Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
24 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):
75
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 763 mg/m³
Explanation for the modification of the dose descriptor starting point:

The starting point for DNEL derivation is the NOAEL from the oral (sub-acute) screening study of 1000 mg/kg bw/d with the submission substance [2,3-epoxypropyl neodecanoate, oligomeric reaction products with cyclohexane-1,2-dicarboxylic anhydride and propylidenetrimethanol]. A corrected inhalation starting point (NOAEC) for workers is calculated by taking into account activity (*6.7/10) and breathing rate (/0.38); a corrected inhalation NOAEC of 1763 mg/m3 is therefore calculated. Based on the expert toxicokinetic assessment, the extent of inhalation and oral absorption is likely to be very low and considered to be equivalent.

AF for dose response relationship:
1
Justification:
A default assessment factor of 1 is used for dose-response relationship; the starting point is derived from a NOAEL.
AF for differences in duration of exposure:
6
Justification:
An assessment factor of 6 is used to account for differences in the duration of exposure; extrapolation from a sub-acute study to long-term exposure.
AF for interspecies differences (allometric scaling):
1
Justification:
An assessment factor for interspecies differences (allometric scaling) is not required; allometric factors are taken into account in derivation of the corrected (inhalation) starting point.
AF for other interspecies differences:
2.5
Justification:
A default assessment factor of 2.5 is used to account for other interspecies differences.
AF for intraspecies differences:
5
Justification:
A default assessment factor of 5 is used to account for intraspecies differences (workers).
AF for the quality of the whole database:
1
Justification:
A default assessment factor of 1 is used for database quality; the toxicological dataset is of good quality.
AF for remaining uncertainties:
1
Justification:
A default assessment factor of 1 is used as there are no significant remaining 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:
3.3 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):
300
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
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 for DNEL derivation is the NOAEL from the oral (sub-acute) screening study of 1000 mg/kg bw/d with the submission substance [2,3-epoxypropyl neodecanoate, oligomeric reaction products with cyclohexane-1,2-dicarboxylic anhydride and propylidenetrimethanol]. Based on the expert toxicokinetic assessment, the extent of dermal and oral absorption is likely to be very low and considered to be equivalent. A corrected (dermal) NOAEL of 1000 mg/kg bw/d is therefore calculated.

AF for dose response relationship:
1
Justification:
A default assessment factor of 1 is used for dose-response relationship; the starting point is derived from a NOAEL.
AF for differences in duration of exposure:
6
Justification:
An assessment factor of 6 is used to account for differences in the duration of exposure; extrapolation from a sub-acute study to long-term exposure.
AF for interspecies differences (allometric scaling):
4
Justification:
A default assessment factor of 4 is used to account for interspecies differences (allometric scaling); the starting point is derived from a rat study.
AF for other interspecies differences:
1
Justification:
A default assessment factor of 2.5 is used to account for other interspecies differences.
AF for intraspecies differences:
5
Justification:
A default assessment factor of 5 is used to account for intraspecies differences (workers).
AF for the quality of the whole database:
1
Justification:
A default assessment factor of 1 is used for database quality; the toxicological dataset is of good quality.
AF for remaining uncertainties:
1
Justification:
A default assessment factor of 1 is used as there are no significant remaining 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:
no hazard identified

Additional information - workers

The submission substance [2,3-epoxypropyl neodecanoate, oligomeric reaction products with cyclohexane-1,2 -dicarboxylic anhydride and propylidenetrimethanol] is of low acute oral toxicity, is not a skin or eye irritant or a skin sensitiser. The substance is not genotoxic and is of low repeated dose toxicity; a NOAEL of 1000 mg/kg bw/d is reported for an OECD 422 screening study. The starting point for DNEL derivation is the NOAEL from the oral (sub-acute) screening study of 1000 mg/kg bw/d.

Inhalation DNELs

Systemic inhalation DNELs

The starting point for DNEL derivation is the NOAEL from the oral (sub-acute) screening study of 1000 mg/kg bw/d with the submission substance. A corrected inhalation starting point (NOAEC) for workers is calculated by taking into account activity (*6.7/10) and breathing rate (/0.38); a corrected inhalation NOAEC of 1763 mg/m3 is therefore calculated. Based on the expert toxicokinetic assessment, the extent of inhalation and oral absorption is likely to be very low and considered to be equivalent. Individual assessment factors of 1 (for dose-response relationship), 6 (for exposure duration), 1 (for allometric scaling), 2.5 (for interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 75. Application of the overall assessment factor of 75 to the corrected inhalation NOAEC of 1763 mg/m3 results in a long-term systemic inhalation DNEL for workers of 24 mg/m3.

The submission substance is of low acute toxicity and does not require classification for acute oral toxicity. In the absence of any identified hazard, a short-term systemic inhalation DNEL is not derived for workers.

Local inhalation DNELs

There are no data on acute or repeated inhalation exposure for the submission substance; however the submission substance is not a skin or eye irritant and is therefore not predicted to be a respiratory irritant. In the absence of any identified hazard, long-term and short-term local inhalation DNELs are not derived for workers.

Dermal DNELs

Systemic dermal DNELs

The starting point for DNEL derivation is the NOAEL from the oral (sub-acute) screening study of 1000 mg/kg bw/d with the submission substance. Based on the expert toxicokinetic assessment, the extent of dermal and oral absorption is likely to be very low and considered to be equivalent. A corrected (dermal) NOAEL of 1000 mg/kg bw/d is therefore calculated. Individual assessment factors of 1 (for dose-response relationship), 6 (for exposure duration), 4 (for allometric scaling), 2.5 (for interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 300. Application of the overall assessment factor of 300 to the corrected dermal NOAEL of 1000 mg/kg bw/d results in a long-term systemic dermal DNEL for workers of 3.3 mg/kg bw/d.

The submission substance is of low acute oral toxicity and does not require classification for acute toxicity. In the absence of any identified hazard, a short-term systemic dermal DNEL is not derived for workers.

Local dermal DNELs

The submission substance is not a skin irritant or sensitiser. In the absence of any identified hazard, long-term and short-term local dermal DNELs are not derived for workers.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6 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):
150
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
870 mg/m³
Explanation for the modification of the dose descriptor starting point:

The starting point for DNEL derivation is the NOAEL from the oral (sub-acute screening study of 1000 mg/kg bw/d with the submission substance [2,3-epoxypropyl neodecanoate, oligomeric reaction products with cyclohexane-1,2-dicarboxylic anhydride and propylidenetrimethanol]. A corrected inhalation starting point (NOAEC) for the general population is calculated by taking into account activity breathing rate (/1.15); a corrected inhalation NOAEC of 870 mg/m3 is therefore calculated. Based on the expert toxicokinetic assessment, the extent of inhalation and oral absorption is likely to be very low and considered to be equivalent.

AF for dose response relationship:
1
Justification:
A default assessment factor of 1 is used for dose-response relationship; the starting point is derived from a NOAEL.
AF for differences in duration of exposure:
6
Justification:
An assessment factor of 6 is used to account for differences in the duration of exposure; extrapolation from a sub-acute study to long-term exposure.
AF for interspecies differences (allometric scaling):
1
Justification:
An assessment factor for interspecies differences (allometric scaling) is not required; allometric factors are taken into account in derivation of the corrected (inhalation) starting point.
AF for other interspecies differences:
2.5
Justification:
A default assessment factor of 2.5 is used to account for other interspecies differences.
AF for intraspecies differences:
10
Justification:
A default assessment factor of 10 is used to account for intraspecies differences (general population).
AF for the quality of the whole database:
1
Justification:
A default assessment factor of 1 is used for database quality; the toxicological dataset is of good quality.
AF for remaining uncertainties:
1
Justification:
A default assessment factor of 1 is used as there are no significant remaining 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:
1.7 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):
600
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
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 for DNEL derivation is the NOAEL from the oral (sub-acute) screening study of 1000 mg/kg bw/d with the submission substance [2,3-epoxypropyl neodecanoate, oligomeric reaction products with cyclohexane-1,2-dicarboxylic anhydride and propylidenetrimethanol]. Based on the expert toxicokinetic assessment, the extent of dermal and oral absorption is likely to be very low and considered to be equivalent. A corrected (dermal) NOAEL of 1000 mg/kg bw/d is therefore calculated.

AF for dose response relationship:
1
Justification:
A default assessment factor of 1 is used for dose-response relationship; the starting point is derived from a NOAEL.
AF for differences in duration of exposure:
6
Justification:
An assessment factor of 6 is used to account for differences in the duration of exposure; extrapolation from a sub-acute study to long-term exposure.
AF for interspecies differences (allometric scaling):
4
Justification:
A default assessment factor of 4 is used to account for interspecies differences (allometric scaling); the starting point is derived from a rat study.
AF for other interspecies differences:
2.5
Justification:
A default assessment factor of 2.5 is used to account for other interspecies differences.
AF for intraspecies differences:
10
Justification:
A default assessment factor of 10 is used to account for intraspecies differences (general population).
AF for the quality of the whole database:
1
Justification:
A default assessment factor of 1 is used for database quality; the toxicological dataset is of good quality.
AF for remaining uncertainties:
1
Justification:
A default assessment factor of 1 is used as there are no significant remaining 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:
1.7 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):
600
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 from the oral (sub-acute) screening study of 1000 mg/kg bw/d with the submission substance [2,3-epoxypropyl neodecanoate, oligomeric reaction products with cyclohexane-1,2-dicarboxylic anhydride and propylidenetrimethanol] and does not therefore require correction.

AF for dose response relationship:
1
Justification:
A default assessment factor of 1 is used for dose-response relationship; the starting point is derived from a NOAEL.
AF for differences in duration of exposure:
6
Justification:
An assessment factor of 6 is used to account for differences in the duration of exposure; extrapolation from a sub-acute study to long-term exposure.
AF for interspecies differences (allometric scaling):
4
Justification:
A default assessment factor of 4 is used to account for interspecies differences (allometric scaling); the starting point is derived from a rat study.
AF for other interspecies differences:
2.5
Justification:
A default assessment factor of 2.5 is used to account for other interspecies differences.
AF for intraspecies differences:
10
Justification:
A default assessment factor of 10 is used to account for intraspecies differences (general population).
AF for the quality of the whole database:
1
Justification:
A default assessment factor of 1 is used for database quality; the toxicological dataset is of good quality.
AF for remaining uncertainties:
1
Justification:
A default assessment factor of 1 is used as there are no significant remaining 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 submission substance [2,3-epoxypropyl neodecanoate, oligomeric reaction products with cyclohexane-1,2 -dicarboxylic anhydride and propylidenetrimethanol] is of low acute oral toxicity, is not a skin or eye irritant or a skin sensitiser. The substance is not genotoxic and is of low repeated dose toxicity; a NOAEL of 1000 mg/kg bw/d is reported for an OECD 422 screening study. The starting point for DNEL derivation is the NOAEL from the oral (sub-acute) screening study of 1000 mg/kg bw/d.

Inhalation DNELs

Systemic inhalation DNELs

The starting point for DNEL derivation is the NOAEL from the oral (sub-acute) screening study of 1000 mg/kg bw/d with the submission substance. A corrected inhalation starting point (NOAEC) for the general population is calculated by taking into and breathing rate (/1.15); a corrected inhalation NOAEC of 870 mg/m3 is therefore calculated. Based on the expert toxicokinetic assessment, the extent of inhalation and oral absorption is likely to be very low and considered to be equivalent. Individual assessment factors of 1 (for dose-response relationship), 6 (for exposure duration), 1 (for allometric scaling), 2.5 (for interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 150. Application of the overall assessment factor of 150 to the corrected inhalation NOAEC of 870 mg/m3 results in a long-term systemic inhalation DNEL for the general population of 6 mg/m3.

The submission substance is of low acute toxicity and does not require classification for acute oral toxicity. In the absence of any identified hazard, a short-term systemic inhalation DNEL is not derived for the general population.

Local inhalation DNELs

There are no data on acute or repeated inhalation exposure for the submission substance; however the submission substance is not a skin or eye irritant and is therefore not predicted to be a respiratory irritant. In the absence of any identified hazard, long-term and short-term local inhalation DNELs are not derived for the general population.

Dermal DNELs

Systemic dermal DNELs

The starting point for DNEL derivation is the NOAEL from the oral (sub-acute) screening study of 1000 mg/kg bw/d with the submission substance. Based on the expert toxicokinetic assessment, the extent of dermal and oral absorption is likely to be very low and considered to be equivalent. A corrected (dermal) NOAEL of 1000 mg/kg bw/d is therefore calculated. Individual assessment factors of 1 (for dose-response relationship), 6 (for exposure duration), 4 (for allometric scaling), 2.5 (for interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 600. Application of the overall assessment factor of 300 to the corrected dermal NOAEL of 1000 mg/kg bw/d results in a long-term systemic dermal DNEL for the general population of 1.7 mg/kg bw/d.

The submission substance is of low acute oral toxicity and does not require classification for acute toxicity. In the absence of any identified hazard, a short-term systemic dermal DNEL is not derived for the general population.

Local dermal DNELs

The submission substance is not a skin irritant or sensitiser. In the absence of any identified hazard, long-term and short-term local dermal DNELs are not derived for the general population.

Oral DNELs

Systemic oral DNELs

The starting point is from the oral (sub-acute) screening study of 1000 mg/kg bw/d with the submission substance and does not therefore require correction.

Individual assessment factors of 1 (for dose-response relationship), 6 (for exposure duration), 4 (for allometric scaling), 2.5 (for interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 600. Application of the overall assessment factor of 600 to the oral NOAEL of 1000 mg/kg bw/d results in a long-term systemic oral DNEL for the general population of 1.7 mg/kg bw/d.

The submission substance is of low acute oral toxicity and does not require classification for acute toxicity. In the absence of any identified hazard, a short-term

systemic oral DNEL is not derived for the general population.