Barium titanium trioxide

Endpoint summary

Description of key information

Acute oral toxicity
in vivo, rat: LD50 > 12000 mg/kg bw (non GLP, no guideline, Brown & Mastromatteo, 1962)
Acute inhalation toxicity
in vivo, rat: LC50 > 4.89 mg/L air (GLP, OECD 403, TÜV SÜD PSB, 2012)
Acute dermal toxicity
in vivo, rat: LD50 > 2000 mg/kg bw (GLP, OECD 402, TÜV SÜD PSB, 2012)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1962

Reliability:

2 (reliable with restrictions)

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Known dry weights of titanates were mixed with corn oil to form a 40% suspension. This was diluted for use as required in order that each animal should receive the same total volume in proportion to its body weight.

GLP compliance:

no

Test type:

acute toxic class method

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

Young adult male Wistar rats weighing 200 grams or more were used. They were obtained from a commercial breeder. The animals were housed in seperate wire cages and supplied with water and a standard fox cube diet at libitium.

Route of administration:

oral: gavage

Vehicle:

other: corn oil

Details on oral exposure:

Because of the insolubiltiy of the titanates, corn oil was used as a vehicle for adminstration. Known dry weights of titanates were mixed with corn oil to form a 40% suspension. This was diluted for use as required in order that each animal should receive the same total volume in proportion to its body weight. For the determination of acute oral toxicity the sample was adminstered directly into the stomach in calculated amounts using a rubber catheder stomach tube and a graduated syringe.

Doses:

Dose levels:
1.5 g/kg bw
3.0 g/kg bw
6.0 g/kg bw
12.0 g/kg bw

No. of animals per sex per dose:

6 male animals per dose

Control animals:

yes

Details on study design:

All animales were maintend and observed for one month following observation of test materials. The time of death and any evidence of toxic effect were noted. The same amount of corn oil alone were given to a similar number of rats in each case of control.
Rats that died as a result of the adminstation of titantate were examined for evidence of toxic effects. Gross findings doses were first carried out by both oral and intraperitonal LD50 doses with their 95% fiducial limits, groups of six animal were given four dose level which varied by a constant geometric factor. those dose levels were based on the range finding data. The LD50 dose was calculated according to the tables and instructions given by Weil

Sex:

male

Dose descriptor:

LD0

Effect level:

1 500 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

LD0

Effect level:

3 000 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

LD0

Effect level:

6 000 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

LD0

Effect level:

12 000 mg/kg bw

Based on:

test mat.

Mortality:

All animales were maintend and observed for one month following observation of test materials. The time of death and any evidence of toxic effect were noted. Rats that died as a result of the adminstation of titantate were examined for evidence of toxic effects.
None of the rats died as a result of oral adminstration despite quite high dosage rates.

Clinical signs:

other: At the higher dosage levels with both routes of administration the rats were lethargic for the first few hours. Other findings on the high dosage levels were: reduced activity, temporary loss of appetite, and brownish colored discharge from the nose and e

Gross pathology:

Histologic study showed no specific changes .
There was evidence of inflammatory change in the liver, kidney, spleen, and lungs. There were also hemorrhagic areas noted in the kidneys

Table II	Acute Oral Toxicity Ratio of Rats killed those treated at graduated dose levels (grams of titanate compound per kilogram of body weigth)
Compound	Dose Level (gms/kg)
	1,5	3,0	6,0	12,0
Barium Titanate	0/6	0/6	0/6	0/6

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 >5000 mg/kg bw. Hence, barium titanate need not be classified according to GHS.

Executive summary:

The minimal lethal doses by the oral route exceeds 12g/kg in the rat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

12 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guidline study

Justification for type of information:

Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: National University of Singapore, Centre for Animal Resources (CARE), Singapore
- Age at study initiation: 10 - 12 weeks old
- Weight at study initiation: males: 366 - 386 g; females: 258 - 288 g
- Housing: OptiMICE Caging IVC Systems for Rats
- Diet (e.g. ad libitum): Altromin Maintenance Diet #1324
- Water (e.g. ad libitum): Tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 22
- Humidity (%): 30 - 70

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The dust cake of the test substance was prepared on the administration day using a hydraulic press at the presssure of 3 tons on 1'/4" DIE.
- Exposure apparatus: TSE Nose (head) only Inhalation Exposure System
- Rate of air: Flow air (L/min) = 15.00; Flow application (L/min) = 15.00; Flow sampling (L/min) = 1.00
- Measurement of actual concentration: Gravimetry method through a filtration unit connected to one of the exposure port.
- Temperature, humidity, in air chamber: A sensor is connected to one of the exposure port.
- Dust generator speed, U/min: 34.008 U/min (maximum)
- Dust generator support / feed, mm/min: 3.418 mm/min (maximum)

TEST ATMOSPHERE
- Particle size distribution: Cascade impactor 0.5 L/min

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: According to OECD 436, the limit dose is 5 mg/L. Based on the technical pre-test of the test item, the maximum attainable dose level was 4.35 mg/L.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Measurement 1: 4.63 mg /L
Measurement 2: 4.75 mg /L
Measurement 3: 5.29 mg /L
Average: 4.89 mg /L

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Adverse effects were observed on each animal twice on the exposure day, and daily up to 14 days. Body weight of each animal was measured on Day 1, 3 and 7.
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LC50

Effect level:

4.89 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: maximum attainable concentration

Mortality:

No animal was found dead prior to endpoint day.

Clinical signs:

other: No adverse effect was observed throughout the observation period.

Body weight:

Body weight changes were in the normal range.

Gross pathology:

No necropsy finding.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the above results, exposing the test item- barium titanate milled ABT-O-21, to rats for 4 hours using TSE Nose (head) only Exposure System, no acute inhalation toxicity was observed on the test system at the maximum attainable concentration of 4.89 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

4 890 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 Apr 2012 - 16 May 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study according to OECD guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: National University of Singapore, Centre for Animal Resources (CARE), 7 Perahu Road, Singapore 718836
- Age at study initiation: 7 to 9 weeks old
- Weight at study initiation: male animals: 266 - 310 g, female animals: 220 - 272 g
- Housing: OptiMICE Caging Systems for rats
- Diet (e.g. ad libitum): Altromin Maintenance Diet #1324; throughout dosing and observation period
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 22
- Humidity (%): 30 - 70

Type of coverage:

occlusive

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 10 percent of the total surface area

REMOVAL OF TEST SUBSTANCE
- Washing: water

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The observation of adverse effects was conducted on each animal during the first 30 minutes, periodically during the first 24 hours (with special attention during the first 4 hours), and periodically thereafter. The body weight of each animal was measured every 7 days.
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no adverse effects observed

Mortality:

No animal died during dosing and observation period.

Clinical signs:

other: No adverse effect was observed on all the other test animals during observation period.

Gross pathology:

Necropsy was conducted on all the test animals on the termination day. No abnormality was observed
on all the test animals.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Hence, based on CLP for acute toxicity hazard categories, thesubstance does not require classification for acute dermal toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

There are reliable studies available to assess the potential of the test substance for acute toxicity.

Acute oral toxicity

In a non guideline acute toxic class method study the acute oral toxicity potential of the test substance barium titanium trioxide was assessed in 6 male Wistar rats per dose (Brown & Mastromatteo, 1962). Dose levels from 1500 to 12000 mg/kg bw were administered by gavage. The animals were maintained and observed for one month. None of the rats died as a result of oral administration despite quite high dosage rates. At the higher dosage levels rats showed lethargy for the first few hours. Other findings on the high dosage levels were reduced activity, temporary loss of appetite, and brownish coloured discharge from the nose and eyes. At the end of the month rats appeared normal again.

Therefore, under the test conditions chosen the test item barium titanium trioxide does not show acute oral toxicity in rats.

Acute inhalation toxicity

In order to assess the acute inhalation toxicity potential of the test substance barium titanium trioxide (purity: > 99 weight-%), the test in Wistar rats was performed according to the method described in OECD guideline 403 (TÜV SÜD PSB, 2012). Based on the technical pre-test of the test item, the maximum attainable dose level was 4.35 mg/L. The limit dose is normally used for test substances for which the toxicity or mortality is not expected. Thus, limit dose of 5 mg /L was selected based on the information provided by the sponsor and the technical pre-test of the test item.

The animals were exposed to barium titanium trioxide using TSE Nose (head) only Inhalation Exposure System for 4 hours. The actual maximum attainable concentrations of the test substance were 4.63, 4.75 and 5.29 mg/L. Therefore the average maximum attainable concentration of the test substance is 4.89 mg/L.

No animal was found dead and no adverse effect was observed throughout the study and the observation period. Necropsy finding was normal in all test animals.

Hence,under the test conditions chosen exposing the test item barium titanium trioxide to rats for 4 hours using TSE Nose (head) only Exposure System, no acute inhalation toxicity was observed at the maximum attainable concentration of 4.89 mg/L.

Acute dermal toxicity

In order to assess the acute dermal toxicity potential of the test substance barium titanium trioxide (purity: > 99 weight-%), the acute dermal toxicity test in Wistar rats was performed according to the method described in OECD guideline 402 (TÜV SÜD PSB, 2012). The test substance was moistened with water for injection and administered by topical application on the shaved area of each animal. A single dose of 2000 mg/kg bw of the test substance was administered once to 5 animals per sex. The test item was then held in contact with the skin using a gauze patch and occlusive dressing. The exposure was conducted for 24 hours. At the end of exposure period, residual test item was removed and cleaned carefully with water.The observation of adverse effects was conducted up to 14 days.

No animal died during dosing and observation period and no adverse effect or abnormality was observed in all test animals.

Based on the results above the test substance barium titanium trioxide does not show an acute dermal toxicity under the test conditions chosen.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008:

Based on the results, the classification of the test substance for acute toxicity under Regulation 1272/2008 is not warranted.