Document 8GbXx68Dawdb8Er8k9BXn3Z

AR226-3000 Study Title 100-Person Human Patch Test vith H-203B5 (Control Item) and H-20386 (Test Item) Laboratory Project ID Haskell Laboratory Report No. 792-93 Study Completed On 25 February 1994 Contracting Laboratory Biosearch, Incorporated 3408-50 B Street Philadelphia, Pennsylvania 19134 Author Armand Affrioe for Haskell E. I. du Font de Nemours and Company Laboratory for Toxicology and Industrial Elkton Road, P. 0. Box 50 Newark, Delaware 19714 Medicine Study Monitor John R. Bamberger Medical Research No. Company Sanitized. Does nol contain TSCA GBS Page 1 of 25 Material Tested; Physical Fora 8 Synonyms i Coepoaitions GEHERAL INFORMATION Qontrol H^frUl DuPont BIG 79293 Material Tested; Physical Fora; Synonyms; Composition; Sompany SanStfzed. D&ss nol1 eontein TSCA GB9 2 - GENERAL INFORMATION (CONT.) DuPont BLO 792-93 Stability; In the absence of visible evidence to the contrary, the teat Materials vere assu--d to be stable under the conditions of administration. Sponsor; Study Initiated - Completed; In-Life Phase Initiated - Completed; DuPont Fibers B. I. du Font de Nenours and Coapany VilBlngton, Delaware 10 January 1994 - 25 February 1994 10 January 1994 - 17 February 1994 3 - - eed. Does not contain TSCA-es? DUPONT CENTRAL RESEARCH AND DEVELOPMENT HASKELL LABORATORY FOR TOXICOLOGY AND INDUSTRIAL MEDICINE DuPont HLO 792-93 Joyce M. Haterniak DuPont Fibers Chambers Works 25 February 1994 100-Person Huoan Patch Test with H-20385 (Control Item) and H-20386 (Test If) Attached is a report from Biosearch, Inc. (Project No. 93-7949H). in the report are patch test methods, results, and conclusions. Included The purpose of this study was to determine the potential of H-20385 (Control Item) and H-20386 (Test Item) to cause delayed contact hypersensitlvity in humans. During the induction and challenge phases of this study, H-20385 (Control Item) and H-20386 (Test Itea) produced no adverse skin responses in 100Z and 1002, respectively, of those subjects vho were active participants. Based upon the effects observed with the test oaterials placed repeatedly on the skin during both the Induction and challenge phases, neither H-20385 (Control Item) nor H-20386 (Test Item) are considered sensitizing agents under the conditions that prevailed in this study. ^fi.M^y. John R. Baoberger, B.S. Toxicologist 4 - DuPont HLO 792-93 BIOSEARCH INCORPORATED P.O. Box 8598, Philadelphia, Pennsylvania 19101 Telephone: (215) 7394499 Pax: (215) 423-9210 Project Number: TMHng Fan-lity Sponsor: TeBtArBcleTeat Article Description: Tent Article Received: Study In.tiahxjPate of Report: leak Object of Test: Reference: Method of Teat; 93-7949H Biosearch Incorporated 3408.50 uy Street Philadelphia, PA 19134 E.I. Du Pbnt De Nemouxs & Company P.O. Box 50, EBcton Road Newark, DE 19714 ?20385 12/14/93 01/10/94 Study Completed: 02/17/94 02/25/94 Modified Draize Repeated Insult Patch Test Study in Human Volunteens. To determine the irritating, fatiguing and sensitizing properties of the test article. The method employed in carrying out this test was similar to that described in "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" by J.H. Draize and published by die Association of Food and Drug Officials of the United States. Test Panel: The test involved the application of the test article to the upper arms of a group of 120 volunteer panelists. The panelists involved in this study ranged from 18 to 55 years of age. One hundred and ten panelists completed the study (see Panelist List, Appendix I). These panelists were all determined to be in good general health and free of any visible skin disease or anomaly in the area to be patched. Each panelist was required to read, understand and sign an informed consent statement. Company Sanitized. Does noli contain TSCA GBS Project Number: 93-7949H DuPont HLO 792-93 Page 2 of 9 E.I. Du Font De Nemoure & Company H-20385 Modified Draize Repeated Insult Patch Test Study in Human Volunteers Method of Teah (continued) Patch Preparation: The teat article was tested as supplied. A portion of test article, approximately one inch square, was applied to the appropriate skin site and covered with 2" Dermicel hypoallergenic cloth tape Qohnson & Johnson, New Brunswick, N) 08903). Induction Phase: The patch was applied to its designated contact site on the upper arm, and remained in place for 24 hours. At the end of this period, the patch was removed and the site was examined for any dermal response. The panelists were then rested for a 24-hour period after which the skin site was again examined. A patch was then applied to the same site as previously used. The second opplication was identical to the first and remained in place 24 hours. This procedure was repeated on Mondays, Wednesdays and Fridays until a series of nine applications had been made. Patch applications made on Friday were removed by the panelist on Saturday. The panelists examined the site for any dermal response and reported their observations prior to the next application. The same site continued to be used throughout the study. In the event when one induction patch application was missed, the panelist was allowed to make it up at the end of the induction patch period. This was done on the Monday following the last scheduled induction patch application. Severe ice and snow storms in January made travel to the laboratory impossible for some of the panelists on several test days. Adjustments in the test schedule for individual panelists are shown in Table 1. Challenge Phase: After the 9th application, a rest period of approximately 2 weeks elapsed after which a challenge application was applied in the same manner and to the same site as described above. A duplicate challenge application was also applied in the same manner to a virgin site (previously untreated) on the other arm. The challenge application was removed after 24 hours and the sites were examined and graded for signs of irritation or sensitization. A follow-up examination was conducted at 48 hours after the challenge application. Grading Stale: The grading scale used throughout both the induction and challenge phases is shown in Appendix II. Results: Individual panelist data are presented in Table 1. A summary of the data is presented in Table 2. Conclusion: From the results obtained with this test panel, the test article is most likely not a primary skin irritant. The test article is most likely not a fatiguing agent. The test article is most likely not a sensitizing agent. Company ganiffeetf. Does not eontafn TSCA QW HIOSliARCH, INCORPORATKD - P.O. BOX 8198 - PHILADELPHIA, PENNSYLVANIA 19101 - 6 - Pmj^t Nnn^- 93-7949H E.I. Du Pon' De Nemoun &ac Coftipany H-'20385 DuPont HLO 792-93 Page 3 of 9 Modified Draize Repeated Insult: Patch Teat Study in Human Volunteers Signaturea: Submitted by,Bioeearch,Incorporated: ^Da6 W y^/9/ Date ^ 1 ^ Date Approved by: ^esE.'I^l/Sc.D. Vice Presiden:, Laboratory Operations & Regulatory Affairs Kari L. Gabriel, V.M.D., Ph.D. President 4^ /fr _ D5a^te S^/^ z-zr^Y Date ompany Saniirzed. Does notcontafn TSCAeE9 BIOSBARCH, INCORPORATED P.O. BOX UW PH1LADBLPHIA, PENNSYLVANIA 19101 - 7 - Y.-.-" ffr?1ftgr HuntiH- 93-794911 B.I. Ou Pont D Nemours 6 Coenpany - H-20385, as supplied. Modified Draixe Repeated Insult Patch Teat Study in Human Volunteers Table l - Individual Panelist Data induction Phase Subject 1 24 48 00 2 24 48 C10 3(S) 24 48 0 () 24 48 00 567 24 48 - 0 24 48 00 24 4B 00 8 24 48 0 9 24 48 0 oa ' 0 0 3 V as ^ W 1 K' <B n. 0 0 (B W 3 0 W 0 0 1 9 V> 0 B 9 10 11 12 13 14 15 1C 17 r 19 20 21 22 23 J4 25 (S) . 24 48 (a) . 0 0 0C) C} 0 C1 0 0 - 0 0 00 00 00 6) 0 0 . D ,0 0 0 D D .SL 0. Jtt B 0 1 C 1 0 1 C 1 0 ) t ) D1C0 0 C 1 1 0 ( C 1 C 1 C ) 0 0 00 00 00 C) 0 ( 00 00 00 C1 0 (1 00 00 00 C) 0 0 0 ( 00 C) 0 ( 00 00 o(a) o o 0 ( 00 C1 0 00 00 00 9 0 0 0 (B 0 0 0 C1 0 < 00 00 0(a) 0 0 0 ( - 0 0DO0 (1 0 0 (0 t 1 C 0000 0 0 0000 C 9 0 0 (1 0 ( a 0o0o 0 10 00 0 0 0000 ( (0 0 (D 0 (9 (DO D0 0D D00D 00 D J 00 t 9 0 00 0 (9 0 (0 0000 - 0 00 - 0 00 0000 0000 ( 9 ( 9 0 0 0 0 0000 0000 - 0 00 0000 0000 ( 9 00 0 0 0000 0000 0000 (a) 0000 0000 0000 0000 0 0 0 0 0 (0 0 Day of severe ice and snow storms. Reading 24 hours after application. Reading 48 hours after previous application but just before next application. Hissed reading. Patch applied l.day late. Discontinued for personal reasons. BIOSBAROT, INCORPORATE} - P.O. BOX 8598 - PHXXADXLPHZA, PBWSTLVMtIA 19101 Orig S 2 (215) 73 PrOlQCt HUBbflJ: 93-7949H B.I. Du Pent De Neiaours 6 Coiopany - H-203B5, B supplied. Modified Oraize Repeated Inault Patch Test Study in Human Volunfceera Subject '*-' 26 27 U. 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 () 24 48 * * ^ D - Table l - Individual Paneliat Data (continued) '1 2^ 48 2* 24 48 3<i-i) 24 48 4-i(-) 24 48 Induction Phae - 5 24 48 6 24 48 7 244fi 8 al48. 9 24 48 l0* 3148. Orig 2 00-o,^.--^-fHf^o^----^o.^^-^00-00^-00 0000 00 0000 0000 ..0- o .... a 0 DODD ^o------t^- 00 00 00 00 0 000000 0(a0)-0 ---000 000 21000000 0000000000000000000000000000000000 00000000000000000000 000000000000 00000000 (a)0000000-00000000 0000000000000000 0000 00 0 0 - 0 0(a) 0 C 0(a) 0 0) 0 0 0 0 " * 0 0 (a) - 0 0 0 - 0(a) 0(a) 0 Ola) 0 0 1 - C ) 0 0) 0 0) 0 C1 0 C 0 - 0 - 0 -* 0 - 0 0(a) 0 - (a) 0 C1 0 ) 0 C1 0 C1 0 (1 0 (l - 0 CO - 0 - 0 0 0 0 D 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Of1 0 (a 0 (i 0 (D 0 (D D IB t9 0 (1 I1 ( C1 (a c) ( c (1 C> . (9 C8 0 C1 (D C1 (& ( DO ( (0 0 0 Ot 0 (0 0 0 0 <0 C 1 < D ( 1 ( 0 ( 1 ( D 0 0 ( D 0 0 0 ( D 0 0 ( 0 0 0 * - . - - - Day of aevere ice and now atorma. Reading 24 hour* after application. Reading 48 houn after previou* application but juat before next application. HiBaed reading. Read at 72 hour*. PaAnfel l4i1a^t mk4i--a--a--e-d^l .kt.ht^--e a--c--h--e-d--u---le^d-^ p--a^tch application for peraonal reaaona. Paneliat waa patched on th next acheduled application day, and the patch aerie extended until 9 induction applieationa <*e Make-up patch application, (a) P afceh applied l day late. Diacontinued for peraonal reaaona. BI08BARCH, XNCORPORATBD - P.O. BOX 8598 - PHILADELPHIA. VaWSWWMSU. 19101 - (215) 73  1 0 i s - S9 ; i Oi s 3 ptS S3' <o P" 3 0 >0 w 3 0 18"<t or 5' -y( Project JSsatoat-- 93-7949H B.I. DU Font Dt Neroouf 6 Company - H-20385, as supplied. Modified Oraise Repeated Insult Patch Teat Study in Huaan Volunteera Table l - Individual Panel ict Oat* (cootiavd) Subject ffiaffir 51 sz" 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 () 24 48 * (a) - D 1 21-12 2 24 U 3() 21.U 4(1) 31 41 5 ^ 18 6 MJA 7 M 21U 9 10* M-il M It Orig S 2 00 0000 wo 00 -o" o 00 Ty-Tr 00 T~- -" 00 00 - fftaT 0' "o' 00 "o--o ~v~~vr v v o o D0 -0 -0 000 0000 0000 0000 0 - 00 00 0000 00 - 0 0000 0000 00 o - 0(a) 0 0 o o(a) - o 0oo0 0 o 0 0 0 0 - 0 - 0 0000 0000 0 0 0 0 0 0 () 00 - 0 0000 0000 0 00 0 0 0 0 0 0 0000 0000 00 00 0 0 0000 0000 0 0 0 0 0000 0000 0000 0000 0 0 0000 0 0 00 0 0000 0000 0000 0000 0 0 0000 0 0 0 0<a) 0000 0 0 O00D D00D 0 D 0000 0 0 00 00 0<a> - -< - o(a) 0 0 0 . CO 0 0 0 0 0 (b) 000-0 0000 0000 0 0 0 0 0 0000 0000 0 0 0 00 0000 0 0 0000 0000 (a) 0 0 00 0 00 00 (a)- 00 00 0 Day ot aevre ice and mow tonu. Reading 24 hcniri after application. Reading 48 hour* after previoua application but jiut before next application. Hiaaed reading. * Make-up patch application. Paneliat aired the cheduled patch application Co. pereonal reaaone. Paneliat waa patched on th next cheduled application day, and the patch aeriea extended until 9 induction applieateiooe wer Patch applied 1 day late. (b) Paneliat received l oake-up; technical error. Diacontinued for peraonal reaeona. ' BIOSEARCH, IHCORPORATBD - P.O. BOX B59B - PHILADKLPHIA. PBM8YLVMIA 19101 - (215) 73> <y Pro-iect Number: 93-7949H B.I. Du pont De Hemours 6 Company - H-20385, as supplied. Modified Oraize Repeated Inault Patch Test Study In Human Volunteer* Subject liyabcc ft 0 1 w 3 < U) a) S; N' & CT 0 CO VI 3 S. 8 i^ '--" ;^i ;;!- o G? 76 77 78 79 BO 81 82 83 84 85 6 87 8 " 90 9l 92 ,," 9* 9S 96 97 98 " 100 () - 24 . " ^ - o Table 1 - Individual Panelist Data (continued) 1 24 48 2 24 48 3(1) 24 48 4 (a) 24 48 Induction Phase 5 24 48 6 24 48 7 24 4B 8 24 48 9 24 48 X0* J448. Orig 2 -0 000 0000 00 00 0000 0000 00 - 0 -* 0 0(a) 0 0 - 0 0 000 0 a o o- A o o o o o---o-h^ "o i>- - -o v - - oo 0 0 0 0 00 00 00 00 00 0 0 0 0 0 00 00 00 00 0 0 0 0 0 00 00 00 0 0 0 0 0 0 0000000000 0 0 0 0 0(a) 00 0000 0 0 0 0 . 0 0 0 0 000000 0 o(a) 00 0o 0 -* o -* - 0 - o 0 0 0 0 0 0 0 0 0 0 0(a) 0(a) 0000 0000 0000' 0 0 0 0 o(a) 00 - o 0<a) o o - 0 oo 00 0 00 0 0 0 0 0o0o - o(a) - o 00 00 o0o0 o0o0 0 0 0 0 00 0000 0000 0000 0000 0000 0 0 0 0 0 0 0 0 0000 0000 0000 0000 0000 0 00 0 00 0 0 0(a) - 0 DD DO DO 0 0 DDOD 0000 0 0 0000 0000 0000 0000 00 00 0000 Day of ever ice and now forma. Reading 24 houri fter application. Reading 48 houra fter previous application but juat before next application. Hiaaed reading. Panaliat miaaed the acheduled patch next acheduled application day, and Hake-up patch application, Discontinued for peraonal reaaona. BZOSURCR, INCOKPORATBD - application for peraonal reaaona. Paneliat was patched on th the patch aeriea extended until 9 induction applicatioa* we (a) Patch applied l day late. * P.O. BOX 8598 - PHILADKLPHIA, SWHSWnWU, 19101 - (215) 73 Pro-lect Number: 93-7949H B.I. Du Font De ttemours 6 Company - H-20385. as supplied. Modified Draize Repeated Insult Patch Test Study in Human Volunteers Table 1 - Individual Panelist Data (continued) Subject PUfflffr 1 24 4B 2 24 48 3(B) 24 48 40 24 48 induction Phw 5 24 48 6 24 48 7 24 48 B 24 48 9 24 48 10* 3111 Origi S 24 101 102 103 104 105 106 l 107 108 M 109 1 110 111 112 113 1If 114 115 116 B) 117 'e; 118 M 119 &) 120 3 u-ir KT. N 0000 0000 0000 0000 (a) 0000 0 0 0 0 0 0 0 0 0 0 ^0-00 oCOo g0o0 o00o 00 00 a -a . o (a) 00 0 ft -9 ... 0 ..... ...-o - 0 00 0000 0000 DO 00 DO 00 00 0 0 0 0 0 0000 0000 0000 (a) 0000 0000 0 0 0 0 0 0 DO 00 OD 00 0000 0000 0000 0 0 D b 0 0 0000 0000 0000 0000 0 -* 00 - 0 0 0 0 0 0 0 --00 0000 0000 0000 0000 0 0 0 0 0 0 O00D0 -0 --00 0000 0000 0000 0 - 0 0 0 0 0 0 0 D 0000 0000 0000 0000 (a) 0000 0 0 D 0 0000000000000000000 0000 - 0 00 0 0 0(a) 0(a) 0000 0 - - - - 0 - 00 0000 0 0 CD P. (S) Day of severe ice and snow storms. 0 24 Reading 24 hours after application. 0 4B Reading 4B hours after previous application biut just before next application. 0 w Hissed reading. 3 * ^ Panelist Biased the scheduled patch application Cor personal reasons. Panelist was patched on the 2. next scheduled application day, and the patch series extended until 9 induction applications were 0 0 * Make-up patch application. 3 (a> - Patch applied 1 day late. i"<' n.) D Discontinued for personal reasons. BIOSEAHCH, IHCORPORATBD - P.O. BOX 8S9B - PHILADELPHIA. PIKHSYLVM1IA 19101 (215) 739 Pryl-nyt W^sr- 93-79*911 E.I. Du Font Oe Nenours & Conpany - H-203B5, a upplied. Modified Draise Repeated Insult Patch Test Study in Hunan Volunteer* Table 2 - Suonary of Oaf Total Sub-lecta; Qrade induction Phase 24 130 1 2 3 48 24 48 24 48 l2B 120120 120120 424 48 120120 524 48 120 120 6789 24 48 24 48 24_48, ^4 48 120 120 120 120 ^120 UO -X20-120- 10** 24 48 -IX -17 Ori ---- - 1 0 116 117 115 116 116 114 94 104 91 101 101 110 107 110 109 110 110 109 17 17 1 t I* 0000000000000000000000000000000000000000 '0 3* 00000000000000000000 00000000000000000000 4+ 20 31 10 30 10 0100 20 820 10 10 0 D 2 3 3 3 3 6 6 8 9 9 9 10 10 10 10 10 10 10 0 0 24 48 - D - Reading 24 hour* after application. Reading 48 hours after previoua application but just before next application. Niaaed reading. Discontinued for personal reasons. BIOSBARCH, INCORPORATE) - P.O. BOX 8598 PHILADKLPRIA. PBMMSYLVMIXA. 19101 - (215) 739 DuPont HLO 792-93 BIOSEAKCH INCORPORATED P.O. Box & 98, Philadelphia, Pennsylvania 19101 Telephone:(215)739^ I Fax:(215)423-9210 Project Nmnhey Testing PadHty C TWArtirfpTart Artipip 93-7949H Biogearch Incorporated 3408.50-r Street PhUadelp lia, PA 19134 E.I. Du P t De Nemoun & Company P.O. Box 50, Elkton Road Newark, )E 19714 H-20386 TertArtidR Receive: Study InitiatedPatent Riepait: Teat: Object of Test: Referenpe: Method of Teat- 12/14^93 OVKV94 02/25/94 Study Cmnpleted- 02/17/94 Modified ,'Draize Repeated Insult Patch Test Study in Human Volunteers. To determine the irritating, fatiguing and sensitizing properties of the test article. The metf od eemn ployed in carrying out this test was similar to that described in-"AAppraisal of the Safety of Chcemicals in Foods, Drugs and Coon letics" by J.H. Draize and published by me Association of Food and Drug Officials of me United States. Teat Pand; The test involved thi application of me test article to me upper arms of a group of 120 volunteer panelists. The panelists involved jin mis study ranged from 18 to 55 years of age. One hundred jandten panelists completed the study (see Panelist list, AppehdbJIE). These panelists were all determined to be in good general Uealth and free of any visible skin disease or anomaly in me area to be patched. Each panelist was required to read, understand and sign an informed consent statement. ^^^^^DoesnoEcon^Ko^^, 14 PMfert Number: 93-7949H DuPont HLO 792-93 P*y2of9 E.I. Du Font De Nemours ft CompAny - H-20386 Modified Draize Repeated Insult Patch Teat StudyIn Human Volunteers Method of Tent: (continued) EatldLElBMCiafln: The teat article WM tested as supplied. A portion of test airNaft. 'ajaproNi^^ ^^.^JIg^ square, was applied to die appropriatea dn'sHe'^c@we'B(i:N|l> 2" Dennicer hypoallergenic doth tape Oohnsor & Jormson, New Bnniswick, NJ 08903). Inductiirn Phase: The patch was applied to its designated contact site on the upper ai^/ and for 24 hours. At the end of this re^ periud, the i^^^^;;9^;1l^^^ dermal xespopM- 'Tbe^^^^p^^ after whi"ch: " '''|ld)ri.|lt|i^:a^^ the site was examined for any Own rested for a 24-hour period A patch was then applied to the same sl^ as previow^^^^l^ The second application was identical to tl ||i9t aiul^iQi^^ place 24 hours. This procedure ai^^ was repeatea on Mondays, Wednesdays and Fridays until a series of nine appucanomhss had ^een niad^ 1^ applications nude on Friday were removed 1^the panelist 0^ The panelists examined die site for any dd jernulresponse their observations prior to the next applica""f '^^IIie:.!)!^1:^^^^ to be used throughout flu* .. -.-- *^', - - ^ -, event when <me^|J^ patch application was missed, the panelist as aUowed to mi^B^li^ at die end of me induction patch period. This was done on tne^^^ following the last scheduled induction pal application. ^ Severe ice ard snow atonns in Jannary made travel to the laboratory impossible foi some of the pane^ several test days. Adjustments in me test schedule for individual panelists are shown in Table 1. ChaUfiDge^ase: After the 9m application, a rest period of a p p r o x i ~ m a ttee!l) ^ 2 weeks elapsed after which a challenge application was applied in mthe^same manner and to fite same site as described above. A duplicate d'hai^ge application wa^ applied in the same manner to a virgin site ^J^Fe'wl9^^ the other arm. The challenge application w^ jemiory|^ and the sites were examined and graded for 18 of irritation or sensitization. A foUow-up examination was conducted at 48 hours after the challengeapplication. nradingSoile The grading scfde used throughout both the induction and challenge phases is shown in Appendix If. Beaulta: Individual panelist data are presented in Table 1. A summary of the data is presented iriTable2. Copfhininn: Fiom the results obtained with this test panel, the test article is most likely hot a primary skin irritent. The test article is most likely not a fatiguing agent. The test article is most likely not a sensitizing agent. ^BipaB^.Sanitized. Does not crisis: 810S11ARCH, (NCOSPORATOD-P.O. BOae.PHlLADBirtaA, PBNNSVLVANIA 19)01 .^. ^'.i'v^- :': 'lJ^-^l Prnj^rf Nmnhar- 93-7949H DuPoot HLO 792-93 P9y3of9 E.I. Du Font De Nemoun ft Coimpany - H'20386 Modified Draize Repeated buuft Pitch Test Study in Human Volunteer SigTMhirea Submitted by Biosearch, Incorporated: >/yi/^ Date / RaymorfdMark, M.D. Medical Director Approved by) ^ / ^ Date teETLmg,Sc.D. Vice PnMdenR, Laboratory Operations & Regulatory Anain ^^- KaH L. Gabriel, V.M.D., Ph.D. President 7-zf-^S Date ompany Sanitized. Does not contain TSCA CBB B10S6ABCH, INCOITOKATUD P.O. BOX MM - PHILAOBLHaA, PBNNSYLVAN1A 19101 - 16 - PrgTigt ffimbflr; 93-7949H E.I. Du font De Nenoura 6 Company - H-20386, as supplied. Modified Draize Repeated Insult Patch Test Study in Human Volunteers -- - 1 0 C g < w 0) 3 ^' (B P. (0 w g (? 0 ? 5 ' ^ Subject ffllfllmr 1 2 3 4 5 6 7 a 9 10 11 12 13 14 15 " 17 18 19 30 21 " 23 24 " () - 24 - 48 - - 'a) - fD t . Table l - Individual Paneliat Data Induction Phaae 1 24 4B 2 2 4 3() a* 4a 4() 24 8 5 2 48 0000 0& 06 0000 0 0 0 a 0000 0000 0000 0 D 0 0 0000 0000 0000 0 0 0 0 0000 0000 0000 0 0 0 0 0000 0000 0 0(a) 00 0 0 0 0 0000 0000 0000 0 0 0 0 0000 0000 0 0(a) 00 0 0 0 0 0 0000 0000 0000 0 0 0 0 0 0 0000 0000 0000 0 0 0 0 0 0 -0 0000 0000 OD 00 OD 0 D 0 0000 0000 0000 0000 0 0 0 0000 0000 0000 0000 0 0 0 0 00 (a) 00 0 0 0 0 0 0 Day of evere ice and anow scorms. Reading 24 hour* after application. Reading 48 houn after previous application Miased reading. Patch applied 1 day late. Discontinued for personal reaaona. 789 24 48 o0 0^ D D 24 4B ^00^ D D 24 4 00 -e ^ D 3|44B ^0 0^ D 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 - 0 0 0 0 0 0 0 0000 0000 D0O0 000 0000 0 0 0 0000 0 0 0 0 0 0 0000 0 0 0000 0000 but juat before next application. Origi Si 24 0-"0 0 ' I D 0 0 0 0 0 0 BI08BARCH, INCORPORATED - P.O. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 - (215) 739- w Pro-iect Himber: 93-7949H B.I. Du Font De Nemours Computy - H-203BG, as supplied. Modified Draixe Repeated Insult Patch Test Study in Hunan Volunteers Subject Umber 36 27 28 29 30 31 32 33 34 35 36 37 3 39 40 41 42 43 44 45 4C 47 48 49 50 (S) 24 48 - * ^ ** , D Table 1 - Individual Panelist Data (continued) 1 24 4B 2 24 48 3 i3> 24 48 4(a) 24 48 induction Phaaa 5 24 48 6 24 48 7 34 48 8 24 48 9 34 48 l0* ^4fit Origin S 24 0000 0000 00 0 0 (a) (a) 0000 0000 0000 0000 00 0^0 0 0 0 0 V000 0000 0000 - D 0(a) D D00D 00 D D 0 0 b D 0. 0. - D o .JOo ...-.- nD -000 0000 0000 0000 0000 0000 0 0 - 0 0 0 0 0 0000 0000 0000 00 00 00 0000 C 0 0 0 -- -000 0000 0000 0000 0000 0000 0000 0000 0 0 . 0 0 0000 0000 (a)0-00 0000 0000 00 0 0 0 0 -0 -0 0 0000 0000 00 000-* 00 0 0 0 0 0 0 0 0 - 0 0 0 00 0 0(a) - 0 00 00 " - - 0 0 0 0 0 0 08 0 0 0000 00(a()a)0000 0000 0000 0 00 0 0 0 0 0 0 0 0 0 0 00 0 -* - 0 - 0 0000 00 0 (9 0 0 0 0 -0 0000 0000 00 0 0(a) 000-* 0 -* 0 0 - 0 0000 0 0 0 0 0 0 0000 0000 0000 0 0(a) - 0 00 (a) 00 0000 0000 0000 0 00 00 00 (a) - 0 00 00 00 00 0 Day of severe ice and now afcorma. Reading 24 houra after application. Reading 48 houra after previoua application but juat before next application. Hired reading. Read at 72 houra. Paneliat miaaed the acheduled patch application for peraonal reaaona. Paneliat waa patched on the next acheduled application day, and the patch seriea extended until 9 induction applicafciona were Make-up patch application, (a) . Patch applied 1 day late. Discontinued for peraonal reaaona. BIOSBARCH, INCORPORATED - P.O. BOX 8598 - PHILADELPHIA, PBMSYLVANIA 19101 - (21S> 739- Project Hunber: 93-7949B B.I. Du font Oe Hecoura & Conq>any - H-20386, aa aupplied. Modified Oraize Repeated Insult Patch Teat Study in Hunan Vo-dnteera Subject Number 51 52 S 54 55 56 1 57 59 o 59 1 60 61 62 63 64 65 'f 66 S 67 '5 68 M ^ 70 % 71 S 72 5 73 ^ 74 P. 75 0 () . 24 " . 3 0 A" B "ft ' " CT 0 , . ^.ST v la) = D - W '"> Table l - Individual Panelist Data (continued) 1 8< 4? 2 31 49 3 (a) 2 8 4<) 24 4t Induction Phase 5 24 49 6 2Alfi 7 2i-ftA ULftA 9 21iA 10** 2< IP C Origin S 24 0 0 0000000000 0000000000 00000000 000000 0000 0000000000 000-0000 000 00^ e o- ^ a 0) 0 0 - 9 '* - 0(a) - "a -o-o- 0(a) 0 . 0 (a)-0 n v 0 0 0. "is QT 0 o ' 6 0 - 0 0 0 00 00 00 00 0 0 0 00 00 00 00 0 0 0 00 0 0 0 0<a) 0 0 0 0000000 00 0 0 oo oo 0 0 DO 0 0 o o 0 D 0 0 0 0 D D 0 0 00 0 0 0 0 0 0 0 0 0 0 0 0 0000" 0 0 0 0 00 00 00 0 1 0 00 00 00 00 00 00 0 0(a) 0 0 0000 0000 00 0 0(a) - o00 -* DD - o(a) o 0 0 0 0 0(b) 0 00 00 00 00 00 00 00 0 <0 0 0 00 00 00 00 00 0 0000 0000 0000 0000 00 0000 0000 00 (a) 0 0 0 0000 0000 0000 00 0-00 0000 0000 00 0 0(a) 00 0 0 Day of aevere ice and anow afcorma. Reading 34 boura after application. Reading 40 how after previoua application but juat before next application. Miaaed reading. Make-up patch application. Paneliat aiaaed the acheduled patch application Cor peraonal rwaaooa. Paneliat aa patched on the next cheduled application day, and the patch aeriea extended until 9 induction applicationa wre Patch applied 1 day late. (b) Paneliat received l make-up; technical error. Oiaeontinued for peraonal reaaona. * BZOSBMICH, INCORPORATED - P.O. BOX 58 - PHILADCLPHIA, PnK8YLVMHA 19101 - (21S) 739-4 Prgltlfft HWnbf" 93-7949H E.I. DU Font De Nemoura & Conyany - H-20386, aa upplied. Modified Draize Repeated Inault Patch Teat Study in Hwan Volunteer! Table 1 - Individual Panelist Data (continued) Subject ""itmr l 24 48 2 24 48 3 (a) 24 48 4 (a) 24 48 Induction Pha^ S 24 48 6 24 48 7 24 48 8 24 48 9 24 48 l0* ^448. C Origin S 24 1 M 0 1 ^.' 0 S c Sl ^ </ u 2, N" (C P. C 0 <B Ul 3 0 ^r 0 0 3 Si^i S' ^ 0 tw-.' 76 77 7 79 O I 82 3 84 S 86 7 9 90 91 92 93 94 95 96 97 98 99 100 <) . 24 48 , ** D . 0 0 - 0 0 0000 00 00 00 0 - 0 0 0(a) 0 0 - 0 ,, 0 0000 0 -* 0 o. .-o o O.-OL .A a jo +a) - .0 - ^ -a -o 0 0 0 0 0 0 0 0 0 00000 0 0 0 0 00000 0 0 0 0 0 0 0 0 0 0 0000000 0 0 00000 0 0(a) o 0 00 0 0 0 0 0 0 -* 0 0 0 000 .* 0 0 0 0 0(a) o o<a) o . 0 . o o 000 oo 0 0 0 0(a) 0 0 0 0 0 0 0 0 0 0 0 000 0000 0000 o(a) - 0 o o - o(a) - o oo oo' oo 0 0 0 0 0000 0000 0 0 - 0(a) - 0 00 00 0000 0000 0 0 0 0 0000 0000 0 00 000 0000 0000 0000 0 0 0 0 0000 0000 0000 0 0 0000 0000 0000 0 00 0000 0000 0 - 00 - 0(a) - 00 0 DO DO DO OD DD 00 00 00 00 00 D 00 00 00 0 00 00 00 00 00 0 Day of aevere ice and mow fcoxw. Reading 24 houra after application. Reading 48 houra after previoua application but jujfc before next application. Hied reading. Paneliafc iaed the cheduled patch application for peraonal reaaon. Paneliet waa patched on the next aebeduled application day, and the patch eria extended until induction application* wre Make-up patch application, (a) Patch applied 1 day late. Diacontinued for penonal reawona. ' BIOSBHRCH, IMCORPORATBO - P.O. BOX 8598 - PHILADKLPBIA. PBIM8TLVMIIA 19101 (215) 739- %sS/ Prg-irTT Pmbftr- 93-794911 B.I. Du Font De Hemours fc Company - H-20386, aa upplied. Modified Draize Repeated moult Patch Teat Study in Hunan Volunteers Subject inmfrftr 101 103 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 () - 24 4B ' -- Tl ft , ' ft* , (a) . D < > Table 1 - Individual Paneliat Data (continued) l 24 8 2 2* 4B 3(8) 24 48 4(a) 24 48 Induction .Phase 5 24 48 6 24 48 7 M W 8 24 48 9 24 48 10** 2i4B Origin S 24 0 0 0 0 0 0 0 0 0 00 00 00 00 0 0(a) 0 0 0 0 " 0 0 & 0 0 00 00 00 0 0 0 - a 0 t. a -o 0 J - A A 0 00-000 000000 0000 OD DD 0 0(a) 0 0 0 0 0 0 0 0 0 0 0 0 0 0 D 0 0 0 0 0 0 0 0 0 0 0 0 00 00 00 00 0 0 Ola) 6 0 0 0 0 0 0 0 0 0 0 00 0 0 0 0 0 0 0 - 0 0 00 00 00 0 0 0 D D 0 D 0 0 0 0 D D 00 .0 0 0 0 0 0 0 0 0 0 0000 0000 0000 00 0 - 0 0 - 0 0 0 0 0 0 0 0 0 0 0 0 0 00 00 00 0 - 0 0 0 0 0 0 0 0 0 00 00 0 - 0 0 0 0 0 0 0 0 0 0000 0000 00 0 - 0 0 - 0 0 0 0 0 0 0 - 0 - 0 0 0 0 0 0 0 00 00 0000 DO D 0 0 0 0 0 0 0 0 0 00 0 0(a) 0 0 0 0 0 0 0 0 0 00 00 00 0 (a) 0000 0-00 00 00 00 0000000 00 0 0(a) 0 0 0 - .* - 0 - 0 0 0 0 0 0 0 Day of evere ice and now tonu. Reading 24 hour* after application. Reading 48 houra after previoua application but juat before next application. Hiaaed reading. Paneliat iaied the cheduled patch application for peraonal reaaona. Paneliat was patched on the next acbeduled application day, and the patch aeriea extended until 9 induction applications were Make-up patch application. Patch applied l day late. Discontinued for.personal reaiona. BIOSEARCH. IHCORPORATBO - P.O. BOX B59B - PHILADELPHIA. PBWSYLVANIA 19101 - (215) 739- ..^ Project Number: 93-7949H E.I. Du Pont De HeiKturs fc Company - H-20386, as supplied. Modified Oraixe Repeated Insult patch Teat Study in Human Volunteere Table 2 - Sunnary oC Data induction Phaaa 123456789 24 48 Tgtal Sub-lecf; 120120 24 48 120120 24 4B 120120 24 48 120 120 24 4B 120 120 24 48 120120 24 48 120X20 ?4 48 120. 120 24 48 l0* ^_4ft 120 120 IT Orig 2 12 Grade 0 11C 117 115 115 116 114 94 104 91 101 101 110 107 110 109 110 110 109 17 17 10 !( 0000000000000000000000000000000000000000 00000000000000000000 ** 030 0100 20 8 20 10 10 2230 2313 3160 99 10 0 8 9 10 10 10 10 10 10 10 0 0 1 24 48 D Reading 24 hour* after application. Beading 48 houri after previoua application but juat before next application. Hifed reading. Oiacootioued for personal reaona. BXOSBMICR, IMCORPORATB) - P.O. BOX 8S98 - PHILAOSLPBIA, PBOISYLVMOA 19101 - (215) 739 ^ ^ Wf^c^,^, ,,-. mMy Project Number: 93.7949H WBIBpBffSIIW^^ Y^" DuPont ^O792'g3 E.I. Du Font De Nemoura 4c(U ropany Modified Draize Repeated buu t Patch Tert Study In Hmman Volunteer P*neH*t Number 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 26 27 28 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 w Initial* W.L.B. E.P. L.P. D.Z. J.B. R.G. J.R. N.R. J.P. B.T. J.S. P.M. P.H. D.L. V.M. CD. N.C P.C. D.S. M.F. K.G. O.M. K.B. S.L. E.R. J.R. 1.R. R.D.B. C^jXMV.. R.S. D.O. O.M. B.T. N.S. H.P. L.C. E.W. B.C. S.A. H.W. S.R. S.B. M.C. B.C. D.H. J.H. R.S. J.I. W.W. L.W. M.H. G.S. C.S. O.B. E.P. L.S. i.H. T.D. D.C. A.L. EANEUSTUST A| e Oouprikm A2xfe* UimByjayaJ "^"SruEySvh.i,i.i..------------------ 29 Uvfrnflaffd 52 HoiMomte 39 HixHMMter ^&t^^^--^------WbM^if OUhWNlwr a s 41 rinmmilrOT 35 29 H> ^^H^--Cm--i|M.CIt 31 HoMUMtar 34 NMM 39 HoOMButor 32 MRIM 4 4 Hoamutar a19 HnrnMBiif a . A "W .W- . H. U 29 Hoiiim--9f 27 S&WR----MAk------ 32 Hoacmatar fl-- ' ; Mnu<D^iB^^uMfic--^ 22 CMu 49 SetoolAidt 29 HomeiMdu 37 Stodihnon 19 Studart 47 UMmiiloved 79 lItHntnurTi 24; IlniMumfctt 34 Homenukm' 30 ; HOBMBUUEBT 28 ' Homwter 29 . Komeauker 46 HomeaukOT 24 Hoinenulwr 19; Onk 40 ffoirmmtw 33 HoaKauker ---w-m^n--ss.m-w. 42 Hoawmtker 39 ChMkCMhfer 21 ; CMHter 43 Cro--ingCoiil 38 ' Scactny 46 : MKMMOpmto 26 Driver 29 HomMkr 21 Student 38 hctotyworit 41 Homwuter 53 , Homeauker 44 Cuhler 20 Student 45 Homemaker 44 HoBMRMlMr 34 Homemalwr 35 Unmployd 44 BmAtMndint 19 Mak--Lampthde M ^ T w r t o e * PadcOSn.Aita^Wt.SewM vU^W^^rBlUlw-- "--I-*.--! m Ivy, SeMomI Itoyfcver HMPKW DMVOA( rduCOuA Ott SlNU*h . OBt B--lslB* ...ftfilcfIHUf SuKMUUf nsywws cm ^BkB^i^JB^tuUU^lf AA i^JmJx--n Tooiatoe* So--onal ftnfcfflin - Sfaw ni--irt^iinnui- Sc--omi, Hnyfevcr Hqrfever, Seaional . FinridDDin Sbiu* Dog,Hayfever,R*gweed,Sulfi Atthnu rv*uMei-i Sbuu ' cm ] x^. B.-^yi*e- v- - c i Out DurtOccukmiJIy . - ArimdHair . Hayfever lUyfever Durt. ArthuM Sbur ftAidlBn Ttuiu CitHJir Hiyfever BMllpaw^s"D"o"e^seno'tcDon<f'a-"inT.ScCoA,,c,,:,,^c - 23 - |&. / : ! ^ P^H ^'- -'S& Protect Number: 93-7M9H DuPont HLO 7W-^1 Appendix i E.I. Du Font De Nemoun IcOnnpxny Modified Draize Repeated buw t Patch Teftt Study in Human Volunteers PANELIST LIST (continued) PuwHf Number Initial* Agi OocupHton Allergic* 61 K.H. 62 C.S. 63 J.K. 41 BdtDd--r 37 TBecner'tAjqe 25 Unemployed 64 T.S. 38 Uiwmpbyd : 65 S.S. 38 Hoinemafcer 66 A.W.N. 46i fulfill/in ; 67 H.H. 54 IX-Hid : 68 C.C. 46 U--Jw^i^e^B^N-ULBUwM 69 V.G. 21 70 P.J. 37 Homemaker Suuu 71 M.P. 72 J.P. 42 Homemaker 46 Ho--maker 73 A.V. 74 W.V. 75 R.R. 20 Babrtt(er 41 rmSufvua 29 76 J.W. 77 K.G. 78 M.V. 7 E.H. 80 M.G. n K.H. 82 J.M.k. 24 Hoawauter 42; HooMnufca 34 TIUBtiniff^TT 40; Supmfwt \ 'JU--j^^Bb--^^--IIR----1------ " 46 Hoihcmalccr 27 HoiMoiater 13 D.R. 9ft I^A--lM--jMk^rf^ M M.G. 19 Sftidntt - B5 M.K. 48 ComtnictiDft M C.S. 39 Ih-wmilT* w s-s. 35 tl^------^r^ 88 C.M. 24 ftdMr 89 A.T. 18 Student 90 P.W. 42: Homemaker - 91 M.R. 53 HMMmaker 92 C.R. 37 TUfliTfmikff 93 A.P. 41 Avon Lady PfeidcOHn <H ].G. 35 Unemployed 9S l.P. 43 Unemployed 96 I.D. 31 Homemaker 97 M.C. SO HoiBemaker 98 R.F. 18 Student Duit 99 M.E.F. 48 Cook 100 D.L. 271 HoniCTater 101 M.S. 191 Student | 102 C.G. 103 M.J. 18 Student 36 Homemdter 10 R.B. W43E Xii&un*ifetn^^i--*b---- 105 S.M. 32: Nine'* Aide 106 M.L. 26 BucerKtag 107 I.G. 51 Hoincmaker 108 C.U. 49 Homemaker - 1 109 J.N. 19 Student FbDen 110 J.J. 22 Metal Worker Ragweed Ill I.W. 112 M.P. 113 R.B. 52 Homemaker 19 Student 24 HMaemaker 114 A.B. 115 A.E. 26 Roofer 41 Homemaker 116 O.B. 37 Maintenance 117 S.S. 41; Unemployed 118 C.A.D. 119 S.B. 55' Homemaker 38; Homemaker 120 MA 18 Student ^^^ ^ Company Sanitized. Does no? contain TSCA C : Project Number: 93-7M9H DuPont HLO 792-93 Appendix D E.I. Du Font De Nemoure & Company H-20386 Modified Draize Repeated Insult I^atchTest Study in Human Volunteers GRADING SCALE Human Patch Test Studies Reading latertuetatiaa 0 negative suspicious 1+ slight erythema ', 2+ well defined erythema 3+ erythema with induration 4+ erythemawith ulceration DEFINITIONS* Sensitization is a phenomenon which manifests itself by local effects on either skin or mucous membranes. It differs from primary irritation in that it may also involve tissues remote from the site of application. These reactions represent an allergy to a chemical which is not obtained on first 'contact, but requires a number of prior exposures for development. Repeated patch applications of substances to both man and animals reveal that certain substances which, at a given concentration, do not produce primary irritation may elidt severe skin reactions after a number of exposures. Nevertheless, these reactions may not be considered incidents of sensitzation since after 10-14 days of rest the skin recovers its original resistance to injury by the substance. For the lack of a better term such reactions have been called "skin fatigue". This latter term is a misnomer in that it does not imply a condition in which the skin his lost significant normal physiological function. This phenomenon consists of a subtle' change in which the skin no longer exhibits its original refractoriness or resistance to the continued or repeated action of an agent. * Draize, J.H. 1959. Appraisal of the Safety of Chemicals in Poods, Drugs and Cosmetics. In DERMAL TOXICITY, p.46-53. Topeka, Kansas: Association of Food and Drug Officials of the United States. Company Sanitised. Does not contain TSCA CF IHOSEARCH, INCORPORATED P.O. BOX IS9B PHILADELPHIA, PENNSYLVANIA 19101 .. IS -