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Addendum to the Toxicological Profile for Arsenic

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Addendum to the Toxicological Profile for Arsenic ADDENDUM TO THE TOXICOLOGICAL PROFILE FOR ARSENIC Agency for Toxic Substances and Disease Registry Division of Toxicology and Human Health Sciences Atlanta, GA 30329-4027 February 2016 ARSENIC i CONTENTS LIST OF FIGURES ..................................................................................................................................... iii LIST OF TABLES ....................................................................................................................................... iv 3. HEALTH EFFECTS ................................................................................................................................ 1 3.1 INTRODUCTION ........................................................................................................................ 1 3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE ...................................... 2 3.2.1 Inhalation Exposure .............................................................................................................. 2 3.2.1.3 Immunological and Lymphoreticular Effects ............................................................... 2 3.2.2 Oral Exposure ....................................................................................................................... 3 3.2.2.1 Death ............................................................................................................................. 3 3.2.2.2 Systemic Effects ............................................................................................................ 3 3.2.2.3 Immunological and Lymphoreticular Effects ............................................................. 45 3.2.2.4 Neurological Effects ................................................................................................... 48 3.2.2.5 Reproductive Effects ................................................................................................... 52 3.2.2.6 Developmental Effects ................................................................................................ 58 3.2.2.7 Cancer ......................................................................................................................... 78 3.3 GENOTOXICITY ....................................................................................................................... 84 3.4 TOXICOKINETICS ................................................................................................................... 85 3.4.1 Absorption ........................................................................................................................... 85 3.4.1.2 Oral Exposure ............................................................................................................. 85 3.4.1.3 Dermal Exposure ......................................................................................................... 94 3.4.2 Distribution ......................................................................................................................... 94 3.4.2.1 Inhalation Exposure .................................................................................................... 94 3.4.3 Metabolism ......................................................................................................................... 94 3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models ........... 95 3.4.5.1 Summary of PBPK Models ......................................................................................... 95 3.4.5.2 Arsenic PBPK Model Comparison ............................................................................. 98 3.4.5.3 Discussion of Models .................................................................................................. 99 3.5 MECHANISMS OF ACTION .................................................................................................. 100 3.5.1 Pharmacokinetic Mechanisms ........................................................................................... 100 3.5.2 Mechanisms of Toxicity .................................................................................................... 100 3.7 CHILDREN’S SUSCEPTIBILITY .......................................................................................... 102 3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE .............................................. 103 4. CHEMICAL AND PHYSICAL INFORMATION .............................................................................. 103 5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL .......................................................... 103 5.1 PRODUCTION ......................................................................................................................... 103 5.2 IMPORT/EXPORT ................................................................................................................... 103 5.3 USE ........................................................................................................................................... 104 5.4 DISPOSAL ............................................................................................................................... 104 6. POTENTIAL FOR HUMAN EXPOSURE ......................................................................................... 105 6.1 OVERVIEW ............................................................................................................................. 105 6.2 RELEASES TO THE ENVIRONMENT ................................................................................. 105 6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT ................................ 105 6.4.1 Air ..................................................................................................................................... 105 ARSENIC ii 6.4.2 Water ................................................................................................................................. 105 6.4.3 Sediment and Soil ............................................................................................................. 111 6.4.4 Other Environmental Media .............................................................................................. 112 6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE ....................................... 118 6.6 EXPOSURES OF CHILDREN ................................................................................................ 156 6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ............................................. 158 6.8 ADEQUACY OF THE DATA BASE ...................................................................................... 159 6.8.1 Identification of Data Needs ............................................................................................. 159 6.8.2 Ongoing Studies ................................................................................................................ 159 7. ANALYTICAL METHODS................................................................................................................ 159 7.1 BIOLOGICAL SAMPLES ....................................................................................................... 159 7.2 ENVIRONMENTAL SAMPLES ............................................................................................. 160 8. REGULATIONS AND ADVISORIES ............................................................................................... 162 9. REFERENCES .................................................................................................................................... 167 ARSENIC iii LIST OF FIGURES 3-1. Flow- and Diffusion-Limited DMA(V) PBPK Model ....................................................................... 97 ARSENIC iv LIST OF TABLES 3-1. Respiratory Effects of Oral Exposure to Inorganic Arsenicals in Humans .......................................... 4 3-2. Cardiovascular Effects of Oral Exposure to Inorganic Arsenicals in Humans ................................... 13 3-3. Gastrointestinal Effects of Oral Exposure to Inorganic Arsenicals in Humans .................................. 30 3-4. Endocrine Effects of Oral Exposure to Inorganic Arsenicals in Humans .......................................... 33 3-5. Ocular Effects of Oral Exposure to Inorganic Arsenicals in Humans ................................................ 46 3-6. Neurological Effects of Oral Exposure to Inorganic Arsenicals in Humans ...................................... 49 3-7. Reproductive Effects of Oral Exposure to Inorganic Arsenicals in Humans ..................................... 53 3-8. Reproductive Effects of Oral Exposure to Inorganic Arsenicals in Animals ..................................... 54 3-9. Developmental Effects of Oral Exposure to Inorganic Arsenicals in Humans .................................. 59 3-10. Developmental Effects of Oral Exposure to Inorganic Arsenicals in Animals ................................ 76 3-11. Cancer in Humans Following In Utero and/or Early Life Exposure to Arsenic in Drinking Water ................................................................................................................................................ 80 3-12. Genotoxicity in Humans Exposed to Oral Arsenic ........................................................................... 86 3-13. Comparison of Major Features of PBPK Models for Arsenic .......................................................... 98 6-1. Speciation of Arsenic in U.S. Commercial Rice .............................................................................
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