Borate(1-), bis[ethanedioato(2-)-.kappa.O1,.kappa.O2]-, potassium (1:1), (T-4)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009-08-17 to 2010-02-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

, October 2008

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

, April 29, 2004

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

, December, 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

244761-29-3

EC Number:

607-383-9

Cas Number:

244761-29-3

IUPAC Name:

244761-29-3

Constituent 2

Reference substance name:

Lithium bis(oxalato)borate

EC Number:

456-990-3

EC Name:

Lithium bis(oxalato)borate

IUPAC Name:

lithium bis(oxalato)borate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

SMILES: O=C1O[B-]2(OC1=O)OC(=O)C(=O)O2.[Li+]

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (Europe) Laboratories Inc. TOXI COOP Ltd. 1103 Budapest, Cserkesz u. 90
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 203-229 g
- Fasting period before study: food but not water was withheld for 24h before treatment
- Housing: 1 animal/cage (Type II. polypropylene/polycarbonate)
- Diet (e.g. ad libitum): ssniff SM R/M-Z+H, ad libitum
- Water (e.g. ad libitum): tap water from municipal supply, ad libitum
- Acclimation period: at least 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.4-24.7
- Humidity (%): 38-67%
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 17.5, 55, 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Lot/batch no. (if required): 058K0070

Doses:

175, 550, 2000 mg/kg bw

No. of animals per sex per dose:

treatment group 1 (175 mg/kg bw): 2 females
treatment group 2 (550 mg/kg bw): 4 females
treatment group 3 (2000 mg/kg bw): 1 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were done daily
- Necropsy of survivors performed: yes
- clinical signs: were observed 30 min, 1, 2, 3, 4 and 6 hours after treatment and once each day for 14 days thereafter
- body weight: were recorded on days -1, 0 (day of experiment), and on days 7 and 14

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

550 mg/kg bw

Based on:

test mat.

95% CL:

88.94 - 2 430

Effect levels 2

Sex:

female

Dose descriptor:

LD0

Effect level:

175 mg/kg bw

Based on:

test mat.

Mortality:

Treatment group 1: 175 mg/kg bw
No mortality occurred in this group.

Treatment group 2: 550 mg/kg bw
Treatment with lithium bis(oxalato)borate (LiBOB) at a dose level of 550 mg/kg bw caused mortality in case of 2 animals (2/3).
One female died died shortly after treatment due to a dosing accident (misgavage) and/or gastro-esophageal reflux (not test item related).

Treatment group 3: 2000 mg/kg bw
Treatment with lithium bis(oxalato)borate (LiBOB) at a dose level of 2000 mg/kg bw caused mortality in this dose group.

Clinical signs:

other: In Treatment group 1 LiBOB caused decreased activity in one out of two rats. In Treatment group 2 a decreased activity in one out of 4 rats was observed.

Gross pathology:

Treatment group 1: 175 mg/kg bw
Treatment with lithium bis(oxalato)borate (LiBOB) at a dose level of 175 mg/kg bw caused dilatation, (pelvis, right) and white cloudy fluid in one rat’s kidneys in this dose group.

Treatment group 2: 550 mg/kg bw
Treatment with lithium bis(oxalato)borate (LiBOB) at a dose level of 550 mg/kg bw caused diffuse dark red discoloration of the lungs and liver, dark, punctuate red discoloration of the thymus (bilateral) and dark, red, diffuse discoloration and mucosa in ileum in this dose group.

Treatment group 3: 2000 mg/kg bw
Treatment with lithium bis(oxalato)borate (LiBOB) at a dose level of 2000 mg/kg bw caused diffuse dark red discoloration of the liver and dark, red, diffuse discoloration and mucosa in ileum, duodenum and jejunum in this dose group.

Any other information on results incl. tables

Read across for evaluation of acute toxicity of potassium bis(oxalato)borate from the acute toxicity (oral) study results of lithium bis(oxalato)borate is justified on the basis of structural similarity of the substances. The bis(oxalato)borate salt part [B(C2O4)2] is the same in both substances and only the cationic part of salts differ (lithium or potassium). Both lithium and potassium belong to alkali-metals.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Lithium bis(oxalato)borate (LiBOB) was ranked into Category 4 of Globally Harmonized Classification System as the estimated LD50 is between 300 and 2000 mg/kg bw. Based on structural similarity, the result can be used for read across when evaluating acute toxicity of potassium bis(oxalato)borate. For risk assessment and classification, also potassium bis(oxalato)borate can be ranked into Category 4 of Globally Harmonized Classification System. See also attachment in section 13 (Analogue approach justification).

Executive summary:

An acute oral toxicity study (up-and-down procedure) was performed with lithium bis(oxalato)borate (LiBOB) according to OECD Guideline 425. 7 young female CRL:(WI) BR Wistar rats were treated with the test item by oral gavage at dose levels of 175, 550 and 2000 mg/kg bw in corn oil. The concentrations of the formulations in corn oil were 200, 55 and 17.5 mg/mL with a constant treatment volume of 10 mL/kg bw.

Lithium bis(oxalato)borate (LiBOB) caused 100% mortality at 2000 mg/kg bw (1/1 animal) and 67% (2/3 animals) mortality at 550 mg/kg bw. There was no mortality at 175 mg/kg bw.

Treatment with lithium bis(oxalato)borate (LiBOB) caused mortality at a dose level of 2000 mg/kg bw, decreased activity (1/3) and mortality (2/3) at 550 mg/kg bw and decreased activity (1/2) at 175 mg/kg bw.

The body weight gain of the animals was considered to be normal with no indication of test item related effect.

The macroscopic examination revealed some minor alterations including diffuse dark red discoloration of the lungs (1/6) and liver (3/6), dark, punctuate red discoloration of the thymus (bilateral) (1/6), dark, red, discoloration, diffuse, mucosa in ileum (2/6), duodenum, jejunum (1/6). Dilatation, (pelvis, right) and white cloudy fluid was found in one rat’s kidneys.

The study was marked reliable without restrictions and LD50 and LD0 values of 550 and 175 mg/kg bw respectively were derived. (LAB, 2010).

Based on structural similarity, the result can be used for read across and classification of potassium bis(oxalato)borate.