Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.2 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
1 233.47 mg/m³
Explanation for the modification of the dose descriptor starting point:

Long term inhalation studies are not available. The long term systemic DNEL for inhalation has been derived from a combined reproduction/developmental screening study.

For derivation of the dose descriptor starting point a factor of 2 has been included for route-to-route extrapolation from oral to inhalative.

AF for dose response relationship:
1
Justification:
Default ECHA AF for NOAEL used as starting point.
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic.
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:
2.5
Justification:
Default assessment factor for remaining differences.
AF for intraspecies differences:
5
Justification:
Default assessment factor for intraspecies differences.
AF for the quality of the whole database:
1
Justification:
The key study was conducted according to modern regulatory standards and was adequately reported. The database is not considered to contribute uncertainty, no additional factor needed.
AF for remaining uncertainties:
2
Justification:
An additional AF of 2 has been included taking account of remaining uncertainties due to read-across.
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:
2.33 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Long term studies are not available. The long term systemic DNEL for dermal exposure has been derived from a combined reproduction/developmental screening study.

AF for dose response relationship:
1
Justification:
Default ECHA AF for NOAEL used as starting point.
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Default correction factor for allometric scaling.
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for remaining differences.
AF for intraspecies differences:
5
Justification:
Default assessment factor for intraspecies differences.
AF for the quality of the whole database:
1
Justification:
The key study was conducted according to modern regulatory standards and was adequately reported. The database is not considered to contribute uncertainty, no additional factor needed.
AF for remaining uncertainties:
2
Justification:
An additional AF of 2 has been included taking account of remaining uncertainties due to read-across.
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

Selection of the relevant dose descriptors:

Oral:

NOAEL = 1000 mg/kg bw/day: derived from a subacute reproduction/developmental screening study according to OECD 422, rat, oral (gavage); read-across to Isostearic acid, esters with methyl-α-D-glucose. 

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

Oral absorption

The physicochemical properties of Isostearic acid, esters with methyl-α-D glucose (log Kow > 6.5) and the molecular weight of(weighted mean) 690.31g/mol in general do not favour absorption from the gastro-intestinal tract subsequent to oral ingestion (molecular weight > 500 g/mol, log Kow between > 4). However, since the substance is an UVCB partial absorption cannot be fully excluded. For chemical safety assessment an oral absorption rate of 50% is assumed as a worst case default value in the absence of other data

Dermal absorption

It is generally thought that substances with a high molecular weight (> 500 g/mol) and a high log Kow (> 6.5) are not readily dermally absorbed. Thus, dermal absorption of the source substance Isostearic acid, esters with methyl-α-D-glucose is considered to be low. The target substance alpha methyl glucoside exhibits a low molecular weight (194.183 g/mol) and a low log Kow (-2.5). Due to the low partition coefficient absorption of alpha methyl glucoside is also rather unlikely.

However, in the absence of detailed dermal penetration data it has to be assumed that for both substances dermal penetration may occur.

For chemical safety assessment a dermal absorption rate of 50% is assumed as a worst case default value.

 

Inhalation absorption

For chemical safety assessment an inhalation absorption rate of 100% is assumed for alpha methyl glucoside as a worst case default value in the absence of other data. By default, twice as high absorption is assumed compared to oral absorption (Guidance on Information Requirements and Chemical Safety Assessment, R8).

Extrapolation oral to inhalation: AF 2

 

DERIVATION OF DNELs

DNELs derived from subacute reproduction/developmental screening NOAEL (OECD guideline 422)

 

Worker-DNEL long-term for inhalation route (systemic): 8.2 mg/m³

Start value: 1000 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 1233.47 mg/m³

 

For workers the corrected inhalation NOEC is calculated according to the following equation:

corrected inhalation NOAEC  = oral NOAEL x 1/sRVrat x ABSoral-rat/ ABSinh-human x sRVhuman/ wRV

                                             = 1000 x 1/0.38 x 50/100 x 6.7/10 x 1.4

The corrected inhalation NOAEC worker (8h) is therefore:

                                             = 1233.47 mg/m³ (8h-TWA)

Overall AF: 1*6*1*2.5*5*1*2 = 150

 

This DNEL does not address the potential for local irritation. The risk characterisation will consider whether specific risk management measures are necessary to protect against local effects.

 

Worker-DNEL long-term for dermal route (systemic):  2.33 mg/kg bw/d

Start value: 1000 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 1000 mg/kg bw/d

Overall AF: 1*6*4*2.5*5*1*2 = 600

An additional factor of 2 was applied due to uncertainties from read-across.

For workers the corrected dermal NOAEL is calculated according to the following equation:

corrected dermal NOAEL = oral NOAEL x ABSoral-rat/ ABSderm-human x days per week (experimental)/days per week (human population; worker)

                                             = 1000 x 100/100 x 7/5

 The corrected dermal NOAEL worker (8h) is therefore:

                                        = 1400 mg/kg bw/d

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.45 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
435 mg/m³
Explanation for the modification of the dose descriptor starting point:

Long term studies are not available. The long term systemic DNEL for inhalation has been derived from a combined reproduction/developmental screening study. An additional factor of 2 was applied due to uncertainties from read-across.

AF for dose response relationship:
1
Justification:
Default ECHA AF for NOAEL used as starting point.
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic.
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:
2.5
Justification:
Default assessment factor for remaining differences.
AF for intraspecies differences:
10
Justification:
Default assessment factor intraspecies differences due to lack of data regarding pathways for metabolism.
AF for the quality of the whole database:
1
Justification:
The key study was conducted according to modern regulatory standards and was adequately reported. The quality of the database is not considered to contribute uncertainty, no additional factor needed.
AF for remaining uncertainties:
2
Justification:
An additional AF of 2 has been included taking account of remaining uncertainties due to read-across.
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:
0.833 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 200
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Long term studies are not available. The long term systemic DNEL for dermal exposure has been derived from a combined reproduction/developmental screening study. An additional factor of 2 was applied due to uncertainties from read-across.

AF for dose response relationship:
1
Justification:
Default ECHA AF for NOAEL used as starting point.
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Default corrections for respiratory rate and respiratory volume have been included in route-to-route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for remaining differences.
AF for intraspecies differences:
10
Justification:
Default assessment factor intraspecies differences due to lack of data regarding pathways for metabolism.
AF for the quality of the whole database:
1
Justification:
The key study was conducted according to modern regulatory standards and was adequately reported. The quality of the database is not considered to contribute uncertainty, no additional factor needed.
AF for remaining uncertainties:
2
Justification:
An additional AF of 2 has been included taking account of remaining uncertainties due to read-across.
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:
0.833 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 200
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Long term studies are not available. The long term systemic DNEL for oral exposure has been derived from a combined reproduction/developmental screening study. An additional factor of 2 was applied due to uncertainties from read-across.

AF for dose response relationship:
1
Justification:
Default ECHA AF for NOAEL used as starting point.
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Default correction factor for allometric scaling
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for remaining differences.
AF for intraspecies differences:
10
Justification:
Default assessment factor intraspecies differences due to lack of data regarding pathways for metabolism.
AF for the quality of the whole database:
1
Justification:
The key study was conducted according to modern regulatory standards and was adequately reported. The quality of the database is not considered to contribute uncertainty, no additional factor needed.
AF for remaining uncertainties:
2
Justification:
An additional AF of 2 has been included taking account of remaining uncertainties due to read-across.
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

Selection of the relevant dose descriptors:

Oral:

NOAEL = 1000 mg/kg bw/day: derived from a subacute reproduction/developmental screening study according to OECD 422, rat, oral (gavage); read-across to Isostearic acid, esters with methyl-α-D-glucose.

 

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

Oral absorption

The physicochemical properties of Isotearic acid, esters with methyl α D glucose (log Kow > 6.5) and the molecular weight of(weighted mean) 690.31g/mol in general do not favour absorption from the gastro-intestinal tract subsequent to oral ingestion (molecular weight > 500 g/mol, log Kow between > 4). However, since the substance is an UVCB partial absorption cannot be fully excluded. For chemical safety assessment an oral absorption rate of 50% is assumed as a worst case default value in the absence of other data

 

Dermal absorption

It is generally thought that substances with a high molecular weight (> 500 g/mol) and a high log Kow (> 6.5) are not readily dermally absorbed. Thus, dermal absorption of the source substance Isostearic acid, esters with methyl-α-D-glucose is considered to be low. The target substance alpha methyl glucoside exhibits a low molecular weight (194.183 g/mol) and a low log Kow (-2.5). Due to the low partition coefficient absorption of alpha methyl glucoside is also rather unlikely.

However, in the absence of detailed dermal penetration data it has to be assumed that for both substances dermal penetration may occur.

For chemical safety assessment a dermal absorption rate of 50% is assumed as a worst case default value.

 

Inhalation absorption

For chemical safety assessment an inhalation absorption rate of 100% is assumed for alpha methyl glucoside as a worst case default value in the absence of other data. By default, twice as high absorption is assumed compared to oral absorption (Guidance on Information Requirements and Chemical Safety Assessment, R8).

Extrapolation oral to inhalation: AF 2

 

DERIVATION OF DNELs

DNELs derived from subacute reproduction/developmental screening NOAEL (OECD guideline 422)

 

General population-DNEL long-term for inhalation route (systemic): 1.45 mg/m³

Start value: 1000 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 435 mg/m³

 

For general population the corrected inhalation NOEC is calculated according to the following equation:

corrected inhalation NOAEC  = oral NOAEL x 1/sRVrat x ABSoral-rat/ ABSinh-human

                                             = 1000 x 1/1.15 x 50/100

 

The corrected inhalation NOAEC general population (24 h) is therefore:

                                             = 435 mg/m³ (24 h)

Overall AF: 1*2.5*10*6*1*1*2 = 300

An additional factor of 2 was applied due to uncertainties from read-across.

 

This DNEL does not address the potential for local irritation. The risk characterisation will consider whether specific risk management measures are necessary to protect against local effects.

 

general population-DNEL long-term for dermal route (systemic):  0.833 mg/kg bw/d

Start value: 1000 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 1000 mg/kg bw/d

Overall AF: 4*2.5*10*6*1*1*2 = 1200

A factor of 2 was applied due to uncertainties from read-across.

For general population the corrected dermal NOEAL is calculated according to the following equation:

corrected dermal NOAEL  = oral NOAEL x ABSoral-rat/ ABSderm-human

                                               = 1000 x 100/100

The corrected dermal NOAELgeneral population (24 h) is therefore:

                                             = 1000 mg/m³ (24 h)

 

general population-DNEL long-term for oral route (systemic):  0.833 mg/kg bw/d

Start value: 1000 mg/kg bw/d

Route of original study: oral

Overall AF: 1*6*4*2.5*10*1*2 = 1200

An additional factor of 2 was applied due to uncertainties from read-across.

This DNEL does not address the potential for local irritation. The risk characterisation will consider whether specific risk management measures are necessary to protect against local effects.