Uranium, Plutonium, transplutonic elements. Handbuch der experimentellen Pharmakologie; 36.

More than a year ago the three editors sat down at a table and worked out a set of six chapter headings which they believed might serve, in turn, for each of the three sections of this handbook. (The reader will note a similarity in order of presentation and in emphasis.) However, as our editorial plans progressed it became apparent that for each element and for the element group, there were one or two special topics appropiate for that section alone. Accordingly, in the section on uranium the common pattern holds for Chaps. 1 through 6 which include: an introduction (Chap. 1), a discussion of the physical and chemical properties (Chap. 2), experimental data on animals (Chap. 3), ex­ perimental data on man (Chap. 4), the rationale and development of air con­ centration limits to control industrial worker exposure (Chap. 5), and the prac­ tical problems of applying such limits in the uranium industry (Chap. 6). Chap. 7 entitled "Uranium Mining Hazards" is the subject category which is special for uranium; the chapter brings up to date the account of an important occupational hazard which was first noted by GEORGIUS AGRICOLA (1490-1555).

Uranium.- Preface.- 1 A History of Uranium Poisoning (1824–1942).- I. Early History. Homeopathic Uses.- II. Toxicity of Uranium Compounds.- III. Experimental Nephritis; Kidney.- A. Pathology.- 1. Glomerular Injury vs. Tubular Injury.- 2. Glomerular Lesions.- 3. Tubular Lesions.- 4. Repair of Tubular Injury.- 5. Tolerance.- B. Age.- C. Anuria.- D. Casts.- E. Edema.- F. Diuretics.- G. Kidney Composition.- IV. Experimental Nephritis; Urine.- A. Glycosury and Albuminuria.- B. Urinary Nitrogen.- C. Kidney Function.- D. Urinary Enzymes.- E. Urinary Acetone, Acetoacetic Acid, Phenols, Organic Acids.- F. Urinary Sodium, Chloride, Potassium, Phosphate.- G. Acidosis.- V. Effects of Uranium on the Cardiovascular System.- A. Capillary Permeability.- B. Vessel Tone.- C. Blood Pressure.- D. Cardiac Hypertrophy.- E. Arterial Lesions.- F. Heart Rate.- G. Hemoglobin.- H. Viscosity.- I. Coagulation.- J. Hemolysis.- K. Toxic Serum Factor.- VI. Effects of Uranium on the Blood Chemistry.- A. Nitrogen.- 1. Non-protein Nitrogen.- 2. Rest-N.- 3. Urea-N.- 4. Azotemia.- 5. Uric Acid.- 6. Creatinine.- 7. Ammonia.- 8. Serine.- 9. Xanthoproteic Reaction.- 10. Indican.- 11. Diazo-reacting Substances.- 12. Index of Pathological Change.- B. Acidosis.- C. Other Blood Constituents.- 1. Chloride.- 2. Sodium.- 3. Potassium.- 4. Magnesium.- 5. Calcium.- 6. Sulfate.- 7. Phosphate.- 8. Cholesterol.- 9. Lipids.- 10. Phenols.- 11. Sugar.- 12. Freezing Point.- 13. Refractive Index.- VII. Effects of Uranium on the Liver.- A. Pathology.- B. Biochemistry.- C. Biliary Excretion.- D. Fecal Analysis.- VIII. Effects of Uranium on Muscle.- IX. Effects of Uranium on the Nervous System.- X. Effects of Uranium on Enzymes.- XI. Selected Metabolic Effects of Uranium.- XII. Treatment of Uranium Poisoning.- XIII. Tissue Contents of Uranium in Uranium Poisoning.- References.- 2 Physical and Chemical Properties of Uranium.- I. Physical Properties of Atomic Uranium.- A. Extra-nuclear Properties.- B. Nuclear Properties.- 1. Isotopes.- 2. Nuclear Fission.- a) The Probability of Fission.- b) The Energy Released in Fission.- c) Fission Product Mass Distribution.- d) Charge Distribution.- e) Fission Neutrons.- II. The Chemistry of Uranium.- A. Metallic Uranium.- B. Compounds of Uranium and Non-Metallic Elements.- 1. Uranium Hydride.- 2. Group IIIA — Uranium Borides.- 3. Group IVA — Uranium Carbides and Silicides.- a) Uranium Carbides.- b) Uranium Silicides.- 4. Group VA — Uranium Nitrides, Phosphides, and Arsenides.- a) Uranium Nitrides.- b) Uranium Phosphides.- c) Uranium Arsenides.- 5. Group VIA — Uranium Oxides, Sulfides, Selenides, and Tellurides.- a) Uranium Oxides.- b) Uranium Sulfides.- c) Uranium Selenides.- d) Uranium Tellurides.- 6. Group VIIA — Uranium Fluorides, Chlorides, Bromides, and Iodides.- a) Uranium Fluorides.- b) Uranium Chlorides.- c) Uranium Bromides.- d) Uranium Iodides.- e) Uranium Mixed Halides and Uranium (IV) Borohydride.- f) Uranium Oxyhalides.- g) Uranium Nitrogen Halides.- C. Uranium Salts, Hydrated Oxides, Uranates, and Peruranates.- 1. Uranium (IV) Salts.- a) Carbonates.- b) Sulfates.- c) Oxalates.- 2. Uranium (VI) Salts.- a) Carbonates.- b) Nitrates.- c) Phosphates.- d) Sulfates.- e) Uranyl Halides.- f) Acetates.- g) Oxalates.- 3. Uranium Oxide Hydrates.- 4. Uranates and Peruranates.- D. Uranium in Solution.- 1. Aqueous Solution.- a) Oxidation States.- b) Hydrolysis.- c) Complex Ion Formation.- 2. Physiological Systems.- a) Complexing Agents.- b) Prevention and Therapy of Uranium Poisoning.- E. References to the Analytical Chemistry of Uranium.- References.- 3 Animal Experiments.- I. Introduction.- II. Criteria of Uranium Toxicity in Experimental Animals.- III. Parenteral Administration.- IV. Oral Toxicity of Uranium.- A. Thirty Day Feeding Experiments.- B. One- and Two-year Feeding Experiments.- V. Uranium Compounds Applied to the Skin.- VI. Uranium Compounds Applied to the Eye.- VII. Respiratory Tract Exposure to Uranium Dusts.- A. Studies by Means of Tracheal Insufflation.- B. Toxicity Following Inhalation.- 1. 30-day Studies.- 2. Studies of Toxicity Following Inhalation of Uranium Compounds for One Year.- a) Uranyl Nitrate Hexahydrate.- b) Uranium Hexafluoride.- c) Uranium Tetrachloride.- d) Uranium Dioxide.- e) Uranium Tetrafluoride.- 3. Studies of Toxicity Following Inhalation of Uranium Compounds for Two Years.- 4. Inhalation of UO2 for Five Years.- 5. Recent Inhalation Studies of Uranium Trioxide.- VIII. Distribution and Excretion of Uranium.- IX. Mechanisms of Uranium Action.- A. Entry of Uranium into the Body.- B. Transport of Uranium in Plasma.- C. Excretion of Uranium.- X. Toxic Action of Uranium on Kidney Structure and Function.- A. Morphologic Studies.- B. Functional Studies.- 1. Renal Clearance Studies.- 2. Proteinuria.- 3. Enzyme Studies.- C. Tolerance to Acute Uranium Poisoning.- XI. Attempted Prevention and Therapy of Uranium Poisoning.- References.- 4 Data on Man.- I. Introduction.- II. Planned Administrations of Uranium.- A. Intravenous Injection.- 1. The Rochester Intravenous Injection Experiment.- 2. The Boston Intravenous Injection Experiment.- 3. Experiments Using Uranium Injections to Evaluate Skeletal Metabolic Disorders.- 4. Interpretation of the Intravenous Experiments.- B. Oral Administration of Uranium.- 1. Use as a Therapeutic Agent.- 2. Experimental Ingestion by a Volunteer Subject.- 3. Hospital Study on Oral Absorption of Uranyl Nitrate.- 4. Interpretation of the Oral Experiments.- C. Inhalation of Uranium.- 1. Experimental Clearance of Uranium Dust from the Human Body.- 2. Interpretation of the Inhalation Experiment.- III. Occupational Exposure to Uranium.- A. Introductory Remarks.- B. General Industrial Exposure.- 1. “Soluble” and “Insoluble”.- 2. Biological Monitoring.- 3. Postmortem Data.- C. Uranium Hexafluoride.- 1. Normal Exposure.- 2. Acute Overexposure.- D. Less-Soluble Uranium Compounds.- 1. Occupational Exposures.- IV. Natural Background Levels of Natural Uranium.- A. Uranium in Soil and Plants.- B. Uranium in Water and Foodstuffs.- C. Uranium in Man.- D. Use of Background Uranium Data to Estimate Metabolic Parameters.- 1. Absorption.- 2. Rate Constant for Whole Body Loss.- References.- 5 Protection Criteria.- I. The History of Development of Protection Criteria for Uranium in Air.- A. Acceptable Limits to Human Exposure.- B. The Meaning of “Maximum Permissible”.- C. Towards an Occupational Air Standard for Natural Uranium.- 1. The Earliest Assessment at Oak Ridge (1947).- 2. The Emergency Guide at Rochester, N.Y. (1949).- 3. Early Rochester Results (1949).- 4. Recommendation of the Rochester Committee (1949).- 5. Recommendation of the Chalk River Conference (1949).- 6. The Tangled Reports of 1949.- 7. Recommendation of the Harriman Conference (1953).- D. Recommendation of the ICRP Committee II (1954, 1958).- E. Recommendation of the ACGIH (1957, 1968).- F. Other Deliberating and Authorizing Bodies.- II. Protection Criteria for Uranium in Drinking Water.- A. History of Recommended (MPC)ws.- B. The Limitation on Short-Term Intake.- III. The Calculation of the (MPC)a for Uranium According to Current ICRP-NCRP Practice.- A. Guiding Principles and Dose Units for Radioactive Nuclides.- B. Methods of Setting Limits where Chemical Toxicity is the Critical Endpoint.- 1. Alternative Approaches.- 2. Derivation of the (MPC)a for Soluble Natural Uranium.- 3. The Derivation of the (MPC)w for Natural Uranium.- Comment: Basis for Selection of 3 ?g per Gram Kidney as Permissible.- C. Method of Setting Limits when Radiation Injury is the Critical Endpoint.- 1. Derivation of (MPC)a for Insoluble Natural Uranium.- 2. Comment.- a) The Critical Organ.- b) Further Consideration of the Differences in the Experimental Animal Results and Experience with Occupationally Exposed Human Subjects.- c) The Lymph Nodes as a Critical Organ.- IV. Modification of the Occupational MPCs for Application to the General Public.- A. Lower Limits Recommended.- B. Basic Radiation Dose Limits and Related MPCs for the General Public.- 1. Individual.- 2. Population as a Whole.- 3. The Derived MPCs.- C. At what Numerical Size Does a Group Become a Population?.- D. Limits for Uranium in Environmental Air and Water.- 1. Soluble Natural Uranium Compounds.- 2. Insoluble Natural Uranium Compounds.- E. Comparison of Population MPCs and Present Environmental Levels.- 1. Uranium in the Environment.- 2. Uranium Production Waste Products.- V. Derived Occupational Limits for Personnel Monitoring.- A. Urinary Excretion Limits.- 1. General Remarks.- 2. Urinary Levels as an Environmental Control Index.- 3. Urinary Analysis as a Means of Detecting Unreported Accidents.- 4. The Use of Routine Urinary Uranium Data to Assess Individual Exposure..- B. Urinary Uranium Limits.- 1. Urinary Limit for Exposure to Soluble Forms of Uranium.- 2. Urinary Limit for Exposure to Insoluble Uranium Compounds.- C. The Urinary Limits Compared to Empirical Plant Findings.- VI. Practical Considerations Applicable to Industrial Conditions.- A. Selction of an Air Limit where Solubility of the Uranium Aerosol Cannot Be Stipulated.- B. Selection of an Air Limit when Uranium Aerosol is Known to Be Soluble.- C. Air Limits for Varying Degrees of Enrichment.- References.- 6 Environmental Monitoring and Personnel Protection in Uranium Processing.- I. Introduction.- II. Classification of Uranium.- III. Process Equipment Design.- A. Material Less than 5–8 Percent 235U.- B. Material Greater than 5–8 Percent 235U.- C. Special Materials.- IV. Environmental Monitoring.- A. General Air Sampling.- B. Diagnostic and Breathing-Zone Sampling.- C. Monitoring of Plant Releases.- 1. Stack Monitoring.- 2. Plant Effluent Monitoring.- D. Surface Contamination Sampling.- 1. Process Area Smears.- 2. Lunchroom and General Plant Area.- E. Personal Air Samplers.- F. Particle-Size Distribution in Processing Areas.- V. Personnel Monitoring.- A. Urine Analysis.- 1. Sample Type and Collection.- 2. Sampling Frequency.- B. Relationship of Uranium Air Concentrations and Urinary Uranium Excretion.- C. In vivo Monitoring.- D. Correlation of Uranium Urine Excretion Rate and in vivo Measurement Results.- E. Fecal Sampling.- F. Personnel Practices.- 1. Respirators.- 2. Protective Clothing.- 3. Personal Hygiene.- VI. Laboratory Analysis.- A. Air and Smear Samples.- B. Analysis of Soil and Plant Water Discharge.- C. Analysis of Urine Samples.- References.- 7 Uranium Mining Hazards.- I. Introduction.- A. Distribution of Uranium Ore Deposits.- B. Types of Mining Operations.- C. Constituents of Uranium Ores.- II. Health Hazards in Uranium Mining.- A. External Radiation.- B. Internal Radiation from Long-Lived Radioactive Elements.- C. Radon and Radon Daughters.- D. Other Health Hazards.- III. Experimental Exposures to Radon and Radon Daughters.- IV. Human Exposures to Radon and Radon Daughters.- V. Evaluation of Mine Atmospheres.- A. Measurement of Radon Concentration.- B. Measurements of Radon Daughters.- C. Measurements of Latent Alpha Energy Content.- D. Measurements of Condensation Nuclei.- E. Estimation of “Unattached Atoms”.- VI. Maximum Permissible Concentrations of Radon Daughters.- VII. Control of Radon Daughter Concentrations in Mines.- A. Mine Planning.- B. Reducing Radon Influx.- C. Removal of Radon and Radon Daughters by Ventilation.- D. Removal of Radon Daughters by Air-Cleaning.- References.- Plutonium.- Preface.- 8 Biomedical Aspects of Plutonium (Discovery, Development, Projections).- I. Foreword.- II. General Toxicology of Plutonium.- III Development of Biomedical Information on Plutonium.- A. Early Beginnings.- B. The “Plutonium Project” Years.- C. The Utah Project.- D. Inhalation Studies.- E. Information from Experience with Man.- F. Therapeutic Removal.- G. Work Abroad.- IV. Newer Uses of Plutonium.- V. Summary.- References.- 9 Chemical and Physical Properties of Plutonium.- I. Introduction.- A. The Position of Plutonium in the Periodic Table.- B. Electronic Structure.- C. Isotopes of Plutonium.- II. Plutonium and its Compounds.- A. Plutonium Metal.- B. Oxidation States.- C. Plutonium Compounds.- 1. Oxides.- 2. Halogen Compounds.- 3. Nitrates.- 4. Sulphates.- 5. Phosphates.- 6. Oxalates.- 7. Hydride, Carbides, Nitride, Silicides and Sulphides.- 8. Other Compounds.- III. Solution Chemistry of Plutonium.- A. Absorption Spectra of Plutonium.- B. Hydrolytic Reactions.- 1. Hydrolysis of Pu (IV).- 2. Hydrolysis of Pu (VI).- 3. Hydrolysis of Pu (III).- 4. Hydrolysis of Pu (V).- C. Plutonium Complexes.- 1. Complexes with Inorganic Anions.- 2. Acetate Complexes.- 3. Lactate Complexes.- 4. Citrate Complexes.- 5. Polyaminopolycarboxylic Acids.- 6. Complexes with 1:3 Diketones.- 7. Organophosphorus Complexes.- 8. Other Complexing Agents.- D. Oxidation States in Solution.- IV. Interaction of Plutonium with Proteins and Other Substances of Biological Interest.- A. Complexing with Plasma Proteins.- B. Binding to Ferritin.- C. Binding to Bone Proteins.- D. Binding to Other Proteins.- E. Binding to Other Substances.- References.- 10 Distribution, Excretion and Effects of Plutonium as a Bone-Seeker.- I. Introduction.- II. Metabolism of 239Pu with Special Reference to the Skeleton.- A. Species Differences.- B. Age Differences.- C. Routes of Entry with Special Reference to Skeletal Uptake.- 1. Intravenous.- 2. Gastrointestinal.- 3. Unbroken Skin.- 4. Intradermal.- 5. Subcutaneous.- 6. Intramuscular or Wound.- 7. Inhalation.- 8. Conclusions.- D. Plasma Transport.- E. Plasma Clearance.- F. Excretion.- G. Retention.- H. Problems of Estimating Skeletal Burden.- III. Other Plutonium Isotopes.- A. 238Pu.- 1. Intragastric.- 2. Intravenous and Intramuscular Injection.- 3. Inhalation.- B. Relative Toxicities of 238Pu and 239Pu.- C. Metabolic Patterns of 237Pu and 239Pu.- D. Conclusions.- IV. The Pattern of 239Pu Distribution in the Skeleton.- A. Bone Surfaces.- B. Bone Marrow.- 1. Distribution in Bone Marrow Following Intravenous Injection.- 2. Distribution in Bone Marrow Following Intramuscular Injection.- V. The Binding of Plutonium in Bone.- VI. Theory and Technique of Alpha Dosimetry with Particular Reference to the Skeleton.- A. Experimental Techniques.- 1. Macroscopic and Microscopic Measurements.- 2. Autoradiography.- 3. Microdensitometry.- 4. Solid State Track Detectors.- B. Plutonium Isotopes and Properties of Alpha Particle Irradiation.- 1. Plutonium Isotopes and the Decay of 239Pu.- 2. The Linear Energy Transfer, LET, and Stopping Power.- 3. The Nature of Alpha Particle Ionization.- 4. The Tissue Equivalent Sphere of Rossi and the Quantities Y and Z.- 5. The Irradiation of Cells by Alpha Particles.- 6. The Experimental Approach.- C. The Derivation of Formulae for the Calculation of Dose Rates.- 1. Introduction.- 2. The Point Source.- 3. The Uniform Volume Distribution.- 4. The Uniform Plane Source Normal to the Film.- 5. The Approximations Involved in Calculating Dose Rates at Bone Surfaces.- 6. The Poisson Distribution.- 7. The Relation Between Dose-rate and “Hit-Frequency”.- VII. Radiation Dose Measurements from Deposition of 239Pu in the Skeleton.- A. Introduction.- B. Bone Surfaces.- 1. Intravenous Injections.- a) Rats.- b) Dogs.- c) Rabbits.- d) Comparison of Different Animals.- 2. Intramuscular Injections.- a) Rabbits.- b) Bone Surfaces.- C. Marrow.- 1. Intravenous Injections.- 2. Intramuscular Injections.- D. Conclusion.- VIII. Effects of 239Pu Deposition in the Skeleton.- A. Carcinogenesis.- 1. Osteogenic Sarcoma.- a) Skeletal Site.- b) Microscopic Anatomy.- c) Relation of Bone Radiation Dose to Osteogenic Sarcoma.- 2. Cells at Carcinogenic Risk in Marrow.- a) Mesenchyme Tumours other than Leukaemia.- b) Leukaemia.- 3. Cells at Carcinogenic Risk in Epithelial Tissue.- B. Dysplasia.- 1. Bone.- a) Radiological Changes.- b) Histopathology.- 2. Marrow.- IX. Removal of Internally Deposited Plutonium from the Skeleton.- A. Anion Exchange Resins.- B. Colloidal Scavenging Agents.- C. Chelating Agents.- 1...