Assessment and Management of Chemical Risks - ACS Publications

Author Index

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Brown, Charles C , 57 Crouch, E. A. C , 97 Hoerger, Fred, 147 Hutt, Peter Barton, 83 Menzel, Daniel Β., 23 Morgan, M. Granger, 113 Nelson, Norton, 13

Rodricks, Joseph V., 3 Smolko, E l a i n e D., 23 Snyder, Robert, 37 T a r d i f f , Robert G., 3 Wilson, Richard, 97 Wodicka, V i r g i l 0., 131 Zentner, Rene D., 161 1

Subject Index A Acceptable d a i l y intake (ADI), 6 Accum, Frederick, c l a s s i c t r e a t i s e on a d u l t e r a t i o n s of food and drugs, 85 Aerosols, p r e d i c t i o n of the d e p o s i t i o n i n lung, 26 American Conference of Governmental Industrial Hygienists, r o l e i n f o r m a l i z i n g r i s k assessments, 148 American regulatory agencies and c o s t b e n e f i t a n a l y s i s , 162 American Society f o r Testing Materials , role i n formalizing r i s k assessments, 148 Antagonism competitive, dose-response graphic representa t i o n , 44,46f,47 noncompetitive, dose-response graphic representa t i o n , 44,46f,47 Β B a c t e r i a l revertant t e s t s , 21 as screen f o r mutagenic agents, 17 Bioassays accuracy i n t e s t i n g , problems, 39 data e x t r a p o l a t i o n , problems, 39 with i s o l a t e d enzymes, 41 median l e t h a l dose, 39 with organ systems, 39 with whole animals, 39 Bioassay systems, 39-41 B i o l o g i e s Act of 1902, 85 C Cancer dose-response e x t r a p o l a t i o n , use, 137 e x t r a p o l a t i o n i n small segments o f population, problems, 52,53f r i s k s , 106-9 safety f a c t o r approach t o s t u d i e s , 135

Carcinogens l o g - l o g transformation t o evaluate l e t h a l i t y , 50,51f m u l t i c e l l theory f o r e x t r a p o l a t i o n , 64 multistage theory f o r e x t r a p o l a t i o n , 63 no-threshold assumption, 69 nontoxic and noncarcinogenic i n o r i g i n a l form, 30 r e a c t i v e intermediates, 30-32 threshold v a r i a t i o n s , 68 Carcinogenesis, multistage theory, 75-76 C a r c i n o g e n i c i t y , o x i d a t i v e metabolism of xenobiotic compounds by man, as major determinant, 33 Chemicals f a c t o r s c o n t r i b u t i n g t o increased focus on r i s k s associated w i t h , 148 sources of exposure, 131 Chemical exposure end e f f e c t of t o x i c chemical on mammalian organism, 17,l8f entry of t o x i c chemical i n t o human body, 17 procedure to determine e f f e c t , 19 Chemical industry a n t i c i p a t i o n of regulatory d e c i s i o n s when developing new product, 58-59 major growth period 1945-1970, 147-8 r i s k assessment formalized by cor porate a c t i o n s , 148 Chemical Industry I n s t i t u t e o f Toxicology, 156 Chemical Manufacturers A s s o c i a t i o n c o s t - b e n e f i t a n a l y s i s , p o s i t i o n , 170 c o s t - e f f e c t i v e n e s s requirement o f Executive Order 12991, support, 171 regulatory impact analyses, p o s i t i o n , 170 r i s k assessment, importance of peer review, 171 Clark, A. J . , necessity f o r quan t i f i c a t i o n of b i o l o g i c a l data, 38

177 Rodricks and Tardiff; Assessment and Management of Chemical Risks ACS Symposium Series; American Chemical Society: Washington, DC, 1984.

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Clean A i r Act, 92,163 Clean Drinking Water Act, 149 Color A d d i t i v e s Amendment of 1960, 88 Comprehensive Environmental Response, Compensation and L i a b i l i t y Act of 1980, 163 Consumer Product Safety Act of 1972, 89,163 Corporate c o n s i d e r a t i o n s , i n t e r r e l a t i o n s h i p of r i s k assessment w i t h , 151-52 Corporate d e c i s i o n s , based on r i s k assessment, 150-52 Corporate d e c i s i o n making and r i s k assessment, 147-60 Corporate p o l i c i e s on r i s k determination, 151 Corporate r i s k assessment process, major p r i n c i p l e s , 149-50 Cost-benefit a n a l y s i s and American r e g u l a t o r y agencies, 162 as a n a l y t i c a l t o o l f o r e v a l u a t i n g major p u b l i c sector p r o j e c t s , 162 application to regulatory d e c i s i o n s , 163 chemical i n d u s t r y p o s i t i o n , 169-71 Chemical Manufacturers A s s o c i a t i o n , p o s i t i o n , 170 and executive orders, 163-64 and Regulatory Impact A n a l y s i s , 168 Senator Robert T. S t a f f o r d opposit i o n t o use I n environmental i s s u e s , 169 stages, 163 used by f e d e r a l agencies i n developi n g and i s s u i n g r e g u l a t i o n s , 167 Cotton Dust d e c i s i o n , Supreme Court 1981, 169 D Delaney Amendment, 158 Delaney Clause, 91 DEMOS, software system d e s c r i p t i o n , 121-22 r e w r i t t e n as PASCAL, 121-22 Dose-response bloassays with i s o l a t e d enzymes, 41 median l e t h a l dose, 39 most important e n t i t y , 39-41 with organ systems, 40 problems of accuracy i n t e s t i n g , 39 problems of data e x t r a p o l a t i o n , 39 w i t h whole animals, 39 curves, modes of expression, 38 d e f i n i t i o n , 59

Dose-response—Continued d i f f e r e n c e , v i r t u a l l y safe dose estimated f o r commonly used models, 71 extrapolation c h a r a c t e r i s t i c s of more commonly used models, 70 use of incremental responses, controversy, 54 graphic r e p r e s e n t a t i o n , 38 c a l c u l a t i o n of d i s s o c i a t i o n constant, 43 competitive antagonism, 44,46f,47 competitive antagonism, double r e c i p r o c a l p l o t , 45f double r e c i p r o c a l p l o t i n study of enzymatic r e a c t i o n s , 44 double r e c i p r o c a l p l o t , 45f example of Incremental curve, 42f l o g , 47 log-dose-probit p l o t , 53f log-dose-response, as a frequency d i s t r i b u t i o n , 51f log-dose-response curve, 48f l o g - l o g transformation, 50,51f l o g - p r o b i t p l o t , l e t h a l i t y of three chemicals, 52,53f mathematical equations, 43 Michaelis-Menton equation, 43,44 noncompetitive antagonism, 44,46f,47 normal equivalent d e v i a t i o n , 50 problem of determining responses by a s m a l l segment of population, 52 semllog-dose-response curve, 47,48f t e s t i n g , 4l,42f mathematical models, 59 r e l a t i o n s h i p s of more commonly used models, 70f,71f,72 t h r e s h o l d , d e f i n i t i o n , 38 v i r t u a l l y safe dose, v a r i a t i o n due t o l i m i t e d number of animals at each dose l e v e l , 72,74 Dose-response e v a l u a t i o n , 9 Dose-response e x t r a p o l a t i o n a l t e r n a t i v e method of converting f i n d i n g s t o man, 138,143 curves, 136 d i f f e r e n c e s i n r e s u l t s due t o choice of mathematical model, 138 problem of conversion of f i n d i n g s t o man, 138 t r a d i t i o n a l method of converting f i n d i n g s t o man, 138,143 Dose-response models, d i s c r i m i n a t i o n among, 69-76 Dose-response r e l a t i o n s h i p basic concepts, 37-55

Rodricks and Tardiff; Assessment and Management of Chemical Risks ACS Symposium Series; American Chemical Society: Washington, DC, 1984.

179

INDEX

Dose-response r e l a t i o n s h i p — C o n t i n u e d over range of observable and extrapolated response r a t e s f o r l o g normal, l o g l o g i s t i c , s i n g l e - h i t models, compar- i s o n s , 69 Dupuit, J u l e s , "On the Measurement of the u t i l i t y of P u b l i c Works", 162

Extrapolation—Continued gas and particle deposition i n the nasopharyngeal region of the respiratory tract, 26 high to low dose, 9 in animals, current s t a t i s t i c a l methods, 57,58 characteristics more commonly used dose-response models, 70 comparison of log-normal and logΕ logistic models, 63 dose-response function P(D), 58 Environmental and h e a l t h technology, hit theory, 63 log-logistic function model, advances i n 1970s, 148 tolerance frequency Environmental P r o t e c t i o n Agency, distribution, 62-63 generic r e g u l a t o r y p o l i c i e s , 159 log-normal, or probit, model, Executive orders tolerance frequency and c o s t - b e n e f i t a n a l y s i s , 163-64 distribution, 60,62 1981 executive order e s t a b l i s h i n g mechanistic models, 63-64 Task Force on Regulatory multihit model, 63 R e l i e f , 167 natural responsiveness Regulatory Impact A n a l y s i s s p e c i f i e d adjustments, 66-69 i n Section 3 of 1981 Executive pharmokinetic models, 64-65 Order, 167 problems, 9 Executive Order 12291, 167,168,171 single-hit model, 63 See Also Executive orders sources of uncertainty, 77 Chemical Manufacturers A s s o c i a t i o n virtually safe dose, support f o r c o s t - e f f e c t i v e n e s s definition, 58 requirement, 171 hypothetical tolerance frequency exemption of independent r e g u l a t o r y agencies, 169 distribution, 60,6lf Expected value o f i n c l u d i n g uncer importance of quantifying t a i n t y (EVIU) i n r i s k assess threshold, 68 ment , 117 interspecies, 23-35 Extrapolation Interspecies morphological differences, 24-26 i n animals, high t o low dose, 57-79 lung, similarities and dis a p p l i c a t i o n of pharmacokinetic similarities between human and modeling, 27 animal, 24 of chemical carcinogens from animals mathematical expression, 60 to humans, 19 mathematical models, comparison various, 137,138 high t o low dose e x t r a p o l a t i o n f o r pharmokinetic models, s i x dose response models, 73f characterizations, 27 log l o g i s t i c dose response models polymorphic xenobiotic compound assuming independent and metabolism in animals and a d d i t i v e background, 67f man, 30-32 dose-response quantitative and qualitative converting f i n d i n g s t o man, t r a d i relationship between test t i o n a l and a l t e r n a t i v e species and humans, 19 methods, 138,143 quantitative morphometric studies of problem of conversion of f i n d i n g s the human and animal to man, 138 lung, 24,25f of dose-response curve relationship between tolerance d i f f e r e n c e s i n r e s u l t s due t o distribution and dose-response choice o f mathematical curve, 61f model, 138 sample organizing scheme, 19,20f t o low doses, mathematical straight-line approach, 54 models, 137 threshold, definition, 68 dose-response mathematical models tolerance distribution models, 60-63 quantal response, 59 from toxicity tests, 15 q u a n t i t a t i v e response, 59 use of kinetic modeling, 33 time t o response, 59


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ASSESSMENT AND

F Federal Environmental P e s t i c i d e Control Act of 1972, 89 Federal Food and Drugs Act of 1906, 85 Federal Food, Drug, and Cosmetic Act of 1938, 87,88 Federal Interagency Testing Committee, 156 Federal Meat Inspection Act of 1906, 85 Federal regulatory agencies, a l t e r n a t i v e methods of r e g u l a t o r y c o n t r o l , 171 Federal r e g u l a t o r y s t a t u t e s a d m i n i s t r a t i v e exemptions, 91,92 b e n e f i t and cost i s s u e s , 90 broad i n t e r p r e t a t i o n of s t a t u t e language, 87-88,91-92 c l a s s e s of safety r i s k standards, 87-91 differences i n interpretation depending on f e d e r a l agency, 92 e v o l u t i o n of i n t e r p r e t a t i o n , 87-88 h i s t o r i c a l background, 84 l e g a l considerations i n r i s k assessment, 83-95 r e g u l a t o r y c o n t r o l mechanisms, 86 s a f e t y - r i s k standards, 86 Food A d d i t i v e Amendments, 92 Food and Drug Administration generic regulatory p o l i c i e s , 159 procedure used i n evaluating food a d d i t i v e s and contaminants, 134 role i n formalizing r i s k assessments, 148 Food Safety C o u n c i l , S c i e n t i f i c Committee, 131,132,144 comparison of mathematical models used i n e x t r a p o l a t i o n , 137 development of d e c i s i o n t r e e , 132 report on t o x i c response data, 70 Food, Drug and Cosmetic Act of 1958, 134 Food evaluating the safety of components, 131 g e n e r a l l y recognized as safe (GRAS), food a d d i t i v e , 136 use of d i r e c t a d d i t i v e s , few authorized, 136 Formaldehyde i n h a l a t i o n s t u d i e s , 26 and nasal tumors, 26 G Government r e g u l a t i o n s , p u b l i c perception, 164-66

M A N A G E M E N T OF C H E M I C A L RISKS

Government r e g u l a t i o n of c h e m i c a l s — See Federal r e g u l a t o r y s t a t u t e s Government r e g u l a t i o n of h e a l t h and s a f e t y , h i s t o r i c a l s t a t u t e s , 84-86 H Hazard index, c o n s t r u c t i o n , 109,110t Health and environmental technology, advances i n 1970s, 148 High to low dose, e x t r a p o l a t i o n i n animals, 57-79 Himmelstein and Lutz, accurate p r e d i c t i o n s of e f f e c t s on man with models b u i l t on p h y s i c o l o g i c a l pharmacokinetic, 27 I Industry, chemical, p o s i t i o n on c o s t b e n e f i t a n a l y s i s , 169-71 Industry perspectives on r e g u l a t o r y impact a n a l y s i s , 161-73 I n h a l a t i o n studies of formaldehyde, 26 I n h a l a t i o n t o x i c a n t , d i f f i c u l t y of d i r e c t measurement, 27 Inhalation toxicology experiments, s e n s i t i v i t y to anatomi c a l d i f f e r e n c e s , 24 a p p l i c a t i o n of mathematical models, 27-30 I n s e c t i c i d e s Act of 1910, The, 86 Interspecies e x t r a p o l a t i o n , 23-35 lung, 24 polymorphic xenobiotic compound metabolism, 30-32 q u a n t i t a t i v e morphometric studies of the lung, 24,25f use of k i n e t i c modeling, 33 J J o i n t Experts Committee on Food Additives (FAO/WHO), procedure used i n e v a l u a t i n g food a d d i t i v e s and contaminants, 134 Κ K i n e t i c modeling, using the physiological-anatomical approach, 33 L LD50—See Median l e t h a l dose, 39 Legal considerations i n r i s k assess ment under f e d e r a l regulatory s t a t u t e s , 83-95


INDEX

181

Lexington M i l l Decision, d e f i n i t i v e i n t e r p r e t a t i o n of various s a f e t y / r i s k standards, 88 Log-log transformation, doseresponse, 50,51f Log-probit p l o t examining l e t h a l i t y of three chemicals, 52,53f M Massachusetts s t a t u t e of 1785, 87 Mathematical models f o r e x t r a p o l a t i o n , various models, 137,138 Methotrexate, 27 N-Methylation of p y r i d i n e , species v a r i a t i o n s , 32t Michaelis-Menton equation, 43,44 Mine Enforcement Safety and Health Review Commission, exemption from conducting regulatory impact analyses, 169 Modeling and uncertainty, 100 Modeling, k i n e t i c , using the physiological-anatomical approach, 33 Morphology, i n t e r s p e c i e s d i f f e r e n c e s , 24-26 Ν Nasopharyngeal, deposition of gases and p a r t i c l e s , 26 Nasopharynx d i v e r s i t y between rodent and man, 26 tumors, exposure t o formaldehyde, 26 National Cancer I n s t i t u t e , screening t e s t s and model choice, 137 National Toxicology Program, 17 No-observed-effect l e v e l s (NOELs), 5 a p p l i c a t i o n of safety f a c t o r s t o , 6 confidence i n t e r v a l , 136 d e f i n i t i o n , 16 "pseudo", d e f i n i t i o n , 16 use i n estimating safe exposure l e v e l s , 16 Normal equivalent d e v i a t i o n (NED), 50 Nuclear Regulatory Commission, exemp t i o n from regulatory impact analyses, 169 0

Occupational r i s k s of death i n U.S. i n d u s t r i e s , 103t Occupational Safety and Health Act landmark 1980 benzene case, 89 of 1970, 163 Occupational Safety and Health A d m i n i s t r a t i o n , generic regulatory p o l i c i e s , 159

Occupational Safety and Health Review Commission, exemption from regulatory impact analyses, 169 O f f i c e of Management and Budget, reviewer of regulatory impact analyses, 168 Oleomargarine Act, 85 Oxidative metabolism of xenobiotic compounds by man, as major deter minant i n t o x i c i t y , carcinogen i c i t y , t e r a t o g e n i c i t y , 33 Ρ PASCAL—See DEMOS PCB p r o v i s i o n s , 92 Permissible exposure l i m i t s (PELs), 6 Pharmokinetic models, c h a r a c t e r i z a t i o n s , 27 P o l i c y a n a l y s i s , o b j e c t i v e , 116 P u b l i c perception, of governmental r e g u l a t i o n s , 164-66 Q Q u a n t i t a t i v e assessment i n r i s k management, 113-29 Quantitative p o l i c y a n a l y s i s , a t t r i b u t e s , 116 Quantitative r i s k assessment dealing with u n c e r t a i n t i e s , 113,116-18 and policy-making process, 115 problems of data e x t r a p o l a t i o n , 98,99f,101-5,110 reasons f o r undertaking, 113-15 sources of uncertainty, 18-19,118-20

R Radiation exposure, models used i n estimating r i s k s from, 106 Reactive intermediates and carcinogens, 30-32 Regulation a p p l i c a t i o n of Regulatory Impact Analysis t o h e a l t h , s a f e t y , and environmental, 168 b e n e f i t vs. problems, p u b l i c perception, I66t consideration of c o s t s , p u b l i c perception, I65t,l66t Regulatory c o n t r o l mechanisms i n f e d e r a l health and safety s t a t u t e s , 86 Regulatory costs and b e n e f i t s , s o c i e t a l background, 164 Regulatory decisions e x t r a p o l a t i o n data from animals, 93


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ASSESSMENT A N D M A N A G E M E N T O F C H E M I C A L RISKS

Regulatory decisions—Continued increased r e l i a n c e on q u a n t i t a t i v e s a f e t y / r i s k estimates, 93 l i m i t s of detection methodology, 93 new products, corporate a n t i c i p a t i o n , 158-59 safety f a c t o r s , 93 and t o x i c i t y data, 93 Regulatory impact analyses Chemical Manufacturers A s s o c i a t i o n , p o s i t i o n , 170 i n d u s t r y perspectives, 161-73 review by O f f i c e o f Management and Budget, 168 review by P r e s i d e n t i a l Task Force on Regulatory R e l i e f , 168 Regulatory Impact Analysis (RIA) a p p l i c a t i o n to h e a l t h , s a f e t y , and environmental r e g u l a t i o n , 168 data r e q u i r e d , 167-68,169 encompassing information f o r c o s t - b e n e f i t a n a l y s i s of proposed r u l e and determination of c o s t - e f f e c t i v e ness of r e g u l a t o r y aDDroach. 168

exemption of independent regulatory agencies, 169 Section 3 of 1981 Executive Order, 167 Resource Conservation and Recovery Act of 1976, 163 Risk d i s t i n c t i o n between acceptable and assessment, 152 models f o r the estimation o f , 106 p u b l i c perceptions vs. s t a t i s t i c a l evidence, 152 q u a n t i t a t i v e comparison, 110 Risk assessment and acceptable r i s k , d i s t i n c t i o n , 152 a n t i c i p a t i o n of regulatory d e c i s i o n i n product development, 158-59 assumption r i s k i s dependent on t o t a l cummulative exposure, 75 Chemical Manufacturers A s s o c i a t i o n p o s i t i o n on importance of independent peer review of data, 171 conceptual b a s i s , 3-12 construction of a hazard index, 109,110t definition, 9 on e x i s t i n g chemicals, 155-56 expected value o f i n c l u d i n g uncert a i n t y (EVIU),117 e x t r a p o l a t i o n of dose-response curve to low doses, mathematical models, 137 formalized by corporate actions on a case-by-case b a s i s , 148

Risk assessment—Continued integrated i n t o other aspects of corporation, 157 integrated i n t o research, development, and commercial i z a t i o n c y c l e of a product, 153 i n v o l v i n g p r i v a t e and p u b l i c d e c i s i o n s , 161 lack of a c t u a r i a l data, 3 l e g a l considerations under f e d e r a l regulatory s t a t u t e s , 83-95 major p r i n c i p l e s of process i n the corporation, 149-50 modelling, example, 100-1 new approach to assessing r i s k s , 8 and p o l i c y making process, 115 as p r o b a l i s t i c a n a l y s i s , 121 quantitative d e a l i n g with u n c e r t a i n t i e s , 113,116-20 problems of data extrapol a t i o n , 98,99f,101-5,110 reasons f o r undertaking, 113-15 as single-value-best-estimate a n a l y s i s , 121 as a staged process i n the corporation, 157t s t a t u t o r y and regulatory h i s t o r y , 83-86 system boundaries, 98-100 t r a d i t i o n a l safety assessment schemes, 5-8 types o f corporate decisions r e l a t ing t o , 150-52 uncertainty a n a l y t i c a l s t r a t e g i e s and t o o l s f o r d e a l i n g with, 120 i n the value of model c o e f f i c i e n t s , 120 use of l i n e a r model, dose and e f f e c t r e l a t i o n s h i p , 108 use of modelling, 100 vs. safety e v a l u a t i o n , 131-145 vs. t r a d i t i o n a l safety assessment, 10 Risk comparisons, 97 Risk concerns, chronology of growth o f , 147-49 Risk determination p u b l i c concerns, 149 corporate p o l i c i e s , 151 Risk management a d v e r s a r i a l r e l a t i o n s h i p o f the i n s t i t u t i o n s involved, 126,128 d e f i n i t i o n , 161 i n d u s t r i a l enterprises and governmental i n t e r v e n t i o n , 161 need f o r consensus-based approaches, 128 q u a n t i t a t i v e assessment i n , 113-29 Risk measurement, system boundaries, 98-100


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INDEX

s Safety assessment schemes acceptable d a i l y Intake (ADI), 6 and carcinogens, 7 determination of safe exposure levels, 5 l i m i t a t i o n s , 6-8 no-observed e f f e c t l e v e l s (NOELs), 5 permissible exposure l i m i t s (PELs), 6 s e l e c t i o n of safety f a c t o r s , 7 threshold dose, 6 t r a d i t i o n a l , 5-8 Safety evaluation v s . r i s k assessment, 131-145 Safety f a c t o r s a p p l i c a t i o n t o determine l e v e l of exposure, 5 problems with use, 135 r o l e i n determining r i s k , 132,134-35 s e l e c t i o n as a matter of p o l i c y not science, 7 t o x i c i t y assessment, 134 t r a d i t i o n a l methods o f r i s k assessment, 132 t r a d i t i o n a l use of "expert judgement", 134 t r a d i t i o n a l l y set a t 100, 134 S a f e t y - r i s k standards, classes adopted i n f e d e r a l s t a t u t e s , 86-91 Schreider and Raabe, nasopharynx s t u d i e s , 26 Semilog-dose-response curve, 47,48f Shattuck r e p o r t , 1850, Importance of s a n i t a t i o n of p u b l i c h e a l t h , 85 S t a f f o r d , Senator Robert T., opposi t i o n t o use of cost b e n e f i t a n a l y s i s i n environmental i s s u e s , 169 Supreme Court Cotton Dust d e c i s i o n i n 1981, 169 d e c i s i o n on Occupational Safety and Health Administration's s t a n dard f o r benzene, 149,159

Τ Task Force on Regulatory R e l i e f , 167,168 T e r a t o g e n i c i t y , o x i d a t i v e metabolism of xenobiotic compounds by man, as major determinant, 33 Threshold d e f i n i t i o n , 68 dose-response, d e f i n i t i o n , 38 Threshold dose, safety assessment schemes, 6 Toxic agents assumption that r i s k i s dependent on t o t a l cummulative exposure, 75 thresholds, c o n t r o v e r s i a l i s s u e , 69

Toxic chemicals end e f f e c t on mammalian organism, 17,l8f entry i n t o human body, 17 procedure t o determine e f f e c t of exposure, 19 Toxic Substances Control Act, 89,91,92,155,163 Toxicity chemicals, determined l a r g e l y by animal experimentation, 23 chemicals, i n t e r s p e c i e s e x t r a p o l a t i o n , 23-35 o x i d a t i v e metabolism of xenobiotic compounds as major determinant o f , 33 T o x i c i t y assessment, use of s a f e t y f a c t o r s , 134 T o x i c i t y data, and regulatory d e c i s i o n making, 93 Toxicity tests b a c t e r i a l revertant t e s t s , 17 d i f f i c u l t y of measurement o f inhaled t o x i c a n t , 27 extensive and poor metabolizers, 30-32 e x t r a p o l a t i o n of data from t e s t species t o humans, 15 group s i z e , 15 performed simultaneously w i t h new product development, 153 problems i n chronic, 144 short term t e s t i n g using i s o l a t e d c e l l or enzyme systems, 17 s t a n d a r d i z a t i o n and r e s u l t a n t shortcomings, 15 use i n estimating r i s k s t o human h e a l t h , 13-22 use of h i g h l y inbred s t r a i n s , 15 use o f human subjects, 16 use of organ f u n c t i o n t e s t s , 17 use o f smaller v s . l a r g e r species, 15 Toxicologist r o l e i n d e f i n i n g shape o f doseresponse curves based on theo r e t i c a l and e m p i r i c a l s t u d i e s , 54 r o l e i n r i s k assessment, 131-32 Toxicology acceptable d a i l y intake (ADI), 6 carcinogens, concept of r e a c t i v e intermediates, 30-32 e v o l u t i o n , 14-15 i n h a l a t i o n , a p p l i c a t i o n o f mathe m a t i c a l models, 27-30 mathematical models, 27 new r o l e , 8 no-observed e f f e c t l e v e l s (NOELs), 6 permissible exposure l i m i t s (PELs), 6


184

ASSESSMENT A N D M A N A G E M E N T O F C H E M I C A L RISKS

Tox i c o l o g y — C o n t i n u e d and r i s k assessment, 132 s h i f t i n emphasis from acute poisoning t o l i f e t i m e exposure t o low l e v e l s , 132 threshold dose, 6 t r a d i t i o n a l role of toxicologists i n determining safe exposure levels, 5 Transportation of Explosives Act of 1909, 86,87

Tumors, n a s a l , formaldehyde exposure, 26

V i r t u a l l y safe dose (VSD) d e f i n i t i o n , 58 v a r i a t i o n because of l i m i t e d number of animals a t each dose l e v e l , 72, 74

Production and indexing by Anne Riesberg Jacket design by Anne G. Bigler Elements typeset by Hot Type Ltd., Washington, DC Printed and bound by Maple Press Co., York, PA


Assessment and Management of Chemical Risks - ACS Publications

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