Document Z8RwMOM6BGmMj6KpE63xXEaX7

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 Affrime for E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box 50 Nevark, Delaware 19714 Study Monitor John R. Bamberger Medical Research No. Company Sanitized. Does not contain TSCACBS Page 1 o f 25 Material T ested Physical Fora; Synonymss Compositions GENERAL INFORMATION Control Material DuPont BLO 792-93 Material Tested? Physical Fores Synonyms s Compositions ompany Sanitized, Does not contain TSCA BB GENERAL INFORMATION (CONT.) DuPont BLO 792-93 Stability: In the absence of visible evidence to the contrary, the test asterials vere assumed to be stable under the conditions of administration. Sponsor: DuPont Fibers B. I. du Pont de Nemours and Company Wilmington, Delavare Study Initiated - Completed: 10 January 1994 - 25 February 1994 In-Life Phase Initiated - Conpleted: 10 January 1994 - 17 February 1994 -3- .Sanitized. Does not contain TSC6 B3 DUPONT CENTRAL RESEARCH AND DEVELOPMENT HASKELL LABORATORY FOR TOXICOLOGY AND INDUSTRIAL MEDICINB DuPont HLO 792-93 Joyce M. Materniak DuPont Fibers Chambers Vorks 25 February 1994 100-Person Human Patch Test with H-20385 (Control Item) and H-20386 (Test Itea) Attached is a report from Biosearch, Inc. (Project No. 93-7949H). Included in the report are patch test methods, results, and conclusions. The purpose of this study vas to determine the potential of H-20385 (Control Item) and H-20386 (Test Item) to cause delayed contact hypersensitivity in humans. During the induction and challenge phases of this study, H-20385 (Control Item) and H-20386 (Test Item) produced no adverse skin responses in 100Z and 100Z, respectively, of those subjects vho were active participants. Based upon the effects observed with the test materials 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. John R. Bamberger, B.S Toxicologist PompsftySanitized. Bees notcontain TSGACBS - 4- DuPont HLO 792-93 BIOSEARCH INCORPORATED P.O. Box 8598, Philadelphia, Pennsylvania 19101 Telephone: (215) 739-4499 Pax: (215) 423-9210 Project Num ber: Teating Facility. Isat Artide: Teat Artide D escription: Teat A rtide Received: Study Initiated: Date of Reportleat: Object of Test: Reference: M ethod of Test: 93-7949H Biosearch Incorporated 3408-50 T Street Philadelphia, PA 19134 E.I. Du Pbnt De Nemours Sc Company P.O. Box 50, EDcton Road Newark, DE 19714 H3385 12/14/93 01/10/94 02/25/94 Study com pleted- 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 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.R Draize and published by die Association of Food and Drug Officials of the United States. Tsa t-gneJ: 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 not contain TSCACBS 5 Project Number: 93-7949H DuPont HLO 792-93 Page 2 of 9 E.I. Du Pont De Nemours & Company - H-20385 Modified Draize Repeated Insult Patch Test Study in Human Volunteers Method of Test: (continued) Patch Preparation: The test 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 (Johnson & Johnson, New Brunswick, NJ 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 application was identical to the first and remained in place 24 hours. This procedure was repeated on Mondays, W ednesdays 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 m anner and to the same site as described above. A duplicate challenge application was also applied in the same m anner to a virgin site (previously untreated) on the other arm. The challenge application w as 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. G rading Scale: 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. -m p a n y San,f,zed. Does not confai T se* eB? HIOSliARCH, INCORPORATED - P.O. BOX SS98 - PHILADELPHIA, PENNSYLVANIA 19101 - 6- ji Project Number: 93-7949H ! DuPont HL0 792-93 Page 3 Of 9 E.I. Du Pon' Dl Nemours 4c Company - H-20385 Modified Draize Repeated Insult Patch Test Study in Human Volunteers Signatures: Submitted byBiosearch, Incorporated: Date f Approved by: Date Sc.D. Vice President, Laboratory Operations & Regulatory Affairs Karl L. Gabriel, V.M.D., Ph.D. President Date Company Sanitized. Does not contain TSCA6E9 BIOSBARCH, INCORPORATED- P.O. BOXtSM - PHILADELPHIA, PENNSYLVANIA 19101 -7- Project Muhr; 93-7949H 8.1. Du Pont 0 Nemours fc Company - H-20385, as supplied. Modified Draize Repeated Insult Patch Test Study in Human Volunteers DuPont I1L0 792-93 Company Sanitized. Does not contain TSCA CBS Table l - Individual Panelist Data Induction Phase Subject l 2 3 4 5 7 9 10 11 12 13 14 15 1C 17 19 19 20 21 22 23 25 i 24 48 00 00 00 0 00 00 00 00 00 00 00 00 00 00 00 20 00 00 00 00 00 00 00 00 00 2 24 48 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 3(a) 4(B) 24 48 24 48 00 00 00 00 00 0D 0o 00 00 00 00 00 00 00 00 00 0 0(a) 0 0 00 00 00 00 00 00 0 0(a) 0 0 00 00 00 00 00 00 00 00 00 00 0D DD 00 -0 00 00 00 00 00 00 00 00 0 0(a) 0 0 5 23L -0 -0 D .0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD -0 00 -0 00 00 00 5 00 00 0D 00 00 00 00 c0 00 00 00 00 00 00 00 00 00 00 DJ 00 00 00 00 00 00 7 1-1S 00 00 HD 00 00 00 00 00 00 00 00 00 0 00 00 00 00 00 DD 00 00 00 00 00 00 8 ai. 19 00 o0 XL .XL 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 00 00 9 21_ifl 00 00 D B ..... --00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 00 00 () * 2 4B . (*) * D" Day of severe ice and snow storms. Reading 24 hours after application. Reading 48 hours after previous application but just before next application. Missed reading. Patch applied l.day late. Discontinued for personal reasons. Originai. Site 2U1 Virgin Site 21ii 00 oo 00 oo D B - -- -4) D ---- 00 o0 00 oo 00 0o 00 00 00 oo 00 oo 00 0o 00 0o 00 00 0o oo 00 0o 00 00 00 0o 00 00 00 00 D0 DD 00 00 00 00 00 00 00 00 00 00 00 00 BIOSBARCH, INCORPORATED - P.O. BOX 8598 - PHILADELPHIA, PBOtSYLVANIA 19101 - (215) 739*4499 Pra-im r-f 93-7949H E.I. Du Pont De Nemours 6 Company - H-20305, as supplied. Modified Draize Repeated Znault Patch Test Study in Human Volunteers Company Sanitized. Does not contain TSC CBI Table l - Individual Panelist Data (continued) Subject 26 27 . 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 (a) m 24 . 48 ** * . D- 1 24 48 00 00 -0- 0 00 00 -0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 2 31. ,48 00 00 0a 00 00 00 00 00 00 00 00 00 00 00 -0 00 00 00 00 00 00 00 00 00 00 Induction. Phase 3 <s) 24 48 4 (s) 2U1 si 31 48 6 3iil 0 0(a) 0 0(a) a0 0D 00 00 00 00 00 00 0 0(a) 00 00 00 00 0 o(a) 0 0(a) 0 0(a) 00 00 00 0 0(a) 00 00 0 0(a) 00 00 00 00 IWal 0 DD DD 00 0 .0 00 00 00 - .* 00 -0 00 00 00 00 -0 00 00 00 00 0 -0 00 00 0 -0 00 00 00 00 00 00 0 -* -0 -0 0 00 -0 0 _ 0 0(a) - 0 0 0(a) 0 0 -0 00 00 00 &g DD 00 00 00 00 00 00 00 00 c- 0 0 -0 00 00 00 00 00 00 -0 00 00 0 7 24 4B 8 24 48 00 00 -0- 0 DD 00 -0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 - 0 -0 DD 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 9 10** 31 18 3 L - 1 1 hfillSIK(fi Original Virgin Site Site 24 48 31 18 00 00 0o 00 00-- 00 oo ...... ...........-------------0 - 0 - ------- f r -- o DD DD D0 00 00 00 00 00 00 00 00 00 00 00 00 0 0 00 00 00 00 00 00 00 00 00 00 00 00 00 0 0 DD D0 00 00 00 0 0 0 0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 0 0 00 00 00 0 0 00 00 00 0 0 00 00 00 00 00 00 00 00 00 00 00 i ! a ft i Day of severe ice Reading 24 hours after application. Reading 48 hours after previous application but just before next application. Missed reading. . Read at 72 hours. Panelist missed the scheduled patch application for personal reasons . Panelist was patched on the next scheduled application day, and the patch series extended until :9 induction applications were applied. m e - u p patch application. (a) - Patch applied i day late. Discontinu--ed for yp*e*r*s'o*na*l arveaaasvoinMs.. ' BIOSBARCB, INCORPORATED - P.0. BOX SS98 - PHILADELPHIA, PENNSYLVANIA 19101 - (215) 739-4499 Pr"W l' 93-7949H b .i . Du Pont D*s Nemours ft Company - H-203BS. as supplied. Modified Draise Repeated Insult Patch Test Study in Human Volunteers DuPont KLO 792-93 Sanitized. Does not contain TSC CB1 Table l - Individual Panelist Data (continued) Subject aatsc l 24 48 2 aite 3(a) 2UU 4(a) 24 48 Induction Fhsw 5 67 24 48 24 48 24 40 9 10* 24 48 21--It gn.ii-- Original Site Virgin Site 21_ii 21-11 51 - ST 53 54 55 56 I 57 SB o 59 60 61 62 63 64 65 66 67 66B9 70 71 72 73 74 75 00 o0 00 00 00 00 00 00 00 00 00 00 00 00 00 0 0 00 00 00 00 00 00 00 00 00 00 0` o 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 "0" 0 00 00 00 00 00 00 00 0 0(a) 00 00 00 00 00 00 00 0 0(a) 0 0(a) 00 00 00 00 00 00 00 0 IT 0 .* - - 00- 0 0(a) 0(a) 0 0 0 0- 0 0 0- 0 0 0 0 00 0 0D D 00 0 00 0 00 0 00 0 00 0 0- 0 0 0 0- 0 0 0 0 00 0 00 0 0 0 0 0(a) 0- 0 Otar 0 0 0 0 0 0 0 0 0 D 0 0 0 0 0 0. * 0 0 0 0 0 0 00 0~ 0 00 00 00 00 00 00 00 00 00 6D D 0 00 00 00 00 c0- D 0(a) 0 00 00 00 00 00 00 00 0" 0 ..-- ft" 0- 0 0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD DD 00 00 00 00 00 00 00 00 00 00 DD DD 00 00 00 00 00 00 00 00 0 o(a) 0 0 00 00 00 00 0 --- 0 0 0 0 0 0 0 0 0 0 D 0 0 0 0 0 D 0 0 0 0 0 0 0 0 0 0- 0 0 0 0 0 0 0 D 0 0 0 0 0 D 0 0 0 0 0 0 0 ---- ------------- 00 0 0(b) 00 DD 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 00 DD 00 00 00 00 00 00 00 - 00 DD 00 00 00 00 00 00 00 00 00 DD 0o 00 00 00 00 DD 00 00 00 00 00 00 00 (s) 24 4B - * " (a) " D Day of severe ice and snow storms. Reading 24 hours after application. Reading 4B hours after previous application but just before next application. Missed reading. Make-up patch application. Panelist missed the scheduled patch application fo. personal reasons. Panelist was patched on the next scheduled application day, and the patch series extended until 9 induction applications were applied. Patch applied 1 day late. (b) Panelist received l make-up; technical error. Discontinued for personal reasons. * BX08BARCH, INCORPORATED - P.0. BOX 8598 - PHILADELPHIA, P H M8 Y L V A N X A 19101 - (215) 739-4499 r Proiaet Muh.r. 93-7949H B.I. Du Pont De Nemours Company - H-203B5, as supplied. Modified Draize Repeated Insult Patch Test Study in Human Volunteers Table 1 - Individual Panelist Data (continued) Subject 12 iti. 48 a i i 3(B) 18 4 (s) 1148 Induction Phase 5 24 40 6 24 40 7 21-11 0 21-11 9 10** 21-11 21--11 rhal *Tl*ItT Original virgin Site Site 24 40 24 48 76 77 7S 79 00 01 02 03 04 05 06 07 00 9 90 91 92 93 94 95 96 97 90 99 100 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 00 00 Q0 00 00 00 00 00 00 00 00 00 00 00 00 o0 00 00 00 00 00 00 0 - 00 00 0 0(a) o. n 00 00 00 00 00 00 00 00 0 0(a) 0 0(a) 0 0(a) 0 0(a) 00 00 00 00 00 00 00 0(a) 00 00 0 00 o 00 00 00 00 00 0 0(a) 00 00 00 00 00 0 0(a) 0(a) 00 00 00 00 00 0 00 00 0 0_* o 00 00 00 00 00 00 00 0 0 * _* 00 00 00 0 0 0 0 0 0 0 D 0 0 0 00 0 00 00 00 - tat 0---0- -o V 0 00 00 0 0 0 0 00 00 0 0 00 00 0 0 00 00 0 0 00 00 0 0 00 00 0 0 00 00 0 0 00 00 0 0 00 o0 0' 0 0 0 0 0 0 0 00 00 0 0 00 00 0 0 00 00 0 0 00 00 0 0 00 00 0 0 00 00 0 0 00 00 0 0 00 00 0 0 00 00 D D DD DD 0 0 00 00 0 0 00 00 0 0 0 0 00 00 00 00 00 0c 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD DD 00 00 00 00 00 00 00 00 0o 00 00 00 00 00 00 00 00 0o 00 00 00 00 00 DD DD 00 (s) Day of severe ice and snow storms. 24 Reading 24 hours after application. 40 Miased^reading1* * ft*r previou8 application but just before next application. Fi ** D n ^ t 1i c L d u i Z H ^ . ^ i < ,cj" dul*d P*tc* application for personal reasons. Panelist was patched on the Hake d*y ' *n d the P*tch series extended until 9 induction applications were applied. * PPllC*tio?- <> - ptch applied 1 day late. Discontinued for personal reasons. Q BIOSKARCH, INCORPORATED - P.0. BOX 0590 - PHILADELPHIA, PENNSYLVANIA 19101 - (215) 739-4499 DuPont HL0 792-93 Company Sanitized. Does not conti J\ i NJ I as ' Pra-U-t- w<f^tr- 93-7949H B.I. Du Pont De Nemours t Company - H-20385. as supplied. Modified Draize Repeated Insult Patch Test Study in Human Volunteers Subject pywfcir 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 ne 119 120 i 24 48 00 00 a0 c0 0 00 00 00 D0 DD 00 00 00 00 00 00 0D 00 00 00 2 24 48 00 00 a0 00 00 00 00 00 DD DD 00 00 00 00 00 00 DD 00 -0 00 Table 1 - Individual Panelist Data (continued) Induction Phase 3(B) 4 (s) 5 11 .if ll_ft 24 48 00 00 00 00 o 0(a) 0 0 00 -0 00 0 0(a) 0 0 0D DD DD 00 00 00 0 0(a) 0 0 00 00 DD 00 DD 00 DD DD 00 DD 00 D 0 D_* 00 00 00 00 -0 00 00 -0 00 00 0 -* - 0 00 -0 -0 DD DD DD 00 0 0(a) 0 0 0 0(a) 0 0 0 _* 0 0(a) 0 0 - 6 21 00 00 00 DD 00 00 00 DD Db 0 00 00 00 00 00 DD 00 .0 -0 7 14-18 00 00 -0 00 DD 00 00 00 DD DD 00 00 00 00 00 00 DD 00 00 00 8 24 48 00 0 00 DD 00 00 0 DD DD 00 00 00 00 00 00 DD 00 00 00 9 24 48 00 00 0o 00 DD 00 00 00 DD DD 00 00 00 00 00 00 DD 00 00 00 10* 2 i__1ft 00 00 00 00 nun Original Site 14.4ft Virgin Site M 4 00 00 00 Do 00 00 00 DD DD 00 00 00 00 00 00 DD 00 00 00 00 00 0 ' 00 DD 00 0o 00 DD DD 00 00 0 00 00 00 DD 00 00 00 (s) Day of severe ice and snow storms. 24 Reading 24 hours after application. 48 Reading 48 hours after previous application but just before next application. Missed reading. Panelist missed the scheduled patch application for personal reasons. Panelist was patched on the application day, and the patch series extended until 9 induction applications were applied. Make-up patch application. (a) Patch applied 1 day late. D Discontinued for personal reasons. BIOSBARCH. INCORPORATED - P.O. BOX BS9B - PHILADELPHIA, PENNSYLVANIA 19101 - (21S) 739-4499 DuPont HLO 792-93 Company Sanitized. Does not cont; Project 93-7949K E.I. Du Pont De Nemours Company - H-203S5, as supplied. Modified Draize Repeated Insult Patch Test Study in Human Volunteers Table 2 - Suonary of Data 1 24 48 Total Subjects; 120 120 Grade 2 24 48 120 120 3 24 48 120 120 4 24 48 12Q 120 indurti!.Hw 56 24 48 21-11 120 129 120120 7 24 48 120 120 8 21 41 220 120. 9 d i.ll 120 120 10** 21__U OiaUflim O riginal V irgin Site' S ite 24 48 24 48 17 17 _.------120 120 -- 120-120- I 0 116 117 115 116 116 114 94 104 91 101 101 110 107 110 109 110 110 109 17 17 107 105 107 105 u> 00 00 00 0 0 00 00 00 00 0000 00 00 s 1+ 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 00 00 2+ 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 00 00 3* 00 00 00 00 00 00 00 00 0 000 0O 00 4+ 00 00 00 00 00 00 00 00 0000 00 00 2 0 2 1 1 0 20 8 20 10 10 0 3 0 1 0 0 1 0 0 02 02 D 2 3 3 3 3 6 6 8 9 9 9 10 10 10 10 10 10 10 0 0 13 13 13 13 24 48 D Reading 24 hours after application. Reading 48 hours after previous application but Just before next application. Missed reading. Discontinued for personal reasons. DuPont HLO 792-93 Company Sanitized. Does not contain TSCA r BIOSBARCH, INCORPORATED - P.O. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 (215) 739-4499 DuPont KLO 792-93 BIOSEARCH INCORPORATED P.O. Box 8998/ Philadelphia, Pennsylvania 19101 Telephone: (215)7394899 i Fax: (215) 4234210 !i Project N um ber: leafing Facility: 93-7949H i Bioecarchj Incorporated 3408*50- T Street Philaddphia, PA 19134 Sponsor: leatA rtide: E.I. Du Pont De Nemours & Company P.O. Box 50, Elkton Road Newark, DE 19714 _____ I . H-20386 Test Article Pgam ptinn: Test Article Received: | Study Initiated: Date of Report: lest: 01/MP94 : Study Completed: 02/17/94 02/25/94 Modified braize Repeated Insult Patch Test Study in Human Volunteer s. Object of Test: To determine^the irritating, fatiguing and sensitizing properties of Reference: M ethod of Test: employed in carrying out this test was similar to that in "Appraisal of fite Safety of Chemicals in Foods, Drugs dies" by J.H. Draize arid published by fite Association of Drug Officials of fite United States. Test Panel: The test involved the application of the test article to the u p p er 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 pandists completed the study (see Panelist List, Appendik 1). These pandists were all determ ined to be in good general health and free of any visible skin disease or anomaly in the area to bn patched. Each panelist w as required to read, understand and sign Ian informed consent statem ent. Does not conlaln ' 14 ftpjcct Number: 93-7949H E.I. Du Pont De Nemours & Gonipany - H-20386 DuPont HLO 792-93 Page 2 of fi Modified Draize Repeated Insui Patch Test Study in Human Volunteers Method of Teat: (continued) Eatch , . , as H i teat rttefo wp tested as supplied. A portion of test article, approxim ately one Injfh square, was applied to the appropriate skin site and covered w ith 2" Dermicel* hypoallergenic doth tape 0ohnson A Johnson, New Brunswick, NJ 08903). Induction r The paid* was applftKi to its designated contact site on foe upper ,, and remained in place for 24 hours. At the end of this period, foe "'tch w as removed and foe site was examined for any dermal respcjnse. The panelists w ent then rested for a 24-hour period after which foe skin site was again examined. A patch was then applied to the samd site as previously used. The second application was identical to foe first and remained !)? place 24 hours. This procedure was repeated on Mondays, W ednesdays and Fridays until a series of nine applications had been m ade., Patch applications made on Friday were removed by foe panelist on Saturday. The panelists examined foe rite for any dermal response and sm arted their observations prior to the next application. The same rite eonfinued to be used throughout the study, m foe event when one InduCfton patch application was missed, the panelist v s allowed to at foe end of foe induction patch period. This was done on fo eM ftid ay following the last scheduled induction p at h application. Severe ice aird snow storms in January made travel to the laboratory impossible ft some of the panelists on several test days. Adjustments in the test 8chd lie ftw individual panelists are shown in Table 1. Challenge Phi nei After the 9th application, a rest period of approximate!) 2 weeks elapsed after which a challenge application was applied in the same m anner and to foe same site as described above. A duplicate chal tenge application w as also applied in the same m anner to a virgin site previously untreated) on foe other arm. The challenge application wi is removed after 24 hours and foe sites were examined and graded for si( ns of irritation or sensitization. A follow-up examination was conduct* l a t 48 hours after foe challenge application. Grading Scale The grading scale used throughout both the induction and challenge phases is shown in Appendix II. Results: Individual panelist date are presented in Table 1. A summary of the data is presented in Table 2. Conduaion: Horn the results obtained w ith this test panel, the test article is most likely not a primary skin irritant. The test article is most likely not a fatiguing agent. H ie test article is most likely not a sensitizing agent. iferapaBg .Sanfiked Does noi c: ita; ' cm 8IOSUARCH, INCXW POajvrBD - P.O. 8 0 i * u - M IL A W trtflA , PfiNNSVlVANIA 19101 Egbert Number: 93-7949H DuPont HLO 792-93 Pap 3 of9 E.I. Du Pont De Nemours 4c Company H-20386 Modified Draize Repeated Insult Patch Teat Study in Human Volunteers Signatures: Submitted by Biosearch, Incorporated: Study Director k ft Raymond Mark, M.D. Medical Director Approved by) Sc.D. Laboratory Operations 4c Regulatmy Affaira jahA M d u jJl KaH L. Gabriel, V.M.D., Ph.D. President Date ompany Sanitized. Does not contain TSCA CBi BIOSEA*CH INCORPORATED. P.O. BOXISM- PHILADELPHIA, PENNSYLVANIA 19101 - 16 - Project MiimKr - 93-7949H B.I. Du Pont De Nemours t Company - H-20386, aa supplied. Modified Draice Repeated Insult Patch Test Study in Human Volunteers Nj 9 9 Ito atcoo p(D, oO o oo 5" Table 1 - Individual Panelist Data Induction Phase Subject Wwawrr 1 2 3 4 5 6 7 8 9 10 11 12 13 14 IS 16 17 18 19 20 21 22 23 24 25 (8) m 24 48 (a) O i 24_ifi l 2A.it 3(s) 4(a) 5 24 49 2 L U 2A-1& 2A...19 7 24 48 a 24 48 o 2A AB 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 a0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 0 00 00 00 00 00 00 0 0(a) 00 00 00 0 0(a) 00 00 00 00 00 0D 00 00 00 00 00 0 0(a) 00 0 0D 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD -0 00 00 00 00 00 _0 -a DD 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD -0 00 -0 00 00 00 00 DD 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 00 00 00 DD 00 00 00 00 00 00 00 00 00 0 00 00 00 00 00 0D 00 00 00 00 00 00 00 --Ox DD 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 00 00 0o -o- DD 0o 0o 0o oo oo oo oo oo 9o oo oo oo oo oo oo DD oo 0o 00 00 00 00 Day of severe Ice and snow storms, Reading 24 hours after application. Reading 48 hours Missed reading. after previous application but just before next application. Patch applied 1 day late. Discontinued for personal reasons. rKml,lOTIT Original Virgin Site Site 24 48 24 4S 00 - DD 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 00 00 00 0 DD 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 00 00 BIOSEARCH, INCORPORATED - P.O. BOX S59B PHILADELPHIA, PENNSYLVANIA 19101 - (21S) 739*4499 Project Humber: 93-7949H B.l. Du Pont De Nemours a Company - H-203B6, as supplied. Modified Draise Repeated Insult Patch Test Study in Human Volunteers Table 1 - Individual Panelist Data (continued) Induction Phase Subject 26 27 28 29 30 31 32 33 00 34 1 3S 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 1 24 48 00 00 00 tr 0 00 "0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 2 24 48 00 00 00 00 00 00 00 00 00 00 00 00 00 00 -0 00 00 00 00 00 00 00 00 00 00 3 is) 4.A 3 4(S) 2 1 40 5 24 48 0 0(a) 0 0(a) 00 0D 00 00 00 00 00 00 0 0(a) 00 00 00 00 0 0(a) 0 0(a) 0 0(a) 00 00 00 0 0(a) 00 00 0 0(a) 00 00 - 0(a) DD 00 00 00 - _ 00 00 -0 00 00 -0 00 -0 00 00 00 0 * 0 -* 00 0 0(a) 0 0(a) -0 00 00 00 DD 09 00 00 -0 00 00 00 00 0 00 > 00 00 00 -0 -0 -0 0 . -0 00 00 6 24 48 00 00 00 DD 00 00 00 00 00 00 00 00 0 00 .0 00 00 00 00 00 00 0 00 00 00 7 31.40 00 00 00 DD 00 0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 8 24 48 00 Ox 0 09 DD 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 9 34 1 0 0 A D 0 0 0 0 6 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 10** 00 0 0 0 0 0 Original Site 34 41 00 00 ----- A 0. . DD 0 0 0 0 .0 0 0 0 D 0 0 0 0 0 0 0 0 0 0 0 0 Virgin Site 31. H 00 00 - 0-0 DD 00 00 00 00 00 00 00 00 DD 00 00 00 00 00 00 00 00 00 00 00 00 (s) Day of severe ice and snow storms. 24 Reading 24 hours after application. 48 Reading 48 hours after previous application but just before next application. Hissed reading. . Read at 72 hours. the scheduled patch application for personal reasons. Panelist was pstched on the ** i.n -.a w *PPlic*tion day, and the patch series extended until 9 induction applications were applied. D Sh/ Ppllcation- <> * ptch applied 1 day late. Discontinued for personal reasons. * BIOSBARCH, INCORPORATED - P.0. BOX 8598 - PHILADELPHIA. PENNSYLVANIA 19101 - (215) 739-4499 DuPont HLO 792-93 pan? Sanitized. Does not contain TSCA e f . ! : Pro->e M h.r. 93-7949H B.I. Du Pant De Nemours & Company - H-20386, an supplied. Modified Draize Repeated Insult Patch Teat Study in Human Volunteers Table l - Individual Panelist Data (continued) Subject 1 21.4? 2 24 48 3(B) a .M 4 (s) 24 48 Infraction Phaan S6 21-44 24 4B 7 24 18 8 24 4S 9 2114 10** 24 4B Original Site 24 48 Virgin Site 24 48 51 52 53 54 5S 56 s S7 58 vD 1 59 60 61 62 63 64 65 p 66 67 I 68 69 smo 70 71 3 72 sS5u-'' 73 74 .0 , 75 "mGO (S) 24 E *8 . 00 00 0o 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 d 0. 00 00 00 00 00 00 0 0(a) 00 00 00 00 00 00 00 0 0(a) 0 0(a) 00 00 00 00 00 00 00 0 o .* . 00 - 0(a) 0 0(a) -0 -0 00 -0 00 0D 00 00 00 00 00 0 - 0_ * 00 -0 00 00 00 0 0(a) 00 - 0(a) - "0" 00 0 .0 -0 00 00 00 00 00 DD 00 00 00 00 00 00 0 .* 00 00 00 00 00 -0 00 00 0 tr 00 00 00 00 00 00 00 00 DD 00 00 00 00 00 0D - 0(a) 00 00 00 00 00 00 00 00 00 a. 0 nV D 0 -0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD DD 00 00 00 00 00 00 00 00 00 00 DD DD 00 00 00 00 00 00 00 00 0 0(a) 0 0 00 00 00 00 00 00 0o 000 00 00 00 00 00 00 DD 00 00 00 00 00 DD 00 00 00 00 00 00 00 00 0 0 0(b) 00 DD 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 00 DD 00 00 00 00 00 00 00 o0 DD 00 00 00 0o 00 00 00 00 00 DD 00 00 00 00 00 DD 00 00 00 00 00 00 00 Day of severe ice and anew a t o m s . Reading 24 hours after application. Reading 48 hours after previous application but just before next application. Missed reading. . Make-up patch application. Panelist aissed the scheduled patch application for personal reasons. Panelist was patched on the next scheduled application day, and the patch series extended until 9 induction applications ears applied. _*tch i day late. (b) Panelist'received l make-up; technical error. Discontinued for personal reasons. * BIOSEARCH, INCORPORATED - P.0. BOX 8598 - PHILADELPHIA, P M t S Y L V M H A 19101 - (215) 739-4499 DuPont HL0 792-93 Project Number; 93-7949H E.I. Du Pont De Hemours & Company - H-20386, as supplied. Modified Draize Repeated Insult Patch Test Study in Human Volunteers Table I - Individual Panelist Data (continued) Subject BOfasC 1 24 48 2 24 48 3(B) 24 48 4(B) 24 48 Induction Phase 5 24 48 6 21_1ft 7 2i.ll 8 24 48 9 10** 24 48 2ft-j U ChlllffIMft Original virgin Site Site 2i_lft 24 48 101 102 10.3 104 105 i 106 107 NH-i* 108 109 6 110 111 112 113 114 115 116 117 118 119 120 00 00 00 00 -0 00 00 00 DD DD 00 00 00 00 00 00 0D 00 00 00 00 00 00 00 00 00 00 00 DD DD 00 00 00 00 00 00 DD 00 -0 00 00 00 00 00 00 0 0(a) 0 0 Q0 -0 00 0 0(a) 0 0 0D DD DD 00 00 00 0 0(a) 0 0 00 00 00 00 DD DD DD DD 00 DD 00 DD 0 _* 00 00 00 00 -0 00 00 0 00 00 00 0 -0 -0 -0 DD DD DD 00 0 0(a) 0 0 0(a) 0 0 0 0_ * 0 0(a) 0 0 - 00 0n 0L 00 D0 00 00 00 DD DD -0 00 0 0' 00 00 00 DD 00 -0 -0 00 00 0 .0 00 DD 00 00 00 DD DD 00 00 00 00 00 00 DD 00 00 00 00 00 a0 00 0 f> . D D 00 00 DD DD 00 00 00 00 -0 00 DD DD DD DD 00 00 00 00 00 a0 00 00 00 00 00 00 DD DD 00 00 00 00 00 00 00 00 00 00 00 00 0 -0 00 DD 00 00 00 DD DD 00 00 00 00 00 00 DD 00 00 00 00 00 00 00 DD 00 00 00 DD DD 00 00 00 00 00 00 DD 00 00 00 (s) - Day of severe ice and snow storms. 24 - Reading 24 hours after application. 4B Reading 48 hours after previous application but just before next application. Missed reading. * Panelist missed the scheduled patch application for personal reasons. Panelist was patched on the next scheduled application day, and the patch series extended until 9 induction applications were applied. ** Make-up patch application. (a) - Patch applied 1 day late. D Discontinued for.personal reasons. DuPont HLO 792-93 mpaviy Sanitized. Does not contain TSC/ BIOSBARCH, INCORPORATED - P.O. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 - (215) 739-4499 Project Number: 93-7949H E.I. Du Pont De Nemours & Company - H-20386, as supplied. Modified Draixe Repeated Insult Patch Test Study in Human Volunteers i ft-o0 o 3 n> S: 0 ss? <Na` p. wnoO> o3 nor oo 3 3sSsT* 9s> O Table 2 - Sunnary of Data Induction Phase 1 24 48 Tafcal Subjects: 120 120 Scads 2 24 48 120 120 3 24 48 120 120 4 24 48 120 120 5 24 48 120 120 6 Si.19 120 120 7 2 L it 12Q 120 8 24 48 1 2 & 120 9 21_U 120 020 10*4 21__ 1 1 17 I T 0 116 117 115 116 116 114 94 104 91 101 101 110 107 110 109 110 110 109 17 17 00 00 00 00 00 00 00 00 0000 14 00 00 00 00 00 00 00 00 0000 24 00 00 00 00 00 00 00 00 0 0 00 34 00 00 00 00 0 0' 0 0 00 00 0000 44 00 00 00 00 00 00 00 00 0 000 - 20 21 1 0 20 8 20 10 10 0 30 10 0 100 D 23 33 36 68 99 9 10 10 10 10 10 10 10 0 0 E lttU fiQ S lfi Original Virgin Site Site 24 48 31.11 120 120 120 120 107 105 00 00 00 00 00 107 105 00 00 00 00 00 02 13 13 02 13 13 Reading 24 hours after application. Reading 4> hours after previous application but just before next application. Missed reading. Discontinued for personal reasons. BXOSEARCH, INCORPORATED - P.O. BOX 8S98 - PHILADELPHIA, PENNSYLVANIA X9101 - (2&S) 739-4499 DuPont HU> 792-93 Project Number: 93-7949H DuPont HLO 792-93 A ppendix I E.I. Du Pont De Nemours le Modified Draize Repeated Insult Fetch Test Study in Human Volunteers Panelist Number 1 2 3 4 5 6 7 8 9 10 11 12 13 14 IS 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 S3 54 55 56 57 58 59 60 InMab W.L.B. E.R L.P. D.Z. j.B. EG. JR. N .E JR ET. J.S. P.M. P.H. D.L. V.M. CD. N .C PC. D.S. M.F. EG. D.M. K.B. S.L. EE J.E J.E R.D.B. CM ES. D.O. O.M. B.T. N.S. H.F. L.C. E.W. EC S.A. H.W. S.R. S.B. M.C. B.C. D.H. J.H. R.S. JI. w.w. L.W. M.H. G.S. C.S. D.B. EF. L.S. J.H. T.D. D.C. A.L. P^NBI^ffl1LJST Occupation A 2e*t 39 Unemployod H tjlever 29 Uneamtowd 30 52 HOflMOUfcW Tomatoes 39 Homemaker Asthma, taddU n, Animal Hair,Scasona 30 HomMMktf H iH w er 27 OWtWaehar M ao Ivy, Seasonal 41 Homemaker Hayfever 35 Hayfever 25 Hom naSw 45 Homemaker Damon, FenkOUn 31 Homemaker 34 Nona 33 Hommtker Gats - 32 M nlar 44 H ontnftktr Shflfish - 39 38 m i i m v 29 H oam sker fknfciBn Fmfcmtn, Seasonal, Hayfever 27 Hoommkcr 52 Honcnikflr Cab 27 HOflMBMte Freemm. Aspirin 32 Cuhicr - 49 School Aide Tomatoe 29 ! 37 1 *H**o-mcmi--n-efw-c-eii Soaaonal IMcOUn 19 Student - . 47 Unemployed 29 i Ilo ftw iffr taddU n 2 Homtmaktr Seasonal, Hayfever 34 1 Homematar 30 ! Homemaker 28 ' Homemaker Hayfever, Seaaonal - FenidlUn 29 ' Homemaker 46 i Homemaker Status Dogs,Hayfever,Ragweed,Sulfs 24 ^ Homemaker Asthma 19 1 d a * 40 i Homemaker 33 i Homemaker PoUen Statua Cab 38 : Homamaktr Hayfcver 42 Homemaker Dust 39 Check Cashier Dust Occasionally 2 1 Caehkr 43 Crossing Gueid - 38 : Scoatasy Animal Hair 46 : Machine Opento - 26 Driver H ayfem 29 : Homemaker JrluVCi 2 1 Student Dint, Asthma 38 ! hctoiy noik Statua 41 Homemaker 53 , Homemaker feflfcflHn - 44 i Cashier Tetanus 2 0 Student Cat Hair 45 Homemaker * 44 Homemaker - 34 : Homemaker - 35 Hayfever 44 E S f f i E . 19 Makes Lampshade ompany Sanitized. Does no! coniain TSCAC: - 23 Project Number: 93*7949H DuPont E.!. Du Pont De Nemours k Ompanjr Modified Draize Repeated Insult Pah* Test Study in Human Volunteers PANELISTLIST(conflnued) PineUtt* Number 61 62 63 6 65 66 67 66 69 70 71 72 73 74 75 76 77 78 7 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 11 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 Initial* K.H. C.S. J.K. T.S. S.S. A.W.N. H.H. C.C. V.G. P.J. M.F. JF. A.V. w.v. R.R. J.W. K.G. M.V. E.H. M.G. K.H. J.M.k. D.R. M.G. M.K. C.S. S.S. C.M. A.T. P.W. M.R. C.R. A.P. J.G. J.P. I.D. M.C. R.F. M.E.F. D.L. M.S. C.G. M.J. R.B. S.M. ML. I.G. C.U. J.N. J.J. I.W. M.P. R.B. A.B. A.E. D.B. S.S. C.A.D. S.B. M.A. Afll 41 37 25 38 38 46 54 6 21 37 42 46 20 41 29 24 42 34: 40 55 46 27! 28! 19 481 39! 35 24 18; 42 53i 37 41 35 43 : 31 50 18 48! 27 ! 19 : 18 36 35 ; 32 : 26 51 49 19 22 52 19 24 26 41 37 41 55 38 j 18 Occupation Bu Driver Teacher'* Aide U ntm pbytd 1f H am m lm hootN ot mmlrhit Honcowker Homemaker Homemaker Tree Surgeon Ummpbyd Hooitmater Homemaker Homemaker Supervisor Hom im ater Homemaker Homemaker smwfw Contraction Homemaker Homemaker ftesier Student Homemaker Homemaker Homemaker Avon Lady Unemployed y n n p lo jfid Homemaker Homcmater Student Cook Homemaker Student Student Homemaker Homemaker N ine's Aide Burger King Homemaker Homemaker Student Metalworker Homemaker Student Homemaker Rooter Homemaker Maintenance Unemployed Homemaker Homemaker Student Allergies Sinus Petdcfflin Duat Pollen Ragweed 79 1 Company Sanitized, Does not contain TSCA C Project Number: 93-7949H DuPont HU) 792-93 Appendix n E.I. Du Pont De Nemours & Company - H-20386 Modified Draize Repeated Insult Patch Test Study in Human Volunteers GRADING SCALE Human Patch Test Studies Reading 0 1+ 2+ 3+ 4+ negative suspicious slight erythema well defined erythema erythema with induration erythema with 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 developm ent. 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 elicit severe skin reactions after a number of exposures. Nevertheless, these reactions may not be considered incidents of sensitization since after 10-14 days of rest the skin recovers its original resistance to injury by the substance. For the lade 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 hi 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 Foods, 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 TSC Cf. UIOSEARCH, INCORPORATED P.O. BOX 959$ PHILADELPHIA, PENNSYLVANIA 19101