Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30th Novemebr 2017 - 27th December 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Lewer Corporation Batch Number: 20170425
- Expiration date of the lot/batch: 24th April 2019
- Purity test date: 97.6%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: 15 to 25° C, protected from light.
- Stability under test conditions: Stable
- Solubility and stability of the test substance in the solvent/vehicle: Test item administered as a dispersion (see below), test item stable in the vehicle.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: not applicable
- Preliminary purification step (if any): not applicable
- Final preparation of a solid: Test item dispersed in 1% w/v methylcellulose.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd Margate, Kent
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 210 - 222g
- Fasting period before study: overnight
- Housing:In compliance with ‘Code of Practice for the Housing and Care of Animals Bred, Supplied or Used for Scientific Purposes ‘ (Home Office, London, 2014)
- Diet: ad libitum with the exception of the fasting period.
- Water: ad libitum
- Acclimation period: 6 - 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):20 - 24
- Humidity (%):45 - 65
- Air changes (per hr):15 - 20
- Photoperiod (hrs dark / hrs light):12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Doses:
Sighting study performed using single doses at 50 mg/kg and 300 mg/kg.
Based on the results of the sighting study a further 4 animals were dosed at 300 mg/kg.
No. of animals per sex per dose:
1 female animal at 50 mg/kg
5 female animals at 300 mg/kg.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs were recorded 15 and 30 minutes post teatment, hourly between 1 and 4 hours, twice daily on days 2,3 and 4 and once daily from 5th day to the end of the observation period. Body weights were recorded on days 1,4,8 and 15 post treatment.
- Necropsy of survivors performed: Yes
- Other examinations performed: Not applicable

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 quoted from the CLP Regulation Section 3.1.3.6.2.3, on the basis of the classification being determined as Acute Tox 4 from the study results.
Mortality:
50 mg/kg - 0/1
300 mg/kg - 1/5 (Day 2)
Clinical signs:
50 mg/kg: No clinical signs observed.
300 mg/kg - hunched posture, piloerection, ataxia, deceased activity, pallor of the extremities and ptosis. The clinical signs developed from 2 hours after dosing up to day 7.
Body weight:
All surviving animals showed either no change or a decrease in body weights over the first week of the observation period, followed by a gain in body weight during the second week of observation.
Gross pathology:
Animals that died during the study - No macroscopic changes
Surviving animals - One animal out of the four survivng showed pelvic dilation of the kidney.

Any other information on results incl. tables

See attached document below for results tables.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The results of the fixed dose oral toxicity study on barium selenate conclude the requirement to classify the test substance as Acute Toxicity Category 4 according to the Globally Harmonised System of Classification of Chemicals.
Executive summary:

A GLP study was performed to assess the toxicity of Barium Selenate when administered orally. The study was performed in accordance with OECD guideline 420 following a fixed dose procedure.  Initially single female rats were dosed at 50 mg/kg bw/day and 300 mg/kg bw/day. No mortality or signs of toxicity were observed at 50 mg/kg bw/day; therefore a further 4 female animals were dosed at 300 mg/kg bw/day.

 The animals were observed for 14 days after dosing. All animals were subject to a gross pathological examination.

One animal died after dosing with 300 mg/kg bw/day on day 2. No clinical signs were observed in animals dosed with 50 mg/kg bw/day, animals dosed with 300 mg/kg bw/day exhibited hunched posture, piloerection, ataxia, deceased activity, pallor of the extremities and ptosis. The clinical signs developed from 2 hours after dosing up to day 7.

All surviving animals showed either no change or a decrease in body weights over the first week of the observation period, followed by a gain in body weight during the second week of observation.

No macroscopic changes were observed in the animal that died during the study, one of the surviving 4 animals dosed with 300 mg/kg bw/day showed pelvic dilation of the kidney.

Based on the results of the study, the test substance barium selenate is classified as Acute Toxicity Category 4 according to the Globally Harmonised System of Classification of Chemicals.