http://groups.yahoo.com/group/aspartameNM/message/936
flawed test for aspartame DNA damage: Jeffrey & Williams 2000: Murray:
1.3.3 rmforall:
FDA Docket 02P-0317 Recall Aspartame as a Neurotoxic Drug

Please post this to the FDA Dockets website.

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

The flaw is that aspartame itself, exposed directly to cells in a lab,
is not very reactive. However, soon after ingestion by a creature, its
11% methanol component is released and quickly metabolized into the
potent, cumulative, mutagenic toxicants, formaldehyde and formic acid.
When Oyama (2002) tested formaldehyde directly on rat cells, 1 mmol/L
formaldehyde was found to cause damage.

http://groups.yahoo.com/group/aspartameNM/message/885
aspartame, methanol, formaldehyde, formate toxicity on rat cells:
Oyama, Akaike, et al, Jan 2002: Murray 11.7.2 rmforall

I suspect that the Jeffrey & Williams study, their only one on
aspartame, was funded by the industry.
**********************************************************************

Food Chem Toxicol 2000 Apr;38(4):335-8
Lack of DNA-damaging activity of five non-nutritive sweeteners in the
rat hepatocyte/DNA repair assay.
Jeffrey AM, Williams GM.
New York Medical College, Department of Pathology, Basic Sciences
Building, Valhalla, NY 10595, USA.

The non-nutritive sweeteners acesulfame-K, aspartame, cyclamate,
saccharin and sucralose were tested for DNA damaging activity in the
rat hepatocyte/DNA repair assay.

Using hepatocytes from F344 and Sprague-Dawley male rats, all were
inactive despite strong responses for the positive control,
2-aminofluorene. PMID: 10722887
***********************************************************************

http://groups.yahoo.com/group/aspartameNM/message/935
comet assay finds DNA damage from sucralose, cyclamate, saccharin in
mice: Sasaki YF & Tsuda S Aug 2002: Murray 1.1.3 rmforall

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

.....four sweeteners (sodium cyclamate, saccharin, sodium saccharin, and
sucralose) also induced DNA damage in gastrointestinal organs....

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

[ Aspartame, neotame, acesulfame-K, and stevia should be tested
immediately. ]

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

Jeffrey AM has 78 items in PubMed since 1969. while Williams GM has
many-- there seem to be other scientists with the same name.

http://www.nymc.edu/

Alan M. Jeffrey, Ph.D. Pathology Faculty
Carcinogenesis, DNA adducts, Toxicology

http://www.nymc.edu/fhp/wms/indview.asp

Research Professor, Department of Pathology
amj1@...
Dept. of Pathology
Basic Sciences Building, New York
Medical College
Valhalla, NY 10595

1970 - 1974 NIAMDD, NIH, Bethesda, MD.; Laboratory of Chemistry,
Visiting Fellow (1970-1972); Laboratory of Biochemical Pharmacology,
Visiting Associate (1972-1974).
1974 - 1979 Institute of Cancer Research, Columbia University, New
York, NY.; Research Associate (1974-1976); Senior Research Associate
(1976-1979).
1979 - present Division of Environmental Sciences. Current position:
Adjunct Associate Professor, Clinical Public Health.
1996 - 2000 American Health Foundation, Naylor Dana Institute,
Valhalla, NY. Research Scientist; Head, Genetic Toxicology.
2000 - present New York Medical College, Valhalla, NY. Research
Professor.

Professional Interests:
Currently working on ³²P-postlabeling analysis of DNA and gc/ms of
protein and DNA adducts aimed at understanding mechanisms of toxicity,
especially genotoxicity and carcinogenicity and biomonitoring.

Gary M. Williams, M.D. Pathology Faculty
http://www.nymc.edu/fhp/wms/indview.asp
Professor, Department of Pathology
Gary_Williams@...
Dept. of Pathology
Basic Sciences Building, New York
Medical College
Valhalla, NY 10595
Professional Interests:

The research in Dr. Williams' laboratory focuses on mechanisms of
chemical carcinogenesis and procedures for identifying chemical
carcinogens. Investigations are being pursued on the pathogenesis of
liver cancer induced either by agents that attack DNA or that operate
through indirect or epigenetic mechanisms. Aspects of particular
interest are the shapes of dose - response curves for these two types
of agents, and the identification of thresholds for cellular effects.
The laboratory has a major project on interaction between ultraviolet
irradiation and chemicals to produce photochemical mutagenicity and
carcinogenicity. In studying procedures for identifying chemical
carcinogens, emphasis has been placed on techniques for measuring
interaction with DNA to detect genotoxic agents. Also under
investigation are methods for inhibiting chemical-induced
carcinogenicity.

Education Profile
Graduate Degree Medical Doctorate 1967
Graduate Degree Institution
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Undergraduate Institution
Washington and Jefferson College, Washington,
Pennsylvania. B.A. 1963; Magna Cum Laude

Eur J Cancer Prev 2002 Feb;11(1):39-48
Protective effect of acetaminophen against colon cancer initiation
effects of 3,2'-dimethyl-4-aminobiphenyl in rats.
Williams GM, Iatropoulos MJ, Jeffrey AM, Shirai T.
Department of Pathology, New York Medical University, Valhalla, NY
10595, USA. Gary_Williams@...

Drug Chem Toxicol 2002 Feb;25(1):93-107
Lack of DNA binding in the rat nasal mucosa and other tissues of the
nasal toxicants roflumilast, a phosphodiesterase 4 inhibitor, and a
metabolite, 4-amino-3,5-dichloropyridine, in contrast to the nasal
carcinogen 2,6-dimethylaniline.
Jeffrey AM, Luo FQ, Amin S, Krzeminski J, Zech K, Williams GM.
New York Medical College, Department of Pathology,
Valhalla, NY 10595, USA.

Regul Toxicol Pharmacol 2000 Dec;32(3):283-92
Oxidative DNA damage: endogenous and chemically induced.
Williams GM, Jeffrey AM.
Pathology Department, New York Medical College, Valhalla, New York
10595, USA.

A variety of types of DNA oxidation occur endogenously and mediated by
xenobiotics. Certain forms are mutagenic and carcinogenic and may lead
to other pathologies. Copyright 2000 Academic Press.
Publication Types: Review Review, Tutorial PMID: 11162722
**********************************************************************

http://groups.yahoo.com/group/aspartameNM/message/932
aspartame: methanol, formaldehyde, formic acid toxicity:
brief review: Murray 12.30.2 rmforall:

http://groups.yahoo.com/group/aspartameNM/messages
for 937 posts in a public searchable archive

It is certain that high levels of aspartame use, above 2 liters daily
for months and years, must lead to chronic formaldehyde-formic acid
toxicity, since 11% of aspartame (1,120 mg in 2L diet soda, 5.6 12-oz
cans) is 123 mg methanol (wood alcohol), immediately released into the
body after drinking (unlike the large levels of methanol locked up in
molecules inside many fruits), then quickly transformed into
formaldehyde, which in turn becomes formic acid, both of which in
time become carbon dioxide and water-- however, about 30% of the
methanol remains in the body as cumulative durable toxic metabolites of
formaldehyde and formic acid-- 37 mg daily, a gram every month.
If 10% of the methanol is retained as formaldehyde, that would give 12
mg daily formaldehyde accumulation, about 60 times more than the 0.2 mg
from 10% retention of the 2 mg EPA daily limit for formaldehyde in
drinking water.

Bear in mind that the EPA limit for formaldehyde in
drinking water is 1 ppm,
or 2 mg daily for a typical daily consumption of 2 L of water.

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

J. Nutrition 1973 Oct; 103(10): 1454-1459.
Metabolism of aspartame in monkeys.
Oppermann JA, Muldoon E, Ranney RE.
Dept. of Biochemistry, Searle Laboratories,
Division of G.D. Searle and Co. Box 5110, Chicago, IL 60680
They found that about 70% of the radioactive methanol in aspartame put
into the stomachs of 3 to 7 kg monkeys was eliminated within a day as
carbon dioxide in exhaled air and as water in the urine. They did not
mention that this meant that about 30% of the methanol must transform
into formaldehyde and then into formic acid, much of which must remain
as toxic products in all parts of the body. They did not report any
studies on the distribution of radioactivity in body tissues, except
that blood plasma proteins after 4 days held 4% of the initial
methanol. This study did not monitor long-term use of aspartame.

This long-term low-level chronic toxic exposure leads to typical
patterns of increasingly severe complex symptoms, starting with
headache, fatigue, joint pain, irritability, memory loss, and leading to
vision and eye problems and even seizures. In many cases there is
addiction. Probably there are immune system disorders, with a
hypersensitivity to these toxins and other chemicals.

Confirming evidence and a general theory are given by Pall (2002):
http://groups.yahoo.com/group/aspartameNM/message/909
testable theory of MCS type diseases, vicious cycle of nitric oxide &
peroxynitrite: MSG: formaldehyde-methanol-aspartame:
Martin L. Pall: Murray: 12.9.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/915
formaldehyde toxicity: Thrasher & Kilburn: Shaham: EPA: Gold: Murray:
Wilson: CIIN: 12.12.2 rmforall

http://www.drthrasher.org/formaldehyde_1990.html [ full text ]
Arch Environ Health 1990 Jul-Aug; 45(4): 217-23
Immune activation and autoantibodies in humans
with long-term inhalation exposure to formaldehyde.
Thrasher JD, Broughton A, Madison R.
Thrasher & Associates, Northridge, California.

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11
Embryo toxicity and teratogenicity of formaldehyde. [ 100 references]
Thrasher JD, Kilburn KH.
Sam-1 Trust, Alto, New Mexico, USA.
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html
[ 127K full text ] http://www.drthrasher.org
Jack D. Thrasher, PhD toxicology@... Sam-1 Trust,
PO Box 874 Alto, New Mexico 88312 505-336-8312 fax 425-675-7379

http://www-hsc.usc.edu/~kilburn/
Kaye H. Kilburn, M.D. kilburn@...
University of Southern California
Keck School of Medicine
Environmental Sciences Laboratory
2025 Zonal Avenue, CSC 201, Los Angeles, California 90033
text Dec, 1997 "Chemical Brain Injury"

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://groups.yahoo.com/group/aspartameNM/message/926
aspartame puts formaldehyde adducts into tissues, Part 2/2
full text, Trocho & Alemany 6.26.98: Murray 12.22.2 rmforall

http://ww.presidiotex.com/barcelona/index.html
Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X,
Fernandez-Lopez JA, Alemany M ["Trok-ho"]
Formaldehyde derived from dietary aspartame binds to tissue
components in vivo. Life Sci 1998 Jun 26; 63(5): 337-49.
Departament de Bioquimica i Biologia Molecular, Facultat de Biologia,
Universitat de Barcelona, Spain.
http://www.presidiotex.com/barcelona/index.html
Maria Alemany, PhD (male) alemany@...

http://groups.yahoo.com/group/aspartameNM/message/864
Murray: Butchko, Tephly, McMartin: Alemany: aspartame formaldehyde
adducts in rats 9.8.2 rmforall
Prof. Alemany vigorously affirms the validity of the Trocho study
against criticism:
Butchko, HH et al [24 authors], Aspartame: review of safety.
Regul. Toxicol. Pharmacol. 2002 April 1; 35 (2 Pt 2): S1-93, review
available for $35, [an industry paid organ]. Butchko:
"When all the research on aspartame, including evaluations in both the
premarketing and postmarketing periods, is examined as a whole, it is
clear that aspartame is safe, and there are no unresolved questions
regarding its safety under conditions of intended use."
[They repeatedly pass on the ageless industry deceit that the methanol
in fruits and vegetables is as as biochemically available as that in
aspartame-- see the 1984 rebuttal by Monte, below.]

http://groups.yahoo.com/group/aspartameNM/message/911
RTP ties to industry criticized by CSPI: Murray: 12.9.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/935
comet assay finds DNA damage from sucralose, cyclamate, saccharin in
mice: Sasaki YF & Tsuda S Aug 2002: Murray 1.1.3 rmforall

http://groups.yahoo.com/group/aspartameNM/message/934
24 recent formaldehyde toxicity [Comet assay] reports:
Murray 12.31.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/622
Rich Murray: Gold: Koehler: Walton: Van Den Eeden: Leon:
aspartame toxicity 6.4.1 rmforall

http://groups.yahoo.com/group/aspartameNM/message/623
Rich Murray: Simmons: Gold: Schiffman: Spiers:
aspartame toxicity 6.4.1 rmforall

http://groups.yahoo.com/group/aspartameNM/message/917
HERP ranking of carcinogens (formaldehyde is very high):
www.berkeley.edu: Murray 12.14.2 rmforall

http://groups.yahoo.com/group/aspartameNM/message/870
Aspartame: Methanol and the Public Interest 1984:
Monte: Murray 9.23.2 rmforall

Dr. Woodrow C. Monte Aspartame: methanol and the public health.
Journal of Applied Nutrition 1984; 36 (1): 42-54.
(62 references) Professsor of Food Science
Director of the Food Science and Nutrition Laboratory
Arizona State University, Tempe, Arizona 85287
6411 South River Drive #61 Tempe, Arizona 85283-3337
602-965-6938 woody.monte@...
The methanol from 2 L of diet soda, 5.6 12-oz cans, 20 mg/can, is
112 mg, 10% of the aspartame. The EPA limit for water is 7.8 mg daily
for methanol (wood alcohol), a deadly cumulative poison. Many users
drink 1-2 L daily. The reported symptoms are entirely consistent
with chronic methanol toxicity. (Fresh orange juice has 34 mg/L, but,
like all juices, has 16 times more ethanol, which strongly protects
against methanol.)

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

Fermentation in the gut may cause disappearance of pectin (6) but the
production of free methanol is not guaranteed by fermentation (3). In
fact, bacteria in the colon probably reduce methanol directly to formic
acid or carbon dioxide (6) (aspartame is completely absorbed before
reaching the colon). Heating of pectins has been shown to cause
virtually no demethoxylation; even temperatures of 120 deg C produced
only traces of methanol (3). Methanol evolved during cooking of high
pectin foods (7) has been accounted for in the volatile fraction during
boiling and is quickly lost to the atmosphere (49).
Entrapment of these volatiles probably accounts for the elevation in
methanol levels of certain fruit and vegetable products
during canning (31, 33)."

Recent research [see links at end of post] supports his focus on the
methanol to formaldehyde toxic process:

"The United States Environmental Protection Agency in their Multimedia
Environmental Goals for Environmental Assessment recommends a minimum
acute toxicity concentration of methanol in drinking water at 3.9 parts
per million, with a recommended limit of consumption below 7.8 mg/day
(8). This report clearly indicates that methanol:

"is considered a cumulative poison
due to the low rate of excretion once it is absorbed.
In the body, methanol is oxidized to formaldehyde and
formic acid; both of these metabolites are toxic." (8)....

Recently the toxic role of formaldehyde (in methanol toxicity) has been
questioned (34). No skeptic can overlook the fact that, metabolically,
formaldehyde must be formed as an intermediate to formic acid
production (54).

Formaldehyde has a high reactivity which may be why it
has not been found in humans or other primates during methanol
poisioning (59)....

If formaldehyde is produced from methanol and does have a reasonable
half life within certain cells in the poisoned organism the chronic
toxicological ramifications could be grave.

Formaldehyde is a known
carcinogen (57) producing squamous-cell carcinomas by inhalation
exposure in experimental animals (22). The available epidemiological
studies do not provide adequate data for assessing the carcinogenicity
of formaldehyde in man (22, 24, 57).

However, reaction of formaldehyde
with deoxyribonucleic acid (DNA) has resulted in irreversible
denaturation that could interfere with DNA replication and result in
mutation (37)...."
************************************************************************