Document rxykX81j5gMwKOy9Gqv7eG8xq

, FOR DU PONT USE ONLY -'ril... AR226-2932 Du Pont HLO 408-87 Study Title Test) and "(Test) Author John E. Henry Study Completed On July 30, 1987 Performing Laboratory Haskell E. I. du Pont de Nemours and Company, Inc. Laboratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box 50 Newark, f)e1 aware 19714 Medical Research No. Laboratory Project ID Haskell Laboratory Report No. HLO 408-87 Page 1 of 2 BMMpany SonMxad. Doe no qqrrtatn T^CA <W\ CENTRAL RESEARCH AND DEVELOPMENT DEPARTMENT HASKELL LABORATDRY FOR TOXICOLOGY AND INDUSTRIAL MEDICINE CHEMICALS AND PIGMENTS DEPARTMENT TECH LABORATORY July 30, 1987 Attached is report HLO 408-87 (Biosearch, Inc., Project Number 87-5670H), Included in the reports are patch-test methods, results and conclusions. The test materials were judged to be neither pMmary skin irritants nor sensitizing agents when tested by a repeated-insult patch test. The conclusions of Biosearch, Inc. are acceptable And dermatitis Js expected from the normal intended t that no U^.i. ii^Y J. E. HENRY TECHNOLOGIST JEH:smk:HL07.49 Attachment 'SoiHpenf SanRteed. 'Doss ncAoontefe TSC QBS, 1 \ --L B ^r pro ject Ninb<: E-1 . du Pont de Nod Ifled Ora Ize 87-S 670B ULO- 40^'n Nemou r8 C:ompa ny. Inc. (Refer to your letter of 05/12/87) Repea fed Irlault Hatch Test Study in Human Subjects Sub ject NUB icr In itials Sub4ect List Sex Age Complexion Allergies ^|3| S^ 1 2 ^ ^ 4 5 6 7 8 9 10 11 12 13 11 15 16 17 18 19 20 21 ' 22 23 24 t.A. F"..A. F 58 Medium P 68 Pair V/.A. F 57 Fair f\t.A. F 65 Medium L..B. F 48 Pa i r R .M.B. F 28 Medium M .B. F 28 Fair J .B. F 44 Fair F.M.B. M 28 Medium R .P. T .B. S .B. J .B. M 46 Mediua M 57 Medium F 49 Medium F 54 Pair D .M.B. P 56 Medium M .B. F 31 Pair K .C. F 35 Me-liura D .C. F 30 Fair J .A.C. F 25 Fair C .C. F 41 Fair C .D. F 19 Medium B .n. F 17 Medium I) .0. F 49 Fair K .D. F 27 Fair K . I . D. F 33 Medium cats 25 K .D. F 43 Pair- 26 A M.I). F 29 Fair 27 M D. M 31 Medium 28 M K. F '14 Med i urn 29 B E. F 64 Fair 30 R R. F 60 Medium 31 J M.F. M 33 Medium 32 L P. F 28 Paii 33 S F. F 39 Fair 34 J. G. P 28 Fair 35 S G. F 18 Fair 36 B. H. F 22 Fair 37 D. H. F 17 Medium 38 E. H. F 41 Fair 39 E. A.H. F 15 Medium 40 M. H. F 49 Medium 41 S. H. F 32 Medium 42 J. H. F 43 Fair bee stings 43 D. H. F 31 Medium 44 I. I. F 57 Medium 45 C. J. F 35 Pair 46 A. K. F 54 Pair nylon 47 C. K. F 36 Fair 48 B. K. F 57 Fair 4S K. L. P 26 Fair \ 50 M.L. F 28 Medium / 51 S. L. P 32 Fair dust 52 D. L. P 16 P.-a-ir BIOSEARCHi1NCORPOBAT- EPP.O. BOX659B - PHILADELPHIA. PENNSYLVANIA19101 - (215) 17)-kW Project 1NUBber: E.I. du 'Pant de Modified Draize Ne8m7o-5u 6raTOHft Ciompany , Inc. (Refiir to your letter of 05/1Z/87) Repea fed In;Bult Piatch Teat Sltudy in Human Subjects iSub.lec t List (coniLinued) Subject Number Initials Sex Age Complexion Allergies 53 54 55 56 57 58 i^jQ*7 60 61 CbOe 63 64 65 C0C0 67 C0Q0 69 70 71 72 73 7.1 75 76 77 78 79 80 81 82 83 84 85 86 0m f O0Q0 OQOff 90 91 92 93 94 q!7^J 96 97 98 99 100 101 102 103 G.L. A.L. P.M. R.A.M. M.Mw. M.M. R.M. E.M. A.E.M. EM. CT . J.M. R.M. H.M. J.M. M.M. P.M. J.P.M. J.N. M.N. n.o. N.O. M.P. J.L.P. C.G.P. D.P. R.P. S.P. J.Q. R R. S.R. M.R. J.R. K.R. A.R. L.R. U.S. L.S. C.S. M.S. M.S. M.A.S. R.S. H.S. M.S. K.T. C.T. B.T. A.V. H.W. D.W. S.Z. F 35 Pair F 49 Pair P 33 Mediun F 35 NediuB F 17 Mediui F 18 Pair F 42 Medium F 30 Pair V 53 Pair F 64 Medlua V 54 Fair F 46 Medium F 43 Medium r 61 Medium F 44 Medium F 54 Fair M 53 Medium F 37 Fair M 17 Fair F 2B Fair F 52 Fair F 25 Med i urn M 50 Med i urn M 53 Fair F 26 Fair M 27 Med i urn F 16 Pair F 19 Medium F 25 Medium F 52 Med i urn F 21 Medium M 61 Fair F 42 Med i UB F 29 Medium F 39 Pair F 64 Fair F 35 Medium F 36 Fair F 42 Medium F 29 Medium F 30 Pair F 51 Medium F 5-1 Ned i urn F 48 Medium F 17 Fair F 25 Pair F 33 Fair M 66 Medium M 55 Fair F 28 Medium F 34 Pair - ~ " penicillin " penicil1 in - pen id 11 in ~ ' ~ Indocine " penicili in pcnici]1 in poison ivy ~ hayfever penici11 in penicillin ~ seafood ^ ~ ^ ^" ^ &v -A-^* B10SEARCH,INCORPORAT-EDP.O. BOX B5TO - PhlLAOELPHIA,PENNSYLVANI1A9101 - (215) 739-UW /// BI03BARCH INCOR.POR.ATEO /// /// P.O. Box 8598. Philadelphia. P--MyIvania 19101 /////A\\ Telephone: (215) 739-4499 ////// /// /// \\\/// Project Number: 87-?o70H Testing Facility: Blosearch Incorporated 340B-10 "B" Street Philadelphia. PA 19134 Sponsor: F..I. du Pont de NeMorrs & Company, Inc. Haskell Laboratories P.O. Box 50, Elkton Road Newark. DE 19714 Test Article: 16.759 Test Articis Description: Test Article Received: Study Initiated; Date of Report: Blue fabric 05/14/87 05/27/87 07/06/87 Study Completed: 07/02/87 Test: Modified Draize Repeated Insult c'atch Test Study in Human Subjects Object of Test: Method of Tcit: To determine the Irritating, fatiguing and aenii'ti?.ing properties of the test article. The method employed in carrying out this test was similar to that described in "Appraisal "f the Safety of Chemicals in Foods, Drugs and Cosmetics" by J.H. Draize and published by the Association of Food and Drug Ofiiclals of the united States. The test Involved the application of the test article to the upper arms of a group of 103 volunteer Cauca sian subjects. These subjects were all determined to be in generally good health, 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 statenenc. The '-.est article was tested as supplied. Project Number: 87-5670H E.I. du Font de Neour & Company, Inc. - 16,759 Modified Draice Repeated Insult Patch Test Study In Human Subjecf Method of Teat; (continued) Results: Approximately a one Inch aquare portion of test article was applied to the appropriate akin ite and covered with 2" ;xra:icel hypo-allergenic cloth tape (Johnaon & Johnsor. New Brunswiek, N..T. 08903). The patch remained in -riace for 24 hours. At the end of this period, the patch was removed and the site was examined for any dermal response. Scor ing of irritation was in accordance with the scale in the Appendix. The subjects were then rested for a 24 hour period after which the skin site was again examined. A pate- was then applied to the same site as previously us^d. The second application was identical to the i.rst and remained in place 24 hours. This procedure was repeated on alternate day untfl a soles of ten applications had been made. The same site continued to ~,e used throughout the study period as long as no irritation or only minimal irritation (1+) was seen ar-.-r each 24 hour rest period. If greater irritatio- (2+ or more) was noted then the subject was either rested or the contact ulte was changed at the discretion ot the investigator. Approximately a .. co 3 week rest period then elapsed after which a cha'i'.enge application was applied in the same manner and tc the same sites described above. A duplicate challefi- application was also applied in the same manner 1.0 a virgin site (previously untreated) on lie other arm. The challenge application was r-eoved after 24 hours and the sites were examined --or signs of irritation or ""nsi t'zat ion. t'c'.low up examinations were conducted at xB hours after :he challenge application. The subjects invo'i.ed in this study ranged in age from 16 to 68 years ol a^e. See accompanying i-'ble, summary and appendix. ^f eompany BanHteed. Oo 'wl eonte"' 'TseA BIOSEARCHiINCORrUATEO- P.O. BOX 6598 - PHl.AOELPHlAi PENNSYLVANIA191D1 - (215) 739-UW Project Number: 87-5670H Page 3 of 9 E.I. du Font de Neroours. & Conpany, Inc. - 16,759 Modified Draize Repeated Insult Patch Test Study In Human Subjects Conclusion: Signatures: FroB the results obtained in this study as described above with the particular group of subjects tested, the test article Is most likely not a primary akin Irritant. The test article Is most likely not a fatiguing agent. The teat article is most likely not a sensitizing agent. Submitted by Biosearch. Incorporated: lohn F. Wllson. M.D. ^Consultant Dermatologist f^JLrUjs., ^ Raymond^Hark, M.D. Medical Director Karl L. Gabriel, V.M."., Ph.D. President D oari^ B10SEARCH,INCORPORATE- DP.O. BOX8598 - PHILADELPHIA,PENNSYLVANIA19101 - (215) 739-iW Project Number: 87-5670H E.I. du Font de Nemours & Company, Inc. - 16,759, as supplied. Modified Draize Repeated Insult Patch Test Study in Human Subjects n 0 n j Table 1 i ^ 0 a Subjec t a *i Number m 0 1 24 48 2 24 48 3 24 48 4 24 48 Initial Exposure 5 24 48 6 24 48 7 24 48 8 24 48 9 24 48 1 0 0 0 0 0 0 0 0 0 0 0 0 C 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 T) 3 0 g 4 5 6 CD U (0 IX 7 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 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 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 8 00 00 00 00 00 00 00 00 00 9 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 } 10 11 0 HI 12 5 13 ? 14 a m 15 z z s 16 17 ^ 18 > 19 0 20 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 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 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 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 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 C 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 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 0 21 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 22 23 M 5 24 sj u 25 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 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 b & 10 10 24 - Reading 24 hours after applicat ion 48 Reading 48 hours after previous application but just before nextt a pplic;atio n Company Sanitized. Doe. not contain T8CA CBj Or 10 S 24 48 2 0 0 0 0 0 0 0 0 0 0 0 0 0 r\ t. 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 0 0 0 0 0 0 0 0 0 0 0 w.; ^ Project Numbelr: 87-56 70H E.I. dui Font de N(emourei & Coimparny. In C. - 16. 759, as G3Uppl ied. Modifie>d Drai ze fiepeaKed Ins ult Patch Te st St udy in Hiiiman Subjec:ts a 0 Ul T able 1 (c ont inuled) I n i In itia 1 Exp osure 2 8 Subjectt Nwber 1 24 48 2 24 48 3 24 48 4 24 48 5 24 48 6 24 48 7 24 48 8 24 48 9 24 48 1 26 27 28 Tl 29 P 30 g 31 S 32 g 33 34 35 1-, 36 37 g 38 !; 39 ^ 40 ,!! 41 ^ 42 S 43 $ 44 1 45 46 0 47 48 49 5 50 m 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 0 0 0 0 0 0 0 0 0 0 0 : , 0 0 0 0 u 0 0 0 0 0 0 >j u ; '? ' ^ 24 " Beading 24 hours after applicat ion " 48 Reading 48 hours after previous applica tion but just before next application ->^ ss^^. ^/^^ ^0^ 10 24 48 Orig Sit 24 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 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 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 ^/1 Project Numbe r: E.I. du Font de N Modified Draice R 0 ^ S i 2 " Subject ^? Niaber Pi 0 5) I 24 48 0 0 2 24 48 0 0 3 4 24 48 0 0 24 48 0 0 Table. I (continued) Initial Exposure 5 24 48 6 24 48 7 24 48 0 0 0 0 0 0 8 24 48 0 0 9 24 48 0 0 52 k 53 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 0 0 0 0 0 0 0 0 0 0 0 D 54 0 0 55 0 X 56 a u 57 5 58 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 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 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 59 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 60 B Z 61 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 0 0 0 0 0 0 0 0 0 0 0 S 62 0 PI 63 ^ 64 ? 65 -B D ^ 66 ! 67 | r 68 69 > 70 <B 0 71 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 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 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 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 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 0 0 0 0 0 0 0 0 0 0 0 0 0 C 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 72 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 73 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ^ 74 S 75 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 0 0 0 0 0 0 0 0 0 0 0 J u <a t 6 24 - 48 "^N-^^ ^, ^v ReadiIng 24 hours after applicat ion ReadiLnngg 48 hours after previous applies tion but just before next applicjition Or 10 S 24 48 24 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 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 0 0 0 0 0 ^-. ''*, ^y Projec t Number : 87-567yOH E.I. d u Pent c e Nemoursi & Coimpaniy. In c. - - 16, 759, as s uppli ed. Modifi ed Oraiz e Repeateid Ins ult Patch Teait St udy in Human Subject 8 a 5 T able 1 (ccintinue d) s n ? In it lal Expcisure n S Subjec C 5 Nuaber 3) 1 24 48 2 24 48 3 24 48 4 24 48 5 24 48 6 24 48 7 24 48 8 24 48 9 24 48 5 76 77 78 -o 79 1 80 S 81 5 82 10 " 83 84 n'. i B6 t 87 S 88 S 89 ? 90 5 91 S 92 r^ 93 S 94 ; 95 1 96 97 98 99 S loo 0 0 0 0 0 0 0 0 0 U 0 0 0 0 0 0 0 0 (1 it U U 0 ft u 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1) it U U 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 I 11 0 u 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 0 0 0 0 3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 I 11 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 n n 1) 11 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 0 0 0 0 n 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 n 1) it 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 n n (1 it 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 0 0 0 0 n 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 n n it 1) 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 0 0 0 0 n 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 n It 11 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 0 0 0 n n 1*1 " $* 1 Rftading 26 hours ftci pplicat ion - Reeding 48 hours after previous applies tion but just before next application <s^^ ^^^^ Ori 10 Si 24 48 24 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 n n 0 (i u u 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 0 0 0 0 0 0 0 0 0 0 0 0 0 Page 8 of 9 00 a < | 00 u k> >4 60-4 M CM a > SCO- 6 rf oc u ^ rt ^ ^coc. 000 000 000 000 ao I o o o d- 0 <M* 1 0 I 0 0 00 - ooo -aCM 000 CO * ooo 000 00 'aM JO w 03 . ID B > U-> B P- 3 i O 00 >< 000 -itCM 000 11 000 kl 3 00 CD -T G & X Id \0 st <M 000 00 -a- 000 -C*M 000 'a- 000 '* -it- <M 000 CO * ooo > CM 000 x 0 ^ a >a k> x-> 3 I 0 00 z 4) O z I M 000 5 a (U ooo j a ^i & .s 00 sr 000 fi CM 000 u U tJ U 41 's" J5J ^ CM n 0 0 0 -< --< ^ BIOSEARCH. INCORPORATED . P.O BOX 8598 & & m V L. 2 41 JQ e aa. o a W 3 u o < < ^ > ft 4) aa . ki a. I- kl &> a OB 01 b kl %% 4- CO N < 00 06 e e >J r4 ^ ^ a 4 00 N PHILADELPHIA. PENNSYLVANIA 19101 1'15) 739 Project Number: 87-5670H e. i. Ju 1'iinl ilr N-in;"iiB & l:iini|iiiy , Im . I1(.. /.' , nn n *lpp 1 i ! . Modified Draize repeated Insult Patch Test Study in Hunan Subjects 0 a 5 a n T Summary of Table 1 Z 3 1rt 0 Readings Initial Expoaure 1 2 3 4 24 48 24 48 24 48 24 48 103 103 103 103 103 103 103 103 5 24 48 103 103 6 24 48 103 103 7 24 48 103 103 8 24 48 103 103 9 24 4K 103 103 10 24 48 103 103 Challen Original Site 24 48 103 103 R 24 - Reading 24 hours after application 5 48 = Reading 48 hours after previous application but just before next application Project NiMbr; 87-S670H Appendix E.I. du Font de Nekoura & Coipany. Inc. - 16(719 Modified Draixe Repeated Insult Patch Tet Study in Human Subjects GRADING SCALE Huaan Patch Teat Studies Read 1 nf/s, 0 + l+ 2+ 3+ 4+ Interpretation negat ive suspicious slight erythema well defined erythema erythema with induration erythema with ulceratlori DEFINITIONS* Sens 11.1zation 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 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 tern such reactions have been called "skin fatique". 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 Cosmetic*. In DERMAL TOXICITY, p.46-53. Topeka, Kansas: Association of Food and Drug Officials of the United States. B10SEARCH.INCORPORATE- DP.O. BOX8598 - PHILADELPHIA,PENNSYLVANI1A9101 - (215; 739-U99 Ill BIOSEAFICH INCORPORATED III HI P.O. Box 8598. PUladdphte. PeoMylvnia 19101 /////A\\ ////// /// /// \\\/// Telephuae: (215) 7394499 Project Number: 87-5670H Testing Facility; Blosearch Incorporated 3408-50 "B" Street Philadelphia. PA 19134 Sponsor: F.I. du Pont de Neaours & Haske?1 Laboratories P.O. BOK 50, Elkton Road Newark, DE 19714 Comp&ny, Inc. Test Article: 16.760 Test Article Description: Blue fabric TeBt Article Received: Study Initiated: Date of Report: 05/14/87 05/27/87 07/06/87 Study Completed: 07/02/87 Teat: Modified Draize Repeated Insult Patch Teat Study in Human Subjects Object of Teat: Method of Test: To determine the irritating, fatiguing and sensitiz ing 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 103 volunteer Cauca sian subjects. These subjects were all determinr.d to be in generally good health, free of any visible skin disease or anomaly in the area to be patched. Each subject was required to read, understand and aign an Informed consent statement. The tost article was tested as supplied. CO^^ ^ ^ Project Numbar; 87-1670H E.I. du Font de Nemoura & Company, Inc. - 16,760 Modified Draixe Repeated Insult Patch Tet Study in Hu--n Subjects Method of Test: (continued) Results: Approximately a one Inch uquare portion of teat article was applied to ..he appropriate kin ite and covered with 2" Dermicel hypo-allergenic cloth tape (Johnaon & Johnson, New Brunawlck., N.J. 08903). The patch remained in place for 24 hours. At the end o: this period, the patch was removed and the site vac, examined for any dermal response. Scor ing of irrltdLion was in accordance with the scale in the Appendix. The subjects were then rested for a 26 hour period after which the skin site was again examined. A patch was then applied to the same cite as previous.v used. The second application was identical to the first and remained In place 24 hours. This procedu.e was repeated on alternate days until a series ot le-. applications had been made. The same site continued to be used throughout the study period as long as -.-> irritation or only minimal irritation (1+) was see-i after each 24 hour rest period. If greater irrigation (2+ or more) was noted then the subject was either rested or the contact site was changed at t-.r diacretion of the investigator. Approximatel. a 2 to 3 week rest period then elapsed after which a challenge application was applied in the same manner and to the same a lies described above. A duplicate challenge application was also applied in the same nanner to a virgin site* (previously untreated) .?n the other am. The challenge application was removed after 24 hours and the sites were exami-.cd for signs of Irritation or senaltlzatio-.. Follow up examinations were conducted at 48 hours oiter the challenge application. The subjects involved in this study ranged in age from 16 to 66 years of age. See accompanying table, summary and appendix. BlOSEARCHi INCORPORATE- DP.O. BOXB5<K - PHILADELPHIA,PENNSYLVANIA19101 - (215) 739-UW Project Nuaber: 87-1670H E.I. du Font de Nemours & Conpany, Inc. - 16,760 Modified Draize Repeated Insult Patch Test Study In Human Subjects Conclusion: Sianatiires; From the results obtained in this study as described above with the particular group of subjects tested, 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. Submitted by Blosearch, Incorporated: F. WiTson, M.D. Consultant Dermatologist / y^w^/^^.^^. Raymond ^ark, M.D. Medical Director Karl L. Gabriel, V.M.D.. Ph.D. President ^ ^<t B10SARCH, INCORPORATE- DP.O. BOX85W - , 8 ^ PHILADELPHIA,PEfWSYLVANIA1?101 - (215> PS^^W ^ ^ ^ .i yr Projec t Number : 87-567 OH F.. I . ft l Punt i > N nmiiill n f> I'n n|iai v i l 11.. /<>11 . .in n ..I.I.I Hodifi ed Draiz e Repeate d Ins ult Patch Tea t St udy i n Hujman c3ubjec-ts 0 0 ift C S Tablei 1 i ^ In itia I Gxpcasure 0 5 Subjec t ^ Huber 0 1 24 48 2 24 48 3 24 43 4 24 48 5 24 48 6 24 48 7 24 48 8 24 48 9 24 48 1 2 B 3 b B 4 0 5 if 6 a 7 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 0 0 0 0 0 0 0 0 0 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 0 0 0 0 0 U U 0 0 0 0 0 0 0 0 l) 0 0 0 U U 0 0 0 0 0 0 0 n U U 0 0 U U 0 0 0 0 0 0 n 0 U U 0 0 0 0 0 0 0 0 0 0 0 0 U U 0 0 0 0 8 0 0 0 0 0 (1 0 0 0 0 0 0 0 0 0 0 0 0 9 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 t I 10 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 s 11 0 m 12 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 0 0 0 0 0 0 0 0 0 0 0 5 13 ? 14 ^ ni 15 z z Ul 16 |< r 17 18 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 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 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 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 0 0 0 0 0 0 0 0 > 19 a 0 20 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 0 0 0 0 0 0 0 0 0 0 0 21 0 0 0 0 0 0 0 0 U 0 0 0 0 0 0 0 0 0 22 23 N if 24 -4 25 SS 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 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 & b 0 a 24 - Reading 24 hours after applicat ion 48 - Reeding 48 hours after previous applies tion but just before next appliccation "^wllwBB-^ "Wft y>^ "^^esss 10 24 48 Orig Sit 24 0 0 0 0 0 0 0 0 0 n 0 0 U U 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 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 0 0 0 0 0 0 0 0 0 0 0 V r Projectt Number: (B7-5670H E.I. d a Font de N(emours & Cmnpany, In c. - 16,7 60, as s upplied. Hodifi ed Draize Repeated Ins ult Patch Test Stu dy in Hu man Subje sts a 0 (11 Table 1 (con tin ued) n Sl Initial Exposure ? 0 Subject 5.0 Nimber a > -4 m 26 0 27 28 29 B b 30 g 31 X 32 0) U1 iO 33 a 34 35 -0 36 x 1s 37 33 0 ff) r B 39 I ? 40 B 41 m 7 Z 42 43 U1 < r < > 44 7 45 > 10 46 0 47 1 24 48 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 24 48 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 24 48 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 4 24 48 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5 24 48 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 48 49 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 M 50 5 0 0 0 0 0 0 0 0 0 0 j LJ ft ft 24 - Reading 24 hours after application 10 '0 48 - Rending 4A hourp aftfr previous appiicnt ion huf 6 24 48 7 24 48 8 24 48 9 24 48 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 n 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 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 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 G 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 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 0 0 0 0 0 0 0 0 0 ]iiBt bpForp npxf application O 10 24 48 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 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 ^ ^ ^^^firtfl '^tt^eCB, 00 a s ..4 ) M J hi rt 60"< <0 (M fl > 6-J 00 0) rBf 41 * ao w bri-C4O-4C1M 0 OOOOOOOOOOOOOOOOOOOCOOOOO 0000000000000000000000000 0000000000000000000000000 0000000000000000000000000 CO - 0000000000000000000000000 0 i* 0000000000000000000000000 CO * 0000000 <-'00000000000000000 ^- 0000000000000000000000000 00 -a- 0000000000000 00 0000000000 00 < 0000000000000000000000000 00 ^ 0000000000000000000000000 'CM 0000000000000000000000000 3 ffl 00 sf 10000000000000 00 0000000000 M !; 0 .0 & X \0 1 -a-0000000000000000000000000 JJ J3 CO - 0000000000000000000000000 <s 43 E- c m ^- CM eoooooooooooooooooooooooo 00 < 0000000000000000000000000 ^t- 4CM 0000000000000000000000000 00 ^ OOOOOOOOOOOOOOOOOOOOOOOOC a' ooooooooooooooooooooooooo 00 . OOOOOOOOOOOOOOOOOOOOOOOOO 4- CM OOOOOOOOOOOOOOOOOOOOOOOOO 00 OOOOOOOOOOOOOOOOOOOOOOOOO < ooooooooooooooooooooooooo w I3^ a w --rM<n^m<6^aochO-iCM<^<4'mraocr>0'^cMcn-9ir> BIOSEARCH INCORPORATED > P 0 BOX 059S PHILADELPHIA. PENNSYLVANIA 19101 ..-I'll 739 4499 '<- / ^ 7 Projec t Number b7-5611M E.I. d u Font dIe Ni.-mourai & Corrnpa ny, In C . - - 16, 760, as Eauppii ed. Modifi ed DraiiEC Repeate"d Ins ult Patch Te' l St udy i n Hijrnan Subje cts ID 5 in m Taible 1 (co>nt inlued) ^ a i Ini t ia 1 Expoisure3 ^ 0 D Subjec t a 0 Number a > 1 24 48 L 24 48 3 24 48 4 24 48 5 24 48 6 24 48 7 24 48 m-i 0 76 0 0 0 0 0 0 0 0 0 0 0 0 0 0 77 0 0 0 0 0 0 0 0 0 0 0 0 0 0 8 24 48 0 0 0 0 9 24 48 0 0 0 0 78 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 B 79 0 80 x 81 82 a Ul 10 l 83 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 0 0 0 n 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 n 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 84 0 0 u U u u U 0 0 U u u 1) 0 0 u 0 1) 85 t i 86 F > 87 88 0 m r -0 I 89 > 90 V m 91 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 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 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 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 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 0 z U) 92 -< 93 > z 94 > 95 (5 0 96 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 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 0 0 0 0 0 0 0 0 0 0 0 0 C 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 0 0 97 98 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 C 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5 99 ir 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 0 0 0 0 0 0 0 0 0 0 0 ^ u I? fc 10 24 - (A ^ 48 - i ^ Reading 24 hours after applicat ion Reading 48 hours after previous application but juat before next application '^^ ^^^e^ Ori 10 Si 24 48 24 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 u u 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 0 0 0 0 0 0 0 0 0 0 Project Number: 87-5670H E.I. du font de Nemours & Company, Inc. - 16,760, as supplied. Modified Draize Repeated Insult Patch Test Study in Human Subjects g Table 1 (continued) 5 z I8 Subject Number i'1io02i 103 Initial Exposure 123456789 24 48 24 48 24 48 24 48 24 48 24 48 24 48 24 48 24 48 Ori 10 Si 24 48 24 oOOoOOoOOoOOoOOoOOoOOoOOoOOoOOoOOoOOoOOoOOoOOoOOoOOoOOoOOoOOoOO W 0 24 " Reading 24 hours after application . 48 Reading 48 hours after previous application but just before next application ^ ^ ^ ^ ^ fl^ ' g ^ ^- ^ ^ Project Number: 87-5670H t.l. du roilL de Nfinuuly & Cuinpiiny , lili. . - l(j,/ljU, us .s.jppli.il. Modified Draizc Repeated Insult Patch lest Study in Human Subjects Readings Summary of Table 1 Initial Exposure 1 2 3 4 24 48 24 48 24 48 24 48 103 103 103 103 103 103 103 103 5 6 7 8 9 24 48 24 48 24 48 24 48 24 103 103 103 103 103 103 103 103 103 48 103 10 24 48 103 103 Challen Original Site 24 48 103 103 ,; 24 Reading 24 hours after application " 48 " Reading 48 hours after previous application but just before next application e0^ Project Number: 87-1670H Append! i. E.I. du Pout de Newours & Company, Inc. - 16,760 Modified Draize Repeated Insult Patch Test Study in Human Subjecf GRADING SCALE Human Patch Test Studies R-adir>R 0 + l+ 2+ 3+ 4+ Interpretation negative suspicious slight erythema well defined erythema erythema with induration erythema with ulceratlon DEFINITIONS* Sens!tization is a phenomenon which manifests itself by local efit-.^a on either skin or mucous membranes. It differs from primary irritation in -.-at it may also involve tissues remote from the site of application. These re&:Llons represent an allergy to a chemical which is not obtained on first conta:-., but requires a number of prior exposures for development. Repeated patch applications of substances Co both man and animalE -eveal that certain substances which, at a given concentration, do not ;-oduce primary irritation may elicit severe skin reactions after a nuin:-?r of exposures. Nevertheless, these reactions may not be considered incidc-ta of sensitization since after 10-14 days of rest the skin recovers its o-^ginal resistance to injury by the substance. For the lack of a better tem such reactions have been called "skin fatique". This latter term is a misn:.iier in that it does not laply a condition in which the skin has lost sign--: leant normal physiological function. This phenomenon consists of a subtle cha.-ige 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 TOXICITV, p. 46-53. Topeka, Kansas: Assocla-.ion of Food and Drug Officials of the United States. -, .Ooo.^0^ ^el.f--^ Sfl^ BIOSEAKH, INCORPORAT-EDP.O. BOX 65TO - PHILADELPHIAP. ENNSYLVANIHA101 - (215) T;8-**^ Ill BI08EAR.CH INCORPORATED /// /// P.O. Box 8598. Philadelphia. Pamuylvania 19101 /////A\\ Telephone: (215) 739-4499 ////// /// /// \\V// Project Number: 87-5670H Testing Facility: Biosearch Incorporated 3408-50 "B" Street Philadelphia, PA 19134 Sponsor: E.I. du Pont de Nemours & Company, Inc. Haskell Laboratories P.O. Box 50, Elkton Road Newark, DE 19714 Teat Article: 16,761 Test Article Description: tf":\. Article Received: Study Initiated: Date of Report: Blue fabric 05/14/87 05/27/87 07/06/87 Study Completed; 07/02/87 Teat: Modified Oraize Repealed Insult Patch Teat Study in Human Subjects Object of Teat: Method of Teat: To determine the Irritating, fatiguing and sensitiz ing 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 teat article to the upper arms of a group of 103 volunteer Cauca sian subjects. These subjects were all determined to be In generally good health, 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. ^ ,%^ Project Nuaber: 87-S670H Page 2 of 9 E.I. du Pont de Nemours & Coipany, Inc. - 16,761 Modified Oraize Repeated Insult Patch Test Study in Human Subjects Method of Test: (continued) Res'-ilta: Approximaiely a one inch square portion of test article was applied to the appropriate skin site and covered with 2" Dormicel hypo-allergenic cloth tape (Johnaon a Johnson, New Brunswick, N.J. 0^903). The patch remained in place for 24 hours. At the er.i of this perioil, the patch was teBOved and the site -as exaiined for any dermal response. Scor ing of irritation was in accordance with the scale in the Appendix. The subjects 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 previ;-isly used. The second application was identical :o the first and remained In place 24 hours. This procMure was repeated on alternate days until a series of ten applications had been made. The same site conl.-lued Co be used throughout the study period as long &5 no Irritation or only Minimal irritation (1+) was seen after each 24 hour rest per-od. If greater irritation (2+ or more) was noted then the subject ^-a-i either rested or the contact site was changed a; the di sc-rcL ion of the investigator. Approximat"!/ a 2 to 3 week rest period then elapsed afler whi:-, a challenge application wus applied In the same manner and to the same sites described above. A duplicate hallenge application was also applied in the same manner to a virgin site (previously untreated on the other arm. The challenge appi ir.atic- Wti.s removed after 24 hours and the sites were excnined for signs of Irritation or sensitizai.on. Follow up examinations were conducted at 48 hour; after the challenge application. The subjec-.s involved in this study ranged in age from 16 Lo 68 y:ars of hge. See accompanying Cable, summary and apperdix. B10SEARCH.INCORPORATE-D P.O. B0> -ISTO - PHILADELPHIA. FEH6YLVAN1A 19101 - (2l5> 739-UW Project Number: 87-5670H Page 3 of 9 E.I. du Font de Nemours & Company, Inc. - 16,761 Modified Draize Repeated Insult Patch Test Study in Human Subjects Conclusion: Signatures: From the results obtained in this study as described above with the particular group of subjects tested, 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. Submitted hy Biosearch, Incorporated: ^ ^ Fin F. WllIssoonn, H"T). ' insultant Dermatologist -Z-^*^ /^JL^t^ Raymond park, M.D. Med'cal Director ^ _ z ^ / _ Karl I., Gabriel, V.M.D. , Ph.D. President ^ ^ ^xW ^y' ^ ^ 810SEARCH. INCORPORATE- DP.O. BOX 8598 - PHILADELPHIA. PENNSYLVANIA191D1 - (215) 739-UW ^/ Project N11mbeir: 87-56 70H E.I. du Po nc <de Nemour s & Compa ny, In C . "- 16, 761, as suppi led. Modified Drai ze RIe peat e4 Ins ult Patch Teist St udy in H uman cSubject 8 01 0 Id ff > I Tables 1 n i z n 0 n T> 0 Subject a Number m 0 1 1 24 48 0 0 2 24 48 0 0 3 24 48 0 0 4 24 48 0 0 In it ia 1 Exp osure 5 24 48 6 24 48 7 24 48 0 0 0 0 0 0 8 24 48 0 0 9 24 48 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 o 3 0 4 a 0 5 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 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 0 0 0 0 a 6 i." ID (f 7 0 0 0 0 0 0 0 0 0 0 0 0 1) 0 0 0 (1 (1 0 0 (1 (i 0 0 (1 (1 0 0 0 U 0 0 U U 0 0 8 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 9 0 0 0 0 0 0 0 0 0 0 0 0 0 0 c 0 0 0 11 10 I 11 13 0 IT 12 r o Z ? 14 T) m 15 z 2 16 U) -< r 17 < > 18 Z ^ 19 5 20 0 21 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 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 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 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 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 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 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 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 0 0 0 U 0 0 6 0 0 0 0 0 0 0 0 0 22 23 G 5 24 25 sj 1*1 ID 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 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 0 0 0 0 0 0 0 c 0 0 0 0 0 0 0 0 0 0 0 0 0 0 & & 10 <D 24 - 48 - Reading 24 hours after applicat ion Reading 48 hours after previous application but just before next applic at ion Or 10 S 24 48 24 0 0 0 0 0 0 0 0 0 0 U 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ^-^- . ^ya ^CQ, ^ 1^*- Page 5 of 9 00 0 -^ M^ y u W60*p^4 C4O -N9 B > 01 ^ --4 90 -< a ao ^ 6>rM4l 241 < ^ 9 Ll CO CM 0 000000000000000000 00 00000 OOOOOOOOOOOOOOOOOOOOOCOOO ooooooooooooooooooooooooo 0000000000000000000000000 00 '!*' I 0000000000000000000000000 0 - tM I 0000000000000000000000000 00 - I 0000000000000000000000000 t 0000000000000000000000000 00 ^ I 0000000000000000000000000 < (M 0000000000000000000000000 00 ^T 0000000000000000000000000 ^"^ a o u a> U 3 r^ ^r CM ooooooooooooooooooooooooo aj c <b MOO 0000000070000000000000000 SCO) ~t < .0 4J <- C ^ U 3 00 < o. -n X ^- OOOOOOOOOOOOOOOOOOOOOOOOO a u oo -3- Iooooooooooooooooooooooooo a) -. t-i C in >> a -T OOOOOOOOOOOOOOOOOOOOOOOOO 3 4-1 M ,^ 4J 01 CO ~ OOOOOOOOOOOOOOOOOOOOOOOOO y E-i L> e J: h-J u -a- sf (M ooooooooooooooooooooooooo 4J >>* .&? C ^ OOOOOOOOOOOOOOOOOOOOOOOOO a 1 & Fk4 3 00 p1^ 'a- CM ooooooooooooooooooooooooo h-( x 0 o 1^ CD u L> 4J ul S 01 1 0 a a ^ v w b V N 6 u J3 *J ^ a \ e 0 Z a. 'V ^ 3 91 -^ \ " O w4 ) 111 IW 1- < ./ I - 0 ^^ B & S. Ml CO a' OOOOOOOOOOOOOOOOOOOOOOOOO CM ^ <M oooooooooooooooooooooooco 00 ^ OOOOOOOOOOOOOOOOOOOOOOOOO M^ .if tM OOOOOOOOOOOOOOOOOOOOOOOOO u U L. tl '^.0B >f^ocM.<coM^toM-^W<(Mntc^n.<f"tirr^>(>no<^io<onBnc0n-<^o^i'n^^^in'<<^o^r'-c<O^B^m0 o ^^ a Jl U ri & sa oa>. 4 I If a 3 --' i0* S.S & i 0. ^ ^ 11 0) J U u uj a a 0303 b Li e je ~T 00 M Sf 3060 ^ < a T ai ^ 's 35 IS, 0 <<r ^ S1-- ^ f5: p 0 SBto ^ ft CD 0 '" m Ja-^; gjp " j B10SEARCH. INCORPORATEO . PO BOX 8598 PHILADELPHIA. PENNSYLVANIA 19101 . 1215) 7f{- -if9 Sf T ./ ^ Projec t Number 87-56170H E.I. d u Font dIe N emourss & Cottpa ny. In C . - 16,7 61, as s uppi ied. Modifi ed Draizte Repeateid Ins ult Patch Test Stu dy in Huiman Subject s m 0 If ft > a n i z n 0 a Subjec t B 10 Number n 0 51 I 24 48 0 0 2 24 48 0 0 3 24 <8 0 0 4 24 ..; 0 0 T<able 1 (ccont inue d) In itial E.xp osure 5 24 48 6 24 48 7 24 48 0 0 0 0 0 0 52 0 0 0 0 0 0 0 0 0 0 0 0 0 0 53 0 0 0 0 0 0 0 0 0 0 0 0 0 0 o 54 0 55 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 0 n 0 x 56 57 a Ul 1C 0) 58 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 59 0 0 0 0 0 0 0 0 0 0 0 0 0 0 60 0 0 0 0 0 0 0 0 0 0 0 0 0 0 a I 61 0 0 0 0 0 0 0 0 0 0 0 0 0 0 E 62 0 63 FT r- T 64 '1 I ? 65 66 1) PT Z z in 67 68 < r < > Z 69 ^ 70 1C 0 71 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 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 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 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 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 0 0 0 0 0 0 0 0 0 0 0 0 u 0 0 8 24 48 0 0 0 0 0 0 U 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 0 0 0 0 0 0 0 0 0 0 9 24 48 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 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 72 73 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 0 0 0 0 0 0 0 0 0 0 0 F 74 ^ 75 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 C 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ^j bl 1C & t> ID <0 24 - Reading 24 hours after applicat ion 48 - Reading 48 hours after previous appi icat ion but just before next appiic at ion " ^ ^ a ^ ^ 9fl^ ^lye '"QL ff^ @!8y-- Ori 10 S 24 48 24 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 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 0 0 0 0 0 0 0 <0 a -s rt V 60 U b ri ^ ao.ri in CM o > 6 0) 00 q e --i 0) afi w < rt ^ l-i M CM 0 CO < 0 00 <t '! CM 0000000=00000000000000030 0000000=30000000000000000 0000000=00000000000000000 0000000=30000000000000030 OOOOOOC:00000000OOOOOOOOC 0000000=30000000000000030 0000000=00000000000000000 ooooooc==>ooooocoooooooc=c 00 - OOOOOOC=OOOOOOOOOOOOOOC=>0 00 ooooooe = seooooco ooooooc =10 00 ~ OOOOOOC;SOOOOOCOOOOOOOC3C oooooocsocooooeoooooooesc 11 k> 3 a 00 -3- OOOOOC-C: 3)COOOOOO=>OOOOOC=IC 0 a. x [d \o ~ CM OOOOOOC;3COOOOSOOOOOOOC3C c .c 00 3- ooooooc=oooooooooooooocoo -- CT ^ C in >> o ooooooc=ocoooocooooooocse 3 kO W OOOOOOCS30000000000000C30 ooooooc==>ooooocoooooooc=ie ocooooc = oooooocooooooocoe OOOOOOC = =)COOOOOOOOOOOOC=>0 U s < 0 i^ m >0 L, IT' 3 eg I 0 <u 0. 30 U & 00 - OOOOOOC==)00000000000=)0000 ooooooc=ooooooooooooooe=>e 00 ' OOOOOOC=OOOOOOOOOOOOOOC3C & z ' CM OOOOOOC = 3COOOOOOOOCTOOOCOO .^' 0 | -i 9 & u U U w -I s a B 10 z r*or^.-ro^oro^'aoo--co<atMo=--ao-a<o'ua"o>a>ooofocooo<o><eor-->c<rcMoi<Mc'ra>'m9>9o>poo0o>cch>0o BIOSEARCH INCORPORATED PO BOX B? PHlLALiELPHi* PE'-XS^LVANIt. 19101 215. T39 . Project Number: 87-5670H E.I. du Pont de Nemours & Company, Inc. - 16,761, as supplied. Modified Draize Repeated Insult Patch Test 3tudy in Human Subjects Table 1 (continued) Subject Number 24 48 2 24 48 3 24 48 4 24 48 Innitial Exxppoosure 5 24 48 6 24 48 7 24 48 101 102 103 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 0 0 0 0 0 0 0 0 0 0 0 8 24 48 0 0 0 0 0 0 9 24 48 0 0 0 0 0 0 Ori 10 S 24 48 24 0 0 0 0 0 0 0 0 0 24 - Reading 24 hours after application 48 " Reading 48 hours after previous application but just before next application pr-.jf. Niinihrr: 87 'if,7W E.I. du Font de Nemours & Company, Inc. - 16,761, as supplied. Modified Draize Repeated Insult Patch Test Study in Human Subjects 0 8 m > s S Summary of Table 1 z 8 g ? 5 Readings 0 Initial Exposure 1 2 3 4 24 48 24 48 24 48 24 48 103 103 103 103 103 103 103 103 524 48 103 103 624 48 103 10 7 824 48 24 3 103 103 103 948 24 103 103 48 103 10 24 48 103 103 Chall Original Site 24 48 103 103 24 - Reading 24 hours after application 48 Reading 48 hours after previous application but just before next application aL l09^^ ^lfo1^ ^CBl Project Number: 87-1670H Appendix E.I. Ju Font de Nemoura & Conpan), Inc. - 16,761 Modified Draize Repeated Insult Patch Teat Study In Human Subjects GRADING SCALE Human Patch Teat Studies Read 1nt 0 + 1+ 2+ 3+ 4+ Interpretation negative suspicious alight erythema well defined erythema erythema with Induration erythema with ulceration DEFINITIONS* Sensltlzation Is a phenomenon which manifests itself by local effects on either ukin or mucous membranes. It dtffers from primary trritation 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 akin reactions after a number of exposures. Nevertheless, these reactions nay 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 fatique". Thia latter tera la 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. BIOSEARCH.INCORPORAT- EDP.O. BOXBSTO- PHILADELPHIA.PENNSYLVAN1IA9101 - (215) TN-kVn