Potassium iodide

Endpoint summary

Description of key information

Repeated dose toxicity: Oral

In a combined carcinogenicity and chronic toxicity study, the test chemical was orally administered in drinking water to male and female F344/DuCrj rats. The rats were given the test chemical at concentrations of 0, 10, 100 or 1000 ppm for up to 104 weeks. These doses are equivalent to approx. 0.55. 5.31 or 55.03 mg/kg/day in males and approx. 0.66, 6.73 or 66.59 mg/kg/day in females. The treated animals were observed for mortality, clinical signs, body weight changes, hematology and were subjected to gross and histopathology. The incidence of thyroid follicular dilatation was increased in the 10, 100 and 1000 ppm groups of both sexes. The results showed no systemic toxic effects, however, a depression in body weights and induction of squamous cell carcinomas in the salivary glands were observed at 1000 ppm. Based on the observations made, the low observed adverse effect level (LOAEL) for the test chemical was determined to be 0.55 mg/kg/day (100 ppm) in F344/ DuCrj rats as no systemic toxic effects were observed.

Repeated dose toxicity: Inhalation

Potassium iodide (CAS no. 7681-11-0)has very a low vapor pressure of1 mm Hg at 745 ˚C. The particle size distribution was determined to be in the range of 225 micron to 500 micron. The normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely. Therefore this end point for repeated dose toxicity by inhalation route is considered for waiver

Repeated dose toxicity: Dermal

The acute dermal toxicity value for Potassium iodide (CAS no. 7681-11-0) (as provided in section 7.2.3) is >2000 mg/kg body weight. Considering this, the end point for repeated dermal toxicity is considered as waiver.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: oral

Remarks:

combined repeated dose and carcinogenicity

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed publication

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Combined carcinogenicity and chronic toxicity study was performed in rats to determine the toxic nature of the test chemical upon repeated exposure by oral route

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Fischer 344/DuCrj

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan (Atsugi, Japan)
- Age at study initiation: 6 weeks
- Housing: Animals were housed two or three in a polycarbonate cage with wood chips for bedding.
- Diet (e.g. ad libitum): CRF-1 diet (Oriental Yeast, Tokyo, Japan), ad libitum
- Water (e.g. ad libitum): Distilled water, ad libitum
- Acclimatization period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24±1°C
- Humidity (%): 55±5%
- Air changes (per hr): 18 times/hour
- Photoperiod (hrs dark / hrs light): 12-hrs light/12-hrs dark

Route of administration:

oral: drinking water

Vehicle:

water

Remarks:

Distilled water

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: The test chemical was added to the drinking water to give dose level of 0, 10, 100 and 1000 ppm (equal to approx. 0, 0.55, 5.31 or 55.03 mg/kg/day in males and 0, 0.66, 6.73 or 66.59 mg/kg/day in females)

DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available

VEHICLE
- Justification for use and choice of vehicle (if other than water): Distilled water
- Concentration in vehicle: 0, 10, 100 and 1000 ppm (equal to approx. 0, 0.55, 5.31 or 55.03 mg/kg/day in males and 0, 0.66, 6.73 or 66.59 mg/kg/day in females)
- 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:

2 years

Frequency of treatment:

Daily

Remarks:

Doses / Concentrations: 0, 10, 100 or 1000 ppm (equal to approx. 0, 0.55, 5.31 or 55.03 mg/kg/day in males and 0, 0.66, 6.73 or 66.59 mg/kg/day in females)

No. of animals per sex per dose:

Total: 400 rats
Control: 60 males and 60 females
10 ppm: 40 males and 40 females
100 ppm: 40 males and 40 females
1000 ppm: 60 males and 60 females

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: 1000 ppm was set as the highest dose, exceeding the 260 ppm which has been reported to induce colloid goiter. The lowest dose, 10 ppm, was also higher as compared to the optimal one for the rat, namely 0.2 ppm.
- Rationale for animal assignment (if not random): Only animals showing no abnormalities during a 1-week acclimatization period were used in the study.

Positive control:

No data available

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
- Cage side observations checked in table [No.?] were included. General condition

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule: No data

BODY WEIGHT: Yes
- Time schedule for examinations: every 2 wk up to 12 wk, and every 4 wk thereafter.

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

FOOD EFFICIENCY:
- 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 data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: every 2 wk up to 12 wk, and every 4 wk thereafter.

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

HAEMATOLOGY: Yes
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: All animals
- Parameters checked in table [No.?] were examined. White blood cell count (WBC), red blood cell count (RBC), hemoglobin (Hb), hematocrit (Ht) and platelet count (PLT) were recorded

CLINICAL CHEMISTRY: No data
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

URINALYSIS: No data
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. No data

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

IMMUNOLOGY: No data
- Time schedule for examinations: No data
- How many animals: No data
- Dose groups that were examined: No data
- Parameters checked in table [No.?] were examined. No data

OTHER: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, In the 0 and 1000 ppm groups, five rats each were necropsied 3, 6, 12 and 18 months after the initiation of the treatment. Livers, kidneys, lungs, hearts, spleens, adrenals, brains, pituitaries and thyroids were fixed in 10% neutral buffered formalin, for the interim necropsy. For animals treated for 2 year, in addition to the organs described above, testes, noses, tongues, tracheas, salivary glands, esophagus, stomachs, small and large intestines, pancreas, urinary bladders, prostates, seminal vesicles, ovaries, uteri, vaginae, mammary glands, lymph nodes, sternums, femurs, spinal cords, eye balls, skin and skeletal muscles were fixed in the same manner. Grossly visible lesions were also separately fixed.

HISTOPATHOLOGY: Yes, Histopathological examination was performed on hematoxylin-eosin (HE)-stained specimens processed routinely. Animals that died or were killed in a moribund condition were also necropsied and examined histopathologically.

Other examinations:

No data available

Statistics:

Body weight, water consumption, organ weight and hematology data were analyzed for homogeneity of variance using Bartlett's test. If homogeneous: one-way analysis of variance was applied. If heterogeneous: equivalent non-parametric statistical method of Kruskal-Wallis was applied. Final survival rates and the incidences of tumors were compared with the Fisher's exact probability test.

Clinical signs:

not specified

Mortality:

mortality observed, treatment-related

Description (incidence):

Survival rates of male rats were decreased in the 100 and 1000 ppm groups as compared to the control from around 80 weeks after the initiation of the treatment. The rates for females of any treated groups were similar to that of the controls.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Body weights in the 1000 ppm groups of both sexes were depressed in the latter half of the treatment period.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

no effects observed

Description (incidence and severity):

Water consumption in all treated groups was similar to the control level, and the test chemical consumption was accordingly dose dependent.

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Description (incidence and severity):

Hematological examination did not reveal any effects of the treatments.

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

Animals necropsied at 3, 6, 12 and 18 months after the start of the treatment, the number with follicular dilatation in the thyroid were apparently increased in the 1000 ppm group from 3 months. No treatment-related effects were evident in other organs.

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

The incidence of thyroid follicular dilatation was increased in the 10, 100 and 1000 ppm groups of both sexes. No treatment related induction of any lesions was apparent in the other organs or tissues. In the salivary gland, focal acinar atrophy, ductular proliferation and squamous metaplasias were frequently observed, and SCCs were noted in four males and three females of the 1000 ppm group. Lobular atrophies were well-circumscribed from the surrounding tissue and triangular in shape, suggesting focal lesions related to single ducts, and accompanied by ductular proliferation in most cases. Squamous metaplasias were observed in the epithelium of proliferating ductules, and the morphological continuum to squamous cell carcinomas were observed in these metaplasias.

Histopathological findings: neoplastic:

not specified

Description (incidence and severity):

No treatment related induction of any lesions was apparent in the other organs or tissues. Lesions with incidences more than 25% in one or more groups were, foci of cellular alteration in the liver and hyperplasias of the pituitary in both sexes, C-cell hyperplasias of the thyroid, medullary hyperplasias and pheochromocytomas of the adrenals, and interstitial cell tumors of the testis in males, and cystic endometrial hyperplasias and endometrial stromal polyps of the uterus in females. However, these are all known to spontaneously occur and neither increase in their incidence nor special types of lesions were observed in the treated groups

Other effects:

not specified

Details on results:

In the salivary gland, focal acinar atrophy, ductular proliferation and squamous metaplasias were frequently observed, and SCCs were noted in four males and three females of the 1000 ppm group. Lobular atrophies were well-circumscribed from the surrounding tissue and triangular in shape, suggesting focal lesions related to single ducts, and accompanied by ductular proliferation in most cases. Squamous metaplasias were observed in the epithelium of proliferating ductules, and the morphological continuum to squamous cell carcinomas were observed in these metaplasias.

With regard to animals necropsied 3, 6, 12 and 18 months after the initiation of the treatment, the numbers with follicular dilatation in the thyroid were apparently increased in the 1000 ppm group as compared to the controls from 3 months. No treatment-related effects were evident in other organs.

Dose descriptor:

LOAEL

Effect level:

0.55 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

histopathology: non-neoplastic

Critical effects observed:

not specified

Conclusions:

The low observed adverse effect level (LOAEL) for the test chemical was determined to be 0.55 mg/kg/day (10 ppm) in F344/ DuCrj rats as no systemic toxic effects were observed.

Executive summary:

In a combined carcinogenicity and chronic toxicity study, the test chemical was orally administered in drinking water to male and female F344/DuCrj rats. The rats were given the test chemical at concentrations of 0, 10, 100 or 1000 ppm for up to 104 weeks. These doses are equivalent to approx. 0.55. 5.31 or 55.03 mg/kg/day in males and approx. 0.66, 6.73 or 66.59 mg/kg/day in females. The treated animals were observed for mortality, clinical signs, body weight changes, hematology and were subjected to gross and histopathology. The incidence of thyroid follicular dilatation was increased in the 10, 100 and 1000 ppm groups of both sexes. The results showed no systemic toxic effects, however, a depression in body weights and induction of squamous cell carcinomas in the salivary glands were observed at 1000 ppm. Based on the observations made, the low observed adverse effect level (LOAEL) for the test chemical was determined to be 0.55 mg/kg/day (100 ppm) in F344/ DuCrj rats as no systemic toxic effects were observed.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEL

0.55 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Data is from peer reviewed publication

Additional information

Data available for the target chemical was reviewed to determine its toxic nature. The studies are as mentioned below:

Repeated dose toxicity: Oral

In a combined carcinogenicity and chronic toxicity study, the test chemical was orally administered in drinking water to male and female F344/DuCrj rats. The rats were given the test chemical at concentrations of 0, 10, 100 or 1000 ppm for up to 104 weeks. These doses are equivalent to approx. 0.55. 5.31 or 55.03 mg/kg/day in males and approx. 0.66, 6.73 or 66.59 mg/kg/day in females. The treated animals were observed for mortality, clinical signs, body weight changes, hematology and were subjected to gross and histopathology. The incidence of thyroid follicular dilatation was increased in the 10, 100 and 1000 ppm groups of both sexes. The results showed no systemic toxic effects, however, a depression in body weights and induction of squamous cell carcinomas in the salivary glands were observed at 1000 ppm. Based on the observations made, the low observed adverse effect level (LOAEL) for the test chemical was determined to be 0.55 mg/kg/day (100 ppm) in F344/ DuCrj rats as no systemic toxic effects were observed.

In another study, in a combined repeated oral- carcinogenicity study, the effect of the test chemical on the development of thyroid tumors was studied histologically and biochemically in male Wistar rats. The test chemical was then administered to the rats through their basal diet containing 1000 ppm (10 mg/Kgday) for 20 weeks. The treated rats were obsered for changes in body weight, mortality, organ weight changes, clinical chemistry and were subjected to gross- and histo- pathology. Rats given the test chemical showed no evidence of thyroid tumors. No significant effect was observed on body weight and liver in male rats given the test chemical. However, histological changes such as diffused large follicles and flat follicular epithelium in the central area of the thyroids were observed in male rats exposed to the test chemical. Based on the observations made, the low observed adverse effect level (LOAEL) for the test chemical was considered to be 1000 ppm (100 mg/Kg/day) when male Wistar rats were treated for 20 weeks by repeated oral exposure.

Repeated dose toxicity: Inhalation

Potassium iodide (CAS no. 7681-11-0)has very a low vapor pressure of1 mm Hg at 745 ˚C. The particle size distribution was determined to be in the range of 225 micron to 500 micron. The normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely. Therefore this end point for repeated dose toxicity by inhalation route is considered for waiver

Repeated dose toxicity: Dermal

The acute dermal toxicity value for Potassium iodide (CAS no. 7681-11-0) (as provided in section 7.2.3) is >2000 mg/kg body weight. Considering this, the end point for repeated dermal toxicity is considered as waiver.

Based on the data available for the target chemical, the test chemical exhibits toxic nature upon repeated exposure by oral route of exposure. Hence the test chemical is likely to classify as a STOT RE 1 category toxicant.

Justification for classification or non-classification

Based on the data available for the target chemical, the test chemical exhibits toxic nature upon repeated exposure by oral route of exposure. Hence the test chemical is likely to classify as a STOT RE 1 category toxicant.