Woodrow C. Monte Ph.D.
Professor of Food Science
6411 South River Drive  #61
Tempe, Arizona   85283-3337
United States of America
Phone/Fax 1 602-965-6938
woody.monte@asu.edu

JOURNAL OF APPLIED NUTRITION, VOLUME 36, NUMBER 1, 1984
REPORT ASPARTAME:  METHANOL AND THE PUBLIC HEALTH

Abstract

Aspartame (L-asparty-L-phenylalanine methyl ester), a new sweetener
marketed under the trade name NutraSweet*, releases into the human
bloodstream one molecule of methanol for each molecule of aspartame
consumed.

  This new methanol source is being added to foods that have
considerably reduce caloric content and, thus, may be consumed in

large amounts. Generally, none of these foods could be considered
dietary methanol sources prior to addition of aspartame. When diet sodas
and soft drinks, sweetened with aspartame, are used to replace fluid
loss during exercise and physical exertion in hot climates, the intake
of methanol can exceed 250 mg/day or 32 times the Environmental
Protection Agency's recommended limit of consumption for this cumulative
toxin(8).

  There is extreme variation in the human response to acute methanol
poisoning, the lowest recorded lethal oral dose being 100 mg/kg with one
individual surviving a dose over ninety times this level (55). Humans,
due perhaps to the loss of two enzymes during evolution, are more
sensitive to methanol than any laboratory animal; even the monkey is not
generally accepted as a suitable animal model (42). There are no human
or mammalian studies to evaluate the possible mutagenic, teratogenic, or
carcinogenic effects of chronic administration of methyl alcohol (55).

  The average intake of methanol from natural sources varies but limited
data suggests an average intake of considerably less than 10 mg/day (8).
Alcoholics may average much more, with a potential range of between 0
and 600 mg/day, depending on the source and in some cases the quality of
their beverages (15).

  Ethanol, the classic antidote for methanol toxicity, is found in
natural food sources of methanol at concentrations 5 to 500,000 times
that of the toxin (Table 1). Ethanol inhibits metabolism of methanol and
allows the body time for clearance of the toxin through the lungs and
kidneys (40,46).

  The question asked whether uncontrolled consumption of this new
sweetener might increase the methanol intake of certain individuals to a
point beyond which our limited knowledge of acute and chronic human
methanol toxicity can be extrapolated to predict safety.

  *NutraSweet is a trademark of G.D. Searle & Co.

  Aspartame

  Aspartame (L-aspartyl-L-phenylalanine methyl ester) has recently been
approved as a sweetener for liquid carbonated beverages. It has had wide
acceptance as an additive in many dry food applications after Food and
Drug Administration approval on July 24, 1981 (48).

  The Food and Drug Administration, Dr. Richard Wurtman and myself have
received well over a thousand written complaints relative to aspartame
consumption. By far, the most numerous of these include dizziness,
visual impairment, disorientation, ear buzzing, high SGOT, tunnel
vision, loss of equilibrium, severe muscle aches, numbing of
extremities, pancreatitis, episodes of high blood pressure, retinal
hemorrhaging, menstrual flow changes, and depression. The validity of
these complaints has yet to be scientifically evaluated. However, a
thorough knowledge of just what makes this new sweetener stand apart
from other nutritional substances might aid physicians in making dietary
recommendations for their patients.

  Aspartame (NutraSweet)* is a small molecule made up of three
components: Phenylalanine, aspartic acid, and methanol (wood alcohol)
(47). When digested, these components are released into the bloodstream
(48). Phenylalanine and aspartic acid are both amino acids which are
found in natural proteins (14), and under normal circumstances are
beneficial, if not essential, for health. Proteins are complex molecules
which contain many chemically bonded amino acids. It takes several
enzymes to break these bonds and liberate the amino acids. This is as
slow process and the amino acids are released gradually into the blood
stream (40). The quaternary structure of protein also slows the
digestion of these amino acids; the amino acids in the center of the
protein molecule aren't released until the outer layers of amino acids
on the surface have been swept away. This natural time release process
saves the body from large numbers of any one of these 21 amino acids
being released into the bloodstream at any one time.

  Aspartame requires the breaking of only two bonds for absorption (47).
This happens very quickly with the potential to raise component blood
levels rapidly (52). The methyl ester bond of phenyalanine is the first
to cleave due to its susceptibility to pancreatic enzymes (40). This is
highly unusual; the methyl esters associated with pectin for instance
are completely impervious to all human digestive enzymes (6).

  Amino Acid Components

  Phenylalanine

  Phenylalanine is an essential amino acid, the daily consumption of
which is required to maintain life. However, Dr. Richard J. Wurtman,
Professor of Neuroendocrine Regulation at the Massachusetts Institute of
Technology, presented data to the FDA demonstrating that in humans the
feeding of a carbohydrate with aspartame significantly enhances
aspartame's positive effect on plasma and brain phenylalanine and
tyrosine levels (48 Federal Register at 31379). There are sound
scientific reasons to believe that increasing the brain levels of these
large neutral amino acids could affect the synthesis of
neurotransmitters and in turn affect bodily functions controlled by the
autonomic nervous system (61) (e.g., blood pressure). The proven ability
of aspartame to inhibit the glucose-induced release of serotonin within
the brain may also affect behaviors, such as satiety and sleep (61).

  Aspartic Acid

  Aspartic acid, is not an essential amino acid but is normally easily
utilized for human metabolism. However, under conditions of excess
absorption it has caused endocrine disorders in mammals with markedly
elevated plasma levels of luteinizing hormone and testosterone in the
rat (52) and release of pituitary gonadotropins and prolactin in the
rhesus monkey (58). The amount of luteinizing hormone in the blood is a
major determinant of menstrual cycling in the human female (39).

  Methanol

  Methanol (methyl alcohol, wood alcohol), a poisonous substance (60),
is added as a component during the manufacture of aspartame (47). The
methanol is subsequently released within hours of consumption (51) after
hydrolysis of the methyl group of the dipeptide by chymotrypsin in the
small intestine (40). Absorption in primates is hastened considerably if
the methanol is ingested as free methanol (40) as it occurs in soft
drinks after decomposition of aspartame during storage or in other foods
after being heated (48). Regardless of whether the aspartame-derived
methanol exists in food in its free form or still esterified to
phenylalanine, 10% of the weight of aspartame intake of an individual
will be absorbed by the blood stream as methanol within hours after
consumption (51).

  Methanol has no therapeutic properties and is considered only as a
toxicant (20). The ingestion of two teaspoons is considered lethal in
humans (19).

  Methyl alcohol produces the Methyl alcohol syndrome, consistently,
only in humans and no other test animal, including monkeys (42,54).
There is a clear difference between "toxicity", which can be produced in
every living thing, and the "toxic syndrome" (54).

  The greater toxicity of methanol to man is deeply rooted in the
limited biochemical pathways available to humans for detoxification. The
loss of uricase (EC 1.7.3.3.), formyl-tetrahydrofolate synthetase (EC
6.3.4.3.) (42) and other enzymes (18) during evolution sets man apart
from all laboratory animals including the monkey (42). Tere is no
generally accepted animal model for methanol toxicity (42,59). Humans
suffer "toxic syndrome" (54) at a minimum lethal dose of < 1gm/kg, much
less than that of monkeys, 3-6 g/kg (42,59). The minimum lethal dose of
met·anol in the rat, rabbit, and dog is 9, 5, 7, and 8 g/kg,
respectively (43); ethyl alcohol is more toxic than methanol to these
test animals (43). No human or experimental mammalian studies have been
found to evaluate the possible mutagenic, teratogenic or carcinogenic
effects of methyl alcohol (55), through a 3.5% chromosomal aberration
rate in testicular tissues of grasshoppers was induced by an injection
of methanol (51).

  The United States Environmental Protection Agency in their Multimedia
Environmental Goals for Environmental Assessment recommends a minimum
acute toxicity concentration of methanol in drinking water at 3.9 parts
per million, with a recommended limit of consumption below 7.8 mg/day
(8). This report clearly indicates that methanol:

  "is considered a cumulative poison due to the low rate of excretion
once it is absorbed. In the body, methanol is oxidized to formaldehyde
and formic acid; both of these metabolites are toxic." (8)

  Role of Formaldehyde

  Recently the toxic role of formaldehyde (in methanol toxicity) has
been questioned (34). No skeptic can overlook the fact that,
metabolically, formaldehyde must be formed as an intermediate to formic
acid production (54). Formaldehyde has a high reactivity which may be
why it has not been found in humans or other primates during methanol
poisioning (59). The localized retinal production of formaldehyde from
methanol is still thought to be principally responsible for the optic
papillitis and retinal edema always associated with the toxic syndrome
in humans (20). This is an intriguing issue since formaldehyde poisoning
alone does not produce retinal damage (20).

  If formaldehyde is produced from methanol and does have a reasonable
half life within certain cells in the poisoned organism the chronic
toxicological ramifications could be grave. Formaldehyde is a know
carcinogen (57) producing squamous-cell carcinomas by inhalation
exposure in experimental animals (22). The available epidemiological
studies do not provide adequate data for assessing the carcinogenicity
of formaldehyde in man (22,24,57). However, reaction of formaldehyde
with deoxyribonucleic acid (DNA) has resulted in irreversible
denaturation that could interfere with DNA replication and result in
mutation (37). Glycerol formal, a condensation product of glycerol and
formaldehyde (which may be formed in vivo), is a potent teratogen
causing an extremely high incidence of birth defects in laboratory
animals (52). Even the staunchest critic of formaldehyde involvement in
methanol toxicity admits:

  "It is not possible to completely eliminate formaldehyde as a toxic
intermediate because formaldehyde could be formed slowly within cells
and interfere with normal cellular function without ever obtaining
levels that are detectable in body fluids or tissues." (34)

  Acute Toxicity in Man: "Toxic Syndrome"

  A striking feature of methyl alcohol syndrome is the asymptomatic
interval (latent period) which usually lasts 12 to 18 hours after
consumption. This is followed by a rapid and severe acidosis caused
partially by the production of formic acid (19). Insufficient formic
acid is generated to account for the severity of metabolic acidosis
produced and, therefore, other organic acids may also be involved (32).
Patients may complain of lethargy, confusion, and impairment of
articulation, all frequently encountered signs in moderate central
nervous system (CNS) intoxication's resulting from other toxic compounds
(20).

  Patients may also suffer leg cramps, back pain, severe headache,
abdominal pain, labored breathing, vertigo and visual loss, the latter
being a very important clue to making a diagnosis of methanol poisoning
(20). Other striking clinical features associated only with the oral
administration of methanol are elevated serum amylase and the finding of
pancreatitis or pancreatic necrosis on autopsy (20,55).

  In fatal cases liver, kidneys and heart may show parenchymatous
degeneration. The lungs show desquamation of epithelium, emphysema,
edema, congestion and bronchial pneumonia(12).

  Chronic Human Exposure

  This is the most important aspect of methanol toxicity to those who
are interested in observing the effect of increased methanol consumption
on a population.

  The data presented here were compiled by the Public Health Service.
The individuals studied were working in methanol contaminated
environments. It is interesting to note that the visual signs always
associated with acute toxicity often do not surface under chronic
conditions (20).

  Many of the signs and symptoms of intoxication due to methanol
ingestion are not specific to methyl alcohol. For example, headaches,
ear buzzing, dizziness, nausea and unsteady gait (inebriation),
gastrointestinal disturbances, weakness, vertigo, chills, memory lapses,
numbness and shooting pains in the lower extremities hands and forearms,
behavioral disturbances, and neuritis (55). The most characteristic
signs and symptoms of methyl alcohol poisoning in humans are the various
visual disturbances which can occur without acidosis (55) although they
unfortunately do not always appear (20). Some of these symptoms are the
following: misty vision, progressive contraction of visual fields
(vision tunneling), mist before eyes, blurring of vision, and
obscuration of vision (20,55).

  Alcoholics: Chronic Methanol Consumption

  Alcoholics in general, but particularly those who consume large
quantities of wine or fruit liqueur, would seem, from the available
evidence, to be the only population thus far exposed to consistently
high levels of methanol ingestion (Table 1). The high ethanol/methanol
ration of alcoholic beverages must have a very significant protective
effect, though enzyme kinetics mandate some constant but low level of
methanol metabolism. One could speculate that the delicate balance which
maintains this defense might be jeopardized by the general nutrition
neglect and specifically the folic acid deficiency (21) associated with
the meager food intake of some alcoholics. Alcoholics have a much higher
incidence of cancer and other degenerative diseases, none of which can
be attributed to ethanol alone (56). The fascinating similarities
linking unusual clinical features of methanol toxicity and alcoholism
are worth noting.

  Neuritis:

  Chronic occupational exposure to methanol often produces human
complaints of neuritis with paresthesia, numbing, pricking and shooting
pains in the extremities (4,55).

  Alcoholic polyneuropathy (36) or multiple peripheral neuritis (21)
differs symptomatically from the methanol induced syndrome only in its
first and often exclusive affinity for legs. The unpleasant sensations
of intolerable pain associated with slight tactile stimulation (36) is
not an uncommon anecdotal consumer complaint following long term
consumption of aspartame. In one such case reported to me, my
interpretation of an electromyogram indicated the signs of denervation
indicative of alcoholic polyneuropathy (36). The individual's ischemic
lactate pyruvate curve, before and after fasting, was flat. Less than
six weeks after aspartame consumption ceased the major symptoms subsided
and repetition of these tests produced normal responses, although the
individual still experienced intermittent pain.

  Pancreatitis:

  Methanol is one of the few etiologic factors associated with acute
pancreatic inflammation (16,20). Microscopic findings of pancreatic
necrosis on autopsy have been reported after acute oral methanol
poisoning (55) which marks the end of the latent period.

  There is a generally accepted association between alcoholism and
pancreatitis. Most patients, however, give a history of 5 to 10 years of
heavy drinking before the onset of the first attack (16). The fact that
40% of all cases of acute pancreatitis complaints are attributable to
alcoholics (21), however, must be taken into consideration to avoid
artifactual association. Pancreatitis has been a complaint associated
with aspartame consumption.

  Methanol and the Heart:

  A 21-year-old non-drinking male who had been exposed daily to the fine
dust of aspartame at the packaging plant he had worked for over a year,
was complaining of blurred vision, headaches, dizziness, and severe
depression before his sudden death. An autopsy revealed (aside from the
organ involvement one might expect from methanol toxicity) myocardial
hypertrophy and dilatation with the myocardiopathy and left ventricle
involvement reminiscent of alcoholic cardiomyopathy. Alcoholic
cardiomyopathy, however, typically occurs in 30-55 year old men who have
a history of alcohol intake in quantities comprising 30-50 percent of
their daily caloric requirement over a 10 to 15 year period (56).

  It has been suggested that alcohol is the etiologic factor in at least
50 percent of the cases of congestive cardiomyopathy (56). The
significantly lower hospitalization incidence for coronary disease among
moderate drinkers than among nondrinkers and the protection to coronary
risk afforded the moderate drinker (less than two drinks a day) over the
nondrinker (56) seems contradictory. However, if we implicate methanol
as the etiologic factor, then clearly the nondrinker is at a
disadvantage with a much lower ethanol to methanol ratio (Table 1) when
consuming naturally occurring methanol in a diet otherwise equivalent to
the drinkers. The chronic alcoholic for reasons already proposed might
sacrifice this protection.

  As mentioned below, high temperature canning as developed late in the
19th century should increase significantly the methanol content of
fruits and vegetables. The increased availability and consumption of
these food products in various countries over the years may parallel
better than most other dietary factors the increase in incidence of
coronary disease in their populations. Cigarette smoke, a known coronary
risk factor, contains four times as much methanol as formaldehyde and
only traces of ethanol.

  Ethanol and Folic Acid

  The importance of ethanol as an antidote to methanol toxicity in
humans is very well established in the literature (46,55). The timely
administration of ethanol is still considered a vital part of methanol
poisoning management (11,12,19,20,50). Ethanol slows the rate of
methanol's conversion to formaldehyde and formate, allowing the body
time to excrete methanol in the breath and urine. Inhibition is seen in
vitro even when the concentration of ethyl alcohol was only 1/16th that
of methanol (62). The inhibitory effect is a linear function of the log
of the ethyl alcohol concentration, with a 72% inhibition rate at only a
0.01 molar concentration of ethanol (2,46).

  Oxidation of methanol, like that of ethanol, proceeds independently of
the blood concentration, but at a rate only one seventh (20) to one
fifth (12) that of ethanol.

  Folacin may play an important role in the metabolism of methanol by
catalyzing the elimination of formic acid (41). If this process proves
to be as protective for humans as has been shown in other organisms
(50,38) it may account, in part, for the tremendous variability of human
responses to acute methanol toxicity. Folacin is a nutrient often found
lacking in the normal human diet, particularly during pregnancy and
lactation (14).

  Methanol Content of Aspartame Sweetened Beverages

  An average aspartame-sweetened beverage would have a conservative
aspartame content of about 555 mg/liter48, (51) and therefore, a
methanol equivalent of 56 mg/liter (56 ppm). For example, if a 25 kg
child consumed on a warm day, after exercising, two-thirds of a two-
liter bottle of soft drink sweetened with aspartame, that child would be
consuming over 732 mg of aspartame (29 mg/kg). This alone exceeds what
the Food and Drug Administration considers the 99+ percentile daily
consumption level of aspartame (48). The child would also absorb over 70
mg of methanol from that soft drink. This is almost ten times the
Environmental Protection Agency's recommended daily limit of consumption
for methanol.

  To look at the issue from another perspective, the literature reveals
death from consumption of the equivalent of 6 gm of methanol (55,59). It
would take 200 12 oz. cans of soda to yield the lethal equivalent of 6
gm of methanol. According to FDA regulations, compounds added to foods
that are found to cause some adverse health effect at a particular usage
level are actually permitted in foods only at much lower levels. The FDA
has established these requirements so that an adequate margin of safety
exists to protect particularly sensitive people and heavy consumers of
the chemical. Section 170.22 of Title 21 of the Code of Federal
Regulations mandates that this margin of safety by 100-fold below the
"highest no-effect" level. If death has been caused by the methanol
equivalent of 200 12 oz. cans of aspartame sweetened soda, one hundredth
of that level would be two cans of soda. The relationship of the lethal
dose to the "highest no effect" level has tragically not been determined
for methanol (9,11) but assuming very conservatively that the level is
one tenth of the lethal dose, the FDA regulations should have limited
consumption to approximately 2.4 ounces of aspartame sweetened soft
drink per day.

  The FDA allows a lower safety margin only when "evidence is submitted
which justifies use of a different safety factor." (21.C.F.R.170.22) No
such evidence has been submitted to the FDA for methanol. Thus, not only
have the FDA's requirements for acute toxicity not been met, but also,
no demonstration of chronic safety has been made. The fact that methyl
alcohol appears in other natural food products increases greatly the
danger of chronic toxicity developing by adding another unnatural source
of this dangerous cumulative toxin to the food system.

  Natural Sources of Methanol

  Methanol does appear in nature.

  To determine what impact the addition of a toxin will have on an
environment it is very helpful to accurately determine the background
levels of consumption.

  Fruit and vegetables contain pectin with variable methyl ester
content. However, the human has no digestive enzymes for pectin (6,25)
particularly the pectin esterase required for its hydrolysis to methanol
(26). Fermentation in the gut may cause disappearance of pectin (6) but
the production of free methanol is not guaranteed by fermentation (3).
In fact, bacteria in the colon probably reduce methanol directly to
formic acid or carbon dioxide (6) (aspartame is completely absorbed
before reaching the colon). Heating of pectins has been shown to cause
virtually no demethoxylation; even temperatures of 120*C produced only
traces of methanol (3). Methanol evolved during cooking of high pectin
foods (7) has been accounted for in the volatile fraction during boiling
and is quickly lost to the atmosphere (49). Entrapment of these
volatiles probably accounts for the elevation in methanol levels of
certain fruit and vegetable products during canning (31,33).

  In the recent denial by the Food and Drug Administration of my request
for a public hearing on this issue (13), the claim is made by them that
methanol occurs in fruit juices at an average of 140 parts per million
(a range of between 15-640 parts per million). This often used average
originates from an informative table in a conference paper presented by
Francot and Geoffroy (15). The authors explain that the data presented
in the table "may not" represent their work but "other authors" (15).
There is no methodology given nor is the original source cited and only
the identity of the lowest methanol source, grape juice (12 ppm), and
the highest, black currant (680 ppm), are revealed. The other 22 samples
used to generate this disarmingly high average are left completely to
the imagination. The authors conclude their paper by insisting that "the
content of methanol in fermented or non-fermented beverages should not
be of concern to the fields of human physiology and public health." They
imply that wines "do not present any toxicity" due to the presence of
certain natural protective substances (15). When they present their
original data relating to the methanol content of French wines (range
14-265 ppm) or when the methanol content of any alcoholic beverage is
given, the ration of methanol to ethanol is also presented. Of the wines
they tested, the ratio associated with the highest methanol content (265
ppm) indicates over 262 times as much ethanol present as methanol. The
scientific literature indicates that a fair estimate of methanol content
of commonly consumed fruit juices is on the order of 40 parts per
million (Table 1). Stegink, et al. Points out that some neutral spirits
contain as much as 1.5 grams/liter of methanol (51); what is not
mentioned is the fact that if these spirits are at least 60 proof (30%
ethanol) this still represents the presence of over 200 molecules of
ethanol for every molecule of methanol that is digested. An exhaustive
search of the present literature indicates that no testing of natural
substances has ever shown methanol appearing alone; in every case
ethanol is also present, usually, in much higher concentrations
(15,27,28,30,31,35,44,45). Fresh orange juices can have very little
methanol (0.8 mg/liter), and have a concomitant ethyl alcohol content of
380 mg/liter 28. Long term storage in cans has a tendency to cause an
increase in these levels, but even after three years of storage, testing
has revealed only 62 mg/liter of methanol, with an ethanol content of
484 mg/liter. This is a ratio of almost eight times ethanol/methanol
(28). Testing done recently in Spain showed orange juice with 33
mg/liter methanol and 651 mg/liter ethanol (20/1 ratio) (45). The range
for grapefruit juices are similar, ranging from 0.2 mg methanol/liter27
to 43 mg methanol/liter (27). The lowest ratio of any food item was
found in canned grapefruit sections with 50-70 mg/liter methanol and
200-400 mg/liter ethanol27, thus averaging six molecules ethanol for
every molecule of methanol.

  This high ethanol to methanol ratio, even at these low ethanol
concentrations, may have some protective effect. As stated previously,
ethanol slows the rate of methanol's conversion to formaldehyde and
formate allowing the body time to excrete methanol in the breath and
urine. Inhibition is seen in vitro even when the concentration of ethyl
alcohol was only 1/16th that of methanol62. The inhibitory effect is a
linear function of the log of the ethyl alcohol concentration, with a
72% inhibition rate at only a 0.01 molar concentration of ethanol (2).
Therefore if a liter of a high methanol content orange juice is
consumed, with 33 mg/liter of methanol and a 20/1 ration of
ethanol/methanol, only one molecule of methanol in 180 will be
metabolized into dangerous metabolites until the majority of the ethanol
has been cleared from the bloodstream. If a similar amount of methanol
equivalent from aspartame were consumed, there would be no competition
(46).

  Another factor reducing the potential danger associated with methanol
from natural juices is that they have an average caloric density of 500
Kcal/liter and high Osmolality which places very definite limits to
their consumption level and rate.

  Data obtained in a Department of Agriculture survey of the food intake
of a statistically sampled group of over 17,000 consumers nationwide
(1), indicate that the 17.6% of the population that consume orange juice
daily take in an average of 185.5 gm of that juice. These statistics
indicate that 1.1% of the population consume an average of 173.9 gm of
grapefruit juice while only 1.8% drink approximately 201 gm of tomato
juice daily. Table 1 shows that under normal conditions these
individuals would only be expected to consume between 1 and 7 mg of
methanol a day from these sources. Even if an individual consumed two
juices in the same day or a more exotic juice such as black currant,
there would still be some protection afforded by the ethanol present in
these natural juices. Consumption of aspartame sweetened drinks at
levels commonly used to replace lost fluid during exercise yields
methanol intake between 15 and 100 times these normal intakes (Table 1).
This is comparable to that of "winos" but without the metabolic reprieve
afforded by ethanol. An alcoholic consuming 1500 calories a day from
alcoholic sources alone may consume between 0 and 600 mg of methanol
each day depending on his choice of beverages (Table 1).

  The consumption of aspartame sweetened soft drinks or other beverages
in not limited by either calories or Osmolality, and can equal the daily
water loss of an individual (which for active people in a state like
Arizona can exceed 5 liters). The resultant daily methanol intake might
then rise to unprecedented levels. Methanol is a cumulative toxin (8)
and for some clinical manifestations it may be a human-specific toxin.

  Conclusion

  Simply because methanol is found "naturally" in foods, we can not
dismiss the need for carefully documented safety testing in appropriate
animal models before allowing a dramatic increase in its consumption.

  We know nothing of the mutagenic, teratogenic or carcinogenic effect
of methyl alcohol on man or mammal (55,59). Yet, if predictions are
correct (5) it won't be long before an additional 2,000,000 pound of it
will be added to the food supply yearly (53).

  Must this, then, constitute our test of its safety?

  References

  1. Agricultural Research Service, U.S. Department of Agriculture,
Portion sizes and days intakes of selected foods, ARS-NE-67 (1975).

  2. Bartlett, G.R., Inhibition of Methanol Oxidation by Ethanol in the
Rat.Am. J. Physiol., 163:619-621 (1950).

  3. Braverman, J.B.S. and Lifshitz, A., Pectin Hydrolysis in Certain
Fruits During Alcoholic Fermentation. Food Tech., 356-358, July, (1957).

  4. Browning, E., Toxicity and Metabolism of Industrial Solvents, New
York: Elsevier Publishing Company, (1965).

  5. Bylinsky, G., The Battle for America's Sweet Tooth. Fortune, 28-32,
July (1982).

  6. Campbell, L.A., Palmer G.H., Pectin in Topics in Dietary Fiber
Research. Edited spiller, G.A. and Amen, R.J. Plenum Press, NY (1978).

  7. Casey,J.C., Self, R. and Swain, T., Origin of Methanol and Dimethyl
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  8. Cleland, J.G. and Kingsbury, G.L., Multimedia Environmental Goals
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600/7-77-136b, E-28, November 1977.

  9. Code of Federal Regulations 21 subpart C, Section 173.250.

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  11. DeCostro, F., et al., Clinical Toxicology Manual. St. Louis,
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  12. Dreisback, R.H., Handbook of Poisoning. 11th ed. Los Altos, CA:
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  13. Food and Drug Administration, Denial of Requests for Hearing.
Docket Nos. 75F-0355, 4160-01 (1984).

  14. Food and Nutrition Board: Recommended Dietary Allowances, 9th Ed.,
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  15. Francot, P. and Geoffroy, P., LeMethanol dans les jus de fruits,
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  16. Geokas, Michael C., Ethanol and the Pancreas. Med. Clin. N. Am.,
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