Iodine

Neurotoxicity

Description of key information

There is an extensive amount of publically available literature on iodine, including human data that indicates that the primary target organ in mammals is the thyroid gland. Neurological effects that have occurred due to thyroid gland disorders are well characterised and have been documented in clinical literature as reviewed by the Agency for Toxic Substance and Disease Registry (ATSDR, 2004). The USEPA (2006) toxicology review of iodine and iodophor complexes also cites the references used in the ATSDR review and has adopted similar conclusions. Therefore, a weight of evidence approach for not requiring specific neurotoxicity data is appropriate as these reviews have cited a variety of relevant publications to support the conclusions below.

The ATSDR noted that oral exposure to excess stable iodine has been shown to produce subclinical hypothyroidism that make take the form of hypothyroidism in sensitive populations. The ATSDR further documented that from these iodine induced forms of hypothyroidism, that the foetus or newborn infant has the greatest potential for producing neurological effects. This is because thyroid hormones are essential to the development of the neuromuscular system and brain. Exposure to excess stable iodine can also produce hyperthyroidism in sensitive individuals including those who are initially iodine deficient, those who have thyroid disease, those who have been previously treated with antithyroid drugs and those who have developed thyrotoxicosis from amiodarone or interferon alpha treatments. The ATSDR states that patients that have developed thyrotoxicosis can experience neuromuscular disorders, such as myopathy, periodic paralysis, myasthenia gravis, peripheral neuropathy, tremor, and chorea. However, the ATSDR concluded that these are not likely to occur in iodine induced hyperthyroidism, except in sensitive groups, already at risk for neurological problems.

In terms of dermal exposure, the ATSDR notes that exposure to excess iodine may produce mild transient hypothyroidism and hyperthyroidism that could result in neurological manifestations of thyroid gland dysfunction including impairments in neurological development and myopathies. However, based on the mild effects that have been observed in association with dermal exposures, severe neurological effects are considered to be unlikely. Any potential neurological effects associated with iodine exposure are secondary to effects on the thyroid gland. Furthermore, potential neurological effects associated with iodine will most likely be due to iodine deficiency. Iodine is an essential component of the thyroid hormones T3 and T4 which are necessary for neuronal development, as well as growth and regulation of metabolic rate. Without dietary iodine intake, the thyroid gland will not function optimally, and signs of thyroid insufficiency will affect necessary physiological processes. This is the basis for measures used to ensure adequate iodine ingestion such as iodised salt.

While both insufficiencies and excessive intake can adversely affect human health, inadequate iodine intake is a major problem in the world today, affecting approximately one sixth of the world’s population. Iodine deficiency disorders are related to the degree of iodine deficiency. Neurological deficits or minor neuropsychological impairments have been described in European countries characterised by mild to moderate iodine deficiency (WHO, 2009). The same conclusion was derived by WHO (2020), in their latest background document for the development of guidelines for drinking-water quality for iodine in drinking-water. In conclusion, as the Derived No Effect Levels (DNEL) are derived from effects on the thyroid as the most sensitive target organ, the human health exposure and risk characterisation assessment will also take into account potential neurological effects. Iodine is also an essential component of the thyroid hormones T3 and T4 which are necessary for neuronal development, and a deficiency of iodine can result in neurological deficits. Therefore, a specific study that investigates neurotoxic effects is not considered to be necessary.

References:

- ATSDR, 2004: Toxicological Profile for Iodine. U.S. Department of Health and Human Services.

- USEPA, 2006: Iodine and Iodophor Complexes, Revised Toxicology Chapter in Support of Issuance of the Reregistration Eligibility Document (RED) Document.

- WHO Concise International Chemical Assessment Document (CICADS) 72 - Iodine and Inorganic Iodides: Human Health Aspects (2009).

- WHO, 2020: Iodin in drinking-water: Background document for development of WHO guidelines for drinking water quality.

Additional information

There is an extensive amount of publically available literature on iodine, including human data that indicates that the primary target organ in mammals is the thyroid gland. Neurological effects that have occurred due to thyroid gland disorders are well characterised and have been documented in clinical literature. In conclusion, as the Derived No Effect Levels (DNEL) are derived from effects on the thyroid as the most sensitive target organ, the human health exposure and risk characterisation assessment will also take into account potential neurological effects. Iodine is also an essential component of the thyroid hormones T3 and T4 which are necessary for neuronal development, and a deficiency of iodine can result in neurological deficits. Therefore, a specific study that investigates neurotoxic effects is not considered to be necessary.

Reference:

- ATSDR, 2004: Toxicological Profile for Iodine. U.S. Department of Health and Human Services.

- WHO, 2020: Iodin in drinking water, Background document for development of WHO guidelines for drinking-water quality.

- USEPA, 2006: Iodine and Iodophor Complexes, Revised Toxicology Chapter in Support of Issuance of the Reregistration Eligibility Document (RED) Document.

- WHO Concise International Chemical Assessment Document (CICADS) 72 - Iodine and Inorganic Iodides: Human Health Aspects (2009).

- WHO, 2020: Iodine in drinking-water: Background document for development of WHO guidelines for drinking water quality.

Justification for classification or non-classification

As iodine is classified for specific target organ toxicity (STOT) (repeated exposure) Category 1 with the thyroid as the primary target organ, a suitable classification has been assigned which considers the above information. Further specific neurotoxicity data would not alter the STOT Category 1 classification or the proposed risk mitigation measures.