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  1. #1
    Join Date
    Jun 1999
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    Santa Fe, NM 87505, USA
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    ************************************************** **********

    http://groups.yahoo.com/group/aspartameNM/message/1143
    methanol [formaldehyde, formic acid] disposition: Bouchard M et al, full
    plain text, 2001: substantial sources are degradation of fruit pectins,
    liquors, aspartame, smoke: Murray 2005.05.30 2005.07.24 rmforall

    An earnest medical layman, I have been writing careful reviews of mostly
    mainstream medical research on aspartame toxicity for six years.

    http://groups.yahoo.com/group/aspartameNM/message/1155
    continuing aspartame debate in British Medical Journal, John Biffra, Bob
    Dowling, Nick Finer, Ian J Gordon: Murray 2005.02.09 rmforall

    http://groups.yahoo.com/group/aspartameNM/message/1108
    faults in 1999 July EPA 468-page formaldehyde profile:
    Elzbieta Skrzydlewska PhD, Assc. Prof., Medical U. of Bialystok, Poland,
    abstracts -- ethanol, methanol, formaldehyde, formic acid, acetaldehyde,
    lipid peroxidation, green tea, aging, Lyme disease:
    Murray 2004.08.08 rmforall

    In recent months I have become aware that evidence strongly shows that
    substantial methanol and thus formaldehyde and formic acid are released into
    humans from degradation of the pectins from fruits and vegetables by
    bacteria in the colon in many people. Whatever the source, the biochemical
    dispositions of methanol and its inevitable products, formaldehyde and
    formic acid, both potent, cumulative toxins, are actually largely unknown,
    according to the expert comprehensive review by Bouchard M et al, 2001.

    "Experimental studies on the detailed time profiles following controlled
    repeated exposures to methanol are lacking."

    "Thus, in monkeys and plausibly humans, a much larger fraction of body
    formaldehyde is rapidly converted to unobserved forms rather than passed on
    to formate and eventually CO2."

    "However, the volume of distribution of formate was larger than that of
    methanol, which strongly suggests that formate distributes in body
    constituents other than water, such as proteins."

    Their comprehensive review shows that there is little information about the
    details of methanol [formaldehyde and formic acid] dispositions in humans
    for long-term, chronic exposures. Their full text is given later in this
    post.

    Research on hangovers, largely caused by the conversion of methanol impurity
    in alcohol drinks into formaldehyde after about eight hours, after most of
    the ethanol has been eliminated, shows that a quarter to a half of those who
    get inebriated do not get hangovers. This shows very large individual
    variation in vulnerability to formaldehyde toxicity, so as a corollary,
    probably there will be many who are not markedly vulnerable to aspartame.

    I suggest that natural selection has given humans complex biochemical
    systems to store the large amounts of formaldehyde generated from pectins
    and to use them to attack pathogens. So far, I have not found any strong
    research to support this hypothesis. I hope to write a useful summary
    in the next few weeks.

    There are many substances, such as folic acid, that protect against
    formaldehyde toxicity.

    This long, complex review presents mainstream evidence for several
    ubiquitous, substantial sources of methanol and its inevitable chain of
    products, formaldehyde and formic acid, which I will initialize as "MCC",
    for Methanol Chain Compounds.

    Monte WC in his seminal summary review [1984] mentions that humans are
    uniquely vulnerable to the conversion of methanol into formaldehyde:

    "Fruit and vegetables contain pectin with variable methyl ester content.
    However, the human has no digestive enzymes for pectin [6, 25]
    particularly the pectin esterase required for its hydrolysis to methanol
    [26]."

    "Humans, due perhaps to the loss of two enzymes during evolution, are
    more sensitive to methanol than any laboratory animal; even the monkey
    is not generally accepted as a suitable animal model [42]."

    "The methyl ester bond of phenyalanine is the first
    to cleave due to its susceptibility to pancreatic enzymes [40].
    This is highly unusual; the methyl esters associated with pectin for
    instance are completely impervious to all human digestive enzymes [6]."

    "The greater toxicity of methanol to man is deeply rooted in the limited
    biochemical pathways available to humans
    for detoxification. The loss of uricase [EC 1.7.3.3.],
    formyl-tetrahydrofolate synthetase [EC 6.3.4.3.] [42]
    and other enzymes [18] during evolution sets man apart from all
    laboratory animals including the monkey [42]."

    "The importance of ethanol as an antidote to methanol toxicity in humans
    is very well established in the literature [46, 55]. The timely
    administration of ethanol is still considered a vital part of methanol
    poisoning management [11, 12, 19, 20, 50]. Ethanol slows the rate of
    methanol's conversion to formaldehyde and formate, allowing the body
    time to excrete methanol in the breath and urine. Inhibition is seen in
    vitro even when the concentration of ethyl alcohol was only 1/16th that
    of methanol [62]. The inhibitory effect
    is a linear function of the log of the
    ethyl alcohol concentration, with a 72% inhibition rate at only
    a 0.01 molar concentration of ethanol [2, 46].

    Oxidation of methanol, like that of ethanol, proceeds independently of
    the blood concentration, but at a rate only one seventh [20] to one
    fifth [12] that of ethanol.

    Folacin may play an important role in the metabolism of
    methanol by catalyzing the elimination of formic acid [41].
    If this process proves to be as protective for humans
    as has been shown in other organisms [50, 38]
    it may account, in part, for the tremendous variability of
    human responses to acute methanol toxicity. Folacin is a nutrient
    often found lacking in the normal human diet, particularly during
    pregnancy and lactation [14]."

    It is well known that our primate ancestors were highly adapted to a diet of
    fruits and vegetables, and thus had the enzyme systems to prevent toxicity
    from the inevitable methanol content and from methanol from the degradation
    of pectins by bacteria in the colon.

    Humans have been living in groups in lifelong close proximity with fire and
    smoke, a potent source of formaldehyde, for about 2 million years. Fire has
    ever since been essential for survival, as has been intimate enclosed group
    living, especially as homo erectus, Neanderthals, and moderns successively
    adapted to very cold habitats.

    Yet formaldehyde is among the most potent of toxins, and cumulative to boot.
    Yet intimate enclosed group living in a variety of environments promotes
    extreme exposure to a variety of contagious, infectious diseases. And yet,
    humans lack two enzymes that protect against Methanol Chain Compounds
    toxicities. What is an obvious evolutionary explanation for this?

    MCC toxicities must serve to prevent and treat contagious infections from
    bacteria, fungi, parasites, and possibly viruses. This would generate a
    potent positive selection pressure to cause humans to evolve the ability to
    have increased MCC exposures, and to be multiply adapted to tolerate MC
    toxicities.

    Wine and beer serve throughout history to protect against water bourne
    pathogens. For centuries formaldehyde has been used to protect medical
    scientists from highly infected cadaver tissues. What is the scientific
    literature about MCC and the various groups of contagious infectious agents?
    It is a testable hypothesis as to whether MCC in many types of people, with
    the inevitable complex variations of genetics and diet, impede many simple
    infectious agents more than they harm critical body processes in complex
    human cells.

    It may be that MCC are important unexamined co-factors that strongly affect
    research and treatment of many infectious diseases.

    We might find, for instance, that in many humans some infections cause
    reduction of folic acid or folate levels, and thus increased MCC levels.

    Many traditional societies treat diseases with exposure to smoke, whether in
    a hut with a wood fire, or in a temple with incense. Likewise, alcohol
    drinks have been widely used as remedies. Did the daily ration of grog in
    the British Navy serve to reduce infections in the close and dirty confines
    of life on wooden ships? In the trenches of World War I, the British also
    had a daily ration -- were their rates of infection lower
    than for troops that had little liquor?

    These questions throw an entirely new light, expansive, tantalizing, and
    unifying, on the often contentious and poorly researched issues of MCC
    toxicity, especially the aspartame controversy. It would also be ironic,
    but typical of the actual complex evolution of science, for tobacco and wood
    smoke to be shown to have some benefits for infectious diseases.

    http://groups.yahoo.com/group/aspartameNM/message/1140
    EPA Preliminary Remedial Goals, PRGs, 2003 Oct, air and tap water --
    methanol, formaldehyde, formic acid -- not mentioned is methanol from
    aspartame, dark wines and liquors: Murray 2004.11.20 rmforall

    http://groups.yahoo.com/group/aspartameNM/message/1141
    Nurses Health Study can quickly reveal the extent of aspartame [methanol,
    formaldehyde, formic acid] toxicity: Murray 2004.11.21 rmforall

    The Nurses Health Study is a bonanza of information about the health of
    probably hundreds of nurses who use 6 or more cans daily of diet soft
    drinks -- they have also stored blood and tissue samples from their immense
    pool of subjects.

    Dark wines and liquors, as well as aspartame, provide similar levels of
    methanol, above 100 mg daily, for long-term heavy users. Methanol is
    inevitably largely turned into formaldehyde, and thence largely into formic
    acid.

    Both products are toxic, and at this level of use, about 2 L daily,
    almost six 12-oz cans of diet drink, are above recent lifetime EPA
    safety limits in tap water for methanol and formaldehyde of respectively,
    for a 60 kg person, 30 mg and 9 mg daily.

    The immediate health effects for dark wines and liquors are the infamous
    "morning after" hangover, for which many informed experts cite as the major
    cause the conversion of the methanol impurity, over one part in ten thousand
    [red wine has 128 mg/L methanol], into formaldehyde and formic acid.
    Everyone knows the complex progression of symptoms at this level of
    long-term, chronic toxicity.

    Aspartame reactors have a very similar progression.

    If 1% of all people exposed to alcohol and/or aspartame are heavy users with
    symptoms, then there would easily be about 2 million cases in the USA alone.

    This is a public health emergency.

    At the very least, professionals and the public should be alerted to
    investigate their own exposure, and be given a chance to try a very safe,
    simple, inexpensive treatment for complex, intractable, progressive
    symptoms -- reducing or eliminating their intake.

    There are as well, many safe substances that prevent or treat the
    toxicities -- for example, high folic acid levels expedite the elimination
    of formaldehyde.

    These toxicities are largely uncontrolled co-factors that affect every
    disease and must confuse and impede many health research programs on all
    levels.

    People in high-pressure, critical occupations, such as pilots, nuclear plant
    operators, and national leaders, should certainly be alerted.

    Also, two careful studies show substantial methanol release from degradation
    of pectins by bacteria in the colon from fruits and vegetables -- a topic
    that deserves careful, thorough research.

    Due to my bias, based on detailed reviews by Monte WC [1984]
    and by Mark D Gold [2003], for months I have been discounting the
    startlingly high methanol levels reported in the abstract for Lindinger W
    [1997]. I had been reducing the values in their abstract from g to mg, an
    unwarrented "correction" by a factor of a thousand, only to find that
    thefull text study and their many related studies supply expert, robust
    results:

    Alcohol Clin Exp Res. 1997 Aug; 21[5]: 939-43.
    Endogenous production of methanol after the consumption of fruit.
    Lindinger W, Taucher J, Jordan A, Hansel A, Vogel W.
    Institut fur Ionenphysik, Leopold Franzens Universitat Innsbruck, Austria.

    After the consumption of fruit, the concentration of methanol in the human
    body increases by as much as an order of magnitude.
    This is due to the degradation of natural pectin [which is esterified with
    methyl alcohol] in the human colon.
    In vivo tests performed by means of proton-transfer-reaction mass
    spectrometry show that consumed pectin in either a pure form [10 to 15 g]
    or a natural form [in 1 kg of apples] induces a significant increase of
    methanol in the breath (and by inference in the blood) of humans.
    The amount generated from pectin [0.4 to 1.4 g] [ 400 to 1400 mg ]
    is approximately equivalent to the total daily endogenous production
    [measured to be 0.3 to 0.6 g/day] [ 300 to 600 mg ]
    or that obtained from 0.3 liters of 80-proof brandy
    [calculated to be 0.5 g]. [ 500 mg ]
    This dietary pectin may contribute to the development
    of nonalcoholic cirrhosis of the liver. PMID: 9267548

    Alcohol Clin Exp Res. 1995 Oct; 19[5]: 1147-50.
    Methanol in human breath.
    Taucher J, Lagg A, Hansel A, Vogel W, Lindinger W.
    Institut fur Ionenphysik, Universitat Innsbruck, Austria.

    Using proton transfer reaction-mass spectrometry for trace gas analysis of
    the human breath, the concentrations of methanol and ethanol have been
    measured for various test persons consuming alcoholic beverages and various
    amounts of fruits, respectively.
    The methanol concentrations increased from a natural [physiological] level
    of approximately 0.4 ppm up to approximately 2 ppm a few hours after eating
    about 1/2 kg of fruits,
    and about the same concentration was reached after drinking of 100 ml brandy
    containing 24% volume of ethanol and 0.19% volume of methanol.
    PMID: 8561283
    [ Corrected 2005.07.11:
    24 ml means 19 g ethanol, and 0.19 ml means 0.15 g = 150 mg methanol.
    One L diet soda has 61.5 mg methanol in the aspartame molecule, so 100 ml
    diet soda has 6.15 mg methanol, so the brandy has 24.4 times more methanol
    than diet soda. ]

    I urge Channing Laboratory and its participating universities to rapidly
    mount an in-house study to study the Nurses Health Study database for the
    hundreds of nurses who are long-term users, above 6 cans diet drinks daily,
    for correlations with every disease, as well as ubiquitous co-factors like
    wine and liquor, cigarette smoke, and fruits and vegetables. It could
    vastly serve the world public health to make the initial findings widely
    available immediately. The disparaged issue of aspartame toxicity could be
    swiftly made legitimate, and the resulting progress on all levels remarkably
    accelerated.

    A single scientist could do this.

    Comments pro and con are welcome. A convenient venue would be
    the moderated newsgroup: bionet.toxicology.

    http://groups.yahoo.com/group/aspartameNM/message/1162
    Santa Fe area physicians who oppose aspartame: Citizens Nutrition Council,
    Santa Fe: Murray 2005.03.29

    Rich Murray, MA Room For All rmforall@comcast.net
    1943 Otowi Road, Santa Fe, New Mexico 87505 USA 505-501-2298
    http://groups.yahoo.com/group/aspartameNM/messages
    184 members, 1,168 posts in a public searchable archive
    ************************************************** ***********

    http://groups.yahoo.com/group/aspartameNM/message/957
    safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
    Murray 2003.01.12 rmforall EU Scientific Committee on Food, a whitewash

    http://groups.yahoo.com/group/aspartameNM/message/1045
    http://www.holisticmed.com/aspartame...2-response.htm
    Mark Gold exhaustively critiques European Commission Scientific
    Committee on Food re aspartame [ 2002.12.04 ] 59 pages, 230 references

    "C. Public Relations, Aspartame, Methanol, and Formaldehyde

    Before we discuss what little the Committee did say related to aspartame and
    formaldehyde, it is important to answer all of the typical public relations
    statements from the manufacturer and their consultants who claim there is no
    problem with aspartame and formaldehyde. The answers provided below will be brief.
    Much more detailed and referenced answers can be found at ATIC (2001)
    on the Internet at:

    http://www.holisticmed.com/aspartame.../methanol.html
    "Scientific Abuse in Aspartame Research"

    Chart of Aspartame Manufacturer Public Relations Statements
    Related to Methanol and Formaldehyde

    Manufacturer Claim --- Independent Response

    Methanol is found in fruits and alcoholic beverages at higher levels than in
    aspartame products. --- Alcoholic beverages contain large amounts of
    ethanol [a protective factor] which allows methanol to be excreted before
    much of it is converted into formaldehyde [Leaf 1952, Liesivuori 1991, Roe
    1982].

    Fruit juices have protective factors as well that prevent formaldehyde
    poisoning. Fruit juices produce enough methanol to "qualify as significantly
    methanol-contaminated liquor" [Lindinger 1997] -- more methanol than what
    causes chronic
    health problems in occupational exposure [Kazeniac 1970,
    Kavet 1990, Frederick 1984, Kingsley 1954-55].

    Since we do not see chronic poisoning from fruit juices,
    they must contain protective factors as well.
    Fruit juices have ethanol as well as other possible protective factors."


    http://groups.yahoo.com/group/aspartameNM/message/870
    Aspartame: Methanol and the Public Interest 1984: Monte:
    Murray 2002.09.23 rmforall

    Dr. Woodrow C. Monte Aspartame: methanol, and the public health.
    Journal of Applied Nutrition 1984; 36 [1]: 42-54.
    [62 references] Professsor of Food Science
    Arizona State University, Tempe, Arizona 85287 woodymonte@xtra.co.nz
    ************************************************** ************

    http://groups.yahoo.com/group/aspartameNM/message/1143
    antiseptic? antifungal? antiviral? methanol [formaldehyde, formic acid]
    disposition: Bouchard M et al, full plain text, 2001: substantial sources
    are degradation of fruit pectins, liquors, aspartame, smoke: Murray
    2005.01.05 rmforall

    "That substantial amounts of methanol metabolites or by-products are
    retained for a long time is verified by Horton et al. [1992] who estimated
    that 18 h following an iv injection of 100 mg/kg of 14C-methanol in male
    Fischer-344 rats, only 57% of the dose was eliminated from the body.

    From the data of Dorman et al. [1994] and Medinsky et al. [1997], it can
    further be calculated that 48 h following the start of a 2-h inhalation
    exposure to 900 ppm of 14C-methanol vapors in female cynomolgus monkeys,
    only 23% of the absorbed 14C-methanol was eliminated from the body.

    These findings are corroborated by the data of Heck et al. [1983] showing
    that 40% of a 14C-formaldehyde inhalation dose remained in the body 70 h
    postexposure."

    "Exposure to methanol also results from the consumption of certain
    foodstuffs [fruits, fruit juices, certain vegetables, aspartame sweetener,
    roasted coffee, honey] and alcoholic beverages [Health Effects Institute,
    1987; Jacobsen et al., 1988]."

    "However, the severe toxic effects are usually associated with the
    production and accumulation of formic acid, which causes metabolic acidosis
    and visual impairment that can lead to blindness and death at blood
    concentrations of methanol above 31 mmol/l [Røe, 1982; Tephly and McMartin,
    1984; U.S. DHHS, 1993].

    Although the acute toxic effects of methanol in humans are well documented,
    little is known about the chronic effects of low exposure doses, which are
    of interest in view of the potential use of methanol as an engine fuel and
    current use as a solvent and chemical intermediate.

    Gestational exposure studies in pregnant rodents [mice and rats] have also
    shown that high methanol inhalation exposures [5000 or 10,000 ppm and more,
    7 h/day during days 6 or 7 to 15 of gestation] can induce birth defects
    [Bolon et al., 1993; IPCS, 1997; Nelson et al., 1985]."

    "The corresponding average elimination half-life of absorbed methanol
    through metabolism to formaldehyde was estimated to be
    1.3, 0.7-3.2, and 1.7 h."

    "Inversely, in monkeys and in humans, a larger fraction of body burden of
    formaldehyde is rapidly transferred to a long-term component.
    The latter represents the formaldehyde that [directly or after oxidation to
    formate) binds to various endogenous molecules..."

    "Animal studies have reported that systemic methanol is eliminated mainly by
    metabolism [70 to 97% of absorbed dose] and only a small fraction is
    eliminated as unchanged methanol in urine and in the expired air (< 3-4%)
    [Dorman et al., 1994; Horton et al., 1992].

    Systemic methanol is extensively metabolized by liver alcohol dehydrogenase
    and catalase-peroxidase enzymes to formaldehyde, which is in turn rapidly
    oxidized to formic acid by formaldehyde dehydrogenase enzymes
    [Goodman and Tephly, 1968; Heck et al., 1983; Røe, 1982; Tephly and McMartin, 1984].

    Under physiological conditions, formic acid dissociates to formate and
    hydrogen ions.

    Current evidence indicates that, in rodents, methanol is converted mainly by
    the catalase-peroxidase system whereas monkeys and humans metabolize
    methanol mainly through the alcohol dehydrogenase system [Goodman and
    Tephly, 1968; Tephly and McMartin, 1984].

    Formaldehyde, as it is highly reactive, forms relatively stable adducts with
    cellular constituents [Heck et al., 1983; Røe, 1982]."

    "The whole body loads of methanol, formaldehyde, formate, and unobserved
    by-products of formaldehyde metabolism were followed.

    Since methanol distributes quite evenly in the total body water, detailed
    compartmental representation of body tissue loads was not deemed necessary."

    "According to model predictions, congruent with the data in the literature
    [Dorman et al., 1994; Horton et al., 1992], a certain fraction of
    formaldehyde is readily oxidized to formate, a major fraction of which is
    rapidly converted to CO2 and exhaled, whereas a small fraction is excreted
    as formic acid in urine.

    However, fits to the available data in rats and monkeys of Horton et al.
    [1992] and Dorman et al. [1994] show that, once formed, a substantial
    fraction of formaldehyde is converted to unobserved forms.

    This pathway contributes to a long-term unobserved compartment.

    The latter, most plausibly, represents either the formaldehyde that
    [directly or after oxidation to formate] binds to various endogenous
    molecules [Heck et al., 1983; Røe, 1982]
    or is incorporated in the tetrahydrofolic-acid-dependent one-carbon pathway
    to become the building block of a number of synthetic pathways [Røe, 1982;
    Tephly and McMartin, 1984].

    That substantial amounts of methanol metabolites or by-products are retained
    for a long time is verified by Horton et al. [1992] who estimated that 18 h
    following an iv injection of 100 mg/kg of 14C-methanol in male Fischer-344
    rats, only 57% of the dose was eliminated from the body.

    From the data of Dorman et al. [1994] and Medinsky et al. [1997], it can
    further be calculated that 48 h following the start of a 2-h inhalation
    exposure to 900 ppm of 14C-methanol vapors in female cynomolgus monkeys,
    only 23% of the absorbed 14C-methanol was eliminated from the body.

    These findings are corroborated by the data of Heck et al. [1983] showing
    that 40% of a 14C-formaldehyde inhalation dose remained in the body 70 h
    postexposure.

    In the present study, the model proposed rests on acute exposure data, where
    the time profiles of methanol and its metabolites were determined only over
    short time periods [a maximum of 6 h of exposure and a maximum of 48 h
    postexposure].

    This does not allow observation of the slow release from the long-term
    components.

    It is to be noted that most of the published studies on the detailed
    disposition kinetics of methanol regard controlled short-term [iv injection
    or continuous inhalation exposure over a few hours] methanol exposures in
    rats, primates, and humans [Batterman et al., 1998; Damian and Raabe, 1996;
    Dorman et al., 1994; Ferry et al., 1980; Fisher et al., 2000; Franzblau et
    al., 1995; Horton et al., 1992; Jacobsen et al., 1988; Osterloh et al.,
    1996; Pollack et al., 1993; Sedivec et al., 1981; Ward et al., 1995; Ward
    and Pollack, 1996].

    Experimental studies on the detailed time profiles following controlled
    repeated exposures to methanol are lacking."

    "Thus, in monkeys and plausibly humans, a much larger fraction of body
    formaldehyde is rapidly converted to unobserved forms rather than passed on
    to formate and eventually CO2."

    "However, the volume of distribution of formate was larger than that of
    methanol, which strongly suggests that formate distributes in body
    constituents other than water, such as proteins.

    The closeness of our simulations to the available experimental data on the
    time course of formate blood concentrations is consistent with the volume of
    distribution concept [i.e., rapid exchanges between the nonblood pool of
    formate and blood formate]."

    "Also, background concentrations of formate are subject to wide
    interindividual variations [Baumann and Angerer, 1979; D'Alessandro et al.,
    1994; Franzblau et al., 1995; Heinrich and Angerer, 1982; Lee et al., 1992;
    Osterloh et al., 1996; Sedivec et al., 1981]."

    http://www.toxsci.oupjournals.org/cg.../full/64/2/169

    Toxicological Sciences 64, 169-184 [2001]
    Copyright © 2001 by the Society of Toxicology

    BIOTRANSFORMATION AND TOXICOKINETIC

    A Biologically Based Dynamic Model for Predicting the Disposition of
    Methanol and Its Metabolites in Animals and Humans

    Michèle Bouchard *, #,1, bouchmic@magellan.umontreal.ca

    Robert C. Brunet, # brunet@dms.umontreal.ca

    Pierre-Olivier Droz, #

    and Gaétan Carrier* gaetan.carrier@umontreal.ca

    * Department of Environmental and Occupational Health, Faculty of Medicine,
    Université de Montréal, P.O. Box 6128, Main Station, Montréal, Québec,
    Canada, H3C 3J7;

    # Institut Universitaire romand de Santé au Travail, rue du Bugnon 19,
    CH-1005, Lausanne, Switzerland, and

    # Département de Mathématiques et de Statistique and Centre de Recherches
    Mathématiques, Faculté des arts et des sciences, Université de Montréal,
    P.O. Box 6128, Main Station, Montréal, Québec, Canada, H3C 3J7

    NOTES

    1 To whom correspondence should be addressed at Département de santé
    environnementale et santé au travail, Université de Montréal, P.O. Box 6128,
    Main Station, Montréal, Québec, H3C 3J7, Canada. Fax: (514) 343-2200.
    E-mail: bouchmic@magellan.umontreal.ca

    Received May 10, 2001; accepted August 28, 2001

    ABSTRACT
    TOP
    ABSTRACT
    INTRODUCTION
    METHOD AND MODEL PRESENTATION
    RESULTS
    DISCUSSION
    APPENDIX
    REFERENCES
    ************************************************** ************


    http://groups.yahoo.com/group/aspartameNM/message/1145
    EPA Preliminary Remedial Goals (PRG) 2003 Oct, air and tap water --
    methanol, formaldehyde, formic acid -- sources omitted are methanol from
    aspartame, dark wines and liquors, fruit pectins: Murray 2005.01.18 rmforall

    [ Introductory summary by Rich Murray: They gave the same data on
    2004.10.27. I have put the data for methanol, formaldehyde, and formic acid
    together in this plain text version, since oral ingestion of methanol,
    whether from the 11% methanol component of aspartame, or the similar level
    of methanol impurity in dark wines and liquors, about one part in ten
    thousand, inevitably leads to full absorption in the human GI tract. Some
    is excreted, but most is largely converted into formaldehyde, and thence
    largely converted into formic acid -- both potent, culmulative toxins that
    affect all cells and tissues.

    Very large amounts of methanol are released by bacterial degradation of
    pectins from fruits and vegetables in the human colon:

    http://groups.yahoo.com/group/aspartameNM/message/1143
    antiseptic? antifungal? antiviral? methanol (formaldehyde, formic acid)
    disposition: Bouchard M et al, full plain text, 2001: substantial sources
    are degradation of fruit pectins, liquors, aspartame, smoke: Murray
    2005.01.05 rmforall

    So, the key fact here is the RfDo, a lifetime safe level for daily ingested
    oral exposure, which for these three chemicals are:

    0.5 mg, 0.15 mg, and 2 mg per kg per day, which for a smallish adult of 60
    kg, is 30 mg, 9 mg, and 120 mg daily for methanol, formaldehyde, formic
    acid.

    http://groups.yahoo.com/group/aspartameNM/message/1141
    Nurses Health Study can quickly reveal the extent of aspartame (methanol,
    formaldehyde, formic acid) toxicity: Murray 2004.11.21 rmforall

    http://groups.yahoo.com/group/aspartameNM/message/1108
    faults in 1999 July EPA 468-page formaldehyde profile:
    Elzbieta Skrzydlewska PhD, Assc. Prof., Medical U. of Bialystok, Poland,
    abstracts -- ethanol, methanol, formaldehyde, formic acid, acetaldehyde,
    lipid peroxidation, green tea, aging, Lyme disease:
    Murray 2004.08.08 rmforall

    Rich Murray, MA Room For All rmforall@comcast.net
    1943 Otowi Road, Santa Fe, New Mexico 87505 USA 505-501-2298
    http://groups.yahoo.com/group/aspartameNM/messages
    184 members, 1,168 posts in a public searchable archive

    The moderated newsgroup, bionet.toxicology , has accepted 32 of my long
    reviews since March 24 2004:

    Dr. Charles "Chuck" A. Miller III rellim@tulane.edu
    Associate Professor of Environmental Health Sciences
    374 Johnston Building, SL29
    Tulane Univ. School of Public Health and Tropical Medicine
    1430 Tulane Avenue New Orleans, LA 70112 (504)585-6942
    Bionet.toxicology news group http://www.bio.net/hypermail/toxicol/current

    [ NutraSweet, Equal, Canderel, Benevia, E951 ]

    http://groups.yahoo.com/group/aspartameNM/message/927
    Donald Rumsfeld, 1977 head of Searle Corp., got aspartame FDA approval:
    Turner: Murray 2002.12.23 rmforall

    A very detailed, highly credible account of the dubious approval process for
    aspartame in July, 1981 is part of the just released two-hour documentary
    "Sweet Misery, A Poisoned World: An Industry Case Study of a Food Supply
    In Crisis" by Cori Brackett: cori@soundandfuryproductions.com
    http://www.soundandfuryproductions.com/ 520-624-9710
    2301 East Broadway, Suite 111 Tucson, AZ 85719

    http://groups.yahoo.com/group/aspartame/messages
    Aspartame Victims Support Group Edward Bryant Holman, Chief Moderator
    840 members, 18,328 posts in a public, searchable archive
    http://www.presidiotex.com/aspartame/ bryanth@presidiotex.net

    http://www.HolisticMed.com/aspartame mgold@holisticmed.com
    Aspartame Toxicity Information Center Mark D. Gold also Co-Moderator
    12 East Side Drive #2-18 Concord, NH 03301 603-225-2110
    http://www.holisticmed.com/aspartame.../methanol.html
    "Scientific Abuse in Aspartame Research"

    http://groups.yahoo.com/group/aspartameNM/message/957
    safety of aspartame Part 1/2 12.4.2: EC HCPD-G SCF:
    Murray 2003.01.12 rmforall EU Scientific Committee on Food, a whitewash

    http://groups.yahoo.com/group/aspartameNM/message/1045
    http://www.holisticmed.com/aspartame...2-response.htm
    Mark Gold exhaustively critiques European Commission Scientific
    Committee on Food re aspartame ( 2002.12.04 ): 59 pages, 230 references

    http://www.sweetpoison.com/ Janet Starr Hull, PhD, CN jshull@sweetpoison.com

    http://groups.yahoo.com/group/aspartameNM/message/1092
    Janet Starr Hull, who also had Graves disease in 1991, told Justin Dumais to
    quit aspartame: Murray 2004.06.12 rmforall

    http://www.aspartamesafety.com marystod@airmail.net
    Mary Nash Stoddard, Founder
    Aspartame Consumer Safety Network and Pilot Hotline [1987-2004]
    P.O. Box 2001 Frisco, TX 75034 1-214-387-4001 [ 25 miles N of Dallas ]

    http://groups.yahoo.com/group/aspartameNM/message/1131
    genotoxicity of aspartame in human lymphocytes 2004.07.29 full plain text,
    Rencuzogullari E et al, Cukurova University, Adana, Turkey
    2004 Aug: Murray 2004.11.06 rmforall
    ************************************************** **********

    http://groups.yahoo.com/group/aspartameNM/message/1123
    genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor;
    sucralose, cyclamate, saccharin bad: Sasaki YF, Aug, Dec 2002:
    Rencuzogullari E et al, Aug 2004: Murray 2003.01.27, 2004.10.17 rmforall

    "However, it must be taken into account that ASP induced the CA and
    micronuclei formation in a dose-dependent manner.

    It is not possible to conclude that ASP is safe according to these results.

    Therefore, it is necessary to be careful when using it in food and beverages
    as a sweetener."

    Drug Chem Toxicol. 2004 Aug; 27(3): 257-68.
    Genotoxicity of aspartame. reyyup@mail.cu.edu.tr
    Rencuzogullari E, Tuylu BA, Topaktas M, Ila HB, Kayraldiz A, Arslan M, Diler
    SB. Biology Department, Faculty of Arts and Sciences, Natural and Applied
    Sciences Institute, Cukurova University, Adana, Turkey.
    ************************************************** **********

    http://groups.yahoo.com/group/aspartameNM/message/1088
    Murray, full plain text & critique:
    chronic aspartame in rats affects memory, brain cholinergic receptors, and
    brain chemistry, Christian B, McConnaughey M et al, 2004 May:
    2004.06.05 rmforall

    Pharmacol Biochem Behav. 2004 May; 78(1): 121-7.
    Chronic aspartame affects T-maze performance, brain cholinergic receptors
    and Na(+),K(+)-ATPase in rats.
    Christian B, McConnaughey K, Bethea E, Brantley S, Coffey A, Hammond L,
    Harrell S, Metcalf K, Muehlenbein D, Spruill W, Brinson L, McConnaughey M.
    Department of Pharmacology, Brody School of Medicine, East Carolina
    University, Greenville, NC 27858, USA;
    North Carolina School of Science and Mathematics, Durham, NC 27811.
    http://www.ecu.edu/pharmacology/facu...onnaughey.html
    Mona M. McConnaughey, Ph.D. Research Assistant Professor
    Department: PHARMACOLOGY & TOXICOLOGY
    Office: Brody Medical Science 6E-120A 252-744-2756
    MCCONNAUGHEYM@mail.ecu.edu

    This study demonstrated that chronic aspartame consumption in rats can lead
    to altered T-maze performance and increased muscarinic cholinergic receptor
    densities in certain brain regions.
    Control and treated rats were trained in a T-maze to a particular side and
    then periodically tested to see how well they retained the learned response.
    Rats [ 12 rats ] that had received aspartame
    (250 mg/kg/day) in the drinking water for 3 or 4 months showed a significant
    increase in time to reach the reward in the T-maze, suggesting a possible
    effect on memory due to the artificial sweetener.
    Using [(3)H]quinuclidinyl benzilate (QNB) (1 nM) to label muscarinic
    cholinergic receptors and atropine (10(-6) M) to determine nonspecific
    binding in whole-brain preparations,
    aspartame-treated rats showed a 31% increase in receptor numbers when
    compared to controls.
    In aspartame-treated rats, there was a significant increase in muscarinic
    receptor densities in the
    frontal cortex, midcortex, posterior cortex, hippocampus, hypothalamus and
    cerebellum of 80%, 60%, 61%, 65%, 66% and 60%, respectively.
    The midbrain was the only area where preparations from aspartame-treated
    rats showed a significant increase in Na(+),K(+)-ATPase activity.
    It can be concluded from these data that long-term consumption of aspartame
    can affect T-maze performance in rats and alter receptor densities or
    enzymes in brain. PMID: 15159141
    ************************************************** ************

    http://groups.yahoo.com/group/aspartameNM/message/1067
    eyelid contact dermatitis by formaldehyde from aspartame, AM Hill & DV
    Belsito, Nov 2003: Murray 3.30.4 rmforall [ 150 KB ]

    Rich Murray, MA Room For All rmforall@comcast.net
    1943 Otowi Road, Santa Fe, New Mexico 87505 USA 505-986-9103

    [ Comments by Rich Murray are in square brackets. To increase the
    readability of the dense, specialized, condensed text of a brief scientific
    letter (usually not peer reviewed), I have added spacing without altering
    text, while correcting minor typos.

    I then offer some critical analyses and extensions of the references, since
    the relevant scientific literature is contaminated by long-term, systematic
    influence by corporate vested interests. ]

    "A 60-year-old Caucasian woman presented with a 6-month history of eyelid
    dermatitis...

    By strictly avoiding formaldehyde and all formaldehyde releasers for the
    next 3 weeks, she improved only slightly.

    Her problem, however, was subsequently solved when a local pharmacist
    advised her to avoid aspartame.

    She had begun using an aspartame-based artificial sweetener 5 months prior
    to the onset of her dermatitis. [ 12 months of low-level aspartame use until
    stopping. ]

    Within 1 week of discontinuing the aspartame, her eyelid dermatitis resolved
    completely and has not recurred over 18 months without specific
    treatment....

    Our patient was consuming an average of 80 mg (1.13 mg/kg) of aspartame
    daily, well below the levels previously studied."

    [ A packet of tabletop sweetener gives 37 mg aspartame, while a 12 oz diet
    soda gives 200 mg aspartame. An aspartame reactor can have immediate
    strong symtoms from an under-the-tongue wafer with 4 mg aspartame.
    (Appendix A, for comments, abstracts, and links.) ]

    Contact Dermatitis. 2003 Nov; 49(5): 258-9.
    Systemic contact dermatitis of the eyelids caused by formaldehyde derived
    from aspartame?
    Hill AM, Belsito DV. DBelsito@kumc.edu
    Division of Dermatology, University of Kansas Medical Center, 3901 Rainbow
    Blvd., Kansas City, KS 66160, USA. PMID: 14996049

    A. Michele Hill and Donald V. Belsito
    Division of Dermatology, University of Kansas Medical Center
    3901 Rainbow Blvd., Kansas City, KS 66160, USA [ (Appendix B, for more
    abstracts by Donald V. Belsito, selections, and institutions) ]

    Key Words: allergic contact dermatitis; aspartame; eyelids; formaldehyde;
    systemic contact dermatitis.

    Formaldehyde is a common and ubiquitous contact allergen.
    Sources of exposure include hair and skin care products, cosmetics, topical
    medications, permanent press clothing, cleaning agents, disinfectants, paper
    and even smoke. [ Also, new buildings, mobile homes, furniture, carpets,
    drapes, particleboard, medical facilities, methanol, aspartame, dimethyl
    dicarbonate, dark wines and liquors, degradation by bacteria in the colon of
    pectins from fruits and vegetables ]

    Sensitization is reported in between 2.2 and 9.6% of patients patch tested
    (1,2).
    [ (Appendix C, for abstracts on rates of formaldehyde sensitivity in control
    groups, as a possible first estimate of the impact of widespread exposure to
    aspartame since 1981.) ]
    ************************************************** ************

    http://groups.yahoo.com/group/aspartameNM/message/1016
    President Bush & formaldehyde (aspartame) toxicity: Ramazzini Foundation
    carcinogenicity results Dec 2002: Soffritti: Murray 8.3.3 rmforall

    p. 88 "The sweetening agent aspartame hydrolyzes in the gastrointestinal
    tract to become free methyl alcohol, which is metabolized in the liver
    to formaldehyde, formic acid, and CO2. (11)"
    Medinsky MA & Dorman DC. 1994; Assessing risks of low-level
    methanol exposure. CIIT Act. 14: 1-7.

    Ann N Y Acad Sci. 2002 Dec; 982: 87-105.
    Results of long-term experimental studies on the carcinogenicity of
    formaldehyde and acetaldehyde in rats.
    Soffritti M, Belpoggi F, Lambertin L, Lauriola M, Padovani M, Maltoni C.
    Cancer Research Center, European Ramazzini Foundation for Oncology and
    Environmental Sciences, Bologna, Italy. crcfr@tin.it

    Formaldehyde was administered for 104 weeks in drinking water supplied
    ad libitum at concentrations of 1500, 1000, 500, 100, 50, 10, or 0 mg/L
    to groups of 50 male and 50 female Sprague-Dawley rats beginning at
    seven weeks of age.
    Control animals (100 males and 100 females) received tap water only.
    Acetaldehyde was administered to 50 male and 50 female Sprague-Dawley
    rats beginning at six weeks of age at concentrations of 2,500, 1,500,
    500, 250, 50, or 0 mg/L.
    Animals were kept under observation until spontaneous death.
    Formaldehyde and acetaldehyde were found to produce an increase in total
    malignant tumors in the treated groups and showed specific carcinogenic
    effects on various organs and tissues. PMID: 12562630

    Surely the authors deliberately emphasized that aspartame is well-known
    to be a source of formaldehyde, which is an extremely potent, cumulative
    toxin, with complex, multiple effects on all tissues and organs.

    This is even more significant, considering that they have already tested
    aspartame, but not yet released the results:

    p. 29-32 Table 1: The Ramazzinni Foundation Cancer Program
    Project of Long-Term Carcinogenicity Bioassays: Agents Studied

    No. No. of Bioassays Species No. Route of Exposure
    108. "Coca-Cola" 4 Rat 1,999 Ingestion, Transplantal Route

    109. "Pepsi-Cola" 1 Rat 400 Ingestion
    110. Sucrose 1 Rat 400 Ingestion
    111. Caffeine 1 Rat 800 Ingestion
    112. Aspartame 1 Rat 1,800 Ingestion

    http://members.nyas.org/events/confe...f_02_0429.html
    Soffritti said that Coca-Cola showed no carcinogenicity.

    It may be time to disclose these important aspartame results.
    ************************************************** **********
    Send blank post to: <br />aspartameNM-subscribe@onelist.com to join<br />free,open, list with searchable archives for toxicity issues.<br />Richard \"Rich\" T. Murray Room For All 1943 Otowi Road Santa Fe, NM 87505<br />rmforall@comcast.net 505-501-2298

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