Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13.4 mg/m³
Most sensitive endpoint:
neurotoxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
NOAEL
Value:
190 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
168 mg/m³
Explanation for the modification of the dose descriptor starting point:

For potential inhalation exposure, route-to-route extrapolation from the oral NOAEL value (30 mg/kg bw/d) of aluminium and therefore Aluminium sulphate (via aluminium citrate in a read-across approach) was performed.  As specific data for the starting route (oral) is determined (see Toxicokinetics section) and extrapolated data is assumed for the end route (inhalation),  assumptions have been made. Hence, it was determined that a  limited absorption of 1% occurs by the oral route, leading to a conservative internal NOAEL based on the conservative absorption rate (<<1% for aluminium citrate and aluminium sulphate in Priest's study). By comparison, a similar conservative rate of absorption is assumed for the inhalation route (i.e. 1%) leading to a maximal external NOAEL. Moreover, in the case of oral-to-inhalation extrapolation, it is proposed to include an additional  default factor of 2, i.e. the absorption percentage by oral route is half that of the inhalation absorption as suggested on page 19 of Guidance Document, Chapter R.8.  Finally, to convert the oral NOAEL into inhalatory NOAEC, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 0.38 m3/kg bw/8 h).  For workers a correction was added for the difference between respiratory rates under standard conditions (sRVhuman: 6.7 m3 for an 8-h exposure period) and under conditions of light activity (wRV: 10 m3 for an 8-h exposure period). Thus, for aluminium sulphate, the corrected dose descriptor for inhalation is 168 mg/m3 for workers considering a molecular mass of 342.1 g/Mol.

AF for dose response relationship:
1
Justification:
Based on NOAEL [ECHA default, Chapter R8 guidance].
AF for differences in duration of exposure:
1
Justification:
The study exposed the animals until they were 1 year of age.
AF for interspecies differences (allometric scaling):
1
Justification:
Not applicable for oral to inhalation extrapolation [ECHA default, Chapter R8 guidance].
AF for other interspecies differences:
2.5
Justification:
2.5 for remaining differences (rats to humans) [ECHA default, Chapter R8 guidance].
AF for intraspecies differences:
5
Justification:
ECHA default, Chapter R8 guidance for the worker
AF for the quality of the whole database:
1
Justification:
The available information as a whole meets the tonnage driven data requirement of REACH. Moreover, reliability and consistency are observed across the different studies.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.8 mg/kg bw/day
Most sensitive endpoint:
neurotoxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
Value:
190 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
190 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For potential dermal exposure, route-to-route extrapolation from the oral NOAEL value (30 mg Aluminium /kg bw/d) was performed. The oral absorption rate is below 1% (see Toxicokinetics section). Moreover, in the absence of specific data about dermal absorption and on the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor should be introduced when performing oral to dermal extrapolation (see Guidance Document, Chapter R.8, pp 19). Thus, it is assumed that  dermal absorption is not higher to 1%  for Aluminium sulphate. Then, applying a correction factor based on the ratio between the molecular mass of Aluminium ion (26,98 g/mL)  including two moles of Aluminium and Aluminium sulphate (342,1 g/mol),  the corrected starting descriptor for Aluminium sulphate  is 190 mg/kg bw/day for workers exposed by  dermal route.

AF for dose response relationship:
1
Justification:
Based on NOAEL [ECHA default, Chapter R8 guidance].
AF for differences in duration of exposure:
1
Justification:
The study exposed the animals until they were 1 year of age.
AF for interspecies differences (allometric scaling):
4
Justification:
4 for allometric scaling (rats to humans) [ECHA default, Chapter R8 guidance].
AF for other interspecies differences:
2.5
Justification:
Remaining differences between rat and human
AF for intraspecies differences:
5
Justification:
ECHA default, Chapter R8 guidance.
AF for the quality of the whole database:
1
Justification:
The available information as a whole meets the tonnage driven data requirement of REACH. Moreover, reliability and consistency are observed across the different studies.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.3 mg/m³
Most sensitive endpoint:
neurotoxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEL
Value:
190 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
83 mg/m³
Explanation for the modification of the dose descriptor starting point:

For potential inhalation exposure, route-to-route extrapolation from the oral NOAEL value (30 mg/kg bw/d) of Aluminium ion and therefore Aluminium sulphate (via aluminium citrate in a read-across approach) was performed.  As specific data for the starting route (oral) is determined (see Toxicokinetics section) and extrapolated data is assumed for the end route (inhalation),  assumptions have been made. Hence, it was determined that a  limited absorption of 1% occurs by the oral route, leading to a conservative internal NOAEL based on the conservative absorption rate (<<1% for aluminium citrate and aluminium sulphate in Priest's study). By comparison, a similar conservative rate of absorption is assumed for the inhalation route (i.e. 1%) leading to a maximal external NOAEL. Moreover, in the case of oral-to-inhalation extrapolation, it is proposed to include an additional  default factor of 2, i.e. the absorption percentage by oral route is half that of the inhalation absorption as suggested on page 19 of Guidance Document, Chapter R.8.  Finally, to convert the oral NOAEL into inhalatory NOAEC, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 1.15 m3/kg bw/24 h). Thus, for aluminium sulphate, the corrected dose descriptor  is 168 mg/m3 for general population exposed by considering a molecular mass of 342.1 g/Mol.

AF for dose response relationship:
1
Justification:
Based on NOAEL [ECHA default, Chapter R8 guidance].
AF for differences in duration of exposure:
1
Justification:
The study exposed the animals until they were 1 year of age.
AF for interspecies differences (allometric scaling):
1
Justification:
Not applicable for oral to inhalation extrapolation [ECHA default, Chapter R8 guidance].
AF for other interspecies differences:
2.5
Justification:
Remaining differences between rat and human.
AF for intraspecies differences:
10
Justification:
ECHA default, Chapter R8 guidance.
AF for the quality of the whole database:
1
Justification:
The available information as a whole meets the tonnage driven data requirement of REACH. Moreover, reliability and consistency are observed across the different studies.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.9 mg/kg bw/day
Most sensitive endpoint:
neurotoxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
Value:
190 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
190 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For potential dermal exposure, route-to-route extrapolation from the oral NOAEL value (30 mg Aluminium /kg bw/d) was performed. The oral absorption rate is below 1% for Aluminium sulphate (see Toxicokinetics section). Moreover, in the absence of specific data about dermal absorption and on the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor should be introduced when performing oral to dermal extrapolation (see Guidance Document, Chapter R.8, pp 19). Thus, it is assumed that dermal absorption is not higher to 1% for Aluminium sulphate. Then, applying a correction factor based on the ratio between the molecular mass of Aluminium ion (26,98 g/mL) including two moles of Aluminium and Aluminium sulphate (342,1 g/Mol), the corrected starting descriptor for Aluminium sulphate is 190 mg/kg bw/day for the general population exposed by dermal route.

AF for dose response relationship:
1
Justification:
Based on NOAEL [ECHA default, Chapter R8 guidance].
AF for differences in duration of exposure:
1
Justification:
The study exposed the animals until they were 1 year of age.
AF for interspecies differences (allometric scaling):
4
Justification:
4 for allometric scaling (rats to humans) [ECHA default, Chapter R8 guidance].
AF for other interspecies differences:
2.5
Justification:
Remaining differences between rat and human.
AF for intraspecies differences:
10
Justification:
ECHA default, Chapter R8 guidance.
AF for the quality of the whole database:
1
Justification:
The available information as a whole meets the tonnage driven data requirement of REACH. Moreover, reliability and consistency are observed across the different studies.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.9 mg/kg bw/day
Most sensitive endpoint:
neurotoxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
190 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
190 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For potential oral exposure,  extrapolation from the oral NOAEL value from Aluminium ion (30 mg/kg bw/d) was performed. The Aluminium sulphate oral absorption rate is below 1%  in animals (see Toxicokinetics section). Similar rate of absorption was observed in human.  Therefore, the oral absorption is considered at a maximum rate of 1% for Aluminium sulphate in human. Then, a correction factor based on the ratio between the molecular mass of Aluminium ion (26,98 g/mL)  including two moles of Aluminium and Aluminium sulphate (342,1 g/mol) was applied to extrapolate the corrected starting point for Aluminium sulphate to Aluminium ion. Finally, the corrected dose descriptor for oral route is 190 mg/kg bw/day for the general population.

AF for dose response relationship:
1
Justification:
Based on NOAEL [ECHA default, Chapter R8 guidance].
AF for differences in duration of exposure:
1
Justification:
The study exposed the animals until they were 1 year of age.
AF for interspecies differences (allometric scaling):
4
Justification:
4 for allometric scaling (rats to humans) [ECHA default, Chapter R8 guidance].
AF for other interspecies differences:
2.5
Justification:
Remaining differences between rat and human.
AF for intraspecies differences:
10
Justification:
ECHA default, Chapter R8 guidance.
AF for the quality of the whole database:
1
Justification:
The available information as a whole meets the tonnage driven data requirement of REACH. Moreover, reliability and consistency are observed across the different studies.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population