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Toxicological information

Carcinogenicity

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Description of key information

It was therefore concluded that long-term treatment of iodide per se does not result in thyroid tumor induction in rats.  In the salivary gland, iodide was suggested to have carcinogenic potential via an epigenetic mechanism, only active at a high dose 1000 ppm in drinking water.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Dose descriptor:
LOAEL
100 mg/kg bw/day

Justification for classification or non-classification

Iodide does not induce thyroid tumors in rats. In the salivary gland, KI was suggested to have carcinogenic potential via an epigenetic mechanism, at a high dose. However there is still no data about the possibility of the carcinogenic potential deduction from rat to human. Additionally the potential is only existed at high dose to rat. Therefore, the iodide dose neither meet the carcinogenicity criteria under the Regulation (EC) No. 1272/2008 nor Directive 67/548/EEC.

Additional information

A chronic toxicity and carcinogenicity study, in which male and female F344/DuCrj rats were administrated iodide (KI) in the drinking water at concentrations of 0, 10, 100 or 1000 ppm for 104 weeks was conducted. In the test, neither focal hyperplasias, adenomas nor carcinomas derived from the follicular epithelium were increased, despite the fact that iodide was administered for 2 yr. It was therefore concluded that long-term treatment of iodide per se does not result in thyroid tumor induction in rats. In contrast, SCCs were observed in the submandibular gland in the 1000 ppm groups of both sexes, along with focal acinar atrophy and/or ductular proliferation, frequently accompanied by squamous metaplasia. Based on the fact that the cell proliferation of these proliferating ductules was higher in cases with metaplasia, and the evidence of a morphological continuum from meta-plasias to squamous cell carcinomas, a histogenetic relationship is suspected, which was also described in previous investigation (Takegawa et al., 1998).

Based on these findings, it suggests that excess iodide has a thyroid tumor-promoting effect, but iodide per se does not induce thyroid tumors in rats. In the salivary gland, iodide was suggested to have carcinogenic potential via an epigenetic mechanism, only active at a high dose (1000 ppm in drinking water).

The default value of volume of drinking water for rat is well accepted of 10 ml/100g bw·day, and the average body weight for rat is 250g. Based on these the LOAEL for salivary glands for carcinogenicity is proposed to be 100 mg/kg bw·day of iodide by drinking water.


Carcinogenicity: via oral route (target organ): digestive: salivary glands