Registration Dossier

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Information taken from secondary literature.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1995
Reference Type:
study report
Title:
Unnamed
Year:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
not specified
Qualifier:
according to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
Version / remarks:
(The scope of the histopathological examination complied with this guideline)
Deviations:
not specified
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Potassium tetrafluoroborate
- Analytical purity: 100.1% pure
No further information on the test material was stated.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: average initial weights of the males: 133.7 to 137.4 g, and females: 124.9 to 129.0 g.
No further information on the test animals was stated.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
(deionised water)
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS:
- The rats received potassium tetrafluoroborate as a solution in deionised water.
No further information on the oral exposure was stated.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
28 days (plus a recovery period of 14 days for the the satelitte control and high dose groups)
Frequency of treatment:
No data
Doses / concentrations
Remarks:
Doses / Concentrations:
20, 80 and 320 mg/kg body weight
Basis:
other: actual dose received
No. of animals per sex per dose:
- Main groups: 5 males/5 females
- Satellite groups: 5 males/5 females
- Recovery groups: 5 males/5 females (control and high dose)
Control animals:
yes, concurrent vehicle
Details on study design:
DOSE-FINDING STUDY:
- Goups of 5 male and 5 female Wistar rats were treated by oral gavage with potassium tetrafluoroborate (99.4% pure).
- Animals received doses of 0 (controls), 50, 157 and 500 mg/kg bw in polyethylene glycol 400 on 5 consecutive days.
- No clinical signs of toxicity were seen.
- Body weight development of the high dose animals was slightly, but not statistically significantly less than that of the control group.
- Absolute liver weights were reduced in high dose males and in the females receiving doses of and above 157 mg/kg body weight.
- Absolute testicular weights in the 500 mg/kg group were lower than controls.
- Absolute and relative ovary weights were increased from 157 mg/kg body weight.
- Upon necropsy, 9/10 high dose animals showed signs of gastric mucosal corrosion (pale or slightly reddish erosions, detachable whitish coating).

MAIN STUDY (28-day study):
- The study included satellite groups of 5 males and 5 females per dose group for interim sacrifice after 8 days.
- Another 5 males and 5 females in the control and the high dose groups were maintained for a 14-day recovery period.
Positive control:
No data

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Cage side observations checked: mortality, behaviour and clinical picture

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes

FOOD CONSUMPTION: Yes

FOOD EFFICIENCY: No data

WATER CONSUMPTION: Yes

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Parameters examined: erythrocyte count, haematocrit value, haemoglobin value and mean corpuscular volume.

CLINICAL CHEMISTRY: Yes
- Parameters examined: thyroid hormone levels: thyroxin, triiodothyronine and thyriod-stimulating hormone.
- Time schedule for collection of blood: at days 8 and 28 as well as at the end of the recovery period.
- How many animals: in all groups.

URINALYSIS: Yes

NEUROBEHAVIOURAL EXAMINATION: No

No further information on the observations and examiniations performed and frequency was stated.
Sacrifice and pathology:
GROSS PATHOLOGY: YES
- Organ weights were measured.
- Gross pathology of the organs, including the thyroid and parathyroid glands, was conducted.

HISTOPATHOLOGY: Yes
- The scope of examinations complied with OECD guidelaine 408.
- The thyriod and parathyroid glands from all dose goups were examined by light microscopy.
No further information on the sacrifice and pathology was stated.
Other examinations:
No data
Statistics:
No data

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
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):
no effects observed
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY
- There were no deaths during the study.
- Behaviour and clinical picture of animals remained unaffected.

BODY WEIGHT AND WEIGHT GAIN
- Body weight development remained unaffected.

FOOD CONSUMPTION
- Food consumption remained unaffected.

WATER CONSUMPTION
- Water consumption remained unaffected.

HAEMATOLOGY
- A slight, but statistically significant reduction in erythrocyte count and haematocrit value was seen in the females of the mid and high dose groups.
- In the high dose females, decreased haemoglobin values were noted.
- The values obtained for mean corpuscular volume were not affected.
- By the end of the 14-day recovery period, the haematological parameters had returned to control values.

CLINICAL CHEMISTRY
- Clinical chemistry parameters revealed no treatment-related effects.
- There were no treatment-related alterations in thyroid hormone levels.

URINALYSIS
- Urinalysis parameters revealed no treatment-related effects.

ORGAN WEIGHTS
- No changes in organ weights were observed.

GROSS PATHOLOGY
- Gross pathology examination of the organs, including the thyroid and parathyroid glands, were without findings.

HISTOPATHOLOGY: NON-NEOPLASTIC
- Histopathological examination of the organs, including the thyroid and parathyroid glands, were without findings.

No further details on results given.

Effect levels

open allclose all
Dose descriptor:
NOEL
Effect level:
> 320 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: No evidence of systemic effects.
Dose descriptor:
NOEL
Effect level:
20 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: NOEL based on alterations in haematological parameters at 80 and 320 mg/kg bw/d.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The no observed effect level (NOEL) for male rats can be expected above the high dose level of 320 mg/kg bw/d, while it was established at 20 mg/kg bw/d for female rats based on alterations in haematological parameters at 80 and 320 mg/kg bw/d.