Registration Dossier

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

Administrative data

Endpoint:
chronic toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
publication
Title:
The Toxicology of Potassium and Sodium lodates II. Subacute Toxicity of Potassium lodate in Mice and Guinea Pigs
Author:
STEWART H. WEBSTER, MARY E. RICE, BENJAMIN HIGHMAN, AND EDWARD F. STOHLMAN
Year:
1959
Bibliographic source:
TOXICOLOGY 1, 87-96 (1959)

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other:
Principles of method if other than guideline:
Toxicity of potassium iodate was assessed in Swiss mice
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material : Potassium iodate
- Molecular formula : KIO3
- Molecular weight : 214.001
- Substance type : Inorganic
- Physical state : Solid

Test animals

Species:
mouse
Strain:
Swiss
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data available
- Age at study initiation: No data available
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: Mice were was housed in glass jars embedded with saw dust.
- Diet (e.g. ad libitum): Purina Laboratory Chow, ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimatization period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%) :No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available

IN-LIFE DATES: From: To: No data available



Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS:
KIO3 was administered to comparable groups of mice in their drinking water.

DIET PREPARATION
- Rate of preparation of diet (frequency): N/A
- Mixing appropriate amounts with (Type of food): N/A
- Storage temperature of food: N/A

VEHICLE
- Justification for use and choice of vehicle (if other than water): Water
- Concentration in vehicle: 0, 0.05, 0.10, 0.25, 0.50 or 0.75% per day
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
104 days
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0.05%, 0.10%, 0.25%, 0.50%, and 0.75% (71.428, 142.857, 357.142, 714.285, 1071.428 mg/kg bw/day)
Basis:
nominal in water
No. of animals per sex per dose:
76
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No
- Time schedule:
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: No
- Time schedule:

BODY WEIGHT: Yes
- Time schedule for examinations: Twice weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No

FOOD EFFICIENCY: No
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: Twice weekly

OPHTHALMOSCOPIC EXAMINATION: No
- Time schedule for examinations:
- Dose groups that were examined:

HAEMATOLOGY: Yes
- Time schedule for collection of blood: No data available
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals: On all surviving animals.
- Parameters examined: Potassium iodate and potassium iodide

CLINICAL CHEMISTRY: No
- Time schedule for collection of blood:
- Animals fasted:
- How many animals:
- Parameters examined:

URINALYSIS: No
- Time schedule for collection of urine:
- Metabolism cages used for collection of urine:
- Animals fasted:
- Parameters examined:

NEUROBEHAVIOURAL EXAMINATION: No
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / other:



Sacrifice and pathology:
GROSS PATHOLOGY: Yes
Survivors were killed with ether at the end of the experiment for pathologic study. Autopsies were performed also on all animals that died during the experiment.

HISTOPATHOLOGY: Yes
Tissues saved for microscopic study were fixed in 10% aqueous buffered formalin (pH 7.0).
Statistics:
Statistical tests were carried out on the hematologic data using Student’s t-test.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
Clinical signs and mortality:
Three animals in the 0.75% per day group died during the first week.

Body weight and weight gain
Increased in body weight observed in all dose groups at 104th day.

Food consumption and compound intake
No data available

Water consumption and compound intake
At the beginning of the experiment the 0.75%/day KIO3 group drank only about 25% as much as the controls, but later the consumption increased to between 60% and 70% of the control group. However, controls and mice given lower concentrations of iodate drank less liquid as they grew larger. Accordingly, it seems reasonable to conclude that the restriction of liquid by the mice given the higher iodate concentrations may be due to the bad taste and/or toxic effects of the drinking water. It is likely that the reduced consumption of liquid is accompanied by a decrease in the amount of food ingested or vice versa, which would result in a decreased growth rate.

Haematology
Decreased levels of RBC, hemoglobin, hematocrit and WBC count were observed as compared to control.

Clinical chemistry
No data available

Organ weights
No data available

Gross pathology
No gross abnormalities attributable to iodate were found at autopsy. In only three of twenty-four iodate animals was the pH of the stomach contents increased above 4.

Histopathology
None of the animals showed histologic alterations in the gastric mucosa. Microscopic studies showed hemosiderin deposits in the renal convoluted tubules in nearly all mice which received 0.50%/day KIO3 for 16 weeks. Similar changes were seen in only a few mice which received distilled water, iodide, or lower concentrations of iodate. The deposition of hemosiderin, in addition to the reduced blood values is strong evidence of increased hemolysis due to the iodate. No other significant changes were found.

Effect levels

open allclose all
Dose descriptor:
LOEL
Effect level:
714.285 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: Body weight, water consumption and increased hemolysis.
Dose descriptor:
NOAEL
Effect level:
357.142 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: Water consumption and increased hemolysis.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
LOEL was considered to be 0.50% (714.285 mg/kg bw/day) while NOAEL was considered to be 0.25% (357.142 mg/kg bw/day )per day when Swiss female mice were exposed to KIO3.
Executive summary:

In a toxicity study, the effect of potassium iodate (KIO3) was assessed in Swiss female mice. The mice were exposed to KIO3in drinking water on a daily basis at dose concentration of 0,0.05, 0.10, 0.25%, 0.50 or 0.75% per day for 104 days. Increasedin body weight was observed in all dose groups at the end of the study. Decreased levels of RBC, hemoglobin, hematocrit and WBC count were also observed as well as deposition ofhemosiderin in the renal convoluted tubules in nearly all mice receiving 0.50%/day KIO3for 16 weeks. Deposition of hemosiderin, in addition to the reduced blood values, is strong evidence of increased hemolysis due to the iodate treatment. Hence, LOEL was considered to be 0.50% (714.285 mg/kg bw/day) whereas NOAEL was considered to be 0.25% (357.142 mg/kg bw/day ) in Swiss female mice when exposed to KIO3in drinking water on a daily basis for 16 weeks.