25

GRAS FLAVORING SUBSTANCES 25

By
R .L.2 SMITH,
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COHEN, S. FUKUSHIMA,GOODERHAM,
Table
continuedAverage
Usual Use
Maximum Use N.J.
LevelsS.S.usual
HECHT,MARNETT,
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(ppm)/average
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GRAS flavoring
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as safe (GRAS)
T.B.theADAMS,
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S.V. TAYLOR

Fl avoring Substances 25

The 25th publication by the Expert Panel of the Flavor andExtract Manufacturers Association provides an updateon recent progress in the consideration of flavoring
ingredients generally recognized as safe under the Food
Additives Amendment.

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2

GR AS F L AVORING SUBSTANCES 25

Bloomberg via Getty Images

M

ore than half a century has passed since
the first FEMA Expert Panel began a
program to assess the safety of flavor
ingredients for their intended use in food.
Under the authority provided by the 1958 Food
Additives Amendment to the Food, Drug andCosmetic Act—Public Law No. 85-929, 72 Stat.
1784 (1958), codified at 21 U.S.C. Sec. 348(1988)—the program’s primary objective is toevaluate whether or not substances nominated by
the flavor industry can be considered “generally
recognized as safe” (GRAS) for their intended
use as flavor ingredients. In existence since1960, the FEMA GRAS program has become
the longest-running and most widely recognizedindustry-sponsored GRAS assessment program.
The FEMA GRAS program began with thepassage of the Food Additives Amendment,
which defined a food additive as: “… any
substance … which … may … [become] acomponent or … [affect] the characteristics
of any food … if such substance is not generally recognized, among experts qualified byscientific training and experience to evaluate
its safety, as having been adequately shown
through scientific procedures … to be safe
under the conditions of its intended use.”
This definition removed from consideration
as food additives those substances deemed
GRAS, therefore explicitly excluding them frommandatory premarket approval by the U.S. Foodand Drug Administration (FDA). This allowed
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45 pg

GRAS FLAVORING SUBSTANCES 2525

G R A2ScontinuedF L A V O RAverage
I N G SUsualU B SUseT A Levels/Average
NCES 25
Table
Maximum Use Levels

Average usual use levels (ppm)/average maximum use levels (ppm) for new FEMA GRAS flavoring substanceson which the FEMA Expert Panel based its judgments that the substances are generally recognized as safe (GRAS)

FEMA GRAS Lists

published in Food Technology, in chronological order
Hall, R.L. 1960. Recent progress in theconsideration of flavoring ingredients under
the Food Additives Amendment. Food
Technol. 14: 488-495.
Hall, L. and Oser, B.L. 1961. Recent progressin the consideration of flavoring ingredients
under the Food Additives Amendment. II.
Food Technol. 15(12): 20, 22-26.
Hall, R.L. and Oser, B.L. 1965. Recent progressin the consideration of flavoring ingredients
under the Food Additives Amendment. 3. GRAS
substances. Food Technol. 19(2, Part 2): 151-197.
Hall, R.L. and Oser, B.L. 1970. Recent progressin the consideration of flavoring ingredients
under the Food Additives Amendment. 4. GRAS
substances. Food Technol. 24(5): 25-34.
Oser, B.L. and Hall, R.L. 1972. Recent progressin the consideration of flavoring ingredients
under the Food Additives Amendment. 5. GRAS
substances. Food Technol. 26(5): 35-42.
Oser, B.L. and Ford, R.A. 1973a. Recent progressin the consideration of flavoring ingredients
under the Food Additives Amendment. 6. GRAS
substances. Food Technol. 27(1): 64-67.
Oser, B.L. and Ford, R.A. 1973b. Recent progressin the consideration of flavoring ingredients
under the Food Additives Amendment. 7. GRAS
substances. Food Technol. 27(11): 56-57.
Oser, B.L. and Ford, R.A. 1974. Recent progressin the consideration of flavoring ingredients
under the Food Additives Amendment. 8. GRAS
substances. Food Technol. 28(9): 76-80.
Oser, B.L. and Ford, R.A. 1975. Recent progressin the consideration of flavoring ingredients
under the Food Additives Amendment. 9. GRAS
substances. Food Technol. 29(8): 70-72.
Oser, B.L. and Ford, R.A. 1977. Recent progressin the consideration of flavoring ingredients
under the Food Additives Amendment. 10.
GRAS substances. Food Technol. 31(1): 65-74.
Oser, B.L. and Ford, R.A. 1978. Recent progressin the consideration of flavoring ingredients
under the Food Additives Amendment. 11.
GRAS substances. Food Technol. 32(2): 60-70.
Oser, B.L. and Ford, R.A. 1979. Recent progressin the consideration of flavoring ingredients
under the Food Additives Amendment. 12.
GRAS substances. Food Technol. 33(7): 65-73.
Oser, B.L., Ford, R.A., and Bernard, B.K.
1984. Recent progress in the considerationof flavoring ingredients under the Food
Additives Amendment. 13. GRAS substances. Food Technol. 38(10): 66-89.
Oser, B.L., Weil, C.L., Woods, L.A., andBernard, B.K. 1985. Recent progress in theconsideration of flavoring ingredients under
the Food Additives Amendment. 14. GRAS
substances. Food Technol. 39(11): 108-117.
Burdock, G.A., Wagner, B.M., Smith,R.L., Munro, I.C., and Newberne, P.M.
1990. Recent progress in the consideration
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of flavoring ingredients under the Food
Additives Amendment. 15. GRAS substances.
Food Technol. 44(2): 78, 80, 82, 84, 86.
Smith, R.L. and Ford, R.A. 1993. Recent progressin the consideration of flavoring ingredients under
the Food Additives Amendment. 16. GRAS
substances. Food Technol. 47(6): 104-117.
Smith, R.L., Newberne, P., Adams, T.B., Ford,
R.A., Hallagan, J.B., and the FEMA Expert
Panel. 1996a. GRAS flavoring substances
17. Food Technol. 50(10): 72-78, 80-81.
Smith, R.L., Newberne, P., Adams, T.B., Ford,
R.A., Hallagan, J.B., and the FEMA Expert
Panel. 1996b. Correction to GRAS flavoring
substances 17. Food Technol. 51(2): 32.
Newberne, P., Smith, R.L., Doull, J., Goodman,
J.I., Munro, I.C., Portoghese, P.S., Wagner,
B.M., Weil, C.S., Woods, L.A., Adams, T.B.,
Hallagan, J.B., and Ford, R.A. 1998. GRAS
flavoring substances 18. Food Technol.
52(9): 65-66, 68, 70, 72, 74, 76, 79-92.
Newberne, P., Smith, R.L., Doull, J., Goodman,
J.I., Munro, I.C., Portoghese, P.S., Wagner, B.M.,
Weil, C.S., Woods, L.A., Adams, T.B., Hallagan,
J.B., and Ford, R.A. 1999. Correction to GRAS
flavoring substances 18. Food Technol. 53(3): 104.
Newberne, P., Smith, R.L., Doull, J., Feron,
V.J., Goodman, J.I., Munro, I.C., Portoghese,
P.S., Waddell, W.J., Wagner, B.M., Weil,
C.S., Adams, T.B., and Hallagan, J.B. 2000.
GRAS flavoring substances 19. Food Technol.
54(6): 66, 68-69, 70, 72-74, 76-84.
Smith, R.L., Doull, J., Feron, V.J., Goodman, J.I., Munro, I.C., Newberne, P.M.,
Portoghese, P.S., Waddell, W.J., Wagner,
B.M., Adams, T.B., and McGowen, M.M.
2001. GRAS flavoring substances 20. Food
Technol. 55(12): 34-36, 38, 40, 42, 44-55.
Smith, R.L., Cohen, S.M., Doull, J., Feron,
V.J., Goodman, J.I., Marnett, I.J., Portoghese,
P.S., Waddell, W.J., Wagner, B.M., and Adams,
T.B. 2003. GRAS flavoring substances 21. Food
Technol. 57(5): 46-48, 50, 52-54, 56-59.
Smith, R.L., Cohen, S.M., Doull, J., Feron,
V.J., Goodman, J.I., Marnett, I.J., Portoghese,
P.S., Waddell, W.J., Wagner, B.M., and Adams,
T.B. 2005. GRAS flavoring substances 22. Food
Technol. 59(8): 24-28, 31-32, 34, 36-62.
Waddell, W.J., Cohen, S.M., Feron, V.J.,
Goodman, J.I., Marnett, L.J., Portoghese,
P.S., Rietjens, I.M.C.M., Smith, R.L., Adams,
T.B., Gavin, C. Lucas, McGowen, M.M., andWilliams, M.C. 2007. GRAS flavoring substances
23. Food Technol. 61(8): 22-24, 26-28, 30-49.
Smith, R.L., Waddell, W.J., Cohen, S.M.,
Feron, V.J., Marnett, L.J., Portoghese, P.S.,
Rietjens, I.M.C.M., Adams, T.B., Lucas Gavin,C., McGowen, M.M., Taylor, S.V., and Williams,
M.C. 2009. GRAS flavoring substances 24.
Food Technol. 63(6): 46-48, 51-52, 55-56,
58, 60, 62, 64-66, 68, 70, 72, 74, 76, 78,
80, 82, 84, 86, 88, 90, 92, 94, 96, 98-105.

the FDA to dedicate resources to foodadditive issues of greater safety concern.
The GRAS 25 publication includes theresults of the Expert Panel’s review of 61
new GRAS flavoring substances (Tables
1, 2, and 3). In addition, based on poundage and use level data provided by theInternational Chewing Gum Association(ICGA), the Expert Panel determined that
new use levels for 560 flavoring substancesin the chewing gum category are consistent
with their current GRAS status (Table 4).
In this publication, the Panel also
critically reviews the results of chronic
2-year bioassays performed at the
National Toxicology Program (NTP)
for pyridine (FEMA No. 2966). Also
included are changes in the GRAS statusof two substances recently re-evaluatedby the Expert Panel, an update on the
GRAS status of common salts of GRAS
substances, and an update on thecurrent membership of the Panel.
ICGA Chewing Gum Survey and
FEMA GRAS Re-evaluation

The ICGA (formerly the National Association of Chewing Gum Manufacturers)
conducted surveys of the use of flavoring
ingredients employed in chewing gum in
19721 and again in 1975. These surveys
provided important information on how
flavor ingredients were used in chewing
gum; for instance, between 1972 and1975, 252 additional flavoring substanceswere reported to be used in chewing gum.
Although these surveys were part of an
ongoing ICGA program to periodicallyreview the use of flavors in chewing gum,
this program was superseded by the FDA’s
interest in undertaking a comprehensive
review of the patterns and volumes of use
of food additives and GRAS substancesused in food. The chewing gum surveys
were thus incorporated into regular flavor
poundage surveys performed by the U.S.
flavor industry and sponsored by the FDA
and the National Academy of Sciences.
Although flavor ingredient poundage
used in chewing gum was monitored
approximately every 10 years as part ofthe larger flavor poundage surveys, there
was no ongoing program to monitor thechanges in use levels or the introductionof new flavor ingredients into chewing
gum products during this time. Therefore,

of those 768 flavoring substances are also
FDA-approved food additives or FDA
GRAS substances allowed for use in the
U.S. at levels consistent with good manufacturing practice. In the total number
reported in the ICGA Survey, numerous
flavoring ingredients were determined
to exhibit usual and/or maximum levels
higher than those reported in the earlier
surveys. The Expert Panel had previously
recommended (Smith and Ford, 1993)
that usual and maximum levels that may
potentially result in significantly increased
exposure be re-evaluated; therefore,
ICGA submitted all substances withhigher usual or higher maximum levels
for review to ensure their new uses wereconsistent with current GRAS status.
While not all uses of flavoring
substances in chewing gum were coveredby the ICGA 2000 survey, ICGA estimatedthat more than 95% of the chewing gum
products sold at that time in the UnitedStates were surveyed. The pattern of use of
these substances will obviously vary fromtime to time as the availability and price ofvarious flavoring substances fluctuates or
manufacturers discontinue or modify existing products, or introduce new products.

Photo courtesy of Wild Flavors Inc.

Good Manufacturing Practice for
Chewing Gum Flavoringin 2000, the ICGA decided to perform acomprehensive survey of the addition of flavor ingredients to chewing gum products.
The 2000 ICGA flavor survey2 wasdesigned primarily to determine key
statistics relevant to the total use ofeach flavor ingredient covered by thesurvey in the chewing gum industry
in calendar year 2000, including:1) N umber of manufacturers andnumber of products in which
the substance was used;2) T he average (arithmetic mean)
concentration at which the substancewas used in chewing gum;3) The weighted mean concentration
at which the substance was used;
4) The median concentration atwhich the substance was used;
5) The highest concentration atwhich the substance was used;
6) The total amount of the substance usedin 2000 (calendar year), based on theweighted mean concentration of thesubstance and the volume of chewing
gum disappearing into the marketplace.
The final report covered 768 FEMA
GRAS flavoring substances for which data
related to use in chewing gum were collected for the year 2000. The vast majority

Compared to other food uses, a higher
level of flavoring substance is required in
gum in order to achieve acceptable flavoring properties. Since sufficient flavor must
be available to maintain a palatable taste
for periods of at least 20 minutes, a far
higher concentration of flavoring substanceis used in chewing gum compared to use
in other food products. Chewing also
stimulates an increased flow of saliva,
thus requiring a more concentrated
flavoring to compensate for dilution.
Additionally, a piece of chewing gum
weighs far less than an individual servingof most other food products3. Therefore,a proportionately higher concentrationof flavoring substance must be used toachieve a given quantity of flavoring inchewing gum than in other food products4.
Another key factor that determines
flavor concentration is the retention of flavoring substance within the chewing gum
base. The gum base retains a portion of theflavoring throughout the chewing period. »»07.11 • www.ift.org

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GR AS F L AVORING SUBSTANCES 25

2% menthofuran, the intake of peppermint oil would be 2 mg, and theintake of menthofuran would be 0.04
mg/person or for a 60 kg body weight,
0.0006 mg/kg body weight (0.6 µg/
kg body weight). Although both intakes
are relatively small, intake of menthofuran (0.5 µg/kg body weight) fromchewing a 2 g stick of gum containing
8,000 ppm peppermint oil for 20
minutes is roughly equivalent to theintake of menthofuran from consuming
a 20 g portion of soft candy containing
100 ppm of the same peppermint oil.
FEMA GRAS Re-evaluation

The rate and amount of release of a flavoring agent from a specific gum baseduring chewing, referred to as “chewout,” is also determined in part by the
structure and physicochemical properties of the flavoring substance. Since
saliva is aqueous, the water solubilityof a substance may be related to theamount of chew-out, provided that theflavoring substance does not undergochemical changes that affect theseproperties. ICGA developed a program
to analyze chew-out data for 44
representative flavor ingredients thatare used in chewing gum, and provided
that information to the Panel. The
Panel incorporated these data where
relevant to refine intake estimates
for the applicable flavor ingredientsused in chewing gums that werere-evaluated for FEMA GRAS status.
Determination of Intake of Flavor
Ingredients from Chewing Gum

In order to make meaningfulcomparison of the use and intake offlavoring substances from chewing
gum with the use and intake of thesesubstances in other foods, several
additional factors were considered by
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the Expert Panel. A simple comparisonof the concentrations (in ppm) offlavoring substances in chewing gum
with the concentrations (in ppm)
in other foods is misleading. Morerelevant information is obtained bycomparing the weight of the substanceconsumed on a per serving basis or a
per day basis. For chewing gum, a“serving” is a piece of gum chewed forabout 20 minutes. If the stick is chewed
for a lesser time, it is equivalent topart of a serving because a smaller
portion of the flavoring substance isreleased during a shorter period.
As one example, consider a 2 g(2,000 mg) stick of gum that contains
0.8% (8,000 ppm) peppermint oil,which itself contains 2% menthofuran.
The 2 g stick of gum would contain
16 mg of peppermint oil and 0.32 mgof menthofuran. Upon chewing for
20 minutes, only 10%, or 0.032 mgof the menthofuran, is chewed out. If
the person chewing weighs 60 kg, theintake of menthofuran would be lessthan 0.0005 mg/kg body weight (0.5µg/kg body weight). By comparison, if
a 20 g portion of soft candy contained
100 ppm peppermint oil that contained

The Panel re-evaluated all relevant
metabolic and toxicity data for theseflavor ingredients within the context
of their increased use levels in chewing
gum. The intake of flavoring substancefrom chewing gum—given its lightweight per serving, flavor retention
rates, but seemingly high added concentrations—may be roughly equivalent
to the intake of these same substances
at lower concentration in foods that are
consumed over a shorter time period
and have a much greater portion size.
Therefore, in cases where the relevant
data were available, the intake related
to use of these flavor ingredients inchewing gum was evaluated in thecontext of the effects of portion size,
level of chew-out, and other factors
affecting the intake of the flavor
ingredient. Based on their review of theintake data, and the relevant metabolicand toxicity data for these substances,
the FEMA Expert Panel determinedthat the new or higher use levels inchewing gum for the 560 flavoring
ingredients listed in Table 4 are consistent with their current GRAS status.
Safety Assessment of
Pyridine (FEMA No. 2966)

At ppm levels, the aroma of pyridine
is described as warm, burnt, andsmoky (Arctander, 1969). Based upona reported annual volume of pyridineof 54 kg in the United States (Gavin etal., 2008), the daily per capita intake(“eaters only”)5 of pyridine from use
as a flavor ingredient is calculated tobe 7 µg/person/day. Pyridine has been

Photo courtesy of Bell Flavors & Fragrances Inc.

2
isolated in the volatile components
from cooked beef (sukiyaki) in
Japan (Shibamoto et al., 1981);
fried chicken in the U.S. (Tang etal., 1983); fried bacon (Ho et al.,1983); Beaufort cheese (Dumontand Adda, 1978); black tea aroma(Vitzthum et al., 1975); and coffee
aroma (Aeschbacher et al., 1989).
An 8 oz cup of fresh brewed coffee
may contain up to 5 µg of pyridine.
Concentrations in cocoa (0.5 ppm),
coffee (37–49 ppm), and shrimp(4.1–9.9 ppm) represent principal
food sources of pyridine (Nijssen
et al., 2010). Based on quantitative
natural occurrence data, the intakeof pyridine from consumption of
all traditional foods exceeds its
intake as an added flavor ingredientby a factor of at least 100 (Stofberg
and Kirschman, 1985; Stofberg
and Grundschober, 1987).
In animals, pyridine ismetabolized primarily by twobiotransformation routes: oxidation at the nitrogen atom to givepyridine N-oxide and methylationof the nitrogen atom to yieldthe quaternary ammonium ion,
N-methylpyridinium. Both polar
metabolites are excreted in theurine (D’Souza et al., 1980;
Damani et al., 1982). To a lesser
extent, ring oxidation may occur
to give 2- and 4-pyridone and3-hydroxypyridine. In vitro
experiments with human and rat
microsomal and cytosolic liver fractions, and human microsomal andcytosolic kidney and lung fractions,show the formation of these threering-oxidized metabolites (Wilke
et al., 1989). In vivo studies inrats demonstrate that CYP2E1 is
induced by pyridine and is responsible for formation of pyridine
N-oxide (Kim et al., 1988; Kaul
and Novak, 1987). Other pyridineinduced isoforms include rat renal
CYP1A1 and CYP1A2 (Kim et al.,1995), rat hepatic CYP2B1/2B2(Kim et al., 1993), and rabbit liver
CYP2B1/2B2 (Kim et al., 1991).

In two separate 90-day studies,groups of 10 male and 10 female
F344/N or 10 male Wistar rats
were provided drinking watercontaining pyridine at concentrations of 0, 50, 100, 250, 500, or
1,000 ppm (equivalent to average
daily doses of 5, 10, 25, 55, or
90 mg pyridine/kg body weight)(NTP, 2000). For the F344/N rats,
in addition to increased mortality(2 females at 1,000 ppm), dehydration and decreased body weights
were reported at the two highest
concentrations. On day 5, erythrocytosis was reported in males
at concentrations of 100 ppm andgreater. This observation is consistent with dehydration, which cancause relative erythrocytosis due todecreased blood volume and hemoconcentration (Jain, 1986). On day
20, the erythrocytosis was replaced
by a developing normocytic,
normochromic, non-responsive
anemia, demonstrated by decreased
hematocrit values, hemoglobin
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Photo courtesy of Bell Flavors & Fragrances Inc.

GR AS F L AVORING SUBSTANCES 25

concentrations, and erythrocyte counts relative
to controls in males and females exposed toconcentrations of 250 ppm or greater. At study
termination, evidence of anemia persisted in the
500 and 1,000 ppm males and all exposed groupsof females. At the two highest concentrations,
there was evidence of hepatocellular injury and/or altered hepatic function (increased serum alanine aminotransferase and sorbitol dehydrogenase
activities and bile acid concentrations). Liverweights of males and females exposed to 250
ppm or greater were significantly greater thancontrols. The incidences of hepatic centrilobular
degeneration, hypertrophy, chronic inflammation, and pigmentation were generally increased
in 500 and 1,000 ppm males and females relative
to controls. In the kidney, the incidences of
granular casts and hyaline degeneration (hyaline
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droplets) were significantly
increased in 1,000 ppm males
and slightly increased in 500
ppm males; these lesions suggested alpha-2u-globulin-type
nephropathy. Additionally, there
were increased incidences and/or
severities of protein casts, chronic
inflammation, mineralization,and regeneration primarily in 500
and 1,000 ppm males. Based on
the appearance of erythrocytosis
in males at 100 ppm, the NOAEL(no observed adverse effectlevel) was concluded to be 50
ppm or approximately 5 mg/
kg body weight per day.
Responses (lower mean bodyweights, dehydration, and hepatic
injury) in male Wistar rats
provided pyridine in drinking
water were similar to those in
F344/N rats and occurred ina similar concentration range,
and the NOAEL in Wistar rats
was at a concentration of 100
ppm, or approximately 10 mg/
kg body weight per day. Groupsof 10 male and 10 female B6C3F1
mice were exposed to the same
concentrations of pyridine as
used in the 90-day rat study.
Based on increased liver weights
relative to controls in males
exposed to 100 ppm or greater,
the NOAEL was concluded to
be 50 ppm or approximately 5
mg/kg body weight per day.
In a 2-year bioassay performed by the National
Toxicology Program (NTP, 2000), groups of
50 B6C3F1 mice of both sexes were exposed
to pyridine in drinking water at concentrations
calculated to provide an average daily intake of0, 35, 65, or 110 mg/kg body weight for males
and 15, 25, or 70 mg/kg body weight for females.
Based on the results of the 2-year drinking water
study in B6C3F1 mice, the NTP reached thefollowing conclusion: “There was clear evidence of
carcinogenic activity of pyridine in male and female
B6C3F1 mice based on increased incidencesof malignant hepatocellular neoplasms.”
Hepatocellular adenomas occurred at anincreased incidence in males (29/50 in controls,
40/50 (p = 0.003), 34/49, and 39/50 (p = 0.011)
in low-, mid-, and high-dose groups, respectively.
The incidence of hepatocellular carcinomas inmales was 15/50 in controls, 35/50 in
the low-, 41/49 in the mid-, and 40/50
in the high-dose group, respectively(p < 0.001, pairwise comparisons for
all treated groups). The incidence ofhepatoblastomas in males was 2/50,
18/50, 22/49, and 15/50 (p < 0.001,
pairwise comparisons for all treatedgroups) in control, low-, mid-, andhigh-dose groups, respectively. In
female mice, the incidence of hepatocellular carcinomas was increased
in a dose-related manner: 13/49 incontrols, 23/50, 33/50 (p = 0.014),
and 41/50 (p < 0.001) in the low- mid-,and high-dose groups, respectively.
The incidence of hepatoblastomas was
also dose-dependent and significantly
increased: 1/49 in controls, 2/50,
9/50 (p = 0.007), and 16/50 (p <0.001) in the low-, mid-, and high-dosegroups, respectively (NTP, 2000).
The statistical evidence of increased
incidence of liver neoplasms must be
evaluated in the context of strain andspecies-specific effects recently elucidated in the B6C3F1 mouse (Turosov,2002). Shortly after publication of the
2-year bioassay with pyridine, the NTP
reported an unexpected 5-fold increasein the incidence of spontaneous hepatoblastomas in control B6C3F1 mice
during the period 1994–2002. This
was accompanied by an increase in theincidence of chemically induced hepatoblastomas in B6C3F1 mice in 2-year
NTP studies compared to the previous
7 years. There was a positive association
between an increased incidence of micewith hepatoblastoma and an increased
incidence of mice with hepatocellulartumors. Although a variety of chemicals
caused an increased incidence ofmice with hepatoblastoma, there was
no apparent association between a
specific chemical structure and theircapacity to induce hepatoblastomas.
Hepatoblastoma is a component of thespectrum of hepatocellular tumors thatare identified separately in addition to
hepatocellular adenoma and carcinoma
in a study. Chemicals that induce
hepatoblastomas and hepatocellular
carcinomas are not necessarily morepotent than chemicals that induce
hepatocellular carcinomas alone.
Because hepatoblastomas frequently
arise within hepatocellular adenomas
and hepatocellular carcinomas, thestudy authors (Turosov et al., 2002)concluded that it is reasonable tocombine the incidence of mice with
hepatoblastomas with the incidence ofmice with hepatocellular adenomas andhepatocellular carcinomas in the overall
evaluation for hazard classification.
The overall rates of tumor incidence
for combined hepatocellular adenomas,
carcinomas, and blastomas for male
B6C3F1 mice exposed to pyridine was
38/50 (76%) in controls, 47/50 (94%)
in the low-, 46/49 (94%) in the mid-,and 47/50 (94%) in the high-dosegroups. The combined tumor incidence
for female B6C3F1 mice was 41/49(84%) in controls, 42/50 (84%) in thelow-, 45/50 (90%) in the mid-, and44/50 (88%) in the high-dose groups.
Therefore, there are no statisticallysignificant differences in tumor incidence between test and control groupsof either sex of mice. The increase inspontaneous background incidence ofliver neoplasms in male B6C3F1 micein the 2-year NTP bioassay is now
well recognized. This phenomenon
has been reported in 2-year studies
for other flavor ingredients (Smithet al., 2009; Adams et al., 2005). It
is also generally well accepted thatmale and female B6C3F1 mouse liver
tumors that arise in 2-year bioassays
with various agents (e.g., chloroform;
see Meek et al., 2003) can be theresult of dose-related chronic toxicity
and resulting regenerative cellular
proliferation. In the absence of thischronic toxicity at exposure levels
in humans, the occurrence of thesetumors does not provide evidence thatpyridine represents a significant riskfor humans (Cohen et al., 2004).
There is substantial evidence thatthe appearance of male B6C3F1 mouse
liver tumors is not relevant to a humanrisk assessment. First, there was no
statistical evidence of an increased incidence of total hepatic tumors in maleor female rats related to administrationof pyridine. Second, all dose groups
of male and female B6C3F1 mice
suffered chronic hepatic toxicity prior
to the development of liver adenomas,
carcinomas, or blastomas, as evidenced
by the results of the 90-day and2-year studies. Hepatocellular tumors
also occurred late in the life span ofboth male and female mice. From abiological perspective, the increase in
the incidence of tumors in B6C3F1
mice reflects the impact of high-doseliver damage to an organ already prone
to spontaneous development of liver

Expert Panel Member Changes
In May 2010, Phillip Portoghese of the University of Minnesota retired
from the Panel. Portoghese spent more than a quarter-century inservice to the Expert Panel and the flavor industry. His experience inbiochemistry, medicinal chemistry, and metabolism provided the Panelwith expertise that contributed significantly to the long-standing
success of the Panel.
In October 2010, William Waddell of the University of Louisvilleretired from the Panel after more than a decade of service. Withextensive experience in pharmacology, toxicology, medicine, andmechanisms of carcinogenicity, Waddell made numerous key
contributions to the work of the Panel. Portoghese and Waddell are now
recognized as Emeritus Members of the Panel.
In September 2010, Stephen Hecht, Professor of Cancer Prevention at the
University of Minnesota, joined the Panel. His work focuses on the role ofcarcinogen metabolism and DNA binding in mechanisms of carcinogenesis.
In September 2010, Shoji Fukushima, Director at the Japan Bioassay
Research Center, joined the Panel. Fukushima has published numerous
articles with a research focus on the mechanisms of carcinogenesis.
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Photo courtesy of Virginia Dare

Photo courtesy of Wild Flavors Inc.

Photo copyright©iStockphoto.com/Elemental Imaging

GR AS F L AVORING SUBSTANCES 25

neoplasms (Smith et al., 2009; Haseman et al., 1986; Haseman, 1990).
Therefore, it can be concluded thatthe carcinogenic potential in this sensitive strain and sex of laboratory mouseis a secondary biological response to
dose-dependent hepatotoxicity, and is
not relevant to humans who consume
pyridine at low nontoxic levels(<0.0005 mg/kg body weight perday) from intended use as a flavoring
ingredient or as a constituent of food.
The 90-day NOAEL of either 5 or 10
mg/kg body weight per day in Fisher
F344/N or male Wistar rats, respectively, (NTP, 2000) is approximately
1,000 times the daily per capita intake(“eaters only”) intake of 0.007 mg/
kg body weight per day from use ofpyridine as a flavor ingredient. Also,these levels of intake are at least fourorders of magnitude lower than thoseused in the NTP bioassay that resulted
in hepatic toxicity and neoplasms.
In the rat 2-year bioassay, groupsof 50 F344/N rats of both sexes were
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exposed to pyridine in the drinking
water at concentrations calculated toprovide an average daily intake of 0, 7,
14, or 33 mg/kg body weight per day.
In a second strain of rats, groups ofmale Wistar rats were maintained on
drinking water containing pyridine atconcentrations calculated to provide
an average daily intake of 0, 8, 17,
or 36 mg/kg body weight per day.
Consistent with the 13-weekstudies, the target organs included
the liver and kidney in male F344/N
rats, the liver and testes in Wistar
rats, and the liver in female F344/N
rats. Although, in general, these liverlesions were more severe in Wistar
rats than in F344/N rats, there was
no evidence of an increase in theincidence of hepatocellular neoplasmsin either sex or strain of treatedrats compared to controls. The only
evidence of neoplasms occurred in thekidney where there was an increased
incidence of renal tubule adenomas inmale F344/N rats [2/50 (4%) in thecontrols, 3/48 (4%) in the low-, 6/50
(12%) in the mid-, and 10/50 (20%)
in the high-dose groups] in the 2-yearbioassay based on evaluation of single
and multiple sections combined. Basedon these results, the NTP concluded:“Under the conditions of these 2-year
drinking water studies, there was someevidence of carcinogenic activity of pyridine
in male F344/N rats based on increased
incidences of renal tubule neoplasms.”
Although the NTP noted the presence of hyaline droplets, granular casts,
and immunohistochemical evidenceof alpha 2u-globulin nephropathy, thedroplets and casts were clearly lesssevere than for other alpha 2u-globulin
nephropathy inducers and there wereno linear foci of mineralization within
the renal medulla in this study, achange normally characteristic of alpha2u-globulin-associated nephropathy.
Based primarily on these observations, the NTP suggested that therenal neoplastic response in the male
F344/N rat kidney was not attributable
to alpha 2u-globulin nephropathy.
Although the incidence and severityof renal tubular neoplasms associatedwith the formation of hyaline dropletsis evident in treated males, the lack ofany evidence of renal tubular adenomas
and carcinomas in female F344 rats
and male Wistar rats and the lack ofrenal changes in mice clearly establishes
that the carcinogenic response is sex-,
strain-, and species-specific. One carcinoma was recorded in male F344/N
rats, and that result is not considered
to be treatment related in that it
occurred only in the low-dose group.
Renal tubule hyperplasia was slightly
increased in male F344/N rats [9/50(18%) in the controls, 7/48 (15%) in
the low-, 11/50 (22%) in the mid-, and15/50 (30%) in the high-dose groups].
The hyperplastic and the benign tumorigenic response (adenomas only) in male
F344/N rats are weak compared to thatfor other alpha 2u-globulin inducers.
Although the proliferative responsein the male F344/N rats is slight andthere is a lack of known mineralization
characteristic of alpha 2u-globulin
nephropathy, the immunohistochemical evidence from the 13-week study

at higher concentrations cannot
be dismissed. Pyridine is nongenotoxic based on mainly negative
results in both in vitro and in vivo
assays (Pai et al., 1978; NTP, 2000;
MacGregor et al., 2000; Harper
et al., 1984; Kawachi et al., 1980;
Warren et al., 1981; Riebe et al.,
1982; Florin et al., 1980; Haworth
et al., 1983; Abe and Sasaki, 1977;
Ishidate and Odashima, 1977), so
the mode of action for induction of
the renal tumors is non-genotoxic
and dependent on dose-related
increase in proliferation. The
specific mode of action for thesepyridine-induced renal tumors
remains to be established.
The other carcinogenic
effect reported by NTP was anincreased incidence of mononuclear
cell-leukemia in female F344/N
rats. They noted that incidencesof mononuclear cell leukemia
in female rats were slightly but
significantly increased in the 200
and 400 ppm groups compared tocontrols [12/50 (24%) in controls,
16/50 (32%) in the low-, 22/50(44%) in the mid-, and 23/50(46%) in the high-dose groups],
and that the incidence in the 400
ppm group exceeded the historicalcontrol range. The mean historicalincidence in 2-year drinking waterstudies with untreated control
groups is 30.9% (± 10.0%) with arange of 16–44%. In males, there
was no statistically significant
difference in the incidence ofmononuclear cell leukemia, but
the rates were all higher than infemales (0 ppm, 29/50; 100 ppm,
32/50; 200 ppm, 26/50; 400 ppm,
27/50). There was no increased
incidence of leukemia in male
Wistar rats: this strain exhibits alow spontaneous incidence of thistype of tumor. In all animals withthis neoplasm, neoplastic cells were
found in the spleen and usuallyalso in the liver. Infiltrations in
the lung, bone marrow, lymph
nodes, adrenal gland, and kidney
were also common. Incidencesof mononuclear cell leukemia inmale rats were similar to thosein controls and in the same range
as for females at the two higher
dose levels (0 ppm, 29/50; 100ppm, 32/50; 200 ppm, 26/50;
400 ppm, 27/50). Based on themarginal increase in leukemia infemales at 200 and 400 ppm, theNTP concluded that: “There was
equivocal evidence of carcinogenic activity of pyridine in female F344/N
rats based on increased incidencesof mononuclear cell leukemia.”More than 20 years ago,
members of NTP reported (Raoet al., 1990) that the incidenceof mononuclear cell leukemia infemale F344/N rats in drinking
water studies had been steadily
increasing. From a low of 2.1% in
1971, control rates had increased
to over 30% in females. The trend
is more pronounced in males,
where rates had climbed from
7.9% to as high as 52% (Haseman
and Rao, 1992). More recently,
as a result of a workshop that
focused on whether the choice ofanimal models used by the NTP
should be changed (King-Herbert
and Thayer, 2006), the NTP has
now concluded that the Harlan
Sprague-Dawley rat will replace theF344/N strain as the animal modelin future bioassays (King-Herbert
et al., 2010). In the NTP study on
pyridine using F344/N rats, while
statistically significant increases
in the incidence of mononuclear
cell neoplasms in female rats werereported, the biological significanceof these tumors and their relevanceto humans remains uncertain.
Pyridine was reaffirmed as
GRAS (GRASr) in 2010 based
upon its efficient detoxificationin humans; its low level of flavor
use; the lack of genotoxic andmutagenic potential; the safety
factor calculated from results ofsubchronic studies (NTP, 2000)
indicating a margin of safety of atleast 1,000; the conclusion thatthe statistically significant findingsin the NTP mouse bioassay, of anincreased incidence of hepatocel-lular neoplasms in male and female
B6C3F1 mice were secondary
to pronounced hepatotoxicity athigh dose levels; the conclusionthat the increased incidence ofrenal neoplasms in male F344/N
rats occurs via a dose-dependent
non-genotoxic mode of action; andthe conclusion that the increased
incidence of mononuclear cellleukemia in female F344/N rats
is likely species- and sex-specific,
the biological significance of
which remains uncertain. Basedon these conclusions, the use ofpyridine as a flavor ingredient is
not considered to produce any
significant risk to human health.
This evaluation is supported by theoccurrence of pyridine as a naturalcomponent of traditional foods
resulting in concentrations in thediet producing a “natural intake”
that is at least 100 times higher thanthat which occurs when pyridine
is employed as a flavor ingredient.

2

ReGRAS of 2-Methyl-5-vinylpyrazine
and 2-Hexyl-4-acetoxytetrahydrofuran

The substance 2-methyl-5-vinylpyrazine (formerly FEMA No.
3211) was removed from the GRAS
list in 1984 (Oser et al., 1984).
At that time, the substance wasreevaluated by the panel and found
to require additional data including
toxicological testing for continuation of GRAS status. Additional
metabolism data supporting side
chain oxidation of the substanceand toxicity data from a 90-day
study on the structurally related
substance 2-vinylpyridine were
presented to the Panel in October
2009. Based upon an evaluationof these data, the Panel concluded
that 2-methyl-5-vinylpyrazine is
GRAS under conditions of intended
use as a flavor ingredient. The
Panel restored the GRAS status of
2-methyl-5-vinylpyrazine with its
original FEMA GRAS number.
The substance 2-hexyl4-acetoxytetrahydrofuran(formerly FEMA No. 2566) wasremoved from the GRAS list
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53 pg

25
Photo courtesy of Virginia DareGR AS F L AVORING SUBSTANCES 25

in 1970 due to questions concerning certain
isomeric components. In May 2010, clarificationof chemical identity and purity was submitted
to the Panel together with data supporting thehydrolysis of the ester. The Panel concluded
that its FEMA GRAS status should be restoredwith its original FEMA GRAS number.
Panel Statement on Salt Forms of FEMA GRAS Substances

The FEMA Expert Panel concludes that theneutral, hydrated, and salt forms of GRAS
substances that are physiologically equivalent
are assigned the same GRAS number. Suchsalt forms include the chlorides, sulfates,
carbonates, bicarbonates, and phosphatesof quaternary ammonium and sulfonium
salts. The same GRAS number would also be
applied to the sodium, potassium, calcium,
ferrous, ferric, ammonium, and quaternaryammonium salts derived from FEMA GRAS
amines, carboxylates, sulfonates, sulfamates,or sulfates, provided the level of intake of therespective mineral in the salt is sufficiently low
compared to dietary intake of these minerals. FT
Robert L. Smith, Chairman of the FEMA Expert Panel, is Professor,
Emeritus, and Senior Research Fellow in Molecular Toxicology,
Imperial College London. William J. Waddell, Past Chairman of the
FEMA Expert Panel, is Professor and Chair, Emeritus, Dept. of
Pharmacology and Toxicology, University of Louisville Schoolof Medicine, Louisville, Ky. Other members of the FEMA Expert
Panel are Samuel M. Cohen, Havlik-Wall Professor, Dept. of
Pathology and Microbiology, University of Nebraska Medical
Center, Omaha, Neb.; Shoji Fukushima, Japan Bioassay ResearchCenter, Kanagawa, Japan; Nigel J. Gooderham, Professor in
Molecular Toxicology, Dept. of Surgery and Cancer, Imperial
College London; Stephen S. Hecht, Professor and Wallin Chair inCancer Prevention, Dept. of Laboratory Medicine and Pathology,
University of Minnesota, Minneapolis, Minn.; Lawrence J. Marnett,
Dept. of Biochemistry, Vanderbilt School of Medicine, Vanderbilt
University, Nashville, Tenn.; Philip S. Portoghese, Professor, Collegeof Pharmacy, University of Minnesota, Minneapolis, Minn.; andIvonne M.C.M. Rietjens, Professor and Chair, Dept. of Toxicology,
Wageningen University, Wageningen, The Netherlands.
Timothy B. Adams is the Scientific Secretary for the FEMA Expert
Panel and Scientific Director of FEMA. Christie Lucas Gavin,
Margaret McGowen, and Sean Taylor, Assistant Scientific Directorof FEMA, are associated with the Flavor and Extract Manufacturers
Association, 1620 I Street, NW, Suite 925, Washington, DC 20006.
Send reprint requests to author Adams (tadams@vertosolutions.net).

NOTES
For a description of previous surveys conducted by the NACGM, see “Introduction to NACGM Flavor Survey Final Compilationof Data,” Aug. 1, 1972, Exhibit 20 to “A Comprehensive Survey of Industry on the Use of Food Chemicals Generally Recognized
as Safe (GRAS),” Subcommittee on Review of the GRAS list—Phase II, Committee on Food Protection, Food and Nutrition
Board, Division of Biology and Agriculture, National Research Council (National Academy of Sciences, September, 1972).
2
Full details related to the methodology and results of the survey, as well as data related to retention/release of flavor ingredientsfrom chewing gum matrices, are expected to be reported elsewhere.
3
A stick of ordinary slab chewing gum weighs about 2 g, and a piece of bubblegum weighs about 5 g. The flavor ordinarily
represents 0.5%–1.5% of the product, but in some instances ranges up to 3.0% or even higher.
4
It should be noted in passing that the very same factors which require a much higher concentration of flavoring in chewing gum
than in other foods also substantially reduce the potential toxicity of the use of these higher levels.
5
Intake (µg/person/day) calculated as follows: (((annual volume, kg) x (1 x 109 µg/kg))/(population x survey correction factor x 365days)), where population (10%, “eaters only”) = 28 x 10 6 for the U.S.; where correction factor = 0.8 represents the assumptionthat only 80% of the flavor volume was reported in the 2005 survey (Gavin et al., 2008). Intake (µg/kg body weight per day)calculated as follows: [(µg/person/day)/body weight], where body weight = 60 kg. Slight variations may occur from rounding off.
1

pg 54

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GRAS FLAVORING SUBSTANCES 25

Table 1. Primary Names & Synonyms

Primary names (in boldface) & Synonyms (in lightface)

FEMA NO.

FEMA NO.

Substance primary names and synonyms

4682

OCTAHYDRO-4,8A-DIMETHYL-4A(2H)-NAPHTHOL
Geosmin
Octahydro-4,8a-dimethyl-4a(2H)-naphthol
4,8a-Dimethyloctahydronaphthalen-4a(2H)-ol
4a(2H)-Naphthalenol, octahydro-4,8a-dimethyl1,10-Dimethyl-9-decalol

4683(2E,6E/Z,8E)-N-(2-METHYLPROPYL)-2,6,8-DECATRIENAMIDE
Spilanthol
N-Isobutyl-2E-decenamide
Affinin

2-METHYL-4,5-DIHYDROFURAN-3-THIOL
3-Furanthiol, 4,5-dihydro-2-methyl2-Methyl-4,5-dihydrofuran-3-thiol
3-Mercapto-2-methyl-4,5-dihydrofuran
4,5-Dihydro-2-methyl-3-mercaptofuran

4684

4-AMINO-5,6-DIMETHYLTHIENO[2,3-D]PYRIMIDIN-2(1H)-ONE
4-Amino-5,6-dimethylthieno[2,3-d]pyrimidin-2(1H)-one hydrochloride(2S,5R)-N-[4-(2-AMINO-2-OXOETHYL)PHENYL]-5METHYL-2-(PROPAN-2-YL)CYCLOHEXANECARBOXAMIDE
Benzeneacetamide, 4-[[[(2S,5R)-5-methyl-2-(1methylethyl)cyclohexyl]carbonyl]amino]-4685(±)-6-OCTYLTETRAHYDRO-2H-PYRAN-2-ONE
5-Tridecanolide
6-Octyltetrahydro-2H-pyran-2-one
Tetrahydro-6-octyl-2H-pyran-2-one
delta-Tridecalactone
5-Hydroxytridecanoic acid delta lactonedelta-Octylvalerolactone
Trideca-1,5-lactone

4686(±)-2-METHYLTETRAHYDROFURAN-3-THIOL ACETATE
2-Methyltetrahydrofuran thioacetate
2-Methyl-3-thioacetoxytetrahydrofuran
Ethanethioic acid, S-(tetrahydro-2-methyl-3-furanyl)ester
2-Methyltetrahydrofuran-3-thiol acetate4687(±)-3-HYDROXY-3-METHYL-2,4-NONANEDIONE
Lactadione

4688

1,1-DIPROPOXYETHANE
Acetaldehyde, dipropyl acetal

4689

CHRYSANTHEMUM EXTRACT
Chrysanthemum morifolium, ext.

4690

HONEYSUCKLE EXTRACT
Honeysuckle, Lonicera japonica, ext.

4691

YUZUNONE
6,8E,10-Undecatrien-3-one

4692

L-METHIONYLGLYCINE

4693

1-(2-FURFURYLTHIO)PROPANONE
1-(Furan-2-ylmethylsulfanyl)propan-2-one
2-Propanone, 1-[(2-furanylmethyl)thio](Furfurylthio)acetone
1-[(2-Furylmethyl)sulfanyl]acetone

N-CYCLOPROPYL-5-METHYL-2ISOPROPYLCYCLOHEXANECARBOXAMIDE
Cyclohexanecarboxamide, N-cyclopropyl5-methyl-2-(1-methylethyl)-4694

3-PENTANETHIOL
Pentane-3-thiol
3-Pentyl mercaptan

4677(±)-4-METHYL-2-PROPYL-1,3-OXATHIANE
1,3-Oxathiane, 4-methyl-2-propyl-

4695

2-ETHYL-2,5-DIHYDRO-4-METHYLTHIAZOLE
2-Ethyl-4-methyl-3-thiazoline

4678

N-(2-METHYLCYCLOHEXYL)-2,3,4,5,6-PENTAFLUOROBENZAMIDEPFMC Benzamide

4696

4679

ARACHIDONIC ACID ENRICHED OIL
AREOArasco1-(METHYLDITHIO)-2-PROPANONE
Methyl 2-oxopropyl disulfide
1-(Methyldisulfanyl)acetone
1-Methyldisulfanylpropan-2-one

4697

4680

5-ISOPROPYL-2,6-DIETHYL-2-METHYLTETRAHYDRO-2H-PYRAN
2,6-Diethyl-2-methyl-5-(propan-2-yl)tetrahydro-2H-pyran
2H-Pyran, 2,6-diethyltetrahydro-2-methyl-5-(1-methylethyl)-

5-METHYLFURFURYLMERCAPTAN(5-Methylfurfuryl)mercaptan
5-Methyl-2-furanmethanethiol(5-Methylfuran-2-yl)methanethiol

4681(1R,2S,5R)-N-(4-METHOXYPHENYL)-5-METHYL-2(1-METHYLETHYL)CYCLOHEXANECARBOXAMIDE
N-(4-Methoxyphenyl)-p-menthanecarboxamide(1R,2S,5R)-N-(4-Methoxyphenyl)-5-methyl-2(1-methylethyl)cyclohexanecarboxamide

4698

4-MERCAPTO-3-METHYL-2-BUTANOL
4-Mercapto-3-methylbutan-2-ol
3-Methyl-4-sulfanyl-2-butanol
4-Thio-3-methyl-2-butanol

4699

FERROUS L-LACTATE
L-2-Hydroxy-propanoic acid, iron (2+) salt dihydrate

2566

2-HEXYL-4-ACETOXYTETRAHYDROFURAN (RE-GRAS)
3-Furanol, 5-hexyltetrahydroacetate

3211

2-METHYL-5-VINYLPYRAZINE (RE-GRAS)
Pyrazine, 2-ethenyl-5-methyl-4667

2(4)-ETHYL-4(2),6-DIMETHYLDIHYDRO-1,3,5DITHIAZINE (MIXTURE OF ISOMERS)
2(4)-Ethyl-4(2),6-dimethyldihydro-1,3,5-dithiazinane
Ethyl thialdine

4668

4669

4670

1,1-PROPANEDITHIOL
1,1-Dimercaptopropane

4671

Z-5-OCTENYL ACETATE
cis-5-Octenyl acetate(5Z)-Octen-1-ol acetate4672(E)-4-UNDECENAL
trans-Undec-4-enal
4E-Undecenal

4673

DELTA-HEXADECALACTONE
Tetrahydro-6-undecyl-2H-pyran-2-one
6-Undecyltetrahydropyran-2-one
delta-Hexadecanolidedelta-Palmitolactone
5-Hexadecanolide
5-Hydroxyhexadecanoic acid delta lactone
6-Undecyltetrahydro-2H-pyran-2-one

4674

4675

4676

pg 56

Substance Primary Name and Synonyms

TRILOBATIN
Prunin dihydrochalcone
Phloretin 4’-glucoside
1-Propanone, 1-[4-(beta-D-glucopyranosyloxy)2,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)L-ISOLEUCINE(S)-Isoleucine(2S,3S)-2-Amino-3-methylpentanoic acid
[S-(R*,R*)]-2-Amino-3-methylpentanoic acid07.11 • www.ift.org

FEMA NO.

Substance Primary Name and Synonyms

FEMA NO.

Substance primary names and synonyms

4700

O-TRANS-COUMARIC ACID
2-Propenoic acid, 3-(2-hydroxyphenyl)-, (E)Cinnamic acid, o-hydroxy-, (E)(E)-2-Hydroxycinnamic acid

4714

ETHYL 2-MERCAPTO-2-METHYLPROPIONATE
Ethyl 2-methyl-2-sulfanylpropanoate
Ethyl 2-mercapto-2-methylpropanoate
Propanoic acid, 2-mercapto-2-methyl-, ethyl ester4701

3-[(4-AMINO-2,2-DIOXIDO-1H-2,1,3-BENZOTHIADIAZIN5-YL)OXY]-2,2-DIMETHYL-N-PROPYLPROPANAMIDE
3-(4-Amino-1H-benzo[c][1,2,6]thiadiazin-5-yloxy2,2-dimethyl-N-propylpropanamide-2,2-dioxide
3-(1H-Benzo[c][1,2,6]thiadiazin-4-amine-2,2-dioxide)5-yloxy-2,2-dimethyl-N-propylpropanamide4715

2-(3,4-DIHYDROXYPHENYL)-5,7-DIHYDROXY-4-CHROMANON
4H-1-Benzopyran-4-one, 2-(3,4-dihydroxyphenyl)2,3-dihydro-5,7-dihydroxy(±)-Eriodictyol(±)-3’,4’,5,7-Tetrahydroxyflavanone

4702

2(3),5-DIMETHYL-6,7-DIHYDRO-5H-CYCLOPENTAPYRAZINE

4716

4703

CINNAMYL BENZOATE
3-Phenyl-2-propenyl benzoate

N-[N-[3-(3-HYDROXY-4-METHOXYPHENYL)PROPYL]-L-ALPHAASPARTYL]-L-PHENYLALANINE 1-METHYLESTER, MONOHYDRATE
Advantame

4717

4704

BETA-NAPHTHYL METHYL ETHER
2-Methoxynaphthalene
2-Naphthol methyl ether
2-Naphthyl methyl ether

SWEET BLACKBERRY LEAVES EXTRACT
Chinese Blackberry Extract
Rubus suavissimus S. Lee, ext.
Rubus chingii Hu, ext.
Rubus palmatus Thunb., ext.

4705

ROSEMARY OLEORESIN
Rosemarinus officinalis oleoresin

4718

4706

9-DECEN-2-ONE
Dec-9-en-2-one
Methyl oct-7-enyl ketone

2-[2-(P-MENTHYLOXY)ETHOXY]ETHANOL
2-[(2-p-Menthoxy)ethoxy]ethanol
2-[2-(2-Isopropyl-5-methyl-cyclohexyloxy)ethoxy]-ethanol
2-[2-(p-Menthan-3-yloxy)ethoxy]ethanol

4719

SUCCINIC ACID
Butanedioic acid
1,2-Ethanedicarboxylic acid4707

1-(METHYLTHIO)-3-OCTANONE
1-Methylsulfanyloctan-3-one

4720

4708

3’,7-DIHYDROXY-4’-METHOXYFLAVAN(±)-3’,7-Dihydroxy-4’-methoxyflavan
3,4-Dihydro-2-(3-hydroxy-4-methoxyphenyl)2H-1-benzopyran-7-ol

REBAUDIOSIDE C
Dulcoside B

4721

1-(2-HYDROXYPHENYL)-3-(PYRIDIN-4-YL)PROPAN-1-ONE

4722

GLUTAMYL-VALYL-GLYCINE
L-gamma-Glutamyl-L-valyl-glycine
N-(N-L-gamma-Glutamyl-L-valyl)-glycine

1-(2-HYDROXY-4-ISOBUTOXYPHENYL)-3(PYRIDIN-2-YL)PROPAN-1-ONE4723

1-(2-HYDROXY-4-METHOXYPHENYL)-3(PYRIDIN-2-YL)PROPAN-1-ONE

4709

4710

L-THREONINE(S)-Threonine[R-(R*,S*)]-2-Amino-3-hydroxybutanoic acid

4724

TRANS-4-TERT-BUTYLCYCLOHEXANOLtrans-1-tert-Butylcyclohexan-4-oltrans-p-tert-Butylcyclohexanol

4711

LUO HAN FRUIT CONCENTRATE
Luo han guo concentrate
Luo han kuo concentrate
Siraitia grosvenorii concentrate
Fructus momordicae concentrate
Buddha’s Fruit concetrate
Monk’s Fruit concentrate
Longevity Fruit concetrate
Rakanka concentrate4725

3-(1-((3,5-DIMETHYLISOXAZOL-4-YL)METHYL)-1H-PYRAZOL4-YL)-1-(3-HYDROXYBENZYL)-IMIDAZOLIDINE-2,4-DIONE
2,4-Imidazolidinedione, 3-[1-[(3,5-dimethyl-4-isoxazolyl)methyl]-1H-pyrazol-4-yl]-1-[(3-hydroxyphenyl)methyl]-4726

3-(1-((3,5-DIMETHYLISOXAZOL-4-YL)METHYL)1H-PYRAZOL-4-YL)-1-(3-HYDROXYBENZYL)-5,5DIMETHYLIMIDAZOLIDINE-2,4-DIONE
2,4-Imidazolidinedione, 3-[1-[(3,5-dimethyl4-isoxazolyl)methyl]-1H-pyrazol-4-yl]-1-[(3hydroxyphenyl)methyl]-5,5-dimethyl-

4727

CLOVER HERB DISTILLATE
Yellow sweet clover distillate
Sweet clover distillate
Melilotus officinalis distillate

4712

L-ALANYL-L-GLUTAMINE
Glutamine, N2-L-alanyl-

4713

SUCROSE MONOPALMITATE
alpha-D-glucopyranoside, monohexadecanoate
beta-D-fructofuranoside, monohexadecanoate

07.11 • www.ift.org

57 pg

GRAS FLAVORING SUBSTANCES 25

Table 2 Average Usual Use Levels/Average Maximum Use Levels

Average Usual Use Levels (ppm)/Average Maximum Use Levels (ppm) for new FEMA GRAS Flavoring Substances on which the
FEMA Expert Panel based its judgments that the substances are generally recognized as safe (GRAS)

2-Methyl-5vinylpyrazine

2(4)-Ethyl4(2),6dimethyldihydro1,3,5-dithiazine(mixture ofisomers)(2E,6E/Z,8E)N-(2Methylpropyl)2,6,8decatrienamide

4-Amino-5,6dimethylthieno[2,3d]pyrimidin2(1H)-one

1,1Propanedithiol

Z-5-Octenyl
acetate(E)-4UndecenaldeltaHexadecalactone

Trilobatin

FEMA NO. 2566

3211

4667

4668

4669

4670

4671

4672

4673

4674

B aked Goods

0.3/3

4/9

0.5/1

5/10

0.01/0.05

8/10

0.05/0.1

10/50

Beverages(Non-alcoholic)

0.1/1

0.1/2

15/30

7.5/156/8

0.05/0.08

10/50

100/100

1/3

12.5/30

7.5/15

15/30

10/20

5/25

100/100

2-Hexyl-4acetoxytetrahydrofuran

CATEGORY

Beverages(A lcoholic)
Breakfast Cereal

0.5/1

Cheese0.5/1

Chewing Gum
0.5/1

Confectionery
Frostings

0.01/0.05

8/10

0.05/0.08

0.01/0.05
100/250

Condiments/
Relishes

0.08/0.1

10/50

5/15
35/75

2/10
10/12

0.08/0.1

0.01/0.05

2/10

10/25

0.05/0.08

10/50

0.08/0.1

10/50

Egg P roducts
Fats/Oils

1/2

Fish P roducts
Frozen Dairy

0.02/0.08

9/11

5/15
0.3/3

12.5/25

7.5/158/10

12.5/25

7.5/158/10

0.05/0.08

1/3

12.5/20

5/10

8/10

0.05/0.08

Fruit Ices
Gelatins/P uddings

2/10

2/5

Granulated Sugar

10/50
2/10

8/10

Gravies

0.5/1

Hard C andy

0.01/0.05
115/175

Imitation Dairy

0.5/1

10/25
7.5/15

12.5/25

Meat P roducts

1/2

Milk P roducts

0.5/1

0.08/0.1

8/10

0.05/0.08

0.02/0.08

Instant C offee /Tea
Jams/Jellies

10/50
8/10

10/25

10/50
8/10

0.02/0.08
7.5/150.01/0.05

50/2500.05/0.08
0.05/0.08

8/10

2/10
10/50

Nut P roducts
O ther Grains
P oultry

0.5/1

P rocessed Fruits

0.02/0.08
2.5/10

P rocessed
Vegetables

0.05/0.08

2/10

8/10

0.5/1

0.01/0.05

0.05/0.08

Reconstituted
Vegetables
Seasonings/
Flavors

1/10

Snack Foods
Soft C andy

1/2
0.3/3

4/9

Soups

0.5/1

12.5/255/15

0.08/0.1

25/50

5/15

0.02/0.08

115/150

10/25

7.5/150.01/0.05

Sugar Substitutes

300/600

Sweet Sauces

10/25

pg 58

07.11 • www.ift.org

8/10

0.05/0.08

8/10

0.05/0.08

50/25020/100

8/10
8/10

5/25
0.05/0.08

250/750

Arachidonic
acid enrichedoil

5-Isopropyl2,6-diethyl-2methyltetrahydro2H-pyran(1R,2S,5R)-N(4-Methoxyphenyl)5-methyl2-(1-methylethyl)-cyclohexanecarboxamide

Octahydro4,8a-dimethyl4a(2H)naphthol

2-Methyl-4,5dihydrofuran3-thiol(2S,5R)-N[4-(2-Amino2-oxoethyl)
phenyl]-5methyl-2(propan-2-yl)cyclohexanecarboxamide

4681

4682

4683

4684

L-Isoleucine

1-(2Furfurylthio)propanone(±)-4-Methyl2-propyl-1,3oxathiane

N-(2Methylcyclohexyl)2,3,4,5,6pentafluorobenzamide

4675

4676

4677

4678

4679

4680

B aked Goods

50/50

1/3

0.4/1

10/20

1/10

5/25

1/5

0.1/4

Beverages(Non-alcoholic)200/250

1/2

0.4/1

1/5

1/10

1/5

1/5

Beverages(A lcoholic)

50/50

1/2

0.2/1

4/20

1/10

1/5

Breakfast Cereal

50/50

1/10

1/5

CATEGORY

0.1/1

Cheese5/50

Chewing Gum

0.3/1

10/20

Condiments/
Relishes
2/5

0.3/1

500/2,000

1/5

0.1/1
0.1/1

100/500

1/10

Confectionery
Frostings

10/50

400/800

1/2.5
0.1/1

2/20

1/10

1/5

Egg P roducts

2/20

1/10

0.1/1

Fats/Oils

2/20

1/10

Fish P roducts

25/100

0.1/1
0.1/1

Frozen Dairy
Fruit Ices

0.1/1

Gelatins/P uddings

1/5

20/100

5/20

0.1/1

1/5

10/50

2/20

1/5

1/5

10/50

2/20

1/5

10/50

2/20

0.1/1

10/50

2/20

1/3

Granulated Sugar
Gravies

2/5

0.1/1

Hard C andy

1/2

0.1/1

10/50
1/5

Imitation Dairy

1/10

Instant C offee /Tea

2/5

Jams/Jellies

0.1/1

Meat P roducts

50/50

Milk P roducts

50/50

2/5

0.1/1

25/100

5/10

1/5

0.1/1

1/5

2/10

1/5

0.1/1

5/10

10/50

2/20

1/3
0.1/1

0.3/3

2/10

1/5

0.1/1

0.05/0.2

0.1/1

10/50
1/5

1/10

Nut P roducts

20/1000.1/1

O ther Grains

0.1/1

P oultry

0.1/1

10/100

P rocessed Fruits

0.2/1

P rocessed
Vegetables

0.2/1

1/5

0.1/1
2/10

1/5

0.1/1
0.1/1

Reconstituted

0.1/1

vegetables

Seasonings/
Flavors

0.2/1

Snack Foods

1/3

Soft C andy
Soups

0.2/1
0.1/1

50/50

10/50
10/50
1/5

1/2

10/50

Sugar Substitutes
Sweet Sauces

10/50

1/5

1/3

0.2/1

0.1/1

3/10

3/50

1/20

1/3

4/50

1/20

0.1/1

3/50

1/20

0.1/1

20/100

0.3/2

0.1/1

07.11 • www.ift.org

59 pg

GRAS FLAVORING SUBSTANCES 25

Table 2 continued- Average Usual Use Levels/Average Maximum Use Levels

Average Usual Use Levels (ppm)/Average Maximum Use Levels (ppm) for new FEMA GRAS Flavoring Substances on which the
FEMA Expert Panel based its judgments that the substances are generally recognized as safe (GRAS)(±)-6Octyltetrahydro-2Hpyran-2-one(±)-2-Methyltetrahydrofuran-3-thiol
acetate(±)-3-Hydroxy3-methyl-2,4nonanedione

1,1-Dipropoxyethane

Chrysanthemum
extract

Honeysuckle
extract

4688

4689

4690

CATEGORY

4685

4686

4687

B aked Goods

0.5/5

0.1/0.5

5/20

Beverages(Non-alcoholic)

0.1/2

0.01/0.03

1/3

Beverages(A lcoholic)0.02/0.05

5/20

Breakfast Cereal

0.01/0.03

2/10

Cheese0.1/0.2

5/20

Chewing Gum

0.01/0.03

10/20

Condiments/
Relishes

0.01/0.03

Confectionery
Frostings

0.01/0.03

Egg P roducts

0.01/0.03

Fats/Oils

0.01/0.03

Fish P roducts

0.01/0.03

Frozen Dairy

0.01/0.03

24/50

100/200

N-Cyclopropyl5-methyl-2isopropylcyclohexanecarboxamide

4691

4692

4693

0.06/0.6

50/1,000

0.002/0.015

100/200

50/2000.2/2

100/200

100/200

0.005/0.05

0.01/0.03

1/3

100/200

0.003/0.02

1/3

100/200

0.006/0.05

0.01/0.03

1/5

0.01/0.03

5/30

0.01/0.03

1/3

Imitation Dairy

1/10

Instant C offee /Tea

100/200
20/40

Jams/Jellies

0.02/0.05

1/3

Meat P roducts

0.02/0.05

2/5

0.01/0.04

5/30

Milk P roducts

0.5/5

Nut P roducts

0.01/0.03

O ther Grains

0.01/0.03

70/20050/1,000
100/200

0.01/0.025

100/200

0.01/0.025

100/200

0.06/0.2

10/30
0.01/0.1
50/1,000

100/200

P oultry

0.02/0.05
0.01/0.03

P rocessed
Vegetables

0.01/0.03

Reconstituted
Vegetables

0.01/0.03

Seasonings/
Flavors

0.01/0.03

100/2,000

50/200Snack Foods

0.01/0.03

5/20

50/200100/200

0.006/0.12

Soft C andy

0.01/0.03

1/5

50/200100/200

0.015/0.2

Soups0.01/0.03

1/10

50/200

Sugar Substitutes

0.01/0.03

Sweet Sauces0.02/0.05

07.11 • www.ift.org

0.01/0.1
100/400

50/1,000

P rocessed Fruits

pg 60

20/1001/5

0.02/0.05

Hard C andy

0.01/0.1

0.1/0.3

Fruit Ices

0.01/0.03

1,200/4,000

0.01/0.03

Gelatins/P uddings

0.01/0.03

10/40

50/1,000
400/400

1/5

Granulated Sugar

4694
0.01/0.1

100/200

5/30

Gravies

3-Pentanethiol

0.004/0.03

50/200
1/5

L-Methionylglycine

Yuzunone

100/200

0.01/0.1

0.003/0.02
100/200

1/10

50/200100/200

0.03/0.12

50/1,000

0.02/0.1

50/1,000

0.01/0.1

50/1,000

0.01/0.1
100/300

50/1,000

0.01/0.1

CATEGORY

2-Ethyl-2,5dihydro-4methylthiazole

1-(Methyldithio)-2propanone

5-Methylfurfurylmercaptan

4-Mercapto3-methyl2-butanol

FerrousL-lactateo-transCoumaric acid3-[(4-Amino2,2-dioxido1H-2,1,
3-benzothiadiazin5-yl)oxy]2,2-dimethyl-Npropylpropanamide

4695

4696

4697

4698

4699

4700

4701

4702

4703

4704

20/30

10/22

B aked Goods

0.5/1

Beverages(Non-alcoholic)0.1/0.5

Beverages(A lcoholic)0.1/0.5

0.2/0.50.005/0.05

Breakfast Cereal
Chewing Gum
Condiments/
Relishes

15.2/24.3

13/17

10/15

3.63/7.13

4/8

10/30

10/15

2/4

0.1/0.3

15/22

0.2/0.5

20/200Confectionery
Frostings

10/30

Egg P roducts

10/100Fats/Oils

10/100Fish P roducts

10/100

10/15
10/15

20/50
0.5/1

beta-Naphthyl
methyl ether

10/15

10/1000.2/0.5

Cinnamylbenzoate

10/30

20/30

Cheese2(3),5Dimethyl6,7-dihydro5H-cyclopentapyrazine

30/300

10/15

3/22

10/15

10/22

10/15

9/14

20/25

Frozen Dairy

0.1/0.5

10/30

5/22

Fruit Ices

0.1/0.5

10/30

5/22

10/15

Gelatins/P uddings

0.1/0.5

10/30

5/22

12/18

Granulated Sugar

10/15

5/10

8/10

10/20

9/11

10/15

Gravies0.1/0.5

Hard C andy

0.1/0.5

0.5/1

0.2/0.5

20/200

15/20
10/30

15/75

Imitation Dairy

20/25

3/3

10/15

Instant C offee /Tea

0.005/0.05

10/30

Jams/Jellies
Meat P roducts

0.5/1

0.2/0.5

10/15
10/22

10/15

3/22

10/15

20/200Milk P roducts

2/5
5/20

Nut P roducts

10/15

O ther Grains

10/15

P oultry

0.5/1

0.2/0.5

0.5/1

0.2/0.5

20/200

P rocessed Fruits
P rocessed
Vegetables
Reconstituted
Vegetables
Seasonings/
Flavors

10/15
0.1/0.5

Snack Foods

0.5/1

0.2/0.5

20/2000.5/1

0.2/0.5

20/200Soft C andy
Soups

10/15
10/30

0.1/0.5

Sugar Substitutes
Sweet Sauces

10/15

0.1/0.5

0.5/1

0.2/0.5

20/200

15/75

10/15

10/20

10/15

10/30

10/15
10/22

9/18

12/14

10/15

07.11 • www.ift.org

61 pg

GRAS FLAVORING SUBSTANCES 25

Table 2 continued- Average Usual Use Levels/Average Maximum Use Levels

Average Usual Use Levels (ppm)/Average Maximum Use Levels (ppm) for new FEMA GRAS Flavoring Substances on which the
FEMA Expert Panel based its judgments that the substances are generally recognized as safe (GRAS)

Glutamylvalyl-glycine

4707

4708

4709

4710

4711

4712

4713

4714

0.1/5

50/30050/20040/60

1,400/3,000

4/100

0.1/0.5

5/25

50/50050/20040/60

60/6000.2/500.1/0.5

10/50

100/500

50/20040/60

60/6000.2/500.1/0.5

50/40050/20040/80

0.1/0.5

50/40050/2009-Decen-2-one

CATEGORY

4705

4706

B aked Goods

20/2,000

Beverages(Non-alcoholic)

20/2,000

Beverages(A lcoholic)

20/2,000

1-(Methylthio)3-octanone

Breakfast Cereal
Cheese0.1/5

Chewing Gum

30/150Condiments/
Relishes

50/60030/15050/300

Egg P roducts

0.1/5

Fats/Oils

0.1/5

Fish P roducts

L-Threonine

Luo han fruit
concentrate

50/2000.1/5

Confectionery
Frostings

Ethyl2-mercapto2-methylpropionate

3',7-Dihydroxy4'methoxyflavan

Rosemaryoleoresin

L-Alanyl-Lglutamine

Sucrosemonopalmitate

600/3,000

0.1/100

1,400/3,000

0.1/100

100/500

0.5/5050/2005/40

2,000/5,000

5/100

50/20040/80

300/500

0.5/501,000/2,000

0.1/5050/20050/30050/200200/600

0.1/5050/30050/2001,000/2,500

0.1/100

0.1/0.5

0.1/0.5

Frozen Dairy

5/15

50/30050/2005/80

1,400/3,000

0.1/300.1/0.5

Fruit Ices

5/15

50/40050/2005/40

200/600

0.1/500.1/0.5

50/30050/20040/80

200/500

0.1/50Gelatins/P uddings
Granulated Sugar

20/50

50/40050/20050/50050/2001,400/3,000

0.1/500.1/0.5

Hard C andy

50/50050/20040/80

200/600

0.1/5

0.1/0.5

Imitation Dairy

50/50050/2005/40

1,400/3,000

0.5/5

Instant C offee /Tea

50/40050/200300/600

0.1/500.1/0.5

Jams/Jellies

50/50050/20010/40

300/500

0.1/100

0.1/0.5

50/30050/2001,400/3,000

0.1/100

Gravies

Meat P roducts

0.1/5

20/2,000

Milk P roducts

0.1/5
10/30

50/40015/45

Nut P roducts
O ther Grains

50/20040/80

1,400/3,000

0.5/200

50/2005/40

300/1,000

0.1/100

50/200300/2,000

0.1/500.1/5

50/2001,000/2,000

0.1/5060/300

0.1/5

P rocessed
Vegetables

0.1/5

50/200300/500

0.1/50Reconstituted
Vegetables

0.1/5

50/200200/400

0.1/50P oultry
P rocessed Fruits

Seasonings/
Flavors
Snack Foods

10/30

20/2,000
10/50

50/2000.1/5

50/6000.1/5

50/500Soft C andy

30/60

50/300

Soups

0.1/5

50/30020/50

50,000/100,000

5/40

20,000/250,000

0.1/5050/2005/40

2,000/5,000

0.1/5050/20040/80

0.1/0.5

200/600

0.1/500.1/0.5

1,000/5,000

0.1/200

0.1/0.5200/1,000

0.1/10200/500

0.5/5050/30050/200

Sweet Sauces

50/40050/20007.11 • www.ift.org

0.1/0.5

50/200

Sugar Substitutes

pg 62

5/40

0.1/0.5

5/40

0.1/0.5

2-(3,4Dihydroxyphenyl)5,7dihydroxy-4chromanon

N-[N-[3-(3Hydroxy-4methoxyphenyl)
propyl]L-alphaaspartyl]-Lphenylalanine
1-methylester,monohydrate

Sweet
blackberryleaves extract

2-[2(p-Menthyloxy)ethoxy]
ethanol

CATEGORY

4715

4716

4717

4718

B aked Goods

20/100Beverages(Non-alcoholic)

20/150Beverages(A lcoholic)

20/100

Breakfast Cereal

20/1001/2

330/425

1/10

60/20060/20050/25040/50

330/425

20/10010/10060/2001/10

60/20010/10060/200100/250trans-4-tertButylcyclohexanol

4722

4723

4724

1/2

2/25

5/35

20/50
20/50

200/400

5/35
5/25

1,000/1,000
2/5

2/25

20/10050/20060/2000.5/5

Fish P roducts

60/20020/10060/20020/100

0.9/1

Fruit Ices

330/425

1/10

60/200330/425

1/10

60/2000.5/5

60/2000.5/5

60/2001/10

60/20020/100Granulated Sugar

2/5

2/2

5/30

5/25

5/30

60/200

Gravies
Hard C andy

20/100Imitation Dairy

20/100Instant C offee /Tea

20/100330/425

0.1/1

60/2001/10

60/200Meat P roducts

5/25
20/50
50/30060/20020/1000.9/1

330/425

60/200

Nut P roducts

60/200O ther Grains

60/200P oultry

60/200

P rocessed Fruits

60/200

P rocessed
Vegetables

60/200Reconstituted

60/20020/10020/10060/200Jams/Jellies
Milk P roducts4721

1-(2-Hydroxy4-methoxyphenyl)3-(pyridin-2yl)-propan1-one

1-(2-Hydroxy4-isobutoxyphenyl)-3(pyridin-2-yl)
propan-1-one

60/200Fats/Oils

Gelatins/P uddings

4720

30/100

Egg P roducts

Frozen Dairy

4719

1/10

330/425

Condiments/
Relishes
Confectionery
Frostings

Rebaudioside C

60/200CheeseChewing Gum

Succinic acid

1-(2-Hydroxyphenyl)-3(pyridin-4-yl)
propan-1-one

5/20

5/25

5/20

5/5

20/100

5/35

20/50

vegetables

Seasonings/
Flavors

50/2001,000/10,000

100/1,000

5/10

5/50

20/100Snack Foods

20/1001/10

60/2005/10

5/25

20/1001/10

60/2001/10

60/2000.05/0.5

100/1,000

5/50

60/200Soft C andy
Soups

20/100

Sugar Substitutes

20/100

Sweet Sauces

20/100330/425

20/1005/20
5/25

07.11 • www.ift.org

20/10063 pg

GRAS FLAVORING SUBSTANCES 25

Table 2 continued- Average Usual Use Levels/Average Maximum Use Levels

Average Usual Use Levels (ppm)/Average Maximum Use Levels (ppm) for new FEMA GRAS Flavoring Substances on which the
FEMA Expert Panel based its judgments that the substances are generally recognized as safe (GRAS)

CATEGORY

3-(1-((3,5-Dimethylisoxazol4-yl)methyl)-1H-pyrazol4-yl)-1-(3-hydroxybenzyl)imidazolidine-2,4-dione

3-(1-((3,5-Dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)1-(3-hydroxybenzyl)-5,5dimethylimidazolidine-2,4-dione

4725

4726

B aked Goods
Beverages(Non-alcoholic)

4727
0.5/2

2/10

2/10

Beverages(A lcoholic)
Breakfast Cereal

Clover herb
distillate

0.3/0.8
0.5/2

20/60

20/60

0.5/2

Chewing Gum

300/1,200

300/1,200

Condiments/
Relishes

20/60

20/60

Confectionery
Frostings

20/60

20/60

0.5/2

Frozen Dairy

20/60

20/60

0.4/2

Fruit Ices

20/60

20/60

Gelatins/P uddings

20/60

20/60

Hard C andy

75/30075/300Imitation Dairy

2/10

2/10

0.4/1.6

Instant Coffee /Tea

2/10

2/10

0.3/1

CheeseEgg P roducts
Fats/Oils
Fish P roducts

0.4/2

Granulated Sugar
GraviesJams/Jellies

0.4/1

Meat P roducts
Milk P roducts

2/10

2/10

Nut P roducts

0.4/1.6
0.4/1.6

O ther Grains
P oultry
P rocessed Fruits
P rocessed
Vegetables
Reconstituted

20/60

20/60

25/10025/100vegetables

Seasonings/
Flavors

0.2/1

Snack Foods

20/60

20/60

0.5/2

Soft C andy

75/30075/300

0.6/2

Soups

2/10

2/10

Sugar Substitutes

2/20

2/20

Sweet Saucespg 64

0.3/0.8

07.11 • www.ift.org

25

GRAS FLAVORING SUBSTANCES 25

Table 3 Updated Average Usual Use Levels/Average Maximum Use Levels
Average usual use levels (ppm)/average maximum use levels (ppm) for flavoring substances
previously recognized as FEMA GRAS. Superscript ‘a’ represents a new use level.

Capiscum oleoresin

Sodium acetate

L-Glutamic acid

GlycineEthyl-2-isopropyl-5methylcyclo-hexanecarboxamide

FEMA NO.

2234

3024

3285

3287

3455

GRAS PUBLICATION

3

3

5

5

9

B aked Goods

50/85

15/15

1,400 a/3,000a

50/150Beverages(Non-alcoholic)90/105

1.5/1.5

400/600 a

250a/1,000

Beverages (A lcoholic)800/900

1.5/1.5

60a/600a

Breakfast Cereal

25a/50a0.01/60

600a/3,000a

CATEGORY

Cheese1,400 a/3,000a

Chewing Gum

450 /500

Condiments/Relishes

250/330

2,000 a/5,000a

Confectionery Frostings

20a/50a300a/500aa

100 a/500aa

Egg P roducts
Fats/Oils

1,000 /2,000a

100 a/125a

1/5

150/15010/10a1,000 a/2,500 a
25a/28 a

Fruit Ices
Gelatins/P uddings

1,400 a/2,000 a

200 a/600a

Fish P roducts
Frozen Dairy

10/10
10/10

15/15

1,400 a/3,000

10/10

15/15

200 a/600a

10/10

200 /500

10/10

18/20

a

a

Granulated Sugar
Gravies

49/50aHard C andy

100 a/150a

Imitation Dairy

15 /25

Instant Coffee /Tea

10a/15aJams/Jellies

15 /25Meat P roducts

75/145

Milk P roducts

15a/25aNut P roducts

50 /100

O ther Grains

25 /40aa

200 a/600a
1,400 /3,000aa25/150100/150 a

10/10

a

300a/600aaaa1,400 a/3,000a
200/200

0.32/0.32

300a/500a

50/1501,500 a/2,500 a

1,400 a/3,000a

150/150

1,400 a/3,000a
15,000 / 30,000

a

a

6/6

a

a

300a/1,000 a
300 a/2,000 a

P oultry

1,000 a/2,000 a

P rocessed Fruits

15a/50a60a/300a

P rocessed Vegetables

20a/25a

300a/500a

Reconstituted Vegetables

200 a/400 a

Seasonings/Flavors

100 /200

Snack Foods

50 /100

Soft C andy

100 a/200 a

0.88/0.9200 a/600a

25/150Soups

25a/50a0.1/0.5

1,000 a/5,000a

150/150aaaSugar Substitutes
Sweet Saucesa1,500 /3,000aa

15,000/30,000

20,000 a/250,000 a
2,000 a/5,000a

66 a/100 a

200 a/1,000 a
50 /75aa

200 a/500a

07.11 • www.ift.org

65 pg

GRAS FLAVORING SUBSTANCES 25

Table 3 continued- Updated Average Usual Use Levels/Average Maximum Use Levels
Average usual use levels (ppm)/average maximum use levels (ppm) for flavoring substances
previously recognized as FEMA GRAS. Superscript ‘a’ represents a new use level.

Vanillyl butyl ether

Neohesperidine
dihydrochalcone

L-Alanine

L-Arginine

L-Lysine

FEMA NO.

3796

3811

3818

3819

3847

GRAS PUBLICATION

16

17

18

18

18

B aked Goods

5/20

5a/20 a75/3751,400 a/3,000a

1,400 a/3,000a

Beverages(Non-alcoholic)

8 a/20 a

5/15a

400 a/500a

60a/600a60a/600a

Beverages (A lcoholic)

30 /80a5/15

a50/15060 /600

Breakfast Cereal

60 /100

8 /20

50/150600 /3,000

Cheese100 /200

10/20

1,400 /3,000

Chewing Gum

CATEGORY

pg 66

a

a

a

a

a

a

a

3/4

a

60a/600aaa600a/3,000a

a

a

a

1,400 a/3,000a

3,500 a/4,200 a

200/300 a

5/10

100 a/500a

100 a/500a

Condiments/Relishes

40a/75a2/3

20/1002,000 a/5,000a

2,000 a/5,000a

Confectionery Frostings

70a/100 a

3/3

25/100300a/500a

300a/500a

Egg P roducts

5/10

2/3

50/2501,000 /2,000

Fats/Oils

200 /300

4/4

10/30

200 /600

Fish P roducts

200 a/250a

2/3

50/2501,000 a/2,500 a

1,000 a/2,500 a

Frozen Dairy

100 a/150a

2/8 a

60/2001,400 a/3,000a

1,400 a/3,000a

Fruit Ices

35a/50a2 a/3a

10/20

200 a/600a

200 a/600a

Gelatins/P uddings

70 /100a

3/8

50/150200 /500

200 a/500a

Granulated Sugar

50 /100aGravies

10a/20 a

3/4

Hard C andy

400 a/700a

a

a

a

a

a

a

a

a

200 a/600a

a

a

5/10

1/20

5/25

200/1,000

1,400 a/3,000a

1,400 a/3,000a
200 a/600a

5/15

50/200200 a/600a

Imitation Dairya90 /110

a

3/10

a

50/1501,400 /3,000

Instant Coffee /Tea

15 /30a3 /6

a100/500

300 /600aa1,000 a/2,000 a

a

a

a

1,400 a/3,000aa300a/600a

a

Jams/Jellies

35a/50a

2/3

5/10

300 a/500a

300a/500a

Meat P roducts

10a/20 a

2/3

100/500

1,400 a/3,000a

1,400 a/3,000a

Milk P roducts

25a/50a3/10a50/1501,400 a/3,000a

1,400 a/3,000a

Nut P roducts

200 /500

300a/1,000 a

3/4

75/225300 /1,000a

O ther Grains

60 /100

a

3/4

10/20

300 /2,000a300a/2,000 a

P oultry

100 a/250a

2/3

100/500

1,000/2,000 a

1,000 a/2,000 a

P rocessed Fruits

5a/25a2/3

10/30

60a/300a60a/300a

P rocessed Vegetables

5/25

a

2/3

300a/500a

Reconstituted Vegetables

5/10

Seasonings/Flavors

10 /20

a

a

a

a

a

a

a

5/10

a

300 /500

a

2/3

5/10

200 /400a

3/4

2,000/4,000

20,000 /250,000a

200 a/400 aaa

20,000 a/250,000 a

Snack Foods

25a/65

3/3

100/200

2,000 a/5,000a

2,000 a/5,000a

Soft C andy

400 a/500a

4 a/10a25/100200 a/600a

200 a/600a

Soups

30 /45a

5/10

100/500

1,000 /5,000

Sugar Substitutesa40 /55

a

4/4

10/20

200 /1,000

Sweet Sauces

65 /80a

2/3

25/100200 /500

07.11 • www.ift.org

a

a

a

a

a

a

a

a

1,000 a/5,000a
200 a/1,000 a
200 a/500a

Sodium diacetate

p-Menthane-3,8-diol

N1-(2,4Dimethoxybenzyl)-N2-(2(pyridin-2-yl)ethyl)oxalamide

gamma-Octadecalactonedelta-Octadecalactone

FEMA NO.

3900

4053

4233

4446

4447

GRAS PUBLICATION

18

21

22

24

24

CATEGORY
B aked Goods

100 a/120a

1/2

5/20 a0.5/10a

Beverages(Non-alcoholic)

48 a/50a1a/2 a1a/10a0.1/1

Beverages (A lcoholic)

40 /50

Breakfast Cereal

20a/50a5a/10aCheese50a/75a1/3

aChewing Gum

0.1/1

a

Condiments/Relishes

50a/100 a

Confectionery Frostings

200 a/350a
1a/2 aFats/Oils

100 /500aaFish P roducts

5/10

5/25

Fruit Ices

5a/20 a0.1/10 a

5/25

Gelatins/P uddings

150a/200 a

Granulated Sugar

5a/25aGravies

35a/40 a

Hard C andy

500a/800a

Imitation Dairy

75a/100 a

Instant Coffee /Tea

25a/50a

Jams/Jellies

2/4

0.1/3

150a/175a
1,500 a/ 2,500 a

Milk P roducts

1/3
75 /100a

15,000/30,000a

15 /50a

O ther Grains
P oultry

2/4
1/3

Frozen Dairy

Nut P roducts

0.5/3
2/4

Egg P roducts

Meat P roducts

5/10

1,500 a/2,000 a

1 /2
a

5/10

0.1/10 a

5/20

2 a/20 aa

1a/2 a1,500 a/2,500 a

1/3

P rocessed Fruits

20a/150a

P rocessed Vegetables

20a/75a

1/3

Reconstituted Vegetables

20a/25a1a/2 aSeasonings/Flavors

15,000a/30,000a

15a/30a5/10

Snack Foods

15,000/30,000

15a/30a5/10Soft C andy

500a/750a

Soups

15a/25a

2/4

0.1/1

Sugar Substitutes
Sweet Sauces

25a/300a07.11 • www.ift.org

67 pg

GRAS FLAVORING SUBSTANCES 25

Table 4 Updated Average Usual Use Levels/Average Maximum Use Levels in Chewing Gum
Updated average usual use levels (ppm)/average maximum use levels (ppm) in chewing
gum for flavoring substances previously recognized as FEMA GRAS

FEMA NO.

Primary Name

Anticipated Usual
Use Level (ppm)

AnticipatedMaximum Use
Level (ppm)

FEMA NO.

Primary Name

Anticipated Usual
Use Level (ppm)

AnticipatedMaximum Use
Level (ppm)

2003

ACETALDEHYDE

70

1,000

2152

BENZYL ISOVALERATE

1

5

2004

PROPYL PHENETHYL ACETAL

50

70

2160

ISOBORNYL ACETATE

100

100

2005

ACETANISOLE

150

1,060

2167

9

ACETIC ACID

400

5,000

BORONIA ABSOLUTE (BORONIAMEGASTIGMA NEES (RUTACEAE))

2

2006
2008

ACETOIN

25

110

2177

ISOBUTYL ACETOACETATE

55

180

2011

ADIPIC ACID

500

4,040

2178

BUTYL ALCOHOL

160

400

10

2179

ISOBUTYL ALCOHOL

50

500

2185

ISOBUTYL BENZOATE

15

35
100

2019

ALLSPICE OLEORESIN (PIMENTA
OFFICINALIS LINDL. (MYRTACEAE))

5

2021

ALLYL BUTYRATE

5

10

2187

ISOBUTYL BUTYRATE

3

2025

ALLYL CYCLOHEXANEHEXANOATE

20

25

2188

BUTYL ISOBUTYRATE

5

10

2033

ALLYL ALPHA-IONONE

1

1

2189

ISOBUTYL ISOBUTYRATE

1

2,000

2038

ALLYL PHENOXYACETATE

5

10

2045

ALLYL ISOVALERATE

5

10

2050

AMBRETTE ABSOLUTE OIL (HIBISCUS
ABELMOSCHUS L. (MALVACEAE))

1

5

2190

BUTYL BUTYRYLLACTATE

25

50

2197

ISOBUTYL FORMATE

60

125

2201

BUTYL HEXANOATE

1

3

2205

BUTYL LACTATE

10

10

2054

AMMONIUM ISOVALERATE

300

2,700

2061

ALPHA-AMYLCINNAMALDEHYDE

360

460

2206

BUTYL LAURATE

0.3

0.5

2067

ALPHA-AMYLCINNAMYL ISOVALERATE

1

2

2208

ALPHA-ISOBUTYLPHENETHYL
ALCOHOL

1

8

2213

ISOBUTYL SALICYLATE

45

50

2215

BUTYL SULFIDE

1

5

2216

BUTYL 10-UNDECENOATE

0.1

1

2217

BUTYL VALERATE

500

1,300

2219

BUTYRALDEHYDE

4

6

2220

ISOBUTYRALDEHYDE

40

200

2221

BUTYRIC ACID

50

300

2222

ISOBUTYRIC ACID

12

100
250

2074

AMYL HEXANOATE

35

1,000

2080

ISOAMYL OCTANOATE

1

100

2081

ISOAMYL PHENYLACETATE

100

215

2084

ISOAMYL SALICYLATE

85

240

2086

TRANS-ANETHOLE

880

6,680

2087

ANGELICA ROOT EXTRACT (ANGELICA
ARCHANGELICA L. (APIACEAE))

60

60

2093

ANISE (PIMPINELLA ANISUM
L. (APIACEAE))

1

5

2096

ANISE, STAR, OIL (ILLICIUM
VERUM HOOK, F. (APIACEAE))

80

470

2223

(TRI-)BUTYRIN

250

2097

ANISOLE

1

5

2228

CALCIUM ACETATE

0.2

0.5

2099

ANISYL ALCOHOL

1

50

2229

CAMPHENE

5

400

2100

ANISYL BUTYRATE

3

5

2230

D-CAMPHOR

160

500

2101

ANISYL FORMATE

25

70

2231

2

7

2108

ASAFOETIDA OIL (FERULAASAFOETIDA L. (UMBELLIFERAE))

1020

CAMPHOR, JAPANESE, WHITE,OIL (CINNAMOMUM CAMPHORA(L.) NEES ET EBERM.)

2114

BALSAM FIR, OIL – ABIES BALSAMEA(L.) MILL.(PINACEAE))

5

25

2233

CAPSICUM EXTRACTCAPSICUM FRUTESCENS L.
CAPSICUM ANNUUM L.

50

125

2115

BALSAM FIR, OLEORESIN – ABIESBALSAMEA (L.) MILL. (PINACEAE)

2

2

2248

4-CARVOMENTHENOL

150

1,500

2251

CARVYL PROPIONATE

25

60

2255

CASCARILLA BARK, OIL –CROTON CASCARILLA BENN.
AND C. ELUTERIA BENN.

1

1

2118

BASIL (OCIMUM BASILICUM
L. (LAMIACEAE))

5

15

2125

BAY OIL, SWEET (LAURUSNOBILIS L. (LAURACEAE))

10

10

2130

BENZALDEHYDE PROPYLENE
GLYCOL ACETAL

4

50

2256

CASSIA (CINNAMOMUM CASSIABLUME)(LAURACEAE)

175

1,000

2257

CASSIA BARK EXTRACT(CINNAMOMUM CASSIABLUME (LAURACEAE))

5

10

2268

CASSIA BARK, EXTRACT –CINNAMOMUM CASSIA BLUME

1

10

2269

CELERY SEED EXTRACT (APIUMGRAVEOLENS L. (APIACEAE))

1

1

2134

BENZOPHENONE

115

500

2136

BENZYL ACETOACETATE

220

1,160

2141

BENZYL ISOBUTYRATE

10

15

2150

BENZYL PROPIONATE

90

150

2151

BENZYL SALICYLATE

5

30

pg 68

07.11 • www.ift.org

Anticipated Usual
Use Level (ppm)

AnticipatedMaximum Use
Level (ppm)

CELERY SEED EXTRACT SOLID (APIUMGRAVEOLENS L. (APIACEAE))

1

1

CHAMOMILE FLOWER, ENGLISH, OIL(ANTHEMIS NOBILIS L. (COMPOSITAE))

1

FEMA NO.

Primary Name

2270
2272
2287

CINNAMALDEHYDE ETHYLENE
GLYCOL ACETAL

2

1
300

FEMA NO.

Primary Name

Anticipated Usual
Use Level (ppm)

AnticipatedMaximum Use
Level (ppm)

2360

GAMMA-DECALACTONE

50

225

2361

DELTA-DECALACTONE

15

100

2363

DECANAL DIMETHYL ACETAL

0.5

2

2366

2-DECENAL

5

10

2369

DECYL PROPIONATE

35

80

2288

CINNAMIC ACID

60

300

2374

DIETHYL MALATE

10

20

2289

CINNAMON [CINNAMOMUMZEYANICUM NEES; C. LOUREIRIIBLUME; C. CASSIA BLUME] –CEYLON CINNAMON; CHINESECINNAMON; SAIGON CINNAMON

1,000

1,000

2376

DIETHYL SEBACATE

675

1,270

2377

DIETHYL SUCCINATE

350

2,950

2380

DIHYDROCARVYL ACETATE

50

500

2293

CINNAMYL ACETATE

160

1,000

2381

DIHYDROCOUMARIN

20

250

2298

CINNAMYL CINNAMATE

20

400

2382

DILL (ANETHUM GRAVEOLENS(APIACEAE))

1

10

2299

CINNAMYL FORMATE

1

150

2384

10

CITRAL DIMETHYL ACETAL

0.1

0.5

DILL SEED, INDIAN – ANETHUM SOWA
ROXB. (PEUCEDANUM GRAVEOLENSBENTH. ET HOOK.; A. GRAVEOLENS L.)

1

2305

2388

ALPHA,ALPHA-DIMETHYLBENZYLISOBUTYRATE

30

500

2306

CITRIC ACID

10,00025,4002308

CITRONELLA OIL

10

30

2310

CITRONELLOXYACETALDEHYDE

5

15

2313

CITRONELLYL ISOBUTYRATE

25

115

2314

CITRONELLYL FORMATE

100

2389

2,6-DIMETHYL-5-HEPTENAL

240

5,000

2394

ALPHA,ALPHA-DIMETHYLPHENETHYL
BUTYRATE

10

500

210

2396

DIMETHYL SUCCINATE

50

300

2399

DITTANY OF CRETE (ORIGANUMDICTAMNUS L.)

10

42

2400

GAMMA-DODECALACTONE

40

100

2315

CITRONELLYL PHENYLACETATE

25

45

2316

CITRONELLYL PROPIONATE

5

10

2320

CLARY (SALVIA SCLAREA
L. (LAMIACEAE))

1

1

2321

CLARY OIL (SALVIA SCLAREA
L. (LAMIACEAE) )

3

10

2322

CLOVE BUD, EXTRACT – EUGENIACARYOPHYLLATA THUNB. [EUGENIA
AROMATICA (L.) BAILL.]

5080

CLOVE BUD, OLEORESIN – EUGENIA
CAROPHYLLATA THUNB. [EUGENIA
AROMATICA (L.) BAILL.]

95

2333

CORIANDER (CORIANDRUM
SATIVUM L. (UMBELLIFERAE))

1

1

2337

P-CRESOL

1

3

2339

CUBEB OIL (PIPER CUBEBA
L. F. (PIPERACEAE))

15

20

2324

2340

155

DELTA-DODECALACTONE

10

500

ELEMI, GUM – CANARIUM COMMUNE
L. OR C. LUZONICUM (MIQ.) A. GRAY

1

3

2408

ELEMI, OIL – CANARIUM COMMUNE
L. OR C. LUZONICUM (MIQ.) A. GRAY

5

50

2412

ESTRAGON OIL (ARTEMISIADRACUNCULUS L.(COMPOSITAE))

5

20

2413

P-ETHOXYBENZALDEHYDE

290

960

2415

ETHYL ACETOACETATE

170

1,500

2418

ETHYL ACRYLATE

100

500

2420

ETHYL P-ANISATE

3

10

2423

ETHYL BENZOYLACETATE

240

240

2426

2-ETHYLBUTYRALDEHYDE

1,000

5,000

2429

2-ETHYLBUTYRIC ACID

50

1,000

2431

ETHYL CYCLOHEXANEPROPIONATE

2

5
600

CUMIN (CUMINUM CYMINUM
L. (UMBELLIFERAE))

35

CURRANT BUDS BLACK
ABSOLUTE (RIBES NIGRUM
L. (GROSSULARIACEAE))

5

2349

CYCLOHEXYL ACETATE

1

1

2351

CYCLOHEXYL BUTYRATE

5

50

2352

CYCLOHEXYL CINNAMATE

1

25

2353

CYCLOHEXYL FORMATE

3

5

2448

ETHYL 2-NONYNOATE

5

10

2355

CYCLOHEXYL ISOVALERATE

120

400

2449

ETHYL OCTANOATE

30

500

2357

DANDELION, FLUID EXTRACT –TARAXACUM OFFICINALE WEBER;
T. ERYTHROSPERMUM ANDRZ.

5

30

2450

ETHYL OLEATE

1

10

2451

ETHYL PALMITATE

0.1

0.1

DANDELION ROOT, EXTRACT
SOLID – TARAXACUM OFFICINALE
WEBER; T. ERYTHROSPERMUM ANDRZ.

1

2452

ETHYL PHENYLACETATE

1

10

2453

ETHYL 4-PHENYLBUTYRATE

10

15

2346

2358

40

2401
2407

20

5

2432

ETHYL DECANOATE

35

2435

ETHYL 3(2-FURYL)PROPANOATE

1

5

2436

4-ETHYLGUAIACOL

5

15

2438

2-ETHYL-2-HEPTENAL

80

500

2442

ETHYL LEVULINATE

75

500

07.11 • www.ift.org

69 pg

GRAS FLAVORING SUBSTANCES 25

Table 4 continued- Updated Average Usual Use Levels/Average Maximum Use Levels in Chewing Gum
Updated average usual use levels (ppm)/average maximum use levels (ppm) in chewing
gum for flavoring substances previously recognized as FEMA GRAS

Anticipated Usual
Use Level (ppm)

AnticipatedMaximum Use
Level (ppm)

Anticipated Usual
Use Level (ppm)

AnticipatedMaximum Use
Level (ppm)

HEXANAL15

1,000

2,3-HEXANEDIONE

140

420

HEXANOIC ACID

100

1,000

2560

HEXEN-2-AL

65

1,000

2561

CIS-3-HEXENAL

5

100

2564

2-HEXEN-1-YL ACETATE (E)

100

1,000

2565

HEXYL ACETATE

150

1,300

2568

HEXYL BUTYRATE

100

5,000

2569

ALPHA-HEXYLCINNAMALDEHYDE

510FEMA NO.

Primary Name

1,300

2557

2,000

2558
2559

FEMA NO.

Primary Name

2455

ETHYL 3-PHENYLPROPIONATE

530

2458

ETHYL SALICYLATE

570

2459

ETHYL SORBATE

10

1,000

2460

ETHYL TIGLATE

40

250

2465

EUCALYPTOL

1,380

15,0002474

ISOEUGENYL FORMATE

5

10

2475

EUGENYL METHYL ETHER

40

250

2476

ISOEUGENYL METHYL ETHER

150

190

2477

ISOEUGENYL PHENYLACETATE

1

1

2478

FARNESOL

1

500

2571

HEXYL 2-FUROATE

90

235

2479

D-FENCHONE

10

100

2572

HEXYL HEXANOATE

320

500

2480

FENCHYL ALCOHOL

50

500

2575

HEXYL OCTANOATE

0.5

1

2481

FENNEL, COMMON(FOENICULUMVULGARE MILL. (APIACEAE))

5

10

2576

HEXYL PROPIONATE

1

2

2482

FENNEL, SWEET [FOENICULUMVULGARE MILL. VAR. DULCE (DC.)
ALEF.] – FINOCHIO; FLORENCE FENNEL

15

20

2582

HORSEMINT LEAVES,EXTRACT – MONARDA SPP.

10

43

2584

5

FENUGREEK (TRIGONELLA FOENUMGRAECUM L. (FABACEAE))

226

500

HYDROXYCITRONELLALDIETHYL ACETAL

1

2484
2486

FENUGREEK OLEORESIN (TRIGONELLA
FOENUMGRAECUM L. (FABACEAE))

300

600

2487

FORMIC ACID

450

650

2488

FUMARIC ACID

2,100

6,350

2490

FURFURYL ACETATE

95

375

2491

FURFURYL ALCOHOL

40

60

2492

2-FURFURYLIDENE BUTYRALDEHYDE

1

5

2493

FURFURYL MERCAPTAN

5

10

2501

GALBANUM, OIL – FERULAGALBANIFLUA BOISS. ET BUHSEAND OTHER FERULA SPP.

1

1

2505

GENET, EXTRACT [SPARTIUM
JUNCEUM L.]-BROOM, EXTRACT

1

10

2506

GENTIAN ROOT EXTRACT (GENTIANA
LUTEA L. (GENTIANACEAE))

10

70

2513

GERANYL ISOBUTYRATE

5

10

2515

GERANYL HEXANOATE

5

2522

GINGER OIL

35

2523

GINGER OLEORESIN (ZINGIBEROFFICINALE ROSC. (ZINGIBERACEAE))

1025

GRAINS OF PARADISE (AFRAMOMUMMELEGUETA (ROSC.) K. SCHUM.
(ZINGIBERACEAE))

760

2531

GUAIAC GUM, EXTRACT – GUAIACUM
OFFICINALE L.; G. SANCTUM L.

1

1

2533

GUAIAC WOOD, EXTRACT – GUAIACUM
OFFICINALE L.; G. SANCTUM L.;
BULNESIA SARMIENTI LORENTZ

10

120

2538

HAW BARK BLACK EXTRACT(VIBURNUM PRUNIFOLIUM
L.(CAPRIFOLIACEAE))

1

1

2539

GAMMA-HEPTALACTONE

1

2543

2,3-HEPTANEDIONE

2

5

2556

GAMMA-HEXALACTONE

50

400

2529

pg 70

07.11 • www.ift.org

2586

HYDROXYCITRONELLOL

25

50

2587

5-HYDROXY-4-OCTANONE

30

500

2593

INDOLE

40

350

2597

ALPHA-IRONE

2

5

2601

JASMINE SPIRITUS (JASMINUM
GRANDIFLORUM L.(OLEACEAE) )

1

9

2604

JUNIPER OIL (JUNIPERUS
COMMUNIS L. (CUPRESSACEAE))

1

1

2607

KOLA NUT, EXTRACT – COLAACUMINATA SCHOTT ET ENDL.

7

50
2,160

2611

LACTIC ACID

290

2614

LAURIC ACID

2

5

2616

LAURYL ACETATE

50

100

2622

LAVENDER, OIL – LAVANDULA
OFFICINALIS CHAIX

3

5

2630

LICORICE ROOT (GLYCYRRHIZA
GLABRA L. (LEGUMINOSAE))

30

3,000

10

2640

LINALYL ISOBUTYRATE

5

100

190

2645

LINALYL PROPIONATE

20

100

2646

LINALYL ISOVALERATE

1

100

2649

LOVAGE (LEVISTICUM OFFICINALE
KOCH (UMBELLIFERAE))

5

32

2650

LOVAGE EXTRACT (LEVISTICUM
OFFICINALE KOCH (UMBELLIFERAE))

10

100

2652

MACE (MYRISTICA FRAGRANSHOUTT. (MYRISTICACEAE))

2

9

2655

L-MALIC ACID

6,000

25,0002660

MARJORAM, POT – ORIGANUMVULGARE L.

70

70
2,000

765

5

2666

(+)-NEOISOMENTHOL

500

2667

MENTHONE

1,000

6,000

2668

MENTHYL ACETATE (ISOMERUNSPECIFIED)

500

2,000

2671

2-METHOXY-4-METHYLPHENOL

15

25

Anticipated Usual
Use Level (ppm)

AnticipatedMaximum Use
Level (ppm)

4-(P-METHOXYPHENYL)2-BUTANONE

50

500

1-(P-METHOXYPHENYL)1-PENTEN-3-ONE

1

FEMA No.

Primary Name

2672
2673

2

Anticipated Usual
Use Level (ppm)

AnticipatedMaximum Use
Level (ppm)

FEMA No.

Primary Name

2772

NEROLIDOL (ISOMER UNSPECIFIED)

1

100

2773

NERYL ACETATE

35

500

2774

NERYL BUTYRATE

510NERYL ISOBUTYRATE

5

10
30

2

5

2775

METHYL ACETATE

2

100

2776

NERYL FORMATE

15

O-METHYLANISOLE

45

55

2778

NERYL ISOVALERATE

41

45

2688

ALPHA-METHYLBENZYL FORMATE

2

5

2780

2,6-NONADIEN-1-OL

5

20

2690

METHYL P-TERTBUTYLPHENYLACETATE

10

25

2783

1,3-NONANEDIOL ACETATE(MIXED ESTERS)

1

5
20

2675

2-METHOXY-4-VINYLPHENOL

2676
2680

2692

3-METHYLBUTYRALDEHYDE

760

5,000

2785

2-NONANONE

16

2695

2-METHYLBUTYRIC ACID

100

2,000

2791

NONYL ISOVALERATE

1

2

2698

METHYL CINNAMATE

100

780

2792

NUTMEG (MYRISTICA FRAGRANSHOUTT. (MYRISTICACEAE))

20

20

2794

OAK CHIPS EXTRACT (QUERCUS
ALBA L. (FAGACEAE))

115

200

2795

OAK MOSS, ABSOLUTE – EVERNIAPRUNASTRI (L.) ACH., E. FURFURACEA(L.) MANN, AND OTHER LICHENS

1

1

2699

6-METHYLCOUMARIN

100

300

2700

METHYLCYCLOPENTENOLONE

690

3,560

2701

4-(3,4-METHYLENEDIOXYPHENYL)2-BUTANONE

70

480

2702

5-METHYLFURFURAL

20

500

2703

METHYL 2-FUROATE

25

155

2801

2-OCTANOL

10100

3-OCTANONE

5

10
300

2704

2-METHYL-3(2-FURYL)ACROLEIN

15

500

2803

2706

2-METHYLHEPTANOIC ACID

12

100

2808

OCTYL ISOBUTYRATE

150

1,000

2810

OCTYL HEPTANOATE

1

3

OLEIC ACID

1

100

2708

METHYL HEXANOATE

105

2717

METHYL O-METHOXYBENZOATE

1

10

2815

2725

METHYL 2-NONENOATE

25

1,000

2816

6

30

2726

METHYL 2-NONYNOATE

375

1,000

OLIBANUM, OIL [BOSWELLIACARTERI BIRDW. AND OTHER
BOSWELLIA SPP.]-FRANKINCENSE

2727

2-METHYLOCTANAL

150

300

2819

50

135

2728

METHYL OCTANOATE

0.1

0.2

ORANGE FLOWERS (CITRUS
AURANTIUM L. (RUTACEAE))

2731

4-METHYL-2-PENTANONE

5

10

2831

PALMAROSA, OIL – CYMBOPOGONMARTINI (ROXB.) STAPF

8

11

2734

3-METHYL-4-PHENYL3-BUTENE-2-ONE

900

6,650

2832

PALMITIC ACID

1

1

2735

2-METHYL-4-PHENYL2-BUTYL ACETATE

500

1,000

2833

PAPRIKA (CAPSICUM ANNUUM
L. (SOLANACEAE))

50

500

2740

4-METHYL-1-PHENYL-2-PENTANONE

475

1,300

2834

PAPRIKA OLEORESIN (CAPSICUM
ANNUUM L. (SOLANACEAE))

2

800

2741

METHYL 3-PHENYLPROPIONATE

50

250

2835

100

3-(METHYLTHIO)PROPIONALDEHYDE

1

5PARSLEY – PETROSELINUMCRISPUM (MILLER) NYMAN(P. SATIVUM HOFFM.)

2

2747
2750

METHYL 9-UNDECENOATE

1,800

5,500

2840

OMEGA-PENTADECALACTONE

1

5

2751

METHYL 2-UNDECYNOATE

5

10

2842

2-PENTANONE

15

15

2752

METHYL VALERATE

250

500

2843

4-PENTENOIC ACID

9

27

2754

2-METHYLVALERIC ACID

2

500

2845

1

50

2755

MIMOSA ABSOLUTE (ACACIA
DECURRENS WILLD. VAR.
DEALBATA (LEGUMINOSAE))

1

3

PEPPER, BLACK, OIL (PIPERNIGRUM L.(PIPERACEAE))

2846

PEPPER, BLACK, OLEORESIN (PIPERNIGRUM L.(PIPERACEAE))

50

410

2757

MOUNTAIN MAPLE EXTRACT SOLID(ACER SPICATUM LAM. (ACERACEAE))

100

165

2853

PETITGRAIN, LEMON, OIL (CITRUS
LIMON L. BURM. F (RUTACEAE))

20

30

2759

MUSK TONQUIN (MOSCHUS
MOSCHIFERUS L. (MOSCHIDAE))

60

230

2854

PETITGRAIN MANDARIN OIL(CITRUS RETICULATA BLANCO
VAR. MANDARIN (RUTACEAE))

1

1

2857

PHENETHYL ACETATE

10

30

2859

PHENYLETHYL ANTHRANILATE

5

10

2860

PHENETHYL BENZOATE

45

90

2763

MYRISTALDEHYDE

0.5

1

2764

MYRISTIC ACID

6

10

2769

NARINGEN EXTRACT (CITRUS
PARADISI MACF. (RUTACEAE))

2

10

07.11 • www.ift.org

71 pg

GRAS FLAVORING SUBSTANCES 25

Table 4 continued- Updated Average Usual Use Levels/Average Maximum Use Levels in Chewing Gum
Updated average usual use levels (ppm)/average maximum use levels (ppm) in chewing
gum for flavoring substances previously recognized as FEMA GRAS

Anticipated Usual
Use Level (ppm)

AnticipatedMaximum Use
Level (ppm)

PHENETHYL BUTYRATE

40

95

2963

PHENETHYL CINNAMATE

1

5

2964

2870

PHENETHYL TIGLATE

10

10

2965

ISOPULEGYL ACETATE

50

500

2873

2-PHENOXYETHYL ISOBUTYRATE

15

30

2968

PYROLIGNEOUS ACID, EXTRACT

0.005

0.01

2876

PHENYLACETALDEHYDEDIMETHYL ACETAL

1

2

2970

PYRUVIC ACID

10

30

2984

RHODINYL FORMATE

65

500

2990

ROSE HIPS, EXTRACT [ROSA CANINA
L.; R. GALLICA L.; R. CONDITA SCOP.;
R. RUGOSA THUNB.; AND OTHER ROSA
SPP.] – HIPBERRIES, EXTRACT

1

1

2992

ROSEMARY OIL (ROSEMARINUS
OFFICINALIS L. (LAMIACEAE))

1

100

2993

ROSE WATER, STRONGER – ROSACENTIFOLIA L.

1

1

2995

RUE OIL (RUTA GRAVEOLENS
L. (RUTACEAE))

1

1

2998

SAFFRON (CROCUS SATIVUS
L. (IRIDACEAE))

50

55

2999

SAFFRON EXTRACT (CROCUS
SATIVUS L. (IRIDACEAE))

1

1

3000

SAGE (SALVIA OFFICINALIS
L. (LAMIACEAE))

10

350

3001

SAGE OIL (SALVIA OFFICINALIS
L.(LAMIACEAE))

3

350

3002

SAGE OLEORESIN (SALVIA
OFFICINALIS L.(LAMIACEAE))

10

350

3003

SAGE, SPANISH, OIL – SALVIALAVANDULAEFOLIA VAHL.

6

50

3014

SAVORY, SUMMER, OLEORESIN(SATUREJA HORTENSIS L.)

430

990

3015

SAVORY, WINTER (SATUREJAMONTANA L.(LAMIACEAE))

1

30

3016

SAVORY WINTER OIL (SATUREJAMONTANA L.(LAMIACEAE))

1

30

3017

SAVORY, WINTER, OLEORESIN(SATUREJA MONTANA L.(LAMIACEAE))

210FEMA NO.

Primary Name

2861
2863

2878

PHENYLACETIC ACID

10

150

2880

4-PHENYL-3-BUTEN-2-OL

1

2

2881

4-PHENYL-3-BUTEN-2-ONE

15

30

2883

1-PHENYL-3-METHYL-3-PENTANOL

15

100

2886

2-PHENYLPROPIONALDEHYDE

1

5FEMA NO.

Anticipated Usual
Use Level (ppm)

AnticipatedMaximum Use
Level (ppm)

PULEGONE75

350

ISOPULEGONE

20

100

Primary Name

2894

3-PHENYLPROPYL CINNAMATE

20

250

2895

3-PHENYLPROPYL FORMATE

1,060

7,220

2896

3-PHENYLPROPYL HEXANOATE

2,450

2,460

2897

3-PHENYLPROPYL PROPIONATE

1

50

2899

3-PHENYLPROPYL ISOVALERATE

675

5,850

2902

ALPHA-PINENE

175

1,300

2904

PINE NEEDLE, DWARF, OIL [PINUS
MUGO TURRE VAR. PUMILIO(HAENKE) ZENARI]—PINUS PUMILIO,OIL; PINE, MOUNTAIN, OIL

1

1

2905

PINE NEEDLE, OIL [ABIESSIBIRICA LEDEB.; A. ALBA MILL.;
A. SACHALINENSIS MASTERS;
A. MAYRIANA MIYABE AND
KUDO]—SIBERIAN FIR, OIL

100

270

2910

D-PIPERITONE

40

350

2911

PIPERONAL

60

875

2912

PIPERONYL ACETATE

10

25

2913

PIPERONYL ISOBUTYRATE

1

200

2921

POTASSIUM SORBATE

10

20

2922

PROPENYLGUAETHOL

6,070

16,2502923

PROPIONALDEHYDE

250

600

2924

PROPIONIC ACID

100

300

3025

SODIUM BENZOATE

1020SODIUM CITRATE

100

1,000

2926

ISOPROPYL ACETATE

180

310

3026

2928

PROPYL ALCOHOL

160

200

3030

SPEARMINT (MENTHA
SPICATA L.(LAMIACEAE))

6,900

13,5003031

SPEARMINT EXTRACT (MENTHA
SPICATA L.(LAMIACEAE))

525

525

2929

ISOPROPYL ALCOHOL

30

600

2930

P-PROPYLANISOLE

225

393

2931

PROPYL BENZOATE

10

35

3035

STEARIC ACID

20

35

35

3037

STYRAX, EXTRACT – LIQUIDAMBERORIENTALIS MILL.; L. STYRACIFLUA L.

10

150

3043

TARRAGON (ARTEMISIADRACUNCULUS L.(ASTERACEAE))

1

100

2933

P-ISOPROPYLBENZYL ALCOHOL

1

2934

PROPYL BUTYRATE

3

6

2935

ISOPROPYL BUTYRATE

5

50

2937

ISOPROPYL ISOBUTYRATE

5

50

3044

TARTARIC ACID (D-, L-, DL-, MESO-)

500

5,000

2939

ISOPROPYL CINNAMATE

20

30

3055

TETRAHYDROFURFURYL ACETATE

10

15

2943

PROPYL FORMATE

1

2

3056

TETRAHYDROFURFURYL ALCOHOL

5

10

2949

PROPYL HEXANOATE

15

25

3058

TETRAHYDROFURFURYL PROPIONATE

5

10

2

3059

3,4,5,6-TETRAHYDROPSEUDOIONONE

5

10

3065

THYME, WHITE, OIL (THYMUS
VULGARIS L.(LAMIACEAE))

1

50

2960

PROPYL ISOVALERATE

1

2961

ISOPROPYL ISOVALERATE

35

35

2962

ISOPULEGOL

1,000

1,000

pg 72

07.11 • www.ift.org

FEMA NO.

Primary Name

Anticipated Usual
Use Level (ppm)

AnticipatedMaximum Use
Level (ppm)

FEMA NO.

Primary Name

Anticipated Usual
Use Level (ppm)

AnticipatedMaximum Use
Level (ppm)

3066

THYMOL

5

2,500

3194

2-METHYL-2-PENTENAL

1

100

3083

TRIETHYL CITRATE

225

950

3195

2-METHYL-2-PENTENOIC ACID

2,500

10,0003092

UNDECANAL

1

4

3196

3-METHYL-2-(2-PENTENYL)2-CYCLOPENTEN-1-ONE

200

500

3199

5-METHYL-2-PHENYL-2-HEXENAL

1

5

3200

4-METHYL-2-PHENYL-2-PENTENAL

1,300

2,575

3093

2-UNDECANONE

20

35

3095

10-UNDECENAL

1,000

2,500

3097

UNDECYL ALCOHOL

100

1,000

3099

VALERIAN ROOT EXTRACT (VALERIANA
OFFICINALIS L. (VALERIANACEAE))

2

250

3201

METHYL PROPYL DISULFIDE

100

300

3202

METHYL 2-PYRROLYL KETONE

1

1

4-METHYL-5-THIAZOLEETHANOL

1

2

3103

GAMMA-VALEROLACTONE

1

5

3204

3106

VANILLA, OLEORESIN – VANILLA
PLANIFOLIA ANDREWS OR V.
TAHITENSIS J.W. MOORE

170

225

3208

(METHYLTHIO)METHYLPYRAZINE(MIXTURE OF ISOMERS)

10

15

3109

VERATRALDEHYDE

30

30

3209

5-METHYL-2THIOPHENECARBOXALDEHYDE

50

100

3111

WALNUT HULL, EXTRACT – JUGLANSNIGRA L. OR J. REGIA L.

50

240

3212

2,4-NONADIENAL

3124

ZINGERONE

170

500

3213

2-NONENAL

3135

2-TRANS,4-TRANS-DECADIENAL

5

10

3136

2,3-DIETHYLPYRAZINE

100

185

3142

3,7-DIMETHYL-6-OCTENOIC ACID

710

2,200

3144

P,ALPHA-DIMETHYLSTYRENE

160

485

3148

ETHYL TRANS-2,CIS-4-DECADIENOATE

20

1,000

3151

2-ETHYL-1-HEXANOL

750

4,400

3152

3-ETHYL-2-HYDROXY-2CYCLOPENTEN-1-ONE

2,700

7,500

5

10

1,000

5,000

3214

DELTA-OCTALACTONE

10

500

3215

2-OCTENAL

500

5,000

3217

2,4-PENTADIENAL

415

1,200

3218

2-PENTENAL

10

15

3223

PHENOL

1

10

3224

2-PHENYL-2-BUTENAL

1

4

3226

1-PHENYL-1,2-PROPANEDIONE

1

5

3235

4,5,6,7-TETRAHYDRO-3,6DIMETHYLBENZOFURAN

200

1,000

3236

TETRAHYDRO-4-METHYL-2-(2METHYLPROPEN-1-YL)PYRAN

5

10
1

3154

2-ETHYL-5-METHYLPYRAZINE

30

65

3159

FURFURYL METHYL ETHER

1

5

3161

FURFURYL ISOPROPYL SULFIDE

40

75

3237

2,3,5,6-TETRAMETHYLPYRAZINE

1

3162

FURFURYL THIOACETATE

10

50

3238

2,2’-(THIODIMETHYLENE)-DIFURAN

154-THUJANOL

20

1,000

3163

2-FURYL METHYL KETONE

4,770

3239

3165

TRANS-2-HEPTENAL

5

10

3242

1,300

NOOTKATONE

15

50

P-ALPHA,ALPHATRIMETHYLBENZYL ALCOHOL

190

3166
3169

TRANS-2-HEXENOIC ACID

35

100

3243

1-(2,6,6-TRIMETHYL-1CYCLOHEXEN-1-YL)-2-BUTEN-1-ONE

10

100

3170

3-HEXENOIC ACID

1.5

3

3244

2,3,5-TRIMETHYLPYRAZINE

1

5

3171

CIS-3-HEXEN-1-YL ACETATE100

10,0003247

10-UNDECENOIC ACID

1.5

3

3173

1-HYDROXY-2-BUTANONE

100

600

3249

2,6-XYLENOL

2

5

3174

4-HYDROXY-2,5-DIMETHYL3(2H)-FURANONE

100

1,000

3251

2-ACETYLPYRIDINE

1

1

3175

GAMMA-IONONE

1

5

3268

3,4-DIMETHYL-1,2CYCLOPENTADIONE

15

30

3269

3,5-DIMETHYL-1,2CYCLOPENTADIONE

10

15

3271

2,3-DIMETHYLPYRAZINE

1

1

3275

DIMETHYL TRISULFIDE

2

5

3286

GLYCERYL TRIPROPANOATE

1

5

3289

4-HEPTENAL

0.1

1

3291

4-HYDROXYBUTANOIC ACID LACTONE

60

270

3293

4-HYDROXY-3-PENTENOICACID LACTONE

1

5

3294

5-HYDROXYUNDECANOICACID LACTONE

25

500

3303

2-METHYL-1-BUTANETHIOL

3

5

1,600

3176

P-MENTHAN-2-ONE

5,000

9,800

3177

P-MENTHA-8-THIOL-3-ONE

1

5

3180

2-MERCAPTOPROPIONIC ACID

1

5

3181

O-METHOXYCINNAMALDEHYDE

5

50

3183

2,5 OR 6-METHOXY3-METHYLPYRAZINE(MIXTURE OF ISOMERS)

1

1

3189

2-METHYL-3-,5 OR
6-(FURFURYLTHIO)PYRAZINE(MIXTURE OF ISOMERS)

5

10

3190

5-METHYL-2,3-HEXANEDIONE

5

10

3191

2-METHYLHEXANOIC ACID

500

5,000

07.11 • www.ift.org

73 pg

GRAS FLAVORING SUBSTANCES 25

Table 4 continued- Updated Average Usual Use Levels/Average Maximum Use Levels in Chewing Gum
Updated average usual use levels (ppm)/average maximum use levels (ppm) in chewing
gum for flavoring substances previously recognized as FEMA GRAS

Anticipated Usual
Use Level (ppm)

AnticipatedMaximum Use
Level (ppm)

FEMA NO.

Primary Name

3305

1-METHYL-2,3-CYCLOHEXADIONE

5

15

3306

5H-5-METHYL-6,7DIHYDROCYCLOPENTA(B)PYRAZINE

80

100

3309

2-METHYLPYRAZINE

30

65

3310

METHYL THIOBUTYRATE

10

20

3311

METHYL 2-THIOFUROATE

10

50

3312

3-METHYLTHIOPROPYLISOTHIOCYANATE

160

860

Anticipated Usual
Use Level (ppm)

AnticipatedMaximum Use
Level (ppm)

1-(2,6,6-TRIMETHYLCYCLOHEXA1,3-DIENYL)-2-BUTEN-1-ONE

100

300

3421

2,6,6-TRIMETHYLCYCLOHEX2-ENE-1,4-DIONE

1

5

3422

2,4-UNDECADIENAL

15

15

3424

3-ACETYLPYRIDINE

1

1

3427

2,4-DIMETHYLBENZALDEHYDE

1

2

3428

ETHYL 3-HYDROXYBUTYRATE

350

4,000

3433

2-METHOXY-3-(1METHYLPROPYL)PYRAZINE

1

2
75

FEMA NO.

Primary Name

3420

3316

2-PENTANOL

1,500

2,000

3317

2-PENTYLFURAN

1

5

3322

THIAMINE HYDROCHLORIDE

5

15

3435

1-METHYL-1-CYCLOPENTEN-3-ONE

75

3324

3,5,5-TRIMETHYL-1-HEXANOL

1

100

3438

3-(METHYLTHIO)-1-HEXANOL

1

5

3327

2-ACETYL-3,5(AND6)-DIMETHYLPYRAZINE

1

1

3442

2,6,10-TRIMETHYL-2,6,10PENTADECATRIEN-14-ONE

5

50

3328

2-ACETYLTHIAZOLE

1

1

3443

VALENCENE

20

1,000

40

3448

DICYCLOHEXYL DISULFIDE

1

5

3450

2,5-DIMETHYL-2,5DIHYDROXY-1,4-DITHIANE

5

10

3454

5-ETHYL-2-HYDROXY-3METHYLCYCLOPENT-2-EN-1-ONE

50

100

3331

BISABOLENE

3336

2,3-DIETHYL-5-METHYLPYRAZINE

10

15

3343

ETHYL 3-METHYLTHIOPROPIONATE

35

200

3347

FURFURYL THIOPROPIONATE

10

50

40

3353

CIS-3-HEXENYL FORMATE

3,500

7,000

3457

HEXYL PHENYLACETATE

3

3

3356

HYDROXYNONANOIC ACID,DELTA-LACTONE

75

200

3459

2-HYDROXY-3,5,5-TRIMETHYL2-CYCLOHEXENONE

3

5

3357

2-KETO-4-BUTANETHIOL

10

10

3461

2-ISOPROPYLPHENOL

1

1

3359

2-METHYLBUTYL 2-METHYLBUTYRATE

15

2,000

3463

4-METHYLPENTANOIC ACID

20

100

3369

2-METHYLPROPYL
3-METHYLBUTYRATE

15

1,000

3465

CIS-6-NONEN-1-OL

0.6

2

3466

2-TRANS-6-TRANS-OCTADIENAL

5

10

3467

CIS-3-OCTEN-1-OL

10

500

3471

1,5,5,9-TETRAMETHYL-13OXATRICYCLO(8.3.0.0(4,9))
TRIDECANE

1

5

3472

THIOGERANIOL

1

5

3486

ETHYL TRANS-2-BUTENOATE

2,800

4,200

3376

4-(METHYLTHIO)-4METHYL-2-PENTANONE

1

5

3377

NONA-2-TRANS-6-CIS-DIENAL

5

50

3378

2,6-NONADIENAL DIETHYL ACETAL

0.1

0.5

3380

9,12-OCTADECADIENOIC ACID (48%)
AND 9,12,15-OCTADECATRIENOICACID (52%)

1

100

3382

1-PENTEN-3-ONE

5

10

3489

ETHYL 2-METHYL-4-PENTENOATE

200

520

3389

2,6,6-TRIMETHYLCYCLOHEXA1,3-DIENYL METHANAL

5

5

3498

3-HEXENYL 3-METHYLBUTANOATE

650

5,000

3390

1,3,3-TRIMETHYL-2NORBORNANYL ACETATE

80

500

3506

2-METHYLBUTYL
3-METHYLBUTANOATE

2

2,000

3393

N-BUTYL 2-METHYLBUTYRATE

1

50

3527

3-ACETYL-2,5-DIMETHYLTHIOPHENE

1

1

1

3536

DIMETHYL DISULFIDE

1

5

3538

2,6-DIMETHYL-3-((2-METHYL3-FURYL)THIO)-4-HEPTANONE

3

5

3539

3,7-DIMETHYL-1,3,6-OCTATRIENE

5

35

3554

5-ISOPROPYL-2-METHYLPYRAZINE

10

15

3557

P-MENTHA-1,8-DIEN-7-AL

5

100

3394
3397

3-ETHYLPYRIDINE

1

ALPHA-FURFURYL PENTANOATE

30

40

3402

CIS-3-HEXENYL BUTYRATE

32

2,000

3403

CIS-3-HEXENYL HEXANOATE

1

100

3406

2-ISOPROPYL-5-METHYL-2-HEXENAL

550

1,700

3408

METHYL DIHYDROJASMONATE

35

180

3410

METHYL JASMONATE

1

50

3411

METHYL LINOLEATE (48%)/METHYL
LINOLENATE (52%) MIXTURE

1

10

3415

3-(METHYLTHIO)PROPANOL

1

5

3417

3-PENTEN-2-ONE

5

10

pg 74

07.11 • www.ift.org

3558

P-MENTHA-1,3-DIENE

25

115

3565

P-MENTH-8-EN-2-ONE

1,200

3,800

3577

3-METHYL-5-PROPYL-2CYCLOHEXEN-1-ONE

5

10

3578

2-METHYL-4-PROPYL1,3-OXATHIANE

5

10

3579

1,4-NONANEDIOL DIACETATE

1

5

FEMA NO.

Primary Name

Anticipated Usual
Use Level (ppm)

AnticipatedMaximum Use
Level (ppm)3584

1-PENTEN-3-OL

5

10

3590

DELTA-TETRADECALACTONE

2

5

3592

(2,2,3-TRIMETHYLCYCLOPENT3-EN-1-YL)ACETALDEHYDE

40

50

3595

2,5-XYLENOL

11

25

3596

3,4-XYLENOL

1

1

3609

2-ACETYL-5-METHYLFURAN

930

3,900

3622

DELTA-1-(2,6,6-TRIMETHYL-3CYCLOHEXEN-1-YL)-2-BUTEN-1-ONE

60

120

3625

BETA-IONOL

40

40

3634

4,5-DIMETHYL-3-HYDROXY2,5-DIHYDROFURAN-2-ONE

1

5

3641

ETHYL TRANS-2-DECENOATE

450

1,000

3643

ETHYL TRANS-2-OCTENOATE

1,500

10,0003657

CAMPHOLENE ACETATE

50

160

3658

1,4-CINEOLE

15

500

3661

NEROL OXIDE

5

10

3665

2,2-DIMETHYL-5-(1METHYLPROPEN-1-YL)
TETRAHYDROFURAN

20

70

3670

TRANS,TRANS-2,4-DODECADIENAL

5

10

3675

ETHYL TRANS-2-HEXENOATE

20

60

3680

2-ETHYL-4-METHYLTHIAZOLE

1

5

3689

CIS-3-HEXENYL CIS-3-HEXENOATE

10

100

3690

CIS-3-HEXENYL LACTATE

20

400

3692

HEXYL TRANS-2-HEXENOATE

0.1

0.1

3695

HYDROQUINONE MONOETHYL ETHER

90

200

3702

METHYLBENZYL ACETATE(MIXED O,M,P)

1

1

3710

METHYL 3-NONENOATE

11,20020,1003746

LINALOOL OXIDE

20

100

3750

OSMANTHUS ABSOLUTE (OSMANTHUS
FRAGRANS LOUR.(OLEACEAE))

2

10

3784

3-L-MENTHOXYPROPANE-1,2-DIOL

300

4,000

3787

2-METHYL-3TETRAHYDROFURANTHIOL

1,480

5,900

3821

DELTA-3-CARENE

55

155

3869

3-METHYL-2-OXOBUTANOIC ACID500

11,4004049

4-HYDROXY-3,5-DIMETHOXYBENZALDEHYDE

15

75

25
07.11 • www.ift.org

75 pg