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:
comparable to guideline study with acceptable restrictions
Remarks:
Only raw data were reported, details on test materials are missing. Guideline 401 is followed with deviations.
Reason / purpose:
reference to same 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:
Category 5 based on GHS criteria
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 the Regulation (EC) N° 1272-2008 (CLP) and classified in classified in category 5 according to the GHS.
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 classified in category 5 according to the GHS.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
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

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
26. Feb. 1990 - 29. Feb. 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
No justification given for concentration tested, study was terminated shortly after exposure (3 days), observation period should have lasted for 14 days.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
short period of post exposure observations and no justification for test concentration given
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Remarks:
naive albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc., Houston, Texas
- Age at study initiation: young adult
- Weight at study initiation: males (272 - 337 g), females (204 - 264 g)
- Fasting period before study:
- Housing: 1 - 3 per cage (males separated from females) in suspended, wire bottom, stainless steel cages, during exposure animals were kept one per cage
- Diet: Purina Formulab Chow #5008, ad libitum except during exposure period
- Water: tap water, ad libitum from automatic water system, except during exposure period
- Acclimation period: at least one week

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel dynamic flow inhalation chamber
- Exposure chamber volume: 500 L
- Method of holding animals in test chamber: in cages, with one animal per cage
- Source and rate of air: filtered air
- Method of conditioning air: concentrated aerosol was diluted with filtered air and drawn into exposure chamber
- System of generating particulates/aerosols: The aerosol was generated using a Gem T Trost Air Mill coupled with a motor driven revolving disc delivery system and then combined with filtered air and drawn into the exposure chamber. Air flow in the chamber was maintained through the use of a calibrated critical orifice.
- Method of particle size determination: was done using an Andersen cascade impactor
- Temperature, humidity in air chamber: control group - temp.: 21 - 22°C; humidity: 77 - 86 %, treatment group - temp.: 19.5 - 20.5°C; humidity: 67-76 %

TEST ATMOSPHERE
- Brief description of analytical method used: The concentration of test material in the exposure atmosphere was determined gravimetrically twice per hour and nominally at the end of the exposure period. The gravimetric concentration was determined by passing a known volume of exposure air through a pre-weighed filter and the dividing the amount of test material deposited on the filter by the volume of air which passed through the filter. The nominal concentration was determined by dividing the loss in the weight of the test material after the exposure by the total volume of air which passed through the chamber.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: see table1 under any other informations on materials and methods including tables
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): at 2,75 hours - 5.423 µm/3.038 µm; at 4 hours - 4.645 µm/3.162 µm

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: not given
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetricalls
Duration of exposure:
4 h
Concentrations:
5.09 mg/L
No. of animals per sex per dose:
10 males and 10 females
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 72 hours post exposure
- Frequency of observations and weighing: weighing - before and during the post-exposure period, general observations, toxic signs and mortality were recorded at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 24 hours and 2 and 3 days post exposure
- Necropsy of survivors performed: yes (at 24 and 72 hours after exposure)
- Other examinations performed: clinical signs, body weight, histopathology of nasal turbinates, lung and trachea
Statistics:
Particle size distribution was calculated by using Probit analysis, Finney, D.J.: Probit analysis, 3rd Edition, Chapter 3 and 4, 1971, Cambridge University Press; Statistical analysis were conducted using 48 K APPLE II PLUS computers
Preliminary study:
Not available
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.09 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No deaths were observed in Al-exposed male and female rats at any observation time.
Clinical signs:
other: Control animals did not show any clinical signs during the study. Treated animals showed piloerection, decreased activity and ptosis (see summary table3). Piloerection and decreased activity were slightly more prominent in females than in males. All signs
Body weight:
No changes in body weight were observed following inhalation exposure for 4 hours to high concentration of Catapal Alumina Fines at 24 and 72 hours post exposure.
Gross pathology:
No observable abnormalities were recorded during gross necropsy examination after 24 and 72 hours of post exposure in both males and females.
Other findings:
- Organ weights: not reported
- Histopathology: No histopathological abnormalities were observed in nasal turbinate, lungs and trachea during microscopic histological examination in any of the treated animals.

Table7.2.2/3: Clinical signs observed

Reactionand severity  Time after exposure period started
Hours*
 0.5  1.0  1.5  2.0  2.5  3.0  3.5  4.0  4.5  5.0  5.5  6.0  24  48  72

Males

Piloerection (s-e)  5  5  5  5  5  5  **  **  10  10  10  0  0  0  0
Acitivty decreased (s)  0  5  5  5  5  5  **  **  10  10  0  0  0  0  0
Ptosis (s)  0  5  5  5  5  5  **  **  0  0  0  0  0  0  0

Females

Piloerection (s-e)   5  5  5  5  5  5  **  **  10  10  10  10  0  0  0
Activity decreased (s)   0  5  5  5  5  5  **  **  10  10  10  0  0  0  0
Ptosis (s)   0  5  5  5  5  5  **  **  0  0  0  0  0  0  0

Severity signs: v-very slight, s-slight, m-moderate, e-extreme (no details provided regarding severity ranking in the exposed animals)

*- Due to chamber design only ten animals (5 males, 5 females) could be observed during exposure period.

**- Unable to observe animals at this point due to excessive collection of test material of the chamber window.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions of this study, the inhalatory LC50 value of Catapal Alumina Fines when administered undiluted as an aerosol for 4 hours in rats was considered to exceed 5 mg/L. Therefore, no classification is required according to Regulation (EC) No 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute inhalation toxicity study performed according to OECD Guideline 403 and in compliance with GLP, ten male and ten female rats were exposed for four hours to an aerosol generated from the undiluted test material (fine powder) at an exposure concentration of 5.09 mg/L or 5,090 mg/m3. Twenty animals (negative control group) were housed in the same manner in an identical inhalation chamber for 4 hours without exposure to the test material. All animal were returned to their laboratory cages within 24 hours after termination of exposure. The actual exposure concentration of test material at the breathing zone of the animals was determined gravimetrically 2 times per hour. The mass median aerodynamic diameter (MMAD) for the Catapal Alumina fine powder particles (fine powder administered undiluted as an aerosol) was 4.64 microns (geometric standard deviation - 3.16 microns) (4 hours distribution data). Animals were then observed for mortality, clinical signs and body weights and were all sacrificed for macroscopic examination (Day 3). Nasal turbinate, lungs and trachea from all Al exposed and control group animals were removed, fixed in 10% neutral buffered formalin for microscopic histopathology examination.

 

No mortality was observed. Clinical signs of piloerection were noted in male and female rats during exposure period and in all males and females during 1.5 hours and 2.0 hours post administration, respectively. Decreased activity was observed in the treated male and female rats during exposure period and 1.0 hour and 1.5 hours post administration, respectively. Ptosis was observed in the treated male and female rats during exposure period only. All animals appeared to be normal and no toxic signs were observed at 24, 48 and 72 hours post administration. No body weight changes were noted during the post-exposure observation period. Macroscopic examination at the end of the 24 and 72 observation periods did not reveal any aluminium-related changes of the internal organs of the treated animals compared to the control group. The results showed no histopathological changes in the nasal turbinate, trachea and lungs of the Catapal Alumina exposed animals.

Under the test conditions of this study, the inhalatory LC50, 4h value of (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.

 

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
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.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: - JMAFF, 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
Principles of method if other than guideline:
Not applicable.
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Crl:WI(Han)
Sex:
male/female
Details on test animals 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
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle).
Mass median aerodynamic diameter (MMAD):
>= 4 - <= 5 mm
Geometric standard deviation (GSD):
1.7
Remark on MMAD/GSD:
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.
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:
no
Details on study design:
The test substance 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.
Preliminary study:
Not applicable.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 mg/L air
Based on:
test mat.
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.

None.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the inhalatory LC50, 4h value of 202028/A (aerosol) in rats was considered to exceed 5 mg/L. Therefore, no classification is required according to Regulation (EC) No 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute inhalation toxicity study performed according to OECD Guideline 403 and in compliance with GLP, groups (5/sex/dose) of Wistar rats were given 202028/Aas an aerosol by inhalation for 4 hours at 6.1 ± 1.8 mg/L of the neat test substance (correction factor 3.7 for the evaporable water content).

Animals were then observed for mortality, clinical signs and body weights for 14 days and were all sacrificed for macroscopic examination (Day 15).  

  

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 other 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.

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.

 

Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Common precursor(s)/breakdown product(s): Al3+ is the substance of biological interest and that the toxicological effects of Aluminium sulphate can be attributed exclusively to Al3+.

2. SOURCE AND TARGET CHEMICAL(S)
Source substance: Aluminum chloride hydroxide sulfate (CAS No 3290-78-3)
Target substance: Aluminium sulphate hydrated (CAS No 17927-65-0)

3. ANALOGUE APPROACH JUSTIFICATION
Based on the similar behaviour regarding toxicokinetics, data from the different soluble Aluminium salts are used in read-across approach to assess the toxicological properties of Aluminium sulphate. Hence, the data from the other soluble Aluminium salts are considered as a starting point in the hazard assessment of Aluminium sulphate taking into account the differences in bioavailability using available toxicokinetic information.

4. DATA MATRIX
See attached justification
Reason / purpose:
read-across source
Mass median aerodynamic diameter (MMAD):
>= <=
Preliminary study:
Not applicable.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 mg/L air
Based on:
test mat.
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.

None.

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the read-across approach, the inhalatory LC50, 4h value of the target substance (aerosol) in rats was considered to exceed 5 mg/L. Therefore, no classification is required according to Regulation (EC) No 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute inhalation toxicity study performed according to OECD Guideline 403 and in compliance with GLP, groups (5/sex/dose) of Wistar rats were given 202028/Aas an aerosol by inhalation for 4 hours at 6.1 ± 1.8 mg/L of the neat test substance (correction factor 3.7 for the evaporable water content).

Animals were then observed for mortality, clinical signs and body weights for 14 days and were all sacrificed for macroscopic examination (Day 15).  

  

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 other 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.

Based on the read-across approach, the inhalatory LC50, 4h value of the target substance 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.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 000 mg/m³
Quality of whole database:
Studies performed similarly to OECD guideline 403 with Klimisch rate of 1 or 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
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:
GHS criteria not met
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. Therefore the test material was not classified according to Regulation EC No.1272/2008 (CLP) and to the GHS.
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. Therefore the registered substance was not classified according to the Annex VI of the Regulation EC No.1272/2008 (CLP) and to the GHS.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
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 1 or 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 classification or non-classification

Harmonized classification:

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

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 (CLP) as the LD50 is greater than 2000 mg/kg bw.

- classified in category 5 according to the GHS as the LD50 is greater than 2000 mg/kg bw and less than 5000 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 (CLP) and to the GHS 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 GHS.