Drinking Water and Health -- Copyright -- List of Participants -- Preface -- Contents -- 1 Executive Summary -- DEVELOPMENTAL TOXICITY -- REPRODUCTIVE TOXICITY -- NEUROTOXICITY -- CARCINOGENESIS -- DOSE-ROUTE EXTRAPOLATION -- THE USE OF EPIDEMIOLOGICAL STUDIES IN RISK ASSESSMENTS -- A FRAMEWORK FOR RISK ASSESSMENT -- TOXICOLOGICAL ASSESSMENT OF 14 COMPOUNDS -- 2 Developmental Effects of Chemical Contaminants -- INFLUENCE OF TIME OF EXPOSURE -- PATTERNS OF DOSE RESPONSE IN LABORATORY ANIMAL STUDIES -- EXTRAPOLATION OF ANIMAL DATA TO HUMANS -- Spectrum of End Points -- Concordance of Results from Animal and Human Studies -- INTERPRETATION OF ANIMAL DATA -- Quality and Quantity of Data -- Relationship between Maternal and Developmental Toxicity -- Selection of the NOEL/LOEL -- RISK ASSESSMENT -- Quantitative Assessment of Developmental Toxicity -- Selection of the Safety Factor -- REFERENCES -- 3 Reproductive Toxicology -- SUSCEPTIBILITY OF THE NONPREGNANT FEMALE TO REPRODUCTIVE IMPAIRMENT -- Maturation of the Female Reproductive System -- Oocyte Toxicity -- Effects of Radiation on Oogenesis -- Effects of Xenobiotic Compounds on Oogenesis -- Polycyclic Aromatic Hydrocarbons (PAHs) -- Antineoplastic Agents -- Alterations in Reproductive Endocrinology -- Endocrine Alterations in the Perinatal Period -- Cns-Mediated Endocrine Alterations in the Adult -- Test Systems for Detecting Female Infertility -- SUSCEPTIBILITY OF THE MALE TO REPRODUCTIVE IMPAIRMENT -- Maturation of the Male Reproductive System -- Sperm Toxicity -- Effects of Radiation on Spermatogenesis -- Test Systems for Evaluating Male Reproductive Toxicity in Laboratory Animals -- Entry-Level Testing -- Human Test Systems -- Sperm Morphology -- Sperm Motility -- Semen Analysis -- Sperm Concentration -- Sperm Chromosome Complement -- Sperm-Cervical Mucus Interaction -- Sperm-Oocyte Interaction.

Examination of Seminal Fluid -- GERM CELL MUTAGENESIS IN MALES AND FEMALES -- Test Systems for Germ Cell Mutations -- Dominant Lethal Test -- Heritable Translocation Test -- Specific Locus Test -- RISK ASSESSMENT IN REPRODUCTIVE TOXICOLOGY -- APPENDIX: DETAILS OF TEST PROTOCOLS FOR REPRODUCTIVE TOXICOLOGY TESTING -- MULTIGENERATION TEST -- FERTILITY ASSESSMENT BY CONTINUOUS BREEDING -- SEGMENT I STUDIES: GENERAL FERTILITY AND REPRODUCTIVE PERFORMANCE -- TIME OF VAGINAL OPENING IN THE RAT PUP -- UTERINE EPITHELIAL HYPERTROPHY -- PRIMORDIAL OOCYTE DESTRUCTION IN JUVENILE MICE -- SPERM PRODUCTION RATES IN RATS -- ASSESSMENT OF EPIDIDYMAL SPERM NUMBERS AND TRANSIT TIMES -- ASSESSMENT OF SPERM MOTILITY -- HISTOLOGICAL EVALUATION OF THE TESTIS -- REFERENCES -- 4 Neurotoxic Effects -- THE HUMAN NERVOUS SYSTEM IN HEALTH AND DISEASE -- Gross Structure and Function -- Cellular Structure and Function -- Normal Developmental Structure and Function -- Neuroteratology and Psychoteratology -- Neurotoxic Responses after Birth and at Maturity -- Susceptibilities of Special Populations -- The Aged -- The Diseased -- STUDIES IN HUMANS -- Occurrence of Neurological Disease -- Epidemiological Studies -- Controlled and Other Studies -- STUDIES IN ANIMALS -- INTERSPECIES EXTRAPOLATION -- RISK ASSESSMENT -- REFERENCES -- 5 Mechanisms of Carcinogenesis -- THE MULTISTAGE THEORY OF CARCINOGENESIS -- Initiation -- Promotion -- Progression -- Cocarcinogenesis -- ONCOGENE ACTIVITY -- MODEL SYSTEMS -- Mouse Skin -- Rat and Mouse Liver -- Other Animal Systems -- Studies in Humans -- GENETIC TOXICITY -- THE ROLE OF THE IMMUNE SYSTEM IN CARCINOGENESIS -- CARCINOGEN EVALUATION -- Animal Bioassays -- Short-Term Tests -- Germ Cell Mutagenesis -- STRUCTURE-ACTIVITY RELATIONSHIPS -- RISK ASSESSMENT -- REFERENCES.

6 Dose-Route Extrapolations: Using Inhalation Toxicity Data to Set Drinking Water Limits -- BACKGROUND -- Routes of Exposure -- Dose-Response Curves -- Measurement of Tissue Dose -- PHARMACOKINETIC MODELS -- Data-Based Inhalation Models -- Physiologically Based Models -- An Inhalation Model -- An Oral Model -- TWO EXAMPLES OF DOSE-ROUTE EXTRAPOLATIONS -- Trichloroethylene -- Benzene -- INTERSPECIES EXTRAPOLATION -- Allometric Relationships -- Tissue Dose Scale-Up -- Short-Lived Reactive Metabolites -- Interspecies PB-PK Model Simulations -- Incorporating Time-Dependent Physiological and Metabolic Changes -- PB-PK MODELS IN RISK ASSESSMENT -- Extending Basic Models to Accommodate Reality -- Appendix A: Metabolic Processes in the Respiratory Tract, the Gastrointestinal Tract, and the Liver -- THE RESPIRATORY TRACT: ABSORPTION, METABOLISM, AND PRESYSTEMIC ELIMINATION -- Pulmonary Structure and Cell Types -- Metabolic Properties of Lung Cells -- Clara Cells -- Alveolar Type II Cells -- Other Pulmonary Cells -- Elimination of Compounds by the Lung -- THE GASTROINTESTINAL TRACT: ABSORPTION, METABOLISM, AND PRESYSTEMIC ELIMINATION -- The Absorption Process -- Anatomical Regions of the Gastrointestinal Tract -- Buccal Cavity and Esophagus -- Stomach -- Small Intestine -- Colon and Rectum -- Presystemic Elimination -- Metabolism Within the Intestinal Lumen -- Metabolism by Gastrointestinal Mucosa -- METABOLISM IN THE LIVER -- Appendix B: Definitions of Symbols and Abbreviations -- REFERENCES -- 7 Data on Humans: Clinical and Epidemiological Studies -- CLINICAL OBSERVATIONS: CASE REPORTS -- EPIDEMIOLOGICAL OBSERVATIONS -- Early Studies -- Descriptive Epidemiology -- Analytical Epidemiology -- Case-Comparison and Cohort Studies -- Experimental or Intervention Studies -- PRINCIPLES, PROBLEMS, AND LIMITATIONS OF EPIDEMIOLOGY -- Statistical Significance and Power.

Study-Related Limitations -- Inference and Quantification -- Nature of Populations Studied -- Mechanisms of Biological Action -- RISK ASSESSMENT -- Relative Risk -- Attributable Risk -- Additivity -- Application to Drinking Water Studies -- REFERENCES -- 8 Risk Assessment -- PREVIOUS SAFE DRINKING WATER COMMITTEES' VIEWS ON RISK ASSESSMENT -- Issues Concerning Threshold -- Carcinogenic and Mutagenic Effects -- Noncarcinogenic Effects -- Safety, or Uncertainty, Factors -- The Use of Animal Data to Predict Human Risk -- Combined Exposures -- Reliability of Risk Estimation -- Noncarcinogens -- Estimates of Exposure from Different Sources and Various Routes -- Water -- Food -- Air -- Workplace -- Household -- PHARMACOKINETICS -- INTER-AND INTRASPECIES EXTRAPOLATION -- CARCINOGENESIS -- The NOEL -- Quantitative Assessment -- The Multistage Dose-Response Model -- Threshold Models -- DEVELOPMENTAL AND REPRODUCTIVE EFFECTS -- The NOEL -- Quantitative Assessment -- NEUROTOXICITY -- The NOEL and LOEL -- Quantitative Assessment -- CONCLUSIONS AND RECOMMENDATIONS -- Carcinogenicity -- Developmental and Reproductive Toxicity -- Neurotoxicity -- REFERENCES -- 9 Toxicity of Selected Contaminants -- ACRYLAMIDE -- Metabolism -- Health Aspects -- Conclusions And Recommendations -- CARBAMATE PESTICIDES (ALDICARB, DIALLATE, AND SULFALLATE) -- ALDICARB -- Health Aspects -- Conclusions and Recommendations -- DIALLATE -- Metabolism -- Health Aspects -- Conclusions and Recommendations -- SULFALLATE -- Metabolism -- Health Aspects -- Conclusions -- DIBROMOCHLOROPROPANE -- Health Aspects -- Conclusions and Recommendations -- CHLOROPROPANES AND CHLOROPROPENES -- Metabolism -- Health Aspects -- Conclusions and Recommendations -- DI(2-ETHYLHEXYL) PHTHALATE (DEHP) -- MONO(2-ETHYLHEXYL) PHTHALATE (MEHP) -- Metabolism -- Health Aspects -- Conclusions and Recommendations.

ETHYLENE DIBROMIDE -- Health Aspects -- Conclusions and Recommendations -- NITROFEN -- Metabolism -- Health Aspects -- Conclusions and Recommendations -- PENTACHLOROPHENOL -- Metabolism -- Health Aspects -- Conclusions and Recommendations -- TRICHLORFON -- Metabolism -- Health Aspects -- Conclusions And Recommendations -- CONCLUSIONS AND RECOMMENDATIONS -- REFERENCES -- Committee Biographies -- Index.