reported that 

dental amalgam may exacerbate preexisting autoimmune disease in 

mercury-allergic individuals (Refs. 63, 

64). After dental amalgam restorations 

were removed, the health status of these 

patients reportedly improved. 

FDA concludes that existing data 

indicate that certain individuals with a 

pre-existing hypersensitivity or allergy 

to mercury may be at risk for adverse 

health effects from mercury vapor 

released from dental amalgam. 

2. Rationale for Special Controls 

In light of the above information, FDA 

has identified the following as the 

potential risks to health associated with 

the use of dental amalgam devices, 

requiring the establishment of special 

controls: (1) Exposure to mercury; (2) 

allergic response including adverse 

tissue reaction; (3) contamination; (4) 

mechanical failure; (5) corrosion; and 

(6) improper use. FDA is establishing a 

special controls guidance document that 

includes recommendations to address 

these risks as follows. 

a. Risk of Exposure to Mercury 

As discussed above, dental amalgam 

releases mercury vapor and is associated 

with a risk of human exposure to this 

vapor. The special controls to address 

this risk are recommendations for: (i) 

Specific labeling, (ii) an information for 

use statement, and (iii) a performance 

test for mercury vapor release. 

i. Specific Labeling Recommendation 

The special controls guidance 

recommends the following specific 

labeling: 

• WARNING: CONTAINS MERCURY. 

• Warning: May be harmful if vapors 

are inhaled. 

• Precaution: Use with adequate 

ventilation. 

• Precaution: Store in a cool, well 

ventilated place. 

• Contains [ ]% mercury by weight. 

The recommended warning about the 

presence of mercury in a dental 

amalgam device and the recommended 

disclosure of mercury content by weight 

will alert dental professionals of the 

potential for exposure to mercury vapor 

and will remind them of the need for 

protective measures, such as the use of 

gloves when handling the device. The 

recommended precautions about the 

need for adequate ventilation and the 

need to store in a cool, well ventilated 

place will encourage professionals to 

ensure there is adequate ventilation 

when in proximity to the device and to 

use a vacuum pump and adequate 

ventilation during placement of dental 

amalgams to minimize the amount of 

mercury vapor that they or their patients 

may inhale. 

ii. Information for Use Recommendation 

Dental amalgam has been and remains 

one of the most commonly used 

restorative materials in dentistry. In the 

recent past the use of dental amalgam 

has gradually declined due to the 

improved properties of composite resin 

materials. Although amalgam has been 

used successfully for many years, the 

risks associated with this device have 

been controversial. Some scientists, 

professional groups, clinicians and 

patient advocacy groups have expressed 

concern about the potential hazards to 

health arising from mercury vapor 

release from amalgam restorations. 

Other groups of scientists, clinicians, 

and professional organizations have 

disagreed with these concerns. These 

opposing viewpoints were voiced at the 

2006 FDA joint panel meeting (Ref. 66). 

In order for dentists to make 

appropriate treatment decisions with 

their patients, it is important to provide 

information to help dentists understand 

the complexities of the science related 

to dental amalgam and its mercury 

content. 

FDA recommends the inclusion of an 

‘‘information for use’’ statement in 

dental amalgam labeling as a special 

control: 

Dental amalgam has been demonstrated to 

be an effective restorative material that has 

benefits in terms of strength, marginal 

integrity, suitability for large occlusal 

surfaces, and durability.17 Dental amalgam 

also releases low levels of mercury vapor, a 

chemical that at high exposure levels is welldocumented to cause neurological and renal 

adverse health effects.18 Mercury vapor 

concentrations are highest immediately after 

placement and removal of dental amalgam 

but decline thereafter. 

Clinical studies have not established a 

causal link between dental amalgam and 

adverse health effects in adults and children 

age six and older. In addition, two clinical 

trials in children aged six and older did not 

find neurological or renal injury associated 

with amalgam use.19

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Bellinger, D.C. et al., ‘‘Neuropsychological and 

Renal Effects of Dental Amalgam in Children: A 

Randomized Clinical Trial,’’ Journal of the 

American Medical Association, Vol. 295, No. 15, 

April 19, 2006, 1775–1783, 2006. 

Barregard, L. et al., ‘‘Renal Effects of Dental 

Amalgam in Children: The New England Children’s 

Amalgam Trial,’’ Environmental Health 

Perspectives, Volume 116, 394–399, No. 3, March 

2008. 

Woods, J.S. et al., ‘‘Biomarkers of Kidney 

Integrity in Children and Adolescents with Dental 

Amalgam Mercury Exposure: Findings from the 

Casa Pia Children’s Amalgam Trial,’’ Environmental 

Research, Vol. 108, pp. 393–399, 2008. 

Lauterbach, M. et al., ‘‘Neurological Outcomes in 

Children with and Without Amalgam-Related 

Mercury Exposure: Seven Years of Longitudinal 

Observations in a Randomized Trial,’’ Journal of the 

American Dental Association, Vol. 139, 138–145, 

February 2008. 

20Agency for Toxic Substances and Disease 

Registry (ATSDR) and Research Triangle Institute, 

Toxicological profile for mercury, U.S. Dept. of 

Health and Human Services, Public Health Service, 

Atlanta, Georgia, 1999. 

United States Environmental Protection Agency 

(EPA), ‘‘Integrated Risk Information System (IRIS) 

Screening-Level literature Review’’—Mercury, 

elemental, 2002. 

21 Dental amalgam devices currently on the 

market must also be in conformance with the 

special controls guidance. 

The developing neurological systems in 

fetuses and young children may be more 

sensitive to the neurotoxic effects of mercury 

vapor. Very limited to no clinical information 

is available regarding long-term health 

outcomes in pregnant women and their 

developing fetuses, and children under the 

age of six, including infants who are 

breastfed. 

The Agency for Toxic Substances and 

Disease Registry’s (ATSDR) and the 

Environmental Protection Agency (EPA) have 

established levels of exposure for mercury 

vapor that are intended to be highly 

protective against adverse health effects, 

including for sensitive subpopulations such 

as pregnant women and their developing 

fetuses, breastfed infants, and children under 

age six.20 Exceeding these levels does not 

necessarily mean that any adverse effects will 

occur. 

FDA has found that scientific studies using 

the most reliable methods have shown that 

dental amalgam exposes adults to amounts of 

elemental mercury vapor below or 

approximately equivalent to the protective 

levels of exposure identified by ATSDR and 

EPA. Based on these findings and the clinical 

data, FDA has concluded that exposures to 

mercury vapor from dental amalgam do not 

put individuals age six and older at risk for 

mercury-associated adverse health effects. 

Taking into account factors such as the 

number and size of teeth and respiratory 

volumes and rates, FDA estimates that the 

estimated daily dose of mercury in children 

under age six with dental amalgams is lower 

than the estimated daily adult dose. The 

exposures to children would therefore be 

lower than the protective levels of exposure 

identified by ATSDR and EPA. 

In addition, the estimated concentration of 

mercury in breast milk attributable to dental 

amalgam is an order of magnitude below the 

EPA protective reference dose for oral 

exposure to inorganic mercury. FDA has 

concluded that the existing data support a 

finding that infants are not at risk for adverse 

health effects from the breast milk of women 

exposed to mercury vapors from dental 

amalgam.’’ 

The purpose of this labeling 

recommendation is address potential 

misunderstandings about the risk of 

exposure to mercury from the device 

and to help dental professionals plan 

appropriate treatment recommendations 

for their patients by providing them 

with FDA’s assessment of the most 

current, best available evidence 

regarding potential risks to health from 

mercury vapor released from dental 

amalgams. 

iii. Performance Test Recommendation 

The special controls guidance 

recommends a performance test to 

determine the amount of mercury vapor 

released by a dental amalgam device 

during corrosion (ng/cm2 in 4 hrs). 

Dental amalgam releases the highest 

levels of mercury vapor when it 

corrodes (Ref. 65). By measuring the 

amount of mercury vapor released 

during corrosion, the recommended 

performance test will quantify the 

highest levels of vapor release that can 

be expected from a dental amalgam 

device. The results of this test will 

enable FDA, through a premarket 

notification (510(k)) submission, to 

determine if these levels are acceptable 

and are comparable to legally marketed 

devices.21

b. Risk of Allergic Response Including 

Adverse Tissue Reaction 

Dental amalgam is associated with a 

risk of adverse tissue reaction, 

particularly in individuals with a 

mercury allergy, who may experience 

additional allergic reactions. The special 

controls to address this risk are 

recommendations for: (i) Specific 

labeling and (ii) a performance test for 

biocompatibility. 

i. Specific Labeling Recommendation 

The special controls guidance 

recommends the following specific 

labeling: 

0 Contraindication: Do not use in 

persons with a known mercury allergy. 

The recommended contraindication is 

designed to prevent exposure and 

resultant adverse tissue reactions in 

allergic individuals. 

ii. Performance Test Recommendation 

The special controls guidance 

recommends a performance test to 

assess the biocompatibility of a dental 

amalgam device. Specifically, the 

guidance recommends that devices be 

tested in conformance with the 

following consensus standard: ‘‘ISO 

7405:1997(E), Dentistry—Preclinical 

evaluation of biocompatibility of 

medical devices used in dentistry—Test 

methods for dental materials.’’ 

Biocompatibility refers to the 

appropriate interaction between the 

device and the human body, and the 

minimization of risk of rejection or 

toxicity. Conformance to the 

recommended consensus standard will 

minimize the potential of a dental 

amalgam device to cause toxic or 

injurious effects by ensuring that the 

device will have the appropriate 

biological response for its intended use. 

c. Risk of Mercury Contamination 

When the mercury used to form 

dental amalgam is contaminated with 

impurities, such as oil, water, or other 

foreign matter, the amalgam may not 

harden properly. This may cause the 

device to be less effective. The special 

control to address this risk is a 

recommendation for a quality control 

test. 

The special controls guidance 

recommends a quality control test for 

the production of dental amalgam 

devices. Specifically, the guidance 

recommends that devices be tested in 

conformance with the ISO 

24234:2004(E) consensus standard. This 

standard includes quality control 

procedures for mercury, setting specific 

guidelines for visually inspecting 

mercury during production and 

observing its pouring characteristics. 

Among other things, this standard 

describes what visual signs indicate that 

a mercury sample is contaminated and 

therefore unsuitable for dental amalgam. 

The recommended quality control test 

will ensure that the mercury used in 

dental amalgam devices is free from 

contamination. 

d. Risk of Mechanical Failure 

If a dental amalgam device is not 

sufficiently strong, it will not be able to 

withstand the force of regular chewing. 

As a result, it may fracture and require 

replacement. The special controls to 

address the risk of mechanical failure 

are recommendations for (i) specific 

labeling and (ii) a performance test. 

i. Specific Labeling Recommendation 

The special controls guidance 

recommends the following specific 

labeling: 

■ Compressive strength (MPa) @ 24 

hrs. 

■ Dimensional change during 

hardening (%). 

■ Trituration time (s). 

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■ Working time (min). 

The recommended labeling will 

ensure that dental professionals are 

aware of the key physical properties of 

a dental amalgam device. This 

information will be useful in helping 

the professional decide if the device is 

suitable for an intended application. 

ii. Performance Test Recommendation 

The special controls guidance 

recommends that dental amalgam 

devices be tested in conformance with 

the ISO 24234:2004(E) performance 

standard. This standard calls for 

evaluation of the following physical 

properties: 

■ Complete chemical composition. 

■ Compressive strength (MPa) @ 1 hr. 

■ Compressive strength (MPa) @ 24 

hrs. 

■ Maximum creep (%). 

■ Dimensional change during 

hardening (%). 

■ Particle size distribution (μ) and 

shape, i.e., spherical, irregular, etc. 

■ Trituration time (s). 

■ Working time (min). 

The recommended performance test 

will evaluate key physical properties of 

dental amalgam devices that could 

affect their function. Analysis of these 

properties will enable FDA, through a 

premarket notification (510(k)) 

submission, to determine if a device has 

physical properties that are acceptable 

and are comparable to legally marketed 

devices. 

e. Risk of Corrosion 

Dental amalgam devices may corrode 

under certain conditions, including 

when they are placed in direct contact 

with other metals. If a dental amalgam 

device corrodes, it will lose its strength 

and will need to be replaced. Corrosion 

also increases the amount of mercury 

vapor a dental amalgam device releases. 

The special controls to address the risk 

of corrosion are recommendations for: 

(i) Specific labeling and (ii) a 

performance test for corrosion potential. 

i. Specific Labeling Recommendation 

The special controls guidance 

recommends the following specific 

labeling: 

■ Precaution: Do not place the device 

in direct contact with other types of 

metals. 

This labeling precaution 

recommendation will alert dental 

professionals of a potential material 

incompatibility between dental 

amalgam and other metal restoratives 

that may be present in the mouth, such 

as stainless steel, titanium, base metal 

alloys, and noble metal alloys. It will 

help ensure that a dental amalgam 

device is not placed in contact with a 

metal that will cause the device to 

corrode. 

ii. Performance Test Recommendation 

The special controls guidance 

recommends that dental amalgam 

devices be tested to assess their 

corrosion potential. Specifically, the 

guidance recommends that dental 

amalgam devices be tested in 

conformance with the ISO 

24234:2004(E) performance standard. 

This standard calls for an evaluation of 

corrosion byproducts, identifying the 

type and amount of substances leached 

from the device when corrosion occurs. 

The recommended performance test 

will provide information about what 

chemical products could be expected to 

be leached if the device were to corrode. 

This information will enable FDA, 

through a premarket notification 

(510(k)) submission, to determine if the 

device is acceptable and is comparable 

to legally marketed devices. 

f. Risk of Improper Use 

‘‘Improper use’’ of a device can result 

from misuse of the device. The special 

controls to address the risk of improper 

use are recommendations for specific 

labeling. 

The special controls guidance 

recommends the following specific 

labeling: 

■ Contraindication: Do not use in 

persons with a known mercury allergy. 

■ Precaution: Single-use only. 

The recommended labeling 

contraindiation will alert dental 

professionals of situations in which the 

use of a dental amalgam device is not 

recommended, such as in patients with 

a known mercury allergy. The 

recommended labeling precaution will 

inform dental professionals that a dental 

amalgam device is not intended to be 

reused. 

B. Statutory Authority 

FDA regulates devices, including 

dental devices, under the Federal Food, 

Drug, and Cosmetic Act (the act) (21 

U.S.C. 301 et seq.), and the act’s 

implementing regulations (parts 800 

through 898 (21 CFR parts 800 through 

898)). The Medical Device Amendments 

of 1976 (Pub. L. 94–295) amended the 

act to add premarket review authority 

and other authorities related to devices. 

Section 513 of the act (21 U.S.C. 360c) 

established three categories (classes) of 

devices, depending on the regulatory 

controls needed to provide reasonable 

assurance of their safety and 

effectiveness. The three categories of 

devices are class I devices, which are 

subject to general controls; class II 

devices, which are subject to general 

and ‘‘special’’ controls; and class III 

devices, for which premarket approval 

applications generally must be 

submitted. 

General controls include requirements 

for registration, listing, adverse event 

reporting, and good manufacturing 

practice (section 513(a)(1)(A) of the act). 

Special controls are controls that, in 

addition to general controls, are 

applicable to a class II device to help 

provide reasonable assurance of that 

device’s safety and effectiveness 

(section 513(a)(1)(B) of the act). Under 

the 1976 amendments, class II devices 

were defined as devices for which there 

was insufficient information to show 

that general controls themselves would 

provide reasonable assurance of safety 

and effectiveness, but for which there 

was sufficient information to establish 

performance standards to provide such 

assurance. The Safe Medical Devices 

Act of 1990 (SMDA) (Pub. L. 101–629) 

broadened the definition of class II 

devices to mean those devices for which 

the general controls by themselves are 

insufficient to provide reasonable 

assurance of safety and effectiveness, 

but for which there is sufficient 

information to establish special controls 

to provide such assurance, including 

performance standards, postmarket 

surveillance, patient registries, 

development and dissemination of 

guidelines, recommendations, and any 

other appropriate actions the agency 

deems necessary (section 513(a)(1)(B) of 

the act). The premarket approval 

requirements specify data and 

information that must be provided to 

FDA to obtain approval of a class III 

device (section 515 of the act (21 U.S.C. 

360e)). 

Devices that were in commercial 

distribution before the enactment of the 

Medical Device Amendments of 1976 

(May 28, 1976) are commonly referred 

to as ‘‘preamendments devices.’’ Under 

section 513 of the act, FDA classifies 

preamendments devices according to 

the following steps: (1) FDA receives a 

recommendation from a device 

classification panel (an FDA advisory 

committee); (2) FDA publishes the 

panel’s recommendation for comment, 

along with a proposed regulation 

classifying the device; and (3) FDA 

publishes a final regulation. FDA has 

classified most preamendments devices 

under these procedures. 

Section 513(e) of the act governs 

reclassification of preamendments 

devices. This section provides that FDA 

may reclassify a device by rulemaking 

based upon ‘‘new information.’’ FDA 

may initiate reclassification under 

section 513(e) or an interested person 

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38696 Federal Register / Vol. 74, No. 148 / Tuesday, August 4, 2009 / Rules and Regulations 

22 ‘‘Dental amalgam,’’ as it is referred to in this 

final rule, is a device that is a combination of two 

component devices, mercury and amalgam alloy. 

23Earlier prototypes were available from the 

1830s. 

24FDA is no longer using the term ‘‘dental 

mercury,’’ but instead is using ‘‘mercury,’’ to more 

accurately reflect the fact that the mercury used in 

dental amalgam is elemental mercury. 

25A panel of FDA’s Center for Devices and 

Radiological Health Medical Devices Advisory 

Committee. 

may petition FDA to reclassify a 

preamendments device. The term ‘‘new 

information,’’ as used in section 513(e) 

of the act, includes information 

developed as a result of a reevaluation 

of the data before the agency when the 

device was originally classified, as well 

as information not presented, not 

available, or not developed at that time. 

(See, e.g., Holland Rantos v. United 

States Department of Health, Education, 

and Welfare, 587 F.2d 1173, 1174 n.1 

(DC Cir. 1978); Upjohn v. Finch, 422 

F.2d 944 (6th Cir. 1970); Bell v. 

Goddard, 366 F.2d 177 (7th Cir. 1966)). 

Reevaluation of the data previously 

before the agency is an appropriate basis 

for subsequent regulatory action where 

the reevaluation is made in light of 

newly available regulatory authority 

(see Bell v. Goddard, supra, 366 F.2d at 

181; Ethicon, Inc. v. FDA, 762 F. Supp. 

382, 389–91 (D.D.C. 1991)), or in light 

of changes in ‘‘medical science.’’ (See 

Upjohn v. Finch, supra, 422 F.2d at 

951). Whether data before the agency are 

past or new data, the ‘‘new information’’ 

to support reclassification under section 

513(e) must be ‘‘valid scientific 

evidence,’’ as defined in section 

513(a)(3) of the act (21 U.S.C. 360c(a)(3)) 

and 21 CFR 860.7(c)(2). (See, e.g., 

General Medical Co. v. FDA, 770 F.2d 

214 (DC Cir. 1985); Contact Lens Assoc. 

v. FDA, 766 F.2d 592 (DC Cir.), cert. 

denied, 474 U.S. 1062 (1985)). 

FDA relies upon ‘‘valid scientific 

evidence’’ in the classification process 

to determine the level of regulation for 

devices (§ 860.7). For the purpose of 

reclassification, the valid scientific 

evidence upon which the agency relies 

must be publicly available. Publicly 

available information excludes trade 

secret and/or confidential commercial 

information, e.g., the contents of a 

pending premarket approval application 

(PMA). (See section 520(c) of the act (21 

U.S.C. 360j(c)). 

C. Regulatory History of the Devices 

1. Regulatory Status 

Dental amalgam 22 is a metallic 

restorative material that has been used 

for direct filling of carious lesions or 

structural defects in teeth since the 

1890s.23 It is a combination of two 

devices, mercury 24 (liquid) and 

amalgam alloy (powder), which is 

composed primarily of silver, tin, and 

copper. At the time FDA proposed to 

classify mercury and amalgam alloy, the 

devices were most commonly marketed 

individually in tablet/sachet or bulk 

form to be prepared by mixing the two 

devices in a dentist’s office, although 

the devices were also available in an 

already combined predosed, 

encapsulated form. Since the mid1980s, the device has been marketed 

most frequently in the predosed, 

encapsulated form. 

FDA classified mercury and amalgam 

alloy separately in accordance with the 

classification procedures for 

preamendments devices. In 1980, FDA 

published a proposed rule to classify 

amalgam alloy into class II, based on the 

recommendation of a device 

classification panel (Dec. 30, 1980, 45 

FR 85979), and finalized the 

classification of amalgam alloy into 

class II in the Federal Register of 

August 12, 1987 (52 FR 30099). 

Although FDA proposed classifying 

mercury into class II, in the Federal 

Register of August 12, 1987 (52 FR 

30089) FDA issued a final rule 

classifying mercury into class I. FDA 

explained that it believed that the 

general controls of the act, particularly 

the requirement that the device bear 

adequate directions for use, were 

sufficient to provide reasonable 

assurance of the safety and effectiveness 

of the device and to address the risk of 

rare allergic reactions among patients as 

well as the risk of toxicity among dental 

health professionals. 

FDA did not classify dental amalgam 

at the time it classified its two 

components, mercury and amalgam 

alloy. However, in accordance with its 

customary practice regarding regulation 

of devices composed of two or more 

devices, FDA has regulated the 

predosed, encapsulated form of dental 

amalgam in accordance with the 

requirements applicable to its 

component with the highest 

classification, i.e., amalgam alloy. 

Accordingly, dental amalgam devices 

entering the market have been regulated 

as class II devices under 21 CFR 

872.3050, amalgam alloy. 

2. Proposed Rule 

In the Federal Register of February 

20, 2002 (67 FR 7620), FDA published 

a proposed rule entitled ‘‘Dental 

Devices: Classification of Dental 

Amalgam and Reclassification of Dental 

Mercury; Issuance of Special Controls 

for Amalgam Alloy.’’ The proposed rule 

was based on the recommendation of 

the device advisory panel, information 

submitted in citizen petitions requesting 

the agency to take various actions with 

respect to the devices, a substantial 

amount of scientific data, and the 

results of several government safety 

assessments related to the devices (Refs. 

3, 4, 12). 

The Dental Products Panel 25 (the 

Panel) unanimously recommended that 

FDA classify dental amalgam in its 

encapsulated form into class II (Ref. 1). 

The Panel concluded that there are no 

major risks associated with 

encapsulated dental amalgam, when 

used as directed, but recognized there is 

a small population of patients who may 

experience allergic hypersensitive 

reactions to the materials in the device. 

The Panel also noted that improper use 

of the device exposes professionals to 

risks associated with mercury toxicity. 

To address these risks, the Panel 

recommended that the device be subject 

to voluntary performance standards, 

voluntary testing guidelines, and 

requirements that the device be used 

only on the written or oral authorization 

of a licensed practitioner, and only by 

persons with training or expertise in its 

use. 

The proposed rule included the 

following actions: (1) Classify 

encapsulated dental amalgam into class 

II (special controls); (2) amend the class 

II classification for amalgam alloy by 

designating special controls; and (3) 

reclassify mercury from class I (general 

controls) to class II (special controls). In 

the 2002 proposed rule, FDA identified 

risks to health associated with the use 

of dental amalgam, mercury, and 

amalgam alloy that it believed required 

the imposition of special controls that, 

in conjunction with the general controls 

of the act, would provide reasonable 

assurance of the safety and effectiveness 

of the device. The risks identified were 

mercury toxicity associated with the 

improper use of dental amalgam and 

allergic reactions in a small 

subpopulation of individuals. To 

mitigate these risks, FDA proposed a 

labeling guidance and compliance with 

recognized consensus standards as 

special controls for these devices. FDA 

proposed that all three devices be 

subject to the same special control 

guidance document, ‘‘Special Control 

Guidance Document on Encapsulated 

Amalgam, Amalgam Alloy, and Dental 

Mercury Labeling,’’ dated February 20, 

2002, as well as the following consensus 

standards, as relevant: (1) International 

Standards Organization (ISO) 1559:1995 

Dental Materials-Alloys for Dental 

Amalgam, and (2) American National 

Standards Institute/American Dental 

Association (ANSI/ADA) Specification 

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26Appendix A of the draft White Paper did list 

the inclusion and exclusion criteria for 

identification of relevant studies. 

27FDA decided to conduct this comprehensive 

review of the literature and prepare the Addendum 

rather than revise the White Paper. FDA finalized 

the White Paper with the addition of the 

Addendum. 

No. 6–1987 for Dental Mercury. The 

comment period on the proposed rule 

was reopened on July 17, 2002 (67 FR 

46941), and again on April 28, 2008 (73 

FR 22877), to permit additional 

opportunities for public comment 

(Docket No. FDA–2008–N–0163). 

3. Scientific Information, Safety 

Assessments, and Adverse Event 

Reports Regarding Dental Amalgam 

a. Information and Assessments 

Discussed in the Proposed Rule 

Before issuing the proposed rule, FDA 

carefully examined extensive 

information related to the safety and 

effectiveness of dental amalgam. This 

information included a comprehensive 

safety assessment of dental amalgam 

performed by the U.S. Public Health 

Service (PHS), U.S. government research 

related to dental amalgam, studies and 

other information submitted in citizen 

petitions to the agency, several national 

and international comprehensive 

reviews of scientific information about 

the risks and benefits of the device, 

comprehensive safety assessments of 

dental products that contain mercury by 

international health organizations and 

foreign countries, and the scientific 

literature reviewed by the Panel. See 67 

FR 7621–7625 (Feb. 20, 2002). 

b. Information and Assessments That 

Have Become Available Since 

Publication of the Proposed Rule 

i. Life Sciences Research Office (LSRO) 

Report 

In 2004, the Trans-agency Working 

Group on the Health Effects of Dental 

Amalgam completed a comprehensive 

review of approximately 300 peerreviewed studies of dental amalgam and 

mercury vapor published from 1996 

through 2003 (LSRO report) (Ref. 13). 

The project was completed under 

contract by Life Sciences Research 

Office, Inc. (LSRO), and was funded by 

the National Institutes of Health (NIH), 

in cooperation with FDA, the Centers 

for Disease Control and Prevention 

(CDC), and the Office of the Chief Dental 

Officer of the Public Health Service. In 

conducting the review, LSRO engaged 

an independent panel of experts from 

academia in the fields of 

immunotoxicology, immunology, and 

allergy; neurobehavioral toxicology and 

neurodevelopment; pediatrics; 

developmental and reproductive 

toxicology; toxicokinetics and modeling; 

occupational health and epidemiology; 

pathology; and general toxicology. The 

LSRO report concluded that there is 

little evidence to support claims of a 

causal relationship between mercury 

fillings and human health problems, 

such as kidney or cognitive dysfunction; 

neurodegenerative disease, specifically 

Alzheimer’s disease or Parkinson’s 

disease; or autoimmune disease (Refs. 

13, 67). The report also identified 

important data gaps, including whether 

low-level mercury vapor results in 

neurotoxicity, whether low-level in 

utero exposure to mercury vapor affects 

the developing brain, and whether 

occupational exposure to mercury vapor 

affects reproductive and/or pregnancy 

outcomes. 

ii. White Paper and Addendum 

Scientific Reviews 

In an effort to assess whether peerreviewed literature published since 

FDA’s 1997 safety assessment of dental 

amalgam (Ref. 12) presented new 

information on the potential health risks 

of dental amalgam, FDA’s National 

Center for Toxicological Research 

(NCTR) prepared a White Paper review 

(Ref. 10). Rather than duplicate previous 

extensive reviews of the scientific 

literature by U.S. government agencies 

and international organizations, NCTR 

chose to build on the previous reviews 

and conducted an in-depth evaluation 

of 34 primary research articles that were 

chosen for their scientific merit, 

relevance, and potential to provide the 

most significant current information 

regarding the potential health risks 

associated with exposure to mercury in 

dental amalgam. The conclusion in the 

draft White Paper was that the peerreviewed scientific information 

published since 1997 was consistent 

with FDA’s previous assessment that, 

except for persons with rare allergic or 

hypersensitivity reactions, individuals 

with dental amalgam restorations do not 

experience adverse effects from the 

device. 

On September 6 and 7, 2006, FDA 

presented the findings of the White 

Paper in draft to a joint meeting of the 

Dental Products Panel and the 

Peripheral and Central Nervous System 

Drugs Advisory Committee (the 2006 

Panel). At that time, FDA also opened 

a docket related to the meeting to 

facilitate public submission of 

information regarding the potential 

health risks of mercury in dental 

amalgam (Docket No. FDA–2006–N– 

0543 (formerly 2006N–0352)). 

The 2006 Panel heard from numerous 

public speakers, and then deliberated 

and made recommendations on a series 

of questions FDA had posed on its draft 

White Paper (Ref. 66). The committee 

concluded that FDA’s draft White Paper 

had significant limitations, such as the 

fact that the literature search used a 

single database (PubMed), the Paper did 

not satisfactorily explain how the 

scientific references were chosen,26 and 

it failed to identify significant gaps in 

the scientific knowledge, particularly 

with respect to exposure limits and 

possible health risks for sensitive 

subpopulations. The majority of the 

2006 Panel voted that it could not find 

the conclusions of the draft White Paper 

to be ‘‘reasonable’’ in light of these 

limitations. In their closing comments, 

the panelists provided individual 

recommendations, including the 

individual (not consensus) 

recommendations that FDA consider 

labeling requirements related to the use 

of dental amalgam in pregnant women 

and small children, that manufacturers 

be required to provide information to 

patients to ensure that they understand 

that the devices contain mercury, and 

that the Federal government (public 

health agencies) research the effects of 

dental amalgam mercury on 

reproductive health and developing 

fetuses. 

In response to the deliberations and 

recommendations of the 2006 Panel, 

FDA conducted a more comprehensive 

review of the scientific literature in an 

Addendum to the White Paper (Ref. 11). 

In total, more than 200 scientific 

articles, including 33 case studies, were 

considered in the White Paper and its 

Addendum.27

The conclusions of the Addendum 

generally confirmed the conclusions of 

the White Paper and previous 

assessments by other organizations and 

agencies regarding the potential health 

risks presented by the presence of 

mercury in dental amalgam. More 

specifically, the articles and case studies 

reviewed in the Addendum to the White 

Paper were consistent with the 

conclusion in earlier government safety 

assessments (Refs. 3, 4, 12) that 

exposures to mercury vapor from dental 

amalgam are not associated with 

adverse health effects in the population 

age six and older (see also section I.A.). 

As discussed in the Addendum, FDA 

also concluded that prospective clinical 

studies of dental amalgam published to 

date (Refs. 31, 32, 34, 40, 46, 47, 68) 

found no neurological deficits in 

children who first received dental 

amalgam restorations at ages six to ten 

and were followed for five or seven 

years. FDA concluded, however, that 

the clinical data are limited regarding 

certain subpopulations (pregnant 

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28The death report appears to have been 

misclassified because it was self reported (an actual 

death had not occurred). This report attributes 

symptoms of joint pain, neurological spasms, a 

compromised immune system, and a variety of 

other physical symptoms to dental amalgam. 

29FDA estimates that dental amalgam has been 

used in approximately one billion restorations 

between 1988 and 2008. 

women and their developing fetuses, 

and children under the age of six, 

including breastfed infants). 

c. Adverse Event Reports 

As part of FDA’s effort to determine 

the appropriate regulatory controls to 

provide reasonable assurance of the 

safety and effectiveness of dental 

amalgam, FDA reviewed all adverse 

event reports submitted to MedWatch 

for dental amalgam devices through 

2008. The review identified 141 reports, 

dating back to 1988, including 102 

reports of injuries, 12 reports of 

malfunctions, 26 miscellaneous 

complaints, and 1 misreported death.28

The large majority of the injury reports 

were submitted voluntarily by 

individual patients. The malfunction 

reports were submitted primarily by 

health professionals and two reports 

were submitted by manufacturers. 

The malfunction reports described 

problems with encapsulated amalgam 

such as product shrinkage, inaccurate 

powder to liquid ratios, and capsule 

leaking. There were also some reports of 

mercury spills as a result of mixing 

(triturating) amalgam capsules. 

The injury reports described a wide 

array of conditions and symptoms that 

individual patients believed to be 

caused by their dental amalgam fillings. 

The conditions and symptoms reported 

included fatigue, headaches, joint pain, 

brain ‘‘fog,’’ depression, neuropathy, 

rheumatoid arthritis, hypothyroidism, 

visual impairments, hearing loss, 

allergies, kidney damage, attention 

deficit disorder, irritable bowel 

syndrome, seizures, abnormal menstrual 

cycle, weight loss, and developmental 

problems, such as autism, attention 

deficit hyperactivity disorder, and 

unidentified congenital defects. Several 

reporters stated that they experienced 

relief from their symptoms when their 

amalgam fillings were removed, while 

others stated that their symptoms did 

not appear until after their fillings were 

removed. 

The great majority of the adverse 

event reports submitted to FDA 

regarding dental amalgam are anecdotal 

and lack specific details, such as when 

symptoms first appeared, how they 

progressed, and what may have caused 

onset or relief of certain symptoms. In 

addition, the reports frequently were not 

made until years after the events 

occurred. Because of these factors, FDA 

is unable to assess the relationship of 

the reported adverse effects with the 

device. FDA notes, however, that the 

number of adverse event reports it has 

received regarding dental amalgam is 

quite low in light of the device’s long 

history of use in tens of millions of 

dental restorations in the United States 

each year.29

II. Development of the Final Rule 

In developing this final rule, FDA 

considered the comments and 

information submitted in response to 

the proposed rule, the scientific 

reviews, studies, and safety assessments 

described above, and its analysis of the 

adverse event reports submitted. The 

final rule and the special controls 

guidance document are consistent with 

the proposed regulation, although they 

reflect several changes made in response 

to the comments and information 

received. As proposed, the final rule 

classifies dental amalgam into class II, 

reclassifies mercury from class I to class 

II, and designates a special control for 

dental amalgam, mercury, and amalgam 

alloy. However, the final rule classifies 

the three devices together in a single 

regulation and uses the term ‘‘mercury’’ 

instead of ‘‘dental mercury.’’ 

The special controls guidance 

document specifically revises the draft 

special controls guidance document as 

follows: 

• Includes recommendations related 

to the updated relevant consensus 

standards, rather than designating these 

standards as separate special controls. 

• Includes recommendations 

regarding device composition, 

performance data, warnings, and 

labeling precautions. 

• Recommends a contraindication 

against use in persons with a known 

mercury allergy. 

• Recommends that the labeling 

include an information for use (IFU) 

statement. 

• Updates recommendations 

regarding performance testing to be 

included in 510(k) submissions to 

include strength, creep, dimensional 

change, particle shape and distribution, 

corrosion products, and amount of 

mercury vapor released. 

• Replaces the recommendation that 

each ingredient of the device be listed 

in the labeling with the 

recommendation that the primary 

ingredients be listed, and that the 

labeling state that the device contains 

mercury. 

• Replaces the recommendation that 

the labeling warn that the device 

contains zinc with the recommendation 

that the labeling warn that the device 

contains mercury. FDA believes that the 

effects of zinc on the expansion of 

dental amalgam are well understood 

and that a warning that the device 

contains zinc is not necessary to provide 

a reasonable assurance of the safety and 

effectiveness of the device. In contrast, 

as discussed in section I.A., FDA 

recommends that the device bear a 

warning that the device contains 

mercury because FDA believes such a 

warning is necessary to provide a 

reasonable assurance of safety and 

effectiveness because of the potential 

risks to health of exposure to mercury 

and toxicity and adverse tissue reaction. 

• Deletes recommendations regarding 

packaging and handling because FDA 

has concluded that these 

recommendations are not necessary to 

provide a reasonable assurance of the 

safety and effectiveness of the device. 

In this final rule, FDA is designating 

a special controls guidance document 

(described in section I.A.) that, along 

with the general controls under the act, 

will provide reasonable assurance of the 

safety and effectiveness of the device. 

Elsewhere in this issue of the Federal 

Register, FDA is announcing the 

availability of the special controls 

guidance. Following the effective date of 

this final rule, any firm submitting a 

510(k) premarket notification for dental 

amalgam, as well as any firm currently 

marketing the device, must address the 

risks to health identified in the special 

controls guidance document. Firms 

marketing or intending to market 

mercury or amalgam alloy must address 

the risks to health identified in the 

special controls guidance document that 

apply to those devices. 

When a guidance document is 

established as a special control by 

rulemaking, manufacturers are required 

to address the issues identified in the 

guidance, either by following the 

recommendations in the guidance or by 

some other means that provides 

equivalent assurances of safety and 

effectiveness. If a manufacturer 

proposes to use a means other than the 

recommendations set forth in the 

special controls guidance, it is required 

to demonstrate that the alternative 

means provides equivalent assurances 

of safety and effectiveness. 

III. Comments and FDA’s Responses 

As stated previously, in addition to 

the comment period provided when the 

proposed rule was issued in 2002, FDA 

reopened the comment period on the 

rule in July 2002 and again in April 

2008. Altogether, FDA received more 

than 1,400 comments on the proposed 

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30FDA also received more than 1,800 comments 

to the docket for the 2006 Panel meeting on dental 

amalgam (Docket No. 2006N–0352), which had 

been established to permit persons to comment and 

provide information on the issues and questions 

raised at the meeting. FDA reviewed and 

considered those comments in finalizing this 

regulation. 

31There is no question regarding the effectiveness 

of the device. It is undisputed that the device has 

been used effectively in millions of dental 

restorations over 100 years. 

rule and the draft special controls 

guidance document. The commenters 

included consumers, health 

professionals, industry, academia, State 

and Federal agencies, professional 

societies, and organizations. Because of 

the intertwined nature of the documents 

and the significant duplication of 

comments, FDA is summarizing and 

responding to the comments it received 

on both the proposed rule and the draft 

special controls guidance document in 

this preamble.30

In the 2008 Federal Register notice 

reopening the comment period on the 

proposed rule, FDA requested 

comments supported by empirical data 

and scientific evidence on specific 

topics relating to the classification of the 

devices and the special controls that 

should apply to them if they were 

classified into class II. FDA requested 

comments on whether the proposed 

special controls (materials and labeling) 

would provide reasonable assurance of 

the safety and effectiveness of the 

devices if they were placed in class II, 

and on whether the proposed special 

controls guidance document should be 

revised in light of the recommendations 

and discussions of the 2006 Panel. FDA 

also sought information related to the 

agency’s analysis of the benefits and 

costs of the various regulatory options 

for classifying the devices, including the 

number of annual procedures in which 

the devices are used, trends in the use 

of various restorative devices, 

information regarding alternatives to 

dental amalgam, how labeling 

describing the risks in certain 

populations might affect demand, how 

such risks should be communicated, 

information regarding the current level 

of mercury to which patients and 

professionals are exposed, and whether 

that exposure might be reduced by using 

alternatives to dental amalgam. 

A. Classification 

(Comment) FDA received many 

comments regarding the appropriate 

classification of these devices. The 

comments generally did not distinguish 

among dental amalgam, mercury, and 

amalgam alloy, treating them as one 

device, dental amalgam. Many 

comments urged the agency to classify 

the device into class III (premarket 

approval), frequently stating safety 

concerns. For example, some 

commentators urged the agency to 

classify dental amalgam into class III 

because, as a class III device, ‘‘[it would 

be] presumed as unsafe and needing to 

be proven safe before general use can be 

allowed’’ and that ‘‘it should be placed 

in class III where manufacturers are 

forced to prove that it is safe, not the 

class II where it can continue to be 

grandfathered.’’ Others believed the 

device should be classified into class II 

because there is sufficient information 

to establish special controls for the 

device that would provide reasonable 

assurance of its safety and effectiveness. 

One comment stated that special 

controls were unnecessary because it 

believed that the general controls of the 

act are sufficient to provide reasonable 

assurance of the safety and effectiveness 

of the device. 

(Response) FDA has determined that 

class II with a designated special 

controls guidance document will 

provide a reasonable assurance of safety 

and effectiveness for dental amalgam. In 

reaching this determination, FDA made 

the findings required by § 860.7(d)(1) 

that, first, when subject to the general 

controls of the act and the designated 

special control, and when accompanied 

by warnings against unsafe use in 

individuals who are allergic to mercury, 

the probable benefits to health from use 

of the device outweigh any probable 

risks. Second, FDA has determined that, 

when subject to the general controls of 

the act and the designated special 

control, valid scientific evidence 

demonstrates the absence of 

unreasonable risk of illness or injury 

associated with the use of the device for 

its intended uses and conditions of use. 

FDA classifies devices in accordance 

with the statutory criteria in section 513 

of the act. As provided in section 513, 

class I devices are devices for which the 

general controls of the act are sufficient 

to provide reasonable assurance of 

safety and effectiveness. Class II devices 

are devices for which general controls 

are not sufficient to provide reasonable 

assurance of safety and effectiveness, 

but for which there is sufficient 

information to establish special controls 

that, along with the general controls of 

the act, will provide such assurance. 

Class III devices are devices for which 

premarket approval is necessary to 

provide reasonable assurance of safety 

and effectiveness. 

As stated above, FDA relies on valid 

scientific evidence in making 

determinations regarding classification. 

Valid scientific evidence is defined as 

‘‘evidence from well-controlled 

investigations, partially controlled 

studies, studies and objective trials 

without matched controls, welldocumented case histories conducted by 

qualified experts, and reports of 

significant human experience with a 

marketed device, from which it can 

fairly and responsibly be concluded by 

qualified experts that there is reasonable 

assurance of the safety and effectiveness 

of a device under its conditions of use.’’ 

§ 860.7(c)(2). Consistent with the 

regulation, FDA does not rely on 

isolated case reports, random 

experience, reports lacking sufficient 

details to permit scientific evaluation, or 

unsubstantiated opinions. The valid 

scientific evidence to support 

classification of a device may vary 

according to, among other things, the 

existence and adequacy of warnings and 

restrictions, and the extent of 

experience with use of the device. 

§ 860.7(c)(2). 

The standard for determining whether 

there is reasonable assurance that a 

device is safe is described in 

§ 860.7(d)(1).31 According to that 

section, ‘‘[t]here is reasonable assurance 

that a device is safe when it can be 

determined, based on valid scientific 

evidence, that the probable benefits to 

health from use of the device for its 

intended uses and conditions of use, 

when accompanied by adequate 

directions and warnings against unsafe 

use, outweigh any probable risks. The 

valid scientific evidence used to 

determine the safety of a device shall 

adequately demonstrate the absence of 

unreasonable risk of illness or injury 

associated with the use of the device for 

its intended uses and conditions of 

use.’’ 

In determining the appropriate 

classification of dental amalgam, FDA 

has relied on valid scientific evidence, 

including, as described in detail in 

section I.A., several comprehensive 

reviews of the scientific literature and 

safety assessments, air monitoring 

standards for mercury vapor, biological 

monitoring standards for urine mercury, 

and clinical studies. Based on its review 

of this information, FDA concludes that 

exposures to mercury vapor from dental 

amalgam are not associated with 

adverse health effects in the population 

age six and older. With respect to 

potentially sensitive populations, i.e., 

fetuses, breastfed infants, and children 

under six years of age, FDA would not 

expect to see any adverse health effects 

in these subpopulations from mercury 

vapors released from dental amalgam, 

although clinical data are limited. These 

conclusions are supported by 

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32The classification panel identified a dental 

implant as ‘‘a device that is surgically placed into, 

or in opposition to, the maxilla or mandible and 

which protrudes through the mucosa of the oral 

cavity’’ (45 FR 85964). Dental restorative materials 

such as amalgam do not protrude through the 

mucosa of the oral cavity and, therefore, are not 

considered implants. 

independent investigations by other 

scientific bodies, such as the European 

Commission’s Scientific Committee on 

Emerging and Newly Identified Health 

Risks (SCENIHR), which stated in 2007 

(Ref. 6) that ‘‘no risks of adverse 

systemic effects exist and the current 

use of dental amalgam does not pose a 

risk of systemic disease.’’ 

Consistent with the regulation 

defining valid scientific evidence, in 

determining the appropriate 

classification of dental amalgam, FDA 

has considered the device’s long history 

of use in tens of millions of procedures 

in the United States each year, as well 

as the information available regarding 

that use. FDA has also considered the 

adequacy of warnings and the fact that 

the device is a prescription device and, 

therefore, available to patients only with 

the involvement of a health care 

provider. Finally, FDA has considered 

the probable benefits to health from use 

of the device, such as its strength, 

marginal integrity, suitability for large 

occlusal surfaces, durability, ease of 

placement, and low failure and 

complication rates. 

FDA recognizes that dental amalgam 

releases low levels of mercury, and that 

there are scientific data showing 

mercury vapor, at high enough 

exposures, to be a neurotoxicant and 

nephrotoxicant. FDA also recognizes 

that certain individuals are allergic to 

mercury. In addition, there is very 

limited to no clinical information 

available regarding long-term health 

outcomes in pregnant women and their 

developing fetuses, and children under 

the age of six, including infants who are 

breastfed. FDA believes that, in order to 

provide reasonable assurance of the 

safety of dental amalgam, it is important 

that dentists are informed that the 

device contains mercury, that it is 

contraindicated against use in persons 

with a known allergy to mercury, and 

that the labeling include an information 

for use statement discussing the 

benefits, risks, and scientific study 

information. 

FDA has concluded that general 

controls alone are not sufficient to 

address the identified risks to health 

presented by dental amalgam and thus 

provide reasonable assurance of its 

safety and effectiveness. FDA has also 

determined that premarket approval is 

not necessary to provide such assurance 

because there is sufficient information 

to establish special controls that, in 

conjunction with the general controls 

under the act, will provide reasonable 

assurance of the safety and effectiveness 

of the device. Specifically, FDA has 

concluded that the recommendations in 

the special controls guidance document, 

including the recommended labeling 

statements, along with the general 

controls of the act, are sufficient to 

provide a reasonable assurance of the 

safety and effectiveness of the device. 

In accordance with § 860.7(d)(1), FDA 

has also concluded that, when subject to 

the general controls of the act and the 

designated special control, and when 

accompanied by warnings against 

unsafe use in individuals who are 

allergic to mercury, the probable 

benefits to health from use of the device 

outweigh any probable risks. Finally, 

FDA has determined that, when subject 

to the general controls of the act and the 

designated special control, valid 

scientific evidence demonstrates the 

absence of unreasonable risk of illness 

or injury associated with the use of the 

device for its intended uses and 

conditions of use. 

(Comment) Some comments were 

opposed to ‘‘FDA reclassifying mercuryencapsulated amalgam dental fillings as 

a class II,’’ stating that ‘‘FDA is moving 

quickly to approve mercury.’’ 

(Response) These comments reflect a 

misunderstanding of the device 

classification process. Mercury, 

amalgam alloy, and dental amalgam are 

legally marketed preamendments 

devices. As explained above, 

preamendments devices are subject to 

specific classification procedures. In 

1987, FDA classified mercury and 

amalgam alloy through notice and 

comment rulemaking, as required by the 

statute. Although FDA did not classify 

dental amalgam (the combination of 

those two devices) at that time, the 

device has been regulated in accordance 

with the requirements applicable to its 

component with the highest 

classification, i.e., amalgam alloy. In 

2002, the agency issued a proposed rule 

to classify dental amalgam. Consistent 

with that proposed rule, FDA is now 

classifying the device into class II 

subject to a special control that, along 

with the general controls under the act, 

will provide reasonable assurance of its 

safety and effectiveness. Thus, this rule 

does not constitute an ‘‘approval’’ for 

marketing, but rather establishes 

additional regulatory controls for the 

device. 

(Comment) One comment stated that 

dental amalgam should be regulated as 

a class III device because it is an 

implant. 

(Response) FDA disagrees with the 

comment. As explained in the Federal 

Register of December 30, 1980 (45 FR 

85962 at 85964), FDA does not consider 

restorative materials placed in the teeth, 

such as dental amalgam, to be 

implants.32 Moreover, even if the 

devices were considered to be implants, 

FDA would not be required to classify 

them into class III. In accordance with 

section 513(d)(2)(B) of the act (21 U.S.C. 

360c(d)(2)(B)) and 21 CFR 860.93, an 

implant may be classified into class I or 

class II if FDA determines that 

premarket approval is not necessary to 

provide reasonable assurance of its 

safety and effectiveness. As stated 

above, FDA has made this 

determination with respect to dental 

amalgam. 

B. Banning 

(Comment) Some comments stated 

that dental amalgam should be banned 

because it is poisonous and not safe for 

use in dentistry. Other comments 

requested that dental amalgam be 

banned for children 18 and under, 

women of childbearing age, pregnant 

women, nursing mothers, and persons 

with compromised immune systems and 

kidney problems. Some comments 

suggested that FDA employ the 

‘‘precautionary principle’’ adopted by 

other countries to protect these 

populations. In contrast, other 

comments noted that no scientific study 

or assessment has found a causal link 

between dental amalgam and adverse 

health effects in either the general 

population or in any sensitive 

subpopulation, and that the device has 

been used safely for many years in 

millions of dental restorations. 

(Response) As discussed in detail 

above, FDA disagrees that the levels of 

mercury released from dental amalgam 

contribute to adverse health outcomes 

or is unsafe for use in dentistry when 

used with appropriate occupational 

health controls for dental offices. FDA 

recognizes that certain countries, e.g., 

Norway, Sweden, and Denmark, have 

banned dental amalgam, adopting a 

‘‘precautionary principle’’ approach 

(taking preventive action despite 

uncertainty regarding the need for such 

action). However, FDA regulates 

devices, like dental amalgam, in 

accordance with the requirements of the 

act. As explained above, in accordance 

with the statutory criteria for classifying 

devices, FDA has concluded that there 

is sufficient information from which to 

establish special controls that, along 

with the general controls of the act, will 

provide reasonable assurance of the 

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safety and effectiveness of the device. 

Specifically, FDA has determined that 

the risks to health presented by dental 

amalgam can be addressed through the 

general controls of the act in 

conjunction with the recommendations 

in the special controls guidance 

document. Because of this 

determination, FDA disagrees with 

comments suggesting that the device 

should be banned. 

C. Mercury Content and Toxicity 

(Comment) One comment stated that 

the labeling of the device should 

disclose the fact that it contains 

mercury, citing to a recent poll showing 

that 76 percent of Americans do not 

know that the primary component of 

amalgam fillings is mercury. Another 

comment stated that the amount of 

mercury vapor released from dental 

amalgam also should be disclosed. 

(Response) FDA agrees that the 

labeling of the device should disclose 

the fact that it contains mercury. 

Accordingly, the special controls 

guidance recommends that the labeling 

include a warning that the device 

contains mercury and disclose the total 

mercury content (% by mass). FDA has 

concluded that labeling disclosing the 

amount of mercury vapor released from 

the device would not provide useful 

information because the mercury vapor 

released in a clinical setting varies 

among patients and is dependent on 

several variables, such as age and wear 

of the restoration, as well as the diet and 

chewing habits of the patient. FDA 

believes, however, the recommended 

warning about the presence of mercury 

in a dental amalgam device and the 

recommended disclosure of mercury 

content by weight will alert dental 

professionals of the potential for 

exposure to mercury vapor and will 

remind them of the need for protective 

measures, such as the use of gloves 

when handling the device. The 

recommended precaution about the 

need for adequate ventilation will 

encourage professionals to use a 

vacuum pump and adequate ventilation 

during placement of dental amalgams to 

minimize the amount of mercury vapor 

that they or their patients may inhale. 

Moreover, FDA is recommending that, 

to establish substantial equivalence to a 

legally marketed device in a 510(k) 

premarket notification, manufacturers 

conduct a test showing that the amount 

of mercury vapor released due to 

corrosion is acceptable when evaluated 

using an FDA-recognized standard or an 

equivalent method of evaluating the 

amount of mercury vapor released due 

to corrosion. 

(Comment) Several comments were 

submitted in response to FDA’s request 

for information on the current level of 

exposure to the mercury in dental 

amalgam for patients and dental 

professionals. One comment stated that 

dental amalgams release 0.53 

micrograms of mercury per surface per 

day, resulting in an uptake into the 

blood stream of 0.081 micrograms of 

mercury per surface per day, well below 

the World Health Organization (WHO) 

Acceptable Daily Intake (ADI) levels of 

40 micrograms/day or 300 micrograms/ 

day for demonstrable health effects to 

the most sensitive individual. Another 

comment stated that dental amalgam 

fillings release 4 to 22 micrograms/cm2

per day, that those amounts are 

increased further by galvanism, heat, or 

chewing, and that data show an average 

of 60 micrograms of mercury are 

excreted daily in the feces of the average 

patient with amalgam fillings. Another 

comment stated that the average urinary 

mercury concentrations in children (age 

six and older) with amalgam fillings 

range from 0.1 to 5.7 micrograms/gram 

creatinine, as compared to 0.1 to 2.9 

micrograms/gram creatinine for children 

with composite fillings. Another 

comment stated that health screenings 

of dental professionals from 1997–2007 

found an average urinary mercury 

concentration of approximately 2.5 

micrograms/L and that this level is 

within the range of the urinary mercury 

concentration found in individuals who 

are not exposed to mercury in their 

occupations. Finally, one comment 

stated that there are 0.2 micrograms of 

mercury in the breathing zone of 

dentists during placement and removal 

of amalgam. 

(Response) FDA agrees with the 

comments that the current level of 

exposure to mercury in dental amalgam, 

for patients with restorations and dental 

professionals exposed occupationally, is 

below the accepted threshold levels for 

the most subtle health effects and is 

consistent with the conclusions of 

previous safety assessments (Refs. 3, 6, 

12, 13) that the mercury in dental 

amalgam does not present a risk to 

health for the population age six and 

older. While the fact that dental 

amalgam releases mercury vapor has 

been known for a long time, it is 

difficult to make accurate estimates of 

the amount of mercury released from 

amalgam and subsequent absorption of 

mercury in the body using an air 

monitoring approach. These difficulties 

account for the disparate range of values 

reported in the literature, some of which 

are noted in the comment above. 

Because of the difficulties noted in 

determining a robust estimate of daily 

dose of mercury resulting from 

monitoring of mercury vapor in the oral 

cavity, as discussed in section I.A., FDA 

is primarily relying on a consensus 

estimate of 1–5 μg/day for adults (Refs. 

3, 22). 

FDA also recognizes that good dental 

hygiene practices, such as the use of 

vacuum pumps and chair-side traps, 

have greatly reduced the level of 

mercury to which dental professionals 

are exposed. Nevertheless, because 

dental amalgam releases mercury vapor 

and is associated with a risk of human 

exposure to this vapor, and because 

some individuals have a known allergy 

to mercury, FDA is recommending that 

the labeling warn that the device 

contains mercury, contain a precaution 

that it should be used with proper 

ventilation, and include a 

contraindication against use in persons 

with a known allergy to mercury. 

(Comment) A few comments stated 

that dental amalgam fillings contribute 

to the majority of the mercury body 

burden in the general population and 

that urinary mercury concentrations are 

not measures of mercury body burden, 

but rather represent a combination of 

the amount of mercury to which an 

individual has been exposed and his or 

her ability to excrete mercury. The 

comments added that 90 percent of 

mercury is excreted from the body 

through the fecal route, and that low 

urinary mercury concentrations are not 

an accurate predictor of mercury 

exposure. Some comments stated that 

data obtained from autopsies 

demonstrate that high mercury levels 

are present in the brain and kidneys, 

despite dental amalgam mercury 

exposure levels being below safety 

limits. A few comments noted that 

mercury passes through both the 

umbilical cord and the blood/brain 

barrier. 

(Response) FDA recognizes that 

dental amalgam contributes to the 

majority of the body burden of mercury 

for many people not occupationally 

exposed to mercury (Ref. 22). FDA 

recognizes that urine and feces are 

major routes of mercury excretion, but 

also recognizes that which excretion 

route predominates is dependent on the 

mercury species. The ‘‘90% mercury 

excreted by the fecal route’’ relates to 

excretion of organic methylmercury, 

and this high percent is not the case for 

inorganic forms of mercury, where the 

urinary route predominates, especially 

in the case of chronic mercury vapor 

exposure (Refs. 14, 69, 70). The amount 

of mercury excreted into feces is not a 

well-accepted index of exposure to 

elemental mercury vapor. Further, the 

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correlation of fecal mercury levels, 

mercury vapor exposure, and adverse 

health effects has not been reliably 

established, as has been shown for 

urinary mercury concentrations. Fecal 

mercury concentrations might increase 

during removal of dental amalgams due 

to swallowing amalgam particles. Fecal 

levels might also be elevated from 

dietary exposure to methylmercury, 

which undergoes extensive 

enterohepatic recycling between the GI 

tract and liver biliary excretion system. 

FDA disagrees with the comment that 

urinary mercury concentrations are not 

accurate measures of inorganic mercury, 

including mercury vapor, exposure. In 

fact, FDA and other public health 

agencies, such as ATSDR (Ref. 14), and 

WHO (Refs. 21, 22), consider urinary 

mercury concentrations to be the most 

accurate and widely used biomarker for 

assessing the absorbed dose that results 

from chronic mercury vapor exposure. 

For example, in a number of 

occupational studies, strong correlations 

have been found between daily, timeweighted air concentrations (which are 

considerably higher than exposures to 

dental amalgam mercury) and urinary 

mercury concentrations in workers 

(Refs. 14, 21). In studies evaluating 

dental amalgam mercury exposure, 

urinary mercury concentrations have 

been shown to be proportional to the 

number of amalgam restorations and/or 

surfaces in the mouth. 

FDA is aware that, in autopsy studies, 

mercury has been found to accumulate 

in the brain. However, it is difficult to 

draw conclusions from autopsy studies 

regarding a potential association 

between exposure to dental amalgam 

and adverse health outcomes without 

information concerning the individual’s 

lifetime history of exposure to mercury 

from fish and other environmental 

sources. Similarly, even in cases 

attempting to find an association, 

meaningful conclusions could not be 

drawn between neurodegenerative 

disorders, the number of dental 

amalgams, and the amount of 

accumulated mercury, because it is 

possible that damaged neuronal cells in 

patients with neurodegenerative 

disorders are able to accumulate more 

mercury than healthy cells (Ref. 70). 

In response to the comments noting 

that mercury passes through both the 

umbilical cord, FDA agrees that mercury 

vapor has the ability to cross the 

placental barrier. As discussed in detail 

in section I.A., FDA found that the 

limited human data do not demonstrate 

an association between exposure to the 

mercury in dental amalgam and adverse 

reproductive outcomes such as low 

birth weight babies or increased rates of 

miscarriage. Moreover, FDA also 

reviewed several well-conducted 

studies designed to assess high-level 

mercury vapor exposure on 

developmental effects in pregnant 

animals and their offspring. In one 

study no effects were observed on 

peripheral, somatosensory, auditory, or 

visual neurological functions in 

offspring of rats exposed to mercury 

vapor prenatally (Ref. 48). In another 

study, prenatal exposure of pregnant 

rats was associated with adverse effects 

on fetal development only in cases 

where maternal exposure to mercury 

vapor was so high that it became toxic 

to the mother (leading to decreased 

maternal body weight) (Ref. 44). More 

details are provided in section I.A. 

(Comment) One comment stated that 

mercury in dental amalgam is more 

toxic than mercury in fish. 

(Response) The form of mercury in 

dental amalgam (mercury vapor) is 

different from the form of mercury in 

fish (methylmercury). These two types 

of mercury differ in terms of kinetic 

behavior, mechanism of action, 

exposure routes, and tissue targets. For 

the purpose of classifying dental 

amalgam, FDA is addressing only the 

form of mercury in that device. As 

discussed in detail above, FDA 

disagrees that the levels of mercury 

released from dental amalgam are 

unsafe. 

(Comment) A few comments stated 

that toxic/allergic reactions to mercury 

in dental amalgam may produce 

autoimmune conditions such as lichen 

planus lesions, eczema, pustulosis, and 

dermatitis, and often play a role in the 

pathogenesis of periodontal disease. 

(Response) After reviewing 23 case 

studies and several epidemiological 

studies in the Addendum to the White 

Paper and conclusions from other 

reviews, FDA concluded that various 

dermatological conditions or lesions of 

the skin, mouth, and tongue were 

attributed to direct or indirect contact 

with dental amalgam, and may have 

been related to a pre-existing 

hypersensitivity or allergy to mercury 

and/or other metals. To help ensure that 

the device is not used in patients who 

are allergic to mercury, FDA is 

recommending that the labeling of the 

device contain a warning that the device 

contains mercury and a contraindication 

against use in persons with a known 

allergy to mercury. 

FDA disagrees that the mercury from 

dental amalgam plays a role in the 

pathogenesis of periodontal disease. 

Based on its review of the scientific 

literature on this subject (Refs. 71–75), 

FDA has concluded that the mercury in 

dental amalgam is not an etiological or 

aggravating agent for the initiation, 

propagation, or aggravation of any form 

of periodontitis. 

(Comment) Several comments 

suggested that the mercury in dental 

amalgam causes or contributes to 

chronic neurological or 

neurodegenerative diseases, such as 

Alzheimer’s disease, Parkinson’s 

disease, and autism. 

(Response) FDA discusses in detail in 

section I.A the available clinical 

information related to these diseases 

and its conclusions. In addition to the 

studies discussed in section I.A., and 

explained in the White Paper and 

Addendum reports (Refs. 10, 11), no 

evidence of neurodegenerative diseases 

have been reported in occupational 

cohorts exposed to much higher levels 

of mercury vapor in the workplace 

compared to the low levels in nonoccupational groups with exposure from 

amalgams. 

(Comment) One comment claimed 

that dental amalgam may cause kidney 

damage in children, as evidenced by a 

recent clinical trial (New England) (Ref. 

46) that showed that children with 

amalgam restorations had higher levels 

of microalbuminuria (protein in urine), 

which is a marker of kidney injury, than 

children with non-amalgam 

restorations. 

(Response) FDA disagrees with this 

comment. FDA reviewed the New 

England trial (Ref. 46) in the Addendum 

to the White Paper and concluded that, 

although microalbuminuria levels were 

higher in the amalgam treatment group, 

the levels of three other biomarkers of 

kidney injury were not different 

between the amalgam versus composite 

restoration groups. The authors of the 

study noted that they were unable to 

determine whether the increase in 

microalbuminuria was related to 

treatment or may have occurred by 

chance, since albuminuria may be 

caused by strenuous physical exercise, 

urinary tract infections, or other 

conditions with fever, or be related to 

orthostatic proteinuria (Ref. 46). 

However, in another children’s 

prospective trial (Casa Pia), there were 

no differences between the amalgam 

and composite groups with respect to 

the urinary excretion of microalbumin 

or albumin (Ref. 31), a biomarker of 

renal glomerular injury, and GST-alpha 

and GST-pi, two biomarkers of renal 

proximal and distal tubule injury, 

respectively (Ref. 47) (see also section 

I.A). 

D. Patient Information 

(Comment) Several comments stated 

that FDA should require dentists to 

inform their patients that dental 

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amalgam contains mercury, and to 

advise them of the risks and benefits of 

the device, as well as the various 

restoration choices available to them. 

Many comments expressed concern that 

the labeling information would be 

provided only to dentists and not to 

patients. Several comments suggested 

that informed consent should be 

obtained from patients before they are 

treated with the device. 

(Response) As a preliminary matter, 

FDA believes the comments that 

suggested that ‘‘informed consent’’ be 

obtained before patients receive dental 

amalgam were not using the term as it 

is used in 21 CFR part 50, which applies 

to the protection of human subjects in 

clinical investigations (for example, 

investigations of devices that have not 

been cleared or approved for marketing). 

Rather, these comments appear to be 

concerned about ensuring that patients 

are informed about the risks, benefits, 

and alternatives to dental amalgam. 

FDA recognizes that selection of an 

appropriate restorative material for an 

individual patient, and hence an 

appropriate treatment plan, is a complex 

matter that requires the expertise of the 

dental professional. In selecting the 

appropriate restorative material for an 

individual patient, the dentist routinely 

considers many factors, such as the 

patient’s oral health, the material 

properties of the various options, and 

the patient’s medical history, including 

whether the patient has a known allergy 

to mercury. 

FDA believes that the recommended 

labeling statements in the special 

controls guidance document will 

provide dentists with important 

information that will improve their 

understanding of the devices and help 

them make appropriate treatment 

decisions with their patients. In 

addition, FDA notes that dental 

amalgam is a prescription device and, 

therefore, patients cannot receive the 

device without the involvement of a 

learned intermediary, the dental 

professional. Based on the reasons 

described above, FDA has concluded 

that it is not necessary to require that 

dentists provide this information to 

patients in order to provide reasonable 

assurance of the safety and effectiveness 

of the device. 

E. Alternative Materials 

Several comments were submitted in 

response to FDA’s request for 

information on the relative costs and 

replacement lives of dental amalgam 

and alternative materials, particularly 

composite resins. 

(Comment) With respect to cost, one 

comment stated that composites cost 46 

percent more than equivalent amalgam 

restorations and are more likely to fail, 

resulting in the need for crowns on large 

surfaces. Another comment stated that 

alternative materials cost 20 percent 

more than amalgam restorations. One 

commenter stated that data from 2007 

indicate that the average fee submitted 

to insurance companies for one to four 

or more surfaces of dental amalgam 

ranged from $107 to $186, while the 

average submitted fee for composite 

resins ranged from $135 to $242 for the 

same surfaces. One comment stated that 

amalgam remains the best choice for 

deeper carious lesions of the posterior 

teeth and for patients seeking effective, 

lower cost dentistry. 

(Response) FDA agrees that, in 

general, composite resin restorations are 

more costly than dental amalgam 

restorations. 

(Comment) FDA received conflicting 

comments on the durability of 

composite resins versus dental 

amalgam. Some comments stated that 

composite resins are inferior to amalgam 

with respect to durability, stiffness, 

wear resistance, marginal stability, and 

service life, and that they must be 

replaced more frequently. One comment 

stated that amalgam fillings can last for 

35 years, while composites need to be 

replaced every 5 years. In contrast, other 

comments stated that amalgam is 

inferior to composites. For example, one 

comment stated that amalgam-filled 

teeth have a tendency to crack more 

frequently than composite-filled teeth, 

inevitably leading to more expensive 

restorations, such as crowns. The 

commenter stated further that composite 

resins better preserve the structural 

integrity of the tooth because they do 

not expand and because less natural 

tooth structure is removed in 

preparation for their placement. Other 

comments stated that the service lives of 

composite resins and dental amalgam 

are equivalent. One comment stated that 

the process for placing composite 

restorations is technique-sensitive and, 

if done properly, a composite 

restoration can last as long as an 

amalgam restoration. 

(Response) FDA believes that the 

durability of dental restorations is 

dependent on many factors related to 

material properties, the type and size of 

the restoration, the dentist’s skill, and 

patient use. According to the literature, 

the two primary reasons dental 

restorations fail are secondary caries (as 

the result of marginal leakage) and 

fracture. Studies have shown higher 

secondary caries rates for composite 

resins, but equivalent fracture rates for 

composite and amalgam restorations 

(Ref. 76). 

F. Need for Public Hearings 

(Comment) FDA received many 

comments on the proposed rule in 2002 

requesting the agency to hold a public 

hearing or advisory committee meeting 

on dental amalgam, noting that dental 

amalgam had not been discussed in an 

FDA public meeting since 1994. Many 

comments requested that individual 

consumers, consumer advocacy 

organizations, and scientists and health 

professionals opposed to the use of 

dental amalgam be included in such a 

meeting. 

(Response) FDA believes the concerns 

expressed by these comments were 

addressed in 2006 when FDA held a 

joint meeting of the Dental Products 

Panel and the Peripheral and Central 

Nervous Drugs Advisory Committee. 

One of the principal purposes of that 

meeting was to provide a transparent, 

public forum where all parties might 

share information. The panelists at the 

meeting were selected from a wide 

range of disciplines and interests, 

including neurology, dentistry, 

toxicology, statistics, epidemiology, and 

consumer advocacy. The 2006 meeting 

included an opportunity for the public 

to provide presentations, and a docket 

was opened to permit additional 

information to be submitted to the 

agency (Docket No. FDA–2008–N– 

0163). The 2006 Panel listened to 

presentations from more than 50 

members of the public and FDA’s 

presentation of its White Paper. At the 

conclusion of the meeting, the 2006 

Panel provided individual and panel 

recommendations to the agency. 

G. Accusations of FDA Bias 

(Comment) Several comments 

accused FDA of being biased in this 

rulemaking in support of the continued 

use of dental amalgam. The comments 

stated that the agency is too closely 

aligned with the interests of 

professional dental organizations and, 

as a result, has unfairly discounted 

evidence regarding the health risks 

presented by dental amalgam. 

(Response) FDA disagrees with the 

comments suggesting that it has been 

biased in its approach to regulating 

these devices. This final rule and the 

special controls guidance document 

reflect FDA’s careful and impartial 

consideration of all the comments and 

information it has received, the 

scientific information and safety 

assessments discussed previously, the 

White Paper and Addendum reports, 

and the adverse event reports submitted 

regarding these devices. 

FDA has been proactive in obtaining 

as much information as practicable 

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regarding the safety of these devices. As 

described previously, FDA has 

undertaken or supported several safety 

assessments since the early 1990s 

regarding dental amalgam. In 2006, in 

an effort to ensure a transparent, public 

forum for discussion, FDA convened a 

joint committee of panelists with 

diverse backgrounds, including 

neurology and toxicology experts, to 

consider FDA’s most recent review of 

the scientific literature related to dental 

amalgam (the White Paper) as well as 

presentations from members of the 

public. In response to the 

recommendations of the 2006 Panel, 

FDA updated its White Paper in the 

Addendum report. 

(Comment) Some comments suggested 

that FDA did not consider the report on 

mercury by the Agency for Toxic 

Substances and Disease Registry, and 

that FDA ignored the toxicological and 

adverse health effects identified in 

Toxicological Profiles for Mercury, 

which was published by the U.S. 

Department of Health and Human 

Services. 

(Response) FDA disagrees with the 

comments. FDA reviewed and evaluated 

both of these reports in preparing the 

White Paper (Ref. 10). 

H. Preemption 

(Comment) FDA received several 

comments requesting the agency to 

explain the preemptive effect of this 

rule on state requirements involving 

dental amalgam and on the tort liability 

of dentists. 

(Response) FDA has imposed a 

special control to address the risks of 

exposure to mercury, toxicity and 

adverse tissue reaction, corrosion and 

mechanical failure, and improper use 

presented by these devices. This special 

control creates ‘‘requirements’’ for the 

manufacturer’s labeling and other 

aspects of dental amalgam devices 

under 21 U.S.C. 360k, even though 

product sponsors have some flexibility 

in how they meet those requirements. 

Papike v. Tambrands, Inc., 107 F.3d 

737, 740–42 (9th Cir. 1997). With 

respect to the tort liability of dentists, 

the special control in this rule requires 

manufacturers to properly inform 

dentists about dental amalgam in the 

labeling, but does not impose any 

requirements on dentists. Dental 

amalgam is a prescription device, and 

properly informed dentists will be able 

to make the most appropriate treatment 

decisions for their patients, taking 

individual concerns into account. FDA 

does not intend to regulate the practice 

of dentistry. State consumer protection 

laws that concern the practice of 

dentistry, not manufacturer labeling, are 

therefore not implicated by this final 

rule. See Cal. Bus. & Prof. Code 

§§ 1648.10–1648.20 (requiring dentists 

to provide factual information to 

patients about dental amalgam); Maine 

(32 M.R.S. § 1094–C) (same); N.H. R.S.A. 

§ 317–A:38 (same); N.Y. C.L.S. E.C.L. 

§ 27–0926 (precluding dentists from 

using mercury in dentistry unless it is 

encapsulated for environmental 

reasons). 

I. Environmental Concerns 

(Comment) Many comments stated 

that dental amalgam should not be used 

because it is a toxic metal that pollutes 

the environment and frequently 

referenced concerns related to water and 

air pollution. Several comments stated, 

in general, that FDA has never prepared 

an Environmental Assessment for dental 

amalgam and should do so considering 

mercury is a bioaccumulative toxicant. 

One comment specifically addressed 

FDA requirements under the National 

Environmental Policy Act of 1969 

(NEPA). The comment stated that FDA 

has a statutory duty to prepare an 

Environmental Impact Statement (EIS) 

or, at a minimum, an Environmental 

Assessment (EA) before promulgating 

any final action relating to the 

classification of dental amalgam, 

reclassification of mercury or the 

issuance of a special control. Moreover, 

the comment characterized the 

categorical exclusion in 21 CFR 25.34(b) 

as being ‘‘overbroad’’ and seemed to 

fault FDA for not finding extraordinary 

circumstances in the context of this 

rulemaking. The comment cited to 

Louisiana v. Lee, 758 F.2d 1081 (5th Cir. 

1985), cert. denied, 475 U.S. 1044 (1986) 

as support for its assertion that an FDA 

action to classify or reclassify dental 

mercury devices does not perpetuate the 

status quo and has significant effects. 

The comment suggests that FDA must 

evaluate the continued introduction of 

mercury into the environment 

attributable to dental devices. 

(Response) Under the National 

Environmental Policy Act of 1969 

(NEPA), all Federal agencies must assess 

the environmental impact of any ‘‘major 

Federal action’’ they take (42 U.S.C. 

4332(C)). A regulation to classify or 

reclassify a device constitutes a major 

Federal action under NEPA (see 40 CFR 

1508.18). The Council on 

Environmental Quality (CEQ) is 

responsible for overseeing Federal 

efforts to comply with NEPA and issued 

regulations on procedural requirements 

of NEPA (40 CFR Parts 1500–1508). CEQ 

directs Federal agencies to adopt 

procedures, as necessary, to supplement 

the CEQ regulations (40 CFR 1507.3). 

FDA promulgated its supplemental 

NEPA regulations in 21 CFR Part 25. 

For major Federal actions 

‘‘significantly affecting the quality of the 

human environment,’’ an agency must 

prepare an Environmental Impact 

Statement (EIS) (see id.; 40 CFR 1501.4; 

21 CFR 25.22). If the action ‘‘may’’ have 

such a significant environmental effect, 

an agency must prepare an 

Environmental Assessment (EA) to 

provide sufficient evidence and analysis 

for the agency to determine whether to 

prepare an EIS or a finding of no 

significant impact (FONSI) (40 CFR 

1501.3; 21 CFR 25.20). 

However, agencies can establish 

categorical exclusions for categories of 

actions that do not individually or 

cumulatively have a significant effect on 

the human environment and for which, 

therefore, neither an EA nor an EIS is 

required (see 40 CFR 1508.4). FDA 

promulgated such an exclusion, under 

21 CFR 25.34(b), for agency actions that 

classify or reclassify a device and that 

may include the establishment of a 

special control, if the action will not 

result in increases in the existing levels 

of use of the device or changes in the 

intended use of the device or its 

substitutes. FDA considered the 

application of this categorical exclusion 

to its classification/reclassification 

decision in this final rule, and to the 

establishment of the special control for 

mercury, amalgam alloy, and dental 

amalgam. (Ref. 77) Consistent with its 

NEPA obligations, the agency 

considered whether there were any 

extraordinary circumstances that would 

preclude its reliance on this categorical 

exclusion for this final rule (agency 

procedures must ‘‘provide for 

extraordinary circumstances in which a 

normally excluded action may have a 

significant environmental effect’’ (40 

CFR 1508.4; see also 21 CFR 25.21)). 

The agency determined that the action 

it is taking in this final rule is 

appropriately categorically excluded 

under 21 CFR 25.34(b). 

These comments reflect a 

misunderstanding of the action FDA is 

taking in this final rule and it 

obligations under NEPA for such action. 

The comments presume that FDA has a 

general obligation under NEPA, in the 

context of promulgating this final rule, 

to assess the impacts of mercury on the 

environment and the effects of any 

continued introduction of mercury 

attributable to dental devices. FDA 

disagrees with such a presumption, 

particularly where there is ‘‘no 

reasonably close causal relationship’’ 

between the actions in the final rule and 

such general impacts. DOT v. Public 

Citizen, 541 U.S. 752, 767 (2004) 

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(rejecting a ‘‘but for’’ causal relationship 

as sufficient to require agency 

environmental review under NEPA) 

(citation omitted)). The comments 

ignore the scope of the action FDA is 

taking in this final rule and the 

categorical exclusion that applies to it. 

Specifically, FDA is classifying dental 

amalgam into class II, reclassifying 

mercury from class I to class II, and 

designating a special control to support 

the class II classifications of dental 

amalgam, mercury, and amalgam alloy 

(currently classified as class II). The 

action is being taken to establish 

sufficient regulatory controls that will 

provide reasonable assurance of the 

safety and effectiveness of these devices. 

This action does not constitute a 

decision to permit any individual’s 

particular use of any of these devices in 

the market. It simply provides a 

classification regulation establishing 

sufficient regulatory controls that will 

provide reasonable assurance of safety 

and effectiveness as to the particular 

class of these devices. The introduction 

into interstate commerce of amalgam 

alloy, mercury, or dental amalgam 

requires FDA clearance under section 

510(k) of the act (21 U.S.C. 360(k)). An 

FDA decision to clear a device under 

section 510(k) of the act would be a 

‘‘major Federal action’’ (as defined in 40 

CFR 1508.18) and would be 

independent of FDA’s action in this 

final rule. Thus, FDA would evaluate, 

independent of this final rule, its 

obligations under NEPA for a decision 

to clear a particular use of amalgam 

alloy, mercury, or dental amalgam in the 

context of a 510(k) submission. Such a 

decision is not before the agency in this 

final rule. Manufacturers currently or 

intending to market amalgam alloy, 

mercury, or dental amalgam are 

expected to comply with the 

requirements of special controls and 

address the issues of safety and 

effectiveness identified in the special 

controls guidance, either by following 

the recommendations in the guidance or 

by some other means that provides 

equivalent assurances of safety and 

effectiveness, on or before effective date 

of rule (see the DATES section of this 

document). 

Further, the reference in the comment 

to Louisiana v. Lee is misplaced. In that 

case, the court vacated a lower court’s 

judgment and remanded the case for 

more careful review to ascertain 

whether an environmental assessment 

and finding of no significant impact by 

the United States Army Corps of 

Engineers was reasonable. 758 F.2d 

1081 at 1086. To the extent the 

comment likens the issuance of permits 

that would allow for continued dredging 

of the Louisiana Gulf Coast area to a 

decision on a classification, the 

comparison is not on point. As 

previously stated, this final rule does 

not constitute a decision on a particular 

submission to ‘‘permit’’ any particular 

introduction into the environment of 

any of these devices. 

FDA appropriately focuses its 

environmental review in this final rule 

on its action to classify, reclassify, and 

establish a special control for amalgam 

alloy, mercury, and dental amalgam. 

FDA disagrees, as one comment asserts, 

that FDA is required to prepare an 

environmental assessment or an 

environmental impact statement under 

NEPA for this final rule. FDA has 

evaluated the application of the existing 

categorical exclusion in 21 CFR 25.34(b) 

to the actions it is taking in this final 

rule and concludes, based on the 

reasons set forth below, that it is proper 

to rely on that categorical exclusion for 

this final rule. 

In 1985, FDA finalized a categorical 

exclusion in 21 CFR 25.24(e)(2) for the 

‘‘classification or reclassification of a 

device under Part 860’’ (50 FR 16635 at 

16661; April 26, 1985). FDA identified 

this as a class of actions that would not 

result in the production or distribution 

of any substance, and therefore, would 

not result in the introduction of any 

substance into the environment. (44 FR 

71742 at 71745; December 11, 1979). In 

other words, changing the classification 

of a device from, e.g., class I to class II, 

would not, by itself, result in the 

introduction of any substance into the 

environment. Therefore, such an action 

would not normally require the 

preparation of an environmental 

assessment (44 FR 71742 at 71745; 

December 11, 1979). In 2005, FDA 

expanded the categorical exclusion for 

the classification and reclassification of 

devices to include, within its scope, an 

action that establishes special controls, 

if such action will not result in 

increases in the existing levels of use of 

the device or changes in the intended 

use of the device or its substitutes (70 

FR 69276; November 15, 2005). Thus, 

FDA would evaluate the application of 

the categorical exclusion for 

classification and reclassification 

decisions that include the establishment 

of special controls on a case-by-case 

basis to determine whether its action 

would result in increases in the existing 

levels of use or changes to the intended 

use of the device or its substitutes. FDA 

does not consider such a categorical 

exclusion to be ‘‘overbroad’’ as one 

comment asserts. 

FDA has determined that its action to 

classify dental amalgam, reclassify 

dental mercury, and to establish a 

special control are all within the scope 

of the categorical exclusion in 21 CFR 

25.34(b). This final rule reclassifies 

mercury from the lower risk class I to 

the higher risk class II and classifies 

dental amalgam as class II. The final 

rule does not change the requirements 

in place prior to this final rule and that 

remain in effect after this final rule 

publishes, e.g., premarket review and 

general controls. The change in 

classification alone does not result in 

the introduction of any substance into 

the environment, does not increase the 

existing levels of use, and does not 

change the intended use of these 

devices or their substitutes (Ref. 77). 

In addition, FDA undertook a careful 

review of the special control designated 

by this final rule to determine whether 

the special control would increase the 

existing levels of use or change the 

intended use of amalgam alloy, 

mercury, and dental amalgam or their 

substitutes. (Ref. 77) FDA has 

determined that the labeling 

recommendations in the special controls 

guidance imposed by the final rule 

would not result in increases in the 

existing levels of use of the devices or 

changes in the intended use of the 

devices or their substitutes. (Ref. 77) 

The labeling statements should help 

ensure that dentists are more fully 

informed regarding the devices. We 

have no basis to suggest or expect that 

the labeling recommendations would 

result in any increase in use of these 

devices or changes in the intended use 

of the devices or their substitutes. 

Further, FDA has determined that 

testing recommendations would not 

result in increases in the existing levels 

of use of the devices or changes in the 

intended use of the devices or their 

substitutes. (Ref. 77) None of the tests 

require additional specimens of dental 

amalgam, amalgam alloy, or mercury. 

The test for mercury requires only 

visual inspection, which can be 

performed using current inventory, i.e., 

without the need for any additional 

mercury for the test. The tests for dental 

amalgam and amalgam alloy, required 

by the final rule and that were not 

routinely performed prior to the final 

rule, would require approximately 2.2 

grams per product, which can be 

obtained from material used for a 

previous non-destructive test already 

routinely performed or from inventory 

needed for all testing. To the extent a 

manufacturer elects to procure 

additional product for the test, the 

amount is not significant. (Ref. 77) 

Moreover, the possibility a 

manufacturer would even elect to 

procure additional material for such 

tests is speculative. FDA found that its 

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33 Dental Amalgam: A Scientific Review and 

Recommended Public Health Service Strategy for 

Research, Education and Regulation; Public Health 

Service, U.S. Department of Health and Human 

Services, January 1993. 34Liu, J. et al., ‘‘Toxic effects of metals,’’ Casarett 

& Doull’s Toxicology: The Basic Science of Poisons, 

Chapter 23, pp. 931–979, McGraw-Hill Medical, 

New York, New York, 2008. 

Clarkson, T.W. et al., ‘‘The Toxicology of Mercury 

and Its Chemical Compounds,’’ Critical Reviews in 

Toxicology, Vol. 36, pp. 609–662, 2006. 35 De Rouen, T. et al., ‘‘Neurobehavioral Effects of 

Dental Amalgam in Children, A Randomized 

Clinical Trial,’’ Journal of the American Medical 

Association, Vol. 295, 1784–1792, No. 15, April 19, 

2006. 

Bellinger, D.C. et al., ‘‘Neuropsychological and 

Renal Effects of Dental Amalgam in Children: A 

Randomized Clinical Trial,’’ Journal of the 

American Medical Association, Vol. 295, No. 15, 

April 19, 2006, 1775–1783, 2006. 

Barregard, L. et al., ‘‘Renal Effects of Dental 

Amalgam in Children: The New England Children’s 

Amalgam Trial,’’ Environmental Health 

Perspectives, Volume 116, 394–399, No. 3, March 

2008. 

Woods, J.S. et al., ‘‘Biomarkers of Kidney 

Integrity in Children and Adolescents With Dental 

Amalgam Mercury Exposure: Findings From the 

Casa Pia Children’s Amalgam Trial,’’ Environmental 

Research, Vol. 108, pp. 393–399, 2008. 

Lauterbach, M. et al., ‘‘Neurological Outcomes in 

Children With and Without Amalgam-Related 

Mercury Exposure: Seven Years of Longitudinal 

Observations in a Randomized Trial,’’ Journal of the 

American Dental Association, Vol. 139, 138–145, 

February 2008. 

action in this final rule to classify dental 

amalgam into class II, reclassify mercury 

from class I to class II, and to establish 

a special control for dental amalgam, 

mercury, and amalgam alloy does not 

significantly affect the quality of the 

human environment and that there are 

no extraordinary circumstances (Ref. 

77). (See also, Utah Envtl. Cong. v. 

Bosworth, 443 F.3d 732 (10th Cir. 2006) 

(stating an extraordinary circumstance 

exists ‘‘only where a proposed action 

‘may have a significant environmental 

effect.’ ’’) (citations omitted)). Based on 

FDA’s review, it concludes that this 

final rule is appropriately categorically 

excluded under 21 CFR 25.34(b), and 

therefore, does not require an 

environmental assessment or an 

environmental impact statement. 

(Comment) Some comments suggested 

that dental amalgam manufacturers 

should provide an environmental 

impact statement to prove that dental 

amalgams are environmentally safe. 

(Response) Under 21 CFR 25.40, FDA 

generally requires an applicant to 

prepare an environmental assessment 

for any action that is not categorically 

excluded. FDA would determine, for 

each 510(k) submission the agency may 

receive, what environmental documents 

may be necessary to comply with the 

agency’s obligations under NEPA. 

IV. Environmental Impact 

The agency has considered the 

environmental effects of this final rule 

and has determined under categorical 

exclusion 21 CFR 25.34(b) that this 

action is of a type that does not 

individually or cumulatively have a 

significant effect on the human 

environment. Therefore, neither an 

environmental assessment nor an 

environmental impact statement is 

required (Ref. 77). 

V. Analysis of Impacts 

A. Introduction 

FDA has examined the impacts of the 

final rule under Executive Order 12866, 

the Regulatory Flexibility Act (5 U.S.C. 

601–612), and the Unfunded Mandates 

Reform Act of 1995 (Pub. L. 104–4). 

Executive Order 12866 directs agencies 

to assess all costs and benefits of 

available regulatory alternatives and, 

when regulation is necessary, to select 

regulatory approaches that maximize 

net benefits (including potential 

economic, environmental, public health 

and safety, and other advantages; 

distributive impacts; and equity). The 

agency believes this final rule is a not 

an economically significant regulatory 

action under the Executive order. 

The Regulatory Flexibility Act 

requires agencies to analyze regulatory 

options that would minimize any 

significant impact of a rule on small 

entities. Because of the relatively minor 

direct costs to entities attributable to 

this final rule, the agency certifies that 

the final rule will not have a significant 

economic impact on a substantial 

number of small entities. 

Section 202(a) of the Unfunded 

Mandates Reform Act of 1995 requires 

that agencies prepare a written 

statement, which includes an 

assessment of anticipated costs and 

benefits, before proposing ‘‘any rule that 

includes any Federal mandates that may 

result in the expenditure by State, local, 

and Tribal governments, in the 

aggregate, or by the private sector, of 

$100,000,000 or more (adjusted 

annually for inflation) in any one year.’’ 

The current threshold after adjustment 

for inflation is $133 million, using the 

most current (2008) Implicit Price 

Deflator of the Gross Domestic Product. 

FDA does not expect this final rule to 

result in a 1-year expenditure that could 

exceed this amount. 

B. Summary of Economic Impacts 

The final rule classifies dental 

amalgam into class II, reclassifies 

mercury from class I to class II, and 

designates a special control to support 

the class II classifications of these two 

devices, as well as the current class II 

classification of amalgam alloy. Today’s 

action classifies the three devices in a 

single regulation. The special control for 

the devices is a guidance document 

entitled ‘‘Class II Special Controls 

Guidance Document: Dental Amalgam, 

Mercury, and Amalgam Alloy,’’ which 

includes labeling recommendations as 

well as quality control procedures. 

Conforming to the special control will 

require few additional resources at the 

manufacturing stage as well as costs to 

FDA for administering the final 

regulation. Some dentists may consider 

the information-for-use statement, along 

with many other factors, when making 

treatment decisions for their patients. A 

small number of dentists may use dental 

amalgam for some patients for whom 

they may not have used the device 

previously, and decide not to use the 

device for other patients for whom they 

may have used the device. However, 

any change away from use of dental 

amalgam is likely to result in negative 

public health outcomes (delayed dental 

treatments or increased costs of 

treatment). While there would be a 

decrease in mercury exposure, there is 

no evidence that there would be any 

reduction in adverse affects associated 

with mercury. Conversely, any change 

towards use of dental amalgam is likely 

to result in positive public health 

outcomes or decreased costs of 

treatment. 

C. Objective and Need of the Final Rule 

The purpose of this final rule is to 

classify dental amalgam, reclassify 

mercury, and designate a special control 

to support the class II classification of 

dental amalgam, mercury, and amalgam 

alloy as required by section 513 of the 

act. The special control for the device is 

a guidance document with composition 

and performance data, biocompatibility, 

and labeling recommendations. One of 

the labeling recommendations is the 

following information for use: 

Dental amalgam has been demonstrated to 

be an effective restorative material that has 

benefits in terms of strength, marginal 

integrity, suitability for large occlusal 

surfaces, and durability.33 Dental amalgam 

also releases low levels of mercury vapor, a 

chemical that at high exposure levels is welldocumented to cause neurological and renal 

adverse health effects.34 Mercury vapor 

concentrations are highest immediately after 

placement and removal of dental amalgam 

but decline thereafter. 

Clinical studies have not established a 

causal link between dental amalgam and 

adverse health effects in adults and children 

age six and older. In addition, two clinical 

trials in children aged six and older did not 

find neurological or renal injury associated 

with amalgam use.35

The developing neurological systems in 

fetuses and young children may be more 

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36Agency for Toxic Substances and Disease 

Registry (ATSDR) and Research Triangle Institute, 

Toxicological Profile for Mercury, U.S. Dept. of 

Health and Human Services, Public Health Service, 

Atlanta, Georgia, 1999. 

United States Environmental Protection Agency 

(EPA), ‘‘Integrated Risk Information System (IRIS) 

Screening-Level literature Review’’—Mercury, 

elemental, 2002. 

sensitive to the neurotoxic effects of mercury 

vapor. Very limited to no clinical information 

is available regarding long-term health 

outcomes in pregnant women and their 

developing fetuses, and children under the 

age of six, including infants who are 

breastfed. 

The Agency for Toxic Substances and 

Disease Registry’s (ATSDR) and the 

Environmental Protection Agency (EPA) have 

established levels of exposure for mercury 

vapor that are intended to be highly 

protective against adverse health effects, 

including for sensitive subpopulations such 

as pregnant women and their developing 

fetuses, breastfed infants, and children under 

age six.36 Exceeding these levels does not 

necessarily mean that any adverse effects will 

occur. 

FDA has found that scientific studies using 

the most reliable methods have shown that 

dental amalgam exposes adults to amounts of 

elemental mercury vapor below or 

approximately equivalent to the protective 

levels of exposure identified by ATSDR and 

EPA. Based on these findings and the clinical 

data, FDA has concluded that exposures to 

mercury vapor from dental amalgam do not 

put individuals age six and older at risk for 

mercury-associated adverse health effects. 

Taking into account factors such as the 

number and size of teeth and respiratory 

volumes and rates, FDA estimates that the 

estimated daily dose of mercury in children 

under age six with dental amalgams is lower 

than the estimated daily adult dose. The 

exposures to children would therefore be 

lower than the protective levels of exposure 

identified by ATSDR and EPA. 

In addition, the estimated concentration of 

mercury in breast milk attributable to dental 

amalgam is an order of magnitude below the 

EPA protective reference dose for oral 

exposure to inorganic mercury. FDA has 

concluded that the existing data support a 

finding that infants are not at risk for adverse 

health effects from the breast milk of women 

exposed to mercury vapors from dental 

amalgam. 

The guidance also recommends that 

the labeling of dental amalgam and 

mercury devices include warnings about 

potential exposure to mercury, 

including: ‘‘WARNING: CONTAINS 

MERCURY’’ and ‘‘harmful if vapors are 

inhaled.’’ The labeling 

recommendations also include the 

following contraindication: ‘‘Do not use 

in persons with a known mercury 

allergy.’’ In addition, the special 

controls guidance document includes 

recommendations regarding 

composition and performance data, and 

biocompatibility testing. 

The need for this regulation stems 

from the current poor distribution of 

accurate information about exposure to 

mercury (Hg) through dental amalgam. 

The special control imposed by this 

final rule will ensure that dentists are 

reminded that dental amalgam contains 

mercury, and will provide them with 

FDA’s assessment of the most current, 

best available information regarding use 

of the device in various patient groups. 

D. Risk 

Mercury poisoning is a disease caused 

by exposure to mercury or its 

compounds. The most common 

exposure is to organic mercury through 

fish consumption. Elemental mercury 

may be inhaled or absorbed through the 

skin and is used for dental restorations 

as amalgam. Toxic effects of mercury, 

depending on the level of exposure, 

include damage to the brain, kidneys, 

and lungs, with symptoms that include 

sensory impairment, disturbed 

sensation, and lack of coordination. 

Elemental mercury is primarily 

associated with neurologic toxicity (Ref. 

78), although most cases do not have 

any noticeable physiological effects. 

Table 2 of this document shows 

reported elemental mercury exposures 

and treatments for 2005–2007. 

TABLE 1—ELEMENTAL MERCURY EXPOSURES AND TREATMENT OUTCOMES

Year 

Number of 

reported 

exposures 

Number 

seeking 

treatment 

No adverse 

outcome 

Minor adverse 

outcome 

Moderate 

adverse 

outcome 

Major adverse 

outcome Death 

2005 ................. 2,786 909 747 99 55 6 2 

2006 ................. 2,336 854 767 66 20 1 0 

2007 ................. 2,319 672 576 55 38 3 0 

Total .......... 7,441 2,435 2,090 220 113 10 2 

Percentage ....... ........................ 100 .0 85 .83 9 .03 4 .64 0 .41 0 .08 

Source: American Association of Poison Control Centers (Refs. 79, 80, and 81). 

Dental amalgam has not been shown 

to cause mercury poisoning and no data 

show a causal effect of dental amalgam 

for any adverse health effects (except in 

a small number of patients with a 

known allergy to mercury). Dental 

amalgam does contain mercury, 

although in quantities much smaller 

than those associated with the adverse 

outcomes summarized in table 2 of this 

document. 

Dental amalgam has been used to 

restore decayed teeth since the 1890s in 

the United States, although early 

prototypes were available from the 

1830s. Amalgam is an alloy that is about 

50% mercury (usually combined with 

silver, tin, or copper) and is one of 

several potential materials used to treat 

dental caries. Over the last 15 years 

(1993–2008), we estimate that 

approximately 900 million restorations 

have been performed using dental 

amalgam, although the annual number 

of all restorations, as well as amalgam 

restorations, has been decreasing (see 

Section V.E). According to Delta Dental 

Insurance (Ref. 82), the typical amalgam 

restoration has 1.8 surfaces (a ‘‘surface’’ 

is a measure of exposed surface of the 

restoration). Research has indicated that 

each surface of an amalgam restoration 

releases approximately 0.534 μg Hg/day 

(Ref. 83). With a baseline of 900 million 

amalgams and 1.8 surfaces per amalgam, 

we estimate 865 million μg Hg/day were 

released by amalgams (900 million 

amalgams × 1.8 surfaces per amalgam × 

0.534 μg Hg/day per surface) during 

2008. 

We are unable to estimate possible 

changes in exposure to mercury that 

may result from this rule. Dentists may 

use dental amalgam for some patients 

for whom they may not have used the 

device previously, and decide not to use 

the device for other patients for whom 

they may have used the device. 

However, any change away from use of 

dental amalgam is likely to result in 

negative public health outcomes 

(delayed dental treatments or increased 

costs of treatment); while there would 

be a decrease in mercury exposure, 

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there is no evidence that there would be 

any reduction in adverse effects 

associated with mercury. Conversely, 

any change toward use of dental 

amalgam is likely to result in positive 

public health outcomes (fewer delayed 

dental treatments or decreased costs of 

treatment). 

E. Baseline in the Absence of the Final 

Rule 

During 2008, there were an estimated 

154.1 million dental restorations in the 

United States (Ref. 84). This number 

represents a decrease of almost 12 

million restorations from 2005, with the 

decrease associated with better dental 

care. We assume that recent trends to 

reduce the use of dental amalgam as a 

restorative material will continue as 

patients and dentists take advantage of 

improved alternative materials for 

restorative and cosmetic purposes. 

Table 2 of this document shows 

projected annual restorations and 

annual amalgam restorations expected 

for the 15-year evaluation period. 

TABLE 2—PROJECTED ANNUAL DENTAL RESTORATIONS

[In millions] 

Evaluation year Total U.S. population Total restoration Amalgam restorations Other restorations 

2009 ................................................................. 307.2 149.0 50.5 98.5 

2010 ................................................................. 310.2 145.0 49.0 96.0 

2011 ................................................................. 313.2 141.0 47.6 93.5 

2012 ................................................................. 316.3 137.2 46.2 91.0 

2013 ................................................................. 319.3 133.4 44.8 88.5 

2014 ................................................................. 322.4 129.7 43.5 86.2 

2015 ................................................................. 325.5 126.1 42.2 83.9 

2016 ................................................................. 328.7 122.6 41.0 81.6 

2017 ................................................................. 331.8 119.1 39.8 79.4 

2018 ................................................................. 335.0 115.8 38.6 77.2 

2019 ................................................................. 338.2 112.5 37.5 75.0 

2020 ................................................................. 341.4 109.4 36.4 72.9 

2021 ................................................................. 344.6 106.3 35.4 70.9 

2022 ................................................................. 347.8 103.3 34.4 68.9 

2023 ................................................................. 351.0 100.3 33.4 67.0 

The population of the United States is 

projected to increase at an annual rate 

of about 0.9 percent over this period and 

dental restorations as a whole, as well 

as amalgam restorations, are expected to 

decrease by about 1.9 percent per year. 

This projection is based on the expected 

age distribution of the population as 

reported by the Census Bureau and 

historical rates of restorations by agecohort. For example, the population 

between the ages of 0–4 was about 20.3 

million in 2005, during which year 

3,339,000 restorations were conducted 

for this age cohort, for an average of 0.16 

restorations per capita. The Census 

Bureau projected that there will be 

about 20.9 million in the population 

aged 0–4 in 2009. Using the per capita 

rate of restorations, we expect there to 

be 3,344,000 restorations for this age 

group. The distributions of restoration 

by material and by age groups were 

summed for each year to result in the 

estimates shown in table 2 of this 

document. 

As an approximation of the total 

number of patients in specific 

populations who might be expected to 

be more vulnerable to mercury 

(pregnant women and their fetuses, 

children under the age of six, including 

those who are breastfed), we use the 

total number of pregnant and lactating 

women and children under six as the 

targeted or special populations in this 

analysis. According to the Agency for 

Toxic Substances and Disease Registry 

(Ref. 85), very young children are more 

sensitive to mercury than adults. 

Mercury in a mother’s body can pass to 

the fetus and may accumulate there 

(Ref. 85), and a nursing infant may be 

exposed to inorganic mercury through 

breast milk. Because of these 

sensitivities, we projected dental 

amalgam restorations for children under 

the age of 6, as well as for pregnant and 

lactating females ages 15–44 based on 

reporting from the American Dental 

Association (ADA) and projections from 

the Bureau of Census. The number of 

pregnant women was obtained from the 

National Center of Health Statistics for 

2004 (Ref. 86). The rate of pregnancy 

among women between the ages of 15 

and 44 for 2004 (0.1036) was used to 

project future annual pregnancies. 

Approximately two-thirds of all live 

births breast feed at least once (Ref. 87). 

Therefore, we have estimated that twothirds of the previous years’ live births 

account for lactating women. The 

number of children under the age of 6 

was obtained from Census projections. 

We could not obtain information on the 

potential number of other affected subpopulations but believe they could 

reasonably be accounted for in these 

projections, which include practically 

all the affected persons. Table 3 of this 

document shows these projections. 

TABLE 3—PROJECTED AMALGAM RESTORATIONS FOR SPECIFIC POPULATIONS

[In millions] 

Evaluation year 

Number of 

pregnant and 

lactating women 

Total children 

under the age 

of 6 

Total amalgam 

restorations 

Total amalgam in 

pregnant and 

lactating women 

Total amalgam in 

children under 6 

Total amalgam 

restorations in 

sensitive subpopulations 

2009 ................................. 9.22 25.1 50.5 1.8 2.6 4.4 

2010 ................................. 9.23 25.3 49.0 1.8 2.5 4.3 

2011 ................................. 9.27 25.5 47.6 1.7 2.5 4.2 

2012 ................................. 9.29 25.7 46.2 1.6 2.4 4.0 

2013 ................................. 9.32 26.0 44.8 1.6 2.3 3.9 

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TABLE 3—PROJECTED AMALGAM RESTORATIONS FOR SPECIFIC POPULATIONS—Continued 

[In millions] 

Evaluation year 

Number of 

pregnant and 

lactating women 

Total children 

under the age 

of 6 

Total amalgam 

restorations 

Total amalgam in 

pregnant and 

lactating women 

Total amalgam in 

children under 6 

Total amalgam 

restorations in 

sensitive subpopulations 

2014 ................................. 9.37 26.2 43.5 1.5 2.3 3.8 

2015 ................................. 9.41 26.4 42.2 1.5 2.2 3.7 

2016 ................................. 9.44 26.7 41.0 1.4 2.1 3.5 

2017 ................................. 9.49 26.9 39.8 1.4 2.1 3.5 

2018 ................................. 9.55 27.1 38.6 1.3 2.0 3.3 

2019 ................................. 9.62 27.2 37.5 1.3 2.0 3.3 

2020 ................................. 9.70 27.4 36.4 1.3 1.9 3.2 

2021 ................................. 9.78 27.6 35.4 1.2 1.8 3.0 

2022 ................................. 9.93 27.7 34.4 1.2 1.8 3.0 

2023 ................................. 10.04 27.9 33.4 1.2 1.7 2.9 

Because the annual use of dental 

amalgam for restorations is expected to 

continue to decrease, the exposures of 

these sub-populations to amalgam are 

also expected to decrease along with 

exposures in the population age six and 

older. We model the expected 

contribution per day of amalgam for the 

evaluation period in table 4 of this 

document. These projections are based 

on the decreasing number of amalgam 

restorations expected as replacements. 

During the period 1993–2008, according 

to data supplied by the ADA, 

approximately 60 million annual 

restorations used amalgam for a total of 

900 million current amalgam 

restorations in place. In the absence of 

the final rule, we project only 50.5 

million new amalgam restorations 

during 2009, down from 60 million from 

1993, resulting in only 890.5 million 

amalgam restorations for the entire 

population (900 million restorations in 

place + 50.5 new restorations during 

year 1 ¥ 60 million restorations from 

1993). Therefore, the daily potential 

exposure to mercury vapor originating 

from dental amalgam is expected to 

decrease gradually in the absence of the 

final rule. 

TABLE 4—PROJECTED TOTAL μg Hg 

PER DAY FROM DENTAL AMALGAM

IN THE ABSENCE OF THE FINAL RULE

[In millions] 

Evaluation year 

Number 

of amalgam restorations 

in place 

Number 

of annual 

amalgam 

restorations 

Micrograms 

(μg) of 

mercury 

(Hg) per 

day 

2009 ..... 890.5 50.5 856 

2010 ..... 879.5 49.0 845 

2011 ..... 867.1 47.6 833 

2012 ..... 853.3 46.2 820 

2013 ..... 838.1 44.8 806 

2014 ..... 821.6 43.5 790 

2015 ..... 803.8 42.2 772 

TABLE 4—PROJECTED TOTAL μg Hg 

PER DAY FROM DENTAL AMALGAM

IN THE ABSENCE OF THE FINAL

RULE—Continued 

[In millions] 

Evaluation year 

Number 

of amalgam restorations 

in place 

Number 

of annual 

amalgam 

restorations 

Micrograms 

(μg) of 

mercury 

(Hg) per 

day 

2016 ..... 784.8 41.0 754 

2017 ..... 764.6 39.8 735 

2018 ..... 743.2 38.6 714 

2019 ..... 720.7 37.5 693 

2020 ..... 697.1 36.4 670 

2021 ..... 672.5 35.4 646 

2022 ..... 646.9 34.4 622 

2023 ..... 620.3 33.4 596 

Table 4 of this document includes 

estimates of projected levels of mercury 

per day associated with the expected 

number of amalgams in place. Each 

amalgam is assumed to have 1.8 

surfaces and release 0.534 μg Hg per day 

per surface. 

F. The Final Rule 

This final rule will classify dental 

amalgam as class II, reclassify mercury 

from class I to class II, and designate a 

special control to support the class II 

classifications of these class II devices, 

as well as the current class II 

classification of amalgam alloy. All 

three devices will now be classified in 

a single regulation. Under Class II, these 

devices will be subject to a special 

control. In this case, we are designating 

as the special control a guidance 

document (with composition and 

performance data, biocompatibility 

testing, and labeling recommendations). 

The guidance document provides for 

some increased testing requirements 

that will ensure the composition of the 

amalgam as well as labeling 

recommendations. Specific additional 

tests in the guidance document include 

particle size distribution assays and 

corrosion testing that are not typically 

currently conducted by manufacturers. 

The labeling recommendations include 

a warning that dental amalgam contains 

mercury and provide information for 

use explaining that, although there are 

very limited to no clinical information 

available regarding long-term health 

outcomes in pregnant women and their 

developing fetuses, and children under 

the age of six, including infants who are 

breastfed, the estimated concentration of 

mercury in breastmilk attributable to 

dental amalgam exposure is low and is 

an order of magnitude below the EPA 

protective reference dose for oral 

exposure to inorganic mercury. The 

estimated daily dose of mercury in 

children under age 6 with dental 

amalgams is also low and at or below 

the ATSDR and EPA protective 

reference levels. 

G. Costs of the Final Rule 

FDA is required by statute to classify 

devices (21 U.S.C. 360c). This final rule 

classifies dental amalgam into Class II 

and reclassifies dental mercury 

(hereinafter ‘‘mercury’’) from Class I to 

Class II. Importantly, the rule also 

establishes special controls for dental 

amalgam, mercury, and amalgam alloy 

(mercury and amalgam alloy are 

combined to form dental amalgam). 

The costs of the final rule are the costs 

of complying with and administrating 

the special control (including testing 

and labeling costs, and FDA 

administration costs). 

The special controls guidance 

referenced in this final rule 

recommends that dental amalgam, 

mercury, and amalgam alloy be subject 

to periodic assays to demonstrate 

physical properties. Two of these assays 

are not routinely conducted and, 

consequently, would constitute 

additional expenses. In addition, the 

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special controls guidance recommends 

that the labeling state that the device 

contains mercury, that it should not be 

used in persons with a known allergy to 

mercury, and that data are limited 

regarding long term outcomes in certain 

populations. These labeling revisions 

are also additional requirements for 

manufacturers. 

1. Manufacturing Costs 

a. Testing Costs 

FDA records indicate the final rule 

will affect 50 separate products 

manufactured by 16 companies. These 

companies are classified in the Dental 

Equipment and Supplies Industry 

(NAICS 339114) by the Census of 

Manufacturers (NAICS is the North 

American Industry Classification 

System). 

The special controls guidance 

document that is part of this final rule 

includes two recommended quality 

control assays that are not routinely 

conducted by manufacturers. These 

assays are particle size distribution 

testing and corrosion products 

identification. While some of the 16 

manufacturers may use in-house 

laboratories to conduct these tests, if 

additional equipment is needed they are 

more likely to use contract laboratories. 

Discussions with contract laboratories 

showed that estimated costs for 

conducting assays of these types ranged 

between $35 and $150 per test with a 

typical test costing approximately $75. 

It is unclear how frequently these 

tests would be conducted. The current 

guidance recommends that tests be 

conducted once before marketing. 

However, we expect manufacturers to 

test each of their 50 marketed products 

at least once per year to ensure product 

quality. Therefore, the expected annual 

cost of conducting these additional tests 

equals $7,500 per year (50 products 

times 2 tests times $75). 

b. Labeling Costs Associated With the 

Final Rule 

The recommended labeling controls 

included in this final rule will result in 

enhanced labeling for dental amalgam 

devices. Specifically, the guidance 

recommends that the labeling for this 

product state that the device contains 

mercury, that it should not be used in 

persons with a known allergy to 

mercury, and that current scientific 

evidence indicates there is no 

connection between the device and 

adverse events in the population age six 

and older. The label also informs 

dentists that the clinical data are limited 

regarding long term outcomes in certain 

patients who might be expected to be 

more sensitive to the effects of mercury. 

We expect that each of the 50 

products currently marketed will 

develop a new label that includes this 

information. The cost of developing new 

artwork, label design, regulatory review, 

production, and application was 

estimated based on a labeling cost 

model developed by the Eastern 

Research Group (Ref. 88) and updated to 

2008. Overall, the cost of developing a 

new label using these guidelines is 

estimated to be approximately $2,000 

per label. Each of the 50 products 

marketed by 16 manufacturers is 

expected to have a revised label due to 

this requirement and result in a total 

one-time labeling cost of $100,000 (50 

products times $2,000). 

c. Increased Manufacturing Costs 

The total increased manufacturing 

costs of this final rule are $107,500 in 

the first evaluation year and $7,500 per 

year thereafter. The present value over 

15 years is $186,600 (3 percent discount 

rate) or $161,800 (7 percent discount 

rate). 

2. Costs of FDA Regulatory Oversight 

Although FDA currently regulates 

dental amalgam, the reclassification 

from this final rule is likely to increase 

oversight. Label review will likely be 

more rigorous and inspections will 

entail review of more testing data. Any 

reviews of marketing applications will 

be more rigorous and there are likely to 

be increases in the number of marketing 

applications submitted for review 

(although we have not estimated any 

such increase). In addition, FDA can 

anticipate additional interest in these 

products, which will probably require 

resources to respond to consumer and 

media requests for information. These 

activities are not likely to consume more 

than 30 minutes of full-time equivalent 

(FTEs) per product per year, or 

approximately 26 hours of resources. 

The estimated cost of an FDA FTE is 

approximately $130,000 per year, or 

about $64.75 per hour. (This estimate 

includes salary, benefits, overhead, and 

support). Therefore, the increased use of 

FDA resources due to the final rule is 

only approximately $1,700 per year (26 

hours times $64.75). The present values 

of 15 years of this cost equal $20,300 

(using 3 percent annual discount rate) 

and $15,500 (using 7 percent annual 

discount rate). 

3. Total Costs 

Table 5 of this document shows the 

estimated present value of costs and the 

annualized costs of the final rule by 

type. Testing costs and the costs of FDA 

administration are annual recurring 

costs. While the present values of these 

costs differ by discount rate, the 

annualized costs are not affected by 

discount rates. 

TABLE 5—PRESENT VALUE AND ANNUALIZED COSTS OF FINAL RULE

Present value 

at 3 percent 

Present value 

at 7 percent 

Annualized 

value at 

3 percent 

Annualized 

value at 

7 percent 

Labeling Cost ................................................................................................... $100,000 $100,000 $8,400 $10,100 

Testing Cost ..................................................................................................... 89,500 68,300 7,500 7,500 

Cost of FDA Administration ............................................................................. 20,300 15,500 1,700 1,700 

Total Cost ................................................................................................. 209,800 183,800 17,600 19,300 

H. Potential Public Health Effects of the 

Final Rule 

The recommended information for 

use statement will provide dentists with 

current information to help them make 

treatment decisions for their patients. 

We expect that dentists will consider 

that information, along with other 

factors, when making treatment 

decisions for their patients. Dentists 

may use dental amalgam for some 

patients for whom they may not have 

used the device previously, and decide 

not to use the device for other patients 

for whom they may have used the 

device. However, any change away from 

use of dental amalgam is likely to result 

in negative public health outcomes 

(delayed dental treatments or increased 

costs of treatment); while there would 

be a decrease in mercury exposure, 

there is no evidence that there would be 

any reduction in adverse effects 

associated with mercury. Conversely, 

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any change toward use of dental 

amalgam is likely to result in positive 

public health outcomes (fewer delayed 

dental treatments or decreased costs of 

treatment). 

I. Alternatives to the Final Rule 

The principal regulatory alternatives 

considered were as follows: (1) No new 

regulatory action, (2) Class II but with 

other special controls, (3) 

reclassification to Class III, and (4) ban 

the use of mercury in dental 

restorations. 

1. No New Regulatory Action 

No new regulatory action is the 

projected baseline we use to estimate 

the effects of the other options. By 

definition, there are no costs or public 

health effects associated with the 

baseline. 

2. Class II But With Other Special 

Controls 

This alternative would retain Class II 

but calls for different special controls. 

While deciding the type of special 

controls best suited for this device, we 

considered many different options. For 

example, we considered a labeling 

requirement that would require dentists 

to inform patients of the presence of 

mercury in dental amalgam and discuss 

treatment options and a special controls 

guidance document with labeling 

recommendations. Whatever the special 

controls in this alternative, the result 

would be that patients would get direct 

information that would include the 

presence of mercury in amalgam. The 

costs of this alternative would include 

the opportunity costs both dentists and 

patients of discussing treatment options, 

costs of alternative restorative materials, 

potentially delayed or deferred 

treatments, the cost of periodic testing 

by manufacturers, and the cost of FDA 

administration. There would be an 

expected reduction in mercury exposure 

and some potential reduction in anxiety 

for patients who would choose 

alternative materials with this 

information and after consultation with 

dentists. The costs and effects of this 

alternative are shown in table 6 of this 

document. 

TABLE 6—PRESENT VALUE AND ANNUALIZED EFFECTS OF ALTERNATIVE LABELING

Present value—3% Present value—7% Annualized value—3% Annualized value—7% 

Costs (In millions) .......................................... $2,433 to $6,563 ........ $1,932 to $4,948 ........ $208 to $550 .............. $212 to $543. 

Reduced Mercury Exposures (in million of μg 

Hg per day).

0 to 153.2 ................... 0 to 109.5 ................... 0 to 12.8 ..................... 0 to 12.0. 

Delayed Dental Treatments ........................... 0 to 990,000 ............... 0 to 813,000 ............... 0 to 83,000 ................. 0 to 89,000. 

The ranges shown in Table 6 show the 

uncertainty of how patients and dentists 

may be expected to react to information 

and differences in the durability of 

alternative materials. The estimates and 

ranges shown in table 6 include the 

effects of the higher costs of alternative 

materials, ranges of expected useful life 

of alternative materials, opportunity 

costs of dentists providing counseling, 

opportunity costs of patients, different 

durations of counseling, different 

expected reactions by patients to the 

information that amalgam contains 

mercury (based on market response of 

tuna consumers), and ranges of 

estimates of price elasticities of demand 

for dental services. The ranges are 

shown to address a wide range of 

potential alternative special controls 

that we did not select. 

3. Reclassification to Class III 

Class III classification of these 

products would require that 

manufacturers obtain premarket 

approval for dental amalgam, mercury, 

and amalgam alloy. The most likely 

effect of this alternative would be that 

marketers would choose to withdraw 

their products from the market rather 

than incur the costs and resources 

necessary to collect safety and 

effectiveness data to support premarket 

approval applications. The effects of 

this regulatory alternative are probably 

equivalent to a ban on the use of 

mercury in restorations and should be 

equal to the estimated impacts 

discussed for Alternative 4. 

4. Ban the Use of Mercury in Dental 

Restorations 

Another alternative is to ban dental 

amalgam. The ban would not give 

consumers a choice with respect to the 

use of dental amalgam. All consumers 

would be forced to use alternative 

materials or defer treatment for dental 

caries. The costs and effects of a ban are 

shown in tables 7 and 8 of this 

document. While the estimated number 

of delayed dental caries treatments that 

may result from a ban are not included 

in table 7, we consider them to 

represent negative public health effects. 

Any delay in dental treatment would 

likely lead to further deterioration and 

patient discomfort. However, there are 

no empirical data to suggest how long 

a delay in treatment would typify the 

response to a ban or what the social 

costs of delayed (or avoided) dental 

treatment would be. This negative 

public health outcome should be 

considered an additional non-quantified 

cost. The annualized public health 

effects appear equal for both discount 

rates due to rounding to the nearest 

hundred thousand. The difference in 

annualized treatment delays shown in 

Table 6 is a reflection of the differing 

responses to prices and alternative 

special controls. The totality of a 

potential ban removes most of the 

variability of response to regulation and 

reduces differences arising from 

different discount rates. 

TABLE 7—COSTS OF A BAN

[In millions] 

Present 

value—3% 

Present 

value—7% 

Annualized 

value—3% 

Annualized 

value—7% 

Total costs assuming durable alternative material .......................................... $33,224.0 $25,867.0 $3,784.2 $2,840.2 

Total costs assuming alternative materials have ten-year replacement life ... 63,953.8 44,714.7 5,359.3 4,909.7 

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38712 Federal Register / Vol. 74, No. 148 / Tuesday, August 4, 2009 / Rules and Regulations 

TABLE 8—POTENTIAL PUBLIC HEALTH EFFECTS OF A BAN

Present 

value—3% 

Present 

value—7% 

Annualized 

value—3% 

Annualized 

value—7% 

Reduced Mercury Exposure ............................................................................ *688.6 *525.5 *57.7 *57.7 

Delayed Caries Treatments (in millions) ......................................................... 27.1 21.0 2.3 2.3 

* Million μg Hg per day. 

J. Regulatory Flexibility Analysis 

The Regulatory Flexibility Act 

requires agencies to analyze regulatory 

options that would minimize any 

significant impact of a rule on small 

entities. Because of the relatively minor 

costs to manufacturing entities 

attributable to this final rule, the agency 

believes that the final rule will not have 

a significant economic impact on a 

substantial number of small 

manufacturing entities. 

FDA records indicate the final rule 

will affect 50 separate products 

manufactured by 16 domestic 

companies. These companies are 

classified in the Dental Equipment and 

Supplies Industry (NAICS 339114) by 

the Census of Manufacturers. The 

affected industry (NAICS 339114; 

Dental Equipment and Supplies) is 

typified by small entities. Only about 35 

of the approximately 875 establishments 

in the entire industry employ more than 

100 workers. According to the Small 

Business Administration Size 

Standards, any entity with fewer than 

500 employees is considered small in 

this industry. We therefore conclude 

that the manufacturing 16 companies 

affected by this final rule will be small 

businesses. The formal costs per 

company, however, are relatively small. 

The annualized costs of developing new 

required and recommended labeling and 

conducting additional assays to ensure 

product quality are not significant for a 

substantial number of small entities. 

The annualized costs per firm, $750 

using a 3-percent discount rate or $865 

using a 7-percent discount rate, are not 

significant. (These annualized costs are 

based on an average of 3.125 products 

per company). The average value of 

shipments for establishments in this 

industry with fewer than five employees 

was $244,100 according the Census of 

Manufacturers. The annualized costs of 

the final rule represent less than 0.5% 

of the annual value of shipments. We 

certify that there will not be a 

significant economic impact on a 

substantial number of small entities. 

VI. Federalism 

FDA has analyzed this final rule in 

accordance with the principles set forth 

in Executive Order 13132. Section 4(a) 

of the Executive order requires agencies 

to ‘‘construe * * * a Federal statute to 

preempt State law only where the 

statute contains an express preemption 

provision or there is some other clear 

evidence that the Congress intended 

preemption of State law, or where the 

exercise of State authority conflicts with 

the exercise of Federal authority under 

the Federal statute.’’ Federal law 

includes an express preemption 

provision that preempts certain state 

requirements ‘‘different from or in 

addition to’’ certain Federal 

requirements applicable to devices. 21 

U.S.C. 360k; Medtronic v. Lohr, 518 U.S. 

470 (1996); Riegel v. Medtronic, 128 S. 

Ct. 999 (2008). 

In this rulemaking, FDA has 

determined that general controls by 

themselves are insufficient to provide 

reasonable assurance of the safety and 

effectiveness of these devices, and that 

there is sufficient information to 

establish special controls to provide 

such assurance. FDA has therefore 

imposed special controls to address the 

risks of exposure to mercury, allergic 

reaction including adverse tissue 

reaction, contamination, mechanical 

failure, corrosion, and improper use. 

These special controls create 

‘‘requirements’’ for specific medical 

devices under 21 U.S.C. 360k, even 

though product sponsors have some 

flexibility in how they meet those 

requirements. Papike v. Tambrands, 

Inc., 107 F.3d 737, 740–42 (9th Cir. 

1997). 

The preemptive effects are the result 

of existing law set forth in the statute as 

interpreted in decisions of the United 

States Supreme Court. FDA therefore 

has not sought separate comment on the 

preemptive effect of this action because 

it is not seeking independently to 

preempt state law beyond the effects of 

21 U.S.C. 360k or existing case law. 

VII. The Paperwork Reduction Act of 

1995 

This final rule refers to previously 

approved collections of information 

found in FDA regulations. These 

collections of information are subject to 

review by the Office of Management and 

Budget (OMB) under the Paperwork 

Reduction Act of 1995 (44 U.S.C. 3501– 

3520). The collections of information in 

21 CFR part 801 have been approved 

under control number 0910–0485; the 

collections of information in 21 CFR 

part 807 subpart E have been approved 

under OMB control number 0910–0120; 

the collections of information in 21 CFR 

part 50 have been approved under OMB 

control number 0910–0130; and the 

collections of information in 21 CFR 820 

have been approved under OMB control 

number 0910–0073. 

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Dental Practice—Dental Services,’’ 2006. 

85. U.S. Agency for Toxic Substances and 

Disease Registry, ‘‘ToxFAQs for 

Mercury,’’ U.S. Department of Health 

and Human Services, April 1999. 

86. Ventura, S.J. et al.; Estimated Pregnancy 

Rates by Outcome for the United States, 

1990–2004; National Vital Statistics 

Reports; April 14, 2008; 56:15:1–28. 

87. American Academy of Pediatrics; 

Breastfeeding and the Use of Human 

Milk; Pediatrics 2005; 115; 496–506. 

88. Eastern Research Group; ‘‘Preliminary 

Estimates: Labeling and Related Testing 

Costs for Medical Glove Manufacturers,’’ 

Memorandum, January 18, 1999. 

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283–290, 2004. 

List of Subjects in 21 CFR Part 872 

Medical devices. 

■ Therefore, under the Federal Food, 

Drug, and Cosmetic Act and under 

authority delegated to the Commissioner 

of Food and Drugs, 21 CFR part 872 is 

amended as follows: 

PART 872—DENTAL DEVICES 

■ 1. The authority citation for 21 CFR 

part 872 continues to read as follows: 

Authority: 21 U.S.C. 351, 360, 360c, 360e, 

360j, 371. 

§ 872.3050 [Removed] 

■ 2. Remove § 872.3050. 

■ 3. Add § 872.3070 to subpart D to read 

as follows: 

§ 872.3070 Dental amalgam, mercury, and 

amalgam alloy. 

(a) Identification. Dental amalgam is a 

device that consists of a combination of 

elemental mercury, supplied as a liquid 

in bulk, sachet, or predosed capsule 

form, and amalgam alloy composed 

primarily of silver, tin, and copper, 

supplied as a powder in bulk, tablet, or 

predosed capsule form, for the direct 

filling of carious lesions or structural 

defects in teeth. This device also 

includes the individual component 

devices, mercury and amalgam alloy, 

when intended to be combined with 

each other to form dental amalgam. 

(b) Classification. Class II (special 

controls). The special control for this 

device is FDA’s ‘‘Class II Special 

Controls Guidance Document: Dental 

Amalgam, Mercury, and Amalgam 

Alloy.’’ See § 872.1(e) for the availability 

of this guidance document. 

Dated: July 28, 2009. 

Jeffrey Shuren, 

Associate Commissioner for Policy and 

Planning. 

[FR Doc. E9–18447 Filed 7–29–09; 4:15 pm] 

BILLING CODE P 

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