Document Znokx43wjnb2r1ekL8EV3k8v8

AR226-2919 FOR DU FONT USE ONLY Copies to: Haskell E. I. du Pont de Nemours and Company Inc. Laboratory for Toxicology and Industrial Medicine Elkton Road, P. 0. Box 50 Newark, Delaware 19714 HASKELL LABORATORY REPORT NO. HLO-587-84 Haakell No. 15,588 Other Codes Study Initiated/Completed ------6/11/84 - 6/18/84---- Material 'olymer rrooucts Department Washington Works EYE IRRITATION TEST IN RABBITS Hsskell Evaluation; Haskell Standard Operating Procedure for eye irritation testing was followed] Is are given_jn the appendix* In the unwashed eye, conjurctival redness, _ flight _c_o_n_ju_n_ct_iv_a_l _c_he_m_o_s_is_, _with_clearino by seven days. In the washed eye,\ in------jproducedmild conjunctival redness with_clee produced moderate it corneal dullinc Its a moderate eye irritant. 'Composition; *,Synonyms; 1 - iCompany Sanitized. Does not contain TSCA CW Report by: Reviewed by: Carol S. Auletta/Donna L. Blaszcak Bio/dynamics Inc. George W. Lovett, M.D. Skin and Eye Studies Coordinator Gerald L.Kennedy flrj Section Supervisor / Acute Investigations Approved by: '^LJIQ.^. Frank A. Bower Associate Director GWL/egg Date Issued: August 30, 1984 Haakell Lab. Report No. HLO-3B7-B4 Appendix attached: 10 pp, Bio/dynamics Project No. 5227-84 Total pages in this report: 12 ^.^W^W- '^ - 2 rww^a'Vi .^,. r',1,.-.--^ - Bio/dynamicsInc. Division of Biology and Safety Evaluation PROJECT NO.: 5227-84 EYE IRRITATION STUDY IN RABBITS TEST MATEKIAL: HL 15,388 Submitted to: < Attn: E.I. du Pont de Nemours & Company Haskett Laboratory for Toxicology and Industrial Medicine Elkton Road, P.O. Box 5C Newark, Delaware 19711 Date: August 13, 1984 ^BCTpanySanitized. Does not conla'n -r^^ rw /dynamlcH Inr -15227-84 I. INTRODUCTION This study was conducted for E.I. du Pont de Nemours & Company to evaluate the ocular irritation produced by HL 15,388 in rabbits. The study was performed at Sic/dynamics, Inc., Mettlers Road, East Millstone, New Jersey 08873. This report has been reviewed by the Quality Assurance Unit of Sic/dynamics, Inc. to assure its conformance with the protocol and raw data. All raw data, the original study protocc1 and final report will be retained on file in the Bio/dynamics Archives. II. EXPERIMENTAL DESIGN No. Of Rabbits Amount of Material Eyes Washed/ Unwashed 10 mg 10 mg Unwashed washed III. DATES OF STUDY: Animal Receipt: Initiacion (Dosing): Termination (Last Observation): IV. STUDY PERSONNEL: Study Director: Laboratory Supervisor: Technician in Charge: Study Monitor (Report Preparation): V. STUDY CONDUCT VI. MATERIALS A. Test Animals: Breed; Reason for Selection: April 30, 1984 June 11, 1984 June 18, 1984 Carol S. Auletta, B.A., D.A.B.T. Donna L. Blaszcak, B.S., AALAS R.L.A.T. Mary Webb, B.S.. AALAS Deborah Metting, B.A. This study was conduc.ted following Good Laboratory Practices. Albino Rabbits New Zealand White Standard laboratory animal for ocular irritation studies. The New Zealand White breed was used because of its availability and because of the existing historical data base for comparative evaluation. ^SffipanySahIlizeaL Does hoi contain TSCA CBl /dynamics Inf. -25227-84 VI. MATERIALS (cont.) Supplier: Number: Hazleton-Outchland, Inc. Denver, Pennsylvania Two (2 males) Age: /oung adults Equilibration Period: Observations: Husbandry; 42 Jays All animals were checked for viability twice daily during the equilibration period. Prior to assignment to study all animals were examined to ascertain suitability for study. Currently acceptable practices of good animal husbandry were followed, e.g., Guide for the Care and Use of Laboratory Animals; PHEM Publication Mo. (NiH) 75-23 ftevised 1978. Housing: Individually housed Cages: Suspended, stainless steel Environmental Conditions: Temperature: 60-70*'? is considered an acceptable temperature range for rabbits; room temperature was monitored and recorded twice daily and maintained within this range to the maximum extent possible. Humidity: 30-702 is considered an acceptable humidity range for rabbits; room humidity was monitored and recorded daily and maintained within this range to the maximum extent possible. Light cycle: 12 hours light, 12 hours dark (controlled by an automatic timer) Food: Hater: Lab Rabbit Chow HF (Purina #5326), ad libitum Automatic watering system, ad libitum Municipal water supply (Elizabethtown Mater Co.) Does not contain T8CA Cffl , ----_ /riyoamlcw Inc -3- 5227-84 V. MATERIALS [cont.) Identification: Selection: Each animal was identified with a mone1 ear tag bearing a unique number prior to testing. Animals were randumly placed in cages upon receipt and were placed on study as available at the time of study Initiation. Animals considered unsuitable for study because of poor health or ocular abnormalities were excluded from selection. VII. B. Test Material: Description: Date of Receipt: Received from: Storage: METHODS HL 15,388 White powder May 21, 1984 E.I. du Pont de Nemours & Company Room temperature A. Duration of Study: A single dose was administered followed by a 3 to 7 day observation period. B. Route of Administration: Ocular C. Justification for Route of Administration: The study is intended to provide information on the health hazards likely to <xrise from a short-term accidental exposure to the test material by the ocular route. 0. Preparation of Animals: On the day ;efore dosing, both eyes of each animal we'-e examined using fluorescein dye to check for presence of corneal ulceratibn. Just prior to test substance application, the eyes were examined again, but without fluorescein. Animals showing pre-existing corneal or conjunctiva! injury or Irritation were not placed on study. E. Preparation of Test Material: The test material was administered as received; no mixture was required. CompanySanitized. Does not contain TSr'a f.m /dynamics Inf. -45227-84 VII. METHODS (cont.) F. Administration of Test Substance: 1. Dose: 10 mg 2. Adnrini strati on: The appropriate amount of the test material was introduced into the lower conjunctiva! sac of the right eye of each animal. The upper and lower lids were gently held together for one second prior to releasing to prevent loss of material. The contra!ateral eye served as the control. 3. Hash: The treated and control eye of one animal remained unwashed. Twenty seconds after the test substance was administered, both eyes of the remaining animal was rinsed for one minute with lukewarm water. VIII. EXPERIMENTAL EVALUATION A. Viability Check: Twice Daily B. Evaluation of Ocular Irritation: 1. Intervals: Approximately 1 and 4 hours and 1, 2, 3 and 7 days after treatment, or until no signs of Irritation were present. 2. Methods: At each interval the treated and control eyes were examined and scored for ocular reactions according to the Draize scale (see Appendix A). Fluorescein dye was used to confirm presence or absence of cornea! ulceration in treated eyes starting with the 24 hour observation and at each subsequent observation. Unusual effects such as pannus, blistering of the conjunctiva, ulceration and other effects indicative of corrosive action were also noted when present. Company Sanitized. Does not contain TSCA CB1 /dynamics Inr. -5- 5227-84 IX. RLSuLTS AND DISCUSSION Individual ocular observations are presented in Table I; the scoring system used is presented in Appendix A. A summary of 1) responses considered positiv .iccording to 16 CFR 1500.42 [CONSUMERPRODUCT SAFETY COMMISSION, Federal Hazardous Substances Act Regulations, Test for Eye Irritants] and 2) Maximum Draize Scores is presented in Table II. HL 15.388 produced mild but reversible ocular irritation in both the washed and unwashed eyes. Both eyes had mild to moderate conjunctival irritation (redness, chemosis) and slight corneal and/or iridial changes. Both of the animals were free of ocular irritation within 3 to 7 days after instillation of the test material. Responses in the non-rinsed eye were similar to those in the rinsed eye. Therefore, rinsing of the eye after instillation of the test material did not appear to have had a beneficial effect. ^._______ C ^...... Carol S. Auletta. B.A.. D.A.B. Study Director Manager, Acute Toxicology ^ H 5ate ^V/- ^ ^ate------ i^fflpahy Sanitized. Does not con??'" TRCA CBf -6- 5227-84 KEY TO FOOTNOTES Scores given are for treated eyes. Unless otherwise noted, control (untreat ed) eyes had negative scores for all parameters. Scored according to Drai'ze Scale presented in Appendix A. *Twenty seconds after dosing, both eyes were rinsed with lukewarm water for one minute. f-Observation confirmed with fluoresceln. M-Male F-Female [CompanySanitized. Does not conlain TSCA CBT -1- 5227-84 TABLE I EYE IRRITATION STUDY IN RABBITS Animal No. 38"3 H 1. Conjunctivae A. Redness B. Chemosis C. Discharge D. Necrosis(N)/ UlcerationdJ) Score 2. Iris Score TEST MATERIAL: HL 15.388 INDIVIDUAL OCULAR SCOR^ Tline After Admi mstr atlon Ho urs 4 )ay s 1 T' 3 7 1 1 1 2 0 0 0 0 4 6 0 0 0 0 2 1 1 0 1 1 0 0 0 0 0 0 0 0 0 0 6 4 2 0 0 0 0 0 0 p 0 0 p'ositive Score 2'4, 48, 72 Hr. ( per 16 CFR 1500.42) Yes No No No 3. Cornea A. Opacity + + 0 0 0 0 No B. Area 2 2 0 0 0 0 C. Stippling 2 2 0 0 0 0 D. UUeration 0 0 Of Of Of Of No Score 0 0 0 0 0 0 Other - - - - - - Total Score 4 6 6 4 2 0 Animal No. 3899 M* 1. Conjunctivae A. Redness 1 1 1 1 0 No B. Chemosis 1 1 0 0 0 No C. Discharge 0 0 0 0 0 D. Necrosis(N)/ 0 0 0 0 0 No Ulceration(U) Score 4 4 2 2 0 2. Iris Score + 0 0 0 0 0 0 0 0 0 No 3. Cornea A. Opacity 0 0 0 0 0 No B. Area 0 0 0 0 0 C. Stippling 1 0 0 0 0 0. Ulceration 0 0 Of Of Of No Score 0 0 0 0 0 Other - - - - - Total Score 4 4 2 2 0 Key to footnotes presented on page 6. PJmpanySanitized. Does hot contain TSCA CB1 TABLE II EYE IRRITATION STUDY IN RABBITS TEST MATERIAL: HL 15,388 SUMMARY OF RESPONSES AND MAXIMUM DRAIZE SCORES -8- 5227-84 Positive () or Negative (-) Scoresa____ Maximum Draize Score Animal ___Cornea___ Iris ____Conjunctiyae Necrosis or Number Opacity Ulceration Redness Cheinosis Ulceration Score! First Time Obtained Time Clear^ Unwashed M- - - + - 64 3893 Mashed 3899 M - Hour Day 7 4 1 Hour Day 3 reference for positive and negative scores (24, 48 and 72 hours): 1. 16 CFR 1500.42 i. (IUll.uSs. trGaotveedrnmGuenidte Pfroinr tiGnrgadOinfgficEeye, WIrarsithaintgiotonn, byD.CH.aza0rd2o4u02s) Substances. ^ime clear is time that eye was free of all irritation. company Sanitized. Does not conta?n TSCA Appendix A , Sfndard Eye Irritation Grading Scale' I. CORHEA VALUE A. Opacity - degree of deailty (area mst dm* .taken for rttding) NSoligOhtpdauclliintgy.o.f!.n.o..rn..^.l .............................................. 0 ** Scattered or diffuse ri1f uof*otpirc.t.t.y..(.o.t.h.e..r..t.h.i.n..i.l.l.l.h..t..d.u..ll.i.n.g.... of nonul luster), details of Iris clearly visible............... 1 * Easily discernible translucent areas; dftilU of lr( (lightly Oopable*i cCBunrt adre. a..s.,. .n.o. . .d.a..t,f .l l.s.. .o.f. . .I r. .i s.. .v..l.t i l b. l. e.. >s..i z e .o.f. .p.u.p. i.l . . . . . . . . 2 * barely dliern1b1*................................................ 3 * * * Opaque, Iris Invisible....................................... B. Total are* of corn** lBvo1ed: (Total area exhibiting ny opacity, regardless of degree;------------T------ One quarter (or 1eill but Greiter then one quirttr, not but IZts*roth.*.n..h....K............................................... 1 2 Greater Greater than than half, three but qua 1 ess rtcn , t hin up t three o who l e q uirtcn. re*.... . . . . . . . . . . .............. ............. 3 4 Corneal Score2: A X B X 5 (Haxlir Score 80) C. Stippling - (ppeannct of pinpoint roughening)** No' 0 OnesqtutaprtperT(ionr gle.s.s..)..b.u.t..ni.o.t..z.e..r..o.................................................................... 1 Greater ereater than than honaelfq. ubaurttelre,ssbutthalenssthrteneinqhuaalrft.e..r.i....................................... 2 3 Greater than three quarters, up to whole area...................... 4 0. Ulceratlon (absence of a gross patch of comet) epithelliml** BOnoe TquTaerteerrS(oTr lloesns.)..b..u.t..n.o.t............................................ 0 1 * Greater than one quarter, but zleessroth.a.n...h...1..f.............................................. 2* Greater Greater than than half, three but:1ess than three quarters.................... quarters, up to whole 3 * * * erea...................... II. IRIS A~~Va1ues HSliogrhwt daee'\p.e.n.i.n.g..o.f..t.h..t..ru..g.a.e..o.r..s..l.ig..h.t..h..y.p.e.r.w..il.a..o..f..th..e............ 0 Hcalrrkceudlcyomdeeeap1enebdloofod1vd(ts(bieoles.n.o..m..a.l.),...c.o.n.g.e..s.ti.o.n.,...s.w..e.ll.i.n.g.,....... * cIreuRcorneal injection (any or all of these or cooblnatlon of any thereof). 1r1s still reacting to light (sluggish Norearecaticotnion1stopoligshitt,ivheen)o,r.r.t.i.ig.*.,..g..ro..s.s..d.e..s.t.r.u.c.t.io..n...(a.n..y..o.r..a..ll..... l * of these)............^............................................ 2 Iris Score2: A X f (Haxinuu Score 10) III. COmUHCTlVAE 'S~.Keeness (refers to palpebral and bulbar conjunctlvie excluding cornea and Iris) VSoemsesevlsesnseelsrodeafiln.i.t.e.l.y...In..je.c..te..d..a.b.o.v.e................................ 0 1 Diffuse, crimson red, individual vesselsnonortweia.s.i.l.y..d..is..c.e..r.n.i.b.l.e........ 2 B. Diffuse beefy Chwosis red.................................................. 3 AHOnytsuweellllilnng gab..o.v.e..n.o..r.la.1l .(.In..c.l.u.d.e.s...n.i.c.t.i.t.a.t.i.n.g...i.--..b..r.a..n..e.l................... o 1 Obvious swelling with bartlal Swelling with lids abobt half eers1on of lids..................... 2 3 * Swelling NIUI lids ore than hcallfocsleods.e..d....................................................... 4 C. Discharge AMnoy (mUolucnHt idriaffeBre..n.t..f.r.o..*..n.o.r.a.a.l..(.d.o..e.s..n.o..t..In.c..lu..d.e..S..M..i.l..f.o.u..n..t!.... 0 observed Discharge wInithinonBerlscteennfjcinhugsoof fthneolmidisaanndiuhlasir)s..J.u.<st..a.d.j.a.c..e.n.t..t.o.... 1 Dlisicdhsar.g.e..w..it.h..M..o.i.s.t.e.n.i:n.g..o.f..t.h.e..l.i.d.s..e.n..d..h.a.i.r.s..a.n.d..c.o.n.s..id.e..ra..b.le.... 2 area aroi i w......................^............................ l D. Necrosis or Ulceratlon' of palptbral and bulbar conjunctlvi* or nictitating mbnn* NNeoct rposrisatent........................................................ 0 N * Uleeratlonprpresnetn.t................................................................................................... l) * Conjunetlvie Score2: (A * I * C) X 2 i^irua Seer* 20) 'Oralze. J.H. 1959. The Xpprals-': of Ch--icals IR Foeds. Drugs, ind Cosmetics, p. 51. Assoelktion of Food and Drug Officials of the United States. Auxtln. Te&as. Total Drain score Is the su> of the three scores ebtalned (eome*, Iris, conjunctiva*). Score eonstdered positive; under 16 CrX 1500.42 Not Included In Dralte dfiading iyit--, values assigned If finding present. A-1 5227-84 ISBBpanySanWzed. Uoes Hot contain TSCA cm