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Acute Toxicity: inhalation

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acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
7 January 1992 to 24 September 1992
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.
Justification for type of information:
According to Column 2 of Section 8.5 of Annex VIII details specific rules for adaptation, notably requiring information on at least one other route of exposure depending on the nature of the substance and the likely route of human exposure.
Considering the chemico-physical characteristics of the substance and the likely route of human exposure, it was judged as priority and essential to submit information related to acute toxicity by inhalation route.

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
according to guideline
EPA OTS 798.1150 (Acute inhalation toxicity)
Version / remarks:
GLP compliance:
Test type:
standard acute method
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Potassium hexatitanate
Details on test material:
- Physical form of substance: fibre.

- Lot/batch No.: A-1606, A-1Y06.

- Storage condition of test material: stored at room temperature and humidity conditions, out of direct contact with light.

Test animals

Fischer 344
Details on test animals or test system and environmental conditions:
- Source: Charles River Laboratory.

- Age at study initiation: 5 - 7-week old.

- Weight at study initiation: 71.9 - 86.2 g (males), 71.0 - 82.2 g (females).

- Fasting period before study: Not reported (food withheld during the 4-hour exposure period).

- Housing: The animals were individually housed in stainless steel wire cages.

- Diet: Purina Certified Rodent Chow (pellets) ad libitum.

- Water: Water from the City of Columbus municipal supply and was not further treated at the testing facility. Ad libitum.

- Acclimation period: 7 days.

- Temperature (°C): 19 - 22°C

- Humidity (%): 47 - 73%.

- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark each day.

IN-LIFE DATES: From: Day 1 To: Day 15.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
other: breathing zone
Details on inhalation exposure:
- Exposure chamber volume: 0.5 m3.

- Source and rate of air: Approximately 500 liters per minute, airflow rate through the plenum.

- System of generating particulates/aerosols: Aerosol generator consist of two-part system.

- Method of particle size determination: Scanning Electron Microscopy (SEM).

- Temperature, humidity, pressure in air chamber: See 'details on test animals and environmental conditions'.

- Brief description of analytical method used:Concentration was monitored by gravimetric technique. The.test atmosphere temperature and humidity were monitored in the exposure chamber during the
actual exposure. Chamber concentration uniformity was determined by gravimetric concentration sampling on the horizontal plane of the chamber where the animals were exposed.

- Samples taken from breathing zone: No

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Mean fiber lengths of 20, 18, 21, and 11 μm for the plenum bottom, middle, top and exposure chamber, respectively. The mean fiber width for each location was 6.5, 6,0, 7.2, and 4.2 μm for the plenum bottom, middle, top and exposure chamber, respectively.

- MMAD (Mass median aerodynamic diameter for liq.+solid aerosol):
1st sample: mean fibre length = 16.2 µm
mean fibre width = 7.4 µm
2nd sample: mean fibre length = 14.5 µm
mean fibre width = 7.6 µm

Analytical verification of test atmosphere concentrations:
Duration of exposure:
4 h
1.9 mg/L.
No. of animals per sex per dose:
5 per sex.
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
Mortality & clinical observations: Twice daily.
Body weight: On Days 1, 8 and 15.

- Necropsy of survivors performed: yes, on Day 15.
In-life and postmortem data (necropsy findings) were collected using the Xybion® Path/Tox System, (Xybion Medical Systems Corporation, Cedar Knolls, NJ) for body weights, daily clinical observations, and gross findings.
Individual animal body weight data was collected weekly and summarized by sex. Data were not analyzed statistically since there were no group to group comparisons.

Results and discussion

Preliminary study:
Chamber uniformity measurements were completed during the pre-study validation of the inhalation system. The data show that the variability, as defined by the Relative Standard Deviation of all samples, was less than 2.5%. The mean concentration was 1.94 mg/L, which was 97% of the 2.0 mg/L target value. This pre-study analysis showed a uniform distribution of the atmosphere within the chamber.
Effect levels
Dose descriptor:
Effect level:
> 1.9 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Male: 1.9 mg/L; Number of animals: 5; Number of deaths: 0
Female: 1.9 mg/L; Number of animals: 5; Number of deaths: 0
Clinical signs:
other: Signs of toxicity related to dose levels: Clinical signs of nasal discharge, ocular discharge and ruffled fur occurred after exposure and persisted for several days. There were no other visible effects.
Body weight:
Animals gained weight at a rate consistent with that expected of this age and strain of rat.
Gross pathology:
Effects on organs: Necropsy findings revealed no gross lesions or abnormalities of any kind.
Other findings:
Not reported.

Applicant's summary and conclusion

Interpretation of results:
other: classified for STOT-SE Category 3 / R37 - irritating to respiratory system
Criteria used for interpretation of results: EU
Under the conditions of the study, the LD50 of the test material was determined to be > 1.9 mg/L air (4h): the substance is not classified for acute toxicity by inhalation in accordance to CLP criteria.
Executive summary:

Under the conditions of the study, the LD50 of the test material was determined to be > 1.9 mg/L air (4h): the substance is not classified for acute toxicity by inhalation in accordance to CLP criteria.