GRAS Notice 595 - Food and Drug Administration · gras notice (grn) no. 595 ... fduerqdwhg hqhuj\ iodyruhg srzghuhg dqg vsruwv gulqnv iodyruhg plon dqg plon gulqnv dqg

GRAS Notice (GRN) No. 595 http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/default.htm

ORIGINAL SUBMISSION

000001
http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/default.htm

PHARMA FOODS INTERNATIONAL CO.,LTD. 1-49 Goryo-Ohara, Nishikyo-ku, Kyoto 615-8245 Japan PHONE : +81-75-394-8605 FAX : +81 -75-394-8889

August 3, 2015

Office of Food Additive Safety (HFS-200) Center for Food Safety and Applied Nutrition Food and Drug Administration 5100 Paint Branch Parkway College Park, MD 207 40-3835

Dear Sir or Madam:

Re: GRAS Notice for gamma-Aminobutyric Acid (GABA)

In accordance with proposed 21 CFR 170.36 [Notice of a claim for exemption based on a Generally Recognized as Safe (GRAS) determination] published in the Federal Register [62 FR18938 (17 April1997)], I am submitting, as the notifier [Pharma Foods International Co., Ltd., 1-49 Goryo-Ohara, Nishikyo-Ku, Kyoto, 61 5-8245,Japan], a Notice of the determination, on the basis of scientific procedures, that gamma-Aminobutyric Acid (GABA) derived from L-glutamate via Lactobacillus hilgardii K-3 fermentation, produced by Pharma Foods International (PFI), as defined in the enclosed documents and CD-ROM, is GRAS under specific conditions of use as a food ingredient, and therefore, is exempt from the premarket approval requirements of the Federal, Food, Drug and Cosmetic Act. Information setting forth the basis for the GRAS determination, which includes detailed information on the notified substance, a summary of the basis for the GRAS determination, as well as a consensus opinion of an independent panel of experts in support of the safety of GABA under the intended conditions of use, also are enclosed for review by the agency.

I hereby certify that the enclosed electronic files for the GRAS Notice .for gammaAminobutyric Acid (GABA) entitled, "GRAS Exemption Claim for gamma-Aminobutyric acid (GABA) for Use as a Food Ingredient in the United States (U.S.)" were scanned for viruses prior to submission and is thus certified as being virus-free using McAfee VirusScan 8.8.

Should you have any questions or concerns regarding this GRAS Notice , please do not hesitate to contact me at any point during the review process so that we may provide a response in a timely manner.

Sincerely,

Noriko Horie Director of Sales & Marketing Pharma Foods International Co., ltd. 1-49 Goryo-Ohara, Nishikyo-Ku, Kyoto, 615-8245 Japan Email : [email protected] Office phone: +81 75 394 8600 Office fax: +81 75 394 0009 [PJ~~~u~~!Q)

AUG 6 2015

OFHCE OF FOOD ADDITIVE SAFETY

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(b) (6)

GRAS Exemption Claim for gamma-Aminobutyric acid (GABA) for Use as a Food Ingredient in the

United States (U.S.)

Submitted to: 2IILFHRI)RRG$GGLWLYH6DIHW\+)6 &HQWHUIRU)RRG6DIHW\DQG$SSOLHG 1XWULWLRQ&)6$1 )RRGDQG'UXJ$GPLQLVWUDWLRQ 3DLQW%UDQFK3DUNZD\ &ROOHJH3DUN0' 86$

Submitted by: 3KDUPD)RRGV,QWHUQDWLRQDO&R/WG *RU\R2KDUD1LVKLN\RNX .\RWR-DSDQ

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GAMMA-AMINOBUTYRIC ACID GRAS NOTICE

GRAS Exemption Claim for a gamma-Aminobutyric acid (GABA) for Use as a Food Ingredient in the

United States (U.S.)

Table of Contents Page

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List of Appendices

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List of Figures and Tables

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E. Basis for GRAS Determination

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F. Availability of Information

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II. Detailed Information Regarding the Identity of the Substance

A. Identity

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Common or Usual Name: *$%$

Chemical Name: gammaDPLQREXW\ULFDFLG

Chemical Abstracts Service (CAS) Number:

Empirical Formula: &+12

Molecular Weight:

Structural Formula: 6HH)LJXUH,,$

Figure II.A-1 Structure of gamma-Aminobutyric Acid (GABA)

Physical Properties

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Table II.A-1 Physical Properties of gamma-Aminobutyric Acid (GABA) Physical Property Value Temperature (C) Source 0HOWLQJ3RLQW & ([SHULPHQWDO

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B. Method of Manufacture

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were no objectionable conditions observed during the inspection86)'$ 7KH SURGXFWLRQIDFLOLW\LVDOVRFHUWLILHGXQGHU,62

Figure II.B-1 Schematic Overview of the Manufacturing Process for gamma-Aminobutyric Acid (GABA)

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Table II.B-1 List of Raw Materials and Processing Aids Used in the Manufacture ofGABA

Raw Material/Processing Aid Function 21 CFR Citation or GRAS Number Lactobacillus hilgardii . )HUPHQWDWLRQ

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Table II.C-1 Product Specifications for GABA Specification Parameter Specification Method of Analysis Identity $SSHDUDQFH /LJKW\HOORZWR

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Table II.C-2 Product Specifications for GABA 20 Specification Parameter Specification Method of Analysis Identity $SSHDUDQFH :KLWHWROLJKW\HOORZ

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Table II.C-3 Analysis of 3 Manufactured Lots of GABA Specification Parameter Specification Lot Number/Date of Manufacture

2J10/ 10/10/2012

4B06/ 2/6/2014

4E21/ 5/21/2014

Identity $SSHDUDQFH /LJKW\HOORZWROLJKWEURZQ

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Table II.C-5 Compositional Analysis of GABA Analysis Parameter Results (g/100 g) Method of Analysisa

Compositional Parameters gamma$PLQREXW\ULFDFLG $PLQRDFLGDQDO\VLVZLWK+3/&

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0RQRJO\FHULGHV 1' *DVFKURPDWRJUDSK\ TOTAL 101 Minerals 6RGLXPFKORULGH $WRPLFDEVRUSWLRQVSHFWURPHWHUPHWKRG

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&RSSHU 1' ,&3PHWKRG TOTAL MINERAL CONTENT 3.52

*$%$ gammaDPLQREXW\ULFDFLG+3/& KLJKSHUIRUPDQFHOLTXLGFKURPDWRJUDSK\

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



Table II.C-6 Detailed Amino Acid Analysis of GABA Analysis Parameter Results (g/100 g)a,

Total Amino Acids (Acid Hydrolysis)

Free Amino Acid Content Polypeptide Content

$UJLQLQH 1'

/\VLQH

+LVWLGLQH 1'

3KHQ\ODODQLQH 1'

7\URVLQH 1'

/HXFLQH 1'

,VROHXFLQH

0HWKLRQLQH

9DOLQH 1'

$ODQLQH 1'

*O\FLQH

3UROLQH 1'

*OXWDPLFDFLG

6HULQH

7KUHRQLQH

$VSDUWLFDFLG

7U\SWRSKDQ 1' 1' 1'

&\VWHLQH 1'

TOTAL 7.00 4.12 2.88 Total Amino Acid Content 7.00 7.00

*$%$ gammaDPLQREXW\ULFDFLG1' QRWGHWHFWHG D$PLQRDFLGDQGSRO\SHSWLGHDQDO\VLVZDVFRQGXFWHGXVLQJKLJKSHUIRUPDQFHOLTXLGFKURPDWRJUDSK\

(OLPLQDWLRQRIWKHVRXUFHRUJDQLVPL. hilgardii .IURPWKHILQDOSURGXFWLVDFKLHYHGWKURXJK WKHDSSHUWL]DWLRQSURFHVVDQGVXEVHTXHQWILOWHUVWHULOL]DWLRQVWHSV 0RUHRYHUODFWLFDFLGEDFWHULD VXFKDVL. hilgardii DUHKLJKO\VHQVLWLYHWRR[LGDWLYHHQYLURQPHQWVDQGWKXVLWLVXQOLNHO\WKDWWKH RUJDQLVPZRXOGVXUYLYHWKHR[LGDWLYHFRQGLWLRQVRIVSUD\GU\LQJIXUWKHUHQVXULQJWKDWPLFURELDO FRQWDPLQDWLRQRIL. hilgardii .LQWKHILQDOSURGXFWLVSUHYHQWHG $QDO\VLVRIWKHILQDO*$%$ LQJUHGLHQWFRQILUPHGWKHDEVHQFHRIL. hilgardii .VHH$SSHQGL[&$WWDFKPHQW& )XUWKHUPRUHLWLVQRWH[SHFWHGWKDWWKHIHUPHQWDWLRQFRQGLWLRQVZRXOGEHFRQGXFLYHWR FRQWDPLQDWLRQRIWKHILQDOSURGXFWZLWKL. hilgardii .GHULYHGELRJHQLFDPLQHVDVPDQ\RIWKH ELRJHQLFDPLQHSUHFXUVRUVKLVWLGLQHW\URVLQHDQGSKHQ\ODODQLQHZHUHGHWHFWHGDWPLQLPDO FRQFHQWUDWLRQVRIDQGDQDO\VLVRIWKH*$%$LQJUHGLHQWFRQILUPHGWKHDEVHQFHRI KLVWDPLQHVHH$SSHQGL[&$WWDFKPHQW& $GGLWLRQDOO\DQDO\VLVRIL. hilgardii . DVVRFLDWHGPLFURELDOE\SURGXFWVLQFOXGLQJHWK\OFDUEDPDWHDQGFLWUXOOLQHGHPRQVWUDWHGWKDWLW ZDVQRWGHWHFWHGLQ3),VILQDO*$%$LQJUHGLHQWVHH$SSHQGL[&$WWDFKPHQW&& UHVSHFWLYHO\



$QDO\VLVRIWKHEXONVWDELOLW\RI*$%$LQWHUPVRIWKH*$%$FRQWHQWDQGPRLVWXUHGHPRQVWUDWHG WKDWWKHILQDOSURGXFWZDVVWDEOHIRUDSHULRGRIXSWRZHHNVDWURRPWHPSHUDWXUH 7DEOH,,&

Table II.C-7 GABA Stability Following Storage at Room Temperature (20C) for 11, 17 and 18 Weeks

Lot Number Specification (%) Initial (%) After stored at 20C (%) Difference (%)

GABA Content

% ! DWZHHNV

/ DWZHHNV

. DWZHHNV

0RLVWXUH

% DWZHHNV

/ DWZHHNV

. DWZHHNV

*$%$ gammaDPLQREXW\ULFDFLG

%XONVWDELOLW\VWXGLHVDOVRLQGLFDWHWKDWWKH*$%$IRUPXODWLRQLVVWDEOHIRUXSWRPRQWKV XQGHUDPELHQWFRQGLWLRQV7DEOH,,& %DVHGRQWKLVWKHVKHOIOLIHZDVVHWDW\HDUV

Table II.C-8 Bulk Stability of GABA 20 Powder (Lot No. 4H11) Following Storage atRoom Temperature for a Period of 27 Months

Months 0 6 12 18 24 27 gamma$PLQREXW\ULF$FLG*$%$

*$%$ZDVDOVRGHWHUPLQHGWREHVWDEOHXQGHUFRQGLWLRQVUHSUHVHQWDWLYHRILWVLQWHQGHGXVHLQ IRRGVLQFOXGLQJDFRQFHQWUDWLRQRILQDTXHRXVVROXWLRQXQGHUYDULHGS+FRQGLWLRQVUDQJLQJ IURPWRDQGHOHYDWHGWHPSHUDWXUHVRIWR&)LJXUHV,,&WR,,& 7KXV*$%$LV H[SHFWHGWREHVWDEOHXQGHUWKHSURSRVHGFRQGLWLRQVRIXVHLQIRRGVDQGEHYHUDJHV



Figure II.C-1 Bulk Stability of GABA Powder (Lot No. 4H11) Under Heated Conditions Over a Period of 60 Minutes

Figure II.C-2 Stability of a 5% GABA Solution (Lot No. 4H11) Under Heated Conditions for a Period of 120 Minutes



Figure II.C-3 Stability of a 5% GABA Solution (Lot No. 4H11) Under Varied pH Conditions

III. Self-Limiting Levels of Use

7KHOHYHOVRIXVHRI*$%$DUHOLPLWHGGXHWRIRRGIRUPXODWLRQLVVXHVDVWKHLQJUHGLHQWLV H[SHFWHGWRLPSDUWDQXQGHVLUDEOHIODYRUWRWKHIRRGZKHQLQFRUSRUDWHGDWKLJKFRQFHQWUDWLRQV 6SHFLILFWKUHVKROGVIRUWKHVHHIIHFWVKDYHQRWEHHQGHWHUPLQHG

IV. Basis for GRAS Determination

'HWHUPLQDWLRQRIWKH*5$6VWDWXVRI*$%$LVRQWKHEDVLVRIVFLHQWLILFSURFHGXUHV ,QIRUPDWLRQ VXSSRUWLQJWKHJHQHUDOUHFRJQLWLRQRIWKHVDIHXVHRI*$%$LQFOXGHV

x 'DWDSHUWDLQLQJWRWKHLGHQWLW\LQWHQGHGXVHDQGHVWLPDWHGLQWDNHRI*$%$

x %DFNJURXQGRFFXUUHQFHRI*$%$DVDQDWXUDORUDGGHGFRPSRQHQWRIYDULRXVIRRGV FRQVXPHGLQWKH86DQG-DSDQLQFOXGLQJHVWLPDWHVRIEDFNJURXQGGLHWDU\H[SRVXUHV

x ,QIRUPDWLRQFKDUDFWHUL]LQJWKHNLQHWLFVDQGPHWDEROLFIDWHRI*$%$LQFOXGLQJGDWDRQWKH FDSDFLW\RI*$%$WRFURVVWKHEORRGEUDLQEDUULHUIURPWKHV\VWHPLFFLUFXODWLRQ

x 7KHHQWLUHW\RIDQLPDODQGKXPDQVWXGLHVDVVHVVLQJWKHVDIHW\RI*$%$FRQVXPSWLRQ DQG

x 'DWDSHUWDLQLQJWRWKHVDIHW\RIL. hilgardii .IRUXVHLQWKHSURGXFWLRQRIDIRRG LQJUHGLHQW

0RUHRYHUWKHVHGDWDZHUHUHYLHZHGE\D3DQHORI([SHUWVTXDOLILHGE\VFLHQWLILFWUDLQLQJDQG H[SHULHQFHWRHYDOXDWHWKHVDIHW\RI*$%$DVDFRPSRQHQWRIIRRGZKRFRQFOXGHGWKDWWKH



SURSRVHGXVHVRI*$%$DUHVDIHDQGVXLWDEOHDQGZRXOGEH*5$6EDVHGRQVFLHQWLILF SURFHGXUHV>VHH$SSHQGL[$Expert Panel Report Concerning the Generally Recognized as Safe (GRAS) Status of gamma-Aminobutyric Acid (GABA) for Use as a Food Ingredient@. $VXPPDU\RIWKHGDWDLVSUHVHQWHGKHUHLQ

A. Estimated Intake of GABA

Background Dietary Consumption of GABA

$VVKRZQLQ7DEOH,9$*$%$H[LVWVQDWXUDOO\LQPDQ\GLIIHUHQWIRRGVDWORZOHYHOVDQGLQ KLJKHUOHYHOVLQIHUPHQWHGIRRGSURGXFWV ([DPSOHVRI*$%$ULFKIRRGVLQFOXGHWRPDWRHV SRWDWRHVPHORQVDQGWKHWUDGLWLRQDO.RUHDQDQG-DSDQHVHIRRGNLPFKLDQGPLVR 7KHVHIRRGV KDYHEHHQUHSRUWHGWRFRQWDLQIURPWRPJ*$%$JIRRGSURGXFW6WHZDUGet al., )R[/RLXGLFHet al., +D\DNDZDet al., 0DWXPRWRet al., 1RPXUD et al., $NDVWX0XUFLDet al1DNDPXUDet al ,QDGGLWLRQVLQFHWKH FRQYHUVLRQRIJOXWDPDWHWR*$%$LVUHSRUWHGIRUPDQ\ODFWLFDFLGEDFWHULDRWKHUIRRGVDUHOLNHO\ WRFRQWDLQDSSUHFLDEOHDPRXQWVRI*$%$DVDUHVXOWRIWKHSURFHVVLQJPHWKRGVXVHGWRSURGXFH WKHPe.g.ODFWLFDFLGIHUPHQWHGIRRGVVXFKDVFXUHGPHDWVDQGFKHHVHV )RUH[DPSOH FHUWDLQFKHHVHVVXFKDV.RPSDQVLWLFKHHVHKDYHEHHQUHSRUWHGWRFRQWDLQOHYHOVRI*$%$DV KLJKDVPJJ

Table IV.A-1 Reported GABA Content of Various Foodsa

Food Item GABA Content (mg/100 g)


*UHHQ7HD/HDIGULHG WR &XFXPEHU

0HORQ 7RIX

7RPDWR 6R\EHDQJUHHQ

6DQ0DU]DQR7RPDWR &DUURW

.LPFKLIHUPHQWHG 5DGLVK

9HJHWDEOH-XLFH 3HUVLPPRQ

7RPDWR-XLFH *UHHQSHSSHU

0LVRVR\SDVWH *UHHQEHDQ

3RWDWR .LZL

.LPFKLOLJKWO\SLFNOHG 8QSROLVKHGULFH

*UDSHV /HWWXFH

(JJ3ODQW 3HDFK

0DQGDULQ2UDQJH 2QLRQ

5LFH9LQHJDU 6SLQDFK

&KRFRODWH &KLQHVHFDEEDJH

$PDQDWVXRUDQJH 5LFHSROLVKHG

1DYHORUDQJH 0LON

*HUPLQDWHGULFH &DQQHGFRIIHH



Table IV.A-1 Reported GABA Content of Various Foodsa



3XPSNLQ &KHGGDU

&DEEDJH *RXGD

6KLWDNHPXVKURRP 3DUPLJLDQRFKHHVH

/RTXDW .RPSDQLVWLFKHHVH

%URFFROL 3RWDWR7XEHU D$GDSWHGIURP6WHZDUGet al. )R[+D\DNDZDet al. 1DNDPXUDet al0DWXPRWRet al. $NDVWX1RPXUDet al. /RLXGLFHet al. 0XUFLDet alLQGHSHQGHQWDQDO\VLV FRQGXFWHGE\3KDUPD)RRGV,QWHUQDWLRQDO&R/WG

8VLQJDQQXDOper capita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

Food Uses of GABA World-Wide

0DQ\*$%$HQULFKHGIRRGVKDYHEHHQODXQFKHGRQWRWKH-DSDQHVHPDUNHWRYHUWKHSDVW \HDUVZLWKSRVLWLYHFRQVXPHUUHFHSWLRQ 3URGXFWVWKDWFXUUHQWO\DUHHQULFKHGZLWK*$%$LQ -DSDQLQFOXGHWHDJHUPLQDWHGULFHSURGXFWVSLFNOHVIHUPHQWHGPLONDQGFKRFRODWHDVGHWDLOHG LQ7DEOH,9$ 7KH*$%$FRQWHQWLQWKHVHSURGXFWVUDQJHVIURPDSSUR[LPDWHO\PJJ LQJHUPLQDWHGULFHWRPJJLQFKRFRODWH



Table IV.A-2 Examples of GABA-Enriched Foods and Beverages Currently Sold in Japan Food Product Name Manufacturer GABA Content Year Launched 7HD *$%5217($ 26.,.7 PJJ

*HUPLQDWHG5LFH 6SURXWHG%URZQ5LFH 'RPHU,QF PJJ

*HUPLQDWHG5LFH %URZQ5LFH +$768*$0$,

)$1&/&RUS PJJ

*HUPLQDWHG5LFH ([WUDFW

25


Table IV.A-3 Examples of Dietary Supplement Products in the U.S. Identified as Containing GABA as a Dietary Ingredient

Product Ingredient(s) [Form] Directions for Use

Amount of GABA (mg)/ serving

Daily Intake of GABA (mg)

$676SRUWV 6FLHQFH*$%$

*$%$>SRZGHU@ WRVFRRSV GDLO\

WR WR

%LRV\QHUJ\+HDOWK $OWHUQDWLYHV 1DWXUDO*$%$

*$%$PDJQHVLXPVWHDUDWH VLOLFRQGLR[LGHPDOWRGH[WULQ >FDSVXOH@

WRFDSVXOHV GDLO\

-DUURZ)RUPXODV *$%$6RRWKH

*$%$WKHDQLQH$VKZDJDQGKD H[WUDFWFHOOXORVHPDJQHVLXP VWHDUDWHVLOLFRQGLR[LGH>FDSVXOH@

FDSVXOHGDLO\

-DUURZ)RUPXODV 6OHHS2SWLPL]HU

*$%$/WU\SWRSKDQOHPRQEDOP KRSVIORZHUPHODWRQLQ PDJQHVLXPVWHDUDWHVLOLFRQ GLR[LGH>FDSVXOH@

FDSVXOHVGDLO\ EHIRUHEHGWLPH

.$/*$%$ *$%$YDULRXVILOOHUV>WDEOHW@ WDEOHWGDLO\

6ZDQVRQ+HDOWK 3URGXFWV*$%$

*$%$JHODWLQPDJQHVLXP VWHDUDWH>FDSVXOH@

FDSVXOHGDLO\

6RXUFH1DWXUDOV *$%$

*$%$>FDSVXOHRUWDEOHW@ WDEOHWGDLO\

7ZLQ/DEV*$%$ 3OXV

*$%$QLDFLQLQRVLWROVLOLFD PDJQHVLXPDQGILOOHUV>FDSVXOH@

WRFDSVXOHV GDLO\

8OWLPDWH1XWULWLRQ *$%$

*$%$&HOOXORVHGLFDOFLXP SKRVSKDWHJHODWLQDQG PDJQHVLXPVWHDUDWH>FDSVXOH@

WDEOHWVGDLO\

9LWDPLQ6KRSSH *$%$

*$%$YDULRXVILOOHUV>FDSVXOH@ WDEOHWGDLO\

Intended Conditions of Use of PFIs GABA in Food and Proposed Levels of Use

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



Table IV.A-4 Summary of the Individual Proposed Food-Uses and Use-Levels for gamma-Aminobutyric Acid (GABA) in the U.S. (NHANES 2011-2012 Data)

Food Category Food-Uses Serving Sizea Proposed Use Level (per serving) (%)

%DNHG*RRGVDQG%DNLQJ 0L[HV

6QDFN%DUV J PJ

%HYHUDJHVDQG%HYHUDJH %DVHV

&DUERQDWHG'ULQNV P/ PJ

(QHUJ\'ULQNVLQFOXGLQJVKRW GULQNVE

P/P/F PJ

)ODYRUHG'ULQNV P/ PJ

3RZGHU'ULQNVLQFOXGLQJ SURWHLQSRZGHU

P/ PJ

6SRUWV'ULQNV,VRWRQLF'ULQNV P/ PJ

%UHDNIDVW&HUHDOV %UHDNIDVW&HUHDOV JSXIIHG JH[WUXGHG JELVFXLW

PJ

&KHHVHV 3URFHVVHG&KHHVHG J PJ

&KHZLQJ*XP &KHZLQJ*XP J PJ

&RIIHHDQG7HD &RIIHH6SHFLDOW\&RIIHHDQG ,QVWDQW&RIIHH

P/ PJ

7HDDQG,QVWDQW7HD P/ PJ

+DUG&DQG\DQG&RXJK 'URSV

&DQGLHV+DUG J PJ

0LON3URGXFWV )ODYRUHG0LONDQG0LON'ULQNV P/ PJ


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

Table IV.A-5 Summary of the Estimated Daily Intake of gamma-Aminobutyric Acid (GABA) from Proposed Food-Uses in the United States by Population Group (NHANES 2011-2012 Data)

Population Group Age Group (Years)

All-Person Consumption (mg/person/day)

All-Users Consumption (mg/person/day)

Mean 90th

Percentile %

Users n Mean 90th

Percentile ,QIDQWV WR

&KLOGUHQ WR

)HPDOH7HHQDJHUV WR

0DOH7HHQDJHUV WR

)HPDOH$GXOWV DQGXS

0DOH$GXOWV DQGXS

7RWDO3RSXODWLRQ $OO$JHV

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



Table IV.A-6 Summary of the Estimated Daily Per Kilogram Body Weight Intake of gamma-Aminobutyric Acid (GABA) from Proposed Food-Uses in the United States by Population Group (NHANES 2011-2012 Data)

Population Group Age Group (Years)

All-Person Consumption (mg/kg bw/day)

All-Users Consumption (mg/kg bw/day)

Mean 90th

Percentile %

Users n Mean 90th

Percentile

,QIDQWV WR

&KLOGUHQ WR

)HPDOH7HHQDJHUV WR

0DOH7HHQDJHUV WR

)HPDOH$GXOWV DQGXS

0DOH$GXOWV DQGXS

7RWDO3RSXODWLRQ $OO$JHV

EZ ERG\ZHLJKW

B. Pharmacokinetics and Metabolic Fate

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Pharmacokinetics

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H. Information Pertaining to the Safety of the Source Organism

Description of the Source Organism, L. hilgardii K-3

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Safety of L. hilgardii in Foods

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GRAS Notice 595 - Food and Drug Administration · gras notice (grn) no. 595 ... fduerqdwhg hqhuj\ iodyruhg srzghuhg dqg vsruwv gulqnv iodyruhg plon dqg plon gulqnv dqg