barium(2+); oxygen(2-); titanium(4+); zirconium(4+) ;calcium (2+)

Endpoint summary

Description of key information

read-across substance barium titanium trioxide:

- 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:

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 eyes.
Rats that survived appeared normal at the end of one month.

Body weight:

Young adult male Wistar rats weighing 200 grams or more were used.
Body weight in the treated group after one month was the same as that for control animals.

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:

GHS criteria not met

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

4 890 mg/m³

Acute toxicity: via dermal route

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.