Document 3Jp10dd8pkQdYdKG7bRxY9gBJ

AR226-3128 DuPont-3268 TRADE SECRET Study Title H-24119: Skin Irritation Test in Rabbits Laboratory Project ID: DuPont-3268 AUTHOR: Carol Finlay, B.A. Study C o m pl e t e d o n : July 30,1999 P erform ing L a bo r a t o r y : E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 W ork Request Number Service C ode Num ber Page 1 o f 12 Company Sanitized. Does not contain TSCA CBf H -24119: Skin Irritation Test in Rabbits DuPont-3268 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of the data obtained from this study. Reviewed by: TO Anne Marie Bathon, B.A. Senior Staff Scientist Issued by Study D irector:______ f /M C %J CarofFinlay, B .A fj Assoicate Scientist "'ompany Sanitized. Does not contain TSCA CBi -2 - H -24119: Skin Irritation Test in Rabbits DuPont-3268 TABLE OF CONTENTS Page CERTIFICATION........................................................................................................................ 2 STUDY INFORMATION............................................................................................................ 4 STUDY PERSONNEL.................................................................................................................. 5 SUMMARY....................................................................................................................................6 INTRODUCTION..........................................................................................................................7 MATERIALS AND METHODS..................................................................................................7 A. Test Substance.................................................................................................................... 7 B. Animal Husbandry.............................................................................................................. 7 C. Protocol................................................................................................................................8 RESULTS AND DISCUSSION....................................................................................................8 CONCLUSIONS............................................................................................................................9 RECORDS AND SAMPLE STORAGE......................................................................................9 TABLES........................................................................................................................................10 1. DRAIZE SCALE FOR SCORING SKIN IRRITATION........................................................11 2. INDIVIDUAL SKIN IRRITATION SCORES AND SKIN RESPONSES OBSERVED IN RABBITS...................... 12 Company Sanim,. Does Mnla)n ^ ^ -3 - H -24119: Skin Irritation Test in Rabbits STUDY INFORMATION Svnonvms/Codes: H-24119 Haskell Number: 24119 DuPont-3268 Stability: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed. Sponsor: E. I. du Pont de Nemours and Company Wilmington, Delaware 19898 U.S.A. Study Initiated/Completed: July 10, 1999 / (see report cover page) In-Life Initiated/Completed: July 13, 1999 / July 16, 1999 Company Sanitized. Does not contain TSCA CB! -4 - H -24119: Skin Irritation Test in Rabbits STUDY PERSONNEL Study Director: Carol Finlay, B.A. Management: Judith C. Stadler, Ph.D. Primary Technician: Carol Finlay, B.A. Toxicology Report Preparation: Amy L. Williamson Laboratory Veterinarian: Wanda L. West, D.V.M., A.C.L.A.M. DuPont-3268 Company Sanitized. Does not contain TSCA CB1 -5 - H -24119: Skin Irritation Test in Rabbits DuPont-3268 SUMMARY H-24119 was evaluated for acute skin irritation potential in 5 male New Zealand White rabbits. Approximately 0.5 mL of the test substance was applied to the shaved, intact skin of each rabbit and covered with a semi-occlusive dressing for a 4-hour exposure. Approximately 1, 24, 48, and 72 hours after removal of the test substance, the test sites were evaluated for erythema, edema, and other evidence of dermal effects and were scored according to the Draize Scale. The adjacent areas of untreated skin were used for comparison. No erythema was observed in 4 rabbits and mild erythema was observed in 1 rabbit at 1 and 24 hours after test substance removal. At 48 and 72 hours, 3 rabbits exhibited no erythema, 1 exhibited slight erythema, and 1 exhibited mild erythema. Desquamation was observed in 1 rabbit at 48 hours and in 2 rabbits at 72 hours. No edema was observed during the study. Under the conditions of this study, H-24119 was a mild skin irritant. Company Sanitized. Does not contain TSCA CBI -6 - H -24119: Skin Irritation Test in Rabbits DuPont-3268 INTRODUCTION The purpose of this study was to evaluate the skin irritation potential of H-24119 when applied to the shaved, intact skin of New Zealand White rabbits. MATERIALS AND METHODS A. Test Substance The te^t substance, H-24119, was supplied by the sponsor as al th e test substance was inverted to mix before each amount for dosing was removed. The tesFsubstance appeared to be stable under the conditions of the study. No evidence of instability, such as a change in color or physical state, was observed. B. Animal Husbandry Young adult HM:(NZW)fBR New Zealand White 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 was recorded on a card affixed to the cage. The last 3 digits of the identification number were written on the inside of each rabbit's ear with a water insoluble marker. The rabbits were offered approximately 125 grams of PMI Nutrition International, Inc. Certified High Fiber Rabbit LabDiet 5325 daily during the study. Water was available ad libitum except during the exposure period while the animals were in stocks. Haskell Laboratory has an animal health monitoring program. This program is monitored and administered by the Laboratory Veterinarian. Water 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 ensure adequate sanitation by the cagewashers. Data from this program are maintained separately from study records. Animal 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 water in amounts which may have interfered with the results of this study. Rabbits were quarantined, weighed, and observed for general health for 11 days. 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 1C and relative humidity of 50% 10%. Excursions outside these ranges were judged to have been of insufficient magnitude and/or duration to have adversely affected the validity of the study. Company Sanitized. Does not contain TSCA CBI -7 - H-24119: Skin Irritation Test in Rabbits DuPont-3268 C. Protocol On the day prior to treatment, the hair of 6 male New Zealand White rabbits was closely shaved to expose the skin from the scapular to the lumbar region of the back. The body weights of the rabbits ranged from 2423 to 2800 grams on the day of treatment. Each rabbit was placed into a stock which had been fitted with a piece of rubber sheeting, approximately 8" x 18". The rabbits remained in the stocks throughout the exposure period and during that time did not have access to food or water. Approximately 0.5 mL of H-24119 was applied directly on the skin beneath a 2-inch gauze square that was held in place with non irritating tape. The rubber sheeting was then wrapped around the animal and secured with clips to retard evaporation and to keep the test substance in contact with the skin without undue pressure. One other test substance was tested concurrently on a separate, localized test site on the backs of these rabbits. Approximately 4 hours after application of the test substance, the rubber sheeting was loosened, and the skin at the comers of the gauze squares was marked with a waterproof pen; wrappings and gauze squares were then removed. The test sites were gently washed with warm water to remove excess test substance. The skin was gently patted dry, and the animals were returned to their cages. Approximately 1, 24, 48, and 72 hours after removal of the test substance, the test sites were evaluated for erythema, edema, and other evidence of dermal effects and were scored according to the Draize Scale (Table 1). The adjacent areas of the untreated skin were used for comparison. One rabbit was removed from the study because the rabbit exhibited dermal irritation on and outside the test site. This dermal irritation was believed to be due to shaving abrasions. The rabbits were also examined for clinical signs of toxicity at every dermal evaluation. The rabbits were weighed on the day of treatment and at the last dermal evaluation. RESULTS AND DISCUSSION No erythema was observed in 4 rabbits and mild erythema was observed in 1 rabbit at 1 and 24 hours after test substance removal. At 48 and 72 hours, 3 rabbits exhibited no erythema, 1 exhibited slight erythema, and 1 exhibited mild erythema. Desquamation was observed in 1 rabbit at 48 hours and in 2 rabbits at 72 hours. No edema was observed during the study. One rabbit exhibited weight loss of approximately 2% of initial body weight by study termination (72 hours). Individual skin irritation scores are presented in Table 2. A summary of skin responses is presented in the following table. Company Sanitized. Does no! contain TSCA CBf -8 - H -24119: Skin Irritation Test in Rabbits DuPont-3268 SUMMARY OF SKIN RESPONSES TO H-24119 RESPONSE No Response Slight Mild 1 4/5 0/5 1/5 HOURS AFTER TEST SUBSTANCE REMOVAL ERY1HEMA EDEMA 24 48 72 1 24 48 4/5 3/5 3/5 5/5 5/5 5/5 0/5 1/5 1/5 0/5 0/5 0/5 1/5 1/5 1/5 0/5 0/5 0/5 72 5/5 0/5 0/5 CONCLUSIONS Under the conditions of this study, H-24119 was a mild skin irritant. If these test scores are to be used for EEC/OECD classification, according to the guide to the labeling of dangerous substances published in the Official Journal of European Communities (EEC Directive 93/21, Annex VI), H-24119 probably should not be classified as an irritant unless further data proves otherwise. RECORDS AND SAMPLE STORAGE Specimens (if applicable), raw data, and the final report will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware (formerly known as the E. I. du Pont de Nemours and Company Records Management Center). Company Sanitized. Does not contain TSCA CB! -9 - H-24119: Skin Irritation Test in Rabbits DuPont-3268 TABLES Company Sanitized. Does not contain TSCA CBI - 10- H-24119: Skin Irritation Test in Rabbits DuPont-3268 TABLE 1 DRAKE3SCALE FOR SCORING SKIN IRRITATION Evaluation of Skin Reactions Score Erythema and eschar formation: No erythema.............................................................................................................0 Very slight erythema (barely perceptible).............................................................. 1 (Slight) Well-defined erythema.............................................................................................2 (Mild) Moderate to severe erythema................................................................................. 3 (Moderate) Severe erythema (beet redness) to slight eschar formation (injuries in depth)...... 4 (Severe) Edema formation: No edema.................................................................................................................0 Very slight edema (barely perceptible).................................................................. 1 (Slight) Slight edema (edges of area well defined by definite raising).................................2 (Mild) Moderate edema (raised approximately 1.0 m m ).................................................. 3 (Moderate) Severe edema (raised more than 1.0 mm extending beyond the area of exposure).......................................................................................................... 4 (Severe) Abbreviations of other dermal effects are: - = No Effect I = Intact A = Abraded L = Sloughing B = Blanching N = Necrosis C = Eschar R = Raw Areas D = Desquamation S = Epidermal Scaling F = Fissuring T = Thickening G = Fissuring with Bleeding X = Compound Adhered to Skin H = Hyperkeratosis a Draize, J. H., "Dermal Toxicity." Appraisal o f the Safety o f Chemicals in Foods. Drugs and Cosm etics The Editorial Committee o f the Association o f Food and Drug O fficials o f the United States, Austin, Texas, 1959, pp. 46-59. `otttpany Sanitized. Does not contain TSCA CBI -11 - H -24119: Skin Irritation Test in Rabbits DuPont-3268 TABLE 2 INDIVIDUAL SKIN IRRITATION SCORES AND SKIN RESPONSES OBSERVED IN RABBITS RABBIT NUMBER 33816 33821 33826 33831 33839 HOURS AFTER TEST SUBSTANCE REMOVAL ERYT]SEMA EDEMA 1 24 48 72 1 24 48 72 22 1 10 00 0 0000 000 0 000 0000 0 00220000 00000000 RABBIT NUMBER 33816 33821 33826 33831 33839 HOURS AFTER TEST SUBSTANCE REMOVAL OTHE R DERMAL EHFECTS 1 24 48 72 D- - - ---- - --- - - DD - - -- Symbols are defined in Table 1. Company Sanitized. Does not contain TSCA CBl - 12-