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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
one-generation reproductive toxicity
Remarks:
based on test type (migrated information)
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:
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:
according to
Guideline:
other:
Principles of method if other than guideline:
Potassium iodide (KI) was fed to male and female rats before and during breeding, to females only during gestation and lactation, at levels of 0, 0.025, 0.05 or 0.1% (w/w) of the diet. Dams in a fifth group (positive controls) were given 4 mg/kg ip of the anti-mitotic/cytotoxic drug 5-azacytidine on day 17 of gestation. The rats were evaluated for effects.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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:
- Proof of pregnancy: The day on which sperm were found was considered to be day 0 of gestation
Analytical verification of doses or concentrations:
not specified
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
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 potassium iodide doses, calculated from food consumption measurements, for the 0.025% potassium iodide group were 22, 22 and 34 mg/kg/day prior to breeding, during gestation and during lactation, respectively, for females; for the 0.05% potassium iodide group they were 46, 44 and 66mg/kg/day; and for the 0.1% potassium iodide group they were 93, 92 and 140 mg/kg/day respectively.
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.
The reduction in weight in the 90 mg/kg group was 7.7% on day 14 and 7.3% on day 21, for males and females combined. The reduction in weight in the 45 mg/kg group was 12.5% on day 14 and 6.8% on day 21, males and females combined.
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.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not examined
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
minor effects on parental weight gain and food consumption
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
minor effects on parental weight gain and food consumption
Organ weight findings including organ / body weight ratios:
not examined
Histopathological findings: non-neoplastic:
not examined
Other effects:
not examined

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed
Description (incidence and severity):
no significant effects on parental mortality, fertility, pregnancy maintenance, or gestation length

Effect levels (P0)

Dose descriptor:
LOEL
Effect level:
ca. 90 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: see 'Remark'

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.
Mortality / viability:
mortality observed, treatment-related
Description (incidence and severity):
Potassium iodide 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):
Potassium iodide decreased preweaning body weights in both the 90 and 45 mg/kg groups
Sexual maturation:
no effects observed
Description (incidence and severity):
Testicular development was unaffected by treatment.
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 weight at 90 days of age.
Gross pathological findings:
not examined
Histopathological findings:
not examined

Details on results (F1)

Reflex behaviour:
• KI 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 potassium iodide 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:
LOEL
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

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The LOEL value for potassium iodide administered in diet to Sprague-Dawley rats is found to be about 90 mg/kg/day (0.1%)
At this dose level, KI produced no significant reductions in parental body weight or food consumption, though it significantly reduced litter size and increased offspring mortality.

For the F1 generation, the LOEL value was found to be about 45 mg/kg/day (0.05%) 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.
Executive summary:

The effect of ingestion of potassium iodide by parents on the behavioural competence of developing animals is studied.

 

Potassium iodide (KI) 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 LOEL value for potassium iodide in rats is found to be about 90 mg/kg/day (0.1%). At this dose level, KI did not produce any significant reduction in parental body weight or food consumption, though it significantly reduced litter size and increased offspring mortality.

 

The LOEL value for potassium iodide 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 potassium iodide at doses of up to 0.1% in the diet of growing rats produces evidence of developmental toxicity.