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Toxicity to reproduction

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Administrative data

Endpoint:
one-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

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, Vol 22 (12): 963-970

Materials and methods

Principles of method if other than guideline:
Potassium iodide was fed to male and female rats before and during breeding, to females only during gestation and lactation, and to their offspring after weaning (day 21 after birth) through to day 90, at levels of 0, 0.025, 0.05 or 0.1% (w/w) of the diet. The screening test battery of Cincinnati Psychoteratogenicity for rats as the method for assessing the psychotoxic potential of potassium iodide was used to investigate the hazard effects to parents and developmental toxic effects to embryo and offspring in 90 days.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
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
Details on test material:
Food grade potassium iodide (Mallinckrodt Inc.) was purchased from the Tab Chemical Company, Chicago, IL.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Potassium iodide was fed to male and female rats before and during breeding, to females only during gestation and lactation, and to their offspring after weaning (day 21 after birth) through to day 90, at levels of 0, 0.025, 0.05 or 0.1% (w/w) of the diet. The screening test battery of Cincinnati Psychoteratogenicity for rats as the method for assessing the psychotoxic potential of potassium iodide was used to investigate the hazard effects to parents and developmental toxic effects to embryo and offspring in 90 days.
Frequency of treatment:
Daily in feed
Doses / concentrationsopen allclose all
Dose / conc.:
0.025 other: % in diet
Dose / conc.:
0.05 other: % in diet
Dose / conc.:
0.1 other: % in diet
No. of animals per sex per dose:
Not specified
Control animals:
yes, concurrent no treatment
Positive control:
A separate group of dams (positive controls) were given 4 mg/kg bw ip of the anti-mitotic/cytotoxic drug 5-azacytidine on day 17 of gestation.

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): yes
Litter observations:
All offspring were reared by their natural dams and were evaluated blind with respect to treatment in a battery of standardized behavioural tests between 3 and 90 days of age. The following parameters were further examined: litter size, birth weight, external malformations, offspring mortality, body weight and weight gain, brain and thyroid weight.
Postmortem examinations (offspring):
Brain and thyroid weights were determined.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Mortality:
not specified
Body weight and weight changes:
no effects observed
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 examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
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 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

Details on results (P0)

KI produced no significant reductions in parental body weight or food consumption

Effect levels (P0)

Key result
Dose descriptor:
NOAEL
Effect level:
0.1 other: % in diet
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no adverse effects observed at the highest tested dose
Remarks on result:
not determinable due to absence of adverse toxic effects

Target system / organ toxicity (P0)

Critical effects observed:
no

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Mortality / viability:
mortality observed, treatment-related
Description (incidence and severity):
KI significantly increased offspring mortality at the highest dose.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
KI produced decreased weight gain at the two highest doses throughout the first 90 days after birth.
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
In rats killed on day 90 after birth KI reduced brain and body weight at a dose of 0.1% of the diet, and reduced body but not brain weight at a dose of 0.05% of the diet. No significant effect was found on absolute or relative thyroid weight at 90 days of age.
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
effects observed, treatment-related
Description (incidence and severity):
Functionally, KI delayed auditory startle at the two highest doses, delayed olfactory orientation to the home-cage scent at the middle dose and decreased female running-wheel activity at all dose levels.

Developmental neurotoxicity (F1)

Behaviour (functional findings):
effects observed, treatment-related
Description (incidence and severity):
Functionally, KI delayed auditory startle at the two highest doses, delayed olfactory orientation to the home-cage scent at the middle dose and decreased female running-wheel activity at all dose levels.

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not examined

Effect levels (F1)

Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
0.025 other: % in diet
Based on:
test mat.
Sex:
male/female
Basis for effect level:
mortality
body weight and weight gain

Target system / organ toxicity (F1)

Key result
Critical effects observed:
yes
Lowest effective dose / conc.:
0.05 other: % in diet
System:
endocrine system
Organ:
thyroid gland

Overall reproductive toxicity

Key result
Reproductive effects observed:
yes
Lowest effective dose / conc.:
0.05 other: % in diet
Treatment related:
yes
Relation to other toxic effects:
reproductive effects in the absence of other toxic effects
Dose response relationship:
yes
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
In the study with rats, in which potassium iodide was administered in diet at 0.025%, 0.05% and 0.1% to male and female rats before and during breeding, to females only during gestation and lactation, and to their offspring after weaning (day 21 after birth) through to day 90, the NOAEL for developmental toxicity was 0.025% in diet, based on decreased body weight and weight gain and delayed auditory startle at the two top dose levels. The NOAEL for parental toxicity was 0.1% in diet.
Executive summary:

Potassium iodide (KI) was fed to male and female rats before and during breeding, to females only during gestation and lactation, and to their offspring after weaning (day 21 after birth) through to day 90, 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 bw ip of the anti-mitotic/cytotoxic drug 5-azacytidine on day 17 of gestation. All offspring were reared by their natural dams and were evaluated blind with respect to treatment in a battery of standardized behavioural tests between 3 and 90 days of age. KI produced no significant reductions in parental body weight or food consumption, though it significantly reduced litter size and increased offspring mortality at the highest dose, and decreased weight gain at the two highest doses throughout the first 90 days after birth. Functionally, KI delayed auditory startle at the two highest doses, delayed olfactory orientation to the home-cage scent at the middle dose and decreased female running-wheel activity at all dose levels. In rats killed on day 90 after birth KI reduced brain and body weight at a dose of 0.1% of the diet, and reduced body but not brain weight at a dose of 0.05% of the diet. No significant effect was found on absolute or relative thyroid weight at 90 days of age. Several additional behavioural effects were observed in the low-dose KI group, but because these effects were not dose-dependent, they were not regarded as reliable. 5-Azacytidine produced evidence of substantially greater developmental toxicity than KI. It was concluded that KI produced evidence of developmental toxicity consistent with a picture of impaired thyroid function. The parental NOEL value for potassium iodide in rats was 0.1% in diet, while the NOAEL for offspring was0.025% in diet.


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