Iodine as a

drinking-water disinfectant
 Iodine as a drinking-water disinfectant

Alternative drinking-water disinfectants: iodine

ISBN 978-92-4-151369-2

© World Health Organization 2018

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 Iodine as a drinking-water disinfectant

Acknowledgements
The World Health Organization (WHO) wishes to express its appreciation to all whose efforts made
the development and publication of this document possible.

The lead authors of this publication were:

 Ruth Bevan, formerly Cranfield University (currently IEH Consulting Ltd.), United Kingdom
(UK)
 Andreas Nocker, formerly Cranfield University, UK (currently IWW Water Centre,
Germany)

The following experts contributed to the development of this document through participation in
meetings, peer review and/or provision of insights and text:

 Mari Asami, National Institute of Public Health, Japan

 Virunha Bhat, NSF International, United States of America (USA)
 Sophie Boisson, WHO, Switzerland
 Joe Brown, Consultant, Georgia Institute of Technology, USA
 Enrique Calderon, Agua y Saneamientos Argentinos, Argentina
 Philip Callan, Consultant, Australia
 Joesph Cotruvo, Joseph Cotruvo and Associates LLC, USA
 David Cunliffe, Department of Health South Australia, Australia
 Lesley D’Anglada, United States Environmental Protection Agency (USEPA), USA
 Ana Maria de Roda Husman, National Institute of Public Health and the Environment
(RIVM), the Netherlands
 Alexander Eckhardt, Umweltbundesamt (Federal Environmental Agency), Germany
 John Fawell, Visiting Professor, Cranfield University, UK
 Lorna Fewtrell, Aberystwyth University, UK
 Charles Gerba, University of Arizona, USA
 Paul Hunter, University of East Anglia, UK
 Jane MacAulay, Health Canada, Canada
 Batsirai Majuru, WHO, Switzerland
 Peter Marsden, Drinking Water Inspectorate, UK
 Gertjan Medema, KWR Watercycle Research Institute and Delft University of Technology,
the Netherlands
 Bette Meek, University of Ottawa, Canada
 Maggie Montgomery, WHO, Switzerland
 Choon Nam Ong, National University of Singapore, Singapore
 Santhini Ramasamy, USEPA, USA
 Stig Regli, USEPA, USA
 William Robertson, Watermicrobe Consultancy, Canada
 Lisa Rogers, WHO, Switzerland
 Shane Snyder, University of Arizona, USA
 Mark Sobsey, University of North Carolina at Chapel Hill, USA
 Rachid Wahabi, Ministry of Health, Morocco

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 Iodine as a drinking-water disinfectant

 Richard Weisman, USEPA, USA

Jennifer De France (WHO, Switzerland) coordinated the development of this work while strategic
direction was provided by Bruce Gordon (WHO, Switzerland).
Financial support from the Department for International Development, UK; the Ministry of Health,
Labour and Welfare, Japan; and the Public Utilities Board, the National Water Agency, a statutory
board under the Ministry of Environment and Water Resources, Singapore, is gratefully
acknowledged.

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 Iodine as a drinking-water disinfectant

Table of Contents
List of abbreviations and terms used in the document .......................................................................... vii
1. Introduction ............................................................................................................................................. 1
2. Disinfection characteristics and efficacy ............................................................................................... 2
2.1 Chemistry basics ................................................................................................................................. 2
2.1.1 Water solubility, taste and odour ................................................................................................. 2
2.1.2 Chemical speciation of iodine in water and corresponding disinfection powers ......................... 2
2.1.2.1 Effect of pH........................................................................................................................... 4
2.1.2.2 Effect of temperature ............................................................................................................ 6
2.2 Efficacy of iodine................................................................................................................................ 6
2.2.1 Bactericidal efficacy of iodine ..................................................................................................... 6
2.2.2 Disinfection in the presence of turbidity ...................................................................................... 7
2.2.3 Iodine-based disinfection products .............................................................................................. 8
2.2.3.1 Iodine solutions ..................................................................................................................... 8
2.2.3.2 Resins .................................................................................................................................... 9
2.2.4 Comparison of efficacy with chlorine ........................................................................................ 11
2.2.5 World Health Organization International Scheme to Evaluate Household Water Treatment
Technologies ....................................................................................................................................... 12
3. Safety and toxicity of iodine ................................................................................................................. 14
3.1 Human exposure ............................................................................................................................... 14
3.2 Guideline values................................................................................................................................ 15
3.2.1. WHO Guidelines for Drinking-water Quality........................................................................... 15
3.2.2 Other values ............................................................................................................................... 15
3.3 Human toxicity data .......................................................................................................................... 17
3.3.1 Toxicokinetics ............................................................................................................................ 17
3.3.1.1 Absorption........................................................................................................................... 17
3.3.1.2 Distribution ......................................................................................................................... 17
3.3.1.3 Metabolism ......................................................................................................................... 17
3.3.1.4 Elimination .......................................................................................................................... 18
3.3.2 Acute toxicity ............................................................................................................................. 18
3.3.3 Repeat dose toxicity ................................................................................................................... 18
3.3.3.1 Systemic effects .................................................................................................................. 18

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 Iodine as a drinking-water disinfectant

3.3.3.2 Neurotoxicity ...................................................................................................................... 20

3.3.3.3 Reproductive and developmental toxicity ........................................................................... 21
3.3.3.4 Immunotoxicity ................................................................................................................... 21
3.3.3.5 Genotoxicity ........................................................................................................................ 21
3.3.3.6 Carcinogenicity ................................................................................................................... 21
3.4 Animal toxicity studies ..................................................................................................................... 22
3.4.1 Toxicokinetics ............................................................................................................................ 22
3.4.2 Acute toxicity ............................................................................................................................. 22
3.4.3 Repeat dose toxicity ................................................................................................................... 22
3.4.3.1 Systemic toxicity ................................................................................................................. 22
3.4.3.2 Neurotoxicity ...................................................................................................................... 23
3.4.3.3 Reproductive and developmental toxicity ........................................................................... 23
3.4.3.4 Immunotoxicity ................................................................................................................... 24
3.4.3.5 Genotoxicity ........................................................................................................................ 24
3.4.3.6 Carcinogenicity ................................................................................................................... 24
3.4.4 In vitro toxicity studies .............................................................................................................. 24
3.5 Vulnerable populations ..................................................................................................................... 24
3.6 Toxicity of iodinated disinfection by-products ................................................................................. 25
3.6.1 Formation and occurrence of iodinated disinfection by-products .............................................. 25
3.6.2 Toxicological evaluations of iodinated disinfection by-products .............................................. 26
3.7 Summary ........................................................................................................................................... 28
4. Environmental considerations ............................................................................................................. 30
5. Discussion and conclusions................................................................................................................... 31
6. References .............................................................................................................................................. 34

Appendix A: Methodology ....................................................................................................................... 42

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 Iodine as a drinking-water disinfectant

List of abbreviations and terms used in the document

AI adequate intake

bw body weight

Ct product of disinfectant concentration and contact time

DBP disinfection by-product

GI gastrointestinal

HAV hepatitis A virus

HOCl hypochlorous acid

HIO hypoiodous acid

HWT household water treatment

I2 elemental iodine

IO3- iodate

I- iodide

NOAEL no-observed-adverse-effect level

NTU nephelometric turbidity units

OI- hypoiodite

PBI protein bound iodine

POU point-of-use

PPM parts per million

T4 thyroxine

T3 triiodothyronine

THM trihalomethane

TRH thyrotropin releasing hormone

TSH thyroid stimulating hormone

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 Iodine as a drinking-water disinfectant

UL tolerable upper intake limit

UK United Kingdom

USA United States of America

USEPA United States Environmental Protection Agency

WHO World Health Organization

viii
 Iodine as a drinking-water disinfectant

1. Introduction
Disinfection of water has greatly contributed to reducing risks to public health from microbiologically-
contaminated drinking-water.

Over the centuries numerous water disinfection techniques have been developed that are used in a wide
range of applications ranging from large and small public drinking-water treatment plants to point-of-
entry and point-of-use (POU) treatment devices. 1 Chlorine has been used for more than 100 years and
several other disinfectants have been studied extensively, but in many cases, questions remain with
respect to optimization of biocidal effectiveness under a range of conditions (i.e. efficacy), the chemistry
of the formation and toxicological significance of disinfection by-products (DBPs), interactions with
other water constituents, and the effectiveness and toxicology of disinfectant residuals. Most chemical
disinfectants can react with natural organic matter or breakdown to produce unwanted by-products. Many
newer products and applications are being developed and marketed for use, particularly in developing
countries, and even more unanswered questions exist about some of those products, including efficacy
and DBP formation.

Iodine is an essential nutrient. In addition, it has been used generally as an antiseptic for skin wounds, as a
disinfecting agent in hospitals and laboratories, and in the production of pharmaceuticals. In terms of the
disinfection of drinking-water, iodine is commonly used in the form of tablets or solutions during
emergencies and by travellers (Ongerth et al., 1989; Backer & Hollowell, 2000). At regular intervals,
there is renewed interest in the use of iodine as an alternative disinfectant to chlorine (and other
disinfectants) for drinking-water.

Iodine-based disinfection of water has a long history: iodine in concentrations between 2.5–7 mg/L
(equivalent to parts per million [ppm]) has been used for potable water treatment since the early 1900s,
especially for military operations (Hitchens, 1922; Vergnoux, 1915). Tablet formulations have been used
since the 1940s to ensure the microbiological safety of drinking-water for military personnel deployed in
the field (Chang & Morris, 1953). Also, in more recent times, iodine (and bromine) has become attractive
for particular applications. Elemental iodine is used, for example, as a drinking-water disinfectant aboard
space vessels at a residual concentration of approximately 2 ppm (Atwater et al., 1996). The more general
use of iodine is impeded, however, by the potential for excess iodine intake, cost and the possibility of the
formation of toxic DBPs.

The emphasis of this literature review is to evaluate available evidence on the efficacy and toxicity of
iodine as a water disinfectant. Information included in this review was initially obtained using a targeted
literature search strategy, with inclusion dates up to November 2013 and further “ad-hoc” searches were
carried out up to the closing date for public review (16 December 2016). Additional details of the search
strategy are included in Appendix 1.

1
Point-of-use devices treat only the water intended for direct consumption (drinking and cooking), typically at a single tap or
limited number of taps, while point-of-entry treatment devices are typically installed to treat all water entering a single home,
business, school, or facility.

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 Iodine as a drinking-water disinfectant

2. Disinfection characteristics and efficacy

2.1 Chemistry basics
Iodine, chlorine, bromine and fluorine belong to the halogen group of elements in the periodic table. All
of the halogens share the common property of being oxidants with seven electrons in their outer shell. As
oxidizing agents, halogens accept an electron to become the analogous halide ion. Different halogens vary
in their oxidation potential and the halogen with the strongest oxidative power is fluorine, followed by
chlorine, bromine, and iodine. Their reactivities are directly correlated with their electronegativities,
which are as follows (based on the Pauling nomenclature of electronegativity values): 2

fluorine (3.98) > chlorine (3.16) > bromine (2.96) > iodine (2.66).

The reactivities of the given halogens therefore decreases from left to right. Nevertheless, the usefulness
of a particular halogen as a disinfectant is determined not only by its reactivity, but also by its selectivity,
chemical stability and other factors including the potential to form by-products. Fluorine, the most
reactive of all elements of the periodic table, is so unstable that it reacts with surrounding water molecules
in a violent reaction forming hydrogen fluoride and oxygen. The reactivity of other halogens is more
selective, making them more suitable for practical applications. Among the three halogens used for
disinfection purposes (chlorine, iodine and bromine), iodine has the highest atomic weight and is the only
one to exist as a solid at room temperature.

2.1.1 Water solubility, taste and odour

Elemental iodine is less soluble in water than chlorine or bromine. Water solubility depends on pH and
temperature and is reported to be 0.03 mg/L at 20 oC, 0.78 mg/L at 50 oC and 4.45 mg/L at 100 oC (West,
1984). A saturated aqueous solution of iodine can be produced by passing water through a column of
crystalline iodine. The iodine concentration achieved will be approximately 200 mg/L at 10 oC and 400
mg/L at 30 oC (Chang, 1968). This concentrated solution can be diluted to achieve the desired
concentration of iodine.

Free halogen residuals usually produce tastes and odours in potable water. Bryan et al. (1973) compared
taste threshold determinations of chlorine, iodine and bromine residuals in water. The threshold taste
values for chlorine residuals varied with pH: 0.075 mg/L at pH 5.0; 0.156 mg/L at pH 7.0; and 0.450
mg/L at pH 9.0. In contrast, threshold taste values for iodine did not vary appreciably with pH, ranging
from 0.147 to 0.204 mg/L. In contrast to chlorine, which has a high vapour pressure and readily
volatilizes, especially in the presence of sunlight or higher temperatures, iodine has a low vapour pressure
resulting in little loss by volatilization (Black et al., 1970).

2.1.2 Chemical speciation of iodine in water and corresponding disinfection powers

Once elemental iodine (I2) is added to water, it hydrolyses in a pH-dependent manner to form hypoiodous
acid (HIO) and iodide (I-). The overall stoichiometry of iodine hydrolysis between pH 2 and 7 is given
below; for a more detailed description of iodine hydrolysis, the reader is referred to Lengyel et al. (1993):

2
The Pauling scale is a dimensionless relative quantity that describes the electronegativity of an atom in the periodic table.

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 Iodine as a drinking-water disinfectant

I2 + H2O ↔ HIO + I- + H+

Similar to hypochlorous acid (HOCl), hypoiodous acid can deprotonate to form hypoiodite (OI-)
according to the following general reaction:

HIO ↔ H+ + OI-

The different chemical species of iodine vary in their disinfection power. The active disinfectants are
elemental iodine and hypoiodous acid (Backer & Hollowell, 2000). Other species including iodide, iodate
(IO3-) and hypoiodite have mild or little antimicrobial activity (Chang, 1958). Comparing the two
disinfection-active chemical species, the oxidizing power of hypoiodous acid is nearly twice that of
elemental iodine (West, 1984). A comparison of oxidizing potentials with the equivalent chlorine species
is shown in Table 1.

Table 1: Comparison of oxidizing potentials of iodine and chlorine species (West, 1984)

Chemical species Oxidizing potential (in volts)

I2 0.535
HIO 0.987
Cl2 1.358
HOCl 1.482
Cl2–chlorine

The disinfection efficacy of the different chemical species depends not only on oxidizing potential, but
also on penetration power. Elemental iodine has higher penetrating power than hypoiodous acid (White,
1992).

A comprehensive study of disinfection efficacy was performed by Chang & Morris (1953). Iodine
concentrations in the range 5–10 ppm were found to be effective against different types of
microorganisms within 10 min at room temperature. Organisms tested included enteric bacteria, amoebic
cysts, cercariae, leptospira and viruses. Overall, different classes of microorganisms have different
susceptibilities to iodine: vegetative bacteria tend to be most sensitive, whereas viruses have an
intermediate sensitivity and protozoa tend to be more resistant (Backer & Hollowell, 2000). Moreover,
elemental iodine and hypoiodous acid contribute to different extents to the disinfection efficacy against
different microbes. Chemical speciation is highly pH dependent (addressed in the next section).
Disinfection sometimes follows first-order kinetics with the primary determinants of effectiveness being
disinfectant concentration and time of exposure of the microorganism (expressed as Ct in mg·min/L i.e.
the product of disinfectant concentration (C in mg/L) and contact time (t in min). Departures from first-

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 Iodine as a drinking-water disinfectant

order kinetics can occur due to such phenomena as declines in iodine concentration over time, microbial
aggregation and microbial protection by other particles.

2.1.2.1 Effect of pH
Both the hydrolysis and the subsequent equilibrium between elemental iodine and hypoiodous acid are
pH-dependent, but the effect is not as pronounced as with chlorine. Table 2 shows the proportions of
elemental iodine, hypoiodous acid and hypoiodite for a pH range between pH 5 and 9, in comparison with
the chlorine equivalents.

Table 2: Effect of pH on the speciation of iodine and chlorine (0.5% titratable iodine)

pH Iodine Chorine

I2 (%) HIO (%) OI- (%) Cl2 (%) HOCl (%) OCl- (%)

5 99 1 0 0.5 99.5 0
6 90 10 0 0 99.5 0.5
7 52 48 0 0 96.5 3.5
8 12 88 0.005 0 21.5 78.5
9 - - - 0 1 99
-
Cl2–chlorine; OCl –hypochlorite
Adapted from Chang (1958), Black et al. (1970) and Ellis & van Vree (1989).

Higher pH results in a progressive decline in elemental iodine with a shift in the equilibrium toward
hypoiodous acid. As the active disinfectants are elemental iodine and hypoiodous acid, to use iodine most
effectively as a disinfectant, the pH should be near neutral to mildly alkaline (pH 7–7.5) to allow adequate
levels of both elemental iodine and hypoiodous acid (Table 2). At ≥ pH 8.0, hypoiodous acid was reported
to be unstable and to slowly decompose into iodate and iodide (Ellis & van Vree, 1989). However, in the
absence of a stronger oxidant such as chlorine, iodate formation does not occur readily (Black et al.,
1970). More detailed information about speciation and its pH dependence is available in Gottardi (1999).
Overall, the disinfection effectiveness of iodine is not as heavily influenced by pH as chlorine is.
Hypochlorite formation increases at values > pH 7. Strong evidence has been provided that hypochlorite
has less disinfection power that can be influenced by concentrations of anions, such as sodium and
potassium (Chang & Morris, 1953; Keirn & Putnam, 1968; Haas et al., 1986; Jensen et al., 1980).

The progressive decline of free iodine residual and increasing proportion of hypoiodous acid with
increasing pH also has fundamental consequences for the disinfection power of iodine. Different effects
occur along this gradient and different iodine species have different disinfection efficacies for different
groups of microbes (Ellis et al., 1993). In generalized terms, elemental iodine is primarily effective
against bacterial spores and protozoan cysts, whereas hypoiodous acid is known to be an effective

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 Iodine as a drinking-water disinfectant

bactericide and virucide (Ellis et al., 1993). For example, Chang (1966) reported elemental iodine to be 2–
3 times more effective against Entamoeba histolytica cysts than hypoiodous acid, whereas hypoiodous
acid was found to be approximately 40 times more effective than elemental iodine against viruses.
Hypoiodous acid also had greater germicidal activity against vegetative bacteria than elemental iodine
(e.g. hypoiodous acid was found 3–4 times more effective than elemental iodine against Escherichia coli).

The effect of pH on speciation of iodine and the resulting effect on disinfection efficacy is exemplified in
a study by Taylor & Butler (1982). The authors reported that iodine was more effective against poliovirus
at pH 9 than at lower pH values, probably due to the fact that at this pH most iodine will exist in the form
of hypoiodous acid, which has greater virucidal activity than elemental iodine (Chang, 1966). The
virucidal efficacy of hypoiodous acid and elemental iodine was reported to be respectively 4–5 times and
200 times less than hypochlorous acid (Clarke et al., 1964).

As the prevalent iodine species varies with pH, the most suitable pH range for the disinfection of different
microbial groups will also vary. Overall trends in disinfection power of the various iodine species for
different groups of microorganisms are summarised in Table 3 below.

Table 3: Trends in disinfection power for different iodine species when applied to different
microbial groups and pH range where the most effective disinfectant prevails (Taylor and Butler,
1982)

Microbial group Disinfection effectiveness of Suitable pH range for

different iodine species disinfection

Bacteria (vegetative) HIO > I2 pH 5–8

Bacteria (spores) I2 > HIO pH 5–7

Viruses HIO > I2 pH 8–9
Protozoaa I2 > HIO pH 5–7
Information about suitable pH is based on abundance of the most effective iodine species for a certain microbial group. Overall,
vegetative bacteria are most susceptible.
a
elemental iodine is effective against Giardia cysts but not effective against Cryptosporidium oocysts.

While these tendencies hold true for microorganisms suspended in clean water, disinfection efficacies can
be altered in the presence of turbidity and in poor quality water. The underlying reason is that although
hypoiodous acid is more reactive and has a higher oxidation potential, it has less penetrating power than
elemental iodine. If microorganisms are sheltered in particles, as found in turbid and poor quality water,
the enhanced penetrating power becomes more important than overall reactivity (Ellis et al., 1993). Even
if microorganisms are not attached to particles, the higher oxidation potential of hypoiodous acid
(prevalent at pH 8–9) might lead to preferential reaction with oxidizable organic matter (e.g. in the case of
turbid water with elevated total organic content) leaving less residual available for disinfection (Ellis et
al., 1993). More information on the effects of turbidity can be found in Section 2.2.2. Karalekas et al.

5
 Iodine as a drinking-water disinfectant

(1970) reported the effect of 1 ppm iodine on 6 different bacterial species. A noticeable reduction of the
germicidal effect was reported when increasing the pH from 5 to 9 (while noticing little difference
between pH 5 and 7). A slight decline in disinfection efficacy against E. coli and faecal streptococci was
also observed by Ellis & van Vree (1989) when increasing the pH from pH 7 to 8.5. The reduced efficacy
of iodine at higher pH was explained by Ellis et al. (1993) by the progressive decline of free iodine
residual. In studies on the effects of water quality and pH on inactivation of hepatitis A virus (HAV),
poliovirus 1 and echovirus 1 by 8 and 16 mg/L doses of iodine, HAV was inactivated more efficiently by
iodine than were the other two test viruses, and the order of virus inactivation was:

HAV > echovirus 1 > poliovirus 1 (Sobsey et al, 1991).

Virus inactivation was generally more effective at higher pH, in cleaner water, at higher temperature and
at higher iodine dose.

The partitioning into different chemical species with different disinfection power is not only dependent on
pH, but also the initial concentration of titratable iodine (Chang, 1966). The lower the iodine
concentration, the higher the relative percentage of hypoiodous acid at a given pH.

2.1.2.2 Effect of temperature

For iodine, the pH effect on disinfection efficacy is more noticeable at lower temperatures (Ellis et al.,
1993). In general, higher doses of iodine are required at lower temperatures to achieve the same degree of
disinfection (Chambers et al., 1952). As with chlorine, the reason can be found in the lower reactivity of
the disinfectant at lower temperature as the reaction rate is negatively correlated with the temperature via
the reaction constant. At low temperatures near the freezing point, a higher contact time is therefore
required to compensate for the loss in reactivity. Chang & Morris (1953) reported a doubling of required
contact time when decreasing the temperature from 25 oC to near freezing temperature (2–3 oC).
Temperature dependence of disinfection efficacy is however not fully understood as different effects
might counter-act each other. Ellis et al. (1993) found better germicidal performance at 5 oC than at 20 oC,
whereas an increase to 35 oC further reduced the effectiveness. This contradicts previous findings but was
explained by an increase in the oxidation potential at higher temperatures leading to faster inactivation
and less residual. The authors concluded that higher temperatures favour increased hydrolysis leading to
higher concentrations of hypoiodous acid which, in turn, has a higher oxidation potential than elemental
iodine.

2.2 Efficacy of iodine

2.2.1 Bactericidal efficacy of iodine
Chang & Morris (1953) investigated the bactericidal effects of a number of Ct combinations of iodine on
different bacterial pathogens. Tests conducted with E. coli showed that iodine concentrations of ≥ 0.05
ppm consistently reduced the culturability of 104 bacteria cells/mL to less than 1 cell/mL within 10 min
(25 oC, pH 8.1–8.5). Other results obtained when exposing 106 E. coli cells/mL to different iodine
concentrations are shown in Table 4 below.

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 Iodine as a drinking-water disinfectant

Table 4: Bactericidal efficacy of iodine (adapted from Chang & Morris, 1953)

Iodine concentration (in ppm) Viable cells/100 mL (log10 reduction)

Initial 30 min 5 min 10 min 20 min 30 min

1.0 0 1600 (2.80) 540 (3.27) 240 (3.62) 130 (3.89)

2.0 1.2 4.6 (5.34) 1.0 (6.00) 1.0 (6.00) 2.2 (5.66)
3.0 1.6 4.6 (5.34) 4.6 (5.34) 4.6 (5.34) < 1 (6.00)
4.0 2.6 24 (4.62) 6.9 (5.16) 2.5 (5.60) 1.0 (6.00)
5.0 3.3 < 1 (6.00) < 1 (6.00) < 1 (6.00) < 1 (6.00)

Bactericidal efficacy of different iodine concentrations to reduce viability of E. coli spiked into tap water at an initial
concentration of 106 cells/mL. A standard iodine dose of between 7 to 9 ppm was used to meet the iodine demand in the tap water
and to obtain a bactericidal residual of 1 to 5 ppm. The experiment was performed at 25 oC and a pH between pH 8.1 to 8.5.
Adapted with permission from: Chang S, Morris J (1953). Elemental iodine as a disinfectant for drinking water. Ind Eng Chem.
45: 1009–12. Copyright (1953) American Chemical Society.

Chang & Morris (1953) reported stronger inactivation than seen with E. coli for other enteric bacteria
including, Salmonella typhimurium, Shigella dysenteriae and Vibrio cholera, with initial iodine
concentrations of 7–8 ppm and pH 4.5–8.1. The authors reported that there was no effect of pH on
bactericidal efficacy of iodine in the range pH 4.5–8.1. Similar (but declining) results were obtained with
values up to pH 10, which is in sharp contrast to the strong pH dependence of chlorine.

2.2.2 Disinfection in the presence of turbidity

There is limited information discussing the effects of turbidity on the disinfection capability of iodine.
When testing the effect of ammonium and urea on the efficacy of iodine disinfection, concentrations up to
5 ppm were not found to have any measurable effect on the inactivation of E. coli (Chang & Morris,
1953). The same held true when adding different clays in concentrations of up to 500 ppm. It is generally
accepted that iodine shows less reactivity with organic nitrogenous impurities compared to chlorine
(Punyani et al., 2006) but does react to produce iodamines. The organic colour of water (due to the
presence of natural organic substances) is associated with iodine demand and reduced efficacy. At organic
colour concentrations > 70 ppm, a doubling of the dose was found to be required for disinfection. A study
by Ellis & van Vree (1989) found that when supplementing water with sediments from a natural stream,
the stepwise increase in turbidity up to a maximum of 1000 nephelometric turbidity units (NTU) reduced
the germicidal effectiveness of iodine.

In general, the disinfection capability of iodine, as with all disinfectants is reduced with increasing
turbidity as microorganisms can be protected from the iodine by adsorption to, or enmeshment in, solid
particles in water. In addition, there may be an increasing disinfectant demand due to reactions between
organic particles and the disinfectant. Sobsey et al. (1991) reported that the inactivation of HAV by iodine
at doses of 8 and 16 mg/L was less effective in “dirty water” (i.e. 10 mg/L of a 1:1 mixture of humic and
fulvic acids and 5 NTU of bentonite clay turbidity). Ellis et al. (1993) applied iodine to water
supplemented with stream sediments to achieve three different turbidity ranges (5–7, 50–54 and 93–97

7
 Iodine as a drinking-water disinfectant

NTU). Water was additionally adjusted to values of pH 6, 7.5, and 9 and different temperatures (5, 20,
and 35 oC). Under all conditions tested, a dose of 3 mg/L iodine with a contact time of 30 min was found
sufficient to inactivate E. coli. When supplementing water with digested sludge (up to the highest
turbidity range) or raw sludge (5–7 NTU), doses of 8 or 10 mg/L iodine were necessary to achieve
inactivation for the same contact time. The authors argued that the nature of the turbidity was more
important than its density. It was hypothesized that the higher organic and nitrogen content of the sludge
compared to the stream sediments was responsible. When comparing disinfection efficacy with chlorine
at 1.0 mg/L, chlorine was reported to be slightly more effective for water containing stream sediments
(e.g. at 20 ˚C and pH 7.5 the percentage inactivation of E. coli ranged from 99.52–100% for chlorine at
turbidities between 94–5 NTU, with the corresponding values for iodine ranging between 98.58–99.97%).
However, iodine was found more efficient in cases where sludge was added, particularly at the higher
temperature and pH values (e.g. at 20 ˚C and pH 7.5, percentage inactivation of E. coli ranged from 21.7–
38.74% for chlorine at turbidities between 97–5 NTU, with the corresponding values for iodine ranging
between 42.40–50.70% [Ellis et al., 1993]).

2.2.3 Iodine-based disinfection products

Iodine-based disinfection products available today can be divided into two categories; iodine solutions
and iodine resins. A summary of the disinfection capabilities of each is given in Table 5.

2.2.3.1 Iodine solutions

Iodine solutions are made by adding iodine (e.g. tincture of iodine, a 2% iodine solution), or by adding a
tablet containing iodine, a carrier, and stabilizing agents to enhance dissolvability (e.g. tetraglycine
hydroperiodide, sodium acid pyrophosphate and talc) to the water to be disinfected. The United States
Army has utilised iodine as a drinking-water disinfectant since 1952, issuing iodine-based tablets to
American soldiers. The United States Army continues to provide iodine-based tablets in addition to other
emergency field drinking-water products. Today, there are several commercial off the shelf individual
water purification devices that use iodine for disinfection.

For non-drinking-water disinfectant applications, iodine has been compared with chlorine and bromine as
alternative disinfectants for swimming pools. Although not directly related to the use of iodine as a
drinking-water disinfectant, these studies provide useful evidence of the efficacy of iodine for water
disinfection and the tolerance of individuals to residual concentrations of iodine. Typical of the now dated
studies, Black et al. (1959) investigated the effectiveness of iodine solutions for disinfecting public and
domestic swimming pools in Florida, USA. The solutions were added in the form of potassium iodide
over three weeks (twice weekly) at a dose equivalent to 1–2 ppm of iodine. The crystalline potassium
iodide was either spread over the surface of the pool together with a small amount of chlorine to release
free iodine, or uniformly distributed through a recirculation system. Iodine was found to be fully effective
in meeting bacteriological standards. The amount of iodine required for public pools with high bathing
activity was reported to be only slightly higher than required for pools with low bathing load (domestic
pools), suggesting that the iodine residual appeared to be less sensitive to bathing load than the chlorine
residual. The authors considered that this was due to iodine not reacting with ammonium, as does
chlorine. However, the reason is more likely to be due to the direction of the equilibrium between iodine
and ammonium. The study concluded that a daily dosage of 1 or 2 ppm of iodine would suffice to
disinfect domestic or public pools. This translates into a residual concentration of approximately 0.2 ppm
(Black et al., 1959).

8
 Iodine as a drinking-water disinfectant

Available evidence indicates that iodine solutions can be effective disinfectants against bacteria and, to a
lesser extent, viruses. Recommended dosages range from between 4 and 16 mg/L with contact times
ranging from 20–35 min, resulting in Ct values of 80–560 mg·min/L to achieve a 6 log10
reduction/inactivation of bacteria and a 4 log10 reduction/inactivation of viruses. Iodine is least effective
against protozoa and in particular, ineffective against Cryptosporidium parvum oocysts, where the doses
and contact times required are impractical for drinking-water disinfection (Gerba et al., 1997).

2.2.3.2 Resins
Iodine resins are solid-phase iodine disinfectants through which water is passed, with disinfection
occurring through direct contact of the microorganisms and the iodine sorbed onto the resin as
exchangeable ions. Iodine resins are generally considered demand-release disinfectants as iodine is
released to the microorganism after coming into contact with the resin, and generally produce a dilute
iodine residual. As is the case with iodine solutions, available data on iodine resins indicates they are
effective disinfectants against bacteria, viruses, and some protozoa (Punyani et al., 2006; Vasudevan &
Tandon, 2010). However, the resins have not, to date, been proven effective against Cryptosporidium
oocysts.

Resin-based iodine release systems comprise (1) organic iodide compounds, (2) iodophors (iodine in
combination with non-ionic surfactants) and (3) iodine incorporated resins (Punyani et al., 2006). Iodine
resins used in individual water purification devices are generally combined with other treatment
processes, such as filtration, to remove iodine residuals and iodine-resistant microorganisms. Modern
applications of resins have resulted in an increase in their use. Devices used by National Aeronautics and
Space Administration for space flights are prominent examples. Controlled release of iodine on board the
International Space Station Alpha is achieved through a flow-through device (referred to as Microbial
Check Valve) containing an iodinated polymer (Atwater et al., 1996; Gibbons et al., 1990). The iodine
residual concentration released into the water stream flow is a maximum of approximately 2 mg/L. The
released dissolved iodine undergoes a series of hydrolytic reactions resulting in the formation of iodide,
triiodide, hypoiodous acid and hypoiodide, with different biocidal capabilities associated to each
inorganic species (Punyani et al., 2006; Venkobachar & Jain, 1983). Another resin employed by National
Aeronautics and Space Administration consists of the iodine-polyvinyl pyrrolidone (iodine-PVP)
complex which releases iodine and iodide at concentrations of 2–3 mg/L and 1.5 mg/L, respectively
(Punyani et al., 2006). Again, the dissolved iodine speciates into a variety of different inorganic
compounds. Greatest biocidal activity can be attributed to iodine and hypoiodous acid (Gazda et al., 2004;
Gottardi, 1991).

A number of other resins have been developed with some promising results. Considering the potential
health impact of released aqueous iodine, Punyani et al. (2006) proposed the development of resins that
do not release iodine, but inactivate microorganisms during flow through by contact. Whereas resins
loaded with iodate did not exhibit a germicidal effect, polyiodide resins were reported to be efficient for
drinking-water disinfection (Vasudevan & Tandon, 2010).

9
 Iodine as a drinking-water disinfectant

Table 5: Disinfection capabilities of iodine solutions and resinsa

Parameter Iodine solutions Iodine resins

General Cysts most resistant. Achieving Giardia Cysts most resistant. Achieving Giardia cyst
cyst inactivation will ensure adequate inactivation will ensure adequate bacteria and
bacteria and virus inactivation. virus inactivation.

Bacteria 4 log10 reduction at Ct values < 10 Triiodide and pentaiodide resins can potentially
mg·min/L.b provide a 6 log10 reduction under most natural
water quality conditions.

Viruses 2 log10 reduction at Ct values of 15–75 Triiodide and pentaiodide resins can potentially
mg·min/L.c provide a 4 log10 virus reduction under most
natural water quality conditions.
4 log10 reduction for HAV, poliovirus 1
and echovirus 1 by doses of 8 and 6
mg/L in 60 min or less, depending on
water quality, pH and temperature.
Giardia cysts 3 log10 reduction at Ct values of 45–241 3 log10 reduction at 25 oC and 4oC using
mg·min/L at > 20 oC. Provide additional pentaiodide resin compared with 0.2–0.4 log
contact time and higher Ct values at < 20 reduction with triiodide resin. Additional contact
o
C to achieve 3 log inactivation. time after passing through resin needed compared
to iodine solutions.

Cryptosporidium Not effective at practical Ct values.d Not effective at practical Ct values.d

oocysts
Effect of Major effect. Increase contact time Major effect.e Increase contact time after passing
temperature and/or dose at colder temperatures. Ct through pentaiodide resin at colder temperatures.
values up to 720 mg·min/L Allow up to 40 min additional contact time for
recommended for Giardia cyst Giardia cysts inactivation in colder waters (< 5
inactivation in colder waters (< 5 oC). o
C).
Effect of pH Minor effect. Generally effective over Minor effect. Generally effective over pH range
typical pH levels for natural waters. typical for natural waters.
Effect of Affects disinfection capability. Provide Affects disinfection capability. Heavy organic
Turbidity additional contact time and/or increase matter loading can significantly reduce
iodine dose in more turbid waters. disinfection capability.
Source: Adapted from Technical Information Paper #-31-005-0211 (2011).
a
Testing was carried out using iodinated resins only, with no filter applied, as would normally be found in individual water purification devices.
Whilst bacteria and viruses are not physically filtered by the resin, due to electrostatic interactions, Giardia cysts and Cryptosporidium oocysts
are filtered by the resin bed. However, subsequent use of the resin leads to release or flushing of cysts and oocysts, which could remain viable.
b
Assuming a contact time of 20 min, a 0.5 mg/L iodine residual would be necessary to provide 4 log10 reduction of E. coli at near neutral pH at
any temperature encountered in natural waters (20 min x 0.5 mg/L = 10 mg·min/L).
c
2 log10 reduction at near neutral to alkaline pH levels (pH 6–10) and various water temperatures (5–30 °C) at Ct values of 15–75 mg·min/L with
the higher Ct values occurring at lower pH levels and colder water temperatures.
d
Gerba et al. (1997).
e
Temperature dependence of disinfection efficacy is not fully understood as different effects might counter-act each other. Current “best-
practice” is given.

10
 Iodine as a drinking-water disinfectant

The residual iodine concentration with iodine resins is much less than concentrations from the
recommended doses of tablet or liquid forms of iodine (Table 6).

Table 6: Residual iodine in demand-free water using recommended doses of available product

Iodine products Recommended dose Residual concentration

per litre of watera of iodine

Iodine tablets (tetraglycine hydroperiodide) 1–2 tablets 8–16 mg/L

Iodine solution (tincture; 2%) 0.25–0.5 mL 4–8 mg/L

Providone-iodine solution (10%) 0.35–0.70 mL 4–8 mg/L

Saturated iodine crystals in water 13–26 mL 4–8 mg/L

Pentaiodide resin (room temp) - 1–2 ppmb

Triiodide resin (room temp) - 0.2 ppm

Triiodide resin at 42 oC - 1 ppm

Triiodide resin at 71 oC - 6–10 ppm

Triiodide resin and granular activated carbon - 0.01 ppm

Modified from Backer & Hollowell (2000).

a
Lower dose in clear, warm water (> 15 oC), higher dose in very cold or cloudy water. Disinfection activity is a function of
iodine, contact time and water temperature.
b
mg/L equivalent to ppm.

2.2.4 Comparison of efficacy with chlorine

The properties of iodine and chlorine differ in several important ways. Although speciation of iodine is
pH dependent, a notable property of iodine is that it provides protection across a wider pH range than
chlorine (Black et al., 1965; Ellis et al., 1993). Compared with chlorine, iodine has also greater chemical
stability and shows less reactivity with organic nitrogenous contaminants, leaving a higher free residual;
the reduced reactivity with organic contaminants leads to a reduction in iodine demand (Backer &
Hollowell, 2000). On the negative side, less is known about iodine in regard to disinfection performance
on some important pathogens in waters of different quality and above all on potential negative health
impacts. In addition, the lower reactivity of iodine compared to chlorine requires the use of higher doses.
A comparison with chlorine is given below:

Commonalities with chlorine:

 Different classes of microorganisms have different susceptibilities (e.g. neither are effective
against Cryptosporidium oocysts); and
 Effectiveness is impacted by temperature, concentration, contact time, pH and organic content.

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 Iodine as a drinking-water disinfectant

Advantages of iodine over chlorine:

 Provides protection across a wider pH range;
 Greater chemical stability;
 Less disinfection demand through reduced reactivity with organic nitrogenous impurities;
 Germicidal action of iodine occurs over a wider range of water quality conditions than chlorine;
and
 Works better for water of poor quality.

Disadvantages of iodine compared to chlorine (these relate mainly to potential health concerns, as
discussed fully in Section 3):
 The safety of long-term consumption of iodine when used as a drinking-water disinfectant is not
established;
 Excess iodine intake is not safe for people with thyroid disease; and
 Higher concentrations are required as compared to chlorine to achieve comparable disinfection
efficacy.

2.2.5 World Health Organization International Scheme to Evaluate Household Water

Treatment Technologies
Existing evidence pertaining to the effectiveness of disinfectants against all three classes of pathogens
which cause diarrhoeal disease, may not reflect actual use conditions in the field (e.g. water of varying
quality, shorter contact times). In order to comprehensively assess effectiveness, WHO has set tiered
health-based log10 reduction performance targets for household water treatment (HWT) products for the
removal and/or inactivation of bacteria, viruses and protozoa (WHO, 2011). These performance targets
are based on microbial risk models using assumed levels of reference pathogens in untreated water. Since
2014, WHO has been evaluating products against those performance targets through the WHO
International Scheme to Evaluate Household Water Treatment Technologies.3 Box 1 gives further
information on the Scheme. At the time of this report, iodine has not been tested but may be included in
future rounds.

3
http://www.who.int/water_sanitation_health/water-quality/household/scheme-household-water-treatment/en/

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 Iodine as a drinking-water disinfectant

Box 1 WHO International Scheme to Evaluate Household Water Treatment Technologies

The objective of the Scheme is to independently and consistently evaluate the microbiological
performance of household and POU water treatment technologies. The evaluation considers both
turbid and non-turbid water, and is carried out to manufacturers’ instructions for daily household
use.3 The results of the evaluation are intended to assist and inform Member States and procuring
UN agencies in the selection of these technologies.

The performance targets define treatment requirements in relation to source water quality for each
pathogen class as detailed below.

Performance Bacteria Viruses Protozoa Classification

target (log10 reduction (log10 reduction (log10 reduction (assuming correct and
required) required) required) consistent use)
 ≥4 ≥5 ≥4 Comprehensive
protection (very high
pathogen removal)
 ≥2 ≥3 ≥2 Comprehensive
protection (high
pathogen removal)
 Meets at least 2-star () criteria for two classes of Targeted protection
pathogens
‒ Fails to meet WHO performance criteria Little or no protection

The performance of HWT products is classified as 3-star (); 2-star (); and 1-star (),
denoting descending order of performance, based on log10 reductions of bacteria, viruses and
protozoa from drinking-water. Performance that does not meet the minimum target is given no
stars. Products that meet 3-star () or 2-star () performance targets are classified as
providing “Comprehensive protection” against the three main classes of pathogens which cause
diarrhoeal disease in humans. The use of these products is encouraged where there is no
information on the specific pathogens in drinking-water (and a prudent approach is to protect
against all three classes), or where piped supplies exist but are not safely managed. Products that
meet the performance targets for at least 2-star () for only two of the three classes of pathogen
are given one star () and are classified as providing “Targeted protection”. In general, the use of
these products may be appropriate in situations where the burden of diarrhoeal disease is high due
to known classes of pathogens, such as a cholera outbreak.

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 Iodine as a drinking-water disinfectant

3. Safety and toxicity of iodine

The health effects of iodine have been reviewed by a number of international bodies:

 European Food Safety Authority (EFSA, 2014);

 Council for Responsible Nutrition (CRN, 2013);
 USEPA, 2006;
 Agency for Toxic Substances and Disease Registry (ATSDR, 2004);
 World Health Organisation /Food and Agriculture Organisation (WHO/FAO, 2004);
 World Health Organisation (WHO, 2003);
 Expert Group on Vitamins and Minerals (EVM, 2003);
 European Commission Scientific Committee on Food (EC, 2002);
 Institute of Medicine (IOM, 2001); and
 Joint FAO/WHO Expert Committee on Food Additives (JECFA, 1988).

In this section, opinions from expert bodies on intake of iodine, as detailed above, are described. In
addition, a detailed assessment of recent4 toxicological literature for iodine was undertaken and the
relevant findings are included here.

3.1 Human exposure

Iodine is an essential dietary element for mammals. It is required for the synthesis and function of the
thyroid hormones thyroxin (T4) and triiodothyronine (T3), as well as being the precursor of
iodotyrosines. Through these hormones, iodine has an important role in energy-yielding metabolism and
on the expression of genes that impact many physiological functions, from embryogenesis to growth and
development, neurological and cognitive functions (EFSA, 2014).

The only natural sources of iodine for humans and animals are the iodides in food and water. The use of
iodine and iodophors for sanitizing purposes has been reported to result in significant amounts of iodine
entering the food chain (Phillips, 1997). The iodine content of foods is highly variable both between food
categories as well as within each category. Marine products such as shellfish and molluscs, and eggs and
milk are the richest sources of dietary iodine (Phillips, 1997). In Japan, iodine intake exceeds that of most
other countries, primarily due to substantial seaweed consumption. Zava & Zava (2011) utilized
information from a number of sources including dietary records, food surveys, urine iodine analysis (both
spot and 24-hour samples) and seaweed iodine content, to estimate daily Japanese iodine intake. The
authors estimated that the Japanese iodine intake averages 1000–3000 μg/day (1–3 mg/day). The iodine
content of drinking-water is also highly variable. In Denmark, tap water concentrations of iodine from a
number of locations were reported to contain between < 1.0–139 µg/L (median 2.6 µg/L) (Pedersen et al.,
1993). Drinking-water in the USA has a reported mean concentration of total iodine of 4 µg/L, with a
maximum concentration of 18 µg/L (Andersen et al., 2008). Chronic excessive iodine intake has been
linked to development of goitre (enlarged thyroid gland) (Zhao et al., 2000), early onset of sub-clinical
thyroid disorders, hyperthyroidism (excessive production and/or secretion of thyroid hormones) and
hypothyroidism (diminished production of thyroid hormones), an increased incidence of autoimmune

4
To November 2013, with further ad hoc searches were carried out up to the closing date for public review (16 December 2016).

14
 Iodine as a drinking-water disinfectant

thyroiditis (inflammation of the thyroid gland) and increased risk of thyroid cancer (Laurberg et al., 1998;
Teng et al., 2006).

In contrast, iodine deficiency remains a major public health concern in many countries, including some
European countries (WHO/UNICEF/ICCIDD, 2007; Zimmermann & Andersson, 2011; Andersson et al.,
2012). Chronic deficiency has been linked with compensatory thyroid hyperplasia with goitre, with an
associated increase in risk of thyroid cancer. In an attempt to counteract the deficiency, iodine
fortification of salt is recommended by WHO and has been implemented in approximately 120 countries
worldwide (WHO/UNICEF/ICCIDD, 2007). Of these, 40 are European countries: 5 it is mandatory in 13
countries, voluntary in 16 and not regulated in the remaining countries. The amount of iodine added
varies from 10–75 mg/kg salt with a majority of values in the range 15–30 mg/kg.

3.2 Guideline values

3.2.1. WHO Guidelines for Drinking-water Quality
The WHO Guidelines for Drinking-water Quality (WHO, 2017) did not formally establish a guideline
value for iodine. Iodine was last reviewed by WHO for the Guidelines for Drinking-water Quality in
1993, when it was concluded that available data suggested that derivation of a guideline value for iodine
on the basis of information on the effects of iodide was inappropriate and there were few relevant data on
the effects of iodine. Also, because iodine is not recommended for long-term disinfection, lifetime
exposure to iodine concentrations such as might occur from drinking-water disinfection is unlikely
(WHO, 2003).

3.2.2 Other values

In 1988, the Joint FAO/WHO Expert Committee on Food Additives (JECFA, 1988) set a Provisional
Maximum Tolerable Daily Intake for iodine of 1 mg/day (17 μg/kg body weight [bw] per day) from all
sources. This upper limit was reaffirmed by WHO in 1994 (WHO, 1994). This was based on the tolerance
of high doses of iodine in healthy iodine-replete adults and did not include neonates and young infants. In
light of the recognition that excess iodine could lead to hypothyroidism, hyperthyroidism and thyroid
autoimmunity in vulnerable individuals, in 2004 the WHO/FAO recommended the following nutrient
intakes for iodine (WHO/FAO, 2004):

 Infants and children 0–59 months: 90 µg/day

 Children 6–12 years: 120 µg/day
 Adolescents and adults, from 13 years of age through adulthood: 150 µg/day
 Pregnant women: 200 µg/day
 Lactating women: 200 µg/day

In 2001, the Food and Nutrition Board at the United States National Institute of Medicine recommended
the following dietary intakes for iodine (IOM, 2001):

 Infants
o 0–6 months: 110 µg/day

5
List of countries available from: http://www.who.int/nutrition/publications/VMNIS_Iodine_deficiency_in_Europe.pdf

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 Iodine as a drinking-water disinfectant

o 7–12 months: 130 µg/day

 Children
o 1–3 years: 90 µg/day
o 4–8 years: 90 µg/day
o 9–13 years: 120 µg/day
 Adolescents and Adults
o Males age 14 and older: 150 µg/day
o Females age 14 and older: 150 µg/day

 Pregnant women: 220 µg/day

 Lactating women: 290 µg/day

The same group derived tolerable upper intake levels of between 200 and 1100 µg/day (children between
1–3 years and all adults respectively) from all sources. Recommendations for adults were based on
changes in serum thyrotropin concentrations in response to varying levels of ingested iodine in adults,
with children’s levels obtained by extrapolation from adult levels with adjustment on the basis on body
weight (IOM, 2001).

In 2002, the European Commission Scientific Committee on Food (EC, 2002) provided a Tolerable
Upper Intake Limit (UL) for iodine of 600 µg/day for adults (including pregnant and lactating women).
This value was based on dose-response studies of short duration (two weeks) in small numbers of subjects
(n=10–32). An increased response of thyroid stimulating hormone (TSH) to thyrotropin-releasing
hormone (TRH) at intakes of 1700–1800 μg/day was reported by Gardner et al. (1988) and Paul et al.
(1988) but changes were not associated with any adverse clinical outcome. In a five-year study, Stockton
& Thomas (1978) also reported an absence of clinical thyroid pathology following similar intakes. An
uncertainty factor of 3 was applied to the highest intake assessed in these studies (1800 µg/day) to derive
the UL for adults. For children, an adjustment based on body weight was applied to the adult value. The
report concluded that dietary intakes are unlikely to exceed 500 μg/day, since the 97.5 percentile intake in
European men is 434 μg/day.

The UK’s Expert Group on Vitamins and Minerals (EVM, 2003) set a guidance level for iodine intake,
concluding that neither human nor animal data were sufficient to set a UL value. Following assessment of
the findings from several clinical studies of supplemental iodine, the author’s concluded that 500 μg/day
of supplemental iodine “would not be expected to have any significant adverse effects in adults.” This led
to recommendation of guidance levels of 500 μg/day for supplemental iodine and 930 μg/day for total
intake from all sources (EVM, 2003).

The Council for Responsible Nutrition (CRN, 2013) recommended an upper limit for iodine intake of 500
µg/day based on the absence of adverse effects in healthy adults following daily oral intake of iodine
supplements of 500 µg. In 2014, the European Food Safety Authority published Adequate Intake (AI)
levels for iodine in different age groups (including pregnant and breast-feeding women), based in part on
a large epidemiological study in European school-aged children (EFSA, 2014). The study showed that
goitre prevalence is lowest for a urinary iodine concentration <100 μg/L, associated with iodine intakes of
150 µg/day in adults.

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 Iodine as a drinking-water disinfectant

From this, the following AI levels were recommended:

 Infants (< 1 year of age): 70 μg/day

 Children
o Aged between 1–3, 4–6 and 7–10 years: 90 μg/day
o Aged between 11–14 years: 120 μg/day
o Aged between 15–17 years: 130 μg/day
 Adults: 150 μg/day
 Pregnant or breast-feeding women: 200 μg/day

For individuals from countries with long-standing iodine deficiency disorder, the Expert Committee on
Human Nutrition of the Agence Française de Sécurité Sanitaire des Aliments has suggested a provisional
maximal tolerable daily intake of 500 μg/day to avoid the occurrence of hyperthyroidism (AFSSA, 2001).

3.3 Human toxicity data

3.3.1 Toxicokinetics

3.3.1.1 Absorption
Iodine is readily absorbed through inhalation and ingestion, with dermal absorption being extremely low
(< 1% of applied dose). Human volunteers exposed to radioactive elemental iodine vapour by inhalation
showed clearance with a half-life of 10 minutes, with the majority of iodine being removed by
mucociliary clearance to the gastrointestinal (GI) tract (Black & Hounam, 1968; Morgan et al., 1968).
Iodine ingested in the form of water-soluble salts shows 100% absorption from the GI tract (Fischer et al.,
1965). Absorption of iodine from the GI tract has been shown to be similar in adults, adolescents,
children and older infants, however, uptake in newborns is reported to be between 2–20% lower (Ogborn
et al., 1960; Morrison et al., 1963).

Iodine ingested in forms other than iodide is reduced to iodide in the gut prior to absorption by the small
intestine (Fisher et al., 1965; Fish et al., 1987; Hays, 2001) with an efficacy of 92% (IOM, 2001; Jahreis
et al., 2001; Aquaron et al., 2002). Iodide absorption is reduced in the presence of humic acids in
drinking-water (Gaitan, 1990), and of thiocyanates, isothiocyanates, nitrates, fluorides, calcium,
magnesium and iron in food and water (Ubom, 1991).

3.3.1.2 Distribution
In human volunteers exposed to radiolabelled iodine via ingestion, between 20–30% of the dose was
distributed to the thyroid within 10 hours, with between 30–60% being excreted in urine (Morgan et al.,
1967a, b). Of total body iodine typically 70–90% is concentrated in the thyroid gland. Maternal exposure
to iodine results in exposure of the fetus to thyroid hormones, with accumulation of iodine in the fetal
thyroid gland commencing at around 70–80 days gestation (Evans et al., 1967; Book & Goldman, 1975).

3.3.1.3 Metabolism
As noted above, iodine undergoes rapid conversion to iodide which is then transported by the sodium
iodide symporter to the thyroid and utilised for the production of T4 and T3 hormones (Morgan et al.,

17
 Iodine as a drinking-water disinfectant

1967a, b; Black & Hounam, 1968). Competition with sodium iodide symporter transport of iodine occurs
from exposure to numerous anions including perchlorate, chlorate, nitrate and thiocyanate.

3.3.1.4 Elimination
Around 97% of iodine is excreted in the urine as iodide, with faecal elimination of between 1–2% (Larsen
et al., 1998; Hays, 2001). Absorbed iodine can also be excreted in breast milk, saliva, sweat, tears and
exhaled air (Cavalieri, 1997). The elimination half-life of absorbed iodine is considerably variable
between individuals, and has been estimated as 31 days for healthy adult males (Van Dilla & Fulwyler,
1963; Hays, 2001).

3.3.2 Acute toxicity

Several biological mechanisms protect against acute iodine toxicity; these include reduced iodine uptake
and preferential production of the more heavily iodinated thyroid hormones. Not all exposed subjects will
react to excess iodine. Clinical features of acute iodine toxicity that have been produced following
accidental or deliberate ingestion, or medical procedures such as wound irrigation, include GI disturbance
(vomiting and diarrhoea), metabolic acidosis, seizure, stupor, delirium and collapse. Sensitivity reactions,
such as iodide mumps, iododerma and iodide fever may also occur following treatment with iodine-
containing drugs, or the use of radiographic contrast media (EVM, 2003).

Deaths (usually within 48 hours) in humans have occurred for iodine ingested in tinctures at doses
ranging from 1200–9500 mg (17–120 mg/kg). Acute oral toxicity is primarily due to irritation of the GI
tract, marked fluid loss and shock occurring in severe cases (ATSDR, 2004).

3.3.3 Repeat dose toxicity

A large number of human experimental, clinical, and epidemiological studies on the effects of repeat
doses of excess iodine on human health has been reported.

3.3.3.1 Systemic effects

Both sub-acute (≤ 30 days) and sub-chronic (30–90 days) exposure studies for iodine intake have been
reported:

Men who drank iodized water providing iodine doses of 0.17–0.27 mg/kg bw per day for 26 weeks
reported no adverse effects (Morgan & Karpen, 1953).

The ingestion of about 3 mg iodine/day for 6 months during daily mouth-rinsing with an iodine-
containing mouthwash had no effect on thyroid function (Ader et al., 1988).

A study on the effects of doses of 250, 500 or 1500 μg iodide/day for 14 days on thyroid function was
carried out in 9 euthyroid men (normal thyroid function; mean age 34 years) and 23 euthyroid women
(mean age 32 years) with 5 age-matched controls (Paul et al., 1988). The parameters examined were
protein bound iodine (PBI) of the thyroid total serum iodine, T4, T3, TSH, integrated 1-hour serum TSH
response to an intravenous dose of 500 μg TRH, and 24-hour urinary iodine excretion. The dietary intake
of iodine was estimated from the urinary iodine excretion to be approximately 200 μg/person/day making
the total ingested doses approximately 450, 700 and 1700 µg iodide/day. The estimated dose of 1700

18
 Iodine as a drinking-water disinfectant

μg/day was associated with an increase in total serum iodine without affecting the PBI, a significant
decrease in serum T4 and T3 levels and an increase in TSH levels. Administered doses of 700 and 450
µg/day did not significantly affect the measured parameters. Only 1700 μg/day increased the TSH
response to TRH (in women more than in men). The TSH response to TRH was also increased, though
not significantly, in the individuals receiving 700 μg iodide/day. No biochemical effects were detected
with 450 μg of iodide/day. However, this study used only small groups, extended over only 2 weeks and
the dietary iodine intake was not determined analytically but was estimated.

In another study, 10 males (mean age 27 years) were treated for 2 weeks with either 500, 1500 or 4500 μg
iodide/day (Gardner et al., 1988). The dietary intake was estimated from urine iodine excretion to have
been approximately 300 μg/person/day making the total ingested doses approximately 800, 1800 or 4800
µg iodide/day. Serum levels of T4, T3, TSH, PBI, and total iodide, the TSH response to intravenous TRH
and 24-hour urinary excretion of iodide were measured before treatment and again on day 15. Serum T4
levels decreased significantly after ingestion of 1800 μg and 4800 μg/day but did not change with 800
μg/day. Serum T3 levels did not change following administration of any of the doses. Serum TSH levels
remained unchanged in those receiving 800 μg/day but increased in those receiving 1800 μg and 4800
μg/day. The TSH response to TRH was significantly enhanced with all iodide doses administered. No
adverse effects were reported and no significant symptoms of thyroid dysfunction were noted. Again,
only small groups of males were studied, exposure was rather short and the actual dietary intake of iodine
was not determined analytically but estimated.

Chow et al. (1991) assessed the effect of supplementing normal dietary intakes of iodide to give a total
iodide intake of approximately 750 μg iodide/day, or a placebo for a period of 28 days. Volunteers were
groups of women aged 25–54 years. They were either thyroid antibody positive (subclinical Hashimoto’s
thyroiditis) (n=20), antibody negative (n=30), aged 60–75 years and from an area with adequate dietary
iodine supply (n=29) or from an area that was previously iodine deficient (n=35). In all iodine-
supplemented groups, mild biochemical hypothyroidism was present, evidenced by decreases in T4 levels
and increases in TSH levels. None of the groups on supplemental iodide showed any incidence of
hyperthyroidism. Following iodide supplementation TSH levels increased above the normal level of 5
milli-international units (mU)/L in 3 of the 60–75 year-old subjects, while the raised TSH levels increased
even further in 2 antibody-positive subjects.

Chronic (> 6 months) exposure through ingestion of iodine at levels > 0.03 mg/kg bw is considered to be
associated with adverse health effects (ATSDR, 2004). The introduction of iodized bread in The
Netherlands raised the daily intake by 120–160 μg iodine resulting in an increase in the incidence of
hyperthyroidism (Van Leeuwen, 1954). The consumption of winter milk6 in the UK raised the iodine
intake of women to 236 μg/day and of men to 306 μg/day and was also associated with a peak incidence
of hyperthyroidism (Nelson & Phillips, 1985). In 32 young Swiss adults with simple goitre (and urinary
iodine excretion of 32 μg/day) administered 200 μg iodine/day, only one case of transient
hyperthyroidism appeared which showed a serum T4 of 14 μg/100 mL, a serum T3 of 293 ng/100 mL,
suppressed TSH, tachycardia and weight loss (Baltisberger et al., 1995).

6
Seasonal differences in the iodine content of milk are apparent and vary directly in relation to farming practices.

19
 Iodine as a drinking-water disinfectant

Peace Corps volunteers in Niger, West Africa using iodine-resin water purification devices for 32 months
during the period 1995–1998, showed an increased incidence (42%) of thyroid abnormality but effects
were reversed when iodinated water consumption ceased (Pearce et al., 2002). The purification devices
delivered a mean concentration of 10 mg iodine/L to the drinking-water, which with a daily consumption
amongst volunteers of 5–9 L resulted in consumption of 50 mg/iodine per day (300 times the
recommended dietary allowance for the USA at that time). The adjusted odds ratio for thyroid
dysfunction (abnormal thyrotropin) adjusted for age, sex, and other potential confounding factors, was 3.9
(95% CI 1.1–14.3) (p < 0.04) for the devices, with a positive relation with duration of exposure (adjusted
odds ratios 4.6 and 10.9 at 6 and 12 months, respectively).

In a 5-year study using iodinated drinking water (1 mg/L) supplied to 750 male and female prison in-
mates, no hyper- or hypothyroidism sensitization reactions and iodism (symptoms provided in the
following paragraph) were noted (Stockton and Thomas, 1978). The average dose was 30 μg/kg bw per
day. There was a statistically significant decrease in iodine uptake and an increase in PBI of the thyroid.
One hundred and seventy-seven women in-mates delivered 181 infants showing no thyroid-related
adverse effects. In four women who were already hyperthyroid, their symptoms became even more
severe. The difficulties with this study were the imprecise estimates of intakes from the diet and fluid
consumption of the participating individuals as well as the variable exposure time but the group size and
duration of exposure were adequate.

Although most individuals who ingest large amounts of iodine remain euthyroid (i.e. have normal thyroid
gland function) some will develop hypothyroidism with or without goitre or hyperthyroidism which can
manifest as thyrotoxicosis (inflammation of the gland), and changes in the incidence and types of thyroid
malignancies. Very large amounts of iodide may cause iodism, the symptoms of which resemble rhinitis
as well as salivary gland swelling, GI irritation, acneform dermatitis, metallic taste, gingivitis, increased
salivation, conjunctivitis and oedema of eye lids (ATSDR, 2004; Leung & Braverman, 2014). In children
aged between 5–15 years of age, 10 μg/kg bw per day is considered to be a no-observed-adverse-effect
level (NOAEL) based on thyroid effects (subclinical hypothyroidism with thyroid gland enlargement)
(Boyages et al., 1989; Chow et al., 1991).

It has been proposed that excess iodide intake may be a contributing factor in the development of
autoimmune thyroiditis in people who are vulnerable (Brown and Bagchi 1992; Foley 1992; Rose et al.,
1997; Safran et al., 1987); however, evidence to support this in humans is incomplete.

3.3.3.2 Neurotoxicity
Iodine-induced hypothyroidism in sensitive populations (including fetuses, newborn infants, and
individuals who have thyroiditis) has the potential to produce neurological effects (Boyages, 2000b). This
is particularly applicable to fetuses and newborn infants as thyroid hormones are essential to the
development of the neuromuscular system and brain. An iodine-induced hypothyroid state can result in
delayed or deficient brain and neuromuscular development of the newborn. Iodine-induced
hypothyroidism in an older child or adult would be expected to have little or no deleterious effects on the
neuromuscular system.

Iodine-induced hyperthyroidism presenting as thyrotoxicosis in sensitive individuals (including those

who are initially iodine deficient; those who have thyroid disease; including nodular goitre; Graves’

20
 Iodine as a drinking-water disinfectant

disease; those who have been previously treated with antithyroid drugs; and those who have developed
thyrotoxicosis from amiodarone or interferon-alpha treatments [Roti and Uberti, 2001]) may experience
neuromuscular disorders, including myopathy (muscular weakness), periodic paralysis, myasthenia gravis
(weakness in skeletal muscles), peripheral neuropathy, tremor, and chorea (involuntary movement
disorder) (Boyages, 2000a).

3.3.3.3 Reproductive and developmental toxicity

Chronic exposure to excess iodine has been shown to disrupt reproductive function secondary to thyroid
gland dysfunction. Induced changes in the menstrual cycle, including menorrhagia (excessive uterine
bleeding) and anovulation (no ovulation); spontaneous abortions, stillbirths, and premature births have
also been associated with hypothyroidism (Longcope, 2000a).

Reproductive impairments associated with hyperthyroidism include amenorrhea (no uterine bleeding),
alterations in gonadotropin release and sex hormone-binding globulin, and changes in the levels and
metabolism of steroid hormones in both females and males (Longcope, 2000b).

Exposure to iodine may give rise to developmental defects secondary to thyroid gland dysfunction
(Boyages, 2000a, b). As noted in Section 3.3.3.2, hypothyroidism may be associated with impairment in
neurological development of the fetus or growth retardation (Boyages, 2000a, b; Snyder, 2000a).

Hyperthyroidism has been associated with accelerated growth linked to accelerated pituitary growth
hormone turnover or a direct effect of thyroid hormone on bone maturation and growth (Snyder, 2000b).

3.3.3.4 Immunotoxicity
No data could be located regarding immunotoxic effects in humans following repeated exposure to
iodine.

3.3.3.5 Genotoxicity
No data could be located regarding genotoxic effects in humans following repeated exposure to iodine.

3.3.3.6 Carcinogenicity
The American Conference of Governmental Industrial Hygienists has classified iodine as A4 - not
classifiable as a human carcinogen (ATSDR, 2004). The International Agency for Research on Cancer
has not classified non-radioactive iodine (ATSDR, 2004).

The results from several epidemiology studies suggest that increased iodide intake may be a risk factor for
thyroid cancer in certain populations, in particular, those that are iodine-deficient (Bacher-Stier et al.,
1997; Harach & Williams, 1995; Franceschi, 1998; Franceschi & Dal Maso, 1999). Studies of
populations in which iodine intakes are sufficient have not found significant associations between iodine
intake and thyroid cancer (Horn-Ross et al., 2001; Kolonel et al., 1990).

A lowest-observed-no-effect level of 3.5 µg/kg bw per day has been identified based on thyroid cancer
prevalence in Salta, an endemic goitre area in Argentina (Harach & Williams, 1995; Bacher-Stier et al.,
1997).

21
 Iodine as a drinking-water disinfectant

3.4 Animal toxicity studies

Laboratory animals, poultry, pigs and cattle have a high tolerance to large iodine intakes. Animal data are
of limited value to humans because of species differences in basal metabolic rate and in iodine
metabolism (IOM, 2001).

3.4.1 Toxicokinetics
Rapid absorption of iodine vapour following inhalation exposure observed in humans is supported by
studies in rats, mice, dogs and sheep (Willard & Bair, 1961; Bair et al., 1963). Compounds of iodine were
also seen to be rapidly absorbed in monkeys when inhaled as vapours or aerosols, with a half-life of 10
min (Thieblemount et al., 1965; Perrault et al., 1967).

Absorption, distribution, metabolism and excretion data from animal studies for iodine exposure via the
GI tract, were not apparent from the reviews identified during the literature search.

3.4.2 Acute toxicity

Due to the rapid conversion of iodine to iodide in vivo, the acute toxicity of iodine has been poorly
studied. Conversely, the acute toxicity of iodides and iodates have been well studied and can be used to
estimate the acute toxicity of iodine.

The acute oral median lethal dose (LD50)7 for potassium iodide in rats was 3320 mg iodide /kg bw and in
mice, 1425 mg iodide /kg bw (Stokinger, 1981).

3.4.3 Repeat dose toxicity

3.4.3.1 Systemic toxicity

A number of experimental studies on the effects of chronic exposure to excess iodine or iodide,
particularly on thyroid function have been reported, with representative studies from different species
summarized below:

 Two strains of chickens (CS and OS), genetically vulnerable to autoimmune thyroiditis, were
given either 20 or 200 mg potassium iodide/L in their drinking water for the first 10 weeks of
their lives. At both levels the incidence of the disease was increased as shown histopathologically,
and also by measurements of, T4, T3 and thyroglobulin antibody titres (Bagchi et al., 1985).

 In female Wistar rats administered diets containing iodine concentrations between 0.015 and 0.23
mg/kg bw per day for 10 weeks, significantly enlarged thyroids were found at all doses, with a
dose-dependent increase at all doses (Fischer et al., 1989).

 Newton and Clawson (1974) reported a dose-dependent increase in thyroid weights of pigs
administered iodine at concentrations between 3 and 218 mg/kg bw per day.

 Female calves fed iodine at concentrations between 0.011 and 3.96 mg/kg feed twice daily for 5
weeks from day 4 of age showed a significant decrease in body weight gain at the highest dose;

7
The dose required to kill half the members of a test population after a specified test duration.

22
 Iodine as a drinking-water disinfectant

food intake was also decreased. Haematological changes (decreased packed cell volume) and
clinical signs of nasal discharge were noted in the highest dose group and lacrimation was noted
in the two highest dose groups (Jenkins & Hidiroglou, 1990).

 A NOAEL of 10 mg/L has been proposed for the most sensitive endpoint of thyroid hormone
imbalance in rats. This was based upon a decrease in T3 levels and an increase in T4/T3 ratio
after 100 days of iodine treatment (Sherer et al., 1991). When considering the use of rat models, it
should be noted that rats are much more sensitive to thyroid hormone imbalance than humans
(requiring around 10 times more T4/kg than humans).

3.4.3.2 Neurotoxicity
No data could be located regarding neurotoxic effects in animals following repeated exposure to iodine.

3.4.3.3 Reproductive and developmental toxicity

Arrington and colleagues (Arrington et al., 1965) investigated the reproductive and developmental
toxicity of iodine in a series of studies:

 Iodine administered to pregnant Long-Evans rats at a concentration of 2500 mg/kg in the diet for
12 days in the latter part of gestation was associated with an increased incidence of death in the
neonates, < 10% of the neonates survived for more than 3 days. Length of labour (parturition)
was also increased.

 Syrian hamster pups from mothers fed iodine at 2500 mg/kg in the diet for 12 days in the latter
part of gestation showed decreased feed intake (10%) and weaning weights at 21 days were
significantly less than controls.

 Pups from pregnant rabbits (Dutch and New Zealand) fed iodine at concentrations between 250
and 1000 mg/kg feed for 2–5 days before parturition showed decreased survival rates.

 Pregnant pigs receiving diets containing 1500 or 2500 mg iodine/kg feed for the 30 days prior to
parturition delivered litters that were unaffected by dietary levels of iodine that were toxic to
rabbits and rats.

In female rats administered 0, 500, 1000, 1500 and 2000 mg potassium iodide/kg diet throughout
gestation, lactation and weaning, pup survival was reduced from 93% in controls to 16% in rats given the
highest dose; milk secretion was also diminished. There were no adverse effects on ovulation rate,
implantation rate and fetal development (Ammermann et al., 1964). Brain enzymes of pups from pregnant
rats administered 11 mg potassium iodide/day in their drinking water (37 mg/kg bw per day) showed
transient increases in glutamate dehydrogenase and transient decreases in succinate dehydrogenase.
Phosphofructokinase and malate enzymes were increased; however, hexokinases were unaffected. Serum
T4 levels were also unchanged compared to controls (Morales de Villalobos et al., 1986).

In further studies a NOAEL of 10 mg/kg bw per day has been derived for reproductive and developmental
toxicity in rats administered iodine by oral gavage (based on no observed toxicity at any dose level). A

23
 Iodine as a drinking-water disinfectant

NOAEL for parental toxicity of 10 mg/kg bw per day was also established (based on no supported
changes at any dose level) (EC, 2002).

Mares given 48–432 mg iodine/day during pregnancy and lactation produced foals with disturbed
metabolism. The long bones of the legs of the foals showed osteopetrosis (hard, dense bones). Serum
phosphate and alkaline phosphatase levels were increased (Silva et al., 1987).

3.4.3.4 Immunotoxicity
No data could be located regarding immunotoxic effects in animals following repeated exposure to
iodine.

3.4.3.5 Genotoxicity (in vivo)

No data could be located regarding genotoxic effects in animals following repeated exposure to iodine.
(See 3.4.4 for in vitro genotoxicity studies.)

3.4.3.6 Carcinogenicity
Metaplasia of the thyroid was reported in rats given potassium iodide in their drinking water for two years
(dose not quoted by authors). This was thought to occur through a non-genotoxic proliferation dependent
mechanism (EVM, 2003)

3.4.4 In vitro toxicity studies

The mutagenicity data for iodine are generally negative; iodine has been shown to be non-mutagenic
using the mouse (TK +/-) lymphoma assay and no induction of unscheduled deoxyribonucleic acid
synthesis was seen in Syrian Hamster Embryo cells (ATSDR, 2004).

3.5 Vulnerable populations

Individuals identified as most vulnerable to iodine-induced toxicity in the form of hypothyroidism are
shown in Table 7.

24
 Iodine as a drinking-water disinfectant

Table 7: Risk groups for iodine-induced hypothyroidism (WHO/UNICEF/ICCIDD, 2007)

Risk group / subgroup

No underlying thyroid disease

Fetus and neonate, mostly preterm Secondary to transplacental passage of iodine or exposure of neonate to
topical or parenteral iodine-rich substances
Infant Occasionally reported in infants drinking iodine-rich water (China)
Adult In Japanese subjects with high iodine intake where Hashimoto thyroiditis
has been excluded
Elderly Reported in elderly subjects with and without possible defective
organification (incorporation of iodine into thyroglobulin to produce
thyroid hormone) and autoimmune thyroiditis
Chronic non-thyroid illness Cystic fibrosis
Chronic lung disease
Chronic dialysis treatment
Thalassaemia major
Anorexia nervosa
Underlying thyroid disease

Hashimoto thyroiditis
Euthyroid patients previously treated for Graves’ disease with 131I,
thyroidectomy, or antithyroid drugs
Subclinical hypothyroidism (particularly the elderly)
After transient postpartum thyroiditis
After subacute painful thyroiditis
After hemithyroidectomy for benign nodules
Euthyroid patients with a previous episode of amiodarone-induced
destructive thyrotoxicosis
Euthyroid patients with a previous episode of interferon-induced thyroid
disorders
Patients receiving lithium therapy

3.6 Toxicity of iodinated disinfection by-products

3.6.1 Formation and occurrence of iodinated disinfection by-products
When present in water, either at background levels or when used as a disinfectant, iodine has the ability to
form iodinated DBPs. These have been identified in some chloraminated drinking-water in countries
including the USA (Weinberg et al., 2002) and include:

25
 Iodine as a drinking-water disinfectant

 iodoacetic acid;
 bromoiodacetic acid;
 (Z)-3-bromo-3-iodopropenoic acid;
 (E)-3-bromo-3-iodopropenoic acid; and
 (E)-2-iodo-3-methylbutenedioic acid.

In addition, iodinated trihalomethanes (THMs) identified in chlorinated and chloraminated drinking water
(Richardson et al., 2007) have been identified as:

 dichloroiodomethane;
 bromochloroiodomethane;
 dibromoiodomethane;
 chlorodiiodomethane;
 bromodiiodomethane; and
 iodoform.

When chloramine or chlorine is used as a disinfectant, these compounds are usually present in very low
concentrations (fractional parts per billion) due to the low background presence of iodide in natural
waters.

Smith et al. (2010) compared the formation of DBPs from a number of iodine-based disinfectants (used at
the manufacturer’s recommended levels) to chlorination and chloramination under overdosing conditions.
The authors reported the following findings:

 the predominant THM formed during iodination was iodoform; chloroform predominated during
chlorination or chloramination;
 THM formation increased with pH during chlorination but was only slightly elevated at neutral
pH during iodination;
 use of iodine tincture was associated with higher levels of iodoform than with iodine tablets;
 iodoform formation with iodine tincture was 20–60% (on a molar basis) of chloroform formation
during chlorination;
 total organic iodide formation was twice that of total organic chlorine;
 iodoacetic acid, diiodoacetic acid, and other iodoacids were also formed with iodine tincture
treatment, but at levels < 11% of iodoform formation;
 a POU device combining an iodinated anion exchange resin with activated carbon post-treatment,
indicated minimal formation of iodinated DBPs, no iodine residual and N-nitrosamine formation
below 4 ng/L after the first few flushes of water.

3.6.2 Toxicological evaluations of iodinated disinfection by-products

Concern has arisen regarding iodinated DBPs as they are considered, on current evidence, to be of greater
toxicological concern than their brominated and chlorinated analogues (Richardson et al., 2007).
However, it should be noted that this view is predominantly based on findings from a very limited dataset
of in vitro cytotoxicity and genotoxicity assays, which are described below; the applicability of findings
from in vitro cytotoxicity and genotoxicity assays to humans has not been established at present. A

26
 Iodine as a drinking-water disinfectant

dataset of basic toxicological information on DBPs, as presented for iodine, is not available at the current
time. An exception to this is that iodoform has been tested in National Toxicology Program bioassays and
was not carcinogenic under test conditions (NCI, 1978).
Following the identification of iodoacids and iodinated THMs in chloraminated and chlorinated drinking
waters in the USA (section 3.6.1), Richardson et al. (2008) assessed the cytotoxicity and genotoxicity of
five iodoacids (iodoacetic acid, bromoiodoacetic acid, (Z)-3-bromo-3-iodo-propenoic acid, (E)-3-bromo-
3-iodo-propenoic acid, and (E)-2-iodo-3-methylbutenedioic acid) and two iodinated THMs
(dichloroiodomethane and bromochloroiodomethane) using in vitro assays with Chinese Hamster Ovary
cells.

The chronic cytotoxicity of the compounds measured in the study were ranked and compared to other
iodinated compounds by the authors. This resulted in a ranking order as follows:

iodoacetic acid > (E)-3-bromo-2-iodopropenoic acid > iodoform > (E)-3-bromo-3-iodo-propenoic acid >
(Z)-3-bromo-3-iodo-propenoic acid > diiodoacetic acid > bromoiodoacetic acid >
(E)-2-iodo-3-methylbutenedioic acid > bromodiiodomethane > dibromoiodomethane >
bromochloroiodomethane ~ chlorodiiodomethane > dichloroiodomethane.

With the exception of iodoform, the iodinated THMs were much less cytotoxic than the iodoacids.

Of the iodo-compounds analysed, 7 were genotoxic; their rank order was:

iodoacetic acid >> diiodoacetic acid > chlorodiiodomethane > bromoiodoacetic acid >
(E)-2-iodo-3-methylbutenedioic acid > (E)-3-bromo-3-iodo-propenoic acid >
(E)-3-bromo-2-iodopropenoic acid.

The authors reported that, in general, compounds containing an iodo-group had enhanced mammalian cell
cytotoxicity and genotoxicity as compared to their brominated and chlorinated analogues.

In the study described previously (section 3.6.1), Smith et al. (2010) compared the cytotoxicity of THMs
in four natural waters treated with different disinfectants (free chlorine, 20mM monochloramine, 20mM
iodine tincture, 72 mM elemental iodine, 172mM potassium iodide as iodine tablets, and a personal POU
treatment unit). THMs formed following treatment with iodine tincture were associated with between 19–
92 times higher cytotoxicity than for chlorination, with toxicity being driven by total organic iodine
content of the water samples. The cytotoxicity of THMs formed with the iodine tablet treatment was
around 40% lower than for treatment with iodine tincture. The authors estimated that from an exposure
perspective, chlorination may be preferable to iodination for long-term disinfection, where comparable
degrees of disinfection are achieved. Use of the personal POU treatment unit was also associated with
THM formation, with associated cytotoxicity approximately 10% of that with iodine tincture, but 6-fold
higher than for chlorination, with no iodine residuals apparent.

The authors highlight the importance of considering all iodinated DBPs when evaluating potential risks,
with measurement of iodoacids, and iodoforms as the dominant DBPs, following iodination. Diiodoacetic
acid and iodoacetic acid were formed at levels < 10% of iodoform following treatment with iodine

27
 Iodine as a drinking-water disinfectant

tincture. However, iodoacetic acid has greater cytotoxicity (> 2 times) in mammalian cells than iodoform,
and distinct from iodoform is genotoxic.

3.7 Summary
 Limited data (both from human and animal studies) suggest that the bioavailability of iodine from
foods and water is high, with inorganic iodine (usually in the form of iodide) being readily
absorbed (92%) from the small intestine. Iodine is rapidly distributed, including across the
placenta, and is stored in the thyroid gland for the synthesis of thyroid hormones (T4 and T3).
Excess iodine is mainly excreted in the urine, with very small amounts excreted in sweat, faeces
and exhaled air and secreted into human breast milk.
 In humans, several mechanisms help regulate iodine levels, to protect against toxicity; these
include reduced iodine uptake and preferential production of more heavily iodinated thyroid
hormones. Symptoms of acute iodine toxicity include vomiting and diarrhoea, metabolic acidosis,
seizure, stupor, delirium, and collapse. Sensitizing reactions include iodine mumps, iododerma,
and iodine fever.
 Chronic and sub-chronic iodine toxicity in humans includes disruption of thyroid function,
leading to hypothyroidism which can present with or without goitre, hyperthyroidism, and
changes in the incidence and types of thyroid malignancies. Responses of this type are associated
with a general high iodine intake or where intervention has taken place to compensate for iodine
deficiency. Measures of serum thyroid hormone levels (T4, T3 and TSH) are used as indicators of
iodine disturbances in humans.
 Iodine-induced hypothyroidism in humans has the potential to produce neurological effects
(delayed or deficient brain and neuromuscular development) in sensitive populations, particularly
in fetuses and new-born infants. Hyperthyroidism in humans has been associated with accelerated
growth.
 Dysfunction of the thyroid in humans has also been associated with reproductive disruptions
including changes in the menstrual cycle, menorrhagia, anovulation, spontaneous abortions,
stillbirths, and premature births.
 Iodine is not classifiable as a human carcinogen. Chronic iodine exposure has been associated
with metaplasia of the thyroid, considered to occur via a non-genotoxic mechanism.
Mutagenicity data for iodine are generally negative.
 Acute, sub-chronic, and chronic toxicity studies in animals support the findings from human
studies.
 The adverse effects associated with high levels of iodine intake are linked to the disruption of
thyroid hormone metabolism, the thyroid-pituitary axis, and the compensatory mechanisms that
exist to protect such metabolism against low or high levels of iodine intake. Previous exposures to
iodine and the complex effects of pre-existing thyroid conditions also influence the effects of
subsequent exposure.
 A threshold level for inducing thyrotoxicosis has not been established and available data are
inadequate to establish a dose-response relationship.
 Vulnerable members of the general population to iodine toxicity include pregnant and lactating
women, and neonates.

28
 Iodine as a drinking-water disinfectant

Due to limited available evidence, there are uncertainties regarding both the potential for formation of
iodinated DBPs and likely adverse effects at the concentrations predicted to be formed from use of iodine
as a drinking-water disinfectant. The applicability of findings from in vitro cytotoxicity and genotoxicity
assays to humans has not been established at present.

29
 Iodine as a drinking-water disinfectant

4. Environmental considerations
Environmental considerations are largely beyond the scope of this report; however, as noted in Table 8,
the impact of release of iodine into the environment to ‘non-target’ organisms should be considered.

Table 8: Environmental toxicity of iodine to ‘non-target’ species (USEPA, 2006)

Group of Common name Test compound L(E)C508 NOEC9 Acute toxicity

organisms (scientific name) rating
Fish Bluegill sunfish Iodine (99.8%) 0.61 mg/L 0.16 mg/L Highly toxic
(freshwater) (Lepomis
macrochirus)

Invertebrates Water flea Iodine (99.8%) 0.33 mg/L 0.09 mg/L Very highly
(Daphnia magna) toxic

8
LC50 – median lethal concentration; the dose required to kill half the members of a test population after a specified test duration.
EC50 – half maximal effective concentration; the effective concentration of a chemical that causes half of the maximum response
in a test population after a specified test duration.
9
No-observed-effect concentration.

30
 Iodine as a drinking-water disinfectant

5. Discussion and conclusions

The use of iodine for drinking-water disinfection, as with all water disinfectants, should be considered in
terms of risk versus benefit. Known issues of water quality in many parts of the world necessitate
additional measures to ensure potability. The risk of enteric infection should therefore be weighed against
the risk for, and severity of, acquiring thyroid disease from exposure to iodine over a short- and long-term
period of exposure, as well as alternative disinfection options.

Ideally a water treatment product (or combination of products) should be effective against all three classes
of pathogens, i.e. bacteria, viruses and protozoa. The evidence presented in this review indicates that
iodine is most effective against bacteria, has some effectiveness against viruses (particularly iodinated
resins) and comparatively less effectiveness against certain species of protozoa. Higher dosages and
longer contact times will be required when used as a disinfectant against protozoan cysts such as Giardia.
Iodine is not effective against Cryptosporidium oocysts at practical Ct values. At the time of this
publication, iodine has not been tested against WHO HWT performance targets and no evaluations have
been carried out on the health impacts in low-income settings with microbiologically contaminated
drinking-water.

From a disinfection perspective, iodine offers some advantages over chlorine:

 Water disinfection process requires less supervision, is simple and cost effective (although more
expensive than chlorine); and
 Iodine may provide superior disinfection to chlorine for water of poor quality. The reduced
overall reactivity of iodine prompts slower reactions with organic material and thus a lower
disinfectant demand. The low reactivity with organic nitrogenous contaminants results in
improved maintenance of residual iodine concentrations (Backer and Hollowell, 2000).

At the household level, there are a number of additional considerations beyond efficacy for determining
whether any product, including iodine, will protect health. Achieving health gains from HWT requires
products to be used correctly and consistently, and thus clear product information and use instructions are
important. In addition, user preferences, supply chains and availability, and cost are important factors to
consider. Products such as iodine and other drinking-water disinfectants which require a reliable supply
chain can be problematic in resource-limited settings where such systems are not in place.

The lack of knowledge on long-term toxic effects of iodine consumption impedes the use of iodine for
disinfection of municipal or community supplies. Considerable controversy exists about the maximal
“safe” dietary dose of iodine (in the range of 500 to 1000 µg/day in healthy adults) and the maximum
“safe” period of consumption for iodine treated water. Although a number of studies have been carried
out, the data are not adequate to establish a linear and temporal dose response between iodine intake and
altered thyroid function (Backer & Hollowell, 2000).

Current POU water disinfection devices that are both effective in terms of disinfection and can achieve
low residual levels (0.01 ppm) of iodine (such as triiodinated resins including a granular activated carbon
filter), are considered to be “safe” from a toxicological perspective to use for long periods of time in
euthyroid individuals (see Table 6). Assuming drinking water consumption in an adult of 2 L per day,

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 Iodine as a drinking-water disinfectant

residual iodine at this level would result in intakes of approximately 0.02 mg/day. This is well below the
low-end range of the recommended upper limit of 0.5 mg/day (CRN, 2013) even allowing for greater
consumption of drinking-water and/or intake of iodine from other sources. It is also low in comparison to
the AI of 0.15 mg/day for an adult recommended by EFSA (2014). However, for those disinfection
devices/methods that produce higher residual iodine levels (> 1 mg/L; such as iodine tablets, which leave
residual concentrations from 8–16 mg/L), intake of 2 L of purified water per day would result in intakes
of up to 32 mg/day, exceeding the recommended upper limit. Advice is given to limit the use of such
devices to a few months (Backer & Hollowell, 2000; WHO, 2011b). Current evidence (outlined in section
3.3) suggests that intake at levels of 18 mg/day and above are associated with changes to serum T4 and
TSH levels and TSH response to TRH (Gardner et al., 1988). Although no significant symptoms of
thyroid dysfunction were associated with these biochemical changes, this study was conducted over a
two-week period; hence, it is unclear if thyroid dysfunction would become apparent with prolonged
exposure. Supporting evidence from a study of Peace Corps volunteers (Pearce et al., 2002), which
showed a positive relationship between thyroid dysfunction and intake of iodine at 50 mg/day over 32
months, suggests that this would occur.

Iodine use for water disinfection is therefore not recommended for high-risk members of the population
including:

 Infants and young children;

 Pregnant women (the fetus is vulnerable to goitre);
 Individuals with known hypersensitivity to iodine;
 Individuals with a history or strong family history of thyroid disease; and
 Individuals from areas of severe iodine deficiency (may lead to hyperthyroidism).

In summary, the current evidence indicates that:

 As a drinking-water disinfectant, iodine can be most effective against bacteria. Iodine is less
effective against viruses and least effective against protozoa. Specifically, based on the
information presented in Table 5, iodine solutions are less effective against these two pathogen
classes compared to iodine resins.
 Effectiveness of iodine is impacted by the temperature, concentration, contact time, pH and
organic content of water; however, this is to a lesser extent than for chlorine. In addition, the
effectiveness of individual disinfectant products will vary according to manufacturing processes
and related quality management.
 Higher dosages and longer contact times for iodine will be required when used as a disinfectant
against protozoan cysts; iodine shows some effectiveness against Giardia cysts, but does not
appear to be effective against Cryptosporidium oocysts.

Iodine would not be recommended for use as a primary disinfectant due to the lack of knowledge on long-
term toxic effects and the availability of widely used, well-characterized disinfectants.

Use of POU applications of iodine as a water disinfectant may be appropriate under certain
circumstances. In POU applications, the potential toxicity associated with iodine consumption from
drinking-water will be variable depending on the method employed for disinfection and individual

32
 Iodine as a drinking-water disinfectant

susceptibility. When considering to use iodine as a drinking-water disinfectant compared to other water
disinfectants, recommendations should be considered in the context of overall benefits versus harm from
potential iodine toxicity and ingestion of contaminated water, as outlined below:

 For euthyroid individuals using resin-based disinfection devices that result in low residual
concentrations of iodine (e.g. those using resins with carbon filters), few adverse effects are
anticipated. Although there is insufficient evidence to support long-term use of devices
containing resin-based disinfectants and carbon filters, it is anticipated that these devices could be
used over extended periods of time. However, activated carbon filters should be replaced at
frequencies recommended by the manufacturer. In addition, care should be taken to ensure the
treated water is safely stored to prevent recontamination as the finished water will have no
residual disinfectant.
 For euthyroid individuals using other iodine disinfection techniques that result in higher residual
concentrations of iodine (e.g. solutions or tablets and resins without carbon filters), use should be
restricted to as short a period of time as possible. If longer term use of a disinfectant is needed,
another disinfectant should be utilized.
 For high-risk members of the population (noted on the previous page), water disinfection with
iodine is not recommended and an alternative disinfectant should be utilized. However,
disinfection should not be compromised due to the public health significance of microbiologically
unsafe water, and therefore if iodine is the only disinfectant available, use should be limited to as
short a time as possible, and an alternative disinfectant sought.

On the basis of limited effectiveness against viruses and particularly protozoa, as well as uncertainties
around the safety and toxicity, the use of iodine products may be appropriate for short-term use for
euthyroid individuals in targeted situations where the causative agent of disease is known. However,
where the causative disease agent is unknown, use by euthyroid individuals should ideally be combined
with another HWT method (e.g. with a filter) to provide comprehensive protection. The use of POU
devices should be appropriately approved or certified to ensure efficacy and safety.

33
 Iodine as a drinking-water disinfectant

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Appendix A: Methodology
Two initial literature searches were conducted in November 2013 as follows:

i) to update the toxicity assessment; and

ii) to update the efficacy assessment

The search strategy and terms are outlined in Box 1 and 2 respectively, below.

Box 1- Search strategy for toxicity assessment for iodine

((KEY(human OR animal) OR TITLE-ABS-KEY({in vitro} OR {in vivo})) AND

DOCTYPE(ar OR re) AND PUBYEAR > 2004) AND ((TITLE-ABS-KEY(toxicokinetic
OR irritation OR sensitisation) OR TITLE-ABS-KEY(genotoxicity OR mutagenicity OR
carcinogenicity) OR TITLE-ABS-KEY({Acute toxicity} OR {Repeat dose toxicity} OR
{Chronic toxicity}) OR TITLE-ABS-KEY({Reproductive toxicity} OR {Developmental
toxicity})) AND DOCTYPE(ar OR re) AND PUBYEAR > 2004) AND
(((CASREGNUMBER(7553-56-2) AND DOCTYPE(ar OR re) AND PUBYEAR > 2004))

Box 2- Search strategy for efficacy assessment for iodine

(TITLE-ABS-KEY(iodine) AND TITLE-ABS-KEY({drinking water} OR {potable

water}) AND TITLE-ABS-KEY(disinfection OR microorganism OR bacteria OR virus
OR protozoa OR antimicrobial OR bactericidal OR bacteriostatic)) AND PUBYEAR >
2004.

Searches were carried out using Scopus and Web of Knowledge databases. Titles and abstracts of journal
articles identified from the initial literature searches included 62 papers relating to iodine toxicity and 155
papers relating to iodine efficacy, which were reviewed to inform on their potential relevance to the
project. For those titles selected, which were included in the document, papers were obtained in full for
review to extract key data. Additional searches were carried out as needed, particularly for identification
of “grey” literature, earlier studies and during the period of document preparation (up to 16 December
2016).

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 Iodine as a drinking-water disinfectant

For more information, contact:

Water, Sanitation, Hygiene and Health

World Health Organization

20, Avenue Appia

1211 Geneva 27

Switzerland

E-mail: [email protected]

http://www.who.int/water_sanitation_health/water-quality/en/

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