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Index acceptable daily intake, 2, 25 carcinogens, considerations of, 3~37 chronic exposure, 2~37 dose-response methodology, 31-37 no-adverse-effect level, 31 uncertainty factors, 36 ACGIH (see American Conference of Governmental Industrial Hygienists) acneiform skin eruptions, iodine effects, 306 acrylonitnle toxicity, 71-76 acute exposure, risk estimation, 2~28 additive effects in drinking water, 27 adequate and safe intake, 372 chromium, 366, 372 copper, 313, 372 fluoride, 280, 372 manganese, 334, 372 molybdenum, 361, 372 potassium, 294, 372 selenium, 325, 372 sodium, 287, 372 ADI (see acceptable daily intake) alcohol, magnesium depletion effects, 274 aldosteronism, magnesium malabsorp- tion, 273 alkalosis, potassium deficiency, 295 aluminum fluoride interaction, 282 407 phosphorus interaction, 278 American Conference of Governmental Industrial Hygienists, 101 anemia iron deficiency, 309 manganese interaction, 336 animal tests acrylonitrile, 73-76 antimony, 78 80 benzene, 83 84 benzene hexachlonde, 87~8 bromodichloromethane, 189 bromoform, 189 cadmium, 9~95 carbon tetrachloride, 96 97 catechol, 191-192 chlorite, 197 bis(2-chloroethyl)ether, 89 bis(2-chloropropyl)ether, 90 chloroform, 203-204 dibromochloromethane, 205 dichlorodifluoromethane, 102-103 1,2-dichloroethane, 10~110 epichlorohydrin, 11~122 ethylene dibromide, 99 100 glyoxylic acid, 209 210 hexachlorobenzene, 21 1-214 iodine, 221-224 lindane, 87~8 nonanal, 226

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408 Index PCB, 131-133 resorcinol, 22~230 1,1,1-trichloroethane, 14~152 trichloroethylene, 15~164 trichlorofluoromethane, 167 uranium, 17~177 antagonistic effects in drinking water, 27 anticonvulsants, magnesium use, 274 antimony toxicity, 77~0 Antofagasta, Chile, arsenic in drinking water, 338 Aroclor, 13 1-133 arsenic nutrition, 337-345, 37~375 cadmium interaction, 344 arsenic trioxide toxicity, 342 arteriosclerotic stroke, risk estimate studies, 22 (see also cardiovascular disease) asbestos, lung problems, 356 Australia, hypertension- salt intake ef- fects, 290 Bacillus subtilis, 120 background response (see risk estimation) bakery goods, potassium additives, 293-294 barbiturates, diuretic effects, 290 BDPF (see bile duct-pancreatic fluid Row) beer, diet sodium effects, 291 benzene toxicity, 8~86 benzene hexachlonde toxicity, 86 88 BHC (see benzene hexachloride) bile duct-pancreatic fluid flow, 97 biochemical interactions, toxicity from chemicals, 45~6 blood pressure, sodium effects (see also cardiovascular disease), 28~289 borne cancer (see cancer) bromate toxicity, 181-187 bromide toxicity, 181-187 bromine toxicity, 181-187 bromism, chloride interaction, 301 bromodichloromethane toxicity, 887~88 bromoform toxicity, 189 bronchial diseases (see respiratory diseases) cadmium absorption, calcium effects on, 271 arsenic interaction, 344 toxicity, 91-96 1,25-dihydroxycholecalciferol, synthe sis inhibition, 271 selenium interaction, 32~329 zinc interaction, 317 calcitonin, magnesium interaction, 27~275 calcium nutrition, 26~271, 37~375 fluoride interaction, 282 lead poisoning susceptibility, 270 water hardness relationship, 272 zinc interaction, 317 calcium carbonate, water hardness mea sure, 21 calcium phosphate, manganese interac tion, 336 Canada magnesium in water, 272 myocardial infarction accidental death comparisons, 22 cancer arsenic effects, 343 bladder-chloroform risks, studies, ~7 bone, magnesium malabsorption, 273 chemotherapy, 29 chloroform relationship, 5, 7 frequency, 5-21 liver and kidney studies, 10 mortality rates-THM relationship, 13-18 Ohio River Valley Basin water quality studies, 1 1 'safety factor" approach, 3~39 (see also carcinogens) cancer in humans epidemiological studies, 1-2, 5-21 skin, Taiwan, arsenic in well water, 343-344 THM bladder relationship, 1, ~9 carbon tetrachloride toxicity, 9~98 carcinogenesis arsenic, 344 dose-response models, 58~0 multistage model, 53, 59 carcinogens ADI theoretical data, 3~37 dietary components, 52 ethylenedibromide risk estimation, 100 groundwater and surface water con- tamination studies, ~7 (see also cancer)

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Index 409 carcinoma (see cancer; carcinogens) cardiac glycosides, potassium depletion effects, 296 cardiovascular disease arsenic relationship, 343 drinking water hardness relationship, 1 - 2 risk estimation studies, 22 water hardness relationship, 22 catechol toxicity, 19~192 cathartics, magnesium use, 274 cattle, iodine intake, 222 central nervous system tetrachloroethylene effects, 136 1, 1,1-trichloroethane ejects, 146 149 CHE (see cholinesterase) chemicals, evaluation of toxicity, 67-70 chemicals toxicity, biochemical interac- tions, 45~6 chlorate, 198 200 chloride nutrition, 298-302, 37~375 bromide interaction, 301 chlorine dioxide toxicity, 193-196 chlorine oxides, uses, 193 chlorite, 197 chloroamines toxicity, 20~203 chloroamino acids toxicity, 202-203 bis(2-chloroethyl)ether, in animals, 89 chloroform epidemiological studies ~7 toxicity, 203-204 bis(2-chloropropyl)ether toxicity, 9~91 cholinesterase, 3 1 chromium nutrition, 266, 364 368, 37~37S vanadium interaction, 368 chronic exposure ADI, 2~37 dose-response methodology, 3 1-37 ' safety factor'' approach, 30 cobalt, nutritional value, 266 cocarcinogenesis, 51, 53 . . . . . . . compounds, combinations, Joint action, 27 condiments sodium, dietary source, 284 copper nutrition, 3 12-3 15, 3 1~3 19, 37~375 iron interaction, 311 molybdenum interaction, 314 sulfur interaction, 314 zinc interaction, 314 copper pipes, soft water reactions, 312 Council of Europe, octanal review, 227 CVD (see cardiovascular disease) cyanoethylene (see acrylonitrile) cytochrome P-450, interspecies micro- somes content, 50 DCE (see 1,2-dichloroethane) dental caries, fluoride requirements, 280 dental health, 28~281 dermatitis nickel toxicity, 34~349 selenium relationship, 327 diabetes mellitus, magnesium malabso~p- tion, 273 Diazinon, 3 1 dibromochloromethane toxicity, 20~206 1,2-dibromoethane (see ethylene dibromide) dichlorodifluoromethane toxicity, 101-104 1,2-dichloroethane toxicity, 1(0111 2,4-dichlorophenol toxicity, 206 207 dichotomous response models low-dose carcinogenic risk estimation, 37 risk estimation, 2 dietary intake, human, 37~375 arsenic, 337-341 calcium, 268, 269 chloride, 298 299 chromium, 364 366 copper, 312-313, 31~319 fluoride, 279 280 iodine, 302-304 iron, 309 310, 31~3]9 magnesium, 272 manganese, 331-334 molybdenum, 357-359 nickel, 34~347 potassium, 293-294 phosphorus, 27~277 selenium, 321-323 silicon, 355 sodium, 28~287 vanadium, 35~351 zinc'316, 318-319 digitalis, potassium depletion effects. 296 1 25-dihydroxycholecalciferol, 271, 27~275 diuretics, 290, 296

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410 Index dose-response models, 31-37, 58-60 drinking water contribution to mineral nutrition, 369, 374-375 arsenic, 345 calcium, 271 chloride, 301-302 chromium, 369 copper, 31~315 fluoride, 282 iodine, 307 iron, 311 magnesium, 275 manganese, 337 molybdenum, 364 nickel, 349 potassium, 297 phosphorus, 278 selenium, 330 silicon, 357 sodium, 292 vanadium, 354 zinc, 317 drugs, iodine content, 305 ECH (see epichlorohydrin) EDTA (see ethylenediaminetetraacetic acid) elemental arsenic, toxicity, 342 elements in drinking water, 373-375 environmental contaminants, 27 Environmental Protection Agency chemicals in water supplies. 5 THM concentrations survey 13- 18 THM studies. 5 6 enzymes molybdenum content, 361 EPA (see Environmental Protection Agency ) National Statistical Assessment of Rural Water Conditions. 373 NOMS. 81 NORS. 13. 17 epichlorohydrin tox icily 111- 124 epidemiological studies. 1-2 cancer~rinking water relationship, ~21 case-control studies, 17- 19 cohort studies. 19 drinking water contaminants-cancer incidence relationship, 5~56 epidemiology, risk assessment, 5~56 Erie County, N.Y., cancer chlorinated water studies, 10 erythrosine, iodine dietary content, 303 Escherichia coli, 161 ethylenediaminetetraacetic acid, 353 ethylene dibromide, 98 100 FDA (see Food and Drug Administration) fiber (dietary), zinc interaction, 317 fish products, fluoride content, 279 fluondation, public water supplies, 279 fluoride, 27~283, 363 aluminum interaction, 282 calcium interaction, 282 magnesium interaction, 282 molybdenum interaction, 363 food additives, chronic exposure, 3~31 Food and Drug Administration, 331 arsenic in food, 337-338 food coloring agent (see erythrosine) food preservatives, 284 Fowler's solution, 343 gastrointestinal disease, magnesium malabsorption, 273 generally recognized as safe, octanal re- view, 226 glucose tolerance factor, 365, 368 glyoxylic acid, 207-210 goiter 30~306 (see (l Is`' thyroid) goitrogens, 305 gout, molybdenum exposure, 361 GRAS (see generally recognized as safe) Graves' disease (see thyrotoxicosis) Great Britain, antimony effects in factory workers, 79 groundwater, ~7 GTF (see glucose tolerance factor) Hagerstown, Md., water quality-cancer effects, 10 halogens, germicidal action, acute ef- fects, 185 HCB (see hexachlorobenzene) HCP (see hexachlorophene) hemoglobin, repletion, 336 hepatolenticular degeneration, 314

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Index 411 hexachlorobenzene toxicity, 21~215 hexachlorophene toxicity, 32 hexavalent chromium, 365, 367-368 hitness'' models (see target theory) hydrocarbons, vanadium content, 3S1 hydroch~onc acid, chloride anion, 298 3-nitro-4-hydroxyphenylarsonic acid, toxicity, 342 hyperkeratosis, 343 hyperparathyroidism, magnesium malab- sorption, 273 hypertension Australian studies, 290 risk estimation studies, 22 salt-diet relationship, 290 sodium effects, 28~289 hypocalcemia, 270 hypocalcemic tetany, phosphorus allow- ance in infants, 277 hypochloremic alkalosis, chloride tox- icity, 300 hypoglycemic drugs, sodium deficiency effects, 290 hypokalemia, 29~296 hyponatremia, 290 291 hypothyroidism, 305 India, molybdenum exposure. 362 initiation-promotion. regulatory implica- tions, 53 inorganic arsenicals, toxicity, 339, 342 International Agency for Research on Cancer, ECH tests, 122 interspecies toxicology, 2~29 iodate toxicity (see iodine toxicity) iodide toxicity (see iodine) . . 10( Ine lead interactions 30~307 nutrition 302-309. 374-375 toxicity 2 1 5-225 iodism, 21~220 iron nutrition, 30~312, 31~319. 37~375 absorption impaired by nickel defi- ciency, 349 lead interaction, 311 manganese interaction, 31 1, 336 molybdenum interaction 363 nickel interaction. 349 zinc interaction. 311 itai itai disease. calcium deficiency ef- fects. 271 Japan iodide intake effects, 220 itai itai~alcium deficiency relation- sh~p, 271 manganese toxicity, 336 lakes, phosphorus content, 276 Lane County, Oreg., arsenic in drinking water, 338 lead iodine interaction, 306 307 iron interaction, 311 poisoning, calcium intake effects, 27~27 1 leukemia, benzene relationship, 82 lindane (see also benzene hexachloride), 87~8 linear, no-threshold model, 37, 40 linear risk estimation model, 2 lithium, sodium interaction, 292 logistic models low-dose carcinogenic risk estimation, 4 1~2 risk estimation, 2 Los Angeles County. Califwater qual ity study, 1 1 Louisiana cancer rates~rinking water relation ship, 5 water quality studies 8 lungs silica and asbestos problems. 356 magnesium nutrition 272-276. 37~37- calcium interaction 274 fluoride interaction, 282 phosphorus interaction. 274 potassium interaction 274 manganese nutrition. 331-337 37~375 calcium phosphate interaction. 336 iron interaction 3 1 1 . 3 36 mathematical models. risk assessment. 54 maximum permissible concentration uranium tests 177 maximum tolerated dose. 10() interspecies toxicology' 29 mercury, selenium interaction 328-3~9 methylene chloride toxicity. 124 128 MFO (set mixed function vxidase)

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412 Index mineral intake. 267 mineral nutrition. 265, 267 (so als`' drinking water contribution to mineral nutrition) Mississippi River drinking water~ancer relationship, 5 water quality studies. 8 mixed function oxidase. trichloroethylene effects. 162 models dose-response, 5~60 hitness'' (. target theory) mathematical, risk assessment, 54 multistage. carcinogenesis. 54. 58 risk estimation, 2-3 single-hit multistage relationship, 59 theoretical risk estimation, 52-54 molybdenosis, 361 molybdenum nutrition, 357-364. 37~375 copper interaction, 314, 362-363 fluoride interaction, 363 iron interaction, 363 sulfides interaction, 363 mortality rates-halomethane levels, 1~15 MPC (salt maximum permissible concentrations) MID (scar maximum tolerated dose) mucopolysaccharide, 355-356 multistage models, carcinogenesis, 54, 58 municipal wat.er supply (~ public water supplies) myxedema. iodine-goiter relationship. 305-306 National Air Sampling Network. 365 National Cancer Institute chloroform studies. 5, 7 DCE tests. 109 tetrachloroethylene studies. 139 National Cancer Institute Bioassay Pro- gram. 151 National Organic Monitoring Survey. 81 National Organics Reconnaissance Sur- vey, 13, 17 National Statistical Assessment of Rural Water Conditions, 373 NCI (see National Cancer Institute) NCTHM (see nonchloroform trihalomethane ) New Jersey . water quality study, 12 New York, upstate, water quality. 9-10 New Zealand. selenium intake low, 321 nickel nutrition, 345-350 iron interaction, 349 NOMS (sale National Organic Monitoring Survey) nonchloroform trihalomethane. 13. 17 nonanal toxicity, 225-226 NORS (scat National Organics Recon- naissance Survey) no-threshold risk estimation model, 2 oceans. iodine consent q 303 octanal~ 22~227 Ohio River. water quality studies. 8, Ohio River Valley Basin, water quality~ancer studies, I I Olmstead County. Minn., thyroiditis prevalence, 306 organic arsenicals, toxicity 342 osteoporosis calcium loss, 270 fluoride requirements, 280 vitamin D deficiency, 270 osteosclerosis. fluoride intake effects, 281 parathyroid, magnesium interaction' 27~275 PCB (set polychlorinated biphenyl) pentavalent arsenic toxicity, 339 pharmacokinetic considerations dose effects, 46Jr8 species testing, 4~51 phorbol myristate acetate, 122 phosphate (se`, phosphorus nutrition) phosphorus nutrition, 27~279, 37~375 cations interaction, 278 phytate, zinc relationship, 317 Pittsburgh, Pa., water quality study, 12 plumbing systems, copper use, 312 PMA (see phorbol myristate acetate) polychlorinated biphenyl, 128-133 polyvalent cations, water hardness mea- sure, 21 potassium nutrition, 293-298, 308, 37~375 sodium interaction, 292 potassium iodide, to treat thyrotoxicosis, 305

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Index 413 2-propenenitrile (see acrylonitrile) protein, selenium interaction, 329 public water supplies fluoridation, 279 nickel content, 345-347 phosphorus content, 276 sodium content. 28~285 vanadium content, 351 water-softening procedures, 23 pulmonary diseases (~e respiratory diseases) RDA (see recommended dietary allowance) recommended dietary allowance, 4, 267, 369-37 1 calcium, 269, 370. 371 chloride, 300, 370, 37] iodine, 304, 370, 371 iron, 310, 370, 371 magnesium, 272, 370. 371 phosphorus. 277, 370, 371 zinc, 316, 370, 371 requirements arsenic, 341 nickel, 348 silicon, 356 vanadium, 352-353 (as ~ `'I.s`' adequate and safe intake `;ncf recommended dietary allowance) respiratory diseases, arsenic relationship, 343 repletion, hemoglobin, 338 research priorities, future, 23-24 resorcinol, 227-230 rickets, calcium-def~cient diets, 270 risk assessment (see also risk calcula- tions; risk estimation) 5~56 risk calculations 59 risk estimation acrylonitnle~ancer relationship. 76 acute exposure to chemicals in drink- ing water. 2~28 ADI approach, 25 background response, 51, 57-58 benzene, 8~85 cardiovascular disease, 22 cocarcinogenesis, 5 1 DCE, 109, 110 defined, 25 dose-response models. 56 60 drinking water toxic chemicals ef- fects, 2-3 ethylene dibromide-carcinogen rela- tionship, 100 HCB carcinogenicity, 213-214 hypertensive disease, 22 interaction, 51 60 joint toxic action models, 53-54 low-dose carcinogen models, 37~5 models, 2-3 quantitative reliability, 56~0 safety factors, 25-28 statistical data studies, 59 60 tetrachloroethylene carcinogenicity, 139 theoretical models, 52-54 water hardness relationship, 22 (see also risk assessment; risk calculations) rivers, phosphorus content, 276 Safe Drinking Water Acts 1974 (PL93-523), 405 Safe Drinking Water Act, 1977 Amend- ments, 405 Safe Dnnking Water Committee, NAS-NRC, 22 Salmonella typhimurium, 114, 120. 161, 163 salt (see sodium chloride) SDWC (see Safe Drinking Water Com- rruttee, NA~NRC) seafood, iodine content, 303 selenium nutrition, 321-331, 37~375 arsenic interaction, 329, 344 cadmium interaction, 32~329 mercury interaction, 32~329 protein interaction. 329 sulfate interaction, 329 thallium interaction, 32~239 vitamin E interaction. 329 selenosis, 326 serum glutamic-oxaloacetic transaminase 2,4-dichlorophenol tests, 206 toluene effects, 170 trichloroethylene toxicity, 15~159 selenium effects, 328 serum glutamic-pyruvic transaminase, 87. 97 2,4-dichlorophenol tests, 206 toluene effects. 170

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414 Index SCOT (see serum glutamic-oxaloacetic transaminase) SORT (see serum glutamic-pyruvic transaminase) silica, lung problems, 356 silicon nutrition, 35~357 molybdenum interaction, 357 SNARL (see suggested no-adverse response level) sodium nutrition, 283-293, 308, 37~375 lithium interaction, 292 potassium interaction, 292, 297 sodium bromide, 185 sodium chloride, 283-287, 303 soft drinks phosphate consumption, 275-277 sodium content, 287 soft water (see also water hardness), 21, 312 soil molybdenum content, 358 selenium content, 321-322 South Dakota, selenium intake high, 321 species testing, 4~51 spontaneous response (see background response) sulfides, molybdenum interaction, 363 suggested no-adverse-response level, 3-4 70 acute exposure. 68 69 antimony, 80 Aroclor 133- 134 assumptions 69 benzene. 70. 85~6 BHC (lindane), 70, 88 bromide 70. 18~ 187 hromodichloromethane 188 t?romoform ~ 89 cadmium. 70. 9~96 carUc)n tetrachloride. 70. 97~98 catechol 7(), 192 his(2-chlorethyl)ether. 89 bis(2-chloropropylyether, 91 chlorine dioxide. 70. 196 chlorite. 70 197- 198 chloramines, 202 chloroamino acids. 202 chloroform, 70, 204 chronic exposure, 6~70 DCE, 11(~111 dibromochloromethane, 70, 205-206 dichlorodifluoromethane, 70, 103-104 2,4-dichlorophenol, 70, 207 ECH, 70, 123- 124 ethylene dibromide, 10~101 glyoxal, 210 glyoxylic acid, 210 HCB, 70, 21~215 iodate, 224 iodide, 70, 22~225 iodine, 224 methylene chloride, 70, 127-128 methyl glyoxal, 210 PCB's, 70, 133-134 resorcinol, 70, 23~231 safety, uncertainty factors used, 69 tetrachloroethylene, 70, 14~142 toluene, 70, 172-173 1,1,1-trichloroethane, 70, 152-155 trichloroethylene, 70, 164 166 trichlorofluoromethane, 70, 167-168 uranium, 70, 177-178 xylenes, 70, 181 sulfate, dietary, 329 sulfur, copper interaction, 314 surface water, ~7 sweat, sodium loss, 291 swine, iodine intake, 222-223 synergistic effects in drinking water, 27 table salt (see sodium chloride) Taiwan, 343, 338 target theory, 2, 42-43 TCDD (see 2,3,7,8-tetrachlorodibenzo p-dioxin) TO E (A ~ tetrachloroethylene; trichloro ethane; trichloroethylene) 2.3,7 8-tetrachlorodibenzo-p-dioxin, 33-35 tetrachloroethy lene, 1 3= 1 39 theoretical models 52-54 THM (see trihalomethane) thallium selenium interactions 32~329 thorium, 142-144 threshold limit value 101 thyroid 304 thyroid hormones 302 thyroiditis prevalence in Minnesota. 306 thyrotoxicosis 274 305-306 thyroxine, iodine content, 302 time-to-tumor-occurrence models, 2 43-45

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Index 415 tissues arsenic distribution, 339 chromium distribution, 366 manganese distribution, 333, 335 molybdenum distribution, 359-360 nickel distribution, 347 silicon distribution, 355-356 vanadium distribution. 352 TLV (.s`e threshold limit value) tolerance distribution models 2, 4~1 toluene, 16~ 172 Total Diet Study, FDA, 331, 337-338 toxic chemicals, 2-3, 2~29 toxicity biochemical interaction, 45~6 phosphorus deficiency. 278 toxicology, 3~4, 2~29 trace element, iodine . 216 1, I, I-trichloroethane toxicity, 14~155 trichloroethylene toxicity, 155- 166 trichlorofluoromethane toxicity, 16~168 trihalomethane. 1. ~7, 13-18, 19, 55-56 triiodothyronine, 302 trivalent arsenic toxicity, 339 trivalent chromium, 365, 367 United Kingdom, 22 uranium, 173-177 vanadium nutrition, 35~354, 314~375 chromium interaction, 368 vegans, 266 Venezuela, selenium intake, 321 vinyl cyanide (so c acrylonitrile) vitamin D, 270. 277 vitamin E, 325, 329 Washington County, Md., water quality study, 10 water hardness (see als`' soft water), 1-2. 21-22, 267. 271 water intake, 266 water quality future THIN studies, 13, 17 Los Angeles County, Calif., cancer study, 11 . . . . . . . . MISS'SSlppl diver Louisiana cancer studies, 8 NCTHM concentration bladder cancer relationship, 13 New Jersey cancer study, 12 Ohio River cancer studies, 8, 11 Pittsburgh, Pa., cancer studies, 12 THM concentrations-cancer relation- ship, 13-18 upstate New York cancer study, `10 Washington County, Md., cancer study, 10 water-softening (sect als`' soft water; water hardness), 21-23, 285 water supply systems (scar also public water supply), 267 water treatment, 373 WHO (scan World Health Organization) Wilson's disease (scar hepatolenticular degeneration) women, iron requirements, 310 World Health Organization. 30 xylenes toxicity, 17~ 181 zinc nutrition, 315-321, 37~375 copper interaction, 314 iron interaction, 311