Index

Note: Page numbers with “f” and “t” denote figures and tables, respectively.

A volume or mass distribution of in brain, II:1034

AAS. See Atomic absorption particles, I:50f of Cd, II:680
spectrometry metabolism Acetates, I:19
Abortions, I:412 of As, II:587 ACGIH. See American Conference
Absolute occurrence, I:268 of Al, II:551–553, II:552t of Governmental Industrial
Absorption, I:49, I:513, II:919–920, of Sb, II:569–572 Hygienists
II:1023–1024 of Mn, II:982–984 Acid rain, I:12–13, I:426
of Ag, II:1211 of Mo, II:1079–1080 Acidosis, metabolic, II:897
of Al, II:551–553, II:552t of Ni, II:1096–1097 Acid-volatile sulfide (AVS), I:434
alveolar, I:50, I:51t of Pd, II:1117 ACSL. See Advanced Continuous
of Ba, II:627–628 prevention of, I:69–70 Simulation Language
of Be, II:639–640 of Pb, II:919–921 Activator protein 1 (AF-1), I:434
of Bi, II:657–658 of Pt, II:1129–1132 ADI. See Acceptable daily intakes
behavior, I:83 of Se, II:1184–1185 Adrenergic compounds, I:54
of Cd, II:674–676 signal generation principal, I:83 Advanced Continuous Simulation
of Co through skin, I:49, II:588, Language (ACSL), I:67–68
by animals, II:747–748 II:1094–1095 Adverse Outcome Pathways (AOP),
by humans, II:748 of Sn I:468
of Cr, II:720. See also Uptakes inorganic, II:1255–1258 AE. See Allowable exposure level
of Cu, II:768–769 organic, II:1258–1263 Aerosols, I:46
of Fe, II:886–887, II:887f of Te, II:1219–1220 condensation, I:48
of gases, I:51 of Ti, II:1290 disintegration, I:48
of Ga, II:789–790 of Tl, II:1231–1232 metal-containing, I:48–50, I:50f
of Ge, II:804–805 total absorption, I:58, I:58f AES. See Atomic emission
of Hg, inorganic, II:1023–1024, of U, II:1318–1320 spectrometry
II:1034 of vapors, I:51 AF-1. See Activator protein 1
of Hg, organic, II:1045 of V, II:1351–1352 Affinity chromatography (AC), I:27–28
of In, II:847 of W, II:1300 AFS. See Atomic fluorescence
after ingestion, I:56 of Zn, II:1376–1377 spectrometry
foodstuffs, I:56 AC. See Affinity chromatography Ag. See Silver
gastrointestinal absorption, I:57 Academic skills, I:306 Age, I:214–216, I:218
gastrointestinal route, I:56 Acceptable daily intakes (ADI), I:285 Agency for Toxic Substances and
inorganic salts of metals, I:57 Acceptable range of oral intakes Disease Registry (ATSDR),
methyl mercury, I:56 (AROI), I:281 I:142
oral dose of metal salt, I:57 definitions of, I:283–285, I:284f Air, I:46–47, II:913, II:1030, II:1371
paracellular migration, I:57 genetically determined, I:284 Ag and, II:1210
respiratory tract clearance, nongenetically determined, ambient, I:24, II:789, II:803–804
I:57–58 I:284–285 In and, II:847
ingestion/inhalation/toxicokinetics, design of, I:282–283 Bi and, II:657
of V, II:1351–1354 determination of, I:291–292, I:291f Cd and, II:673
after inhalation, I:49 estimation of, I:290–292 Co and, II:745–746
clearance of particles, I:52–56 Accumulation, I:287 Cr and, II:719
deposition of particles, I:51–52 bioavailability/elimination/ Cu and, II:767
gases and vapors, I:51 uptakes, ecotoxicology of Hg and, II:1021
MMAD, I:50 metals and, I:287 Mn on, II:979–980

i1
i2 Index

Air (Continued ) restrictive pulmonary disease as, dose-response relationships/effects

Pd and, II:1115–1116
Se and, II:1178
As and, II:586
Ba and, II:626–627
Be and, II:637–638
contaminated, I:10
industrial, I:25
iridium levels in, II:860–862
lanthanum environmental levels,
II:905–906
Mo and, II:1079
Ni and, II:1093–1094
sampling/sample preparation of,
I:25, I:514
Sb and, II:568–569
Sn and, II:1253–1255
Te and, II:1219
Ti and, II:1289
transport of metals into, I:426–427
U and, II:1316–1317
V in, II:1350
workplace, I:167–168
Akt, I:185
Al. See Aluminum
ALAD. See δ-aminolevulinic acid
dehydrase
Albumin, I:165t, I:335–336
Alcohol, I:342
CNS and, I:215
ethyl, I:215
Hg and, I:215
metal toxicology and, I:215
Alkaline, batteries, I:6–7
Alkaline phosphatase, II:1224
Alkylmercury, II:1019, II:1054–1055,
II:1063
Allergies, II:560
Allowable exposure level (AE), I:231
Alpha-1-microglobulin, I:164, II:687,
II:701–702
Aluminum (Al), I:10, I:12–13
analytical methods/problems
associated with, II:550
carcinogenicity of, II:560
chemical/physical properties of
compounds, II:549–550
dietary exposure to, II:551, II:552f
effects of
allergic, II:560
on bone, II:559–560
carcinogenic, II:560–561
on CNS, II:557–559
gastrointestinal, II:554–555
on hematopoietic tissues, II:560
ischemicheart disease as, II:560
neurobehavioral, II:557–559
obstructive pulmonary disease
as, II:556–557
II:555–556
on skin, II:560
environmental exposure/levels of,
II:551, II:552f
fluoride, II:556
grinding/polishing of, II:555
guidelinesfor, II:561–562, II:561t
kinetics of
absorption, II:551–553, II:552t
biological monitoring, II:552t,
II:553–554, II:554f
distribution and, II:553
excretion and, II:553
medical, II:557
neonatal exposure/developmental
effects from, I:417–418
occupational, II:557–559
occupational exposure to, II:551,
II:552f
prenatal exposure/developmental
effects of, I:414–417
production/use of, II:550–551
salts, II:551
sulfate solution, II:554–556
Alveolar absorption, I:50, I:51t
Alzheimer’s disease (AD), II:559
American Conference of
Governmental Industrial
Hygienists (ACGIH), I:471,
II:576, II:647
Ames test, II:1276
Amino acids, I:431
δ-aminolevulinic acid dehydrase
(ALAD), I:22, I:250–252,
II:922
effect modification of, I:250
genotypes, I:250
studies on, I:250
δ-aminolevulinic acid dehydratase
(ALADH), I:273, I:447,
II:922–923
inhibition of, I:233–234
Ammonium chloride, I:62, I:62f
Ammonium pyrrolidine dithiocar-
bamate (APDC), I:33, I:36
Animal(s), II:1100–1101, II:1103,
II:1266–1268, II:1351–1352
Ba and, II:627
Be and, II:638, II:643, II:645,
II:647–648
biological half-time of Sb and,
II:571–572
Co and
absorption/inhalation of,
II:747–748
digestion of, II:748
distribution/excretion of,
II:748–749
of, II:1212–1213
of Te, II:1221–1224
Sb and
circulatory system of, II:573
dose-response relationships’
effects of, II:573
endocrine system of, II:573
liver/kidney of, II:574
Tl and, II:1234
W and, dose-response relation-
ships/effects of, II:1301–1304
Anodic stripping voltammetry
(ASV), II:912
Antacids, II:551
Antarctic, I:443
Antibody
forming cell, II:791
mediated reactions (Type I
hypersensitivity), I:383
Antimony (Sb), I:7, I:441
analytical methods/problems
associated with, II:565–566
animals and, dose-response
relationships/effects of, II:573
biological half-time of
animals and, II:571–572
humans and, II:572
biological monitoring of, II:572–573
carcinogenicity of, II:576
chemical/physical properties of,
II:565
effects on animals’
circulatory system, II:573–574
endocrine system, II:574
liver/kidney, II:573–574
effects on humans’
gastrointestinal tract, II:574
immunology, II:575
respiratory system, II:574–575,
II:575f
skin, II:575
environmental exposures/levels of
in air/soil/water, II:568–569
in cigarettes, II:569
in daily intake/food, II:567–568
in working environment, II:569
genotoxic effects of, II:576
humans and, dose-response relation-
ships/effects of, II:574–575
metabolism of
absorption, II:569
distribution, II:570–571
excretion, II:571
ingestion and, II:570
inhalation and, II:569
production/uses of, II:566–567
Antineoplastic compounds, II:794
AOP. See Adverse Outcome Pathways

APDC. See Ammonium pyrrolidine
dithiocarbamate
Aquatic food chains, I:431
Aquatic systems, I:519
Arctic, I:443
Area under the plasma metal
concentration curve (AUC),
I:160–161
Argentina, II:599, II:611
AROI. See Acceptable range of oral
intakes
Arsenate, I:26–27, I:174, I:187
Arsenic (As), I:144–145, I:218, I:441f,
I:442
acid, II:582
analytical methods/problems
associated with, II:582–583
arsine and, II:614–616
As compounds, genotoxic/
mutagenic effects of, I:180
biological monitoring of
in blood, II:596–597
in hair, II:597–598
in organs, II:595–596, II:595t
carcinogenicity of, I:8–9, I:173,
II:593–594, II:604–609, II:604t,
II:608t
animal models in, I:359–360
epidemiological observations of,
I:358–359
evaluation of, I:360–361
in vitro studies for, I:360
chemical/physical properties of,
II:582
diagnosis/prognosis/treatments
for
acute poisoning, II:613–614
chronic poisoning, II:614
dose-effect/dose-response relation-
ships of, II:610–613
effects of
acute/subacute, II:598, II:598t
carcinogenic, II:604–609, II:604t,
II:608t
chronic cardiovascular, I:5,
II:601–604, II:602t
dermal, II:599, II:599t
developmental/reproductive,
II:609
gastrointestinal, II:599
genotoxic, II:609–610
hematological, II:600
hepatic, II:600
immunologic, II:601
gold mining, II:832
lethal, II:598
metabolic, II:600–601
mutagenic, II:609–610
neural, II:599–600
Index
noncardiovascular, II:598–601,
II:598t
ophthalmic, II:601
respiratory, II:600
environmental exposure/levels of
air and, II:586–587
daily intake/food and,
II:584–585
soil and, II:586
tobacco and, II:587
water and, II:585–586
inorganic, I:5, I:26–27
interactions between, other
compounds and, II:610
metabolism of, I:242–247
absorption, II:610
biological half-time, II:591
biotransformation, II:589–590
distribution/transport,
II:588–589
excretion, II:590–591
ingestion, II:588
toxicity, II:591–595
metal toxicity of, I:242–247
in metal-metal carcinogenic
interactions, I:224
metal-metal interactions and,
I:218
mutagenic effects of, I:371
neonatal exposure/developmental
effects from, I:417–418
occurrence of, I:7, I:10
prenatal exposure/developmental
effects of, I:414–417
production/uses of, II:583–584
Arsenic trioxide (As2O3), II:597
Arsenite (AsIII), I:26–27, I:187
cell signaling pathways and, I:187
metal toxicity of, I:175
Arsenobetaine (AsB), I:26, I:33
Arsenocholine (AsC), I:33
Arsenosugars, I:26–27
Arsine, I:30, II:614–616
As. See Arsenic
As2O3. See Arsenic trioxide
AsA. See Ascorbic acid
AsB. See Arsenobetaine
AsC. See Arsenocholine
Ascorbate, I:20
Ascorbic acid (AsA), I:224–225
Asia, I:535
AsIII. See Arsenite
Asphalt, I:230
Astrocytes, II:1052–1053
ASV. See Anodic stripping
voltammetry
ATSDR. See Agency for Toxic
Substances and Disease
Registry
i3
Atmosphere, II:1370
Atomic absorption spectrometry
(AAS), I:32–33, II:912
atomization methods for, I:32–33
flame, I:32–33
Atomic emission spectrometry
(AES), I:33–34
Atomic fluorescence spectrometry
(AFS), I:32–33
Attributable risk, I:267
Au. See Gold
AUC. See Area under the plasma
metal concentration curve
Australia, II:1312–1313
Autoimmune diseases
by Cd, I:392–393
by Hg, I:393
by Pb, I:393
Autoimmunity, immunotoxicology
of metals and, I:391–392
xenobiotics and, I:392–393
AVS. See Acid-volatile sulfide
B
Ba. See Barium
Bacillus subtilis, II:610
BAL (2,3-dimercaptopropanol),
I:18–19
Bangladesh, I:10, II:585–586, II:599
Barium (Ba)
analytical methods/problems
associated with, II:626
biological monitoring of, II:629
chemical/physical properties of,
II:625–626
dietary intake of, II:627
dose-response relationships/effects
of, II:629–632
environmental exposures/levels of
air/soil/water and, II:626–627
animals/plants and, II:627
kinetics of
distribution/transport, II:628
excretion, II:628–629
ingestion and, II:628
inhalation and, II:627
production/uses of, II:626
treatments for, II:632–633
Batteries, alkaline, I:6–7
Bauxite, II:550
BBB. See Blood-brain barrier (BBB)
Be. See Beryllium
BE. See Biomonitoring equivalents
Behavior Rating Inventory of
Executive Function (BRIEF),
I:306
BeLPT. See Beryllium lymphocyte
proliferation test
i4 Index

Benchmark dose (BMD), I:210–211, Bioavailability, I:287, I:430–431 results’ interpretation of, I:164
I:274 Biological basis, for modeling, speciation in, I:163
assessment of, I:275–276 I:207–208, I:208t biomarkers of susceptibility in,
methylmercury exposure, I:276t Biological fluids, II:1132–1133 II:650
population dose, I:274 Biological functions, II:1180–1181 of Cd
structural equation models, I:276–277 Biological half-time/half-life, II:806, biomarkers of effects and,
Benchmark dose level (BMDL), II:1024–1025 I:156–157, II:685, II:689t
I:206–207, I:211 of Ag, II:1211–1212 biomarkers of exposure and,
Benchmark response (BMR), of As, II:591 II:681–685, II:684f, II:685t
I:210–211, I:275–276 of Au, II:824 of Cr
Berylliosis, II:636 of Ba, II:627 biomarkers of effects and,
Beryllium (Be), I:58–59 of Bi, II:659 II:707–708
analytical methods/problems of Cd, I:11–12, I:680 biomarkers of exposure and,
associated with, II:636 of Co, II:747, II:749 II:707
animals and, II:642–643, II:645 of Cr, II:722 of Cu, II:775–776
carcinogenicity of, I:8–9, I:364–365, of Cu, II:774 ecotoxicology of metals and,
II:646–648 excretion of metals and, I:440–455
chemical/physical properties of, I:62–63 ethical considerations for, I:167
II:636 of Ga, II:790 future trends in, I:169
dose-response relationships/effects of Ge, II:806 of inorganic Pb, II:927–933,
of, II:641 of Hg, II:1024–1025 II:930f–931f, II:932t
biomarkers of effect and, of In, II:848 introduction to, I:155–158, I:157f
II:649–650 of inorganic Sn, II:1257 metabolism of Al and, II:552t,
biomarkers of susceptibility and, of Mn, II:975–976 II:554, II:554f
II:650 of Mo, II:1080–1081 metals and, toxicology of, I:11
dermal, II:641–642 of Ni, II:1097–1098 in occupational risk assessment,
genotoxic, II:648 of Pb, II:921f I:167–168
systemic, II:645–646 of Sb of organic Pb, II:954–955
toxic action mechanisms and, animals and, II:592 Pt and, II:1133
II:648–649 humans and, II:593 QA reference materials for,
endocrine effects of, II:646 of Se, II:1188–1189 I:158–159
environmental exposure/levels of of Te, II:1220 reference values for, I:161–162
air/soil/water and, II:637–638 of Ti, II:1291 results, I:159
animals/dietary intake/plants of Tl, II:1233 of Sb, II:572–573
and, II:638 of U, II:1322 of Se, II:1189
daily, II:638 of V, II:1353–1354 biomarkers of effects and,
working, II:638–639 of W, II:1301 II:1189–1190
hematological effects of, II:646 of Zn, II:1369 biomarkers of exposure and,
hypersensitivity and, I:384 Biological monitoring (BM), I:142, II:1189
kinetics of I:515 specimen/urine sample standardi-
absorption/ingestion/inhalation of As zation and, I:159
and, II:639–640 in blood, II:596–597 blood as, I:160–161
distribution/excretion/transport in hair, II:597–598 of Te, II:1220–1221
and, II:640–641 in organs, II:595–596, II:595t of Tl, II:1233–1234
metal toxicology and, I:247–248 analytical/preanalytical sources of of V, II:1354–1355
production/uses of, II:636–637 error in, I:158 of W, II:1301
Beryllium lymphocyte proliferation of Ba, II:629 Biomarker(s), I:46
test (BeLPT), II:643 biomarkers of effects in, I:156, of critical effect, I:288, I:290
Beta-2-microglobulin, I:156–157, II:649–650 early, I:156–157
I:164, I:273, I:316, II:677, II:873, genotoxicity, I:166 of deficiency, I:289–290
II:890, II:1323, II:1332 for lead, I:157 definition of, I:156
Bi. See Bismuth lung toxicity, I:165–166 of effects, I:156
Bicarbonate anions, I:62, I:62f neurotoxicity, I:165 Be and, II:649–650
Bile, I:60, II:776 other target organs and, I:166 Cd and, I:156–157, II:685, II:685t
Biliary excretion, I:497 renal toxicity, I:164–165, I:165t Cr and, II:737–738
Binary weight-of-evidence method biomarkers of exposure in, I:156, genotoxicity, I:166
(BINWOE), I:232–233, I:233t II:927–930 for lead, I:157
BINWOE. See Binary weight-of analytical approach to, I:163 lung toxicity, I:165–166
evidence method kinetics/sampling of, I:163–164 neurotoxicity, I:165

other target organs and, I:166
renal toxicity, I:164–165, I:165t
Se and, II:1189–1190
of exposure, I:156, II:927
analytical approach to, II:915–916
challenges related to use of,
I:164
Cd and, II:681–685, II:684f,
II:685t
Cr and, II:737
kinetics/sampling of, I:163–164
Se and, II:1189
speciation in, II:1180
U and, II:1335–1336, II:1336t
as HI, I:438–439
of internal dose, exposure, I:156
of susceptibility, I:156, I:157f
Be and, II:650
of target dose, I:158, I:464
uses of, I:464
Biomonitoring equivalents (BEs), I:143
Biosensors, for monitoring metal
ions, I:36
Biotic ligand-modeling concept
(BLM), I:434
Biotransformation, I:58–60, II:924,
II:1047, II:1257–1258,
II:1262–1263, II:1371
metabolism, of As, II:589–590
of metals, I:58–60, I:59f
of Se, II:1186–1187
Birds, I:5, I:450
Bismethylmercury selenide, II:1060
Bismuth (Bi), I:12–13
analytical methods/problems,
II:655–656
associated with, II:655–656
biological monitoring of, II:659
chemical/physical properties of,
II:655
dose-response relationships/
effects of
animals, II:659–662
humans, II:659–660, II:662–663
environmental exposure/levels of
ambient air/rocks/soil/water
and, II:657
cosmetics/pharmaceuticals and,
II:657
food and, II:657
metabolism of
absorption, II:657–658
biological half-time, II:659
distribution/excretion, II:658
production/uses of, II:656–657,
II:656f
treatments for, II:663
Blackfoot disease, II:602, II:611
Blank measures, I:40
Index
BLM. See Biotic ligand-modeling
concept
Blood, II:572, II:596–597, II:754,
II:1031–1033, II:1376
analysis, II:912–913
blood-forming organs, II:939–940
distribution of, II:921–923, II:922f
lead, II:927–929
levels, MeHg in, I:11
loss, I:273–274
pressure, II:942–943
specimen/urine sample standardi-
zation and, I:160–161
trace elements in, I:24
uses of, I:46
Blood-brain barrier (BBB),
I:300–301
Blum-Druckrey model, I:208
BM. See Biological monitoring
BMD. See Benchmark dose
BMDL. See Benchmark dose level
BMR. See Benchmark response
Bone, II:559–560
Brain, I:491, II:771, II:1046–1047
accumulation in, II:1053
fetal, II:1034
BRIEF. See Behavior Rating
Inventory of Executive
Function (BRIEF)
Bromides, I:19
Bromosulfophthalein, I:60–61
Bronchial tree, II:751–752
2-butoxyethanol, I:225
C oxide, I:53
Ca(NO3)2. See Nitrates
Cadmium (Cd), I:58–59, I:145. See also
Itai-Itai disease
accumulation, II:680–681
analytical methods/problems
associated with, II:668–669
biological half-time of, I:11–12
biological monitoring of
biomarkers of effects and, I:157,
II:685, II:685t
biomarkers of exposure and,
II:681–685, II:685t
data, I:145–148
carcinogenicity of, I:8–9, II:696–698
animal models in, I:363
epidemiological observations of,
I:361–362
evaluation of, I:363–364
in vitro studies, I:363
cell signaling pathways and,
I:188–189
chemical/physical properties of,
II:668
i5
compounds, genotoxic/mutagenic
effects of, I:180
diagnosis/prognosis/prevention/
treatments for, II:707–708
dose-response relationships/effects
of, II:701–704, II:702f
acute poisoning and, II:686
chronic poisoning and,
II:686–693, II:689t, II:691f
ecotoxicology of
background levels/emissions
and, I:442–443
contamination and, I:443
organism uptakes and, I:443
environmental exposure/levels of
ambient air and, II:673
daily intake/food and, I:25–26,
II:670–672, II:671t
soil/water and, II:672–673
tobacco and, II:673
working, II:673–674, II:674t
epigenetics of, I:183
intake rates, I:148, I:148t
levels in Japan, I:162
metabolism of, I:11–12
metal toxicology and, I:248–249
metallothionein and cadmium,
II:676
metal-metal interactions and,
I:219–221, I:220f
multicompartment model for,
I:67–68, I:67f–68f
mutagenic effects of, I:371–372
neurotoxic effects of, I:438
occurrence of, I:6–7
prenatal exposure/developmental
effects of, I:412
production/uses of, II:669–670,
II:669f, II:670t
sensitive subpopulations, I:148
in soil, I:11
in tobacco smoke, I:11
toxicokinetics of
absorption/ingestion/
inhalation, II:674–676
biological half-life and, II:678f,
II:680
distribution/transport and,
II:676–679, II:676f, II:678f–679f
xenobiotics/autoimmune diseases
by, I:393
Calcium, I:220
channels, as toxic metal, I:175
essential metals and, I:175
Calcium disodium edetate (calcium
EDTA), I:500–501
Calcium EDTA. See Calcium
disodium edetate
i6
Canada, II:1308
Cancer(s), II:946, II:1328–1329
bladder, II:612
breast, I:274
development of, I:225
epigeneticity of metals in,
I:181–182
internal, II:607–608, II:608t
liver, II:607, II:608t
lung, I:274, II:604t, II:605–606
reproduction and, II:952
respiratory, II:612
risk assessments, I:209
short, characteristic, I:274
skin, I:5, II:604t, II:605
species-to-species extrapolations
and, I:208–209
studies, II:609–610
urothelial, II:606–607
Capillary electrophoresis (CE), I:27,
I:30
Capillary isoelectric focusing (CIEF),
I:30
Capillary zone electrophoresis
(CZE), I:30
Carbohydrates, I:431
Carbonic anhydrase, I:22, I:431
Carboxypeptidase, I:22
Carcinogenicity, II:812, II:1103–1105,
II:1120, II:1359–1360
of Al, II:560–561
of As, I:8–9, II:595, II:604–609,
II:604t, II:608t
animal models in, I:359–360
epidemiological observations of,
I:358–359
evaluation of, I:360–361
in vitro studies, I:360
of Be, I:8–9, I:364–365, II:646–648
of Cd, I:8–9, II:696–698
animal models in, I:363
epidemiological observations of,
I:361–362
evaluation of, I:363–364
in vitro studies, I:363
of Co, I:368, II:758–759
of Cr, I:8–9, II:738
animal models in, I:356–357
epidemiological observations of,
I:355–356
evaluation of, I:357–358
in vitro studies, I:357
of Cu, II:778
of metal compounds, I:9
As and, I:358–359
beryllium and, I:8–9, I:364–365,
II:646–648
Cd and, I:361–362
Co and, I:368
Index
Cr and, I:355–356
Fe and, I:363–364, I:368–369
lead and, I:366–367
Mg and, I:369
mutagenic effects of, I:179
Ni and, I:352–353
principal, I:351–370
Pt and, I:369–370
Ti and, I:370, II:1294
of metals, I:8–9, I:173
of Mn, I:369
of Ni, I:8–9
animal models in, I:353–354
epidemiological observations of,
I:352–353
evaluation of, I:354–355
of Pb, I:8–9, I:366
animal models in, I:367
epidemiological observations of,
I:366–367
evaluation of, I:367–368
of Sb, II:576
of Se, II:1197–1198
of Ti, I:370
animals and, II:1294
humans and, II:1294
Cardiac effects, II:602
Cardiomyopathy, II:754–755
Cardiovascular disease (CVD), I:313
introduction, I:313–314
metals relations with, I:314
aluminum, I:314
arsenic, I:314–315
beryllium, I:315–316
cadmium, I:316–318
chromium, I:318–319
cobalt, I:319–320
iron, I:320–321
lead, I:321
magnesium, I:321–323
manganese, I:323–324
mercury, I:324–325
nickel, I:325–326
selenium, I:326–327
uranium, I:327
zinc, I:327–328
Cardiovascular disorders, I:5
As/chronic, I:5, II:601–604, II:602t
Cardiovascular effects, II:645–646,
II:1359
Cardiovascular system, I:7, I:490,
II:942–944, II:996–997
Carotid atherosclerosis, II:603–604
Catalase, I:184–185
CBD. See Chronic beryllium disease
CCA. See Chromated copper arsenate
Cd. See Cadmium
CDC. See U.S. Centers for Disease
Control and Prevention
CE. See Capillary electrophoresis
CELF-4. See Clinical Evaluation of
Language Fundamentals-
Fourth Edition (CELF-4)
Cell(s)
concentrations of metal, I:6
culture, human, II:1304
death, II:594
jurkat, I:189
mediated reactions (Type IV hyper-
sensitivity), I:383–384
protein, Clara, I:166
signaling pathways, II:594
As and, I:182–183
AF-1 and, I:186–187
Cd and, I:188–189
Co and, I:189–190
Cr and, I:189
HIF-1 and, I:185–186
introduction to, I:180–181
MAPK and, I:185
NF-AT and, I:186
NF-κB and, I:186
Ni and, I:190–191
other metals and, I:191
P13K/Akt and, I:185
ROS and, I:184–185
signal transduction pathways
and, I:184–187
Cellulose, I:25
Central nervous system (CNS), I:7,
I:490, II:933–938
Al’s effects on, II:557
development, I:301–303
academic skills, I:306
attention, I:305
clinical effects and early signs,
I:304–305
executive functions, I:306
human neurodevelopment, I:302f
infant neurodevelopment, I:305
IQ, I:305
language, I:305
learning and memory, I:305
motor skills, I:306
neonatal behavior, I:305
visuospatial skills, I:305
mercury in, I:489
methylmercury in, I:12, I:65–66,
I:65f
Ceratophyllum demersum, I:443
Cerebral spinal fluid (CSF), I:300–301
Certified reference materials
(CRMs), I:38
Ceruloplasmin, I:31, I:215
Cesium (Cs), I:454
(CH3)2C(SH)CH(NH2)CO2H. See
D-penicillamine
CH3. See Methyl

Chalcocite (Cu2S), II:766
Chalcopyrite (CuFeS2), II:766
Chelation
indications of, I:498
by molecules, I:433
therapy, I:498–503
Chemical bonds
covalent, I:17
ionic, I:17
Chemistry
bioinorganic, I:16
metal, I:21–22, I:21t
Chemotherapy, I:258–259
Children, I:517–518, I:536–537
exposure to metals and, I:49, I:216
lead and, I:221, II:954
paint and, II:919
metal poisoning and, I:517–518
Chile, II:599, II:611, II:766
China, I:220–221, I:224, II:599
Chlorides (NaCl), I:17–18
Cholinergic compounds, I:54
Chromate
oxyanion, I:59
as toxic metal, I:174
Chromated copper arsenate (CCA),
II:586
Chromium (Cr), I:318–319, I:445
biological monitoring of
biomarkers of effects and,
II:737–738
biomarkers of exposure and, II:737
carcinogenicity of, I:8–9, II:738–739
animal models in, I:356–357
epidemiological observations of,
I:355–356
evaluation of, I:357–358
in vitro studies, I:357
cell signaling pathways and, I:189
chemical analysis of, II:718
chemical/physical properties of,
II:717–718
compounds, genotoxic/mutagenic
effects of, I:179–180
concentrations of
ambient air/water, II:719
daily intake, II:719–720
food, II:719
soil, II:719
tobacco, II:719
DNA, II:718
dose/outcome effects of, II:722–737
environmental exposure/levels
of female reproduction and,
I:318–319
hexavalent, I:59f, I:60
hypersensitivity and, I:385
manufacture/uses of, II:718–719
metabolism/uptake of, II:720–722
Index
mutagenic effects of, I:179–180
prenatal exposure/developmental
effects of, I:318–319
prevention of, II:739
toxicity of, II:738
work-related exposure to, II:720
Chronic beryllium disease (CBD),
I:7, I:247–248, II:643
CIEF. See Capillary isoelectric
focusing
Circulation, II:311
Circulatory systems, II:573
Cirrhosis, II:773
Cisplatin, I:258–259
C-jun N terminal kinase (JNK), I:184,
I:188
Clara cell protein, I:166
Clearance of particles, I:52–53
particle translocation, I:55–56
peripheral lung clearance, I:54–55
tracheobronchial clearance, I:53–54
Clinical Evaluation of Language
Fundamentals-Fourth Edition
(CELF-4), I:305
CNS. See Central nervous system
Co. See Cobalt
Coal, I:47, II:1350
Cobalamins, I:22
Cobalt (Co), I:8–9, I:445
analytical methods associated with,
II:744
biological monitoring of, II:749–750
carcinogenicity, I:368
cell signaling pathways and,
I:189–190
chemical/physical properties of,
II:743–744, II:744f, II:744t
compounds, I:8–9
dose-response relationships/effects
of
carcinogenic, II:758–759
local, II:750–751
mutagenic, II:756–758
reprotoxicity and, II:759
respiratory, II:751–753
systemic, II:754–756
environmental exposure/levels of
ambient air/soil/water and,
II:745–746
daily intake/food and, II:745
occupational, II:746
hypersensitivity and, I:385
kineticsof
animals’ absorption/inhalation
and, II:747–748
animals’ distribution/excretion
and, II:748–749
humans’ absorption/digestion/
inhalation and, II:748
i7
humans’ distribution/excretion
and, II:748–749
metal toxicology and, I:249–250
as metal-containing biological
molecules, I:22
production/uses of, II:745
Coefficient of variation (CV), I:271
Cold vapor atomic absorption
spectrometry (CV-AAS), I:33
Concentration(s), I:40, II:557–558
of Cr
ambient air/water, II:719
daily intake, II:719–720
food, II:719
soil, II:719
tobacco, II:719
of critical organs/targets, dose,
I:464
emissions/uses, of Hg, I:448
in exposure to metals, uses of
critical organ, I:69–70, I:70f
of metal cells, I:6
Mn, II:1000–1002
population critical, I:216
of salts, I:441
of Zn, I:219
Condensation aerosols, I:48
Congo, Republic of, II:766
Contamination, importance of,
I:158
Control population, I:266
Copper (Cu), I:347, I:445–446, II:1086,
II:1377t
analytical methods/problems
associated with, II:766
biological interactions of, II:
778–779
biomarkers of exposure, II:776
in blood, urine, and other biological
fluids, II:775–776
carcinogenicity/mutagenicity/
teratogenic effects of, II:780
chemical/physical properties of,
II:765–766
deficiency, I:289, I:292
dose-response relationships/
systemic effects of, II:776–781
environmental exposure/levels of
ambient air/soil/water and,
II:767
daily intake/food and, II:766–767
working, II:767–768
essential metals and, I:177
levels, II:774–776
metabolism of, II:768, II:771–773
absorption/ingestion, II:768–769
biological half-time, II:774
distribution, II:769–771
excretion, II:773–774
i8 Index
Copper (Cu) (Continued ) of Te, II:1219
metalloenzymes, I:22 of Ti, II:1289
molybdenum-Zn metal-metal of U, II:1315
interactions, I:223 of V, II:1350–1351
prevention/treatments for, II:781–782 Dairy products, II:1374
production/uses of, II:766 Daphnia magna, I:436–437
tissue concentrations, II:774–775 Declaration of Brescia on Prevention
Cosmetics, II:657 of Neurotoxicity of Metals,
Coughing, I:53 I:526–528
Cr. See Chromium Decontamination, I:495
Crangon crangon, I:450 DEDTC. See Diethydithiocarbamate
Creatinine, I:335 Deferiprone (L1), I:502
Critical concentration, I:473–475 Deficiency
Critical effect, I:472–473 biomarkers of, I:289–290
Critical endpoint. See Critical effect clinical disease, I:289
Critical organ, I:6, I:472–473 Cu, I:289, I:293
CRMs. See Certified reference Fe, II:888–889
materials lethal, I:289
Cs. See Cesium risks associated with Ems
CSF. See Cerebral spinal fluid (CSF) basic concepts in, I:283–286,
C-TAD. See C-terminal activation I:284f
domain conclusions on, I:295–296
C-terminal activation domain effects of, I:287–289
(C-TAD), I:185–186 human exposure and, I:290–292
Cu. See Copper introduction to, I:281–283
Cu2(OH)2CO3. See Malachite Zn, I:9, II:1379, II:1382
Cu2S. See Chalcocite Demethylation
CuFeS2. See Chalcopyrite net, I:449
Cumulative incidence rate, I:266 occurrence of, I:56, I:56f, I:60,
Cuprimine. See Penicillamine I:222–223
CV. See Coefficient of variation Dental amalgams, I:6, I:47, I:391,
CV-AAS. See Cold vapor atomic II:1020
absorption spectrometry DeNOx’ catalysator, II:858
Cyanide, II:833 Deoxyribonucleic acid. See DNA
Cysteine, I:60–61 Depleted uranium (DU), II:1312
Cytochromes, I:431 Deposition, I:49
CZE, Capillary zone electrophoresis of particles, I:51–52
Dermal effects
As and, II:599, II:599t
D U of, II:1329
Daily intake, II:789, II:803–804 Dermal exposure, II:1320
of Ag, II:1210 Desferrioxamine (DFOA), I:501–502
of As, II:584–585 Deterministic effects, I:472
of Be, II:638 Developing countries, metal
of Cd, I:25–26, II:670–672, II:671t toxicology in, I:529–530
of Co, II:745 agricultural fertilizers, I:541–542
of Cr, II:719–720 artisanal gold mining, I:538–540
of Cu, II:766–767 developing countries as global
of food, II:567–568 sources of metals
of Ge, II:803–804 E-waste, I:537–538
of Hg, II:1019–1020 global production of select
of In, II:847 metals, I:531t
lanthanum environmental levels, metal mining deposits, I:531–535
II:905 primary and secondary smelting
of Mo, II:1078–1079 operations, I:535–536
of Pd, II:1116 production of selected mineral
of Sb, II:567–568 commodities, I:532t–534t
of Se, II:1179–1180 recycling of metal-containing
of Sn, II:1250–1253 products, I:536–537
preventive action and research,
I:543
public health problem areas,
I:530–531
toxic metal removal methods,
I:542–543
uranium mining, I:540–541
DFMO. See Difluoromethylornithine
DFOA. See Desferrioxamine
DI. See Depleted uranium
Diagnosis
for Cd, II:707–708
inorganic Pb, II:952–953
of organic Pb, II:956
for Se, II:1202–1203
for Te, II:1226
for Tl, II:1237–1238
Diagnosis and treatment of metal
poisoning, I:488
absorbed poison
elimination, I:497
inactivation, I:497
acute clinical effects of metals,
I:489–490
chelation therapy, I:498–503
chronic clinical effects of metal
toxicity, I:490–493
clinical effects, I:488–493
exposure pattern and, I:488–489
diagnosis, I:493
biochemical investigation, I:495
clinical features, I:494
history of exposure, I:493–494
physiological investigation, I:495
toxicological analysis, I:494–495
general supportive therapy, I:496
control of nervous system effects,
I:496–497
respiration and circulation
maintenance, I:496
water and electrolyte balance
maintenance, I:496
modification of response, I:503
prevention of further absorption
minimizing absorption from GI
tract, I:496
removal from exposure, I:495
treatment, I:495
Dialysis, I:497
Dialysis encephalopathy, II:557
Dietary exposures, II:551, II:552f
Dietary intake
of Ba, II:627
of Be, II:638
of Zn, II:1379
Dietary reference intakes (DRI),
I:286
Diethylenetriaminepentaacetic acid
(DTPA), I:501
 Index i9

Diethylmagnesium (Et2Mg), I:19 absorbed, I:463–464 modeling of, I:199f–201f,

Diffusable Diffusible fraction, I:58 applied, I:463 I:200–204
Difluoromethylornithine (DFMO), assessment, I:462–464 sigmoid curve in, I:202–203,
I:228 concentrations of critical organs/ I:202f–203f
Digestion, of Co targets, I:464 species-to-species extrapolations
by animals, II:747–748 exposure biomarkers of internal, and, I:208–209
by humans, II:748 I:156 epidemiology of, I:266–267
2,3-dimercaptopropanol. See BAL inhaled, I:463 data analysis in, I:274–277
Dimercaprol, I:498–500 internal, I:463–464 data collection in, I:275
Dimethylarsinic acid (DMA), target, I:158 inferences on, I:277–278
I:26–27, I:33, I:243, II:583 threshold, I:199 modeling/observational studies
Dimethylmercury (Me2Hg), I:17–18, in vitro/in vivo, I:199 on, I:267–268, I:269f–270f
I:30, II:1061 Dose reconstruction. See Reverse occurrence of health effects and,
Dimethylselenium (Me2Se), I:30 dosimetry I:266–267
Directed acyclic graphs, I:270 Dose-effect, I:197–200 study designs associated with,
Distribution, II:805, II:1024–1025, dose-response relationships, of As, I:267–268, I:267t
II:1035 II:610–613 risk assessments of, I:471–480,
of Ag, II:1211 epidemiology of, I:266–267 I:472f, I:476t
of Be, II:640–641 data analysis in, I:274–277 considerations for, I:209–212,
of Bi, II:658 data collection in, I:275 I:210f
of Cd, II:677–679 inferences on, I:277–278 of TK, I:63–69, I:64f–66f
of Co, by humans, II:748–749 modeling/observational Dose-response relationships/effects,
of Cu, II:769–771 studies on, I:267–268, I:269f– I:65–66
of Ga, II:790 270f As, II:610–613
of Ge, II:805 occurrence of health effects and, of Ag, II:1212–1214
of In, II:847–848, II:848f I:266–267 of animals, II:1212–1213
of inorganic Sn, II:1256–1257 study designs associated with, of Ba, II:629–632
metabolism of Al, II:553 I:267–268, I:267t of Be, II:641
metabolism of Sb, II:570–571 general considerations for biomarkers of effect and,
metabolism/transport of As, data modeling and, I:204–208, II:649–650
II:588–589 I:206f, I:208t biomarkers of susceptibility and,
of Mn, II:984–986 definitions of, I:199–200 II:650
of Mo, II:1080 general aspects of, I:197–200 genotoxic, II:648
of Pb, II:921–924 interrelationships among, dermal, II:641–642
of Pd, II:1117–1118 I:198–199, I:198f–199f systemic, II:645–646
of Se, II:1185–1186 modeling of, I:199f–201f, toxic action mechanisms and,
of Te, II:1220 I:200–204 II:648–649
of Ti, II:1290 species-to-species extrapolations of Bi
of Tl, II:1232 and, I:208–209 animals, II:659–662
transport of Ba, II:628 risk assessments of, I:471–480, humans, II:659–660, II:662–663
of U, II:1320–1322 I:472f, I:476t of Cd, II:701–704, II:702f
of V, II:1352–1353 of TK, I:63–69, I:64f–66f acute poisoning and, II:686
of W, II:1300 Dose-response, I:197–200 chronic poisoning and, II:686–693,
of Zn, II:1371 considerations II:689t, II:691f, II:706t
Dithiol, I:498 for curves, hormesis/J-shaped/, of Co
Diuresis, I:497 I:203 carcinogenic, II:758–759
DMA. See Dimethylarsinic acid inverted U-shaped in, I:203–204, local, II:750–751
DMPS. See Sodium 2, I:204f mutagenic, II:756–758
3-dimercaptopropane sulfonate curves, hormesis/S/U-shaped in, reprotoxicity and, II:759
DMSA. See Sodium 2, I:200f, I:202–204, I:203f respiratory, II:751–753
3-dimercaptopropane sulfonate data modeling and, I:204–208, systemic, II:754–756
DNA (deoxyribonucleic acid), II:1106 I:206f, I:208t of Cu, II:776–781
Cr, I:46 definitions of, I:199–200 of Ga, II:790–795
proteins, I:240 in era of-omics, I:212 of Ge, II:806–812
synthesis, II:893 general aspects of, I:197–200 of In, II:849–851
Dog whelks, I:453 for immunotoxicology of metals, of inorganic Sn, I:452, II:1265–1276
Dose. See also Benchmark dose; I:380–381 of Mo, II:1083–1086
Benchmark dose level; interrelationships among, of Pd, II:1118–1121
Reference dose I:198–199, I:198f–199f of Pt, II:1265–1276
i10
Dose-response relationships/effects
(Continued )
probabilistic estimation, I:478
threshold-type effects, I:479
toxicodynamics, I:478
toxicokinetics, I:478
stochastic or nonthreshold
effects, I:479
of Sb
animals and, II:573–574
humans and, II:574–576
of Se
carcinogenicity and, II:1197–1198
interactions with other metals,
II:1199–1202
mutagenicity and, II:1197
toxicity, acute/chronic and,
II:1187f, II:1190–1197
of semiconductor compounds,
II:790–795
of Te
animals and, II:1221
humans and, II:1221
systemic, II:1221–1225
of Ti
animals, II:1291–1293
humans, II:1292–1294
of Tl
of animals, II:1234
of humans, II:1234–1236
of U, II:1327–1335
of V, II:1355–1363, II:1357t
of W
animals and, II:1301–1304
humans and, II:1302–1304
Dosimetry, I:142–143
DRI. See Dietary reference intakes
Drosophila melanogaster, I:432
Drugs, I:215. See also specific types of
drugs
DTPA. See Diethylenetriamine
pentaacetic acid
D2EHPA (di[2- ethylbexyl]
phosphoric acid), II:1318
Dust, I:54, II:916
E modeling of, I:198, I:200f–202f
ECC. See Environmental exposure
criteria
Ecological environments, I:10
ECOSAR software, I:437
Ecosystems
metals in, I:433–436
OTCs and, I:27
Ecotoxicology
of Cd
background levels/emissions
and, I:442–443
Index
contamination and, I:443
organism uptakes and, I:443
of Hg
concentrations/emissions/uses
of, I:448
oxidation in, I:449
reduction in, I:449
transformation of, I:448–449
of metals
accumulation/bioavailability/
elimination/uptakes and,
I:430–431
aquatic food chains and, I:431
biological monitoring and,
I:439–440
biomarkers as HI in, I:438–439
defense against/storage of
metals and, I:432–433
individual, I:440–455, I:441f
methods, I:436–437
plant defense systems and,
I:432–433
sources of, I:425–426
of Mo, I:451
of Ni, I:451
of Se, I:451
EDs. See Endocrine disruptors
EDTA (ethylenediaminetetraacetic
acid), I:18–19, I:516
Education, I:516
Effect(s)
attributable risk and
among exposed, I:267
in population, I:267
biomarkers
of critical, I:287, I:290
of critical early, I:156–157
classifying, I:287–289, I:288f
dose-, I:197–200
data modeling and, I:204–208,
I:206f, I:208t
definitions of, I:199–200
general aspects of, I:197–200
interrelationships among,
I:198–199, I:198f
logarithmic model in, I:200–201,
I:200f–201f
power-function model in, I:201,
I:202f–203f
species-to-species extrapolations
and, I:208–209
of TK, I:63–69, I:64f–66f
healthy worker, I:269
lethal toxic, I:290
measurement of, I:271–272
of MeHg, I:274–277
modification of ALAD, I:250
toxic, I:289
Eichhornia crassipes, I:443
Electrolyte balance, I:496
Electron probe microanalysis
(EPMA), I:36–37
Electrophoresis, I:30
Electrospray ionization mass
spectrometry (ESI-MS),
I:27–28
Electrospray mass spectrometry
(ESMS), I:27–28, I:30, I:35–36
Electrothermal atomic absorption
spectrometry (ETAAS), II:1092
Electrothermal vaporization (ETV),
I:32
Element(s)
analysis, I:22–23, I:31–32
identified, I:15
speciation, I:22–23, I:31–32, I:465
”Elemental Speciation in Human
Health Risk Assessment,” I:465
Elimination, I:430–431
of V, II:1353–1354
of U, II:1322–1323
Emissions
control, I:481–482
of metal
into nature, I:425–426
to soil, I:426, I:432
into water, I:426
Emotions, II:988–989
EMs. See Essential metals
Endocrine
effects
of Be, II:646
of Mn, II:998
Mn on, II:998
system
Pb and, II:944
Sb/animal, II:574
Endocrine disruptors (EDs), I:408
Endocytosis, I:430–431
England, II:554–555
Enterohepatic circulation, I:61
Environmental contamination,
I:519–520
Environmental exposure criteria
(EEC), I:438
Environmental exposure/levels,
II:951–952
As and
air and, II:586–587
daily intake/food and, II:584–585
soil and, II:586
tobacco and, II:587
water and, II:585–586
of Ag
air/soil/water and, II:1210
daily intake/food and, II:1210
Al and, II:551, II:552f

to Ba
air/soil/water and, II:626–627
animals/plants and, II:627
of Be
air/soil/water and, II:637–638
animals/dietary intake/plants
and, II:638
daily, II:638
working, II:638–639
of Bi
ambient air/rocks/soil/water
and, II:657
cosmetics/pharmaceuticals and,
II:657
food and, II:657
of Cd
ambient air and, II:673
daily intake/food and, I:25–26,
II:670–672, II:671t
soil/water and, II:672–673
tobacco and, II:673
working, II:673–674, II:674t
of Co
ambient air/soil/water and,
II:745–746
daily intake/food and, II:745
occupational, II:746
of Cu
ambient air/soil/water and,
II:767
daily intake/food and,
II:766–767
working, II:767–768
of Fe, II:880–881
of Ge, II:803–804
of Hg
ambient air/sediments/soil/
water and, II:1020–1022
daily intake/food and,
II:1019–1020
working, II:1022
of In
ambient air/soil/water and,
II:847
daily intake/food and, II:847
of Mn
ambient air/soil/water and,
II:979–981
food and, II:981
working, II:981–982
of Mo
air/soil/water and, II:1079
daily intake/food and,
II:1078–1079
of Ni
air/soil/water and,
II:1093–1094
food and, II:1094
working, II:1095–1096
Index
of Pd
ambient air/soil/water and,
II:1115–1116
daily intake/food and, II:1116
working, II:1116–1117
of Pt
food and, II:1129, II:1130t–1131t
general, II:1127–1129,
II:1130t–1131t
working, II:1129, II:1130t–1131t
Sb and
in air/soil/water, II:568–569
in daily intake/food, II:567–568
in cigarettes, II:569
in working environment, II:569
of Se
ambient air/rocks/soil/water
and, II:1178
daily intake/food and,
II:1179–1180
plants/tobacco and, II:1180
working, II:1180
of Sn
air/soil/water and, II:1253–1255
daily intake/food and,
II:1250–1253
working, II:1255
of Te
air/plants/soil/water and,
II:1219
daily intake/food and, II:1219
of Ti
in air/soil/water, II:1289
in daily intake/food, II:1289
of U
air/rocks/soil/water and,
II:1316–1317
daily intake/food and, II:1315
of V
air/soil/water and, II:1349–1350
daily intake/food and,
II:1350–1351
of W, II:1299
Environmental monitoring, I:520
Enzyme poisoning, I:431
Epidemiology in metal toxicology,
I:265
assessment of effects, I:272–274
BMD, I:274–277
classification of, I:267t
control population, I:266
cumulative incidence rate, I:266
exposure assessment, I:270–272
incidence, I:266
inference, I:277–278
life-table method, I:266–267
observational, I:266
prenatal and postnatal exposures,
I:270f
i11
study design, I:267–268
study population, I:266, I:268–270
Epigeneticity of metals, II:1106–1107
Cd and, I:183
in development of cancer,
I:181–182
introduction to, I:173
metal compounds and, I:180–184
Ni and, I:183–184
EPMA. See Electron probe
microanalysis
ERK. See Extracellular signal
regulated kinase
ERK5. See Extracellular signal
regulated kinase-5
Erythrocyte superoxide dismutase
(ESOD), I:295
Erythrocytes, II:927–928
Escherichia coli, II:610
ESI-MS. See Electrospray ionization
mass spectrometry
ES-MS. See Electrospray mass
spectrometry
ESOD. See Erythrocyte superoxide
dismutase
Essential metals (EMs), I:11
calcium and, I:175–176
Cu and, I:177
deficiency risks associated with
basic concepts in, I:283–284,
I:284f
conclusions on, I:295–296
effects of, I:286–290
human exposure and, I:290–292
introduction to, I:281–283
Fe and, I:176–177, I:293
immune system and, I:382–383
Mg and, I:176
toxic metals and, I:177–179
toxicity risks associated with,
I:281–283, I:284f, I:288f, I:291f
Zn and, I:176, I:295
Estrogen, I:225
Estuaries, biogeochemical transport
of metals into, I:428–429
Et2Mg. See Diethylmagnesium
ETAAS. See Electrothermal atomic
absorption spectrometry
Ethylenediaminetetraacetic acid. See
EDTA
Ethylmercury, II:1019
ETV. See Electrothermal vaporization
European Union, I:12–13, I:444, I:470,
I:483
European Union Scientific
Committee on Food, I:291
European Virtual Institute for
Speciation Analysis (EVISA),
I:38
i12 Index

EVISA. See European Virtual general aspects of, I:46–47 As and, II:584–585
Institute for Speciation by inhalation, I:47–48 In and, II:847
Analysis toxicology of, I:10–11 V in, II:1350–1351
E-wastes, I:9 uses of critical organ Ag and, II:1210
EXAFS. See Extended X-ray concentration in, I:69–70, I:70f Bi and, II:657
absorption fine structure uses of indicator media for Cd and, I:25–26, II:670–672, II:670t
spectroscopy estimation of, I:69–70, I:70f chains, I:10
Excretion, II:802, II:1025, II:1035–1036 indicator media use, I:69 aquatic, I:431
of Ag, II:1211 biological monitoring programs, Co and, II:745
of Ba, II:628–629 I:69–70 contaminated, I:11
of Be, II:640–641 hair samples, I:69 Cr and, II:719
of Bi, II:658 head hair, I:69, I:70f Cu and, II:766–767
of Cd, II:679–680 by inhalation, I:47 daily intake of, II:567–568
of Co, by humans, II:749 cogeneration plants, I:47 exposure to metals through, I:47–48
of Cr, II:722 condensation aerosols, I:48 Hg and, II:1019–1020
of Cu, II:773–774 metal aerosols, I:48 Mn on, II:981
of Ga, II:790 release of mercury vapor, I:47 Mo and, II:1078–1079
gastrointestinal, I:60–61 tetraethyllead, I:47–48 Ni and, II:1094
of Ge, II:805–806 toxic and irritant gases, I:48 Pd and, II:1116
of Hg, II:1025 Exposure assessment, I:270–272. See Pt and, II:1129, II:1130t–1131t
of In, II:848, II:848f also Human PBPK tool kit sampling/sample preparation of,
of inorganic Sn, II:1257 development I:23–27, I:515
metabolism general background, I:141–142 Se and, II:1179–1180
of As, II:590–591 PBPK modeling, I:142–143 Sn and, II:1250–1253
of Al, II:553 general principles, I:142 Te and, II:1219
of Sb, II:571 biomonitoring and interpretation, of Ti, II:1289
of metals I:143–144 U and, II:1315
gastrointestinal, I:60–61 Extended X-ray absorption fine webs, I:450
mechanisms/pathways in, structure spectroscopy Food and Agricultural Organization
I:60–63, I:62f (EXAFS), I:36–37 (FAO), I:482–483
rate/biological half-time, I:62–63 Extracellular signal regulated kinase Fractionation, I:23
renal, I:61–62, I:62f (ERK), I:185 France, I:352, II:758–759
of Mn, II:987 Extracellular signal regulated Free ion activity model (FIAM),
of Mo, II:1080 kinase-5 (ERK5), I:185 I:434
of Ni, II:1097 Friberg, Lars, I:4
pathways and mechanisms of, I:60 Friedreich ataxia, II:892
of Pd, II:1118 F Fucus species, I:440
of Pt, II:701–702 FAO. See Food and Agricultural Fuels, automobile, I:24–25
rate-biological half-time, I:62–63 Organization
renal, I:61–62 Forward dosimetry, I:142–143
of Se, II:1188 Fatigue, II:557–558 G
of Te, II:1220 FDA Advisory Committee on Ga. See Gallium
of Ti, II:1291 Protocols for Safety Gallium (Ga)
of Tl, II:1232–1233 Evaluation, I:208, I:208t analytical methods/problems,
of U, II:1322–1323 Fe. See Iron II:787–788
of W, II:1300–1301 Fenton reaction, I:20 associated with, II:794–795
of Zn, II:1377 Ferric dextran, II:851 biological fluid levels of, II:790
Expected number of cases, I:266–267 Ferroportin, II:885 chemical/physical properties of,
Exposome, I:151–152 FIAM. See Free ion activity model II:787
Exposure Filters, I:24–25 dose-response relationships/effects
aspects, I:46–47 Findeisen’s model, I:52 of, II:790–795
dermal, II:639 Fingernails, I:495 environmental exposure/levels of,
environmental exposure levels, Fish, I:450, II:804 II:789
I:164, II:789 consumption of, I:12–13, I:27 metabolism of
experimental, II:1361–1362 contamination of, I:5, I:48 biological half-time, II:790
food and drinking water, I:48–49 freshwater, II:567 distribution/excretion, II:790
to metals, I:45 mercury in, I:5, I:450 ingestion/inhalation, II:789
through drinking water/food, Fly ash, I:47 production/uses of, II:788–789,
I:48–49 Food, I:46–47, I:520, II:789, II:916 II:788f

Gallium semiconductor compounds,
II:788
exposures of workers, II:792
in groundwater, II:789
hazard, II:792–793
immunological effects in workers,
II:793
levels in biological fluids, II:790
pulmonary effects in workers, II:793
reproductive effects in workers,
II:793
uses, II:788–789
Gamma-glutamyltransferase (GGT),
I:61
Gas chromatography (GC), I:27, I:30
Gases
absorption of, I:48
inhaled, I:48
Gasoline, I:6, I:47–48
Gastrointestinal effects
of As, II:599
of Al, II:554–555
Gastrointestinal excretion, of metals,
I:60–61
Gastrointestinal scarring, II:897
Gastrointestinal toxicity, II:897
Gastrointestinal tract, I:56, I:221,
I:489–490, I:496
Pb and, II:920–921, II:924, II:930
Sb/human, II:574
Gavia immer, I:450–451
GC. See Gas chromatography
GCS. See Glucocortisteroids
GE. See Gel electrophoresis
Ge. See Germanium
Gel electrophoresis (GE), I:27, I:30–31
Gelatin, II:851
Gender, I:134
Gene-environment interaction, I:239
analysis and interpretation,
I:241–242
arsenic, I:242–247
beryllium, I:247–248
cadmium, I:248–249
choice of polymorphisms, I:241
cobalt, I:249–250
epigenetics of metals, I:240–241
genes of concern, I:240
lead, I:250–254
manganese, I:254–255
mercury, I:255–258
method of detection, I:241
nickel, I:258
platinum, I:258–259
Gene(s)
environment interactions,
II:926–927
metal toxicology and, I:239–242
expression, II:1105–1106
Index
methyltransferase, I:240
susceptibility, I:240
General Air Pollution and Human
Health with Special Reference
to Long-Term Effects, I:207
Generalized Toxicokinetic Modeling
System for Mixtures (GTMM),
I:68
Genotoxicity, II:648, II:1102–1105
of As, II:609–610
biomarkers of effects in, I:166
Genotyping, I:250, I:252
German Commission for the Inves-
tigation of Health Hazards of
Chemical Compounds in the
Work Area, II:560
Germanium (Ge), I:58–59, I:58f
analytical methods/problems
associated with, II:800–801
biological monitoring of, II:806
chemical/physical properties of,
II:800
dose-response relationships/effects
of, II:806–812
environmental exposure/levels of,
II:803–804
production/uses of, II:801–803
teratogenicity, II:812
toxicokinetics of, II:804–806
treatment trials for, II:812–813
Germany, I:352
GGT. See Gamma-glutamyltrans-
ferase (GGT)
GFAAS. See Graphite furnace atomic
absorption spectrometry
Glucocortisteroids (GCS), II:651
Glutathione (GSH), I:222, II:593–594
intracellular, I:190
reductase, I:188
secretion, I:60–61
as toxic metal, I:178
toxic metal-binding molecules,
I:178–179
Glutathione peroxidase (GSHPx),
I:289
Gold (Au), I:385–386, II:818
biological monitoring, II:830–831
dose-response relationships,
II:825–830
environmental levels and exposures
dental treatment, II:821–822
food and daily intake, II:821
general environment, II:821
therapeutic, II:822
working environment, II:821
kinetics and metabolism, II:822
absorption, II:822
biological half-times, II:824
distribution, II:822–823
i13
excretion, II:824
gold nanoparticles, II:825
human tissues and biological
fluids levels, II:824–825
metabolism, II:823–824
methods and problems of analysis,
II:819–820
physical and chemical properties,
II:818
production, II:820
in treatment of rheumatoid
arthritis, II:819f
uses
gold, II:820
gold compounds, II:821
gold nanoparticles, II:821
Gold lung, II:829–830
Gold kushta, II:828
Gold mining, II:831
arsenic, II:832
cyanide, II:833
hair mercury concentrations,
II:837t
lead, II:839
mercury, II:833–838
silica, II:832
urinary mercury concentrations,
II:835t–836t
Graphite furnace atomic absorption
spectrometry (GFAAS),
II:819–820
Greenland, I:443
GSH. See Glutathione
GSHPx. See Glutathione peroxidase
GTMM. See Generalized Toxicoki-
netic Modeling System for
Mixtures (GTMM)
H
H2O2. See Hydrogen pyroxide
Haber-Weiss reactions, I:189–190
Hair, I:431, I:495, II:597–598
head, I:69
samples, I:69
Zn, II:1375
Hall-Héroult process, II:550
Halogen ligands, I:388
Hamster ovary cells, I:224–225
Hazard identification, I:464–465. See
also Risk assessment
chronology of observations of carci-
nogenicity, I:468, I:469f
classification
according to ACGIH, I:471
according to USEPA, I:470–471
in European Union, I:470
epidemiological studies, I:479–480
human data, I:466
i14
Hazard identification (Continued )
analytical epidemiological
studies, I:466–467
causality for cancer, I:467
Hill’s criteria of causality, I:467
IARC Group 2, I:468–470
IARC Group 2A, I:469
IARC Group 2B, I:469–470
in vitro and in silico data, I:471
in vivo and in vitro data, I:467–468
mechanism of action, I:465–466
mode of action, I:466
probabilistic estimation of dose-
response relationships,
I:478–479
quantitative toxicological analysis,
I:471–475
short-term and long-term studies in
animals, I:475
speciation, I:465
Hazard index (HI), I:231, I:234,
I:438–439
As and, I:509–510
MeHg as, I:510
Pb as, I:509–510
reduction of exposure associated
with, I:510
Hazard quotient (HQ), I:231, I:234
Head hair, I:69
Health
effects of Mn, II:987–988
examinations, I:515–516
human, I:444–445, I:451
metals and, I:4–7
Healthy worker effect, I:269
Heart, II:811
disease, II:928
strokes and, II:603, II:943
Hematological effects, II:808,
II:997–998, II:1359
of As, II:600
of Be, II:646
Hematopoietic tissues, II:607
Heme oxygenase1 (HO-1), II:881
Hemocyanin, I:431
Hemoglobin, I:431
Hemoglobulin, II:881–883, II:884f
Hemolysis, II:779
Hemopoietic effects, of metals,
I:490–492
Hepatic effects, II:1330
of As, II:600
of Hg compounds, II:1050
of metals, I:490
Hepatic mechanisms, II:1324
Hepatotoxicity, II:897
Hepcidin, II:885–886
Hereditary hemochromatosis (HH),
II:890
Index
Hexachlorplatinic acid, I:388
HFCs. See High frequency of SCEs
Hg. See Mercury
HG-AAS. See Hydride generation
atomic absorption
spectrometry
HH. See Hereditary hemochroma-
tosis
HI. See Hazard index
HIF-1. See Hypoxia-inducible
factor 1
HIF-prolyl hydroxylases (HPHs),
I:185–186
High frequency of SCEs (HFCs), I:166
High-performance liquid chroma-
tography (HPLC), I:27–28
High-resolution scanning electron
microscopy (HR-SEM), I:36–37
Hill’s criteria, I:467
Histone acetylation, II:1106–1107
HLA. See Human leukocyte antigen
HO-1. See Heme oxygenase1
Homeostasis, II:887–888
Homeostatic model, I:291t
Hockey-stick method, I:275
Hormesis
J-shaped/inverted U-shaped, I:203,
I:204f
S/U-shaped, I:200f, I:202–204,
I:203f–204f
Host-resistance challenge systems,
I:381–382
Housekeeping, I:512
HPHs. See HIF-prolyl hydroxylases
HPLC. See High-performance liquid
chromatography
HQ. See Hazard quotient
HR-SEM. See High-resolution
scanning electron microscopy
Human(s), II:641–642, II:646–647,
II:807, II:1103–1105, II:1265,
II:1268, II:1352
biological half-time of Sb and,
II:572
carcinogenic to, I:467–470
cell culture, II:1304
Co and
absorption/digestion/inhalation
of, II:748
distribution/excretion of,
II:748–749
data, I:466–467
dose-response relationships/effects
of, II:1213–1214
of Te, II:1221
excretion, II:571
exposures, I:481–482
risks associated with EMs and,
I:290–292
health, I:444–445, I:451
risks to, II:1382
Sb and
dose-response relationships/,
II:574–575
on gastrointestinal tract, II:574
immunology/, II:575
on respiratory system, II:574–575,
II:575f
on skin, II:575
Tl and, II:1234–1236
W and, dose-response
relationships/ effects of,
II:1302–1304
Human leukocyte antigen (HLA),
I:364
Human PBPK tool kit development,
I:144. See also Exposure
assessment
arsenic, I:144–145
cadmium, I:145
biomonitoring data, I:145–148
intake rates, I:148, I:148t
sensitive subpopulations, I:148
and exposome, I:151–152
lead, I:149–151
mercury, I:149
Human umbilical vein endothelial
cells (HUVEC), I:187
HUVEC. See Human umbilical vein
endothelial cells
Hydride generation atomic
absorption spectrometry
(HGAAS), I:32–33
Hydrogen pyroxide (H2O2),
I:184–185
Hydrolysis, I:20–21
Hydroxides, I:19, II:551
Hydroxyl radical (OH), I:184–185
Hypercalcemia, II:794
Hyperphosphatemia, II:908
Hypersensitivity
Au and, I:385–386
Be and, I:384
Co and, I:385
Cr and, I:385
Hg and, I:386–387
induced by immunotoxicology of
metals, I:383–384
Type I (anaphylactic/immediate),
I:383
Type II (antibody-mediated
reactions), I:383
Type III (immune-complex
mediated reactions), I:383
Type IV (cell-mediated reactions),
I:383–384
reactions caused by metals,
I:384–388

Hypertension, II:604
Hypothalamus, I:299–300
Hypoxia-inducible factor 1 (HIF-1),
I:185–186
I introduction to, I:379–381
IAEA. See International Atomic
Energy Agency
IARC. See International Agency for
Research on Cancer
ICOH. See International Commission
on Occupational Health
ICP-AES. See Inductively coupled
plasma-atomic emission
spectrometry
ICP-MS. See Inductively coupled
plasma-mass spectrometry
ICP-OES. See Inductively coupled
plasma optical emission
spectroscopy
ICRP. See International Commission
on Radiological Protection
IEC. See Ion-exchange chromatog-
raphy
IEUBK Model. See Integrated
Exposure Uptake BioKinetic
Model
Immune
complex mediated reactions (Type
III hypersensitivity), I:383
system, II:1041–1042
EMs and, I:382–383
Immunity, II:1376
Immunological mechanisms,
II:1324–1325
Immunology, II:998
As and, II:601
Sb/human, II:574–576
Immunostimulation, nonspecific,
I:390–391
Immunosuppression, induced by
immunotoxicology of metals,
I:381–382
clinical immunosuppressive effects
of, I:382
experimental host-resistance
systems and, I:381–382
general considerations for, I:381
in vitro studies and, I:381
in vivo studies and, I:381
Immunotoxicology, II:945
of metals, II:945
autoimmunity and, I:391–392
dose-response considerations in,
I:380–381
Hg and, I:390–391
host-resistance challenge systems
and, I:381–382
Index
hypersensitivity induced by,
I:383–384
hypersensitivity reactions caused
by, I:384–388
immunosuppression induced by,
I:381–382
mechanisms in, I:380
nonspecific immunostimulation
induced by, I:390–391
other protein interactions and,
I:389–390
Pb and, I:390–391
protein interactions and,
I:388–389
xenobiotics and, I:392–393
In vitro fertilization (IVF), I:406
Incidence, I:266
India, II:585–586
Indium (In), I:9
analytical methods/problems
associated with, II:845–846
biological fluids and, II:849
chemical/physical properties of,
II:845
dose-response relationships/effects
of, II:849–851
environmental exposure/levels of
ambient air/soil/water and,
II:847
daily intake/food and, II:847
interactions of, II:851
metabolism of
biological half-time, II:848
distribution/excretion,
II:847–848, II:848f
ingestion/inhalation, II:847
production/uses of, II:846, II:846f,
II:846t
Inductively coupled plasma optical
emission spectroscopy
(ICP-OES), II:582
Inductively coupled plasma-atomic
emission spectrometry
(ICPAES), I:30, I:33–34, II:550
Inductively coupled plasma-mass
spectrometry (ICP-MS), I:30,
I:32, I:34–35
Infant neurodevelopment, I:305
Infants, I:517–518
Inference, I:277–278
Ingestion, II:804, II:916–917,
II:1023–1024, II:1034–1035
absorption after, I:56
foodstuffs, I:56
gastrointestinal absorption, I:57
gastrointestinal route, I:56
inorganic salts of metals, I:57
methyl mercury, I:56
i15
oral dose of metal salt, I:57
paracellular migration, I:57
respiratory tract clearance,
I:57–58
absorption/deposition of metals
after, I:56–58, I:56f, I:58f
of Ag, II:1211
of Ba, II:628
of Be, II:639–640
of Cu, II:768–769
of Ga, II:790
of In, II:847
of inorganic Sn, II:1256
metabolism of As, II:587–595
metabolism of Sb, II:569–572
of metals, I:56–58, I:56f, I:58f
of Mn, II:983–984
of Mo, II:1079–1080
of Pb, II:916–917
of Pt, II:1129–1133
of Te, II:1220
of U, II:1319–1320
of V, II:1352
Inhalation, II:801, II:915–916,
II:923–924
absorption after, I:49
clearance of particles, I:52–56
deposition of particles, I:51–52
gases and vapors, I:51
MMAD, I:50
volume or mass distribution of
particles, I:50f
of Ag, II:1211
of Ba, II:627–628
of Be, II:639, II:642–646
of Co
by animals, II:747–748
exposure by, I:47
cogeneration plants, I:47
condensation aerosols, I:48
metal aerosols, I:48
release of mercury vapor, I:47
tetraethyllead, I:47–48
toxic and irritant gases, I:48
by humans, II:748
of Ga, II:789
of In, II:847
of inorganic Sn, II:1255–1256
metabolism of Sb, II:569–572
of Mn, II:982–983
of Mo, II:1079
of Pt, II:1129–1133
of Te, II:1219
of U, II:1318
of V, II:1351–1352
Inorganic Chemistry (Bjerrum), I:15–16
Inorganic compounds, I:17
As and, I:5
metal, I:18
i16
Institute for Reference Materials and
Measurements, I:38
Institute of Medicine (IOM),
I:285–286
Integrated Exposure Uptake
BioKinetic Model (IEUBK
Model), I:149
International Agency for Research on
Cancer (IARC), I:8–9, I:208–209,
I:467, II:560, II:576, II:792
International Atomic Energy Agency
(IAEA), I:37
International Commission on
Occupational Health (ICOH),
I:4, I:15, I:155–156, I:483
International Commission on
Radiological Protection
(ICRP), I:52
International Labour Organization
(ILO), I:4
International Nickel company, I:352
International Programme on
Chemical Safety (IPCS), I:462
Environmental Health Criteria,
I:285
Health Criteria Documents of, I:5–7
main objective of, I:4
Scientific Committee of, I:5–7
International Standardization
Organization (ISO), I:38
International Symposium on the
Immunotoxicity of Metals and
Immunotoxicology, I:379–380
International Union of Pure and
Applied Chemistry (IUPAC)
definitions/glossary of, I:23
guidelines for external quality, I:158
assessment, I:158, I:161–162
recommendations, I:285
Intestines, II:1049
Intracellular sequestration, I:307
Iodides, I:19
Iodo(methyl)magnesium. See
MeMgI
IOM. See Institute of Medicine
Ion-exchange chromatography (IEC),
I:29
Ionic mimicry, I:46
Ions, I:16
biosensors for monitoring metal,
I:36
properties of metal
formation of, I:19–20
hydrolysis and, I:20–21
as Lewis acids, I:20
redox potential of, I:20, I:20t
IPCS. See International Programme
on Chemical Safety
Iraq, I:5
Index
IREs. See Iron-responsive elements
Iridium (Ir), II:855
dose-response relationships,
II:872–875
environmental levels and exposure,
II:858–868
human tissues and biological
fluids, II:870–872
kinetics and metabolism, II:869–870
methods and problems, II:856–857
physical and chemical properties,
II:855–856
production, II:857–858
uses, II:858
Iron (Fe), I:10, I:190, I:446
absorption, II:886–887, II:886f
analytical methods/problems
associated with, II:880
biological function of, II:881–888,
II:882t–883t, II:884f, II:
886f–887f
carcinogenicity of, I:368–369,
II:893–894
chemical/physical properties of,
II:880
conclusions on, II:896
deficiency, diseases of, II:888–889
dextran, I:368
environmental exposure/levels of,
II:880–881
essential metals and, I:176–177, I:293
hemoglobulin, II:881, II:884f
homeostasis, II:887–888
intakes of, I:11–12
metabolism of, II:881–888, II:
882t–883t, II:884f, II:886f–887f
pathophysiology, II:888–894
in metal-metal carcinogenic
interactions, I:225–226
overdose, II:896
overload
diseases of, II:888–889, II:891t
tissue damage mechanisms in,
II:891–894
oxide, I:368
poisoning, II:896–898
preparations, II:896
production/uses of, II:880
proteins, II:882t–883t
non-heme, I:22
as toxic metal, I:174
Iron regulatory proteins (IRPs), I:22,
I:176, II:888
Iron-responsive elements (IREs),
I:176, II:887
IRPs. See Iron regulatory proteins
Ischemic heart diseases, II:560, II:603
ISO. See International Standardi-
zation Organization
Itai-Itai disease, I:6–7
Italy, I:528
IVF. See In vitro fertilization
J
Japan, I:5, I:48–49, I:220, II:595,
II:595t, II:599, II:610–611
JNK. See C-jun N terminal kinase
Joint FAO/ WHO Expert Committee
on Food Additives (JECFA), I:47
Jurkat cells, I:189
K
Kidney(s), I:12, I:66, II:778, II:805,
II:808, II:1358
Pb and, II:924, II:940–942
Sb/animal, II:573–574
urine and, I:159–160
weight, II:680–681
Kinetics
of Ba
distribution/transport, II:628
excretion, II:628–629
ingestion and, II:628
inhalation and, II:627–628
of Be
absorption/ingestion/inhalation
and, II:639–640, II:642–646
distribution/excretion/transport
and, II:640–641
Pt and, II:1129–1133, II:1130t–1131t
sampling, I:163–164
of Se, II:1184–1189
absorption, II:1184–1185
biological half-time, II:1188–1189
biotransformation, II:1186–1187
distribution, II:1185–1186
excretion, II:1188
Kjellstrom-Nordberg model, I:67–68
Kolaviron, I:225
Korean National Health and
Nutrition Examination Survey
(KNHANES), I:323
L
L1. See Deferiprone
Labeling, I:481–482
LA-DRC-ICP-MS. See Laser ablation
dynamic reaction cell
inductively coupled plasma
mass spectrometry
Lakes, I:10
Lanthanides, II:904
Lanthanum (La), II:903
biological monitoring, II:907
chemical properties, II:903–904

effects and dose-response relation-
ships, II:907
environmental levels and exposure
air, II:905–906
food and daily intake, II:905
soil, II:905–906
water, II:905–906
working environment, II:906
metabolic interactions, II:906–907
metabolism, II:906–907
methods, II:904
physical properties, II:903–904
poisoning and prevention,
II:907–908
problems of analysis, II:904
production, II:904
uses, II:904–905
Laser ablation dynamic reaction cell
inductively coupled plasma
mass spectrometry (LA-DRC-
ICP-MS), I:31
Latin America, I:535
LC. See Liquid chromatography
Lead (Pb), I:62, I:149–151, I:446–447
acetate, I:216
background on, II:911
biomarkers of effects for, I:158
carcinogenicity of, I:8–9, I:173,
I:366–368
animal models in, I:367
epidemiological observations of,
I:366–367
evaluation of, I:367–368
children and, I:221, II:954
paint and, I:10, II:919
compounds, I:30
detoxification, I:18–19
endocrine system and, II:944
flooding and, I:10
gastrointestinal tract and,
II:920–921, II:924, II:944
gold mining, II:839
as HI, I:509–510
immunotoxicology of metals,
I:390–391
inorganic
analytical methods/problems
associated with, II:912–914
biological monitoring of,
II:927–933, II:930f, II:932t, II:934f
chemical/physical properties of,
II:911–912
diagnosis/prognosis/treatments
for, II:952–954
exposure classifications/
standards for, II:951–952
exposure to, II:914–919, II:915f,
II:918f, II:919t
organ effects of, II:933–945
Index
reproduction and, II:946–949
risk assessments for, II:949–951
toxicokinetics of, II:919–927,
II:922f–923f, II:925f
kidneys and, II:924, II:940–942
male reproduction and, II:948–949
metal toxicology and, I:250–254
in metal-metal carcinogenic
interactions, I:226
metal-metal interactions and,
I:221–222
neonatal exposure/developmental
effects from, I:417–418
neurotoxic effects of, I:8
organic
analytical methods/problems
associated with, II:954
biological monitoring of, II:955
chemical/physical properties of,
II:954
diagnosis/prognosis/treatments
for, II:956
organ effects of, II:955–956
production/uses of, II:954
toxicokinetics of, II:954–955
paints, I:10
prenatal exposure/developmental
effects of, I:414–417
production/uses of, I:10, II:626
in tetraethyl gasoline, I:6
xenobiotics/autoimmune diseases
by, I:392–393
Leaded gasoline, I:47–48
Leukopenia, II:1225
Lewis acids, I:20
Li. See Lithium
Life-table method, I:266–267
Lipophilic metal complexes,
I:429–430
Liquid chromatography (LC),
I:27–30, I:28f
Lithium (Li), I:9
acute effects, II:971–972
analytical methods, II:970
biomonitoring, II:973
chronic effects
CNS, II:972–973
kidney, II:972
other effects, II:973
thyroid, II:972
introduction, II:969–970
levels in environment, II:970
lithium intoxication, treatment and
prevention, II:973–974
metabolism, II:971
physical and chemical properties,
II:970
sources of exposure
dietary exposure, II:970–971
i17
drinking water, II:971
medication, II:971
occupation, II:971
Liver, II:804, II:1358
cancer, II:607, II:608t
effects on, II:777–778
role of, II:773
Sb/animal, II:573
LLLT. See Low-level laser therapy
LOAELs (lowest-observed adverse
effect levels), I:210, I:292–293,
II:611, II:950
Low-level laser therapy (LLLT),
II:793–794
Lung(s)
acute/chronic diseases of, I:53
airborne metals and, I:46, I:49
cancer, I:274, II:604t, II:605–606
clearance, peripheral, I:54–55
deposition, II:1290
fibrosis, II:555
Mn on, II:987–988
parenchyma, II:752–753
particle deposition in, I:52
toxicity, biomarkers of effects in,
I:165–166
Lysis, I:32
Lysosomal membranes, II:893
M
MAC (maximum allowable concen-
trations)
developmental problems associated
with, I:4
establishment of international, I:4
Macroalgae, I:440
Magnesium (Mg), I:176
Malachite (Cu2(OH)2CO3), II:766
MALDI-MS. See Matrix-assisted laser
desorption ionization mass
Manganese (Mn), I:447–448
analytical methods/problems
associated with, II:976–977
carcinogenicity of, I:369
chemical/physical properties of,
II:976
concentrations, II:1000–1002
effects on
cardiovascular, II:997
endocrine, II:998
health, II:987–999
lungs, II:994–996
reproductive, II:996–997
environmental exposure/levels of
ambient air/soil/water and,
II:979–981
food and, II:981
working, II:981–982
i18
Manganese (Mn) (Continued )
guidelines/regulations on, II:
999–1000
male reproduction and, II:408–409
metabolism of, II:986–987
excretion/, II:987
neurotoxic effects of, I:8
occurrence/production/uses of,
II:977–979
toxicokinetics of
absorption/ingestion/
inhalation/, II:982–984
distribution/excretion/,
II:984–986
Manipur Ophiolitic Complex,
II:859
MAPK. See Mitogen-activated
protein kinase
MAPK kinase kinases (MAPKKK),
I:185
MAPK kinases (MAPKK), I:185
MAPKK. See MAPK kinases
MAPKKK. See MAPK kinase kinases
Margin of exposure (MoE), I:275
Marine environments, I:452–454
Marine organisms, II:584
Mass median aerodynamic diameter
(MMAD), I:50, II:1211–1212
Mass spectrometry (MS), I:34–36.
See also specific types
Massachusetts, II:643–644
Matrix-assisted laser desorption
ionization mass spectrometry
(MALDI-MS), I:31, II:1092
Maximum allowable concentrations.
See MAC
MCMA. See Mexico City
Metropolitan Area (MCMA)
Me2Hg. See Dimethylmercury
Me2Se. See Dimethylselenium
Me3Bi. See Trimethylbismuth
Me3Sb. See Trimethylantimony
Me4Sn. See Tetramethyltin
Mechanism of action, I:465–466
MECC. See Micellular electrokinetic
capillary chromatography
Medical devices, implanted, I:47
Medical Removal Protection
program, I:513
MeHg. See Methylmercury
MEKK 1. See Mitogen-activated
protein kinase kinase 1 (MEKK
1)
Memory, II:557–558
Menkes disease, I:240, II:768, II:771
Mercury (Hg), I:18–19, I:58–59, I:149.
See also Ethylmercury; Methyl-
mercury
alcohol and, I:215
Index
analytical methods/problems
associated with, II:1016–1017
chemical/physical properties of,
II:1015–1016
in CNS, I:489
compounds, hepatic effects of,
II:1050
compounds, organic, II:1045–1062
in dental amalgams, I:6, I:47, I:391,
II:1020
ecotoxicology of
concentrations/emissions/uses
of, I:447
oxidation in, I:449
reduction in, I:449
transformation of, I:448–449
effects on humans by, I:4
elemental, II:1022–1045,
II:1031f–1032f
in environmental disasters,
I:391–392
environmental exposure/levels of
ambient air/sediments/soil/
water and, II:1020–1022
daily intake/food and,
II:1019–1020
working, II:1022
in fish, I:5, I:450
flux, global, I:449
gold mining, II:833–838
hair mercury concentrations,
II:837t
hypersensitivity and, I:386–387
immunotoxicology of metals and,
I:390–391
inorganic, I:324–325, I:418
inorganic mercuric, II:1063
introduction to, II:1014–1015
mercuric, II:1034–1045, II:1038f
metabolism of, II:1045–1051
metal-metal interactions and,
I:218–223
monitoring of, I:27
neonatal exposure/developmental
effects from, I:418
neurotoxic effects of, I:8
poisoning, II:1025–1029,
II:1040–1043
in fisherman, I:5
in Japan, I:4, I:48–49
in Sweden, I:4–5
prenatal exposure/developmental
effects of, I:414–415
production/uses of, I:10,
II:1017–1019, II:1018f
renal effects of, II:1041,
II:1046–1047
in sludge of lakes, I:10
uptakes of, I:450
urinary mercury concentrations,
II:835t–836t
vapors, I:6, I:47, II:1025–1029,
II:1063
xenobiotics/autoimmune diseases
by, I:392–393
Metabolism, II:1360–1361
of As, I:242–247, II:600–601
absorption/, II:610
biological half-time/, II:591
biotransformation/, II:589–590
distribution/transport/,
II:588–589
excretion/, II:590–591
ingestion/, II:588
toxicity/, II:591–595
of Ag
absorption/ingestion/
inhalation/, II:1211
biological half-time/,
II:1211–1212
distribution/excretion/, II:1211
of Al
absorption and, II:551–553,
II:552t
biological monitoring, II:552t,
II:553–554, II:554f
distribution and, II:553
excretion and, II:553
of Bi
absorption, II:657–658
biological half-time/, II:659
distribution/excretion/, II:658
of Cd, I:11–12, II:680
of Co
animals’ absorption/inhalation
and, II:747–748
animals’ distribution/excretion
and, II:748–749
humans’ absorption/digestion/
inhalation and, II:748
humans’ distribution/excretion
and, II:748–749
of Cu, II:768–774
absorption/ingestion, II:768–769
biological half-time, II:774
distribution, II:769–771
excretion, II:773–774
of Fe, II:881–888, II:882t–883t,
II:884f, II:886f–887f
pathophysiology, II:888–894
of Ga
biological half-time, II:790
distribution/excretion, II:790
ingestion/inhalation, II:789
heme, II:930–931, II:930f, II:932t
of Hg, inorganic, II:1022–1045
of Hg, organic, II:1045–1062
of In

biological half-time, II:848
distribution/excretion,
II:847–848, II:848f
ingestion/inhalation, II:847
of inorganic Sn
absorption/ingestion/
inhalation, II:1255–1256
biological half-time, II:1257
distribution/excretion,
II:1256–1257
of metals, I:46
of Mn, II:986–987
excretion, II:987
of Mo
absorption/ingestion/inhalation,
II:1079–1080
biological half-time, II:1080–1081
distribution/excretion, II:1080
of Ni, II:1096
absorption, II:1096–1097
biological half-time, II:1097–1098
excretion, II:1097
nucleotide, II:931–932
of Pb
toxicokinetics, II:919–927
of Pd
absorption, II:1117
distribution/excretion,
II:1117–1118
of Pt
absorption/ingestion/
inhalation, II:1129–1132
biological fluids, II:1132–1133
biological monitoring, II:1133
kinetics and, II:1129–1132,
II:1134t
of Sb
absorption, II:569
distribution, II:570–571
excretion, II:571
ingestion and, II:570
inhalation and, II:569
of Se, II:1180–1181
of Te
absorption/ingestion/inhalation,
II:1219–1220
biological half-time, II:1220
distribution/excretion, II:1220
of Ti
absorption, II:1290
biological half-time, II:1291
distribution/excretion,
II:1290–1291
of Tl
absorption, II:1231–1232
biological half-time, II:1233
distribution/excretion,
II:1232–1233
toxicology of metals and, I:11–12
Index i19
of U, II:1320–1322 of Cr, I:8–9, I:173, II:738–739
of W animal models in, I:356–357
absorption, II:1300 epidemiological observations of,
biological half-time, II:1301 I:355–356
distribution/excretion, II:1300 evaluation of, I:357–358
of Zn in vitro studies, I:357
absorption/excretion/biological of Cu, II:780
half-life, II:1375–1377 of metals, I:8–9, I:173
Metabolites, I:431 of Mn, I:369
Metal(s). See also Essential metals of Ni, I:8–9, I:94–95
absorption/deposition of, I:49–58 animal models in, I:353–354
after ingestion, I:56–58, I:56f, I:58f epidemiological observations of,
after inhalation, I:49–56, I:50f, I:352–353
I:51t evaluation of, I:354–355
aerosols, I:48 of Pb, I:8–9, I:173, I:366–368
airborne, I:46 animal models in, I:367
analytical methods/general epidemiological observations of,
chemistry/sampling/ I:366–367
speciation of, I:17t, I:21t, I:28f, evaluation of, I:367–368
I:45–74 of Sb, II:576
anion complexes, as toxic metal, of Se, II:1197–1198
I:175 of Ti, I:370
binding molecules, toxic animals and, II:1293
GSH and, I:178–179 humans and, II:1293–1294
introduction to, I:177 cell concentrations of, I:6
MTs and, I:177–178 cell signaling pathways and, II:594
summary on, I:179 As and, I:187–188
biogeochemical transport of, AP-1 and, I:186–187
I:426–430, I:427f Cd and, I:188–189
atmospheric, I:426–427 Co and, I:189–190
estuaries/freshwater and, Cr and, I:189
I:428–429 HIF-1 and, I:185–186
ocean as, I:428 introduction to, I:184
sediments and, I:429–430 MAPK and, I:185
speciation in water and, NF-AT and, I:186
I:427–428, I:427f NF-κB and, I:186
biological monitoring of, I:26–27 Ni and, I:190–191
biotransformation/distribution/ other metals and, I:191
transport of, I:58–60, I:58f–59f P13K/Akt and, I:185
calibration of, I:37–38 ROS and, I:184–185
carcinogenicity of, II:851, signal transduction pathways
II:1103–1105, II:1120, and, I:184–187
II:1359–1360 chemistry, I:21–22, I:21t
of As, I:8–9, I:173, I:593–594, commercial/industrial uses of, I:7
II:604–609, II:604t, II:608t compounds, I:4
animal models in, I:359–360 complexes or, I:19
epidemiological observations of, covalent/ionic bonds of, I:17–18
I:358–359 inorganic, I:18
evaluation of, I:360–361 metallic elements/metalloids as,
in vitro studies for, I:360 I:17–19
of Al, II:560 organometallic, I:4
of Be, I:8–9, I:364–365, II:646–648 oxidation number of, I:18
of Cd, I:8–9, II:696–698 compounds, carcinogenicity of,
animal models in, I:363 I:8–9
epidemiological observations of, As and, I:358–361
I:361–362 beryllium and, I:8–9, I:364–366,
evaluation of, I:363–364 II:646–648
in vitro studies, I:363 Cd and, I:361–364
of Co, I:368, II:758–759 Co and, I:368
i20
Metal(s) (Continued )
Cr and, I:355–358
Fe and, I:368–369, II:893–894
lead and, I:366–368
Mg and, I:369
Ni and, I:352–355
potential mechanism, I:370–372
principal, I:351–370
Pt and, I:369–370
Ti and, I:370, II:1294
conclusions on, I:41
containing biological molecules
Co, I:22
lead, I:22
metal-activated enzymes/
metalloenzymes as, I:22
metalloporphyrins as, I:21–22,
I:21t
MTs as, I:22
nonheme iron proteins as, I:22
definition of, I:16
detection methods for
AES as, I:33–34
AFS as, I:33
biosensors for monitoring metal
ions as, I:36
current, I:32–37
electrochemical, I:36
general aspects of, I:32
ICP-MS as, I:34–35
MS as, I:34–36
NAA as, I:37
particle characterization as,
I:36–37
spectrophotometry as, I:36
SSMS as, I:35
distribution of, I:45
in ecosystems, I:433–436
ecotoxicology of
accumulation/bioavailability/
elimination/uptake and,
I:430–431
aquatic food chains and, I:431
biological monitoring and,
I:439–440
biomarkers as HI in, I:438–439
defense against/storage of
metals and, I:431–433
individual, I:440–455, I:441f
methods, I:436–437
plant defense systems and,
I:432–433
sources of, I:425–426
element analysis/speciation/
metallomics and, I:22–23,
I:31–32, I:465
emissions of
into nature, I:425–426
to soil, I:426
Index
into water, I:426
epigeneticity, Cd and, I:183
epigenetics of
in development of cancer,
I:181–182
introduction to, I:180–181
metal compounds and,
I:182–184
Ni and, I:183–184
excretion of
gastrointestinal, I:60–61
mechanisms/pathways in,
I:60–63, I:62f
rate/biological half-time,
I:62–63
renal, I:45, I:61–62, I:62f
exposure to, I:45
through drinking water/food,
I:48–49
general aspects of, I:46–47
by inhalation, I:47–48
toxicology of, I:8
uses of critical organ concen-
tration in, I:69–70, I:70f
uses of indicator media for
estimation of, I:69–70, I:70f
fume, I:48
fume fever, II:779
genotoxic/mutagenic effects of
As/As compounds and, I:180
Cd compounds and, I:180
Cr compounds and, I:179–180
introduction to, I:179
Ni compounds and, I:179
health and, international
perspectives on, I:4–7
heavy, I:15–16
hemopoietic effects of, I:490
hepatic effects of metals, I:490
immunotoxicology of, II:945
autoimmunity and, I:391–392
dose-response considerations in,
I:380–381
Hg and, I:390–391
host-resistance challenge systems
and, I:381–382
hypersensitivity induced by,
I:383–384
hypersensitivity reactions caused
by, I:384–388
immunosuppression induced by,
I:381–382
introduction to, I:379–381
mechanisms in, I:380
nonspecific immunostimulation
induced by, I:390–391
other protein interactions and,
I:389–390
Pb and, I:389
protein interactions and,
I:388–389
xenobiotics and, I:392–393
interactions among, I:12
ions, properties of
formation of, I:19–20
hydrolysis and, I:20–21
as Lewis acids, I:20
redox potential of, I:20, I:20t
main group/transition, I:21
metabolism of, I:45
introduction to, I:45–46
metal carcinogenic interactions
As in, I:224
Fe in, I:225–226
lead in, I:226
Ni in, I:226–227
selenium in, I:218, I:227–229
Zn in, I:229–230
metal interactions, I:218–223
As and, I:218
Cd and, I:219–221, I:220f
Hg and, I:222–223
lead and, I:221–222
molybdenum-Cu-Zn and, I:223
thallium/potassium and, I:223
mixtures of
concern, I:230
direction of interaction among,
I:233
future needs/perspectives on,
I:234–235
HI, I:231
introduction to, I:230
mechanism for, I:233–234
similar, I:230–231
toxicological significance of, I:234
TTD and, I:231–232
WOE and, I:232–234, I:232t
nephrotoxicity of, I:164, I:165t
neurotoxic, I:5, I:8
non, I:16
periodic table of, I:16–17, I:17t
poisoning
children and, I:517–518
clinical effects of, I:488–493
diagnosis of, I:493–495
treatments for, I:495–503
quality assurance of, I:38–40
data reporting for, I:40
definitions of, I:39
elements of, I:40
error sources within, I:39–40
interlaboratory testing results
and, I:40
statistical considerations for,
I:40
radioactive, I:454–455
reference materials on, I:38–41

renal effects of, I:490–491
risk assessments of, I:436–439
characterization of, I:480–481
communication/management in,
I:481–484
dose assessment and, I:462–464
dose-effect/dose-response,
I:471–480, I:472f, I:476t, I:477f
exposure and, I:471–480
HI and, I:464–471, I:469f
introduction to, I:461–462
sampling/sample preparation of
air and, I:24–26
food and, I:24–26
general considerations for,
I:23–24
water and, I:24–26
separation techniques for
CE as, I:30
GC as, I:30
GE as, I:30–31
LC as, I:27–30, I:28f
solubility of, I:19
in tobacco smoke, I:48
toxic effects, prevention of
in general environments,
I:511–517, I:526–528
introduction on, I:508–509
principles of, I:509–510
in work environments, I:511–517,
I:511t
toxicity, I:245
of Arsenite, I:175
assessment/mixtures of,
I:230–232, I:231t
chronic clinical effects of,
I:490–493
prenatal exposure/develop-
mental effects of, I:414–417
toxicity/neonatal exposure/
developmental effects of,
I:417–418
As in, I:415–416
toxicokinetic models for
dose-effect/dose-response uses
of, I:63–69, I:64f–66f
multi-compartment, I:65f–66f,
I:66–69
one-compartment, I:64–66,
I:64f–65f
psychologically based, I:65f–66f,
I:66–69
toxicology, I:213
age and, I:215–217
alcohol and, I:215
alcohol/tobacco and, I:215
As and, I:242–247
Be and, I:247–248
biological monitoring and, I:11
Index
Cd and, I:248–249
Co and, I:249–250
conclusions on, I:259
dosimetry/toxicokinetics and,
I:11–12
drugs and, I:215–217
ecological/natural environ-
mental mobilization processes
and, I:10
gene-environment interactions
and, I:242–259
Hg and, I:255–258
human health effects and, I:7–9
industrial/technological uses
and, I:5
introduction to, I:213–214
lead and, I:250–254
Ni and, I:258
others factors in, I:214, I:217
Pt and, I:258–259
risk assessments for, I:12–13
sex and, I:215–217
specific metals in, I:242–259
tobacco and, I:215–217
transuranic, I:455
Metal fume. See Condensation
aerosols
Metallic elements, I:17–19
Metalloenzymes
Cu, I:22
Zn, I:22
Metalloids, I:10, I:17–19, I:22, I:222
Metallomics, I:22–23
Metallophytes, I:433
Metalloporphyrins, I:21–22, I:21t
Metallothioneins (MTs), I:22, I:431,
II:676–677
interactions of, I:219
toxic metal-binding molecules,
I:177–178
Metal neurotoxicity, I:306. See also
Neurotoxicology of metals.
cellular uptake, I:306–307
clinical effects and early signs,
I:304–305
intracellular sequestration and
transport, I:307
mitochondria effects, I:308
outcomes of metal exposure,
I:308–309
oxidative stress, I:307–308
Methoxyethylmercury compounds,
II:1063
Methyl (CH3), I:22
Methylation, I:10, I:56, I:56f, I:60,
I:448–449, II:592–593
Methylcobalamins, I:22
Methylcyclopentadienyl manganese
tricarbonyl. See MMT
i21
Methylisobutyl ketone (MIBK), I:33
Methylmercury (MeHg), I:132,
II:1019, II:1051–1054
in blood levels, I:11
in CNS, I:11, I:65–66, I:65f
cysteine, I:59–60, I:59f
dangers of, I:5
effects of, I:274–275
exposure to, I:222–223
as HI, I:509–510
secretion of, I:60–61
as toxic metal, I:174
Methylmercury-cysteine, I:59–60,
I:59f
Mexico, II:599
Mexico City Metropolitan Area
(MCMA), II:860–861
Mg. See Magnesium
MIBK. See Methylisobutylketone
Micellar electrokinetic capillary
chromatography (MECC), I:30
Microbial organisms, II:804
Microcirculation abnormalities, II:604
a1-Microglobulin (protein HC),
I:165t
β2-Microglobulin, I:165t
Microwave-induced plasma mass
spectrometry (MIP-MS), II:801
Mid-ocean ridge basalt (MORB),
II:859
Mines, I:6–7
Minimal risk level (MRL), I:231–232
MIP-MS. See Microwave-induced
plasma mass spectrometry
Mitochondria, II:891
Mitochondrial inhibition, II:593
Mitogen-activated protein kinase
(MAPK)
activation of, I:188
cell signaling pathways and, I:185
Mitogen-activated protein kinase
kinase 1 (MEKK 1), I:308
MMA. See Monomethylarsonic acid
MMAD. See Mass median
aerodynamic diameter
MMT (methylcyclopentadienyl
manganese tricarbonyl), I:522
Mn. See Manganese
MnO4-. See Permanganate ion
Mo. See Molybdenum
MOA. See Mode of action
Modeling
biological basis for, I:207–208, I:208t
of dose-effect, I:200–204, I:200f–202f
data, I:204–208, I:206f, I:208t
of dose-response, I:200–204,
I:200f–202f
data, I:204–208, I:206f, I:208t
Mode of action (MOA), I:462, I:466
i22
MoE. See Margin of exposure
Molecular mimicry, I:46
Molybdate, I:174
Molybdenum (Mo), I:7,
II:1304–1305
analytical methods/problems
associated with, II:1078
biological monitoring of,
II:1082–1083
chemical/physical properties of,
II:1077–1078
Cu-Zn metal-metal interactions, I:223
dietary recommendations/
requirements for, II:1082
dose-response relationships/effects
of, II:1083–1086
ecotoxicology of, I:451
environmental exposure/levels of
air/soil/water and, II:1079
daily intake/food and,
II:1078–1079
interactions with, II:1086
metabolism of
absorption/ingestion/
inhalation, II:1079–1080
biological half-time, II:1080–1081
distribution/excretion, II:1080
production/uses of, II:1078
Mongolia, II:599
Monomethylarsonic acid (MMA),
I:26–27, I:218
MORB. See Mid-ocean ridge basalt
(MORB)
Motor skills, I:306
Mosses, II:1350
MRL. See Minimal risk level
MS. See Mass spectrometry
MTs. See Metallothioneins
Mucociliary clearance, I:53, I:56f
Multicompartment models, I:66
for cadmium, I:67–68
toxicokinetic-toxicodynamic
modeling, I:68–69
Muscles, II:1042–1043
Mussel(s)
TBT and, I:453
watch, I:439–440
Mutagenicity, II:812, II:851,
II:945–946, II:1102–1103,
II:1359–1360
As and, II:610
of Co, II:756–758
of Cu, II:780
of Se, II:1197
of Ti, I:370
animals and, II:1294
humans and, II:1294
Myocardium, II:754–755
Mytilus edulis, I:431, I:439
Index
N language, I:305
NAA. See Neutron activation
analysis
NAC. See N-acetylcysteine
N-acetyl-b2-D-glucosaminidase
(NAG), I:165t
N-acetylcysteine (NAC), I:224–225
Nanoparticles, I:75–78
National Health and Nutrition
Examination Survey
(NHANES), I:143, I:216, I:304
National Institute for Environmental
Studies (NIES), I:38
National Institute for Occupational
Safety and Health (NIOSH),
I:483
National Institute for Standards
and Technology (NIST), I:38,
I:158–159
National Research Council Canada
(NRCC), I:38
Necrosis, I:309
Neonatal exposure, developmental
effects from metal toxicity,
I:417
As in, I:417
Pb in, I:418
Nephrotoxicity, I:164, I:165t
NEPSY-II. See NEuroPSYchological
Assessment II (NEPSY-II)
Nervous system, I:299–300, I:662,
II:694–695, II:755, II:808–809
autonomous, II:694–695
peripheral, II:694–695
Neural effects, II:599–600
Neurobehavioral testing, I:304–305
Neurological effects, II:663
Neuropathy, peripheral, I:491
NEuroPSYchological Assessment II
(NEPSY-II), I:305
Neuropsychological functions,
II:992–993
Neuropsychological tests, II:933–934.
See also Neurotoxicology of
metals.
Neurotoxicity
biomarkers of effects in, I:164–167
prevention of, I:495–496
Neurotoxicology of metals. See Metal
neurotoxicity
CNS development, I:301–306
academic skills, I:306
attention, I:305
clinical effects and early signs,
I:304–305
executive functions, I:306
human neurodevelopment, I:302f
infant neurodevelopment, I:305
IQ, I:305
learning and memory, I:305
motor skills, I:306
neonatal behavior, I:305
visuospatial skills, I:305
neurophysiology to neurotoxicology,
I:299
anatomical organization,
I:299–301, I:300t
clinical and preclinical neurotoxic
effects, I:301
central and peripheral, I:301
window of vulnerability, I:303
Neutron activation analysis (NAA),
I:37, II:856
categories of, I:37
method, I:37
New Caledonia, I:352–353
NFAT. See Nuclear factor of activated
T cell
NF-kB. See Nuclear transcription
factor
NHANES. See National Health and
Nutrition Examination Survey
Ni. See Nickel
Nickel (Ni), I:190–191
analytical methods/problems
associated with, II:1092
biological monitoring of,
II:1098–1099
carbonyl poisoning, II:1107
carcinogenicity of, I:8–9, I:94–95
animal models in, I:353–354
epidemiological observations of,
I:352–353
evaluation of, I:354–355
cell signaling pathways and, I:184
chemical/physical properties of,
II:1091–1092
compounds
as active inducers, I:190
genotoxic/mutagenic effects of,
I:179
ecotoxicology of, I:213
environmental exposure/levels of
air/soil/water and, II:1093–1094
food and, II:1094
working, II:1095–1096
epigeneticity of, I:166
female reproduction and, I:412
hypersensitivity and, I:240
metabolism of, II:1096
absorption, II:1096–1097
biological half-time, II:1097–1098
excretion, II:1097
metal toxicology and, I:155–156
in metal-metal carcinogenic
interactions, I:114
mutagenic effects of, I:371

neonatal exposure/developmental
effects from, I:417–418
prenatal exposure/developmental
effects of, I:414–417
production/uses of, II:1092–1093
in tobacco smoke, I:11
toxicology of, II:1099–1101
NIES. See National Institute for
Environmental Studies
NIOSH. See National Institute for
Occupational Safety and Health
NIST. See National Institute for
Standards and Technology
Nitrates (Ca(NO3)2), I:17–19
Nitrogen oxide (NO), I:10, I:165–166
NO. See Nitrogen oxide
NOAELs (no observed adverse effect
levels), I:168, II:610–611, II:949
approaches, I:168
as dose level, I:198–199
identification of, I:168
Noncardiovascular effects, of As,
II:598, II:599t
North America, I:286
North Sea, I:443
Norway, I:324, I:352
Nose, I:46–47
NRCC. See National Research
Council Canada
Nuclear factor of activated T cell
(NFAT), I:184
Nuclear magnetic resonance (NMR),
II:801
Nuclear transcription factor (NF-kB),
I:184
Number of person-years of
followup, I:266
Nutritional supplements, II:1374
O number of metal compounds, I:17
O2-. See Superoxide anion
Observational studies
ascertainment of, I:266–267
classification of, I:267–268, I:267t
Obstructive pulmonary disease,
II:556–557
Occupational environment, of Co,
I:368
Occupational exposure, II:551,
II:641–642, II:746
Occupational exposure limits
(OELs), II:746
Occupational Safety and Health
Administration (OSHA),
I:483, I:513
Ocean, biogeochemical transport of
metals in, I:426–430
ODC. See Ornithine decarboxylase
Index
OELs. See Occupational exposure
limits
OES. See Optical emission
spectrometry
Office of Pollution Prevention and
Toxics (OPPT), I:437
OH. See Hydroxyl radical
Oil, II:1350
Ophthalmic effects, II:601
Olfactory bulbs, II:747
Olfactory system, I:369, II:747
One-compartment model. See also
Multicompartment models
biomonitoring data conversion,
I:64–65
description, I:64
dose- response or dose-effect
relationships, I:65–66
toxicokinetics, I:64–65
OPPT. See Office of Pollution
Prevention and Toxics
Optical emission spectrometry
(OES), I:33
Oral contraceptives, I:215
Organic complexes, I:175
Organometallic compounds, I:19
Organotin compounds (OTCs), I:26
ecosystems and, I:27
separation of, I:29–30
uses of, I:27
Ornithine decarboxylase (ODC), I:228
OSHA. See Occupational Safety and
Health Administration
Osmium (Os), II:855–856
OTCs. See Organotin compounds
Ovalbumin (OVA), II:873
Oxaliplatin, I:258–259
Oxidation, I:542
arsenical reaction, I:358
of Hg, I:386
pyrite, I:426
Oxidative reactions, II:892
Oxidative stress, I:165–166, I:179,
I:307–308, I:370
Oxygen
dependent degradation, I:185–186
depletion, I:426
Oysters, I:443
P T cells/metal ions and, I:388–389
Packed cell volume (PCV), I:273
Paints, I:26, II:919
Palladium (Pd), I:388
analytical methods/problems
associated with, II:1114
chemical/physical properties of,
II:1113–1114
i23
dose-response relationships/effects
of, II:1118–1121
environmental exposure/levels of
ambient air/soil/water and,
II:1115–1116
daily intake/food and, II:1116
working, II:1116–1117
levels of, II:1118
metabolism of
absorption, II:1117
distribution/excretion,
II:1117–1118
prevention of, II:1121
production/uses of, II:1114–1115
Population critical concentration
(PCC), I:474–475
Parkinson’s disease, I:491, II:988
Particle(s)
deposition in lungs, I:52
deposition of, I:51–52
matters, I:515
respiratory system, clearance of,
I:52–56
size, I:51–52
translocation, I:55–56
Particulate matter (PM), I:50, I:51t
PASMC. See Pulmonary artery
smooth muscle cells
Pb. See Lead
PBPK modeling. See Physiologically
based pharmacokinetic
modeling
PBBs. See Polybrominated biphenyls
PCBs. See Polychlorinated biphenyls
PCC. See Population critical concen-
tration (PCC)
PCV. See Packed cell volume
Pd. See Palladium
PDK1. See Protein serine/threonine
kinase 3’-phosphoinositide-
dependent kinase 1
PE. See Performance error
PECs. See Predicted environmental
concentrations
D-penicillamine ( (CH3)2C(SH)CH
(NH2)CO2H), I:18–19
Penicillamine (cuprimine), I:60–61,
I:501, I:516
Peptides
LMW, I:431
MHC complex, I:389
Percent median absolute performance
error (MAPE %), I:144–145
Percent median performance error
(MPE %), I:144–145
Percent root median square
performance error (RMSPE %),
I:144–145
i24
Performance error (PE), I:144–145
Perfusion-rate-limited kinetics, I:142
Periodic table, of metals, I:16–17,
I:17t
Peripheral lung clearance, I:54–55.
See also Tracheobronchial
clearance
Peripheral nervous systems (PNS),
I:299–300
Peripheral vascular diseases,
II:602–603
Permanganate ion (MnO4-), I:17
Permeability-rate-limited kinetics,
I:142
Personal hygiene, I:513
Personal protective equipment, I:513
Peru, II:766
Pharmaceuticals, II:657
Pharmacokinetic/pharmacodynamic
relationships (PK/PD
relationships), I:142
Phosphate(s), I:33, II:906–907
absorption, II:906–907
binders, II:907
fertilizers, I:444
as toxic metals, I:174
Phosphatidylinositol-3 kinase
(P13K), I:185, I:191
Phosphatidylinositol-3,4,5-
triphosphate (PIP3), I:185
Phosphorylate phosphoinositides
(PIPs), I:185
Physiologically based
pharmacokinetic modeling
(PBPK modeling), I:141–143
and computational techniques and
tools, I:144
multiple PBPK models, I:141–142
toxicokinetic-toxicodynamic
modeling, I:68–69
Phytohemagglutinin, II:1167–1168
PIP3. See Phosphatidylinositol-3, 4,
5-triphosphate
PIPs. See Phosphorylate
phosphoinositides
PK/PD relationships. See
Pharmacokinetic/pharmaco-
dynamic relationships
Placenta, II:1050–1051
Plant(s), I:511–512, II:804, II:1373
Ba and, II:627
Be and, II:638
defense systems, ecotoxicology of
metals and, I:432–433
Se and, II:1179
Te and, II:1219
uptakes, I:444
Plasma, II:928–929, II:1375
Plastics, production of, I:9
Index
Platinum (Pt) Polychlorinated biphenyls (PCBs),
analytical methods/problems II:1034
associated with, II:1126–1127 Polymorphism
carcinogenicity of, I:369–370 genetic, I:12
chemical/physical properties of, of VDR, I:241
II:1125–1126 Polyunsaturated fatty acids (PUFAs),
dose-response relationships/effects II:892–893, II:1019–1020
of, II:1133–1138 Polyvinyl chloride, I:9
environmental exposure/levels of Population(s), I:453
food and, II:1129, II:1130t–1131t control, I:266
general, II:1127–1129, II: critical concentration, I:6, I:63
1130t–1131t effects/attributable risk in, I:267
working, II:1129, II:1130t–1131t general, II:1119–1120
female reproduction and, I:419 reference, I:266
group, I:388 at risk, I:521
metabolism of studies, II:1363
absorption/ingestion/inhalation, Population reference intakes (PRI),
II:1129–1132 I:286
biological fluids, II:1132–1133 Potassium
biological monitoring, II:1133 aluminum tetrafluoride, II:556
distribution/excretion/kinetics salts, I:388
and, II:1129–1132, II:1134t thallium metal-metal interactions
metal toxicology and, I:258–259 and, I:223
production/uses of, II:1127 Predicted environmental
risk assessments for, II:1138 concentrations (PECs), I:437
PM. See Particulate matter Predicted no effect level (PNEC),
PMN. See Premanufacture notice I:437
PNEC. See Predicted no effect level Pregnancies, I:216, I:400, II:897, II:926
PNS. See Peripheral nervous systems Premanufacture notice (PMN), I:437
(PNS) Prenatal exposure, developmental
Po. See Polonium effects of metal toxicity,
Point of departure (POD), I:414–417
I:143–144 Al and, I:416–417
Poisoning As and, I:415–416
As and Cd and, I:415
acute, II:613–614 Cr and, I:418
chronic, II:614 Hg and, I:416–417
Cd and Ni and, I:415–416
acute, II:686 Pb and, I:416–417
chronic, II:686–693, II:689t, V and, I:418
II:691f, II:693f Prevalence, I:266
enzyme, I:431 Prevention
Fe, II:894 of absorption, I:495–496
Hg, II:1030, II:1040–1043 of Cd, II:708
in fisherman, I:5 of Cu, II:781–782
in Japan, I:5, I:48–49 of metal toxic effects
in Sweden, I:5–6 in general environments, I:517
metal introduction on, I:508–509
children and, I:517–518 principles of, I:509–510
clinical effects of, I:488–493 in work environments, I:511t,
diagnosis of, I:493–495 I:517–518
treatments for, I:495–503 of neurotoxicity, I:526–528
Ni carbonyl, II:1107 of Pd, II:1121
V, II:1363 of Se, II:1202–1203
Zn, II:1381–1382 of Tl, II:1238
Polonium (Po), I:454–455 PRI. See Population reference intakes
Polybrominated biphenyls (PBBs), Prognosis
I:230 for Cd, II:708
Polycarbonates, I:25 for inorganic Pb, II:953

for organic Pb, II:956
for Se, II:1202–1203
for Te, II:1225–1226
for Tl, II:1238
Prosthetic devices, I:387–388
Prostate, II:697
Protein(s), II:890
binding, I:58–59, I:58f
DNA, I:241
frataxin, II:893–894
Fe, II:881, II:882t–883t
nonheme, I:22
heat shock, II:593–594
interactions
immunotoxicology of metals,
I:391
introduction to, I:389–390
T cells/metal ions and, I:388–389
seleno, I:222
stress, II:593–594
Protein HC. See a1-Microglobulin
Protein serine/threonine kinase
3’-phosphoinositide-
dependent kinase 1 (PDK1),
I:185
Provisional tolerable weekly intakes
(PTWI), I:283t, I:476, II:482–
483, II:705
Proxy variables, I:271–272
Pt. See Platinum
P13K. See Phosphatidylinositol-3
kinase
PTWI. See Provisional tolerable
weekly intakes
Puberty, onset of, I:408–409
PUFAs. See Polyunsaturated fatty acids
Pulmonary artery smooth muscle
cells (PASMC), I:189–190
Pulmonary fibrosis, I:490–491
Pulmonary functions, II:790–791
Pulmonary mechanisms, II:1325
Q II:1380–1381
QC. See Quality control
QSAR. See Quantitative structure
activity relationship
Quality assurance (QA)
BM reference materials for, I:158–159
of metals, I:38–39
data reporting for, I:40
definitions of, I:39
elements of, I:40
error sources within, I:39–40
interlaboratory testing results
and, I:40
statistical considerations for, I:40
procedures, I:40
Quality control (QC), I:39
Index
external, I:40
internal, I:40
Quantitative structure-activity
relationship (QSAR), I:437
Quantitative toxicological analysis.
See also Short-term and
long-term studies in animals.
benchmark dose, I:473–474
critical concentration, I:473
critical effect, I:472–473
critical organ, I:472–473
deterministic effects, I:472
DNEL and NAEL, I:473
dose effect, I:471–472
dose response, I:471–472
stochastic effects, I:473
R Respiratory tract, I:50, II:751
Radiation Emergency Assistance
Center/Training Site (REAC/
TS), II:1337
Radiochemical activation analysis
(RNAA), I:37
Rare earth elements (REEs), II:904
RBP. See Retinol-binding protein
RDA. See Recommended daily
allowance
Reactive oxygen species (ROS), I:191,
II:593, II:600–601
cell signaling pathways and,
I:184–185
formation, I:187
generation of, I:189
REAC/TS. See Radiation Emergency
Assistance Center/Training
Site
Recommended daily allowance
(RDA), I:285–286
Redox potential, I:20, I:20t, I:389
Redundancy, I:380
REEs. See Rare earth elements
Reference dose (Rfd), I:231, I:285,
Reference population. See Control
population
Reference materials (RMs), I:38–41
Renal cortex, II:680–681
Renal effects, II:1332–1334
of Hg, II:1041, II:1048–1049
of metals, I:490
Renal excretion, of metals, I:61–62,
I:62f
Renal mechanisms, II:1325–1327
Renal osteodystrophy, II:906
Renal toxicity biomarkers, I:164–165,
I:165t
Renal transport, II:1036–1039
Replicability, I:271
i25
Reproduction, II:792, II:1334–1335,
II:1360
As and, II:609
cancer and, II:952
fertility and, II:759
inorganic Pb and, II:946–949
male
Pb and, II:948–949
metal toxicity and, 7
Mn on, II:996–997
Ti and, II:1294
Reprotoxicity, II:759
Respiration, I:496
Respiratory effects
of As, II:600
of Co, II:751–753
Respiratory system, I:52–56,
I:489–491, I:574–575, II:575f
Response, I:272–274
Restrictive pulmonary disease,
II:555–556
Retinol-binding protein (RBP), I:165t
Reverse dosimetry, I:142–143
RfD. See Reference dose (RfD)
Rhodamine, II:566
Rhodium, I:388
Risk assessment
absorbed dose, I:463–464
applied/inhaled dose, I:463
cancer, I:209–212
daily intake, I:463
default factors in, I:476t
dose/concentration in critical organ
and critical target, I:464
use of biomarkers, I:464
of dose-effect, I:471–480, I:472f,
I:476t
of dose-response, I:471–480, I:472f,
I:476t
considerations for, I:209–212, I:210f
exposure and dose terminology,
I:462–463
to human health, I:461–462
for inorganic Pb, II:949–951
of metals, I:436–439
characterization of, I:480–481
communication/management in,
I:481–484
dose assessment and, I:462–464
dose-effect/dose-response,
I:471–480, I:472f, I:476t
exposure and, I:462–464
HI and, I:464–471, I:469f
introduction to, I:461–462
newer approaches to, I:480
for Pt, II:1138
steps in, I:462
time-consuming process, I:462
i26 Index

Risk characterization, I:480–481 SCOEL. See Scientific Committee on SEM. See Simultaneously extracted
Risk communication, I:484 Occupational Exposure Limits metals
RMs. See Reference materials Scotland, II:595t Semen, I:400–401, I:403
RNAA. See Radiochemical activation SCSA. See Sperm chromatin Semiconductor compounds
analysis structure assay analytical methods/problems
Rocks, I:442 SCTM. See Scientific Committee on associated with, II:787–788
Bi and, II:657 the Toxicology of Metals biological fluid levels of, II:790
Se and, II:1178 SD. See Standard deviation chemical/physical properties of,
U and, II:1316 Se. See Selenium II:787
ROS. See Reactive oxygen species Seafood, I:26–27 dose-response relationships/effects
Russia, II:1308 SEC. See Size exclusion chromatog- of, II:790–795
raphy environmental exposure/levels of,
Sediments, I:429, I:442, II:789, II:913 II:789
S Hg and, II:1021–1022 metabolism of
Safe Drinking Water Committee, Zn in, II:1371 biological half-time, II:790
I:207 Selenate, I:174 distribution/excretion, II:790
Safe Range of Population Mean Selenium (Se), I:12–13, I:294–295 ingestion/inhalation,
Intake (SRPMI), I:286, I:292 analytical methods/problems II:789–790
Saliva, II:924–925 associated with, II:1176–1177 production/uses of, II:788–789,
Salmonella, II:610 biological monitoring of, II:1189 II:788f
Salts, I:33 biomarkers of effects and, Serum, II:928–929
Al, II:551 II:1189–1190 Serum albumin, I:46
concentration of, I:440–441 biomarkers of exposure and, Sewage sludge, I:49
inorganic, I:57, I:222–223 II:1189 Sex, I:215–217
metal, I:57 chemical/physical properties of, Sheep red blood cell (SRBC), II:791
potassium, I:388 II:1176 Short-term and long-term studies in
sodium, I:388 compounds, I:29–30 animals, I:475
Sample(s) diagnosis/prevention/prognosis/ carcinogenesis and nonthreshold
hair, I:69 treatments for, II:1202–1203 effects, I:476–478
handling, I:23–24 dose-response relationships/effects threshold-type critical effects,
preparation of of I:475–476
air and, I:24–25 carcinogenicity and, SIDA. See Swedish International
food and, I:25–26 II:1197–1198 Development Cooperation
general considerations for, interactions with other metals, Agency
I:23–24 II:1199–1202 Signaling pathways
water and, I:25 mutagenicity and, II:1197 cell, II:1105–1106
spot, I:159 toxicity, acute/chronic and, AP-1 and, I:186–187
standardization, urine biological II:1187f, II:1190–1197 As and, I:187–188
monitoring and, I:159–161 ecotoxicology of, I:451 Cd and, I:188–189
techniques, I:515 environmental exposure/levels of Co and, I:189–190
Sampling ambient air/rocks/soil/water Cr and, I:189
duplicate, I:25–26 and, II:1178 HIF-1 and, I:185–186
kinetics, I:163–164 daily intake/food and, introduction to, I:184
preparation of II:1179–1180 MAPK and, I:185
air and, I:24–25 plants/tobacco and, metals and, I:184–187
food and, I:25–26 II:1178–1180 NF-AT and, I:186
general considerations for, working, II:1180 NF-κB and, I:186
I:23–24 kinetics of Ni and, I:190–191
water and, I:25 absorption, II:1184–1185 other metals and, I:191
sub, I:23–24 biological half-time, P13K/Akt and, I:185
Sb. See Antimony II:1188–1189 ROS and, I:184–185
SbH3. See Stibine gas biotransformation, II:1186–1187 signal transduction pathways
SCE. See Sister chromatid exchange distribution, II:1185–1186 and, I:184–187
Scientific Committee on excretion, II:1188 hypoxic, I:176–177
Occupational Exposure Limits metabolism/biological functions of, Silver (Ag), I:451–452
(SCOEL), I:483 II:1180–1181 analytical methods/problems
Scientific Committee on the in metal-metal carcinogenic associated with, II:1209
Toxicology of Metals (SCTM), interactions, I:218, I:227–229 chemical/physical properties of,
I:4, I:15, I:287–288 production/uses of, II:1177 II:1209

dose-response relationships/effects
of, II:1212–1214
environmental exposure/levels of
air/soil/water and, II:1210
daily intake/food and, II:1210
metabolism of
absorption/ingestion/inhalation,
II:1211
biological half-time, II:1211–1212
distribution/excretion, II:1211
production/uses of, II:1210
treatments for, II:1214
Simultaneously extracted metals
(SEM), I:434
Single crystal sapphire, II:858
Sister chromatid exchange (SCE), I:166
Size exclusion chromatography
(SEC), II:1327
Skeletal mechanisms, 1327
Skin, II:1024, II:1035
absorption through, I:463–464,
II:588, II:1094–1095
cancer, I:5, II:605, II:608t
contact, II:641–642, II:1256
effects, II:1100–1101
Al on, II:560
exposure, II:917
Sb/human, II:575
Smoking. See Tobacco
Sn. See Tin
SOD. See Superoxide dismutase
Sodium
chloride, I:33
salts, I:388
Sodium 2,3-dimercaptopropane
sulfonate (DMPS), I:492, I:499
Sodium 2,3-dimercaptopropane
sulfonate (DMSA), I:492, I:499
Soft tissue calcification, II:906
Soil, I:10, I:442, I:519, II:789,
II:803–804, II:913, II:1371
Ag and, II:1210
agricultural, I:444
As and, II:586
Ba and, II:626–627
Be and, II:637–638
Bi and, II:657
Cd and, II:672–673
Cd in, I:10
Co and, II:745–746
Cr and, II:719
Cu and, II:767
Hg and, II:1021–1022
In and, II:847
lanthanum environmental level,
II:905–906
metal emissions to, I:426,
I:432–433
Mn on, II:980–981
Index
Mo and, II:1079
Ni and, II:1093–1094
Pd and, II:1115–1116
Sb and, II:568–569
Se and, II:1178
Sn and, II:1253–1255
Te and, II:1219
Ti and, II:1289
U and, II:1316
V in, II:1349–1350
South Wales, I:352
Southeast Asia, I:449
Soy sauce, II:610–611
Spark source mass spectrometry
(SSMS), I:35, II:655–656,
II:800–801
Speciation
in biomarkers of exposure, I:163
element, I:22–23, I:31–32, I:465
of metals, I:15–44, I:17t, I:20t–21t,
I:28f
in water, biogeochemical transport
and, I:427–428, I:427f
Spectrophotometry, I:36
Sperm chromatin structure assay
(SCSA), I:401
Sprague-Dawley rat dams, I:228,
I:388
Sr. See Strontium
SRBC. See Sheep red blood cell
SRPMI. See Safe Range of
Population Mean Intake
SSMS. See Spark source mass
spectrometry
Standard deviation (SD), I:200, I:286,
II:1301
Stibine gas (SbH3), II:575
Stochastic effects, I:479
Stokes diameter, I:50
Stroke, I:313, II:603
Strontium (Sr), I:455
Substitutions, I:481–482
Succimer, I:500
Sucralfate, II:551
Sulfate mimics, I:174
Sulfur, I:10
dioxide, I:54
interactions with, II:1086
Sulfuric acid, I:54
Superoxide anion (O2-), I:184–185
Superoxide dismutase (SOD), I:22,
I:92–93, I:177, I:222, II:987–988
Sweat, I:217, II:924–925
Sweden, I:483, II:556
diets in, I:220
mercury poisoning in, I:5, I:10
Swedish International Development
Cooperation Agency (SIDA),
I:5–6
i27
T
Taiwan, I:243, I:345, I:359, II:585
Target-organ-toxicity dose (TTD),
I:231–232
TBT. See Tributyltin
TD. See Toxicodynamic modeling
TDI. See Total daily intake
TDS. See Total Diet Study (TDS)
Te. See Tellurium
TEA-Ch. See Test of Everyday
Attention for Children
(TEA-Ch)
Tellurium (Te), I:12–13
analytical methods/problems
associated with, II:1218
biological monitoring of,
II:1220–1221
chemical/physical properties of,
II:1218
diagnosis/prevention/treatments
for, II:1226
dose-response relationships/effects
of
animals and, II:1221
humans and, II:1221
systemic, II:1221–1225
environmental exposure/levels of
air/plants/soil/water and,
II:1219
daily intake/food and, II:1219
metabolism of
absorption/ingestion/inhalation,
II:1219–1220
biological half-time, II:1220
distribution/excretion, II:1220
production/uses of, II:1218–1219
standards for, II:1226
TEM. See Transmission electron
microscopy
Teratogenicity, II:851, II:1101
of Cu, II:780
of Ge, II:812
of Ti, I:370
animals and, II:1293
humans and, II:1293–1294
Terminology and Symbols,
Acceptance Sampling, I:40
Testes, I:229
Testicles, II:1042
Test of Everyday Attention for
Children (TEA-Ch), I:305
TETA. See Triethylene tetramine
Tetrachlorplatinite, I:388
Tetraethyllead. See Leaded
gasoline
Tetramethyltin (Me4Sn), I:30
TGFβ. See Transforming growth
factor beta
Thalassemias, I:493
i28
Thallium (Tl), I:12–13
analytical methods/problems
associated with, II:1230
biological monitoring of,
II:1233–1234
chemical/physical properties of,
II:1229–1230
diagnosis/prevention/treatments
for, II:1237–1238
dose-response relationships/effects
of animals, II:1234
of humans, II:1234–1236
environmental exposure/levels of,
II:1230–1231
metabolism of
absorption, II:1231–1232
biological half-time, II:1233
distribution/excretion,
II:1232–1233
potassium metal-metal interactions
and, I:223
production/uses of, II:1230
prognosis for, II:1238
Thimerosal, I:256, I:392
Thorium dioxide sol, II:851
Threshold effects, I:479
Thyroids, II:755, II:1042
Ti. See Titanium
Time to pregnancy (TTP), I:402
Tin (Sn)
analytical methods associated with,
II:1242–1247
chemical/physical properties of,
II:1242
compounds, I:12–13
environmental exposure/levels of
air/soil/water and, II:1253–1255
daily intake/food and,
II:1250–1253
working, II:1255
inorganic, I:452
absorption/ingestion/
inhalation/metabolism,
II:1255–1256
distribution/excretion/
metabolism, II:1256–1257
dose-response relationships/
effects of, II:1265–1268
levels, II:1263–1265
metabolism of inorganic
biological half-time, II:1257
distribution/excretion,
II:1256–1257
metabolism of organic
absorption/ingestion/
metabolism, II:1258–1260
biological half-time,
II:1261–1262
Index
distribution/excretion,
II:1260–1261
organo, II:1258–1263
organometallic, I:7
production/uses of, II:1247–1249
tributyl, I:26
Tissue(s)
calcified, II:924
damage mechanisms, II:891–894
hematopoietic, II:560
Titanium (Ti)
analytical methods/problems
associated with, II:1288
carcinogenicity/mutagenicity/
teratogenicity of, I:370
animals and, II:1293
humans and, II:1293–1294
chemical/physical properties of,
II:1287–1288
dose-response relationships/effects
of
animals, II:1291–1293
humans, II:1291–1294
environmental exposure/levels of
air/soil/water and, II:1289
daily intake/food and, II:1289
levels, II:1291
metabolism of
absorption, II:1290
biological half-time, II:1291
distribution/excretion,
II:1290–1291
production/uses of, II:1288–1289
on reproduction, II:1294
TK. See Toxicokinetic models
Tl. See Thallium
TNF. See Tumor necrosis factor
TNFα. See Tumor necrosis factor alfa
Tobacco, I:359, II:1095
As and, II:587
cadmium in, I:11
Cd and, II:673
Cr and, II:719
metal toxicology and, I:217
metals in, I:48
Sb and, II:569
Se and, II:1180
Tolerable weekly intake (TWI),
I:64–65, I:128, I:285
Total daily intake (TDI), I:143–144,
I:283t, I:285, I:482
Total Diet Study (TDS), II:868
Total suspended particles (TSP),
II:1164
Toxic action mechanisms, II:648–649
Toxicity
assessment/metal mixtures and,
I:230–232, I:231t
biomarkers, renal, I:164–167, I:165t
of Cr, II:738–739
definitions of, I:283t
gastrointestinal, II:896
lung, biomarkers of effects in,
I:165–166
mechanisms of, II:753
metabolism of As, II:593–595
metal
of As, I:242–247
of Arsenite, I:175
assessment/mixtures of,
I:230–232, I:231t
chronic clinical effects of,
I:490–493
on female reproduction,
I:412–414
introduction to, I:399–400
on male reproduction, I:403–408
prenatal exposure/develop-
mental effects of, I:414–417
risks associated with EMs, I:
281–283, I:284f, I:288f, I:291f
of Se, acute/chronic, II:1187f,
II:1190–1202
subclinical, I:521–522
Zn, II:1379–1382
Toxicodynamic modeling (TD),
I:68–69
Toxicokinetic models (TK), I:11–12
for metals
dose-effect/dose-response uses
of, I:63–69, I:64f–66f, I:68f
multi-compartment, I:66–69,
I:67f–68f
one-compartment, I:64–66,
I:64f–65f
psychologically based, I:66–69,
I:67f–68f
TD models, I:68–69
Toxicokinetic(s), I:142, II:954–955. See
also Metabolism.
of Cd, II:680–681
of Ge, II:800–801
of inorganic Pb, II:919–927, II:922f,
II:925f
of Mn
absorption/ingestion/inhalation,
II:982–984
distribution/excretion,
II:984–986
models, I:63
multicompartment models,
I:66–69
one-compartment model, I:64–66
physiologically based models,
I:66–69
of Pb, II:925–926

of organic Pb, II:954–955
of U, II:1318
absorption/ingestion/inhalation,
II:1318–1320
distribution/elimination/
excretion/metabolism,
II:1320–1322
of V
absorption/ingestion/inhalation,
II:1351–1352
biological half-time, II:
1353–1354
distribution/elimination,
II:1352–1353
Toxicology
metal, I:213
age and, I:215–218
alcohol/tobacco and, I:213–214
As and, I:242–247
beryllium and, I:247–248
biological monitoring and, I:11
Cd and, I:248–249
Co and, I:248–249
conclusions on, I:259
drugs and, I:215
ecological/natural environ-
mental mobilization processes
and, I:10
gene-environment interactions
and, I:239–242
Hg and, I:222–223
human health effects and, I:7–9
industrial/technological uses
and, I:3–4
introduction to, I:213–214
lead and, I:250–254
metabolism/toxicokinetics and,
I:11–12
Ni and, I:226–227
others factors in, I:215–217
Pt and, I:258–259
risk assessments for, I:12–13
sex and, I:215–217
specific metals in, I:242–259
of metals
biological monitoring and, I:11
ecological/natural environ-
mental mobilization processes
and, I:10
human health effects and, I:7–9
industrial/technological uses
and, I:9
metabolism/toxicokinetics and,
I:11–12
risk assessments for, I:12–13
routes of exposure in, I:10–11
TPA-responsive element (TRE),
I:186–187
Index i29
Tracheobronchial clearance, I:53–54 metabolism/uptakes of, I:452
Training, I:516 mussels and, I:453
Transferrin snails and, I:453
cellular iron acquisition from, Trien. See Triethylene tetramine
II:881–885, II:884f Triethylene tetramine (Trien; TETA),
iron export from, II:885 II:781
Transforming growth factor beta Triethyltin, II:1259
(TGFb), I:241–242 Trimethylantimony (Me3Sb), I:30
Transmission electron microscopy Trimethylbismuth (Me3Bi), I:30
(TEM), I:36–37 Trinitrophenyl, I:388–389
Transport Triphenyltin, II:1269–1270
of As, II:589 Tripropyltin, II:1269–1270
of Ba, II:628 TSP. See Total suspended particles
of Be, II:640–641 TTD. See Target-organ-toxicity dose
of Cd, II:676–679, II:676f, TTP. See Time to pregnancy
II:678f–679f Tubulin, II:1052
function, I:58–59 Tumor necrosis factor (TNF),
of metals, biogeochemical, I:241–242
I:426–430, I:427f Tumor necrosis factor alfa (TNFa),
atmospheric, I:426–427 I:241–242
estuaries/freshwater and, Tungsten (W)
I:428–429 analytical methods/problems
ocean as, I:428 associated with, II:1298
sediments and, I:429–430 biological monitoring of, II:1301
speciation in water and, chemical/physical properties of,
I:427–428, I:427f II:1297–1298
of metals into air, I:426 dose-response relationships/
of metals to biogeochemical effects of
estuaries, I:428–429 animals and, II:1301–1304
of Zn, II:1370–1371 humans and, II:1302–1304
TRE. See TPA-responsive element environmental exposure/levels of,
Treatment(s) II:1299
for Ag, II:1214 interactions of, II:1304–1305
for As metabolism of
acute poisoning, II:613–614 absorption, II:1300
chronic poisoning, II:614 biological half-time, II:1301
for Ba, II:632–633 distribution/excretion, II:1300
for Be, II:650–651 production/uses of, II:1298–1299
for Bi, II:663 TURA. See Toxic Use Reduction Act
for Cd, II:707–708 TWI. See Tolerable weekly intake
for Cu, II:781–782
for inorganic Pb, II:1237–1238
for metal poisoning, I:495–503 U
for Ni, II:1107 U. See Uranium
for organic Pb, II:956 Ukraine, II:1116, II:1350
for Se, II:1202–1203 UL. See Upper level of tolerable intake
for Te, II:1226 Ultraviolet (UV), I:30, I:229
for Tl, II:1237–1238 UNEP. See United Nations
trials for Ge, II:812–813 Environment Programme
for U, II:1337–1338 United Kingdom National External
water, II:554–555 Quality Assessment Service,
Trialkyltin compounds, II:1268 I:159
Tributyltin (TBT), I:27, II:1259–1260, United Nations Environment
II:1269–1270 Programme (UNEP), I:4, I:69
active mechanism for, I:453–454 3′ Untranslated regions (UTR),
adverse effects of, I:452–454 II:881–883
as antifouling agent, I:452 Upper level of tolerable intake (UL),
dispersal/use of, I:452 I:285
i30 Index

Upper respiratory tract, II:751 Vanadium (V) contaminated, I:5, I:10

Uptakes, I:430–431 analytical methods/problems Cr and, II:719
of Cr, II:720. See also Absorption associated with, II:1348–1349 Cu and, II:767
Uranium (U) biological monitoring of, drinking, I:10, I:40, II:916
active mechanisms of, II:1323–1327 II:1354–1355 average intake of, II:585
analytical methods associated with, chemical/physical properties of, committees, I:207
II:1309–1312, II:1310t II:1348 exposure to metals through,
biomarkers of exposure and, dose-response relationships/effects I:47–48, I:429–430
II:1335–1337, II:1336t of, II:1355–1363, II:1357t fresh, biogeochemical transport of
chemical/physical/radiological environmental exposure/levels of metals into, I:428–429
properties of, II:1308–1309, air/soil/water and, II:1349–1350 ground, I:10, I:135–136
II:1309t–1310t daily intake/food and, Hg and, II:833–838
dermal effects of, II:1329 II:1350–1351 In and, II:847
dose-response relationships/effects existence of, I:454 lanthanum environmental levels,
of, II:1327–1335 poisoning, II:1363 II:905–906
environmental exposure/levels of, production/uses of, II:1349 maintenance of, I:496
II:1314t toxicokinetics of Mn on, II:980
air/rocks/soil/water and, absorption/ingestion/ Mo and, II:1079–1080
II:1313–1317 inhalation/, II:1351–1354 Ni and, II:1093–1094
daily intake/food and, II:1315 biological half-time/, Pd and, II:1115–1116
production/uses of, II:1312–1313 II:1353–1354 sampling/sample preparation of,
as toxic, I:10, I:62 distribution/elimination/, I:25
toxicokinetics of, II:1318 II:1352–1354 Sb and, II:568–569
absorption/ingestion/inhalation, Vanadium pentoxide (V2O5), II:1348 Se and, II:1178
II:1318–1320 Vanadyl, II:1352 sea, I:454
distribution/elimination/ Vapors, absorption of, I:51 Sn and, II:1253–1255
excretion/metabolism, Vascular endothelial growth factor systems, I:519
II:1320–1322 (VEGF), I:127 Te and, II:1219
treatments for, II:1337–1338 VDR, polymorphism of, I:241 Ti and, II:1289
Urine, II:596, II:929–930, VEGF. See Vascular endothelial treatments, II:554–555
II:1031–1033, II:1375 growth factor U and, II:1315–1316
kidneys and, I:159 Ventilation V in, II:1349–1350
levels, II:552t general room, I:512 Weibull distribution, I:207–208
pH in, I:62 local exhaust, I:512 Weight-of-evidence method (WOE),
relative density of, I:160 VIEM. See Virtual Institute for I:232–234, I:232t–233t
sample standardization, biological Reference Materials West Bengal, I:10
monitoring, I:159–161 Vietnam, II:585–586 Whiskey, I:520
trace elements in, I:24 Virtual Institute for Reference WHO. See World Health
uses of, I:46 Materials (VIEM), I:38 Organization
U.S. Atomic Energy Commission, Visuospatial skills, I:305 Wildlife, I:450–451
II:639 Vitamin Wilson disease, I:240, II:777
U.S. Centers for Disease Control and B12, coenzymes, I:22 Window of vulnerability, I:303
Prevention (CDC), I:234 C, I:228 Wine, I:520
U.S. Environmental Protection D, I:220, II:944 WOE. See Weight-of-evidence method
Agency, I:5, I:285, I:483, II:1210 E, I:228 Women, I:216, I:402, I:408, I:411–412,
U.S. Food and Nutrition Board, I:285, V2O5. See Vanadium pentoxide II:897
I:292–293 Work
U.S. Institute of Medicine, I:292–293 environments
U.S. National Human Exposure W monitoring of, I:513–516
Assessment Survey, II:597 W. See Tungsten prevention of metals’ toxic effects
UTR. See 3′ Untranslated regions Water, I:46–47, I:443, II:789, II:803– in, I:511–517, I:511t
UV. See Ultraviolet 804, II:913, II:1371 place/air, I:167–168
Ag and, II:1210 World Health Organization (WHO),
As and, II:585–586 I:3, I:16, I:125, I:155–156
V Ba and, II:626–627 Environmental Health Criteria
V. See Vanadium Be and, II:637–638 Document on Principles and
Vanadate Bi and, II:657 Methods for Assessment of
albumin complex, I:31 Cd and, II:672–673 Risk From Essential Trace
as metal compounds, I:191 Co and, II:745–746 Elements, I:282

principles of, I:155–156
in Southeast Asia, I:10
Task Group Meeting on
Environmental Health Criteria
for Arsenic, I:5
X analytical methods associated with,
XAFS. See X-ray absorption fine
structure spectroscopy
XANES. See X-ray absorption near
edge structure
Xenobiotics
autoimmune diseases by
Cd, I:393
Hg, I:392–393
Pb, I:393
general considerations for, I:381
X-ray absorption fine structure
spectroscopy (XAFS), I:27
Index
X-ray absorption near edge structure
(XANES), I:36–37
Z hair, II:1375
Zambia, I:531–535
Zinc (Zn), I:174, I:1369
II:1370
biological monitoring of,
II:1374–1375
chemical/identity/physical
properties of, II:1374–1375
concentrations of, I:219–220
Cu-molybdenum metal-metal
interactions, I:223
deficiency, I:9, I:229, I:285, II:1379
effects evaluation of, II:1382
environmental distribution/
transformation/transport of,
II:1371
i31
environmental exposure/levels of,
II:1370–1371
essential metals and, I:21, I:174
in foods, II:1372t, II:1373–1374
human
exposure/levels of, II:1372–1374
nutriture, II:1375–1382, II:1378t,
II:1380t
metalloenzymes, I:22
metal-metal carcinogenic
interactions, I:219–221
oxide fume, II:1375, II:1381
poisoning, II:1381
serum, II:1375
supplementation, I:229
as toxic metal, I:174
toxicity, II:1379–1382
white blood cell, II:1375
Zn. See Zinc