Murray: Wilson: CIIN: EPA: Gold: Thrasher & Kilburn: Shaham: formaldehyde toxicity 8.22.2 rmforall
- Murray: Wilson: CIIN: EPA: Gold: Thrasher & Kilburn: Shaham:
formaldehyde toxicity 8.22.2 rmforall
Chemical Injury Information Network
P.O.Box 301 White Sulphur Springs, MT 59645
406.547.2255 fax 2455
Chemical Exposure and Human Health; Cynthia Wilson, covers 314
chemicals in an easy-to read format. $55.00 US plus $2.00 shipping to
McFarland and Company Ltd.; P.O. Box 611; Jefferson NC 28640,
The Human Consequences of the Chemical Problem by Cindy
Duehring and Cynthia Wilson, $7.20, TT Publishing, PO Box T,
White Sulphur Springs MT 59645
Formaldehyde (From "Chemical Exposure and Human Health")
Eye, ear and throat irritation;
Acute sense of smell;
Altered tissue proteins;
Blood in urine;
Burns, nasal and throat;
Cardiac impairment, palpations, and arrhythmias;
Central nervous system depression;
Changes in higher cognitive functions ;
Chest pains and tightness;
Flu-like or cold like illness;
Frequent urination with pain;
Hyperactive airway disease;
Immune system sensitization;
Impaired attention span;
Impaired capacity to focus attention;
Inability or difficulty swallowing;
Inability to recall words and names;
Inconsistent IQ profiles;
Inflammatory diseases of the reproductive organs;
Joint pain, aches and swelling;
Loss of memory;
Loss of sense of smell;
Loss of taste;
Menstrual and testicular pain;
Muscle spasms and cramps;
Nasal congestion, Crusting and mucosa inflammation;
Numbness and tingling of the forearms and finger tips;
Pale, clammy skin;
Partial laryngeal paralysis;
Post nasal drip;
Reduced body temperature;
Retarded speech pattern;
Ringing or tingling in the ear;
Sensitivity to sound;
Short term memory loss;
Shortness of breath;
Suspected of causing cancer (see comment from NIOSH).
Metabolized as formic acid. Note: Will cross sensitize to formic acid.
Comparison of ciliostatic effects showed formaldehyde to the most
toxic of the aldehydes. EPA estimates that 15 people in 1 million will
get cancer from lifetime exposure of 1 ppb. Neurotoxin.
Trade Names/synonyms: Quaternium-15; Metanal; Meltyl aldehyde;
Methylene oxide; Formalin; Formic aldehyde; Formalith; Fyde; BVF;
Morbicid; Oxymethylene; Oxomethane; Lysoform; Superlysoform;
NIOSH: Carcinogen at any exposure level;
NIOSH REL: 0.016 ppm (10 hr/day 40 hr. wk);
0.100 ppm (ceiling limit to not exceed 15
OSHA: PEL: 0.750 ppm (8 hr/day-40 hr/wk-PP/S);
2000 ppm (exposure to not exceed 15 min);
NAS: There is no (constant) population
threshold for irritation effects;
NRC: Fewer than 20% but perhaps no more than 10% of
the general population may be suspectable to formaldehyde and may react
acutely at any exposure level;
ACGIH: Suspected human carcinogen;
IDLH: 30 ppm;
Chemical Exposure and Human Health: Page 182;
References: 84,17,18,30,31,129,278,279,285, 88,290,297,299,300,304,
8. Berthold-Bond, A., Clean & Green, Woodstock, NY:
Cress Press, 1990.
14. Chesebrough-Ponds USA Co., product label for Rave All in One hair
17. Concrete Facts, "99.99 Percent?" March 1991, Vol.1 no.1 and/or
Rachel's Hazardous Waste News #207, "Hardardous Waste
Incineration- Part 4; Real Alternatives to Incinerations,"
November 14, 1988.
18. "Congress: HR 1066 Needed to Turn Heat Up on Employers,
Regulators, Congress Told", Indoor Air Pollution News,
Washington, DC: Buraff, August 22, 1991.
30. Lander Co., product label for Rose Scented Skin Cream, ca. 1992.
31. Lander Co., product label for Vitamin E Lotion, ca. 1992.
129. "National Library of Medicine's Toxicology Information Program,
Agency for Toxic Substances and Disease Registry, Hazardous
Substances Data Bank, "Formaldehyde", as of January 11, 1992.
279. National Research Council, Assembly of Life Sciences, Committee
on Aldehydes, Based on Toxicology and Environmental Health
Hazards, Formaldehydes and other Aldehydes, Washington, DC:
National Academy Press, 1981.
285. New Jersey Department of Health, "Hazardous Substance Fact Sheet
288. Proctor and Gamble Co., label for Ivory Free Conditioner, U.S.
290. Redmond Products, product label for Aussie Mega Shampoo with
297. Swanson, J.R., "Formaldehyde: The Psychological and Educational
Implications of Formaldehyde Toxicology," Seattle, WA:
University of Washington, College of Education, 1984.
299. Thomas, C.L., editor, Taber's Cyclopedic Medical Dictionary,
16th Edition, Philadelphia, PA: F.A. Davis Company, 1989.
A History of the Chemical Injury Information Network
PO Box 301, White Sulphur Springs, MT 59645; (406) 547-2255
Founded in 1990, the Chemical Injury Information Network
(CIIN) is a 501(c)3, tax-exempt, non-profit support, advocacy
organization run by the chemically injured primarily for the benefit
of the chemically injured. Its primary focus is on education,
credible research on multiple chemical sensitivity (MCS), and the
empowerment of the chemically injured. CIIN publishes the
monthly newsletter Our Toxic Times and has over 5,000
members in 35 countries.*
CIIN merged with Cindy Duehring's Environmental Access
Research Network (EARN) in 1994. EARN now serves as the
research division of CIIN and is responsible for the administration
of one the largest private libraries on chemical health issues in
existence. Its primary focus is to make scientific, medical, legal,
and government literature available to health care professionals,
expert witnesses, attorneys, and lay persons. EARN publishes
Environmental Access Profiles and the semi-monthly newsletter
Medical & Legal Briefs.
In 1996, CIIN formed a new division to raise money to fund
research into MCS. The MCS Research Fund has a medical
advisory board that peer reviews and prioritizes research
proposals for funding.
Considered one of the leading organizations in the world for
chemical health problems, CIIN/EARN receives hundreds of
requests each month for information on toxic health problems.
They regularly work with health care professionals in Algeria,
Australia, Austria, Canada, Germany, India, Sweden, Venezuela,
United Kingdom, and the United States. They have worked with
universities in Australia, Canada, Germany, Philippines, Mexico,
and the United States. CIIN/EARN have also provided
information not only to the US government, but to the European
Union and the governments of Canada, Costa Rica, Finland, New
Zealand, and Venezuela. CIIN has received recognition for its
work on chemical health issues from the United Nations'
Environmental Programme and from the European Union.
In 1991, CIIN was accepted by the Agency for Toxic
Substances and Disease Registry (ATSDR) as a clearinghouse for
information on the adverse health effects of chemical exposures.
CIIN/EARN have also earned the respect of legislators with over
100 US Senators and Representatives referring their chemically
injured constituents to them. In addition, the National Institutes of
Health, the National Institute for Environmental Health Sciences,
the National Institute for Occupational Safety and Health, the
ATSDR, the Centers for Disease Control and Prevention, and
several divisions of the Environmental Protection Agency refer
people who have been chemically injured to CIIN/EARN.
Cindy Duehring, EARN's director, and Cynthia Wilson, CIIN's
executive director, were commissioned by the Chemical Impact
Project to write a "white paper" in 1994. The 65-page report,
The Human Consequences of the Chemical Problem (available
from TT Publishing, PO Box T, White Sulphur Springs MT
59645 for $7.20), was presented to Vice President Al Gore, First
Lady Hillary Rodham Clinton, Secretary of the National Institutes
of Health Donna Shalala, and the Centers for Disease Control and
Prevention (CDC). The CDC had the paper peer reviewed and it
was found to have "merit". A conference was convened to discuss
the health issues raised by the paper. The ATSDR called it
"powerful and well researched." The Special Assistant to the
President requested extra copies to distribute, and Senator
Conrad Burns (R-MT) requested an extra copy to present to the
Senate Committee on Labor and Human Resources.
>From March 1993 to April 1994, Ms. Wilson served as a publicliaison officer and a member of the planning committee for the
ATSDR sponsored Conference on Low-Level Exposure to
Chemicals and Neurobiologic Sensitivity. She was also one of
three patients to make a presentation at the conference which she
did via telephone.
In 1994, CIIN/EARN initiated the steering committee for the
National Coalition for the Chemically Injured. Ms. Duehring and
Ms. Wilson co-chaired the committee. In 1995, the steering
committee finished the organizational plan for the coalition and
turned it over to an elected Board of Directors.
In December, Ms. Duehring was awarded the 1997 Right
Livelihood Award for her research into the sources and effects of
MCS. The Right Livelihood Award is known as the Alternative
Nobel Prize and is awarded to people working toward a
At the request of the US Interagency Taskforce on Multiple
Chemical Sensitivities, CIIN prepared a report on MCS as a
global health problem. The report, written in 1995, documented
MCS health problems in 36 countries. CIIN was the only group
to be asked to make a presentation to the taskforce.
OUR TOXIC TIMES The monthly magazine of CIIN
The Chemical Injury Information Network publishes a monthly
magazine called Our Toxic Times (OTT). It covers a wide range
of pertinent information for those concerned about Multiple
Chemical Sensitivity, from the technical to the practical. It also
contains advertisements, usually pertaining to living or dealing with
MCS or chemical injury. CIIN appreciates the support of these
advertisers but does NOT guarantee or endorse any products or
services. Also, the magazine is not a substitute for medical, legal,
or other professional services.
CIIN is interested in inquiries into writing articles for OTT. The
phone number for the magazine is the same as for the Chemical
Injury Information Network: 406-547-2255.
* Algeria, Argentina, Australia, Austria, Bahamas, Belgium,
Brazil, Canada, Costa Rica, Croatia, Czech Republic, Denmark,
England, Finland, France, Germany, Greece, Hong Kong, India,
Ireland, Mexico, New Zealand, Netherlands, Northern Ireland,
Norway, Pakistan, Philippines, Puerto Rico, Russia, Scotland,
South Africa, Sweden, United States, Venezuela, and Wales.
Our Toxic Times back issues. 7/90 to 6/94 - $1.50/copy;
7/94 to present - $3/copy. (Unless otherwise specified, the
most recent past issue(s) will be sent.)
Environmental Directory contains over 200 MCS support
groups and related environmental groups. $5
Non-Toxic Buying Guide lists products ranging form
less-toxic construction materials to personal hygiene products.
Over 200 suppliers. $7.50 (Low-income $5)
Chemical Injury Information Network Membership Directory.
$20 for 3.5"disk; $50 for print out. Upon request, a list of
CIIN members in your state will be provided at no cost. For a
copy of another state's members, please send $2 for the first
state and $1.50 for each additional state.
Chemical Profiles are fully referenced abstracts containing
trade names, synonyms, exposure standards, adverse health
effects, usage, and more. $2. per individual profile.
Bibliography of food allergy, MCS, and the health effects of
chemicals. Contains over 1,000 references. $10.40 Order
Chemical Exposures contains the components of products in
everyday use. $2. Order No. 0229-CIIN-93-006R
Rich Murray: Serious symptom syndrome summary:
Aspartame (NutraSweet, Equal, Canderel, Benevia) is reported by
scientific studies and case histories to be toxic: * headaches
* many body and joint pains (or burning, tingling, tremors, twitching,
spasms, cramps, or numbness) * fever, fatigue
* "mind fog", "feel unreal", poor memory, confusion, anxiety,
irritability, depression, mania, insomnia, dizziness, slurred speech,
ringing in ears, sexual problems, poor vision, hearing, or taste
* red face, itching, rashes, burning eyes or throat,
dry mouth or eyes, mouth sores * hair loss
* obesity, bloating, edema, anorexia,
poor or excessive hunger or thirst * breathing problems
* nausea, diarrhea or constipation * coldness * sweating
* racing heart, high blood pressure, erratic blood sugar levels
* seizures * birth defects * brain cancers * addiction
* aggrivates diabetes, autism, ADHD, allergies,
and interstitial cystitis (bladder pain).
Almost all are typical of chronic methanol-formaldehyde toxicity:
for detailed review http://www.dorway.com/barua.html
Dr. J. Barua (ophthalmic surgeon), Dr. Arun Bal (surgeon)
Emerging facts about aspartame.
Journal Of The Diabetic Association Of India 1995; 35 (4):
(79 references) barua@...
"...the total amount of methanol absorbed will be approximately
10% of aspartame ingested. An EPA assessment of methanol states
that methanol, 'is considered a cumulative poison due to the low rate
of excretion once it is absorbed. The absorbed methanol is then
slowly converted to formaldehyde...'"
"Reaction of formaldehyde with DNA has been observed,
by spectrophotometry and electron microscopy, to result in
Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X,
Fernandez-Lopez JA, Alemany M ["Trok-ho"]
Formaldehyde derived from dietary aspartame binds to tissue
components in vivo. Life Sci 1998 Jun 26; 63(5): 337-49.
Departament de Bioquimica i Biologia Molecular, Facultat de Biologia,
Universitat de Barcelona, Spain.
Maria Alemany, PhD (male) alemany@...
RTM: Tholen: Diet Coke has 5 ppm formaldehyde from aspartame
For 6 cans of diet soda, this is 5 times the daily limit of 1 PPM for
formaldehyde in drinking water, set by the EPA.
Dr. Woodrow C. Monte Aspartame: methanol, and the public health.
Journal of Applied Nutrition 1984; 36 (1): 42-54.
(62 references) Professsor of Food Science
Director of the Food Science and Nutrition Laboratory
Arizona State University, Tempe, Arizona 85287
6411 South River Drive #61 Tempe, Arizona 85283-3337
The methanol from 2 L of diet soda, 5.6 12-oz cans, 20 mg/can, is
112 mg, 10% of the aspartame. The EPA limit for water is 7.8 mg daily
for methanol (wood alcohol), a deadly cumulative poison. Many users
drink 1-2 L daily. The reported symptoms are entirely consistent
with chronic methanol toxicity. (Fresh orange juice has 34 mg/L, but,
like all juices, has 16 times more ethanol, which strongly protects
Formaldehyde, also known as formalin, formal, and methyl aldehyde, is a
colorless liquid or gas with a pungent odor. It is generally known as a
disinfectant, germicide, fungicide, defoamer, and preservative.
Formaldehyde is found in adhesives, cosmetics, deodorants, detergents,
dyes, explosives, fertilizer, fiber board, garden hardware, germicide,
fungicide, foam insulation, synthetic lubricants, paints, plastic,
rubber, textile, urethane resins, and water softening chemicals.
Inhalation of vapors produces irritation to the eyes, nose, and throat
and frequently results in upper respiratory tract irritation, coughing,
and bronchitis. Asthma may occur in sensitive individuals. Severe
exposure to fumes may lead to chemical pneumonia. Skin reactions after
exposure to formaldehyde are very common because the chemical can be
both irritating and allergy-causing. In addition, formaldehyde is
involved in DNA damage and inhibits its repair.
Formaldehyde is a suspected human carcinogen and has been shown to
produce mutations and abnormal organisms in bacterial studies.
Formaldehyde fumes are liberated from plywood, particleboard, and
chipboard, as well as urea formaldehyde foam insulation. Symptoms
associated with exposure to formaldehyde fumes include mucous membrane
irritation, upper respiratory tract irritation, eye irritation, skin
rashes, itching, nausea, stuffy nose, headaches, dizziness, and general
Toxicity is primarily related to the presence of formaldehyde gas.
Toxicity may be relatively inconspicuous and nonspecific in nature.
Patients suffering from formaldehyde toxicity have been misdiagnosed as
having asthma, bronchitis, anxiety, depression, or hypochondria. Severe
prolonged vomiting and diarrhea in infants may be related to chronic
exposure to formaldehyde fumes. An individual may become sensitized to
formaldehyde following repeated exposure to these fumes.
If you have any questions or concerns about formaldehyde levels in your
home, contact the office of air pollution control, your local or state
Department of Health, or the American Lung Association office nearest
Aspartame Toxicity Information Center Mark D. Gold
mgold@... 12 East Side Drive #2-18 Concord, NH 03301
"Scientific Abuse in Aspartame Research"
How a Public Relations Campaign Deceives the Public About Formaldehyde
Poisoning From Aspartame October 15, 2000
I have recently been sent some information about aspartame and
formaldehyde that looks like it might be part of one last public
relations campaign to claim the chemical is 'safe'. The formaldehyde
exposure number cited in the text is off by a factor of over 400,000
and would not be taken seriously by knowledgable scientists.
The scientific literature cited has clearly not been read by the author.
However, since a few consumers might inadvertently take the text
seriously, I have chosen to point out some of the more obvious problems
with the text.
> A simple MEDLINE search reveals that the levels ofThe truth is that there is no MEDLINE summary showing an exposure to or
> formaldehyde they are talking about (30 micrograms after the
> ingestion of 200 mg/kg/day of aspartame for 11 days) are
> well within 'safe' levels, even though 200 mg/kg is equal to
> about 60 Diet Cokes per day(!).
an accumulation of 30 micrograms (ug) of formaldehyde in humans after
ingestion of 200 mg/kg/day of aspartame. This figure appears to be
either fabricated or caused by some serious math errors. The actual
figure can be calculated quite easily and is approximately 61.3
milligrams (mg) for ingestion of one liter of diet soda.
The actual measured amount of aspartame in one liter of diet soda is
approximately 600 mg. [Ref. 1]. If a 60 kg (132 lbs) woman ingested one
liter of diet soda, she would be ingesting 10 mg/kg of aspartame:
600 mg aspartame / 60 kg body weight = 10 mg/kg
Aspartame breaks down into 10.9% methanol by weight [Ref. 2]. So that
the amount of methanol obtained from 600 mg of aspartame is:
600 mg aspartame * 10.9% = 65.4 mg of methanol
Methanol converts to formaldehyde in the body. [Note: Methanol from
fruit and alcoholic beverages does not convert to formaldehyde because
of protective factors/chemicals in the foods. See:
Methanol [CH(3)OH] has a molecular weight of
approximately 32.0. Formaldehyde [HCHO] has a molecular weight of
approximately 30.0. Therefore, 65.4 mg of methanol converts to:
65.4 mg methanol * ( 30.0 / 32.0 ) = 61.3 mg of formaldehyde.
If we had used a dose mentioned by the author in the industry public
relations (PR) article of 200 mg/kg instead of an easily-obtainable
dose of 10 mg/kg, the formaldehyde exposure would be 20 times greater or
1,226 mg of formaldehyde. If we used the length of exposure mentioned
in this PR article of 11 days, the exposure to formaldehyde would be a
further 11 times greater or 1,226 * 11 = 13,486 mg of formaldehyde.
The author of the PR article was off by a factor of:
(13,486 mg * 1,000 micrograms/mg) / 30 micrograms = 449,533 !
Some scientists might argue that only 70 - 75% of the methanol from
aspartame is absorbed and of that amount, approximately 90%
is converted into formaldehyde during the metabolic process [Ref. 3].
Even if true, it is clear that the exposure to formaldehyde is somewhere
from 283,000 to 449,533 times what was mentioned in the PR piece.
Using these figures, the exposure to formaldehyde from a 600 mg dose of
aspartame would be:
61.3 mg * 72.5% * 90% = 40 mg of formaldehyde
Rather than discussing an unobtainable daily dose of 200 mg/kg, it is
preferable to discuss a very easily obtainable dose of 10 mg/kg of
aspartame. Actually, a large number of people have reported to this
author ingesting far in excess of this amount on a daily basis.
Even the industry's own research shows that higher dosages are
easily-obtainable by consumers [Ref. 4].
An exposure to a daily dose of 40.0 mg to 61.3 mg of formaldehyde is
clearly enough to cause gradual damage (without even considering
aspartame's excitotoxin that would likely worsen the damage
as discussed at:
The daily dose of airborne formaldehyde exposure that was shown
to cause irreversible genetic damage [Ref. 5] was:
2.25 ppm formaldehyde (average) ~= 3.375 mg/m3
3.375 mg/m3 * 10 m3/workday = 33.75 mg/day (for a
The genetic damage from formaldehyde exposure at approximately 33.75
mg/day was seen after many years of exposure. The longer the exposure,
the more genetic damage.
It is important to keep in mind that the health effects of methanol are
different in humans as compared to rodents and non-human primates [Ref.
6], so experiments of the health effects of aspartame in rodents and
non-human primates might not apply readily to health effects in humans.
Methanol is many times more toxic to humans than to rodents.
Exposure to formaldehyde at levels much lower than the 33.75 mg per day
(that causes irreversible genetic damage) has been shown to cause
musculoskeletal problems, cardiovascular symptoms, gastrointestinal
problems, and a wide range of other chronic toxicity symptoms.
Formaldehyde exposure, especially in the presence of co-exposure to an
excitotoxin from aspartame appears to cause gradual neurological damage
and immunological system changes. Please see discussions at both:
http://www.holisticmed.com/aspartame/methanol.faq for details
and scientific references related methanol and formaldehyde toxicity.
The study by Trocho et al. [Ref. 7] showed that exposure to a single
dose of 10 mg/kg of aspartame led to the accumulation of formaldehyde
in the body. The accumulation of formaldehyde was seen throughout the
body, in the organs (liver, kidneys, brain) and tissues. (See:
The level of formaldehyde accumulation was calculated by Trocho et al.
to be from 5% of the total methanol levels of aspartame given.
For every 600 mg of aspartame (a 10 mg/kg dose in a 60 kg woman),
the amount of formaldehyde estimated to accumulate is:
61.3 mg of formaldehyde * 5% = 3.065 mg of formaldehyde
The research on formaldehyde toxicity and damage is based upon exposure
only. If formaldehyde from aspartame accumulates in organs and tissues
as the Trocho et al. experiment appears to demonstrate, then it is like
a ticking time bomb for those who ingest aspartame (even if they have
not yet experienced symptoms).
> Well, this published MEDLINE study states that the safe levelThis is a complete misrepresentation of the formaldehyde research.
> of formaldehyde consumption for humans is 3 mg/kg/day. So
> someone who weighs 70kg (154 pounds) can safely
> consume 70 x 3 = 210 milligrams of formaldehyde per day.
Formaldehyde is not readily abosrbed from foods [Ref. 8]. But the
methanol in aspartame is readily and quickly absorbed
and then converted into formaldehyde once in the body [Ref. 9, Ref. 10].
(Methanol in fruits has protective factors/chemicals to prevent
"Ingestion represents a minor route of [formaldehyde] exposure
because the dilution factor and the binding to the macromolecules
present in food reduce substantially the [formaldehyde] concentration
that enters into contact with the gastrointestinal mucosa"
(Restani 1991) [Ref. 8]
Therefore, any comparison to formaldehyde in foods, is useless.
A closer comparison (but still not ideal) is a comparison to
the inhalation toxicity of formaldehyde since formaldehyde
is easily introduced into the bloodstream through inhalation or from
methanol derived from aspartame ingestion. The toxicity differences
between inhalation of formaldehyde and formaldehyde derived from
aspartame appear to relate
1.Aspartame also breaks down into an excitotoxin that would be
expected to increase the toxicity of the formaldehyde and its
metabolite, formic acid. Please see discussions at both:
2.Inhalation exposure to formaldehyde likely leads to a greater
exposure of formaldehyde to organs other than the liver. But the Trocho
et al study makes it clear that at least some of the formaldehyde
derived from aspartame is distributed to other organs and tissues.
To conclude, the 30 microgram figure was obviously off by a factor of
over 400,000. The amount of formaldehyde exposure is more than what has
been seen to cause chronic toxicity in independent formaldehyde
exposure research. When one considers
1) the total formaldehyde exposure,
2) the long term exposure to and accumulation of formaldehyde,
3) the excitotoxin obtained from aspartame that would
likely increase the toxicity of the formaldehyde,
4) the permanent damage that can result from chronic formaldehyde
5) the huge numbers of people reporting serious health problems from
long-term aspartame use
6) the fact that independent controlled human studies nearly always find
problems with aspartame (even though the experiments are quite short),
it is a good idea to avoid any aspartame ingestion.
Tsang, Wing-Sum, et al., 1985. "Determination of Aspartame and Its
Breakdown Products in Soft Drinks
by Reverse- Phase Chromatography with UV Detection,"
Journal Agriculture and Food Chemistry,
Vol. 33, No. 4, page 734-738.
Aspartame is composed of: C(14) O(5) N(2) H(18) [See Journal of AOAC
International, Volume 76, No. 2, 1993: "Determination of Aspartame and
Its Major Decomposition Products in Foods."]
The molecular weights are:
C : 12 * 14 = 168
O : 16 * 5 = 80
N : 14 * 2 = 28
H : 1 * 18 = 18
Total = 294
The total molecular weight of methanol is approximately 32.0 as
described above. Therefore, aspartame breaks down into:
(32.0 / 294) * 100 = 10.9% methanol
Kavet, Robert, Kathleen M. Nauss, 1990. "The Toxicity of Inhaled
Methanol Vapors," Critical Reviews in Toxicology, Volume 21, Issue 1,
Porikos, Katherine P., Theodore B. Van Italie, 1984. "Efficacy of
Low-Calorie Sweeteners in Reducing Food Intake: Studies with Aspartame"
In: Stegink, L., Filer L., 1984. "Aspartame: Physiology and
Biochemistry," Marcel Dekker, Inc., N.Y., page 273-286.
Shaham, J., Y. Bomstein, A. Meltzer, Z. Kaufman, E. Palma, J. Ribak,
1996. "DNA--protein Crosslinks, a Biomarker of Exposure to
Formaldehyde--in vitro and in vivo Studies," Carcinogenesis, Volume 17,
No. 1, page 121-125.
Roe, O., 1982. "Species Differences in Methanol Poisoning,"
CRC Critical Reviews In Toxicology, October 1982, page 275-286.
Trocho, C., et al., 1998. "Formaldehyde Derived From Dietary Aspartame
Binds to Tissue Components in vivo," Life Sciences, Vol. 63, No. 5, pp.
Restani, Patrizia, Corrado Galli, 1991. "Oral Toxicity of Formaldehyde
and Its Derivatives," Critical Reviews in Toxicology, Volume 21, Issue
5, pages 315-328.
Haggard, H., L. Greenberg, 1939. "Studies in the absorption,
distribution and elimination of alcohol IV. The elimination of methyl
alcohol," Journal of Pharmacology and Experimental Therap., Volume 66,
Stegink, Lewis, 1984. "Aspartame Metabolism in Humans: Acute Dosing
Studies," In: Stegink, L., Filer L., 1984. "Aspartame: Physiology and
Biochemistry," Marcel Dekker, Inc., N.Y., page 509-553.
Arch Environ Health 2001 Jul-Aug;56(4):300-11
Embryo toxicity and teratogenicity of formaldehyde. [100 references]
Thrasher JD, Kilburn KH.
Sam-1 Trust, Alto, New Mexico, USA.
[127K full text]
Jack D. Thrasher, Ph.D. toxicology@...
Sam-1 Trust, P.O. Box 874, Alto, New Mexico 88312
Off: (505) 336-8312 Fax: (425) 675-7379
Kaye H. Kilburn, M.D. kilburn@...
University of Southern California
Keck School of Medicine
Environmental Sciences Laboratory
2025 Zonal Avenue, CSC 201, Los Angeles, California 90033
text Dec, 1997 "Chemical Brain Injury"
C-14 [radioactive labelled] formaldehyde crosses the placenta and
enters fetal tissues. The incorporated radioactivity is higher in fetal
organs (i.e., brain and liver) than in maternal tissues. The
incorporation mechanism has not been studied fully, but formaldehyde
enters the single-carbon cycle and is incorporated as a methyl group
into nucleic acids and proteins.
Also, formaldehyde reacts chemically with organic compounds (e.g.,
deoxyribonucleic acid, nucleosides, nucleotides, proteins, amino acids)
by addition and condensation reactions, thus forming adducts and
deoxyribonucleic acid-protein crosslinks.
The following questions must be addressed: What adducts (e.g.,
N-methyl amino acids) are formed in the blood following formaldehyde
inhalation? What role do N-methyl-amino adducts play in
alkylation of nuclear and mitochondrial deoxyribonucleic acid, as well
as mitochondrial peroxidation?
The fact that the free formaldehyde pool in blood is not affected
following exposure to the chemical does not mean that formaldehyde is
not involved in altering cell and deoxyribonucleic acid characteristics
beyond the nasal cavity.
The teratogenic effect of formaldehyde in the English literature has
been sought, beginning on the 6th day of pregnancy (i.e., rodents)
(Saillenfait AM, et al. Food Chem Toxicol 1989, pp 545-48;
Martin WJ. Reprod Toxicol 1990, pp 237-39;
Ulsamer AG, et al. Hazard Assessment of Chemicals; Academic Press,
1984, pp 337-400;
and U.S. Department of Health and Human Services. Toxicological Profile
of Formaldehyde; ATSDR, 1999
[references 1-4, respectively, herein]).
The exposure regimen is critical and may account for the differences in
outcomes. Pregnant rats were exposed (a) prior to mating, (b) during
mating, (c) or during the entire gestation period. These regimens
(a) increased embryo mortality;
(b) increased fetal anomalies (i.e., cryptochordism and aberrant
(c) decreased concentrations of ascorbic acid; and
(d) caused abnormalities in enzymes of mitochondria, lysosomes, and the
The alterations in enzymatic activity persisted 4 mo following birth.
In addition, formaldehyde caused metabolic acidosis,
which was augmented by iron deficiency.
Furthermore, newborns exposed to formaldehyde in
utero had abnormal performances in open-field tests.
Disparities in teratogenic effects of toxic chemicals are not unusual.
For example, chlorpyrifos has not produced teratogenic effects in rats
when mothers are exposed on days 6-15
(Katakura Y, et al. Br J Ind Med 1993, pp 176-82
[reference 5 herein]) of gestation
(Breslin WJ, et al. Fund Appl Toxicol 1996, pp 119-30;
and Hanley TR, et al. Toxicol Sci 2000, pp 100-08
[references 6 and 7, respectively, herein]).
However, either changing the endpoints for measurement or exposing
neonates during periods of neurogenesis (days 1-14 following birth) and
during subsequent developmental periods produced adverse effects. These
effects included neuroapoptosis, decreased deoxyribonucleic acid and
ribonucleic acid synthesis, abnormalities in adenylyl cyclase cascade,
and neurobehavioral effects
(Johnson DE, et al. Brain Res Bull 1998, pp 143-47;
Lassiter TL, et al. Toxicol Sci 1999, pp 92-100;
Chakraborti TK, et al. Pharmacol Biochem Behav 1993, pp 219-24;
Whitney KD, et al. Toxicol Appl Pharm 1995, pp 53-62;
Chanda SM, et al. Pharmacol Biochem Behav 1996, pp 771-76;
Dam K, et al. Devel Brain Res 1998, pp 39-45;
Campbell CG, et al. Brain Res Bull 1997, pp 179-89;
and Xong X, et al. Toxicol Appl Pharm 1997, pp 158-74
[references 8-15, respectively, herein]).
Furthermore, the terata caused by thalidomide
is a graphic human example in which the animal model and timing of
exposure were key factors
(Parman T, et al. Natl Med 1999, pp 582-85;
and Brenner CA, et al. Mol Human Repro 1998, pp 887-92
[references 16 and 17, respectively, herein]).
Thus, it appears that more sensitive endpoints (e.g., enzyme activity,
generation of reactive oxygen species, timing of exposure) for the
measurement of toxic effects of environmental agents on embryos,
fetuses, and neonates are more coherent than are gross terata
observations. The perinatal period from the end of organogenesis to the
end of the neonatal period in humans approximates the 28th day of
gestation to 4 wk postpartum. Therefore, researchers must investigate
similar stages of development
(e.g., neurogenesis occurs in the 3rd trimester in humans
and neonatal days occur during days 1-14 in rats and mice, whereas
guinea pigs behave more like humans).
Finally, screening for teratogenic events should also include exposure
of females before mating or shortly following mating.
Such a regimen is fruitful inasmuch as environmental
agents cause adverse effects.
Publication Types: Review Review, Tutorial PMID: 11572272
Discussion and Analysis of the Papers:
FA was distributed to all organs in the adult, the placenta and
fetus (Table 1), which was similar to that reported in male F344 rats,
guinea pigs and monkeys. (25,26).
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.
The DNA fraction contained 20 % and 50% of total incorporated
radioactivity in the maternal and fetal liver at 6 and 24 hours when
compared to the acid insoluble fraction (Fig. 1).
Of primary interest is that the incorporated radioactivity persisted
longer in the fetal liver and brain when compared to the mothers.
Also, since FA is a precursor of a number of biological compounds, it
would have been of prime interest to determine what fraction resulted
from either metabolic incorporation or from chemical reactivity of FA
(e.g. crosslinks, adduction, methylation) with biological molecules
(DNA, proteins, polypeptide, amino acids, etc.).
FA undergoes addition (adducts and alkylation) and condensation
(methene bridges) reactions with proteins and amino acids (27) as well
as nucleic acids and nucleosides/tides. (28)
It is a mutagen, crosslinking agent and an immunogen (28-30).
Free FA concentrations in the blood are 2.24+- 0.07 (rats), 1.84+- 0.15
(Rhesus monkeys) and 2.61+- 0.14 (humans) ug/g of blood [ppm],
which did not change following either acute or subchronic inhalation of
Thus, it appears that additional information is required on addition
and condensation products of amino acids, polypeptides, nucleoside, etc.
of the blood, generated by FA exposure.
An increase of N-methyl amino acids would produce endogenous FA, which
may have a significant role in mitotic and apoptosis processes.
FA generators are responsible for FA formation in tumors and have an
impairment of liver antioxidant mechanisms and functional integrity of
FA had adverse effects on zygotes/embryos and bone marrow cells (Tables
2 and 3). The embryos showed cytological injury and high rate of
mortality, while bone marrow cells had increased rates of chromosome
aberrations and aneuploidy.
Similar observations on chromosomes of peripheral lymphocytes have been
reported for anatomy and mortuary students. (42-44)
Classroom exposure to FA at 1.5 to 3.17 mg/m3 was associated with
increased frequency of sister chromatid exchanges, aberrations and
micronuclei. Concentrations less 1 mg/m3 had no effect on lymphocyte
chromosomes, but caused micronuclei in nasal and oral exfoliative cells
and changes in lymphocyte subsets (increase in CD19 and decreases in
CD4, CD5 and H/S ratio. (45,46)
With respect to the effect of FA on embryos additional research is
needed. FA is an alkylating agent. Treatment of C3H transplacentally
with N-ethyl-N-nitrosourea (alkylating agent) has caused
primordial germ cell mutations. (47)
Also, treatment of female mice within hours after mating with ethyl
methanesulfanate, ethyl nitrosourea and ethylene oxide resulted
in fetal deaths and malformations. (48-51)
Thus, further investigation into the zygote/embryonic effects of FA
should follow the protocols established for other alkylating agents
with attention to the role of potential methyl donors,
e.g. N-methyl amino acids.
FA exposure throughout gestation caused a decreased DNA and RNA
concentrations, increased weights of bodies and organs (thymus, heart,
kidneys and adrenals) and decreased in the weights of lung and liver
(Table 3). Microscopy and histochemical observations revealed other
abnormalities: involution of lymphoid tissue, numerous extra-medullary
hemopoietic centers, decreased glycogen content (myocardium) and liver,
decreased AA content of whole fetus and fetal and maternal liver.
AA is an antioxidant, produced from glucuronate via the uronic acid
pathway, which also is the intermediary route for synthesis of pentoses.
The decreased AA content may have resulted from either the utilization
of AA as an antioxidant or by interference (inhibition?) of the uronic
It is difficult to interpret the meaning of the decreased DNA and the
increased RNA contents of the organs. However, treatment of adult male
rats by FA injection was reported to decrease the DNA content of testis
and prostate and a decrease of protein content of the prostate and
Cytopathology of organs and alterations of mitochondria,
ER and lysosome enzymatic were observed in fetuses following FA
inhalation (Table 4).
Organ cytopathology included increased ploidy, micronecrotic loci,
extramedullary hematopoeitec enters, and degeneration of kidney
glomeruli. Concomitant were changes in enzymatic activity of as follows:
mitochondria (MDH, SDH, LDH decreased, while GDH increased);
ER and lysosomes (ATPase increased while inosine diphosphatase and
b-glucorinidase decreased). The impairment lasted in the organs to 4
months of age.
In addition, N-acetylneuraminic concentration increased in maternal and
fetal tissues. The changes in the enzymatic activity and
N-acetyleneuraminic acid correlated with increased fetal mortality.
Finally, the development of postnatal behavior was also adversely
affected (Table 6).
FA has effects on mitochondrial enzymes, glutathione concentrations and
bile production in the liver of many species, including humans. (53)
FA inhibits the uptake of phosphate by mitochondria, (54,55) and causes
the release of GPT, SDH, GSSG and malondialdehyde into the perfusate of
isolated livers. (56)
Intraperitoneal injection results in a 2-fold increase in bile and a
significant decrease in glutathione of the liver, lungs and brains. (57)
An electron microscopic investigation of the perfused isolated livers
showed destruction of the mitochondria (ruptured membranes, loss of the
cristae) and some damage to the endoplasmic reticulum. (56)
The protection of the liver from FA toxicity appears to be dependent
upon glutathione by formation of the adduct S-hydroxymethylglutathione.
Thus, the observed effect of FA on mitochondrial and ER functions
during embryo/fetal development is also demonstrable in the adult liver.
FA caused preimplantation, prenatal and postnatal abnormalities. The
prenatal effects were demonstrable as anomalies and aberrancies in
blood buffering capacity with metabolic (formate?) acidosis. The major
anomalies were an increased frequency of cryptochordism, a
decrease/delay in ossification centers of the hyoid, metacarpus and
metatarsal bones, delay in eruption of incisors and a decrease in body
Blood pH decreased in the fetus, while the pCO2 (hypercapnia) increased
in the fetus and the mother. The true bicarbonates and CO2 were
unaffected by FA alone, but increased with iron-deficiency in the fetus
The presence of iron-induced deficiency augmented these abnormalities,
along with increased embryo mortality .
The postnatal effect of FA was tested by maze performance. Open field
tests demonstrated an increase in motor activity, increase in standing
and appearance of emotion.
In sexually mature rats there was an increase in search activity.
FA is metabolized to formate. Alcohols, particularly methanol and
ethanol, are metabolized to formate and lactate via an aldehyde.
The toxicity of alcohols and formalin in humans and animals includes
metabolic acidosis (59-61). Alcohol toxicity generates free radicals,
cause an increase in malondialdehyde, and induce lipid peroxidation
resulting in DNA single strand breaks (62-66).
FA and alcohols probably affect embryos and the fetus via mitochondrial
Ethanol and environmental agents trigger apoptotic neurodegeneration in
the developing brain (67,68).
Oxygen stress, such as that caused by free radical generation, is
associated with apoptotic cell death and fragmentation of mitochondrial
Moreover, FA via formaldehyde generators, e.g. alkylating agents,
initiates apoptosis (72-74).
Mitochondria are the suicide organelles and control apoptosis (75-78).
Thus, subtle birth defects (autism, low birth weight, fetal alcohol
syndrome, etc.) are probably best understood by investigating in utero
oxidative stress and mitochondrial damage, rather than by standard FA
teratogenic research (79-83).
Mutat Res 2002 Feb 15;514(1-2):115-23
Sister chromatid exchange in pathology staff occupationally exposed to
Shaham J, Gurvich R, Kaufman Z. judiths@...
National Institute of Occupational and Environmental Health
P.O Box 3 Raanana 43100, Israel
+972 9 - 770 7200 Fax- +972 9 - 771 4969
Dr. Judith Shaham, MD MOccH
972-3-5404786 fax 972-3-5497293
Head of Occupational Cancer Department
Dr. Shaham was the Chairman of the Organizing Committee of the 14th
International Conference on Epidemiology in Occupational Health that
was held in Herzlia, Israel, in 1999.]
Sister chromatid exchange (SCE) was measured in peripheral lymphocytes
of 90 workers from 14 hospital pathology departments in Israel who were
occupationally exposed to formaldehyde (FA) and of 52 unexposed workers
from the administrative section of the same hospitals.
The mean exposure period to FA was 15.4 years (range 1-39). The results
of SCEs are expressed in two variables:
(a) mean number of SCEs per chromosome and (b) proportion of high
frequency cells (cells with more than eight SCEs). A high correlation
was found between these two variables.
The adjusted means of both SCEs variables were significantly higher
among the exposed compared with that of the unexposed group (P<0.01).
Adjustment was made for age, sex, smoking habits, education
workers and origin. Evaluation of the influence of years of exposure on
the frequency of SCEs showed that the two variables of SCEs were higher
among those who were exposed to FA for 15 or more than among those with
less than 15 years of exposure.
Concerning levels of exposure, both variables of SCEs were the same in
the low and in the high levels of exposure sub-groups.
However, among the smokers, both variables of SCEs were higher in the
high exposure sub-group than in the low exposure sub-group.
Our finding of a significant increase of SCEs frequency in peripheral
lymphocytes in pathology staff indicates a potential cytogenetic hazard
due to FA exposure. We conclude that our data indicate that FA is
mutagenic to humans. PMID: 11815250
Rich Murray, MA Room For All rmforall@...
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