Document 3Q4kkezkyMm6v5LL0J0X1QLVE

"rom: USII2388--VM01 To: US065823--USSP01 US265515--ALLINI ei er BEI00008--DIEVMB BUTENHOFF, JOHN ZOBEL, LARRY R. COX, BOB Date and time US088010--USSP01 M US312588--ALLINI 10/12/95 03:52:07 ZIMMERMAN, DALLAS MANDEL, JEFF Fron: Roger 0. Parking an Gaps FC 1225/2 From: Roger G. Perkins 3M 612/733-3Z22 PTP..oOOx..icoBBOOlXXogy333322S22e00rviSSttc..esPPaaMuuelld,,icaMMlNN 5D5e55p11t33.33--33322M2200Center, 220-2E-02 SSuubbjjeecctt:: AAPPMMEE MMeeeettiinngg Feavy The October i0, 1995 meeting of the APME Toxicology Committee was heldat the APME offices in Brussels; G. Malvinerno (Ausimont), R. Jung (Hoechst), G. Kennedy (duPont), M. Mistrorigo (Miteni), C. Elcombe (ICI), D. Farrar[ICI), Bob Cox (3M) and this writer were present. ICI toxicologists are very strongly espousing the position that APFO is an animal carcinogen based on the tumors in the liver, pancreas and testis seen in the duPont study in male rats only at a dose of 300 ppm in the diet. They and others present contend that the benign tumors are simply early lesions on a continuum that ultimately leads to malignant tumors. (I do not agree with their interpretation and stated this.) Most of the other issues discussed hinge in part on this first issue. They are still very strongly in favor of 3M publishing data in a peer reviewed journal that would put the Gilleland October 1993 publication into the proper Shee perspective. They would like for 3M to organize an effort to get the epidemiologists and physicians from the various companies in contact with each other. We spent a considerable time discussing the in-vitro testing for genotoxicity. I explained that 3M testing of FC-143 was delayed because of prioritization in a larger toxicity testing plan. The occurence of peroxisome proliferation was discussed in terms of the liver tumors and the relevance to man. There is some puzzlement about the mechanism for occurence of the acinar tumors, but Cliff Elcombe did remind us that the acinar cells and hepatocytes have a common embryonic origin and that some tumors in the acinar cells have an appearance very similar to hepatic cell tumors. The topic of APFO as an endocrine disruptor was raised and the statement made that the committee or producers need to develop a position paper on this issue. There was discussion of mechanistic considerations related to tumor formation. This included a proposal that Elcombe outline an approach to look at acinar cells in culture as regards APFO effects on cell proliferation, etc. I mentioned our study in progress of rat and human liver in culture and responses to several FC. There was interest in whether peroxisome ERG proliferation would be studied. Those persons representing APFO users. axe vary anxious for the ARTO Those persons representing APFO users are very anxious for the APFO manufacturers to make a decision on EU labeling of APFO and specifically are speculating whether risk phrase R40 applies. One action point is to get the 3M environmental data and duPont environmental data collected into a single review to determine if data gaps exist. The next meeting is proposed to occur during the week of January 15, 1996; location possibly Rome or Brussels. Exhibit 2547 22554477..00000011 3MA10024469 s:3~iMinncmceiegthththeebmemeeneeettfiiinntgginBBoobbusCiCoonxxg aatnnhdde IIEChhEaaTvvOeeX ddfiiossrccuuumssssteeoddettshhteeabmlmeeieestthiinnagg..groIItutpaapwpphpeoeasarerssgtothahalatt wow3nooMuullmpddiegrhbbfetelutbtohhereenoeofpcpitrrtaeenppoaaiirrncaattuiiasoocinnindgoofftahneedeiittEihhCteesErrTOsXaaaltttfeseoccrhhaunnnmidicctaaorllelerasretetpepaoodbrrltticsohoomrrpoacucnrrgdiirsttoeeurrpiiinawahwdohdosioceccuhummgeeconnaulttrrent ttotnohoxaxitipcceoorsllfuoolcgguhyyoaraoanonpddcatpapepnoroossissiciisbblltayyhceideegccoooaattnlodoxxiioifcctsoolltoohseggayyltAsdPdaHatEtaaandtwwoooxruuiellclddoaltoebbegdeycssuoucmmmommmpaamorriuiitnzztdeeesdde..,inbuwIIttthicaathpphppaeetcaaurrrssrent wwgtoiihattalhth msssaoouycmhmaabnneayypfooaatstpthheeererrr.isiisssstuuheeessgooonanltthhofeeiirrtheaaggeAennPddMaaE ttthhoaaxtticosslooommegeyoottchhoeemmrritrrtooeuuett,e tbtoouttthhtiihssat goal may be faster. 22554477..00000022 33MMAA1100002244447700