Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.38 mg/m³
Most sensitive endpoint:
neurotoxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC
Value:
51.89 mg/m³
Explanation for the modification of the dose descriptor starting point:
no reliable inhalation study available
AF for dose response relationship:
1
Justification:
default AF for starting point = NOAEL
AF for differences in duration of exposure:
1
Justification:
No time extrapolation factor has to be applied because the susceptible window is fully covered.
AF for interspecies differences (allometric scaling):
1
Justification:
default corrections for respiratory rate and respiratory volume have been included in route-to-route extrapolation
AF for other interspecies differences:
1
Justification:
No additional AF for other interspecies differences is used as Lactate is of no concern as it is part of the normal metabolism in most organisms and practically non-toxic, and Al as an element is not metabolised. There is no evidence that there are differences in toxicodynamics for Aluminium trilactate in different species. Thus, all intraspecies differences can be considered covered by allometric scaling.
AF for intraspecies differences:
5
Justification:
default AF (ECHA)
AF for the quality of the whole database:
1
Justification:
The available data are consistent and of high quality.
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
31.15 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):
35
Modified dose descriptor starting point:
NOAEL
Value:
1 090.4 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no dermal study available
AF for dose response relationship:
1
Justification:
default AF for starting point = NOAEL
AF for differences in duration of exposure:
1
Justification:
No time extrapolation factor has to be applied because the susceptible window is fully covered.
AF for interspecies differences (allometric scaling):
7
Justification:
allometric scaling factor mouse to human
AF for other interspecies differences:
1
Justification:
No additional AF for other interspecies differences is used as Lactate is of no concern as it is part of the normal metabolism in most organisms and practically non-toxic, and Al as an element is not metabolised. There is no evidence that there are differences in toxicodynamics for Aluminium trilactate in different species. Thus, all intraspecies differences can be considered covered by allometric scaling.
AF for intraspecies differences:
5
Justification:
default AF (ECHA)
AF for the quality of the whole database:
1
Justification:
The available data are consistent and of high quality.
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Time extrapolation:

No time extrapolation factor has to be applied because the susceptible window is fully covered in this neurodevelopmental toxicity study.

Route-to-route extrapolation:

Only tests with oral application are available. For the extrapolation oral to dermal toxicokinetic data are available. For the extrapolation oral to inhalative, the recommendations given in the Guidance on information requirements and chemical safety assessment are followed.

 

Modification of the relevant dose descriptors to the correct starting point:

Oral absorption

Oral bioavailability of Aluminium is in the range of 0.06 to 0.4% in rat and 0.57 to 2.18% in rabbit, depending on the presence of ligands: Al absorption is enhanced by organic ligands compared to inorganic ligands (Citrate > Tartrate, Gluconate, Lactate > Glutamate, Chloride, Sulphate, Nitrate). 1% is assumed for oral absorption as realistic worst case for Aluminium trilactate.

An adaptation for the differences in uptake of the different salts (Chloride, Sulphate, Citrate, Lactate, Nitrate) is not made here. Data from literature showed that GI absorption rates of several Al salts are all in the same order of magnitude, 1% and lower. A further adjustment would otherwise impart on the process a level of accuracy that is not supported by the scientific literature (see also Guidance on information requirements r7c).

 

allometric scaling: factor 7 (mouse to human)

The corrected oral NOAEL is 109.04 mg/kg bw/d/ 7 = 15.58 mg/kg bw/d

 

Oral to inhalatory

Based on the Guidance in information requirements and chemical safety assessment as well as data from EFSA (2008), 2% is assumed to to be a realistic worst case for inhalatory absorption, which is 200% of the oral bioavailability.

 

Oral to dermal

Uptake of Aluminium after dermal application is expected to be very limited. Based on an in vitro dermal absorption study, 0.1% is assumed to be systemically available after dermal application, which is 10% of the oral bioavailability.

 

allometric scaling: factor 7 (mouse to human)

The corrected dermal NOAEL is 109.04 mg/kg bw/d/ 7* 1 / 0.1 =155.77 mg/kg bw/d

Interspecies extrapolation, systemic effects:

- Lactate is of no concern as it is part of the normal metabolism in most organisms, practically non-toxic

- Aluminium as an element is not metabolised

Based on these facts, no differences in the toxicodynamics are expected, and thus the use of the additional factor of 2.5 is not justified.

Intraspecies variability worker:

Default factors proposed by ECHA are applied (5 for workers).

Worker-DNEL long-term for dermal route (systemic)

The following assessment factors were applied: 7 for allometric scaling, 5 for intraspecies variability worker. No time extrapolation factor has to be applied because the susceptible window is fully covered. This results in an overall assessment factor of 35.

1090.4 mg/kg bw/d /35 = 31.15 mg/kg bw/d

Worker-DNEL long-term for inhalatory route (systemic)

Start value: 109.04 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 51.89 mg/m³

 

inhalatory NOEC (8 h)             = oral NOAEL x 1/sRVratx ABSoral-rat/ ABSinh-humanx sRVhuman/ wRV

                                             = 109.04 x 1/0.384 x 50/100 x 6.7/10

The following assessment factors were applied: 5 for intraspecies variability worker. No addidional allometric scalin in required, default corrections for respiratory rate and respiratory volume have been included in route-to-route extrapolation. No time extrapolation factor has to be applied because the susceptible window is fully covered. This results in an overall assessment factor of 5.

51.89 mg/m³/5 = 10.38 mg/m³

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.58 mg/m³
Most sensitive endpoint:
neurotoxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Value:
25.81 mg/m³
Explanation for the modification of the dose descriptor starting point:
no reliable inhalation study available
AF for dose response relationship:
1
Justification:
default AF for starting point = NOAEL
AF for differences in duration of exposure:
1
Justification:
No time extrapolation factor has to be applied because the susceptible window is fully covered.
AF for interspecies differences (allometric scaling):
1
Justification:
default corrections for respiratory rate and respiratory volume have been included in route-to-route extrapolation
AF for other interspecies differences:
1
Justification:
No additional AF for other interspecies differences is used as Lactate is of no concern as it is part of the normal metabolism in most organisms and practically non-toxic, and Al as an element is not metabolised. There is no evidence that there are differences in toxicodynamics for Aluminium trilactate in different species. Thus, all intraspecies differences can be considered covered by allometric scaling.
AF for intraspecies differences:
10
Justification:
default AF (ECHA)
AF for the quality of the whole database:
1
Justification:
The available data are consistent and of high quality.
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
15.58 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):
70
Modified dose descriptor starting point:
NOAEL
Value:
1 090.4 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no dermal study available
AF for dose response relationship:
1
Justification:
default AF for starting point = NOAEL
AF for differences in duration of exposure:
1
Justification:
No time extrapolation factor has to be applied because the susceptible window is fully covered.
AF for interspecies differences (allometric scaling):
7
Justification:
allometric scaling factor mouse to human
AF for other interspecies differences:
1
Justification:
No additional AF for other interspecies differences is used as Lactate is of no concern as it is part of the normal metabolism in most organisms and practically non-toxic, and Al as an element is not metabolised. There is no evidence that there are differences in toxicodynamics for Aluminium trilactate in different species. Thus, all intraspecies differences can be considered covered by allometric scaling.
AF for intraspecies differences:
10
Justification:
default AF (ECHA)
AF for the quality of the whole database:
1
Justification:
The available data are consistent and of high quality.
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.56 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):
70
Modified dose descriptor starting point:
NOAEL
Value:
109.04 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no route to route extrapolation necessary
AF for dose response relationship:
1
Justification:
default AF for starting point = NOAEL
AF for differences in duration of exposure:
1
Justification:
No time extrapolation factor has to be applied because the susceptible window is fully covered.
AF for interspecies differences (allometric scaling):
7
Justification:
allometric scaling factor mouse to human
AF for other interspecies differences:
1
Justification:
No additional AF for other interspecies differences is used as Lactate is of no concern as it is part of the normal metabolism in most organisms and practically non-toxic, and Al as an element is not metabolised. There is no evidence that there are differences in toxicodynamics for Aluminium trilactate in different species. Thus, all intraspecies differences can be considered covered by allometric scaling.
AF for intraspecies differences:
10
Justification:
default AF (ECHA)
AF for the quality of the whole database:
1
Justification:
The available data are consistent and of high quality.
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

Time extrapolation:

No time extrapolation factor has to be applied because the susceptible window is fully covered in this neurodevelopmental toxicity study.

Route-to-route extrapolation:

Only tests with oral application are available. For the extrapolation oral to dermal toxicokinetic data are available. For the extrapolation oral to inhalative, the recommendations given in the Guidance on information requirements and chemical safety assessment are followed.

 

Modification of the relevant dose descriptors to the correct starting point:

Oral absorption

Oral bioavailability of Aluminium is in the range of 0.06 to 0.4% in rat and 0.57 to 2.18% in rabbit, depending on the presence of ligands: Al absorption is enhanced by organic ligands compared to inorganic ligands (Citrate > Tartrate, Gluconate, Lactate > Glutamate, Chloride, Sulphate, Nitrate). 1% is assumed for oral absorption as realistic worst case for Aluminium trilactate.

An adaptation for the differences in uptake of the different salts (Chloride, Sulphate, Citrate, Lactate, Nitrate) is not made here. Data from literature showed that GI absorption rates of several Al salts are all in the same order of magnitude, 1% and lower. A further adjustment would otherwise impart on the process a level of accuracy that is not supported by the scientific literature (see also Guidance on information requirements r7c).

 

allometric scaling: factor 7 (mouse to human)

The corrected oral NOAEL is 109.04 mg/kg bw/d/ 7 = 15.58 mg/kg bw/d

 

Oral to inhalatory

Based on the Guidance in information requirements and chemical safety assessment as well as data from EFSA (2008), 2% is assumed to to be a realistic worst case for inhalatory absorption, which is 200% of the oral bioavailability.

 

Oral to dermal

Uptake of Aluminium after dermal application is expected to be very limited. Based on an in vitro dermal absorption study, 0.1% is assumed to be systemically available after dermal application, which is 10% of the oral bioavailability.

 

allometric scaling: factor 7 (mouse to human)

The corrected dermal NOAEL is 109.04 mg/kg bw/d/ 7* 1 / 0.1 =155.77 mg/kg bw/d

Interspecies extrapolation, systemic effects:

- Lactate is of no concern as it is part of the normal metabolism in most organisms, practically non-toxic

- Aluminium as an element is not metabolised

Based on these facts, no differences in the toxicodynamics are expected, and thus the use of the additional factor of 2.5 is not justified.

Intraspecies variability general population:

Default factors proposed by ECHA are applied (10 for general population).

General population-DNEL long-term for oral route (systemic)

The following assessment factors were applied (REACH without AF 2.5): 7 for allometric scaling, 10 for intraspecies variability general population. No time extrapolation factor has to be applied because the susceptible window is fully covered. This results in an overall assessment factor of 70.

109.04 mg/kg bw/d /70 = 1.56 mg/kg bw/d

General population-DNEL long-term for inhalatory route (systemic)

Start value: 109.04 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 25.81 mg/m³

 

inhalatory NOEC (24 h)          = oral NOAEL x 1/sRVratx ABSoral-rat/ ABSinh-human

                                             =109.04x 1/1.152 x 50/100

The following assessment factors were applied: 10 for intraspecies variability worker.No addidional allometric scalin in required, default corrections for respiratory rate and respiratory volume have been included in route-to-route extrapolation.No time extrapolation factor has to be applied because the susceptible window is fully covered. This results in an overall assessment factor of 10.

25.81 mg/m³/10 = 2.58 mg/m³

  

General population-DNEL long-term for dermal route (systemic)

The following assessment factors were applied (REACH without AF 2.5): 7 for allometric scaling, 10 for intraspecies variability general population. No time extrapolation factor has to be applied because the susceptible window is fully covered. This results in an overall assessment factor of 70.

1090.4 mg/kg bw/d /70 = 15.58 mg/kg bw/d