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Safety Evaluation of Certain Contaminants in Food WHO FOOD Safety evaluation of ADDITIVES certain contaminants in SERIES: 63 food FAO JECFA MONOGRAPHS 8 Prepared by the Seventy-second meeting of the Joint FAO/ WHO Expert Committee on Food Additives (JECFA) ARSENIC (addendum) (pages 153 – 316) World Health Organization, Geneva, 2011 Food and Agriculture Organization of the United Nations, Rome, 2011 ARSENIC (addendum) First draft prepared by D.J. Benford,1 J. Alexander,2 J. Baines,3 D.C. Bellinger,4 C. Carrington,5 V.A. Devesa i Peréz,6 J. Duxbury,7 J. Fawell,8 K. Hailemariam,5 R. Montoro,6 J. Ng,9 W. Slob,10 D. Veléz,6 J.W. Yager11 and Y. Zang5 1 Food Standards Agency, London, England 2 Norwegian Institute of Public Health, Oslo, Norway 3 Population Health Division, Department of Health and Ageing, Canberra, Australia 4 Harvard Medical School Children’s Hospital, Boston, MA, United States of America (USA) 5 Center for Food Safety and Applied Nutrition, Food and Drug Administration, College Park, MD, USA 6 Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Sapin 7 Cornell University, Ithaca, NY, USA 8 Flackwell Heath, Buckinghamshire, England 9 National Research Centre for Environmental Toxicology, The University of Queensland, Brisbane, Queensland, Australia, & Cooperative Research Centre for Contamination Assessment and Remediation of the Environment, Adelaide, South Australia, Australia 10 National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands 11 University of New Mexico, Albuquerque, NM, USA 1. Explanation............................................................................. 155 2. Biological data........................................................................ 157 2.1 Biochemical aspects......................................................... 157 2.1.1 Absorption, distribution and excretion..................... 157 2.1.2 Biotransformation.................................................... 159 2.1.3 Effects on enzymes and other biochemical parameters ............................................................. 160 2.2 Toxicological studies ....................................................... 161 2.2.1 Acute toxicity........................................................... 161 2.2.2 Short-term studies of toxicity................................... 162 2.2.3 Long-term studies of toxicity and carcinogenicity........................................................ 163 2.2.4 Genotoxicity............................................................ 166 2.2.5 Reproductive and developmental toxicity................ 167 2.2.6 Special studies........................................................ 169 2.3 Observations in humans................................................... 172 2.3.1 Biomarkers of exposure ......................................... 172 2.3.2 Biomarkers of effect ............................................... 174 2.3.3 Clinical observations .............................................. 175 2.3.4 Epidemiological studies........................................... 175 - 153 - 154 ARSENIC (addendum) 3. Analytical methods.................................................................. 204 3.1 Sample preparation for total arsenic determination......... 204 3.2 Sample preparation for arsenic species determination ................................................................... 205 3.3 Separation of arsenic species ......................................... 206 3.4 Detection systems ........................................................... 207 4. Effects of processing.............................................................. 208 5. Prevention and control............................................................ 210 5.1 Strategies for reducing arsenic exposure from water....... 211 5.2 Strategies for reducing arsenic exposure from foods....... 212 5.2.1 Reducing arsenic uptake into food crops ............... 213 5.2.2 Increasing the proportion of organic arsenic in food crops....................................................................... 215 5.2.3 Reducing the arsenic content of foods by preparation or cooking methods ............................. 218 6. Levels and patterns of contamination in food commodities........................................................................... 219 6.1 Arsenic content of food..................................................... 219 6.2 Occurrence of arsenic in water ........................................ 223 7. Food consumption and dietary exposure estimates............... 225 7.1 Arsenic levels used in dietary exposure estimates.......... 226 7.1.1 Conversion factors from total arsenic to inorganic arsenic..................................................................... 234 7.2 Dietary exposure estimates.............................................. 234 7.2.1 Estimates of total arsenic dietary exposure............ 234 7.2.2 Contributions to total arsenic dietary exposure ...... 242 7.2.3 Estimates of inorganic arsenic dietary exposure ................................................................ 246 7.2.4 Contributions to inorganic arsenic dietary exposure ................................................................ 258 8. Dose–response analysis and estimation of carcinogenic risk.......................................................................................... 259 8.1 Identification of key data for risk assessment................... 259 8.1.1 Pivotal data from biochemical and toxicological studies..................................................................... 259 8.1.2 Pivotal data from human clinical/epidemiological studies..................................................................... 260 8.2 General modelling considerations.................................... 263 8.2.1 Dose–response modelling and BMD calculations............................................................. 263 8.2.2 Selection of data..................................................... 263 8.3 Benchmark dose estimates.............................................. 266 8.3.1 Chen et al. (2010b), lung cancer............................. 266 8.3.2 Chen et al. (2010b), lung cancer, sensitivity analyses.................................................................. 270 8.3.3 Chen et al. (2010a), urinary tract cancer................. 271 8.3.4 Ahsan et al. (2006), skin lesions............................. 271 8.3.5 Ahsan et al. (2006), skin lesions, sensitivity analyses ................................................................. 274 8.3.6 Rahman et al. (2006), skin lesions.......................... 275 9. Comments ............................................................................. 276 9.1 Absorption, distribution, metabolism and excretion.......... 276 ARSENIC (addendum) 155 9.2 Toxicological data............................................................. 277 9.3 Observations in humans................................................... 278 9.4 Analytical methods .......................................................... 279 9.5 Effects of processing........................................................ 280 9.6 Prevention and control..................................................... 280 9.7 Levels and patterns of contamination in food commodities..................................................................... 281 9.8 Food consumption and dietary exposure assessment...................................................................... 282 9.9 Dose–response analysis ................................................. 285 10. Evaluation............................................................................. 287 10.1 Recommendation .......................................................... 288 11. References .......................................................................... 288 1. EXPLANATION Arsenic is a metalloid that occurs in different inorganic and organic forms, which are found in the environment both from natural occurrence and from anthropogenic activity. Arsenic was previously evaluated by the Committee at its tenth, twenty-seventh and thirty-third meetings (Annex 1, references 13, 63 and 84). At its twenty-seventh meeting (in 1983), it was concluded that “on the basis of the data available the Committee could arrive at only an estimate of 0.002 mg/kg b.w. as a provisional maximum tolerable daily intake for ingested inorganic arsenic; no figure could be arrived at for organic arsenicals in food” (Annex 1, reference 63). This was based on the observation that arsenicism can be associated with water supplies containing an upper arsenic concentration of 1 mg/l or greater and that a concentration of 0.1 mg/l may give rise to presumptive signs of toxicity. Assuming a daily water consumption of 1.5 litres, the Committee concluded that inorganic arsenic intakes of 1.5 mg/day were likely to result in chronic arsenic toxicity and that daily intakes of 0.15 mg may also be toxic in the long term to some individuals. The Committee noted that the International Programme on Chemical Safety (IPCS) had estimated that an arsenic concentration of 0.2 mg/l in drinking- water would lead to a 5% lifetime risk of skin cancer, but that skin cancer did not occur in the absence of other toxic effects due to arsenic. The Committee also noted a need for information on: • arsenic accumulation in humans exposed to various forms of arsenic in the diet and drinking-water; • the identification, absorption, elimination and toxicity of arsenic compounds in food, with particular reference
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