Document Xz5J3ZDxnYeJrpr7L1YVZK1Rd

AR226-2981 DU PONT HLR 879-92 HASKELL LABORATORY FOR TOXICOLOGY AND INDUSTRIAL MEDICINE STATIC. ACUTE 96-HO UR SCREENING TE ST O F H-19913 TO FATHEAD MINNOW S. Pim ephales prom elas DISCLAIM ER: TH IS STUDY W AS NO T CONDUCTED ACCORDING TO FO R M A L REGULATORY GOOD LABORATORY PRACTICE STANDARDS. GENERAL INFORMATION MATERIAL TESTED: PURITY: COM POSITION: Poly(difiuoromethylene), aipha-fluoro-om ega-[2((2-m ethy-l -oxo-2-propenyl)oxy]ethyl]-, polym er with 2-ethyfhexyl 2-propenoate, 1.1-dichloroetfiene. 2-hydroxyethyi 2-methyt-2-propenoate. N (hydroxymethyl)-2-propenamide, and a lp h a -(2 methyI-1 -oxo-2-propenyl)poly(oxy-1,2-ethanediyl) Sponsor: Notebook ID: SUMMARY H -19913 toxicity was low (96-hour LC50 between 500 to 5000 mg/L) in a 9 5 -hour unaerated, static, acute test using fathead minnows, Pim ephales prom elas. Nominal concentrations of H-19913 tested were 0 ,0 .5 0 ,1 .0 , 50, 500, and 5000 m g/L. Mortalities of 0 , 0 , 0 , 0 , 0 , and 100%, respectively, were observed. Based o n visual observations, the test substance was soluble in well water at 0.5 and 1.0 m g /L . The three highest test concentrations appeared cloudy. Dissolved oxygen and p H were measured in 0 ,0 .5 , 50 and 5000 mg/L nominal concentrations. The dissolved oxygen at 0 and 96 hours or at total mortality were 8 .5 ,8 .5 ,8 .6 and 8.5 mg/L and 9 .0 , 8 .7 ,8 .4 and 0 .7 mg/L, respectively. The lowest dissolved oxygen value resulted fro m the decomposition of dead fish at 5000 mg/L. The pH values at 0 and 96 hours c?r at total mortality were 7.0, 7.1, 7.2 and 7.2 mg/L and 7.5, 7.7, 7.7 and 7.0 mg/L, respectively. Company Sanitized. Does notcontain TSCA C l| WORK BY: DU PONT HLR 879-92 t !<s m o /day/ y e a r APPROVED BY: A w . C > \M & ~ GUAT-UAN C. KREAMER RESEARCH TOXICOLOGIST M O /D m YEA R D IS T R IB U T IO N : K. DASTUR(1) W .J . BROCK (1) E L HOLLOWAY (1) R. V. DAUM (1) G .C . KREAMER (1) '-Siili (Sompany Sanitized. Does not contain TSCA CHI (to Pent HIA 21-93 fhi atudy w oeodnetad iooardlfiv IfA H TSC4 Coed laboratory Praetlea Standard (40 CP* 7f3>. Any rata of oeoeeapl.1 ara deeuaantad In the *tidy raeord. No deviation iitflti that affected tha validity of tha atudy. SutMlttai! I. I, Pent da Honour and Conpany Sponaerji On Pont Oieaieal 0 1. do Pont da Neuour* and Ceapany Study Piraetort JasKL J U .& m Sarvor loxicoloslat iampapf Sanitized. Does not contain TSCA CBI ah^cin.^-M Substsisee Tested c m b u u .iw G B m m m Du toast II* 2-t3 1 Synonyua/Codaga Physical Wvm% Composition! Subaitier*a Notebook No.s ",4r,y Sanitized. Does not contain TSCA GUI g f A L IHPORWATXM iCOHt.) Du Pont HL* m ~ n SponsorI Study Initiated - Cenalatadi In Life Phase Initiated - Completed; Ou Pont CShenleals I. I. du Pont de Honours and Coapany Vilaington, Delaware 12/7/92 - 2/2/93 12/8/92 - 12/11/92 - 4"ompany Sanitized,, Does not contain T$C PJ Du Pont HL* 28-93 Sktn Irritalo Tout with B-X9913 ln Babbite SUMMARY 8-19913 vu evaluated for acuto akin irritation potential in 6 Io m Io rabbita. The teat ubatanca produced alld or aodarata orythoaa and no or alight adaoa by 24 houra following application. By 48 houra alight to aodorato rytheaa and no to Mid odono varo obsorvod. By 72 houra the rabbita exhibited alight or Mid orythoaa and no or aiId odoaa. Undor tho condition, of thia atudy, 8-19913 wa~ a aodarata akin irritant. Work byi Hi Scott Karr Toxicology Technician Roviovod and Approved for Iaauoi < iA John V. larvar Study Director A / a /S 3 Acknovledgeaenta Tracy Pilliben and Bryan Croaaley alao participated in the conduct of thia atudy. JVS/alv 'OiBipany Sanitized. Does not contalo TSCA CBI Du Pont HUt 28-93 QUALITY ASSUMMO OOCWSHTATION (8-19913) Dti of Inoooi.'ion* Conduct - 12/8/92 Roeor4*t loport(o) - 1/26/93 Doto(o) Findlnoo 8 P o rfd to; Study Director - 1/26/93 HMWfdMnt - 2/1/93 Roportod Hbrl.f. Donna 8* Holt Quality Aaaorane Auditor -6 - Company Sanitized. Do; not contain TSCA CSi Du Pont HLR 28-93 m ssm m Tho purpose of this study vis to evaluate the skin irritation potential of H-19913 when applied to th# shaved, intact skin of New Zealand White rabbits. HIWIAW AND HBTB0P8 A. Anlwal Husbandry Young adult female Net Zealand White rabbits were received Iron Hare Marlend, Hewitt, New Jersey or Hasleton Research Products, Denver, Pennsylvania. The rabbits were housed singly in suspended, stainless steel, wire-mesh cages. |aeh rabbit was assigned a unique identification number which was recorded on a card affixed to the cage. The rabbits were offered approximately 123 grams of Purina Certified High Fiber Rabbit Chow* 15325 daily during the study and water was available ad libitum except as noted under Protocol. Rabbits were quarantined, weighed, and observed for\general health for approximately 2 weeks. Animal rooms were maintained on a timer-controlled, 12-hour llght/12-hour dark cycle. Environmental conditions of the rooms were targeted for a temperature of 20"C * 2*Cand relative humidity of 50% * 10*. Any excursions outside these Ganges were of small magnitude and/or brief duration and did not adversely affect the validity of the study. B. Protocol On the day prior to treatment, the hair of 6 female New Zealand White rabbits was closely shavef to expose the skin from the scapular to the lumbar region of the back* The body weights of the rabbits ranged from 2947 to 3320 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 waj:er. In the absence of visible evidence to the contrary, the test substance was assumed to be stable under the conditions of administration. Approximately 0.5 mL of H-19913 was applied directly to a 2-idch gauze square that was then placed on the test site. The patch 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. - 7 - ;ompan| Sanitized. Poes not comam i a C8S  Du font BLR 21-93 Approximately 24 hour# sfter application of the test substance the rubber sheeting vaa loeMNMf nd the kin at the corner of the feus squares vo narked with a waterproof pony wrappings and cause squares were then renewed. The Met sites were gently washed with Ivory* seep and warn water to renove qxeese test substance. Vhe skin was gently patted dry and the animals were returned to their cages. Approximately 24 48 and 72 hours after application of the test substance the test sites were evaluated for etythese edema and other evidence o f denial effects end were scored according to the Draise scale (Table I). The adjacent dress of the untreated skin were used for comparison. No other test! substances were tested on these rabbits. C. Records Retention All raw data and the fjinsl report will be stored in the archives of Haskell Laboratory for foslieeiegy and Industrial Medicine K. I. du Pont de Nemours Mid Company Ncjverk Delaware or in the Du Pont Records Management Center Vllnfn|(tn Delaware. H-19913 produced mild erythema with no edema in 5 rabbits and moderate erythema with slight edema In 1 rabbit by 24 hours following application. By 48 hours slight erythema with Ino edema was observed in 1 rabbit mild erythema with no or slight edema was observed in $ rabbits, and moderate erythema with slight or mild edema was observed in 2 rabbits. By 72 hours 2 rabbits exhibited slight erythema with no edema and 4 rabbits exhibited mild erythema with no or mild demje. Individual skin irritation scores are presented in Table II. A summery of skin responses is presented In the following table. Summary of Skin Responses to B-19913 Response No Rosponse Slight Mild Moderate Jsmheia 24 hr :TTSr " F 0/6 0/6 0/6 0/6 1/6 2/6 5/6 3/6 4/6 1/6 2/6 0/6 Rdems 24 hr .48 hr T F K r 5/6 3/6 1/6 2/6 0/6 1/6 0/6 0/6 5/6 0/6 1/6 0/6 Under the conditions of this study, H-19913 m s a moderate skin irritant. 8 ~ ^aniffeed. Does not comam t c a cm Du Pont HI* 20-93 im u . DRAIZ81 SCALE FjPR SCORING PRIMARY SKIN IRRITATION Evaluation of Skip Reactions Erythema and eachar formation No erythema Very alight erythema (barely perceptible) Veil-defined erythema Moderate to eevere erythepa Severe erythema (beet reddest) to alight eachar formation (injuries in depth) Value 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Edema formations No edema Very slight edema (barely perceptible) Slight edema (edges of arpa veil defined by definite raising) Moderate edema (raised approximately 1.0 mm) Severe edema (raised more then 1.0 am extending beyond the area of exposure) 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Abbreviations of other dermal effects ares A Abraded F pissuring I Intact N Necrosis T - Thickening 6 Pissuring vith C Eschar bleeding - No Effect S - fepideraal B Blanching Scaling L - Sloughing R - Rev Areas X - Compound Adhered to Skin SN Superficial Necrosis 1 Draiae, J. H., "Dermal Toxicity." Appraisal of the Safety of Chemicals in Poods, Drugs and Cosmetics. The Editorial Committee of the Association of Pood and brug Officials If the United States, Austin, Texas, 1959, pp. 46-59. - 10 sifjanf Sanitized. Does not contain TSCA CBI Du Pent BLR 28-93 M U SH IttPIVIPOAL SKIM IRRITATION SCORES SK1H BBgpnMM OBSERVED IN TEST RABBITS yOLLOyiBG TOPICAL EIPOSURE TO H-19913 Rabbit Nufcar 27558 27659 27662 27663 27664 27665 1Irylthcac 24 hr " S o r 7 hr 232 232 222 322 221 211 SdaM 24 hr 48 hr 72 hr 0 20 0 10 000 II2 000 000 - II - .CompanySanitizeduoesnotcumdifi idwAUti