Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2009-04-20 - 2009-11-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
The target concentration for a limit test of 5 mg/L could not be obtained. Therefore the maximal technical feasible concentration was 3.5 mg/L.
GLP compliance:
yes (incl. certificate)
Test type:
fixed concentration procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Hygiene: Optimal hygienic conditions.
Room number: EH1-23.
Room temperature: Median = 20.8°C, Range = 20.3 to 21.4 °C
Relative humidity: Median = 39.9 %, Range = 36.6 to 49.8 %.
Air exchange: About 12 / h.
Light: Artificial light from 6 a.m. to 6 p.m.
Cages: Single caging in Makrolon cages type III (39 cm x 23 cm x 18 cm). Wire mesh lids.
Bedding material: Aspen wood chips, Fa. ABEDD Dominik Mayr KEG, A-8580 Köflach, autoclaved. Random samples of the bedding material are analysed for contaminants by the supplier. Changes 1 / week.
Environmental enrichment: Nibbling wood bricks (10 cm x 2 cm x 2 cm) and nesting material, both from the same material and source as the bedding material, were offered to the animals once a week.
Water: Tap water from an automatic watering system, ad libitum.
Feed: Ssniff R/M-H maintenance diet for rats and mice (item V1534-300) ad libitum, supplied by Ssniff Spezialdiäten GmbH, 59494 Soest, Germany. Analysis of the feed for ingredients and contaminants is performed randomly by Ssniff.
Identification: Labelling with felt-tipped pen on the tail and on the cage.
Acclimatisation: At least 5 days.

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
The test substance was administered in a 'nose-only' inhalation apparatus (TSE Systems GmbH, Bad Homburg, Germany; article no. 504101). It consisted of a two chamber system. The apparatus was 30 cm in diameter and 27 cm in height, resulting in a total volume of 19 litres. In the twenty openings of the outer chamber, the inhalation tubes with the animals were situated. As only ten animals were administered, only the openings in the upper row were used. Neither feed nor water was offered to the animals during the exposure.
The air (700 L/h) was inserted via the central opening in the bottom, it escaped via the upper central opening and via the animal tubes.
The inhalation chamber was situated in a fume cupboard.
A dust generator acc. to Bundschuh, from TSE Systems GmbH, Bad Homburg, Germany, was used.
Before starting the test, the following experiments were made to obtain more information about the test substance:

• It was tried to produce a dust with an actual concentration of 5 mg test substance per litre.
• Two rats were exposed during the dust generation to obtain first results about the toxicity of the test substance.

The original test substance is a powder which contains some loose lumps which may impede the dust generator. Therefore it was sieved through a 0.15 mm sieve. With the help of a brush the lumps were broken and practically the whole test substance passes the sieve. The test substance powder was sticky. The metering in the dust generator, which was done by trickling through a slit, was somewhat non uniform.
Dust concentrations of 2 to 3 mg/L were obtained. Two rats were exposed to that dust for one hour. The animals showed no signs of toxicity
Therefore it was decided to sieve the test substance and to perform a limit test with the highest technically feasible dust concentration.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
3.5 mg/L
No. of animals per sex per dose:
5 female and 5 male rats
Control animals:
no

Results and discussion

Preliminary study:
Dust concentrations of 2 to 3 mg/L were obtained. Two rats were exposed to that dust for one hour. The animals showed no signs of toxicity
Therefore it was decided to sieve the test substance and to perform a limit test with the highest technically feasible dust concentration.
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 3.5 mg/L air
Exp. duration:
4 h
Mortality:
All animals survived till the end of the study.
Clinical signs:
other: All animals were normal during the 14 days of the observation period.
Body weight:
The mean body weights at the day of the exposure were 362 g for males and 235 g for females. All animals lost weight the first days after the exposure but gained weight again within the 14 days of the observation period.
As the weighing one and three days after the exposure is new in the guideline, no historic data exist in our test facility. Therefore 2 males and 2 females of the same group of animals were sham exposed (sitting in the inhalation tubes for 4 hours in normal air) one week later and the weights were recorded for comparison. Also these animals lost weight the first time after the sham exposure, but to a smaller extent. Because of the small number of sham exposed animals a good statistic evaluation is not possible.
It can therefore be assumed that the exposure caused some reduced wellness to the animals, although no signs were seen during the animal observations.
Gross pathology:
Nothing abnormal was seen in any of the animals. Some grey material, obviously rests of the test substance, was seen in the lungs of all animals. The blood content in the alveolar lumina is a response to a damage of the tissue. This effect was only minimal expressed in 5 of 10 animals. The proliferation of pneumocyte type II cells, seen in 2 animals, may be a response to changed conditions in the lung.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Justification for read-across:
Spinel type minerals all have a spinel crystal structure, no water solubility and high melting points.
Their behaviour in water and biological systems is dominated by their insolubility and missing bioavailability. They constitute in general practically inert materials also with regard to their content of metal ions. Thus, they to not contribute to any ecological hazards.

They are also not bioavailable in vivo, which was confirmed by solubility tests in surfactant and stomach/small intestine fluids.
The Spinel type minerals are not skin irritating and not eye irritating in the conducted in vitro tests.

Physico-chemical properties of Spinel and Pleonaste:

Spinel Pleonaste
density (g/cm3): 3.55 3.82
melting-point (°C): 2135 > 1650
water-solubility: insoluble insoluble
bioavailability in the digestive tract: not bioavailable not bioavailable
bioavailability in the lung: not bioavailable not bioavailable
Conclusions:
The inhalation exposure of rats to "SPINEL" at the maximal technically feasible concentration of 3.5 mg/L did not produce signs of toxicity. All animals survived and no adverse effects were observed during the 14-day observation period. Histologically rests of the test substance and borderline signs of tissue damage were seen.
The LC50, per inhalation, four hours exposure, of "SPINEL" for male and female rats is therefore greater than 3.5 mg per litre air which is the highest technically feasible dust concentration.
Applying read-across it can be assumed that the LC50 for acute inhalation of Pleonaste is greater than 3.5 mg/L.
Executive summary:

Justification for read-across:

Spinel type minerals all have a spinel crystal structure, no water solubility and high melting points. Their behaviour in water and biological systems is dominated by their insolubility and missing bioavailability. They constitute in general practically inert materials also with regard to their content of metal ions. Thus, they to not contribute to any ecological hazards. They are also not bioavailable in vivo, which was confirmed by solubility tests in surfactant and stomach/small intestine fluids. The Spinel type minerals are not skin irritating and not eye irritating in the conducted in vitro tests.

Physico-chemical properties of Spinel and Pleonaste:

  Spinel  Pleonaste 
density (g/cm3)  3.55  3.82
melting-point (degree C) 2,135  > 1,650 
water-solubility  insoluble   insoluble
bioavailability in the digestive tract not bioavailable  not bioavailable 
bioavailability in the lung   not bioavailable

 not bioavailable

 crystal structure  spinel lattice  spinel lattice

Conclusions:

The inhalation exposure of rats to"SPINEL"at the maximal technically feasible concentration of 3.5 mg/L did not produce signs of toxicity. All animals survived and no adverse effects were observed during the 14-day observation period. Histologically rests of the test substance and borderline signs of tissue damage were seen.

The LC50, per inhalation, four hours exposure, of "SPINEL" for male and female rats is therefore greater than 3.5 mg per litre air which is the highest technically feasible dust concentration.

Applying read-across it can be assumed that the LC50 for acute inhalation of Pleonaste is greater than 3.5 mg/L.