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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 August, 1995 - 24 August, 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
1995

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
(1981)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
422-150-1
EC Name:
-
Molecular formula:
Hill formula: Mg4.3 Al2(OH)12.6 (CO3)0-0.75 (ClO4)0.5-2.0 . (0-5)H2O CAS formula: Mg4.3 Al2(OH)12.6 (CO3)0-0.75 (ClO4)0.5-2.0 . (0-5)H2O
IUPAC Name:
Aluminium-magnesium-carbonate-hydroxide-perchlorate-hydrate
Test material form:
solid: particulate/powder
Details on test material:
- Appearance: white powder
- Storage condition of test material: at room temperature in the dark

Test animals

Species:
rat
Strain:
other: Crl:[WI]WU BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, Germany
- Age at study initiation: appr. 9 weeks
- Weight at study initiation: 305 - 327 g (males); 193 - 201 g (females)
- Fasting period before study: no
- Housing: Group housing of 5 animals/sex in suspended stainless steel cages
- Diet: free access to cereal-based rodent diet (SDS Special Diets Services, Witham, England) (no access to food during exposure)
- Water: free access to tap water (no access to water during exposure)
- Acclimation period: total 17 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 - 24.0
- Humidity (%): 63 - 89
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose-only inhalation chamber, a modification of the chamber manufactured by ADG Developments Ltd., Codicote, Hitchin, Herts, SG4 8UB, UK.
- Method of holding animals in test chamber: the animals were secured in plastic animal holders
- Exposure chamber volume: 150 L
- Rate of air: mean amount 104 L/min
- System of generating particulates/aerosols: The test atmosphere was generated by passing the test material using a dry material helix feeder to a jet mill. The jet mill was operated with dry pressurized air (less than 1% humidity); the test material was delivered using a slip stream of airconditioned room air and pressurized air. This stream accounted for about 55% of the total amount of air. The generated aerosol was passed to the inlet of the exposure unit and was directed downward through the mixing chambers towards the animal noses. At the bottom of the unit the test atmosphere was exhausted.
- Method of particle size determination: Twice during exposure using a 10-stage Anderson cascade impactor with the largest cut-off size of 32 µm. Due to a technical failure these measurements could not be used to determine the particle size distribution. The particle size distribution measurement, however, had also been carried out the day before exposure during a test run at exactly the same settings as during exposure.
- Treatment of exhaust air: no data
- Temperature, humidity in air chamber: 20. 5 - 21.0°C; 41 - 58%

TEST ATMOSPHERE
- Brief description of analytical method used: The actual concentration in the test atmosphere was determined twice each hour by gravimetric analysis. The nominal concentration was determined by dividing the total amount of test material used by the total volume of air passed through the exposure unit.
- Samples taken from breathing zone: Representative samples were obtained by passing test atmosphere samples at ca. 5 L/min through fiber glass filters. Before sampling the filters were weighed; immediately after sampling the filters were weighed again. The actual concentration was calculated by dividing the amount of test material present on each filter by the volume of the test atmosphere sample taken.

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.9 µm / 2.2 µm

CLASS METHOD
- Rationale for the selection of the starting concentration: Based on the cut off concentration values specified in the UN and EC classification guidelines.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5 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 observations and weighing:
Behaviour, clinical signs and mortality: The rats were visually inspected just before exposure, for reactions to treatment during the exposure, shortly after exposure, and at least once daily during the observation period.
Body weights: Body weights were recorded just prior to exposure (day 0), and on days 7 and 14.
- Necropsy of survivors performed: At the end of the 14 day observation period, all rats were killed by exsanguination from the abdominal aorta under ether anaesthesia. All rats were necropsied and examined for gross pathological changes.
Statistics:
No statistical analysis was performed (the method used was not intended to calculate a LC50 value).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No animals died.
Clinical signs:
other: Slight visually decreased breathing rate was observed in all rats ca. 1.5, 2.5 and 3.5 hours after the start of the exposure. Two males and one female felt cold upon touching shortly after exposure. Dirty fur of the head was seen in 2 females until day 7
Body weight:
Slightly reduced mean body weight gain was generally seen in all rats 7 days after exposure. Normal body weight gain was observed in males at the end of the observation period, whereas body weight gain remained low in 3 females.
Gross pathology:
No abnormalities were observed at necropsy, except for one female that showed sparsely haired abdomen.
Other findings:
None.

Any other information on results incl. tables

The mean actual concentration of the substance during the exposure based on gravimetric analyses was 5.16 ± 0.48 mg/L.

The nominal concentration was calculated to be 14.7 mg/L indicating a generation efficiency of ca. 35%.

The particle size distribution: it was shown that 91.2% of the particles present at the animals' breathing zone were of the respitable size range since they were smaller than or equal to 5.0 µm.

MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.9 µm / 2.2 µm

Applicant's summary and conclusion

Interpretation of results:
other: Not classified.
Remarks:
According to Regulation (EC) No. 1272/2008 and its amendments.
Conclusions:
In an acute inhalation toxicity study with male and female rats, performed according to OECD 403 test guideline and GLP principles, an LC50 >5 mg/L was determined for ALCAMIZER 5.




Executive summary:

Alcamizer 5 was tested in an acute inhalation toxicity study with nose-only exposure with male and female rats, performed according to OECD 403 test guideline and GLP principles.

No mortality occurred. Slight visually decreased breathing rate was observed in all rats ca. 1.5, 2.5 and 3.5 hours after the start of the exposure. Two males and one female felt cold upon touching shortly after exposure. Dirty fur of the head was seen in 2 females until day 7 of the 14 day observation period. One female additionally showed alopecic areas on the fur on days 7-14. Slightly reduced mean body weight gain was generally seen in all rats 7 days after exposure. Normal body weight gain was observed in males at the end of the observation period, whereas body weight gain remained low in 3 females. No abnormalities were observed at necropsy, except for one female that showed sparsely haired abdomen.

Based on the results, an LC50 >5 mg/L was determined. Alcamizer 5 does not have to be classified and has no obligatory labelling requirement for acute inhalation toxicity according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).