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Toxicological information

Acute Toxicity: inhalation

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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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
fixed concentration procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: nanomaterial
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

- Name of test material (as cited in study report): coated fine particle titanium dioxide
- Substance type: white powder
- Lot/batch No.: NP 89/118
- Storage condition of test material: stored in the dark at ambient temperature
No further details are given.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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% and 56% by weight respectively for NP 89/117 and NP 89/118.
- MMAD: 7.0 µm and 3.2 µm for NP 89/117 and NP 89/118, respectively.

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)
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

Results and discussion

Preliminary study:
no data
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
5.09 mg/L air
Exp. duration:
4 h
Remarks on result:
other: NP 89/117
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:
No adverse clinical signs were observed as a result of exposure to either NP 89/117 or NP 89/118.
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.
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.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information at tested dose levels Criteria used for interpretation of results: EU
Conclusions:
The Titanium Dioxide Powders, NP 89/117 and NP 89/118 were considered to be non-toxic to rats by the inhalation route at measured atmospheric concentrations of 5.09 and 3.43 mg/l respectively.