Lifetime exposure to low doses of aspartame beginning during prenatal
life increases cancer effects in rats, Morando Soffritti et al,
European Ramazzini Foundation, USA EPA Environmental Health
Perspectives 2007.06.13 free full text 24 pages: Murray 2007.06.16
http://groups.yahoo.com/group/aspartameNM/message/1441 www.ehponline.org/members/2007/10271/10271.pdf free full text 24
pages
" CONCLUSIONS
The results of our second long-term carcinogenicity bioassay on APM
not only confirm, but also reinforce our first experimental
demonstration of APM's multipotental carcinogenicity at a dose level
close to the human ADI.
Furthermore, the study demonstrates that when lifespan exposure to APM
begins during fetal life, its carcinogenic effects are increased.
On the basis of the present findings, we believe that a review of the
current regulations governing the use of aspartame cannot be delayed.
This review is particularly urgent with regard to aspartame-containing
beverages, heavily consumed by children. "
" APM is metabolized in the gastric tract of rodents, non-human
primates and humans to its three constituents: aspartic acid,
phenylalanine and methanol.
When absorbed, aspartic acid is transformed into alanine plus
oxaloacetate (Stegink 1984);
phenylalanine is transformed mainly into tyrosine and, to a lesser
extent, phenylethylamine and phenylpyruvate (Harper 1984);
and methanol is transformed into formaldehyde and then to formic acid
(Opperman 1984). "
www.ramazzini.it/fondazione/newsDetail.asp?id=17
news archive|archivio notizie
overview/sommario
June 14, 2007
Second Ramazzini aspartame study in press in Environmental Health
Perspectives
A second ERF study on the artificial sweetener aspartame, entitled
"Lifespan Exposure to Low Doses of Aspartame Beginning During Prenatal
Life Increases Cancer Effects in Rats"
has been accepted for publication in Environmental Health
Perspectives.
page [Vedi testo completo per l'italiano]
The full text of the article is available online at:
http://www.ehponline.org/docs/2007/10271/abstract.html
Environmental Health Perspectives (EHP), the peer-reviewed journal of
the United States' National Institute of Environmental Health
Sciences, is an important vehicle for the dissemination of
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Study Abstract
Background.
In a previous study conducted at the Cesare Maltoni Cancer Research
Center of the European Ramazzini Foundation (CMCRC/ERF), we
demonstrated for the first time that aspartame (APM), administered
with feed at various doses to 8 week-old Sprague Dawley rats for the
lifespan, is a multipotent carcinogenic agent.
Objective.
The aim of this second study is to better quantify the carcinogenic
risk of APM, beginning treatment during fetal life.
Methods.
The study was conducted on groups of 70-95 male and female Sprague
Dawley rats, administered APM with feed at concentrations of 2000,
400, or 0 ppm from the 12th day of fetal life until natural death.
Results.
The results of the study show:
a) a significant dose-related increase of malignant tumor-bearing
animals in males (p<0.01),
in particular in the group treated at 2000 ppm (p 0.01);
b) a significant increase of the incidence in lymphomas/leukemias in
males treated at 2000 ppm (p 0.05)
and a significant dose-related increase of the incidence of lymphomas/
leukemias in females (p 0.01),
in particular in the group treated at 2000 ppm (p 0.01);
c) a significant dose-related increase of the incidence of mammary
cancer in females (p 0.05),
in particular in the group treated at 2000 ppm (p 0.05).
Conclusions.
The results of this carcinogenicity bioassay not only confirm, but
also reinforce the first experimental demonstration of APM's
multipotential carcinogenicity at a dose level close to the acceptable
daily intake (ADI) for humans.
Furthermore, the study demonstrates that when lifespan exposure to APM
begins during fetal life, its carcinogenic effects are increased.
Link to first Ramazzini APM study (Environ Health Perspect 114:
379-385, 2006):
First Experimental Demonstration of the Multipotential Carcinogenic
Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats
Press contact: Kathryn Knowles
development@ramazzini.it
IT: Il secondo studio Ramazzini sull'aspartame in stampa sul giornale
scientifico Environmental Health Perspectives
Un secondo studio sul dolcificante artificiale aspartame, della
Fondazione Europea Ramazzini, dal titolo "L'Esposizione ad Aspartame a
Basse Dosi, dalla Vita Fetale e per Tutta la Vita, Aumenta gli Effetti
Cancerogeni sui Ratti", è stato accettato per essere pubblicato su
Environmental Health Perspectives.
Il testo completo dell'articolo è disponibile online:
http://www.ehponline.org/docs/2007/10271/abstract.html
Environmental Health Perspectives (EHP), il giornale peer-reviewed
dell'Istituto Nazionale di Scienze Ambientali Americano, è un
importante veicolo per la divulgazione di informazioni riguardanti
ambiente, salute pubblica e risultati scientifici. La finalità di EHP
è essere un forum utile al dibattito sull'interrelazione tra ambiente
e salute pubblica, divulgando, in maniera equilibrata e obiettiva, le
ricerche peer-reviewed maggiormente significative e le notizie più
attuali e credibili del settore. Con un fattore di impatto del 5,34,
EHP appare tra i primi su 132 giornali di scienze ambientali e primo
tra 90 giornali di salute pubblica, ambientale e occupazionale. EHP
viene letto in oltre 190 paesi.
Riassunto dello studio
Premesse. In un precedente studio condotto al Centro di Ricerca sul
Cancro Cesare Maltoni della Fondazione Europea Ramazzini (CRCCM/FER),
è stato dimostrato per la prima volta che l'aspartame (APM),
somministrato con il cibo a varie dosi, a ratti Sprague-Dawley di 8
settimane di età fino alla morte spontanea, è un agente cancerogeno
multipotente. Finalità. L'obiettivo di questo secondo studio è di
meglio quantificare il rischio cancerogeno dell'APM, iniziando il
trattamento durante la vita fetale. Metodi. Lo studio è stato condotto
su gruppi di 70-95 ratti Sprague-Dawley maschi e femmine, a cui
l'aspartame è stato somministrato col cibo a concentrazioni di 2000,
400, o 0 ppm dal dodicesimo giorno della vita fetale fino alla morte
naturale. Risultati. I risultati dello studio dimostrano: a) un
aumento significativo, dose correlato, di animali portatori di tumori
maligni nei maschi (p 0.01), in particolare nel gruppo trattato a 2000
ppm (p 0.01); b) un aumento significativo dell'inci
denza di linfomi/leucemie nei maschi trattati a 2000 ppm (p 0.05) e un
aumento significativo, dose correlato, nell'incidenza di linfomi/
leucemie nelle femmine (p<0.01), in particolare nel gruppo trattato a
2000 ppm (p 0.01); c) un aumento significativo, dose correlato,
nell'incidenza di cancro mammario nelle femmine (p 0.05), in
particolare nel gruppo trattato a 2000 ppm (p 0.05). Conclusioni. I
risultati di questo saggio di cancerogenicità non solo confermano, ma
rinforzano la prima dimostrazione sperimentale della cancerogenicità
multipotente dell'APM a un livello di dose vicino a quello
giornalmente ammesso per gli esseri umani. Inoltre, lo studio dimostra
che quando l'esposizione all'APM inizia durante la vita fetale, gli
effetti cancerogeni aumentano.
Link al primo studio sull'aspartame della Fondazione Europea Ramazzini
(Environ Health Perspect 114:379-385, 2006): "Prima Dimostrazione
Sperimentale degli Effetti Cancerogeni Multipotenti dell'Aspartame
Somministrato nel Cibo a Ratti Sprague-Dawley".
Contatto stampa: Kathryn Knowles
development@ramazzini.it
This EHP-in-Press article has been peer-reviewed, revised, and
accepted for publication.
The EHP-in-Press articles are completely citable using the assigned
DOI code for the article.
This document will be replaced with the copyedited and formatted
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Through the DOI number used in the citation, you will be able to
access this document at each stage of the publication process.
Environ Health Perspect doi:10.1289/ehp.10271 available via
http://dx.doi.org/
[Online 13 June 2007]
The full version of this article is available for free in PDF format.
www.ehponline.org/docs/2007/10271/abstract.html www.ehponline.org/members/2007/10271/10271.pdf free full text 24
pages
National Institutes of Health
U.S. Department of Health and Human Services
ENVIRONMENTAL HEALTH PERSPECTIVES
ehponline.org
Lifespan Exposure to Low Doses of Aspartame Beginning During Prenatal
Life Increases Cancer Effects in Rats
doi:10.1289/ehp.10271 (available at
http://dx.doi.org/)
Online 13 June 2007
Morando Soffritti 1,
Fiorella Belpoggi 1,
Eva Tibaldi 1,
Davide Degli Esposti 1,
Michela Lauriola 1
1 Cesare Maltoni Cancer Research Center, European Ramazzini Foundation
of Oncology and Environmental Sciences, Bologna Italy
Address of the institution: Cesare Maltoni Cancer Research Center,
European Ramazzini Foundation of Oncology and Environmental Sciences
Castello di Bentivoglio, Via Saliceto, 3, 40010 Bentivoglio, Bologna,
Italy
Tel: +39 051 6640460 Fax: +39 051 6640223
e-mail:
crcfr@ramazzini.it www.ramazzini.it
Address correspondence to: M. Soffritti
page 2
Acknowledgements:
This research was supported entirely by the European Ramazzini
Foundation
of Oncology and Environmental Sciences.
The authors declare that they have no competing financial interests.
Short running head: Carcinogenicity of Aspartame
Key words: artificial sweeteners, aspartame, carcinogenicity,
lymphomas/leukemias, mammary cancers, prenatal exposure, Sprague-
Dawley
Abbreviations:
ADI acceptable daily intake
APM aspartame
BW body weight
CMCRC Cesare Maltoni Cancer Research Center
EFSA European Food Safety Authority
ERF European Ramazzini Foundation
EU European Union
FDA Food and Drug Administration
page 3
Outline of section headers
Abstract
Introduction
Materials and Methods
Results
Discussion
Conclusions
References
Tables
Figure legends
Figures
Total paper word count: 4,960
page 4
ABSTRACT
page 5
INTRODUCTION
Aspartame (APM) is one of the most widely used artificial sweeteners
in the world.
First approved by the US Food and Drug Administration (FDA) for
limited use in solid food in 1981, its
authorization was extended to soft drinks in 1983 and then approved as
a general sweetener in 1996
(FDA 1981; FDA 1983; FDA 1996).
Likewise, the sweetener was approved for general use in the European
Union (EU) in 1994 (EC Directive 1994).
Today APM is present in over 6000 consumer packaged goods and in
nearly 500 pharmaceutical products, including children's medicines
(Aspartame Information Center 2005).
In the United States, over 70% of aspartame sales are attributed to
soft-drinks (American Dietetic Association 2004).
The acceptable daily intake (ADI) of aspartame is currently 50 mg/kg
body weight (bw) in the USA and 40 mg/kg bw in the EU for both
children and adults.
Daily assumption of artificial sweeteners by women of childbearing age
and children has been estimated between 2.5 - 5.0 mg/kg bw (Butchko et
al. 2002).
In a study of Swedish diabetics, although the general APM intake was
lower than the ADI, the worst-case calculation of intake in the
children's group was reported to be 114% of ADI (Ilbäck et al 2003).
APM is metabolized in the gastric tract of rodents, non-human primates
and humans to its three constituents: aspartic acid, phenylalanine and
methanol.
When absorbed, aspartic acid is transformed into alanine plus
oxaloacetate (Stegink 1984);
phenylalanine is transformed mainly into tyrosine and, to a lesser
extent, phenylethylamine and phenylpyruvate (Harper 1984);
and methanol is transformed into formaldehyde and then to formic acid
(Opperman 1984).
In vitro and in vivo tests demonstrate that APM is not genotoxic.
Likewise, long term carcinogenicity studies conducted by the
manufacturers of aspartame using rats and mice in the '70s and '80s
did not demonstrate any carcinogenic effects.
We have reported a detailed review of the genotoxicity and
carcinogenicity studies available to date on APM in previous
publications. (Belpoggi et al. 2006; Soffritti et al. 2005; Soffritti
et al. 2006).
In our opinion, the small number of animals used per sex/per group and
the termination of these experiments after 110 weeks of age rather
than observing animals for the lifespan, represent limiting factors
when evaluating the
page 6
carcinogenic risk or safety of artificial sweeteners such as
aspartame.
It was for this reason, together with the growing use of APM in
industrialized countries, that we designed and performed a mega-
experiment using 7 groups of Sprague-Dawley rats (100-150/sex/group),
treated with APM in feed at various dose levels (including one very
close to the ADI for humans), from 8 weeks of age until natural death.
The study demonstrated for the first time that APM is a multipotential
carcinogenic agent, capable of inducing, in our experimental
conditions:
a) a significant, doserelated increased incidence of malignant tumor-
bearing animals in males (p 0.05) and in females (p 0.01), in
particular in females treated at 50,000 ppm (p 0.01);
b) a significant dose-related increase in lymphomas/leukaemias in both
males (p 0.05) and females (p 0.01), in particular in females treated
at doses of 100,000 (p 0.01), 50,000 (p 0.01), 10,000 (p 0.05), 2,000
(p 0.05), or 400 ppm (p 0.01);
c) a significant, dose-related increased incidence (p 0.01), of
transitional cell carcinomas of the renal pelvis and ureter and their
precursors (dysplasias) in females treated at
100,000 (p 0.01), 50,000 (p 0.01), 10,000 (p 0.01), 2,000 (p 0.05), or
400 ppm (p 0.05);
d) a significant, dose-related increased incidence of malignant
schwannomas of peripheral nerves (p 0.05) in males (Belpoggi et al.
2006; Soffritti et al. 2005; Soffritti et al. 2006).
Given the consolidated experience of the European Ramazzini Foundation
(ERF) in the conduct of long term bioassays, and the large number of
rodents used in the study, the results attracted the attention of the
scientific community, consumer and industry associations, and the
national and international agencies responsible for food safety,
including the Italian Superior Council of Health, the European Food
Safety Authority (EFSA), the US FDA, Health Canada, and others.
Per their request, each of these agencies was provided with all
available raw data related to the study.
To our knowledge, only EFSA has issued an official opinion on our
study, releasing on May 5, 2006 a 40-page report in which they
concluded that it is not necessary to revise their previous
opinion on the absolute safety of APM (EFSA 2006).
Subsequent to our findings of hematopoietic cancers in rats, and in
light of persistent concerns among the scientific community of an
association between APM and brain cancers, Lim et al (2006)
page 7
published the results of a study which assessed the correlation
between the consumption of aspartame-containing beverages and the
incidence of these types of cancers.
The findings were based on data derived from a prospective study
conducted by the US National Institutes of Health and the American
Association of Retired Persons, using a cohort of over 285,000 men and
over 188,000 women between the ages of 50-71, who had satisfactorily
responded to a self-administered food frequency questionnaire.
Among the survey questions was the consumption of beverages (soda,
fruit drinks, sweetened iced tea) potentially containing APM during
the previous year.
The questionnaires were mailed from 1995 to 1996 and the follow-up
lasted until 2000.
The conclusions of the study did not support the hypothesis that APM
increases hematopoietic or brain cancer risks.
Recently a group of Italian authors (Gallus et al. 2007) published the
results of an integrated network of case-control studies conducted in
Italy between 1991-2004 on the potential correlation between
artificial sweeteners (including APM) and cancer.
The authors interviewed patients with histologically confirmed cancers
of the oral cavity and pharynx (598), esophagus (304), colon (1225),
rectum (728), larynx (460), breast (2569), ovary (1031), prostate
(1294) and kidney (renal cell carcinoma 767).
Controls were 7028 patients (3301 men and 3727 women) admitted to the
same hospitals for acute, non-neoplastic disorders.
Cases and controls were interviewed during their hospital stay, using
a questionnaire on subjects' usual diet in the 2 years before
diagnosis.
The results reported a lack of association between artificial
sweeteners and the risk of the aforementioned cancers.
As soon as we perceived the carcinogenic effects of APM during the
elaboration of the data in our first mega-experiment, we planned an
integrated program of long-term bioassays, beginning treatment from
prenatal life, on a total of more than 4000 rats and mice in order to
better quantify the carcinogenic risks of aspartame.
In this report we present the results of a second study on APM in
which male and female Sprague-Dawley rats were exposed to very low
doses of APM in feed (100 or 20 mg/kg bw) from fetal life until
natural death.
page 8
MATERIALS AND METHODS
The APM used was produced by Ajinomoto and supplied by Giusto
Faravelli S.p.A. in Milan, Italy.
Its purity, as determined by an infrared absorption spectrophotometer
assay, was over 98.7%:
diketopiperazine was under 0.3% and L-phenylalanine was under 0.5%.
APM was added to the standard diet, used from more than 30 years at
the Cesare Maltoni Cancer Research Center (CMCRC)/ERF,
at concentrations of 2000; 400; or 0 ppm in order to simulate an
assumed daily APM intake of 100; 20; or 0 mg/kg bw.
The feed was supplied by the producer on monthly basis.
The stability of the aspartame in feed was analyzed prior to the start
of the study and periodically confirmed throughout the course of the
biophase.
The daily APM assumption in mg/kg bw was calculated considering the
average body weight both for males and females as 400 g for the
duration of the experiment and the daily consumption of feed as 20 g/
day.
The feed was supplied ad libitum to groups of 70-95 male and female
Sprague-Dawley rats from the colony of the CMCRC/ERF.
The basic tumorigram of this strain of rats is well known and the
susceptibility to cancer does not differ greatly from that of humans.
Treatment began during fetal life, administering APM in feed to female
breeders from the 12th day of pregnancy, when organogenesis is
completed and before which time many tissues and organs are refractory
to the effects of carcinogenic agents (IARC 1973).
The breeders were sacrificed after weaning and treatment of the
offspring lasted until natural death.
Control animals received the same feed without APM.
At 4-5 weeks of age, after weaning, the experimental animals were
identified by ear punch, separated by sex and assigned to a respective
dose group, depending on the APM concentration
administered to the breeder.
They were then housed, in groups of 5, in makrolon cages (41x25x15
cm), with stainless-steel wire tops and a shallow layer of white wood-
shavings as bedding, and kept in a room used only for this experiment,
at a temperature of 23 plus or minus 2 deg C and relative humidity of
50-60%.
page 9
All animals were kept under observation until natural death.
The experiment was conducted according to Italian law regulating the
use and humane treatment of animals for scientific purposes (Decreto
Legislativo N. 116 1992).
Mean daily drinking water and feed consumption were measured per cage,
and body weight measured individually, beginning at 6 weeks of age and
continuing once a week for the first 13
weeks, then every two weeks until 110 weeks of age.
Measurement of body weight continued every 2 weeks until the end of
the experiment.
In order to detect and register all gross lesions, the animals were
clinically examined every 2 weeks for the duration of the experiment.
In order to evaluate the status and behavior of the animals and to
limit the post mortem modifications, a patrol was performed three
times daily from Monday to Friday and twice on Saturdays, Sundays and
holidays.
Deceased animals were registered and kept refrigerated for a maximum
of 16-19 hours at 4°C until necropsy.
The biophase ended at 147 weeks, with the death of the last animal at
the age of 144 weeks.
Upon death, all animals underwent complete necropsy. Histopathology
was routinely performed on the following organs and tissues of each
animal from each group:
skin and subcutaneous tissue, mammary gland, the brain (3 sagittal
sections), pituitary gland, Zymbal glands, salivary glands, Harderian
glands, cranium (five sections, with oral and nasal cavities and
external and internal ear ducts), tongue,
thyroid, parathyroid,
pharynx, larynx, thymus and mediastinal lymph nodes, trachea, lung and
mainstem bronchi, heart, diaphragm, liver, spleen, pancreas, kidneys,
adrenal glands, esophagus, stomach (fore and glandular), intestine
(four levels), urinary bladder, prostate, vagina, gonads,
interscapular brown fat pad, subcutaneous and mesenteric lymph nodes,
and other organs or tissues with pathological lesions.
All organs and tissues were preserved in 70% ethyl alcohol, except for
bones which were fixed in 10% formalin and then decalcified with 10%
formaldehyde and 20% formic acid in water solution.
The normal specimens were trimmed, following the CMCRC/ERF Laboratory
standard operating procedures.
The pathological tissue was trimmed to
page 10
allow for the largest surface including normal adjacent tissue.
Trimmed specimens were processed as paraffin blocks, and 3-5 micro-m
sections of every specimen were obtained.
Sections were routinely stained with hematoxylin and eosin.
All slides were examined microscopically by the same group of
pathologists, following the same criteria of histopathological
evaluation and classification.
A senior pathologist reviewed all tumors and all other lesions of
oncologic interest.
Statistical evaluations of the incidence and dose-response
relationship of neoplastic lesions were performed using the Cox
regression model (Cox 1972).
The p-values are reported in the tables.
RESULTS
The experiment proceeded smoothly without unexpected occurrences.
No relevant differences were observed in feed consumption between
treated and untreated groups, in both males and females (Figure 1A,
1B).
No differences were observed in water consumption in both males and
females in the various groups.
No difference in mean body weight was observed in the treated groups
compared to the control (Figure 1C).
A slight decrease, seemingly dose-related, in survival was observed
between the treated groups and the control group in both males and
females (Figure 1D, 1E).
Oncologic results are reported in Table 1 for males and Table 2 for
females.
Multiple tumors of different type and site, of different type in the
same site, of the same type in bilateral organs, of the same type in
the skin, in the subcutaneous tissue, in mammary glands, or at distant
sites of diffuse tissue (i.e. bones and skeletal muscle) were plotted
as single/independent tumors.
Multiple tumors of the same type in the same tissue and organ, apart
those listed above, were plotted only once.
Total malignant tumors.
The incidence of malignant tumor-bearing animals occurred with a
significant, dose-related increase in males (p 0.01).
A significant increase of the incidence of malignant tumors was
observed in males treated at 2000 ppm (p 0.01) compared to the control
group (Table 1).
Albeit not significant, a numeric increase of the incidence of animals
bearing
page 11
malignant tumors was also observed among females exposed at 2000 ppm
compared to the controls (Table 2).
Tumor types which contributed most to this increased incidence are
presented as follows:
Lymphomas/leukemias.
The occurrence of lymphomas/leukemias in males and females is reported
in Tables 1 and 2.
The data show that APM causes a significant, dose-related increased
incidence in females (p 0.01).
When compared to untreated control group, the increased incidence of
lymphomas/leukemias in treated males and females was significant at
2000 ppm (p 0.05 and p 0.01 respectively).
In males, the most frequent histotypes observed in the experiment were
lymphoimmunoblastic lymphomas, mainly involving lung and mediastinal/
peripheral nodes.
In females, the most frequent histocytotypes were lymphocitic
lymphomas and lymphoimmunoblastic lymphomas mainly involving the
thymus, lung, spleen and peripheral nodes.
The differential diagnoses were based on the morphological criteria
regularly used in our laboratories, according to the guidelines of the
International Classification of Rodent Tumors (IARC 1993).
Lymphomas/leukemias (this term includes all types of
hemolymphosarcomas and leukemias) are neoplasias arising from
hemolymphoreticular tissues, and their aggregation is regularly used
in experimental carcinogenesis.
The reason, as has been widely noted, is that both solid and
circulating phases are present in many lymphoid neoplasms, and
distinction between them is artificial (Harris et al. 2001).
Mammary Carcinomas.
The incidence of mammary gland carcinomas in males and females are
reported in Tables 1 and 2.
A dose-related increase in the incidence of carcinomas was observed in
females (p 0.05).
The incidence of lesions in females exposed at 2000 ppm was
significantly higher (p 0.05) compared to the controls.
Two carcinomas were also observed among males treated at 2000 ppm.
Historical controls.
The overall incidence of lymphomas/leukemias among male and female
Sprague-Dawley rats and mammary cancers in female Sprague-Dawley rats
in our laboratory over the last 20 years is reported in the footnotes
of the respective tables.
page 1 2
DISCUSSION
In our first mega-experiment, we demonstrated for the first time that
APM is a multipotential carcinogenic agent inducing, among other
cancers, a dose-related, significant increase in
lymphomas/leukemias in females (Belpoggi et al. 2006; Soffritti et al.
2005; Soffritti et al. 2006).
In the present experiment, in which APM was administered in feed
beginning during fetal life to Sprague-Dawley rats at doses of 2000 or
400 ppm (equivalent to an assumption of 100 and 20 mg/kg bw), we again
confirmed that APM induces carcinogenic effects, namely:
a) a significant dose-related increase of malignant tumor-bearing
animals in males (p 0.01), in particular in the group treated at 2000
ppm (p 0.01);
b) a significant increase of the incidence of lymphomas/leukemias in
males treated at 2000 ppm (p 0.05) and a significant dose-related
increase of the incidence of lymphomas/leukemias in females (p 0.01),
in particular in the group treated at 2000 ppm (p 0.01);
c) a significant dose-related increase of the incidence of mammary
cancer in females (p 0.05), in particular in the group treated at 2000
ppm (p 0.05).
When comparing lifespan exposure beginning during post- and prenatal
life, we have shown that prenatal exposure to APM clearly increases
the incidence of lymphomas/leukemias in females (Table 3).
Moreover, when comparing the cumulative prevalence by age of death of
hemolymphoreticular neoplasias, it is clear that prenatal exposure to
APM also accelerates the insurgence of these lesions in females
(Figure 2A, 2B).
With regard to males, the incidence of lymphomas/leukemias in the
concurrent control (9.5%) falls within the lower range of our
historical controls (8.0-30.9%), and the incidence of
lymphomas/leukemias in the group treated at the highest dose (17.1%)
is close to the overall historical incidence (20.9%).
Since the incidence of lymphomas/leukemias observed in males treated
at 2000 ppm is close to double the concurrent control, we consider
these effects to be related to APM exposure (Haseman et al. 1984;
Haseman 1992; Haseman 1995).
The results of our second experiment further disprove the alternative
hypothesis suggested by EFSA regarding the cause of lymphomas/
leukemias in our colony, in which they consider the
page 13
incidence of lymphomas/leukemias observed in our first experiment
"unrelated to APM given the high background incidence of chronic
inflammatory changes in the lung" (EFSA 2006).
First of all, as previously reported (Soffritti 2006), experimental
animals which are allowed to die spontaneously are subject to
infectious pathologies which are part of the natural dying process in
both rodents and humans.
Secondly, among the animals bearing lymphomas/leukemias, the diffusion
of neoplastic tissue was observed not only in the lung, but also
concurrently in various organs (liver, spleen, mediastinal and other
lymph nodes).
Finally, it should be noted that out of 49 agents reported to be
carcinogenic in rats by the CMCRC/ERF, only 8 of these agents induced
hemolymphoreticular malignancies.
Of these, 3 were demonstrated in both males and females, namely
formaldehyde (Soffritti et al 2002b), mancozeb (Belpoggi et al 2002a),
di-isopropyl-ether (Belpoggi et al 2002b), and 5 in only females,
namely toluene (Soffritti et al 2004), methyl alcohol (Soffritti et al
2002a), methyl tert-butyl ether (Belpoggi et al 1995), tert-amyl-
methyl-ether (Belpoggi et al 2002b) and APM (Belpoggi et al. 2006;
Soffritti et al. 2005; Soffritti et al. 2006).
The two aforementioned epidemiological studies published after our
first mega-experiment merit general comment.
Both studies consider the eating habits of a large population of males
and females, age 50-70, in the 1990s.
Given the timeframe of these surveys and the commercialization of
aspartame in the 1980s, the subjects' potential use of the sweetener
could not have exceeded 10-15 years.
It is difficult to think that this limited adult period of exposure to
APM could evidence or exclude a potential carcinogenic risk.
The design of these studies underlines the importance of conducting an
epidemiological study in which exposure to APM is monitored beginning
from fetal life, particularly given the use of products containing APM
by women of child-bearing age and children.
page 14
CONCLUSIONS
The results of our second long-term carcinogenicity bioassay on APM
not only confirm, but also reinforce our first experimental
demonstration of APM's multipotental carcinogenicity at a dose level
close to the human ADI.
Furthermore, the study demonstrates that when lifespan exposure to APM
begins during fetal life, its carcinogenic effects are increased.
On the basis of the present findings, we believe that a review of the
current regulations governing the use of aspartame cannot be delayed.
This review is particularly urgent with regard to aspartame-containing
beverages, heavily consumed by children.
page 15
REFERENCES
American Dietetic Association. 2004.
Position on the use of nutritive and non nutritive sweeteners.
J Am Diet Assoc 104: 225-275.
Aspartame Information Center. 2005.
Aspartame Information Center Homepage. Available:
http://www.aspartame.org [accessed 27 October 2005].
Belpoggi F, Soffritti M, Bua L, Guarino M, Lambertini L, Cevolani D,
et al. 2002a.
Results of longterm experimental studies on the carcinogenicity of
ethylene-bis-dithiocarbamate (Mancozeb) in rats.
Ann NY Acad Sci 982: 123-136.
Belpoggi F, Soffritti M, Maltoni C. 1995.
Methyl-tertiary-butyl ether (MTBE), a gasoline additive, causes
testicular and lymphohaematopoietic cancers in rats.
Toxicol Ind Health 11: 119-149.
Belpoggi F, Soffritti M, Minardi F, Bua L, Cattin E, Maltoni C. 2002b.
Results of long-term carcinogenicity bioassays on Tert-Amyl-Methyl-
Ether (TAME) and Di-Isopropyl-Ether (DIPE) in rats.
Ann NY Acad Sci 982: 70-86.
Belpoggi F, Soffritti M, Padovani M, Degli Esposti D, Lauriola M,
Minardi F. 2006.
Results of long term carcinogenicity bioassay on Sprague-Dawley rats
exposed to aspartame administered in feed.
Ann NY Acad Sci 1076: 559-577.
Butchko HH, Stargel WW, Comer CP, Mayhew DA, Benninger C, Blackburn
GL, et al. 2002.
Intake of aspartame vs. the acceptable daily intake.
Regul Toxicol Pharmacol 35: S13-S16.
Cox DR. 1972.
Regression models and life tables.
J Royal Stat Society, Series B, 34: 187-220.
Decreto Legislativo 116. 1992.
Attuazione della direttiva n. 86/609/CEE in materia di protezione
degli animali utilizzati a fini sperimentali o ad altri fini
scientifici [in Italian].
Supplemento ordinario alla Gazzetta Ufficiale 40: 5-25.
EC Directive 35. 1994.
Directive 94/35/EC of 30 June 1994 on sweeteners for use in
foodstuffs.
Official Journal L 237: 3-12.
page 16
EFSA (European Food Safety Authority). 2006.
Opinion of the Scientific Panel AFC Related to a New Long-Term
Carcinogenicity Study on Aspartame. Available:
http://www.efsa.eu.int/science/afc/a...s/1471_en.html [accessed
1 June 2006].
FDA (Food and Drug Administration). 1981.
Aspartame: commissioner's final decision.
Fed Reg 46: 38285-38308.
FDA (Food and Drug Administration). 1983.
Food additives permitted for direct addition to food for human
consumption: aspartame.
Fed Reg 48: 31376-31382.
FDA (Food and Drug Administration). 1996.
Food additives permitted for direct addition to food for human
consumption: aspartame.
Fed Reg 61: 33654-33656.
Gallus S, Scotti L, Negri E, Talamini R, Franceschi S, Montella M, et
al. 2007.
Artificial sweeteners and cancer risk in a network of case-control
studies.
Ann Oncol 18: 40-44.
Harper AE. 1984.
Phenylalanine metabolism.
In: Aspartame Physiology and Biochemistry (Stegink LD, Filer LJ Jr,
eds). New York: Dekker, 77-109.
Harris NL, Jaffe ES, Vardiman JW, Stein H, Diebold J, Müller-
Hermelink HK, et al. 2001.
WHO Classification of tumors of haematopoietic and lymphoid tissues:
introduction.
In: Tumors of Haematopoietic and Lymphoid Tissues (Jaffe ES, Harris
NL, Stein H, Vardiman JW, eds). Lyon, France: IARC Press, 12-13.
Haseman JK. 1992.
Value of historical controls in the interpretation of rodent neoplasm
data.
Drug Inf J 26:191-200.
Haseman JK. 1995.
Data Analysis: statistical analysis and use of historical control
data.
Regul Toxicol Pharmacol 21: 52-59.
Haseman JK, Huff JE, Boorman GA. 1984.
Use of historical control data in carcinogenicity studies in rodents.
Toxicol Pathol 12: 126-135.
IARC. 1973.
Transplacental Carcinogenesis.
IARC Sci Publ 4: 71-83.
IARC. 1993.
Haematopoietic system.
IARC Sci Publ 122: 1-27.
page 17
Ilbäck NG, Alzim M, Jahrl S, Henghardt-Barbieri H, Busk L. 2003.
Estimated intake of the artificial sweeteners acesulfame-K, aspartame,
cyclamate and saccharin in a group of Swedish diabetics.
Food Add Contam 20: 99-114.
Lim U, Subar AM, Mouw T, Hartge P, Morton LM, Stolzenberg R, et al.
2006.
Consumption of aspartame-containing beverages and incidence of
hematopoietic and brain malignancies.
Cancer Epidemiol Biomarkers Prev 15: 1654-1659.
Opperman JA. 1984.
Aspartame metabolism in animals.
In: Aspartame Physiology and Biochemistry (Stegink LD, Filer LJ Jr,
eds). New York: Dekker, 141-159.
Soffritti M. 2006.
Acesulfame Potassium: Soffritti responds. Letter to the Editor.
Environ Health Perspect 114 (9): A516-A517.
Soffritti M, Belpoggi F, Degli Esposti D, Lambertini L, Tibaldi E,
Rigano A 2006.
First experimental demonstration of the multipotential carcinogenic
effects of aspartame administered in the feed to Sprague-Dawley rats.
Environ Health Perspect 114 (3): 379-385.
Soffritti M, Belpoggi F, Degli Esposti D, Lambertini L. 2005.
Aspartame induces lymphomas and leukaemias in rats.
Eur J Oncol 10: 107-116.
Soffritti M, Belpoggi F, Cevolani D, Guarino M, Padovani M, Maltoni C.
2002a.
Results of longterm experimental studies on the carcinogenicity of
methyl alcohol and ethyl alcohol in rats.
Ann NY Acad Sci 982: 46-69.
Soffritti M, Belpoggi F, Lambertini L, Lauriola M, Padovani M, Maltoni
C. 2002b.
Results of longterm experimental studies on the carcinogenicity of
formaldehyde and acetaldehyde in rats.
Ann NY Acad Sci 982: 87-105.
Soffritti M, Belpoggi F, Padovani M, Lauriola M, Degli Esposti D,
Minardi F. 2004.
Life-time carcinogenicity bioassay of toluene given by stomach tube to
Sprague-Dawley rats.
Eur J Oncol 9: 91-102.
Stegink LD. 1984.
Aspartate and glutamate metabolism.
In: Aspartame Physiology and Biochemistry (Stegink LD, Filer LJ Jr,
eds). New York: Dekker, 47-76.
pages 18--24 [ Tables and Figures not copied ]
///////////////////////////////////////////////////////////
http://groups.yahoo.com/group/aspartameNM/message/1440
praise for second aspartame cancer rat study by Ramazzini Foundation,
Morando Soffritti et al, by informed MDs -- Blaylock, Landigan,
Walton, Roberts: Martini: Murray 2007.06.15
second large Ramazzini study on low dose lifetime aspartame in rats
confirms carcinogenicity -- Morando Soffritti will give data and get
Selikoff award April 23 at Mount Sinai School of Medicine in NYC:
Murray 2007.04.19
http://groups.yahoo.com/group/aspartameNM/message/1415 http://groups.yahoo.com/group/aspartameNM/message/1250
aspartame causes cancer in rats at levels approved for humans,
Morando Soffritti et al, Ramazzini Foundation, Italy &
National Toxicology Program
of National Institute of Environmental Health Sciences
2005.11.17 Env. Health Pers. 35 pages: Murray
http://groups.yahoo.com/group/aspartameNM/message/1226
USA National Institutes of Health National Toxicology
Program aids eminent Ramazzini Foundation, Bologna, Italy,
in more results on cancers in rats from lifetime low levels
of aspartame (methanol, formaldehyde), Felicity Lawrence,
www.guardian.co.uk: Murray 2005.09.30
http://groups.yahoo.com/group/aspartameNM/message/1186
aspartame induces lymphomas and leukaemias in rats, full plain text,
M Soffritti, F Belpoggi, DD Esposti, L Lambertini: Ramazzini
Foundation study 2005.07.14: main results agree with their previous
methanol and formaldehyde studies: Murray 2005.09.03
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 2005.07.27
http://groups.yahoo.com/group/aspartameNM/message/1016
President Bush & formaldehyde (aspartame) toxicity:
Ramazzini Foundation carcinogenicity results Dec 2002:
Soffritti: Murray 2003.08.03 rmforall
p. 88 "The sweetening agent aspartame hydrolyzes in the
gastrointestinal tract to become free methyl alcohol,
which is metabolized in the liver
to formaldehyde, formic acid, and CO2. (11)"
Medinsky MA & Dorman DC. 1994; Assessing risks of low-level
methanol exposure. CIIT Act. 14: 1-7.
Ann N Y Acad Sci. 2002 Dec; 982: 87-105.
Results of long-term experimental studies on the carcinogenicity of
formaldehyde and acetaldehyde in rats.
Soffritti M, Belpoggi F, Lambertin L,
Lauriola M, Padovani M, Maltoni C.
Cancer Research Center, European Ramazzini Foundation for Oncology
and Environmental Sciences, Bologna, Italy.
crcfr@ramazzini.it
Formaldehyde was administered for 104 weeks in drinking water
supplied ad libitum at concentrations of
1500, 1000, 500, 100, 50, 10, or 0 mg/L
to groups of 50 male and 50 female Sprague-Dawley rats beginning at
seven weeks of age.
Control animals (100 males and 100 females) received tap water only.
Acetaldehyde was administered to 50 male and 50 female
Sprague-Dawley rats beginning at six weeks of age at concentrations of
2,500, 1,500, 500, 250, 50, or 0 mg/L.
Animals were kept under observation until spontaneous death.
Formaldehyde and acetaldehyde were found to produce an increase
in total malignant tumors in the treated groups
and showed specific carcinogenic effects on various organs and
tissues.
PMID: 12562630
Ann N Y Acad Sci. 2002 Dec; 982: 46-69.
Results of long-term experimental studies on the carcinogenicity of
methyl alcohol and ethyl alcohol in rats.
Soffritti M, Belpoggi F, Cevolani D,
Guarino M, Padovani M, Maltoni C.
Cancer Research Center, European Ramazzini Foundation for Oncology
and Environmental Sciences, Bologna, Italy.
crcfr@ramazzini.it
Methyl alcohol was administered in drinking water
supplied ad libitum at doses of
20,000, 5,000, 500, or 0 ppm to groups of male and female
Sprague-Dawley rats 8 weeks old at the start of the experiment.
Animals were kept under observation until spontaneous death.
Ethyl alcohol was administered by ingestion in drinking water at a
concentration of 10% or 0% supplied ad libitum to groups of male and
female Sprague-Dawley rats; breeders and offspring were included in
the experiment.
Treatment started at 39 weeks of age (breeders), 7 days before mating,
or from embryo life (offspring)
and lasted until their spontaneous death.
Under tested experimental conditions, methyl alcohol and ethyl alcohol
were demonstrated to be carcinogenic for various organs and tissues.
They must also be considered multipotential carcinogenic agents.
In addition to causing other tumors, ethyl alcohol induced malignant
tumors of the oral cavity, tongue, and lips.
These sites have been shown to be target organs in man by
epidemiologic studies.
Publication Types: Review Review, Tutorial PMID: 12562628
http://groups.yahoo.com/group/aspartameNM/message/1339
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/1335
Morando Soffritti of Ramazzini Foundation rebuts EFSA AFC critique,
www.laleva.org: Murray 2006.05.05
http://groups.yahoo.com/group/aspartameNM/message/1334
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
http://www.efsa.eu.int/press_room/pr...e/1472_en.html http://www.efsa.eu.int/science/afc/a...s/1471_en.html http://www.efsa.eu.int/press_room/me...tindex_en.html http://www.flyonthewall.com/FlyBroad...essConference/ http://www.efsa.eu.int/science/afc/a...rtame_en1.\pdf http://groups.yahoo.com/group/aspartameNM/message/1338
Aspartame: The healthy option? Richard A. Lovett, The New Scientist
2006.05.04: Murray 2006.05.08
http://groups.yahoo.com/group/aspartameNM/message/1302
The Lowdown on Sweet? (Ramazzini Foundation, M Soffritti proof that
aspartame causes cancers), Melanie Warner, The New York Times:
sucralose: Prof. DL Katz: Murray 2006.02.12
http://groups.yahoo.com/group/aspartameNM/message/1303
David L. Katz MD comments briefly with Diane Sawyer on ABC
Good Morning America re Ramazzini aspartame cancer study:
excellent opus at Yale U: mainstream research on aspartame
(methanol, formaldehyde, formic acid) toxicity: Murray 2006.02.14
///////////////////////////////////////////////////////////
http://groups.yahoo.com/group/aspartameNM/message/1070
critique of aspartame review, French Food Safety Agency AFSSA
2002.05.07 aspartamgb.pdf (18 pages, in English), Martin Hirsch:
Murray 2004.04.13
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 EU Scientific Committee on Food, a whitewash
http://groups.yahoo.com/group/aspartameNM/message/1045 http://www.holisticmed.com/aspartame...2-response.htm
Mark Gold exhaustively critiques European Commission Scientific
Committee on Food re aspartame ( 2002.12.04 ):
59 pages, 230 references
A very detailed, highly credible account of the dubious approval
process
for aspartame in July, 1981 is part of the just released two-hour
documentary "Sweet Misery, A Poisoned World: An Industry Case
Study of a Food Supply In Crisis" by Cori Brackett:
cori@soundandfuryproductions.com http://www.soundandfuryproductions.com/ 520-624-9710
2301 East Broadway, Suite 111 Tucson, AZ 85719
Mary Nash Stoddard
Toxicology Sourcebook: "Deadly Deception Story of Aspartame"
Aspartame Consumer Safety Network and Pilot Hotline [since 1987]
P.O. Box 2001 Frisco, Texas 75034 U.S. [ North of Dallas ]
Phone/FAX: 214.387.4001
marystod@airmail.net http://www.aspartamesafety.com http://www.aspartamesafety.com/en_espanol.htm http://www.sweetpoison.com/ http://www.issplendasafe.com/ http://www.sweetpoison.com/food-additives-to-avoid.html
Dr. Janet Starr Hull, PhD, CN
jshull@sweetpoison.com
Splenda®: Is It Safe Or Not?
http://www.truthinlabeling.org/ Truth in Labeling Campaign [MSG]
Adrienne Samuels, PhD The toxicity/safety of processed
free glutamic acid (MSG): a study in suppression of information.
Accountability in Research 1999; 6: 259-310. 52-page review
P.O. Box 2532 Darien, Illinois 60561
858-481-9333
adandjack@aol.com http://www.dorway.com/tldaddic.html 5-page review
Roberts HJ Aspartame (NutraSweet) addiction.
Townsend Letter 2000 Jan;
HJRobertsMD@aol.com http://www.sunsentpress.com/ sunsentpress@aol.com
Sunshine Sentinel Press P.O.Box 17799 West Palm Beach, FL 33416
800-814-9800 561-588-7628 561-547-8008 fax
http://groups.yahoo.com/group/aspartameNM/message/669
1038-page medical text "Aspartame Disease: An Ignored Epidemic"
published May 30 2001 $ 60.00 postpaid data from 1200 cases
available at
http://www.amazon.com
over 600 references from standard medical research
http://groups.yahoo.com/group/aspartameNM/message/790
Moseley: review Roberts "Aspartame Disease: An Ignored Epidemic":
Murray 2002.02.07 rmforall
Roberts, Hyman J., 1924- ,
Useful insights for diagnosis, treatment and public heath: an updated
anthology of original research, 2002, 798 pages,
aspartame disease, pages 627-685, 778-780
http://groups.yahoo.com/group/aspartameNM/message/859
Roberts: the life work of a brilliant clinician: aspartame toxicity:
Murray 2002.08.02 rmforall
Russell L. Blaylock, MD 601-982-1175 Madison, Mississippi
"Excitotoxins: The Taste that Kills", 1977, 298 p., 493 references.
"Health and Nutrition Secrets that can save your life", 2002, 459 p.,
558 + 30 references, $ 30
http://www.russellblaylockmd.com/ http://groups.yahoo.com/group/aspartameNM/message/1090
aspartame, MSG, excitotoxins, NMDA glutamate receptors,
multiple sclerosis: Blaylock: Murray 2004.06.09
http://groups.yahoo.com/group/aspartameNM/message/97
Lancet website aspartame letter 1999.07.29:
Excitotoxins 1999 Part 1/3 Blaylock: Murray 2000.01.14
The Medical Sentinel Journal 1999 Fall; (95 references)
http://www.dorway.com/blayenn.html http://groups.yahoo.com/group/aspartameNM/message/857 www.dorway.com: original documents and long reviews of flaws in
aspartame toxicity research: Murray 2002.07.31
http://groups.yahoo.com/group/aspartameNM/message/858
Samuels: Strong: Roberts: Gold: flaws in double-blind studies re
aspartame and MSG toxicity: Murray 2002.08.01
"Survey of aspartame studies: correlation of outcome and funding
sources," 1998, unpublished:
http://www.dorway.com/peerrev.html
Walton found 166 separate published studies in the peer reviewed
medical literature, which had relevance for questions of human safety.
The 74 studies funded by industry all (100 %) attested to aspartame's
safety, whereas of the 92 non-industry funded studies, 84 (91 %)
identified a problem. Six of the seven non-industry funded studies
that were favorable to aspartame safety were from the FDA, which
has a public record that shows a strong pro-industry bias.
Ralph G. Walton, MD, Prof. of Clinical Psychology, Northeastern Ohio
Universities, College of Medicine, Dept. of Psychiatry, Youngstown,
OH 44501, Chairman, The Center for Behavioral Medicine,
Northside Medical Center, 500 Gypsy Lane, P.O. Box 240
Youngstown, OH 44501 330-740-3621
rwalton193@aol.com http://www.neoucom.edu/DEPTS/Psychiatry/walton.htm http://groups.yahoo.com/group/aspartameNM/message/622
Gold: Koehler: Walton: Van Den Eeden: Leon:
aspartame toxicity: Murray 2001.06.04 four double-blind studies
http://groups.yahoo.com/group/aspartameNM/message/1077
eight depressed people react strongly to aspartame,
Prof. Ralph G. Walton, MD, 1993 double-blind study, full text:
Murray 2004.04.26
Walton, RG, "Adverse reactions to aspartame: double-blind challenge
in patients from a vulnerable population," 1993,
with Robert Hudak and Ruth J. Green-Waite,
rwalton193@aol.com
Biological Psychiatry, 34 (1), 13-17.
Ralph G. Walton, MD, Prof. of Clinical Psychology,
Northeastern Ohio Universities, College of Medicine,
Dept. of Psychiatry, Youngstown, OH 44501,
Chairman, The Center for Behavioral Medicine,
Northside Medical Center, 500 Gypsy Lane,
P.O. Box 240 Youngstown, OH 44501 330-740-3621
http://www.neoucom.edu/DEPTS/Psychiatry/walton.htm
Eight depressed patients, ages 24-60, and five non-depressed controls,
ages 24-56, employed at the hospital, were given for 7 days either
aspartame or a placebo, and then after a 3 day break, given the
opposite. Each got 2100 mg aspartame daily, 30 mg/kg bodyweight,
equal to 10-12 cans of diet soda daily, about a gallon. Despite the
very small number of subjects, the results were dramatic and
statistically significant. The eight depressed patients reported with
aspartame, compared to placebo, much higher levels of nervousness,
trouble remembering, nausea, depression, temper, and malaise.
(For each symptom, p<0.01)
The five normals did not report strong enough differences
between aspartame and placebo to be significant.
Initially, the study was to be on a group of 40, but was halted by the
Institutional Review Board because of severe reactions
among 3 of the depressed patients.
Again, statistical significance with only 8 depressed patients:
"In this study, patients most often began to report significant
symptoms after day 2 or 3." The incidence rate is very high,
indeed, about 1/3. The most common symptoms are entirely typical
of thousands of case histories.
http://groups.yahoo.com/group/aspartameNM/message/927
Donald Rumsfeld, 1977 head of Searle Corp.,
got aspartame FDA approval: Turner: Murray 2002.12.23
http://www.dorway.com/upipart1.txt http://groups.yahoo.com/group/aspartameNM/message/262
aspartame expose 96K Oct 1987 Part 1/3: Gregory Gordon,
UPI reporter: Murray 2000.07.10
http://www.dorway.com/enclosur.html http://groups.yahoo.com/group/aspartameNM/message/53
aspartame history Part 1/4 1964-1976: Gold: Murray 1999.11.06
http://groups.yahoo.com/group/aspartameNM/message/928
revolving door, Monsanto, FDA, EPA: NGIN: Murray 2002.12.23
///////////////////////////////////////////////////////////
http://groups.yahoo.com/group/aspartameNMmessage/1437
stevia to be approved and cyclamates limited by Food Standards
Australia New Zealand: JMC Geuns critiques of two recent stevia
studies by Nunes: Murray 2007.05.29
http://groups.yahoo.com/group/aspartameNM/message/1427
more from The Independent, UK, Martin Hickman, re ASDA
(unit of Wal-Mart Stores) and Marks & Spencer ban of aspartame,
MSG, artificial chemical additives and dyes to prevent ADHD in kids:
Murray 2007.05.16
http://news.independent.co.uk/uk/hea...cle2548747.ece http://groups.yahoo.com/group/aspartameNM/message/1426
ASDA (unit of Wal-Mart Stores WMT.N) and Marks & Spencer
will join Tesco and also Sainsbury to ban and limit aspartame,
MSG, artificial flavors dyes preservatives additives, trans fats,
salt "nasties" to protect kids from ADHD: leading UK media:
Murray 2007.05.15
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/1277
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
formaldehyde as a potent unexamined cofactor in cancer research --
sources include methanol, dark wines and liquors, aspartame, wood and
tobacco smoke: IARC Monographs on the Evaluation of Carcinogenic Risks
to Humans implicate formaldehyde in #88 and alcohol drinks in #96:
some related abstracts: Murray 2007.05.15
http://groups.yahoo.com/group/aspartameNM/message/1417
aspartame (methanol, formaldehyde) toxicity research summary:
Rich Murray 2007.06.16
http://groups.yahoo.com/group/aspartameNM/message/1404
One liter aspartame diet soda, about 3 12-oz cans,
gives 61.5 mg methanol,
so if 30% is turned into formaldehyde, the formaldehyde
dose of 18.5 mg is 37 times the recent EPA limit of
0.5 mg per liter daily drinking water for a 10-kg child:
http://www.epa.gov/teach/chem_summ/F...de_summary.pdf
2007.01.05 [ does not discuss formaldehyde from methanol
or aspartame ]
http://www.epa.gov/teach/teachsurvey.html comments
teach@environmentalhealthconsulting.com
"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 76 members, 1,441 posts in a public, searchable archive
http://RMForAll.blogspot.com http://groups.yahoo.com/group/aspartameNM/message/1340
aspartame groups and books: updated research review of
2004.07.16: Murray 2006.05.11
http://groups.yahoo.com/group/aspartameNM/message/1395
Aspartame Controversy, in Wikipedia democratic
encyclopedia, 72 references (including AspartameNM # 864
and 1173 by Murray), brief fair summary of much more
research: Murray 2007.01.01
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.
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
http://groups.yahoo.com/group/aspartameNM/message/1143
methanol (formaldehyde, formic acid) disposition:
Bouchard M et al, full plain text, 2001: substantial
sources are degradation of fruit pectins, liquors,
aspartame, smoke: Murray 2005.04.02
///////////////////////////////////////////////////////////
Lifetime exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats, Morando Soffritti et al, European Ramazzini Foundation, USA EPA Environmental Health Perspectives 2007.06.13 free full text 24 pages: Murray 
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