Document QJwvbZmzLwpk06bRG01MBZkJR

AR226-2988 Study Title ~ Eye Irritation Test with H-19913 in Rabbits Author John V. Server Study Completed On March 10, 1993 Performing Laboratory E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medieirte Elkton Road, P. 0. Box 50 Newark, Delaware 19714 Medical Research No. Laboratory Project ID Haskell Laboratory Report No. 865-92 Page 1 of 12 PlB|saiigSanitized. Does notcontain TSCA CBI P *1 'Hi!: Du Pont HLR 885-92 GOOD LABOBATQRY PB A C H G B COMPLIANT STATEMENT This study as conducted according to SPA TSG& Good Laboratory Practice Standards (40 CFR 792). toy areas of noncompliance are documented in the study records, to deviations existed that affected the validity of the study. Submitter: E. I. du Pont de Nemours and Company Sponsor: Du Pont Chemicals B. I. du Pont de Nemours and Company Study Director: John V. Server Toxicologist 3 /So/i^ -2- Company Sanitized. Does not contain TSCA CB1 Substw e e Tested: Syao nys/Q xies : Physical Fora; Composition: Purity: Submitter's Notebook No. CAS R egistry Ho.: Du Pout Slit 885-92 GENERAL INFORMATION (CONT'O.) CAS Resigtry No. (Coat'd.): Sponsors Study Initiated - Completed; In Life Phase Initiated - Coapleted: 12/14/92 - 3/10/93 12/15/92 - 12/18/92 -4 - Sanitized. Poes not coniam T3CA CB| Du Pont BLR 885-92 Eye Irritation Test vitti B-19913 in Rabbits SUMMARY B-19913 was evaluated for acute eye Irritation potential in 2 rabbits. Approximately 0 .01 b L of the test substance vas instilled into the lover conjunctival sac of the right eye of each rabbit. Approximately 20 seconds after instillation, the treated and control eyes of 1 rabbit were washed. The treated- and control eyes f the remaining rabbit were not washed. The eyes of the rabbits were examined on the day of treatment and on d a y s 1, 2, and 3 following treatment. B-19913 produced moderate conjunctival redness in both treated rrabbit eyes. The treated washed and unwashed eyes were normal by 2 and 3 days, respectively, following treatment. Under the conditions of this study, H-19913 was a moderate eye irritant. Reviewed and Approved for Issue JVS/lsr t Tracy A. Filliben Toxicology Technician John W. Sarver Study Director 3 /io ^ 3 -5 J^rogany Sanitized. Poes not contain iSCACBI '7/'T';*.'v j. DuPont H L R 885-92 Q M U m ASSURANCE DOCUMENTATION (H-19913) Pares of Inspection: Conduct - Decenber 15, 1993 Records, Report(s) - February 25, 1993 March 1, 2, 1993 Date(s) Findings Reported to: Study Director - March 2, 1993 Management - March 4, 1993 Reported by: I'. 3 .. Linda S. Mau Quality Assurance Auditor rV# Date -6Company Sanitized. Does not contain TSCA CEI INTRODUCTION Du Pont HLR 885-92 The purpose of this study vas to evaluate the acute eye irritation potential of B-19913 in young adult rabbits. This study was conducted according to the applicable SPA Good Laboratory Practice Standards- Areas of noncoapliance are documented in the study records. No deviations existed that affected the validity of the study. MATERIALS AND METHODS A. Animal Husbandry Young adult sale New Zealand White rabbits were received f r o m Hare Karland, Hewitt, New Jersey. The rabbits were housed singly in suspended, stainless steel, wire-mesh cages. Each rabbit was assigned a unique identification number which was recorded on a card affixed to the cage. The rabbits were offered 125 grams of Purina Certified H i g h Fiber Eabbit Chow #5325 daily during the study. Water was available ad libitum. 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 were targeted for a temperature of 20C 2C and relative humidity of 502 102. Excursions outside these ranges were judged to have been of insufficient magnitude and/or duration t o have adversely affected the validity of the study. ` B. Protocol On the day of treatment, the eyes of 2 male New Zealand W h i t e rabbits were examined using illumination, magnification, and fluorescein dye. These animals were selected for this study as they showed no evidence of preexisting corneal or conjunctival injury or irritation and w e r e judged to be in good health. These rabbits weighed 3185 or 2737 grams o n the day of treatment. Approximately 0.01 mL of H-19913 was introduced into the l o w e r conjunctival sac of each right eye. The left eye of each rabbit was not treated with the test substance and served as a control. Approximately 20 seconds after the test substance was administered, both eyes o f 1 rabbit were rinsed for approximately 1 minute with room temperature water. The treated and control eyes of the remaining rabbit were* not washed. Each rabbit was observed for approximately 30 to 60 seconds before being returned to its cage and any abnormal behavior was noted. In the absence of visible evidence to the contrary, the test subs tance was assumed to be stable under the conditions of administration. -7jgprapang Sanitized. Does not contain TSCA CEI !V-- Du Pont HLR 885-92 Approximately 1 and 4 hours, and 1 2, and 3 days after B-19913 was administered, the rabbits were examined for evidence of eye irritation. At each of these observation periods, eyes were examined using illumination and signification and scored for ocular reactions according to the Draize scale (presented in Table 1). Eyes were also observed for any responses to treatment such as pannus, blistering o f the conjunctiva, ulceration, or other effects indicative of corrosive action. Control eyes were not scored. These untreated eyes were used f o r comparison and were considered "normal" relative to the treated eye. C. Records Retention 3H ry data the final report will be stored in the arehives of EisfeelT laboratory fox Toxicology-and Industrial Medicine, E. I . du Pont de Nemours and Company, Newark, Delaware or in the Du Pont Records Maitageeent Center, Vilmington, Delaware. RESULTS H-1991? produced moderate conjunctival redness in both treated rabbit eyes. The t reated washed and unwashed eyes were normal by 2 and 3 days, respectively, following treatment. Individual eye irritation sco r e s are presented in Tables 2 and 3. CONCLUSION Under the conditions of this study, H-19913 was a moderate eye irritant. ^ f 4htsci&bi t>CC^C5 to bi- nn th7 ranponifiB nbsurireit fn liii'i1 -for c.ri^lOep> sod according to the guide to T h i T e b e l i n g of dangerous substances published in the Officiaf^Jouraal of European Communities (EEC Directive 83/467, Annex VI), H-19913 probably could be classified as a "NON-IRRITANT" until further data is availablIee.j1 V ,./ hCiu- * Ofiri \ - 8 - Company Sanitized, Does riot contain TSCA CBI THHT .. mmm Du Pont BLR 885-92 1 DRAIZE1 SCALE FOR SCOEIHG OCULAR LESIONS W5PW (I) Cornea . (A) Opacity-degree of density (area most dense [ taken for reading) No opacity ...................................... 0 Scattered or diffuse area, details of iris clearly visible ................... . . . . . . Easily discernible translucent areas, details of 1 (Slight) ' iris slightly o b s c u r e d ..................... . 2 (Mild) Opalescent areas* no details of- iris visible, size of pupil barely d i s c e r n i b l e ............. Opaque, iris invisible ............................ 3 (Moderate) 4 (Severe) (B) 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 (Small) 3 (Moderate) 4 (Generalized) )' ` (2) Iris (A) Values Normal ............................. ............. Folds above normal, congestion, swelling, circum- 0 corneal injection (any or all of these or combination of any thereof) iris still reacting to light (sluggish reaction is positive) . . . 1 (Moderate) No reaction to light, hemorrhage, gross destruction (any or all of these) ............. 2 (Severe) (3) Conjunctiva (A) Redness (refers to palpebral and bulbar conjunctiva ' excluding cornea and iris) ' Vessels normal . . . . . . . . . . . . . ........ Vessels definitely injected above normal ........ (Mild) More diffuse, deeper crimson red, individual vessels not easily discernible . . . . . . . . Diffuse beefy red ................................ 2 (Moderate) 3 (Sev-ere) Ssmgan^Saoiiized. Does not comsui ibCACBi Du Pont BLR 865-92 TABLE 1 (Cant'd) DBAZZB SCALE FOR SCQRIMG OCULAR LESIONS (B) Cheaosis Ho s w e l l i n g ................................. .. Any swelling above noreal (includes nictitating aeabrane) ................... .................. Obvious swelling with partial eversion of l i d s ............................. Swelling vith lids about half c l o s e d ............ Swelling with lids about half closed to coapletely c l o s e d ................................. .. . . 0 1 (Slight) 3 (Moderate) 4 (Severe) 2 (Mild) (C) Discharge Mo discharge . . . ................................. 0 Any anount different froa noraal (does not include snail aaounts observed in inner can thus of noraal a n i a a l s ) ................................. 1 (Minimal) Discharge vith aoistening of the lids and hairs just adjacent to l i d s ........................... 2 (Moderate) Discharge vith aoistening of the lids and hairs, and considerable area around the e y e ........ 3 (Copious)1 1 Draize, J. B., "Dermal Toxicity." Appraisal of the Safety of Cheaticals in Poods, Drugs and Cosmetics. The Editorial Conaittee of the Association of Food and Drug Officials of the United States, Austin, Texas, 1959, pp. 46-59. - 10 - jCampMf Sanitized. Does not contain TSCA CBI Du Font S B l ^ .. , y- EYE HEITATKW REACTIONS OBSERVED IN THE UNgASBBP RBlIT EYE AFTBR TRMIIffiRT ITH H-19913 885-92 RaUdt Bober 27590 Cornea Opaeity Area Iris Conjunctiva Redimas Claesesia Discharge 1 Hour 0 0 0 4 Bours-v.' 1 Day 00 00 00 2 Days 0 0 0 3 Days 0 0 0 2 2 11 0 0 0 00 0 0 0 00 0 Company Sanitized. Does not contain TSCA CB1 Du Pont HI& 885-92 TABUS 3 E m wsaxuaas r e a c o n s JL,, WASHED RABBIT 8E AFTER TlEAfHBiT lSg H-19913 Conjunctiva Sadness Chenosis Discharge I l 10 0o Uo 0o 0 0 - 12 - SLompaifSanitized. Does notcontain TSCA CBI