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Carcinogenicity

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Description of key information

There are conclusive but not suffcient data for the classification of substance Aluminium sulphate with regard to carcinogenicity.
Evidence for Carcinogenicity:
A4: Not classifiable as a human carcinogen. /Aluminum metal and insoluble compounds/
[American Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH, 2008, p. 11]
 

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records
Reference
Endpoint:
carcinogenicity: oral
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:
according to guideline
Guideline:
EPA OPPTS 870.4300 (Combined Chronic Toxicity / Carcinogenicity)
GLP compliance:
not specified
Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals or test system and environmental conditions:
B6C3F1 mice (60 males and 60 females per group)
Route of administration:
oral: feed
Type of inhalation exposure (if applicable):
whole body
Vehicle:
unchanged (no vehicle)
Details on exposure:
Administration of aluminium potassium sulphate (APS) to B6C3F1 mice (60 males and 60 females per group) at levels of 1,2.5, 5 or 10% in the diet for 20 months (equivalent to 1500, 3750, 7500 or 15000 mg/kgbw/day of aluminium potassium sulphate and 85, 213, 427 or 853 mg Al/kg bw/day).One group receiving the basal diet served as the control.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
20 months
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
0, 2.5, 5.0 and 10.0% (w/w).
Basis:
nominal in diet
No. of animals per sex per dose:
B6C3F1 mice (60 males and 60 females per group)
Control animals:
yes
Details on study design:
This study involved the administration of aluminium potassium sulphate (APS) to B6C3F1 mice (60 males and 60 females per group) at levels of 1,2.5, 5 or 10% in the diet for 20 months (equivalent to 1500, 3750, 7500 or 15000 mg/kgbw/day of aluminium potassium sulphate and 85, 213, 427 or 853 mg Al/kg bw/day).
Positive control:
One group receiving the basal diet served as the control.
Observations and examinations performed and frequency:
This study involved the administration of aluminium potassium sulphate (APS) to B6C3F1 mice (60 males and 60 females per group) at levels of 1,2.5, 5 or 10% in the diet for 20 months (equivalent to 1500, 3750, 7500 or 15000 mg/kgbw/day of aluminium potassium sulphate and 85, 213, 427 or 853 mg Al/kg bw/day).
Body weight gain was reduced in the mice receiving 10% APS and increased in the groups receiving1 or 2.5%, while those receiving 5% showed similar weight gains to controls.
Survival rates were marginally increased in all APS-treated mice compared with controls, and there was noevidence of Al-related toxicity in any of the treated groups. There was also no increase in the incidence of gross tumours, neoplastic lesions, or other proliferative lesions in treated micecompared with controls. Animals receiving 10% APS in the diet showed asignificantly lowerincidence in total tumours compared with controls, which was mainly attributable to areduction in the incidence of hepatocellular carcinoma, although incidence of other tumourssuch as pulmonary adenocarcinoma and Harderian gland adenomas were also reduced. The lower tumour incidence was in turn attributed to the reduced body weight gain seen in animalsat this dose level. The authors concluded that there was no evidence of tumourogenicity or anyother toxic actions of APS in B6C3F1 mice in this study
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
In the tumor pathology, the incidence of hepatocellular carcinoma was significantly decreased in the males in the 10% APS treated group.
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
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
Details on results:
This study showed no increase in the incidence of gross tumours, neoplastic lesions, or other proliferative lesions in B6C3F1 mice following dietary exposure to up to 850 mg Al/kg/day for 20-24 months. Interestingly, in all groups, the incidence of spontaneous hepatocellular carcinoma was significantly decreased in the females. This was also significantly decreased in the high-dose group males (5.5 vs. 20.5% in controls) and the incidence of myocardial eosinophilic cytoplasm showed a dose-dependent decrease with aluminium exposure.

Dose descriptor:
NOAEL
Effect level:
850 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: see 'Remark'
Remarks on result:
other: Effect type: carcinogenicity (migrated information)

A more recent study byOneda et al. (1994)showed no increase in the incidence of gross tumours, neoplastic lesions, or other proliferative lesions in B6C3F1mice following dietary exposure to up to 979 mg Al/kg/day for 20-24 months. Interestingly, in all groups, the incidence of spontaneous hepatocellular carcinoma was significantly decreased in the females. This was also significantly decreased in the high-dose group males (5.5 vs. 20.5% in controls) and the incidence of myocardial eosinophilic cytoplasm showed a dose-dependent decrease with aluminium exposure.
Conclusions:
This study for B6C3F1 mouse did not however indicate any carcinogenic potential of aluminium potassium sulphate at levels of up to 850 mg Al/kg bw/day in the diet. The Panel also noted the absence of epidemiological evidence for carcinogenicity of aluminium compounds used therapeutically, and the conclusion of IARC that aluminium itself is unlikely to be a human carcinogen, despite the observation of an association between inhalation exposure to aluminium dust and aluminium compounds during production/processing and cancer in workers.
Executive summary:

The tumorigenic potential of aluminum potassium sulfate [A1K (SO4)2 12H2O, APS], a compound which exists widely in the environment, was investigated in B6C3F1 mice. APS was administered in the diet for 20 months at dose levels of 1.0, 2.5, 5.0 and 10.0% (w/w). One group receiving the basal diet served as the control. Body weight gain in both sexes was decreased in the 10.0% APS treated group, and increased in the 1.0 and 2.5% APS treated groups. 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 APS treated groups. The survival rate showed a tendency to increase in both sexes in all the APS treated groups. In the tumor pathology, the incidence of hepatocellular carcinoma was significantly decreased in the males in the 10% APS treated group. The incidence of hepatocellular carcinoma was significantly decreased in females in all groups including the control group. As regards the nontumorous pathology, the incidence of myocardial eosinophilic cytoplasm showed a significant dose-dependent decrease in males in the APS treated groups. A comparison between the sexes revealed a significant decrease in the incidence of hepatocytic anisonucleosis, myocardial eosinophilic cytoplasm and acinar cell vacuolation of the submandibular gland in the females; and lymphocyte infiltration in renal cortex and pelvis, and vacuolation of cerebellar white matter were noted in the males. The results of the present study indicate that long-term administration of APS does not exert tumorigenic or any other toxic actions in B6C3F1 mice.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
850 mg/kg bw/day
Study duration:
chronic
Species:
mouse

Carcinogenicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
carcinogenicity: 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:
according to guideline
Guideline:
EPA OPP 83-5 (Combined Chronic Toxicity / Carcinogenicity)
GLP compliance:
not specified
Species:
other: rats and guinea pigs
Strain:
other: rats Fischer 344 and guinea pigs (Hartley)
Sex:
male/female
Details on test animals or test system and environmental conditions:
rats (Fischer 344 males and females) and guinea pigs (Hartley)
Route of administration:
inhalation: dust
Type of inhalation exposure (if applicable):
whole body
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.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
six months
Frequency of treatment:
5 d/wk 6 hr/d
Remarks:
Doses / Concentrations:
0.25, 2.5, and 25 mg/m3 of aluminum chlorhydrate (ACH)
Basis:
actual ingested
Control animals:
yes
Details on study design:
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.
Observations and examinations performed and frequency:
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.
Sacrifice and pathology:
The pathology was characterized by an increase in mononuclear inflammatory cells and large macrophages in alveoli around the termination of air passage ways. These data suggest a progression in the inflammatory response of the lungs with aluminium chlorohydrate exposure that may be related to the tissue response to foreign bodies and the associated irritant response.
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:
effects observed, treatment-related
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:
effects observed, treatment-related
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:
This study reported a dose-related increase in lung lesions in both rats (Fischer 344 males and females) and guinea pigs (Hartley) following inhalation of aluminium chlorhydrate for six months. Fifty-percent of the animals showed lesions following exposure to 2.5 mg/Al/m3 increasing to 100% of animals that had been exposed to 25 mg Al/m3. In guinea pigs, approximately 10% showed an increase in AM at a low dose of 0.25 mg Al/m3. The pathology was characterized by an increase in mononuclear inflammatory cells and large macrophages in alveoli around the termination of air passage ways. These data suggest a progression in the inflammatory response of the lungs with aluminium chlorohydrate exposure that may be related to the tissue response to foreign bodies and the associated irritant response.
Relevance of carcinogenic effects / potential:
Respiratory effects: An increase in the number of alveolar macrophages and granulomatous lesions in the lungs and peribronchial lymph nodes were observed in rats and guinea pigs exposed to 0.61 or 6.1 mg Al/m3 aluminum chlorhydrate for 6 hours/day, 5 days/week for 6 months.
The severity of the alterations was concentration-related. In addition, statistically significant increases in absolute and relative lung weight were observed in the rats exposed to 6.1 mg Al/m3;
The authors noted that pulmonary edema was not observed in these rats. No statistically significant histological alterations or changes in lung weight were observed at 0.061 mg Al/m3.
Dose descriptor:
NOAEL
Effect level:
6.1 mg/m³ air
Sex:
male/female
Basis for effect level:
other: see 'Remark'
Remarks on result:
other: Effect type: carcinogenicity (migrated information)

Cardiovascular effects: No histological alterations were observed in the hearts of Fischer 344 rats or Hartley guinea pigs exposed by inhalation (6 hours/day, 5 days/week) to 6.1 mg Al/m3 as aluminum chlorhydrate for 6 months.

Gastrointestinal Effects: No histological changes were observed in the gastrointestinal tissues of Fischer 344 rats or Hartley guinea pigs exposed by inhalation (6 hours/day, 5 days/week) to 6.1 mg Al/m3 as aluminum chlorhydrate for 6 months.

Hematological Effects: No hematological effects were observed in Fischer 344 rats or Hartley guinea pigs exposed by inhalation (6 hours/day, 5 days/week) to 6.1 mg Al/m3 as aluminum chlorhydrate for 6 months.

Musculoskeletal Effects: No histological changes were observed in the muscle or bone of Fischer 344 rats or Hartley guinea pigs exposed by inhalation (6 hours/day, 5 days/week) to 6.1 mg Al/m3 as aluminum chlorhydrate for 6 months.

Hepatic Effects: No histological or organ weight changes were observed in livers of Fischer 344 rats or Hartley guinea pigs exposed by inhalation (6 hours/day, 5 days/week) to 6.1 mg Al/m3 as aluminum chlorhydrate for 6 months.

Renal Effects:No histological or organ weight changes were observed in kidneys of Fischer 344 rats or Hartley guinea pigs exposed by inhalation (6 hours/day, 5 days/week) to 6.1 mg Al/m3 as aluminum chlorhydrate for 6 months.

Endocrine Effects: No adverse histological changes were observed in the adrenal, thyroid, or pituitary glands of Fischer 344 rats or Hartley guinea pigs exposed by inhalation (6 hours/day, 5 days/week) to 6.1 mg Al/m3 as aluminum chlorhydrate for 6 months.

Dermal Effects: No histologic changes of the skin were observed in Fischer 344 rats or Hartley guinea pigs exposed by inhalation to 6.1 mg Al/m3 as aluminum chlorhydrate for 6 months.

Ocular Effects: No histological changes were observed in the eyes of Fischer 344 rats or Hartley guinea pigs exposed by inhalation to 6.1 mg Al/m3 as aluminum chlorhydrate for 6 months.

Body Weight Effects: No body weight effects were observed in Fischer 344 rats or Hartley guinea pigs exposed by inhalation to 6.1 mg Al/m3 as aluminum chlorhydrate for 6 months.

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.

Conclusions:
This study reported a dose-related increase in lung lesions in both rats (Fischer 344 males and females) and guinea pigs (Hartley) following inhalation of aluminium chlorhydrate for six months. Fifty-percent of the animals showed lesions following exposure to 2.5 mg/Al/m3 increasing to 100% of animals that had been exposed to 25 mg Al/m3. In guinea pigs, approximately 10% showed an increase in AM at a low dose of 0.25 mg Al/m3. The pathology was characterized by an increase in mononuclear inflammatory cells and large macrophages in alveoli around the termination of air passage ways. These data suggest a progression in the inflammatory response of the lungs with aluminium chlorohydrate exposure that may be related to the tissue response to foreign bodies and the associated irritant response.
Executive summary:

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.

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
6.1 mg/m³
Study duration:
chronic
Species:
rat

Carcinogenicity: via dermal route

Link to relevant study records
Reference
Endpoint:
carcinogenicity: oral
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:
according to guideline
Guideline:
EPA OPPTS 870.4300 (Combined Chronic Toxicity / Carcinogenicity)
GLP compliance:
not specified
Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals or test system and environmental conditions:
B6C3F1 mice (60 males and 60 females per group)
Route of administration:
oral: feed
Type of inhalation exposure (if applicable):
whole body
Vehicle:
unchanged (no vehicle)
Details on exposure:
Administration of aluminium potassium sulphate (APS) to B6C3F1 mice (60 males and 60 females per group) at levels of 1,2.5, 5 or 10% in the diet for 20 months (equivalent to 1500, 3750, 7500 or 15000 mg/kgbw/day of aluminium potassium sulphate and 85, 213, 427 or 853 mg Al/kg bw/day).One group receiving the basal diet served as the control.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
20 months
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
0, 2.5, 5.0 and 10.0% (w/w).
Basis:
nominal in diet
No. of animals per sex per dose:
B6C3F1 mice (60 males and 60 females per group)
Control animals:
yes
Details on study design:
This study involved the administration of aluminium potassium sulphate (APS) to B6C3F1 mice (60 males and 60 females per group) at levels of 1,2.5, 5 or 10% in the diet for 20 months (equivalent to 1500, 3750, 7500 or 15000 mg/kgbw/day of aluminium potassium sulphate and 85, 213, 427 or 853 mg Al/kg bw/day).
Positive control:
One group receiving the basal diet served as the control.
Observations and examinations performed and frequency:
This study involved the administration of aluminium potassium sulphate (APS) to B6C3F1 mice (60 males and 60 females per group) at levels of 1,2.5, 5 or 10% in the diet for 20 months (equivalent to 1500, 3750, 7500 or 15000 mg/kgbw/day of aluminium potassium sulphate and 85, 213, 427 or 853 mg Al/kg bw/day).
Body weight gain was reduced in the mice receiving 10% APS and increased in the groups receiving1 or 2.5%, while those receiving 5% showed similar weight gains to controls.
Survival rates were marginally increased in all APS-treated mice compared with controls, and there was noevidence of Al-related toxicity in any of the treated groups. There was also no increase in the incidence of gross tumours, neoplastic lesions, or other proliferative lesions in treated micecompared with controls. Animals receiving 10% APS in the diet showed asignificantly lowerincidence in total tumours compared with controls, which was mainly attributable to areduction in the incidence of hepatocellular carcinoma, although incidence of other tumourssuch as pulmonary adenocarcinoma and Harderian gland adenomas were also reduced. The lower tumour incidence was in turn attributed to the reduced body weight gain seen in animalsat this dose level. The authors concluded that there was no evidence of tumourogenicity or anyother toxic actions of APS in B6C3F1 mice in this study
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
In the tumor pathology, the incidence of hepatocellular carcinoma was significantly decreased in the males in the 10% APS treated group.
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
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
Details on results:
This study showed no increase in the incidence of gross tumours, neoplastic lesions, or other proliferative lesions in B6C3F1 mice following dietary exposure to up to 850 mg Al/kg/day for 20-24 months. Interestingly, in all groups, the incidence of spontaneous hepatocellular carcinoma was significantly decreased in the females. This was also significantly decreased in the high-dose group males (5.5 vs. 20.5% in controls) and the incidence of myocardial eosinophilic cytoplasm showed a dose-dependent decrease with aluminium exposure.

Dose descriptor:
NOAEL
Effect level:
850 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: see 'Remark'
Remarks on result:
other: Effect type: carcinogenicity (migrated information)

A more recent study byOneda et al. (1994)showed no increase in the incidence of gross tumours, neoplastic lesions, or other proliferative lesions in B6C3F1mice following dietary exposure to up to 979 mg Al/kg/day for 20-24 months. Interestingly, in all groups, the incidence of spontaneous hepatocellular carcinoma was significantly decreased in the females. This was also significantly decreased in the high-dose group males (5.5 vs. 20.5% in controls) and the incidence of myocardial eosinophilic cytoplasm showed a dose-dependent decrease with aluminium exposure.
Conclusions:
This study for B6C3F1 mouse did not however indicate any carcinogenic potential of aluminium potassium sulphate at levels of up to 850 mg Al/kg bw/day in the diet. The Panel also noted the absence of epidemiological evidence for carcinogenicity of aluminium compounds used therapeutically, and the conclusion of IARC that aluminium itself is unlikely to be a human carcinogen, despite the observation of an association between inhalation exposure to aluminium dust and aluminium compounds during production/processing and cancer in workers.
Executive summary:

The tumorigenic potential of aluminum potassium sulfate [A1K (SO4)2 12H2O, APS], a compound which exists widely in the environment, was investigated in B6C3F1 mice. APS was administered in the diet for 20 months at dose levels of 1.0, 2.5, 5.0 and 10.0% (w/w). One group receiving the basal diet served as the control. Body weight gain in both sexes was decreased in the 10.0% APS treated group, and increased in the 1.0 and 2.5% APS treated groups. 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 APS treated groups. The survival rate showed a tendency to increase in both sexes in all the APS treated groups. In the tumor pathology, the incidence of hepatocellular carcinoma was significantly decreased in the males in the 10% APS treated group. The incidence of hepatocellular carcinoma was significantly decreased in females in all groups including the control group. As regards the nontumorous pathology, the incidence of myocardial eosinophilic cytoplasm showed a significant dose-dependent decrease in males in the APS treated groups. A comparison between the sexes revealed a significant decrease in the incidence of hepatocytic anisonucleosis, myocardial eosinophilic cytoplasm and acinar cell vacuolation of the submandibular gland in the females; and lymphocyte infiltration in renal cortex and pelvis, and vacuolation of cerebellar white matter were noted in the males. The results of the present study indicate that long-term administration of APS does not exert tumorigenic or any other toxic actions in B6C3F1 mice.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
6.8 mg/kg bw/day
Study duration:
chronic
Species:
mouse

Justification for classification or non-classification

Based on the hazard assessmentof 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

Carcinogenicity

Carc. Cat. 1; R45 May cause cancer.

Carc. Cat. 1; R49 May cause cancer by inhalation.

Carc. Cat. 2; R45 May cause cancer.

Carc. Cat. 2; R49 May cause cancer by inhalation.

Carc. Cat. 3; R40 Limited evidence of a carcinogenic effect.

 

CLP

Carcinogenicity

Carc. 1A

Carc. 1B

Carc. 2

H350: May cause cancer <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

H351: Suspected of causing cancer <state route of exposure if it is conclusively proven that no other routs 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 Carcinogenicity.

 

Additional information

The literature concerning oral exposure bioassays is very limited. An increase in gross tumours was reported in male rats and female mice in a one-dose study but few study details were reported (Schroeder and Mitchener 1975a, 1975b, as reported in ATSDR 2006). Two other studies reported no increased incidence of tumours in rats and mice exposed orally to aluminum compounds (Hackenberg 1972; Oneda et al. 1994).

No increased tumour incidence was observed in rats following inhalation of alumina fibres at concentrations of up to 2.45 mg/m3 ( Pigott GH et al.1981, Krewski et al. 2007).

The International Agency for Research on Cancer did not classify specific aluminum compounds for carcinogenicity, but classified the exposure circumstances of aluminum production as carcinogenic to humans (Group 1) (IARC 1987).

For dermal exposure we taken that:

-the average weight of mouse is 80 g .

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

corrected dermal NOAEL= oral NOAEL

850 mg/kg bw/day * 0.008 kg =

NOAELmouse 6.8 mg/kg bw/day

 

 


Justification for selection of carcinogenicity via dermal route endpoint:
For dermal exposure we taken that:
-the average weight of mouse is 80 g .
-the dose is applied over an area which is approximately 10% of the total body surface=0.008 kg
corrected dermal NOAEL= oral NOAEL
850 mg/kg bw/day * 0.008 kg =
NOAELmouse 6.8 mg/kg bw/day

Carcinogenicity: via oral route (target organ): other: all gross lesions and masses

Carcinogenicity: via inhalation route (target organ): respiratory: lung

Carcinogenicity: via dermal route (target organ): other: all gross lesions and masses