Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35.3 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):
25
Modified dose descriptor starting point:
NOAEC
Value:
882 mg/m³
Explanation for the modification of the dose descriptor starting point:
In the absence of an inhalation study, a corrected inhalation starting point is derived based on the oral NOAEL of 1000 mg/kg bw/d. The oral NOAEL is corrected for breathing rate (/0.38) and activity (*0.67), resulting in a corrected inhalation NOAEC of 882 mg/m3.
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
not required: already considered
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
default value (workers)
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
Justification:
default value
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
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:
10 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):
100
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
A study of repeated dose dermal toxicity is not available. Dermal absorption and oral absorption are assumed (worst case) to be equivalent). A corrected dermal NOAEL of 1000 mg/kg bw/d is therefore derived.
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
starting point derived from a rat study
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
default value (workers)
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
Justification:
default value
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

DNEL Derivation

Polyol PX is of low acute toxicity, is not an irritant or sensitiser. An OECD 408 study with Polyol PX reports no effects at the highest (limit) dose level tested of 1000 mg/kg bw/d. A study of developmental toxicity performed with Polyol PX which also reports maternal and developmental NOAELs of 1000 mg/kg bw/d. An overall NOAEL of 1000 mg/kg bw/d is therefore used as a PoD for DNEL derivation.

Inhalation DNELs

Systemic inhalation DNELs

In the absence of an inhalation study, a corrected inhalation starting point is derived from the oral NOAEL of 1000 mg/kg bw/d. The oral NOAEL is corrected for breathing rate (/0.38) and activity (*0.67), resulting in a corrected inhalation NOAEC of 882 mg/m3.

Applying individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 1 (for allometric scaling), 2.5 (for other interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) results in an overall assessment factor of 25. Applying the overall assessment factor to the corrected starting point results in a DNEL of 35.3 mg/m3.

The substance is of very low acute toxicity. No hazard is identified; a short-term systemic inhalation DNEL is not required.

Local inhalation DNELs

The substance is not classified as a skin or eye irritant and there is no evidence for respiratory irritation or sensitisation. In the absence of an identified hazard, a local inhalation DNEL is not derived.

Dermal DNELs

Systemic dermal DNELs

A study of repeated dose dermal toxicity is not available. Dermal absorption and oral absorption are assumed (worst case) to be equivalent). A corrected dermal NOAEL of 1000 mg/kg bw/d is therefore derived. Applying individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 4 (for allometric scaling), 2.5 (for other interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) results in an overall assessment factor of 100. Applying the overall assessment factor to the corrected starting point results in a DNEL of 10 mg/kg bw/d.

The substance is of very low acute toxicity. No hazard is identified; a short-term systemic dermal DNEL is not required.

Local dermal DNELs

The substance is not classified as a skin or eye irritant and there is no evidence for skin irritation or sensitisation. In the absence of an identified hazard, a local dermal DNEL is not derived.

Polyol PX is not classified as an eye irritant.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.7 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
Value:
435 mg/m³
Explanation for the modification of the dose descriptor starting point:
In the absence of an inhalation study, a corrected inhalation starting point is derived from the oral NOAEL of 1000 mg/kg bw/d. The oral NOAEL is corrected for breathing rate (/1.15), resulting in a corrected inhalation NOAEC of 435 mg/m3.
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
extrapolation from sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
not required: already considered
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
default value (general population)
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
Justification:
default value
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:
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
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
A study of repeated dose dermal toxicity is not available. Dermal absorption and oral absorption are assumed (worst case) to be equivalent. A corrected dermal NOAEL of 1000 mg/kg bw/d is therefore derived.
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
extrapolation from a sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
starting point derived from a rat study
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
default value (general population)
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
Justification:
default value
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:
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
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The starting point is derived from an oral study; correction is therefore not required.
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
extrapolation from a sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
starting point derived from a rat study
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
default value (general population)
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
Justification:
default value
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

DNEL Derivation

Polyol PX is of low acute toxicity, is not an irritant or sensitiser. An OECD 408 study with Polyol PX reports no effects at the highest (limit) dose level tested of 1000 mg/kg bw/d. A study of developmental toxicity performed with Polyol PX which also reports maternal and developmental NOAELs of 1000 mg/kg bw/d. An overall NOAEL of 1000 mg/kg bw/d is therefore used as a PoD for DNEL derivation.

Inhalation DNELs

Systemic inhalation DNELs

In the absence of an inhalation study, a corrected inhalation starting point is derived from the oral NOAEL of 1000 mg/kg bw/d. The oral NOAEL is corrected for breathing rate (/1.15), resulting in a corrected inhalation NOAEC of 435 mg/m3.

Applying individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 1 (for allometric scaling), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) results in an overall assessment factor of 50. Applying the overall assessment factor to the corrected starting point results in a DNEL of 8.7 mg/m3.

The substance is of very low acute toxicity. No hazard is identified; a short-term systemic inhalation DNEL is not required.

Local inhalation DNELs

The substance is not classified as a skin or eye irritant and there is no evidence for respiratory irritation or sensitisation. In the absence of an identified hazard, a local inhalation DNEL is not derived.

Dermal DNELs

Systemic dermal DNELs

A study of repeated dose dermal toxicity is not available. Dermal absorption and oral absorption are assumed (worst case) to be equivalent). A corrected dermal NOAEL of 1000 mg/kg bw/d is therefore derived.

Applying individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 4 (for allometric scaling), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) results in an overall assessment factor of 200. Applying the overall assessment factor to the corrected starting point results in a DNEL of 5 mg/kg bw/d.

The substance is of very low acute toxicity. No hazard is identified; a short-term systemic dermal DNEL is not required.

Local dermal DNELs

The substance is not classified as a skin or eye irritant and there is no evidence for skin irritation or sensitisation. In the absence of an identified hazard, a local dermal DNEL is not derived.

Oral DNELs

Systemic oral DNELs

The starting point is derived from an oral study; correction is therefore not required.

Applying individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 4 (for allometric scaling), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) results in an overall assessment factor of 200. Applying the overall assessment factor to the corrected starting point results in a DNEL of 5 mg/kg bw/d.

The substance is of very low acute toxicity. No hazard is identified; a short-term systemic oral DNEL is not required.

 

The substance is not classified as an eye irritant.