Clinical 

Research 

Laboratories, Inc. 

Report Status: 

Report Date: 

CRL Study Number: 

Client Study Number: 

CRL Protocol Number: 

Study Dates: 

Study Title: 

Test Material: 

Sponsor: 

Sponsor Representative: 

Investigator: 

APPROVAL SIGNATURES: 

Anita Lee Cham, M.D. 

Dermatologist 

Final Report 

December 12,2014 

CRL81314-1 

FRET 09-0536-01 

CL 1.0 2014 

October 27,2014- December 5, 2014 

Repeated Insult Patch Test (RIPT) --Shelanski Method 

FRET 09-0536-01 (2% in EtOH:DEP(1 :3)) 

International Flavors & Fragrances Inc. 

800 Rose Lane 

Union Beach, NJ 07735 

Paul Sterchele, PhD 

Senior Regulatory Toxicologist 

Global Regulatory Affairs 

Anita Lee Cham, M.D. 

Dermatologist 

Date 

371 Hoes Lane, Suite 100 • Piscataway, NJ 08854 • (732) 981-1616 • FAX (732} 981-0520 
Clinical 

Research 

Laboratories, Inc. 

·······•· •·•·· .. ·. ·• •· . G66a ctiD.ical Practic(! ·.• · . ·. · . ·· · QualitY ~$~t.r1tll¢~.~~Qft Statement 

Clinical Study Number: CRL81314-l 

Start Date: October 27, 2014 

Completion Date: December 5, 2014 

The clinical study listed above was conducted in accordance with Clinical Research 

Laboratories, Inc. Standard Operating Procedures, which incorporate the principles of 

Good Clinical Practice defined by applicable guidelines and regulations established by 

U.S. Regulatory Agencies. The conduct of the study was monitored for compliance, and 

the associated records, including source documents or raw data, were reviewed for 

documentation practices and accuracy by a Project Manager/Study Director and/or a 

Quality Assurance Representative. Standard Quality Assurance audit procedures for this 

final report and study related documents were conducted. 

The Project Manager verifies that the clinical study listed above was executed according 

to the study protocol and all documentation contained in the study file accurately reflects 

the conduct of the study. 

/~gill(ture of Project Manager Date 

lv-j,,_j 1 '-" 

&~. 12; ).cJ/f 

Date 
Clinical 

Final Report 

Sponsor: llltematimta/ Flavors & Fragrances Inc. 

Study Number: CRL813U~J 

Page3ofl4 

Research 

Laboratories, Inc. 

FINAL REPORT 

Repeated Insult Patch Test (RIPD- Shelanski Method 

1.0 SUMMARY 

One hundred twelve subjects participated in evaluating the potential of FRET 09-

0536-01 (2% in EtOH:DEP(l:3)) to elicit dermal irritation and/or induce 

sensitization. The test material was applied under an occlusive patch to the upper 

back of each subject and was allowed to remain in direct skin contact for a period of 

24 hours. Patches were applied to the same site on Monday, Wednesday, and 

Friday for a total of 9 applications during the Induction Period. The sites were 

graded by a CRL technician for dermal irritation 24 hours after removal of the 

patches by the subjects on Tuesday and Thursday and 48 hours after removal of the 

patches on Saturday 

Following approximately a 2-week rest period, challenge patches were applied to 

previously untreated test sites on the back. After 24 hours, the patches were 

removed by a CRL technician and the test sites were evaluated for dermal reactions. 

The test sites were re-evaluated at 48 and 72 hours. Subjects exhibiting reactions 

during the Challenge Phase of the study may have been asked to return for a 96-

ho\lr reading. 

One hundred subjects completed the study. The test material identified as FRET 

09-0536-01 (2% in EtOH:DEP(l :3)) did not demonstrate a potential for eliciting 

dermal irritation or sensitization under the following test conditions: 0.2ml of the 

test material applied to a 3.63 cm

2 occlusive patch. 

2.0 OBJECTIVE 

The objective of this study was to determine the dermal irritation and sensitization 

potential of a test material. 

3.0 INVESTIGATOR/INVESTIGATIVE SITE 

Anita Lee Cham, M.D. 

Dermatologist 

Clinical Research Laboratories, Inc. 

371 Hoes Lane, Suite 100 

Piscataway, New Jersey 08854 

732-981-1616 

4.0 SPONSOR REPRESENTATIVE/SPONSOR 

Paul Sterchele, PHD 

Senior Regulatory Toxicologist 

Global Regulatory Affairs 

International Flavors & Fragrances Inc. 

800 Rose Lane 

Union Beach, NJ 07735 
Filla/ Report 

Clinical SpoiiSor: lntemational Flavors&: Fragra11ces file. 

Study Number: CRL81314-l 

Research 

Laboratories, Inc. 

5.0 TEST MATERIAL 

Page4ofl4 

The following test material was provided by International Flavors & Fragrances Inc. 

and was received by Clinical Research Laboratories, Inc. on. 

Test Material Test Condition Patch Type 

FRET 09-0536-01 

0.2 ml of the test material was applied to a 

3.63cm2 patch. The test material was applied to 

(2%in the patch as received and allowed to evaporate Occlusive* 

EtOH:DEP(1 :3)) for at least 30 minutes, but no longer than 90 

minutes, prior to patch application. 

The test material was coded with the following CRL identification number: 

CRL81314-1 

6.0 STUDY DATES 

This study was initiated on October 27, 2014 and was completed on December 5, 2014. 

7.0 PANEL SELECTION 

Each subject was assigned a permanent CRL identification number. All subjects 

signed an Informed Consent Form in compliance with 21 CFR Part 50: "Protection 

of Human Subjects" and a HIPAA Authorization Form in compliance with 45 CFR 

Parts 160 and 164. All subjects completed a Subject Profile/Medical History Form 

provided by Clinical Research Laboratories, Inc. prior to the study (Subject 

Demographics - Appendix I). Subjects who met the following Inclusion Criteria 

and none of the Exclusion Criteria were impaneled: 

7.1. INCLUSION CRITERIA 

a. Subject is male or female between the ages of 18 and 70 years; 

b. Subjects with no visible or known pre-existing skin diseases that might be 

confused with a skin reaction from the test material, or which may be reasonably 

expected to affect the outcome of the study. This includes subjects with 

psoriasis or active eczema, even if currently controlled through medication; 

c. Subjects who do not report a history of acute or chronic dermatologic, medical, 

or physical conditions that could interfere with dermal scoring; 

d. Subject agrees to avoid exposure of the test sites to the sun and to refrain from 

visits to tanning salons during the course of this study; 

e. Subject agrees to refrain from getting patches wet during the course of the study; 

*Occlusive Strip with Flexcon® (Strukmyer LLC, Mesquite,TX or equivalent) 
Clinical 

Research 

Laboratories, Inc. 

7.0 PANEL SELECTION (Continued) 

7.1 INCLUSION CRITERIA (CONTINUED) 

Final Report 

Spo11sor: IJtternat/onal Flavors & Fragra11ces Inc. 

Stul(y Number: CRL81314-l 

PageS ofl4 

f. Subject has signed an Informed Consent in conformance with 21CFR Part 50: 

"Protection of Human Subjects;" 

g. Subject has completed a HIPAA Authorization Form in conformance with 45CFR 

Parts 160 and 164; 

h. Subject is in generally good health and has a current Subject Profile/Medical 

History on file; 

1. Subject is dependable and able to follow directions as outlined in the protocol. 

7.2. EXCLUSION CRITERIA 

a. Subject is pregnant, nursing, or planning to become pregnant; 

b. Subject is currently using any systemic or topical corticosteroids, antiinflammatory drugs, or antihistamines on a regular basis; 

c. Subject reports anergies to cosmetics, toiletries, or personal care products; 

d. Subject exhibits any skin disorders, sunburn, scars, excessive tattoos, etc. in the 

test area; 

e. Subject has scheduled, or is planning to undergo, any medical or surgical 

procedures during the 6 week course of the study. 

f. Subjects who have reacted to an IFF test material within the past year. 

8.0 TEST METHOD SUMMARY 

This study was conducted using a modified Shelanski - Shelanski human patch test 

method'. Prior to the application of the patch, the test area was wiped with 70% 

isopropyl alcohol and allowed to dry. The test material, which was prepared as 

described in the Test Material section of the report, was applied to the upper back 

(between the scapulae) and was aU owed to remain in direct skin contact for a period 

of24 hours. 

Patches were applied to the same site on Monday, Wednesday, and Friday for a total 

of 9 applications during the Induction Period. This schedule may have been 

modified to allow for missed visits or holidays. If a subject was unable to report on 

an assigned test date, the test material was applied on 2 consecutive days during the 

Induction Phase and/or a makeup day was added at the end of the Induction Phase. 

*H.A. Shelanski and M.V. Shelanski, Proc. Sci. Sect. Toilet Goods Assoc. 19:46, 1953. 
Clinical 

Final Report 

Sponsor: Internatiomrl Flavors & Fragrances Inc. 

Stndy Nttmber: CRL81314-I 

Page6ofl4 

Research 

Laboratories, Inc. 

8.0 TEST METHOD SUMMARY (Continued) 

The sites were graded by a CRL technician for dermal irritation 24 hours after 

removal of the patches by the subjects on Tuesday and Thursday and 48 hours after 

removal of the patches on Saturday, unless the patching schedule was altered as 

described above. 

The sites were graded according to the following scoring system: 

Dermal Scoring Scale 

0 No visible skin reaction 

± Barely perceptible erythema 

1 + Mild erythema 

2+ Well defmed erythema 

3+ Severe erythema and edema 

4+ Erythema and edema with vesiculation 

If a "2+" reaction or greater occurred, the test material was applied to an adjacent 

virgin site. If a "2+" reaction or greater occurred on the new site, the subject may 

not have been patched again during the Induction Phase but may have been 

challenged on the appropriate day of the study. At the discretion of the Study 

Director, patch sites with scores less than a "2+"may have been changed. 

Following approximately a 2-week rest period, the challenge patches were applied 

to previously untreated test sites on the back. After 24 hours, the patches were 

removed by a CRL technician and the test sites were evaluated for dermal reactions. 

The test sites were re-evaluated at 48 and 72 hours. Subjects exhibiting reactions 

during the Challenge Phase of the study may have been asked to return for a 96-

hour reading. 

9.0 RESULTS 

This study was initiated with 112 subjects. Twelve subjects discontinued study 

participation for reasons unrelated to the test material. A total of 100 subjects 

completed the study. 

Individual dermal scores recorded during the Induction and Challenge Phases 

appear in Table I. 

10.0 ADVERSE EVENTS 

No adverse events were reported during the study. 
Clinical 

Research 

Laboratories, Inc. 

11.0 CONCLUSION 

Final Report 

Sponsor: Intemational Flavors&. Fragrances lttc. 

Study Number: CRL81314-l 

Page 7ofl4 

Based on the test population of 100 subjects and under the conditions of this study, 

the test material identified as FRET 09-0536-01 (2% in EtOH:DEP(l :3)) did not 

demonstrate a potential for eliciting dermal irritation or sensitization under the 

following test conditions: 0.2ml of the test material applied to a 3.63 cm

2 occlusive 

patch. 

12.0 RETENTION 

Test materials and all original forms of this study will be retained by Clinical 

Research Laboratories, Inc. as specified in CRL Standard Operating Procedures 

30.6 and 30.6C, unless designated otherwise by the Sponsor. 
Clinical 

Research 

Laboratories, Inc. 

TABLE I 

Summary of Dermal Scores 

FiJ~al Report 

Sponsor: lnlenzational Flavors & Fragrances fire. 

Study Number: CRL8131-t.l 

Page8ofl4 

II .• T~tl\{aterial:·l FRET 09-0536-01 (2% in EtOH:DEP(l :3)) 

SulfttL . •. . ······ .. Challenge Scores · · · Inductioll Scores • · ' .. 

. . J .. ·. 24 48: 7Z . :Nuilibt1r. ·r . . 2 . 3 .·· . -.:4 . s .ii . 1. 8 .9 . 

••••• }lQur. HQ~r }JQur 

1 0 0 0 0 0 0 0 0 0 0 0 0 

2 0 0 0 0 0 0 0 0 0 0 0 0 

3 0 0 0 0 0 0 0 0 0 0 0 0 

4 0 0 0 0 0 0 0 0 0 0 0 0 

5 0 0 0 0 0 0 0 0 0 0 0 0 

6 0 0 0 0 0 0 0 0 0 0 0 0 

7 0 0 0 0 0 0 0 0 0 0 0 0 

8 0 0 0 0 0 0 0 0 0 0 0 0 

9 0 0 0 0 0 0 0 0 0 0 0 0 

10 0 0 0 0 0 0 0 0 0 0 0 0 

11 0 0 0 0 0 0 0 0 0 0 0 0 

12 0 0 0 0 0 0 . 0 0 0 0 0 0 

13 0 0 0 0 0 0 0 0 0 0 0 0 

14 0 0 0 0 0 0 0 0 0 0 0 0 

15 0 0 0 0 0 0 0 0 0 0 0 0 

16 0 0 0 0 0 0 0 0 0 0 1+ 0 

17 0 0 0 0 0 0 0 0 0 0 0 0 

18 0 0 0 0 0 0 0 0 0 0 0 0 

19 0 0 0 0 0 0 0 0 0 0 0 0 

20 0 0 0 0 0 0 0 0 0 0 0 0 

21 OHr OHr 0 0 0 0 0 0 0 0 0 0 

22 0 0 0 0 0 0 0 0 0 0 0 0 

23 0 0 0 0 0 0 0 0 0 0 0 0 

24 0 0 0 0 0 0 0 0 0 0 0 0 

25 0 0 0 0 0 0 0 0 0 0 0 0 

Hr- Hyperp1gmentation 
Clinical 

Research 

Laboratories, Inc. 

TABLE I 

(Continued) 

Summary of Dermal Scores 

Final Report 

Sponsor: International FlaPors & Fragraltces I11c. 

Study Number: CRL81J14-1 

Page9ofl4 

: j:!iStMalerial: I FRET 09-0536-01 (2% in EtOH:DEP(1:3)) 

... .. . .. , .. ··.··· · · • ·• . .Induction Scores · · · .·· · · Cl!all¢nge Scores ·.Subject ·· . .............•. · . . . 

... '·· A :s.:: ............ I f •.• · 

u .. 48 72 ,Nll~bef •. l. 2 3 .;•.v: ... .s 9 R9J~r. RoJ~r Ho.ur .... 

26 0 0 0 0 0 0 0 0 0 0 0 0 

27 0 0 0 0 0 0 0 0 0 0 0 0 

28 Discontinued 

29 0 0 0 0 0 0 0 0 0 0 0 0 

30 0 0 0 0 0 0 0 0 0 0 0 0 

31 0 0 0 0 0 0 0 Discontinued 

32 0 0 0 0 0 0 0 0 0 0 0 0 

33 0 0 0 0 0 0 0 0 0 0 0 0 

34 0 0 0 0 0 0 0 0 0 0 0 0 

35 0 0 0 0 0 0 0 0 0 0 0 0 

··36 0 0 0 0 • 0 0 0 0 ... 0 0 0 .. 0 

37 0 0 0 0 0 0 Discontinued 

38 0 0 0 0 0 0 0 0 0 0 0 0 

39 0 0 0 0 0 0 0 0 0 0 0 0 

40 0 0 0 0 0 0 0 0 0 0 0 0 

41 0 0 0 0 0 0 0 0 0 0 0 0 

42 0 0 0 0 0 0 0 0 0 0 0 0 

43 0 0 0 0 0 0 0 0 0 0 0 0 

44 0 0 0 0 0 0 0 0 0 0 0 0 

45 0 0 0 0 0 0 Discontinued 

46 0 0 0 0 0 0 0 0 0 0 0 0 

47 0 0 0 0 0 0 0 0 0 0 0 0 

48 0 0 0 0 0 0 0 0 0 0 0 0 

49 0 0 0 0 0 0 0 0 0 0 0 0 

50 0 0 0 0 0 0 0 0 0 0 0 0 
''''''''''''''''''' 

Clinical 

Research 

Laboratories, Inc. 

TABLE I 

{Continued) 

Summary of Dermal Scores 

Final Report 

Sponsor: International Flavors & FragraJJces l11c. 

Sttufy Number: CRL81314-1 

Page !Oo/14 

> .• · TI\Stl\'tat~ri~h I FRET 09-0536-01 (2% in EtOH:DEP(1:3)) 

' ~*J>jt~f ' • ': :. lndntti~JitScores ..... · . ' 

' Challenge Score$. 

Nllmbet- 1 .2 3 4 5 :'I 6 .-10 '8 9· 

24. ' 48 7'2 

Hout llour lJour 

51 0 0 0 0 0 0 0 0 0 0 0 0 

52 0 0 0 0 0 0 0 0 0 0 0 0 

53 0 0 0 0 0 0 0 0 0 0 0 0 

54 0 0 0 0 0 0 0 0 0 0 0 0 

55 0 0 0 0 0 0 0 0 0 0 0 0 

56 0 0 0 0 0 0 0 0 0 0 0 0 

57 0 0 0 0 0 0 0 0 0 0 0 0 

58 0 0 0 0 0 0 0 0 0 0 0 0 

59 0 0 0 0 0 0 0 0 0 0 0 0 

60 0 0 0 0 0 0 0 0 0 0 0 0 

61 0 0· 0 0 0 0 0 0 .... I 0 0 0 0 

62 0 0 0 0 0 0 0 0 0 0 0 0 

63 0 0 0 0 0 0 0 0 0 0 0 0 

64 0 0 0 0 0 0 0 0 0 0 0 0 

65 0 Discontinued 

66 0 0 0 0 0 0 0 0 0 0 0 0 

67 0 0 0 0 0 0 0 0 0 0 0 0 

68 0 0 0 0 0 0 0 0 0 0 0 0 

69 0 0 0 0 0 0 0 0 0 0 0 0 

70 0 0 0 0 0 0 0 0 0 0 0 0 

71 0 0 0 0 0 0 0 0 0 0 0 0 

72 0 0 0 Discontinued 

73 0 0 0 0 0 0 0 0 0 0 0 0 

74 0 0 0 0 0 0 0 0 0 0 0 0 

75 0 0 0 0 0 0 0 0 0 0 0 0 
.................. 

Clinical 

Research 

Laboratories, Inc. 

TABLE I 

(Continued) 

Summary of Dermal Scores 

Final Report 

Sponsor: Intemationa/ Flavors & Fragrances Juc. 

StudyNumber: CRLS/314-1 

PagellofU 

. ·.; . ······· .. · .• . .• • Test Material: FRET 09-0536-01 (2% in EtOH:DEP(l:3)) 

- - - . . . .•.·•···•····· :>J:~du¢ti~~;~¢~r~;r.•··.·····•·.· . · Challenge Scores Su~jeci ; . ;·; 

· N~m!Jer •. 3 ••. )<I ..... : ,..,. (.8 .. 

·.· 9 24. 48 72 l z .s • •6 

•••• . · .. Jio~n Hour Hour 

76 0 0 0 0 0 0 0 0 0 0 0 0 

77 0 0 0 0 0 0 0 0 0 0 0 0 

78 0 Discontinued 

79 0 0 0 0 0 0 0 0 0 0 0 0 

80 0 0 0 0 0 0 0 0 0 0 0 0 

81 0 0 0 0 0 0 0 0 0 0 0 0 

82 0 0 0 0 0 0 0 0 0 0 0 0 

83 0 0 0 0 0 0 0 0 0 0 0 0 

84 0 0 0 0 0 Discontinued 

85 0 0 0 0 0 0 0 0 0 0 X 0* 

86 . . ... . . . · · Discontinued 

87 0 0 0 0 0 0 0 0 0 0 0 0 

88 0 0 0 0 0 0 0 0 0 0 0 0 

89 0 0 0 0 0 0 0 0 0 0 0 0 

90 0 0 0 0 0 Discontinued 

91 0 0 0 0 0 0 0 0 0 0 0 0 

92 0 0 0 0 0 0 0 0 0 0 0 0 

93 0 0 0 0 0 0 0 0 0 0 0 0 

94 0 0 0 0 0 0 0 Discontinued 

95 0 0 0 0 0 0 0 0 0 0 0 0 

96 0 0 0 0 0 0 0 0 X Discontinued 

97 0 0 0 0 0 0 0 0 0 0 0 0 

98 0 0 0 0 0 0 0 0 0 0 0 0 

99 0 0 0 0 0 0 0 0 0 0 0 0 

100 0 0 0 0 0 0 0 0 0 0 0 0 

X- Subject Absent 

*No reaction was observed at the 96 hour evaluation 
'''''''''' 

Clinical 

Research 

Laboratories, Inc. 

TABLE I 

(Continued) 

Summary of Dermal Scores 

Final Report 

Sponsor: ltltemational Flavors & Fragrances Inc. 

Study Number: CRL813U-1 

Pagel1ofl4 

Test Material! I FRET 09-0536-0 I (2% in EtOH:DEP(l :3)) 

' .' ' .. ' : ' ..... Induction Scor¢$ < · --- ChallengeS:co~ --_ Subject' . ............ ----------- -. 

:Nilillb~r 3 ...... 

:t·•_.: -~- ··_ ._.· ····,··· 

_24: ' :-48 72 1 2 'A: : --7> 8 9 Hour Hour Hour 

101 0 0 0 0 0 0 0 0 0 0 0 0 

102 0 0 0 0 0 0 0 0 0 0 0 0 

103 0 0 0 0 0 0 0 0 0 0 0 0 

104 0 0 0 0 0 0 0 0 0 0 0 0 

105 0 0 0 0 0 0 0 0 0 0 0 0 

106 0 0 0 0 0 0 0 0 0 0 0 0 

107 0 0 0 0 0 0 0 0 0 0 0 0 

108 0 0 0 0 0 0 0 0 0 0 0 0 

109 0 0 0 0 0 0 0 0 0 0 0 0 

110 0 0 0 0 0 0 0 0 0 0 0 0 

Ill 0 0 0 0 0 0 0 0 o- 0 0 0 

112 0 0 0 0 0 0 0 0 0 0 0 0 

' 
· Subj¢ct. 

.Number 

1 

2 

3 

4 

5 

6 

7 

8 

9 

10 

11 

12 ... 

13 

14 

15 

16 

17 

18 

19 

20 

21 

22 

23 

24 

25 

26 

27 

28 

Clinical 

Research 

Laboratories, Inc. 

Appendix I 

Subject Demographics 

Subject . cJU.,< '.Ag~ s~x •Iliifutls . mil-· Sub feet 

Nliinl>~~r 

DN 33175 34 F 29 

MC 02025 33 F 30 

BW 17003 64 F 31 

JB 14759 63 F 32 

JD 11122 53 F 33 

MS 13309 35 F 34 

DB 32989 56 F 35 

KT 31548 64 F 36 

ER 30633 56 F 37 

RV 08103 37 F 38 

BS 28576 61 F 39 

KW 30192 64 F 40 

SL 18114 38 F 41 

DL 25050 43 F 42 

TL 33407 42 F 43 

RP 31532 63 M 44 

FP 24056 59 F 45 

GK 18831 29 M 46 

AE 29803 31 M 47 

MC 28585 38 F 48 

JG 27625 63 F 49 

MB 18220 67 F so 

DG 01828 56 F 51 

AG 32545 57 F 52 

WB 30469 64 M 53 

ss 27553 57 F 54 

AA 32652 60 M 55 

RT 31341 51 F 56 

Final Report 

Sponsor: lntemational Flavors & Fragra11ces Inc. 

Study Number: CRL813U-I 

Pagel3ofl4 

Subject· ·cRt Age Sex Initials <iD# 

BB 01668 51 F 

TA 33389 46 F 

JB 25556 38 M 

PR 05291 52 F 

CM 00741 69 F 

JG 24987 54 M 

JA 05348 65 F 

ED 20237 55 F 

DM 15909 59 F 

DM 27962 57 F 

DT 32525 66 F 

CR 29212 46 F 

JS 30187 53 F 

AB 23147 49 F 

NI 33422 20 F 

DL 09278 54 F 

MO 33415 55 F 

IN 03306 69 F 

DR 31032 52 F 

AC 33413 22 F 

CN 27549 52 F 

BW 27548 67 F 

DP 32402 63 F 

CA 33435 55 M 

MR 31934 18 M 

MV 02437 68 F 

uw 33434 50 F 

CM 19646 56 F 
$ubject 

Number 

57 

58 

59 

60 

61 

62 

63 

64 

65 

66 

67 

68 

69 

70 

71 

72 

73 

74 

75 

76 

77 

78 

79 

80 

81 

82 

83 

84 

Clinical 

Research 

Laboratories, Inc. 

·Subject cRt· 

fuitia]s . ID#. 

GK 03981 

NC 10624 

MT 30825 

FT 28815 

AD 32492 

NC 33362 

NP 30154 

ER 33363 

SH 33411 

AS 33436 

LR 33408 

AM 32178 

CB 33196 

AC 19727 

PT 31460 

CR 09622 

JR 29685 

CB 24697 

GF 23083 

JB 29335 

ss 06517 

WM 33214 

HG 33133 

JH 19225 

TC 29284 

SK 18539 

LJ 33022 

LN 24351 

Appendix I 

Subject Demographics 

(Continued) 

Age sex S!!b'ect L 

.Nl!mber . 

63 F 85 

36 F 86 

24 F 87 

45 F 88 

54 F 89 

51 F 90 

28 M 91 

44 M 92 

41 F 93 

18 M 94 

34 F 95 

38 F 96 

54 F 97 

29 F 98 

54 F 99 

56 F 100 

67 F 101 

62 F 102 

51 F 103 

58 F 104 

59 F 105 

37 M 106 

56 M 107 

50 M 108 

34 F 109 

62 F 110 

34 M 111 

48 F 112 

Final Report 

Sponsor: lntemationat Flavors & FragratiCes Inc. 

Study Number: CR£81314-I 

Page l4ofl4 

>s~~ject . CRL ... ··Age Sex 

•. Ibitials . ···lD# 

PN 03277 57 F 

ER 33438 22 M 

LJ 28423 45 F 

DC 20624 61 F 

RC 31248 21 M 

JL 31000 49 F 

PS 31629 56 F 

MP 33431 20 F 

cw 16399 54 F 

JW 32123 39 F 

KH 33439 25 M 

BT 33424 42 M 

JP 22148 39 F 

RE 26689 42 M 

AA 29940 20 F 

DW 20399 54 F 

RJ 26063 52 F 

NF 14449 58 F 

BC 30844 23 F 

AS 02343 65 F 

TM 30142 46 F 

JG 16720 29 F 

JN 30414 32 F 

JS 24960 53 F 

ST 27390 56 F 

KB 32105 41 F 

DL 27410 53 F 

AM 13130 48 F 
HRIPT FRET 09-0536 

TEST SAMPLE 

Sample preparation: R&D (Gary Mertz) 

Request date: September 17,2014 

Test Chemical: FRET 09-0536 

Test Article FRET 09-0536-01, 2% w/w in Ethanol:DEP [25:75] 

8 

98 

294 

400 

g 

g 

g 

g 

FRET 09-0536 

Ethanol 

Diethyl Phthalate (043615) 

Total 

Final FRET 08-0338 Concentration= 8/400 (2% w/w) 

Test Article FRET 09-0536-02, 2% w/w in Ethanol:DEP [25:751 

8 

98 

294 

400 

g 

g 

g 

g 

Distilled water 

Ethanol 

Diethyl Phthalate (043615) 

Total 

Final Distilled Water Concentration= 8/400(2%w/w) 

PFS 
Clinical 

Research 

Laboratories, Inc. 

Report Status: 

Report Date: 

CRL Study Number: 

Client Study Number: 

CRL Protocol Number: 

Study Dates: 

Study Title: 

Test Material: 

Sponsor: 

Sponsor Representative: 

Investigator: 

APPROVAL SIGNATURES: 

Ahita Lee Cham, M.D. 

Dermatologist 

Final Report 

December 12, 2014 

CRL81314-2 

FRET 09-0536-02 

CL 1.0 2014 

October 27,2014- December 5, 2014 

Repeated Insult Patch Test (RIPT) -Shelanski Method 

FRET 09-0536-02 (2% in EtOH:DEP(1 :3)) 

International Flavors & Fragrances Inc. 

800 Rose Lane 

Union Beach, NJ 07735 

Paul Sterchele, PhD 

Senior Regulatory Toxicologist 

Global Regulatory Affairs 

Anita Lee Cham, M.D. 

Dermatologist 

Date 

371 Hoes Lane, Suite 100 • Piscataway, NJ 08854 • (732) 981-1616 • FAX (732) 981-0520 
Clinical 

Research 

Laboratories, Inc. 

····•· Go.od €iinic~I\Praetice·•·•·· 

.. · ... Quai · • ~$sltt~;c~ A:ijdit St~t~lllent · · 

Clinical Study Number: CRL81314-2 

Start Date: October 27, 2014 

Completion Date: December 5, 2014 

The clinical study listed above was conducted in accordance with Clinical Research 

Laboratories, Inc. Standard Operating Procedures, which incorporate the principles of 

Good Clinical Practice defined by applicable guidelines and regulations established by 

U.S. Regulatory Agencies. The conduct of the study was monitored for compliance, and 

the associated records, including source documents or raw data, were reviewed for 

documentation practices and accuracy by a Project Manager/Study Director and/or a 

Quality Assurance Representative. Standard Quality Assurance audit procedures for this 

---fmal report and study related documents were conducted. 

The Project Manager verifies that the clinical study listed above was executed according 

to the study protocol and all documentation contained in the study file accurately reflects 

the conduct of the study. 

1>--fi>---/t'/ 

"'Signature of Project Manager Date 

J)a_ . 1 J, 2 tf( 

Date 
Clinical 

Final Report 

Sponsor: Intematiotlal Flavors & Fragra11ces Inc. 

Study Number: CRL81314-2 

Page3ofl4 

Research 

Laboratories, Inc. 

FINAL REPORT 

Repeated Insult Patch Test (RIPD - Shelanski Method 

1.0 SUMMARY 

One hundred twelve subjects participated in evaluating the potential of FRET 09-

0536-02 (2% in EtOH:DEP(I :3)) to elicit dermal irritation and/or induce 

sensitization. The test material was applied under an occlusive patch to the upper 

back of each subject and was allowed to remain in direct skin contact for a period of 

24 hours. Patches were applied to the same site on Monday, Wednesday, and 

Friday for a total of 9 applications during the Induction Period. The sites were 

graded by a CRL technician for dermal irritation· 24 hours after removal of the 

patches by the subjects on Tuesday· and Thursday and 48 hours after removal of the 

patches on Saturday 

Following approximately a 2-week rest period, challenge patches were applied to 

previously untreated test sites on the back. After 24 hours, the patches were 

removed by a CRL technician and the test sites were evaluated for dermal reactions. 

The test sites were re-evaluated at 48 and 72 hours. Subjects exhibiting reactions 

during the Challenge Phase of the study may have been asked to retum for a 96-

hmrrreading. 

One hundred subjects completed the study. The test material identified as FRET 

09-0536-02 (2% in EtOH:DEP(l :3)) did not demonstrate a potential for eliciting 

dermal irritation or sensitization under the following test conditions: 0.2ml of the 

test material applied to a 3.63 cm

2 occlusive patch. 

2.0 OBJECTIVE 

The objective of this study was to determine the dermal irritation and sensitization 

potential of a test material. 

3.0 INVESTIGATOR/INVESTIGATIVE SITE 

Anita Lee Cham, M.D. 

Dermatologist 

Clinical Research Laboratories, Inc. 

3 71 Hoes Lane, Suite 1 00 

Piscataway, New Jersey 08854 

732-981-1616 

4.0 SPONSOR REPRESENTATIVE/SPONSOR 

Paul Sterchele, PHD 

Senior Regulatory Toxicologist 

Global Regulatory Affairs 

International Flavors & Fragrances Inc. 

800 Rose Lane 

Union Beach, NJ 07735 
Fi11a/ Report 

Clinical Sponsur: Intemational Flavors & Fragram:es Inc. 

Study Number: CRLS/314-2 

Research 

Laboratories, Inc. 

5.0 TEST MATERIAL 

Page4of/4 

The following test material was provided by International Flavors & Fragrances Inc. 

and was received by Clinical Research Laboratories, Inc. on October 13, 2014. 

Test Material Test Condition Patch Type 

FRET 09-0536-02 

0.2 ml of the test material was applied to a 

3.63cm2 patch. The test material was applied to 

(2%in the patch as received and allowed to evaporate Occlusive* 

EtOH:DEP(1 :3)) for at least 30 minutes, but no longer than 90 

minutes, prior to patch application. 

The test material was coded with the following CRL identification number: 

CRL81314-2 

6.0 STUDYDATES 

This study was initiated on October 27, 2014 and was completed on December 5, 2014. 

7.0 PANEL SELECTION 

Each subject was assigned a permanent CRL identification number. All subjects 

signed an Informed Consent Form in compliance with 21 CFR Part 50: "Protection 

of Human Subjects" and a IDP AA Authorization Form in compliance with 45 CFR 

Parts 160 and 164. All subjects completed a Subject Profile/Medical History Form 

provided by Clinical Research Laboratories, Inc. prior to the study (Subject 

Demographics - Appendix I). Subjects who met the following Inclusion Criteria 

and none of the Exclusion Criteria were impaneled: 

7.1. INCLUSION CRITERIA 

a. Subject is male or female between the ages of 18 and 70 years; 

b. Subjects with no visible or known pre-existing skin diseases that might be 

confused with a skin reaction from the test material, or which may be reasonably 

expected to affect the outcome of the study. This includes subjects with 

psoriasis or active eczema, even if currently controlled through medication; 

c. Subjects who do not report a history of acute or chronic dermatologic, medical, 

or physical conditions that could interfere with dermal scoring; 

d. Subject agrees to avoid exposure of the test sites to the sun and to refrain from 

visits to tanning salons during the course of this study; 

e. Subject agrees to refrain from getting patches wet during the course of the study; 

*Occlusive Strip with Flexcon® (Strukmyer LLC, Mesquite,TX or equivalent) 
Clinical 

Research 

Laboratories, Inc. 

7.0 PANEL SELECTION (Continued) 

7.1 INCLUSION CRITERIA (CONTINUED) 

F1nal Report 

Sponsor: International Flavors & Fragr01tces Inc. 

Study Number: CRLS/3/4-2 

Page5of14 

f. Subject has signed an Informed Consent in conformance with 21CFR Part 50: 

"Protection of Human Subjects;" 

g. Subject has completed a HIP AA Authorization Form in conformance with 45CFR 

Parts 160 and 164; 

h. Subject is in generally good health and has a current Subject Profile/Medical 

History on file; 

i. Subject is dependable and able to follow directions as outlined in the protocol. 

7.2. EXCLUSION CRITERIA 

a. Subject is pregnant, nursing, or planning to become pregnant; 

b. Subject is currently using any systemic or topical corticosteroids, antiinflammatory drugs, or antihistamines on a regular basis; 

c. Subject reports allergies to cosmetics, toiletries, or personal care products; 

d. Subject exhibits any skin disorders, sunburn, scars, excessive tattoos, etc. in the 

test area; 

e. Subject has scheduled, or is planning to undergo, any medical or surgical 

procedures during the 6 week course of the study. 

f. Subjects who have reacted to an IFF test material within the past year. 

8.0 TEST METHOD SUMMARY 

This study was conducted using a modified Shelanski - Shelanski human patch test 

method*. Prior to the application of the patch, the test area was wiped with 70% 

isopropyl alcohol and allowed to dry. The test material, which was prepared as 

described in the Test Material section of the report, was. applied to the upper back 

(between the scapulae) and was allowed to remain in direct skin contact for a period 

of24 hours. 

Patches were applied to the same site on Monday, Wednesday, and Friday for a total 

of 9 applications during the Induction Period. This schedule may have been 

modified to allow for missed visits or holidays. If a subject was unable to report on 

an assigned test date, the test material was applied on 2 consecutive days during the 

Induction Phase and/or a makeup day was added at the end of the Induction Phase. 

*H.A. Shelanski and M.V. Shelanski, Proc. Sci. Sect. Toilet Goods Assoc. 19:46, 1953. 
Clinical 

Final Report 

Sponsor: International Flavors & Fragrallces Inc. 

Study Number: CRL81314-2 

Poge6 of/4 

Research 

Laboratories, Inc. 

8.0 TEST METHOD SUMMARY (Continued) 

The sites were graded by a CRL technician for dermal irritation 24 hours after 

removal of the patches by the subjects on Tuesday and Thursday and 48 hours after 

removal of the patches on Saturday, unless the patching schedule was altered as 

described above. 

The sites were graded according to the following scoring system: 

Dermal Scoring Scale 

0 No visible skin reaction 

± Barely perceptible erythema 

1 + Mild erythema 

2+ Well defined erythema 

3+ Severe erythema and edema 

4+ Erythema and edema with vesiculation 

If a "2+" reaction or greater occurred, the test material was applied to an adjacent 

virgin site. If a "2+" reaction or greater occurred on the new site, the subject may 

not have been patched again during the Induction Phase but may have been 

challenged on the appropriate day of the study. At the discretion of the Study 

Director, patch sites with scores less than a "2+'' may have been changed. 

Following approximately a 2-week rest period, the challenge patches were applied 

to previously untreated test sites on the back. After 24 hours, the patches were 

removed by a CRL technician and the test sites were evaluated for dermal reactions. 

The test sites were re-evaluated at 48 and 72 hours. Subjects exhibiting reactions 

during the Challenge Phase of the study may have been asked to return for a 96-

hour reading. 

9.0 RESULTS 

This study was initiated with 112 subjects. Twelve subjects discontinued study 

participation for reasons unrelated to the test material. A total of 100 subjects 

completed the study. 

Individual dermal scores recorded during the Induction and Challenge Phases 

appear in Table I. 

10.0 ADVERSE EVENTS 

No adverse events were reported during the study. 
Clinical 

Research 

Laboratories, Inc. 

11.0 CONCLUSION 

Fi1ral Report 

Sponsor: lntemational Flavors&. Fragrtmces Inc. 

Shtdy Number: CRLB/314~2 

Page 7ofl4 

Based on the test population of 100 subjects and under the conditions of this study, 

the test material identified as FRET 09-0536-02 (2% in EtOH:DEP(l :3)) did not 

demonstrate a potential for eliciting dermal irritation or sensitization under the 

following test conditions: 0.2ml of the test material applied to a 3.63 cm2 occlusive 

patch. 

12.0 RETENTION 

Test materials and all original forms of this study will be retained by Clinical 

Research Laboratories, Inc. as specified in CRL Standard Operating Procedures 

30.6 and 30.6C, unless designated otherwise by the Sponsor. 
Clinical 

Research 

Laboratories, Inc. 

TABLE I 

Summary of Dermal Scores 

Final Report 

Sponsor: International Flavors & FragrmJces Inc. 

Study Number: CRL81314~2 

PageS of/4 

·.,· ·•·•····· j '['~t.Ma.terialt I FRET 09-0536-02 (2% in EtOH:DEP(1:3)) 

. s~~j;cf . 

•.. ·· •.. : Jn.d.uctiori .S¢~tllS · · . · Chall~nge Scores . . · .. . . .. 

1."" ~ 

... 3······· 'il . ... CC ~ 

~X . : . I 8 · .. ·u ..• 48' .7Z • Njiij.~er 1 .. 2. ·. 5 . . .. 7. 9 1: ......... Ii:oui Ii:o)lr Hour 

1 0 0 0 0 0 0 0 0 0 0 0 0 

2 0 0 0 0 0 0 0 0 0 0 0 0 

3 0 0 0 0 0 0 0 0 0 0 0 0 

4 0 0 0 0 0 0 0 0 0 0 0 0 

5 0 0 0 0 0 0 0 0 0 0 0 0 

6 0 0 0 0 0 0 0 0 0 0 0 0 

7 0 0 0 0 0 0 0 0 0 0 0 0 

8 0 0 0 0 0 0 0 0 0 0 0 0 

9 0 0 0 0 0 0 0 0 0 0 0 0 

10 0 0 0 0 0 0 0 0 0 0 0 0 

11 0 0 0 0 0 0 0 0 0 0 0 0 

12 0 0 0 I·· 0 0 0 0 0 0 0 0 0 

13 0 0 0 0 0 0 0 0 0 0 0 0 

14 0 0 0 0 0 0 0 0 0 0 0 0 

15 0 0 0 0 0 0 0 0 0 0 0 0 

16 0 0 0 0 0 0 0 0 0 0 0 0 

17 0 0 0 0 0 0 0 0 0 0 0 0 

18 0 0 0 0 0 0 0 0 0 0 0 0 

19 0 0 0 0 0 0 0 0 0 0 0 0 

20 0 0 0 0 0 0 0 0 0 0 0 0 

21 0 0 0 0 0 0 0 0 0 0 0 0 

22 0 0 0 0 0 0 0 0 0 0 0 0 

23 0 0 0 0 0 0 0 0 0 0 0 0 

24 0 0 0 0 0 0 0 0 0 0 0 0 

25 0 0 0 0 0 0 0 0 0 0 0 0 
... 

Clinical 

Research 

Laboratories, Inc. 

TABLE I 

(Continued) 

Summary of Dermal Scores 

Final Report 

Sponsor: Jnternatiollal Flavors & Fragrances Im:. 

Study Number: CRL81314-2 

Page 9 of/4 

·· ·· •. · ·· • ••• T!\SfMatelia.i: I FRET 09-0536-02 (2% in EtOH:DEP(l :3)) 

Su!>.Jed · ··. . . .. ··. · ~!i.u!!liol1 Si:t)t¢$ ! ·•··. •·• •... · • • •••••• . • CbAUe!!g¢ Scores 

Nlil11!>er · .1 l 3 •..• 4. .•. · ···••s r:···~ . ····~ . 8 .•· .. • 9• J ·· .2~L •48. 72 .. 

I i!' · • H:ilur. Hour :Hour .. 

26 0 0 0 0 0 0 0 0 0 0 0 0 

27 0 0 0 0 0 0 0 0 0 0 0 0 

28 Discontinued 

29 0 0 0 0 0 0 0 0 0 0 0 0 

30 0 0 0 0 0 0 0 0 0 0 0 0 

31 0 0 0 0 0 0 0 Discontinued 

32 0 0 0 0 0 0 0 0 0 0 0 0 

33 0 0 0 0 0 0 0 0 0 0 0 0 

34 0 0 0 0 0 0 0 0 0 0 0 0 

35 0 0 0 0 0 0 0 0 0 0 0 0 

36 0 0 0 0 0 0 0 0 0 0 0 0 

37 0 0 0 0 0 0 Discontinued 

38 0 0 0 0 0 0 0 0 0 0 0 0 

39 0 0 0 0 0 0 0 0 0 0 0 0 

40 0 0 0 0 0 0 0 0 0 0 0 0 

41 0 0 0 0 0 0 0 0 0 0 0 0 

42 0 0 0 0 0 0 0 0 0 0 0 0 

43 0 0 0 0 0 0 0 0 0 0 0 0 

44 0 0 0 0 0 0 0 0 0 0 0 0 

45 0 0 0 0 0 0 Discontinued 

46 0 0 0 0 0 0 0 0 0 0 0 0 

47 0 0 0 0 0 0 0 0 0 0 0 0 

48 0 0 0 0 0 0 0 0 0 0 0 0 

49 0 0 0 0 0 0 0 0 OHr 0 0 0 

50 0 0 0 0 0 0 0 0 0 0 0 0 

Hr- Hyperpigmentation 
Clinical 

Research 

Laboratories, Inc. 

TABLE I 

(Continued) 

Summary of Dermal Scores 

Fi1Ja/ Report 

Sponsor: lntemational Flavors & FragraJtces Inc. 

StudyNumber: CRLB/314·2 

Poge/Oof/4 

: j f¢&ti\tl:jj,'tetiai:·I FRET 09-0536-02 (2% in EtOH:DEP(I :3)) 

···-- : ....... ,:. 

. ' ' - : ..... ·.•··· u :•·•··-·· : -~~d~~~~~:ii~~r¢~·) • , ......... .. c~!ll,~~g¢ s~~J:t,!l .. , S:~J>ject. 

· ~~ii{bel' , .. 1.- A f it lr!-# 1-)P······ ······-···~:-.•. i• ·-r:- >/8 9 ••.•••. . 24 .. 48 71, --- : .. · .. · .... Iillur 'il9i!t . . llour : ,. ''· 

51 0 0 0 0 0 0 0 0 0 0 0 0 

52 0 0 0 0 0 0 0 0 0 0 0 0 

53 0 0 0 0 0 0 0 0 0 0 0 0 

54 0 0 0 0 0 0 0 0 0 0 0 0 

55 0 0 0 0 0 0 0 0 0 0 0 0 

56 0 0 0 0 0 0 0 0 0 0 0 0 

57 0 0 0 0 0 0 0 0 0 0 0 0 

58 0 0 0 0 0 0 0 0 0 0 0 0 

59 0 0 0 0 0 0 0 0 0 0 0 0 

60 0 0 0 0 0 0 0 0 0 0 0 0 

61 0 0 0 0 0 0 0 0 0 0 0 0 

62 0 0 0 0 0 0 0 0 0 0 0 0 

63 0 0 0 0 0 0 0 0 0 0 0 0 

64 0 0 0 0 0 0 0 0 0 0 0 0 

65 0 Discontinued 

66 0 0 0 0 0 0 0 0 0 0 0 0 

67 0 0 0 0 0 0 0 0 0 0 0 0 

68 0 0 0 0 0 0 0 0 0 0 0 0 

69 0 0 0 0 0 0 0 0 0 0 0 0 

70 0 0 0 0 0 0 0 0 0 0 0 0 

71 0 0 0 0 0 0 0 0 0 0 0 0 

72 0 0 0 Discontinued 

73 0 0 0 0 0 0 0 0 0 0 0 0 

74 0 0 0 0 0 0 0 0 0 0 0 0 

75 0 0 0 0 0 0 0 0 0 0 0 0 
Clinical 

Research 

Laboratories, Inc. 

TABLE I 

(Continued) 

Summary of Dermal Scores 

Fi11af Report 

Sponsor: International Flavors & Fragra1Jces /1Jc. 

Study N11mber: CRL81314-2 

Page 11 af/4 

··•·•·r . ~$t~terlal! I FRET 09-0536-02 (2% in EtOH:DEP(1:3)) 

... .. • 

···•. ·•••· • ··•.· •·•·•··· .. Il)"duc;ti.!ln ~~~~.e~ < · ···· · Cbaiie:i\ge $.e~l'~ ·•sll~J.~t ... .. . .. ,. ····· ..... 

·•· ······~········ 1:. : 4 •.• I 7. 1·'9< .z<~ '48 •• 72 ·.:~~m.~~[ I l z • 5 

•·••·• ,6 · ... ' I I! ll~(ii •. i!i:lillr lJQi!~< 

76 0 0 0 0 0 0 0 0 0 0 0 0 

77 0 0 0 0 0 0 0 0 0 0 0 0 

78 0 Discontinued 

79 0 0 0 0 0 0 0 0 0 0 0 0 

80 0 0 0 0 0 0 0 0 0 0 0 0 

81 0 0 0 0 0 0 0 0 0 0 0 0 

82 0 0 0 0 0 0 0 0 0 0 0 0 

83 0 0 0 0 0 0 0 0 0 0 0 0 

84 0 0 0 0 0 Discontinued 

85 0 0 0 0 0 0 I 0 0 I 0 II 0 X I 0* 

86 Discontinued ' 

87 0 0 0 0 0 0 0 0 0 0 0 0 

88 0 0 0 0 0 0 0 0 0 0 0 0 

89 0 0 0 0 0 0 0 0 0 0 0 0 

90 0 0 0 0 0 Discontinued 

91 0 0 0 0 0 0 0 0 0 0 0 0 

92 0 0 0 0 0 0 0 0 0 0 0 0 

93 0 0 0 0 0 0 0 0 0 0 0 0 

94 0 0 0 0 0 0 0 Discontinued 

95 0 0 0 0 0 0 0 0 0 0 0 0 

96 0 0 0 0 0 0 0 0 X Discontinued 

97 0 0 0 0 0 0 0 0 0 0 0 0 

98 0 0 0 0 0 0 0 0 0 0 0 0 

99 0 0 0 0 0 0 0 0 0 0 0 0 

100 0 0 0 0 0 0 0 0 0 0 ± ± 

X~ Subject Absent 

*No reaction was observed at the 96 hour evaluation 
Clinical 

Research 

Laboratories, Inc. 

TABLE I 

(Continued) 

Summary of Dermal Scores 

Final Report 

Sponsor: lntemational Flavors & Fragrances Inc. 

St11dy N11mber: CRL81314-2 

Page/2of/4 

. T~t'l\iatel'ial: I FRET 09-0536-02 (2% in EtOH:DEP(1:3)) 

· · · ·· •·• · • ·· · · .. · · ·· ·. . .• ·: ID:duetillnSc<!res .. · •• ·· 

•.- .•... Ns •. .. -~_-·_·. b.•.-.~·.·.•_•.·_J_._ .. eb.·_._·· .. c··.· •. ·~_··.t.~.·· ••.•.. • •.• _.·.···· ·. •...• · _· ..•_._._I· ••.. •.··. ... · _.· . . . . . . .. . . 

......... "'. Z13J4 

........ .. d~ijJ!JQ:ge Scor¢s · • 

.Z4 :41! .. 72 .. 

9 .. . Hour lioiir · .. Uti11r 

. . 

.. . . : .. 'l . 5 .... . ·: 8 .. . 6 

101 0 0 0 0 0 0 0 0 0 0 0 0 

W2 0 0 0 0 0 0 0 0 0 0 0 0 

W3 0 0 0 0 0 0 0 0 0 0 0 0 

104 0 0 0 0 0 0 0 0 0 0 0 0 

1~ 0 0 0 0 0 0 0 0 0 0 0 0 

106 0 0 0 0 0 0 0 0 0 0 0 0 

107 0 0 0 0 0 0 0 0 0 0 0 0 

108 0 0 0 0 0 0 0 0 0 0 0 0 

109 0 0 0 0 0 0 0 0 0 0 0 0 

110 0 0 0 0 0 0 0 0 0 0 0 0 

111 0 0· 0 0 0 0 0 0 0 0 0 0 

112 0 0 0 0 0 0 0 0 0 0 0 0 
Sullj~\!t 

Nwnb.er 

1 

2 

3 

4 

5 

6 

7 

8 

9 

10 

11 

12 

13 

14 

15 

16 

17 

18 

19 

20 

21 

22 

23 

24 

25 

26 

27 

28 

Clinical 

Research 

Laboratories, Inc. 

Appendix I 

Subject Demographics 

•subject· ·cro,. 

·····~~~···· ·$¢~· • Iuitillls · J»tf swJ~:iit. 

Nlil#J)e.f · 

DN 33175 34 F 29 

MC 02025 33 F 30 

BW 17003 64 F 31 

JB 14759 63 F 32 

JD 11122 53 F 33 

MS 13309 35 F 34 

DB 32989 56 F 35 

KT 31548 64 F 36 

ER 30633 56 F 37 

RV 08103 37 F 38 

BS 28576 61 F 39 

KW 30192 64 F 40 

SL 18114 38 F 41 

DL 25050 43 F 42 

TL 33407 42 F 43 

RP 31532 63 M 44 

FP 24056 59 F 45 

GK 18831 29 M 46 

AE 29803 31 M 47 

MC 28585 38 F 48 

JG 27625 63 F 49 

MB 18220 67 F 50 

DG 01828 56 F 51 

AG 32545 57 F 52 

WB 30469 64 M 53 

ss 27553 57 F 54 

AA 32652 60 M 55 

RT 31341 51 F 56 

Filtal Repot1 

Spo11sor: llrtemational Flavors & FragraiJCes Inc. 

Study Number: CRL81314~2 

Page13ofU 

$u'I:J]~~t CRb .Ag¢• Sex ~D.!tj~~ ·• Iri# 

BB 01668 51 F 

TA 33389 46 F 

JB 25556 38 M 

PR 05291 52 F 

CM 00741 69 F 

JG 24987 54 M 

JA 05348 65 F 

ED 20237 55 F 

DM 15909 59 F 

DM 27962 57 F 

DT 32525 66 F 

CR 29212 46 F I 

JS 30187 53 F 

AB 23147 49 F 

Nl 33422 20 F 

DL 09278 54 F 

MO 33415 55 F 

IN 03306 69 F 

DR 31032 52 F 

AC 33413 22 F 

CN 27549 52 F 

BW 27548 67 F 

DP 32402 63 F 

CA 33435 55 M 

MR 31934 18 M 

MV 02437 68 F 

uw 33434 50 F 

CM 19646 56 F 
:SJI~j¢~tH 

:Nii&:b~r 

57 

58 

59 

60 

61 

62 

63 

64 

65 

66 

................... 67 

68 

69 

70 

71 

72 

73 

74 

75 

76 

77 

78 

79 

80 

81 

82 

83 

84 

Clinical 

Research 

Laboratories, Inc. 

{S*bj¢¢tT dRI.:. 

WtiiilS .•.• ·lD# 

GK 03981 

NC 10624 

MT 30825 

FT 28815 

AD 32492 

NC 33362 

NP 30154 

ER 33363 

SH 33411 

AS 33436 

LR 33408 

AM 32178 

CB 33196 

AC 19727 

PT 31460 

CR 09622 

JR 29685 

CB 24697 

GF 23083 

JB 29335 

ss 06517 

WM 33214 

HG 33133 

JH 19225 

TC 29284 

SK 18539 

LJ 33022 

LN 24351 

Appendix I 

Subject Demographics 

(Continued) 

I Age Sei ........... • 

IJ.Sill>'ect· ···.:.~'\.':'' 

63 F 85 

36 F 86 

24 F 87 

45 F 88 

54 F 89 

51 F 90 

28 M 91 

44 M 92 

41 F 93 

18 M 94 

34 F. 95 

38 F 96 

54 F 97 

29 F 98 

54 F 99 

56 F 100 

67 F 101 

62 F 102 

51 F 103 

58 F 104 

59 F 105 

37 M 106 

56 M 107 

50 M 108 

34 F 109 

62 F 110 

34 M 111 

48 F 112 

Final Report 

Sponsor: International Flavors & Fragrances I11c. 

Study Number: CRL81314v2 

Page 14ofl4 

~ii~J¢1\t . dRI..< 

tnitiau lD#·· Age. Sex 

PN 03277 57 F 

ER 33438 22 M 

LJ 28423 45 F 

DC 20624 61 F 

RC 31248 21 M 

JL 31000 49 F 

PS 31629 56 F 

MP 33431 20 F 

cw 16399 54 F 

JW 32123 39 F 

KH 33439 25 M 

BT 33424 42 M 

JP 22148 39 F 

RE 26689 42 M 

AA 29940 20 F 

DW 20399 54 F 

RJ 26063 52 F 

NF 14449 58 F 

BC 30844 23 F 

AS 02343 65 F 

TM 30142 46 F 

JG 16720 29 F 

JN 30414 32 F 

JS 24960 53 F 

ST 27390 56 F 

KB 32105 41 F 

DL 27410 53 F 

AM 13130 48 F 
HRIPT FRET 09-0536 

TEST SAMPLE 

Sample preparation: R&D (Gary Mertz) 

Request date: September 17, 2014 

Test Chemical: FRET 09-0536 

Test Article FRET 09-0536-01, 2% w/w in Ethanol:DEP [25:75] 

8 

98 

294 

400 

g 

g 

g 

g 

FRET 09-0536 

Ethanol 

Diethyl Phthalate (043615) 

Total 

Final FRET 08-0338 Concentration= 8/400 (2% w/w) 

Test Article FRET 09-0536-02, 2% w/w in Ethanol:DEP [25:751 

8 

98 

294 

400 

g 

g 

g 

g 

Distilled water 

Ethanol 

Diethyl Phthalate (043615) 

Total 

··· ·· Final Distilled Water Concentration= 8/400 (2% w/w) ···································· 

PFS