consumption, 22

contaminants and adulterants, 191, 195, 199, 201, 329

FDA, general, 2, 28, 30, 34

chemical components and related botanicals, 178-179, 206-207

Framework review process, 11, 100, 106-108, 110-111

historical use of supplements, 61, 137-141

history of regulation, 2, 24

litigation, 2, 31

monographs, various, 54, 55, 57, 59, 63-64, 68-69, 71-78

plant family information, 322-351

review approaches, various, 49, 51-57, 59-61, 63-64, 68-69, 71-79

monographs, 54, 55, 57, 59, 63-64, 68-69, 71-78

pregnant women, 53, 56, 60, 64, 68-69

sales value of, 19

stevia, 30, 34

supplements defined, 20

teratogenicity, plant family information, 336, 340, 348-349

C

Carcinogenicity

animal studies, 163, 164, 172, 368

chaparral, 394, 420, 432-433

chemical components and botanicals, taxonomic relatedness, 187-197

human studies, 138, 146

melatonin, 368, 370

saw palmetto, 376, 378, 451, 453, 455

shark cartilage, 381

supplements, various, 23, 75, 69, 290

Cardiovascular effects

chemical components and botanicals, taxonomic relatedness, 187-199, 381

melatonin, 369, 379

saw palmetto, 279, 377, 378, 379, 432

Cartilage, see Shark cartilage

Case reports and case series, 72

see also Adverse events;

Prototype safety monographs

adverse event reporting and, 127, 128, 135, 283

Framework review process, 88, 90, 101, 135, 283, 388-389, 422

Cell studies, 115(n.10), 158, 211, 212

see also Genetic toxicology

chaparral, 387, 399, 441-448

chromium picolinate, 373

in vitro assays, 106, 112, 151, 219-220, 223, 225, 229

Center for Food Safety and Applied Nutrition, 97, 305

Chaparral, 264-265

adverse events, 388-403, 420, 436

animal studies, 390-391, 437-439

carcinogenicity, 394, 420, 432-433

cellular studies, 387, 399, 441-448

contaminants and adulterants, 357, 358, 359, 389, 393, 398, 399

dosage and administration, 357, 387-388, 390, 391, 394-395, 396, 397-398, 420

gender factors, 396

individual components, 386-387, 401, 411-419, 449

international perspectives, 276, 396

Internet marketing, 394-395

prototype monographs, 272-275, 284-285, 287-290, 356-449

hepatoxicity, 264-265, 356-362, 387-401 (passim), 428-431, 446

immunotoxicity, 388, 394, 395

Chemical components and related botanicals, 20, 175-214, 263, 392

see also Chaparral;

Saw palmetto

age-related metabolism changes, 248

alcohol extraction, 139, 202, 203, 205, 207

alkaloids, 38, 179, 183, 186-204 (passim), 323-351 (passim)

animal studies, 187-200 (passim), 210, 211

cultivation and other conditional factors, 201-202, 205

endogenous substances, 108, 115, 175, 208-210, 214, 238, 363, 367, 372, 373

Framework review process, 11, 100, 106-108, 110-111, 377

functional relatedness, 92, 175, 208, 210-212, 279-280, 283, 299, 392, 453, 476-477

general classes and specific constituents of concern, 180-181

Front Matter (R1-R20)

Executive Summary (1-18)

1 Introduction and Background (19-42)

2 Approaches Used by Others and Existing Safety Frameworks (43-84)

3 The Framework (85-125)

4 Categories of Scientific Evidence--Human Information and Data (126-155)

5 Categories of Scientific Evidence--Animal Data (156-174)

6 Categories of Scientific Evidence--Information About Related Substances (175-216)

7 Categories of Scientific Evidence--In Vitro Data (217-234)

8 Interactions (235-246)

9 Vulnerable Groups and Prevalance of Use (247-252)

10 Scientific Principles for Integrating and Evaluating the Available Data (253-268)

11 Applying the Framework: Case Studies Using the Prototype Safety Monographs (269-291)

12 Factors Influencing Use of the Safety Framework (292-296)

13 Findings and Recommendations (297-306)

Appendix A: Existing Frameworks or Systems for Evaluating the Safety of Other Substances (307-315)

Appendix B: Scope of Work and Comments to Initial July 2002 Framework (316-321)

Appendix C: Plant Family Information (322-355)

Appendix D: Chaparral: Prototype Monograph Summary (356-362)

Appendix E: Glucosamine: Prototype Monograph Summary (363-366)

Appendix F: Melatonin: Prototype Monograph Summary (367-371)

Appendix G: Chromium Picolinate: Prototype Monograph Summary (372-375)

Appendix H: Saw Palmetto: Prototype Monograph Summary (376-379)

Appendix I: Shark Cartilage: Prototype Monograph Summary (380-384)

Appendix J: Prototype Focused Monograph: Review of Liver-Related Risks for Chaparral (385-449)

Appendix K: Protoype Focused Monograph: Review of Anti-Androgenic Risks of Saw Palmetto Ingestion by Women (450-477)

Appendix L: Acknowledgements (478-480)

Appendix M: Biographical Sketches of Commitee Members (481-488)

Index (489-506)