AR226-1486 ENVIRONMENTAL AND HEALTH ASSESSMENT OF PERFLUOROOCTANE SULFONIC ACID AND ITS SALTS August 20, 2003 Prepared by 3M in consultation with Jack Moore, D.V.M., DABT, Hollyhouse, Inc.
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Page 1 FINAL REPORT Epidemiology, 220-3W-05 Medical Department 3M Company St.
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Fraunhofer ITEM Final Report 01 G 00 0 02 [Appendices G] 28 Day Repeated Dermal Contact Study of 3M Test Articles in Sprague-Dawley Rats Page 1 of 12 Appendix G: Amendments and Deviations (Copies) Fraunhofer ITEM Final Report 01 G 00 0 02 [Appendices G] 28 Day Repeated Dermal Contact Study of 3M Test Articles in Sprague-Dawley Rats Page 2 of 12 Study Plan Deviation Study No.: 01 G 00 0 02 Date: 8.5.00 Deviation No.: 1 S ubject: Fabric conditioning Page: 8 Paragraph: 5,3.2 Change: In addition to the description in the study plan (paragraph 5.3.2, page 8) the fabrics were pre-conditioned w ith deionisized w ater (spray application).
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ftFU%-OHL BIOSEARCH, INC. p.o. box 8598 Philadelphia, Pennsylvania !
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New Datatiff AR.&3.6-062.5 Completion of two generation reproductive studies for perfluorooctane sulfonate and EpetFrfOluSoEro, oacntdancerossusl-ffoonsatetreinstgufdoyllow up to Pharmacokinetics during pregnancy studies Second species (rabbit) teratology study Completion of 180 day repeat dose study in primates with one year recovery 3M Medical Department March 7,2000 I Pending Two-year feeding studies EtFOSE - In-life done 4/2000 Perfluorooctane sulfonate - In-life done 4/2000 6 month and one year recovery after 180 day feeding study in primates ADME study in primates 3M Medical Department March 7,2000 Pending Human sera studies Health claims study Update mortality study Mechanistic and metabolic studies 3M Medical Department March 7,2000 3 ResultsFo- sRteerpirnogdSutcutidoines/Cross- N0.O4 EmLg/fkogr/dreopfrpoedruflcutiovreoeonctdapnoeinstuslfonate is Perinatal mortality is predominantly a pup effect rather than a maternal effect Effect on cholesterol metabolism is hypothesized mechanism - studies planned to test hypothesis 3M Medical Department March 7,2000 ResultsD-oPseriSmtuatdeyRepeat 0.15 mg/kg/d well tolerated for 6 months (apparent NOEL) Cholesterol level decreased at perfluorooctane sulfonate serum concentrations greater than 100 ppm (in the high dose group) 2 deaths in males at 0.75 mg/kg/d that were apparently compound relateyd At the high dose (0.75 mg/kg/d) body weight liver weight and liver morphology were affected 3M Medical Department March 7,2000 r Results - Sera Concentrations Perfluorooctane sulfonate serum concentrations increase linearly with dose in l8o3w-1a0n7dpmpmid) dose groups (16-20 ppm and Perfluorooctane sulfonate serum tchoencheinghtradtoisoengs rfooullpows, ewditahbmipahxaimsicumcurvvaeluiens at 250-300 ppm 3M Medical Department March 7,2000 Background "19O6r8ganic fluorine" reported in human sera in 3M medical surveillance from 1976 to present Aconmalpyosuesndfosrdsopseecaiffitcerflu19o9ro2o-rdgeatneicction limit less than 50 ppb in 1997 Mcoocncuutltepimpaltpeiooanrnaaarlllyyysseiesxrpfaroossamemd)hpfilsientsodr(nipcoeanrfn-ludorooctane sulfonate at less than 50 ppb 3M Medical Department March 7,2000 7 Background Various studies, including medical surveillance, done over the last 25 years In the last two years have used outside experts to identify needs and help define studies Have created Scientific Advisory Panel for additional review 3M Medical Department March 7,2000 2 Review - Data in Health Effects Paper ADME Metabolic precursors to perfluorooctane sulfonate Repeat dose feeding studies - rat and primate Genotoxicity Teratology 3M Medical Department March 7,2000 Review - Data in Health Effects Paper (Continued) Cross-sectional study of exposed employees Mortality study at production plant site Irnepterroidmucdtaivtae fsrtoumdy2-generation Interim data from new repeat dose primate study 3M Medical Department March 7,2000 10 Results The additional data does not suggest a health risk associated with the levels of perfluor loctane sulfonate found in the sera of occupationally or non-occupationally exposed employees, blood bank samples or commercially available serum. 3M Medical Department March 7,2000 //
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SRPT T-6295.8, T-6316.4, T-6868.2, T-7071.1, T-7132.1 DT15-B 3M MEDICAL DEPARTMENT, CORPORATE TOXICOLOGY Title: Comparative Molecular Biology of Perfluorooctanesulfonate (PFOS, T-6295), N-ethyl perfhiorooctanesulfonamido ethanol (N-EtFOSE, T-6316), N-Ethyl perfluorooctanesulfonamide (N-EtFOSA, T-6868), Perfluorooctanesulfonamido acetate (FOSAA, T-7071), and/or Perfluorooctanesulfonamide (FOSA, T-7I32) of in Rats and Guinea Pigs following Oral dosing.
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/MSH6-/Z3S Toxicological Summary PFOS Dietary Chronic Definitive Reproductive Study: Mallard Test Substance: Perfluorooctanesulfonate (PFOS) Structure: 1-Octanesulfonic acid, 1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluoro, potassium salt.
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Report EO1-1256 PFOS: A Reproductiun Study with the Mallard Study Title A nalytical Phase Report for PFO S : A Reproduction Study w ith th e Mallard Data Requirement FIFR A Subdivision E, Section 7 1-4 O E C D Guideline 206 Author Lisa A.
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AR226-1864 it RESEARCH *, Proven Results
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0- 148.0 0- 309.0 0- 456.0 0 - 609,0 " Qz ID 2851.0 m 2589.2 m 2397.5 m 2310.1 ill Calibration Sample Name Weight (g BLANK XXXXXX) 148,0 1.0000 309.0 1.0000 450.0 1.0000 609.0 1.0000 765.0 1.0000 1000.0 1.0000 1508.0 1.0000 1713.0 1,0000 178B.0 1.0000 2275.0 1.0000 C-SPsak C-10 Peak Corrected | b Height Height c-a I Correlation 6818 235105 xxxxxxxx calc pk 428512 226285 421952 148.0 308043 237791 801150 281.0 1101968 221769 1095539 384.3 1432967 251095 1425688 500.1 1593255 260053 1585716 556.2 2033812 297132 2025199 2695213 223986 2688720 710.3 943.1 2956715 263653 2949072 1034.4 3129804 258813 3122301 1095.1 3755512 325203 3746085 1313.9 0 .0 b 1.0 Correlation C8 PPM calc pk 148.0 157.8 281.0 304.3 384.3 418.0 500.1 545.5 556.2 607.3 710.3 777.0 943.1 1033.3 1034.4 1133.8 1095.1 1200.7 1313.9 1441.7 13271.7 b 1.0 Correlation C8 PPM calc pk 157.8 162,5 304.3 320.6 418.0 443.4 545.5 581.1 607.3 647.9 777.0 831,2 1033.3 1107,9 1133.8 1216.5 1200.7 1288.8 1441.7 1549.0 32424.0 b 45663.6 i 1.0 Correlation 1.0 Correlation C8 PPM calc pk C8 PPM calc pk 162.5 320.6 443.4 16Z9 327.0 454.5 162.9 327,0 454.5 158.8 339.6 4B0.0 581.1 597.4 597,4 637.4 647.9 666.7 666.7 713.7 831.2 856.9 856.9 923.2 1107.9 1144.1 11144.1 1239,6 1216.5 1256.8 1256.8 1363.7 1288.8 1331.8 13318 144S.O 1549.0 1601.8 10018 174-J.o FP 1 FP 2 FP 3 FP 4 FP 5 FP 6 FP 7 FP 8 FP FP 10 FP 11 FP 12 FP 13 FP. 14 FP 15 FP 16 FP 17 FP 16 FP 19 FP 20 FP 21 FP 22 FP 23 0.5306 0.5750 0.5065 0.5217 0.5291 0,5956 0.6646 0.5183 0.5769 0.5649 0.5310 0.4958 0.5018 0.5064 0.5281 0.5117 0.5254 0.5367 0.5000 0.5530 0.5040 0.5030 0.5235 C-10 Peak Height Haight 365704 273494 707118 288431 509686 255687 124408 237885 468182 263369 92261 249360 794733 260443 866019 311955 832620 224096 623556 249217 442922 235366 686492 241814 785379 233470 149563 386431 162522 315010 67592 321813 84557 407816 310507 332929 243504 331220 376969 350166 126814 325285 83503 338561 195321 314340 Corrected | Qz 148.0 0 8 calc pk CSPPM 357776 125.5 236.5 698757 245.1 420.2 502274 176.2 347.8 117512 41.2 79.0 460547 161.5 305.3 85032 29.8 50.1 787183 276.1 415.4 856976 300.6 579.9 826124 289.8 502.3 616332 216.2 382.7 436085 153.0 288.1 879482 238.3 480.7 778611 273.1 544.2 138361 48.5 95.8 153390 53.8 101.9 58263 20.4 39,9 72735 25.5 48.6 300856 105.5 196.6 233902 82.0 164.1 366818 128.7 232.7 117384 41.2 81.7 73689 25.8 48.9 186209 65.313 127.63S 2 : 309,0 calc pk CSPPM 133.1 250.8 284.7 460.4 188.9 372.9 40.3 77.2 172.7 326.5 27.7 46.5 298.9 449.7 325.8 628.7 313.9 544.2 232.9 412.3 163.3 307.5 257.3 519.0 295.6 589.0 .48.3 95.4 54.1 102.5 17,4 34,0 23.0 43.7 111.1 206.9 85.2 170.4 136.5 246.9 40.2 79.8 23.3 44.2 66.790 130.52G Or 456.0 S i 609.0 calc pk C8PPM calc pk C8 PPM 135.7 255.8 135.1 254.6 277.9 483.3 282.7 4917 196.0 386.9 197.7 390.2 35.5 68.0 31.1 59.6 178.6 337.5 179.6 339.4 21.9 36.8 17.0 28.6 314.8 473.7 3210 4 3 3 .0 343.9 663.5 3512 077.6 331.0 573.8 337.8 585.6 243.5 168.4 431.1 317.1 247.0 169.0 437.3 318.3 269.9 544.3 274,4 553.4 311.2 44.2 620.2 87.3 317,3 40.1 79.2 50.5 10.8 16.8 112.0 84.0 139.6 35.4 95.5 2 1 .1 32.0 208.6 168.' 252.2 70.3 46.6 6.6 117 110.5 815 , 139.0 31.0 88.3 10.7 22.3 205.8 163.0 2514 618 17,2 32.6 64.143 125.353 1 2 .1 60.839 23,0 118.895 Qi 19/ .1 1/ JL -1 .9 332.9 o o l .0 loo.o 2816 o4o .o 2 3 .0 1010 RQ A \O ,0 "/ .3 AR226-2090 RJZ042298 765.0 Qz 1000.0 0- 1508.0 0- 1713.0 0- 1788.0 2097.3 m 1981.5 m 1754,7 m 1662.1 m 1639.1 88929.4 b 120271.9 b 203748.1 b 241791.6 b 251744.0 1.0 Correlation 1.0 correlation 1.0 co irelatior 1.0 correlation 1.0 CALIBRATION C8PPM c a lc pk C8 PPM c a lc p k C8PPM c a lc p k C8 PPM c a lc pk C8PPM NAME 158.8 152.2 152.2 124.4 124.4 108.4 108.4 103.8 103.8 339.6 343.6 343.6 340.5 340.5 338.5 336.5 335.2 335.2 480.0 492.2 492.2 508.2 508.2 513.7 513.7 514.8 514.8 637.4 658.8 658.8 696.4 69a4 712.3 712.3 716.2 716.2 713.7 739.5 739,5 787.6 787.6 808.6 806.6 813.8 813.8 923.2 961.3 961.3 1038.0 1038.0 1073.0 1073.0 1082.0 1082.6 1239.6 1296.2 1296.2 1416.1 1416.1 1472.2 1472.2 1486.8 1486.8 1363.7 1427.6 1427.6 1564.5 1564.5 1828.8 1828.8 1645.6 1645.6 1446.3 1515.0 1515.0 1863.2 1663.2 1733.1 1733.1 1751.3 1751.3 1743.8 1829.8 1829.8 2018.7 2018.7 2108.4 2108.4 2131.9 2131.9 148.0 309.0 450.0 609.0 765.0 1000.0 1508.0 1713,0 1788.0 2275.0 7350 E765.0 C8PPM c a lc 241.6 St p k C8 PPM c a lc 119.9 225.9 k pk C8PPM c a lc 87.8 165.4 pk C8PPM c a lc 69.8 131.5 St 1788.0 SAM PLE pk C8PPM NAME 64.7 121.9 F P 1 505.7 291.9 507.7 282.1 490.6 274.9 478.1 27Z7 474.3 FP 2 389.1 192,8 380.6 170.1 335.9 156.7 309.4 152.8 301.8 F P 3 28.1 -1.4 -2.7 -49.1 -94.2 -74.8 -143.3 -81.9 -157.0 FP 4 334.9 171.7 324.6 146.3 276.6 131.6 248.8 127.4 240.8 FP 5 -3.1 -17.8 -29.9 -67.7 -113.6 -94.3 -158.4 -101.7 -170.8 FP 6 501.0 706.6 336.6 371,8 506,4 717,3 332.5 372.3 500.3 718.2 328.1 370.1 493.7 714.1 326.7 369.2 491.5 FP 7 712.4 FP 8 609,3 356,2 617.5 354.7 614.8 351.6 609.4 350.4 607.4 FP 9 445.2 250.3 443.2 235.1 416.2 225.3 398.9 222.4 393.8 FP 10 311.7 159.4 300.1 132.4 249.4 116.9 220.1 112.5 211.8 FP 11 567.9 282.2 569.2 271.1 546.8 263.3 531.1 261.0 526.3 FP 12 655.3 332.2 662.1 327.6 65Z9 323.0 643.6 321.4 640.6 FP 13 46.5 9.1 18.0 -37.3 -73.6 -62.2 -122.9 -69.2 -136.6 FP 14 5B.2 16.7 31.6 -28.7 -54.3 -53.2 -100.7 -80.0 -113.6 FP 15 -28.6 -31.3 -61.2 -82.9 -162.0 -110.4 -215.8 -118.0 -230.7 FP 16 -14.7 -24.0 45.7 -74.7 -142.1 -101.7 -193.6 -109.2 -207.9 FP 17 188.3 91.1 189.8 55.3 103.1 35.5 66.2 30.0 55.8 FP 18 138.2 57.3 114.7 17.2 34.4 -4.7 -9.5 -10.9 -21.8 FP 19 239.6 124,4 225.0 92.9i 168.0 75.2 136.0 70.2 127.6 FP 20 26.9 -1.5 -2.9 -49.2!
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