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OCR for page 221
Index
A
Acidic aerosols, effects of, 18, 135-137
Additivity, 7, 54
assumptionsin cancer model, 193-198
in generalized model, 215-217
allow closes, 102-104, 195-198
and responses in interactions, 83, 100
and risks associated with individual
components, 180-182
in simple model, 215
Aerosols
acidic, effects of, 18, 135-137
collection procedures for, 72-73
Aflatoxin
bioactivity of, 50
effects in animals, 29
Air, ambient
benzo(a)pyrene in, 13
particulate matter in. See Particulate matter
in air
Air pollution, sulfur dioxide and particulate
matter in, 31, 133-137
Alcohol intake, smoking with, and oral
cancer, 6, 20, 32-33, 148-151
Aliphatic compounds, 79
Ambient exposure, variability in, 23
American Conference of Governmental
Industrial Hygienists, 72
Ames assay, for mutagen content of tobacco
smoke, 170-171
221
Analysis of mixtures, 78-89
requirements for, 80-81
separation methods for, 81, 82-87
spectroscopy and spectrometry in, 87-89
Animal studies, 6, 25-30
alcohol intake and cigarette smoking, 32-33
analysis of inhalation experiment, 211-215
asbestos exposure and smoking, 32, 144
chlorination byproducts in water, 33
coal-mine dust, 34, 160-161
coke-oven emissions, 33-34, 156- 157
complexity of agents affecting, 27-28
developmental toxicology, 202-207
fractional factorial design in, 57-58
hydrocarbon toxicity, 45
lead exposure, 31-32
limitations of, 28-30
in long-term exposures, 27
nonconcurrence with human experience,
30-34
radon daughters and cigarette smoke, 32,
141
screening for necrologic disorders, 45
in short-term exposures, 26-27
sulfur dioxide exposure, 27-28, 29, 31,
134-136
toxicokinetics in, 30
Antagonism, and interactions of components,
7, 83
Aquatic test systems, 56
Aqueous samples, collection of, 73-74
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222
Aromatic compounds, 79
Asbestos exposure, interaction with cigarette
smoke, 20, 29-30, 32, 143-148 Case studies
Ashford-Cobby model, 217, 218, 219
B
Battery approach to testing, 46
Benzene exposure, and cancer risk, 22
Benzo(a)pyrene
air temperature affecting, 67
in cigarette smoke, 146
asindicatorof exposure, 13
Bioassay
directed fractionations, 49-51
preparation of materials for, 77-78
Bioavailability
and exposure assessment, 14-16
physical state of substrate affecting, 15-16
Biologically effective dose, 7-8, 11
Blood pressure, lead exposure affecting,
31-32, 137-140
Bronchitis, from coal-mine dust, 34, 159
C
Cancer models, 185-201
additivity assumptions in, 193-198
and background tumor rate, 195
dose-response relationshipin, 192-193
exposure to multiple agents in, 186-188
and prediction of risk at low doses, 198-199
synergism effect in, 183-192
Cancer risk
assessment with comparative-potency
method, 47
from chlorination byproducts in water,
151-155
and initiation-promotion studies, 117- 118
recommendations for research in, 119- 120
in rubber industry, 22
Carbon monoxide
interaction with carbon dioxide, 174,
211-215
in tobacco smoke, 170
Carcinogens
benzo(a)pyrene, 13
fish sensitivity to, 56
identification of, 28-29
initiation-promotion studies of, 117
INDEX
and protective effect of micronutrients, 20
screening studies for, 44
cigarette-smoke toxicity, 168- 171
fire atmospheres, 172- 175
hexacarbonneuropathy, 176-178
Chemical
characterization of mixtures, 66, 79
search for causative agents, 51-52
Chemotherapy for cancer, maximal tolerable
doses in, 26
Chlorinated dibenzofurans, differential uptake
of, 15
Chlorination byproducts in water, 151-155
evaluation of risks from, 33
long-term exposure to, 19
Chloroform, interaction with chlordecone,
54-55
Chromatography, 82, 84-87
column, 84
gas, 88, 89
gel-permeation, 85
high-performance, liquid, 85, 86
high-resolution techniques in, 85-86
supercritical-fluid, 87
thin-layer, 85
Cigarette smoking. See Smoking
Classification of complex mixtures, 65-66
chemical, 66, 79
Cluster sampling, 69
Coal gasification, hazardous materials in,
128- 129
Coal-mine dust
constituents in, 129- 130
toxic effects of, 34, 157-161
Coal tar
exposure in animals, 33, 156
materials in, 127
Coke-oven emissions, 155-157
animal studies, 33-34
control of, 19
and lung cancer risk, 13
relative potency tests of, 47
Collection of samples, procedures in, 72-76
for aqueous materials, 73-74
for gases and aerosols, 72-73
for nonaqueous liquids, 74-75
for solids and sediments, 75-76
Combustion products, 127 129
Comparative-potency studies, 46-49,
106-108
Cox proportional hazards model, 210
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INDEX
D
Developmental toxicology, 202-207
dose-response models in, 204-206
statistical methods in, 202-204
trend test in, 206
Diethylnitrosamine exposure, and responses in
fish, 56
Diethylstilbestrol effects in animals, 29
Dinitropyrenes, bioactivity of, 50
Dioxins, in liquid or semisolid media, and
bioavailability, 15-16
Distillation products, 127-129
Dosage
biologically effective, 7-8, 11
for inhaled materials, 16-18
estimation with sampling, 12
exposure related to, 8, 11 - 18
maximal tolerated doses, 26, 112
prediction of low-dose risks, 115- 117
surrogates for, 12
and synergism, 7
Dose-response relationships, 11
in cancer model, 192-193
in developmental effects, 204-206
in interaction studies, 54-55, 100
Dump sites, hazardous chemicals in, 130
Duration of sampling, importance of, 67-68
E
Effect-search strategies, 52-53
Effects of complex mixtures
questions related to, 40-41
strategies related to, 42-49
Emphysema, from coal-mine dust, 34,
157-158
Empirical models, 121, 209-219
requirements for, 55-56
Experimental design for mixtures, 110- 119
and developmental-effects studies, 120- 121
empirical modeling in, 209-219
identification of toxic agents in, 111 - 113
for initiation-promotion studies, 117- 118
for predicting low-dose risks, 115- 117
response-surface analysis in, 113-115
for screening and low-dose extrapolation,
118-119
Exposure
assessment of
cost of, 25
and misclassifications, 12
223
complexity of, 18- 19
direct measurements of, 23
history of, 24
indicators of, 13-14
indirect measurements of, 23
inexact and incorrect measurements of, 25
multiple
carcinogenic agents in, 186- 188
interactive effects of, 20-22
relationship to dose, 8, 11 - 18
routes of, 66-67
and analysis of mixtures, 80
end bioavailability, 15
statistical issues in, 24-25
F
Fires, toxic agents in, 53
case study of, 172-175
Fish species, toxicity testing with, 56
Formaldehyde, and clearance rates for
particles in respiratory tract, 18
Fractional factorial design, for assessment of
substances, 57-58, 107-108, 119
Fractionations
bioassay-directed, 49-51
general considerations in, 79-82
methods in, 82-87
Fuels, hazardous chemicals in, 127-129
G
Gases, collection procedures for, 72-73
Gasification of coal, hazardous materials in,
128-129
Gasworkers, exposure to benzo(a)pyrene in,
13
Generalized linear models, 210-219
Global approach in testing of mixtures,
107-108
Grid patterns for sampling, 71
H
Haloalkanes, interaction with ketones, 54, 55
Hewlett-Plackett model, 217-219
Hexacarbon-neuropathy case, 44, 176-178
Hexobarbital activity, interspecies variations
in, 30
Hydrocarbons
boiling range and aromaticity of, 45 .
chemical search for components in, 52
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224
in cigarette-smoke condensate, 49
in coal tar, 127
comparative potency of, 48
in petroleum, 128
Hydrocyanic acid, interaction with carbon
monoxide, 174
Hypertension, and lead exposure, 31-32,
137-140
I
Identification of toxic agents, 111 - 113
Indicators of exposure, 13- 14
Inhaled materials
and estimation of effective dose, 16- 18
and particulate clearance affected by sulfur
dioxide, 133- 137
repetitive exposure to, 23
Initiation-promotion studies, designs for,
117-118
Interactions of components in mixtures, 6-7,
20-22
and dose-response curves, 54-55, 100
and generalized additive model, 215-217
mechanistic principles in, 55
and synergism effect in cancer model,
183-192
testing for, 109
International Agency for Research on Cancer
(IARC), 21, 28-29
International Commission on Radiological
Protection, 16, 24-25
International Standards Organization, 72
Interpretation of results, and comparative
evaluation, 106-108
Interspecies variability in susceptibility to
toxicants, 25-30
K
Ketones, interaction with haloalkanes, 54, 55
L
Lead exposure
and hypertension, 31-32, 137- 140
and interspecies variations in absorption, 30
Liquid-liquid partitioning, 81, 82, 83-84
Liquids, nonaqueous, collection of samples,
74-75
Litter effect, in developmental toxicology, 202
INDEX
Long-term exposures, 18- 19
animal studies of, 27
Low-dose exposure
and additivity of excess risks, 195-198
prediction of risk in, 115-117, 198-200
Lungs
cancer of
and asbestos exposure in smokers, 20,
29-30, 32, 143-148
and exposure to benzo(a)pyrene, 13
and radon exposure in smokers, 20,
29-30, 32, 140-143
risk assessment with comparative-potency
method, 47
smoking associated with, 13, 32
in uranium miners, 142-143
deposition of airborne particles in, 16-18
disease from coal dust, 34, 157-161
M
Mathematical models, 102- 105
in comparative-potency testing, 47
for estimation of exposure, 24-25
Matrix testing, 45-46
Meteorologic considerations in sampling, 67
Micronutrients, protective effects of, 20
Miners
coal dust exposure in, 34, 157-161
radon exposure and smoking in, 32,
142- 143
Model-driven strategies, 53-56
Models in toxicology, 100- 101
animal. See Animal studies
cancer, 185-201
dose-extrapolation, 105-106
dose-response, 102-105
empirical, 121, 209-219
requirements for, 55-56
mathematical, 24-25, 47, 102-105
multistage, 180
for cancer risk, 186-201
for two materiels, 104
pharmacokinetic, 108-110, 121-122
quasibiologic, 217-219
Mortality data from surveys of occupations
and industries, 21
Multiple exposures, interactive effects of,
20-22
Multistage models, 180
for cancer risk, 186-201
for two materiels, 104
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INDEX
Multistage sampling, 69
Mutagens in tobacco smoke, 170-171
N
National Cancer Institute, 44
National Research Council, 19, 20, 23, 28, 29
Neuropathy, hexacarbon, 44-45, 176- 178
Newark soil samples, 14- 15
Nitrogen dioxide
asindicatorofexposure, 14
toxic effects of, 27
Nitroparaffins, chemical search for
components in, 52
Nitrosamines, in tobacco smoke, 170
Nutrition
and ingestion exposures from food, 23
and lead exposure, 137-140
and protective effects of micronutrients, 20
o
Oil shale, constituents in, 128, 130
Oral cancer risk, alcohol intake and smoking
in, 6, 20, 32-33, 148-151
Organometallic compounds, 79
Origins of complex mixtures, 127-131
Ozone
and clearance rates for particles in
respiratory tract, 18
as indicator of exposure, 14
p
Pairing of data bases, 51
Particulate matter in air
active agents in, 134
collection procedures for, 72-73
and estimation of effective dose, 16- 18
as indicator of exposure, 14
and sulfur dioxide, 31, 133- 137
temperature affecting, 67
Petroleum fractions, biologic activity of, 128
Pharmacokinetic models, 108- 110, 121 - 122
Physical characteristics of mixtures, 66
Pneumoconiosis, coal-workers, 34, 157- 158
Polychlorinated biphenyls
bioactivity of, 50
in liquid or semisolid media, and
bioavailability, 15-16
soil binding of, 15
225
Polyurethane foam, thermal degradation
products of, 51, 129, 173
Population groups, complexity of, 20
Potency of compounds, comparative studies
of, 46-49, 106-108
Predictions
and approach in testing mixtures, 39-40,
41-42
and comparative potencies of similar
substances, 106-107
and designs for low-dose extrapolation
115-117
in interaction studies, 58-59
in low-dose exposure, 198-200
and nonconcurrence between human and
animal responses, 30-34
and risks associated with individual
components, 180- 182
strategies related to, 53-56
unexpected results in, 109
and value of animal studies, 25-30
Pregnancy, and developmental toxicology,
202-207
Probability sampling, 68-69
Q
Quality assurance, and sample integrity, 24,
78
Quasibiologic models, 217-219
Questions in testing
related to causative agents, 41
related to effects, 40-41
related to predictability, 39-40, 41-42
related to strategies, 58-59
R
Radiation exposure
and skin cancer in smokers, 143
variations in, 19
Radon exposure, interaction with cigarette
smoke, 20, 29-30, 32, 140-143
Random sampling, 68-71
Recommendations for research, 119-123
Respiratory tract, deposition of airborne
particles in, 16- 18
Response-surface designs, 113- 115
Roofers, exposure to benzo(a)pyrene in, 13
Roofing tar, relative potency tests of, 47
Rubber industry, cancer risk in, 22
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226
S
Sampling, 66-78
cluster, 69
collection procedure in 72-76
9
collection strategy in, 66-71
for close estimation, 12
grid patterns, 71
meteorologic considerations in, 67
multistage, 69
and preparation of materials for assay,
77-78
probability, 68-69
quality assurance in, 24, 78
random, 68-71
and routes of exposure, 66-67
spatial considerations in, 68-71
and storage of samples, 76-77
stratified, 69
systematic, 69-71
temporal factors in, 67-68
Screening studies, 44-45
and designs for low-dose extrapolation,
118-119
Seasonal considerations in sampling, 67
Sediments, collection of samples from, 75-76
Separation of mixture constituents, 81, 82-87
chromatography in, 82, 84-87
liquid-liquid partitioning in, 81, 82, 83-84
Short-term exposures, 18
animal studies, 26-27
Silica dust, and clearance rates for particles in
respiratory tract, 18
Simplex-centroid design, in surface analysis,
114
Simplex-lattice design, in surface analysis,
114
Skin
absorption of materials in repetitive
exposures, 23
cancer of, and effects of smoking and
radiation, 143
Smoking
alcohol intake with, and oral cancer, 6, 20,
32-33, 148-151
animal studies of, 27
and asbestos exposure, 20, 29-30, 32,
143- 148
and benzo(a)pyrene exposure, 13
and biologically active compounds in
smoke, 28, 129, 170
INDEX
case study of, 168-171
and clearance rates for particles in
respiratory tract, 18
and exposure to toxic ingredients, 19
fractionation of smoke condensate, 49
and radon exposure, 20, 29-30, 32,
140- 143
relative potency tests of, 47
and skin cancer from radiation, 143
Soil samples
collection of, 75
2,3,7,8-tetrachlorodibenzo-p-dioxin in,
14-15
Solid materials, collection of samples in,
75-76
Solvents
for elusion of substances from water, 74
for extraction of materials from samples,
75, 82
in preparation of materials for assay, 77
Soots, comparative-potency studies of, 47
Spatial considerations in sampling, 68-71
Spectroscopy and spectrometry, 87-89
Statistical methods
in developmental toxicology, 202-204
in quantitation of exposure, 24-25
Storage of collected samples, 76-77
Stratified random sampling, 69
Sulfur dioxide
in animal studies, 27-28, 29, 31, 134-136
as indicator of exposure, 14
and particulate matter in air, 31, 133-137
Sulfuric acid, and clearance rates for particles
in respiratory tract, 18
Surface analysis, designs used in, 114
Surveys of occupations and industries,
mortality data in, 21
Synergism, 7
in cancer model, 183- 192
Systematic sampling, 69-71
T
Temporal considerations in sampling, 67-68
Teratologic effects of chemical mixtures,
202-207
Testing
aquatic systems in, 56
battery approach in, 46
bioassay-directed fractionation in, 49-51
bioassay identification in, 53
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INDEX
chemical search in, 51-52
choice of end points in, 41, lot
in developmental toxicology, 206-207
comparative-potency approach in, 46-49
complexity of mixture affecting, 57-58
driving forces in, 58
effect search in, 52-53
empirical models in, 55-56
fractional factorial design in, 57-58,
107-108, 119
global approach in, 107-108
interaction studies in, 54-55
matrix, 45-46
mechanistic studies in, 55
pairing of data bases in, 51
recommendations for, 122- 123
screening studies in, 44-45
strategies in, 42-56
formulation of, 59
integration of, 56-60
related to causative agents, 49-53
related to effects, 42-49
related to predictability and models,
53-56
related to questions and problems, 58-59
structuring of questions in, 40-42
summing of component toxicities in, 53-55
tier, 43 44
2,3,7,8-Tetrachlorodibenzo-p-dioxin in soil
samples, 14-15
Tier testing programs, 43 44
Time course in sampling, importance of, 67
Times Beach soil samples, 14-15
227
Tobacco smoke. See Smoking
Toxicokinetics, interspecies variations in, 30
Trend test, in developmental toxicology, 206
Trihalomethanes, in water, 33, 151-155
U
United States Environmental Protection
Agency, 14, 17, 72, 76
Uranium miners, and lung cancer in smokers,
142
V
Vegetable materials, pyrolysis products of,
129
Vinyl chloride
effects in animals, 29
thermal degradation products of, 129
in tobacco smoke, 170
W
Wastes, hazardous, 130
Water
activated-carbon filtration of, 19
chlorination byproducts in, 151 - 155
evaluation of risks from, 33
long-term exposure to, 19
collection of samples, 73-74
extraction from samples, 74, 75
hazardous chemicals in, 130-131
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Representative terms from entire chapter:
animal studies
