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December 17, 2004 Dear Prof. Kauffman, Recently it has come to our attention that you are distributing an article in which you attribute statements to me which were never, ever made, and are in direct contradiction to what I, in fact, did state in my communication with you. I will post this response, as well as the original communication, on our website. Thus, any of our 30,000 daily readers have a chance to make up their own mind on this issue. In this article, somewhat dressed up as a "review" of our research, you wrote that we (PFPC) assert that "all fluorinated organic compounds are toxic because they lead to fluoride ion." This was never, ever stated - and - is the direct opposite to what was actually said. As your article states so many untruths, it would take way too much time to address it all - time which I couldn't possibly give you at the moment. However, I will address comments that you made about some of the citations which were sent to you, and the manner in which you chose to misrepresent them. In your article you state, "Asked for evidence on the toxicity of fluorinated drugs, Andreas Schuld e-mailed citations to 13 papers. Ten of the 13 were published in or before 1952." The 13 citations I forwarded were NOT in response to a question "asking for evidence on the toxicity of fluorinated drugs"; they were related specifically to the pharmacological effects of fluoride compounds (some of which are now commonly used in drugs) upon thyroid hormone activity, as was clearly stated by myself. I gave the date of the data to show you how long this knowledge has been around. Had you actually asked for any evidence of toxicity of fluorinated drugs, I could have sent you hundreds, if not thousands, of citations. You wrote: Citations from the 1930s showed the toxicity of sodium fluoride from its interference with thyroid hormone biosynthesis (Kraft, 1937a), and a comparison of analytical methods for fluorine in fluoro compounds (Kraft, 1937b). Kraft's first 1937 paper (1937a) did not just show "the toxicity of sodium fluoride from its interference with thyroid hormone biosynthesis", it compared THREE fluoro-compounds (sodium fluoride, fluorobenzoic acid, fluorotyrosine) upon tadpole metamorphosis, clearly showing the point I made to you that ALL fluoro-compounds inhibit thyroid hormone activity, the difference being a matter of amplitude. In case you don't know (and you obviously don't, nor understand) all metamorphosis in amphibia anura is controlled by thyroid hormone (T3). The second Kraft paper (1937b) was NOT just a "comparison of analytical methods for fluorine in fluoro compounds", it also measured the fluoride component of drugs which were commonly used in the treatment of Basedow's Disease (hyperthyroidism), such as Solvitren as Tyronorman, as well as the fluoride in human blood after taking such drugs. (Again - because you don't know - it was not known at the time if there was any fluoride at all in these drugs. It was only after May suggested that there must be some fluoride in there - firmly believing that fluoride was the reason for any anti-thyroid effects of these drugs - that they were investigated). Had you actually read the papers I wouldn't have to state this. You wrote: Another from 1949 showed that that 3-fluoro-5-bromo(or iodo)tyrosine were not very toxic in mice, and 5 other fluorophenyl compounds even less so (Euler et al., 1949). This paper by Euler et al. did NOT state at all what you say it does. It has very many important findings, not the least of which is that ALL fluoro-compounds acted on liver glycogen, only differing in amplitude. It investigated 7 fluoro-compounds and their effects on teeth, bone, liver, kidney, thyroid, parathyroid, and adrenal glands. How anybody can read this paper and state what you did is quite remarkable!! You wrote: Papers by Georg Litzka confirmed the toxicity of 3-fluorotyrosine and 3,5-difluorotyrosine, including in humans, but this is a special case where these amino acid derivatives interefere with thryroid hormone biosynthesis (Litzka, 1936; 1937a; 1937b). Litzka's papers are very extensive investigations on the effects of fluorotyrosine and the possible mechanism behind its effects in the very successful treatment of hyperthyroidism, specifically as it affected glycolysis in liver and skeletal muscle. That this is not "a special case where these amino acid derivatives interefere with thryroid hormone biosynthesis" should have been clear to you, had you actually read the papers by Euler, Eichler, Kraft etc.. You wrote: One of the papers cited reported that 3-fluorotyrosine was more toxic to rats than inorganic fluoride (Euler, 1942). The 1942 paper by Euler et al. showed that fluorotyrosine and sodium fluoride had identical effects on 'calcium crystal deformation’ seen in bone and teeth. To quote from my original e-mail: Already in the 1940s Prof. Euler and colleagues from the University of Breslau were able to cause identical bone and enamel defects with organic fluoride compounds as are established to occur with inorganic ones. However, there was no dissociation of the compounds, hence no "free" fluoride was being stored anywhere. The investigation showed identical "calcium crystal deformation" as seen with inorganic fluoride. But you have no real answer to that, do you? Again, how you can possibly state that we assert that "all fluorinated organic compounds are toxic because they lead to fluoride ion" is beyond me. You wrote: One paper described syntheses of tyrosine analogs that were thyroid hormone antagonists in mice without evidence that fluoride ion was formed in vivo (Kraft, 1951). More nonsense. Despite the fact that it was never a concern of ours if any "fluoride ion" was formed, the work describes the synthesis of various fluoride compounds which were undertaken to specifically investigate if other fluorocompounds had similar antithyroid effects as fluorobenzoic acid and fluorotyrosine (which had been the first line of drug treatment in Basedow in the 1940s.) In addition, the amplitude in toxicity of various fluoride compounds was measured and compared. You wrote: Another paper had other syntheses, including that of the relatively non-toxic (to mice) 5-fluorosalicylic acid, an aspirin analog (Kraft, 1952). This work is a continuation of the 1951 work, and again - as stated by the authors - was done to investigate more fluoro-compounds to see a) if they were also able to lower the basal metabolic rate [Ed.: lower thyroid status], and b) if they showed antibiotic properties. 18 different compounds were investigated, and their synthesis described. (Kraft was a pharmacist for Knolls) You wrote: Another described the toxicity of sodium fluoride and phenylmethanesulfonyl fluoride and its analogs (Bollen, 1988). The toxicity of the former is well-known, and it is clear to a chemist that the S-F bond in the latter will yield fluoride ion on hydrolysis, so nothing new is found here. Bollen and Stalmans' work was cited, again, specifically in relation to the "free fluoride" or "release of fluoride ion" hypothesis. Bollen, as mentioned in my original e-mail to you, investigated PMSF and NaF- activity on modulators of glycogen-bound protein phosphatase in the liver, where a majority of thyroid hormone conversion (deiodination -> T4 to T3) occurs. The authors wrote: "The effectiveness of the proteinase inhibitor was not due to production You wrote: Regarding Cipro and the study by Pradhan et al, "The actual elevation of fluoride in serum was from 0.08 to 0.21 ppm in 12 hours, and could not account for more than a fraction of the fluorine (23 mg) in 400 mg doses of ciprofloxacin. " Besides the fact that it was not - again - a question of how much fluoride was liberated, it shows here that you know very little, if anything, about the importance of serum fluoride levels, be it peak or steady-state, in a toxicity assessment. For your info, in India where the study took place, 0.02 mg/L (ppm) is the upper limit for fluoride in serum for fluorosis diagnosis/assessments. If you think that serum peak levels of 0.21 [Ed.:more than 10 times as high!] are not important, I suggest you take up gardening or choral singing instead of dealing with fluoride toxicity issues. Either that or stick to 'chemistry', whatever that may mean to you. Please leave fluoride toxicology to others. Your intentional misinterpretation of what I wrote to you is, quite frankly, despicable. Have a nice and reflective holiday season, Andreas Schuld Click here to view Dr. Kauffman’s article... Other related links: Organic Fluorides & Thyroid
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