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Appendix to TNO-report of 3M-02 Final version CONFIDENTIAL 04-12-2006 APPENDIX TO TNO-REPORT OF STUDY 3M-02 Project / study number: 031.10074 / 3M-02 TNO Quality of Life TNO Biosciences Gaubius laboratory Zemikedreef 9. P.O. Box 2215 2301 CE Leiden The Netherlands Phone +31 71 518 1209 Fax +31 71 518 1901 Authors: L H. Cohen E.J. Pieterman E Hoegee-de Nobel In assignment of: 3M. Medical Department Study monitor: John L. Butenhoff, Ph.D.. CIH. DABT Corporate Scientist Medical Department 3M Center, Building 0220-02-E-02 St.Paul, Minnesota 55144-1000 USA Phone: +1.651.733.1962 Fax: +1.651.733.1773 E-mail: ilbutenhoff@mmm.com Study director: Dr. Louis H. Cohen Status and Date: Final version: 04 December 2006 Previous versions: Draftl: 18 October 2006 Draft2: 30 October 2006 Number of pages: 172 Authorization by Dr. P.H.A. Quax, Technology manager of Vascular and Metabolic Diseases: Page A1 of A172 Appendix to TNO-report of 3M-02 Contents Contents Final version 04-12-2006 page A02 A. Code E3L mice before and after matching A03 B. Bodyweight and food intake measurements B1. Individual bodyweights B2. Food intake measurements A04 A04 A07 C. Plasma measurements C1. Plasma cholesterol measurements C2. Plasma triglyceride measurements C3. Pooled lipoprotein profile measurements C4. Pooled plasma ALAT measurements C5. Plasma ketone bodies measurements A13 A13 A15 A17 A24 A25 D. Measurements in metabolic cages D1. Code mice and metabolic cages D2. Average bodyweight mice in metaboliccages D3. Food and drink intake measurements D4. X activity measurements D5. O2 consumption,CO2 production and respiratory exchange ratio measurements D6. Energy expenditure A28 A28 A28 A29 A38 A41 A50 E. Fecal bile acid, sterol and fatty acid measurements A53 E1. Fecal weight measurements, bodyweight and food intake Measurements A53 E2. Fecal bile acid measurements A60 E3. Fecal sterol measurements A83 E4. Fecal fatty acid measurements A107 F. Intestinal cholesterol absorption A122 G. Liver weight, perigonadal fat weight and lipidcontents liver G1. Liver weight and perigonadal fat weight G2. Lipid contents liver A127 A127 A129 H. HMG-CoA reductase and cholesterol-7a-hydroxylase activity in liver microsomes and sterol-27-hydroxylase activity in liver mitochondria A136 H1. HMG-CoA reductase and cholesterol-7a-hydroxylase activity in liver microsomes A136 H2. Sterol-27-hydroxylase activity in liver mitochondria A148 I. Measurements in vitro experiment (rat hepatocytes) A156 Page A2 of A172 Appendix to TNO-report of 3M-02 Final version Appendix A. Code E3L mice before and after matching 1 mouse# cage# beforematching 658 86 663 86 712 93 716 93 752 98 758 98 763 99 784 102 790 102 791 102 641 84 645 84 646 84 674 88 737 96 738 96 740 96 760 99 765 99 785 102 650 85 678 88 690 90/91 699 90/91 729 95 754 98 756 98 759 98 766 99 793 103 681 89 686 89 704 92 705 92 706 92 710 92 768 100 771 100 792 103 795 103 665 87 666 87 667 87 671 87 679 88 700 90/91 730 95 731 95 744 97 799 103 714 93 721 94 727 94 769 100 774 100 776 101 778 101 782 101 783 101 797 103 652 85 657 86 670 87 680 89 687 89 696 90/91 720 94 724 94 761 99 762 99 excluded(655) 85 excluded(656) 86 excluded(741) 96 excluded(742) 96 excluded(748) 97 eartag LR 01 12 00 20 00 02 11 00 02 12 10 21 02 01 10 01 20 00 21 10 01 02 01 11 10 01 20 12 02 10 10 02 00 10 01 02 00 11 00 11 10 01 11 12 12 20 01 11 00 12 01 10 12 10 02 00 01 02 22 21 20 10 02 00 12 00 00 20 10 01 12 00 21 02 20 group# mouse# 1 cage# after matching 11 1 11 2 12 3 12 4 13 5 13 6 14 7 15 8 15 9 1 5 10 2 6 11 2 6 12 2 6 13 2 7 14 2 8 15 2 8 16 2 8 17 2 9 18 2 9 19 2 10 20 3 11 21 3 12 22 3 13 23 3 13 24 3 14 25 3 15 26 3 15 27 3 15 28 3 16 29 3 17 30 4 18 31 4 18 32 4 19 33 4 19 34 4 19 35 4 19 36 4 20 37 4 20 38 4 21 39 4 21 40 5 22 41 5 22 42 5 22 43 5 22 44 5 23 45 5 24 46 5 25 47 5 25 48 5 26 49 5 27 50 6 28 51 6 29 52 6 29 53 6 30 54 6 30 55 6 31 56 6 31 57 6 31 58 6 31 59 6 32 60 7 33 61 7 34 62 7 35 63 7 36 64 7 36 65 7 37 66 7 38 67 7 38 68 7 39 69 7 39 70 I 04-12-2006 Page A3 of A172 Appendix to TNO-report of 3M-02 Final version Appendix B. Bodyweight and food intake measurements B1. Individual bodyweights G roup M ouse# cage# r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in r u n in AVERAGE SD r u n in r u n in r u n in ru n in r u n in 641 645 646 650 652 657 658 663 665 666 667 670 671 674 678 679 680 681 686 687 690 696 699 700 704 705 706 710 712 714 716 720 721 724 727 729 730 731 737 738 740 744 752 754 756 758 759 760 761 762 763 765 766 768 769 771 774 776 778 782 783 784 785 790 791 792 793 795 797 799 84 84 84 85 85 86 86 86 87 87 87 87 87 88 88 88 89 89 89 89 90/91 90/91 90/91 90/91 92 92 92 92 93 93 93 94 94 94 94 95 95 95 96 96 96 97 98 98 98 98 98 99 99 99 99 99 99 100 100 100 100 101 101 101 101 102 102 102 102 103 103 103 103 103 exclu d e d (655) exclu d e d (656) exclu d e d (741) e x c 1u d e d (7 4 2 ) exclu d e d (748) 85 86 96 96 97 e a rta g LR 10 21 02 01 20 10 01 12 10 01 11 02 12 01 02 12 00 10 02 12 01 00 11 20 00 10 01 02 00 01 20 00 10 20 12 10 01 11 10 01 20 00 00 01 20 02 12 00 10 01 11 21 02 00 10 11 02 00 01 02 22 00 10 02 12 00 10 11 21 12 12 00 21 02 20 b o d yw e ig h t (g) w e e k -2 w e e k -1 week 0 3 0 .0 30.1 2 9 .2 2 7 .5 28.1 2 8 .7 3 1 .2 2 7 .5 -- 299-- 3 0 .9 2 7 .6 3 0 .0 3 0 .6 2 8 .5 311 3 1 .4 3 2 .6 3 0 .9 3 1 .8 3 2 .2 3 1 .9 30.1 3 0 .9 31.1 3 0 .5 2 5 .0 3 0 .7 2 5 .6 3 1 .3 2 5 .4 2 8 .0 3 0 .7 2 7 .7 3 1 .0 2 7 .9 3 1 .3 2 8 .6 2 7 .9 2 9 .9 3 1 .5 2 9 .9 3 1 .4 3 0 .0 3 1 .9 3 0 .3 2 9 .3 3 1 .4 2 9 .0 3 1 .5 3 0 .9 3 1 .5 2 9 .4 2 9 .2 3 0 .9 29.1 2 9 .9 2 8 .9 2 9 .6 29.1 3 1 .5 3 1 .4 2 6 .2 3 1 .0 2 6 .3 3 1 .8 2 6 .7 2 7 .6 2 7 .9 2 7 .8 2 9 .7 2 9 .0 2 9 .4 2 9 .7 2 9 .5 2 9 .2 3 1 .4 3 2 .0 3 0 .9 3 1 .9 3 0 .4 3 1 .8 2 4 .6 2 9 .4 2 4 .8 29.1 2 6 .4 2 9 .8 2 9 .0 2 9 .6 3 0 .2 2 8 .8 2 8 .2 2 8 .4 2 8 .8 2 8 .9 29.1 3 2 .5 2 7 .5 3 2 .6 27.1 3 1 .8 2 9 .0 2 6 .5 2 6 .9 2 8 .0 2 5 .0 2 9 .4 2 5 .3 2 9 .4 2 7 .0 3 0 .7 2 8 .8 2 8 .9 2 8 .5 2 9 .0 2 9 .3 3 0 .0 28.1 2 8 .7 2 8 .3 3 0 .6 2 7 .0 3 0 .9 2 7 .4 3 0 .9 2 7 .7 2 9 .0 2 8 .8 2 9 .4 2 9 .0 3 0 .5 31.1 2 8 .2 2 8 .0 2 9 .0 2 7 .8 2 4 .5 2 7 .3 2 4 .7 2 9 .3 26.1 2 5 .2 23.1 2 5 .7 2 3 .8 2 6 .4 2 4 .0 2 5 .5 2 5 .9 2 5 .5 2 5 .4 2 7 .2 2 5 .0 2 6 .8 2 5 .9 2 6 .5 2 8 .0 2 7 .0 28.1 2 7 .6 2 7 .9 2 8 .9 28.1 2 8 .2 3 0 .4 2 9 .0 2 7 .2 2 9 .3 27.1 2 9 .8 2 8 .0 2 5 .5 2 8 .2 2 5 .7 2 8 .3 2 5 .3 28.1 2 7 .5 2 7 .6 2 9 .0 27.1 2 8 .6 2 7 .0 2 8 .9 2 9 .5 2 8 .9 2 9 .3 2 8 .8 2 9 .7 2 8 .7 2 8 .8 2 9 .0 26.1 2 7 .4 2 6 .8 2 7 .5 2 6 .6 2 6 .0 2 7 .7 2 7 .8 2 7 .9 2 6 .8 2 9 .0 29.1 2 6 .7 2 9 .5 2 9 .4 2 6 .9 2 8 .0 2 9 .5 2 8 .4 3 28.51 2 9 .0 3 2 .0 3 1 .9 3 1 .9 3 2 7 .3 2 7 .0 2 8 .5 2 2 .2 2 2 .9 2 4 .6 2 9 .0 3 1 .0 2 9 .2 3 1 .6 3 0 .9 3 2 .2 3 0 .6 3 0 .9 3 1 .0 04-12-2006 Page A4 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Group Mouse# cage# 1 1 1 1 1 1 1 1 1 1 AVERAGE SD 2 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 4 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 7 AVERAGE SD 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 1 1 2 2 3 3 4 5 5 5 6 6 6 7 8 8 8 9 9 10 11 12 13 13 14 15 15 15 16 17 18 18 19 19 19 19 20 20 21 21 22 22 22 22 23 24 25 25 26 27 28 29 29 30 30 31 31 31 31 32 33 34 35 36 36 37 38 38 39 39 eartag LR 01 12 00 20 00 02 11 00 02 12 10 21 02 01 10 01 20 00 21 10 01 02 01 11 10 01 20 12 02 10 10 02 00 10 01 02 00 11 00 11 10 01 11 12 12 20 01 11 00 12 01 10 12 10 02 00 01 02 22 21 20 10 02 00 12 00 00 20 10 01 week 0 31.9 31.1 29.8 28.9 30.5 29.3 25.9 28.9 29.0 26.6 29.19 1 .8 5 29.2 28.7 30.6 31.9 30.0 28.3 30.9 26.4 26.5 28.8 29.13 1 .8 0 28.5 30.3 31.8 27.8 27.0 31.1 29.0 26.1 27.9 27.9 28.74 1 .8 2 30.9 29.1 29.2 30.4 31.8 26.4 28.9 29.8 26.0 26.9 28.94 1 .9 5 31.3 25.4 27.9 29.9 30.9 29.5 30.7 29.3 27.7 29.5 29.21 1 .7 8 30.2 31.8 28.0 30.4 28.0 25.3 28.1 29.0 29.5 28.0 28.83 1 .7 9 31.1 32.2 31.3 31.5 31.5 26.7 29.1 29.0 24.0 25.5 29.19 2.88 week 1 31.4 29.8 30.2 29.4 30.0 28.4 25.8 29.7 28.9 26.2 28.98 1.76 29.4 28.5 30.7 31.7 30.2 28.2 31.6 25.9 26.3 28.1 29.06 2 .0 3 27.4 29.2 32.4 27.8 26.3 30.8 30.1 26.4 27.5 27.8 28.57 2 .0 0 30.5 29.3 28.6 31.0 31.6 25.6 28.3 30.3 27.5 26.1 28.88 2 .0 4 29.5 24.7 26.9 29.4 29.4 28.4 27.9 27.9 26.3 28.0 27.84 1.53 29.2 31.2 27.1 30.8 28.0 24.8 27.8 27.7 29.8 27.5 28.39 1.91 30.1 30.2 28.8 30.6 30.4 26.2 28.2 28.4 23.4 25.2 28.15 2 .4 6 week 2 32.6 29.8 29.8 28.6 30.9 27.8 24.8 29.0 29.8 26.3 28.94 2 .2 4 29.8 28.9 30.3 32.3 29.7 29.4 31.7 25.9 26.5 28.8 29.33 2 .0 0 27.3 29.7 32.0 28.6 26.1 30.0 29.9 25.3 27.8 27.4 28.41 2 .0 3 30.2 29.2 29.0 31.6 31.4 25.6 29.1 30.7 28.0 26.3 29.11 2 .0 2 25.6 23.8 26.8 25.4 26.9 26.7 28.3 25.8 24.0 26.1 25.94 1.36 28.8 31.7 27.6 30.9 28.4 24.9 28.1 28.4 30.4 27.2 28.64 1.98 27.0 26.6 26.6 28.9 28.4 25.0 26.6 26.0 22.4 23.6 26.11 2 .0 0 w eek 2.3 25.0 23.8 26.6 25.0 27.0 26.5 28.4 25.6 24.6 25.3 25.78 1.35 26.9 26.4 25.2 27.7 27.3 24.5 25.6 25.4 21.7 23.6 25.43 1.82 week 3 32.5 29.8 29.6 27.9 30.5 28.1 25.0 28.6 29.7 26.2 28.79 2.15 30.2 29.0 29.3 31.7 30.2 29.6 31.7 25.6 26.8 28.2 29.23 1 .9 6 27.1 28.9 32.6 28.8 25.6 29.1 29.9 24.9 27.8 27.3 28.20 2.20 29.7 29.2 28.9 30.8 31.1 25.7 28.3 30.2 27.4 27.0 28.83 1 .7 4 25.6 24.8 27.0 25.7 27.9 27.9 28.4 28.0 25.4 27.0 26.77 1 .3 0 28.7 31.4 27.1 30.5 28.1 25.1 27.7 28.2 30.0 27.1 28.39 1 .8 5 26.2 25.0 24.7 27.8 27.1 24.6 25.5 25.3 22.3 23.5 25.20 1.61 w eek 3.4 28.0 24.8 27.3 27.5 29.1 28.6 29.5 29.7 25.2 27.6 27.73 1.67 26.0 24.1 25.0 27.7 26.8 25.2 26.2 26.0 23.1 24.3 25.44 1.37 week 4 32.6 29.9 29.8 27.9 30.4 27.6 25.7 28.1 29.2 26.1 28.73 2 .0 8 31.0 28.9 29.4 31.9 30.2 29.4 31.8 26.4 27.0 28.3 29.43 1.87 27.8 29.0 32.5 29.2 25.2 29.2 30.0 25.0 28.9 26.7 28.35 2 .2 7 29.7 28.9 28.9 30.9 31.1 25.3 28.2 30.6 27.5 27.3 28.84 1.83 27.5 24.2 26.7 28.1 28.9 28.4 29.2 29.3 25.7 27.8 27.58 1.63 28.3 31.3 27.1 30.3 28.8 25.1 27.9 28.9 30.6 27.2 28.55 1.87 26.3 24.7 25.3 27.9 27.1 25.3 25.8 26.1 22.8 23.8 25.51 1.50 Bodyweight (g) w eek 5 w eek 5.3 w eek 5.6 32.9 33.9 33.9 30.5 31.2 30.5 30.7 30.4 31.0 28.7 28.1 28.2 31.1 31.1 30.6 29.6 29.5 29.4 26.5 26.7 27.2 30.0 30.4 30.6 30.5 27.1 30.6 27.2 31.0 27.3 29.76 1 .9 0 29.91 2.14 29.97 2 .0 2 31.4 33.0 33.1 29.4 29.8 30.0 29.9 31.2 32.0 32.9 32.8 33.1 31.0 30.2 30.8 30.1 31.0 29.8 32.9 32.8 32.8 26.2 26.5 26.6 26.6 26.9 26.6 28.6 29.0 28.8 29.91 2.31 30.29 2.33 30.38 2 .4 8 28.2 27.8 28.3 28.8 28.8 28.9 32.9 32.2 32.3 28.9 28.8 28.9 25.8 25.8 26.3 29.0 28.7 28.5 30.2 30.1 30.1 25.1 25.0 24.7 29.2 27.1 29.0 27.0 29.7 27.0 28.52 2.21 28.32 2.07 28.47 2 .1 2 30.2 29.3 30.3 29.3 30.2 29.2 28.8 29.2 28.9 30.4 30.9 30.7 30.7 31.0 30.7 25.3 27.3 25.6 27.0 25.8 26.7 30.2 30.2 30.2 27.1 27.7 27.2 27.5 27.7 27.7 28.68 28.89 28.73 1 .8 0 1 .8 2 1.78 28.6 28.9 30.0 25.0 25.2 25.3 27.4 27.6 27.8 28.2 28.5 28.1 29.2 28.6 29.7 28.2 28.5 28.6 30.3 30.3 30.1 29.3 29.3 29.9 26.5 27.3 27.2 28.0 27.7 28.7 28.07 1.51 28.19 1 .3 7 28.54 1.52 28.5 28.4 28.5 31.5 27.4 31.3 27.3 31.5 27.2 30.3 30.2 30.0 28.7 28.8 28.4 25.5 25.6 25.4 27.6 28.9 27.6 29.1 27.8 29.1 30.4 26.8 30.3 26.7 30.7 26.7 28.56 28.53 28.53 1 .8 2 1 .7 7 1.87 28.0 28.2 27.7 27.2 26.1 27.3 26.2 26.7 26.6 28.3 28.2 28.5 27.4 27.4 28.2 26.1 26.1 26.1 26.2 26.0 26.2 26.5 22.8 26.7 23.6 26.9 23.0 24.6 25.1 24.6 26.32 26.48 26.45 1 .6 4 1 .4 2 1.65 week 6 32.9 30.1 30.0 28.3 29.2 30.4 26.3 30.0 30.5 27.0 29.47 1.89 32.2 30.0 31.2 33.6 30.1 30.0 32.5 26.3 26.9 29.0 30.18 2 .3 4 28.4 29.2 32.3 29.2 26.1 28.8 29.8 25.1 29.4 27.6 28.59 2 .0 0 29.6 28.7 29.6 30.5 30.7 26.2 26.9 30.1 27.2 27.7 28.72 1.62 29.1 25.5 28.6 28.8 30.1 28.6 30.1 29.7 27.0 28.4 28.59 1.42 28.7 31.4 27.0 29.7 28.0 25.3 26.9 28.8 30.9 26.3 28.30 1.99 29.1 27.8 26.8 28.9 27.6 26.2 26.7 27.2 23.6 25.7 26.96 1.60 w eek 6.3 33.2 30.2 30.2 28.4 31.1 29.6 26.5 30.8 30.7 27.1 29.78 1 .9 9 32.8 30.0 31.8 33.1 30.3 30.9 32.7 25.9 26.5 29.1 30.31 2.53 29.1 29.2 32.5 29.3 26.4 29.1 30.2 25.4 29.6 27.8 28.86 1 .9 8 29.9 29.2 29.8 30.5 31.1 26.5 28.0 30.9 27.5 27.5 29.09 1.61 29.8 25.6 29.2 29.1 29.6 28.6 30.6 30.2 27.3 28.6 28.86 1 .4 8 28.7 32.1 27.4 30.2 28.5 25.6 27.2 28.6 30.6 26.6 28.55 1 .9 8 28.5 27.8 27.0 28.7 28.2 27.1 26.7 27.3 23.8 25.4 27.05 1 .5 0 week 7 33.5 30.6 30.5 28.5 30.8 29.8 27.0 30.9 31.0 27.6 30.02 1 .9 0 33.1 29.5 32.0 33.0 30.4 29.5 31.4 26.2 27.7 29.5 30.23 2.23 29.9 30.1 33.2 29.3 27.2 29.4 30.3 26.3 30.4 28.9 29.50 1 .8 7 29.4 29.4 30.0 30.5 30.7 26.4 27.1 30.7 27.9 28.3 29.04 1 .5 4 30.5 25.9 29.6 29.1 30.6 30.2 30.0 30.5 27.2 29.0 29.26 1 .5 7 28.9 32.0 27.6 30.0 28.1 25.5 26.7 28.5 30.4 26.3 28.40 2.01 28.6 28.4 26.8 28.6 28.3 27.2 26.9 27.1 24.0 25.2 27.11 1 .5 3 week 8 33.8 31.2 30.2 28.6 31.0 29.7 27.5 31.0 30.7 27.3 30.10 1.94 34.1 29.5 32.2 33.7 29.9 30.5 31.2 26.4 28.7 29.7 30.59 2 .3 2 30.2 30.0 33.1 29.5 27.0 30.1 30.1 26.4 30.8 28.6 29.58 1.91 29.7 29.0 30.2 30.3 30.8 26.5 27.6 30.9 28.1 28.5 29.16 1.47 30.4 25.6 29.1 29.1 30.4 29.9 30.4 30.6 27.7 29.1 29.23 1.56 28.8 32.1 26.8 30.3 28.5 25.6 26.7 28.3 30.1 26.5 28.37 2 .0 3 29.0 28.6 27.1 29.1 28.6 27.3 27.2 27.6 24.3 25.7 27.45 1.53 w eek 8.4 33.7 31.0 30.3 28.5 30.8 29.9 27.3 31.9 30.6 27.1 30.11 2 .0 3 33.7 29.5 33.1 33.5 30.8 31.0 31.7 26.5 28.9 29.5 30.82 2 .2 9 30.5 30.1 33.2 29.3 27.2 31.0 30.3 26.1 31.1 28.5 29.73 2 .0 5 29.0 28.7 29.8 30.4 30.7 26.4 27.2 30.6 27.6 28.4 28.88 1.50 30.4 25.4 29.1 29.2 30.1 29.8 30.7 30.5 28.1 28.9 29.22 1.57 28.5 32.1 26.7 28.1 27.4 25.5 26.8 28.2 30.2 26.3 27.98 1.96 29.4 28.7 27.8 29.5 28.6 27.4 27.5 27.6 24.7 26.3 27.75 1.45 week 9 34.5 31.1 30.0 28.4 31.2 30.0 27.7 33.1 30.4 27.0 30.34 2.32 34.8 30.1 33.6 33.6 31.2 31.2 32.4 27.8 29.8 30.1 31.46 2.14 30.6 30.0 33.4 29.4 27.2 31.4 30.7 26.3 31.6 28.1 29.87 2.17 28.4 28.1 29.6 30.2 30.9 26.4 27.0 30.4 27.2 28.6 28.68 1 .5 5 30.2 25.0 28.9 29.3 29.6 29.7 31.0 30.4 28.5 29.0 29.16 1 .6 4 28.4 32.2 26.6 27.8 27.1 25.7 26.7 27.9 30.0 26.3 27.87 1 .9 5 29.7 29.2 28.2 29.8 28.9 27.8 27.6 28.0 25.0 26.8 28.10 1 .4 5 1 w eek 10 34.3 31.4 30.5 28.9 32.0 29.3 28.0 33.2 31.7 27.4 30.67 2 .2 6 35.4 30.6 33.3 33.8 30.6 30.7 32.9 28.3 30.8 30.1 31.65 2 .1 2 31.0 30.9 33.8 28.4 27.3 30.9 31.3 25.9 32.7 27.7 29.99 2 .5 4 28.2 28.1 29.2 29.6 30.3 26.2 26.7 29.7 26.8 28.1 28.29 1.41 31.3 25.4 29.6 29.4 29.5 30.0 31.2 30.7 28.4 29.0 29.45 1.70 27.8 31.3 26.2 27.7 26.8 25.2 26.7 27.6 29.9 26.0 27.52 1.85 29.8 29.5 28.0 29.8 29.5 27.9 27.5 28.1 25.1 27.6 28.28 1.45 Page A5 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 week 0 1 2 3 4 5 5.3 5.6 6 6.3 7 8 8.4 9 10 week 0 1 2 3 4 5 5.3 5.6 6 6.3 7 8 8.4 9 10 week 0 1 2 2.3 3 3.4 4 5 5.3 5.6 6 6.3 7 8 8.4 9 10 Bodyweight, p values Mann-Whitney U-test group 1 vs 2 group 1 vs 3 group 1 vs 4 group 1 vs 5 group 1 vs 6 group 1 vs 7 nn p nn p nn p nn p nn p nn p 10 10 0.739 10 10 0.481 10 10 0.853 10 10 0.796 10 10 0.529 10 10 0.631 10 10 0.912 10 10 0.631 10 10 0.971 10 10 0.075 10 10 0.393 10 10 0.631 10 10 0.796 10 10 0.579 10 10 0.796 10 10 0.004 10 10 0.631 10 10 0.011 10 10 0.631 10 10 0.481 10 10 0.912 10 10 0.019 10 10 0.739 10 10 0.001 10 10 0.436 10 10 0.631 10 10 0.912 10 10 0.218 10 10 0.912 10 10 0.002 10 10 0.971 10 10 0.143 10 10 0.247 10 10 0.029 10 10 0.165 10 10 0.001 10 10 0.739 10 10 0.105 10 10 0.218 10 10 0.063 10 10 0.143 10 10 0.002 10 10 0.739 10 10 0.123 10 10 0.143 10 10 0.075 10 10 0.165 10 10 <0.001 10 10 0.579 10 10 0.190 10 10 0.481 10 10 0.218 10 10 0.218 10 10 0.005 10 10 0.579 10 10 0.165 10 10 0.481 10 10 0.190 10 10 0.247 10 10 0.007 10 10 0.971 10 10 0.280 10 10 0.165 10 10 0.190 10 10 0.075 10 10 0.003 10 10 0.739 10 10 0.353 10 10 0.247 10 10 0.280 10 10 0.063 10 10 0.004 10 10 0.529 10 10 0.684 10 10 0.143 10 10 0.247 10 10 0.029 10 10 0.023 10 10 0.247 10 10 0.853 10 10 0.105 10 10 0.247 10 10 0.019 10 10 0.019 10 10 0.393 10 10 0.481 10 10 0.029 10 10 0.315 10 10 0.003 10 10 0.035 group 2 vs 4 group 2 vs 5 group 2 vs 6 group 2 vs 7 group 3 vs 4 group 3 vs 5 n n p n n p n n p n n p__ n n p nn p 10 10 0.912 10 10 0.796 10 10 0.579 10 10 0.579 10 10 0.739 10 10 0.529 10 10 0.853 10 10 0.143 10 10 0.353 10 10 0.481 10 10 0.631 10 10 0.853 10 10 0.796 10 10 0.001 10 10 0.353 10 10 0.005 10 10 0.393 10 10 0.007 10 10 0.684 10 10 0.005 10 10 0.280 10 10 <0.001 10 10 0.353 10 10 0.105 10 10 0.529 10 10 0.029 10 10 0.353 10 10 <0.001 10 10 0.684 10 10 0.393 10 10 0.280 10 10 0.043 10 10 0.247 10 10 0.001 10 10 0.631 10 10 0.631 10 10 0.247 10 10 0.035 10 10 0.123 10 10 0.001 10 10 0.393 10 10 0.796 10 10 0.190 10 10 0.075 10 10 0.105 10 10 0.002 10 10 0.579 10 10 0.912 10 10 0.165 10 10 0.089 10 10 0.075 10 10 0.004 10 10 0.684 10 10 1.000 10 10 0.218 10 10 0.075 10 10 0.105 10 10 0.009 10 10 0.579 10 10 0.912 10 10 0.218 10 10 0.039 10 10 0.089 10 10 0.003 10 10 0.912 10 10 0.853 10 10 0.165 10 10 0.190 10 10 0.052 10 10 0.002 10 10 0.853 10 10 0.853 10 10 0.035 10 10 0.075 10 10 0.011 10 10 0.002 10 10 0.315 10 10 0.436 10 10 0.009 10 10 0.015 10 10 0.002 10 10 <0.001 10 10 0.218 10 10 0.353 10 10 <0.001 10 10 0.035 10 10 <0.001 10 10 <0.001 10 10 0.105 10 10 0.579 group 3 vs 7 group 4 vs 5 group 4 vs 6 group 4 vs 7 group 5 vs 6 group 5 vs 7 nn p nn p nn p nn p nn p nn p 10 10 0.481 10 10 0.631 10 10 0.796 10 10 0.631 10 10 0.684 10 10 0.631 10 10 0.971 10 10 0.280 10 10 0.529 10 10 0.529 10 10 0.684 10 10 0.393 10 10 0.023 10 10 0.002 10 10 0.529 10 10 0.007 10 10 0.002 10 10 0.796 1 1 1 1 1 1 1 10 10 0.853 10 10 0.003 10 10 0.009 10 10 0.579 10 10 <0.001 10 10 0.043 10 10 0.023 1 1 1 1 1 1 1 10 10 0.007 10 10 0.011 10 10 0.165 10 10 0.579 10 10 0.001 10 10 0.353 10 10 0.011 10 10 0.029 10 10 0.393 10 10 0.912 10 10 0.011 10 10 0.579 10 10 0.015 10 10 0.043 10 10 0.315 10 10 0.529 10 10 0.009 10 10 0.796 10 10 0.007 10 10 0.015 10 10 0.579 10 10 0.796 10 10 0.015 10 10 0.912 10 10 0.007 10 10 0.052 10 10 0.796 10 10 0.739 10 10 0.035 10 10 0.631 10 10 0.035 10 10 0.023 10 10 0.631 10 10 0.481 10 10 0.019 10 10 0.529 10 10 0.005 10 10 0.003 10 10 0.853 10 10 0.353 10 10 0.029 10 10 0.190 10 10 0.003 10 10 0.019 10 10 0.739 10 10 0.315 10 10 0.035 10 10 0.165 10 10 0.005 10 10 0.043 10 10 0.529 10 10 0.165 10 10 0.143 10 10 0.089 10 10 0.019 10 10 0.052 10 10 0.353 10 10 0.165 10 10 0.481 10 10 0.063 10 10 0.063 10 10 0.123 10 10 0.089 10 10 0.190 10 10 0.912 10 10 0.035 10 10 0.075 group 2 vs 3 nn p 10 10 0.529 10 10 0.481 10 10 0.353 10 10 0.190 10 10 0.247 10 10 0.143 10 10 0.052 10 10 0.089 10 10 0.075 10 10 0.105 10 10 0.393 10 10 0.436 10 10 0.280 10 10 0.165 10 10 0.436 group 3 vs 6 nn p 10 10 0.579 10 10 0.912 10 10 0.796 10 10 0.912 10 10 0.971 10 10 0.971 10 10 0.796 10 10 0.971 10 10 0.684 10 10 0.579 10 10 0.218 10 10 0.218 10 10 0.063 10 10 0.052 10 10 0.043 group 6 vs 7 nn p 10 10 0.481 10 10 0.912 10 10 0.015 10 10 0.001 10 10 0.002 10 10 0.009 10 10 0.015 10 10 0.019 10 10 0.190 10 10 0.105 10 10 0.247 10 10 0.631 10 10 0.853 10 10 0.436 10 10 0.218 I I P<0 0 5 I Page A6 of A172 Appendix to TNO-report of 3M-02 B2. Food intake measurements Final version 04-12-2006 cage# 84 85 86 87 88 89 90/91 92 93 94 95 96 97 98 99 100 101 102 103 number of Food on cage Food off cage mice week -2 (g) week -1 (g) 3 86.1 37.1 3 88.8 41.6 4 117.2 49.1 5 131.5 51.8 3 84.2 22.9 4 105.6 29.3 4 108.5 40.9 4 107.7 49.6 3 79.3 21 4 104.1 40 3 82.6 25.7 5 132.8 40 2 54.5 20.8 5 139.5 57.2 6 156.4 78.2 4 105.8 30.5 4 102.2 40.3 4 102.3 44.7 5 132.2 53.6 days 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 Food intake (g/day/mouse) 2.72 2.62 2.84 2.66 3.41 3.18 2.82 2.42 3.24 2.67 3.16 3.09 2.81 2.74 2.17 3.14 2.58 2.40 2.62 2.80 0.32 Food on cage Food off cage week -1 (g) week 0 (g) 82 25 81.8 19.7 108.9 30.3 132.7 39.4 77.6 10.4 103.9 20.9 105.2 27.7 108.2 40.3 80.3 16.7 108.8 31.1 81.6 17.1 130.8 28.5 52.2 9.5 129.7 33.2 152.1 51.8 104.2 20.5 106.9 31 106.8 33.2 130.6 41.7 days 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 Food intake (g/day/mouse) 2.71 2.96 2.81 2.67 3.20 2.96 2.77 2.43 3.03 2.78 3.07 2.92 3.05 2.76 2.39 2.99 2.71 2.63 2.54 2.81 0.22 Page A7 of A172 Appendix to TNO-report of 3M-02____________ Final version__________________________04-12-2006 Page A8 of A172 Group 1 1 1 1 1 AVERAGE SD 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 AVERAGE SD 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 AVERAGE SD cage# 1 2 3 4 5 number of m ice 2 2 2 1 3 Food on cage week 0 (g) 70.8 69 62.5 31 86.1 Food off cage w e e k 1 (g) 34.8 26.5 26.4 12.5 38.3 days 6 6 6 6 6 63 71 83 92 10 1 85.8 38.3 89.4 59.8 34.1 34.1 15.3 31.4 28.6 18.2 6 6 6 6 6 11 1 12 1 13 2 14 1 15 3 16 1 17 1 34.4 35 63 32.2 84.1 29 30.9 17 16.4 24.3 13.5 31.3 12.6 12.2 6 6 6 6 6 6 6 18 2 19 4 20 2 21 2 62.4 110.6 54.5 65.1 20.9 47.6 12.5 29.8 6 6 6 6 22 4 23 1 24 1 25 2 26 1 27 1 108.8 29.5 29.6 53.8 32 32 48.9 10.7 11.6 17.5 15.9 14.9 6 6 6 6 6 6 28 1 29 2 30 2 31 4 32 1 36.1 59.2 60.2 108.1 40.5 16 20.1 20.7 44.7 23.6 6 6 6 6 6 33 1 34 1 35 1 36 2 37 1 38 2 39 2 33.3 33.8 40.8 56.5 30.8 50.5 55.7 14.2 14.8 23.1 16.1 14.5 18.1 25.1 6 6 6 6 6 6 6 Food intake g /day/m ouse 3.00 3.54 3.01 3.08 2.66 3.06 0.32 2.87 3.83 3.22 2.60 2.65 3.04 0.51 2.90 3.10 3.23 3.12 2.93 2.73 3.12 3.02 0.17 3.46 2.63 3.50 2.94 3.13 0.42 2.50 3.13 3.00 3.03 2.68 2.85 2.86 0.24 3.35 3.26 3.29 2.64 2.82 3.07 0.32 3.18 3.17 2.95 3.37 2.72 2.70 2.55 2.95 0.30 Food on cage w eek 1 (g) 51.4 52.3 51.1 29.7 83.6 Food off cage week 2 (g) 12 9.9 10.9 10.5 31.4 80.7 28.5 81.3 52.9 31.1 24.4 4.3 20.1 18 12.1 26.4 31.4 60 27.6 76.3 27.9 28.3 6.1 11.6 16.2 7.8 23.8 8.2 8.5 50.9 98.6 48.6 56.8 11.4 33.7 8.1 17.8 100.7 24.9 27.2 49.2 25.6 29.5 40.6 5.6 11.2 14.4 9 13 29 53.8 51.2 101.5 31.1 8.6 11.8 9.3 33 11.1 30.5 27.6 28.2 55.6 29.2 54.2 51.2 12.8 11.9 10.8 21 13.5 25.7 21.4 days 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 Food intake g/day/m ouse 3 .2 8 3 .5 3 3 .3 5 3 .2 0 2 .9 0 3 .2 5 0 .2 3 3 .1 3 4 .0 3 3 .4 0 2.91 3 .1 7 3 .3 3 0 .4 3 3 .3 8 3 .3 0 3 .6 5 3 .3 0 2 .9 2 3 .2 8 3 .3 0 3 .3 0 0.21 3 .2 9 2 .7 0 3 .3 8 3 .2 5 3 .1 6 0.31 2 .5 0 3 .2 2 2 .6 7 2 .9 0 2 .7 7 2 .7 5 2 .8 0 0 .2 4 3 .4 0 3 .5 0 3 .4 9 2 .8 5 3 .3 3 3 .3 2 0 .2 7 2 .9 5 2 .6 2 2 .9 0 2 .8 8 2 .6 2 2 .3 8 2 .4 8 2 .6 9 0 .2 2 Food on cage week 2 (g) 57.2 55 55.7 27.6 75.7 Food off cage week 2.3 days 77.6 27 83.1 55.5 31.8 29.9 29.4 56.3 30.5 81.6 35.1 30.1 57.4 106.4 53.4 52.3 108.7 31.7 31.3 57.8 30.3 34.1 83.2 23.7 24.3 41.4 23 27.4 2.8 2.8 2.8 2.8 2.8 2.8 35.1 57.4 50.2 104.6 36 37.6 32.4 31.1 54.6 33.9 55.7 56.4 30.8 24.6 24.8 41 28.1 44.7 44.5 2.8 2.8 2.8 2.8 2.8 2.8 2.8 Food intake g/day/m ouse 2 .2 8 2 .8 6 2 .5 0 2 .9 3 2.61 2 .3 9 2 .5 9 0 .2 6 2 .4 3 2 .7 9 2 .2 5 2 .4 3 2 .0 7 1.96 2 .1 3 2 .2 9 0 .2 8 Food on cage week 2.3 Food off cage week 3 (g) 15.2 9.3 19.2 5.1 17.4 8.7 9.6 16.5 17.3 10.2 17.5 7.9 8.4 10.3 25.2 15.3 10.1 15.7 24.9 10 11.6 108.6 27.2 31.8 57.1 29.5 31.0 62.5 14.9 20.1 31.1 15.5 17.8 14.3 10.3 7.1 25.2 17.8 32.9 33.6 27.6 52.5 28.7 54.9 60.0 23 24.2 16.6 26.7 18.5 34.5 26.7 days 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 4.2 4.2 4.2 4.2 4.2 4.2 7 7 7 7 7 4.2 4.2 4.2 4.2 4.2 4.2 4.2 Food intake g/day/m ouse 3 .0 0 3 .2 6 2.61 3.21 2 .7 8 2 .9 7 0 .2 8 3 .2 8 2 .4 9 3 .1 7 2 .7 3 3 .0 9 2 .9 5 0 .3 3 1.77 3 .0 7 3 .4 2 2 .8 9 2 .6 9 2 .8 3 2 .8 6 2 .9 4 0 .2 8 2 .9 8 2.91 3 .1 0 2.91 2 .9 7 0 .0 9 2 .7 4 2 .9 3 2 .7 9 3 .1 0 3.33 3 .1 4 3 .0 0 0 .2 3 2 .9 7 3 .3 6 3 .0 8 2 .8 4 2 .6 0 2 .9 7 0 .2 8 2 .3 6 2 .2 4 2 .6 2 3 .0 7 2 .4 3 2 .4 3 3 .9 6 2 .7 3 0.61 Food on cage w e e k 3 (g) 64.6 59.6 59.6 30.6 80.4 Food o ff cage week 4 (g) 28.8 21 21.2 10.7 30.8 days 6 6 6 6 6 77.4 30.1 79 54.3 33.5 19.5 8.4 18.5 19.6 14 6 6 6 6 6 31.3 32.8 67.6 27.4 78.4 32.9 30.2 11 13.7 24.8 9.1 26.5 14 11.5 6 6 6 6 6 6 6 56.7 110.8 55.6 59.1 18.7 46.9 16.2 23.1 6 6 6 6 104.1 38.5 40.3 65.1 35.3 31.3 30.4 22.5 19.7 21.8 18.8 12.3 6 6 6 6 6 6 29 54.5 54.8 105.1 29.5 9.5 16.3 19.1 39 11.1 6 6 6 6 6 50.1 41.5 31.5 60.4 27.3 52.7 58.5 32.1 23.3 13.4 28.1 8.2 18.4 28.1 6 6 6 6 6 6 6 Food intake g/day/m ouse 2 .9 8 3 .2 2 3 .2 0 3 .3 2 2 .7 6 3 .0 9 0 .2 3 3 .2 2 3 .6 2 3 .3 6 2 .8 9 3 .2 5 3 .2 7 0 .2 6 3 .3 8 3 .1 8 3 .5 7 3 .0 5 2 .8 8 3 .1 5 3 .1 2 3 .1 5 0 .2 5 3 .1 7 2 .6 6 3 .2 8 3 .0 0 3 .0 3 0 .2 7 3 .0 7 2 .6 7 3 .4 3 3.61 2 .7 5 3 .1 7 3 .1 2 0 .3 7 3 .2 5 3 .1 8 2 .9 8 2 .7 5 3 .0 7 3 .0 5 0 .1 9 3 .0 0 3 .0 3 3 .0 2 2 .6 9 3 .1 8 2 .8 6 2 .5 3 2 .9 0 0 .2 2 Appendix to TNO-report of 3M-02 Final version 04-12-2006 G roup cage# 1 1 1 1 1 AVERAGE SD 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 AVERAGE SD 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 number of m ice 2 2 2 1 3 3 1 3 2 1 1 1 2 1 3 1 1 2 4 2 2 4 1 1 2 1 1 1 2 2 4 1 1 1 1 2 1 2 2 Food on cage Food off cage w eek 4 (g) w eek 5 (g) 50.3 19.0 55.6 22.0 51.7 18.3 26.2 10.0 83.0 34.6 days 5.5 5.5 5.5 5.5 5.5 74.4 29.7 75.5 50.2 25.7 26.0 10.8 24.6 23.8 9.5 5.5 5.5 5.5 5.5 5.5 26.5 29.5 55.8 30.2 84.8 25.7 35.6 9.8 14.7 18.2 16.1 42.1 10.0 20.9 5.5 5.5 5.5 5.5 5.5 5.5 5.5 53.0 107.9 58.2 58.0 19.4 52.0 26.7 29.5 5.5 5.5 5.5 5.5 105.0 30.5 30.2 53.0 28.5 27.6 60.2 16.8 15.7 22.2 15.4 14.3 4.5 4.5 4.5 4.5 4.5 4.5 30.2 50.5 54.1 102.0 30.0 16.3 18.2 22.6 45.9 17.1 5.5 5.5 5.5 5.5 5.5 33.2 31.4 41.8 45.3 26.2 65.5 55.0 17.4 16.7 29.1 16.2 13.8 35.9 33.8 4.5 4.5 4.5 4.5 4.5 4.5 4.5 F ood intake g/day/m ouse 2.85 3.05 3.04 2.95 2.93 2.96 0.08 2.93 3.44 3.08 2.40 2.95 2.96 0.37 3.04 2.69 3.42 2.56 2.59 2.85 2.67 2.83 0.31 3.05 2.54 2.86 2.59 2.76 0.24 2.49 3.04 3.22 3.42 2.91 2.96 3.01 0.32 2.53 2.94 2.86 2.55 2.34 2.64 0.25 3.51 3.27 2.82 3.23 2.76 3.29 2.36 3.03 0.40 Food on cage Food off cage w eek 5 (g) w eek 6 (g) 60.2 22.1 60.7 19.5 57.2 16.8 31.6 10.7 77.1 19.2 85.4 37.4 85.2 51.9 33.6 19.8 12.4 14.2 13.6 13.4 36 37.4 55.9 35.4 89.8 27.4 31.2 15.7 16.2 7.1 15.6 32.7 8 9.4 57.7 106.9 53.4 57.7 16.5 33.2 11.1 17.7 109.2 41.4 32.5 61.1 32.8 31.6 32.3 20.1 10.6 15.5 12.5 10.2 36.3 60.8 52.6 105.5 34.8 16.6 20.3 12.3 36.7 16 33.2 35.4 39.9 78.1 31.1 61.2 52.9 12.7 16.3 20 38.8 12.1 24.9 15 days 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 Food intake g/day/m ouse 2.72 2.94 2.89 2.99 2.76 2.86 0.12 3.12 3.57 3.38 2.74 2.89 3.14 0.34 2.90 3.03 3.49 2.83 2.72 2.77 3.11 2.98 0.26 2.94 2.63 3.02 2.86 2.86 0.17 2.75 3.04 3.13 3.26 2.90 3.06 3.02 0.18 2.81 2.89 2.88 2.46 2.69 2.75 0.18 2.93 2.73 2.84 2.81 2.71 2.59 2.71 2.76 0.11 Food on cage w eek 6 (g) 78.3 73.4 67 38.3 94.8 Food off cage w eek 7 (g) 61.7 55.5 48.9 29.1 71 days 3 3 3 3 3 97.1 42 85.6 60.9 46.3 69.2 32.6 54.1 46.3 37.3 3 3 3 3 3 39.9 40.9 56.5 46.1 114.5 34.9 37.9 30.3 31.4 39.2 37.8 91.4 26.2 29.5 3 3 3 3 3 3 3 61.5 130.6 70 67.9 42.6 98.9 50.3 50.3 3 3 3 3 138.4 52.3 37.3 74.9 39.9 35.4 107.2 44.3 27.6 53.8 31.1 26.8 3 3 3 3 3 3 44.3 66.8 60 142 46.7 34.9 48.7 42.9 112.9 39 3 3 3 3 3 35.7 42.4 46.1 90.6 39.7 76.5 65.9 27.4 33.8 36.9 73.3 30.7 60.4 50.8 3 3 3 3 3 3 3 F ood intake g/day/m ouse 2.77 2.98 3.02 3.07 2.64 2.90 0.18 3.10 3.13 3.50 2.43 3.00 3.03 0.39 3.20 3.17 2.88 2.77 2.57 2.90 2.80 2.90 0.22 3.15 2.64 3.28 2.93 3.00 0.28 2.60 2.67 3.23 3.52 2.93 2.87 2.97 0.35 3.13 3.02 2.85 2.43 2.57 2.80 0.30 2.77 2.87 3.07 2.88 3.00 2.68 2.52 2.83 0.19 Page A9 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Group cage# mouse# Food on cage Food off cage days Food intake Food on cage week 7 (g) week 7.5 (g) g/day/mouse week 7.5(g) 11 1 438.1 428.4 3 3.22 29.8 1 MC 101 2 metabolic cage 20.3 1 MC 105 3 1 MC 201 4 metabolic cage metabolic cage 18.6 23.5 13 5 485.4 | 476.5 3 2.96 26.1 1 MC 206 6 metabolic cage 19.2 14 7 496.1 3 2.86 1 5 8,9,10 425.4 397.3 3 3.12 29.2 54.7 AVERAGE 3.04 SD 0.16 2 6 11,12,13 435 407.6 3 3.04 55.9 2 7 14 429.7 421.0 3 2.91 21.9 2 8 15,16,17 475.5 442.1 3 3.71 44.3 2 9 18,19 450.2 431.3 3 3.15 33.6 2 10 20 425.7 9.5 3 2.94 32.1 AVERAGE 3.15 SD 0.33 3 MC 102 21 metabolic cage 35.6 3 MC 106 22 metabolic cage 29.4 3 13 23 455.8 | 445.8 3 3.35 33.1 3 MC 202 24 3 14 25 metabolic cage 430.2 418.8 3 3.79 26.8 36.9 3 15 26,28 465.3 449.8 3 2.58 45.1 3 MC 206 27 metabolic cage 32.9 3 16 29 3 17 30 437.8 429.1 428.5 421.5 3 3 3.10 2.53 26.3 44.1 AVERAGE 3.07 SD 0.53 4 MC 103 31 metabolic cage 44.3 4 MC 107 32 metabolic cage 51.2 4 19 33,34,35,36 486.1 | 448.3 3 3.15 84.3 4 MC 203 37 metabolic cage 33.1 4 MC207 38 metabolic cage 32.6 4 21 39,40 436.2 419.7 3 2.75 44.2 AVERAGE 2.95 SD 0.28 5 22 41,42,43,44 505.9 470.3 3 2.97 109.2 5 23 45 443.9 434.1 3 3.26 41.4 5 24 46 438.7 428.7 3 3.35 32.5 5 25 47,48 443.3 423.9 3 3.24 61.1 5 26 49 5 27 50 428.6 436.1 419.7 427.5 3 3 2.98 2.86 32.8 31.6 AVERAGE SD 3.11 0.20 6 MC104 51 metabolic cage 38.2 6 29 52 432.6 | 424.2 3 2.81 27.6 6 MC 108 53 metabolic cage 33.1 6 MC204 54 metabolic cage 28.4 6 MC208 55 metabolic cage 33.1 6 31 56,57,58,59 409.8 371.4 3 3.20 87.4 6 32 60 441.6 433.5 3 2.69 21.7 AVERAGE SD 2.90 0.27 7 33 61 439.2 429.8 3 3.12 33.1 7 34 62 431.4 422.0 3 3.15 32.5 7 35 63 442.7 434.7 3 2.67 39.4 7 36 64,65 445.6 427.0 3 3.10 66.1 7 37 66 426.1 7 38 67,68 465.5 417.7 446.0 3 3 2.79 3.25 30.2 65.8 7 39 69,70 445.2 423.9 3 3.55 52.1 AVERAGE SD 3.09 0.29 NB: week 7-7.5: all mice are put on powdered food because of metabolic cages of part of mice Food off cage week 8 (g) 15.7 12.8 8.7 15.0 13.9 8.3 18.2 25.8 12.5 11.9 11.7 8.4 17.3 26.2 21.4 20.3 17.7 24.7 20.5 25.1 15.5 34.7 35.6 43.3 36.0 23.1 23.2 27.0 63.4 31.1 18.9 38.2 20.9 22.2 27.5 15.6 25.6 20.7 24.7 46.3 11.4 22.4 22.5 27.5 39.3 18.8 40.7 32.5 days 4 3 3 3 4 3 4 4 4 4 4 4 4 3 3 4 3 4 4 3 4 4 3 3 4 3 3 4 4 4 4 4 4 4 3 4 3 3 3 4 4 4 4 4 4 4 4 4 Food intake g/day/mouse 3.52 2.51 3.29 2.84 3.05 3.63 2.75 2.41 3.00 0.45 3.62 2.51 2.72 3.15 3.70 3.14 0.53 3.12 2.67 3.20 3.02 3.06 3.08 2.61 2.71 2.36 2.87 0.29 2.89 2.62 3.02 3.34 3.14 2.15 2.86 0.42 2.86 2.57 3.41 2.86 2.98 2.36 2.84 0.36 3.58 3.00 2.49 2.57 2.81 2.57 2.58 2.80 0.39 2.68 2.51 2.98 3.35 2.84 3.14 2.45 2.85 0.33 Page A10 of A172 Appendix to TNO-report of 3M-02 Final version G roup Mouse# cage# AVERAGE SD 2 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 4 4 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 7 AVERAGE SD 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 1 1 2 2 3 3 4 5 5 5 6 6 6 7 8 8 8 9 9 10 11 12 13 13 14 15 15 15 16 17 18 18 19 19 19 19 20 20 21 21 22 22 22 22 23 24 25 25 26 27 28 29 29 30 30 31 31 31 31 32 33 34 35 36 36 37 38 38 39 39 Food on cage Food off cage w e ek 8 (g) w e e k 9 (g) 34.3 27.1 11.7 5.8 28.6 7.9 44.1 24.6 36.9 43.3 15.6 20.5 42.2 22.2 34.2 10.1 33.0 32.9 12.1 8.6 days 7 7 7 7 7 7 7 7 7 7 34.1 36.5 28.4 29.5 28.3 27.1 36.0 44.3 45.2 33.9 9.5 16.4 6.3 11.4 5.8 3.2 15.9 22.2 25.0 9.3 7 7 7 7 7 7 7 7 7 7 34.0 35.1 29.8 27.6 44.1 44.3 47.2 34.9 33.2 32.6 12.0 14.2 7.7 8.2 18.8 23.4 26.3 13.8 13.1 12.6 7 7 7 7 7 7 7 7 7 7 33.1 34.2 45.7 36.0 45.7 44.1 36.9 32.1 22.5 33.4 11.5 15.5 24.8 14.0 23.0 25.6 17.2 10.7 1.2 12.3 7 7 7 7 7 7 7 7 7 7 44.1 37.7 45.1 44.2 35.6 43.2 44.8 42.5 29.6 34.3 19.5 18.9 21.2 25.6 15.2 19.8 26.1 18.6 7.9 15.6 7 7 7 7 7 7 7 7 7 7 33.9 32.4 35.6 41.8 42.1 44.0 43.3 32.5 28.2 29.4 10.7 14.6 18.6 19.9 22.0 23.1 23.1 9.8 7.1 12.0 7 7 7 7 7 7 7 7 7 7 34.4 45.2 30.1 29.8 27.2 33.4 31.5 46.2 44.1 32.5 14.3 21.3 8.8 7.7 3.8 12.5 10.2 26.1 23.2 14.4 7 7 7 7 7 7 7 7 7 7 Food intake g/day/m ouse 3.23 3.05 2.96 2.79 3.05 3.26 2.86 3.45 2.98 3.47 3.11 0.23 3.52 2.87 3.16 2.58 3.22 3.42 2.87 3.16 2.88 3.52 3.12 0.32 3.15 2.98 3.16 2.77 3.62 2.99 2.99 3.01 2.87 2.86 3.04 0.24 3.08 2.67 2.98 3.15 3.24 2.65 2.81 3.06 3.04 3.02 2.97 0.20 3.52 2.68 3.42 2.66 2.91 3.35 2.67 3.42 3.10 2.67 3.04 0.36 3.32 2.55 2.43 3.13 2.87 2.98 2.88 3.24 3.01 2.49 2.89 0.31 2.87 3.41 3.05 3.16 3.34 2.99 3.04 2.87 2.99 2.58 3.03 0.24 04-12-2006 Page A11 of A172 o (> O 01 01 Appendix to TNO-report of 3M-02 Final version 04-12-2006 week 0-1 1-2 2-3 (gr 5,7: 2.3-3) 3-4 4-5 5-6 6-7 7-7.5 7.5-8 8-9 week 0-1 1-2 2-3 (gr 5,7: 2.3-3) 3-4 4-5 5-6 6-7 7-7.5 7.5-8 8-9 week 0-1 1-2 2-2.3 2-3 (gr 5,7: 2.3-3) 3-4 4-5 5-6 6-7 7-7.5 7.5-8 8-9 Food intake, p va lu e s M a n n -W h itn e y U -test group 1 vs 2 group 1 vs 3 group 1 vs 4 group 1 vs 5 group 1 vs 6 nn p nn p nn p nn E nn 5 5 0.690 5 7 0.876 5 4 0.905 5 6 0.429 5 5 p 1.000 5 5 1.000 5 7 0.530 5 4 0.905 5 6 0.017 5 5 0.690 5 5 1.000 5 7 0.755 5 4 0.905 5 6 0.931 5 5 1.000 5 5 0.222 5 7 0.876 5 4 0.730 5 6 0.931 5 5 0.548 5 5 0.841 5 7 0.202 5 4 0.286 5 6 0.662 5 5 0.056 5 5 0.222 5 7 0.432 5 4 0.222 5 6 0.126 5 5 0.222 5 5 0.310 5 7 1.000 5 4 0.310 5 6 1.000 5 5 0.690 4 5 0.905 4 5 1.000 4 2 0.800 4 6 0.352 4 3 0.400 8 5 0.622 8 9 0.606 8 6 0.755 8 6 0.662 8 0 .4 6 3 10 10 0.912 10 10 0.529 10 10 0.353 10 10 0.579 10 group 2 vs 4 group 2 vs 5 group 2 vs 6 group 2 vs 7 group 3 vs 4 nn p nn p nn p nn p nn p 5 4 0.730 5 6 0.792 5 5 0.690 5 7 1.000 7 4 0.648 5 4 0.905 5 6 0.030 5 5 0.690 5 7 0.005 7 4 0.315 5 4 0.905 5 6 0.792 5 5 1.000 5 7 0.149 7 4 0.230 5 4 0.286 5 6 0.429 5 5 0.151 5 7 0.030 7 4 0.527 5 4 0.413 5 6 0.931 5 5 0.151 5 7 0.876 7 4 0.788 5 4 0.286 5 6 0.792 5 5 0.056 5 7 0.030 7 4 0.648 5 4 1.000 5 6 0.792 5 5 0.421 5 7 0.149 7 4 0.527 5 2 0.571 5 6 0.931 5 3 0.393 5 7 1.000 5 2 1.000 5 6 0.429 5 6 0.429 5 7 0.268 5 7 0.268 9 6 0.955 10 10 0.247 10 10 0.631 10 10 0 .165 10 10 0 .436 10 10 0.971 group 3 vs 7 group 4 vs 5 group 4 vs 6 group 4 vs 7 group 5 vs 6 n n p nn pn 7 7 0.805 4 6 J 0.476 4 1 I I I i i l7 7 0.001 4 6 1 0 .114 4 7~ 0.383 4 6 0.762 4 n 5 l5 5 pn 0.730 4 m0 .1 9 0 4 0.905 4 n ZJ 7 p 0.527 0.042 0 .2 3 0 nn p 6 5 0.329 1 16 5 0.017 6 5 0.931 7 7 0.026 4 6 0.610 4 5 1.000 4 7 0.527 6 5 0.931 7 7 0.318 4 6 0.352 4 5 0.413 4 7 0.315 6 5 0.082 7 7 0.073 4 6 0.171 4 5 0.413 4 7 0.230 6 5 0.030 7 7 0.535 4 6 0.762 4 5 0.286 4 7 0.315 6 5 0.429 5 7 0.755 2 6 0.429 2 3 1.000 2 7 0.667 6 3 0.167 9 7 0.918 6 6 0.699 6 7 0.445 6 7 0.836 6 7 0.836 10 10 0.684 10 10 0.631 10 10 0.529 10 10 0.739 10 10 0.315 group 1 vs 7 nn p 5 7 0.755 5 7 0.005 5 7 0.202 5 7 0.202 5 7 0.755 5 7 0.149 5 7 0.639 4 7 0.788 8 7 0.613 10 10 0.631 group 3 vs 5 nn p 7 6 0.295 7 6 0.002 7 6 0.445 7 6 0.836 7 6 0.366 7 6 0.445 7 6 0.731 5 6 0.931 9 6 0.607 10 10 0.796 group 5 vs 7 nn p 6 7 0.534 1 6 7 0.445 6 7 0.073 6 7 0.101 6 7 0.295 6 7 0.836 6 7 0.014 6 7 0.628 6 7 0.836 6 7 0.945 10 10 0.853 group 2 vs 3 nn 5T 7 5T T 5T T 5T T 5T T 5T T 5T T p 0 .6 3 9 0 .7 5 5 0 .6 3 9 0.432 0.432 0.432 0 .5 3 0 5 5 1.000 5 9 0.298 0 .4 3 6 group 3 vs 6 nn p 7 5 0.530 7 5 0.432 7 5 0.639 7 5 0.432 7 5 0.268 7 5 0.149 7 5 0.530 5 3 1.000 9 7 0.299 10 10 0.481 group 6 vs 7 nn p 5 7 _ 0.530 5 7 0.018 5T 7 5T T 5T T 5T T 5T T 3T T 77 0.202 0 .2 6 8 0 .1 4 9 1.000 1.000 0.667 0 .8 0 5 0 .3 1 5 p < 0 .0 5 Page A12 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Appendix C. Plasma measurements C1. Plasma cholesterol measurements group 1 1 1 1 1 1 1 1 1 1 AVERAGE SD 2 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 4 4 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 7 AVERAGE SD e x c lu d e d e x c lu d e d e x c lu d e d e x c lu d e d ex c luded Mouse# cage# 11 21 32 42 53 63 74 85 95 10 5 11 6 12 6 13 6 14 7 15 8 16 8 17 8 18 9 19 9 20 10 21 11 22 12 23 13 24 13 25 14 26 15 27 15 28 15 29 16 30 17 31 18 32 18 33 19 34 19 35 19 36 19 37 20 38 20 39 21 40 21 41 22 42 22 43 22 44 22 45 23 46 24 47 25 48 25 49 26 50 27 51 28 52 29 53 29 54 30 55 30 56 31 57 31 58 31 59 31 60 32 61 33 62 34 63 35 64 36 65 36 66 37 67 38 68 38 69 39 70 39 655 656 741 742 748 85 86 96 96 97 eartag LR 01 12 00 20 00 02 11 00 02 12 10 21 02 01 10 01 20 00 21 10 01 02 01 11 10 01 20 12 02 10 10 02 00 10 01 02 00 11 00 11 10 01 11 12 12 20 01 11 00 12 01 10 12 10 02 00 01 02 22 21 20 10 02 00 12 00 00 20 10 01 12 00 21 02 20 M easured cholesterol (m m ol/l) d ilu tio n week 0 week 1 week 4 week 8 week 0 week 1 week 4 week 8 week 0 3.219 2.814 2.172 2.211 2 2 3 3 6.438 3.446 3.088 2.599 2.394 2 2 3 3 6.892 3.633 3.176 2.120 1.725 2 2 3 3 7.266 3.260 2.556 1.911 1.877 2 2 3 3 6.520 1.847 2.612 2.042 1.733 2 2 3 3 3.694 3.819 3.458 2.033 2.500 2 2 3 3 7.638 4.055 3.958 1.815 2.166 2 2 3 3 8.110 3.949 3.668 2.347 2.295 2 2 3 3 7.898 4.590 3.257 1.972 1.816 2 2 3 3 9.180 3.706 3.015 1.911 1.854 2 2 3 3 7.412 7.10 1.45 3.998 3.901 2.625 2.181 2 2 3 3 7.996 1.791 2.145 1.110 0.867 2 2 3 3 3.582 4.428 3.281 2.094 2.287 2 2 3 3 8.856 4.274 2.878 1.859 1.353 2 2 3 3 8.548 4.453 3.080 2.443 2.272 2 2 3 3 8.906 1.774 2.306 1.057 0.837 2 2 3 3 3.548 1.750 2.322 1.563 1.209 2 2 3 3 3.500 4.079 3.450 2.233 2.151 2 2 3 3 8.158 4.055 2.959 2.233 2.439 2 2 3 3 8.110 3.633 3.233 2.085 2.029 2 2 3 3 7.266 6.85 2.33 4.201 3.217 1.850 2.439 2 2 3 3 8.402 3.446 3.007 1.876 2.021 2 2 3 3 6.892 4 .0 4 7 3 .2 5 7 2 .0 7 7 1.771 2 2 3 3 8.094 4.071 2.999 1.920 2.318 2 2 3 3 8.142 3.649 2.685 1.406 1.763 2 2 3 3 7.298 3.893 2.741 1.885 1.870 2 2 3 3 7.786 3.130 2.798 1.737 1.703 2 2 3 3 6.260 3.519 3.201 1.850 2.219 2 2 3 3 7.038 4.290 3.466 2.521 2.431 2 2 3 3 8.580 2.083 1.968 1.153 1.315 2 2 3 3 4.166 7.27 1.31 3.974 1.565 1.327 1.125 2 2 3 3 7.948 3.625 1.622 1.327 1.353 2 2 3 3 7.250 4.104 2.057 1.476 1.422 2 2 3 3 8.208 3.122 1.912 1.284 1.186 2 2 3 3 6.244 3.698 2.322 1.380 1.490 2 2 3 3 7.396 1.701 1.904 1.301 1.209 2 2 3 3 3.402 3.576 1.895 1.467 1.452 2 2 3 3 7.152 3.511 1.879 1.354 1.156 2 2 3 3 7.022 3.917 2.467 1.754 1.672 2 2 3 3 7.834 2.010 1.557 1.293 1.429 2 2 3 3 4.020 6.65 1.65 1.661 1.871 1.179 1.072 2 2 3 3 3.322 3.617 1.525 1.197 1.885 2 2 3 3 7.234 3.682 1.839 1.162 1.983 2 2 3 3 7.364 3.795 1.670 1.188 1.490 2 2 3 3 7.590 4.323 3.056 1.258 2.591 2 2 3 3 8.646 3.901 2.226 1.388 2.454 2 2 3 3 7.802 3.641 1.485 0.813 0.746 2 2 3 3 7.282 3.065 1.638 1.449 1.429 2 2 3 3 6.130 1.669 2.008 1.354 1.247 2 2 3 3 3.338 2.708 2.274 1.467 2.097 2 2 3 3 5.416 6.41 1.85 2.862 1.992 1.101 1.794 2 2 3 3 5.724 3.138 2.604 1.101 1.247 2 2 3 3 6.276 4.086 2.556 1.223 1.953 2 2 3 3 8.172 3 .3 1 6 2 .2 5 8 1.1 1 0 1.611 2 2 3 3 6.632 3.511 2.492 1.136 1.543 2 2 3 3 7.022 3.584 2.508 1.110 1.968 2 2 3 3 7.168 1.523 1.654 1.214 0.928 2 2 3 3 3.046 3.795 2.330 1.005 1.452 2 2 3 3 7.590 3.357 2.024 1.249 1.763 2 2 3 3 6.714 3.365 2.065 1.310 2.386 2 2 3 3 6.730 6.51 1.39 3.462 1.646 2.338 2.113 2 2 3 3 6.924 3.763 1.775 3.174 2.021 2 2 3 3 7.526 3.024 1.541 2.573 2.447 2 2 3 3 6.048 3.479 1.549 2.242 2.280 2 2 3 3 6.958 3.324 1.501 1.920 1.816 2 2 3 3 6.648 3.357 1.581 2.077 1.832 2 2 3 3 6.714 4.241 1.879 1.998 1.733 2 2 3 3 8.482 4.274 1.928 1.963 2.158 2 2 3 3 8.548 3.917 1.839 1.824 1.695 2 2 3 3 7.834 3.795 1.783 1.894 1.505 2 2 3 3 7.590 7.33 0.81 6.230 2 12.460 1.336 2 2.672 1.360 2 2.720 0.792 2 1.584 0 .7 7 6 2 1.552 C holesterol (m m ol/l) week 1 week 4 5.628 6.516 6.176 6.352 7.797 6.360 5.112 5.733 5.224 6.916 6.126 6.099 7.916 7.336 5.445 7.041 6.514 6.030 5.916 5.733 6.32 0.90 6.28 0.70 7.802 4.290 7.875 3.330 6.562 6.282 5.756 6.160 5.577 7.329 4.612 4.644 3.171 4.689 6.900 6.699 5.918 6.466 6.699 6.255 5.91 1.12 5.79 1.60 6.434 5.550 6.014 5.628 6.514 5.998 6.231 5.760 5.370 5.482 4.218 5.655 5.596 5.211 6.402 6.932 3.936 5.550 7.563 3.459 5.87 0.84 5.48 1.10 3.130 3.981 3.244 4.114 3.981 4.428 3.824 4.644 3.852 4.140 3.808 3.903 3.790 3.758 4.401 4.062 4.934 3.114 5.262 3.879 3.84 0.61 4.19 0.43 3.742 3.050 3.537 3.591 3.678 3.486 3.340 6.112 3.564 3.774 4.452 2.970 4.164 2.439 3.276 4.016 4.347 4.062 4.548 4.401 3.92 0.94 3.74 0.57 3.984 3.303 5.208 3.303 5.112 4.516 3.669 3.330 4.984 5.016 3.408 3.330 3.308 3.642 4.660 4.048 4.130 3.015 3.747 3.930 4.50 0.62 3.47 0.27 3.292 7.014 3.550 3.082 9.522 7.719 3.098 6.726 3.002 3.162 5.760 6.231 3.758 3.856 5.994 5.889 3.678 3.566 5.472 5.682 3.40 0.31 6.60 1.24 week 8 6.633 7.182 5.175 5.631 5.199 7.500 6.498 6.885 5.448 5.562 6.17 0.87 6.543 2.601 6.861 4.059 6.816 2.511 3.627 6.453 7.317 6.087 5.29 1.88 7.317 6.063 5.313 6.954 5.289 5.610 5.109 6.657 7.293 3.945 5.96 1.10 3.375 4.059 4.266 3.558 4.470 3.627 4.356 3.468 5.016 4.287 4.05 0.53 3.216 5.655 5.949 4.470 7.773 7.362 2.238 4.287 3.741 6.291 5.10 1.81 5.382 3.741 5.859 4.833 4.629 5.904 2.784 4.356 5.289 7.158 4.99 1.23 6.339 6.063 7.341 6.840 5.448 5.496 5.199 6.474 5.085 4.515 5.88 0.88 1 Page A13 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 week 0 1 4 8 week 0 1 4 8 week 0 1 4 8 group 1 vs 2 nn p 10 10 0.631 10 10 0.436 10 10 0.912 10 10 0.436 group 2 vs 4 nn p 10 10 0.247 10 10 <0.001 10 10 0.029 10 10 0.190 group 3 vs 7 nn p 10 10 0.739 10 10 <0.001 10 10 0.023 10 10 0.796 group 1 vs 3 nn p 10 10 0.631 10 10 0.393 10 10 0.035 10 10 0.796 group 2 vs 5 nn p 10 10 0.218 10 10 <0.001 10 10 0.015 10 10 0.796 group 4 vs 5 nn p 10 10 0.739 10 10 0.739 10 10 0.089 10 10 0.165 Plasma cholesterol, p values Mann-Whitney U-test group 1 vs 4 group 1 vs 5 group 1 vs 6 group 1 vs 7 nn p nn E nn p nn p 10 10 0.631 10 10 0.393 10 10 0.247 10 10 0.912 10 10 <0.001 10 10 <0.001 10 10 <0.001 10 10 <0.001 10 10 <0.001 10 10 <0.001 10 10 <0.001 10 10 0.853 10 10 <0.001 10 10 0.247 10 10 0.035 10 10 0.393 group 2 vs 6 group 2 vs 7 group 3 vs 4 group 3 vs 5 n n p n n p nn 10 10 0.190 10 10 0.529 p nn p 0.353 10 10 0.315 0000 10 10 0.009 10 10 <0.001 <0.001 10 10 0.001 10 10 0.007 10 10 0.579 0.005 10 10 0.002 10 10 0.579 10 10 0.853 <0.001 10 10 0.393 group 4 vs 6 group 4 vs 7 group 5 vs 6 group 5 vs 7 nn p nn p nn 10 10 0.393 10 10 0.654 p nn p 0.631 10 10 0.436 0000 10 10 0.015 10 10 0.052 0.052 10 10 0.247 10 10 <0.001 10 10 <0.001 0.089 10 10 <0.001 10 10 0.023 10 10 <0.001 0.853 10 10 0.315 group 2 vs 3 nn p 10 10 0.796 10 10 0.853 10 10 0.393 10 10 0.579 group 3 vs 6 nn p 10 10 0.123 10 10 0.001 10 10 <0.001 10 10 0.089 group 6 vs 7 nn p 10 10 0.190 10 10 <0.001 10 10 <0.001 10 10 0.089 p<0.05 1111 1111 Page A14 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 C2. Plasma triglyceride measurements group 1 1 1 1 1 1 1 1 1 1 AVERAGE SD 2 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 4 4 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 7 AVERAGE SD e x c lu d e d e x c lu d e d e x c lu d e d e x c lu d e d e x c lu d e d Mouse# cage# 11 21 32 42 53 63 74 85 95 10 5 11 6 12 6 13 6 14 7 15 8 16 8 17 8 18 9 19 9 20 10 21 11 22 12 23 13 24 13 25 14 26 15 27 15 28 15 29 16 30 17 31 18 32 18 33 19 34 19 35 19 36 19 37 20 38 20 3 9 21 4 0 21 41 22 42 22 43 22 44 22 45 23 46 24 47 25 48 25 49 26 50 27 51 28 52 29 53 29 54 30 55 30 5 6 31 5 7 31 5 8 31 5 9 31 60 32 61 33 62 34 63 35 64 36 65 36 66 37 67 38 68 38 69 39 70 39 655 85 656 86 741 96 742 96 748 97 e a rta g LR 01 12 00 20 00 02 11 00 02 12 10 21 02 01 10 01 20 00 21 10 01 02 01 11 10 01 20 12 02 10 10 02 00 10 01 02 00 11 00 11 10 01 11 12 12 20 01 11 00 12 01 10 12 10 02 00 01 02 22 21 20 10 02 00 12 00 00 20 10 01 12 00 21 02 20 M easured T G (m m ol/l) d ilu tio n week 0 week 1 week 4 week 8 week 0 week 1 week 4 week 8 0.445 0.387 0.257 0.298 2 2 3 3 0.467 0.270 0.263 0.266 2 2 3 3 0 .9 5 0 0.731 0 .2 9 0 0 .2 3 3 2 2 3 3 0.706 0.609 0.329 0.277 2 2 3 3 1.666 0.583 0.214 0.277 2 2 3 3 0.645 0.472 0.345 0.244 2 2 3 3 0.595 0.625 0.247 0.471 2 2 3 3 0.495 0.482 0.208 0.293 2 2 3 3 0.562 0.477 0.296 0.233 2 2 3 3 0.756 0.456 0.186 0.212 2 2 3 3 0.584 0.434 0.274 0.255 2 2 3 3 0.695 0.667 0.356 0.336 2 2 3 3 0.639 0.445 0.219 0.255 2 2 3 3 0.961 0.535 0.219 0.222 2 2 3 3 1.366 0.842 0.340 0.461 2 2 3 3 0.833 0.688 0.422 0.655 2 2 3 3 0.417 1.080 0.515 0.585 2 2 3 3 0.589 0.376 0.257 0.201 2 2 3 3 0.467 0.477 0.252 0.320 2 2 3 3 0.501 0.355 0 .2 1 4 0.195 2 2 3 3 0.573 0.276 0.121 0.190 2 2 3 3 0.606 0.307 0.148 0.201 2 2 3 3 0.978 0.762 0.307 0.233 2 2 3 3 0.661 0.932 0.372 0.168 2 2 3 3 0.795 0.456 0.143 0.190 2 2 3 3 0.656 0.482 0.148 0.244 2 2 3 3 0.478 0.376 0.143 0.152 2 2 3 3 0.528 0.382 0.137 0.195 2 2 3 3 0.412 0.403 0.208 0.336 2 2 3 3 0.900 0.673 0.312 0.369 2 2 3 3 0.856 0.244 0.137 0.082 2 2 3 3 0 .6 3 4 0.281 0 .1 4 3 0 .0 8 2 2 2 3 3 0.445 0.276 0.121 0.087 2 2 3 3 0.506 0.233 0.099 0.103 2 2 3 3 0.589 0.207 0.132 0.093 2 2 3 3 0.489 0.297 0.230 0.206 2 2 3 3 0.739 0.329 0.132 0.082 2 2 3 3 0.994 0.419 0.148 0.082 2 2 3 3 0.562 0.270 0.104 0.103 2 2 3 3 0.673 0.339 0.186 0.190 2 2 3 3 0.229 0.376 0.121 0.120 2 2 3 3 0.456 0.212 0.132 0.228 2 2 3 3 0.512 0.165 0.099 0.206 2 2 3 3 1.194 0.202 0.132 0.222 2 2 3 3 0.928 0.218 0.099 0.358 2 2 3 3 0 .6 3 4 0.181 0 .1 1 0 0 .3 2 0 2 2 3 3 0.722 0.260 0.247 0.309 2 2 3 3 0.678 0.207 0.208 0.250 2 2 3 3 0.589 0.323 0.870 0.103 2 2 3 3 0.551 0.186 0 .1 1 5 0.260 2 2 3 3 0.728 0.424 0.110 0.131 2 2 3 3 0.545 0.773 0.170 0.125 2 2 3 3 0.850 0.620 0.208 0.201 2 2 3 3 1.227 0.916 0.159 0.136 2 2 3 3 0.667 0.720 0.170 0.212 2 2 3 3 0.606 0.487 0.159 0.228 2 2 3 3 0.168 0.244 0.154 0.114 2 2 3 3 0.628 0.588 0.154 0.179 2 2 3 3 0.578 0.419 0.154 0.168 2 2 3 3 0.467 0.366 0.126 0.325 2 2 3 3 1.349 0.196 0.263 0.168 2 2 3 3 0.717 0.228 0.361 0.163 2 2 3 3 0.650 0.249 0.356 0.212 2 2 3 3 0.856 0.244 0.203 0.217 2 2 3 3 0.784 0.265 0.236 0.260 2 2 3 3 0.539 0.329 0.318 0.212 2 2 3 3 0.606 0.202 0.312 0.201 2 2 3 3 0.428 0.265 0.225 0.379 2 2 3 3 0.573 0.302 0.230 0.212 2 2 3 3 0.473 0.255 0.132 0.136 2 2 3 3 1 .9 5 4 0 .9 7 8 0 .9 1 7 0.251 0 .2 5 6 2 2 2 2 2 week 0 0.89 0 .9 3 4 1.9 1 .4 1 2 3 .3 3 2 1.29 1.19 0.99 1 .1 2 4 1 .5 1 2 1.46 0.73 1 .1 6 8 1.39 1 .2 7 8 1 .9 2 2 2 .7 3 2 1 .6 6 6 0 .8 3 4 1 .1 7 8 0 .9 3 4 1 .0 0 2 1.41 0.57 1 .1 4 6 1 .2 1 2 1 .9 5 6 1 .3 2 2 1.59 1 .3 1 2 0 .9 5 6 1 .0 5 6 0 .8 2 4 1.8 1.32 0.36 1 .7 1 2 1 .2 6 8 0.89 1 .0 1 2 1 .1 7 8 0 .9 7 8 1 .4 7 8 1 .9 8 8 1 .1 2 4 1 .3 4 6 1.30 0.35 0 .4 5 8 0 .9 1 2 1 .0 2 4 2 .3 8 8 1 .8 5 6 1 .2 6 8 1 .4 4 4 1 .3 5 6 1 .1 7 8 1 .1 0 2 1.30 0.53 1 .4 5 6 1.09 1.7 2 .4 5 4 1 .3 3 4 1 .2 1 2 0 .3 3 6 1 .2 5 6 1 .1 5 6 0 .9 3 4 1.29 0.54 2 .6 9 8 1 .4 3 4 1.3 1 .7 1 2 1 .5 6 8 1 .0 7 8 1 .2 1 2 0 .8 5 6 1 .1 4 6 0 .9 4 6 1.40 0.53 3 .9 0 8 1 .9 5 6 1 .8 3 4 0 .5 0 2 0 .5 1 2 T G (m m ol/l) week 1 week 4 0 .7 7 4 0 .5 4 0.771 0.789 1 .4 6 2 0.87 1 .2 1 8 1 .1 6 6 0.987 0.642 0 .9 4 4 1.25 1.035 0.741 0 .9 6 4 0 .9 5 4 0 .9 1 2 0.624 0.888 0.558 1.02 0 .2 6 0.79 0.16 0 .8 6 8 0.822 1 .3 3 4 0 .8 9 1.068 0.657 1.07 1 .6 8 4 0.657 1.02 1 .3 7 6 2 .1 6 1.266 1.545 0 .7 5 2 0 .9 5 4 0.71 0.771 0.756 0.642 1.18 0 .4 6 0.92 0.30 0 .5 5 2 0.363 0 .6 1 4 1 .5 2 4 0.444 0.921 1 .8 6 4 0 .9 1 2 1.116 0.429 0 .9 6 4 0 .7 5 2 0.444 0.429 0 .7 6 4 0.411 0 .8 0 6 1 .3 4 6 0.624 0.936 1.01 0 .4 3 0.61 0.27 0 .4 8 8 0.411 0 .5 6 2 0 .5 5 2 0.429 0.363 0 .4 6 6 0 .4 1 4 0.297 0.396 0 .5 9 4 0.69 0 .6 5 8 0 .8 3 8 0.396 0.444 0 .5 4 0 .6 7 8 0.312 0.558 0 .5 8 0 .1 2 0.43 0.12 0 .7 5 2 0 .4 2 4 0.363 0.396 0 .3 3 0 .4 0 4 0.297 0.396 0 .4 3 6 0 .3 6 2 0.297 0.33 0 .5 2 0 .4 1 4 0.741 0.624 0 .6 4 6 0 .3 7 2 2.61 0.345 0 .4 7 0 .1 4 0.42 0.16 0 .8 4 8 1 .5 4 6 0.33 0.51 1.24 1 .8 3 2 0.624 0.477 1.44 0 .9 7 4 0.51 0.477 0 .4 8 8 0.462 1 .1 7 6 0 .8 3 8 0 .7 3 2 0.462 0.462 0.378 1.11 0.41 0.47 0.08 0 .3 9 2 0 .4 5 6 0.789 1.083 0 .4 9 8 0 .4 8 8 1.068 0.609 0 .5 3 0.708 0 .6 5 8 0 .4 0 4 0.954 0.936 0 .5 3 0 .6 0 4 0.51 0.675 0.69 0.396 0.51 0 .0 8 0.79 0.22 week 8 0 .8 9 4 0 .7 9 8 0 .6 9 9 0.831 0.831 0 .7 3 2 1 .4 1 3 0 .8 7 9 0 .6 9 9 0 .6 3 6 0.84 0.22 0 .7 6 5 1 .0 0 8 0 .7 6 5 0 .6 6 6 1 .3 8 3 1 .9 6 5 1 .7 5 5 0 .6 0 3 0.96 0 .5 8 5 1.05 0.49 0.57 0 .6 0 3 0 .6 9 9 0 .5 0 4 0.57 0 .7 3 2 0 .4 5 6 0 .5 8 5 1 .0 0 8 1 .1 0 7 0.68 0.21 0 .2 4 6 0 .2 4 6 0.261 0 .3 0 9 0 .2 7 9 0 .6 1 8 0 .2 4 6 0 .2 4 6 0 .3 0 9 0.57 0.33 0.14 0.36 0 .6 8 4 0 .6 1 8 0 .6 6 6 1 .0 7 4 0.96 0 .9 2 7 0.75 0 .3 0 9 0.78 0.76 0.21 0 .3 9 3 0 .3 7 5 0 .6 0 3 0 .4 0 8 0 .6 3 6 0 .6 8 4 0 .3 4 2 0 .5 3 7 0 .5 0 4 0 .9 7 5 0.55 0.19 0 .5 0 4 0 .4 8 9 0 .6 3 6 0.651 0.78 0 .6 3 6 0 .6 0 3 1 .1 3 7 0 .6 3 6 0 .4 0 8 0.65 0.20 1 Page A15 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 week 0 1 4 8 week 0 1 4 8 wee k 0 1 4 8 group 1 vs 2 nn p 10 10 0.971 10 10 0.739 10 10 0.393 10 10 0.684 group 2 vs 4 nn p 10 10 0.912 10 10 <0.001 10 10 <0.001 10 10 <0.001 group 3 vs 7 nn p 10 10 1.000 10 10 <0.001 10 10 0.123 10 10 1.000 group 1 vs 3 nn p 10 10 0.971 10 10 0.631 10 10 0.089 10 10 0.043 group 2 vs 5 nn p 10 10 0.796 10 10 <0.001 10 9 <0.001 10 10 0.218 group 4 vs 5 nn p 10 10 1.000 10 10 0.029 10 9 0.400 10 10 <0.001 Plasma triglycerides, p values Mann-Whitney U-test group 1 vs 4 group 1 vs 5 group 1 vs 6 group 1 vs 7 nn p nn E nn p nn p 10 10 0.912 10 10 0.796 10 10 0.912 10 10 0.912 10 10 <0.001 10 10 <0.001 10 10 0.739 10 10 <0.001 10 10 <0.001 10 9 <0.001 10 10 <0.001 10 10 0.912 10 10 <0.001 10 10 0.353 10 10 0.002 10 10 0.007 group 2 vs 6 group 2 vs 7 group 3 vs 4 group 3 vs 5 nn p nn p nn p nn p 10 10 0.853 10 10 0.971 10 10 0.971 10 10 0.912 10 10 0.853 10 10 <0.001 10 10 0.002 10 10 <0.001 10 10 <0.001 10 10 0.529 10 10 0.063 10 9 0.017 10 10 0.003 10 10 0.029 10 10 0.001 10 10 0.529 group 4 vs 6 group 4 vs 7 group 5 vs 6 group 5 vs 7 nn p nn p nn p nn p 10 10 0.971 10 10 0.853 10 10 0.971 10 10 0.796 10 10 0.001 10 10 0.143 10 10 <0.001 10 10 0.190 10 10 0.143 10 10 0.001 9 10 0.133 9 10 0.001 10 10 0.004 10 10 <0.001 10 10 0.123 10 10 0.315 group 2 vs 3 nn p 10 10 0.971 10 10 0.393 10 10 0.023 10 10 0.029 group 3 vs 6 nn p 10 10 0.971 10 10 0.529 10 10 0.971 10 10 0.123 group 6 vs 7 nn p 10 10 0.796 10 10 0.190 10 10 0.001 10 10 0.315 p<0.05 Page A16 of A172 Appendix to TNO-report of 3M-02 Final version C3. Pooled lipoprotein profile measurements 04-12-2006 Week 0 C h olesterol fra ctio n 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 m easured c h o le s te ro l (m M ) po o le d s a m p le 1 0 .0 0 8 0 .0 0 2 0.021 0 .0 4 3 0 .2 9 2 0 .2 9 5 0 .1 6 6 0 .1 0 9 0 .0 8 7 0 .1 0 9 0 .1 1 5 0 .1 4 7 0 .2 2 2 0 .2 6 6 0 .2 5 7 0 .2 1 6 0 .2 3 2 0 .2 9 5 0 .3 0 7 0 .2 2 9 0 .1 4 7 0 .0 9 3 0.071 0 .0 4 0 dilu tio n c h o le s te ro l (m M ) 2 0.016 2 0.004 2 0.042 2 0.086 2 0.584 2 0.590 2 0.332 2 0.218 2 0.174 2 0.218 2 0.230 2 0.294 2 0.444 2 0.532 2 0.514 2 0.432 2 0.464 2 0.590 2 0.614 2 0.458 2 0.294 2 0.186 2 0.142 2 0.080 m easured c h o le ste ro l (m M ) po o le d s a m p le 2 0 .0 1 2 0 .0 0 8 0 .0 1 2 0 .0 6 8 0 .2 4 8 0 .2 3 5 0.131 0 .0 9 3 0 .0 7 5 0 .0 7 8 0 .1 0 0 0 .1 3 4 0 .1 8 8 0 .2 2 2 0 .2 2 9 0 .1 9 4 0 .2 1 0 0 .2 8 8 0 .2 8 8 0 .2 0 3 0 .1 2 2 0 .0 9 0 0 .0 4 9 0 .0 4 0 dilution c h o le s te ro l (m M ) 2 0.024 2 0.016 2 0.024 2 0.136 2 0.496 2 0.470 2 0.262 2 0.186 2 0.150 2 0.156 2 0.200 2 0.268 2 0.376 2 0.444 2 0.458 2 0.388 2 0.420 2 0.576 2 0.576 2 0.406 2 0.244 2 0.180 2 0.098 2 0.080 m easured c h o le ste ro l (m M ) p o o le d s a m p le 3 0 .0 1 2 0 .0 1 5 0 .0 0 5 0 .0 6 2 0 .2 7 0 0 .2 8 5 0 .1 6 3 0 .1 4 4 0 .1 0 3 0 .1 0 3 0 .1 3 4 0.181 0 .2 8 2 0 .3 1 4 0 .2 7 9 0.241 0 .2 3 8 0 .3 3 9 0 .3 7 0 0 .2 7 0 0 .1 6 6 0 .0 9 3 0 .0 5 9 0 .0 4 0 dilu tio n c h o le s te ro l (m M ) 2 0.024 2 0.030 2 0.010 2 0.124 2 0.540 2 0.570 2 0.326 2 0.288 2 0.206 2 0.206 2 0.268 2 0.362 2 0.564 2 0.628 2 0.558 2 0.482 2 0.476 2 0.678 2 0.740 2 0.540 2 0.332 2 0.186 2 0.118 2 0.080 A v e ra g e p lasm a cho le ste ro l (m m ol/l) 0.021 0 .0 1 7 0 .0 2 5 0 .1 1 5 0 .5 4 0 0 .5 4 3 0 .3 0 7 0.231 0 .1 7 7 0 .1 9 3 0 .2 3 3 0 .3 0 8 0.461 0 .5 3 5 0 .5 1 0 0 .4 3 4 0 .4 5 3 0 .6 1 5 0 .6 4 3 0 .4 6 8 0 .2 9 0 0 .1 8 4 0 .1 1 9 0 .0 8 0 sd 0 .0 0 5 0 .0 1 3 0 .0 1 6 0 .0 2 6 0 .0 4 4 0 .0 6 4 0 .0 3 9 0 .0 5 2 0 .0 2 8 0 .0 3 3 0 .0 3 4 0 .0 4 9 0 .0 9 5 0 .0 9 2 0 .0 5 0 0 .0 4 7 0 .0 2 9 0 .0 5 5 0 .0 8 6 0 .0 6 8 0 .0 4 4 0 .0 0 3 0 .0 2 2 0 .0 0 0 PL fra ctio n 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 m easured P L (m g/dl) po o le d s a m p le 1 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 3 .7 7 6 4 .4 2 9 2 .3 0 5 1 .7 0 6 1 .5 9 7 1 .6 5 2 1 .9 7 8 3 .5 0 3 5 .0 8 3 8 .6 2 3 7 .7 5 2 7.261 9 .0 5 9 1 2 .7 6 2 1 5 .1 0 4 1 2 .4 3 6 1 0 .0 9 4 5 .9 5 4 3 .9 3 9 1 .7 6 0 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 PL (m M ) 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 5 8 0 .0 6 8 0 .0 3 6 0 .0 2 6 0 .0 2 5 0 .0 2 6 0.031 0 .0 5 4 0 .0 7 9 0 .1 3 3 0 .1 2 0 0 .1 1 2 0 .1 4 0 0 .1 9 7 0 .2 3 4 0 .1 9 2 0 .1 5 6 0 .0 9 2 0.061 0 .0 2 7 m easured P L (m g/dl) po o le d sa m p le 2 0 .0 0 0 0 .0 0 0 0 .0 0 3 0 .9 8 4 3 .5 1 3 4 .2 3 5 2 .5 8 4 2 .0 1 6 1 .7 0 6 1.861 2 .0 1 6 3 .4 0 9 5 .7 3 2 7 .0 2 2 8 .4 1 6 7 .4 3 5 8 .6 2 2 1 5 .2 2 9 1 5 .1 7 7 13.061 9 .9 1 3 7 .7 0 4 3 .8 2 2 2.171 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 PL (m M ) 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 1 5 0 .0 5 4 0 .0 6 5 0 .0 4 0 0.031 0 .0 2 6 0 .0 2 9 0.031 0 .0 5 3 0 .0 8 9 0 .1 0 9 0 .1 3 0 0 .1 1 5 0 .1 3 3 0 .2 3 5 0 .2 3 5 0 .2 0 2 0 .1 5 3 0 .1 1 9 0 .0 5 9 0 .0 3 4 m easured PL (m g/dl) p o o le d s a m p le 3 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 4 .1 4 5 4 .1 9 9 2 .6 7 0 1 .8 5 0 1 .4 6 8 1 .7 9 6 2.561 3 .7 0 8 7 .3 1 3 9 .3 8 9 1 0 .0 4 4 8 .4 6 0 1 0 .0 9 9 1 7 .0 3 6 1 9 .1 6 7 1 5 .9 4 4 1 0 .9 1 8 7 .9 6 9 4 .4 1 8 1 .6 3 2 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 PL (m M ) 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 6 4 0 .0 6 5 0.041 0 .0 2 9 0 .0 2 3 0 .0 2 8 0 .0 4 0 0 .0 5 7 0 .1 1 3 0 .1 4 5 0 .1 5 5 0.131 0 .1 5 6 0 .2 6 3 0 .2 9 6 0 .2 4 6 0 .1 6 9 0 .1 2 3 0 .0 6 8 0 .0 2 5 A v e ra g e p la s m a P L(m M ) sd 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 5 0 .0 5 9 0 .0 6 6 0 .0 3 9 0 .0 2 9 0 .0 2 5 0 .0 2 7 0 .0 3 4 0 .0 5 5 0 .0 9 3 0 .1 2 9 0 .1 3 5 0 .1 1 9 0 .1 4 3 0 .2 3 2 0 .2 5 5 0 .2 1 4 0 .1 5 9 0.111 0 .0 6 3 0 .0 2 9 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 9 0 .0 0 5 0 .0 0 2 0 .0 0 3 0 .0 0 2 0 .0 0 2 0 .0 0 2 0 .0 0 5 0 .0 0 2 0 .0 1 8 0 .0 1 9 0 .0 1 8 0 .0 1 0 0 .0 1 2 0 .0 3 3 0 .0 3 6 0 .0 2 9 0 .0 0 8 0 .0 1 7 0 .0 0 5 0 .0 0 4 Page A17 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 week 4 C h olesterol fractio n 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 m easured cholestero l (mM ) pool group 1 0 .0 0 6 0 .0 0 6 0 .0 0 6 0 .0 2 8 0 .1 3 6 0 .1 3 9 0 .0 9 6 0 .0 7 4 0.071 0 .0 8 3 0 .1 2 6 0 .1 9 7 0 .2 7 2 0 .2 8 4 0.241 0 .2 0 4 0 .2 7 8 0 .4 4 2 0 .4 2 9 0 .2 6 5 0.151 0 .0 9 9 0 .0 6 5 0 .0 4 0 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A verage cholesterol (m M ) group 1 0 .0 1 2 0 .0 1 2 0 .0 1 2 0 .0 5 6 0 .2 7 2 0 .2 7 8 0 .1 9 2 0 .1 4 8 0 .1 4 2 0 .1 6 6 0 .2 5 2 0 .3 9 4 0 .5 4 4 0 .5 6 8 0 .4 8 2 0 .4 0 8 0 .5 5 6 0 .8 8 4 0 .8 5 8 0 .5 3 0 0 .3 0 2 0 .1 9 8 0 .1 3 0 0 .0 8 0 m easured cholestero l (m M ) pool group 2 0 .0 1 2 0 .0 0 9 0 .0 0 9 0 .0 6 2 0 .1 8 5 0 .1 5 7 0 .0 9 9 0 .0 7 4 0.071 0 .0 7 7 0 .1 2 0 0 .1 7 3 0 .2 2 5 0.231 0 .2 1 9 0 .2 0 7 0 .2 5 3 0 .3 5 8 0 .3 2 7 0 .2 0 4 0 .1 2 3 0 .0 8 0 0 .0 4 9 0 .0 3 4 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A verage cholestero l (m M ) group 2 0 .0 2 4 0 .0 1 8 0 .0 1 8 0 .1 2 4 0 .3 7 0 0 .3 1 4 0 .1 9 8 0 .1 4 8 0 .1 4 2 0 .1 5 4 0 .2 4 0 0 .3 4 6 0 .4 5 0 0 .4 6 2 0 .4 3 8 0 .4 1 4 0 .5 0 6 0 .7 1 6 0 .6 5 4 0 .4 0 8 0 .2 4 6 0 .1 6 0 0 .0 9 8 0 .0 6 8 m easured cholestero l (m M ) pool group 3 0 .0 0 9 0 .0 1 2 0 .0 0 9 0.031 0 .1 0 8 0 .1 4 2 0 .0 8 9 0 .0 7 7 0 .0 6 8 0 .0 8 3 0 .1 0 8 0 .1 5 7 0 .2 0 4 0 .2 0 7 0 .1 8 2 0 .1 7 9 0 .2 2 2 0 .3 3 7 0 .3 5 2 0 .2 3 8 0 .1 3 6 0 .0 8 6 0 .0 4 9 0.031 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A verage cholesterol (m M ) group 3 0 .0 1 8 0 .0 2 4 0 .0 1 8 0 .0 6 2 0 .2 1 6 0 .2 8 4 0 .1 7 8 0 .1 5 4 0 .1 3 6 0 .1 6 6 0 .2 1 6 0 .3 1 4 0 .4 0 8 0 .4 1 4 0 .3 6 4 0 .3 5 8 0 .4 4 4 0 .6 7 4 0 .7 0 4 0 .4 7 6 0 .2 7 2 0 .1 7 2 0 .0 9 8 0 .0 6 2 fra c tio n 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 m easured cholesterol (m M ) pool group 4 0.020 0.014 0.027 0.030 0.064 0.058 0.048 0.030 0.027 0.030 0.054 0.107 0.215 0.324 0.324 0.271 0.231 0.203 0.160 0.107 0.064 0.045 0.036 0.024 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average cholesterol (m M ) group 4 0.040 0.028 0.054 0.060 0.128 0.116 0.096 0.060 0.054 0.060 0.108 0.214 0.430 0.648 0.648 0.542 0.462 0.406 0.320 0.214 0.128 0.090 0.072 0.048 m easured cholesterol (m M ) pool group 5 0.008 0.008 0.005 0.024 0.076 0.079 0.051 0.036 0.033 0.030 0.030 0.061 0.132 0.209 0.259 0.231 0.209 0.209 0.175 0.116 0.073 0.039 0.036 0.017 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average cholesterol (m M ) group 5 0.016 0.016 0.010 0.048 0.152 0.158 0.102 0.072 0.066 0.060 0.060 0.122 0.264 0.418 0.518 0.462 0.418 0.418 0.350 0.232 0.146 0.078 0.072 0.034 m easured cholesterol (m M ) pool group 6 0.011 0.008 0.011 0.024 0.054 0.073 0.039 0.036 0.027 0.030 0.036 0.064 0.135 0.215 0.249 0.218 0.197 0.184 0.160 0.110 0.064 0.039 0.027 0.014 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A ve ra g e cholesterol (m M ) group 6 0.022 0.016 0.022 0.048 0.108 0.146 0.078 0.072 0.054 0.060 0.072 0.128 0.270 0.430 0.498 0.436 0.394 0.368 0.320 0.220 0.128 0.078 0.054 0.028 m easured cholesterol (m M ) pool group 7 0.016 0.013 0.010 0.025 0.120 0.126 0.065 0.049 0.031 0.034 0.043 0.095 0.246 0.436 0.525 0.458 0.359 0.277 0.203 0.129 0.083 0.049 0.040 0.025 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A v e ra g e cholesterol (m M ) group 7 0.032 0.026 0.020 0.050 0.240 0.252 0.130 0.098 0.062 0.068 0.086 0.190 0.492 0.872 1.050 0.916 0.718 0.554 0.406 0.258 0.166 0.098 0.080 0.050 Page A18 of A172 Appendix to TNO-report of 3M-02 Final version PL fractio n 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 m easured P L (m g/dl) pool group 1 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .1 1 3 0 .2 4 7 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .9 1 8 3.201 5 .7 5 2 7 .0 9 5 6 .2 8 9 6 .1 5 5 12.063 2 2 .8 0 4 2 3 .7 4 4 14.748 8 .3 0 3 4 .9 4 6 2.261 0 .2 4 7 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A verage PL (mM ) group 1 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 2 0 .0 0 4 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 1 4 0 .0 4 9 0 .0 8 9 0 .1 1 0 0 .0 9 7 0 .0 9 5 0 .1 8 6 0 .3 5 3 0 .3 6 7 0 .2 2 8 0 .1 2 8 0 .0 7 6 0 .0 3 5 0 .0 0 4 m easured P L(m g/dl) pool group 2 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 1.321 1.187 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .6 5 0 2 .6 6 4 4 .2 7 5 5 .8 8 6 5 .6 1 8 5 .8 8 6 10.317 17.702 17.433 10.586 5 .7 5 2 3 .8 7 2 1.187 0 .0 0 0 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A verage PL (m M ) group 2 0.000 0.000 0.000 0.000 0.020 0.018 0.000 0.000 0.000 0.000 0.010 0.041 0.066 0.091 0 .0 8 7 0.091 0.160 0.274 0.270 0.164 0.089 0.060 0.018 0.000 04-12-2006 m easured P L (m g/dl) pool group 3 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .5 1 6 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 0.381 1.992 3 .6 0 4 4.141 4 .4 0 9 4 .6 7 8 8 .8 4 0 17.031 19.448 12.331 7 .3 6 3 4 .8 1 2 1.321 0 .0 0 0 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A verage PL (mM ) group 3 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 8 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 6 0.031 0 .0 5 6 0 .0 6 4 0 .0 6 8 0 .0 7 2 0 .1 3 7 0 .2 6 3 0.301 0.191 0 .1 1 4 0 .0 7 4 0 .0 2 0 0 .0 0 0 fraction 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 m easured PL(m g/dl) pool group 4 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.939 4.149 8.162 9.232 8.162 6.557 6.825 5.487 2.946 1.340 0.939 0.000 0.000 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average PL (m M ) group 4 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.015 0.064 0.126 0.143 0.126 0.101 0.106 0.085 0.046 0.021 0.015 0.000 0.000 m easured PL(m g/dl) pool group 5 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 1.742 4 .5 5 1 6.825 6.825 6.022 7.226 6.022 3 .4 8 1 1.875 0.672 0.000 0.000 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average PL (m M ) group 5 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.027 0.070 0.106 0.106 0.093 0.112 0.093 0.054 0.029 0.010 0.000 0.000 m easured PL(m g/dl) pool group 6 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 1.742 4.283 6.022 5 .6 2 1 5.219 5.487 5.086 2.812 1.207 0.538 0.000 0.000 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average PL (m M ) group 6 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.027 0.066 0.093 0.087 0.081 0.085 0.079 0.043 0.019 0.008 0.000 0.000 m easured PL(m g/dl) pool group 7 0.000 0.000 0.000 0.000 0.000 0.187 0.000 0.000 0.000 0.000 0.000 0.858 5.690 11.998 16.024 15.085 12.400 10.253 7.435 4.348 2.603 1.529 0 .3 2 1 0.000 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average PL (m M ) group 7 0.000 0.000 0.000 0.000 0.000 0.003 0.000 0.000 0.000 0.000 0.000 0.013 0.088 0.185 0.248 0.233 0.192 0.159 0.115 0.067 0.040 0.024 0.005 0.000 Page A19 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Week 6 C h oleste rol fractio n 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 m easured cholesterol (mM) pool group 1 0 .0 1 0 0.001 0 .0 0 4 0 .0 2 5 0 .1 3 5 0 .1 3 5 0 .0 8 3 0 .0 6 5 0 .0 5 6 0 .0 7 4 0 .1 2 9 0 .2 2 3 0 .2 9 3 0 .2 9 3 0 .2 3 8 0 .1 8 3 0.241 0 .3 6 8 0 .3 4 7 0 .2 2 0 0 .1 3 2 0 .0 9 2 0 .0 6 2 0 .0 4 4 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A verage cholestero l (m M ) group 1 0 .0 2 0 0 .0 0 2 0 .0 0 8 0 .0 5 0 0 .2 7 0 0 .2 7 0 0 .1 6 6 0 .1 3 0 0 .1 1 2 0 .1 4 8 0 .2 5 8 0 .4 4 6 0 .5 8 6 0 .5 8 6 0 .4 7 6 0 .3 6 6 0 .4 8 2 0 .7 3 6 0 .6 9 4 0 .4 4 0 0 .2 6 4 0 .1 8 4 0 .1 2 4 0 .0 8 8 m easured cholestero l (m M ) pool group 2 0 .0 0 7 0 .0 0 7 0.004 0.050 0.174 0 .1 4 7 0.083 0.065 0.050 0.068 0.114 0.186 0.226 0.211 0.180 0 .1 6 2 0.220 0.274 0.241 0.153 0.086 0.059 0.035 0 .0 2 2 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A verage cholestero l (m M ) group 2 0 .0 1 4 0 .0 1 4 0 .0 0 8 0 .1 0 0 0 .3 4 8 0 .2 9 4 0 .1 6 6 0 .1 3 0 0 .1 0 0 0 .1 3 6 0 .2 2 8 0 .3 7 2 0 .4 5 2 0 .4 2 2 0 .3 6 0 0 .3 2 4 0 .4 4 0 0 .5 4 8 0 .4 8 2 0 .3 0 6 0 .1 7 2 0 .1 1 8 0 .0 7 0 0 .0 4 4 m easured cholesterol (m M ) pool group 3 0 .0 1 3 0 .0 1 3 0 .0 1 0 0 .0 6 2 0 .1 8 9 0 .1 6 8 0 .0 9 2 0 .0 7 7 0 .0 6 2 0 .0 8 3 0 .1 2 3 0 .1 8 0 0 .2 2 3 0.211 0 .1 6 2 0 .1 5 6 0 .2 3 5 0 .3 2 9 0 .2 9 6 0 .1 8 9 0 .1 1 4 0 .0 7 4 0 .0 4 7 0 .0 3 2 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A verage cholestero l (m M ) group 3 0 .0 2 6 0 .0 2 6 0 .0 2 0 0 .1 2 4 0 .3 7 8 0 .3 3 6 0 .1 8 4 0 .1 5 4 0 .1 2 4 0 .1 6 6 0 .2 4 6 0 .3 6 0 0 .4 4 6 0 .4 2 2 0 .3 2 4 0 .3 1 2 0 .4 7 0 0 .6 5 8 0 .5 9 2 0 .3 7 8 0 .2 2 8 0 .1 4 8 0 .0 9 4 0 .0 6 4 fraction 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 m easured cholesterol (m M ) pool group 4 0.016 0.004 0.010 0.022 0.068 0.056 0.034 0.031 0.025 0.028 0.059 0.138 0.251 0.315 0.300 0.217 0.168 0.129 0.080 0.056 0.037 0.028 0.025 0.019 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average cholesterol (m M ) group 4 0.032 0.008 0.020 0.044 0.136 0.112 0.068 0.062 0.050 0.056 0.118 0.276 0.502 0.630 0.600 0.434 0.336 0.258 0.160 0.112 0.074 0.056 0.050 0.038 m easured cholesterol (m M ) dilution pool group 5 0.010 2 0.004 2 0.010 2 0.077 2 0.248 2 0.193 2 0.117 2 0.080 2 0 .0 7 1 2 0.077 2 0.129 2 0.220 2 0 .2 8 1 2 0 .2 5 1 2 0.202 2 0.156 2 0.205 2 0 .2 8 1 2 0.254 2 0.150 2 0.092 2 0.056 2 0.043 2 0.037 2 Average cholesterol (m M ) group 5 0.020 0.008 0.020 0.154 0.496 0.386 0.234 0.160 0.142 0.154 0.258 0.440 0.562 0.502 0.404 0.312 0.410 0.562 0.508 0.300 0.184 0.112 0.086 0.074 m easured cholesterol (m M ) pool group 6 0.016 0.025 0.016 0.037 0.071 0.071 0.037 0.034 0.031 0.037 0.053 0.120 0.214 0.266 0.266 0.211 0.156 0.126 0.080 0.049 0.037 0.025 0.016 0.013 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average cholesterol (m M ) group 6 0.032 0.050 0.032 0.074 0.142 0.142 0.074 0.068 0.062 0.074 0.106 0.240 0.428 0.532 0.532 0.422 0.312 0.252 0.160 0.098 0.074 0.050 0.032 0.026 m easured cholesterol (m M ) pool group 7 0.008 0.011 0.011 0.029 0.093 0.081 0.051 0.045 0.036 0.045 0.075 0.142 0.306 0.425 0.407 0.306 0.206 0.139 0.081 0.054 0.039 0.033 0.026 0.017 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average cholesterol (m M ) group 7 0.016 0.022 0.022 0.058 0.186 0.162 0.102 0.090 0.072 0.090 0.150 0.284 0.612 0.850 0.814 0.612 0.412 0.278 0.162 0.108 0.078 0.066 0.052 0.034 Page A20 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 PL fraction 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 measured PL(mg/dl) pool group1 0.000 0.000 0.000 0.000 1.035 1.166 0.246 0.115 0.115 1.035 2.349 4.977 6.948 7.605 6.685 6.685 11.415 19.168 18.248 11.678 7.342 4.977 2.086 0.772 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average PL(mM) group1 0.000 0.000 0.000 0.000 0.016 0.018 0.004 0.002 0.002 0.016 0.036 0.077 0.107 0.118 0.103 0.103 0.176 0.296 0.282 0.181 0.114 0.077 0.032 0.012 measured PL(mg/dl) pool group2 0.000 0.000 0.000 0.000 1.823 1.297 0.903 0.640 0.246 0.509 1.823 4.057 5.502 6.159 5.897 6.028 9.313 13.649 12.729 8.525 4.714 2.874 1.035 0.115 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average PL(mM) group2 0.000 0.000 0.000 0.000 0.028 0.020 0.014 0.010 0.004 0.008 0.028 0.063 0.085 0.095 0.091 0.093 0.144 0.211 0.197 0.132 0.073 0.044 0.016 0.002 measured PL(mg/dl) pool group3 0.000 0.000 0.000 0.000 1.429 1.429 0.115 0.115 0.000 0.640 2.743 3.400 4.451 4.845 4.188 5.108 9.050 14.963 14.306 9.182 5.239 3.268 1.035 0.246 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average PL(mM) group3 0.000 0.000 0.000 0.000 0.022 0.022 0.002 0.002 0.000 0.010 0.042 0.053 0.069 0.075 0.065 0.079 0.140 0.231 0.221 0.142 0.081 0.051 0.016 0.004 fra c tio n 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 m easured PL(m g/dl) pool group 4 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.505 2.599 6.264 9.405 9.798 7.835 5.872 4.301 2.861 1.683 1.291 0.636 0.000 0.000 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average PL (mM) group 4 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.008 0.040 0.097 0.145 0.151 0.121 0.091 0.066 0.044 0.026 0.020 0.010 0.000 0.000 m easured PL(m g/dl) pool group 5 0.000 0.000 0.000 0.113 2.338 1.945 0.898 0.505 0.505 0.898 2.730 5.479 7.442 7.442 6.133 6.002 8.489 12.808 12.547 8.227 5.217 2.992 1.160 0.243 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A verage PL (m M ) group 5 0.000 0.000 0.000 0.002 0.036 0.030 0.014 0.008 0.008 0.014 0.042 0.085 0.115 0.115 0.095 0.093 0.131 0.198 0.194 0.127 0.081 0.046 0.018 0.004 m easured PL(m g/dl) pool group 6 0.000 0.000 0.000 0.000 0.000 0.505 0.000 0.000 0.000 0.000 0.374 2.338 5.348 7.966 8.882 7.049 5.610 4.039 2.599 1.552 0.898 0.505 0.000 0.000 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average PL (m M ) group 6 0.000 0.000 0.000 0.000 0.000 0.008 0.000 0.000 0.000 0.000 0.006 0.036 0.083 0.123 0.137 0.109 0.087 0.062 0.040 0.024 0.014 0.008 0.000 0.000 m easured PL(m g/dl) pool group 7 0.000 0.000 0.000 0.000 0.282 0.414 0.000 0.000 0.000 0.017 0.678 3.583 8.866 13.621 14.413 11.508 7.281 4.640 2.131 1.074 0.678 0.414 0.000 0.000 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average PL (m M ) group 7 0.000 0.000 0.000 0.000 0.004 0.006 0.000 0.000 0.000 0.000 0.010 0.055 0.137 0.211 0.223 0.178 0.113 0.072 0.033 0.017 0.010 0.006 0.000 0.000 Page A21 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Week 8 C h olesterol fractio n 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 m easured cholestero l (mM ) pool group 1 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 3 6 0.191 0 .1 6 7 0 .1 0 3 0 .0 7 8 0 .0 7 8 0 .1 0 0 0 .1 6 4 0 .2 6 7 0 .3 2 8 0 .2 9 2 0 .2 4 0 0.191 0 .2 4 9 0 .3 4 6 0 .3 4 6 0 .2 0 0 0 .1 0 9 0 .0 6 6 0 .0 4 8 0 .0 2 7 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A verage cholestero l (m M ) group 1 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 7 2 0 .3 8 2 0 .3 3 4 0 .2 0 6 0 .1 5 6 0 .1 5 6 0 .2 0 0 0 .3 2 8 0 .5 3 4 0 .6 5 6 0 .5 8 4 0 .4 8 0 0 .3 8 2 0 .4 9 8 0 .6 9 2 0 .6 9 2 0 .4 0 0 0 .2 1 8 0 .1 3 2 0 .0 9 6 0 .0 5 4 m easured cholestero l (m M ) pool group 2 0 .0 0 0 0 .0 0 0 0 .0 0 2 0 .0 6 6 0 .2 2 8 0 .1 8 2 0 .1 0 9 0 .0 7 8 0 .0 6 9 0 .0 8 7 0 .1 3 9 0 .2 0 0 0 .2 4 9 0 .2 5 2 0 .2 3 7 0 .1 9 7 0 .2 3 7 0 .2 7 6 0 .2 4 0 0 .1 3 6 0 .0 7 8 0.051 0 .0 2 3 0 .0 2 0 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A verage cholestero l (m M ) group 2 0.000 0.000 0.004 0 .1 3 2 0.456 0.364 0.218 0.156 0.138 0.174 0.278 0.400 0.498 0.504 0.474 0.394 0.474 0 .5 5 2 0.480 0 .2 7 2 0.156 0 .1 0 2 0.046 0.040 m easured cholestero l (m M ) pool group 3 0 .0 0 0 0.011 0.011 0 .0 5 4 0 .2 0 6 0 .1 7 9 0 .1 1 2 0.091 0 .0 7 5 0 .1 1 2 0 .1 6 4 0 .2 4 6 0 .2 9 8 0 .2 7 3 0 .2 3 7 0 .1 8 8 0.231 0 .3 1 0 0 .2 8 8 0 .1 7 0 0 .0 9 7 0 .0 6 3 0 .0 3 0 0 .0 2 0 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A verage cholestero l (m M ) group 3 0 .0 0 0 0 .0 2 2 0 .0 2 2 0 .1 0 8 0 .4 1 2 0 .3 5 8 0 .2 2 4 0 .1 8 2 0 .1 5 0 0 .2 2 4 0 .3 2 8 0 .4 9 2 0 .5 9 6 0 .5 4 6 0 .4 7 4 0 .3 7 6 0 .4 6 2 0 .6 2 0 0 .5 7 6 0 .3 4 0 0 .1 9 4 0 .1 2 6 0 .0 6 0 0 .0 4 0 fraction 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 m easured cholesterol (m M ) pool group 4 0.015 0.000 0.006 0.021 0.061 0.052 0.023 0.021 0.012 0.035 0.044 0.118 0.271 0.357 0.363 0.280 0.205 0.162 0.107 0.067 0.044 0.023 0.018 0.015 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A ve ra g e cholesterol (m M ) group 4 0.030 0.001 0.012 0.042 0.122 0.104 0.046 0.042 0.024 0.070 0.088 0.236 0.542 0.714 0.726 0.560 0.410 0.324 0.214 0.134 0.088 0.046 0.036 0.030 m ea su re d cholesterol (m M ) pool group 5 0.000 0.000 0.006 0.041 0.153 0.130 0.078 0.058 0.049 0.058 0.098 0.159 0.210 0.225 0.208 0.179 0.199 0.257 0.222 0.144 0.075 0.052 0.029 0.029 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average cholesterol (m M ) group 5 0.000 0.000 0.012 0.082 0.306 0.260 0.156 0.116 0.098 0.116 0.196 0.318 0.420 0.450 0.416 0.358 0.398 0.514 0.444 0.288 0.150 0.104 0.058 0.058 m easured cholesterol (m M ) pool group 6 0.000 0.006 0.009 0.035 0.107 0.095 0.061 0.044 0.038 0.032 0.067 0.150 0.265 0.372 0.377 0.300 0.239 0.196 0.150 0.092 0.052 0.032 0.021 0.021 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A v e ra g e cholesterol (m M ) group 6 0.001 0.012 0.018 0.070 0.214 0.190 0.122 0.088 0.076 0.064 0.134 0.300 0.530 0.744 0.754 0.600 0.478 0.392 0.300 0.184 0.104 0.064 0.042 0.042 m easured cholesterol (m M ) pool group 7 0.000 0.000 0.003 0.041 0.167 0.135 0.073 0.056 0.038 0.050 0.079 0.170 0.302 0.419 0.419 0.328 0.246 0.199 0.138 0.085 0.053 0.035 0.023 0.011 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average cholesterol (m M ) group 7 0.000 0.000 0.006 0.082 0.334 0.270 0.146 0.112 0.076 0.100 0.158 0.340 0.604 0.838 0.838 0.656 0.492 0.398 0.276 0.170 0.106 0.070 0.046 0.022 Page A22 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 EL fractio n 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 m easured P L (m g/dl) pool group 1 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 2 .0 6 7 1.800 0.601 0.201 0 .3 3 4 1.400 3 .2 6 6 6 .5 9 9 8 .9 9 8 8 .7 3 2 7 .1 3 2 7 .2 6 5 11.931 2 0 .5 9 5 18.596 11.531 7 .2 6 5 4 .7 3 3 2 .4 6 7 0 .8 6 7 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A verage PL (mM ) group 1 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 3 2 0 .0 2 8 0 .0 0 9 0 .0 0 3 0 .0 0 5 0 .0 2 2 0 .0 5 0 0 .1 0 2 0 .1 3 9 0 .1 3 5 0 .1 1 0 0 .1 1 2 0 .1 8 4 0 .3 1 8 0 .2 8 7 0 .1 7 8 0 .1 1 2 0 .0 7 3 0 .0 3 8 0 .0 1 3 m easured P L (m g/dl) pool group 2 0 .0 0 0 0 .0 0 0 0 .0 0 0 0.201 3 .0 0 0 2 .0 6 7 0 .8 6 7 0.201 0 .3 3 4 1.000 2 .6 0 0 4 .9 9 9 6 .8 6 6 7 .9 3 2 7 .6 6 5 8 .0 6 5 10.731 15.130 12.864 8 .0 6 5 5 .2 6 6 3 .2 6 6 1.000 0 .0 0 0 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A verage PL (mM ) group 2 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 3 0 .0 4 6 0 .0 3 2 0 .0 1 3 0 .0 0 3 0 .0 0 5 0 .0 1 5 0 .0 4 0 0 .0 7 7 0 .1 0 6 0 .1 2 3 0 .1 1 9 0 .1 2 5 0 .1 6 6 0 .2 3 4 0 .1 9 9 0 .1 2 5 0.081 0 .0 5 0 0 .0 1 5 0 .0 0 0 m easured P L(m g/dl) pool group 3 0 .0 0 0 0 .0 0 0 0 .0 0 0 0 .0 0 0 2 .2 0 0 2 .0 6 7 0 .8 6 7 0 .3 3 4 0 .7 3 4 1.400 3 .5 3 3 6 .1 9 9 8 .1 9 9 8 .7 3 2 7 .2 6 5 7 .3 9 9 10.864 17.929 15.930 9 .7 9 8 6 .7 3 2 4 .2 0 0 1.534 0 .3 3 4 d ilu tio n 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 A verage PL (mM ) group 3 0.000 0.000 0.000 0.000 0.034 0 .0 3 2 0.013 0.005 0.011 0 .0 2 2 0.055 0.096 0 .1 2 7 0.135 0 .1 1 2 0.114 0.168 0 .2 7 7 0.246 0.151 0.104 0.065 0.024 0.005 fraction 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 m ea su re d PL(m g/dl) pool group 4 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.048 2.583 8.185 12.587 12.987 10.453 8.052 6.184 4.183 2.583 1.916 1.115 0.000 0.000 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average PL (m M ) group 4 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.001 0.040 0.127 0.195 0.201 0.162 0.124 0.096 0.065 0.040 0.030 0.017 0.000 0.000 m ea su re d PL(m g/dl) pool group 5 0.000 0.000 0.000 0.000 1.515 1.249 0.181 0.000 0.000 0.448 1.515 3.916 5.517 6.851 6.851 7.118 9.786 14.454 13.521 8.318 4.450 3.116 0.848 0.315 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average PL (m M ) group 5 0.000 0.000 0.000 0.000 0.023 0.019 0.003 0.000 0.000 0.007 0.023 0.061 0.085 0.106 0.106 0.110 0.151 0.223 0.209 0.129 0.069 0.048 0.013 0.005 m easured PL(m g/dl) pool group 6 0.000 0.000 0.000 0.000 0.715 0.582 0.000 0.000 0.000 0.000 0.715 3.783 8.452 12.720 13.120 11.386 9.519 8.318 5.917 3.650 2.983 2.182 0.315 0.000 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average PL (m M ) group 6 0.000 0.000 0.000 0.000 0.011 0.009 0.000 0.000 0.000 0.000 0.011 0.058 0.131 0.197 0.203 0.176 0.147 0.129 0.091 0.056 0.046 0.034 0.005 0.000 m easured PL(m g/dl) pool group 7 0.000 0.000 0.000 0.000 1.619 0.951 0.150 0.000 0.000 0.000 0.951 4.290 10.033 13.639 14.707 12.570 10.166 8.163 5.626 3.622 2.687 1.619 0.150 0.000 dilution 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Average PL (m M ) group 7 0.000 0.000 0.000 0.000 0.025 0.015 0.002 0.000 0.000 0.000 0.015 0.066 0.155 0.211 0.227 0.194 0.157 0.126 0.087 0.056 0.042 0.025 0.002 0.000 Page A23 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 C4. Pooled plasma ALAT measurements group GGGGGGrrrrorrooooouuuuuuppGppppr647o523::::::uHHpHHHHFFFFFF1++:++++H000000F...0.0..000000c11233o6n%%%%%%troPPPPPPlFFFFFFOHBBOHSSSSSS Pooled plasma ALAT (U/l) week 0 mweeaesukr4ed dilution week 4 week 6 (o/n fast) 97.1 22381147380016....199756 3333333 289733161102536...778.3851 22311181401034367380 week 8 84331157579387.004402 Page A24 of A172 Appendix to TNO-report of 3M-02 Final version 0Q. 0Q. << C5. Plasma ketone bodies measurements Week -1 concentration ketonbodies (m m ol/l) 0 .0 0 0 0 .0 0 0 0.033 0.033 0.067 0.067 0.134 0.134 0.268 0.268 0.535 0.535 1 .0 7 0 1 .0 7 0 2.140 2.140 A 340 pre 0.214 0.214 0.218 0.215 0.218 0 .2 2 2 0.216 0.2 2 0.218 0.215 0.218 0.215 0.217 0.218 0.217 0.2 2 0 .2 1 1 0.214 0 .2 2 2 0.2 2 0.223 0.239 0.249 0.257 0.282 0.284 0.348 0.358 0.462 0.484 0.689 0.716 A 340 netto -0.003 0 0.004 0.005 0.005 0.017 0.033 0.037 0.064 0.069 0 .1 3 0.143 0.245 0.266 0.472 0.496 y=ax + b mouse# 641 645 646 650 652 655 656 657 658 663 665 666 667 670 671 674 678 679 680 681 686 687 690 696 699 700 704 705 706 710 712 714 716 720 721 724 727 729 730 731 737 738 740 741 742 744 748 752 754 756 758 759 760 761 762 763 765 766 768 769 771 774 776 778 782 783 784 785 790 791 792 793 795 797 799 a: | 0.2283 ~ | b: | 0.0028 A 340 pre 0.307 0.321 0.3 0.269 0.293 0.329 0.307 0.381 0.293 0 .3 5 0.245 0.276 0.273 0.351 0.324 0.464 0.291 0.447 0.334 0.468 0.352 0.467 0.356 0.274 0.3 0.305 0.311 0.294 0.292 0.419 0.388 0.289 0.333 0.346 0.302 0.347 0 .2 9 0.244 0.317 0 .2 7 0.432 0.387 0.351 0.249 0.239 0.242 0 .2 6 0.284 0.366 0.282 0.333 0.317 0.303 0.293 0.277 0.297 0.287 0.309 0.383 0.382 0.318 0.357 0.31 0.241 0.298 0.282 0.284 0.272 0.253 0.326 0.292 0.261 0.371 0.339 0 .30 1 0.766 0.546 0.623 0.644 0.546 0 .5 3 0.505 0 .6 7 0.658 0 .5 8 0.489 0 .6 5 0 .6 6 8 0.621 0.613 0.628 0.534 0.649 0.579 0.736 0.608 0.638 0.644 0.546 0.563 0.583 0 .6 6 6 0.609 0.621 0.664 0.624 0.573 0.465 0.692 0.705 0.754 0 .4 4 0 .3 7 0.423 0.405 0.712 0.581 0.578 0.485 0.418 0.516 0.429 0.445 0.631 0.558 0.664 0.613 0.605 0.639 0.623 0 .6 9 0 .6 2 0.627 0.632 0.693 0.533 0.554 0.521 0.466 0.596 0.556 0.653 0.645 0.452 0.589 0 .5 8 0.403 0.561 0.712 0 .57 2 A 340 netto 0.459 0.225 0.323 0.375 0.253 0 .2 0 1 0.198 0.289 0.365 0 .2 3 0.244 0.374 0.395 0 .2 7 0.289 0.164 0.243 0 .2 0 2 0.245 0.268 0.256 0.171 0.288 0.272 0.263 0.278 0.355 0.315 0.329 0.245 0.236 0.284 0.132 0.346 0.403 0.407 0 .1 5 0.126 0.106 0.135 0 .2 8 0.194 0.227 0.236 0.179 0.274 0.169 0.161 0.265 0.276 0.331 0.296 0.302 0.346 0.346 0.393 0.333 0.318 0.249 0.311 0.215 0.197 0 .2 1 1 0.225 0.298 0.274 0.369 0.373 0.199 0.263 0.288 0.142 0 .1 9 0.373 0.271 meas. concentration ketonbodies (m m ol/l) 2 .0 0 0.97 1 .4 0 1 .6 3 1.1 0 0.87 0 .8 6 1 .2 5 1 .5 9 1.0 0 1 .0 6 1 .6 3 1 .7 2 1 .1 7 1 .2 5 0.71 1 .0 5 0.87 1 .0 6 1 .1 6 1 .1 1 0.74 1 .2 5 1 .1 8 1 .1 4 1 .2 1 1 .5 4 1 .3 7 1 .4 3 1 .0 6 1.0 2 1 .2 3 0.57 1 .5 0 1 .7 5 1 .7 7 0.64 0.54 0.45 0.58 1 .2 1 0.84 0.98 1.0 2 0.77 1 .1 9 0.73 0.69 1 .1 5 1.2 0 1 .4 4 1 .2 8 1.31 1 .5 0 1 .5 0 1.71 1 .4 5 1 .3 8 1 .0 8 1 .3 5 0.93 0.85 0.91 0.97 1 .2 9 1 .1 9 1 .6 0 1 .6 2 0 .8 6 1 .1 4 1 .2 5 0.61 0.82 1 .6 2 1 .1 7 dilution 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 2 2 2 1 1 1 1 1 1 1 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 1 1 1 1 1 1 Plasma keton bodies (m mol/l) 2.0 0 0 .9 7 1.40 1.63 1 .1 0 0 .8 7 0.8 6 1.25 1.59 1 .0 0 1.06 1.63 1.72 1.17 1.25 0.71 1.05 0 .8 7 1.06 1.16 1.11 0 .7 4 1.25 1.18 1.14 1.21 1.54 1.37 1.43 1.06 1 .0 2 1.23 0 .5 7 1.50 1.75 1.77 1.29 1.08 0 .9 0 1.16 1.21 0 .8 4 0 .9 8 1 .0 2 0 .7 7 1.19 0 .7 3 1.39 1.15 1 .2 0 1.44 1.28 1.31 1.50 1.50 1.71 1.45 1.38 1.08 1.35 0 .9 3 0 .8 5 0.91 0 .9 7 1.29 1.19 1.60 1.62 1.72 1.14 1.25 0.61 0 .8 2 1.62 1.17 mouse# after matching 11 12 13 21 61 excluded excluded 62 1 2 41 42 43 63 44 14 22 45 64 31 32 65 23 66 24 46 33 34 35 36 3 51 4 67 52 68 53 25 47 48 15 16 17 excluded excluded 49 excluded 5 26 27 6 28 18 69 70 7 19 29 37 54 38 55 56 57 58 59 8 20 9 10 39 30 40 60 50 04-12-2006 Page A25 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Week 6 concentration odies (m mol/l) 0.000 0.000 0.033 0.033 0.067 0.067 0.134 0.134 0.268 0.268 0.535 0.535 1.070 1.070 2.140 2.140 A340 pre 0.255 0.254 0.255 0.258 0.256 0.262 0.257 0.262 0.257 0.256 0.258 0.257 0.256 0.261 0.259 0.266 A340 post 0.242 0.246 0.251 0.254 0.261 0.269 0.279 0.287 0.318 0.319 0.388 0.392 0.5 0.521 0.729 0.768 A340 netto -0 .0 1 3 -0 .0 0 8 -0 .0 0 4 -0 .0 0 4 0.005 0.007 0.022 0.025 0.061 0.063 0.13 0.135 0.244 0.26 0.47 0.502 Keton bodies (mmol/l) y=ax + b Group 1 1 1 1 1 AVERAGE SD 2 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 4 4 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 7 AVERAGE SD a: | 0.233 | Mouse# cage# 11 21 32 42 53 63 74 85 95 10 5 b: | -0.00531 eartag L 0 1 0 2 0 0 1 0 0 1 R 1 2 0 0 0 2 1 0 2 2 A340 pre 0.303 0.284 0.273 0.271 0.267 0.27 0.283 0.27 0.269 0.28 11 6 1 0 0.289 12 6 2 1 0.288 13 6 0 2 0.273 14 7 0 1 0.288 15 8 1 0 0.282 16 8 0 1 0.299 17 8 2 0 0.308 18 9 0 0 0.271 19 9 2 1 0.267 20 10 1 0 0.27 21 11 0 1 0.279 22 12 0 2 0.277 23 13 0 1 0.318 24 13 1 1 0.291 25 14 1 0 0.262 26 15 0 1 0.272 27 15 2 0 0.261 28 15 1 2 0.269 29 16 0 2 0.28 30 17 1 0 0.269 31 18 1 0 0.262 32 18 0 2 0.266 33 19 0 0 0.275 34 19 1 0 0.275 35 19 0 1 0.285 36 19 0 2 0.284 37 20 0 0 0.263 38 20 1 1 0.263 39 21 0 0 0.272 40 21 1 1 0.273 41 22 1 0 0.259 42 22 0 1 0.29 43 22 1 1 0.299 44 22 1 2 0.284 45 23 1 2 0.315 46 24 2 0 0.305 47 25 0 1 0.309 48 25 1 1 0.295 49 26 0 0 0.253 50 27 1 2 0.296 51 28 0 1 0.263 52 29 1 0 0.261 53 29 1 2 0.276 54 30 1 0 0.262 55 30 0 2 0.262 56 31 0 0 0.278 57 31 0 1 0.264 58 31 0 2 0.274 59 31 2 2 0.283 60 32 2 1 0.284 61 33 2 0 0.266 62 34 1 0 0.269 63 35 0 2 0.268 64 36 0 0 0.268 65 36 1 2 0.268 66 37 0 0 0.27 67 38 0 0 0.268 68 38 2 0 0.269 69 39 1 0 0.277 70 39 0 1 0.274 A340 post 0.443 0.402 0.383 0.359 0.382 0.363 0.424 0.38 0.367 0.379 0.413 0.343 0.382 0.468 0.395 0.347 0.364 0.413 0.366 0.383 0.443 0.473 0.409 0.38 0.421 0.418 0.419 0.374 0.445 0.372 0.409 0.381 0.424 0.439 0.452 0.446 0.417 0.365 0.49 0.427 0.435 0.437 0.541 0.408 0.558 0.529 0.399 0.439 0.44 0.466 0.581 0.556 0.541 0.54 0.551 0.605 0.408 0.605 0.564 0.659 0.551 0.568 0.566 0.522 0.541 0.579 0.615 0.568 0.618 0.647 A340 netto 0.14 0.118 0.11 0.088 0.115 0.093 0.141 0.11 0.098 0.099 0.124 0.055 0.109 0.18 0.113 0.048 0.056 0.142 0.099 0.113 0.164 0.196 0.091 0.089 0.159 0.146 0.158 0.105 0.165 0.103 0.147 0.115 0.149 0.164 0.167 0.162 0.154 0.102 0.218 0.154 0.176 0.147 0.242 0.124 0.243 0.224 0.09 0.144 0.187 0.17 0.318 0.295 0.265 0.278 0.289 0.327 0.144 0.331 0.281 0.375 0.285 0.299 0.298 0.254 0.273 0.309 0.347 0.299 0.341 0.373 meas. concentration ketonbodies (mmol/l) 0.62 0.53 0.49 0.40 0.52 0.42 0.63 0.49 0.44 0.45 0.55 0.26 0.49 0.80 0.51 0.23 0.26 0.63 0.45 0.51 0.73 0.86 0.41 0.40 0.71 0.65 0.70 0.47 0.73 0.46 0.65 0.52 0.66 0.73 0.74 0.72 0.68 0.46 0.96 0.68 0.78 0.65 1.06 0.55 1.07 0.98 0.41 0.64 0.83 0.75 1.39 1.29 1.16 1.22 1.26 1.43 0.64 1.44 1.23 1.63 1.25 1.31 1.30 1.11 1.19 1.35 1.51 1.31 1.49 1.62 dilution 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 Plasma keton bodies (mmol/l) 1.87 1.59 1.48 1.20 1.55 1.27 1.88 1.48 1.33 1.34 1.50 0.23 1.66 0.78 1.47 2.39 1.52 0.69 0.79 1.90 1.34 1.52 1.41 0.54 2.18 2.59 1.24 1.21 2.12 1.95 2.10 1.42 2.19 1.39 1.84 0.48 1.96 1.55 1.99 2.18 2.22 2.15 2.05 1.38 2.88 2.05 2.04 0.40 2.33 1.96 3.18 1.66 3.20 2.95 1.23 1.92 2.48 2.26 2.32 0.65 4.16 3.87 3.48 3.65 3.79 4.28 1.92 4.33 3.69 4.90 3.81 0.78 3.74 3.92 3.91 3.34 3.58 4.05 4.54 3.92 4.46 4.87 4.03 0.47 Page A26 of A172 Appendix to TNO-report of 3M-02 Final version G roup M ouse# cage# i i 1 1 1 1 1 1 1 1 AVERAGE SD 2 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 4 4 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 7 AVERAGE SD e x c lu d e d (655) e x c lu d e d (656) e x c lu d e d (741) e x c lu d e d (7 4 2 ) e x c lu d e d (748) i 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 1 1 2 2 3 3 4 5 5 5 6 6 6 7 8 8 8 9 9 10 11 12 13 13 14 15 15 15 16 17 18 18 19 19 19 19 20 20 21 21 22 22 22 22 23 24 25 25 26 27 28 29 29 30 30 31 31 31 31 32 33 34 35 36 36 37 38 38 39 39 earta g LR 01 12 00 20 00 02 11 00 02 12 10 21 02 01 10 01 20 00 21 10 01 02 01 11 10 01 20 12 02 10 10 02 00 10 01 02 00 11 00 11 10 01 11 12 12 20 01 11 00 12 01 10 12 10 02 00 01 02 22 21 20 10 02 00 12 00 00 20 10 01 1 P la sm a k e to n b o d ie s (m m o l/l) 1 w e e k -1 week 6 1.59 1.00 1.02 0 .5 7 1.39 1.44 1.71 1.60 1.72 1.14 1.87 1.59 1.48 1.20 1.55 1.27 1.88 1.48 1.33 1.34 1.32 0 .3 8 1.50 0 .2 3 2 .0 0 1.66 0 .9 7 1.40 0.71 1.21 0 .8 4 0 .9 8 1.31 1.45 1.62 0 .7 8 1.47 2 .3 9 1.52 0 .6 9 0 .7 9 1.90 1.34 1.52 1.25 0 .3 9 1.41 0 .5 4 1.63 1.05 1.25 1.14 1.08 1.15 1.20 1.28 1.38 0.61 2 .1 8 2 .5 9 1.24 1.21 2 .1 2 1.95 2 .1 0 1.42 2 .1 9 1.39 1.18 0 .2 6 1.84 0 .4 8 1.16 1.11 1.54 1.37 1.43 1.06 1.08 1.96 1.55 1.99 2 .1 8 2 .2 2 2 .1 5 2 .0 5 0 .9 3 1.25 0 .8 2 1.38 2 .8 8 2 .0 5 1.17 0 .2 2 2 .0 4 0 .4 0 1.06 1.63 1.72 1.25 0 .8 7 1.21 0 .9 0 1.16 1.19 1.17 2 .3 3 1.96 3 .1 8 1.66 3 .2 0 2 .9 5 1.23 1.92 2 .4 8 2 .2 6 1.22 0 .2 7 2 .3 2 0 .6 5 1.23 1.75 1.29 1.35 0 .8 5 4 .1 6 3 .8 7 3 .4 8 3 .6 5 3 .7 9 0.91 0 .9 7 1.29 1.19 1.62 4 .2 8 1.92 4 .3 3 3 .6 9 4 .9 0 1.25 0 .2 9 3.81 0 .7 8 1.10 1.25 1.17 1.06 0 .7 4 1.18 1.50 1.77 1.50 1.50 3 .7 4 3 .9 2 3.91 3 .3 4 3 .5 8 4 .0 5 4 .5 4 3 .9 2 4 .4 6 4 .8 7 1.28 0 .3 0 4 .0 3 0 .4 7 0 .8 7 0 .8 6 1.02 0 .7 7 0 .7 3 04-12-2006 Appendix to TNO-report of 3M-02 Final version Appendix D. Measurements in metabolic cages D1. Code mice and metabolic cages group# mouse# metabolic cage# 12 13 11 46 3 21 3 22 33 2247 4 31 4 32 4 37 4 38 6 51 6 53 6 54 6 55 101 105 220015 102 106 220026 103 107 203 207 104 108 204 208 04-12-2006 D2. Average bodyweight mice in metabolic cages group# mouse# metabolic cage# Bodyweight (g) Average bodyweight (g) begin metabolic cage end metabolic cage in metabolic cage 12 101 29.9 30.7 30.30 13 105 30.2 30 30.10 14 201 28 29.1 28.55 16 205 29.3 29.6 29.45 3 21 102 29.5 30.2 29.85 3 22 106 29.8 30.1 29.95 33 2247 220026 2289..85 2390..72 2299..8255 4 31 103 28.9 29.8 29.35 4 32 107 28.9 29 28.95 4 37 203 26.9 28.9 27.90 4 38 207 30.4 31.3 30.85 6 51 104 28.2 29.1 28.65 6 53 108 27.3 26.5 26.90 66 5554 220048 2297..48 2380..87 2380..3005 Page A28 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 D3. Food and drink intake measurements Food intake measurements Time (hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 Metabolic cages group 1: HF control Accumulated food intake (g) Average acc. cage 0101 cage 0105 cage 0201 cage 0205 fo o d in ta k e ( g ) 0.258 0.182 0.114 0.206 0.19 0.735 0.468 0.273 0.555 0.51 0.888 0.696 0.733 0.777 0.77 1.017 0.851 0.926 0.997 0 .9 5 1.205 0.946 1.021 1.184 1.09 1.380 1.248 1.356 1.345 1.33 1.571 1.388 1.770 1.525 1.56 1.810 1.510 2.016 1.681 1.75 2.015 1.682 2.182 1.792 1.92 2.184 1.747 2.294 1.898 2.03 2.402 1.837 2.324 1.992 2 .1 4 2.458 1.940 2.623 2.060 2.27 2.616 2.045 3.224 2.152 2.51 2.724 2.188 3.390 2.308 2 .6 5 2.824 2.437 3.480 2.473 2.80 3.064 2.599 3.486 2.689 2.96 3.300 2.792 3.510 2.748 3.09 3.564 3.013 3.525 2.995 3.27 3.879 3.109 3.676 3.304 3.49 4.146 3.214 3.802 3.448 3 .6 5 4.399 3.284 3.980 3.750 3 .8 5 4.531 3.372 4.110 3.918 3.98 4.743 3.412 4.174 3.977 4 .0 8 4.856 3.514 4.280 4.085 4 .1 8 4.935 3.602 4.321 4.343 4 .3 0 5.129 3.739 4.441 4.488 4 .4 5 5.509 4.064 4.469 4.635 4 .6 7 5.770 4.341 4.705 4.815 4.91 5.968 4.531 4.897 4.947 5.09 6.096 4.684 5.032 5.059 5.22 6.260 4.869 5.144 5.138 5 .3 5 6.378 5.016 5.351 5.318 5.52 6.529 5.181 5.535 5.470 5.68 6.741 5.397 5.692 5.729 5.89 6.916 5.608 5.944 5.965 6.11 7.046 5.794 6.060 6.139 6.26 7.233 5.993 6.328 6.449 6.50 7.443 6.101 6.615 6.749 6.73 7.561 6.231 6.776 6.879 6.86 7.629 6.317 7.002 7.007 6.99 7.763 6.406 7.175 7.153 7.12 8.003 6.555 7.392 7.280 7.31 8.140 6.690 7.504 7.345 7.42 8.297 6.796 7.656 7.432 7 .5 5 8.485 6.840 7.831 7.553 7.68 8.671 7.034 7.922 7.620 7.81 8.766 7.102 7.973 7.671 7.88 8.926 7.156 8.014 7.735 7.96 9.030 7.190 8.075 7.826 8.03 9.096 7.277 8.149 7.856 8.09 9.128 7.336 8.299 7.904 8.17 9.139 7.553 8.481 8.007 8.30 9.279 7.633 8.613 8.157 8.42 9.441 7.933 8.781 8.277 8.61 9.564 8.168 8.938 8.488 8.79 9.710 8.462 9.207 8.706 9.02 9.835 8.621 9.459 8.970 9.22 10.044 8.689 9.575 9.184 9.37 SD (g ) 0 .0 6 0 .1 9 0 .0 8 0 .0 8 0 .1 3 0 .0 6 0 .1 6 0.21 0 .2 2 0 .2 5 0 .2 7 0 .3 2 0 .5 4 0 .5 4 0 .4 8 0 .4 0 0 .3 8 0.31 0 .3 5 0.41 0 .4 6 0 .4 8 0 .5 5 0 .5 5 0 .5 5 0 .5 7 0.61 0.61 0 .6 2 0.61 0 .6 2 0 .5 9 0 .5 9 0 .5 9 0 .5 6 0 .5 4 0 .5 2 0 .5 5 0 .5 5 0 .5 4 0 .5 6 0 .5 9 0 .6 0 0 .6 2 0 .6 8 0 .6 8 0 .6 9 0 .7 4 0 .7 6 0 .7 6 0 .7 5 0 .6 8 0 .7 0 0 .6 6 0.61 0 .5 5 0 .5 3 0 .5 8 Time (hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 Metabolic cages group 3: HF + 0.03 % PFBS Accumulated food intake (g) Average acc. cage 0102 cage 0106 cage 0202 cage 0206 fo o d in ta k e ( g ) 0.215 0.190 0.188 0.203 0 .2 0 0.548 0.528 0.643 0.494 0 .5 5 0.834 0.665 0.961 0.615 0 .7 7 0.979 0.822 1.200 0.745 0 .9 4 1.156 1.081 1.312 0.890 1.11 1.416 1.340 1.505 1.058 1.33 1.624 1.437 1.738 1.282 1.52 1.828 1.652 1.911 1.374 1.69 2.005 1.696 2.105 1.503 1.83 2.164 1.772 2.282 1.601 1 .9 5 2.200 1.844 2.450 1.658 2 .0 4 2.290 1.877 2.731 1.761 2 .1 6 2.416 2.008 2.955 1.807 2 .3 0 2.506 2.171 3.097 1.885 2.41 2.638 2.304 3.284 2.120 2 .5 9 2.790 2.564 3.633 2.294 2 .8 2 3.033 2.637 3.819 2.454 2 .9 9 3.288 2.836 4.141 2.726 3 .2 5 3.478 3.028 4.557 2.931 3 .5 0 3.658 3.030 4.845 3.087 3 .6 6 3.815 3.033 4.958 3.251 3 .7 6 3.989 3.083 5.184 3.466 3 .9 3 4.160 3.140 5.331 3.592 4 .0 6 4.264 3.200 5.478 3.741 4 .1 7 4.385 3.322 5.596 3.824 4 .2 8 4.660 3.464 5.823 4.060 4 .5 0 5.208 3.675 6.138 4.316 4 .8 3 5.472 3.794 6.381 4.484 5 .0 3 5.665 4.016 6.645 4.648 5 .2 4 5.794 4.175 6.781 4.691 5 .3 6 5.890 4.375 6.887 4.736 5 .4 7 6.059 4.476 7.033 4.870 5.61 6.241 4.642 7.204 4.965 5 .7 6 6.399 4.839 7.392 5.180 5 .9 5 6.520 5.095 7.600 5.323 6 .1 3 6.764 5.403 7.862 5.512 6 .3 9 7.101 5.597 8.127 5.755 6 .6 5 7.424 5.802 8.354 6.043 6.91 7.608 5.958 8.528 6.120 7 .0 5 7.838 6.095 8.658 6.304 7 .2 2 8.024 6.240 8.807 6.420 7 .3 7 8.114 6.300 8.955 6.534 7 .4 8 8.228 6.388 9.050 6.656 7 .5 8 8.312 6.460 9.159 6.748 7 .6 7 8.479 6.546 9.299 6.817 7 .7 9 8.672 6.724 9.494 6.931 7 .9 6 8.711 6.908 9.698 6.987 8 .0 8 8.785 7.060 9.857 7.086 8 .2 0 8.830 7.178 9.942 7.105 8 .2 6 8.844 7.263 10.006 7.200 8 .3 3 8.903 7.332 10.105 7.265 8 .4 0 8.920 7.393 10.230 7.319 8 .4 7 8.996 7.574 10.390 7.448 8 .6 0 9.098 7.806 10.490 7.629 8 .7 6 9.384 7.976 10.763 7.816 8 .9 8 9.629 8.172 11.070 8.089 9 .2 4 9.819 8.314 11.308 8.285 9 .4 3 9.936 8.454 11.426 8.447 9 .5 7 SD (g ) 0.01 0 .0 6 0 .1 6 0 .2 0 0 .1 8 0 .1 9 0 .2 0 0 .2 4 0 .2 8 0 .3 2 0 .3 5 0 .4 4 0.51 0 .5 2 0.51 0 .5 8 0.61 0 .6 4 0 .7 4 0 .8 4 0 .8 6 0.91 0 .9 5 0 .9 7 0 .9 8 1.01 1.07 1.13 1.16 1.16 1 .1 4 1.16 1.18 1.17 1.16 1.16 1.20 1.20 1.23 1.23 1 .2 5 1.27 1.27 1.28 1.32 1 .3 5 1.36 1.37 1.37 1 .3 5 1.36 1.39 1.38 1.33 1.38 1.41 1 .4 4 1.42 Page A29 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Metaboliccagesgroup4: HF+0.006%PFHS Time Accumulatedfoodintake(g) Average acc. (hr) cage0103 cage0107 cage0203 cage0207 food intake (g) 6.1 0.211 0.360 0.336 0.424 0.33 7.4 0.535 0.688 0.784 0.907 0.73 8.6 0.656 0.881 1.069 1.157 0.94 9.9 0.844 1.075 1.187 1.292 1.10 11.1 0.952 1.146 1.318 1.510 1.23 12.4 1.045 1.282 1.490 1.612 1.36 13.6 1.181 1.410 1.611 1.682 1.47 14.9 1.355 1.470 1.719 1.825 1.59 16.1 1.475 1.518 1.796 1.867 1.66 17.4 1.612 1.603 1.896 2.072 1.80 18.6 1.724 1.856 2.060 2.173 1.95 19.9 1.840 2.142 2.138 2.328 2.11 21.1 2.066 2.412 2.257 2.463 2.30 22.4 2.272 2.630 2.440 2.629 2.49 23.6 2.408 2.775 2.575 2.771 2.63 24.9 2.588 2.822 2.849 2.957 2.80 26.1 2.702 2.952 3.090 3.204 2.99 27.4 2.899 3.350 3.486 3.580 3.33 28.6 3.247 3.880 3.988 4.074 3.80 29.9 3.592 4.090 4.394 4.524 4.15 31.1 3.788 4.209 4.849 4.851 4.42 32.4 3.849 4.315 5.167 5.095 4.61 33.6 3.935 4.435 5.255 5.180 4.70 34.9 4.033 4.530 5.345 5.222 4.78 36.1 4.112 4.596 5.513 5.308 4.88 37.4 4.297 4.917 5.702 5.423 5.08 38.6 4.563 5.184 5.847 5.572 5.29 39.9 4.733 5.370 5.977 5.836 5.48 41.1 4.925 5.644 6.195 5.974 5.68 42.4 5.058 5.862 6.305 6.104 5.83 43.6 5.163 6.025 6.418 6.208 5.95 44.9 5.285 6.249 6.561 6.264 6.09 46.1 5.412 6.429 6.782 6.450 6.27 47.4 5.592 6.682 7.023 6.601 6.47 48.6 5.945 6.866 7.303 6.770 6.72 49.9 6.233 7.064 7.717 6.965 6.99 51.1 6.686 7.269 8.032 7.365 7.34 52.4 7.036 7.546 8.318 7.866 7.69 53.6 7.312 7.920 8.558 8.118 7.98 54.9 7.437 8.042 8.678 8.400 8.14 56.1 7.544 8.134 8.803 8.589 8.27 57.4 7.578 8.166 8.931 8.735 8.35 58.6 7.667 8.205 9.030 8.832 8.43 59.9 7.792 8.260 9.197 8.900 8.54 61.1 7.871 8.338 9.339 9.022 8.64 62.4 7.998 8.416 9.506 9.156 8.77 63.6 8.093 8.503 9.620 9.257 8.87 64.9 8.272 8.585 9.680 9.388 8.98 66.1 8.345 8.669 9.753 9.484 9.06 67.4 8.426 8.750 9.904 9.569 9.16 68.6 8.474 8.848 10.001 9.658 9.25 69.9 8.596 8.900 10.123 9.772 9.35 71.1 8.664 9.017 10.340 9.883 9.48 72.4 8.858 9.148 10.445 10.118 9.64 73.6 9.226 9.256 10.689 10.283 9.86 74.9 9.590 9.385 10.994 10.529 10.12 76.1 9.961 9.515 11.208 10.865 10.39 77.4 10.204 9.712 11.433 11.104 10.61 SD (g) 0.09 0.16 0.22 0.19 0.24 0.25 0.23 0.22 0.20 0.23 0.20 0.20 0.18 0.17 0.18 0.16 0.22 0.30 0.38 0.41 0.52 0.64 0.63 0.62 0.65 0.62 0.56 0.56 0.55 0.55 0.55 0.56 0.59 0.62 0.57 0.61 0.55 0.54 0.52 0.54 0.56 0.61 0.62 0.63 0.66 0.69 0.70 0.66 0.66 0.69 0.71 0.72 0.77 0.76 0.74 0.76 0.78 0.79 Metaboliccagesgroup6 HF+0.003%PFOS Time Accumulatedfoodintake(g) | Average acc. (hr) cage0104cage0108 cage0204cage0208 food intake (g) 6.1 0.204 0.119 0.211 0.256 0.20 7.4 0.535 0.170 0.629 0.547 0.47 8.6 0.808 0.260 0.916 0.709 0.67 9.9 0.960 0.518 1.134 0.865 0.87 11.1 1.185 0.732 1.406 1.047 1.09 12.4 1.512 0.847 1.618 1.189 1.29 13.6 1.749 0.889 1.848 1.340 1.46 14.9 1.940 0.998 2.001 1.406 1.59 16.1 2.020 1.095 2.100 1.591 1.70 17.4 2.174 1.216 2.185 1.642 1.80 18.6 2.406 1.304 2.252 1.767 1.93 19.9 2.543 1.370 2.270 1.851 2.01 21.1 2.648 1.558 2.390 1.938 2.13 22.4 2.810 1.650 2.480 2.082 2.26 23.6 3.050 1.750 2.546 2.234 2.40 24.9 3.301 1.898 2.689 2.577 2.62 26.1 3.423 2.071 2.851 2.815 2.79 27.4 3.778 2.310 3.211 3.149 3.11 28.6 4.101 2.641 3.553 3.436 3.43 29.9 4.314 2.965 3.990 3.637 3.73 31.1 4.529 3.048 4.316 3.864 3.94 32.4 4.663 3.078 4.572 3.978 4.07 33.6 4.720 3.203 4.695 4.070 4.17 34.9 4.865 3.307 5.002 4.232 4.35 36.1 4.989 3.385 5.161 4.322 4.46 37.4 5.264 3.615 5.358 4.501 4.68 38.6 5.554 3.670 5.466 4.702 4.85 39.9 5.835 3.735 5.640 4.919 5.03 41.1 6.067 3.862 5.747 5.126 5.20 42.4 6.303 3.946 5.878 5.205 5.33 43.6 6.441 4.055 6.075 5.268 5.46 44.9 6.584 4.147 6.188 5.421 5.59 46.1 6.733 4.293 6.320 5.543 5.72 47.4 7.107 4.400 6.508 5.644 5.91 48.6 7.672 4.522 6.617 5.846 6.16 49.9 7.929 4.758 6.854 6.035 6.39 51.1 8.198 5.100 7.194 6.268 6.69 52.4 8.427 5.352 7.512 6.465 6.94 53.6 8.566 5.511 7.721 6.688 7.12 54.9 8.762 5.603 7.901 6.921 7.30 56.1 8.892 5.689 8.062 7.030 7.42 57.4 9.088 5.749 8.139 7.093 7.52 58.6 9.207 5.852 8.244 7.166 7.62 59.9 9.378 6.024 8.302 7.200 7.73 61.1 9.554 6.105 8.386 7.307 7.84 62.4 9.689 6.228 8.526 7.433 7.97 63.6 9.839 6.294 8.674 7.524 8.08 64.9 10.003 6.361 8.830 7.611 8.20 66.1 10.139 6.478 8.880 7.664 8.29 67.4 10.256 6.542 8.933 7.717 8.36 68.6 10.347 6.591 9.006 7.720 8.42 69.9 10.464 6.718 9.083 7.740 8.50 71.1 10.593 6.810 9.309 7.807 8.63 72.4 10.793 6.915 9.451 7.914 8.77 73.6 11.011 7.103 9.579 8.188 8.97 74.9 11.264 7.345 9.788 8.977 9.34 76.1 11.518 7.679 10.107 9.184 9.62 77.4 11.641 7.878 10.312 9.426 9.81 SD (g) 0.06 0.20 0.29 0.26 0.28 0.35 0.44 0.47 0.46 0.47 0.50 0.51 0.48 0.50 0.55 0.57 0.55 0.60 0.60 0.58 0.66 0.73 0.71 0.77 0.81 0.81 0.87 0.95 0.97 1.03 1.06 1.07 1.07 1.17 1.33 1.34 1.32 1.33 1.32 1.36 1.38 1.43 1.44 1.44 1.48 1.48 1.52 1.57 1.58 1.60 1.62 1.63 1.66 1.71 1.70 1.63 1.61 1.58 Page A30 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Time ( hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 2 2 .4 2 3 .6 2 4 .9 26.1 2 7 .4 2 8 .6 2 9 .9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 4 2 .4 4 3 .6 4 4 .9 46.1 4 7 .4 4 8 .6 4 9 .9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 6 2 .4 6 3 .6 6 4 .9 66.1 6 7 .4 6 8 .6 6 9 .9 71.1 72.4 73.6 74.9 76.1 77.4 group 1 vs 3 nn p 4 4 0.886 4 4 0.886 4 4 0.886 4 4 0.686 4 4 1.000 4 4 0.886 4 4 0.886 4 4 0.886 4 4 0.686 4 4 0.686 4 4 0.686 4 4 0.686 4 4 0.486 4 4 0.486 4 4 0.486 4 4 0.686 4 4 0.686 4 4 0.686 4 4 0.686 4 4 0.686 4 4 0.686 4 4 0.886 4 4 0.886 4 4 0.886 4 4 1.000 4 4 1.000 4 4 1.000 4 4 1.000 4 4 1.000 4 4 1.000 4 4 0.860 4 4 0.886 4 4 0.886 4 4 0.886 4 4 0.886 4 4 0.886 4 4 0.886 4 4 0.886 4 4 1.000 4 4 1.000 4 4 0.886 4 4 1.000 4 4 1.000 4 4 1.000 4 4 0.886 4 4 0.886 4 4 0.886 4 4 0.886 4 4 0.886 4 4 0.886 4 4 0.886 4 4 0.886 4 4 0.886 4 4 0.886 4 4 0.886 4 4 0.886 4 4 0.886 4 4 0.886 Accumulated Food intake; p-values Mann Whitney U-test group 1 vs 4 group 1 vs 6 group 3 vs 4 group 3 vs 6 group 4 vs 6 n n p nn n nn 4 0.057 4 0.860 0.057 4 0 .6 8 6 0 .0 5 7 4 0.200 4 0.886 0.114 4 0 .8 8 6 0 .1 1 4 4 0.486 4 1.000 0.343 4 0 .8 8 6 0 .3 4 3 4 0.343 4 0.886 0.343 4 0 .8 8 6 0 .3 4 3 4 0.486 4 0.886 0.486 4 1.000 0 .6 8 6 4 0.886 4 1.000 1.000 4 0 .8 8 6 1.000 4 0.886 4 0.886 0.686 4 0 .8 8 6 0 .8 8 6 4 0.486 4 0.686 0.486 4 0 .8 8 6 0 .8 8 6 4 0.343 4 0.486 0.486 4 0 .8 8 6 0 .6 8 6 4 0.200 4 0.486 0.486 4 0 .8 8 6 0 .6 8 6 4 0.486 4 0.686 0.886 4 0 .8 8 6 0 .8 8 6 4 0.686 4 0.486 1.000 4 0 .6 8 6 1.000 4 0.886 4 0.486 0.886 4 0 .6 8 6 0 .6 8 6 4 0.886 4 0.486 0.686 4 0 .6 8 6 0 .6 8 6 4 0.686 4 0.486 0.686 4 0 .6 8 6 0 .4 8 6 4 0.686 4 0.343 0.486 4 0 .8 8 6 0 .4 8 6 4 0.686 4 0.886 0.686 4 0 .8 8 6 0 .6 8 6 4 1.000 4 1.000 0.486 4 0 .8 8 6 0 .6 8 6 4 0.200 4 1.000 0.486 4 1.000 0 .6 8 6 4 0.200 4 0.886 0.486 4 1.000 0 .3 4 3 4 0.200 4 0.886 0.486 4 0 .6 8 6 0 .4 8 6 4 0.343 4 0.686 0.486 4 0 .8 8 6 0 .4 8 6 4 0.343 4 1.000 0.486 4 0 .8 8 6 0 .4 8 6 4 0.343 4 0.686 0.486 4 0 .8 8 6 0 .4 8 6 4 0.343 4 0.686 0.486 4 0 .8 8 6 0 .4 8 6 4 0.343 4 0.486 0.486 4 0 .8 8 6 0 .4 8 6 4 0.200 4 0.686 0.686 4 1.000 0 .4 8 6 4 0.200 4 0.686 0.686 4 1.000 0 .4 8 6 4 0.200 4 0.686 0.686 4 1.000 0 .6 8 6 4 0.200 4 0.686 0.486 4 1.000 0 .6 8 6 4 0.200 4 0.686 0.486 4 1.000 0 .8 8 6 4 0.486 4 0.686 0.486 4 1.000 0 .6 8 6 4 0.486 4 0.686 0.486 4 1.000 0 .4 8 6 4 0.486 4 1.000 0.486 4 1.000 0 .6 8 6 4 0.343 4 1.000 0.486 4 0 .8 8 6 0 .4 8 6 4 0.114 4 1.000 0.486 4 0 .8 8 6 0 .4 8 6 4 0.057 4 1.000 0.486 4 0 .8 8 6 0 .4 8 6 4 0.057 4 0.886 0.486 4 0 .8 8 6 0 .4 8 6 4 0.057 4 0.886 0.343 4 0 .8 8 6 0 .4 8 6 4 0.057 4 0.886 0.343 4 0 .8 8 6 0 .4 8 6 4 0.057 4 0.886 0.486 4 0 .8 8 6 0 .4 8 6 4 0.057 4 0.886 0.486 4 0 .8 8 6 0 .4 8 6 4 0.057 4 0.886 0.686 4 0 .8 8 6 0 .6 8 6 4 0.114 4 0.886 0.486 4 1.000 0 .6 8 6 4 0.114 4 1.000 0.486 4 1.000 0 .6 8 6 4 0.114 4 1.000 0.486 4 1.000 0 .6 8 6 4 0.114 4 1.000 0.686 4 1.000 0 .6 8 6 4 0.114 4 1.000 0.686 4 0 .8 8 6 0 .6 8 6 4 0.114 4 1.000 0.686 4 0 .8 8 6 0 .6 8 6 4 0.114 4 1.000 0.686 4 0 .8 8 6 0 .6 8 6 4 0.114 4 1.000 0.686 4 0 .8 8 6 0 .6 8 6 4 0.114 4 1.000 0.686 4 0 .8 8 6 0 .6 8 6 4 0.114 4 0.886 0.486 4 0 .8 8 6 0 .6 8 6 4 0.114 4 1.000 0.486 4 0 .8 8 6 0 .6 8 6 4 0.114 4 0.886 0.686 4 0 .8 8 6 0 .6 8 6 4 0.114 4 0.686 0.686 4 0 .8 8 6 0 .6 8 6 4 0.057 4 0.686 0.486 4 0 .8 8 6 0 .6 8 6 4 0.057 4 0.686 0.343 4 0 .8 8 6 0 .6 8 6 p< 0 .0 5 Page A31 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Feeding bout size measurements Metaboliccagesgroup1: HFcontrol Time Feedingboutsize(g) Average feeding SD J6M.1 cage0101 cage0105 cage0201 cage0205 bout size (g) 0.045 0.036 0.018 0.044 0.036 (g) 0.013 7.4 0.043 0.019 0.032 0.025 0.030 0.010 8.6 0.002 0.029 0.034 0.018 0.021 0.014 9.9 0.018 0.002 0.012 0.025 0.014 0.010 11.1 0.017 0.014 0.010 0.008 0.012 0.004 12.4 0.022 0.032 0.053 0.022 0.032 0.015 13.6 0.024 0.013 0.038 0.017 0.023 0.011 14.9 0.023 0.017 0.018 0.013 0.018 0.004 16.1 0.013 0.010 0.005 0.013 0.010 0.004 17.4 0.014 0.005 0.012 0.012 0.011 0.004 18.6 0.023 0.013 0.002 0.003 0.010 0.010 19.9 0.006 0.005 0.078 0.012 0.025 0.035 21.1 0.019 0.014 0.015 0.008 0.014 0.005 22.4 0.008 0.028 0.021 0.014 0.018 0.009 23.6 0.017 0.020 0.000 0.025 0.016 0.011 24.9 0.016 0.005 0.003 0.011 0.009 0.006 26.1 0.038 0.030 0.000 0.016 0.021 0.017 27.4 0.012 0.012 0.005 0.026 0.014 0.009 28.6 0.040 0.011 0.021 0.028 0.025 0.012 29.9 0.029 0.011 0.021 0.009 0.018 0.009 31.1 0.015 0.010 0.000 0.042 0.017 0.018 32.4 0.025 0.002 0.016 0.004 0.012 0.011 33.6 0.011 0.008 0.006 0.003 0.007 0.003 34.9 0.007 0.009 0.008 0.015 0.010 0.004 36.1 0.016 0.016 0.008 0.033 0.018 0.011 37.4 0.031 0.004 0.009 0.010 0.014 0.012 38.6 0.026 0.046 0.011 0.015 0.025 0.016 39.9 0.026 0.025 0.025 0.015 0.023 0.005 41.1 0.018 0.012 0.013 0.010 0.013 0.003 42.4 0.012 0.017 0.010 0.011 0.013 0.003 43.6 0.021 0.014 0.013 0.017 0.016 0.004 44.9 0.008 0.018 0.024 0.017 0.017 0.007 46.1 0.018 0.023 0.021 0.021 0.021 0.002 47.4 0.023 0.020 0.018 0.020 0.020 0.002 48.6 0.009 0.023 0.021 0.017 0.018 0.006 49.9 0.021 0.017 0.012 0.028 0.020 0.007 51.1 0.025 0.014 0.038 0.030 0.027 0.010 52.4 0.010 0.014 0.025 0.029 0.020 0.009 53.6 0.008 0.009 0.008 0.011 0.009 0.001 54.9 0.011 0.009 0.023 0.015 0.015 0.006 56.1 0.013 0.013 0.021 0.016 0.016 0.004 57.4 0.027 0.012 0.015 0.000 0.014 0.011 58.6 0.019 0.012 0.016 0.007 0.014 0.005 59.9 0.007 0.009 0.015 0.018 0.012 0.005 61.1 0.029 0.004 0.013 0.009 0.014 0.011 62.4 0.011 0.020 0.008 0.000 0.010 0.008 63.6 0.002 0.005 0.004 0.008 0.005 0.003 64.9 0.024 0.007 0.008 0.012 0.013 0.008 66.1 0.002 0.002 0.001 0.001 0.002 0.001 67.4 0.008 0.010 0.018 0.003 0.010 0.006 68.6 0.001 0.015 0.009 0.014 0.010 0.006 69.9 0.002 0.017 0.017 0.001 0.009 0.009 71.1 0.017 0.002 0.014 0.021 0.014 0.008 72.4 0.018 0.047 0.019 0.015 0.025 0.015 73.6 0.009 0.012 0.017 0.027 0.016 0.008 74.9 0.019 0.038 0.035 0.020 0.028 0.010 76.1 0.021 0.002 0.013 0.027 0.016 0.011 77.4 0.010 0.010 0.015 0.014 0.012 0.003 Metaboliccagesgroup3: HF+0.03% PFBS Time Feedingboutsize(g) Average feeding SD (hr) cage0102 cage0106 cage0202 cage0206 bout size (g) (g) 6.1 0.045 0.043 0.032 0.041 0.040 0.006 7.4 0.018 0.018 0.038 0.010 0.021 0.012 8.6 0.024 0.011 0.033 0.014 0.021 0.010 9.9 0.017 0.026 0.025 0.015 0.021 0.006 11.1 0.036 0.024 0.008 0.015 0.021 0.012 12.4 0.002 0.019 0.026 0.020 0.017 0.010 13.6 0.036 0.017 0.018 0.020 0.023 0.009 14.9 0.012 0.008 0.024 0.008 0.013 0.008 16.1 0.015 0.011 0.019 0.011 0.014 0.004 17.4 0.013 0.001 0.013 0.007 0.009 0.006 18.6 0.010 0.008 0.015 0.012 0.011 0.003 19.9 0.001 0.004 0.028 0.005 0.010 0.012 21.1 0.018 0.018 0.024 0.003 0.016 0.009 22.4 0.012 0.019 0.009 0.015 0.014 0.004 23.6 0.009 0.007 0.025 0.020 0.015 0.009 24.9 0.015 0.028 0.036 0.027 0.027 0.009 26.1 0.028 0.009 0.021 0.012 0.018 0.009 27.4 0.028 0.031 0.046 0.029 0.034 0.008 28.6 0.020 0.001 0.027 0.021 0.017 0.011 29.9 0.011 0.000 0.024 0.009 0.011 0.010 31.1 0.024 0.003 0.016 0.029 0.018 0.011 32.4 0.022 0.008 0.012 0.009 0.013 0.006 33.6 0.000 0.000 0.023 0.008 0.008 0.011 34.9 0.014 0.011 0.010 0.018 0.013 0.004 36.1 0.013 0.012 0.015 0.012 0.013 0.001 37.4 0.055 0.010 0.031 0.032 0.032 0.018 38.6 0.044 0.025 0.028 0.016 0.028 0.012 39.9 0.009 0.012 0.032 0.020 0.018 0.010 41.1 0.027 0.031 0.012 0.009 0.020 0.011 42.4 0.006 0.015 0.011 0.003 0.009 0.005 43.6 0.014 0.011 0.020 0.012 0.014 0.004 44.9 0.010 0.009 0.010 0.010 0.010 0.001 46.1 0.023 0.017 0.018 0.016 0.019 0.003 47.4 0.017 0.032 0.017 0.022 0.022 0.007 48.6 0.005 0.033 0.024 0.011 0.018 0.013 49.9 0.038 0.022 0.025 0.024 0.027 0.007 51.1 0.032 0.019 0.032 0.024 0.027 0.006 52.4 0.030 0.018 0.020 0.023 0.023 0.005 53.6 0.013 0.008 0.014 0.000 0.009 0.006 54.9 0.025 0.015 0.011 0.026 0.019 0.007 56.1 0.015 0.010 0.023 0.008 0.014 0.007 57.4 0.014 0.006 0.004 0.017 0.010 0.006 58.6 0.007 0.013 0.015 0.010 0.011 0.004 59.9 0.013 0.011 0.007 0.002 0.008 0.005 61.1 0.020 0.001 0.022 0.012 0.014 0.010 62.4 0.008 0.030 0.022 0.011 0.018 0.010 63.6 0.004 0.009 0.007 0.002 0.006 0.003 64.9 0.011 0.019 0.020 0.010 0.015 0.005 66.1 0.000 0.011 0.005 0.001 0.004 0.005 67.4 0.007 0.007 0.006 0.014 0.009 0.004 68.6 0.002 0.005 0.013 0.006 0.007 0.005 69.9 0.000 0.011 0.009 0.002 0.006 0.005 71.1 0.013 0.023 0.018 0.022 0.019 0.005 72.4 0.014 0.023 0.010 0.014 0.015 0.006 73.6 0.033 0.008 0.041 0.019 0.025 0.015 74.9 0.019 0.023 0.022 0.032 0.024 0.006 76.1 0.017 0.008 0.021 0.017 0.016 0.006 77.4 0.006 0.015 0.010 0.013 0.011 0.004 Page A32 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Metaboliccagesgroup4: HF+0.006%PFHS Time Feedingboutsize(g) Average feeding (hr) cage0103 cage0107 cage0203cage0207 bout size (g) 6.1 0.043 0.050 0.060 0.066 0.055 7.4 0.019 0.023 0.037 0.037 0.029 8.6 0.009 0.023 0.014 0.025 0.018 9.9 0.022 0.014 0.011 0.009 0.014 11.1 0.007 0.007 0.025 0.021 0.015 12.4 0.010 0.024 0.006 0.004 0.011 13.6 0.020 0.000 0.015 0.020 0.014 14.9 0.010 0.006 0.011 0.001 0.007 16.1 0.013 0.005 0.006 0.019 0.011 17.4 0.013 0.012 0.007 0.012 0.011 18.6 0.011 0.027 0.021 0.005 0.016 19.9 0.021 0.040 0.008 0.023 0.023 21.1 0.018 0.013 0.014 0.008 0.013 22.4 0.016 0.029 0.010 0.021 0.019 23.6 0.015 0.009 0.025 0.013 0.016 24.9 0.019 0.001 0.024 0.024 0.017 26.1 0.009 0.019 0.024 0.030 0.021 27.4 0.036 0.063 0.056 0.041 0.049 28.6 0.033 0.030 0.044 0.048 0.039 29.9 0.024 0.020 0.049 0.049 0.036 31.1 0.014 0.012 0.036 0.017 0.020 32.4 0.005 0.009 0.019 0.025 0.015 33.6 0.010 0.017 0.005 0.000 0.008 34.9 0.012 0.000 0.018 0.010 0.010 36.1 0.009 0.012 0.013 0.008 0.011 37.4 0.028 0.032 0.015 0.007 0.021 38.6 0.019 0.040 0.020 0.030 0.027 39.9 0.017 0.000 0.012 0.019 0.012 41.1 0.022 0.044 0.021 0.011 0.025 42.4 0.009 0.015 0.007 0.011 0.011 43.6 0.007 0.016 0.010 0.008 0.010 44.9 0.012 0.017 0.030 0.019 0.020 46.1 0.013 0.035 0.011 0.010 0.017 47.4 0.028 0.007 0.029 0.017 0.020 48.6 0.037 0.026 0.037 0.017 0.029 49.9 0.033 0.015 0.035 0.022 0.026 51.1 0.040 0.027 0.027 0.060 0.039 52.4 0.030 0.039 0.032 0.026 0.032 53.6 0.022 0.025 0.023 0.036 0.027 54.9 0.013 0.004 0.001 0.020 0.010 56.1 0.008 0.008 0.021 0.016 0.013 57.4 0.006 0.002 0.006 0.014 0.007 58.6 0.014 0.007 0.018 0.006 0.011 59.9 0.004 0.005 0.017 0.007 0.008 61.1 0.011 0.008 0.015 0.018 0.013 62.4 0.014 0.012 0.014 0.011 0.013 63.6 0.017 0.002 0.009 0.009 0.009 64.9 0.008 0.015 0.000 0.014 0.009 66.1 0.011 0.009 0.022 0.009 0.013 67.4 0.006 0.000 0.001 0.008 0.004 68.6 0.001 0.010 0.017 0.008 0.009 69.9 0.014 0.010 0.013 0.013 0.013 71.1 0.006 0.014 0.015 0.013 0.012 72.4 0.034 0.013 0.011 0.024 0.021 73.6 0.041 0.008 0.035 0.023 0.027 74.9 0.034 0.015 0.030 0.025 0.026 76.1 0.037 0.016 0.019 0.036 0.027 77.4 0.017 0.014 0.025 0.013 0.017 SD (g) 0.010 0.009 0.008 0.006 0.009 0.009 0.009 0.005 0.007 0.003 0.010 0.013 0.004 0.008 0.007 0.011 0.009 0.013 0.009 0.016 0.011 0.009 0.007 0.007 0.002 0.012 0.010 0.009 0.014 0.003 0.004 0.008 0.012 0.010 0.010 0.009 0.016 0.005 0.006 0.009 0.006 0.005 0.006 0.006 0.004 0.002 0.006 0.007 0.006 0.004 0.007 0.002 0.004 0.011 0.015 0.008 0.011 0.005 Metaboliccagesgroup6 HF+0.003%PFOS Time Feedingboutsize(g) | Average feeding (hr) cage0104cage0108cage0204cage0208 bout size (g) 6.1 0.040 0.017 0.037 0.035 0.032 7.4 0.026 0.000 0.043 0.025 0.024 8.6 0.020 0.010 0.018 0.018 0.017 9.9 0.024 0.036 0.025 0.018 0.026 11.1 0.022 0.015 0.027 0.013 0.019 12.4 0.030 0.009 0.027 0.014 0.020 13.6 0.027 0.003 0.014 0.014 0.015 14.9 0.008 0.019 0.019 0.008 0.014 16.1 0.010 0.001 0.000 0.018 0.007 17.4 0.026 0.013 0.009 0.002 0.013 18.6 0.014 0.013 0.007 0.012 0.012 19.9 0.011 0.008 0.010 0.013 0.011 21.1 0.015 0.017 0.011 0.013 0.014 22.4 0.019 0.010 0.004 0.014 0.012 23.6 0.024 0.013 0.006 0.015 0.015 24.9 0.018 0.010 0.023 0.033 0.021 26.1 0.013 0.031 0.015 0.033 0.023 27.4 0.050 0.013 0.049 0.024 0.034 28.6 0.020 0.046 0.029 0.033 0.032 29.9 0.027 0.016 0.031 0.011 0.021 31.1 0.013 0.006 0.035 0.024 0.020 32.4 0.014 0.003 0.023 0.011 0.013 33.6 0.010 0.016 0.017 0.012 0.014 34.9 0.011 0.012 0.036 0.019 0.020 36.1 0.011 0.004 0.004 0.002 0.005 37.4 0.039 0.023 0.022 0.023 0.027 38.6 0.029 0.007 0.014 0.022 0.018 39.9 0.024 0.013 0.012 0.026 0.019 41.1 0.023 0.004 0.013 0.014 0.014 42.4 0.018 0.016 0.017 0.002 0.013 43.6 0.013 0.003 0.011 0.012 0.010 44.9 0.020 0.020 0.012 0.013 0.016 46.1 0.013 0.010 0.015 0.015 0.013 47.4 0.066 0.010 0.020 0.018 0.029 48.6 0.026 0.016 0.019 0.012 0.018 49.9 0.031 0.029 0.032 0.019 0.028 51.1 0.027 0.029 0.031 0.027 0.029 52.4 0.021 0.019 0.029 0.023 0.023 53.6 0.012 0.014 0.017 0.014 0.014 54.9 0.014 0.012 0.016 0.026 0.017 56.1 0.019 0.005 0.012 0.005 0.010 57.4 0.015 0.006 0.005 0.011 0.009 58.6 0.015 0.014 0.014 0.001 0.011 59.9 0.014 0.015 0.001 0.006 0.009 61.1 0.023 0.010 0.014 0.013 0.015 62.4 0.012 0.013 0.014 0.010 0.012 63.6 0.016 0.001 0.021 0.008 0.012 64.9 0.015 0.017 0.005 0.009 0.012 66.1 0.010 0.002 0.005 0.008 0.006 67.4 0.012 0.008 0.007 0.001 0.007 68.6 0.011 0.003 0.009 0.000 0.006 69.9 0.012 0.014 0.006 0.007 0.010 71.1 0.009 0.014 0.027 0.003 0.013 72.4 0.022 0.008 0.011 0.020 0.015 73.6 0.028 0.028 0.021 0.087 0.041 74.9 0.027 0.021 0.019 0.015 0.021 76.1 0.020 0.031 0.036 0.030 0.029 77.4 0.007 0.016 0.013 0.016 0.013 SD (g) 0.010 0.018 0.004 0.008 0.006 0.010 0.010 0.006 0.008 0.010 0.003 0.002 0.003 0.006 0.007 0.010 0.010 0.018 0.011 0.009 0.013 0.008 0.003 0.012 0.004 0.008 0.010 0.007 0.008 0.008 0.005 0.004 0.002 0.025 0.006 0.006 0.002 0.004 0.002 0.006 0.007 0.005 0.007 0.007 0.006 0.002 0.009 0.006 0.004 0.005 0.005 0.004 0.010 0.007 0.031 0.005 0.007 0.004 Page A33 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Time ( hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 2 2 .4 2 3 .6 2 4 .9 26.1 2 7 .4 2 8 .6 2 9 .9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 4 2 .4 4 3 .6 4 4 .9 46.1 4 7 .4 4 8 .6 4 9 .9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 6 2 .4 6 3 .6 6 4 .9 66.1 6 7 .4 6 8 .6 6 9 .9 71.1 7 2 .4 7 3 .6 7 4 .9 76.1 7 7 .4 group 1 vs 3 nn p 4 4 0.886 4 4 0.200 4 4 0.886 4 4 0.343 4 4 0.343 4 4 0.114 4 4 0.886 4 4 0.343 4 4 0.343 4 4 0.886 4 4 0.886 4 4 0.200 4 4 0.686 4 4 0.686 4 4 1.000 4 4 0.057 4 4 0.686 4 4 0.029 4 4 0.343 4 4 0.486 4 4 0.686 4 4 0.886 4 4 0.686 4 4 0.200 4 4 0.343 4 4 0.114 4 4 0.686 4 4 0.486 4 4 0.686 4 4 0.343 4 4 0.343 4 4 0.343 4 4 0.343 4 4 0.886 4 4 0.886 4 4 0.200 4 4 1.000 4 4 0.686 4 4 0.886 4 4 0.343 4 4 0.686 4 4 0.886 4 4 0.486 4 4 0.343 4 4 1.000 4 4 0.343 4 4 0.886 4 4 0.686 4 4 0.886 4 4 0.686 4 4 0.486 4 4 0.460 4 4 0.343 4 4 0.200 4 4 0.486 4 4 0.686 4 4 0.686 4 4 0.686 gr n 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 Feeding bout size; p-values Mann Whitney U-test 1 vs 4 p 0 .1 1 4 group 1 vs 6 np 0 .4 8 6 group 3 vs 4 4 n r 0 .0-5 7 group 3 vs 6 np 4 0.200 group 4 vs 6 nn p 0 .0 2 9 0 .8 8 6 0.886 4 0.343 4 0 .6 8 6 1.000 0 .6 8 6 0.686 4 0.686 4 0 .6 8 6 0 .8 8 6 0 .8 8 6 0.200 4 0.114 4 0 .4 8 6 0 .0 5 7 1.000 0.200 4 0.486 4 0 .8 8 6 0 .4 8 6 0 .1 1 4 0.343 4 0.686 4 0 .6 8 6 0 .2 0 0 0 .4 8 6 0.486 4 0.486 4 0.200 0 .8 8 6 0 .0 2 9 0.686 4 0.343 4 1.000 0 .3 4 3 0 .8 8 6 0.486 4 0.486 4 0.200 0 .4 8 6 1.000 1.000 4 0.886 4 0 .6 8 6 0 .8 8 6 0 .4 8 6 0.686 4 0.686 4 0 .8 8 6 0 .8 8 6 0 .4 8 6 0.886 4 0.200 4 0 .3 4 3 0 .2 0 0 0 .6 8 6 0.886 4 0.486 4 0 .3 4 3 0 .8 8 6 0 .6 8 6 0.343 4 0.343 4 0 .6 8 6 0 .2 0 0 0 .6 8 6 0.686 4 0.886 4 0 .8 8 6 0 .8 8 6 0 .3 4 3 0.114 4 0.200 4 0 .4 8 6 1.000 0 .8 8 6 1.000 4 0.686 4 0 .3 4 3 0 .6 8 6 0 .0 2 9 0.114 4 0.114 4 1.000 0 .3 4 3 0 .1 1 4 0.486 4 0.029 4 0 .1 1 4 0 .3 4 3 0.200 0.486 4 0.057 4 0 .1 1 4 0 .3 4 3 0 .6 8 6 0.886 4 1.000 4 0 .8 8 6 0 .8 8 6 0 .4 8 6 1.000 4 0.886 4 0 .8 8 6 0 .8 8 6 1.000 0.057 4 0.886 4 0 .3 4 3 0 .3 4 3 0 .6 8 6 0.114 4 0.686 4 0 .3 4 3 0 .2 0 0 0.200 0.057 4 0.200 4 0 .0 2 9 0 .1 1 4 0 .4 8 6 0.200 4 0.343 4 0 .6 8 6 0 .6 8 6 0 .6 8 6 0.686 4 1.000 4 0 .3 4 3 0 .3 4 3 0 .1 1 4 0.343 4 0.486 4 0 .6 8 6 0 .3 4 3 0.200 0.686 4 0.860 4 0 .6 8 6 0 .4 8 6 0 .3 4 3 0.486 4 0.686 4 0 .3 4 3 0 .3 4 3 0 .1 1 4 0.029 4 0.200 4 0 .3 4 3 0 .8 8 6 0 .6 8 6 1.000 4 0.029 4 0 .0 2 9 0 .8 8 6 0 .3 4 3 0.029 4 0.343 4 0 .0 2 9 0 .8 8 6 1.000 0.686 4 0.886 4 1.000 0 .8 8 6 0 .1 1 4 1.000 4 0.200 4 0 .8 8 6 0 .1 1 4 0 .3 4 3 0.140 4 0.686 4 0 .8 8 6 0 .8 8 6 0 .3 4 3 0.886 4 0.343 4 1.000 0 .6 8 6 0 .0 5 7 0.686 4 0.057 4 0 .8 8 6 0 .0 5 7 0 .0 2 9 0.029 4 0.029 4 0.200 0 .0 2 9 0 .4 8 6 0.486 4 0.200 4 0 .8 8 6 0 .3 4 3 0 .6 8 6 0.200 4 0.886 4 0 .4 8 6 0 .4 8 6 0 .4 8 6 0.486 4 0.486 4 0 .8 8 6 0 .6 8 6 0 .4 8 6 0.686 4 0.886 4 0 .6 8 6 1.000 0.200 0.343 4 0.886 4 0 .8 8 6 1.000 0 .8 8 6 0.486 4 0.686 4 0 .8 8 6 0 .8 8 6 0 .3 4 3 0.486 4 0.886 4 0 .8 8 6 0 .6 8 6 0.200 0.343 4 0.343 4 0 .4 8 6 1.000 0 .8 8 6 1.000 4 0.343 4 0 .3 4 3 0 .4 8 6 0 .0 2 9 0.057 4 0.114 4 0 .4 8 6 0 .1 1 4 0 .1 1 4 0.486 4 0.200 4 1.000 0 .3 4 3 0 .8 8 6 0.343 4 0.686 4 0 .8 8 6 0 .6 8 6 1.000 1.000 4 0.057 4 0 .3 4 3 0 .3 4 3 0 .4 8 6 0.886 4 0.114 4 0 .4 8 6 0 .8 8 6 0 .6 8 6 0.686 4 0.686 4 0 .8 8 6 0 .3 4 3 0 .4 8 6 0.057 4 0.886 4 0 .6 8 6 0 .8 8 6 0 .6 8 6 0.343 4 0.686 4 0 .3 4 3 0 .3 4 3 0 .3 4 3 0.114 4 0.343 4 0 .0 5 7 0 .8 8 6 0.200 0.686 4 0.114 4 0 .3 4 3 0 .3 4 3 p< 0 .0 5 Page A34 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Drink intake measurements Time (hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 Metabolic cages group 1: HF control Accumulated drink intake (ml) Average acc. cage 0101 cage 0105 cage 0201 cage 0205 d rin k intake (ml) 0.205 0.065 0.129 0.230 0.16 0.720 0.337 0.591 0.580 0.56 0.946 0.658 0.782 0.846 0.81 1.053 0.791 0.784 1.083 0.93 1.209 0.845 0.805 1.297 1.04 1.284 1.166 0.936 1.334 1.18 1.375 1.292 1.208 1.481 1.34 1.602 1.326 1.325 1.610 1.47 1.716 1.448 1.348 1.624 1.53 1.799 1.479 1.373 1.702 1.59 1.836 1.499 1.382 1.806 1.63 1.898 1.530 1.463 1.826 1.68 1.981 1.530 1.564 1.863 1.73 2.002 1.530 1.576 1.891 1.75 2.049 1.778 1.610 1.976 1.85 2.213 1.870 1.610 2.024 1.93 2.280 2.047 1.796 2.024 2.04 2.465 2.264 1.927 2.098 2.19 2.714 2.349 2.268 2.291 2.41 3.045 2.480 2.638 2.436 2.65 3.250 2.581 2.921 2.691 2.86 3.375 2.669 3.022 2.949 3.00 3.523 2.720 3.227 2.967 3.11 3.640 2.863 3.434 3.036 3.24 3.734 3.104 3.738 3.252 3.46 3.796 3.281 3.818 3.353 3.56 4.053 3.602 4.089 3.434 3.79 4.358 3.893 4.292 3.680 4.06 4.508 4.029 4.460 3.765 4.19 4.524 4.072 4.508 3.832 4.23 4.654 4.114 4.517 3.885 4.29 4.716 4.201 4.683 4.004 4.40 4.784 4.325 4.812 4.170 4.52 4.966 4.510 4.908 4.342 4.68 5.096 4.661 5.072 4.499 4.83 5.140 4.925 5.175 4.538 4.94 5.200 5.018 5.251 4.664 5.03 5.343 5.110 5.469 4.848 5.19 5.465 5.280 5.699 4.922 5.34 5.530 5.423 5.895 5.037 5.47 5.694 5.540 6.008 5.175 5.60 5.892 5.799 6.279 5.348 5.83 6.146 5.984 6.385 5.428 5.99 6.297 6.086 6.578 5.481 6.11 6.399 6.137 6.760 5.557 6.21 6.604 6.372 6.937 5.612 6.38 6.604 6.499 7.038 5.653 6.45 6.695 6.511 7.075 5.773 6.51 6.796 6.511 7.222 5.865 6.60 6.812 6.547 7.270 5.865 6.62 6.812 6.562 7.447 5.900 6.68 6.812 6.800 7.544 6.056 6.80 6.942 6.848 7.694 6.148 6.91 7.192 7.031 7.822 6.297 7.09 7.311 7.293 7.852 6.387 7.21 7.535 7.560 8.022 6.608 7.43 7.639 7.701 8.317 6.845 7.63 7.875 7.752 8.349 7.043 7.75 SD (m l) 0.08 0.16 0.12 0.16 0.25 0.18 0.12 0.16 0.17 0.20 0.22 0.21 0.22 0.23 0.20 0.25 0.20 0.23 0.21 0.28 0.30 0.29 0.34 0.36 0.33 0.28 0.33 0.32 0.36 0.34 0.36 0.35 0.32 0.30 0.30 0.29 0.27 0.27 0.33 0.35 0.35 0.38 0.41 0.47 0.51 0.56 0.58 0.55 0.57 0.59 0.64 0.61 0.63 0.63 0.61 0.59 0.60 0.54 Time (hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 Metabolic cages group 3: HF + 0.03 % PFBS Accumulated drink intake (ml) Average acc. cage 0102 cage 0106 cage 0202 cage 0206 d rin k intake (ml) 0.125 0.077 0.074 0.092 0.09 0.387 0.392 0.569 0.388 0.43 0.699 0.496 0.967 0.560 0.68 0.883 0.510 1.102 0.676 0.79 0.912 0.691 1.253 0.864 0.93 0.994 0.800 1.449 1.024 1.07 1.176 0.824 1.634 1.276 1.23 1.318 0.834 1.800 1.400 1.34 1.462 0.848 1.850 1.400 1.39 1.565 0.861 2.153 1.450 1.51 1.592 0.872 2.254 1.500 1.55 1.600 0.880 2.311 1.500 1.57 1.659 0.880 2.578 1.548 1.67 1.730 0.923 2.743 1.616 1.75 1.768 1.003 2.804 1.780 1.84 1.837 1.013 3.065 1.842 1.94 1.898 1.024 3.283 1.988 2.05 2.045 1.078 3.512 2.146 2.20 2.210 1.179 3.904 2.280 2.39 2.357 1.194 4.171 2.418 2.53 2.539 1.205 4.361 2.606 2.68 2.710 1.216 4.558 2.764 2.81 2.912 1.232 4.669 2.906 2.93 2.968 1.245 4.869 2.988 3.02 3.101 1.302 4.941 3.026 3.09 3.251 1.360 5.004 3.248 3.22 3.547 1.386 5.263 3.424 3.41 3.787 1.453 5.465 3.520 3.56 3.955 1.557 5.645 3.520 3.67 4.046 1.664 5.702 3.590 3.75 4.059 1.725 5.731 3.632 3.79 4.130 1.776 5.814 3.722 3.86 4.232 1.864 6.048 3.788 3.98 4.293 1.925 6.185 3.874 4.07 4.387 2.098 6.361 4.048 4.22 4.488 2.166 6.577 4.100 4.33 4.763 2.238 6.869 4.252 4.53 5.006 2.384 6.988 4.420 4.70 5.194 2.560 7.207 4.608 4.89 5.344 2.587 7.337 4.804 5.02 5.506 2.672 7.529 5.032 5.18 5.597 2.782 7.729 5.188 5.32 5.693 2.838 7.884 5.352 5.44 5.742 2.869 8.100 5.420 5.53 5.842 2.960 8.217 5.510 5.63 6.122 3.056 8.334 5.646 5.79 6.157 3.131 8.496 5.700 5.87 6.176 3.146 8.674 5.836 5.96 6.198 3.157 8.726 5.900 6.00 6.213 3.168 8.748 5.946 6.02 6.235 3.224 8.748 6.000 6.05 6.250 3.272 8.748 6.000 6.07 6.301 3.341 8.975 6.072 6.17 6.358 3.434 9.104 6.260 6.29 6.584 3.462 9.446 6.362 6.46 6.795 3.486 9.756 6.532 6.64 6.912 3.550 9.992 6.730 6.80 6.998 3.640 10.177 6.890 6.93 SD (m l) 0.02 0.09 0.21 0.26 0.24 0.27 0.33 0.40 0.41 0.53 0.57 0.59 0.70 0.75 0.74 0.85 0.93 1.00 1.13 1.23 1.29 1.37 1.40 1.48 1.49 1.49 1.59 1.65 1.68 1.66 1.65 1.66 1.72 1.75 1.75 1.81 1.90 1.89 1.91 1.95 1.99 2.03 2.07 2.14 2.15 2.17 2.20 2.26 2.28 2.28 2.26 2.24 2.30 2.32 2.44 2.56 2.63 2.67 Page A35 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Tim e (hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 M eta bolic ca g e s gro u p 4 : H F + 0 .006 % P F H S A c c u m u la te d d rin k in take (m l) Average acc. c a g e 0 1 0 3 c a g e 0 1 0 7 c a g e 0 2 0 3 c a g e 02 0 7 drink intake (ml) 0.131 0.362 0 .2 1 4 0 .3 0 6 0.25 0.361 0.782 0 .8 8 0 0 .8 4 9 0.72 0 .4 7 9 0 .9 9 6 1.327 1.135 0.98 0 .5 7 4 1.207 1.512 1.254 1.14 0.612 1.207 1.718 1.395 1.23 0 .6 6 9 1.248 1.961 1.518 1.35 0 .7 6 8 1.343 1.995 1.558 1.42 0 .8 1 9 1.370 2 .0 8 5 1.606 1.47 0.982 1.377 2 .1 8 4 1.624 1.54 1.113 1.377 2 .1 8 4 1.694 1.59 1.121 1.550 2 .2 9 7 1.729 1.67 1.159 1.758 2 .3 1 0 1.815 1.76 1.290 1.880 2 .3 2 9 1.971 1.87 1.463 1.938 2 .5 2 0 2 .0 2 4 1.99 1.516 1.955 2 .5 4 5 2 .0 2 4 2.01 1.592 1.955 2 .7 4 7 2.081 2.09 1.615 1.955 2 .9 8 2 2.152 2.18 1.685 2.072 3 .1 3 7 2 .4 2 9 2.33 2 .0 4 8 2 .7 0 8 3 .6 2 0 2 .9 7 4 2.84 2 .3 2 9 2 .9 4 8 4 .0 5 3 3 .5 1 8 3.21 2 .4 5 3 3 .0 7 4 4 .5 7 4 3 .8 4 6 3.49 2.512 3 .1 8 6 4 .8 9 3 4.052 3.66 2 .5 4 6 3 .3 4 9 4 .9 9 8 4.092 3.75 2 .5 9 5 3.451 4 .9 9 8 4 .1 4 5 3.80 2 .6 4 5 3.461 5 .0 9 3 4.312 3.88 2 .6 8 3 3.667 5 .1 8 7 4.312 3.96 2.831 3 .8 5 6 5.271 4 .3 9 6 4.09 2 .9 4 5 3 .9 1 0 5 .4 1 4 4 .5 7 6 4.21 3.027 4 .1 7 5 5 .5 2 7 4 .7 0 8 4.36 3 .1 7 3 4.352 5 .5 6 5 4.717 4.45 3.192 4.352 5 .6 4 9 4.752 4.49 3.211 4 .4 2 3 5 .7 1 2 4 .7 5 9 4.53 3 .2 7 6 4 .4 9 8 5 .9 4 3 4 .8 8 8 4.65 3 .4 1 6 4.651 6 .2 0 3 4 .9 5 0 4.81 3 .5 8 5 4 .7 6 3 6 .4 2 2 4 .9 5 0 4.93 3 .7 5 3 4 .8 5 9 6 .7 6 6 5 .0 2 5 5.10 4.051 5 .0 0 5 7 .0 4 6 5 .3 5 0 5.36 4 .3 6 6 5 .2 6 3 7 .3 8 8 5 .8 7 0 5.72 4 .5 7 9 5.632 7 .6 4 2 6 .3 9 5 6.06 4 .5 7 9 5 .7 9 4 7 .8 5 4 6 .7 4 3 6.24 4 .5 7 9 5 .8 6 8 7 .8 9 2 7 .0 1 8 6.34 4 .5 7 9 5 .9 3 0 8 .1 0 0 7.227 6.46 4 .6 9 9 6.011 8 .2 4 5 7 .4 5 4 6.60 4 .8 0 3 6.042 8 .3 9 2 7 .6 0 8 6.71 4.872 6 .1 0 6 8 .6 1 0 7 .7 2 6 6.83 4 .9 4 0 6 .1 8 8 8 .7 3 6 7 .8 0 6 6.92 4 .9 7 8 6.297 8 .7 3 6 7 .8 5 4 6.97 5 .0 4 3 6.351 8 .7 3 6 7 .9 2 0 7.01 5 .0 8 8 6 .4 5 0 8 .7 6 3 8 .0 0 4 7.08 5.111 6 .4 6 0 8 .9 0 4 8 .0 7 4 7.14 5.111 6 .5 0 4 8 .9 8 8 8 .1 4 0 7.19 5.172 6.542 9 .1 1 4 8 .1 7 5 7.25 5.187 6 .6 6 4 9 .2 8 4 8 .2 2 8 7.34 5 .3 2 4 6 .7 2 5 9 .3 0 3 8.391 7.44 5 .5 9 6 6.732 9 .5 7 4 8.532 7.61 5.917 6 .7 7 3 9.811 8 .7 0 8 7.80 6 .2 3 6 6 .9 4 3 10.019 9.082 8.07 6 .3 3 5 7 .1 3 3 10.185 9.297 8.24 SD (ml) 0.10 0.24 0.36 0.40 0.46 0.54 0.51 0.53 0.50 0.46 0.49 0.47 0.43 0.43 0.42 0.48 0.58 0.62 0.65 0.74 0.92 1.04 1.05 1.02 1.06 1.06 1.02 1.04 1.05 0.99 1.02 1.03 1.10 1.14 1.16 1.25 1.25 1.27 1.29 1.39 1.44 1.54 1.57 1.60 1.67 1.69 1.67 1.64 1.64 1.69 1.73 1.75 1.79 1.77 1.78 1.78 1.78 1.80 Tim e (hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 3 9 .9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 5 2 .4 5 3 .6 5 4 .9 56.1 5 7 .4 5 8 .6 5 9 .9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 M eta bolic ca g e s gro u p 6 H F + 0 .003 % P F O S A ccu m ulated d rin k intake (m l) I Average acc. c a g e 0 1 0 4 c a g e 0 1 0 8 c a g e 0 2 0 4 c a g e 0 2 0 8 drink intake (ml) 0 .1 3 4 0 .2 4 0 0.151 0.202 0.18 0.711 0 .2 8 8 0 .7 2 4 0 .4 7 0 0.55 1.078 0 .3 2 8 1.159 0 .6 1 6 0.80 1.282 0 .5 6 3 1.269 0 .7 1 6 0.96 1.576 0 .8 1 3 1.505 0 .8 4 0 1.18 1.877 0 .8 8 3 1.667 0 .9 7 6 1.35 2 .1 7 9 0 .8 9 6 1.818 1.062 1.49 2 .3 9 4 0.941 1.957 1.100 1.60 2.567 0 .9 9 2 2 .0 1 6 1.216 1.70 2 .6 6 9 1.085 2 .0 1 6 1.280 1.76 2 .8 2 0 1.146 2 .0 1 6 1.288 1.82 2 .9 4 8 1.253 2 .0 1 6 1.360 1.89 2.992 1.264 2 .0 1 6 1.422 1.92 2.992 1.278 2 .0 1 6 1.446 1.93 3.012 1.312 2 .0 1 6 1.560 1.98 3.135 1.312 2 .0 8 8 1.576 2.03 3 .1 9 6 1.338 2 .1 6 0 1.630 2.08 3 .3 4 4 1.506 2 .1 9 8 1.794 2.21 3.611 1.768 2.362 2.022 2.44 3.822 2 .0 9 3 2.907 2 .1 9 8 2.75 4 .0 3 9 2 .1 9 8 3 .3 0 8 2 .3 9 0 2.98 4.097 2 .3 1 7 3 .4 3 8 2 .5 3 4 3.10 4.097 2 .3 9 4 3 .6 2 0 2 .6 6 4 3.19 4.097 2 .5 5 7 3 .9 7 8 2 .8 0 8 3.36 4.097 2 .6 4 2 4 .1 0 4 2 .9 4 0 3.45 4 .1 4 8 2 .7 2 0 4.111 3 .0 0 0 3.49 4 .4 2 3 2 .7 7 4 4 .1 7 6 3 .1 3 4 3.63 4 .6 4 8 2 .8 3 2 4 .3 6 3 3.342 3.80 4 .7 8 4 2 .8 6 4 4.437 3 .4 6 8 3.89 4 .9 4 4 2 .9 0 2 4 .4 6 4 3 .4 8 0 3.95 5 .1 1 7 3 .0 2 4 4 .5 2 9 3 .4 9 4 4.04 5.151 3 .0 2 4 4 .6 9 8 3 .5 0 6 4.09 5 .1 5 6 3 .0 4 6 4 .6 9 8 3 .5 5 0 4.11 5 .2 0 2 3 .1 7 8 4 .6 9 8 3 .6 3 6 4.18 5 .2 6 3 3 .2 0 5 4 .6 9 8 3.732 4.22 5 .5 3 5 3 .3 3 4 4 .8 0 6 3 .8 5 8 4.38 5 .8 7 9 3 .6 2 4 5 .1 2 3 3 .9 7 4 4.65 5 .9 6 4 3 .8 9 8 5.377 4 .1 4 8 4.85 6.137 4 .2 4 2 5 .5 5 5 4 .3 7 8 5.08 6.392 4 .3 4 6 5.767 4 .5 6 0 5.27 6.681 4 .5 3 6 5 .9 9 4 4 .6 7 6 5.47 6.871 4 .6 0 8 6 .1 1 8 4 .7 7 8 5.59 6 .9 8 9 4 .7 0 7 6.311 4 .9 5 8 5.74 7.342 4.891 6 .3 9 0 5 .0 2 0 5.91 7.431 4 .9 1 2 6 .6 0 4 5 .2 1 2 6.04 7.497 5 .0 2 2 6.772 5 .3 4 6 6.16 7 .6 1 6 5 .1 5 2 6 .8 0 4 5 .4 5 2 6.26 7 .6 1 6 5 .1 6 8 6 .8 0 4 5 .5 1 6 6.28 7 .6 1 6 5 .2 1 6 6 .8 0 4 5 .5 4 0 6.29 7 .6 5 9 5 .2 2 2 6 .8 0 4 5 .5 4 0 6.31 7.701 5 .2 3 2 6 .8 0 4 5 .5 4 0 6.32 7.701 5 .2 9 0 6 .8 0 4 5 .5 6 8 6.34 7.701 5 .3 4 7 6 .8 0 4 5 .6 3 0 6.37 7.701 5 .4 0 8 6 .8 0 4 5 .6 7 6 6.40 7 .8 1 3 5 .5 0 4 6 .9 4 4 5 .8 2 4 6.52 8 .0 5 0 5 .6 7 8 7 .1 7 5 5 .9 5 2 6.71 8 .1 0 9 5 .9 8 7 7.547 6 .0 9 8 6.94 8 .1 0 9 6 .2 4 2 7 .6 8 6 6 .3 0 4 7.09 SD (ml) 0.05 0.21 0.39 0.37 0.41 0.50 0.61 0.69 0.73 0.73 0.77 0.78 0.78 0.77 0.75 0.81 0.82 0.81 0.82 0.80 0.85 0.83 0.80 0.79 0.77 0.74 0.80 0.85 0.88 0.93 0.95 1.00 0.98 0.93 0.93 0.98 1.04 0.99 0.92 0.98 1.04 1.09 1.09 1.17 1.18 1.17 1.16 1.14 1.12 1.13 1.15 1.12 1.09 1.06 1.06 1.10 1.06 0.95 Page A36 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 T im e (h r) 6 .1 7 .4 8 .6 9 .9 1 1 .1 1 2 .4 1 3 .6 1 4 .9 1 6 .1 1 7 .4 1 8 .6 1 9 .9 2 1 .1 2 2 .4 2 3 .6 2 4 .9 2 6 .1 2 7 .4 2 8 .6 2 9 .9 3 1 .1 3 2 .4 3 3 .6 3 4 .9 3 6 .1 3 7 .4 3 8 .6 3 9 .9 4 1 .1 4 2 .4 4 3 .6 4 4 .9 4 6 .1 4 7 .4 4 8 .6 4 9 .9 5 1 .1 5 2 .4 5 3 .6 5 4 .9 5 6 .1 5 7 .4 5 8 .6 5 9 .9 6 1 .1 6 2 .4 6 3 .6 6 4 .9 6 6 .1 6 7 .4 6 8 .6 6 9 .9 7 1 .1 7 2 .4 7 3 .6 7 4 .9 7 6 .1 7 7 .4 group 1 v s 3 nn 44 p 0 .3 4 3 44 0 .3 4 3 44 44 44 44 0 .4 8 6 0 .6 8 6 0 .8 8 6 0 .6 8 6 44 44 44 44 44 0 .4 8 6 0 .6 8 6 0 .8 8 6 0 .8 8 6 0 .8 8 6 44 44 44 44 44 44 44 0 .8 6 0 0 .8 8 6 1 .0 0 0 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .8 8 6 44 0 .4 8 6 44 0 .3 4 3 44 44 44 44 0 .4 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 44 0 .3 4 3 44 0 .3 4 3 44 0 .4 8 6 44 0 .4 8 6 44 0 .4 8 6 44 0 .4 8 6 44 0 .4 8 6 44 0 .4 8 6 44 0 .4 8 6 44 0 .3 4 3 44 0 .3 4 3 44 0 .3 4 3 44 0 .4 8 6 44 0 .4 8 6 44 0 .4 8 6 44 0 .4 8 6 44 0 .4 8 6 44 0 .4 8 6 44 0 .4 8 6 44 0 .4 8 6 44 44 44 44 44 44 44 0 .4 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 44 0 .4 8 6 44 0 .4 8 6 44 0 .4 8 6 44 0 .4 8 6 44 0 .4 8 6 44 0 .4 8 6 44 0. 3 4 3 Accumulated drink intake; p-values Mann Whitney U-test group vsg r o u p 1 v s 4 g r o u p 1 v s 6 g r o u p 3 v s 4 g r o u p 3 v s 6 46 nn p nn 4 4 I 0 .3 4 3 I 4 4 4 4 0 .2 0 0 4 4 4 4 0 .3 4 3 4 4 4 4 0 .3 4 3 4 4 4 4 0 .4 8 6 4 4 4 4 0 .6 8 6 4 4 4 4 0 .6 8 6 4 4 4 4 0 .6 8 6 4 4 4 4 0 .8 8 6 4 4 4 4 0 .8 8 6 4 4 44 qqrrmm LL4 4 4 4 0 686 4 4 4 4 0 .4 8 6 4 4 4 4 0 .8 8 6 4 4 4 4 0 .8 8 6 4 4 4 4 1 .0 0 0 4 4 4 qrm L 4 4 4 0 343 4 4 4 4 0 486 4 4 4 4 0 486 4 4 4 4 0 .4 8 6 4 4 4 4 0 .4 8 6 4 4 4 4 0 .4 8 6 4 4 4 4 0 .6 8 6 4 4 4 4 0 686 4 4 4 4 0 686 4 4 4 4 0 686 4 4 4 4 0 .6 8 6 4 4 4 4 0 .6 8 6 4 4 4 4 0 .6 8 6 4 4 4 4 0 .6 8 6 4 4 4 4 0 686 4 4 4 4 0 886 4 4 4 qrm L 4 4 4 0 886 4 4 4 4 0 .8 8 6 4 4 4 4 0 .6 8 6 4 4 4 4 0 .4 8 6 4 4 4 4 0 .4 8 6 4 4 4 4 0 486 4 4 4 4 0 486 4 4 4 4 0 .6 8 6 4 4 4 4 0 .8 8 6 4 4 4 4 0 .8 8 6 4 4 4 4 0 .8 8 6 4 4 4 4 0 .8 8 6 4 4 4 4 0 886 4 4 4 4 0 .8 8 6 4 4 4 4 0 886 4 4 4 4 0 886 4 4 4 4 0 .8 8 6 4 4 4 4 0 .8 8 6 4 4 4 4 0 .8 8 6 4 4 4 4 0 .8 8 6 4 4 4 4 0 886 4 4 4 4 0 886 4 4 4 I" 4 I 0 . 8 8 6 | 4 | 4 0 .6 8 6 0 .8 8 6 1 .0 0 0 1 .0 0 0 0 .6 8 6 0 .8 8 6 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 0 .8 8 6 0 .8 8 6 0 .8 8 6 0 .6 8 6 0 .8 8 6 0 .8 8 6 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 0 .8 8 6 0 .6 8 6 0 .6 8 6 0 .8 8 6 0 .8 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .4 8 6 0 .6 8 6 0 .8 8 6 0 .8 8 6 0 .8 8 6 0 .8 8 6 0 .8 8 6 0 .8 8 6 0 .8 8 6 0 .8 8 6 0 .8 8 6 0 .8 8 6 0 .8 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .4 8 6 0 .4 8 6 0 .3 4 3 0 .3 4 3 0 .4 8 6 0 .3 4 3 0 .3 4 3 0 .0 2 9 0 .3 4 3 0 .3 4 3 0 .2 0 0 0 .4 8 6 0 .4 8 6 0 .6 8 6 0 .8 8 6 0 .8 8 6 0 .8 8 6 0 .6 8 6 0 .4 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .8 8 6 0 .8 8 6 0 .6 8 6 0 .6 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .6 8 6 0 .4 8 6 0 .4 8 6 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 0 .0 2 9 0 .4 8 6 0 .6 8 6 0 .4 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .8 8 6 0 .8 8 6 0 .8 8 6 0 .8 8 6 0 .8 8 6 0 .8 8 6 0 .8 8 6 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 1 .0 0 0 nn 0 .3 4 3 0 .2 0 0 0 .6 8 6 0 .8 8 6 1 .0 0 0 1 .0 0 0 0 .8 8 6 0 .8 8 6 0 .8 8 6 1 .0 0 0 0 .8 8 6 0 .8 8 6 1 .0 0 0 0 .6 8 6 0 .8 8 6 0 .8 8 6 1 .0 0 0 0 .8 8 6 0 .3 4 3 0 .3 4 3 0 .4 8 6 0 .6 8 6 0 .6 8 6 0 .4 8 6 p< 0 .0 5 0 .4 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .4 8 6 0 .2 0 0 0 .2 0 0 0 .4 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .6 8 6 0 .4 8 6 0 .4 8 6 0 .3 4 3 0 .3 4 3 age 3 / of A 1 72 Appendix to TNO-report of 3M-02 Final version 04-12-2006 D4. X activity measurements Tim e (hr) 6.1 7.4 8 .6 9 .9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 Metabolic cages group 1 : H F control X activity per interval A verag e cage 0101 cage 0105 cage 0201 cage 0205 X activity 100.7 88.8 134.7 99.5 105.9 63.9 227.7 123.3 73.9 122.2 67.5 124.2 57.2 69.0 79.5 76.1 238.3 182.4 62.8 139.9 90.7 71.1 72.9 173.1 102.0 88.6 74.3 128.0 80.4 92.8 69.1 109.8 54.7 35.5 67.3 72.2 28.9 67.7 67.7 59.1 14.3 92.9 70.7 46.6 56.1 112.4 64.9 119.1 63.5 90.0 144.9 81.0 41.1 47.5 78.6 74.2 81.1 92.5 166.7 103.6 44.1 99.0 49.7 29.3 55.5 47.4 71.0 121.8 94.7 83.7 88.3 91.9 108.7 57.4 86.6 424.8 330.7 375.7 615.8 436.8 133.7 276.6 421.4 814.9 411.7 331.4 346.2 385.6 228.3 322.9 121.9 221.1 257.7 488.8 272.4 143.4 139.3 121.1 158.0 140.5 133.1 229.4 213.0 217.7 198.3 74.2 181.4 129.7 250.7 159.0 54.6 182.5 199.9 94.7 132.9 172.7 166.9 158.2 119.2 154.3 84.7 128.2 53.6 109.3 94.0 101.7 122.5 136.4 118.5 119.8 53.4 25.2 67.8 54.2 50.2 33.9 49.9 56.4 55.9 49.0 84.9 47.7 44.7 23.0 50.1 28.9 79.6 74.6 119.0 75.5 64.8 34.9 59.5 96.2 63.9 74.9 64.0 65.7 38.0 60.7 69.8 101.4 87.1 72.6 82.7 90.4 52.7 46.1 71.2 65.1 373.3 279.0 284.9 313.7 312.7 337.7 147.0 370.8 371.0 306.6 361.6 270.6 276.3 229.2 284.4 161.5 365.6 199.2 227.9 238.6 164.7 143.5 156.8 202.0 166.8 119.6 206.4 153.3 185.1 166.1 76.2 117.9 136.6 57.6 97.1 82.3 180.9 143.9 106.5 128.4 96.9 97.8 154.2 234.6 145.9 173.9 144.2 96.5 86.3 125.2 90.2 68.3 85.5 90.4 83.6 71.4 80.6 87.9 29.3 67.3 49.0 185.5 93.7 91.4 104.9 94.4 67.4 115.8 76.0 88.4 36.2 14.6 23.2 57.4 32.9 91.6 118.8 97.4 31.4 84.8 42.5 77.5 37.2 106.7 66.0 50.0 112.7 53.7 40.3 64.2 94.0 43.9 83.9 120.3 85.5 186.7 126.5 215.6 235.7 191.1 380.3 349.8 374.6 551.9 414.2 411.4 223.4 274.0 372.4 320.3 246.9 230.0 248.0 185.3 227.6 156.4 360.5 270.5 260.9 262.1 SD 19.9 75.0 30.3 84.7 48.3 24.2 31.5 20.3 33.7 29.9 4 7 .5 42.7 30.2 31.9 21.4 125.4 293.4 67.1 155.3 15.2 44.0 75.2 69.6 24.1 32.3 14.3 17.9 10.5 25.7 36.9 25.2 15.8 14.6 19.9 43.1 107.6 55.6 89.0 25.1 37.9 36.5 43.2 64.9 41.1 10.4 26.2 57.5 21.5 18.6 37.5 32.5 32.8 31.7 4 7 .5 92.8 86.7 29.3 83.5 Tim e (hr) 6.1 7.4 8 .6 9 .9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 M etabolic cages group 3: H F + 0 .0 3 % PFBS X activity per interval Average cage 0102 cage 0 106 cage 0202 cage 0206 X activity 92.2 254.5 88.7 185.0 155.1 9 2 .7 238.4 92.6 375.7 199.9 79.1 99.1 110.4 111.4 100.0 131.6 82.0 45.9 221.7 120.3 134.8 124.3 259.8 60.1 144.8 5 4 .7 138.5 174.2 39.8 101.8 134.4 53.3 68.6 182.7 109.8 5 9 .0 82.5 103.6 47.8 73.2 122.4 105.6 146.3 18.4 98.2 8 4 .7 29.6 245.5 93.8 113.4 158.6 172.4 76.4 41.6 112.3 2 1 .0 39.6 50.1 14.5 31.3 9 3 .0 113.8 169.7 118.6 123.8 111.5 160.0 89.9 126.0 121.9 158.6 55.4 169.7 72.4 114.0 454.8 579.9 431.8 455.2 480.4 432.8 621.4 618.1 933.4 651.4 277.4 351.9 422.6 616.8 417.2 325.6 48.8 191.6 130.5 174.1 262.1 373.9 151.6 282.2 267.5 9 5 .4 52.6 238.0 216.4 150.6 127.8 215.5 260.5 148.1 188.0 9 9 .6 135.3 127.1 112.9 118.7 199.2 141.3 217.7 267.4 206.4 135.8 276.8 172.6 73.8 164.8 109.4 98.3 200.9 103.7 128.1 5 8 .6 61.8 132.5 28.6 70.4 6 1 .9 88.5 155.1 26.9 83.1 6 0 .3 164.0 35.5 11.7 67.9 4 7 .7 32.8 87.4 223.3 97.8 69.2 57.8 71.1 68.3 66.6 131.2 97.6 173.2 60.2 115.6 8 8 .0 78.5 143.7 50.2 90.1 120.8 63.9 104.5 30.4 79.9 361.3 203.4 323.6 485.2 343.4 527.6 382.4 442.4 1 1 9 4 .3 636.7 308.7 470.4 298.9 609.6 421.9 201.9 177.0 84.2 327.0 197.5 332.9 80.5 218.2 274.2 226.5 117.4 102.8 219.6 242.1 170.5 136.8 300.6 165.3 167.6 192.6 121.2 113.3 113.2 309.0 164.2 177.5 352.3 305.4 374.6 302.5 236.1 139.3 186.5 212.9 193.7 70.6 171.6 92.8 28.1 90.8 102.9 131.2 71.9 161.7 116.9 72.1 72.4 43.7 9.3 49.4 6 2 .0 63.4 125.6 266.9 129.5 130.8 49.7 53.5 23.2 64.3 75.2 27.2 84.9 221.5 102.2 8 4 .0 116.4 51.9 45.1 74.4 63.1 82.3 73.4 35.7 63.6 129.7 62.8 151.3 92.7 109.1 201.6 143.3 125.5 219.4 172.5 429.8 396.0 387.1 405.0 404.5 278.5 493.7 280.0 701.6 438.5 270.4 175.4 217.9 407.2 267.7 256.5 298.8 295.6 603.1 363.5 SD 79.9 135.9 15.0 76.2 83.5 64.9 60.0 24.9 55.7 92.5 63.4 16.4 32.6 29.4 58.5 67.2 207.6 145.7 116.7 91.3 90.6 61.2 15.8 52.1 85.1 48.8 44.0 54.2 67.1 86.8 6.0 48.1 39.2 40.8 116.1 376.5 147.8 100.1 108.0 70.6 73.4 96.6 88.2 41.5 60.2 38.4 29.9 96.3 46.3 83.4 32.8 20.2 39.2 45.1 18.4 202.5 100.8 160.9 Page A38 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Time (hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 Metabolic cages group 4: HF + 0.006 % PFHS X activity per interval Average cage 0103 cage 0107 cage 0203 cage 0207 X activity 75.4 118.1 92.7 258.6 136.2 91.1 61.6 100.7 151.8 101.3 32.3 128.9 85.4 124.6 92.8 88.7 58.6 66.1 53.7 66.8 56.0 47.9 89.9 144.3 84.5 79.3 139.0 66.9 185.7 117.7 103.8 31.0 43.1 57.7 58.9 51.9 53.5 153.0 95.1 88.4 65.2 199.5 53.3 90.9 102.2 83.7 172.4 74.7 34.6 91.4 28.4 46.4 42.0 124.4 60.3 59.3 94.9 103.2 76.9 83.6 108.0 72.6 51.6 57.3 72.4 59.8 39.3 122.1 273.1 123.6 71.2 76.4 74.7 95.4 79.4 484.3 589.1 168.2 410.3 413.0 821.1 605.3 368.9 719.7 628.8 418.6 371.6 219.7 566.0 394.0 282.1 99.3 260.1 379.5 255.3 175.2 215.2 227.2 177.6 198.8 203.6 190.6 144.7 107.9 161.7 92.2 84.7 83.6 169.4 107.5 146.6 178.0 157.2 185.6 166.9 85.3 14.1 101.8 125.7 81.7 173.4 94.0 82.6 336.9 171.7 141.5 111.9 103.3 374.0 182.7 97.6 65.8 82.8 63.6 77.5 46.4 28.1 47.1 140.5 65.5 54.7 69.4 73.6 65.1 65.7 47.0 47.6 44.3 73.3 53.1 79.7 55.9 49.8 76.8 65.6 33.1 77.6 137.3 47.2 73.8 141.3 169.8 67.1 187.9 141.5 148.8 21.7 77.9 55.3 75.9 211.0 139.5 118.3 271.5 185.1 555.2 277.4 176.1 489.8 374.6 227.0 219.5 308.1 548.7 325.8 192.2 120.1 214.5 482.5 252.3 145.5 229.0 129.1 229.2 183.2 159.5 85.7 211.4 146.7 150.8 114.2 96.2 119.5 189.7 129.9 64.4 84.0 123.6 69.4 85.4 116.3 161.9 141.4 211.7 157.8 59.8 24.8 79.1 127.3 72.8 98.7 39.5 90.8 97.0 81.5 97.6 87.9 60.4 116.3 90.6 97.9 39.2 108.8 93.5 84.9 87.3 120.3 55.8 55.3 79.7 69.4 44.1 120.1 211.5 111.3 63.4 28.1 69.2 83.9 61.2 34.3 79.2 92.1 126.5 83.0 77.4 110.7 103.2 151.6 110.7 54.9 103.1 77.5 66.3 75.5 121.3 183.4 84.3 76.1 116.3 262.2 613.3 156.4 233.3 316.3 393.8 463.2 326.7 686.7 467.6 152.2 146.0 423.4 234.1 238.9 160.4 290.0 246.2 300.4 249.3 SD 83.5 37.6 44.8 15.5 43.8 55.2 31.9 47.5 66.7 58.1 43.4 19.6 25.4 105.7 10.9 178.9 194.4 142.7 116.2 26.3 43.9 41.5 18.1 48.0 117.3 128.6 15.9 50.8 8.1 13.6 14.9 46.2 53.2 53.8 69.9 177.7 153.9 158.7 53.4 51.6 41.1 26.8 40.5 42.8 28.2 23.3 31.1 30.9 73.9 23.7 38.1 30.8 20.6 48.9 203.0 156.3 129.4 63.7 Time (hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 Metabolic cages group 6 HF + 0.003 % PFOS X activity per interval | Average cage 0104 cage 0108 cage 0204 cage 0208 X activity 152.1 223.2 114.3 130.4 155.0 136.3 217.5 107.7 211.5 168.3 37.5 132.4 78.6 35.1 70.9 120.1 164.6 61.9 77.3 106.0 165.9 124.0 96.1 64.6 112.7 64.9 56.9 76.3 42.0 60.0 99.3 51.5 54.9 136.8 85.6 66.3 168.5 118.2 51.8 101.2 35.2 74.0 67.3 72.4 62.2 29.9 94.3 55.5 23.5 50.8 75.5 152.4 123.9 48.4 100.1 94.7 30.6 41.5 67.2 58.5 61.8 90.8 77.4 96.6 81.7 41.2 176.7 52.9 68.4 84.8 154.0 98.7 119.9 115.8 122.1 248.5 353.9 134.8 128.7 216.5 432.4 353.1 703.1 283.1 442.9 225.6 313.2 437.8 367.4 336.0 250.2 403.1 203.5 248.2 276.3 130.8 117.3 152.3 164.3 141.2 194.5 243.2 125.1 138.7 175.4 136.1 54.8 78.9 156.4 106.6 138.1 137.0 183.6 133.4 148.0 250.1 184.4 140.2 133.4 177.0 164.8 39.0 140.4 63.1 101.8 111.8 88.9 133.9 108.8 110.9 81.0 99.0 41.5 98.2 79.9 64.7 12.4 52.8 123.7 63.4 29.8 48.0 55.2 50.8 46.0 36.2 141.9 24.8 28.7 57.9 73.6 35.9 147.9 112.9 92.6 75.9 45.5 63.5 32.1 54.3 42.3 63.0 57.3 78.0 60.2 38.4 84.7 46.8 106.0 69.0 140.0 152.0 217.4 78.4 147.0 405.1 292.8 232.2 226.6 289.2 131.5 332.3 228.9 252.9 236.4 212.6 410.7 208.7 235.1 266.8 114.7 310.1 107.5 227.4 189.9 136.0 161.8 93.3 83.1 118.6 198.1 73.7 158.3 108.8 134.7 89.1 134.6 91.5 166.0 120.3 136.5 126.4 110.9 175.2 137.3 180.5 105.8 129.4 141.3 139.3 85.9 71.5 90.4 116.7 91.1 56.8 151.5 70.7 107.5 96.6 74.8 40.4 70.0 67.5 63.2 42.2 130.3 32.1 72.8 69.4 26.7 24.3 85.4 91.4 57.0 74.5 80.0 53.0 61.2 67.2 59.1 27.3 68.7 34.4 47.4 57.3 101.8 40.5 102.7 75.6 55.0 80.3 57.9 55.6 62.2 106.5 43.9 112.9 98.0 90.3 193.8 308.6 110.3 109.8 180.6 256.2 142.5 208.6 290.9 224.6 131.1 305.9 223.4 367.3 256.9 203.7 407.8 178.4 337.2 281.8 SD 48.0 54.7 45.6 46.2 43.0 14.4 40.5 53.2 18.2 32.1 46.8 28.6 15.5 62.3 23.2 106.9 183.9 89.5 87.3 21.1 54.3 47.6 23.8 53.7 60.3 18.4 26.9 46.0 11.2 56.2 48.5 19.3 14.8 31.9 57.0 82.9 82.7 96.7 97.1 36.8 54.7 36.9 27.4 31.2 18.9 42.4 15.5 44.2 36.4 12.3 19.7 31.6 12.1 31.5 94.0 64.3 102.5 109.1 Page A39 of A172 Appendix to TNO-report of 3M-02_____________ Final version 04-12-2006 Time ( hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 group 1 vs 3 nn p 4 4 0.886 4 4 0.343 4 4 0.343 4 4 0.886 4 4 0.686 4 4 1.000 4 4 0.486 4 4 0.686 4 4 0.200 4 4 1.000 4 4 0.486 4 4 0.029 4 4 0.057 4 4 0.200 4 4 0.886 4 4 0.343 4 4 0.200 4 4 0.343 4 4 0.486 4 4 0.057 4 4 0.686 4 4 0.686 4 4 1.000 4 4 0.200 4 4 0.200 4 4 0.686 4 4 0.486 4 4 0.343 4 4 1.000 4 4 0.886 4 4 0.686 4 4 0.200 4 4 0.886 4 4 0.684 4 4 0.686 4 4 0.029 4 4 0.114 4 4 0.686 4 4 0.343 4 4 1.000 4 4 0.029 4 4 0.686 4 4 0.057 4 4 0.114 4 4 0.886 4 4 0.114 4 4 0.114 4 4 1.000 4 4 0.343 4 4 0.686 4 4 0.486 4 4 0.886 4 4 0.486 4 4 0.686 4 4 0.343 4 4 0.343 4 4 0.886 4 4 0.486 X activity; p-values Mann Whitney U-test group 1 vs 4 group 1 vs 6 | group 3 vs 4 group 3 vs 6 n n p n [Q p n 4 4 | 1.000 I 4 4 0.114 4 1.000 4 0.886 4 4 0.886 4 4 0.486 4 0.343 4 1.000 4 4 0.486 4 4 0.886 4 0.886 4 0.343 4 4 0.200 4 4 0.686 4 0.486 4 0.886 4 4 0.486 4 4 0.886 4 0.343 4 0.686 4 4 0.886 4 4 0.057 4 0.486 4 0.886 4 4 0.686 4 4 0.686 4 0.200 4 0.686 4 4 0.686 4 4 0.686 4 0.886 4 0.486 4 4 0.486 4 4 0.886 4 0.886 4 0.343 4 4 1.000 4 4 0.114 4 4 4 0.48m 4 4 0.486 4 4 4 0.88m 4 4 0.200 4 0.686 4 0.343 4 0.029 4 0.486 0.686 0.200 4 4 0.20m 4 4 0.343 4 0.057 4 0.057 4 4 0.88m 4 4 0.686 4 4 4 0.68m 4 4 0.057 4 0.686 4 0.886 4 0.343 1.000 4 4 1.00m 4 4 0.057 4 0.886 4 0.029 4 4 0.34m 4 4 0.686 4 4 4 0.48m 4 4 1.000 4 0.886 4 0.886 4 0.200 0.686 4 4 0.88m 4 4 1.000 4 0.486 4 0.200 4 4 I 2 9 4 4 1.000 4 4 4 0.20m 4 4 0.686 4 0.343 4 1.000 4 0.114 0.686 4 4 0.48m 4 4 0.486 4 4 4 0.88m 4 4 0.886 4 0.114 4 0.029 4 0.200 0.057 4 4 0.05m 4 4 0.686 4 0.029 4 0.343 4 4 0.486 4 4 0.886 4 0.886 4 0.343 4 4 0.68m 4 4 0.486 4 0.486 4 1.000 4 4 0.114 4 4 0.200 4 4 4 0.68m 4 4 0.686 4 0.343 4 0.686 4 0.686 0.686 4 4 0.34m 4 4 0.686 4 0.486 4 0.886 4 4 0.34m 4 4 0.486 4 0.486 4 0.343 4 4 1.00m 4 4 0.343 4 1.000 4 0.343 4 4 0.88m 4 4 0.686 4 4 4 0.34m 4 4 0.114 4 0.343 4 0.343 4 0.114 0.200 4 4 0.886 4 4 1.000 4 0.886 4 0.886 4 4 10 0 2 9 4 4 0.029 4 4 4 0.68m 4 4 0.886 4 0.114 4 0.486 4 0.057 0.057 4 4 0.88m 4 4 0.343 4 4 4 0.88m 4 4 0.486 4 0.343 4 0.686 4 0.114 0.200 4 4 0.886 4 4 1.000 4 0.686 4 0.886 4 4 0.88m 4 4 0.200 4 0.686 4 0.343 4 4 0.48m 4 4 0.486 4 0.200 4 0.343 4 4 0.20m 4 4 0.886 4 0.200 4 0.686 4 4 0.68m 4 4 0.886 4 0.057 4 0.029 4 4 0.114 4 4 0.686 4 4 4 0.34m 4 4 0.486 4 0.029 4 0.886 4 0.114 0.886 4 4 0.20m 4 4 0.686 4 0.343 4 0.486 4 4 1.00m 4 4 0.200 4 0.200 4 0.886 4 4 | 0.686 | 4 4 0.486 4 0.343 4 0.486 4 4 0.05m 4 4 0.343 4 0.486 4 1.000 4 4 0.20m 4 4 0.343 4 0.486 4 0.486 4 4 0.68m 4 4 0.343 4 0.886 4 0.343 4 4 0.20m 4 4 0.686 4 0.057 4 0.686 4 4 | 0.68m 4 4 0.343 4 0.343 4 0.057 4 4 0.057 4 4 0.029 4 0.114 4 0.029 4 4 0.34m 4 4 0.029 4 0.343 4 0.029 4 4 0.20m 4 4 0.200 4 4 4 0.68m 4 4 0.886 4 m4 4 \ 1.00 4 4 0.886 4 0.886 4 0.686 4 0.343 4 0.114 1.000 0.686 group 4 vs 6 0.486 0.114 0.886 0.200 0.343 0.057 0.486 0.886 0.686 0.343 0.200 0.200 0.486 0.886 0.029 0.114 0.200 0.686 0.886 0.029 0.886 0.686 0.200 0.029 0.343 0.343 0.686 0.886 0.057 0.343 0.686 0.486 0.057 1.000 0.886 0.686 0.886 0.686 0.686 0.486 1.000 0.114 0.486 0.057 0.886 1.000 0.343 0.686 0.343 1.000 0.200 0.114 0.686 0.686 0.343 0.029 1.000 0.686 I I p<005 I Page A40 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 D5. O2 consumption,CO2 production and respiratory exchange ratio measurements O2 consumption T im e (h r) 6.1 7 .4 8.6 9.9 11.1 1 2 .4 13.6 14.9 16.1 1 7 .4 18.6 19.9 21.1 2 2 .4 2 3 .6 2 4 .9 26.1 2 7 .4 2 8 .6 2 9 .9 31.1 3 2 .4 3 3 .6 3 4 .9 36.1 3 7 .4 3 8 .6 3 9 .9 41.1 4 2 .4 4 3 .6 4 4 .9 46.1 4 7 .4 4 8 .6 4 9 .9 51.1 5 2 .4 5 3 .6 5 4 .9 56.1 5 7 .4 5 8 .6 5 9 .9 61.1 6 2 .4 6 3 .6 6 4 .9 66.1 6 7 .4 6 8 .6 6 9 .9 71.1 7 2 .4 7 3 .6 7 4 .9 76.1 7 7 .4 M e ta b o lic c a g e s g ro u p 1 : H F c o n t rol V O 2 (m l/h/kg m ouse) Average VO2 cage 0101 cage 0105 cage 0201 cage 0205 3055 3609 3572 3183 2909 3769 3278 2987 2786 3499 3070 3028 3051 3540 3607 2913 2741 3200 2943 3204 2814 2966 3194 2903 2636 3102 2744 2661 2685 2756 2766 2705 2399 2814 2770 2676 2811 2699 2874 2756 3115 2850 2610 2730 2766 2917 2939 3098 2602 2990 2628 2542 2743 2708 2828 2892 3001 2983 2979 2785 3803 3693 3803 3939 2959 3356 3539 3857 3391 3518 3497 3027 2921 3300 3385 3544 2968 3266 3115 2992 2981 3263 3316 3042 2763 3180 3307 3199 2742 3182 3401 2921 3160 3090 3203 2842 2844 3097 2702 2680 2831 2938 3274 2716 2671 2564 2826 2528 2400 2696 2776 2658 2690 2672 2630 2450 2344 2796 2790 2828 2542 2523 2642 2639 2549 2679 2872 2558 2757 2884 3000 2753 2937 2860 2704 2758 3585 3535 3750 3397 3458 3277 3756 3348 3320 3475 3528 3083 2985 3469 3327 3112 2933 3202 3213 3143 3066 3289 3231 3090 2657 3247 3191 2815 2818 3230 3258 2922 2822 2877 3274 3079 2899 3156 3119 2652 2683 2820 2794 2648 2389 2882 2765 2368 2451 2707 2939 2554 2727 2568 2982 2495 2399 2276 2392 2563 2588 2697 2816 2448 2392 2652 2564 2667 2532 2656 2612 2506 2612 2511 2816 2723 3115 3156 3363 3306 3315 3487 3910 3443 3280 3320 3488 3288 2917 3251 3373 2915 2855 3337 3389 3106 (ml/h/kg mouse) 3355 3236 3096 3278 3022 2969 2786 2728 2665 2785 2826 2930 2691 2793 2937 3809 3428 3358 3287 3085 3150 3112 3062 3074 2831 2940 2647 2633 2611 2689 2587 2665 2849 2815 3566 3460 3352 3223 3123 3169 2977 3057 3013 2957 2736 2601 2663 2693 2407 2637 2569 2576 2666 3235 3539 3344 3114 3172 SD 278 389 296 347 224 162 216 39 186 75 216 136 203 83 102 101 375 228 264 136 164 239 290 162 192 240 134 163 110 231 63 151 118 104 146 211 199 216 130 108 287 220 206 233 84 262 212 216 118 157 126 70 132 119 258 98 234 244 T im e (h r) 6.1 7.4 8.6 9.9 11.1 1 2 .4 13.6 14.9 16.1 1 7 .4 18.6 19.9 21.1 2 2 .4 2 3 .6 2 4 .9 26.1 2 7 .4 2 8 .6 2 9 .9 31.1 3 2 .4 3 3 .6 3 4 .9 36.1 3 7 .4 3 8 .6 3 9 .9 41.1 4 2 .4 4 3 .6 4 4 .9 46.1 4 7 .4 4 8 .6 4 9 .9 51.1 5 2 .4 5 3 .6 5 4 .9 56.1 5 7 .4 5 8 .6 5 9 .9 61.1 6 2 .4 6 3 .6 6 4 .9 66.1 6 7 .4 6 8 .6 6 9 .9 71.1 7 2 .4 7 3 .6 7 4 .9 76.1 7 7 .4 M e ta bolic ca g e s g ro u p 3: H F + 0 .0 3 % P F B S V O 2 (m l/h/kg m ouse) Average VO2 cage 0102 cage 0106 cage 0202 cage 0206 3472 3369 3160 3514 3395 3409 3368 3614 3050 3203 3449 3293 3172 2947 3117 3489 3251 3125 3816 3179 2926 3060 3395 2899 3037 2695 3096 3070 2788 2851 3097 2552 2871 2875 3325 2576 2799 2652 3518 2756 3056 3007 3074 2662 2601 2709 3117 2514 2805 2795 3413 2879 2750 2921 3103 2867 3171 2587 3536 2788 3833 3748 4154 3592 3636 3978 4043 3820 3312 3246 3549 3655 3416 2692 3359 3071 3230 3470 3388 3377 2869 2582 3516 3131 2856 2876 3552 3029 2994 2690 3323 2895 3079 2731 3477 3112 2968 3042 3324 2751 3173 2525 3366 2900 2704 2513 3166 2538 2718 2533 3179 2470 2628 2616 3017 2540 2607 2201 3282 3134 2730 2354 3253 2736 2797 2485 3350 2734 2698 2627 3198 2680 3046 2525 3342 2752 3577 3124 3851 3637 3845 3499 3852 3908 3451 3441 3668 3515 3181 2990 3312 3294 3346 2800 3445 3165 3086 2879 3554 3289 3090 3022 3415 3186 2863 2881 3403 3262 3087 3127 3591 3313 3056 2850 3467 3039 2671 3145 3078 2635 2444 2789 2892 2715 2399 2700 2935 2380 2342 2391 3212 2899 2545 2295 2815 2392 2404 2324 3006 2846 2463 2660 2803 2507 2455 2428 2845 2482 2691 2326 3266 2798 3248 2864 3489 3160 3502 3251 4078 3573 3217 3329 3610 3467 3102 2931 3421 3432 3005 2951 3571 3348 (ml/h/kg mouse) 3379 3446 3249 3181 3343 3070 2975 2822 2912 2931 2950 2735 2973 2910 3020 3832 3869 3441 3135 3366 3025 3078 2975 3100 3022 2991 2730 2725 2700 2806 2768 2842 2801 2916 3547 3776 3519 3194 3189 3202 3178 3102 3279 3103 2882 2710 2603 2711 2512 2645 2608 2553 2770 3190 3601 3406 3222 3219 SD 158 113 167 226 320 228 188 224 309 396 194 267 296 147 420 237 181 193 332 100 397 325 264 305 237 364 302 320 215 496 369 365 267 355 306 187 105 148 284 289 172 272 230 260 266 191 265 418 227 332 155 196 387 258 346 170 247 293 Page A41 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 T im e (hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 2 2 .4 2 3 .6 2 4 .9 26.1 2 7 .4 2 8 .6 2 9 .9 31.1 3 2 .4 3 3 .6 3 4 .9 36.1 3 7 .4 3 8 .6 3 9 .9 41.1 4 2 .4 4 3 .6 4 4 .9 46.1 4 7 .4 4 8 .6 4 9 .9 51.1 5 2 .4 5 3 .6 5 4 .9 56.1 5 7 .4 5 8 .6 5 9 .9 61.1 6 2 .4 6 3 .6 6 4 .9 66.1 6 7 .4 6 8 .6 6 9 .9 71.1 7 2 .4 7 3 .6 7 4 .9 76.1 7 7 .4 M eta bolic ca g e s gro u p 4: H F + 0 .006 % P F H S V O 2 (m l/h/kg m ouse) Average VO2 cage 0103 cage 0107 cage 0203 cage 0207 3575 3707 3794 3663 3438 3450 3743 3572 3276 3564 3720 3214 3298 3287 3705 3019 3219 3026 3779 3239 3263 3409 3672 3345 3253 2782 3223 2912 3148 2910 3420 2872 3131 3357 3169 2875 3100 3284 3191 2771 3016 2897 2977 2999 3076 3165 3223 2870 3085 2998 2948 2834 3053 2966 3152 3341 3230 3150 3288 3059 4037 4423 3777 3640 4262 4267 4205 4105 3794 3878 3828 3747 3514 3369 3957 3750 3148 3529 3640 3236 3395 3172 3650 3219 3149 2853 3984 3250 3169 3211 3921 3297 2970 2429 3604 3069 3160 2889 3350 3309 3016 3030 3543 3283 2941 2788 3214 2655 2850 2683 3085 2885 2941 2931 3210 2530 2907 2730 2981 2725 2942 2681 2965 2754 2796 2997 3440 2692 3066 3271 3046 3180 3205 2865 3259 2689 3687 3511 3496 3092 4214 3964 4094 3677 3775 3687 4344 3700 3674 3386 3911 3750 3475 3563 3848 3319 3342 2927 3707 3329 3292 3075 3560 3360 3037 2999 3737 3049 3252 3141 3706 3142 2949 2581 3450 2942 2998 2658 3240 2765 3028 2847 3009 2797 2891 2517 3312 2674 2898 2895 3049 2635 2599 2387 3169 3032 2763 2486 2988 2671 2667 2703 3097 2657 2847 2910 3004 2767 2862 2964 3025 2614 3237 3292 3296 2919 3789 4002 3796 3425 3950 3705 4281 3810 3367 2971 4117 3470 3409 3211 3938 3360 (ml/h/kg mouse) 3685 3551 3443 3327 3316 3422 3043 3088 3133 3086 2972 3084 2966 3128 3182 3969 4210 3812 3648 3388 3359 3309 3399 3018 3177 3218 2899 2876 2903 2836 2835 2981 3141 3005 3446 3987 3876 3680 3551 3326 3322 3206 3310 2980 2915 2920 2848 2869 2797 2727 2781 2882 2866 3186 3753 3937 3481 3480 SD 91 141 240 283 323 177 233 253 198 224 53 155 105 161 99 345 75 55 260 234 216 480 352 481 209 249 240 165 280 128 140 331 105 273 252 230 314 220 222 319 200 355 269 357 259 116 345 172 366 209 211 100 181 180 240 251 475 317 Tim e (hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 2 2 .4 2 3 .6 2 4 .9 26.1 2 7 .4 2 8 .6 2 9 .9 31.1 3 2 .4 3 3 .6 3 4 .9 36.1 3 7 .4 3 8 .6 3 9 .9 41.1 4 2 .4 4 3 .6 4 4 .9 46.1 4 7 .4 4 8 .6 4 9 .9 51.1 5 2 .4 5 3 .6 5 4 .9 56.1 5 7 .4 5 8 .6 5 9 .9 61.1 6 2 .4 6 3 .6 6 4 .9 66.1 6 7 .4 6 8 .6 6 9 .9 71.1 7 2 .4 7 3 .6 7 4 .9 76.1 7 7 .4 M eta bolic cag e s gro u p 6 : H F + 0.003 % P F O S V O 2 (m l/h/kg m ouse) Average VO2 cage 0104 cage 0108 cage 0204 cage 0208 3936 4321 3970 3628 3779 3980 3795 3648 3334 3807 3674 3379 3695 3783 3579 3441 3866 3646 3646 3141 3633 3225 3349 3124 3766 3107 3222 3167 3592 3471 3249 3007 3335 2903 3089 3039 3212 3171 2998 2777 3726 3504 3191 2894 3676 2963 2911 3007 3305 3099 2949 3046 3297 3319 2980 3014 3731 3204 3078 3199 4099 4024 3349 3392 4351 3972 4050 3767 3752 3870 4131 3917 3941 4064 3600 3773 3747 3497 3405 3448 3948 3675 3488 3364 3818 3178 3407 3492 3918 3425 3579 3323 3886 3428 3396 3234 3850 3073 3304 3074 3591 3040 3332 3159 3316 3011 2944 3124 3267 2725 2955 3142 3116 2830 2972 3019 3148 3212 2800 2929 3309 2822 3150 3182 3392 2842 2934 2916 3310 2932 3103 3085 3301 2919 2962 3075 3857 3307 3541 3244 4409 3774 3676 3620 3834 3995 3818 3874 4037 3881 3610 3592 3747 3731 3514 3608 3907 3451 3525 3338 3965 3167 3620 3404 3733 3412 3604 3462 3792 3344 3376 3424 3870 3327 3465 3392 3598 3153 3213 3205 3697 3167 3007 3175 3151 2771 3077 2885 3203 2934 2705 3044 2953 2527 2901 2845 3241 2925 2873 2718 3204 2665 2843 2776 3161 2950 2659 3014 3089 2860 2748 2780 3570 2917 2989 3115 3761 3686 3194 3269 3836 3329 3493 3677 3648 3583 3465 3833 3736 3613 3363 3688 (ml/h/kg mouse) 3963 3800 3549 3624 3575 3333 3315 3330 3091 3040 3329 3139 3100 3152 3303 3716 4035 3918 3845 3524 3619 3474 3561 3486 3325 3280 3099 3022 2984 3022 3116 3021 3108 3064 3487 3870 3880 3780 3650 3555 3539 3553 3484 3513 3292 3262 2971 2972 2806 2939 2872 2946 2869 3148 3477 3584 3632 3600 SD 283 136 229 148 307 220 304 258 180 198 364 360 150 180 291 400 242 158 202 153 254 265 260 280 366 239 163 236 119 191 208 250 155 171 278 365 80 217 110 247 339 145 208 245 205 301 174 209 192 220 233 211 154 293 287 220 154 166 Page A42 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Time ( hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 2 2 .4 2 3 .6 2 4 .9 26.1 2 7 .4 2 8 .6 2 9 .9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 4 2 .4 4 3 .6 4 4 .9 46.1 4 7 .4 4 8 .6 4 9 .9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 6 2 .4 6 3 .6 6 4 .9 66.1 6 7 .4 6 8 .6 6 9 .9 71.1 7 2 .4 7 3 .6 7 4 .9 76.1 7 7 .4 group 1 vs 3 nn p 4 4 0.886 4 4 0.343 4 4 0.486 4 4 0.886 4 4 0.343 4 4 0.686 4 4 0.486 4 4 0.343 4 4 0.200 4 4 0.886 4 4 0.686 4 4 0.343 4 4 0.200 4 4 0.200 4 4 0.886 4 4 1.000 4 4 0.114 4 4 0.686 4 4 0.686 4 4 0.057 4 4 0.686 4 4 0.886 4 4 0.686 4 4 0.886 4 4 0.343 4 4 0.886 4 4 1.000 4 4 0.886 4 4 0.886 4 4 0.886 4 4 0.343 4 4 0.686 4 4 0.343 4 4 0.886 4 4 0.886 4 4 0.057 4 4 0.486 4 4 0.886 4 4 0.686 4 4 0.886 4 4 0.686 4 4 0.686 4 4 0.114 4 4 0.886 4 4 0.886 4 4 0.486 4 4 0.486 4 4 0.886 4 4 0.686 4 4 1.000 4 4 0.886 4 4 0.343 4 4 0.886 4 4 1.000 4 4 0.686 4 4 0.686 4 4 0.334 4 4 0.886 gr n 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 VO2 , p-values Mann Whitney U-test 1 vs 4 group 1 vs 6 group 3 vs 4 group 3 vs 6 0.057 0.343 0.114 0.886 0.114 0.029 0.114 0.029 0.029 0.114 0.343 0.343 0.114 0.029 0.029 0.886 0.029 0.029 0.200 0.114 0.343 0.886 0.343 0.686 0.057 0.114 0.200 0.114 0.200 0.686 0.029 0.114 0.029 0.486 0.486 0.057 0.029 0.057 0.029 0.343 0.114 0.686 0.200 1.000 0.486 0.114 0.686 0.343 0.200 0.686 0.057 0.029 0.114 0.686 0.486 0.029 0.200 0.200 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 P 029 057 114 200 114 057 029 029 029 114 057 486 057 029 029 000 057 029 029 029 029 200 057 029 114 114 029 057 029 057 029 057 057 057 686 114 029 029 029 029 114 029 029 029 029 029 114 200 057 057 057 029 114 343 686 057 029 057 0 .0 2 9 0 .2 0 0 0 .3 4 3 0 .4 8 6 0 .8 8 6 0 .1 1 4 0 .6 8 6 0 .1 1 4 0 .2 0 0 0 .4 8 6 0 .4 8 6 0 .1 1 4 0 .4 8 6 0 .1 1 4 0 .6 8 6 0 .6 8 6 0 .0 2 9 0 .0 2 9 0 .0 5 7 0 .8 8 6 0 .2 0 0 0 .6 8 6 0 .2 0 0 0 .6 8 6 0 .4 8 6 0 .4 8 6 0 .3 4 3 0 .4 8 6 0 .6 8 6 1.000 0 .6 8 6 0 .6 8 6 0 .2 0 0 0 .8 8 6 0 .4 8 6 0 .2 0 0 0 .0 2 9 0 .0 2 9 0 .1 1 4 0 .4 8 6 0 .4 8 6 0 .6 8 6 0 .6 8 6 0 .4 8 6 0 .8 8 6 0 .1 4 0 0 .4 8 6 0 .8 8 6 0 .3 4 3 0 .8 8 6 0 .3 4 3 0 .0 5 7 0 .6 8 6 0 .8 8 6 0 .6 8 6 0 .0 2 9 0 .4 8 6 0 .3 4 3 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 p 0.029 0.029 0.114 0.057 0.486 0.200 0.029 0.057 0.200 0.486 0.200 0.200 0.343 0.114 0.343 0.686 0.486 0.029 0.029 0.114 0.114 0.200 0.029 0.200 0.200 0.486 0.200 0.200 0.114 0.686 0.200 0.200 0.200 0.686 0.886 0.886 0.029 0.029 0.029 0.200 0.200 0.029 0.200 0.200 0.029 0.029 0.114 0.486 0.114 0.343 0.114 0.057 0.686 0.886 0.886 0.200 0.029 0.057 group 4 vs 6 nn p 0.200 0.057 0.486 0.200 0.486 0.486 0.686 0.200 0.686 0.886 0.343 0.886 0.200 1.000 0.886 0.486 0.343 0.343 0.343 0.686 0.200 0.486 0.343 0.200 1.000 0.486 0.200 0.343 0.686 0.200 0.114 0.886 1.000 0.686 0.886 0.486 0.343 0.886 0.486 0.343 0.343 0.343 0.200 0.114 0.200 0.114 0.686 0.486 0.886 0.343 0.486 0.486 0.886 0.686 0.114 0.114 0.486 0.486 p< 0 .0 5 Page A43 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 CO2 production T im e (h r) 6.1 7 .4 8.6 9.9 11.1 1 2 .4 13.6 14.9 16.1 1 7 .4 18.6 19.9 21.1 2 2 .4 2 3 .6 2 4 .9 26.1 2 7 .4 2 8 .6 2 9 .9 31.1 3 2 .4 3 3 .6 3 4 .9 36.1 3 7 .4 3 8 .6 3 9 .9 41.1 4 2 .4 4 3 .6 4 4 .9 46.1 4 7 .4 4 8 .6 4 9 .9 51.1 5 2 .4 5 3 .6 5 4 .9 56.1 5 7 .4 5 8 .6 5 9 .9 61.1 6 2 .4 6 3 .6 6 4 .9 66.1 6 7 .4 6 8 .6 6 9 .9 71.1 7 2 .4 7 3 .6 7 4 .9 76.1 7 7 .4 M eta bolic ca g e s g ro u p 1 : H F control V C O 2 (m l/h/kg m ouse) cage 0101 cage 0105 cage 0201 cage 0205 2929 3110 3620 2845 2978 3408 3399 2787 2781 3142 3042 2814 2963 3025 3464 2655 2773 2718 2664 2841 2721 2759 3107 2565 2478 2629 2619 2308 2736 2708 2379 2391 2418 2501 2567 2267 2713 2207 2650 2315 3008 2361 2357 2233 2486 2419 2757 2474 2362 2412 2465 2231 2357 2731 2041 2440 2563 2617 2602 2402 3454 3237 3386 3369 2775 2971 3388 3044 3139 3105 3283 2578 2804 2718 3414 3120 2860 2861 2620 2568 3100 3243 2592 2750 2563 2568 3137 2730 2599 2436 2976 2197 2801 2505 2827 2280 2500 2421 2436 2334 2517 2267 2933 2241 2627 2470 2362 2518 2813 2873 2191 2345 2748 2440 2656 2095 2281 2470 2655 2354 2448 2244 2505 2168 2369 2400 2829 2209 2594 2662 2551 2631 2874 2543 2334 2510 3258 3226 3635 3092 3054 2903 3311 2877 3010 3083 3407 2777 2744 3012 3274 2839 2610 2778 2975 2727 2547 2403 2717 2640 3158 2997 2521 2341 2581 2784 3114 2383 2571 2393 2915 2423 2631 2574 2798 2088 2574 2152 2597 2128 2295 2478 2429 1822 2211 2536 2122 2019 2445 2461 1985 1914 2132 1693 1936 2008 2274 2161 2434 1765 1943 2025 2320 2073 1969 2239 2420 1970 2228 1950 2546 2267 2767 2844 2843 3169 3065 3474 2691 2866 2927 3054 3241 2818 2559 2840 3150 2531 2530 2822 2961 2683 Average VCO2 (ml/h/kg mouse) 3126 3143 2945 3027 2749 2788 2553 2509 2438 2471 2490 2534 2306 2453 2546 3361 3044 3026 3014 2793 2856 2750 2552 2603 2423 2490 2498 2552 2485 2440 2341 2451 2588 2587 3303 3036 3069 2967 2773 2736 2595 2715 2576 2523 2363 2256 2191 2232 1943 2159 2090 2150 2248 2841 3088 3010 2770 2749 SD 348 311 176 333 76 229 157 190 130 248 351 152 184 207 99 91 256 309 318 238 285 270 327 260 68 321 276 227 290 163 161 265 222 71 233 199 261 233 152 295 297 312 239 305 258 299 193 312 185 285 162 221 244 162 297 182 289 185 T im e (h r) 6.1 7.4 8.6 9.9 11.1 1 2 .4 13.6 14.9 16.1 1 7 .4 18.6 19.9 21.1 2 2 .4 2 3 .6 2 4 .9 26.1 2 7 .4 2 8 .6 2 9 .9 31.1 3 2 .4 3 3 .6 3 4 .9 36.1 3 7 .4 3 8 .6 3 9 .9 41.1 4 2 .4 4 3 .6 4 4 .9 46.1 4 7 .4 4 8 .6 4 9 .9 51.1 5 2 .4 5 3 .6 5 4 .9 56.1 5 7 .4 5 8 .6 5 9 .9 61.1 6 2 .4 6 3 .6 6 4 .9 66.1 6 7 .4 6 8 .6 6 9 .9 71.1 7 2 .4 7 3 .6 7 4 .9 76.1 7 7 .4 M eta bolic ca g e s g ro u p 3: H F + 0 .03 % P F B S V C O 2 (m l/h/kg m ouse) Average VCO2 cage 0102 cage 0106 cage 0202 cage 0206 3252 3003 2825 3076 3223 3131 3321 3262 2920 2824 3352 2920 2958 2601 2985 2986 3064 2849 3475 2676 2699 2726 3161 2520 2801 2151 2872 2743 2572 2481 2697 2060 2714 2400 3020 2190 2585 2148 3083 2324 2574 2524 2658 2156 2164 2181 2852 2015 2411 2426 3150 2209 2300 2522 2630 2256 2736 2188 3094 2372 3201 3308 3794 3129 3254 3232 3611 3130 2985 2775 3335 3196 3014 2175 3300 2743 2775 2675 3305 2895 2439 1920 3161 2671 2504 2269 3092 2606 2610 2010 2889 2378 2617 2140 2941 2590 2477 2465 2788 2208 2899 1937 2859 2524 2685 2169 3039 2355 2683 2199 3043 2262 2621 2408 2877 2293 2474 1986 2836 2555 2507 2197 2699 2100 2548 2105 2784 2263 2467 2244 2683 2211 2764 2233 3009 2456 3042 2866 3422 3123 3429 3157 3477 3172 3211 3074 3245 2974 3047 2715 2949 2936 3111 2508 3013 2564 2896 2513 3032 2765 2872 2595 2781 2578 2476 2380 2820 2651 2685 2602 2998 2616 2488 2275 2807 2394 2467 2477 2587 2067 2183 2398 2543 2186 1944 2326 2532 1776 1948 2041 2791 2344 2018 2013 2171 1721 1832 1903 2347 2267 1932 2169 2213 1916 1855 1854 2316 1905 2156 1965 2756 2343 2564 2510 2797 2630 3132 2821 3506 2895 2833 2869 3164 2960 2774 2421 3060 2920 2464 2451 2963 2853 (ml/h/kg mouse) 3039 3234 3004 2883 3016 2776 2642 2452 2581 2535 2478 2303 2549 2427 2598 3358 3307 3073 2808 2913 2548 2618 2472 2572 2485 2555 2562 2547 2550 2463 2376 2425 2401 2615 3113 3309 3126 2912 2799 2802 2707 2582 2725 2491 2399 2328 2145 2281 1981 2087 2057 1982 2305 2625 3088 2956 2794 2683 SD 177 80 236 188 345 272 331 276 363 407 222 374 413 179 402 300 210 245 480 277 515 346 372 329 237 445 383 394 257 354 276 301 219 341 232 168 125 140 307 221 144 194 186 228 228 176 346 380 188 257 155 224 338 125 308 149 275 264 Page A44 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 T im e (h r) 6.1 7 .4 8.6 9.9 11.1 1 2 .4 13.6 14.9 16.1 1 7 .4 18.6 19.9 21.1 2 2 .4 2 3 .6 2 4 .9 26.1 2 7 .4 2 8 .6 2 9 .9 31.1 3 2 .4 3 3 .6 3 4 .9 36.1 3 7 .4 3 8 .6 3 9 .9 41.1 4 2 .4 4 3 .6 4 4 .9 46.1 4 7 .4 4 8 .6 4 9 .9 51.1 5 2 .4 5 3 .6 5 4 .9 56.1 5 7 .4 5 8 .6 5 9 .9 61.1 6 2 .4 6 3 .6 6 4 .9 66.1 6 7 .4 6 8 .6 6 9 .9 71.1 7 2 .4 7 3 .6 7 4 .9 76.1 7 7 .4 M e ta bolic ca g e s g ro u p 4: H F + 0 .0 0 6 % P F H S V C O 2 (m l/h/kg m ouse) cage 0103 cage 0107 cage 0203 cage 0207 3309 3390 3535 3348 3243 2910 3195 3285 3526 3487 3375 2961 3013 2980 3360 2695 2848 2670 3385 2981 2803 3043 3222 3000 2757 2340 2802 2483 2834 2384 2957 2469 2699 2685 2527 2316 2641 2474 2677 2658 2628 2505 2448 2519 2501 3011 2615 2533 2834 2835 2489 2379 2638 2685 2634 2873 2739 2772 2653 2586 3504 3473 3331 3246 3532 3535 3688 3585 3236 3243 3539 3256 3498 3755 3374 3475 2940 3382 3493 3025 3109 2912 3516 3001 2575 2599 3708 2979 2536 2804 3465 2755 2419 1953 3136 2496 2531 2461 2999 2664 2613 2766 2818 2612 3063 2756 2466 2243 2533 2538 2510 2677 2656 2834 2715 2186 2367 2515 2371 2250 2316 2481 2372 2195 2273 2767 2861 2035 2587 2927 2695 2742 2771 3419 2605 3205 2987 3237 2323 2691 3884 3492 3775 3089 3549 3283 4014 3281 3537 3116 3646 3478 3286 3411 3615 3060 3013 2658 3123 3020 2856 2761 2950 3005 2482 2653 2458 2516 3004 2972 2631 2505 2446 2003 2852 2388 2471 2132 2679 2317 2444 2248 2508 2381 2317 1959 2651 2239 2384 2357 2281 2202 2092 1863 2403 2467 2089 2019 1983 2148 2360 2535 2074 2135 2254 2256 2476 2241 2189 2394 2578 2122 2792 2665 2648 2485 3502 3130 3196 2820 3708 2929 3755 3224 3218 2380 3623 3083 3192 2698 3327 2906 Average VCO2 (ml/h/kg mouse) 3395 3335 3161 3012 2971 3017 2596 2661 2557 2598 2539 2665 2634 2708 2687 3389 3585 3412 3432 3210 3135 2965 2890 2501 2664 2740 2594 2564 2598 2376 2341 2484 2738 2672 3138 3560 3532 3444 3343 2954 2893 2644 2662 2422 2400 2395 2292 2306 2206 2127 2209 2307 2321 2648 3162 3404 3076 3031 SD 99 148 274 273 304 172 221 278 179 102 81 236 236 113 84 121 73 137 240 269 267 528 401 487 239 259 245 76 284 109 119 395 142 280 312 355 345 230 233 204 108 252 217 348 232 111 285 82 281 163 225 113 207 126 280 397 518 283 T im e (h r) 6.1 7 .4 8.6 9.9 11.1 1 2 .4 1 3 .6 1 4 .9 16.1 1 7 .4 1 8 .6 1 9 .9 21.1 2 2 .4 2 3 .6 2 4 .9 26.1 2 7 .4 2 8 .6 2 9 .9 31.1 3 2 .4 3 3 .6 3 4 .9 36.1 3 7 .4 3 8 .6 3 9 .9 41.1 4 2 .4 4 3 .6 4 4 .9 46.1 4 7 .4 4 8 .6 4 9 .9 51.1 5 2 .4 5 3 .6 5 4 .9 56.1 5 7 .4 5 8 .6 5 9 .9 61.1 6 2 .4 6 3 .6 6 4 .9 66.1 6 7 .4 6 8 .6 6 9 .9 71.1 7 2 .4 7 3 .6 7 4 .9 76.1 7 7 .4 M e ta bolic ca g e s g ro u p 6 : H F + 0 .0 0 3 % P F O S V C O 2 (m l/h/kg m ouse) | Average VCO2 c a g e 0 1 0 4 c a g e 0 1 0 8 c a g e 0 2 0 4 c a g e 0 2 0 8 (ml/h/kg mouse) 3618 3732 3629 3220 3550 3414 3149 3553 3346 3365 3077 3062 3321 2963 3106 3331 3294 3219 3015 3215 3459 3188 3324 2801 3193 3301 2650 2970 2656 2894 3344 2303 2875 2554 2769 3167 2783 2760 2326 2759 2754 2270 2407 2550 2495 2745 2591 2365 2139 2460 3329 2992 2511 2371 2801 3154 2288 2097 2433 2493 2765 2771 2441 2405 2595 2658 2817 2364 2466 2576 3248 2519 2387 2668 2705 3643 3328 2734 2974 3170 3711 3457 3256 3206 3408 3410 3409 3637 3476 3483 3586 3714 3225 3340 3466 3324 3143 3102 2929 3124 3436 3095 3183 2900 3153 3213 2431 3022 2895 2890 3040 2809 3004 2693 2887 3259 2784 2951 2688 2921 3172 2333 2737 2351 2648 3179 2503 2817 2633 2783 3080 2433 2362 2717 2648 2992 2068 2449 2838 2587 2701 2306 2399 2627 2508 2828 2532 2224 2310 2474 2695 2234 2681 2499 2527 2775 2233 2426 2409 2461 2741 2411 2500 2573 2556 2766 2411 2616 2534 2582 3454 2739 3044 2867 3026 3931 3266 3167 3104 3367 3393 3634 3407 3247 3420 3656 3495 3236 3014 3350 3109 3309 3021 3121 3140 3360 2940 2868 2811 2995 3313 2510 2896 2675 2849 3183 2708 2683 2661 2809 3210 2732 2631 2576 2787 3309 2775 2552 2529 2791 3020 2472 2453 2522 2617 2882 2549 2424 2522 2594 2636 2062 2504 2233 2359 2675 2302 2208 2333 2379 2419 2040 2197 2131 2197 2724 2379 2060 2004 2291 2533 2023 2195 1971 2180 2450 2344 2016 2234 2261 2505 2242 1969 2016 2183 3034 2294 2265 2426 2505 3260 3089 2531 2702 2895 3398 2900 2924 3037 3065 3198 3204 3044 3244 3172 3051 3148 2734 3064 2999 SD 226 168 152 141 284 310 449 344 207 265 441 462 200 201 380 399 230 107 224 162 223 333 165 251 396 294 326 414 186 270 215 227 140 149 312 382 160 283 121 249 348 250 289 363 270 199 260 204 161 332 254 185 246 360 337 230 88 182 Page A45 of A172 Appendix to TNO-report of 3M-02_____________ Final version Time ( hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 group 1 vs 3 nn p 4 4 0.886 4 4 1.000 4 4 0.686 4 4 0.486 4 4 0.200 4 4 0.886 4 4 0.343 4 4 0.886 4 4 0.886 4 4 1.000 4 4 0.886 4 4 0.343 4 4 0.486 4 4 1.000 4 4 1.000 4 4 0.486 4 4 0.200 4 4 0.886 4 4 0.686 4 4 0.486 4 4 0.343 4 4 0.486 4 4 0.886 4 4 1.000 4 4 0.686 4 4 0.886 4 4 1.000 4 4 0.886 4 4 1.000 4 4 0.686 4 4 0.886 4 4 0.886 4 4 0.343 4 4 1.000 4 4 0.343 4 4 0.114 4 4 0.886 4 4 0.886 4 4 1.000 4 4 0.886 4 4 0.686 4 4 0.686 4 4 0.200 4 4 0.886 4 4 0.886 4 4 1.000 4 4 0.886 4 4 0.886 4 4 0.486 4 4 0.886 4 4 0.686 4 4 0.200 4 4 0.886 4 4 0.114 4 4 1.000 4 4 0.886 4 4 1.000 4 4 0.886 gr n 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 (/) > p 0.343 0.686 0.343 1.000 0.200 0.200 0.686 0.486 0.343 0.889 0.343 0.200 0.057 0.200 0.114 0.686 0.029 0.057 0.114 0.114 0.200 0.489 0.343 0.686 0.057 0.343 0.886 0.486 0.486 0.886 1.000 1.000 0.343 0.686 0.686 0.057 0.114 0.057 0.029 0.486 0.200 0.886 0.486 0.686 0.886 0.686 0.686 1.000 0.343 0.686 0.486 0.200 0.886 0.114 0.886 0.200 0.486 0.200 VCO2, p-values Mann Whitney U-test group 1 vs 6 nn E 4 0.114 group 3 vs 4 group 3 vs 6 3A Y4nnI n p n0 .(0 2. 9 4 0.057 4 0.343 4 0.486 4 0.200 4 0.343 4 0.486 4 0.343 4 0.486 4 0.486 4 0.029 4 0.057 4 0.686 4 0.686 4 0.886 4 0.200 4 0.886 4 0.686 4 0.886 4 0.686 4 0.200 4 0.686 4 0.200 4 0.886 4 0.886 4 1.000 4 1.000 4 0.486 4 1.000 4 0.200 4 0.686 4 0.686 4 0.486 4 0.200 4 0.486 4 0.114 4 0.686 4 0.686 4 0.486 4 0.029 4 0.343 4 0.886 4 0.686 4 0.686 4 0.486 4 0.486 4 0.686 4 0.114 4 0.200 4 0.486 4 0.029 4 0.057 4 0.029 4 0.114 4 0.114 4 0.057 4 0.057 4 0.114 4 0.200 4 0.200 4 0.200 4 0.114 4 0.686 4 0.486 4 0.486 4 0.114 4 0.343 4 0.114 4 0.343 4 0.686 4 0.114 4 0.886 4 0.486 4 0.886 4 0.343 4 0.886 4 0.886 4 0.486 4 0.886 4 0.486 4 1.000 4 1.000 4 1.000 4 0.886 4 0.886 4 1.000 4 1.000 4 0.486 4 0.886 4 0.343 4 0.886 4 0.686 4 0.686 4 0.886 4 1.000 4 0.886 4 0.057 4 0.343 4 0.886 4 0.886 4 1.000 4 0.200 4 0.886 4 0.886 4 0.200 4 0.343 4 0.886 4 0.114 4 0.029 4 0.029 4 0.114 4 0.029 4 0.057 4 0.029 4 0.057 4 0.114 4 0.200 4 0.486 4 0.486 4 0.343 4 0.200 4 0.686 4 0.686 4 0.886 4 0.200 4 0.200 4 0.486 4 0.886 4 0.886 4 0.886 4 0.200 4 0.686 4 1.000 4 0.686 4 0.114 4 0.686 4 0.114 4 0.343 4 0.686 4 0.486 4 0.686 4 0.686 4 0.886 4 0.114 4 0.343 4 0.114 4 0.886 4 0.686 4 0.343 4 0.886 4 0.686 4 0.486 4 0.486 4 0.200 4 0.114 4 0.886 4 0.886 4 0.886 4 0.200 4 0.886 4 0.343 4 0.486 4 1.000 4 0.486 4 1.000 4 0.114 4 0.486 4 0.057 4 0.343 4 0.057 4 0.114 4 0.200 4 0.114 group 4 vs 6 0.343 0.886 0.886 0.343 0.486 0.486 0.686 1.000 0.886 0.486 0.686 0.343 0.686 0.486 0.686 0.486 0.343 0.686 1.000 0.686 1.000 1.000 0.686 0.200 0.886 0.886 1.000 1.000 0.486 0.886 0.200 1.000 0.114 0.686 0.886 0.886 0.886 0.886 0.343 0.886 0.686 0.200 0.486 0.200 0.343 0.114 1.000 0.886 1.000 0.686 0.886 0.686 0.486 0.343 0.343 0.200 1.000 1.000 04-12-2006 p< 0.05 Page A46 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Respiratory exchange ratio Time Jhr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 Metabolic cages group 1: HF control Respiratory exchange ratio Average cage 0101 cage 0105 cage 0201 cage 0205 RER 0.960 0.861 1.015 0.895 0.933 1.025 0.902 1.037 0.934 0.974 0.997 0.900 0.994 0.931 0.955 0.971 0.854 0.962 0.909 0.924 1.014 0.848 0.906 0.884 0.913 0.966 0.933 0.975 0.885 0.940 0.939 0.841 1.000 0.892 0.918 0.981 0.839 0.976 0.883 0.920 1.008 0.890 0.926 0.845 0.917 0.962 0.817 0.917 0.837 0.883 0.969 0.824 0.905 0.815 0.878 0.896 0.827 0.936 0.792 0.863 0.906 0.821 0.895 0.803 0.856 0.877 0.824 0.966 0.843 0.878 0.852 0.876 0.867 0.862 0.864 0.908 0.878 0.890 0.857 0.883 0.941 0.886 0.960 0.785 0.893 0.923 0.877 0.936 0.853 0.897 0.965 0.823 1.007 0.877 0.918 0.963 0.802 0.995 0.866 0.906 0.961 0.784 0.977 0.903 0.906 0.926 0.805 0.952 0.856 0.885 0.948 0.765 0.876 0.747 0.834 0.889 0.809 0.881 0.797 0.844 0.879 0.780 0.907 0.870 0.859 0.882 0.764 0.894 0.821 0.840 0.985 0.920 0.998 0.865 0.942 1.030 0.936 1.040 0.881 0.972 1.027 0.916 1.012 0.856 0.953 0.972 0.882 0.947 0.827 0.907 0.962 0.890 0.946 0.814 0.903 0.930 0.892 0.985 0.863 0.917 0.940 0.882 0.959 0.845 0.906 0.905 0.920 0.941 0.908 0.918 0.913 0.916 0.968 0.915 0.928 0.881 0.886 0.881 0.856 0.876 0.907 0.888 0.964 0.901 0.915 0.919 0.870 0.981 0.910 0.920 0.892 0.870 0.923 0.871 0.889 0.832 0.827 0.975 0.812 0.861 0.907 0.816 0.943 0.828 0.874 0.916 0.865 0.956 0.813 0.887 0.910 0.831 0.888 0.781 0.853 0.903 0.817 0.899 0.787 0.851 0.964 0.763 0.931 0.802 0.865 0.963 0.861 0.875 0.766 0.867 0.896 0.774 0.830 0.772 0.818 0.933 0.784 0.817 0.759 0.823 0.890 0.745 0.810 0.783 0.807 0.876 0.794 0.857 0.721 0.812 0.811 0.758 0.907 0.772 0.812 0.777 0.839 0.926 0.785 0.832 0.852 0.775 0.903 0.830 0.840 0.887 0.901 0.912 0.814 0.878 0.855 0.909 0.890 0.831 0.871 0.891 0.921 0.931 0.854 0.899 0.870 0.873 0.930 0.866 0.885 0.888 0.844 0.872 0.864 0.867 SD 0.069 0.067 0.048 0.054 0.072 0.041 0.068 0.070 0.069 0.068 0.073 0.065 0.052 0.063 0.010 0.022 0.079 0.039 0.083 0.089 0.087 0.067 0.095 0.047 0.055 0.060 0.062 0.076 0.081 0.066 0.067 0.053 0.052 0.016 0.027 0.013 0.033 0.046 0.025 0.076 0.062 0.062 0.058 0.059 0.097 0.080 0.059 0.077 0.062 0.070 0.067 0.069 0.053 0.044 0.035 0.035 0.030 0.018 Time (hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 Metabolic cages group 3: HF + 0.03 % PFBS Respiratory exchange ratio Average cage 0102 cage 0106 cage 0202 cage 0206 RER 0.937 0.894 0.893 0.878 0.900 0.950 0.919 0.987 0.903 0.940 0.959 0.882 0.972 0.887 0.925 0.931 0.884 0.959 0.856 0.908 0.944 0.910 0.909 0.842 0.901 0.922 0.889 0.932 0.869 0.903 0.920 0.800 0.928 0.895 0.886 0.923 0.867 0.867 0.805 0.866 0.946 0.831 0.908 0.851 0.884 0.927 0.808 0.874 0.841 0.862 0.836 0.832 0.863 0.807 0.834 0.831 0.804 0.916 0.803 0.839 0.855 0.863 0.921 0.763 0.851 0.833 0.858 0.847 0.780 0.830 0.858 0.846 0.874 0.849 0.857 0.834 0.878 0.913 0.871 0.874 0.894 0.812 0.895 0.818 0.855 0.901 0.856 0.943 0.875 0.894 0.887 0.809 0.982 0.893 0.892 0.858 0.771 0.975 0.855 0.865 0.851 0.743 0.896 0.855 0.837 0.877 0.783 0.862 0.859 0.845 0.871 0.744 0.867 0.823 0.826 0.850 0.779 0.842 0.830 0.825 0.837 0.802 0.835 0.801 0.819 0.922 0.765 0.852 0.871 0.852 0.994 0.868 0.960 0.929 0.938 0.988 0.870 0.957 0.917 0.933 0.998 0.920 0.955 0.904 0.944 0.949 0.901 0.864 0.811 0.881 0.916 0.931 0.829 0.766 0.860 0.912 0.842 0.825 0.824 0.851 0.912 0.851 0.833 0.821 0.854 0.906 0.883 0.900 0.893 0.895 0.854 0.919 0.888 0.861 0.881 0.890 0.902 0.902 0.809 0.876 0.929 0.892 0.882 0.845 0.887 0.958 0.907 0.892 0.893 0.912 0.928 0.895 0.873 0.808 0.876 0.938 0.875 0.853 0.840 0.877 0.930 0.855 0.814 0.809 0.852 0.864 0.826 0.829 0.812 0.833 0.870 0.829 0.832 0.790 0.830 0.815 0.800 0.811 0.783 0.802 0.922 0.786 0.840 0.784 0.833 0.884 0.858 0.880 0.803 0.856 0.809 0.860 0.861 0.746 0.819 0.833 0.854 0.863 0.801 0.838 0.793 0.877 0.770 0.719 0.790 0.759 0.822 0.778 0.790 0.787 0.783 0.814 0.789 0.760 0.787 0.754 0.758 0.811 0.767 0.772 0.794 0.844 0.841 0.835 0.828 0.787 0.873 0.794 0.830 0.821 0.894 0.867 0.862 0.809 0.858 0.879 0.856 0.875 0.854 0.866 0.892 0.826 0.893 0.850 0.866 0.821 0.826 0.826 0.853 0.831 SD 0.025 0.037 0.047 0.046 0.042 0.029 0.059 0.048 0.053 0.051 0.023 0.053 0.065 0.034 0.013 0.032 0.046 0.037 0.071 0.084 0.065 0.042 0.059 0.032 0.020 0.065 0.053 0.051 0.042 0.059 0.077 0.041 0.040 0.010 0.030 0.045 0.034 0.031 0.051 0.044 0.056 0.022 0.033 0.014 0.065 0.037 0.054 0.027 0.066 0.027 0.022 0.026 0.023 0.039 0.036 0.013 0.033 0.014 Page A47 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 T im e (h r) 6.1 7 .4 8 .6 9 .9 11.1 1 2 .4 1 3 .6 1 4 .9 16.1 1 7 .4 1 8 .6 1 9 .9 21.1 2 2 .4 2 3 .6 2 4 .9 26.1 2 7 .4 2 8 .6 2 9 .9 31.1 3 2 .4 3 3 .6 3 4 .9 36.1 3 7 .4 3 8 .6 3 9 .9 41.1 4 2 .4 4 3 .6 4 4 .9 46.1 4 7 .4 4 8 .6 4 9 .9 51.1 5 2 .4 5 3 .6 5 4 .9 56.1 5 7 .4 5 8 .6 5 9 .9 61.1 6 2 .4 6 3 .6 6 4 .9 66.1 6 7 .4 6 8 .6 6 9 .9 71.1 7 2 .4 7 3 .6 7 4 .9 76.1 7 7 .4 M e ta b o lic c a g e s g ro u p 4: H F + 0 .0 0 6 % P F H S R e s p ira to ry e x c h a n g e ratio Average cage 0103 cage 0107 cage 0203 cage 0207 RER 0 .9 2 7 0 .9 1 8 0 .9 3 2 0 .9 1 3 0.922 0 .9 4 4 0 .9 2 5 0 .9 4 2 0 .9 4 4 0.939 0 .8 8 9 0 .9 2 0 0 .9 3 8 0 .9 2 2 0.917 0 .9 1 3 0 .9 0 5 0 .9 0 7 0 .8 9 4 0.905 0 .8 8 5 0.881 0 .8 9 6 0 .9 2 0 0.895 0 .8 5 8 0 .8 8 9 0 .8 7 6 0 .8 9 5 0.880 0 .8 4 8 0 .8 4 3 0 .8 6 9 0 .8 5 2 0.853 0.901 0 .8 1 7 0.861 0 .8 6 0 0.860 0 .8 6 2 0.791 0 .7 9 5 0 .8 0 2 0.812 0.851 0 .8 0 7 0 .8 2 3 0 .8 8 4 0.841 0 .8 2 0 0 .9 1 8 0 .8 4 3 0 .8 3 7 0.854 0 .8 1 0 0 .9 5 2 0 .8 0 3 0 .8 8 4 0.862 0 .9 1 9 0 .9 4 3 0 .8 4 2 0 .8 3 9 0.886 0 .8 6 3 0 .9 0 5 0 .8 2 4 0 .8 5 7 0.862 0 .8 4 5 0 .8 8 0 0 .8 0 2 0 .8 4 5 0.843 0 .8 6 8 0 .7 8 7 0 .8 7 9 0 .8 8 8 0.855 0 .8 2 9 0 .8 2 8 0 .8 7 5 0.871 0.851 0 .8 5 5 0 .9 1 2 0 .9 1 2 0 .8 9 9 0.894 0 .9 2 2 0 .9 6 8 0 .9 4 8 0 .9 2 6 0.941 0 .9 3 3 0 .9 5 9 0 .9 6 0 0 .9 3 4 0.947 0 .9 1 5 0 .9 1 9 0 .9 6 3 0 .9 3 2 0.932 0 .8 1 5 0 .9 1 2 0 .9 3 0 0 .9 1 6 0.893 0 .7 9 5 0 .8 7 2 0 .8 8 2 0 .8 3 3 0.846 0 .8 1 3 0 .8 0 6 0 .8 7 0 0 .8 1 2 0.825 0 .7 9 4 0.851 0 .8 9 6 0.801 0.836 0 .8 6 6 0 .9 3 8 0 .8 6 6 0 .7 4 9 0.855 0 .9 4 2 0 .9 3 9 0 .8 5 6 0 .8 4 5 0.895 0 .8 9 0 0 .9 4 5 0 .8 1 2 0 .9 2 9 0.894 0 .9 0 3 0 .9 6 8 0 .8 4 3 0 .8 6 7 0.895 0 .8 1 2 0 .9 1 9 0 .7 9 5 0.821 0.837 0.781 0 .9 2 5 0 .7 9 6 0 .7 9 4 0.824 0 .8 1 3 0 .9 2 3 0 .8 2 9 0 .7 5 4 0.830 0 .8 4 0 0 .8 9 2 0 .8 8 4 0 .8 5 7 0.868 0 .8 6 0 0 .9 1 0 0 .9 1 5 0.861 0.887 0 .9 2 5 0 .9 1 3 0 .9 2 4 0.871 0.908 0 .9 2 2 0 .8 8 2 0.921 0 .8 3 9 0.891 0 .9 3 9 0 .8 9 0 0 .9 2 2 0 .8 8 5 0.909 0 .9 6 4 0 .9 1 9 0.931 0 .9 2 6 0.935 0 .9 4 5 0 .9 5 8 0 .9 4 0 0 .9 2 2 0.941 0 .9 0 0 0 .9 0 9 0 .8 4 0 0 .9 0 8 0.889 0 .8 6 3 0 .8 9 8 0 .8 3 0 0 .8 9 3 0.871 0 .8 1 9 0 .8 1 9 0 .8 0 3 0 .8 6 2 0.826 0 .8 1 4 0.801 0 .8 0 3 0 .7 9 2 0.803 0 .8 2 3 0 .7 7 7 0 .8 2 9 0 .8 1 0 0.810 0 .8 2 0 0 .8 0 3 0 .8 2 8 0 .8 3 9 0.822 0 .8 0 9 0 .7 8 6 0 .8 3 4 0 .8 4 9 0.819 0.801 0 .7 7 7 0 .7 9 5 0 .8 3 8 0.803 0 .8 1 7 0.811 0 .7 4 5 0 .8 3 2 0.801 0 .8 0 2 0.781 0 .7 5 3 0 .8 0 6 0.786 0 .7 5 4 0 .7 9 8 0 .7 8 5 0.771 0.777 0 .7 5 4 0 .7 8 6 0 .8 2 0 0 .7 9 6 0.789 0 .7 8 9 0 .7 6 9 0 .8 1 9 0 .8 0 3 0.795 0 .7 6 3 0 .8 0 2 0 .8 4 6 0 .8 0 9 0.805 0 .8 6 2 0 .8 0 9 0 .8 0 4 0 .8 5 0 0.831 0 .9 2 4 0.781 0.841 0 .8 2 2 0.842 0 .9 3 9 0 .7 8 9 0 .8 7 7 0 .8 4 6 0.863 0 .9 5 5 0 .7 9 9 0 .8 7 8 0 .8 8 8 0.880 0 .9 3 6 0 .8 3 6 0.841 0 .8 6 0 0.868 SD 0.008 0.009 0.020 0.008 0.018 0.016 0.012 0.034 0.034 0.034 0.044 0.070 0.053 0.033 0.032 0.046 0.026 0.027 0.021 0.015 0.022 0.053 0.040 0.030 0.048 0.078 0.052 0.059 0.055 0.056 0.068 0.070 0.024 0.030 0.025 0.040 0.026 0.020 0.015 0.033 0.031 0.025 0.009 0.023 0.015 0.028 0.026 0.039 0.025 0.019 0.027 0.021 0.034 0.029 0.060 0.063 0.064 0.047 T im e (h r) 6.1 7 .4 8.6 9.9 11.1 1 2 .4 1 3 .6 1 4 .9 16.1 1 7 .4 1 8 .6 1 9 .9 21.1 2 2 .4 2 3 .6 2 4 .9 26.1 2 7 .4 2 8 .6 2 9 .9 31.1 3 2 .4 3 3 .6 3 4 .9 36.1 3 7 .4 3 8 .6 3 9 .9 41.1 4 2 .4 4 3 .6 4 4 .9 46.1 4 7 .4 4 8 .6 4 9 .9 51.1 5 2 .4 5 3 .6 5 4 .9 56.1 5 7 .4 5 8 .6 5 9 .9 61.1 6 2 .4 6 3 .6 6 4 .9 66.1 6 7 .4 6 8 .6 6 9 .9 71.1 7 2 .4 7 3 .6 7 4 .9 76.1 7 7 .4 M e ta b o lic c a g e s g ro u p 6 : H F + 0 .0 0 3 % P F O S R e s p ira to ry e x c h a n g e ratio | Average cage 0104 cage 0108 cage 0204 cage 0208 RER 0 .9 2 0 0 .8 6 3 0 .9 1 4 0 .8 8 8 0.896 0 .9 0 3 0 .7 9 0 0 .9 3 5 0 .9 1 6 0.886 0 .9 2 3 0 .8 0 2 0 .9 0 3 0 .8 7 8 0.876 0 .9 0 0 0.871 0 .8 9 9 0 .8 7 7 0.887 0 .8 9 4 0 .8 7 4 0.911 0.891 0.892 0 .9 0 9 0.821 0 .8 8 7 0 .8 5 0 0.867 0 .8 8 8 0.741 0 .8 9 3 0 .7 9 9 0.830 0 .8 8 2 0 .7 9 6 0 .8 4 8 0 .7 7 4 0.825 0 .8 2 6 0 .7 8 2 0 .7 7 7 0 .8 3 9 0.806 0 .8 5 5 0 .8 1 7 0 .7 8 7 0.771 0.808 0.891 0 .8 5 0 0 .7 8 2 0 .8 1 4 0.834 0 .8 5 3 0 .7 7 2 0 .7 1 8 0 .8 0 5 0.787 0 .8 3 5 0 .8 9 5 0 .8 2 8 0 .7 8 5 0.836 0 .8 0 6 0 .8 4 5 0 .7 9 3 0 .8 1 8 0.815 0 .8 6 8 0 .7 8 4 0.771 0 .8 3 0 0.813 0 .8 9 2 0 .8 2 8 0 .8 1 4 0 .8 7 5 0.852 0.851 0.871 0 .8 0 4 0 .8 4 8 0.844 0 .9 0 8 0.881 0 .8 7 9 0 .8 8 6 0.888 0.911 0 .9 1 4 0 .8 9 4 0 .8 8 5 0.901 0 .8 8 6 0 .9 0 0 0 .9 0 9 0 .8 4 8 0.885 0 .8 6 8 0 .8 4 0 0 .9 1 2 0 .8 6 2 0.871 0 .8 4 3 0 .7 6 4 0 .8 8 8 0 .8 2 7 0.830 0 .7 7 6 0 .8 1 9 0 .8 3 6 0 .8 1 2 0.811 0 .8 3 6 0 .8 1 2 0 .8 6 5 0 .8 3 0 0.836 0 .8 2 4 0 .7 5 6 0 .8 2 8 0.761 0.792 0 .8 9 0 0 .8 2 5 0 .8 4 7 0 .8 3 9 0.850 0 .9 2 9 0 .8 0 7 0.801 0 .8 6 9 0.852 0 .9 1 6 0 .7 5 9 0 .8 2 8 0 .9 0 2 0.851 0 .8 6 7 0 .8 1 3 0 .8 0 7 0.871 0.839 0 .8 9 8 0 .7 8 4 0 .7 9 3 0 .7 9 0 0.816 0 .8 0 8 0 .7 8 7 0 .8 4 6 0 .7 8 2 0.806 0 .8 1 6 0 .7 8 5 0 .8 3 0 0 .8 2 5 0.814 0 .8 2 7 0 .8 2 0 0 .8 0 4 0 .8 3 4 0.821 0 .8 3 6 0 .8 2 6 0 .8 8 5 0 .8 2 2 0.842 0 .8 9 6 0 .8 2 7 0 .8 5 9 0 .8 8 3 0.866 0 .8 9 0 0 .8 6 4 0 .8 6 0 0 .8 5 7 0.868 0 .8 8 5 0 .9 0 9 0.891 0 .8 3 6 0.880 0 .9 0 5 0.901 0 .8 9 7 0 .8 3 7 0.885 0 .8 2 9 0 .8 8 5 0 .8 6 0 0.861 0.859 0 .8 6 0 0 .8 5 2 0 .8 1 3 0.841 0.841 0 .8 3 5 0 .7 9 2 0 .7 9 9 0 .7 8 4 0.802 0 .8 5 2 0 .7 9 5 0 .7 4 3 0 .7 6 8 0.790 0 .8 4 6 0 .8 1 7 0 .7 7 9 0 .7 5 0 0.798 0 .8 5 5 0 .8 3 4 0 .7 3 5 0 .7 4 5 0.792 0.841 0 .7 8 3 0 .7 6 2 0 .7 8 4 0.793 0 .7 8 2 0 .8 0 3 0 .8 0 6 0 .7 9 5 0.797 0 .8 3 8 0.741 0 .8 1 3 0 .7 7 2 0.791 0 .8 3 3 0 .7 7 6 0 .8 1 6 0 .7 6 3 0.797 0 .8 2 0 0 .8 0 7 0 .7 5 3 0 .7 4 9 0.782 0 .8 3 3 0.811 0 .7 1 5 0 .7 3 6 0.774 0 .7 8 7 0 .7 5 8 0 .7 6 6 0 .7 0 9 0.755 0 .7 7 3 0 .7 9 2 0 .7 5 7 0 .7 3 3 0.764 0 .8 0 9 0 .7 8 2 0 .7 1 5 0 .7 2 2 0.757 0 .8 5 0 0 .7 8 6 0 .7 5 5 0 .7 7 5 0.792 0 .8 6 8 0 .8 3 8 0 .7 8 8 0 .8 2 5 0.830 0 .8 8 5 0.871 0 .8 3 5 0 .8 2 5 0.854 0 .8 7 6 0 .8 9 3 0 .8 7 8 0 .8 4 6 0.873 0 .8 1 4 0 .8 6 9 0.811 0 .8 3 2 0.832 SD 0.026 0.066 0.053 0.015 0.015 0.039 0.074 0.049 0.031 0.037 0.047 0.057 0.045 0.022 0.044 0.037 0.028 0.013 0.014 0.027 0.030 0.051 0.025 0.022 0.039 0.028 0.060 0.073 0.034 0.055 0.029 0.020 0.013 0.029 0.030 0.015 0.031 0.032 0.023 0.021 0.023 0.047 0.042 0.061 0.034 0.011 0.043 0.033 0.037 0.057 0.033 0.025 0.046 0.041 0.033 0.028 0.020 0.027 Page A48 of A172 Appendix to TNO-report of 3M-02_____________ Final version 04-12-2006 Time ( hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 group 1 vs 3 nn p 4 4 0.486 4 4 0.686 4 4 0.343 4 4 0.686 4 4 0.886 4 4 0.200 4 4 0.686 4 4 0.343 4 4 0.686 4 4 0.886 4 4 0.686 4 4 0.886 4 4 1.000 4 4 0.486 4 4 0.343 4 4 0.886 4 4 0.686 4 4 1.000 4 4 0.886 4 4 0.486 4 4 0.200 4 4 0.686 4 4 0.686 4 4 0.686 4 4 0.343 4 4 0.886 4 4 1.000 4 4 0.486 4 4 0.886 4 4 0.686 4 4 0.486 4 4 0.114 4 4 0.200 4 4 0.057 4 4 0.200 4 4 0.343 4 4 0.343 4 4 0.686 4 4 0.886 4 4 0.343 4 4 0.486 4 4 0.200 4 4 0.686 4 4 0.200 4 4 0.686 4 4 1.000 4 4 1.000 4 4 0.486 4 4 0.686 4 4 0.486 4 4 1.000 4 4 0.114 4 4 0.886 4 4 0.114 4 4 0.886 4 4 0.343 4 4 0.686 4 4 0.057 Respiratory exchange ratio, p-values Mann Whitney U-test group 1 vs 4 group 1 vs 6 group 3 vs 4 group 3 vs 6 group 4 vs 6 nn p nn n 4 4 [ 1.0001 4 | 4 0.686 0.343 4 p 0.886 0.200 4 I 0.886 I 4 4 0.343 1.000 4 0.343 0.057 4 [ 0.344 4 | 4 0.114 1.000 4 0.343 0.343 4 I 0.486 I 4 4 0.343 1.000 4 0.686 0.114 4 I 1.000 | 4 4 1.000 0.686 4 0.686 0.886 4 10.114 4 | 4 0.114 0.486 4 0.200 0.686 4 | 0.343 | 4 4 0.200 0.343 4 0.114 1.000 4 [ 0.344 4 | 4 0.114 0.686 4 0.343 0.343 4 | 0 .057| 4 | 4 0.029 0.114 4 0.057 0.686 4 \ 0.486 | 4 4 0.200 4 I 1.000 I 4 4 0.343 0.686 4 0.486 4 0.200 1.000 0.343 0.686 4 I 1.000 | 4 4 0.200 0.886 4 0.486 0.200 40 4 0.886 0.886 4 0.686 0.114 4 | 0 .886| 4| | 4 0.114 0.343 4 0.486 0.057 4 \ 0.343 | 4 4 0.200 0.343 4 0.200 0.343 4 [ 0.484 4 | 4 0.343 0.886 4 0.486 1.000 4 | 0.343 | 4 4 0.343 1.000 4 0.686 0.686 4 | 0.886 | 4 4 1.000 1.000 4 0.886 0.486 4 | 0 .886| 4 | 4 1.000 0.343 4 0.686 0.029 4 \ 1.000 | 4 4 0.886 0.343 4 0.686 0.029 4 | 0 .886| 4 | 4 0.486 0.029 4 0.486 0.029 4 [ 1.004 4 | 4 0.343 0.200 4 0.686 0.200 4 \ 0.886 | 4 4 1.000 0.486 4 0.486 0.343 4 | 0 .886| 4 | 4 1.000 0.886 4 1.000 0.486 4 \ 0.686 | 4 4 0.114 0.886 4 0.343 0.343 4 \ 1.000 | 4 4 0.886 1.000 4 0.686 0.686 4 | 0 .343| 4 | 4 0.200 0.343 4 0.200 0.343 4 \ 0.343 4 4 0.114 0.486 4 0.114 0.486 4 [ 0.344 4 | 4 0.114 0.200 4 0.029 0.343 4 \ 0.114 I 4 4 0.114 0.486 4 0.114 0.200 4 \ 0.114 | 4 4 0.057 0.686 4 0.486 1.000 4 [ 0.114 4 | 4 0.029 0.686 4 0.343 1.000 4 | 0.486 | 4 4 0.029 0.486 4 0.200 0.029 4 [ 0.344 4 | 4 0.029 1.000 4 0.057 0.114 4 | 0.686 | 4 4 0.029 0.200 4 0.686 0.114 4 0.486 4 4 0.886 0.686 4 0.486 0.486 4 [ 0.884 4 | 4 0.343 0.486 4 0.886 0.343 40 4 0.200 0.200 4 0.686 0.029 4 [ 0.054 4 | 4 0.114 0.057 4 0.486 0.029 4 \ 0.343 | 4 4 0.686 0.686 4 0.343 0.200 4 | 1.000 | 4 4 0.114 0.486 4 0.114 0.057 4 | 0 .200| 4| | 4 0.057 0.486 4 0.200 0.200 4 \ 0.343 | 4 4 0.200 0.343 4 0.343 1.000 4 \ 0.486 4 4 0.343 0.686 4 1.000 1.000 4 [ 1.004 4 | 4 0.343 1.000 4 0.343 0.343 4 | 0.343 | 4 4 0.343 0.200 4 0.114 0.200 4 [ 0.884 4 | 4 0.686 0.486 4 0.486 0.686 4 | 0.886 | 4 4 0.886 0.200 4 0.114 1.000 4 | 0.686 | 4 4 0.886 0.886 4 1.000 0.886 4 [ 0.484 4 | 4 0.486 0.686 4 0.886 1.000 4 | 0.886 | 4 4 0.200 0.886 4 0.200 0.343 4 [ 0.684 4 | 4 0.114 0.200 4 0.886 0.200 4 | 0.343 | 4 4 0.114 0.686 4 0.057 0.200 4 | 0.114 | 4 4 0.057 0.686 4 0.200 0.200 4 [ 0.484 4 | 4 0.200 0.686 4 0.486 1.000 4 | 0.486 | 4 4 0.114 0.886 4 0.686 0.886 4 [ 0.684 4 | 4 0.886 4 I 0.486 I 4 4 0.114 1.000 4 0.114 4 0.886 0.886 0.886 0.200 I I p<0 05 I Page A49 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 D6. Energy expenditure Tim e (hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 M e ta b o lic c a g e s g ro u p 1: H F c o n tro l E nergy expenditure (kcal/h/kg m ouse) A v e ra g e e n e rg y e x p e n d itu re cage 0101 cage 0105 cage 0201 cage 0205 (k c a l/h /k g m o u se) 15.26 17.60 18.09 15.65 1 6 .6 5 14.77 18.58 16.69 14.83 1 6 .2 2 14.06 17.22 15.46 15.02 1 5 .4 4 15.29 17.23 18.03 14.38 1 6 .2 3 13.87 15.56 14.51 15.73 1 4 .9 2 14.09 14.71 16.01 14.24 1 4 .7 6 13.11 15.06 13.84 13.08 1 3 .7 7 13.48 13.36 13.89 13.27 1 3 .5 0 12.13 13.82 13.73 13.00 1 3 .1 7 14.07 15.59 13.01 13.78 14.23 12.86 13.37 13.16 1 3 .6 7 1 3 .8 5 13.62 12.84 14.11 14.44 14.61 12.93 14.87 12.21 1 4 .3 0 1 3 .1 1 13.44 13.08 14.15 14.04 1 3 .6 8 14.61 14.60 14.57 13.58 1 4 .3 4 18.76 18.08 18.68 19.18 1 8 .6 7 14.71 16.46 17.67 18.47 1 6 .8 3 16.80 17.25 17.38 14.72 1 6 .5 4 14.60 15.94 17.12 17.36 1 6 .2 5 14.85 15.69 15.70 14.61 1 5 .2 1 14.90 15.61 16.65 14.99 1 5 .5 4 13.70 15.30 16.48 15.57 1 5 .2 6 13.66 15.14 16.64 13.85 1 4 .8 2 15.51 14.87 15.70 13.65 1 4 .9 3 13.93 14.80 13.31 13.10 1 3 .7 8 13.90 14.00 16.10 13.12 1 4 .2 8 13.43 12.20 12.69 13.39 14.25 14.13 12.34 13.03 1 3 .1 8 1 3 .1 9 13.65 13.20 13.31 11.93 1 3 .0 2 11.75 13.71 13.91 13.69 1 3 .2 7 12.71 12.39 13.16 12.74 1 2 .7 5 12.64 13.18 14.44 12.48 1 3 .1 9 13.72 14.15 14.99 13.38 1 4 .0 6 14.48 14.15 13.45 13.61 1 3 .9 3 17.69 17.46 18.78 16.77 1 7 .6 7 16.95 16.08 18.41 16.32 1 6 .9 4 16.37 17.06 17.66 15.18 1 6 .5 7 14.77 16.94 16.72 15.37 1 5 .9 5 14.41 15.64 15.92 15.35 1 5 .3 3 14.84 15.90 16.22 14.90 1 5 .4 6 13.10 15.64 15.87 13.62 1 4 .5 6 13.93 15.75 16.27 14.08 1 5 .0 1 13.93 13.92 16.08 14.73 1 4 .6 7 14.30 15.21 15.35 12.69 1 4 .3 9 13.41 13.41 13.86 12.72 1 3 .3 5 11.94 14.05 13.54 11.28 1 2 .7 0 12.07 13.53 12.94 12.28 14.22 14.41 12.19 11.88 1 2 .8 6 1 3 .0 2 11.78 10.77 11.51 12.25 1 1 .5 8 12.67 12.95 13.74 11.51 1 2 .7 2 11.52 12.61 12.64 12.73 1 2 .3 7 12.09 12.89 12.94 11.99 1 2 .4 8 12.71 11.98 13.88 13.18 1 2 .9 4 15.29 15.54 16.61 15.93 1 5 .8 4 16.15 17.21 19.20 16.67 1 7 .3 1 16.12 16.43 17.30 16.02 1 6 .4 7 14.28 15.90 16.75 14.24 1 5 .2 9 14.01 16.21 16.58 15.16 1 5 .4 9 SD 1.4 0 1 .8 1 1.3 2 1.6 9 0.8 8 0.8 8 0.9 3 0.2 7 0.7 8 0.5 8 1.2 2 0.5 6 0.9 5 0 .5 1 0.5 0 0.4 5 1.6 4 1.2 4 1.2 7 0.5 7 0.8 0 1.1 6 1.3 8 0.9 3 0.7 6 1.2 8 0.8 4 0.8 0 0.7 5 1 .0 1 0.3 2 0.8 9 0.7 0 0.4 8 0.8 4 1.0 5 1.0 6 1.0 5 0.6 6 0.7 0 1.4 0 1.1 8 1.0 2 1.2 2 0.4 7 1 .3 1 0.9 9 1.1 6 0.6 2 0.9 2 0.5 7 0 .5 1 0.8 0 0.5 7 1.3 3 0.5 8 1.2 4 1.1 6 Tim e (hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 M etabolic cages group 3: HF + 0.03 % PFBS E nergy expenditure (kcal/h/kg m ouse) A v e ra g e e n e rg y e x p e n d itu re cage 0102 cage 0106 cage 0202 cage 0206 (k c a l/h /k g m o u se) 17.43 16.55 15.54 17.20 1 6 .6 8 17.09 16.86 16.94 17.80 1 7 .1 7 15.39 15.70 17.29 16.16 1 6 .1 3 15.91 14.45 15.57 16.99 1 5 .7 3 16.34 15.43 18.84 15.42 1 6 .5 1 14.64 15.03 16.85 14.16 1 5 .1 7 15.19 12.93 15.35 15.09 1 4 .6 4 13.95 13.93 15.14 12.27 1 3 .8 2 14.44 13.92 16.41 12.52 1 4 .3 2 14.01 12.76 17.22 13.38 1 4 .3 4 14.98 14.58 15.00 12.81 1 4 .3 4 12.72 13.02 15.40 12.07 1 3 .3 0 13.81 13.65 16.90 13.71 1 4 .5 2 13.46 14.25 15.08 13.72 1 4 .1 3 15.62 12.57 17.30 13.56 1 4 .7 6 18.75 18.37 20.52 17.56 1 8 .8 0 18.06 19.16 19.87 18.43 1 8 .8 8 16.48 15.80 17.65 17.88 1 6 .9 5 16.92 12.95 16.88 15.09 1 5 .4 6 15.90 14.09 16.54 12.21 17.00 17.31 16.45 15.23 1 6 .4 7 1 4 .7 1 14.12 13.77 17.36 14.77 1 5 .0 0 14.78 12.74 16.24 13.97 1 4 .4 3 15.12 13.05 16.89 15.06 1 5 .0 3 14.52 15.83 14.64 12.02 16.12 16.36 13.22 14.18 1 4 .6 2 1 4 .6 0 13.76 13.81 12.26 12.37 15.82 15.88 12.58 12.21 1 3 .6 1 1 3 .5 7 13.39 12.95 15.06 12.52 1 3 .4 8 13.12 10.84 16.01 15.10 1 3 .7 7 13.64 11.69 15.73 13.03 1 3 .5 2 13.95 12.08 16.21 13.22 1 3 .8 6 13.47 12.78 15.51 12.95 1 3 .6 8 15.18 12.38 16.46 13.52 1 4 .3 9 17.57 15.45 18.91 17.72 1 7 .4 1 19.09 17.24 18.98 18.82 1 8 .5 3 17.30 16.92 17.99 17.07 1 7 .3 2 16.05 14.75 16.27 16.18 1 5 .8 1 16.77 13.77 16.86 15.23 1 5 .6 6 15.50 14.08 17.30 15.96 1 5 .7 1 15.48 14.73 16.46 15.33 1 5 .5 0 14.11 13.92 16.45 15.71 1 5 .0 5 15.24 15.13 17.39 15.86 1 5 .9 1 14.87 13.68 16.69 14.54 1 4 .9 4 13.37 15.05 14.93 12.60 1 3 .9 9 12.14 13.59 14.17 13.05 1 3 .2 4 11.67 13.16 14.32 11.27 1 2 .6 0 11.45 11.64 15.69 13.95 1 3 .1 8 12.32 11.54 11.23 11.21 13.41 14.36 11.25 13.65 1 2 .0 5 1 2 .6 9 11.90 12.82 13.42 11.92 1 2 .5 2 11.77 11.55 13.71 11.82 1 2 .2 1 13.05 11.30 15.86 13.56 1 3 .4 4 15.71 14.02 16.76 15.30 1 5 .4 4 17.40 15.88 19.87 17.20 1 7 .5 9 15.92 16.23 17.67 16.87 1 6 .6 8 15.41 14.16 16.82 16.69 1 5 .7 7 14.65 14.28 17.27 16.29 1 5 .6 2 SD 0 .85 0 .43 0 .83 1 .0 5 1 .6 1 1 .1 7 1 .1 4 1 .1 8 1 .6 1 1 .9 9 1 .0 4 1 .4 5 1 .5 9 0 .72 2 .12 1 .2 5 0 .80 0 .98 1 .8 8 0 .45 2 .13 1 .6 2 1 .4 7 1 .5 7 1 .1 9 1 .9 5 1 .6 1 1 .7 0 1 .1 1 2 .29 1 .6 8 1 .7 4 1 .2 5 1 .7 9 1 .4 4 0 .87 0 .48 0 .7 1 1 .4 6 1 .3 3 0 .72 1 .2 3 1 .0 4 1 .2 7 1 .2 0 0 .86 1 .4 0 2 .02 1 .0 4 1 .5 5 0 .74 1 .0 0 1 .8 8 1 .1 3 1 .6 7 0 .77 1 .2 5 1 .4 0 Page A50 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Tim e (hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 M etabolic cages group 4: HF + 0.006 % PFHS Energy expenditure (kcal/h/kg m ouse) A v e ra g e en erg y exp e n d itu re cage 0103 cage 0107 cage 0203 cage 0207 (kcal/h /kg m o u s e ) 17.72 18.32 18.90 18.10 1 8 .2 6 17.11 17.10 18.69 17.78 1 7 .6 7 16.08 17.64 18.56 15.91 1 7 .0 5 16.29 16.21 18.34 14.84 1 6 .4 2 15.79 14.83 18.65 16.03 1 6 .3 3 15.90 16.76 18.05 16.46 1 6 .7 9 15.81 13.50 15.81 14.17 1 4 .8 2 15.50 14.04 16.75 14.00 1 5 .0 7 15.27 16.11 15.26 13.82 1 5 .1 2 15.08 15.83 15.47 13.59 1 4 .9 9 14.56 14.33 14.50 14.54 1 4 .4 8 14.82 15.78 15.58 14.07 1 5 .0 6 15.26 14.93 14.36 13.74 1 4 .5 7 14.90 14.62 15.33 16.29 1 5 .2 8 15.70 15.43 15.87 14.86 1 5 .4 6 19.72 20.61 21.15 20.63 18.58 20.66 17.89 20.08 1 9 .3 3 2 0 .5 0 18.46 19.15 18.98 18.45 1 8 .7 6 17.40 16.86 19.80 18.59 1 8 .1 6 15.63 17.63 18.26 16.07 1 6 .9 0 16.78 15.69 18.33 15.98 1 6 .6 9 15.19 14.09 19.84 16.07 1 6 .2 9 15.21 15.71 19.30 15.97 1 6 .5 5 14.31 11.67 17.68 14.78 1 4 .6 1 15.18 14.05 16.54 15.91 1 5 .4 2 14.73 15.03 17.36 15.56 1 5 .6 7 14.63 13.86 15.71 12.89 1 4 .2 7 13.99 13.36 14.92 14.30 1 4 .1 4 14.49 14.67 15.65 12.34 1 4 .2 9 14.01 13.51 14.35 13.17 1 3 .7 6 14.08 13.28 14.29 13.21 1 3 .7 1 13.47 14.84 16.71 12.78 1 4 .4 5 14.88 16.08 15.00 15.51 1 5 .3 7 15.64 14.14 16.17 13.12 1 4 .7 7 18.28 20.86 17.34 19.42 17.39 20.34 15.11 17.84 1 7 .0 3 1 9 .6 2 18.77 18.11 21.60 18.16 1 9 .1 6 18.37 16.76 19.49 18.59 1 8 .3 0 17.30 17.80 19.21 16.43 1 7 .6 8 16.46 14.44 18.06 16.42 1 6 .3 5 16.08 15.13 17.28 16.52 1 6 .2 5 14.64 14.47 18.02 14.88 1 5 .5 0 15.67 15.08 17.87 15.07 1 5 .9 2 14.27 12.31 16.74 14.16 1 4 .3 7 14.48 12.77 15.72 13.40 1 4 .0 9 14.56 13.88 13.63 12.02 14.62 15.96 13.60 12.96 1 4 .1 1 1 3 .7 0 13.99 13.95 14.50 12.77 1 3 .8 0 12.49 11.40 15.11 14.61 1 3 .4 0 13.11 12.66 11.93 12.96 14.36 14.99 12.75 12.77 1 3 .0 4 1 3 .3 5 13.64 13.88 14.56 13.32 1 3 .8 5 13.62 14.26 14.77 12.59 1 3 .8 1 15.79 15.84 15.90 14.20 1 5 .4 3 18.77 19.12 18.49 16.54 1 8 .2 3 19.64 17.74 21.04 18.51 1 9 .2 3 16.81 14.27 20.24 17.03 1 7 .0 9 16.94 15.58 19.19 16.40 1 7 .0 3 SD 0 .4 9 0 .7 5 1 .2 7 1 .4 4 1 .6 4 0 .9 1 1 .1 7 1 .3 2 0 .9 5 0 .9 9 0 .1 1 0 .7 8 0 .6 7 0 .7 3 0 .4 4 1 .4 3 0 .2 8 0 .3 6 1.31 1 .2 5 1 .1 8 2 .5 0 1 .8 6 2 .4 6 1 .0 7 1 .1 8 1 .2 0 0 .6 5 1 .3 9 0 .5 2 0 .5 5 1 .7 3 0 .5 5 1 .4 0 1 .3 5 1 .3 3 1 .6 5 1 .1 4 1 .1 6 1 .4 8 0 .9 0 1 .6 9 1 .3 3 1 .8 2 1 .3 0 0 .5 6 1 .6 9 0 .7 3 1 .7 5 1.01 1 .1 0 0 .5 3 0 .9 4 0 .8 2 1 .1 6 1 .4 3 2 .4 5 1 .5 5 Tim e (hr) 6.1 7.4 8.6 9.9 11.1 12.4 13.6 14.9 16.1 17.4 18.6 19.9 21.1 22.4 23.6 24.9 26.1 27.4 28.6 29.9 31.1 32.4 33.6 34.9 36.1 37.4 38.6 39.9 41.1 42.4 43.6 44.9 46.1 47.4 48.6 49.9 51.1 52.4 53.6 54.9 56.1 57.4 58.6 59.9 61.1 62.4 63.6 64.9 66.1 67.4 68.6 69.9 71.1 72.4 73.6 74.9 76.1 77.4 M etabolic cages group 6: HF + 0.003 % PFO S Energy expenditure (kcal/h/kg m ouse) A v e ra g e en erg y exp e n d itu re cage 0104 cage 0108 cage 0204 cage 0208 (k c a l/h /k g m o u s e ) 19.47 21.08 19.61 17.81 1 9 .4 9 18.62 19.06 18.86 18.04 1 8 .6 5 16.51 18.30 18.11 16.54 1 7 .3 6 18.20 18.49 17.62 16.84 1 7 .7 9 19.01 17.84 18.00 15.43 1 7 .5 7 17.93 15.57 16.43 15.19 1 6 .2 8 18.49 14.69 15.83 15.23 1 6 .0 6 17.61 16.67 15.79 14.34 1 6 .1 0 16.12 13.87 14.75 14.73 1 4 .8 7 15.64 15.29 14.35 13.23 1 4 .6 3 18.32 17.05 15.27 13.96 1 6 .1 5 17.91 14.12 13.69 14.47 1 5 .0 5 16.01 15.24 14.26 14.58 1 5 .0 2 15.85 16.13 14.28 14.54 1 5 .2 0 18.23 20.12 15.33 19.45 14.68 16.14 15.49 16.60 1 5 .9 3 1 8 .0 8 21.17 19.41 19.46 18.32 1 9 .5 9 18.52 18.96 20.24 19.23 1 9 .2 4 19.45 20.08 17.71 18.51 1 8 .9 4 18.39 17.21 16.81 16.76 1 7 .2 9 19.29 17.83 17.23 16.41 1 7 .6 9 18.53 15.12 16.72 16.89 1 6 .8 1 18.69 16.53 17.36 15.99 1 7 .1 4 18.84 16.51 16.59 15.65 1 6 .9 0 18.59 14.60 15.98 14.62 1 5 .9 5 17.62 14.68 16.18 15.30 1 5 .9 4 16.44 14.48 14.14 15.27 1 5 .0 8 16.15 12.94 14.29 15.48 1 4 .7 2 15.21 13.64 14.29 14.75 1 4 .4 7 15.50 15.37 13.42 14.02 1 4 .5 8 15.94 13.52 15.32 15.22 1 5 .0 0 16.36 13.59 14.18 14.09 1 4 .5 6 16.01 14.15 14.92 14.94 1 5 .0 0 16.00 14.11 14.52 14.85 1 4 .8 7 18.97 21.66 15.99 18.42 17.26 17.93 15.91 17.63 1 7 .0 3 1 8 .9 1 18.81 19.72 18.76 18.78 1 9 .0 2 19.91 19.11 17.76 17.42 1 8 .5 5 18.13 18.31 17.13 17.61 1 7 .7 9 19.04 16.79 16.98 16.20 1 7 .2 5 19.21 15.17 17.38 16.28 1 7 .0 1 18.16 16.35 17.05 16.49 1 7 .0 1 18.42 16.12 16.12 16.24 1 6 .7 3 18.84 16.11 16.36 16.05 1 6 .8 4 17.44 15.08 15.28 15.33 1 5 .7 8 17.66 15.22 14.46 15.22 1 5 .6 4 15.27 13.11 14.82 13.76 1 4 .2 4 15.52 14.03 13.04 14.49 1 4 .2 7 14.25 12.15 13.77 13.48 1 3 .4 1 15.72 15.34 14.09 12.66 13.50 13.55 12.84 13.02 1 4 .0 4 1 3 .6 4 15.08 14.14 12.63 14.25 1 4 .0 2 14.87 13.67 12.91 13.09 1 3 .6 4 17.36 13.95 14.19 14.87 1 5 .0 9 18.36 17.87 15.30 15.80 1 6 .8 3 18.82 16.27 16.93 17.77 1 7 .4 5 17.86 17.62 16.97 18.62 1 7 .7 6 18.01 17.66 16.20 17.84 1 7 .4 3 SD 1 .3 4 0 .44 0 .97 0 .73 1 .5 2 1 .2 2 1 .6 8 1 .3 9 0 .93 1 .0 8 1 .9 2 1 .9 4 0 .78 0 .93 1 .5 7 2 .00 1 .1 8 0 .73 1 .0 4 0 .76 1 .2 2 1 .3 9 1 .1 8 1 .3 6 1 .8 8 1 .2 7 1 .0 2 1 .4 1 0 .67 1 .0 2 1 .0 4 1 .2 3 0 .76 0 .8 1 1 .4 3 1 .8 6 0 .47 1 .1 6 0 .53 1 .2 4 1 .7 2 0 .82 1 .1 3 1 .3 4 1 .1 1 1 .3 9 0 .98 1 .0 3 0 .90 1 .2 3 1 .1 9 1 .0 2 0 .89 1 .5 6 1 .5 1 1 .1 0 0 .68 0 .83 Page A51 of A172 Appendix to TNO-report of 3M-02_____________ Final version Time group 1 vs 3 (hr) n n p 6.1 4 4 0.886 7.4 4 4 0.343 8.6 4 4 0.343 9.9 4 4 0.886 11.1 4 4 0.343 12.4 4 4 0.686 13.6 4 4 0.343 14.9 4 4 0.343 16.1 4 4 0.200 17.4 4 4 1.000 18.6 4 4 0.886 19.9 4 4 0.343 21.1 4 4 0.200 22.4 4 4 0.343 23.6 4 4 1.000 24.9 4 4 0.886 26.1 4 4 0.114 27.4 4 4 0.686 28.6 4 4 0.486 29.9 4 4 0.029 31.1 4 4 0.686 32.4 4 4 0.886 33.6 4 4 0.886 34.9 4 4 1.000 36.1 4 4 0.486 37.4 4 4 0.686 38.6 4 4 1.000 39.9 4 4 0.886 41.1 4 4 0.886 42.4 4 4 0.886 43.6 4 4 0.486 44.9 4 4 0.686 46.1 4 4 0.486 47.4 4 4 0.886 48.6 4 4 0.886 49.9 4 4 0.057 51.1 4 4 0.343 52.4 4 4 0.686 53.6 4 4 0.886 54.9 4 4 0.886 56.1 4 4 0.686 57.4 4 4 1.000 58.6 4 4 0.200 59.9 4 4 0.886 61.1 4 4 0.886 62.4 4 4 0.486 63.6 4 4 0.886 64.9 4 4 0.886 66.1 4 4 0.686 67.4 4 4 1.000 68.6 4 4 0.686 69.9 4 4 0.343 71.1 4 4 0.886 72.4 4 4 0.886 73.6 4 4 0.886 74.9 4 4 0.886 76.1 4 4 0.886 77.4 4 4 0.886 gr n 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 aEnergy expenditure p-values Mann Whitney U-test group 1 vs 6 group 3 vs 4 group 3 vs 6 group 4 vs 6 p n p nn p 0.057 0.057 4 0.029 4 0.029 0.200 0.200 0.057 4 0.200 4 0.029 0.114 0.114 0.114 4 0.343 4 0.114 0.686 0.886 0.200 4 0.486 4 0.057 0.200 0.114 0.114 4 0.886 4 0.343 0.486 0.057 0.114 4 0.200 4 0.200 0.343 0.200 0.057 4 0.686 4 0.343 0.343 0.029 0.029 4 0.114 4 0.057 0.343 0.029 0.029 4 0.686 4 0.686 0.886 0.114 0.200 4 0.486 4 0.686 0.686 0.343 0.114 4 0.343 4 0.200 0.343 0.343 0.886 4 0.114 4 0.200 0.686 0.114 0.057 4 0.486 4 0.343 0.686 0.029 0.029 4 0.114 4 0.114 0.686 0.029 0.029 4 0.686 4 0.686 0.886 0.886 1.000 4 0.686 4 0.686 0.486 0.029 0.057 4 0.029 4 0.486 0.343 0.029 0.029 4 0.029 4 0.029 0.343 0.114 0.029 4 0.114 4 0.029 0.486 0.114 0.029 4 0.886 4 0.114 0.686 0.114 0.057 4 0.200 4 0.114 0.343 0.886 0.200 4 0.486 4 0.200 0.686 0.200 0.114 4 0.200 4 0.057 0.343 0.686 0.057 4 0.686 4 0.200 0.200 0.057 0.114 4 0.486 4 0.486 0.886 0.200 0.114 4 0.686 4 0.486 0.886 0.200 0.057 4 0.486 4 0.200 0.486 0.200 0.200 4 0.486 4 0.343 0.686 0.200 0.057 4 0.486 4 0.200 1.000 0.686 0.200 4 0.686 4 0.686 0.343 0.029 0.029 4 1.000 4 0.343 0.114 0.200 0.200 4 0.686 4 0.343 0.886 0.057 0.200 4 0.686 4 0.200 0.486 0.686 0.114 4 0.114 4 0.886 1.000 0.486 0.486 4 0.886 4 0.886 0.886 0.057 0.114 4 0.486 4 0.886 0.686 0.029 0.029 4 0.200 4 0.029 0.486 0.057 0.029 4 0.029 4 0.029 0.886 0.029 0.029 4 0.114 4 0.029 0.886 0.343 0.057 4 0.486 4 0.200 0.486 0.114 0.114 4 0.343 4 0.343 0.486 0.686 0.029 4 0.686 4 0.057 0.200 0.200 0.029 4 0.686 4 0.200 0.200 0.686 0.029 4 0.686 4 0.200 0.210 0.686 0.029 4 0.886 4 0.029 0.200 0.114 0.029 4 0.114 4 0.029 0.114 0.686 0.114 4 0.486 4 0.200 0.686 0.343 0.200 4 0.486 4 0.486 0.486 0.200 0.057 4 0.200 4 0.114 0.886 0.686 0.200 4 0.686 4 0.486 0.343 0.057 0.057 4 0.486 4 0.200 0.486 0.029 0.114 4 0.114 4 0.057 0.686 0.343 0.486 4 0.686 4 0.886 1.000 0.686 0.343 4 0.686 4 0.686 0.486 0.686 0.686 4 0.686 4 0.686 0.114 0.029 0.200 4 0.029 4 0.200 0.200 0.200 0.029 4 0.343 4 0.029 0.486 0.200 0.114 4 0.343 4 0.114 0.686 04-12-2006 p<0.05 Page A52 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Appendix E. Fecal bile acid, sterol and fatty acid measurements E1. Fecal weight measurements, bodyweight and food intake measurements Bodyweight and food intake during collecting feces Group# Mouse# cage# 11 21 32 42 53 63 74 85 95 10 5 2 11 6 2 12 6 2 13 6 2 14 7 2 15 8 2 16 8 2 17 8 2 18 9 2 19 9 2 20 10 3 21 11 3 22 12 3 23 13 3 24 13 3 25 14 3 26 15 3 27 15 3 28 15 13 29 16 3 30 17 31 18 32 18 33 19 34 19 35 19 36 19 37 20 38 20 39 21 40 21 5 41 22 5 42 22 5 43 22 5 44 22 5 45 23 5 46 24 5 47 25 5 48 25 5 49 26 5 50 27 6 51 28 6 52 29 6 53 29 6 54 30 6 55 30 6 56 31 6 57 31 6 58 31 6 59 31 6 60 32 7 61 33 7 62 34 7 63 35 7 64 36 7 65 36 7 66 37 7 67 38 7 68 38 7 69 39 7 70 39 collection point 1;2daysfecescollection eartag startcollectionpoint 1 endcollection point 1 Average Foodintake(g) L R bodyweight (g) foodoncage(g) bodyweight (g) foodoffcage(g) bodyweight(g) coll. point 1 0 1 33.9 33.9 33.90 1 2 31.2 49.7 30.5 38.9 30.85 10.8 0 0 30.4 31.0 30.70 2 0 28.1 51.9 28.2 39.5 28.15 12.4 0 0 31.1 30.6 30.85 0 2 29.5 47.4 29.4 35.8 29.45 11.6 1 1 26.7 26.9 27.2 20.5 26.95 6.4 0 0 30.4 30.6 30.50 0 2 30.6 31.0 30.80 1 2 27.2 61.6 27.3 44.8 27.25 16.8 1 0 33.0 33.1 33.05 2 1 29.8 30.0 29.90 0 2 31.2 68.5 32.0 48.6 31.60 19.9 0 1 32.8 31.7 33.1 24.8 32.95 6.9 1 0 30.8 31.0 30.90 0 1 30.1 29.8 29.95 2 0 32.8 68.0 32.8 47.2 32.80 20.8 0 0 26.5 26.6 26.55 2 1 26.9 42.3 26.6 31.8 26.75 10.5 1 0 29.0 29.2 28.8 23.4 28.90 5.8 0 1 27.8 32.1 28.3 26.2 28.05 5.9 0 2 28.8 32.9 28.9 27.2 28.85 5.7 0 1 32.2 32.3 32.25 1 1 28.8 44.9 28.9 30.3 28.85 14.6 1 0 25.8 31.2 26.3 25.2 26.05 6.0 0 1 28.7 28.5 28.60 2 0 30.1 30.1 30.10 1 2 25.0 77.5 24.7 61.0 24.85 16.5 0 2 29.8 23.1 29.7 17.1 29.75 6.0 1 0 27.0 26.3 27.0 20.0 27.00 6.3 1 0 30.3 30.2 30.25 0 2 29.3 48.3 29.2 36.3 29.25 12.0 0 0 29.2 28.9 29.05 1 0 30.9 30.7 30.80 0 1 31.0 30.7 30.85 0 2 25.6 90.1 25.8 68.4 25.70 21.7 0 0 27.0 26.7 26.85 1 1 30.2 43.1 30.2 31.0 30.20 12.1 0 0 27.7 27.2 27.45 1 1 27.7 47.9 27.7 36.0 27.70 11.9 1 0 28.9 30.0 29.45 0 1 25.2 25.3 25.25 1 1 27.6 27.8 27.70 1 2 28.5 90.3 28.1 68.8 28.30 21.5 1 2 28.6 37.8 29.7 30.8 29.15 7.0 2 0 28.5 27.2 28.6 21.1 28.55 6.1 0 1 30.3 30.1 30.20 1 1 29.3 50.7 29.9 37.2 29.60 13.5 0 0 27.3 27.7 27.2 22.1 27.25 5.6 1 2 27.7 27.1 28.7 20.2 28.20 6.9 0 1 28.4 31.9 28.5 26.2 28.45 5.7 1 0 31.3 31.5 31.40 1 2 27.3 52.3 27.2 40.4 27.25 11.9 1 0 30.2 30.0 30.10 0 2 28.8 42.9 28.4 31.2 28.60 11.7 0 0 25.6 25.4 25.50 0 1 27.6 27.8 27.70 0 2 29.1 29.1 29.10 2 2 30.3 88.0 30.7 67.7 30.50 20.3 2 1 26.7 30.5 26.7 25.0 26.70 5.5 2 0 28.2 29.1 27.7 23.4 27.95 5.7 1 0 27.3 31.2 26.7 25.5 27.00 5.7 0 2 26.2 34.7 26.6 29.3 26.40 5.4 0 0 28.2 28.5 28.35 1 2 27.4 21.2 28.2 9.4 27.80 11.8 0 0 26.1 26.4 26.1 21.3 26.10 5.1 0 0 26.0 26.2 26.10 2 0 26.7 53.0 26.9 42.5 26.80 10.5 1 0 23.6 23.0 23.30 0 1 25.1 43.8 24.6 32.4 24.85 11.4 Page A53 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 G roup# M ouse# cage# 11 21 32 42 53 63 74 85 95 10 5 2 11 6 2 12 6 2 13 6 2 14 7 2 15 8 2 16 8 2 17 8 2 18 9 2 19 9 2 20 10 3 21 11 3 22 12 3 23 13 3 24 13 3 25 14 3 26 15 3 27 15 3 28 15 13 29 16 3 30 17 31 18 32 18 33 19 34 19 35 19 36 19 37 20 38 20 39 21 40 21 5 41 2 2 5 42 22 5 43 22 5 44 22 5 45 23 5 46 24 5 47 25 5 48 25 5 49 26 5 50 27 6 51 2 8 6 52 29 6 53 29 6 54 30 6 55 30 6 56 31 6 57 31 6 58 31 6 59 31 6 60 32 7 61 3 3 7 62 34 7 63 35 7 64 36 7 65 36 7 66 37 7 67 38 7 68 38 7 69 39 7 70 39 e a rta g LR 01 12 00 20 00 02 11 00 02 12 10 21 02 01 10 01 20 00 21 10 01 02 01 11 10 01 20 12 02 10 10 02 00 10 01 02 00 11 00 11 10 01 11 12 12 20 01 11 00 12 01 10 12 10 02 00 01 02 22 21 20 10 02 00 12 00 00 20 10 01 co lle c tio n p oint 2; 3 days fe c e s co lle ctio n sta rt c o lle ctio n p oint 2 end c o lle ctio n point 2 bod yw e ig h t (g) fo o d on ca g e (g) bod yw e ig h t (g) fo o d o ff ca g e (g) 3 3 .9 3 0 .5 3 8 .9 3 2 .9 30.1 22.1 31 30 2 8 .2 3 9 .5 2 8 .3 19.5 3 0 .6 2 9 .2 2 9 .4 3 5 .8 3 0 .4 16.8 2 7 .2 3 0 .6 2 0 .5 2 6 .3 30 10.7 31 2 7 .3 4 4 .8 3 0 .5 27 19.2 33.1 3 2 .2 30 30 32 48.6 31.2 19.8 33.1 2 4 .8 3 3 .6 1 2 .4 31 2 9 .8 30.1 30 3 2 .8 4 7 .2 3 2 .5 14.2 2 6 .6 2 6 .3 2 6 .6 2 8 .8 3 1 .8 2 3 .4 2 6 .9 29 13.6 1 3 .4 2 8 .3 2 6 .2 2 8 .4 15.7 2 8 .9 2 7 .2 2 9 .2 16.2 3 2 .3 2 8 .9 3 0 .3 3 2 .3 2 9 .2 7.1 2 6 .3 2 8 .5 2 5 .2 26.1 2 8 .8 15.6 30.1 2 9 .8 2 4 .7 2 9 .7 6 1 .0 17.1 25.1 2 9 .4 3 2 .7 8.0 27 20.0 27.6 9.4 3 0 .2 2 9 .6 2 9 .2 3 6 .3 2 8 .7 16.5 2 8 .9 3 0 .7 2 9 .6 3 0 .5 3 0 .7 3 0 .7 2 5 .8 6 8 .4 2 6 .2 3 3 .2 2 6 .7 2 6 .9 3 0 .2 3 1 .0 30.1 11.1 2 7 .2 2 7 .7 3 6 .0 2 7 .2 2 7 .7 17.7 30 2 5 .3 29.1 2 5 .5 2 7 .8 2 8 .6 28.1 2 9 .7 6 8 .8 3 0 .8 2 8 .8 30.1 3 2 .3 20.1 2 8 .6 21.1 2 8 .6 10.6 30.1 2 9 .9 3 7 .2 30.1 2 9 .7 15.5 2 7 .2 2 8 .7 22.1 2 0 .2 27 2 8 .4 12.5 10.2 2 8 .5 2 6 .2 2 8 .7 16.6 3 1 .5 2 7 .2 4 0 .4 3 1 .4 27 2 0 .3 30 29.7 2 8 .4 3 1 .2 28 12.3 2 5 .4 2 5 .3 2 7 .8 29.1 2 6 .9 2 8 .8 3 0 .7 6 7 .7 3 0 .9 3 6 .7 2 6 .7 2 5 .0 2 6 .3 16.0 2 7 .7 2 3 .4 29.1 12.7 2 6 .7 2 5 .5 2 7 .8 16.3 2 6 .6 2 8 .5 2 9 .3 2 6 .8 2 8 .9 2 0 .0 2 8 .2 26.1 56.1 2 1 .3 2 7 .6 2 6 .2 3 8 .8 12.1 2 6 .2 2 6 .7 2 6 .9 23 2 4 .6 4 2 .5 3 2 .4 2 7 .2 2 3 .6 2 5 .7 2 4 .9 15.0 A verage b o d yw e ig h t (g) 3 3 .4 0 3 0 .3 0 3 0 .5 0 2 8 .2 5 2 9 .9 0 2 9 .9 0 2 6 .7 5 3 0 .3 0 3 0 .7 5 2 7 .1 5 3 2 .6 5 3 0 .0 0 3 1 .6 0 3 3 .3 5 3 0 .5 5 2 9 .9 0 3 2 .6 5 2 6 .4 5 2 6 .7 5 2 8 .9 0 2 8 .3 5 2 9 .0 5 3 2 .3 0 2 9 .0 5 2 6 .2 0 2 8 .6 5 2 9 .9 5 2 4 .9 0 2 9 .5 5 2 7 .3 0 2 9 .9 0 2 8 .9 5 2 9 .2 5 3 0 .6 0 3 0 .7 0 2 6 .0 0 2 6 .8 0 3 0 .1 5 2 7 .2 0 2 7 .7 0 2 9 .5 5 2 5 .4 0 2 8 .2 0 2 8 .4 5 2 9 .9 0 2 8 .6 0 3 0 .1 0 2 9 .8 0 2 7 .1 0 2 8 .5 5 2 8 .6 0 3 1 .4 5 2 7 .1 0 2 9 .8 5 2 8 .2 0 2 5 .3 5 2 7 .3 5 2 8 .9 5 3 0 .8 0 2 6 .5 0 2 8 .4 0 2 7 .2 5 2 6 .7 0 2 8 .7 0 2 7 .9 0 2 6 .1 5 2 6 .4 5 2 7 .0 5 2 3 .3 0 2 5 .1 5 F oo d in take (g) coll. p o in t 2 1 6 .8 2 0 .0 1 9 .0 9.8 2 5 .6 2 8 .8 1 2 .4 3 3 .0 1 8 .2 10.0 1 0 .5 1 1 .0 2 3 .2 9.6 2 8 .3 9.1 10.6 1 9 .8 3 5 .2 1 9 .9 18.3 3 6 .5 1 0 .7 1 0 .5 2 1 .7 9.6 10.0 9.6 20.1 1 8 .9 3 1 .0 9.0 1 0 .7 9.2 9.3 1 7 .3 9.2 1 7 .6 1 7 .4 Page A54 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 G roup# M ouse# cage# 111 12 1 13 2 14 2 15 3 16 3 17 4 18 5 19 5 1 10 5 2 11 6 2 12 6 2 13 6 2 14 7 2 15 8 2 16 8 2 17 8 2 18 9 2 19 9 2 20 10 3 21 11 3 22 12 3 23 13 3 24 13 3 25 14 3 26 15 3 27 15 3 28 15 13 29 16 3 30 17 31 18 32 18 33 19 34 19 35 19 36 19 37 20 38 20 3 9 21 4 0 21 5 41 22 5 42 22 5 43 22 5 44 22 5 45 23 5 46 24 5 47 25 5 48 25 5 49 26 5 50 27 6 51 28 6 52 29 6 53 29 6 54 30 6 55 30 6 5 6 31 6 57 31 6 5 8 31 6 5 9 31 6 60 32 7 61 33 7 62 34 7 63 35 7 64 36 7 65 36 7 66 37 7 67 38 7 68 38 7 69 39 7 70 39 eartag LR 01 12 00 20 00 02 11 00 02 12 10 21 02 01 10 01 20 00 21 10 01 02 01 11 10 01 20 12 02 10 10 02 00 10 01 02 00 11 00 11 10 01 11 12 12 20 01 11 00 12 01 10 12 10 02 00 01 02 22 21 20 10 02 00 12 00 00 20 10 01 collection point 3; 2 da ys fe c e s collection start collection point 3 end collection point 3 bod yw eight (g) fo o d on cage (g) bodyw eight (g) food o ff c a g e (g) 32.9 33.2 30.1 78.3 30.2 68.3 30 30.2 28.3 73.4 28.4 63.2 29.2 31.1 30.4 67.0 29.6 56.6 26.3 38.3 26.5 33.4 30 30.8 30.5 27 94.8 30.7 27.1 81.0 32.2 30 32.8 30.0 31.2 97.1 31.8 80.4 33.6 30.1 42.0 33.1 30.3 36.8 30 30.9 32.5 26.3 85.6 32.7 25.9 67.2 26.9 29 60.9 46.3 26.5 29.1 52.8 41.2 28.4 39.9 29.1 34.3 29.2 40.9 29.2 35.5 32.3 29.2 56.5 32.5 29.3 43.8 26.1 46.1 26.4 41.0 28.8 29.8 29.1 30.2 25.1 1 1 4 .5 25.4 1 0 0 .9 29.4 27.6 34.9 37.9 29.6 27.8 29.9 33.3 29.6 29.9 28.7 29.6 61.5 29.2 29.8 50.2 30.5 30.5 30.7 26.2 1 3 0 .6 31.1 26.5 1 1 1 .9 26.9 28.0 30.1 27.2 70.0 30.9 27.5 58.0 27.7 67.9 27.5 57.3 29.1 25.5 29.8 25.6 28.6 29.2 28.8 30.1 1 3 8 .4 52.3 29.1 29.6 1 1 9 .7 47.7 28.6 37.3 28.6 31.9 30.1 29.7 74.9 30.6 30.2 52.3 27 28.4 39.9 35.4 27.3 28.6 35.1 30.3 28.7 44.3 28.7 38.8 31.4 32.1 27 66.8 27.4 55.8 29.7 30.2 28 60.0 28.5 49.9 25.3 25.6 26.9 27.2 28.8 28.6 30.9 26.3 1 4 2 .0 46.7 30.6 26.6 1 2 4 .9 41.8 29.1 35.7 28.5 30.7 27.8 42.4 27.8 37.5 26.8 46.1 27.0 40.3 28.9 28.7 27.6 90.6 28.2 81.1 26.2 39.7 27.1 34.2 26.7 26.7 27.2 76.5 27.3 66.5 23.6 23.8 25.7 65.9 25.4 56.1 A v e ra g e bodyw eight (g) 3 3 .0 5 3 0 .1 5 3 0 .1 0 2 8 .3 5 3 0 .1 5 3 0 .0 0 2 6 .4 0 3 0 .4 0 3 0 .6 0 2 7 .0 5 3 2 .5 0 3 0 .0 0 3 1 .5 0 3 3 .3 5 3 0 .2 0 3 0 .4 5 3 2 .6 0 2 6 .1 0 2 6 .7 0 2 9 .0 5 2 8 .7 5 2 9 .2 0 3 2 .4 0 2 9 .2 5 2 6 .2 5 2 8 .9 5 3 0 .0 0 2 5 .2 5 2 9 .5 0 2 7 .7 0 2 9 .7 5 2 8 .9 5 2 9 .7 0 3 0 .5 0 3 0 .9 0 2 6 .3 5 2 7 .4 5 3 0 .5 0 2 7 .3 5 2 7 .6 0 2 9 .4 5 2 5 .5 5 2 8 .9 0 2 8 .9 5 2 9 .8 5 2 8 .6 0 3 0 .3 5 2 9 .9 5 2 7 .1 5 2 8 .5 0 2 8 .7 0 3 1 .7 5 2 7 .2 0 2 9 .9 5 2 8 .2 5 2 5 .4 5 2 7 .0 5 2 8 .7 0 3 0 .7 5 2 6 .4 5 2 8 .8 0 2 7 .8 0 2 6 .9 0 2 8 .8 0 2 7 .9 0 2 6 .6 5 2 6 .7 0 2 7 .2 5 2 3 .7 0 2 5 .5 5 Food in take (g) coll. po in t 3 10.0 10.2 10.4 4.9 13.8 16.7 5.2 18.4 8.1 5.1 5.6 5.4 12.7 5.1 13.6 5.0 4.6 11.3 18.7 12.0 10.6 18.7 4.6 5.4 2 2 .6 4.8 5.1 5.5 11.0 10.1 17.1 4.9 5.0 4.9 5.8 9.5 5.5 10.0 9.8 Page A55 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Fecal weight Group 1 1 1 1 1 2 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 5 5 5 5 5 5 6 6 6 6 6 7 7 7 7 7 7 7 cage# 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 Feces collection point 1; 2 days collection number of Tube empty Tube full T ube full after freeze drying mice (g) (g) (g) 2 6.6630 8.3248 8.0444 2 6.6490 8.6605 8.3426 2 6.6221 8.6309 8.3229 1 6.6808 7.664 7.4697 3 6.6712 9.4474 8.9658 3 6.6634 9.8825 9.4253 1 6.6794 7.8244 7.6266 3 6.6207 10.2937 9.7316 2 6.6605 8.2584 1 6.6630 7.5596 8.0008 7.4162 1 6.6697 7.5244 7.3942 1 6.6594 7.5056 7.3806 2 6.6379 9.0681 8.6519 1 6.6624 7.5339 7.4049 3 6.6568 9.433 8.9562 1 6.6607 7.5433 7.3604 1 6.6312 7.6683 7.5344 2 6.6765 8.6953 8.3655 4 6.6311 10.3697 9.7743 2 6.6493 8.6134 8.2667 2 6.6603 8.6425 8.2974 4 6.6918 10.4134 9.8868 1 6.6683 7.7517 1 6.7028 7.6752 7.5567 7.5296 2 6.6868 9.2271 1 6.6825 7.5842 8.8008 7.456 1 6.6889 7.8388 7.6669 1 6.6648 7.6251 2 6.6617 8.6518 7.4945 8.3356 2 6.6503 8.6434 8.3383 4 6.6110 9.8507 9.3193 1 6.6541 7.4635 7.3215 1 6.6615 7.3485 7.2406 1 6.6589 7.5622 7.3939 1 6.6820 7.476 7.3376 2 6.6335 8.4094 1 6.6727 7.4706 8.0542 7.3318 2 6.6890 8.3375 2 6.6706 8.2396 8.054 7.9761 freeze dried feces (g) 1.3814 1.6936 1.7008 0.7889 2.2946 2.7619 0.9472 3.1109 1.3403 0.7532 0.7245 0.7212 2.0140 0.7425 2.2994 0.6997 0.9032 1.6890 3.1432 1.6174 1.6371 3.1950 0.8884 0.8268 2.1140 0.7735 0.9780 0.8297 1.6739 1.6880 2.7083 0.6674 0.5791 0.7350 0.6556 1.4207 0.6591 1.3650 1.3055 Page A56 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Group 1 1 1 1 1 2 2 2 2 2 3 3 3 3 3 3 3 4 4 4 4 5 5 5 5 5 5 6 6 6 6 6 7 7 7 7 7 7 7 cage# 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 Feces collection point 2; 3 days collection number of Tube empty Tube full T ube full after freeze drying mice 2 (g) 6.6728 (g) 9.043 (g) 8.654 2 6.6313 9.7853 9.3421 2 6.6987 9.5813 9.188 1 6.6499 8.1391 3 6.6805 10.6433 7.9395 10.0911 3 6.6610 11.3687 10.736 1 6.6450 8.426 8.1553 3 6.6479 12.3927 11.5086 2 6.6676 9.2172 8.8482 1 6.6137 8.0501 7.8405 1 6.6564 8.1514 7.945 1 6.6806 8.3368 8.1005 2 6.6554 10.2976 9.7616 1 6.6905 8.1358 7.9299 3 6.6709 11.0804 10.4427 1 6.6500 8.0103 7.7806 1 6.6622 8.2678 8.0649 2 6.6790 9.8571 9.3923 4 6.6452 12.0852 11.2859 2 6.6370 9.933 2 6.6464 9.514 9.4414 9.0495 4 6.6068 12.3762 11.578 1 6.6411 8.2187 7.9954 1 6.6557 8.1263 7.9237 2 6.6822 10.3758 9.8975 1 6.6134 8.0183 7.792 1 6.6799 8.1596 7.914 1 6.6762 8.1471 7.9636 2 6.6989 9.824 9.3799 2 6.6732 9.5294 9.1304 4 6.6621 11.3048 1 6.6310 7.9252 10.6299 7.7404 1 6.6902 8.1846 7.96 1 6.6712 7.9152 7.7309 1 6.6337 7.9533 7.7519 2 6.6633 9.2718 8.8526 1 6.6324 7.8893 7.7077 2 6.6776 9.1802 8.8063 2 6.6697 9.253 8.8469 freeze dried feces (g) 1.9812 2.7108 2.4893 1.2896 3.4106 4.0750 1.5103 4.8607 2.1806 1.2268 1.2886 1.4199 3.1062 1.2394 3.7718 1.1306 1.4027 2.7133 4.6407 2.8044 2.4031 4.9712 1.3543 1.2680 3.2153 1.1786 1.2341 1.2874 2.6810 2.4572 3.9678 1.1094 1.2698 1.0597 1.1182 2.1893 1.0753 2.1287 2.1772 Page A57 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Feces collection point 3; 2 days collection Group cage# number of Tube empty Tube full Tube full after freeze drying freeze dried 1 1 mice 2 6.6(g4)29 8.5(g8)21 8.2(g3)99 feces (g) 1.5970 1 2 2 6.6725 8.9822 8.6509 1.9784 1 3 2 6.6831 8.9939 8.653 1.9699 1 4 1 6.6645 7.7309 7.5727 0.9082 1 5 3 6.6432 9.9317 9.4021 2.7589 2 6 3 6.6844 10.106 9.6123 2.9279 2 7 1 6.6652 7.8515 7.6749 1.0097 2 8 3 6.6453 10.6479 10.0341 3.3888 2 9 2 6.6397 8.3585 8.1165 1.4768 2 10 1 6.6569 7.7971 7.6376 0.9807 3 11 1 6.6860 7.7179 7.5628 0.8768 3 12 1 6.6590 7.7398 7.58 0.9210 3 13 2 6.6605 9.3189 8.8877 2.2272 3 14 1 6.6334 7.6444 7.4947 0.8613 3 15 3 6.6582 9.6295 9.1847 2.5265 33 1167 11 66..66164952 77..67385914 77..4683119 00..89667148 4 18 2 6.6935 9.0966 8.7345 2.0410 4 19 4 6.6306 10.6276 10.077 3.4464 4 20 2 6.6585 9.1542 8.7793 2.1208 4 21 2 6.6901 8.8739 8.5242 1.8341 5 22 4 6.6840 10.9177 10.2953 3.6113 5 23 1 6.6687 7.6866 7.5361 0.8674 5 24 1 6.6635 7.8102 7.6563 0.9928 5 25 2 6.6833 9.43 9.0427 2.3594 5 26 1 6.6333 7.6942 7.5479 0.9146 5 27 1 6.6752 7.7479 7.5966 0.9214 6 28 1 6.6351 7.7734 7.6365 1.0014 6 29 2 6.6633 9.0885 8.5695 1.9062 6 30 2 6.6611 8.8705 8.5556 1.8945 6 31 4 6.6657 10.3688 9.9106 3.2449 6 32 1 6.6786 7.7434 7.5484 0.8698 7 33 1 6.6860 7.6314 7.485 0.7990 7 34 1 6.6887 7.5625 7.393 0.7043 7 35 1 6.6783 7.9028 7.6867 1.0084 7 36 2 6.6551 8.561 8.2858 1.6307 7 37 1 6.6481 7.617 7.4543 0.8062 7 38 2 6.6522 8.6462 8.3568 1.7046 7 39 2 6.6641 8.7084 8.3702 1.7061 Page A58 of A172 Appendix to TNO-report of 3M-02 Final version Feces weight, bodyweight and food intake GC samples GC-1 Fecescollection3M-02week6; collectionpoint 1,2dayscollection Group cage# fecescollected Bodyweight Foodintake code (g) (g) (g) 1:1-1 1 1,2 3.075 123.6 23.2 1:1-2 1 3,4 2.4897 87.25 18 1:1-3 1 5 2.2946 88.55 16.8 1:2-4 2 6 2.7619 94.55 19.9 1:2-5 2 7,8 4.0581 126.6 27.7 1:2-6 2 9,10 2.0935 82.2 16.3 1:3-7 3 11,12,13 3.4597 118 26.2 1:3-8 3 15 2.2994 83.55 16.5 1:3-9 3 14,16,17 2.3454 82.8 18.3 1:4-10 4 18 1.689 59.5 12 1:4-11 1:4-12 t 44 19 3.1432 20,21 3.2545 116.4 112.2 21.7 24 1:5-13 5 22 3.195 110.7 21.5 1:5-14 5 24,25 2.9408 88.35 19.6 1:5-15 5 23,26,27 2.6399 84.6 19.5 1:6-16 6 28,29 2.5036 87.1 17.6 1:6-17 6 31 2.7083 112.8 20.3 1:6-18 6 30,32 2.3554 85.4 17.2 1:7-19 7 33,34,35 1.9697 81.35 16.8 1:7-20 7 36,37 2.0798 82.25 16.9 1:7-21 7 38,39 2.6705 101.05 21.9 GC-2 code 2:1-1 2:1-2 2:1-3 2:2-4 2:2-5 2:2-6 2:3-7 2:3-8 2:3-9 2:4-10 2:4-11 2:4-12 2:5-13 2:5-14 2:5-15 2:6-16 2:6-17 2:6-18 2:7-19 2:7-20 2:7-21 Fecescollection3M-02week6; collectionpoint2, 3dayscollection | Group cage# fecescollected Bodyweight Foodintake (g) (g) (g) 1 1,2 4.692 122.45 36.8 1 3,4 3.7789 86.55 28.8 1 5 3.4106 88.2 25.6 2 6 4.075 94.25 28.8 2 7,8 6.371 126.45 45.4 2 9,10 3.4074 82.1 28.2 3 11,12,13 5.8147 118.75 44.7 3 15 3.7718 83.5 28.3 3 14,16,17 3.7727 83.05 29.3 4 18 2.7133 58.85 19.8 44 19 20,21 4.6407 5.2075 116.55 111.85 35.2 38.2 5 22 4.9712 111.6 36.5 5 24,25 4.4833 88.5 32.2 5 23,26,27 3.767 85.55 30.3 6 28,29 3.9684 87.15 29.7 6 31 3.9678 112.45 31 6 30,32 3.5666 84.55 27.9 7 33,34,35 3.4477 82.35 29.2 7 36,37 3.2646 82.75 26.5 7 38,39 4.3059 101.95 35 GC-3 code 3:1-1 3:1-2 3:1-3 3:2-4 3:2-5 3:2-6 3:3-7 3:3-8 3:3-9 3:4-10 3:4-11 3:4-12 3:5-13 3:5-14 3:5-15 3:6-16 3:6-17 3:6-18 3:7-19 3:7-20 3:7-21 Fecescollection3M-02week6; collectionpoint3, 2dayscollection Group cage# fecescollected Bodyweight Foodintake (g) (g) 1 1,2 3.5754 121.65 (g) 20.2 1 3,4 2.8781 86.55 15.3 1 5 2.7589 88.05 13.8 2 6 2.9279 94 16.7 2 7,8 4.3985 126.6 23.6 2 9,10 2.4575 81.85 13.2 3 11,12,13 4.025 119.6 23.7 3 15 2.5265 84.2 13.6 3 14,16,17 2.6905 83.45 14.7 4 18 2.041 58.7 11.3 4 19 3.4464 117.45 18.7 4 20,21 3.9549 112.9 22.6 5 22 3.6113 112.85 18.7 5 24,25 3.3522 88.9 28 5 23,26,27 2.7034 85.5 14.5 6 28,29 2.9076 87.65 16.5 6 31 3.2449 111.95 17.1 6 30,32 2.7643 84.65 15 7 33,34,35 2.5117 83.5 15.7 7 36,37 2.4369 83.35 15 7 38,39 3.4107 103.2 19.8 04-12-2006 Page A59 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 E2. Fecal bile acid measurements 1:1-1____________________________ weight feces 5.8 mg a-muricholate deoxycholate cholate lithocholate U-muricholate w-muricholate hyodeo/urso area 770 2880 837 1412 3635 3854 411 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 1062.6 2880 979 1412 3925.8 5704 411 % |jg bile acid ng bile acid nmol bile acid/ mg feces mg feces 6.5 0.447 77.1 17.6 1.211 208.9 0.189 0.532 6.0 0.412 71.0 0.174 8.6 0.594 102.4 0.272 24.0 1.651 284.7 0.697 34.8 2.399 413.6 2.5 0.173 29.8 1.012 0.076 total I 13799 I | 16375 | 100 | 7 | 1187 | 3.0~ nor-hyodeoxy | 23775 | 1 | 23775 | 23775 1:1-2____________________________ weight feces 6 mg a-muricholate deoxycholate cholate lithocholate U-muricholate w-muricholate hyodeo/urso area 481 1551 1143 2203 2222 5717 261 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 663.78 1551 1337 2203 2399.76 8461 261 % jg bile acid ng bile acid nmol bile acid/ mg feces mg feces 3.9 0.276 46.0 0.113 9.2 0.645 107.4 0.274 7.9 0.556 92.6 13.1 0.916 152.6 0.227 0.405 14.2 0.997 166.2 0.407 50.1 3.517 586.1 1.5 0.108 18.1 1.435 0.046 total I 13578 I | 16877 | 100 | 7 | 1169 | 2.9~ nor-hyodeoxy I 24059 | 1 | 24059 | 24059 1:1-3____________________________ weight feces 5.5 mg a-muricholate deoxycholate cholate lithocholate U-muricholate w-muricholate hyodeo/urso area 304 1047 535 1334 1317 3031 192 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 419.52 1047 626 1334 1422.36 4486 192 % jg bile acid ng bile acid nmol bile acid/ mg feces mg feces 4.4 0.269 48.9 0.120 11.0 0.672 122.1 6.6 0.401 73.0 14.0 0.856 155.6 0.311 0.179 0.413 14.9 0.912 165.9 0.406 47.1 2.877 523.1 2.0 0.123 22.4 1.280 0.057 total I 7760 I I 9527 | 100 | 6 | 1111 | 2.8~ nor-hyodeoxy | 15591 | 1 | 15591 | 15591 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 Page A60 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 2: 1-1___________________________ weight feces 7.2 mg area response area corrected % |jg bile acid ig bile acid nmol bile acid/ factor for response factor mg feces mg feces a-muricholate 314 1.38 433.32 13.0 0.940 130.5 0.319 deoxycholate 688 1 688 20.7 1.492 207.2 0.528 cholate 213 1 249 7.5 0.540 75.0 0.184 lithocholate 335 1 335 10.1 0.726 100.9 0.268 B-muricholate 803 1.08 867.24 26.1 1.880 261.2 0.639 w-muricholate hyodeo/urso 507 1 1 750 22.6 1.627 226.0 0.553 0 0.0 0.000 0.0 0.000 total | 2860 | | 3323 | 100 | 7 | 1001 | 2.5 nor-hyodeoxy | 4612 | 1 | I 2:1-2 weight feces 7.2 mg 4612 | 4612 a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 1014 2554 2363 2730 4506 9183 213 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 1399.32 2554 2765 2730 4866.48 13591 213 % jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 5.0 0.472 65.5 0.160 9.1 0.861 119.6 0.305 9.8 0.932 129.4 0.317 9.7 0.920 127.8 0.339 17.3 1.640 227.8 48.3 4.581 636.3 0.558 1.557 0.8 0.072 10.0 0.025 total | 22563 | | 28118 | 100 | 9 | 1316 | 3.3 nor-hyodeoxy | 29667 | 1 | 29667 | 29667 | 2:1-3 weight feces 5.1 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 1430 3201 3202 808 5434 7559 255 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 1973.4 3201 3746 808 5868.72 11187 255 % jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 7.3 0.452 88.6 11.8 0.733 143.6 13.9 0.857 168.1 3.0 0.185 36.3 21.7 1.343 263.3 41.4 2.560 502.0 0.9 0.058 11.4 0.217 0.366 0.411 0.096 0.645 1.229 0.029 total I 21889 | | 27040 | 100 | 6 | 1213 | 3.0 nor-hyodeoxy | 43696 | 1 | 43696 | 43696 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 Page A61 of A172 Appendix to TNO-report of 3M-02 Final version | 3:1-1 weight feces 7 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 755 6854 1031 1211 6883 6151 349 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 1041.9 6854 1206 1211 7433.64 9103 349 % 3.8 25.2 4.4 4.5 27.3 33.5 1.3 |jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 0.319 45.6 0.112 2.101 300.1 0.764 0.370 52.8 0.129 0.371 53.0 0.141 2.278 325.5 0.797 2.790 0.107 398.6 15.3 0.976 0.039 total | 23234 | | 27199 | 100 | 8 | 1191 | 3. nor-hyodeoxy | 32626 | 1 | 32626 | 32626 | 3:1-2 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 6.6 area 475 1558 748 1489 1894 3897 198 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 655.5 1558 875 1489 2045.52 5768 198 % 5.2 12.4 7.0 11.8 16.2 45.8 1.6 |jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 0.325 0.771 0.433 0.737 1.013 2.856 0.098 49.2 116.9 65.7 111.7 153.5 432.7 14.9 0.120 0.298 0.161 0.297 0.376 1.059 0.038 total | 10259 | | 12589 | 100 | 6 | 944 | 2~ nor-hyodeoxy | 20195 | 1 | 20195 | 20195 | 3:1-3 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 6.1 area 750 1906 1166 974 3492 4213 396 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 1035 1906 1364 974 3771.36 6235 396 % 6.6 12.2 8.7 6.2 24.0 39.8 2.5 |jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 0.429 0.791 0.566 0.404 1.565 2.587 0.164 70.4 129.6 92.8 66.2 256.5 424.1 26.9 0.172 0.330 0.227 0.176 0.628 1.038 0.069 total | 12897 | | 15682 | 100 | 7 | 1067 | 2.6 nor-hyodeoxy | 24103 | 1 | 24103 | 24103 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 04-12-2006 Page A62 of A172 Appendix to TNO-report of 3M-02 Final version 1:2-4 weight feces 6.3 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 133 741 488 509 758 1756 133 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 183.54 741 571 509 818.64 2599 133 % 3.3 13.3 10.3 9.2 14.7 46.8 2.4 |jg bile acid ng bile acid nmol bile acid/ mg feces mg feces 0.211 0.853 33.5 135.4 0.082 0.345 0.657 104.3 0.255 0.586 93.0 0.247 0.942 2.991 0.153 149.6 474.8 24.3 0.366 1.162 0.062 total I 4518 I I 5555 | 100 | 6 | 1015 | 25 nor-hyodeoxy 8688 1:2-5 weight feces 6.4 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 385 1785 1437 1980 5071 4256 151 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 531.3 1785 1681 1980 5476.68 6299 151 % 3.0 10.0 9.4 11.1 30.6 35.2 0.8 |jg bile acid ng bile acid nmol bile acid/ mg feces mg feces 0.208 0.699 0.659 0.776 2.146 2.468 0.059 32.5 109.3 102.9 121.2 335.3 385.6 9.2 0.080 0.278 0.252 0.322 0.821 0.944 0.024 total I 15065 I I 17904 | 100 | 7 | 1096 | 2T nor-hyodeoxy | 25522 | 1 | 25522 | 25522 1:2-6 weight feces 5.3 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 696 3055 1508 3344 2771 7511 363 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 960.48 3055 1764 3344 2992.68 11116 363 % 4.1 12.9 7.5 14.2 12.7 47.1 1.5 |jg bile acid ng bile acid nmol bile acid/ mg feces mg feces 0.324 1.032 0.596 1.130 1.011 3.756 0.123 61.2 194.7 112.5 213.2 190.8 708.6 23.1 0.150 0.496 0.275 0.566 0.467 1.734 0.059 total I 19248 I | 23596 | 100 | 8 | 1504 | 3T nor-hyodeoxy | 29599 | 1 | 29599 | 29599 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 04-12-2006 Page A63 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 2:2-4 weight feces 7.7 mg a-muricholate deoxycholate cholate lithocholate U-muricholate w-muricholate hyodeo/urso area 564 1799 924 1298 1925 3892 response area corrected factor for response factor % |jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 1.38 778.32 6.1 0.518 67.3 0.165 1 1799 14.1 1.198 155.6 0.396 1 1081 8.4 0.720 93.5 0.229 1 1298 10.1 0.864 112.2 0.298 1.08 2079 16.2 1.384 179.8 0.440 1 5760 45.0 3.836 498.1 1.219 1 0 0.0 0.000 0.0 0.000 total | 10402 | | 12796 | 100 | 9 | 1107 | 2.7 nor-hyodeoxy | 15018 | 1 | 15018 | 15018 2:2-5 weight feces 6.6 mg a-muricholate deoxycholate cholate lithocholate U-muricholate w-muricholate hyodeo/urso area 521 1246 771 1507 3321 3749 322 response area corrected % jg bile acid ig bile acid nmol bile acid/ factor for response factor mg feces mg feces 1.38 718.98 5.2 0.391 59.2 0.145 1 1246 9.0 0.677 102.6 0.261 1 902 6.5 0.490 74.3 0.182 1 1507 10.9 0.819 124.1 0.330 1.08 3586.68 25.9 1.949 295.3 0.723 1 5549 40.1 3.016 456.9 1.118 1 322 2.3 0.175 26.5 0.068 total I 11437 I I 13831 | 100 | 8 | 1139 | 2.8 nor-hyodeoxy | 18400 | 1 | 18400 | 18400 2:2-6 weight feces 6.4 mg a-muricholate deoxycholate cholate lithocholate U-muricholate w-muricholate hyodeo/urso area 1341 4170 1935 3343 3407 9002 474 response area corrected factor for response factor % jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 1.38 1850.58 6.4 0.624 97.4 0.238 1 4170 14.3 1.405 219.6 0.559 1 2264 7.8 0.763 119.2 0.292 1 3343 11.5 1.127 176.0 0.467 1.08 3679.56 12.6 1.240 193.7 0.474 1 13323 45.8 4.490 701.5 1.717 1 474 1.6 0.160 25.0 0.064 total I 23672 I | 29104 | 100 | 10 | 1532 | 3.8 nor-hyodeoxy | 29674 | 1 | 29674 | 29674 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 Page A64 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 3:2-4 weight feces a -m uricholate deoxycholate cholate lithocholate U-muricholate w-muricholate hyodeo/urso 6.4 area 469 1577 949 839 2511 4030 280 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 647.22 1577 1110 839 2711.88 5964 280 % 4.9 12.0 8.5 6.4 20.7 45.4 2.1 |jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 0.389 0.947 60.7 148.0 0.149 0.377 0.667 104.2 0.255 0.504 78.7 0.209 1.629 3.583 0.168 254.5 559.8 26.3 0.623 1.370 0.067 total I 10655 I I 13130 | 100 | 8 | 1232 | 3.0 nor-hyodeoxy | 16647 | 1| 16647 | 16647 3:2-5 weight feces a-m uricholate deoxycholate cholate lithocholate U-muricholate w-muricholate hyodeo/urso 6.5 area 438 1197 858 906 3408 2988 364 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 604.44 1197 1004 906 3680.64 4422 364 % 5.0 9.8 8.2 7.4 30.2 36.3 3.0 jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 0.321 0.635 49.3 97.7 0.121 0.249 0.532 0.481 1.952 2.345 0.193 81.9 73.9 300.3 360.8 29.7 0.200 0.196 0.735 0.883 0.076 total I 10159 I I 12178 | 100 | 6 | 994 | 2.5 nor-hyodeoxy I 18855 | 1| 18855 | 18855 3:2-6 weight feces 5.5 mg a-m uricholate deoxycholate cholate lithocholate U-muricholate w-muricholate hyodeo/urso area 871 2878 1791 1999 2933 6248 527 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 1201.98 2878 2095 1999 3167.64 9247 527 % 5.7 13.6 9.9 9.5 15.0 43.8 2.5 jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 0.458 83.4 0.204 1.098 199.6 0.508 0.799 145.3 0.356 0.762 138.6 0.368 1.208 219.7 0.538 3.527 0.201 641.2 36.5 1.569 0.093 total I 17247 I | 21116 | 100 | 8 | 1464 | 3.6 nor-hyodeoxy | 26219 | 1| 26219 | 26219 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 Page A65 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 1:3-7___________________________ weight feces 5.8 mg a-m u rich olate deoxycholate cholate lithocholate U-muricholate w -m u rich o la te hyodeo/urso area 463 2160 560 2503 3081 5475 269 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 638.94 2160 655 2503 3327.48 8103 269 % 3.6 12.2 3.7 14.2 18.8 45.9 1.5 |jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 0.283 0.956 48.7 164.8 0.119 0.420 0.290 50.0 0.122 1.108 191.0 0.507 1.472 3.586 0.119 253.9 618.2 20.5 0.621 1.513 0.052 total | 14511 | I 17657 | 100 | 8 | 1347 | 3~ nor-hyodeoxy | 22598 | 1| 22598 | 22598 1:3-8___________________________ weight feces 5.4 mg a-m u rich olate deoxycholate cholate lithocholate U-muricholate w -m u rich o la te hyodeo/urso area 258 1480 573 1667 1531 3397 212 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 356.04 1480 670 1667 1653.48 5028 212 % 3.2 13.4 6.1 15.1 14.9 45.4 1.9 jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 0.226 0.939 0.425 1.058 1.049 3.190 0.135 41.8 173.9 78.8 195.9 194.3 590.8 24.9 0.102 0.443 0.193 0.520 0.476 1.446 0.063 total | 9118 | I 11066 | 100 | 7 | 1300 | 3~ nor-hyodeoxy I 15759 | 1| 15759 | 15759 1:3-9___________________________ weight feces 6.4 mg a-m u rich olate deoxycholate cholate lithocholate U-muricholate w -m u rich o la te hyodeo/urso area 483 1604 840 2300 2706 3466 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 666.54 1604 983 2300 2922.48 5130 0 % 4.9 11.8 7.2 16.9 21.5 37.7 0.0 jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 0.414 64.7 0.158 0.997 0.611 155.8 95.5 0.397 0.234 1.430 1.817 3.189 0.000 223.4 283.8 498.2 0.0 0.593 0.695 1.219 0.000 total | 11399 | I 13606 | 100 | 8 | 1321 | 3~ nor-hyodeoxy | 16088 | 1| 16088 | 16088 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 Page A66 of A172 Appendix to TNO-report of 3M-02 Final version 2:3-7 weight feces 5 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 213 1811 1070 2080 2392 4005 367 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 293.94 1811 1252 2080 2583.36 5927 367 % 2.1 12.7 8.7 14.5 18.0 41.4 2.6 |jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 0.139 0.858 27.9 171.6 0.068 0.437 0.593 118.7 0.290 0.986 197.1 0.523 1.224 2.809 0.174 244.8 561.8 34.8 0.599 1.375 0.089 total I 11938 I I 14315 | 100 | 7 | 1357 | ~ nor-hyodeoxy | 21102 | 1 | 21102 | 21102 2:3-8______________________ weight feces 7.3 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 222 790 602 1050 1101 2234 135 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 306.36 790 704 1050 1189.08 3306 135 % 4.1 10.6 9.4 14.0 15.9 44.2 1.8 jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 0.300 41.0 0.100 0.772 0.689 105.8 94.3 0.269 0.231 1.026 140.6 0.373 1.162 159.2 0.390 3.232 0.132 442.8 18.1 1.084 0.046 total I 6134 I I 7481 | 100 | 7 | 1002 | ~ nor-hyodeoxy | 10229 | 1 | 10229 | 10229 2:3-9______________________ weight feces 5.3 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 887 2496 1947 482 4734 4874 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 1224.06 2496 2278 482 5112.72 7214 0 % 6.5 13.3 12.1 2.6 27.2 38.4 0.0 jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 0.333 0.679 0.620 0.131 1.391 1.963 0.000 62.9 128.2 117.0 24.8 262.5 370.4 0.0 0.154 0.326 0.286 0.066 0.643 0.907 0.000 total I 15420 I I 18806 | 100 | 5 | 966 | ~ nor-hyodeoxy | 36744 | 1 | 36744 | 36744 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 04-12-2006 Page A67 of A172 Appendix to TNO-report of 3M-02 Final version 3:3-7______________________ weight feces 8.2 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 727 3031 1265 1974 4421 5331 401 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 1003.26 3031 1480 1974 4774.68 7890 401 % 4.9 14.7 7.2 9.6 23.2 38.4 2.0 |jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 0.379 1.146 46.3 139.8 0.113 0.356 0.560 0.747 68.3 91.0 0.167 0.242 1.806 2.984 0.152 220.2 363.9 18.5 0.539 0.891 0.047 total I 17150 1 I 20554 | 100 | 8 | 948 | ~ nor-hyodeoxy | 26440 | 1 | 26440 | 26440 3:3-8______________________ weight feces 6.4 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 541 1842 998 1904 2601 4796 270 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 746.58 1842 1168 1904 2809.08 7098 270 % 4.7 11.6 7.4 12.0 17.7 44.8 1.7 jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 0.264 41.3 0.101 0.652 0.413 0.674 101.8 64.5 105.2 0.259 0.158 0.279 0.994 155.3 0.380 2.511 0.096 392.3 14.9 0.960 0.038 total | 12952 | | 15837 | 100 | 6 | 875 | ~ nor-hyodeoxy | 28268 | 1 | 28268 | 28268 3:3-9______________________ weight feces 7 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 612 2141 1127 2027 3995 4490 224 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 844.56 2141 1319 2027 4314.6 6645 224 % 4.8 12.2 7.5 11.6 24.6 37.9 1.3 jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 0.381 54.5 0.133 0.967 138.1 0.352 0.595 0.915 85.0 130.7 0.208 0.347 1.948 3.000 0.101 278.3 428.6 14.4 0.681 1.049 0.037 total | 14616 1 | 17515 | 100 | 8 | 1130 | ~ nor-hyodeoxy | 22149 | 1 | 22149 | 22149 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 04-12-2006 Page A68 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 1:4-10 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 5.1 area 103 354 286 394 349 1185 235 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 142.14 354 335 394 376.92 1754 235 % 4.0 9.9 9.3 11.0 10.5 48.8 6.5 |jg bile acid 0.114 0.283 0.268 0.315 0.302 1.404 0.188 ng bile acid/ mg feces 22.3 55.6 52.5 61.8 59.2 275.2 36.9 nmol bile acid/ mg feces 0.055 0.142 0.129 0.164 0.145 0.674 0.094 total I 2906 I I 3590 | 100 | 3 | 563 | ~ T nor-hyodeoxy | 12494 | 1 | 12494 | 12494 1:4-11 weight feces 4.8 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 276 396 184 214 555 896 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 380.88 396 215 214 599.4 1326 0 % 12.2 12.6 6.9 6.8 19.1 42.3 0.0 |jg bile acid 0.454 0.472 0.257 0.255 0.715 1.581 0.000 ng bile acid/ mg feces 94.6 98.3 53.5 53.1 148.9 329.3 0.0 nmol bile acid/ mg feces 0.231 0.250 0.131 0.141 0.364 0.806 0.000 total I 2521 I I 3132 | 100 | 4 | 778 | T nor-hyodeoxy 8389 1:4-12 weight feces 6 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso total I area 320 852 475 954 954 2059 5614 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 441.6 852 556 954 1030.32 3047 0 | I 6881 | % 6.4 12.4 8.1 13.9 15.0 44.3 0.0 100 |jg bile acid ng bile acid/ nmol bile acid/ mg feces mg feces 0.390 0.753 0.491 0.843 0.911 2.694 0.000 65.1 125.5 81.9 140.6 151.8 449.0 0.0 0.159 0.320 0.200 0.373 0.372 1.099 0.000 1 .5| 6 | 1014 | nor-hyodeoxy | 11311 | 1 | 11311 | 11311 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 Page A69 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 2:4-10 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 6.2 area 361 1051 1247 1420 979 2197 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 498.18 1051 1459 1420 1057.32 3252 0 % 5.7 12.0 16.7 16.3 12.1 37.2 0.0 |jg bile acid 0.258 0.544 0.755 0.735 0.547 1.682 0.000 ng bile acid/ mg feces 41.6 87.7 121.7 118.5 88.2 271.3 0.0 nmol bile acid/ mg feces 0.102 0.223 0.298 0.315 0.216 0.664 0.000 total I 7255 I | 8737 | 100 | 5 | 729 | ~ T ^ nor-hyodeoxy | 19330 | 1 | 19330 | 19330 2:4-11 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 6.6 area 842 1126 866 1217 2527 3746 481 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 1161.96 1126 1013 1217 2729.16 5544 481 % 8.8 8.5 7.6 9.2 20.6 41.8 3.6 |jg bile acid 0.510 0.494 0.444 0.534 1.197 2.432 0.211 ng bile acid/ mg feces 77.2 74.8 67.3 80.9 181.4 368.4 32.0 nmol bile acid/ mg feces 0.189 0.191 0.165 0.215 0.444 0.902 0.081 total I 10805 | | 13272 | 100 | 6 | 882 | T ? nor-hyodeoxy | 22800 | 1 | 22800 | 22800 2:4-12 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 7.6 area 543 902 1180 1019 1622 2624 206 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 749.34 902 1381 1019 1751.76 3884 206 % 7.6 9.1 14.0 10.3 17.7 39.3 2.1 |jg bile acid 0.555 0.668 1.023 0.755 1.297 2.876 0.153 ng bile acid/ mg feces 73.0 87.9 134.5 99.3 170.7 378.5 20.1 nmol bile acid/ mg feces 0.179 0.224 0.329 0.264 0.418 0.926 0.051 total I 8096 | | 9892 | 100 | 7 | 964 | H * nor-hyodeoxy | 13502 | 1 | 13502 | 13502 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 Page A70 of A172 Appendix to TNO-report of 3M-02 Final version 3:4-10 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 8.1 area 374 928 737 749 1189 2355 244 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 516.12 928 862 749 1284.12 3485 244 % 6.4 11.5 10.7 9.3 15.9 43.2 3.0 |jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 0.307 38.0 0.093 0.553 68.2 0.174 0.514 63.4 0.155 0.446 55.1 0.146 0.765 2.076 0.145 94.4 256.3 17.9 0.231 0.627 0.046 total I 6576 I | 8069 | 100 | 5 | 593 | 1~ nor-hyodeoxy | 16790 | 1 | 16790 | 16790 3:4-11 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 8.3 area 474 1184 335 668 2030 2413 257 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 654.12 1184 392 668 2192.4 3571 257 % 7.3 13.3 4.4 7.5 24.6 40.0 2.9 |jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 0.475 0.860 0.285 0.485 1.592 2.593 0.187 57.2 103.6 34.3 58.4 191.8 312.5 22.5 0.140 0.264 0.084 0.155 0.469 0.765 0.057 total I 7361 | I 8919 | 100 | 6 | 780 | 1~ nor-hyodeoxy | 13770 | 1 | 13770 | 13770 3:4-12 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 6.6 area 436 831 1182 693 1774 2161 172 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 601.68 831 1383 693 1915.92 3198 172 % 6.8 9.4 15.7 7.9 21.8 36.4 2.0 |jg bile acid ig bile acid nmol bile acid/ mg feces mg feces 0.394 0.544 59.7 82.4 0.146 0.210 0.905 0.454 1.254 137.1 68.7 190.0 0.336 0.182 0.465 2.093 0.113 317.1 17.1 0.776 0.043 total I 7249 I | 8795 | 100 | 6 | 872 | 2~ nor-hyodeoxy | 15281 | 1 | 15281 | 15281 04-12-2006 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 Page A71 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 | 1:5-13 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 5.1 area 279 1398 233 1493 1698 1962 138 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 385.02 1398 273 1493 1833.84 2904 138 % 4.6 16.6 3.2 17.7 21.8 34.5 1.6 |jg bile acid 0.194 0.706 0.138 0.754 0.926 1.466 0.070 ng bile acid/ mg feces 38.1 138.4 27.0 147.8 181.5 287.4 13.7 nmol bile acid/ mg feces 0.093 0.352 0.066 0.392 0.444 0.703 0.035 total | 7201 | | 8424 | 100 | 4 | 834 | ~ 2 T nor-hyodeoxy | 19809 | 1 | 19809 | 19809 | 1:5-14 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 5.9 area 273 1027 1007 1318 1369 1924 193 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 376.74 1027 1178 1318 1478.52 2848 193 % 4.5 12.2 14.0 15.7 17.6 33.8 2.3 |jg bile acid 0.202 0.550 0.631 0.706 0.792 1.526 0.103 ng bile acid/ mg feces 34.2 93.3 107.0 119.7 134.3 258.6 17.5 nmol bile acid/ mg feces 0.084 0.238 0.262 0.318 0.329 0.633 0.045 total | 7111 | | 8419 | 100 | 5 | 764 | " T ? nor-hyodeoxy | 18666 | 1 | 18666 | 18666 | 1:5-15 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 6.6 area 201 976 457 1197 374 2027 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 277.38 976 535 1197 403.92 3000 0 % 4.3 15.3 8.4 18.7 6.3 47.0 0.0 |jg bile acid 0.239 0.842 0.461 1.033 0.349 2.589 0.000 ng bile acid/ mg feces 36.3 127.6 69.9 156.5 52.8 392.3 0.0 nmol bile acid/ mg feces 0.089 0.325 0.171 0.416 0.129 0.960 0.000 total | 5232 | | 6389 | 100 | 6 | 836 | ~ 2 T nor-hyodeoxy | 11586 | 1 | 11586 | 11586 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 Page A72 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 | 2:5-13 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 6.9 area 170 421 188 1014 816 778 196 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 234.6 421 220 1014 881.28 1151 196 % 5.7 10.2 5.3 24.6 21.4 28.0 4.8 |jg bile acid 0.289 0.519 0.271 1.249 1.086 1.418 0.241 ng bile acid/ mg feces 41.9 75.2 39.3 181.0 157.3 205.6 35.0 nmol bile acid/ mg feces 0.103 0.191 0.096 0.481 0.385 0.503 0.089 total | 3583 | | 4118 | 100 | 5 | 735 | nor-hyodeoxy | 8118 | 1 | 8118 | 8118 | 2:5-14 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 7.1 area 488 1599 1339 1652 2345 2835 357 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 673.44 1599 1567 1652 2532.6 4196 357 % 5.4 12.7 12.5 13.1 20.1 33.4 2.8 |jg bile acid 0.342 0.812 0.795 0.838 1.285 2.130 0.181 ng bile acid/ mg feces 48.1 114.3 112.0 118.1 181.0 299.9 25.5 nmol bile acid/ mg feces 0.118 0.291 0.274 0.314 0.443 0.734 0.065 total | 10615 | | 12576 | 100 | 6 | 899 | ~ 2 T nor-hyodeoxy | 19702 | 1 | 19702 | 19702 | 2:5-15 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 5.4 area 1147 3831 1371 3141 2207 7603 531 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 1582.86 3831 1604 3141 2383.56 11252 531 % 6.5 15.7 6.6 12.9 9.8 46.3 2.2 |jg bile acid 0.461 1.115 0.467 0.914 0.694 3.275 0.155 ng bile acid/ mg feces 85.3 206.5 86.5 169.3 128.5 606.5 28.6 nmol bile acid/ mg feces 0.209 0.526 0.212 0.450 0.314 1.484 0.073 total | 19831 | | 24326 | 100 | 7 | 1311 | ~ 3 ^ nor-hyodeoxy | 34357 | 1 | 34357 | 34357 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 Page A73 of A172 Appendix to TNO-report of 3M-02 Final version 3:5-13_________________________ weight feces 7.9 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 608 1723 925 1896 2481 3000 400 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 839.04 1723 1082 1896 2679.48 4440 400 % 6.4 13.2 8.3 14.5 20.5 34.0 3.1 |jg bile acid 0.282 0.580 0.364 0.638 0.901 1.493 0.135 ng bile acid/ mg feces 35.7 73.4 46.1 80.7 114.1 189.0 17.0 nmol bile acid/ mg feces 0.087 0.187 0.113 0.214 0.279 0.463 0.043 total I 11033 ] I 13060 | 100 | 4 | 556 | ~ nor-hyodeoxy | 29729 | 1 | 29729 | 29729 3:5-14_________________________ weight feces 8.1 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 391 1007 1069 799 1999 2126 548 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 539.58 1007 1251 799 2158.92 3146 548 % 5.7 10.7 13.2 8.5 22.8 33.3 5.8 jg bile acid 0.264 0.493 0.613 0.391 1.058 1.542 0.268 ng bile acid/ mg feces 32.6 60.9 75.7 48.3 130.6 190.3 33.1 nmol bile acid/ mg feces 0.080 0.155 0.185 0.128 0.320 0.466 0.084 total I 7939 1 | 9450 | 100 | 5 | 572 | ~ nor-hyodeoxy | 20411 | 1 | 20411 | 20411 3:5-15 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 7.3 area 908 3513 1190 2079 2885 6815 481 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 1253.04 3513 1392 2079 3115.8 10086 481 % 5.7 16.0 6.4 9.5 14.2 46.0 2.2 jg bile acid 0.363 1.019 0.404 0.603 0.903 2.924 0.139 ng bile acid/ mg feces 49.8 139.5 55.3 82.6 123.7 400.6 19.1 nmol bile acid/ mg feces 0.122 0.355 0.135 0.219 0.303 0.980 0.049 total | 17871 1 | 21920 | 100 | 6 | 871 | 2T nor-hyodeoxy | 34491 | 1 | 34491 | 34491 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 04-12-2006 Page A74 of A172 Appendix to TNO-report of 3M-02 Final version 1:6-16 weight feces 5.8 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 222 654 724 565 752 1281 123 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 306.36 654 847 565 812.16 1896 123 % 5.9 12.6 16.3 10.9 15.6 36.4 2.4 |jg bile acid 0.188 0.401 0.519 0.346 0.498 1.162 0.075 ng bile acid/ mg feces 32.4 69.1 89.5 59.7 85.8 200.4 13.0 nmol bile acid/ mg feces 0.079 0.176 0.219 0.159 0.210 0.490 0.033 total I 4321 I I 5203 | 100 | 3 | 550 | T ? nor-hyodeoxy | 16312 | 1 | 16312 | 16312 1:6-17 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 6.2 area 199 543 411 518 383 1077 111 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 274.62 543 481 518 413.64 1594 111 % 7.0 13.8 12.2 13.2 10.5 40.5 2.8 jg bile acid 0.250 0.494 0.438 0.472 0.377 1.451 0.101 ng bile acid/ mg feces 40.3 79.7 70.6 76.1 60.7 234.1 16.3 nmol bile acid/ mg feces 0.099 0.203 0.173 0.202 0.149 0.573 0.042 total I 3242 I | 3935 | 100 | 4 | 578 | T ? nor-hyodeoxy I 10983 | 1 | 10983 | 10983 1:6-18 weight feces 6.3 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 117 650 962 598 677 1575 174 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 161.46 650 1126 598 731.16 2331 174 % 2.8 11.3 19.5 10.4 12.7 40.4 3.0 jg bile acid 0.120 0.483 0.837 0.444 0.543 1.732 0.129 ng bile acid/ mg feces 19.0 76.7 132.8 70.5 86.3 275.0 20.5 nmol bile acid/ mg feces 0.047 0.195 0.325 0.187 0.211 0.673 0.052 total I 4753 I | 5771 | 100 | 4 | 681 | T 7 nor-hyodeoxy I 13455 | 1 | 13455 | 13455 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 04-12-2006 Page A75 of A172 Appendix to TNO-report of 3M-02 Final version 2:6-16 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 5.6 area 215 821 747 598 840 1244 226 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 296.7 821 874 598 907.2 1841 226 % 5.3 14.8 15.7 10.7 16.3 33.1 4.1 |jg bile acid 0.169 0.469 0.499 0.341 0.518 1.051 0.129 ng bile acid/ mg feces 30.2 83.7 89.1 60.9 92.5 187.6 23.0 nmol bile acid/ mg feces 0.074 0.213 0.218 0.162 0.226 0.459 0.059 total I 4691 I | 5564 | 100 | 3 | 567 | ~ nor-hyodeoxy | 17522 | 1 | 17522 | 17522 2:6-17 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 5.5 area 196 966 220 486 177 733 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 270.48 966 257 486 191.16 1085 0 % 8.3 29.7 7.9 14.9 5.9 33.3 0.0 |jg bile acid 0.241 0.862 0.230 0.434 0.171 0.968 0.000 ng bile acid/ mg feces 43.9 156.7 41.8 78.8 31.0 176.0 0.0 nmol bile acid/ mg feces 0.107 0.399 0.102 0.209 0.076 0.431 0.000 total I 2778 I | 3256 | 100 | 3 | 528 | ~ nor-hyodeoxy | 11207 | 1 | 11207 | 11207 2:6-18 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 7.4 area 553 1729 1319 1154 1500 3330 318 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 763.14 1729 1543 1154 1620 4928 318 % 6.3 14.3 12.8 9.6 13.4 40.9 2.6 |jg bile acid 0.365 0.827 0.738 0.552 0.775 2.358 0.152 ng bile acid/ mg feces 49.3 111.8 99.8 74.6 104.7 318.6 20.6 nmol bile acid/ mg feces 0.121 0.285 0.244 0.198 0.256 0.780 0.052 total I 9903 I I 12056 | 100 | 6 | 779 | ~ nor-hyodeoxy | 20902 | 1 | 20902 | 20902 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 04-12-2006 Page A76 of A172 Appendix to TNO-report of 3M-02 Final version 3:6-16 weight feces 7.4 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 621 1219 1628 685 1439 1866 253 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 856.98 1219 1905 685 1554.12 2762 253 % 9.3 13.2 20.6 7.4 16.8 29.9 2.7 |jg bile acid 0.369 0.525 0.820 0.295 0.669 1.189 0.109 ng bile acid/ mg feces 49.9 70.9 110.8 39.9 90.4 160.7 14.7 nmol bile acid/ mg feces 0.122 0.181 0.271 0.106 0.221 0.393 0.038 total I 7711 I I 9235 | 100 | 4 | 537 | " T ? nor-hyodeoxy | 23222 | 1 | 23222 | 23222 3:6-17 weight feces 8.1 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 829 1831 1171 653 1120 4227 295 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 1144.02 1831 1370 653 1209.6 6256 295 % 9.0 14.4 10.7 5.1 9.5 49.0 2.3 jg bile acid 0.427 0.683 0.511 0.243 0.451 2.332 0.110 ng bile acid/ mg feces 52.7 84.3 63.1 30.1 55.7 288.0 13.6 nmol bile acid/ mg feces 0.129 0.215 0.154 0.080 0.136 0.705 0.035 total I 10126 I I 12759 | 100 | 5 | 587 | nor-hyodeoxy I 26821 | 1 | 26821 | 26821 3:6-18 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 7.7 area 441 1194 995 999 934 1799 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 608.58 1194 1164 999 1008.72 2663 0 % 8.0 15.6 15.2 13.1 13.2 34.9 0.0 jg bile acid 0.253 0.497 0.484 0.416 0.420 1.108 0.000 ng bile acid/ mg feces 32.9 64.5 62.9 54.0 54.5 143.9 0.0 nmol bile acid/ mg feces 0.080 0.164 0.154 0.143 0.133 0.352 0.000 total I 6362 I | 7637 | 100 | 3 | 413 | ~ T nor-hyodeoxy I 24030 | 1 | 24030 | 24030 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 04-12-2006 Page A77 of A172 Appendix to TNO-report of 3M-02 Final version 1:7-19_________________________ weight feces 5.2 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 493 1997 1424 376 1518 1175 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 680.34 1997 1666 376 1639.44 1739 0 % 8.4 24.7 20.6 4.6 20.2 21.5 0.0 |jg bile acid 0.556 1.631 1.361 0.307 1.339 1.421 0.000 ng bile acid/ mg feces 106.9 313.7 261.7 59.1 257.6 273.2 0.0 nmol bile acid/ mg feces 0.262 0.799 0.641 0.157 0.630 0.669 0.000 total | 6983 | | 8098 | 100 | 7 | 1272 | ~ nor-hyodeoxy | 12241 | 1 | 12241 | 12241 1:7-20_________________________ weight feces 5.8 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 602 895 817 302 659 977 267 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 830.76 895 956 302 711.72 1446 267 % 15.4 16.5 17.7 5.6 13.2 26.7 4.9 |jg bile acid 0.725 0.781 0.834 0.264 0.621 1.262 0.233 ng bile acid/ mg feces 125.0 134.7 143.8 45.4 107.1 217.6 40.2 nmol bile acid/ mg feces 0.306 0.343 0.352 0.121 0.262 0.533 0.102 total | 4519 | | 5408 | 100 | 5 | 814 | ~ nor-hyodeoxy | 11457 | 1 | 11457 | 11457 1:7-21 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 5.4 area 512 1419 1545 649 893 912 204 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 706.56 1419 1808 649 964.44 1350 204 % 10.0 20.0 25.5 9.1 13.6 19.0 2.9 |jg bile acid 0.525 1.055 1.344 0.482 0.717 1.003 0.152 ng bile acid/ mg feces 97.3 195.3 248.8 89.3 132.8 185.8 28.1 nmol bile acid/ mg feces 0.238 0.498 0.609 0.237 0.325 0.455 0.072 total | 6134 | nor-hyodeoxy | 13452 | | 1| 7100 13452 | 100 | 5 | 977 | ~ | 13452 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 04-12-2006 Page A78 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 2:7-19__________________________ weight feces 5.5 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 216 631 176 110 543 386 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 298.08 631 206 110 586.44 571 0 % 12.4 26.3 8.6 4.6 24.4 23.8 0.0 |jg bile acid 0.542 1.148 0.375 0.200 1.067 1.039 0.000 ng bile acid/ mg feces 98.6 208.7 68.1 36.4 194.0 189.0 0.0 nmol bile acid/ mg feces 0.241 0.532 0.167 0.097 0.475 0.463 0.000 total | 2062 | | 2403 | 100 | 4 | 795 | T nor-hyodeoxy | 5496 | 1 | 5496 | 5496 2:7-20__________________________ weight feces 5.9 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 872 3015 1451 382 2004 3004 653 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 1203.36 3015 1698 382 2164.32 4446 653 % 8.9 22.2 12.5 2.8 16.0 32.8 4.8 |jg bile acid 0.443 1.110 0.625 0.141 0.797 1.637 0.240 ng bile acid/ mg feces 75.1 188.2 106.0 23.8 135.1 277.5 40.8 nmol bile acid/ mg feces 0.184 0.479 0.259 0.063 0.331 0.679 0.104 total | 11381 | | 13561 | 100 | 5 | 846 | ~~2T nor-hyodeoxy | 27158 | 1 | 27158 | 27158 2:7-21 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 5.3 area 665 3474 1201 397 1600 2024 155 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 917.7 3474 1405 397 1728 2996 155 % 8.3 31.4 12.7 3.6 15.6 27.1 1.4 |jg bile acid 0.585 2.215 0.896 0.253 1.102 1.910 0.099 ng bile acid/ mg feces 110.4 418.0 169.1 47.8 207.9 360.4 18.6 nmol bile acid/ mg feces 0.270 1.065 0.414 0.127 0.509 0.882 0.047 total | 9516 | | 11072 | 100 | 7 | 1332 | ~ 3 ^ nor-hyodeoxy | 15683 | 1 | 15683 | 15683 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 Page A79 of A172 Appendix to TNO-report of 3M-02 Final version 3:7-19_________________________ weight feces 6.7 mg a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso area 535 850 877 325 1150 921 605 response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 738.3 850 1026 325 1242 1363 605 % 12.0 13.8 16.7 5.3 20.2 22.2 9.8 |jg bile acid 0.631 0.726 0.877 0.278 1.061 1.164 0.517 ng bile acid/ mg feces 94.1 108.4 130.8 41.4 158.4 173.8 77.1 nmol bile acid/ mg feces 0.230 0.276 0.320 0.110 0.388 0.425 0.196 total I 5263 ! nor-hyodeoxy | 11706 | | 1| 6149 11706 | 100 | 5 | 784 | | 11706 1.9 3:7-20_________________________ weight feces 6.5 mg oppervlakte a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 290 571 462 258 300 422 response factor 1.38 1 1 1 1.08 1 1 oppervlakte 400.2 571 541 258 324 625 0 % 14.7 21.0 19.9 9.5 11.9 23.0 0.0 jg bile acid 0.950 1.355 1.283 0.612 0.769 1.482 0.000 ng bile acid/ mg faeces 146.1 208.5 197.3 94.2 118.3 228.0 0.0 nmol bile acid/ mg faeces 0.358 0.531 0.483 0.250 0.289 0.558 0.000 total | 2303 1 | nor-hyodeoxy | 4214 | 1 | 2718 4214 | 100 | 6 | 992 | | 4214 2.5 3:7-21 weight feces a-muricholate deoxycholate cholate lithocholate B-muricholate w-muricholate hyodeo/urso 7.2 area 1184 3208 2501 1182 3049 3105 1201 mg response factor 1.38 1 1 1 1.08 1 1 area corrected for response factor 1633.92 3208 2926 1182 3292.92 4595 1201 % 9.1 17.8 16.2 6.6 18.3 25.5 6.7 jg bile acid 0.503 0.987 0.900 0.364 1.013 1.414 0.370 ng bile acid/ mg feces 69.8 137.1 125.1 50.5 140.7 196.4 51.3 nmol bile acid/ mg feces 0.171 0.349 0.306 0.134 0.344 0.481 0.131 total | 15430 1 | 18039 | 100 | 6 | 771 | 1.9 nor-hyodeoxy | 32495 | 1 | 32495 | 32495 a-muri deoxy cholate lithochol b-muri w-muri hyodeoxy/urso 408.6 392.6 408.6 376.6 408.6 408.6 392.6 04-12-2006 Page A80 of A172 Appendix to TNO-report of 3M-02____________ Final version__________________________04-12-2006 Page A81 of A172 group 1 AVERAGE SD 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 AVERAGE SD cage# 1,2 3 ,4 5 1,2 3 ,4 5 1,2 3 ,4 5 6 7 ,8 9,1 0 6 7 ,8 9,1 0 6 7 ,8 9,1 0 1 1 ,1 2 ,1 3 15 1 4 ,1 6 ,1 7 1 1 ,1 2 ,1 3 15 1 4 ,1 6 ,1 7 1 1 ,1 2 ,1 3 15 1 4 ,1 6 ,1 7 18 19 20 ,2 1 18 19 20 ,2 1 18 19 20 ,2 1 22 2 4 ,2 5 2 3 ,2 6 ,2 7 22 2 4 ,2 5 2 3 ,2 6 ,2 7 22 2 4 ,2 5 2 3 ,2 6 ,2 7 2 8 ,2 9 31 3 0 ,3 2 2 8 ,2 9 31 3 0 ,3 2 2 8 ,2 9 31 3 0 ,3 2 3 3 ,3 4 ,3 5 3 6 ,3 7 3 8 ,3 9 3 3 ,3 4 ,3 5 3 6 ,3 7 3 8 ,3 9 3 3 ,3 4 ,3 5 3 6 ,3 7 3 8 ,3 9 GC sa m p le # 1:1-1 1 :1 -2 1 :1 -3 2:1-1 2:1 -2 2:1 -3 3:1-1 3:1 -2 3:1 -3 a -m u ric h o la te 0.18 9 0.11 3 0.12 0 0.31 9 0.16 0 0.21 7 0.11 2 0.12 0 0.17 2 d e o x y c h o la te 0.53 2 0.27 4 0 .3 1 1 0.52 8 0.30 5 0.36 6 0.76 4 0.29 8 0.33 0 1 :2 -4 1 :2 -5 1 :2 -6 2:2 -4 2:2 -5 2:2 -6 3:2 -4 3:2 -5 3:2 -6 0.08 2 0.08 0 0.15 0 0.16 5 0.14 5 0.23 8 0.14 9 0 .1 2 1 0.20 4 0.34 5 0.27 8 0.49 6 0.39 6 0 .2 6 1 0.55 9 0.37 7 0.24 9 0.50 8 1 :3 -7 1 :3 -8 1 :3 -9 2:3 -7 2:3 -8 2:3 -9 3:3 -7 3:3 -8 3:3 -9 0.11 9 0.10 2 0.15 8 0.06 8 0.10 0 0.15 4 0.11 3 0 .1 0 1 0.13 3 0.42 0 0.44 3 0.39 7 0.43 7 0.26 9 0.32 6 0.35 6 0.25 9 0.35 2 1 :4-10 1 :4 -1 1 1 :4-12 2 :4 -1 0 2 :4 -1 1 2 :4 -1 2 3 :4 -1 0 3 :4 -1 1 3 :4 -1 2 0.05 5 0 .2 3 1 0.15 9 0.10 2 0.18 9 0.17 9 0.09 3 0.14 0 0.14 6 0.14 2 0.25 0 0.32 0 0.22 3 0 .1 9 1 0.22 4 0.17 4 0.26 4 0.21 0 1 :5-13 1 :5-14 1 :5-15 2 :5 -1 3 2 :5 -1 4 2 :5 -1 5 3 :5 -1 3 3 :5 -1 4 3 :5 -1 5 0.09 3 0.08 4 0.08 9 0.10 3 0.11 8 0.20 9 0.08 7 0.08 0 0.12 2 0.35 2 0.23 8 0.32 5 0 .1 9 1 0 .2 9 1 0.52 6 0.18 7 0.15 5 0.35 5 1 :6-16 1 :6-17 1 :6-18 2 :6 -1 6 2 :6 -1 7 2 :6 -1 8 3 :6 -1 6 3 :6 -1 7 3 :6 -1 8 0.07 9 0.09 9 0.04 7 0.07 4 0.10 7 0 .1 2 1 0.12 2 0.12 9 0.08 0 0.17 6 0.20 3 0.19 5 0.21 3 0.39 9 0.28 5 0 .1 8 1 0.21 5 0.16 4 1 :7-19 1 :7-20 1 :7 -2 1 2 :7 -1 9 2 :7 -2 0 2 :7 -2 1 3 :7 -1 9 3 :7 -2 0 3 :7 -2 1 0.26 2 0.30 6 0.23 8 0 .2 4 1 0.18 4 0.27 0 0.23 0 0.35 8 0 .1 7 1 0.79 9 0.34 3 0.49 8 0.53 2 0.47 9 1.06 5 0.27 6 0 .5 3 1 0.34 9 bile acid s (um o l/g feces) c h o la te lith o c h o l a te b -m u ric h o la te w -m u ric h o la te h y o d e o /u rs o 0.17 4 0.27 2 0.69 7 1 .0 1 2 0.07 6 0.22 7 0.40 5 0.40 7 1 .4 3 5 0.04 6 0.17 9 0.41 3 0.40 6 1 .2 8 0 0.05 7 0.18 4 0.26 8 0.63 9 0.55 3 0.00 0 0.31 7 0.33 9 0.55 8 1 .5 5 7 0.02 5 0 .4 1 1 0.09 6 0.64 5 1 .2 2 9 0.02 9 0.12 9 0 .1 4 1 0.79 7 0.97 6 0.03 9 0 .1 6 1 0.22 7 0.29 7 0.17 6 0.37 6 0.62 8 1 .0 5 9 1 .0 3 8 0.03 8 0.06 9 bile a cid s to ta l (um ol/g feces) 2.9 5 2 .9 1 2.7 7 2.4 9 3.2 6 2.9 9 2.9 6 2.3 5 2.6 4 to ta l feces (g) 3.07 5 2 .48 97 2 .29 46 4.69 2 3 .77 89 3 .41 06 3 .57 54 2 .8 7 8 1 2 .75 89 a ve rag e w eig ht days (g) 12 3.6 8 7 .2 5 8 8 .5 5 1 2 2.45 8 6 .5 5 8 8 .2 1 2 1.65 8 6 .5 5 8 8 .0 5 2 2 2 3 3 3 2 2 2 0.25 5 0.25 2 0.27 5 0.22 9 0.18 2 0.29 2 0.25 5 0.20 0 0.35 6 0.24 7 0.32 2 0.56 6 0.29 8 0.33 0 0.46 7 0.20 9 0.19 6 0.36 8 0.36 6 0 .8 2 1 0.46 7 0.44 0 0.72 3 0.47 4 0.62 3 0.73 5 0.53 8 1 .1 6 2 0.94 4 1 .7 3 4 1 .2 1 9 1 .1 1 8 1 .7 1 7 1 .3 7 0 0.88 3 1 .5 6 9 0.06 2 0.02 4 0.05 9 0.00 0 0.06 8 0.06 4 0.06 7 0.07 6 0.09 3 2.5 2 2.7 2 3.7 5 2.7 5 2.8 3 3 .8 1 3.0 5 2.4 6 3.6 4 2 .76 19 4 .0 5 8 1 2 .09 35 4.07 5 6 .3 7 1 3 .40 74 2 .92 79 4 .39 85 2 .45 75 9 4 .5 5 12 6.6 8 2 .2 9 4 .2 5 1 2 6.45 82 .1 94 12 6.6 8 1 .8 5 2 2 2 3 3 3 2 2 2 0.12 2 0.19 3 0.23 4 0.29 0 0 .2 3 1 0.28 6 0.16 7 0.15 8 0.20 8 0.50 7 0.52 0 0.59 3 0.52 3 0.37 3 0.06 6 0.24 2 0.27 9 0.34 7 0 .6 2 1 0.47 6 0.69 5 0.59 9 0.39 0 0.64 3 0.53 9 0.38 0 0 .6 8 1 1 .5 1 3 1 .4 4 6 1 .2 1 9 1 .3 7 5 1 .0 8 4 0.90 7 0 .8 9 1 0.96 0 1 .0 4 9 0.05 2 0.06 3 0.00 0 0.08 9 0.04 6 0.00 0 0.04 7 0.03 8 0.03 7 3.3 6 3.2 4 3.3 0 3.3 8 2.4 9 2.3 8 2.3 5 2.1 8 2 .8 1 3 .45 97 2 .29 94 2 .34 54 5 .81 47 3 .77 18 3 .77 27 4.02 5 2 .52 65 2 .69 05 118 8 3 .5 5 8 2 .8 1 1 8.75 8 3 .5 8 3 .0 5 11 9.6 8 4 .2 8 3 .4 5 2 2 2 3 3 3 2 2 2 0.12 9 0 .1 3 1 0.20 0 0.29 8 0.16 5 0.32 9 0.15 5 0.08 4 0.33 6 0.16 4 0 .1 4 1 0.37 3 0.31 5 0.21 5 0.26 4 0.14 6 0.15 5 0.18 2 0.14 5 0.36 4 0.37 2 0.21 6 0.44 4 0.41 8 0 .2 3 1 0.46 9 0.46 5 0.67 4 0.80 6 1 .0 9 9 0.66 4 0.90 2 0.92 6 0.62 7 0.76 5 0.77 6 0.09 4 0.00 0 0.00 0 0.00 0 0 .0 8 1 0 .0 5 1 0.04 6 0.05 7 0.04 3 1 .4 0 1 .9 2 2.5 2 1 .8 2 2.1 9 2.3 9 1 .4 7 1 .9 3 2.1 6 1.68 9 3 .14 32 3 .25 45 2 .71 33 4 .64 07 5 .20 75 2 .0 4 1 3 .44 64 3 .95 49 5 9 .5 11 6.4 11 2.2 5 8 .8 5 1 1 6.55 1 1 1.85 5 8 .7 1 1 7.45 11 2.9 2 2 2 3 3 3 2 2 2 0.06 6 0.26 2 0 .1 7 1 0.09 6 0.27 4 0.21 2 0.11 3 0.18 5 0.13 5 0.39 2 0.31 8 0.41 6 0 .4 8 1 0.31 4 0.45 0 0.21 4 0.12 8 0.21 9 0.44 4 0.32 9 0.12 9 0.38 5 0.44 3 0.31 4 0.27 9 0.32 0 0.30 3 0.70 3 0.63 3 0.96 0 0.50 3 0.73 4 1 .4 8 4 0.46 3 0.46 6 0.98 0 0.03 5 0.04 5 0.00 0 0.08 9 0.06 5 0.07 3 0.04 3 0.08 4 0.04 9 2.0 9 1.91 2.0 9 1 .8 5 2.2 4 3.2 7 1 .3 9 1 .4 2 2.1 6 3.19 5 2 .94 08 2 .63 99 4 .97 12 4 .48 33 3.76 7 3 .61 13 3 .35 22 2 .70 34 11 0.7 8 8 .3 5 8 4 .6 11 1.6 8 8 .5 8 5 .5 5 1 1 2.85 8 8 .9 8 5 .5 2 2 2 3 3 3 2 2 2 0.21 9 0.17 3 0.32 5 0.21 8 0.10 2 0.24 4 0 .2 7 1 0.15 4 0.15 4 0.15 9 0.20 2 0.18 7 0.16 2 0.20 9 0.19 8 0.10 6 0.08 0 0.14 3 0.21 0 0.14 9 0 .2 1 1 0.22 6 0.07 6 0.25 6 0 .2 2 1 0.13 6 0.13 3 0.49 0 0.57 3 0.67 3 0.45 9 0 .4 3 1 0.78 0 0.39 3 0.70 5 0.35 2 0.03 3 0.04 2 0.05 2 0.05 9 0.00 0 0.05 2 0.03 8 0.03 5 0.00 0 1 .3 7 1 .4 4 1 .6 9 1.41 1 .3 2 1 .9 4 1 .3 3 1 .4 5 1 .0 3 2 .50 36 2 .70 83 2 .35 54 3 .96 84 3 .96 78 3 .56 66 2 .90 76 3 .24 49 2 .76 43 87 .1 11 2.8 8 5 .4 8 7 .1 5 1 1 2.45 8 4 .5 5 8 7 .6 5 1 1 1.95 8 4 .6 5 2 2 2 3 3 3 2 2 2 0 .6 4 1 0.35 2 0.60 9 0.16 7 0.25 9 0.41 4 0.32 0 0.48 3 0.30 6 0.15 7 0 .1 2 1 0.23 7 0.09 7 0.06 3 0.12 7 0.11 0 0.25 0 0.13 4 0.63 0 0.26 2 0.32 5 0.47 5 0 .3 3 1 0.50 9 0.38 8 0.28 9 0.34 4 0.66 9 0.53 3 0.45 5 0.46 3 0.67 9 0.88 2 0.42 5 0.55 8 0 .4 8 1 0.00 0 0.10 2 0.07 2 0.00 0 0.10 4 0.04 7 0.19 6 0.00 0 0 .1 3 1 3.1 6 2.0 2 2.4 3 1 .9 7 2.1 0 3 .3 1 1 .9 5 2.4 7 1 .9 2 1.96 97 2 .07 98 2 .67 05 3 .44 77 3 .26 46 4 .30 59 2 .51 17 2 .43 69 3 .41 07 8 1 .3 5 8 2 .2 5 1 0 1.05 8 2 .3 5 8 2 .7 5 1 0 1.95 8 3 .5 8 3 .3 5 10 3.2 2 2 2 3 3 3 2 2 2 to tal b ile acid excre tion (um ol/1 00 gr m ou se/d ay) 3 .6 7 4 .1 5 3 .5 8 3 .1 8 4 .7 5 3 .8 6 4 .3 5 3 .9 0 4 .1 4 3 .9 5 0 .4 6 3 .6 8 4 .3 6 4 .7 7 3 .9 6 4 .7 5 5 .2 7 4 .7 5 4 .2 7 5 .4 6 4 .5 9 0 .5 8 4 .9 2 4 .4 6 4 .6 7 5 .5 2 3 .7 5 3.61 3 .9 6 3 .2 6 4 .5 3 4 .3 0 0.71 1 .9 9 2 .6 0 3 .6 6 2 .7 9 2 .9 0 3.71 2 .5 6 2 .8 4 3 .7 8 2 .9 8 0.61 3.01 3 .1 7 3 .2 6 2 .7 4 3 .7 8 4 .8 0 2 .2 2 2 .6 7 3 .4 2 3 .2 3 0 .7 4 1 .9 6 1 .7 3 2 .3 3 2 .1 4 1 .5 6 2 .7 2 2.21 2.11 1 .6 8 2 .0 5 0 .3 6 3 .8 2 2 .5 5 3 .2 2 2 .7 5 2 .7 6 4 .6 7 2 .9 3 3.61 3 .1 7 3 .2 7 0 .6 7 % o f b ile acid s 1 a -m u ric h o la te d e o x y c h o la te c h o la te lith o c h o la te b -m u ric h o la te w -m u ric h o la te h y o d e o /u rs o 6.3 9 1 8 .0 3 5.8 9 9 .2 1 23 .6 1 3 4 .3 0 2 .5 7 3.8 7 4.3 3 9.4 2 1 1 .2 4 7.8 0 6.4 6 1 3 .9 5 1 4 .9 4 1 4 .0 0 1 4 .6 8 4 9 .3 7 4 6 .2 9 1 .5 8 2 .0 6 12 .8 2 2 1 .1 9 7.3 7 1 0 .7 5 2 5 .6 6 2 2 .2 0 0 .0 0 4.9 2 9.3 4 9 .7 1 10 .4 1 1 7 .1 0 4 7 .7 5 0 .7 8 7.2 4 3.7 8 1 2 .2 3 2 5 .8 5 1 3 .7 5 4.3 7 3.2 2 4.7 6 2 1 .5 4 2 6 .9 4 4 1 .0 6 3 2 .9 9 0 .9 7 1 .3 2 5.1 3 6.5 3 1 2 .6 8 12 .5 1 6.8 4 8.6 0 1 2 .6 3 6.6 6 1 6 .0 0 2 3 .7 8 45 .1 1 3 9 .3 2 1.61 2 .6 0 6 .1 1 2.8 0 1 4 .7 2 5 .7 1 7.8 7 2.6 9 9 .6 1 4.0 5 2 0 .3 7 4.9 7 3 9 .8 2 8.7 5 1 .5 0 0 .8 5 3.2 6 1 3 .6 9 1 0 .1 3 9.8 0 1 4 .5 3 4 6 .1 3 2 .4 6 2.9 3 1 0 .2 3 9.2 6 1 1 .8 4 3 0 .1 7 3 4 .7 0 0 .8 7 4.0 0 6.0 0 1 3 .2 4 1 4 .4 3 7.3 5 8.3 3 15 .1 1 1 0 .8 5 1 2 .4 6 1 6 .0 2 4 6 .2 8 4 4 .3 8 1 .5 7 0 .0 0 5.1 3 9.2 5 6.4 3 1 1 .6 6 2 5 .5 8 3 9 .5 7 2 .3 9 6.2 6 1 4 .6 7 7.6 5 1 2 .2 6 1 2 .4 4 4 5 .0 4 1 .6 7 4.8 7 1 2 .3 6 8.3 6 6.8 6 2 0 .4 3 4 4 .9 2 2 .1 9 4 .9 1 5 .6 1 10 .1 1 1 3 .9 8 8.1 5 9.7 8 7.9 8 1 0 .1 2 2 9 .8 8 1 4 .7 8 3 5 .9 0 4 3 .1 6 3 .0 8 2 .5 6 4.7 7 1 .1 6 1 2 .4 4 2.0 6 8.3 8 1 .1 9 1 0 .7 2 2.4 3 1 9 .5 9 7.2 3 4 2 .2 3 4.4 2 1 .8 6 0 .9 5 3.5 6 12 .5 1 3.6 5 15 .1 1 1 8 .5 2 4 5 .1 0 1 .5 6 3.1 6 4 .8 1 1 3 .6 6 1 2 .0 4 5.9 4 7.0 9 1 6 .0 4 1 8 .0 0 1 4 .6 6 2 1 .0 8 4 4 .5 8 3 6 .9 9 1 .9 6 0 .0 0 2.0 2 1 2 .9 3 8.5 9 1 5 .4 8 1 7 .7 2 4 0 .6 5 2 .6 2 4.0 3 10 .8 1 9.2 6 1 4 .9 7 1 5 .6 3 4 3 .4 6 1 .8 5 6.4 6 4 .8 1 13 .7 1 1 5 .1 2 1 2 .0 2 7.0 9 2.7 6 1 0 .2 7 2 6 .9 8 2 2 .8 9 3 8 .0 7 3 7 .8 2 0 .0 0 2 .0 0 4.6 4 4.7 5 1 1 .9 2 1 2 .5 3 7.2 6 7 .4 1 1 2 .8 4 1 2 .3 7 1 7 .4 6 2 4 .2 6 4 4 .1 3 3 7 .3 7 1 .7 5 1.31 4.2 5 1 .2 6 1 2 .8 0 1 .2 5 7.5 9 2.3 0 1 3 .0 9 4.4 9 19 .9 1 4.1 5 40 .9 1 3.4 2 1 .4 5 0 .9 0 3.9 0 1 0 .1 0 9.1 7 1 1 .7 2 1 0 .3 3 4 8 .0 8 6 .7 0 12 .0 3 1 3 .0 2 6.8 0 7.3 3 1 8 .9 3 4 1 .8 9 0 .0 0 6 .3 1 1 2 .6 7 7.9 4 1 4 .7 9 1 4 .7 3 4 3 .5 5 0 .0 0 5.6 0 8.6 4 1 2 .2 9 8.7 2 1 6 .3 9 7.5 4 17 .3 1 9.8 2 1 1 .8 8 2 0 .3 0 3 6 .5 3 4 1 .2 5 0 .0 0 3 .7 2 7.4 8 9.3 7 1 3 .7 7 1 1 .0 3 1 7 .4 8 3 8 .7 4 2 .1 4 6 .3 1 11 .8 1 1 0 .5 4 9.9 3 1 5 .7 0 42 .6 1 3 .1 0 7.2 4 6.7 6 1 3 .6 4 9.7 2 4.3 4 1 5 .5 5 8.0 2 8.4 5 2 4 .2 7 2 1 .5 4 3 9 .5 3 3 5 .9 6 2 .9 6 2.01 7.1 4 2.2 6 1 1 .2 6 1 .8 0 1 0 .2 3 4.1 7 1 0 .9 4 3.2 8 1 7 .2 4 4.5 5 4 0 .9 0 3.7 5 2 .2 9 2 .1 9 4.4 7 4.3 9 1 6 .8 9 1 2 .4 6 3.1 6 1 3 .7 3 18 .8 1 1 6 .6 7 2 1 .2 9 1 7 .2 3 33 .7 1 3 3 .1 9 1 .6 7 2 .3 4 4.2 5 1 5 .5 5 8.1 9 1 9 .8 9 6.1 9 4 5 .9 4 0 .0 0 5.5 5 1 0 .3 6 5.2 0 26 .0 1 2 0 .8 4 2 7 .2 2 4 .8 2 5.2 6 6.3 9 1 3 .0 0 1 6 .1 0 1 2 .2 4 6.4 8 14 .0 1 1 3 .7 6 1 9 .7 9 9.6 2 3 2 .7 9 4 5 .4 3 2 .9 0 2 .2 3 6 .3 1 1 3 .4 8 8.1 3 1 5 .4 6 2 0 .1 4 3 3 .3 6 3 .1 3 5.6 3 5.6 3 1 0 .9 4 1 6 .4 3 1 3 .0 5 6.2 5 9.0 5 1 0 .1 3 2 2 .5 3 1 4 .0 0 3 2 .8 4 45 .3 1 5 .9 5 2 .2 5 5.3 2 0.8 0 13 .9 1 2.4 3 8.4 9 3.7 2 1 5 .9 7 5.1 9 1 6 .8 5 5.7 2 3 6 .6 4 6.9 6 2.81 1 .7 4 5.8 0 1 2 .8 8 1 6 .0 3 1 1 .6 0 1 5 .3 7 3 5 .8 9 2 .4 2 6.8 6 14 .1 1 1 2 .0 0 1 4 .0 3 1 0 .3 3 3 9 .7 9 2 .8 8 2.7 6 5.2 4 1 1 .5 5 1 5 .1 0 1 9 .2 2 1 5 .4 5 1 1 .0 8 1 1 .4 7 1 2 .4 9 1 6 .0 4 39 .8 1 3 2 .5 4 3 .0 9 4 .1 6 8 .1 1 3 0 .1 3 7 .7 1 1 5 .8 0 5.7 3 32 .5 1 0 .0 0 6.2 4 1 4 .7 0 12 .6 1 1 0 .2 3 1 3 .2 4 4 0 .2 7 2 .7 0 9.1 6 8.8 7 1 3 .5 6 1 4 .7 7 2 0 .3 7 1 0 .6 2 7.9 5 5.4 9 1 6 .6 2 9.3 8 2 9 .5 3 4 8 .4 9 2 .8 2 2 .3 8 7.8 3 1 5 .9 9 1 4 .9 8 1 3 .9 5 1 2 .9 8 3 4 .2 6 0 .0 0 6.7 6 2.0 2 1 5 .8 7 5 .5 1 1 4 .3 3 4.0 4 1 1 .2 9 3.1 8 1 2 .4 6 3 .5 1 37 .0 1 5.7 3 2 .2 7 1 .3 9 8.2 9 15 .1 6 25 .3 1 1 6 .9 9 2 0 .2 9 1 7 .4 4 4.9 7 5.9 8 1 9 .9 7 1 2 .9 8 2 1 .1 8 2 6 .3 8 0 .0 0 5 .0 7 9.7 8 2 0 .4 5 2 5 .0 3 9.7 5 1 3 .3 5 1 8 .6 9 2 .9 4 12 .2 3 2 6 .9 4 8.4 5 4.9 0 2 4 .0 6 2 3 .4 3 0 .0 0 8.7 6 2 2 .8 3 1 2 .3 5 3.0 2 1 5 .7 5 3 2 .3 5 4 .9 5 8.1 5 11 .8 4 3 2 .1 3 1 4 .1 9 1 2 .4 9 1 6 .4 5 3.8 3 5.6 5 1 5 .3 5 1 9 .9 2 2 6 .6 2 2 1 .8 6 1 .4 3 1 0 .1 0 14 .4 8 8.9 2 2 1 .5 0 1 8 .2 3 1 9 .5 6 1 5 .9 7 1 0 .1 3 7.0 0 1 1 .7 2 1 7 .9 7 2 2 .6 0 2 5 .0 8 0 .0 0 6 .8 2 10 .8 4 2.6 9 2 2 .0 6 5.5 0 1 6 .4 5 4.9 5 6.1 4 2.4 5 1 6 .7 9 4.0 2 2 4 .2 4 3.9 7 3 .4 8 3 .5 4 Appendix to TNO-report of 3M-02 Final version 04-12-2006 bile acid total bile acids a-muricholate deoxycholate cholate lithocholate b-muricholate w-muricholate hyodeo/urso bile acid total bile acids a-muricholate deoxycholate cholate lithocholate b-muricholate w-muricholate hyodeo/urso bile acid total bile acids a-muricholate deoxycholate cholate lithocholate b-muricholate w-muricholate hyodeo/urso group 1 vs 2 nn p 9 9 0.019 9 9 0.258 9 9 0.863 9 9 0.340 9 9 0.605 9 9 0.666 9 9 0.931 9 9 0.436 group 2 vs 4 nn p 9 9 <0.001 9 9 0.006 9 9 0.113 9 9 0.546 9 9 0.931 9 9 0.605 9 9 0.387 9 9 0.730 group 3 vs 7 nn p 9 9 0.008 9 9 <0.001 9 9 <0.001 9 9 <0.001 9 9 0.004 9 9 0.161 9 9 <0.001 9 9 0.387 group 1 vs 3 nn p 9 9 0.297 9 9 0.077 9 9 0.931 9 9 1.000 9 9 0.063 9 9 1.000 9 9 0.730 9 9 1.000 group 2 vs 5 nn p 9 9 0.003 9 9 0.297 9 9 0.222 9 9 0.666 9 9 0.019 9 9 0.666 9 9 0.094 9 9 0.258 group 4 vs 5 nn p 9 9 0.489 9 9 0.031 9 9 0.031 9 9 0.340 9 9 0.031 9 9 1.000 9 9 0.161 9 9 0.546 Bile acid excretion, p values Mann-Whitney U-test group 1 vs 4 group 1 vs 5 group 1 vs 6 nn E nn p nn p 9 9 0.003 9 9 0.019 9 9 <0.001 9 9 0.190 9 9 0.863 9 9 0.258 9 9 0.340 9 9 0.796 9 9 0.258 9 9 0.190 9 9 0.931 9 9 0.002 9 9 0.666 9 9 0.019 9 9 0.340 9 9 0.258 9 9 0.190 9 9 0.003 9 9 1.000 9 9 0.258 9 9 0.297 9 9 0.387 9 9 0.040 9 9 0.094 group 2 vs 6 group 2 vs 7 group 3 vs 4 nn p nn p nn p 9 9 <0.001 9 9 0.001 9 9 0.002 9 9 0.024 9 9 <0.001 9 9 0.004 9 9 0.040 9 9 <0.001 9 9 0.094 9 9 0.001 9 9 <0.001 9 9 0.161 9 9 0.730 9 9 0.002 9 9 0.094 9 9 0.077 9 9 0.546 9 9 0.387 9 9 0.063 9 9 <0.001 9 9 0.863 9 9 0.258 9 9 0.546 9 9 0.222 group 4 vs 6 group 4 vs 7 group 5 vs 6 nn p nn p nn p 9 9 0.002 9 9 0.489 9 9 <0.001 9 9 1.000 9 9 0.003 9 9 0.063 9 9 0.003 9 9 <0.001 9 9 0.730 9 9 0.077 9 9 0.011 9 9 0.014 9 9 0.666 9 9 0.003 9 9 0.077 9 9 0.040 9 9 0.796 9 9 0.050 9 9 0.094 9 9 <0.001 9 9 0.931 9 9 0.931 9 9 0.605 9 9 0.931 group 1 vs 7 nn p 9 9 0.019 9 9 0.002 9 9 0.014 9 9 0.001 9 9 0.077 9 9 0.136 9 9 0.001 9 9 0.387 group 3 vs 5 nn p 9 9 0.008 9 9 0.094 9 9 0.340 9 9 0.796 9 9 0.387 9 9 0.340 9 9 0.258 9 9 0.031 group 5 vs 7 nn p 9 9 0.863 9 9 <0.001 9 9 <0.001 9 9 0.002 9 9 <0.001 9 9 0.666 9 9 <0.001 9 9 0.863 group 2 vs 3 nn p 9 9 0.387 9 9 0.258 9 9 1.000 9 9 0.222 9 9 0.040 9 9 0.605 9 9 0.436 9 9 0.340 group 3 vs 6 nn p 9 9 <0.001 9 9 0.008 9 9 0.063 9 9 0.001 9 9 0.161 9 9 0.001 9 9 0.094 9 9 0.050 group 6 vs 7 nn p 9 9 <0.001 9 9 0.002 9 9 0.011 9 9 0.340 9 9 0.002 9 9 0.050 9 9 <0.001 9 9 0.546 p<0.05 Page A82 of A172 Appendix to TNO-report of 3M-02 Final version E3. Fecal sterol measurements 1:1-1 weight feces 6.2 mg area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol coprostanon 1 0 0.0 0.0 0 0.00 1 0 0.0 0.0 0 0.00 cholesterol 284344 0.98 278657 85.2 60.3 9718 25.13 cholestanol lathosterol 9225 10102 0.91 1 8395 10102 2.6 1.8 293 0.75 3.1 2.2 352 0.91 campesterol 4671 1.56 7287 2.2 1.6 254 0.63 stigmasterol 1682 1.49 2506 0.8 0.5 87 0.21 b-sitosterol b-sitostanol 13713 1.47 1 20158 0 6.2 4.4 703 1.70 0.0 0.0 0 0.00 total I 323737 I | 327105 | 100 | 71 | 11407 | 29.3 | cholestane | 11117^ | " | 115625 | ______________________________________115625_____________________________________________ | 1:1-2 ~ weight feces 6.5 mg area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon cholesterol 313994 1 0.98 0 307714 0.0 0.0 0 0.00 86.6 76.7 11803 30.52 cholestanol 9355 0.91 8513 2.4 2.1 327 0.84 lathosterol campesterol 9015 4796 1 1.56 9015 7482 2.5 2.2 346 0.89 2.1 1.9 287 0.72 stigmasterol 1808 1.49 2694 0.8 0.7 103 0.25 b-sitosterol b-sitostanol 13562 1.47 1 19936 0 5.6 5.0 765 1.84 0.0 0.0 0 0.00 total I 352530 | | 355354 | 100 | 89 | 13631 | 35.1 | cholestane | 96413 | 4 | 100270 | 100270_____________________________________________ 1 1 3 ________________________________________________________________________ weight feces 7.1 mg area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon cholesterol cholestanol 298829 8558 1 0.98 0.91 0 292852 7788 0.0 0.0 0 0.00 86.7 73.5 10347 26.76 2.3 2.0 275 0.71 lathosterol campesterol stigmasterol 10265 4356 1589 1 1.56 1.49 10265 6795 2368 3.0 2.6 363 0.94 2.0 1.7 240 0.60 0.7 0.6 84 0.20 b-sitosterol b-sitostanol 12044 1.47 1 17705 0 5.2 4.4 626 1.51 0.0 0.0 0 0.00 total I 335641 | | 337773 | 100 | 85 | 1193^ | 30.7 | cholestane 95828 1.04 99661 99661 coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A83 of A172 Appendix to TNO-report of 3M-02 Final version | 2:1-1 weight feces 7 mg coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol area 319680 11436 10467 5023 1268 13626 response area corrected factor for response factor 10 10 0.98 313286 0.91 10407 1 10467 1.56 7836 1.49 1889 1.47 20030 10 % 0.0 0.0 86.1 2.9 2.9 2.2 0.5 5.5 0.0 pg sterol 0.0 0.0 87.7 2.9 2.9 2.2 0.5 5.6 0.0 ng sterol/ mg feces 0 0 12532 416 419 313 76 801 0 nmol sterol/ mg feces 0.00 0.00 32.41 1.07 1.08 0.78 0.18 1.93 0.00 total | 361500 ! | 363916 | 100 | 102 | 14557 | 37.5 | cholestane | 85850 | 1.04 | | 2:1-2 weight feces 10.4 mg 89284 89284 ~ area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon cholesterol 508256 1 0.98 0 498091 0.0 0.0 0 87.4 131.0 12591 0.00 32.56 cholestanol 15011 0.91 13660 2.4 3.6 345 0.89 lathosterol campesterol 13004 7404 1 1.56 13004 11550 2.3 3.4 329 2.0 3.0 292 0.85 0.73 stigmasterol b-sitosterol b-sitostanol 2781 19988 1.49 1.47 1 4144 29382 0 0.7 1.1 105 0.25 5.2 7.7 743 1.79 0.0 0.0 0 0.00 total | 566444 | | 569831 | 100 | 150 | 14405 | 37.1 | cholestane | 91434 | 1.04 | | 2:1-3 weight feces 6.8 mg 9509~ 95091 ' area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 292666 0.98 286813 86.8 89.9 13215 34.17 cholestanol lathosterol 8651 9600 0.91 1 7872 9600 2.4 2.5 363 2.9 3.0 442 0.93 1.14 campesterol 4193 1.56 6541 2.0 2.0 301 0.75 stigmasterol 1436 1.49 2140 0.6 0.7 99 0.24 b-sitosterol b-sitostanol 11876 1.47 1 17458 0 5.3 5.5 804 0.0 0.0 0 1.94 0.00 total | 328422 | | 330424 | 100 | 104 | 15225 | 39.2 | cholestane 76721 | 1.04 79790 79790 coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A84 of A172 Appendix to TNO-report of 3M-02 Final version 3:1-1____________________ weight feces 6.1 mg area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol coprostanon cholesterol cholestanol lathosterol 440429 13442 11803 1 1 0.98 0.91 1 0 0 431620 12232 11803 0.0 0.0 0 0.00 0.0 0.0 0 0.00 87.6 73.9 12121 31.34 2.5 2.1 344 0.88 2.4 2.0 331 0.86 campesterol 6241 1.56 9736 2.0 1.7 273 0.68 stigmasterol 2114 1.49 3150 0.6 0.5 88 0.21 b-sitosterol b-sitostanol 16460 1.47 1 24196 0 4.9 4.1 679 0.0 0.0 0 1.64 0.00 total I 490489 I | 492738 | 100 | 84 | 13837 | 35.6 | cholestane | 140330 | 4 | 145943 145943 | 3 H 2 ________________________________________________________________________ weight feces 5.3 mg area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol coprostanon 1 0 0.0 0.0 0 0.00 1 0 0.0 0.0 0 0.00 cholesterol cholestanol lathosterol campesterol 237491 7441 6444 3777 0.98 0.91 1 1.56 232741 6771 6444 5892 86.7 55.6 10481 27.10 2.5 1.6 305 0.78 2.4 1.5 290 0.75 2.2 1.4 265 0.66 stigmasterol b-sitosterol b-sitostanol 982 10254 1.49 1.47 1 1463 15073 0 0.5 0.3 66 5.6 3.6 679 0.0 0.0 0 0.16 1.64 0.00 total | 266389 | | 268385 | 100 | 64 | 12086 | 31.1 | cholestane | 100714 | 4 | 104743 104743 | 3 3 ________________________________________________________________________ weight feces 6.7 mg coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol area 404372 11102 11373 5436 2003 14146 response area corrected factor for response factor 10 10 0.98 396285 0.91 10103 1 11373 1.56 8480 1.49 2984 1.47 20795 10 % 0.0 0.0 88.1 2.2 2.5 1.9 0.7 4.6 0.0 pg sterol 0.0 0.0 72.6 1.9 2.1 1.6 0.5 3.8 0.0 ng sterol/ mg feces 0 0 10838 276 311 232 82 569 0 nmol sterol/ mg feces 0.00 0.00 28.03 0.71 0.80 0.58 0.20 1.37 0.00 total | 448432 | | 450020 | 100 | 82 | 12307 | 31.7 | cholestane 131190 1.04 136438 136438 coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A85 of A172 Appendix to TNO-report of 3M-02 Final version 1:2-4 weight feces 9.1 mg coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol area 473290 9709 12754 6031 2406 17298 response factor 1 1 0.98 0.91 1 1.56 1.49 1.47 1 area corrected for response factor 0 0 463824 8835 12754 9408 3585 25428 0 % 0.0 0.0 88.5 1.7 2.4 1.8 0.7 4.9 0.0 ^ig sterol 0.0 0.0 123.6 2.4 3.4 2.5 1.0 6.8 0.0 ng sterol/ mg feces 0 0 13579 259 373 275 105 744 0 nmol sterol/ mg feces 0.00 0.00 35.12 0.67 0.97 0.69 0.25 1.80 0.00 total I 521488 I | 523835 | 100 | 140 | 15336 | 39.5 | cholestane | 90227 | 1.04 | 1:2-5 weight feces 7.2 mg 93836 93836 coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol area 446804 6124 14209 4560 1811 12767 response factor 1 1 0.98 0.91 1 1.56 1.49 1.47 1 area corrected for response factor 0 0 437868 5573 14209 7114 2698 18767 0 % 0.0 0.0 90.1 1.1 2.9 1.5 0.6 3.9 0.0 ^g sterol 0.0 0.0 114.1 1.5 3.7 1.9 0.7 4.9 0.0 ng sterol/ mg feces 0 0 15846 202 514 257 98 679 0 nmol sterol/ mg feces 0.00 0.00 40.98 0.52 1.33 0.64 0.24 1.64 0.00 total I 486275 I | 486229 | 100 | 127 | 17596 | 45.3 | cholestane | 92255 | 1.04 | 1:2-6 weight feces 6.2 mg 95945 95945 | coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol area 298782 11596 8473 5240 1956 15108 response factor 1 1 0.98 0.91 1 1.56 1.49 1.47 1 area corrected for response factor 0 0 292806 10552 8473 8174 2914 22209 0 % 0.0 0.0 84.8 3.1 2.5 2.4 0.8 6.4 0.0 ^g sterol 0.0 0.0 65.1 2.3 1.9 1.8 0.6 4.9 0.0 ng sterol/ mg feces 0 0 10502 378 304 293 105 797 0 nmol sterol/ mg feces 0.00 0.00 27.16 0.97 0.79 0.73 0.25 1.92 0.00 total I 341155 I | 345129 | 100 | 77 | 12379 | 31.8 | cholestane 108095 1.04 112419 112419 coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A86 of A172 Appendix to TNO-report of 3M-02 Final version 2:2-4 w eight feces 8 .6 mg coprostanol coprostanon cholesterol cholestanol lathosterol c am pestero l stigm asterol b-sitosterol b-sitostanol area 481673 11693 12978 6203 1175 17089 response factor 1 1 0 .9 8 0.91 1 1.56 1.49 1.47 1 area corrected for response factor 0 0 472040 10641 12978 9677 1751 25121 0 % 0 .0 0 .0 88.7 2 .0 2 .4 1.8 0 .3 4 .7 0 .0 pg sterol 0 .0 0 .0 118.2 2 .7 3 .3 2 .4 0 .4 6 .3 0 .0 ng sterol/ mg feces 0 0 13750 310 378 282 51 732 0 nmol sterol/ mg feces 0 .0 0 0 .0 0 35.56 0 .8 0 0 .9 8 0 .7 0 0 .1 2 1.76 0 .0 0 total I 530811 I I 532206 | 100 | 133 | 15502 | 39.9 ~ | cholestane I 95962 | " | 2:2-5 w eight feces 9 .9 mg 998 99800 | coprostanol coprostanon cholesterol cholestanol lathosterol c am pestero l stigm asterol b-sitosterol b-sitostanol area 434117 8812 13243 5232 2068 14440 response area corrected factor for response factor 1 1 0 .9 8 0.91 1 1.56 1.49 1.47 1 0 0 425435 8019 13243 8162 3081 21227 0 % 0 .0 0 .0 88.8 1.7 2 .8 1.7 0 .6 4 .4 0 .0 pg sterol 0 .0 0 .0 152.2 2 .9 4 .7 2 .9 1.1 7.6 0 .0 ng sterol/ mg feces 0 0 15373 290 479 295 111 767 0 nmol sterol/ mg feces 0 .0 0 0 .0 0 39.75 0 .7 5 1.24 0 .7 4 0 .2 7 1.85 0 .0 0 total I 477912 I | 479167 | 100 | 171 | 1731 ^ | 4 4.6 ~ | cholestane | 6 71 9 6 | " | 2:2-6 w eight feces 6 mg 69884 69884 | coprostanol coprostanon cholesterol cholestanol lathosterol c am pestero l stigm asterol b-sitosterol b-sitostanol area 268071 10152 6784 4476 1045 12736 response area corrected factor for response factor 1 1 0 .9 8 0.91 1 1.56 1.49 1.47 1 0 0 262710 9238 6784 6983 1557 18722 0 % 0 .0 0 .0 85.9 3 .0 2.2 2 .3 0 .5 6.1 0 .0 pg sterol 0 .0 0 .0 72.3 2 .5 1.9 1.9 0 .4 5.1 0 .0 ng sterol/ mg feces 0 0 12043 423 311 320 71 858 0 nmol sterol/ mg feces 0 .0 0 0 .0 0 31.14 1.09 0 .8 0 0 .8 0 0 .1 7 2 .0 7 0 .0 0 total I 303264 I | 3 05 9 9 3 | 100 | 84 | 14027 | 36.1 ~ | cholestane [ 8 74 0 0 | 1.04 | 90896 90896 | coprostanol coprostanon cholesterol cholestanol lathosterol c am pestero l stigm asterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A87 of A172 Appendix to TNO-report of 3M-02 Final version 3:2-4 weight feces 5.6 mg coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol area 269271 7132 7058 3976 1401 10601 response factor 1 1 0.98 0.91 1 1.56 1.49 1.47 1 area corrected for response factor 0 0 263886 6490 7058 6203 2087 15583 0 % 0.0 0.0 87.6 2.2 2.3 2.1 0.7 5.2 0.0 pg sterol 0.0 0.0 66.6 1.6 1.8 1.6 0.5 3.9 0.0 ng sterol/ mg feces 0 0 11896 293 318 280 94 702 0 nmol sterol/ mg feces 0.00 0.00 30.76 0.75 0.82 0.70 0.23 1.69 0.00 total I 299439 I | 301307 | 100 | 76 | 13582 | 35.0 | cholestane | 95225 | " | :2-5 weight feces 6.9 mg 99034 99034 | coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol area 398275 7905 11474 4821 1507 11865 response factor 1 1 0.98 0.91 1 1.56 1.49 1.47 1 area corrected for response factor 0 0 390310 7194 11474 7521 2245 17442 0 % 0.0 0.0 89.5 1.6 2.6 1.7 0.5 4.0 0.0 pg sterol 0.0 0.0 79.9 1.5 2.3 1.5 0.5 3.6 0.0 ng sterol/ mg feces 0 0 11581 213 340 223 67 518 0 nmol sterol/ mg feces 0.00 0.00 29.95 0.55 0.88 0.56 0.16 1.25 0.00 total I 435847 I | 436185 | 100 | 89 | 12942 | 33.3 | cholestane | 11741^ | " | :2-6 weight feces 7.2 mg 122111 122111 | coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol area 336997 12422 7963 5484 2009 15075 response factor 1 1 0.98 0.91 1 1.56 1.49 1.47 1 area corrected for response factor 0 0 330257 11304 7963 8555 2993 22160 0 % 0.0 0.0 86.2 2.9 2.1 2.2 0.8 5.8 0.0 pg sterol 0.0 0.0 80.7 2.8 1.9 2.1 0.7 5.4 0.0 ng sterol/ mg feces 0 0 11206 384 270 290 102 752 0 nmol sterol/ mg feces 0.00 0.00 28.98 0.99 0.70 0.72 0.25 1.81 0.00 total I 379950 | | 383233 | 100 | 94 | 13003 | 33.4 | cholestane 98396 1.04 102332 102332 coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A88 of A172 Appendix to TNO-report of 3M-02 Final version | 1:3-7 weight feces 6 mg area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol coprostanon cholesterol 240788 1 1 0.98 0 0 235972 0.0 0.0 0 0.00 0.0 0.0 0 0.00 85.5 67.4 11229 29.04 cholestanol lathosterol 7267 9283 0.91 1 6613 9283 2.4 1.9 315 0.81 3.4 2.7 442 1.14 campesterol 3808 1.56 5940 2.2 1.7 283 0.71 stigmasterol 1488 1.49 2217 0.8 0.6 106 0.26 b-sitosterol b-sitostanol 10778 1.47 1 15844 0 5.7 4.5 754 1.82 0.0 0.0 0 0.00 total | 273412 | | 275869 | 100 | 79 | 13128 | 33.8 | cholestane | 84191 | 1.04 | 87559 87559 | 13-8 weight feces _______________________________________________________________________________ 7 mg area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 283543 0.98 277872 85.5 71.7 10245 26.49 cholestanol 10969 0.91 9982 3.1 2.6 368 0.95 lathosterol 8285 1 8285 2.5 2.1 305 0.79 campesterol 4663 1.56 7274 2.2 1.9 268 0.67 stigmasterol 1774 1.49 2643 0.8 0.7 97 0.24 b-sitosterol 12953 1.47 19041 5.9 4.9 702 1.69 b-sitostanol 1 0 0.0 0.0 0 0.00 total I 322187 I | 325097 | 100 | 84 | 1198^ | 30.8 | cholestane | 93139 | 4 | 96865 ____________________________________96865 1:3-9 weight feces 10.8 mg | area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol coprostanon cholesterol cholestanol 529012 14038 1 1 0.98 0.91 0 0 518432 12775 0.0 0.0 0 0.00 0.0 0.0 0 0.00 89.0 153.4 14205 36.73 2.2 3.8 350 0.90 CM CO lathosterol 11702 1 11702 2.0 3.5 0.83 campesterol stigmasterol b-sitosterol b-sitostanol 6647 1317 18688 1.56 1.49 1.47 1 10369 1962 27471 0 1.8 3.1 284 0.71 0.3 0.6 54 0.13 4.7 8.1 753 1.82 0.0 0.0 0 0.00 total I 581404 I | 582711 | 100 | 172 | 15966 | 41.1 | cholestane 81233 1.04 84482 84482 coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A89 of A172 Appendix to TNO-report of 3M-02 Final version | 2:3-7 weight feces 8 mg area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 330311 0.98 323705 86.2 95.0 11875 30.71 cholestanol 9369 0.91 8526 2.3 2.5 313 0.80 lathosterol 11675 1 11675 3.1 3.4 428 1.11 campesterol 5157 1.56 8045 2.1 2.4 295 0.74 stigmasterol 1936 1.49 2885 0.8 0.8 106 0.26 b-sitosterol 14114 1.47 20748 5.5 6.1 761 1.84 b-sitostanol 1 0 0.0 0.0 0 0.00 total | 372562 1 | 375583 | 100 | 110 | 13778 | 35.4 | cholestane | 81910 | 1.04 | | 2:3-8 weight feces 7.3 mg 85186 85186 | | area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol coprostanon 1 0 0.0 0.0 0 0.00 1 0 0.0 0.0 0 0.00 cholesterol cholestanol 361988 10955 0.98 0.91 354748 9969 87.7 89.9 12322 31.86 2.5 2.5 346 0.89 lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 10492 4873 1595 13274 1 1.56 1.49 1.47 1 10492 7602 2377 19513 0 2.6 2.7 364 1.9 1.9 264 0.6 0.6 83 4.8 4.9 678 0.0 0.0 0 0.94 0.66 0.20 1.63 0.00 total | 403177 1 | 404701 | 100 | 103 | 14057 | 36.2 | cholestane | 94804 | 1.04 | | 2:3-9 weight feces 7.7 mg 98596 98596 | area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol coprostanon cholesterol 409014 1 1 0.98 0 0 400834 0.0 0.0 0 0.0 0.0 0 88.8 109.4 14211 0.00 0.00 36.75 cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 11289 9106 5174 1042 14716 0.91 1 1.56 1.49 1.47 1 10273 9106 8071 1553 21633 0 2.3 2.8 364 2.0 2.5 323 1.8 2.2 286 0.3 0.4 55 4.8 5.9 767 0.0 0.0 0 0.94 0.83 0.71 0.13 1.85 0.00 total | 450341 1 | 451469 | 100 | 123 | 16006 | 41.2 | cholestane 88054 1.04 91576 91576 coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A90 of A172 Appendix to TNO-report of 3M-02 Final version | 3:3-7 weight feces 8.2 mg coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol area 428635 12166 13406 6496 2441 16860 response area corrected factor for response factor 10 10 0.98 420062 0.91 11071 1 13406 1.56 10134 1.49 3637 1.47 24784 10 % 0.0 0.0 87.0 2.3 2.8 2.1 0.8 5.1 0.0 pg sterol 0.0 0.0 95.1 2.5 3.0 2.3 0.8 5.6 0.0 ng sterol/ mg feces 0 0 11598 306 370 280 100 684 0 nmol sterol/ mg feces 0.00 0.00 29.99 0.79 0.96 0.70 0.24 1.65 0.00 total | 480004 1 | 483094 | 100 | 109 | 13338 | 34.3 | cholestane | 10617^ | 1.04 | | 3:3-8 weight feces 7.6 mg 110421 110421 | | coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol area 370433 13556 9317 6050 2043 15825 response area corrected factor for response factor 10 10 0.98 363024 0.91 12336 1 9317 1.56 9438 1.49 3044 1.47 23263 10 % 0.0 0.0 86.3 2.9 2.2 2.2 0.7 5.5 0.0 pg sterol 0.0 0.0 74.7 2.5 1.9 1.9 0.6 4.8 0.0 ng sterol/ mg feces 0 0 9828 334 252 256 82 630 0 nmol sterol/ mg feces 0.00 0.00 25.41 0.86 0.65 0.64 0.20 1.52 0.00 total | 417224 1 | 420422 | 100 | 87 | 1138^ | 29.3 | cholestane | 116833 | " | | 3:3-9 weight feces 6 mg 121506 121506 | | coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol area 327522 9565 7411 4458 1015 11869 response area corrected factor for response factor 10 10 0.98 320972 0.91 8704 1 7411 1.56 6954 1.49 1512 1.47 17447 10 % 0.0 0.0 88.4 2.4 2.0 1.9 0.4 4.8 0.0 pg sterol 0.0 0.0 71.3 1.9 1.6 1.5 0.3 3.9 0.0 ng sterol/ mg feces 0 0 11877 322 274 257 56 646 0 nmol sterol/ mg feces 0.00 0.00 30.71 0.83 0.71 0.64 0.14 1.56 0.00 total | 361840 1 | 363001 | 100 | 81 | 13432 | 34.6 | cholestane | 108272 | 1.04 | 112603 112603 coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A91 of A172 Appendix to TNO-report of 3M-02 Final version 1:4-10 weightfeces 5.9 mg area response areacorrected % pgsterol ngsterol/ nmol sterol/ factor forresponsefactor mgfeces mgfeces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 362101 0.98 354859 88.7 81.6 13829 35.76 cholestanol 9381 0.91 8537 2.1 2.0 333 0.86 lathosterol 7899 1 7899 2.0 1.8 308 0.80 campesterol 4622 1.56 7210 1.8 1.7 281 0.70 stigmasterol 1882 1.49 2804 0.7 0.6 109 0.26 b-sitosterol 12850 1.47 18890 4.7 4.3 736 1.78 b-sitostanol 1 0 0.0 0.0 0 0.00 total I 398735 I | 400199 | 100 | 92 | 15595 | 40.2 | cholestane | 104552 | 4 | 1:4-11 weightfeces 8 mg 108734 | 108734 area response areacorrected % pgsterol ngsterol/ nmol sterol/ factor forresponsefactor mgfeces mgfeces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 489702 0.98 479908 90.0 107.0 13380 34.60 cholestanol 15062 0.91 13706 2.6 3.1 382 0.98 lathosterol 10888 1 10888 2.0 2.4 304 0.78 campesterol 4869 1.56 7596 1.4 1.7 212 0.53 stigmasterol 748 1.49 1115 0.2 0.2 31 0.08 b-sitosterol 13552 1.47 19921 3.7 4.4 555 1.34 b-sitostanol 1 0 0.0 0.0 0 0.00 total I 534821 I | 533134 | 100 | 119 | 14864 | 38.3 | cholestane j 107776 | 1.04 | 1:4-12 weightfeces 6.1 mg 112087 | 112087 area response areacorrected % pgsterol ngsterol/ nmol sterol/ factor forresponsefactor mgfeces mgfeces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 459088 0.98 449906 89.5 96.7 15857 41.01 cholestanol 15039 0.91 13685 2.7 2.9 482 1.24 lathosterol 11182 1 11182 2.2 2.4 394 1.02 campesterol 4797 1.56 7483 1.5 1.6 264 0.66 stigmasterol 686 1.49 1022 0.2 0.2 36 0.09 b-sitosterol 13085 1.47 19235 3.8 4.1 678 1.63 b-sitostanol 1 0 0.0 0.0 0 0.00 total I 503877 I | 502514 | 100 | 108 | 1771^ | 45.6 | cholestane 111810 1.04 116282 116282 coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A92 of A172 Appendix to TNO-report of 3M-02 Final version 2:4-10 weight feces 7.7 mg area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 521217 0.98 510793 90.7 142.2 18473 47.77 cholestanol lathosterol 14915 11055 0.91 1 13573 11055 2.4 3.8 491 2.0 3.1 400 1.26 1.03 campesterol 4779 1.56 7455 1.3 2.1 270 0.67 stigmasterol 743 1.49 1107 0.2 0.3 40 0.10 b-sitosterol 13109 1.47 19270 3.4 5.4 697 1.68 b-sitostanol 1 0 0.0 0.0 0 0.00 total I 565818 1 | 563253 | 100 | 157 | 20370 | 52.5 | cholestane j 86322 | 1.04 | 2:4-11 weight feces 6.4 mg 89775 89775 | area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 497491 0.98 487541 90.8 118.8 18567 48.01 cholestanol 13351 0.91 12149 2.3 3.0 463 1.19 lathosterol 10137 1 10137 1.9 2.5 386 1.00 campesterol 4786 1.56 7466 1.4 1.8 284 0.71 stigmasterol b-sitosterol 727 12456 1.49 1.47 1083 18310 0.2 0.3 41 3.4 4.5 697 0.10 1.68 b-sitostanol 1 0 0.0 0.0 0 0.00 total I 538948 1 | 536687 | 100 | 131 | 20439 | 52.7 | cholestane j 98627 | 1.04 | 2:4-12 weight feces 8.9 mg 102572 102572 | area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 572090 15045 12013 5734 676 15286 1 1 0.98 0.91 1 1.56 1.49 1.47 1 0 0 560648 13691 12013 8945 1007 22470 0 0.0 0.0 0 0.00 0.0 0.0 0 0.00 90.6 171.6 19286 49.87 2.2 4.2 471 1.21 1.9 3.7 413 1.07 1.4 2.7 308 0.77 0.2 0.3 35 0.08 3.6 6.9 773 1.86 0.0 0.0 0 0.00 total I 620844 1 | 618775 | 100 | 189 | 21285 | 54.9 | cholestane j 78519 | 1.04 | 81660 81660 | coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A93 of A172 Appendix to TNO-report of 3M-02 Final version 3:4-10 weight feces 6.8 mg area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 434209 0.98 425525 90.4 89.6 13179 34.08 cholestanol 12431 0.91 11312 2.4 2.4 350 0.90 lathosterol 9196 1 9196 2.0 1.9 285 0.74 campesterol 4448 1.56 6939 1.5 1.5 215 0.54 stigmasterol 651 1.49 970 0.2 0.2 30 0.07 b-sitosterol 11421 1.47 16789 3.6 3.5 520 1.25 b-sitostanol 1 0 0.0 0.0 0 0.00 total I 472356 I | 470731 | 100 | 99 | 14579 | 37.6 | cholestane | TT4T42 | 104 | 3:4-11 weight feces 6.8 mg 118708 118708 | area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol coprostanon cholesterol 690765 1 1 0.98 0 0 676950 0.0 0.0 0 0.00 0.0 0.0 0 0.00 91.4 122.7 18042 46.66 cholestanol lathosterol 15497 14645 0.91 1 14102 14645 1.9 2.6 376 2.0 2.7 390 0.97 1.01 campesterol stigmasterol b-sitosterol b-sitostanol 6317 805 16234 1.56 1.49 1.47 1 9855 1199 23864 0 1.3 1.8 263 0.2 0.2 32 3.2 4.3 636 0.0 0.0 0 0.66 0.08 1.53 0.00 total I 744263 | | 740615 | 100 | 134 | 19739 | 50.9 | cholestane | 132638 | 104 I 3:4-12 weight feces 7.7 mg 137944 137944 area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 657017 16315 13781 6401 812 16291 1 1 0.98 0.91 1 1.56 1.49 1.47 1 0 0 643877 14847 13781 9986 1210 23948 0 0.0 0.0 0 0.00 0.0 0.0 0 0.00 91.0 121.8 15814 40.89 2.1 2.8 365 0.94 1.9 2.6 338 0.88 1.4 1.9 245 0.61 0.2 0.2 30 0.07 3.4 4.5 588 1.42 0.0 0.0 0 0.00 total I 710617 | I 707648 | 100 | 134 | 17380 | 44.8 | cholestane | 12710^ | 1.04 | 132193 132193 | coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A94 of A172 Appendix to TNO-report of 3M-02 Final version | 1:5-13 weight feces 7.8 mg coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol area 482166 15148 13001 5131 1060 14512 response area corrected factor for response factor 10 10 0.98 472523 0.91 13785 1 13001 1.56 8004 1.49 1579 1.47 21333 10 % 0.0 0.0 89.1 2.6 2.5 1.5 0.3 4.0 0.0 pg sterol 0.0 0.0 129.2 3.8 3.6 2.2 0.4 5.8 0.0 ng sterol/ mg feces 0 0 16561 483 456 281 55 748 0 nmol sterol/ mg feces 0.00 0.00 42.83 1.24 1.18 0.70 0.13 1.80 0.00 total | 531018 | I 530225 | 100 | 145 | 18583 | 47.9 | cholestane | 87934 | 104 | | 1:5-14 weight feces 13.4 mg 9T45T 91451 ' area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol cholestanol lathosterol 634279 12599 16167 0.98 0.91 1 621593 11465 16167 89.9 187.2 13972 36.13 1.7 3.5 258 0.66 2.3 4.9 363 0.94 campesterol 6696 1.56 10446 1.5 3.1 235 0.59 stigmasterol b-sitosterol b-sitostanol 2927 18799 1.49 1.47 1 4361 27635 0 0.6 1.3 98 4.0 8.3 621 0.0 0.0 0 0.24 1.50 0.00 total | 691467 | | 691667 | 100 | 208 | 15547 | 40.1 | cholestane | 7981 | 1.04 | 83003 ____________________________________ 83003 1:5-15 weight feces 6.2 mg | area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 255399 0.98 250291 85.5 66.1 10669 27.59 cholestanol 13187 0.91 12000 4.1 3.2 512 1.32 lathosterol 6307 1 6307 2.2 1.7 269 0.70 campesterol 3843 1.56 5995 2.0 1.6 256 0.64 stigmasterol 729 1.49 1086 0.4 0.3 46 0.11 b-sitosterol 11657 1.47 17136 5.9 4.5 730 1.76 b-sitostanol 1 0 0.0 0.0 0 0.00 total | 291122 | | 292815 | 100 | 77 | 12481 | 32.1 | cholestane 90959 1.04 94597 94597 coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A95 of A172 Appendix to TNO-report of 3M-02 Final version | 2:5-13 weightfeces 7.9 mg area response areacorrected % pgsterol ngsterol/ nmol sterol/ factor forresponsefactor mgfeces mgfeces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 455921 0.98 446803 89.0 124.6 15774 40.79 cholestanol 13655 0.91 12426 2.5 3.5 439 1.13 lathosterol 12928 1 12928 2.6 3.6 456 1.18 campesterol 5203 1.56 8117 1.6 2.3 287 0.72 stigmasterol 898 1.49 1338 0.3 0.4 47 0.11 b-sitosterol 13941 1.47 20493 4.1 5.7 723 1.74 b-sitostanol 1 0 0.0 0.0 0 0.00 total | 502546 | | 502105 | 100 | 140 | 17726 | 45.7 | cholestane | 86190 | 104 | | 2:5-14 weightfeces 6.9 mg 89638 89638 | | area response areacorrected % pgsterol ngsterol/ nmol sterol/ factor forresponsefactor mgfeces mgfeces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 302926 0.98 296867 90.2 101.4 14697 38.01 cholestanol 6271 0.91 5707 1.7 1.9 283 0.73 lathosterol 8314 1 8314 2.5 2.8 412 1.06 campesterol 3149 1.56 4912 1.5 1.7 243 0.61 stigmasterol 5 LO 1.49 806 0.2 0.3 40 0.10 b-sitosterol 8475 1.47 12458 3.8 4.3 617 1.49 b-sitostanol 1 0 0.0 0.0 0 0.00 total | 329676 | | 329065 | 100 | 112 | 16291 | 42.0 | cholestane | 70369 | 1.04 | | 2:5-15 weightfeces 4.8 mg 73184 73184 | | area response areacorrected % pgsterol ngsterol/ nmol sterol/ factor forresponsefactor mgfeces mgfeces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 210645 0.98 206432 83.6 52.2 10870 28.11 cholestanol 13493 0.91 12279 5.0 3.1 647 1.66 lathosterol 5461 1 5461 2.2 1.4 288 0.74 campesterol 3832 1.56 5978 2.4 1.5 315 0.79 stigmasterol 733 1.49 1092 0.4 0.3 58 0.14 b-sitosterol 10573 1.47 15542 6.3 3.9 818 1.97 b-sitostanol 1 0 0.0 0.0 0 0.00 total | 244737 | | 246784 | 100 | 62 | 12995 | 33.4 | cholestane 95106 1.04 98910 98910 coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A96 of A172 Appendix to TNO-report of 3M-02 Final version | 3:5-13 weight feces 11.8 mg area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol coprostanon 1 0 0.0 0.0 0 0.00 1 0 0.0 0.0 0 0.00 cholesterol cholestanol 760655 21051 0.98 0.91 745442 19156 88.7 146.6 12425 32.13 2.3 3.8 319 0.82 lathosterol 19855 1 19855 2.4 3.9 331 0.86 campesterol 9056 1.56 14127 1.7 2.8 235 0.59 stigmasterol 3585 1.49 5342 0.6 1.1 89 0.22 b-sitosterol b-sitostanol 24867 1.47 1 36554 0 4.3 7.2 609 1.47 0.0 0.0 0 0.00 total I 839069 | | 840477 | 100 | 165 | 14009 | 36.1 ~ | cholestane | 12221^ | 4 | 127107 | _____________________________________ 127107_____________________________________________ | 3:5-14 ~ weight feces 7.2 mg area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon cholesterol cholestanol 475539 8894 1 0.98 0.91 0 466028 8094 0.0 0.0 0 0.00 90.3 88.3 12257 31.70 1.6 1.5 213 0.55 lathosterol campesterol stigmasterol 11319 4936 2133 1 1.56 1.49 11319 7700 3178 2.2 2.1 298 0.77 1.5 1.5 203 0.51 0.6 0.6 84 0.20 b-sitosterol b-sitostanol 13417 1.47 1 19723 0 3.8 3.7 519 1.25 0.0 0.0 0 0.00 total I 516238 | | 516042 | 100 | 98 | 13573 | 35.0 ~ | cholestane | 126938 | " | | 3:5-15 weight feces 7.1 mg 132016 132016 | ~ area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol coprostanon cholesterol 369324 1 1 0.98 0 0 361938 0.0 0.0 0 0.00 0.0 0.0 0 0.00 85.4 62.2 8763 22.66 cholestanol lathosterol campesterol 21096 8285 6116 0.91 1 1.56 19197 8285 9541 4.5 3.3 465 1.20 2.0 1.4 201 0.52 2.3 1.6 231 0.58 stigmasterol b-sitosterol b-sitostanol 1212 15819 1.49 1.47 1 1806 23254 0 0.4 0.3 44 0.11 5.5 4.0 563 1.36 0.0 0.0 0 0.00 total I 421852 | | 424021 | 100 | 73 | 10267 | 26.4 ~ | cholestane | 139834 | 1.04 | 145427 145427 | coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A97 of A172 Appendix to TNO-report of 3M-02 Final version 1:6-16 weightfeces 5.5 mg area response areacorrected % pgsterol ngsterol/ nmol sterol/ factor forresponsefactor mgfeces mgfeces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 316760 0.98 310425 88.4 75.3 13682 35.38 cholestanol 10679 0.91 9718 2.8 2.4 428 1.10 lathosterol 7883 1 7883 2.2 1.9 347 0.90 campesterol 3863 1.56 6026 1.7 1.5 266 0.66 stigmasterol 573 1.49 854 0.2 0.2 38 0.09 b-sitosterol 10951 1.47 16098 4.6 3.9 710 1.71 b-sitostanol 1 0 0.0 0.0 0 0.00 total I 350709 1 | 351004 | 100 | 85 | 15471 | 39.8 | cholestane | 99T6 | 104 | 1:6-17 weightfeces 5.1 mg 103127 103127 | area response areacorrected % pgsterol ngsterol/ nmol sterol/ factor forresponsefactor mgfeces mgfeces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 283717 0.98 278043 86.7 61.2 12006 31.05 cholestanol 12638 0.91 11501 3.6 2.5 497 1.28 lathosterol 7544 1 7544 2.4 1.7 326 0.84 campesterol 4033 1.56 6291 2.0 1.4 272 0.68 stigmasterol 593 1.49 884 0.3 0.2 38 0.09 b-sitosterol 11162 1.47 16408 5.1 3.6 709 1.71 b-sitostanol 1 0 0.0 0.0 0 0.00 total I 319687 1 | 320670 | 100 | 71 | 13847 | 35.6 | cholestane | 109156 | 104 | 1:6-18 weightfeces 9.3 mg 113522 113522 | area response areacorrected % pgsterol ngsterol/ nmol sterol/ factor forresponsefactor mgfeces mgfeces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 432750 0.98 424095 87.8 121.3 13048 33.74 cholestanol 15694 0.91 14282 3.0 4.1 439 1.13 lathosterol 11216 1 11216 2.3 3.2 345 0.89 campesterol 5531 1.56 8628 1.8 2.5 265 0.66 stigmasterol 828 1.49 1234 0.3 0.4 38 0.09 b-sitosterol 15866 1.47 23323 4.8 6.7 718 1.73 b-sitostanol 1 0 0.0 0.0 0 0.00 total I 481885 1 | 482778 | 100 | 138 | 14853 | 38.2 | cholestane 84015 1.04 87376 87376 coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A98 of A172 Appendix to TNO-report of 3M-02 Final version 2:6-16 weight feces 5.2 mg coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol area 306320 10414 7025 3400 583 9578 response factor 1 1 0.98 0.91 1 1.56 1.49 1.47 1 area corrected for response factor 0 0 300194 9477 7025 5304 869 14080 0 % 0.0 0.0 89.1 2.8 2.1 1.6 0.3 4.2 0.0 |jg sterol 0.0 0.0 71.3 2.2 1.7 1.3 0.2 3.3 0.0 ng sterol/ mg feces 0 0 13705 433 321 242 40 643 0 nmol sterol/ mg feces 0.00 0.00 35.44 1.11 0.83 0.60 0.10 1.55 0.00 total I 337320 1 | 336948 | 100 | 80 | 15383 | 39.6 | cholestane | 10125^ | 1.04 | 2:6-17 weight feces 4.6 mg 105306 105306 coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol area 264813 13978 6351 4076 392 11081 response factor 1 1 0.98 0.91 1 1.56 1.49 1.47 1 area corrected for response factor 0 0 259517 12720 6351 6359 584 16289 0 % 0.0 0.0 86.0 4.2 2.1 2.1 0.2 5.4 0.0 jg sterol 0.0 0.0 58.0 2.8 1.4 1.4 0.1 3.6 0.0 ng sterol/ mg feces 0 0 12612 618 309 309 28 792 0 nmol sterol/ mg feces 0.00 0.00 32.61 1.59 0.80 0.77 0.07 1.91 0.00 total I 300691 1 | 301819 | 100 | 67 | 14667 | 37.8 | cholestane | 107534 | 1.04 | 2:6-18 weight feces 7.1 mg 111835 111835 | coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol area 415098 15248 11257 5140 790 14501 response factor 1 1 0.98 0.91 1 1.56 1.49 1.47 1 area corrected for response factor 0 0 406796 13876 11257 8018 1177 21316 0 % 0.0 0.0 88.0 3.0 2.4 1.7 0.3 4.6 0.0 jg sterol 0.0 0.0 89.1 3.0 2.5 1.8 0.3 4.7 0.0 ng sterol/ mg feces 0 0 12553 428 347 247 36 658 0 nmol sterol/ mg feces 0.00 0.00 32.46 1.10 0.90 0.62 0.09 1.59 0.00 total I 462034 1 | 462441 | 100 | 101 | 14270 | 36.8 | cholestane | 109718 | 1.04 | 114107 114107 | coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A99 of A172 Appendix to TNO-report of 3M-02 Final version 3:6-16 weightfeces 9.4 mg area response areacorrected % pgsterol ngsterol/ nmol sterol/ factor forresponsefactor mgfeces mgfeces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 528030 0.98 517469 90.2 120.9 12861 33.26 cholestanol 15892 0.91 14462 2.5 3.4 359 0.92 lathosterol 10925 1 10925 1.9 2.6 272 0.70 campesterol 5503 1.56 8585 1.5 2.0 213 0.53 stigmasterol ID 1.49 1134 0.2 0.3 28 0.07 b-sitosterol 14410 1.47 21183 3.7 4.9 526 1.27 b-sitostanol 1 0 0.0 0.0 0 0.00 total I 575521 1 | 573757 | 100 | 134 | 14260 | 36.8 | cholestane | 102895 | " | 3:6-17 weightfeces 5.2 mg 107011 107011 | area response areacorrected % pgsterol ngsterol/ nmol sterol/ factor forresponsefactor mgfeces mgfeces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 325132 0.98 318629 87.3 55.5 10671 27.59 cholestanol 15757 0.91 14339 3.9 2.5 480 1.24 lathosterol 7236 1 7236 2.0 1.3 242 0.63 campesterol 4495 1.56 7012 1.9 1.2 235 0.59 stigmasterol 611 1.49 910 0.2 0.2 30 0.07 b-sitosterol 11479 1.47 16874 4.6 2.9 565 1.36 b-sitostanol 1 0 0.0 0.0 0 0.00 total I 36471^1 | 365001 | 100 | 64 | 12224 | 31.5 | cholestane | 138038 | 4 | 3:6-18 weightfeces 6.9 mg 143560 | 143560 area response areacorrected % pgsterol ngsterol/ nmol sterol/ factor forresponsefactor mgfeces mgfeces coprostanol 1 0 0.0 0.0 0 0.00 coprostanon 1 0 0.0 0.0 0 0.00 cholesterol 716301 0.98 701975 88.7 96.4 13976 36.14 cholestanol 24577 0.91 22365 2.8 3.1 445 1.15 lathosterol 18733 1 18733 2.4 2.6 373 0.96 campesterol 8508 1.56 13272 1.7 1.8 264 0.66 stigmasterol 1102 1.49 1642 0.2 0.2 33 0.08 b-sitosterol 22755 1.47 33450 4.2 4.6 666 1.61 b-sitostanol 1 0 0.0 0.0 0 0.00 total I 791976 1 | 791437 | 100 | 109 | 15758 | 40.6 | cholestane 174978 1.04 181977 181977 coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A100 of A172 Appendix to TNO-report of 3M-02 Final version | 1:7-19 weight feces 7 .5 mg coprostanol coprostanon cholesterol cholestanol lathosterol cam pestero l stig m a s te ro l b-sitosterol b-sitostanol area 449806 25289 7667 6477 917 18151 response factor 1 1 0 .9 8 0.91 1 1.56 1.49 1.47 1 area corrected for response factor 0 0 440810 23013 7667 10104 1366 26682 0 % 0.0 0.0 86.5 4.5 1.5 2.0 0.3 5.2 0.0 pg sterol 0 .0 0 .0 98.4 5.1 1.7 2.3 0.3 6 .0 0.0 ng sterol/ mg feces 0 0 13115 685 228 301 41 794 0 nmol sterol/ mg feces 0 .0 0 0 .0 0 33.92 1.76 0 .5 9 0 .7 5 0 .1 0 1.91 0 .0 0 total I 508307 | | 509642 | 100 | 114 | 15163 | 39.0 ~ | cholestane | 107726 | 1 0 4 | | 1 :7-20 weight feces 10.8 mg 112035 112035 | ' coprostanol coprostanon cholesterol cholestanol lathosterol c am pestero l stig m a s te ro l b-sitosterol b-sitostanol area 497481 30777 9362 7714 1041 21441 response factor 1 1 0 .9 8 0.91 1 1.56 1.49 1.47 1 area corrected for response factor 0 0 487531 28007 9362 12034 1551 31518 0 % 0.0 0.0 85.5 4.9 1.6 2.1 0.3 5.5 0.0 pg sterol 0 .0 0 .0 119.2 6 .9 2 .3 2 .9 0 .4 7.7 0.0 ng sterol/ mg feces 0 0 11041 634 212 273 35 714 0 nmol sterol/ mg feces 0 .0 0 0 .0 0 28.55 1.63 0 .5 5 0 .6 8 0 .0 9 1.72 0 .0 0 total I 567816 | | 570004 | 100 | 139 | 12909 | 33.2 ~ | cholestane | 98281 | " | | 1:7-21 weight feces 8 .5 mg 102212 102212 | 1 coprostanol coprostanon cholesterol cholestanol lathosterol c am pestero l stig m a s te ro l b-sitosterol b-sitostanol area 328489 18232 5881 5028 654 13624 response area corrected factor for response factor 1 1 0 .9 8 0.91 1 1.56 1.49 1.47 1 0 0 321919 16591 5881 7844 974 20027 0 % 0.0 0.0 86.3 4.4 1.6 2.1 0.3 5.4 0.0 pg sterol 0 .0 0 .0 100.2 5.2 1.8 2 .4 0 .3 6.2 0.0 ng sterol/ mg feces 0 0 11792 608 215 287 36 734 0 nmol sterol/ mg feces 0 .0 0 0 .0 0 30.49 1.56 0 .5 6 0 .7 2 0 .0 9 1.77 0 .0 0 total I 371908 | | 373237 | 100 | 116 | 13671 | 35.2 ~ | cholestane 77207 1.04 80295 80295 coprostanol coprostanon cholesterol cholestanol lathosterol c am pestero l stig m a s te ro l b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A101 of A172 Appendix to TNO-report of 3M-02 Final version weight feces 7.3 mg coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol area 393028 19805 6961 5235 2749 13255 response area corrected factor for response factor 10 10 0.98 385167 0.91 18023 1 6961 1.56 8167 1.49 4096 1.47 19485 10 % 0.0 0.0 87.2 4.1 1.6 1.8 0.9 4.4 0.0 pg sterol 0.0 0.0 87.9 4.1 1.6 1.9 0.9 4.4 0.0 ng sterol/ mg feces 0 0 12046 564 218 255 128 609 0 nmol sterol/ mg feces 0.00 0.00 31.15 1.45 0.56 0.64 0.31 1.47 0.00 total | 441033 J | 441898 | 100 | 101 | 13820 | 35.6 | cholestane I 105292 | 1.04 | | 2:7-20 weight feces 7 mg 109504 109504 | | coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol area 363884 22163 6943 5485 752 14149 response area corrected factor for response factor 10 10 0.98 356606 0.91 20168 1 6943 1.56 8557 1.49 1120 1.47 20799 10 % 0.0 0.0 86.1 4.9 1.7 2.1 0.3 5.0 0.0 pg sterol 0.0 0.0 91.7 5.2 1.8 2.2 0.3 5.4 0.0 ng sterol/ mg feces 0 0 13105 741 255 314 41 764 0 nmol sterol/ mg feces 0.00 0.00 33.89 1.91 0.66 0.78 0.10 1.84 0.00 total I 413376 J | 414194 | 100 | 107 | 15222 | 39.2 | cholestane | 93444 | 1.04 | | 2:7-21 weight feces 6.9 mg 97182 97182 | | area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol coprostanon 1 0 0.0 0.0 0 0.00 1 0 0.0 0.0 0 0.00 cholesterol cholestanol lathosterol 399924 19224 7234 0.98 0.91 1 391926 17494 7234 87.3 88.6 12845 33.22 3.9 4.0 573 1.48 1.6 1.6 237 0.61 campesterol stigmasterol 5395 2024 1.56 1.49 8416 3016 1.9 1.9 276 0.7 0.7 99 0.69 0.24 cO)o b-sitosterol b-sitostanol 14143 1.47 1 20790 0 4.6 4.7 1.64 0.0 0.0 0 0.00 total | 447944 1 | 448876 | 100 | 102 | 1471^ | 37.9 | cholestane j 106300 | 1.04 | 110552 110552 coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A102 of A172 Appendix to TNO-report of 3M-02 Final version | 3:7-19 weight feces 10 mg area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol coprostanon 1 0 0.0 0.0 0 0.00 1 0 0.0 0.0 0 0.00 cholesterol cholestanol lathosterol 582689 23901 10390 0.98 0.91 1 571035 21750 10390 88.5 114.6 11457 29.63 3.4 4.4 436 1.12 1.6 2.1 208 0.54 campesterol 7529 1.56 11745 1.8 2.4 236 0.59 stigmasterol 942 1.49 1404 0.2 0.3 28 0.07 b-sitosterol b-sitostanol 19466 1.47 1 28615 0 4.4 5.7 574 0.0 0.0 0 1.38 0.00 total | 644917 | | 644939 | 100 | 129 | 12940 | 33.3 | cholestane | 11981^ | 1.04 | | 3:7-20 weight feces 4.9 mg 124603 124603 | | coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol area 282329 16221 5485 3642 437 9568 response area corrected factor for response factor 10 10 0.98 276682 0.91 14761 1 5485 1.56 5682 1.49 651 1.47 14065 10 % 0.0 0.0 87.2 4.7 1.7 1.8 0.2 4.4 0.0 pg sterol 0.0 0.0 56.9 3.0 1.1 1.2 0.1 2.9 0.0 ng sterol/ mg feces 0 0 11609 619 230 238 27 590 0 nmol sterol/ mg feces 0.00 0.00 30.02 1.59 0.60 0.59 0.07 1.42 0.00 total | 317682 l | 317326 | 100 | 65 | 13314 | 34.3 | cholestane | 116924 | 14 | | 3:7-21 weight feces 9.5 mg 121601 121601 | | area response area corrected % pg sterol ng sterol/ nmol sterol/ factor for response factor mg feces mg feces coprostanol coprostanon 1 0 0.0 0.0 0 0.00 1 0 0.0 0.0 0 0.00 cholesterol 486322 0.98 476596 88.6 110.7 11653 30.13 cholestanol lathosterol 21163 7823 0.91 1 19258 7823 3.6 4.5 471 1.5 1.8 191 1.21 0.49 campesterol stigmasterol 6293 622 1.56 1.49 9817 927 1.8 2.3 240 0.2 0.2 23 0.60 0.05 b-sitosterol b-sitostanol 16081 1.47 1 23639 0 4.4 5.5 578 0.0 0.0 0 1.39 0.00 total | 538304 | | 538060 | 100 | 125 | 1315^ | 33.9 | cholestane 103492 1.04 107632 107632 coprostanol coprostanon cholesterol cholestanol lathosterol campesterol stigmasterol b-sitosterol b-sitostanol 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 388.7 386.7 386.7 388.7 386.7 400.7 412.7 414.7 416.7 04-12-2006 Page A103 of A172 Appendix to TNO-report of 3M-02____________ Final version__________________________04-12-2006 Page A104 of A172 group 1 1 1 1 i 1 1 1 1 AVERAGE SD 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 4 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 AVERAGE SD cage# 1,2 3 ,4 5 1,2 3 ,4 5 1,2 3 ,4 5 GC sam ple# 1:1-1 1 :1 -2 1 :1 -3 2:1-1 2 :1 -2 2 :1 -3 3:1-1 3 :1 -2 3 :1 -3 coprostanol 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 neutral sterols (um ol/g feces) coprostanon cholesterol cholestanol 0 .0 0 2 5 .1 3 0 .7 5 0 .0 0 3 0 .5 2 0 .8 4 0 .0 0 2 6 .7 6 0 .7 1 0 .0 0 3 2 .4 1 1 .0 7 0 .0 0 0 .0 0 3 2 .5 6 3 4 .1 7 0 .8 9 0 .9 3 0 .0 0 3 1 .3 4 0 .8 8 0 .0 0 2 7 .1 0 0 .7 8 0 .0 0 2 8 .0 3 0 .7 1 lath osterol 0.91 0 .8 9 0 .9 4 1 .0 8 0 .8 5 1 .1 4 0 .8 6 0 .7 5 0 .8 0 neutral sterols total (um ol/g feces) 2 6 .7 9 3 2 .2 6 2 8 .4 0 3 4 .5 6 3 4 .3 0 3 6 .2 5 3 3 .0 8 2 8 .6 4 2 9 .5 4 total feces (g) 3 .0 7 5 2.4 8 9 7 2.2 9 4 6 4 .6 9 2 3.7 7 8 9 3.4 1 0 6 3.5 7 5 4 2 .8 7 8 1 2.7 5 8 9 average w eight (g) 1 2 3 .6 8 7 .2 5 8 8 .5 5 1 2 2 .4 5 8 6 .5 5 8 8 .2 1 2 1 .6 5 8 6 .5 5 8 8 .0 5 days 2 2 2 3 3 3 2 2 2 6 7 ,8 9 ,1 0 6 7 ,8 9 ,1 0 6 7 ,8 9 ,1 0 1 :2 -4 1 :2 -5 1 :2 -6 2 :2 -4 2 :2 -5 2 :2 -6 3 :2 -4 3 :2 -5 3 :2 -6 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 3 5 .1 2 4 0 .9 8 2 7 .1 6 3 5 .5 6 3 9 .7 5 3 1 .1 4 3 0 .7 6 2 9 .9 5 2 8 .9 8 0 .6 7 0 .5 2 0 .9 7 0 .8 0 0 .7 5 1 .0 9 0 .7 5 0 .5 5 0 .9 9 0 .9 7 1 .3 3 0 .7 9 0 .9 8 1 .2 4 0 .8 0 0 .8 2 0 .8 8 0 .7 0 3 6 .7 5 4 2 .8 3 2 8 .9 2 3 7 .3 3 4 1 .7 4 3 3 .0 4 3 2 .3 4 3 1 .3 8 3 0 .6 6 2.7 6 1 9 4 .0 5 8 1 2.0 9 3 5 4 .0 7 5 6 .3 7 1 3.4 0 7 4 2.9 2 7 9 4.3 9 8 5 2.4 5 7 5 9 4 .5 5 1 2 6 .6 8 2 .2 9 4 .2 5 1 2 6 .4 5 82.1 94 1 2 6 .6 8 1 .8 5 2 2 2 3 3 3 2 2 2 1 1 ,1 2 ,1 3 15 1 4 ,1 6 ,1 7 1 1 ,1 2 ,1 3 15 1 4 ,1 6 ,1 7 1 1 ,1 2 ,1 3 15 1 4 ,1 6 ,1 7 1 :3 -7 1 :3 -8 1 :3 -9 2 :3 -7 2 :3 -8 2 :3 -9 3 :3 -7 3 :3 -8 3 :3 -9 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 2 9 .0 4 2 6 .4 9 3 6 .7 3 3 0 .7 1 3 1 .8 6 3 6 .7 5 2 9 .9 9 2 5 .4 1 3 0 .7 1 0 .8 1 0 .9 5 0 .9 0 0 .8 0 0 .8 9 0 .9 4 0 .7 9 0 .8 6 0 .8 3 1 .1 4 0 .7 9 0 .8 3 1.11 0 .9 4 0 .8 3 0 .9 6 0 .6 5 0.71 3 0 .9 9 2 8 .2 3 3 8 .4 6 3 2 .6 2 3 3 .7 0 3 8 .5 2 3 1 .7 4 2 6 .9 3 3 2 .2 5 3.4 5 9 7 2.2 9 9 4 2.3 4 5 4 5.8 1 4 7 3.7 7 1 8 3.7 7 2 7 4 .0 2 5 2.5 2 6 5 2.6 9 0 5 118 8 3 .5 5 8 2 .8 1 1 8 .7 5 8 3 .5 8 3 .0 5 1 1 9 .6 8 4 .2 8 3 .4 5 2 2 2 3 3 3 2 2 2 18 19 2 0 ,2 1 18 19 2 0 ,2 1 18 19 2 0 ,2 1 1 :4 -1 0 1 :4 -1 1 1 :4 -1 2 2 :4 -1 0 2:4-11 2 :4 -1 2 3 :4 -1 0 3:4-11 3 :4 -1 2 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 3 5 .7 6 3 4 .6 0 4 1 .0 1 4 7 .7 7 4 8 .0 1 4 9 .8 7 3 4 .0 8 4 6 .6 6 4 0 .8 9 0 .8 6 0 .9 8 1 .2 4 1 .2 6 1 .1 9 1.21 0 .9 0 0 .9 7 0 .9 4 0 .8 0 0 .7 8 1 .0 2 1 .0 3 1 .0 0 1 .0 7 0 .7 4 1.01 0 .8 8 3 7 .4 1 3 6 .3 7 4 3 .2 7 5 0 .0 7 5 0 .2 0 5 2 .1 5 3 5 .7 2 4 8 .6 3 4 2 .7 1 1 .6 8 9 3.1 4 3 2 3.2 5 4 5 2.7 1 3 3 4.6 4 0 7 5.2 0 7 5 2 .0 4 1 3.4 4 6 4 3.9 5 4 9 5 9 .5 1 1 6 .4 1 1 2 .2 5 8 .8 5 1 1 6 .5 5 1 1 1 .8 5 5 8 .7 1 1 7 .4 5 1 1 2 .9 2 2 2 3 3 3 2 2 2 22 2 4 ,2 5 2 3 ,2 6 ,2 7 22 2 4 ,2 5 2 3 ,2 6 ,2 7 22 2 4 ,2 5 2 3 ,2 6 ,2 7 1 :5 -1 3 1 :5 -1 4 1 :5 -1 5 2 :5 -1 3 2 :5 -1 4 2 :5 -1 5 3 :5 -1 3 3 :5 -1 4 3 :5 -1 5 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 4 2 .8 3 3 6 .1 3 2 7 .5 9 4 0 .7 9 3 8 .0 1 2 8 .1 1 3 2 .1 3 3 1 .7 0 2 2 .6 6 1 .2 4 0 .6 6 1 .3 2 1 .1 3 0 .7 3 1 .6 6 0 .8 2 0 .5 5 1 .2 0 1 .1 8 0 .9 4 0 .7 0 1 .1 8 1 .0 6 0 .7 4 0 .8 6 0 .7 7 0 .5 2 4 5 .2 5 3 7 .7 3 2 9 .6 0 4 3 .1 0 3 9 .8 0 3 0 .5 2 3 3 .8 1 3 3 .0 1 2 4 .3 8 3 .1 9 5 2.9 4 0 8 2.6 3 9 9 4.9 7 1 2 4.4 8 3 3 3 .7 6 7 3.6 1 1 3 3.3 5 2 2 2.7 0 3 4 1 1 0 .7 8 8 .3 5 8 4 .6 1 1 1 .6 8 8 .5 8 5 .5 5 1 1 2 .8 5 8 8 .9 8 5 .5 2 2 2 3 3 3 2 2 2 2 8 ,2 9 31 3 0 ,3 2 2 8 ,2 9 31 3 0 ,3 2 2 8 ,2 9 31 3 0 ,3 2 1 :6 -1 6 1 :6 -1 7 1 :6 -1 8 2 :6 -1 6 2 :6 -1 7 2 :6 -1 8 3 :6 -1 6 3 :6 -1 7 3 :6 -1 8 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 3 5 .3 8 3 1 .0 5 3 3 .7 4 3 5 .4 4 3 2 .6 1 3 2 .4 6 3 3 .2 6 2 7 .5 9 3 6 .1 4 1 .1 0 1 .2 8 1 .1 3 1.11 1 .5 9 1 .1 0 0 .9 2 1 .2 4 1 .1 5 0 .9 0 0 .8 4 0 .8 9 0 .8 3 0 .8 0 0 .9 0 0 .7 0 0 .6 3 0 .9 6 3 7 .3 8 3 3 .1 7 3 5 .7 6 3 7 .3 8 3 5 .0 0 3 4 .4 6 3 4 .8 8 2 9 .4 6 3 8 .2 5 2.5 0 3 6 2.7 0 8 3 2.3 5 5 4 3.9 6 8 4 3.9 6 7 8 3.5 6 6 6 2.9 0 7 6 3.2 4 4 9 2.7 6 4 3 87.1 1 1 2 .8 8 5 .4 8 7 .1 5 1 1 2 .4 5 8 4 .5 5 8 7 .6 5 1 1 1 .9 5 8 4 .6 5 2 2 2 3 3 3 2 2 2 3 3 ,3 4 ,3 5 3 6 ,3 7 3 8 ,3 9 3 3 ,3 4 ,3 5 3 6 ,3 7 3 8 ,3 9 3 3 ,3 4 ,3 5 3 6 ,3 7 3 8 ,3 9 1 :7 -1 9 1 :7 -2 0 1 :7 -2 1 2 :7 -1 9 2 :7 -2 0 2:7-21 3 :7 -1 9 3 :7 -2 0 3:7-21 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 3 3 .9 2 2 8 .5 5 3 0 .4 9 3 1 .1 5 3 3 .8 9 3 3 .2 2 2 9 .6 3 3 0 .0 2 3 0 .1 3 1 .7 6 1 .6 3 1 .5 6 1 .4 5 1.91 1 .4 8 1 .1 2 1 .5 9 1.21 0 .5 9 0 .5 5 0 .5 6 0 .5 6 0 .6 6 0.61 0 .5 4 0 .6 0 0 .4 9 3 6 .2 7 3 0 .7 3 3 2 .6 1 3 3 .1 6 3 6 .4 6 3 5 .3 0 3 1 .2 9 3 2 .2 1 3 1 .8 4 1 .9 6 9 7 2.0 7 9 8 2.6 7 0 5 3.4 4 7 7 3.2 6 4 6 4.3 0 5 9 2.5 1 1 7 2.4 3 6 9 3.4 1 0 7 8 1 .3 5 8 2 .2 5 1 0 1 .0 5 8 2 .3 5 8 2 .7 5 1 0 1 .9 5 8 3 .5 8 3 .3 5 1 0 3 .2 2 2 2 3 3 3 2 2 2 total neutrol sterols excretion (um ol/100 gr m ouse/day) 3 3 .3 3 4 6 .0 2 3 6 .8 0 4 4 .1 4 4 9 .9 2 4 6 .7 3 4 8 .6 2 4 7 .6 2 4 6 .2 8 4 4 .3 8 5 .6 0 5 3 .6 7 6 8 .6 4 3 6 .8 3 5 3 .8 0 7 0 .1 0 4 5 .7 0 5 0 .3 6 5 4 .5 1 4 6 .0 3 5 3 .2 9 1 0 .6 6 4 5 .4 3 3 8 .8 5 5 4 .4 8 5 3 .2 4 5 0 .7 4 5 8 .3 3 5 3 .4 0 4 0 .4 0 5 1 .9 9 4 9 .6 5 6 .6 4 5 3 .1 0 4 9 .1 0 6 2 .7 5 7 6 .9 5 6 6 .6 3 8 0 .9 4 6 2 .1 0 7 1 .3 5 7 4 .8 0 6 6 .4 1 1 0 .7 6 6 5 .3 0 6 2 .8 0 4 6 .1 8 6 4 .0 0 6 7 .2 0 4 4 .7 9 5 4 .1 0 6 2 .2 5 3 8 .5 4 5 6 .1 3 1 0 .5 6 5 3 .7 3 3 9 .8 2 4 9 .3 2 5 6 .7 4 4 1 .1 7 4 8 .4 6 5 7 .8 6 4 2 .6 9 6 2 .4 6 5 0 .2 5 8.01 4 3 .9 1 3 8 .8 6 4 3 .1 0 4 6 .2 8 4 7 .9 4 4 9 .7 0 4 7 .0 6 4 7 .0 8 5 2 .6 1 4 6 .2 8 3 .9 8 coprostanol 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 % o f neutral sterols coprostanon cholesterol cholestanol 0 .0 0 9 3 .7 9 2 .8 1 0 .0 0 0 .0 0 9 4 .6 2 9 4 .2 1 2 .6 0 2 .4 9 0 .0 0 9 3 .7 7 3 .1 0 0 .0 0 0 .0 0 9 4 .9 3 9 4 .2 7 2 .5 9 2 .5 7 0 .0 0 9 4 .7 4 2 .6 7 0 .0 0 9 4 .6 4 2 .7 4 0 .0 0 9 4 .8 7 2 .4 1 0 .0 0 0 .0 0 9 4 .4 3 0 .4 4 2 .6 7 0 .2 0 0 .0 0 9 5 .5 6 1.81 0 .0 0 0 .0 0 9 5 .6 8 9 3 .9 2 1.21 3 .3 7 0 .0 0 9 5 .2 5 2 .1 4 0 .0 0 0 .0 0 9 5 .2 5 9 4 .2 7 1 .7 9 3 .3 0 0 .0 0 9 5 .1 3 2 .3 3 0 .0 0 0 .0 0 9 5 .4 4 9 4 .5 0 1 .7 5 3 .2 2 0 .0 0 9 5 .0 0 2 .3 2 0 .0 0 0 .6 2 0 .7 9 0 .0 0 9 3 .7 0 2 .6 1 0 .0 0 0 .0 0 9 3 .8 5 9 5 .5 0 3 .3 5 2 .3 4 0 .0 0 9 4 .1 4 2 .4 7 0 .0 0 0 .0 0 9 4 .5 6 9 5 .4 0 2 .6 4 2 .4 3 0 .0 0 9 4 .5 1 2 .4 8 0 .0 0 0 .0 0 9 4 .3 9 9 5 .2 3 3 .1 9 2 .5 7 0 .0 0 0 .0 0 9 4 .5 9 0 .6 6 2 .6 8 0 .3 5 0 .0 0 0 .0 0 9 5 .5 8 9 5 .1 4 2 .2 9 2 .7 0 0 .0 0 9 4 .7 8 2 .8 7 0 .0 0 9 5 .4 1 2 .5 2 0 .0 0 0 .0 0 9 5 .6 4 9 5 .6 3 2 .3 7 2 .3 2 0 .0 0 9 5 .4 1 2 .5 2 0 .0 0 0 .0 0 9 5 .9 4 9 5 .7 5 1 .9 9 2 .2 0 0 .0 0 9 5 .4 8 2 .4 2 0 .0 0 0 .3 5 0 .2 7 0 .0 0 0 .0 0 0 .0 0 9 4 .6 5 9 5 .7 5 9 3 .2 1 2 .7 5 1 .7 6 4 .4 5 0 .0 0 0 .0 0 9 4 .6 4 9 5 .5 0 2 .6 2 1 .8 3 0 .0 0 9 2 .1 1 5 .4 5 0 .0 0 9 5 .0 4 2 .4 3 0 .0 0 0 .0 0 9 6 .0 1 9 2 .9 7 1 .6 6 4 .9 1 0 .0 0 9 4 .4 3 3 .0 9 0 .0 0 1 .3 6 1 .4 5 0 .0 0 0 .0 0 9 4 .6 5 9 3 .6 1 2 .9 5 3 .8 5 0 .0 0 9 4 .3 4 3 .1 6 0 .0 0 0 .0 0 0 .0 0 9 4 .8 0 9 3 .1 8 9 4 .2 0 2 .9 8 4 .5 4 3 .2 0 0 .0 0 0 .0 0 9 5 .3 4 9 3 .6 8 2 .6 5 4 .1 9 0 .0 0 9 4 .4 8 2 .9 9 0 .0 0 0 .0 0 9 4 .2 5 0 .6 7 3 .3 9 0 .6 5 0 .0 0 9 3 .5 2 4 .8 6 0 .0 0 9 2 .9 1 5 .3 1 0 .0 0 9 3 .5 0 4 .7 9 0 .0 0 0 .0 0 0 .0 0 9 3 .9 3 9 2 .9 6 9 4 .0 9 4 .3 7 5 .2 3 4 .1 8 0 .0 0 0 .0 0 9 4 .6 9 9 3 .2 1 3 .5 9 4 .9 5 0 .0 0 9 4 .6 4 3 .8 0 0 .0 0 0 .0 0 9 3 .7 1 0 .6 7 4 .5 6 0 .6 1 1 lath osterol 3 .4 0 2 .7 7 3 .3 0 3 .1 3 2 .4 8 3 .1 6 2 .5 9 2 .6 2 2 .7 2 2.91 0 .3 4 2 .6 3 3 .1 0 2 .7 2 2 .6 2 2 .9 6 2 .4 3 2 .5 4 2.81 2 .2 8 2 .6 8 0 .2 6 3 .6 9 2 .8 0 2 .1 6 3 .4 0 2 .8 0 2 .1 7 3 .0 2 2 .4 2 2 .2 0 2 .7 4 0 .5 6 2 .1 3 2 .1 6 2 .3 6 2 .0 7 1 .9 9 2 .0 5 2 .0 6 2 .0 8 2 .0 5 2 .1 0 0.11 2 .6 0 2 .4 9 2 .3 5 2 .7 4 2 .6 7 2 .4 4 2 .5 3 2 .3 3 2 .1 3 2 .4 8 0 .1 9 2 .4 0 2 .5 4 2 .5 0 2 .2 2 2 .2 8 2.61 2.01 2 .1 3 2 .5 2 2 .3 6 0.21 1 .6 3 1 .7 8 1.71 1 .7 0 1.81 1 .7 4 1 .7 2 1 .8 5 1 .5 5 1 .7 2 0 .0 9 Appendix to TNO-report of 3M-02____________ Final version__________________________04-12-2006 Page A105 of A172 group i i 1 1 1 1 1 1 1 AVERAGE SD 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 4 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 AVERAGE SD cage# 1,2 3 ,4 5 1,2 3 ,4 5 1,2 3 ,4 5 GC sam ple# 1:1-1 1 :1 -2 1 :1 -3 2:1-1 2 :1 -2 2 :1 -3 3:1-1 3 :1 -2 3 :1 -3 neutral sterols (pm ol/g feces) ca m p e ste ro l stig m a ste ro l b -sito ste ro l b -sito sta n o l 0 .6 3 0.21 1 .7 0 0 .0 0 0 .7 2 0 .2 5 1 .8 4 0 .0 0 0 .6 0 0 .2 0 1.51 0 .0 0 0 .7 8 0 .1 8 1 .9 3 0 .0 0 0 .7 3 0 .2 5 1 .7 9 0 .0 0 0 .7 5 0 .2 4 1 .9 4 0 .0 0 0 .6 8 0.21 1 .6 4 0 .0 0 0 .6 6 0 .1 6 1 .6 4 0 .0 0 0 .5 8 0 .2 0 1 .3 7 0 .0 0 neutral sterols total (pm ol/g feces) 2 .5 4 2 .8 1 2 .3 1 2 .9 0 2 .7 7 2 .9 3 2 .5 4 2 .4 6 2 .1 5 total feces (g) 3 .0 7 5 2 .4 8 9 7 2 .2 9 4 6 4 .6 9 2 3 .7 7 8 9 3 .4 1 0 6 3 .5 7 5 4 2 .8 7 8 1 2 .7 5 8 9 average w eight (g) 1 2 3 .6 8 7 .2 5 8 8 .5 5 1 2 2 .4 5 8 6 .5 5 8 8 .2 1 2 1 .6 5 8 6 .5 5 8 8 .0 5 days 2 2 2 3 3 3 2 2 2 6 7 ,8 9 ,1 0 6 7 ,8 9 ,1 0 6 7 ,8 9 ,1 0 1 :2 -4 1 :2 -5 1 :2 -6 2 :2 -4 2 :2 -5 2 :2 -6 3 :2 -4 3 :2 -5 3 :2 -6 0 .6 9 0 .6 4 0 .7 3 0 .7 0 0 .7 4 0 .8 0 0 .7 0 0 .5 6 0 .7 2 0 .2 5 0 .2 4 0 .2 5 0 .1 2 0 .2 7 0 .1 7 0 .2 3 0 .1 6 0 .2 5 1 .8 0 1 .6 4 1 .9 2 1 .7 6 1 .8 5 2 .0 7 1 .6 9 1 .2 5 1.81 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 2 .7 4 2 .5 2 2 .9 1 2 .5 9 2 .8 6 3 .0 4 2 .6 2 1 .9 7 2 .7 8 2 .7 6 1 9 4 .0 5 8 1 2 .0 9 3 5 4 .0 7 5 6 .3 7 1 3 .4 0 7 4 2 .9 2 7 9 4 .3 9 8 5 2 .4 5 7 5 9 4 .5 5 1 2 6 .6 8 2 .2 9 4 .2 5 1 2 6 .4 5 82.1 94 1 2 6 .6 8 1 .8 5 2 2 2 3 3 3 2 2 2 1 1 ,1 2 ,1 3 15 1 4 ,1 6 ,1 7 1 1 ,1 2 ,1 3 15 1 4 ,1 6 ,1 7 1 1 ,1 2 ,1 3 15 1 4 ,1 6 ,1 7 1 :3 -7 1 :3 -8 1 :3 -9 2 :3 -7 2 :3 -8 2 :3 -9 3 :3 -7 3 :3 -8 3 :3 -9 0 .7 1 0 .6 7 0 .7 1 0 .7 4 0 .6 6 0 .7 1 0 .7 0 0 .6 4 0 .6 4 0 .2 6 0 .2 4 0 .1 3 0 .2 6 0 .2 0 0 .1 3 0 .2 4 0 .2 0 0 .1 4 1 .8 2 1 .6 9 1 .8 2 1 .8 4 1 .6 3 1 .8 5 1 .6 5 1 .5 2 1 .5 6 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 2 .7 8 2 .6 0 2 .6 5 2 .8 3 2 .4 9 2 .7 0 2 .5 9 2 .3 6 2 .3 3 3 .4 5 9 7 2 .2 9 9 4 2 .3 4 5 4 5 .8 1 4 7 3 .7 7 1 8 3 .7 7 2 7 4 .0 2 5 2 .5 2 6 5 2 .6 9 0 5 118 8 3 .5 5 8 2 .8 1 1 8 .7 5 8 3 .5 8 3 .0 5 1 1 9 .6 8 4 .2 8 3 .4 5 2 2 2 3 3 3 2 2 2 18 19 2 0 ,2 1 18 19 2 0 ,2 1 18 19 2 0 ,2 1 1 :4 -1 0 1 :4 -1 1 1 :4 -1 2 2 :4 -1 0 2 :4 -1 1 2 :4 -1 2 3 :4 -1 0 3 :4 -1 1 3 :4 -1 2 0 .7 0 0 .5 3 0 .6 6 0 .6 7 0 .7 1 0 .7 7 0 .5 4 0 .6 6 0 .6 1 0 .2 6 0 .0 8 0 .0 9 0 .1 0 0 .1 0 0 .0 8 0 .0 7 0 .0 8 0 .0 7 1 .7 8 1 .3 4 1 .6 3 1 .6 8 1 .6 8 1 .8 6 1 .2 5 1 .5 3 1 .4 2 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 2 .7 4 1 .9 4 2 .3 8 2 .4 5 2 .4 9 2 .7 2 1 .8 6 2 .2 7 2 .1 0 1 .6 8 9 3 .1 4 3 2 3 .2 5 4 5 2 .7 1 3 3 4 .6 4 0 7 5 .2 0 7 5 2 .0 4 1 3 .4 4 6 4 3 .9 5 4 9 5 9 .5 1 1 6 .4 1 1 2 .2 5 8 .8 5 1 1 6 .5 5 1 1 1 .8 5 5 8 .7 1 1 7 .4 5 1 1 2 .9 2 2 2 3 3 3 2 2 2 22 2 4 ,2 5 2 3 ,2 6 ,2 7 22 2 4 ,2 5 2 3 ,2 6 ,2 7 22 2 4 ,2 5 2 3 ,2 6 ,2 7 1 :5 -1 3 1 :5 -1 4 1 :5 -1 5 2 :5 -1 3 2 :5 -1 4 2 :5 -1 5 3 :5 -1 3 3 :5 -1 4 3 :5 -1 5 0 .7 0 0 .5 9 0 .6 4 0 .7 2 0 .6 1 0 .7 9 0 .5 9 0 .5 1 0 .5 8 0 .1 3 0 .2 4 0.11 0.11 0 .1 0 0 .1 4 0 .2 2 0 .2 0 0.11 1 .8 0 1 .5 0 1 .7 6 1 .7 4 1 .4 9 1 .9 7 1 .4 7 1 .2 5 1 .3 6 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 2 .6 4 2 .3 2 2 .5 1 2 .5 7 2 .1 9 2 .9 0 2 .2 7 1 .9 6 2 .0 4 3 .1 9 5 2 .9 4 0 8 2 .6 3 9 9 4 .9 7 1 2 4 .4 8 3 3 3 .7 6 7 3 .6 1 1 3 3 .3 5 2 2 2 .7 0 3 4 1 1 0 .7 8 8 .3 5 8 4 .6 1 1 1 .6 8 8 .5 8 5 .5 5 1 1 2 .8 5 8 8 .9 8 5 .5 2 2 2 3 3 3 2 2 2 2 8 ,2 9 31 3 0 ,3 2 2 8 ,2 9 31 3 0 ,3 2 2 8 ,2 9 31 3 0 ,3 2 1 :6 -1 6 1 :6 -1 7 1 :6 -1 8 2 :6 -1 6 2 :6 -1 7 2 :6 -1 8 3 :6 -1 6 3 :6 -1 7 3 :6 -1 8 0 .6 6 0 .6 8 0 .6 6 0 .6 0 0 .7 7 0 .6 2 0 .5 3 0 .5 9 0 .6 6 0 .0 9 0 .0 9 0 .0 9 0 .1 0 0 .0 7 0 .0 9 0 .0 7 0 .0 7 0 .0 8 1.71 1.71 1 .7 3 1 .5 5 1.91 1 .5 9 1 .2 7 1 .3 6 1.61 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 2 .4 7 2 .4 8 2 .4 8 2 .2 5 2 .7 5 2 .2 9 1 .8 7 2 .0 2 2 .3 4 2 .5 0 3 6 2 .7 0 8 3 2 .3 5 5 4 3 .9 6 8 4 3 .9 6 7 8 3 .5 6 6 6 2 .9 0 7 6 3 .2 4 4 9 2 .7 6 4 3 87.1 1 1 2 .8 8 5 .4 8 7 .1 5 1 1 2 .4 5 8 4 .5 5 8 7 .6 5 1 1 1 .9 5 8 4 .6 5 2 2 2 3 3 3 2 2 2 3 3 ,3 4 ,3 5 3 6 ,3 7 3 8 ,3 9 3 3 ,3 4 ,3 5 3 6 ,3 7 3 8 ,3 9 3 3 ,3 4 ,3 5 3 6 ,3 7 3 8 ,3 9 1 :7 -1 9 1 :7 -2 0 1 :7 -2 1 2 :7 -1 9 2 :7 -2 0 2 :7 -2 1 3 :7 -1 9 3 :7 -2 0 3 :7 -2 1 0 .7 5 0 .6 8 0 .7 2 0 .6 4 0 .7 8 0 .6 9 0 .5 9 0 .5 9 0 .6 0 0 .1 0 0 .0 9 0 .0 9 0.31 0 .1 0 0 .2 4 0 .0 7 0 .0 7 0 .0 5 1.91 1 .7 2 1 .7 7 1 .4 7 1 .8 4 1 .6 4 1 .3 8 1 .4 2 1 .3 9 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 2 .7 6 2 .4 9 2 .5 7 2 .4 2 2 .7 3 2 .5 7 2 .0 4 2 .0 8 2 .0 5 1 .9 6 9 7 2 .0 7 9 8 2 .6 7 0 5 3 .4 4 7 7 3 .2 6 4 6 4 .3 0 5 9 2 .5 1 1 7 2 .4 3 6 9 3 .4 1 0 7 8 1 .3 5 8 2 .2 5 1 0 1 .0 5 8 2 .3 5 8 2 .7 5 1 0 1 .9 5 8 3 .5 8 3 .3 5 1 0 3 .2 2 2 2 3 3 3 2 2 2 total neutrol sterols excretion (pm ol/100 g r m ouse/day) 3 .1 6 4 .0 1 2 .9 9 3 .7 0 4 .0 4 3 .7 8 3 .7 3 4 .0 9 3 .3 7 3 .6 5 0 .3 9 4 .0 0 4 .0 3 3 .7 0 3 .7 3 4 .8 0 4 .2 1 4 .0 8 3 .4 2 4 .1 8 4 .0 2 0 .3 9 4 .0 7 3 .5 8 3 .7 6 4 .6 2 3 .7 5 4 .0 8 4 .3 6 3 .5 3 3 .7 6 3 .9 5 0 .3 7 3 .8 9 2 .6 2 3 .4 5 3 .7 7 3 .3 1 4 .2 1 3 .2 4 3 .3 3 3 .6 8 3 .5 0 0 .4 6 3 .8 1 3 .8 6 3 .9 2 3 .8 2 3 .7 0 4 .2 5 3 .6 4 3 .6 9 3 .2 3 3 .7 7 0 .2 7 3 .5 4 2 .9 8 3 .4 3 3 .4 2 3 .2 3 3 .2 2 3 .1 0 2 .9 3 3 .8 3 3 .3 0 0 .2 9 3 .3 5 3 .1 4 3 .4 0 3 .3 7 3 .5 9 3 .6 2 3 .0 7 3 .0 5 3 .3 8 3 .3 3 0 .2 1 cam pesterol 2 4 .9 6 2 5 .4 8 2 5 .9 4 2 7 .0 0 2 6 .2 7 2 5 .6 6 2 6 .9 1 2 6 .9 3 2 6 .9 5 2 6 .2 3 0 .7 6 2 5 .1 2 2 5 .5 3 2 5 .1 8 2 7 .1 4 2 5 .7 8 2 6 .2 7 2 6 .6 4 2 8 .3 2 2 6 .0 2 2 6 .2 2 1 .0 3 2 5 .3 8 2 5 .7 6 2 6 .7 1 2 6 .0 4 2 6 .4 3 2 6 .4 8 2 6 .9 4 2 7 .0 7 2 7 .5 1 2 6 .4 8 0 .6 7 2 5 .5 8 2 7 .2 0 2 7 .6 5 2 7 .4 6 2 8 .4 9 2 8 .2 8 2 8 .7 9 2 8 .9 2 2 9 .1 1 2 7 .9 4 1.11 2 6 .5 5 2 5 .2 4 2 5 .4 0 2 7 .7 8 2 7 .7 0 2 7 .1 0 2 5 .8 6 2 5 .8 0 2 8 .2 6 2 6 .6 3 1 .1 2 2 6 .8 9 2 7 .3 5 2 6 .6 6 2 6 .8 5 2 8 .0 5 2 6 .9 5 2 8 .4 7 2 8 .9 8 2 8 .1 3 2 7 .5 9 0 .8 3 2 7 .1 5 2 7 .3 5 2 7 .8 7 2 6 .3 7 2 8 .7 7 2 6 .7 8 2 8 .8 2 2 8 .5 4 2 9 .2 5 2 7 .8 8 1 .0 2 % o f neutral sterols s tig m a ste ro l b -sito s te ro l 8 .3 3 6 6 .7 1 8 .9 1 6 5 .6 1 8 .7 7 6 5 .2 9 6 .3 2 6 6 .6 8 9 .1 5 6 4 .5 8 8 .1 5 6 6 .1 8 8 .4 5 6 4 .6 3 6 .4 9 6 6 .5 7 9 .2 1 6 3 .8 5 8 .2 0 6 5 .5 7 1 .0 8 1 .0 5 9 .2 9 6 5 .5 9 9 .4 0 6 5 .0 7 8 .7 2 6 6 .1 0 4 .7 7 6 8 .0 9 9 .4 5 6 4 .7 7 5 .6 9 6 8 .0 5 8 .7 0 6 4 .6 6 8 .2 1 6 3 .4 7 8 .8 4 6 5 .1 3 8 .1 2 6 5 .6 6 1 .7 0 1 .5 4 9 .2 0 6 5 .4 2 9 .0 9 6 5 .1 5 4 .9 1 6 8 .3 8 9 .0 7 6 4 .8 9 8 .0 2 6 5 .5 5 4 .9 5 6 8 .5 7 9 .3 9 6 3 .6 7 8 .4 8 6 4 .4 6 5 .8 1 6 6 .6 8 7 .6 6 6 5 .8 6 1 .8 9 1 .6 9 9 .6 6 6 4 .7 6 3 .8 7 6 8 .9 3 3 .6 7 6 8 .6 8 3 .9 6 6 8 .5 8 4 .0 1 6 7 .5 0 3 .0 9 6 8 .6 3 3 .9 1 6 7 .3 0 3 .4 2 6 7 .6 6 3 .4 2 6 7 .4 6 4 .3 3 6 7 .7 2 2 .0 2 1 .2 8 5 .0 9 6 8 .3 7 1 0 .2 3 6 4 .5 3 4 .4 7 7 0 .1 4 4 .4 5 6 7 .7 7 4 .4 1 6 7 .8 8 4 .8 1 6 8 .0 9 9 .4 9 6 4 .6 5 1 0 .3 4 6 3 .8 6 5 .1 9 6 6 .5 5 6 .5 0 6 6 .8 7 2 .6 7 2 .1 2 3 .7 0 6 9 .4 1 3 .7 3 6 8 .9 2 3 .7 0 6 9 .6 4 4 .2 7 6 8 .8 8 2 .5 0 6 9 .4 4 3 .8 4 6 9 .2 1 3 .6 5 6 7 .8 8 3 .6 5 6 7 .3 7 3 .3 8 6 8 .4 9 3 .6 0 6 8 .8 1 0 .4 7 0 .7 6 3 .5 6 6 9 .2 8 3 .4 2 6 9 .2 2 3 .3 6 6 8 .7 7 1 2 .8 4 6 0 .7 9 3 .6 6 6 7 .5 7 9 .3 2 6 3 .9 1 3 .3 4 6 7 .8 4 3 .1 8 6 8 .2 8 2 .6 8 6 8 .0 6 5 .0 4 6 7 .0 8 3 .5 5 2 .8 5 1 b -sito sta n o l 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 0 .0 0 Appendix to TNO-report of 3M-02 Final version 04-12-2006 sterols total neutral sterols coprostanol coprostanon cholesterol cholestanol lathosterol total phvtosterols campesterol stigmasterol b-sitosterol b-sitostanol sterols total neutral sterols coprostanol coprostanon cholesterol cholestanol lathosterol total phvtosterols campesterol stigmasterol b-sitosterol b-sitostanol sterols total neutral sterols coprostanol coprostanon cholesterol cholestanol lathosterol total phvtosterols campesterol stigmasterol b-sitosterol b-sitostanol group 1 vs 2 nn p 9 9 0.050 9 9 1.000 9 9 1.000 9 9 0.040 9 9 0.258 9 9 0.190 9 9 0.113 9 9 0.863 9 9 0.666 9 9 0.931 9 9 1.000 group 2 vs 4 nn p 9 9 0.040 9 9 1.000 9 9 1.000 9 9 0.077 9 9 0.489 9 9 <0.001 9 9 0.024 9 9 0.006 9 9 0.004 9 9 0.024 9 9 1.000 group 3 vs 7 nn p 9 9 0.190 9 9 1.000 9 9 1.000 9 9 0.031 9 9 <0.001 9 9 <0.001 9 9 <0.001 9 9 0.008 9 9 0.040 9 9 0.190 9 9 1.000 group 1 vs 3 nn p 9 9 0.077 9 9 1.000 9 9 1.000 9 9 0.863 9 9 0.546 9 9 0.489 9 9 0.222 9 9 0.546 9 9 0.863 9 9 1.000 9 9 1.000 group 2 vs 5 nn p 9 9 0.666 9 9 1.000 9 9 1.000 9 9 0.605 9 9 0.340 9 9 0.113 9 9 0.136 9 9 0.489 9 9 0.387 9 9 0.387 9 9 1.000 group 4 vs 5 nn p 9 9 0.113 9 9 1.000 9 9 1.000 9 9 0.094 9 9 0.605 9 9 <0.001 9 9 0.190 9 9 0.031 9 9 0.002 9 9 0.387 9 9 1.000 Sterol excretion, p values Mann-Whitney U-test group 1 vs 4 group 1 vs 5 group 1 vs 6 nn p nn p nn p 9 9 <0.001 9 9 0.050 9 0.161 9 9 1.000 9 9 1.000 9 1.000 9 9 1.000 9 9 1.000 9 1.000 9 9 <0.001 9 9 0.546 9 0.489 9 9 0.050 9 9 1.000 9 0.002 9 9 <0.001 9 9 0.008 9 0.010 9 9 0.489 9 9 0.730 9 0.077 9 9 0.002 9 9 0.489 9 0.014 9 9 0.004 9 9 0.258 9 <0.001 9 9 0.001 9 9 0.190 9 <0.001 9 9 1.000 9 9 1.000 9 1.000 group 2 vs 6 group 2 vs 7 group 3 vs 4 nn p nn p nn p 9 9 0.666 9 9 0.113 9 9 0.006 9 9 1.000 9 9 1.000 9 9 1.000 9 9 1.000 9 9 1.000 9 9 1.000 9 9 0.040 9 9 0.003 9 9 0.003 9 9 0.050 9 9 <0.001 9 9 0.136 9 9 0.008 9 9 <0.001 9 9 <0.001 9 9 0.001 9 9 <0.001 9 9 0.063 9 9 0.008 9 9 0.003 9 9 0.006 9 9 <0.001 9 9 0.031 9 9 0.004 9 9 <0.001 9 9 0.113 9 9 0.024 9 9 1.000 9 9 1.000 9 9 1.000 group 4 vs 6 group 4 vs 7 group 5 vs 6 n n E__ n n p n n p 9 9 0.006 9 9 <0.001 9 9 0.190 9 9 1.000 9 9 1.000 9 9 1.000 9 9 1.000 9 9 1.000 9 9 1.000 9 9 <0.001 9 9 <0.001 9 9 0.489 9 9 <0.001 9 9 <0.001 9 9 0.258 9 9 0.011 9 9 <0.001 9 9 0.297 9 9 0.190 9 9 0.340 9 9 0.004 9 9 0.258 9 9 0.796 9 9 0.094 9 9 0.436 9 9 0.297 9 9 <0.001 9 9 0.040 9 9 0.730 9 9 0.024 9 9 1.000 9 9 1.000 9 9 1.000 group 1 vs 7 nn p 9 9 0.605 9 9 1.000 9 9 1.000 9 9 0.024 9 9 <0.001 9 9 <0.001 9 9 0.063 9 9 0.003 9 9 0.050 9 9 0.040 9 9 1.000 group 3 vs 5 nn p 9 9 0.161 9 9 1.000 9 9 1.000 9 9 0.730 9 9 0.931 9 9 0.387 9 9 0.546 9 9 0.730 9 9 0.436 9 9 0.546 9 9 1.000 group 5 vs 7 nn p 9 9 0.094 9 9 1.000 9 9 1.000 9 9 0.190 9 9 0.063 9 9 <0.001 9 9 0.001 9 9 0.031 9 9 0.024 9 9 0.605 9 9 1.000 group 2 vs 3 nn p 9 9 0.489 9 9 1.000 9 9 1.000 9 9 0.222 9 9 0.190 9 9 0.931 9 9 0.796 9 9 0.387 9 9 0.605 9 9 0.730 9 9 1.000 group 3 vs 6 nn p 9 9 0.863 9 9 1.000 9 9 1.000 9 9 0.340 9 9 0.008 9 9 0.190 9 9 0.001 9 9 0.014 9 9 <0.001 9 9 0.001 9 9 1.000 group 6 vs 7 nn p 9 9 0.297 9 9 1.000 9 9 1.000 9 9 0.113 9 9 0.004 9 9 <0.001 9 9 0.863 9 9 0.546 9 9 0.387 9 9 0.094 9 9 1.000 p<0.05 Page A106 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 E4. Fecal fatty acid measurements 1 :1-1 w e ig h t feces 8.6 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 13257 256605 2203 231285 22933 1279 2731 % 2.5 4 8 .4 0.4 4 3 .6 4.3 0.2 0.5 Mg fa tty acid 13.9 269 .5 2.3 242 .9 24.1 1.3 2.9 ng fa tty acid m g feces 1619 31340 269 28247 2801 156 334 nm ol fa tty acid/ m g feces 7 .0 9 1 2 2 .2 3 1.06 9 9 .2 9 9.91 0 .5 6 1.20 to ta l 530293 100 1 5 5 7 0 1 64766 2 4 1 .3 3 C 15:0 1 76166 1 I 1:1-2 w e ig h t fe ce s 10.1 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 16324 404265 3337 411875 37807 2492 1091 % 1.9 46.1 0.4 4 7 .0 4.3 0.3 0.1 Mg fa tty acid 14.8 366 .5 3.0 373 .4 3 4 .3 2.3 1.0 ng fa tty acid m g feces 1465 36288 300 36971 3394 224 98 nm ol fa tty acid/ m g feces 6.42 1 4 1 .5 3 1.18 1 2 9 .9 5 12.01 0 .8 0 0 .3 5 to ta l 877191 100 1 7 9 5 3 1 78739 2 9 2 .2 4 C 15:0 1 88241 1 1:1-3 w e ig h t feces 8.8 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 18959 482473 4337 520971 55946 3057 6151 % 1.7 44.2 0.4 47.7 5.1 0.3 0.6 Mg fa tty acid 14.2 362 .4 3.3 391 .3 4 2 .0 2.3 4.6 ng fa tty acid m g feces 1618 41183 370 44469 4775 261 525 nm ol fa tty acid/ m g feces 7 .0 9 1 6 0 .6 2 1.46 1 5 6 .3 0 16.90 0 .9 3 1.89 to ta l 1091894 100 1 820 .2 1 93201 3 4 5 .1 8 C 15:0 1 106504 1 2:1 -1 w e ig h t fe ce s 7.6 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 8193 210520 1596 214647 24494 1701 2635 % 1.8 4 5 .4 0.3 4 6 .3 5.3 0.4 0.6 Mg f a tty a c id 7.5 1 9 3 .9 1.5 1 9 7 .7 2 2 .6 1.6 2.4 ng fa tty acid m g feces 993 25508 193 26008 2968 206 319 nm ol fa tty acid/ m g feces 4 .3 5 99.49 0 .7 6 91.42 10.51 0 .7 3 1.15 to ta l 1 463786 T 100 1 4274 1 56196 r 208 .40 C 15:0 1 86874 1 2:1-2 w e ig h t fe c e s 5 .7 mg | C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 7613 201403 1437 196561 19865 1352 2147 % 1.8 4 6 .8 0.3 4 5 .7 4.6 0.3 0.5 Mg f a tty a c id 6.7 1 7 6 .8 1.3 1 7 2 .5 1 7 .4 1.2 1.9 ng fa tty acid m g feces 1172 31014 221 30268 3059 208 331 nm ol fa tty acid/ m g feces 5 .1 3 1 2 0 .9 6 0 .8 7 1 0 6 .3 9 1 0 .8 3 0 .7 4 1.19 to ta l 1 430378 T 100 1 3778 1 66274 T 2 4 6 .1 1 C 15:0 1 91143 1 2:1-3 w e ig h t fe ce s 7.2 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 9801 284195 2725 348778 35118 2252 4534 % 1.4 4 1 .3 0.4 5 0 .7 5.1 0.3 0.7 Mg f a tty a c id 9.1 2 6 3 .4 2.5 3 2 3 .3 3 2 .6 2.1 4.2 ng fa tty acid m g feces 1262 36587 351 44901 4521 290 584 nm ol fa tty acid/ m g feces 5 .5 2 1 4 2 .7 0 1 .3 8 1 5 7 .8 3 1 6 .0 0 1 .0 3 2 .1 0 to ta l 1 687403 T 100 1 6 37 2 1 88496 T 326 .56 C 15:0 1 86307 1 m olw C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 228 .4 256 .4 254 .4 284 .5 282 .5 280 .5 2 7 8 .5 M Y S T R IC A C ID P A LM ITIC A C ID P A LM IT O LE IC A C ID S T E A R IC A C ID O LE IC A C ID LIN O LE IC A C ID LIN O LE N IC A C ID Page A107 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 | 3:1-1 w eight feces 7.3 mg C 1 4:0 C 1 6:0 C 1 6:1 C 1 8:0 C 1 8:1 C 1 8 :2 C 1 8 :3 area 5463 156085 1332 248855 26880 1566 4158 % 1.2 35.1 0.3 56.0 6.0 0.4 0.9 Mg fa tty acid 7.5 2 1 3 .4 1.8 3 4 0 .2 36.8 2.1 5.7 ng fatty acid m g feces 1023 29233 249 46607 5034 293 779 nm ol fatty acid/ m g feces 4.48 114.01 0.98 163.82 17.82 1.05 2.80 to ta l | 444339 | 100 | 607.5 | 83219 | 3 0 4 .9 6 | C 15:0 I 58514 1 I 3:1-2 w eight feces 5.7 ; mg C 1 4:0 C 1 6:0 C 1 6:1 C 1 8:0 C 1 8:1 C 1 8 :2 C 1 8 :3 area 7866 223765 1702 248550 26968 1646 2844 % 1.5 43.6 0.3 48.4 5.3 0.3 0.6 Mg fa tty acid 7.3 2 0 8 .6 1.6 2 3 1 .7 25.1 1.5 2.7 ng fatty acid m g feces 1287 36598 278 40651 4411 269 465 nm ol fatty acid/ m g feces 5.63 142.74 1.09 142.89 15.61 0.96 1.67 to ta l | 513341 | 100 | 478.6 | 83959 | 3 1 0 .5 9 | C 15:0 I 85813 1 3 j 3 ___________ __________________________________________________ w eight feces 8.3 mg C 1 4:0 C 1 6:0 C 1 6:1 C 1 8:0 C 1 8:1 C 1 8 :2 C 1 8 :3 area 11108 319405 2509 380522 37736 2443 5057 % 1.5 42.1 0.3 50.1 5.0 0.3 0.7 Mg fa tty acid 9.5 2 7 4 .4 2.2 3 2 6 .9 32.4 2.1 4.3 ng fatty acid m g feces 1150 33063 260 39390 3906 253 523 nm ol fatty acid/ m g feces 5.03 128.95 1.02 138.45 13.83 0.90 1.88 to ta l I 758780 | 100 | 651.9 | 78546 | 2 9 0 .0 7 | C 15:0 I 93112 1 1:2-4 w eight feces 13.4 mg C 1 4 :0 C 1 6 :0 C16:1 C 1 8 :0 C18:1 C 1 8 :2 C 1 8 :3 area 27893 881387 8053 1181866 109775 5394 17094 % 1.2 39.5 0.4 53.0 4.9 0.2 0.8 Mg fa tty acid 20.7 654.1 6.0 877.0 81.5 4.0 12.7 ng fatty acid mg feces 1545 48810 446 65450 6079 299 947 nm ol fatty acid/ mg feces 6.76 190.37 1.75 2 3 0 .0 5 21.52 1.06 3.40 to ta l I 2231462 I 100 | 1655.9 | 123575 | 4 5 4 .9 2 | C 15:0 I 107806 1 1:2-5 w eight feces 9.2 mg C 1 4 :0 C 1 6 :0 C16:1 C 1 8 :0 C18:1 C 1 8 :2 C 1 8 :3 area 31737 923618 93 1135022 147397 7383 16098 % 1.4 40.8 0.0 50.2 6.5 0.3 0.7 Mg fa tty acid 19.1 557.2 0.1 684.7 88.9 4.5 9.7 ng fatty acid mg feces 2081 60560 6 74421 9665 484 1056 nm ol fatty acid/ mg feces 9.11 2 3 6 .1 9 0.02 2 6 1 .5 9 34.21 1.73 3.79 to ta l I 2261348 I 100 | 1364.1 | 148272 | 5 4 6 .6 4 | C 15:0 I 132620 1 1 :2-6 w eight feces 9 area C 1 4 :0 C 1 6 :0 C16:1 C 1 8 :0 C18:1 C 1 8 :2 C 1 8 :3 10087 262021 2302 272616 27573 1825 3059 to ta l I 579483 I C 15:0 I 123199 1 mg % 1.7 45.2 0.4 47.0 4.8 0.3 0.5 Mg fa tty acid 6.6 170.1 1.5 177.0 17.9 1.2 2.0 ng fatty acid mg feces 728 18905 166 19669 1989 132 221 nm ol fatty acid/ mg feces 3.19 73.73 0.65 69.14 7.04 0.47 0.79 100 | 376.3 | 41810 | 1 5 5 .0 1 Page A108 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 2:2-4 w eight feces 9.7 mg C 1 4:0 C 1 6:0 C 1 6:1 C 1 8:0 C 1 8:1 C 1 8:2 C 1 8:3 area 18615 488224 4357 581814 60179 3098 7073 % 1.6 42.0 0.4 50.0 5.2 0.3 0.6 Mg fa tty acid 15.3 4 0 1 .8 3.6 4 7 8 .8 49.5 2.5 5.8 ng fatty acid mg feces 1579 41421 370 49361 5106 263 600 nm ol fatty acid/ mg feces 6.91 161.55 1.45 173.50 18.07 0.94 2.15 to ta l I 1163360 I 100 | 957.4 | 98699 | 3 6 4 .5 8 | C 15:0 I 97212 I 3:2-4 w e ig h t fe ce s 8.6 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 18311 420511 3649 545499 56501 3001 7025 % 1.7 3 9 .9 0.3 51.7 5.4 0.3 0.7 Mg fa tty acid 15.1 3 4 6 .4 3.0 4 4 9 .4 46.5 2.5 5.8 ng fa tty acid m g feces 1754 40284 350 52257 5413 287 673 nm ol fa tty acid/ m g feces 7.68 157.11 1.37 1 8 3 .6 8 19.16 1.02 2.42 to ta l | 1054497 | 100 | 868.7 | 101017 | 372~45 C 15:0 | 97105 | w eight feces C 1 4:0 C 1 6:0 C 1 6:1 C 1 8:0 C 1 8:1 C 1 8:2 C 1 8:3 9.3 area 18128 549910 5378 733331 85796 4289 10396 mg % 1.3 39.1 0.4 52.1 6.1 0.3 0.7 Mg fa tty acid 14.7 4 4 4 .5 4.3 5 9 2 .7 69.3 3.5 8.4 ng fatty acid mg feces 1575 47793 467 63734 7457 373 904 nm ol fatty acid/ mg feces 6.90 186.40 1.84 2 2 4 .0 2 26.39 1.33 3.24 to ta l J1 1 4 0 7 2 2 8 11 100 11 1 1 3 7 .4 11 1 2 2 3 0 2 1 4 5 0 .1 2 1 C 15:0 11 9 8 9 7 8 1 2:2-6 w eight feces C 1 4:0 C 1 6:0 C 1 6:1 C 1 8:0 C 1 8:1 C 1 8:2 C 18:3 59 area 5981 103637 790 97059 10984 884 1019 mg % 2.7 47.0 0.4 44.0 5.0 0.4 0.5 i Mg fa tty acid 4.9 84.2 0.6 78.9 8.9 0.7 0.8 ng fatty acid mg feces 824 14272 109 13366 1513 122 140 nm ol fatty acid/ mg feces 3.61 55.66 0.43 46.98 5.35 0.43 0.50 total 220354 100 1 T T ^ 1 30345 112.97 C15:0 1 98463 1 w e ig h t fe c e s 7.7 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 14837 453886 4567 591094 63874 3296 7991 % 1.3 3 9 .8 0.4 5 1 .9 5.6 0.3 0.7 Mg fa tty acid 11.7 3 5 6 .9 3.6 4 6 4 .8 50.2 2.6 6.3 ng fa tty acid m g feces 1515 46352 466 60364 6523 337 816 nm ol fa tty acid/ m g feces 6.63 1 8 0 .7 8 1.83 2 1 2 .1 8 2 3 .0 9 1.20 2.93 to ta l J1 1 1 3 9 5 4 5 11 1 0 0 11 8 9 6 .1 11 1 1 6 3 7 4 11 4 2 8 .6 5 1 C 15:0 1 101736 1 3:2-6 w e ig h t fe c e s 8 .4 mg area % C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 5585 169177 1364 196952 20806 1530 2302 1.4 4 2 .5 0.3 4 9 .5 5.2 0.4 0.6 to ta l 397716 100 C 15:0 1 9098T I Mg fa tty acid 4.9 1 4 8 .8 1.2 1 7 3 .2 18.3 1.3 2.0 ng fa tty acid m g feces 585 17709 143 20617 2178 160 241 nm ol fa tty acid/ m g feces 2.56 6 9 .0 7 0.56 7 2 .4 7 7.71 0.57 0.87 349 7 I 41633 1 5 3 .8 0 Page A109 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 1:3-7 w e ig h t feces 11 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 14517 354931 3055 369554 36484 2417 4404 % 1.8 4 5 .2 0 .4 47.1 4.6 0.3 0.6 Mg f a tty acid 10.1 245 .8 2.1 256 .0 2 5 .3 1.7 3.1 ng fa tty acid m g feces 914 22349 192 23269 2297 152 277 nm ol fa tty acid/ m g feces 4 .0 0 8 7 .1 6 0 .7 6 8 1 .7 9 8 .1 3 0 .5 4 1.00 to ta l I 785362 I 100 | 544 .0 | 49451 | 183 .38 | C 1 5:0 I 115502 1 237 w e ig h t fe ce s 8.3 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 7895 202071 1616 212839 21090 1476 2397 % 1.8 4 5 .0 0.4 4 7 .4 4.7 0.3 0.5 Mg f a tty a c id 6.9 1 7 7 .0 1.4 186 .4 18.5 1.3 2.1 ng fa tty acid m g feces 833 21327 171 22464 2226 156 253 nm ol fa tty acid/ m g feces 3 .6 5 8 3 .1 8 0 .6 7 7 8 .9 6 7 .8 8 0 .5 6 0.91 to ta l I 449384 I 100 | 393 .7 | 47429 | 175 .80 | C 1 5:0 I 91324 1 I 1:3-8 w e ig h t fe ce s 11.1 mg I 2:3-8 w e ig h t fe c e s 7.6 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 20655 613614 5769 774403 72889 4402 10243 % 1.4 4 0 .9 0 .4 5 1 .6 4.9 0.3 0.7 Mg f a tty acid 11.8 350 .2 3.3 441 .9 4 1 .6 2.5 5.8 ng fa tty acid m g feces 1062 31548 297 39815 3747 226 527 nm ol fa tty acid/ m g feces 4 .6 5 123 .04 1.17 1 3 9 .9 5 1 3 .2 7 0.81 1.89 C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 13707 374445 3351 433392 46483 2770 5202 % 1.6 4 2 .6 0.4 4 9 .3 5.3 0.3 0.6 Mg f a tty a c id 9.9 269 .9 2.4 312 .4 3 3 .5 2.0 3.8 ng fa tty acid m g feces 1300 35519 318 41111 4409 263 493 nm ol fa tty acid/ m g feces 5 .6 9 1 3 8 .5 3 1 .2 5 1 4 4 .5 0 15.61 0 .9 4 1 .7 7 to ta l I 1501975 I 100 | 857 .2 | 77221 | 2 8 4 .7 7 | to ta l I 879350 I 100 | 633 .9 | 834 14 | 3 0 8 .2 9 | C 1 5:0 I 140182 1 C 1 5:0 I 110969 1 I 1:3-9 w e ig h t fe ce s 1 3 .4 mg area % C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 26223 851207 7949 1186581 108707 7434 16281 1.2 3 8 .6 0 .4 5 3 .8 4.9 0.3 0.7 to ta l 2204382 100 C 15:0 1 144789 I Mg f a tty acid 14.5 470 .3 4 .4 655 .6 60.1 4.1 9.0 ng fa tty acid m g feces 1081 35098 328 48927 4482 307 671 nm ol fa tty acid/ m g feces 4 .7 3 1 3 6 .8 9 1.29 1 7 1 .9 7 1 5 .8 7 1.09 2.41 121 8.0 1 908 94 334 .26 I 2:3-9 w e ig h t fe c e s 7 .4 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 9500 267057 2386 302932 29071 2020 3014 % 1.5 4 3 .4 0.4 4 9 .2 4.7 0.3 0.5 Mg f a tty a c id 7.5 210 .9 1.9 239 .2 2 3 .0 1.6 2 .4 ng fa tty acid m g feces 1014 28499 255 32327 3102 216 322 nm ol fa tty acid/ m g feces 4 .4 4 1 1 1 .1 5 1 .0 0 1 1 3 .6 3 1 0 .9 8 0 .7 7 1 .1 5 to ta l 1 615980 T 100 1 4 8 6 1 11 6 5 7 3 4 T 243 .12 C 15:0 I 101306 I Page A110 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 I 3:3-7 w e ig h t fe ce s 8.5 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 7543 193432 1421 205498 21652 1375 2581 % 1.7 4 4 .6 0.3 4 7 .4 5.0 0.3 0.6 Mg fa tty a c id 6 .4 1 6 4 .2 1.2 174 .4 1 8 .4 1.2 2.2 ng fa tty acid m g feces 753 19312 142 20517 2162 137 258 nm ol fa tty acid/ m g feces 3 .3 0 75.32 0 .5 6 72.12 7 .6 5 0 .4 9 0 .9 3 to ta l I 433502 I 100 | 367 .9 | 43281 | 160 .36 | C 1 5:0 I 94269 1 I 3:3-8 w e ig h t fe ce s 6.5 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 6822 183086 1710 197892 21000 1164 2282 % 1.6 4 4 .2 0.4 4 7 .8 5.1 0.3 0.6 Mg fa tty a c id 6 .4 1 7 2 .2 1.6 186.1 19.7 1.1 2.1 ng fa tty acid m g feces 987 26486 247 28628 3038 168 330 nm ol fa tty acid/ m g feces 4 .3 2 1 0 3 .3 0 0 .9 7 1 0 0 .6 3 1 0 .7 5 0 .6 0 1.19 to ta l 1 413956 T 100 1 3 80 1 1 59885 r 221 .76 I C 15:0 I 85077 I I 3:3-9 w e ig h t fe ce s 14 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 13974 420919 4038 511096 49923 3410 6144 % 1.4 4 1 .7 0.4 5 0 .6 4.9 0.3 0.6 Mg fa tty a c id 1 2 .4 372 .5 3.6 452 .3 4 4 .2 3.0 5.4 ng fa tty acid m g feces 883 26609 255 32310 3156 216 388 nm ol fa tty acid/ m g feces 3 .8 7 1 0 3 .7 8 1 .0 0 1 1 3 .5 7 1 1 .1 7 0 .7 7 1.39 to ta l 1 1009504 I 100 1 8935 1 63818 r 235 .56 1 C 15:0 I 90391 1 1:4-10 w e ig h t feces 8.2 area C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 16048 495415 3727 599026 56734 3322 7505 to ta l I 1181777 I C 15:0 I 115946 1 mg % 1.4 41.9 0.3 50.7 4.8 0.3 0.6 MS fa tty acid 11.1 3 4 1 .8 2.6 4 1 3 .3 39.1 2.3 5.2 ng fa tty acid mg feces 1350 41686 314 50404 4774 280 631 nm ol fa tty acid/ mg feces 5.91 1 6 2 .5 8 1.23 1 7 7 .1 7 16.90 1.00 2.27 100 | 815.4 | 99439 | 367 .06 | 1:4-11 w e ig h t feces 8.8 mg area % C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 13693 392497 3202 454998 43482 2667 5468 1.5 42.8 0.3 49.7 4.7 0.3 0.6 to ta l 916007 100 C 15:0 1 128901 I M3 fa tty acid 8.5 2 4 3 .6 2.0 2 8 2 .4 27.0 1.7 3.4 ng fa tty acid mg feces 966 27681 226 32089 3067 188 386 nm ol fa tty acid/ mg feces 4 .2 3 1 0 7 .9 6 0 .8 9 1 1 2 .7 9 10.86 0.67 1.38 568 5 I 64603 2 3 8 .7 8 1:4-12 w e ig h t feces 9.8 mg area % C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 11857 361984 2570 460388 51833 3265 5863 1.3 40.3 0.3 51.3 5.8 0.4 0.7 to ta l 897760 100 C 15:0 1 76774 1 Mg fa tty acid 12.4 3 7 7 .2 2.7 4 7 9 .7 54.0 3.4 6.1 ng fa tty acid mg feces 1261 38489 273 48952 5511 347 623 nm ol fa tty acid/ mg feces 5.52 150.11 1.07 1 7 2 .0 6 19.51 1.24 2 .2 4 9 3 5 5 1 95457 351 .76 1 Page A111 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 2:4-10 w e ig h t fe ce s 7.1 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 10522 344618 2591 438053 40213 2602 5292 % 1.2 4 0 .8 0.3 5 1 .9 4.8 0.3 0.6 Mg f a tty acid 8.5 2 7 8 .0 2.1 3 5 3 .4 3 2 .4 2.1 4.3 ng fa tty acid mg feces 1196 39156 294 49772 4569 296 601 nm ol fa tty acid/ m g feces 5 .2 3 152.71 1.16 1 7 4 .9 4 16.17 1.05 2 .1 6 to ta l 843891 100 1 680 .8 1 95883 3 5 3 .4 4 C 15:0 1 99169 1 2:4-11 w e ig h t fe ce s 8.7 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 13021 381006 3180 444595 44296 2954 4928 % 1.5 4 2 .6 0.4 49.7 5.0 0.3 0.6 Mg f a tty acid 10.2 2 9 7 .9 2.5 3 4 7 .6 3 4 .6 2.3 3.9 ng fa tty acid mg feces 1170 34238 286 39952 3981 265 443 nm ol fa tty acid/ m g feces 5.12 1 3 3 .5 3 1.12 1 4 0 .4 3 14.09 0 .9 5 1.59 to ta l 893980 100 1 698 .9 1 80335 2 9 6 .8 4 C 15:0 1 102328 1 2:4-12 w e ig h t fe ce s 7.2 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 12246 332981 2528 357246 40701 2826 3646 % 1.6 4 4 .3 0.3 4 7 .5 5.4 0.4 0.5 Mg f a tty acid 9.2 2 4 9 .3 1.9 2 6 7 .5 3 0 .5 2.1 2.7 ng fa tty acid mg feces 1273 34627 263 37150 4232 294 379 nm ol fa tty acid/ m g feces 5 .5 8 1 3 5 .0 5 1.03 1 3 0 .5 8 14.98 1.05 1.36 to ta l 752174 100 1 5 6 3 2 1 78218 2 8 9 .6 3 C 15:0 1 106848 1 3:4-10 w e ig h t fe ces 8.5 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 10172 310431 2449 394129 34766 2260 4580 % 1.3 4 0 .9 0.3 5 1 .9 4.6 0.3 0.6 Mg fa tty acid 9.5 2 8 8 .5 2.3 3 6 6 .3 3 2 .3 2.1 4.3 ng fa tty acid mg feces 1112 33946 268 43098 3802 247 501 nm ol fa tty acid/ mg feces 4.87 1 3 2 .3 9 1.05 1 5 1 .4 9 13.46 0.88 1.80 to ta l 1 758787 T 100 1 7 05 3 1 82973 r 3 0 5 .9 4 1 C 15:0 1 86070 1 3:4-11 w e ig h t fe ces 9.8 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 20169 422311 3653 565589 52273 2913 7488 % 1.9 3 9 .3 0.3 5 2 .6 4.9 0.3 0.7 Mg fa tty acid 17.5 367.1 3.2 4 9 1 .7 4 5 .4 2.5 6.5 ng fa tty acid mg feces 1789 37462 324 50171 4637 258 664 nm ol fa tty acid/ mg feces 7.83 146.11 1.27 1 7 6 .3 5 16.41 0.92 2.39 to ta l 1 1074396 1 100 1 9 3 4 0 1 95305 T 351.28 I C 15:0 1 92026 1 3:4-12 w e ig h t fe ces 10.7 mg area % C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 15056 501243 4206 708410 68397 4333 9322 1.1 38.2 0.3 5 4 .0 5.2 0.3 0.7 to ta l 1310967 100 C 15:0 1 87759 1 Mg fa tty acid 13.7 4 5 6 .9 3.8 6 4 5 .8 6 2 .3 3.9 8.5 ng fa tty acid mg feces 1283 42703 358 60353 5827 369 794 nm ol fa tty acid/ mg feces 5.62 1 6 6 .5 5 1.41 2 1 2 .1 4 2 0 .6 3 1.32 2.85 1195.1 1 111688 4 1 0 .5 1 1 Page A112 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 1:5-13 w e ig h t feces 8.3 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 13526 393457 3030 473949 44962 3228 5563 % 1.4 4 2 .0 0.3 5 0 .5 4.8 0.3 0.6 Mg fa tty acid 9.5 2 7 5 .2 2.1 3 3 1 .6 3 1 .5 2.3 3.9 ng fa tty acid mg feces 1140 33162 255 39947 3790 272 469 nm ol fa tty acid/ m g feces 4 .9 9 1 2 9 .3 4 1.00 140.41 13.41 0.97 1.68 to ta l I 937715 I 100 | 656.0 | 790 35 | 2 9 1 .8 1 | C 1 5:0 I 114357 1 2:5-13 w e ig h t feces 8.1 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 13428 386269 3253 437237 45693 2448 5034 % 1.5 43.2 0.4 4 8 .9 5.1 0.3 0.6 Mg fa tty acid 10.8 3 1 0 .0 2.6 3 5 0 .9 36.7 2.0 4.0 ng fa tty acid mg feces 1331 38276 322 43327 4528 243 499 nm ol fa tty acid/ mg feces 5 .8 3 1 4 9 .2 8 1.27 1 5 2 .2 9 16.03 0.86 1.79 to ta l I 8 9 3 3 6 2 I 100 | 717.1 | 8 8 5 2 5 | 327 .35 | C 1 5:0 I 996 70 1 I 1:5-14 w e ig h t fe ce s 11 mg I C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 33483 1006010 9704 1300166 160875 7669 18973 % 1.3 39.7 0.4 5 1 .3 6.3 0.3 0.7 Mg fa tty acid 19.7 5 9 2 .1 5.7 7 6 5 .3 94.7 4.5 11.2 ng fa tty acid mg feces 1792 53832 519 69572 8608 410 1015 nm ol fa tty acid/ m g feces 7 .8 4 2 0 9 .9 5 2 .0 4 2 4 4 .5 4 3 0 .4 7 1.46 3 .6 5 to ta l I 2536880 I 100 | 1493.2 | 135749 | 499 .96 | C 1 5:0 I 135913 1 I 2:5-14 w e ig h t fe ce s C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 9 .9 area 23143 686470 6696 830835 105595 4899 10267 mg % 1.4 41.2 0.4 4 9 .8 6.3 0.3 0.6 Mg fa tty acid 17.1 5 0 8 .5 5.0 6 1 5 .4 78.2 3.6 7.6 ng fa tty acid mg feces 1731 51359 501 62160 7900 367 768 nm ol fa tty acid/ mg feces 7 .5 8 2 0 0 .3 1 1.97 218 .49 2 7 .9 7 1.31 2 .7 6 to ta l I 1667905 I 100 | 1235.4 | 124787 | 460 .38 | C 1 5:0 I 108008 1 1:5-15 w e ig h t fe ce s 8 .3 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 11073 294462 2464 315545 28429 1608 3367 % 1.7 4 4 .8 0.4 4 8 .0 4.3 0.2 0.5 Mg fa tty acid 7.3 195.1 1.6 2 0 9 .0 18.8 1.1 2.2 ng fa tty acid mg feces 884 23500 197 25183 2269 128 269 nm ol fa tty acid/ m g feces 3.87 9 1 .6 5 0.77 8 8 .5 2 8 .0 3 0 .4 6 0 .9 6 to ta l 1 656948 T 100 1 4352 1 52429 T 19427 1 C 15:0 1 120773 I 2 : 5 - 1 5 _________________________________________________________________________________ w e ig h t fe ce s 8 .3 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 7030 128252 1016 106592 11903 760 1127 % 2.7 5 0 .0 0.4 4 1 .5 4.6 0.3 0.4 Mg fa tty acid 6.9 126.1 1.0 1 0 4 .8 11.7 0.7 1.1 ng fa tty acid mg feces 833 15190 120 12624 1410 90 133 nm ol fa tty acid/ mg feces 3 .6 5 59.24 0.47 4 4 .3 7 4 .9 9 0.32 0 .4 8 to ta l 256680 100 252-3 1 30401 1 1 3 .5 3 C 15:0 1 8138 1 Page A113 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 3:5-13 w e ig h t feces 6.8 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 26211 674622 5831 907134 95082 4891 12523 % 1.5 39.1 0.3 5 2 .5 5.5 0.3 0.7 Mg f a tty a c id 10.5 269 .2 2.3 362 .0 3 7 .9 2.0 5.0 ng fa tty acid m g feces 1538 39589 342 53233 5580 287 735 nm ol fa tty acid/ m g feces 6 .7 3 1 5 4 .4 0 1.35 187.11 1 9 .7 5 1.02 2 .6 4 to ta l I 1726294 I 100 | 688 .9 | 101 3 0 4 | 3 7 3 .0 1 | C 1 5:0 I 200479 1 I 3:5-14 w e ig h t fe ce s 5 .3 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 12309 339628 3302 368609 45053 2365 4243 % 1.6 4 3 .8 0 .4 4 7 .5 5.8 0.3 0.5 Mg f a tty a c id 10.3 283 .7 2.8 307 .9 3 7 .6 2.0 3.5 ng fa tty acid m g feces 1940 53533 520 58101 7101 373 669 nm ol fa tty acid/ m g feces 8 .4 9 2 0 8 .7 9 2 .0 5 2 0 4 .2 2 2 5 .1 4 1.33 2 .4 0 to ta l 1 775509 T 100 11 6 4 7 9 1 122237 1 452 .42 1 C 15:0 1 95763 1 I 3:5-15 w e ig h t fe ce s 8.1 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 4597 119586 872 128120 13678 939 1419 % 1.7 4 4 .4 0.3 4 7 .6 5.1 0.3 0.5 Mg f a tty a c id 4.7 123.1 0.9 1 3 1 .9 14.1 1.0 1.5 ng fa tty acid m g feces 584 15199 111 16283 1738 119 180 nm ol fa tty acid/ m g feces 2 .5 6 5 9 .2 8 0 .4 4 5 7 .2 3 6 .1 5 0 .4 3 0 .6 5 to ta l 1 269211 T 100 1 2771 1 34215 r 1 2 6 .7 3 I C 15:0 I 7771 1 1:6-16 w e ig h t fe ce s 11.7 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 20396 664144 5241 854148 80539 5034 11097 % 1.2 40.5 0.3 52.1 4.9 0.3 0.7 MS fa tty acid 12.5 4 0 7 .7 3.2 5 2 4 .4 4 9 .4 3.1 6.8 ng fa tty acid mg feces 1070 34849 275 44819 4226 264 582 nm ol fa tty acid/ mg feces 4 .6 9 1 3 5 .9 2 1.08 1 5 7 .5 4 14.96 0 .9 4 2 .0 9 to ta l C 15:0 I 1640599 | : :130309 100 I 1 0 0 7 .2 ~ r 86086 3 1 7 .2 1 1:6-17 w e ig h t fe c e s 8 .9 mg area % C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 12220 366294 3077 427401 40324 2415 5166 1.4 42.7 0.4 49.9 4.7 0.3 0.6 to ta l 856897 100 C 15:0 1 117016 I M3 fa tty acid 8.4 2 5 0 .4 2.1 2 9 2 .2 2 7 .6 1.7 3.5 ng fa tty acid mg feces 939 28137 236 32831 3098 186 397 nm ol fa tty acid/ mg feces 4.11 1 0 9 .7 4 0 .9 3 1 1 5 .4 0 10.96 0.66 1.42 585"8 1 65824 2 4 3 .2 3 1:6-18 w e ig h t fe c e s 10.8 mg area % C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 17671 535579 4357 659139 67882 4052 8388 1.4 41.3 0.3 50.8 5.2 0.3 0.6 to ta l 1297068 100 C 15:0 1 136015 I Mg fa tty acid 10.4 3 1 5 .0 2.6 3 8 7 .7 3 9 .9 2.4 4.9 ng fa tty acid mg feces 962 29168 237 35897 3697 221 457 nm ol fa tty acid/ mg feces 4.21 1 1 3 .7 6 0 .9 3 1 2 6 .1 8 13.09 0 .7 9 1.64 7 62 9 1 70639 2 6 0 .5 9 Page A114 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 2:6-16 weightfeces 12.1 mg area % Mgfatty ngfattyacid nmolfattyacid/ acid mgfeces mgfeces C14:0 16368 1.4 12.4 1028 4.50 C16:0 492848 43.0 374.7 30966 120.77 C16:1 3736 0.3 2.8 235 0.92 C18:0 567463 49.5 431.4 35654 125.32 C18:1 55948 4.9 42.5 3515 12.44 C18:2 3689 0.3 2.8 232 0.83 C18:3 6084 0.5 4.6 382 1.37 total 1146136 100 1 871.4 I 72013 266.16 C15:0 1 105228 I 2:6-17 weightfeces 8.5 mg area % Mgfatty ngfattyacid nmolfattyacid/ acid mgfeces mgfeces C14:0 7619 2.2 7.2 846 3.70 C16:0 165470 48.1 156.1 18369 71.64 C16:1 1010 0.3 1.0 112 0.44 C18:0 151890 44.1 143.3 16862 59.27 C18:1 15484 4.5 14.6 1719 6.08 C18:2 1040 0.3 1.0 115 0.41 C18:3 1620 0.5 1.5 180 0.65 total 344133 100 1 3247 1 38204 142.20 C15:0 1 84780 1 2:6-18 weightfeces 10.2 mg area % Mgfatty ngfattyacid nmolfattyacid/ acid mgfeces mgfeces C14:0 13778 1.8 9.5 928 4.06 C16:0 361552 46.5 248.5 24363 95.02 C16:1 2752 0.4 1.9 185 0.73 C18:0 355381 45.7 244.3 23948 84.17 C18:1 38817 5.0 26.7 2616 9.26 C18:2 2125 0.3 1.5 143 0.51 C18:3 3865 0.5 2.7 260 0.94 total 778270 100 1 5349 1 52444 194.69 C15:0 1 116392 I 3:6-16 weightfeces 9.6 mg area % Mgfatty ngfattyacid nmolfattyacid/ acid mgfeces mgfeces C14:0 11600 1.2 10.6 1109 4.86 C16:0 381872 39.5 350.5 36507 142.38 C16:1 3071 0.3 2.8 294 1.15 C18:0 510655 52.8 468.7 48818 171.59 C18:1 50174 5.2 46.0 4797 16.98 C18:2 2963 0.3 2.7 283 1.01 C18:3 6403 0.7 5.9 612 2.20 total 966738 100 1 8872 1 92420 340.17 C15:0 1 87169 1 3:6-17 weightfeces 7.6 mg area % Mgfatty ngfattyacid nmolfattyacid/ acid mgfeces mgfeces C14:0 6657 1.8 6.5 849 3.72 C16:0 174284 45.8 168.9 22222 86.67 C16:1 1200 0.3 1.2 153 0.60 C18:0 175484 46.1 170.0 22375 78.65 C18:1 19588 5.2 19.0 2498 8.84 C18:2 1351 0.4 1.3 172 0.61 C18:3 1768 0.5 1.7 225 0.81 total 380332 1 11 3087 1 48494 T 179.90 C15:0 1 82557 1 3:6-18 weightfeces 8.1 mg area % Mgfatty ngfattyacid nmolfattyacid/ acid mgfeces mgfeces C14:0 8700 1.3 8.3 1022 4.47 C16:0 277658 41.8 264.1 32606 127.17 C16:1 1872 0.3 1.8 220 0.86 C18:0 334779 50.4 318.4 39313 138.18 C18:1 34667 5.2 33.0 4071 14.41 C18:2 1792 0.3 1.7 210 0.75 C18:3 4339 0.7 4.1 510 1.83 total 1 663807 T 1 6314 1 77952 T 287.68 C15:0 1 84105 1 Page A115 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 1:7-19 w e ig h t feces 10.7 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 9334 205542 1575 189750 23168 1823 1777 % 2.2 4 7 .5 0.4 4 3 .8 5.4 0.4 0.4 Mg fa tty acid 6.0 1 3 1 .2 1.0 121.1 14.8 1.2 1.1 ng fa tty acid m g feces 557 12263 94 11321 1382 109 106 nm ol fa tty acid/ m g feces 2 .4 4 4 7 .8 3 0.37 3 9 .7 9 4 .8 9 0 .3 9 0 .3 8 to ta l I 432969 I 100 | 276 .4 | 25831 | 96.09 C 1 5:0 I 125320 1 2:7-19 w e ig h t feces 12.4 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 10569 262993 1907 260336 26561 1861 2435 % 1.9 4 6 .4 0.3 4 5 .9 4.7 0.3 0.4 Mg fa tty acid 8.5 2 1 2 .5 1.5 2 1 0 .3 2 1 .5 1.5 2.0 ng fa tty acid mg feces 689 17137 124 16963 1731 121 159 nm ol fatty acid/ mg feces 3.02 6 6 .8 4 0 .4 9 5 9 .6 3 6 .1 3 0 .4 3 0.57 to ta l I 566662 | 100 | 457.9 | 369 24 | 1 3 7 .0 9 | C 1 5:0 I 99012 1 I 1:7-20 w e ig h t fe ce s 7.2 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 5300 116241 798 106821 14034 1332 1059 % 2.2 4 7 .3 0.3 4 3 .5 5.7 0.5 0.4 Mg fa tty acid 3.9 86.1 0.6 79.1 10.4 1.0 0.8 ng fa tty acid m g feces 545 11953 82 10984 1443 137 109 nm ol fa tty acid/ m g feces 2 .3 9 4 6 .6 2 0.32 38.61 5.11 0 .4 9 0 .3 9 to ta l I 245585 I 100 | 181.8 | 25 2 5 4 | 9 3 .9 2 C 1 5:0 I 108053 1 I 2:7-20 w e ig h t fe ce s 6 mg I C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 4357 90363 573 77962 9578 799 815 % 2.4 4 9 .0 0.3 4 2 .3 5.2 0.4 0.4 Mg fa tty acid 3.7 75.7 0.5 6 5 .3 8.0 0.7 0.7 ng fa tty acid mg feces 608 12617 80 10886 1337 112 114 nm ol fatty acid/ mg feces 2 .6 6 49.21 0.31 3 8 .2 6 4 .7 3 0 .4 0 0.41 to ta l I 184447 I 100 | 154.5 | 25 7 5 4 | 9 5 .9 9 C 1 5:0 I 954 90 1 I 1:7-21 w e ig h t fe ce s 10 mg I 2:7-21 w e ig h t fe ce s 8.7 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 to ta l area % 9522 270616 2338 313018 37006 3195 3428 1.5 4 2 .3 0.4 4 9 .0 5.8 0.5 0.5 1 639123 T 100 Mg fa tty acid 6.2 1 7 6 .8 1.5 2 0 4 .6 24.2 2.1 2.2 1 4177 ng fa tty acid nm ol fa tty a c id / m g feces m g feces 622 2.72 17684 6 8 .9 7 153 0.60 20455 7 1 .9 0 2418 8 .5 6 209 0.74 224 0.80 r1 4 7 7 6 6 5 4 3 1 C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 to ta l area 7650 212450 1476 217370 22360 1545 2300 465151 % 1.6 45.7 0.3 46.7 4.8 0.3 0.5 100 C 15:0 1 122421 I C 15:0 1 109572 I Mg fa tty acid 5.6 155.1 1.1 1 5 8 .7 16.3 1.1 1.7 ng fa tty acid mg feces 642 17829 124 18242 1876 130 193 nm ol fatty acid/ mg feces 2.81 6 9 .5 4 0 .4 9 6 4 .1 2 6 .6 4 0 .4 6 0 .6 9 339 6 1 39036 1 4 4 .7 5 Page A116 of A172 Appendix to TNO-report of 3M-02 Final version | 3:7-19 w e ig h t fe ce s 5 .8 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 4977 125240 723 123021 11441 691 1184 % 1.9 4 6 .9 0.3 4 6 .0 4.3 0.3 0.4 Mg fa tty acid 4.8 120.0 0.7 1 1 7 .8 1 1 .0 0.7 1.1 ng fa tty acid mg feces 822 20682 119 20316 1889 114 196 nm ol fa tty acid/ m g feces 3 .6 0 8 0 .6 6 0.47 71.41 6 .6 9 0.41 0 .7 0 to ta l | 267277 | 100 | 256 .0 | 441 38 | 1 6 3 .9 4 | C 15:0 | 83524 1 | 3:7-20 w e ig h t fe ce s 7.7 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 5155 125067 811 121012 14616 1143 1266 % 1.9 4 6 .5 0.3 4 5 .0 5.4 0.4 0.5 Mg fa tty acid 4.2 1 0 2 .5 0.7 99.1 1 2 .0 0.9 1.0 ng fa tty acid mg feces 548 13306 86 12875 1555 122 135 nm ol fa tty acid/ m g feces 2 .4 0 5 1 .9 0 0 .3 4 4 5 .2 5 5 .5 0 0 .4 3 0 .4 8 to ta l | 269070 | 100 | 220 .4 | 28627 | 106.31 | C 15:0 | 97655 1 | 3:7-21 w e ig h t fe ce s 17 mg C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 area 11944 374593 3142 460518 44662 3197 5430 % 1.3 4 1 .5 0.3 5 1 .0 4.9 0.4 0.6 Mg fa tty acid 10.3 3 2 1 .7 2.7 3 9 5 .5 3 8 .4 2.7 4.7 ng fa tty acid mg feces 603 18926 159 23268 2257 162 274 nm ol fa tty acid/ m g feces 2 .6 4 7 3 .8 2 0.62 8 1 .7 8 7 .9 9 0 .5 8 0 .9 9 to ta l | 903486 | 100 | 776 .0 | 456 48 | 1 6 8 .4 ~ C 15:0 | 93140 1 04-12-2006 Page A117 of A172 Appendix to TNO-report of 3M-02____________ Final version__________________________04-12-2006 Page A118 of A172 group i i i AVERAGE SD 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 4 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 AVERAGE SD cage# 1,2 3 ,4 5 1,2 3 ,4 5 1,2 3 ,4 5 GC sam ple# 1:1-1 1 :1 -2 1 :1 -3 2 :1 -1 2 :1 -2 2 :1 -3 3 :1 -1 3 :1 -2 3 :1 -3 C 14:0 7 .0 9 6 .4 2 7 .0 9 4 .3 5 5 .1 3 5 .5 2 4 .4 8 5 .6 3 5 .0 3 fatty acids (pm ol/g feces) C 1 6 :0 C 16:1 C 1 8 :0 C 18:1 C 1 8 :2 122 .2 3 1.06 9 9 .2 9 9.91 0 .5 6 141 .5 3 1.18 129.95 12.01 0 .8 0 160.62 1.46 156.30 16.90 0 .9 3 9 9 .4 9 0 .7 6 9 1 .4 2 10.51 0 .7 3 120.96 0 .8 7 106.39 10.83 0 .7 4 142.70 1.38 157.83 16.00 1.03 114.01 0 .9 8 163.82 17.82 1.05 1 4 2 .7 4 1 2 8 .9 5 1 .0 9 1 .0 2 142.89 15.61 138.45 13.83 0 .9 6 0 .9 0 C 18:3 1 .2 0 0 .3 5 1 .8 9 1 .1 5 1 .1 9 2 .1 0 2 .8 0 1 .6 7 1 .8 8 fatty acids total (pm ol/g feces) 2 4 1 .3 3 2 9 2 .2 4 3 4 5 .1 8 2 0 8 .4 0 2 4 6 .1 1 3 2 6 .5 6 3 0 4 .9 6 3 1 0 .5 9 2 9 0 .0 7 total feces (g) 3 .0 7 5 2 .4 8 9 7 2 .2 9 4 6 4 .6 9 2 3 .7 7 8 9 3 .4 1 0 6 3 .5 7 5 4 2 .8 7 8 1 2 .7 5 8 9 average w eight days (g) 1 2 3 .6 8 7 .2 5 2 2 8 8 .5 5 1 2 2 .4 5 8 6 .5 5 8 8 .2 1 2 1 .6 5 2 3 3 3 2 8 6 .5 5 8 8 .0 5 2 2 6 7 ,8 9 ,1 0 6 7 ,8 9 ,1 0 6 7 ,8 9 ,1 0 1 :2 -4 1 :2 -5 1 :2 -6 2 :2 -4 2 :2 -5 2 :2 -6 3 :2 -4 3 :2 -5 3 :2 -6 6 .7 6 9.11 3 .1 9 6.91 6 .9 0 3.61 7 .6 8 6 .6 3 2 .5 6 1 9 0 .3 7 2 3 6 .1 9 7 3 .7 3 1 6 1 .5 5 1 8 6 .4 0 5 5 .6 6 157.11 1 8 0 .7 8 6 9 .0 7 1 .7 5 0 .0 2 0 .6 5 1 .4 5 1 .8 4 0 .4 3 1 .3 7 1 .8 3 0 .5 6 2 3 0 .0 5 2 6 1 .5 9 6 9 .1 4 1 7 3 .5 0 2 2 4 .0 2 4 6 .9 8 1 8 3 .6 8 2 1 2 .1 8 7 2 .4 7 2 1 .5 2 3 4 .2 1 7 .0 4 1 8 .0 7 2 6 .3 9 5 .3 5 1 9 .1 6 2 3 .0 9 7 .7 1 1 .0 6 1 .7 3 0 .4 7 0 .9 4 1 .3 3 0 .4 3 1 .0 2 1 .2 0 0 .5 7 3 .4 0 3 .7 9 0 .7 9 2 .1 5 3 .2 4 0 .5 0 2 .4 2 2 .9 3 0 .8 7 4 5 4 .9 2 5 4 6 .6 4 155.01 3 6 4 .5 8 4 5 0 .1 2 1 1 2 .9 7 3 7 2 .4 5 4 2 8 .6 5 1 5 3 .8 0 2 .7 6 1 9 4 .0 5 8 1 2 .0 9 3 5 4 .0 7 5 6 .3 7 1 3 .4 0 7 4 2 .9 2 7 9 4 .3 9 8 5 2 .4 5 7 5 9 4 .5 5 1 2 6 .6 8 2 .2 9 4 .2 5 1 2 6 .4 5 82.1 94 1 2 6 .6 8 1 .8 5 2 2 2 3 3 3 2 2 2 1 1 ,1 2 ,1 3 15 1 4 ,1 6 ,1 7 1 1 ,1 2 ,1 3 15 1 4 ,1 6 ,1 7 1 1 ,1 2 ,1 3 15 1 4 ,1 6 ,1 7 1 :3 -7 1 :3 -8 1 :3 -9 2 :3 -7 2 :3 -8 2 :3 -9 3 :3 -7 3 :3 -8 3 :3 -9 4 .0 0 4 .6 5 4 .7 3 3 .6 5 5 .6 9 4 .4 4 3 .3 0 4 .3 2 5 .5 2 8 7 .1 6 1 2 3 .0 4 1 3 6 .8 9 8 3 .1 8 1 3 8 .5 3 1 1 1 .1 5 7 5 .3 2 1 0 3 .3 0 150.11 0 .7 6 1 .1 7 1 .2 9 0 .6 7 1 .2 5 1 .0 0 0 .5 6 0 .9 7 1 .0 7 8 1 .7 9 1 3 9 .9 5 1 7 1 .9 7 7 8 .9 6 1 4 4 .5 0 1 1 3 .6 3 7 2 .1 2 1 0 0 .6 3 1 7 2 .0 6 8 .1 3 1 3 .2 7 1 5 .8 7 7 .8 8 15.61 1 0 .9 8 7 .6 5 1 0 .7 5 19.51 0 .5 4 0 .8 1 1 .0 9 0 .5 6 0 .9 4 0 .7 7 0 .4 9 0 .6 0 1 .2 4 1 .0 0 1 .8 9 2.41 0.91 1 .7 7 1 .1 5 0 .9 3 1 .1 9 2 .2 4 1 8 3 .3 8 2 8 4 .7 7 3 3 4 .2 6 1 7 5 .8 0 3 0 8 .2 9 2 4 3 .1 2 1 6 0 .3 6 2 2 1 .7 6 3 5 1 .7 6 3 .4 5 9 7 2 .2 9 9 4 2 .3 4 5 4 5 .8 1 4 7 3 .7 7 1 8 3 .7 7 2 7 4 .0 2 5 2 .5 2 6 5 2 .6 9 0 5 118 8 3 .5 5 8 2 .8 1 1 8 .7 5 8 3 .5 8 3 .0 5 1 1 9 .6 8 4 .2 8 3 .4 5 2 2 2 3 3 3 2 2 2 18 19 2 0 ,2 1 18 19 2 0 ,2 1 18 19 2 0 ,2 1 1 :4 -1 0 1 :4 -1 1 1 :4 -1 2 2 :4 -1 0 2 :4 -1 1 2 :4 -1 2 3 :4 -1 0 3 :4 -1 1 3 :4 -1 2 5.91 4 .2 3 5 .5 2 5 .2 3 5 .1 2 5 .5 8 4 .8 7 7 .8 3 5 .6 2 1 6 2 .5 8 1 0 7 .9 6 150.11 152.71 1 3 3 .5 3 1 3 5 .0 5 1 3 2 .3 9 146.11 1 6 6 .5 5 1 .2 3 0 .8 9 1 .0 7 1 .1 6 1 .1 2 1 .0 3 1 .0 5 1 .2 7 1.41 1 7 7 .1 7 1 1 2 .7 9 1 7 2 .0 6 1 7 4 .9 4 1 4 0 .4 3 1 3 0 .5 8 1 5 1 .4 9 1 7 6 .3 5 2 1 2 .1 4 1 6 .9 0 1 0 .8 6 19.51 1 6 .1 7 1 4 .0 9 1 4 .9 8 1 3 .4 6 16.41 2 0 .6 3 1 .0 0 0 .6 7 1 .2 4 1 .0 5 0 .9 5 1 .0 5 0 .8 8 0 .9 2 1 .3 2 2 .2 7 1 .3 8 2 .2 4 2 .1 6 1 .5 9 1 .3 6 1 .8 0 2 .3 9 2 .8 5 3 6 7 .0 6 2 3 8 .7 8 3 5 1 .7 6 3 5 3 .4 4 2 9 6 .8 4 2 8 9 .6 3 3 0 5 .9 4 3 5 1 .2 8 4 1 0 .5 1 1 .6 8 9 3 .1 4 3 2 3 .2 5 4 5 2 .7 1 3 3 4 .6 4 0 7 5 .2 0 7 5 2 .0 4 1 3 .4 4 6 4 3 .9 5 4 9 5 9 .5 1 1 6 .4 1 1 2 .2 5 8 .8 5 1 1 6 .5 5 1 1 1 .8 5 5 8 .7 1 1 7 .4 5 1 1 2 .9 2 2 2 3 3 3 2 2 2 22 2 4 ,2 5 2 3 ,2 6 ,2 7 22 2 4 ,2 5 2 3 ,2 6 ,2 7 22 2 4 ,2 5 2 3 ,2 6 ,2 7 1 :5 -1 3 1 :5 -1 4 1 :5 -1 5 2 :5 -1 3 2 :5 -1 4 2 :5 -1 5 3 :5 -1 3 3 :5 -1 4 3 :5 -1 5 4 .9 9 7 .8 4 3 .8 7 5 .8 3 7 .5 8 3 .6 5 6 .7 3 8 .4 9 2 .5 6 1 2 9 .3 4 2 0 9 .9 5 9 1 .6 5 1 4 9 .2 8 2 0 0 .3 1 5 9 .2 4 1 5 4 .4 0 2 0 8 .7 9 5 9 .2 8 1 .0 0 2 .0 4 0 .7 7 1 .2 7 1 .9 7 0 .4 7 1 .3 5 2 .0 5 0 .4 4 1 4 0 .4 1 2 4 4 .5 4 8 8 .5 2 1 5 2 .2 9 2 1 8 .4 9 4 4 .3 7 1 8 7 .1 1 2 0 4 .2 2 5 7 .2 3 13.41 3 0 .4 7 8 .0 3 1 6 .0 3 2 7 .9 7 4 .9 9 1 9 .7 5 2 5 .1 4 6 .1 5 0 .9 7 1 .4 6 0 .4 6 0 .8 6 1.31 0 .3 2 1 .0 2 1 .3 3 0 .4 3 1 .6 8 3 .6 5 0 .9 6 1 .7 9 2 .7 6 0 .4 8 2 .6 4 2 .4 0 0 .6 5 2 9 1 .8 1 4 9 9 .9 6 1 9 4 .2 7 3 2 7 .3 5 4 6 0 .3 8 1 1 3 .5 3 3 7 3 .0 1 4 5 2 .4 2 1 2 6 .7 3 3 .1 9 5 2 .9 4 0 8 2 .6 3 9 9 4 .9 7 1 2 4 .4 8 3 3 3 .7 6 7 3 .6 1 1 3 3 .3 5 2 2 2 .7 0 3 4 1 1 0 .7 8 8 .3 5 8 4 .6 1 1 1 .6 8 8 .5 8 5 .5 5 1 1 2 .8 5 8 8 .9 8 5 .5 2 2 2 3 3 3 2 2 2 2 8 ,2 9 31 3 0 ,3 2 2 8 ,2 9 31 3 0 ,3 2 2 8 ,2 9 31 3 0 ,3 2 1 :6 -1 6 1 :6 -1 7 1 :6 -1 8 2 :6 -1 6 2 :6 -1 7 2 :6 -1 8 3 :6 -1 6 3 :6 -1 7 3 :6 -1 8 4 .6 9 4.11 4.21 4 .5 0 3 .7 0 4 .0 6 4 .8 6 3 .7 2 4 .4 7 1 3 5 .9 2 1 0 9 .7 4 1 1 3 .7 6 1 2 0 .7 7 7 1 .6 4 9 5 .0 2 1 4 2 .3 8 8 6 .6 7 1 2 7 .1 7 1 .0 8 0 .9 3 0 .9 3 0 .9 2 0 .4 4 0 .7 3 1 .1 5 0 .6 0 0 .8 6 1 5 7 .5 4 1 1 5 .4 0 1 2 6 .1 8 1 2 5 .3 2 5 9 .2 7 8 4 .1 7 1 7 1 .5 9 7 8 .6 5 1 3 8 .1 8 1 4 .9 6 1 0 .9 6 1 3 .0 9 1 2 .4 4 6 .0 8 9 .2 6 1 6 .9 8 8 .8 4 14.41 0 .9 4 0 .6 6 0 .7 9 0 .8 3 0 .4 1 0 .5 1 1.01 0 .6 1 0 .7 5 2 .0 9 1 .4 2 1 .6 4 1 .3 7 0 .6 5 0 .9 4 2 .2 0 0.81 1 .8 3 3 1 7 .2 1 2 4 3 .2 3 2 6 0 .5 9 2 6 6 .1 6 1 4 2 .2 0 1 9 4 .6 9 3 4 0 .1 7 1 7 9 .9 0 2 8 7 .6 8 2 .5 0 3 6 2 .7 0 8 3 2 .3 5 5 4 3 .9 6 8 4 3 .9 6 7 8 3 .5 6 6 6 2 .9 0 7 6 3 .2 4 4 9 2 .7 6 4 3 87.1 1 1 2 .8 8 5 .4 8 7 .1 5 1 1 2 .4 5 8 4 .5 5 8 7 .6 5 1 1 1 .9 5 8 4 .6 5 2 2 2 3 3 3 2 2 2 3 3 ,3 4 ,3 5 3 6 ,3 7 3 8 ,3 9 3 3 ,3 4 ,3 5 3 6 ,3 7 3 8 ,3 9 3 3 ,3 4 ,3 5 3 6 ,3 7 3 8 ,3 9 1 :7 -1 9 1 :7 -2 0 1 :7 -2 1 2 :7 -1 9 2 :7 -2 0 2 :7 -2 1 3 :7 -1 9 3 :7 -2 0 3 :7 -2 1 2 .4 4 2 .3 9 2 .7 2 3 .0 2 2 .6 6 2.81 3 .6 0 2 .4 0 2 .6 4 4 7 .8 3 4 6 .6 2 6 8 .9 7 6 6 .8 4 4 9 .2 1 6 9 .5 4 8 0 .6 6 5 1 .9 0 7 3 .8 2 0 .3 7 0 .3 2 0 .6 0 0 .4 9 0 .3 1 0 .4 9 0 .4 7 0 .3 4 0 .6 2 3 9 .7 9 3 8 .6 1 7 1 .9 0 5 9 .6 3 3 8 .2 6 6 4 .1 2 7 1 .4 1 4 5 .2 5 8 1 .7 8 4 .8 9 5 .1 1 8 .5 6 6 .1 3 4 .7 3 6 .6 4 6 .6 9 5 .5 0 7 .9 9 0 .3 9 0 .4 9 0 .7 4 0 .4 3 0 .4 0 0 .4 6 0 .4 1 0 .4 3 0 .5 8 0 .3 8 0 .3 9 0 .8 0 0 .5 7 0.41 0 .6 9 0 .7 0 0 .4 8 0 .9 9 9 6 .0 9 9 3 .9 2 1 5 4 .3 0 1 3 7 .0 9 9 5 .9 9 1 4 4 .7 5 1 6 3 .9 4 106.31 168.41 1 .9 6 9 7 2 .0 7 9 8 2 .6 7 0 5 3 .4 4 7 7 3 .2 6 4 6 4 .3 0 5 9 2 .5 1 1 7 2 .4 3 6 9 3 .4 1 0 7 8 1 .3 5 8 2 .2 5 1 0 1 .0 5 8 2 .3 5 8 2 .7 5 1 0 1 .9 5 8 3 .5 8 3 .3 5 1 0 3 .2 2 2 2 3 3 3 2 2 2 total fa tty acid excretion (pm ol/100 g r m ouse/day) 3 0 0 .2 0 4 1 6 .9 5 4 4 7 .2 4 2 6 6 .1 8 3 5 8 .1 9 4 2 0 .9 2 4 4 8 .1 5 5 1 6 .4 2 4 5 4 .4 4 4 0 3 .1 9 8 0 .0 9 6 6 4 .4 3 8 7 6 .1 2 1 9 7 .4 0 5 2 5 .4 3 7 5 5 .9 6 1 5 6 .2 9 5 8 0 .0 5 7 4 4 .6 3 2 3 0 .8 9 5 2 5 .6 9 2 6 8 .5 8 2 6 8 .8 3 3 9 1 .8 6 4 7 3 .4 1 2 8 6 .9 4 4 6 4 .2 0 3 6 8 .1 4 2 6 9 .8 3 3 3 2 .7 0 5 6 7 .0 5 3 8 0 .3 3 1 0 3 .9 7 5 2 0 .9 7 3 2 2 .3 9 5 1 0 .1 6 5 4 3 .1 8 3 9 3 .9 7 4 4 9 .4 8 5 3 1 .8 8 5 1 5 .3 9 7 1 9 .0 0 5 0 0 .7 1 1 1 0 .0 9 4 2 1 .1 1 8 3 2 .0 8 3 0 3 .1 0 4 8 6 .0 6 7 7 7 .4 1 1 6 6 .6 3 5 9 6 .8 3 8 5 2 .9 7 2 0 0 .3 5 5 1 5 .1 7 2 6 5 .8 1 4 5 5 .9 0 2 9 2 .0 0 3 5 9 .3 7 4 0 3 .9 9 1 6 7 .2 5 2 7 3 .7 6 5 6 4 .2 2 2 6 0 .7 2 4 6 9 .7 2 3 6 0 .7 7 1 2 4 .4 7 1 1 6 .3 3 1 1 8 .7 5 2 0 3 .8 9 1 9 1 .3 2 1 2 6 .2 3 2 0 3 .7 9 2 4 6 .5 6 1 5 5 .4 1 2 7 8 .3 0 1 8 2 .2 9 5 7 .6 8 % o f fatty acids 1 C 1 4 :0 C 1 6 :0 C16:1 C 1 8 :0 C 18:1 C 1 8 :2 C 18:3 2.94 50.65 0.44 4 1 .1 4 4.11 0 .2 3 0.5 0 2.20 48.43 0.40 4 4 .4 7 4.11 0 .2 7 0.1 2 2.05 46.53 0.42 4 5 .2 8 4.90 0.27 0.55 2.09 47.74 0.36 2.09 49.15 0.35 4 3 .8 7 4 3 .2 3 5 .0 4 4 .4 0 0 .3 5 0 .3 0 0 .5 5 0 .4 8 1.69 43 .7 0 0.42 1.47 37 .3 9 0.32 4 8 .3 3 5 3 .7 2 4 .9 0 5 .8 4 0 .3 2 0 .3 4 0 .6 4 0 .9 2 1.81 4 5 .9 6 0 .3 5 1.74 44 .4 6 0.35 4 6 .0 0 4 7 .7 3 5 .0 3 4 .7 7 0 .3 1 0 .3 1 0 .5 4 0 .6 5 2.01 4 6 .0 0 0.3 8 0 .4 2 3.91 0.0 4 4 5 .9 7 3 .6 5 4 .7 9 0 .5 4 0 .3 0 0 .0 4 0 .5 5 0.21 1.49 41 .8 5 0.39 5 0 .5 7 4.73 0.23 0.75 1.67 43.21 0.00 4 7 .8 5 6.26 0.32 0.69 2.06 47.57 0.42 1.90 44.31 0.40 4 4 .6 0 4 7 .5 9 4 .5 4 4 .9 6 0 .3 0 0 .2 6 0.51 0 .5 9 1.53 41.41 0.41 3.19 49.27 0.38 4 9 .7 7 4 1 .5 9 5 .8 6 4 .7 4 0 .3 0 0 .3 8 0 .7 2 0 .4 5 2.06 42.18 0.37 4 9 .3 2 5.14 0.28 0.65 1.55 42 .1 7 0.43 4 9 .5 0 5.39 0.28 0.68 1.66 44.91 0.36 4 7 .1 2 5.01 0 .3 7 0.5 6 1.90 44 .1 0 0.35 4 7 .5 4 5.18 0.30 0.62 0.53 2.74 0.13 2 .8 6 0.57 0.05 0.10 2 .1 8 4 7 .5 3 0.41 4 4 .6 0 4.43 0.30 0.54 1.63 43.21 0.41 1.42 40 .9 5 0.39 4 9 .1 4 5 1 .4 5 4 .6 6 4 .7 5 0 .2 8 0 .3 3 0 .6 6 0 .7 2 2 .0 8 47.31 0.38 1.85 4 4 .9 3 0.41 4 4 .9 1 4 6 .8 7 4 .4 8 5 .0 6 0 .3 2 0 .3 0 0 .5 2 0 .5 7 1.83 4 5 .7 2 0.41 4 6 .7 4 4.52 0.32 0.48 2.06 46.97 0.35 4 4 .9 7 4 .7 7 0.31 0.5 8 1.95 46 .5 8 0.44 1.57 4 2 .6 8 0.31 4 5 .3 8 4 8 .9 2 4 .8 5 5 .5 5 0 .2 7 0 .3 5 0 .5 3 0 .6 4 1.84 45 .1 0 0.39 0.26 2.33 0.04 4 7 .0 0 2 .3 7 4 .7 9 0 .3 5 0 .3 1 0 .0 2 0 .5 8 0 .0 8 1.61 4 4 .2 9 0 .3 4 1.77 45.21 0.37 4 8 .2 7 4 7 .2 4 4 .6 0 4 .5 5 0 .2 7 0 .2 8 0 .6 2 0 .5 8 1.57 4 2 .6 8 0.31 1.48 43.21 0.33 4 8 .9 2 4 9 .5 0 5 .5 5 4 .5 8 0 .3 5 0 .3 0 0 .6 4 0.61 1.73 44 .9 9 0.38 1.93 46 .6 3 0.36 4 7 .3 1 4 5 .0 9 4 .7 5 5 .1 7 0 .3 2 0 .3 6 0 .5 4 0 .4 7 1.59 43 .2 7 0.34 4 9 .5 2 4.40 0.29 0.59 2.23 41.59 0.36 5 0 .2 0 4.67 0.26 0.68 1.37 40 .5 7 0.34 5 1 .6 8 5.02 0.32 0.69 1.70 43 .6 0 0.35 4 8 .6 3 4.81 0.31 0.6 0 0 .2 6 1.89 0.02 1 .9 3 0.37 0.03 0.07 1.71 4 4 .3 2 0 .3 4 4 8 .1 2 4.60 0.33 0.58 1.57 4 1 .9 9 0.41 4 8 .9 1 6.09 0.29 0.73 1.99 47 .1 8 0.40 4 5 .5 6 4.13 0.24 0.50 1.78 45 .6 0 0.39 4 6 .5 2 4.90 0.26 0.55 1.65 43.51 0.43 4 7 .4 6 6.07 0.28 0.60 3.21 5 2 .1 8 0.4 2 3 9 .0 9 4.40 0.28 0.42 1.81 4 1 .3 9 0 .3 6 5 0 .1 6 5 .3 0 0 .2 7 0.71 1.88 46 .1 5 0.45 2.02 46.77 0.34 4 5 .1 4 4 5 .1 6 5 .5 6 4 .8 6 0 .2 9 0 .3 4 0 .5 3 0.51 1.96 45 .4 6 0.39 4 6 .2 4 5.10 0.29 0.57 0.49 3.24 0.04 3 .1 9 0.70 0.03 0.10 1.48 42 .8 5 0.34 4 9 .6 6 4.72 0.30 0.66 1.69 45 .1 2 0.38 4 7 .4 4 4.51 0 .2 7 0.5 9 1.62 43 .6 5 0.36 4 8 .4 2 5.02 0.30 0.63 1.69 45 .3 8 0.35 4 7 .0 8 4 .6 8 0.31 0.5 2 2 .6 0 5 0 .3 8 0.31 2 .0 9 48.81 0.37 4 1 .6 8 4 3 .2 3 4 .2 8 4 .7 6 0 .2 9 0 .2 6 0 .4 5 0 .4 8 1.43 41 .8 6 0.34 5 0 .4 4 4.99 0.30 0.65 2.07 48.18 0.33 1.55 44 .2 0 0.30 4 3 .7 2 4 8 .0 3 4 .9 1 5 .0 1 0 .3 4 0 .2 6 0 .4 5 0 .6 4 1.80 45 .6 0 0.34 4 6 .6 4 4.76 0.29 0.56 0.38 2.90 0.03 3 .0 5 0.25 0.03 0.09 2.54 49.77 0.38 4 1 .4 1 5.09 0.40 0.40 2.54 49.63 0.34 1.77 44 .7 0 0.39 4 1 .1 1 4 6 .6 0 5 .4 4 5 .5 5 0 .5 2 0 .4 8 0 .4 2 0 .5 2 2.20 48.75 0.36 4 3 .4 9 4.47 0.32 0.42 2.77 51.26 0.33 3 9 .8 6 4 .9 3 0.41 0.4 3 1.94 48 .0 4 0.34 4 4 .3 0 4.59 0.32 0.48 2.20 49.20 0.29 4 3 .5 6 4.08 0.25 0.43 2 .2 6 48.81 0.32 4 2 .5 7 5 .1 8 0.41 0.4 5 1.57 43 .8 3 0.37 4 8 .5 6 4.74 0.34 0.58 2.20 48.22 0.35 4 3 .4 9 4.90 0.38 0.46 0.39 2.42 0.03 2 .7 4 0.48 0.09 0.06 Appendix to TNO-report of 3M-02 Final version 04-12-2006 fatty acid total fatty acids C14:0 C16:0 C16:1 C18:0 C18:1 C18:2 C18:3 fatty acid total fatty acids C14:0 C16:0 C16:1 C18:0 C18:1 C18:2 C18:3 fatty acid total fatty acids C14:0 C16:0 C16:1 C18:0 C18:1 C18:2 C18:3 group 1 vs 2 nn p 9 9 0.258 9 9 0.297 9 9 0.136 9 9 0.666 9 9 0.191 9 9 0.222 9 9 0.931 9 9 0.190 group 2 vs 4 nn p 9 9 0.489 9 9 0.546 9 9 1.000 9 9 0.019 9 9 0.489 9 9 0.190 9 9 0.863 9 9 0.546 group 3 vs 7 nn p 9 9 <0.001 9 9 0.040 9 9 0.011 9 9 0.019 9 9 0.006 9 9 0.546 9 9 0.031 9 9 0.002 group 1 vs 3 nn p 9 9 0.730 9 9 0.436 9 9 0.340 9 9 0.730 9 9 0.297 9 9 0.863 9 9 0.666 9 9 0.666 group 2 vs 5 nn p 9 9 1.000 9 9 0.605 9 9 0.436 9 9 0.730 9 9 0.340 9 9 0.730 9 9 0.489 9 9 0.297 group 4 vs 5 nn p 9 9 1.000 9 9 0.113 9 9 0.161 9 9 0.019 9 9 0.094 9 9 0.387 9 9 0.297 9 9 0.340 fatty acid excretion, p values Mann-Whitney U-test group 1 vs 4 group 1 vs 5 group 1 vs 6 nn E nn p nn p 9 9 0.040 9 9 0.387 9 9 0.546 9 9 0.094 9 9 0.436 9 9 0.190 9 9 0.050 9 9 0.436 9 9 0.489 9 9 0.136 9 9 0.605 9 9 0.077 9 9 0.050 9 9 0.546 9 9 0.546 9 9 0.931 9 9 0.387 9 9 0.863 9 9 0.863 9 9 0.387 9 9 0.387 9 9 0.387 9 9 0.863 9 9 1.000 group 2 vs 6 group 2 vs 7 group 3 vs 4 nn p nn p nn p 9 9 0.222 9 9 0.008 9 9 0.040 9 9 0.931 9 9 0.063 9 9 0.222 9 9 0.222 9 9 0.008 9 9 0.190 9 9 0.014 9 9 0.040 9 9 0.014 9 9 0.546 9 9 0.008 9 9 0.077 9 9 0.094 9 9 0.436 9 9 1.000 9 9 0.796 9 9 0.024 9 9 0.730 9 9 0.190 9 9 0.001 9 9 0.436 group 4 vs 6 group 4 vs 7 group 5 vs 6 nn p nn p nn p 9 9 0.040 9 9 <0.001 9 9 0.222 9 9 0.730 9 9 0.011 9 9 0.340 9 9 0.161 9 9 0.002 9 9 1.000 9 9 0.730 9 9 1.000 9 9 0.011 9 9 0.222 9 9 0.001 9 9 0.863 9 9 0.931 9 9 0.605 9 9 0.489 9 9 0.436 9 9 0.040 9 9 0.546 9 9 0.489 9 9 <0.001 9 9 1.000 group 1 vs 7 nn p 9 9 <0.001 9 9 0.222 9 9 0.136 9 9 0.136 9 9 0.136 9 9 0.605 9 9 0.019 9 9 0.031 group 3 vs 5 nn p 9 9 0.297 9 9 0.931 9 9 0.931 9 9 0.863 9 9 1.000 9 9 0.340 9 9 0.136 9 9 0.796 group 5 vs 7 nn p 9 9 0.004 9 9 0.136 9 9 0.050 9 9 0.019 9 9 0.063 9 9 0.605 9 9 0.011 9 9 0.014 group 2 vs 3 nn p 9 9 0.297 9 9 0.730 9 9 0.387 9 9 0.730 9 9 0.387 9 9 0.113 9 9 0.546 9 9 0.340 group 3 vs 6 nn p 9 9 0.730 9 9 0.666 9 9 0.796 9 9 0.008 9 9 1.000 9 9 0.863 9 9 0.161 9 9 0.666 group 6 vs 7 nn p 9 9 0.002 9 9 0.040 9 9 0.077 9 9 0.796 9 9 0.050 9 9 0.489 9 9 0.008 9 9 0.008 p<005 Page A119 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Fatty acid balance group 1 1 1 1 1 1 1 1 1 AVERAGE SD 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 4 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 AVERAGE SD cage# 1,2 3,4 5 1,2 3,4 5 1,2 3,4 5 GC sam ple# 1:1-1 1:1 -2 1:1-3 2:1-1 2:1-2 2:1-3 3:1-1 3:1-2 3:1-3 6 7,8 9,10 6 7,8 9,10 6 7,8 9,10 1:2-4 1:2-5 1:2 -6 2:2-4 2:2-5 2:2-6 3:2-4 3:2-5 3:2-6 1 1 ,1 2 ,1 3 15 1 4 ,1 6 ,1 7 1 1 ,1 2 ,1 3 15 1 4 ,1 6 ,1 7 1 1 ,1 2 ,1 3 15 1 4 ,1 6 ,1 7 1:3-7 1:3-8 1:3-9 2:3-7 2:3-8 2:3-9 3:3-7 3:3-8 3:3-9 18 19 20,21 18 19 20,21 18 19 20,21 1:4-10 1:4-11 1:4-12 2 :4 -1 0 2:4-11 2 :4 -1 2 3 :4 -1 0 3:4-11 3 :4 -1 2 22 2 4 ,2 5 2 3 ,2 6 ,2 7 22 2 4 ,2 5 2 3 ,2 6 ,2 7 22 2 4 ,2 5 2 3 ,2 6 ,2 7 1:5-13 1:5-14 1:5-15 2 :5 -1 3 2 :5 -1 4 2 :5 -1 5 3 :5 -1 3 3 :5 -1 4 3 :5 -1 5 2 8 ,2 9 31 3 0 ,3 2 2 8 ,2 9 31 3 0 ,3 2 2 8 ,2 9 31 3 0 ,3 2 1:6-16 1:6-17 1:6-18 2 :6 -1 6 2 :6 -1 7 2 :6 -1 8 3 :6 -1 6 3 :6 -1 7 3 :6 -1 8 3 3 ,3 4 ,3 5 3 6 ,3 7 3 8 ,3 9 3 3 ,3 4 ,3 5 3 6 ,3 7 3 8 ,3 9 3 3 ,3 4 ,3 5 3 6 ,3 7 3 8 ,3 9 1:7-19 1:7-20 1:7-21 2 :7 -1 9 2 :7 -2 0 2:7-21 3 :7 -1 9 3 :7 -2 0 3:7-21 total fatty acids (pm ol/g feces) 2 4 1 .3 3 2 9 2 .2 4 3 4 5 .1 8 2 0 8 .4 0 246.11 3 2 6 .5 6 3 0 4 .9 6 3 1 0 .5 9 2 9 0 .0 7 4 5 4 .9 2 5 4 6 .6 4 155.01 3 6 4 .5 8 4 5 0 .1 2 1 1 2 .9 7 3 7 2 .4 5 4 2 8 .6 5 1 5 3 .8 0 1 8 3 .3 8 2 8 4 .7 7 3 3 4 .2 6 1 7 5 .8 0 3 0 8 .2 9 2 4 3 .1 2 1 6 0 .3 6 2 2 1 .7 6 3 5 1 .7 6 3 6 7 .0 6 2 3 8 .7 8 3 5 1 .7 6 3 5 3 .4 4 2 9 6 .8 4 2 8 9 .6 3 3 0 5 .9 4 3 5 1 .2 8 410.51 291.81 4 9 9 .9 6 1 9 4 .2 7 3 2 7 .3 5 4 6 0 .3 8 1 1 3 .5 3 373.01 4 5 2 .4 2 1 2 6 .7 3 317.21 2 4 3 .2 3 2 6 0 .5 9 2 6 6 .1 6 1 4 2 .2 0 1 9 4 .6 9 3 4 0 .1 7 1 7 9 .9 0 2 8 7 .6 8 9 6 .0 9 9 3 .9 2 1 5 4 .3 0 1 3 7 .0 9 9 5 .9 9 1 4 4 .7 5 1 6 3 .9 4 106.31 168.41 total feces (g) 3 .0 7 5 2.4 8 9 7 2.2 9 4 6 4 .6 9 2 3.7 7 8 9 3.4 1 0 6 3.5 7 5 4 2.8781 2.7 5 8 9 2.7 6 1 9 4.0581 2.0 9 3 5 4 .0 7 5 6.371 3.4 0 7 4 2.9 2 7 9 4.3 9 8 5 2.4 5 7 5 3.4 5 9 7 2.2 9 9 4 2.3 4 5 4 5.8 1 4 7 3.7 7 1 8 3.7 7 2 7 4 .0 2 5 2.5 2 6 5 2.6 9 0 5 1 .6 8 9 3.1 4 3 2 3.2 5 4 5 2.7 1 3 3 4.6 4 0 7 5.2 0 7 5 2.041 3.4 4 6 4 3.9 5 4 9 3 .1 9 5 2.9 4 0 8 2.6 3 9 9 4.9 7 1 2 4.4 8 3 3 3 .7 6 7 3.6 1 1 3 3.3 5 2 2 2.7 0 3 4 2.5 0 3 6 2.7 0 8 3 2.3 5 5 4 3.9 6 8 4 3.9 6 7 8 3.5 6 6 6 2.9 0 7 6 3.2 4 4 9 2.7 6 4 3 1 .9 6 9 7 2.0 7 9 8 2.6 7 0 5 3.4 4 7 7 3.2 6 4 6 4.3 0 5 9 2.5 1 1 7 2.4 3 6 9 3.4 1 0 7 average weight (g) 1 2 3 .6 8 7 .2 5 8 8 .5 5 1 2 2 .4 5 8 6 .5 5 88.2 1 2 1 .6 5 8 6 .5 5 8 8 .0 5 days 2 2 2 3 3 3 2 2 2 9 4 .5 5 1 2 6 .6 82.2 9 4 .2 5 1 2 6 .4 5 82.1 94 1 2 6 .6 8 1 .8 5 2 2 2 3 3 3 2 2 2 118 8 3 .5 5 82.8 1 1 8 .7 5 83.5 8 3 .0 5 1 1 9 .6 84.2 8 3 .4 5 2 2 2 3 3 3 2 2 2 59.5 1 1 6 .4 112.2 5 8 .8 5 1 1 6 .5 5 1 1 1 .8 5 58.7 1 1 7 .4 5 1 1 2 .9 2 2 2 3 3 3 2 2 2 1 1 0 .7 8 8 .3 5 84.6 111.6 88.5 8 5 .5 5 1 1 2 .8 5 88.9 85.5 2 2 2 3 3 3 2 2 2 87.1 112.8 85.4 8 7 .1 5 1 1 2 .4 5 8 4 .5 5 8 7 .6 5 1 1 1 .9 5 8 4 .6 5 2 2 2 3 3 3 2 2 2 8 1 .3 5 8 2 .2 5 1 0 1 .0 5 8 2 .3 5 8 2 .7 5 1 0 1 .9 5 83.5 8 3 .3 5 1 0 3 .2 2 2 2 3 3 3 2 2 2 fatty acids excretion (pm ol/100 gr m ouse/day) 3 0 0 .2 0 4 1 6 .9 5 4 4 7 .2 4 2 6 6 .1 8 3 5 8 .1 9 4 2 0 .9 2 4 4 8 .1 5 5 1 6 .4 2 4 5 4 .4 4 4 0 3 .1 9 8 0 .0 9 6 6 4 .4 3 8 7 6 .1 2 1 9 7 .4 0 5 2 5 .4 3 7 5 5 .9 6 1 5 6 .2 9 5 8 0 .0 5 7 4 4 .6 3 2 3 0 .8 9 5 2 5 .6 9 2 6 8 .5 8 2 6 8 .8 3 3 9 1 .8 6 473.41 2 8 6 .9 4 4 6 4 .2 0 3 6 8 .1 4 2 6 9 .8 3 3 3 2 .7 0 5 6 7 .0 5 3 8 0 .3 3 1 0 3 .9 7 5 2 0 .9 7 3 2 2 .3 9 5 1 0 .1 6 5 4 3 .1 8 3 9 3 .9 7 4 4 9 .4 8 5 3 1 .8 8 5 1 5 .3 9 7 1 9 .0 0 500.71 1 1 0 .0 9 421.11 8 3 2 .0 8 3 0 3 .1 0 4 8 6 .0 6 777.41 1 6 6 .6 3 5 9 6 .8 3 8 5 2 .9 7 2 0 0 .3 5 5 1 5 .1 7 265.81 4 5 5 .9 0 2 9 2 .0 0 3 5 9 .3 7 4 0 3 .9 9 1 6 7 .2 5 2 7 3 .7 6 5 6 4 .2 2 2 6 0 .7 2 4 6 9 .7 2 3 6 0 .7 7 1 2 4 .4 7 1 1 6 .3 3 1 1 8 .7 5 2 0 3 .8 9 1 9 1 .3 2 1 2 6 .2 3 2 0 3 .7 9 2 4 6 .5 6 155.41 2 7 8 .3 0 1 8 2 .2 9 5 7 .6 8 fo o d intake (g) 23.2 18 16.8 36.8 28.8 25.6 20.2 15.3 13.8 19.9 27.7 16.3 28.8 45.4 28.2 16.7 23.6 13.2 26.2 16.5 18.3 44.7 28.3 29.3 23.7 13.6 14.7 12 21.7 24 19.8 35.2 38.2 11.3 18.7 22.6 21.5 19.6 19.5 36.5 32.2 30.3 18.7 28 14.5 17.6 20.3 17.2 29.7 31 27.9 16.5 17.1 15 16.8 16.9 21.9 29.2 26.5 35 15.7 15 19.8 fa tty a c id s uptake (pm ol/100 gr m ouse/day) 5 2 8 3 .2 2 5 8 0 6 .7 9 5340.11 5 6 3 9 .3 2 6244.01 5 4 4 6 .4 0 4 6 7 3 .7 8 4 9 7 5 .6 9 4 4 1 1 .4 3 5 9 2 4 .0 8 6158.51 5 5 8 1 .4 2 5 7 3 3 .8 9 6 7 3 7 .1 3 6445.31 5 0 0 0 .5 5 5 2 4 6 .9 6 4 5 3 9 .2 5 6 2 4 9 .5 5 5 5 5 8 .6 2 6 2 2 0 .8 5 7 0 6 3 .3 7 6 3 5 9 .7 2 6 6 2 0 .1 2 5 5 7 7 .5 9 4 5 4 6 .2 8 4 9 5 8 .1 6 5 6 7 6 .6 7 5 2 4 7 .3 0 6020.71 6 3 1 3 .3 0 5 6 6 7 .2 0 6 4 0 8 .6 3 5 4 1 8 .3 8 4 4 8 1 .4 4 5 6 3 4 .3 5 5 4 6 6 .6 4 6 2 4 4 .2 3 6 4 8 7 .7 4 6 1 3 7 .1 5 6 8 2 7 .3 3 6 6 4 6 .0 0 4 6 6 4 .1 2 8 8 6 5 .1 4 4 7 7 3 .4 4 5 6 8 7 .5 3 5 0 6 5 .4 3 5668.91 6 3 9 4 .8 0 5 1 7 2 .9 7 6 1 9 1 .9 7 5 2 9 8 .6 0 4 2 9 9 .3 3 4 9 8 7 .6 2 5 8 1 2 .7 4 5 7 8 3 .3 6 6 1 0 0 .1 0 6653.61 6 0 0 9 .1 9 6 4 4 1 .9 7 5 2 9 2 .2 8 5065.41 5 4 0 0 .2 6 ch o le ste ro l balance (pm ol/100 gr mouse/day) 4 9 8 3 .0 2 5 3 8 9 .8 4 4 8 9 2 .8 7 5 3 7 3 .1 5 5 8 8 5 .8 2 5 0 2 5 .4 8 4 2 2 5 .6 4 4 4 5 9 .2 7 3 9 5 6 .9 8 4 9 1 0 .2 3 6 1 1 .9 3 5 2 5 9 .6 5 5 2 8 2 .3 9 5 3 8 4 .0 3 5 2 0 8 .4 5 5 9 8 1 .1 7 6 2 8 9 .0 3 4 4 2 0 .5 0 4 5 0 2 .3 3 4 3 0 8 .3 6 5 1 8 1 .7 7 6 8 2 .5 4 5 9 8 0 .7 1 5 1 6 6 .7 6 5 7 4 7 .4 5 6 7 7 6 .4 3 5 8 9 5 .5 2 6 2 5 1 .9 8 5 3 0 7 .7 6 4 2 1 3 .5 7 4 3 9 1 .1 1 5 5 2 5 .7 0 8 4 1 .8 8 5 1 5 5 .7 0 4 9 2 4 .9 1 5 5 1 0 .5 5 5 7 7 0 .1 3 5 2 7 3 .2 2 5 9 5 9 .1 5 4 8 8 6 .5 1 3 9 6 6 .0 5 4 9 1 5 .3 4 5 1 5 1 .2 8 587.51 5 0 4 5 .5 2 5 4 1 2 .1 5 6 1 8 4 .6 4 5 6 5 1 .0 9 6 0 4 9 .9 2 6 4 7 9 .3 8 4 0 6 7 .2 9 8 0 1 2 .1 6 4 5 7 3 .0 8 5 7 1 9 .4 7 1 1 5 9 .5 6 5 2 3 1 .6 3 4 7 7 3 .4 3 5 3 0 9 .5 4 5 9 9 0 .8 1 5 0 0 5 .7 2 5 9 1 8 .2 1 4 7 3 4 .3 8 4 0 3 8 .6 2 4 5 1 7 .9 0 5 0 5 7 .8 1 6 3 4 .7 0 5 6 9 6 .4 2 5 6 6 4 .6 1 5 8 9 6 .2 1 6 4 6 2 .2 9 5 8 8 2 .9 6 6 2 3 8 .1 8 5 0 4 5 .7 1 4 9 1 0 .0 0 5 1 2 1 .9 6 5 6 5 7 .5 9 5 3 7 .8 3 m olw C 14:0 C 16:0 C 1 6 :1 C 18:0 C 1 8 :1 C 18:2 C 18:3 average 2 2 8 .4 2 5 6 .4 2 5 4 .4 2 8 4 .5 2 8 2 .5 2 8 0 .5 2 7 8 .5 M Y S TR IC A C ID P A LM ITIC A C ID P A LM IT O LE IC AC ID S T E A R IC A C ID O LE IC AC ID LIN O LE IC AC ID LIN O LE N IC AC ID 266.46 g/mol diet: 15 % fat= 0 .5 6 3 m m ol per g diet Page A120 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 fatty acid balance balance fatty acid balance balance fatty acid balance balance fatty acid balance, p values Mann-Whitney U-test group 1 vs 2 I group 1 vs 3 group 1 vs 4 group 1 vs 5 I group 1 vs 6 nn E nn p nn p nn p nn p 9 9 0.436 9 9 0.113 9 0.489 9 9 0.063 9 SH 0.730 group 2 vs 4 group 2 vs 5 group 2 vs 6 group 2 vs 7 group 3 vs 4 nn n n p__ I n n p n n p__ I n n p 9 9 0.8631 9 91 0.258 I 9 9 0.7961 9 9 l 0.258 I 9 9 0.222 group 3 vs 7 group 4 vs 5 group 4 vs 6 group 4 vs 7 group 5 vs 6 n n p nn p_ n n p n n p__ n n p 9 9 1.0001 9 9 l 0.222 9 9 0.730| 9 9 l 0.136 9 9 0.136 group 1 vs 7 group 2 vs 3 nn nn p r~9~ 9 0.019 9 9 0.546 group 3 vs 5 group 3 vs 6 rsn n p__ I n r 9 l 91 0.863 I ni 9] p__ I 0.297 I group 5 vs 7 group 6 vs 7 n n p nn p_ 9 9 0.931| 9 9 l 0.094 p<0.05 Page A121 of A172 Appendix to TNO-report of 3M-02 Final version Appendix F. Intestinal cholesterol absorption C holesterol absorption O ral g a v a g e m ix: 14 C dpm average: 7 6 0 8 3 .3 7 6 5 4 7 .5 7 5 2 0 5 .8 7 4 1 7 4 .5 7 3 7 6 3 .5 7 5 6 6 9 .7 1 75241 I 3H dpm average: 92065.2 92196.7 90472.4 88575.4 92526.8 92548.9 91398 | 14C /3H dosing: 1 0.8231 Mouse# 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 14C dpm feces 7900.00 9070.58 8759.79 7943.46 9442.29 9027.49 9996.01 10914.90 11495.20 8402.11 8966.49 9560.47 10754.70 11858.50 12382.30 8918.47 9795.44 9570.76 11342.40 10247.10 11420.10 10160.50 11533.30 11375.70 9360.62 9242.62 9409.35 10257.10 11572.10 11790.60 7215.69 6854.01 8420.46 7620.85 7592.86 7701.77 10718.20 9765.43 11045.10 8973.56 10118.90 10186.80 11415.30 11521.70 9926.39 9713.21 10522.10 10357.80 10622.10 10309.40 9363.58 9289.29 8492.80 9169.78 7720.92 8438.85 8631.31 10252.90 9662.34 10 5 8 9 .0 0 3H dpm feces 17857.0 20224.1 19669.7 AVERAGE 17369.9 20044.0 19314.7 AVERAGE 16226.5 17696.9 19154.0 AVERAGE 15319.6 16793.3 16635.3 AVERAGE 19111.4 20818.2 21352.2 AVERAGE 19316.9 21221.6 20766.7 AVERAGE 19935.8 17921.2 19737.7 AVERAGE 22122.3 24951.5 24849.9 AVERAGE 18676.0 18523.6 18338.6 AVERAGE 18752.4 20953.2 21592.7 AVERAGE 13209.8 12708.1 14817.4 AVERAGE 13562.2 13608.7 13685.9 AVERAGE 22219.9 20159.2 22642.2 AVERAGE 15531.3 17347.9 17603.2 AVERAGE 21059.0 21372.1 19181.1 AVERAGE 17538.7 18995.2 18714.0 AVERAGE 17065.5 16759.2 15186.6 AVERAGE 18158.2 16878.2 18096.8 AVERAGE 15528.4 17238.0 17527.6 AVERAGE 18655.8 17086.2 19019.0 A V E RAGE 14/3H feces 0.442 0.449 0.445 0.445 0.457 0.471 0.467 0.465 0.616 0.617 0.600 0.611 0.548 0.534 0.575 0.552 0.563 0.570 0.580 0.571 0.462 0.462 0.461 0.461 0.569 0.572 0.579 0.573 0.459 0.462 0.458 0.460 0.501 0.499 0.513 0.504 0.547 0.552 0.546 0.548 0.546 0.539 0.568 0.551 0.562 0.558 0.563 0.561 0.482 0.484 0.488 0.485 0.578 0.583 0.579 0.580 0.542 0.539 0.518 0.533 0.554 0.554 0.553 0.554 0.622 0.615 0.617 0.618 0.512 0.503 0.507 0.507 0.497 0.490 0.492 0.493 0.550 0.566 0.557 0.557 % cholesterol absorption 45.89 43.48 25.78 32.90 30.67 43.95 30.38 44.15 38.73 33.38 33.03 31.87 41.10 29.56 35.27 32.73 24.92 38.39 40.11 32.30 04-12-2006 Page A122 of A172 Appendix to TNO-report of 3M-02 Final version Mouse# 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 14C dpm feces 8632.76 7757.78 8732.12 9317.58 10349.10 10995.40 12726.80 11922.70 10824.40 11803.80 11509.60 10446.20 9824.33 10536.10 10819.00 9944.17 9896.95 9024.08 11012.10 12345.10 12611.60 10539.20 11997.90 11733.20 8467.17 8615.23 7791.76 10611.20 11669.60 11704.20 6797.41 8479.36 8042.25 9667.22 10332.00 10290.40 9274.67 9043.46 8359.95 8337.87 8978.72 9290.98 9260.73 8926.69 8216.57 7388.65 7801.01 8272.11 8775.47 8627.50 7935.44 8265.72 7672.71 7372.15 6512.96 7565.00 7444.81 8569.40 9540.76 9523.59 8330.02 9412.73 9427.18 9607.51 9889.25 9677.26 10990.90 9651.99 11648.90 9120.82 10887.20 11023.60 7559.63 8832.90 9369.62 3H dpm feces 18263.4 16543.7 18151.9 AVERAGE 18797.2 20750.2 21398.2 AVERAGE 21922.9 20859.7 19073.0 AVERAGE 20531.4 19930.8 17926.4 AVERAGE 17823.8 19638.0 19717.7 AVERAGE 17861.6 17830.0 16251.3 AVERAGE 20530.5 22826.4 23740.9 AVERAGE 19138.3 21840.1 21335.4 AVERAGE 19713.7 19837.0 18343.0 AVERAGE 16118.3 17565.2 17995.9 AVERAGE 15090.2 18363.5 17655.2 AVERAGE 18299.0 19525.1 19416.7 AVERAGE 18965.3 18555.8 17064.5 AVERAGE 16938.5 18142.5 18500.1 AVERAGE 21618.5 20655.8 19301.2 AVERAGE 17101.3 18082.3 19128.3 AVERAGE 18331.8 18170.1 16944.8 AVERAGE 17166.9 16099.9 15533.3 AVERAGE 13424.4 15510.5 15298.9 AVERAGE 17514.8 19514.6 19814.4 AVERAGE 16006.8 17737.5 17550.5 AVERAGE 19624.7 19941.0 19580.0 AVERAGE 20009.6 17422.8 20445.0 AVERAGE 17747.4 20878.9 21294.1 AVERAGE 14314.6 16604.8 17203. 4 AVERAGE 14/3H feces 0.473 0.469 0 .4 8 1 0.474 0.496 0.499 0.514 0.503 0 .5 8 1 0.572 0.568 0.573 0.575 0.577 0.583 0.578 0 .5 5 1 0.537 0.549 0.545 0.557 0.555 0.555 0.556 0.536 0 .5 4 1 0 .5 3 1 0.536 0 .5 5 1 0.549 0.550 0.550 0.430 0.434 0.425 0.430 0.658 0.664 0.650 0.658 0.450 0.462 0.456 0.456 0.528 0.529 0.530 0.529 0.489 0.487 0.490 0.489 0.492 0.495 0.502 0.496 0.428 0.432 0.426 0.429 0.432 0 .4 3 1 0.432 0.432 0.479 0.475 0.468 0.474 0 .4 8 1 0.477 0.475 0.478 0.485 0.488 0.487 0.487 0.489 0.489 0 .4 8 1 0.486 0.520 0 .5 3 1 0.537 0.529 0.490 0.496 0.494 0.493 0.549 0.554 0.570 0.558 0.514 0 .5 2 1 0.518 0.518 0.528 0.532 0.545 0.535 % cholesterol absorption 42.39 38.93 30.37 29.74 33.74 32.50 34.87 33.19 47.82 20.11 44.62 35.72 40.63 39.69 47.92 47.53 42.43 41.99 40.90 40.93 35.69 40.08 32.26 37.12 35.02 04-12-2006 Page A123 of A172 Appendix to TNO-report of 3M-02 Final version M ouse# 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 14C dpm feces 13292.00 12025.90 8154.44 7073.99 8303.55 8312.14 8105.89 9177.91 8404.42 9083.21 10025.30 10551.50 7998.17 9589.24 9485.67 8469.79 9318.33 9497.10 8613.92 8699.27 7646.35 10299.70 9010.87 10286.90 8794.09 9327.04 9893.72 12083.00 11744.30 10287.20 7269.37 8544.20 8283.26 7909.58 7041.53 8328.59 7120.23 8146.99 8204.53 8975.84 9015.56 7523.90 7587.01 8719.17 8811.04 7582.08 8218.83 8867.68 8808.83 8584.87 7447.43 7758.45 6896.60 7801.31 8952.17 10058.20 10221.10 8171.80 7457.41 8538.29 8381.63 7890.69 7086.95 9800.20 11238.90 11334.00 6081.05 6823.98 6967.67 7436.52 8308.62 8710.60 8595.56 8773.69 7650.67 3H dpm feces 23039.1 20891.1 14093.8 AVERAGE 11977.8 13879.6 13866.1 AVERAGE 14355.8 16142.2 14482.0 AVERAGE 16293.9 17848.5 18335.8 AVERAGE 17522.8 20188.8 20422.8 AVERAGE 18261.6 19807.5 20101.5 AVERAGE 19823.8 19531.5 17499.6 AVERAGE 20630.3 17880.3 20622.3 AVERAGE 18229.9 19419.7 20500.1 AVERAGE 22066.1 21734.5 19073.9 AVERAGE 16991.1 19484.0 19099.1 AVERAGE 18224.2 16492.5 19376.2 AVERAGE 17677.8 19926.7 19132.5 AVERAGE 20407.6 19983.1 17563.4 AVERAGE 17288.6 19191.4 19513.2 AVERAGE 18143.7 20142.1 21451.9 AVERAGE 21295.7 20799.9 18297.0 AVERAGE 17723.8 15907.7 18207.4 AVERAGE 21000.2 23550.7 23744.5 AVERAGE 18430.1 17029.8 19260.2 AVERAGE 20381.9 19487.6 17369.0 AVERAGE 23428.2 26990.4 26923.6 AVERAGE 14094.2 15200.4 16000.0 AVERAGE 18241.1 20465.5 21554.3 AVERAGE 21140.4 2 13 9 0 .2 18677.5 AVERAGE 14/3H feces 0.577 0.576 0.579 0.577 0.591 0.598 0.599 0.596 0.565 0.569 0.580 0.571 0.557 0.562 0.575 0.565 0.456 0.475 0.464 0.465 0.464 0.470 0.472 0.469 0.435 0.445 0.437 0.439 0.499 0.504 0.499 0.501 0.482 0.480 0.483 0.482 0.548 0.540 0.539 0.542 0.428 0.439 0.434 0.433 0.434 0.427 0.430 0.430 0.403 0.409 0.429 0.413 0.440 0.451 0.428 0.440 0.439 0.454 0.452 0.448 0.418 0.408 0.413 0.413 0.414 0.413 0.407 0.411 0.438 0.434 0.428 0.433 0.426 0.427 0.430 0.428 0.443 0.438 0.443 0.442 0.411 0.405 0.408 0.408 0.418 0.416 0.421 0.419 0.431 0.449 0.435 0.439 0.408 0.406 0.404 0.406 0.407 0.410 0.410 0.409 % cholesterol absorption 29.90 27.59 30.62 31.38 43.48 43.04 46.68 39.18 41.48 34.11 47.36 47.73 49.77 46.58 45.55 49.82 50.06 47.37 48.02 46.36 50.43 49.16 46.72 50.69 50.34 04-12-2006 Page A124 of A172 Appendix to TNO-report of 3M-02 G roup# 1 1 AVERAGE SD 2 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 4 4 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 7 AVERAGE SD M ouse# 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 % cholestero l absorption 4 5 .8 9 4 3 .4 8 2 5 .7 8 3 2 .9 0 3 0 .6 7 4 3 .9 5 3 0 .3 8 4 4 .1 5 3 8 .7 3 3 3 .3 8 36.9 7.2 3 3 .0 3 3 1 .8 7 4 1 .1 0 2 9 .5 6 3 5 .2 7 3 2 .7 3 2 4 .9 2 3 8 .3 9 40.11 3 2 .3 0 33.9 5.0 4 2 .3 9 3 8 .9 3 3 0 .3 7 2 9 .7 4 3 3 .7 4 3 2 .5 0 3 4 .8 7 3 3 .1 9 4 7 .8 2 20.11 34.4 7.5 4 4 .6 2 3 5 .7 2 4 0 .6 3 3 9 .6 9 4 7 .9 2 4 7 .5 3 4 2 .4 3 4 1 .9 9 4 0 .9 0 4 0 .9 3 42.2 3.7 3 5 .6 9 4 0 .0 8 3 2 .2 6 3 7 .1 2 3 5 .0 2 2 9 .9 0 2 7 .5 9 3 0 .6 2 3 1 .3 8 4 3 .4 8 34.3 4.9 4 3 .0 4 4 6 .6 8 3 9 .1 8 4 1 .4 8 34.11 4 7 .3 6 4 7 .7 3 4 9 .7 7 4 6 .5 8 4 5 .5 5 44.1 4.7 4 9 .8 2 5 0 .0 6 4 7 .3 7 4 8 .0 2 4 6 .3 6 5 0 .4 3 4 9 .1 6 4 6 .7 2 5 0 .6 9 5 0 .3 4 48.9 1.6 Final version 04-12-2006 Page A125 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 week 8/9 week 8/9 week 8/9 Intestinal cholesterol absorption, p values Mann-Whitney U-test group 1 vs 2 | group 1 vs 3 group 1 vs 4 group 1 vs 5 group 1 vs 6 group 1 vs 7 n ni p n n p n n p n n p n n p nn p 10 10 0.315 10 10 0.529 10 10 0.143 10 10 0.353 10 10 0.015 10 10 <0.001 group 2 vs 4 group 2 vs 5 group 2 vs 6 | group 2 vs 7 group 3 vs 4 group 3 vs 5 n n p n n p n_ n p n m p n n p nn p 10 10 <0.001 10 1| 0.912 10 10 <0.001 10 101 <0.001 10 10 0.009 10 10 1.000 group 3 vs 7 | group 4 vs 5 group 4 vs 6 | group 4 vs 7 group 5 vs 6 group 5 vs 7 n n p nn p n n p nn p nn p nn p 10 10 <0.001 10 101 0.002 10 10 0 . 3 1 ^ 10 101 <0.001 10 10 0.001 10 10 1<0.001 group 2 vs 3 nn p 10 10 0.796 group 3 vs 6 nn p 10 10 0.005 group 6 vs 7 nn p 10 101 0.003 p<0.05 Page A126 of A172 Appendix to TNO-report of 3M-02 Final version Appendix G. Liver weight and perigonadal fat weight and lipid contents liver G1. Liver weight and perigonadal fat weight group 1 1 1 1 1 1 1 1 1 1 AVERAGE SD 2 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 4 4 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 7 AVERAGE SD M ouse# 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 eartag LR 01 12 00 20 00 02 11 00 02 12 bodyw eight (g) 3 4 .5 3 1 .9 3 0 .4 2 8 .9 3 2 .4 30.1 2 8 .4 3 2 .8 32 28 10 21 02 01 10 01 20 00 21 10 35.2 3 0 .3 34 3 4 .9 3 0 .4 3 1 .3 3 2 .9 29.2 2 8 .8 31.2 01 02 01 11 10 01 20 12 02 10 31 31 3 3 .6 2 9 .8 27.7 3 0 .9 31.2 2 6 .3 3 2 .3 2 9 .6 10 02 00 10 01 02 00 11 00 11 2 8 .3 2 8 .5 29.1 2 9 .8 31.1 2 6 .4 2 7 .6 30.1 2 7 .8 2 8 .3 10 01 11 12 12 20 01 11 00 12 3 1 .8 2 5 .9 2 9 .6 29.2 2 9 .6 30.2 3 1 .9 30.1 29.2 2 9 .6 01 10 12 10 02 00 01 02 22 21 28 31.2 2 5 .9 2 7 .5 2 6 .9 2 5 .4 2 6 .6 2 7 .8 30 2 6 .4 20 10 02 00 12 00 00 20 10 01 2 9 .9 30 28.7 3 0 .3 2 9 .4 28. 3 28.1 28 25 28 perig onadal fat w e ight (g) 1.06 0.72 0.68 0 .3 9 0.81 0.57 0 .6 3 0 .9 4 0 .8 9 0 .4 8 0.72 0.21 1.16 0 .5 3 0.92 0 .7 8 0 .5 5 0 .4 3 0 .5 0 0 .7 4 0.87 0.92 0 .7 4 0 .2 3 0.77 0 .7 4 0 .5 9 0.37 0.42 0 .6 4 0 .7 5 0 .4 4 1.05 0 .3 3 0.61 0 .2 3 0 .2 4 0 .2 6 0 .4 3 0.42 0 .4 5 0 .3 9 0 .2 3 0 .3 0 0 .3 4 0.32 0 .3 4 0 .0 8 0.82 0 .5 4 0 .6 5 0 .3 9 0.51 0.57 0 .4 4 0.52 0.86 0.47 0 .5 8 0 .1 6 0 .2 3 0 .3 4 0 .1 4 0 .1 9 0 .2 5 0 .3 0 0.41 0.37 0.31 0.21 0 .2 8 0 .0 9 0 .3 4 0 .3 6 0 .3 3 0 .3 8 0 .3 0 0 .3 0 0 .3 5 0.32 0 .2 9 0 .3 0 0 .3 3 0 .0 3 liver w e ight liver w e ight (g) 2 .1 9 2 1.66 as % o f bw (% ) 6 .3 5 6.27 5 .4 6 1.41 1.68 4 .8 8 5 .1 9 1.7 5 .6 5 1.61 5.67 1.77 1.68 5 .4 0 5 .2 5 1.49 5.32 1.72 0.23 5 .5 4 0 .4 6 2.77 7.87 1.17 1.88 3 .8 6 5 .5 3 2 .5 3 1.68 7 .2 5 5 .5 3 1.23 3 .9 3 1.35 4 .1 0 1.84 1.53 6 .3 0 5.31 1.98 6 .3 5 1.80 5 .6 0 0.53 1.38 2 6.45 2 .2 3 7 .1 9 2.27 1.68 6 .7 6 5 .6 4 1.56 5 .6 3 2 .0 6 6.67 1.85 1.51 5 .9 3 5 .7 4 2.42 7 .4 9 2.14 7 .2 3 1.97 6.47 0.31 0.71 3 .4 6 12.23 3 .6 8 3 .6 9 3 .9 3 12.91 12.68 13.19 4 .2 3 13.60 1.94 7 .3 5 3.62 13.12 3.9 12.96 4 .0 3 3.39 14.50 11.98 3 .5 9 12.45 0.63 1.92 1.9 5.97 1.71 2 .4 8 6 .6 0 8 .3 8 1.69 5 .7 9 2 .2 5 7 .6 0 2 .4 6 8 .1 5 1.47 1.88 1.82 4.61 6 .2 5 6 .2 3 2.14 7 .2 3 1.98 0.34 6.68 1.16 3.9 13.93 4.87 4.1 15.61 15.83 4.17 15.16 4 .1 3 15.35 3 .4 8 13.70 3 .1 3 11.77 4.11 4 .7 4 14.78 15.80 4.33 16.40 4 .1 0 0.52 14.83 1.37 4 .2 9 4 .3 3 14.35 14.43 3 .8 8 13.52 4 .2 8 14.13 4 .1 5 14.12 3 .8 5 13.60 3.91 3 .8 3 13.91 13.68 3 .3 3 13.32 3.92 14.00 3 .9 8 13.91 0.30 0.37 04-12-2006 Appendix to TNO-report of 3M-02 Final version 04-12-2006 tissue perigonadal fat liver liver as % of bodyweight tissue perigonadal fat liver liver as % of bodyweight tissue perigonadal fat liver liver as % of bodyweight Liverweight; perigonadal fat weight; liverweight as % of bodyweight, p values Mann-Whitney U-test group 1 vs 2 group 1 vs 3 group 1 vs 4 group 1 vs 5 group 1 vs 6 group 1 vs 7 group 2 vs 3 nn p nn p nn E nn p nn p nn p nn p 10 10 0.912 10 10 0.315 10 10 <0.001 10 10 0.123 10 10 <0.001 10 10 <0.001 10 10 0.190 10 10 0.971 10 10 0.075 10 10 <0.001 10 10 0.043 10 10 <0.001 10 10 <0.001 10 10 0.247 10 10 0.796 10 10 0.003 10 10 <0.001 10 10 0.015 10 10 <0.001 10 10 <0.001 10 10 0.089 group 2 vs 4 group 2 vs 5 group 2 vs 6 group 2 vs 7 group 3 vs 4 group 3 vs 5 group 3 vs 6 nn p nn p nn p nn p nn p nn p nn p 10 10 <0.001 10 10 0.123 10 10 <0.001 10 10 <0.001 10 10 0.003 10 10 0.971 10 10 <0.001 10 10 <0.001 10 10 0.315 10 10 <0.001 10 10 <0.001 10 10 <0.001 10 10 0.912 10 10 <0.001 10 10 <0.001 10 10 0.105 10 10 <0.001 10 10 <0.001 10 10 <0.001 10 10 0.529 10 10 <0.001 group 3 vs 7 group 4 vs 5 group 4 vs 6 | group 4 vs 7 group 5 vs 6 group 5 vs 7 group 6 vs 7 nn p nn p nn p nn p nn p nn p nn p 10 10 <0.001 10 10 <0.001 10 10 0.105 10 10 0.796 10 10 <0.001 10 10 <0.001 10 10 0.190 10 10 <0.001 10 10 <0.001 10 10 0.043 10 10 0.105 10 10 <0.001 10 10 <0.001 10 10 0.481 10 10 <0.001 10 10 <0.001 10 10 0.003 10 10 0.003 10 10 <0.001 10 10 <0.001 10 10 0.029 p<0.05 Page A128 of A172 Appendix to TNO-report of 3M-02 Final version G2. Lipid contents liver Liverhomogenates; protein concentration mouse i 13 21 31 45 51 61 2 14 22 32 46 52 62 3 17 23 33 41 53 63 4 11 24 34 42 54 64 6 12 25 35 43 55 65 5 15 26 36 44 56 66 7 16 27 37 47 57 67 8 18 28 38 48 58 68 9 19 29 39 49 59 69 10 20 40 60 30 50 70 measured prot conc (mg/ml) well 1 well 2 0.551 0.56 0.292 0.301 0.701 0.686 1.058 1.098 0.384 0.389 0.468 0.46 1.208 1.279 0.468 0.46 0.479 0.468 0.596 0.587 1.011 0.949 0.707 0.692 1.406 1.44 1.185 1.185 0.35 0.341 0.59 0.579 0.768 0.772 0.622 0.607 0.484 0.494 1.022 1.091 0.942 0.945 0.75 0.734 0.734 0.71 0.508 0.516 0.747 0.722 0.407 0.407 1.054 1.047 0.778 0.765 0.489 0.468 0.185 0.187 0.263 0.274 0.822 0.829 0.546 0.573 1.251 1.231 1.627 1.608 0.524 0.529 0.579 0.579 0.533 0.541 0.296 0.321 0.758 0.749 0.707 0.71 0.453 0.455 0.468 0.478 0.433 0.425 0.438 0.438 1.099 1.151 0.13 0.13 0.93 0.934 1.953 2.04 0.428 0.415 0.36 0.351 0.463 0.458 1.124 1.147 0.481 0.465 0.372 0.363 0.779 0.801 0.465 0.478 0.568 0.554 0.776 0.755 0.173 0.169 0.62 0.612 2.018 2.035 0.692 0.674 0.321 0.314 0.341 0.341 0.239 0.235 0.355 0.348 0.175 0.177 0.743 0.728 1.444 1.462 dilution Protein conc (mg/ml) 20 11.11 20 5.93 20 13.87 20 21.56 20 7.73 20 9.28 20 24.87 20 9.28 20 9.47 20 11.83 20 19.60 20 13.99 20 28.46 20 23.70 20 6.91 20 11.69 20 15.40 20 12.29 20 9.78 20 21.13 20 18.87 20 14.84 20 14.44 20 10.24 20 14.69 20 8.14 20 21.01 20 15.43 20 9.57 20 3.72 20 5.37 20 16.51 20 11.19 20 24.82 20 32.35 20 10.53 20 11.58 20 10.74 20 6.17 20 15.07 20 14.17 20 9.08 20 9.46 20 8.58 20 8.76 20 22.50 20 2.60 20 18.64 20 39.93 20 8.43 20 7.11 20 9.21 20 22.71 20 9.46 20 7.35 20 15.80 20 9.43 20 11.22 20 15.31 20 3.42 20 12.32 20 40.53 20 13.66 20 6.35 20 6.82 20 4.74 20 7.03 20 3.52 20 14.71 20 29.06 04-12-2006 Page A129 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 HPTLC measurements, liver lipids: mouse# 1 13 21 31 45 51 61 2 14 22 32 46 52 62 3 17 23 33 Peak# 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 Name Width [mm] Free cholesterol 4.57 Triglycerides 8.13 Internal standard Cholesterolester 3.94 4.19 Free cholesterol 4.57 Triglycerides Internal standard 6.22 4.06 Cholesterolester 5.08 Free cholesterol 4.57 Triglycerides 7.87 Internal standard 3.94 Cholesterolester 4.06 Free cholesterol Triglycerides 3.81 5.46 Internal standard Cholesterolester 4.19 4.32 Free cholesterol 4.06 Triglycerides 6.99 Internal standard 4.19 Cholesterolester 4.83 Free cholesterol 4.57 Triglycerides 7.62 Internal standard Cholesterolester 4.32 4.7 Free cholesterol 4.19 Triglycerides 7.75 Internal standard Cholesterolester 4.06 4.32 Free cholesterol 4.57 Triglycerides Internal standard 6.73 4.06 Cholesterolester 4.45 Free cholesterol 4.32 Triglycerides 7.11 Internal standard 4.06 Cholesterolester 4.32 Free cholesterol Triglycerides 4.06 7.49 Internal standard Cholesterolester 3.17 3.81 Free cholesterol 4.45 Triglycerides 5.71 Internal standard 3.81 Cholesterolester 4.19 Free cholesterol 4.45 Triglycerides 8.64 Internal standard Cholesterolester 3.17 4.57 Free cholesterol 4.83 Triglycerides 8 Internal standard Cholesterolester 4.32 4.57 Free cholesterol 4.45 Triglycerides Internal standard 6.6 3.94 Cholesterolester 4.83 Free cholesterol 4.95 Triglycerides 4.83 Internal standard 4.06 Cholesterolester 3.94 Free cholesterol Triglycerides 4.45 6.6 Internal standard Cholesterolester 3.68 4.7 Free cholesterol 4.06 Triglycerides 6.86 Internal standard Cholesterolester 3.81 5.08 Free cholesterol 4.57 Trig lycerides Internal standard 6.22 4.19 Cholesterolester 4.57 Pos [mm] 6.73 21.84 27.3 35.31 6.22 19.94 26.42 34.8 5.97 19.68 26.16 34.42 6.35 19.43 26.42 34.8 6.35 20.32 26.42 34.67 6.48 20.07 26.29 34.42 6.48 20.07 26.16 34.16 6.99 20.32 26.54 34.54 6.86 20.83 26.16 33.66 6.86 21.97 26.29 33.66 7.62 23.24 27.56 34.16 6.48 22.86 27.56 35.31 6.48 20.83 26.54 34.54 6.22 19.56 25.65 34.16 5.97 18.41 25.4 33.78 6.22 20.07 26.16 34.29 6.35 21.34 26.67 34.54 6.86 22.23 27.3 34.92 od-Bkg 62604 287988 22996 105220 52524 197880 24262 125607 43766 251729 26977 68880 34466 123478 27048 67378 52422 260322 24841 141768 50585 265253 24749 127056 48224 248371 28494 130184 44510 192428 25345 79085 54357 258846 23946 89672 57023 299353 22427 84768 39787 115041 21069 81470 51326 318787 21609 111253 41327 242241 25212 94035 46397 221527 27238 133113 35829 104710 25858 42916 44899 206251 22142 78487 51469 216844 25800 74388 46317 162768 26102 89651 |jg lipid/ 200 pg protein 5.44 50.09 2.00 9.15 4.33 32.62 2.00 10.35 3.24 37.32 2.00 5.11 2.55 18.26 2.00 4.98 4.22 41.92 2.00 11.41 4.09 42.87 2.00 10.27 3.38 34.87 2.00 9.14 3.51 30.37 2.00 6.24 4.54 43.24 2.00 7.49 5.09 53.39 2.00 7.56 3.78 21.84 2.00 7.73 4.75 59.01 2.00 10.30 3.28 38.43 2.00 7.46 3.41 32.53 2.00 9.77 2.77 16.20 2.00 3.32 4.06 37.26 2.00 7.09 3.99 33.62 2.00 5.77 3.55 24.94 2.00 6.87 Paae A130 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 mouse# 41 53 63 4 11 24 34 42 54 64 6 12 25 35 43 55 65 5 Peak# 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 Name Width [mm] Free cholesterol 5.08 Triglycerides 5.59 Internal standard 4.06 Cholesterolester 4.06 Free cholesterol 4.19 Triglycerides 6.86 Internal standard Cholesterolester 3.94 3.94 Free cholesterol 4.45 Triglycerides 7.49 Internal standard Cholesterolester 3.3 4.45 Free cholesterol 4.32 Triglycerides Internal standard 5.33 4.32 Cholesterolester 3.56 Free cholesterol 4.19 Triglycerides 8.51 Internal standard Cholesterolester 3.56 5.33 Free cholesterol Triglycerides 3.94 5.97 Internal standard Cholesterolester 4.45 4.95 Free cholesterol 4.19 Triglycerides 6.48 Internal standard 4.06 Cholesterolester 5.33 Free cholesterol 4.45 Triglycerides 6.48 Internal standard Cholesterolester 3.94 5.08 Free cholesterol 4.06 Triglycerides 6.6 Internal standard Cholesterolester 3.94 5.59 Free cholesterol 4.06 Triglycerides Internal standard 6.99 4.32 Cholesterolester 6.1 Free cholesterol 4.7 Triglycerides 5.97 Internal standard Cholesterolester 3.56 4.06 Free cholesterol Triglycerides 3.94 5.97 Internal standard 4.32 Cholesterolester 5.59 Free cholesterol 3.81 Triglycerides 5.46 Internal standard 3.94 Cholesterolester 4.45 Free cholesterol 4.32 Triglycerides 6.73 Internal standard Cholesterolester 4.06 4.95 Free cholesterol 4.7 Triglycerides 7.24 Internal standard Cholesterolester 3.94 4.95 Free cholesterol 3.68 Triglycerides Internal standard 6.6 3.56 Cholesterolester 5.59 Free cholesterol 3.81 Triglycerides 6.6 Internal standard Cholesterolester 3.81 5.84 Free cholesterol Triglycerides 3.56 5.71 Internal standard Choleste rolester 4.19 5.59 Pos [mm] 7.37 22.61 27.69 35.31 7.24 22.99 27.81 35.31 6.73 23.11 27.43 35.05 7.37 23.37 28.45 36.07 5.46 21.21 26.16 34.04 5.46 18.8 25.27 33.66 4.95 17.02 24 33.02 4.57 16 23.24 32.64 4.7 15.75 23.11 32.64 5.21 16 23.24 32.64 6.22 19.68 26.29 34.29 4.45 15.37 22.86 32.13 5.33 17.14 24.13 33.02 5.59 19.05 24.77 33.15 5.46 20.57 25.53 33.4 3.94 13.97 21.21 30.35 3.94 13.84 20.96 30.35 4.19 13.08 20.7 30.23 od-Bkg 39765 132487 27644 37392 49635 246286 23327 123642 60183 294481 22239 141459 38024 104943 29874 26558 35962 307860 24049 107934 40358 115325 25364 52857 42991 172245 24996 73646 56968 192630 26017 123337 56224 215795 27127 153105 55767 238689 31249 162067 53651 199383 25618 75588 38266 151763 32037 54371 49570 149995 26617 46177 61124 219127 28657 145012 56257 295337 28462 97524 48925 249297 28191 157664 65477 276227 27578 178277 49411 189703 29682 95600 |jg lipid/ 200 |jg protein 2.88 19.17 2.00 2.71 4.26 42.23 2.00 10.60 5.41 52.97 2.00 12.72 2.55 14.05 2.00 1.78 2.99 51.20 2.00 8.98 3.18 18.19 2.00 4.17 3.44 27.56 2.00 5.89 4.38 29.62 2.00 9.48 4.15 31.82 2.00 11.29 3.57 30.55 2.00 10.37 4.19 31.13 2.00 5.90 2.39 18.95 2.00 3.39 3.72 22.54 2.00 3.47 4.27 30.59 2.00 10.12 3.95 41.51 2.00 6.85 3.47 35.37 2.00 11.19 4.75 40.07 2.00 12.93 3.33 25.57 2.00 6.44 Page A131 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 mouse# 15 26 36 44 56 66 7 16 27 37 47 57 67 8 18 28 38 48 Peak# 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 Name Width [mm] Free cholesterol Triglycerides 3.3 5.71 Internal standard Cholesterolester 4.19 5.33 Free cholesterol 3.43 Triglycerides 7.49 Internal standard 3.81 Cholesterolester 5.59 Free cholesterol 3.94 Triglycerides 6.35 Internal standard Cholesterolester 3.81 5.46 Free cholesterol 3.56 Triglycerides Internal standard Cholesterolester 5.71 3.81 4.95 Free cholesterol 3.94 Triglycerides 6.6 Internal standard Cholesterolester 3.68 5.33 Free cholesterol 4.19 Triglycerides 7.37 Internal standard 3.68 Cholesterolester 5.46 Free cholesterol 4.45 Triglycerides 5.97 Internal standard Cholesterolester 4.19 4.7 Free cholesterol 4.7 Triglycerides 6.35 Internal standard Cholesterolester 4.19 3.68 Free cholesterol 4.83 Triglycerides Internal standard 6.99 4.7 Cholesterolester 4.57 Free cholesterol 4.32 Triglycerides 6.22 Internal standard Cholesterolester 4.06 4.45 Free cholesterol Triglycerides 3.94 6.6 Internal standard 3.81 Cholesterolester 4.06 Free cholesterol 4.19 Triglycerides 5.71 Internal standard 3.68 Cholesterolester 4.06 Free cholesterol 4.7 Triglycerides 7.49 Internal standard Cholesterolester 3.43 5.08 Free cholesterol 3.81 Triglycerides 5.59 Internal standard Cholesterolester 3.81 4.06 Free cholesterol 3.94 Triglycerides Internal standard 5.84 3.94 Cholesterolester 4.45 Free cholesterol 4.32 Triglycerides 5.71 Internal standard Cholesterolester 3.81 4.45 Free cholesterol Triglycerides 4.06 5.59 Internal standard 3.81 Cholesterolester 4.45 Free cholesterol 4.32 Triglycerides 6.6 Internal standard 3.17 Cho leste rolester 4.7 Pos [mm] 3.94 12.57 20.45 30.1 3.94 13.84 21.08 30.73 4.32 14.48 22.1 31.5 4.19 14.73 22.48 31.62 4.57 16.13 23.37 32.26 5.33 18.16 24.51 33.02 5.33 18.92 25.27 33.27 5.59 20.32 25.91 33.27 5.84 21.21 27.69 35.69 5.71 20.45 26.92 34.92 5.97 20.07 26.42 34.54 5.97 19.3 25.65 33.78 6.48 20.45 25.65 33.66 6.99 20.45 25.91 33.66 7.11 21.21 25.91 33.53 6.48 20.83 25.53 32.89 7.37 22.23 26.8 33.91 7.75 23.88 27.43 34.16 od-Bkg 51117 186121 31056 108021 51578 314298 30069 134094 49352 209014 27111 117556 43993 173724 24940 61245 53573 223574 24814 161398 55464 270083 24336 153330 51342 176085 23750 76943 47717 148024 25114 60069 45004 193690 27970 60245 43432 150439 25551 98765 42568 194874 23418 72154 40720 177809 27101 69768 52458 292884 29963 160643 50307 162127 27192 70970 56774 225869 27244 91446 49756 171023 26319 87109 41083 144165 27516 61184 55902 285090 26432 119215 |jg lipid/ 200 |jg protein 3.29 23.97 2.00 6.96 3.43 41.81 2.00 8.92 3.64 30.84 2.00 8.67 3.53 27.86 2.00 4.91 4.32 36.04 2.00 13.01 4.56 44.39 2.00 12.60 4.32 29.66 2.00 6.48 3.80 23.58 2.00 4.78 3.22 27.70 2.00 4.31 3.40 23.55 2.00 7.73 3.64 33.29 2.00 6.16 3.01 26.24 2.00 5.15 3.50 39.10 2.00 10.72 3.70 23.85 2.00 5.22 4.17 33.16 2.00 6.71 3.78 25.99 2.00 6.62 2.99 20.96 2.00 4.45 4.23 43.14 2.00 9.02 Page A132 of A172 Appendix to TNO-report of 3M-02 Final version mouse# 58 68 9 19 29 39 49 59 69 10 20 30 40 50 60 70 Peak# 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 Name Width [mm] Pos [mm] Free cholesterol 3.81 7.11 Triglycerides 6.73 23.24 Internal standard 3.43 27.43 Cholesterolester 4.57 34.16 Free cholesterol 3.56 4.57 Triglycerides 8.89 14.61 Internal standard 4.06 22.1 Cholesterolester 5.71 32.13 Free cholesterol 3.17 4.57 Triglycerides 5.59 12.19 Internal standard 3.81 20.83 Cholesterolester 4.95 31.24 Free cholesterol 3.3 4.32 Triglycerides 4.7 11.68 Internal standard 3.94 20.57 Cholesterolester 4.95 31.12 Free cholesterol 3.3 3.81 Triglycerides 6.99 12.57 Internal standard 3.68 20.57 Cholesterolester 5.33 31.12 Free cholesterol 3.56 3.81 Triglycerides 5.08 11.68 Internal standard 4.19 20.7 Cholesterolester 5.33 31.24 Free cholesterol 3.94 4.06 Triglycerides 4.83 11.81 Internal standard 4.32 21.34 Cholesterolester 4.95 32.13 Free cholesterol 3.94 3.81 Triglycerides 5.97 12.57 Internal standard 4.06 21.84 Cholesterolester 5.71 32.38 Free cholesterol 3.17 4.7 Triglycerides 8.13 14.86 Internal standard 4.32 22.99 Cholesterolester 5.46 33.4 Free cholesterol 3.43 4.57 Triglycerides 5.21 13.59 Internal standard 3.68 22.99 Cholesterolester 4.83 33.27 Free cholesterol 3.43 4.83 Triglycerides 6.22 14.99 Internal standard 3.68 23.75 Cholesterolester 4.7 33.91 Free cholesterol 3.17 5.08 Triglycerides 5.08 15.49 Internal standard 3.68 24.38 Cholesterolester 4.32 34.16 Free cholesterol 4.06 8.76 Triglycerides 5.46 27.43 Internal standard 2.92 30.1 Cholesterolester 4.83 35.18 Free cholesterol 3.56 8.89 Triglycerides 4.83 25.78 Internal standard 3.43 29.34 Cholesterolester 3.94 35.18 Free cholesterol 4.19 8 Triglycerides 6.35 24.77 Internal standard 2.79 28.57 Cholesterolester 4.83 35.05 Free cholesterol 4.7 7.49 Triglycerides 7.49 23.11 Internal standard 3.17 27.81 Cholesterolester 4.45 34.8 od-Bkg 50057 254148 23859 136982 59495 368098 29699 172395 47364 186870 29695 97139 44604 114977 29508 85494 55495 290613 29976 133502 54475 146150 30815 126727 63475 140542 33224 84388 64340 238585 30644 139703 56623 368599 30442 178078 37007 124055 26723 78711 47883 216520 26901 83366 34039 136553 27780 92480 54261 222500 24418 136191 36509 87808 28028 35295 58652 238639 21843 134627 58311 269150 31958 124736 |jg lipid/ 200 gg protein 4.20 42.61 2.00 11.48 4.01 49.58 2.00 11.61 3.19 25.17 2.00 6.54 3.02 15.59 2.00 5.79 3.70 38.78 2.00 8.91 3.54 18.97 2.00 8.23 3.82 16.92 2.00 5.08 4.20 31.14 2.00 9.12 3.72 48.43 2.00 11.70 2.77 18.57 2.00 5.89 3.56 32.20 2.00 6.20 2.45 19.66 2.00 6.66 4.44 36.45 2.00 11.15 2.61 12.53 2.00 2.52 5.37 43.70 2.00 12.33 3.65 33.69 2.00 7.81 04-12-2006 Page A133 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 G roup# AVERAGE SD 2 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 3 AVERAGE SD i AVERAGE SD 5 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 7 AVERAGE SD M ouse# 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 Liver lipids (pg/200 pg protein) Free cholesterol T riglycerides C h oleste ro le ste r 5.44 3.51 2.77 5 0 .0 9 30.37 16.20 9.15 6.24 3.32 2.55 3.33 14.05 25.57 1.78 6.44 4.19 4.32 3 1 .1 3 2 9 .6 6 5.90 6.48 3.70 2 3 .8 5 5.22 3.19 2.77 25.17 18.57 6.54 5.89 2.99 2.39 4.33 4.54 3.29 3.80 4.06 4.17 3.02 3.56 5 1 .2 0 18.95 32.62 4 3 .2 4 23.97 2 3 .5 8 3 7 .2 6 3 3 .1 6 15.59 3 2 .2 0 8.98 3.39 10.35 7.49 6.96 4.78 7.09 6.71 5.79 6.20 3.24 5.09 3.99 3.18 3.72 3.43 3.22 3.78 3.70 2.61 37.32 5 3 .3 9 33.62 18.19 2 2 .5 4 41.81 2 7 .7 0 2 5 .9 9 3 8 .7 8 12.53 5.11 7.56 5.77 4.17 3.47 8.92 4.31 6.62 8.91 2.52 2.55 3.78 3.55 3.44 4.27 3.64 3.40 2.99 3.54 2.45 18.26 2 1 .8 4 2 4 .9 4 2 7 .5 6 3 0 .5 9 3 0 .8 4 2 3 .5 5 2 0 .9 6 18.97 19.66 4.98 7.73 6.87 5.89 10.12 8.67 7.73 4.45 8.23 6.66 2.88 4.38 3.95 3.53 4.22 4.75 3.64 4.23 3.82 5.37 19.17 29.62 41.51 2 7 .8 6 41.92 59.01 3 3 .2 9 4 3 .1 4 16.92 4 3 .7 0 2.71 9.48 6.85 4.91 11.41 10.30 6.16 9.02 5.08 12.33 4.09 3.28 4.26 4.15 3.47 4.32 3.01 4.20 4.20 4.44 42.87 3 8 .4 3 4 2 .2 3 31.82 35.37 3 6 .0 4 2 6 .2 4 42.61 3 1 .1 4 3 6 .4 5 10.27 7.46 10.60 11.29 11.19 13.01 5.15 11.48 9.12 11.15 3.38 3.41 5.41 3.57 4.75 4.56 3.50 4.01 3.72 3.65 34.87 3 2 .5 3 52.97 3 0 .5 5 40.07 4 4 .3 9 3 9 .1 0 4 9 .5 8 4 8 .4 3 3 3 .6 9 9.14 9.77 12.72 10.37 12.93 12.60 10.72 11.61 11.70 7.81 Liver lipids (pg/m g protein) | Free cholestero l T riglycerides C h ole ste ro le ste r 27.22 2 5 0 .5 45.76 17.56 1 5 1 .8 31.20 13.86 81.0 16.60 12.73 70.3 8.89 16.65 1 2 7 .8 32.21 2 0 .9 4 1 5 5 .7 29.51 21.62 1 4 8 .3 32.40 18.50 1 1 9 .2 26.10 15.95 1 2 5 .9 32.71 13.85 92.8 29.45 17.89 1 3 2 .3 28.48 4.41 51.0 9.92 14.95 2 5 6 .0 44.88 11.94 94.7 16.97 2 1 .6 5 163.1 51.77 2 2 .7 0 2 1 6 .2 37.45 16.46 1 1 9 .9 34.78 19.00 1 1 7 .9 23.92 2 0 .2 8 1 8 6 .3 35.45 2 0 .8 4 1 6 5 .8 33.57 15.12 77.9 28.97 17.80 1 6 1 .0 30.99 18.07 1 5 5 .9 33.87 3.44 55.1 9.86 16.22 1 8 6 .6 25.53 2 5 .4 3 2 6 7 .0 37.80 19.95 168.1 28.83 15.91 90.9 20.84 18.62 1 1 2 .7 17.35 17.15 16.09 2 0 9 .0 1 3 8 .5 44.59 21.54 18.90 1 3 0 .0 33.10 18.51 13.03 1 9 3 .9 62.7 44.54 12.59 17.98 1 5 5 .9 28.67 3.28 61.0 11.14 12.74 91.3 24.91 18.88 17.74 1 0 9 .2 1 2 4 .7 38.67 34.35 17.20 1 3 7 .8 29.46 2 1 .3 3 1 5 2 .9 50.60 18.20 1 5 4 .2 43.36 17.00 1 1 7 .8 38.65 14.93 1 0 4 .8 22.24 17.68 94.9 41.13 12.25 98.3 33.29 16.80 1 1 8 .6 35.67 2.78 23.2 8.64 14.38 95.9 13.53 2 1 .9 0 148.1 47.41 19.77 2 0 7 .5 34.26 17.64 21.10 1 3 9 .3 2 0 9 .6 24.56 57.07 2 3 .7 5 295.1 51.49 18.18 1 6 6 .4 30.81 2 1 .1 5 2 1 5 .7 45.10 19.10 84.6 25.40 2 6 .8 5 2 1 8 .5 61.64 2 0 .3 8 178.1 39.13 3.45 63.8 15.76 2 0 .4 4 2 1 4 .4 51.34 16.39 2 1 .2 8 1 9 2 .2 211.2 37.30 53.00 2 0 .7 3 159.1 56.44 17.35 1 7 6 .9 55.93 2 1 .5 9 1 8 0 .2 65.04 15.03 1 3 1 .2 25.74 2 0 .9 8 21.00 22.22 2 1 3 .0 1 5 5 .7 1 8 2 .2 57.41 45.59 55.77 19.70 1 8 1 .6 50.36 2.49 27.5 11.40 16.92 1 7 4 .3 45.69 17.03 1 6 2 .7 48.87 2 7 .0 6 17.85 2 6 4 .8 1 5 2 .8 63.61 51.86 2 3 .7 4 2 2 .7 9 2 0 0 .3 222.0 64.65 63.01 17.51 1 9 5 .5 53.61 2 0 .0 3 2 4 7 .9 58.05 18.60 2 4 2 .2 58.50 18.25 1 6 8 .4 39.03 19.98 203.1 54.69 3.43 39.4 8.45 Page A134 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 lipid free cholesterol triglyceride cholesterolester lipid free cholesterol triqlvceride cholesterolester lipid free cholesterol triqlvceride cholesterolester group 1 vs 2 nn p 10 10 0.739 10 10 0.247 10 10 0.218 group 2 vs 4 nn p 10 10 0.353 10 10 0.089 10 10 0.684 group 3 vs 7 nn p 10 10 0.247 10 10 0.075 10 10 <0.001 group 1 vs 3 nn p 10 10 0.796 10 10 0.353 10 10 0.912 group 2 vs 5 nn p 10 10 0.218 10 10 0.436 10 10 0.529 group 4 vs 5 nn p 10 10 0.023 10 10 0.035 10 10 0.579 lipid contents liver, p values Mann-Whitney U-test group 1 vs 4 group 1 vs 5 group 1 vs 6 nn p nn p nn p 10 10 0.853 10 10 0.105 10 0.218 10 10 0.631 10 10 0.105 10 0.004 10 10 0.105 10 10 0.190 10 0.002 group 2 vs 6 group 2 vs 7 group 3 vs 4 nn E nn p nn p 10 10 0.315 10 10 0.353 10 10 0.529 10 10 0.280 10 10 0.052 10 10 0.143 10 10 0.004 10 10 <0.001 10 10 0.143 group 4 vs 6 | group 4 vs 7 group 5 vs 6 nn p nn p nn p 10 10 0.052 10 10 0.075 10 10 0.739 10 10 <0.001 10 10 <0.001 10 10 0.971 10 10 0.005 10 10 <0.001 10 10 0.105 group 1 vs 7 nn p 10 10 0.190 10 10 0.002 10 10 <0.001 group 3 vs 5 nn p 10 10 0.089 10 10 0.353 10 10 0.105 group 5 vs 7 nn p 10 10 0.579 10 10 0.315 10 10 0.015 group 2 vs 3 nn p 10 10 0.739 10 10 0.912 10 10 0.280 group 3 vs 6 nn p 10 10 0.089 10 10 0.247 10 10 0.001 group 6 vs 7 nn p 10 10 0.971 10 10 0.315 10 10 0.393 p<0.05 Page A135 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 H. HMG-CoA reductase and cholesterol-7a-hydroxylase activity in liver microsomes and sterol27-hydroxylase activity in liver mitochondria H1. HMG-CoA reductase and cholesterol-7a-hydroxylase activity in liver microsomes Protein concentration isolated microsomes M ic ro s o m e s fo r H M G C o A re d u c ta s e d e te rm in a tio n m ouse 1 13 21 31 45 51 61 2 14 22 32 46 52 62 3 17 23 33 41 53 63 4 11 24 34 42 54 64 6 12 25 35 43 55 65 5 15 26 36 44 56 66 7 16 27 37 47 57 67 8 18 28 38 48 58 68 9 19 29 39 49 59 69 10 20 40 60 30 50 70 m easured p ro t co n c (m g/m l) w ell 1 0 .8 2 8 w ell 2 0.866 0 .7 2 5 0 .7 3 9 1 .0 5 2 1.102 1.42 1 .5 2 5 0 .9 2 7 0 .9 7 7 0 .6 5 9 0 .6 5 4 0 .6 5 4 0.688 0 .7 6 3 0.801 1 .0 1 9 1 .0 7 3 0 .7 8 8 0 .8 1 8 1 .6 6 7 1 .8 0 3 1.031 1 .0 5 6 0 .6 4 0 .6 4 7 0.691 0 .7 0 9 0 .7 8 9 0 .8 2 8 0 .6 6 9 0.688 0 .7 1 8 0 .7 3 9 0 .8 7 6 0.888 0 .6 6 4 1.86 0 .6 7 7 1 .9 8 3 1 .7 3 3 1.851 0 .5 8 3 0 .6 0 4 0 .7 5 2 0 .7 7 3 0 .7 1 8 0 .7 2 9 1 .1 2 4 1.161 0 .7 3 4 0 .7 5 2 1 .5 5 5 1 .6 9 6 1 .7 5 6 1.961 0.7 0.723 0 .5 1 9 0.521 0 .8 2 2 0 .8 4 6 1 .2 2 3 1 .3 0 8 1 .1 3 6 1 .1 7 6 1 .6 4 9 1.791 0.651 0 .6 4 3 0 .6 2 2 0 .6 2 8 0 .9 8 1.041 0 .9 8 0.991 0 .7 6 3 0 .7 9 6 0.881 0.91 1 .1 4 9 1 .2 1 6 1.2 1.281 0.66 0 .7 3 4 0 .5 9 7 0 .6 4 1 .1 2 7 1 .1 9 8 1 .2 5 4 1 .3 1 5 0 .6 7 0 .6 9 9 1 .6 9 7 1 .7 1 2 1.641 1 .8 2 3 0 .6 3 7 0.668 0 .7 9 4 0 .8 2 6 0 .8 3 2 0 .8 5 9 1.63 1 .5 5 3 0 .7 9 6 0 .8 1 7 1 .7 4 7 1 .8 9 9 0 .6 3 6 0 .6 3 2 1 .0 9 7 1 .1 4 9 0 .7 3 6 0 .7 6 6 0 .9 2 0 .9 0 6 1 .5 0 3 1.47 0 .9 8 1 .0 3 4 0.621 0 .6 1 2 1 .1 5 4 1 .2 1 9 0 .7 9 8 0 .8 2 0 .8 0 7 0 .7 9 4 1.17 1 .2 0 3 1 .6 8 5 1 .6 1 2 0 .6 2 9 0 .6 5 7 1 .0 9 2 1 .0 4 8 1 .5 2 9 1 .5 9 8 d ilu tio n 20 20 20 20 20 60 60 20 20 20 20 20 60 60 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 60 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 60 20 20 20 20 20 60 20 20 20 20 20 20 20 20 P rotein conc (m g/m l) 1 6 .9 4 1 4 .6 4 2 1 .5 4 2 9 .4 5 1 9 .0 4 3 9 .3 9 4 0 .2 6 1 5 .6 4 2 0 .9 2 1 6 .0 6 3 4 .7 0 2 0 .8 7 38.61 4 2 .0 0 1 6 .1 7 1 3 .5 7 1 4 .5 7 1 7 .6 4 13.41 3 8 .4 3 3 5 .8 4 1 1 .8 7 1 5 .2 5 1 4 .4 7 2 2 .8 5 1 4 .8 6 32.51 3 7 .1 7 1 4 .2 3 1 0 .4 0 1 6 .6 8 25.31 2 3 .1 2 3 4 .4 0 3 8 .8 2 1 2 .5 0 20.21 19.71 1 5 .5 9 17.91 2 3 .6 5 24.81 1 3 .9 4 1 2 .3 7 2 3 .2 5 2 5 .6 9 1 3 .6 9 3 4 .0 9 3 4 .6 4 1 3 .0 5 1 6 .2 0 16.91 3 1 .8 3 1 6 .1 3 3 6 .4 6 3 8 .0 4 2 2 .4 6 1 5 .0 2 1 8 .2 6 2 9 .7 3 2 0 .1 4 3 6 .9 9 2 3 .7 3 1 6 .1 8 16.01 2 3 .7 3 3 2 .9 7 12.86 2 1 .4 0 3 1 .2 7 M ic ro s o m e s fo r 7 -a lp h a -h y d ro x y la s e d e te rm in a tio n m ouse 1 13 21 31 45 51 61 2 14 22 32 46 52 62 3 17 23 33 41 53 63 4 11 24 34 42 54 64 6 12 25 35 43 55 65 5 15 26 36 44 56 66 7 16 27 37 47 57 67 8 18 28 38 48 58 68 9 19 29 39 49 59 69 10 20 40 60 30 50 70 Code 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 1.10 1.11 1.12 1.13 1.14 1.15 1.16 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 2.10 2.11 2.12 2 .1 3 2 .1 4 2 .1 5 2 .1 6 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 3.9 3 .1 0 3.11 3 .1 2 3 .1 3 3 .1 4 3 .1 5 3 .1 6 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9 4 .1 0 4.11 4 .1 2 4 .1 3 4 .1 4 4 .1 5 4 .1 6 5.1 5.2 5.3 5.4 5.5 5.6 m easured p ro t co n c (m g/m l) w ell 1 w ell 2 0 .9 5 2 0 .9 9 6 0 .6 8 3 0 .7 0 3 1 .0 9 7 1 .0 4 8 1 .5 4 3 1 .4 3 8 1.222 1 .2 1 8 0 .6 5 2 0 .6 4 4 0 .6 1 2 0 .6 9 4 1 .1 0 3 1 .1 1 3 1 .3 6 6 1 .3 2 9 0 .9 9 9 0 .9 6 3 1 .5 2 4 1 .4 4 7 0.921 0 .9 0 9 0 .5 6 9 0 .5 7 5 0 .5 7 7 0.571 0 .7 0 8 0 .6 7 9 0 .5 5 3 0 .5 4 5 0 .9 1 8 0 .8 7 4 1.15 1.14 0.69 0 .6 9 4 0.5 0.436 0 .5 4 3 0 .4 7 9 0 .5 9 9 0 .5 6 9 0 .8 8 7 0 .8 3 7 0 .7 2 6 0 .7 2 4 0 .8 8 2 0 .8 9 3 0 .7 7 2 0 .8 2 9 0.541 0 .5 1 5 0.61 0 .5 7 9 0 .6 0 4 0 .6 2 4 0 .4 8 8 0 .4 9 8 0 .6 7 4 0 .6 7 1 .2 6 3 1 .3 2 9 1 .0 2 3 1 .0 5 5 0 .5 0 7 0 .4 7 2 0 .5 0 5 0 .4 9 2 0 .5 9 5 0.581 0 .8 0 8 0 .7 9 0 .9 9 4 0 .9 8 8 0 .6 7 3 0 .6 4 6 1 .1 6 4 1 .1 8 3 0 .4 7 2 0 .4 8 8 0 .3 8 5 0 .3 7 6 0 .7 9 2 0 .7 7 2 0.561 0 .5 9 2 0 .9 4 2 0 .9 3 3 1 .4 0 4 1 .5 2 7 0 .9 3 3 0 .9 4 8 0 .4 6 2 0 .4 7 9 0.35 0 .3 6 6 0.74 0 .6 9 9 0 .8 1 8 0.821 0 .8 3 7 0 .8 5 9 1 .6 0 4 1 .4 8 3 0 .8 2 9 0 .8 2 4 0.45 0 .4 6 0 .4 6 8 0 .4 5 5 0.821 0 .8 6 5 0 .8 3 2 0 .8 2 6 0 .9 1 6 0 .9 5 4 1 .1 6 4 1 .1 3 2 0 .8 9 3 0.951 0 .4 5 5 0 .4 6 8 0 .4 3 2 0.41 0.821 0 .8 4 5 0 .9 9 4 1 .0 3 9 1 .2 6 8 1 .5 1 7 0 .4 8 3 0 .5 2 5 0 .7 7 9 0 .7 8 5 0 .9 1 9 0 .8 7 0 .5 5 3 0.511 d ilu tio n 20 20 20 20 20 60 60 20 20 20 20 20 60 60 20 20 20 20 20 60 60 20 20 20 20 20 60 60 20 20 20 20 20 60 60 20 20 20 20 20 60 60 20 20 20 20 20 60 60 20 20 20 20 20 60 60 20 20 20 20 20 60 60 20 20 20 60 20 20 60 P rotein conc (m g/m l) 1 9 .4 8 1 3 .8 6 2 1 .4 5 29.81 2 4 .4 0 3 8 .8 8 3 9 .1 8 2 2 .1 6 2 6 .9 5 1 9 .6 2 29.71 1 8 .3 0 3 4 .3 2 3 4 .4 4 1 3 .8 7 1 0 .9 8 1 7 .9 2 2 2 .9 0 1 3 .8 4 2 8 .0 8 3 0 .6 6 11.68 1 7 .2 4 1 4 .5 0 1 7 .7 5 16.01 3 1 .6 8 3 5 .6 7 1 2 .2 8 9 .8 6 1 3 .4 4 2 5 .9 2 2 0 .7 8 2 9 .3 7 29.91 1 1 .7 6 1 5 .9 8 1 9 .8 2 1 3 .1 9 2 3 .4 7 2 8 .8 0 2 2 .8 3 1 5 .6 4 1 1 .5 3 1 8 .7 5 29.31 18.81 2 8 .2 3 2 1 .4 8 1 4 .3 9 1 6 .3 9 1 6 .9 6 3 0 .8 7 1 6 .5 3 2 7 .3 0 2 7 .6 9 1 6 .8 6 1 6 .5 8 1 8 .7 0 2 2 .9 6 1 8 .4 4 2 7 .6 9 2 5 .2 6 1 6 .6 6 2 0 .3 3 2 7 .8 5 3 0 .2 4 1 5 .6 4 1 7 .8 9 3 1 .9 2 Page A136 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Amount isolated liver microsomes group# m ouse# 1 1 1 1 1 1 1 1 1 1 AVERAGE SD 2 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 4 4 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 7 AVERAGE SD 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 Protein conc (m g/m l) m icrosom es m icrosom es 7 alpha hydroxylase H M G C o A reduct. 19.48 16.94 22.16 15.64 13.87 11.68 16.17 11.87 11.76 12.50 12.28 14.23 15.64 13.94 14.39 13.05 16.86 22.46 16.66 16.18 estim ated pl m icrosom es 600 600 600 600 600 600 600 600 600 600 m g m icrosom es 7 alpha hydroxylase 11.688 13.296 8.322 7.008 7.056 7.368 9.384 8.634 10.116 9.996 17.24 9.86 13.86 26.95 15.98 11.53 10.98 16.39 16.58 20.33 15.25 10.40 14.64 20.92 20.21 12.37 13.57 16.20 15.02 16.01 600 600 600 600 600 600 600 600 600 600 10.344 5.916 8.316 16.17 9.588 6.918 6.588 9.834 9.948 12.198 21.45 19.62 17.92 14.5 13.44 19.82 18.75 16.96 18.7 15.64 21.54 16.06 14.57 14.47 16.68 19.71 23.25 16.91 18.26 12.86 600 600 600 600 600 600 600 600 600 600 12.87 11.772 10.752 8.7 8.064 11.892 11.25 10.176 11.22 9.384 29.81 29.71 22.9 17.75 25.92 13.19 29.31 30.87 22.96 27.85 29.45 34.70 17.64 22.85 25.31 15.59 25.69 31.83 29.73 23.73 700 700 700 700 700 600 700 700 700 700 20.867 20.797 16.03 12.425 18.144 7.914 20.517 21.609 16.072 19.495 13.84 16.01 20.78 23.47 24.4 18.3 18.81 16.53 18.44 17.89 13.41 14.86 23.12 17.91 19.04 20.87 13.69 16.13 20.14 21.40 600 600 600 600 600 600 600 600 600 600 8.304 9.606 12.468 14.082 14.64 10.98 11.286 9.918 11.064 10.734 38.88 34.32 28.08 31.68 29.37 28.8 28.23 27.3 27.69 30.24 39.39 38.61 38.43 32.51 34.40 23.65 34.09 36.46 36.99 32.97 700 700 700 700 700 700 700 700 700 700 27.216 24.024 19.656 22.176 20.559 20.16 19.761 19.11 19.383 21.168 39.18 34.44 30.66 35.67 29.91 22.83 21.48 27.69 25.26 31.92 40.26 42.00 35.84 37.17 38.82 24.81 34.64 38.04 23.73 31.27 700 700 700 700 700 700 700 700 700 700 27.426 24.108 21.462 24.969 20.937 15.981 15.036 19.383 17.682 22.344 m g m icrosom es H M G C o A reduct. 10.164 9.384 9.702 7.122 7.5 8.538 8.364 7.83 13.476 9.708 9.15 6.24 8.784 12.552 12.126 7.422 8.142 9.72 9.012 9.606 12.924 9.636 8.742 8.682 10.008 11.826 13.95 10.146 10.956 7.716 20.615 24.29 12.348 15.995 17.717 9.354 17.983 22.281 20.811 16.611 8.046 8.916 13.872 10.746 11.424 12.522 8.214 9.678 12.084 12.84 27.573 27.027 26.901 22.757 24.08 16.555 23.863 25.522 25.893 23.079 28.182 29.4 25.088 26.019 27.174 17.367 24.248 26.628 16.611 21.889 isolated m icrosom es (m g) 21.85 22.68 18.02 14.13 14.56 15.91 17.75 16.46 23.59 19.70 18.47 3.37 19.49 12.16 17.10 28.72 21.71 14.34 14.73 19.55 18.96 21.80 18.86 4.72 25.79 21.41 19.49 17.38 18.07 23.72 25.20 20.32 22.18 17.10 21.07 3.15 41.48 45.09 28.38 28.42 35.86 17.27 38.50 43.89 36.88 36.11 35.19 8.44 16.35 18.52 26.34 24.83 26.06 23.50 19.50 19.60 23.15 23.57 22.14 3.42 54.79 51.05 46.56 44.93 44.64 36.72 43.62 44.63 45.28 44.25 45.65 4.74 55.61 53.51 46.55 50.99 48.11 33.35 39.28 46.01 34.29 44.23 45.19 7.58 used liver m g m icrosom es fo r isolation (g) pe r g liver 1.92 1.76 1.45 1.19 1.49 1.48 1.42 1.6 1.52 1.31 2.52 1.04 1.8 2.23 1.48 1.05 1.16 1.67 1.34 1.79 1.76 1.98 1.97 1.5 1.39 1.78 1.67 1.35 2.18 1.14 3.1 3.33 3.33 3.53 3.89 1.72 3.21 3.43 3.64 3.19 1.71 1.51 2.32 1.47 2.14 2.17 1.32 1.65 1.62 1.86 3.49 4.36 4.1 4.17 4.13 3.13 2.78 3.57 4.17 3.85 3.85 3.86 3.27 3.92 3.7 3.48 3.27 3.36 2.92 3.48 11.38 12.89 12.43 11.87 9.77 10.75 12.50 10.29 15.52 15.04 12.24 1.89 7.74 11.69 9.50 12.88 14.67 13.66 12.70 11.71 14.15 12.18 12.09 2.12 14.66 10.81 9.90 11.59 13.00 13.32 15.09 15.05 10.17 15.00 12.86 2.10 13.38 13.54 8.52 8.05 9.22 10.04 11.99 12.80 10.13 11.32 10.90 2.00 9.56 12.27 11.35 16.89 12.18 10.83 14.77 11.88 14.29 12.67 12.67 2.13 15.70 11.71 11.36 10.78 10.81 11.73 15.69 12.50 10.86 11.49 12.26 1.88 14.44 13.86 14.24 13.01 13.00 9.58 12.01 13.69 11.74 12.71 12.83 1.45 AVERAGE SD g roup 1-7 12.26 1.97 Page A137 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Cholesterol-7-a-hydroxylase activity measurements in microsomes used per assay 420 |jg protein 20 min incubation internal standard 20 OH: 0.5 jg per determination Mouse 1 13 21 31 45 51 61 2 14 22 32 46 52 62 3 17 23 33 energy generating mix added + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix area 20 OH 7.489 7.764 8.344 7.459 7.921 8.048 7.859 8.072 8.614 8.284 8.279 7.708 7.956 8.246 8.569 8.034 8.103 8.551 8.177 7.462 8.615 8.176 7.997 8.678 7.153 8.014 7.760 7.119 8.211 8.341 7.684 7.654 8.062 8.155 8.529 8.412 8.674 8.281 9.215 7.851 8.260 8.138 9.023 9.148 8.783 7.856 7.946 7.525 7.842 7.885 8.094 7.994 7.866 7.808 area 7aOH 1.417 1.459 0.055 2.470 2.542 0.046 2.287 2.372 0.036 0.709 0.725 0.012 2.363 2.406 0.054 0.580 0.602 0.017 0.525 0.452 n.d. 2.048 2.039 0.036 0.912 0.988 0.018 1.032 1.302 0.026 0.389 0.369 n.d. 1.034 0.991 0.027 0.344 0.332 n.d. 0.414 0.408 n.d. 2.248 2.242 n.d. 2.554 2.519 0.055 2.020 2.034 0.031 0.878 0.863 n.d. |jg 7aOH formed 0.095 0.094 0.003 0.166 0.160 0.003 0.146 0.147 0.002 0.043 0.044 0.001 0.149 0.146 0.003 0.036 0.037 0.001 0.032 0.030 0.000 0.125 0.127 0.002 0.064 0.062 0.001 0.072 0.079 0.002 0.025 0.024 0.000 0.063 0.058 0.002 0.020 0.020 0.000 0.026 0.025 0.000 0.125 0.123 0.000 0.163 0.159 0.004 0.129 0.129 0.002 0.055 0.055 0.000 7 alpha hydroxylase activity (nmol/h/mg protein) 1.681 2.959 2.662 0.785 2.661 0.658 0.576 2.296 1.137 1.373 0.456 1.093 0.368 0.472 2.282 2.898 2.346 1.014 Page A138 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Mouse 41 53 63 4 11 24 34 42 54 64 6 12 25 35 43 55 65 5 15 26 energy generating mix added + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix area 20 OH 8.173 7.392 7.547 7.601 8.694 8.113 8.815 8.171 8.490 8.332 8.091 8.957 8.472 7.915 8.828 8.352 8.133 8.018 7.148 8.432 6.831 8.519 8.106 8.352 8.875 7.996 8.907 8.561 9.027 9.222 8.466 8.414 8.950 7.978 8.371 9.549 8.359 7.939 7.754 7.600 8.216 7.859 8.187 7.860 7.683 9.259 8.480 8.305 7.459 8.254 8.066 8.428 8.346 7.805 8.127 8.333 8.348 7.974 7.537 8.761 area 7aOH 3.471 2.911 0.024 0.537 0.542 n.d. 0.556 0.583 n.d. 2.127 2.288 n.d. 1.862 1.780 0.029 1.753 1.984 n.d. 0.368 0.396 n.d. 2.052 1.990 n.d. 0.496 0.455 n.d. 0.678 0.653 n.d. 1.697 1.674 0.029 6.870 6.821 0.075 1.183 1.091 0.011 0.546 0.559 n.d. 2.021 1.895 0.020 0.619 0.595 0.024 1.066 1.116 n.d. 2.606 2.667 0.010 3.369 3.371 n.d. 2.884 2.681 0.043 gg 7aOH formed 0.212 0.197 0.002 0.035 0.031 0.000 0.032 0.036 0.000 0.128 0.141 0.000 0.110 0.112 0.002 0.105 0.122 0.000 0.026 0.023 0.000 0.120 0.123 0.000 0.028 0.028 0.000 0.040 0.036 0.000 0.100 0.099 0.002 0.431 0.407 0.004 0.071 0.069 0.001 0.036 0.034 0.000 0.123 0.121 0.001 0.033 0.035 0.000 0.071 0.068 0.000 0.155 0.160 0.001 0.207 0.202 0.000 0.181 0.178 0.002 7 alpha hydroxylase activity (nmol/h/mg protein) 3.751 0.614 0.621 2.485 2.023 2.096 0.455 2.246 0.521 0.700 1.815 7.668 1.275 0.646 2.229 0.633 1.284 2.892 3.783 3.268 Page A139 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Mouse 36 44 56 66 7 16 27 37 47 57 67 8 18 28 38 48 58 68 9 19 29 energy generating mix added + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix area 20 OH 7.543 7.412 8.080 8.523 8.450 7.586 8.189 9.455 7.871 9.543 8.293 8.583 6.707 8.792 8.695 7.664 8.129 9.510 9.979 9.559 9.372 8.482 9.335 7.948 8.375 8.607 9.266 7.959 10.692 8.987 8.115 9.262 8.761 4.538 4.178 4.434 3.873 4.184 4.643 8.343 9.026 9.171 3.989 3.669 4.843 4.001 4.331 5.012 3.910 4.155 5.027 4.100 4.005 4.765 4.192 4.391 4.288 4.084 4.075 4.527 4.149 3.944 4.428 area 7aOH 4.629 4.514 0.158 4.801 4.542 0.494 0.921 0.949 0.014 1.148 0.974 0.026 3.465 4.504 0.064 6.853 7.362 n.d. 2.836 2.618 n.d. 0.848 0.932 n.d. 4.765 4.853 0.083 0.895 1.034 0.006 0.890 0.924 0.028 2.079 2.064 0.049 1.823 1.740 0.032 4.317 4.463 0.031 0.463 0.409 n.d. 1.789 1.905 0.014 0.450 0.453 n.d. 0.821 0.866 0.037 2.296 2.352 0.023 2.755 2.820 n.d. 1.052 1.025 0.036 |jg 7aOH formed 0.307 0.305 0.010 0.282 0.269 0.033 0.056 0.050 0.001 0.060 0.059 0.000 0.258 0.256 0.004 0.447 0.453 0.000 0.142 0.137 0.000 0.050 0.050 0.000 0.284 0.282 0.004 0.056 0.048 0.000 0.055 0.050 0.000 0.229 0.247 0.006 0.235 0.208 0.003 0.259 0.247 0.002 0.058 0.056 0.000 0.224 0.220 0.001 0.058 0.055 0.000 0.100 0.108 0.004 0.274 0.268 0.003 0.337 0.346 0.000 0.127 0.130 0.004 7 alpha hydroxylase activity (nmol/h/mg protein) 5.466 4.482 0.967 1.098 4.684 8.312 2.577 0.923 5.149 0.960 0.967 4.295 4.031 4.642 1.051 4.071 1.035 1.852 4.954 6.311 2.296 Page A140 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Mouse 39 49 59 69 10 20 40 60 30 50 70 energy generating mix added + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix + NADPH mix + NADPH mix - NADPH mix area 20 OH 4.145 4.132 3.371 4.812 3.305 4.276 3.994 3.969 4.551 3.328 3.792 10.237 9.887 11.010 8.101 9.894 12.152 11.089 10.748 10.280 11.854 9.866 10.231 11.422 10.852 10.771 11.044 10.087 10.560 10.687 10.035 10.174 10.971 n.d.: not detectable area 7aOH 0.417 0.483 n.d. 1.356 0.979 n.d. 0.219 0.210 n.d. 0.710 0.735 n.d. 3.986 4.342 0.026 3.083 3.063 0.073 0.839 0.883 n.d. 0.951 0.893 0.040 2.471 2.346 n.d. 4.003 3.663 n.d. 1.536 1.606 n.d. gg 7aOH formed 0.050 0.058 0.000 0.141 0.148 0.000 0.027 0.026 0.000 0.107 0.097 0.000 0.202 0.197 0.002 0.156 0.126 0.003 0.039 0.043 0.000 0.048 0.044 0.002 0.114 0.109 0.000 0.198 0.173 0.000 0.077 0.079 0.000 7 alpha hydroxylase activity (nmol/h/mg protein) 1.004 2.669 0.498 1.880 3.654 2.542 0.757 0.816 2.057 3.435 1.436 Page A141 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 G roup i AVERAGE SD 2 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 4 4 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 7 AVERAGE SD m ouse# 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 liver w e ight (g) 2 .1 9 2 .0 0 1.66 1.41 1.68 1.70 1.61 1.77 1.68 1.49 2.77 1.17 1.88 2 .5 3 1.68 1.23 1.35 1.84 1.53 1.98 2 .0 0 2 .2 3 2.27 1.68 1.56 2 .0 6 1.85 1.51 2.42 2 .1 4 3 .4 6 3 .6 8 3 .6 9 3 .9 3 4 .2 3 1.94 3.62 3 .9 0 4 .0 3 3 .3 9 1.90 1.71 2 .4 8 1.69 2 .2 5 2 .4 6 1.47 1.88 1.82 2 .1 4 3 .9 0 4.87 4 .1 0 4.17 4 .1 3 3 .4 8 3 .1 3 4.11 4 .7 4 4 .3 3 4 .2 9 4 .3 3 3 .8 8 4 .2 8 4 .1 5 3 .8 5 3.91 3 .8 3 3 .3 3 3.92 average mg m ic ro so m e s/g liver 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 cholestero l 7 alpha hydroxylase a ctivity (nm o l/h /m g protein) per liver (nm ol/h) 1.681 4 5 .1 4 2 .2 9 6 2.282 2 .4 8 5 2.892 56.32 46.47 42.97 5 9 .5 9 1.815 4 .6 8 4 3 7 .8 3 9 2 .4 9 4 .2 9 5 4 .9 5 4 3 .6 5 4 9 3 .2 4 1 0 2 .0 7 6 6 .7 6 3 .1 0 4 1.206 6 4 .2 9 2 3 .5 5 2 .0 2 3 6 8 .7 4 7 .6 6 8 2 .9 5 9 1 1 0 .0 2 68.22 1.137 3 .7 8 3 8.312 2 .8 9 8 35.27 7 7 .9 4 1 2 5 .3 9 4 7 .9 8 4.031 6.311 2.542 9 0 .9 6 1 1 8 .4 3 6 1 .7 4 4 .1 6 6 2.442 80.47 3 0 .1 6 2.662 65.31 1.373 2 .3 4 6 3 7 .5 5 6 5 .3 0 2 .0 9 6 1.275 3 .2 6 8 2.577 4.642 2 .2 9 6 2.057 4 3 .1 9 2 4 .4 0 8 2 .5 6 5 8 .4 8 85.97 6 8 .1 5 5 4 .0 0 2 .4 5 9 0 .9 6 5 5 8 .4 9 19.37 0 .7 8 5 0 .4 5 6 33.32 2 0 .6 0 1.014 0 .4 5 5 0 .6 4 6 5 .4 6 6 4 5 .8 9 21.91 33.51 1 3 0 .0 6 0 .9 2 3 1.051 40.97 5 0 .2 6 1.004 0.757 4 9 .6 5 3 1 .4 8 1.256 1.495 45.77 3 1 .4 0 3.751 2 .2 4 6 8 7 .4 0 47.11 2 .2 2 9 4.482 67.81 92.91 2.661 1.093 5 .1 4 9 4.071 7 3 .4 3 3 2 .9 6 9 2 .8 3 9 3 .8 6 2 .6 6 9 3 .4 3 5 5 9 .5 9 9 0 .1 5 3 .1 7 9 1.221 7 3 .8 0 2 1 .6 0 0 .6 5 8 3 1 .4 8 0 .3 6 8 0 .6 1 4 0.521 0 .6 3 3 0.967 0 .9 6 0 2 2 .0 0 3 0 .8 8 2 6 .6 4 3 2 .0 5 4 1 .2 5 3 6 .8 4 1.035 0 .4 9 8 0 .8 1 6 52.17 2 8 .9 3 4 3 .3 3 0.707 0 .2 2 6 3 4 .5 6 8.94 0 .5 7 6 30.32 0.472 0.621 2 5 .0 5 2 9 .5 4 0 .7 0 0 1.284 1.098 0.967 3 6 .7 4 65.37 5 1 .8 4 4 6 .3 8 1.852 1.880 1.436 8 6 .9 8 7 6 .8 0 6 9 .0 3 1.089 0 .5 1 6 51.81 2 1 .7 9 I Page A142 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 HMG CoA reductase activity measurements internal standard mix i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i i 2 2 2 2 2 mouse# i 13 21 31 45 51 61 2 14 22 32 46 52 3 17 23 33 53 4 11 24 34 42 54 64 6 12 25 35 blanc blanc 3H dpm (internal standard) 14802 15138 14416 16500 16182 18200 16197 16086 15302 17401 19233 18151 18408 16484 14705 17314 no sample 19044 17259 17962 16815 18678 17627 16776 18636 13567 12055 12101 13870 12322 13846 15599 13354 14885 17744 17935 15926 15147 17598 18276 17701 13443 16084 13092 12500 12547 12475 15313 15836 11436 13617 15941 12877 13025 17786 15984 16769 15482 14676 12984 CM 5 CO CM 14C dpm 222 207 199 294 310 278 437 187 224 296 360 192 169 132 159 172 124 137 205 265 140 158 226 146 118 92 143 138 116 144 197 231 266 190 172 221 316 187 156 260 209 127 116 114 145 119 86 104 110 196 254 405 279 378 214 162 118 14C dpm 14C mevalonate -blanc formed (dpm) 82 169 67 135 59 125 154 284 170 320 138 231 297 558 181 342 47 93 84 147 156 247 220 369 52 86 29 54 -8 -17 19 33 HMG CoA activity pmol/min/mg protein 5.111 4.083 3.776 8.611 9.692 6.995 16.917 10.381 2.834 4.454 7.483 11.182 2.606 1.623 -0.502 1.012 32 51 -16 -28 -3 -5 65 118 125 204 00 18 33 86 140 6 13 -22 -56 -48 -121 37 -2 -5 -24 -53 48 57 130 101 207 91 156 126 214 50 96 32 64 81 140 176 293 47 81 16 36 120 227 69 160 -13 -32 -24 -58 -26 -63 5 10 -21 -40 -54 -144 -36 -80 -30 -57 56 132 114 266 265 453 139 247 238 403 74 136 1.550 -0.855 -0.154 3.566 6.174 0.000 0.990 4.257 0.408 -1.684 -3.659 0.200 -0.150 -1.599 0.237 3.938 6.260 4.731 6.481 2.896 1.949 4.246 8.885 2.450 1.098 6.883 4.862 -0.959 -1.765 -1.923 0.301 -1.223 -4.356 -2.439 -1.736 4.012 8.075 13.746 7.482 12.211 4.112 mean 4.60 6.19 8.34 13.65 3.64 9.33 2.11 0.26 1.55 0.00 4.87 0.49 2.33 0.00 0.02 0.00 5.10 5.61 2.42 6.57 1.77 5.87 0.00 0.00 0.00 0.00 6.04 10.61 8.16 Input internal standard (dpm): average mix 1 30176 29765 31362 30434 | mix 2 28810 28307 28031 28383 14C dpm HMG CoA mix: I average HMG CoA mix: 2.6 Specific activity 14C HMGCoA: 4398.46 incubation time: 30.0 liver microsomes: 0.250 mmol/l HMG CoA dpm/nmol min mg 58465 57242 55833 57180 11436 per 5 pl mix per pl mix Page A143 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 mouse# 43 55 65 5 15 26 36 44 66 7 16 27 37 blanc blanc 3Hdpm (internal standard) 16023 14382 15354 16171 15593 15352 13631 12996 13907 11471 10075 12964 13289 16215 17106 14863 14921 14914 14706 15107 13433 14340 14736 15759 16357 15923 14228 11628 Input internal standard(dpm): average [ 27932 27694 28968 28198 14Cdpm 252 192 261 211 451 136 140 139 98 109 97 93 139 173 402 338 155 168 195 321 191 287 142 154 204 179 194 144 14Cdpm 14Cmevalonate HMGCoAact. -blanc formed(dpm) pmol/min.mgeiwit 83 146 4.237 23 45 1.308 92 169 4.901 42 73 2.124 282 510 14.792 -33 -61 -1.758 -29 -60 -1.740 -30 -65 -1.888 -71 -144 -4.176 -60 -147 -4.278 -72 -202 -5.845 -76 -165 -4.795 -30 -64 -1.846 47 0.202 233 384 11.141 169 321 9.300 -14 -26 -0.767 -1 -2 -0.055 26 50 1.446 152 284 8.230 22 46 1.340 118 232 6.731 -27 -52 -1.499 -15 -27 -0.779 35 60 1.750 10 18 0.514 mean 2.77 3.51 6.52 0.00 0.00 0.00 0.00 10.22 0.00 4.84 0.00 0.00 1.13 14CHMGCoAmix: average 58407 55714 65147 59756 11951.2 per5pl mix perpl mix HMGCoAmix: 2.6mmol/l HMGCoA Specificactivity14CHMGCoA: 4596.62 dpm/nmol incubationtime: 30.0 min liver microsomes: 0.250 mg mouse# 67 8 9 19 29 39 49 59 50 70 blanc blanc 3H dpm (internal standard) 16112 16092 14295 17696 17286 16982 14651 19083 16755 16504 17225 17750 18651 15076 15831 16644 16807 14453 16679 15823 16121 16049 Input internal standard (dpm): average [ 27956 27723 28126 27935 14C dpm 284 180 129 164 379 317 145 113 142 115 247 218 209 152 159 154 195 321 191 287 95 72 14C dpm -blanc 201 97 46 81 296 234 62 30 59 32 164 135 126 69 76 71 112 238 108 204 14C mevalonate formed (dpm) 348 168 89 127 478 384 117 43 98 53 265 212 188 127 133 118 185 459 180 359 HMG CoA act. pmol/min.mg eiwit 9.646 4.648 2.467 3.526 13.251 10.658 3.254 1.198 2.706 1.479 7.358 5.874 5.216 3.522 3.697 3.283 5.142 12.738 4.996 9.969 mean 7.15 3.00 11.95 2.23 2.09 6.62 4.37 3.49 8.94 7.48 14C HMG CoA mix: average 63731 60065 63603 62466 12493.27 per 5 pl mix per pl mix HMG CoA mix: Specific activity 14C HMGCoA: incubation time: liver microsomes: 2.6 4805.1 30.0 0.250 mmol/l HMG CoA dpm/nmol min mg Page A144 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 mouse# 18 28 38 48 58 68 69 10 20 40 30 62 41 63 56 47 blanc 3H dpm (internal standard) 18621 18163 16885 17274 15495 18485 15821 17041 19175 17310 16607 14530 16586 14581 15189 15445 16021 16747 15999 14205 20405 19844 16228 14978 15343 13316 15166 16339 17431 14614 15456 15823 16766 Input internal standard (dpm): average 32959 31221 31297 31826 14C dpm 513 361 265 260 682 691 341 312 412 318 241 348 352 360 275 241 224 235 404 355 591 403 328 218 233 317 214 302 407 514 650 287 164 14C dpm 14C mevalonate -blanc formed (dpm) 349 596 197 345 101 190 96 177 518 1064 527 907 177 356 148 276 248 412 154 283 77 148 184 403 188 361 196 428 111 233 77 159 60 119 71 135 240 477 191 428 427 666 239 383 164 322 54 115 69 143 153 366 50 105 138 269 243 444 350 762 486 1001 123 247 HMG CoA act. pmol/min.mg eiwit 17.513 10.135 5.589 5.193 31.238 26.640 10.454 8.115 12.085 8.313 4.333 11.833 10.592 12.561 6.829 4.658 3.499 3.962 14.017 12.564 19.554 11.254 9.443 3.369 4.202 10.736 3.081 7.892 13.026 22.379 29.382 7.264 mean 13.82 5.39 28.94 9.28 10.20 8.08 11.58 5.74 3.73 13.29 15.40 6.41 7.47 5.49 17.70 18.32 14C HMG CoA mix: average 61119 60406 55583 59036 11807.2 per 5 |jl mix per pl mix HMG CoA mix: Specific activity 14C HMGCoA: incubation time: liver microsomes: 2.6 4541.23 30.0 0.250 mmol/l HMG CoA dpm/nmol min mg Page A145 of A172 Appendix to TNO-report of 3M-02 Final version G roup m ouse# 1 1 1 1 1 1 1 1 1 1 AVERAGE SD 2 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 4 4 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 7 AVERAGE SD 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 liver w e ig h t (g) 2.19 2.00 1.66 1.41 1.68 1.70 1.61 1.77 1.68 1.49 average mg m icro so m e s/g liver 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 2.77 1.17 1.88 2.53 1.68 1.23 1.35 1.84 1.53 1.98 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 2.00 2.23 2.27 1.68 1.56 2.06 1.85 1.51 2.42 2.14 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 3.46 3.68 3.69 3.93 4.23 1.94 3.62 3.90 4.03 3.39 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 1.90 1.71 2.48 1.69 2.25 2.46 1.47 1.88 1.82 2.14 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 3.90 4.87 4.10 4.17 4.13 3.48 3.13 4.11 4.74 4.33 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 4.29 4.33 3.88 4.28 4.15 3.85 3.91 3.83 3.33 3.92 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 12.26 H M G C oA reductase activity I (p m o l/m in /m g protein) per liver (pm o l/m in) 4.60 0.26 0.00 1 2 3 .4 3 6 .2 6 0 .0 0 2.42 0.00 4 1 .8 8 0 .0 0 0.00 4.84 3.00 11.95 5.74 0 .0 0 9 5 .4 9 6 5 .0 3 2 4 6 .2 3 1 0 4 .9 2 3.28 3.77 68.32 78.41 6.57 2 2 2 .9 6 6.04 6.19 1.55 8 6 .6 9 1 4 2 .7 5 4 8 .0 8 0.00 0.00 0.02 13.82 0 .0 0 0 .0 0 0.41 3 1 1 .8 5 2.23 3.73 4 1 .7 6 9 0 .5 6 4.02 4.33 94.51 1 0 4 .2 4 8.34 0.00 0.00 1.77 2 0 4 .5 9 0 .0 0 0 .0 0 3 6 .5 4 10.61 0.00 2 0 3 .0 0 0 .0 0 0.00 5.39 2.09 15.40 0 .0 0 99.81 6 2 .1 0 4 0 4 .1 5 4.36 5.44 1 0 1 .0 2 1 3 3 .1 3 13.65 4.87 5.10 5.87 5 7 8 .9 8 2 1 9 .7 3 2 3 0 .6 7 2 8 2 .9 6 8.16 0.00 4 2 3 .2 7 0 .0 0 1.13 2 8 .9 4 6.62 13.29 5 0 .2 4 1 3 8 3 .6 8 3 2 6 .8 7 5 5 2 .3 8 8.76 8.36 4 0 4 .8 8 3 9 2 .3 9 7.47 0.00 2.77 1 7 3 .9 9 0 .0 0 8 4 .3 0 10.22 3.64 2 1 1 .7 7 100.51 0.49 18.32 9.28 4.37 8.94 14.93 3 3 0 .2 2 2 1 4 .0 0 9 7 .4 8 2 3 4 .5 6 6.55 5.51 1 4 6 .1 8 1 0 4 .4 8 9.33 4 4 6 .2 3 2.33 5.61 0.00 3.51 1 3 9 .2 8 2 8 1 .8 1 0 .0 0 1 7 7 .8 6 17.70 6.15 7 5 5 .2 8 2 3 6 .0 5 10.20 3.49 6.69 5 1 3 .9 3 2 0 2 .8 2 3 5 5 .0 5 6.50 5.01 3 1 0 .8 3 2 1 6 .2 6 2.11 1 1 1 .2 2 6.41 5.49 0.00 6.52 0.00 7.15 3 4 0 .0 7 2 6 0 .9 8 0 .0 0 3 3 1 .5 8 0 .0 0 3 4 2 .6 1 8.08 11.58 7.48 3 7 9 .5 3 4 7 2 .6 0 359.61 5.48 3.71 2 5 9 .8 2 1 6 5 .0 3 04-12-2006 Page A146 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 m ic ro m e s ; m g p e r g liver, 7 -a lp h a -h y d ro x y la s e a c tiv ity a n d H M G C o A re d u c ta s e activity, 3 v a lu e s M a n n -W h itn e y U -te s t m icro m e s m g /g liver group 1 vs 2 nn 10 10 0.971 group 1 vs 3 nn p 10 10 0 .5 2 9 group 1 vs 4 nn 2 10 10 0 .1 4 3 group 1 vs 5 nn 2 10 10 0 .7 3 9 group 1 vs 6 nn 10 10 2 0.971 group 1 vs 7 nn 2 10 10 0 .3 1 5 grou2 2 vs 3 nn 2 10 10 0 .4 3 6 7 -a lp h a act. 10 10 0 .3 5 3 10 10 0 .3 9 3 10 10 0.002 10 10 0 .9 1 2 10 10 < 0.001 10 10 < 0.001 10 10 0 .1 0 5 7 -a lp h a act. pe r liver 10 10 0 .1 9 0 10 10 0 .6 8 4 10 10 0 .0 3 5 10 10 0 .3 5 3 10 10 < 0.001 10 10 0 .2 4 7 10 10 0 .0 8 9 H M G C o A act. 10 10 0.631 10 10 1.000 10 10 0 .0 2 9 10 10 0 .1 6 5 10 10 0 .1 0 5 10 10 0 .1 6 5 10 10 0 .7 9 6 H M G C o A a ct. p e r liv e r 10 10 0 .7 3 9 10 10 1.000 10 10 0 .0 0 7 10 10 0 .1 0 5 10 10 0 .0 0 3 10 10 0 .0 1 9 10 10 0 .7 3 9 m icro m e s m g /g liver group 2 vs 4 nn p 10 10 0 .2 1 8 group 2 vs 5 nn p 10 10 0 .5 7 9 group 2 vs 6 nn 2 10 10 0 .5 7 9 group 2 vs 7 nn 2 10 10 0 .3 1 5 group 3 vs 4 nn 10 10 2 0 .0 3 5 group 3 vs 5 nn 2 10 10 0 .9 1 2 grou2 3 vs 6 nn 2 10 10 0 .7 3 8 7 -a lp h a act. 10 10 < 0.001 10 10 0 .5 2 9 10 10 < 0.001 10 10 < 0.001 10 10 0.002 10 10 0 .1 9 0 10 10 < 0.001 7 -a lp h a act. pe r liver 10 10 0 .0 0 9 10 10 0 .6 8 4 10 10 < 0.001 10 10 0 .0 4 3 10 10 0 .0 5 2 10 10 0 .0 7 5 10 10 0 .0 0 5 H M G C o A act. 10 10 0 .1 9 0 10 10 0 .2 4 7 10 10 0 .2 4 7 10 10 0 .3 1 5 10 10 0 .2 1 8 10 10 0 .2 8 0 10 10 0 .2 1 8 H M G C o A a ct. p e r liv e r 10 10 0 .0 1 5 10 10 0 .2 4 7 10 10 0 .0 1 5 10 10 0 .0 3 5 10 10 0.011 10 10 0 .1 9 0 10 10 0 .0 2 3 m icro m e s m g /g liver group 3 vs 7 nn 2 10 10 0 .7 9 6 group 4 vs 5 nn p 10 10 0 .0 6 3 group 4 vs 6 nn 2 10 10 0 .0 2 9 group 4 vs 7 nn 2 10 10 0 .0 2 9 group 5 vs 6 nn 10 10 2 0.481 group 5 vs 7 nn 2 10 10 0.971 grou2 6 vs 7 | nn 2 10 10 0 .1 4 3 7 -a lp h a act. 10 10 0.001 10 10 0.002 10 10 0 .5 2 9 10 10 0 .5 2 9 10 10 < 0.001 10 10 < 0.001 10 10 0 .1 4 3 7 -a lp h a act. pe r liver 10 10 0.631 10 10 0 .0 1 5 10 10 0 .3 5 3 10 10 0 .3 5 3 10 10 < 0.001 10 10 0 .0 2 9 10 10 0 .1 2 3 H M G C o A act. 10 10 0 .4 3 6 10 10 0.631 10 10 0 .6 8 4 10 10 0 .5 7 9 10 10 0 .9 1 2 10 10 0 .6 8 4 10 10 0 .9 1 2 H M G C o A a ct. p e r liv e r 10 10 0 .0 6 3 10 10 0 .0 4 3 10 10 0.631 10 10 0 .6 8 4 10 10 0 .0 5 2 10 10 0 .0 6 3 10 10 0 .8 5 3 | 2<005 Page A147 of A172 Appendix to TNO-report of 3M-02 Final version H2. Cholesterol-27-hydroxylase activity in mitochondria Protein concentration isolated mitochondria M itochondria mouse i 13 21 31 45 51 61 2 14 22 32 46 52 62 3 17 23 33 41 53 63 4 11 24 34 42 54 64 6 12 25 35 43 55 65 5 15 26 36 44 56 66 7 16 27 37 47 57 67 8 18 28 38 48 58 68 9 19 29 39 49 59 69 10 20 40 60 30 50 70 measured prot conc (mg/ml) well 1 well 2 0.772 0.8 0.699 0.699 0.848 0.908 1.508 1.499 0.925 0.973 0.784 0.813 0.865 0.881 1.143 1.162 0.918 0.931 0.945 1.022 1.192 1.104 1.043 1.062 1.26 1.236 1.201 1.204 0.81 0.81 0.57 0.54 0.915 0.949 1.036 1.092 0.699 0.655 1.033 0.942 0.898 0.839 0.576 0.587 0.726 0.672 0.969 0.959 1.532 1.43 0.784 0.852 0.98 0.997 1.201 1.28 0.699 0.658 0.383 0.359 0.931 0.861 1.37 1.235 0.842 0.845 0.945 0.976 0.949 0.901 0.649 0.637 0.648 0.635 0.775 0.799 0.678 0.705 0.757 0.757 0.84 0.843 1.031 0.998 0.754 0.714 0.467 0.443 0.876 0.886 1.171 1.1 0.554 0.554 0.847 0.809 0.578 0.596 0.616 0.596 0.697 0.7 0.728 0.745 1.808 1.903 1.086 0.85 1.261 1.147 0.734 0.766 0.616 0.611 0.691 0.659 0.847 0.847 1.255 1.251 0.76 0.751 0.85 0.796 0.751 0.728 0.837 0.821 0.84 0.809 1.344 1.34 0.769 0.827 0.642 0.598 0.987 0.965 1.039 0.926 dilution 50 50 50 50 50 100 100 50 50 50 100 50 100 100 50 50 50 100 50 100 100 50 50 50 100 50 100 100 50 50 50 100 50 100 100 50 50 50 50 50 100 100 50 50 50 100 50 100 100 50 50 50 100 50 100 100 50 50 50 100 50 100 100 50 50 100 100 50 50 100 Protein conc (mg/ml) 39.30 34.95 43.90 75.18 47.45 79.85 87.30 57.63 46.23 49.18 114.80 52.63 124.80 120.25 40.50 27.75 46.60 106.40 33.85 98.75 86.85 29.08 34.95 48.20 148.10 40.90 98.85 124.05 33.93 18.55 44.80 130.25 42.18 96.05 92.50 32.15 32.08 39.35 34.58 37.85 84.15 101.45 36.70 22.75 44.05 113.55 27.70 82.80 58.70 30.30 34.93 36.83 185.55 48.40 120.40 75.00 30.68 33.75 42.35 125.30 37.78 82.30 73.95 41.45 41.23 134.20 79.80 31.00 48.80 98.25 04-12-2006 Page A148 of A172 Appendix to TNO-report of 3M-02 Final version Amount isolated mitochondria group# 1 i 1 1 1 1 1 AVERAGE SD 2 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 4 4 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 7 AVERAGE SD mouse# 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 Protein conc estim a te d pl m itochondria (m g/m l) m icrosom es 39.30 600 57.63 600 40.50 600 29.08 600 32.15 600 33.93 600 36.70 600 30.30 600 30.68 600 41.45 600 34.95 18.55 34.95 46.23 32.08 22.75 27.75 34.93 33.75 41.23 600 600 600 600 600 600 600 600 600 600 43.90 49.18 46.60 48.20 44.80 39.35 44.05 36.83 42.35 31.00 600 600 600 600 600 600 600 600 600 600 75.18 114.80 106.40 148.10 130.25 34.58 113.55 185.55 125.30 134.20 700 700 700 700 700 600 700 700 700 700 33.85 40.90 42.18 37.85 47.45 52.63 27.70 48.40 37.78 48.80 600 600 600 600 600 600 600 600 600 600 79.85 124.80 98.75 98.85 96.05 84.15 82.80 120.40 82.30 79.80 700 700 700 700 700 700 700 700 700 700 87.30 120.25 86.85 124.05 92.50 101.45 58.70 75.00 73.95 98.25 700 700 700 700 700 700 700 700 700 700 isolated m itochondria (m g) 23.58 34.58 24.30 17.45 19.29 20.36 22.02 18.18 18.41 24.87 20.97 11.13 20.97 27.74 19.25 13.65 16.65 20.96 20.25 24.74 26.34 29.51 27.96 28.92 26.88 23.61 26.43 22.10 25.41 18.60 52.62 80.36 74.48 103.67 91.18 20.75 79.49 129.89 87.71 93.94 20.31 24.54 25.31 22.71 28.47 31.58 16.62 29.04 22.67 29.28 55.90 87.36 69.13 69.20 67.24 58.91 57.96 84.28 57.61 55.86 61.11 84.18 60.80 86.84 64.75 71.02 41.09 52.50 51.77 68.78 64.28 14.24 used liver mg m itochondria fo r isolation (g) per g liver 1 .9 2 12.28 1.76 19.64 1.45 16.76 1.19 14.66 1.49 12.95 1.48 13.75 1.42 1.6 1.52 15.51 11.36 12.11 1.31 18.98 14.80 2.89 2.52 8.32 1.04 1.8 10.70 11.65 2.23 12.44 1.48 13.00 1.05 13.00 1.16 14.35 1.67 12.55 1.34 15.11 1 .7 9 13.82 12.49 1 .9 4 1 .7 6 14.97 1.98 14.90 1.97 14.19 1.5 19.28 1.39 19.34 1.78 13.26 1.67 15.83 1.35 2.18 16.37 11.66 1 .1 4 16.32 15.61 2.42 3.1 16.98 3.33 24.13 3.33 22.37 3.53 29.37 3.89 23.44 1.72 12.06 3 .2 1 24.76 3.43 37.87 3.64 24.10 3.19 29.45 24.45 7.03 1.71 11.88 1.51 16.25 2.32 10.91 1.47 15.45 2.14 13.30 2.17 14.55 1.32 12.59 1.65 17.60 1.62 1.86 13.99 15.74 14.23 2.09 3.49 16.02 4.36 20.04 4.1 16.86 4.17 16.59 4.13 16.28 3.13 18.82 2.78 20.85 3.57 23.61 4.17 13.82 3.85 14.51 17.74 3.05 3.85 15.87 3.86 21.81 3.27 18.59 3.92 22.15 3.7 17.50 3.48 20.41 3.27 12.57 3.36 15.63 2.92 17.73 3.48 19.76 18.20 2.99 AVERAGE SD group 1-3,5 14.28 2.55 AVERAGE SD group 4 24.45 7.03 AVERAGE SD group 6,7 17.97 2.95 04-12-2006 Page A149 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Cholesterol-27-hydroxylase activity measurements used per assay 420 |jg protein 20 min incubation internal standard 20 OH: 0.5 jg per determination Mouse energy generating area 20 OH area 27OH mix added 1 + NADPH mix 10.798 13.936 + NADPH mix 10.39 13.174 - NADPH mix 7.98 0.136 13 + NADPH mix 11.806 20.962 + NADPH mix 12.439 19.566 - NADPH mix 8.742 0.125 21 + NADPH mix 11.5 19.885 + NADPH mix 11.782 16.14 - NADPH mix 8.867 0.126 31 + NADPH mix 9.271 8.456 + NADPH mix 10.042 9.881 - NADPH mix 8.477 0.038 45 + NADPH mix 12.431 18.514 + NADPH mix 12.184 17.151 - NADPH mix 8.816 0.07 51 + NADPH mix 10.388 10.217 + NADPH mix - NADPH mix 10.595 8.259 11.997 0.113 61 + NADPH mix 9.893 11.615 + NADPH mix 10.305 11.839 - NADPH mix 8.75 0.068 2 + NADPH mix 9.624 11.398 + NADPH mix - NADPH mix 10.36 8.95 13.32 n.a. 14 + NADPH mix 11.022 14.253 + NADPH mix 11.6 14.61 - NADPH mix 9.308 0.023 22 + NADPH mix 10.919 15.555 + NADPH mix 10.512 16.346 - NADPH mix 9.52 0.074 32 + NADPH mix 8.987 8.043 + NADPH mix - NADPH mix 9.298 8.538 8.372 0.023 46 + NADPH mix 10.614 15.727 + NADPH mix 10.223 15.178 - NADPH mix 9.715 0.048 52 + NADPH mix 9.353 9.827 + NADPH mix - NADPH mix 10.539 8.851 9.649 0.071 62 + NADPH mix 10.024 6.711 + NADPH mix 9.352 6.677 - NADPH mix 8.92 n.a. 3 + NADPH mix 12.459 19.765 + NADPH mix 11.384 15.393 - NADPH mix 9.006 n.a. 17 + NADPH mix 10.383 12.005 + NADPH mix 14.276 18.144 - NADPH mix 9.026 n.a. 23 + NADPH mix 9.646 14.544 + NADPH mix 10.293 14.524 - NADPH mix 7.233 n.a. 33 + NADPH mix 8.216 7.206 + NADPH mix 8.156 6.744 - NADPH mix 7.185 0.249 |jg 27 OH formed 0.645 0.634 0.009 0.888 0.786 0.007 0.865 0.685 0.007 0.456 0.492 0.002 0.745 0.704 0.004 0.492 0.566 0.007 0.587 0.574 0.004 0.592 0.643 0.000 0.647 0.630 0.001 0.712 0.777 0.004 0.447 0.450 0.001 0.741 0.742 0.002 0.525 0.458 0.004 0.335 0.357 0.000 0.793 0.676 0.000 0.578 0.635 0.000 0.754 0.706 0.000 0.439 0.413 0.017 27- hydroxylase activity (nmol/h/mg protein) 11.659 15.332 14.181 8.715 13.306 9.645 10.656 11.407 11.766 13.689 8.267 13.654 9.007 6.389 13.571 11.209 13.480 7.549 Page A150 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Mouse energy generating area 20 OH area 27OH mix added 41 + NADPH mix + NADPH mix 10.176 9.541 4.943 4.889 - NADPH mix 7.88 n.a. 53 + NADPH mix 7.856 4.981 + NADPH mix 7.979 4.873 - NADPH mix 7.279 n.a. 63 + NADPH mix 10.998 7.897 + NADPH mix - NADPH mix 8.797 7.705 6.181 0.086 4 + NADPH mix 9.576 11.39 + NADPH mix - NADPH mix 10.192 7.719 12.068 n.a. 11 + NADPH mix + NADPH mix 11.137 9.797 8.145 7.601 - NADPH mix 8.556 0.038 24 + NADPH mix 10.407 11.002 + NADPH mix - NADPH mix 9.642 6.778 11.512 n.a. 34 + NADPH mix 6.577 3.674 + NADPH mix 9.528 5.095 - NADPH mix 7.252 n.a. 42 + NADPH mix 9.538 11.731 + NADPH mix 9.074 10.387 - NADPH mix 7.471 0.027 54 + NADPH mix 8.887 6.229 + NADPH mix 8.267 5.477 - NADPH mix 7.436 n.a. 64 + NADPH mix 8.585 6.457 + NADPH mix 8.945 6.783 - NADPH mix 6.454 n.a. 6 + NADPH mix 11.823 13.325 + NADPH mix - NADPH mix 8.846 8.775 9.816 0.057 12 + NADPH mix 9.224 1.784 + NADPH mix 9.098 1.721 - NADPH mix 9.234 n.a. 25 + NADPH mix 10.72 7.132 + NADPH mix 9.542 7.327 - NADPH mix 8.864 0.031 35 + NADPH mix 9.856 5.695 + NADPH mix - NADPH mix 10.84 8.053 4.8 n.a. 43 + NADPH mix 10.178 12.222 + NADPH mix 10.114 10.741 - NADPH mix 7.765 n.a. 55 + NADPH mix 8.696 5.552 + NADPH mix 8.713 5.349 - NADPH mix 8.251 0.032 65 + NADPH mix 9.579 6.842 + NADPH mix - NADPH mix 9.473 8.811 7.217 0.056 5 + NADPH mix 9.569 7.618 + NADPH mix 9.56 7.922 - NADPH mix 8.442 0.004 15 + NADPH mix 10.061 8.488 + NADPH mix 10.559 7.934 - NADPH mix 9.105 n.a. 26 + NADPH mix 9.863 7.929 + NADPH mix 9.469 8.269 - NADPH mix 8.926 n.a. gg 27 OH formed 0.243 0.256 0.000 0.317 0.305 0.000 0.359 0.351 0.006 0.595 0.592 0.000 0.366 0.388 0.002 0.529 0.597 0.000 0.279 0.267 0.000 0.615 0.572 0.002 0.350 0.331 0.000 0.376 0.379 0.000 0.564 0.555 0.003 0.097 0.095 0.000 0.333 0.384 0.000 0.289 0.221 0.000 0.600 0.531 0.000 0.319 0.307 0.002 0.357 0.381 0.003 0.398 0.414 0.000 0.422 0.376 0.000 0.402 0.437 0.000 27- hydroxylase activity (nmol/h/mg protein) 4.610 5.749 6.458 10.962 6.920 10.396 5.049 10.933 6.297 6.976 10.270 1.767 6.619 4.714 10.450 5.748 6.758 7.499 7.366 7.746 Page A151 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Mouse energy generating area 20 OH area 27OH mix added 36 + NADPH mix 9.147 4.853 + NADPH mix 9.469 4.856 - NADPH mix 7.56 0.022 44 + NADPH mix 9.972 8.19 + NADPH mix 11.897 8.239 - NADPH mix 8.394 n.a. 56 + NADPH mix 9.607 5.319 + NADPH mix 9.685 4.876 - NADPH mix 8.852 0.035 66 + NADPH mix 9.829 7.898 + NADPH mix 10.203 7.893 - NADPH mix 9.701 0.042 7 + NADPH mix 10.39 6.813 + NADPH mix 9.963 7.322 - NADPH mix 9.004 n.a. 16 + NADPH mix 9.887 6.158 + NADPH mix 9.808 5.884 - NADPH mix 8.749 n.a. 27 + NADPH mix 10.948 8.509 + NADPH mix 11.307 8.456 - NADPH mix 9.47 0.018 37 + NADPH mix 10.004 6.283 + NADPH mix 9.859 6.029 - NADPH mix 8.538 n.a. 47 + NADPH mix 9.054 6.579 + NADPH mix 10.166 8.773 - NADPH mix 9.566 n.a. 57 + NADPH mix 10.482 5.812 + NADPH mix 9.237 5.663 - NADPH mix 9.439 n.a. 67 + NADPH mix 9.185 8.637 + NADPH mix 9.321 10.313 - NADPH mix 8.555 0.041 8 + NADPH mix 10.123 14.048 + NADPH mix 10.395 11.26 - NADPH mix 8.227 n.a. 18 + NADPH mix 9.534 9.63 + NADPH mix 9.641 8.353 - NADPH mix 7.802 n.a. 28 + NADPH mix 10.422 10.021 + NADPH mix 10.894 12.138 - NADPH mix 7.384 n.a. 38 + NADPH mix 9.189 3.667 + NADPH mix 8.998 3.925 - NADPH mix 8.56 n.a. 48 + NADPH mix 10.497 11.218 + NADPH mix 10.009 9.378 - NADPH mix 8.178 0.01 58 + NADPH mix 8.418 4.05 + NADPH mix 9.913 4.887 - NADPH mix 8.293 n.a. 68 + NADPH mix 9.401 6.674 + NADPH mix 10.176 6.558 - NADPH mix 8.704 n.a. 9 + NADPH mix 8.909 7.488 + NADPH mix 9.904 10.247 - NADPH mix 7.036 n.a. 19 + NADPH mix 6.336 5.573 + NADPH mix 8.809 7.57 - NADPH mix 6.461 n.a. 29 + NADPH mix 6.725 5.613 + NADPH mix 9.786 7.53 - NADPH mix 4.961 0.002 |jg 27 OH formed 0.265 0.256 0.001 0.411 0.346 0.000 0.277 0.252 0.002 0.402 0.387 0.002 0.328 0.367 0.000 0.311 0.300 0.000 0.389 0.374 0.001 0.314 0.306 0.000 0.363 0.431 0.000 0.277 0.307 0.000 0.470 0.553 0.002 0.694 0.542 0.000 0.505 0.433 0.000 0.481 0.557 0.000 0.200 0.218 0.000 0.534 0.468 0.001 0.241 0.246 0.000 0.355 0.322 0.000 0.420 0.517 0.000 0.440 0.430 0.000 0.417 0.385 0.000 27- hydroxylase activity (nmol/h/mg protein) 4.792 6.991 4.846 7.244 6.422 5.647 7.026 5.725 7.341 5.392 9.408 11.412 8.666 9.586 3.858 9.251 4.499 6.255 8.660 8.031 7.405 Page A152 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Mouse energy generating area 20 OH area 27OH ^g 27 OH formed 27- hydroxylase activity mix added (nmol/h/mg protein) 39 + NADPH mix 8.832 4.203 0.238 4.380 + NADPH mix 9.279 4.385 0.236 - NADPH mix 8.084 n.a. 0.000 49 + NADPH mix 9.633 6.413 0.333 6.010 + NADPH mix 11.234 7.141 0.318 - NADPH mix 7.927 n.a. 0.000 59 + NADPH mix 9.799 4.515 0.230 4.419 +- NNAADDPPHH mmiixx 99..509877 4n.7.a6.1 00..204080 69 + NADPH mix 9.836 6.674 0.339 6.322 + NADPH mix 9.96 6.877 0.345 - NADPH mix 1.235 n.a. 0.000 10 + NADPH mix 9.549 8.229 0.431 8.204 + NADPH mix 10.004 9.15 0.457 - NADPH mix 7.526 n.a. 0.000 20 + NADPH mix 9.543 7.346 0.385 7.331 +- NNAADDPPHH mmiixx 98..001098 70..043414 00..401032 40 + NADPH mix 7.696 2.057 0.134 2.390 + NADPH mix 8.096 2.046 0.126 - NADPH mix 7.695 0.01 0.001 60 + NADPH mix 8.639 3.465 0.201 3.828 + NADPH mix 8.551 3.757 0.220 - NADPH mix 8.104 0.047 0.003 30 + NADPH mix 8.271 5.462 0.330 6.184 +- NNAADDPPHH mmiixx 87..470668 5n.7.a0.4 00..303090 50 + NADPH mix 9.353 8.537 0.456 7.941 + NADPH mix 9.445 7.619 0.403 - NADPH mix 7.913 n.a. 0.000 70 + NADPH mix 9.568 4.626 0.242 4.849 + NADPH mix 8.325 4.716 0.283 - NADPH mix 7.941 n.a. 0.000 Page A153 of A172 Appendix to TNO-report of 3M-02 Final version G roup 1 1 1 1 1 1 1 1 1 1 AVERAGE SD 2 2 2 2 2 2 2 2 2 2 AVERAGE SD 3 3 3 3 3 3 3 3 3 3 AVERAGE SD 4 4 4 4 4 4 4 4 4 4 AVERAGE SD 5 5 5 5 5 5 5 5 5 5 AVERAGE SD 6 6 6 6 6 6 6 6 6 6 AVERAGE SD 7 7 7 7 7 7 7 7 7 7 AVERAGE SD M ouse# 1 2 3 4 5 6 7 8 9 10 m ouse# 1 2 3 4 5 6 7 8 9 10 liver w e ight (g) 2 .1 9 2 .0 0 1.66 1.41 1.68 1.70 1.61 1.77 1.68 1.49 average mg m ito ch o n d ria /g liver 14.28 14.28 14.28 14.28 14.28 14.28 14.28 14.28 14.28 14.28 11 11 12 12 13 13 14 14 15 15 16 16 17 17 18 18 19 19 20 20 2.77 1.17 1.88 2 .5 3 1.68 1.23 1.35 1.84 1.53 1.98 14.28 14.28 14.28 14.28 14.28 14.28 14.28 14.28 14.28 14.28 21 21 22 22 23 23 24 24 25 25 26 26 27 27 28 28 29 29 30 30 2 .0 0 2 .2 3 2.27 1.68 1.56 2 .0 6 1.85 1.51 2.42 2 .1 4 14.28 14.28 14.28 14.28 14.28 14.28 14.28 14.28 14.28 14.28 31 31 32 32 33 33 34 34 35 35 36 36 37 37 38 38 39 39 40 40 3 .4 6 3 .6 8 3 .6 9 3 .9 3 4 .2 3 1.94 3.62 3 .9 0 4 .0 3 3 .3 9 2 4 .4 5 2 4 .4 5 2 4 .4 5 2 4 .4 5 2 4 .4 5 2 4 .4 5 2 4 .4 5 2 4 .4 5 2 4 .4 5 2 4 .4 5 41 41 42 42 43 43 44 44 45 45 46 46 47 47 48 48 49 49 50 50 1.90 1.71 2 .4 8 1.69 2 .2 5 2 .4 6 1.47 1.88 1.82 2 .1 4 14.28 14.28 14.28 14.28 14.28 14.28 14.28 14.28 14.28 14.28 51 51 52 52 53 53 54 54 55 55 56 56 57 57 58 58 59 59 60 60 3 .9 0 4.87 4 .1 0 4.17 4 .1 3 3 .4 8 3 .1 3 4.11 4 .7 4 4 .3 3 17.97 17.97 17.97 17.97 17.97 17.97 17.97 17.97 17.97 17.97 61 61 62 62 63 63 64 64 65 65 66 66 67 67 68 68 69 69 70 70 4 .2 9 4 .3 3 3 .8 8 4 .2 8 4 .1 5 3 .8 5 3.91 3 .8 3 3 .3 3 3.92 17.97 17.97 17.97 17.97 17.97 17.97 17.97 17.97 17.97 17.97 cholestero l 27 hydroxylase a ctivity I (n m o l/h /m g protein) per liver (nm o l/h) 11.66 11.41 13.57 3 6 4 .7 3 2 5 .9 3 2 1 .8 10.96 7.50 2 2 0 .8 1 8 0 .0 10.27 6.42 11.41 8.66 8.20 2 4 9 .4 147.7 2 8 8 .5 2 0 7 .8 1 7 4 .6 10.01 2.22 248.1 7 3 .9 6.92 2 7 3 .8 1.77 15.33 11.77 2 9 .5 4 1 1 .7 4 2 5 .2 7.37 5.65 11.21 8.67 1 7 6 .8 99.2 216.1 2 2 7 .8 8.03 7.33 1 7 5 .5 2 0 7 .3 8.40 3.70 2 2 4 .3 123.2 14.18 13.69 13.48 10.40 405.1 4 3 6 .0 437.1 2 4 9 .5 6.62 7.75 1 4 7 .5 2 2 7 .9 7.03 9.59 7.40 6.18 1 8 5 .6 2 0 6 .8 2 5 5 .9 1 8 9 .0 9.63 3.14 2 7 4 .0 1 0 9 .9 8.72 8.27 7.55 5.05 7 3 7 .3 7 4 3 .8 681.1 4 8 5 .2 4.71 4.79 4 8 7 .5 2 2 7 .3 5.72 3.86 4.38 2.39 5 0 6 .7 3 6 7 .9 4 3 1 .6 198.1 5.54 2.03 4 8 6 .7 1 9 2 .9 4.61 10.93 10.45 125.1 2 6 7 .0 3 7 0 .2 6.99 13.31 1 6 8 .8 4 2 7 .6 13.65 7.34 9.25 6.01 7.94 4 7 9 .8 154.1 2 4 8 .4 156.2 2 4 2 .7 9.05 3.02 2 6 4 .0 1 2 3 .5 9.65 6 7 6 .0 9.01 5.75 6.30 5.75 7 8 8 .2 4 2 3 .5 4 7 1 .8 4 2 6 .6 4.85 5.39 3 0 3 .0 3 0 3 .3 4.50 4.42 3.83 3 3 2 .3 3 7 6 .4 2 9 7 .8 5.94 1.93 4 3 9 .9 167.2 10.66 8 2 1 .5 6.39 6.46 6.98 6.76 7.24 9.41 497.1 4 5 0 .3 5 3 6 .5 5 0 4 .0 501.1 6 6 1 .0 6.25 6.32 4.85 4 3 0 .5 3 7 8 .3 3 4 1 .6 7.13 1.68 5 1 2 .2 1 4 0 .0 04-12-2006 Page A154 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 mitochondria; mgpergliverand27-hydroxylaseactivity, pvaluesMann-WhitneyU-test mitochondria mg/gliver group1 vs2 group1vs3 group1vs4 group1vs5 group1 vs6 group1vs7 group2vs3 nn 10 10 0.1p65 n 10 n 10 0.4p36 n 10 n 10 I 0.002 nn 10 10 0.7E96 n 0.0p43 n 10 n 10 0.0p19 n 10 n 10 0.0p05 27hydroxylaseact. 10 10 0.247 10 10 0.631 10 10 0.003 10 10 0.353 0.001 10 10 0.004 10 10 0.579 27hydroxylaseact. perliver 10 10 0.579 10 10 0.684 10 10 0.001 10 10 0.971 10 0.002 10 10 <0.001 10 10 0.353 mitochondria mg/gliver group2vs4 group2vs5 group2vs6 group2vs7 group3vs4 group3vs5 group3vs6 n 10 n 10 <0.p001 n 10 n 10 0.0p75 n 10 n 10 <0.p001 n 10 n 10 <0.p001 n 10 n 10 p 0.002 n 10 n 10 0.2p18 n 10 n 10 0.1p23 27hydroxylaseact. 10 10 0.075 10 10 0.796 10 10 0.063 10 10 0.165 10 10 0.005 10 10 0.684 10 10 0.003 27hydroxylaseact. perliver 10 10 0.003 10 10 0.631 10 10 0.002 10 10 <0.001 10 10 0.015 10 10 0.739 10 10 0.019 mitochondria mg/gliver group3vs7 group4vs5 1 group4vs6 | group4vs7 group5vs6 group5vs7 group6vs7 n 10 n 10 0.0p52 n 10 n 10 p 0.001 n 10 n 10 0.0p09 n 10 n 10 p 0.011 nn 10 10 p 0.011 n 10 n 10 0.0p05 n 10 n 10 0.7p39 27hydroxylaseact. 10 10 0.043 10 10 0.015 10 10 0.529 10 10 0.075 10 10 0.019 10 10 0.123 10 10 0.035 27hydroxylaseact. perliver 10 10 0.001 10 10 0.009 10 10 0.393 10 10 0.796 10 10 0.009 10 10 <0.001 10 10 0.089 p<005 Page A155 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 I. Measurements in vitro experiment (rat hepatocytes) Experiment 1 Protein concentration determination sample 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 Measured dilution average protein conc protein conc (mg/ml) (mg/ml) 97.5 4 376.2 90.6 119.5 4 490.0 125.5 172.9 4 626.8 140.5 155.8 4 672.2 180.3 167.7 4 689.6 177.1 131.6 4 505.6 121.2 139.7 4 508.4 114.5 257.5 4 944.4 214.7 176 4 702.0 175 155.8 4 594.8 141.6 155.8 4 555.8 122.1 167.7 4 645.0 154.8 129 4 512.4 127.2 136.1 4 555.2 141.5 170.8 4 695.8 177.1 172.9 4 717.2 185.7 168.7 4 648.6 155.6 177.1 4 685.6 165.7 151.9 4 605.6 150.9 188.9 4 744.8 183.5 190.1 4 840.0 229.9 168.7 4 662.8 162.7 167.7 4 650.8 157.7 229.9 4 896.6 218.4 150.9 4 594.2 146.2 127.2 4 521.2 133.4 172.9 4 649.6 151.9 170.8 4 713.0 185.7 170.8 4 697.8 178.1 163.7 4 669.0 170.8 gg protein per well 125.4 163.3 208.9 224.1 229.9 168.5 169.5 314.8 234.0 198.3 185.3 215.0 170.8 185.1 231.9 239.1 216.2 228.5 201.9 248.3 280.0 220.9 216.9 298.9 198.1 173.7 216.5 237.7 232.6 223.0 sample 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 Measured protein conc (mg/ml) 134.3 127.2 149.9 131.6 202.7 195.7 194.1 216.8 188.7 203.7 173.8 161.3 194.1 216.8 188.7 203.8 173.9 161.3 168.6 173.9 140.8 143.8 139.7 144.8 155.1 147.9 162.4 164.4 164.4 160.3 179.2 169.7 198.4 167.6 209.1 195.1 207 216.8 239.9 255.6 241.1 249.9 182.33 132.7 201.6 195.1 212.4 221.2 210.4 193 211.4 243.3 208.1 205.9 239.9 223.4 213.5 211.4 198.4 181.3 129.7 133.7 156.1 181.3 dilution 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 average protein conc (mg/ml) 523.0 563.0 796.8 821.8 784.8 670.2 821.8 785.0 670.4 685.0 569.2 569.0 606.0 653.6 649.4 697.8 732.0 808.4 847.6 991.0 982.0 630.1 793.4 867.2 806.8 909.4 828.0 926.6 849.8 759.4 526.8 674.8 pg protein per well 174.3 187.7 265.6 273.9 261.6 223.4 273.9 261.7 223.5 228.3 189.7 189.7 202.0 217.9 216.5 232.6 244.0 269.5 282.5 330.3 327.3 210.0 264.5 289.1 268.9 303.1 276.0 308.9 283.3 253.1 175.6 224.9 Page A156 of A172 Appendix to TNO-report of 3M-02 Final version s am ple 63 64 63 64 63 64 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 10 7 M easured dilution a ve ra g e protein conc protein co n c (m g/m l) (m g/m l) 171.8 4 729.6 193 146.9 4 575.4 140.8 166.5 4 687.0 177 147.9 4 561.2 132.7 130.7 4 516.8 127.7 135.7 4 563.2 145.9 131.7 4 542.8 139.7 7 7 .6 72.1 4 299.4 153.1 4 626.6 160.2 132.7 4 518.8 126.7 9 6 .4 9 0 .2 4 373.2 118.4 4 487.4 125.3 162.2 4 605.6 140.6 152.9 4 660.8 177.5 165.9 4 682.6 175.4 129.7 4 498.2 119.4 138.7 4 504.0 113.3 261.1 217.1 4 956.4 176.4 4 703.6 175.4 153.9 4 585.2 138.7 154.8 4 549.8 120.1 167.9 4 645.6 154.9 126.1 4 502.8 125.3 133.2 4 547.6 140.6 169 176.1 4 690.2 174.3 4 721.2 186.3 167.9 4 647.6 155.9 176.4 4 682.6 164.9 150 4 598.0 149 188.5 4 745.2 184.1 189.6 4 822.0 2 2 1 .4 166.9 4 657.6 1 6 1 .9 166.9 4 647.6 156.9 230.1 4 897.0 2 1 8 .4 149 4 588.4 145.2 125.3 4 515.2 132.3 172.2 4 648.2 151.9 170.1 4 710.6 185.2 170.1 4 693.0 176.4 1 6 3 .9 4 668.0 170.1 132.3 4 516.8 126.1 148.1 4 557.4 130.6 203.6 4 800.2 196.5 212.1 4 8 1 5 .0 195.4 14 6.2 4 719.2 2 1 3 .4 pg protein pe r w ell 2 4 3 .2 1 9 1 .8 2 2 9 .0 187.1 1 7 2 .3 1 8 7 .7 1 8 0 .9 99.8 2 0 8 .9 1 7 2 .9 1 2 4 .4 1 6 2 .5 2 0 1 .9 2 2 0 .3 2 2 7 .5 166.1 1 6 8 .0 3 1 8 .8 2 3 4 .5 195.1 1 8 3 .3 2 1 5 .2 1 6 7 .6 1 8 2 .5 230.1 2 4 0 .4 2 1 5 .9 2 2 7 .5 1 9 9 .3 2 4 8 .4 2 7 4 .0 2 1 9 .2 2 1 5 .9 2 9 9 .0 196.1 1 7 1 .7 216.1 2 3 6 .9 2 3 1 .0 2 2 2 .7 1 7 2 .3 1 8 5 .8 2 6 6 .7 2 7 1 .7 2 3 9 .7 04-12-2006 Page A157 of A172 Appendix to TNO-report of 3M-02____________ Final version__________________________04-12-2006 Page A158 of A172 sam ple com poun d concentration 1 control 2 control 3 control 4 control 5 control 6 control 7 control 8 control 9 control 10 c o n tro l 11 c o n tro l 12 c o n tro l 13 P FBS 1 pM 14 P FBS 1 pM 15 PFBS 10 pM 16 PFBS 10 pM 17 P F B S 1 0 0 pM 18 P FBS 1 0 0 pM 19 PFH S 1 pM 20 PFH S 1 pM 21 P F H S 10 pM 22 P F H S 10 pM 23 PFHS 100 pM 24 PFHS 100 pM 25 PFOS 1 pM 26 PFOS 1 pM 27 PFO S 10 pM 28 PFO S 10 pM 29 PFO S 100 pM 30 PFO S 100 pM 31 R o s u v a s ta tin 0 .0 0 3 pM 32 R osuvastatin 0.003 pM 33 R osuvastatin 0.03 pM 34 R osuvastatin 0.03 pM 35 R osuvastatin 0.3 pM 36 R osuvastatin 0.3 pM 37 PFBS 1 pM 38 PFBS 1 pM 39 PFBS 10 pM 40 PFBS 10 pM 41 P F B S 1 0 0 pM 42 PFBS 1 0 0 pM 43 PFH S 1 pM 44 PFH S 1 pM 45 PFHS 10 pM 46 PFHS 10 pM 47 PFHS 100 pM 48 PFHS 100 pM 49 PFOS 1 pM 50 PFOS 1 pM 51 P F O S 10 pM 52 PFO S 10 pM 53 PFO S 100 pM 54 PFO S 100 pM l4C L a b e l l4C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C la u ric a cid 14C la u ric a cid 14C la u ric a cid 14C p a lm itic a cid 14C p a lm itic a cid 14C p a lm itic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 3H -c h o le s te ro l 14C -c h o le s te ro l (dpm) (dpm) 12705 12827 7957 10612 11820 12414 14124 8971 12699 15542 11979 14954 12531 17327 11864 16561 11644 15565 14154 7968 12949 14391 7804 6763 15327 14468 11500 11220 14439 13928 18148 17531 12484 10821 13353 10981 15401 13298 14081 16955 14983 15087 13978 14244 14523 14505 16419 13313 18682 9191 13999 14418 13096 11960 14417 13268 12438 8472 12519 9940 13661 6222 14096 5074 12455 1670 12791 2268 14394 624 13181 465 13006 7667 13189 10370 13331 12774 17500 14299 13454 8093 16489 14468 12397 13939 12966 11630 13703 10974 13864 15549 15672 16480 15719 17411 12626 9783 13507 16521 15475 19586 13164 12135 15165 15228 9834 10776 14C -c h o le s te ro l c o rre c te d for recovery (dpm) 16067 21225 26944 16295 24200 24684 35474 35812 34294 14442 15462 12056 19249 19896 24747 24783 22237 21098 22152 30891 25833 26143 25623 29191 17712 26423 23430 23610 17475 20370 11685 9235 3440 4549 1112 905 15124 20172 33678 28718 15432 22511 28846 23012 20546 28773 26978 28417 19878 31380 32470 23650 16636 18155 pg protein 1 2 5 .4 1 6 3 .3 2 0 8 .9 224.1 2 2 9 .9 1 6 8 .5 1 6 9 .5 3 1 4 .8 234 1 9 8 .3 1 8 5 .3 215 1 7 0 .8 185.1 2 3 1 .9 239.1 2 1 6 .2 2 2 8 .5 2 0 1 .9 2 4 8 .3 280 2 2 0 .9 2 1 6 .9 2 9 8 .9 198.1 1 7 3 .7 2 1 6 .5 2 3 7 .7 2 3 2 .6 2 2 3 .0 1 7 4 .3 1 8 7 .7 2 6 5 .6 2 7 3 .9 2 6 1 .6 2 2 3 .4 2 7 3 .9 2 6 1 .7 2 2 3 .5 2 2 8 .3 1 8 9 .7 1 8 9 .7 202.0 2 1 7 .9 2 1 6 .5 2 3 2 .6 2 4 4 .0 2 6 9 .5 2 8 2 .5 3 3 0 .3 3 2 7 .3 210.0 2 6 4 .5 289.1 14C -c h o le s te ro l per mg protein (dpm /m g) 128130 129974 128982 72713 105265 146495 209286 113761 146556 72832 83441 56077 112700 107486 106714 103650 102856 92331 109717 124411 92261 118349 118134 97661 89408 152118 108220 99328 75127 91345 67038 49200 12951 16608 4251 4051 55216 77079 150685 125790 81351 118664 142802 105606 94899 123702 110564 105442 70366 95004 99207 112617 62898 62797 A v e ra g e 14C -c h o le s te ro l per m g protein (dpm /m g) 129029 108158 156534 70783 110093 105182 97594 117064 105305 107898 120763 103774 83236 58119 14780 4151 66147 138237 100007 124204 109301 108003 82685 105912 62847 % o f control A verage % o f control 9 9 100 101 100 67 100 97 135 134 100 73 94 103 100 118 79 87 85 83 83 82 80 80 76 72 8 5 91 96 72 82 92 92 84 76 69 94 118 84 80 77 58 65 71 52 45 38 10 11 13 33 3 51 61 71 139 128 116 75 92 110 132 115 98 88 101 114 102 100 97 65 76 88 92 98 104 58 58 58 SD 0.7 34.2 31.0 19.5 2.9 1.7 5.8 8.1 14.3 11.2 34.4 4.9 8.9 9.8 2.0 0.1 14.3 16.3 24.4 24.3 18.8 3.3 16.1 8.8 0.1 0 1 o CD C/J II (-D\ O C/) r3+ 3" CD C/) 5'C/)" -\ 0) CD "D o0i )i 0 VC 1I CD C/) Appendix to TNO-report of 3M-02____________ Final version__________________________04-12-2006 Page A159 of A172 sam ple 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 co m p o u n d conce ntration R osuvastatin 0.003 pM R osuvastatin 0.003 pM R o suvastatin 0.03 pM R o suvastatin 0.03 pM R osuvastatin 0.3 pM R osuvastatin 0.3 pM PFBS 1 pM PFBS 1 pM P FBS 10 pM P FBS 10 pM PFBS 100 pM PFBS 100 pM PFHS 1 pM PFHS 1 pM PFHS 10 pM PFHS 10 pM PFHS 1 0 0 pM PFHS 1 0 0 pM PFO S 1 pM PFO S 1 pM PFO S 1 0 pM PFO S 1 0 pM PFO S 100 pM PFO S 100 pM R osuvastatin 0.003 pM R osuvastatin 0.003 pM R o suvastatin 0.03 pM R o suvastatin 0.03 pM R osuvastatin 0.3 pM R osuvastatin 0.3 pM PFBS 1 pM PFBS 1 pM P FBS 10 pM P FBS 10 pM PFBS 100 pM PFBS 100 pM PFHS 1 pM PFHS 1 pM PFHS 10 pM PFHS 10 pM PFHS 1 0 0 pM PFHS 1 0 0 pM PFO S 1 pM PFO S 1 pM PFO S 10 pM PFO S 1 0 pM PFO S 100 pM PFO S 100 pM R osuvastatin 0.003 pM R osuvastatin 0.003 pM R o suvastatin 0.03 pM R o suvastatin 0.03 pM R osuvastatin 0.3 pM 14C L a b e l l4C b u ty ric a c id l4C b u ty ric a c id 14C b u ty ric a c id 14C b u ty ric a c id 14C b u ty ric a c id 14C b u ty ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C p a lm itic a c id in p u t 3H c h o le s te ro l in p u t 3H c h o le s te ro l in put H cholestero l a v e ra g e in p u t 3H c h o le s te ro l 3H -c h o le s te ro l (dpm ) 15609 15687 14378 13730 15870 12832 13019 16614 16141 15873 17295 16841 10210 15012 15875 16131 16397 14452 15496 17004 13663 13951 14919 16126 15126 15117 15845 15353 16583 15158 14410 15961 16275 14927 14899 2959 14864 15988 14366 15716 13749 16009 14012 15284 14474 12042 14571 13686 13478 13285 12506 13476 14963 26014 25923 25028 25655 14C -c h o le s te ro l (dpm ) 4123 4793 901 984 311 512 11827 19187 21002 19906 21050 16813 11716 18465 17804 20213 12748 11356 14299 17756 13984 16405 11557 12122 4914 5462 1201 1756 465 505 5450 5718 5596 5781 5367 1505 6675 4773 5602 8024 5977 5872 4048 9125 5125 5104 4478 4542 3476 2874 1940 1859 1145 14C - c h o le s te ro l c o rre c te d fo r recovery (dpm ) 6777 7839 1608 1839 503 1024 23306 29628 33381 32173 31225 25612 29439 31556 28772 32147 19946 20159 23673 26790 26258 30168 19874 19285 8335 9270 1945 2934 719 855 9703 9191 8821 9936 9242 13049 11521 7659 10004 13098 11153 9410 7412 15317 9084 10874 7884 8514 6616 5550 3980 3539 1963 pg protein 2 6 8 .9 3 0 3 .1 2 7 6 .0 3 0 8 .9 2 8 3 .3 2 5 3 .1 1 7 5 .6 2 2 4 .9 2 4 3 .2 1 9 1 .8 2 2 9 .0 187.1 1 7 2 .3 1 8 7 .7 1 8 0 .9 99.8 2 0 8 .9 1 7 2 .9 1 2 4 .4 1 6 2 .5 2 0 1 .9 2 2 0 .3 2 2 7 .5 166.1 1 6 8 .0 3 1 8 .8 2 3 4 .5 195.1 1 8 3 .3 2 1 5 .2 1 6 7 .6 1 8 2 .5 2 3 0 .1 2 4 0 .4 2 1 5 .9 2 2 8 .5 1 9 9 .3 2 4 8 .4 2 7 4 .0 2 1 9 .2 2 1 5 .9 2 9 9 .0 196.1 1 7 1 .7 2 1 6 .1 2 3 6 .9 2 3 1 .0 2 2 2 .7 1 7 2 .3 1 8 5 .8 2 6 6 .7 2 7 1 .7 2 3 9 .7 14C -c h o le s te ro l per m g protein (d p m /m g ) 25201 25861 5825 5952 1775 4044 132722 131739 137258 167745 136354 136891 170860 168120 159051 322115 95480 116594 190300 164859 130053 136939 87357 116105 49611 29076 8292 15040 3925 3972 57894 50361 38336 41330 42805 57105 57807 30833 36511 59756 51657 31472 37795 89207 42036 45901 34131 38232 38401 29871 14922 13026 8190 A v e r a g e 14C -c h o le s te ro l per m g protein (dpm /m g) 25531 5889 2910 132231 152501 136623 168120 240583 106037 177579 133496 101731 39343 11666 3948 54127 39833 42805 44320 48134 41565 63501 43968 36182 34136 13974 8190 % o f control Average % o f control 23 24 24 55 6 23 4 85 84 84 88 97 107 87 87 87 109 108 107 102 154 206 61 68 74 122 113 105 83 85 87 56 65 74 32 25 19 57 10 33 3 82 76 71 54 56 58 6 0 71 81 82 63 44 52 68 84 73 59 44 53 90 126 59 62 65 4 8 51 54 54 48 42 21 20 18 12 12 Appendix to TNO-report of 3M-02 Experiment 2 Final version 04-12-2006 Protein concentration determination sample 1 2 3 4 5 6 7 8 9 10 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 Measured protein conc (mg/ml) 191.5 204.6 218.1 230.3 234.8 221 267.6 215.2 187.7 214.2 222.9 233.8 235.8 266.6 250 260.3 232.8 241.9 246.9 269.7 211.4 195.2 155.9 154.1 123.5 172.1 156.8 231.8 139.1 114.9 147 194.3 256.2 220.1 126.6 143.5 221 217.1 158.6 179.4 235.8 224.9 175.8 241.8 196.3 204.6 206.6 200.8 240.8 242.9 190.5 191.5 150.6 154.1 142.6 140.9 dilution 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 average protein conc (mg/ml) 792.2 896.8 911.6 965.6 803.8 913.4 1004.8 1020.6 949.4 1033.2 813.2 620.0 591.2 777.2 508.0 682.6 952.6 540.2 876.2 676.0 921.4 835.2 801.8 814.8 967.4 764.0 609.4 567.0 pg protein per well 264.1 298.9 303.9 321.9 267.9 304.5 334.9 340.2 316.5 344.4 271.1 206.7 197.1 259.1 169.3 227.5 317.5 180.1 292.1 225.3 307.1 278.4 267.3 271.6 322.5 254.7 203.1 189.0 sample 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 Measured protein conc (mg/ml) 231.9 240.9 211.3 208.5 216.2 239.8 203.7 235.8 292.4 340.6 167.6 197.1 177.5 211.3 237.4 232.4 217.3 244.9 202.1 206.2 240 266.7 181.8 202.9 217.3 223.1 188.5 174.1 238.2 250 173.3 204.6 235.8 231.6 229.9 240 183.5 188.5 163.1 152 202.9 228.1 213.8 244.9 211.4 218.1 168.2 149.4 211.4 213 232.4 254.2 245.8 224 156.2 136.5 215.6 236.6 133.9 158.7 210.5 209.7 156.2 184.3 dilution 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 average protein conc (mg/ml) 945.6 839.6 912.0 879.0 1266.0 729.4 777.6 939.6 924.4 816.6 1013.4 769.4 880.8 725.2 976.4 755.8 934.8 939.8 744.0 630.2 862.0 917.4 859.0 635.2 848.8 973.2 939.6 585.4 904.4 585.2 840.4 681.0 pg protein per well 315.2 279.9 304.0 293.0 422.0 243.1 259.2 313.2 308.1 272.2 337.8 256.5 293.6 241.7 325.5 251.9 311.6 313.3 248.0 210.1 287.3 305.8 286.3 211.7 282.9 324.4 313.2 195.1 301.5 195.1 280.1 227.0 Page A160 of A172 Appendix to TNO-report of 3M-02 Final version sam ple 63 64 63 64 63 64 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 M easured protein conc (m g/m l) 252.5 225.7 153.6 142.5 228.2 210.5 228.1 204.6 220.6 244.2 133.9 150.2 220.6 224.8 234.9 236.6 247.5 230.7 137.3 156.4 206.2 194.7 150 175 152.7 142.8 141.9 140.1 230.3 233.8 237.3 211.6 184 146.9 118.4 200.1 180.4 235.6 162.6 132 211.6 252.4 168.8 170.6 222.3 242.6 257.7 247.1 223.1 208.9 178.7 215.1 179.6 194.7 168.8 142.9 188.5 222.3 196.5 180.4 226.7 240.9 182.2 228.4 240 165.2 142.8 272.7 243.5 201.8 167.1 213.4 236.5 254.2 219.6 153.6 122 232 281.5 207.2 227.6 208.1 207.2 192.9 161.7 281.6 218.7 145.5 151.8 162.6 137.4 dilution 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 average protein conc (m g/m l) 252 256 252 256 252 256 276 280 284 288 292 296 300 304 308 312 316 320 324 328 332 336 340 344 348 352 356 360 364 368 372 376 380 384 388 392 396 400 404 408 412 416 420 424 428 432 [jg protein per well 84.0 85.3 84.0 85.3 84.0 85.3 92.0 93.3 94.7 96.0 97.3 98.7 100.0 101.3 102.7 104.0 105.3 106.7 108.0 109.3 110.7 112.0 113.3 114.7 116.0 117.3 118.7 120.0 121.3 122.7 124.0 125.3 126.7 128.0 129.3 130.7 132.0 133.3 134.7 136.0 137.3 138.7 140.0 141.3 142.7 144.0 04-12-2006 Page A161 of A172 Appendix to TNO-report of 3M-02____________ Final version__________________________04-12-2006 Page A162 of A172 sam ple com pound concentration 1 control 2 control 3 control 4 control 5 control 6 control 7 control 8 control 9 control 13 P F B S 1 |j M 14 P FB S 1 j M 15 P FB S 10 j M 16 P FB S 10 j M 17 P F B S 100 j M 18 P FB S 100 j M 19 P FH S 1 j M 20 P F H S 1 j M 21 P F H S 10 j M 22 P F H S 10 j M 23 PFHS 100 j M 24 PFHS 100 j M 25 PFOS 1 j M 26 PFOS 1 j M 27 P F O S 1 0 j M 28 P F O S 1 0 j M 29 PFO S 100 j M 30 PFO S 100 j M 31 R o s u v a s ta tin 0 .0 0 3 j M 32 R osuvastatin 0.003 j M 33 R osuvastatin 0.03 j M 34 R osuvastatin 0.03 j M 35 R osuvastatin 0.3 j M 36 R osuvastatin 0.3 j M 37 PFBS 1 j M 38 PFBS 1 j M 39 PFBS 10 j M 40 PFBS 10 j M 41 P F B S 1 0 0 j M 42 PFBS 100 j M 43 PFHS 1 j M 44 PFHS 1 j M 45 PFHS 10 j M 46 PFHS 10 j M 47 PFH S 100 j M 48 PFHS 100 j M 49 PFOS 1 j M 50 PFOS 1 j M 51 P F O S 1 0 j M 52 P F O S 1 0 j M 53 PFO S 100 j M 54 PFO S 100 j M l4C L a b e l l4C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C la u ric a cid 14C la u ric a cid 14C la u ric a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C a c e tic a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 14C b u ty ric a cid 3H -c h o le s te ro l 14C -c h o le s te ro l (dpm ) (dpm ) 10176 13013 15067 29921 8013 20565 7102 3628 13239 16182 7313 13946 11285 19393 9341 14887 14585 19635 10415 15531 11106 22304 13209 31195 17775 41007 11729 24081 16244 42002 15747 34491 13331 30717 15569 28923 8199 21682 15486 25911 14084 36299 15835 30330 16929 46461 15411 37008 9454 20098 15895 26782 17054 29629 18199 16110 17403 11966 16235 3127 14014 1836 15647 9439 499 439 17104 8190 16962 23749 16583 11608 15691 16193 14615 17212 16380 17173 16700 12743 15447 20907 15347 18404 15658 22910 16797 19524 16476 25363 14120 11804 13621 21880 16279 28289 16347 17820 15609 18990 16385 28115 14C -c h o le s te ro l c o rre c te d for recovery (dpm ) 34516 53601 69272 13788 14910 23262 46384 43017 36337 40250 54206 63744 62269 55416 69791 59120 62193 50143 71378 45162 69565 51699 74077 64817 57380 45479 46894 23893 18559 5199 3536 861 1255 12924 37791 18894 27855 31788 28298 20596 36532 32368 39492 31373 41550 24616 43357 46904 29423 32838 46314 j g protein 264.1 2 9 8 .9 3 0 3 .9 3 2 1 .9 2 6 7 .9 3 0 4 .5 3 3 4 .9 3 4 0 .2 3 1 6 .5 271.1 2 0 6 .7 197.1 259.1 1 6 9 .3 2 2 7 .5 3 1 7 .5 180.1 292.1 2 2 5 .3 307.1 2 7 8 .4 2 6 7 .3 2 7 1 .6 3 2 2 .5 2 5 4 .7 203.1 1 8 9 .0 3 1 5 .2 2 7 9 .9 3 0 4 .0 2 9 3 .0 4 2 2 .0 243.1 2 5 9 .2 3 1 3 .2 308.1 2 7 2 .2 3 3 7 .8 2 5 6 .5 2 9 3 .6 2 4 1 .7 3 2 5 .5 2 5 1 .9 3 1 1 .6 3 1 3 .3 2 4 8 .0 210.1 2 8 7 .3 3 0 5 .8 2 8 6 .3 2 1 1 .7 14C -c h o le s te ro l per mg protein (dpm /m g) 130711 179328 227969 42839 55647 76402 138487 126446 114821 148487 262288 323464 240359 327262 306730 186184 345324 171682 316765 147042 249876 193434 272742 201004 225315 223922 248115 75803 66313 17101 12069 2040 5163 49863 120662 61317 102332 94102 110338 70149 151125 99450 156757 100685 132635 99258 206398 163241 96218 114684 218739 A v e ra g e 14C -c h o le s te ro l per mg protein (dpm /m g) 179336 58296 126585 205388 281912 316996 265754 244224 198459 233088 213159 236019 71058 14585 3601 85262 81825 102220 110637 128104 116660 152828 129729 166712 % o f control Average % o f control 73 100 100 127 73 100 95 131 83 146 180 134 182 171 104 193 96 177 82 139 108 152 112 126 125 138 42 37 10 7 1 3 86 207 105 176 161 189 120 259 171 269 173 228 170 354 280 165 197 375 115 157 177 148 136 111 130 119 132 40 8 2 146 140 175 190 220 200 262 223 286 SD 27.1 29.1 4 4 .9 3 2 .8 8.1 62.7 57.2 4 0 .5 3 1 .3 9.6 9.5 3.7 2.0 1.2 85.9 49.8 19.7 98.2 6 9 .5 3 8 .8 1 3 0 .0 8 1 .3 126.2 0 1 o CD CI/JI (-D\ O C/) r3+ 3" CD C/) 5'C/)" -\ 0) CD "D 0io)i 0 V1CI CD C/) Appendix to TNO-report of 3M-02____________ Final version__________________________04-12-2006 Page A163 of A172 sa m p le co m p o u n d co n c e n tra tio n 14C L a b e l 3H - c h o le s te ro l 14C - c h o le s te ro l (dpm ) (dpm ) 55 R osuvastatin 0.003 uM 56 R osuvastatin 0.003 uM 57 R o suvastatin 0.03 uM 58 R o suvastatin 0.03 pM l4C b u ty ric a c id l4C b u ty ric a c id 14C b u ty ric a c id 14C b u ty ric a c id 16224 16103 16808 17593 4328 5533 975 1781 59 R osuvastatin 0.3 uM 14C b u ty ric a c id 14906 452 60 R osuvastatin 0.3 uM 61 P F B S 1 uM 14C b u ty ric a c id 14C la u ric a c id 15758 14491 284 19019 62 PFBS 1 uM 63 PFBS 10 uM 14C la u ric a c id 14C la u ric a c id 17266 16567 28110 21487 64 PFBS 10 uM 65 P F B S 100 uM 14C la u ric a c id 14C la u ric a c id 17868 17520 19412 21648 66 P F B S 100 uM 67 PFH S 1 uM 14C la u ric a c id 14C la u ric a c id 19364 16638 28972 26282 68 PFH S 1 uM 69 PFH S 10 uM 70 PFH S 10 uM 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 17741 17115 16449 30159 25762 23842 71 P F H S 10 0 uM 72 P FH S 100 uM 73 PFO S 1 uM 74 PFO S 1 uM 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 15800 16793 16050 17035 21356 27449 18811 24894 75 PFO S 10 uM 76 PFO S 10 uM 77 PFO S 100 uM 78 PFO S 100 uM 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 16660 15663 16046 13213 16687 19295 27259 24544 79 R osuvastatin 0.003 uM 80 R osuvastatin 0.003 uM 81 R o s u v a s ta tin 0 .0 3 uM 82 R o suvastatin 0.03 uM 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 14C la u ric a c id 13776 12989 15098 11184 6081 3529 1767 2114 83 R osuvastatin 0.3 uM 84 R osuvastatin 0.3 uM 14C la u ric a c id 14C la u ric a c id in p u t 3H c h o le s te ro l 13447 14569 26701 566 329 in p u t 3H c h o le s te ro l in p u t 3H c h o le s te ro l 1 a v e r a g e in p u t 3H c h o le s te ro l 27378 26895 269 91.3 3333 14C - c h o le s te ro l c o r re c te d fo r recovery (dpm ) 7200 9274 1566 2732 818 486 38645 43943 35007 29324 33351 40384 42637 45884 40628 39123 36483 44119 31635 39444 27035 33250 45853 50138 11915 7333 3159 5102 1136 610 ug protein 2 8 2 .9 3 2 4 .4 3 1 3 .2 1 9 5 .1 3 0 1 .5 1 9 5 .1 2 8 0 .1 2 2 7 .0 3 1 8 .8 1 9 7 .4 2 9 2 .5 2 8 8 .5 3 0 9 .9 1 8 9 .4 2 9 6 .9 3 1 4 .3 3 1 8 .8 1 9 5 .8 2 6 7 .3 2 1 6 .7 1 9 7 .0 1 8 8 .0 3 0 9 .4 2 9 9 .3 2 2 0 .6 2 1 2 .3 2 7 7 .3 1 9 6 .4 3 0 9 .3 2 2 6 .3 14C - c h o le s te ro l pe r m g p rotein (d pm /m g) 25449 28589 4999 14003 2715 2494 137952 193583 109809 148550 114033 139995 137582 242261 136826 124462 114438 225325 118363 182048 137234 176863 148200 167537 54010 34537 11390 25977 3673 2694 A v e ra g e 14C - c h o le s te ro l pe r m g pro te in (d pm /m g) 27019 9501 2604 165768 129179 127014 168120 130644 169881 150205 157048 157868 44273 18684 3183 % of control A verage % of control 44 46 49 9 16 24 54 4 109 131 153 87 102 117 90 100 111 109 150 191 108 103 98 90 134 178 94 119 144 108 124 140 117 125 132 43 35 27 9 15 21 33 2 SD 3.8 10.9 0.3 31.1 2 1 .6 14.5 5 8 .5 6.9 6 1 .9 3 5 .6 22.1 10.8 10.9 8.1 0.5 Appendix to TNO-report of 3M-02 Experiment 3 Final version Protein concentration determination sa m p le 1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 M easured protein conc (m g/m l) 246.35 298.46 229.35 266.32 232.70 299.74 186.54 154.56 143.00 169.33 153.58 301.02 220.50 370.42 222.70 224.91 171.32 272.34 180.40 240.62 227.12 209.66 295.91 248.65 295.91 331.42 268.72 222.71 282.13 236.08 172.33 263.93 175.34 171.32 247.50 249.81 393.62 348.03 289.60 153.58 227.12 209.66 317.98 272.34 211.81 258.00 195.88 304.88 389.03 352.27 258.00 279.67 363.75 295. 9 1 dilution 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 protein conc pg protein (m g/m l) per well 985.4 328.5 1193.8 397.9 917.4 305.8 1065.3 355.1 930.8 310.3 1199.0 399.7 746.2 618.2 248.7 206.1 572.0 190.7 677.3 225.8 614.3 1204.1 204.8 401.4 882.0 294.0 1481.7 493.9 890.8 296.9 899.6 299.9 685.3 228.4 1089.4 363.1 721.6 240.5 962.5 320.8 908.5 302.8 838.6 279.5 1183.6 394.5 994.6 331.5 1183.6 394.5 1325.7 1074.9 441.9 358.3 890.8 296.9 1128.5 376.2 944.3 314.8 689.3 1055.7 229.8 351.9 701.4 233.8 685.3 228.4 990.0 330.0 999.2 333.1 1574.5 524.8 1392.1 464.0 1158.4 386.1 614.3 204.8 908.5 302.8 838.6 279.5 1271.9 424.0 1089.4 363.1 847.2 1032.0 282.4 344.0 783.5 261.2 1219.5 406.5 1556.1 518.7 1409.1 1032.0 469.7 344.0 1118.7 372.9 1455.0 485.0 1183.6 394.5 04-12-2006 Page A164 of A172 Appendix to TNO-report of 3M-02 Final version sample proteiMn ecaosnucre(md g/ml) dilution pro(mtegin/mclo)nc ^gpeprrwoteeliln 56 356.51 4 1426.0 475.3 57 319.45 4 1277.8 425.9 58 356.51 4 1426.0 475.3 59 319.45 4 1277.8 425.9 60 226.01 4 904.0 301.3 61 241.05 4 964.2 321.4 62 333.17 4 1332.7 444.2 63 251.23 4 1004.9 335.0 64 297.09 4 1188.4 396.1 65 232.80 4 931.2 310.4 66 268.15 4 1072.6 357.5 67 294.15 4 1176.6 392.2 68 222.82 4 891.3 297.1 69 295.13 4 1180.5 393.5 70 244.74 4 979.0 326.3 71 237.38 4 949.5 316.5 72 207.61 4 830.4 276.8 73 324.00 4 1296.0 432.0 74 253.09 4 1012.4 337.5 75 241.05 4 964.2 321.4 76 283.46 4 1133.8 377.9 77 267.20 4 1068.8 356.3 78 275.77 4 1103.1 367.7 79 347.64 4 1390.6 463.5 80 216.53 4 866.1 288.7 81 368.75 4 1475.0 491.7 82 219.00 4 876.0 292.0 83 329.09 4 1316.4 438.8 84 221.92 4 887.7 295.9 85 285.39 4 1141.6 380.5 86 348.30 4 1393.2 464.4 87 312.93 4 1251.7 417.2 88 212.95 4 851.8 283.9 89 288.30 4 1153.2 384.4 90 281.53 4 1126.1 375.4 91 305.97 4 1223.9 408.0 92 245.66 4 982.6 327.5 93 274.81 4 1099.2 366.4 94 289.28 4 1157.1 385.7 95 254.03 4 1016.1 338.7 96 230.98 4 923.9 308.0 97 288.30 4 1153.2 384.4 98 332.15 4 1328.6 442.9 99 294.15 4 1176.6 392.2 100 219.22 4 876.9 292.3 101 335.22 4 1340.9 447.0 102 252.16 4 1008.6 336.2 103 297.09 4 1188.4 396.1 104 247.52 4 990.1 330.0 105 280.57 4 1122.3 374.1 106 250.30 4 1001.2 333.7 107 296.11 4 1184.4 394.8 108 217.43 4 869.7 289.9 04-12-2006 Page A165 of A172 Appendix to TNO-report of 3M-02____________ Final version__________________________04-12-2006 Page A166 of A172 3H cholesterol sam ple m ix 11 13 14 15 16 17 18 1 11 1 12 1 13 1 14 1 15 1 16 1 17 1 18 1 19 1 20 1 21 1 22 1 23 1 24 1 25 1 26 1 27 1 28 1 29 1 30 1 31 1 32 1 33 1 34 1 35 1 36 1 37 1 38 1 39 1 41 1 42 1 43 1 44 1 45 1 46 1 47 1 48 1 49 1 50 1 51 1 52 1 53 1 54 1 55 1 56 1 57 1 58 1 59 1 60 com pound concentration control control control control control control control control control PFB S 1 uM PFB S 1 uM PF B S 10 uM PF B S 10 uM PFBS 100 uM PFBS 100 uM P FH S 1 uM P FH S 1 uM PFH S 10 uM PFH S 10 uM P FH S 100 uM P FH S 100 uM PFO S 1 uM PFO S 1 uM P FO S 10 uM P FO S 10 uM P FO S 100 uM P FO S 100 uM R osuvastatin 0.003 uM R osuvastatin 0.003 uM R osuvastatin 0.03 uM R osuvastatin 0.03 uM R osuvastatin 0.3 uM R osuvastatin 0.3 uM PFB S 1 uM PFB S 1 uM PF B S 10 uM PFBS 100 uM PFBS 100 uM P FH S 1 uM P FH S 1 uM PFH S 10 uM PFH S 10 uM P FH S 100 uM P FH S 100 uM PFO S 1 uM PFO S 1 uM P FO S 10 uM P FO S 10 uM P FO S 100 uM P FO S 100 uM R osuvastatin 0.003 uM R osuvastatin 0.003 uM R osuvastatin 0.03 uM R osuvastatin 0.03 uM R osuvastatin 0.3 uM R osuvastatin 0.3 uM l4C L a b e l l4C a c e tic a c id 14C a c e tic a c id 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C la u ric a c id 14C la u ric a c id 14C p a lm itic a c id 14C p a lm itic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 14C b u ty ric acid 3H -c h o le s te ro l (dpm ) 12507 19023 16324 15491 14301 15647 14301 16834 17733 17724 15643 13898 17481 17149 18303 17772 16907 17592 16152 18689 17098 17841 19413 17762 14828 16243 15814 15332 14969 14770 14215 16761 16727 15968 14142 16118 16293 19457 18922 17479 17443 16118 18498 17002 17226 16924 15074 17062 15031 18507 14681 15247 15905 17593 13507 18268 14C -c h o le s te ro l (dpm ) 44451 99078 18935 15714 17937 40817 32511 5000 4789 22246 21849 22496 26287 23557 22881 35195 39844 23683 24871 27769 22118 27624 43559 25533 24114 22967 26323 2953 3029 574 626 257 248 5934 11778 13512 9931 7769 6439 14976 7993 9922 8585 10438 7974 8198 12993 18014 12106 9530 930 687 276 212 94 120 14C -c h o le s te ro l c o rre c te d fo r recovery (dpm ) 91111 133519 29736 26005 32153 66874 58279 7614 6923 32176 35806 41495 38550 35215 32048 50768 60414 34512 39474 38091 33162 39693 57521 36851 41690 36248 42672 4938 5187 996 1129 393 380 9527 21350 21491 15626 10236 8724 21965 11747 15781 11898 15738 11867 12418 22097 27066 20647 13201 1624 1155 445 309 178 168 ug protein 328.5 397.9 305.8 355.1 310.3 399.7 248.7 225.8 204.8 401.4 294.0 493.9 296.9 299.9 228.4 363.1 240.5 320.8 302.8 279.5 394.5 331.5 394.5 441.9 358.3 296.9 376.2 314.8 229.8 351.9 233.8 228.4 330.0 333.1 524.8 464.0 204.8 302.8 279.5 424.0 363.1 282.4 344.0 261.2 406.5 518.7 469.7 344.0 372.9 485.0 394.5 475.3 425.9 475.3 425.9 301.3 14C -c h o le s te ro l per m g protein (dpm /m g) 277384 335520 97240 73233 103632 167329 234314 33725 33809 80168 121789 84018 129826 117430 140298 139810 251169 107571 130352 136259 84052 119725 145791 83394 116357 122069 113436 15686 22576 2831 4829 1721 1152 28602 40681 46312 76307 33802 31206 51807 32351 55879 34586 60261 29192 23940 47045 78680 55370 27218 4116 2430 1044 650 419 559 A v e r a g e '4C - c h o le s te ro l per m g protein (dpm /m g) 306452 91368 200821 33767 100979 106922 128864 195490 118962 110155 132758 99876 117752 19131 3830 1436 34641 46312 55054 41506 44115 47423 26566 62863 41294 3273 847 489 % of control Average SD % of control 90.5 100.0 13.4 109.5 106.4 100.0 17.5 80.2 113.4 83.3 100.0 23.6 116.7 99.9 100.0 0.18 100.1 26.2 33.0 9.6 39.7 27.4 34.9 10.6 42.4 38.3 42.1 5.3 45.8 45.6 63.8 25.7 82.0 35.1 38.8 5.3 42.5 44.5 35.9 12.0 27.4 39.1 43.3 6.0 47.6 27.2 32.6 7.6 38.0 39.8 38.4 2.0 37.0 5.1 6 .2 1.6 7.4 0.9 1.2 0.5 1.6 0 .6 0 .5 0.1 0.4 31.3 37.9 9.3 44.5 50.7 50.7 83.5 60.3 32.9 37.0 34.2 45.4 15.9 56.7 35.4 48.3 18.2 61.2 37.9 51.9 19.9 66.0 32.0 29.1 4.1 26.2 51.5 68.8 24.5 86.1 60.6 45.2 21.8 29.8 4.5 3.6 1.3 2.7 1.1 0 .9 0 .3 0.7 0 .5 0 .5 0.1 0.6 0 1 o CD CI /JI (-D\ O C/) r3+ 3" CD C/) 5'C/)" -\ 0) CD "D 0io)i 0 V1CI CD C/) Appendix to TNO-report of 3M-02____________ Final version__________________________04-12-2006 Page A167 of A172 3H cholesterol sam ple m ix 1 61 1 62 1 63 1 64 1 65 1 66 1 67 1 68 1 69 1 70 1 71 1 72 2 73 2 74 2 75 2 76 2 77 2 78 2 79 2 80 2 81 2 82 2 83 2 85 2 86 2 87 2 88 2 89 2 90 2 91 2 92 2 93 2 94 2 95 2 96 2 97 2 98 2 99 2 100 2 101 2 102 2 103 2 104 2 105 2 106 2 107 2 108 com pound concentration PFBS 1 uM PFBS 1 uM PFBS 10 uM PFBS 10 uM PFBS 100 uM PFBS 100 uM PFHS 1 uM PFHS 1 uM PFH S 10 uM PFH S 10 uM PFHS 100 uM PFHS 100 uM PFOS 1 uM PFOS 1 uM PFO S 10 uM PFO S 10 uM PFO S 100 uM PFO S 100 uM Rosuvastatin 0.003 uM Rosuvastatin 0.003 uM Rosuvastatin 0.03 uM Rosuvastatin 0.03 uM Rosuvastatin 0.3 uM PFBS 1 uM PFBS 1 uM PFBS 10 uM PFBS 10 uM PFBS 100 uM PFBS 100 uM PFHS 1 uM PFHS 1 uM PFH S 10 uM PFH S 10 uM PFHS 100 uM PFHS 100 uM PFOS 1 uM PFOS 1 uM PFO S 10 uM PFO S 10 uM PFO S 100 uM PFO S 100 uM Rosuvastatin 0.003 uM Rosuvastatin 0.003 uM Rosuvastatin 0.03 uM Rosuvastatin 0.03 uM Rosuvastatin 0.3 uM Rosuvastatin 0.3 uM 14C Label 3 H -c h o le s te ro l 14C -c h o le s te ro l (dpm) (dpm) l4C lauric acid 18064 35197 14C la u ric a c id 16312 33843 14C la u ric a c id 16632 31024 14C la u ric a c id 16430 42519 14C la u ric a c id 17140 24245 14C la u ric a c id 16929 22983 14C la u ric a c id 17947 34462 14C la u ric a c id 17680 35488 14C la u ric a c id 17511 31561 14C la u ric a c id 18652 34500 14C la u ric a c id 17842 20913 14C la u ric a c id 17390 30612 14C la u ric a c id 12194 39952 14C la u ric a c id 17125 49945 14C la u ric a c id 16554 29563 14C la u ric a c id 16019 42312 14C la u ric a c id 15880 22742 14C la u ric a c id 17209 31390 14C la u ric a c id 15981 3218 14C la u ric a c id 14109 3171 14C la u ric a c id 17448 754 14C la u ric a c id 16191 686 14C la u ric a c id 15558 261 14C p a lm itic a c id 16555 4312 14C p a lm itic a c id 17040 3219 14C p a lm itic a c id 15827 3366 14C p a lm itic a c id 16659 4602 14C p a lm itic a c id 15285 2953 14C p a lm itic a c id 17337 3284 14C p a lm itic a c id 14572 2399 14C p a lm itic a c id 14708 3322 14C p a lm itic a c id 15562 3238 14C p a lm itic a c id 14849 3857 14C p a lm itic a c id 16477 2952 14C p a lm itic a c id 15761 3697 14C p a lm itic a c id 16923 3859 14C p a lm itic a c id 19055 4608 14C p a lm itic a c id 16210 4074 14C p a lm itic a c id 17729 5568 14C p a lm itic a c id 16090 2981 14C p a lm itic a c id 17458 3072 14C p a lm itic a c id 12554 711 14C p a lm itic a c id 17205 986 14C p a lm itic a c id 16635 534 14C p a lm itic a c id 17350 544 14C p a lm itic a c id 13361 313 14C p a lm itic a c id 15847 m ix 1 359 m ix 2 input 3H cholesterol 25860 24418 input 3H cholesterol input 3H cholesterol 25671 25376 25195 24950 average input 3H cholesterol 2 5 6 3 5 .7 2 4 8 5 4 .3 C -cholesterol corrected fo r recovery (dpm) 49950 53187 47819 66342 36262 34803 49226 51457 46205 47417 30048 45127 81432 72488 44386 65649 35594 45335 5005 5586 1074 1053 417 6474 4695 5286 6866 4802 4708 4092 5614 5171 6456 4453 5830 5668 6010 6247 7806 4605 4373 1408 1424 798 779 582 563 ug protein 3 2 1 .4 4 4 4 .2 3 3 5 .0 396.1 3 1 0 .4 3 5 7 .5 3 9 2 .2 297.1 3 9 3 .5 3 2 6 .3 3 1 6 .5 2 7 6 .8 4 3 2 .0 3 3 7 .5 3 2 1 .4 3 7 7 .9 3 5 6 .3 3 6 7 .7 4 6 3 .5 2 8 8 .7 4 9 1 .7 2 9 2 .0 4 3 8 .8 3 8 0 .5 4 6 4 .4 4 1 7 .2 2 8 3 .9 3 8 4 .4 3 7 5 .4 4 0 8 .0 3 2 7 .5 3 6 6 .4 3 8 5 .7 3 3 8 .7 3 0 8 .0 3 8 4 .4 4 4 2 .9 3 9 2 .2 2 9 2 .3 4 4 7 .0 3 3 6 .2 396.1 3 3 0 .0 374.1 3 3 3 .7 3 9 4 .8 2 8 9 .9 14C -c h o le s te ro l per m g protein (dpm /m g) 155414 119730 142754 167480 116825 97343 125512 173201 117417 145310 94937 163023 188500 214808 138103 173700 99909 123297 10797 19348 2185 3606 950 17013 10110 12669 24182 12492 12542 10030 17139 14114 16738 13147 18930 14744 13572 15927 26705 10302 13008 3554 4316 2133 2335 1475 1942 A v e ra g e 14C -c h o le s te ro l per m g protein (dpm /m g) 137572 155117 107084 168120 131364 128980 201654 155901 111603 15073 2895 1050 13562 18425 42805 13584 15426 16038 14158 21316 11655 3935 2234 8190 % of control Average SD % of control 77.4 68.5 12.6 59.6 71.1 77.2 8.7 83.4 58.2 53.3 6.9 48.5 62.5 74.4 16.8 86.2 58.5 65.4 9.8 72.4 47.3 64.2 24.0 81.2 93.9 100.4 9.3 107.0 68.8 77.6 12.5 86.5 49.8 55.6 8.2 61.4 5.4 7.5 3.0 9.6 1.1 1.4 0.5 1.8 0.5 0.5 0.1 50.4 50.4 37.5 71.6 37.0 37.1 29.7 50.8 41.8 49.6 38.9 56.1 43.7 40.2 47.2 79.1 30.5 38.5 10.5 12.8 6.3 6.9 4.4 5.8 54.6 37.1 40.2 45.7 47.5 41.9 63.1 34.5 11.7 6.6 5.1 24.1 0.1 14.9 5.5 12.1 2.5 22.6 5.7 1.6 0.4 1.0 Appendix to TNO-report of 3M-02 Experiment 4 Final version 04-12-2006 Protein concentration determination sample 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 Measured protein conc (mg/ml) well 1 well 2 207.81 223.77 214.31 224.72 189.73 202.31 205.97 230.5 234.4 252.34 221.86 205.97 218.07 224.72 225.68 225.68 214.31 223.77 210.58 214.31 210.58 220.91 199.58 205.97 212.44 214.31 241.29 245.28 230.5 226.54 234.4 239.31 272.05 262.61 292.63 272.24 254.37 242.28 231.47 237.34 269.94 274.18 272.05 253.35 253.35 250.31 242.28 221.86 202.31 210.58 241.29 242.28 245.28 239.31 230.5 235.37 245.28 233.42 218.07 209.66 250.31 240.3 253.35 242.28 244.28 249.3 233.42 237.34 215.24 204.14 227.6 210.58 249.52 228.83 256.56 246.52 277.1 284.44 248.52 238.6 251.52 254.54 266.75 258.59 238.6 246.52 265.73 254.54 251.52 253.53 242.55 245.53 237.62 229.8 212.56 208.8 211.62 203.19 206.92 209.73 194.87 192.13 206.92 210.68 222.08 234.67 177.7 186.68 214.45 228.83 220.17 214.45 dilution 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 protein conc (mg/ml) 1079.0 1097.6 980.1 1091.2 1216.9 1069.6 1107.0 1128.4 1095.2 1062.2 1078.7 1013.9 1066.9 1216.4 1142.6 1184.3 1336.7 1412.2 1241.6 1172.0 1360.3 1313.5 1259.2 1160.4 1032.2 1208.9 1211.5 1164.7 1196.8 1069.3 1226.5 1239.1 1234.0 1176.9 1048.5 1095.5 1195.9 1257.7 1403.9 1217.8 1265.2 1313.4 1212.8 1300.7 1262.6 1220.2 1168.6 1053.4 1037.0 1041.6 967.5 1044.0 1141.9 911.0 1108.2 1086.6 pg protein per well 359.7 365.9 326.7 363.7 405.6 356.5 369.0 376.1 365.1 354.1 359.6 338.0 355.6 405.5 380.9 394.8 445.6 470.7 413.9 390.7 453.4 437.8 419.7 386.8 344.1 403.0 403.8 388.2 398.9 356.4 408.8 413.0 411.3 392.3 349.5 365.2 398.6 419.2 468.0 405.9 421.7 437.8 404.3 433.6 420.9 406.7 389.5 351.1 345.7 347.2 322.5 348.0 380.6 303.7 369.4 362.2 Page A168 of A172 Appendix to TNO-report of 3M-02 Final version 04-12-2006 sam ple 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 91 92 94 95 96 97 98 100 101 103 104 105 106 107 109 110 112 113 114 115 116 118 119 M easured protein conc (m g/m l) well 1 well 2 224.96 219.21 213.51 199.48 210.68 223.04 218.26 204.12 205.99 204.12 186.68 160.17 209.73 205.99 229.8 237.62 222.08 193.04 161.9 203.19 217.3 225.93 246.52 234.67 261.64 259.6 239.59 278.14 212.61 232.92 225.79 231.13 233.82 225.79 241.03 239.22 217.85 224.02 220.49 283 263.68 235.65 255.55 285.49 215.22 229.35 240.13 233.82 241.03 239.22 238.32 232.03 221.37 234.72 225.79 287.81 208.27 204.81 203.09 218.73 216.10 205.67 224.02 218.73 233.82 226.68 242.85 252.91 242.85 218.73 255.68 242.85 248.32 229.35 251.99 190.32 214.35 217.85 214.35 212.61 203.95 217.85 211.74 224.02 218.73 235.62 239.22 245.58 209.13 256.60 245.58 237.42 242.85 243.76 245.58 231.13 251.07 259.39 217.85 255.68 272.51 291.69 219.61 243.74 255.52 267.47 234.05 216.10 246.67 269.48 271.50 235.01 d ilu tio n 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 protein conc (m g/m l) 1120.0 1093.7 1044.1 1013.7 1037.0 949.3 805.2 1032.3 1058.2 1139.3 1210.4 1141.9 1313.3 1238.1 1237.9 1409.1 1069.6 1155.7 1164.8 1162.4 1187.1 1162.5 1198.4 1178.1 1098.1 1146.9 1115.7 1427.0 996.5 1047.9 1052.4 1082.7 1071.8 1024.1 1104.7 1076.2 1144.6 1113.5 1196.2 1230.3 1221.1 1069.7 1280.7 1221.1 1214.4 1180.5 1239.4 1262.4 1122.5 1266.9 1410.5 1089.3 1226.0 1312.5 1347.4 1172.7 |jg protein per w ell 373.3 364.6 348.0 337.9 345.7 316.4 268.4 344.1 352.7 379.8 403.5 380.6 437.8 412.7 412.6 469.7 356.5 385.2 388.3 387.5 395.7 387.5 399.5 392.7 366.0 382.3 371.9 475.7 332.2 349.3 350.8 360.9 357.3 341.4 368.2 358.7 381.5 371.2 398.7 410.1 407.0 356.6 426.9 407.0 404.8 393.5 413.1 420.8 374.2 422.3 470.2 363.1 408.7 437.5 449.1 390.9 Page A169 of A172 Appendix to TNO-report of 3M-02____________ Final version__________________________04-12-2006 Page A170 of A172 3H cholesterol sam ple m ix 11 12 13 14 15 17 18 19 1 10 1 11 1 12 1 13 1 15 1 17 1 18 1 19 1 20 1 22 1 23 1 24 1 25 1 26 1 27 1 28 1 30 1 31 1 32 1 33 1 34 1 35 1 36 1 38 1 39 2 40 2 41 2 42 2 43 2 44 2 45 2 46 2 47 2 48 2 49 2 50 2 51 2 52 2 53 2 54 2 56 2 57 2 58 com poun d concentration control control control control control control control control control control control P F B S 1 |j M PFBS 1 j M P FB S 10 j M P FB S 10 j M PFBS 100j M PFBS 100j M PFHS 1 j M PFHS 1 j M PFHS 1 j M PFHS 10 j M PFHS 10 j M PFHS 10 j M PFHS 1 00j M PFHS 1 00j M PFOS 1 j M PFOS 1 j M PFOS 1 j M PFO S 10 j M PFO S 10 j M PFO S 10 j M PFO S 100 j M PFO S 100 j M R osuvastatin 0.003 j M R osuvastatin 0.003 j M R osuvastatin 0.003 j M R osuvastatin 0.03 j M R osuvastatin 0.03 j M R osuvastatin 0.03 j M R osuvastatin 0.3 j M R osuvastatin 0.3 j M R osuvastatin 0.3 j M PFBS 1 j M PFBS 1 j M PFBS 1 j M P FB S 10 j M P FB S 10 j M P FB S 10 j M PFBS 100j M PFBS 100j M PFHS 1 j M 14C L a b e l l4C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C b u ty ric a c id 14C b u ty ric a c id 14C b u ty ric a c id 14C p a lm itic a cid 14C p a lm itic a cid 14C p a lm itic a cid 14C p a lm itic a cid 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C a c e tic a c id 14C b u ty ric a c id 14C b u ty ric a c id 14C b u ty ric a c id 14C b u ty ric a c id 14C b u ty ric a c id 14C b u ty ric a c id 14C b u ty ric a c id 14C b u ty ric a c id 14C b u ty ric a c id 3H -c h o le s te ro l 14C -c h o le s te ro l (dpm ) (dpm ) 11557 13921 1815 1877 12789 14330 2094 2430 14143 2257 12409 2888 13395 4007 12206 1142 13316 1694 12616 1574 13307 14019 1703 2569 14018 13123 1506 1714 12859 12350 1837 1427 12583 2709 12002 1811 12074 1822 10469 2089 12178 13070 2935 3091 11021 12494 3398 2059 11696 12079 1924 3650 12015 2929 12687 2772 12477 2383 12560 2407 10462 10416 1828 1647 9390 1807 9534 81 11731 95 12187 61 11494 36 12998 42 10852 18 9480 7 8849 11450 10 12 9541 11879 1216 2158 12114 11350 3192 998 11456 1499 9935 1125 11036 9818 4223 1517 12175 1686 14C -c h o le s te ro l c o rre c te d for recovery (dpm ) 3220 2765 3357 3477 3272 4772 6134 1918 2608 2558 2624 3757 2203 2678 2929 2369 4414 3094 3094 4091 4942 4849 6322 3379 3373 6196 4998 4480 3916 3929 3583 3242 3946 171 163 100 63 65 33 15 23 21 2559 3647 5290 1765 2627 2273 7682 3102 2780 jg protein 3 5 9 .7 3 6 5 .9 3 2 6 .7 3 6 3 .7 4 0 5 .6 3 6 9 .0 376.1 365.1 354.1 3 5 9 .6 3 3 8 .0 3 5 5 .6 3 8 0 .9 4 4 5 .6 4 7 0 .7 4 1 3 .9 3 9 0 .7 4 3 7 .8 4 1 9 .7 3 8 6 .8 344.1 4 0 3 .0 4 0 3 .8 3 8 8 .2 3 5 6 .4 4 0 8 .8 4 1 3 .0 4 1 1 .3 3 9 2 .3 3 4 9 .5 3 6 5 .2 4 1 9 .2 4 6 8 .0 4 0 5 .9 4 2 1 .7 4 3 7 .8 4 0 4 .3 4 3 3 .6 4 2 0 .9 4 0 6 .7 3 8 9 .5 351.1 3 4 5 .7 3 4 7 .2 3 2 2 .5 3 4 8 .0 3 8 0 .6 3 0 3 .7 3 6 2 .2 3 7 3 .3 3 6 4 .6 14C -c h o le s te ro l per m g protein (dpm /m g) 8953 7556 10276 9559 8067 12932 16307 5255 7367 7114 7764 10566 5784 6011 6223 5724 11299 7066 7372 10578 14362 12033 15655 8704 9463 15155 12102 10892 9982 11243 9811 7733 8432 420 386 230 156 150 79 36 58 60 7402 10504 16403 5073 6902 7487 21211 8309 7626 % o f control Average % o f control 9 8 .5 1 0 0 .0 83.2 113.1 105.2 6 4 .9 1 0 0 .0 1 0 4 .0 131.1 7 6 .4 1 0 0 .0 107.2 1 0 3 .5 1 1 2 .9 1 1 6 .3 90.0 63.7 66.2 67.3 6 8 .5 6 3 .0 93.7 1 2 4 .4 7 7 .8 91.8 81.1 1 1 6 .4 158.1 1 5 4 .3 1 3 2 .4 1 7 2 .3 9 5 .8 1 0 0 .0 104.1 1 6 6 .8 1 3 9 .9 133.2 1 1 9 .9 1 0 9 .9 1 1 3 .9 123.7 1 0 8 .0 85.1 89.0 9 2 .8 4.6 3.8 4.2 2.5 1.7 1.4 1.6 0.9 0.4 0.6 0.6 0.7 5 9 .5 92.0 8 4 .5 1 3 1 .9 4 0 .8 52.2 5 5 .5 60.2 1 7 0 .6 1 1 8 .7 6 6 .8 6 1 .3 1 2 4 .5 SD 12.7 3 3 .3 16.2 37.2 1.6 4 3 .4 2 1 .4 20.2 5.9 24.2 8.6 5.4 1.1 0.5 0.1 3 6 .8 10.1 7 3 .4 62.2 0 1 o CD CI /JI (-D\ O C/) r3+ 3" CD C/) 5'C/)" -\ 0) CD "D 0io)i 0 V1CI CD C/) Appendix to TNO-report of 3M-02____________ Final version__________________________04-12-2006 Page A171 of A172 3H cholesterol s a m p le m ix 2 59 2 60 2 61 2 62 2 64 2 66 2 67 2 68 2 69 2 70 2 71 2 72 2 73 2 74 2 75 2 76 2 77 2 78 2 79 2 80 2 81 2 82 2 83 2 85 2 86 2 87 2 88 2 89 2 91 2 92 2 94 2 95 2 96 2 97 2 98 2 100 2 101 2 103 2 104 2 105 2 106 2 107 2 109 2 110 2 112 2 113 2 114 2 115 2 116 2 118 2 119 com p o u n d co n ce n tra tio n PFH S 1 pM PFH S 1 pM P F H S 1 0 pM P F H S 1 0 pM PFH S 1 0 0 pM PFH S 1 0 0 pM P F O S 1 pM P F O S 1 pM PFO S 1 pM PFO S 10 pM PFO S 10 pM PFO S 10 pM PFOS 1 0 0 pM PFOS 1 0 0 pM PFOS 1 0 0 pM R osu va sta tin 0.003 pM R osu va sta tin 0.003 pM R osu va sta tin 0.003 pM R osu va sta tin 0.0 3 pM R osu va sta tin 0.0 3 pM R osu va sta tin 0.0 3 pM R o suvastatin 0.3 pM R o suvastatin 0.3 pM P FBS 1 pM P FBS 1 pM P FBS 1 pM P FB S 10 pM P FB S 10 pM PFBS 100 pM PFBS 100 pM PFH S 1 pM PFH S 1 pM PFH S 1 pM PFH S 10 pM PFH S 10 pM PFH S 1 0 0 pM PFH S 1 0 0 pM PFO S 1 pM PFO S 1 pM PFO S 1 pM PFO S 10 pM PFO S 10 pM PFOS 1 0 0 pM PFOS 1 0 0 pM R osu va sta tin 0.003 pM R osu va sta tin 0.003 pM R osu va sta tin 0.003 pM R osu va sta tin 0.0 3 pM R osu va sta tin 0.0 3 pM R o suvastatin 0.3 pM R o suvastatin 0.3 pM 14C L a b e l 3H -cholesterol (dpm ) l4C b u ty ric a cid 11671 l4C b u ty ric a cid 11805 14C b u ty r ic a c id 11641 14C b u ty r ic a c id 11648 14C b u ty r ic a c id 14C b u ty r ic a c id 11906 12251 14C b u ty r ic a c id 12599 14C b u ty r ic a c id 10509 14C b u ty r ic a c id 12593 14C b u ty r ic a c id 12245 14C b u ty r ic a c id 11423 14C b u ty r ic a c id 12013 14C b u ty r ic a c id 11885 14C b u ty r ic a c id 14C b u ty r ic a c id 11791 11061 14C b u ty r ic a c id 12385 14C b u ty r ic a c id 12579 14C b u ty r ic a c id 12107 14C b u ty r ic a c id 12774 14C b u ty r ic a c id 11196 14C b u ty r ic a c id 12355 14C b u ty r ic a c id 13007 14C b u ty r ic a c id 12240 14C p a lm itic a c id 14199 14C p a lm itic a c id 12961 14C p a lm itic a c id 13307 14C p a lm itic a c id 13107 14C p a lm itic a c id 12361 14C p a lm itic a c id 14351 14C p a lm itic a c id 12742 14C p a lm itic a c id 13653 14C p a lm itic a c id 12703 14C p a lm itic a c id 12038 14C p a lm itic a c id 13137 14C p a lm itic a c id 11960 14C p a lm itic a c id 11398 14C p a lm itic a c id 14337 14C p a lm itic a c id 11689 14C p a lm itic a c id 13496 14C p a lm itic a c id 13069 14C p a lm itic a c id 13862 14C p a lm itic a c id 14202 14C p a lm itic a c id 9771 14C p a lm itic a c id 8624 14C p a lm itic a c id 6247 14C p a lm itic a c id 8729 14C p a lm itic a c id 10667 14C p a lm itic a c id 6797 14C p a lm itic a c id 4697 14C p a lm itic a c id 9054 14C p a lm itic a c id 4674 m ix 1 input 3H cholesterol 21387 input 3H cholesterol input 3H cholesterol 20596 19529 a v e ra g e in p u t 3H c h o le s te ro l 20504 C -ch o le ste ro l (dpm ) 3180 4589 3479 4837 2793 3204 1926 2215 2141 2079 2076 2892 2655 2641 2162 137 127 162 35 33 43 30 43 978 745 963 863 429 1098 954 1536 1392 1184 1031 991 1551 1171 851 1062 1193 1377 1377 742 980 152 122 128 127 107 141 125 m ix 2 21723 17423 21082 20076 14C - c h o le s te r o l c o r r e c te d fo r recovery (dpm ) 5470 7804 6000 8337 4710 5250 3069 4231 3413 3409 3649 4833 4485 4497 3924 222 203 269 55 59 70 46 71 1383 1154 1453 1322 697 1536 1503 2259 2200 1975 1576 1663 2732 1640 1462 1580 1833 1994 1947 1525 2281 488 281 241 375 457 313 537 pg protein 3 4 8 .0 3 3 7 .9 3 4 5 .7 3 1 6 .4 344.1 3 7 9 .8 4 0 3 .5 3 8 0 .6 4 3 7 .8 4 1 2 .7 4 1 2 .6 4 6 9 .7 3 5 6 .5 3 8 5 .2 3 8 8 .3 3 8 7 .5 3 9 5 .7 3 8 7 .5 3 9 9 .5 3 9 2 .7 3 6 6 .0 3 8 2 .3 3 7 1 .9 3 3 2 .2 3 4 9 .3 3 5 0 .8 3 6 0 .9 3 5 7 .3 3 4 1 .4 3 6 8 .2 3 5 8 .7 3 8 1 .5 3 7 1 .2 3 9 8 .7 410.1 4 0 7 .0 3 5 6 .6 4 2 6 .9 4 0 7 .0 4 0 4 .8 3 9 3 .5 413.1 4 2 0 .8 3 7 4 .2 4 2 2 .3 4 7 0 .2 363.1 4 0 8 .7 4 3 7 .5 449.1 3 9 0 .9 14C - c h o le s te r o l per m g protein (dpm /m g) 15718 23097 17357 26346 13687 13825 7607 11117 7797 8259 8843 10290 12579 11673 10107 573 512 693 138 151 191 121 190 4163 3304 4142 3663 1950 4500 4082 6296 5766 5320 3952 4056 6712 4599 3424 3881 4527 5068 4712 3623 6097 1157 597 663 918 1045 696 1374 % o f control A verage % of control 1 2 6 .4 1 8 5 .7 1 3 9 .6 1 7 5 .7 2 1 1 .9 110.1 111.2 110.6 6 1 .2 8 9 .4 71.1 6 2 .7 6 6 .4 71.1 7 3 .4 8 2 .7 101.2 92.1 9 3 .9 8 1 .3 4.6 4.8 4.1 5.6 1.1 1 .3 1.2 1.5 1.0 1.2 1.5 6 0 .6 48.1 5 6 .3 6 0 .2 5 3 .3 4 0 .8 2 8 .4 6 5 .5 6 2 .4 5 9 .4 9 1 .6 8 4 .3 8 3 .9 7 7 .4 5 7 .5 5 8 .2 5 9 .0 9 7 .6 6 6 .9 8 2 .3 4 9 .8 5 7 .4 5 6 .5 6 5 .9 7 3 .7 71.1 6 8 .5 5 2 .7 8 8 .7 7 0 .7 16.8 11.7 8.7 9.7 13.4 14.3 15.2 10.1 20.0 15.1 SD 6 4 .8 0.8 15.9 8.4 10.1 0.7 0.2 0.4 7.1 17.6 4.3 7.1 1.1 2 1 .7 8.1 3.7 2 5 .5 4.4 1.3 7.0 Appendix to TNO-report of 3M-02 Final version 04-12-2006 Average [14C]-Cholesterol synthesis in rat hepatocytes (% of control) C oncentration: 1 mM 1 10 m M | 100 m M 1 0.003 m M 0.03 uM experim ent 1 2 3 4 l4C a ce ta te in co rp o ra tio n , n=4, PFBS 85.0 82 76 115 157 177 33 34.9 42.1 90 67.3 93.7 AVERAGE SD 80.8 34.4 85.3 51.7 97.2 57.3 experim ent 1 2 3 4 AVERAGE SD 14C a ce ta te in co rp o ra tio n , n=4, PFH S 91 82 84 148 136 111 63.8 91.8 38.8 154.3 35.9 100 98.7 102.8 82.7 35.4 52.5 33.1 experim ent 1 14C a ce ta te in co rp o ra tio n , n=4, PFO S 76 84 65 2 130 119 132 3 43.3 32.6 38.4 4 139.9 113.9 89 AVERAGE SD 97.3 45.7 87.4 39.6 81.1 39.7 experim ent 1 2 3 4 14C a ce ta te in co rp o ra tio n , n=4, R osuvastatin 45 40.0 6.2 3.8 11 8 1 1 AVERAGE SD 23.8 21.8 5.4 4.9 0.3 uM 3 2 0.5 0.6 1.5 1.2 C o n c e n tra tio n : 1 u M | 10 imM I 100 u M | 0 .0 0 3 uM experim ent 1 2 3 4 14C b u ty ra te in c o rp o ra tio n , n= 4, P FB S 61.0 128 92 24 146 140 175 37.9 50.7 60.3 92 52.2 118.7 AVERAGE SD 84.2 46.8 92.7 47.9 111.5 48.6 experim ent 1 2 3 4 14C b u ty ra te in c o rp o ra tio n , n= 4, PFH S 115 101 100 190 220 200 45.4 48.3 51.9 124.5 175.7 110.6 AVERAGE SD 118.7 59.2 136.3 76.5 115.6 61.8 experim ent 1 2 3 4 14C b u ty ra te in c o rp o ra tio n , n= 4, P F O S 76 98 58 262 223 286 29.1 68.8 45.5 71.1 73.4 92.1 AVERAGE SD 109.6 103.8 115.8 72.6 120.4 112.1 experim ent 1 2 3 4 14C b u ty ra te in c o rp o ra tio n , n= 4, ro s u va sta tin 24 46.0 3.7 4.8 AVERAGE SD 19.6 19.9 0.03 uM 5 5 16 1 1 5.8 7.0 0.3 uM 3.0 3 4 0.5 1.2 2.2 1.6 C oncentration: 1 uM | 10 uM | 100 uM | 0.003 uM experim ent 1 2 3 14C la u ra te in co rp o ra tio n , n= 3, P F B S 84.0 97 87 131 102 100 68.5 77.2 53.3 AVERAGE SD 94.5 32.5 92.1 13.1 80.1 24.1 1 2 3 AVERAGE SD 14C la u ra te in co rp o ra tio n , n= 3, P F H S 108 102 68 150 103 134 74.4 65.4 64.2 110.8 90.1 88.7 37.9 21.4 39.2 1 2 3 AVERAGE SD 14C la u ra te in co rp o ra tio n , n= 3, P F O S 113 85 65 119 124 125 100.4 77.6 55.6 110.8 95.5 81.9 9.5 24.9 37.6 14C la u ra te in co rp o ra tio n , n= 3, ro s u v a s ta tin 1 25 2 35.0 3 7.5 AVERAGE SD 22.5 13.9 0.03 uM 7 15 1 7.8 6.8 0.3 uM 3 3 0.5 2.2 1.4 C oncentration: 1 uM 10 uM 100 uM 0.003 uM 0.03 uM experim ent 1 3 4 14C p a lm ita te in co r poration, n=3, P FB S 76.0 56 71 50.4 54.6 37.1 56.3 40.8 62.4 AVERAGE SD 60.9 13.4 50.5 8.4 56.8 17.6 CO X LL Q_ CO II c c o o 14C p a lm ita te in co r 1 63 68 59 3 40.2 45.7 47.5 4 84.3 58.2 82.3 AVERAGE SD 62.5 22.1 57.3 11.2 62.9 17.7 14C p a lm ita te in co r poration, n=3, P F O S 1 90 62 51 3 41.6 63.1 34.5 4 57.4 71.1 70.7 AVERAGE SD 63.0 24.7 65.4 5.0 52.1 18.1 14C p a lm ita te in co r poration, n=3, ro s u v a s ta tin 1 48 20 3 11.7 7 4 11.7 14 AVERAGE SD 23.8 21.0 13.8 6.5 0.3 uM 12 5 15.1 10.7 5.2 Page A172 of A172