Aluminium triformate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 January 2010 to .............

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Aluminium triformate

EC Number:

230-898-1

EC Name:

Aluminium triformate

Cas Number:

7360-53-4

Molecular formula:

CH2O2.1/3Al

IUPAC Name:

aluminium triformate

Details on test material:

Size distribution: L10=5.9 µm, L50=13.4 µm, L90=46 µm.

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 Deutschland GmbH, Sulzfeld, Germany
- Age at study initiation: 8 to 9 weeks
- Weight at study initiation: 310 to 340 g (male) and 230 to 260 g (female)
- Fasting period before study: no
- Housing: Single caging in Makrolon cages type III (39 cm x 23 cm x 18 cm). Wire mesh lids.
- Diet (e.g. ad libitum): Ssniff R/M-H maintenance diet for rats and mice (item V1534-300), ad libitum.
- Water (e.g. ad libitum): Tap water, acidified with HCl to a pH of >3, from an automatic watering system, ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.4 °C
- Humidity (%): 53.4 %
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12+12

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 'nose-only' inhalation apparatus (TSE Systems GmbH, Bad Homburg, Germany; article no. 504101
- Exposure chamber volume: 19 L
- Method of holding animals in test chamber: Inhalation tubes
- Source and rate of air: Oil free, dried air from a central pressure pump, 1070 L/h
- System of generating particulates/aerosols: A dust generator acc. to Bundschuh (for the low and mid concentration) or acc. to Budiman (for the high concentration) , from TSE Systems GmbH, Bad Homburg, Germany
- Method of particle size determination: Cascade impactor (Berner-Impaktor Type LPI4/0,06/2 from Hauke KG, Gmunden, Austria with nine steps with cut-off- diameters from 0.06 µm to 16 µm.
- Temperature, humidity in air chamber: 20.6 to 21.2 °C, 12 to 38 % relative humidity


TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric analysis
- Samples taken from breathing zone: yes


TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 6.3 µm / 2.0 (low and mid concentration), 9.9 µm / 3.0 (high concentration)

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

4 h

Concentrations:

0.37, 1.29 and 2.51 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: during the acclimatisation period, before administration, 1, 3, 7 and 14 days p.a.
- Frequency of observations: 6 times on the day of exposure, once a day after.
- Necropsy of survivors performed: yes
- Histopathology of the lungs of the mid and high dosed group

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.51 mg/L air

Exp. duration:

4 h

Remarks on result:

other: 95 % CL is not calculatable.

Mortality:

All animals survived.

Clinical signs:

other: All animals of all groups were normal during the 14 days of the observation period.

Body weight:

The animals lost weight the first day after the exposure. This is caused by the restraining in the inhalation tube and not necessarily test substance related. The next days, most animals gained weight. There is no statistically significant linear correlation between the dust concentration and the body weight gain at any time after the exposure. There is however a clearly reduced body weight development in the high concentration group compared with the other two groups.

Gross pathology:

Nothing abnormal was seen in any of the animals.

Other findings:

- Histopathology: Perivascular oedema are considered to be fixation artefacts. Both alveolar and interstitial haemorrhages may be related to the test substance. They occurred randomly in both tested groups with a low degree of severity.

Any other information on results incl. tables

See Attachment.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The inhalation exposure of rats to "Aluminium triformate" at the maximal technically feasible concentration of 2.51 mg/L did not produce signs of toxicity. All animals survived and no well-defined adverse effects were observed during the 14-day observation period. Only the body weight gain in the high concentration group was reduced and histologically alveolar and interstitial haemorrhages were seen with a low degree of severity.
The differences to the results in the preliminary experiments, in which severe toxic signs were noted, may be explained as following:
• The animals in the preliminary experiments were smaller than in the main study, resulting in a higher breath volume per kg body weight.
• The dust concentration in the main experiment was slightly lower than in the preliminary experiment.
Therefore it is likely that the high concentration in this study is close to a concentration which would be toxic, but that a toxic dust concentration cannot be produced reproducible due to the properties of the test substance.
The LC50, per inhalation, four hours exposure, of "Aluminium triformate" for male and female rats is therefore greater than 2.51 mg per litre air which is the highest technically feasible dust concentration.

Executive summary:

The inhalation exposure of rats to"Aluminium triformate" at the maximal technically feasible concentration of 2.51 mg/L did not produce signs of toxicity. All animals survived and no well-defined adverse effects were observed during the 14-day observation period. Only the body weight gain in the high concentration group was reduced and histologically alveolar and interstitial haemorrhages were seen with a low degree of severity.

The differences to the results in the preliminary experiments, in which severe toxic signs were noted, may be explained as following:

·        The animals in the preliminary experiments were smaller than in the main study, resulting in a higher breath volume per kg body weight.

·        The dust concentration in the main experiment was slightly lower than in the preliminary experiment.

Therefore it is likely that the high concentration in this study is close to a concentration which would be toxic, but that a toxic dust concentration cannot be produced reproducibly due to the properties of the test substance.

The LC50, per inhalation, four hours exposure, of"Aluminium triformate" for male and female rats is therefore greater than 2.51 mg per litre air which is the highest technically feasible dust concentration.