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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1975-11-12 to 1975-02-19
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1975
Report date:
1975
Reference Type:
review article or handbook
Title:
Potassium chloride - SIDS Initial Assessment Report for 13th SIAM
Author:
OECD SIDS
Year:
2001
Bibliographic source:
OECD SIDS. Potassium chloride, UNEP Publication: SIDS Initial Assessment Report 13th SIAM. Bern, 6-9 November 2001

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Potassium chloride
EC Number:
231-211-8
EC Name:
Potassium chloride
Cas Number:
7447-40-7
Molecular formula:
ClK
IUPAC Name:
potassium chloride
Specific details on test material used for the study:
- Appearance/state: Fine white crystalline material
- Batch No.: FDA 73-78

Test animals

Species:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: adult female and young adult males
- Weight at study initiation: 215 - 230 g
- Housing: Anmals were individually housed in mesh bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum, fresh tap water

ENVIRONMENTAL CONDITIONS
- Temperature: controlled, 72 - 98 °F
- Humidity (%): 40-74

Administration / exposure

Route of administration:
oral: gavage
Details on mating procedure:
- Impregnation procedure: cohoused, males were not allowed to impregnate more than one female per group.
- Proof of pregnancy: Observation of vaginal plug referred to as day 0 of gestation
Duration of treatment / exposure:
Females were dosed beginning on day 6 and continuing through day 15 of gestation.
Frequency of treatment:
daily
Duration of test:
Until gestation day 20
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Remarks:
Control
Dose / conc.:
3.1 mg/kg bw/day
Dose / conc.:
14.4 mg/kg bw/day
Dose / conc.:
66.8 mg/kg bw/day
Dose / conc.:
310 mg/kg bw/day
No. of animals per sex per dose:
21-28 female animals were mated per dose group
Control animals:
yes, concurrent vehicle
Details on study design:
Beginning on day 6 and continuing daily through day 15 of gestation, the females were dosed with 0, 3.1,14.4, 66.8 and 310 mg/kg bw/day potasium chloride by oral intubations. The controls were sham treated with the vehicle. On gestation day 20, all dams were subjected to Caesarean section under surgical anesthesia.

Examinations

Maternal examinations:
Body weights were recorded on days 0, 6, 11, 15 and 20 of gestation. All animals were observed daily for appearance and behavior with particular attention to food consumption and weight.
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes, examinations included: number of corpora lutea, implantation sites, resorption sites and survival (live and dead fetuses)
Fetal examinations:
- External examinations: Yes, all per litter were examined grossly for the presence of external congenital abnormalities
- Soft tissue examinations: Yes, one-third of the fetuses of each litter underwent detailed visceral examinations employing the Wilson technique
- Skeletal examinations: Yes, the remaining two-thirds were cleared in potassium hydroxide, stained with alizarin red S dye and examined for skeletal defects.


Statistics:
No data
Indices:
Sex, numbers of corpora lutea, implantation sites, resorption sites, live and dead fetuses
Historical control data:
No data

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
not specified
Description (incidence and severity):
Results not further specified
Dermal irritation (if dermal study):
not examined
Mortality:
no mortality observed
Description (incidence):
No mortality occurred
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No effects on body weight were observed in comparison to the untreated control
Food consumption and compound intake (if feeding study):
not specified
Description (incidence and severity):
Results not further specified
Food efficiency:
not examined
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 examined
Gross pathological findings:
no effects observed
Description (incidence and severity):
No adverse effects observed during gross necrosy in comparison to the untreated control
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Details on results:
The administration of up to 310 mg/kg bw/day of the test material to pregnant rats for 10 consecutive days had no clearly discernible effect on maternal survival.

Maternal developmental toxicity

Number of abortions:
no effects observed
Description (incidence and severity):
No abortion occured in any pregnant female rat.
Pre- and post-implantation loss:
not examined
Total litter losses by resorption:
no effects observed
Description (incidence and severity):
There were no notable effects on resorptions after dosing with potassium chloride when compared with the controls.
Early or late resorptions:
not examined
Dead fetuses:
no effects observed
Description (incidence and severity):
There were no notable effects on dead fetuses after dosing with potassium chloride when compared with the controls.
Changes in pregnancy duration:
not specified
Changes in number of pregnant:
no effects observed
Description (incidence and severity):
There were no notable effects on the number of pregant females after dosing with potassium chloride when compared with the controls.
Other effects:
no effects observed
Description (incidence and severity):
There were no notable effects on the number of corpora lutea after dosing with potassium chloride when compared with the controls.
Details on maternal toxic effects:
The administration of up to 310 mg/kg bw of the test material to pregnant rats for 10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival.

Effect levels (maternal animals)

Key result
Dose descriptor:
NOAEL
Effect level:
> 310 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: no adverse effects observed at the highest dose tested

Maternal abnormalities

Abnormalities:
no effects observed

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
There were no notable effects on fetal body weight after dosing with potassium chloride when compared with the controls.
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
There were no notable effects on live fetuses after dosing with potassium chloride when compared with the controls.
Changes in sex ratio:
no effects observed
Description (incidence and severity):
There were no notable effects on sex ratio after dosing with potassium chloride when compared with the controls.
Changes in litter size and weights:
no effects observed
Description (incidence and severity):
There were no notable effects on litter size after dosing with potassium chloride when compared with the controls.
Changes in postnatal survival:
not examined
External malformations:
no effects observed
Description (incidence and severity):
There were no notable effects on external malformations after dosing with potassium chloride when compared with the controls.
Skeletal malformations:
no effects observed
Description (incidence and severity):
There were no notable effects on skelatal malformations after dosing with potassium chloride when compared with the controls.
Visceral malformations:
no effects observed
Description (incidence and severity):
There were no notable effects on visceral malformations after dosing with potassium chloride when compared with the controls.
Other effects:
not specified
Details on embryotoxic / teratogenic effects:
The administration of up to 310 mg/kg bw of the test material to pregnant rats for 10 consecutive days had no clearly discernible effect on fetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occuring spontaneously in the sham-treated controls.

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
> 310 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no adverse effects observed at the highest dose tested

Fetal abnormalities

Abnormalities:
no effects observed

Overall developmental toxicity

Developmental effects observed:
no

Applicant's summary and conclusion

Conclusions:
In this study conducted similar to OECD Guideline 414, oral administration of potassium chloride given once a day to Wistar rat dams from Day 6 to 15 of gestation was well tolerated of up to 310 mg/kg bw/day. As no adverse results were observed in any examined parameter, the NOAEL for reproductive/developmental and maternal toxicity is considered to be greater than 310 mg/kg bw/day.
Executive summary:

In a developmental toxicity study performed similar to OECD 414, potassium chloride was administered to groups of 20-23 pregnant adult female Wistar rats/dose by gavage at dose levels of 0, 3.1, 14.4, 66.8 and 310.0 mg/kg bw/day from day 6 through day 15 of gestation. The animals were sacrificed on gestation day 20.

No treatment-related effects were seen in maternal or offspring survival. Regarding maternal toxicity, no effects were seen in the total number of corpora lutea, implant sites, resorptions, soft tissue observations or live foetuses. Regarding the foetuses, no effects were noticed in sex ratio and average foetus weight. In addition, no differences were seen in either soft or skeletal examinations. As no adverse results were observed in any examined parameter, the NOAEL for reproductive/developmental and maternal toxicity is considered to be greater than 310 mg/kg bw/day.

The developmental toxicity study in the rat is classified acceptable and satisfies the guideline requirement for a developmental toxicity study (according to OECD 414) in rats.