Document KRXdKmJODoejp1R8nnDYvewko

@NtedicinHee,alth PhySiCS 3M CenterB,uilding220-2E-02 lndustri21 Hygiene, Toxico 'orgv PO Box 33220 -, - ,-V -- W 3M MediC21 Department St. Paul, MN 55133-3220 612 733 1110 Andrew M. Seacat, Ph.D. Senior Res. Toxicologist 3M Center, 220-2E-02 St.Paul,NIN 55133-3220 Phone: (651)575-3161 Fax: (651)733-1773 e-mail:amseacatl@mmm.com 5/3/1999 PeterJ.Thomford, Ph.D. Study Director,Toxicology Covance LaboratoriesInc. 3301 Kinsman Blvd.,Madison, WI 53704 Phone: 608-241-7202;Fax: 608-242-2736 Re: Covance 6293-225,T-6314.l.Finalization. Peter, The DraftReport forCovance No.: 6329-225,Title:13-Week DietaryToxicityStudy with N-Methyl PerfluorooctanesulfonamidEothanol (N-MeFOSE, T-6314.1)in Rats, cannot be finalized. The concern isover the conclusionthattheNOAEL isstatedtobe lessthan 3 ppm based on overallbody weight gain data(page 10).There was a decreaseinoverallbody weight means in males only atthe 30 and 100 ppm levels,and infemales only atthe 100 ppm level.Althoucyhthe body weight gainswere statisticalsliygnificantlryeduced at3 ppm, the questioniswhether or not thesearebiologicallsyignificanitnthe absence of decreased overallbody weiaht gainsat3ppm. Additionallytherewere no observable microscopicor clinicaclhemistry find1'0nosat3 ppm ineithermales or femalesthatwould supportthe conclusionof an adverseeffectator below 3 ppm. The conclusionthattherewas a body weiaht effectin males atthe 30 and 100 ppm levels and infemales atthe 100 ppm levelisvalid.The no observableadverseeffectlevel (NO,kEL) appearsto be lessthan30 ppm, whereas theno observableeffectlevel(NOEL) appears tobe lessthan 3 ppm takingintoaccount theapparent reduced weicrhtgain inthe 3ppm male and female dose groups.Pleasere-evaluatethisconclusion.Individualbody weig0ht trendsinthe ppm dose gt:rloups may need tobe analyzed fortrendsettingoutliers? Additionallyb,ut inthe same vein,the firsstentenceinthe second paracg@ raphunder "Body Weichts" on paae 23 shouldindicatethatbody welcrhtswere lowered formales given 30 and 100 ppm, not formales given 3 ppm, as thetrenddownward isnot si-nificanatnd isonly5 % which iswithinbiologicavlariation. Re2ards -1 Andrew M. SeacatPh.D. Study Monitor