[Tentative translation] Risk Assessment Report Arsenic in foods (Chemicals and Contaminants) Food Safety Commission Japan (FSCJ) October 2013 0 [Tentative translation] Contents Page Chronology of Discussions .................................................................................................... 3 List of members of the Food Safety Commission .................................................................. 3 List of members of the EPCC, the Food Safety Commission ................................................ 4 Executive summary ................................................................................................................ 6 I. Background ......................................................................................................................... 9 II. Outline of the Substances under Assessment .................................................................... 9 1. Physiochemical properties ......................................................................................... 9 (1) Metallic arsenic ................................................................................................... 9 (2) Inorganic arsenic compounds ........................................................................... 10 (3) Organic arsenic compounds .............................................................................. 12 (4) Analytical methods for arsenic ......................................................................... 16 2. Major use and production ........................................................................................ 22 3. Distribution and dynamics in the environment ....................................................... 23 (1) Air ...................................................................................................................... 23 (2) Soil ..................................................................................................................... 23 (3) The waters, bottom sediment, ground water ...................................................... 24 (4) House dust .......................................................................................................... 25 (5) Arsenic circulation in ecosystem ....................................................................... 26 4. Current regulations and others ................................................................................ 29 III. Exposure in human ......................................................................................................... 32 1. Oral exposure .......................................................................................................... 32 (1) Exposure from food ............................................................................................ 32 (2) Estimation of oral exposure ................................................................................ 40 2. Inhalation exposure ................................................................................................. 42 IV. Summary of safety data .................................................................................................. 44 1. Pharmacokinetics .................................................................................................... 44 (1) Absorption ......................................................................................................... 44 (2) Distribution ........................................................................................................ 45 (3) Metabolism ........................................................................................................ 47 (4) Excretion ............................................................................................................ 51 2. Effect of inorganic arsenic compounds ................................................................... 53 (1) Effect in humans ................................................................................................ 53 (2) Effect on experimental animals ......................................................................... 73 3. Effect of organic arsenic compounds ...................................................................... 92 (1) Effect on humans ............................................................................................... 92 (2) Effect on experimental animals ......................................................................... 94 4. Effect of synthetic organic arsenic compounds ..................................................... 101 (1) Effect on humans ............................................................................................. 101 (2) Effect on experimental animals ....................................................................... 102 5. Genotoxicity .......................................................................................................... 105 (1) Effect on humans ................................................................................................ 105 (2) Effect on experimental animals .......................................................................... 113 6. Mechanism of toxicity ........................................................................................... 136 (1) Gene mutation, chromosome aberration, DNA damage .................................. 136 (2) Changes in DNA repair ................................................................................... 138 1 [Tentative translation] (3) Changes in DNA methylation .......................................................................... 139 (4) Cell transformation .......................................................................................... 140 (5) Changes in cell proliferation ............................................................................ 140 (6) Changes in cellular signal transduction ........................................................... 140 (7) Changes in binding to steroid receptors and gene expression ......................... 141 (8) Gene amplification .......................................................................................... 141 (9) Acceleration of mutation and genotoxicity ..................................................... 141 V. Evaluation in international organizations ...................................................................... 142 1. International Agency for Research on Cancer (IARC) ....................................... 142 2. FAO/WHO Joint Expert Committee on Food Additives (JECFA) ..................... 143 3. World Health Organization (WHO) Guidelines for drinking-water ................... 144 4. United States Environmental Protection Agency (EPA) ..................................... 145 (1) Inorganic arsenic ................................................................................................ 145 (2) Organic arsenic .................................................................................................. 146 5. European Food Safety Authority (EFSA) ............................................................. 147 6. Japan ...................................................................................................................... 149 (1) The Revision of Drinking-water Quality Standards, the Health Science Council, Ministry of Health, Labour and Welfare ................................................................................ 149 (2) New Energy and Industrial Technology Development Organization (NEDO) ................................................................................................................................................ 149 (3) Health Risk Subcommittee, Atmospheric Environment Committee, the Central Environment Council, Ministry of the Environment (reference) ......................................... 150 (4) Committee for Recommendation of Occupational Exposure Limits, Japan Society for Occupational Health (reference) ........................................................................ 150 VI. Risk Assessment (extracted from Part III of the original risk assessment report) ..... 151 1. Pharmacokinetics .................................................................................................. 151 2. Toxicity ................................................................................................................. 152 3. Exposure level ....................................................................................................... 153 4. Dose-dependent assessment .................................................................................. 153 (1) Applying the NOAEL/LOAEL method and BMD method ............................. 153 (2) Non-carcinogenic effects ................................................................................. 158 (3) Carcinogenic effects ........................................................................................ 159 (4) Estimation of daily intake of inorganic arsenic in the area with contaminated drinking-water ........................................................................................................................ 163 5. Summary and issues to be solved .......................................................................... 177 <Appendix: Abbrebiation.> ............................................................................................... 179 <References> .....................................................................................................................