Aluminium sulphate

Endpoint summary

Description of key information

Skin irritation 
-Based on the results of the study of Lansdown AB.1973, it was concluded that Aluminum sulphate, anhydrous induced no skin irritation, so the test material is classified as non-irritant to the skin according to EU.
No epidermal and pathological changes and dermal reactions were observed with aluminium sulphate treatment up to 233.5  mg/kg bw
-Based on the results of the Toxicology lab report T-4874 regarding primary dermal and eye irritation of aluminum sulfate it was concluded that Aluminum sulphate induced no skin irritation, so the test material is classified as non-irritant to the skin according to OECD-GHS.
Eye irritation 
-Based on the results of Toxicology lab report T-4874 regarding primary dermal and eye irritation of aluminum sulfate, it was concluded that the test compound, Aluminum sulfate hydrate, induced a moderate eye irritation. It is not known whether reversibility of the eye effects would occur, as the observation period is only up to 7 days after application. It seems, however, that reversibility will occur within 21 days so the test material is classified as moderately irritant to the skin according to EU.
-Based on the results of the study of Grekhova TD,et al 1994 , it was concluded that the test compound, Aluminum sulfate, induced a moderate  eye irritation. Instillation of aluminum sulfate into the eye results in conjunctivitis and purulent ophthalmitis. Aluminum sulfate and coagulants afflict the nervous system, liver and heart.
Respiratory irritation. 
-Based on the results of the study of Ichinose et al.2008 it was concluded that the test compound Aluminum sulfate, (the result was read across from aluminium oxide ) do not  induced a Respiratory irritation. No signs of irritation of respiratory tract and Nasal effects were observed in rats as reddish nasal discharge. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication which meets basic scientific principles

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

Three difference species of animals (mice, rabbit and white pigs) were used in an in vivo experiment to determine whether repeated, non-occlusive exposures to solutions or suspensions of different aluminium salts led to irritative effects on the skin. Skin samples were examined both macroscopically, microscopically in stained thin –section and histochemical techniques were employed to characterize the interaction of the aluminium with skin components.

GLP compliance:

not specified

Species:

other: 5 mice, 3 rabbits and 2 pigs

Strain:

other: mice: female, TF1 strain of the Carworth Farm Stock of albino mice; rabbits: New Zealand white strain from Norfolk Rabbits Ltd., Attleborough, Norfolk; pigs: large white stain

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Mice: female, TF1 strain of the Carworth Farm Stock of albino mice. The mice used were randomly selected and aged about 8 weeks.
Rabbits: New Zealand white strain from Norfolk Rabbits Ltd., Attleborough, Norfolk. The rabbits were aged about 6 months at the start of the experiment.
Pigs: large white strain. The pigs were aged about 6 months at the start of the experiment.

-Environmental/Housing conditions
.The animals were maintained on a strict daily routine of 18h light/6 hours dark

Type of coverage:

open

Preparation of test site:

shaved

Vehicle:

water

Controls:

yes

Amount / concentration applied:

Concentrations:
In experiment 1, aluminium chloride (anhydrous) was applied at concentrations of 2.5, 5, 10 and 25% w/v and aluminium chlorhydrate at concentrations of 10 and 25% w/v to mice.
In experiment 2, aluminium chloride, aluminium nitrate, aluminium sulphate, aluminium chlorhydrate, aluminium hydroxide and aluminium basic acetate were applied at concentrations of 10% w/v to groups of 5 mice, 3 rabbits and 2 pigs. Aluminium chlorhydrate was also tested at a concentration of 25%.

Volume:
0.5 mL was applied daily to a 2 cm² area on the backs of the mice and rabbits. 1.0 mL was applied daily to a 4 cm² area of the pigs’ skin.

Duration of treatment / exposure:

5 days; (5 daily applications).

Observation period:

The animals were killed 24 hours after the final treatment. The mice were killed by cervical dislocation and the rabbits and pigs by an overdose of pentabarbital (Nembutal).

Number of animals:

5 mice, 3 rabbits and 2 pigs

Details on study design:

TEST SITE
- Area of exposure: the test solutions were applied and then spread out using clean glass rods to cover areas of 2cm2 of skin for mice and rabbits and 4cm2 for pigs.
- Type of wrap if used: the test areas were not covered.
For microscopic examination (fluorescence microscopy and ordinary light microscopy), samples of treated skin were fixed in 70% ethanol for at least 18h, embedded in paraffin wax and sectioned at 5-7μm for staining with haematoxylin and eosin. Morin (dye) was used to determine the presence of aluminium (Pearse, 1960); the congo red/thioflavine T technique (Jarrett et al., 1959) was used for epidermal keratins, the DDD technique (Barrnett & Seligman, 1952) for protein-bound sulphydryl groups and Baker’s method (1944) was used for examining epidermal phospholipids.

The pH of the test solutions were measured although details of the measurement method were not provided.

Additional informations to the control animals:
A negative control group received applications of distilled water.
Previous studies were referenced as evidence for the lack of irritative effects of the 0.2% Tween-80 vehicle used for the aluminium hydroxide and the basic aluminium acetate.
A series of “hydrochloric acid” control groups (5 mice per group) received administrations of dilute solutions of hydrochloric acid with pH values of 2.2, 3.0 and 4.0.

Another series of control groups (5 mice per group) received administrations of solutions of Universal buffer with pH of 2.5, 3.1, 3.4 or 4.0.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 5 days

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: No epidermal and pathological changes and dermal reactions were observed with aluminium sulphate treatment up to 233.5 mg/kg bw

Irritant / corrosive response data:

No epidermal and pathological changes and dermal reactions were observed with aluminium sulphate treatment up to 233.5 mg/kg bw

The results were adequately described and informative due to the use of macroscopic and microscopic techniques, and also histochemical methods to characterize the changes that had taken place at a molecular level.

Interpretation of results:

not irritating

Remarks:

Migrated information No epidermal and pathological changes and dermal reactions were observed with aluminium sulphate treatment up to 233.5 mg/kg bw Criteria used for interpretation of results: EU

Conclusions:

Based on the results of the present study, it was concluded that Aluminum sulphate, anhydrous induced no skin irritation, so the test material is classified as non-irritant to the skin according to EU.
No epidermal and pathological changes and dermal reactions were observed with aluminium sulphate treatment up to 233.5 mg/kg bw

Executive summary:

The responses of mouse, rabbit and pig skin to topically applied solutions of six aluminium salts (aluminium chloride, aluminium nitrate,aluminium sulphate,aluminium hydroxide, aluminium acetate and aluminium chlorhydrate) have been studied in relation to their pH and the deposition of aluminium in the stratum corneum.

 Epidermal changes consisting of hyperplasia, microabscess formation, dermal inflammatory cell infiltration and occasionally ulceration were evident in all three species treated with aluminium chloride (10%) and nitrate (10%),but not with aluminium sulphate (10%),hydroxide (10%), acetate (10%) or chlorhydrate (10 and 25%).

 In skins showing pathological changes, a high degree of aluminium deposition was present in the stratum corneum and the keratin was histochemically abnormal. It contained an unusually high concentration of protein-bound sulphydryl groups and phospholipid, and fluoresced differently to normal with the congo red technique.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reliable with restrictions. Well-presented study, with relevant measurement of chemical concentrations

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS: Healthy New Zealand white rabbits weighing 2.5-3.0 kg
Rabbits are purchased from laboratory animal supplier.

Vehicle:

physiological saline

Controls:

yes

Amount / concentration applied:

0.5 mg/m3.

Duration of treatment / exposure:

21 days.

Observation period (in vivo):

21 days.

Number of animals or in vitro replicates:

6

Details on study design:

METHOD FOLLOWED: Determination of irritant/corrosive effects were examined using rabbits, according to OECD 405.
DEVIATIONS FROM GUIDELINE: no deviations reported
STATISTICAL METHODS: DRAIZE score system was used 
METHOD OF CALCULATION: not described
ANALYTICAL METHODS: not applied
TEST ANIMALS: Rabbits - Strain: HC:NZW 
- Sex: not described -
- Age: adults
- Weight at study initiation: not described 
- Number of animals: 6
- Controls: other eye
ADMINISTRATION/EXPOSURE 
- Preparation of test substance: Pulverized powder
- Amount of substance instilled:  0.5 mg/m3.
- Vehicle: not described
- Postexposure period: 21 days
- exposure : 24 hours
EXAMINATIONS - Ophtalmoscopic examination: yes
- Scoring system: DRAIZE system
- Observation period: 21 days
- Tool used to assess score: optical instrument (hand slit lamp)

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 7 days

Score:

1.3 - 2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Category 2B (mildly irritating to eyes)

Irritant / corrosive response data:

Instillation of aluminum sulfate into the eye results in conjunctivitis and purulent ophthalmitis. Aluminum sulfate and coagulants afflict the nervous system, liver and heart. The recommended MAC in the air of workplace for aluminum sulfate, is equal to 0.5 mg/m3.

Interpretation of results:

Category 2B (mildly irritating to eyes) based on GHS criteria

Remarks:

Migrated information

Conclusions:

Instillation of aluminum sulfate into the eye results in conjunctivitis and purulent ophthalmitis. Aluminum sulfate and coagulants afflict the nervous system, liver and heart. The recommended MAC in the air of workplace for aluminum sulfate, is equal to 0.5 mg/m3.

Executive summary:

Aluminum sulfate, potash alum, ammonium alum, purified and unpurified nephelinic coagulant are assigned to the 3rd jeopardy class (moderately dangerous chemicals), sodium alum-to the 4th jeopardy class (slightly dangerous chemicals) at the single exposure. Local irritation of rabbit's skin was not revealed, but instillation into the eye results in conjunctivitis and purulent ophthalmitis. Aluminum sulfate and coagulants afflict the nervous system, liver and heart. The recommended MAC in the air of workplace for aluminum sulfate, potash alum, sodium alum and coagulants based on them is equal to 0.5 mg/m3.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

 Skin irritation

 -Based on the results of the study of Lansdown AB.1973, it was concluded that Aluminum sulphate, anhydrous induced no skin irritation, so the test material is classified as non-irritant to the skin according to EU.

No epidermal and pathological changes and dermal reactions were observed with aluminium sulphate treatment up to 233.5 mg/kg bw

-Based on the results of the Toxicology lab report T-4874 regarding primary dermal and eye irritation of aluminum sulfate it was concluded that Aluminum sulphate induced no skin irritation, so the test material is classified as non-irritant to the skin according to OECD-GHS.

 

Eye irritation

 -Based on the results of Toxicology lab report T-4874 regarding primary dermal and eye irritation of aluminum sulfate, it was concluded that the test compound, Aluminum sulfate hydrate, induced a moderate eye irritation. It is not known whether reversibility of the eye effects would occur, as the observation period is only up to 7 days after application. It seems, however, that reversibility will occur within 21 days so the test material is classified as moderately irritant to the skin according to EU.

 -Based on the results of the study of Grekhova TD,et al 1994 , it was concluded that the test compound, Aluminum sulfate, induced a moderate eye irritation.Instillation of aluminum sulfate into the eye results in conjunctivitis and purulent ophthalmitis. Aluminum sulfate and coagulants afflict the nervous system, liver and heart.

 

 Respiratory irritation.

-Based on the results of the study ofIchinose et al.2008 it was concluded that the test compound Aluminum sulfate,(the result was read across fromaluminium oxide) do not induced aRespiratory irritation.No signs of irritation of respiratory tract and Nasal effects were observed in rats as reddish nasal discharge.

Effects on eye irritation: moderately irritating

Justification for classification or non-classification

Based on the hazard assessment of aluminium sulphate in section 2.1 and 2.2.in IUCLID 5.4., available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health” andaccording to the criteria described in Directive 67/548 and in the CLP Regulation:

 

Directive 67/548	Skin Corrosivity C R35 Causes severe burns R34 Causes burns Skin Irritation Xi R38 Irritating to skin R43 May cause sensitization by skin contact Eye Irritation (Ocular Lesions) Xi R36 Irritating to eyes R41 Risk of serious damage to eyes
CLP	Skin Corrosivity  H314 Skin Corr 1A Causes severe skin burns and eye damage H314 Skin Corr 1B Causes severe skin burns and eye damage Skin Irritation  H315 Skin Irrit. 2 Causes skin irritation H317 Skin Sens. 1 May cause an allergic skin reaction Eye Irritation (Ocular Lesions) Xi H319 Eye Irrit. 2 Causes serious eye irritation H318 Eye Dam. 1 Causes serious eye damage

 

 

It is concluded that the substance aluminium sulphate meet the criteria to be classified for human health hazards for Dermal-local effect:R41 Risk of serious damage to eyes, Eye Damage 1, H318: Causes serious eye damage.