Magnesium potassium titanium oxide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09-23 February 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study has been performed according to OECD and EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

(1997)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

436-900-9

EC Name:

-

Cas Number:

39290-90-9

Molecular formula:

Hill Empirical formula: K(0.2-0.7) Mg(0.4) Ti(1.6) O(3.7-3.95) CAS Empirical formula: K(0.2-0.7) Mg(0.4) Ti(1.6) O(3.7-3.95)

IUPAC Name:

Magnesium Potassium Titanium Oxide

Details on test material:

Batch: 0G99
White powder
Expiry date: 21 August 2001
Specific gravity: 3.38
Test substance storage: At room temperature in the dark
CAs number 275384-70-8 was given in the study report.

Test animals

Species:

rat

Strain:

other: Wistar, SPF-reared, Wistar derived (Crl:[WI]WU BR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS (5 males/5 females)
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: 6 weeks (before acclimatisation)
- Weight at study initiation: the mean body weights of the rats were 321 g and 200 g for male and female animals, resp., just before exposure.
- Earmark for identification
- Housing: Conventional conditions in suspended stainless steel cages fitted with wire-mesh floor and front
- Diet: a commercially available rodent diet (Rat & Mouse No. 3 Breeding Diet RM3) from SDS Special Diets Services, Witham, England).
- Water: Tap water suitable for human consumption.
- Acclimation period: 36 days
- No access to feed or water during exposure.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): between 19.0 and 22.0°C
- Humidity (%): between 40 and 66%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: none

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Exposure in a nose-only inhalation chamber, a modification of the chamber manufactured by ADG developments Ltd., Codicote, Hitchin, Herts. SG4 8 UB, United Kingdom. The inhalation chamber consisted of a cylindrical aluminium column, surrounded by a transparent cylinder. The column had a volume of ca. 50L and consisted of a top assembly with two mixing chambers, underneath a rodent tube section and the exhaust section at the bottom. The rodent tube section had 20 ports for animal exposure. Empty ports were closed if not used for test atmosphere sampling, particle size analysis, measurement of oxygen concentration, temperature and relative humidity.

The animals were secured in plastic animal holders (Batelle), positioned radially through the outer cylinder around the central column. Male and female rats of each group were placed in alternating order. Only the nose of the rat protruded into the interior of the column. By securing a positive pressure in the central column and a slightly negative pressure in the outer cylinder, which encloses the entire animal holder, air leaks from nose to thorax rather than from thorax to nose and dilution of test atmosphere at the nose of the animals is prevented.

The inhalation equipment was designed to expose rats to a continuous supply of fresh test atmosphere. The test atmosphere was generated by passing test material to an eductor (Fox mini, type 060, Spraybest Europe BV, Zwanenburg, the Netherlands) using a dry material feeder (Gericke GMD 60, Gericke AG, Regensburg, Switzerland). The eductor was placed at the inlet of the exposure unit and was operated with pressurized dry air controlled by a pressure reducing valve at 0.5 bar. The test material was delivered in a slip stream of humidified air. The resulting aerosol was directed downwards towards the animal noses. At the bottom of the unit the test atmosphere was exhausted. The mean flow of air was 84.8 L/min. The period between the start of the generation of the test atmosphere and the start of exposure of animals was 135 minutes.

TEST ATMOSPHERE
The concentration of the aerosol in the test atmosphere was determined once per hour by gravimetric analysis. During exposure, representative samples were obtained by passing 5 L test atmosphere samples at 5 L/min through glass fibre filters (Sartorius, 13430-44-5). Filters were weighed before sampling, loaded with aerosol particles and weighed again.

Particle size distribution measurement was carried out once in the preliminary phase and once during exposure using a 10-stage cascade impactor (Anderson, Atlanta, USA) with the largest cut-off size of 32 µm.


Temperature (21.5 +/- 0.1°C) and humidity (44 +/-1%) in air chamber were recorded eight times during exposure at regular intervals (ca. twice per hour) using an RH/T device (TESTO 610, TESTO GmbH & Co, Lenzkirch, Schwarzwald, Germany) . The oxygen concentration was checked once during exposure (Beryl, Cosma, Igny, France): 21.6%.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

by gravimetric analysis

Duration of exposure:

4 h

Concentrations:

The measured aerosol concentrations during exposure were 5.298, 4.806, 4.944, 5.022, 5.162 and 5.016 g/m3.
Mean: 5.04 +/- 0.17 g/m3 (n=6).

The nominal concentration was calculated by dividing the total amount of test material used (by calculating the yield of the feeder allowing for the adjustment of its settings) by the total volume of air passed through the exposure unit: 9.4 g/m3.

The generation efficiency was 54% (a common value).

No. of animals per sex per dose:

One group of 5 male and 5 female rats

Control animals:

no

Details on study design:

- Duration of observation period following exposure: 14 days
- Visual inspection of the rats (for behaviour, clinical signs and mortality) just before exposure, shortly after exposure and at least once daily during the observation period.
- Body weights were recorded just before exposure (day 0), on day 7 and on day 14
- Necropsy of survivors performed: yes (at the end of the 14-day observation period)
- All rats were examined for gross pathological changes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.04 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Males: 0/5
Female: 0/5

Clinical signs:

other: A slightly decreased breathing rate was seen in all animals during exposure. In a few animals (1 male and 2 female rats) slight laboured breathing was seen in the last two hours during exposure. Shortly after exposure or during the 14-day observation

Body weight:

Overall body weight gain in the animals was considered normal for rats of this strain and age.

Gross pathology:

Exposure related abnormalities were not found at necropsy.

Other findings:

During the 14-day observation period, treatment related abnormalities were not observed.

Any other information on results incl. tables

It was shown that 76% of the mass of the aerosol present at the animals' breathing zone was contained in particles with an aerodynamic diameter equal to or smaller than 5 um

The Mass Median Aerodynamic Diameter (MMAD) = 3.1 µm. The Geometric standard deviation = 1.8. (in preliminary experiment: MMAD = 3.0 µm. Geometric standard deviation = 1.6)

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute inhalation 4h-LC50 of Terracess P is > 5.04 mg/L air (rat)
TERRACESS P does not have to be classified and has no obligatory labelling requirement for inhalation toxicity.