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Description of key information

TDI of iodide is  0.01 mg/kg body weight.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
0.01 mg/kg bw/day

Additional information

The most likely route for human exposure is via digestion, so the dermal and inhalation route are irrelevant in the repeated toxicity assessment.

Boyages et al. (1989) compared thyroid status in groups of children 7–15 years of age who 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). Urinary iodine concentrations were 1236 μg/g creatinine in the high-iodine group and 428 μg/g creatinine in the low-iodine group. Although the subjects were all euthyroid, with normal values for serum thyroid hormones and TSH concentrations, TSH concentrations were significantly higher (P < 0.05) in the high-iodine group. The high-iodine group had a 65% prevalence of goitre and a 15% prevalence of Grade 2 goitre compared with 15% for goitre and 0% for Grade 2 goitre in the low-iodine group. To transform the measured urinary iodine levels into estimates of iodine intakes, steadystate baseline dietary intakes of iodide were assumed to be equivalent to the reported 24-h urinary iodine excretion rates

Assuming a body weight of 40 kg and lean body mass of 85% of body weight, the urinary iodine/creatinine ratios reported by Boyages et al. (1989) can be converted to approximate equivalent intake rates of 1150 μg/day (0.029 mg/kg body weight per day) and 400 μg/day (0.01 mg/kg body weight per day) for the high- and low-iodine groups, respectively. Thus, the NOAEL for this study is considered to be 0.01 mg/kg body weight per day.

Supporting studies indicate that the NOAEL from the Boyages et al. (1989) study would be applicable for both acute and chronic-duration exposure of elderly adults, who may represent another sensitive subpopulation (Chow et al., 1991; Szabolcs et al., 1997). In the Chow et al. (1991) study, 30 healthy 60 to 75-year-old females from,, received daily doses of 500 μg iodine per day for 14 or 28 days. Serum concentrations of free T4 were significantly decreased, and serum TSH concentrations were significantly elevated. On average, the magnitude of the changes did not produce clinically significant depression in thyroid hormone levels; however, five subjects had serum TSH concentrations that exceeded 5 mU/l. The pre-existing dietary iodine intake was approximately 72-100 μg/day, based on urinary iodide measurements. Therefore, the total iodide intake was approximately 600 μg/day (0.0087 mg/kg body weight per day, based on a mean weight of 69 kg for women 19–64 years of age in the British National Diet and Nutrition Survey; British Nutrition Foundation, 2004).Szabolcs et al.(1997) studied elderly nursing home residents who had received long-term exposure to iodine in one of three regions where the intakes were estimated to be approximately 117, 163, or 834 µg/day (0.0017, 0.0023, or 0.012 mg/kg body weight per day for low, moderate, or high intake, respectively). The prevalence of clinical hypothyroidism was 0.8%, 1.5%, and 7.6% in the low-, moderate-, and high-iodine groups, respectively. Serum TSH concentrations were elevated as free T4 levels were reduced (P = 0.006).

In a study by Paul et al. (1988), healthy euthyroid adults (nine males, nine females) who had no history of thyroid disease or detectable antithyroid antibodies received daily oral doses of 250, 500, or 1500 μg iodine (as sodium iodide) per day for 14 days. Based on 24-h urinary excretion of iodide prior to the iodide supplement, the background iodine intake was estimated to be approximately 200 μg/day; thus, the total iodide intake was approximately 450, 700, or 1700 μg/day (approximately 0.0064, 0.01, or 0.024 mg/kg body weight per day, assuming a 70-kg body weight). Subjects who received 1700 μg/day (0.024 mg/kg body weight per day) had significantly depressed (5–10%) serum concentrations of total T4, free T4, and total T3 compared with pretreatment levels, and serum TSH concentrations were significantly elevated (47%) compared with pretreatment values. Hormone levels were within the normal range during treatment. In this same study, nine females received daily doses of 250 or 500 μg iodine per day for 14 days (total intake was approximately 450 or 700 μg/day; 0.0064 or 0.010 mg/kg body weight per day), and there were no significant changes in serum hormone concentrations.

In a comparable quality study by Gardner et al. (1988), 10 healthy adult euthyroid males received daily oral doses of 500, 1500, or 4500 μg iodine (as sodium iodide) per day for 14 days. Based on 24-h urinary excretion of iodide of 256–319 μg/day prior to the iodide supplement, the total estimated intakes were 800, 1800, or 4800 μg/day, or approximately 0.011, 0.026, or 0.069 mg/kg body weight per day. In this study, there were no effects on serum thyroid hormone or TSH concentrations at the 800 μg/day intake (0.011 mg/kg body weight per day); however, intakes of 1800 or 4800 μg iodine per day (0.026 or 0.069 mg/kg body weight per day) produced small (10%), but significant, transient decreases in serum total T4 and free T4 concentrations and an increase (48%) in serum TSH concentration, relative to the pretreatment values.

From the Boyages et al. (1989) study, supported by the studies of Gardner et al. (1988), Paul et al. (1988), and others, a TDI of 0.01 mg/kg body weight, based upon reversible subclinical hypothyroidism, can be established by dividing the NOAEL of 0.01 mg/kg body weight per day by an uncertainty factor of 1.

Potassium iodide (KI) was fed to male and female rats before and during breeding (Vorhees, C.V., R.E. Butcher, and R.L. Brunner, 1984), to females only during gestation and lactation, and to their offspring after weaning (day 21 after birth) through to day 90, at levels of 0, 0.025, 0.05 or 0.1% (w/w) of the diet.In rats killed on day 90 after birth KI reduced brain and body weight at a dose of 0.1% of the diet, and reduced body but not brain weight at a dose of 0.05% of the diet. No significant effect was found on absolute or relative thyroid weight at 90 days of age. Several additional behavioural effects were observed in the low-dose KI group, but because these effects were not dose-dependent, they were not regarded as reliable. 5-Azacytidine produced evidence of substantially greater developmental toxicity than KI. It was concluded that KI produced evidence of developmental toxicity consistent with a picture of impaired thyroid function. The inclusion of tests of functional development added useful evidence to the overall picture of KI developmental toxicity. No significant effect was found on absolute or relative thyroid weight at 90 days of age. Several additional behavioural effects were observed in the low-dose KI group, but because these effects were not dose-dependent, they were not regarded as reliable. 5-Azacytidine produced evidence of substantially greater developmental toxicity than KI. It was concluded that KI produced few evidence of developmental toxicity consistent with a picture of impaired thyroid function. The inclusion of tests of functional development added useful evidence to the overall picture of KI developmental toxicity.

Since the TDI has been derived by WHO, this value will be used as key value in this section.


Repeated dose toxicity: via oral route - systemic effects (target organ) glandular: thyroids

Justification for classification or non-classification

Evidently iodide need to be classified as specific target organ toxicity — repeated exposure, category 1 underthe Regulation (EC) No. 1272/2008, and T; R48/25 under the Directive 67/548/EEC.