Obfuscation of the iatrogenic autism epidemic re mercury in kid
vaccines, Kenneth P. Stoller, Pediatrics 2006.05.06; aspartame toxicity
2005.11.10: Comet assay can test genotoxicity,
EFSA admits ignorance re methanol residues, Murray 2006.05.10
http://groups.yahoo.com/group/aspartameNM/message/1339

"Of course, everyone chooses, as a natural priority,
to actively find, quickly share, and positively act upon the facts
about healthy and safe food, drink, and environment."

Rich Murray, MA  Room For All  rmforall@comcast.net
505-501-2298  1943 Otowi Road   Santa Fe, New Mexico 87505

http://groups.yahoo.com/group/aspartameNM/messages
group with 73 members, 1,339 posts in a public, searchable archive
http://RMForAll.blogspot.com  http://AspartameNM.blogspot.com
*******************************************************

From: "David Wallinga" <dWallinga@IATP.ORG>
To: <Occ-Env-Med-L@MC.DUKE.EDU>
Subject: Obfuscation of The Iatrogenic Autism Epidemic__Pediatrics
letter
Date: Wednesday, May 10, 2006 1:49 PM

---------------------- Information from the mail header
----------------
Sender:
Occupational & Environmental Medicine for Clinicians & Public
Health Professionals <Occ-Env-Med-L@MC.DUKE.EDU>
Poster:       David Wallinga <dWallinga@IATP.ORG>
Subject:  Obfuscation of
The Iatrogenic Autism Epidemic__Pediatrics letter
------------------------------------------------------------------------

Dear Colleagues:

This provocative letter in Pediatrics is sure to cause some healthy
discussion

EXCERPT: "No controlled, randomized study regarding the safety of
amalgam or ethylmercurithiosalicate exists."

http://pediatrics.aappublications.org/cgi/eletters/117/4/1028

The Obfuscation of The Iatrogenic Autism Epidemic
Kenneth P. Stoller, Pediatrician, International Hyperbaric Medical
Assoc., in the current Journal of American Academy of Pediatrics.
info@hbotnm.com
(5 May 2006) Pediatrician, Post peer-review letter.

     UW-Madison researcher Paul Shattuck concludes that special
International Hyperbaric education figures being used are "faulty and
do
not substantiate such a claim" (that there is an autism epidemic). Paul
Shattuck seems to be saying that all the reported autistic children
have
always been here, they were just called something else. (Paul T.
Shattuck: The Contribution of Diagnostic Substitution to the Growing
article Administrative Prevalence of Autism in US Special Education,
Pediatrics 2006; 117: 1028-1037)

     As a pediatrician, who has been in practice for over two decades,
I find it more than a little insulting as well as disturbing to have
someone say that these children were always there.
As a scientist, I find the current approach to the autism epidemic -
"The Emperor's New Clothes" approach - to be deeply disturbing.
For years the vaccine division at the CDC and others have said
the reason for the dramatic increase in autism
is due to "better diagnosing" and "greater awareness."
They have encouraged those like Paul Shattuck
to manufacture uncertainty.
Nevertheless, with eighty percent of autistic Americans
under the age of 18, we will see, clothes and all,
a dramatic impact on Social Security in coming years
as these children become dependent adults.
There are no studies that have found the previously undiagnosed
or misdiagnosed autistic individuals among older Americans.
They simply aren't there.

     We need to address the real reason for the alarming autism rate.
No more secrets or truth-spinning.
This is not a faux epidemiological epidemic, nor an infectious
epidemic,
nor a genetic epidemic (as there are no genetic epidemics).
That leaves an epidemic linked to some sort of exposure.
Now, the increase of autism has been linked to the increase
in mercury exposure through fish and industrial sources,
amalgam and additionally, through increased parenteral exposure to
ethylmercurithiosalicate.
No controlled, randomized study regarding the
safety of amalgam or ethylmercurithiosalicate exists.

     A recent study, using infant Macaca fascicularis primates
exposed to injected ethylmercury or those exposed to equal amounts
of ingested methylmercury,
showed that ethylmercuy was retained twice as much
inorganic mercury in their brains in comparison
to the methylmercury exposed primates.
(Burbacher T, et al.
Comparison of blood and brain mercury levels in infant monkeys
exposed to methylmercury or vaccines containing thimerosal.
Environmental Health Perspectives, 2005 Aug: 113(8): 1015-21.)
These primates were exposed to mercury levels at a rate equal
to what children in the United States received via standard
childhood vaccines from 1991- 2003.

     Cysteine and glutathione synthesis are crucial for mercury
detoxification, and are reduced in autistic children,
possibly due to epigenetic polymorphisms.
(Deth, R.C.: Truth revealed:
New scientific discoveries regarding mercury in medicine and autism.
Congressional Testimony before the U.S. House of Representatives.
Subcommittee on human rights and wellness, Sept. 8. 2004,
Waly M et al: Activation of methionine synthase by insulin-like
growth factor1 and dopamine: a target for neurodevelopmental
toxins and thimerosal. Mol. Psychiatry 9, 358-370 2004).

     Therefore, autistic children have 20% lower levels of cysteine
and
54% lower levels of glutathione, which adversely affect their ability
to
detoxify and excrete metals like mercury.
(James, S.J. et al.:
Metabolic biomarkers of increased oxidative stress and impaired
methylation capacity in children with autism.
Am. J. Clin. Nutr. 80, 1611-1617 2004).
This leads to a higher concentration of free mercury in blood,
which then transfers into tissues and increases the half-life of
mercury
in the body, as compared to children
with normal levels of cysteine and glutathione.

As was shown by Bradstreet et al
(Bradstreet, J et al.:
A case control study of mercury burden in children
with autistic spectrum disorders. J. Am. Phys. Surg. 8, 76-79 2003)
in a study involving 221 autistic children,
vaccinated autistic children showed about 6 fold
elevation of urinary mercury than normal controls after appropriate
mobilization with the chelating agent DMSA.

     Delayed detoxification of mercury severely impairs methylation
reactions (required for the correct expression of DNA, RNA, and
neurotransmitters), which further adversely affects growth factor
derived development of the brain and attention abilities.
Phospholipid methylation, which is crucial for attention,
is impaired in autistic and attention deficit hyperactivity disorders.
Ethyl mercury levels, seen ten days after vaccination
(Pichichero et al:
Mercury concentrations and metabolism in infants
receiving vaccines containing thiomersal: a descriptive study.
Lancet 360, 1737-1741 2002)
with ethylmercurithiosalicate doses lower than what infants received
during the 1990s, produced greater than 50% inhibition of methylation.

     In vitro studies have shown that ethylmercurithiosalicate was
more
than 100-fold more potent than inorganic mercury in inhibiting such
essential methylation reactions.
Inorganic mercury was found to be 10 fold more potent than lead
in inhibition of neuronal microtubule.
(Stoiber, T et al.:
Disturbed microtubule function and induction of micronuclei
by chelate complexes of mercury(II).
Mutat. Res. 563, 97-106 2004;
Thier, R et al.: Interaction of metal salts with cytoskeletal
motor protein systems. Toxicol. Lett. 140141, 75-81 2003).

Inorganic mercury also leads to growth inhibition and denudation of
neuronal growth cones.
(Leong, C.C. et al:
Retrograde degeneration of neurite membrane structural integrity
of nerve growth cones following in vitro exposure to mercury.
Neuroreport 12, 733-737).

     It was also shown that concentrations of
ethylmercurithiosalicate,
which can occur after vaccination, induce membrane and DNA
damage and initiate apoptosis in human neurons.
(Baskin, D.S. et al:
Thimerosal induces DNA breaks, caspase3 activation, membrane
damage, and cell death in cultured human neurons and fibroblasts.
Toxicol. Sci. 74, 361-368 2003).

     It has been estimated that about 15% of the population may show
enhanced susceptibility to mercury exposure.
Levels of ethyl mercury found 8 days after vaccination leads
to 50% inhibition of methionine synthase (MS).
Compounding this toxic sequelae of ethylmercurithiosalicate,
neurons are unable to synthesize cysteine, the rate limiting amino acid
for glutathione synthesis.
Thus, neurons are most sensitive to mercury toxicity
since glutathione is the major intracellular agent in mercury
and heavy metal detoxification.
It is known that ethylmercurithiosalicate and inorganic mercury
depletes intracellular glutathione levels,
which subsequently leads to oxidative stress, neuronal cytotoxicity
and death.

     In vitro studies suggest that the neurotoxicity of
ethylmercurithiosalicate is enhanced through
neomycin and aluminium hydroxide (ingredients in vaccines) and
testosterone, while estrogen decreases the toxic effects.
Estrogen has been shown to decrease the toxicity of inorganic
mercury which may explain the 4 to 1 ratio of boys to girls in autism.
Lead may play a synergistic pathogenetic role in neurodevelopment
disorders and autism.
Combination of lead and mercury resulted in an increase of toxicity in
vitro.

     In a first analysis of the VSD datasets,
Verstraeten et al had described a 7.6 to 11.4 fold increase of autism
risk in children at one month,
with the highest mercury exposure levels compared to children
with no exposure.
In four subsequent separate generations of the analysis,
which involve the exclusion of children with no
ethylmercurithiosalicate exposure and less than two polio vaccines,
the statistical significance disappeared.

     Ethylmercurithiosalicate was tested only once, by Eli Lilly on 22
adult patients suffering from meningitis.
There was no chance for follow-up to observe long-term effects,
as all of the patients in this "study" died.
Even if follow-up had been possible, damage to the developing brains
of very young children would have remained an unknown.

Eli Lilly said it was safe and the medical community accepted it.
After the creation of the FDA, its use was simply continued.
The federal government has never tested the type of mercury
in vaccines for toxicity.
This is an unconscionable oversight failure at best,
at worse it is an example that we have left consensus reality
to be created by the liars, thieves, cheats, killers,
and the PR junk scientists they employ.

    So, here we have a real problem, autism affecting 1 in 166
or even more -- where is the public funding?
Where is the public outcry? Where is the response from academia?
There isn't any!

But in the case of bird flu, with no real evidence that the H5N1
virus is a health problem for humans that do not have the most
intimate contact with birds combined
with a compromised immune system,
billions of dollars have been allocated to clothe this "Emperor."

      We have troubling glimpses, in the press, of the brand-new
bird-flu containment plan the White House is laying out as detailed
in an April 16 Washington Post piece by Ceci Connolly,
"U.S. Plan For Flu Pandemic Revealed,
Multi-Agency Proposal Awaits Bush's Approval."

"...Experts project that the next pandemic -- depending on severity
and countermeasures -- could kill 210,000 to 1.9 million Americans.
National Guard troops could be dispatched to cities facing possible
`insurrection,' said Jeffrey W. Runge, chief medical officer at the
Department of Homeland Security. ...The federal government -- as
well as private businesses -- should expect as much as 40 percent
of its workforce to be out during a pandemic, said Bruce Gellin,
director of the National Vaccine Program Office at HHS.
Some will be sick or dead; others could be depressed or caring
for a loved one or staying at home to prevent spread of the virus.
The problem is, you never know which 40 percent will be out,' he said."

      Putting down INSURRECTIONS, no more Bills Of Rights for the
duration of the "pandemic." Chaos! Madness! Protect government
workers first and foremost. All based on ZERO scientific evidence,
all this is swinging into gear. April 15, two days before the above
Washington Post article, an article in the Tacoma Tribune by M.A. Otto.
It reports on a public-health conference in downtown Tacoma,
with featured speaker, Julie Gerberding, the head of the CDC.
`There is no evidence it will be the next pandemic,' Dr. Julie
Gerberding,
head of the Centers for Disease Control and Prevention in Atlanta,
said of avian flu. There is `no evidence it is evolving in a direction
that
is becoming more transmissible to people.'" "
Gerberding's comments on bird flu contrast
earlier statements from the federal government
that tended to emphasize worse-case scenarios."

     So, there is no evidence of a pandemic, but thank you for the $7
billion anyway?

     We are living in a time where an incredible overplay and lies and
self-aggrandizing behavior and non-science is the norm.
Autism is a real problem, not a potential problem.
We have tolerated the junk science
that has covered up the true cause of this epidemic at a considerable
cost to science, the public, and our very way of life in this country.
Is it stretch to realize that by putting our heads in the sand about
the
autism epidemic we have made it possible for the groundwork
to be put in place for Marshal [Martial] Law?

     Not something easy to contemplate? Then ask why haven't
pediatricians come forward to demand the end of the use of
ethylmercurithiosalicate once and for all, and to advocate for the
treatment of these children before it is too late?

Conflict of Interest: None declared.

[Non-text portions of this message have been removed]
-----------------------
David Wallinga, MD, MPA
Director, Food and Health Program
Institute for Agriculture and Trade Policy
2105 First Avenue South  Minneapolis, MN 55404
dwallinga@iatp.org  612-870-3418
www.iatp.org/foodandhealth
*******************************************************

http://groups.yahoo.com/group/aspartameNM/message/1243
rationale to ban thimerosal (mercury) in vaccines and to ban aspartame
(methanol, formaldehyde), speech from Kenneth P Stoller, MD
to New Mexico Board of Pharmacy: Murray 2005.11.10

http://www.prweb.com/releases/2005/11/prweb308566.php

November 10, 2005

New Mexico Board of Pharmacy to Hear Petition to Limit Exposure to
Aspartame and Thimerosal

Santa Fe, NM (PRWEB) November 10, 2005 -- Dr. Kenneth Stoller,
Santa Fe Pediatrician and Clinical Assistant Professor of Pediatrics at
the University of New Mexico, School of Medicine,
has released the text of his remarks
to be made on November 14th 2005, at the New Mexico
Board of Pharmacy's next meeting.

He is requesting that the New Mexico Board of Pharmacy issue an
immediate advisory so that all New Mexicans who desire to receive the
current flu vaccine receive information about what is being injected in
terms of the amount of neurotoxic mercury in the vaccine, which is a
labeling omission, and thus a violation of the New Mexico Drug Act
(NMSA 2-1-9). Stoller further requests that the New Mexico Board of
Pharmacy prohibit the use of this flu vaccine containing thimerosal to
all
New Mexico pregnant woman and children under 50 lbs.....
*******************************************************

The Comet assay can quickly show whether aspartame or its body
products (methanol, formaldehyde, formic acid -- the same as in
hangovers from dark wines and liquors) are genotoxic:
Murray 2006.05.09

http://groups.yahoo.com/group/aspartameNM/message/1337
Comet assay finds DNA damage from sucralose, cyclamate, saccharin,
aspartame in mice: Sasaki YF & Tsuda S  Aug 2002:
Murray 2006.05.08

[ 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.  Methanol is the only component of aspartame that
can lead to DNA damage. ]

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

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  [A detailed look at the data]     ]

http://groups.yahoo.com/group/aspartameNM/message/1106
hangover research relevant to toxicity of 11% methanol in aspartame
(formaldehyde, formic acid): Calder I (full text): Jones AW:
Murray 2004.08.05 rmforall

Since no adaquate data has ever been published on the exact
disposition of toxic metabolites in specific tissues in humans of the
11% methanol component of aspartame, the many studies on
morning-after hangover from the methanol impurity in alcohol drinks
are the main available resource to date.

Jones AW (1987) found next-morning hangover from red wine with
100 to 150 mg methanol
(9.5% w/v ethanol, 100 mg/l methanol, 0.01%,
one part in ten thousand).

http://groups.yahoo.com/group/aspartameNM/message/1100
research on aspartame (methanol, formaldehyde, formic acid) toxicity:
Murray 2004.07.19 rmforall

http://groups.yahoo.com/group/aspartameNM/message/1286
methanol products (formaldehyde and formic acid) are main cause of
alcohol  hangover symptoms [same as from similar amounts of
methanol, the 11% part of aspartame]: YS Woo et al, 2005 Dec:
Murray 2006.01.20

Addict Biol. 2005 Dec;10(4): 351-5.
Concentration changes of methanol in blood samples during
an experimentally induced alcohol hangover state.
Woo YS, Yoon SJ, Lee HK, Lee CU, Chae JH, Lee CT, Kim DJ.
Chuncheon National Hospital, Department of Psychiatry,
The Catholic University of Korea, Seoul, Korea.
http://www.cuk.ac.kr/eng/  sysop@catholic.ac.kr
Songsin Campus: 02-740-9714   Songsim Campus: 02-2164-4116
Songeui Campus: 02-2164-4114
http://www.cuk.ac.kr/eng/sub055.htm  eight hospitals

[  Han-Kyu Lee ]

A hangover is characterized by the unpleasant physical and mental
symptoms that occur between 8 and 16 hours after drinking alcohol.
After inducing experimental hangover in normal individuals,
we measured the methanol concentration prior to
and after alcohol consumption
and we assessed the association between the hangover condition
and the blood methanol level.

A total of 18 normal adult males participated in this study.
They did not have any previous histories of psychiatric
or medical disorders.

The blood ethanol concentration prior to the alcohol intake
(2.26+/-2.08) was not significantly different from that
13 hours after the alcohol consumption (3.12+/-2.38).

However, the difference of methanol concentration
between the day of experiment (prior to the alcohol intake)
and the next day (13 hours after the alcohol intake)
was significant (2.62+/-1.33/l vs. 3.88+/-2.10/l, respectively).

[ So, the normal methanol level was 2.62 mg per liter,
and increasing that by 50% = 1.3 mg per liter to 3.88 mg per liter
caused hangover symptoms.  The human body has about
5.6 liters blood, so adding 1.3 mg per liter gives an estimate
of 7.3 mg added methanol, as much as 4 oz diet soda.

Diet soda is about 200 mg aspartame per 12 oz can,
which is 22 mg (11% methanol), 1.83 mg methnol per ounce.

This suggests that alcohol drinkers are more sensitive to methanol
than the average diet soda drinker, some of whom find symptoms
from a third of a diet soda.]

A significant positive correlation was observed
between the changes of blood methanol concentration
and hangover subjective scale score increment when covarying
for the changes of blood ethanol level (r=0.498, p<0.05).

This result suggests the possible correlation of methanol
as well as its toxic metabolite to hangover.  PMID: 16318957
[ The "toxic metabolite" of methanol is formaldehyde, which in turn
partially becomes formic acid -- both potent cumulative toxins
that are the actual cause of the toxicity of methanol.]
*******************************************************

http://groups.yahoo.com/group/aspartameNM/message/1100
research on aspartame (methanol, formaldehyde, formic acid) toxicity:
Murray 2004.07.16

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This pathway contributes to a long-term unobserved compartment.

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

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

it can further be calculated that 48 h following the start
of a 2-h inhalation exposure to 900 ppm of 14C-methanol vapors
in female cynomolgus monkeys,
only 23% of the absorbed 14C-methanol was eliminated from the body.

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

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

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

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

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

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

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

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

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

http://www.toxsci.oupjournals.org/cgi/content/full/64/2/169  full text

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

BIOTRANSFORMATION AND TOXICOKINETIC

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

Michèle Bouchard *, #,  michele.bouchard@umontreal.ca

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

Pierre-Olivier Droz, #

and Gaétan Carrier*   gaetan.carrier@umontreal.ca

* Department of Environmental and Occupational Health,
Faculty of Medicine, Université de Montréal, P.O. Box 6128,
Main Station, Montréal, Québec, Canada, H3C 3J7
Fax: (514) 343-2200

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

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

http://groups.yahoo.com/group/aspartameNM/message/1328
migraine from sucralose, Bigal ME & Krymchantowski AV,
Headache 2006 March; formaldehyde from 11% methanol part of
aspartame or from red wine causes same toxicity (hangover) harm:
Murray 2006.05.04

http://groups.yahoo.com/group/aspartameNM/message/1329
aspartame or MSG affects circadian rhythms in rats, two studies,
P. Subramanian, T. Manivasagam et al 2004:
Murray 2006.04.27

Dark wines and liquors, as well as aspartame, provide
similar levels of methanol, above 120 mg daily, for
long-term heavy users, 2 L daily, about 6 cans.

Within hours, methanol is inevitably largely turned into formaldehyde,
and thence largely into formic acid --  the major causes of the dreaded
symptoms of "next morning" hangover.

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, 37 mg,
is 18.5 times the USA EPA limit for daily formaldehyde in
drinking water, 2.0 mg in 2 L average daily drinking water.

Any unsuspected source of methanol, which the body always quickly
and largely turns into formaldehyde and then formic acid, must be
monitored, especially for high responsibility occupations, often with
night shifts, such as pilots and nuclear reactor operators.

http://groups.yahoo.com/group/aspartameNM/message/1279
all three aspartame metabolites harm human erythrocyte [red blood cell]
membrane enzyme activity, KH Schulpis et al, two studies in 2005,
Athens, Greece, 2005.12.14: 2004 research review, RL Blaylock:
Murray 2006.01.14

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@atlas.uoa.gr;
K.H. Schulpis inchildh@otenet.gr; G.J. Reclos reklos@otenet.gr;

http://groups.yahoo.com/group/aspartameNM/message/1271
combining aspartame and quinoline yellow, or MSG and brilliant blue,
harms nerve cells, eminent C. Vyvyan Howard et al, 2005
education.guardian.co.uk, Felicity Lawrence: Murray 2005.12.21

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

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

http://groups.yahoo.com/group/aspartameNM/message/1189
Michael F. Jacobson of CSPI now and in 1985 re aspartame toxicity,
letter to FDA Commissioner Lester Crawford;
California OEHHA aspartame critique 2004.03.12;
Center for Consumer Freedom denounces CSPI: Murray 2004.07.27
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http://www.efsa.eu.int/press_room/press_release/1472_en.html
http://www.efsa.eu.int/science/afc/afc_opinions/1471_en.html
http://www.efsa.eu.int/science/afc/afc_opinions/1471/afc_op_ej356_aspartame_en1.pdf

I watched the EFSA video carefully.   I've been studying their
44-page review with surprise this afternoon.  Basically, their list of
serious faults in the Ramazzini work, including the 2002 studies on
methanol and formaldehyde, is devastating and justified.
Most of the Ramazzini claims about the carcinogenity of aspartame in
rats are worthless.
However, their report of very low levels of cancers in the peripheral
nerves and brain to my eyes, as a medical laymen, still seems to stand
up at least as guides for more research that must be done quickly:

Page 25

"In relation to the malignant schwannomas of the peripheral nerves
observed in the study, the Panel notes the statistically significant
positive trend (p<0.05) in males, and the pattern of incidence in
females, in which nine malignancies were observed among treated
animals of the different dosage groups and none among the controls.

However, the numbers of tumours were low, the dose-response
relationship, while showing a positive statistical trend in males,
was very flat over a wide dose range and there is also uncertainty
about the diagnosis of these tumours.

The Panel notes that 12 malignant brain tumours (10 gliomas,
1 medulloblastoma and 1meningioma) were observed in male
and female aspartame-treated groups,
whereas none were observed in controls.

Since there was no dose-response relationship for these tumours
the Panel does not consider the administration of aspartame
responsible for their occurrence."

I suggest that some rats may have genetic factors that are triggered by
very low levels of methanol-derived chemicals to set off specific
rare cancers, in which case the results will be dose independent, just
as a match or a blowtorch will have the effect on a single fuse to a
bomb.  It may be that something like this is already known to science.

It is important not to demonize the EFSA.

In mutual service,  Rich

Aspartame, The EFSA Journal (2006) 356, p. 40-42 of 44

"In monkeys given 3 g of MeOH/kg bw
(750 times higher than available from aspartame at its ADI level)
formaldehyde could be detected in the blood
at a level of 27 - 45 microM over the period of 18 hrs
following dosing with methanol.

No formaldehyde could be found in liver, kidney, urine
or several neural tissues
(LOD 25 microM; ~ 0.75  mg/L or 0.75 mg/kg tissue).

Formic acid was readily detected in all tissues and body fluids
studied,
in particular in urine, liver, blood, and kidney (McMartin et al.,
1979)."

"In rats,
~40% and in monkeys about 30% of the dose was not accounted for,
but it is noted that residual radioactivity in the carcass
was not further studied.
These studies were done with
dose levels of 10 to 20 mg aspartame/kg bw (Oppermann, 1984).

Recently it has been demonstrated that when [14C-methyl]-aspartame is
administered to rats in a single oral dose level of 0.68 mmol/kg bw
(~ 20 mg/kg bw) in liver, kidney and plasma
about 0.1 - 0.4% of the dose/g tissue.
In particular in blood (0.1-0.2%/g tissue)
about 98% of the radioactivity was bound to protein
and in liver about 78% was bound to protein / nucleic acids.

Radioactivity was also found in protein of other tissues such as
kidney (level about the same as in plasma), muscle, brain, cornea,
retina and white and brown adipose tissue
(each one order of magnitude less than plasma).

The nature of the bound radioactivity was further studied in the liver.
The authors speculated that the bound radioactivity
resulted from the formation of formaldehyde from the 14C-MeOH,
because neither with MeOH nor with formate could covalent binding
be demonstrated in direct labelling experiments.

The exact nature of the radioactivity incorporated in proteins and
nucleic acids was not elucidated.
The chromatographic properties of their hydrolysis products
(i.e. free amino acids and free DNA and RNA bases) were compared
to those of normal amino acids and based on observed differences,
it was speculated that the incorporated radioactivity
did not result from 1-carbon pathways (i.e. tetrahydrofolate pathways)
but rather from direct formaldehyde adduct formation
(Trocho et al., 1998).

The study of Trocho et al. (1998) has been heavily criticised by Tephly
(1999), who argues that neither methanol itself nor formaldehyde
will reach the systemic circulation after oral exposure.

The adducts in the study by Trocho et al. were not identified with
certainty and adduct formation of 14C-methanol or 14C-formaldehyde
were not studied in vivo for reasons of comparison.

The very low amount of incorporation of 14C from
[14C-methyl]-aspartame into tissue macro molecules was thought
to be totally accounted for by the 1-carbon tetrahydrofolate pathway.

However, Tephly (1999) did not comment on Trocho et al.'s finding
of the aberrant chromatographic properties of the protein
and nucleic acid hydrolysis products
as compared to those of corresponding standards
(i.e. free amino acids and nucleic acid bases).

It has also been argued that formaldehyde forms
DNA protein cross-links (MAK, 2002)
and that it reacts spontaneously with albumin (Tephly, 1999).
This would at least explain findings of radioactive "adducts"
in liver and plasma of animals dosed with aspartame
(Trocho et al., 1998).

In addition, MAK (2002) have also argued that it is very difficult to
study adduct formation of formaldehyde because of the efficient
incorporation of this substance in 1-carbon pathways."

http://groups.yahoo.com/group/aspartameNM/message/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

http://ww.presidiotex.com/barcelona/index.html  full text
Formaldehyde derived from dietary aspartame
binds to tissue components in vivo.
Life Sci June 26 1998; 63(5): 337-49.
Departament de Bioquimica i Biologia Molecular,
Facultat de Biologia, Universitat de Barcelona, Spain.
http://www.bq.ub.es/cindex.html    Línies de Recerca: Toxicitat de
l'aspartame     http://www.bq.ub.es/grupno/grup-no.html
Sra. Carme Trocho, Sra. Rosario Pardo, Dra. Immaculada Rafecas,
Sr. Jordi Virgili, Dr. Xavier Remesar,  Dr. Jose Antonio
Fernandez-Lopez, Dr. Marià Alemany [male]
Fac. Biologia Tel.: (93)4021521, FAX: (93)4021559
Sra. Carme Trocho "Trok-ho"  Fac. Biologia Tel.:   (93)4021544,
FAX: (93)4021559
alemany@porthos.bio.ub.es  bioq@sun.bq.ub.es  josefer@porthos.bio.ub.es
rafecas@porthos.bio.ub.es  remesar@porthos.bio.ub.es

Abstract:
Adult male rats were given an oral dose of 10 mg/kg aspartame,
14C-labeled in the methanol carbon.
At timed intervals of up to 6 hours, the radioactivity in plasma and
several organs was investigated.
Most of the radioactivity found (>98% in plasma, >75% in liver)
was bound to protein.
Label present in liver, plasma and kidney was in the range of 1-2%
of total radioactivity administered per g or mL, changing little with
time.
Other organs (brown and white adipose tissues, muscle, brain, cornea
and retina) contained levels
of label in the range of 1/12th to 1/10th of that of liver.
In all. the rats retained, 6 hours after administration,
about 5% of the label, half of it in the liver.

The specific radioactivity of tissue protein, RNA and DNA
was quite uniform.
The protein label was concentrated in amino acids, different from
methionine, and largely coincident with the result of protein exposure
to
labeled formaldehyde.
DNA radioactivity was essentially in a single different adduct base,
different from the normal bases present in DNA.
The nature of the tissue label accumulated was, thus,
a direct consequence of formaldehyde binding to tissue structures.

The administration of labeled aspartame to a group of cirrhotic rats
resulted in comparable label retention by tissue components,
which suggests that liver function (or its defect) has little effect on
formaldehyde formation from aspartame
and binding to biological components.
The chronic treatment of a series of rats with 200 mg/kg of non-labeled
aspartame during 10 days results in the accumulation of even more label
when given the radioactive bolus,
suggesting that the amount of formaldehyde adducts coming from
aspartame in tissue proteins and nucleic acids may be cumulative.

It is concluded that aspartame consumption may constitute a hazard
because of its contribution to the formation of formaldehyde adducts.
PMID: 9714421

http://groups.yahoo.com/group/aspartameNM/message/1067
eyelid contact dermatitis by formaldehyde from aspartame,
AM Hill & DV Belsito, Nov 2003: Murray 2004.04.04 [ 150 KB ]

[ includes this brief review of McMartin, 1979]

"For the methanol sensitive, folate-deficient monkey A,
the  assay used was the chromatropic acid method,
with a detection limit  of .025 mmol/L.
None of the five tissues showed any formaldehyde with this assay,
except the midbrain, 0.14 mmol/kg wet weight tissue
[ units converted from their 0.14 micromole/gm ]--  just 1.5 times
the detection limit of .09 mmol/kg wet tissue weight (given on p.
648)."

Biochemical Pharmcacology 1979: 28; 645-649.
Lack of a role for formaldehyde in methanol poisoning in the monkey.
Kenneth E. McMartin, Gladys Martin-Amat, Patricia E. Noker
and Thomas R. Tephly
The Toxicology Center, Dept. of Pharmacology,
University of Iowa, Iowa City, Iowa 52242
K.E. McMartin and T.R. Tephly, authors of many pro-aspartame
studies, in Biochemical Pharmacology (1979) remarked,
"It is now generally accepted that the toxicity of methanol
is due to the formation of toxic metabolites,
either formaldehyde or formic acid."
They put damage doses of methanol into the stomachs
of three monkeys, and, using insensitive tests, found no
formaldehyde in many tissues -- except
for a single datum in the midbrain, 1.5 times the detection limit.
They did report  widespread accumulation of formic acid in five
tissues.
The use of inadequate tests is common in industry research
that is funded to claim the safety of profitable toxins.
Since then, industry scientists have been very wary of doing studies
on primates, which all too easily show the dangers to humans.

"Abstract [ not given in PubMed ]:
[ My briefer comments are in square brackets. ]
Methanol was administered [ by nasogastric tube ] either to untreated
cynomolgus monkeys [ 2-3.5 kg ]
or to a folate-deficient cynomolgus monkey
which exhibits exceptional sensitivity to the toxic effects of
methanol.
Marked formic acid accumulation in the blood
and in body fluids and tissues was observed.
No formaldehyde accumulation was observed in the blood
and no formaldehyde was detected in the urine, cerebrospinal fluid,
vitreous humor, liver, kidney, optic nerve, and brain in these monkeys
at a time when marked metabolic acidosis
and other characteristics of methanol poisoning were observed.
Following intravenous infusion into the monkey,
formaldehyde was rapidly eliminated from the blood with a half-life
of about 1.5 min and formic acid levels promptly increased in the
blood.
Since formic acid accumulation accounted for the metabolic acidosis
and since ocular toxicity essentially identical to that produced in
methanol poisoning has been described after formate treatment,
the predominant role of formic acid as the major metabolic agent
for methanol toxicity is certified.
Also, results suggest that formaldehyde is not a major factor in
the toxic syndrome produced by methanol in the monkey."

"It is now generally accepted that the toxicity of methanol is due to
the
formation of toxic metabolites (1,2), either formaldehyde or formic
acid."

So, this is an acute toxicity study, with little relevance for chronic
long-term, low-level exposure.

Monkeys, like people, are susceptible to methanol toxicity.

This team cites their six previous methanol in monkey studies,
from 1975 to 1977.

The report is difficult to understand,
since the three monkeys were treated differently,
and different assays were used.

For the methanol sensitive, folate-deficient monkey A,
the  assay used was the chromatropic acid method,
with a detection limit  of .025 mmol/L.
None of the five tissues showed any formaldehyde with this assay,
except the midbrain, 0.14 mmol/kg wet weight tissue
[ units converted from their 0.14 micromole/gm ]-- just 1.5 times
the detection limit of .09 mmol/kg wet tissue weight (given on p. 648).
[ Since 1 kg of water is 1 L, 1 mmol/kg is equivalent to 1 mmol/L. ]

Meanwhile, in the methanol sensitive, folate-deficient monkey A,
the blood formate level rose by 18 hours from  0.18 to 10.02 mEq/L.
[ I assume that a mEq is equivalent to a mmol-- let me
know if I'm wrong. ]
The formate detection limits for the assays were not given in this
report.
The formate level in the vitreous humor of the eye of monkey A
was 7.90 mEq/L.
It is well known that formate is extremely damaging to the eye.
For unexplained reasons, formate levels in the five tissues
and cerebrospinal fluid were not
measured in the methanol sensitive, folate-deficient monkey A., i
n the cerebrospinal fluid of monkey B,
or in the optic nerve of monkey C.
Formaldehyde was not measured in the optic nerve of Monkey A.
The kidney formate level for monkey B was 6.33
and for C was only 0.44, with no comment or explanation given.

The experiment seems arbitrary, capricious, and erratic.

For monkey A, after 18 hours,
the urine formaldehyde level was below detection level,
while urine formate was 115.80 mEq/L --  so much of the
formaldehyde had been converted into formic acid,
another cumulative, potent toxin.

"In the presence of high formate values and definitive evidence
of toxicity in methanol-poisoned monkeys,
no measurable formaldehyde was found in the
body tissues that were tested."

It is reasonable to surmise that more sensitive assays
would have found formaldehyde and formate bound to
and reacted with a variety of cellular substances in all tissues --
just
as the 1998 Trocho study confirmed. (Appendix E)

Monkeys B and C were normal, not extra vulnerable to methanol,
and were given 3,000 mg/kg methanol, and samples taken at 18 hr.
Formaldehyde was detected only in the blood of Monkey B,
while formate was found in 8 and 10, respectively, of the 10 fluid
and tissue samples in Monkeys B and C.
For instance, the lowest value of formate,
except for zero-time blood, for each monkey was in the midbrain,
2.16 mmol/kg for Monkey B
(24 times the detection limit for the chromatropic acid method)
and 1.02 mmol/kg (1.3 times the detection for the dimedon method)
for Monkey C.
This shows accumulation of formate in liver, kidney, optic nerve,
cerebrum, and midbrain.

"Thus, whereas one can associate formate intimately
with ocular toxicity in the monkey, no association of formaldehyde
with ocular toxicity can be made at this time.
It is not possible to completely eliminate formaldehyde as a
toxic intermediate because formaldehyde could be formed
slowly within cells and interfere with normal cellular function
without ever obtaining levels that were detectable in body fluids..."

"Acknowledgements-- This research was supported
by NIH grant GM 19420
and GM 12675."  [not funded by the industry]
*******************************************************