Reaction mass of aluminium chloride, iron dichloride, magnesium chloride and manganese dichloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 March 2010 to 22 April 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The 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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (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:

no

Test material

Test material information

Constituent 1

Reference substance name:

Aluminum chloride, basic

EC Number:

215-477-2

EC Name:

Aluminum chloride, basic

Cas Number:

1327-41-9

Molecular formula:

General formula: Al(OH)x(Cl)(3-x), with x ranging from 0.1 to 2.3

IUPAC Name:

Aluminum chloride, basic

Details on test material:

- Name of test material (as cited in study report): 202029/A
- Substance type: Clear yellow liquid
- Physical state: Liquid
- Analytical purity: set at 35% for calculations in consultation with the Study Monitor
- Impurities (identity and concentrations): Not indicated
- Composition of test material, percentage of components:
Composition Per 100 gram the sample contained:
35.74 g AI(OH)1.22CI1.78
< <0.005 g insoluble substance
<0.096 g other inorganic salts
The rest is water
= 99.7 % Purity of active ingredient (water free)
8.7 % Al content
- Isomers composition: Not indicated
- Purity test date: Not indicated
- Lot/batch No.: 8700003292
- Expiration date of the lot/batch: 18 December 2010
- Stability under test conditions: Stable
- Storage condition of test material: At room temperature in the dark
- Other:
General information: Forms polymeric ions and Al(OH)3 when diluted with water, depending on pH
Density: 1.363 kg/L at 20°C
pH: 1.0 ± 0.5% (20°C)

Test animals

Species:

rat

Strain:

Wistar

Sex:

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 (approx. 11-12 weeks old) were selected.
- Weight at study initiation: 176-223 gram. Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.) containing sterilized 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).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: at least 5 days before start of treatment under laboratory conditions.
- Other details:
A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health.
Results of analysis for diet (nutrients and contaminants), sawdust, paper and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9 – 21.7ºC
- Humidity (%): 34 - 54% Temporary deviations from the minimum level of relative humidity of 40% occurred, but laboratory historical data do not indicate an effect of these deviations.
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day

IN LIFE DATES: From: 30 March 2010 to 22 April 2010

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Remarks:

Correction was made for the purity of the test substance, which was set at 35% for calculations in consultation with the Study Monitor.

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 4.19 mL/kg for 2000 mg/kg and 0.629 mL/kg for 300 mg/kg.

DOSAGE PREPARATION (if unusual):
The test substance was dosed undiluted as delivered by the sponsor. Dose levels were corrected for the purity of the test substance, which was set at 35% for calculations in consultation with the Study Monitor. Dose volumes were calculated as: Dose level (g/kg) / density (g/mL).

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Not indicated

Doses:

2000 mg/kg and 300 mg/kg. Single dosage, on Day 1.
Dose levels were corrected for the purity of the test substance, which was set at 35% for calculations in consultation with the Study Monitor.
The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.

No. of animals per sex per dose:

2000 mg/kg: 3 females
300 mg/kg: 2: 6 females (2 groups of 3 animals were treated in a stepwise fashion)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (Day 1 - Day 15)
- Frequency of observations and weighing:Clinical signs at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15 (see 'Any other information on materials and methods inc. tables). Body weights on Days 1 (pre-administration), 8 and 15 and at death.
- Necropsy of survivors performed: yes (see 'Any other information on materials and methods inc. tables)
- Other examinations performed: Mortality/viability was observed twice daily. The time of death was recorded as precisely as possible.

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

other: Dose levels in report were corrected for the purity of the test substance, which was set at 35% for calulations

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 900 - < 6 000 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

female

Dose descriptor:

other: LD50 cut-off value

Effect level:

500 mg/kg bw

Based on:

other: Dose levels in report were corrected for the purity of the test substance, which was set at 35% for calulations

Remarks on result:

other: According to the OECD 423 test guideline

Effect levels 4

Sex:

female

Dose descriptor:

other: LD50 cut-off value

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: According to the OECD 423 test guidance

Mortality:

The incidence of mortality was as follows, presented in chronological order of treatment:
Dose level Mortality Date of treatment
2000 mg/kg 3/3 30 March 2010
300 mg/kg 0/3 01 April 2010
300 mg/kg 1/3 08 April 2010

The decedents were found dead within 24 hours post-treatment.

See attached document 'Results tables'.

Clinical signs:

Clinical signs observed during the study period were as follows:
Dose level Clinical signs
2000 mg/kg Lethargy, hunched posture, piloerection and ptosis.
300 mg/kg Lethargy, hunched posture, uncoordinated movements, piloerection and/or ptosis.

The surviving animals had fully recovered from the symptoms between Days 4 and 6.

See attached document 'Results tables'.

Body weight:

The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.

See attached document 'Results tables'.

Gross pathology:

Animals that were found dead at 2000 mg/kg and 300 mg/kg showed a combination of the following findings at macroscopic post mortem examination: beginning or advanced autolysis, black-brown discolouration of the glandular mucosa of the stomach, gray-white, black-brown or reddish foci on the glandular mucosa of the stomach, hardened glandular mucosa of the stomach, dark red foci on the forestomach, distention of the stomach with gas, greenish and dark red foci on lungs, hardened lungs, dark red discolouration of the pancreas, enlargement of the spleen, reddish discolouration of the wall of the duodenum, dark red or black-brown foci on the thymus, yellowish foci on the uterus and yellowish discolouration of uterine adipose tissue in the abdominal cavity.

No macroscopic abnormalities were observed for animals at 300 mg/kg that survived until termination.

See attached document 'Results tables'.

Other findings:

Not appplicable.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on these results: LD 50 (rat, oral) > 2000 mg/kg bw based on test substance
- according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007), 202029/A should not be classified for acute toxicity by the oral route.
- according to the Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures, 202029-A should not be classified.

Executive summary:

In the study report a calculation is used to determine the dose which disregarded the water contained in the material as a solvent and use doses assuming only 35 % active in the solution. Thus, very high doses were applied.
However, basic Aluminum chloride cannot be isolated from the aqueous solution without changing the chemical composition and properties. Thus, the water in this case is not a simple solvent, that could be disregarded, but an integral consituent of the test material stabilizing the substance. The water, therefore, must not be disregarded when determining the dose. The consequence is that the dose relevant for classification & labelling is not the amount of theoretically applied active material (as done by the authors of the study) but the amount of material as it was provided; i.e. about 3- fold higher and above the limits for classification. LD 50 (rat, oral) > 2000 mg/kg bw
 

When using this approach the material does not need to be classified and labelled for acute oral toxicity.