Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental toxicity
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. Volume(issue)/page/year: 22,963,1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: OECD 421 (Reproductive and Developmental Toxicity Screening Test)
Principles of method if other than guideline:
The above experiment was performed for toxicological assessment of the test chemical in Sprague-Dawley rats (dams and offspring) when exposed to 0, 0.025, 0.05 or 0.1% (w/w) in the diet.
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
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): 166.0 g/mol- Substance type: Inorganic- Physical state: Solid
Specific details on test material used for the study:
- Molecular weight (if other than submission substance): 166.0 g/mol
- Substance type: Inorganic
- Physical state: Solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Laboratory Supply Co., Inidanapolis, IN
- Weight at study initiation: 200-240 g
- Diet (e.g. ad libitum): Purina rat chow
- Acclimation period: 5 days
- Sex: Male/ Female

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
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No Data Available
Details on mating procedure:
- Proof of pregnancy: The day on which sperm were found was considered to be day 0 of gestation.
- M/F ratio per cage: No data available
- Length of cohabitation: 1-4 days
- Proof of pregnancy: The day on which sperm were found was considered to be day 0 of gestation.
- Any other deviations from standard protocol: No data available
Duration of treatment / exposure:
Male: 2 week(s) pre-mating
Female: 2 week(s) pre-mating to 13 day(s) post-birth
Offspring: After weaning upto 90 days of age
Frequency of treatment:
Daily
Duration of test:
Males: 14 days before mating and during 1-4 days of breeding
Females: 14 days before mating, 1-4 days of breeding, 22 days of gestation and 21 days of lactation
Offspring: After weaning, up to 90 days of age
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, About 23,45 and 90 mg/kg bw
Basis:
nominal in diet
for parents
Remarks:
Doses / Concentrations:
0,About 42,81 and 160 mg/kg bw
Basis:
nominal in diet
for offspring
No. of animals per sex per dose:
Negative control: 22 pregnant females
Positive control: 27 pregnant females
0.025% (w/w) test chemical: 30 pregnant females
0.05% (w/w) test chemical: 26 pregnant females
0.1% (w/w) test chemical: 19 pregnant females
Control animals:
yes, concurrent vehicle
Details on study design:
- Positive-control: Dams were given two ip injections of 2 mg/kg of 5-azacytidine on day 17 of gestation.

- Other: Litters with fewer than eight live offspring were not kept beyond 1 day after birth. Litters of more than 12 were reduced to 12 by a random selection procedure that balanced the sex distribution as much as possible

Examinations

Maternal 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.
Ovaries and uterine content:
No data available
Fetal examinations:
- 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.
- Vaginal patency was noted daily on females
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 unequal group sizes were made. On all tests litter was used as the unit of analysis. Frequency data were analysed using Fisher's test for uncorrelated proportions.
Indices:
No data available
Historical control data:
No data available

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No changes in the maternal body weights were observed at any given dose levels.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Maternal food consumption was reduced during lactation in the 0.025% (w/w) of the test chemical.
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
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
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
effects observed, treatment-related
Description (incidence and severity):
The test chemical produced significant increased mortality in offspring in the 0.1% (w/w) group at birth and up to day 24 after birth. The 0.025% (w/w) of the test chemical group, by contrast, showed reduced mortality up to day 24.
Changes in pregnancy duration:
no effects observed
Description (incidence and severity):
Gestation time for rats was not affected by the test chemical
Changes in number of pregnant:
not specified
Other effects:
effects observed, treatment-related
Description (incidence and severity):
Gestation time for rats was not affected by the test chemical; however, prolonged parturition was observed in rats.No signs of the beginning of lactation were observed.
Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
- A reduction in male, but not female, food consumption was found in the 90 mg/kg of test chemical group prior to breeding, resulting in only a marginal decrease in body weight.
- No effects were found on maternal food consumption or body weight during gestation.
- Maternal food consumption was reduced during lactation in the 0.025% (w/w) of the test chemical.
- The test chemical significantly deccreased the proportion of litters born with less than eight live offspring at the highest dose 0.1% (w/w).

Effect levels (maternal animals)

open allclose all
Dose descriptor:
LOAEL
Effect level:
0.025 other: % (w/w) per day
Based on:
test mat.
Basis for effect level:
other: developmental toxicity
Dose descriptor:
LOAEL
Effect level:
0.025 other: % (w/w) per day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Fetal body weight changes:
effects observed, treatment-related
Description (incidence and severity):
The test chemical decreased body weights in both the 0.1 and 0.05% (w/w) groups. These effects were virtually identical for both males and females and were significant on days 14 and 21 in the test chemical groups, but not earlier. There were no significant weight reductions found in the 0.025% (w/w) group.
Reduction in number of live offspring:
not specified
Changes in sex ratio:
not specified
Changes in litter size and weights:
not specified
Changes in postnatal survival:
not specified
Description (incidence and severity):
The test chemical produced significant increased mortality in offspring in the 0.1% (w/w) group at birth and up to day 24 after birth. The 0.025% (w/w) of the test chemical group, by contrast, showed reduced mortality up to day 24.
External malformations:
no effects observed
Description (incidence and severity):
Upper and lower incisor eruption and eye opening were unaffected by treatment. No significant group effects were found on vaginal patency or on testicular development.
Skeletal malformations:
not specified
Visceral malformations:
no effects observed
Description (incidence and severity):
No significant effect was found on absolute or relative thyroid weight at 90 days of age. No effects were found on cerebellar or total brain weights. The medulla pons showed a significantly reduced weight in the 0.1% (w/w) of the test chemical group only.
Other effects:
effects observed, treatment-related
Description (incidence and severity):
- Test chemical delayed auditory startle at the two highest doses by 1 day but did not significantly affect surface-righting or negative geotaxis behaviour and the behavioral tests of active or passive avoidance learning.
- The 0.025% (w/w) and 0.05% (w/w) of the test chemical groups showed delayed olfactory orientation towards their home-cage scent, but only in the 0.025% (w/w) group the delay was significant
- Open field activity: All groups except 0.1% (w/w) showed shorter starting latencies.
- Running wheel activity: females in all groups were significantly less active during dark cycle. There was no significant difference among males.
- M-maze: The 0.025% (w/w) of the test chemical group made significantly more errors on the swimming M-maze
- Rotorod: the 0.025% (w/w) of the test chemicalgroup required significantly more trials to reach criterion
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
Mortality:
he test chemical produced significant increased mortality in offspring in the 0.1% (w/w) group at birth and up to day 24 after birth. The 0.025% (w/w) of the test chemical group, by contrast, showed reduced mortality up to day 24.

Body weights:
The test chemical decreased body weights in both the 0.1 and 0.05% (w/w) groups. These effects were virtually identical for both males and females and were significant on days 14 and 21 in the of the test chemical groups, but not earlier. There were no significant weight reductions found in the 0.025% (w/w) group.

Organ weights:
No significant effect was found on absolute or relative thyroid weight at 90 days of age. No effects were found on cerebellar or total brain weights. The medulla pons showed a significantly reduced weight in the 0.1% (w/w) of the test chemical group only.

Physical milestones:
Upper and lower incisor eruption and eye opening were unaffected by treatment.
No significant group effects were found on vaginal patency or on testicular development.

Reflex behaviour:
- The test chemical delayed auditory startle at the two highest doses by 1 day but did not significantly affect surface-righting or negative geotaxis behaviour and the behavioral tests of active or passive avoidance learning.
- The 0.025% (w/w) and 0.05% (w/w) test chemical groups showed delayed olfactory orientation towards their home-cage scent, but only in the 0.025% (w/w) group the delay was significant
- Open field activity: All groups except 0.1% (w/w) showed shorter starting latencies.
- Running wheel activity: Females in all groups were significantly less active during dark cycle. There was no significant difference among males.
- M-maze: The 0.025% (w/w) test chemical group made significantly more errors on the swimming M-maze.
- Rotorod: the 0.025% (w/w) test chemical group required significantly more trials to reach criterion.

Effect levels (fetuses)

Dose descriptor:
LOAEL
Effect level:
0.025 other: % (w/w) per day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
fetal/pup body weight changes
changes in postnatal survival
visceral malformations
other:
Remarks on result:
other: Not Specified

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental 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 chemicalwas 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.