Lead bis(tetrafluoroborate)

Repeated dose toxicity: oral

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

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1995

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study 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

Test material information

Constituent 1

Reference substance name:

Potassium tetrafluoroborate

EC Number:

237-928-2

EC Name:

Potassium tetrafluoroborate

Cas Number:

14075-53-7

IUPAC Name:

potassium tetrafluoroborate

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 or test system 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

1

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.

2

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.