Document grMdEDXOE9Bdvn5wazOEV32G

Bye Irritation Test with H-21095 in Babbits Laboratory Project ID Haskell Laboratory Report No. 271-95 Author Carol Finlay ) Study Completed On April 20, 1995 Performing Laboratory E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box 50 Newark, Delaware 19714 J : J j Jj Medical Research No. i i Company Sanitized. Does nm oes not contain TSCA GBl ' l iiaadyBiiiiaihimi^iaiidiBtiiWBai.friwaft Page 1 o f 10 msj itti Physical For; Composition: I Contaminant: Purity: ! CAS Registry Ho.: Sponsor: None 30% None available DuPont Specialty Chemicals E. I. du Pont de Nemoursand Company Wilmington, Delaware Study Initiated - Completed: 4/3/95 - 4/20/95 In Life Phase Initiated - Completed: 4/4/95 - 4/7/95 I if * ` : Ev Irritation Test with H-21093 la Urtftlf H-21095 vis evaluated for acute eye irritation potential in 2 rabbits. An aliquot of 0.01 aL of the test substance was Instilled i n t e ^ h e loser conjunctival sac of the right eye of each rabbit. Ajprwelnately 20 *cond after instillation, the treated and control *y** of 1 rabbit uere w M h ^ . The treated and control eyes of the remaining rabbit were not ******* eyes of the rabbits were examined on the day of treatment and on days 1, Z, and 3 following treatment. H-21095 produced mild conjunctival redness in the treated unwashed eye. Mild conjunctival redness, slight cheaosls, and moderate blood-tinged discharge were observed in the eye washed after trmataent. of both rabbits were normal by 4 hours after instillation. No clinical signs of toxicity were observed during the study. Under the conditions of this studyi H-21095 was a mild, transient eye irritant. Work by: Reviewed by: Reviewed and Approved for Issue: ( t - A r t r j A tftfc;---- Toxicology Associate . TracyA. Fiiiiben Toxicology Technician *4- tI Q / ^ S ** ff|uy~ Study Director CF/alw Company Sanitized. Ooes rip?conia: :JI INTRODUCTION The purpose of this study vis to evaluate the acute ey irritation potential of H-21095 in young adult rabbits. MATERIALS AND METHODS A. Aniaal Husbandry Young adult female HM:(NZV)fBR rabbits were received from Hare Marland, Hewitt, New Jersey. The rabbits were housed singly in suspended, stainless steel, wire-mesh cages. Each rabbit was assigned a unique identification number which vas recorded on a card affixed to the cage. The last 3 digits of the identificatior number were vritten on the inside of each rabbit's ear with a water insoluble marker. The rabbits were offered approximately 125 grams of Purina Certified High Piber Rabbit Chow* #5325 daily during the study. Vater was available ad libitum. Haskell Laboratory has an animal health moritoring program. This program is monitored and administered by the Laboratory Veterinarian. Vater samples are periodically analyzed for total bacterial counts and for the presence of coliforms, lead, and other contaminants. Additionally, samples from freshly washed cages and cage racks are periodically analyzed to assure adequate sanitation by the cagevashers. Data from this program are maintained separately from study records. . Aniaal feed is certified by the manufacturer to meet specified nutritional requirements and to be free of a list of specified contaminants. On the basis of these analyses, there is no evidence suggesting that contaminants were present in the feed or vater in amounts which may have interfered with the results of this study. Rabbits were quarantined, weighed, and observed for general health for approximately 2 weeks. Animal rooms were maintained on a timer controlled, 12-hour light/12-hour dark cycle. Environmental conditions of the .rooms vere targeted for a temperature of 20"C 1*C and relative humidity of 501 + 101. Excursions outside these ranges were judged to have been of insufficient magnitude and/or duration to have adversely affected the validity of the study. B. Protocol On the day of treatment, the eyes of 2 female New Zealand Vhite rabbits vere examined using illumination, magnification, and fluorescein dye. Animals used on this study vere free of pre-existing corneal or Company Sanitized -4 - f-Coes ftn f nnf^ T S C A C ........ `--iiill> Durant KUt 271-5 tr-- f d ith .h. m U x ,,kb i t ..re rins.dfor.ppro,i..t.ly 1 water. The treated and control eyes of tlie reaa * g0 sccond8 washed. Each rabbit was J s v ^ d * a n y abnoroal behavior was noted. 2 * s 5 a t T S ,S i i 5 . ,S i 5 S : S * ? TM i11? l u ' u r a ! to be stab le under the co nd itio n s of a d n in is tr a t lo . Approxiaately 1 and 4 hours, and 1, * ; * u/<>s<n(chircd the rabbits were examined for evidence c - ay At each of these observation periods, eyes wer* illumination and magnification scored to the Dr.ize s c a l e ( PresentedinTable "^Urtl^ according observed for of the any unusual responses to -ff-cts indicative of corrosive action, conjunctiva, ulceration, or other effects indicarie toxicity at A d d it io n a lly , the ra b b its " . . . ^ I n ^ ^ c l l n l 1^ ^ , , each observation period. A He 0 f J rabbit. Control eyes ^ " o r ^ r ^ .'1 u n ! : . ^ eyes ere L a d fo r c p a r l s o n and era considered "normal" relative to the treated eye. C. Records Retention All rau data and th. final report ill be s j ^ o d in th. archives oi Management Center, Wilmington, Delaware. RESULTS H-210,5 produced uild conjunctival redness in the t r t ^ d . u n shed te. Hild conjnnotivil redness. slight/" d'after treatnent. the traatad ayes discharge were observed in CJ* *y* " fter instillation. No clinical signs ooff btootxhicirtaybbwiatsreweorbseernvoerdmadurying the stud.y. IInnddiivviidauuaali eeyyee irritation scores are presented in Tables 2 and 3. Company Sanitized. Does not contain TSC$ cctcuisiom ; - : [ Under the seditions of this study, 1-21095 was a slid, transieB&ig irritant. Si If thssa test scores are to be used for HC/0BCD classification, according to the guide to the labeling of dangerous substances publlsftfQ in the Official Journal of European Coenunitles (SEC Directive 93/21, Anne* VI), B-21095 probably could be classified as tfOM-ZEEXTANT" until further data is available. -s STB IRRITATION TEST VITH B-21095 TARLI 1 BRAIZE1 SCALE TOR SCORING OCULAR LESIONS a (I) Cornea (A) Opacity-degree of density (area aost dense taken for reading) No o p a c i t y .............. - ...................... 0 3 Scattered or diffuse area, details of iris clearly visible .................... . . . . . 1 (Slight) . Easily discernible translucent areas, details of iris slightly o b s c u r e d .......... ............ 2 (Mild) Opalescent areas, no details of iris visible, ! size of pupil barely discernible ............ 3 (Moderate) Opaque, iris invisible.......... ................ 4 (Severe) I (P) Area of cornea involved One quarter (or less) but not zero . . . . . . . . Greater than one quarter, but less than half . . . Greater than one half, but less than three q u a r t e r s ................ .. .................. Greater than three quarters, up to vhole area . . 1 (Localized) 2 (Snail) 3 (Moderate) A (Generalized) (2) Iris (A) Values N o r a a l ........ .................. ................ Folds above noraal, congestion, swelling, circuacorneal injection (any or all of these or combination of any thereof) iris still reacting to light (sluggish reaction is positive) . . . No reaction to light, hemorrhage, gross destruction (any or all of these) . . . . . . . 0 1 (Moderate) 2 (Severe) (3) Conjunctiva ' (A) Redness (refers to palpebral and bulbar conjunctiva excluding cornea and iris) Vessels noraal . . . . .......................... Q Vessels definitely injected above noraal ........ 1 (Mild) More diffuse, deeper criason red, individual vessels not easily d i s c e r n i b l e .............. 2 (Moderate) Diffuse beefy r e d .............. ................ 3 (Severe) tifi 7- Dttfoat BLR 271-95 ETE IRRITATION TEST OTTH H-22095 TABLE 1 (Coat'd) W A I 2 E SCALE FOR SCOKIHG OCULAR tjggTnMg (B ) Chemos is No s v e l l i n g ............................ Any swelling abo-e normal (includes nictitating * m e m b r a n e ) ................ Obvio"s sweliing with (artial eversion oi....... ^ ., flight) Svelling with'lids about half'closed i .' ! ! Svelling with lids about half closed to completely Clsed ........ .. ........ . . . . . (C) Discharge No discharge.................................. Any amount different from normal (does not include small amounts observed in inner canthus of normal a n i m a l s ).............................. Discharge with moistening of the lids and hairs * just adjacent to l i d s ......................... Discharge with moistening of the lids and hairs, and considerable area around the e y e ........ 3 iildJr-t.i A (Severe) q , ' 2 3 (Copious)1 1 ?rai2e! "Dermal Toxicity." Appraisal of the Safety of Chemical jn Foods, Drugs and Cosmetics. The ETitorial Coimittee of the Association 6-59? Snd offlcials of th United States, Austin, Texas, 1959, pp. Company Sanitized Does not contain T8GAGBI - 8- DuPont ILK 271.95 EYE IRRITATION TEST VIYH H-21095 TABLE 2 ETE IRRITATION REACTIONS OBSERVED IN IRE UNWASHED RABBIT ETE Rabbit Number 30019 Cornea Opaci ty Area Iris Conjunctiva Redness Chenosis Discharge 1 4 12 3 Hour Hours Day Days Days 0 0 00 0 0 0 00 0 00 . 10 00 00 00 00 00 00 0 o 0 0 "a- o M < Rabbit Nuaber 30020 Cornea Opacity Area 1 Hour 4 Hoars 00 00 Iris 00 Conjunctiva Redness Cheaosis Discharge 10 10 2H+ 0 H+ - Heaastix* evaluation positive for blood 1 --- 5---- -- J -- -- Day Days Days 00 00 0 C 00 0 00 00 00 0 0 0