Document zomDvBddNDBYr7K6oeoey6bYR

ATTACHMENT I 3 2004 S :22AM DUFON i L h G A l !VU. \!<i i cdMotdE. K ij:*as7it4o e3ha*iidatonB.m W in d e l s M a h x L a n e & M it t sw o d o ef, l l p 150 West 5 6 th Street N e w Y o r k . N .Y . lOOl TEL: (St31 2 3 7 .( 0 0 0 FAX: (HI21 s e a - I S (5 NEWBRUNSWICK. 1J PRINCETON,NJ STAFFORD, CT ONITASPRtNO,PL Septem ber 1,2 0 0 4 TSCA C onfidential Business Inform ation Center (7407M) EPA East - Room 1428 U .S. Environm ental Protection Agency 1201 C onstitution A venue, N.W . W ashington, D C 20004-3302 la d ie s and G entlem en: W e represent M IC Specialty Chem icals, Inc. Pursuant to Section 8(e) o f the Toxic Substances C ontrol Act (TSCA), we subm it on behalf o f our client a copy o f a report dated A ugust 2 3 ,2 0 0 4 to M iteni S.p.A by D r. Giovanni Costa o f the U niversity o f V erona describing a m eeting w ith 3M and du Pont to discuss biological m onitoring o f M iteni workers exposed to perQ uorooctanoic acid (PFOA). A D epartm ent M anager o f our client received a copy o f the m em orandum on A ugust 23,2004 during an overseas trip. M iteni is an Italian company w hich m anufactures PFOA in Italy. Our client im ports PFO A purchased from M iteni into the U nited States. In general, the inform ation described in the enclosed report appears to be favorable and o u r client does not know that any inform ation in the report indicates a substantial risk. H ow ever, our client is not in a position to make that determ ination and, therefore, decided to m ake the subm ission on a precautionary basis. Our client advises that the enclosed inform ation is the only inform ation which it has about the biological m onitoring described in the report. I f you have any questions, please call m e at 212-237-1140. Vezy truly yours, E E Srm g cc: H itosbi Jhada, Esq. Takehiro Fujim ura, Esq. M s. M arian Roach (10282443:!} Edward E. Shea V E P . . I 5. 2004' / 8: 22AM 0 ' P re f. G iovanni Coste Madie Chirurgo Spscia.ystain Medicina del Lavoro Cattedre H Medicina del Lavoro Universit degli Studi di Verona Pja li Nogarola, 15-37131 VERONA 8 (045) 553077 C.P, C5T GNN 47W11 D025A P.lVA0237309023 8 EGAL NV Spett. Direzione MITENI S.p.A. Trssino (VI) Verona, 23.08.2004 Report on the meeting held on Friday 20* and Saturday 21" 2004 at the Inn at Montchanin Village (Wilmington, USA) with 3M and DuPont delegations. I. Participants: - John Butenhoff - Geary Olsen -L any2obel - Peter Gillies - John Green - Gerald Kennedy - Robin Leonard - Robert Rickard - Giovanni Costa 3M, toxicologist 3M, clinical epidemiologist 3M, occupational health physician DuPont, expert in lipid metabolism DuPont, statistician Dupont, toxicologist DuPont, epidemiologist DuPont, toxicologist M iteni, occupational health physician 2 ,Background O n August 9th I have been invited by G. .Olsen (3M) to participate in this meeting, organised jointly with P. Gillies (DuPont), aimed at discussing the results o f the analysis of the data collected by me ax Miteni plant in Trissino, concerning the workers of the PF departm ent. I S:23AM DUPONT * Prof, Giovanni Costa Medico Chirurgo Spoeta, sta in Medicina dei Lavoro Cattecfra diMedicina dal Lavoro Universit dagli Stdi d Verone p,za l. Negatola. 15 - 37131 VERONA (045) S33877 C.F. CSTQNN 47M11 002SA P.IVA 0237308 023 8 LEGAL E N V T L*'~"'Ki l\U. tICj q A s it was been agreed last year in the ambit o f the APME-APFO ad hoc toxicological working group, Xhave started a scientific collaboration with them aimed at evaluating the data related to the periodical, biological monitoring o fMiteni workers exposed to PFOA. Despite the small num ber o f workers involved (compared to 3M and DuPont workers), such data were considered very helpful in understanding any possible interaction o f PFOA i* with human physiology, as such cohort o f workers has been checked regularly since 1979 by annnai medical examinations, integrated by several blood and urine analysis, hi the case of 3M workers, some workers (on voluntary basis) have been checked occasionaly (1993, 1996, 2000), whereas DuPont did not carry out regular checks o f such kind in the past, but it is now carrying on a general examination o f more than 400 workers, the results o f which are due by the end o f this year. Therefore, the statistical analysis of Miteni data was considered very useful for checking whether or not any pre-clinical adverse effect could de detected, in order to better address the checks o f larger groups at 3M and DuPont plants, and for further more detailed investigations on some specific biological parameters. So, in December 2003 (after discussion and agreement with M iteni general management in the meeting held in Frankfurt on November 21" ) 1 sent G. Olsen die first database o f the biological m onitoring o f M iteni workeis (in anonymous format) and, in February 2004, on occasion o f the SOT Conference held in Baltimore, I had a first meeting with them and other 3M and DuPont experts (see my report dated 29.03.04 and abstract below) for a preliminary analysis o f the data. Thereafter, we decided to integrate the dataset with some more specific analysis concerning the lipids metabolism, that I collected during the periodical, annual blood check carried out in Spring this year. Consequently, two months ago I sent G. Olsen and P, Gillies two updated datasets (still in anonymous form at), one concerning the biological data available since 1987 o f all exposed workers to PFO A , and the second one concerning the last blood analysis carried out in Spring 2004. 2 6 ''2to. Giovanili Costo Medico Chirurgo Specialista Ir. Medicina dai Lavoro Cattedra df Medicine del Lever Universit degli Studi di Verona P s a l. Nogarola, 15 - 37131 VERONA * (045) 533877 C.F. CSTGNN47M11 D025A P.1VA 0237309 023 8 EGAL civr- S. Prelim inary results o f the statistical analysis The analysis o f the first database was aimed at evaluating any possible abnormality o f biological parameters, occurred in the last 17 years, in relation to the PFOA blood levels measured in the last 4 years (2000-2003); the second one was aimed at comparing exposed and non-exposed workers to find out any difference that could be statistically associated to PFOA exposure. The statistical analysis, carried out by means o f appropriate statistical programs by DuPont expert statisticians, confirmed (he negative results for almost all the 37 blood parameters considered: in particular no significant effects were detected as concerns haematology, proteins metabolism, immunology, liver, kidney and prostate function. Only some slight effects on lipids metabolism were detected, which deserve further analysis and proper interpretations. In fact, a slight increase o f total cholesterol in workers exposed to PFOA was observed, which also appeared to show an increasing trend associated with foe highest blood PFOA levels. Table 1 shows the comparison o f exposed and non-exposed workers and foe slight significant increase o f total cholesterol in exposed workers. There is no increase o f other lipids, such as tryglicerides in particular, but foe fraction o f "Non-HDL Cholesterol" seems that concerned. Figure 1 shows foe positive correlation between total cholesterol and PFOA blood levels in the last 4 years (when PFOA was measured): a slight association between PFOA blood Level and total cholesterol concentration seems to be consistent over foe years. Figure 2 shows foe same trend as concerns "Non-HDL Cholesterol". 3 7 S E U 5 . 2 0 0 4 " 8 : 2 3 AM DOPONT Fr, Giovanni Costa Medico Chirurgo Specialista In Mediana d6l Lavoro Cattedra Medicina del Laver Universit dagl!Stinti di Verona p.za 1. N ceats. 15 *37131 VERONA (045) 33377 C,F. CSTGNN47W11 D02SA P.IVA 0237309 023 8 EGAL E N V f IVU. 4 I Table 1: Comparison o f the main lipid components in exposed and non-exposed workers to PFOA E n d p o laa M aau& ctttrlaf Area Voir-P F O A PFOA Serum Lipids Tomi Cholesterol KDL Cholesterol LDL Cholesterol Non-KDL Cholesterol Noo-HOL/HPL Total Triglyecridcj 214 4 S3 1 133 3 16040 3.3 4 0 .2 |4 | 4 12 233 4 9 5142 146*8 182 4 1 0 3.9 4 0 J 169*19 P c a o g n p b Jc Characteristics Age BMI Alcohol Consumption 394 4 1.0 2SJ 03 037 4 0.02 40.7 4 14 25.7 4 0 4 0.36 * 0.04 P-valve 0.03 0.37 om 0.03 0.09 0.22 0.53 042 OJ37 Values ire expressedasthe mean * SEM fer*pproximwelyn= 94non PPOAworkets andB 35 PFOA *aVos Data ire from1 2004 samplecollection 4 8 i!5C. zUAuA4f A o: 2A5MAM_v_ DURONI " Prof. Giovanni Costa Medica Chirurgo S p ed an te in Medicina dei Lavoro Cattedra di Mancina dal Lavora Universit dagli Sturi di Verona P x a l. Nogarela, 15- 37131 V5ROKA * (045) 533877 C-F.CSTQNN47M11 DQ25A P.IVA 0237309023 S LEGA iVU. ij<f ! Figure 1: Correlations b etw e en Total Cholesterol (log) and FFQA (log) levels ia the 4 years Figure 2: Correlations between non-HDL Cholesterol (log) and PFOA (log) levels is the 4 years ; I 5\ ! 9 I'JO'Jfli 8 : 23AM DUPONT , Prof. Giovaaai Casta Medico Chirurgo Specialists in Medians del Lavora Cattedrs df Medicine del Lavoro UnivarsliS tiegl! Stud di Vsfans P.za l. Nogsraia. 15-37131 VERONA S (0*5) 533877 C-F- CSX GNN 47M11 0025A P.IVA 0237300 023 6 ,CCJi HA;I NV iVJ. UH i In the light o f these findings, Q. Olsen (3M epidemiologist) reviewed the 3M datasets related to their surveys carried out in 1993, 1996 and 2000, and a preliminary analysis concerning cholesterol levels appears to be in agreement with the Miteni data. In other words, it seems that FFOA (probably only at high blood concentrations) can interfere with metabolism o f Cholesterol, in particular by increasing fee fraction of "NonHDL Cholesterol". Such findings need a precise interpretation, also because they are in contrast with the animal experimental data (rats), where PFOA causes a decrease o f cholesterol levels. That can be related to interepecies differences in drug metabolism, which are also raised for the different findings in carcinogenicity (it is carcinogen in rats, but not in primates and humans). In order to elucidate better fee possible mechanisms underlying such effect P. Gillies, DuPont expert on lipid metabolism, made an updated review o f fee current knowledge on lipids metabolism, trying to make some hypothesis about possible mechanisms. According to his analysis, such effect cannot be mediated by a PPARalfa mechanism (as suggested for rats), bur it is probably due to an interference with a protein (GEPT) able to transfer o f cholesterol in blood and liver. H e is going to have a deeper insight on such matter both by further discussion with the best academy experts on lipids and by a bio-molecular study concerning the nuclear receptors for such protein. 4. Com munication and regulatory aspects Robert Rickard (DuPont) said that is going to have a FYI ("For your information") meeting wife EPA next Wednesday, August 25. According to the TSCA Se rules he has to report to EPA any new data concerning possible toxicological characteristics o f PFOA DuPont may know, wife particular reference to human health. H e exposed his agenda, which includes an updating o f fee recent toxicological studies carried our at fee Haskell Lab concerning fee exposure o f rats and mice to linear, branched 6 /6 Prof. Giovanni Costa Medico Chirurgo Spscisiista in Medians d9l Uvaro Caffedro dl M Btfldns dal Lavora Uvlwrsit& degli Studl ttf Verona P ja I. Nssarels, 16 37131 VERONA *(045)533877 C.F, CST ONN47M11 D02SA P.iVA 023730$ 023 8 and m ixed Oinear/branched) PFOA, as well as the presentation of some ongoing studies, dealing with the health examination, o f more the 400 workers at DuPont "W ashington" plant in W est Virginia, and the review o f epidemiological data concerning mortality in general population o f W est Virginia. G. Olsen and L. Zobel (3M) will also communicate their epidem iological data concerning 3M workers at Decatur and Antwerp plants. In such agenda he would like to mention also some findings related to the data on lipid metabolism mentioned above, related to Miami workers, keeping anonymous the source of data. In particular, he would like to report die positive findings o f a long lasting medical surveillance o f workers exposed to PFOA, showing no effects on general health and also on biological parameters, concerning the main target organs and functions, except for a mild possible interference with lipid metabolism, which deserves further analysis. So, he asked me whether he ean report such data, in particular he would like to show one o r two charts related to the lipid parameters (such as figures 1 and 2) in his presentation, w ithout mentioning the source and the name o f Miteni, and without giving EPA any written docum ent As I replied that I could not deal with such request, but he must ask and get the formal perm ission from Miteax Management, due to the short time available he asked me to pass you such request in order to get your response (whatever it is) as soon as possible. W ith land regards Prof. Giovanni Costa 7 // 2 0 04 ft :j ftnii L E G A L .. Prof. G iovanili C osta Medico Chirurgo Specialista in Medicina del Lavoro CaSedra di Mstfldna dal Lavoro Universit degli Studi di Verona F.53l. Negarla, 15 - 37131 VERONA 8 (045) 533S77 C.F. CST GNN 4.7M11 D025A P.IVAC23730S 023 8 mr VU. i Abstract o f m y report dated 29.03.04 concerning the m eeting o fth e APME-APFO ad hoc toxicology groupo, held in Baltimore on M arch 24.03.04. S.2. Workers. The Chairman noted that most o f the companies represented in the WG bad commenced or were about to embark on a blood level monitoring programme in their current employees (Asahi Glass has just started it and asked me some advice concerning the parameters to be collected from the workers). He encouraged all companies to share their data in the way that M itsui and 3M had done in the past, and he also asked me to co ordinate the outcomes for the APME group; I gave him my willingness for that As also Asahi Glass is sending its sample to the German lab already used by Solvay, I suggested that all European should join this lab, provided that it is quite reliable, in order to lim it the factors that can confound the results. As concerns our data, t informed the group that we analysing them with reference to the interaction w ith lipid metabolism in collaboration with Geary Olsen (3M) and Peter Gillies (DuPont); see the enolosed report o f the meeting held at M arriott hotel on Wednesday morning w ith G. Olsen and J. Buthenoff (3M) and P. Gillies and G. Kennedy (DuPont). G. Kennedy confirmed that DuPont is starting its hiomonitoring according to the protocol he circulated to the group in die last week. On Wednesday evening I have been invited for a dinner by Lany Jansen (Lawyer) and Robert Rickard (Science Director) o f DuPont for exchanging information about the workers' biomonitoring (see attached report). Attachment 1. M eeting with G. Olsen and J. Butenhoff (3M toxicologists), Peter Gillies and J. Kennedy (DuPont toxicologists) On W ednesday 24* morning, I had a 3-hour meeting with with 3M and DuPont toxicologist to discuss the preliminary findings o f the data collected in MTTENI workers and concerning the possible interference o f PFOA with lipid metabolism. G. Olsen have carried out a preliminary statistical analysis o f the biochemical data related to year 2002 and 2003, which showed some possible slight effects on HDL and LDL cholesterol. P. G illies (DuPont expert on lipids) described the meaning o f the different blood lipid components and their possible interaction with PFOA A fter a long discussion and a careful analysis o f the present data, it has been convened to add further data to the dataset, in particular those related to the ongoing biomonitoring which is due to end by April. In this survey further analysis o f lipids and proteins (LDL.Cholesterol, APO-A2, APO-B, reactive C-pratein) have been added in order to clarify better such interaction. So, I agreed in sending them such new data by the end o f April and then start a deeper statistical analysis. The results are expected to be sent to a toxicology journal for publication by the end o f the year. S TOTAL P .1 0 /2