Potassium iodide

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

experimental study

Adequacy of study:

key 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 a publication.

Data source

Reference

Reference Type:

publication

Title:

Developmental toxicity and psychotoxicity of potassium iodide in rats: a case for the inclusion of behaviour in toxicological assessment.

Author:

Vorhees CV, Butcher RE, Brunner RL

Year:

1984

Bibliographic source:

Food and Chemical Toxicology, 1984 Dec; Vol 22 (12): 963-970

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

Principles of method if other than guideline:

The above experiment was performed to examine and analyze the reproductive toxicity of the test chemical in Sprague Dawley Rats.

GLP compliance:

not specified

Limit test:

no

Justification for study design:

No Data Available

Test material

Test material information

Constituent 1

Reference substance name:

Potassium iodide

EC Number:

231-659-4

EC Name:

Potassium iodide

Cas Number:

7681-11-0

Molecular formula:

IK

IUPAC Name:

potassium iodide

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report):potassium iodide- Molecular formula (if other than submission substance): KI- Molecular weight (if other than submission substance): 166.00- Substance type: Inorganic- Physical state: Solid

Specific details on test material used for the study:

- Molecular weight (if other than submission substance): 166.00
- Substance type: Inorganic
- Physical state: Solid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on species / strain selection:

No Data Available

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Laboratory Supply Co., Indianapolis, IN
- Weight at study initiation: 200-240 g
- Diet (e.g. ad libitum): Purina rat chow meal
- Acclimation period: 5 days

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: Purina rat chow meal

Details on exposure:

The newborn offspring were exposed through lactating females until weaning

Details on mating procedure:

Details of mating
- M/F ratio per cage: No data available
- Length of cohabitation: No data available
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy: The day on which sperm were found was considered to be day 0 of gestation.
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility. No Data Available
- Further matings after two unsuccessful attempts: [no / yes (explain)]: No Data Available
- After successful mating each pregnant female was caged (how): No Data Available

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No Data Available

Duration of treatment / exposure:

Males: 28 days
Females: 71 days

Frequency of treatment:

Daily

Details on study schedule:

Males: 14 days before mating and for 1-14 days during breeding
Females: 14 days before mating and for 1-14 days during breeding; during gestation (22 days) and lactation (21 days).

Doses / concentrations

Remarks:

Doses / Concentrations:
0, About 23,45 and 90 mg/kg bw /day
Basis:
nominal in diet
0, 0.025, 0.05 or 0.1% (w/w)

No. of animals per sex per dose:

No Data Available

Control animals:

yes, concurrent vehicle

Details on study design:

No Data Available

Positive control:

Dams were given two i.p. injections of 2 mg/kg of S-azacytidine on day 17 of gestation.

Examinations

Parental animals: Observations and examinations:

BODY WEIGHT: Yes
- Time schedule for examinations: Parental body weights were measured at weekly intervals except during breeding, and food consumption was measured on selected rats during all phases of the experiment.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
The test chemical doses, calculated from food consumption measurements, for the 0.025% test chemical group were 22, 22 and 34 mg/kg/day prior to breeding, during gestation and during lactation, respectively, for females; for the 0.05% test chemical group they were 46, 44 and 66 mg/kg/day; and for the 0.1% test chemical group they were 93, 92 and 140 mg/kg/day respectively.

Oestrous cyclicity (parental animals):

No Data Available

Sperm parameters (parental animals):

No Data Available

Litter observations:

PARAMETERS EXAMINED
The following parameters were examined in [F1 / F2 / F3] offspring:
Incisor eruption was observed daily from day 8 until all incisors were visible. Eye opening was observed daily from day 10 until both eyes were fully open in all rats. Testicular development was checked each day from day 10 until both testes could first be seen as two small nodules in the scrotum. On the day following birth, all litters were examined and data collected on litter size, sex distribution, weight, and number of dead and/or malformed offspring.
.

Postmortem examinations (parental animals):

No Data Available

Postmortem examinations (offspring):

No Data Available

Statistics:

Analysis of variance (ANOVA) was performed on the majority of data (general linear model), and Duncan's pairwise comparisons made between individual groups in the event of significant treatment F-ratios. Adjustments of Duncan's test for un-equal group sizes were made using the procedure of Kramer.

Reproductive indices:

No Data Available

Offspring viability indices:

Pup Viability Index

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality:

not specified

Body weight and weight changes:

effects observed, non-treatment-related

Description (incidence and severity):

A reduction in male (P < 0.01), but not female, body weight was found in the 0. 1% test chemical group prior to breeding. Although, these cases were considered as sporadic.

Food consumption and compound intake (if feeding study):

effects observed, non-treatment-related

Description (incidence and severity):

A reduction in male (P < 0.01), but not female, feed consumption was found in the 0. 1% test chemical group prior to breeding. Although, these cases were considered as sporadic.

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Description (incidence and severity):

No significant effects on parental mortality, fertility, pregnancy parameters, or gestation length were observed at any dose groups.

Effect levels (P0)

Dose descriptor:

LOAEL

Effect level:

ca. 90 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Target system / organ toxicity (P0)

Critical effects observed:

not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Description (incidence and severity):

Upper and lower incisor eruption and eye opening were unaffected by treatment with the test chemical.

Dermal irritation (if dermal study):

not specified

Mortality / viability:

mortality observed, treatment-related

Description (incidence and severity):

The test chemical produced significant increases in offspring mortality in the 90 mg/kg group at birth and up to day 24 after birth.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

The test chemical decreased preweaning body weights in both the 90 and 45 mg/kg groups

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Sexual maturation:

no effects observed

Description (incidence and severity):

Testicular development was unaffected by treatment with the test chemical.

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

No significant effect was found on absolute or relative thyroid and testes weights at 90 days of age.

Gross pathological findings:

not specified

Histopathological findings:

not specified

Other effects:

not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):

not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:

not specified

Details on results (F1)

Reflex behaviour:
• Test chemical delayed auditory startle at the two highest doses by 1 day but did not significantly affect surface-righting or negative geotaxis behaviour.
• The 45mg/kg and 90 mg/kg of the test chemical groups showed delayed olfactory orientation towards their home-cage scent, but only in the 45mg/kg group the delay was significant

Effect levels (F1)

Dose descriptor:

LOAEL

Generation:

F1

Effect level:

ca. 45 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Decreased pre-weaning body weights, delay in auditory startle and delayed olfactory orientation from the home-cage scent

Target system / organ toxicity (F1)

Critical effects observed:

not specified

Overall reproductive toxicity

Reproductive effects observed:

not specified

Treatment related:

not specified

Applicant's summary and conclusion

Conclusions:

From all the above observations, it was concluded that the LOAEL for the test chemical was found to be 45 mg/kg bw.

Executive summary:

The above experiment was performed to study the effect of ingestion of the test chemical by parental examinations on the behavioural competence of developing animals is studied.The test chemical was administered in diet to male and female Sprague-Dawley rats before and during breeding, to females only during gestation and lactation, at levels of 0, about 23,45 and 90 mg/kg bw [0, 0.025, 0.05 or 0.1% (w/w)]. Dams in a positive control group were given 4 mg/kg ip of the anti-mitotic/cytotoxic drug 5-azacytidine on day 17 of gestation. The LOAEL value for the test chemical in rats is found to be about 90 mg/kg/day (0.1%). At this dose level, the test chemical did not produce any significant reduction in parental body weight or food consumption, though it significantly reduced litter size and increased offspring mortality. The LOAEL value for the test chemical is found to be about 45 mg/kg/day (0.05%) for the F1 generation based on the effect of decreased pre-weaning body weights in the offspring, delay in auditory startle and delayed olfactory orientation from the home-cage scent. Overall, the data in this experiment support the view that the test chemical at doses of up to 0.1% in the diet of growing rats produces evidence of developmental toxicity.