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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.5 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
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
88 mg/m³
Explanation for the modification of the dose descriptor starting point:

The relevant starting point is the NOAEL of 100 mg/kg bw/d from the oral 90-day rat study with CAPA 2047A.  A corrected starting point (inhalation NOAEC) of 88 mg/m3 can be calculated based on activity and breathing rate, and for the relative extent of oral (50%) and inhalation absorption (100%).  

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):
1
Justification:
Not required: already accounted for
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default value for workers
AF for the quality of the whole database:
1
Justification:
Default value: good quality database
AF for remaining uncertainties:
1
Justification:
Default value: 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:
1 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
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The relevant starting point is the NOAEL of 100 mg/kg bw/d from the oral 90-day rat study with CAPA 2047A.  In the absence of data on the extent of dermal absorption, this is assumed to be equivalent to oral absorption (worst case default).  A corrected dermal starting point (NOAEL) of 100 mg/kg bw/d is calculated.  

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:
Default value: starting point is a rat study
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default value for workers
AF for the quality of the whole database:
1
Justification:
Default value: good quality database
AF for remaining uncertainties:
1
Justification:
Default value: 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

No acute toxicity data are available for CAPA 2047A (2 -oxepanone, polymer with 1,6 -hexanediol); however the substance is predicted to be of low acute toxicity, and is not predicted to cause skin or eye irritation or skin sensitisation. The substance is assumed not to be mutagenic based on read-across studies in vitro. A 90 -day repeated dose oral toxicity study performed with CAPA 2047A in the rat reports a NOAEL of 100 mg/kg bw/d, based on histopathology of the stomach and thymus at higher dose levels of 300 and 1000 mg/kg bw/d. Gastric histopathology seen at 300 and 1000 mg/kg bw/d represents a local (site of contact) effect and as such is not considered to be of direct relevance to the human risk assessment. Observations of small thymus and associated histopathology may represent a non-specific stress response rather than direct toxicity to this organ, but are taken into account for derivation of the study NOAEL. A NOAEL of 1000 mg/kg bw/d is determined for a developmental toxicity study performed in the rat with CAPA 2047A. The NOAEL of 100 mg/kg bw/d from the 90-day study is therefore the relevant starting point for DNEL derivation.

Worker DNEL derivation

Inhalation DNELs

Systemic inhalation DNELs

The relevant starting point is the NOAEL of 100 mg/kg bw/d from the oral 90-day rat study with CAPA 2047A. A corrected starting point (inhalation NOAEC) of 88 mg/m3 can be calculated based on activity and breathing rate, and for the relative extent of oral (50%) and inhalation absorption (100%). 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 differences) are used, resulting in an overall assessment factor of 25. Application of the overall assessment factor to the corrected starting point results in a long-term systemic DNEL of 3.5 mg/m3. Based on read-across CAPA 2047A is predicted to be of low acute toxicity and is not classified for acute toxicity. In the absence of any identified hazard, an acute systemic inhalation DNEL is not proposed.

Local inhalation DNELs

Based on read-across, CAPA 2047A is assumed not to be an irritant or sensitiser; therefore local effects on the repiratory tract are not predicted. Local inhalation DNELs are not proposed in the absence of any identified hazard.

Dermal DNELs

Systemic dermal DNELs

The relevant starting point is the NOAEL of 100 mg/kg bw/d from the oral 90-day rat study with CAPA 2047A. In the absence of data on the extent of dermal absorption, this is assumed to be equivalent to oral absorption (worst case default). A corrected dermal starting point (NOAEL) of 100 mg/kg bw/d is calculated. 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 differences) are used, resulting in an overall assessment factor of 100. Application of the overall assessment factor to the corrected starting point results in a long-term systemic DNEL of 1 mg/kg bw/d.

Based on read-across CAPA 2047A is predicted to be of low acute toxicity and is not classified for acute toxicity. In the absence of any identified hazard, an acute systemic dermal DNEL is not proposed.

Local dermal DNELs

Based on read-across, CAPA 2047A is assumed not to be a skin irritant or sensitiser; therefore local dermal effects are not predicted. Local dermal DNELs arenot proposed in the absence of any identified hazard.

Hazard for the eyes

Based on read-across, CAPA 2047A is not classified as an eye irritant. No hazard is identified.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.9 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:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
43 mg/m³
Explanation for the modification of the dose descriptor starting point:

The relevant starting point is the NOAEL of 100 mg/kg bw/d from the oral 90-day rat study with CAPA 2047A.  A corrected starting point (inhalation NOAEC) of 43 mg/m3 can be calculated based on breathing rate and for the relative extent of oral (50%) and inhalation absorption (100%).  

AF for dose response relationship:
1
Justification:
Default value
AF for differences in duration of exposure:
2
Justification:
Default value: extrapolation from a sub-chronic study to acute exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Not required (already taken into acount)
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: good quality dataset
AF for remaining uncertainties:
1
Justification:
Default value: 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:
0.5 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:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The relevant starting point is the NOAEL of 100 mg/kg bw/d from the oral 90-day rat study with CAPA 2047A.  In the absence of data on the extent of dermal absorption, this is assumed to be equivalent to oral absorption (worst case default).  A corrected dermal starting point (NOAEL) of 100 mg/kg bw/d is calculated.

AF for dose response relationship:
1
Justification:
Default value
AF for differences in duration of exposure:
2
Justification:
Default value: extrapolation from sub-chronic study to default exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default value: starting point is 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: good quality database
AF for remaining uncertainties:
1
Justification:
Default value: 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:
0.5 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:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Correction of the starting point is not required as this is derived from an oral study.

AF for dose response relationship:
1
Justification:
Default value
AF for differences in duration of exposure:
1
Justification:
Default value: extrapolation from sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default value: starting point is 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: good quality database
AF for remaining uncertainties:
1
Justification:
Default value: 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

No acute toxicity data are available for CAPA 2047A (2 -oxepanone, polymer with 1,6 -hexanediol); however the substance is predicted to be of low acute toxicity, and is not predicted to cause skin or eye irritation or skin sensitisation. The substance is assumed not to be mutagenic based on read-across in studies in vitro. A 90 -day repeated dose oral toxicity study performed with CAPA 2047A in the rat reports a NOAEL of 100 mg/kg bw/d, based on histopathology of the stomach and thymus at higher dose levels of 300 and 1000 mg/kg bw/d. Gastric histopathology seen at 300 and 1000 mg/kg bw/d represents a local (site of contact) effect and as such is not considered to be of direct relevance to the human risk assessment. Observations of small thymus and associated histopathology may represent a non-specific stress response rather than direct toxicity to this organ, but are taken into account for derivation of the study NOAEL. A NOAEL of 1000 mg/kg bw/d is determined for a developmental toxicity study performed in the rat with CAPA 2047A. The NOAEL of 100 mg/kg bw/d from the 90-day study is therefore the relevant starting point for DNEL derivation.

General Population DNEL derivation

Inhalation DNELs

Systemic inhalation DNELs

The relevant starting point is the NOAEL of 100 mg/kg bw/d from the 90-day oral rat study with CAPA 2047A. A corrected starting point (inhalation NOAEC) of 43 mg/m3 can be calculated based on breathing rate, and for the relative extent of oral (50%) and inhalation absorption (100%). 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 differences) are used, resulting in an overall assessment factor of 50. Application of the overall assessment factor to the corrected starting point results in a long-term systemic inhalation DNEL of 0.9 mg/m3.

Based on read-across CAPA 2047A is predicted to be of low acute toxicity and is not classified for acute toxicity. In the absence of any identified hazard, an acute systemic DNEL is not proposed.

Local inhalation DNELs

Based on read-across, CAPA 2047A is assumed not to be an irritant or sensitiser; therefore local effects on the respiratory tract are not predicted. Local inhalation DNELs are not proposed in the absence of any identified hazard.

Dermal DNELs

Systemic dermal DNELs

The relevant starting point is the NOAEL of 100 mg/kg bw/d from the 90-day oral rat study with CAPA 2047A. In the absence of data on the extent of dermal absorption, this is assumed to be equivalent to oral absorption (worst case default). A corrected dermal starting point (NOAEL) of 100 mg/kg bw/d is calculated. 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 differences) are used, resulting in an overall assessment factor of 200. Application of the overall assessment factor to the corrected starting point results in a long-term systemic dermal DNEL of 0.5 mg/kg bw/d.

Based on read-across CAPA 2047A is predicted to be of low acute toxicity and is not classified for acute toxicity. In the absence of any identified hazard, an acute systemic DNEL is not proposed.

Local dermal DNELs

Based on read-across, CAPA 2047A is assumed not to be a skin irritant or sensitiser; therefore local dermal effects are not predicted. Local dermal DNELs are not proposed in the absence of any identified hazard.

Oral DNELs

The relevant starting point is the NOAEL of 100 mg/kg bw/d from the 90-day oral rat study with CAPA 2047A. Correction of the starting point is not required. 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 differences) are used, resulting in an overall assessment factor of 200. Application of the overall assessment factor to the corrected starting point results in a long-term systemic oral DNEL of 0.5 mg/kg bw/d.

Based on read-across CAPA 2047A is predicted to be of low acute toxicity and is not classified for acute toxicity. In the absence of any identified hazard, an acute systemic DNEL is not proposed.

Hazard for the eyes

Based on read-across, CAPA 2047A is not classified as an eye irritant. No hazard is identified.