Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.1 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):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
26.45 mg/m³
Explanation for the modification of the dose descriptor starting point:

Oral to inhalation:  Inhalatory N(L)OAEC= oral N(L)OAEL*(1/0.38 m3/kg/d)*0.67*(ABSoral/ABSinh.) = 30*(1/0.38 m3/kg/d)*0.67*(1/1) = 26.45 mg/m³

AF for dose response relationship:
1
Justification:
The dose descriptor is a NOAEL
AF for differences in duration of exposure:
2
Justification:
AF of 2 due to the fact that it is a spermatogenesis effect so AF of 1 for exposure duration but AF of 2 to cover for group size between 28d study and chronic study
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 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 the substance 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:
DNEL (Derived No Effect Level)
Value:
21.2 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
NOAEC
DNEL value:
264.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

Oral to Inhalation (Inhalatory N(L)OAEC= oral N(L)OAEL*(1/0.38 m3/kg/d)*0.67*(ABSoral/ABSinh.)) = 300 * (1/0.38)*0.67*(1/2) = 264.5 mg/m³

AF for dose response relationship:
1
Justification:
The dose descriptor is a NOAEL
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 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 the substance 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

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:
0.15 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEL
DNEL value:
7.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In the teratogenicity study, the rats were treated for 6h. Workers are exposed for a 8h working day therefore the corrected NOAEL = 10*6/8=7.5 mg/kg/day

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 rat. AF for exposure duration is not necessary since the experimental exposure covers adequately the pregnancy of the rat.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor for the rat
AF for other interspecies differences:
2.5
Justification:
There are no data 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 the substance 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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.55 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:
26.45 mg/m³
Explanation for the modification of the dose descriptor starting point:

Oral to inhalation:  Inhalatory N(L)OAEC= oral N(L)OAEL*(1/0.38 m3/kg/d)*0.67*(ABSoral/ABSinh.) = 30*(1/0.38 m3/kg/d)*0.67*(1/1) = 26.45 mg/m³

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is a NOAEL
AF for differences in duration of exposure:
2
Justification:
AF of 2 due to the fact that it is a spermatogenesis effect so AF of 1 for exposure duration but AF of 2 to cover for group size between 28d study and chronic study
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 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:
DNEL (Derived No Effect Level)
Value:
10.6 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
264.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

Oral to Inhalation (Inhalatory N(L)OAEC= oral N(L)OAEL*(1/0.38 m3/kg/d)*0.67*(ABSoral/ABSinh.)) = 300 * (1/0.38)*0.67*(1/2) = 264.5 mg/m³

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is a NOAEL
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 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

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:
developmental toxicity / teratogenicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
DNEL value:
7.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In the teratogenicity study, the rats were treated for 6h. Workers are exposed for a 8h working day therefore the corrected NOAEL = 10*6/8=7.5 mg/kg/day

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 rat. AF for exposure duration is not necessary since the experimental exposure covers adequately the pregnancy of the rat.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor for the rat
AF for other interspecies differences:
2.5
Justification:
There are no data 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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.15 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:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

no extrapolation

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is a NOAEL
AF for differences in duration of exposure:
2
Justification:
AF of 2 due to the fact that it is a spermatogenesis effect so AF of 1 for exposure du
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor for the rat
AF for other interspecies differences:
2.5
Justification:
There are no data 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:
medium hazard (no threshold derived)

Additional information - General Population

In an in vivo eye irritation study in rabbits, DMI caused serious eye damage and was classified as category 1 for eye effects. Therefore the substance is considered a medium hazard. No information on which to derive a threshold or minimal effect level is available.