The most recent volume in the Drinking Water and Health series contains the results of a two-part study on the toxicity of drinking water contaminants. The first part examines current practices in risk assessment, identifies new noncancerous toxic responses to chemicals found in drinking water, and discusses the use of pharmacokinetic data to estimate the delivered dose and response. The second part of the book provides risk assessments for 14 specific compounds, 9 presented here for the first time.
- 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
- 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
- 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
- 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
- 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
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