Document pBkg74mYNoErM95p0RQBR3KRj

FINAL REPORT m N N E S O T A ^ I N l N G & MANUFACTURING COMPANY TOXICOLOGY SERVICES ST. PAUL, MN 55101 SAMPLE: T-4101 PURCHASE ORDER NUMBER: T837389-410 753 SAMPLE NUMBER: 70905395 SAMPLE ENTERED: 09/23/07 REPORT PRINTED: 01/17/88 ENCLOSED: P R I M A R Y EYE I R R I T A T I O N / C O R R O S I O N ST U D Y IN R A B B I T S (OECD GUIDELINES) o Key Personnel o Method o Summery o References o Row Date Appendix SIGNED: S T E U E N M. G L A 2 A STUDY DIRECTOR ACUTE TOXICOLOGY ...........L - l S r DATE SAMPLE NUMBER: 70905395 SAMPLE: T-4101 PAGE 2 KEY PERSONNEL Acute Tnvicoloov S t e v e n M. G l a z e Study Director C a l v i n L. H o r t o n Group Leader Support Sarvicea S h a r e n L. Houiery Report Coordinator Quelitv Aaaurance Debra Curley Arndt Manager L a b o r a t o r y A n i m a l U e t e r i n ar LATI C i n d y J. C a r y , D U M Diplomate, ACLAM 3301 KINSMAN IVO. P-O. BOX 7545 SAMPLE NUMBER: 70905395 SAMPLE: T-4101 PAGE OECD EYE IRRUPTION O b j e c t i v e : Tt o d e t e r m i n e tthhae lleevveell oorf oo cc uuil a r i r r i t a t i o na l bp ir nood u creadb b iftol l o w i n g Guideline for Testing Chemical. Test Material: T-4101 P h y sica l D e scrip tio n : P u r it y and S t a b i li t y : S to ra g e and R e te n tio r Safety Precautions: Clear yellow liquid Sponsor assumes responsibility for purity and stability dtermint ions. The test material was s t o r e d at ro om temperaturi Any unused material will be discarded eccording to HLA Standard Operating Procedure. Normal handling procedure were used according to H L A S t a n d a r d O p e r a t i n g Proced ur e. S'. L a b o r a T o r y B n . a a l a " . If v a r i a t i a n . f r o . t h a p r . a c r i b . d ,,.j:H n n , isted they were d o c u m e n t e d and c o n s i d e r e d to have no on thl s t u d y outcome. No c o n t a m i n a n t s were e x p e c t e d to have been present ,n the f e e d e r w a t e r w h i c h w o u l d h a v e i n t e r f e r e d w i t h or a f f e c t e d t results of the study. Thra. aecl i.atad .....la, - g h i n 9 fro. 2 0 to r a n d o m fo r t h a ta at . T h a a n i m a l . ' a y a . " * r* ." ' T . in prior to test material administ ra ti on using s o d i u m fluorescein dye or o c e d u r e s . Only those enimals with no sign of ocular injury or irritation were used. Test animals were identified by animal number and co rr esponding ear tag. Reason for Species Selection: animal of choice based upon Th. i N e w Z e a l a n d W h i t e a l b i n o r a b b i t is the its large orbit and n o n p i g m e n t e d iris. Preparation and Administration of Test Material: received. The pH was determined to be 12.9. The sample was dosed as Treatment: Each rabbit r e ce iv ed 0.1 ml o f . Siting in to t h e e v e r t e d l o w e r lid of o n e e y e , w i t h tlhe c o n t r a l e t e r a 1 e y e s e r v , g as the untreated control. The upper and lower lids w e r e l ^ a i e d together for one second to prevent loss of material and then released. The eyes of the rabbits remained unflushed. SAMPLE NUMBER: 70905395 SAMPLE: T-4101 PAGE OECD EYE IRRITATION R e a s o n for R o u t e of A d m i n i t r a t ,o n : based on the method of Draize. (CONTINUED) Historically, the rout, of choice O b o a r v a t t o n . l Th . t r . a t . d . y . . - r . o b . a r y . d for o o u l . r i r r i . o . i o n ot 1, 24, 48, e n d 72 h o u r s a f t e r t r e a t m e n t . the Draize technique. i:.:z A n i m a l s were we i g h e d just prio r to test materiel e d m i n i . t r e t i o n . Pathology: At st u d y t e r m in at io n .11 anim al s war. a u t h . n . t i z . d and d is e a r d e d . St at is ti ca l tl.thod.1 Oth. r than a y r . , 0 ay. irritation ooor .a , no oth.r statistical method was performed. Lo ca ti on of Raw Data and Final Report: The raw data end a c o p y of th. final report will be r e t a i n e d in the a r c h i v e s of HLA. SAMPLE NUMBER: 70905395 SAMPLE: T-4101 OECD EYE IRRITATION (CONTINUED) SUMMARY Test Animal: Albino rabbits - New Zealand Source: Hazleton Research Products, Inc., Date Animals Received: 10/20/87 Uh ite Denver PA PAGE Date Test Started: 11/06787 Date Test Completed: 11/09/87 5 PRIMARY EYE IRRITATION SCORES* OBSERUATION PERIOD 3 Rabbit Mean 0.1 ml (Unwashed) 1 Hour: 24 Hours 48 Hours 72 Hours 6.3 6.7 0.7 0.0 * The for Primary all the E y e I r r i t a t i o n S c o r e is th e t o t a l e y e i r r i t a t i o n s c o r e a n im al s divi de d by the numb er of a n im al s (3) at each o b s e r v a t ion per i o d . HAZLETON i A fw eniC A . avc- Chemical & BioMedical Sciences Division 3301 K IN S M A N B LV D . P.O. B O X 7545 M A D ISO N , W ISC O N SIN 53707 P H O N E (60S) J41-4471 T L X 703S5S H A Z R A L M D S 0 0 SAMPLE NUMBER: 70905395 SAMPLE: T-4101 PAGE OECD EYE IRRITATION Animal Number F20334 F20326 F20329 Observation Period 1 Hour 24 Hours 48 Hours 72 Hours 1 Hour 24 Hours 40 Hours 72 Hours 1 Hour 24 Hours 48 Hours 72 Hours (CONTINUED) Table 1 Individua1 Eya Irritation Scores Co rnea AB 00 11 00 00 00 11 00 00 00 00 00 00 Score AXBX5 0 5 0 0 0 5 0 0 0 0 0 0 Iris A 0 0 0 0 0 0 0 0 1 0 0 0 Score AX5 0 0 0 0 0 0 0 0 5 0 0 0 C o n iunct iv a e ABC 110 110 100 000 110 110 000 000 210 100 000 000 Sco (A * B 4 4 2 0 4 4 0 0 6 2 0 0 Cornea A Degree of opacity B " Area of involvement Con junct ivae A - Redness B - C h e m o s is C - Discharge NEG P0S Tabla 2 Sodium Fluorescein Examination Animal Numbe r Obse rv t ion Per iod Pre-ini tat ion 72 Hours F20334 F20326 F20329 No stain rotent ion P o s it iwe s t a i n r e t e n t ion NEG NEG NEG (area of cornea NEG NEG NEG inwolwed).  HAZL5TOfV Chemical & BioMadlcal Sciences Division 3301 K IN S M A N BLVD. P.O. B O X 7545 M A D ISO N . W ISC O N SIN 53707 P H O N E (80S) 241-4471 T L X 703SS6 H A Z R A L M D S UD SAMPLE NUMBER: 70905395 SAMPLE: T-4101 PAGE 7 OECD EYE IRRITATION (CONTINUED) Comment s : No pain response was elicited from any animal following instillation of the test material. C o r n e a l e p i t h e l i a l p e e l i n g w a s o b s e r v e d in two a n i m a l s at 2 4 h o u r s . References : 1. O r g a n i s a t i o n fo r E c o n o m i c C o o p e r a t i o n a n d D e v e l o p m e n t ' s G u i d e l i n e s for Testing of Chemicals, Section 405, Acute Eye I r r i t a t i on /C or ros io n, a d o p t e d Ma y 12, 1981. 2. D r a i z e J . H . , " A p p r a i s a l of the S a f e t y of C h e m i c a l s in F o o d s , D r u g s , and Cosmetics - Dermal Toxicity", Association of Food and Drug Officials of the United States, pp. 46-59 (1975). 3. O E C D ' s P r i n c i p l e s of G o o d L a b o r a t o r y P r a c t i c e , A n n e x 2, C ( 8 1 ) 3 0 ( F i n a l ). 4. N I H P u b l i c a t i o n No. 8 6 - 2 3 ( R e v i s e d 1985). Personnel Signature Shoot Acuto Toxicology HU mo. T Q 9 Q 5 3 R S Mot Job Tltle Bocky Beckwith Stovo Beloungy Kon Bridges Pat Crary Sr. Lab. A n i m i Asst. Lab. Aninel Asst. Sr. U b . A n i m i Asst. Sr. Lab. A n i m i Asst. Shan* E1th Shown Frazier Lab A n i m i Asst. U b A n i m i Asst. Steven M. 61oza Nolly Hahn kovln Hamilton Jeff Hicks Calvin Horton Sharon L. Howory Gregory Johnson Group Leader Adnln. Clark U b . A n i m i Asst. Sr. Lab. A n i m i Asst. Group Leader ArniMstrative Asst. U b . A n i m i Tech. Paul Krebs Moyne tad1son U b . A n i m i Asst. Sectlon Sapervisor Scott NcConnell U b . A n i m i Tech. Shelley McConnell Dawn Conant U b . A n i m i Tech. Sr. U b . A n i m i Asst. Don Mavis Robin Olson Patricia Padghaa Joseph J. Daun U b . A n i m i Asst. U b . A n i m i Asst. T e m Leader U h . A n i m i Asst. Michael Patzka Lab. An i m i Asst. John Paulson Sr. Lab. A n i m i Asst. Jane Polnow Dennis B. Steiner Lab. A n i m i Tech. Lab. An i m i Tech. Michael Theslng U b . A n i m i Asst. Paula 6. Vangen Albert Olson Adnlnlstrative Asst. tanpower J1m Jlrschele LTE Ben Haley Sr. Lab Animai Asst. Eileen M. McConnell Admin. Clerk Annette R. Turner Manpower SlanitMEi M JU -U- W it f c r W1C/V-.U lnlliili g fi.. ___ M se, Z-- K*JL- PL1r - i=m . BOOT UEIHT/i^ jE RECORD Study tuie: Prlwary Eye Irritation Test Material! -f, m o i Physical description: pH result: wit tanna Ileter No. _ ose:o. I wl/, ( (Q ni equivalent!" . ^ d oiei wlth*^ 1-wL disposable syringe/Oft each dose Individually drawn up wit# a ii -ul Maint on Syringe bate an Inals received: / o - 2 <-7 - ^ 7 ________ Species/strain: Rabbit/New Zealand M h l i e __ ~____ ' Source: Hazleton Research Products, Inc. ________ ~ Room Ho: l/nl- i ______________________ ____ _____ Review of folder preparation by: fY ? bate: Surviving animals designated for sacrifice and discard. Technician / T ? Reviewed by:_________ ___________ pate: (00261/vmt) All anlwals appeared noma I just prior to dosing. . Technician: fcB bate: >l/u/A~l * - Sodtua fluorescein examination. NE6 - Negative. POS - Positive. NA - Not applicable. U - Unable to determinepH. V - Vocalization. E - Excessive pawingof treated eye. N - None Dosed directly on the cornea. The eyelids were released ioaedlately without forced blinking or Manipulation. Dosed in the conjunctival sac. / The upper and lower lids were gently held together lor one second. Time of dosing: J 1 Pfi______ Technician k &/f J Date: JZiR-f Time of first observation: 3 yS~/W Technician: /V7 Date: ///!%> (/ - / o * r ? Hu: primary eye irritation test observations Group: 1 Test material: "t - U i f l l ______________ _________________ Test eve: R1aht Washed: 0 3 seconds following Instillation of test.material. the test eye was washed with oft mL of lukewarm tap water for mft seconds. ^Unwashed Animal No. Location of corneal lesions Tall -- --- Head 0 n CS)() () Cornea - Oo adtv o oo ______in i_______ o oo His_____________ n o lx \ \ Conjunctivae > Redness ___) 1Q Chemosis _ J ___ Dlscharae o Sodium fluorescein exam 1 r> Oft ! n fOA Z 3" V Technician:, Date:______ J& 2 . EYE IRRITATIONr JSCwOuRnEt:; . Calculate*d B y : _ g f i i Verified Bv: ffJ icy -- D te_ f l ^ n Date ii-g-<T7 NA - Not appllcable. A - Petlte hemorrhaglng. B - Blanchlng. C - Clear dlscharga. 0 > Purulent dlscharge. E - Ha1r loss around the oye. F - Necrotlc areas. G - Unable to visualiza due to severo swelUng. H - No reactlon to Hght. 1 - Injected. 3 - Corneal epithelial daMge, peeling. K - Corneal epithelial damage, piling. L . Corneal epithelial damage, pitting. N - Hypopyon. . N - Corneal neovascularization. P - Pannus. R - Unable to visualize due to severe opacity. S - Granulation scar tissue. POS - Positive stain retention. NE6 - Negative stain retention. Reviewed by: (00261/vmt) nl Date : /3 ' % ' 8 7 HU: 1 0 q n S 3 <lS PRIMARY EYE IRRITATION TEST OBSERVATIONS Sroun: I Test Material: Test eve: Right UlQl _______________________________ lIA washed: o A seconds following Instillation of test.material, the test eye was washed with Mft mL of lukewarm tap water for ioa seconds. Jnwashed Animal No. Location of corneal lesions Tall ---- Head Cornea - Opacity Area ins Conjunctivae Redness Chemosis D QH /590 /t / / r\ o // // / \ <o () \\\\ Olscharae W' o Sodium fluorescein exam Technician:. - Q * . D*te:______// 7- 7 ____ Ain *# EYE I1KRKRI1 TIAATII1OUNH dSlCeOURKCE.:: - Calculated Bv: Verified Bv: fYJ t.1 Pate Date NA - Not applicable. A - Petlte hemorrhaglng. B - BlancMng. C - Citar dlscharge. 0 - Purulent dlscharge. E - Ha1r loss around the eye. f - Necrotlc artas. G - Unable to visualiza due to severe swelllng. H - No reactlon to Hght. 1 - Injected. J - Corneal epithelial damage, peeling. K - Corneal epithelial damage, piling. L - Corneal epithelial damage, pitting. N - Hypopyon. N - Corneal neovascularization. P - Pannus. R - Unable to visualize due to severe opacity. S - Granulation scar tissue. POS - Positive stain retention. NEG - Negative stain retention. Reviewed by:. (00261/vmt) J- Date: hla= T o q n . ^ q g PRIMARY EYE IRRITATION TEST OBSERVATIONS Group: 1 ________ T t -- ttrUl: J - U l Q i _____________________________ Test >v: Right lIA Washed: o A seconds following Instillation of test.material, the test eye was washed w1th O A nil of lukewarm tap water form a seconds. j^Unwashed Animal No. location of corneal lesions Tall ----- Head Cornea - Ifrffltx Area O O ins Conjunctlvae Redness O \ Chemosls Discharge 0 0 Sodium fluorescein exam A/A Technician: Oate:_____ ll-i-'il na - Not applicable. A - Petite hemorrhaging. B - Blanching. C - Clear discharge. 0 - Purulent discharge. E - Hair loss around the eye. F - Necrotic areas. G - Unable to visualize due to severe swelling. H - No reaction to light. 1 - Injected. \7 H C\> O 00 \ O GG 00 \ \ c> O 0 /N O \ v \ 0 MPr 0 A/fi EYE IRRITATION SCORE: Calculated By: verified By : iT' \ on Date I S Batel J - Corneal epithelial damage, peeling. K - Corneal epithelial damage, piling. L - Corneal epithelial damage, pitting. N - Hypopyon. N - Corneal neovascularization. P - Pannus. R - Unable to visualize due to severe opacity. S - Granulation scar tissue. POS - Positive stain retention. NE6 - Negative stain retention. Reviewed bv: (00261/vmt) f Y ^ ______ Date: 7 hla:_3 Q 9 q 2 S L PRIMARY EYE IRRITATION TEST OBSERVATIONS Grout): ________________________ Tost material: - UlGl ~ _____________________________ Test ee: Right lI^i Hashed: o A seconds following Instillation of test, material, the test eye was washed w1th k)A w L of lukewarm tap water f o r s e c o n d s . j^Unwashed Animal No. Location of corneal lesions Tall ---- Head 0 H V o () Cornea - Opacity Area Iris Conjunctlvae - Redness Chemosls Dlscharae O ft 0 rs ft 0 n00 00 c> 0 0 ft c> 0 0 \ \ \ \ \\ X- Sodium fluorescein exam .,, U t e w -- i k i - Technician:. Date:______ AJUn--n EYE IRRITATION SCORE: Calculated Bv: 34a_ Verified By : rf? Pate Date >-<5-37 NA - Not applicable. A - Petite hemorrhaging. B - Blanching. C - Clear discharge. 0 - Purulent discharge. E - Hair loss around the eye. F - Necrotic areas. G - Unable to visualize due to severe swelling. H - No reaction to light. 1 - Injected. J - Corneal epithelial damage, peeling. K - Corneal epithelial damage, piling. L - Corneal epithelial damage, pitting. M - Hypopyon. N - Corneal neovascularization. P - Pannus. R - Unable to visualize due to severe opacity. S - Granulation scar tissue. POS - Positive stain retention. NE6 - Negative stain retention. Reviewed by: ( 00261/vnrt) fP Date: i^ ' % 1 HU:Jc Q 3 SCALE FOR SCORING OCULAR LESIONS (ORAIZE TECHNIQUE) 11) cornea (A) Opacity - degree of density lires most dons* taken for reading) No opaci1ty ______________ w Scattered or diffusa area, details of Iris clearly visible Easily discernile translucent areas, details of Iris slIgRFIy obscured Opalescent areas, no^details of iris visible, size of pupil barely discernible Opaque, iris Invisible (d) Area of cornea Involved One quarter (or less), out not zero Greater than one-quirtar, but less than half greater tnan naif, but less than three-quarters Greater tnan tnree-quarters, up to uno la area ' U) Iris A X6x 5 Total maxlmus to 0 1* 2 3 a* 1 2 3 4 lA) Values norma I Folds aoove normal, congestion, suelllne, cirameorneaV injection (any or all oi these or coapinatlon of any thereof) Iris still reacting to light (sluggish reaction Is positive 1 No reaction to light, hauormaga. gross destruction (any or all of these) Ax S U ) Conjunctivas Total 10 ------ 2* VesseTr^?Si]lr*f*r' * p4,p* ,r*1 Im> bu,b*r eonjunctlvae excluding cornea and 1r1s) Vesselis definitely injected abooovwe noorrmamli Ma m d<#d..ee --------------a_____________. u ,, 0^" u f ; r I T * r er1" , " 1nd1,1du41 I e a sily discernible 0 1 2* 3 (d) Cnetas 1s No sue Iling Any fuelling aoove nomai (inclubes nictitating Uuvlous smelling with partial eversion of lids I1d...S--mmi.l.ionrgy uwlitmhi Smelling ultn lUlIiI_po-ss aa_0bo_OooVuu^Itt hNh.aa.llI.ffT. cCcll.IooOasSeeMdd~mt5~gn^.lv~.lj, 'ano) --- 0 1 2* 3* a* iC) Ulscnaree no discharge Any amount different from normal idoes not include sua fcaM nnfthnlulst Ao#f nnmomarl aaumlmalla"l a n l m a l ' s T TM * " " 5unt` W -------- 1 uiscnarge ultn moistening of the lids ano hairs just adjacent to lids-------------- -- ----, ulsenarge ultn bolstering of the lids and hairs, and considerable area around the eye 3 Score I A i | * c i i 2 Total m x la a i 20 jSSetlviST * ,0 r ,y * " th* *" o f 1,1 feor*f oHUIned fo r the cornea. I r is , and * Indicates positive effect. (FHSA Interpretation) 1 braize, J. Appraisal of the Safety of Chemicals in Foods. brags and Cosmetics brag Officials of tne Dermal United Toxicity, Association of States, pp. *6-59 (1975). Food and (00261/vmt)