24416 Federal Register / Vol. 63, No. 85 / Monday, May 4, 1998 /Rules and Regulations

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.

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 § 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 § 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 (§ 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. niveusderived 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
Federal Register / Vol. 63, No. 85 / Monday, May 4, 1998 /Rules and Regulations 24417

1The stage of the manufacturing process in which

the enzyme is being produced by an actively

growing culture of microorganisms is referred to as

fermentation.

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. niveusderived 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. niveusderived 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 monoand 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 fermentation1 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 enzymecontaining fractions, and for

immobilizing an enzyme-containing

fraction on an insoluble carrier (Refs. 4

and 7 through 10).
24418 Federal Register / Vol. 63, No. 85 / Monday, May 4, 1998 /Rules and Regulations

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 batchfermentors 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 °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 enzymecontaining 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. niveusderived 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 enzymecatalyzed 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 § 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 (§ 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
Federal Register / Vol. 63, No. 85 / Monday, May 4, 1998 /Rules and Regulations 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:

§ 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 § 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 § 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