Document 15K7roL6dkdMeQkebd34rY22a

AR226-2833 JWW^.' HO-TEST ^a^a^u^. ^nc. 810 FRONTAGE ROAD NOR HBROOK. ILLINOIS 60062 , REPORT TO E. I. du PCJNTde NEMOURS fc COMPANY SKIN SEJNSITIZATIOTNESTS WITH I FOUR SAMPLES IN ALBINO GUINEA PIGS ^'^^^^i^^Nilil'l^lll ^- -. :"?:.:.';-!'l:;^:3i^^,;:;-;w;^:@%;?!^i^a?';E9:l?3!r;g^ :^aN^^. 9wQu^aal tliQ--"Fl^T: IflNO FfiiQN.T^iS^'JBH^A^V ^w. NOKTHlBROftK; lUl^JJS <i>to62 Apr?3 12, 1973 Chief, Oral Toxicology S.e.ctwin E. I. duPont de ^eroours (i Corapainy Haskell Laboratory : ;.. : Wilmington, Delaware 19Mi We- ar:e. sub:mi^i ing; tedcesBiJth .onr^afcuaratory report dated April 12, 1973. prepared i ^ ctinnetetion wi^|i?tliifarbove study. VeiVy'^strvSy yours, JCC: sjn 3. ;i&.'i:;'iGa3andra 'Prestiden^t'; ^!$@ -::! . ^'..-'K . -a ^ '-s1. .,: :'.^ ^<ii .^il - l i'; ?!'!? Company SanKfeed. Does not contain TSCACBB AfcWW BIO-TEST ^aU^^.^w. REPORT TO E. I. du PONT de NEMOURS & COMPANY SKIN SENSITIZATION TESTS WITH FOUR SAMPi.'71? IN ALBINO GUINEA PI<3S I. Introduction \ At the request of E. I du Pont de Nerxiours & Company, a skin sensi- tization test was conductec with each of four samples. The samples were identified as; H-7857 H-7858 H-7859 IT-7860 Company Sanitized. Does not contain TSCA CBI Jivlt^hial B 10 T E S T /ffAwa^^. ^w, : ' 2 II. Summary j The results of the sk:,n sensitiaation tests in albino guinea pigs are summarized below. [ Results Not a Sensitizer A Sensitizer N.ot a Sensitizer A Sensitizer R e s pe ctfully submitted, INDUSTRIAL BIG-TEST LABORATORIES, INC. Report prepared by: [ ^.l<>fL^ rtg4?J>..Q 7 BTi eavvjpArfl eayrf'VKrierat^c-rh*\\mvwa^ rf Technician Aculte Toxicity Report approved by: Y- OJ^j^ w, (^bji Carmen Mastri, B. S. Senior Group Leader Acu:e Toxicity bc;psh .. I{eplingei< Ph. D. ^ Manager, Toxicology Company Sanded. Does not contain TSCA CB/ III. Investigational Proceoure The sarne procedure Vffaa followed with each test material. Ten albino guinea pigs ranging in body weight from 300-400 grams were used as test animals. E. V. Buehler*. Th<; test procedure was modeled after that of j Prior to the test, the irritation threshold was determined for the test material in the appropriate vehicle and the maximum non-irritating concentration was used for testing. The hair was clipped from the backs and flanks of the test animals, and closed patches were applied in the following manner: A Web;'il pad containing 0. 5 ml of the test solution was applied near the midline of the shaved back of each animal. The Webril pad was occluded vrith a. standard size Eleiatoplast coverlet (1-1/2 inch x 2 inches), and each animal was placed in a guinea pig re strainer for a six-hour exposure period. The animals were insulted in this manner nine times. Twenty-four and 48 hours after the initial insult and 24 hours after the rema ning eight insults the application sites were graded for ir ritation. * Buehler, E. V., "Dolayjed Contact Hypersensitivity in the Guinea Pig, " Arch. Dermat. 91, Feb uary 1965. Company Sanitized. Does not contain TSCA CB1 ^^'"Sf'^^SS^^. Jmtudt^al BIO-TEST 2^i^, ^ 4 Two weeks after the la9t exposure,;;aU ^t animals and four con trol animals from the sasne populat^n were ^lallenged with duplicate patches. The application attes were gcored ^r irritation 24 and 48 hours after challenge, t ny reaction in: tfee te^t group significantly greater than the maximum reaction produced: attc r the initial insult or that produced in the c antrol gro'np w^s co^eidered evidence of sensitization. : The scoring criteric: for erythema and eaema are presented in J Table I. ont^ 'any Sanitized ^Dno- es^co^,'"^CACBI ^vtuit^al BIO'TEST J!Mta^wi.\^ie. TABLE I Skin Sensitiz jation Test - Albino Guinea Pigs Scoring riteria for Skin Reactions Reaction Description Erythema Edema Injury in Dep'h Barely perceptible (Edg is of area not defined) Pale red in color and area definable Definite red in color and area well defined ^ Beet Cfr crimson red in color I Barel7 perceptible (Edges of area not defined) Area iefinable but not raised more than 1 mm Area well defined and raised approximately 1 mm Area raised more than 1 mm Esche rosis, Necrosis Maximum Primary Skin Irritation Score I Swt^Uid BIO-TEST ^a&ow^i. ^w, "' :'.'^. ^^'1 6 IV. Results The results of the skin sensitizatioh tests are presented in Tables ii - xiv. i'. /: ':":' :/; ':'/".' SompanySanitized D^o"e^^ ^."^nTSCACBf ""^--S------ "Li^i^^ ~ W ^^^^^--^ Wa'l.-te.il'Ei-.'.w.lAtW^'y^^Kf^^V^sS^"'^-' T'TSaayv-^TJS-S.; Tifj'-.^a-f ' ^ ^ ^SS^Sa^l^^BK'Srr-AP-iK^iaMfc*~~^5yS^sa51SK.&Wl.vr.'-w-'url y-wsl~*.sl.'w""~ Tr ABLE U A.^r l|; TEST MATERI H-7857 Skin Sensitizattioin Test - Alb>ino Guinea Pi gs Results Range-Find iing Group l Test Material Animal ---- ---GoRcentratioa------------------Number 0. 1% (w/v) Aqueous Solution 1 2 1. 0% (w/v) Aqueous Solution 3 4 |'"0 Kj. 10. 0% (w/v) Aqueous Solution 5 6 ^ M fi) i Key: a ^ EEdr.. == EEdryetmheama .8 i'3 2. 0 .1,1 ^w ID 3' ^ 1 Scores Folio wing Application Site 1 Si 24 Hours 48 Hours 24 Hours E^. Ed. Er. Ed. Er. Ed. 0 0 0 0 0 0 0 0 0 0 0 Q 0000 00 00 00 06 0000 00 00 10 00 ^fe^ 4 > . ".iswa.-iyts^.^aaaiiaaosaEaar.iiSKi!B^^yi, Cltr^yi--ss.-^y,j-.yj.i,j rt?'^ szEssSE^asas:~3'S^SS3'5SSfy-sasaE'FsavmSf.K- TABLE III "S" T EST 1MATERIAL ^J.0% (vt7 v) Aquec3US SO Lution of 7857 Skin Sensitizatio n Test - A Ibino Guline a I ^igs Res ults - Test Group ; l Scores r "ollowing Anima 1 ''lurnbcr InitialApplicati on 24 Hours 48 I- [ours Er. E d. Er. Ed Scores ]rollowinig Challenge Applications Insult Si te: Virgira Site: 24 Hours 48 Hou rs 24 H ours 48 H Er. Ed. Er. Ed. Er. Ed. Er. Q I ,^V'"' 8 '? j| 1';,.. ail"-.,, . ^ 1 0 0 0 0 2 0 0 0 0 3 0 0 1 0 4 0 0 0 0 5 0 0 0 0 6 0 0 0 0 7 0 0 0 0 8 0 0 0 0 9 0 0 0 0 10 0 0 0 0 0 0 0 0 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 0 0 0 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 0 0 0 0 0 0 0 0 & Key: ! 1 ^ 8 ? ^ ?: Sl P a ^ "-< f w ; 0 L > Er. = Erythema Ed. = Edema '; 0 'K S. iK- ?;, . IjM^afe^,^^ ^^^:^ ^s;-, V.&- ,.,. ^'i-asa^^fetdBE^1*!^^!.;.^^.!.^<-i^j,i^i.^.>S^&3a 5it^hial BIO. TEST /< N^^;"^":!tii|^l 11-1--"- 9 ' -', -''- :''.' ' '^'.'..i-/^1-1^.'!^'-^ . i-^ '; - - '': ', ' . ':^^: ".';'. . . ' \t .... ': t-. '' :',;'. TAB3L.&W- ^ B" 9 TEST MATERIA ..^^g .queous Solution N-^57 of Skini Sensitiz ition Test - Al^tno guinea Pigs Aninnal Number 1 2 3 4 Rejsults - Control Grouip 24 Er. Ch^enge ''...'. " -., ' ' :-"'''".-' S.c bape-s ^oJltoViong^ Site'1;;.'"."' ' ^ ' ^ ^ipplicatio n Site 2 Hours MHowra .24 Hours 48 Ed. '. 'Ek. :'EA.^ .;i.;..liEr. '";' ."."..i^' Ed.. Er. Hours Ed. 0 Q 0 Q 0 0 0 Or- :'. .:^.-.;;:^.- 0 0 ' 0 0 .' ,^" 0' 0 0 0 pi-..' ^ .. ; . ,;:<) ^ ,;o o 0 0 0 0 0 0 0 0 Key; I . Efr. =-- VEvry^ytjh.r emyy^a Ed. = Edema ' ' " ' ' '.-'. - .\ .' " ' : ' . ' r^ ^ :""1^ - %; ii : i^ '-"f '. ^ ' ^ .-.;'.;- !"'^ '"1 ^ . ';-- 1^ '1 . ;l1 ..:^t :| i^i '".' ' '? ^ ^Si' .'!! 1 :,i ,;':^ .-^ '^ '' 'S . '^i ;^ "-::?r . :^.' '-'.^n ' ^ . Do--not contain TSCA CBI 1 ^(| ^w^ TABLE V * TE:ST MATE:RIAL: CMMI Hh^H-7858 f^^^ Skin Sensitizat ion Test - All>ino Guinea Pi gs Test Material Concentration 0. 17o (w/v) Aqueous Solution i:''0 ;:;.. 0 &1 '.-.tU ;;i.,3 -. ">;*< ^ (0 B) 1. 0% (w/v) Aqueous Solution 10. 0% (w/v) Aqueous Solution' ' ' " '' i R" ' A CL ; ' ; 8 ; 1 - ' ?. Key: Er. = Erythema Ed. = Edema Animal Number 1 2 3 4 5 6 Ae suits Range-Fine iing Group Scores Follcswing Application Site 1 Si 2.4 Hours 48 Hours 24 Hours Eir Ed. JUr. JUd. ji.r. Jti.a. 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 0000 00 00 V) ! 0 ;; > i: ro ^. 'S-, K,\.. i&S^- sv- ^L;".;' TABLE VI TEST MATERIAL;[i10^. 0P%(^wq/vHj^-q7ue8o5u8s Solution of Skin Sensitization Test - Albino Guinea Pigs Animal .N-mnber - >coTes F<>llovnng Iilitial Appilica tion 24 Hours 48 Hours Rr , Ed. F.T Ed. 1 0 0 0 0 2 0 0 0 0 3 0 0 0 0 4 0 0 0 0 5 0 0 0 0 6 0 0 0 0 7 0 0 0 0 8 0 0 0 0 9 0 0 0 0 10 1 0 0 0 Results - Test Group Score s FoilLowing Chia-lleng(e Appliesitions Insult Site: 24 Hours 48 Hours Virgi n Site 24 Hours 48 --Ev^------35<i.----Ey. ------EA----Ev,----Ed. Er 0 0 1 0 0 0 0 1 0 1 0 0 0 0 1 0 1 0 0 0 1 1 0 2 0 1 0 1 0 0 1 0 0 0 0 1 0 2 0 0 0 0 1 0 1 0 1 0 1 0 Q 1 0 0 0 0 1 0 2 0 1 0 1 1 0 2 0 1 0 Z. Key; Er. = Erythema Ed. = Edema '^aitiol B 10. TEST i2 ,. TA@t-E VII ' .? TEST MATERIAL? .l.O.M^/vlAqne^is Solution of gMilliiniyH-^8 Skin Sen'sitiss??^ Test - A%HQ Guinea Pigs Rejuallts - Control Group, Animal Number 'SS^r ^i^"^':I":|'|.>.llx^ng '" ^K' a'i^llES^nge ApplSiciatetio2n . . 24 Hours 48;iHours ;24 Hours 48 Hours Er. E^. M'IP o^ o "ip ^< 0 ^ 0 ^: 0 ;^ 0 ^:.' p :a) Key: Er. = Erythema Ed. = Edema Company Sanitized. Does not conta.-n TSCA CBI || 11'^''' U|i; IB|}'' iiiiii?'1" ' Sn^iitiat '! '.'' r'^,^. ';'i - '. 1 '. 11 t, 6^ .a- . r - . , , , ^ ^CT^%Kagi'^r%?g^^p,r^- BIO-TEST Ja&Ma^iei, ^^^. ..:- ,^... . W '0 h U oo op bo 00 00 ^ ^ U \ N i-* i-* --< M a 00 00 00 w^ W '0 g" H iii U 13 0 a W & ^ ''* n' ^M 00 00 -- ^ , ^ '-;"..:, : I-|H"., . fc j;;. ^' g. 11 .@i - f(1i- B,|; ^ & Ifet ?' It ^^ ^ l^a',.; p: |S. Na;,1 | ;tete'i:- In..?:, $:; rS''i I.'!-' 1 ,1?: 4 i-'^i! 1.,; J." b': ''! V':' .9 F 1 B . s os m 0< | ? ft rt i w a 1 ^ a ^ | ^ 5 T3 .5 h 3 L-1 ' M f 1 " 0 s g' (Q ^ H S < < a rt ^55- ^ 13 M s E-i H .a ^.^ ^ .-y ^ s 2 " fi pi H ,x ifl v> M e ^ -a -< u) b0 0 <pl .wg{ h (R " '05 ^ i-i . <h 9^^, 3 0 a ^ M 0-^0 L| 0 4-1 rl in m 'O " 0 a <f K' N y 00 00 00 00 ^< h rt (U C J .5 5 g < z ^ N fr4t C o a a rt H (-1 (9 4J $ C <4 (U ** " w r! U 0 H U ' 3 ^ ^ (0 n g ? '2' < ? ^ i? --l d 00 00 -< -< 0 -' 00 00 0 0 ' 0 i-< M ir in >o g tf ^ ^ ^ 'S3 U) (0 n (A 0) 0 ? 3 5* ! < < ? ^ i i rt 6 w ri JS C i-1 C > U n 'O y u ^ g 0 0 11 n ^ . . ^' o U M '0 !^ U U Company Sarnitized. Does not contain TSCA CBI )" ' .1 - .1i '1 | ^1 I'"t'S "' ;i .4' "'>, ^ .1 :^ s . ; (; -;' '..:-""- .",- "'t .- ' :! :' ^ :..i'i .^ ''& K; J -j El - ' '. v^^ .. : \\:':';iiH - v ( ;."1; - "'i-^'"""'. --T-p--r; TABLE IX TES T Iv-IATERIALL; JL 1% MMM ^ (w/v) B--N [ueous H-785 S 9 o l u t i on of Skiri S.'nsitissat ion Test - AlIbi no G-uinea Pi gs i RLCS ults - Test CSro up Anima 1 Niimbe r 1 24 Houirs Er. Ed. 48 H ours Er. Ed. Scor es Following InisuIt No. 2 3 4 5 24 Hours Er Ed. Z4I Hours E r. Ed. ~~m 2^1 H[ours E r. Ed. Sour s E. Eci. 6 24H ours Er. Ed !"- Ii;,1 ."',;,. 2 3 ^ ? 4' 1..1 5 6 ^ 7 8 n 9 p. 10 : 0 : 0 : <0 w i 3 [ a Key: 1'.: 0 - 0 ,: ^t ; ET 3 S-1 (fl Er. = Ed. = - = Note; 0 ' CB r 0 0 1 0 I 0 1 0 0 0 0 0 0 0 0 0 I 0 1 0 0 0 1 0 0 0 0 0 1 0 1 0 0 0 0 0 0 0 1 0 2 0 2 0 2 0 1 0 2 0 1 0 - 2 0 2 0 2 0 1 0 2 0 1 0 2 0 2 0 1 0 1 0 1 0 2 0 1 0 0 1 0 1 1 0 1 - - - 1 0 1 1 0 1 1 0 1 0 0 1 1 0 1 0 0 1 Erythema Edema Animal died. Test matcirial concentration Mxras reduced to 0. 01% prior to insult No. 4 to increas ed irritation. The animals were insulted seven times rather fatigue. 0 1 0 0 2 0 0 1 0 - - - 0 1 0 0 1 0 0 1 0 0 2 0 0 1 0 0 1 0 and the insult site than nine in order ^J'^SfJ. Swtudi^ial BIO.TEST ./wW^i '''''^j^lSjIISI ^.".(W'R;^^ ' :'.''>.. ^wfl^ 15 Animal Number 1 2 3 4 5 6 7 8 9 10 "-;s; 1 '^.i L:(hT0Wl%(^w^to ^Wo5u9e TE3T MIATEKIA M : . -. . '.. '' '!'': . :::^ ..--. fs^ Solution c>f > ^:y Skin1 Sensitiz atlon Test - Ajll3i ae jl^uinLea Pigs --^'- B iefintta, - Te.flit ^F t^ ;; >?;.; S< [Qr^p-aEi'c^IiOw^ngniai^; j^eng?e Applicatbion .law ^^.'^;T:.';'"'''^ Virgiin Site '''"'^'II^s:^: 324 24 Hour a Er. Ed. .": Hours ET.,.' ^'^'iEdilu '..". ^1Er. Ed. ";- ,' .; ' :^- Xi^^' 48 Hours Er. Ed. il'i 1 -0; : i 0 ^ -^^'. 1 6 .'^ 1 0 ^Ul "t 1: ^ 0 0 ^. ? . ' 0 0 0 0 0 0 1 0 : . . '. . :. --:w - - ' i^ 1 0 2, ::^:^ 0 'm^ 2 9 ," 2 0 2 '. -;:^ i 0 2 Oi^^':' "'"..? i 0 -- 1 0 1 0 1 0 1 0 ".^i 1 0 2' . '.^"' 0 1. ^'/'ll 1 0 :'./^!^: .^2 2 0 '. 2.- 0 " - -1 ";: .;'' ''.i^ -.. .'. . ,^ :....','' : i.' .'"'.^''s 1 0 1 0 2 0 Key: Er. = Erythema Ed. = Edema - = Animal Jied. ':%: "^:' ^.. ' ':-^3: Comparty Sanitized. Does not contain TSCA CB! ^^^^^^^^^^^^^^SB^ . D^hU BIG-TEST Mft^e^ " . T^E-Xt j;-1-' ^3 ~ TEST MATERIAL [3oi.oi;(igii>i(<wti/vS|,^^-^''7i|9 Skin 5ensjltiizi9 tion:.'I. 'e-'st .- : Ai.l.^.u- no^$^iiinea Pigs ^y ^l^-^C<)ntrpl'a!|yiO^ :" ;; *' ;' -.' - , -<-1 "(^-'' . Animal Number ,J..^4 '^i il'ie.s ^RiallfMviine^i^llti^ssngeApplication L.'-Sia ^.'^.il"'^^-':^' M Site 2 24 Hou^ '''-(t^Ieu^^. Hours 48 Hours Er. Ed. E.''.'!'^;,.^::::^^a|r. Ed. Er. Ed. ^^-^i oo 1 1 Q :. '^:- ,\^. -r^jin o i o 2 2 :^'" ' ..^ '^^'yN.'ii o i o 3 1 '0 1. :";^,^:^.^l 0 1 0 4 1 0 i o ''^^ :?-.^ : ..;' Key: Er. = Erythema Ed. = Edema ^'l "| i ,| ^i ^| '''; ^.j'j: .:':^ .'^ ^ '^ - I'''t .'.1 ",,! '"^ 'S3 .;a|3 i^ -% ,;'3'FH ^ ;'.a ^ "'Pai; .','^!?^ ;,^5a| ^ ^s ,-;J-..';-'S-'^l,<4-"'a1 ^aA fip'i.M ^^San,^--^------------3,nrs04CB;^iSft as ^^r-' .^k. ^---''BB 'Sty flB TABLE XII - ' TEST MATERIAL:R(||rt^<nH-7860 ' Skin Sensitization Test - Albino Guinea Pigs - 1: Test Material Concentration ; 0. 1% (w/v) Aqueous Solution ; 1: 1.0% (w/v) Aqueous Solution ? & 10.0% (w/v) Aqueous g.:/g. ,^ ; S- -------------------------------------- . M | a) 3; r ' n. g7 (i> i (" ,K,. ey: Er. = Ed. = Erythema Edema Solution 0 ' 0 }-.0 sr 3' ^ ^ ? Animal Nunahjex 1 2 3 4 5 .6 P.esults - Range-Finding Group Scores Following Application Site 1 S 24 Hours 48 Hours 24 Hours - .-r. ---Ed.- - E1. Ed.- Er.-- ^Ed. 000000000000 00 00 0 0 0 0 0000 . .; "'0' :.^t).-;,',^ o 0 000000 . '0' :.<) ' ' ^y |; ^ 0 5 l;:7:'.-- 0 l^^. BUS;';'. ! 0 < i (/1 ' I1' ^ N' i (6 ; 0. .'. 0 0 ! W :. W 1 1 ' 0 {: 0 t. 3 r f ^. S. r =' ^ -w i 2 0 CO TABLE 3mi TES1r M A T E R I A L : G10. ^^^ 0% ^^^^ ^ ( ^ w ^^ /v m ^ y qu H- e ous 7F860 Stolution o> iSkin Sen sitizatio n Test - Albino Guineai Pigs Anima 1 Kumhr 1 2 3 4 5 6 7 8 9 10 Sco;es JFollowiaig InitiailA]pplicatic>n 24 HoiITS 48 H ours Er. F<L. Er. Ed. 0 0 0 0 0 0 .0 0 0 0 0 0 0 0 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 0 Resialts - Te st Grou;P Score s Follownng Cltiallenge Appliesitions Insult >Site: Virgin Site: 24] lours 48 He>urs 24 Klours 48 H ----Er.----Ed.-- --Kr-.---- -Ed^ ----Eo.-- 0 0 0 0 0 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 1 0 1 0 0 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 1 1 0 1 0 0 0 0 1 0 1 0 0 6 1 0 0 0 0 0 0 0 Keys Er. = Erythema Ed. = Edema m.;A5iliSw...-;.---;,.ii^c-";^- I TABLE XIV - TEST MATERIAL;_JO, Q%jWvyk><|fteousSolution of l ' . ^' .''""- Skin Sensitization Test - Allnno Guinea Pigs Ie suits - C;Qntrol<3jp6up Animal Number 1 2 3 4 Scores ^Foltpynng C^lllenge Application Site I Site 2 24 Hours 48 Huurs / 24 H ours 48 Hours Er. Ed. :.. Er ..'/^..fia.- Er. Ed. Er. Ed. 1 0 0 \ r':.'.' 0 0 0 0 '0.'.- ', 0 0 0 0 0 0 ^r''...y: 0 0 0 0 . :. Q '.'."^'' '; 0 0 0 0 0 0 0 0 0 0 Key: Er. = Erythema Ed. = Edema . , .;.;;,,- ':\; ~ ''.. :.'' '. - '^; Company Sanitized. Does not contain TSCA CBI