Iodine, inorganic and soluble salts Evaluation of health hazards and proposal of a health-based quality criterion for drinking water Environmental Project No. 1533, 2014 Title: Editing: Iodine, inorganic and soluble salts Elsa Nielsen, Krestine Greve, John Christian Larsen, Otto Meyer, Kirstine Krogholm, Max Hansen Division of Toxicology and Risk Assessment National Food Institute, Technical University of Denmark Published by: The Danish Environmental Protection Agency Strandgade 29 1401 Copenhagen K Denmark www.mst.dk/english Year: ISBN no. Authored 2013. 978-87-93026-87-2 Published 2014. Disclaimer: When the occasion arises, the Danish Environmental Protection Agency will publish reports and papers concerning research and development projects within the environmental sector, financed by study grants provided by the Danish Environmental Protection Agency. It should be noted that such publications do not necessarily reflect the position or opinion of the Danish Environmental Protection Agency. However, publication does indicate that, in the opinion of the Danish Environmental Protection Agency, the content represents an important contribution to the debate surrounding Danish environmental policy. Sources must be acknowledged. 2 Iodine, inorganic and soluble salts Content CONTENT 3 PREFACE 5 1 GENERAL DESCRIPTION 6 1.1 IDENTITY 6 1.2 PRODUCTION AND USE 6 1.3 ENVIRONMENTAL OCCURRENCE AND FATE 7 1.3.1 Air 7 1.3.2 Water 7 1.3.3 Soil 8 1.3.4 Foodstuffs 10 1.3.5 Bioaccumulation 11 1.4 HUMAN EXPOSURE 11 2 TOXICOKINETICS 15 2.1 ABSORPTION 15 2.1.1 Oral intake 15 2.1.2 Dermal contact 16 2.2 DISTRIBUTION AND ELIMINATION 16 2.3 PHYSIOLOGICAL ROLE 17 2.4 MODE OF ACTION 18 3 HUMAN TOXICITY 20 3.1 SINGLE DOSE TOXICITY 21 3.2 IRRITATION 21 3.3 SENSITISATION 21 3.4 REPEATED DOSE TOXICITY 21 3.4.1 Experimental studies 22 3.4.2 Epidemiological studies 24 3.5 TOXICITY TO REPRODUCTION 30 3.6 MUTAGENIC AND GENOTOXIC EFFECTS 31 3.7 CARCINOGENIC EFFECTS 31 4 ANIMAL TOXICITY 32 4.1 SINGLE DOSE TOXICITY 32 4.2 IRRITATION 32 4.3 SENSITISATION 32 4.4 REPEATED DOSE TOXICITY 32 4.5 TOXICITY TO REPRODUCTION 32 4.6 MUTAGENIC AND GENOTOXIC EFFECTS 33 4.6.1 In vitro studies 33 4.6.2 In vivo studies 33 4.7 CARCINOGENIC EFFECTS 33 5 REGULATIONS 34 5.1 AMBIENT AIR 34 5.2 DRINKING WATER 34 5.3 SOIL 34 3 5.4 OCCUPATIONAL EXPOSURE LIMITS 34 5.5 CLASSIFICATION 34 5.6 IARC 34 5.7 WHO/FAO: JECFA 34 5.8 EFSA 35 5.9 US-EPA 35 5.10 ATSDR 35 6 SUMMARY AND EVALUATION 37 6.1 DESCRIPTION 37 6.2 ENVIRONMENT 37 6.3 HUMAN EXPOSURE 38 6.4 TOXICOKINETICS 38 6.5 PHYSIOLOGICAL ROLE 39 6.6 HUMAN TOXICITY 39 6.6.1 Single dose toxicity 40 6.6.2 Irritation 40 6.6.3 Sensitisation 40 6.6.4 Repeated dose toxicity 40 6.6.5 Toxicity to reproduction 42 6.6.6 Mutagenic and genotoxic effects 43 6.6.7 Carcinogenic effects 43 6.7 ANIMAL TOXICITY 43 6.8 EVALUATION 43 6.8.1 Critical effect and NOAEL 45 7 TDI AND QUALITY CRITERION 47 8 REFERENCES 48 4 Preface This report has been prepared by Elsa Nielsen, Krestine Greve, John Christian Larsen, Otto Meyer, Kirstine Krogholm and Max Hansen, Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark. The report has been elaborated according to the general practice laid down in the Danish EPA guidance document for the setting of health-based quality criteria for chemical substances in relation to soil, ambient air and drinking water. The report has been subjected to review and discussion and has been endorsed by a steering committee consisting of the following representatives from Danish authorities: • The Danish Nature Agency: Anne Christine Duer • The Danish Ministry of Food, Agriculture and Fisheries (The Faculty of Agricultural Sciences): Niels Henrik Spliid • The Danish Veterinary and Food Administration: Gudrun Hilbert • The National Board of Health, Denmark, medical officer of health: Lene Garsdal • Danish Regions: Arne Rokkjær, • The Danish Environmental Protection Agency: Katrine Smith, Poul Bo Larsen, Finn Pedersen, Jette Rud Heltved. 5 1 General description Iodine is a non-metallic element belonging to the halogen family in Group VIIA of the periodic table. Iodine can exist in several oxidation states: –1, 0, +1, +3, +5 and +7. Under normal environmental conditions, the -1, 0, and +5 oxidation states are - the most important. Iodine is found in nature as molecular iodine (I2), iodide (I ), or - iodate (IO3 ). There are 36 isotopes of iodine and 14 of these yield significant radiation. The only naturally occurring isotopes of iodine are the stable isotope 127I and the radioactive isotope 129I. In this evaluation only non-radioactive iodine is considered. Molecular iodine and water-soluble iodine salts release the iodide ion in contact with water. Thus, iodine occurs in water in the form of iodide (I-), which is largely oxidised to molecular iodine during water treatment. Molecular iodine as well as water-soluble iodine salts are rapidly converted into iodide in the gut following ingestion and this is efficiently absorbed throughout the gastrointestinal tract. Therefore, toxicological effects can be considered together for molecular iodine and water-soluble iodine salts to the extent that these effects are directly mediated by the iodide ion. This evaluation is limited to consider the toxicity of inorganic salts of the stable iodine (isotope 127I) from which the iodide ion can be liberated, as this form is the relevant one in relation to estimation of a health-based quality criterion in drinking water. This document is mainly based on evaluations prepared by ATSDR (2004), WHO (2003) and EFSA (2006). In this evaluation, the term “molecular iodine” is used to refer to I2 and the term “iodide” is used to refer to the anion I-. The term “iodine” is used in a generic sense and refers to the element in any form. For the purpose of comparison, concentrations and dose levels of the various iodide salts are expressed in terms of iodine equivalents (I) whenever possible. 1.1 Identity The identity and physico-chemical properties of molecular iodine and selected soluble inorganic iodine salts are presented in Table 1. 1.2 Production and use Approximately 54% of the iodine consumed in the world is obtained from Chile as a co-product from surface mineral deposits used to produce nitrate fertilizers and about 43% from brines processed in Japan, the United States and the former Soviet Union (ATSDR 2004). Iodine is used as an antiseptic for skin wounds, as a disinfecting agent in hospitals and laboratories, and for the emergency disinfection of drinking-water in the field. Iodide is used in pharmaceuticals and in photographic developing materials. (WHO 2003). 6 Table 1. Identity and chemical properties of molecular iodine and selected water soluble inorganic iodine salts (ATSDR 2004). Iodine Potassium Sodium Copper (I) Calcium iodide iodide iodide iodide Molecular formula I2 KI NaI CuI CaI2 Molecular weight 253.8 166.0 149.9 190.5 293.9 CAS-number 7553-56-2 7681-11-0 7681-82-5 7681-65-4 10102-68-8 Description Bluish- Colourless White Red-brown Yellow lumps or black or white crystals or powder or powder scales or crystals or granules crystals plates granules Melting point (°C) 113.6 680 651 588-606 740 Boiling point (°C) 185,2 1323 1304 ~1290 1100 Density (g/cm3) 4.93 3.12 3.67 5.63 - Water solubility 0.3 at 1430 at 2000 at 0.08 at 18°C Very soluble (g/l) 25°C 25°C 25°C 1.3 Environmental occurrence and fate Iodine is a naturally occurring constituent of the earth’s crust and is the least abundant of the halogen elements. The stable iodine isotope (127I) is ubiquitous throughout the earth’s surface in igneous rocks and soils, most commonly as impurities in saltpetre and natural brines. The concentration of 127I in the earth’s crust is approximately 0.5 mg/kg. (ATSDR 2004). Releases of iodine into the environment occur from both natural sources and human activity. The natural sources include volatilisation of iodine from the oceans, weathering of rocks, and volcanic activity. Sources of iodine from human activities include release of iodine from waste stream effluent from municipal plants, and combustion of waste and fossil fuels. (ATSDR 2004). 1.3.1 Air Iodine enters the atmosphere mainly through volatilisation of methyl iodide and, to a lesser extent, molecular iodine from the ocean surface. In the atmosphere, iodine undergoes extensive photochemical changes and can exist as gaseous inorganic, gaseous organic, or particulate forms. These forms have an average residency time in the atmosphere of 10, 18, and 14 days, respectively. (ATSDR 2004). The gaseous inorganic and particulate forms of iodine are precipitated from the atmosphere through wet (rain, sleet, and snow) and dry (gravitational settling and wind turbulence) deposition processes. If precipitation occurs over land, iodine will be deposited onto plant surfaces or soil surfaces, or into surface waters. (ATSDR 2004). Atmospheric iodine is present at levels of 3-50 ng/m3, the average global value being 10-20 ng/m3 (EFSA 2006, ATSDR 2004). 1.3.2 Water Iodine occurs naturally in water in the form of iodide, which is largely oxidised to iodine during water treatment (WHO 2003). 7 Introduction of iodine into surface waters and groundwater occurs predominately through rainwater for non-coastal land regions and the combination of rainwater and ocean spray in coastal regions. The iodine in rainwater is derived from the volatilisation of iodine from the oceans to the atmosphere.