[Toxicology] 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 2007.04.30

Rich Murray via toxicol%40net.bio.net (by rmforall from comcast.net)
Thu May 3 18:55:05 EST 2007


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 2007.04.30
http://groups.yahoo.com/group/aspartameNM/message/1417

[ See also:

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  ]


" Absorbed formaldehyde can be oxidized to formate and carbon dioxide
or can be incorporated into biologic macromolecules. "

[ References include:  Soffritti M, Belpoggi F, Lambertini L, Lauriola
M, Padovani M, Maltoni C. 2002. Results of long-term experimental
studies on the carcinogenicity of formaldehyde and acetaldehyde in
rats. Ann NY Acad Sci 982:87-105.

Soffritti M, Maltoni C, Maffei F, Biagi R. 1989. Formaldehyde: an
experimental multipotential carcinogen. Toxicol Ind Health 5:699-730.
"

Morando Soffritti is a member of the Working Group. ]


http://www.ehponline.org/members/2005/7542/7542.html  free full text

After a thorough discussion of the epidemiologic, experimental, and
other relevant data, the working group concluded that formaldehyde is
carcinogenic to humans, based on sufficient evidence in humans and in
experimental animals.

In the epidemiologic studies, there was sufficient evidence that
formaldehyde causes nasopharyngeal cancer, "strong but not sufficient"
evidence of leukemia, and limited evidence of sinonasal cancer.

The working group also concluded that 2-butoxyethanol and 1-tert-
butoxy-2-propanol are not classifiable as to their carcinogenicity to
humans, each having limited evidence in experimental animals and
inadequate evidence in humans.

These three evaluations and the supporting data will be published as
Volume 88 of the IARC Monographs.  PMID: 16140628


 Environ Health Perspect. 2005 Sep; 113(9): 1205-8.
    Meeting report: summary of IARC monographs on formaldehyde, 2-
butoxyethanol, and 1-tert-butoxy-2-propanol.

        * Cogliano VJ,  Vincent James Cogliano  cogliano from iarc.fr,
        * Grosse Y,  Yann Grosse  grosse from iarc.fr,
        * Baan RA,   Robert A. Baan  baan from iarc.fr,
        * Straif K,  Kurt Straif,  straif from iarc.fr,
        * Secretan MB,  Marie Béatrice Secretan  secretan from iarc.fr,
        * El Ghissassi F,   Fatiha El Ghissassi  elghissassi from iarc.fr,
        * Working Group for Volume 88.


http://monographs.iarc.fr/ENG/Staff/index.php
photo of Carcinogen Identification and Evaluation Group - Staff

Secretariat: Tel. +33 (0)4 72 73 85 07  Fax +33 (0)4 72 73 83 19

Head of Programme,  Vincent James Cogliano

Secretary,  Helene Lorenzen-Augros

Scientists:
Robert Baan (genetic toxicology)
Fatiha El Ghissassi (biochemistry/genetic toxicology)
Yann Grosse (carcinogenesis/bioassays)
Béatrice Secretan (molecular toxicology)
Kurt Straif (epidemiology)

Technical Assistants:
Sandrine Egraz
Martine Lézère
Jane Mitchell

IARC, 150 Cours Albert Thomas, 69372 Lyon CEDEX 08, France
Tel: +33 (0)4 72 73 84 85 - Fax: +33 (0)4 72 73 85 75
© IARC 2004 - All Rights Reserved
http://monographs.iarc.fr   cie from iarc.fr,

Monographs Recently Published

IARC Monographs Vol 88
Formaldehyde, 2-Butoxyethanol and 1-tert-Butoxypropan-2-ol

December 2006
478 pages
ISBN 92 832 1288 6
US$ 40

This volume re-evaluates the available evidence on the carcinogenic
potential of formaldehyde, a substance that is found in the workplace
and in the environment.
Formaldehyde is widely used in resins that bind wood products, pulp
and paper; in glasswool and rockwool insulation; in plastics and
coatings, textile finishing, chemical manufacture; and as a
disinfectant and preservative. Also evaluated are two glycol ethers, 2-
butoxyethanol and 1-tert-butoxypropan-2-ol, which are widely used as
solvents in paints and paint thinners, coatings, glass and surface
cleaners, inks, adhesives, personal-care products, and as chemical
intermediates.
As for formaldehyde, there is sufficient evidence in epidemiological
studies for nasopharyngeal cancer, strong but not sufficient evidence
for leukaemia, and limited evidence for sinonasal cancer.
The extensive scientific database on the mechanisms by which
formaldehyde can induce nasal-tract cancer in humans is considered.
These data provide strong support for the empirical observation of
nasopharyngeal cancer in humans.
In contrast, the lack of information on possible mechanisms by which
formaldehyde might increase the risk for leukaemia in humans tempered
the interpretation of the epidemiological data on that cancer.
Although this volume focuses on a qualitative assessment of the
carcinogenic potential of formaldehyde, subsequent predictions of the
risks for nasopharyngeal cancer should consider pertinent information
on mechanisms of carcinogenesis, including genotoxicity and dose-
dependent cytoxicity.
A theme common to the three evaluations is the consideration of
mechanistic information to develop and evaluate hypotheses on the
sequence of steps that lead to the induction of tumours in
experimental animals.
The hypothesized mechanisms described provide an interesting set of
cases that range from a vast literature on respiratory tract tumours
in rats induced by the inhalation of formaldehyde to some more
tentative hypotheses on the various tumours observed in animals
following exposure to both glycol ethers.
Recurring issues were the criteria that characterize a rare tumour or
how to introduce additional information to resolve difficult
questions; for example, how to consider the results of historical
controls.

    International Agency for Research on Cancer, Lyon, France.

    An international, interdisciplinary working group of expert
scientists met in June 2004 to develop IARC Monographs on the
Evaluation of the Carcinogenic Risk of Chemicals to Humans (IARC
Monographs) on formaldehyde, 2-butoxyethanol, and 1-tert-butoxy-2-
propanol.

Each IARC Monograph includes a critical review of the pertinent
scientific literature and an evaluation of an agent's potential to
cause cancer in humans.

Key words: 1-tert-butoxy-2-propanol, 2-butoxyethanol, carcinogen,
formaldehyde, glycol ethers, hazard identification, IARC Monographs,
leukemia, nasopharyngeal cancer, sinonasal cancer. Environ Health
Perspect 113: 1205-1208 (2005) . doi:10.1289/ehp.7542 available via
http://dx.doi.org/ [Online 12 May 2005]

    Address correspondence to V.J. Cogliano, Carcinogen Identification
and Evaluation, International Agency for Research on Cancer, 150 cours
Albert Thomas, 69372 Lyon cedex 08, France.
Telephone: 33-4-72-73-84-76. Fax: 33-4-72-73-83-19. E-mail:
cogliano from iarc.fr,

    The Working Group for Volume 88 of the IARC Monographs includes:
Ulrich Andrae (Germany) ,  andrae from gsf.de,  Dr. Ulrich Andrae, GSF-
Institut für Toxikologie,. Postfach 1129, D-85758 Neuherberg, Germany
Fax: 149-089-3187-3449
Sherwood Burge (UK) ,
Rajendra S Chhabra (USA) ,  http://dir.niehs.nih.gov/dirtob/chhabra.htm
chhabrar from niehs.nih.gov,  General Toxicology Group, TOB, ETP, DIR
John Cocker (UK) ,   Health and Safety Laboratory, Buxton, UK
john.cocker from hsl.gov.uk,
David N Coggon (UK) ,   MRC Environmental Epidemiology Unit at the
University of Southampton, UK  dnc from mrc.soton.ac.uk,
Rory Conolly (USA) ,  Rconolly from ciit.org, Senior Research Biologist,
National Center for Computational Toxicology, Office of Research and
Development, U.S. Environmental Protection Agency
Paul Demers (Canada) , pdemers from unixg.ubc.ca,  Occupational Hygiene
Institute, University of British Columbia
David A Eastmond (USA) ,  david.eastmond from ucr.edu, Enviromental
Toxicology Graduate Program, University of California Riverside, CA
92521  (951) 827-4497 (Voice)  (951) 827-3087 (Fax)
Elaine Faustman (USA) , faustman from u.washington.edu, Professor, Env. and
Occ. Health Sciences, Adjunct Professor, Evans School 206-685-2269
Victor J Feron (the Netherlands) ,   TNO Nutrition and Food Research
(retired), The Netherlands TNO-CIVO TOXICOLOGY AND NUTRITION INSTITUTE
Utrechtseweg 48 3704 HE Zeist The Netherlands (31)-3404 44 144
Michel Gérin (Canada, Chair) , gerinm from ere.umontreal.ca,  Departement
de medecine du travail et d'hygiene du milieu, Universite de Montreal,
Quebec, Canada.
Marcel Goldberg (France) ,    marcel.goldberg from st-maurice.inserm.fr,
France -- National Institute of Health  and Medical Research INSERM
Unite 88, HNSM 14 Rue de Val d'Osne F-94410 St. Maurice France [33]
1-451-83859 [33] 1-451-83889
Departement Sante Travail, Institut de Veille Sanitaire, 12, rue du
Val d'Osne, 94410 Saint Maurice, France
Bernard D Goldstein (USA) ,  bdgold from pitt.edu,  Director of the
Environmental and Occupational Health Sciences Institute and Professor
and Chair of the Department of Environmental and Community Medicine at
UMDNJ - Robert Wood Johnson Medical School.  Dean's Office, University
of Pittsburgh Graduate School of Public Health, A624 Crabtree Hall,
130 DeSoto St., Pittsburgh, PA 15261, USA.
Roland  C Grafström (Sweden) ,   roland.grafstrom from imm.ki.se, Roland C
Grafström, Institute of Environmental Medicine, Karolinska Institutet,
Box 210, S−17177 Stockholm, Sweden
Telefax: +46-8−329402
Johnni Hansen (Denmark) ,  johnni from cancer.dk, PhD, Senior researcher,
Danish Cancer Registry , Institute of Cancer Epidemiology, Danish
Cancer Society, Strandboulevarden 49, DK-2100, Copenhagen, Denmark.
Michael Hauptmann (USA) ,   The National Cancer Institute
Kathy Hughes (Canada) ,   Head, Existing Substances Section 1,  Health
Canada,
Ted Junghans (USA) ,  tjunghans from tech-res.com,   Technical Resources
International, Inc., 6500 Rock Spring Drive, Suite 650, Bethesda, MD
20817, USA.
Dan Krewski (Canada) , MHA, MSc, PhD  dkrewski from uottawa.ca,  Professor
Director, R. Samuel McLaughlin Centre for Population Health Risk
Assessment, Institute of Population Healt, 1 Stewart Street, Room 320,
Phone: (613) 562-5381  Fax: (613) 562-5380
Steve Olin (USA) ,  solin from ilsi.org, ILSI  International Life Sciences
Institute
Martine Reynier (France) ,  martine.reynier from inrs.fr,  Mme Martine
REYNIER, Institut National de Recherche et de Sécurité (INRS), 30, rue
Olivier Noyer, 75680 Paris Cedex 14 (France) Tel : +33 (0)1 40 44 30
81  Fax : +33 (0)1 40 44 30 54
Judith Shaham (Israel) ,  yshaham from bezeqint.net,   Occupational Cancer
Department, National Institute of Occupational and Environmental
Health, Raanana, Israel.   MD, Occupational Cancer Unit, Occupational
Health & Rehabilitation Institute, P.O. Box 3, Raanana 43100, ISRAEL

Morando Soffritti (Italy) ,  crcfr from ramazzini.it,  European Foundation
of Oncology and Environmental Sciences "B. Ramazzini", Cesare Maltoni
Cancer Research Center, Bologna, Italy

Leslie Stayner (USA) ,  lstayner from uic.edu, Division of Epidemiology and
Biostatistics, University of Illinois at Chicago School of Public
Health (M/C 923), 1603 West Taylor Street, Room 971, Chicago, IL
60612. E-mail:
Patricia Stewart (USA) ,    National Food Safety and Toxicology
Center, 165 Food Safety and Toxicology Building, Michigan State
University, East Lansing, MI 48824; fax (517) 432-2310
Douglas Wolf (USA) ,  wolf.doug from epa.gov, DVM, PhD, USEPA,
(Toxicology)

    We gratefully acknowledge the important contributions of the
administrative staff of the IARC Monographs: S. Egraz, M. Lézère, J.
Mitchell, and E. Perez.

    The IARC Monographs are supported, in part, by grants from the
U.S. National Cancer Institute, the European Commission, the U.S.
National Institute of Environmental Health Sciences, and the U.S.
Environmental Protection Agency.

    The authors declare they have no competing financial interests.

    Received 31 August 2004 ; accepted 12 May 2005.

Introduction

Twenty-six scientists from 10 countries met at the International
Agency for Research on Cancer (IARC) in June 2004 to develop IARC
Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to
Humans (IARC Monographs) on formaldehyde, 2-butoxyethanol, and 1-tert-
butoxy-2-propanol (IARC, in press). This is the fourth IARC evaluation
of formaldehyde and the first of the glycol ethers.

Formaldehyde is widely used in resins that bind wood products, pulp
and paper, and glasswool and rockwool insulation. It is also used in
plastics and coatings, textile finishing, and chemical manufacturing
and as a disinfectant and preservative. High concentrations can be
found in some work environments, and much lower concentrations in
homes.

2-Butoxyethanol is a glycol ether widely used as a solvent in paints,
paint thinners, glass-cleaning and surface-cleaning products
(especially in the printing and silk-screening industries), and
personal-care and other personal products and as a chemical
intermediate. General-population exposure can occur through the use of
consumer products, particularly cleaning agents.

1-tert-Butoxy-2-propanol is a glycol ether that has found increasing
use as a solvent in coatings, glass-cleaning and surface-cleaning
products, inks, adhesives, and nail-polish lacquers.

Materials and Methods

IARC convenes an international, interdisciplinary working group of
expert scientists to develop each volume of the IARC Monographs. The
working group writes a critical review of the pertinent scientific
literature (published articles, articles accepted for publication, and
publicly available documents from government agencies) and a consensus
evaluation of each agent's potential to cause cancer in humans.

The IARC Monographs are developed during an 8-day meeting whose
objectives are review and consensus. Before the meeting, each member
of the working group writes a portion of the critical review. At the
meeting, four subgroups (exposure, cancer in humans, cancer in
experimental animals, and mechanistic and other relevant data) review
these drafts and develop consensus subgroup drafts. Then the working
group meets in plenary session to review the subgroup drafts and
develop a consensus evaluation. After the meeting, IARC scientists
review the final draft for accuracy and clarity before publication.

The evaluation is developed in steps (IARC 2005). The subgroup of
epidemiologists proposes an evaluation of the evidence of cancer in
humans as sufficient evidence, limited evidence, inadequate evidence,
or evidence suggesting lack of carcinogenicity. A subgroup of
toxicologists and pathologists proposes an evaluation of the evidence
of cancer in experimental animals, choosing one of the same
descriptors. Combination of these two partial evaluations yields a
preliminary default evaluation that the agent is one of the following:
group 1, carcinogenic to humans;
group 2A, probably carcinogenic to humans;
group 2B, possibly carcinogenic to humans;
group 3, not classifiable as to its carcinogenicity to humans; or
group 4, probably not carcinogenic to humans.

When the epidemiologic evidence is sufficient, the final evaluation is
carcinogenic to humans, regardless of the experimental evidence. In
other cases, the mechanistic and other relevant data are considered to
determine whether the default evaluation should be modified upward or
downward. A subgroup of experts in cancer mechanisms assesses the
strength of the mechanistic data and whether the mechanisms of tumor
formation in experimental animals can operate in humans. The overall
evaluation is a matter of scientific judgment, reflecting the combined
weight of the evidence.

Working groups are selected to invite the best-qualified experts and
to avoid real or apparent conflicts of interests. Consideration is
given also to demographic diversity and a balanced representation of
all scientific views. Each potential participant submits a Declaration
of Interests [World Health Organization (WHO) 2005], which IARC
assesses to determine whether there is a conflict that warrants some
limitation on participation. An expert with a real or apparent
conflict of interest may not serve as chairperson, draft text
discussing cancer data, or participate in the evaluations. IARC
strives to ensure that the working group is free from all attempts at
interference, before and during the meeting. This includes lobbying,
written materials, and meals or other favors offered by interested
parties. Working group members are asked not to discuss the subject
matter with anyone outside the meeting and to report all attempts at
interference (Cogliano et al. 2004).

Results

Formaldehyde.

There was a statistically significant excess of deaths from
nasopharyngeal cancer in the largest and most informative cohort study
of industrial workers (Hauptmann et al. 2004), with statistically
significant exposure-response relationships for peak and cumulative
exposure.

An excess of deaths from nasopharyngeal cancer was also observed in a
proportionate mortality analysis of the largest U.S. cohort of
embalmers (Hayes et al. 1990),
and an excess of cases of nasopharyngeal cancer was observed in a
Danish study of proportionate cancer incidence among workers at
companies that manufactured or used formaldehyde (Hansen and Olsen
1995).

Although other cohort studies reported fewer cases of nasopharyngeal
cancer than expected (Coggon et al. 2003; Pinkerton et al. 2004;
Walrath and Fraumeni 1983), the working group noted that the deficits
were small and the studies had low power to detect an effect on
nasopharyngeal cancer.

Of seven case-control studies of nasopharyngeal cancer (Armstrong et
al. 2000; Hildesheim et al. 2001; Olsen et al. 1984; Roush et al.
1987; Vaughan et al. 1986, 2000; West et al. 1993), five found
elevations of risk for exposure to formaldehyde.

The working group considered it "improbable that all of the positive
findings for nasopharyngeal cancer that were reported from the
epidemiologic studies, and particularly from the large study of
industrial workers in the United States, could be explained by bias or
unrecognized confounding effects." The working group concluded that
these studies provide "sufficient epidemiological evidence that
formaldehyde causes nasopharyngeal cancer in humans."

Excess mortality from leukemia, primarily of the myeloid type, has
been observed relatively consistently in six of seven studies of
embalmers, funeral parlor workers, pathologists, and anatomists (Hall
et al. 1991; Hayes et al. 1990; Levine et al. 1984; Logue et al. 1986;
Stroup et al. 1986; Walrath and Fraumeni 1983, 1984).

A recent meta-analysis found that, overall, the relative risk for
leukemia in these workers was increased and did not vary significantly
among studies (Collins and Lineker 2004).

There had been speculation that these findings might be explained by
viruses; however, the working group found little evidence that these
occupations have a higher incidence of viral infections or that
viruses have a causal role in myeloid leukemia.

Until recently, these leukemia findings received little attention
because excess leukemia had not been observed in the studies of
industrial workers.

There is now, however, some evidence for an association between
formaldehyde exposure and leukemia in the recent updates of two of the
three major industrial cohorts. A statistically significant exposure-
response relationship was observed for leukemia and, particularly, for
myeloid leukemia in the study of industrial workers in the United
States, based on peak exposure and, to a lesser degree, on average
intensity of exposure to formaldehyde (Hauptmann et al. 2003).

There was no excess mortality from leukemia when the industrial
workers were compared with the general U.S. population, but a
comparison with the general population may be biased.

In another study, excess mortality from leukemia was found in the
recent update of garment workers in the United States (Pinkerton et
al. 2004). This excess was statistically significant among workers
with a longer duration of exposure and follow-up.

In contrast, the updated study of industrial workers in the United
Kingdom did not find excess mortality from leukemia (Coggon et al.
2003). This high-quality study had sufficient size and follow-up to
have reasonable power for detecting an excess of leukemia, but it did
not report on peak exposures or the risk of myeloid leukemia
specifically.

The working group concluded, "In summary, there is strong but not
sufficient evidence for a causal association between leukaemia and
occupational exposure to formaldehyde." This conclusion, falling
between sufficient and limited evidence, was based on a consistently
increased risk in studies of embalmers, funeral parlor workers,
pathologists, and anatomists and was present in two of the three most
informative studies of industrial workers.

Several case-control studies have investigated the relationship
between formaldehyde exposure and sinonasal cancer. A pooled analysis
of 12 studies showed an increased risk of adenocarcinoma in men and
women thought never to have been exposed to wood dust or leather dust,
with an exposure-response trend for an index of cumulative exposure
(Luce et al. 2002).

One other case-control study (Olsen and Asnaes 1986) and a
proportionate incidence study (Hansen and Olsen 1995) showed an
increased risk of sinonasal cancer, particularly squamous cell
carcinoma.

Against these largely positive findings, the three most informative
cohort studies of industrial workers showed no excesses of sinonasal
cancer (Coggon et al. 2003; Hauptmann et al. 2004; Pinkerton et al.
2004).

The working group noted that most studies did not distinguish tumors
as originating in the nose or sinuses; thus, an increased risk of
nasal cancer would be diluted if there were no corresponding effect on
the sinuses.

In the case-control studies, the working group also noted the
potential for confounding by wood dust exposure, which is associated
with adenocarcinoma.

The working group concluded that there is limited evidence that
formaldehyde causes sinonasal cancer in humans.

In experimental animals, several studies have shown that inhalation
exposure induces squamous cell carcinomas of the nasal cavities in
rats (Albert et al. 1982; Feron et al. 1988; Gibson 1984; Kamata et
al. 1997; Kerns et al. 1983; Monticello et al. 1996; Morgan et al.
1986; Sellakumar et al. 1985; Woutersen et al. 1989), although single
studies in mice (Kerns et al. 1983) and hamsters (Dalbey 1982) showed
no carcinogenic effects.

Four studies of formaldehyde administered to rats in drinking water
gave varying results:
One showed an increased incidence of forestomach papillomas in male
rats (Takahashi et al. 1986);
a second showed an increased incidence of gastrointestinal
leiomyosarcomas in female rats and in both sexes combined (Soffritti
et al. 1989);
a third showed increased incidences of total malignant tumors,
lymphomas and leukemias, and testicular interstitial-cell adenomas in
male rats (Soffritti et al. 2002);
whereas a fourth did not show a carcinogenic effect (Til et al.
1989).

Formaldehyde also showed co-carcinogenic effects by inhalation,
ingestion, and dermal exposure (Dalbey 1982; Iverson 1986; Takahashi
et al. 1986).

The toxicokinetics of inhaled formaldehyde have been well studied
(Agency for Toxic Substances and Disease Registry 1999).

More than 90% of inhaled formaldehyde is absorbed in the upper
respiratory tract (Heck et al. 1985).

Absorbed formaldehyde can be oxidized to formate and carbon dioxide or
can be incorporated into biologic macromolecules.

Formaldehyde has a half-life of about 1 min in rat plasma (Rietbrock
1965).

Inhalation exposure has not been found to alter the endogenous
concentration of formaldehyde in the blood of rats, monkeys, or humans
(Casanova et al. 1988; Heck et al. 1983, 1985).

Oral exposure to 14C-formaldehyde resulted in some excretion in urine
and feces within 12 hr (Galli et al. 1983).

Dermal application of 14C-formaldehyde resulted in some urinary
excretion in rats and monkeys (Jeffcoat et al. 1983).

Evidence shows that formaldehyde is genotoxic in multiple in vitro
models and in exposed humans and laboratory animals.

Human studies reported increased DNA-protein crosslinks in workers
exposed to formaldehyde (Shaham et al. 1996, 2003), and this is
consistent with studies in laboratory rats and monkeys.

Cellular proliferation increases considerably at concentrations > 6
ppm and amplifies the genotoxic effects of formaldehyde.

The working group concluded, "The current data indicate that both
genotoxicity and cytotoxicity play important roles in the
carcinogenesis of formaldehyde in nasal tissues."

On the other hand, with respect to the potential for formaldehyde to
induce leukemia, the working group was not aware of any good rodent
models for acute myeloid leukemia in humans.

Several possible mechanisms were considered, such as clastogenic
damage to circulating stem cells.

There is a single study reporting cytogenetic abnormalities in the
bone marrow of rats inhaling formaldehyde (Kitaeva et al. 1990).

The working group concluded, "Based on the data available at this
time, it was not possible to identify a mechanism for the induction of
myeloid leukaemia in humans." This is an area needing more research.

The working group concluded that formaldehyde is carcinogenic to
humans (group 1), based on sufficient evidence in humans and
sufficient evidence in experimental animals.

Based on the information now available, this classification is higher
than those of previous IARC evaluations (IARC 1982, 1987, 1995).

2-Butoxyethanol.

2-Butoxyethanol was tested for carcinogenicity by inhalation exposure
in male and female mice and rats [National Toxicology Program (NTP)
2000]. Clear increases in tumor incidence were observed only in mice.
In male mice exposed to 2-butoxyethanol, there was a dose-related
increase in the incidence of hemangiosarcomas of the liver. In female
mice, there was a dose-related increase in the incidences of combined
forestomach squamous-cell papillomas and carcinomas (mainly
papillomas). In female rats, there was a positive trend in the
occurrence of benign or malignant pheochromocytomas (mainly benign) of
the adrenal medulla, but this equivocal result could not be attributed
with confidence to exposure to 2-butoxyethanol. No increases were
observed in male rats. The epidemiologic data were inadequate for this
compound.

Regarding mechanisms of carcinogenesis, the working group considered
that hemolysis and associated oxidative stress in the liver have been
proposed to be linked to the induction of mouse liver neoplasia. They
also considered that, in view of lower sensitivity to hemolysis of
human erythrocytes and higher human liver concentrations of the
antioxidant vitamin E, the induction of liver tumors in humans would
be improbable through this pathway, but it was noted that other
potential mechanisms have not been investigated. The working group
observed that the mouse forestomach tumors are associated with high
local exposure to 2-butoxyethanol and high local concentrations of the
toxic metabolite 2-butoxyacetic acid.

The working group concluded that 2-butoxyethanol is not classifiable
as to its carcinogenicity to humans (group 3), with limited evidence
in experimental animals and inadequate evidence in humans.

1-tert-Butoxy-2-propanol.

1-tert-Butoxy-2-propanol was tested for carcinogenicity by inhalation
exposure in male and female mice and rats (Doi et al. 2004; NTP 2003).
In a single study in both male and female mice, a dose-related
increase in the combined incidence of liver tumors (hepatocellular
adenomas and carcinomas), including hepatoblastomas, was observed.
When hepatocellular carcinomas and hepatoblastomas were combined,
there was a significant trend for the increase in malignant tumors in
females. In male rats, there were marginal, nonsignificant increases
in the incidences of renal tubule adenomas (with one carcinoma at the
highest dose) and hepatocellular adenomas, but these findings were
considered to be equivocal. In female rats, there were no dose-related
increases in tumor incidence. No epidemiologic data were available for
this compound.

With regard to mechanisms of carcinogenesis, the working group found
the available data inadequate to elucidate a potential mechanism for
the mouse liver tumors. They found the renal effects largely
consistent with the alpha2u-globulin-associated nephropathy that
occurs in male rats, but concluded that the available evidence
satisfies only some, but not all, of the IARC criteria for the
mechanism associated with accumulation of alpha2u-globulin. Regarding
the potential for genotoxic effects, the working group was not able to
draw any meaningful conclusion in view of the scarcity of the data
available.

The working group concluded that 1-tert-butoxy-2-propanol is not
classifiable as to its carcinogenicity to humans (group 3), with
limited evidence in experimental animals and inadequate evidence in
humans.

Discussion

A theme common to these three evaluations is the consideration of
mechanistic information to develop and evaluate hypotheses about the
sequence of steps leading to the induction of tumors in experimental
animals.

The hypothesized mechanisms described in these evaluations provide an
interesting set of cases that range from a vast literature on
respiratory-tract tumors in rats induced by inhalation of formaldehyde
to some more tentative hypotheses about the various tumors observed in
animals after exposure to glycol ethers.

Both types of mechanistic data sets were of use in the evaluation
process.

The evaluation of formaldehyde as carcinogenic to humans shows the
importance of mechanistic information in the classification of
carcinogens.

For the nasopharyngeal tumors, the working group discussed the
convergence of the epidemiologic, experimental, and mechanistic
evidence.

If the evidence in humans had been less than sufficient, the strong
mechanistic evidence in exposed humans and sufficient evidence in
experimental animals might still have led to classification as group
1.

The extensive mechanistic data for formaldehyde-induced respiratory
cancer provide strong support for the empirical observation of
nasopharyngeal cancer in humans, although computer models that predict
an anterior-to-posterior gradient of formaldehyde deposition in the
upper respiratory tract would predict that formaldehyde would cause
cancer in the nose as well as the nasopharynx in humans.

On the other hand, the lack of information on possible mechanisms by
which formaldehyde might increase the risk of leukemia in humans
tempered the interpretation of the epidemiologic data on that cancer
type.

The entire working group discussed at length this divergence between
the epidemiologic and mechanistic conclusions for leukemia.

Information to support a biologically plausible mechanism could have
supported a stronger conclusion about the evidence of leukemia in
humans.

In the evaluations of the glycol ethers, the working group grappled
with questions of interpretation and scientific judgment.

A recurring issue was the criterion for characterizing a rare tumor or
an unusual set of observations that can carry greater weight than a
typical bioassay result.

A related matter was how to bring in additional information to resolve
difficult questions -- or example, how to consider the results of
historical controls or alternative statistical tests.

When the working group tried to, but could not, reach consensus on a
question of interpretation or scientific judgment, the evaluation
presented the differing positions favored by its members.

For instance, dose-related induction of hepatoblastoma in male and
female mice, considering hepatoblastoma as a rare neoplasm with low
spontaneous incidence in mice, especially in females.

Most of the working group, nevertheless, considered the evidence to be
limited, based on the interpretation of hepatoblastoma being a variant
of hepatocellular carcinoma.

It is important to note that the evaluation of an agent as not
classifiable as to its carcinogenicity to humans is not a
determination of safety, with respect to both cancer and effects other
than cancer.

It indicates that the data did not meet the minimum standards
developed by the IARC for sufficient evidence in experimental animals
and suggests that further testing is needed, particularly when there
is widespread human exposure or another reason for public health
concern.

References

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Last Updated: August 5, 2005

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 A complete list of the evaluations of the IARC
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Lancet Oncol. 2007 Apr; 8(4): 292-3.
    Carcinogenicity of alcoholic beverages.

        * Baan R,
        * Straif K,
        * Grosse Y,
        * Secretan B,
        * El Ghissassi F,
        * Bouvard V,
        * Altieri A,
        * Cogliano V;
        * WHO International Agency for Research on Cancer Monograph
Working Group.

    PMID: 17431955


[ Their Monograph #96 on alcohol references Morando Soffritti:

" 18 Soffritti M, Belpoggi F, Cevolani D, et al. Results
of long-term experimental studies on the
carcinogenicity of methyl alcohol and ethyl
alcohol in rats. Ann N Y Acad Sci 2002; 982: 46-69. " ]

http://genomics.unc.edu/news_events/96_Baan_alcohol.pdf

page 292  http://oncology.thelancet.com Vol 8 April 2007
Policy Watch

Carcinogenicity of alcoholic beverages   http://monographs.iarc.fr/

Robert Baan,
Kurt Straif,
Yann Grosse,
Béatrice Secretan,
Fatiha El Ghissassi,
Véronique Bouvard,
Andrea Altieri,
Vincent Cogliano,
on behalf of the WHO International Agency for Research on Cancer
Monograph Working Group

In February, 2007, 26 scientists from 15 countries met at the
International
Agency for Research on Cancer (IARC) in Lyon, France, to reassess the
carcinogenicity
of alcoholic beverages and of ethyl carbamate (urethane), a frequent
contaminant of fermented foods and beverages.

These assessments will be published as volume 96 of the IARC
Monographs.1

This paper reports on the assessment of alcoholic beverages.

Details on the assessment of ethyl carbamate can be found at
http://monographs.iarc.fr/

Although moderate alcohol consumption has some health benefits,2
the WHO identified the consumption of alcohol as one of the top-10
risks
for worldwide burden of disease.3

In 2002, more than 1.9 billion adults (over 15 years of age) around
the
world were estimated to be regular consumers of alcoholic beverages,
with an average daily consumption of 13 g of ethanol (about one drink).
4

In general, men drink alcohol more often and in larger quantities than
women.

On the basis of production data, per-capita consumption
is highest in eastern Europe and the Russian Federation.

In Africa, South America, and Asia, alcohol consumption is
comparatively lower,
but a large proportion of alcohol is produced locally and remains
unrecorded.

Over the past 40 years, alcohol consumption has remained stable in
most regions of
the world, except in the western Pacific region -- predominantly China
--
where it has increased by about five times.

In addition to ethanol and water, alcoholic beverages can contain many
different substances derived from fermentation,
contamination, and from the use of additives or flavours.

The Working Group reviewed the epidemiological published work on the
possible association between alcohol consumption and cancer at 27
anatomical
sites.

Many studies of different design and in different populations
around the world have consistently shown that regular alcohol
consumption
is associated with an increased risk for cancers
of the oral cavity, pharynx, larynx, and oesophagus.5-7

Daily consumption of around 50 g of alcohol increases the risk for
these cancers by
two to three times, compared with the risk in non-drinkers.

Additionally, the effects of drinking and smoking seem to be
multiplicative.

Furthermore, in populations that are deficient in the activity of
aldehyde dehydrogenase,
an enzyme involved in the catabolism of ethanol,
much higher risks for oesophageal cancer after alcohol consumption
have
been reported than in populations with a fully active enzyme.8

A large number of cohort and case-control studies provide strong
evidence
that the consumption of alcohol is an independent risk factor
for primary liver cancer.

Cirrhosis and other liver diseases often occur before the cancer
becomes manifest
and patients with these disorders generally reduce their alcohol
intake.

Therefore, the effect of alcohol consumption on the risk for liver
cancer is difficult to quantify.9

More than 100 epidemiological studies that assessed the association
between alcohol consumption and breast cancer in women consistently
found an increased risk with increasing alcohol intake.

A pooled analysis of 53 studies on more than 58,000 women with breast
cancer
showed that daily consumption of about 50 g of alcohol is associated
with a relative risk of about 1.5 (95% confidence interval 1.3 --
1.6),
compared with that in non-drinkers.10

For regular consumption of even 18 g of alcohol per day the relative
risk is
significantly increased.10

The association between alcohol consumption and colorectal cancer
has been reported on by more than 50 prospective and case-control
studies.

Pooled results from eight cohort studies11 and data from recent meta-
analyses
provide evidence for an increased relative risk of about 1.4
for colorectal cancer with regular consumption of about 50 g of
alcohol per day,
compared with that in nondrinkers.

This association seems to be similar for colon cancer and for rectal
cancer.11,12

By contrast, both cohort and case-control studies provide consistent
evidence
of no increase in risk for renal-cell cancer with increasing alcohol
consumption.

In several studies, increasing alcohol intake was associated
with a significantly lower risk for renal-cell cancer.

This inverse trend was seen in both men and women.13,14

Furthermore, two prospective cohort studies and several large case-
control studies
showed an inverse association or no association between alcohol
consumption
and non-Hodgkin lymphoma;
most studies showed a lower risk in drinkers than in non-drinkers.
15,16

For cancers of the lung and stomach, there were suggestions that
alcohol
consumption might be associated with an increased risk,
but confounding by smoking and dietary habits could not be ruled out.

For other cancers, the evidence of an association between alcohol
consumption
and cancer risk was generally sparse or inconsistent.

In animals, administration of ethanol in drinking-water caused a dose
related
increase in the incidence of hepatocellular adenomas and carcinomas
in male mice,17 an increased incidence of head and neck carcinomas
in male and female rats, an increased incidence of fore-stomach
carcinomas,
testicular interstitial-cell adenomas, and osteosarcomas
of the head, neck, and other sites in male rats,18
and of

Policy Watch  http://oncology.thelancet.com Vol 8 April 2007 page 293

mammary adenocarcinomas in female rats.19

In most of the studies in which ethanol was co-administered with
known carcinogens, it enhanced the carcinogenic effect.

The Working Group concluded that there is "sufficient evidence" for
the carcinogenicity of
ethanol in animals.20

The major alcohol-metabolising enzymes in humans are the
alcohol dehydrogenases (ADH) that oxidise alcohol (ethanol) to
acetaldehyde,
and the aldehyde dehydrogenases (ALDH) that detoxify acetaldehyde to
acetate.

The variant allele ALDH2*2, which encodes an inactive subunit of the
enzyme ALDH2,
is dominant and highly prevalent in certain populations of Asian
ethnicity (28-45%),
but rare in other ethnic groups.21

Most homozygous carriers of this allele (ALDH2*2/*2) are abstainers or
infrequent drinkers,
because the enzyme deficiency would cause a strong facial flushing
response,
physical discomfort, and severe toxic reactions.

In heterozygous carriers (ALDH2*1/*2, with about 10% residual ALDH2
activity)
these acute adverse effects are less severe, but when alcohol is
consumed
these carriers are at high risk for several alcohol-related
aerodigestive cancers.

For example, genetic epidemiological studies provide strong evidence
that the heterozygous genotype contributes substantially to the
development
of oesophageal cancer related to alcohol consumption,
with relative risks -- compared with carriers of the homozygous
ALDH2*1/*1
genotype, which encodes the active enzyme -- of up to 12 for heavy
drinkers.22

Compared with those with the ALDH2*1/*1 genotype,
the heterozygous carriers have higher levels of acetaldehyde in blood
and saliva
after alcohol drinking, and in a recent study higher levels of
acetaldehyde-related
DNA adducts have been measured in their lymphocytes.23

Overall, the Working Group confirmed that alcoholic beverages are
"carcinogenic to humans" (Group 1),20
and concluded that the occurrence of malignant tumours of the oral
cavity,
pharynx, larynx, oesophagus, liver, colorectum, and female breast
is causally related to alcohol consumption.

For renal-cell cancer and non-Hodgkin lymphoma
the Working Group concluded that there is "evidence suggesting lack of
carcinogenicity"
for alcohol drinking.20

The addition of breast cancer and colorectal cancer,
two of the most common cancers worldwide, to the list of cancers
causally related to alcohol consumption suggests that the proportion
of cancers
attributable to alcohol consumption is higher than previously
estimated.

Because these associations were generally noted with different types
of alcoholic beverage, and in view of the carcinogenicity of ethanol
in animals,
the Working Group also classified ethanol in alcoholic beverages
as "carcinogenic to humans" (Group 1).20

The Working Group agreed that the substantial mechanistic evidence
in humans deficient in aldehyde dehydrogenase indicates that
acetaldehyde
derived from the metabolism of ethanol in alcoholic beverages
contributes to causing malignant oesophageal tumours.

The IARC authors declared no conflicts of interest.

1 IARC. IARC monographs on the evaluation of carcinogenic risks to
humans. Volume 96.
Alcoholic beverage consumption and ethylcarbamate (urethane).
Lyon: International Agency for Research on Cancer (in press).

2 WHO. WHO Global Status Report on Alcohol
2004. Geneva: World Health Organization,
Department of Mental Health and Substance Abuse.

3 Ezzati M, Rodgers A, Lopez AD, et al. Mortality
and burden of disease attributable to
individual risk factors. In: Ezzati M, Lopez AD,
Rodgers A, Murray CJL, eds. Comparative
quantifi cation of health risks. Global and
regional burden of disease attributable to
selected major risk factors. Volume 2. Geneva:
World Health Organization, 2004: 2141-66.

4 WHO. WHO Global Alcohol Database.
http://www.who.int/globalatlas/default.asp
(accessed March 2, 2007).

5 Boeing H. Alcohol and risk of cancer of the upper
gastrointestinal tract: first analysis of the EPIC
data. In: Riboli E, Lambert R, eds. Nutrition and
lifestyle: opportunities for cancer prevention.
IARC Sci Publ 156. Lyon: International Agency
for Research on Cancer, 2002: 151-54.

6 Talamini R, Bosetti C, La Vecchia C, et al.
Combined eff ect of tobacco and alcohol on
laryngeal cancer risk: a case-control study.
Cancer Causes Control 2002; 13: 957-64.

7 Znaor A, Brennan P, Gajalakshmi V, et al.
Independent and combined eff ects of tobacco
smoking, chewing and alcohol drinking on the
risk of oral, pharyngeal and esophageal cancers
in Indian men. Int J Cancer 2003; 105: 681-86.

8 Yokoyama A, Omori T. Genetic polymorphisms
of alcohol and aldehyde dehydrogenases and
risk for esophageal and head and neck cancers.
Alcohol 2005; 35: 175-85.

9 Bagnardi V, Blangiardo M, La Vecchia C, et al.
A meta-analysis of alcohol drinking and cancer
risk. Br J Cancer 2001; 85: 1700-05.

10 Hamajima N, Hirose K, Tajima K, et al. Alcohol,
tobacco and breast cancer - collaborative
reanalysis of individual data from 53
epidemiological studies, including 58,515 women
with breast cancer and 95,067 women without
the disease. Br J Cancer 2002; 87: 1234-45.

11 Cho E, Smith-Warner SA, Ritz J, et al. Alcohol
intake and colorectal cancer: a pooled analysis
of 8 cohort studies. Ann Intern Med 2004;
140: 603-13.

12 Moskal A, Norat T, Ferrari P, Riboli E. Alcohol
intake and colorectal cancer risk: a dose response
meta-analysis of published cohort
studies. Int J Cancer 2007; 120: 664-71.

13 Hu J, Mao Y, White K. Diet and vitamin or
mineral supplements and risk of renal cell
carcinoma in Canada. Cancer Causes Control
2003; 14: 705-14.

14 Hsu CC, Chow WH, Boff etta P, et al. Dietary risk
factors of kidney cancer in eastern and central
Europe. Am J Epidemiol 2007 (in press).

15 Morton LM, Zheng T, Holford TR, et al.
Alcohol consumption and risk of non-Hodgkin
lymphoma: a pooled analysis. Lancet Oncol
2005; 6: 469-76.

16 Besson H, Brennan P, Becker N, et al. Tobacco
smoking, alcohol drinking and non-Hodgkin's
lymphoma: a European multicenter casecontrol
study (Epilymph). Int J Cancer 2006; 119: 901-08.

17 US National Toxicology Program. Toxicology
and Carcinogenesis Studies of Urethane +
Ethanol (CAS Nos. 51-79-6 & 64-17-5) in
F344/N Rats and B6C3F1 Mice (drinking-water
studies). NTP Technical Report No. 510.
Bethesda: National Institutes of Health, 2004.

18 Soffritti M, Belpoggi F, Cevolani D, et al. Results
of long-term experimental studies on the
carcinogenicity of methyl alcohol and ethyl
alcohol in rats. Ann N Y Acad Sci 2002; 982: 46-69.

19 Watabiki T, Okii Y, Tokiyasu T, et al. Long-term
ethanol consumption in ICR mice causes
mammary tumor in females and liver fibrosis
in males. Alcohol Clin Exp Res 2000; 24: 117S-22S.

20 IARC. Preamble to the IARC monographs on
the evaluation of carcinogenic risks to humans.
http://monographs.iarc.fr/ENG/Preamble/
CurrentPreamble.pdf (accessed March 2, 2007).

21 Goedde HW, Agarwal DP, Fritze G, et al.
Distribution of ADH2 and ALDH2 genotypes in
diff erent populations. Hum Genet 1992; 88: 344-46.

22 Lewis SJ, Smith GD. Alcohol, ALDH2, and
esophageal cancer: a meta-analysis which
illustrates the potentials and limitations of a
Mendelian randomization approach. Cancer
Epidemiol Biomarkers Prev 2005; 14: 1967-71.

23 Matsuda T, Yabushita H, Kanaly RA, et al.
Increased DNA damage in ALDH2-deficient
alcoholics. Chem Res Toxicol 2006; 19: 1374-78.

Monograph Working Group Members

WC Willett -- Chair (USA);  WWillett from hsph.harvard.edu,
AB Miller,  ab.miller from sympatico.ca,
J Rehm (Canada);  jtrehm from aol.com,  Centre for Addiction and Mental
Health, Toronto, Ontario Canada
L Cai (China);  l0cai001 from louisville.edu,  Dr. Lu Cai, Department of
Medicine, University of Louisville School of Medicine, 511 South Floyd
St., MDR 533, Louisville, KY 40202  l0cai001 from louisville.edu
 Department of Medicine, University of Louisville, School of Medicine,
Louisville, Kentucky
 Department of Pharmacology and Toxicology, University of Louisville,
School of Medicine, Louisville, Kentucky
K Bloomfield (Denmark);  Kim Bloomfield  kbl from health.sdu.dk, Unit of
Health Promotion Research, University of Southern Denmark, Niels Bohrs
Vej 9, 6700 Esbjerg, Denmark. Tel: +45-6550 4111; Fax: +45-6550 4283
P Eriksson (Finland);  per.eriksson from ebc.uu.se,  Department of
Environmental Toxicology, Uppsala University, Norbyvagen 18A, S-752 36
Uppsala, Sweden
J Bénichou (France, unable to attend);  jacques.benichou from chu-rouen.fr,
University of Rouen School of Medicine and Rouen University Hospital,
Department of Biostatistics, Rouen, France
DW Lachenmeier,  Lachenmeier from web.de,  Chemisches und
Veterinaruntersuchungsamt (CVUA) Karlsruhe, Weissenburger Str. 3,
D-76187, Karlsruhe, Germany,  Institut fur Rechtsmedizin, Technische
Universitat Dresden, Fetscherstr. 74, D-01307 Dresden, Germany
HK Seitz (Germany);  helmut_karl.seitz from urz.uni-heidelberg.de,
Laboratory of Alcohol Research, Liver Disease and Nutrition and
Department of Medicine, Salem Medical Center, Heidelberg, Germany
C La Vecchia (Italy);
S Kono,  skono from phealth.med.kyushu-u.ac.jp,  Department of Preventive
Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka,
Japan
A Yokoyama (Japan);    National Hospital Organization Kurihama
Alcoholism Center, Kanagawa, Japan
S-I Cho (Republic of Korea);    Department of Environmental Health,
School of Public Health, Seoul National University, 28 YeonKeon-Dong,
Jongro-Gu, Seoul 110-799, Republic of Korea.
Sung-il Cho, MD;   Department of Environmental Health, Harvard School
of Public Health, 665 Huntington Avenue, FXB-101, Boston, MA
02115-6096
Sung-il Cho,  scho from snu.ac.kr, Department of Epidemiology, School of
Public Health and Institute of Health and Environment, Seoul National
University, Jongno-gu Yeongun-dong 28, Seoul 110-460, Republic of
Korea
L-L Griciute (Lithuania);
E Weiderpass (Norway);   ewv from kreftregisteret.no, Department of
Etiological Research, The Cancer Registry of Norway, N-0310 Oslo,
Norway
M Marques (Portugal);
N Rehn-Mendoza (Singapore);
G Gmel (Switzerland);   gerhard.gmel from chuv.ch,  Alcohol Treatment
Center, Lausanne University Hospital, CH-1011 Lausanne, Switzerland
NE Allen,  naomi.allen from cancer.org.uk,  Cancer Research UK Epidemiology
Unit, University of Oxford, Radcliffe Infirmary, Oxford OX2 6HE, UK
V Beral (UK);   beralv from icrf.icnet.uk,  Cancer Research UK Epidemiology
Unit, University of Oxford, Radcliffe Infirmary, Oxford OX2 6HE, UK
LM Anderson,  Andersol from mail.ncifcrf.gov,  Laboratory of Comparative
Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD
21702, USA
FA Beland,   fbeland from nctr.fda.gov,  Division of Biochemical
Toxicology, National Center for Toxicological Research, Jefferson,
Arkansas 72079, USA
PJ Brooks,  pjbrooks from mail.nih.gov,  Section on Molecular Neurobiology,
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and
Alcoholism, 5625 Fishers Lane, Room 3S32, MSC 9412, Rockville, MD
20852, USA
DW Crabb,  dcrabb from iupui.edu,  Indiana Alcohol Research Center,
Division of Gastroenterology and Hepatology, Department of Medicine,
Indiana University School of Medicine, Indianapolis, USA
SM Gapstur,   sgapstur from northwestern.edu,  Department of Preventive
Medicine, Feinberg School of Medicine, Northwestern University,
Chicago, IL 60611, USA
I Rusyn,  iir from unc.edu,    Department of Environmental Sciences and
Engineering, University of North Carolina at Chapel Hill, Chapel Hill,
NC 27599, USA
Z-F Zhang (USA)    ZFZHANG from UCLA.EDU,  ZUO-FENG ZHANG
Department of Epidemiology, UCLA School of Public Health, 71-225 CHS,
Box 951772, 650 Charles E. Young Drive, South Los Angeles, CA
90095-1772  (310) 825-8418 (Office) (310) 206-6039 (Fax)

Conflicts of interests
DWC is a member of the Medical Advisory Council of the Alcoholic
Beverages Medical Research Foundation.  www.abmrf.org/
1122 Kenilworth Drive, Suite 407, Baltimore, Maryland 21204
410.821.7066  Fax: 410.821.7065  info from abmrf.org,

All other members of the Working Group declared no conflicts of
interests.

Invited Specialists  None

Representatives  A Huici-Montagud (European Commission, Luxembourg)

Observers  None
///////////////////////////////////////////////////////////


 BMC Gastroenterol. 2006 Dec  4;6: 41.
    Time trends in socioeconomic differences in incidence rates of
cancers of gastro-intestinal tract in Finland.

        * Weiderpass E,
        * Pukkala E.

    Department of Etiological Research, The Cancer Registry of Norway,
N-0310 Oslo, Norway. ewv from kreftregisteret.no,

    BACKGROUND: The magnitude of socioeconomic differences in health
varies between societies, and over time within a given society.
We studied the association between social class and incidence of
cancers of the gastro-intestinal tract over time in a large cohort in
Finland.
METHODS: We studied social class variation among 45-69 year-old Finns
during 1971-95 in incidence of cancers of the gastro-intestinal tract
by means of a computerized record linkage of the Finnish Cancer
Registry and the 1970 Population Census, which included social class
data.
RESULTS: There were 2.3 million individuals in the cohort under follow-
up, with 1622 cases of cancer of the esophagus, 8069 stomach (non-
cardia), 1116 cardia, 408 small intestine, 6361 colon, 5274 rectum,
1616 liver, 1756 gallbladder, and 5084 pancreas during 1971-1995.
Cancers of the esophagus, stomach, cardia, gallbladder and pancreas
were most common among persons belonging to a low social class.
Cancers of the small intestine in males only, colon in both genders,
and rectum in females were most common in the higher social classes.
Incidence of stomach cancer decreased and incidence of colon cancer
increased over time in both genders in all social classes, and the
large differences between social classes remained unchanged over time.
Incidence rates of cardia cancer did not change substantially over
time.
CONCLUSION: There is a large variation in incidence of cancer of the
gastrointestinal tract by social class in Finland.

Although much of the observed social class differences probably could
be explained by known etiological factors such as diet, physical
exercise, alcohol consumption, smoking and exogenous hormone use,
part of the variation is apparently attributable to largely unknown
factors.
PMID: 17144908


Int J Cancer. 2004 Feb 20; 108(5): 741-9.
    The role of type of tobacco and type of alcoholic beverage in oral
carcinogenesis.

        * Castellsague X,
        * Quintana MJ,
        * Martinez MC,
        * Nieto A,
        * Sanchez MJ,
        * Juan A,
        * Monner A,
        * Carrera M,
        * Agudo A,
        * Quer M,
        * Munoz N,
        * Herrero R,
        * Franceschi S,
        * Bosch FX.

    Institut Catala d'Oncologia, Servei d'Epidemiologia i Registre del
Cancer, L'Hospitalet de Llobregat, Barcelona, Spain.
xcastellsague from ico.scs.es,

    Incidence rates of oral and oropharyngeal cancers (oral cancer) in
Spain are among the highest in Europe.
Spain has a population heavily exposed to various types of tobacco and
alcoholic beverages but the role and impact of tobacco type and
beverage type in oral carcinogenesis remain controversial.
To estimate the independent and joint effects of tobacco smoking and
alcohol drinking habits on the risk of developing oral cancer, we
carried out a multicenter, hospital-based, case-control study in
Spain. Data from 375 patients newly diagnosed with cancer of the oral
cavity or oropharynx and 375 matched control subjects were analyzed
using multivariate logistic regression procedures.
All exposure characteristics of amount, duration and cessation of both
tobacco smoking and alcohol drinking were strongly associated with
cancer risk following a dose-dependent relationship.
At equal intake or duration levels, black-tobacco smoking and drinking
of spirits were both associated with a 2- to 4-fold increase in cancer
risk compared to blond tobacco smoking or drinking of wine or beer,
respectively.
While ever exposure to smoking only or drinking only was associated
with a moderate and nonsignificant increase in cancer risk, a history
of simultaneous exposure to both habits was associated with a 13-fold
increase that was compatible with a synergistic effect model (p-value
for interaction: 0.008).
Exposure to black tobacco smoking and/or drinking of spirits may
account for up to 77% of oral cancer occurrence in Spain.
Both black tobacco smoking and drinking of spirits place individuals
at a very high risk of developing oral cancer.

Simultaneous exposure to tobacco and alcohol consumption increases
oral cancer risk in a synergistic fashion, even when consumption
levels are moderate.

These results underline the importance of type of tobacco and alcohol
concentration in oral carcinogenesis.
Copyright 2003 Wiley-Liss, Inc.  PMID: 14696101


http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=2817164
free full text pdf

Am J Public Health. 1989 Nov; 79(11): 1516-20.
    Carcinogenicity of dark liquor.

        * Rothman KJ,
        * Cann CI,
        * Fried MP.
Department of Medicine, Boston University Medical Center, MA.
KENNETH J. ROTHMAN, DRPH,  krothman from rti.org,   Epidemiology Research,
RTI Health Solutions, RTI International, Research Triangle Park, North
Carolina, USA
CRISTINA I. CANN,    Former Associate Editor, Epidemiology; Boston
University School of Public Health
MARVIN P. FRIED, MD  mfried from montefiore.org,  Montefiore Medical
Center, Medical Arts Pavilion, 3400 Bainbridge Avenue, MAP, Room 3rd
floor, Bronx, NY 10467  (718) 920-2991  Fax: (718) 882-2463
	Professor, Department of Otorhinolaryngology - Head & Neck Surgery
	Chair, Department of Otorhinolaryngology - Head & Neck Surgery


    To investigate whether the non-alcohol content of distilled
alcoholic beverages affects the carcinogenicity of the beverage, we
conducted an epidemiologic study of laryngeal and hypopharyngeal
cancer.
We interviewed 384 cases (or spouses, for deceased cases), and
compared their responses with those of 876 controls.
We classed distilled liquors as dark or light, a rough division
according to content of potentially carcinogenic compounds in the
beverages.
The relative effect on hypopharyngeal cancer risk was much stronger
for those who reported high consumption of dark liquor (relative risk
= 4.4, 90% confidence interval = 2.9, 6.8) than for those reporting
comparable consumption of light liquor (relative risk = 1.3, 90% CI =
0.8, 2.1).
For laryngeal cancer, consumption of dark liquor had a smaller effect,
and there was little distinction between the effects of dark and light
liquor.
The data appear consistent with the theory that the non-alcoholic
content of distilled alcoholic beverages is a determinant of cancer
risk, and that alcoholic beverages act topically rather than
systemically in their carcinogenic action.

    PMID: 2817164


J Agric Food Chem. 2006 May 31; 54(11): 3911-5.
    Quantification of selected volatile constituents and anions in
Mexican Agave spirits (Tequila, Mezcal, Sotol, Bacanora).

        * Lachenmeier DW,
        * Sohnius EM,
        * Attig R,
        * Lopez MG.

    Chemisches und Veterinaruntersuchungsamt (CVUA) Karlsruhe,
Weissenburger Strasse 3, 76187 Karlsruhe, Germany   Lachenmeier from web.de

    A large collection (n = 95) of Mexican Agave spirits with
protected appellations of origin (Tequila, Mezcal, Sotol, and
Bacanora) was analyzed using ion and gas chromatography
Because of their production from oxalate-containing plant material,
all Agave spirits contained significant concentrations of oxalate
(0.1-9.7 mg/L).
The two Tequila categories ("100% Agave" and "mixed") showed
differences in the methanol, 2-/3-methyl-1-butanol, and 2-
phenylethanol concentrations with lower concentrations in the mixed
category.
Mezcal showed no significant differences in any of the evaluated
parameters that would allow a classification.
Sotol showed higher nitrate concentrations and lower 2-/3-methyl-1-
butanol concentrations.
Bacanora was characterized by exceptionally high acetaldehyde
concentrations and a relatively low ethyl lactate content.

The methanol content was the most problematic compound regarding the
Mexican standards:
two Tequilas (4%), five Sotols (31%), and six Bacanoras (46%) had
levels above the maximum methanol content of 300 g/hL of alcohol.

In conclusion, the composition of Mexican Agave spirits was found to
vary over a relatively large range.
PMID: 16719514


J Agric Food Chem. 2005 Mar 23; 53(6): 2151-7.
    Multivariate analysis of FTIR and ion chromatographic data for the
quality control of tequila.

        * Lachenmeier DW,
        * Richling E,
        * Lopez MG,
        * Frank W,
        * Schreier P.

    Chemisches und Veterinaruntersuchungsamt (CVUA) Karlsruhe,
Weissenburger Strasse 3, 76187 Karlsruhe, Germany. Lachenmeier from web.de,

    Principal component analysis (PCA) was applied to the
chromatographic and spectroscopic data of authentic Mexican tequilas
(n = 14) and commercially available samples purchased in Mexico and
Germany (n = 24).
The scores scatter plot of the first two principal components (PC) of
the anions chloride, nitrate, sulfate, acetate, and oxalate accounting
for 78% of the variability allowed a classification between tequilas
bottled in Mexico and overseas;
however, no discrimination between tequila categories was possible.
Mexican products had a significantly (p = 0.0014) lower inorganic
anion concentration (range = 1.5-5.1 mg/L; mean = 2.5 mg/L) than the
products bottled in the importing countries (range = 3.3-62.6 mg/L;
mean = 26.3 mg/L).
FTIR allowed a rapid screening of density and ethanol as well as the
volatile compounds methanol, ethyl acetate, propanol-1, isobutanol,
and 2-/3-methyl-1-butanol using partial least-squares regression
(precisions = 5.3-29.3%).
Using PCA of the volatile compounds, a differentiation between tequila
derived from "100% agave" (Agave tequilana Weber var. azul, Agavaceae)
and tequila produced with other fermentable sugars ("mixed"tequila)
was possible.
The first two PCs describe 89% of the total variability of the data.
Methanol and isobutanol influenced the variability in PC1, which led
to discrimination.

The concentrations of methanol and isobutanol were significantly
higher (methanol, p = 0.004; isobutanol, p = 0.005) in the 100% agave
(methanol, 297.9 ± 49.5; isobutanol, 251.3 ± 34.9) than in the mixed
tequilas (methanol, 197.8 ± 118.5; isobutanol, 151.4 ± 52.8).
PMID: 15769149


Int J Cancer. 1979 Apr 15; 23(4): 443-7.
    Oesophageal cancer and alcohol consumption; importance of type of
beverage.

        * Tuyns AJ,
        * Pequignot G,
        * Abbatucci JS.

    The role of alcohol consumption in oesophageal cancer in Normandy
has been studied by a retrospective study of 312 male cases and 869
controls.
The linear relationship between the logarithm of risk and overall
daily alcohol consumption was confirmed after adjustment for tobacco.
The role of each specific alcoholic beverage was further investigated
by computing relative risks for individuals consuming a given beverage
and for those drinking other beverages only, within each overall
alcohol consumption category.
It is concluded:
(1) that there is a linear relationship between the logarithm of risk
of oesophageal cancer and overall daily ethanol consumption, whatever
the beverage
(2) that the effect is more marked for strong beverages
(3) that there is an additional risk related to apple brandy and
cider.
PMID: 437923
///////////////////////////////////////////////////////////


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 2007.04.24
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

http://www.ramazzini.it./fondazione/pdfUpload/Ann%20NY%20Acad%20Sci%20982%2087-105_2002.pdf
19 page free full text pdf

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 from 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 from ramazzini.it

http://www.ramazzini.it./fondazione/pdfUpload/Ann%20NY%20Acad%20Sci%20982%2046-69_2002.pdf
24 page free full text pdf

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/press_release/1472_en.html

http://www.efsa.eu.int/science/afc/afc_opinions/1471_en.html

http://www.efsa.eu.int/press_room/media_events/catindex_en.html

http://www.flyonthewall.com/FlyBroadcast/efsa.eu.int/AspartamePressConference/

www.efsa.eu.int/science/afc/afc_opinions/1471/afc_op_ej356_aspartame_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
///////////////////////////////////////////////////////////


aspartame (methanol, formaldehyde) toxicity research summary: Rich
Murray 2007.04.30
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:
www.epa.gov/teach/chem_summ/Formaldehyde_summary.pdf
2007.01.05 [ does not discuss formaldehyde from methanol
or aspartame ]
http://www.epa.gov/teach/teachsurvey.html comments
teach from 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 from comcast.net
505-501-2298 1943 Otowi Road, Santa Fe, New Mexico 87505

http://groups.yahoo.com/group/aspartameNM/messages
group with 74 members, 1,419 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

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

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

This pathway contributes to a long-term unobserved compartment.

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

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

>From the data of Dorman et al. [1994] and Medinsky et al. [1997],
it can further be calculated that 48 h following the start
of a 2-h inhalation exposure to 900 ppm of 14C-methanol vapors
in female cynomolgus monkeys,
only 23% of the absorbed 14C-methanol was eliminated from the body.

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

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

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

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

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

http://groups.yahoo.com/group/aspartameNM/message/1406
brain cell tangles and neuron death similar to Alzheimers
via low dose formaldehyde from methanol,
Chunlai Nie, Rongqiao He et al, China, 2007.01.23 BMC
Neuroscience 28 pages, 63 references: Murray 2007.01.24


http://groups.yahoo.com/group/aspartameNM/message/1385
Coca-Cola carcinogenicity in rats, Ramazzini Foundation,
F Belpoggi, M Soffritti, Annals NY Academy Sciences
2006 Sept, parts of 17 pages: Murray 2006.12.02

http://groups.yahoo.com/group/aspartameNM/message/1382
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


http://groups.yahoo.com/group/aspartameNM/message/1369
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

http://groups.yahoo.com/group/aspartameNM/message/1341
Connecticut bans artificial sweeteners in schools,
Nancy Barnes, New Milford Times: Murray 2006.05.25


http://groups.yahoo.com/group/aspartameNM/message/1376
soft drinks and adolescent hyperactivity, mental distress,
conduct problems, Lars Lien, Nanna Lien, Sonja Heyerdahl,
Mayne Thoresen, Espen Bjertness 2006 Oct., A J Pub Health:
Murray 2006.10.21

http://groups.yahoo.com/group/aspartameNM/message/1375
healthy diet, vitamins, and fish oil help reduce
depression and violence, studies by Joseph Hibbeln,
Bernard Gesch, and Stephen Schoenthaler, articles by
Felicity Lawrence in UK Guardian Unlimited and Pat
Thomas in The Ecologist: Murray 2006.10.21

http://groups.yahoo.com/group/aspartameNM/message/1353
carcinogenic effect of inhaled formaldehyde, Federal
Institute of Risk Assessment, Germany -- same safe level
as for Canada: Murray 2006.06.02

http://groups.yahoo.com/group/aspartameNM/message/1352
Home sickness -- indoor air often worse, as our homes
seal in pollutants [one is formaldehyde, also from the 11%
methanol part of aspartame],
Megan Gillis, WinnipegSun.com: Murray 2006.06.01


http://groups.yahoo.com/group/aspartameNM/message/1414
effect of aspartame on oncogene and suppressor gene expressions in
mice, Katalin Gambos, Istvan Ember, et al, University of Pecs,
Hungary, In Vivo 2007 Jan; scores of their relevant past studies since
1977: Murray 2007.04.14

http://groups.yahoo.com/group/aspartameNM/message/1366
toxicity in rat brains from aspartame, Vences-Mejia A,
Espinosa-Aguirre JJ et al 2006 Aug: Murray 2006.09.06

http://groups.yahoo.com/group/aspartameNM/message/1373
aspartame rat brain toxicity re cytochrome P450 enzymes,
especially 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

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

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/1349
NIH NLM ToxNet HSDB Hazardous Substances Data Bank
inadequate re aspartame (methanol, formaldehyde,
formic acid): Murray 2006.08.19

http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~HwoSfJ:1
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


http://groups.yahoo.com/group/aspartameNM/message/1052
DMDC: Dimethyl dicarbonate 200mg/L in drinks adds methanol
98 mg/L ( becomes formaldehyde in body ): EU Scientific
Committee on Foods 2001.07.12: Murray 2004.01.22


http://www.HolisticMed.com/aspartame mgold from holisticmed.com
Aspartame Toxicity Information Center Mark D. Gold
12 East Side Drive #2-18 Concord, NH 03301 603-225-2100

http://www.holisticmed.com/aspartame/abuse/methanol.html
"Scientific Abuse in Aspartame Research"

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/scf2002-response.htm
Mark Gold exhaustively critiques European Commission
Scientific Committee on Food re aspartame ( 2002.12.04 ):
59 pages, 230 references
///////////////////////////////////////////////////////////


http://groups.yahoo.com/group/aspartameNM/message/782
RTM: Smith, Terpening, Schmidt, Gums:
full text: aspartame, MSG, fibromyalgia 2002.01.17
Jerry D Smith, Chris M Terpening,
Siegfried OF Schmidt, and John G Gums
Relief of Fibromyalgia Symptoms Following
Discontinuation of Dietary Excitotoxins.
The Annals of Pharmacotherapy 2001; 35(6): 702-706.
Malcolm Randall Veterans Affairs Medical Center,
Gainesville, FL, USA.
BACKGROUND: Fibromyalgia is a common rheumatologic
disorder that is often difficult to treat effectively.
CASE SUMMARY: Four patients diagnosed with fibromyalgia
syndrome for two to 17 years are described.
All had undergone multiple treatment modalities with
limited success.
All had complete, or nearly complete,
resolution of their symptoms within months after
eliminating monosodium glutamate (MSG)
or MSG plus aspartame from their diet.
All patients were women with multiple comorbidities
prior to elimination of MSG.
All have had recurrence of symptoms whenever MSG
is ingested.

Siegfried O. Schmidt, MD Asst. Clinical Prof.
siggy from shands.ufl.edu
Community Health and Family Medicine, U. Florida,
Gainesville, FL Shands Hospital West Oak Clinic
Gainesville, FL 32608-3629 352-376-5071
///////////////////////////////////////////////////////////

http://groups.yahoo.com/group/aspartameNM/message/915
formaldehyde toxicity: Thrasher & Kilburn: Shaham: EPA:
Gold: Wilson: CIIN: Murray 2002.12.12

Thrasher (2001): "The major difference is that the
Japanese demonstrated the incorporation of FA and its
metabolites into the placenta and fetus.
The quantity of radioactivity remaining in maternal and
fetal tissues at 48 hours was 26.9% of the administered
dose." [ Ref. 14-16 ]

Arch Environ Health 2001 Jul-Aug; 56(4): 300-11.
Embryo toxicity and teratogenicity of formaldehyde.
[100 references]
Thrasher JD, Kilburn KH. toxicology from drthrasher.org
Sam-1 Trust, Alto, New Mexico, USA.  full text
http://www.drthrasher.org/formaldehyde_embryo_toxicity.html

http://www.drthrasher.org/formaldehyde_1990.html full text
Jack Dwayne Thrasher, Alan Broughton, Roberta Madison.
Immune activation and autoantibodies in humans with
long-term inhalation exposure to formaldehyde.
Archives of Environmental Health. 1990; 45: 217-223.
PMID: 2400243
///////////////////////////////////////////////////////////




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