From: BULLELKMAN@aol.com
Sent: Monday, July 26, 2004 12:55 AM
To: FDADockets@oc.fda.gov; brownchas@erols.com
Cc: sandyduffy@comcast.net; FreKoss@aol.com
Subject: Docket Number #03N-0169

  
Dear FDA,

 

Please post this e-mail to Docket Number # 03N-0169. It is imperative that this important information becomes part of public record on mercury dental fillings. By recording this 

e-mail to Docket Number #03N-0169, it becomes information that will be available to the "public" to include the American public, elected officials and the media because of Freedom of Information Act. 

 

It is critical that the "public" has access to this information.

 

Thank you,

Mary Ann Newell

Manager of the Files for Consumers for Dental Choice

________________________________________________________
      Subject:
     Amalgam Review - meeting etc.
     
      Date:
     2/24/2004 12:43:15 PM Pacific Standard Time
     
      From:
     Fre Koss
     
            Reply To:
            
           
            To:
           falkm@lsro.org
           
            CC:
           Fre Koss
           

           
           

     

 Michael Falk, Ph.D.
Executive Director
LSRO

Re: Scientific Review and Analysis of possible health hazards of mercury amalgam. 

Dear Dr. Falk:

As a follow up to our last conversation wherein you denied our request for the list of peer reviewed studies submitted by LSRO to the scientific advisory committee after the first meeting,  we are once again asking for this literature. Although you informed me that we were not entitled to receive this material prior to the advisory committee's completion of their investigation,  we believe as public citizens who responded to an FDA request for scientific literature,  that we have the right to not only request the data but obtain it. From the information we've been given by the FDA, much of the submitted peer review literature does not seem to have given to the advisory committee.

As I mentioned in our last conversation, members of the committee at the December meeting requested research prior to 1996 or 1997, and you assured them at that time that they would receive same.  There were studies prior to these years submitted to the docket ,yet when we spoke, you said that you would not submit these to the committee, but would only submit a summary of this time period.  How was this summary chosen and organized and who made those decisions, and were any of the  studies submitted to the docket from this time period submitted?   

According to the mandate of the review, we were under the impression that only primary research was mandated  for submission, not summaries.  We would like to receive a list of the data submitted to the docket prior to 1996 as well as studies extrapolated for review by the advisory committee.

With reference to the "background" literature submitted to the advisory committee prior to the first meeting,  more specifically Dr. Clarkson's recent work published in the New England Journal of Medicine , I am forwarding for your perusal Bio-Probe's scientific rebuttal to this paper:

Also, you had mentioned that this advisory committee will make recommendations regarding the classification of dental amalgam, rather than making the final decision as to the classification of encapsulated amalgam. If I am correct, who makes the final decision and what committee reviews their this advisory committee's recommendation? 

Did the February 16th meeting take place, and if so, when will the report be forthcoming? I had thought it was due by February 23rd.

Also, please advise who the federal government employee was at each meeting, and  whether or not they approved of the agenda prior to the meetings? 

Thank you for your consideration, and I look forward to hearing from you.

Respectfully,
Freya Koss
Consumers for Dental Chioce

Bio-Probe Rebuts NEJM Amalgam Article
PRO-AMALGAM ARTICLE IN  NEW ENGLAND J. OF MEDICINE

Is it Gospel, or even accurate, just because it is published in the prestigious New England Journal of Medicine (NEJM)?

Apparently, many think so, but that does not mean that they are correct, or wise. Think of it; If an issue of dental therapy is determined by publication in the NEJM, and they are wrong, then the harm to the practice of dentistry and to the public health could be pronounced.

Such a case may now have occurred by a publication in the October issue of the NEJM [NEJM, 349(19):1731-1737, Oct 2003]. The article is entitled ""The Toxicology of Mercury - Current Exposures and Clinical Manifestations."" The lead author is Thomas W. Clarkson, Ph.D. The other authors are Lazlo Magos, MD and Gary Myers, MD.

Very few people, indeed, will take the time and trouble to examine this paper in terms of accuracy and credibility. Bio-Probe will! We are troubled by several aspects of this article.

1. This is not primary research; it is a Review Article. It is even identified as a ""Review Article"" in the NEJM. This obviously means, virtually by definition, that it represents the views of the authors, which very well may be selective.
In the section on dental amalgam mercury (pages 1732-1733, all of 5 paragraphs), the authors utilized only nine (9) references to conclude: ""Patients who have questions about the potential relation between mercury and degenerative diseases can be assured that the available evidence shows no connection.""
Of the nine references utilized to reach this conclusion, three were background information derived from reference texts. The other six were all studies published in dental journals [J. Dental Research (2), J. American Dental Association, Community Dentistry and Oral Epidemiology, Acta Odontologica Scandinavia.]
These dental journals are probably not even peer reviewed, let alone reviewed by qualified mercury toxicologists. Take a look, for example, at one of their references utilized, by Ahlqwist, et al. in the Acta Odont Scand. This was one of a series of reports that began as a retrospective, epidemiologic ""study."" The number of amalgam surfaces in the subjects were estimated from reading panoramic x-rays. Further, the ""subjects"" in the study all had amalgam fillings; there was no control group without amalgams. The ""study"" groups were divided into a group with 4 or less amalgam surfaces compared to a group with 20 or more amalgam surfaces. This study has no validity, even by the quite divergent standards of epidemiology!
* Why then, did Clarkson and associates arrive at their conclusion utilizing only studies from dental journals?
* Why did Clarkson and associates totally ignore the many studies published in validly peer reviewed medical scientific journals?
* Why did Clarkson and associates base their conclusions, at least partially, on studies that were clearly invalid scientifically?*******

2. Clarkson and associates base their conclusion of no harm from amalgam mercury on levels of mercury found in urine. It has been known, and well determined scientifically, that measurements of mercury in urine are NOT a valid indicator of body burden or toxic effects. A full monologue could be utilized to scientifically validate this. We will point out just a few.
* ""In conclusion, the evidence to date indicates that a substantial amount of dental amalgam Hg vaporizes into mouth air, the Hg vapor is inhaled and swallowed, and significant concentrations of this Hg are distributed in body tissues resulting in alteration of cell function. Blood and urine Hg levels remain relatively low during amalgam Hg exposure, and therefore may be poor diagnostic indicators of the very high Hg levels that accumulate in some body tissues as a consequence of such exposure. The foregoing experimental findings are in marked contrast to opinions recently pronounced by spokesmen for the dental profession."" [Toxicity Assessment of Mercury Vapor from Dental Amalgams. Goering, PL; et al (including Thomas W. Clarkson), Fundamental and Applied Toxicology, Pg. 323, 19:319-29, 1992]
* ""In view of the present knowledge about mechanisms responsible for mercury concentration in the blood and urine, a close correlation between them and the concentration in any critical organ should not be expected. Thus, in an individual case neither urine nor blood may indicate the degree of risk of intoxication."" [Maximum Allowable Concentrations (MAC) of Mercury Compounds: Report of an International Committee (including Thomas W. Clarkson and Lazlo Magos). Arch Environ Health, 19:891-905, pg. 894 Dec 1969] 
* ""The distribution of mercury into body tissues is highly variable and there appears to be little correlation between levels in urine, blood or hair, and toxic effects."" [Pg. 470, Workshop: Biocompatibility of Metals in Dentistry, NIDR, J American Dent. Assoc., 109:469-71, Sep 1984]
* ""There are at present no suitable indicator media that will reflect concentrations of inorganic mercury in the critical organs, the brain or kidney, under different exposure situations. One important consequence is that concentrations of mercury in urine or blood may be low quite soon after exposure has ceased, despite the fact that concentrations in the critical organs may still be high."" [Environmental Health Criteria 118: Inorganic Mercury, World Health Organization, Pg. 61, Geneva, 1991]
There are a great many more of these references, some including Clarkson and Magos, but this is enough to ask -
* Why did Clarkson and associates arrive at an important conclusion based on an indicator they knew to be invalid?
* Why did Clarkson and associates ignore validly published science, including their own?*******3. Even worse, Clarkson and associates state: ""However, urinary concentrations in people with amalgams (about 2 to 4 ug of mercury per liter) are well below concentrations found in people who are occupationally exposed to mercury (20 to 50 ug of mercury per liter) unless they are also excessive chewers."" (Pg. 1733) This statement is shocking, incredible and irresponsible!
Occupational standards for mercury exposure are limited to 40 hours per week, in otherwise healthy adult (usually) males. It says so in the documents establishing occupational mercury exposure standards. These documents also require that the workers be clearly informed of the mercury exposure, and be medically monitored.
We have been involved in dentistry for 45 years. Never once have we seen a patient who inserts the mercury fillings at 9:00 am and removes them at 5:00 pm, Monday through Friday. Further, we have seen many children, pregnant women, and otherwise ill adults with mercury fillings. These opinions issued by Clarkson and associates are the type that would be expected from individuals attempting to justify a predetermined position, certainly not from objective scientists who have carefully evaluated all of the scientific literature before publishing something that could ultimately be detrimental to humanity.
What are harmless levels of human exposure to mercury vapor? Check the following references, all of whom are from expert mercury toxicology groups, and all of whom state that a ""harmless"" level of human exposure to mercury vapor has never been found! 

* ""There is no known readily determinable biochemical measurement whose deviation from normal regularly precedes development of toxic effects."" (Page 901) and; ""When numerical values for MAC values are considered, it is obvious that there exist little epidemiological data which provide scientifically satisfactory information about detailed dose-response relationships in man, even for a single mercury compound."" (Page 902)[Ibid: MAC Committee, 1969 (again including Thomas W. Clarkson and Lazlo Magos)]
* ""Because of the prevalence in the general population of nonspecific signs and symptoms which can be associated with mercury, it is difficult, if not impossible, to establish a level at which no effects are observed."" [Criteria For a Recommended Standard: Occupational Exposure to Inorganic Mercury. National Institute for Occupational Safety & Health, NTIS NO. PB-222 223, page 79, 1973]
* ""The dose-response relationship depicted in Figure 6-5 does not exhibit any clear threshold.""[Mercury Health Effects Update: Health Issue Assessment. U. S. Environmental Protection Agency, EPA-600/8-84-019F, page 6-12, 1984]
* ""A no-observed-adverse-effect level (NOAEL) could not be determined from these animal studies. The lowest-observed-adverse-effect level (LOAEL) was found in the subcutaneous exposure study by Druet et al (1978). Using this animal LOAEL (0.05 mg/kg), equivalent human oral and inhalation LOAEL values for kidney effects can be determined."" (Pg. 113) [Ibid. W.H.O., 1991] [BP Note: A NOAEL is fundamentally the same as a ""toxic threshold."" That is, an exposure level below which no harm occurs. So, W.H.O. states that no harmless level of mercury exposure has been scientifically determined. Mercury exposure standards are based on LOAELS, not NOAELS.] Clearly, responsible and qualified mercury toxicology scientists admit that no level of human exposure can be considered harmless. Doctors Clarkson and Magos have even been included in some of these evaluations. They should know better!
* Why do Clarkson and associates admit that the largest non-occupational exposure to mercury in the general population is from amalgam dental fillings, then blithely state that the exposure is harmless without providing a valid scientific foundation?*******
Perhaps the NEJM should take note of the events around the world to limit, and eventually stop, the use of mercury amalgam dental fillings. Many countries have issued official advisories against the use of amalgam in various circumstances: Canada, France, Finland, Germany, Norway, Sweden, and The United Kingdom. Sweden and Norway have already officially limited its use. Sweden has directed that a program be developed by June 2004 that would ban the use of all mercury in Sweden, including amalgam dental fillings. California has passed legislation obliging dentists to inform patients of the mercury exposure from dental amalgam fillings.
More and more medical physicians and scientists are coming forth against the use of mercury fillings, with special consideration to children and unborn babies. Professor Maths Berlin - the Chair of the former International MAC Committee on mercury, a consultant to the W.H.O. on mercury, and Chair of the committee on dental amalgam mercury for the government of Sweden - advised the Swedish Government that the use of dental amalgam should be stopped in all of the countries of the European Union. Professor Berlins reputation in the field of mercury toxicology is certainly at least the equal to that of Dr. Clarkson. More and more, Dr. Clarkson is finding himself isolated from other mercury toxicology experts.

This is an issue that simply will not go away, in spite of the tremendous efforts of organized dentistry to combat it. There must be good reason! 
********************************************************************
(02/05/04) of my evaluation of the fallacy of Clarksons NEJM article.  by Dr. Chester YokoyamaAnalysis of "The Toxicology of Mercury" article in the NEJM by Thomas W. Clarkson, PhD, et al., Oct. 30, 2003. 

To understand the fallacy in Dr. Clarksons reasoning, I draw your attention to the statement that declares, "The problem is that mercury can inhibit various biochemical processes in vitro without having the same effect in vivo." This is true, but the opposite is more true. Biochemical processes inhibited in the diseased human, when reproduced in a lab by a causative agent, makes for good science and is an example of the fundamental scientific method. The fallacy lies in the assumption that lab studies attempt to prove that the results happen in vivo. It is the exact opposite. Scientists attempt to reproduce disease indicators that happen in the human body. The reproduction of known phenomena is scientific evidence of a connection between the causative agent and the disease.The "in vitro" study that Dr. Clarkson refers to is the Leong, et al, "Retrograde Degeneration of Neurite Membrane," Faculty of Medicine, University of Calgary, Canada. In this article, scientists show that a causative agent, Hg, caused the same things to happen to nerve cells as happens in the Alzheimers patients. The authors state, "We conclude that this visual evidence and previous biochemical data strongly implicate Hg as a potential etiological factor in neurodegeneration." It is only with prejudice and partiality that one can conclude that there is no evidence of connection. Clarksons conclusion, "Patients who have questions about the potential relation between Hg and degenerative diseases can be assured that the available evidence shows no connection." Clearly, the scientific paper (pier reviewed and published in the scientific journal, NeuroReport) concludes that there is evidence of connection between neurodegeneration and Hg.Leong C.C., ---Evidence, Hg, potential, degeneration, strongly implicates.Clarkson, T, ---Evidence, Hg, potential, degeneration, no connection?????

This federal law seems to show that the LSRO procedures are illegal.  This clearly indicates that we should be able to get copies of what is given to the scientific panel.