Aluminium sulphate

Endpoint summary

Description of key information

- Acute oral toxicity:The LD50 value from 4618 mg/kg  bw to 6200 mg/kg bw  in mouse were determined for Aluminium sulphate. This show that Aluminium sulphate  has of relatively low acute toxicity of acute oral toxicity. The acute oral median lethal dose to rats of Aluminum sulphate was found to be greater than 5000 mg/kg bodyweight for males and females. 
-Acute Dermal Toxicity: An LD50 value of > 1167.5 mg/kg was obtained. No epidermal and pathological changes and dermal reactions were observed with aluminium sulphate treatment up to 233.5 mg/kg bw. This show  that Aluminium sulphate is not classified for  acute Dermal toxicity .
- Acute  inhalation toxicity :Based on the results of thе study (Thomson SM,. 1986), the LC50 for Acute inhalation toxicity of Aluminium sulphate  obtained was >50 mg/m³ air .
It is concluded that the substance Aluminium sulphate does  meet the criteria to be classified for human health hazards for acute oral, dermal  and inhalation effects.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Reliable without restrictions. Well-presented study, with relevant measurement of chemical concentrations

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

no

Species:

mouse

Strain:

Swiss

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Exposure Duration Frequency:The test item was administered in a single dose by gavage and intraperitoneally

No. of animals per sex per dose:

20

Control animals:

yes

Details on study design:

Four aluminum compounds--nitrate, chloride, sulphate and bromide--were administered orally and intraperitoneally to rats and mice. The LD50-values (14 days) were determined. The majority of deaths occurring during the first four days.

Preliminary study:

Four aluminum compounds--nitrate, chloride, sulphate and bromide--were administered orally and intraperitoneally to rats and mice. The LD50-values (14 days) were determined. The majority of deaths occurring during the first four days.
The clinical and physical signs appearing after intoxication include among other lethargy, decreased locomotor activity, piloerection, weight loss and perorbital bleeding. Aluminum concentrations were highest in liver and spleen. No histopathological lesions could be observed.
According to an acute oral toxicity test conducted with aluminium sulphate it can be stated that the substances shows low orally toxic characteristic.The oral LD50 in Mouse (Swiss) was determined to be above 4618 mg/kg body weight or above 730 mg Al/kg bw.
The intraperitoneally LD50 in Mouse (Swiss) was determined to be 253 mg/kg bw or 40 mg Al/kg body weight.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 4 618 mg/kg bw

Based on:

test mat.

Remarks on result:

other: The intraperitoneally LD50 in Mouse (Swiss) was determined to be 253 mg/kg bw or 40 mg Al/kg body weight.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

253 mg/kg bw

Based on:

test mat.

Remarks:

intraperitoneally

Mortality:

The majority of deaths occurring during the first four days.

Clinical signs:

other: The clinical and physical signs appearing after intoxication include among other lethargy, decreased locomotor activity, piloerection, weight loss and perorbital bleeding.

Gross pathology:

After 14 days no alterations in liver and renal functions were detected in the animals which received intraperitoneally the LD50-values of aluminum nitrate as a single dose.

Other findings:

Aluminum concentrations were highest in liver and spleen. No histopathological lesions could be observed.

Interpretation of results:

sligthly toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to an acute oral toxicity test conducted with aluminium sulphate it can be stated that the substances shows low orally toxic characteristic.The oral LD50 in Mouse (Swiss) was determined to be above 4618 mg/kg body weight or above 730 mg Al/kg bw.
The intraperitoneally LD50 in Mouse (Swiss) was determined to be 253 mg/kg bw or 40 mg Al/kg body weight.

Executive summary:

Four aluminum compounds--nitrate, chloride, sulphate and bromide--were administered orally and intraperitoneally to rats and mice. The LD50-values (14 days) were determined. The majority of deaths occurring during the first four days.

The clinical and physical signs appearing after intoxication include among other lethargy, decreased locomotor activity, piloerection, weight loss and perorbital bleeding.

After 14 days no alterations in liver and renal functions were detected in the animals which received intraperitoneally the LD50-values of aluminum nitrate as a single dose. Aluminum concentrations were highest in liver and spleen. No histopathological lesions could be observed. To compare the efficacies of nine chelating agents on the toxicity of aluminum in mice, the therapeutic index and the therapeutic effectiveness of each chelating agent have been calculated. Malic, succinic, oxalic and malonic acids showed the best results with malic and succinic acids being the most effective. Deferoxamine mesylate (DFOA), sodium salicylate, L-cysteine and citric acid were not so effective as antidotes for acute aluminum toxicity. Aurin tricarboxylic acid (ATCA) should not be used due to its high toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 618 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Reliable without restrictions. Well-presented study, with relevant measurement of chemical concentrations

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Fischer 344

Sex:

male

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: lavage fluid

Details on inhalation exposure:

Groups of male, Fischer 344 rats were exposed 4 h to one of five dosage levels of aluminum (1000, 200, 100, 50, 10 mg m-3).
At 24 h, 14 days and 3 months post-exposure (PE), rats were evaluated for physiological and histological alterations to correlate with enzymatic and cytological profiles of lavage fluid.
At 24 h PE, there were dose-related increases in lactate dehydrogenase and protein in lavage fluid of the brass exposed rats, acute inflammatory response in terminal airways, increases in macrophages and neutrophils, and increased pulmonary resistance.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

5 d

Concentrations:

aluminum (1000, 200, 100, 50, 10 mg/ m3).

No. of animals per sex per dose:

Groups of male, Fischer 344 rats

Control animals:

yes

Details on study design:

Bronchopulmonary lavage has been used as a rapid screening test for acute lung injury from many pneumotoxic chemicals.
We demonstrated the efficacy of lavage fluid analysis for detection of acute pulmonary damage from inhaled metal dusts.
Groups of male, Fischer 344 rats were exposed 4 h to one of five dosage levels of aluminum (1000, 200, 100, 50, 10 mg m-3).
At 24 h, 14 days and 3 months post-exposure (PE), rats were evaluated for physiological and histological alterations to correlate with enzymatic and cytological profiles of lavage fluid.
At 24 h PE, there were dose-related increases in lactate dehydrogenase and protein in lavage fluid of the brass exposed rats, acute inflammatory response in terminal airways, increases in macrophages and neutrophils, and increased pulmonary resistance.
All reactions were resolved by 14 days PE. In contrast, aluminum powder produced no alteration in pulmonary function, but elicited persistent changes in enzymatic and cytological lavage fluid parameters with multifocal microgranulomas in lungs and hilar lymph nodes. Bronchopulmonary lavage analysis was useful as an indicator of inhalation hazards of brass and aluminum powders.

Preliminary study:

In rats exposed to aluminum flakes for 5 days, there were alterations in the cytological (increase in the number of polymorphonuclear neutrophils [PMNs]) and enzymatic (increased activity of alkaline phosphatase and lactate dehydrogenase) content of the lavage fluid at ≥50mg Al/m3 and multifocal microgranulomas in the lungs and hilar lymph nodes at ≥200 mg Al/m3 The enzymatic changes in the lavage fluid probably resulted from the presence of PMNs, increased phagocytosis of alveolar macrophages, and Type II cell hyperplasia.

Sex:

male

Dose descriptor:

other: NOAEL

Effect level:

10 mg/m³ air

Based on:

test mat.

Exp. duration:

5 d

Remarks on result:

other: no effect observed

Sex:

male

Dose descriptor:

LC50

Effect level:

50 mg/m³ air

Based on:

test mat.

Exp. duration:

5 d

Remarks on result:

other: increased lactate dehydrogenase, glucose- 6-phosphate dehydrogenase, and alkaline phosphatase activity in lavage fluid

Sex:

male

Dose descriptor:

LC50

Effect level:

200 mg/m³ air

Based on:

test mat.

Exp. duration:

5 d

Remarks on result:

other: multifocal microgranulomas in lungs

Mortality:

no

Clinical signs:

other: At 24 h, 14 days and 3 months post-exposure (PE), rats were evaluated for physiological and histological alterations to correlate with enzymatic and cytological profiles of lavage fluid. At 24 h PE, there were dose-related increases in lactate dehydrogen

Body weight:

no

Gross pathology:

multifocal microgranulomas in lungs at 200 mg/m3 air

Interpretation of results:

sligthly toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In rats exposed to aluminum suifate flakes for 5 days, there were alterations in the cytological (increase in the number of polymorphonuclear neutrophils [PMNs]) and enzymatic (increased activity of alkaline phosphatase and lactate dehydrogenase) content of the lavage fluid at ≥50mg Al/m3 and multifocal microgranulomas in the lungs and hilar lymph nodes at ≥200 mg Al/m3 The enzymatic changes in the lavage fluid probably resulted from the presence of PMNs, increased phagocytosis of alveolar macrophages, and Type II cell hyperplasia.

Executive summary:

Bronchopulmonary lavage has been used as a rapid screening test for acute lung injury from many pneumotoxic chemicals. We demonstrated the efficacy of lavage fluid analysis for detection of acute pulmonary damage from inhaled metal dusts. Groups of male, Fischer 344 rats were exposed 4 h to one of five dosage levels of either brass (200, 100, 50, 10, 1 mg m-3) or aluminum (1000, 200, 100, 50, 10 mg m-3). At 24 h, 14 days and 3 months post-exposure (PE), rats were evaluated for physiological and histological alterations to correlate with enzymatic and cytological profiles of lavage fluid. At 24 h PE, there were dose-related increases in lactate dehydrogenase and protein in lavage fluid of the brass exposed rats, acute inflammatory response in terminal airways, increases in macrophages and neutrophils, and increased pulmonary resistance. All reactions were resolved by 14 days PE. In contrast, aluminum powder produced no alteration in pulmonary function, but elicited persistent changes in enzymatic and cytological lavage fluid parameters with multifocal microgranulomas in lungs and hilar lymph nodes. Bronchopulmonary lavage analysis was useful as an indicator of inhalation hazards of brass and aluminum powders.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

50 mg/m³ air

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Reliable without restrictions. Guideline study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

female

Details on test animals or test system and environmental conditions:

Groups of 5 mice, 3 rabbits and 2 pigs were treated daily for 5 consecutive days with applications of 10 % w/v aluminium chloride, aluminium nitrate, aluminium chlorhydrate, aluminium sulphate, aluminium hydroxide (the pH of the solution was highest at 7.2 among these chemical species of Al tested) or basic aluminium acetate.

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

Skin damage has been observed in female TF1 Carworth mice, New Zealand rabbits, and Large White pigs following the application of 10% aluminum chloride (0.005–0.1 g Al) or aluminum nitrate (0.006– 0.013 g Al) for 5 days; but not from aluminum sulfate, hydroxide, acetate, or chlorhydrate (Lansdown 1973). The damage consisted of hyperplasia, microabscess formation, dermal inflammatory cell infiltration, and occasional ulceration.
These results suggest that the development of adverse dermal effects from exposure to aluminum depends upon its chemical form.

Duration of exposure:

5 days

Doses:

233.5 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

yes

Details on study design:

Skin damage has been observed in female TF1 Carworth mice, New Zealand rabbits, and Large White pigs following the application of 10% aluminum chloride (0.005–0.1 g Al) or aluminum nitrate (0.006– 0.013 g Al) for 5 days; but not from aluminum sulfate, hydroxide, acetate, or chlorhydrate (Lansdown 1973). The damage consisted of hyperplasia, microabscess formation, dermal inflammatory cell infiltration, and occasional ulceration.
These results suggest that the development of adverse dermal effects from exposure to aluminum depends upon its chemical form.

Preliminary study:

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%).

Sex:

female

Dose descriptor:

other: NOAEL

Effect level:

> 233.5 mg/kg bw

Based on:

test mat.

Remarks:

The application of 10% aluminum sulphate (0.1 g Al) is equivalent to 100 mgAl/l or 633 mg/l aluminium sulphate. For conversion in mg/kg we have divided to the density of aluminum sulphate (2.71) 633/2.71=233.5 mg/kg

Remarks on result:

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

Sex:

female

Dose descriptor:

LD50

Effect level:

> 1 167.5 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: None

Gross pathology:

None

Other findings:

None

 

The comparative irritancy of several aluminium salts was assessed by Lansdown (1973) in three different species. Groups of 5 mice, 3 rabbits and 2 pigs were treated daily for 5 consecutive days with applications of 10 % w/v aluminium chloride, aluminium nitrate, aluminium chlorhydrate, aluminium sulphate, aluminium hydroxide (the pH of the solution was highest at 7.2 among these chemical species of Al tested) or basic aluminium acetate. Twenty-four hr after the final treatment with aluminium hydroxide, signs of erythema, thickening, scaling hyperkeratosis, acanthosis, microabsecesses and the presence of aluminium in keratin were not observed. After single dermal application of aluminium hydroxide (10%) on mouse, rabbit and pig skin no signs of dermal irritation or inflammation were found (Lansdown, 1973).

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

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 acetateand 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.

 

Although the irritant aluminium solutions were more acid than the non-irritant salts, pH was not considered to be responsible since solutions of hydrochloric acid or Universal buffer having an equivalent pH were of negligible effect.

The results of this study indicate that as a result of an interaction of the aluminium cation with epidermal keratin, the latter becomes denatured and the stratum corneum is made more permeable.

The manifestation of pathological changes is attributed to the penetration of the aluminium salts through the stratum corneum and their toxic effects on the cells of the epiderm

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

1 167.5 mg/kg bw

Additional information

Oral exposure

 

In a study of oral and intraperitoneal administration during 14 days, Llobet et al. (1987) estimated the acute oral toxicity of aluminum chloride, nitrate and sulphate in Sprague-Dawley rats and Swiss mice.

The oral LD50 in Mouse (Swiss) was determined to be above 4618 mg/kg body weight or above 730 mg Al/kg bw.

Aluminum chloride and nitrate produced acute toxicities of similar magnitude (LD50of 222 to 370 mg Al/kg) in the mice and rats, whereas the toxicity of aluminum sulphate was considerably lower (LD50> 4618mg/kg in both species).

 

In an early review an LD50of apparently 6,200 mg /kg bw was reported for Al2(SO4)3 and of 3,850 mg Al/kg bw for Al(Cl)3administered to mice (R. Ondreička, et al. 1966).

 

 

Inhalation exposure

 

Based on the results of thе study (Thomson SM,.1986), the LC50 for Acute inhalation toxicity of Aluminium sulphateobtained was>50mg/m³ air.In rats exposed to aluminum suifate flakes for 5 days, there were alterations in the cytological (increase in the number of polymorphonuclear neutrophils [PMNs]) and enzymatic (increased activity of alkaline phosphatase and lactate dehydrogenase) content of the lavage fluid at ≥50mg Al/m3 and multifocal microgranulomas in the lungs and hilar lymph nodes at ≥200 mg Al/m3

 

In Golden Syrian hamsters and New Zealand rabbits exposed over a short duration (four to six hours per day for three to five days at levels of 7 to 200 mg/m3) to aluminum chlorohydrate through inhalation, the effects observed are those typically associated with inhalation of particulate matter, including alveolar wall thickening, increased number of macrophages and increased lung weight (ATSDR 2006).

 A more detailed discussion of the pulmonary effects in experimental animals of inhalation exposure to aluminum oxide dust and refractory alumina fibres, and aluminum hydroxide is provided by Krewski et al. (2007).

The observed responses to various species of aluminum are described as “typical of foreign body reaction”, including alveolar proteinosis and wall thickening, and some nodule formation.

 

Dermal exposure

 

Dermal effects of aluminum compounds (10% w/v chloride, nitrate, chlorohydrate, sulphate, hydroxide) applied to skin of mice, rabbits and pigs over five-day periods (once per day) include epidermal damage, hyperkeratosis, acanthosis and microabscesses (ATSDR 2006; Krewski et al. 2007).

An LD50 value of>1167.5mg/kg was obtained.No epidermal and pathological changes and dermal reactions were observed with aluminium sulphate treatment up to 233.5 mg/kg bw.This show that Aluminium sulphate is not classifiedfor acute Dermal toxicity .

 

 

 

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” and according to the criteria described in Directive 67/548 and in the CLP Regulation:

Directive 67/548

Very Toxic (T+) R28: Very toxic if swallowed R27: Very toxic in contact with skin R26: Very toxic by inhalation R39/26 R39/27 R39/28: Dangerous of very serious irreversible effects Toxic (T):  R25: Toxic if swallowed R24: Toxic in contact with skin R23: Toxic by inhalation R39/23 R39/24 R39/25: Danger of very serious irreversible effects Harmful (Xn): R22: Harmful if swallowed R21: Harmful in contact with skin R20: Harmful by inhalation R65: Harmful may cause lung damage if swallowed R68/20 R68/21 R68/22: Possible risk of irreversible effects Other toxicological properties R67: Vapours may cause drowsiness and dizziness

CLP

H300 Acute Tox. 2 Fatal if swallowed H310 Acute Tox. 1 Fatal in contact with skin H330 Acute Tox. 2 Fatal if inhaled H370 STOT SE 1 H301 Acute Tox. 3 Toxic if swallowed H311 Acute Tox. 3 Toxic in contact with skin H331 Acute Tox. 3 Toxic if inhaled H370 STOT SE 1 H302 Acute Tox. 4 Harmful if swallowed H312 Acute Tox. 4 Harmful in contact with skin H332 Acute Tox. 4 Harmful if inhaled H304 Asp. Tox. 1 H371 STOT SE 2 (May cause damage to organs (or state all organs affected if known) (state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard) Other toxicological properties H336 STOT SE 3 May cause drowsiness or dizziness

 

It is concluded that the substance aluminium sulphate does not meet the criteria to be classified for human health hazards for acute effects.