Caballero B. (ed.) Encyclopaedia of Food Science, Food Technology and Nutrition. Ten-Volume Set

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IODINE

Contents

Properties and Determination

Physiology

Iodine-deficiency Disorders

Properties and Determination

MRL’Abbe

, Nutrition Research Division, Health

Canada, Ottawa, Ontario, Canada

Background

0038 Iodine is a blueish-black solid of the halogen family of

elements which readily sublimes to the deep violet I

vapor. The iodine concentration of human foods is

usually low and extremely variable. Foods naturally

high in iodine include seaweeds and marine fish. In

addition, iodine can be added to foods from sources

such as fertilizers, animal feed supplements, iodine-

containing sanitizers and disinfectants or through the

use of iodine-containing food additives and food col-

orants. Iodine is also added in many countries to

foods such as table salt for iodine fortification for

the prevention of iodine deficiency disorders (IDD)

or goitre. As iodine is volatile and can be easily oxi-

dized or reduced, care must be taken to prevent vola-

tility losses during analysis. The analyst must also be

aware of the chemical form and oxidation state of

iodine under various conditions to avoid losses.

Physical and Chemical Properties

0001 Iodine (I), atomic number 53, atomic weight 126.91,

is a nonmetallic element of the halogen family (group

VIIA) after fluorine (F), chlorine (Cl), and bromine

(Br) in the periodic table. Of these, iodine is the

heaviest and least electronegative. Solid iodine is a

bluish-black crystalline solid with a metallic luster in

the form of shiny flakes which can be readily crushed

into a fine powder. Iodine crystallizes in an ortho-

rhombic structure and is arranged in a unit cell of

eight atoms arranged as a symmetrical bipyramid.

0002 Solid iodine readily sublimes, as evidenced by its

pressure below melting point (Table 1). The vapor is

made up of diatomic iodine molecules (I

) which

dissociate readily at elevated temperatures. Iodine

vapor is characterized by its familiar violet color.

The specific gravity of I

vapor is approximately

nine times that of air. Solid iodine is only slightly

soluble in water and no hydrates form on dissolution,

although it readily dissolves in many organic solvents.

The color of iodine in solution varies with the solvent;

aliphatic hydrocarbons and carbon tetrachloride give

violet solutions, aromatic hydrocarbons give pink or

brownish pink solutions, and alcohols, water, ethers,

and some amines give brown colors.

0003The only stable isotope of iodine has a mass of 127.

There are 22 other isotopes having masses between

117 and 139, with 14 of these yielding significant

radiation. The electron configuration of the iodine

atom is 4d

. The chemistry of iodine is rather

complex as it can exist in a number of valence states,

with its principal oxidation states being 1, þ1, þ3,

þ5, and þ7 and an oxide IO

, with an oxidation

state of þ4. All these forms are thermodynamically

stable except the þ4 state. Iodine dissolves without

reaction in concentrated sulfuric acid and with con-

centrated nitric acid it reacts to form iodine pentox-

ide; in acidic solution it has mild oxidizing properties.

Iodine readily forms covalent iodides of metals such

as aluminum, tin, titanium, and many organic sub-

stances, but not with S, Se, and the noble gases, and

reacts only indirectly with C, N, O, and some noble

metals such as Pt. Iodine as a vapor or solid reacts

tbl0001Table 1 Selected physical properties of iodine

Property

Color Bluish black (solid)

Varies with solvent

(liquid)

Violet (gas)

Melting point,



C 113.6

Boiling point,



C 185 (liquid)

Crystal structure, 4 mol I

Orthorhombic

Density, g ml

1

(20



C) 4.93

Vapor pressure, kPa (25



C) 0.04133

Vapor pressure, kPa (113.6



C) 12.0655

Solubility, g kg

1

(25



C), water 0.34

Solubility, g kg

1

(25



C), benzene 164.0

Solubility, g kg

1

(25



C), chloroform 49.7

Solubility, g kg

1

(25



C), ethyl alcohol 271.1

Solubility, g kg

1

(25



C), n-hexane 13.2

Solid form except where indicated otherwise.

Color varies with solvent; see text for details.

3350 IODINE/Properties and Determination

readily with Mg, Ca, Al, Zn, Sn, Ni, and Fe, forming

the corresponding iodides. The metal iodides and

polyiodides are bases, whereas the iodine halides are

acids.

Sources of Iodine

0004 Iodine is one of the rarest nonmetallic elements on

earth. Although not abundant, iodine is distributed

widely in rocks, soils, waters, plants, animal tissues,

and foodstuffs. Of these, only a few substances char-

acteristically contain large quantities of iodine – these

being seaweeds, sponges, and corals, underground

waters from deep wells, and the vast natural deposits

of sodium nitrate found in northern Chile which con-

tain high amounts of iodine. Sea water contains the

largest total amount of iodine, mostly in the form of

iodide and iodates. Iodine is readily volatilized by the

action of sunlight and heat. Sunlight oxidizes iodide

to iodine and about 400 000 tons iodine of escape

from the oceans into the air each year. Atmospheric

iodine is then deposited on land and vegetation.

Many soils are low in iodine, particularly crystalline

soils exposed to glaciation and leaching, and soils

lacking humus cannot retain iodine. Heavy rains

also promote iodine-deficient soils, as does frequent

flooding of low-lying coastal regions. Areas of low

iodine and consequently a higher prevalence of

iodine-deficiency goiter have been located on every

continent throughout the world.

0005 Iodine has a wide range of chemical and related

industrial uses, some of which can make it into the

food supply. In 1996, approximately 39% of iodine

production was used for sanitation, pharmaceuticals

24%, heat stabilizers 13%, catalysts 9%, animal feed

7%, and other uses 8%.

Water and Soil

0006 Sea water is high in iodine and contains approxi-

mately 50 mgl

1

, mainly as iodide salts, although the

level in oceans can vary widely (Table 2). The level of

iodine in drinking water is much lower than that of

sea water and usually reflects the iodine content of the

rocks and soils in the region, although water from

deep wells can provide significant amounts of

iodine. Iodine in soil is in the form of iodide ions

which are readily oxidized by sunlight to volatile

elemental iodine, which is then released into the

atmosphere, thereby reducing soil levels in many

areas. Locally grown plants and crops and meat and

milk products usually reflect the iodine content of

soils and hence, foods from large parts of the world

are iodine-deficient unless fortified with iodine or

iodine is added to animal feeds or added during

food processing.

Dietary Sources

0007Foods The iodine concentration of human foods is

extremely variable. These variations are due to a

number of factors, including differences in the iodine

content and availability of iodine in the soil and water,

as described above. In addition, iodine is added

inadvertently to foods from sources such as fertilizers,

animal feed supplements, iodine-containing sanitizers

and disinfectants, or through the use of iodine-

containing food additives and food colorants. Iodine

is also added in many countries to foods such as table

salt for iodine fortification for the prevention of

iodine-deficiency disorders (IDD) or goiter.

0008Although the concentration of iodine in foodstuffs

is extremely variable, oilseed protein supplements

(soybean, cottonseed, linseed, and peanut) typically

contain 0.11–0.20 p.p.m. iodine, whereas cereal

grains range from 0.04 to 0.10 p.p.m. iodine. Milk,

milk products, eggs, and meat usually contain more

iodine than plant foods, although actual levels may

reflect iodine provided to the animals either naturally,

or through feed supplements, veterinary uses, or

during food processing.

0009The food sources containing the most iodine tend

to be marine products, although in recent dietary

surveys in some countries, dairy products and bakery

products were found to provide significant amounts

of iodine (Table 3). Ocean fish are especially rich in

iodine and may contain 300–3000 p.p.b. iodine

compared to 20–40 p.p.b. for freshwater fish. No

plants are known to preferentially, concentrate iodine

although seaweeds are particularly rich sources

tbl0002Table 2 Typical iodine levels in goitrogenous and

nongoitrogenous regions

Area

Goiter-free areas Endemic goiter

area

Drinking water (mgl

1

) 5–15

(4000–16 000)

0.1–2

Sea water (mgl

1

)50

Air (mgm

3

) 0.7 0.02

Soil (mgkg

1

) 300

<100

Dietary intakes (mgday

1

) 100–150

<25

Milk (mgkg

1

) 50–1000 <25

Bread (mgkg

1

)15 <5

Animal tissues (mgkg

1

) 100–400 <50

Areas of moderate to severe iodine-deficiency disorder (IDD) according

to the World Health Organization (1996) classification for prevalence

(severity) of IDD; median urinary iodine levels (mgl

1

) as mild (50–99),

moderate (20–49), or severe (<20).

In some areas, levels as high as 40–100 mgl

1

have been reported.

Final concentration in water after using iodine preparations for water

disinfection when used at recommended levels; recommended for short-

term use only.

Highest concentrations found in Chilean nitrate deposits (0.5–2 g kg

1

Intakes should be higher (200–300 mgday

1

) in the presence of large

amounts of goitrogens.

IODINE/Properties and Determination 3351

(50–4500 mgg

1

) due to the ocean environment in

which they grow. In Canada, milk and dairy products

contributed the greatest amounts to intake (239 mg

day

1

), followed by cereals (84 mgday

1

) and meat,

eggs, and fish (28 mg day

1

0010 As noted above, the iodine content of foodstuffs is

often modified by food-processing technology and

manufacturing practices. Iodine and its compounds

are used in a variety of food-related applications,

including nutrient fortification (e.g., iodized salt),

food additives (e.g., dough conditioners, maturing

agents, and food colorants), agricultural chemicals

(e.g., herbicides and fungicides), animal feed supple-

ments, and veterinary drugs (e.g., ethylenediamine

dihydroiodide, EDDI, which is 80% iodine and is

used to treat and/or prevent foot rot in cattle), and

sanitizers (e.g., iodophores) (Table 4).

0011Iodine-containing supplements in the feed of dairy

cattle, iodine-containing veterinary pharmaceuticals,

teat-dips and udder washes, as well as iodophores

used as sanitizing agents in dairy-processing establish-

ments can contribute to high iodine levels in dairy

products in countries where such practices are preva-

lent. Milk from dairy cows where no iodophor sani-

tizers or iodine-containing veterinary pharmaceuticals

are used usually contains less than 50 mgl

1

compared

to 200–800 mgl

1

or higher measured in some recent

surveys where these practices are common. Iodine

concentrations in milk are usually higher in winter

than summer, likely reflecting the greater use of

supplements and formulated feedstuffs compared to

pasture feeding. Very high levels of iodine in milk have

been observed with the feeding of relatively high

amounts of EDDI (which is 80% I). For example, the

tbl0003 Table 3 Comparison of iodine intakes in various countries by food group (mgday

1

)

a,b,c

Food group Canada

China

Milk and dairy products 239 91 1

Meat, fish, poultry, eggs 28 38 21

Breads, grains, cereal products 84 4 66

Fruits and fruit products 1 3 1

Vegetables, including potatoes 2 13 38

Fats and oils 2 1 NR

Nuts and legumes <1 0 5

Sugars and condiments 14 12 <1

Beverages Included above 17 5

Estimated total intake

(mg per person per day) 371 180 166

Values are for foods as consumed.

Comparisons by food groups are only approximate as the compositions of the various food groups are not exactly the same in different countries.

Does not include iodine from iodized salt, iodized oil, iodine supplements, or from drinking water.

Calculated from Fischer PWF and Giroux A (1987) Iodine content of a representative Canadian diet. Journal of the Canadian Dietetic Association 48: 24–27.

Calculated from Ministry of Agriculture, Fisheries and Food (2000) Food Standards Agency UK–1997 Total Diet Study^Fluorine, Bromine and Iodine. Food

Surveillance in Formation Sheet, 127. London: MAFF.

Average from five regions, from Hou X, Chai C, Qian Q, Lin G, Zhang Y and Wang K (1997). The study of iodine in Chinese total diets. Science of the Total

Environment 193: 161–167.

NR, not reported.

tbl0004 Table 4 Some examples of other sources of iodine contributing to food iodine content or to iodine intakes

Use Example (s)

Therapeutic drugs Preparations to treat thyroid disorders, radiopharmaceuticals and contrast media, topical

antiseptics (povidone-iodine solutions and ointments, betadine – an organically bound iodine),

potassium iodide used as an expectorant in cough and cold medications

Fortification Iodized salt, iodized oil

Food additives

Dough conditioners Potassium iodate (KIO

) in bread and bakery products

Food colorants/dyes Erythrosine (red dye #3; 2,4,5,7-tetraiodofluorescein)

Agricultural chemical residues 4

-hydroxy-3

-diiodobenzoic acid (herbicide)

Veterinary drug residues Ethylenediamine dihydroiodide (EDDI)

Animal feed supplements Provided as salt licks, or added as part of animal feed supplement. Dietary requirements for

livestock range from 0.14 (swine) to 0.5 (beef and dairy cattle) mg kg

1

Sanitizers Iodophores used in milking equipment, dairies, food processing, and restaurant grills

Water purification Effective at 0.5–1 p.p.m. (although water purification with iodine can often contribute

1000–2000 mg I day

1

)

3352 IODINE/Properties and Determination

iodine concentration in milk of cows fed 40 mg EDDI

was 361 mgl

1

, compared to 1559 mgl

1

in milk from

cows given 162 mg EDDI. In Scandinavian countries

(except Iceland), cows’ milk is a good source of iodine

because cattle fodder is iodinated by law.

0012 Iodine fortification and supplements Another

potential large contributor to iodine intakes is iodized

table salt, although iodized salt is not universally

available, nor is fortification mandatory in many

countries. According to the World Health Organiza-

tion in 1994, about 1600 million people were at risk

of IDDs because they live in iodine-deficient environ-

ments. Of these, 656 million had goiter and 43 mil-

lion had some degree of mental defect, including 11.3

million overt cretins. Endemic goiter is the most

visible sign of iodine deficiency, but impairment of

nervous system development and function is the most

serious consequence of iodine deficiency. Iodine defi-

ciency is still the world’s greatest single cause of pre-

ventable brain damage and mental retardation.

0013 In order to combat IDD, iodized table salt has been

used in many countries since the 1920s and can con-

tribute significant amounts of iodine to daily intakes.

A variety of other vehicles have also been used for

iodine supplementation of populations whose dietary

intakes of iodine are low. For example, injection with

iodized oil has been used in Papua New Guinea and

was found to be particularly effective for treatment of

goiter in remote mountain villages. In some countries

teas, rice, or oils have been fortified with iodine,

although problems have been encountered with non-

uniform intakes, stability, or bioavailability of some

of these forms. Before the advent of iodine fortifica-

tion, prevalence rates of endemic goiter in many parts

of the world were high and still remain so in areas

without universal salt fortification or iodine supple-

ment programs.

0014 Iodized salt In Canada, iodide is added at the rate of

76 mgIg

1

table salt while, for example, in Norway

iodide is added at 5, France 15, Finland 25, Sweden

50, USA 100, and in China at 12–30 mgIg

1

salt. In

Iceland salt is not iodized because iodine intakes are

already sufficiently high (300–350 mg day

1

) due to

the high consumption of salt-water fish. Intakes of

table salt also vary greatly in population surveys. In

Canada, some individuals use virtually no table salt,

compared to many others who consume more than

2 g day

1

. This contrasts greatly with countries such

as China where the consumption of table salt aver-

ages 10–30 g per person per day.

0015 Goitrogenic substances Goitrogenic substances are

substances that have antithyroid activity and interfere

with thyroid hormone production or utilization. The

most important goitrogens are thiocyanates, which

can compete with iodine for uptake into the thyroid

gland, especially when iodine intakes are low. Many

goitrogenic substances or their precursors are present

in plants of the Brassica spp. (the crucifer or mustard)

family and at least 10 other dicotyledonous plant

families. Brassica species such as cabbage, broccoli,

cauliflower, rutabaga, mustard, Brussels sprouts, and

turnip contain glucosinolates (previously called thio-

glucosides) which are hydrolyzed to form isothiocya-

nates, nitriles, and thiocyanates. About 100 different

kinds of glucosinolates are known to exist in the plant

kingdom, but only about 10 are present in Brassica;

high levels are also found in a number of seed meals,

e.g., some rapeseed and soybean meals. The first toxic

effects of isothiocyanates and other hydrolytic prod-

ucts from glucosinolates are goiter and a general

inhibition of iodine uptake by the thyroid.

0016Goiter and IDDs have also been attributed to cas-

sava consumption in many parts of the underdevel-

oped world. Cassava is a widely grown root crop

which accumulates cyanogenic glucosides, linamarin,

amygdalin, and lotaustralin. Linamarin accounts for

more than 80% of the cassava cyanogenic glucosides

and cyanide intoxication can occur when poorly

processed cassava meal is eaten.

0017In some parts of the world, water has been shown

as the cause of endemic goiter irrespective of its iodine

content, particularly water from shallow wells. Such

water is often grossly polluted and/or contains high

levels of nitrate or humic substances (and some of

their degradation products) which have also been

shown to be goitrogenic by blocking thyroidal

iodination.

Iodine Determination

0018Iodine analysis presents some of the most challenging

of analytical situations. Iodine is volatile and can be

easily oxidized or reduced. Thus, with iodine, care

must be taken to prevent volatile losses and the

analyst must be aware of the chemical form and oxida-

tion state of iodine under various conditions. Condi-

tions which are usually used to prepare samples and

dissolve the ash during the analysis of other trace elem-

ents of nutritional concern may not be appropriate for

iodine, so that iodine values are usually not available in

many multielement food surveys. When iodine data are

needed, a separate sample preparation phase specific-

ally designed for iodine is usually employed. In

addition, the content of iodine in diets and biological

samples is often very low (normally well below

<1.0mgg

1

; usually in the ng g

1

range), making

accurate determination of iodine a difficult task.

IODINE/Properties and Determination 3353

Sampling and Sample Preparation

0019 The complex nature of food samples compared to

biological matrices necessitates extra care in prepar-

ing food composites representative of different

geographic regions, seasons, food preparation (fresh,

canned, frozen), manufacturers, and lots. Care must

also be taken in thoroughly mixing, blending, and

homogenizing a representative sample. It is important

to transport and analyze samples as quickly as pos-

sible. Homogenized food and biological samples may

be stored in a refrigerator for a short time (1 or 2 days

prior to analysis). If samples are to be stored for

longer periods, samples should be appropriately

packaged and frozen at low temperatures (usually

20



Cto80



C) to minimize iodine loss or sample

degradation. As for all trace element analyses, appro-

priate storage containers should be used, although

iodine contamination during preparation is less of a

concern than for many other trace elements.

Analytical Quality Control and Reference Standards

0020 Prior to implementation of any analytical method,

method verification should form the first essential

step in the analysis of food or biological samples. In

its simplest form, method verification may consist of

low-level standard additions to representative food

samples along with the analysis of a certified standard

reference material of similar composition and analyte

levels as the sample of interest. Unfortunately, until

recently, many of the reference standards did not have

certified values for iodine, which severely limited the

choice of reference standards with similar matrix

properties and encompassing the range of iodine

seen in diet and biological samples. In recent years,

however, certified iodine values have been added for

many more reference materials (Table 5).

0021For implementation of new or previously untried

methods, more extensive preliminary testing is re-

quired, including a range of recovery testing, analysis

of a variety of reference standards, and comparison of

results with other established methods. Adoption of

new analytical techniques usually involves more

rigorous and involved analytical accuracy procedures

such as interlaboratory verification.

0022Choice of standards Volatilization losses are minim-

ized by maintaining iodine in an alkaline mixture or

in 2 mol l

1

. Iodic acid standards are more

stable than other forms of iodine such as sodium or

potassium iodide or iodate. Iodine solutions are

unstable in light and should be stored away from

extended exposure to white light. If sodium or potas-

sium iodide standards are used, stock solutions

should be prepared, stored at room temperature, pro-

tected from white light, and discarded after 30 days.

We have found that iodic acid stock solutions are

be stable up to 5 years when protected from light.

Diluted working standard solutions are normally

prepared fresh each week.

Analytical Techniques for Determination

of Iodine

0023There is a limited choice of methods for the determin-

ation of iodine in biological samples or food samples,

with the exception of certain seaweeds or thyroid

tissue which contain high concentrations of iodine.

The most common methods are based on catalytic

reactions, ion-selective electrodes, or neutron

tbl0005 Table 5 National Institute of Standards and Technology (NIST) reference standards suitable for analysis of iodine in food samples

and agricultural commodities

NIST identification Sample Certified value for I

(mgkg

1

)

SRM 1566a Oyster tissue 4.46 + 0.42

SRM 1549 Nonfat milk powder 3.38 + 0.02

RM 8435 Whole milk powder 2.3 + 0.4

RM 8415 Whole egg powder 1.97 + 0.46

SRM 1846 Infant formula (milk-based) 1.11 + 0.17

SRM 1548a Typical diet 0.759 + 0.103

SRM 1571 Orchard leaves Discontinued

RM 8418 Wheat gluten 0.060 + 0.017

RM 8414 Bovine muscle powder 0.035 + 0.012

RM 8433 Corn bran 0.026 + 0.006

RM 8436 Durum wheat flour 0.006 + 0.004

SRM 1577a Bovine liver Data for iodine not available

SRM 1567a

Wheat flour (0.0009)

SRM 1568a

Rice flour (0.0009)

Certified value from the NIST certificate. Values in parentheses are not certified but are provided by NIST for information only.

Reference material discontinued; replacement indicated by same SRM number followed by next letter designation, but replacement SRM is not yet

certified for iodine.

3354 IODINE/Properties and Determination

activation analysis. A few others such as spot tests are

useful in a limited number of situations.

0024 The method used in the analysis of samples should

be as sensitive as possible relative to the levels of

analyte in the samples under investigation. Prior to

the implementation of any iodine analysis, it is essen-

tial that the analytical method under consideration be

shown to be adequate for the range of food or bio-

logical samples to be analyzed. The limit of detection

is usually defined as the minimum concentration of

analyte that can be qualitatively detected, but not

quantitatively determined, under a predefined set of

conditions. Limit of quantification, on the other

hand, is the minimum concentration which can be

determined quantitatively with acceptable accuracy

and consistency. Quantities measured between the

two are usually referred to as ‘trace.’ Unfortunately,

in large surveys of food samples when multielement

analyses are performed, limits of quantification for

iodine are often not sufficiently sensitive to determine

accurately iodine levels in a wide range of food

samples. For example, in the 1995 US total diet

study, the limit of quantification for iodine was

0.002 mg 100 g

1

(20 ng g

1

), so that a large number

of samples had reported iodine values of zero. Food

iodine values are not currently available on the US

Department of Agriculture nutrient database.

Sample Preparation

0025 The two methods commonly used to destroy organic

matrix prior to iodine analysis are based on dry alka-

line combustion or wet acid digestion. The former are

usually done in open vessels, but can be done in a

closed-vessel microwave digestion apparatus. In gen-

eral, both methods are time-consuming, but necessary

prior to most analytical techniques. There are a

number of possible sources of iodine loss during the

sample decomposition phase, including evolution of

gaseous I

, absorption or adsorption on to surfaces,

or precipitation of undissolved material.

0026 Dry ashing typically involves treating samples with

2.5 volume 2 mol l

1

KOH in ethanol, drying, grad-

ual heating in a combustion oven to 600



C for 2 h,

cooling, dissolution (often ultrasonic dissolution is

necessary), followed by slurry filtration or centrifuga-

tion prior to analysis of the filtrate. Details can

be found in the Association of Official Analytical

Chemists method 935.14.

0027 For wet acid digestion, samples are digested in

borosilicate tubes in aluminum heating blocks or in

Kjeldahl flasks on Kjeldahl digestion racks with a

mixture of acids. Approximately 0.5–2 g of sample

is added to the flasks and an equal volume of water if

the sample is dry. Ten milliliters concentrated HNO

is added, followed by 20 ml HClO

and 5.0 ml

. Samples are covered and left overnight at

room temperature. Digestion is performed slowly

for the first 30 min with a cold finger inserted into

the top of the flask to prevent volatile losses of iodine

with the volatile nitrogen oxides. Thus the iodine is

refluxed back into the flask and oxidized by the large

excess of perchloric acid to nonvolatile iodates. If

insufficient perchloric acid is used, elemental iodine

will be lost. Once the evolution of nitrogen oxides

subsides, the remaining nitric acid is distilled off and

the temperature rises. Any lipid material will then be

converted to CO

and the rest of the perchloric acid

distilled off, resulting in a solution of pale straw color.

At this point dense sulfuric acid vapor will begin to

form and it is imperative that digestion ceases.

Samples are cooled and diluted to 100 ml with water

(final concentration 2 mol l

1

). Iodic acid

(HIO

) standards (1 ml each of 10, 50, 100, 250,

500, and 1000 p.p.b) and blanks are digested and

then analyzed with each batch of samples. Aliquots

of the digestate solution are then analyzed for iodine

using the iodine-catalyzed reduction of Ce

4þ

by As

3þ

A microplate modification of this colorimetric

method is described in the following section.

Determination of Iodine

0028Chemical or catalytic methods The spectrophoto-

metric determination of iodine is based on the cata-

lytic effect of iodide on the redox reaction between

the yellow ceric (IV) and arsenic (III) which yields the

colorless cerium (III) and arsenic (V), first reported by

Sandell and Koltoff in 1934. This is a two-step reac-

tion, where the rate of reaction is measured by the

determination of the loss of the yellow ceric (Ce

þ4

)

ions at 410 nm. Of the two steps, reaction (1) is

generally regarded as slow compared to the rapid

reaction (2). The net reaction (3) proceeds with ex-

treme slowness in dilute sulfuric acid at room tem-

perature, but is greatly increased in the presence of I



2Ce

þ4

þ 2I



! 2Ce

þ3

þ I

ð1Þ

þ3

þ I

! As

þ5

þ 2I



ð2Þ

Net 2 Ce

þ4

þ As

þ3

! 2Ce

þ3

þ As

þ5

ð3Þ

A couple of points are important to remember when

using this reaction. The catalytic coefficient of iodide

is a function not only of iodide concentration, but also

of the Ce

þ4

/As

þ3

concentration ratio, the chloride

concentration, and the sulfuric acid concentration.

The reaction is linear with respect to iodide when

there is a large ratio of As III to Ce IV. Chloride can

increase the velocity at low concentrations and also

inhibit the catalysis by iodide at high sodium chloride

concentrations, leading to large fluctuations in

IODINE/Properties and Determination 3355

background rates which interfere with iodine deter-

mination of food samples with widely differing salt

contents. This interference is overcome by using a large

excess of NaCl in the reaction mixture, typically 10%,

although this results in a slight loss of sensitivity.

0029 The iodine-catalyzed reduction of Ce

4þ

by As

3þ

colorimetric method has been semiautomated using a

Technicon autoanalyzer, which is no longer available.

More recent modifications have adapted the colori-

metric assay to 96-well microplate assay systems.

In the assay, 300 mlCe

4þ

(0.015 mol l

1

(NH

)

Ce(SO

)

2H

Oin2moll

1

), 300 mlAs

3þ

(0.015 mol l

1

in 2 mol l

1

), 300 ml

NaOH (10% NaOH) are added to each well. One

hundred microliters of sample or standard are added

to each microplate well at timed intervals. The plates

are mixed, centrifuged at 110 g for 40 s (IEC Centra

MP4R, Fisher Scientific, Nepean, ON) and incubated

for 35 min at 37



C. The color change of samples,

which is directly proportional to the concentration

of iodine in the sample, is measured at 410 nm using

a microplate spectrophotometer and compared to

the color change from the standard curve prepared

from the ashed standard solutions. Standard curves

used for food samples typically range from 10 to

1000 ng ml

1

0030 Alternative colorimetric procedures based on the

destruction of the intensely colored orange iron thio-

cyanate complex by nitrite in the presence of iodide

have also been employed and have the same range of

iodide sensitivity as the iodide catalyzed ceric/arsenic

reaction.

0031 The acid digestion followed by semiautomated colori-

metric determination of iodine has several advantages

for the analysis of large numbers of food samples. There

are few losses of iodine; typical recoveries of iodine

added to a variety of food composites are > 95%, and

similar recoveries are found for National Institute of

Standards and Technology (NIST) reference materials

within the range of the standard curve. An analyst can

typically digest 36 samples per day for 3 or 4 days

per week followed by colorimetric determination of

all sample digestates on a single day. The disadvantages

are that one must take appropriate safety precautions

when working with concentrated acids, a perchloric

acid fume hood is required, and the digestion must be

monitored continuously by the analyst.

0032 Iodide electrodes Iodine in water, milk samples, and

other liquids in which the only source of iodine is iodide



) can be determined using an ion-specific electrode.

In short, the protein in milk is removed by acid precipi-

tation, samples are filtered, and iodine in the filtrate is

determined by an iodide-specific electrode using the

standard addition procedure. Nickel nitrate is added

to reduce interferences to the iodide response. Ion-spe-

cific electrodes, however, are only suitable for liquid

samples, although samples do not have to be digested

prior to analysis. Because the gels get coated quickly

when analyzing samples such as milk and infant for-

mula, the electrodes must be carefully cleaned and

conditioned often to ensure accurate results. Full

details for the determination of iodide in ready-to-

feed milk-based infant formula using an ion-selective

electrode have been described in the Association of

Official Analytical Chemists method 992.24.

0033Spot tests Several rapid spot test kits have been

developed for the semiquantitative or qualitative esti-

mation of iodide in iodized table salt. In this proced-

ure the presence of iodine in salt is determined with a

standard starch solution, provided in a ready-to-use

formulation. In the standard test procedure, one drop

of test solution is added to a spoon of salt. The change

in color of the salt sample ranges from white to light

blue to dark violet depending on the iodine content of

the salt (usually classified as nil, 7, 15, or 30 p.p.m.)

when compared to the standard color chart provided

with the kit. These kits are useful in field situations

because results are available immediately, particu-

larly in underdeveloped countries where analytical

lab facilities are not readily available. Errors are usu-

ally associated with the subjective nature of the color

grading of the reaction.

0034Neutron activation analysis (NAA) When high sen-

sitivity and freedom from reagent blanks are desired,

neutron activation analysis (NAA) is often the

method of choice. In general, NAA is the best con-

firmation technique for trace element analysis as it is

independent of potential chemical interferences from

the sample matrix, although its widespread use in

food analysis is often limited due to high cost and

limited sample throughout capacity. NAA measures

radioactive iodine via gamma-ray spectroscopy after

a period of irradiation. Various forms of NAA have

been used, including: (1) radiochemical NAA; (2)

epithermal NAA, which permits nondestructive an-

alysis of samples; and (3) more recent modifications

such as preirradiation combustion (PC-NAA), which

permits extraction of the iodine from the sample

matrix without using strong chemical reagents,

followed by NAA.

0035For diet samples, conventional NAA of iodine is

critically interfered with by the strong radioactivities

Na,

Cl, and

K. In order to improve the detec-

tion limits of iodine, epithermal NAA using boron

nitride as a shield material has been used.

0036In a further refinement using PC-NAA, iodine

is first volatilized from the sample matrix by

3356 IODINE/Properties and Determination

combustion and adsorbed on charcoal after a series

of combustion steps. The segment of quartz contain-

ing the charcoal is sealed under vacuum and NAA

performed on the material. Detection limit is typically

50 ng and recovery using iodine-125 as a tracer

is usually 80–100%. Stable iodine is determined

following a 60-s irradiation to produce iodine-128.

After irradiation, samples and standards are counted

using a gamma-ray detector and sample concentra-

tion determined by comparing the peak heights of

iodine-128 in the standards and samples. Due to the

high equipment expense and low throughput (typic-

ally an analyst can only analyze two samples per day),

this method is not useful for routine applications,

although it may be useful for verification of results.

0037 Inductively coupled plasma–mass spectrometry (ICP-

MS) ICP-MS has also been used for iodine analysis.

Samples are extracted with tetramethyl ammonium

hydroxide (TMAH) at 90



C prior to analysis by ICP-

MS using metal compounds such as tellurium as an

internal standard. Although recoveries are usually

very good, ICP-MS, like NAA, is expensive and too

time-consuming for large-scale food surveys.

See also: Analysis of Food; Food Fortification;

Glucosinolates; Goitrogens and Antithyroid

Compounds; Hormones: Thyroid Hormones; Iodine:

Physiology; Iodine-deficiency Disorders; Spectroscopy:

Visible Spectroscopy and Colorimetry; Trace Elements;

Water Supplies: Water Treatment

Further Reading

Fischer PWF, L’Abbe

MR and Giroux A (1986) Colori-

metric determination of total iodine in foods by iodide-

catalyzed reduction of Ce

þ4

. Journal of the Association

of Official Analytical Chemists 69: 678–689.

Lauterbach A and Ober G (1995) Iodine and iodine com-

pounds. In: Howe-Grant M (ed.) Kirk-Othmer Encyclo-

pedia of Chemical Technology, 4th edn, vol. 14, pp.

709–736. New York: John Wiley.

MacKay GM, Points J and Pritchard E (eds) (1996) Trace

Analysis: A Structured Approach to Obtaining Reliable

Results. Cambridge: Laboratory of the Government

Chemist, Royal Society of Chemistry.

Norman B and Iyengar V (1998) The application of pre-

irradiation combustion and neutron activation analysis

technique for the determination of iodine in food and

environmental reference materials. Biological Trace

Element Research 63: 221–229.

Pennington JAT, Schoen SA, Salmon GD et al. (1995) Com-

position of core foods of the US Food Supply, 1982–

1991. III. Copper, manganese, selenium and iodine.

Journal of Food Composition and Analysis 8: 171–217.

WHO (1996) Trace elements in human nutrition and

health, Chapter 4: Iodine, pp. 49–71. Geneva: WHO.

Physiology

J A T Pennington, Division of Nutrition Research

Coordination, National Institutes of Health, Bethesda,

MD, USA

Absorption, Bioavailability, Transport, and

Storage of Iodine

0001Iodine in foods is primarily in the inorganic iodide



) form, which is readily absorbed form the stom-

ach and upper small intestine. Other forms of iodine

in foods are reduced to iodide before or after absorp-

tion. Absorbed iodine is rapidly cleared from the

blood plasma by the thyroid gland, kidney, salivary

glands, gastric mucosa, and lactating mammary

glands. Iodine intake in excess of body need is

excreted primarily through the urine.

0002The total amount of iodine in the body is about 10–

50 mg for an adult, and most of this is concentrated

in the thyroid gland. Thyroid-stimulating hormone

(TSH), from the anterior lobe of the pituitary gland,

stimulates the active transport of inorganic iodide

from the blood into the thyroid gland. Within the

thyroid cells, iodide is oxidized to iodine and com-

bined with tyrosine to form the thyroid hormones,

thyroxine (T

) and triiodothyronine (T

). The forma-

tion of thyroid hormones is also stimulated by TSH.

Thyroid hormones are stored in the thyroid gland

bound to the glycoprotein, thyroglobulin.

0003Proteolytic enzymes release the thyroid hormones

from thyroglobulin so that the hormones may diffuse

into the blood. In the blood, thyroxine is found pri-

marily bound to globulin and albumin. The secretion

of thyroid hormones into the blood is regulated by

TSH through a biofeedback system. When dietary

iodine is adequate, thyroid hormone is produced in

normal amounts at a low level of TSH; if dietary

iodine is limited, TSH secretion is increased, which

promotes iodine uptake by the thyroid. The thyroid

gland stores enough thyroid hormone to last several

months in the event that dietary iodine is not avail-

able. (See Hormones: Thyroid Hormones.)

Functions of Iodine in the Body

0004Iodine is a structural constituent of the two thyroid

hormones thyroxine (T

) and triiodothyronine (T

The chemical names of T

and T

are, respectively,

3,5,3

tetraiodothyronine and 3,5,3

triiodothyro-

nine. T

and T

are iodinated molecules of the essen-

tial amino acid tyrosine. Iodine accounts for about

65% of the weight of T

and 49% of the weight of T

The thyroid secretes T

and small amounts of T

. The

IODINE/Physiology 3357

principal role of these hormones is to regulate cellular

metabolism. The hormones are also required for

normal growth and bone maturation in children. In

infants, adequate supplies of thyroid hormone are

necessary for the development of the central nervous

system in the first 1–2 years of life. (See Children:

Nutritional Requirements; Infants: Nutritional

Requirements.)

0005 Thyroid hormones accelerate cellular reactions in

nearly all cells of the body, resulting in increased

oxygen consumption and an increase in basal meta-

bolic rate. The effects of the hormones are partially

the result of increases in enzyme activity, as many

enzymes are reported to be affected by T

. Within

body cells, thyroid hormones increase glycogen

synthesis, gastrointestinal uptake of glucose and

galactose, uptake of glucose by adipocytes, lipolysis,

oxidation of free fatty acids, and protein synthesis.

Thyroid hormones decrease serum cholesterol by

increasing the removal of low-density lipoprotein

from the blood.

Iodine Requirements

0006 Approximately 60–100 mg of iodine per day is needed

to produce an adequate supply of thyroid hormones.

The Recommended Dietary Allowances (RDAs) for

iodine in the USA are 40–50 mg per day for infants,

70–120 mg per day for children 1–10 years of age, and

150 mg per day for adolescents and adults. The USA

RDAs are 175 mg per day during pregnancy and

200 mg per day during lactation. Similar recommen-

dations for iodine intake are found in other countries.

Reported average daily intakes of iodine in the USA,

Australia, New Zealand, Canada, and European

countries generally meet or exceed these recommen-

dations.

0007 Iodized salt is a convenient and effective means

of meeting recommended intakes of iodine and

preventing iodine deficiency in countries where the

usual intake of iodine from food sources is low. In

many countries, the level of iodine in salt ranges from

0.002 to 0.005%; in the USA, it is 0.01%, or approxi-

mately 416 mg of iodine per teaspoon of salt. Thus,

one teaspoon of iodized salt provides 277% of the

adult RDA.

Dietary Sources of Iodine

0008 The inherent or natural iodine content of foods is

variable, depending upon the iodine content of soil

and water (for plant-based foods) and the iodine

content of feed (for animal-based foods). The highest

natural source of iodine is likely to be some species of

seaweed.

0009Milk and products containing milk may be high in

iodine due to the presence of indirect (i.e., uninten-

tional) food additives. The iodine in milk is derived

from ethylenediamine dihyroiodide (EDDI), a dietary

iodine supplement added to dairy cattle feed and from

iodophor solutions used as sanitizing agents on dairy

cattle and dairy equipment. The use and extent of use

of EDDI and iodophor solutions by the dairy industry

cause great variation in the iodine content of milk.

Seasonal and regional variations in the iodine content

of milk may reflect different feeding and supplemen-

tation practices. During the summer or in warmer

climates, dairy cattle may be pasture-fed. During the

winter or in colder climates, dairy cattle may be given

feed with EDDI supplementation. Feeding during

spring and autumn or in moderate climates may

reflect mixtures of pasture feeding and indoor feed

supplementation.

0010Other foods high in iodine are those with iodine-

containing food additives such as iodate dough con-

ditioners, the red food dye erythrosine, and iodized

salt. Iodate dough conditioners may be used in breads

and other grain products. Erythrosine (tetraiodo-

fluorescein) is 58% iodine (w/w) and may be present

in some red-colored candies, pastries, and breakfast

cereals. Although the concentrations of iodine in

foods with erythrosine are quite high, the iodine

from this source is only about 2–5% bioavailable.

Regulations regarding the mandatory or voluntary

iodization of salt and the level of iodization vary

among countries. In the USA, for example, both iod-

ized and noniodized salt are available in the market-

place, and the salt used by food manufacturers and by

restaurants is usually noniodized. In other countries,

the iodization of salt is mandated by government

regulations.

0011Iodine is also available in dietary supplements as

single supplements, in multiple mineral pills, and in

multiple vitamin–mineral pills. The level of iodine in

dietary supplements varies but is often 100% or more

of the RDA. Iodine may also be present in other

nutritional supplements and botanicals, especially if

they include dried extracts of seaweed, plants, or fish.

Iodine Intakes

0012Iodine intake varies widely among population

groups. Intakes may be less than 50 mg per day in

iodine-deficient areas, over 400 mg per day in areas

with iodized salt, and 1–5 mg per day or more in

coastal areas of Japan where seaweed is commonly

consumed. The main sources of dietary iodine for

adults in the 1982–1991 US Total Diet Studies

(TDS) were grain products (32% of iodine intake);

milk and cheese (18%); animal flesh, especially fish

3358 IODINE/Physiology

(13%); and desserts made with milk (10%). These

results for the US TDS were based on a yearly analysis

of 234 core foods for iodine content. Iodine intakes

from the 1982–1991 US TDS ranged from 170 mg per

day for infants to 386 mg per day for 25–30-year-old

men. Average intakes for the more recent (1990–

1991) TDS, were somewhat lower, ranging from

117 mg per day for infants to 317 mg per day for 14–

16-year-old males, and there seems to have been a

declining trend in iodine intake from 1982 to 1991.

Nonetheless, these more recent iodine intakes are well

above the RDAs without including iodine from dis-

cretionary salt (that added during cooking or at the

table). Thus, the TDS estimates of iodine intake

would be underestimated for individuals using iod-

ized salt. The use of a half a teaspoon of iodized salt

per day (iodized at the US level of 76 mg of iodine per

gram of salt) would add an additional 208 mgof

iodine.

Iodine Deficiency

0013 Dietary iodine deficiency leads to a decrease in

plasma T

and an increase in TSH. Under the influ-

ence of TSH, the thyroid becomes overactive, leading

to hypertrophy and hyperplasia of the gland. This is

known as ‘endemic goiter.’ Most individuals with

goiter are euthyroid (i.e., have normal thyroid levels).

Goiters range in size for modest enlargements to those

that are several times the normal size and are fre-

quently nodular in appearance. Large goiters may

cause obstruction of the trachea and esophagus, and

interfere with breathing and speaking. Prolonged

deficiency of iodine, resulting in decreased levels of

thyroid hormones, causes hypothyroidism or myx-

edema. The characteristics of this disease include

decreased metabolic rate, fatigue, cold intolerance,

weight gain, puffy face, dry skin, hoarse voice,

edema, easy bruising, drooping upper eyelids, mental

apathy, and problems with coordination. These

symptoms are reversible with iodine therapy. Iodine

deficiency during fetal development, infancy, or early

childhood may result in cretinism, a condition that

is not reversible and is characterized by retarded

growth, mental retardation, deafness, and neuro-

logical problems.

0014 In a few geographical areas, the development of

endemic goiter as a result of iodine deficiency may

be exacerbated by the ingestion of naturally occurring

compounds in foods, known as ‘goitrogens.’ Goitro-

gens act by impairing iodine uptake by the thyroid or

impairing the incorporation of iodine into tyrosine.

Foods that contain goitrogenic substances include

cassava, sweet potatoes, millet, and vegetables of the

genus Brassica such as cabbage, broccoli, and turnips.

The goitrogenic effect of these foods is not usually

apparent if the diet is adequate in iodine. (See Goitro-

gens and Antithyroid Compounds.)

0015The FAO/WHO estimates that more than 20% of

the world’s population lives in geographic areas that

are iodine-deficient. Iodine deficiency affects about

685 million people in Asia and the Pacific, 150 mil-

lion in Africa, almost 55 million in the Americans,

33 million in North Africa and the Near East, and 82

million in Europe. Goiter from iodine deficiency

affects about 200 million people world-wide. Preva-

lence rates for goiter of 5–20% are considered mild;

in some communities, in Africa, Asia, and Latin

America, more than 60% of the people have goiter.

Children and women are more vulnerable to iodine

deficiency than other population subgroups. About

26 million people have some degree of brain damage

and mental retardation, and six million are affected

by cretinism because of iodine deficiency.

Iodine Toxicity

0016Some individuals can tolerate very high levels of

iodine with no apparent side-effects, and iodine

intakes of up to 1 mg per day are probably safe for

the majority of the population but may cause adverse

effects in some individuals. Those who are most likely

to respond adversely to iodine are those who have

lived in areas of endemic goiter or who for other

reasons have a habitually low intake of iodine, those

with other thyroid disorders, and those who are sen-

sitive to iodine.

0017Exposure to excessive iodine has occurred through

foods, water supplies, drugs, dietary supplements,

topical medication, and/or iodinated contrast media

(used for X-rays). In the past, iodine-containing drugs

(most commonly potassium iodide solutions) have

been prescribed as expectorants for respiratory dis-

ease such as asthma, bronchitis, cystic fibrosis, and

chronic pulmonary obstruction. Such drugs have also

been prescribed for goiter, hyperthyroidism, rheuma-

tism, and syphilis. Amiodarone, an iodine-containing

drug, was prescribed for cardiac problems. The

medical literature reveals that excessive exposure to

iodine has resulted in thyroiditis, goiter, hypothyroid-

ism, hyperthyroidism, sensitivity reactions, or acute

responses for some individuals. Maternal iodine

exposure during pregnancy has resulted in goiter,

respiratory problems, enlarged hearts, and death of

infants.

0018Iodine-induced hyperthyroidism may occur in

some people receiving iodine supplementation. This

condition is referred to as Jod–Basedow disease.

These individuals may have underlying Graves’

disease (hyperthyroidism) and react adversely when

IODINE/Physiology 3359