Document BRLNoV95rZ79M9ygKBGrmZ1aJ

AHAZG _ 06/ PFOA Acute Toxicity - J 000847 HAZLETON LABORATOIRES AMERCA.MC. 3301 KINSMAN BLVD.. P.O. BOX 7545 MADISON. Wl 53707 USA FINAL REPORT Karen Armstrong 3M Toxicology Services Building 220-2E-02 St. Paul, MN 55144-1000 Sample: T-4416 HLA Number: 91201741 Enclosed: Primary Eye Irritation/Corrosion Study in Rabbits (OECD Guidelines) o Key Personnel o Methodology o Summary of Results o References o Raw Data Appendix Signed: Study Director Acute Toxicology PHONE (608) 241-4471 FACSIMILE (608) 241-7227 TELEX TLX 703956 HAZRAL MDS UD -- e?, -to Date " ~ ~ TM o ( T T r 5 r s 0 HAZLETON LABORATORES AMEF6CA.MC. 3301 KINSMAN BLVD.. P.0. BOX 754S MADISON. Wl S3707 USA HLA Number: 91201741 Sample: T-4416 Acute Toxicology Steven M. Glaza Study Director Section Supervisor Steven R. Sorenson Study Coordinator Patricia Padgham Group Leader Sharen L. Howery Report Coordinator Page 2 KEY PERSONNEL Quality A?SMHtn<? Deborah L. Keller Manager Laboratory Animal Veterinarian Cindy J. Cary, DVM Diplomate, ACLAM PHONE (608) 241-4471 FACSIMILE (608) 241-7227 TELEX TLX 703956 HAZRAL MDS UD * CORNINO LUxntory Samte Company 000849 HAZLETON l a b o r a t o r ie s a m e r c a . i \ ic . 3301 KINSMAN BLVD., P.O. BOX 7545 MADISON, Wl 53707 USA HLA Number: 91201741 Sample: T-4416 Page 3 METHODOLOGY Objective: To assess the relative level of ocular irritation/corrosion produced following a single exposure of a test substance to one eye of albino rabbits according to the Organisation for Economic Cooperation and Development's Guidelines for Testing Chemicals.1 Test Material: T-4416 Physical Description: Purity and Stability: Storage and Retention: Safety Precautions: Clear colorless liquid Sponsor assumes responsibility for purity and stability determinations (including under test conditions). The test material was stored at room temperature. Any unused material will be returned to Sponsor according to HLA Standard Operating Procedure. Normal handling procedures were used according to HLA Standard Operating Procedure. Test Animal: Adult albino rabbits, Hra:(NZW)SPF, were procured, maintained individually in screen-bottom cages in temperature- and humidity-controlled quarters, provided access to water ad libitum and a measured amount of High Fiber Rabbit Chow 5326, Purina Mills, Inc., and held for an acclimation period of at least 7 days. Animal husbandry and housing at HLA comply with standards outlined in the "Guide for the Care and Use of Laboratory Animals".2 If variations from the prescribed environmental conditions existed, they were documented and considered to have no effect on the study outcome. No contaminants were expected to have been present in the feed or water which would have interfered with or affected the results of the study. One male and two female acclimated animals, weighing from 2148 to 2500 g, were chosen at random for the test. The animals' eyes were examined within 24 hours prior to test material administration using sodium fluorescein dye procedures. Only those animals with no sign of ocular injury or irritation were used. Test animals were identified by animal number and corresponding ear tag. Reason for Species Selection: Historically, the New Zealand White albino rabbit is the animal of choice based upon its large orbit and nonpigmented iris. Preparation and Administration of Test Material: The sample was dosed as received. The pH was determined to be 9.9. PHONE (608) 241-4471 FACSIMILE (608) 241-7227 TELEX TLX 703956 HAZRAL MDS UD 000850 0 HAZLETON LABORATORES AVtERCA. rs)C. 3301 KINSMAN BLVD., P.O. BOX 7545 MADISON, Wl 53707 USA HLA Number: 91201741 Sample: T-4416 Page 4 Treatment: Each rabbit received 0.1 mL of the test material placed into the everted lower lid of one eye, with the contralateral eye serving as the untreated control. The upper and lower lids were gently held together for 1 second to prevent loss of material and then released. The eyes of the rabbits remained unflushed. Reason for Route of Administration: Historically, the ocular route is the route of choice based on the method of Draize. Observations: The treated eyes were observed for ocular irritation at 1, 24, 48, 72 and 96 hours, and Days 7, 14 and 21 after treatment. At the 24- and 72-hour, and 7-, 14- and 21-day readings, sodium fluorescein was used to aid in revealing possible corneal injury. Irritation was graded and scored according to the Draize technique. Animals were weighed just prior to test material administration and at weekly intervals throughout the study. Termination: At termination of the experimental phase, all animals were euthanatized and discarded. Statistical Methods: No statistical method was performed. Location of Raw Data and Final Report: The raw data and a copy of the final report will be retained in the archives of HLA. PHONE (60S) 241-4471 FACSIMILE (608) 241-7227 TELEX TLX 703956 HAZRAL MDS UD OOn^m tO LAtKWMovy Sorvic-- Company 000851 HAZLETON l a b o r a t o r e s a m e s c a . rsic. 3301 KINSMAN BLVD., P.O. BOX 7545 MADISON. Wl 53707 USA HLA Number: 91201741 Sample: T-4416 Page 5 SUMMARY OF RESULTS Test Animal: Albino Rabbits - Hra:(NZW)SPF Source: Hazleton Research Products, Inc., Denver PA Date Animals Received: 12/19/89 Start Date (In-life): 01/10/90 End Date (In-Life): 01/31/90 Average Primary Eye Irritation Scores* Observation Period Average Score 1 Hour 24 Hour 48 Hour 72 Hour 96 Hour Day 7 Day 14 Day 21 41.0 49.0 36.0 38.3 34.3 16.0 6.0 0.0 * The average primary eye irritation score is the total eye irritation score for all the animals divided by the number of animals (3) at each observation period. PHONE (608) 241-4471 FACSIMILE (608) 241-7227 TELEX TLX 703956 HAZRAL MDS UD O O RNM O U fto m o y Sarvien Company 000852 HAZLETON UABORATORCS AM ERCA.NC 3301 KINSMAN BLVD.. P.O. BOX 7545 MADISON. Wl 53707 USA HLA Number: 91201741 Sample: T-4416 Page 6 Animal Number F31165 F31127 Observation Period 1 Hour 24 Hour 48 Hour 72 Hour 96 Hour Day 7 Day 14 Day 21 1 Hour 24 Hour 48 Hour 72 Hour 96 Hour Day 7 Day 14 Day 21 Table 1 Individual Eye Irritation Scores Cornea AB 14 14 13 14 13 21 00 00 Score AXBX5 20 20 15 20 15 10 0 0 Iris A 1 1 1 1 1 0 0 0 Score AX5 5 5 5 5 5 0 0 0 14 14 14 14 14 11 11 00 20 20 20 20 20 5 5 0 1 1 1 1 1 1 1 0 5 5 5 5 5 5 5 0 Coniunctivae AB 23 33 32 32 32 21 10 00 3 3 2 2 1 0 0 0 23 33 32 32 32 21 21 00 3 3 1 2 2 0 0 0 Score fA+B+C12 16 18 14 14 12 6 2 0 16 18 12 14 14 6 6 0 F31194 1 Hour 24 Hour 48 Hour 72 Hour 96 Hour Day 7 Day 14 Day 21 14 24 14 14 13 12 00 00 20 40 20 20 15 10 0 0 1 1 1 1 1 0 0 0 5 23 3 16 5 33 2 16 5 32 1 12 5 32 1 12 5 32 1 12 0 21 0 6 0 00 0 0 0 00 0 0 Cornea A - Degree of opacity B - Area of involvement Conjunctivae A - Redness B - Chemosis C - Discharge PHONE (608) 241-4471 FACSIMILE (608) 241-7227 TELEX TLX 703956 HAZRAL MDS UD OOMmiwO LUwmoy Stm cm Cempm* 000853 H A Z L E T Q [\ LABORATORIES AMERCA.IMC. 3301 KINSMAN BLVD., P.O. BOX 7545 MADISON, Wl 53707 USA HLA Number: 91201741 Sample: T-4416 Page 7 Table 2 Sodium Fluorescein Examination Animal _______________________ Observation Period Number Pre-initiation 24 Hour 72 Hour Dav 7 Dav 14 D a y _ H F31165 F31127 F31194 NEG NEG NEG POS (80%) POS (55%) POS (15%) NEG POS (100%) POS (80%) POS (5%) POS (5%) POS (75%) POS (80%) NEG NEG NEG NEG NEG NEG - No stain retention POS - Positive stain retention (area of cornea involved) Comments: A pain response (excessive pawing of the treated eye) was elicited in all three animals following instillation of the test material. Blanching of the conjunctivae was observed in all three animals at 1, 24, 48, 72 and 96 hours, and Day 7. Petite hemorrhaging of the conjunctivae was observed in two animals at 24 hours. Corneal epithelial peeling was seen in all three animals at 24, 48, 72 and 96 hours, in two animals at Day 7, and in one animal at Day 14. REFERENCES 1. "Acute Eye Irritation/Corrosion," Organisation for Economic Cooperation and Development's Guidelines for Testing of Chemicals, Section 405 (adopted May 12, 1981). 2. NIH Publication No. 86-23 (revised 1985). 3. Draize, J. H., "Eye Mucosa," In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics - Dermal Toxicity, Association of Food and Drug Officials of the U.S., pp. 49-50 (1975). PHONE (608) 241-4471 FACSIMILE (608) 241-7227 TELEX TLX 703956 HAZRAL MDS UD a o o m n m q I hornno Swviom pw yany 000854 I LA-. . g i a c i m i PERSONNEL SIGNATURE SHEET ACUTE TOXICOLOGY Name Job Title Signature Initials Becky Beckwith Ann Bursaw Anthony Cass Cindy J. Cary, DVH Kari Gassen Lab Animal Technician Sr. Clerk h J3& _ Lab Animal Assistant Lab Animal Veterinarian Sr. Lab Animal Assistant n k \\lyTYU-l CcXiljL |0 yCoAtv K o h , A M rkA A a rx _ <xa % Steven H. Glaza Section Supervisor _______ Ben Haley Sr. Lab Animal Assistant Jeff Hicks Sharen L. liowery Lab Animal Technician Research Assistant sP:Lfj'jUVj Jim Jirschele Wayne Madison Bud McDonald Eileen McConnell Henry Mikula Albert Oleson Lab Animal Assistant L~ PutJilz/ ^ Senior Section Supervisor C(h 'p >*f 0 . Sr. Lab Animal Assistant $ i< A /V c fty \a J c / Administrative Clerk Lab Animal Assistant fin ite.00 ^ o ':C r Sr. Lab Animal Assistant JjL f^.vt-i / j >7<cS\ .^ AO Patricia Padgham 7V> Jane Pol now cypL Steven R-. Sorenson Dawn Thieding / Annette R. Turner 4io (09/11/89) -- 000855 EC3 UZlur.T/UUSE HE LORD hla: q i a n n m S:'j;!y title: Primary Eve Irritation Test materia :: T-TUIto Aiiys i c al d e s c r i p t i o n : r t t f t n c v taitbu.tia cH result: q.S with CORUI.'IG pH MEIER 110.05510 t ; s e : Q , \ m uA o ( n i e o u i v a l e n t ) _cosec w i:n a i-wL d i s p o s a b l e s y r i n g e / ^ t \ each cose " i n s I v idduuaa l l y d r a wn up w i t h a - in.L hn a i . - ..ini ct o n Sa y r i n g e D a t e a n i m a l s r e c e i v e d : ________ i ? / i q | y i ________ Spec i s s / s t ra i r. : Rabbi s/ wew ea tane n u e S our ce: Hat 1eton Research Rrcouc: : , Inc. Room t l o : M In t Review o f fo ld e r preparation by: Jff.! Hate: In itia l An ir.:J 1 tlo. Green Sex cr # F3 H U S nan i r ? H ec-. ,9 ii . 9 Pain Response Following D o : ino c F Animal body W eights (g) In i t i Jt icn Uav 7 Dav 14 Uav 21 SCO 2238 <& 2 J c L _ 2&19 Z .E S & I'J'lb 1 d 2.L o ? ^ F 2 lM 73 3* 1 z s t< 4 11 A ll anim als appeared normal j u s t prior t o des i n o . Technician: bate: ' / ip fO o * - Sodium f lu o r e s c e in exammat ior.. HEG - n e g a t i v e . AOS - P o s i t i v e . IIA - H o t app I i c a p l e . U - U n a b l e t o d e t e r m i n e pM. V - Voca I ia a t ten. Z - E x c e s s ive pawing of treated eye. II - H o ne Mft Dozed d i r e c t l y cn t h e c o r n e a . The e y e lid s were released irr-.e d 1 a t e 1v w i t h o u t f o r c e d b lin kin g cr m anipulaticn. Techn ic ian < Date 1990 /J leale Used KTP.OII u /& ltd e `L HOOZ1 1 10 * 1 `/ n 1 L^ 1' <s `/ m ------ '/a/_ Dosed in the c o n ju n c tiv a l sac. The u p p e r and low er 1 ids were g e n t l y h e l d t o g e t h e r l o r une secund. Time o f d o s in g : lo .5 o c > ro T e c . m l c 1 a n _ ____J> .. _ u a t e : `Im M D <to02L! 1 _ U a t e : _ J A l3 f2 . a u r v i v i n g animals d e s i g n a t e d f o r s a c r i f i c e and d i s c a r d . T e c h n i c i a n ____Date / - ty . c ^ 000856 Reviewed by: { C0c51/ viat) ------------------------------ ^ Date: 2 ^ - f S - ^ C a Approximately 5 minutes prior to test nateTfai^diainistration _______ drops of proparacr?n?''fh-5cif _____ _________ Lot ___________ ) v/s^^nrs^jj 1ea into __ eyels) of each rabbit. Technician Date LA: qiaonMl PRIMARY EYE IRRITATION TEST OBSERVATIONS Group:______j________________ Test material:_~ T- IU_______________________________________ Test eve: Right Washed: seconds following instillation of test material, the test eye was washed wi th mL of lukewarm tap water forn& seconds. u*-tlnwashed Animal No. Location of corneal lesions Tall ---- Head Observation Period: __ 1 m C\) ( )3 n u s nan \ O Cornea - Opacity ii ) Iris Area v i1 i1 Conjunctivae Redness 3 2 i Chemos1s 3 33 D1 scharqe Sodium fluorescein exam Technician:____ 77S Date:___________ 'Jihi iC ^ ___ 3C 0 ^ EYE IRRITATION SCORE: airs________________ Calculated By: Date i - i u - ^ r i Verified Bv: ... J t Date' NA Not applicable. A - Petite hemorrhaging. 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, K - Corneal epithelial damage, L - Corneal epithelial damage, M - 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: Date: iS r S O 000857 HLA:. q i a o n M l PRIMARY EYE IRRITATION TEST OBSERVATIONS Group:_____ j________________ Test material: T- M4 ii*____________________________________ _ Test eve: Right m Pi Mashed: j r seconds following Instillation of test material, the test eye was washed wi th oA mL of lukewarm tap water (or>m seconds. i^^Unwashed Animal No. Location of corneal lesions Tall ---- Head Cornea - Opacity 3 $ 1 f 1 Iris Area *4 \* Conjunctivae Redness Chemos1s 3.A& A D1 scharqe *>C PtKO&l*Sodium fluorescein exam \nt*4 CS)0 z. 3I* A 2J- 0 Technician: Date : l~t i-lO EYE IRRITATION SC0RE:^ U c . a q . O _________ Calculated By: Date Verified By:_____ 4 # Date NA -- Not applicable. A - Petite hemorrhaging. 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. 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. NEG - Negative stain retention. d>A)TJiy Hr <2)CAULU<_ATKm J GRAGA. tc=t /-/-So Reviewed by:_ Date: OOOS^P LA: q i a o n M l PRIMARY EYE IRRITATION TEST OBSERVATIONS Group:______[______________________ Test material: T- il._______________________ _______________ Test eve: Right__ Washed: (j r seconds following Instillation of test material, the test eye was washed wl th pts mL of lukewarm tap water lora seconds. ^ -Unwashed Technician:_______ ^~7-/ Date:___________ S-/J-Y NA -- Not applicable. A - Petite hemorrhaging. 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 - Injec ted. EYE IRRITATION SCORE: r-,______________ Calculated By:_____ g-* Date /-/u-Qa Verified By: /jA Pate hvQn 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. NEG - Negative stain retention. Reviewed by: Date: 000859 HLA: q i a o n M l PRIMARY EYE IRRITATION TEST OBSERVATIONS Group:______!______________________ Test material: T~ M ^ i u ............................... ..... ... Test eve: Right >iPt Washed: o r seconds following Instillation of test material, the test eye was washed wi th m , ml of lukewarm ^ Unwashed tap water torm seconds. Animal No. Location of corneal lesions 3 Ta11 ---- Head I1U5 J-- ceZ \ j - /v n oo Cornea - Opacity ! !/ Area i1/ Iris /r Conjunctivae Redness Chemos1s J- D1scharqe 3 c. Sodium fluorescein exam Pc>s / r / y' . r7^ J /c Zbsw Z \\ \ \ Technician:. Date:______ EYE IRRITATION SCORE: ^ Calculated By:_____ Date /d. i b 3 d _ Verified By:______ /-f Date NA - Not applicable. A - Petite hemorrhaging. B - Blanching. C - Clear discharge. D - Purulent discharge. E - Hair loss around the eye. F - Necrotic areas. G - Unable to visualize due to severe swe1 1 1 ng. H - No reaction to light. I - 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. NEG - Negative stain retention. Reviewed by: Date: 2 .- - O n 000860 HLA: qiaonMI PRIMARY EYE IRRITATION TEST OBSERVATIONS Group :______j________________ Test material : T- il.________________________________________ Test eve: Right Washed: >j r seconds following Instillation of test material, the test eye was washed with nts ml of lukewarm tap water fornc\ seconds. t ^ fclnwashed Technician: Date:_______ ! - ! < - / - < ^ 0 NA - Not applicable. A - Petite hemorrhaging. 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. EYE IRRITATION SCORE: ^ ______________ Calculated By:_____ Date /-/y Verified By: sfR Date `/zil4n J - Corneal epithelial damage, peeling. K - Corneal epithelial damage, piling. L - Corneal epithelial damage, pitting. H - 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. <D>orrR:^ ficcrtts Reviewed by:_____ S > Date: 000861 HLA:_ q i a o r n u PRIMARY EYE IRRITATION TEST OBSERVATIONS Group:______j________________ Test material: T - M<4 il.________________________________________ Test eve: Right ifH Washed: jft seconds following Instillation of test material, the test eye was washed with m <\ ml of lukewarm tap water for><& seconds. __tJnwashed _________________________________01nervatlo 1 Period: ~1 fwi Animal No. Location of corneal lesions 3 \ oo Tall ---- Head \ Cornea - Opacity ) Iris Area 11 2, 1 X- O Conjunctivae Redness ln Chemosis D1 scharqe o Sodium fluorescein exam ( o A Ie 1 O ?*<> i 1 o N*-> Technician:__________ Date:_____________ EYE IRRITATION SCORE: Calculated By: Verified By:______A __________ Date Date `/iJqo NA -- Not applicable. A - Petite hemorrhaging. 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. 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. NEG - Negative stain retention. Reviewed by: Date; 000862 .HLA:_ q i a o n M l PRIMARY EYE IRRITATION TEST OBSERVATIONS Group:______|______________________ Test material: T- M M i u ________________________________________ Test eve: Right Washed: seconds following Instillation of test material, the test eye was washed wl th Mts mL of lukewarm tap water torn(x seconds. Animal No. Location of corneal lesions 3 C) ( ') OTall ---- Head nus \(X)O __Unwashed C) Cornea - Opacity Area n [o 0 iD Iris Conjunctivae Redness Chemosis oO 1 2- O o IO 0 1 scharqe Sodium fluorescein exam 0 r> sy* P-i, O Otc> Technician : Date :_____ A-- ./ A w NA -- Not applicable. A - Petite hemorrhaging. 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. EYE IRRITATION SCORE: (. r>_________ Calculated By: / < Date 7?M^rT Verified By: ^ Date i - M - q p 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. NEG - Negative stain retention. Reviewed by:_ Date : 000863 HLA:. q i a o n M i PRIMARY EYE IRRITATION TEST OBSERVATIONS Group:_____ [______________________ Test material : T- M4 i l . ________________________________________________________ Test eye: Right Mashed: ijtx seconds following Instillation of test material, the test eye was washed wl th jfr ml of lukewarm tap water forncx seconds. ^-Unwashed Animal No. Location of corneal lesions Tall .... Head \Observation Period: 11U S ,, 9 \ kftb C) 0 Cs)O C) Cornea - Opacity Area Iris oo oo oo o o o Conjunctivae Redness Chemosis oo no o Q 0 1 scharqe 0o O Sodium fluorescein exam Technician: _________ Date:________/ - .^1- Q O EYE IRRITATION SCORE:. -Q :-Q . Calculated By:__ Datei-.-\i -<=>o Verified By:____ Date ~ > - r - 9 0 NA -- Not applicable. A - Petite hemorrhaging. 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, 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. NEG - Negative stain retention. Reviewed by: .I s Bate: 7. - ^ - ^ 000864