Results 1 to 4 of 4
12-01-2006, 10:54 PM #1Member
- Join Date
- Jun 1999
- Santa Fe, NM 87505, USA
aspartame carcinogenicity in rats, Ramazzini Foundation, F Belpoggi, M Soffritti, Annals NY Academy Sciences 2006 Sept, parts from 19 pages: Murray 2006.11.30
[ For related information and links:
Fiorella Belpoggi & Morando Soffritti of Ramazzini Foundation prove lifetime carcinogenicity of Coca-Cola, aspartame, and arsenic, Annals of the NY Academy of Sciences: Murray 2006.11.28
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
Morando Soffritti of Ramazzini Foundation rebuts EFSA AFC critique,
laleva.org: Murray 2006.05.05
European Food Safety Authority discounts Ramazzini study re many
cancers in 1800 rats fed lifetime doses of aspartame:
Calorie Control Council press release: Murray 2006.05.05 ]
NEWS AND EVENTS 01 November 2006
Results of 3 long term ERF carcinogenesis bioassays published in the Annals of the New York Academy of Sciences
Aspartame, Sodium Arsenite, Coca-Cola
The proceedings of the Collegium Ramazzini's 2005 conference "Framing the Future in Light of the Past: Living in a Chemical World" have been published in the Annals of the New York Academy of Sciences. The volume includes the results of three long term carcinogenesis bioassays conducted by the European Ramazzini Foundation:
Ann. N.Y. Acad. Sci. 1076: 559-577 (2006)
Results of Long-Term Carcinogenicity Bioassay on Sprague-Dawley Rats Exposed to Aspartame Administered in Feed
FIORELLA BELPOGGI, MORANDO SOFFRITTI, MICHELA PADOVANI, DAVIDE DEGLI ESPOSTI, MICHELINA LAURIOLA, AND FRANCO MINARDI.
Ann. N.Y. Acad. Sci. 1076: 578-591 (2006)
Results of a Long-Term Carcinogenicity Bioassay on Sprague-Dawley Rats Exposed to Sodium Arsenite Administered in Drinking Water
MORANDO SOFFRITTI, FIORELLA BELPOGGI, DAVIDE DEGLI ESPOSTI, AND LUCA LAMBERTINI.
Ann. N.Y. Acad. Sci. 1076: 736-752 (2006)
Results of Long-Term Carcinogenicity Bioassays on Coca-Cola Administered to Sprague-Dawley Rats
FIORELLA BELPOGGI, MORANDO SOFFRITTI, EVA TIBALDI, LAURA FALCIONI, LUCIANO BUA, AND FRANCESCA TRABUCCO.
Ann. N.Y. Acad. Sci. 1076: 559-577 (2006)
Results of Long-Term Carcinogenicity Bioassay on Sprague-Dawley Rats
Exposed to Aspartame Administered in Feed
DAVIDE DEGLI ESPOSTI,
MICHELINA LAURIOLA, AND
The end judges everything -- HERODOTUS (480-425 B.C.) The History
Cesare Maltoni Cancer Research Center,
European Foundation of Oncology and Environmental Sciences
'B. Ramazzini', 40010 Bentivoglio, Bologna, Italy
Aspartame (APM) is one of the most widely used artificial sweeteners in the world.
Its ever-growing use in more than 6000 products,
such as soft drinks, chewing gum, candy, desserts, etc.,
has been accompanied by rising consumer concerns regarding its safety, in particular its potential long-term carcinogenic effects.
In light of the inadequacy of the carcinogenicity bioassays performed in the 1970s and 1980s,
a long-term mega-experiment on APM was undertaken at the Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation on groups of male and female Sprague-Dawley rats (100-150/sex/group),
8 weeks old at the start of the experiment.
APM was administered in feed at concentrations
of 100,000, 50,000, 10,000, 2,000, 400, 80, or 0 ppm.
Treatment lasted until spontaneous death of the animals.
The results of the study demonstrate that APM causes:
(a) an increased incidence of malignant tumor-bearing animals,
with a positive significant trend in both sexes,
and in particular in females treated at 50,000 ppm (P 0.01)
when compared to controls;
(b) an increase in lymphomas-leukemias,
with a positive significant trend in both sexes,
and in particular in females treated at doses of
100,000 (P 0.01), 50,000 (P 0.01), 10,000 (P 0.05),
2000 (P 0.05), and 400 ppm (P 0.01);
(c) a statistically significant increased incidence,
with a positive significant trend, of transitional cell carcinomas of the renal pelvis and ureter in females
and particularly in those treated at 100,000 ppm (P 0.05); and
(d) an increased incidence of malignant schwannomas of the peripheral nerves, with a positive trend in males (P 0.05).
The results of this mega-experiment indicate that APM, in the tested experimental conditions, is a multipotential carcinogenic agent.
KEYWORDS: aspartame; carcinogenicity; long-term bioassays; rat
Address for correspondence: Morando Soffritti, M.D., Cesare Maltoni Cancer Research Center, European Ramazzini Foundation,
Castello di Bentivoglio, Via Saliceto, 3, 40010 Bentivoglio, Bologna,Italy.
Voice: +39-051-6640460; fax: +39-051-6640223.
e-mail: email@example.com; www.ramazzini.it
Funding for this research was provided entirely by the European Foundation on Oncology and Environmental Sciences 'B. Ramazzini'
Ann. N.Y. Acad. Sci. 1076: 559-577 (2006).
c 2006 New York Academy of Sciences.
The introduction of artificial sweeteners as substitutes for sucrose began during World Wars I and II, when the use of saccharin became prevalent due to its low cost and the wartime shortage of table sugar.1
In the following years,
two additional artificial sweeteners were introduced to the market:
cyclamate in the 1950s and aspartame (APM) in 1981.
Since the 1970s, the growing obesity problem in industrialized countries, due in part to fast food and soft drink consumption,
has lead to an increased demand for reduced-calorie foodstuffs.
Given the lucrative market for these so-called 'diet' or 'light' products, additional new-generation sweeteners have emerged,
including acesulfame-K, sucralose, and neotame.2
With the expansion of the artificial sweetener market,
concerns have arisen among consumers regarding the safety of these sweeteners and their possible long-term health effects.
At the center of this debate has been the question of the potential carcinogenic risks associated with artificial sweetener use.
Until now, no adequate epidemiological or experimental animal studies have been available.
Most epidemiological studies,
aimed to evaluate the relationship between artificial sweetener intake and cancer, have focused on sweetener consumption in general,
and not on single compounds.3
This limitation is attributed to the fact that most consumers use multiple artificial sweeteners, as different sweeteners are often blended together in food products.
Moreover, given the fact that wide consumption of artificial sweeteners emerged in the 1980s and 1990s,
epidemiological studies are, by definition,
limited in terms of exposure to the compounds.
Most long-term carcinogenicity bioassays
performed on rodents over the last 30 years
have not been adequately designed to assess carcinogenic risk.
The sensitivity of these studies in detecting risk has been greatly limited by the following factors:
(a) the number of animals per sex per group was usually 50 or less;
(b) the experiments were usually truncated at 104 weeks (or earlier)
from the start of the experiment, thus not allowing the tested compound to express its carcinogenic potential; and
(c) the conduct of the experiments was often inadequate
with incomplete or nonsystematic histopathological analysis
for all organs and tissues.
Because of the globalization of the industrialized diet and the ever-increasing use of artificial sweeteners among billions of people in both industrialized and developing countries,
and because of the inadequacy of experimental data to evaluate the potential carcinogenic effects of artificial sweeteners,
the European Ramazzini Foundation (ERF) began an integrated project of megaexperiments to test the carcinogenic potential of artificial sweeteners in the late 1990s.
In the framework of this project,
a long-term carcinogenicity bioassay on APM was begun in 1997,
in which the sweetener was administered in feed to 1800 Sprague-Dawley rats for the life span.
This article reports the complete results of this study.
APM, the methyl ester of the dipeptide L-a-aspartyl-L-phenylalanine,
has a molecular weight of 294.3 and the following structural formula:
Under particular conditions
(extreme pH, high temperature, lengthy storage times), APM may be contaminated by the diketopiperazine cycloaspartylphenylalanine (DKP).4
APM was accidentally discovered in the early 1960s,
in connection with a research project planned at the Searle & Co. laboratories to find an inhibitor of the gastrointestinal secretory hormone gastrin for the treatment of ulcers.5
For more than 30 years, APM has been increasingly used as a food additive due to its very strong, sweet taste,
estimated to be 200 times that of sucrose.
APM is the second most used artificial sweetener in the world,6
with an estimated consumption of more than 8000 tons per year in
the United States alone.7
The worldwide production of APM
is assumed to be over 16,000 tons per year.8
More than 6000 products contain APM, including soft drinks, chewing gum, table-top sweeteners, candy, desserts, yogurt, and some pharmaceutical products, such as vitamins and sugar-free cough drops.
APM is estimated to be consumed by over 200 million people worldwide.9
According to dietary surveys performed in the United States among APM
consumers during the period 1984-1992,
the average daily intake of APM ranges from 2 to 3 mg/kg of body weight (h.w.) in the general population. 10
These surveys also show that consumption by children and young
women range from about 2.5 to 5 mg/kg b.w./day. 10
The Acceptable Daily Intake (ADI) of APM
in the United States is 50 mg/kg b.w. and in Europe is 40 mg/kg b.w. 10
APM is metabolized in rodents, nonhuman primates, and humans
in the gastrointestinal tract into three constituents
(aspartic acid, phenylalanine, and methanol)
which are then absorbed and enter into the systemic circulation.11
After absorption, these compounds follow the same metabolic path as when
ingested through other foods:
aspartate and phenylalanine are used as amino acidic building blocks for protein synthesis or transformed, respectively, into
alanine plus oxalacetate 12
and tyrosine (and, partially, into phenylethylamine and phenylpyruvate).13
Methanol is oxidized to formaldehyde and then to formic acid.14
APM has been tested for genotoxicity in both in vivo and in vitro tests.
In vitro, an assay to measure the induction of unscheduled DNA synthesis in rat hepatocytes was reported to be negative, suggesting the absence of induced DNA damage by APM.15
APM was also evaluated in vitro in a chromosomal aberration test,
a sister chromatide exchange (SCE) test,
and in a micronuclei test on human lymphocytes.16
In the chromosomal aberration test, statistically significant increases (2.5-4.2-fold, compared to control values) in the percentage
of aberrant cells or in the number of chromosomal aberrations per cellwere observed in all doses.
No effect of APM was observed in the SCE test.
In the micronuclei test, a statistically increased incidence in cells with micronucleus was observed at the highest dose of treatment.
In vivo results of a test for the induction of chromosomal aberration in
bone marrow cells of male Swiss mice,
after the administration by gavage of a mixture
of APM (up to 350 mg/kg) and acesulfame potassium (up to 150 mg/kg), were negative.
A dose-related increase in the percentage of cells with chromosomal aberrations was noted with increasing doses of the two sweeteners; however, the increase was not statistically significant.17
In a peripheral blood micronuclei test conducted on
p53 haploinsufficient mice exposed for 9 months
to 50,000, 25,000, 12,500, 6250, 3125, or 0 ppm to APM in feed,
the results were judged to be positive in females on the basis of a significant trend test and the increased frequency of micronucleated erythrocytes observed in the 50,000 ppm group.18
Epidemiological studies to evaluate the relationship between APM intake
and the development of cancer in humans are not currently available, with the exception of one study in which an increased incidence of brain tumors in the United States between the 1970s and 1980s was linked to agents/situations of risk of environmental origin, and among them, consumption of APM.19
Four long-term experimental bioassays were performed on rodents in the
1970s and early 1980s.
Two long-term feeding carcinogenicity bioassays on
APM were performed on Sprague-Dawley rats
and one on mice by Searle & Co.,
the results of which were reviewed by the FDA
and summarized in the Federal Register of 1981. 20
To date, the details of these experiments have not been published.
A fourth experiment was performed on Wistar rats by
Japanese researchers and the results published in 1981,
without exhaustive experimental details.21,22
The results of these four experiments did not show
any carcinogenic effects of APM in the tested experimental conditions.
The study design, conduct, and results of these experiments were discussed by the ERF in a previous article.23
In 2005, a carcinogenicity study on APM was performed by the U.S. National Toxicology Program on genetically altered strains of mice, namely p53 haploinsufficient, Tg AC hemizygous, and Cdkn2a deficient male and female mice which develop, with increased susceptibility and decreased latency, lymphomas or sarcomas, squamous cell papillomas/carcinomas of the forestomach and brain tumors, respectively.18
Feed containing 50,000, 25,000, 12,500, 6250, 3125, or 0 ppm
was administered for 40 weeks
to groups of 15 males and 15 females.
Although the Technical Report states that in the tested experimental
conditions, no evidence of carcinogenic effects was observed,
the conclusions of the study also include the following qualification: 'because this is a new model, there is uncertainty whether the study possessed sufficient sensitivity to detect a carcinogenic effect.' 18
In light of the inadequacies and uncertainties surrounding the available epidemiological and long-term experimental data on APM,
the Cesare Maltoni Cancer Research Center (CMCRC)/ERF decided to perform a life-span megaexperiment which would evaluate the carcinogenic potential of APM when administered in feed to Sprague-Dawley rats.
MATERIALS AND METHODS
The APM used as a food grade material was produced by Nutrasweet and
supplied by Giusto Faravelli S.p.A. in Milan, Italy.
Its purity was less than 98%.
The impurities included DKP less than 1.5% and L-phenylalanine less than 0.5%.
The method used to determine its purity was an infrared absorption spectrophotometer assay.
APM was added to the standard Corticella pellet diet, used for 30 years
at the CMCRC/ERF Laboratory, at concentrations
of 100,000, 50,000, 10,000, 2000, 400, 80, or 0 ppm,
to simulate an assumed daily intake by humans
of 5000, 2500, 500, 100, 20, 4, or 0 mg/kg b.w.
The APM daily consumption in mg/kg b.w. for both males and females was calculated considering the average weight of a rat as 400 g for the duration of the experiment
and the average consumption of feed as 20 g per day.
APM was administered in feed ad libitum to Sprague-Dawley rats (100-150/sex/group), 8 weeks old at the start of the experiment.
The treatment lasted until natural death.
Control animals received the same feed without APM.
Upon death, all animals underwent complete necropsy.
The general protocols of the experiment,
including methods of tumor reporting and
statistical analysis, were described in detail in previous publications.23,24
The experiment was conducted according to the Italian law regulating the use of animals for scientific purposes.25
The study proceeded smoothly without unexpected occurrences.
The biophase ended at 151 weeks, with the death of the last animal at the age of 159 weeks.
Results of the study are reported in previous publications.23,24
Water consumption did not differ
among males and females of treated and control groups.
A dose-related difference in food consumption was observed
in both sexes during the experiment.
A slight decrease in body weight was observed
in females treated at the highest dose;
no substantial differences were observed among treated males,
compared to controls.
No differences were observed in survival among males or females of the treated groups, compared to controls.
TABLE 1. [ All cancers listed on 6 pages ]
The occurrence of benign and malignant tumors among male and female
rats is shown in Table 1.
TABLE 2. MALIGNANT TUMORS
The differences observed among treated and control
animals were as follows:
1. an increase in malignant tumor-bearing animals with a significant positive trend in males (P 0.05) and in females (P 0.01) and a statistically significant difference
in females treated at 50,000 ppm (P 0.01), compared to controls
TABLE 3. PRENEOPLASTIC AND NEOPLASTIC LESIONS OF OLFACTORY EPITHELIUM
2. an increased incidence of hyperplasia of the olfactory epithelium with a significant positive trend in males and females (Table 3).
It is noteworthy that among females treated at the highest dose,
one case of dysplastic hyperplasia,
and one olfactory neuroblastoma were observed.
The neuroblastoma invaded the cranium, compressing the forebrain and
was positive for chromogranin A immunohistochemical staining;
Table 4. PRENEOPLASTIC AND NEOPLASTIC LESIONS OF THE TRANSITIONAL CELL EPITHELIUM OF THE RENAL PELVIS AND URETER
3. an increase in the incidence of dysplastic hyperplasias, dysplastic papillomas, and carcinomas of the renal pelvis and ureter were observed in females (Table 4).
Carcinomas in females occurred with a positive trend (P 0.05) and specifically in females exposed at 100,0000 ppm (P 0.05),
compared with controls.
Carcinomas were also observed among males treated
at 100,000, 50,000, 10,000, and 2000 ppm.
In females,when dysplastic lesions and carcinomas are combined,
they show a significant positive trend (P 0.01)
and a statistically significant increase in those treated
at 100,000 (P 0.01), 50,000 (P 0.01), 10,000 (P 0.01),
2000 (P 0.05), and 400 ppm (P 0.05).
An increased incidence of deposits of calcium (mineralization) was observed in females,
particularly in those treated at 100,000 ppm (39%), 50,000 ppm (25%), or 10,000 ppm (19%), compared with controls (8%).
The same effect was not observed among males of the various groups.
No difference was observed in the incidence of acute and chronic nephropathies among males and females of all groups.
It must be noted that the nephropathy is common in the
natural dying process and for this reason,
is more frequently observed when animals are allowed to die spontaneously;
TABLE 5. MALIGNANT SCHWANNOMAS OF PERIPHERAL NERVES
4. a dose-related increased incidence in malignant schwannomas of peripheral nerves was observed,
with a significant positive trend in males (P 0.05),
while in females, nine malignancies were observed among treated
animals of the different dosage groups and none among controls
All lesions, in males and females, diagnosed as malignant schwannoma,
were positive for S100 immunohistochemical staining.
The occurrence of malignant schwannomas
mostly involved cranial nerves (72%).
The other cases arose from spinal nerve roots.
Among three males treated at the highest dose, metastases were observed in the submandibular lymph nodes in two cases,
and in the lung and liver in the third case;
TABLE 6. HEMOLYMPHORETICULAR NEOPLASIAS
5. a dose-related increased incidence in lymphomasâleukemias was observed, with a significant positive trend
in males (P 0.05) and in females (P 0.01).
When compared to controls, a statistically significant
difference was observed in females treated at doses of
100,000 (P 0.01), 50,000 (P 0.01), 10,000 (P 0.05),
2000 (P 0.05), and 400 (P 0.01) ppm (Table 6).
Lymphomas-leukemias are neoplasias
arising from hemolymphoreticular tissues and their aggregation is widely
used in experimental carcinogenesis.
The reason is that both solid and circulating phases are present
in many lymphoid neoplasms,
and the distinction between them is artificial.26
Concerning the incidence of brain malignant tumors,
a controversial issue in the experiments performed
in the 1970s and early 1980s,
12 malignant tumors (10 gliomas, 1 medulloblastoma, and 1 meningioma) were observed in our study, without dose relationship,
in males and females treated with APM,
while none were observed in controls.
In our experimental conditions,
APM causes an increased incidence of malignant tumor-bearing animals, with a positive significant trend in both sexes
and a significant increase in the incidence of tumors at various sites, including carcinomas of the renal pelvis and ureter in females, malignant schwannomas of the peripheral nerves in males, and lymphomas-leukemias in females.
The carcinogenic effects were shown
even at a daily dose of 20 mg/kg b.w.,
about half the current ADI for humans in Europe and the United States.
The results of our study are not consistent with the data made available by the producers of APM.
The interpretation of our results and the explanation for this
difference have been extensively discussed in our previous publications.23,24
The distinctive characteristics of the CMCRC/ERF long-term carcinogenicity bioassays, that is, that they are planned using a large number of animals per sex and per group
and that animals are observed until spontaneous death
have been, in our opinion, critical.
Had we truncated the experiment after just 2 years,
we would have most likely not revealed
the carcinogenic evidence of APM.
The results of our study demonstrate the necessity of an extensive review of the regulations governing the use of APM as a food additive.
The data also call for additional long-term bioassays on another species and a different calendar of exposure to better quantify
APM's carcinogenic risk.
In our opinion, it is of vital importance to also re-analyze the adequacy of the long-term carcinogenicity bioassays performed on other old- and new-generation artificial sweeteners currently in use worldwide.
Given the ever-increasing use of artificial sweeteners in both industrialized and developing countries,
we consider our integrated project on artificial sweeteners
to be of the highest priority for the protection of public health,
in particular the health of children and pregnant women
who are among the most vulnerable populations.
In light of this goal, and given what in our view are inadequate data
to date on the carcinogenicity of artificial sweeteners,
we are conducting additional research, not only on APM,
but also on other widely diffused artificial sweeteners and blends used in thousands of foods, beverages, and pharmaceutical products.
We thank the U.S. National Toxicology Program for convening a group of
pathologists to provide a second opinion for a set of malignant lesions and for their help in the statistical analysis.
We also thank the research staff of the CMCRC/ERF and Kathryn Knowles for her support in the preparation of the manuscripts.
1. BRIGHT, G. 1999.
Low-calorie sweeteners -- from molecules to mass markets.
World Rev. Nutr. Diet. 85: 3-9.
2. LINDLEY, M.G. 1999.
New developments in low-calorie sweeteners.
World Rev. Nutr. Diet. 85: 44-51.
3. WEIHRAUCH, M.R. & V. DIEHL. 2004.
Artificial sweeteners -- do they bear a carcinogenic risk?
Ann. Oncol. 15: 1460-1465.
4. BUTCHKO, H.H. et al. 2002.
Preclinical safety evaluation of aspartame.
Regul. Toxicol. Pharmacol. 35: S7-S12.
5. MAZUR, R.H. 1984.
Discovery of aspartame.
In Aspartame Physiology and Biochemistry.
L.D. Stegink & L.J. Filer, Jr. Eds.: 3-9. Dekker. New York, NY.
6. FRY, J. 1999.
The world market for intense sweeteners.
World Rev. Nutr. Diet. 85: 201-211.
7. U.S. NATIONAL LIBRARY OF MEDICINE. 2006.
Hazardous Substances Data Bank.
toxnet.nlm.nih.gov/ [accessed 10 May 2005].
8. USA FOOD NAVIGATOR.
[accessed 10 May 2005].
9. ASPARTAME INFORMATION CENTER. 2006.
aspartame.org. [accessed 10 May 2005].
10. BUTCHKO, H.H. et al. 2002.
Intake of aspartame vs the acceptable daily intake.
Regul. Toxicol. Pharmacol. 35: S13-S16.
11. RANNEY, R.E. et al. 1976.
Comparative metabolism of aspartame in experimental animals and humans.
J. Toxicol. Environ. Health 2: 441-451.
12. STEGINK, L.D. 1984.
Aspartate and glutamate metabolism.
In Aspartame Physiology and Biochemistry.
L.D. Stegink & L.J. Filer. Jr., Eds.: 47-76. Dekker. New York, NY.
13. HARPER, A.E. 1984.
In Aspartame Physiology and Biochemistry.
L.D. Stegink & L.J. Filer. Jr., Eds.: 77-109. Dekker. New York, NY.
14. OPPERMAN, J.A. 1984.
Aspartame metabolism in animals.
In Aspartame Physiology and Biochemistry.
L.D. Stegink & L.J. Filer. Jr., Eds.: 141-159. Dekker. New York, NY.
15. JEFFREY, A.M. & G.M. WILLIAMS. 2000.
Lack of DNA-damaging activity of five non-nutritive sweeteners in the rat hepatocyte/DNA repair assay.
Food Chem. Toxicol. 38: 335-338.
16. RENCUZOGULLARI, E. et al. 2004.
Genotoxicity of aspartame.
Drug Chem. Toxicol. 27: 257-268.
17. MUKHOPADHYAY, M., A.MUKHERJEE&J. CHAKRABARTI. 2000.
In vivo cytogenetic studies on blends of aspartame and acesulfame-K. Food Chem. Toxicol. 38: 75-77.
18. NATIONAL TOXICOLOGY PROGRAM. 2005.
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 on aspartame in genetically modified B6.129-Trp53tm1Brd(N5) haploinsufficient mice (feed studies). Genetically Modified Model Report NTP GMM1: 5-66.
19. OLNEY, J.W. et al. 1996.
Increasing brain tumor rates: is there a link to aspartame?
J. Neuropathol. Exp. Neurol. 55:1115-1123.
20. U.S. FOOD AND DRUG ADMINISTRATION. 1981.
Aspartame: Commissioner's final decision.
Fed. Regist. 46: 38285-38308.
21. ISHII, H. 1981.
Incidence of brain tumors in rats fed aspartame.
Toxicol. Lett. 7: 433-437.
22. ISHII, H. et al. 1981.
Toxicity of aspartame and its diketopiperazine for Wistar rats
by dietary administration for 104 weeks.
Toxicology 21: 91-94.
23. SOFFRITTI, M. et al. 2006.
First experimental demonstration of the multipotential
carcinogenic effects of aspartame administered in the feed to Sprague-Dawley rats.
Environ. Health Perspect. 114: 379-385.
24. SOFFRITTI, M. et al. 2005.
Aspartame induces lymphomas and leukaemias in rats.
Eur. J. Oncol. 10: 107-116.
25. 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.
Supplemento ordinario alla Gazzetta Ufficiale 40: 5-25.
26. HARRIS, N.L. et al. 2001.
WHO Classification of tumors of haematopoietic and lymphoid tissues: introduction.
In Tumors of Haematopoietic and Lymphoid Tissues.
E.S. Jaffe, et al., Eds.: 12-13. IARC Press. Lyon.
short aspartame (methanol, formaldehyde) toxicity research summary: Murray 2006.11.30
"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 firstname.lastname@example.org
505-501-2298 1943 Otowi Road Santa Fe, New Mexico 87505
group with 79 members, 1,385 posts in a public, searchable archive
aspartame groups and books: updated research review of 2004.07.16:
11 members of New Mexico legislature sign letter to ban aspartame as a
source of toxic methanol and formaldehyde, Stephen Fox, NM Senator
Gerald Ortiz y Pino: Murray 2006.10.22
47 UK Members of Parliament now support aspartame ban initiative of
Roger Williams, MP: Murray 2006.10.16
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
50% UK baby food is now organic -- aspartame or MSG
with food dyes harm nerve cells, CV Howard 3 year study
funded by Lizzy Vann, CEO, Organix Brands,
Children's Food Advisory Service: Murray 2006.01.13
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:
toxicity in rat brains from aspartame, Vences-Mejia A, Espinosa-Aguirre
JJ et al 2006 Aug: Murray 2006.09.06
aspartame rat brain toxicity re cytochrome P450 enzymes, expecially
CYP2E1, Vences-Mejia A, Espinosa-Aguirre JJ et al, 2006 Aug,
Hum Exp Toxicol: relevant abstracts re formaldehyde from methanol
in alcohol drinks: Murray 2006.09.29
Bristol, Connecticut, schools join state program to limit artificial
sweeteners, sugar, fats for 8800 students, Johnny J Burnham, The
Bristol Press: Murray 2006.09.22
Connecticut bans artificial sweeteners in schools, Nancy Barnes,
New Milford Times: Murray 2006.05.25
carcinogenic effect of inhaled formaldehyde, Federal Institute of Risk
Assessment, Germany -- same safe level as for Canada:
Home sickness -- indoor air often worse, as our homes seal in
[one is formaldehyde, also from the 11% methanol part of aspartame],
Megan Gillis, WinnipegSun.com: Murray 2006.06.01
methanol (formaldehyde, formic acid) disposition: Bouchard M
et al, full plain text, 2001: substantial sources are
degradation of fruit pectins, liquors, aspartame, smoke:
NIH NLM ToxNet HSDB Hazardous Substances Data Bank
inadequate re aspartame (methanol, formaldehyde, formic acid):
HSDB Hazardous Substances Data Bank: Aspartame
ASPARTAME CASRN: 22839-47-0
METHANOL CASRN: 67-56-1
FORMALDEHYDE CASRN: 50-00-0
FORMIC ACID CASRN: 64-18-6
formaldehyde from 11% methanol part of aspartame or from red wine
causes same toxicity (hangover) harm: Murray 2006.05.24
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.
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
Aspartame Toxicity Information Center Mark D. Gold
12 East Side Drive #2-18 Concord, NH 03301 603-225-2100
"Scientific Abuse in Aspartame Research"
Russell L. Blaylock, MD discusses MSG, aspartame, excitotoxins
with Mike Adams: Murray 2006.09.27
Mike Adams interviews Randall Fitzgerald on "The Hundred Year Lie:
How Food and Medicine are Destroying Your Health" 2006.06.21:
************************************************** *****Send blank post to: <br />aspartameNMemail@example.com to join<br />free,open, list with searchable archives for toxicity issues.<br />Richard \"Rich\" T. Murray Room For All 1943 Otowi Road Santa Fe, NM 87505<br />firstname.lastname@example.org 505-501-2298
12-01-2006, 11:29 PM #2
IMO....If a soda pop drinker desires to not get fat and aspartame will aid in staying thin, the choice is up to the soda pop drinker.
Gee who cares about science. There are studies on both side of the issue.
Who the F cares...my being obese will kill me sooner than drinking 4 cans of diet pepsi every day.
[ 12-01-2006, 11:32 PM: Message edited by: Mr Zabe ]Don't worry, be happy. Meher Baba
01-03-2007, 03:12 AM #3Senior Member
- Join Date
- Apr 2005
funny thing is i know people who have been drinking tab since it was introduced and are perfectly healthy.... same with diet coke...
01-03-2007, 12:53 PM #4Member
- Join Date
- Jun 1999
- Santa Fe, NM 87505, USA
That's right, sirslash, there are big, complex variations among people -- genetic, diet, disease, toxicity exposures, exercise, age, drugs, medicines -- and very little research about how many people are vulnerable to long-term heavy use of the various artificial sweeteners.
Rich MurraySend blank post to: <br />aspartameNMemail@example.com to join<br />free,open, list with searchable archives for toxicity issues.<br />Richard \"Rich\" T. Murray Room For All 1943 Otowi Road Santa Fe, NM 87505<br />firstname.lastname@example.org 505-501-2298