Document gjrVLnjQk09J3pyrn3b69Y89

ems ttn pvr nin 00 FIRA9e 030M Studies and Other Information on Certain Perfluorooctane Sulfonate-Related Compounds [iwoasrosen|eippeorossass somemitostpt ene Acute Toxicity 1) Acute Oral Toxicity Screen with T-3493 in Albino Rats, Safety Evaluation Laboratory, Riker Laboratories, Inc., Project No. 0884AR0010, 3M Reference No. T3943, February 7, 1984 2) Primary Skin Irritation Test with T-3493 in Albino Rabbits, Safety Evaluation Laboratory, Riker Laboratories, Inc., Project No. 0884EB0009, 3M Reference No. T3943, February 7, 1984 3) Acute Ocular Irritation Test with T-3493 in Albino Rabbits, Safety Evaluation Laboratory, Riker Laboratories, Inc., Project No. 0884EB0008, 3M Reference No. T3943, January 24, 1984 Immunotoxicity 1) Guinea Pig Maximization -- Method, Summary, and Raw Data Appendix, Hazleton Laboratories America, Inc, Project No. 40703984, 3M Reference No. T-3609, October 5, 1984 (plus May 13, 1985 report amendment) Genotoxicity 1) Chromosomal Aberration Study of Sample D-1 in Cultured Mammalian Cells, Mitsubishi Chemical Safety Institute, L1d., Study No. 2L162, 3M Reference No. T6322.3 (FX-13), October 23, 1995 2) Mutagenicity Testing of2-{N-cthyl-N-perfluoroalkyl (C=1~8)sulfonylaminoJethyl acrylate in Bacterial Reverse Mutation Assays, BML, Inc., Study No. 2862, 3M Reference No. T-6322.5 (FX-13), April 24, 1996 3) In Vitro Microbiological Mutagenicity Assays of 3M Company's Compound T-3609, SRI Intemational, Project No. LSC-3145, September, 1984 Repeated-Dose Toxicity 1) Twenty-Eight-Day Repeated Dose Oral Toxicity Study of Sample D-1 in Rats, BioMedical Research Laboratories Co, Ltd, Study No. BMR143C, 3M Reference No. T6322 (FX-13), February 16, 1993 -9Q- 005188 Experiment No.: Conducted At: Dates Conducted: Conducted By: Reviewed By: Acute oral Toxicity soreen with T3493 in Albino mats 0884AR0010 GEOTEIEVERRN, FEB 101984 su J PrXi oS . RsiakfeertyLaBbroarlautaotriioens,LabToocr:atory St. paul, Minnesota Decesber 30, 1983 to January 13, 1984 DBWi.nea.tivoen,miokt,ar8d afBeatre TSotxaiycodliorseicattor ARaPnmTi>eyO, gg SAeonuitoerToTovxiiccootloonsyint 2ylstdate dc: XMeZ7.. chaesens Wob. GMreicfofrimtihek . 005189 - 1. Summary The acute oral toxicity screen with T-3493 vas conducted from December 30, 1983 to January 13, 1984 at Riker Laboratories, Inc., St. Paul, Minnesota using male and female albino rats ranging in body weight from 227-272 grams. The test article was administered by gastric : intubation at a dosage level of 5,000 mg/kg body weight with no mortalities noted during the 14 day observation period. Diarrhea was noted in two males on day one and had subsided by day three and alopecia was noted in one female on days five through nine, inclusive. Body weight gains were noted in all animals at the end of the study. Necropsies performed at termination of the study revealed no visible lesions. The approximate oral DSO of 7-3493 is greater than 5,000 ng/kg in fasted male and female albino rats. Introduction The objective of this stuly was to determine the acute oral LDSO of 7-3493 in albino rats. This study is not regulated by the Food and Drug Administration's Good Laboratory Practice Regulation of 1978, although the standard operating procedures of this laboratory adhere to the general principles of this regulation. The raw data generated by the Study Director and the final report are stored in the conducting laboratory's archives. 005190 2. Method and Results Young albino rats were used in this test. All animals were held under quarantine for several days prior to testing vith only anisals which appeared to be in good health and suitable as test anizals at the initiation of the study used. The rats were housed in suspended, wire-mesh cages in : temperature and humidity controlled rocms and permitted a standard laboratory ate? plus vater ad 1ibitum except during a 16-20 hour period immediately prior to gastric intubation vhen food vas withheld. The rats were administered the test material at a single dosage level. ALL doses were administered directly into the stomachs of the rats using a hypodernic syringe equipped with a ball-tipped intubating needle. After gastric adainistration of the test article, the rats were returned to their cages and observed for the following 14 days. Initial, seven day ana final body weights, mortalities (Table 1) and adverse reactions (Table 2) were recorded. A necropsy vas conducted on all animals that died during the study as well as those euthanatized at the end of the 14 day observation period (Table 1). The protocol, principal personnel involved in the study, composition characteristics and Quality Assurance statement are contained in Appendices I - Iv. 2RCahlasrctoens pPuirvienraBLraebooariantgorLyaboCrhoawt,oriReasl,stoTnneP.uriwnial,ainSgt.tonL,ouiKsA, HO < Popper and Sons, Inc., New Ryde Park, NY 005191 " 3. S Dose? Animal (mg/kg) Sex Number TABLE 1 ACUTE ORAL TOXICITY SCREEN - ALBINO RATS vith -3493 Mortality, Necropsy, and Body Weight Data Tnaividual Body Weights (3) 0 Test Day 7 Number1: NuNmubmebrerTeDsetaedd 5,000 3R7799770 224566 238092 330222 o/s 37972 37973 254 272 299 312 323 350 3R7974 240 262 279 5,000 F338R78997 225388 225623 227686 os 387898 3R7899 227 243 245 267 257 282 37900 251 288 303 PeDrecaednt o --_-- 2 he test article vas administered as a suspension in cottonseed oil. The acute oral LDSO is greater than 5,000 mg/kg in fasted male and female rats. NNeeccrrooppssiyes performed upon termination of the stuly revealed no visible lesions. 005192 ote 2 ACUTE ORAL TOXICITY. SCREEN - ALBTIO RATS with 24) Suemary of Reactions e-- con ---- e-- e `hssvae tion Fericas-- ee ieeeee e Resctions mer Mnsbor Mffectet/Mupherbolnewd pose sex 10 ew Tz 3 4 5s 6 7 8 9 doom oun ou 3,000 Dtas"then us vs ors 5.000 Nope.cta [RVR RV RVR i 828a 1 ats . Riker Experiment No. 2220 APPENDIX I 5. PROTOCOL rest. Acute Oral Toxieity SPONSOR: aM__Conzereial Chenisils --_-- CONDUCTED BY: SafetyEvaluation Laboratory, Riker Laboratories, inc., St. Paul, Minnesota TESTARTICLE: T-3493 controLmmmoe: More. 0 PROPOSED STARTINGIOMPLETION DAOFTTeEsT: (2/3 = 3/74 - Testsvstem: AcgINO FAT , CD SouRcE: Crnmise RVER | RupaneTon, Mes. SNWeeuxim:gbhetr#:,RaFn5g,e5: 200-300 rans OBJECTIVE: The objecotfithvies test wil be to characterize theacute__T_al____ toxicityoftho test aGrutciiclbeiitny aolfbriensopo_T n_se_,a histt oricals us,. ese in ha#nd3itnsgandgewneerraelsealveacltaeidlay.s a test system for repro- METHOD: The animals wil be housed in staniss steal suspended wire mesh cages In temperature and huidly cEooadnctuhrrolealnewidhmiraclohowmwiislldbcuarioindgnebnotatihosdtthobepyhqeuocaaonrlniaonmrtadcilondeniunagmn,bdeatrcessctoorpndeiranciogadrsod,awftifhteihxlefadobooodrt2ahtaoernyud'tswsastdteearnotdoafhrfdeereocdpearadatiAgibnisgetiunpmgr.lo.e- . draodiesqacugaetateolfsyuSpcph0alre0amce0tnetrmaiglz/edkohgseawigolel xblaeivealdsom.fiAtnhniesytteaedrsdetidtrieioacnacelh,daaoncsidamiagloe,nalhelovewalensvmewriil,sbifewitdhliosbcoduomasedanmgitneeidslteavenerldedfdlotehedswtnieotstht {acbilhsoprnwohtfitoocchohl.tehTehfeoalntoiowsmianlgast1wt4iledabwyaisl.rbIenoitaiiaclrmainn1dsftitanhralerdbco0actgyhewseeaiagnnhidtmsaolbwssialirlnbvteehdareffcooorrrmdaenrdya.cAuenlivgoerdwoasfrsrdonmebcetrhhaoevpissopyrowanlhsioferc,h will include, but not be limited to; heart, lungs, liver, kidneys and general gastrointestinal tract will be c{Coofrntcdpoudcrtiweoidt.hoAnsnpayollcgiarinocismsmaelansbtnwoohrnimca1hlidtiiheeesdowurhrgiiacnngh taahonedcoorbnsdseuircevteoodfbtdsuehrreivnetgde.stthAealscorwnaedlwlucdatastoatfhgteehneaannrieamclarelodspssbuyyrwvtiihvleinbsgatutrdhoye- iractr and the final ropor will be sored n he Riker Laboraloris' Archive, St. Pau, Minnesola. 2 LD Purina foor LawboiraetorByEChowwi,tRhalusgtzonoPurFinoa,rSt.ALouWis7,2M0issoHuroiur Arion : Pravr To 05056, pi_--e Sp2on0s,orEl Corn . Zohfirsy" ~ SD ioa Dnector vandal =- 2f:Thjiiss 005194 : 6. AppENDIX IT Principal participating Personnel Involved in the Study Name D. M. Markoe, Jr., BS K. L. Eobens, BS X. D. O'Malley, BS G. Cc. pecore Function Tsotxuidcyoploigriescttor . STuopxeircvoilsoogry Testing sceuntieorToTxoixciocloolgoygist sAunpiesralvisLoarboratory 005195 - 7. Avex 111 Composition Characteristics his study is not regulated by the Good Laboratory Practice Act of 1978 and therefore information pertaining to composition characteristics ia not applicable for inclusion in this study. 00519 - 8. appmDI Tv Quality AssuranceStatement This study is not officially regulated by the Good Laboratory Practice Regulation of 1978, and therefore a statement signed and prepared by the Compliance Audit department is not applicable. he standard operating procedures of this laboratory does adhere to the general principles of this regulation. The Compliance Aulit drsartment does inspect different significant phases for stulies wdervay in the Acute Soxicology Laboratory on a recurring cycle, and the facilities are examined on u three month schedule. In addition a select number of Research & Development studies are xoutinely picked at random from the Archives by the Compliance Audit department for review. 005197