Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50.05 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
1 251.23 mg/m³
Explanation for the modification of the dose descriptor starting point:
The dose descriptor was corrected for exposure time difference and difference in respiratory volume: NOAEC corrected=2.49 x 6/8 x 6.7/10=1251.225 mg/m3
AF for dose response relationship:
1
Justification:
The dose descriptor is a NOAEL
AF for differences in duration of exposure:
2
Justification:
There is minimal difference between the effects following subacute (up to 28 days) and subchronic (up to 90 days) exposure to glycol ethers, either in qualitative or in quantitative terms (ECETOC TR95, 2005). Therefore a factor of 2 is justified for the duration extrapolation factor (subacute to chronic).
AF for interspecies differences (allometric scaling):
1
Justification:
Not applicable as inhalation DNEL
AF for other interspecies differences:
2.5
Justification:
There are no data for DEGDEE to quantify other differences between animals and humans that could affect interspecies extrapolation. On this basis a default factor of 2.5 to account for other species differences will also be applied.
AF for intraspecies differences:
5
Justification:
There are no data to quantify variability in susceptibility to the effects of long-term exposure to DEGDEE in the human population. The default factor of 5 for workers will therefore be used to take account of intraspecies differences.
AF for the quality of the whole database:
1
Justification:
The key study was part of a series of animal studies conducted to methods equivalent to modern regulatory standards. 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:
1
Justification:
No other uncertainties
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:
3.43 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):
87.5
Modified dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There is no data which indicates that the bioavailability or systemic absorbtion of DEGDEE is greater by the dermal route than by the oral route ; on this basis the NOEL from the oral study is used as the starting point for the dermal DNEL, without modification.
AF for dose response relationship:
1
Justification:
The dose descriptor starting point is a NOAEL
AF for differences in duration of exposure:
1
Justification:
The dose descriptor was obtained from a developmental study in the mouse. AF for exposure duration is not necessary since the experimental exposure covers adequately the pregnancy of the mouse.
AF for interspecies differences (allometric scaling):
7
Justification:
Allometric scaling factor for the mouse
AF for other interspecies differences:
2.5
Justification:
There are no data for DEGDEE to quantify other differences between animals and humans that could affect interspecies extrapolation. On this basis a default factor of 2.5 to account for other species differences will also be applied.
AF for intraspecies differences:
5
Justification:
There are no data to quantify variability in susceptibility to the effects of long-term exposure to DEGDEE in the human population. The default factor of 5 for workers will therefore be used to take account of intraspecies differences.
AF for the quality of the whole database:
1
Justification:
The key study was part of a series of animal studies conducted to methods equivalent to modern regulatory standards. 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:
1
Justification:
No other uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The guidance on dose/concentration response regarding human health (section R8.1.2.5 of chapter R.8 of the Guidance on Information Requirements and Chemical Safety Assessment) indicates that acute DNELs do not need to be calculated for substances that are not classified for an acute toxicity hazard. As this substance is not classified for acute toxicity hazards, no acute DNELs need to be calculated.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.96 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
DNEL value:
297.92 mg/m³
Explanation for the modification of the dose descriptor starting point:
The dose descriptor was corrected for exposure time difference and difference in respiratory volume: NOAEC corrected=2.49 x [(6x5)/(24x7)]x 6.7/10= 297.92 mg/m3
AF for dose response relationship:
1
Justification:
The dose descriptor is a NOAEL
AF for differences in duration of exposure:
2
Justification:
There is minimal difference between the effects following subacute (up to 28 days) and subchronic (up to 90 days) exposure to glycol ethers, either in qualitative or in quantitative terms (ECETOC TR95, 2005). Therefore a factor of 2 is justified for the duration extrapolation factor (subacute to chronic).
AF for interspecies differences (allometric scaling):
1
Justification:
Not applicable as inhalation DNEL
AF for other interspecies differences:
2.5
Justification:
There are no data for DEGDEE to quantify other differences between animals and humans that could affect interspecies extrapolation. On this basis a default factor of 2.5 to account for other species differences will also be applied.
AF for intraspecies differences:
10
Justification:
There are no data to quantify variability in susceptibility to the effects of long-term exposure to DEGDEE in the human population. The default factor of 10 for the general population will therefore be used to take account of intraspecies differences.
AF for the quality of the whole database:
1
Justification:
The key study was part of a series of animal studies conducted to methods equivalent to modern regulatory standards. 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:
1
Justification:
No other uncertainties
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:
1.71 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):
175
Modified dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There is no data which indicates that the bioavailability or systemic absorbtion of DEGDEE is greater by the dermal route than by the oral route ; on this basis the NOEL from the oral study is used as the starting point for the dermal DNEL, without modification.
AF for dose response relationship:
1
Justification:
The dose descriptor starting point is a NOAEL
AF for differences in duration of exposure:
1
Justification:
The dose descriptor was obtained from a developmental study in the mouse. AF for exposure duration is not necessary since the experimental exposure covers adequately the pregnancy of the mouse.
AF for interspecies differences (allometric scaling):
7
Justification:
Allometric scaling factor for the mouse
AF for other interspecies differences:
2.5
Justification:
There are no data for DEGDEE to quantify other differences between animals and humans that could affect interspecies extrapolation. On this basis a default factor of 2.5 to account for other species differences will also be applied.
AF for intraspecies differences:
10
Justification:
There are no data to quantify variability in susceptibility to the effects of long-term exposure to DEGDEE in the human population. The default factor of 10 for the general population will therefore be used to take account of intraspecies differences.
AF for the quality of the whole database:
1
Justification:
The key study was part of a series of animal studies conducted to methods equivalent to modern regulatory standards. 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:
1
Justification:
No other uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
1.71 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):
175
Modified dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not applicable
AF for dose response relationship:
1
Justification:
The dose descriptor starting point is a NOAEL
AF for differences in duration of exposure:
1
Justification:
The dose descriptor was obtained from a developmental study in the mouse. AF for exposure duration is not necessary since the experimental exposure covers adequately the pregnancy of the mouse.
AF for interspecies differences (allometric scaling):
7
Justification:
Allometric scaling factor for the mouse
AF for other interspecies differences:
2.5
Justification:
There are no data for DEGDEE to quantify other differences between animals and humans that could affect interspecies extrapolation. On this basis a default factor of 2.5 to account for other species differences will also be applied.
AF for intraspecies differences:
10
Justification:
There are no data to quantify variability in susceptibility to the effects of long-term exposure to DEGDEE in the human population. The default factor of 10 for the general population will therefore be used to take account of intraspecies differences.
AF for the quality of the whole database:
1
Justification:
The key study was part of a series of animal studies conducted to methods equivalent to modern regulatory standards. 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:
1
Justification:
No other 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:
no hazard identified

Additional information - General Population

The guidance on dose/concentration response regarding human health (section R8.1.2.5 of chapter R.8 of the Guidance on Information Requirements and Chemical Safety Assessment) indicates that acute DNELs do not need to be calculated for substances that are not classified for an acute toxicity hazard. As this substance is not classified for acute toxicity hazards, no acute DNELs need to be calculated.