Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study tested with the source substance CAS 39290-78-3. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
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:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Aluminum chloride hydroxide sulfate
EC Number:
254-400-7
EC Name:
Aluminum chloride hydroxide sulfate
Cas Number:
39290-78-3
Details on test material:
- Name of test material (as cited in study report): 202028/A
- Substance type: clear colourless liquid (determined at NOTOX)
- Physical state: liquid.
- Analytical purity: 17.9% , Al = 4.4%
- Lot/batch No.: 87T1-170909
- Expiration date of the lot/batch: 18 December 2010 (allocated by NOTOX, 1 year after receipt of the test substance)
- Stability under test conditions: sStable under storage conditions.
- Storage condition of test material: st room temperature in the dark
- 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 : Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) except during exposure to the test substance.
- Water: 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
- Humidity (%): 42 - 60
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12
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:
other: unchanged (no vehicle).
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.
The placement of the individual animals in the inhalation chamber is shown in figure 2. 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:
other: not required
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).

Results and discussion

Effect levels
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.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Executive summary:

Assessment of acute inhalation toxicity with 202028/A in the rat

 

The study was carried out based on the guidelines described in:

-OECD Guidelines, Section 4, Health Effects. No.403, "Acute Inhalation Toxicity", September 2009.

- Commission Regulation (EC) No 440/2008,B.2. Acute Toxicity (inhalation),L142, May 2008.

- EPA OPPTS 870.1300, Acute inhalation Toxicity. EPA 712-C-98-193, August 1998.

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

 

202028/Awas 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 5.0mm 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.