Aluminium sulphate

Immunotoxicity

Description of key information

Orale exposure:
After three months treatment with Al2(SO4)3 in a dose of 300 mg/kg bw., hemoglobin and hematocrit levels of Al and Al+Vit E groups were significantly decreased compared to the control. Reductions in serum haemoglobin (14%) and haematocrit (13%) were described. There was an increase in the levels of liver iron (59%) and ferritin with Al, but Vit E had no effect on the changes of all blood and liver parameters caused by Al. From the results presented in this report, a Lowest Observed Adverse Effect Level (LOAEL) for Aluminium sulfate of 300 mg/kg/day was established, based on significantly decreased hemoglobin and hematocrit levels of Al .
Inhalation exposure:
Several animal studies have found histological alterations in the lymphoreticular system, in particular granulomas in the hilar lymph nodes; these effects are secondary to the pulmonary effects (Steinhagen et al. 1978; Thomson et al. 1986) and resulted from the removal of aluminum from the lungs by alveolar macrophages.
Dermal exposure:
No studies were located regarding immunological/lymphoreticular effects in animals after dermal exposure to various forms of aluminum.
For dermal exposure we taken that: 
-the average weight of mouse is 80g (60-100g), 
-the dose is applied over an area which is approximately 10% of the total body surface=0.008kg 
corrected dermal LOAEL= oral LOAEL 
300 mg/kg bw/dw 0.008 kg = 
LOAELmouse 2.4 mg/kg bw/day 

Key value for chemical safety assessment

Effect on immunotoxicity: via oral route

Link to relevant study records

Reference

Endpoint:

immunotoxicity

Remarks:

chronic

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:

equivalent or similar to guideline

Guideline:

EPA OPP 85-7 (Immunotoxicity)

Deviations:

yes

GLP compliance:

not specified

Limit test:

no

Species:

mouse

Strain:

Balb/c

Sex:

female

Details on test animals or test system and environmental conditions:

This study was performed on 21 adult female Balb-c mice that were aged 16 to 20 weeks. The animals were divided into three groups (n=7 each). All rats were fed ad libitum.

Route of administration:

other: Ad libitum

Vehicle:

unchanged (no vehicle)

Details on exposure:

This study was performed on 21 adult female Balb-c mice that were aged 16 to 20 weeks. The animals were divided into three groups (n=7 each). All rats were fed ad libitum. In the first and second groups, 877/µmol Al2(SO4)3 (aluminum sulfate)/kg body weight were daily given in the drinking water for three months. Vitamin E (Vit E; a -tocopherol) was also administered once a week (20 mg/kg body weight) by subcutaneous injection in to the animals of the second group during the three months. The animals of the con¬trol group were given only drinking water during this period. At the end of the experimental period, all the animals were anaesthetized with ether vapor, and blood was removed by cardiac punc¬ture, after which the animals were killed by cervical dislocation.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

three months

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:
877 μmol/kg b.w./day = 300 mg /kg b.w./day aluminium sulphate
Basis:
nominal in water

No. of animals per sex per dose:

21 adult female Balb-c mice

Control animals:

yes

Details on study design:

See attached material

Observations and clinical examinations performed and frequency:

This study was performed on 21 adult female Balb-c mice that were aged 16 to 20 weeks. The animals were divided into three groups (n=7 each). All rats were fed ad libitum. In the first and second groups, 877/µmol Al2(SO4)3 (aluminum sulfate)/kg body weight were daily given in the drinking water for three months. Vitamin E (Vit E; a -tocopherol) was also administered once a week (20 mg/kg body weight) by subcutaneous injection in to the animals of the second group during the three months.
The animals of the control group were given only drinking water during this period. At the end of the experimental period, all the animals were anaesthetized with ether vapor, and blood was removed by cardiac punc¬ture, after which the animals were killed by cervical dislocation. Whole blood samples and sera of the subjects were collected into tubes. Hemoglobin concentrations and hematocrit levels were determined in the whole blood, while the levels of ferritin, transferrin, iron, and total iron binding capacity (TIBC) were determined in the serum.
The liver tissue samples were taken immediately after the sacrifices, weighed, and diluted with distillate water in the ratio of 1:1. Then, the samples were homogenated. The homogenates were centrifuged at 2000 x g for 6 minutes, and supernatants were obtained. Iron levels of the supernatants and sera were analyzed with commercial kits (ILAB, Milano, Italy) by using an auto analyzer (ILAB 900, Milano, Italy). Ferritin levels of the supernatants and sera were determined by an immune-analyzer (Tosoh Corporation, Tokyo, Japan) with commercial kits (Eurogenetics, Tessenderlo, Belgium). Serum transferrin and TIBC levels were analyzed with commercial kits (ILAB, Milano, Italy) by using an auto analyzer (ILAB 900, Milano, Italy). The percentage of transferrin saturation of blood samples was calculated.

The results were evaluated with Mann Whitney U and Kruskal Wallis tests for the significance
between and among groups, respectively. Statisti¬cal analysis was made with SPSS 9.0 (Statistical Package for Social Sciences). The results are expressed as a mean ± standard deviation (S.D.). Animal care and all experimental procedures used were in accordance with those detailed in the Guide for Care and Use of Laboratory Ani¬mals, which was published by the U.S. Depart¬ment of Health and Human Services.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Cell viabilities:

See attached material

Humoral immunity examinations:

See attached material

Specific cell-mediated immunity:

See attached material

Non-specific cell-mediated immunity:

See attached material

Other examinations:

See attached material

Statistics:

See attached material

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

hemoglobin and hematocrit levels of Al and Al+Vit E groups were significantly decreased compared to the control. Reductions in serum haemoglobin (14%) and haematocrit (13%) were described. There was an increase in the levels of liver iron (59%) and ferri

Mortality:

mortality observed, treatment-related

Description (incidence):

hemoglobin and hematocrit levels of Al and Al+Vit E groups were significantly decreased compared to the control. Reductions in serum haemoglobin (14%) and haematocrit (13%) were described. There was an increase in the levels of liver iron (59%) and ferri

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):

effects observed, treatment-related

Ophthalmological findings:

effects observed, treatment-related

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

hemoglobin and hematocrit levels of Al and Al+Vit E groups were significantly decreased compared to the control. Reductions in serum haemoglobin (14%) and haematocrit (13%) were described. There was an increase in the levels of liver iron (59%) and ferri

Urinalysis findings:

effects observed, treatment-related

Gross pathological findings:

no effects observed

Details on results:

The data and statistical comparisons of blood parameters for the group with chronically admin¬istered Al (Al group), the group with chronically administered Al plus Vit E (Al+Vit E group), and the control group are illustrated in Table 1. Hemoglobin and hematocrit levels of Al and Al+Vit E groups were significantly decreased compared to the control.
Table 2 shows the data and statistical compari¬sons of liver tissue parameters for the Al group, the Al+Vit E group, and the control group. Iron and ferritin levels of the two groups were significantly higher than those of the control.
When the Al group and the Al+Vit E group were compared, we found no significant differ¬ences in the levels of all blood and tissue parame¬ters (Table 1, Table 2).

Cell viabilities:

effects observed, treatment-related

Humoral immunity examinations:

effects observed, treatment-related

Specific cell-mediated immunity:

effects observed, treatment-related

Non-specific cell-mediated immunity:

effects observed, treatment-related

Other functional activity assays:

effects observed, treatment-related

Other findings:

effects observed, treatment-related

Dose descriptor:

LOAEL

Effect level:

300 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: see 'Remark'

Table 1.Blood Parameters of Aluminum, Aluminum+Vitamin E and Control Groups (Mean ± S.D.)

	Control (n=7)	Aluminum (n=7)	Aluminum+Vitamin E (n=7)
Hemoglobin (g/dl)	15.32 ± 0.24^a*,^b*,^c*	13.18 ± 1.60^a*,^c*	13.68± 1.16^b*,^c*
Hematocrit (%)	35.20 ± 1.74^a*,^b*,^c*	30.75 ± 2.68^a*,^c*	31..34± 2.73^b*,^c*
Transferrin (mg/dl)	132.85 ± 4.59	143.14 ± 18.39	140..85± 26.92
Iron (mg/dl)	42.00± 41.13	67.42± 56.68	96.85 ± 82.75
TIBC(µg/dl)	601.00 ±26.94	620.71 ± 41.12	636.00 ± 65.17
Ferritin (ng/ml)	0.08±0.02	0.06 ± 0.03	0.08± 0.06
Transferrin saturation (%)	6.75±6.24	10.43    ± 8.00	14.31± 10.71

 

a and b: Shows significance between two groups.

c: Shows significance among three groups. TIBC: Total iron binding capacity.

*p<0.05.

Table 2.Liver Parameters of Aluminum, Aluminum+Vitamin E and Control Groups (Mean ± S.D.)

	Control (n=7)	Aluminum (n=7)	Aluminum+Vitamin E (n=7)
Iron (µg/dl)	2.02 ± 0.33^a*,^b*	2.64 ± 0.47^a*	2.59 ± 0.55^b*
Ferritin (ng/ml)	2.16 ± 0.90^a+,^b+,^c+	4.69 ± 1.69^a+,^c+	4.40 ± 1.1^b+,^c+

a and b: Shows significance between two groups. c: Shows significance among three groups.

TIBC: Total iron binding capacity.

*p<0.05,⁺p<0.01

Conclusions:

Turgut et al. (2004)exposed mice to aluminium for 3 months through drinking water containing aluminium sulphate. The estimated dose was 877 μmol/kg b.w./day = 300 mg of /kg b.w./day. Serum levels of aluminium were not reported. Reductions in serum haemoglobin (14%) and haematocrit (13%) were described. The levels of iron in serum were elevated by 59% with a small increase in the levels of Tf.

Executive summary:

After three months treatment with Al2(SO4)3 in a dose of 300 mg/kg bw., hemoglobin and hematocrit levels of Al and Al+Vit E groups were significantly decreased compared to the control. Reductions in serum haemoglobin (14%) and haematocrit (13%) were described. There was an increase in the levels of liver iron (59%) and ferritin with Al, but Vit E had no effect on the changes of all blood and liver parameters caused by Al. From the results presented in this report, a Lowest Observed Adverse Effect Level (LOAEL) for Aluminium sulfate of 300 mg/kg/day was established, based on significantly decreased hemoglobin and hematocrit levels of Al .

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LOAEL

300 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Effect on immunotoxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

immunotoxicity: chronic inhalation

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.

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPP 85-7 (Immunotoxicity)

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

adults Fischer 344 rats and Hartley guinea pigs

Route of administration:

inhalation: dust

Vehicle:

other: Wright dust feed mechanism.

Details on exposure:

Groups of rats and guinea pigs were exposed, by inhalation, to 0.25, 2.5, and 25 mg/m3 of aluminum chlorhydrate (ACH) for six months to study the effects of a common component of antiperspirants. Similar groups of animals of both species exposed to clean air served as controls. The ACH was generated as a particulate dust using a Wright dust feed mechanism. After six months of exposure, animals were sacrificed.

Duration of treatment / exposure:

6 months

Frequency of treatment:

5 day/ week, 6 hours/day

Remarks:

Doses / Concentrations:
0.25, 2.5, and 25 mg/m3 of aluminum chlorhydrate (ACH) for six months
Basis:
actual ingested

Control animals:

yes

Observations and clinical examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:daily

BODY WEIGHT: Yes
- Time schedule for examinations:daily


OPHTHALMOSCOPIC EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Decreases in body weight were seen in rats exposed to 25 mgAl/m3 of ACH.

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:

not examined

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

not examined

Gross pathological findings:

no effects observed

Details on results:

NOAEL -3.8 mg/m³ air was estabished. Histological alterations in the lymphoreticular system, in particular granulomas in the hilar lymph nodes; these effects are secondary to the pulmonary effects and resulted from the removal of aluminum from the lungs by alveolar macrophages.

Cell viabilities:

no effects observed

Humoral immunity examinations:

no effects observed

Specific cell-mediated immunity:

no effects observed

Non-specific cell-mediated immunity:

no effects observed

Other functional activity assays:

not examined

Other findings:

not examined

Dose descriptor:

NOAEL

Effect level:

3.8 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Histological alterations in the lymphoreticular system, in particular granulomas in the hilar lymph nodes; these effects are secondary to the pulmonary effects and resulted from the removal of aluminum from the lungs by alveolar macrophages.

Conclusions:

NOAEL -3.8 mg/m³ air was estabished. Histological alterations in the lymphoreticular system, in particular granulomas in the hilar lymph nodes; these effects are secondary to the pulmonary effects and resulted from the removal of aluminum from the lungs by alveolar macrophages.

Executive summary:

Groups of rats and guinea pigs were exposed, by inhalation, to 0.25, 2.5, and 25 mgAl/m3 of aluminum chlorhydrate (ACH) for six months to study the effects of a common component of antiperspirants. Similar groups of animals of both species exposed to clean air served as controls. The ACH was generated as a particulate dust using a Wright dust feed mechanism. After six months of exposure, animals were sacrificed. Decreases in body weight were seen in rats exposed to 25 mg/m3 of ACH. Marked increases in lung weights and significant increases in lung to body weight ratios were seen in rats and guinea pigs exposed to 25 mg/m3 of ACH. The lungs of all rats and guinea pigs showed significant dose-related increases in aluminum accumulation when exposed to either 0.25, 2.5, or 25 mg/m3 of ACH. The lungs of all rats and guinea pigs exposed to either 2.5 or 25 mg/m3 of ACH contained exposure-related granulomatous reactions characterized by giant vacuoled macrophages containing basophilic material in association with eosinophilic cellular debris.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

3.8 mg/m³

Study duration:

chronic

Species:

rat

Effect on immunotoxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

immunotoxicity

Remarks:

chronic

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:

equivalent or similar to guideline

Guideline:

EPA OPP 85-7 (Immunotoxicity)

Deviations:

yes

GLP compliance:

not specified

Limit test:

no

Species:

mouse

Strain:

Balb/c

Sex:

female

Details on test animals or test system and environmental conditions:

This study was performed on 21 adult female Balb-c mice that were aged 16 to 20 weeks. The animals were divided into three groups (n=7 each). All rats were fed ad libitum.

Route of administration:

other: Ad libitum

Vehicle:

unchanged (no vehicle)

Details on exposure:

This study was performed on 21 adult female Balb-c mice that were aged 16 to 20 weeks. The animals were divided into three groups (n=7 each). All rats were fed ad libitum. In the first and second groups, 877/µmol Al2(SO4)3 (aluminum sulfate)/kg body weight were daily given in the drinking water for three months. Vitamin E (Vit E; a -tocopherol) was also administered once a week (20 mg/kg body weight) by subcutaneous injection in to the animals of the second group during the three months. The animals of the con¬trol group were given only drinking water during this period. At the end of the experimental period, all the animals were anaesthetized with ether vapor, and blood was removed by cardiac punc¬ture, after which the animals were killed by cervical dislocation.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

three months

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:
877 μmol/kg b.w./day = 300 mg /kg b.w./day aluminium sulphate
Basis:
nominal in water

No. of animals per sex per dose:

21 adult female Balb-c mice

Control animals:

yes

Details on study design:

See attached material

Observations and clinical examinations performed and frequency:

This study was performed on 21 adult female Balb-c mice that were aged 16 to 20 weeks. The animals were divided into three groups (n=7 each). All rats were fed ad libitum. In the first and second groups, 877/µmol Al2(SO4)3 (aluminum sulfate)/kg body weight were daily given in the drinking water for three months. Vitamin E (Vit E; a -tocopherol) was also administered once a week (20 mg/kg body weight) by subcutaneous injection in to the animals of the second group during the three months.
The animals of the control group were given only drinking water during this period. At the end of the experimental period, all the animals were anaesthetized with ether vapor, and blood was removed by cardiac punc¬ture, after which the animals were killed by cervical dislocation. Whole blood samples and sera of the subjects were collected into tubes. Hemoglobin concentrations and hematocrit levels were determined in the whole blood, while the levels of ferritin, transferrin, iron, and total iron binding capacity (TIBC) were determined in the serum.
The liver tissue samples were taken immediately after the sacrifices, weighed, and diluted with distillate water in the ratio of 1:1. Then, the samples were homogenated. The homogenates were centrifuged at 2000 x g for 6 minutes, and supernatants were obtained. Iron levels of the supernatants and sera were analyzed with commercial kits (ILAB, Milano, Italy) by using an auto analyzer (ILAB 900, Milano, Italy). Ferritin levels of the supernatants and sera were determined by an immune-analyzer (Tosoh Corporation, Tokyo, Japan) with commercial kits (Eurogenetics, Tessenderlo, Belgium). Serum transferrin and TIBC levels were analyzed with commercial kits (ILAB, Milano, Italy) by using an auto analyzer (ILAB 900, Milano, Italy). The percentage of transferrin saturation of blood samples was calculated.

The results were evaluated with Mann Whitney U and Kruskal Wallis tests for the significance
between and among groups, respectively. Statisti¬cal analysis was made with SPSS 9.0 (Statistical Package for Social Sciences). The results are expressed as a mean ± standard deviation (S.D.). Animal care and all experimental procedures used were in accordance with those detailed in the Guide for Care and Use of Laboratory Ani¬mals, which was published by the U.S. Depart¬ment of Health and Human Services.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Cell viabilities:

See attached material

Humoral immunity examinations:

See attached material

Specific cell-mediated immunity:

See attached material

Non-specific cell-mediated immunity:

See attached material

Other examinations:

See attached material

Statistics:

See attached material

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

hemoglobin and hematocrit levels of Al and Al+Vit E groups were significantly decreased compared to the control. Reductions in serum haemoglobin (14%) and haematocrit (13%) were described. There was an increase in the levels of liver iron (59%) and ferri

Mortality:

mortality observed, treatment-related

Description (incidence):

hemoglobin and hematocrit levels of Al and Al+Vit E groups were significantly decreased compared to the control. Reductions in serum haemoglobin (14%) and haematocrit (13%) were described. There was an increase in the levels of liver iron (59%) and ferri

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):

effects observed, treatment-related

Ophthalmological findings:

effects observed, treatment-related

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

hemoglobin and hematocrit levels of Al and Al+Vit E groups were significantly decreased compared to the control. Reductions in serum haemoglobin (14%) and haematocrit (13%) were described. There was an increase in the levels of liver iron (59%) and ferri

Urinalysis findings:

effects observed, treatment-related

Gross pathological findings:

no effects observed

Details on results:

The data and statistical comparisons of blood parameters for the group with chronically admin¬istered Al (Al group), the group with chronically administered Al plus Vit E (Al+Vit E group), and the control group are illustrated in Table 1. Hemoglobin and hematocrit levels of Al and Al+Vit E groups were significantly decreased compared to the control.
Table 2 shows the data and statistical compari¬sons of liver tissue parameters for the Al group, the Al+Vit E group, and the control group. Iron and ferritin levels of the two groups were significantly higher than those of the control.
When the Al group and the Al+Vit E group were compared, we found no significant differ¬ences in the levels of all blood and tissue parame¬ters (Table 1, Table 2).

Cell viabilities:

effects observed, treatment-related

Humoral immunity examinations:

effects observed, treatment-related

Specific cell-mediated immunity:

effects observed, treatment-related

Non-specific cell-mediated immunity:

effects observed, treatment-related

Other functional activity assays:

effects observed, treatment-related

Other findings:

effects observed, treatment-related

Dose descriptor:

LOAEL

Effect level:

300 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: see 'Remark'

Table 1.Blood Parameters of Aluminum, Aluminum+Vitamin E and Control Groups (Mean ± S.D.)

	Control (n=7)	Aluminum (n=7)	Aluminum+Vitamin E (n=7)
Hemoglobin (g/dl)	15.32 ± 0.24^a*,^b*,^c*	13.18 ± 1.60^a*,^c*	13.68± 1.16^b*,^c*
Hematocrit (%)	35.20 ± 1.74^a*,^b*,^c*	30.75 ± 2.68^a*,^c*	31..34± 2.73^b*,^c*
Transferrin (mg/dl)	132.85 ± 4.59	143.14 ± 18.39	140..85± 26.92
Iron (mg/dl)	42.00± 41.13	67.42± 56.68	96.85 ± 82.75
TIBC(µg/dl)	601.00 ±26.94	620.71 ± 41.12	636.00 ± 65.17
Ferritin (ng/ml)	0.08±0.02	0.06 ± 0.03	0.08± 0.06
Transferrin saturation (%)	6.75±6.24	10.43    ± 8.00	14.31± 10.71

 

a and b: Shows significance between two groups.

c: Shows significance among three groups. TIBC: Total iron binding capacity.

*p<0.05.

Table 2.Liver Parameters of Aluminum, Aluminum+Vitamin E and Control Groups (Mean ± S.D.)

	Control (n=7)	Aluminum (n=7)	Aluminum+Vitamin E (n=7)
Iron (µg/dl)	2.02 ± 0.33^a*,^b*	2.64 ± 0.47^a*	2.59 ± 0.55^b*
Ferritin (ng/ml)	2.16 ± 0.90^a+,^b+,^c+	4.69 ± 1.69^a+,^c+	4.40 ± 1.1^b+,^c+

a and b: Shows significance between two groups. c: Shows significance among three groups.

TIBC: Total iron binding capacity.

*p<0.05,⁺p<0.01

Conclusions:

Turgut et al. (2004)exposed mice to aluminium for 3 months through drinking water containing aluminium sulphate. The estimated dose was 877 μmol/kg b.w./day = 300 mg of /kg b.w./day. Serum levels of aluminium were not reported. Reductions in serum haemoglobin (14%) and haematocrit (13%) were described. The levels of iron in serum were elevated by 59% with a small increase in the levels of Tf.

Executive summary:

After three months treatment with Al2(SO4)3 in a dose of 300 mg/kg bw., hemoglobin and hematocrit levels of Al and Al+Vit E groups were significantly decreased compared to the control. Reductions in serum haemoglobin (14%) and haematocrit (13%) were described. There was an increase in the levels of liver iron (59%) and ferritin with Al, but Vit E had no effect on the changes of all blood and liver parameters caused by Al. From the results presented in this report, a Lowest Observed Adverse Effect Level (LOAEL) for Aluminium sulfate of 300 mg/kg/day was established, based on significantly decreased hemoglobin and hematocrit levels of Al .

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LOAEL

2.4 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Additional information

Orale exposure:

After three months treatment with Al2(SO4)3 in a dose of 300 mg/kg bw., hemoglobin and hematocrit levels of Al and Al+Vit E groups were significantly decreased compared to the control. Reductions in serum haemoglobin (14%) and haematocrit (13%) were described. There was an increase in the levels of liver iron (59%) and ferritin with Al, but Vit E had no effect on the changes of all blood and liver parameters caused by Al. From the results presented in this report, a Lowest Observed Adverse Effect Level (LOAEL) for Aluminium sulfate of 300 mg/kg/day was established, based on significantly decreased hemoglobin and hematocrit levels of Al .

Inhalation exposure:

Several animal studies have found histological alterations in the lymphoreticular system, in particular granulomas in the hilar lymph nodes; these effects are secondary to the pulmonary effects (Steinhagen etal. 1978; Thomson et al. 1986) and resulted from the removal of aluminum from the lungs by alveolar macrophages.

Dermal exposure:

No studies were located regarding immunological/lymphoreticular effects in animals after dermal exposure to various forms of aluminium.

For dermal exposure we taken that:

-the average weight ofmouseis80g (60-100g),

-the dose is applied over an area which is approximately 10% of the total bodysurface=0.008kg

corrected dermal LOAEL= oral LOAEL

300 mg/kg bw/dw 0.008kg =

LOAELmouse2.4mg/kg bw/day

 

Justification for selection of effect on immunotoxicity via dermal route endpoint:
Dermal exposure:
No studies were located regarding immunological/lymphoreticular effects in animals after dermal exposure to various forms of aluminium.
For dermal exposure we taken that:
-the average weight of mouse is 80g (60-100g),
-the dose is applied over an area which is approximately 10% of the total body surface=0.008kg
corrected dermal LOAEL= oral LOAEL
300 mg/kg bw/dw 0.008 kg =
LOAELmouse 2.4 mg/kg bw/day

Justification for classification or non-classification

There are conclusive but not suffcient data for the classification of substance Aluminium sulphate with regard to immunotoxicity.