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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction (2001)
Institute of Medicine (IOM)

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607
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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction

Index

A

Abortion,

see Spontaneous abortions

Accidents

automobile, 42–44 (passim), 46, 50, 56

fires, vii, 570–571

Accord, 4, 65, 95, 603

Acetylcholine (Ach), 161, 244–245, 252, 254, 266, 269, 347, 568

Action on Smoking and Health, 126

Activated charcoal filters,

see Charcoal filters

Added ingredients,

see Additives

Addiction, vii, 1, 5, 25, 28, 29, 35, 40, 41, 161, 162, 201, 601

see also Alcohol and drug abuse;

Relapse

adolescents, 261

advertising and, 66

African Americans, 407

dose-response relationship, 255–256, 264, 266

FDA attempt to regulate tobacco, 126, 127, 129, 258, 604

genetic predisposition to, 161, 256, 347–348

nicotine pharmacology, 161, 243, 244, 245, 248, 254–260 (passim), 263–267 (passim)

psychological and behavioral aspects, 41, 118, 161, 254, 256–257, 259

risk perception, 68

Surgeon General’s report, 24, 600

withdrawal, 405, 569

drug treatments, 96, 101, 104–114 (passim), 123

nicotine pharmacology, 161, 244, 245, 248, 254–260 (passim), 263–267 (passim)

Additives, 82, 86, 90–91, 432, 571, 598, 601

advertising, 72, 73–74

animal models, 90–91, 149

blending processes, viii, 26, 82, 85, 87, 94, 128, 209, 287

FDA regulation, 128, 224

menthol, 62, 64, 72, 73, 77, 86–87, 98, 183, 319, 406–407, 438, 439

PREP risk assessment, 144, 149, 165, 212

regulation, 128, 149, 209, 210, 212, 224–225

risk perception, 72–74, 77

smokeless tobacco, 299–300

surveillance, 189, 196

Adolescents, 67, 235, 320–321, 602

see also Schools

addiction, 261

drug treatments, 112, 116

 Page
607

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction Index A Abortion, see Spontaneous abortions Accidents automobile, 42–44 (passim), 46, 50, 56 fires, vii, 570–571 Accord, 4, 65, 95, 603 Acetylcholine (Ach), 161, 244–245, 252, 254, 266, 269, 347, 568 Action on Smoking and Health, 126 Activated charcoal filters, see Charcoal filters Added ingredients, see Additives Addiction, vii, 1, 5, 25, 28, 29, 35, 40, 41, 161, 162, 201, 601 see also Alcohol and drug abuse; Relapse adolescents, 261 advertising and, 66 African Americans, 407 dose-response relationship, 255–256, 264, 266 FDA attempt to regulate tobacco, 126, 127, 129, 258, 604 genetic predisposition to, 161, 256, 347–348 nicotine pharmacology, 161, 243, 244, 245, 248, 254–260 (passim), 263–267 (passim) psychological and behavioral aspects, 41, 118, 161, 254, 256–257, 259 risk perception, 68 Surgeon General’s report, 24, 600 withdrawal, 405, 569 drug treatments, 96, 101, 104–114 (passim), 123 nicotine pharmacology, 161, 244, 245, 248, 254–260 (passim), 263–267 (passim) Additives, 82, 86, 90–91, 432, 571, 598, 601 advertising, 72, 73–74 animal models, 90–91, 149 blending processes, viii, 26, 82, 85, 87, 94, 128, 209, 287 FDA regulation, 128, 224 menthol, 62, 64, 72, 73, 77, 86–87, 98, 183, 319, 406–407, 438, 439 PREP risk assessment, 144, 149, 165, 212 regulation, 128, 149, 209, 210, 212, 224–225 risk perception, 72–74, 77 smokeless tobacco, 299–300 surveillance, 189, 196 Adolescents, 67, 235, 320–321, 602 see also Schools addiction, 261 drug treatments, 112, 116

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction gender factors, 74, 172, 543, 545, 552 sexual behavior, 44–46, 50, 51 National Youth Tobacco Survey, 185–187 pregnancy, 44, 172, 543, 545, 552 prevalence of tobacco use, 1, 22, 38, 319 risk perception, 41, 68, 72, 73–74, 112, 185 sexual behavior, 44–46, 50, 51; see also “pregnancy” supra smokeless tobacco, 302 state laws banning sales to, 120, 125, 202, 604 Surgeon General’s reports, 24, 125, 598, 601 surveillance, 185, 192 Youth Risk Behavior Survey, 93, 185–187, 261, 320–321 Adrenal hormones, 105, 107, 108, 109, 110, 244, 245, 252, 253, 480, 549 Adult Use of Tobacco Surveys (AUTS), 69, 76 Advance, 4, 92 Advertising, 7, 8, 26, 32, 72, 86 see also Labeling; Marketing additives, 72, 73–74 antismoking, 125 bans on, 120, 125, 597, 602 children and adolescents, 24 cigarette-like products, 94 historical perspectives, 60–66, 72–73, 74, 76, 120, 125–126, 595, 597, 602, 603 regulation of, 7, 10, 120, 125–126, 127, 128, 141, 203, 206, 207, 208, 211, 216–221, 222, 229, 232, 595, 597, 602, 603 smokeless tobacco, 93 Aerosols, viii, 284–285 cigarette-like products, 93–94 nicotine inhalers, 97–98 African Americans, 321, 603 birthweight, 548 cancer, 406–407, 416 mentholated cigarettes, 72, 73, 86, 406–407 nicotine metabolism, 250 Age factors see also Adolescents; Birthweight; Children; Reproductive and developmental effects addiction, 261 body weight, 569 cancer, 389, 390, 405, 410–413, 420, 421, 424, 425 cardiovascular disease, 472, 473, 474–475, 482 chronic obstructive pulmonary (COPD), 503, 508, 509–511, 513, 515 dementia, 564 dose-response relationship, 164 environmental tobacco smoke (ETS), 424, 509–511 influenza and pneumonia, 526 initiation of smoking, 73–74, 185, 191, 319, 331, 381, 395, 405, 425, 508, 543, 601 nicotine metabolism, 250 ocular disease, 566 orthopedic disease, 565 PREPs, 76, 161, 164, 319, 321, 331 reproductive and developmental effects, 547 teenage pregnancy, 44, 172, 543, 545, 552 risk assessment, general, 67, 145, 186, 321 smokeless tobacco use, 93, 302 surveillance, 185, 186, 191, 192, 194, 321 Agency for Healthcare Research and Quality, 172 AIDS, 23, 44, 45, 48, 52, 53 Air pollutants, 44, 54, 225, 296, 333, 390, 505, 508–509, 519 occupational toxins, 33, 140, 151, 164, 166, 180, 195, 298, 329, 332, 350, 375, 377, 390, 408, 419, 420, 431, 433, 508, 599 Alcohol and drug abuse auto accidents, 42, 43, 44, 46, 50, 56 behavioral treatments, 118–119 dementia, 564 measures of, 255, 257–266 (passim) methadone, 42, 48, 49–50, 51, 52, 55, 114 naltrexone, 108 National Household Survey on Drug Abuse, 50, 92–93, 185–187, 260, 261 oropharyngeal disease, 415–416, 418 pharmacodynamics, 253, 570 policy, 39–40, 46–50, 51, 52, 53, 55, 56, 601

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction pregnant women, 172, 545, 547 psychological mechanisms, 41 relapse, 47, 49 surveillance, 195 synergistic effects, 342, 415–416, 418, 426, 428 Alzheimer’s disease, 254, 564–565 American Cancer Society Cancer Prevention Study (CPS) I/II, 67, 75, 76, 167, 170, 400, 487, 512–513, 530, 531 American Indians, 22, 543, 603 American Legacy Foundation Survey, 320–321 Aneurysms, 470, 481, 491 Animal models, 12–13, 15, 17, 34, 141, 149, 175, 287, 291, 293 addiction, 258, 263–264, 265–266 additives, 90–91, 149 cardiovascular disease, 149, 479, 486 cancer, 13, 293–295, 367, 374, 376, 383, 384–387, 422, 429, 432–433, 434, 435 cost of, 383 DNA adducts, 327, 385–387 dose-response relationship, 16, 145, 163, 165 fetal lung development, 511 infectious diseases, 296–297 nicotine antibodies, 107–108 nicotine pharmacology, 244, 253, 258, 268 PREP risk assessment, 144, 145, 147, 148–149, 162, 163, 165, 208, 212–213, 303, 350, 351, 384–386 regulatory principles, 10, 208, 212–213, 215 reproductive and developmental effects, 550 transgenic animals, 298–299, 385, 391 Antagonists, 4, 106–108, 110, 116, 244 mecamylamine, 107, 124, 266 Antibodies, 107–108, 297, 330–331 lymphocytes, 156, 296–297, 314, 338, 346, 376, 399, 417, 436, 518, 519 Antidepressants, 4, 104–106 see also Bupropion; Zyban nortriptyline, 4, 104, 106, 124 Aromatic amines, 148, 374, 377–378, 379, 420–421 Arsenic, 72, 148, 184, 374 Arthritis, see Rheumatoid arthritis Asbestos, 89, 298, 408, 501, 599 Asians/Pacific Islanders, 22, 250, 406, 407, 543, 603 Japanese, 88–89, 261, 286, 342, 409 Asthma, 170, 500–501, 518–525, 527, 530–531, 551 Atherosclerosis, 157, 162, 169, 253, 270, 296, 313, 332, 339, 343, 471, 472, 476–477, 479–483 (passim), 485, 490, 492, 493 Attitudes and beliefs, 54 see also Depression; Risk perception desire to cease smoking, 22, 71, 74–76, 78, 122, 186, 476, 512, 514, 515 negative opinion of tobacco use, 124–125, 187, 319 pregnant women, 187–188 public understanding of PREP content, 60 surveillance of, 8, 10, 185–188 (passim), 192, 196, 197 toward unsafe behavior, negative attitudes, 43 Automobile safety, vii regulation, 41–44, 50, 52, 53, 56 AUTS, see Adult Use of Tobacco Surveys B Behavioral effects of tobacco use, 3, 118, 389 see also Inhalation depth and intensity; Smoking topography addiction, 41, 118, 161, 254, 256–257, 259 childhood cognitive/behavioral disorders, 268, 550 cigarettes smoked per day, 22, 74, 88–89, 102, 113, 115, 119, 120, 151, 163, 164, 167, 170, 173, 300, 319, 343, 349, 375, 391, 392, 395, 396, 398–399, 401, 404, 412, 419, 437, 474, 487, 488, 489, 512, 513–514, 515, 516, 530 compensatory smoking, 2, 26, 67, 88, 121, 164, 219, 266, 285, 322, 380, 402, 403, 405, 477, 517 desire to cease smoking, 22, 71, 74–76, 78, 186, 476, 512, 514, 515 PREPs, 7, 73–76, 185, 197, 315 surveillance, 183, 185–188, 191–192, 195, 197

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction Behavioral Risk Factor Surveillance System, 185–187, 320–321, 543 Behavioral treatments, 116–119, 121, 532 drug treatment, general, and, 118–119 nicotine replacement products and, 96, 115 Beliefs, see Attitudes and beliefs Benzene, 89, 95, 148, 287, 290, 374, 379 Benzo[a]pyrene (BaP), 86, 87, 94, 148, 319, 373–374, 375–376, 380, 391–392, 407, 544 Bidis, 82, 83, 321 Biologically effective dose, 150, 160, 309–315 (passim), 326–333, 348, 350, 351, 353 cancer, 151, 166, 313, 327–330, 332–333, 380, 381, 388, 433, 435, 437 defined, 150, 311, 388 Biomarkers, 11–12, 13, 16, 121, 142, 144, 145, 149–150, 162–163, 240, 309–317, 323–366 see also Cotinine; In vitro assays; Plasma markers; Serum markers; Surrogate markers; Urine biomarkers biologically effective dose, 150, 151, 160, 166, 309–315 (passim), 326–333, 348, 350, 351, 353, 380, 381, 388, 433, 435, 437 biopsies, 311, 323, 341, 414, 417, 437, 518 bronchoalveolar lavage, 13, 156, 295, 338–339, 343–344, 437, 517 carbon monoxide as, 313, 323, 324–325, 330–331 carcinogenesis, general, 150–151, 153, 154, 163–167 (passim), 333, 380, 381, 388, 422, 424, 433, 435–436, 437 see also “mutagenesis” infra cotinine, 407, 422, 424, 429 DNA adducts, 153, 292, 293, 313, 314, 327–335 (passim), 341, 346, 348, 353, 368–370 (passim), 375–378 (passim), 385–390 (passim), 399, 405, 409, 417, 420–424 (passim), 429, 435, 492 serum, 333, 422 surrogate markers, 166, 327, 330, 435–436 urine, 326, 353–354, 376, 378, 407, 420–421, 422, 424, 429, 435, 437 cardiovascular disease, 12, 154, 156, 168, 169, 253, 313, 332, 336–337, 339, 343, 354, 483–486, 490–491 surrogate markers, 168, 483–486, 490 chronic obstructive pulmonary disease (COPD), 170, 502 cohort studies, 352–353, 354, 438 cost of techniques, 153, 315, 318, 322 definitional issues, 150, 311 environmental tobacco smoke (ETS), 317, 323, 329, 348, 422, 436, 491 enzymatic processes, 314, 327, 334, 342, 345–346, 389 epidemiology and, 142, 160, 161, 309, 339, 438 exposure, 145, 150–161, 237, 309–317, 323–355, 396–397 internal exposure, 150, 151, 160, 163–164, 309, 323, 349, 350, 351, 388, 396, 431, 435, 437 half-life, 152, 154, 156, 157, 158, 250, 297, 316, 323, 324, 328, 333, 376, 422 internal exposure, 150, 151, 160, 163–164, 309, 323, 349, 350, 351–352, 388, 396, 431, 435, 437 lipids, 12, 154, 169, 243, 253, 314, 330–331, 336–337, 343, 378–379, 471, 479, 482, 485, 486, 491–492 leukotrines, 156, 344, 388, 519–520, 563 mutagenesis, 313, 314, 323, 326, 327, 334, 340–342, 345, 346–347, 353; see also “carcinogenesis” supra nicotine, 323, 324–325, 326, 347 see also Cotinine plasma markers, 99, 113, 250, 293 nonneoplastic respiratory disease, 170–171, 501–503, 506, 507, 512, 517, 527, 531, 532 urine, 503, 506, 523, 524, 525, 529, 531 oropharyngeal disease, 156, 333, 342, 338–339 platelet activation, 12, 156, 157, 168, 169, 252, 253, 296, 337–339, 343, 354, 479, 480, 481, 483–486, 490, 491, 492, 493, 561 PREP risk assessment, 142, 144, 145, 150–161, 162–163, 165, 237, 309–317, 323–352, 388, 435–436, 553

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction regulatory issues, 10, 11–12, 207–208, 211, 220, 348–349 reproductive and developmental effects, 174, 191, 545, 548, 553, 570, 572 research recommendations, 352–355, 438, 491 saliva, 209, 267, 300, 311, 323, 325, 422, 428, 523, 525 standards, 348–349 surveillance, 182, 184–185, 190–191, 196 vascular activation, 12, 157, 169, 337, 490–491 Biopsies, 311, 323, 341, 414, 417, 437, 518 Birthweight, 11, 23, 24, 149, 172, 173–174, 188, 193, 212, 267, 340–341, 344, 529, 543, 547–549, 550, 551, 552, 554, 596 Black persons, see African Americans Black vs blond tobacco bladder cancer, 419 hemoglobin adducts, 332 lung cancer, 401–402 oropharnygeal cancer, 416 Bladder cancer, 24, 333, 355, 368, 377–378, 380, 388, 390, 418–421, 428 Blending processes, viii, 26, 82, 85, 87, 94, 128, 209, 287 see also Black vs blond tobacco Blond tobacco, see Black vs blond tobacco Blood pressure, 154, 336–337, 343, 479, 482, 491 hypertension, 252, 319, 477, 479, 481, 547, 548, 568 antihypertensive drugs, 4, 107, 108–109, 124 preeclampsia, 268, 560, 572 low, 107, 109, 252, 268, 269 Body weight, 340–341, 343, 344, 422, 482, 565, 569–570 age factors, 569 birthweight, 11, 23, 24, 149, 172, 173–174, 188, 193, 212, 267, 340–341, 344, 529, 543, 547–549, 550, 551, 552, 554, 596 nicotine effects, 126, 158–159, 162, 255, 267, 270, 568–569 ventilation and, 286 Bone, see Orthopedic effects Bradford Hill criteria, 381, 382 Breast cancer, 385, 395, 598 British American Tobacco Company, 65 Bronchi, 24, 156, 500, 505, 514, 520, 522, 526, 551 bronchitis, 21, 295, 338, 502, 503, 505, 510, 525, 529, 551 cancer and carcinogenesis, 285, 298, 375, 376, 391, 392, 393, 437, 518 epithelium, 298, 375, 376, 393 Bronchoalveolar lavage, 13, 156, 295, 338–339, 343–344, 437, 517 Bronchoscopy, 157, 171, 339, 392, 502–503, 517, 531 Brown & Williamson, 21, 61, 92, 184, 204, 228, 584, 601 Bupropion, 4, 98, 104, 105–106, 115, 231, 233–234, 347 see also Zyban FDA actions, 123–124, 172, 552–553 pregnant women, 172, 174, 552–553, 554 Zyban, 30, 104, 123–124 Buspirone, 109 C Canada, 219 Cancer and carcinogens, 1, 4, 23, 147–148, 163–167, 174, 367–469 additives, 90–91 adenocarcinomas (AD), 392, 393, 404 African Americans, 406–407, 416 age factors, 389, 390, 405, 410–413, 420, 421, 424, 425 animal models, 13, 293–295, 367, 374, 376, 383, 384–387, 422, 429, 432–433, 434, 435 aromatic amines, 148, 374, 377–378, 379, 420–421 benzene, 89, 95, 148, 287, 290, 374, 379 benzo[a]pyrene (BaP), 86, 87, 94, 148, 319, 373–374, 375–376, 380, 391–392, 407, 544 biologically effective dose, 151, 166, 313, 327–330, 332–333, 380, 381, 388, 433, 435, 437 biomarkers, 150–151, 153, 154, 163–167 (passim), 333, 380, 381, 388, 422, 424, 433, 435–436, 437

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction adducts, 153, 292, 293, 313, 314, 327–335 (passim), 341, 346, 348, 353, 368–370 (passim), 375–378 (passim), 386–390 (passim), 399, 405, 409, 417, 420–424 (passim), 429, 435, 492 cotinine, 407, 422, 424, 429 serum, 333, 422 surrogate markers, 166, 327, 330, 435–436 urine, 326, 353–354, 376, 378, 407, 420–421, 422, 424, 429, 435, 437 biopsies, 311, 323, 341, 414, 417, 437, 518 bladder, 24, 333, 355, 368, 377–378, 380, 388, 390, 418–421, 428 breast, 385, 395, 598 bronchial, 285, 298, 375, 376, 391, 392, 393, 437, 518 carbon monoxide, 294, 407 cervical, 24 clinical research, 165, 383, 414, 433, 437 cohort studies, 377, 395, 396–397, 400–403, 405, 411–413, 420 colonic, 394 definition of carcinogen, 368 dietary factors, 164, 166, 375, 376, 390, 404, 406, 408, 409, 414, 431, 433 dose-response relationship, 163–165, 167, 334–340, 381, 395–397, 415, 416, 419, 421, 431; see also “biologically effective dose” supra endometrial, 368, 421–422 environmental tobacco smoke, 53, 390, 396, 398, 408, 422–424, 434, 439, 604 enzymatic processes, 368, 369, 370, 376, 377, 389, 394, 433, 436 epidemiology, 165, 166, 367, 383, 418, 420, 424 epithelial cells, 375, 376, 393, 394, 416, 420–421 esophagus, 1, 23, 24, 232, 372, 377, 425, 429, 597 exposure, 383–384, 390, 395–397, 398–399, 401, 404, 412, 419, 420, 437; see also “dose-response relationship” supra filtered cigarettes, 91, 164, 332, 399–400, 402–404, 405, 416, 419–420, 431 gender factors, 389, 416, 418, 419, 421, 424, 426, 436 breast, 385, 395, 598 endometrial, 368, 421–422 lung, 24, 401, 402–403, 404–406, 410, 411, 412, 413, 598, 599 head and neck, 195, 301, 372, 427, 428 historical perspectives, 21–26 (passim), 367, 594, 595, 597, 598, 600, 604; see also Surgeon General incidence, 367, 384, 392, 410, 411, 415, 418 inflammation, 394, 416 inhalation depth and retention, 390, 392, 395, 420, 426 international perspectives, 88–89, 407–408, 418, 423, 424, 425 in vitro assays, 154, 165, 367, 376, 383–384, 385, 391–392, 432 large-cell carcinomas, 392, 393 liver, 376, 377, 378, 385, 386, 420, 430 low-yield products, general, 399–404 lung, viii, 21, 23, 24, 66, 67, 86, 88–89, 149, 166–167, 192, 193, 215, 293–295, 296–297, 302, 333, 342, 355, 368, 372, 385, 386, 388, 390, 391–415, 423, 425, 426, 431, 598 cohort studies, 395, 396–397, 400–403, 405, 411–413 mortality, 392, 398, 411–414 metastasis, 297, 395, 418, 501 mortality, 392, 398, 400, 411–414, 415, 418, 419, 426, 434 nicotine as carcinogen, 167, 402, 403, 405 nitrosamines, 4, 67, 86, 87, 91–92, 93, 148, 151, 210, 215, 294, 300, 301, 319, 326–327, 328, 348, 373–374, 376–377, 379, 380, 403, 405, 429–430, 603, 604 environmental tobacco smoke, 424 racial/ethnic differences, 406, 407 smokeless tobacco, 4, 93, 428, 429 oncogenes, 294, 341–342, 371, 389, 391, 393 oropharyngeal, 23, 167, 301, 333, 342, 368, 372, 415–418, 425, 427–429, 597 pancreatic, 372 particulates, 148, 374, 436 polycyclic aromatic hydrocarbons (PAHs), 86, 148, 149, 295, 322, 326–327, 328–331, 333, 348, 374, 375–376, 377, 379, 391–392, 418, 570

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction PREP risk assessment, 3, 150–151, 153, 154, 163–167, 208, 218, 222, 373, 374–375, 379–392, 421, 430–439 in vitro assays, 154, 167, 367, 383–384, 385 low-yield products, general, 399–404 lung cancer, 294–295, 395–399, 407–409 see also “biomarkers” supra processing of tobacco, 85 race/ethnicity, 406–408, 416, 436 regulatory issues, 10, 208, 215 research methodology, 378, 379–394, 410, 434–439 research recommendations, 434–439 serum markers, 333, 422 small-cell lung carcinomas (SCLC), 392, 393–394, 395, 402, 404 smokeless tobacco, 4, 93, 300–301, 426–429 socioeconomic factors, 407, 414; see also “race/ethnicity” supra squamous cell carcinomas (SCC), 67, 299, 301, 372, 392, 393, 404, 415, 418 surrogate markers, 166, 327, 330, 435–436 tar, 373–374, 399–404, 407 tumor suppressor genes (including p53), 155, 336, 341–342, 343, 371–372, 375, 376, 391–392, 393–394, 405, 409, 415, 417, 418–419, 420, 421, 428–429, 435 urine biomarkers, 326, 353–354, 376, 378, 407, 420–421, 422, 424, 429, 435, 437 volatile organic compounds, 89, 148, 374 Cancer Prevention Study (CPS) I/II, 67, 75, 76, 167, 170, 400, 487, 512–513, 530, 531 Carbon monoxide, 2, 24, 26, 86, 288, 517, 570, 597 see also Potential reduced-exposure products (PREPs) behavioral treatments and reduction of, 117 as biomarker, 313, 323, 324–325, 330–331 cancer, 294, 407 cardiovascular disease, 168, 481, 487 cigarette-like products, 94, 95 drug treatments and reduction of, 110, 113, 114 regulatory issues, 210, 218 reproductive and developmental effects, 172, 173–174, 549, 550, 552, 554 smoker knowledge of, 72–73 surveillance, 184 yield assessments, 87, 88, 90, 92, 94, 95, 184, 210 Carcinogens, see Cancer and carcinogens Cardiovascular disease, 4, 24, 252–253, 302, 470–499 see also Blood pressure; Extracardiac vascular disease age factors, 472, 473, 474–475, 482 aneurysms, 470, 481, 491 animal models, 149, 479, 486 atherosclerosis, 157, 162, 169, 253, 270, 296, 313, 332, 339, 343, 471, 472, 476–477, 479–483 (passim), 485, 490, 492, 493 biomarkers, 12, 154, 156, 168, 313, 332, 336–337, 339, 343, 354 cholesterol levels, 289, 296, 477, 482 cotinine, 168, 487 platelet activation, 12, 156, 157, 168, 169, 252, 253, 296, 337–339, 343, 354, 479, 480, 481, 483–486, 490–491, 492, 493, 561 surrogate markers, 168, 483–486, 490 urine, 485, 486 carbon monoxide, 168, 481, 487 children, 482, 493 cholesterol levels, 289, 296, 477, 482 clinical research, 168, 169–170, 212, 491 coronary heart disease, viii, 1, 21, 23, 67, 157, 195, 208, 212, 222, 252–253, 347, 470, 471–481, 483, 487, 488, 505, 599 cotinine, 168, 487 dose-response relationship, 167–168, 169, 471, 472, 473, 477, 483, 486–487 endothelial function, 479, 480, 481, 484–485, 486, 490, 491, 492 environmental tobacco smoke (ETS), 169, 470, 478, 491 enzymatic processes, 478, 484, 487 epidemiology, 471, 472, 473, 477

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction exposure, 474, 477; see also “dose-response relationship” supra filtered cigarettes, 168 gender factors, 168, 472, 473, 477, 481, 482 genetic factors, 478, 490, 492 incidence, 167, 470, 471, 472, 473, 479, 487 inflammation, 168, 252, 253, 270, 291, 482–483, 485, 490, 491, 492 in vitro assays, 168, 480 lipids and lipoproteins, 12, 154, 169, 253, 314, 330, 336–337, 343, 471, 479, 482, 485, 486, 491–492 low-yield products, 471, 477 mortality, 470, 472, 473, 477, 487 nicotine, 168, 470–471 nicotine replacement therapy (NRT), 98–99, 112, 115, 252–253, 471 platelet activation, 12, 156, 157, 168, 169, 252, 253, 296, 337–339, 343, 354, 479, 480, 481, 483–486, 490–491, 492, 493, 561 pregnant smokers, children of, 545, 548, 552 regulatory issues, 10, 208, 212 research recommendations, 491–493 risk assessment, 149, 154, 162, 167–170, 174, 208, 212, 222, 470–499, 598, 599 risk perception, 68 stroke, 24, 168, 470, 473, 476, 487, 489, 600 surgery, 473, 476 surrogate markers, 168, 483–486, 490 surveillance, 188, 193, 195 synergistic effects of toxins, 477–478 thrombosis, 154, 157, 336–337, 339, 356, 481, 485–486, 491 urine biomarkers, 485, 486 vascular activation, 12, 157, 169, 337, 490–491, 493 Caucasians, 73, 86, 250, 406, 407, 416, 513, 543, 548 Cell cultures, see In vitro assay Centers for Disease Control and Prevention (CDC), 207, 221 smokeless tobacco, 93 surveillance, general, 180, 184, 185 Youth Risk Behavior Survey, 93, 185–187, 261, 320–321 Cerebrovascular disease, see Stroke Cessation programs, vii, x, 24, 41, 116–119, 352 see also Behavioral treatments; Chewing gum; Drug treatments Oral/nasal sprays; Patches; Psychotrophic drugs; School-based prevention/cessation programs Charcoal filters, 88, 89, 92, 94, 286, 287, 406, 603 Chewing gum, vii, 4, 5, 14, 91, 96, 98, 99, 101, 103, 113–114, 115, 129, 253, 266–267, 599 cardiovascular disease, 471 Nicorete, 97, 123, 129 Chewing tobacco, 83, 84, 247–248, 426, 428 Children, 320–321 see also Adolescents; Birthweight; Reproductive and developmental disorders; Schools advertising, 24 asthma, 501, 518–525 (passim), 530, 551 cardiovascular disease, 482, 493 cognitive deficits, 268, 550–551 environmental tobacco smoke, 286, 348, 422, 500, 510–511, 521, 522–525, 528–530, 549; see also Family/home factors nonneoplastic respiratory diseases, 500, 501, 506, 508, 510–511, 518–526 (passim), 528–530, 551 prevalence of tobacco use, 1 respiratory infections, 501, 506, 526, 528–529, 551 sales of tobacco to, 120, 125, 202, 604 Cholesterol levels, 289, 296, 477, 482 Chromosomes, 152, 293, 313, 314, 333, 334–335, 340, 341, 342, 346, 368, 369, 372, 389, 391, 393, 406, 414–415, 417, 419, 420, 435, 545 see also Mutagenesis and mutagens loss of heterozygosity, 152, 313, 314, 334, 340, 342, 391, 393, 414–415, 419, 435 Chronic obstructive pulmonary disease (COPD), 1, 21, 23, 149, 174, 302, 500, 503–518, 520, 527, 530–531, 532, 584, 598, 599 age factors, 503, 508, 509–511, 513, 515 animal studies, 13, 295 biomarkers, 170, 502

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction bronchitis, 21, 295, 338, 502, 503, 505, 510, 525, 529, 551 clinical studies, 13, 171 definition of, 503 epidemiology, 503–505, 509, 512 gender factors, 500, 509, 512, 514, 515, 516 mortality, 505, 508, 509, 512, 513–514 Surgeon General’s report, 24 synergistic effects of toxins, 508–509 time factors, 503, 511–512 ventilation, 503, 510 Cigarette Labeling and Advertising Act, 125 Cigars, viii, 82, 83, 85, 243–244, 425–426, 473, 508, 597 Clinical research, 7, 13, 16, 17, 34, 115–116, 147, 175–176, 232, 238, 352, 584 see also Biomarkers addiction, 263, 264–266 behavioral treatments, 116–118 body weight, 570 cancer, 165, 383, 414, 433, 437 cardiovascular disease, 168, 169–170, 212, 491 clonidine, 108–109 cytochrome P-450, 109–110 depression, 569 antidepressants, 105–106, 115–116 FDA drug approval criteria, 122, 215, 227 nicotine antagonists, 107 nicotine replacement products, 96, 101–103, 113–115, 533 nonneoplastic respiratory disease, 13, 171, 511–512, 514, 518, 522, 523–525, 529, 530, 532–533 regulatory issues, 122, 208, 209, 212, 213, 215, 227, 229 reproductive and developmental effects, 173–174, 547, 548, 554 subjects unwilling/unable to quit, 122 surveillance and, 183, 193, 197 tobacco industry product testing, 128 Clonidine, 4, 108–109, 124 Coalition on Smoking and Health, 126 Cognitive effects aging, 162 dementia, 174, 254, 564–565 developmental disorders, 268, 550–551 memory, 254, 319, 564 nicotine, 254, 255, 259, 270, 564 Cohort studies, 174, 193, 196, 437–438, 482, 548, 567 biomarkers, 352–353, 354, 438 bladder cancer, 377, 420 chronic obstructive pulmonary disease (COPD), 511 diabetes, 567 lung cancer, 395, 396–397, 400–403, 405, 411–413 pregnant women, 173, 547 College of American Pathologists, 349 Colon cancer, 394 inflammatory bowel disease, 174, 302, 560, 561–562, 574 Combustion, viii, 3, 4, 66, 210, 598 cigarette-like products, 93 fires and fire-safe cigarettes, 87, 571, 604 measurement, 284 nicotine pharmacology, 243 surveillance, 184 temperature factors, viii, 27, 210, 284 Compensatory smoking, 2, 26, 67, 88, 121, 164, 219, 266, 285, 322, 380, 402, 403, 405, 477, 517 Comprehensive Smokeless Tobacco Health Education Act, 125 Comprehensive Smoking Health Education Act, 125 Consumer Product Safety Act, 125 Contraceptives devices, 45 oral, 477, 481, 544, 597 Controlled Substances Act, 123, 125 COPD, see Chronic obstructive pulmonary disease Coronary heart disease, viii, 1, 21, 23, 67, 157, 195, 208, 212, 222, 252–253, 347, 470, 471–481, 483, 487, 488, 505, 599 Coronary vascular disease, see Cardiovascular disease Cost factors, monetary, 383 aggregating harm, 55 animal models, 383 auto accidents, 44 biomarkers, 153, 315, 318, 322 cigarettes, 119, 129, 187, 262 taxation, 119, 128, 202, 596, 603 drug treatments, 110 funding, 49, 215, 218, 229

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction health insurance discounts, 598 in vitro studies, 149 nicotine replacement products, 101–102, 129, 554–555 surveillance, 181, 195 Cotinine, 174, 184–185, 187, 293, 321, 323, 324, 325, 326, 348, 353 carcinogenesis, 407, 422, 424, 429 cardiovascular disease, 168, 487 drug treatments, 109–110, 114 nonneoplastic respiratory disease, 517, 523, 525, 526, 529, 530, 532 pharmacology of, 248, 249, 250, 265 pregnancy, 545, 548, 553, 572 surveillance, 184–185, 187 Court cases, see Litigation Crohn’s disease, 561–562, 574 Curing of tobacco, 8, 82, 83, 84, 91, 128, 189, 209, 299–300 Current Population Survey, 185–187 Cyanide, 72, 89, 291, 324–325, 401, 549, 561, 572 Cytochrome P-450, 109, 152, 248, 269, 298, 323, 327, 334, 342, 375, 377, 378, 385, 409, 417, 421, 570 D Definitional issues, 27–28 see also Standards biomarkers assessment, 150, 311 carcinogen, 368 chronic obstructive pulmonary (COPD), 503 cigar, 83 cigarette, 27, 82, 83 Diagnostic and Statistical Manual of Mental Disorders (DSM), 255, 257, 258–259, 260–262 exposure, 1, 27–28, 311 harm reduction, 2, 25, 38–40 hazard identification, 33–34 mutagen, 368 nicotine, 27, 126 PREPs, 3, 28, 205 regulatory, 11, 27–28, 30, 124, 126, 205, 225–226 safer cigarette, 2, 25 surveillance, 180, 181, 194 tobacco constituent, 368 Dementia, 174 Alzheimer’s disease, 254, 564–565 Demographic factors, see Age factors; Educational attainment; Genderfactors; Military personnel; Race/ethnicity; Socioeconomic status Department of Justice, 603 Depression, 104, 174, 186, 256–257, 347, 568–569 antidepressants, 105–106, 115–116, 254, 256, 570 Dermatologic diseases, 158, 174, 193–194, 246, 301, 338–339, 385, 566 Developmental disorders, see Reproductive and developmental disorders Devices, see Medical devices Diabetes, 174, 482, 548, 567 Diagnostic and Statistical Manual of Mental Disorders (DSM), 255, 257, 258–259, 260–262 Dietary factors, 89, 151, 175, 206, 294, 296, 325, 329, 333, 508, 573 cancer, 164, 166, 375, 376, 390, 404, 406, 408, 409, 414, 431, 433 pregnancy, 547 DNA, 291–292, 294, 299, 313, 314–315, 342–343, 344–347, 353, 368–370, 372, 384, 385, 486, 492 adducts, 153, 292, 293, 313, 327–335 (passim), 341, 346, 348, 353, 368–370 (passim), 372, 375–378 (passim), 385–390 (passim), 398–399, 405, 409, 417, 420–424 (passim), 429, 435, 492 chromosomes, 152, 293, 313, 314, 333, 334–335, 340, 341, 342, 346, 368, 369, 372, 389, 391, 393, 406, 414–415, 417, 419, 420, 435, 545 loss of heterozygosity, 152, 313, 314, 334, 340, 342, 391, 393, 414–415, 419, 435 repair, 152, 315, 326, 332, 334, 342–347 (passim), 369–370, 372, 376, 377, 378, 388, 389, 390, 394, 399, 409 478 Dopamine, 105, 109, 110, 244, 245, 256, 257, 266, 347–348, 551, 568, 571, 572 Dose-response relationship, viii, ix, 9, 11, 14, 15, 16, 33, 34, 316, 326–333, 343

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction see also Biologically effective dose; Exposure addiction, 255–256, 264, 266 age factors, 164 alcohol use, 415, 416 animal models, 16, 145, 163, 165 antidepressants, 105–106 cancer, 163–165, 167, 334–340, 381, 395–397, 415, 416, 419, 421, 431 cardiovascular disease, 167–168, 169, 471, 472, 473, 477, 483, 486–487 dermatologic conditions, 566 environmental tobacco smoke (ETS), 423–424, 436 exposure-to-adverse effect, ix, 140, 145, 166, 511, 530 gender factors, 164 historical perspectives, 23 nicotine replacement doses per day, 255–256, 264, 266 nonneoplastic respiratory disease, 170, 171, 510–514, 521, 523, 527–528, 531, 532 ocular disease, 565 oropharyngeal disease, 415 Parkinson’s disease, 571–572 PREP risk assessment, 14, 15, 33, 34, 140, 141, 144–147, 152, 154, 156, 158, 159, 160, 167, 237–238, 271, 310, 312, 325, 326, 352, 381, 395–396 race/ethnicity, 164, 407 renal disease, 567–568 rheumatoid arthritis, 562 reproductive and developmental effects, 172–173, 544, 545, 546, 548, 550, 554–555 time factors, ix, 140, 141, 145, 511 Drug abuse, see also Alcohol and drug abuse; Addiction Drug interactions, 122, 269, 570 Drug treatments, 2, 9, 17, 25, 29–30, 82, 95–116, 121 see also Chewing gum; Medical devices; Nicotine replacement therapy; Oral/nasal sprays; Psychotrophic drugs; Patches adolescents, 112, 116 antagonists, 4, 106–108, 110, 116, 244 mecamylamine, 107, 124, 266 antidepressants, 4, 104, 106, 124; see also Bupropion antihypertensive drugs, 107, 108–109 clonidine, 4, 108–109, 124 behavioral therapy and, 96, 115, 118–119 carbon monoxide, reduction of, 110, 113, 114 cardiovascular disease and, 110, 113, 114 committee charge, 3–4, 31–32, 33, 34, 142, 202–203, 205 cost of, 110 cotinine, 109–110, 114 definitional issues, 27, 28 Food and Drug Administration, 29–30, 205, 226–228 bupropion, 123–124, 172, 552–553 Investigational New Drug, 122, 215 historical perspectives, 95 mortality reduction, 111, 112–113 nicotine receptors, 97, 103, 105, 106–107, 110 over-the-counter drugs, 31, 94, 96, 97, 102, 110, 120, 123, 263 pregnant women, 116 relapse into smoking, 111 withdrawal, 96, 101, 104–114 (passim), 123 DSM, see Diagnostic and Statistical Manual of Mental Disorders Dye exclusion tests, 292 E Eclampsia, see Preeclampsia Eclipse, 4, 65, 94–95, 129, 215, 517–518, 602 Economic factors, see Cost and cost-benefit factors; Funding; Socioeconomic status; Taxation Education, see Labeling; Public education Educational attainment, 390, 425, 530, 543, 547, 564 Emphysema, see Chronic obstructive pulmonary disease Employment factors, see Workplace Endometrial cancer, 368, 421–422 Endothelial function, 161–162, 168, 169, 302, 354 cardiovascular disease, 479, 480, 481, 484–485, 486, 490, 491, 492

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction Nicorette, 97, 123, 129 Nicotine, vii, 25, 26, 28–29, 66, 67, 597 see also Addiction; Filters; Low-yield products; Nicotine replacement therapy; Pharmacology; Potential reduced-exposure products (PREPs); Ventilation antagonists, 4, 106–108, 110, 116, 244 antibodies, 107–108 antidepressants, 105 biomarkers, 323, 324–325, 326, 347 see also Cotinine plasma markers, 99, 113, 250, 293 body weight, 126, 158–159, 162, 255, 267, 270, 568–569 carcinogenesis, 167, 402, 403, 405 cardiovascular disease, 168, 470–471 nicotine replacement therapy (NRT), 98–99, 112, 115, 252–253, 471 cigarette-like products, 94, 95 cognitive effects, 254, 255, 259, 270, 564 compensatory smoking, 2, 26, 67, 88, 121, 164, 219, 266, 285, 322, 380, 402, 403, 405, 477, 517 definitional issues, 27, 126 dementia, 564 gender factors, 74 marketing factors, 61 mecamylamine, 107, 124, 266 metabolism, 109, 110, 116, 162, 248–252, 256, 269, 313, 422 processing of tobacco, 85 public understanding of content, 60 regulatory issues, 10, 207, 210, 211–212 receptors, 550, 564, 568 drug treatments, 97, 103, 105, 106–107, 110 genetic predisposition to smoking, 347–348 pharmacology, 161, 245, 252, 254, 255, 257 reproductive and developmental effects, 172, 545, 550, 552, 554–555, 572 smoker knowledge of, 72–73 surveillance, 184, 189 yield assessment, 88, 90, 184, 207, 210, 211–212, 317–319, 373 Nicotine replacement therapy (NRT), viii, 1, 3, 4, 29, 51–53, 95–104, 110–115, 161–162, 231, 233–234, 254, 263, 269, 270–271, 325, 326, 430, 533, 552–553, 554–555 see also Chewing gum; Oral/nasal sprays; Patches addiction, 161 behavioral therapy and, 96, 115 cardiovascular disease, 98–99, 112, 115, 252–253, 471 clinical trials, 96, 101–103, 113–115, 533 cost of, 101–102, 129, 554–555 dose-response relationship, 255–256, 264, 266 doses per day, 98, 105–106, 113, 248 gastrointestinal system, 267, 270 gender factors, 267–268 genetic factors, 270 historical perspectives, 113, 599, 601 labeling, 123 relapse into smoking, 101, 111, 115 reproductive and developmental effects, 112, 116, 172–173, 267, 552–553, 554–555 research methodology, 101–103 research recommendations, 269–271 risk perception, 110–111, 112 time factors, blood concentrations, 99–101, 103 FDA approval, 123 long-term use, 115, 121 Nicotrol Nasal Spray, 97, 124, 129 Nitrosamines, 4, 67, 86, 87, 91–92, 93, 148, 151, 210, 215, 294, 300, 301, 319, 326–327, 328, 348, 373–374, 376–377, 379, 380, 403, 405, 429–430, 603, 604 environmental tobacco smoke, 424 racial/ethnic differences, 406, 407 smokeless tobacco, 4, 93, 428, 429 Nonneoplastic respiratory diseases, 170–171, 500–542 see also Chronic obstructive pulmonary disease asthma, 170, 500–501, 518–525, 527, 530–531, 551 biomarkers, general, 170–171, 501–503, 506, 507, 512, 517, 527, 531, 532 urine, 503, 506, 523, 524, 525, 529, 531

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction bronchi, 24, 156, 500, 505, 514, 520, 522, 526, 551 bronchitis, 21, 295, 338, 502, 503, 505, 510, 525, 529, 551 epithelium, 298, 375, 376, 393 children, 500, 501, 506, 508, 510–511, 518–526 (passim), 528–530, 551 clinical research, 13, 171, 511–512, 514, 518, 522, 523–525, 529, 530, 532–533 cotinine, 517, 523, 525, 526, 529, 530, 532 dose-response relationship, 170, 171, 510–514, 521, 523, 527–528, 531, 532 environmental tobacco smoke (ETS), 500, 509–511, 521–522, 528–530, 531, 551 genetic factors, 170, 501–502 historical perspectives, 500, 506, 598, 599 immune system, 526, 527 incidence, 500, 518, 519, 526 infections, 170, 296, 297, 354, 500–501, 502, 506, 508, 516, 525–530, 532, 546, 547 children, 501, 506, 526, 528–529, 551 influenza, 297, 502, 526, 530 pneumonia, 501, 502, 526, 527–528, 529, 530, 551 surrogate markers, 507, 512 tuberculosis, 501, 526, 528 sputum, 12, 193–194, 313, 353–354, 391, 435, 437, 503, 505, 514, 515 Nortriptyline, 4, 104, 106, 124 Nurses’ Health Study, 168, 487, 567 O Occupational factors, see Workplace Ocular disease, 174, 193, 565–566 Oncogenes, 294, 341–342, 371, 389, 391, 393 Oral/nasal sprays, vii, 4, 94, 97–101, 103, 124, 266 Oropharyngeal disease, 174, 563–564, 574 see also Smokeless tobacco biomarkers, 156, 333, 338–339, 342 cancer, 23, 167, 301, 333, 342, 368, 372, 415–418, 425, 427–429, 597 gingivitis, 563–564 gum bleeding, 156, 338, 563 oral clefts, 549–550 Orthopedic effects, 565 osteoporosis, 158, 174, 176, 193, 338–339, 565, 574 rheumatoid arthritis, 174, 562 Over-the-counter drugs, 31, 94, 96, 97, 102, 110, 120, 263 FDA approval process, 123 P Packaging, 27, 30–31, 70, 77, 124 see also Labeling Palladium, 90–91 Pancreatic cancer, 372 Paper, 27, 85, 87, 88, 89, 91, 92, 128, 287, 571, 604 see also Ventilation cigarette defined, 82, 83 regulatory issues, 210, 224, 225 ventilation, 26, 71, 87, 88, 89, 90, 121, 211, 286, 287, 317, 380, 399, 595, 597 Parental factors, see Family/home factors Parkinson’s disease, 162, 270, 347, 571–572 Particulates, viii, 284–285, 286–287, 322 see also Aerosols carcinogens and mutagens, 148, 374, 436 free radicals, 378 immune response, 297–298 smoke yields, 87 Passive smoking, see Environmental tobacco smoke Patches, vii, 3, 4, 29, 96, 97, 98, 99, 100, 101, 103, 104, 112, 113, 601 clonidine, 108 mecamylamine, 107 pharmacokinetics, 246 Peptic ulcers, 175, 560–561, 573 Periodontal disease, see Oropharyngeal disease Pharmaceutical products, see Chewing gum; Drug treatment; Oral/nasal sprays; Nicotine replacement therapy; Psychotrophic drugs; Patches Pharmacology, 101, 161–163, 215, 243–282, 570, 583, 593 see also Addiction; Receptors alcohol, 253, 570 animal models, 244, 253, 258, 268 cardiovascular effects, 471 cotinine, 248, 249, 250, 265 historical perspectives, 243, 593–595, 597 regulatory issues, 126, 127

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction risk assessment, 161–163 withdrawal, 161, 244, 245, 254–260 (passim), 263–267 (passim) Philip Morris, 184, 584 Accord, 4, 65, 95, 603 NEXT, 29, 91 Pipe smoking, 85, 321, 473, 508, 597 Placental complications, 268, 545–547, 552 Plasma markers, 325, 480 cotinine, 348 leptin, 268, 378–379 nicotine, 99, 113, 250, 293 Platelet activation, 12, 156, 157, 168, 169, 252, 253, 296, 337–339, 343, 354, 479, 480, 481, 483–486, 490–491, 492, 493, 561 Pneumonia, 501, 502, 526, 527–528, 529, 530, 551 Policy, general, 7, 9, 38–39, 41–42, 51–56, 119–122, 176, 201–230 see also Automobile safety; Regulatory issues alcohol and drug abuse, 39–40, 46–50, 51, 52, 53, 55, 56, 601 automobile safety, vii, 41–44, 50, 52, 53, 56 surveillance, 197 taxation, 119, 128, 202, 596, 603 teen sexual behavior, 44 Political factors, 22 Polycyclic aromatic hydrocarbons (PAHs), 86, 148, 149, 295, 322, 326–327, 328–331, 333, 348, 374, 375–376, 377, 379, 391–392, 418, 570 Polymer chain reaction, 340, 391 Polymorphisms, 252, 256, 314, 315, 345, 346, 347, 405–406, 409, 478, 526 Potential reduced-exposure products (PREPs), 2, 3–17 (passim), 21, 53, 231, 232–240, 273, 574 see also Drug treatment; Filters; Low-yield products; Modified tobacco products; Nicotine replacement therapy; Ventilation additives, 144, 149, 165, 212 age factors, 76, 161, 164, 319, 321, 331 animal models, 144, 145, 147, 148–149, 162, 163, 165, 208, 212–213, 303, 350, 351, 384–386 behavioral effects of availability, 7, 73–76, 185, 197, 315 biomarkers, 142, 144, 145, 150–161, 162–163, 165, 237, 309–317, 323–352, 388, 435–436, 553 committee charge and methodology, 3–5, 31–32, 33, 34, 142, 202–203, 205, 237 currently available and novel, 91–95 definitional issues, 3, 28, 205 dose-response relationship, 14, 15, 33, 34, 140, 141, 144–147, 152, 154, 156, 158, 159, 160, 167, 237–238, 271, 310, 312, 325, 326, 352, 381, 395–396 epidemiology, 6, 7, 8, 10, 13–14, 141, 142, 147, 153, 160, 165, 193, 195, 197, 203, 206, 208, 221, 222, 229, 232, 236, 238, 437–438, 584 FDA actions, 15, 122–124, 129–130, 141, 181, 204–205, 206, 209, 221, 226–227 Federal Trade Commission (FTC), 2, 15, 26, 61, 67, 207, 210, 221, 227, 350 historical perspectives, 24, 26, 55, 60–81, 88–91 incidence of disease, 5–6, 193 in vitro assays, 12, 34, 144, 148–149, 151, 152, 154, 156, 158, 160, 168, 208, 212, 215, 303, 350, 351 cancer, 154, 167, 367, 383–384, 385, 432 lung cancer, 294–295, 395–399, 407–409 marketing, 61–66 other harm reduction intervention compared, 50–53 policy, general, 202–204 postmarket surveillance, x, 182, 184, 189, 190, 203, 207, 208, 213, 221–222, 270 pregnant women, 173–174, 552–553, 554–555 prevalence of use, 67 product descriptions, 82–140 regulation, 5, 6, 7–11, 30–32, 33, 122–124, 129–130, 147, 202–229 (passim), 234–235, 236, 238 relapse into smoking, 75, 101, 111, 115, 141, 146 risk assessment, general, 140–179 (passim) risk thresholds, 9, 164, 167, 222–224, 225–226, 431, 439, 480, 481, 487

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction risk perception, 26, 68–69, 77, 78 smokeless tobacco, 93 Surgeon General’s reports, 24 surveillance, x, xi, 7–8, 10, 13–14, 147, 162, 176, 181, 182, 183, 185, 189, 203, 208, 221–222, 225, 236, 237, 238, 269, 270, 573, 574 time requirements for evaluation, 5, 141, 146, 147, 232, 320 toxicology, 144, 145, 147–150, 204–205, 207, 208–209, 212–213, 228, 292, 302–303 Preeclampsia, 268, 560, 572 Pregnancy, 53–54, 543–555 see also Reproductive and developmental effects alcohol use, 172, 545, 547 animal models, 13, 298 biomarkers, 174, 191, 545, 548, 553, 570, 572 birthweight, 11, 23, 24, 149, 172, 173–174, 188, 193, 212, 267, 340–341, 344, 529, 543, 547–549, 550, 551, 552, 554, 596 bupropion, 172, 174, 552–553, 554 carbon monoxide, 172, 173–174, 549, 550, 552, 554 cohort studies, 173, 547 contraceptives, 45, 477, 481, 544, 597 cotinine, 545, 548, 553, 572 diet, 547 drug treatments, 116 environmental tobacco smoke (ETS), 544, 545, 548, 549, 551 fetal lung development, 149, 298, 511, 551 hemoglobin, 546, 549 nicotine, 172, 545, 550, 552, 554–555, 572 nicotine replacement therapy (NRT), 112, 116, 172–173, 267, 552–553, 554–555 placental complications, 268, 545–547, 552 preeclampsia, 268, 560, 572 PREPs, 173–174, 552–553, 554–555 preterm delivery, 172, 543, 546–547, 552, 596 regulatory issues, 10–11, 208, 222 smokeless tobacco, 301–302, 551–552 spontaneous abortion, 11, 24, 268, 545, 554, 596 teenage, 44, 172, 543, 545, 552 surveillance, 187–188, 191, 193 teratogenic effects, 545, 554–555 Pregnancy Risk Assessment Monitoring System, 187–188 Premarket notification/testing/approval, x, 8, 129, 213–215, 217, 223–224, 227–228 Premier, 4, 93, 94, 600 PREPs, see Potential reduced-exposure products President’s Cancer Committee, 211 Prevalence, 195, 262, 594, 603 see also Incidence adolescents, 1, 22, 38, 319 birthweight, low, 11, 23, 24, 149, 172, 173–174, 188, 193, 212, 267, 340–341, 344, 529, 543, 547–549, 550, 551, 552, 554, 596 cigar smoking, 425 gender factors, 22, 74, 87, 404 harm reduction defined, 40 orthopedic effects, 565 PREP use, 67 respiratory infections, 529 smokeless tobacco use, 92–93, 427 smoking, general, viii, 1, 22, 23, 25, 74, 189, 191, 197, 414 antidepressants, 106 international perspectives, 23, 88–89 nicotine replacement drugs, clinical trials, 102–103 pregnant women, 543–544 Processing of tobacco, 66, 82, 84–87, 89, 90–91, 299–300, 597 see also Additives blending, viii, 26, 82, 85, 87, 94, 128, 209, 287 curing, 8, 82, 83, 84, 91, 128, 189, 209, 300 FDA regulation, 128 regulation recommendations, 209 surveillance, 189 Proteomics, 12–13, 152, 314, 334, 353, 389, 492 Psychological factors, 118 see also Attitudes and beliefs; Behavioral effects of tobacco use; Behavioral treatments; Dementia; Depression; Schizophrenia addiction, 41, 118, 161, 254, 256–257, 259

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction adolescents, 74 anxiety, 109 depression, 104, 174, 186, 256–257, 347, 568–569 antidepressants, 105–106, 115–116, 254, 256, 570 menthol cigarettes, 73 nicotine mood enhancement, 245, 254 nicotine replacement therapy, addiction, 161 surveillance, 186 Psychotrophic drugs, vii, 268–269 FDA attempt to regulate tobacco, 126 Public education, x, 9, 203–204, 236, 603 see also Internet; Schools committee charge, 4–5 consumer information, 7, 231, 240 see also Labeling regulatory framework, 204, 205, 225, 229 surveillance, 188 Public Health Cigarette Smoking Act, 125 Public Health Service, 102, 103, 109, 595 Public health, general, 4, 5, 6, 7, 14, 16, 25, 31, 33, 141, 142, 202, 235–237 see also Cessation programs; Epidemiology; Fires; Policy, general; Surveillance restrictions on public smoking, 120, 206, 225, 597, 599, 600, 601 Pulmonary system, see Respiratory system R Race/ethnicity, 73, 86, 233, 321, 543, 548 see also specific groups birthweight, 548 cancer, 406–408, 416, 436 dementia, 564 dose-response relationship, 164, 407 metabolic processes, 250, 270–271, 389 nitrosamines, 406, 407 oropharyngeal disease, 416 pregnant smokers, 543, 553 prevalence of smoking, 22, 24 Surgeon General’s reports, 24, 125, 603 Radon, 195, 298, 408 Receptors, 108, 244, 482, 485–486, 550–551, 564, 568 see also Neurotransmitters dopamine, 256, 266, 347–348 estrogen, 394, 405 nicotinic, 550, 564, 568 drug treatments, 97, 103, 105, 106–107, 110 genetic predispositions for smoking, 347–348 pharmacology, 161, 245, 252, 254, 255, 257 progesterone, 405 Red Book, 14, 15, 33, 34, 141 Regulatory issues, x, 6, 30–31, 201–229, 584 see also Enforcement; Federal Trade Commission; Food and Drug Administration; Labeling; Legislation; Standards additives, 128, 149, 209, 210, 212, 224–225 advertising, 7, 10, 120, 125–126, 127, 128, 141, 203, 206, 207, 208, 211, 216–221, 222, 229, 232, 595, 597, 602, 603 animal models, 10, 208, 212–213, 215 automobile safety, vii, 41–44, 50, 52, 53, 56 biomarkers, 10, 11–12, 207–208, 211, 220, 348–349 carbon monoxide, 210, 218 carcinogens, 10, 208, 215 clinical trials, 122, 208, 209, 212, 213, 215, 227, 229 committee charge and methodology, 4, 5, 31–32, 34, 202–203 consumer information, general, 204, 205, 225, 229 conventional tobacco, 124–130, 207, 209–229 (passim), 234–235 definitional issues, 11, 27–28, 30, 124, 126, 205, 225–226 enforcement, 11, 30, 40, 43–44, 48, 120, 125, 196, 207, 209, 226, 238, 239 epidemiology, 8, 10–11, 129, 203, 206, 207, 208, 221, 222, 229 exposure, general, 10, 204, 207–208, 215 filters, 128, 210, 225 historical perspectives, 124–130, 595–604 marketing, 207, 208, 213, 215, 216–221, 222–223, 228, 229, 232 see also “advertising” supra; Labeling postmarket surveillance, x, 182, 184, 189, 190, 203, 207, 208, 213, 221–222, 270

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction premarket testing/approval, x, 8, 129, 213–215, 217, 223, 224, 227–228 medical devices, 30, 91, 124, 125–126, 127, 128, 129, 204, 205, 206, 209–210, 214, 225, 228 modified tobacco products, 8, 10–11, 205, 206, 207, 209 mortality, 213, 215, 220 nicotine, 10, 207, 210, 211–212 paper, 210, 224, 225 pharmacology, 126, 127 PREPs, 5, 6, 7–11, 30–32, 33, 122–124, 129–130, 147, 202–229 (passim), 234–235, 236, 238 principles, 10–11, 17 processing of tobacco, 189, 209 public smoking restrictions, 120, 206, 225, 597, 599, 600, 601 reproductive and developmental effects, 10–11, 208, 222 respiratory effects, 10, 208, 215, 222 smokeless tobacco products, 126, 128, 209 surveillance, 183, 184, 188, 189, 190, 197, 203, 204, 208, 221–222, 225 taxation, 119, 128, 202, 596, 603 toxicology, 9, 10–11, 128, 204–205, 207, 212–213, 222, 224–225, 228 yield assessment, 183, 184, 207–208, 210–212, 219 smoking machines, 2, 3, 26–27, 87–88, 90, 210–211, 226, 283–284, 317–319, 350, 352, 373, 380, 395, 404 Relapse, 5, 40, 141, 262 alcohol abuse, 47 depression and, 104 drug treatment and, 111 low-yield cigarettes, 75 nicotine replacement products, 101, 111, 115 PREP risk assessment, 75, 101, 111, 115, 141, 146 risk perception and, 41 substance abusers, 49 Renal disease, 481, 567–568 Reproductive and developmental effects, 4, 24, 172–174, 268, 298, 302, 543–559, 598, 601 see also Age factors; Genetic factors; Pregnancy animal models, 13, 298 behavioral/cognitive disorders, 268, 550–551 biomarkers, 174, 191, 545, 548, 553, 570, 572 serum, 548, 553, 570, 572 urine, 545, 548, 553 birthweight, 11, 23, 24, 149, 172, 173–174, 188, 193, 212, 267, 340–341, 344, 529, 543, 547–549, 550, 551, 552, 554, 596 carbon monoxide, 172, 173–174, 549, 550, 552, 554 cervical cancer, 24 clinical research, 173–174, 547, 548, 554 cognitive and behavioral disorders, 268, 550–551 congenital malformations, 268, 545, 549–550 contraceptives, 45, 477, 481, 544, 597 environmental tobacco smoke (ETS), 544, 545, 548, 549, 551 fertility, 173, 267, 544–545 menstrual cycle, 267 nicotine, 172, 545, 550, 552, 554–555, 572 nicotine replacement therapy (NRT), 112, 116, 172–173, 267, 552–553, 554–555 pelvic inflammatory disease, 544–545 PREP risk assessment, 172–174, 552–553, 554–555 regulatory issues, 10–11, 208, 222 research recommendations, 553–555 smokeless tobacco, 551–552 sudden infant death syndrome, 173, 268, 543, 546, 549, 552, 596 surveillance, 187–188, 193 teratogenic, 545, 554–555 Research methodology, 55–56, 121–122, 438–439 see also Animal models; Biomarkers; Clinical research; Cohort studies; Epidemiology; Internet; In vitro assays; Surveillance addiction measures/models, 257–267 asthma studies, 520, 521 carcinogenesis, 378, 379–394, 410, 434–439 committee study at hand, 3–5, 16, 31–35, 142 dementia, 564–565 exposure, 309–366 see also “smoke yields” infra

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction forced expiratory volume (FEV), 156, 171, 338, 343, 503, 506, 508–509, 514–515, 516, 520, 523, 532–533 free radical carcinogens, 378 health impact research, 66–67 nicotine metabolism, 252 nicotine replacement drugs, 101–103 Parkinson’s disease, 572 quitting smoking, 76 respiratory infections, 529–530 risk perception, 68 smoking machines, 2, 3, 26–27, 87–88, 90, 210–211, 226, 283–284, 317–319, 350, 352, 373, 380, 395, 404 Research recommendations, 7–17, 33–35, 77–78, 203, 206–207, 232–233, 239–240, 573–574 biomarkers, 352–355, 438, 491 cancer, 434–439 cardiovascular, 491–493 nicotine replacement therapy, 269–271 nonneoplastic respiratory diseases, 532–533 reproductive and developmental effects, 553–555 smokeless tobacco, 301–302 toxicology, 301–303 Respiratory system, 4, 156, 285–286, 343 see also Nonneoplastic respiratory diseases bronchi, 24, 156, 500, 505, 514, 520, 522, 526, 551 bronchitis, 21, 295, 338, 502, 503, 505, 510, 525, 529, 551 cancer and carcinogenesis, 285, 298, 375, 376, 391, 392, 393, 437, 518 epithelium, 298, 375, 376, 393 bronchoalveolar lavage, 13, 156, 295, 338–339, 343–344, 437, 517 bronchoscopy, 157, 171, 339, 392, 502–503, 517, 531 epithelial function, 500, 519, 525–526 bronchial, 298, 375, 376, 393 forced expiratory volume (FEV), 156, 171, 338, 343, 503, 506, 508–509, 514–515, 516, 520, 523, 532–533 gender factors, 416, 520 chronic obstructive pulmonary (COPD), 500, 509, 512, 514, 515, 516 lung cancer, 24, 401, 402–403, 404–406, 410, 411, 412, 413, 598, 599 inflammation, 12, 13, 95, 113, 149, 156, 170–171, 295, 298, 302, 338, 343–344, 395, 502, 505, 506, 507, 516–518, 527, 531, 533 asthma, 170, 500–501, 518–525, 527, 530–531, 551 lung cancer, viii, 21, 23, 24, 66, 67, 86, 89, 149, 166–167, 192, 193, 215, 293–295, 296–297, 302, 333, 342, 355, 368, 372 nicotine pharmacology, 244–245, 246 regulatory issues, 10, 208, 215, 222 Rheumatoid arthritis, 174, 562 Risk assessment, general, ix-x, 14, 15, 33–35, 66–67, 239–240 see also Biomarkers; Dose-response relationship; Epidemiology; Exposure; Surveillance; specific diseases and anatomical systems age factors, 67, 145, 186, 321 committee charge, 3–4 definitional issues, 28 exposure-to-adverse effect, time, ix, 140, 145, 166, 511, 530 filters, 143, 164, 168, 399–400, 402–404 gender factors, 67, 145, 164, 168 genetic predisposition to toxic effects, ix, 6, 13, 145, 153, 164, 166, 192, 233, 344–347, 390, 408–409, 416, 429, 436, 478, 490, 508 low-yield products, 143, 145, 164, 399–400 modified tobacco products, viii pharmacology, 161–163 PREPs, 140–179 (passim) risk thresholds, 9, 164, 167, 222–224, 225–226, 431, 439, 480, 481, 487 tobacco, 141–144 Risk characterization, general, 14, 33–34, 140, 237–238, 239 Risk perception, 2, 6, 8, 10, 26, 28, 40–41, 42–43, 67–73, 76–77, 185–188 (passim), 212, 434, 584 addiction, 68 additives, 72–74, 77 adolescents, 41, 68, 72, 73–74, 112, 185 carbon monoxide, 72–73 international perspectives, 72–73 low-yield products, 66–67, 68–71, 76–77

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction negative attitudes toward unsafe behavior, general, 43 nicotine replacement products, 110–111, 112 R.J.Reynolds, 184, 585, 594, 595, 597, 600 Eclipse, 4, 65, 94–95, 129, 215, 517–518, 602 Premier, 4, 93, 94, 600 Winston, 72, 91 RNA, 152, 153, 299, 314, 334, 353, 389 S Saliva, 209, 267, 300, 311, 323, 325, 422, 428, 523, 525 Schizophrenia, 162, 174, 244, 257, 268–269, 347, 568 Schools impacts of smoking on performance, 187 prevention/cessation programs, 24, 120, 598, 601 teen sexual behavior, 44–45 Youth Risk Behavior Survey, 93, 185–187, 261, 320–321 Secondary smoke, see Environmental tobacco smoke Serotonin, 105, 109, 244, 347, 478, 551 Sertraline, 105 Serum markers, 157, 174, 184–185, 187, 190, 300, 313, 314, 321, 323, 330, 335, 339, 353 cancer, 333, 422 cholesterol levels, 289, 296, 477, 482 diabetes, 567 environmental tobacco smoke, 348, 422 nonneoplastic respiratory diseases, 506, 517, 527, 532 reproductive and developmental effects, 548, 553, 570, 572 Sex differences, see Gender factors Sexual behavior, adolescents, 44–46, 50, 51 pregnancy, 44, 172, 543, 545, 552 Sidestream smoke, see Environmental tobacco smoke Skeletal system, see Orthopedic effects Skin diseases, see Dermatologic diseases Skin patches, see Patches Sleep disturbance, 105, 106, 254, 255 Smith Kline Beecham, 585 Smokeless tobacco products, 83, 85, 92–95, 99, 101, 149, 167, 255, 426–429, 563, 598, 600 see also Chewing tobacco; Snuff addiction, 266 additives, 299–300 adolescents, 302 advertising, 93 age factors, 93, 302 cancer, 4, 93, 300–301, 426–429 epidemiology, 301 international perspectives, 93, 300, 426–428 snus, 4, 14, 167, 204, 270, 300, 301, 302, 427, 428, 434 nitrosamines oral disease, 167, 563 prevalence of use, 92–93, 427 regulation of, 126, 128, 209 research recommendations, 301–302 toxicology, 299–302 use surveys, 321 Smoking machines (Federal Trade Commission), 2, 3, 26–27, 87–88, 90, 210–211, 226, 283–284, 317–319, 350, 352, 373, 380, 395, 404 Smoking topography, 151, 182, 322, 323, 349, 352, 399, 405, 406, 407–408, 437 see also Inhalation depth and topography compensatory smoking, 2, 26, 67, 88, 121, 164, 219, 266, 285, 322, 380, 402, 403, 405, 477, 517 Snuff, 83–84, 92–93, 100, 300, 301, 427, 593 DNA adducts, 332 snus, 4, 14, 167, 204, 270, 300, 301, 302, 427, 428, 434 Socioeconomic factors asthma, 519 educational attainment, 390, 425, 530, 543, 547, 564 lung cancer, 407, 414 pregnant smokers, 543, 547 Spontaneous abortions, 11, 24, 268, 545, 554, 596 Sprays, see Oral/nasal sprays Sputum, 12, 193–194, 313, 353–354, 391, 435, 437, 503, 505, 514, 515 Standards, 11, 17, 30–31, 209, 225–226 see also Definitional issues; Regulatory issues

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction addiction, 255, 257–262 (passim), 265 additives, 224–225 biomarkers, 348–349 Diagnostic and Statistical Manual of Mental Disorders (DSM), 255, 257, 258–259, 260–262 fire-safe cigarettes, 87, 571 International Diagnostic Code, 257, 258–259 International Standards Organization, 87, 283 medical devices, 124, 228 pregnant women, clinical guidelines, 172 risk thresholds, 9, 164, 167, 222–224, 225–226, 431, 439, 480, 481, 487 smoke yields, 87–88, 210–212, 283–284 smoking machines, 2, 3, 26–27, 87–88, 90, 210–211, 226, 283–284, 317–319, 350, 352, 373, 380, 395, 404 tobacco industry regulation, 128, 204 Star Scientific (Star Tobacco), 91–92, 585, 603, 604 Advance, 4, 92 Stroke, 24, 168, 470, 473, 476, 487, 489, 600 Sudden infant death syndrome, 173, 268, 543, 546, 549, 552, 596 Surgeon General, 21–26 (passim), 69, 125, 379, 380–381, 513, 595–603 (passim) Surgery, 438 cardiovascular, 473, 476 inflammatory bowel disease, 561–562 lung cancer, 395 Surgical wounds, see Wound healing Surrogate markers, 6, 11–12, 16, 31, 147, 153, 235, 270, 310, 314, 335, 339 cancer, 166, 327, 330, 435–436 cardiovascular disease, 168, 483–486, 490 nonneoplastic respiratory disease, 507, 512 regulatory issues, 220 Surveillance, 10, 17, 176, 180–200, 203, 208, 232, 573, 574 see also Centers for Disease Control and Prevention; Epidemiology additives, 189, 196 adolescents, 185, 192 age factors, 185, 186, 191, 192, 194, 321 attitudes and beliefs, 8, 10, 185–188 (passim), 192, 196, 197 behavioral effects of smoking, 183, 185–188, 191–192, 195, 197 carbon monoxide, 184 clinical research and, 183, 193, 197 cost of, 181, 195 cotinine, 184–185, 187 defined, 180, 181, 194 dependence potential, 269 environmental tobacco smoke (ETS), 194 FDA, 181 Federal Trade Commission (FTC), 183, 184, 189, 190 filters, 183, 189 gender factors, 187 national surveillance system, general, 8, 181, 207 pregnant women, 174, 553 postmarket surveillance, x, 182, 184, 189, 190, 203, 207, 208, 213, 221–222, 270 PREPs, x, xi, 7–8, 10, 13–14, 147, 162, 176, 181, 182, 183, 185, 189, 203, 208, 221–222, 225, 236, 237, 238, 269, 270, 573, 574 regulatory issues, 183, 184, 188, 189, 190, 197, 203, 204, 208, 221–222, 225 time factors, 181, 194 yield assessments, 182, 183, 184 Sweden, 4, 14, 93, 167, 204, 270, 300, 301, 302, 427, 428, 434, 548 Synergistic effects, 298, 342, 378, 387, 390, 570 see also Air pollutants alcohol and tobacco, 342, 415–416, 418, 426, 428 asbestos, 89, 298, 408, 501, 599 bladder cancer, 420 chronic obstructive pulmonary disease (COPD), 508–509 cardiovascular disease, 477–478 drug interactions, 122, 269, 570 lung cancer, 408–409 oropharyngeal disease, 415–416, 418 pregnancy, 545 T Tar, 2, 11, 24, 26, 66, 67, 70–71, 184, 584 see also Filters; Low-yield products; Potential reduced-exposure products (PREPs); Ventilation

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction carcinogenesis, 373–374, 399–404, 407 cigarette-like products, 94 marketing factors, 61, 65 public understanding of content, 60 yield assessment, 87, 90, 91, 92, 94, 184, 210, 211–212, 317–319, 373–374, 399–401, 407 Taxation, 119, 128, 202, 596, 603 T cells, see Lymphocytes Technological innovations see Drug treatments; Filters; Fire-safe cigarettes; Modified tobacco products; Potential reduced-exposure products (PREPs); Ventilation automobile safety, 41, 42, 43 FTC smoking machine, 2, 3, 26–27, 87–88, 90, 210–211, 226, 283–284, 317–319, 350, 352, 373, 380, 395, 404 processing of tobacco, 66 Teenagers, see Adolescents Temperature factors, viii, 95, 210, 284 definition of cigarette, 27 Teratogenic effects, 545, 554–555 Thrombosis, 154, 157, 336–337, 339, 356, 481, 485–486, 491, 493 Time factors addiction, 255–256, 260, 262, 263–264 adverse effects of treatment, 121 behavioral treatments, 117–118 biomarkers, half-life, 152, 154, 156, 157, 158, 250, 297, 316, 323, 324, 328, 333, 376, 422 burn rate, 87 chronic obstructive pulmonary (COPD), 503, 511–512 committee charge, 4 dose-response assessment, 140, 141 duration of smoking, lifetime, 67, 76, 151, 168, 390, 395, 396–397, 401, 402, 404, 419, 420, 471, 493, 508, 566, 572 duration of smoking cessation, 75, 115, 186, 409–415, 419, 438, 470, 473, 475, 476, 487, 490, 562 see also Relapse exposure-to-adverse effect, ix, 140, 145, 166, 511, 530 FDA approval for medical devices, 124 legislation, 221 nicotine pharmacology, 246, 250, 251, 255–256 nicotine replacement drugs, blood concentrations, 99–101, 103 FDA approval, 123 long-term use, 115, 121 population surveys, 320 PREP evaluation, 5, 141, 146, 147, 232, 320 reproductive effects, time to conception, 544 surveillance, 181, 194 thrombosis bleeding, 154, 336 withdrawal symptoms, 255 wound healing, 174, 175, 194, 561, 573 Tobacco Testing Laboratory, 600 Toluene, 89, 148, 290, 374 Toxicology, 26–28, 34, 121, 129, 147–148, 283–308, 553, 583 see also Animal models; Biomarkers; Carbon monoxide; Dose-response relationship; Exposure; Synergistic effects; Tar; Yield assessment advertising and, 66 arsenic, 72, 148, 184, 374 asbestos, 89, 298, 408, 501, 599 cyanide, 72, 89, 291, 324–325, 401, 549, 561, 572 environmental tobacco smoke, 283, 285, 287, 289–290 filters, 284, 287 genetic susceptibilities, ix, 6, 13, 145, 153, 164, 166, 192, 233, 344–347, 390, 408–409, 416, 429, 436, 478, 490, 508 nicotine-derived, 28–29, 86, 94–95, 111-112, 173–174, 207, 270, 429–430, 554 reproductive and developmental effects, 172, 545, 550, 552, 554–555, 572 PREP risk assessment, 144, 145, 147–150, 204–205, 207, 208–209, 212–213, 228, 292, 302–303 processing of tobacco, 85, 128 regulatory issues, 9, 10–11, 128, 204–205, 207, 212–213, 222, 224–225, 228 research recommendations, 301–303 susceptibility to toxic effects, ix, 6, 13, 145, 153, 164, 166, 192, 233, 344–347 smoker knowledge of, 72–73, 77

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Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction smoking machines, 2, 3, 26–27, 87–88, 90, 210–211, 226, 283–284, 317–319, 350, 352, 373, 380, 395, 404 standards, 204, 283–284 Toxic Substances Control Act, 125 True, 26, 64 Tuberculosis, 501, 526, 528 U Ulcers, see Peptic ulcers Urine biomarkers, 12, 106, 109, 156, 157, 171, 190, 250, 252, 295, 312, 313, 314, 325, 326, 336–337, 339, 343, 346 cancer, 326, 353–354, 376, 378, 407, 420–421, 422, 424, 429, 435, 437 cardiovascular disease, 485, 486 environmental tobacco smoke, 323, 348 nonneoplastic respiratory diseases, 503, 506, 523, 524, 525, 529, 531 reproductive and developmental effects, 174, 545, 548, 553, 548 V Vapors, 27, 87, 88, 92, 94, 148, 284, 374 Vascular activation, 12, 157, 169, 269, 337, 480, 490–491, 493 Vascular disease, see Cardiovascular disease; Extracardiac vascular disease Ventilation asthma, 522 chronic obstructive pulmonary (COPD), 503, 510 cigarette paper, 26, 71, 87, 88, 89, 90, 121, 211, 286, 287, 317, 380, 399, 595, 597 respiratory infections, 526 Visual impairments, see Ocular disease Vitamin C, 486 Volatile organic compounds, 89, 148, 374 W Weight, see Birthweight; Body weight White persons, see Caucasians Withdrawal symptoms, 405, 569 drug treatments, 96, 101, 104–114 (passim), 123 nicotine pharmacology, 161, 244, 245, 254–260 (passim), 263–267 (passim) Women, see Gender factors Women’s Health Study, 544 Workplace occupational toxins, 33, 140, 151, 164, 166, 180, 195, 298, 329, 332, 350, 375, 377, 390, 408, 419, 420, 431, 433, 508, 599 smoking restrictions, 119–120, 422 World Bank, 23 World Health Organization, 23, 25, 258, 470 World Wide Web, see Internet Wound healing, 174, 175, 194, 561, 573 Y Yield assessment, 70–71, 87–88, 90, 92, 234, 284 see also Low-yield products carbon monoxide, 87, 88, 90, 92, 94, 95, 184, 210 nitrosamines, 376 particulates, 87 regulatory issues, 183, 184, 207–208, 210–212, 219 smoking machines, 2, 3, 26–27, 87–88, 90, 210–211, 226, 283–284, 317–319, 350, 352, 373, 380, 395, 404 surveillance, 182, 183, 184 tar, 87, 90, 91, 92, 94, 184, 210, 211–212, 317–319, 373–374, 399–401, 407 Youth Risk Behavior Survey, 93, 185–187, 261, 320–321 Z Zyban, 30, 104, 123–124 see also Bupropion

Representative terms from entire chapter:

regulatory issues