Document b5aQZNxO3bdo49yeN0D9EwLM0

ARaRE _ 3255 isd `TRADE SECRET ARaR6_ 3258 Duront11269 Study Tide H-25357: Oral Approximate Lethal Dose (ALD) in Rats Laboratory Project ID: DuPont-11269 AUTHOR: Carol Finlay, B.A. STUDY COMPLETED ON: August 9, 2002 PERFORMING LABORATORY: E.L du Pont de Nemours and Company Haskell Laboratory for Health and Environmental Sciences Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 `Company `Sanitized.Dows not containoeTSCACEE yy ei e rep------Temee-------------- Fae TorS H-25357: Oral ApproximateLethalDose (ALD) in Rats DuPont-11269 --_ CERTIFICATION `We, the undersigned, declare that this report provides an accurate evaluationofthe data obtained from this study. Reviews by: Ja Peer = Tamed. Mackay I `Associate Scientist -fy Sz = LasuedbyStudyDirector: iiFiiay. B.A SuffToxiologis. 9.Quy -0r Company Senitzet notcontain TSCAcal --_ IT 525357: Ort Approsmate Lt Doss (ALD) n Rats. --_ STUDY INFORMATION subessciN anN ce\ `Synonyms/Codes; jo H-25357 Submiter's Noebook Number(s: [ENN Haskell Number: 25357 as Regs omeJUNI | ue[RI Dron 11269 Phusical Characteristics; Amber quid Sponsor: EL du Pont de Nemours and Company Wilmington, Delaware 19898 US.A. StudyIntistedCompleted: Jone 14, 2002. (see reportcover page) In-Life Initiated/Completed: July 3, 2002/July 22, 2002 Company ms somrmeT 125357: Oral ApproximateLethalDose (ALD)in Rats Dupont 11269 -- STUDY PERSONNEL Study Director: Carol Finlay, B.A. Management: Scott E. Loveless, Ph.D. Primary Technician: Diana L. Ritchie Toxicology Report Preparation: Sean M. Callaghan, B.A. Management: Nancy S. Selzer, M.S. Laboratory Veterinarian: William Singleton, D.V.M., ACLAM. my Sanitized.Doesnotconta nTSCACE! ER F-25357: Oral Approximate Lethal Dose (ALDi)n Rats Duponi 11269 --~ SUMMARY H-25357 was administered as a single oral dose by intragastric intubation to male rats at doses of 670,2300, 3400, 5000, 7500, and 11,000 mg/kg. Following dosing, the rats were weighed and cbserved for mortality and clinical signsoftoxicity over a 14-day observation period. No deaths occurred. No clinical signs were observed,andno biologically important body weight loss occurred during the study. Under the conditionsofthis study, the oral ALD for H-25357 was greater than 11,000 mg/kg of body weight. This substance is considered to be very low in toxicity (ALD greater than 5000 mg/kg) when administered as a single oral dose to male rats --~ Company' ized. Does 0 ain TSCACS! --_ I H-2557: Oral Approximate Lethal Dose (ALD)in Rats DuPont 11269 --_ INTRODUCTION `The purposeofthis test was to determine an approximate lethal dose (ALD) of H-25357 when administered as a single oral dose to male rats. The ALD was defined as the lowest dose administered which caused death either on the day of dosing or within 14 days post exposure. MATERIALS AND METHODS A. Test Substance `The test substance, H-25357, was supplied by the sponsor as an amber liquid. The test substance appeared to be stable under the conditionsofthe study. No evidenceofinstability, such as a changeincoloror physical state, was observed. B. Animal Husbandry Male Crl:CD(SD)IGS BR rats were received from Charles River Laboratories, Inc., Raleigh, North Carolina. Rats were housed singly in stainless steel, wire-mesh cages suspended above cage boards. Each rat was assigned a unique identification number which was recorded on a card --~ affixed to the cage. The rats were tail-marked, using a water-insoluble marker, with the last 3 digitsofthe animal number. PMI Nutrition International, LLC Certified Rodent LabDietTM 5002 `and water were available ad libitum. As specified in the Haskell Laboratory animal health and environmental monitoring program, the following procedures are performed periodically to ensure that contaminant levels are below those that would be expected to impact the scientific integrity ofthe study: + Water samples are analyzed for total bacterial counts, and the presenceofcoliforms, lead, `and other contaminants. + Feed samples are analyzed for total bacterial, spore, and fungal counts. + Samples from freshly washed cages and cage racks are analyzed to ensure adequate sanitation. by the cagewashers. Certified animal feed is used, guaranteed by the manufacturer to meet specified nutritional requirements and not to exceed stated maximum concentrationsof key contaminants, including specifiedheavy metals, aflatoxin, chlorinated hydrocarbons, and organophosphates. The presence ofthese contaminants below the maximum concentration stated by the manufacturer would not be expected to impact the integrityofthe study. -- Company Sanitized. Does not conta'n TSCA CBI -- --- H-25357: Oral Approximate Lethal Dose (ALD) in Rats DuPont 11269 --_ `lTahbeoraantiomraylahneiamlatlhvaentdereinnavriiraon.nmeEnvtaalluamtoinointoofrtihnegsperdoagtraadmiidsnaodtmiinnidisctaetreeadnbyyctohnediattitoennsditnhgat affected the validityofthe study. Rraotosmswewreerweemiagihnetdaianneddoobnsaertviemderf-ocrongternoelrlaeld,he1a2l-thhoduurrliingghtth/e126--hdoauyr qduaarrkacnytcilnee. peErnivoidr.onAmneinmtaall c5o0ndit1i0o%n.sofEtxhcuersriooonmssowuesriedetatrhgeesteedrafnogreastweemrpeeorfatsumraeollfm2a3gni1tuCdeaanndd/reolrbartiiveefhduumriadtiitoyn oafnd did not adversely affect the validityofthe study. Cc. Protocol `vTohleutmeestssaudbmsitnainscteerweadswaedrmeinciasltceurleatdendebaatstoed |ornattpheertdesotsseubrsatteanbcye idnetnrsaigtasytorifc 1i0n9t0ubmatgi/onm.LTahned b1o1d,0y0w0emigg/hksgocoflbloecdtyedwoenigthhte dinayioncfrdeomseinntgs.ofDaopspersoxaidmmaitniesltye5re0d%.ranAgdedditfiornoamll2y3,001 rtaot was dFooslelodwaitn6g7a0dmmign/iksgt.ratTihoenodfotshiengtedsatyswubasstatnecste,daryatsI;weporseteoxbpsoesruvreed dfaoryc1l4inwicaasl stiesgtnsdoafyto1x5.icity. "peTrhieodr.atsOwbesreervwaetiigohnesdfoarndmoorbtsaleirtvyedanadt lseiagsntso3ftililmneessas,wienejkurty,hrooruagbhnooutrmtahleb1e4h-advaiyorobwseerrveatmiaodne daily throughout the study. Pathology examinations of test animals were not performed. `CompanySaniized.Doesnotcontain TSCAGBI --~ - 125357: Oral Approximate Lethal Dase (ALD) in Rats ~~ RESULTS AND DISCUSSION DuPont 11269 A. Dosing and Mortality Data No deaths occurred during the study.Thedose regimen and the mortality resulting over the 15day test period are detailed below. g/kg) (mL) [eo[ots [2300 [oss [30[000 [sooo| 12 [soo[is Loew""28 mg/mL) | Weight (5) | Mortali 1 woo [ ms2| no | | two [miss| no | 1 iwo [278 | no | | iso | 2669 | No | | iow | 2667 | mo | T woo[a1 | wo | B. Clinical Signs and Body Weights No clinical signs were observed, and no biologically important body weight loss occurred during the study. CONCLUSIONS Under the conditions of this studs,theoral ALD for H-25357 was greater than 11,000 mg/kg of body weight. This substance is considered to be very lowin toxicity (ALD greater than 5000 mg/kg) when administered as a single oral dose to male rats. RECORDS AND SAMPLE STORAGE Specimens(ifapplicable), raw data, and the final report will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware. CompanySanitized. DoesnotcontainTSCACBI mm