Aluminium sulphate

Repeated dose toxicity: dermal

Administrative data

Endpoint:

chronic toxicity: dermal

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reliable with restrictions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OTS 798.3260 (Chronic Toxicity)

GLP compliance:

not specified

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Aluminium chloride

EC Number:

231-208-1

EC Name:

Aluminium chloride

Cas Number:

7446-70-0

IUPAC Name:

aluminum trichloride

Details on test material:

Name of test material :other aluminium chloride

Name of test material: aluminium chloride
-CAS №7446-70-0
-EC № 231-208-1
- Molecular formula : AlCl3
- Molecular weight: 133.34 g/mol (anhydrous), 241.43 g/mol (hexahydrate)
- Smiles notation: Cl[Al](Cl)Cl
- InChl : 1/Al.3ClH/h;3*1H/q+3;;;/p-3
- Structural formula attached as image file: see Fig.1
- Substance type:inorganic
- Physical state: white or pale yellow solid, hygroscopic
- Odor: odorless
- Density: 2.48 g/cm3 (anhydrous), 1.3 g/cm3 (hexahydrate
- Melting point: 192.4 °C *(anhydrous), 0 °C (hexahydrate)
- Solubility in water:
43.9 g/100 ml (0 °C)
44.9 g/100 ml (10 °C)
45.8 g/100 ml (20 °C)
46.6 g/100 ml (30 °C)
47.3 g/100 ml (40 °C)
48.1 g/100 ml (60 °C)
48.6 g/100 ml (80 °C)
49 g/100 ml (100 °C)

-Solubility : soluble in hydrogen chloride, ethanol, chloroform, carbon tetrachloride, slightly soluble in benzene

Test animals

Species:

mouse

Strain:

Swiss

Sex:

female

Administration / exposure

Type of coverage:

open

Vehicle:

water

Details on exposure:

In this study was applied 20 μL of a 0.025 or 0.1 μg aluminium chloride/mL solution to 4 cm2 of skin (0.1 and 0.4 μg/day) on the dorsal shaved surface of mice for 130 days. The total aluminium applied during this time (0.5 to 2 mg/kg) is comparable to a one day aluminium exposure of humans using topical antiperspirants.
Twenty-four hr urine samples were obtained starting 1 day after completion of aluminium dosing. Blood and brain samples were also obtained. A statistically significant increase was reported in urinary and serum aluminium concentrations after both aluminium exposures, compared to those for non-exposed mice of the same age. This suggests that a small fraction of the typical human use of a topical antiperspirant might produce a measurable increase in urine and tissue aluminium levels.
Dermal exposure of mice pups from 2 to 22 days of age to 0.025, 0.05 or 0.1 μg aluminium chloride/cm2 increased their brain aluminium levels by 5 to 24%. Using X-ray energy scanning electron microscopy, the authors reported 11 to 120-fold more aluminium in the hippocampus of treated mice than in those of controls, whereas atomic absorption spectrometric analysis of aluminium showed a 1.6 to 2.2-fold increase.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

130 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
20 μL of a 0.025 or 0.1 μg aluminium chloride/mL solution to 4 cm2 of skin (0.1 and 0.4 μg/day)
Basis:
nominal per unit area

No. of animals per sex per dose:

nr

Control animals:

yes

Details on study design:

20 μL of a 0.025 or 0.1 μg aluminium chloride/mL solution was applied to 4 cm2 of skin (0.1 and 0.4 μg/day) on the dorsal shaved surface of mice for 130 days. The total aluminium applied during this time (0.5 to 2 mg/kg) is comparable to a one day aluminium exposure of humans using topical antiperspirants.
Twenty-four hr urine samples were obtained starting 1 day after completion of aluminium dosing. Blood and brain samples were also obtained. A statistically significant increase was reported in urinary and serum aluminium concentrations after both aluminium exposures, compared to those for non-exposed mice of the same age. This suggests that a small fraction of the typical human use of a topical antiperspirant might produce a measurable increase in urine and tissue aluminium levels.
Dermal exposure of mice pups from 2 to 22 days of age to 0.025, 0.05 or 0.1 μg aluminium chloride/cm2 increased their brain aluminium levels by 5 to 24%.

Examinations

Observations and examinations performed and frequency:

20 μL of a 0.025 or 0.1 μg aluminium chloride/mL solution was applied to 4 cm2 of skin (0.1 and 0.4 μg/day) on the dorsal shaved surface of mice for 130 days. The total aluminium applied during this time (0.5 to 2 mg/kg) is comparable to a one day aluminium exposure of humans using topical antiperspirants.
Twenty-four hr urine samples were obtained starting 1 day after completion of aluminium dosing. Blood and brain samples were also obtained. A statistically significant increase was reported in urinary and serum aluminium concentrations after both aluminium exposures, compared to those for non-exposed mice of the same age. This suggests that a small fraction of the typical human use of a topical antiperspirant might produce a measurable increase in urine and tissue aluminium levels.
Increases in brain aluminium levels were 19 to 124% over controls. The aluminium concentration in the hippocampus was reported to be 2 to 3 times the rest of the brain in controls and aluminium-exposed mice. This could be an artifact of aluminium contamination, which would be more pronounced in a smaller sample (hippocampus) than in the rest of the brain.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

Dermal exposure of mice pups from 2 to 22 days of age to 0.025, 0.05 or 0.1 μg aluminium chloride/cm2 increased their brain aluminium levels by 5 to 24%. Using X-ray energy scanning electron microscopy, the authors reported 11 to 120-fold more aluminium in the hippocampus of treated mice than in those of controls, whereas atomic absorption spectrometric analysis of aluminium showed a 1.6 to 2.2-fold increase.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Dermal irritation:

no effects observed

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

effects observed, treatment-related

Behaviour (functional findings):

effects observed, treatment-related

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

effects observed, treatment-related

Details on results:

No adverse effects observed below 3.17 (NOAEL)
The total applied dose was 0.5 Al mg/kg bw or 3.17 mg/kg bw as aluminium sulphate.
increased levels of aluminum in the urine of mice exposed above 3.17mg/kg bw (total) applied daily to a 4 cm2 shaved area for 130 days.
Increases in brain aluminium levels were 19 to 124% over controls. The aluminium concentration in the hippocampus was reported to be 2 to 3 times the rest of the brain in controls and aluminium-exposed mice.
Dermal exposure of mice pups from 2 to 22 days of age increased their brain aluminium levels by 5 to 24%.
No adverse effects observed below 0.79 (NOAEL)
Using X-ray energy scanning electron microscopy, the authors reported 11 to 120-fold more aluminium in the hippocampus of treated mice than in those of controls, whereas atomic absorption spectrometric analysis of aluminium showed a 1.6 to 2.2-fold increase.

Effect levels

1

Dose descriptor:

NOAEL

Remarks:

adult mice

Effect level:

3.17 mg/kg bw (total dose)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: overall effects No adverse effects observed The total applied dose was 0.5 Al mg/kg bw or 3.17 mg/kg bw as aluminium sulphate

2

Dose descriptor:

LOAEL

Remarks:

adult mice

Effect level:

12.66 mg/kg bw (total dose)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: see 'Remark'

3

Dose descriptor:

NOAEL

Remarks:

mice pups from 2 to 22 days of age

Effect level:

0.79 mg/kg bw (total dose)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: overall effects No adverse effects observed The total applied dose was 0.125 Al mg/kg bw or 0.79 mg/kg bw as aluminium sulphate

4

Dose descriptor:

NOAEL

Remarks:

mice pups from 2 to 22 days of age

Effect level:

3.17 mg/kg bw (total dose)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Anane et al. (1995) applied 20 μL of a 0.025 or 0.1 μg aluminium chloride/mL solution to 4 cm2 of skin (0.1 and 0.4 Al μg/day) on the dorsal shaved surface of mice for 130 days. The total aluminium applied during this time (0.5 to 2 Almg/kg) is comparable to a one day aluminium exposure of humans using topical antiperspirants.

Twenty-four hr urine samples were obtained starting 1 day after completion of aluminium dosing. Blood and brain samples were also obtained. A statistically significant increase was reported in urinary and serum aluminium concentrations after both aluminium exposures, compared to those for non-exposed mice of the same age. This suggests that a small fraction of the typical human use of a topical antiperspirant might produce a measurable increase in urine and tissue aluminium levels.

Increases in brain aluminium levels were 19 to 124% over controls. The aluminium concentration in the hippocampus was reported to be 2 to 3 times the rest of the brain in controls and aluminium-exposed mice. This could be an artifact of aluminium contamination, which would be more pronounced in a smaller sample (hippocampus) than in the rest of the brain.

 Dermal exposure of mice pups from 2 to 22 days of age to 0.025, 0.05 or 0.1 μg aluminium chloride/cm2 increased their brain aluminium levels by 5 to 24%. Using X-ray energy scanning electron microscopy, the authors reported 11 to 120-fold more aluminium in the hippocampus of treated mice than in those of controls, whereas atomic absorption spectrometric analysis of aluminium showed a 1.6 to 2.2-fold increase.

 Absorption of aluminium, applied as aluminium chloride, to mouse skin in vitro, was determined in a “static” culture system. Increased aluminium was observed in the compartment that modelled sub-dermal fluid.

Applicant's summary and conclusion

Conclusions:

No adverse effects observed below 3.17 (NOAEL)
The total applied dose was 0.5 Al mg/kg bw or 3.17 mg/kg bw as aluminium sulphate.
increased levels of aluminum in the urine of mice exposed above 3.17mg/kg bw (total) applied daily to a 4 cm2 shaved area for 130 days.
Increases in brain aluminium levels were 19 to 124% over controls. The aluminium concentration in the hippocampus was reported to be 2 to 3 times the rest of the brain in controls and aluminium-exposed mice.
Dermal exposure of mice pups from 2 to 22 days of age increased their brain aluminium levels by 5 to 24%.
No adverse effects observed below 0.79 (NOAEL)

Executive summary:

 20 μL of a 0.025 or 0.1 μg aluminium chloride/mL solution was applied to 4 cm2 of skin (0.1 and 0.4 μg/day) on the dorsal shaved surface of mice for 130 days. The total aluminium applied during this time (0.5 to 2 mg/kg) is comparable to a one day aluminium exposure of humans using topical antiperspirants.

Twenty-four hr urine samples were obtained starting 1 day after completion of aluminium dosing. Blood and brain samples were also obtained. A statistically significant increase was reported in urinary and serum aluminium concentrations after both aluminium exposures, compared to those for non-exposed mice of the same age. This suggests that a small fraction of the typical human use of a topical antiperspirant might produce a measurable increase in urine and tissue aluminium levels.

Increases in brain aluminium levels were 19 to 124% over controls. The aluminium concentration in the hippocampus was reported to be 2 to 3 times the rest of the brain in controls and aluminium-exposed mice. This could be an artifact of aluminium contamination, which would be more pronounced in a smaller sample (hippocampus) than in the rest of the brain.

 Dermal exposure of mice pups from 2 to 22 days of age to 0.025, 0.05 or 0.1 μg aluminium chloride/cm2 increased their brain aluminium levels by 5 to 24%. Using X-ray energy scanning electron microscopy, the authors reported 11 to 120-fold more aluminium in the hippocampus of treated mice than in those of controls, whereas atomic absorption spectrometric analysis of aluminium showed a 1.6 to 2.2-fold increase.

 Absorption of aluminium, applied as aluminium chloride, to mouse skin in vitro, was determined in a “static” culture system. Increased aluminium was observed in the compartment that modelled sub-dermal fluid.