[Federal Register Volume 61, Number 178 (Thursday, September 12, 1996)]
[Proposed Rules]
[Pages 48102-48110]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-23159]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
21 CFR Part 101
[Docket No. 96N-0244]
Food Labeling; Declaration of Free Glutamate in Food
AGENCY: Food and Drug Administration, HHS.
ACTION: Advance notice of proposed rulemaking.
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SUMMARY: The Food and Drug Administration (FDA) is considering
establishing requirements for label information about the free
glutamate content of foods. The recent finding of the Federation of
American Societies for Experimental Biology (FASEB) that oral ingestion
of 3 or more grams (g) of monosodium glutamate (MSG) without food can
cause adverse reactions in certain otherwise healthy individuals has
prompted the agency to consider what action is necessary to protect
consumers from inadvertently ingesting levels of MSG or other forms of
free glutamate that could cause an adverse reaction. Thus, the agency
seeks public comment on whether additional labeling requirements are
necessary to protect glutamate-intolerant consumers from adverse
reactions, and, if so, how such labeling requirements should be
implemented. The agency also solicits comment on establishing formal
criteria for the use of claims about the absence of MSG to ensure that
labels bearing such claims are not misleading. The agency solicits
comment on whether such criteria should be based on a defined threshold
level of free glutamate in a finished food, on the ingredients used in
the food, or both.
[[Page 48103]]
DATES: Written comments by November 12, 1996.
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23,
Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT: Felicia B. Satchell, Center for Food
Safety and Applied Nutrition (HFS-158), Food and Drug Administration,
200 C St. SW., Washington, DC 20204, 202-205-5099.
SUPPLEMENTARY INFORMATION:
I. Background
A. Introduction
Glutamic acid, one of the amino acids found in nature, is a
building block of virtually all proteins and is a normal component of
the human body. In the human body and in most foods, glutamic acid
exists primarily in its salt form, glutamate. Glutamate is a naturally
occurring component of many foods, including tomatoes, cheese, meat,
mushrooms, and milk. ``Free'' glutamate is glutamate that is not
incorporated into a protein; ``bound'' glutamate is glutamate that is a
component of an intact protein. Meat and milk contain primarily bound
glutamate, while tomatoes, mushrooms, and certain cheeses contain, in
addition to bound glutamate, relatively high levels of free glutamate.
It is the free form of glutamate that has been shown to have
flavor-enhancing properties in food. As noted previously, some foods
contain relatively high levels of naturally occurring free glutamate.
Free glutamate may be introduced into foods as a component of various
food ingredients, such as tomato sauce and hydrolyzed protein products,
or it may be added in one of its various salt forms, such as MSG.
MSG is the most commonly used form of free glutamate added to food
for flavor-enhancing purposes. It is a white, practically odorless,
free-flowing crystalline powder (Ref. 1), similar in appearance to salt
or sugar. MSG has been used for many years as a flavor enhancer for a
variety of foods prepared in homes and restaurants and by food
processors. MSG is manufactured commercially by a fermentation process
using starch, beet sugar, cane sugar, or molasses. The American food
processing industry has used MSG widely since the late 1940's (Ref. 2),
and consumption in the United States is estimated to be 28,000 tons per
year. As a food ingredient, MSG is used to enhance the flavor of meat,
poultry, vegetables, and many processed foods. MSG is described in 21
CFR 182.1 as an example of a common food ingredient that is generally
recognized as safe (GRAS) under section 201(s) of the Federal Food,
Drug, and Cosmetic Act (the act) (21 U.S.C. 321(s)). When used as an
ingredient in a food, MSG must be declared in the ingredient statement
by its common or usual name, in accordance with section 403(i) of the
act (21 U.S.C. 343(i)) and 21 CFR part 101. Thus, ``monosodium
glutamate'' must appear in the ingredient list of any food to which MSG
has been added (21 CFR 101.22(h)(5)). This is true even when MSG has
been added indirectly as part of another ingredient to which MSG has
been added (e.g., a spice blend that includes MSG).
While MSG is the most well-known and widely used form of free
glutamate used to enhance the flavor of foods, other salts of free
glutamate, such as monopotassium glutamate and monoammonium glutamate
also have flavor-enhancing properties. GRAS uses of glutamic acid,
glutamic acid hydrochloride, monoammonium glutamate, and monopotassium
glutamate are codified in 21 CFR 182.1045, 182.1047, 182.1500, and
182.1516, respectively. Like MSG, these substances must be declared in
the ingredient statement of any food to which they are added.
Free glutamate occurs naturally in various foods and in food
substances that are used as ingredients in finished foods, or it can be
produced by hydrolysis of proteins; in such cases, the presence of free
glutamate in the food is not required to be declared on the label under
existing regulations. Naturally occurring free glutamate is not
required to be declared in the ingredient statement because it is not
an added ingredient; rather, it is a natural constituent of the food,
like protein or a vitamin. Similarly, when a food that contains
naturally occurring free glutamate is used as an ingredient in another
food, the free glutamate is not required to be declared in the
ingredient statement of the finished food. Rather, the ingredient
containing the free glutamate is declared in the ingredient statement
by its common or usual name. The principle that it is the ingredients
and not the constituents of a food that must be declared also applies
when a food that contains free glutamate produced by protein hydrolysis
is used as an ingredient in another food. In that situation too, the
glutamate-containing ingredient must be declared in the ingredient
statement of the finished food, but free glutamate need not be declared
as an ingredient. Because the average consumer is not aware that
ingredients like hydrolyzed soy protein, autolyzed yeast extract,
tomato paste, and parmesan cheese contain free glutamate or that free
glutamate is essentially equivalent to MSG, declaration of these
ingredients by their common or usual names does not indicate to the
consumer that an MSG-like substance is present in the food.
A number of consumers, particularly consumers who report adverse
reactions to MSG, have stated to FDA (Ref. 3) their belief that
manufacturers use ingredients such as hydrolyzed proteins and autolyzed
yeast extracts for the express purpose of adding free glutamate to a
food while hiding its presence. These consumers report the same types
of adverse reactions to foods containing hydrolyzed proteins, autolyzed
yeast extracts, and forms of ``manufactured'' glutamate (other than
MSG) that they experience when they inadvertently consume foods that
have MSG declared in the ingredient list. Consequently, FDA has
received numerous requests that labels of all foods containing these
ingredients be required to declare the presence of free glutamate in
the finished food, on the ground that free glutamate presents a health
concern to consumers. Some consumers have also requested that FDA
require that the amount of free glutamate be declared on the label.
Until recently, the agency's response has been that the scientific
literature does not provide a public health basis on which to impose
special labeling requirements for such ingredients or for foods that
contain free glutamate. However, in light of the recent findings of the
Life Sciences Research Office (LSRO) of FASEB, the agency is
reconsidering the need for labeling to inform individuals who
experience adverse reactions to glutamate about its presence in a food.
(The agency notes that in the Federal Register of January 6, 1993 (58
FR 2950), it proposed to require the term ``(contains glutamate)'' as
part of the common or usual name for autolyzed yeast extracts and
highly hydrolyzed proteins. That proposal was not based on any health
concern regarding the use of these ingredients in food; therefore, the
comments to that proposal and the agency's decision with respect to
those comments will not be addressed in this document.)
B. Previous Safety Reviews
Until the recent findings of the FASEB report (discussed in section
I.C. of this document) that a subgroup of otherwise healthy individuals
experiences a complex of symptoms following ingestion of 3 or more (g)
of MSG without food, FDA relied on
[[Page 48104]]
previous safety review studies in deciding that special labeling for
free-glutamate-containing (hereinafter referred to as ``glutamate-
containing'') foods was not warranted. These studies indicated that
while anecdotal reports of adverse reactions to MSG and other
glutamate-containing ingredients existed, there were no verifiable
scientific data establishing that the levels of these ingredients used
in the food supply could cause adverse reactions in the general
population. Historically, the agency has not issued labeling
requirements on the basis of anecdotal reports alone because such
reports do not by themselves establish a cause-and-effect relationship
between the suspected substance and the occurrence of an adverse
reaction.
MSG and other glutamate-containing ingredients have been the
subject of numerous safety reviews during the past decade. In 1969,
largely as a result of a recommendation by the White House Conference
on Food, Nutrition and Health, FDA proceeded to reevaluate the safety
of all GRAS substances for food use. The Select Committee on GRAS
Substances (SCOGS), convened by FASEB in 1972 under a contract with
FDA, independently reviewed the health aspects of MSG and of glutamate-
containing protein hydrolysates in 1978 and 1980 (Refs. 4, 5, 6, and
7). Although protein hydrolysates are not listed as GRAS food
ingredients by regulation, they are described as GRAS in a number of
FDA opinion letters (Refs. 8, 9, 10, and 11). SCOGS concluded that MSG
and hydrolyzed proteins were safe for the general population at then-
current levels of use but recommended additional evaluation to
determine their safety at significantly higher levels of consumption.
In 1986, FDA's Advisory Committee on Hypersensitivity to Food
Constituents (Ref. 12) concluded that MSG posed no threat to the
general public but that reactions of brief duration might occur in some
people. Other reports gave similar findings. A 1991 report by the
European Community's (EC) Scientific Committee for Foods (Ref. 13)
reaffirmed the safety of MSG and other forms of free glutamate and
classified the ``acceptable daily intake'' for MSG as ``not
specified,'' the most favorable designation for a food ingredient. In
addition, the EC committee said, ``infants, including prematures, have
been shown to metabolize glutamate as efficiently as adults and,
therefore, do not display any special susceptibility to elevated oral
intakes of glutamate.''
A 1992 report from the Council on Scientific Affairs of the
American Medical Association (Ref. 14) stated that glutamate in any
form has not been shown to be a ``significant health hazard.'' Also,
the 1987 Joint Expert Committee on Food Additives of the United Nations
Food and Agriculture Organization and the World Health Organization
(Ref. 15) placed MSG and other glutamate salts in the safest category
of food ingredients.
Although the general consensus of the many safety reviews that have
been done on the use of MSG and other glutamate-containing ingredients
in foods is that they are safe for the general population, the use of
these ingredients has been very controversial. FDA has received many
anecdotal reports of adverse reactions following ingestion of
glutamate-containing foods. Between 1980 and 1995, the Adverse Reaction
Monitoring System in FDA's Center for Food Safety and Applied Nutrition
received 661 reports of complaints about adverse reactions to MSG (Ref.
16). Headache was the most frequently reported symptom. However, other
symptoms, such as a ``burning sensation'' on the back of the neck,
forearms, and chest, facial pressure or tightness, neck and chest pain,
palpitations, numbness, nausea, and vomiting, were also reported. These
symptoms were transient, typically beginning within 25 minutes after
consumption of MSG or of a glutamate-containing food and subsiding
within about 2 hours. Initially many of these symptoms became known
popularly as ``Chinese Restaurant Syndrome.'' As discussed in section
I.C. of this document, FASEB refers to these symptoms collectively as
the ``MSG symptom complex.''
C. The FASEB Report
Because of the agency's concern regarding the continued reports of
adverse reactions to MSG and other glutamate-containing ingredients and
because of the expanding base of scientific knowledge on the role of
glutamate in brain function, FDA decided that an up-to-date review of
the safety of MSG and other glutamate-containing ingredients was
warranted. Thus, as part of its ongoing evaluation of GRAS ingredients
and in response to the concerns raised by consumers, FDA contracted
with FASEB in 1992 to do an up-to-date scientific safety review of the
effects of the use of MSG and hydrolyzed protein products as food
ingredients. The agency announced the study in the Federal Register of
December 4, 1992 (57 FR 57467). As discussed in that document, the
objectives of the review were to: (1) Determine whether MSG and
hydrolyzed protein products, as used in the American food supply,
contribute to the presentation of a complex of symptoms (initially
described as the Chinese Restaurant Syndrome) after oral ingestion of
levels up to or beyond 5 g per eating occasion (i.e., a meal or snack),
and/or the elicitation of other reactions, including more serious
adverse reactions that have been reported to occur following ingestion
of 25 to 100 milligrams per eating occasion; (2) to determine whether
MSG and hydrolyzed protein products, as used in the American food
supply, have the potential to contribute to brain lesions in neonatal
or adult nonhuman primates and whether there is any risk to humans
ingesting dietary MSG; (3) to assess whether hormones are released from
the pituitary of nonhuman primates following ingestion of MSG or
hydrolyzed protein products and whether any comparable risk to humans
ingesting food containing these substances exists; and (4) to define
the metabolic basis that might underlie any adverse reactions to MSG
and hydrolyzed protein products.
FASEB convened an ad hoc expert panel to perform a comprehensive
review of the scientific literature and adverse report submissions to
both FDA and LSRO. The expert panel also considered oral and written
testimony received at a 2-day open meeting held in 1993. The expert
panel used a weight of evidence approach in reaching its conclusions
about the evidence of adverse effects of MSG. In other words, the
expert panel analyzed the data by considering the totality of the
scientific evidence in a given area rather than weighing one
interpretation against another.
The expert panel reported its findings to FASEB, which reviewed the
expert panel's work and prepared a report entitled ``Analysis of
Adverse Reactions to Monosodium Glutamate (MSG)'' (Ref. 17). The FASEB
report was submitted to FDA on July 31, 1995. While FASEB found no
scientifically verifiable evidence of adverse effects in most
individuals exposed to high levels of MSG, it concluded that there is
sufficient documentation to define an acute, temporary, and self-
limiting ``MSG symptom complex'' in a subgroup of the population. The
symptoms characteristic of the complex include: (1) A burning sensation
of the back of the neck, forearms, and chest; (2) facial pressure or
tightness; (3) chest pain; (4) headache; (5) nausea; (6) upper body
tingling and weakness; (7) palpitation; (8) numbness in the back of
neck, arms and back; (9) bronchospasm, i.e., constriction of the
bronchial tubes
[[Page 48105]]
resulting in difficulty in breathing (observed in asthmatics only); and
(10) drowsiness. These symptoms were judged to be related to the amount
of MSG consumed and whether the MSG was consumed with or without food.
FASEB identified this group of symptoms as the ``MSG symptom complex,''
stating that the previously used term, ``Chinese restaurant syndrome,''
was pejorative and did not reflect the extent or nature of the symptoms
that have been associated with the myriad of exposure scenarios. FASEB
concluded that ``Based on scientifically verifiable evidence, there is
a subgroup of presumably healthy individuals within the general
population that responds, generally within one hour of exposure, with
manifestations of the MSG Symptom Complex to an oral bolus [dose] of
MSG 3 g in the absence of food.''
FASEB also identified a subgroup of asthmatics reported to respond
to oral doses of MSG with bronchospasm. The study conducted by Allen,
Delohery, and Baker (Ref. 18) described severe bronchospasm in
individuals with unstable asthmatic conditions in conjunction with
symptoms of the MSG symptom complex following an oral dose of MSG. In
addition, the study reported that some asthmatic subject experienced a
6 to 12 hour delayed bronchospasm without other MSG-related symptoms.
While FASEB recognized and described limitations in the study design
used by Allen, et al., it concluded that the study was a reasonably
well-designed scientific oral dose study in asthmatic subjects, and
that the study provided evidence to support the existence of a subgroup
of asthmatic responders to MSG.
With regard to hydrolyzed proteins, FASEB identified no scientific
reports of glutamate-related adverse effects of ingesting protein
hydrolysates, whether microbial, vegetable, or animal in origin.
Protein hydrolysates are used at very low levels, typically
constituting only a small percentage (less than 1 percent) of a
finished food.
Because of glutamate's role as a stimulatory neurotransmitter in
the brain, the scientific community has speculated about the potential
influence of dietary glutamate on brain glutamate metabolism and the
potential role of dietary glutamate in provoking or exacerbating long-
term illnesses. At FDA's request, FASEB reviewed the scientific
literature on these issues. Although FASEB acknowledged the neurotoxic
potential of glutamate produced in the body (as opposed to glutamate
consumed in food), it found no studies or corroborating evidence
linking adverse effects associated with consuming free glutamate in
food to changes in brain function or to levels of glutamate in the
bloodstream. Consequently, FASEB concluded that no evidence exists to
support a role for dietary MSG or other forms of free glutamate
consumed in food in causing or exacerbating serious, long-term medical
problems resulting from degenerative nerve cell damage, such as
Alzheimer's disease, Huntington's chorea, or amyotrophic lateral
sclerosis, or to any other long-term or chronic illness. However, FASEB
recommended that future efforts to explain reported adverse effects
from ingested MSG be designed to test potential relationships between
dietary glutamate and the physiological functions of the central
nervous system.
FASEB also reviewed the chemical characteristics of various forms
of free glutamate to determine if there was some structural or chemical
difference in free glutamate occurring in the form of MSG or hydrolyzed
protein products, as compared to free glutamate that naturally occurs
in foods. FDA asked FASEB to include this issue in its review because
of the contention by some consumers that manufactured forms of
glutamate, such as MSG and hydrolyzed protein products, are in some way
different from naturally occurring glutamates, and that the
manufactured forms of glutamate are the only forms that trigger adverse
reactions.
Free glutamate can exist in two possible stereoisomeric forms: D-
glutamate and L-glutamate. L-glutamate is the predominant natural form
and the only form with flavor-enhancing activity. FASEB concluded that
MSG symptom complex reactions are related to L-glutamate exposure and
that the chemical nature of L-glutamate is the same regardless of the
source, i.e., whether manufactured or naturally occurring in the food.
Thus, FASEB found no evidence to support the contention that adverse
reactions occur with manufactured but not naturally occurring
glutamate.
FASEB further concluded that with regard to determining glutamate
levels and assessing risk from consumption of specific foods, a clear
distinction must be made between free glutamate and glutamate as a
component of protein (i.e., bound glutamate). Free glutamate is readily
available for use in the body, whereas bound glutamate becomes
available to body tissues more slowly, as the intestines chemically
break down foodstuffs. FASEB also noted that the presence of food, as
when MSG is consumed as part of a meal, attenuates the rise in blood
glutamate levels and perhaps the effect, at least with regard to the
potential for any direct central nervous system effect. However, FASEB
was unable to identify any studies that have effectively compared blood
glutamate levels between responders (i.e., persons who experience
adverse reactions following exposure to MSG) and nonresponders, or any
studies in which responders have been given a dose of MSG with a meal
or 20 to 30 minutes before a meal.
FDA has reviewed the findings and conclusions contained in the
FASEB report (Ref. 19). Based on FASEB's findings, FDA has tentatively
concluded that requirements for label information about glutamate
content may be warranted under certain conditions.
II. The Agency's Response
FASEB's conclusion that oral ingestion of 3 or more grams of MSG
without food can cause adverse reactions in certain otherwise healthy
individuals has prompted the agency to consider what action is
necessary to protect these consumers from inadvertently ingesting
levels of free glutamate that could trigger an adverse reaction. The
agency believes that it may be appropriate to establish labeling
requirements to alert free-glutamate-intolerant (hereinafter referred
to as ``glutamate-intolerant'') consumers to the presence of free
glutamate in a food.
The agency has carefully evaluated FASEB's findings and has reached
several tentative conclusions regarding the basis on which any labeling
policy to alert glutamate-intolerant consumers should be established.
A. Total Free Glutamate
Based on FASEB's findings that it is the free glutamate component
of MSG that appears to be linked to the occurrence of the MSG symptom
complex, that free glutamate is the same chemically in both its natural
and manufactured forms, and that free glutamate has the same function
regardless of source, i.e., free glutamate in MSG functions the same as
free glutamate in hydrolyzed proteins or tomato products, the agency
tentatively finds that any labeling policy it establishes should be
based on the total amount of free glutamate in a serving of food,
rather than on the number or kind of glutamate-containing ingredients
in the food.
FDA has received correspondence suggesting that adverse reactions
result only from exposure to manufactured free glutamate in food (Ref.
3). Based on FASEB's findings, the agency rejects this view. As
previously discussed,
[[Page 48106]]
FASEB reported that all free glutamate found in food is the same
regardless of the source. Further, in examining the scientific reports
relating to physiological mechanisms of action, FASEB found no evidence
indicating that manufactured free glutamate functions differently in
the body than free glutamate naturally occurring in foods. The agency
agrees with FASEB that all forms of free glutamate are chemically and
functionally the same. Moreover, the agency notes that the available
analytical methodology measures the total amount of free glutamate in a
finished food and does not distinguish among free glutamate occurring
in the form of MSG, as a constituent of ingredients such as hydrolyzed
proteins, or as a natural constituent of food such as cheese,
mushrooms, or meat. Accordingly, the agency tentatively finds that any
labeling requirement for glutamate-containing foods should apply to
foods that contain free glutamate from any source.
B. Food Matrix
Although FASEB noted that the presence of food may attenuate the
rise of blood glutamate levels, the FASEB report cited no scientific
evidence establishing a relationship between the occurrence of MSG
symptom complex reactions and metabolic responses to ingestion of MSG,
such as changes in blood glutamate levels. The agency requests data
describing the effect of the food matrix (i.e., the food in which free
glutamate is present or with which it is eaten) on the occurrence of
the MSG symptom complex. If the food matrix does have an effect, does
the effect vary depending on the type of food?
In the absence of sound scientific data demonstrating that the food
matrix reduces the risk or severity of adverse effects following
ingestion of free glutamate, the agency's likely approach would be to
assume that the food matrix has no predictable mitigating effect on the
occurrence of the MSG symptom complex and to develop a labeling policy
based on the level of free glutamate reported to cause reactions when
consumed without food. Because the agency does not yet have such data,
this assumption is adopted for purposes of the preliminary discussion
in this document.
C. Materiality
Section 403(a) of the act (21 U.S.C. 343(a)) states that a food is
misbranded if its labeling is false or misleading in any particular.
Under section 201(n) of the act, labeling is misleading if it ``fails
to reveal facts material * * * with respect to consequences which may
result from the use of the article to which the labeling or advertising
relates under the conditions of use prescribed in the labeling * * * or
under such conditions of use as are customary or usual.'' Thus, a food
label is misleading if it does not disclose consequences that may
result from consumption of the food.
The agency believes that information on the presence of free
glutamate in a food becomes a material fact for the glutamate-
intolerant consumer in the decision to purchase a food (and in the
subsequent use of the food) when free glutamate is present at a level
such that a glutamate-intolerant person who consumes the food alone or
as part of a meal that includes other glutamate-containing foods may
suffer an adverse reaction. The presence of free glutamate below this
level is not material because it would not cause a reaction or
contribute significantly toward a total intake of free glutamate that
might cause a reaction. Moreover, special glutamate labeling on
products that contain levels of free glutamate below the material level
could cause the label statement to lose its significance for glutamate-
intolerant consumers, especially if such labeling appeared on products
previously consumed by such consumers without subsequent occurrence of
any adverse reaction.
The level shown to elicit adverse reactions in glutamate-intolerant
individuals is 3 g of MSG, according to the FASEB report. Based on this
data, the agency tentatively finds that the presence of free glutamate
in a serving of the food in an amount such that consumption of the food
as part of a meal may expose the consumer to the equivalent of 3 g of
MSG is a material fact under section 201(n) of the act. Using a
conversion factor of 0.787 to correct for the inactive portion of the
MSG molecule (MSG consists of free glutamate plus sodium and water), 3
g of MSG converts to approximately 2.4 g of free glutamate.
Accordingly, an effective labeling policy should assist glutamate-
intolerant consumers in restricting their consumption of free glutamate
during a meal or snack to levels below 2.4 g.
As discussed in section I. of this document, FASEB identified a
subgroup of asthmatics reported to respond to oral doses of MSG at
levels of 0.5 to 2.5 g. The agency believes that the limitations of the
Allen study cited by FASEB in reaching this conclusion are
considerable, however (Ref. 19). For example, the study design
included: (1) A 5-day pretest diet excluding chemicals known to provoke
asthma (not otherwise defined), but lacked data with regard to patient
compliance with the pretest diet; (2) ingestion of unidentified
substances other than MSG; (3) limited placebo-control testing; and,
most importantly, (4) the withdrawal of asthma medication that could
have prevented or delayed an asthmatic response. Because of the
questions raised by the study design and the limited data in this area,
FDA's current view is that a cause-and-effect relationship has not been
established between exposure to MSG at levels of 0.5 to 2.5 g and
adverse reactions in this subgroup of asthmatics. The agency requests
comments on this aspect of the FASEB report, as well as any new data
demonstrating a relationship between exposure to free glutamate at
levels below 2.4 g (3 g of MSG) and adverse reactions in asthmatics. If
such data are received, FDA will be better able to evaluate the need
for a labeling policy to enable glutamate-intolerant asthmatics to
protect themselves from adverse reactions.
FDA's preliminary view is that a policy requiring glutamate
labeling should be based on the amount of free glutamate in a serving
of a food. Foods are labeled individually to reflect the nutrient
content and other characteristics of the particular food. Because a
food's contribution to the diet is based on an individual serving of
the food, current regulations require foods to be labeled with
nutrition information on a per-serving basis. Since the regulations
implementing the Nutrition Labeling and Education Act (Pub. L. 101-445)
became effective in 1994, consumers have become adept at using label
information to monitor their intake of certain nutrients (Ref. 20). A
glutamate labeling policy based on the amount of free glutamate in a
serving of a food would be consistent with current labeling
regulations, and FDA tentatively finds that such a policy would be
useful to consumers who wish to avoid intake of free glutamate at
levels that may cause an adverse reaction.
D. Labeling Threshold Approach
Applying these principles, the question then becomes how to
calculate an appropriate labeling threshold, i.e., the level of free
glutamate in a serving of an individual food that should trigger a
labeling requirement because consumption of the food as part of a meal
that may include other glutamate-containing foods could result in
overall intake of free glutamate at levels that have been demonstrated
to cause an adverse reaction. That is, what is the appropriate
mechanism to relate a total
[[Page 48107]]
intake of 2.4 g of free glutamate (from all servings of foods consumed
at the meal) to the contribution of an individual food?
One possible approach is to assume that the average daily
consumption of a U.S. consumer is 20 servings per day, spread over
approximately 3 meals and a snack. A snack is considered roughly two
servings and a meal five to six servings. (The agency used a similar
approach in determining disclosure levels for nutrient content claims
and disqualifying levels for health claims. (56 FR 60426, 56 FR 60543-
60544, 58 FR 2492, and 59 FR 24239)). Assuming that a meal consists of
approximately six servings, the glutamate-intolerant consumer would be
at risk if the total amount of free glutamate from all six servings in
the meal were equal to or greater than 2.4 g. Spreading this amount
equally over each of the six servings would suggest that each serving
of food should contain no more than 0.4 g of free glutamate. Thus, one
approach could be to require any food containing 0.4 g or more free
glutamate per serving to bear a label statement about its free
glutamate content. Such labeling would alert the glutamate-intolerant
consumer to foods that contribute significant levels of free glutamate
to a meal. With such information, the consumer could avoid foods with
significant levels of free glutamate or, as an alternative, include
limited quantities of a labeled food in the meal while being careful
not to eat other glutamate-containing foods. Using 0.4 g as a labeling
threshold would require foods like tomato juice and some soup mixes and
canned soups to bear glutamate labeling (Ref. 21).
Although a labeling threshold or ``trigger'' of 0.4 g per serving
based on average consumption estimates would adequately protect most
glutamate-intolerant consumers, it might not be sufficient to protect
those whose food intake is in the high range, that is, at or above the
90th percentile. According to food consumption and food frequency
surveys (Refs. 22 and 23) conducted in the United States, intake at the
90th percentile for most commonly consumed foods is roughly 2 times the
mean intake for that food (Ref. 24). Thus, a high-intake consumer could
be exposed to levels close to 0.8 g from a single food if a regular-
size serving of the food contained just under 0.4 g of free glutamate.
In such a case, the food would not be required to bear a glutamate
content statement, yet the amount eaten by high-intake consumers would
contain a significant level of free glutamate. Taking into
consideration the number of products that may contain free glutamate
and the acute nature of the effects of free glutamate exposure for
certain individuals, the agency is concerned that a label trigger of
0.4 g would not sufficiently protect high-intake consumers. The agency
believes, therefore, that it is prudent to build in a safety factor to
ensure that high-intake consumers are adequately informed of any
potential risk.
Allowing for intakes up to twice the mean intake, to provide an
additional margin of safety, would result in a labeling threshold of
0.2 g free glutamate (0.4 divided by 2) per serving of food. If the
agency were to take this approach and require a glutamate label
statement for foods that contain 0.2 or more grams free glutamate per
serving, additional foods such as blue cheese, spaghetti sauce, and
some brands of soy sauce and tomato paste would be required to bear a
label statement about free glutamate content (Ref. 21).
FDA notes that the use of labeling thresholds is not new. Existing
regulations establish labeling thresholds for certain ingredients that
have been identified as causing adverse reactions either in sensitive
individuals or in the general population. These regulations require
special labeling for foods that exceed the labeling threshold. For
example, the statement ``Excess consumption may have a laxative
effect'' is required on foods that contain sorbitol when ``reasonably
foreseeable'' consumption of the food could result in a daily sorbitol
intake of 50 g or more (21 CFR 184.1835). To cite another example, the
label statement ``Sensitive individuals may experience a laxative
effect from excessive consumption of this product'' is required when a
single serving of a food contains more than 15 grams of polydextrose
(21 CFR 172.841). To the best of the agency's knowledge, the use of a
labeling threshold has worked well in protecting consumers from adverse
reactions caused by excessive consumption of sorbitol and polydextrose.
E. Request for Comments
FDA is soliciting comments on all aspects of this advance notice of
proposed rulemaking (ANPRM), and specifically requests comments on the
following:
1. The agency invites comments on whether additional labeling
requirements should be established to protect glutamate-intolerant
consumers from adverse reactions. The agency also solicits comments on
the effectiveness of the regulatory approach described previously, as
well as suggestions for other approaches that would adequately inform
and assist glutamate-intolerant consumers to avoid exposure to levels
of free glutamate that might cause a reaction. Suggestions for other
approaches should include data or other information to substantiate the
effectiveness of the approach. In particular, the agency solicits
comments on whether the labeling threshold should be set higher or
lower than 0.2 g free glutamate per serving, and on the costs and
benefits of labeling policies using different possible labeling
thresholds. The agency notes that regulations based on this ANPRM may
have a significant impact on a substantial number of small entities.
Therefore, the agency particularly requests information on the costs to
small businesses of alternative MSG labeling policies and on policy
options that would reduce the burden on small businesses while meeting
the objectives of MSG labeling. Recognizing that foods would have to be
chemically analyzed to determine the free glutamate content and that
labels would have to be changed for some foods, the agency solicits
data and comments on the economic impact associated with various
labeling policies.
2. The agency solicits data on the levels of glutamate in foods to
assist it in determining how many and what kinds of foods would be
affected by various regulatory approaches.
3. The agency also solicits comments on the advantages or
disadvantages of a simple label statement that the food contains free
glutamate, as compared to a quantitative statement of the amount of
free glutamate in a serving of the food either in absolute terms (i.e.,
g) or as a percentage of the intake level that might lead to adverse
reactions in some consumers. As a preliminary matter, FDA's view is
that quantitative labeling is not necessarily any more useful than a
general label statement alerting the glutamate-intolerant consumer to
the presence of free glutamate in the food when the level is
significant. The agency notes that because almost all foods contain
trace levels of free glutamate, quantitative labeling for all foods
with detectable levels of free glutamate might cause confusion among
glutamate-intolerant consumers about which foods could be consumed
without risking a reaction. Consumers might unnecessarily limit their
food choices by assuming that they should not eat any food labeled to
contain any amount of free glutamate, however small. FDA's preliminary
view is that, if quantitative labeling is required, a labeling
threshold should be established to prevent this problem. The agency
solicits comments on this view and on whether the optimal threshold for
quantitative free glutamate labeling
[[Page 48108]]
would be the same as the optimal threshold for a label statement that
the food contains free glutamate.
4. Finally, the agency solicits comments on the following questions
regarding the content, wording, and placement of labeling for
glutamate-containing foods, and on any other aspects of such labeling:
(a) What information should be included in labeling for glutamate-
containing foods? How should any required label statement be worded?
Should the scientifically accurate term ``free glutamate'' be used in
such labeling, or should the term ``MSG'' be used for all forms of free
glutamate because consumers are more familiar with it?
(b) Should a label statement such as ``contains free glutamate'' be
included in the ingredient list because consumers traditionally use the
ingredient list to determine if the food contains ingredients they wish
to avoid? Alternatively, should such a label statement be placed
adjacent to the ingredient list or elsewhere on the information panel,
or should the label statement be placed on the principal display panel?
Suggestions for placement of the label statement should include the
comment's rationale for choosing one location over another.
(c) Is a separate label statement about free glutamate content
necessary when MSG is an ingredient in the food and is therefore
declared in the ingredient list? Current information in the agency's
possession suggests that glutamate-intolerant consumers already
identify and avoid foods that declare MSG as an ingredient, although
they often fail to recognize the presence of free glutamate when it
occurs in forms other than MSG (Ref. 3). Thus, the agency solicits
comments on the need for a statement about free glutamate content in
foods that contain MSG as a declared ingredient.
III. The ``No MSG'' Labeling Policy
A. Current Label Claims
The controversy over the use and safety of MSG in foods has
prompted some food manufacturers to make label claims such as ``No
MSG'' or ``No added MSG'' when MSG is not used as an ingredient in the
food. Several manufacturers have opted to reformulate their products to
remove MSG as an ingredient, or to substitute for MSG other ingredients
that have similar flavor-enhancing properties. Many of these
reformulated foods bear label claims about the absence of MSG. In some
cases manufacturers replace MSG with ingredients like hydrolyzed
proteins, autolyzed yeast extracts, or other flavor-enhancing
ingredients that contain substantial amounts of free glutamate.
Based on correspondence submitted to the agency and arguments
raised in a citizen petition submitted on behalf of Jack L. Samuels,
Adrienne Samuels, John Olney, et al., (Docket No. 94P-0444), FDA
recognizes that many consumers, especially those who report having
adverse reactions to MSG, refer to all forms of manufactured glutamate
as MSG. As previously discussed, the scientific evidence does not
support the assertion that manufactured free glutamate functions
differently in the body than naturally occurring free glutamate.
Moreover, even though FDA has attempted to clarify the distinction
between the ingredient monosodium glutamate (MSG) and other ingredients
that contain free glutamate in correspondence and other FDA documents,
such as FDA's Backgrounder on MSG (Ref. 25), consumers either do not
fully understand or do not acknowledge this distinction. Consequently,
consumers continue to use the term ``MSG'' to mean all forms of free
glutamate that are added to food. For example, FDA has received
numerous written and oral complaints (Ref. 3) charging manufacturers
with hiding the presence of ``MSG'' by declaring the substance under
other names such as ``flavorings,'' ``hydrolyzed protein,'' ``autolyzed
yeast extract,'' and similar terms.
FDA tentatively finds that consumers are likely to perceive a ``No
MSG'' or ``No added MSG'' claim on a label as indicating the absence of
all forms of free glutamate in the food. Such claims encourage
consumers wishing to avoid free glutamate to purchase a food by
representing the food as free of MSG. Moreover, manufacturers of
hydrolyzed proteins and other glutamate-containing ingredients often
promote them to manufacturers of finished foods as functional
substitutes for MSG that permit a ``clean'' ingredient statement and a
``No MSG'' claim on the label of the finished food. In this context,
``clean'' means an ingredient list that does not include ``monosodium
glutamate.'' Thus, while technically such foods bearing a claim about
the absence of MSG do not contain the ingredient monosodium glutamate,
they frequently contain levels of free glutamate that cause claims like
``No MSG'' and ``No added MSG'' to be misleading. Some manufacturers
attempt to evade the ingredient declaration requirement for MSG by
reformulating their products with MSG-containing ingredients (for
example, certain spice blends) that are added to the product in lieu of
MSG itself. They then modify the ingredient list on the product label
to delete MSG and replace it with a generic term such as ``spices.''
(As noted in section I. of this document, this practice violates
existing ingredient labeling requirements; when MSG is added to a food
as an ingredient of a spice blend, MSG must still be declared in the
ingredient statement by its common or usual name, monosodium
glutamate.) In some cases, these manufacturers also add a ``No MSG''
claim to the label.
A related problem is the use of claims such as ``No MSG'' and ``No
added MSG'' on foods that contain substantial amounts of naturally
occurring free glutamate, such as tomato paste and certain cheeses.
Although such foods do not contain MSG itself, they contain ingredients
with concentrations of free glutamate that function as flavor enhancers
like MSG. Because of their free glutamate content, these foods are as
likely to cause or contribute to an MSG symptom complex reaction as a
food that contains a comparable amount of MSG. A claim such as ``No
MSG'' is misleading because it implies that the food may be consumed by
glutamate-intolerant consumers without risk of a reaction.
A food that bears a false or misleading claim about the absence of
MSG is misbranded under section 403(a) of the act. FDA has repeatedly
advised consumers and industry that it considers such claims as ``No
MSG'' and ``No added MSG'' to be misleading when they are used on the
labels of foods made with ingredients that contain substantial levels
of free glutamate (Refs. 25, 26, and 27). FDA has authority to take
action against such misbranded foods under existing law, but because of
the proliferation of such claims on products made with ingredients that
contain substantial levels of free glutamate, the agency believes that
formal criteria would be useful to define more precisely the
circumstances under which labels bearing claims about the absence of
MSG are misleading. While such criteria are being developed, however,
FDA will continue to take regulatory action as appropriate against
false or patently misleading claims about the absence of MSG, such as
``No MSG'' claims on products made with MSG-containing ingredients,
hydrolyzed proteins, or autolyzed yeast extracts.
B. Approaches Under Consideration
The agency is considering a variety of approaches to address
misleading claims about the absence of MSG. As a
[[Page 48109]]
starting point, a food that contains MSG, or ingredients to which MSG
has been added, is misbranded if it bears a ``No MSG'' or similar
claim. Such claims are false and, therefore, their regulatory status
needs no further clarification. The discussion below concerns the
development of criteria to prevent misbranding because of misleading
``No MSG'' and ``No added MSG'' claims on foods that contain free
glutamate but to which MSG itself has not been added, directly or
indirectly.
1. Cutoff levels
One strategy the agency is considering involves establishing a
``cutoff level'' for claims about the absence of free glutamate. If the
finished food contains free glutamate above the cutoff level, a ``No
MSG'' or similar label statement would be prohibited. There are several
ways in which such a level could be defined:
a. Quantitation limit for free glutamate. One approach would be to
use the analytical limit of quantitation (LOQ) for free glutamate as
the cutoff level. The enzymatic procedure of Hattula and Wallin (Ref.
28), a commonly used, collaboratively studied analytical method for
determining free glutamate content, has an estimated quantitation limit
of 100 parts per million (ppm) (Ref. 29). Under this approach, any food
with a level of free glutamate above the LOQ, i.e., a level above 100
ppm using the Hattula and Wallin method, would be disqualified from
bearing a ``No MSG'' claim. However, because glutamate is ubiquitous in
the food supply and low levels of free glutamate typically occur in
many raw or minimally processed foods, using the LOQ as the cutoff
level would disqualify almost all foods from bearing a ``No MSG''
claim. For example, typical levels of free glutamate in canned peas and
canned corn are 320 ppm (.032 g) and 470 ppm (.047 g) respectively
(Ref. 30). Although these levels are lower than the level generally
associated with flavor-enhancing function (500 ppm) and lower than the
amount of free glutamate found in most foods containing monosodium
glutamate, hydrolyzed proteins, or yeast extracts, they are above the
LOQ of 100 ppm. Consequently, relying on a ``limit of quantitation''
criterion would disqualify foods like canned peas and canned corn from
bearing a ``No MSG'' claim.
b. Functional level. According to the scientific literature (Ref.
31), free glutamate has a flavor-enhancing effect at levels as low as
500 ppm. Using 500 ppm as the cutoff level for claims about the absence
of MSG would allow a ``No MSG'' label statement on most raw or
minimally processed foods that naturally contain free glutamate, while
prohibiting such claims on MSG substitutes like protein hydrolysates
and autolyzed yeast extracts. Under this approach, foods such as canned
peas and canned corn would be permitted to bear a ``No MSG'' claim.
However, tomato sauce and fresh tomatoes, because of their relatively
high natural free glutamate content, would be prohibited from bearing
such a claim, as would parmesan cheese.
c. Labeling threshold. As discussed in section II. of this
document, the agency is considering whether to require a label
statement about free glutamate content on foods that contain 0.2 g or
more free glutamate per serving. For consistency, the cutoff for claims
about the absence of MSG could be set at the same level. Under this
approach, a ``No MSG'' claim would be permitted on foods like canned
peas and canned corn. However, bacon flavored toppings made from
hydrolyzed vegetable protein would also qualify to bear a ``No MSG''
claim because the serving size for toppings is so small. Claims about
the absence of MSG would be prohibited on any food required to bear a
label statement about the presence of free glutamate.
The agency solicits comment on whether an approach based on a
cutoff level of free glutamate in the finished food should be adopted
to determine whether a food may bear a ``No MSG'' or ``No added MSG''
claim. Further, the agency solicits comment on whether such a cutoff
level should be: (a) The analytical limit of quantitation for free
glutamate; (b) the level at which free glutamate functions as a flavor
enhancer; (c) the level of free glutamate that would trigger a label
statement about the food's glutamate content; or (d) some other level.
2. Ingredients
The second approach the agency is considering would prohibit ``No
MSG'' and similar claims on foods made from ingredients that contain
substantial amounts of free glutamate. In the agency's opinion,
ingredients like hydrolyzed vegetable proteins, autolyzed yeast
extracts, soy sauce, parmesan cheese, and tomato paste contain enough
free glutamate to cause a ``No MSG'' label claim to be misleading. To
adopt this approach, the agency would have to define what constitutes a
``substantial'' amount of free glutamate in an ingredient. Should a
``substantial'' amount of free glutamate be defined as the amount
reported to have flavor-enhancing properties, i.e., 500 ppm (Ref. 31),
or in some other way?
Further, is an approach that prohibits a ``No MSG'' claim if an
ingredient in a food contains a ``substantial'' amount of free
glutamate equitable in all cases, or should the amount of an ingredient
added to a food also be considered in determining whether a claim is
misleading? For example, could ingredients like tomato paste or soy
protein isolate be added to a food in trace amounts without rendering a
``No MSG'' claim misleading?
3. Combination or Other Approaches
The agency also invites comments on possibilities for combining any
of the approaches described in this section to develop a comprehensive
labeling policy to ensure that ``No MSG'' claims are truthful and not
misleading. For example, would a labeling policy that allowed a ``No
MSG'' or similar claim only on foods that: (1) Contain no ingredients
that have a ``substantial'' amount of free glutamate, and (2) contain
levels of total free glutamate per serving below a cutoff level of 0.2
g, be more desirable than a policy that relied on one criterion alone?
This approach would permit claims about the absence of MSG on foods
like canned peas and canned corn, but prohibit such claims on foods
like bacon flavored toppings made with hydrolyzed protein and on foods
that have a relatively high natural free glutamate content, including
tomato sauce and parmesan cheese. Alternatively, is there another
combination of approaches that would be more effective in ensuring that
label claims about the absence of MSG are not misleading? Suggestions
for other approaches or combinations of approaches should include data
or other information to substantiate the effectiveness of the approach.
IV. References
The following references have been placed on display in the Dockets
Management Branch (address above) and may be seen by interested persons
between 9 a.m. and 4 p.m., Monday through Friday.
1. National Academy of Science, ``Food Chemicals Codex,'' 4 ed.,
1996, p. 260.
2. Taliaferro, P. T., ``Monosodium Glutamate and the Chinese
Restaurant Syndrome: A Review of Food Additive Safety,'' Journal of
Environmental Health, vol. 57, No. 10, pp. 8-12, 1995.
3. Satchell, F. B., Division of Programs and Enforcement Policy
(HFS-158), Center for Food Safety and Applied Nutrition, memorandum
to file: ``Consumer Correspondence to FDA Regarding the Use and
Labeling of MSG in Foods,'' July 3, 1996.
[[Page 48110]]
4. Select Committee on GRAS Substances, Life Sciences Research
Office, Federation of American Societies for Experimental Biology,
``Evaluation of the Health Aspects of Certain Glutamates as Food
Ingredients-Report 37a,'' (PB 283-475/AS), 1978.
5. Select Committee on GRAS Substances, Life Sciences Research
Office, Federation of American Societies for Experimental Biology,
``Evaluation of the Health Aspects of Protein Hydrolysates as Food
Ingredients- Report 37b,'' (PB 283-440/AS), 1978.
6. Select Committee on GRAS Substances, Life Sciences Research
Office, Federation of American Societies for Experimental Biology,
``Evaluation of the Health Aspects of Certain Glutamates as Food
Ingredients, Supplemental Review and Evaluation-Report 37a-Suppl.,''
(PB 178635), 1980.
7. Select Committee on GRAS Substances, Life Sciences Research
Office, Federation of American Societies for Experimental Biology,
``Evaluation of the Health Aspects of Protein Hydrolysates as Food
Ingredients, Supplemental Review and Evaluation-Report 37b-Suppl.,''
(PB80-178643), 1980.
8. FDA opinion letter from Einar T. Wulfsberg, Food and Drug
Officer to Mr. Ratton B. Rogers, the Nestle Co., November 12, 1959.
9. FDA opinion letter from Einar T. Wulfsberg, Food and Drug
Officer to Mr. J. Ter Marsch, August 25, 1961.
10. FDA opinion letter from D. R. Kleber, Jr., Division of
Advisory Opinions Bureau of Enforcement to Yeast Products, Inc.,
January 22, 1962.
11. FDA opinion letter from Virgil O. Wodicka, Director, Bureau
of Foods to Mr. William H. Honstead, The ESU Research Foundation,
Kansas State University, 1972.
12. Advisory Committee on Hypersensitivity to Food
Constituents--Proceedings Ad Hoc, May 8, 1986, pp. 13-28.
13. Reports of the Scientific Committee for Food on a First
Series of Food Additives of Various Technological Functions,
Commission of the European Communities, Reports of the Scientific
Committee for Food, 25th series, 1991.
14. Report of the Council on Scientific Affairs, American
Medical Association, ``Food and Drug Administration Regulations
Regarding the Inclusion of Added L-Glutamic Acid Content on Food
Labels,'' Report: D (A-92), 1992.
15. The Joint Food Agriculture Organization/World Health
Organization Expert Committee on Food Additives, ``L-Glutamic Acid
and its Ammonium, Calcium, Monosodium and Potassium Salts-
Toxicological Evaluation of Certain Food Additives,'' WHO Food
Additive Series, No. 22, pp. 97-161, 1988.
16. Gray, D., FDA memorandum, May 23, 1996.
17. Life Sciences Research Office, Federation of American
Societies for Experimental Biology, ``Analysis of Adverse Reactions
to Monosodium Glutamate (MSG),'' Report, 1995.
18. Allen, D. H., J. Delohery, and G. Baker, ``Monosodium L-
Glutamate-Induced Asthma,'' Journal of Allergy and Clinical
Immunology, vol. 80, pp. 530-537, 1987.
19. FDA memorandum concerning evaluation of the Federation of
American Societies for Experimental Biology (FASEB) (July 1995
Report) from the Director, Division of Health Effects Evaluation to
Lawrence Lin, ``Analysis of Adverse Reactions to Monosodium
Glutamate (MSG),'' August 30, 1996.
20. Levy, A. S., B. M. Derby, Consumer Studies Branch, Center
for Food Safety and Applied Nutrition, FDA, ``The Impact of the NLEA
on Consumers: Recent Findings From FDA's Food Label and Nutrition
Tracking System,'' 1996.
21. Warner, C., and D. Daniels, FDA memorandum, August 14, 1996.
22. United States Department of Agriculture, ``Continuing Survey
of Food Intake by Individuals'' (1989-90, 1990-91, 1991-92),
Nationwide Food Consumption Survey, 1987.
23. Market Research Corporation of America (1992), 5-Year Menu
Census, 1982-87, FDA Contract No. 223-87-2088.
24. DiNovi, M., FDA memorandum, ``Basis for High-Intake
Estimates,'' July 1, 1996.
25. FDA Backgrounder (BG95-16), ``Monosodium Glutamate (MSG),''
August 31, 1995.
26. FDA Warning Letter from Elaine C. Messa, District Director,
Irvine, CA to Patricia Bragg, President, Live Food Products, May 29,
1996.
27. FDA correspondence from John E. Thomas to Sonja L. Valiulis,
October 14, 1992.
28. Hattula, M. T., and H. C. Wallin, ``Enzymatic Determination
of Free Glutamic Acid in Dried Soups and in Minced Sausages: NMKL1
Collaborative Study,'' Journal of the Association of Official
Analytical Chemists, vol. 74, No. 6, pp. 921-925, 1991.
29. Facsimile from H. C. Wallin to C. Warner, May 6, 1996.
30. Daniels, D. H., F. L. Joe, and G. W. Diachenko,
``Determination of Free Glutamic Acid in a Variety of Foods by High-
Performance Liquid Chromatography,'' Food Additives and
Contaminants, vol. 12, No. 1, pp. 21-29, 1995.
31. Yamaguchi, S., and A. Kimizuka, ``Psychometric Studies on
the Taste of Monosodium Glutamate,'' Glutamic Acid: Advances in
Biochemistry and Physiology, Raven Press, New York, pp. 35-54, 1979.
V. Comments
Interested persons may, on or before November 12, 1996, submit to
the Dockets Management Branch (address above) written comments
regarding this ANPRM. Two copies of any comments are to be submitted,
except that individuals may submit one copy. Comments are to be
identified with the docket number found in brackets in the heading of
this document. Received comments may be seen in the Dockets Management
Branch (address above) between 9 a.m. and 4 p.m., Monday through
Friday.
This advance notice of proposed rulemaking is issued under sections
5 and 6 of the Fair Packaging and Labeling Act (15 U.S.C. 1454, 1455),
sections 201, 301, 403, 701 of the Federal Food, Drug, and Cosmetic Act
(21 U.S.C. 321, 331, 343, 371), and under the authority of the
Commissioner of Food and Drugs.
Dated: August 29, 1996.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 96-23159 Filed 9-5-96; 4:43 pm]
BILLING CODE 4160-01-F
