Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.23 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
DNEL value:
261.72 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 the oral 90 day repeated dose toxicity 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. The original NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor for extrapolation from subchronic 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 interspecies differences
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers
AF for the quality of the whole database:
1
Justification:
The available studies were conducted according to modern regulatory standards and were adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
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:
1.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Long term studies with dermal exposure are not available. The long term systemic DNEL for dermal exposure has been derived from the oral subchronic repeated dose toxicity study.
AF for dose response relationship:
1
Justification:
Default ECHA AF for NOAEL used as starting point. The original NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor for extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to humans AF 4 (ECHA 2008).
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers
AF for the quality of the whole database:
1
Justification:
The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
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:
medium hazard (no threshold derived)

Additional information - workers

Selection of the relevant dose descriptors:

Oral:

NOAEL >/= 300 mg/kg bw/day: subchronic repeated dose toxicity study, rat, oral (gavage); read-across: C8-18 AAPB

 

NOEL = 300 mg/kg bw/d: prenatal developmental toxicity study, rat, oral (gavage); read-across: C8-18 AAPB

 

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

Oral absorption

No data exist on differences in bioavailability following oral or dermal exposure between experimental animals and humans, and a similar bioavailability is assumed by default.

 

Based on physicochemical properties and especially its ionic nature,Undecylenamidopropyl Betaine is expected to result in similarly low absorption (i.e. 10%) after oral or dermal administration or after inhalation.

 

Route-to-route extrapolation: oral to inhalation

For inhalation exposure, 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

 

Route-to-route extrapolation: oral to dermal

Although molecular weight (327.48 g/mol) and water solubility (3.1 g/L at 20°C) of the target substanceUndecylenamidopropyl Betaineare in a range suggesting dermal absorption, the low log Kow of -1.38 as well as the ionic naturesuggest that the substance is not likely to be sufficiently lipophilic to cross the stratum corneum, therefore dermal absorption is likely to be low.

For chemical safety assessment a dermal absorption rate of 10% is assumed. On the assumption that, in general, dermal absorption will not be higher than oral absorption, no AF (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation. (Guidance on Information Requirements and Chemical Safety Assessment, R8).

 

DERIVATION OF DNELs 

DNELs derived from subchronic repeated dose toxicity NOAEL (OECD guideline 408)

Worker-DNEL long-term for inhalation route (systemic): 5.23 mg/m³

Start value: 300 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 261.72 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

                                             = 300 x 1/0.384 x 50/100 x 6.7/10

The corrected inhalation NOAECworker(8h) is therefore:

                                             = 261.72 mg/m³ (8h-TWA)

Overall AF: 1*2.5*5*2*1*1*2 = 50

 

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):  1.5 mg/kg bw/d

Start value: 300 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 300 mg/kg bw/d

Overall AF 4*2.5*5*2*1*1*2 = 200

 

 

DNELs derived from prenatal developmental toxicity NOAEL (OECD guideline 414)

 

No assessment factor for time extrapolation is applied as the susceptible window is fully covered.

 

Worker-DNEL long-term for inhalation route (systemic): 10.46 mg/m³

Start value: 300 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 261.72 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

                                             = 300 x 1/0.384 x 50/100 x 6.7/10

 

The corrected inhalation NOAECworker(8h) is therefore:

                                             = 261.72 mg/m³ (8h-TWA)

Overall AF: 1*2.5*5*1*1*1*2 = 25

 

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):  3 mg/kg bw/d

Start value: 300 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 300 mg/kg bw/d

Overall AF 4*2.5*5*1*1*1*2 = 100

 

The DNELs for developmental toxicity are higher than those for repeated dose toxicity. Thus, the repeated dose toxicity-DNELs are also protective for development.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEC
DNEL value:
130.21 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 the oral 90 day repeated dose toxicity 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. The original NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor for extrapolation from subchronic 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 interspecies differences
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population
AF for the quality of the whole database:
1
Justification:
The available studies were conducted according to modern regulatory standards and were adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
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:
0.75 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
400
Modified dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Long term studies with dermal exposure are not available. The long term systemic DNEL for dermal exposure has been derived from the oral subchronic repeated dose toxicity study.
AF for dose response relationship:
1
Justification:
Default ECHA AF for NOAEL used as starting point. The original NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor for extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to humans AF 4 (ECHA 2008).
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population
AF for the quality of the whole database:
1
Justification:
The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
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:
0.75 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
400
Modified dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no route to route extrapolation required
AF for dose response relationship:
1
Justification:
Default ECHA AF for NOAEL used as starting point. The original NOAEL is reliable. No adjustment is required.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor for extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to humans AF 4 (ECHA 2008).
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population
AF for the quality of the whole database:
1
Justification:
The key study was conducted according to modern regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.
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:
medium hazard (no threshold derived)

Additional information - General Population

Selection of the relevant dose descriptors:

Oral:

NOAEL >/= 300 mg/kg bw/day: subchronic repeated dose toxicity study, rat, oral (gavage); read-across: C8-18 AAPB

 

NOEL = 300 mg/kg bw/d: prenatal developmental toxicity study, rat, oral (gavage); read-across: C8-18 AAPB

 

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

Oral absorption

No data exist on differences in bioavailability following oral or dermal exposure between experimental animals and humans, and a similar bioavailability is assumed by default.

 

Based on physicochemical properties and especially its ionic nature,Undecylenamidopropyl Betaine is expected to result in similarly low absorption (i.e. 10%) after oral or dermal administration or after inhalation.

 

Route-to-route extrapolation: oral to inhalation

For inhalation exposure, 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

 

Route-to-route extrapolation: oral to dermal

Although molecular weight (327.48 g/mol) and water solubility (3.1 g/L at 20°C) of the target substanceUndecylenamidopropyl Betaineare in a range suggesting dermal absorption, the low log Kow of -1.38 as well as the ionic naturesuggest that the substance is not likely to be sufficiently lipophilic to cross the stratum corneum, therefore dermal absorption is likely to be low.

For chemical safety assessment a dermal absorption rate of 10% is assumed. On the assumption that, in general, dermal absorption will not be higher than oral absorption, no AF (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation. (Guidance on Information Requirements and Chemical Safety Assessment, R8).

 

DERIVATION OF DNELs

DNELs derived from subchronic repeated dose toxicity NOAEL (OECD guideline 408)

General population-DNEL long-term for inhalation route (systemic): 1.3 mg/m³

Start value: 300 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 130.21 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

                                             = 300 x 1/1.152 x 50/100

 

The corrected inhalation NOAECgeneral population(24 h) is therefore:

                                             = 130.21 mg/m³ (24 h)

Overall AF: 1*2.5*10*2*1*1*2 = 100

 

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):  0.75 mg/kg bw/d

Start value: 300 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 300 mg/kg bw/d

Overall AF 4*2.5*10*2*1*1*2 = 400

 

General population-DNEL long-term for oral route (systemic):  0.75 mg/kg bw/d

Start value: 300 mg/kg bw/d

Route of original study: oral

Overall AF 4*2.5*10*2*1*1*2 = 400

 

 

DNELs derived from prenatal developmental toxicity NOAEL (OECD guideline 414)

 

No assessment factor for time extrapolation is applied as the susceptible window is fully covered.

 

General population-DNEL long-term for inhalation route (systemic): 2.6 mg/m³

Start value: 300 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 261.72 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

                                             = 300 x 1/1.152 x 50/100

 

The corrected inhalation NOAECgeneral population(24 h) is therefore:

                                             = 130.21 mg/m³ (24 h)

Overall AF: 1*2.5*10*1*1*1*2 = 50

 

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):  1.5 mg/kg bw/d

Start value: 300 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 300 mg/kg bw/d

Overall AF 4*2.5*10*1*1*1*2 = 200

 

General population-DNEL long-term for oral route (systemic):  1.5 mg/kg bw/d

Start value: 300 mg/kg bw/d

Route of original study: oral

Overall AF 4*2.5*10*1*1*1*2 = 200

 

The DNELs for developmental toxicity are higher than those for repeated dose toxicity. Thus, the repeated dose toxicity-DNELs are also protective for development.