Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.4 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
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
370 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for 2,2'-isopropylidenebis(p-phenyleneoxy)diethanol which is based upon a combined 28-day oral + reproduction/developmental toxicity screening (OECD 422). The NOAEL was established to 300 mg/kg bw/day. Therefore the corrected NOAEC is: NOAEL*(1/0.38)*(1/2)*(6.7/10)*1.4 = 370 mg/m3.

1/0.38 : standard respiratory volume

1/2 : factor 2route extrapolation from oral to inhalation

6.7/10 : differences of respiratory volume general population (8h)/ workers (8h)

7/5 :correction for differences in exposure schemes

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
4
Justification:
DNEL is based on an OECD 422 study. For an exposure of 28-day, ECHA recommends to use a factor of 6, and a factor of 2 for a 90-day study. In an OECD 422 study, rats were exposed approx. 6 weeks, thus a factor of 4 is appropriate.
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC calculation.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining differences.
AF for intraspecies differences:
5
Justification:
A factor of 5 is applied for workers
AF for the quality of the whole database:
1
Justification:
The key study chosen for DNEL calculation is considered as a reliable study.
AF for remaining uncertainties:
1
Justification:
no additional factor.
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
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for 2,2'-isopropylidenebis(p-phenyleneoxy)diethanol which is based upon a combined 28-day oral + reproduction/developmental toxicity screening (OECD 422). The NOAEL was established to 300 mg/kg bw/day. When applying the correction for differences between human and experimental exposure conditions (workers), the corrected NOAEL is : 300 x 1.4 = 420 mg/m3.

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL.
AF for differences in duration of exposure:
4
Justification:
DNEL is based on an OECD 422 study. For an exposure of 28-day, ECHA recommends to use a factor of 6, and a factor of 2 for a 90-day study. In an OECD 422 study, rats were exposed approx. 6 weeks, thus a factor of 4 is appropriate.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining difference.
AF for intraspecies differences:
5
Justification:
A factor of 5 is applied for worker DNELs.
AF for the quality of the whole database:
1
Justification:
The key study chosen for DNEL calculation is considered as a reliable study.
AF for remaining uncertainties:
1
Justification:
no additional factor
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:
1.3 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
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
130 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for 2,2'-isopropylidenebis(p-phenyleneoxy)diethanol which is based upon a combined 28-day oral + reproduction/developmental toxicity screening (OECD 422). The NOAEL was established to 300 mg/kg bw/day. Therefore the corrected NOAEC is: NOAEL*(1/1.15)*(1/2) = 130 mg/m3.

1/1.15: standard respiratory volume

1/2: factor 2route extrapolation from oral to inhalation

AF for dose response relationship:
1
Justification:
Starting poing is a NOAEL
AF for differences in duration of exposure:
4
Justification:
DNEL is based on an OECD 422 study. For an exposure of 28-day, ECHA recommends to use a factor of 6 and a factor of 2 for a 90-day study. In an OECD 422 study. In an OECD 422 study, rats were exposed approx. 6 weeks, thus a factor of 4 is appropriate.
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC calculation.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining differences.
AF for intraspecies differences:
10
Justification:
A factor of 10 is applied for general population.
AF for the quality of the whole database:
1
Justification:
The key study chosen for DNEL calculation is considered as a reliable study.
AF for remaining uncertainties:
1
Justification:
no additional factor
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
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for 2,2'-isopropylidenebis(p-phenyleneoxy)diethanol which is based upon a combined 28-day oral + reproduction/developmental toxicity screening (OECD 422). The NOAEL was established to 300 mg/kg bw/day. No correction factor should have to be applied.

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
4
Justification:
DNEL is based on an OECD 422 study. For an exposure of 28-day, ECHA recommends to use a factor of 6 and a factor of 2 for a 90-day study. In an OECD 422 study, rats were exposed approx. 6 weeks, thus a factor of 4 is appropriate.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining differences.
AF for intraspecies differences:
10
Justification:
A factor of 10 is applied for general population.
AF for the quality of the whole database:
1
Justification:
The key study chosen for DNEL calculation is considered as a reliable study
AF for remaining uncertainties:
1
Justification:
No additional factor
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
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for 2,2'-isopropylidenebis(p-phenyleneoxy)diethanol which is based upon a combined 28-day oral + reproduction/developmental toxicity screening (OECD 422). The NOAEL was established to 300 mg/kg bw/day. No correction factor should have to be applied.

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL.
AF for differences in duration of exposure:
4
Justification:
DNEL is based on an OECD 422 study. For an exposure of 28-day, ECHA recommends to use of 6 and a factor of 2 for a 90-day study. In an OECD 422 study, rats were exposed approx. 6 weeks, thus a factor of 4 is appropriate.
AF for interspecies differences (allometric scaling):
4
Justification:
A defeult factor for allometric scaling is 4 for rat to human.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining differences
AF for intraspecies differences:
10
Justification:
A factor of 10 is applied for general population.
AF for the quality of the whole database:
1
Justification:
The key study chosen for DNEL calculation is considered as a reliable study.
AF for remaining uncertainties:
1
Justification:
No additional factor
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