Registration Dossier

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental 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

Reference
Name:
Unnamed
Type:
Constituent
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

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Dietary treatments were given continuously to both males and females for 14 days before mating and for 1-14 days during breeding, and to females only during gestation (22 days) and lactation (21 days).
Frequency of treatment:
Daily in food
Duration of test:
Parents (males and females): 14 days before mating; 1-14 days during breeding.
Females only (mothers): during gestation (22 days) and lactation (21 days)
Offspring: given dietary potassium iodide, at the level their parents had received, throughout the remainder of the experiment (up to 90 days of age for most animals and somewhat longer for those in avoidance testing).
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:
No data
Control animals:
yes
yes, concurrent no treatment

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
BODY WEIGHT: Yes
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
Fetal examinations:
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.

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
not specified
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 specified
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
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Maternal developmental toxicity

Number of abortions:
not specified
Pre- and post-implantation loss:
not specified
Early or late resorptions:
not specified
Dead fetuses:
not specified
Changes in pregnancy duration:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified
Changes in number of pregnant:
not specified
Other effects:
not specified

Effect levels (maternal animals)

Key result
Dose descriptor:
NOAEL
Effect level:
0.1 other: % in diet
Based on:
test mat.
Basis for effect level:
other: no adverse effects at the highest tested dose

Maternal abnormalities

Key result
Abnormalities:
no effects observed

Results (fetuses)

Fetal body 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.
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): effects observed, treatment-related
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.DescriptionIncidenceAndSeverityFetalPupBodyWeightChanges): KI produced decreased weight gain at the two highest doses throughout the first 90 days after birth.
Reduction in number of live offspring:
effects observed, treatment-related
Description (incidence and severity):
KI significantly increased offspring mortality at the highest dose.
Changes in sex ratio:
not specified
Changes in litter size and weights:
effects observed, treatment-related
Description (incidence and severity):
KI significantly reduced litter size at the highest dose.
Changes in postnatal survival:
effects observed, treatment-related
Description (incidence and severity):
KI significantly increased offspring mortality at the highest dose.
External malformations:
no effects observed
Skeletal malformations:
not specified
Visceral malformations:
not specified
Other effects:
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.
Details on embryotoxic / teratogenic effects:
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

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
0.025 other: % in diet
Based on:
test mat.
Sex:
not specified
Basis for effect level:
reduction in number of live offspring
fetal/pup body weight changes
changes in litter size and weights
changes in postnatal survival
other: 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

Fetal abnormalities

Key result
Abnormalities:
no effects observed

Overall developmental toxicity

Key result
Developmental effects observed:
yes
Lowest effective dose / conc.:
0.05 other: % in diet
Treatment related:
yes
Relation to maternal toxicity:
developmental effects in the absence of maternal toxicity effects
Dose response relationship:
yes
Relevant for humans:
yes

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 was 0.025% in diet.