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Ramazzini Institute (Italy) lifetime study with 1800 rats shows aspartame at human use levels causes cancer (methanol, formaldehyde, formic acid), M Soffritti and F Belpoggi: Felicity Lawrence, The Guardian (UK): Murray 2005.07.15

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  • Rich Murray
    ************************************************************** http://groups.yahoo.com/group/aspartameNM/message/1185 Ramazzini Institute (Italy) lifetime
    Message 1 of 1 , Jul 15, 2005
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      http://groups.yahoo.com/group/aspartameNM/message/1185
      Ramazzini Institute (Italy) lifetime study with 1800 rats shows aspartame at
      human use levels causes cancer (methanol, formaldehyde, formic acid), M
      Soffritti and F Belpoggi: Felicity Lawrence, The Guardian (UK): Murray
      2005.07.15

      Rich Murray, MA Room For All rmforall@... 505-501-2298
      1943 Otowi Road Santa Fe, New Mexico 87505 USA
      http://groups.yahoo.com/group/aspartameNM/messages
      group with 187 members, 1,185 posts in a public, searchable archive


      Results of long term carcinogenesis bioassasy on aspartame administered to
      Sprague-Dawley rats
      Fiorella Belpoggi, Italy [ female ] crcfr@...

      http://www.guardian.co.uk/uk_news/story/0,3604,1528885,00.html

      Fresh fears raised about aspartame

      Manufacturers dispute study into lab rats fed sweetener

      Felicity Lawrence, consumer affairs correspondent
      Friday July 15, 2005 The Guardian (UK)

      The European Food Safety Authority is reviewing "as a matter of high
      priority" the results of a large new study into aspartame, the artificial
      sweetener consumed by millions of people worldwide and used in more than
      6,000 food and drink products.

      Researchers at the Ramazzini Institute for cancer research in Italy say
      their study shows that aspartame causes lymphomas and leukaemia in female
      laboratory animals "at doses very close to the acceptable daily intake for
      humans".

      The authors of the study also say that while rats fed aspartame ate less
      food, there was no difference in body weight between treated and untreated
      animals.

      One of the largest manufacturers of aspartame, the Japanese multinational
      Ajinomoto said the allegations made by the Italian study were "not
      consistent with the extensive body of scientific research which already
      exists on aspartame".
      It questioned the methods used and the record of the institute.
      It pointed to four previous studies into the carcinogenicity of aspartame
      that had found no relationship between aspartame and any form of cancer.
      It added that aspartame broke down in the body into the building blocks of
      protein that occur widely in the rest of food.

      It also helped people reduce their calorie intake. This contribution to
      cutting obesity helped to prevent cancer, a spokesman said.

      The Ramazzini Institute has sent its first results to the European Food
      Safety Authority.

      EFSA confirmed yesterday that it would be asking its expert scientific panel
      on food additives to review the results "as a matter of high priority, in
      the context of the previous extensive safety data available on aspartame".

      EFSA added that until that review had taken place it did not have a basis
      for recommending that consumers change their diet in respect of aspartame.

      Although it had been presented with an outline of the findings by the
      institute in June, it is still waiting for the full pathology reports from
      the researchers.
      The review will also take into account all the other studies and data
      available.
      "This will probably take several months," an EFSA statement said.

      The institute said the full data would be published in six weeks' time.

      Aspartame is widely used to sweeten chewing gum, soft drinks, yoghurts and
      desserts and other low-calorie foods, and medicines including syrups and
      antibiotics for children.

      Aspartame has been authorised for use in foods for a long time in many
      countries but has "a controversial history", according to EFSA.
      Since its approval, the safety of aspartame and its breakdown products has
      been widely discussed in the press and among scientists.
      "Up to now aspartame has been considered safe, based on the studies
      available."

      The new study was conducted on 1,800 rats during their full lifespan.
      Six different dose levels were tested against a control group.
      The institute said the study, which is to appear in its own publication, the
      European Journal of Oncology, had been peer-reviewed by seven international
      experts "in anticipation of controversy".

      Ajinomoto said it welcomed the decision by EFSA to review the claim made by
      the Ramazzini Institute objectively.
      **************************************************************

      http://news.bbc.co.uk/2/hi/health/4683371.stm

      Sweetener 'linked' to leukaemias

      Aspartame is used to sweeten low calorie soft drinks

      Fresh doubts about the safety of an artificial sweetener have been raised by
      Italian scientists who have linked its use to leukaemias in rodents.

      Aspartame is 200 times sweeter than sugar and is used throughout the world
      in low-calorie drinks and foods.

      Regulators say existing studies show it is safe, but will look at the
      European Journal of Clinical Oncology study.

      But they said it was unlikely that the sweetener was harmful to humans to
      the same extent as in rats.

      Concerns have been raised about the aspartame in the past, but an analysis
      of 500 papers by UK regulators in 2002 concluded there was no threat to
      consumers.

      The Food Standards Agency said: "The European Food Safety Authority intends
      to undertake an urgent assessment of this study to establish whether there
      are any implications for human health.

      "We will study EFSA's opinion carefully and consider what, if any, action
      may be required."

      Dr Elaine Vickers, cancer information officer at Cancer Research UK, said:
      "If a risk to humans does exist, it will almost certainly be very small.

      "However, we welcome the news that the EFSA will undertake an urgent
      assessment of this work."

      The study

      Dr Morando Soffritti and colleagues at the Cancer Research Centre in Bologna
      fed eight-week-old rats varying concentrations of aspartame. [ for two
      years ]

      Compared with control rats given no sweetener, many of the female rats in
      the experiment developed lymphomas or leukaemias -- the risk increasing with
      the dose of aspartame. [ The rats were studied until natural death. ]

      The researchers say their study raises concerns about the levels of
      aspartame to which humans can be exposed and, therefore, "urgent
      re-examination" of aspartame's safety is needed, "especially to protect
      children".

      The existing European Food Safety Authority safety assessment for aspartame
      led to the setting of an Acceptable Daily Intake, or ADI.

      This is an estimate of the amount of an additive that could be routinely
      consumed every day over a lifetime with no appreciable health risk.

      'Safe' intake

      Aspartame's ADI is set at 40 milligrams per kilogram of body weight. This is
      equivalent to 2,800 milligrams for an average British adult.

      For an average three-year-old child the amount is of the order of 600
      milligrams.

      An adult would have to consume 14 cans of a sugar-free drink every day
      before reaching the ADI, assuming the sweetener was used in the drink at the
      maximum permitted level.

      In practice, most drinks use aspartame in combination with other sweeteners
      so that the level is considerably lower, says the FSA.

      Previous work by the former Ministry of Agriculture, Fisheries and Food and
      the Department of Health showed that aspartame intakes were considerably
      below the recommended maximum level, even among children and diabetics who
      consume large quantities of sugar-free drinks.
      ***************************************************************

      http://groups.yahoo.com/group/aspartameNM/message/1045
      http://www.holisticmed.com/aspartame/scf2002-response.htm
      Mark Gold exhaustively critiques European Commission Scientific
      Committee on Food re aspartame ( 2002.12.04 ): 59 pages, 230 references
      ***************************************************************

      http://www.collegiumramazzini.org/ram1.htm Collegium Ramazzini

      http://www.ramazzini.it/living2005/scientificsession.asp

      3rd International Scientific Conference: Framing the Future in Light of the
      Past:
      Living in a Chemical World Bologna, Italy 2005 September 18-21

      I. IDENTIFYING AND PREVENTING HAZARDS
      IN THE ENVIRONMENT AND AT WORK
      II. REDUCING AND MANAGING RISK IN HIGH HAZARD SECTORS
      III. TOOLS AND STRATEGIES TO REDUCE RISK: APPLYING SCIENCE TO ACHIEVE
      PREVENTION

      ROUNDTABLE SESSIONS

      Long Term Carcinogenesis Bioassays and Other Testing Strategies
      Co-chairs: James Huff, USA & Morando Soffritti, Italy

      Results of long term carcinogenesis bioassasy on aspartame administered to
      Sprague-Dawley rats
      Fiorella Belpoggi, Italy [ female ] crcfr@...

      Please contact
      Kathryn Knowles, Fondazione Ramazzini living2005@...
      (+39) 051 6640460
      **************************************************************


      Fully 11% of aspartame is methanol-- 1,120 mg aspartame in 2 L diet soda,
      almost six 12-oz cans, gives 123 mg methanol (wood alcohol). If 30% of
      the methanol is turned into formaldehyde, the amount of formaldehyde is 18
      times the USA EPA limit for daily formaldehyde in drinking water, 2 mg in 2
      L water.

      http://groups.yahoo.com/group/aspartameNM/message/835
      ATSDR: EPA limit 1 ppm formaldehyde in drinking water July 1999:
      Murray 2002.05.30 rmforall

      Aspartame is made of phenylalanine (50% by weight) and aspartic acid (39%),
      both ordinary amino acids, bound loosely together by methanol (wood alcohol,
      11%). The readily released methanol from aspartame is within hours turned
      by the liver into formaldehyde and then formic acid, both potent, cumulative
      toxins.


      http://groups.yahoo.com/group/aspartameNM/message/1182
      Joining together: short review: research on aspartame (methanol,
      formaldehyde, formic acid) toxicity: Murray 2005.07.08 rmforall

      http://groups.yahoo.com/group/aspartameNM/message/1071
      research on aspartame (methanol, formaldehyde, formic acid) toxicity: Murray
      2004.04.29 rmforall

      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 2005.04.02 rmforall

      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/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

      http://groups.yahoo.com/group/aspartameNM/message/1067
      eyelid contact dermatitis by formaldehyde from aspartame, AM Hill & DV
      Belsito, Nov 2003: Murray 2004.03.30 rmforall

      Thrasher (2001): "The major difference is that the Japanese demonstrated
      the incorporation of FA and its metabolites into the placenta and fetus.
      The quantity of radioactivity remaining in maternal and fetal tissues
      at 48 hours was 26.9% of the administered dose." [ Ref. 14-16 ]

      Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
      Embryo toxicity and teratogenicity of formaldehyde. [100 references]
      Thrasher JD, Kilburn KH. toxicology@...
      Sam-1 Trust, Alto, New Mexico, USA.
      http://www.drthrasher.org/formaldehyde_embryo_toxicity.html full text

      http://groups.yahoo.com/group/aspartameNM/message/939
      aspartame (aspartic acid, phenylalanine) binding to DNA:
      Karikas July 1998: Murray 2003.01.05 rmforall
      Karikas GA, Schulpis KH, Reclos GJ, Kokotos G
      Measurement of molecular interaction of aspartame and
      its metabolites with DNA. Clin Biochem 1998 Jul; 31(5): 405-7.
      Dept. of Chemistry, University of Athens, Greece
      http://www.chem.uoa.gr gkokotos@...
      "K.H. Schulpis" <inchildh@...> "G.J. Reclos" reklos@...

      http://groups.yahoo.com/group/aspartameNM/message/1052
      DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol 98 mg/L
      [ becomes formaldehyde in body ]: EU Scientific Committee on Foods
      2001.07.12: Murray 2004.01.22 rmforall


      An intripid and much published team in Japan has found DNA damage
      in 8 tissues from single non-lethal doses of aspartame (near-significant
      high levels of DNA damage in 5 tissues) and many other additives in groups
      of just 4 mice:

      Mutat Res 2002 Aug 26; 519(1-2): 103-19
      The comet assay with 8 mouse organs: results with 39 currently used food
      additives.
      Sasaki YF, Kawaguchi S, Kamaya A, Ohshita M, Kabasawa K, Iwama K,
      Taniguchi K, Tsuda S.
      Laboratory of Genotoxicity, Faculty of Chemical and Biological
      Engineering, Hachinohe National College of Technology,
      Tamonoki Uwanotai 16-1, Aomori 039-1192, Japan.
      yfsasaki-c@... s.tsuda@...

      We determined the genotoxicity of 39 chemicals currently in use as food
      additives.
      They fell into six categories-dyes, color fixatives and
      preservatives, preservatives, antioxidants, fungicides, and sweeteners.

      We tested groups of four male ddY mice once orally with each additive at
      up to 0.5xLD(50) or the limit dose (2000mg/kg) and performed the comet
      assay on the glandular stomach, colon, liver, kidney, urinary bladder, lung,
      brain, and bone marrow 3 and 24 h after treatment.

      Of all the additives, dyes were the most genotoxic.
      Amaranth, Allura Red, New Coccine, Tartrazine, Erythrosine, Phloxine, and
      Rose Bengal induced dose-related DNA damage
      in the glandular stomach, colon and/or urinary bladder.
      All seven dyes induced DNA damage in the gastrointestinal organs at a low
      dose (10 or 100mg/kg).

      Among them, Amaranth, Allura Red, New Coccine, and Tartrazine induced
      DNA damage in the colon at close to the acceptable daily intakes (ADIs).

      Two antioxidants (butylated hydroxyanisole (BHA) and butylated
      hydroxytoluene (BHT)), three fungicides (biphenyl, sodium
      o-phenylphenol, and thiabendazole), and four sweeteners (sodium
      cyclamate, saccharin, sodium saccharin, and sucralose) also induced DNA
      damage in gastrointestinal organs.

      Based on these results, we believe that more extensive assessment of
      food additives in current use is warranted. PMID: 12160896

      http://groups.yahoo.com/group/aspartameNM/message/934
      24 recent formaldehyde toxicity [Comet assay] reports:
      Murray 2002.12.31 rmforall

      http://groups.yahoo.com/group/aspartameNM/message/935
      Comet assay finds DNA damage from sucralose, cyclamate, saccharin in
      mice: Sasaki YF & Tsuda S Aug 2002: Murray 2003.01.01 rmforall
      [ Also borderline evidence, in this pilot study of 39 food additives,
      using test groups of 4 mice, for DNA damage from for stomach, colon,
      liver, bladder, and lung 3 hr after oral dose of 2000 mg/kg aspartame--
      a very high dose.]

      http://groups.yahoo.com/group/aspartameNM/message/961
      genotoxins, Comet assay in mice: Ace-K, stevia fine; aspartame poor;
      sucralose, cyclamate, saccharin bad: Y.F. Sasaki Aug 2002:
      Murray 2003.01.27 rmforall [A detailed look at the data] ]



      Clearly, Europe has placed the issue of aspartame toxicity on the table
      as a legitimate, urgent issue for evidence-based public discussion.

      Perhaps this shift in the climate of opinion is due to:
      European Ramazzini Foundation, led by Morando Soffritti, MD.
      crcfr@... Cancer Research Center, European Ramazzini Foundation for
      Oncology and Environmental Sciences, Bentivoglio Castle, 40010
      Bentivoglio (BO), Italy. +39-051-6640460 fax +39-051-6640223

      Annuals of the New York Academy of Science. 2002 Dec; Vol. 982:

      The RF research program was started in 1966 by the eminent Cesare
      Maltoni, (1930-2001):
      p. 6 "Maltoni was known for his meticulous and carefully documented
      experiments.
      He studied 198 chemicals and agents and conducted 394 separate experiments
      using 138,281 animals.
      Of the 135 agents studied,
      68.9% were found to be carcinogenic,
      5.92% showed borderline carcinogenicity,
      and 25.18% were found to be noncarcinogenic in the animals tested."
      Often, the hundreds to thousands of rats in each study were exposed daily
      for two years and then thoroughly examined for cancers after their later
      natural deaths.

      http://www.nyas.org/books/vols/v982.html
      Annals of the New York Academy of Sciences
      Carcinogenesis Bioassays and Protecting Public Health:
      Commemorating the Lifework of Cesare Maltoni and Colleagues
      Edited by Myron A. Mehlman (Collegium Ramazzini, Princeton, NJ);
      [Dept. of Environmental Medicine, The Mount Sinai Medical Center, New
      York City, mehlman@... 609-683-4750]
      Eula Bingham (University of Cincinnati College of Medicine, Cincinnati, OH);
      Philip J. Landrigan (Mount Sinai School of Medicine, New York, NY);
      Morando Soffritti, Fiorella Belpoggi, European Ramazzini Foundation;
      Ronald L. Melnick, National Institute of Environmental Health Sciences,
      Research Triangle Park, NC

      Proceedings of an April 29-30, 2002 Academy conference.
      Volume 982 ISBN 1-57331-406-4
      231 pages 14 papers 0 posters Price: $135.00
      Member Price *: $15.00 December 2002

      Long-term experimental carcinogenesis studies are the cornerstone of
      human health protection and risk assessment for drugs and chemicals.
      Great contributions to the development of bioassay methodology and the
      understanding of the mechanisms of carcinogenesis were made by Professor
      Cesare Maltoni at the European Foundation of Oncology and Environmental
      Sciences "B. Ramazzini," Bologna, Italy.
      This volume is based on a conference that was held on the first anniversary
      of Professor Maltoni's death to honor him and to celebrate the work on
      carcinogenesis bioassays carried out at the Ramazzini Foundation Cancer
      Research Center in Italy and at the National Toxicology Program, NIEHS, in
      the United States.
      Papers include reviews of previously unreported findings and discussion
      of the continued utility of such studies for the protection of public
      health.
      Full text of volume 837 and forward is available at Annals
      Online to Academy Members at Members Online and to subscribing
      libraries. New York Academy of Sciences 2 East 63rd St., NY, NY 10021

      "(3) formaldehyde may produce lymphomas and leukemias..."

      Ann N Y Acad Sci. 2002 Dec; 982: 26-45.
      Ramazzini Foundation cancer program: history and major projects,
      life-span carcinogenicity bioassay design, chemicals studied, and
      results.
      Soffritti M, Belpoggi F, Minardi F, Maltoni C.
      Cancer Research Center, European Ramazzini Foundation for Oncology and
      Environmental Sciences, Bologna, Italy. crcfr@...

      The Ramazzini Foundation research program was started over thirty years
      ago. The features of this program are:
      (1) systematic and integrated project design;
      (2) consistency over time;
      (3) homogeneity of approach: key members of the team remain unchanged;
      and (4) choice to work on new frontiers of scientific research.
      The program centers mainly on three projects:
      Project 1: experimental carcinogenicity bioassays;
      Project 2: experimental anticarcinogenesis assays to identify factors
      and active principles (compounds) capable of opposing the onset of
      tumors while being suitable for preventive/chemopreventive intervention;
      Project 3: epidemiological studies, both descriptive and analytical, on
      tumor incidence and mortality in persons professionally and
      environmentally exposed to industrial carcinogenic risks.
      The project involving experimental carcinogenicity bioassays for the
      identification of exogenous carcinogens (environmental and industrial
      above all) began in 1966.
      This project has included 398 experimental bioassays on 200
      compounds/agents using some 148,000 animals monitored until their
      spontaneous death.
      Among the studies already concluded, 47 agents have shown "clear
      evidence" of carcinogenicity.
      The results have demonstrated for the first time that
      (1) vinyl chloride can cause liver angiosarcoma as well as other tumors;
      (2) benzene is carcinogenic in experimental animals for various tissues
      and organs;
      (3) formaldehyde may produce lymphomas and leukemias; and
      (4) methyl-tert-butyl ether (MTBE), the most common oxygenated additive
      used in gasolines, can cause lymphomas/leukemias.
      Many of the results achieved have led to the introduction of norms and
      measures of primary prevention.
      Publication Types: Historical Article PMID: 12562627



      p. 48 "The sweetening agent aspartame hydrolyzes in the gastrointestinal
      tract to become free methyl alcohol. (25)"
      "(25) Medinsky MA & Dorman DC. 1994; Assessing risks of low-level
      methanol exposure. CIIT Act. 14: 1-7.
      (30) Monte WC. 1984; Aspartame, methanol and the public health.
      Journal Applied Nutrition. Vol 36: 42-54."

      Ann N Y Acad Sci. 2002 Dec; 982: 46-69.
      Results of long-term experimental studies on the carcinogenicity of
      methyl alcohol and ethyl alcohol in rats.
      Soffritti M, Belpoggi F, Cevolani D, Guarino M, Padovani M, Maltoni C.
      Cancer Research Center, European Ramazzini Foundation for Oncology and
      Environmental Sciences, Bologna, Italy. crcfr@...

      Methyl alcohol was administered in drinking water supplied ad libitum at
      doses of 20,000, 5,000, 500, or 0 ppm to groups of male and female
      Sprague-Dawley rats 8 weeks old at the start of the experiment.
      Animals were kept under observation until spontaneous death.
      Ethyl alcohol was administered by ingestion in drinking water at a
      concentration of 10% or 0% supplied ad libitum to groups of male and
      female Sprague-Dawley rats; breeders and offspring were included in the
      experiment.
      Treatment started at 39 weeks of age (breeders), 7 days before mating,
      or from embryo life (offspring) and lasted until their spontaneous death.
      Under tested experimental conditions, methyl alcohol and ethyl alcohol
      were demonstrated to be carcinogenic for various organs and tissues.
      They must also be considered multipotential carcinogenic agents.
      In addition to causing other tumors, ethyl alcohol induced malignant
      tumors of the oral cavity, tongue, and lips.
      These sites have been shown to be target organs in man by epidemiologic
      studies. Publication Types: Review Review, Tutorial PMID: 12562628



      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 & Dorman 1994]"

      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@...

      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: [ comment made spring, 2003 ]

      p. 29-32 Table 1: The Ramazzinni Foundation Cancer Program
      Project of [200] 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/conference/conf_02_0429.html
      Soffritti said that Coca-Cola showed no carcinogenicity.
      *************************************************************

      http://www.annalsnyas.org/content/vol982/issue1/ Table of Contents
      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@...
      MORANDO SOFFRITTI, FIORELLA BELPOGGI, LUCA LAMBERTIN, MICHELINA LAURIOLA,
      MICHELA PADOVANI, and CESARE MALTONI

      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




      Ann N Y Acad Sci. 2002 Dec; 982: 46-69.
      Results of long-term experimental studies on the carcinogenicity of methyl
      alcohol and ethyl alcohol in rats.
      Soffritti M, Belpoggi F, Cevolani D, Guarino M, Padovani M, Maltoni C.
      Cancer Research Center, European Ramazzini Foundation for Oncology and
      Environmental Sciences, Bologna, Italy. crcfr@...
      MORANDO SOFFRITTI, FIORELLA BELPOGGI, DANIELA CEVOLANI, MARINA GUARINO,
      MICHELA PADOVANI, and CESARE MALTONI

      Methyl alcohol was administered in drinking water supplied ad libitum at
      doses of 20,000, 5,000, 500, or 0 ppm to groups of male and female
      Sprague-Dawley rats 8 weeks old at the start of the experiment.
      Animals were kept under observation until spontaneous death.
      Ethyl alcohol was administered by ingestion in drinking water at a
      concentration of 10% or 0% supplied ad libitum to groups of male and female
      Sprague-Dawley rats;
      breeders and offspring were included in the experiment.
      Treatment started at 39 weeks of age (breeders),
      days before mating,
      or from embryo life (offspring)
      and lasted until their spontaneous death.
      Under tested experimental conditions,
      methyl alcohol and ethyl alcohol were demonstrated to be carcinogenic for
      various organs and tissues.
      They must also be considered multipotential carcinogenic agents.
      In addition to causing other tumors,
      ethyl alcohol induced malignant tumors of the oral cavity, tongue, and lips.
      These sites have been shown to be target organs in man by epidemiologic
      studies. Publication Types: Review Review, Tutorial PMID: 12562628



      http://www.icoh.org.sg/reports/board_meeting_rome.html 2nd March 2002
      International Commission on Occupational Health

      ISPESL, National Institute for Occupational Safety and Prevention
      Via Fontana Candida 1 I-00040 Monteporzio Catone (Rome) Italy
      +39 06 94181407/204 Fax: +39 06 9418 1556 icohsg@...

      3. Presentation of the Collegium Ramazzini and its collaboration with ICOH
      ICOH has lately strengthen its collaboration with Collegium Ramazzini. Dr.
      Fiorella Belpoggi, Deputy Director of the Collegium Ramazzini, was invited
      to present the history and plans of the Collegium.

      The Collegium was founded 1982, 300 years after Ramazzini, to study
      occupational medicine around the world. The Collegium is managed by an
      Executive Committee. The membership comprises presently 182 people. The
      General Secretariat is located to Centeviglia, Italy where permanent
      localities are given to the Collegium. Dr. Belpoggi forwarded greetings from
      Professor Philip Landrigan, President of the Collegium and Dr. Soffritti,
      Vice President.
      Dr. Belpoggi expressed her gratitude to Bengt Knave for the invitation and
      for the meeting held in Stockholm in October 2001 with Prof. Landrigan and
      Dr. Soffritti. She confirmed that there are a number of areas of mutual
      interest. Invitation to the Collegium to participate actively in the ICOH
      Congress 2003 in Iguassu, Brazil had been gratefully accepted. The Collegium
      looks forward to interesting cooperation in future.

      Bengt Knave expressed ICOH's appreciation of the interest for more active
      collaboration between the Collegium and ICOH. For distribution of
      information about the planned meeting on Precautionary measures the ICOH
      membership list will be sent to the Collegium Ramazzini.



      "Examples of field studies that are focused on the effects of pesticides,
      air pollution and formaldehyde are used to illustrate advantages and
      limitations of biomarker studies in children."

      Mutat Res. 2005 Jul 4; [Epub ahead of print]

      Children's exposure to environmental pollutants and biomarkers of genetic
      damage I. Overview and critical issues.
      Neri M, Bonassi S, Knudsen LE, Sram RJ, Holland N, Ugolini D, Merlo DF.
      Unit of Epidemiology and Biostatistics, National Cancer Research Institute,
      Genoa, Italy; Institute of Public Health, University of Copenhagen,
      Copenhagen, Denmark.

      In the last decade, molecular epidemiological studies have provided new
      perspectives on studying environmental risks in pediatric populations, based
      on the growing understanding that children may be more susceptible to
      toxicants than adults.
      Protecting children's health is a social priority, and specific research
      programs have been initiated with this purpose in the United States and
      Europe.
      These programs address the development of
      (i) less invasive methods for biological specimens collection,
      (ii) specific tools for interpretation and validation of biomarkers,
      (iii) methods for translating biomarker results into intervention strategies
      and for integrating them with environmental monitoring and health data,
      (iv) optimal ways to obtain consent and provide information to children
      and/or their parents participating in the studies and
      (v) techniques for the effective communication with policy makers and the
      public. Critical issues in children's environmental research discussed in
      this paper include specific needs of study design, exposure assessment,
      sample collection and ethics.
      Special consideration is given to the autonomy of the child in giving
      consent,
      the details and nature of the information provided,
      and the need to warrant controlled access to sensitive information.
      The use of incentives such as gifts and payment to ensure the participation
      of school-aged children is specifically discussed.
      Examples of field studies that are focused on the effects of pesticides,
      air pollution and formaldehyde are used to illustrate advantages and
      limitations of biomarker studies in children. PMID: 16002329



      Mutat Res. 2005 Jul 1; [Epub ahead of print]
      Linking toxicology to epidemiology: Biomarkers and new technologies-Special
      issue overview.
      Garte S, Bonassi S.
      Genetics Research Institute, Milan, Italy; School of Public Health, UMDNJ,
      330 George St., New Brunswick, NJ 08903, USA.
      Publication Types: EDITORIAL PMID: 15996689



      Cytogenet Genome Res. 2004; 104(1-4): 376-82.
      Chromosomal aberrations and risk of cancer in humans: an epidemiologic
      perspective.
      Bonassi S, Znaor A, Norppa H, Hagmar L.
      Department of Environmental Epidemiology and Biostatistics, National Cancer
      Research Institute, Genoa, Italy. stefano.bonassi@...

      The pioneering papers published more than one century ago by Theodor Boveri
      opened the way to extensive research on the mechanism linking chromosomal
      abnormalities to the pathogenesis of cancer.
      As a result of this effort, robust theoretical and empirical evidence
      correlating cytogenetic damage to early stages of cancer in humans was
      consolidated, and an increased cancer risk was postulated in healthy
      subjects with high levels of chromosomal aberrations (CA).
      The first epidemiological investigation aimed at validating CA as predictor
      of cancer risk was carried out in the early 1990s.
      In that report the Nordic Study Group described an 80% increased risk of
      cancer in healthy subjects with high frequencies of CA.
      The results of this first study were replicated a few years later in a
      parallel research initiative carried out in Italy,
      and the subsequent pooled analysis of these two cohorts published in 1998
      contributed to refine the quantitative estimate of the CA/cancer
      association.
      A small case-control study nested in a cohort of subjects screened for CA in
      Taiwan found an increased risk in subjects with high frequency of
      chromosome-type CA,
      while in 2001 a significant increase of cancer incidence associated with
      high levels of CA was described in a new independent cohort of radon exposed
      workers from the Czech Republic.
      Despite some common limitations affecting study design,
      the studies cited above have provided results of great interest both for the
      understanding of mechanisms of early stages of carcinogenesis,
      and for their potential implication for cancer prevention.
      The recent evolution of molecular techniques and the refinement of high
      throughput techniques have the potential to improve the knowledge about the
      role of specific sub-types of CA
      and to provide further insight into the mechanisms.
      Finally, the most challenging perspective in the field is
      the passage from research to regulation,
      with the implementation of preventive policies based on the accumulated
      knowledge. Copyright 2003 S. Karger AG, Basel
      Publication Types: Review Review, Tutorial PMID: 15162068
      *************************************************************


      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: Murray 2004.08.08 2005.07.11

      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://www.epa.gov/iris/subst/0305.htm
      also http://www.china-pops.net/enwww/IRIS-Mirror/subst/0305.htm 1998.05.05

      USA Environmental Protection Agency EPA
      Integrated Risk Information System IRIS

      This site explains that the harmful rat dose of 500 mg/kg body weight per
      day was divided
      by 10 for "interspecies extrapolation" (the higher vulnerability of
      humans than rats),
      by 10 for "range of sensitivity" (the variation of individual human
      vulnerability), and
      by 10 for "subchronic to chronic exposure" (the increased danger from
      lifetime as compared to the 3 month exposure in the rat test),
      giving a total reduction of 10x10x10 = 1000 for the UF = Uncertainty Factor.

      The human Oral RfD is the rat Oral RfD divided by 1000, so
      500 mg/kg/day is reduced to 0.5 mg/kg/day , so that the allowed dose for a
      60 kg human is 30 mg oral methanol daily.

      Moreover, a recent study found that after 4 months of moderate oral
      aspartame, 12 rats took four times longer to finish a simple, one-turn
      maze-- an alarming level of neurotoxicity:

      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

      "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 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."

      The 11% methanol component of aspartame is immediately released in the GI
      tract, so these rats were being exposed to only 27.5 mg/kg/day methanol.

      The EPA IRIS on 1998.05.05 used a 1986 90 day rat study to find a
      No-Observed-Effect Level (NOEL) value of 500 mg/kg/day, which, divided by
      1000, became their human long-term safe methanol level of 0.5 mg per kg body
      weight per day, which for a 60 kg average person is 30 mg methanol daily,
      for oral exposure.

      However, the rat level is 18 times greater than that for the level of
      dramatic memory loss and clear-cut brain changes found by McConnaughey M,
      May 2004.

      This suggests reducing the human long-term safe level twenty times to
      .025 mg/kg/day = 25 micrograms per kg body weight per day,
      which for a 60 kg average person is 1.5 mg oral methanol per day.

      Since methanol from any source, once in the human blood stream, is always
      quickly and largely turned into formaldehyde and then formic acid, resulting
      in durable retained cumulative complex toxic products, this implies a
      somewhat smaller formaldehyde ingestion limit. A third of the methanol
      would lead to a limit of 0.5 mg ingested and inhaled formaldehyde daily for
      a 60 kg average person.


      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 1999 EPA level for
      formaldehyde in drinking water was 1 ppm, while recent WHO levels are 2.6
      ppm.

      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 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

      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 Usenet group: bionet.toxicology.


      http://groups.yahoo.com/group/aspartameNM/message/1184
      corporate corruption of health sciences, International Journal of
      Occupational and Environmental Health, entire issue, 2005 Oct-Dec: Gary N
      Greenburg, OEM-L: aspartame (methanol, formaldehyde, formic acid) toxicity,
      Murray 2005.07.14

      http://groups.yahoo.com/group/aspartameNM/message/1185
      Ramazzini Institute (Italy) lifetime study with 1800 rats shows aspartame at
      human use levels causes cancer (methanol, formaldehyde, formic acid), M
      Soffritti and F Belpoggi: Felicity Lawrence, The Guardian (UK): Murray
      2005.07.15

      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/782
      RTM: Smith, Terpening, Schmidt, Gums:
      full text: aspartame, MSG, fibromyalgia 2002.01.17 rmforall
      Jerry D Smith, Chris M Terpening, Siegfried OF Schmidt, and John G Gums
      Relief of Fibromyalgia Symptoms Following
      Discontinuation of Dietary Excitotoxins.
      The Annals of Pharmacotherapy 2001; 35(6): 702-706.
      Malcolm Randall Veterans Affairs Medical Center, Gainesville, FL, USA.
      BACKGROUND: Fibromyalgia is a common rheumatologic disorder that is
      often difficult to treat effectively.
      CASE SUMMARY: Four patients diagnosed with fibromyalgia syndrome
      for two to 17 years are described.
      All had undergone multiple treatment
      modalities with limited success. All had complete, or nearly complete,
      resolution of their symptoms within months after eliminating monosodium
      glutamate (MSG) or MSG plus aspartame from their diet.
      All patients were women with multiple comorbidities
      prior to elimination of MSG.
      All have had recurrence of symptoms whenever MSG is ingested.

      Siegfried O. Schmidt, MD Asst. Clinical Prof. siggy@...
      Community Health and Family Medicine, U. Florida, Gainesville, FL
      Shands Hospital West Oak Clinic Gainesville, FL 32608-3629
      352-376-5071
      **************************************************************
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