[Federal Register Volume 60, Number 238 (Tuesday, December 12, 1995)]
[Rules and Regulations]
[Pages 63619-63621]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-30125]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 184

[Docket No. 88G-0318]


Glyceryl Palmitostearate; Affirmation of GRAS Status of Direct 
Food Substance

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending its 
regulations to affirm that glyceryl palmitostearate is generally 
recognized as safe (GRAS) for use as a formulation aid in excipient 
mixtures used in tablets. This action is in response to a petition 
filed on behalf of Gattefosse, S.A.

EFFECTIVE DATE: December 12, 1995.

FOR FURTHER INFORMATION CONTACT: Dennis M. Keefe, Center for Food 
Safety and Applied Nutrition (HFS-206), Food and Drug Administration, 
200 C St. SW., Washington, DC 20204, 202-418-3090.

SUPPLEMENTARY INFORMATION:

 I. Background

 A. Regulatory History

    In accordance with the procedures described in 21 CFR 170.35, a 
petition was submitted (GRASP 8G0344) on behalf of Gattefosse, S.A., 36 
Chemin de Genas, Saint Priest, France, requesting that glyceryl 
palmitostearate be affirmed as GRAS for use as an excipient in tablets.
    FDA published a notice of filing of this petition in the Federal 
Register of October 20, 1988 (53 FR 41241), and gave interested parties 
an opportunity to submit comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, rm.1-23, 12420 Parklawn Dr., 
Rockville, MD 20857. FDA received no comments in response to that 
notice.

B. Standards for GRAS Affirmation

    Under Sec. 170.30 (21 CFR 170.30), general recognition of safety 
may be based only on the views of experts qualified by scientific 
training and 

[[Page 63620]]
experience to evaluate the safety of food substances. The basis of such 
views may be either scientific procedures, or in the case of a 
substance used in food before January 1, 1958, through experience based 
on common use in food. General recognition of safety based upon 
scientific procedures shall require the same quantity and quality of 
scientific evidence as is required to obtain approval of a food 
additive regulation, and ordinarily is to be based upon published 
studies, which may be corroborated by unpublished studies and other 
data and information (Sec. 170.30(b)).
    The subject petition relies on scientific procedures evidence to 
support GRAS affirmation of glyceryl palmitostearate as an excipient in 
tablets.

C. Manufacturing Process and Identity

    -According to information contained in the petition, glyceryl 
palmitostearate is manufactured by heating a mixture of glycerin 
(glycerol) and a mixture of fatty acids of vegetable origin composed of 
roughly equal amounts (48 to 50 percent) of palmitic and stearic acid, 
and 4 percent myristic acid.
    -Glyceryl palmitostearate prepared in this way is a mixture of 
mono-, di-, and triglycerides of palmitic and stearic acids. It 
contains primarily di- and triglycerides (>78.5 percent), a small 
amount of monoglycerides (8 to 17 percent), and trace amounts of free 
glycerin (<1.0 percent) and free palmitic and stearic acid moieties 
(<3.0 percent).-

D. Use and Exposure

    -The proposed use of the substance is as a lubricating agent in 
excipient mixtures for preparation of tablets (vitamin and related 
products). The technical properties of the substance in excipient 
formulations are similar to those of other fatty acid glycerides. The 
petitioner asserts that the normal use level of the substance will be 6 
to 40 percent of the total tablet weight and that the 40 percent level 
is typical for long-duration timed-release formulations. The petitioner 
also estimates that although the typical dosage is approximately two 
tablets per day, some individuals may take as many as six tablets per 
day.
    -Based on a typical dose of two 600-milligram (mg) tablets per 
person per day, FDA estimates that the typical intake of glyceryl 
palmitostearate would be from 72 to 480 mg per person per day (Ref. 2). 
The petitioner estimates that on the basis of 2,000 to 2,700 calories 
per person per day total food intake and 35 percent fat in the diet 
(one-third of all ingested fat being fully saturated), the intake of 
saturated fat per person per day is between 20 and 30 grams. This 
estimate is consistent with dietary data compiled by the United States 
Department of Agriculture (1985). Based on this information, FDA 
concludes that the proposed use of glyceryl palmitostearate will 
increase the dietary intake of saturated fat by 2.4 percent per person 
per day (Ref. 2).

II. Safety

    -The notice of filing in this proceeding used the name ``glyceryl 
palmitostearate'' to represent the substance that is the subject of the 
petition. The agency considers this name to be appropriate, although 
the substance is actually not a single chemical entity, but rather a 
mixture of di- and triglycerides with a small amount of monoglycerides.
    Triglycerides (triacylglycerols) are the most abundant form of fat 
in the human diet (Ref. 1). Their component fatty acids are the major 
energy reserve of plant and animal cells (Ref. 1). When ingested, 
triglycerides are initially digested into free fatty acids and 
diglycerides. Diglycerides are further digested into a mixture of 
monoglycerides, glycerol, and free fatty acids. Monoglycerides, 
glycerol, and free fatty acids are the chemical forms in which dietary 
fats are absorbed into the body (Ref. 1). Thus, all of the components 
of glyceryl palmitostearate are present as components of fats found in 
foods or are generated in large amounts in the human digestive tract 
during the digestion of fat (Ref. 1). As previously stated, the 
proposed use of glyceryl palmitostearate will not result in a material 
increase in exposure to these substances (Ref. 2).
    -The agency has previously examined the safety of the components of 
glyceryl palmitostearate. Glycerin is listed as a multipurpose GRAS 
substance in 21 CFR 182.1320. Mono- and diglycerides prepared from 
fats, oils, or fat-forming acids derived from edible sources, including 
palmitic and stearic acids, are affirmed as GRAS in 21 CFR 184.1505. 
Stearic and palmitic acid are approved as multipurpose food additives 
in 21 CFR 172.860. Glyceryl tristearate, a component of glyceryl 
palmitostearate, is approved as a multipurpose food additive in 21 CFR 
172.811. Glyceryl monostearate is affirmed as GRAS (21 CFR 184.1324).
    -The Select Committee on GRAS Substances (SCOGS) reviewed all 
available toxicological studies on mono- and diglycerides and 
concluded:
    -There is no evidence in the available information on mono- and 
diglycerides of fat-forming fatty acids that demonstrates or 
suggests reasonable grounds to suspect a hazard to the public when 
they are used at levels that are now current or that might 
reasonably be expected in the future.
 (Ref. 4, p. 23.)
    -The Joint Expert Committee on Food Additives (JECFA) of the Food 
and Agriculture Organization and the World Health Organization (FAO/
WHO) has also reviewed the safety of mono- and diglycerides. Based on 
its review, JECFA has concluded that no limit on the acceptable daily 
intake of mono- and diglycerides need be established (Ref. 5).

III. Conclusion

    -FDA concludes that there is no meaningful difference between the 
components of glyceryl palmitostearate and dietary fats or the products 
of digestion of fats. The agency further concludes that there will not 
be a materially significant increase in exposure to these substances 
from the petitioned use of glyceryl palmitostearate. The safety of the 
mono- and diglyceride components of glyceryl palmitostearate has been 
reviewed by independent bodies of experts qualified by training and 
experience to evaluate the safety of food ingredients. These experts 
have concluded that mono- and diglycerides are safe. The information 
that the agency used to arrive at these conclusions is publicly 
available in published form (Refs. 1, 3, 4, and 5).
    -FDA, therefore, concludes that the petitioned use of glyceryl 
palmitostearate fully meets the requirements outlined in Sec. 170.30(b) 
for GRAS affirmation based on scientific procedures. Therefore, in 
accordance with 21 CFR 184.1(b)(1), the agency is affirming that the 
use of glyceryl palmitostearate as a formulation aid in excipients for 
tablets is GRAS with no limitations other than current good 
manufacturing practice. The agency is listing the specific use as a 
formulation aid in excipients for tablets in the regulation solely to 
reflect that the affirmation of GRAS status is based on the evaluation 
of this use.

IV. Environmental Impact

    -The agency has determined under 21 CFR 25.24(b)(7) that this 
action is of a type that does not individually or cumulatively have a 
significant effect on the human environment. Therefore, neither an 
environmental assessment nor an environmental impact statement is 
required.

V. Economic Impact

    -FDA has examined the impacts of this final rule under Executive 
Order 12866 and the Regulatory Flexibility Act (Pub. 

[[Page 63621]]
L. 96-354). Executive Order 12866 directs agencies to assess all costs 
and benefits of available regulatory alternatives and, when regulation 
is necessary, to select regulatory approaches that maximize net 
benefits (including potential economic, environmental, public health 
and safety, and other advantages; distributive impacts; and equity). 
The agency believes that this final rule is consistent with the 
regulatory philosophy and principles identified in Executive Order 
12866. In addition, the final rule is not a significant regulatory 
action as defined by the Executive Order and so is not subject to 
review under the Executive Order.
    -The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact on small 
entities. Because no current activity is prohibited by this final rule, 
the compliance cost to firms is zero. Because no increase in the health 
risks faced by consumers will result from this final rule, total costs 
are also zero. Potential benefits include wider use of this substance 
because of reduced uncertainty concerning its GRAS status, and any 
resources saved by eliminating the need to prepare further petitions to 
affirm the GRAS status of this substance for this use. The agency 
certifies, therefore, that the final rule will not have a significant 
economic impact on a substantial number of small entities. Therefore, 
under the Regulatory Flexibility Act, no further analysis is required.

VI. References

    The following references have been placed on display in the Dockets 
Management (address above) and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday.-
    -1. Gurr, M. I., and A. T. James, Lipid Biochemistry: An 
Introduction, John Wiley and Sons, Inc., New York, 1975.
    -2. Memorandum dated September 6, 1988, from M. Dinovi to J. 
Ziyad, ``GRP 8G0344--Parexel Int. Corp. (PI) for Gattefosse, SA. 
Glyceryl Palmitostearate.''
    -3. Park, Y. K., and E. A. Yetley ``Trend Changes in Use and 
Current Intakes of Tropical Oils in The United States'' American 
Journal of Clinical Nutrition 51:738-748, 1990.
    -4. Select Committee on GRAS Substances. ``Evaluation of the 
Health Aspects of Glycerin and Glycerides as Food Ingredients'' 
(SCOGS-30) PB-254 536, 1975.
    -5. Food and Agriculture Organization of the United Nations, 
``Toxicological Evaluation of Some Food Additives Including 
Anticaking Agents, Antimicrobials, Antioxidants, Emulsifiers and 
Thickening Agents.'' FAO Nutrition Meetings Report Series No. 53A, 
Rome, 1974.

-List of Subjects in 21 CFR Part 184

    -Food additives, Food ingredients.
    -Therefore, under the Federal Food, Drug, and Cosmetic Act and 
under authority delegated to the Commissioner of Food and Drugs and 
redelegated to the Director, Center for Food Safety and Applied 
Nutrition, 21 CFR part 184 is amended as follows:

-PART 184--DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED 
AS SAFE

    -1. The authority citation for 21 CFR part 184 continues to read as 
follows:

    -Authority: Secs. 201, 402, 409, 701 of the Federal Food, Drug, 
and Cosmetic Act (21 U.S.C. 321, 342, 348, 371).

    -2. New Sec. 184.1329 is added to subpart B to read as follows:


Sec. 184.1329   Glyceryl palmitostearate.

    -(a) Glyceryl palmitostearate is a mixture of mono-, di-, and 
triglyceryl esters of palmitic and stearic acids made from glycerin, 
palmitic acid, and stearic acid.
    -(b) The ingredient meets the following specifications:
    -(1) The substance is a mixture of
mono-, di-, and triglycerides of palmitic acid and stearic acid.
    -(2) Heavy metals (as lead): Not more than 10 parts per million.
    -(c) In accordance with Sec. 184.1(b)(1), the ingredient is used in 
food with no limitation other than current good manufacturing practice. 
The affirmation of this ingredient as generally recognized as safe 
(GRAS) as a direct human food ingredient is based upon the following 
current good manufacturing practice conditions of use:
    -(1) The ingredient is used as a formulation aid, as defined in 
Sec.  170.3(o)(14) of this chapter.
    -(2) The ingredient is used in excipient formulations for use in 
tablets at levels not to exceed good manufacturing practice.

    Dated: November 16, 1995.
Janice F. Oliver,
Deputy Director for Systems and Support, Center for Food Safety and 
Applied Nutrition.
[FR Doc. 95-30125 Filed 12-11-95; 8:45 am]
BILLING CODE 4160-01-F