[Federal Register Volume 63, Number 85 (Monday, May 4, 1998)]
[Rules and Regulations]
[Pages 24416-24419]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-11681]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 184

[Docket No. 90G-0412]


Lipase Enzyme Preparation From Rhizopus Niveus; Affirmation of 
GRAS Status as a Direct Food Ingredient

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 lipase enzyme preparation derived from 
Rhizopus niveus is generally recognized as safe (GRAS) for use as a 
direct human food ingredient. This action is in response to a petition 
submitted by Fuji Oil Co., Ltd.

DATES: The regulation is effective May 4, 1998. The Director of the 
Office of the Federal Register approves the incorporation by reference 
in accordance with 5 U.S.C. 552(a) and 1 CFR part 51 of a certain 
publication listed in Sec. 184.1420 (21 CFR 184.1420), effective May 4, 
1998.

FOR FURTHER INFORMATION CONTACT:  Linda S. Kahl, Center for Food Safety 
and Applied Nutrition (HFS-206), Food and Drug Administration, 200 C 
St. SW., Washington, DC 20204, 202-418-3101.

SUPPLEMENTARY INFORMATION: 

I. Background

    In accordance with the procedures described in 21 CFR 170.35, Fuji 
Oil Co., Ltd., submitted a petition (GRASP 7G0330) requesting that 
lipase-protease enzyme preparation from R. niveus be affirmed as GRAS 
for use as a direct human food ingredient. FDA published a notice of 
filing of this petition in the Federal Register of June 18, 1992 (57 FR 
27256), and gave interested persons an opportunity to submit comments 
to the Dockets Management Branch (HFA-305), Food and Drug 
Administration, 12420 Parklawn Dr., rm. 1-23, Rockville, MD 20857. FDA 
received no comments in response to the filing notice.
    Although the petitioner proposed that the subject enzyme 
preparation be called by the common or usual name ``lipase-protease,'' 
the proposed use of the enzyme preparation is solely for its lipase 
activity. The GRAS exemption described in section 201(s) of the Federal 
Food, Drug, and Cosmetic Act (21 U.S.C. 321(s)) specifies that a GRAS 
substance must be generally recognized as safe ``under the conditions 
of its intended use.'' Thus, affirmation of GRAS status pertains to the 
particular use of a substance. Accordingly, FDA considers the enzyme 
preparation that is the subject of this document to be ``lipase enzyme 
preparation.'' To avoid confusion between lipase, the enzyme, and the 
lipase-containing enzyme preparation, which contains lipase as its 
characterizing enzyme activity, but which also contains diatomaceous 
earth as a carrier and may contain other enzyme activities and 
impurities, this document will henceforth use the terms ``lipase'' to 
refer to the enzyme and ``lipase enzyme preparation'' to refer to the 
fermentation-derived lipase enzyme preparation, including the carrier 
diatomaceous earth.

II. 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 experience to evaluate the safety of substances directly 
or indirectly added to food. The basis of such views may be either 
scientific procedures or, in the case of a substance used in food prior 
to January 1, 1958, experience based on common use in food. General 
recognition of safety based upon scientific procedures requires the 
same quantity and quality of scientific evidence as is required to 
obtain approval of a food additive regulation and ordinarily is based 
upon published studies, which may be corroborated by unpublished 
studies and other data and information (Sec. 170.30(b)). General 
recognition of safety through experience based on common use in food 
prior to January 1, 1958, may be determined without the quantity or 
quality of scientific procedures required for approval of a food 
additive regulation, and ordinarily is based upon generally available 
data and information.
    FDA has evaluated Fuji Oil Co., Ltd.'s petition on the basis of 
scientific procedures to establish that the use of lipase enzyme 
preparation as an enzymatic catalyst for the interesterification of 
fats and oils is GRAS. In evaluating the petition, FDA considered: (1) 
Published and unpublished data and information relating to the identity 
and function of the enzyme component (i.e., lipase) (Refs. 1 through 
5); (2) published and unpublished data and information relating to the 
production organism (Ref. 6); and (3) published and unpublished 
information, methods, and principles relating to the methods and 
processing aids used in the manufacture of the enzyme preparation 
(Refs. 4 and 7 through 10).

III. Safety Evaluation

A. Introduction

    Commercial enzyme preparations that are used in food processing 
typically are not chemically pure but contain, in addition to the 
enzyme component, other components that derive from the production 
organism and the fermentation media, residual amounts of processing 
aids, and substances used as stabilizers, preservatives or diluents. 
Issues relevant to a safety evaluation of the enzyme preparation 
therefore include the safety of the enzyme component, the safety of the 
enzyme source, and the safety of processing aids and other substances 
added during the manufacturing process. As with all substances added to 
food, a safety evaluation of an enzyme preparation also includes 
consideration of dietary exposure to that preparation.

B. The Enzyme Component

    Triglycerides are fats or oils comprised of fatty acids linked by 
ester bonds to each of the three hydroxyl groups of glycerol. 
Triacylglycerol lipases catalyze the hydrolysis of these ester bonds 
and can be grouped according to their specificity. The lipase produced 
by Geotrichum candidium, for example, preferentially cleaves 
triglycerides containing long-chain fatty acids with a cis double bond 
in the 9-position, but such specificity for the hydrolysis of esters 
containing a particular type of fatty acid is unusual. Several other 
lipases (e.g., the lipase derived from Candida cylindracae) are 
nonspecific with respect to either the chemical structure of the fatty 
acid moiety, or the position of the ester bond, that is hydrolyzed; 
these lipases catalyze the complete breakdown of triglycerides into 
glycerol and free fatty acids, and the mono- and diglycerides that are 
intermediates in the reaction do not normally accumulate (Refs. 2 and 
4).
    The largest group of triacylglycerol lipases exhibits specificity 
with respect to the position of the ester bond that is cleaved, i.e., 
only bonds at the 1- or 3-position of the glycerol component are 
hydrolyzed. Most of the lipases that are commonly used in food 
processing (e.g., animal lipase, esterase-lipase from Mucor miehei, and 
lipases derived from Aspergillus niger, M. javanicus, and R. delemar), 
including the R. niveus-derived lipase that is the subject of this 
document, belong to this group (EC No. 3.1.1.3; CAS Reg. No. 9001-62-1) 
(Refs. 2, 4, and 11).
    Although the petitioner did not address the detailed molecular 
structure of lipase from R. niveus, most lipases that have been 
characterized at the

[[Page 24417]]

molecular level are glycoproteins that contain between 2 and 15 percent 
carbohydrates, with mannose as the major glycoside (Ref. 4). Lipases 
from animal and microbial sources have a long history of use in food. 
Animal lipase (21 CFR 184.1415) is affirmed as GRAS based on its common 
use in food prior to January 1, 1958. Esterase-lipase from the fungus 
M. miehei (21 CFR 173.140) is approved for use as a food additive. 
These enzymes are commonly used to enhance flavor production in cheese 
and in butterfat (Refs. 1, 12, and 13). In addition, lipases from 
animal sources (e.g., bovine stomach and hog or porcine pancreas) and 
microbial sources (including R. arrhizus, R. delemar, and R. niveus) 
have been listed in the Codex Alimentarius Commission ``Inventory of 
Processing Aids'' (Ref. 14).
    The reaction product of the R. niveus-derived lipase is a mixture 
of mono- and diglycerides and free fatty acids (Refs. 2 through 5). The 
reaction catalyzed by this lipase is reversible and, therefore, under 
appropriate conditions the enzyme can catalyze the synthesis of 
triglycerides from a mixture of glycerides and free fatty acids. When 
this combination of hydrolysis and synthesis occurs within a mixture of 
triglycerides, or within a mixture of triglycerides and fatty acid 
esters, the reaction products are triglycerides that have been 
interesterified, i.e., triglycerides in which the fatty acid components 
have been exchanged between triglyceride molecules or between 
triglyceride molecules and fatty acid esters (Refs. 1 through 5). For 
example, the GRAS food ingredient ``cocoa butter substitute primarily 
from palm oil'' may be manufactured by the lipase-catalyzed 
interesterification of partially saturated palm oil-derived 
triglycerides with the fatty acid ester ethyl stearate (21 CFR 
184.1259).
    Interesterification also can be achieved through the use of 
chemical catalysts such as sodium methylate. Such chemical catalysis 
results in random interesterification, in which fatty acid interchange 
occurs at all three positions on the glycerol backbone. In contrast, 
enzymatic catalysis with a lipase, such as the lipase that is the 
subject of this document, results in selective interesterification at 
the 1- and 3-positions only. Random interesterification is used 
commercially in the manufacture of margarines and shortenings, but 
lipase-catalyzed selective interesterification, which allows an 
unsaturated fatty acid to remain at the 2-position, is important in the 
manufacture of fats and oils used in confectionery, such as cocoa 
butter substitute primarily from palm oil (Refs. 2 through 4). The 
petitioner stated that one of the primary uses of R. niveus-derived 
lipase enzyme preparation would be in the manufacture of cocoa butter 
substitute primarily from palm oil.
    In general, issues relevant to a safety evaluation of proteins such 
as the enzyme component of an enzyme preparation are potential toxicity 
and allergenicity (Ref. 15). Pariza and Foster (Ref. 15) note that very 
few toxic agents have enzymatic properties, and those that do (e.g., 
diphtheria toxin and certain enzymes in the venom of poisonous snakes) 
catalyze unusual reactions that are not related to the reactions 
catalyzed by enzymes that are commonly used in food processing, such as 
the lipase that is the subject of this document. Further, the agency 
has recently noted, in the context of guidance to industry regarding 
the safety assessment of new plant varieties, that enzymes themselves 
do not generally raise safety concerns (57 FR 22984 at 23005, May 29, 
1992). Exceptions include enzymes that produce substances that are not 
ordinarily digested and metabolized, or that produce toxic substances.
    The catalytic activities of the lipase that is the subject of this 
document are well known. As already discussed, lipase catalyzes two 
related reactions: (1) The splitting of commonly consumed triglycerides 
into smaller components, i.e., fatty acids and mono- and diglycerides; 
and (2) the synthesis of triglycerides from fatty acids and mono- and 
diglycerides. The reaction products (i.e., fatty acids, mono- and 
diglycerides, and triglycerides) from both of these reactions are 
readily metabolized by the human body and do not have toxic properties 
(Ref. 16).
    The agency is not aware of any reports of allergic reactions 
associated with the ingestion of enzymes derived from Rhizopus species. 
There have been, however, some reports of allergies and primary 
irritations from skin contact with enzymes or from inhalation of dust 
from concentrated enzymes (e.g., proteases used in the manufacture of 
laundry detergents) (Refs. 17 through 19). These reports relate 
primarily to workers in production plants (Ref. 18) and are not 
relevant to an evaluation of the safety of ingestion of such enzymes in 
food. Moreover, Pariza and Foster (Ref. 15) note that there are no 
confirmed reports of primary irritations in consumers caused by 
residues of food processing enzymes in food.
    FDA concludes that generally available and accepted data and 
information establish that the use of lipase in food raises no toxicity 
or allergenicity concerns. FDA also concludes that generally available 
and accepted data and information establish that the lipase that is the 
subject of this document is capable of achieving its intended technical 
effect. Finally, FDA concludes that generally available and accepted 
data and information establish that the lipase that is the subject of 
this document is similar in function to other lipases that are used in 
food processing to catalyze the hydrolysis of ester bonds at the 1- or 
3-position of the glycerol component of a triglyceride.

C. Enzyme Source, Manufacturing Methods, and Processing Aids

    The source of the lipase that is the subject of this document is 
the fungus R. niveus. Fungally-derived enzyme preparations used in food 
processing are usually not chemically pure but contain, in addition to 
the enzyme component, other components that derive from the production 
organism and the fermentation media, residual amounts of processing 
aids, and substances used as stabilizers, preservatives or diluents. 
The petitioned enzyme preparation meets the general requirements and 
additional requirements for enzyme preparations in the monograph on 
Enzyme Preparations in the Food Chemicals Codex, 4th ed. (Ref. 20). 
When the R. niveus-derived lipase enzyme preparation is produced in 
accordance with current good manufacturing practice (CGMP), it is 
produced using processing aids that are substances that are acceptable 
for general use in foods and under culture conditions that ensure a 
controlled fermentation, thus preventing the introduction of extraneous 
microorganisms that could be the source of toxic materials and other 
toxic substances (Ref. 20).
    The lipase enzyme preparation is produced in a multistage process 
by controlled fermentation\1\ using a pure culture of the fungus R. 
niveus followed by isolation of the enzyme-containing fraction. Prior 
to its use in the interesterification of fats and oils, the enzyme-
containing fraction is adsorbed onto diatomaceous earth as a carrier. 
These methods are based upon generally available and accepted methods 
used for fermentation, for processing fermentation-derived enzyme-
containing fractions, and for immobilizing an enzyme-containing 
fraction on an insoluble carrier (Refs. 4 and 7 through 10).
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    \1\ The stage of the manufacturing process in which the enzyme 
is being produced by an actively growing culture of microorganisms 
is referred to as fermentation.

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    In the initial stage of the fermentation process, the seed cultures 
of R. niveus are checked for purity and classification after growth on 
a potato-agar medium. The production cultures are suspended in sterile 
water and added to a previously autoclaved wheat bran culture medium. 
After growth for 28 to 32 hours, the broth is checked for quality and 
added to large batch-fermentors containing sterilized growth medium 
(semisolid wheat bran). The culture is monitored until the water 
content and pH value of the resulting malt, which is referred to as the 
``koji,'' reach standard requirements.
    A cell-free extract of the enzymes that are components of the 
fermentation mixture is prepared by sprinkling and steeping the koji 
with cold water, filtering the extracted koji through a filter press 
and a fine filtration apparatus, and precipitating the enzymes that are 
present in the resulting filtrate with ethanol. After decanting the 
supernatant and centrifuging the remaining slurry, the sediment 
containing the extracted enzymes is collected and dried overnight in a 
vacuum-dryer at 40 to 45  deg.C. The dried powder is ground, sized, and 
mixed before storing at room temperature. The finished product is 
adjusted to a standard activity by mixing the enzyme powder with 
dextrin as an excipient. The standardized enzyme powder is adsorbed 
onto diatomaceous earth carrier prior to its use in the 
interesterification of fats or oils. The petitioner provided a 
published scientific review article that discusses this immobilization 
technique with respect to use of lipase enzyme preparations (Ref. 4).
    The production strain of R. niveus that is the source of the lipase 
enzyme is nontoxigenic and nonpathogenic. The manufacturing methods 
completely remove the organism from the enzyme-containing fraction 
(Ref. 4). Moreover, the petitioner provided documentation, based upon 
published methods for strain identification (Ref. 6), showing that the 
production strain was taxonomically identical to the strain used for 
the production of R. niveus-derived amyloglucosidase enzyme 
preparation, which is approved for use as a secondary direct food 
additive (21 CFR 173.110).
    FDA concludes that the presence of added substances and impurities 
that are derived from the enzyme source or that are introduced by 
manufacturing does not present a basis for concern about the safety of 
the lipase enzyme preparation.

D. Dietary Exposure

    FDA considered the estimated dietary exposure to lipase enzyme 
preparation for the proposed use as an enzymatic catalyst in the 
interesterification of fats and oils (Refs. 21 through 23). The 
predominant source of potential exposure to the total organic solids in 
the enzyme preparation will be baked goods that use interesterified fat 
at levels up to 30 percent. The petitioner stated that the standardized 
enzyme powder is adsorbed onto diatomaceous earth carrier prior to its 
use in the interesterification of fats or oils, so that it can be 
removed from the modified triglyceride following the enzyme-catalyzed 
interesterification. Because the adsorbed enzyme preparation is removed 
from the interesterified product following catalysis, no detectable 
enzyme remains in the interesterified product.
    FDA concludes that dietary exposure to the lipase enzyme 
preparation is negligible and therefore does not present a basis for 
concern about use of the lipase enzyme preparation.

IV. Specifications

    The agency finds that, because the potential impurities in the 
lipase enzyme preparation that may originate from the source or 
manufacturing process do not raise any basis for concern about the safe 
use of the preparation, the general requirements and additional 
requirements for enzyme preparations in the monograph on Enzyme 
Preparations in the Food Chemicals Codex, 4th ed. (1996), which are 
being incorporated by reference in accordance with 5 U.S.C. 552(a) and 
1 CFR part 51, are adequate as minimum criteria for food-grade lipase 
enzyme preparation. Lipase assay can be performed using a method 
entitled ``Lipase Activity'' (Ref. 24) or by using any appropriate 
validated method.

V. Conclusions

    The agency has evaluated all available information and finds, based 
upon the published information about the identity and function of 
lipase, that the enzyme component of lipase enzyme preparation will 
achieve its intended technical effect and raises no toxicity or 
allergenicity concerns. In addition, the agency finds, based upon the 
published information about the identity and function of lipase, that 
the enzyme component of the lipase enzyme preparation is similar in 
function to other lipases that are used in food processing to catalyze 
the hydrolysis of ester bonds at the 1- or 3-position of the glycerol 
component of a triglyceride. The agency further finds, based upon 
generally available and accepted information, that when the lipase 
enzyme preparation is manufactured in accordance with Sec. 184.1420, 
the source, R. niveus, and the manufacturing process will not introduce 
impurities into the preparation that may render its use unsafe. 
Finally, the agency finds that dietary exposure to the lipase enzyme 
preparation from the petitioned use does not present a basis for 
concern about use of the lipase enzyme preparation. Therefore, the 
agency concludes, based upon the evaluation of published data and 
information, corroborated by unpublished data and information, and 
based upon scientific procedures (Sec. 170.30(b)), that the lipase 
enzyme preparation described in the regulation set out below is GRAS 
for use as an enzymatic catalyst in the interesterification of fats and 
oils.

VI. Environmental Considerations

    The agency has carefully considered the potential environmental 
effects of this action. FDA has concluded that the action will not have 
a significant impact on the human environment, and that an 
environmental impact statement is not required. The agency's finding of 
no significant impact and the evidence supporting that finding, 
contained in an environmental assessment, may be seen in the Dockets 
Management Branch (address above) between 9 a.m. and 4 p.m., Monday 
through Friday.

VII. Analysis For Executive Order 12866

    FDA has examined the impacts of this final rule under Executive 
Order 12866. Executive Order 12866 directs Federal agencies to assess 
the 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 effects; distributive impacts; and equity). According 
to Executive Order 12866, a regulatory action is significant if it 
meets any one of a number of specified conditions, including having an 
annual effect on the economy of $100 million, adversely affecting in a 
material way a sector of the economy, competition, or jobs, or if it 
raises novel legal or policy issues. FDA finds that this final rule is 
not a significant regulatory action as defined by Executive Order 
12866. In addition, the agency has determined that this final rule is 
not a major rule for the purpose of Congressional review.
    The primary benefit of this action is to remove uncertainty about 
the regulatory status of the petitioned

[[Page 24419]]

substance. No compliance costs are associated with this final rule 
because no new activity is required and no current or future activity 
is prohibited by this rule.

VIII. Regulatory Flexibility Analysis

    FDA has examined the impacts of this final rule under the 
Regulatory Flexibility Act. The Regulatory Flexibility Act (5 U.S.C. 
601-612) requires Federal agencies to consider alternatives that would 
minimize the economic impact of their regulations on small entities. No 
compliance costs are associated with this final rule because no new 
activity is required and no current or future activity is prohibited. 
Accordingly, under the Regulatory Flexibility Act (5 U.S.C. 605(b)), 
the agency certifies that this final rule will not have a significant 
economic impact on a substantial number of small entities.

IX. References

     The following references have been placed on display in the 
Dockets Management Branch (address above) and may be seen by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday.
     1. Scott, D., ``Enzymes, Industrial,'' Encyclopedia of Chemical 
Technology, edited by Mark, H. F. et al., John Wiley and Sons, New 
York, 3d ed., 9:173-224, 1978.
    2. MacRae, A. R., ``Lipase-Catalyzed Interesterification of Fats 
and Oils,'' Journal of the American Oil Chemists Society, 60:291-
294, 1983.
    3. Ratledge, C., ``Biotechnology as Applied to the Oils and Fats 
Industry,'' Fette Seifen Anstrichmittel, 86:379-389, 1984.
    4. MacRae, A. R., and R. C. Hammond, ``Present and Future 
Applications of Lipases,'' Biotechnology and Genetic Engineering 
Reviews, 3:193-217, 1985.
    5. IUB, ``Enzyme Nomenclature 1992,'' Academic Press, New York, 
p. 307, 1992.
    6. Inui, T., Y. Takeda, and H. Iizuka, ``Taxonomical Studies on 
Genus Rhizopus,'' Journal of General and Applied Microbiology, 11:1-
121, 1965.
    7. Beckhorn, E. J., M. D. Labee, and L. A. Underkofler, 
``Production and Use of Microbial Enzymes for Food Processing,'' 
Journal of Agricultural and Food Chemistry, 13:30-34, 1965.
    8. Underkofler, L. A., R. R. Barton, and S. S. Rennet, 
``Microbiological Process Report--Production of Microbial Enzymes 
and Their Applications,'' Applied Microbiology, 6:212-221, 1958.
    9. Chibata, Ichiro, ed., Immobilized Enzymes--Research and 
Development, John Wiley and Sons, New York, 1978.
    10. Chaplin, M. F., and C. Bucke, Enzyme Technology, Cambridge 
University Press, New York, 1990.
    11. Shahani, K. M., ``Lipases and Esterases,'' Enzymes in Food 
Processing, edited by Reed, G., Academic Press, New York, 2d ed., 
pp. 208-214, 1975.
    12. Reed, G., ``Industrial Enzymes-Now Speed Natural 
Processes,'' Food Engineering, 24:105-109, 1952.
    13. De Becze, G. I., ``Food Enzymes,'' Critical Reviews in Food 
Technology, 1:479-518, 1970.
    14. Codex Alimentarius, Joint FAO/WHO Food Standards Programme, 
Food and Agriculture Organization of the United Nations/World Health 
Organization, Rome, vol. 1, 2d ed., 1992.
    15. Pariza, M. W., and E. M. Foster, ``Determining the Safety of 
Enzymes Used in Food Processing,'' Journal of Food Protection, 
46:453-468, 1983.
    16. Shils, M. E., J. A. Olson and M. Shike, eds., Modern 
Nutrition in Health and Disease, Lea & Febiger, Philadelphia, 8th 
ed., pp. 51-57, 1994.
    17. ``Evaluation of the Health Aspects of Papain as a Food 
Ingredient,'' Select Committee on GRAS Substances, Washington, DC, 
available through U.S. Department of Commerce, National Technical 
Information Service, Order No. PB-274-174, 1977.
    18. Fulwiler, R. D., ``Detergent Enzymes--An Industrial Hygiene 
Challenge,'' American Industrial Hygiene Association Journal, 32:73-
81, 1971.
    19. ``Enzyme-containing Laundering Compounds and Consumer 
Health,'' National Research Council/National Academy of Sciences, 
National Technical Information Service, Washington, DC, Order No. 
PB-204-118, 1971.
    20. Monograph on ``Enzyme Preparations,'' Food Chemicals Codex, 
National Academy Press, Washington, DC, 4th ed., pp. 131 and 133-
134, 1996.
    21. Memorandum dated October 21, 1988, from Food and Color 
Additives Review Section, FDA, to Direct Additives Branch, FDA, 
``Lipase/Protease Enzyme Preparation Derived from Rhizopus niveus.''
    22. Memorandum dated March 8, 1989, from Food and Color 
Additives Review Section, FDA, to Direct Additives Branch, FDA, 
``Lipase-Protease Enzyme Preparation from Rhizopus niveus.''
    23. Memorandum dated April 3, 1990, from Food and Color 
Additives Review Section, FDA, to Direct Additives Branch, FDA, 
``Lipase/Protease Enzyme Preparation from Rhizopus niveus. 
Refinement of Estimated Daily Intake (EDI). Submission of 3-6-90.''
    24. Monograph on ``Enzyme Preparations,'' Food Chemicals Codex, 
National Academy Press, Washington, DC, 4th ed., p. 803, 1996.

List of Subjects in 21 CFR Part 184

    Food additives, Incorporation by reference.
    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, 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: 21 U.S.C. 321, 342, 348, 371.
    2. Section 184.1420 is added to subpart B to read as follows:


Sec. 184.1420  Lipase enzyme preparation derived from Rhizopus niveus.

    (a) Lipase enzyme preparation contains lipase enzyme (CAS Reg. No. 
9001-62-1), which is obtained from the culture filtrate resulting from 
a pure culture fermentation of a nonpathogenic and nontoxigenic strain 
of Rhizopus niveus. The enzyme preparation also contains diatomaceous 
earth as a carrier. The characterizing activity of the enzyme, which 
catalyzes the interesterification of fats and oils at the 1- and 3-
positions of triglycerides, is triacylglycerol lipase (EC 3.1.1.3).
    (b) The ingredient meets the general requirements and additional 
requirements for enzyme preparations in the monograph on Enzyme 
Preparations in the ``Food Chemicals Codex,'' 4th ed. (1996), pp. 133 
and 134, which is incorporated by reference in accordance with 5 U.S.C. 
552(a) and 1 CFR part 51. Copies are available from the National 
Academy Press, 2101 Constitution Ave. NW., Washington, DC 20418, or may 
be examined at the Center for Food Safety and Applied Nutrition's 
Library, 200 C St. SW., rm. 3321, Washington, DC, or the Office of the 
Federal Register, 800 North Capitol St. NW., suite 700, Washington, DC.
    (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 as a 
direct human food ingredient is based upon the following current good 
manufacturing practice conditions of use:
    (1) The ingredient is used as an enzyme as defined in 
Sec. 170.3(o)(9) of this chapter for the interesterification of fats 
and oils.
    (2) The ingredient is used in food at levels not to exceed current 
good manufacturing practice.

    Dated: April 14, 1998.
L. Robert Lake,
Director, Office of Policy, Planning and Strategic Initiatives, Center 
for Food Safety and Applied Nutrition.
[FR Doc. 98-11681 Filed 5-1-98; 8:45 am]
BILLING CODE 4160-01-F