PRINCIPLES OF TOXICOLOGY

More documents

Recommendations

Info

TABLE 18.6 Estimated Average Loss of Life Expectancy from Various Risks, Activities, & Diseases Being an unmarried male Days Lost 3500 Smoking cigarettes and being male 2250 Heart disease 2100 Being an unmarried female 1600 Being 30% overweight 1300 Being a coal miner1100 Cancer980 Being 20% overweight 900 Having less than an 8th grade education 850 Smoking cigarettes and being female 800 Poverty 700 Stroke 520 Smoking cigars 330 Having a dangerous job 300 Smoking a pipe 220 Increasing your daily food intake 100 calories 210 Driving motor vehicle 207 Pneumonia, influenza 141 Alcohol addiction 130 Accidents in the home 95 Suicide 95 Diabetes 95 Homicide 90 Misusing legal drugs 90 Having an average-risk job 74 Drowning 41 Employment that entails radiation exposure 40 Falls 39 Walking down the street 37 Having a safer-than-average job 30 Fires and burns 27 Generation of energy 24 Using illegal drugs 18 Solid and liquid poisons 17 Suffocation 13 Firearm accidents 11 Natural radiation 8 Poisonous gases 7 Medical X-ray exposure 6 Drinking coffee 6 Oral contraceptives 5 Riding a bicycle 5 Drinking diet sodas 2 Nuclear reactor accidents 2 Radiation from the nuclear industry 0.02 Source: Allman (Oct. 1985). 18.8 COMPARATIVE RISK ANALYSIS 471
472 RISK ASSESSMENT TABLE 18.7 Activities Estimated to Increase Your Chances of Dying in Any Year by One in a Million Activity Cause of Death Smoking 1.4 cigarettes Cancer, heart disease Drinking 0.5 L of wine Liver cirrhosis Spending 1 h in a coal mine Black lung disease Spending 3 h in a coal mine Accident Living 2 days in New York or Boston Air pollution Traveling 6 min by canoe Accident Traveling 10 miles by bicycle Accident Traveling 150 miles by car Accident Flying 1000 miles by jet Accident Flying 6000 miles by jet Cancer from cosmic radiation Living 2 months in Denver on vacation from New York Cancer from cosmic radiation Living 2 months in average stone or brick building Cancer from natural radioactivity One chest X-ray taken in a good hospital Cancer from radiation Living 2 months with a cigarette smoker Cancer, heart disease Eating 40 tablespoons of peanut butter Liver cancer from aflatoxin B Drinking Miami drinking water for 1 year Cancer from chloroform Living 5 years at site boundary of a nuclear power plant Cancer from radiation Eating 100 charcoal-broiled steaks Cancer from benzopyrene Source: Allman (Oct. 1985). 18.9 RISK COMMUNICATION In order to be useful, risk assessment results must be effectively communicated to nontechnical audiences. This can include risk managers, legislators, the public, industry, and environmental groups. If risk managers don’t understand the results, it can lead to bad regulatory and policy decisions. Public understanding of risk assessment results is also essential if they are to participate in, or at least accept the results of, risk-based decision-making. Effectively communicating the results of risk assessments is an enormous challenge. Problems lie in virtually all aspects of the risk communication process, including (1) the individual, agency, or company that conducts and presents the risk assessment; (2) the risk assessment itself; (3) the means to convey risk information; and (4) the audience. Examples of these problems are listed in Table 18.8. One of the biggest hurdles is the fact that risk analyses are often very complex, technical exercises. Making the process and outcome of the risk analysis transparent to laypersons is next to impossible unless there is some opportunity to provide background education to “bring them up to speed” on the subject. In most situations, this opportunity doesn’t exist. The public is arguably one of the most important recipients of risk information, yet one of the most difficult audiences for risk assessors to communicate with. One problem is that the most common channel for communicating risk information to the public is through the news media. This presents at least three difficulties in trying to communicate a clear and accurate message: (1) reporting of the information may be biased, incomplete, or inaccurate; (2) news accounts may tend to sensationalize or focus on ancillary issues, such as disagreements between parties or human interest stories; and (3) news media have generally shown little interest in providing the background information needed to educate the public on risk analysis and to help them interpret findings for themselves. No doubt one reason why the media have not invested much effort in educating the public about risk assessment is that the public itself, for the most part, has shown little interest in the technical complexities and nuances of risk analysis. In most situations for which a risk assessment is needed, they just want a straight answer to the simple question, “Is it safe?” Anything other than a clear “yes” answer to this question signals cause for concern. Herein lies a second major problem for risk
Page 1 and 2:
PRINCIPLES OF TOXICOLOGY
Page 3 and 4:
This book is printed on acid-free p
Page 5 and 6:
vi CONTRI BUTORS PAUL J. MIDDENDORF
Page 7 and 8:
viii CONTENTS 4 Hematotoxicity: Che
Page 9 and 10:
x CONTENTS 12 Mutagenesis and Genet
Page 11 and 12:
xii CONTENTS III APPLICATIONS 435 1
Page 13 and 14:
PREFACE Purpose of This Book Princi
Page 15 and 16:
ACKNOWLEDGMENTS A text of this unde
Page 17 and 18:
PART I Conceptual Aspects Principle
Page 19 and 20:
4 GENERAL PRINCIPLES OF TOXICOLOGY
Page 21 and 22:
Page 23 and 24:
Page 25 and 26:
Page 27 and 28:
Page 29 and 30:
Page 31 and 32:
Page 33 and 34:
Page 35 and 36:
Page 37 and 38:
Page 39 and 40:
Page 41 and 42:
Page 43 and 44:
Page 45 and 46:
Page 47 and 48:
Page 49 and 50:
Page 51 and 52:
36 ABSORPTION, DISTRIBUTION, AND EL
Page 53 and 54:
Page 55 and 56:
Page 57 and 58:
Page 59 and 60:
Page 61 and 62:
Page 63 and 64:
Page 65 and 66:
Page 67 and 68:
Page 69 and 70:
Page 71 and 72:
3 Biotransformation: A Balance betw
Page 73 and 74:
BIOTRANSFORMATION: A BALANCE BETWEE
Page 75 and 76:
BIOTRANSFORMATION: A BALANCE BETWEE
Page 77 and 78:
Figure 3.5 Diagrammatic rendition o
Page 79 and 80:
3.2 BIOTRANSFORMATION REACTIONS The
Page 81 and 82:
TABLE 3.4 Important Cytochrome P450
Page 83 and 84:
Figure 3.8 Cytochrome P450-catalyze
Page 85 and 86:
oth of which are suitable for conju
Page 87 and 88:
TABLE 3.6 Changes in Rat Hepatic Dr
Page 89 and 90:
3.2 BIOTRANSFORMATION REACTIONS 75
Page 91 and 92:
TABLE 3.7 Induction of Xenobiotic-M
Page 93 and 94:
3.2 BIOTRANSFORMATION REACTIONS 79
Page 95 and 96:
pyridoxal phosphate depletion by th
Page 97 and 98:
Biotransformation: A Balance betwee
Page 99 and 100:
een shown to be responsible for the
Page 101 and 102:
4 Hematotoxicity: Chemically Induce
Page 103 and 104:
Figure 4.1 Formation of blood. Matu
Page 105 and 106:
TABLE 4.2 Leukemias and Lymphomas 4
Page 107 and 108:
4.3 THE MYELOID SERIES 93 to contra
Page 109 and 110:
function and response to stimuli, (
Page 111 and 112:
Hypoxia can result from a variety o
Page 113 and 114:
4.7 INORGANIC NITRATES/NITRITES AND
Page 115 and 116:
Exposure to aromatic amines can be
Page 117 and 118:
4.10 BONE MARROW SUPPRESSION AND LE
Page 119 and 120:
4.12 TOXICITIES THAT INDIRECTLY INV
Page 121 and 122:
4.15 ANTIDOTES FOR HYDROGEN SULFIDE
Page 123 and 124:
REFERENCES AND SUGGESTED READING 10
Page 125 and 126:
112 HEPATOTOXICITY: TOXIC EFFECTS O
Page 127 and 128:
Page 129 and 130:
Page 131 and 132:
Page 133 and 134:
Page 135 and 136:
Page 137 and 138:
Page 139 and 140:
Page 141 and 142:
Page 143 and 144:
130 NEPHROTOXICITY: TOXIC RESPONSES
Page 145 and 146:
Page 147 and 148:
Page 149 and 150:
Page 151 and 152:
Page 153 and 154:
Page 155 and 156:
Page 157 and 158:
7 Neurotoxicity: Toxic Responses of
Page 159 and 160:
ions moving out of the cell brings
Page 161 and 162:
an effect seen with some neurotoxic
Page 163 and 164:
7.4 INTERACTIONS OF INDUSTRIAL CHEM
Page 165 and 166:
• A study of the patient’s hist
Page 167 and 168:
• Although much of the damage whi
Page 169 and 170:
158 DERMAL AND OCULAR TOXICOLOGY Fi
Page 171 and 172:
160 DERMAL AND OCULAR TOXICOLOGY P4
Page 173 and 174:
162 DERMAL AND OCULAR TOXICOLOGY ca
Page 175 and 176:
164 DERMAL AND OCULAR TOXICOLOGY ke
Page 177 and 178:
166 DERMAL AND OCULAR TOXICOLOGY Fi
Page 179 and 180:
168 DERMAL AND OCULAR TOXICOLOGY
Page 181 and 182:
170 PULMONOTOXICITY: TOXIC EFFECTS
Page 183 and 184:
Page 185 and 186:
Page 187 and 188:
Page 189 and 190:
Page 191 and 192:
Page 193 and 194:
Page 195 and 196:
Page 197 and 198:
Page 199 and 200:
10 Immunotoxicity: Toxic Effects on
Page 201 and 202:
10.2 BIOLOGY OF THE IMMUNE RESPONSE
Page 203 and 204:
10.2 BIOLOGY OF THE IMMUNE RESPONSE
Page 205 and 206:
certain situations immunosuppressio
Page 207 and 208:
10.5 TESTS FOR DETECTING IMMUNOTOXI
Page 209 and 210:
10.6 SPECIFIC CHEMICALS THAT ADVERS
Page 211 and 212:
10.6 SPECIFIC CHEMICALS THAT ADVERS
Page 213 and 214:
animal origin have also been shown
Page 215 and 216:
The mainstay of treatment of multip
Page 217 and 218:
PART II Specific Areas of Concern P
Page 219 and 220:
210 REPRODUCTIVE TOXICOLOGY continu
Page 221 and 222:
212 REPRODUCTIVE TOXICOLOGY Underst
Page 223 and 224:
214 REPRODUCTIVE TOXICOLOGY spermat
Page 225 and 226:
216 REPRODUCTIVE TOXICOLOGY gonadot
Page 227 and 228:
218 REPRODUCTIVE TOXICOLOGY TABLE 1
Page 229 and 230:
Figure 11.3 Cycle of follicular dev
Page 231 and 232:
222 REPRODUCTIVE TOXICOLOGY Figure
Page 233 and 234:
224 REPRODUCTIVE TOXICOLOGY TABLE 1
Page 235 and 236:
226 Figure 11.5 Developmental tree
Page 237 and 238:
228 REPRODUCTIVE TOXICOLOGY is clea
Page 239 and 240:
230 REPRODUCTIVE TOXICOLOGY genital
Page 241 and 242:
232 REPRODUCTIVE TOXICOLOGY to occu
Page 243 and 244:
234 REPRODUCTIVE TOXICOLOGY these r
Page 245 and 246:
236 REPRODUCTIVE TOXICOLOGY Two imp
Page 247 and 248:
238 REPRODUCTIVE TOXICOLOGY Sundara
Page 249 and 250:
240 MUTAGENESIS AND GENETIC TOXICOL
Page 251 and 252:
Page 253 and 254:
Page 255 and 256:
Page 257 and 258:
248 Figure 12.5 Example of DNA addu
Page 259 and 260:
Page 261 and 262:
Page 263 and 264:
Page 265 and 266:
Page 267 and 268:
TABLE 12-3 NTP and Gene-Tox Evaluat
Page 269 and 270:
Page 271 and 272:
Page 273 and 274:
Page 275 and 276:
266 CHEMICAL CARCINOGENESIS 13.1 TH
Page 277 and 278:
268 CHEMICAL CARCINOGENESIS TABLE 1
Page 279 and 280:
270 CHEMICAL CARCINOGENESIS researc
Page 281 and 282:
272 CHEMICAL CARCINOGENESIS Figure
Page 283 and 284:
Page 285 and 286:
276
Page 287 and 288:
Page 289 and 290:
280 CHEMICAL CARCINOGENESIS 13.4 MO
Page 291 and 292:
Page 293 and 294:
Page 295 and 296:
286 CHEMICAL CARCINOGENESIS make a
Page 297 and 298:
288 Figure 13.8 A genetic model of
Page 299 and 300:
290 CHEMICAL CARCINOGENESIS Increas
Page 301 and 302:
292 CHEMICAL CARCINOGENESIS may be
Page 303 and 304:
294 CHEMICAL CARCINOGENESIS • The
Page 305 and 306:
296 CHEMICAL CARCINOGENESIS evaluat
Page 307 and 308:
298 CHEMICAL CARCINOGENESIS In rats
Page 309 and 310:
Page 311 and 312:
302 CHEMICAL CARCINOGENESIS with ex
Page 313 and 314:
Page 315 and 316:
Page 317 and 318:
Page 319 and 320:
Page 321 and 322:
Page 323 and 324:
Page 325 and 326:
316 CHEMICAL CARCINOGENESIS similar
Page 327 and 328:
Page 329 and 330:
Page 331 and 332:
Page 333 and 334:
324 CHEMICAL CARCINOGENESIS Knudson
Page 335 and 336:
326 PROPERTIES AND EFFECTS OF METAL
Page 337 and 338:
Page 339 and 340:
Page 341 and 342:
332 TABLE 14.2 Target Organ Toxicit
Page 343 and 344:
Page 345 and 346:
Page 347 and 348:
Page 349 and 350:
Page 351 and 352:
Page 353 and 354:
Page 355 and 356:
346 PROPERTIES AND EFFECTS OF PESTI
Page 357 and 358:
Page 359 and 360:
Page 361 and 362:
Page 363 and 364:
Page 365 and 366:
Page 367 and 368:
Page 369 and 370:
Page 371 and 372:
Page 373 and 374:
Page 375 and 376:
Page 377 and 378:
368 PROPERTIES AND EFFECTS OF ORGAN
Page 379 and 380:
370 TABLE 16.1 (Continued) Water So
Page 381 and 382:
Page 383 and 384:
Page 385 and 386:
Page 387 and 388:
Page 389 and 390:
Page 391 and 392:
Page 393 and 394:
Page 395 and 396:
Page 397 and 398:
Page 399 and 400:
Page 401 and 402:
Page 403 and 404:
Page 405 and 406:
Page 407 and 408:
Page 409 and 410:
Page 411 and 412:
Page 413 and 414:
Page 415 and 416:
Page 417 and 418:
Page 419 and 420:
410 PROPERTIES AND EFFECTS OF NATUR
Page 421 and 422:
Page 423 and 424:
Page 425 and 426:
Page 427 and 428: 418 PROPERTIES AND EFFECTS OF NATUR
Page 443 and 444: PART III Applications Principles of
Page 445 and 446: 438 RISK ASSESSMENT 18.1 RISK ASSES
Page 447 and 448: 440 RISK ASSESSMENT control populat
Page 449 and 450: 442 RISK ASSESSMENT there are some
Page 451 and 452: 444 RISK ASSESSMENT • It identifi
Page 453 and 454: 446 RISK ASSESSMENT chemical poses
Page 455 and 456: 448 RISK ASSESSMENT • Estimating
Page 457 and 458: 450 RISK ASSESSMENT Figure 18.3 Est
Page 459 and 460: 452 RISK ASSESSMENT • As discusse
Page 461 and 462: 454 RISK ASSESSMENT divided by a de
Page 463 and 464: 456 RISK ASSESSMENT Because low-dos
Page 465 and 466: 458 RISK ASSESSMENT TABLE 18.1 Expe
Page 467 and 468: 460 RISK ASSESSMENT leading to impo
Page 469 and 470: 462 RISK ASSESSMENT characterizatio
Page 471 and 472: 464 RISK ASSESSMENT Figure 18.7 Sim
Page 473 and 474: 466 RISK ASSESSMENT The RPF values
Page 475 and 476: 468 RISK ASSESSMENT producing the e
Page 477: 470 RISK ASSESSMENT TABLE 18.4b Can
Page 481 and 482: 474 RISK ASSESSMENT A second reason
Page 483 and 484: 476 RISK ASSESSMENT Barnard, R. C.,
Page 485 and 486: 19 Example of Risk Assessment Appli
Page 487 and 488: 19.3 LEAD EXPOSURE AND WOMEN OF CHI
Page 489 and 490: 19.4 PETROLEUM HYDROCARBONS: ASSESS
Page 491 and 492: 19.4 PETROLEUM HYDROCARBONS: ASSESS
Page 493 and 494: 19.5 RISK ASSESSMENT FOR ARSENIC 48
Page 495 and 496: 19.5 RISK ASSESSMENT FOR ARSENIC 48
Page 497 and 498: 19.6 REEVALUATION OF THE CARCINOGEN
Page 503 and 504: REFERENCES AND SUGGESTED READING RE
Page 505 and 506: 20 Occupational and Environmental H
Page 507 and 508: 20.1 DEFINITION AND SCOPE OF THE PR
Page 509 and 510: 20.4 HUMAN RESOURCES IMPORTANT TO O
Page 511 and 512: treatment, or medical removal from
Page 513 and 514: Academic practices welcome complica
Page 515 and 516: Occupational and environmental medi
Page 517 and 518: 512 EPIDEMIOLOGIC ISSUES IN OCCUPAT
Page 527 and 528: 22 Controlling Occupational and Env
Page 529 and 530:
22.2 EXPOSURE LIMITS 525 The TLVs
Page 531 and 532:
modified “reference doses” to r
Page 533 and 534:
observation process, followed by re
Page 535 and 536:
• Hazard-specific training to ens
Page 537 and 538:
22.3 PROGRAM MANAGEMENT 533 Conside
Page 539 and 540:
Figure 22.1 22.3 PROGRAM MANAGEMENT
Page 541 and 542:
fundamental viability of the work p
Page 543 and 544:
Figure 22.2. 22.3 PROGRAM MANAGEMEN
Page 545 and 546:
• Physical assessment and fit tes
Page 547 and 548:
The study was designed to minimize
Page 549 and 550:
TABLE 22.3 Margins of Safety at For
Page 551 and 552:
top, and numerous slots with smalle
Page 553 and 554:
TABLE 22.5 Comparison of Time-Weigh
Page 555 and 556:
• Housing or building code violat
Page 557 and 558:
• Environmental exposure limits,
Page 559 and 560:
GLOSSARY Glossary absorption The mo
Page 561 and 562:
GLOSSARY 557 antipyretic An agent t
Page 563 and 564:
GLOSSARY 559 chloracne An acne-like
Page 565 and 566:
GLOSSARY 561 eczema A superficial i
Page 567 and 568:
GLOSSARY 563 hemolytic anemia Anemi
Page 569 and 570:
GLOSSARY 565 lipoprotein Any of a g
Page 571 and 572:
GLOSSARY 567 necrosis Death of one
Page 573 and 574:
pernicious anemia The progressive,
Page 575 and 576:
GLOSSARY 571 cells have both endoth
Page 577 and 578:
GLOSSARY 573 tolerance The ability
Page 579 and 580:
576 INDEX Allergic reaction (contin
Page 581 and 582:
578 INDEX Biotransformation (contin
Page 583 and 584:
580 INDEX Children’s health statu
Page 585 and 586:
582 INDEX Diet and nutrition (conti
Page 587 and 588:
584 INDEX Estrogens: endocrine disr
Page 589 and 590:
586 INDEX Hair, toxic agent excreti
Page 591 and 592:
588 INDEX hnmunoglobulins: autoimmu
Page 593 and 594:
590 INDEX Loop of Henle, structure
Page 595 and 596:
592 INDEX Mixed exposure patterns,
Page 597 and 598:
594 INDEX Nutritional deficiencies,
Page 599 and 600:
596 INDEX Pesticides (continued) Pe
Page 601 and 602:
598 INDEX Relative potency factor (
Page 603 and 604:
600 INDEX Solvents (continued) phys
Page 605 and 606:
602 INDEX Tumorigenesis (continued)
show all

PRINCIPLES OF TOXICOLOGY

Create successful ePaper yourself

Delete template?

Save as template?