Registration Dossier

Administrative data

Description of key information

- Acute toxicity: oral:
The acute oral median lethal dose to rats of Aluminum sulphate, hydrate was found to be greater than 2000 mg/kg bodyweight and less than 5000 mg/kg bw (comparable to OECD 401, Kr: 2).
- Acute toxicity: dermal:
The Single Dose Acute Dermal LD50 of Aluminum Sulfate, Hydrate applied to the skin for 24 hours, is greater than 5000 mg/kg bw (comparable to OECD 402, Kr: 2) .
- Acute toxicity: inhalation:
No data available on the registered substance. However, two studies performed on analogous (CAS N°: 39290-78-3 and Catapal Alumina Fines) were available. In these studies (OECD 403, Kr. 2, GLP), the LC50, 4h value (droplet or particle aerosol) in rats was considered to exceed 5 mg/L.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Only raw data were reported, details on test materials are missing. Guideline 401 is followed with deviations.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
: not always a 14 day observation period.
Principles of method if other than guideline:
Not applicable.
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
No data
Route of administration:
oral: unspecified
Vehicle:
other: water or Tween 80 with water
Details on oral exposure:
No data
Doses:
- 2000 mg/kg
- 5000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (not always a 14 day observation period.)
- Frequency of observations and weighing: observations: daily
- Necropsy of survivors performed: yes
Statistics:
No data
Preliminary study:
Not relevant
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 - < 5 000 mg/kg bw
Sex:
male
Dose descriptor:
LD50
Effect level:
< 5 000 mg/kg bw
Mortality:
- No animals died following treatment or during the observation period at the 2000 mg/kg dosage.
- All animals died during the observation period at the 5000 mg/kg dosage. Deaths occurred on the first or second day.
Clinical signs:
- All rats generally exhibited normal appearance and behaviour following treatment and during the observation period at the 2000 mg/kg dosage.
- Clinical observation data at the 5000 mg/kg dosage: The most frequently observed changes included depression, ruffled fur and nearly closed eyes or glossy eyes.
Body weight:
No data
Gross pathology:
- Animals in the 2000 mg/kg group with water as a vehicle showed no gross abnormalities.
- The observed changes of the gross necropsies performed on animals which died during the observation period included very red lung edges and swollen stomach.
Other findings:
See table below (Table 7.2.1/1)

Table 7.2.1/1: Results on deaths, clinical and necropsy observations:

Date

Sex

Dose

(mg/kg)

Vehicle

# deaths

Total #

animals

Clinical observations

Necropsy observations

8July1976

M

5000

Tween 80 + H2O

5

5

Day 1:

- Restless

- Ruffled fur

- Lying in one place

- Occasionally readjust positions

- React to touch + sound

Day 2:

- Remaining rat sits in one place, wobbling slightly

- Head rests on floor

- Eyes sunken + glossy

- Fur ruffled

Day 2:

- Lung edges very red

- Stomach swollen; content reddish

- Yellow liquid filled mouth during necropsy

 

 

 

 

 

 

 

 

18June1976

F

2000

Tween 80 + H2O

0

5

Appear normal

 

13July1976

F

5000

Tween 80 + H2O

5

5

Day 1:

- Mild to severe depression

- Slower reacting to sound + touch

- Ruffled fur

- Walking uncoordinated

- Eyes partially closed

- Huddled in a pile

- Mild lacrimation

- 1 animal died

Day 2:

- Other animals died

 

03August1976

F

2000

H2O

0

5

Appear normal

No gross abnormalities

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions of this study, the acute oral median lethal dose to rats of Aluminum sulphate, hydrate was found to be greater than 2000 mg/kg body weight and less than 5000 mg/kg bw. Based on these results, the registered substance is not classified according to EU criteria.
Executive summary:

In an acute oral toxicity study performed with some equivalence to OECD Guideline 401 but not in compliance with GLP, groups (5/sex/dose) of Sprague Dawley rats were given Aluminum sulphate, hydrate at 2000 mg/kg in water or in Tween 80/water to females and 5000 mg/kg in Tween 80/water to males and females.Animals were then observed for mortality, clinical signs for 14 days in most cases and were all sacrificed for macroscopic examination.

No mortality occurred in all ten females dosed at the 2000 mg/kg level. No clinical changes were observed generally at this dose level. All ten animals at 5000 mg/kg bw died with deaths occurring on the first or second day. Clinical signs of toxicity included depression and ruffled fur. Necropsy findings showed very red lung edges and/or swollen stomach.

 

The acute oral LD50 for Aluminum sulphate, hydrate was found to be greater than 2000 mg/kg bodyweight and less than 5000 mg/kg bw for females. For males the LD50 is less than 5000 mg/kg. Based on these results, the registered substance was not classified according to the Regulation (EC) N° 1272-2008 (CLP) and the Directive 67/548/EEC criteria.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Study performed similarly to OECD guideline 401 with Klimisch rate of 2.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
5 000 mg/m³
Quality of whole database:
Studies performed similarly to OECD guideline 403 with Klimisch rate of 2.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Only raw data were reported, details on test materials are missing. Guideline 402 is followed with deviations.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
: only 2 males and 2 females tested
Principles of method if other than guideline:
Not applicable.
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
No data
Type of coverage:
not specified
Vehicle:
not specified
Details on dermal exposure:
No data
Duration of exposure:
24 hours
Doses:
5000 mg/kg
No. of animals per sex per dose:
2 males and 2 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations: daily; weighing: at start and end of the test
- Necropsy of survivors performed: yes
Statistics:
No data
Preliminary study:
Not applicable.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred following treatment and during the observation period at the 5000 mg/kg dosage level.
Clinical signs:
Clinical observation data at the 5000 mg/kg dosage:
- Males: mild/moderate erythema. Both appear normal 2 days after treatment.
- Females: moderate and severe erythema, small areas of haemorrhaging in places where large chunks of compound were pressed into the skin. Both appear normal 2 days after treatment.
Body weight:
No data
Gross pathology:
Animals autopsied in the 5000 mg/kg group showed no gross abnormalities, with the exception of 1 male animal which had pale lungs.
Other findings:
See Table below (Table 7.2.3/1)

Table 7.2.3/1: results on deaths, clinical and necropsy observations:

Date

Sex

Dose

(mg/kg)

# deaths

Total #

animals

Clinical observations

Necropsy observations

15July1976

M

5000

0

2

After unwrapping:

- Mild/moderate erythema

Day 2:

- Appear normal

One animal with pale lungs, other animal showed no gross abnormalities

 

 

 

 

 

 

 

15July1976

F

5000

0

2

Day 1:

- Moderate and severe erythema

- Small areas of haemorrhaging in places where large chunks of compound were pressed into the skin

Day 2:

- Appear normal

No gross abnormalities

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions of this study, the Single Dose Acute Dermal LD50 of Aluminum Sulfate, Hydrate applied to the skin for 24 hours, is greater than 5000 mg/kg bw. Therfore the test material was not classified according to EU criteria.
Executive summary:

In an acute dermal toxicity study performed with some equivalence to OECD Guideline 402 but not in compliance with GLP, groups (2/sex/dose) of New Zealand White rabbits were tested with a single dermal application of Aluminum Sulfate, Hydrate at 5000 mg/kg bw for 24 hours. Animals were then observed for mortality, clinical signs for 14 days and were all sacrificed for macroscopic examination.

No mortality occurred. All rabbits exhibited normal appearance and behaviour on day 2. However, some skin irritation such as erythema and haemorrhaging were observed.The gross necropsy showed no significant gross changes, with the exception of 1 male animal which had pale lungs.

The Single Dose Acute Dermal LD50 of Aluminum Sulfate, Hydrate applied to the skin for 24 hours, is greater than 5000 mg/kg bw. Therfore the registered substance was not classified according to the Annex VI of the Regulation EC No.1272/2008 (CLP) and of the Directive 67/548/EEC criteria.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw
Quality of whole database:
Study performed similarly to OECD guideline 402 with Klimisch rate of 2.

Additional information

Acute toxicity : oral

A key study was identified (Scholler, 1975). This acute oral toxicity study was performed with some equivalence to OECD Guideline 401 but in pre-GLP. Groups (5/sex/dose) of Sprague Dawley rats were given Aluminum sulphate, hydrate at 2000 mg/kg in water or in Tween 80/water to females and 5000 mg/kg in Tween 80/water to males and females.

 

No mortality and nor clinical signs were observed at 2000 mg/kg bw. All ten animals at 5000 mg/kg bw died with deaths occurring on the first or second day. Clinical signs of toxicity included depression and ruffled fur. Necropsy findings showed very red lung edges and/or swollen stomach.

 

Under the test conditions of this study, the acute oral LD50 for Aluminum sulphate, hydrate was found to be greater than 2000 mg/kg bw and less than 5000 mg/kg bw.

Acute toxicity : dermal :

One study was available and selected as key study (Scholler, 1976). This acute dermal toxicity study was performed with some equivalence to OECD Guideline 402 but in pre-GLP. Groups (2/sex/dose) of New Zealand White rabbits were tested with a single dermal application of Aluminum Sulfate, Hydrate at 5000 mg/kg bw for 24 hours.

No mortality occurred. All rabbits exhibited normal appearance and behaviour on day 2. However, some skin irritation such as erythema and haemorrhaging were observed.The gross necropsy showed no significant gross changes, with the exception of 1 male animal which had pale lungs.

Under the test conditions of this study, the Single Dose Acute Dermal LD50 of Aluminum sulphate hydrate applied to the skin for 24 hours, is greater than 5000 mg/kg bw.

Acute toxicity : inhalation

No data available on the registered substance. However, two acute toxicity studies performed on analogues (CAS N°: 39290 -78 -3 and Catapal Alumina Fines) were available and reliable for the assessment of acute inhalation toxicity. These studies were performed according to OECD guideline 403 with Klimisch rate of 2. No clinical or macroscopic systemic effect was observed.

In both studies, the inhalation LC50, 4h value (droplet or particle aerosol) in rats was considered to exceed 5 mg/L. Based on Weight of evidence approach, the registered substance was considered as not harmful by inhalation route.


Justification for selection of acute toxicity – oral endpoint
Two acute toxicity studies performed similarly to OECD 401 (Kr : 2, Pre-GLP) were available. The study identified as the key study was the one with the lowest LD50 range.

Justification for selection of acute toxicity – inhalation endpoint
No data available on the registered substance. However, two acute toxicity studies performed on analogous (Kr : 2, OECD 403, GLP) were available.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 including ATP3.

Self classification:

Acute toxicity via Oral route:

Based on the available data, the substance is:

- not classified according to the Regulation (EC) No. 1272/2008 as the LD50 is greater than 2000 mg/kg bw.

- not classified according to the Directive 67/548/EEC as the LD50 is greater than 2000 mg/kg bw.

Acute toxicity via Dermal route:

Based on the available data, the substance is:

- not classified according to the Regulation (EC) No. 1272/2008 as the LD50 is greater than 5000 mg/kg bw

- not classified according to the Directive 67/548/EEC as the LD50 is greater than 5000 mg/kg bw.

Acute toxicity via Inhalation route:

No data available on the registered substance. However, based on the results of the studies performed on analogous, the registered substance is not classified according to the Regulation (EC) No. 1272/2008 and the Directive 67/548/EEC criteria.