Document npxvwqq58bzmRML5pRM8VjowX

: 3M MEDICAL DEPARTMENT TOXICOLOGY SERVICES To: Georjean Adams 290-4-01 cc: John Butenhoff 220-2E-02 From: Marv Case 220-2E-02 Subject: FC 95 and 143 Teratology Date: 26 May 1998 John passed on to me your request for someone to review and write an analysis on the eye lens defect that was reported in the the toxicology study files on FC 95 original and FC FC 143. 95 rat teratology study. I Attached are my review have reviewed comments and conclusions. You will note that the lens defect reported was subsequently shown to be a sectioning artifact and laboratories. To date, was not observed in latter teratology studies done at other teratogenic effects have not been shown with either compound at doses which are not maternally toxic Additional FC teratology studies are to be started soon. A FC 95 rabbit teratology study (we have no rabbit data), a rat FC 10 teratology study (we need to determine an NOEL level), and a rabbit FC 10 teratology study (we have no rabbit data) have been contracted and should start in June/July. 03114 Review of FC 95 & 143 Teratology Studies FC95 LAabroatraEtCor9ie5staenradttohleogsytsutduydryep(osrttudiys dnoa.te0d6D8e0cT.R01908008.) Dwoassecloenvdeulsct(eordala)t Rgiivkeenr to the porcecgunrarnetd raatttdhaemhsigwhedroese0,o1f, 150, amgn/dkg1.0 mEgv/kigd.encMeaotferfentaallttooxxiicciittyy(wraesduncoetdfwoeuingdhtatgaainny) dwiotshe olenveel.excNeoptisokne.letAalcahnadngsoeftintitshseueletnesorafttogheeniecyechwaansgefsouwnedreinfaolulnddosaet agnryoudposseinlcelvuedling trheepocrotnetdroolutbuatstdheeveinlcoipdmeennctealinehyieghabdnoosremaglriotuypawnadsthseigsniufmimcaanrtlyyofhitghheer.repTohrits scthaatensgethweas `compound was teratogric. Another rat FC 95 teratology study Laboratories and the study report is (study dated no. 154-160) was Nov. 1983. Dose done levels at Hazleton (oral) given to the pregnant dams were 0, 1, 5, teratology study). Maternal atonxdic1i0tymwga/skgfo(usnadmeatdtohseehliegvheelsr as in the previous two dose levels -- rat 5& 10 omfe/tkwgo.ofSitghnesohifghmadtoesmea(l10tomxgic/iktgy)wedarmes.redFuecteald twoexiigchittyg(aiinnc,raenaosreedxuitae,ritnhiennleossss,oafnpdupdseaatth t1o0ximcgit/ykgwaasndobrseedruvceeddaptutphewehiigghhetrs tatwo5 d&os1e0lmevge/lsk.g)Pwuhpicehxawmaisnarteiloanterdevteoatlheed mdaetlearyneadl oTshseifsictautdiyoncoatnctlhuedheidghthdaotsteheascowemlploausnvdisdciedranlotanaopmpaelairestoofcbleetfetraptaolgaetneiacnadt cdroysteorlcehvieslms. less than or equal to 5 mg/kg. An important finding was no eye of lens abnormality at any dose level Thacvaenjnuostt fcionndtraancyterdecfoorrdaorafabbritabFbiCt t9e5ratteorlaotgoylosgtyusdtyubdeyi;nsghdouolndehoanveFCda9t5a.by(Ntohteeenwdeof 1998) FC143 Arat FC 143 Laboratories atnedratthoelosgtyudsyturdeypo(rsttuidsydanot.ed0D6e8c1.TR19O811. 10) was Dose conducted at Riker levels (oral) given to the pgariengnaanndttrhartedeadmesatwhes)reoc0c,u0r.r0e5d, a1t.5t,he5,hiagnhdd1o5s0emogf/k1g5.0 mMga/tkegr.nalEvtiodxeincicteyo(frfeedtuacletdoxwieciigthyt wpaupssn(ortelfaotuenddtoatmaantyemdaolsetolxeivecli.ty)A,lntohosukeglhetdaellaayneddsoosfstitfiiscsauteiotnewraatsogfeonuincdchinantgheeshiwgehredose fleonusnodftaht eaneyydeowsaeslefveolu.ndAisn walalsdotshee cgarsoeupisn FinCcl9u5dirnagt ttheeractoonltorgoylsbtuutdyt,heaicnhcaindgenecienitnhheigh dose group was significantly higher. However, in this study report this finding is 03115 attributed to an artifact created by sectioningof the eye. The study conclusion is that the compound was not teratogenic. MAendiocutaslidCeolcloengseu,ltviasnitteadn3d Mteraantdolroegvyieexwpeedrtt,heDrratE.puMapresyhealslpeJcoihmnesnosn ifnrqoumesJetfifoenrfsornom the StewcotiRoinkienrg raarttitfearctastoalnodgynosttucdioems.poHuendcorneclautrerdedtetrhaattoltohegyeayben/olremnaslcithiaensg.es were,infact, pLAarberoagbrnbaaitntotrFriCaebsb1ia4tn3ddtatemhresatswoteluordgeyy0rs,etpu1o.dr5yt,(i5ss,tdauadntydendSoOF.em0bg.6/8k11g9.T82B.0M3aD9toe8rs)neawllaestvoecxlisocn(idotruyacl(t)reegddiuavcteenRditkwoeetrihgeht `aegtvsteirnli)bbouucttecduhritrgoehedmdbaotrsyetohtpeouxhpiiscgihhtadyd.osselNiooghftsl5kye0liemntgca/rlkegaa.sneddTsironfucteitdfieestnsaculeetotofexriraciitbtoyvgaewrniaiascticnohonatsnfwgoheuisncwdhearwteaasnfyoudnodse at any dose level. The study conclusion i that the compound was Rot teratogenic. tSetraaptloelsoagnydstcuod-iweosroknerFsCat14D3u.PoInntonHaesskteuldly,Lapbroergantaonrtiersathdavaemsdowneereadddoistieodnaolrarlalty at 0 and 100 mg/kg (report inhalation doses of dated 0, 0,1, Jan. 1.0, 1982). 10 and In 25 other study, pregnant rat mg/m' (report dated Jan, dams were exposed to 1982). These repeat fpSoturubidlciiiestshyedadindadnnotdtetrrhaeetvoregeaeflneiarcneynpcoeetyeines:tioSaftllaoepfnlsaesmabRmnEoo,rnmiBauluirmtgiepesessrfiBnlAuro,artoKpoeucrptsma.snoWTaDhtie:s(TwAhoPerFkOem)hibaynsrtobh-efeeenrtaatl Fund Appl Toxicolo 4:429-440, 1984. Conclusion Ttehruast,ogtehneiwceeifgfhetctosftinhaeniemvaildsenwcheeinnddiocsateedsatthaltevneelistwhehricFhCa9r5e nnootrmFaCte1m4a3llcyautsoxeisc. Even `2atmasmteaectrteniraolnnaitlnolgxyiacrtitotiyxf.iacctTdhoasenedsle,wnasefscfehncaottnsgfseoeueonnbdsienurptvhoeendpriunepprseaatwtpesurtpeusdtiihenossRaeitkgieenrndeLreaapbleolnrydaeatnsotsroilceaisbaotsretadutdowiriieestshw.as MPMararvairnseT. sCa,s:e, D[VMC, PrAD 3CoMrpToorxaitceoSlcoigeyntSiesrtvices hytreDeate 0311