Document Znwme9pv6epvVVyKVkZqjgp4p

26-Week CapsuleToxicitSytudywithPerfluorooctanesulfoAncicdPotassiumSalt (PFOS) inCN-nomolausNlonkeys CurrentSummary asof,Nfav4,2000 T'hepurposeof thistudywas toidentiftyheearliecsltinicalmleyasurablebiologicraelsponsefrom repeateddailyexposure topotassiumperflucrooctanesulfonate(PFOS) and to correlatethisresponse to set= conc@-nrtabonfsorpurposesof riskassessmentard medicalmonitoringof exposedpopulations. Groups of male and femaleCvnomolgus monkeys receiveddailydoses of 0 (sLTp,er sex),0.03 (fourper sex),0.15 (sixper sex),or0.75 (sixper sex)mg/kg,'daypotassiumperfluaroocta-nseulforiatfeor26 weeks by capsulevia gastr-iicntubationT.wo males and two females ineach of the 0, 0.15 and 0.75 mg,/kg/daydosed groups were followedfor one year aftercessationof dosing coobserve depuation of compound and reversibiliotfy effects.'nere were no recovery qnirn2iisn the0.03 mgikg/day dose group. This reportcoversthe26 weeks of dosing. A separatereportwilldetailthefindingsfrom 52 weeks of recovery.Effectsoccuringin the 0.75 mg/kg/day dose group which are believedtobe compound relatedinclude:1) severeiunessof two males which died or were sacrificeidn etrremiswithin lastmonth of treaunerit2;) lower body weight inmales and females;3) increasedliverweight and hepatocelltl:hayrper-trophyand vacuolationinanimals;4) loweringof senim cholesteroli-ncorrelationto increasingserum PFOS levelsduringtreatment;5) lowered trfiodothryonin(e,-3)valuesinboth males and females;6) lowered est,-adi(oEl2) levelsinmales, No significanctompoui-id-relatefdfectswere observed in noakey s t.TeaLewdith 0.03 or 0,15 mqCf, kgjdav over 26 weeks . Ser-uinPFOS values@ncrease(i linearlyto an average of 18 and 90 in the 0.03 and 0.15 rni@i'kg/ddaoyse groups,respectivelyT.he i.-icreaisneserum PFOS inthe 0.75 mgfkg,/daydose group was not lineardurina the dosing period and reached an average of '215ppm after26 weeks of dosing.Liver PFOS levelsaveraged 25, 80 and 415 ppm for 0.03,0.15, and 0,"75miz/kg/daydose groups, respec@vely.Cholesterolvalues returnedtopredose levelswithin36 days of recovery,withoutcorrelationtoser--umPFOS. Serum PFOS had an apparentclimina6on half-lifoef '.17a5nd 1.18days over the firstsix-monthsof -ecovervin the 0.15 and 0,75 mg,,k2,,daydose groups, respectivelyT.he decreaseintotalserum chelesteroiobserved in high-dose arimals ,k,acsonf-trineacsi the earliesmteasurable clinicalresponse. The lower;,ngof totalserum c@iolesteroolccurred o:@v at serum PFOS conc-,,itriaotnsgreaterthan ICO ppm. The biologicalresponses obser-vedinthisstudy are consistentwith pr,,orodent and monkey studiesx@lththe exc,-ptionthat @;epatocellulap,eroxisome proldferationa,s observed in rodents,was not ol,)serveicn-tIhisstudy. Eealth effectshave not been observed from yearsof medical moriitorinaof 3NI chem@cal workers with occupationalexposure resultinginavera2c set= concentrationosf appro.,cimarlo-nley totwo ppm, and genera,illyessthan six ppm (Olsen et a].,JOENI Sept.,1999). -ihere,"oraeo,r,.-,Dccupationaelxlpyosed populationswith pooled average serum PFOS concentrationsthatare one to wo orders of magnitude lower than average worker se-= concentration(s3NI, "Perlllucrooct-aSruelf(DnateC@urrentSummary of HLunan Sera,Health ar.,Tdoxicology Data",January 21, 1999) have a mar,-:Lon"safet-Yof 103 to 104 With rlspectto the firstclinicall-yntasurablebiologicalresponse to ,3e:-flLioreocls@LaInfecnar@e-xposure, cholesterolowering.