*******************************************************

http://groups.yahoo.com/group/aspartameNM/message/1310
Aspartame and smoking give the same toxic metabolite as does benzene,
Lin YS et al, U N Carolina, Chapel Hill, 2006 Jan.,
Center for Environmental Health and Susceptibility: Murray 2006.03.01

[ See also:
http://groups.yahoo.com/group/aspartameNM/message/1309
History and origin of benzene in soft drinks, Ross E. Getman, Esq,
Wash DC and NY State Bars, http://argentina.indymedia.org:
Murray 2006.03.01 ]


"Multiple linear regression models identified several significant
contributors to 1,4-BQ-Alb levels,
including gender,
body mass index (BMI),
the gender-BMI interaction,
automobile refuelling,
smoking status,
and consumption of fruit
and the artificial sweetener, aspartame.

The authors predicted that these background levels of 1,4-BQ-Alb
were equivalent to occupational exposures
between 1 and 3 parts per million of benzene.

Mixed effects linear models indicated that the random variation in
adduct levels was about equally divided between and within subjects.

The observations indicate that levels of 1,4-BQ-Alb cover a wide range
in the general population,
and they support the hypotheses that demographic,
diet and lifestyle factors are contributing sources."


1: Biomarkers. 2006 Jan-Feb; 11(1): 14-27.
Variability of albumin adducts of 1,4-benzoquinone,
a toxic metabolite of benzene, in human volunteers.
Lin YS, McKelvey W, Waidyanatha S, Rappaport SM.
Department of Environmental Sciences and Engineering,
University of North Carolina, Chapel Hill, NC, 27599, USA.
suramya.unc.edu; smr@...;

[ Co-authors in other relevant papers:

Lan Q qingl@...;
Greenland S lesdomes@... ;
Sandler RS rsandler@... ;
Golding BT b.t.golding@... ;
Smith MT martynts@...; ]

A putative haematotoxic and leukaemogenic metabolite of benzene,
1,4-benzoquinone (1,4-BQ), reacts rapidly with macromolecules.

The authors previously characterized levels of the albumin (Alb) adduct
(1,4-BQ-Alb) of this reactive species
in populations of workers exposed to benzene.

Since high levels of 1,4-BQ-Alb were also measured in unexposed
workers from those investigations,
the current study was initiated to determine potential sources
of 1,4-BQ in the general population.

A single blood sample was collected from 191 healthy subjects from
the Research Triangle area, NC, USA,
to determine the baseline 1,4-BQ-Alb levels and contributing sources.

The median 1,4-BQ-Alb at baseline was
550?pmol?g(-1) Alb (interquartile range 435-814?pmol?g(-1)).

A second blood sample was collected approximately 3 months later
from a subgroup of 33 subjects to estimate
the within- and between-person variation in 1,4-BQ-Alb.

Standardized questionnaires were administered to collect information
about demographic, dietary and lifestyle factors.

Multiple linear regression models identified several significant
contributors to 1,4-BQ-Alb levels,
including gender,
body mass index (BMI),
the gender-BMI interaction,
automobile refuelling,
smoking status,
and consumption of fruit
and the artificial sweetener, aspartame.

The authors predicted that these background levels of 1,4-BQ-Alb
were equivalent to occupational exposures
between 1 and 3 parts per million of benzene.

Mixed effects linear models indicated that the random variation
in adduct levels was about equally divided between and within subjects.

The observations indicate that levels of 1,4-BQ-Alb
cover a wide range in the general population,
and they support the hypotheses that demographic,
diet and lifestyle factors are contributing sources.
PMID: 16484134
Feb 13 2006 12:53:38


http://www.sph.unc.edu/cehs/about/index.htm

Center for Environmental Health and Susceptibility
Overview
The goal of this Center is to bring together a broad group of
environmental health researchers to understand the mechanistic basis
of chemical toxicity and integrate this knowledge with epidemiology
in order to reduce the burden of environmental disease.

http://www.sph.unc.edu/cehs/research/exposure.htm

Exposure and Biomarkers Research Core (E&BRC)
Overview
Exposures to toxic substances vary greatly within and between persons
in a particular town or city. Such variability can impact the risks of
health effects associated with exposures, due to uneven distribution of
exposure across the population as well as to changes in exposure levels
that a given person experiences from day to day.
Since health effects linked to xenobiotic substances reflect the combined
effects of exposure and genetic factors, exposure variability
also creates problems in elucidating the impact of genetic susceptibility.
For example, persons genetically predisposed to produce small
amounts of a detoxifying enzyme are not at increased risk
if exposure levels are sufficiently low to prevent metabolic saturation,
while persons producing large amounts of the enzyme may be at
increased risk at levels of exposure high enough to saturate the metabolic
system. Studying relationships between exposure and biomarker levels in
human populations allows us to evaluate interindividual variability in rates
of uptake, distribution, metabolism and repair of toxic chemicals in the
body. The Exposure and Biomarker Research Core investigates such
exposure-biomarker relationships and thereby enhances our
understanding the underlying connections between environmental
exposures and health effects.
It combines toxicokinetic and stochastic models with measurements of
exposure and biomarkers in human studies, fostering collaboration and
sharing of ideas, data and methods among Center members.

Objectives:
to (1) support/expand collaborative research involving
exposure assessment and biomarkers of exposure and effect
in human studies;
(2) establish effective mechanisms for sharing ideas
within the E&BRC and with other relevant scientists;
and (3) increase interactions with other Research and Facility Cores
to foster application of sound quantitative
principles in study designs of Center members.

http://www.sph.unc.edu/cehs/staff/index.htm
Exposure and Biomarkers Research Core
Director: Stephen M. Rappaport, Ph.D.; Environmental Sci and
Engineering, SPH stephen_rappaport@... Phone: 919-966-5017

Members: Louise Ball, Ph.D.; Environmental Sciences and Engineering,
SPH lmball@... Phone: 966-7306

Jiu-Chiuan Chen, M.D., Ph.D., Epidemiology, SPH
jcchen@... Phone: 962-2756

George Christakos, Ph.D.; Environmental Sci and Engineering, SPH
george_christakos@... Phone: 6-1767

Marilie D. Gammon, Ph.D.; Epidemiology, SPH
gammon@... Phone: 966-7421

Lawrence L. Kupper, Ph.D.; Biostatistics, SPH
kupper@... Phone: 966-7260

Dana Loomis, Ph.D.; Epidemiology, SPH
Dana.Loomis@... Phone: 966-7424

Leena A. Nylander-French, Ph.D.; Environmental Sci and Engineering,
SPH leena_french@... Phone: 6-3826

David Richardson, Ph.D., Epidemiology, SPH
david_richardson@... Phone: 962-2756

Jane C. Schroeder, D.V.M., Ph.D.; Epidemiology, SPH
jane_schroeder@... Phone: 6-7446

Marc L. Serre, Ph.D.; Environmental Sci and Engineering, SPH
marc_serre@... Phone: 966-7014; 966-1173

James A. Swenberg, D.V.M., Ph.D.; Environmental Science and
Engineering, Nutrition, and Pathology and Laboratory Medicine,
SPH and MED james_swenberg@... Phone: 6-6139

Carcinogenesis. 2005 Dec 8; [Epub ahead of print]
Using urinary biomarkers to elucidate dose-related patterns
of human benzene metabolism.
Kim S, Vermeulen R, Waidyanatha S, Johnson BA, Lan Q,
Rothman N, Smith MT, Zhang L, Li G, Shen M, Yin S, Rappaport SM.
School of Public Health, University of North Carolina,
Chapel Hill, NC 27599, USA.
*******************************************************

http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=15576619
free full text PDF (118K)

Science. Author manuscript; available in PMC 2005 October 17.
Published in final edited form as:
Science. 2004 December 3; 306(5702): 1774-1776.
doi: 10.1126/science.1102443.
Copyright notice and Disclaimer

Hematotoxicity in Workers Exposed to Low Levels of Benzene
Qing Lan,1* Luoping Zhang,2* Guilan Li,3 Roel Vermeulen,1
Rona S. Weinberg,4 Mustafa Dosemeci,1 Stephen M. Rappaport,5
Min Shen,1 Blanche P. Alter,1 Yongji Wu,6 William Kopp,7
Suramya Waidyanatha,5 Charles Rabkin,1 Weihong Guo,2
Stephen Chanock,1,8 Richard B. Hayes,1 Martha Linet,1
Sungkyoon Kim,5 Songnian Yin,3 Nathaniel Rothman,1?
and Martyn T. Smith,2?#

1 Division of Cancer Epidemiology and Genetics, National Cancer
Institute (NCI), National Institutes of Health (NIH),
Department of Health and Human Services (DHHS),
Bethesda, MD 20892, USA.
2 School of Public Health, University of California, Berkeley, CA
94720, USA.
3 Chinese Center for Disease Control and Prevention, Beijing, China.
4 New York Blood Center, Clinical Services,
White Plains, NY 10605, USA.
5 School of Public Health, University of North Carolina,
Chapel Hill, NC 27599, USA.
6 Peking Union Medical College, Beijing, China.
7 SAIC-Frederick, Inc., Frederick, MD 21702, USA.
8 Center for Cancer Research, NCI, NIH, DHHS,
Bethesda, MD 20892, USA.

# To whom correspondence should be addressed.
martynts@...
*These authors contributed equally to this work.
?These authors co-supervised this work.

The publisher's final edited version of this article is available at
Science.
See commentary "Toxicology. Factory study shows low levels of benzene
reduce blood cell counts." in Science, volume 306 on page 1665.

Abstract
Benzene is known to have toxic effects on the blood and bone marrow,
but its impact at levels below the U.S. occupational standard
of 1 part per million (ppm) remains uncertain.
In a study of 250 workers exposed to benzene,
white blood cell and platelet counts were significantly lower than
in 140 controls, even for exposure below 1 ppm in air.
Progenitor cell colony formation significantly declined
with increasing benzene exposure and
was more sensitive to the effects of benzene
than was the number of mature blood cells.
Two genetic variants in key metabolizing enzymes,
myeloperoxidase and NAD(P)H:quinone oxidoreductase,
influenced susceptibility to benzene hematotoxicity.
Thus, hematotoxicity from exposure to benzene
occurred at air levels of 1 ppm or less and may be particularly
evident among genetically susceptible subpopulations.



Benzene causes toxicity to the hematopoietic system (hematotoxicity)
and leukemia (1).
Exposure to benzene occurs worldwide to workers in the
oil, shipping, automobile repair, shoe manufacture, and other industries
and to the general public from cigarette smoke, gasoline,
and automobile emissions (2).
In addition to ongoing concern about health effects at or
below the current U.S. occupational standard of 1 ppm,
high environmental exposures in cities (3) have led to regulatory
consideration of the risks posed by benzene as an air pollutant.

Limitations in previous occupational studies evaluating hematotoxicity
at low levels of benzene exposure led us to perform a large
cross-sectional study with detailed exposure assessment
that measured lymphocyte subsets and colony formation
from progenitor cells
in addition to the standard blood-count analyses
reported in most previous investigations.
Because benzene is thought to lower blood cell counts
via metabolite effects on hematopoietic progenitor cells (4),
we also evaluated the influence of
genetic variants in cytochrome P4502E1 (CYP2E1)
and myeloperoxidase (MPO),
which metabolize benzene to toxic quinones and free radicals (5),
and NAD(P)H:quinone oxidoreductase (NQO1),
which protects against this toxicity (6, 7).

We compared 250 benzene-exposed shoe workers
with 140 unexposed age-and sex-matched controls
who worked in three clothes-manufacturing factories
in the same region near Tianjin, China.
Subjects were young (mean ± SD: 29.9 ± 8.4 years),
about two-thirds were female (table S1),
and shoe workers had been employed an average of 6.1 ± 2.9 years.
For each subject, individual benzene and toluene exposure
was monitored repeatedly up to 16 months before phlebotomy,
and postshift urine samples were collected from each subject (8, 9).
Subjects were categorized into four groups by mean benzene levels
measured during the month before phlebotomy
[controls, <1 ppm, 1 to <10 ppm, and >=10 ppm (Table 1)],
and more than 100 of the exposed workers
had exposures below 1 ppm.

All types of white blood cells (WBCs) measured in the Complete Blood
Count and platelets (9) were significantly decreased in workers
exposed to <1 ppm benzene compared to controls (Table 1).
Lymphocyte subset analysis showed significantly decreased
CD4+-T cells, CD4+/CD8+ ratio, and B cells.
Hemoglobin concentrations were decreased only
among workers exposed to >10 ppm.
Tests for a linear trend using benzene air level as a continuous
variable were significant for platelets and all WBC measures except
monocytes and CD8+-T cells (Table 1).
Adjustment for a range of potential confounders
had a negligible effect on the strength of the associations (9).

We then restricted the linear-trend analyses to workers exposed to <10
ppm benzene, excluding controls and higher exposed workers,
and found that inverse associations remained
for total WBCs (P = 0.013),
granulocytes (P = 0.02),
lymphocytes (P = 0.045),
B cells (P = 0.018),
and platelets (P = 0.0016).
To address the influence of past benzene exposure on these cell types,
we examined workers exposed to mean benzene <1 ppm
over the previous year (n = 60),
and a subset who also had <40-ppm-years lifetime cumulative
benzene exposure (n = 50),
and found that the above cell types were
decreased compared to controls (P < 0.05).
Finally, to exclude the effect of other potential exposures
on these associations, we identified a group of workers
exposed to <1 ppm benzene with negligible exposure to other solvents
(n = 30) (fig. S1) (9)
and found decreased levels of WBCs, granulocytes,
lymphocytes, and B cells compared to controls (P < 0.05).
These findings,
based on differentiated blood cell counts, provide evidence of
hematotoxicity in workers exposed to benzene at or below 1 ppm.

Because benzene affected nearly all blood cell types,
toxicity to progenitor cells was suspected.
A fraction of hematopoietic progenitor cells circulate in the bloodstream
in dynamic equilibrium with the bone marrow
and can be cultured in colony-forming assays to measure
their proliferative potential (10).
Using peripheral blood from 29 benzene-exposed workers
and 24 matched controls,
we examined the dose-dependent effects of benzene on
different types of progenitor cell colony formation
(CFU-GM, BFU-E, CFU-GEMM) (9).
Highly significant dose-dependent decreases in colony
formation from progenitor cells were observed (Fig. 1).
Further, benzene caused a greater proportional decrease
in colony formation than in levels of
differentiated WBCs and granulocytes
(compare Fig. 1, B and C, to Fig. 1A),
suggesting that early progenitor cells are more sensitive
than are mature cells to the hematotoxic effects of benzene.
This greater sensitivity of early progenitor cells is in agreement
with previous findings in human cell cultures and mice (11, 12).

Genetic variation in enzymes responsible for activating and
detoxifying benzene has been shown to confer susceptibility to benzene
poisoning in highly exposed workers (6, 13, 14).
We examined four nonsynonymous
single-nucleotide polymorphisms (SNPs),
with probable functional significance,
in the CYP2E1, MPO, and NQO1 genes (9).
Two genotypes significantly influenced WBC counts
in benzene-exposed workers,
MPO--463GG (rs2333227) (P = 0.04)
and NQO1 465CT (rs4986998) (P = 0.014)
(table S2).
In exposed subjects who carry either one (n = 191)
or both of the "at risk" genotypes (n = 11),
there was a strong gene-dosage effect
(Ptrend = 0.004) (table S3),
which was also present among those exposed to
<1 ppm (Ptrend = 0.003).
Compared to a mean ± SD WBC count of 5980 ± 1420
cells/microl among subjects with neither "at risk" genotype,
the WBC count was 5480 ± 1120 cells/microl among subjects
with either "at risk" genotype (P = 0.006)
and 4900 ± 1240 cells/microl (P = 0.039) for both genotypes,
in subjects exposed to <1 ppm.
Neither genotype was associated with WBC count in
controls, either separately (table S2)
or in combination (Ptrend = 0.94) (table S3),
and the trends in exposed workers and controls were
significantly different from each other (test for interaction, P = 0.03).
Subjects with the MPO--463GG genotype have normal expression
and had a greater decrease in WBC counts from benzene exposure
compared to individuals with the GA or AA genotypes
(the latter two being associated with reduced expression) (15).
The functional significance of the NQO1 465C>T SNP is less clear,
but it may increase alternative splicing and lower expression,
thereby enhancing benzene hematotoxicity, as we observed.
The other two SNPs
[CYP2E1--1053C>T (rs2031920)
and NQO1 609C>T (rs1800566)]
were not significantly related to WBCs (table S2).

There have been numerous studies of benzene-induced hematotoxicity
( www.epa.gov/iris/toxreviews/0276-tr.pdf ),
but few have been able to study effects at low levels of exposure.
Ward et al. (16) found no evidence of a threshold for hematotoxic
effects of benzene and suggested that exposure to <5 ppm benzene
could result in hematologic suppression.
Occupational exposure decreased WBCs in petrochemical workers
exposed to <10 ppm benzene (17),
and Qu et al. reported that WBCs and other cell types were decreased
in workers exposed to <5 ppm benzene (18).
In contrast, Collins et al. (19, 20) and Tsai et al. (21)
did not detect decreased blood cell counts based on
routine monitoring of workers exposed to low levels of benzene.

The present study showed that total WBCs, granulocytes, lymphocytes,
B cells, and platelets significantly declined with increasing benzene
exposure and were lower in workers exposed to benzene
at air levels of 1 ppm or less compared to controls.
Our findings are particularly robust because
we carried out extensive exposure assessment
over a 16-month period (8)
and linked individual air-monitoring data to the endpoints measured.
Further, we showed that benzene exposure decreased colony formation
from myeloid progenitor cells, and that these progenitors
were more sensitive to benzene toxicity than were mature WBCs.
Finally, genetic variation in MPO and NQO1
conferred susceptibility to benzene-induced lowering of WBC counts.
Although confirmation of these findings in other studies is needed,
these data provide evidence that benzene causes hematologic effects
at or below 1 ppm, particularly among susceptible subpopulations.

Footnotes

Supporting Online Material
www.sciencemag.org/cgi/content/full/306/5702/1774/DC1,
Materials and Methods, SOM Text, Fig. S1, Tables S1 to S3.,
References

References
1. Aksoy M. Environ Health Perspect. 1989; 82: 193. [PubMed]

2. Gist GL, Burg JR. Toxicol Ind Health. 1997; 13: 661. [PubMed]

3. Simon V, et al. Sci Total Environ. 2004; 334-335: 177.

4. Yoon BI, et al. Exp Hematol. 2001; 29: 278. [PubMed] [Full Text]

5. Ross D. Eur J Haematol Suppl. 1996; 60: 111. [PubMed]

6. Rothman N, et al. Cancer Res. 1997; 57: 2839. [PubMed]

7. Bauer AK, et al. Cancer Res. 2003; 63: 929.
[PubMed] [Free Full Text]

8. Vermeulen R, et al. Ann Occup Hyg. 2004; 48: 105.
[PubMed] [Full Text]

9. Materials and methods are available as supporting material
on Science Online.

10. Kreja L, Greulich KM, Fliedner TM, Heinze B.
Int J Radiat Biol. 1999; 75: 1241. [PubMed]

11. Smith MT, et al. Carcinogenesis. 2000; 21: 1485.
[PubMed] [Free Full Text]

12. Abernethy DJ, Kleymenova EV, Rose J, Recio L, Faiola B.
Toxicol Sci. 2004; 79: 82. [PubMed] [Free Full Text]

13. Wan J, et al. Environ Health Perspect. 2002; 110: 1213.
[Free Full text in PMC]

14. Xu JN, et al. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi.
2003; 21 :86. [PubMed]

15. Winterbourn CC, Vissers MC, Kettle AJ.
Curr Opin Hematol. 2000; 7: 53. [PubMed] [Full Text]

16. Ward E, et al. Am J Ind Med. 1996; 29: 247. [PubMed]

17. Zhang B. Zhonghua Yu Fang Yi Xue Za Zhi. 1996; 30: 164.
[PubMed]

18. Qu Q, et al. Am J Ind Med. 2002; 42: 275.
[PubMed] [Full Text]

19. Collins JJ, et al. J Occup Med. 1991; 33: 619. [PubMed]

20. Collins JJ, Ireland BK, Easterday PA, Nair RS, Braun J.
J Occup Environ Med. 1997; 39: 232. [PubMed] [Full Text]

21. Tsai SP, et al. Regul Toxicol Pharmacol. 2004; 40: 67.
[PubMed] [Full Text]

22. Zeger SL, Liang KY. Biometrics. 1986; 42: 121. [PubMed]

23. We thank the participants for taking part in this study.

Supported by NIH grants RO1ES06721, P42ES04705,
and P30ES01896 (M.T.S.), P42ES05948
and P30ES10126 (S.M.R.),
and NIH contract N01-CO-12400 with SAIC-Frederick, Inc.

M.T.S. has received consulting and expert testimony fees
from law firms representing both plantiffs and defendants
in cases involving exposure to benzene.

G.L. has received funds from the American Petroleum Institute for
consulting on benzene-related health research.

Figures and Tables
Fig. 1
Effect of benzene exposure on
(A) white blood cell (WBC) and granulocyte counts;
(B) colonies from the colony-forming unit-granulocyte-macrophage
(CFU-GM) and burst-forming unit-erythroid (BFU-E);
and (C) colonies from the colony-forming (more ...)

Table 1
Peripheral blood cell counts in relation to benzene exposure level.
There are up to 418 observations on 390 unique subjects
(140 controls and 250 benzene-exposed workers).
Data were obtained from 28 exposed subjects in both years
(2000 and 2001) and are (more ...)
*******************************************************

http://groups.yahoo.com/group/aspartameNM/message/1307
formaldehyde from 11% methanol part of aspartame or from red wine
causes same toxicity (hangover) harm: Murray 2006.03.01

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

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

http://groups.yahoo.com/group/aspartameNM/messages
group with 151 members, 1,310 posts in a public, searchable archive
http://RMForAll.blogspot.com http://AspartameNM.blogspot.com

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/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

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

http://groups.yahoo.com/group/aspartameNM/message/1291
European Food Safety Authority to decide aspartame safety by May:
caffeine diet drinks cause female hypertension, WC Winkelmayer et al,
JAMA 2005.11.09: PubMed lists 50 items for "diet soft drinks" since
2004 Oct.: Murray 2006.01.24

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

http://groups.yahoo.com/group/aspartameNM/message/939
aspartame (aspartic acid, phenylalanine) binding to DNA:
Karikas July 1998: Murray 2003.01.05 rmforall
Karikas GA, Schulpis KH, Reclos GJ, Kokotos G
Measurement of molecular interaction of aspartame and
its metabolites with DNA. Clin Biochem 1998 Jul; 31(5): 405-7.
Dept. of Chemistry, University of Athens, Greece
http://www.chem.uoa.gr gkokotos@...;
K.H. Schulpis inchildh@...; G.J. Reclos reklos@...;

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/925
aspartame puts formaldehyde adducts into tissues, Part 1/2
full text Trocho & Alemany 1998.06.26
Universitat Auṭnoma de Barcelona : Murray 2002.12.22

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/1106
hangover research relevant to toxicity of 11% methanol in aspartame
(formaldehyde, formic acid): Calder I (full text): Jones AW:
Murray 2004.08.05 rmforall

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

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

http://groups.yahoo.com/group/aspartameNM/message/870
Aspartame: Methanol and the Public Interest 1984: Monte:
Murray 2002.09.23

Humans suffer "toxic syndrome" (54) at a minimum lethal dose
of <1 gm/kg, much less than that of monkeys, 3-6 g/kg (42, 59).

The minimum lethal dose of methanol
in the rat, rabbit, and dog is 9.5, 7.0 , and 8.0 g/kg, respectively (43);
ethyl alcohol is more toxic than methanol to these test animals (43)."

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:
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/1304
to DL Katz MD, Yale U: M. Soffritti, Ramazzini F., did not mention that
humans are about 10X more vulnerable to aspartame than are rats:
found methanol and formaldehyde carcinogenicity 2002: human ADI
levels must be reduced hugely: Katz: Murray 2006.02.15

http://groups.yahoo.com/group/aspartameNM/message/1306
ban aspartame speech, Roger Williams MP, UK Parliament
2005.12.14: www.TheyWorkForYou.com: Murray 2006.02.20

As a medical layman, I suggest that evidence mandates immediate
exploration of the role of these ubiquitious, potent formaldehyde
sources as co-factors in epidemiology, research, diagnosis,
and treatment in a wide variety of disorders.

Folic acid, from fruits and vegetables, plays a role by powerfully
protecting against methanol (formaldehyde) toxicity.

Many common drugs, such as aspirin, interfere with folic acid,
as do some mutations in relevant enzymes.

The majority of aspartame reactors are female.

In mutual service, Rich Murray
*******************************************************