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UK COT chronic methanol toxicity in diet, 2011 July, free full text 22 pages -- earnest critical comments, applying the WC Monte methanol formaldehyde ADH1 enzyme paradigm: Rich Murray 2013.12.09

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  • Rich Murray
    UK COT chronic methanol toxicity in diet, 2011 July, free full text 22 pages -- earnest critical comments, applying the WC Monte methanol formaldehyde ADH1
    Message 1 of 1 , Dec 9, 2013
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      UK COT chronic methanol toxicity in diet, 2011 July, free full text 22 pages -- earnest critical comments, applying the WC Monte methanol formaldehyde ADH1 enzyme paradigm: Rich Murray 2013.12.09


      free full text, 245 page EFSA draft report on methanol toxicity 2013.01.08 ]


      Brief Summary:

      The half life of methanol in human blood is about 3 hours. Actually,
      a huge oral dose can saturate the catalase defense system in rats,
      resulting in their ADH1 enzyme making methanol into toxic
      formaldehyde inside cells in many tissues, whereas in humans only,
      whose defective catalase enzyme fails to safely metabolize
      formaldehyde inside the many protective peroxisomes in every cell, the
      ADH1 enzyme, in high levels in 19 specific tissues, quickly turns
      bloodborne methanol into uncontrolled free floating highly toxic
      formaldehyde inside cells, according to Prof. Woodrow C. Monte, Food
      Science and Nutrition, Arizona State University, retired 2004, in textbook
      "While Science Sleeps" 2012 January, with 2 free chapters, "Multiple
      Sclerosis" and "Autism and other birth defects", summary in Medical
      Hypothesis 2010 (not peer reviewed), 3 articles from Fitness Life,
      fall 2007, other articles, audio and video lectures and interviews,
      slideshows, backed by a free online archive of 782 mostly full text
      medical research references:

      Monte W.,
      Methanol: A chemical Trojan horse as the root of the inscrutable U.
      Med Hypotheses 2010;74(3):493-6.



      Preamble:

      Like most intelligent world citizens, my training in medical research is nil, so, as a volunteer information activist on the Net for 14 years, my strategy has been to earn credibility by providing busy professionals with conscientious, civil, fair, balanced, long, detailed, often primary source, information, with relevant background and contact information for public players, in the spirit of collegial scientific discourse based on reason and quality evidence.

      Toxins in foods, often tasty, with complex effects, often addictive, often gradual and long delayed, pose major challenges for our world -- in recent centuries, lead, sugar, ethanol, tobacco, caffeine, salt, processed starches,  animal proteins and fats, and a host of additives are now well known as hazardous. 

      Biology is always complex, and research costly, painstaking, and slow, with a typical time scale of decades, while global operations generate jobs and huge profits as they invent and spread a host of largely untested substances every few years.  These chaotic processes are unpredictably tragic.  Diet related diseases cause most human illness and death, far more than accidents, suicide, murder, and war --  themselves often promoted by neurotoxins. 

      The corrective protective processes in our world are slow, erratic, disorganized, underfunded, neglected, with low levels of personal and organizational motivation.   It took many decades to close down lead in USA gasoline and paint, while tobacco is still spreading worldwide.  Usually, people change diet slowly -- due to ingrained personal habits, family cultures, social conventions, cunning advertising that sustains huge profits for global businesses, the increasing complexity of medical evidence, higher prices, limited availability of new foods, compromised regulators, and poorly informed medical authorities.

      We see in recent years a major success in banning transfats, while this week, age 71, I stopped using folic acid and iron supplements -- a few of you will be quick to Google them for yourself. Healthy and safe food, drink, environment, and society are becoming prominent issues in all forms of media and all levels of government.  Public figures are embracing organic vegan diet.  The exponential acceleration of all forms of social media and biology hugely widens the reality of positive collaboration for huge mutual benefit by all players, from citizens to global organizations, while allowing them to create and share with light speed awesome realms of evidence.  The actual human harm and social costs of dietary toxins will be everyone's business in the emerging world social collaboration.

      My efforts since 1999 have been aimed at serving this benign global harmonizing, demonstating what one citizen can do by freely scattering good seed to the winds of change.

      Aspartame has been contentious for four decades.  Prof. Woodrow C. Monte, Food Science and Nutrition, Arizona State University, retired 2004, an expert activist since 1983, has morphed the issue to a whole new level since fall 2007 with his breakthrough paradigm of methanol toxicity via conversion to uncontrolled formaldehyde right inside cells by ADH1 enzyme, in high levels in 20 tissues in humans only, the only creature lacking a functioning biochemical defense -- humans are ten to a hundred times more vulnerable.  For each vulnerable tissue, there are one or more modern chronic ailments, ranging from Alzheimers, autism, atherosclerosis, arthritis to diabetes, multiple sclerosis, and to many cancers and birth defects -- inevitably multiple co-factors are involved, yet methanol (wood alcohol) very probably is the stealth agent that circulates to every cell in the body and fetus every minute via the blood with half-life 3 hours.

      Ethanol (ordinary drinking alcohol) is a strong antidote, binding to the ADH1 enzyme, preventing any methanol from being made into free floating, uncontrolled formaldehyde within defenseless human cells.  Dark wines and liquors have over 100 mg/L methanol impurity, so as soon as the ethanol, with blood half-life only 1/3 hour, dwindles to near zero, can the methanol suddenly start being made into formaldehyde -- witness the fact that alcohol hangovers only start in "the morning after the night before", when a few residual mg/L methanol in blood becomes formaldehyde inside the cells of the inner walls of blood vessels at the bottom of the brain, setting off headache with aching eyes and blurry vision.

      A major puzzle in recent years has been that many modern chronic human diseases have about half the symptoms for those who use alcohol once daily, compared to those who never drink -- the methanol paradigm explains this.  This line of evidence also applies to the many modern chronic human diseases known to be associated with cigarette smoke, since a pack gives 40 mg, as much methanol as 2 cans of aspartame diet drink.

      When methanol (wood alcohol) was finally highly purified about 1900, it was a better solvent than ethanol, and, being untaxed, was far cheaper, and so became widely used for flavors and medicines, as careful tests on a variety of animals showed it was safer than ethanol.  Within a few years physicians published detailed case reports of human blindness and deaths, but it was not until after 1940 that it was shown that humans were uniquely vulnerable -- not true for any other simple toxin.

      Monte gives a reference that as little as 3 grams can be lethal for a 70 kg man, based on a clinical trial. Well, formaldehyde toxicity is cumulative, since it binds firmly to nearby DNA, RNA, and proteins within the cell -- the basis for embalming -- so over a month, 3 grams spread out over 30 days is 100 mg daily, as much as 5 diet drinks or 2.5 packs of cigarettes.  This gives a rough and ready, serviceable estimate of the probable hazards of chronic methanol intake.



      The UK COT methanol review relies massively on an outdated and widely promoted paradigm which purports  methanol toxicity in humans mainly is due to the formation of formate (formic acid), which actually is so mild a toxin that WC Monte used it in his lab as salad dressing for his work lunches.  Thus, formaldehyde has been adroitly sidelined in recent decades as a possible major culprit:

      birth defects via methanol made by ADH1 enzyme into uncontrolled formaldehyde right inside cells of 20 tissues, in humans only, not by formate -- WC Monte gives 782 full text references at WhileScienceSleeps dot com: Rich Murray 2013.12.05

      methanol toxicity, not by formate, but by formaldehyde made inside human cells by ADH1 enzyme -- brief by Woodrow C. Monte, with lengthy references: Rich Murray 2013.05.24

      Vested interests have funded faulty research for decades to blame formate (formic acid) for the severe toxicity and acidosis of methanol in humans.

      Here is one brief review of several in "While Science Sleeps" 2012 January, by Prof. Woodrow C. Monte, Food Science and Nutrition, Arizona State University, retired 2004.

      Some of the references are in poorly legible pdfs, so I have copied them in full by hand into plain text.

      While Science Sleeps textbook, Chapter  6 "How Methanol Kills":

      free online archive of 782 mostly full text medical research references

      page 76:

      "The truth is that the other side [ methanol industry funded scientists ] of this issue has never proven beyond a reasonable doubt that formaldehyde is not involved in methanol poisoning.

      To the contrary, irrefutable evidence exists that the methyl alcohol from the aspartame molecule turns into formaldehyde [ right inside the cells ] within living tissue. 7

      Arguments from the dark side of this issue, refuting the outcome of this study, are meaningless gibberish. 40

      Many of the symptoms of acute methanol poisoning 3 are identical to those of acohol withdrawal 385 and not one of them has ever been associated with formic acid toxicity. 365

      Most convincing of all is that even though formic acid is found in the blood of those who consume large quantities of methanol, the levels are extremely variable -- but never high enough to inflict harm or to account for any of the major symptoms of methanol poisoning, including the increased acidity of the blood, that has been shown to be caused by lactic acid, not formic acid. 127, 205

      The older and more reliable research in this area has time and again established that the maximum amount of formic acid that can be produced from methanol in cases of poisoning is "without question" far too small to account for the acidity of the plasma in actual poisoning cases. 498

      As early as 1922 it was suggested correctly that our acidic Crazy Hawks [ vivid image for highly reactive hydrated formaldehyde, free floating inside human cells ] could be directly responsible for acidosis by neutralizing the amino acids of protein through the formation of methylene derivatives. 108, 443

      Professor Roe, the father of the ethanol cure for methanol poisoning, did the calculations to prove with certainty that nowhere near enough formic acid was produced during methanol poisoning to cause the recorded acidosis. 3

      [ Ethanol (ordinary drinking alcohol) is a potent antitdote that preoccupies ADH1 enzyme, which turns ethanol into acetaldehyde, which becomes harmless acetic acid (vinegar) -- only when all ethanol is gone from the blood, can the ADH1 enzyme then start turning methanol into formaldehyde right inside the cells of 20 human tissues, including the inner layers of brain blood vessels and the rods and cones of the retina. ]

      The fact is that every molecule of formic acid found in the bloodstream is a blessing, inasmuch as it accounts for one less molecule of formaldehyde [ inside cells ] attaching to an enzyme and causing problems.

      In a recent study of the biggest methanol outbreak ( 51 hospital admissions ), for which serum formate was measured, the patients were divided into three groups:

      Group I survived without problems,
      Group II survived with long term problems,
      and Group III died.

      The highest blood formate levels measured in each group, expressed in mmole/L, were
      Group I: 27
      Group II: 8
      and Group III: 6.

      This indicates that the higher the level of formate, the more likely the survival of the patient. 673

      Remember also that although it may be almost impossible to test for formaldehyde in a hospital setting, the odor of formalin on the breath or in the urine of poisoned individuals has been reported. 670

      This will be the last I have to say about the folly of blaming formic acid for the sins of formaldehyde."




      The next 5 posts give many studies that indicate the current methanol safety limit should be reduced 35 to 1,000 times:

      Kate S. Collison et al show prediabetic harm in gene expression in mice fed lifetime aspartame, MSG, trans fats -- reduce human aspartame ADI 1000 times: Rich Murray 2013.07.30

      aspartame harm in rat brain from 75 mg/kg gives human ADI 0.75 mg/kg, 53 times less than EU ADI 40 mg/kg, Ashok Iyyaswamy, SheelaDevi Rathinasamy, U. Madras 2012.08.03 free full text -- main methanol toxin is formaldehyde, not formate: Rich Murray 2013.06.01

      more lower aspartame and methanol ADIs from studies by RH Nair, SheelaDevi Rathinasamy, WC Monte, PS Jeganathan, A Namasivayam, Hazleton Labs, Searle Labs: Rich Murray 2013.06.01

      James McDonald to EFSA, outdated aspartame ADI gives methanol 35 times too high for human safety, ten minute talk at April 9 public sharing, Brussels: Rich Murray 2013.04.15

      California OEHHA sets methanol ingestion level 23 mg daily, same as from 1 can aspartame diet soda, 10 cigarettes, 3 tomatoes, or 4 cans green beans: Rich Murray 2013.07.03

      "However, the anticipated exposure to methanol from consumption of aspartame would not be considered an exposure within the meaning of Proposition 65 because aspartame is not listed under Proposition 65."

      [ Rich Murray: Many pregnant women drink one 12-oz can aspartame diet drink daily, with 200 mg aspartame that gives 11% methanol, 22 mg, which is just under the OEHHA limit of 23 mg daily.

      The smoke from 10 cigarettes gives 20 mg methanol, the same as from 3 full size fresh tomatoes, or 4 cans of unfresh green beans. ]

      smoke from pack cigarettes gives 40 mg methanol for 20 gr tobacco, 6 tobacco methanol papers, Carl Neuberg 1926-1939, Berlin -- so methanol formaldehyde toxicity paradigm is co-factor in 18 tobacco diseases -- WC Monte gives 23 references: Rich Murray 2013.03.29


      aspartame impairment of spatial cognition and insulin sensitivity in mice, focus on phenylalanine and aspartate [ methanol also crosses placenta into fetus, turning into teratogenic formaldehyde], Kate S. Collison et al, PLoS One 2012.04.03: Rich Murray 2012.04.29



      Evidence exists that autism results from exposure to pregnant women in the fourth week, since ADH1 levels are high in the Purkinje cells of the vermis in the cerebellum, while other plausible birth defects include spina bifida, premature birth, and Fetal Alcohol Spectrum Disorder:

      WC Monte finally got secret FDA memo 37 years after Searle Co. labs found birth defects in rabbits from aspartame (methanol, becomes formaldehyde via ADH1 enzyme within human cells) and its phenylalanine: Rich Murray 2012.06.02

      Fwd: Aspartame Submission from Prof. Woodrow C. Monte to EFSA:  While Science Sleeps: A Sweetener Kills 241 p  -- Ch 12   Autism and other Birth Defects  26 p -- 740 references full pdfs: Rich Murray 2011.11.03

      autism as a birth defect from epigenetic methylation by formaldehyde made from methanol by ADH1 enzyme inside Purkinje cells in vermis in cerebellum and in inner walls of brain blood vessels -- Prof. WC Monte paradigm: Rich Murray 2013.04.26

      CA Pardo autism brain autopsy findings in 2005 fit WC Monte paradigm -- methanol with blood half-life 3 hours is made by ADH1 enzyme into free floating formaldehyde in 20 defenseless human cells in 20 tissues: Rich Murray 2013.07.21

      Download Chapter 12 of the book "While Science Sleeps"
      "Autism and Other Birth Defects",
      with 100 free online full text references 




      Here are 4 posts on cancers:

      usual doses of aspartame proven to cause cancers, Michael F. Jacobson PhD, Director, Center for Science in the Public Interest -- also long 1985 statement: Rich Murray 2013.08.15

      highly competent, pithy analysis of aspartame cancer study by Eva S. Schernhammer at Harvard, William R. Ware, PhD, showing relevance of Woodrow C. Monte methanol-formaldehyde toxicity paradigm: Rich Murray 2012.12.03

      careful expert lifetime study on mice shows liver and lung cancers from aspartame, M Soffritti et al, Ramazzini Institute, Italy, checked by US National Toxicology Program experts, confirms many previous studies from 2001 on: Rich Murray 2011.02.27

      welcome to the WC Monte methanol formaldehyde toxicity paradigm via this treasury of studies -- depression, diabetes, retina harm, multiple sclerosis, cancer -- crisp Michele Bouchard 2001 review -- hangovers: Rich Murray 2013.02.21




      methanol/formaldehyde paradigm for multiple sclerosis, free full 56 page chapter 9 pdf, While Science Sleeps, 146 full text references online, Prof. Woodrow C. Monte: Rich Murray 2012.03.20

      Methyl alcohol ingestion as a model etiologic agent in multiple sclerosis, WC Monte, D Glanzman, C Johnston; Methanol induced neuropathology in the mammalian central nervous system, Woodrow C. Monte, Renee Ann Zeising, both reports 1989.12.04: Murray 2007.12.28 2012.05.01

      similar macular harm in multiple sclerosis as from formaldehyde made by ADH enzyme inside retina capillary walls from methanol, Prof. Woodrow C. Monte text "While Science Sleeps" 2012 Jan -- some quotes re retina harm: Rich Murray 2012.05.10




      The Woodrow C. Monte methanol/formaldehyde toxicity paradigm is that concentrations of ADH1 enzyme, well known to exist inside blood vessel wall cells in specific tissues, quickly turn methanol into formaldehyde inside the vessel cells, in humans only -- the highly reactive formaldehyde diffuses to penetrate adjacent tissue cells, binding to DNA, RNA, and proteins, attracting macrophages, which die, creating complex, expanding micro lesions, leading to many modern "diseases of civilization", Alzheimer's, arthritis, diabetes, multiple sclerosis, lupus -- as well as later cancers -- also serious birth defects in the fetal brain in the fourth week of pregnancy, spinal bifida and autism.

      Aspartame is 11% methanol, 22 mg per can of diet drink -- similar levels of methanol come from wood and cigarette smoke, heated and canned fruits juices vegetables, fermented and smoked foods, some wines and liquors, vehicle fuels, many cleaners and solvents, chemical medical autopsy mortuary facilities, heated wood in particleboard and paper factories, and more.

      WC Monte submits robust evidence for multiple sclerosis, which he concludes proves methanol to be the proximate toxic cause, since ADH1 enzyme is within the cells of the inner linings of brain blood vessels, the Purkinje cells of the vermis of the cerebellum, and rods and cones of the retina -- ADH1 quickly turns methanol into free floating formaldehyde within these cells, disrupting the blood brain barrier...


      free full text, 245 page EFSA draft report on methanol toxicity 2013.01.08 ]

      The public EFSA session on aspartame safety on April 9 for 5 hours included an audience of about 50 experts and 10-20 ESFA staff in Brussels.
      The release of the final EFSA review on aspartame safety will be delayed from April 15 to early December, 2013.
      Extremely cogent multiple lines of robust evidence were briefly described that strongly support the methanol formaldehyde toxicity paradigm of Prof. Woodrow C. Monte, Prof. Food Science and Nutrition, Arizona State University, retired 2004 -- supported by an online archive of 782 free full text medical research references at www.WhileScienceSleeps.com .

      It is clear that methanol is far more dangerous for chronic low level exposures than realized since 1890.

      Major sources include the smoke from a pack of cigarettes, 40 mg methanol,the same as from 2 cans aspartame diet drink.  It now seems likely that most cigarette diseases are actually methanol toxicity...

      Methanol stays in the blood with a half-life of 3 hours, reaching every part of the body and the fetus with the bloodstream, and readily entering all cells.

      Humans are uniquely vulnerable to methanol formaldehyde toxicity, as they lack a functioning catalase enzyme system, that in all other creatures serves to protect each cell against the rapid conversion of methanol into free floating formaldehyde right inside the cells of 20 specific tissues that have high levels of ADH1 enzyme.

      The effects are used to good advantage in embalming and disinfection, as formaldehyde immediately bonds to and impairs DNA, RNA, and proteins, permanently disrupting cell biochemistry, cell by cell, as long as methanol is ingested -- leading to 20 specific chronic modern novel "diseases of civilization", that progress slowly and erratically, according to the ingestion of methanol from a variety of modern sources:

      smoke from cigarettes, wood, and peat;

      since 1983, aspartame, including from most chewing gums;

      fresh tomatoes and black currants;

      unfresh fruits juices vegetables cut up and preserved wet at room temperature in sealed cans jars plastic containers;

      jams jellies marmalades;

      smoked fermented spoiled foods;

      many dark wines and liquors;

      work at paper and wood factories, mortuaries, medical and chemical facilities;


      Research since 2012 specifically shows the presence of formaldehyde bonded to cellular macromolecules inside cells after methanol ingestion -- the paradigm will be confirmed in detail very quickly, as science exponentially explores this simple breakthrough.

      This presents the world food industry with an unprecedented opportunity to serve the huge public good by collaborating vigorously to eliminate all methanol exposures from foods and beverages. The Net guarantees that the news and evidence will spread explosively everywhere.


      Paul Thomas MD Pediatrics and Integrative Medicine, Portland OR, praises "While Science Sleeps" at Amazon.com -- WC Monte paradigm of methanol formaldehyde toxicity via ADH1 enzyme in 20 human tissues, including fetus: Rich Murray 2013.04.03


      Prof. Resia Pretorius letter re aspartame to EJCN cites Prof. Woodrow C. Monte "While Science Sleeps" text, re methanol/formaldehyde toxicity paradigm: Rich Murray 2012.05.21


      Aspartame: The hidden danger [methanol/formaldehyde] in our midst and how it kills us, 12 page review of While Science Sleeps text (Woodrow C Monte), International Health News, whole June issue, Editor: William R Ware PhD: Rich Murray 2012.06.08




      confirms WC Monte paradigm: ingested methanol becomes toxic formaldehyde-induced hydroxymethyl DNA adducts in all tissues in rats, sensitive C13 test, Kun Lu, James A Swenberg, UNC Chapel Hill 2011.12.08 Toxicol Sci: Rich Murray 2013.01.11

      [ comments by Rich Murray are in square brackets. ]

      you can give EFSA 1 page public comments -- EFSA panel says aspartame
      safe, takes public comments until 2013.02.15, 245 page draft report,
      2.9 MB pdf: Rich Murray 2013.01.08

      free full text, 245 page EFSA draft report

      [ line number in EFSA draft report ]
      "4063  In a recent study (Lu et al., 2012) formaldehyde hydroxymethyl DNA adducts have been measured after administration of labelled [13CD4]-methanol to rats (500 and 2000 mg/kg bw/day for 5 days) in multiple tissues in a dose dependent manner.

      This finding is in line with the known metabolism of methanol."

      [ The half life of methanol in human blood is about 3 hours. Actually, the huge oral dose is enough to saturate the rats' catalase defense system, resulting in their ADH1 making methanol into toxic formaldehyde in many tissues, whereas in humans only, whose defective catalase enzyme fails to safely metabolize formaldehyde inside the many protective peroxisomes in every cell, the ADH1 enzyme, in high levels in 19 specific tissues, quickly turns bloodborne methanol into uncontrolled free floating highly toxic formaldehyde inside cells.  ]

      [ 3 references in EFSA draft report 2013.01.08 ]

      "6131
      Lu K, Collins LB, Ru H, Bermudez E and Swenberg JA, 2010.
      Distribution of DNA adducts caused inhaled formaldehyde is consistent with induction of nasal carcinoma but not leukemia.
      Toxicological Sciences, 116, 441–451.

      6134
      Lu K, Moeller B, Doyle-Eisele M, McDonald J and Swenberg JA, 2011.
      Molecular dosimetry of N2-hydroxymethyl-dG DNA adducts in rats exposed to formaldehyde.
      Chemical Research in Toxicology, 24, 159–161.

      6137
      Lu K, Gul H, Upton PB, Moeller BC and Swenberg JA, 2012.
      Formation of hydroxymethyl DNA adducts in rats orally exposed to stable isotope labeled methanol.
      Toxicological Sciences, 126, 28-38."


      abstract

      free full text


      [ quoted from abstract of above reference ]
      "However, formaldehyde-induced DNA adducts arising from the metabolism
      of methanol have not been reported previously, largely due to the
      absence of suitable DNA biomarkers and the inability to differentiate
      what was due to methanol compared with the substantial background of
      endogenous formaldehyde.

      [ The human body normally safely processes about 50 grams of "endogenous" formaldehyde in carefully orchestrated biochemical reactions, whereas uncontrolled, highly toxic "exogenous" formaldehyde is formed from ingested methanol inside cells via the ADH1 enzyme, located in high levels in 19 specific human tissues. ]

      Recently, we developed a unique approach combining highly sensitive
      liquid chromatography-mass spectrometry methods and exposure to stable
      isotope labeled chemicals to simultaneously quantify
      formaldehyde-specific endogenous and exogenous DNA adducts.

      In this study, rats were exposed daily to 500 or 2000 mg/kg
      [13CD4]-methanol by gavage for 5 days.

      [ The methanol (CH3OH) was labeled by  molecular weight changes by substituting carbon 13 for ordinary carbon 12 and deuterium for hydrogen. ]

      Our data demonstrate that labeled formaldehyde arising from
      [13CD4]-methanol induced hydroxymethyl DNA adducts in multiple tissues
      in a dose-dependent manner.

      The results also demonstrated that the number of exogenous DNA adducts
      was lower than the number of endogenous hydroxymethyl DNA adducts in
      all tissues of rats administered 500 mg/kg per day for 5 days,
      a lethal dose to humans, even after incorporating an average factor of 4
      for reduced metabolism due to isotope effects of deuterium-labeled
      methanol into account."

      [ They swamped the rats' catalase defense with a huge dose of methanol,
      so that ADH1 made it into free floating formaldehyde within cells,
      which immediately made exogenous hydrooxymethyl DNA adducts in all
      tissues with high levels of ADH1 enzyme. ]

      Toxicol Sci. 2012 Mar;126(1):28-38.
      doi: 10.1093/toxsci/kfr328.
      Epub 2011 Dec 8.
      Formation of hydroxymethyl DNA adducts in rats orally exposed to
      stable isotope labeled methanol.
      Lu K,
      Gul H,
      Upton PB,
      Moeller BC,
      Swenberg JA.
      Department of Environmental Sciences and Engineering,
      University of North Carolina at Chapel Hill,
      Chapel Hill, North Carolina 27599, USA.

      Abstract

      Methanol is a large volume industrial chemical and widely used solvent
      and fuel additive.

      Methanol's well known toxicity and use in a wide spectrum of
      applications has raised long-standing environmental issues over its
      safety, including its carcinogenicity.

      Methanol has not been listed as a carcinogen by any regulatory agency;
      however, there are debates about its carcinogenic potential.

      Formaldehyde, a metabolite of methanol, has been proposed to be
      responsible for the carcinogenesis of methanol.

      Formaldehyde is a known carcinogen and actively targets DNA and
      protein, causing diverse DNA and protein damage.

      However, formaldehyde-induced DNA adducts arising from the metabolism
      of methanol have not been reported previously, largely due to the
      absence of suitable DNA biomarkers and the inability to differentiate
      what was due to methanol compared with the substantial background of
      endogenous formaldehyde.

      Recently, we developed a unique approach combining highly sensitive
      liquid chromatography-mass spectrometry methods and exposure to stable
      isotope labeled chemicals to simultaneously quantify
      formaldehyde-specific endogenous and exogenous DNA adducts.

      In this study, rats were exposed daily to 500 or 2000 mg/kg
      [13CD4]-methanol by gavage for 5 days.

      [ The methanol (CH3OH) was labeled by  molecular weight changes by substituting carbon 13 for ordinary carbon 12 and deuterium for hydrogen. ]

      Our data demonstrate that labeled formaldehyde arising from
      [13CD4]-methanol induced hydroxymethyl DNA adducts in multiple tissues
      in a dose-dependent manner.

      The results also demonstrated that the number of exogenous DNA adducts
      was lower than the number of endogenous hydroxymethyl DNA adducts in
      all tissues of rats administered 500 mg/kg per day for 5 days,
      a lethal dose to humans, even after incorporating an average factor of 4
      for reduced metabolism due to isotope effects of deuterium-labeled
      methanol into account.

      PMID: 22157354
      [PubMed - indexed for MEDLINE]
      PMCID:
      PMC3289495 [Available on 2013/3/1]



      The most recent version of this article was published on 2012-02-28




      comment 1 on 5.1 methanol metabolism, EFSA aspartame draft : Rich Murray 2013.01.14


      [ 3796 characters]
      4018 5.1. Absorption, distribution, metabolism and excretion of methanol

      "4063  In a recent study (Lu et al., 2012) formaldehyde hydroxymethyl DNA adducts have been measured after administration of labelled [13CD4]-methanol to rats (500 and 2000 mg/kg bw/day for 5 days) in multiple tissues in a dose dependent manner.

      This finding is in line with the known metabolism of methanol."

      [ reference in EFSA draft report ]
      line 6137
      Lu K, Gul H, Upton PB, Moeller BC and Swenberg JA, 2012.
      Formation of hydroxymethyl DNA adducts in rats orally exposed to stable isotope labeled methanol.
      Toxicological Sciences, 126, 28-38."

      free full text

      Abstract

      Methanol is a large volume industrial chemical and widely used solvent and fuel additive.
      Methanol's well known toxicity and use in a wide spectrum of applications has raised long-standing environmental issues over its safety, including its carcinogenicity.
      Methanol has not been listed as a carcinogen by any regulatory agency; however, there are debates about its carcinogenic potential.
      Formaldehyde, a metabolite of methanol, has been proposed to be responsible for the carcinogenesis of methanol.
      Formaldehyde is a known carcinogen and actively targets DNA and protein, causing diverse DNA and protein damage.
      However, formaldehyde-induced DNA adducts arising from the metabolism of methanol have not been reported previously, largely due to the absence of suitable DNA biomarkers and the inability to differentiate what was due to methanol compared with the substantial background of endogenous formaldehyde.

      Recently, we developed a unique approach combining highly sensitive liquid chromatography-mass spectrometry methods and exposure to stable isotope labeled chemicals to simultaneously quantify formaldehyde-specific endogenous and exogenous DNA adducts.

      In this study, rats were exposed daily to 500 or 2000 mg/kg [13CD4]-methanol by gavage for 5 days.

      Our data demonstrate that labeled formaldehyde arising from [13CD4]-methanol induced hydroxymethyl DNA adducts in multiple tissues in a dose-dependent manner...

      PMID: 22157354 [PubMed - indexed for MEDLINE]
      PMCID: PMC3289495 [Available on 2013/3/1]

      The most recent version of this article was published on 2012-02-28

      Kim J, Mastronardi F, Wood D, Lubman D, Zand R, Moscarello M.
      Multiple Sclerosis: An important role for post-translational modifications
      of myelin basic protein in pathogenesis.
      Molecular & Cellular Proteomics 2003;2(7):453-62.

      "Myelin basic protein (MBP) represents a candidate autoantigen in
      multiple sclerosis (MS). We isolated MBP from normal and MS human
      white matter and purified six components (charge isomers) to compare
      the post-translational modifications on each. The sites and extent of
      methylation, deimination, and phosphorylation were documented for all
      tryptic peptides by mass spectrometry. We found that mono and
      dimethylated arginine 107 was increased in MS samples;..."

      Prof. Woodrow C. Monte states that only acidic hydrated formaldehyde
      from methanol via the ADH1 enzyme in brain blood vessels can cause
      this striking methylation, in "While Science Sleeps" textbook, 2012
      January, pages 133-6, in free Chapter 9 "Multiple Sclerosis", at
      WhileScienceSleeps.com, along with free online archive of 745 mostly
      full text medical research references.

      Both a litre aspartame diet drink and the smoke from a pack of
      cigarettes give 60 mg methanol, 6 times the usual body burden, which
      has a blood half-life of 3 hours, reaching all parts of the body and
      fetus, while being made into formaldehyde by ADH1 enzyme right inside
      the cells of 19 specific human tissues, including brain blood vessels.
      [ end of comment 1 ]





      #6 diabetes 2 risk high for 2 cans aspartame diet drink weekly 14
      years 66K women study, Guy Fagherazzi et al AJCN 2013 Jan -- methanol
      (cigarettes, aspartame) formed into formaldehyde inside cells in
      pancreas by ADH1 enzyme, WC Monte paradigm: Rich Murray 2013.02.13




      #4 methanol formaldehyde toxicity in alcohol withdrawal syndrome study on closed hospital ward in 1969, Edward Majchrowicz and Jack H. Mendelson -- fits WC Monte paradigm: comment on EFSA draft aspartame review: Rich Murray 2013.02.02

      [ 3800 characters ] line 937
      In March 2011, the UK COT (UK Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment) issued a statement on effects of chronic dietary exposure to methanol. The COT was asked to consider the effects of chronic oral methanol exposure in the light of consumer concerns that methanol arising from the breakdown of the sweetener aspartame could be harmful (COT, 2011).

      In its statement, the COT concluded that exposure to methanol at the levels found in the diet (dietary methanol has been estimated to be up to 1 g/day), both naturally occurring and from currently permitted levels of aspartame, would not be expected to result in adverse effects.

      line 5826
      COT (UK Committee on toxicity of chemicals in food, consumer products and the environment),
      2011. COT Statement on the effects of chronic dietary exposure to methanol.
      Available at:
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