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Iodine

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Brand names, Trade names
   1.6 Manufacturers, Importers
   1.7 Presentation, Formulation
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Properties of the substance
         3.3.1.1 Colour
         3.3.1.2 State/Form
         3.3.1.3 Description
      3.3.2 Properties of the locally available formulation(s)
   3.4 Other characteristics
      3.4.1 Shelf-life of the substance
      3.4.2 Shelf-life of the locally available formulation(s)
      3.4.3 Storage conditions
      3.4.4 Bioavailability
      3.4.5 Specific properties and composition
4. USES
   4.1 Indications
      4.1.1 Indications
      4.1.2 Description
   4.2 Therapeutic dosage
      4.2.1 Adults
      4.2.2 Children
   4.3 Contraindications
5. ROUTES OF ENTRY
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Other
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life, by route of exposure
   6.4 Metabolism
   6.5 Elimination, by route of exposure
7. PHARMACOLOGY AND TOXICOLOGY
   7.1 Mode of action
      7.1.1 Toxicodynamics
      7.1.2 Pharmacodynamics
   7.2 Toxicity
      7.2.1 Human Data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
   7.7 Main adverse effects
8. TOXICOLOGICAL AND BIOMEDICAL INVESTIGATIONS
   8.1 Sample
      8.1.1 Collection
      8.1.2 Storage
      8.1.3 Transport
   8.2 Toxicological analytical methods
      8.2.1 Tests for active ingredient
      8.2.2 Tests for biological sample
   8.3 Other laboratory analyses
      8.3.1 Biochemical investigations
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological or haemostasiological investigations
      8.3.4 Other relevant biomedical analyses
   8.4 Interpretation
   8.5 References (in section 13)
9. CLINICAL EFFECTS
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological
         9.4.3.1 Central nervous system (CNS)
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Others
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ear, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic
         9.4.12.1 Acid-base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Other
   9.6 Summary
10. MANAGEMENT
   10.1 General principles
   10.2 Relevant laboratory analyses
      10.2.1 Sample collection
      10.2.2 Biomedical analysis
      10.2.3 Toxicological analysis
      10.2.4 Other investigations
   10.3 Life supportive procedures and symptomatic/specific treatment
   10.4 Decontamination
   10.5 Elimination
   10.6 Antidote treatment
      10.6.1 Adults
      10.6.2 Children
   10.7 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from literature
   11.2 Internally extracted data on cases
   11.3 Internal cases
12. ADDITIONAL INFORMATION
   12.1 Availability of antidotes
   12.2 Specific preventive measures
   12.3 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)
    1. NAME

       1.1 Substance

           Iodine    (USAN)
             
           (Fleeger, 1994)

       1.2 Group

           Antiseptics and disinfectants (D08)/Iodine product/ (D08G)
          
           (ATC classification index, [WHO] 1992]

       1.3 Synonyms

           Eranol, Iodin (French), Iodine Colloidal, Iodine Crystals,
           Iodine Sublimed, Iodine-127, Iodio (Italian),
           Jod (German, Polish), Jood (Dutch), Iode, Iodum, Jodum, Yodo.

           (Reynolds, 1993) 

       1.4 Identification numbers

           1.4.1 CAS number

                 7553-56-2

           1.4.2 Other numbers

                 RTECS

                 NN 1575000

       1.5 Brand names, Trade names

           Betadine (Datlabs, Zimbabwe); Ethiodol (Savage, USA); 
           Guttajod (Blucher, Schering, Germany), Iodex (Smith Kline & 
           French, Australia, Switzerland etc) Fodex (Menley & James, 
           UK); Sclerodine (Ondee, Canada); Telepaque (Rhone Poulenc, 
           France); Urografin, Gastrofin (Rhone Poulenc, U.K.)
           
           (To be completed by each Centre using local data)

       1.6 Manufacturers, Importers

           DATLABS, Zimbabwe
           
           (To be completed by each Centre using local data)

       1.7 Presentation, Formulation

           Iodine is available in solid form, in solution, and in 
           tinctures, e.g.
           
           Povidone iodine antiseptic solution, surgical scrub 7.5%, 
           povidone iodine 200 mg pessaries, povidone antiseptic 
           ointment 100 mg/g.
           
           Tincture of iodine, USP, contains 2% cent iodine and 2.4% 
           sodium iodide diluted in 50% ethanol.
           
           Aqueous solutions of iodine are Strong Iodine Solution USP 
           (compound iodine solution, Lugol's solution) containing 5% 
           iodine and 10% potassium iodide, and Iodine Topical Solution 
           (USP) containing 2% iodine and 2.4% potassium iodide. Aqueous 
           Iodine Solution BP contains the same amount of free and 
           combined iodine per ml (130 mg/mL) as does the USP Strong 
           Iodine Solution. (Reynolds, 1993)
           
           Potassium iodide aqueous cough expectorant.
           
           Povidone-iodide (Betadine) is an organically bound iodide 
           compound containing 1% iodine in a water soluble base. Other 
           organically bound iodide compounds are undecoylium chloride, 
           diiodo hydroxyquin, tetraglycine hydroperiodide (60% iodine). 
           These organic iodide compounds release iodine slowly and have 
           a toxicity of one fifth of their iodine content (Haddad & 
           Winchester, 1983).
           
           Povidone iodine antiseptic solution and surgical scrub are in 
           5 litre containers, pessaries, ointment (see 1.7).

    2. SUMMARY

       2.1 Main risks and target organs

           Concentrated iodine is corrosive. Main risks in acute 
           exposure to high iodine concentrations are largely due to the 
           highly corrosive effect of iodine on the entire 
           gastrointestinal tract and resultant shock. If rupture occurs 
           mediastinitis or peritonitis develop.
           
           Target organs are mucous membranes of pharynx, larynx and 
           oesophagus for the concentrated iodine, and thyroid for the 
           diluted form as a systemic effect. Iodine is not a frequent 
           cause of toxicity in the amounts available in the household.
      
       2.2 Summary of clinical effects

           Ingestion of iodine may cause corrosive effects such as 
           oedema of the glottis, with asphyxia, aspiration pneumonia, 
           pulmonary oedema and shock, as well as vomiting and bloody 
           diarrhoea. The CNS , cardiovascular and renal toxicity 
           following acute iodine ingestion appear to be due to the 
           corrosive gastroenteritis and resultant shock. Vomiting, 
           hypotension and circulatory collapse may be noted following 
           severe intoxication.
           
           Eye
           
           Eye exposure may result in severe ocular burns.
           
           Cardiovascular
           
           Tachycardia, hypotension and circulatory collapse may be due 
           to the ingestion of concentrated corrosive iodine solutions.
           
           Respiratory
           
           Inhalation of iodine vapour may result in severe pulmonary 
           irritation leading to pulmonary oedema.  Oedema of the 
           glottis and pulmonary oedema have also resulted from oral 
           ingestion.
           
           Neurological
           
           Headache, dizziness, delirium and stupor may be noted 
           following severe intoxication.
           
           Gastrointestinal
           
           A severe corrosive oesophagitis and gastroenteritis 
           characterised by vomiting, abdominal pain and diarrhoea may 
           be noted following ingestion. The vomitus is blue if starch 
           is present in the stomach. A metallic taste may be noted.
           
           Dermatological
           
           Dermal application of strong iodine solutions may result in 
           burns.
           
           Chronic ingestion may result in iodism characterised from 
           acne form skin lesions and other skin eruptions.
           
           Cutaneous absorption may be significant and result in 
           systemic symptoms and death.
           
           Endocrine
           
           Hypothyroidism, as well as hyperthyroidism, has been 
           reported.
           
           Immunological
           
           Hypersensitivity reactions including angioedema and/ or serum 
           sickness-like reactions may be noted.
           
       2.3 Diagnosis 

           Clinical diagnosis is difficult, but iodine ingestion should 
           be considered in cases of corrosive injuries to the pharynx 
           and oesophagus.
           
           Iodine may or may not be seen in measurable levels in 
           biological fluids.

       2.4 First aid measures and management principles 

           Inhalation Exposure
           
           In case of inhalation move victim to fresh air. If victim is 
           not breathing, give artificial respiration, if breathing is 
           difficult give oxygen.
           
           Dermal Exposure
           
           In case of contact with iodine, immediately flush skin or 
           eyes with copious amounts of water for at least 15 minutes. 
           Remove and discard contaminated clothing and shoes. Keep 
           victim quiet and maintain normal body temperature. Effects 
           may be delayed so keep victim under observation.
           
           Oral Exposure
           
           In case of ingestion of concentrated iodine, do NOT induce 
           vomiting or gastric lavage. Call a physician or transport 
           victim to a medical facility.
           
           Sodium thiosulphate, 100 mL orally of a 1% solution, has been 
           recommended as an antidote because it immediately reduces 
           iodine to iodide. However iodine is mostly already 
           inactivated by combination with gastrointestinal contents.
           
           See Section 10 for management principles of iodine.

    3. PHYSICO-CHEMICAL PROPERTIES 

       3.1 Origin of the substance 

           Iodine is found in igneous rocks 3x10-5 % by wt. and in sea-
           water 5x10-8 % by wt.  Extracted from Chilian nitrate-bearing 
           earth (caliche) and from seaweed. (Windholz , 1983).

       3.2 Chemical structure 

           Structural Formula
           
           I-I
           
           Molecular formula
           
           I2
           
           Molecular weight
           
           253.81
           
           Chemical name
           
           Iodine

       3.3 Physical properties

           3.3.1 Properties of the substance

                 3.3.1.1 Colour

                         Blue greyish-black with a metallic crystalline 
                         sheen

                 3.3.1.2 State/Form
                                   
                         Solid brittle plates or small crystals

                 3.3.1.3 Description
    
                         Characteristic acrid odour.
                         
                         Iodine volatilises slowly at room temperature.
                         
                         Boiling point     185.24 C
                         
                         Melting point     113.60 C
                         
                         Solubility is 1 in 3500 of water, 1 in 8 of 
                         alcohol, 1 in 6 of carbon tetrachloride, 1 in 
                         30 of chloroform, 1 in 5 of ether, 1 in 125 of 
                         glycerol.  Very readily soluble in strong 
                         aqueous solutions of iodides.  A solution in 
                         alcohol, ether, or aqueous solutions of iodides 
                         is reddish-brown.  In chloroform, carbon 
                         tetrachloride, or carbon disulphide it is 
                         violet-coloured.
                         
                         (Reynolds, 1989)
                         
                         pH  No data available, but see 3.4.5.

           3.3.2 Properties of the locally available formulation(s)

                 To be completed by each Centre using local data
                 
       3.4 Other characteristics

           3.4.1 Shelf-life of the substance

                 The shelf-life of iodine solutions vary with the 
                 concentration.  The stability of alcoholic solutions of 
                 iodine increases as the iodide/free iodine ratio 
                 increases and for a given concentration, with increased 
                 strength of alcohol (Reynolds, 1989).

           3.4.2 Shelf-life of the locally available formulation(s) 

                 To be completed by each Centre using local data

           3.4.3 Storage conditions

                 Iodine topical solution should be stored in light-
                 resistant containers at a temperature not exceeding 
                 35 C and iodine tincture should be stored in air-tight 
                 containers.

           3.4.4 Bioavailability

                 To be completed by each Centre using local data

           3.4.5 Specific properties and composition

                 Degradation of iodine is associated with a fall in pH 
                 which might come down to pH = 2, (Reynolds, 1989).

    4. USES

       4.1 Indications

           4.1.1 Indications

                 In many countries culinary salt is iodized to prevent 
                 the development of goitre.
                 
                 In the pre-operative treatment of thyrotoxicosis to 
                 produce a thyroid gland of firm texture suitable for 
                 operation, it avoids the increased vascularity and 
                 friability of the gland with increased risk of 
                 haemorrhage.
                 
                 In the immediate treatment of thyrotoxic crisis.
                 
                 Its powerful bactericidal action is used for 
                 disinfecting unbroken skin before operation.  Iodine 
                 may also be employed as a weak solution for the first-
                 aid treatment of small wounds and abrasions, but it is 
                 rapidly inactivated by combining with tissue 
                 substances, and so delays healing.
                 
                 It has been applied topically in the treatment of 
                 herpes simplex (Reynolds, 1989).
                 
                 Iodine has been used in the treatment of dendritic 
                 keratitis (Grant, 1974).
                 
                 Iodine has been used in the purification of drinking 
                 water in case of emergencies (Osol, 1980). 
                 
                 Strong iodine solution: (Lugol's solution, aqueous 
                 solution of iodine, solution Iodi aquosa; compound 

                 iodine solution) contains in each 100 ml, 4.5 to 5.5 g 
                 of iodine, and 9.5 to 10.5 g of potassium iodide. This 
                 solution is used in the treatment of many conditions in 
                 which the action of iodine ion is desired such as 
                 thyrotoxicosis, keratoscleritis, keratitis associated 
                 with excessive keratin.
                 
                 Iodine-containing solutions are used as contrast media 
                 in radio-diagnosis.
                 
                 Potassium iodide has been used as a mucolytic agent.
                 
                 Radioisotopes: radioactive iodine finds its widest use 
                 in the treatment of hyperthyroidism and in the 
                 diagnosis of disorders of thyroid function.  The 
                 greatest use has been made of sodium iodide I131. 
                 Sodium iodide I123 is available for scanning purposes 
                 (Gilman et al., 1990).

           4.1.2 Description

                 Not relevant

       4.2 Therapeutic dosage

           4.2.1 Adults

                 Skin disinfectant
                 
                 10 to 25 mg/g often in combination with potassium or 
                 sodium iodide.
                 
                 Oral
                 
                  Lugol's solution
                 
                 Therapeutic dose range is 50 to 150 mg/day but up to
                 500 mg of iodine per day is often used, (Haynes, 1990).
                 
                 For the pre-operative treatment of thyrotoxicosis 
                 iodine may be given in the form of Aqueous Iodine Oral 
                 Solution BP or Strong Iodine Solution USP (both of 
                 which contain iodine 130 mg/mL) at a dose of 0.1 to 0.3 
                 mL three times a day for up to 10 days (Reynolds, 
                 1993).
                 
                  Cough mixture
                 
                 Potassium iodide aqueous expectorant is given at a dose 
                 of 300 mg every 6 hours. (Haynes, 1990)
                 
                  Purification of drinking water
                 
                 In case of emergencies, 5 to 10 drops of tincture to
                 a quart of water is both amoebicidal and bactericidal 
                 (Osol, 1980).
                 
                  Radioisotope dosages
                 
                 The effective dose in the treatment of hyperthyroidism 
                 by I131 differs for individual patients.  The optimal 
                 dose of I 131 expressed in terms of microcuries taken 
                 up per gram of thyroid tissue, varies in different 
                 laboratories from 80 to 150 microCi.  The usual total 
                 dose is 4 to 10 microCi (Haynes, 1990). Lower dosage I 
                 131 therapy (80 microCi/g thyroid) has been advocated 
                 to reduce the incidence of subsequent hypothyroidism 
                 (Cevallos et al., 1974).

           4.2.2 Children

                 No relevant data available.

       4.3 Contraindications 

           Iodine preparations should not be taken regularly during 
           pregnancy and lactation.
           
           Because iodine may cause burns on occluded skin, an iodine-
           treated wound should be covered with a light bandage. As 
           iodine and iodides can affect the thyroid gland, the 
           administration of such preparations may interfere with tests 
           of thyroid functions (Reynolds 1989; McEvoy, 1990).
           
           Potassium iodide should not be used in adolescent patients 
           because of its potential to induce acne and its effects on 
           the thyroid gland (Bouillon ,1988).
           
           Iodine or iodides should not be administered to patients with 
           a history of hypersensitivity to such compounds.

    5. ROUTES OF ENTRY

       5.1 Oral

           Toxic effects in humans can occur via accidental or  suicidal 
           poisonings, (Gosselin et al., 1984). Toxic effects of iodine 
           compounds resulting from ingestion of seaweed, mucolytic 
           expectorants or X-ray contrast are reported.
           
       5.2 Inhalation 

           With industrial exposure to vapour of iodine, it will be 
           absorbed from the lungs and converted in the body to iodide.

       5.3 Dermal 

           Topical iodine (especially with multiple applications) can be 
           absorbed, causing toxic effects.

       5.4 Eye 

           Eye drops can cause systemic toxic effects.

       5.5 Parenteral 

           Contrast media.

       5.6 Other 

           No data available.

    6. KINETICS

       6.1 Absorption by route of exposure  

           Oral
           
           Iodine appears to be inactivated by combination with 
           gastrointestinal contents. Absorption is poor due to rapid 
           conversion of iodine to iodide.
           
           (Reynolds, 1989; Gilman et al., 1990).
           
           Inhalation
           
           Iodine is absorbed from the lungs, converted to iodide in the 
           body, (ILO 1971). Pulmonary absorption of vapour may result 
           in systemic poisoning (Gosselin et al., 1984).
           
           Dermal
           
           Only very small quantities of iodine are absorbed through an 
           intact skin, (Reynolds, 1989). Iodine can be absorbed by 
           wounds and abrasions. Enhanced absorption occurs through 
           denuded skin, decubitus ulcers, mucosal surfaces with high 
           absorptive capacity (vagina), or large areas of intact skin, 
           (Dela Cruz et al., 1987; Vorherr et al., 1989; Prager & 
           Gardner 1979; Cosman et al., 1988).
           
           Eye
           
           Iodine can be absorbed when applied on the eye, (Geisthoevel, 
           1984).
           
           Parenteral
           
           No data available.

       6.2 Distribution by route of exposure 

           Oral
           
           When taken by mouth iodine is rapidly converted to iodide and 
           is stored in the thyroid as thyroglobulin, (Reynolds, 1989). 

           Iodine reaches the blood stream mainly in form of iodide, and 
           it is incorporated into the thyroglobulin form in the thyroid 
           gland, (Jones, 1977).
           
           Inhalation
           
           Iodine is readily distributed into the lungs.
           
           Dermal
           
           Distribution is poor due to low absorption through intact 
           skin. Enhanced distribution occurs through denuded skin.

       6.3 Biological half-life, by route of exposure 

           No data available.
     
       6.4 Metabolism 

           Iodine is an easily oxidisable substance. Food that is 
           present in the digestive tract, will oxidize iodine to iodide 
           which is not corrosive to the gastrointestinal tract, 
           (Reynolds, 1989; Gosselin et al., 1984).

       6.5 Elimination, by route of exposure 

           Iodine is excreted mainly in the urine, (ILO 1971) and in 
           smaller quantities in saliva, milk, sweat, bile and other 
           secretions, (Clayton & Clayton, 1981-1982). Renal iodine 
           clearance is related to glomerular filtration rate. Normal 
           renal excretion is 12000 g/day (Hunt et al. ,1980).
           
    7. PHARMACOLOGY AND TOXICOLOGY 

       7.1 Mode of action

           7.1.1 Toxicodynamics

                  Local
                 
                 Iodine precipitates proteins. The affected cells may be 
                 killed. The effect is similar to that of a corrosive 
                 acid.
                 
                  Systemic
                 
                 Acute inhibition of the synthesis of iodotyrosine and 
                 iodothyronine (Wolff & Chaikoff, 1984).

           7.1.2 Pharmacodynamics
     
                  Topical
                 
                 Iodine has bactericidal activity, e.g. a 1% tincture 
                 will kill 90% of bacteria in 90 seconds, a 5% tincture 
    
                 in 60 seconds and a 7% tincture in 15 seconds 
                 (Gershenfeld, 1968).
                 
                  Oral
                 
                 The primary function of iodine is to control the rate 
                 of cellular oxidation through its presence in the 
                 biosynthesis of iodated thyroid hormone.
          
       7.2 Toxicity 

           7.2.1 Human Data

                 7.2.1.1 Adults

                         The fatal dose is usually approximately 2 or 
                         3 g (Reynolds, 1989).

                 7.2.1.2 Children

                         No data available.

           7.2.2 Relevant animal data

                 No data available.

           7.2.3 Relevant in vitro data

                 No data available.

       7.3 Carcinogenicity

           There is no evidence as to whether iodine is carcinogenic or 
           not. However, connections have been established with 
           deliberate or inadvertent intake of radioactive elements or 
           their compounds that concentrate in certain organs or 
           tissues.  Thus intake of labelled iodine and derivatives 
           concentrating in the thyroid gland, have been known to give 
           rise to cancer in that organ (Harbison, 1980; Dukes, 1988).

       7.4 Teratogenicity 

           Iodides diffuse across the placenta. Infant and neonatal 
           death from respiratory distress secondary to goitre has been 
           reported in mothers taking iodides(Parmalee et al., 1940; 
           Galima et al., 1962).
           
           Chronic topical maternal use of povidone-iodine during 
           pregnancy has been associated with clinical and biochemical 
           hypothyroidism in the infant (Danziger et al., 1987). 
           Exposure to I 131 can damage or ablute the developing thyroid 
           of the human foetus. Hypothyroidism, either congenital or of 
           late onset, has been reported in at least 5 children whose 
           mothers were exposed to I 131 during pregnancy (Shepard, 
           1980)
          
       7.5 Mutagenicity

           No data available.

       7.6 Interactions

           No data available.

       7.7 Main adverse effects

           Endocrine system effects
           
           Iodine and iodides produce goitre, hypothyroidism as well as 
           hyperthyroidism. These effects have also been reported in 
           infants born to mothers who had taken iodides during 
           pregnancy (Reynolds, 1989).
           
           Side effects of iodine given for radioprotection
           
           In iodine-induced goitre and iodine-induced hypothyroidism, 
           special risk groups are foetus and neonates. Iodine-induced 
           hyperthyroidism special risk group are people living in 
           iodine deficient areas and people with a history of 
           hyperthyroidism, (Bouillon, 1988). Extrathyroidal side 
           effects are gastrointestinal complaints (nausea, pain), taste 
           abnormalities, cutaneous and mucous membrane such as 
           irritation, rash, oedema (including face and glottis), 
           allergic-like reactions such as fever, eosinophilia, serum-
           sickness-like symptoms, vasculitis. Special risk groups are 
           patients with hypocomplementic vasculitis, (Bouillon, 1988).
           
           Allergic effects
           
           Whether iodine is administered topically or systematically, 
           iodine and iodides can give rise to allergic reactions: 
           urticaria, angioedema, cutaneous haemorrhage or purpuras, 
           fever, arthralgia, lymphadenopathy and eosinophile, acne-form 
           or severe eruptions.
           
           Iodism effects
           
           A mild toxic syndrome called iodism results from repeated 
           administration of small amount of iodine. Iodism is 
           characterised by hyper-salivation, coryza, sneezing, 
           conjunctivitis, headache, laryngitis, bronchitis, stomatitis, 
           parotitis, enlargement of the submaxillary glands, skin 
           rashes and gastric upsets, (Reynolds, 1989, Gosselin et al, 
           1984). In rare cases jaundice, bleeding from mucous membranes 
           and bronchospasm may occur. Inflammatory states may be 
           aggravated by these adverse reactions, (Bouillon, 1988).
           
           Gastrointestinal effects
           
           Acute effects due to ingestion of iodine are mainly due to 
           its corrosive effects or action which arises at least in part 

           from oxidizing potential of this element on the 
           gastrointestinal tract. Symptoms include a metallic taste, 
           vomiting, abdominal pain, and diarrhoea. Oesophageal 
           stricture may occur if the patient survives the acute stage, 
           (Reynolds, 1989; Gosselin et al., 1984).
           
           Cardiovascular and respiratory effects
           
           Death may occur due to circulatory failure, oedema of the 
           glottis resulting in asphyxia, aspiration pneumonia, or 
           pulmonary oedema, (Reynolds, 1989, Sittig 1981).
           
           Kidney effect
           
           Anuria may occur 1 to 3 days after exposure, (Reynolds, 
           1989).
    
    8. TOXICOLOGICAL AND BIOMEDICAL INVESTIGATIONS

       8.1 Sample 

           8.1.1 Collection

           8.1.2 Storage

           8.1.3 Transport

       8.2 Toxicological analytical methods

           -     Both amperometric titration and leucocrystal violet 
           (LCV) colorimetric methods give acceptable results when used 
           to measure free iodine in drinking water, (National Research 
           Council 1980).
           
           -     With the aim of indicating environmental pollution 
           effects on humans, none destructive activation analysis was 
           applied to 382 normal Japanese hair samples, (Ohmori et al, 
           1981). 

           8.2.1 Tests for active ingredient

           8.2.2 Tests for biological sample

       8.3 Other laboratory analyses

           8.3.1 Biochemical investigations

                  Blood
                 
                 Elevated serum transaminases and bilirubin 
                 concentrations are reported (Lavelle et al., 1975; 
                 Peitch & Meakins, 1976).  Serum creatinine levels up to 
                 3.5 mg/dL have been reported by Dela Cruz et al., 
                 (1987).  Elevated TSH concentrations and low T4 
                 

   
                 concentrations has been demonstrated in neonates with 
                 topical povidone-iodine (Cosman et al., 1988).
                 
                  Urine
                 
                 No data available.
                 
                  Other
                 
                 No data available.
                 
           8.3.2 Arterial blood gas analyses

                 Severe metabolic acidosis is reported in topically-
                 treated burn patients (Peitsch & Meakins, 1976).

           8.3.3 Haematological or haemostasiological investigations 

                 No data available.

           8.3.4 Other relevant biomedical analyses

       8.4 Interpretation

       8.5 References (in section 13)
    
    9. CLINICAL EFFECTS

       9.1 Acute poisoning 

           9.1.1 Ingestion

                 Ingestion of iodine may cause corrosive effects such as 
                 oedema of the glottis, with asphyxia, aspiration 
                 pneumonia, pulmonary oedema and shock, vomiting and 
                 bloody diarrhoea.  The CNS, cardiovascular and renal 
                 toxicity following acute iodine ingestion appear to be 
                 due to the corrosive gastroenteritis and resultant 
                 shock.  Vomiting, hypotension and circulatory collapse 
                 may be noted following severe intoxication.

           9.1.2 Inhalation 

                 Inhalation of iodine vapour is very irritating to 
                 mucous membranes. Headache, dizziness, delirium, 
                 collapse and stupor, death due to circulatory collapse, 
                 asphyxia from oedema of glottis, aspiration pneumonia 
                 or pulmonary oedema has been reported. Occasionally 
                 haemorrhagic nephritis may occur within 1 to 3 days, 
                 oesophageal and pyloric stenosis have been reported, 
                 (Gosselin et al., 1984).
                    
           9.1.3 Skin exposure 

                 Skin contact with iodine may give rise to 
                 hypersensitivity reaction, fever and skin eruption. 
                 Death following skin contact covering one third of body 
                 surface is reported to have occurred, (Gosselin et al., 
                 1984).

           9.1.4 Eye contact 

                 Iodine vapour causes irritation and lachrymation in 
                 human eyes, (Grant, 1974).

           9.1.5 Parenteral exposure 

                 Injection of iodine compounds may cause sudden fatal 
                 collapse (anaphylaxis) as a result of hypersensitivity. 
                 Symptoms are dyspnea, cyanosis, fall of blood pressure, 
                 unconsciousness and convulsions, (Dreisbach & 
                 Robertson, 1987).

           9.1.6 Other 

                 No data available.

       9.2 Chronic poisoning 

           9.2.1 Ingestion 

                 Repeated administration of small amounts of iodine may 
                 result in a mild toxic syndrome called "iodism". It is 
                 characterised by hyper-salivation, coryza, sneezing, 
                 conjunctivitis, stomatitis, parotitis, enlargement of 
                 the submaxillary glands, and skin rashes (Barker & 
                 Wood, 1940; Ehrich & Seifter, 1949).
                 
                 Hypotension, tachycardia, cyanosis and signs of shock 
                 are frequent symptoms of iodine ingestion. (Gosselin et 
                 al., 1984).
                 
                 Iodated glycerol used as a mucolytic expectorant in the 
                 treatment of respiratory disorders inhibited the 
                 biosynthesis of thyroid hormone and induced 
                 hypothyroidism (Drinka & Nolten, 1988; Gommolin, 1987).
                 
                 Amiodarone, an iodine rich drug widely used in the 
                 treatment of tachyarrhythmias, represents one of the 
                 most common sources of iodine-induced thyrotoxicosis 
                 (Martino et al., 1987; Regouby et al., 1985).
                 
                 Tablets of seaweed, sold over the counter, is one of 
                 the less common sources of iodine-induced 
                 hyperthyroidism (Shilo & Hirsch, 1990).

           9.2.2 Inhalation 

                 No data available.

           9.2.3 Skin exposure 

                  Intact skin
                 
                 Irritant contact dermatitis caused by povidone-iodine 
                 has been reported, (Okano, 1989). Liberal application 
                 of the tincture or povidone-iodine to the skin resulted 
                 in significant plasma and urine iodine levels and may 
                 cause systemic iodine toxicity (Luckhardt et al., 1920; 
                 Smerdely et al., 1989; Pyati et al., 1977; Chabrolle & 
                 Rossier, 1978; Coakley et al., 1989; L'Allemand et al., 
                 1987; Dantzigen et al., 1987; Schoenberger & Grim, 
                 1982).
                 
                  Injured skin
                 
                 Continuous postoperative wound irrigation with 
                 povidone-iodine resulted in death of a patient. Toxic 
                 manifestations of systemic iodine absorption appeared 
                 to cause the death, (D'Auria et al., 1990; Glick et 
                 al., 1985).
                 
                 Application of povidone-iodine on skin burns may cause 
                 systemic iodine toxicity (Lavelle et al., 1975; Peitsch 
                 & Meakins, 1976).

           9.2.4 Eye contact 

                 Iodine-containing eye drops caused hyperthyroidism 
                 (Geisthoevel, 1984).
                 
           9.2.5 Parenteral exposure 

                 Iodine-containing contrast media may cause 
                 hyperthyroidism; the most frequent thyroid disorders, 
                 usually of a temporary nature, occur after choledochal 
                 contrast media (Steidle, 1989). In premature infants 
                 they cause hypothyroidism (L'Allemand et al., 1987).

           9.2.6 Other 

                 No data available.

       9.3 Course, prognosis, cause of death 

           If the patient survives 48 hours after the ingestion of 
           iodine, recovery is likely, although stricture of the 
           oesophagus or pyloric sphincter may be a complication, 
           (Dreisbach & Robertson 1987). It is probable that the 
           pathological changes recorded in fatal cases of iodine 
           poisoning and attributed to the systemic effects of iodine 

           are largely the result of shock due to massive loss of fluid 
           from the gastrointestinal tract and tissue hypoxia (Gilman et 
           al.,1990).

       9.4 Systematic description of clinical effects 

           9.4.1 Cardiovascular 

                 Cardiovascular effects are not due directly to iodine 
                 or iodide. Hypotension, tachycardia circulatory 
                 collapse may occur secondary to corrosive 
                 gastroenteritis due to ingestion of highly concentrated 
                 iodine solutions. In acute iodine inhalation, 
                 hypotension and tachycardia have been reported, 
                 (Gosselin et al., 1984).

           9.4.2 Respiratory 

                 Inhalation of fumes leads to irritation of mucous 
                 membranes of the respiratory tract, which may result in 
                 asphyxia. Oedema of the glottis from ingestion was 
                 reported in early literature as a frequently mentioned 
                 cause of death, (Finkelstein & Jacobi, 1937).
                 
                 Pulmonary oedema and tachypnoea have been reported 
                 following ingestion of an unspecified large quantity of 
                 Lugol's solution, (Dyck et al., 1979).

           9.4.3 Neurological 

                 9.4.3.1 Central nervous system (CNS) 

                         Headache, dizziness and delirium have been 
                         reported in severe intoxications.  Altered 
                         sensorium (agitation, confusion, 
                         hallucinations) have occurred in association 
                         with elevated serum iodine concentrations, 
                         (Alvarez, 1979; Gosselin et al., 1984).
                         
                         Continued administration of iodine may lead to 
                         mental depression, nervousness and insomnia 
                         (Reynolds, 1989).

                 9.4.3.2 Peripheral nervous system 

                         No data available.

                 9.4.3.3 Autonomic nervous system 

                         No data available.

                 9.4.3.4 Skeletal and smooth muscle 

                         No data available.

           9.4.4 Gastrointestinal 

                 Excessive ingestion of iodine solutions can lead to 
                 gastrointestinal irritation, vomiting and ulceration at 
                 various levels of the upper gastrointestinal tract. 
                 Late oesophageal and pyloric stenosis have been 
                 reported, (Gosselin et al., 1984).
                 
                 If the stomach contains starch the emesis is coloured 
                 blue.

           9.4.5 Hepatic 

                 Elevated serum transaminases and bilirubin 
                 concentrations have been reported occasionally in 
                 patients with elevated serum iodine concentrations, 
                 (Lavelle et al., 1975; Peitsch & Meakins, 1976).

           9.4.6 Urinary 

                 9.4.6.1 Renal 

                         Poisoning is manifested by serum creatine and 
                         levels up to 3.5 mg/dL (309 mmol/L) has been 
                         reported, (Dela Cruz et al., 1987). The renal 
                         lesions, which sometimes resemble acute 
                         tubularnecrosis, may be exacerbated by 
                         haemolytic anaemia, (Gosselin et al., 1984).
                         
                         Nephrotoxicity by iodine contrast media is 
                         reported by  Cacoub et al., (1987).

                 9.4.6.2 Others 

                         No data available.

           9.4.7 Endocrine and reproductive systems 

                 Transient hypothyroidism characterised by elevated 
                 urinary iodide concentrations, elevated serum iodine 
                 concentrations, elevated TSH concentrations, and low T4 
                 concentrations have been demonstrated in povidone-
                 iodine exposed mothers and their infants (L'Allemand et 
                 al., 1987).
                 
                 Iodine induced thyrotoxicosis is a condition that may 
                 develop in older patients with long-standing iodine 
                 deficiencies who receive high doses of iodine 
                 (Kobberling et al., 1985; Fradkin, 1983; Klein & Levey, 
                 1983).
                 
                 Iodine containing drugs caused thyrotoxic crisis 
                 (Mackenroth, 1990).
                 
                 Excessive iodine intake can cause thyroid autoimmunity 
                 in endemic goitre, (Boyages et al., 1989).
                 
                 Organically bound iodine in the form of iodinated 
                 glycerol used as a mucolytic expectorant can inhibit 
                 the biosynthesis of thyroid hormone and induce 
                 hypothyroidism, (Drinka & Nolten, 1988).
                 
                 Hypothyroidism has also been described in neonates 
                 treated with topical povidone-iodine (Cosman et al., 
                 1988). Topical iodine containing antiseptics may induce 
                 hypothyroidism in very-low-birthweight infants, 
                 (Smerdely et al., 1989). Multiple applications of 
                 povidone iodine in pregnancy, and lactation caused 
                 transient congenital hypothyroidism in a 6 week old 
                 girl, (Danziger et al., 1987).
                 
                 Iodine in contrast agents and skin disinfectants is the 
                 major cause for hypothyroidism in premature infants 
                 during intensive care, (L'Allemand et al., 1987).
                 
                 Iodated glycerol, an organic form of iodine, prescribed 
                 as a mucolytic-expectorant induced a mild 
                 hypothyroidism in a patient with a previous history of 
                 severe potassium iodide-induced hypothyroidism.
                 
                 Amiodarone, an iodine-rich drug widely used in the 
                 treatment of tachyarrhythmias, represents one of the 
                 most common sources of iodine-induced thyrotoxicosis. 
                 It developed not only in patients with underlying 
                 thyroid disorders, but also in subjects with apparently 
                 normal thyroid gland. Thyrotoxicosis occurred either 
                 during treatment with or at various intervals after 
                 withdrawal of amiodarone. Classical symptoms were often 
                 lacking, the main clinical feature being a worsening of 
                 cardiac disorders, (Martino et al., 1987).
                 
                 Tablets of seaweed, sold over the counter, is a real 
                 source of iodine. A 72-year-old female developed 
                 hyperthyroidism while ingesting these tablets. After 
                 stopping, the symptoms of hypothyroidism disappeared, 
                 (Shilo & Hirsch, 1990).
                 
                 Continuous povidone-iodine irrigation caused iodine 
                 toxicity with symptoms of metabolic acidosis, changes 
                 in mental status and the patient died (Glick et al., 
                 1985).
                 
                 Administration of iodine containing eye-drops used as a 
                 cataract treatment caused hyperthyroidism (Geisthoevel, 
                 1984).

           9.4.8 Dermatological 

                 A case of fatal dermatitis following the use of a 2.5% 
                 solution of resublimated iodine in pure industrial 
                 alcohol before a surgical operation has been reported. 
                 The reaction was thought to be due to idiosyncrasy to 
                 iodine. Skin disinfection with iodine has caused goitre 
                 and hypothyroidism in 5 of 30 newborns under intensive 
                 care (Bouillon, 1988).
                 
                 Prolonged exposure to tincture of iodine can induce 
                 superficial necrosis. At least one death has been 
                 reported consequent to extensive skin involvement. 
                 Solutions of iodine applied to the skin should not be 
                 covered with occlusive dressings.
                 
                 Topical application of povidone-iodine on burn patients 
                 may lead to increased iodine/iodide absorption (Lavelle 
                 et al., 1975) and the development of a metabolic 
                 acidosis, renal failure and an altered mental status 
                 although a cause and effect relationship has not been 
                 definitely established.
                 
                 The older literature reports systemic symptoms which 
                 occurred immediately to 24 hours later, rarely 
                 following cutaneous application of one-half to one 
                 normal strength iodine tincture. Symptoms included 
                 fever, diarrhoea, pain, headache and delirium. Skin 
                 eruptions included urticaria to erythema to exfoliative 
                 dermatitis. Mortality was 47% in those 15 cases 
                 reported (Seymour, 1937).
                 
                 Repeated applications of iodophors may cause contact 
                 dermatitis. Allergic reactions occur 12 to 20 hours 
                 after application (Harvey, 1985; Kudo et al., 1988).

           9.4.9 Eye, ear, nose, throat: local effects 

                 Exposure to iodine vapour may cause burning in the 
                 eyes, blepharitis, and severe ocular burns (Finkelstein 
                 & Jacobi, 1937).
                 
                 Iodine vapour may cause rhinitis.
                 
                 Stomatitis and pharyngitis may result from exposure to 
                 iodine vapour or solutions and mucous membranes are 
                 coloured brown. (Finkelstein & Jacobi, 1937).

           9.4.10 Haematological 

                  Neutropenia has been reported in association with 
                  elevated serum iodine concentrations, (Alvarez, 1979).
                  
                  Thrombotic thrombocytopenic purpura has been observed 
                  after repeated administration of small amounts of 
                  iodine, (Ehrich & Seifter, 1949)
                  
                  Haemolysis has also been reported (Dyck et al., 1979).

           9.4.11 Immunological 

                  Reactions to iodine may occur acutely or after chronic 
                  use and may be characterised by coryza, headache, 
                  salivary gland pain, conjunctivitis, fever or skin 
                  reactions (urticaria, acneform, eruptions, erythema, 
                  bullous, ioderma). Oral and intravenous iodine 
                  containing radio-contrast media (e.g Telopaque (R); 
                  I125, I131) may cause iodine hypersensitivity reaction 
                  as well as anaphylactic type reactions, (Crocker & 
                  Vadam, 1963).

           9.4.12 Metabolic 

                  9.4.12.1 Acid-base disturbances

                           Metabolic acidosis may be associated with 
                           iodine toxicity. There is an increased anion 
                           gap due to elevated serum lactate levels (47 
                           micromol/L) (Dyck et al., 1979; Dela Cruz et 
                           al., 1987)

                  9.4.12.2 Fluid and electrolyte disturbances 

                           Elevated serum sodium (hypernatraemia) (156 
                           mEq/L) has been reported (Dela Cruz et al., 
                           1987).
                           
                           Hyperchloremia (127 mEq/L) has also been 
                           reported but probably represents a spurious 
                           elevation due to interference in the assay by 
                           iodine (Dela Cruz et al., 1987).
                           
                           Elevations in calculated osmolarity (340 in 
                           Osm/L) have also been reported (Dela Cruz et 
                           al., 1987).

                  9.4.12.3 Others

                           No data available.

           9.4.13 Allergic reactions 

                  Intolerance to iodised X-ray contrast media may cause 
                  reactions consisting of fever, chills, malaise, nausea 
                  and vomiting, skin rash, diarrhoea and even 
                  hypotension. These may be classified as idiosyncratic. 
                  In patients with a history of idiosyncratic reaction 
                  premedication with corticoids and histamines is 

                  indicated or non-ionic contrast reagents should be 
                  used,(Soyer & Levesque, 1990). After interleukin-2 
                  administration an increased incidence of 
                  hypersensitivity to iodine was observed, (Zukiwski et 
                  al., 1990).
                  
                  Hypersensitivity reactions were reported in 14 cases, 
                  secondary to the application of iodine-alcohol 
                  solutions to the skin. Symptoms reported were fever 
                  and generalised skin eruption of varying types. 
                  Despite the wide use of tincture of iodine the 
                  incidence of systemic reactions is low (Seymour, 
                  1937).

           9.4.14 Other clinical effects 

                  No data available.

           9.4.15 Special risks 

                   Pregnancy
                  
                  Maternal ingestion of iodine containing substances 
                  during pregnancy can cause (transient) primary 
                  hypothyroidism in the newborn, (Coakley et al., 1989).
                  
                  Exposure to iodine and radioactive iodine in pregnancy 
                  may lead to permanent hypothyroidism or goitre in the 
                  newborn. Such goitres may become very large and even 
                  create problems during delivery or mechanical 
                  compression during early postnatal life (Bouillon, 
                  1988).
                  
                   Breast feeding
                  
                  Similar warnings to those given for pregnancy against 
                  the use of iodine or iodine-containing drugs applies 
                  during lactation since iodine is actively secreted in 
                  milk, (Bouillon, 1988).
                                   
       9.5 Other

           No data available.

       9.6 Summary

           Not relevant

    10. MANAGEMENT

        10.1 General principles 

             Do not induce vomiting nor do gastric lavage.
             
             Treatment is symptomatic.
             
             In symptomatic patients, early endoscopy is indicated in 
             order to provide an early evaluation of the corrosive 
             lesions in the oesophagus and the stomach.

        10.2 Relevant laboratory analyses 

             10.2.1 Sample collection

                    Blood and urine samples should be collected.

             10.2.2 Biomedical analysis

                    The urine may reveal albumin, casts, red blood 
                    cells, and leucocytes.
                    
                    Evidence of haemolysis may be found.
                    
                    Metabolic acidosis (lactic acidemia) has been 
                    reported.

             10.2.3 Toxicological analysis

                    Plasma iodine levels are not clinically useful but 
                    may aid in diagnosis.
                    
                    Analysis of iodine in blood and urine may be done by 
                    colorimetry or gas chromatography.

             10.2.4 Other investigations

        10.3 Life supportive procedures and symptomatic/specific 
             treatment 

             Support cardiovascular and respiratory functions. Oxygen 
             with assisted ventilation may be needed.
             
             Observe for gastrointestinal lesions, particularly rupture 
             of the oesophagus or stomach which may result in 
             mediastinitis or peritonitis, respectively.
             
             Be prepared to treat an anaphylactic type reaction.
             
             Monitor fluid and electrolyte carefully.
             
        10.4 Decontamination 

             Oral exposure
             
             Do not induce vomiting nor do gastric lavage.

        10.5 Elimination

             Dialysis is reported to be effective in an early phase, 
             (Peitsch & Meakins, 1976).
             
             Saline diuresis is useful if renal function is adequate, 
             (Dreisbach & Robertson, 1987).

        10.6 Antidote treatment
             
             10.6.1 Adults

                    No antidote available.

             10.6.2 Children

                    No antidote available.

        10.7 Management discussion

             Not relevant.

    11. ILLUSTRATIVE CASES

        11.1 Case reports from literature 

             Case 1
             
             Continuous irrigation with povidone-iodine in a 34-month-
             old patient with mediastinitis was associated with iodine 
             toxicity, resulting in fatalities, (Glick et al., 1985). It 
             is suggested that povidone-iodine continuous irrigation of 
             the mediastinum be a contraindication.
             
             Case 2
             
             A 63-year-old woman with a suppurative mediastinitis, 
             treated with continuous Polyvinyl-pyrrolidone-iodine (PI) 
             irrigation developed an acute oliguric renal failure due to 
             systemic toxicity of PI. The withdrawal of PI was followed 
             by a complete improvement of renal function, (Campistol et 
             al., 1988).
             
             Case 3
             
             Two patients with leg ulcers got worse after the 
             application of a compound mixture of sugar and povidone 
             iodine (sugar/PI compound). Patch-tests showed positive 
             reactions to 10% povidone-iodine in water and 5% potassium 
             iodide in water with no response to sugar. They were also 
             tested with sugar/PI compound containing 3% povidone 
             iodine, resulting in another positive reaction. They 
             improved after the application of sugar/PI compound was 
             discontinued, (Kudo et al., 1988).
             
             Case 4
             
             A 34-year-old male with burns covering 80% BSA and a 22-
             year-old female with a 45% BSA burn, showed hyperthyroidism 
             induced by topical treatment with 1% povidone-iodine. After 

             topical treatment with povidone-iodine was discontinued 
             circulating thyroid hormones returned to normal values 
             within weeks (Rath and Meissl,1988).
             
             Case 5
             
             Fifteen episodes of infection due to Pseudomonas 
             aeruginosa, including peritonitis and other site 
             infections, occurred in nine patients receiving continuous 
             ambulatory peritoneal dialysis over a 27 month period. 
             Occurrence of P. aeruginosa infection was significantly 
             associated with use of povidone-iodine solution to cleanse 
             the catheter site. Local irritation and alteration in skin 
             flora caused by antiseptic solution or low-level 
             contamination of povidone-iodine solution are potential 
             mechanisms of infection (Goetz and Muder, 1989)
             
             Case 6
             
             Vaginal douching with polyvinyl pyrrolidone iodine (PVP-I) 
             during pregnancy resulted in maternal iodine overload and 
             increased the iodine content of amniotic fluid. The 
             possible effect of this therapy was evaluated on the 
             thyroid of the fetus by investigating 62 women with a mean 
             duration of amenorrhoea of 20 weeks who solicited 
             controlled abortion. Nineteen of them douched daily with 
             PVP-I for 2 consecutive days before abortion (treated 
             group). The other 43 women were not treated (control 
             group). In both groups the iodine content was determined in 
             the foetal thyroid and in amniotic fluid and maternal urine 
             at the time of abortion. In addition, in the treated group 
             the concentrations of iodine were also determined in 
             amniotic fluid and urine before therapy and in urine after 
             4 days of therapy. There were no differences in the 
             concentrations of iodine in urine and amniotic fluid in the 
             control group and in the treated group before therapy. 
             Iodine content increased more rapidly in the treated group 
             (from 1 to 7.7 micrograms) than in the control group (from 
             1 to 2.5 micrograms) P less than 0.05  (Mahillon et al., 
             1989).
             
             Case 7
             
             Approximately 570,000 newborns were tested for congenital 
             hypothyroidism between May 1977 and December 1986. One 
             hundred and sixty cases of primary hypothyroidism, were 
             later found to be transient. 14 out of the transient cases 
             were due to excessive intake of iodine. In two, this was 
             due to maternal ingestion of iodide during pregnancy and in 
             12 the babies received large amounts of topical iodine 
             antiseptic. Two cases were caused by maternal anti-thyroid 
             antibodies and in eight instances the cause was unknown. 
             The large number of cases due to topical application of 
             iodine antiseptic emphasizes the need for caution when 
             using this substance in neonates (Coakely et al., 1989).

        11.2 Internally extracted data on cases

             No data available.

        11.3 Internal cases

             To be completed by the Centre using local data

    12. ADDITIONAL INFORMATION

        12.1 Availability of antidotes

             No data available.

        12.2 Specific preventive measures

             Do not use iodine as an antiseptic in neonates.

        12.3 Other
             
    13. REFERENCES

        Alvarez E (1979) Neutropenia in a burn patient being treated 
        topically with povidone-iodine foam.  Plastic Reconstr Surg, 
        63: 839-840.
        
        Barker WH & Wood WB Jr (1940) Severe febrile iodism during the 
        treatment of hyperthyroidism. Jama, 114: 1029-1038.
        
        Bell GO & Hall J (1960)  Hyperthyroidism & pregnancy.  Med Clin 
        North Am, 44: 363.
        
        Block JH, Roche EB, Soine TO et al. (1974)  Inorganic medicinal 
        and pharmaceutical chemistry. Lea & Febiger, Philadelphia,  
        pp 332-324.
        
        Bouillon R (1988) Thyroid and antithyroid drugs In: Dukes MNG. 
        Meyler's side effects of drugs, 11th Ed., Elsevier, Amsterdam, 
        Netherlands.
        
        Boyages SC, Bloot AM, Maberly GF, Eastman CJ, Li M, Qian QD, Liu 
        DR, van der Gaag RD, & Drexhage HA (1989)  Thyroid autoimmunity 
        in endemic goitre caused by excessive iodine intake. Clin 
        Endocrinol (Oxf), 31: 453-465.
        
        Cacoub P, Deray G, Baumelou A, Achour A, Eugene M, Launay O, & 
        Jacobs C (1987) Nephrotoxicite' des produits de contrast iodes. 
        Ann Med Intern (Paris), 138:635-40.
        
        Campistol JM, Abad C, Nogu S,  & Bert A (1988)  Acute renal 
        failure in a patient treated by continuous povidone-iodine 
        mediastinal irrigation. Journal of Cardiovascular Surgery, 
        29(4): 410-412.
        
        Cevallos JL, Hagen GA, Maloof F,  & Chapman EM (1974) Low-dosage 
        131-I therapy of thyrotoxicosis (diffuse goitres).  A five-year 
        follow-up study.  N Eng J, 290: 141-143.
        
        Chabrolle JP & Rossier A (1978)  Goitre and hypothyroidism in 
        the newborn after cutaneous absorption of iodine. Arch Dis 
        Child, 53: 495.
        
        Clayton GD & Clayton FE eds. (1981-1982). Patty's industrial 
        hygiene and toxicology. volumes 2A, 2B, 2C: Toxicology, 3rd ed. 
        New York: John Wiley Sons, p 2974.
        
        Coakley JC, Francis I, Gold H, Mathur K, & Connethy JF (1989) 
        Transient primary hypothyroidism in the newborn. Experience of 
        the victorian neonatal thyroid screening programme. Australian 
        Paediatric Journal, 25 (1): 25-30.
        
        Cosman BC, Schullinger JN, Bell JJ & Reagan JA (1988)  
        Hypothyroidism caused by topical povidone-iodine in a newborn 
        with omphalocele J. Ped Surg, 23: 356-358.
        
        Crocker D & Vandam LD (1963)  Untoward reactions to 
        radiodiagnostic contrast media. Clin Pharmacol Ther, 4: 654.
        
        Danziger Y, Pertzelan A & Mimouni M (1987)  Transient congenital 
        hypothyroidism after topical iodine in pregnancy and lactation. 
        Arch Dis Child, 62: 295-296.
        
        D'Auria J, Lipson S, & Garfield JM (1990)  Fatal iodine toxicity 
        following surgical debridement of a hip wound; case report. J 
        Trauma, 30: 353-355.
        
        Dela Cruz F, Brown DH, Leiken JB et al (1987) Iodine absorption 
        after topical administration. West J Med, 146: 43-45.
        
        Dreisback RH & Robertson WO (1987)  Iodine, iodoform, 
        iodochlorohydroxyquin, chiniofon & iodides. Handbook of 
        poisoning: prevention, diagnosis & treatment, 12th Ed. Appleton 
        & Lange, Los Altos, California, pp 362-364.
        
        Drinka PJ & Nolten WE (1988)  Effects of iodinated glycerol on 
        thyroid function studies in elderly nursing home residents. J Am 
        Geriatr Soc, 30: 353-355.
        
        Dukes MNG (1988)  Meyler's side effects of drugs 11th ed. 
        Amsterdam , Elsevier.
        
        Dyck RF, Bear RA, Goldstein MB, & Halperin ML (1979) 
        Iodine/iodide toxic reaction and case report with emphasis on 
        the nature of the metabolic acidosis. Can Med Assoc J, 120: 704-
        706.
        
        Ehrich WE & Seifter J (1949) Thrombotic thrombocytopenic purpura 
        caused by iodine. Arch Pathol, 47: 446-449.
        
        Finkelstein R & Jacobi M (1937)  Fatal iodine poisoning: a 
        clinical pathologic and experimental study. Ann Intern Med, 
        10: 1283-1296.
        
        Fleeger CA ed. (1993) USAN 1994: USAN and the USP dictionary of 
        drug names. Rockville, MD, United States Pharmacopeial 
        Convention, Inc., p 346.
        
        Fradkin J (1983)  Iodine-induced thyrotoxicosis. Medicine, 
        62: 1.
        
        Galima MP, Arnet NC, & Eimmorn A (1962)  Iodides during 
        Pregnancy and apperent cause of death.  New eng journal of med. 
        267;1124-1127.
        
        Geisthoevel W (1984) Hyperthyreose nach jodhaltigen 
        augentropfen. Dtsch Med Wochenschr, 109: 1304-5.
        
        Gershenfeld L (1968)  Iodine. Disinfection, sterilization and 
        preservation. Lawrence CA & Block SS eds. Philadelphia, Lea & 
        Febiger, p 329.
        
        Gilman AG, Rall TW, Nies AS & Taylor P eds.(1990) Goodman and 
        Gilman's the pharmacological basis of therapeutics, 8th ed. New 
        York, Pergamon Press, pp 972
        
        Glick PL, Guglielmo J, Tranbaugh RF, & Turley K (1985) Iodine 
        toxicity in a patient treated by continuous povidine-iodine 
        mediastinal irrigation. Ann Thoracic Surg, 39: 478-480.
        
        Goetz A & Muder RR (1989)  Pseudomonas aeruginosa infections 
        associated with use of povidine-iodine in patients receiving 
        continuous ambulatory peritoneal dialysis. Infection Control & 
        Hospital Epidemiology, 10(10): 447-450.
        
        Gommolin IH (1987) Iodated glycerol-induced hypothyroidism. Drug 
        Intell Clin Pharm, 21: 726-727.
        
        Gosselin RE, Smith RP, & Hodge HC (1984) Iodine: Clinical 
        toxicology of commercial products. Fifth Edition, Baltimore, 
        Williams and Wilkins.
        
        Grant WM (1974)  Toxicology of the eye, 2nd ed. Springfield, 
        Illinois, Charles C. Thomas, p 587.
        
        Haddad LM & Winchester JF  eds. (1983) Clinical management of 
        poisoning and drug overdose. Philadelphia, Saunders.
        
        Harbison RD (1980) Teratogens in: Doull J, Klaassen CD,  & Amdur 
        MO, Cassarett and doull's toxicology. The basic science of 
        poisons. Second Edition. Macmillan Publishing Co, Inc., New 
        York, p 70.
        
        Harvey SC (1985)  Antiseptics and disinfectants; fungicides, 
        ectoparasificides. In: Gilman AG, Goodman LS, Rall TW & Murad F 
        eds. (1985) Goodman & Gilman's  the pharmacological basis of 
        therapeutics. 7th ed. New York, Macmillan Publishing Company, 
        pp 959-979.
        
        Haynes Jr (1990) Thyroid and antithyroid drugs. In Gilman AG, 
        Rall TW, Nies AS & Taylor P eds.(1990) Goodman and Gilman's the 
        pharmacological basis of therapeutics, 8th ed. New York, 
        Pergamon Press, pp 1361-1383.
        
        Hunt JL, Sato R, Heck EL,  & Baxter CR  (1980)  A critical 
        evaluation of povidine-iodine absorption in thermally injured 
        patients. J Trauma, 20: 127-129.
        
        International Labour Office (1971) Encyclopedia of occupational 
        health and safety. Volumes 1 and 11. New York: McGraw-Hill Book 
        Co., p 740.
        
        Jones LM et al (1977) Veterinary Pharmacology & Therapeutics 4th 
        Edition. Ames:Iowa State Univesity Press, p 802.
        
        Klein I & Levey GS (1983)  Iodide excess and thyroid function. 
        Ann Intern Med, 98: 406-407.
        
        Kobberling J, Hintze G & Becker HD (1985)  Iodine-induced 
        thyrotoxicosis -a case for subtotal thyroidectomy in severely 
        ill patients. Klin Wochenschr, 63: 1-7.
        
        Kudo H, Takahashi K, Suzuki Y, Tanaka T, Miyachi Y, & Immamira S 
        (1988) Contact dermatitis from a compound mixture of sugar, and 
        povidone-iodine Contact dermatitis, 18 (3): 155-157.
        
        L'Allemand D, Grueters A, Beyer P,  & Weber B (1987) Iodine in 
        contrast agents and skin disinfectants is the major cause for 
        hypothyroidism in premature infants during intensive care. Horm 
        Res 28:42-9.
        
        Lavelle KJ, Doedens DJ, Kleit SA &  Forney RB (1975) Iodine 
        absorption in burn patients treated topically with povidine-
        iodine. Clin Pharmacol Ther 17:355-362.
        
        Luckhardt AB, Koch FC, Schroeder WF, & Weiland AH (1920) The 
        physiological action of fumes of iodine. J Pharmacol Exp Ther 
        15:1-21.
        
        Mackenroth T (1990) Bei thyreotoxischer krise sofortige 
        volumentherapie. Jodhaltige Medikamente als Hanptverursacher. 
        Fortschr Med 108: 14-6
        
        Mahillon I, Peers W, Bourdoux P, Ermans AM, & Delange F (1989) 
        Effect of vaginal douching with povidone-iodine during early 
        pregnancy on the iodine supply to mother and foetus. Biology of 
        the Neonate 56(4): 210-217.
        
        Martino E, Aghini-Lombardi F, Mariotti S, Bartalena L, Braverman 
        L, & Pinchera A (1987) Amiodarone: a common source of iodine-
        induced thyrotoxicosis. Horm Res 26:158-71.
        
        McEvoy GK ed. (1990) American hospital formulary service, drug 
        information, Bethesda, American Society of Hospital Pharmacists.
        
        National Fire Protection Association (1978) Fire protection 
        guide on hazardous materials. 7th ed. Boston, Mass, National 
        Fire Protection Association, 491M-48.
        
        National Research Council (1980) Drinking water and health, 
        volume 2. Washington DC, National Academy Press,  p 65.
        
        Ohmori S et al (1981). Radioactivation analysis of hair. A means 
        of biological monitoring of the environment. J. Radioanal Chem 
        63(2), 269.
        
        Okano M (1989) Irritant contact dermatitis caused by povidone-
        iodine (letter). Journal of the American Academy of Dermatology, 
        20(5Pt1):860.
        
        Osol A ed. (1980) Remington's pharmaceutical sciences, 15th ed. 
        Easton, Pennslyvannia: Mack Publishing Co, p 1092.
        
        Parmalee AH. Allen E, Stein IF et al: (1940) Three cases of 
        congenital goiter. Am J Obstet Gynecol 40:145-147.
        
        Peitsch J & Meakins JL (1976) Complications of povidine-iodine 
        absorption in topically treated burn patients. Lancet, 
        1:280-281.
        
        Prager EM & Gardner RE (1979) Iotrogenic hypothyroidism from 
        topical iodine-containing medications. West J Med, 130:553-555.
        
        Pyati SP, Ramamurthy R, Krauss MT, & Pildes RS (1977) Absorption 
        of iodine in the neonate following topical use of povidine-
        iodine. J Pediatr, 91:825.
        
        Rath T  & Meissl G (1988) Induction of hyperthyroidism in burn 
        patients treated topically with povidine-iodine. Burns, 
        including Thermal injury, 14(4): 320-322.
        
        Regouby Y, Vignancour P, Delomez G, & Lavarenne J (1985) 
        Intoxication a' l'iode due a l'amiodarune. Presse Med, 
        14:1928-9.
        
        Reynolds JEF ed. (1989) Martindale, the extra pharmacopoeia, 
        29th ed. London, The Pharmaceutical Press, pp 1184-1186.
        
        Reynolds JEF ed. (1993) Martindale, the extra pharmacopoeia, 
        30th ed. London, The Pharmaceutical Press. pp 970-972.
        
        Schoenberger W & Grim W (1982) Transiente hypothyreosen durch 
        jodhaltige desinfizientien bei neugeborenen. Dtsch Med 
        Wochenschr 107:1222-7.
        
        Seymour WB (1937) Poisoning from cutaneous application of 
        iodine. Arch Intern Med 59: 952-966.
        
        Shepard TH (1980) Catalog of teratogenic agents 3rd ed. 
        Baltimore MD. Johns Hopkins University Press, p 584.
        
        Shilo S & Hirsch HJ (1990) Iodine induced hyperthyroidism in a 
        patient with a normal thyroid gland. Postgr Med J 62:661-2.
        
        Sittig M (1981) Handbook of toxic and hazardous chemicals. Park 
        Ridge, New Jersey, USA, Noyes Publications,  p 388-389.
        
        Smerdely P, Lim A, Boyages SC, Waite K, Wu D, Roberts V, Leslie 
        G, John E, & Eastman CJ (1989) Topical iodine containing 
        antisptics and neonatal hypothyrodism in very low-birthweight 
        infants. Lancet,  2 (8664): 661-4.
        
        Soyer P & Levesque M (1990) Prevention des accidents 
        d'intolerance aux produits de contraste iodes. Presse Med, 
        19:562-5.
        
        Steidle B (1989) Iodine-induced hypethyroidism after contrast 
        media; animal experimental and clinical studies. Fortschr Geb 
        Rontgenstr Nuclearmed Erganzungsband, 128:6-14.
        
        Vorherr H, Vorrherr UF, Mehta P Ulrich JR, & Messer RH (1989) 
        Vaginal absorption of povidine-iodine. Jama 244:2628-2629.
        
        Windholz M ed. (1983)  The Merck Index: an encyclopedia of 
        chemicals, drugs, and biologicals, 10th ed. Rahway, New Jersey, 
        Merck and Co., Inc.
        
        Wolff J & Chaikoff IL (1984) Plasma inorganic iodide as a 
        homeostatic regulator of thyroid function.  J Biol Chem, 
        174: 555-564.
        
        Zukiwski AA, David CL, Coan J, Wallace S, Gutterman JU, & 
        Mavligit GM.(1990) Increased incidence of hypesensitivity to 
        iodine-containing radiographic contrast media after interleukin-
        2 administration. Cancer, 65:1521-4.
        
    14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE 
        ADDRESS(ES) 
        
        Authors        Dr  Ossy J. Kasilo
                       Drug and Toxicology Information Service
                       Department of Pharmacy
        
                       Dr  C.F.B. Nhachi
                       Department of Clinical Pharmacology
                       and Toxicology, University of Zimbabwe
                       Medical School
                       P.O. Box A178 Avondale
                       Harare
                       Zimbabwe
        
        Tel            263-4-790233 or 791631 ext. 117/172
        Fax            263-4-732828
        Telex          26580 UNIV ZW
        
        Date           February 1990
        
        Updates        June 1990,  November 1990
        
        Reviewer       Professor  A.N.P. van Heijst
                       Baarnseweg 42A
                       3735 MJ Bosch en Duin
                       Netherlands
        
        Tel            030-287178
        
        Peer review    Drs Hussein, Kasilo, Van Heijst, Ms Kirby
                       Adelaide, Australia, April 1991.







Iodine (PIM 280)



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    See Also:
       Toxicological Abbreviations
       Iodine (ICSC)
       Iodine (WHO Food Additives Series 24)
       IODINE (JECFA Evaluation)