Document pBQLGx0o5yRajvqLqV2jQL80d

HAZLETON LABORATORIES AMERICA INC Chemical & BioMedical Sciences Division v. KINSM AN BLVD. P-0. BOX 7545 MADISON, W ISCONSIN 53707 PHONE (608) 241-4471 TLX 703956 H AZR AL M DS UD FINAL REPORT ROGER PERKINS MINNESOTA MINING & MANUFACTURING TOXICOLOGY SERUICES ST. PAUL, MN 55101 COMPANY SAMPLE: I-416 PURCHASE ORDER NUMBER: T837389-410 712 SAMPLE NUMBER: 70100355 SAMPLE ENTERED: 01/07/87 REPORT PRINTED: 01/27/87 ENCLOSED: P R I M A R Y E YE I R R I T A T I O N S T U D Y IN R A B B I T S RAL) D A T A A P P E N D I X METHOD, SUMMARY SIGNED: .\y\. S T E U E N M. G L A Z A STUDY DIRECTOR ACUTE TOXICOLOGY ..........Ir^'%71 DATE BY AND FOR H A Z L E T O N L A B O R A T O R I E S A M E R I C A , INC. RAW DATA FOR THIS STUDY ARE KEPT ON FILE AT HAZLETON LABORATORIES AMERICA, INC., MADISON, WISCONSIN. ^HAZLETON LABORATORIES AfsRICA, INC 3301 KINSM AN BLVD. P.0. BOX 7545 MADISON, W ISCONSIN 53707 Chemical & BioMedical Sciences Division PH O N E (608) 241-4471 TLX 703956 H A Z R A L M DS UD SAMPLE NUMBER: 70100355 SAMPLE: T-4016 PAGE EVE i r r i t a t i o n Objective: To d e t ermine the level of irritation p roduced sing l e e x p o s u r e of a test m a t e r i a l to one eye of a l b i n o a c c o r d i n g to the U.S. E n v i r o n m e n t a l P r o t e c t i o n A g e n c y s Testing Pesticides and Toxic Substances. following a rabb its Gu idei m e s for Test Material: T-4016 Physical Description: Purity and Stability: Thick brown liquid Sponsor assumes responsibility for purity and stability determinations. Test Animal: Young adult rabbits of the New Z ealand White strain were p r o c u r e d , m a i n t a i n e d i n d i v i d u a l l y in s c r e e n - b o t t o m c a g e s in t e m p e r a t u r e and h u m i d i t y - c o n t r o l l e d q u a r t e r s , p r o v i d e d a c c e s s to w a t e r a ^ 1 ib it u m and a measured amount of Purina High Fiber Rabbit Chow, and held for an a c c l i m a t i o n p e r i o d of at least 7 days. Six a c c l i m a t e d a n i m a l s , w e i g h i n g f r o m 2 3 5 4 to 2 5 1 4 g, w e r e c h o s e n at random for the test. The animals' eyes were examined within 24 hours p r i o r to test m a t e r i a l a d m i n i s t r a t i o n usi n g s o d i u m f l u o r e s c e i n dye p r o c e d u r e s . O n l y those a n i m a l s with no sign of o c u l a r injury or irritation were used on the test. Test animals were identified by animal number and c o r r e s p o n d i n g ear tag. R e a s o n for S p e c i e s S e l e c t i o n : T h e 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 animal of choice b a s e d upon its large orbit and n o n p i g m e n t e d iris. P r e p a r a t i o n of Test Material: was not determined. The sample was dosed as received. The pH Treatment: Each rabbit r e c e i v e d 0.1 ml of the liquid test m aterial p laced on the e v e r t e d l o w e r lid of o n e e y e , w i t h the c o n t r a 1a t e r a 1 e y e s e r v i n g as the untreated control. The upper and lower lids were gent l y held t o q ether for one s e c o n d to p r e v e n t loss of m a t e r i a l and then relea s e d . The eyes of the rabbits remained unflushed. Reason for Route of A d m i n i s t r a t i o n : based on the method of Draize. H i s t o r i c a l l y , the route of choice "^ ^ HAZLETON LABORATORIES AMERICA. INC Chemical & BioMedical Sciences Division 30! K I N S M A N BLVD. P.0. BOX 7545 M A D ISO N, W ISCONSIN 53707 PH O N E (608) 241-4471 T L X 703956 H A Z R A L M D S UD SAMPLE NUMBER: 70100355 SAMPLE: T-4016 EYE IRRITATION (CONTINUED) O b s e r v a t i o n s : The treated eyes were o b s e r v e d for ocular 1, 24 , 48 , 7 2 a n d 96 h o u r s a f t e r t r e a t m e n t . irritation at At the 7 2 - h o u r r e a d i n g , s o d i u m f l u o r e s c e i n was u s e d possible corneal injury. Irritation was graded and the Draize technique. to aid scored in re v e a l in g a c c o r d i n g to A n i m a l s w e r e w e i g h e d just p r i o r to test m a t e r i a l a d m i n i s t r a t i o n . P a t h o l o g y : At s t u d y t e r m i n a t i o n all a n i m a l s wer e e u t h a n a t i z e d and dlsea rded . HAZLETONfiO' LABORATORIES AMERICA. INC v<4;. 3301 KIN SM AN BLVD. P.0. BOX 7545 MADISON, W ISCONSIN 53707 Chemical & BioMedical Sciences Division PH O NE (608) 241-4471 TLX 703956 H A Z R A L M DS UD SAMPLE NUMBER: 70100355 SAMPLE: T-4016 PAGE EVE IRRITATION SUMMARY (CONTINUED) Test Animal: Albino rabbits - New Zealand White Source: Hazleton Research Products, Inc., Denver PA Date Animals Received: 12/16/86 Date Test Started: 01/08/87 Date Test Completed: 01/12/87 4 PRIMARY EYE IRRITATION SCORES* OBSERUATI ON PERIOD 6 Rabb it Mean 0.1 ml (Unwashed) 1 Hou r : 24 Hours 48 Hours 72 Hours 96 Hours 22.7 25.7 12.5 5.7 0 .0 * Th e P r i m a r y E y e Irr tat ion S c o r e is the t o t a l e y e i r r i t a t i o n s c o r e for all the a n i m a l s d i v i d e d b y the n u m b e r of a n i m a l s (6) at e a c h observation period. SAMPLE NUMBER: 70100355 SAMPLE: T-4016 EVE IRRITATION Animal Number F16208 F16219 F16220 F16221 F16222 F16223 O b s e r v t ion P e r lo d 1 Hour 24 Hou rs 48 Hours 72 Hours 96 Hours 1 Hour 24 Hours 48 Hours 72 Hours 96 Hou rs 1 Hour 24 Hours 48 Hours 72 Hours 96 Hours 1 Hou r 24 Hours 48 Hours 72 Hou rs 96 Hou rs 1 Hou r 24 Hours 48 Hours 72 Hours 96 H o u rs 1 Hour 24 Hours 48 Hours 72 Hours 96 Hours PAGE 5 (CONTINUED) Table 1 Individual Eye Irrita tlon Sco res Cornea AB 00 13 11 00 00 00 14 11 00 00 00 11 00 00 00 00 11 00 00 00 00 00 00 00 00 0 00 00 00 00 Score AXBX5 0 15 5 0 0 0 20 5 0 0 0 5 0 0 0 0 5 0 0 0 0 0 0 0 0 1) 0 0 0 0 Iris A 1 1 0 0 0 1 1 1 0 0 1 1 1 0 0 1 1 1 0 0 1 0 0 0 0 i 1 0 0 0 Score X5 5 0 0 0 5 5 5 0 0 5 5 0 0 5 c; 0 0 5 0 0 0 0 6 5 0 0 0 Conjunctivae ABc 343 232 2O0 2 10 000 3 4 n44 34 3 33 1 22 1 000 33n 3n l 21l n 0l 000 34o 34 1 2 11 2 10 000 34o 3 n4L 2 o4- 1 1 110 000 3 j> n o2 0 110 100 000 Score (A + B + C ) 2U 14 8 6 0 2108 14 10 0 112 8 6 0 18 16 8 6 0 18 14 8 40 16 8 4 2 0 HAZLETON LABORATORIES ANRICA. INC Chemical & BioMedical Sciences Division 33oT k INSMAN BLVD. P.0. BOX 7545 MADISON, W ISCONSIN 53707 P H O N E (608) 241-4471 TLX 703956 H A Z R A L M DS UD SAMPLE NUMBER: 70100355 SAMPLE: T-4016 EYE IRRITATION (CONTINUED) Table 2 Sodium Fluorescein Examination An ima 1 Numbe r F 1o 2 08 F16219 F16220 F16221 F16222 F16223 Observation Period P r e - i n i t a t ion 72 Hours NEG NEG NEG NEG NEG NEG INtb NEG NEG NEG NEG NEG NEG = No stain retention POS = Positive stain retention (area of cornea involved . Commen ts : No pain response (vocalization) was instillation of the test material. el i c i t e d from any animal following B l a n c h i n g of the c o n j u n e t lv a e w a s s e e n in all s i x a n i m a l s at 1 a n d 2 4 hours", in t h r e e a n i m a l s at 48 h o u r s a n c in t w o a n i m a l s at 72 h o u r . Corneal epithelial peeling was exhibited by four animal and by two a n i m a l s at 48 hours. at 24 h o u r s Pe fe r e n c e s : 1' GH iuticdhe l i nR'e.sK., , "Primary Eye S u b d i v i s i o n F, Irrigation Study," Hazard Evaluation: Pesticide Assessment Human and Domestic Animals, U.S. Environmental Protection H g e n c y O f f . c e of Pesticide and Toxic Substances Series 81-4, p p . 51-55 (November 1982). 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 T o x i city." A s s o c i a t i o n of Food and Drug Off i c i a l s of the U.S., pp. 46-59 (1975). 3 . 21 CFR 58. 4. D H H S P u b l i c a t i o n No. (NIH 8 5- 2 3 1985) G u i d e f o r t h e C are and Use of L a b o r a t o r y Anim al s. 10100355 pmrmrnt- - APPETITI I (1) Carne. (A) nnritT - degree of density (rea oost d u a take for rdinK) Ho opacity ELastilEySdTiaocremuibffl.trin.a.i.ucnt. Ha r*tsT, d a ta li of i r l *_____ lightly obaeura ~ datai! of irto risiti., ai, o f P * ! barely discernible Onmaum^ iris luvisibl 0 1* 2* 3* a* N n# (BX i n n nf inToiywt On* Quarter (or lese), but not toro _ __ Crostar tbo on* quarter, but loa tboB half Creator tban half, but lesa thaa tbreo quarters (reatar U n o bree quartera, uo t wbola- erea ~ " Ax B a 5 ttl (Z3 Tria (AJ Fold _ T-- <-- T oaollln, cirwM ooraeaX lajeado al! of tbea or -- >< of aoy thereof) iri etti! to light (sluggish reaotle 1 p o ^ t i e y . _ ~ to reaotioa to light, M r r t i c e , e-- daatruotio (asy - H of theae) " A* 10 (33 m jja s tta s (A> -meas (refer to palpebral ooojteotiva oaly) Teasels definitely injected----------- ------ Moro diffuse, deep- orlase rad. IndiTidual resasi sot easily discernible ' Diffus beefy red . '* (B) SttOBSA He suai U n i iy BralHnr aboee n o m i (includa nictitating laabra) Obvious srallinc "1" partial varalo of lids -- -- -- -- Swelling with lids about half alosad ," , , 3welling ultb lie baut half oloeed to ocaplataly oloaed 1 2 0 1 "2 * 3* 0 1 2* 3* * (C) QlAStlACIS He discharge -- Any _aa__eo__B_t_d_i_f_f_e_r_e_n_t__f_r_o (doe oot include oSserred 1 lanar eant.hu of n o m i aials) D l a n h e n witb soistenin o f the lid and boir* Juet adj to lid d a o b a r g e witb solstailing of tb lids snd hair, eaosidarabl area around tb eye -- -- -- -- -- -- -- -- 0 1 2 3 Score (A B C) x 2 Total Iteri)-- 3 Tbo t o t a l soot f o r tb# eye l a tba p o rn e , ir t a , an ecB juo etlva . iof 11 aoorea obtained for tbe S carrad f la u re in d ic e .poeieiw e a f f e c t . PRIMARY EYE IRRITATION TEST Initial Sodium Fluorescein Exam and Animal Body Weights HLA No. n o lO Q 3 5 S ~ Test Material: ______________________________ Physical Description: T V v >tX ''thrown. V ^ u l c i __ pH result: L C with pH meter No. A / 4 Dose: O. I nr1/ ______________________________ Review of folder preparation by: Til'll Date: (-Vfrl Room Number: l<P | ____________________________ _ Date Animals Received: 1 ( 0 _______________ Species: R A B B I T ___________________________ Strain: NEW ZEALAND W H I T E _______________ Source: HAZLETON RESEARCH PRODUCTS, INC. All animals appeared normal just prior to dosing. Technician: Date: t-g-71 A ninal Wo. n- ln& O O (m)OI (nC&fo Sex I n sicr*ia l c? llpn cf i Pc c? D $ Alfa ? Klon 0 "f f DVFl aoooallclcioeniwlog-ni n g Aniii Body Veighc* IgJ In ic ia c i n Day 7 Day IA k) silt k) k) M I X kJ J2 3 5 V - % \ Day 21 c ^ Dosed 1n the conjunctival sac. The upper and lower lids were gently held together for one second. M . Dosed directly on the cornea. The eyelids were re leased immediately without forced blinking or manipulation. * - Sodium Flupresceln Examination. N E G - Negative POS - Positive NA - Not Applicable U - Unable to determine pH Y - Yes N - No M - Male F - Female TECHNICIAN (V i DATE I35T7 \-g SCALE USED i r \~Z 15011 \ \ _________\ Time of Dosing: H f S / h r w Tech: M Date: l-fi2_ Time of First Observation: IQ'-IS ______ Tech: fort Date: |~13 1 _ Reviewed by: ^ l 1^______ Date: Primary Eye Irritation Test Observations est Material: - T - M O I L Test Eye: Right HLA No- n o i o o s s : Group: hJ/V_________ hitWashed: aJA- seconds following instillation of test material, * the test eye was washed with kIA- ml- of lukewarm tap water for Mft. seconds- ' L-^tJnwashed OBSERVATION PERIOD- I Animal No. Location of rnrppal Lesions T a i l ----- Head Cornea - Opacity Area ' Laos Vs J n o aff t.asn r\ /s \ J K J kJ. no 0 o 0O 1- -- 4S52_ r \t \ 0 e> _ o0 Iris Conjunctivae - ' " Redness Chemosis Discharge </ 3P Sodium Fluorescein Exam 3b H AW t * - rtr W* 3 /Ufi 3b 35 3 B Affi - _ 2 _____ 3p A/fi A/fi Technician "fang Date_________ NA - Not Applicable A - Petite hemorrhage B - Blanching C - Clear discharge . D - Purulent discharge E - Hair loss around the eye F - Necrotic Areas G - Unable to visualize due to severe swelling H - No reaction to light I - Injected J - Corneal epithelial damage, peeling 1C - Corneal epithelial damage, piling L - Corneal epithelial damage, pitting ft - 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 ^^eviewed By: " (4253A) Date: Eye I rr ita tio n Score: 2 Z H f'A'j Q est Material: Test Eye: Right Primary Eye Irritation Test Observations HLA no. H 0 1 0 0 3 5 - 5 " Group: -- fcJA_________ KiA Washed: jQA- seconds following instillation of test material, the test eye was washed with MA- ml- of lukewarm tap water for Mft. seconds. ' L^nwashed Animal No. Location of r0.poai lesio"* Pi" 'Gaos T a i l ----- Head Cornea - Opacity OBSERVATION PERIOD: rQ (4 h n u f ^ 1^ fca\< i LV(oO / V JN r \ 3^*85* \ o [Mrl a 2 2 2 ^ o Area Iris Conjunctivae ^ Redness ' 3 0- ft K \*' t t _ _ J _____ 3 n - - ____ Q _ _ O \* e> 3 Q. 3_ Chemosis 3M 0. 4 2 ___ 2.____ Discharge 3* 3 - ___Q.____ Sodium Fluorescein Exam M f t Mft Mft Mft- wA wW Technician // Date /- ? ~ ? 7 NA - Not Applicable A - Petite hemorrhage B - Blanching C - Clear discharge . D - Purulent discharge E - Hair loss around the eye F - Necrotic Areas q ~ ,,..able to visu-T'.ze due wC severe swelling . H - No reaction to light l - Injected J - Corneal epithelial damage, peeling K - Corneal epithelial damage, piling L - Corneal epithelial damage, pitting ft - Hypopyor* It - Corneal neovascularization P - Pannus R - Unable to visualize due to severe opacity S - Granulation scar tissue POS - Positive stain retention NEG - Negative stain retention ^ ^ v i e w e d By: ~ (4253A) -T--T---l--'-f-t-------- Date: -------\---------------------------- Eye Irritation Score: Primary Eye Irritation Test Observations est Material: - r - M o i u ______________________ __________ HLA NO. 101003551 Test Eye: Right____________ Group: -- klA;-- .------- jjft Washed: jjfir seconds following instillation of test material, * the test eye was washed with MA- rot of lukewarm tap water for Mft. seconds. ' i^flnwashed Animal No. Location of Corneal Lesions T a i l ----- Head Fl" U0 q 8 Cornea - Opacity ('oaao \t \ \ w oU no q -o (cpa3- O o Area \ \ o o ___ Q _ - p -- Iris o i x \x _ Q ____ J?-- CP Conjunctivae > Red^ness ' Chemosis > '2 - Q 3 3 \ 32 l \\ - 1 .... Discharge o V e" . \ \D J O - Sodium Fluorescein Exam Technician^ j _ A )Pt AJrt /oft___ A3 ft- A)/) KstV Date______ NA - Not Applicable A - Petite hemorrhage B - Blanching C - Clear discharge D - Purulent discharge E - Hair loss around the eye F - Necrotic Areas G - Unable to visualize due to severe swelling H - No reaction to light T - Injected J - Corneal epithelial damage, peeling K - Corneal epithelial damage, piling L - Coroeal epithelial damage, pitting M - Hypopyon f# - Corneal neovascularization P - Pannus R - Unable to visualize due to seveire opacity S - Granulation scar tissue POS - Positive-stain retention NEG - Negative stain retention Reviewed B y : _______ (4253A) , Date: V- 2.1-9T Eye I rr ita tio n Score: HV-ffl Primary Eye Irrita tio n Test Observations Q est Material,: - T-t-tOtb Test Eye: Right HLA NO. * 1 0 1 0 0 3 5 - 5 Group: fOAr__________ U/V washed: fjA- seconds following instillation of test material, the test eye was-washed with MA- Q-f lukewarm tap water for M(V seconds. ' U-'tJnwashed Animal No. Location of Corneal Lesions T a i l ----- Head r r O( . a o s a n V, / Cornea - Opacity Area Iris nO 0O 0n Conjunctivae " Redness ' e> 0- 2 Chemosis Discharqe \2 n Sodium Fluorescein Exam KVtx, N > ^ , nCo3 3 0 . i .aaj vy q q o _ ___ ____ 0 _ o _ _ ____ 0 : _ 2 ____ 0 _ Q ____ ' a. 0 \ _ J _____ _ L _ _ _ 1 _____ _ J _____ O _ Q ____ ____ j^Qy [V\PCk toPPy- Date /-//-7 NA - Not Applicable A - Petite hemorrhage B - Blanching C - Clear discharge D - Purulent discharge E - Hair loss around the eye F - Necrotic Areas R - Unable to visualize due to severe swelling H - No reaction to light I - Injected viewed By: " (4-253A) Date: J - Corneal epithelial damage, peeling K - Corneal epithelial damage, piling L - ComeaT epithelial damage, pitting M - Hypopyon K - Corneal neovascularization P - Pannus R - Unable to visualize due to severe opacity S - Granulation scar tissue POS - Positive stain retention NEG - Negative stain retention Eye I rrita tio n Score: Primary Eye Irritation Test Observations est Material: Test Eye: Right____________ HLA NO. fl 0 l 0 0 3 5 ~ 5 " Group: j J A _________ hlAWashed: MA- seconds following instillation of test material, the test eye was washed with MA- lukewarm Animal No. Location of Corneal Lesions o () qtap water for Mft. seconds. ' U 30S OBSERVATION PERIOD: ^(p hflarS r L^tJnwashed O1*223- ^ T a i l ----- Head Cornea - ODacity 0 n O . o ______ O _ Area 0 0 O : f ) ' q _ n Iris Conjunctivae - ^ Redness ' Chemosis Discharge 0 n- 0 0 0-- o n 0 rv . 0 0o r> 0o 0 --0 -- a o 0- O- 0 o n J 0__ __Sodium Fluorescein Exam tJ f\ A JA jJ ft. A jfr technician W ] Date_______ NA - Not Applicable A - Petite hemorrhage B - Blanching C - d e a r discharge , D - PuruTent discharge E - Hair loss around the eye F - Necrotic Areas G - Unable tn visualize dn* to severe swelling- H - No reaction to light I - Injected J - Corneal epithelial damage, peeling K - Corneal epithelial damage, piling L - Corneal epithelial damage, pitting - Hypopyon II - Corneal neovascularization P - Pannus R - Unable to visualize due to severe opacity S - Granulation scar tissue POS - Positive stain retention NEB - Negative stain retention Reviewed By: (4Z53A> .*r-rc ;k - TTl^ - Date: -v--r Eye I rr ita tio n Score: _ Q Q _