Titanium dioxide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions: - GLP is not compulsory at the time of conduct - Purity and stability of test items are missing

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions: - GLP is not compulsory at the time of conduct - Purity and stability of test items are missing

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Test type:

fixed concentration procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent, England
- Weight at study initiation: 104-127 g
- Housing: The rats were housed in a semi-barrier maintained animal room. Rats were housed 1 or 2 males or females per cage in suspended polypropylene cages with detachable stainless steel tops and bottoms. All cages were suspended over trays containing absorbent paper.
- Diet: ad libitum, except during the 4 hours exposure period; Rat and House (Modified) No. 1 Diet SQC Expanded
- Water: ad libitum, except during the 4 hours exposure period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 2
- Humidity (%): 55
- Photoperiod. 12 hours dark/light cycle
No further details are given.

Route of administration:

inhalation

Type of inhalation exposure:

nose only

Vehicle:

other: air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The aluminium exposure chamber was cylindrical in cross section and had a volume of approximately 41.5 litres.
- System of generating particulates/aerosols: The test atmospheres were generated using an Aerostyle dust generator. Filtered, oil-free compressed air for the production of the test aerosol was supplied by Hydrovane compressors.
- Method of particle size determination: The particle size distribution of the dispersed material inside the exposure chamber was estimated twice during the exposure period using a Marple (Model 296) Cascade Impactor.
- Temperature, humidity, pressure in air chamber: During the exposure periods the temperature within the exposure chamber was measured by a mercury thermometer located at the animals' breathing zone whilst the relative humidity was monitored using wet/dry bulb mercury thermometers. The chamber temperature and relative humidity were measured at 30 min intervals throughout the exposure periods and ranged from 25-26°C and 19-35% respectively for temperature and humidity.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Particle size distribution measurements revealed that the percentage of particles <3.5 µm was 56% by weight for NP 89/118.
- MMAD: 3.2 µm for NP 89/118

No further details are given.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Chamber concentrations were measured gravimetrically at regular intervals during the exposure periods.

Duration of exposure:

4 h

Concentrations:

measured:
NP 89/118: 3.43 mg/l (MMD=3.2µm)

No. of animals per sex per dose:

groups of 5 males and 5 females

Control animals:

not specified

Details on study design:

During exposure the animals were observed at regular intervals for signs of any adverse reactions to treatment. On completion of the 4 hours exposure period, the animals were removed from the chamber, unloaded from the restraint tube, returned to their cages in the animal holding room and observed for clinical signs.
All the rats were observed for clinical signs at frequent intervals throughout the exposure period, for the first 1-2 hours post dosing and thereafter at least once daily during the subsequent 14 day observation period. The onset, intensity and duration of any signs observed were recorded.
All the rats were weighed immediately before dosing and on Days 2, 3, 4, 7, 10 and 14 post exposure.
At the end of the 14 day observation period all the animals were sacrificed and subjected to a macroscopic post mortem examination.

Statistics:

no data

Preliminary study:

no data

Sex:

male

Dose descriptor:

LC50

Effect level:

3.43 mg/L air

Exp. duration:

4 h

Remarks on result:

other: NP 89/118

Mortality:

There were no mortalities.

Clinical signs:

other: No adverse clinical signs were observed as a result of exposure to NP 89/118.

Body weight:

No adverse effect on body weight gain was observed.

Gross pathology:

Mottled lungs were recorded for 2/5 male and 3/5 female animals exposed to NP 89/118.

Other findings:

The lung body weight ratios for all the animals were considered to be within normal limits.

Interpretation of results:

GHS criteria not met

Conclusions:

The Titanium Dioxide Powder NP 89/118 was considered to be non-toxic to rats by the inhalation route at measured atmospheric concentrations of 3.43 mg/l air.

Executive summary:

McDonald, P. & Oshodi, R.O. (1989) exposed male and female rats to coated fine titanium dioxide according to OECD guideline 403. In a limit test, the rats were exposed nose only with 3.43 mg/L for 4 hours. Each group consisted of 5 female and 5 male rats. Gross pathological examination revealed mottled lungs for 2/5 male and 3/5 female animals in the coated fine group. However, no test item related toxicity, no body weight loss occurred after dosing, and no clinical signs were present during the conduct of the study. Hence, titanium dioxide powder was considered to be non-toxic to rats by the inhalation route at measured atmospheric concentrations of 3.43 mg/L.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Test type:

fixed concentration procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Titanium dioxide

EC Number:

236-675-5

EC Name:

Titanium dioxide

Cas Number:

13463-67-7

Molecular formula:

O2Ti

IUPAC Name:

dioxotitanium

Test material form:

solid: nanoform

Details on test material:

- Name of test material (as cited in study report): ultrafine titanium dioxide
- Substance type: white powder
- Lot/batch No.: NP 89/117
- Storage condition of test material: stored in the dark at ambient temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent, England
- Weight at study initiation: 104-127 g
- Housing: The rats were housed in a semi-barrier maintained animal room. Rats were housed 1 or 2 males or females per cage in suspended polypropylene cages with detachable stainless steel tops and bottoms. All cages were suspended over trays containing absorbent paper.
- Diet: ad libitum, except during the 4 hours exposure period; Rat and House (Modified) No. 1 Diet SQC Expanded
- Water: ad libitum, except during the 4 hours exposure period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 2
- Humidity (%): 55
- Photoperiod. 12 hours dark/light cycle
No further details are given.

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

nose only

Vehicle:

other: air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The aluminium exposure chamber was cylindrical in cross section and had a volume of approximately 41.5 litres.
- System of generating particulates/aerosols: The test atmospheres were generated using an Aerostyle dust generator. Filtered, oil-free compressed air for the production of the test aerosol was supplied by Hydrovane compressors.
- Method of particle size determination: The particle size distribution of the dispersed material inside the exposure chamber was estimated twice during the exposure period using a Marple (Model 296) Cascade Impactor.
- Temperature, humidity, pressure in air chamber: During the exposure periods the temperature within the exposure chamber was measured by a mercury thermometer located at the animals' breathing zone whilst the relative humidity was monitored using wet/dry bulb mercury thermometers. The chamber temperature and relative humidity were measured at 30 min intervals throughout the exposure periods and ranged from 25-26°C and 19-35% respectively for temperature and humidity.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Particle size distribution measurements revealed that the percentage of particles <3.5 µm was 20% by weight for NP 89/117
- MMAD: 7.0 µm for NP 89/117

No further details are given.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Chamber concentrations were measured gravimetrically at regular intervals during the exposure periods.

Duration of exposure:

4 h

Concentrations:

measured:
NP 89/117: 5.09 mg/l (MMD=7µm)

No. of animals per sex per dose:

groups of 5 males and 5 females

Control animals:

not specified

Details on study design:

During exposure the animals were observed at regular intervals for signs of any adverse reactions to treatment. On completion of the 4 hours exposure period, the animals were removed from the chamber, unloaded from the restraint tube, returned to their cages in the animal holding room and observed for clinical signs.
All the rats were observed for clinical signs at frequent intervals throughout the exposure period, for the first 1-2 hours post dosing and thereafter at least once daily during the subsequent 14 day observation period. The onset, intensity and duration of any signs observed were recorded.
All the rats were weighed immediately before dosing and on Days 2, 3, 4, 7, 10 and 14 post exposure.
At the end of the 14 day observation period all the animals were sacrificed and subjected to a macroscopic post mortem examination.

Statistics:

no data

Results and discussion

Preliminary study:

no data

Effect levels

Sex:

male

Dose descriptor:

LC50

Effect level:

5.09 mg/L air

Exp. duration:

4 h

Remarks on result:

other: NP 89/117

Mortality:

There were no mortalities.

Clinical signs:

other: No adverse clinical signs were observed as a result of exposure to NP 89/117

Body weight:

No adverse effect on body weight gain was observed.

Gross pathology:

Gross pathological examination revealed pale lungs for 3/5 male and 1/5 female animals exposed to NP 89/117.

Other findings:

The lung body weight ratios for all the animals were considered to be within normal limits.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The Titanium Dioxide Powder NP 89/117 was considered to be non-toxic to rats by the inhalation route at measured atmospheric concentrations of 5.09 mg/L air.

Executive summary:

McDonald, P. & Oshodi, R.O. (1989) exposed male and female rats to ultrafine titanium dioxide according to OECD guideline 403. In a limit test, the rats were exposed nose only with 5.09 mg/L for 4 hours. Each group consisted of 5 female and 5 male rats. Gross pathological examination revealed pale lungs in 3/5 male and 1/5 female animals in the ultrafine group. However, no test item related toxicity, no body weight loss occurred after dosing, and no clinical signs were present during the conduct of the study. Hence, titanium dioxide powder was considered to be non-toxic to rats by the inhalation route at measured atmospheric concentration of 5.09 mg/L.