IAOMT rebuttal to the ADA misrepresentations of the FDA hearing on amalgam

iaomt

In December 2010 the FDA convened a dental products panel hearing on the safety of dental amalgam. Since that time, Dr. Raymond F. Gist, president of the American Dental Association (ADA) has continually misrepresented the results of these hearings to the public and its membership. Luckily the current availability of the hearing transcripts has allowed the IAOMT the opportunity to correct any misconceptions that may arise from Dr. Gist’s statements.

July 15, 2011

Dr. Michael Adjodha, [email protected]

Dr. Jeffrey Shuren, [email protected]

Dr. Anthony Watson, [email protected]

Re: December 14-15, 2010, hearings pertaining to the classification of dental amalgam fillings

Dear FDA Representatives:

As you know, Robert Reeves, Esq. and I are the authors of two of the four Petitions that were submitted concerning the August 4, 2009, FDA Final Rule classifying dental amalgam fillings in Class II.  Public hearings were held before a Scientific Advisory Committee (hereinafter, the “Committee”) on December 14-15, 2010.

Since that time, the American Dental Association has misrepresented the results of these hearings to the public and its membership.  Dr. Raymond F. Gist, president of the ADA, “commended an advisory panel’s call for continued research while offering support for the Food and Drug Administration’s current amalgam regulation.  The panel found that FDA acted appropriately in ruling last year that dental amalgam is a safe and effective treatment option for the general population.”  These statements appeared in an article published in the ADA News.  We are copying Dr. Gist on this letter in the event he wishes to respond to these comments.

As an attendee at these hearings, I was astonished and disappointed at the ADA’s willingness to misrepresent this record.  The current availability of the hearing transcripts allows me an opportunity to correct any misconceptions that may arise from Dr. Gist’s statements.  Unfortunately, these comments are but another chapter in the ADA’s long history of misleading the public about this restorative material.

I have carefully reviewed the transcript to determine whether support exists for Dr. Gist’s comments.  I am sure you will agree there is not. Discussed below is my summary of the comments that were made by the panelists and the consensus position of the Committee developed in response to the questions posed by FDA.

FDA sought input from the Committee on three sets of scientific questions. The first set of questions concerned the level of exposure to mercury that amalgam bearers receive from dental amalgams. The second set concerned how the reference exposure level for elemental mercury should be determined.  The third set concerned how to weigh risk assessment information and clinical information in FDA’s assessment of the safety of amalgam.  

The first question asked the Committee to…

{slide=Assess the strengths and weaknesses of the data supporting exposure assessments}

“Assess the strengths and weaknesses of the data supporting the exposure assessments from HHS and WHO reports.”  

FDA noted that HHS and WHO both reported that the absorbed dose is between 1 and 22 micrograms per day.  The Committee had concerns about a variety of issues that had not yet been investigated in connection with the mercury dose associated with dental amalgam.  Chairperson Dr. Jeffcoat summarized the comments, as follows:  “Okay. So we do not have a number but we have sort of a strategy to go forward to get a series of numbers for different populations, okay.”  [436]  In other words, the Committee was not content with existing estimates of exposure but wanted further investigation.  

FDA next asked the Committee

{/slide}
{slide=How do age-related parameters factor into FDA’s analysis}

“How…the following age-related parameters factor into FDA’s analysis:

(a) inhalation physiology parameters;

(b) body weight or body mass;

(c) number of amalgam surfaces and filling size; and

(d) are there any other specific age-related physiologic, genetic, pharmacokinetic differences of mercury vapor exposure that should be considered in the risk assessment?”

 Dr. Judith Zelikoff commented that “inhalation physiology parameters between children and adults are like comparing apples and oranges.”  [439] She stated that “these differences really could make a difference in terms of the vulnerability to toxic insult with mercury….” Id.  

Dr. Norman Tinanoff commented that “I don’t think we can extrapolate from adults to children, and especially to infants because there’s quite — as we just heard about the lung capacity and differences of physiology with regard to the lungs, the differences with regard to blood/brain barrier and not many other factors. So in my opinion we just don’t know and we can’t extrapolate until we get real data for children under age 6.”  [441]

In response to questions concerning the stratification of mercury exposures derived from dental amalgam, Dr. Goering of FDA admitted that such stratification had not occurred “per Dr. Richardson,” and that this was something FDA would “take a look at.”  [434-35]  

Chairperson Jeffcoat concluded that “we do not have individual guidelines at this point, and FDA has not stratified the exposures that Richardson reported, which were basically based on averages…”  [437]  

Dr. Burbacher complained that “we just don’t know anything at this point [about fetal exposure.]”  [443]  

Dr. Kotagal confirmed the complaint of the Petitioners that no effort had been made by FDA to express exposure on the basis of milligrams per kilogram of body weight.  [444]  

Dr. Zelikoff confirmed that “the FDA would be remiss in not looking into whether there is any long-term delayed effects in terms of disease manifestation from prenatal exposure.”  [448]  

The Committee concluded that

“exposures needed to be determined for different groups, including children.”[437]

The next issue presented to the Committee concerned

{/slide}
{slide=Urinary levels as an appropriate biomarker for assessing risk and issues of bioaccumulation}

(a) whether urinary levels are an appropriate biomarker for assessing risk of exposure to mercury from dental amalgam. And part

(b), how would the Committee recommend that FDA incorporate issues of bioaccumulation and clearances in assessing risk of exposure to mercury from dental amalgam?  [458]  

Dr. Bates thought that other biomarkers should not be excluded.  [459]  

Dr. Kotagal agreed, suggesting several alternatives [461], and Dr. Zelikoff concurred with them, suggesting observations of cord blood.  [463-64]  

Dr. Ismael stated that, “urinary mercury levels are useful for certain effects for certain type of mercury, but for others you need to look beyond the urine and look at other markers.”  [470]

Dr. Aschner doubted that “urinary levels in the mother can be extrapolated to exposure in the fetus.”  [470]  The Committee consensus was that “urinary mercury levels are the best we have for measuring exposure but we do need to subset out groups of children: fetuses in utero; children from 0 to 3; 3 to 6; and 6 to puberty.  [475-76]

Again, the Committee rejected the FDA’s analysis on estimating exposure.

The Committee was next asked, 

“How would the Panel recommend the FDA incorporate the issues of bioaccumulation which is where some people went in the last question, and clearance in assessing mercury exposure from dental amalgams?”  

The Committee consensus was that there was insufficient information to answer this question.  [489]

{/slide}

{slide=Criticisms of the EPA’s Reference Concentration}

{jwplayer}http://www.youtube.com/watch?v=-L-v9nujPbQ&width=300&height=260&plugins=viral,tweetit&dock=true&viral.onpause=false&playlist=none{/jwplayer}


Attorney Jim Love of the IAOMT

Jim Love of the IAOMT explains why the Fawer Study is not Appropriate for RfC or MRL Derivation in the FDA’s 2009 amalgam rule.

In its Final Rule on amalgam in 2009, the FDA relied on a 1995 EPA risk assessment for mercury, which relied principally on a study by Fawer, et al., in establishing a reference concentration of 0.3 µgs/m?. EPA’s reliance on Fawer was criticized by the Petitioners because Fawer studied workers at a chlor-alkali plant.

Dr. Richardson criticized EPA’s reliance on Fawer, et al., on the basis that the presence of chlorine gas reacted with mercury vapor. The resulting mercuric-chloride did not absorb as well as mercury vapor and did not have the same pharmacokinetics. FDA asked its Committee whether the exposure-response relationship for mercury vapor was modified by concomitant exposure to both mercury vapor and chlorine gas.

Dr. Griffin of the EPA argued that the issue wasn’t worthy of consideration because 250 subjects were considered in the course of three studies, not one, and only 12 of the 250 workers were chlor-alkali workers. The balance of the subjects were dentists and fluorescent lamp workers who were not exposed to chlorine gas.

Dr. Richardson, who had already spoken to the Committee, was not allowed to address this comment, but he later communicated his objection to Michael Adjodha of the FDA.

Dr. Richardson’s comments are set forth below:

mark-richardson-01I was not given the opportunity to challenge the panelist from EPA, nor rebut the claim that my (and co-authors) concern for confounding by chlorine gas exposure in chloralkali workers was a “red herring”. Her claim of “only 12” chloralkali workers in the Fawer, et al study is correct, but this was 12 of only 26 workers studied, or 46% of the exposed cohort. This is not an insignificant proportion of those studied.

Percentage of chloralkali workers in Fawer et al.

Dr. Richardson further noted:

EPA’s IRIS summary reflects EPA’s reliance on studies by Piikivi and Tolonen (1989; 41 chloralkali workers) and Piikivi and Hanninen (1989; 60 chloralkali workers), and Piikivi (1989; 41 chloralkali workers). The studies of Ngim, et al. in 98 dentists, and Liang, et al. in 88 fluorescent lamp factory workers were referenced as “corroborative studies” only, which “bracketed” the exposures within the other studies.

Number of chloralkali workers in studies EPA relies on for Reference Concentration (Rfc)


Dr. Richardson concluded:

Assuming that Ngim, et al. and Liang, et al. cohorts are added into the total studied cohorts, the total persons exposed = 354, of which 154 (43.5%) are from chloralkali plants. Again, this is not an insignificant proportion, nor is concern for confounding by chlorine gas exposure a “red herring”.

Further, if Ngim, et al. and Liang, et al. are only corroborative studies (noted in the IRIS summary as “bracketing” the exposure range of the other studies), then they don’t count in the total, and the total exposed considered for RfC development was 168, of which 154 (91.7%) exposed workers were chloralkali workers.

Percentage of chloralkali workers in all studies.

Of all of the reported average Hg levels in air for the various exposed groups, the Ngim, et al. study reported the lowest time weighted average air concentration (the lowest LOAEL; 14 µgs /m3) associated with effects, of any of the studies.

So, it appears that the most sensitive study (effects at lowest level) was ignored; it may also indicate that co-exposure to chlorine gas increased the LOAEL (decreased sensitivity in workers) by 85% (raising the LOAEL from 14 to 26 ug/ m3); again, no red herring.


Therefore:

– reliance on Fawer, et al. has 46% of exposed persons from chloralkali industry;

– reliance on all studies has 43.5% chloralkali workers;

– if Ngim, et al. and Liang, et al. are “corroborative” only (i.e., used for comparison but not for direct calculation of REL), then 91.7% of exposed group were chloralkali workers.

– reliance on Fawer, et al. and others as per USEPA also ignored the lowest measured LOAEL.

In preparing his 2009 risk assessment for mercury, Dr. Richardson relied on Ngim, et al., which did not rely on the study of workers from the chloralkali industry. The paper also represented the lowest reported LOAEL. Dr. Griffin stated that the goal of REL development was to identify the study that had critical effects at the lowest level; and that basing the RfC on this ‘most sensitive study’ helps protect against effects observed at higher levels.

So, Dr. Richardson’s concern for use of chloralkali workers was not a red herring. In fact, the Ngim, et al. study reported the lowest LOAEL of the studies relied on by EPA, and has no confounding interference by concomitant chlorine gas exposure. Neither Dr. Griffin nor FDA has since commented on Dr. Richardson’s criticisms. As we stated in our Petition, reliance on Fawer, et al. is misplaced.

Dr. Ismail supported the view of the Petitioners that the literature needed to be updated between 1992 and 2010, and that it was inappropriate to rely on a 1995 EPA RfC while ignoring the many years of published research during this period. [494] Dr. Bates agreed with Dr. Ismail. [495]

The Committee was next asked to discuss the

{/slide}
{slide=Strengths and weaknesses of the EPA reference concentration} Strengths and weaknesses of the EPA reference concentration with respect to the general population and sensitive subpopulations.[501]

Dr. Dourson noted that “Homework Assignment” invited speakers Drs. Farland and Ginsberg criticized the EPA RfC uncertainty factor of “3” for human variability.  Dr. Griffin explained that a default of “10” was typically applied if there were no reproductive or developmental studies.  [503]  She also commented that the reproductive studies were “a bit iffy” at the time the RfC was announced in 1995.  Id.  She said newer studies do address reproductive and developmental effects.  Given an opportunity to defend the decision to apply an uncertainty factor of “3”, Dr. Griffin declined, encouraging FDA to reach its own conclusions.  Significantly, Dr. Richardson applied an uncertainty factor of “10” in his recent risk assessment for mercury (presented to FDA in connection with these hearings.  Richardson rejected the EPA’s use of a “3” for a safety factor, claiming, “[u]ntil further data are available on developmental and neurological outcomes associated with Hg° exposure in humans, it is essential that precaution be applied in the determination of updated and revised reference exposure levels for the protection of public health.”  California EPA was so unconvinced by the available data that it provided additional precaution to protect the “greater susceptibility of children and their developing nervous systems.”  CalEPA added an additional factor of “10” for a total uncertainty factor of “300.”

Certainly appropriate is Dr. Griffin’s concern about the “iffy” justification for the use of an uncertainty factor of “3.”  [503-04]  In an attempt to determine what studies EPA relied on in applying an uncertainty factor of “3,” the undersigned contacted the EPA hotline and inquired.  In its responsive email, EPA represented that “it appears that a UF of 3 for reproductive effects database deficiencies was customary.”  (See email thread, Exhibit 1.) Later that day, EPA provided a new basis for the UF, claiming that four studies formed the basis of the EPA’s decision.  The Steffek, et al., study rat fetuses exhibited cranial defects in the medium and high exposure groups.  In Mishinova, et al., rates of pregnancy and labor complications were high among women exposed to mercury, and the effects depended on “the length of service and concentration of mercury vapors.”  Lauwerys, et al., addressed the fertility of male workers exposed to mercury vapor and found no statistically significant changes in the children born to the exposed group.  Finally, Baranski, et al. reported that female rats exposed via inhalation to mercury vapor at an average of 2.5 mg/mᵌ for six hours / day, five days / week for 21 days experienced longer estrus cycles than unexposed animals, and longer than normal estrus cycles in the same rats during the period of exposure.  These studies could not possibly provide a significant degree of confidence for EPA or FDA that dental amalgams present no risk of developmental or reproductive harm.  It is little wonder that CalEPA and Dr. Richardson refused to follow EPA’s lead and apply an uncertainty factor of “3.”  Dr. Griffin’s position that sufficient data exists to justify an uncertainty factor of “3” is certainly undercut by one of FDA’s questions to the Committee, which admits that, “[v]ery limited to no clinical information is available regarding long-term health outcomes in pregnant women and their developing fetuses, and children under 6, including infants who are breastfed.”  [558]

The Committee consensus was that reliance on the 1995 EPA RfC should be rejected.

We are suggesting that the methods from the newer studies and the data from the newer studies be reviewed in order to determine RfCs, because the question had to do with RfCs. Use an uncertainty factor when we do not have data for sensitive populations, because you have no choice, frankly. And when you do have data for sensitive populations use a model similar to the kind of models that we talked about for the RELs to get an RfC for the sensitive populations. And if it’s available, analyze genomic information, such as we have it.  [510]

Dr. Dourson further summarized the expectations of the Committee:

So what I would like to enjoin, and you’ve already heard — everyone is doing this, is to ask our FDA scientists, who are really very good at this, to look at these new data, the data since 1995, and really kind of develop your own reference concentration. If the critical effect is neurological, so be it. If we can use a human NOAEL from these children’s studies, that would be great, but Dr. Aschner and Dr. Bates are talking about making sure that that’s sufficient length of exposure. You may need an uncertainty factor there.  [513]

Dr. Fleming further confirmed that the Committee was not endorsing the EPA RfC.  [518]  

Thus, contrary to the unfounded contentions of the ADA, the Committee was not endorsing reliance on the outdated EPA RfC, but rejecting this reliance and encouraging FDA to prepare its own risk assessment.

{/slide}

{slide=The Committee next addressed available clinical studies}

In FDA’s final rule, FDA stated that human clinical studies of dental amalgam bearers have not established a causal link between dental amalgam and adverse health effects in adults and children age 6 and older. This conclusion relied on many human clinical studies reviewed in the FDA White Paper, Addendum and final rule. FDA stated in its rule that human clinical data for children under the age of 6 and pregnant women, including exposures to the fetus, is limited. The petitioners dispute the methodology, conclusions, and FDA’s interpretation of these studies.

So the two questions in this section are — or comments for discussion are: Assess the strengths and the weaknesses of the clinical studies on dental amalgam, including whether appropriate endpoints were evaluated. Number 2: Do the clinical studies support a relationship between exposure to mercury vapor released from dental amalgam and adverse health effects associated with renal, immunological, allergic, neurobehavioral or psychological function? Are there other adverse health events identified by these clinical studies?  [519-520]

Dr. Kotagal reviewed the neuropsychiatric tests that were utilized in the Casa Pia studies and concluded that he “really feel that we don’t have any adequate neuropsychological information in preadolescent children there that we can rely on.”  [522]  Dr. Rue stated that, “I feel that the safety issue from everything we’ve heard in the last 2 days still is in question. And especially when there are quite a few alternatives available.”  [523]  Dr. Fleming confirmed his concern about amalgam’s risks.  “I — you know, my concern is the risk. And I’m not even sure that what we’re doing is a risk-benefit analysis. I think risk is a stand-alone issue, aside from benefits and effectiveness. So I do echo that concern that we focus on that part of it.”  Dr. Bates believed that further research was necessary.  “I think it’s also important to call for — you know, identify specifically particular endpoints and call for further studies to be done. And I would in that regard particularly like to mention the neurodegenerative diseases, MS, Alzheimer’s and Parkinson’s…. I can say that the data on these three outcomes are very inadequate and really one couldn’t make any judgment whatsoever. And so I think it would be appropriate for this committee recommend that more studies be done. And I think actually that it goes to the FDA position. They have mentioned that there’s a paucity of such studies but it wouldn’t hurt for this committee to actually reinforce that, so maybe independent investigators out there will perhaps carry out some such studies.”  [525]  The paucity of data demonstrating safety led Dr. Ismael to also call for more studies.  “I suggest an independent body, which is the AHRQ, the Agency for Healthcare Research and Quality, evidence practice centers — I think there are now 15 or 13 of them — to do a systematic review on the safety of amalgam using clinical studies — of course, that’s what they do; they don’t look at animal studies; they just look at clinical studies — using the standards of evidence that’s used in systematic reviews to come with a summary and maybe a meta-analysis of all the data to reach a conclusion on — to answer the question, is amalgam safe in different population groups, in different ages, in males or females, different, maybe, sensitivities or susceptible populations, if there are data on those.”  [528]  Dr. Bates seemed particularly concerned about the demonstrated relationship between amalgam fillings and hearing loss.  “[W]hen you look at this graph here, it is — the horizontal axis is number of amalgam fillings and threshold of hearing and it does appear with a number of amalgam fillings based on these data that there is progressive hearing loss and there’s no evidence, obvious evidence, there of any sort of threshold.”  [534]  

Dr. Aschner expressed concern about the Casa Pia studies’ failure to follow the subject children for a sufficient period of time.  “So you know, if you look at kids when they’re 6 or 7, it’s not going to tell you anything about — look at a certain neurotransmitter, for example, dopamine, they might lose 30 or 50% of the content of dopamine in their brain and if you do any behavioral test, they’ll be completely normal. It won’t be until they lost 80 or 90% of these cells and even if they’re on a trajectory for a normal decline in the number of these cells, these effects would [sic] be apparent at a much earlier age. [538]  

Dr. Zelikoff expressed concern about allergy and hypersensitivity to mercury, and argued that it is much more prevalent than some may think.  “Since we are talking about Number 2, as well, I clearly have strong comments about that. I think that there are a number — I’ve heard it by some speakers, I’ve heard it by FDA, I’ve heard it from some Panel members, in terms of the low risk of — excuse me — metal sensitivity, in terms of allergic reaction; it’s an allergic — hypersensitivity responses. And it’s not so low. I mean, I’ve heard it called extremely rare. I don’t know how you define extremely rare, but in searching the literature, I found anything from 2% to 5% of the North American population….  But I don’t think having a 2 or 5% allergy is low for the North American population.”  [540]  “I think, in terms of autoimmunity, that’s something that there is more information on. It’s also considering quality of life, as we’ve just heard from another panelist. That’s something that has to be considered. Autoimmunity is not something, lupus is not something, scleroderma is not something you can take very lightly. It can destroy quality of life dramatically, so I think we need to look into that.”  [541]  “Changes in the immune response is going to lead to possibly increased incidents of bacterial infections, viral infections, et cetera, but is that an obvious effect right now or is it a subclinical change, so I think that’s — you know, I don’t think immune suppression could be a point of departure because you’re not seeing it right then and there, but as far as autoimmunity, I think the FDA needs to do a lot more work in terms of looking into that and I think it could be a very important endpoint that needs to be evaluated better.”  [542]  Dr. Kotagal continued, “You know, there’s exposure and there’s a long latent period before one becomes clinically symptomatic. So really, there is a synaptic redundancy in the system. We can lose a bunch of synapses but not really have function affected and for example, you know, senile clogs develop in our brain starting around 25, 26 years of age.  Mild cognitive impairment doesn’t occurs [sic] until the fifties or sixties and maybe a decade later, so there is really a period where there is silently things are going wrong, but we are just not aware.”  [545]

In summarizing the discussion, Mr. Anthony Watson of FDA stated, “I guess what I wanted to point out was I heard that there is still more work that needs to be done and that there were some flaws in the information that’s there.”  Dr. Goering emphasized that the data was sometimes conflicting.  He noted that the Echevarria studies “did identify neurobehavioral effects at levels of urinary mercury that were very low.  However, there are other studies of dental personnel with much higher urinary mercury where they did not observe neurobehavioral effects.”   [551]  Dr. Zelikoff confirmed that this was typical for exposures to metals.  “[I]t’s very common to have effects at low levels of metals and have different effects in the medium and sometimes no effects at high levels.”

Dr. Kotagal noted that the quality of conflicting Alzheimer’s Disease studies was evaluated by Mutter, et al., in which 1,041 references were reviewed.  [554]  Mutter concluded that the weight of the evidence demonstrated a causal relationship between mercury exposure and this disease.  

In stating the consensus of the Committee, Dr. Zelikoff emphasized that important endpoints were ignored in the clinical studies.  Chairperson Marjorie Jeffcoat agreed.  [556]{/slide}

{slide=Data concerning pregnant women, developing fetuses, breastfed infants and those under 6}

The Committee was next asked whether FDA appropriately represented the strengths and weaknesses of the available data in discussing information concerning pregnant women and their developing fetuses and children under six, including infants who are breastfed.  [558]

Consumer representative Karen Rue found that that it is imperative to consider what we don’t know about this issue, and to emphasize that we need to consider the health of the unborn and the health of those children forty years from now.  [559]

Dr. Tinanoff emphasized that warnings should emphasize that certain populations may be more sensitive to mercury than others.  Id.  Karen Rue emphasized that warnings should emphasize what we don’t know about amalgam safety.  Id.  Dr. White emphasized that dental amalgams are not safe for everyone.  

What’s not said is it’s not safe for use by everyone. We’d all agree with that, it’s not safe for use by everyone. Regarding pregnant and nursing women, dentists should consider not placing them. Because of the unknown risks, dentists should consider not placing in pregnant and nursing women. Dentists should consider not placing in patients with neurologic or kidney impairment or function. Avoid placing in patients who have allergic or hypersensitivity to mercury.  [566]

Dr. Fleming reminded Dr. White that if amalgams were not to be used in pregnant women, then a contraindication (as opposed to information for use) would be appropriate.  Dr. Fleming’s biggest concern was justifying safety in the face of no clinical evidence.  [567]  However, FDA’s Anthony Watson pointed out that regulations require contraindications to be supported by data.  Id.  Dr. Aschner expressed confusion about Mr. Watson’s comments, stating, “I’m disturbed by statements such as in the presence of data, the FDA can use a contraindication; but in the absence of data, we can assume that something is safe. It just doesn’t jive for me.”  [570]  

Of course, Dr. Aschner’s confusion arises from his lack of understanding about the regulatory scheme.  Any discussion of contraindications can only begin after FDA previously confirms there is adequate evidence of safety for the general population.  FDA regulations clearly require adequate data demonstrating safety and effectiveness even before a device may be regulated in Class I or Class II.  [See, e.g., 42 FR 46030, 13 Sep 1977]  As the repeated comments of the Panelists remind us, these data simply do not exist.  The discussion of contraindications arises only after safety for the general population has been demonstrated.  Because general evidence of safety has not been demonstrated, the discussion of contraindications was confusing.  

Dr. Ismael reminded FDA that, “there are some case studies documenting some detrimental effects of amalgam restorations in some patients who may be sensitive to mercury.”  He further noted that there “is [a] lack of data on children less than 6 years of age….”  He encouraged FDA to “make a clear statement that there are no data for that.”  [569]  

Dr. Burbacher refused to “wordsmith” a warning for FDA.  He reminded the Committee that the question was “whether the FDA appropriately represented the strengths and weaknesses of the available clinical data.”  He concluded that FDA had not.  [578]

{/slide}

{slide=Risk Assessment, Clinical Studies and FDA’s Regulatory Approach to Dental Amalgam}

The Committee was next asked to discuss “how FDA should weigh risk assessment and clinical studies in considering its regulatory approach to dental amalgam.”  [583]  

Dr. White asserted that the consensus was to use the available clinical studies to redo the risk assessment.”  Id.  

Dr. Kotagal flatly refused to consider amalgam use in children.

I may be overstating the case, but I think that children are different from adults and I think children need to be — infants and children need to be addressed separately than the adults because of their increased risk. And I think that there really is perhaps no place for mercury in children.{587}

Dr. Bates stated, “In regard to the FDA question about weighing risk assessment and clinical studies, my perspective on this is very simply that you define all the clinical studies’ information and then you use a risk assessment or a modeling approach to extrapolate from there.”  [588]  

Dr. Zelikoff believed that “weight of evidence should not just consider certain studies but all scientifically sound studies that will add to or detract from the weight of evidence.”  [590]  

On the subject of risk-benefit, Dr. Aschner commented, “I think the important issue again is risk/benefit and I would question whether a 10-percent benefit, with all the uncertainties that we don’t have information about, is worthy of consideration.”  

Dr. Fleming offered his opinion that there are not enough data to support the notion of safety. I think, to be quite frank with the Panel, I’ve been in clinical practice over 30 years and have not used amalgam in 25 and I find this product to be not necessary in the clinical practice of dentistry. I am confounded by the fact that safety is — or the use of the product is allowed in a population where there aren’t — there isn’t enough data to support safety. It absolutely confounds me.[591]  

Dr. Ismael agreed and stated, “we have to find ways to recognize that there are some patients who cannot — should not have amalgam.”  [592]  He further stated that, “And children less than 6 years of age, I would restrict it significantly and have the — be clear that the data do not — while the efficacy may be there in terms of the clinical practice, but that issues about safety, and so on, have not been documented very well.”[593]

Dr. Thompson stated, “I have serious concerns about this and think that really we have to look at informed consent; definitely not in pregnant women and definitely not in those below 6 years of age.”  Id.  Ms. De Luca agreed.  “For some populations, I don’t think amalgam should ever be used.”  Ms. Rue said that she was “very thankful for the discussions of safety and the patient awareness and education because that’s what I feel the focus needs to be.”  Concerned about long-term health outcomes, Dr. Bui proposed that patient registries be established for patients in whom amalgam was placed.  “That would provide significant data to study long-term outcomes.”  [595]  

Dr. Dmytryk emphasized that, “We need to look at [mothers, infants and children separately.”  He further stated that, “the small subset of the population that really seems to be highly susceptible, we really need to focus on them and not treat them the same as the general population.”  [596]

Dr. Burbacher agreed with Dr. Dmytryk.  “I think if you look at the various children’s advocacy groups, children’s groups that are looking at environmental health, as well as the Administration’s program on children’s health, the issue here is to reduce exposure to children.”  Id.  “So why put amalgams in children if we know they’re going to live with that for the rest of their lives? And we don’t know what that’s going to do. So do we have to prove that before we stop doing it, is one question. I don’t think we should.”  [597]  “If we don’t know in the long term that these early exposures are safe, is it better to just go ahead and keep doing it or is it better to say, well, we’ll err on the side of caution and not do it, since we have alternatives?”  [599]

 Dr. Thompson made it clear that amalgam was not necessary.  “So from a benefit point of view, I don’t see it for amalgam at all.  And so it raises the question — where we are with it.  We have members of the Panel who don’t use it.  We certainly don’t only teach it to make sure that people probably can pass the boards at New York University.  We don’t use it at all if at all possible.”  [600]

With all of the discussion centered on limiting amalgam in children under the age of six, Dr. Kotagal, a pediatric neurologist, stated that physiologically, there was no difference between a children aged five and seven.  He believed that prohibitions on amalgam use should be applicable to all children, including prepubescent children.  [602]

Dr. Tinanoff agreed with this statement and advocated no amalgam use in children under the age of twelve.  Dr. Kotagal agreed with this approach.

Dr. Bates confirmed the consensus of the Committee that FDA’s Final Rule and its risk assessment of dental amalgam were rejected.  “I just want to note that it talks here about the ATSDR and the EPA’s established levels of exposure. We are proposing here an FDA level.  So that would need to change, assuming there is some action taken.”  Dr. Bates also doubted the reliability of the FDA’s statement that “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.”  In view of Dr. Richardson’s data, it appeared that “quite a few people could be exposed to levels above those.”  [607]

Dr. Jeffcoat confirmed that, “if the FDA chooses to act on our suggestion, those numbers may — Dr. Richardson’s numbers may be recalculated.”  Id.  

Even the authors of the “homework reports” did not support the FDA position on the risk of dental amalgam.

Dr. Gary Ginsberg proposed an uncertainty factor of 100 to 300, causing him to recommend the revision of the EPA RfC from 0.3 µgs/mᵌ to a range of 0.02 µgs/mᵌ to 0.06 µgs/mᵌ.  As you know, an RfC in this range is supported by a multitude of recently published risk assessments for mercury, including, Richardson (2009), Richardson (2011), Lettmeier (2010), and CalEPA (2008).  As Dr. Richardson pointed out during his presentation at the public hearings, all U.S. amalgam bearers would absorb mercury in quantities exceeding the amount permitted by Dr. Ginsberg’s recommended RfC.  

Dr. William H. Farland also believed that EPA’s uncertainty factor of 30 was too low and advocated a total factor of 100 or 300.  He estimated that the daily absorbed dose of mercury for those with amalgam fillings was 1-7.5 µgs/day.  

Dr. Robert A. Yokel believed that the EPA RfC of 0.3 µgs/mᵌ was protective, but believed that the range of mercury exposure for amalgam bearers was 1-15 µgs/day, thus exposing the vast majority of amalgam bearers to absorbed quantities of mercury that exceed the quantity permitted by the current EPA RfC. {/slide}

{slide=2006 and 2010 FDA Advisory Committee disagree with the FDA}

It is clear from this record that neither the Committee nor the authors of the homework assignments supported the FDA findings and methods reflected in the July 2009 Final Rule.  The ADA’s representations to the contrary are but another chapter in a long-standing scheme to deceive the American public about the dangers posed by this material.  

Nor will the ADA find support from the Advisory Committee that was assembled in 2006.  This Advisory Committee voted 13-7 to reject the proposition that the FDA White Paper demonstrated amalgam safety.  Indeed, the FDA and the ADA appear loathe to accept—or even discuss– the clear findings of these two Committees.

The FDA never mentioned the 2006 Committee’s rejection of the FDA’s White Paper in its 116-page Final Rule or in its concomitantly issued 68-page Addendum to the White Paper.  

In discussing the history of FDA amalgam regulation during the December 2010 hearings, Michael Adjodha stated that the 2006 Committee “asked FDA to revisit the White Paper to conduct a more comprehensive review of the scientific literature regarding the effects of mercury exposure from dental amalgam, including consideration of sensitive subpopulations.”  [21-22]  In fact, the 2006 Committee was asked whether the White Paper “objectively and clearly presented the current state of knowledge about the exposure and health effects related to dental amalgam.”  The Committee voted “no” by a 13-7 margin.

To the question of whether the White Paper’s conclusions were “reasonable,” the panel also voted “no” by the same 13-7 margin.

FDA’s compliance with the 2006 Committee’s recommendations was spotty at best.  On pages 7-9 of the FDA’s Addendum, FDA explained why it would not or could not comply with the Committee’s recommendations.  Instead of developing a record of compliance, FDA developed a record of defiance.  Certainly, the comments of the 2010 Committee confirmed that the FDA Addendum did little or nothing to ameliorate the expressed concerns of the 2006 Committee.  

Significantly, FDA did NOT ask the 2010 Committee whether dental amalgam should be banned, the very relief requested by our Petitions.  Yet Dr. Shuren is obviously aware that banning amalgam is the issue on the table.  At a recent Town Meeting in Irving, Texas, Dr. Shuren was quoted as stating, “the question is whether or not dental amalgams should be banned altogether. Now the panel did not recommend that. They did point out that there may be certain populations who are more sensitive to dental amalgam.”  

As we all know, the panelists were not asked whether a ban or Class III classification was appropriate.  Nor were they instructed on the regulations that dictate when a ban or Class III classification is legally appropriate.  Doing so would have allowed this Committee to address such considerations.  What this Committee did do was repeatedly emphasize that there is an absence of scientific data that would prevent FDA from reaching the conclusion that dental amalgam is safe for all people.     

It is obvious that FDA’s position on dental amalgam has not received support from either of the FDA hand-picked Scientific Advisory Committees empaneled in 2006 or 2010.  It also did not receive support from the “homework assignment” consultants who spoke at the December 2010 public hearings.  

FDA’s position is further belied by recent published risk assessments for mercury, as discussed herein.{/slide}

As detailed in the Petitions filed with FDA, it is our further opinion that FDA has disregarded many of its own regulations in failing to classify dental amalgam in Class III.  

A passage in the New England Journal of Medicine (April 1987), provided that:

Science is a hard taskmaster, and in the light of mounting evidence that suggestions of toxicity are for the most part ultimately confirmed by painstaking scientific inquiry, perhaps it is time to re-examine whether scientific standards of proof of causality – and waiting for the bodies to fall – ought not to give way to more preventive health policies that are satisfied by more realistic conventions and that lead to action sooner.

For the good health of this country’s citizens, we request that you take steps to immediately ban or properly classify this material.

Sincerely yours,

James M. Love
cc:   Robert E. Reeves, Esq.
Matthew Young, President, IAOMT
Jim Dickinson, FDA Webview
Dr. Raymond F. Gist, President, ADA
Dr. Richard Edlich
James Turner, Esq.

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