Sodium periodate

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Remarks:

The study was conducted on the read across substance, potassium iodate. Investigations on the gastric hydrolysis of the registration substance indicate a chemical reaction of periodate to iodate thereby confirming the validity of the read across.

Cross-reference

Reason / purpose for cross-reference:

other: read across: target

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

The source material is potassium Iodate and the target is sodium periodate. The analogue approach has been used due to the predicted common breakdown products specifically ionised iodine whilst the potassium ion in the source material and the sodium ion in the target material are historically established to have similar properties. Once injested, the materials are anticipated to form highly similar breakdown products with historically recognised similarities.

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

NOAEL

Effect level:

3 000 other: µg/L

Based on:

test mat.

Sex:

female

Basis for effect level:

clinical biochemistry

ophthalmological examination

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

6 000 other: µg/L

System:

endocrine system

Organ:

thyroid gland

Treatment related:

yes

Dose response relationship:

not specified

Relevant for humans:

not specified

Conclusions:

Under the conditions of the study KIO3 was found to result in lower thyroxine in serum, lipid metabolism disorder and retina dysfunction in rats. The NOAEL of KIO3 in rats was determined to be 3000 μg/L. Serum TC level was found to be a sensitive contacting biomarker of excessive iodine.

Executive summary:

The repeated dose toxicity of the test material was investigated in a study in which groups of 10 female rats were administered test material, in drinking water, over a period of 13 weeks. Animals were dosed at 3000, 6000, 12 000, 24 000, 48 000, 96 000 and 192 000 µg/L, a concurrent control group was administered with plain drinking water. At the end of the treatment period, after electroretinogram examination on selected rats, all animals were sacrificed. Haematology and clinical chemistry examinations were performed. Internal organs were weighed and examined histopathologically.

 

The levels of serum TT4, TT3 and rT3 increased with increasing doses of KIO3, while total cholesterol (TC), triglyetide (TG) in serum and white blood cell (WBC) rose significantly in animals dosed at 6000 μg/L and above (P < 0.05). In addition, the amplitude of a and b waves of ERG were significantly lower in the highest KIO3 group rats compared to the control rats (P < 0.05).

Under the conditions of the study, KIO3 was found to result in lower thyroxine in serum, lipid metabolism disorder and retina dysfunction in rats. The NOAEL of KIO3 in rats was determined to be 3000 μg/L. Serum TC level was found to be a sensitive contacting biomarker of excessive iodine.

Data source

Reference

Reference Type:

publication

Title:

The Research on the Subchronic Toxicity of Potassium Iodate in Rats

Author:

Guo, H., Xu, J., Yang, H., Hou, X., Chen, X. and Sun, X.

Year:

2005

Bibliographic source:

J Toxicol 19 (4) pp 263

Materials and methods

Principles of method if other than guideline:

Groups of 10 female rats were administered test material, in drinking water, over a period of 13 weeks. At the end of the treatment period, after electroretinogram examination on selected rats, all animals were sacrificed. Haematology and clinical chemistry examinations were performed. Internal organs were weighed and examined histopathologically.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Potassium iodate

EC Number:

231-831-9

EC Name:

Potassium iodate

Cas Number:

7758-05-6

IUPAC Name:

potassium iodate

Details on test material:

- Name of test material (as cited in study report): potassium iodate
- Source: Damao (Tianjin, China)

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiaion: Weanling
- Source: Hubei laboratory animal center (Hubei, China)
- Weight at study initiation: 50 - 60 g
- Acclimation period: 5 days

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

90 days

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

3 000 other: µg/L

Doses / concentrations 2

Dose / conc.:

6 000 other: µg/L

Doses / concentrations 3

Dose / conc.:

12 000 other: µg/L

Doses / concentrations 4

Dose / conc.:

24 000 other: µg/L

Doses / concentrations 5

Dose / conc.:

48 000 other: µg/L

Doses / concentrations 6

Dose / conc.:

96 000 other: µg/L

Doses / concentrations 7

Dose / conc.:

192 000 other: µg/L

No. of animals per sex per dose:

10 females per dose

Control animals:

yes

Details on study design:

- Dose selection rationale: The dose which is 100 times the recommended nutrient intake (RNI) of iodine per adult per day was used in this experiment as the lowest dose, i.e.250 μg/kg. And the dose is 422 μg/kg if converted to KIO3. Daily water intake of rats were estimated to be 160~200 mL/kg. Thus, we can calculate that the lowest dose was 3000μg/L. Acute toxicity test which has been done in this experiment showed that the LD50 value of
KIO3 for female Wistar rats was 667 mg/kg, taking 1/20 of the LD50 value as the highest dose, i.e.33 mg/kg, and the drinking water concentration was 200 000 μg/L. Within the range of 3000~200 000 μg/L, total 7 dose groups were set up using two times the group interval.
- Rationale for animal assignment: the animals were divided into 8 groups according to their weight.

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: General conditions were observed twice daily

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

FOOD CONSUMPTION: Yes
- Time schedule for examinations: Weekly

WATER CONSUMPTION : Yes
- Time schedule for examinations: Weekly

OPHTHALMOSCOPIC EXAMINATION: Yes

BLOOD COLLECTION: Yes
The bloods were collected from caudal veins of rats to determine the haematologic parameters (clinical microscopy method). All rats were sacrificed through heart blood collection, and serum was separated for testing the serum biochemical parameters (kits, determined by semiautomatic biochemistry analyser) and thyroid hormone (radioimmunoassay).

URINALYSIS: Yes
For the determination of urine iodine level, acid digestion arsenic cerium catalytic spectrophotometric method was adopted. At the end of the 13th week, 5 rats were randomly selected from the control group and high dose groups, respectively for the ERG examination according to literature methods.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
Liver, kidney and spleen were taken and weighed, organ coefficients were calculated and the organs of each group were examined by pathological section (HE staining).

Statistics:

SPSS 12.0 software package was used for data analysis.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

During the experiment, animals of each group showed no obvious toxic reactions.

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

The weights of rats dosed at concentrations of 3000 and 6000 µg/L increased faster than animals dosed at 48 000 µg/L and above, but there was no significant difference (P > 0.05) when compared to the control group.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

The average daily food intake of rats was not affected by KIO3. The first month’s food utilisation of rats in each group also showed no obvious change trends.

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

effects observed, treatment-related

Description (incidence and severity):

Results show that high doses of KIO3 can affect the water intake of rats. The daily water intake of rats dosed at 48 000 µg/L and above decreased. Rats dosed at 48 000, 96 000 and 192 000 µg/L showed significant differences (P<0.05 or P<0.01) when compared with animals in the control group.

Ophthalmological findings:

effects observed, treatment-related

Description (incidence and severity):

- ERG: The mechanism of KIO3’s damage to retina was not clear and possibly related to its own oxidation. The appropriate amount, and high doses, of potassium iodide and KIO3 were administered to iodine deficient rats for 22 weeks. The antioxidant capacity of the normal iodine group was better than that of the 2 high iodine groups, and the total retina antioxidant capacity of rats in potassium iodide group was higher than that of the KIO3 group. Therefore, the doses and dosage forms of iodine all have significant effects on the retina antioxidant capacity of iodine deficient rats.
To test the theory that the retina toxicity of iodate is related to its interference on the metabolism of amino acid inside retina and damage of the blood retinal barrier, the ERG method was used in this study. The method found that the amplitude of a and b waves of ERG both decreased significantly in the highest dose group rats, but there was no obvious abnormity in retina pathological sections, which means high KIO3 doses can possibly damage the functions of retina at first.

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

Blood of rats in each group was tested at the end of the experiment, the leukocytes amount of rats dosed at 6000 µg/L and above increased (P<0.01) while that of other groups was within normal ranges, and there was no significant difference (P>0.05) observed for other indexes among the groups.

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

The test results of blood biochemical index at the end of the experiment suggested that KIO3 has an effect on the metabolism of sugar, lipid and protein, especially TC. The results of variance analysis showed that TC values of animals dosed at 6000 µg/L and above were all higher than that of control group, and the differences were significant (P<0.05) except for the group dosed at 96 000 µg/L. TC values tended to increase at first and then decreased, and the values of the 96 000 and 192 000 µg/L dose groups were the lowest. TP values of the two groups also declined and significant differences (P<0.05) were observed when compared to the controls. Glucose (Glu) values were also increased first and then decreased, but there was no significant difference among the groups. Other blood biochemical indexes were not significantly affected by KIO3.
- Changes of serum thyroid hormone level: The levels of serum TT4, TT3 and rT3 went up with increasing doses of KIO3 .
- ERG: The results of ERG examination suggested that the amplitude of a (18.8 ± 4.4 μv) and b (79.7 ± 18.2 μv) waves of ERG were significantly lower (P < 0.05) in rats dosed at 192 000 µg/L compared to that of other groups.

Urinalysis findings:

effects observed, treatment-related

Description (incidence and severity):

- Terminal urine iodine: The urine iodine levels of each dose group were significantly different (P < 0.01) compared with the control group. The higher the dose of KIO3, the higher the level of urine iodine.

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

The kidney/weight value of rats dosed at 192 000 µg/L and the spleen/weight value of rats dosed at 24 000, 96 000 and 192 000 µg/L increased and showed significant differences (P<0.05) compared to animals in the control group. The other organ coefficients (including ovary/weight, liver/weight and lung/weight) were not apparently affected by KIO3.

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

Pathological sections of each organ (thyroid, retina, liver, kidney, gastrointestinal, spleen, lung and ovary) were observed by microscopy, and there were no significant pathologic changes.

Histopathological findings: neoplastic:

not specified

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

3 000 other: µg/L

Based on:

test mat.

Sex:

female

Basis for effect level:

clinical biochemistry

ophthalmological examination

Target system / organ toxicity

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

6 000 other: µg/L

System:

endocrine system

Organ:

thyroid gland

Treatment related:

yes

Dose response relationship:

not specified

Relevant for humans:

not specified

Any other information on results incl. tables

Effects of KIO3 on the serum thyroid hormone level of rats

KIO3 doses of 48 000 μg/L and above can decrease the serum thyroid hormone level of rats. In the study, values of TT4, TT3 and rT3 all decreased with increasing KIO3 doses, which means that high dose of KIO3 may result in hypothyroidism of rats. There were, however, no colloid goiter of rats observed in any dose group.

 

Effects of KIO3 on the lipid metabolism of rats

Higher doses of KIO3 can increase the serum TC level. Indeed, during the study, as the KIO3 dose increased, the serum TC first increased and then decreased; serum TC was the most sensitive to high iodine. In this experiment, lipid disorder of rats was likely to be related to high iodine and hypothyroidism.

The study revealed that the TC values of groups dosed at 6000 μg/L and above were significantly higher than that of the control group. Meanwhile, the study also showed that serum TC level was more sensitive than crowd goiter rate when used as the contacting biomarker of excessive iodine.

Applicant's summary and conclusion

Conclusions:

Under the conditions of the study KIO3 was found to result in lower thyroxine in serum, lipid metabolism disorder and retina dysfunction in rats. The NOAEL of KIO3 in rats was determined to be 3000 μg/L. Serum TC level was found to be a sensitive contacting biomarker of excessive iodine.

Executive summary:

The repeated dose toxicity of the test material was investigated in a study in which groups of 10 female rats were administered test material, in drinking water, over a period of 13 weeks. Animals were dosed at 3000, 6000, 12 000, 24 000, 48 000, 96 000 and 192 000 µg/L, a concurrent control group was administered with plain drinking water. At the end of the treatment period, after electroretinogram examination on selected rats, all animals were sacrificed. Haematology and clinical chemistry examinations were performed. Internal organs were weighed and examined histopathologically.

 

The levels of serum TT4, TT3 and rT3 increased with increasing doses of KIO3, while total cholesterol (TC), triglyetide (TG) in serum and white blood cell (WBC) rose significantly in animals dosed at 6000 μg/L and above (P < 0.05). In addition, the amplitude of a and b waves of ERG were significantly lower in the highest KIO3 group rats compared to the control rats (P < 0.05).

Under the conditions of the study, KIO3 was found to result in lower thyroxine in serum, lipid metabolism disorder and retina dysfunction in rats. The NOAEL of KIO3 in rats was determined to be 3000 μg/L. Serum TC level was found to be a sensitive contacting biomarker of excessive iodine.