Aluminium sulphate

Endpoint summary

Description of key information

It is concluded that the substance Aluminium sulphate does not meet the criteria to be classified for human health hazards for Repeated  toxicity

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic 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 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 120-130 g
- Housing: Communally
- Diet (e.g. ad libitum): Ad libitum, standard rat chow
- Water (e.g. ad libitum): Ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25 degrees Celsius, controlled
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: drinking water

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Male Sprague Dawleyrats were given 0.3% aluminum sulfate (as 3.7% aluminum sulfate octadecahydrate solution) in drinking water for thirty days. During the last three weeks of aluminum sulfate administration, treated animals consumed 18 + or - 0.8 mL of aluminum sulfate solution/day/rat (2.0 mmoles of aluminum/day/rat) and controls consumed /about/ 28 mL of water/day/rat. Using a Lafayette passive avoidance device, an impairment of both consolidation and extinction of a passive avoidance task was seen in rats (n=4 to 10).
General motor activity was measured in an open field apparatus and a Lafayette step-up avoidance device was used for active avoidance tasks. To assess working memory in an appetitive task paradigm, a standard, wooden open eight-arm maze was used.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

30 days

Frequency of treatment:

Ad libitum

Remarks:

Doses / Concentrations:
0.3% aluminum sulfate (as 3.7% aluminum sulfate octadecahydrate solution) in drinking water
Basis:
nominal in water

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

Male Sprague Dawleyrats were given 0.3% aluminum sulfate (as 3.7% aluminum sulfate octadecahydrate solution) in drinking water for thirty days. During the last three weeks of aluminum sulfate administration, treated animals consumed 18 + or - 0.8 mL of aluminum sulfate solution/day/rat (2.0 mmoles of aluminum/day/rat) and controls consumed /about/ 28 mL of water/day/rat. Using a Lafayette passive avoidance device, an impairment of both consolidation and extinction of a passive avoidance task was seen in rats (n=4 to 10).
General motor activity was measured in an open field apparatus and a Lafayette step-up avoidance device was used for active avoidance tasks. To assess working memory in an appetitive task paradigm, a standard, wooden open eight-arm maze was used. No impairment of performance was observed on an active avoidance task (n=6, controls=4), radial arm maze (n=10, controls=4) or open field activity measure.

Positive control:

Not relevant

Observations and examinations performed and frequency:

Administration of aluminum sulfate in the drinking water of male Srpague-Dawley rats for 30 days resulted in a reduction in the number of days to reach extinction criterion on a passive avoidance task (38% control level). The behaviroal deficit was not due to nonspecific effects caused by lower fluid consumption. Partial reversal of the deficit was prduced by discontinuing aluminum treatment 2 weeks prior to testing (p<0.05). Injection of the aluminum chelator deferoxamine returned the performance of the aluminum treated animals to control levels in a dose dependent manner but had no effect on control animals.

Sacrifice and pathology:

BIOCHEMISTRY

- Choline acetyltransferase: measured using the method of Fonnum. Determination of ChAT activity in brain homogenates by scintillation counting of 14-C acetylchonline

- Muscarinic receptors: receptor binding in brain region homogenates measured using the method of Vickroy et al.

- Inositol phospholipid hydrolysis: phosphoinositide metabolism was determined by measurement of [3-H]myo-inositol-1-phosphate (M1P) accumulation using a modification of the method of Berridge et al. Metabolism was determined in both the lipid and aqueous phase of cortices/hippocampi (scintillation counting)

- Protein determination: Protein concentration was determined by the method of Lowry et al.

Statistics:

BEHAVIOUR:
- Activity: Student's t-test
- Passive avoidance: Fisher's exact test + ANOVA
- Active avoidance: ANOVA + Student's t-test
- Radial Arm Maze: Student's t-test + ANOVA

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

effects observed, treatment-related

Ophthalmological findings:

effects observed, treatment-related

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:

no effects observed

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:

Administration of aluminum sulfate in the drinking water of male Srpague-Dawley rats for 30 days resulted in a reduction in the number of days to reach extinction criterion on a passive avoidance task (38% control level). The behaviroal deficit was not due to nonspecific effects caused by lower fluid consumption. Partial reversal of the deficit was prduced by discontinuing aluminum treatment 2 weeks prior to testing (p<0.05). Injection of the aluminum chelator deferoxamine returned the performance of the aluminum treated animals to control levels in a dose dependent manner but had no effect on control animals.
No differenced in open field activity were evident across groups. These results indicate that the behavioral impairment is a specific, reversible, toxic effect of the aluminum administration.

Dose descriptor:

NOAEL

Effect level:

342 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: see 'Remark'

Critical effects observed:

not specified

Conclusions:

No differenced in open field activity were evident across groups. These results indicate that the behavioral impairment is a specific, reversible, toxic effect of the aluminum administration.

Executive summary:

Administration of aluminum sulfate in the drinking water of male Sprague-Dawley rats for thirty days resulted in an impairment of both consolidation and extinction of a passive avoidance task. No impairment of performance was observed on an active avoidance task, radial arm maze or open field activity measure. Biochemical analysis indicated a slight (less than 10%) but significant increase in hippocampal muscarinic receptor number after aluminum treatment as determined by tritiated quinuclidinyl benzilate (3H-QNB) binding. No changes were found in choline acetyltransferase (ChAT) activity, phosphoinositide hydrolysis, 3H-QNB binding in the cortex or tritiated pirenzepine (3H-PZ) binding in the hippocampus or cortex. These results indicate that cholinergic degeneration was not the cause of the observed cognitive impairments.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

342 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: inhalation

Type of information:

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

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 452 (Chronic Toxicity Studies)

GLP compliance:

not specified

Limit test:

no

Species:

other: rats, hamsters, guinea pigs

Strain:

not specified

Sex:

male/female

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

Aluminium oxide dust was used as a negative control. Two chambers, containing 30 rats and 30 hamsters each, were held at dust concentrations of 100 mg/m3of the pyro powder and the atomized metal powder respectively, two additional chambers were held 50 mg/m3of the respective powders. Six chambers, each containing 30 rats and 15 guinea pigs, were maintained at dust concentrations of 15 and 30 mg/m3respectively, for each of the three types of metallic aluminium powders. The animals were exposed for 6 hr daily, 5 days each week, for 6 months for the 50 and 100 mg/m3groups, and for 12 months for all other animals. An additional group of 30 rats and 30 hamsters was exposed to aluminium oxide dust at an average concentration of 75 mg/m3 for 6 months, and 30 rats and 12 guinea pigs were exposed to aluminium oxide at a concentration of 30 mg/m3 for one year.
Intratracheal injection of the aluminium powders at different dose levels was also conducted.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

6 months; some animals were exposed for 1 year.

Frequency of treatment:

Animals were exposed for 6 hr/day, 5 days/week, for 6
months; some animals were exposed for 1 year.

Remarks:

Doses / Concentrations:
15, 30, 50 , 75 , 100 mg/m3,
Basis:
nominal conc.

No. of animals per sex per dose:

Two chambers, containing 30 rats and 30 hamsters each, Six chambers, each containing 30 rats and 15 guinea pigs, group of 30 rats and 30 hamsters , and group of 30 rats and 12 guinea pigs .

Control animals:

yes

Details on study design:

Rats, guinea pigs, and hamsters were exposed to 3 different types of aluminium powder (British pyro powderflake like particles, American powder with flake like particles, and powder comprised of atomized spherical particles) in inhalation chambers at varying concentrations.
Animals were exposed for 6 hr/day, 5 days/week, for 6 months; some animals were exposed for 1 year

Observations and examinations performed and frequency:

Histological examination of the lungs
All three species of animals developed alveolar proteinosis, the severity and extent of which were not consistently or clearly related either to the type of aluminium powder or to the severity of the dust exposure. The alveolar proteinosis resolved spontaneously and the accumulated dust deposits cleared rapidly from the lungs after cessation of exposure. Intratracheal injection of large doses of aluminium powders into rats produced focal pulmonary fibrosis; no fibrosis occurred in the lungs of hamsters following intratracheal injection.

Clinical signs:

no effects observed

Mortality:

no mortality observed

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:

effects observed, treatment-related

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:

no effects observed

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:

Pulmonary fibrosis was not apparent following inhalation of the aluminium powders in hamsters and guinea pigs; however scattered small scars resulted from foci of lipid pneumonitis in rats.
All three species of animals developed alveolar proteinosis, the severity and extent of which were not consistently or clearly related either to the type of aluminium powder or to the severity of the dust exposure. The alveolar proteinosis resolved spontaneously and the accumulated dust deposits cleared rapidly from the lungs after cessation of exposure. Intratracheal injection of large doses of aluminium powders into rats produced focal pulmonary fibrosis; no fibrosis occurred in the lungs of hamsters following intratracheal injection.

Dose descriptor:

NOAEC

Effect level:

15 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Dose descriptor:

NOAEC

Effect level:

30 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Dose descriptor:

NOAEC

Effect level:

50 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Dose descriptor:

NOAEC

Effect level:

75 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: overall effects Pulmonary fibrosis was not apparent following inhalation of the aluminium powders in hamsters and guinea pigs; however scattered small scars resulted from foci of lipid pneumonitis in rats.

Dose descriptor:

NOAEC

Effect level:

100 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: overall effects Pulmonary fibrosis was not apparent following inhalation of the aluminium powders in hamsters and guinea pigs; however scattered small scars resulted from foci of lipid pneumonitis in rats.

Critical effects observed:

not specified

Conclusions:

The results of this experiment indicate that inhalation of fine metallic aluminium powders does not produce fibrogenic effects, and that intratracheal injection of these powders is likely an artefact of the injection itself.

Executive summary:

The fibrogenic potential of very fine metallic aluminium powder was investigated byGross et al. (1973). Three different types of aluminium powder were tested. Pyro powder and flaked powder were composed of flake-like particles, and the atomized powder consisted of atomized spherical particles.

Aluminium oxide dust was used as a negative control. Two chambers, containing 30 rats and 30 hamsters each, were held at dust concentrations of 100 mg/m³of the pyro powder and the atomized metal powder respectively, two additional chambers were held 50 mg/m³of the respective powders. Six chambers, each containing 30 rats and 15 guinea pigs, were maintained at dust concentrations of 15 and 30 mg/m³respectively, for each of the three types of metallic aluminium powders. The animals were exposed for 6 hr daily, 5 days each week, for 6 months for the 50 and 100 mg/m³groups, and for 12 months for all other animals. An additional group of 30 rats and 30 hamsters was exposed to aluminium oxide dust at an average concentration of 75 mg/m³for 6 months, and 30 rats and 12 guinea pigs were exposed to aluminium oxide at a concentration of 30 mg/m³for one year.

Intratracheal injection of the aluminium powders at different dose levels was also conducted.

 

Pulmonary fibrosis was not apparent following inhalation of the aluminium powders in hamsters and guinea pigs; however scattered small scars resulted from foci of lipid pneumonitis in rats.

All three species of animals developed alveolar proteinosis, the severity and extent of which were not consistently or clearly related either to the type of aluminium powder or to the severity of the dust exposure. The alveolar proteinosis resolved spontaneously and the accumulated dust deposits cleared rapidly from the lungs after cessation of exposure. Intratracheal injection of large doses of aluminium powders into rats produced focal pulmonary fibrosis; no fibrosis occurred in the lungs of hamsters following intratracheal injection.

The results of this experiment indicate that inhalation of fine metallic aluminium powders does not produce fibrogenic effects, and that intratracheal injection of these powders is likely an artefact of the injection itself.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

15 mg/m³

Study duration:

chronic

Species:

rat

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: inhalation

Type of information:

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

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 452 (Chronic Toxicity Studies)

GLP compliance:

not specified

Limit test:

no

Species:

other: rats, hamsters, guinea pigs

Strain:

not specified

Sex:

male/female

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

Aluminium oxide dust was used as a negative control. Two chambers, containing 30 rats and 30 hamsters each, were held at dust concentrations of 100 mg/m3of the pyro powder and the atomized metal powder respectively, two additional chambers were held 50 mg/m3of the respective powders. Six chambers, each containing 30 rats and 15 guinea pigs, were maintained at dust concentrations of 15 and 30 mg/m3respectively, for each of the three types of metallic aluminium powders. The animals were exposed for 6 hr daily, 5 days each week, for 6 months for the 50 and 100 mg/m3groups, and for 12 months for all other animals. An additional group of 30 rats and 30 hamsters was exposed to aluminium oxide dust at an average concentration of 75 mg/m3 for 6 months, and 30 rats and 12 guinea pigs were exposed to aluminium oxide at a concentration of 30 mg/m3 for one year.
Intratracheal injection of the aluminium powders at different dose levels was also conducted.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

6 months; some animals were exposed for 1 year.

Frequency of treatment:

Animals were exposed for 6 hr/day, 5 days/week, for 6
months; some animals were exposed for 1 year.

Remarks:

Doses / Concentrations:
15, 30, 50 , 75 , 100 mg/m3,
Basis:
nominal conc.

No. of animals per sex per dose:

Two chambers, containing 30 rats and 30 hamsters each, Six chambers, each containing 30 rats and 15 guinea pigs, group of 30 rats and 30 hamsters , and group of 30 rats and 12 guinea pigs .

Control animals:

yes

Details on study design:

Rats, guinea pigs, and hamsters were exposed to 3 different types of aluminium powder (British pyro powderflake like particles, American powder with flake like particles, and powder comprised of atomized spherical particles) in inhalation chambers at varying concentrations.
Animals were exposed for 6 hr/day, 5 days/week, for 6 months; some animals were exposed for 1 year

Observations and examinations performed and frequency:

Histological examination of the lungs
All three species of animals developed alveolar proteinosis, the severity and extent of which were not consistently or clearly related either to the type of aluminium powder or to the severity of the dust exposure. The alveolar proteinosis resolved spontaneously and the accumulated dust deposits cleared rapidly from the lungs after cessation of exposure. Intratracheal injection of large doses of aluminium powders into rats produced focal pulmonary fibrosis; no fibrosis occurred in the lungs of hamsters following intratracheal injection.

Clinical signs:

no effects observed

Mortality:

no mortality observed

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:

effects observed, treatment-related

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:

no effects observed

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:

Pulmonary fibrosis was not apparent following inhalation of the aluminium powders in hamsters and guinea pigs; however scattered small scars resulted from foci of lipid pneumonitis in rats.
All three species of animals developed alveolar proteinosis, the severity and extent of which were not consistently or clearly related either to the type of aluminium powder or to the severity of the dust exposure. The alveolar proteinosis resolved spontaneously and the accumulated dust deposits cleared rapidly from the lungs after cessation of exposure. Intratracheal injection of large doses of aluminium powders into rats produced focal pulmonary fibrosis; no fibrosis occurred in the lungs of hamsters following intratracheal injection.

Dose descriptor:

NOAEC

Effect level:

15 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Dose descriptor:

NOAEC

Effect level:

30 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Dose descriptor:

NOAEC

Effect level:

50 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Dose descriptor:

NOAEC

Effect level:

75 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: overall effects Pulmonary fibrosis was not apparent following inhalation of the aluminium powders in hamsters and guinea pigs; however scattered small scars resulted from foci of lipid pneumonitis in rats.

Dose descriptor:

NOAEC

Effect level:

100 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: overall effects Pulmonary fibrosis was not apparent following inhalation of the aluminium powders in hamsters and guinea pigs; however scattered small scars resulted from foci of lipid pneumonitis in rats.

Critical effects observed:

not specified

Conclusions:

The results of this experiment indicate that inhalation of fine metallic aluminium powders does not produce fibrogenic effects, and that intratracheal injection of these powders is likely an artefact of the injection itself.

Executive summary:

The fibrogenic potential of very fine metallic aluminium powder was investigated byGross et al. (1973). Three different types of aluminium powder were tested. Pyro powder and flaked powder were composed of flake-like particles, and the atomized powder consisted of atomized spherical particles.

Aluminium oxide dust was used as a negative control. Two chambers, containing 30 rats and 30 hamsters each, were held at dust concentrations of 100 mg/m³of the pyro powder and the atomized metal powder respectively, two additional chambers were held 50 mg/m³of the respective powders. Six chambers, each containing 30 rats and 15 guinea pigs, were maintained at dust concentrations of 15 and 30 mg/m³respectively, for each of the three types of metallic aluminium powders. The animals were exposed for 6 hr daily, 5 days each week, for 6 months for the 50 and 100 mg/m³groups, and for 12 months for all other animals. An additional group of 30 rats and 30 hamsters was exposed to aluminium oxide dust at an average concentration of 75 mg/m³for 6 months, and 30 rats and 12 guinea pigs were exposed to aluminium oxide at a concentration of 30 mg/m³for one year.

Intratracheal injection of the aluminium powders at different dose levels was also conducted.

 

Pulmonary fibrosis was not apparent following inhalation of the aluminium powders in hamsters and guinea pigs; however scattered small scars resulted from foci of lipid pneumonitis in rats.

All three species of animals developed alveolar proteinosis, the severity and extent of which were not consistently or clearly related either to the type of aluminium powder or to the severity of the dust exposure. The alveolar proteinosis resolved spontaneously and the accumulated dust deposits cleared rapidly from the lungs after cessation of exposure. Intratracheal injection of large doses of aluminium powders into rats produced focal pulmonary fibrosis; no fibrosis occurred in the lungs of hamsters following intratracheal injection.

The results of this experiment indicate that inhalation of fine metallic aluminium powders does not produce fibrogenic effects, and that intratracheal injection of these powders is likely an artefact of the injection itself.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

15 mg/m³

Study duration:

chronic

Species:

rat

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

other:

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

8.55 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

other:

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

4.41 mg/cm²

Study duration:

subacute

Species:

rabbit

Additional information

Dermal exposure:

No studies were located regarding long term exposure local effects in animals after dermal exposure to various forms of Aluminium.

For dermal exposure we taken that:

-the average weight of rats is 250g (200-300g),

-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg

corrected dermal NOAEL= oral NOAEL

342 mg/kg bw/day 0.025 kg =

NOAELrat 8.55 mg/kg bw/day

 

No studies were located regarding long term exposure systemic effects in animals after dermal exposure to various forms of Aluminium.

For dermal exposure we taken that:

-the average weight of rats is 250g (200-300g),

-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg

corrected dermal NOAEL= oral NOAEL

342 mg/kg bw/day 0.025 kg =

NOAELrat 8.55 mg/kg bw/day

 

 

The dose descriptor for dermal irritation/corrosion come from dermal acute study and dermal Repeated toxicity study. In these studies, the dose is reported in the unit mg/kg of body weight/day. This needs to be modified to enable comparison with the human exposure, generally expressed in mg/cm2/day.

 

We have taken that:

• the average weight of rabbits is 2.4 kg , used by LANSDOWN A.B.G..,1973

• the dose is applied over an area which is approximately 10% of the total body surface, and

• the total body surface of rabbits is on the average 1270 cm2 used by LANSDOWN A.B.G.,1973

 

The generic modification from the NOAELtest (in mg/kg of body weight) to NOAELmodified (in mg/cm2/day) will be

NOAELin mg/cm2 =       ((dose in mg/kg bw)x (average animal weight in kg)) / Treated surface in cm2)

 

NOAELtest* 2.4/127= NOAELmodified

 

The highest dose not causing irritation/corrosion was 233.5 mg/kg bw in 5day dermal toxicity study in rabbits of LANSDOWN A.B.G..,1973,

 the modified dose descriptor would be

NOAELmodified =233.5 mg/kg*2.4 kg/127cm2=4.41 mg/cm2

 

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
No studies were located regarding long term exposure local effects in animals after dermal exposure to various forms of Aluminium.
For dermal exposure we taken that:
-the average weight of rats is 250g (200-300g),
-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg
corrected dermal NOAEL= oral NOAEL
342 mg/kg bw/day 0.025 kg =
NOAELrat 8.55 mg/kg bw/day

No studies were located regarding long term exposure systemic effects in animals after dermal exposure to various forms of Aluminium.
For dermal exposure we taken that:
-the average weight of rats is 250g (200-300g),
-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg
corrected dermal NOAEL= oral NOAEL
342 mg/kg bw/day 0.025 kg =
NOAELrat 8.55 mg/kg bw/day

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
The dose descriptor for dermal local effects come from dermal acute study and dermal Repeated toxicity study. In these studies, the dose is reported in the unit mg/kg of body weight/day. This needs to be modified to enable comparison with the human exposure, generally expressed in mg/cm2/day.

We have taken that:
• the average weight of rabbits is 2.4 kg , used by LANSDOWN A.B.G..,1973
• the dose is applied over an area which is approximately 10% of the total body surface, and
• the total body surface of rabbits is on the average 1270 cm2 used by LANSDOWN A.B.G.,1973


The generic modification from the NOAELtest (in mg/kg of body weight) to NOAELmodified (in mg/cm2/day) will be
NOAELin mg/cm2 = ((dose in mg/kg bw)x (average animal weight in kg)) / Treated surface in cm2)

NOAELtest* 2.4/127= NOAELmodified

The highest dose not causing irritation/corrosion was 233.5 mg/kg bw in 5day dermal toxicity study in rabbits of LANSDOWN A.B.G..,1973,
the modified dose descriptor would be
NOAELmodified =233.5 mg/kg*2.4 kg/127cm2=4.41 mg/cm2

Repeated dose toxicity: via oral route - systemic effects (target organ) neurologic: behaviour; neurologic: brain (multiple sections); other: all gross lesions and masses

Repeated dose toxicity: inhalation - systemic effects (target organ) cardiovascular / hematological: lymph nodes; respiratory: lung

Repeated dose toxicity: dermal - systemic effects (target organ) digestive: liver; digestive: stomach; neurologic: behaviour; neurologic: brain (multiple sections); urogenital: kidneys

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

Repeated dose toxicity R33 Danger of cumulative effects. T; R48/23 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation. T; R48/23/24  Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation and in contact with skin. T; R48/23/24/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed. T; R48/23/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed. T; R48/24  Toxic; Toxic: danger of serious damage to health by prolonged exposure in contact with skin. T; R48/24/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure in contact with skin and if swallowed. T; R48/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure if swallowed. Xn; R48/20 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation. Xn; R48/20/21 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation and in contact with skin. Xn; R48/20/21/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed. Xn; R48/20/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation and if swallowed. Xn; R48/21 Harmful; Harmful: danger of serious damage to health by prolonged exposure in contact with skin. Xn; R48/21/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure in contact with skin and if swallowed. Xn; R48/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure if swallowed.

CLP

Repeated dose toxicity STOT Rep. Exp. 1 STOT Rep. Exp. 2 H372: Causes damage to organs <or state all organs affected, if known> through prolonged or repeated exposure <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>. H373: May cause damage to organs <or state all organs affected, if known> through prolonged or repeated exposure <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

 

It is concluded that the substance aluminium sulphate does not meet the criteria to be classified for human health hazards for Repeated dose toxicity