Document nkz4q7Jp1QL7BmDJ2ZkOjaxga

FOR DU PONT USE ONLY y./ .... . ;_ T .. _.. . .. "'I!-' .>||J l J i B ( f l W P f ! ^ l ! l l ^ | AR226-2949 Du Pont HLO 379-90 Study Title son Human Pateti; t of * tjest Item) {Control Item) Study Completed On I July 11, 1990 iI Contracting Laboratory Biosearch, Inc. 3408-50 B Street Philadejphia, Pennsylvania 19134 for E. I. du [font de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box 50 Newark, Delaware 19714 i- Laboratory Project ID Haskell Laboratory Report No. 379-90 ! ! ; Company Sanded. Does ^ Material Tested; Medical Research No.: Haskell No.: Haskell Test Code: Biosearch Project No.; Physical Form: Synonyms : I GENERAL INFORMATION I '' -iI Du Pont HLO 379-90 Test Material 90-7004H White fabric Other Codes: Material Tested: Medical Research No.: Haskell No.; Haskell Test Code: Biosearch Project Ho.: Physical Form: Synonyms : 18,331 te a 90-7004H White fabric Company Sanitized. Does not contain TSCA CBl Sponsor: Materials Submitted by: Study Initiated - Completed In-Life Phase Initiated - Completed: Distribution: Fibers department de Nemours and Company Wilmington, Delaware rrberstrepertment E. I. du Font de Nemours and Company Chambers Works Deepwater, New Jersey 5/7/90 - 7// 9 0 5/7/90 - 6/20/90 [I Company Sanitized. Does not contain TSCA CIS CENTRAL RESEARCH AND DEVELOPMENT DEPARTMENT HASKELL LABORATORY FOR TOXICOLOGY AND INDUSTRIAL MEDICINE] Du Pont HLO 379-90 July 11, 1990 Fibers Department Kinston Plant Kinston, North Care' na inn-Person Human Patch Test of ------- ------ ' ^ ( T e s t Item) |(Control Item) Attached is a report from Biosearch, Inc. (Biosearch, Inc., Project No. 90-7004H). Included in the report are patch test methods,-results and conclusions. No dermal irritation was observed at anytimeJn_any_of th^lOl active participants when tested w i t h ^ -- f M ^ ^ ^ M ^ (Test ItenU or -------c------- -- ------------ Control Item). ihe results of Biosearch, Inc. are acceptable and indicatethaJ Nylon samples are neither skin irritants nor sensitizing agents under the conditions of testing. Dolores E. Malek, Ph.D. Research Toxicologist DEM/lmr/HL09.34 not contain TSCA GBl^ Company Sanitized. Does I 1 G.R. 2f 2 M.V.C. 26 H t p d i ^ e r . I 3 C.S. 45 Homemaker b 4 S.C. 43 R e^ tered N u rse S? 5 M.G. 58 Homemaker 6 V.F. 44 Homemaker 7 G.I. 33 Unknown 8 R.G. 63 Handyman 9 H.S. 57 Homemaker r 10 H.E.C. 36 Brick Pointer 11 E.M. 33 Homemaker 12 C.S.L. 57 Homemaker 13 A.G. 32 Homemaker House dust 14 J.A. 33 Mechanic Penicillin 15 I.J. 50 Hor'maker 16 R.S. 42 Unemployed 17 D.R. 26 Sub-Teacher Aide 18 K.L. 21 Homemaker 19 C.H.E. 53 Homemaker 20 K.M. 29 Homemaker 21 P.H. 60 Homemaker 22 M.A. 60 Homemaker 23 M.C. 43 Homemaker 24 M.S. 33 Homemaker 25 A.B. 64 Homemaker 26 T.R. 38 Painter 27 L.G. 27 Homemaker Cats,Penicillin 28 K.T 21 Housewife 29 C.D. 44 Homemaker Fiberglass 30 W.L. 54 Unemployed 31 J.R. 64 Cleaning Man Hayfever 32 M.W. 60 I Tomemaker 33 D.H. 56 Homemaker 34 E.H. 58 | Grocery Clerk 35 D.V. 50 | Homemaker - 36 M.S. 45 Homemaker 37 D.N. 25 Unemployed 38 B.N. 32 Cashier 39 J.N. 37 \ Unemployed i 40 K.B. 35 I Nurse's Aide 41 D.R. 29 ! Homemaker Penicillin,Codeine 42 C.A.M. 40 Homemaker Starch 43 J.W. 20 Homemaker 44 M.M. 31 Factory Worker 45 J.B. 36 | Homemaker Asthma BIOSEARCH. INCORPORATED - P .b . BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 - (215) 739-5499 ! Company Sanitized. Does not contain TSCA CBl 46 C.A.D. 47 N.B. 48 D. A. 49 G.H. 50 51 52 53 54 55 56 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 85 86 87 88 89 >) 90 J.D.T. S.K. G.L. E. T. M.C. E.D. T-F M.A. P.A.N. M.M. J.M. J.W. J. J.H. S.R. K. M. D. F. E. S. W.S. J.L. D.G. M.L.S. R.C.G. J.F. D.B. A.M. C.H. M.F. J. G. M.B. W.W. P.D. A.M. P.M. M.M. C. C. D. M. K. W. V.A.O. D.W. M.B. F.P.M. '56 51 56 20 32 34 46 42 42 64 60 38 16 34 17 65 59 30 55 44 41 37 48 65 42 148 Dry Wall Installer Unemployed Unemployed Cafeteria Worker Homemaker Unemployed Homemaker Homemaker Homemaker Homemaker Homemaker Unemployed Homemaker Unknown Retired Homemaker Retired Cashier Homemaker Homemaker Housewife Homemaker Homemaker Homemaker Homemaker Homemaker Student Homemaker Student Retired Homemaker Security Ward Clerk Homemaker Homemaker Homemaker Registered Nurse Teacher's Aide Data Entry Unemployed Sulfa Drug Penicillin Dust Cats Aspirin,Sulfa Drugs I ' Company Sanittead. Does not <onta.il TSCA CM Ii IIi iI ii I BIOSEARCH, INCORPORATED!- P.O. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 - (215) 739^499 I Company Sanitized. Does not contain TSCA CE(i WJ BIOSEARCH, INCORPORATED P .O . BOX 8598 PHILADELPHIA, PENNSYLVANIA 19101 (215) 739-M99 Company Sanitized. Does not contain TSCA CQI BIOSEARCH INCORPORATED P.O. Box 8599$il,, Philadelphia, Pqiiiisylvrmia 19101 Tr((lephon: (215) 739-4499 Fax: (215) 423*9210 Pmjert Number: Testing Facility: Sponsor: 90-7004H Biosearch Incorporated 3408-50 "B" Street Philadelphiji, PA 19134 E.I. Du Porit De Nemours & Company P.O. Box 50, Elkton Road Newark, d 19714 I Test Article: H-18,330 Test Article Description: White material Test Article Received: Study Initiated: 05/04/90 05/17/90 Rhidy Completed: 06/20/90 Date of Report: Test: Subjects Object of Test: Method of Test: 06/21/90 Modified Draize Repeated Insult Patch Test Study in Human 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 the Association of Food and Drug Officials of the United States. The test involved the application of the test article to the upper arms of a group of 107 volunteer subjects. One hundred and one subjects completed the study. These subjects 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 subject was required to read, understand and sign an informed consent statement. The test article was tested as supplied. i Company Sanitized. Does not contain TSCA CD! Project Number: E.I. Du Pont De Modified Preise Method of Teat: Induction Phase 'tiji'vv,:.!/<5risL Iner-SH O a ^ ^ fe :iM of test artide was applied to hypoallergenic doth tape ^ # NI 08903>- Te patch remained in At theertd-^this , ^ ,.. was removed and the site was exandtied *S7c.--orin-gg. -of irritation was in aareccn:cc>oto.-errrddaaafnnocrcees yyrnttaiit the l^ p i^ # fo fmfyf f*esrert^nhV*dae*isxkrbvii.nn ssTii.tt-hoe-e--wu-s-na-ua-sb- *aajegcpmt,'sn wepxyeaarmem.imtnheaeda,n.. A patch w ar then applied to the same site as previously used. The second appU aiott was idenridd tp & e first and remained in place 24 hours This procedure was replaced on Mondays, Wednesdays and Fridays until a serill pf ten1'applications had been made. Patch applications made on Friday were" removed by the subject on Saturday. Ih e subjects^ examined the site for any dermal response and reported their observa ions prior to the next application. The same site continued to be used throughout the study. Challenge Phase After the 10Ilh application, a rest period of approximately 2 - - weeks elapsed afterJ which a Challenge application was applied in the same manner and to the same sites described above. A duplicate challenge application Was also applied in the same manner to a virgin site (previously untreated). The challenge application was removed after 24 hours and th - sites were examined for signs of irritation or sensitization, Follow up es:xaminations were conducted at 48 hours after the challenge application. The subjects nvolved in this study ranged in age from 16 to 65 years of age. Results: See accompanying table, summary and appendix. BIOSEARCH, INCORPO11ATEO P.O . BOX 598 - PHILADELPHIA. PENNSYLVANIA 19101 Company Sanitized, Does not pont^lr) TQA CB* Project Numter pmtM W Jbam E.I. Du Pont De NeinQHfS & Modified Draize R e p e ^ e d in s p Subjects >V` Conclusion: , '< . -~r.'.If/ ; F r w 'if c '1 M l l j ^ y w escribed ab vfcrit i dije Le test arride is most likely iioM ^ most likely not a fatiguing agent T K a t ^ t ^ l ^ ^ ^ ^ i t i z i n g agent. ':.wIt;ifi'>V.5*'^*v-t. .-L''ifzfiliJ:V. '^m ~W M m ' ',35 Signatures: Submitted by ^ ierickUr>ach, ^ Consultant I ermatologist land Affi imi Study Directo: Raymond Medical Din Karl L. Gabriel, V.M.D., Ph.D. President BIOSEARCH, INCORPORAk'TCD. ,o . Does not contain TSCA CB3 Project Number; 90-7004H E .I. Du Pont De Nemours & Company - H-18,330, as supplied. Modified Draize Repeated In s u lt Patch Test Study in Human Subjects Table 1 Subject Number 1 24l_48 2 24_48 3 24 48 4 24 48 Induction Phase 56 24 40 24 48 7 24 M 8 24 48 9 24 M 10 24_48 Challenge Original Virgin Site Site 24 48 24 48 1 00 00 00 00 00 0 0 00 00 2 00 00 00 00 00 00 -0 00 3 4 00 00 00 00 00 00 00 0n 00 00 00 00 00 00 00 00 5 00 00 00 00 00 0 0 00 00 6 ~ 0 on - - IT" i r 0 ----(T 0 0 0 0 0 0 0 0 u 7 00 00 00 00 00 0 0 00 00 8 00 00 00 00 00 00 00 0G 9 00 00 00 00 00 0 0 00 00 10 0 0 0 0 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 0 0 0 0 12 0 0 0 0 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 0 0 0 0 14 OC; *303oS) Oo*auiA5.n? 15 16 17 18 19 20 21 22 23 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 (toroi)? 24 25 00 00 00 00 00 00 00 00 o3 24 = Reading 24 hours a f te r ap p licatio n 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 0 00 00 00 00 -0 00 00 00 -0 00 00 00 00 00 00 00 0* 00 00 00 00 oo 48 = Reading 48 hours a f te r previous a p p licatio n but ju s t before next ap p licatio n - = Not graded a> 3' " Missed application D = Discontinued; subject withdrew from study fo r personal reasons. 00 00 00 00 00 -0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 -0 00 00 00 00 00 00 00 00 00 0 "0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DT D 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 00 00 00 00 00 TT D 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 & o BIOSEARCH, INCORPORATED - P.0. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 - (215) 739-4499 Du P o n t HLO 3 79 -9 0 Page 4 of 9 Project Number 90-7004H E.l. Du Pont De NemourB & Company - H-18,330, as supplied. Modified Draize Repeated Insult Patch Test Study in Human Subjects Table 1 (continued) Induction Pha-e Subject Number 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 1 24 48 2 2k- 48 3 24 48 00 00 00 00 00 00 00 00 00 00 --0---6--- -- 0-o-. 00 00 00 00 00 0r 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 V-- u 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 4 24 48 5 24 48 6 24 48 00 00 00 00 00 0n 00 00 00 00 -- 0---- 0-- -- 0---- u-- 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 00 00 00 00 00 00 00 00 00 00 00 00 00 7 24 48 00 00 00 00 0 n 0A 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 0* 00 00 -0 6 24 48 9 ?4 48 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 00 00 -* 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 24 " Reading 24 hours after application 48 =* Reading 48 hours after previous application but just before next application - = Not graded * <= Missed application D - Discontinued; subject withdrew from study for personal reasons. 10 24 48 00 00 00 00 00 -0- -O00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 Challenge Oi^ginal Virgin Site Site 24 48 24 48 DD 00 00 00 00 --- -000 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 D 0 0 0 0 -0--0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 Company Sanitized, Dges not contai^ TC(\BI BIOSEARCH, INCORPORATED - P.0. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 - (215) 739-4499 Protect Number; 90-7004H E.I. Du Pont De Nemours & Company - H-18,330, as supplied. Modified Draize Repeated Insult Patch Test Study in Human Subjects Table 1 (continued) Induction Phase Subject Number 51 52 53 54 55 56.... 57 58 59 60 61 62 63 64 65 C6 67 68 69 70 71 72 73 74 75 1 24 48 00 00 00 00 00 nn 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 n - nV" 00 00 00 00 00 00 00 -0 00 00 00 00 00 00 00 00 00 00 00 3 24 48 00 00 00 00 00 AA 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 4 2Jl - 48 00 00 00 00 00 AA 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 -0 00 5 24 48 00 00 01 00 -0 AA 00 00 00 00 00 00 00 00 -0 00 00 00 00 00 00 00 00 00 00 6 24 48 00 00 00 00 00 A A. 00 00 00 00 00 00 00 00 .0 0 00 00 00 00 00 00 00 00 00 00 7 24_48 _0 00 00 00 00 -- o--8-- 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 8 24 48 00 00 00 00 00 u-- ir 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 9 24 M 00 00 00 00 00 0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 24 ** Reading 24 hours after application 48 = Reading 48 hours after previous application but just before next application - = Not graded D = Discontinued; subject withdrew from study for personal reasons. 10 AS 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 Challenge Original Virgin Site Site 21. 48 24 M DD 00 00 00 00 uu 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 Du Pont HLO 379-90 Page 6 of 9 Company Sanitized. Does not contain TSCA CBI BIOSEARCH, INCORPORATED - P.0. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 (215) 739-4499 E.I. Du Pont De Nemours & Company - H-18,330, as supplied. Modified Draize Repeated Insult Patch Test Study in Human Subjects Table 1 (continued) Induction Phase Subject Number 76 77 78 79 80 -- 8i 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 1 24 48 00 00 00 00 00 O -0 00 00 00 00 00 00 00 00 00 00 0 00 00 0D 00 00 00 0 00 2 2L.i l 3 21_ 48 4 24 il 5 li_il 00 00 00 00 00 00 00 0 00 00 00 00 00 00 00 00 00 00 00 00 0 --0 - -----0- - 0 -- -- -0-- 0 -----o -0-- 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 *0 00 00 00 00 00 00 00 00 00 00 00 DD DD DD DD 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 _0 00 00 00 6 2i_il 7 2i_i l 00 0n 0 00 00 _ o _ o --- 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 00 00 00 00 00 00 0-- 0 00 00 00 00 00 -0 00 00 00 00 00 00 00 DD 00 00 00 00 00 8 2i_il 00 00 00 00 00 o.- O 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 00 9 !i_il 10 2i_il 00 00 00 00 00 00 00 00 00 00 - 0 -0-.... -- O- IL 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 0- DD DD 00 00 00 00 00 00 00 00 00 0- 24 - Reading 24 hours after application 48 *= Reading 48 hours after previous application but just before next application - = Not graded D = Discontinued; subject withdrew from study for personal reasons. Challenge Original Virgin Site Site |4_ 4 ?4 48 00 00 00 00 00 00 00 00 00 00 .... - 0 _ ...H-- ____ 0 __Ol 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 DD DD 00 00 00 00 00 00 00 00 00 00 Du P o n t HLO 3 79 -9 0 Page 7 of 9 Company Sanitized. Does not contain TSCA rni BIOSEARCH. INCORPORATED - P.0. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 - (215) 739-4499 Protect Number: 90-7004H E.I. Du Pont De Nemours & Company - H-lfl,330, as supplied. Modified Draize Repeated Insult Patch Test Study in Human Subjects Subject Number 101 102 103 104 105 106 107 1 24 .48 00 00 00 00 00 00 00 2 24_ 48 00 00 00 00 00 00 0O 3 I L 48 00 00 00 00 00 00 00 4 24 48 0 00 00 00 00 00 00 Table 1 (continued) Induction Phase 5 24 48 6 24 48 78 24 48 24 48 00 -0 00 00 00 00 00 00 00 00 00 00 00 0O 0 0 00 0 0 00 0 0 00 0 0 00 0 0 00 0 0 -0 0 0 00 9 24 48 00 00 00 00 00 00 00 10 1L. 48 0 00 00 00 00 00 00 Challenge Original Virgin Site Site 24 48 24 48 00 00 00 00 00 00 O 00 00 00 00 00 00 O' O Du P o n t HLO 3 7 9-9 0 Page 8 of 9 Company Sanitized, Does not contain TSCa C 24 - Reading 24 hours after application 48 = Reading 48 hours after previous application but just before next application - = Not graded D - Discontinued; subject withdrew from study for personal reasons. BIOSEARCH, INCORPORATED - P.0. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 - (215) 739-4499 p ro je c t Numberi 90-7004H E.I. Du Pont De Nemours & Company - H-18,330, 86 supplied. Modified Draize Repeated Insult Patch Test Study in Human Subjects Summary of Table 1 1 24 48 2 24 48 34 24 48 24 48 5 24 48 6 24 48 78 9 24 48 24 48 24 48 10 24 48 Challenge Original Virgin Site Site 24 48 24 48 Total Subiectst 107 107 107 107 107 107 107 107 107 107 107 107 107 107 107 107 107 107 107 107 107 107 107 107 Readings tr ` * a It)5 106-- 102 lOtr'208 206-- 104 106 -103-108 20 40 0 0 2 0 3 0 0 0 00 00 0 0 00 0 1 11 111 111 106-- 106 100 -105- 104 104 - 103 105 00 00 60 20 0 10 2 20 00 111 111 22 105 102 00 03 22 101102 00 00 66 101 101____ 00 00 66 Du P o n t HLO 3 7 9 -9 0 Page 9 of 9 Company Sanitized, Does not contain TSCA CB 24 = Reading 24 hours after application ,. ,, 48 = Reading 48 hours after previous application but just before next application - = Not graded * - Missed application D *= Discontinued; subject vithdrev from study for personal reasons* BIOSEARCH, INCORPORATED - P.0. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 - (215) 739 4499 Projet* Number: 90-7004H Du P o n t E.I. Du Pont De Nemours & Cordpany - H-18,330 Modified Draize Repeated Insult Patch Test Study in Human Subjects HLO 3 7 9 -9 0 Appendix GRADING SCALE Human Patch Test Studies Reading 0 1+ 2+ 3+ 4+ Interpretation nejgative sufepidous 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 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 elicit severe skin reactions after a nuhnber 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 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 has lost significant normal physiological function, m s phenomenon consists of a subtle change in which the skin no longer exhibits its onginal 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. ; I I BIOSEARCH. INCORPORATED - P.O. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 Company Sanitized. Does not contain TSCA CBS Project Number: Testing Facility: Sponsor: Test Article: Test Article Description: Test Article Received: Study Initiated: Date of Report: Test: Subjects Object of Test: Method of Test: iasfaifcJ A T ^ n " * Ht<5 lvania 19101 'i W<f/|J V;1 Bioseardi fogpprted 3408,19'fB" Street ' Philadeijhia, PA 19134 -f E.I. Du Pont De Nemours Company P.Q. Box 50, Elkton Road "" Newark, DE 19714 H,18,331 /|j .(1./; Si ..I I 3 White material 05/04/90 05/07/90 Study Completed: 06/20/90 06/21/90 Modified Draize Repeated Insult Patch Test Study in Human To determiniie the irritating, fatiguing and sensitizing properties of the test a *ide. 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 the Assodation of Food and Drug Offidals of the United States. The test involved the application of the test artide to the upper arms of aj group of 107 volunteer subjects- One hundred and one subjects completed the study. These subjects were all determined to be in goi d general health and free of any visible skin disease or anomaly n the area to be patched. Each subject was required to read, unde:rstand and sign an informed consent statement. The test a rtide was tested as supplied. I Company Sanitized. Does not contain TSCA CBI I  M e t h o d of Tesi: Induction Phase oneitich sgaiue s t W R of test article was applied to (Johnson p l a c e 5"'' t'- 08903)- ^ P8tch remamed m Challenge Phase At the end removed " examined for any Sconng of " accordance with the ^ $ i f e ? # n d i x . The subject* were then rested for a 2 4 i o w p e i i ? d ^ ^ e akin Slte wa? a6?ta A patch was then applied to t^ 's a jg * site as Previously ujed. The second appUcation was ideiStiicnl fo $ first and remained in place 24 hours. This procedure waif repeated |>n Mondays, Wednesdays and Fridays until a series of ten apFlhpetions had been made. Patch applications made on Friday were removed by the subject on Saturday. The subjects examined the site for ajiy dermal response and reported their observations prior to the next application. The same site continued to be used throughout the * ' After the 10th application, a rest period of approximately 2 * 3 weeks elapsed after w hich a challenge pplijation was applied in the same maimer and to the same sites described above. A dupticate challenge application was also applied in the same manner to a virgin site (previously uriitreated). The chaUenge application was removed after 24 hours and the ites were examined for signs of irritation or sensitization. FoUow up examLinations were conducted at 48 hours after the challenge application. The subjects inv olved in this study ranged l . age from 16 to 65 years of age. Results: See accompanying table, summary and appendix. V 3IOSEARCH, INCORPORATED P.O. BOX 8 5 - PHILADELPHIA, PENNSYLVANIA 19101 Company Sanitized. Does not contain TSCA CBS Prnjprt Number: 90-7004H Du P o n t HLO 379-90 Page 3 of 9 E.I. Du Pont De Nemours 4c Company H-18,331 Modified Draize Repeated Insult Patch Test Study in Human Subjects Conclusion: From t e Fkely n o t. t e g t e g agent. The test article t most likely not a sensitizing agent. Signatures: Submitted by Bibsearch, Incorporated: ^ A / i d / A n / i/ & t/M' ' Roderick Urbath/M.D. Consultant Dermatologist Study Director Raymond Mark, M.D. Medical Director Karl L. Gabriel, V.M.D., Ph.D. President Company Sanitized. Does not contain TSCA CB1 A PENNSYLVANIA 19101 BIOSEARCH, INCORPORATED - P O . BOX E59S - PHILADELPHIA. m Prr^jpp^ Number; 90-7004H E.I. Du Pont De Nemours & Company - H-1B,331, as supplied. Modified Draize Repeated Insult Patch Test Study in Human Subjects Table 1 T n r i u r - t l o n Phase Subject Number 1 23_ 48 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 ... 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 2 23_38 00 00 00 00 00 0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 3 24-48 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 0 0 00 00 00 00 00 00 00 00 00 4 23- 4B 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 5 23_4B 0* 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 6 23_38 00 00 00 00 00 0 ir 00 00 00 00 00 00 00 00 00 00 0 00 00 00 00 00 00 00 00 7 23-48 00 -0 00 00 00 00 00 00 00 00 0 00 00 00 00 00 00 00 00 00 -0 00 00 00 -0 8 23_38 00 00 00 00 00 0"-o~ 00 00 00 00 00 00 00 00 00 00 00 00 00 00 0* 00 00 00 00 9 23 .38 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 0 00 00 00 00 24 - Reading 24 hours after application 48 = Reading 48 hours after previous application but just before next application - = Not graded * = Missed application D * Discontinued; subject withdrew from study for personal reasons. 10 2.4 A& 00 00 00 00 00 0 -0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 Challenge Original Virgin Site Site 24 48 23-48 0 0 0 0 0 -D-~B~ 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 .e- Du P o n t HLO 3 7 9 -9 0 Company Sanitized. Does not contajnJSgAilBl BIOSEARCH, INCORPORATED - P.O. BOX 8598 PHILADELPHIA, PENNSYLVANIA 19X01 - (215) 739-4499 90-7004H 1.I. Du Font De Nemours 6 Company - H-10,331, as supplied. Modified Draine Repeated Insult Patch Test Study in Human Subjects Table 1 (continued) Subject Number 1 2k-kB 2 2k-kB 3 2k-- M 4 2k-- kB. Induction Phase 5 2k-M 6 2k-- 48 7 2k-M 8 2k-kB 9 2k-M 10 2k-kB Challenge Original Virgin Site Site 2k-M 2k-k B 26 27 28 29 30 -31 32 33 34 35 36 37 38 39 40 ? *1 1 42 : 43 44 ) 45 46 47 48 49 1 50 00 00 00 00 00 00 00 00 00 00 O- --o- --- 0-- -0-- 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 00 00 00 00 00 00 00 00 00 *Q --- o-- 0-- ---0- -0-- -- 4)---0- 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 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 _0 ~~0-- -- 00 00 0 00 00 00 00 00 00 00 00 00 00 00 00 0* 00 00 0 00 00 00 00 00 a _a._. - 00 00 00 00 00 00 00 00 00 00 00 00 00 00 0_ 0 00 00 00 00 00 00 00 00 A. 0-.-00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 DD 00 '0 0 00 00 00 00 00 00 .0. ... .0.. A. 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 DD DD 00 00 00 00 00 00 DD 00 00 00 00 . -JO__0.. 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 24 = Reading 24 hours after application 48 * Reading 48 hours after previous application but just before next application - = Not graded * Missed application D Discontinued; subject withdrew from study for personal reasons. o-->i oCD BIOSEARCH, INCORPORATED - P.O. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 - (215) 739-4499 Du P o n t HLO 379-90 Page 5 of 9 Company Sanitized. Does not contain 90-7004H E.I. Du Pont De Nemours & Company - H-18,331, as supplied. Modified Drnize Repeated Insult Patch Test Study in Human Subjects Table 1 (continued) Induction Phase Subject Number 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 1 24_Afl 00 00 00 00 00 00 0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 2 24_Aft 3 24 Aft 4 24_Afl 5 24 48 6 24 _4fl 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 0 0 .........ft.. ft. . . . . . f t . . - f t ___ - -XL -ft -. ft-- 0 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 -0 00 00 00 00 00 00 00 00 00 00 00 00 00 -0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 o' 0 00 00 00 00 00 00 00 00 00 -0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 7 24, 48 B 24-Afl 9 24_ifl _0 00 0 00 00 0 00 00 0 00 00 0 0 0-- 0 0 0 ----0- 0 0-- ------- o0 00 00 0 00 00 0 00 00 0 00 00 0 00 00 0 00 00 0 00 00 0 00 00 0 00 00 0 00 00 0 00 00 0 00 00 0 00 00 0 00 00 0 00 00 0 00 00 0 00 00 0 00 00 0 00 00 0 0 0 0 0 0 a- 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 10 24_M 00 00 00 00 00 -.-ft 0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 2A - Reading 24 hours after application - ~N!!tflg d e d a hUrS Bfter previous aPPlication but just before next application ' -n = Discontinued; subject withdrew from study for personal reasons. Challenge Original Virgin Site Site 2A..4S 24 4S DD 00 00 00 00 0 0--00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 tr cr 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 Du Pont HLO 379-90 Page 6 of 9 Company Sanitized. Does not contain TS/^qj DIOSEARCH, INCORPORATED - P.0. BOX B59B - PHILADELPHIA, PENNSYLVANIA 19101 (215) 739-4499 Du P o n t HLO 379-90 Page 7 of 9 SI r' 90-7004H E.I. Du Pont De Nemours & Company - H-18,331, as supplied. Modified Draize Repeated Insult Patch Test Study in Human Subjects Tablf' 1 (continued) Tnrinr.t-.ion Phase Subject Number 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 1 2k-- 4B 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 -0 00 00 0D 00 00 00 -0 00 2 Ik-ifl 00 00 00 00 00 0 n 0c 00 00 00 00 00 00 00 00 00 0 00 00 DD 00 00 00 00 -0 3 Ik-M 4 24 48 5 Ik- 48 00 00 00 00 00 0 "0-- 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 00 00 0n 00 00 00 00 00 00 00 00 ---tr-- cr - -- 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 00 00 DD 00 00 00 DD 00 00 00 00 00 00 00 6 Zk-kB. 00 00 00 00 00 -o- -o00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 00 7 24 48 00 00 00 00 00 00 00 00 00 00 0 00 00 00 00 00 00 00 DD 00 00 00 00 00 8 Ik - 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 DD 00 00 00 00 00 9 I k - k 10 24 . M 00 00 00 00 00 00 00 00 00 00 n ~0- n... Q... 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 0- DD 00 00 00 DD 00 00 00 00 00 00 0- 24 = Reading 24 hours after application 48 = Reading 48 hours after previous application but just before next application - = Not graded D * Discontinued; subject withdrew from study for personal reasons. Challenge Original Virgin Site Site 2 k - 24 48 00 00 00 00 00 00 00 00 . 00 00 n .. _o. n. 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 DD DD 00 00 00 00 00 00 00 00 00 00 BIOSEARCH, INCORPORATED > P.O. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 - (215) 739-4499 Project NumberI 90-7004H l.I. Du Pont De Nemours & Company - H-1B.331, as supplied. Modified Draize Repeated Insult Patch Test Study in Human Subjects Subject Miimhpr 101 102 103 104 105 106 107 1 2A_M 00 00 00 00 00 00 00 2 Ik -M 00 00 00 00 00 00 0 0' 3 2 k 48 00 00 00 00 00 00 0 "0 4 I k .M -0 00 00 00 00 00 0r Table 1 (continued) Induction Phase 5 24 48 00 -3 00 00 00 00 00 6 2 k -k 00 00 00 00 00 00 00 7 24 48 00 00 00 00 00 00 "00 8 I k .M 00 00 00 00 00 0 00 9 2 k -M 00 00 00 00 00 00 00 Challenge Original Virgin 10 Site Site 2k. Ik .k& 2 k .M 0 0 0 0 0 .. O 0 0 00 00 00 00 0. ..... 00 0 0 0 0 0 Q. 0 00 00 00 00 00 SX.. 00 Du P o n t H L O 379-90 Page 8 of 9 Company Sanitized, 24 " Reading 24 hours after application -8""NotBgraded8 hUrS aft6r previous application but just before next application o <CnD D = Discontinued; subject withdrew from study for personal reasons. o3 3oo fi) 5' o0) D BIOSEARCH, INCORPORATED - P.0. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 - (215) 739-4499 !'i . i : 1' Project Numberl 90-7004H E.I. Du Pont De Nemours & Company - H-18,331, as supplied. Modified Draize Repeated Insult Patch Test Study in Human Subjects Summary of Table 1 Induction Phase 1 24 _4 IfiLal Subjects ; 107 107 Readings 2 it-48 107 107 3 4.-46 107 107 4 4 .48 107 107 5 2.4..48 107 107 16 2Jl Jtfl 107 107 7 24. 48 107 107 8 24-48 107 107 9 24. ,48 107 107 10 24-48 107 107 0 105 106 102 106 - I06~I06 104 T 0 " 103 ro r 106 106 T O O 1 0 5 " T 4 104 103 105 105 102 - 20 40 00 20 30 00 60 20 20 00 00 00 00 00 00 00 01 02 00 03 D 01 11 11 11 11 11 11 11 22 22 Challenge Original Virgin Site Site 24.. 48 2.4,.48 107 107 107 107 loi Toi 00 00 66 T l Toi" 00 00 66 Du P o n t HLO 379-90 Page 9 of 9 Company Sanitized. Does no! contain TSCA CBf 2 = Reading 24 hours after application -8=*Notagraded8 hUrS aft6r previous "PPiication but just before next application * * Missed application D => Discontinued; subject withdrew from study for personal reasons. BIOSEARCH, INCORPORATED - P.O. BOX 8598 - PHILADELPHIA, PENNSYLVANIA 19101 - (215) 739-4499 Project Number: 90-7004H Du P o n t HLO 3 7 9 -9 0 Appendix E.I. Du Pont De Nemours & Compja:ny-H-18,331 Modified Draize Repeated Insult Pi'tch Test Study in Human Subjects GRADING SCALE Human Patch Test Studies Reading 0 1+ 2+ 3+ 4+ Interpretation i negative suspicious slight erythema well defined erythema erythema with induration uythiema with ulceration DEFINITIONS* Sensitization is a phenomenon which manifests itself by local effects on either skin or mucous membranes. It differs frofri 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 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 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 has 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 Sanitized. Does not contain TSCA CBI BIOSEARCH, INCORPORATED - P.O. BOX 859B - PHILADELPHIA, PENNSYLVANIA 19101