Aluminum chloride hydroxide sulfate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 March 2010 - 05 April 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

This study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: - JMAFF, 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

solid - liquid: aqueous solution

Details on test material:

- Physical state: Clear colourless liquid (determined at NOTOX)
- Expiration date of the lot/batch: 18 December 2010 (allocated by NOTOX, 1 year after receipt of the test substance)
- Storage condition of test material: At room temperature in the dark
- Stability under storage conditions: Stable
- Other:
Density: 1.189 kg/L at 21°C
pH: 3.0 ± 0.5% (20°C)

Test animals

Species:

rat

Strain:

other: Crl:WI(Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals were selected (approximately 10 weeks old).
- Weight at study initiation: body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: No.
- Housing:
Before exposure
Group housing of five animals per sex per cage in labelled Macrolon cages (type IV; height 18 cm) containing sterilised sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
After exposure
Group housing as described above, except that a paper sheet was introduced into the cage covering the bedding and cage enrichment to prevent suffocation in case of bad health condition. At the end of the Day of exposure the paper sheet was removed.
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) except during exposure to the test substance.
- Water (e.g. ad libitum): Free access to tap water except during exposure to the test substance.
- Acclimation period: At least 5 days before start of treatment under laboratory conditions.
- Health inspection: A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health

Animals 4 and 5 were replaced by spare animals, 30 minutes after start of exposure, and exposed immediately after restraining. The animals were not acclimatised for at least 15 minutes. The animals were replaced since the original animals were found dead during exposure, possibly caused by stress due to restraining. Since the exposure was ongoing, it was not possible to acclimatise the animals to restraining. It was considered that this event did not affect the exposure results for these animals.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8 – 21.7°C
- Humidity (%): 42 - 60%
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 22 March 2010 To: 05 April 2010

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Remarks:

unchanged

Mass median aerodynamic diameter (MMAD):

ca. 4 - ca. 5 mm

Geometric standard deviation (GSD):

ca. 1.7

Remark on MMAD/GSD:

The droplet size distribution was representatively characterized twice during the exposure period. The samples were drawn (2 L/min) from the test atmosphere through a tube mounted in one of the free animal ports of the middle section of the exposure chamber (appendix 1, figures 1 and 2). The samples were collected with an 8 stage Marple personal cascade impactor containing fiber glass filters (SKC 225-713, Fiber glass, SKC Omega Specialty Division, Chelmsford, MA, USA) and a fiber glass back-up filter (-290-F1, Westech, Upper Stondon, Bedfordshire, England). Amounts of test substance collected were measured gravimetrically. Subsequently the Mass Median Aerodynamic Diameter (MMAD) and the Geometric Standard Deviation (GSD) were determined.
 
The Mass Median Aerodynamic Diameter (MMAD) and geometric standard deviation (gsd) were determined twice. The MMAD was 4.0 and 5.0mm and the gsd was 1.7 at both occasions.

Details on inhalation exposure:

The design of the exposure chamber is based on the flow past nose-only inhalation chamber (Am. Ind. Hyg Assoc. J. 44(12): 923-928, 1983). The chamber consisted of three animal sections with eight animal ports each. Each animal port had its own atmosphere inlet and exhaust outlet. The animals were placed in restraining tubes and connected to the animal ports. The number of animal sections and number of open inlets were adapted to the air flow in such a way that at each animal port the theoretical air flow was at least 1 L/min, which ensures an adequate oxygen supply to the animals. The main inlet of the test atmosphere was located at the top section and the main outlet was located at the bottom section. The direction of the flow of the test atmosphere guaranteed a freshly generated atmosphere for each individual animal.
All components of the exposure chamber in contact with the test material were made of stainless steel, glass, rubber or plastic. To avoid exposure of the personnel and contamination of the laboratory the exposure chamber was placed in a fume hood, which maintained at a slight negative pressure.

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

4 h

Concentrations:

1.6 mg/L, corresponding to 6.1 mg/L of the neat test substance (correction factor 3.7 for the evaporable water content).

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

202028/A was administered as an aerosol by inhalation for 4 hours to one group of five male and five female Wistar rats. Animals were subjected to daily observations and determination of body weights on Days 1, 2, 4, 8 and 15. Macroscopic examination was performed after terminal sacrifice (day 15).

Statistics:

No data.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

5 mg/L air

Exp. duration:

4 h

Mortality:

No mortality occurred.

Clinical signs:

other: Clinical signs observed among most animals after exposure included lethargy, hunched posture and/or piloerection on Days 1 and/or 2. No clinical signs were observed during exposure

Body weight:

Mean body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Other findings:

None.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the inhalatory LC50, 4h value of the substance 202028/A (aerosol) in rats was considered to be higher than 5 mg/L. Therefore, no classification is required according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

Executive summary:

An acute toxicity study by inhalation was performed according to the OECD guideline No. 403 and in compliance with GLP. 202028/A was administered as an aerosol by inhalation for 4 hours to one group of five male and five female Wistar rats. Animals were subjected to daily observations and determination of body weights on Days 1, 2, 4, 8 and 15. Macroscopic examination was performed after terminal sacrifice (day 15).

The mean actual dry test substance concentration was 1.6 ± 0.5 mg/L, corresponding to 6.1 ± 1.8 mg/L of the neat test substance (correction factor 3.7 for the evaporable water content). The mean nominal concentration was 9.4 mg/L resulting in a generation efficiency (ratio of mean actual concentration and nominal concentration of neat test substance) of 65%.

The concentration measurements conducted equally distributed over time showed that the substance was sufficiently stable.

The Mass Median Aerodynamic Diameter (MMAD) and geometric standard deviation (gsd) were determined twice. The MMAD was 4.0 and 5.0 μm and the gsd was 1.7 at both occasions.

No mortality occurred.

Clinical signs observed among most animals after exposure included lethargy, hunched posture and/or piloerection on Days 1 and/or 2. No clinical signs were observed during exposure.

The body weight gain shown by the animals over the study period was considered to be normal.

No abnormalities were found at macroscopic post mortem examination of the animals.

Agglomeration of aerosol particles at this high concentration of 5 mg/L may have resulted in one MMAD value to exceed the recommended range of 1 - 4 μm (values obtained were 4.0 and 5.0 μm). Since the values were close to or at the top of the range, it was considered that sufficient test substance deposition in the lower respiratory tract occurred during the exposure in order to give a reliable outcome.

LC50(4h, aerosol) > 5 mg/L air

Under the test conditions of this study, the inhalatory LC50, 4h value of 202028/A (aerosol) in rats was considered to exceed 5 mg/L. Based on these results, no classification is required according to Regulation (EC) No 1272/2008 (CLP) and to the GHS.