Loading ...
Sorry, an error occurred while loading the content.

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

Expand Messages
  • Rich Murray
    careful expert lifetime study on mice shows liver and lung cancers from aspartame, M Soffritti et al, Ramazzini Institute, Italy, checked by US National
    Message 1 of 1 , Mar 2, 2011
    View Source
    • 0 Attachment
      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
      http://rmforall.blogspot.com/2011_02_01_archive.htm
      Sunday, February 27, 2011
      [ at end of each long page, click on Older Posts ]
      http://groups.yahoo.com/group/aspartameNM/message/1619
      [you may have to Copy and Paste URLs into your browser]
      _______________________________________________


      "CONCLUSIONS

      The present study demonstrates for the first time that APM administered
      in feed to Swiss mice at doses of 32,000, 16,000, 8,000, 2,000, or 0
      ppm, starting the dietary exposure on day 12 of gestation and lasting
      until death, induces significant dose-related increases of
      hepatocellular carcinomas (P<0.01) and of alveolar/bronchiolar
      carcinomas (P<0.05) in males.
      In particular, the significant increased incidences of hepatocellular
      carcinomas were observed at the dietary levels of 32,000 ppm (P<0.01)
      and 16,000 ppm (P<0.05) and of lung alveolar/bronchiolar carcinomas at
      32,000 ppm (P<0.05).
      HCA and HCC (combined) resulted significantly increased (P<0.05) in the
      male group treated at 16,000 ppm.
      A/BA and A/BC (combined) resulted significantly increased (P<0.05) in
      the male group treated at 32,000 ppm.
      A significant dose-related trend (P<0.05) was also observed.

      Given that APM is completely metabolized in the gastrointestinal tract
      to phenylalanine, aspartic acid, and methanol, it may be concluded
      that the observed carcinogenic effects were caused not by APM itself
      but rather by its metabolites.

      In particular, it cannot be disregarded that the conversion of APM
      methanol into formaldehyde in the liver may result in a generation of
      formaldehyde adducts [Trocho et al., 1998], which could explain the
      plausibility of hepatocarcinogenic effects of APM in male mice.

      The fact that females did not develop a significantly increased
      incidence of liver tumors may be explained by the gender resistance,
      as already reported.

      On the basis of these results, together with previous carcinogenicity
      bioassays conducted on rats in our laboratories, APM should be
      considered a multiple site, transspecies carcinogenic agent.

      A re-evaluation of the current regulations on APM remains, in our
      opinion, urgent.

      ACKNOWLEDGMENTS

      This research was supported entirely by the Ramazzini Institute.
      The authors declare that they have no competing financial interests.
      The authors thank Dr. David Hoel for his great support in the
      statistical evaluation of the results.
      A special thanks to the U.S. National Toxicology Program for having
      organized a meeting of a group of pathologists at NIEHS in order to
      provide a second opinion regarding the pathological lesions observed
      in the APM Swiss mice study.
      Ten pathologists participated in the NTP histopathology review.
      The number of slides reviewed was 100 of which 26 were the subject of
      discussion.
      In the remaining cases, the original Ramazzini Institute diagnoses
      were confirmed.
      The lesions reviewed were liver adenomas/carcinomas and angiosarcomas;
      lung adenomas/carcinomas; lymphomas; skin fibrosarcomas; and a few
      miscellaneous lesions.

      With regard to the data presented in this manuscript (liver and lung
      tumors) there were no discrepancies between NTP and RI pathology
      evaluation."


      http://www.ncbi.nlm.nih.gov/pubmed/20886530

      Am J Ind Med. 2010 Sep 30. [Epub ahead of print]
      Aspartame administered in feed, beginning prenatally through life span,
      induces cancers of the liver and lung in male Swiss mice.
      Soffritti M, Belpoggi F, Manservigi M, Tibaldi E, Lauriola M, Falcioni L, Bua L.
      Cesare Maltoni Cancer Research Center, Ramazzini Institute,
      Bentivoglio, Bologna, Italy.
      Morando Soffritti MD,
      Fiorella Belpoggi DBS,
      Marco Manservigi DBS,
      Eva Tibaldi DBS,
      Michelina Lauriola PhD,
      Laura Falcioni DVM,
      Luciano Bua MD
      Article first published online: 30 SEP 2010
      DOI: 10.1002/ajim.20896
      Copyright © 2010 Wiley-Liss, Inc.

      Abstract

      BACKGROUND:
      Aspartame (APM) is a well-known intense artificial sweetener used in more
      than 6,000 products.
      Among the major users of aspartame are children and women of childbearing
      age.
      In previous lifespan experiments conducted on Sprague-Dawley rats we have
      shown that APM is a carcinogenic agent in multiple sites and that its
      effects are increased when exposure starts from prenatal life.
      OBJECTIVE:
      The aim of this study is to evaluate the potential of APM to induce
      carcinogenic effects in mice.
      METHODS:
      Six groups of 62-122 male and female Swiss mice were treated with APM in
      feed at doses of 32,000, 16,000, 8,000, 2,000, or 0 ppm from prenatal life
      (12 days of gestation) until death.
      At death each animal underwent complete necropsy and all tissues and organs
      of all animals in the experiment were microscopically examined.
      RESULTS:
      APM in our experimental conditions induces in males a significant
      dose-related increased incidence of hepatocellular carcinomas (P<0.01),
      and a significant increase at the dose levels of 32,000 ppm (P<0.01) and
      16,000 ppm (P<0.05).
      Moreover, the results show a significant dose-related increased incidence of
      alveolar/bronchiolar carcinomas in males (P<0.05),
      and a significant increase at 32,000 ppm (P<0.05).
      CONCLUSIONS:
      The results of the present study confirm that APM is a carcinogenic agent in
      multiple sites in rodents,
      and that this effect is induced in two species,
      rats (males and females) and mice (males).
      No carcinogenic effects were observed in female mice.
      Am. J. Ind. Med. � 2010 Wiley-Liss, Inc.
      PMID: 20886530

      American Journal of Industrial Medicine
      Copyright © 2010 Wiley-Liss, Inc., A Wiley Company
      Edited by: Steven B. Markowitz
      Impact Factor: 1.721
      ISI Journal Citation Reports © Ranking: 2009: 59/122 (Public Environmental &
      Occupational Health)
      Online ISSN: 1097-0274

      Recently Published Issues
      Current Issue: November 2010 Volume 53, Issue 11
      October 2010 Volume 53, Issue 10
      September 2010 Volume 53, Issue 9

      Abbreviations:
      APM, aspartame;
      CMCRC/RI, Cesare Maltoni Cancer Research Center/Ramazzini Institute;
      EFSA, European Food Safety Authority;
      EU, European Union;
      FDA, Food and Drug Administration.

      Cesare Maltoni Cancer Research Center, Ramazzini Institute,
      Bentivoglio, Bologna, Italy
      Contract grant sponsor: Ramazzini Institute.
      *Correspondence to: Morando Soffritti, Cesare Maltoni Cancer Research
      Center, Ramazzini Institute, Castello di Bentivoglio,Via Saliceto, 3,
      40010 Bentivoglio, Bologna, Italy. E-mail: soffrittim@...
      Accepted 30 July 2010
      DOI 10.1002/ajim.20896.
      Published online 30 September 2010 in Wiley Online Library
      (wileyonlinelibrary.com)

      ...APM is metabolized in the gastrointestinal tract by esterases and
      peptidases into three components: the amino acids phenylanine and
      aspartic acid, and methanol [Ranney et al., 1976].

      APM can be also absorbed into the mucosal cells prior to hydrolysis
      and then metabolized within the cell to its three components which
      then enter circulation [Mattews, 1984].

      Methanol is not subject to metabolism within the enterocyte and
      rapidly enters the portal circulation and is oxidized in the liver to
      formaldehyde, an highly reactive chemical which strongly binds to
      proteins [Haschemeyer and Haschemeyer, 1973] and nucleic acids
      [Metzler, 1977] forming formaldehyde adducts.

      In a study, in which APM, 14 C-labeled in the methanol carbon, was
      given orally to adult male Wistar rats for 10 days, it was shown that
      the carbon adducts of protein and DNA could have been generated only
      from formaldehyde derived from APM methanol.
      Moreover, it was suggested that the amount of formaldehyde adducts may
      be cumulative [Trocho et al., 1998].

      Several reviews conclude that APM is digested in all species in the
      same way [Ranney et al., 1976].
      Since APM is metabolized before entering the blood stream, there is no
      distribution of APM outside the gastrointestinal tract.

      Epidemiological studies conducted among users of artificial sweeteners
      (including APM) did not show an increased carcinogenic risk, except in
      one study which postulated an association of increased risk of brain
      cancer and use of APM [Olney et al., 1996].

      Studies performed by the US National ToxicologyProgram (NTP) in which
      groups of 15 males and 15 females of transgenic mice, p53
      haploinsufficient strain (p53) and Tg.AC homozygous strain (Tg.AC)
      dermal exposure model were treated with diets containing 0, 3, 125,
      6,250, 12,500, 25,000, or 50,000 ppm of APM for 40 weeks and then
      sacrificed did not show any carcinogenic responses [NTP, 2005].
      Overall there was no evidence of a positive response for tumors in
      animals treated with APM in feed up to 50,000 ppm.
      Although the studies did not show carcinogenic response, it should be
      noted that altered genetic mice were evaluated by NTP with the intent
      to develop faster, less costly and more predictive in vivo models for
      identifying potential chemical carcinogenic agents and that APM was
      selected as a presumed non-carcinogen.
      Pritchard et al. [2003] evaluated the NTP findings regarding the
      potential of transgenic mouse models to identify carcinogenic agents.
      The authors concluded that the Tg.AC dermal exposure model and p53
      oral exposure model had an overall accuracy of 74% in correctly
      predicting chemicals that are listed by the International Agency for
      Research on Cancer (IARC) and/or NTP in their respective lists of
      chemicals classified carcinogenic or probably carcinogenic in humans.
      The study concluded that the transgenic mouse models missed a number
      of known or probable human carcinogens, whereas long-term rodent
      bioassays missed none of these chemicals.

      Indeed, the authors of the studies performed by NTP concluded that the
      negative findings were of uncertain value:
      ‘‘because this is a new model, there is uncertainty whether the
      (aspartame) study possessed sufficient sensitivity to detect a
      carcinogenic effect’’ [NTP, 2005].
      In fact the P53 deficient transgenic model does not respond to
      non-genotoxic carcinogenic chemicals, and hence choosing that model
      confirmed this fact with APM.
      The NTP has since virtually discontinued the use of genetically
      modified models for identifying carcinogens.

      Long-term carcinogenicity bioassays performed on rats and mice in the
      early 1970s by industry did not show any carcinogenic effects.
      In female p53 haploinsufficient mice, the results of the micronucleus
      test were judged to be positive, based on a significant trend test and
      a small but statistically significant increased frequency of
      micronucleated erythrocytes in the 50,000 ppm group
      (P=0.028) [NTP, 2005].

      A detailed review and comments on the genotoxicity, long-term
      carcinogenicity studies in rodents and epidemiological studies
      available today on APM has been reported previously [Soffritti et al.,
      2005, 2006, 2007].
      Overall, we believe that the potential long-term toxic effects of APM,
      and in particular the carcinogenic effects, had not been adequately
      demonstrated by the long-term bioassays on rats and mice, mainly
      because of the small number of animals used per sex per group and the
      duration of the experiments (in which rodents were sacrificed at 110
      weeks of age, corresponding to the two-thirds of the lifespan).

      For these reasons we started a project encompassing several
      experiments on rats and mice in which APM was administered in feed at
      various doses to a large number of rats or mice per group per sex.
      Treatment started at different ages and lasted for different periods;
      rodents were always kept under observation until natural death to
      allow APM to express all its full carcinogenic potential.

      In the first experiment we demonstrated that APM, administered from 8
      weeks of age for the lifespan to Sprague–Dawley rats, induced a
      significantly increased incidence of lymphomas/leukemias and of
      neoplastic lesions of the renal pelvis and ureter in females, and a
      significantly increased incidence of malignant Schwannomas of the
      peripheral nerves in males [Soffritti et al., 2006].

      In a second experiment we showed that APM, administered from fetal
      life until natural death, caused lymphomas/leukemias in male and
      female rats and, for the first time, cancers of the mammary glands in
      females [Soffritti et al., 2007].
      Furthermore, this study demonstrated that when lifespan exposure
      starts during fetal life, the incidences of lymphomas/leukemias were
      increased in comparison to the treatment starting postnatally.
      Neither cranial Schwannomas nor neoplasms of the renal pelvis and
      ureter were observed in the second experiment.
      This result may be explained by the fact that the number of rats per
      sex per group in this study was lower and therefore the sensitivity of
      the study for this type of tumors may have been reduced....

      .... APM was pulverized in a standard pelleted diet at concentrations of
      0, 2,000, 8,000, 16,000, or 32,000
      to simulate an assumed daily APM intake of
      0, 250, 1,000, 2,000, and 4,000 mg/kg b.w.,
      and was administered to groups of 62–122 male and female Swiss mice
      from the 12th day of fetal life until death.
      The dose levels of APM were chosen on the basis of available data
      reported in the literature.
      The standard ‘‘Corticella diet’’ was provided by Laboratorio Dottori
      Piccioni, Milan, Italy;
      the same diet used for more than 30 years at the laboratory of the
      Cesare Maltoni Cancer Research Center (CMCRC).
      Fresh tap water was provided daily.
      The major constituents of the diet were: water 12%; raw protein 24%;
      raw fat 3.50%; raw fibers 5.50%; ashes 10.50%; non-nitrogenous extracts
      56.50%.
      The diet was analyzed for nutritional components, microorganisms, and
      possible contaminants (pesticides, metals, estrogen activity,
      nitrosamines, and aflatoxins) every 6 months, and disposed of if older
      than 3 months from the date of manufacture.
      The diet was formulated every 40–50 days.
      At room temperature APM is stable in food and liquid.
      The stability of APM in the feed was analyzed periodically during the
      experiment.
      Feed and water were supplied ad libitum.....

      ...DISCUSSION
      The present study, in which APM was administered in feed at the dose
      levels of 0, 2,000, 8,000, 16,000, or 32,000 ppm to Swiss mice from
      prenatal life until death, further confirms that APM induces
      carcinogenic effects in rodents.
      The study shows:
      (a) significant dose-related increase of hepatocellular carcinomas in
      males (P<0.01).
      Incidences were also significantly increased at the two top dietary
      concentrations of 32,000 ppm (P<0.01) and 16,000 ppm (P<0.05);
      (b) a significant dose-related increase of the incidence of lung
      alveolar/bronchiolar carcinomas (P<0.01), and at 32,000 ppm (P<0.05).
      Since the survival of the males was not affected by APM exposure, we
      used logistic analysis to evaluate the combined adenoma/carcinoma
      results of the liver and of the lung.
      The incidence of HCA and HCC combined resulted significantly increased
      (P<0.05) in the group treated at 16,000 ppm.
      No significant dose–response was observed.
      The reason for the lack of significance is that the dose–response is
      flat over the exposure groups while the controls are lower (i.e., 12.8,
      21.4, 21.0, 25.0, and 20.5).
      It is noticeable that until 98 weeks of age 8/55 deceased males
      (14.6%) treated at 32,000 ppm had HCC and no HCA.
      On the contrary, three HCA and no HCC were observed among the 60
      controls deceased in the same period.
      This may depend on a more rapid progression of preneoplastic lesions to HCC.
      However, others suggest that the response to carcinogens differ, and
      that both HCA and HCC may develop de novo, without going through the
      stage of foci of cellular alterations [Frith et al., 1979].
      A significant dose-related trend (P<0.05) of A/BA and A/BC combined
      was observed among males.
      Moreover, the incidence of A/BA plus A/BC in males treated at 32,000
      ppm was significantly increased (P<0.05) compared to controls.

      Both liver and lung carcinomas in all exposure groups of males were
      within the historical control range of these neoplasms in the CMCRC
      laboratory.

      Concerning the HCC, the concurrent control (5.1%) falls within the
      lower range of our historical controls (0–26.3%) and because the
      incidences of HCC in the groups treated at 32,000 (18.1%) and 16,000
      (15.6%) were over three and two times the concurrent control, we
      considered this effect related to the treatment.

      Concerning A/BC, the concurrent control (6.0%) falls also within the
      lower range of our
      historical controls (0–14.3%) and because the incidence observed at
      the highest dose was more than double the concurrent control we
      considered these effects to be related
      to APM exposure [Haseman et al., 1984; Haseman, 1992, 1995].

      No differences were observed in the incidences of liver and lung
      tumors among the females of treated and control groups.
      It has been reported that both spontaneously occurring and treatment
      induced hepatocellular tumors occur with significantly greater
      frequency and multiplicity in males
      than in females even though occasionally exceptions do occur [Maronpot, 2009].
      Male mice are also more susceptible to develop A/BA and A/BC than
      females [Hahn et al., 2007; Dixon et al., 2008].

      The carcinogenic effects observed in our mouse bioassay do not support
      the negative outcome obtained with the CD-1 mouse study performed at
      the Searle Laboratory in 1974 [Molinary, 1984].
      In that experiment one group of 72 male and female CD-1 mice (control)
      and three groups of 32 males and 32 females were treated,
      respectively, with APM in feed at the dose levels of 0, 1, 2, 4 g/kg
      from prenatal life for 2 years.
      These studies are not comparable for two reasons:
      (a) the number of the treated animals per sex per group is smaller in
      comparison to the number in our experiment and to the number requested
      by the current standard for carcinogenic bioassays (at least 50
      animals per sex per group) used by NTP
      and most others and
      (b) the length of observation is much shorter (110 weeks compared to
      130 weeks).
      Both of these factors result in a loss of sensitivity for detecting a
      carcinogenic effect.

      As already reported [Soffritti et al., 1999; Haseman et al., 2001;
      Huff et al., 2008; Soffritti et al., 2008], in longterm
      carcinogenicity bioassays the number of animals per sex/group and life
      span observation are critical points for identification and assessment
      of diffuse carcinogenic risks, defined as the exposure to a single or
      multiple agents or to mixtures that are expected to have limited
      carcinogenic potential because of the agent type (weak carcinogen)
      and/or dose/concentration (low), but that involve large group of the
      population (as is the case with APM).

      Concerning the prolonged (over 110 weeks of age) or lifespan duration
      of the experiment, we must consider that neoplastic response depends
      not only on the chemical–physical characteristics of the agent and its
      toxicological properties, the mode of exposure, and the type of
      animals, but also, to a greater extent, on the latency of the tumor
      which varies and may be very long.
      Truncating an experiment after 2 years (more or less two-thirds of the
      natural life of rodents) as requested by several regulatory agencies
      (and as practiced by NTP), may mask a possible carcinogenic response.
      This has been shown by us in experiments on benzene, Mancozeb (a
      widely used fungicide), vinyl acetate, toluene, and xylenes [Soffritti
      et al., 2002].
      It should be noted that in the experiment on toluene and xylenes
      performed by NTP, in which the rats were sacrificed after 104 weeks of
      treatment, no carcinogenic effects were found [Huff, 2002, 2003; Huff
      et al., 2010], whereas lifetime studies conducted in the CMCRC showed
      unequivocal carcinogenicity after 104 weeks [Maltoni et al., 1997;
      Soffritti et al., 2004].
      These two factors in our opinion makes the Searle study less sensitive
      than ours.

      Overall, the results of our integrated project of lifespan
      carcinogenic bioassays on APM conducted on Sprague–Dawley rats and
      Swiss mice are consistent in showing that under our experimental
      conditions APM must be considered a trans-species carcinogenic agent
      in multiple sites (Table V), inducing a significantly increased
      incidence of malignant tumors in:
      (a) multiple tissues in male and female rats;
      (b) multiple organs in male mice;
      (c) an earlier occurrence in treated animals and an higher incidence
      and an anticipated onset of cancers when the treatment starts from
      fetal life [Soffritti et al., 2007].

      Finally, the carcinogenic effects of APM in rats were shown also at
      dose levels of 100 and 20 mg/kg b.w. to which humans could be exposed
      [Soffritti et al., 2006, 2007].

      CONCLUSIONS

      The present study demonstrates for the first time that APM administered
      in feed to Swiss mice at doses of 32,000, 16,000, 8,000, 2,000, or 0
      ppm, starting the dietary exposure on day 12 of gestation and lasting
      until death, induces significant dose-related increases of
      hepatocellular carcinomas (P<0.01) and of alveolar/bronchiolar
      carcinomas (P<0.05) in males.
      In particular, the significant increased incidences of hepatocellular
      carcinomas were observed at the dietary levels of 32,000 ppm (P<0.01)
      and 16,000 ppm (P<0.05) and of lung alveolar/bronchiolar carcinomas at
      32,000 ppm (P<0.05).
      HCA and HCC (combined) resulted significantly increased (P<0.05) in the
      male group treated at 16,000 ppm.
      A/BA and A/BC (combined) resulted significantly increased (P<0.05) in
      the male group treated at 32,000 ppm.
      A significant dose-related trend (P<0.05) was also observed.

      Given that APM is completely metabolized in the gastrointestinal tract
      to phenylalanine, aspartic acid, and methanol, it may be concluded
      that the observed carcinogenic effects were caused not by APM itself
      but rather by its metabolites.

      In particular, it cannot be disregarded that the conversion of APM
      methanol into formaldehyde in the liver may result in a generation of
      formaldehyde adducts [Trocho et al., 1998], which could explain the
      plausibility of hepatocarcinogenic effects of APM in male mice.

      The fact that females did not develop a significantly increased
      incidence of liver tumors may be explained by the gender resistance,
      as already reported.

      On the basis of these results, together with previous carcinogenicity
      bioassays conducted on rats in our laboratories, APM should be
      considered a multiple site, transspecies carcinogenic agent.

      A re-evaluation of the current regulations on APM remains, in our
      opinion, urgent.

      ACKNOWLEDGMENTS

      This research was supported entirely by the Ramazzini Institute.
      The authors declare that they have no competing financial interests.
      The authors thank Dr. David Hoel for his great support in the
      statistical evaluation of the results.
      A special thanks to the U.S. National Toxicology Program for having
      organized a meeting of a group of pathologists at NIEHS in order to
      provide a second opinion regarding the pathological lesions observed
      in the APM Swiss mice study.
      Ten pathologists participated in the NTP histopathology review.
      The number of slides reviewed was 100 of which 26 were the subject of
      discussion.
      In the remaining cases, the original Ramazzini Institute diagnoses
      were confirmed.
      The lesions reviewed were liver adenomas/carcinomas and angiosarcomas;
      lung adenomas/carcinomas; lymphomas; skin fibrosarcomas; and a few
      miscellaneous lesions.

      With regard to the data presented in this manuscript (liver and lung
      tumors) there were no discrepancies between NTP and RI pathology
      evaluation.

      A special thanks to Luana De Angelis and to all the CRCCM staff who
      were involved in the study.

      REFERENCES

      Butchko HH, Stargel WW, Comer CP, Mayhew DA, Benninger C, Blackburn
      GL, de Sonneville LMJ, Geha RF, Hertelendy Z, Kostner A, Leon AS,
      Liepa GU, McMartin KE, Mendnhall CL, Munro IC, Novotny EJ, Renwick AG,
      Schiffman SS, Schomer DL, Shaywitz BA, Spiers PA, Tephly TR, Thomas
      JA, Trefz FK. 2002.
      Intake of aspartame vs the acceptable daily intake.
      Regul Toxicol Pharmacol 35:S13–S16.

      Decreto Legislativo 116. 1992.
      Attuazione della direttiva n. 86/609/CEE in materia di protezione
      degli animali utilizzati a fini sperimentali o ad altri fini scientifici
      [in Italian].
      Suppl Ordinario Gazz Ufficiale 40: 5–25.

      Dixon D, Herbert RA, Kissling GE, Brix AE, Miller RA, Maronpot RR. 2008.
      Summary of chemically induced pulmonary lesions in the National
      Toxicology Program (NTP) toxicology and carcinogenesis studies.
      Toxicol Pathol 36:428–439.

      European Food Safety Authority (EFSA). 2006.
      Opinion of the Scientific Panel on Food Additives, Flavourings,
      Processing Aids and Materials in contact with Food (AFC) on a request
      from the Commission related to a new long-term carcinogenicity study
      on aspartame.
      Question number EFSA-Q-2005-122.
      Adopted on 3 May 2006. EFSA J 356:1–44.

      Food and Drug Administration (FDA). 1981.
      Aspartame: Commissioner’s final decision.
      Fed Reg 46:38285–38308.

      Food and Drug Administration (FDA). 1983.
      Food additives permitted for direct addition to food for human
      consumption: Aspartame.
      Fed Reg 48:31376–31382.

      Food and Drug Administration (FDA). 1996.
      Food additives permitted for direct addition to food for human
      consumption: Aspartame.
      Fed Reg 61:33654–33656.

      Frith CH, Kodell RL, Littlefield NA. 1979.
      Biologic and morphologic characteristics of hepatocellular lesions in
      BALB/c female mice fed 2-acetylaminofluorene.
      In: Staffa JA, Mehlman MA, editors.
      Innovations in cancer risk assessment (ED01 study).
      Park Forest South, IL: Pathotox Publishers, Inc., p 121–138.

      Hahn FF, Gigliotti A, Hutt JA. 2007.
      Comparative oncology of lung tumors.
      Toxicol Pathol 35:130–135.

      Haschemeyer RH, Haschemeyer AEV. 1973.
      Proteins.
      New York: John Wiley & Sons, p 11–30.

      Haseman J. 1992.
      Value of historical controls in the interpretation of rodent neoplasm data.
      Drug Inf J 26:191–200.

      Haseman J. 1995.
      Data analysis: Statistical analysis and use of historical control data.
      Regul Toxicol Pharmacol 21:52–59.

      Haseman J, Huff JE, Boorman GA. 1984.
      Use of historical control data in carcinogenicity studies in rodents.
      Toxicol Pathol 12:126–135.

      Haseman J, Melnick R, Tomatis L, Huff J. 2001.
      Carcinogenesis bioassays: Study duration and biological relevance.
      Food Chem Toxicol 39(7):739–744.

      Hazardous Substances Data Bank. 2005.
      TOXNET: Toxicological Data Network.
      Available:
      http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~mobZuL:1
      [accessed August 3, 2005].

      Huff J. 2002.
      Chemicals studied and evaluated in long-term carcinogenesis bioassays
      by both the Ramazzini Foundation and the National Toxicology Program.
      In tribute to Cesare Maltoni and David Rall.
      Ann N Y Acad Sci 982:208–230.

      Huff J. 2003.
      Absence of carcinogenic activity in Fischer rats and B6C3F1 mice
      following 103-week inhalation exposures to toluene.
      Int J Occup Environ Health 9(2):138–146.

      Huff J, Jacobson MF, Davis DL. 2008.
      The limits of two-year bioassay exposure regimens for identifying
      chemical carcinogens.
      Environ Health Perspect 116(11):1439–1442.

      Huff J, Hejtmancik M, Eastin W. 2010.
      Carcinogenic activity of industrial grade mixed xylenes.
      Environ Health Perspect (in press).

      International Agency for Research on Cancer (IARC). 1973.
      Transplacental induction of tumors and malformations in rats treated
      with some chemical carcinogens.
      IARC Sci Publ 4:100–111.

      Maltoni C, Ciliberti A, Pinto C, Soffritti M, Belpoggi F, Menarini L. 1997.
      Results of long-term experimental carcinogenicity studies of the
      effects of gasoline, correlated fuels and major gasoline aromatics on
      rats.
      Ann N Y Acad Sci 837:15–52.

      Maronpot RR. 2009.
      Biological basis of differential susceptibility to
      hepatocarcinogenesis among mouse strains.
      J Toxicol Pathol 22: 11–33.

      Mattews DM. 1984.
      Absorption of peptides, amino acids, and their methylated derivatives.
      In: Stegink LD, Filer LJ, Jr., editors.
      Aspartame physiology and biochemistry.
      New York: Dekker, p 29–46.

      Mazur RH. 1984.
      Discovery of aspartame.
      In: Stegink LD, Filer LJ, Jr., editors.
      Aspartame physiology and biochemistry.
      New York: Dekker, p 3–9.

      Metzler DE. 1977.
      Biochemistry.
      New York: Academic Press, p 90–107.

      Molinary SV. 1984.
      Preclinical studies of aspartame in nonprimate animals.
      In: Stegink LD, Filer LJ, Jr., editors.
      Aspartame physiology and biochemistry.
      New York: Dekker, p 289–306.

      National Toxicology Program (NTP). 2005.
      Genetically Modified Model Report.
      Toxicology Studies of Aspartame (CAS NO. 22839-47-0)
      in Genetically Modified (FVB Tg.AC Hemizygous) and B6.129-Cdkn2atm1Rdp
      (N2) Deficient Mice and Carcinogenicity Studies of
      Aspartame in Genetically Modified [B6.129-Trp53tm1Brd (N5)
      Haploinsufficient] Mice (Feed Studies).
      NTP GMM1. National Toxicology Program,
      Research Triangle Park. Available at:
      http://ntp.niehs.nih.gov/%ef%ac%81les/GMM1-Web.pdf.

      Olney JW, Farber NB, Spitznagel E, Robins LN. 1996.
      Increasing brain tumor rates: Is there a link to aspartame?
      J Neuropathol Exp Neurol 55:1115–1123.

      Pritchard JB, French JE, Davis BJ, Haserman JK. 2003.
      The role of transgenic mouse models in carcinogen identification.
      Environ Health Perspect 111:444–454.

      Ranney RE, Opperman JA, Maldoon E, McMahon FG. 1976.
      Comparative metabolism of aspartame in experimental animals and
      humans.
      J Toxicol Environ Health 2:441–451.

      Soffritti M, Belpoggi F, Minardi F, Bua L, Maltoni C. 1999.
      Megaexperiments to identify and assess diffuse carcinogenic risks.
      Ann N Y Acad Sci 895:34–55.

      Soffritti M, Belpoggi F, Minardi F, Maltoni C. 2002.
      Ramazzini Foundation cancer program: History and major projects,
      life-span carcinogenicity bioassay design, chemicals studied, and
      results.
      Ann N Y Acad Sci 982:26–45.

      Soffritti M, Belpoggi F, Padovani M, Lauriola M, Degli Esposti D,
      Minardi F. 2004.
      Life-time carcinogenicity bioassays of toluene given bay stomach tube
      to Sprague–Dawley rats.
      Eur J Oncol 9:91–102.

      Soffritti M, Belpoggi F, Degli Esposti D, Lambertini L. 2005.
      Aspartame induces lymphomas and leukaemias in rats.
      Eur J Oncol 10:107–116.

      Soffritti M, Belpoggi F, Degli Esposti D, Lambertini L, Tibaldi E,
      Rigano A. 2006.
      First experimental demonstration of the multipotentialcarcinogenic
      effects of aspartame administered in the feed to Sprague–Dawley rats.
      Environ Health Perspect 114:379–385.

      Soffritti M, Belpoggi F, Tibaldi E, Esposti DD, Lauriola M. 2007.
      Lifespan exposure to low doses of aspartame beginning during prenatal
      life increases cancer effects in rats.
      Environ Health Perspect 115:1293–1297.

      Soffritti M, Belpoggi F, Esposti DD, Falcioni L, Bua L. 2008.
      Consequences of exposure to carcinogens beginning during developmental life.
      Basic Clin Pharmacol Toxicol 102(2):118–124.

      Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X, Fernandez-Lopez
      JA, Alemany M. 1998.
      Formaldehyde derived from dietary aspartame binds to tissue components in vivo.
      Life Sci 63:337–349.
      _______________________________________________


      M Soffritti of Ramazzini Foundation answers critique by Ajinomoto funded BA
      Magnuson and GM Williams re aspartame (methanol) carcinogenicity,
      Environmental Health Perspectives 2008 May: Murray 2008.06.24
      http://rmforall.blogspot.com/2008_06_01_archive.htm
      Tuesday, June 24, 2008
      http://groups.yahoo.com/group/aspartameNM/message/1543
      [ Extract ]

      ... http://groups.yahoo.com/group/aspartameNM/message/1441
      Lifetime exposure to low doses of aspartame beginning during prenatal life
      increases cancer effects in rats, Morando Soffritti et al, European
      Ramazzini Foundation, USA EPA Environmental Health Perspectives 2007.06.13
      free full text 24 pages: Murray 2007.06.16
      www.ehponline.org/members/2007/10271/10271.pdf free full text 24 pages

      Soffritti M, Belpoggi F, Lambertini L, Lauriola M.
      Results of long-term experimental studies on the carcinogenicity of
      formaldehyde and acetaldehyde in rats. In: Mehlman MA, Bingham E,
      Landrigan PJ, et al.
      Carcinogenesis bioassays and protecting public health.
      Commemorating the lifework of Cesare Maltoni and colleagues.
      Ann NY Acad Sci 2002; 982: 87-105.

      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

      Soffritti M, Belpoggi F, Cevolani D, Guarino M, Padovani M, Maltoni C.
      Results of long-term experimental studies on the carcinogenicity of methyl
      alcohol and ethyl alcohol in rats. In: Mehlman MA, Bingham E, Landrigan PJ,
      et al.
      Carcinogenesis bioassays and protecting public health.
      Commemorating the lifework of Cesare Maltoni and colleagues.
      Ann NY Acad Sci 2002; 982: 46-69.

      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.....


      http://www.ramazzini.it/ricerca/blogDetail.asp?id=31

      April 02, 2009
      Hazard Assessment deadline for science re aspartame (methanol,
      formaldehyde, formic acid) toxicity California Office of Environmental
      Health Hazard Assessment deadline May 5 for science re aspartame
      (methanol, formaldehyde, formic acid) toxicity -- folic acid protects:
      Stephen Fox: Rich Murray 2009.03.24
      http://rmforall.blogspot.com/2009_03_01_archive.htm
      Tuesday, March 24, 2009
      http://groups.yahoo.com/group/aspartameNM/message/1571

      http://www.opednews.com/populum/diarypage.php?did=12485#

      March 11, 2009 at 23:10:52

      California Opens Proposition 65 File, Could Lead to aspartame State
      Suits re: Carcinogenic Properties

      Diary Entry by Stephen Fox.....

      http://www.ramazzini.it/ricerca/newsDetail.asp?id=25

      news archive|archivio notizie
      overview/sommario
      November 15, 2008
      EHP: limits of bioassay exposure regimens
      EHP commentary argues the limits of 2-year bioassay exposure regimens:
      Ramazzini lifespan studies aspartame and toluene cited.

      In a recent commentary entitled "The limits of 2-Year Bioassay
      Exposure Regimens for Identifying Chemical Carcinogens"Environ Health
      Perspect 116:11, 2008, authors James Huff, Devra Davis and Michael
      Jacobson argue that the sensitivity of chemical carcinogenesis
      bioassays would be enhanced by exposing rodents beginning in utero and
      continuing for 30 months (130 weeks) or until their natural deaths at
      up to about 3 years.
      Citing lifespan studies conducted by the European Ramazzini Foundation on
      aspartame and toluene the authors conclude that observing rodents
      until their natural deaths (i.e the Ramazzini lifespan model)
      increases the sensitivity of bioassays, avoids false-negative results,
      and strengthens the value and validity of results for regulatory
      agencies.


      http://www.ramazzini.it/istituto/staff.asp

      http://www.ramazzini.it/centro_di_saggio/aboutus.asp

      About us

      The EEL of the Ramazzini Institute is a Contract Research Organisation
      specialized in non-clinical toxicological studies required for international
      Drug Registration and Notification of Chemical Substances, founded in 2009,
      sited in Bentivoglio (Bologna), Italy.

      Since 2009, the EEL has been subject to regular GLP inspection by Italian
      authorities and on February 2010 received the certificate of working in
      compliance with the GLP standards.

      Research Expertise:

      Repeated Dose Toxicity Studies
      Chronic Toxicity and Carcinogenicity Studies
      Toxicokinetics Studies (only the in vivo phase)
      Expertise Services:
      Biophase (in vivo phase)
      Pathology: Gross Necropsy, Histopathology and Peer Review
      Consultancy Services
      Bibliographic Services
      Archive: Data Storage
      The research team of EEL supplies the highest level of scientific knowledge,
      quality standards and regulatory competence to their customer's requests,
      whether for routine studies or specific complex and innovative projects.

      Staff members are:

      Director of the EEL
      Fiorella Belpoggi, DBS

      Quality Assurance
      Lucia Bortoluzzi, DBS
      Daniela Chiozzotto, PHD

      Head of Archives
      Luana de Angelis, High School Diploma, Chemistry

      Head of Unit
      Luciano Bua, MD
      Laura Falcioni, DVM
      Michelina Lauriola, PHD
      Eva Tibaldi, DBS

      Researchers
      Damiano Accurso, DVM
      Marco Manservigi, DBS
      Fabiana Manservisi, DBS

      Animal care and health
      Giovanni Vecchi, DVM

      http://www.ramazzini.it/istituto/contatti.asp

      tel 051.302252 fax 051.302245 info@...;

      DIREZIONE SCIENTIFICA
      tel 051.6640460 int. 1 crcdir@...;

      CENTRO DI RICERCA SUL CANCRO "CESARE MALTONI"
      Castello di Bentivoglio, via Saliceto, 3 - 40010 Bentivoglio (BO)
      tel 051.6640460 fax 051.6640223

      Direzione belpoggif@...;

      Servizi e laboratorio BPL servizi@...;

      Ufficio Stampa ed Eventi events@...;

      Invio curriculum lauriolam@...;

      Centro di Ricerche Epidemiologiche crcre@...;

      POLIAMBULATORIO ONCOLOGICO
      Via Libia, 13/a 40138 Bologna
      tel. 051-302252 fax 051-302245 info@...;


      http://www.collegiumramazzini.org/executivecouncil.asp

      Executive Council

      President: Philip J. Landrigan, MD, MSc, DIH
      Professor and Chairman, Department of Community and Preventive Medicine,
      The Mount Sinai School of Medicine,
      New York, NY, USA.

      Secretary General: Morando Soffritti, MD
      Scientific Director,
      Ramazzini Institute,
      Bologna, Italy.

      Treasurer: Nachman Brautbar, MD
      University of California School of Medicine,
      Los Angeles, CA, USA.

      Councilors: Henry Anderson, MD
      Wisconsin Department of Health and Social Services,
      Madison, WI, USA.

      Fiorella Belpoggi
      Director, Cesare Maltoni Cancer Research Center,
      Ramazzini Institute, Bologna, Italy.

      Massimo Crespi, MD
      Director Emeritus, Istituto Regina Elena,
      Rome, Italy.

      Philippe Grandjean, PhD
      Department of Environmental Medicine, Institute of Public Health, University
      of Southern Denmark,
      Odense, Denmark.

      James M. Melius, MD, Dr.P.H.
      Director, New York State Laborers' Health and Safety Trust Fund,
      Albany, NY, USA.

      Karel Van Damme, PhD
      Center for Human Genetics, University of Leuven,
      Leuven- Heverlee, Belgium.

      http://www.collegiumramazzini.org/fellows.asp

      over 200 experts listed

      Fellows:

      Ahlbom Anders
      Albin Maria
      Anderson Henry A.
      Andrews John S. Jr.
      Anwar Wagida A.
      Aragon Aurora
      Araki Shunichi
      Ashford Nicolas A.
      Au William W.
      Basaran Ayse Nursen
      Belpoggi Fiorella
      Berlin Maths
      Bertollini Roberto
      Bingham Eula
      Birnbaum Linda
      Blair Aaron Earl
      Boden Leslie
      Brautbar Nachman
      Bucher John
      Bulat Petar
      Casteleyn Ludwine
      Castleman Barry
      Cheong Hae Kwan
      Cherniack Martin G.
      Christiani David C.
      Claudio Luz
      Cogliano Vincent James
      Comba Pietro
      Cordier Sylvaine
      Corra Lilian A.
      Cranor Carl F.
      Crespi Massimo
      Davis Devra Lee
      De Rosa Christopher T.
      Dement John M.
      Dobbin R. Denny
      Donnelly Thomas P.
      Duffy Richard M.
      Ehrlich Rodney
      Ellingsen Dag G.
      Englund Anders
      Falk Henry
      Finkelman Jacobo
      Foà Vito
      Forastiere Francesco
      Franco Giuliano
      Frank Arthur
      Froines John
      Froneberg Brigitte
      Frumkin Howard
      Fucic Aleksandra
      Gee David
      Giannasi Fernanda
      Gochfeld Michael
      Goldman Lynn
      Goldstein Bernard D.
      Grandjean Philippe
      Graziano Joseph H.
      Greenberg Morris
      Groth David H.
      Guo Yue-Liang Leon
      Gut Ivan
      Ha Eun-Hee
      Harari Raul
      Hardell Lennart
      Hay Alastair
      Heinzow Birger G.J.
      Hermanus Mavis A.
      Hoel David G.
      Howard Charles Vyvyan
      Hryhorczuk Daniel
      Huff James
      Husgafvel-Pursiainen Kirsti
      Infante Peter F.
      Jackson Richard J.
      Jakubowski Marek
      Jarvholm Bengt
      Jensen Tina Kold
      Joshi Tushar Kant
      Katsouyanni Klea
      Kelsey Karl T.
      Kilburn Kaye H.
      Kogevinas Manolis
      Kogi Kazutaka
      Koh David S.Q.
      Landrigan Philip
      Langard Sverre
      Lanphear Bruce P.
      Lemen Richard A.
      Lerman Yehuda
      Levin Stephen M.
      Li Guilan
      Lioy Paul J.
      London Leslie
      Lucchini Roberto G.
      Lynge Elsebeth
      Markowitz Steven B.
      McDiarmid Melissa A.
      Mehlman Myron A.
      Melius James M.
      Melnick Ronald L.
      Minardi Franco
      Mirer Franklin E.
      Misra Usha Kant
      Moccaldi Antonio
      Myers Jonathan E.
      Natali Pier Giorgio
      Needleman Herbert L.
      Newman Lee S.
      Ngowi Aiwerasia Vera Festo
      Niemeier Richard W.
      Nordberg Gunnar
      Nuwayhid Iman A.
      Okubo Toshiteru
      Olden Kenneth
      Oliver L. Christine
      Omenn Gilbert S.
      Ozonoff David M.
      Paek Domyung
      Pelclova Daniela
      Pershagen Goran
      Poje Gerald V.
      Rantanen Jorma
      Rest Kathleen M.
      Ribak Joseph
      Rice Carol H.
      Richter Elihu D.
      Ringen Knut
      Rinsky Robert A.
      Ritz Beate
      Rogan Walter J.
      Rosenman Kenneth D.
      Rosenstock Linda
      Ruchirawat Mathuros
      Rydzynski Konrad J.
      Santos-Burgoa Carlos
      Sardas Semra
      Sasco Annie Jeanne
      Sass Jennifer
      Silbergeld Ellen K.
      Sly Peter D.
      Soffritti Morando
      Songnian Yin
      Sorsa Marja
      Soskolne Colin L.
      Straif Kurt
      Suk William A.
      Takahashi Ken
      Takala Jukka
      Tarkowski Stanislaw
      Taskinen Helena
      Teitelbaum Daniel T.
      Thorborg Marina
      Tompa Anna
      Toren Kjell O.
      Vainio Harri
      Van Damme Karel
      Vineis Paolo
      Wagner Gregory R.
      Wang Jung-Der
      Wardenbach Peter
      Watterson Andrew
      Wedeen Richard P.
      Wegman David H.
      Wesseling Catharina
      White Roberta F.
      Wolff Mary S.
      Xia Zhao-Lin
      Xintaras Charles
      Yano Eiji

      Emeritus Fellows:

      Bailar III John C.
      Barrett J. Carl
      Beliczky Louis S.
      Chiriboga Jorge
      Dooge James C.I.
      Fischbein S. Alf
      Fraumeni Joseph F. Jr.
      Harington John S.
      Hogstedt Christer
      Holmberg Bo E.G.
      Izmerov Nikolai F.
      Johnson Barry L.
      Kelman Howard R.
      LaDou Joseph
      Levy Barry S.
      Lucier George W.
      McCloskey Michael J.
      McGlashan Neil D.
      Merchant James A.
      Milham, Samuel
      Miller Albert
      Muir David C.F.
      Nefedov Oleg M.
      Noweir Madbuli H.
      Paladini Giuseppe
      Pott Friedrich
      Rappe Christoffer
      Samuels Sheldon
      Sugimura Takashi
      Suzuki Yasunosuke
      Upton Arthur C.
      Westerholm Peter J.M.
      Woitowitz Hans-Joachim
      Zampi Giancarlo


      Contact

      The International Headquarters of the Collegium Ramazzini have been provided
      by the town of Carpi in honor of its famous son, and are located in the
      Castle of Pio, home of the Princes of Carpi.

      The General Secretariat of the Collegium is located in the Castle of
      Bentivoglio near Bologna, Italy.
      Since the early 1970s the Castle has also been home to the Cesare Maltoni
      Cancer Research Center of the European Foundation of Oncology and
      Environmental Sciences "B. Ramazzini", established by Collegium Ramazzini
      co-founder, Professor Cesare Maltoni.

      General Secretariat
      Castello di Bentivoglio
      Via Saliceto, 3
      40010 Bentivoglio, Bologna, Italy

      General Secretary
      Dr. Morando Soffritti, M.D

      Executive Secretary
      Kathryn Knowles
      skype: kathrynknowles collegium@...;

      Ramazzini Days
      Federica Scagliarini
      Tel. +39 051.6640460 Fax. +39 051.6640223 events@...;


      http://www.unboundmedicine.com/medline/ebm/research/aspartame

      Zygler A, Wasik A, Namiesnik J
      Retention behaviour of some high-intensity sweeteners on different SPE
      sorbents. [Journal Article]
      Talanta 2010 Oct 15; 82(5):1742-8.

      Alleva R, Borghi B, Santarelli L, et al.
      In vitro effect of aspartame in angiogenesis induction. [JOURNAL ARTICLE]
      Toxicol In Vitro 2010 Sep 10.

      Cabaniols C, Giorgi R, Chinot O, et al.
      Links between private habits, psychological stress and brain cancer: a
      case-control pilot study in France. [JOURNAL ARTICLE]
      J Neurooncol 2010 Sep 11.

      Fernández-Maestre R, Hill HH
      Ion mobility spectrometry for the rapid analysis of over-the-counter
      drugs and beverages. [JOURNAL ARTICLE]
      Int J Ion Mobil Spectrom 2009 Aug; 12(3):91-102.

      Schoeb TR, McConnell EE
      Commentary: Further Comments on Mycoplasma pulmonis and Lymphoma in
      Bioassays of Rats. [JOURNAL ARTICLE]
      Vet Pathol 2010 Aug 17.

      Alsuhaibani ES
      In vivo cytogenetic studies on aspartame. [Journal Article] Comp Funct
      Genomics 2010.

      Yang Q
      Gain weight by "going diet?" Artificial sweeteners and the
      neurobiology of sugar cravings: Neuroscience 2010. [Journal Article]
      Yale J Biol Med 2010 Jun; 83(2):101-8.

      Nseir W, Nassar F, Assy N
      Soft drinks consumption and nonalcoholic fatty liver disease. [Editorial]
      World J Gastroenterol 2010 Jun 7; 16(21):2579-88.

      Anton SD, Martin CK, Han H, et al.
      Effects of stevia, aspartame, and sucrose on food intake, satiety, and
      postprandial glucose and insulin levels. [Journal Article, Research
      Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
      Appetite 2010 Aug; 55(1):37-43.
      _______________________________________________


      re GC Ebers study, females harmed more by body making methanol into
      formaldehyde in brain via ADH enzyme: 589 references, WC Monte,
      retired Prof. Nutrition: Rich Murray 2011.01.08
      http://rmforall.blogspot.com/2011_01_01_archive.htm
      Saturday, January 8, 2011
      [ at end of each long page, click on Older Posts ]
      http://groups.yahoo.com/group/aspartameNM/message/1614
      [you may have to Copy and Paste URLs into your browser]


      Woodrow C Monte, PhD, Emiritus Prof. Nutrition gives many PDFs of
      reseach -- methanol (11% of aspartame) puts formaldehyde into brain
      and body -- multiple sclerosis, Alzheimer's, cancers, birth defects,
      headaches: Rich Murray 2010.05.13
      http://rmforall.blogspot.com/2010_05_01_archive.htm
      Thursday, May 13, 2010
      http://groups.yahoo.com/group/aspartameNM/message/1601

      [ Other formaldehyde sources include alcohol drinks and
      tobacco and wood smoke,
      while adequate folic acid levels protect most people. ]

      http://whilesciencesleeps.com/about

      http://while-science-sleeps.com/references/pdf/586
      [ summary, not peer reviewed ]
      Monte WC.
      Methanol: A chemical Trojan horse as the root of the inscrutable U.
      Medical Hypotheses 2010;74(3):493-6
      DOI 2010.10.16

      Monte WC.
      Bittersweet: Aspartame Breast Cancer Link.
      Fitness Life 2008 Jan. 34: 32-36

      Monte WC.
      A Deadly Experiment. Methanol and MS,
      Fitness Life 2007 Dec. 34: 36-41

      Monte WC.
      Sickly Sweet: Is your Diet Sweetener killing you?
      Fitness Life 2007 Nov. 33: 31-33

      http://whilesciencesleeps.com/references
      589 references for above articles and upcoming book

      http://whilesciencesleeps.com/montediet
      [ and Fitness Life 2007 Dec. 34: 36-41 ]

      Methanol: Where Is It Found? How Can It Be Avoided?

      AVOID the following, ranked in order of greatest danger:

      1. Cigarettes.
      2. Diet foods and drinks with aspartame.
      3. Fruit and vegetable products and their juices in bottles,
      cans, or pouches.
      4. Jellies, jams, and marmalades not made fresh and kept
      refrigerated.
      5. Black currant and tomato juice products, fresh or
      processed.
      6. Tomato sauces, unless first simmered at least 3 hours
      with an open lid.
      7. Smoked food of any kind, particularly fish and meat.
      8. Sugar-free chewing gum.
      9. Slivovitz: You can consume one alcoholic drink a day
      on this diet -- no more! [ no fruit brandies ]
      10. Overly ripe or near rotting fruits or vegetables.

      Selection from Article 2, Fitness Life, December 2007, and
      well discussed in the DVD video:

      "Identical Symptoms of MS, Methanol Poisoning
      and Aspartame Toxicity

      The symptoms of multiple sclerosis (44, 83, 85, 169), chronic
      and acute methanol poisoning (13, 144, 189), and Aspartame
      toxicity (54, 58, 93, 181), are in all ways identical.

      There is nothing that happens to the human body from the
      toxic effect of methanol that has not been expressed during
      the course of MS... nothing (143, 144).

      This generalization extends even to the remarkable
      opthomological conditions common to both: transitory optic
      neuritis and retrolaminar demyelinating optic neuropathy with
      scotoma of the central visual field (which occasionally
      manifests as unilateral temporary blindness (85, 138, 163).

      In fact, these opthomological symptoms have been thought of
      for years in their respective literatures to be "tell tale"
      indications for the differential diagnosis for each of these
      maladies independently (85, 138, 148, 163, 169).

      The common symptoms of
      headache (13, 83, 181, 189),
      nervousness (13, 83, 181),
      depression (58, 83, 189, 181),
      memory loss (18, 147, 85, 169, 181),
      tingling sensations (13, 85, 168, 138, 169),
      pain in the extremities (13, 85, 169),
      optic neuritis (85, 138, 148, 163, 169),
      bright lights in the visual field (139, 83),
      seizures (21, 83, 160),
      inability to urinate or to keep from urinating (139, 146, 167)
      are all shared by each of these conditions and shared yet
      again by complaints from aspartame poisoning
      (54, 58, 93, 181).

      I take these strikingly similar symptom patterns as evidence
      that these disorders act on identical components of the
      central nervous system and in the same way.

      The "Miracle" that MS shares with Methanol poisoning

      In the early stages of MS, or when a non-lethal dose of
      methanol has been administered, complete recovery is a
      possibility.

      The only two afflictions for which such dramatic "remissions"
      are reported from identical neuromuscular and opthomological
      damage, even "blindness" is relapsing-remitting multiple
      sclerosis (85) and methyl alcohol poisoning (138, 163).

      The pathology of the two maladies is in may ways identical,
      particularly when it comes to destruction of the myelin
      sheath with no harm to the axon itself (18, 148, 176).

      Sex Ratios for MS and Aspartame Reactions

      Women bear the brunt of multiple sclerosis (91a-c) and lupus
      (SLE)(73) with fully three-fold representations in infliction
      numbers over men for both diseases.

      This is exactly the proportion represented by adverse
      reactors to Aspartame reported by the US Center for
      Disease Control in their study of 1984 (58).

      The Center found three women to every man whose
      Aspartame consumption complaints were serious enough
      to warrant investigation (93).

      Although the female/male ratio for those stricken with MS has
      always been high, recent estimates place it at over 3 to 1
      (91, 91a, 91c).

      What might account for the difference across sexes in
      incidence?

      A study published in the New England Journal of Medicine
      (94) reports biopsies of the gastric lining of men and women.

      A result was that the concentration of ADH in the
      gastric lining of men was much higher than for woman.

      Men have the advantage of removing methanol from the
      bloodstream four times faster on an equal-body-size basis
      than women.

      Thus, for men, methanol is more likely to be removed from the
      blood before it reaches the brain.

      The brain is spared but the methanol removed would still be
      metabolized to formaldehyde in the gut where it would reap
      its havoc on a more forgiving organ.

      This may help explain why men have more gastrointestinal
      complaints from both methanol and Aspartame consumption
      (93, 99).

      On the other hand, women's complaints from both more
      frequently involve serious neurological complications."...
      ______________________________________________


      Chemico-Biological Interactions, JA Bond, MA Medinsky, can share WC
      Monte paradigm re harm by formaldehyde via ADH enzyme & methanol in
      blood capillaries -- tobacco, wood smoke; dark wines, liquors;
      aspartame; canned tomatoes: Rich Murray 2011.02.21
      http://rmforall.blogspot.com/2011_02_01_archive.htm
      Monday, February 21, 2011
      [ at end of each long page, click on Older Posts ]
      http://groups.yahoo.com/group/aspartameNM/message/1618
      [you may have to Copy and Paste URLs into your browser]

      methanol (11% of aspartame), made by body into
      formaldehyde in many vulnerable tissues, causes modern
      diseases of civilization, summary of a century of research,
      Woodrow C Monte PhD, Medical Hypotheses journal:
      Rich Murray 2009.11.15
      http://rmforall.blogspot.com/2009_11_01_archive.htm
      Sunday, November 15, 2009
      [ at end of each long page, click on Older Posts ]
      http://groups.yahoo.com/group/aspartameNM/message/1589
      [you may have to Copy and Paste URLs into your browser]

      aspartame abstinance cures fibromyalgia chronic pain in 2 French
      adults: R Ciappuccini et al, Clin Exp Rheumatol 2010 Nov: Rich Murray
      2010.02.19
      http://rmforall.blogspot.com/2011_02_01_archive.htm
      Saturday, February 19, 2011
      [ at end of each long page, click on Older Posts ]
      http://groups.yahoo.com/group/aspartameNM/message/1617
      [you may have to Copy and Paste URLs into your browser]

      formaldehyde from 0.2 mg daily methanol from aspartame in Singulair
      (montelukast) chewable asthma medicine causes severe allergic
      dermatitis in boy, SE Jacob et al, Pediatric Dermatology 2009 Nov:
      Rich Murray 2010.09.27
      http://rmforall.blogspot.com/2010_09_01_archive.htm
      Monday, September 27, 2010
      [ at end of each long page, click on Older Posts ]
      http://groups.yahoo.com/group/aspartameNM/message/1613
      [you may have to Copy and Paste URLs into your browser]
      ______________________________________________


      Rich Murray, MA
      Boston University Graduate School 1967 psychology,
      BS MIT 1964, history and physics,
      1943 Otowi Road, Santa Fe, New Mexico 87505
      505-819-7388 rmforall@...

      http://groups.yahoo.com/group/AstroDeep/messages

      http://RMForAll.blogspot.com new primary archive

      http://groups.yahoo.com/group/aspartameNM/messages
      group with 118 members, 1,619 posts in a public archive

      http://groups.yahoo.com/group/aspartame/messages
      group with 1226 members, 24,283 posts in a public archive

      http://groups.yahoo.com/group/rmforall/messages

      participant, Santa Fe Complex www.sfcomplex.org
      ______________________________________________
    Your message has been successfully submitted and would be delivered to recipients shortly.