Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.8 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:
96.99 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
85.5 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 Dialuminium chloride pentahydroxide (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 in animals and in human, leading to a conservative internal NOAEL based on the conservative absorption rate (<<1% for aluminium citrate and dialuminium chloride pentahydroxide in a weight of evidence approach with aluminium chloride aluminium hydroxide tested 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 Dialuminium chloride pentahydroxide, the corrected dose descriptor for inhalation is 85.5 mg/m3 for workers considering a molecular mass of 174,45 g/mol together with the number of Aluminium mole for a mole of Dialuminium chloride pentahydroxide.

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:
Allometric scaling is not appropriate [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.
AF for remaining uncertainties:
1
Justification:
Reliability and consistency are observed across the different studies.
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:
1.94 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:
96.99 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
96.99 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 Dialuminium chloride pentahydroxide (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 Dialuminium chloride pentahydroxide. Then, applying a correction factor based on the ratio between the molecular mass of Aluminium ion (26,98 g/mL) and Dialuminium chloride pentahydroxide (174.45 g/mol) including two moles of Aluminium in the test substance, the corrected starting descriptor for Aluminium chloride basic is 96.99 mg/kg bw/day for the worker 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:
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 for worker, 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.
AF for remaining uncertainties:
1
Justification:
Reliability and consistency are observed across the different studies
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:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 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:
96.99 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
42.17 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 Dialuminium chloride pentahydroxide (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 in animals and in human, leading to a conservative internal NOAEL based on the conservative absorption rate (<<1% for aluminium citrate and dialuminium chloride pentahydroxide in a weight of evidence approach with aluminium chloride aluminium hydroxide tested 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 Dialuminium chloride pentahydroxide, the corrected dose descriptor for inhalation is 42.17 mg/m3 for the general population considering a molecular mass of 174,45 g/Mol together with the number of Aluminium mole in Dialuminium chloride pentahydroxide.

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 for the general population, 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.
AF for remaining uncertainties:
1
Justification:
Reliability and consistency are observed across the different studies.
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:
0.97 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:
96.99 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
96.99 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 Dialuminium chloride pentahydroxide (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 Dialuminium chloride pentahydroxide. Then, applying a correction factor based on the ratio between the molecular mass of Aluminium ion (26,98 g/mL) and Dialuminium chloride pentahydroxide (174.45 g/Mol) including two moles of Aluminium in the test substance, the corrected starting descriptor for Aluminium chloride basic is 96.99 mg/kg bw/day for the general population exposed by dermal route.

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:
1.2 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:
96.99 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
96.99 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The major route of exposure to aluminium for the  general population is through food. Mean concentrations of levels 5 to 10 mg/kg are found. Foods with very high mean concentrations included sources of natural origin e.g tea leaves, herbs and cocoa. Small amounts may come from food additives, and Al salts are also used in some pharmaceuticals, e.g over-the-counter medication against heartburn and effect enhances in injectable vaccins. On 2011, JECFA evaluated the new study described in the dossier (Developmental and One-Year Chronic Neurotoxicity Study of Aluminium Citrate in Rats). They considered that the developmental study provided a suitable and robust NOAEL for risk assessment (30 mg Al/kg bw/d). By appying the standard uncertainty factor of 100 to this NOAEL, the JECFA considered that it was appropriate to revise the provisional weekly tolerable intake (PTWI) upward to 2 mg Aluminium /kg bw/week. This corresponds to 6.46 mg Dialuminium chloride pentahydroxide/kg bw/week considering a molecular mass of 174.45 g/Mol for the salt. By calculation, an acceptable daily intake (ADI) can be extrapolated to 0.92 mg/kg bw/d for Dialuminium chloride pentahydroxide which is closed to the long-term DNEL for systemic effect by oral (1.2 mg/kg bw/d). SCCS (2014) agrees on the NOAEL of 30 mg Aluminium / kg bw/d used by JECFA for risk assessment. On 2008, Scientific opinion of the panel on food additive, flavourings, processing aids and food conctact materials estimated a daily dietary exposure to aluminium in the general population in several European countries varied to 0.2 to 1.5 mg Al/kg bw/week at the mean and was up to 2.3 mg Aluminium/kg bw/week in highly exposed consumers.

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:
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 for consumer, 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.
AF for remaining uncertainties:
1
Justification:
Reliability and consistency are observed across the different studies.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population