Iodine

Endpoint summary

Description of key information

Hypothyroidism in healthy human (sensitive subpopulations):

Boyages et al. 1989 and Li et al 1987 compared the thyroid status in two groups of children (aged 7-15 years). The children resided in two areas of China where drinking water iodide concentrations were either 462.5 μg/L (n=120) or 54 μg/L (N=51) (Boyages et al. 1989; Li et al. 1987). In the high iodine group, there was a 65% prevalence of goitre compared with 15% in the low iodine group. Also, the high iodine group contained 15% of subjects that had a grade 2 goitre, compared with 0% having a grade 2 goitre in the low iodine group. As stated above, although the subjects were all euthyroid with normal values for serum thyroid hormones and TSH concentrations, TSH concentrations were significantly higher (33%) in the high iodine group. These key epidemiological studies are used for endpoint conclusion and dose descriptor from which the chronic NOAEL in humans has been set at 0.01 mg/kg bw/day for the most sensitive sub populations (based on subclinical hypothyroidism in healthy human children). The same data has been used bythe ATSDR and WHO as the basis for setting a mimimum risk level (ATSDR) and a Tolerable Daily Intake (WHO) of 0.01 mg/kg bw/day which are values for acceptable oral chronic exposure to iodine.

In support of developing hypothyroidism in sensitive populations (children), another case report describes a 72 year old female who developed clinical and laboratory evidence of hyperthyroidism while ingesting sea-kelp (Vitalia) tablets. Six months after stopping the tablets, the symptoms and laboratory evidence of hyperthyroidism had disappeared. No evidence of pre-existing thyroid disease was found.

Allergic contact dermatitis:

A number of human case reports of possible allergic contact dermatitis of iodine (PVP-solution) and iodine are reported. Iodine (PVP-solution) was evaluated in a human study.

A report by Oiso (2006) documents a case study whereby a patient treated for a necrotic ulcer of the left ankle was administered an ointment containing 0.9% iodine. The patient had no history of dermatitis herpetiformis. Whilst treating the ulcer, erythema developed 6 months later. Patch testing displayed a positive reaction to the ointment on D2 (+), D3 (+) and D4 (+). Further patch testing was done with the ingredients which was positive on D2 (+++), D3 (+++) and D6 (+) which identified that the iodine component in the ointment was causing the positive reactions. In control patch tests using the ointment, all 6 tested healthy volunteers displayed negative reactions. The study author considered that absorption of iodine in this case study was over a long period of time under occlusive conditions which is likely to have promoted contact sensitisation. The author further concluded that allergic contact dermatitis from iodine is not uncommon and that as iodine containing ointments are usually applied under occlusive conditions, that dermatologists should be aware of allergic reactivity to iodine in topical ointments.

Lachapelle (2005) reported a study where 500 consecutive patients were patch tested with a 10% povidone-iodine solution that was diluted 10 times in water. Readings were made at 2 and 4 days. 14 out of 500 patients (2.8%) displayed a positive reaction. The 14 patients that tested positive were given a repeated open application test with a PVP-I solution were 2 out of 14 patients were regarded as positive. From the repeat test, it was concluded that 2 out of the 500 patients showed true allergic contact dermatitis from PVP-I (0.4%). The study concluded that substances that share both irritant and allergic properties (e.g. PVP-I) should be investigated more thoroughly to rule out false positive patch test results.

Overall, human case studies on the allergic contact dermatitis of iodine are available but with equicocal results.

Additional information

The thyroid gland is the main storage organ for iodine. It is also the target of iodine toxicity. Exposure to excess iodine can lead to hypothyroidism (with or without goitre – enlargement of the thyroid), hyperthyroidism, and changes in the incidence and types of thyroid malignancies (WHO, 2020).

The adverse effects associated with high levels of iodine intake are linked to disruption of thyroid hormone metabolism and the thyroid–pituitary axis, and the compensatory mechanisms that protect this metabolism from low or high levels of iodine intake. Previous exposures to iodine and the complex effects of pre-existing thyroid conditions also influence the effects of subsequent exposure. Members of the general population who are vulnerable to iodine toxicity include pregnant and lactating women, and neonates (WHO, 2020).