Document rxL1007eKgw9Bzw2G2RxNkOqE

AR 226 _ 0665 PFOA Acute Toxicity - / 000814 @HaH R E zieE sTR yons FINAL REPORT 5Karen Armstrong TBouxrilcionlgogy320S-esrtv.i0c8es St. Paul, MN 55144-1000 Sample: T-4416 HLA Number: 91201739 7 oT EQ 2. = APR & 220 zu J Kn = Enclosed: Acute Oral Toxicity Study in Rats (OECD Guidelines) Key Personnel 3o L Pethos tosy Report Methodology o Summary of Results o Individual Pathology Comments 0 Raw Data/Appendix Signed: StS udy Doirh decitsn Wu. Rents Torscatosy mSo grnu, ne 2a-9e0 rE oo OLer @ HHE E AAZZLa T LEETTOn ONN HLA Number: 91201739 Sample: T-4416 AcuteToxicology Steven M. Glaza SSteuldyonDirSeecpteorrvisar Steven R. Sorenson Study Coordinator Patricia Padgham Group Leader SRehpaorretn CL.oorHgoiwnesrtyor QualityAssurance Deborah L. Keller Manager Page 2 KEY PERSONNEL LaboAnrimaalVetteroinrariyan Cindy J. Cary, DVM Diplomate, ACLAM AnatomicalPathology Thomas E. Palmer, PhD Anatomical Pathologist Dennis Hoffman Group Leader fAnnreaMtosher Group Leader Pathology Data oLor --- mr seme 000516 @ HT E AZLE n ETOT N HLA Number: 91201739 Page 3 Sample: T-4416 eTooL06Y Test materia: Taio Objiesctaidvmei:nistTeoreadssebsysortahle Physical Description: Purity and Stability: Storage and Retention: Safety Precautions: gaacvuatgee ortaol rattosx.i'city produced when a test material Clear colorless liquid Sponsor assumes responsibility for purity and csotnadbiitliiotnys)d.eterminations (including under test Th test Baiertal was stored at roon temperature. Any unused material will be returned to the Sponsor Searing to HA Standard operahts Procedure: Normal handling procedures were used according to HLA Standard Operating Procedure. Test Animal: Adult albino rats, Crl:CDBR, were procured, separated by sex, maintained in group cages in temperature- and humidity-controlled quarters, provided continuous access to Rodent Chow 5001, Purina Mills, Inc., and water, and held for an acclimation period of at least 7 days. Animal husbandry and housing at HLA comply with standards outlined in the "Guide for the Care and Use of Laboratory Animals.? If variations from the prescribed environmental conditions existed, they were documented and considered to have no effect on the study outcome. No contaminants were expected to have been present in the feed or water which would have interfered with or affected the results of the study. Acclimated animals were chosen at random for the study. Five male and five female rats, weighing from 204 to 299 g, were used for each dose level. The study consisted of three dose levels (0.2, 1.0 and 5.0 g/kg of body weight). Test animals were housed by sex in groups of five and identified by animal number and corresponding ear tag. Food and water were available ad 1ibitum throughout the study, except for an overnight period just before test material administration when food, but not water, was withheld. Reason for Species Selection: Historically, rats have been used as a representative of a rodent species and are preferred by various regulatory agencies. Sonn steres by sage. Preparation and Administration of Test Material: The test material was administered as received. An individual dose of the undiluted material was calculated for each animal based upon its fasted body weight and The dose volume of the test material varied for each dose level basedupon the bulk density of the material of 1.28 g/mL. pbRaEesEesr oom mie 000817 @ HE T azLy E ETO, a N HLA Number: 91201739 Sample: T-4416 Page 4 Reason for Route of Administration: Historically, the oral route has been the route of choice for administering a known amount of test material. Observations: The animals were observed for clinical signs and mortality at 1, 2.5 and 4 hours after test material administration. The animals were observed daily thereafter for 14 days for clinical signs and twice daily for mortality. Animals were weighed just before test material administration. Surviving pahnaismealsorweartedewaetihghe(dwheangaisunrvaitvaDlayex7ceaenddedat 1 tdearym)i.nation of the experimental Pathology: All animals whether dying on test or euthanatized at termination of the experimental phase were subjected to a gross necropsy examination and all abnormalities were recorded. After necropsy, the animals were discarded and no tissues were saved. StwaatsistciaclaclulMaettehdodbsa:sedThueponLD.thevaolbuseerfvoerd mmaolretsa,lifteymaulseisnganad gtohmepuctoemrbipnreodgrsaemxes utilizing a modified Behrens-Reed-Muench Cumulant Method.' No other statistical amalysis was performed. Location of Raw Data and Final Report: The raw data and a copy of the final report will be retained in the archives of HLA. L So n somo 000818 @ HHS SaAEzE ZiEeE RtooNS n. SHaLmAplNeu:mberT:-441961201739 Page 5 Test Anan: Albino Rats - crl:ComR SUMMARY OF RESULTS Source: Charles River Laboratories, Inc., Portage MI Date Animals Received: 12/04/89, 12/18/89 and 01/08/90 Method of Administration: Oral Gavage Start Date (In-1ife): 12/28/89 End Date (In-1ife): Female- 0.6 gk of Body Hetaht Estimated Oral LDg:, Male - 1.8 g/kg of Body Weight 95% Confidence Limits - 0.7 to 4.9 g/kg 95% Confidence Limits - 0.2 to 1.5 g/kg Sexes Combined - 1.0 g/kg of Body Weight 95% Confidence Limits - 0.4 to 2.4 g/kg 02/16/90 Sex Male Female Dose Level --laska) 0.2 1.0 5.0 0.2 1.0 5.0 Average Body Weights (q] Initial Day7 Terminal 290 332 272 264 274 ---- 362 315 --- 211 247 254 233 257 268 230 --- n-- Mortality (Number Dead/NumberDosed) 0/5 1/5 5/5 0/5 4/5 5/5 HnEeATmEaR J 000819 @ HHEaARzE ZLOLeEETa ToOn&N HLA Number: 91201739 Page 6 Sample: T-4416 Observation Appeared normal Clinical Signs (Number of Animals Affected) TN -------- 10 2540123456789 101 1213 1& Males(0.2 g/kg) 5 5 5 555555555 5 5 5 5 5 Appeared normal females(0.2o/ka) 5 5 5 555555555 5 5 5 5 Males(1.0 a/ka) Appeared normal 5 5 5 521112333 3 3 3 4 4 Hypoactivity 0 0 0 0322221110 0 0 0 0 Red-stained face 0 0 0 01222111111 00 0 Yellow-stained urogenital area 0 0 0 013331111 1 11 0 0 Ataxia 0 0 0 000001111 0 0 0 0 0 Thin appearance 0 0 0 000001111 1 0 0 0 0 Diarrhea 0 0 0 000000011 0 0 0 0 0 Death 0 0 0 010000000 0 0 0 0 0 Eem(a1.l 0 ae/ks g) Appeared normal 5 5 5 511111111 1 1 1 1 1 Hypoactivity 0 0 0 022100000 0 0 0 0 0 Red-stained face 0 0 0 022100000 0 0 0 0 0 Ataxia Prostration 0 0 0 001000000 0 0 0 0 0 I 0 0 000100000 0 0 0 0 0 Death 0 0 012100000 0 0 0 0 0 n W Emp E, wee soompi 000820 @ HazLeTon SEER HLA Number: 91201739 Sample: T-4416 Pag7e FCulmibneicralofSaigrnesa'(sCoAnFtTienuceede)d) Observation --_ --A -- ---- 1025401 234567683910 015 U1 Males(5.0o/ka) Madimet Appeared normal HyDpiaorarchteiavity Red-stained face Death S0 oSfodabgiIIIIiiiioloiool 1 0 0 0 - - + + 4... 40 44 44 11 .- .4...o.oo- a.oD 110 0 2 4 1 - - - - eee... 0 0 1 4... .-- -L - L. L * - One animal found dead after the morning observation. KMoermsber Appearednormal Diarrhea Hypoactivity Red-stained face Death Eemales(5.0o/ka) AEEEEEEEEEEEE S0E 1 E b33 3b 2 o0e- c- ie + i4 isIeiei siia oe in eooeoa 0 1 FE 0 2 1 2 - + + + a. - LLL. f --A 000521 @paSHzEaeEzeetonn, HLA Number: 91201739 Sample: T-4416 INDIVIDUAL PATHOLOGY COMMENTS Animal Number 50366 50367 50363 50369 50370 50501 50502 50503 50504 50500 Sex M M M M M F F F F F Dose Level: 0.2 g/kg of Body Weight _T_estDay Died Sacrificed - 14 - 14 - 14 - 14 - 14 - 14 - 14 - 14 - 14 - 14 Necropsy Observation No visible lesions No visible lesions No visible lesions No visible lesions No visible lesions No visible lesions No visible lesions No visible lesions No visible lesions No visible lesions oo Page 8 ER J 000822 @HE EazELeEn ToN RE ---- HLA Number: 91201739 Page 9 INDIVIDUAL PATHOLOGY COMMENTS (continued) Dose Level: 1.0 g/kg of Body Weight Animal _T_estbay Number Sex Died Sacrificed NecropsyObservation 49861 L - 14 No visible lesions C49862 M - 14 No visible Tesions 49863 M - It) No visible lesions 49864 M 2 - Stomach, Glandular Mucosa: diffusely red 49860 M - 14 No visible lesions C4992] F 3 - Stomach, Glandular Mucosa: diffusely red ca9917 F 2 - No visible lesions ca9918 F 4 - Perinasal Discharge: red Stomach, Glandular Mucosa: multiple dark areas, up to2x 4mm C49919 F 3 - Stomach, Glandular Mucosa: diffusely red 49920 F - 14 No visible lesions g EpEsp Em e823 @HaE [ HzAE LZn eLETEoTe NON HLA Number: 91201739 Sample: T-4416 Page 10 JHOIVIOUAL PATHOLOGY COMRENTS (continued) Dose Level: 5.0 g/kg of Body Weight Animal Number Sex Died TestSaDcaryif_iced NecropsyObservati. on 49191 M 1 - No visible lesions 49192 M 1 - No visible lesions 49193 M 1 + Stomach, Glandular Mucosa; multiple brown areas, up to 3x 1mm 49194 M 0 - Stomach, Glandular Mucosa: diffusely dark red 49490 M 1 - No visible lesions 49131 F 0 - Stomach contents: clear white fluid om 49132 F : - Stomach, Glandular Mucosa: multiple brown areas, up to c49128 F 0 - Stomach Contents: clear white fluid c4s129 F 0 - Stomach Contents: clear white fluid 49130 F 1 - No visible lesions EB--_sE--nE--, ne comet eam, 000824 @HaHR EzRAiRZLE ELeEEtEToT OnN Sample: T4416 HLA Number: 91201739 Page 11 REFERENCES 1. "Acute Oral Toxicity," Organisation for Economic Cooperation and Development's Guidelines for Testing of Chemicals, Section 401 (adopted May 12, 1981). 2. NIH Publication No. 86-23 (revised 1985). 3. Tahnadkuirt,s CA.onKf.ideanncdeFeLziimoi,tsW.UsiLn.,g a"AMoCdoimfpiuetderBePhrroegnrsam-Refeord-HEusetnicmhatiCnugnulLDa,nt Method," Drug and Chemical Toxicology, 4(3):297-305 (1981). HnfEraeRstE, eo etme meron 0082S @HHPL AAZEZLELr EEETOONn N& HLA Number: 91201739 Sample: T-4416 Page 12 PATHOLOGY REPORT Tahnedre5.0werge/kg1)0 nraetcsrop(s5iemda.les,The5 afneimmaalelss) thfartomdieeadchonoft3estdos(eDOTl)evweelrse (0.2, 1.0, refrigerated and necropsied within 24 hours, usually the same day. All surviving animals were euthanatized and necropsied at the termination of the study. The dose level, day of death, and gross observations recorded for each animal are on page 8 through 100of this report. A11 animals in the 5.0 g/kg dose group died on test. At necropsy, the only changes observed were in the animals that died on test. The most frequently recorded observations pertained to the content and coloration changes in the wmiutchosainogfesttah,e psotsomtamcohr.temThcehsanegef,inodringbsothp.ossAilbllyrermeapirneisnegntobtseestrvamtatieornisalinmitxheed DOTs were considered postmortem change, incidental, and unrelated to the test material. There were no visible lesions in the sacrificed animals. me Thomas E. Palmer, PhD Pathologist (91201739.cjr) __-3-%0 Date eEErEn J---- 000826 | Ln wa: 9201939 PERSOANCIUETLE STIOGXUIACTOULROEGYSHEET [A Becky Beckwith JobTitle Sionsture Initials Lab Animal Technician hoy Loki AA Ann Bursaw Sr. Clerk LorBrencarr Gni- Anthony Cass Cindy J. Cary, DVM Kari Gassen Steven H. Glaza Ben Haley Lab Animal Assistant CielemosyLona, ac Lab Animal Veterinarian Pn Ge Sr. Lab Animal Assistant i Section Supervisor wo Sr. Lab Animal Assistant RH Jeff Hicks Lab Animal Technica ian es nd 7 Sharen L. Howery Research Assistant 4 sO Jin Jirschele Lab Animal Assistant ke faditer / Wayne Madison Senior Section Supervisor {(h@ Jy7hncisein jn Bud McDonald Sr. Lab Animal Assistant Bud/BApald Bred Eileen comet] Adninistrative Clerk E5eud Cond? Lonzr. Henry Mikula Lb imal sistant Ze Z 2 4] Albert Oleson sr. Lab Animal Assistant CUAObarr, AOD : Patricia Padghan Group Leader fwzi 2cllon. 732 Jane Polnow Lab Aninal Technician Steven R. Sorenson Study Coordinator Dawn Thieding Clerk Op SRS 27 Amette R. Turner Sr. Clerk Clase mp Bo Romess . Solon Damon Air Sz AB (05/11/89) 000827  BEST COPY AVAILABLE ) a meaams Study Titles feuteOralonlity - vnTLE a1 To weriats_T-4 416 a ot vaicisi_NJA Teen i ts et560 | esa pele ITEEY -- iE ima s tna to (GE ote Low2 li_ahQa) Fasked btw/Tina/iacatclon 24 90) Fro%pnt su8 500 LIN noonte. JO tnt 20 st 0 wen coioselnilontpli. 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