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Description of key information

No repeated dose oral toxicity data is available for the target substance.

In the absence of substance specific data for Alferrock, a conservative approach to hazard evaluation is to assume that aluminium released from Alferrock shows the same systemic hazards as other aluminium compounds with similar or higher bioavailability. Read-across to aluminium compounds with a high release of aluminium ions (soluble Al salts) is considered to represent a worst-case approach that overestimates toxicological properties of the target compound. For details and justification of read-across please refer to the report attached in section 13 of IUCLID.

 

Therefore suitable data available from the read across partner aluminium potassium sulfate were used in the assessment. A subchronic repeated dose oral toxicity study in rats (similar to EU method B.26) and a chronic oral toxicity study in mice (similar to EU method B.33) were conducted using aluminium potassium sulfate. No adverse effects have been reported up to 100,000 ppm in the diet (15,000 mg/kg bw/day).

 

Key value for chemical safety assessment

Toxic effect type:
concentration-driven

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
sub-chronic toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
For details and justification of read-across please refer to the report attached in section 13 of IUCLID.
Reason / purpose for cross-reference:
read-across source
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
A slight body weight gain decrease was observed for the male rats in the 3% A dose group
Food consumption and compound intake (if feeding study):
no effects observed
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
Description (incidence and severity):
Serum levels of phospholipids, triglycerides and total cholesterol in male rats and TG in female rats fed 3% C, 3% A or 3% AC were significantly decreased at the 13th week
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
Serum levels of phospholipids, trigylcerides and total chlosterol in male rats and triglycerides in female rats were decreased in comparison to the control after treatment with 3% aluminium potassium sulfate dodecahydrate
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Dose descriptor:
NOAEL
Effect level:
30 000 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no adverse effects reported at maximum daily dose
Critical effects observed:
not specified
Conclusions:
In this 13-week oral toxicity study treament with 3% (w/w) aluminium potassium sulfate dodecahydrate in the diet led to a decrease in body weight gain after 13 weeks in male rats and to a change of certain clinical chemistry marker in male and female rats. As no effects were seen for clinical signs of toxicity, mortality, histopathologic lesions, haematology or organ weights the NOAEL can be considered to be 30.000 ppm.
Executive summary:

In a 13-weeks subchronic oral toxicity study (similar to EU method B.26) aluminium potassium sulfate dodecahydrate was administered orally via the diet to 15 male and female Wistar rats up to a concentration of 30000 ppm (3% w/w). The animals were treated with the test item 7 days per week for a period of 13 weeks, whereas 7 animals/sex/group were sacrificed after 4 weeks. The treatment led to a decrease in body weight gain after 13 weeks in male Wistar rats. Additionally, serum levels of phospholipids, trigylcerides and total chlosterol in male rats and triglycerides in female rats were decreased in comparison to the control after treatment with 3% aluminium potassium sulfate dodecahydrate. As no effects were seen for clinical signs of toxicity, mortality, histopathologic lesions, haematology or organ weights the NOAEL can be considered to be 30.000 ppm.

This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the attached read-across report (see IUCLID section 13).

Endpoint:
chronic toxicity: oral
Remarks:
combined repeated dose and carcinogenicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
For details and justification of read-across please refer to the report attached in section 13 of IUCLID.
Reason / purpose for cross-reference:
read-across source
Clinical signs:
no effects observed
Mortality:
no mortality observed
Description (incidence):
The survival rates at the end of the dosing period were 73.3% (male) and 78.3% (female) in the control group, and 86.7%-95.0% (male) and 86.7-91.7% (female) in the treatment group.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Both the male and the female mice in the high dose level exhibited slight growth retardation compared with the control group after 1 month, and those in the 1.0 and 2.5 % dose groups exhibited a slight increase in body weight after 3 months. Both male and female mice receiving 5.0% test item showed growth similar to that in the control group.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
Food consumption did not show any variation among the groups throughout the experimental period for either males or females.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
A significant increase in the absolute organ weight was observed in the kidneys and heart in both sexes in the 1.0, 2.5 and 5.0% dose groups, in the pituitary in the males in the 2.5% dose group and the brain in the females in the 1.0% group compared with those in the control group. Additionally, there were significant decreases in the absolute organ weight of the liver in both sexes in the 5.0 and 10.0% dose groups, the heart and brain in both sexes in the high dose group and lungs in the males and spleen in the females in the 10% high dose group compared with those in the control group. There was a significant increase in the relative organ weight of the kidneys in the males in the 5.0% dose group and a significant decrease in the relative organ weight of the liver in both sexes in 5.0 and 10% groups and spleen in the females in the high dose group.
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
The incidence of myocardial eosinophilic cytoplasm showed a significant dose-dependent decrease in the male mice in the treatment groups. A comparison between the sexes revealed a significant decrease in the incidence of hepatocytic anisonucleosis, myocardial eosinophilic cytoplasm and acinar cell vacuolation of sumandibular gland in females; and lymphocyte infiltration in the renal cortex and pelvis, and vacuolation of cerebrellar white matter in the males
Histopathological findings: neoplastic:
no effects observed
Description (incidence and severity):
The incidence of the male tumour bearing mice was 40.9%, and 54.5, 36.5, 42.9 and 17.5% in the control group and 1.0, 2.5, 5.0 and 10.0% dose groups, respectively, while that of female tumour.bearing mice was 29.8, 23.6, 17.3, 11.5 and 13.5% respectively.

HISTORICAL DATA
The incidence of all tumours and non-tumorous changes was within the normal range reported for spontaneous changes in B6C3F1 mice.
Dose descriptor:
NOAEL
Effect level:
100 000 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effects notified
Critical effects observed:
no
Conclusions:
In conclusion, the results of the present study indicate that long-term administration of a diet containing 10% (w/w) aluminium potassium sulfate does not exert tumorgenicity or any other toxic actions in male and female B6C3F1 mice. Thus, the NOAEL can be considered to be 100000 ppm (10 % w/w).
Executive summary:

In a chronic (20 months) combined repeated oral dose toxicity and carcinogenicity study (similar to EU method B.33) aluminium potassium sulfate dodecahydrate was administered orally via the diet to 60 male and female B6C3F1 mice at concentrations of 0, 10000, 25000, 50000 and 100000 ppm. The animals were treated with the test item 7 days per week for a period of 20 months. The treatment does not exert tumourgenicity or any other toxic action (mortality, food consumption, body weights, organ weights and histopathology) in any dose group investigated. Based on the results the chronic NOAEL for both sexes can be considered to be 100000 ppm which equals 15000 mg/kg bw/day.

This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the attached read-across report (see IUCLID section 13).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
15 000 mg/kg bw/day
Study duration:
chronic
Species:
mouse
Quality of whole database:
Well documented chronic toxicity study with aluminium potassium sulfate (AlK(SO4)2*12H2O) used as read-across partner

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

For human health endpoints, the relative bioavailability of different metal-ions from ALFERROCK would determine its potential to cause toxicological effects and also govern the severity of such effects. According to the results of the bioelution testing,aluminium has the highest relative release into artificial physiological media representing relevant exposure routes and therefore was considered as main constituent for the human health hazard/risk assessment of Alferrock (Klawonn, 2021, please see IUCLID section 7.1.1).

No repeated dose oral toxicity data is available for the test substance. However, suitable data is available from the read across partner aluminium potassium sulfate. Due to higher water solubility of aluminium potassium sulfate compared to the aluminium release from test substance, the resulting bioavailability of aluminium from the test substance would also be expected to be lower. Therefore, the read-across to the source substance aluminium potassium sulfate is adequately protective. Details on the read-across rationale are provided in section 13.

A subchronic repeated dose oral toxicity study in rats (similar to EU method B.26) and a chronic oral toxicity study in mice (similar to EU method B.33) were conducted using aluminium potassium sulfate. As no effects were seen for clinical signs of toxicity, mortality, histopathologic lesions, haematology or organ weights in the subchronic study, the NOAEL can be considered to be 30,000 ppm. The results of the chronic toxicity study indicate that long-term administration (20 months) of a diet containing 0, 1.0, 2.5, 5.0 and 10.0% aluminium potassium sulfate (AlK(SO4)2*12H2O) does not exert tumorigenicity or any other toxic action (mortality, food consumption, body weights, organ weights and histopathology) in sixty B6C3F1 mice of each sex/dose. Therefore, the chronic NOAEL for both sexes can be considered to be 100,000 ppm in the diet which equals 15,000 mg/kg bw/day (by applying a default conversion factor of 0.15 as recommended in an EFSA guidance document).


Justification for classification or non-classification

Based on the results of (sub-)chronic repeated dose toxicity studies with a read-across analogue substance, classification of the target substance according to the criteria set out in Annex I of Regulation (EC) 1272/2008 (CLP Regulation) is not warranted.