Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
18 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
DNEL value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
441 mg/m³
Explanation for the modification of the dose descriptor starting point:

The relevant starting point is the NOAEL of 500 mg/kg bw/d from the oral 90-day rat study with CAPA 2043.  A corrected starting point (inhalation NOAEC) of 441 mg/m3 can be calculated based on activity (*6.7/10) and breathing rate (/0.38), 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 chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Not required: allometric factors are already accounted for in derivation of the corrected starting point
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: a good quality database is available
AF for remaining uncertainties:
1
Justification:
Default value: 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:
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):
100
Dose descriptor starting point:
NOAEL
DNEL value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The relevant starting point is the NOAEL of 500 mg/kg bw/d from the oral 90 -day rat study with CAPA 2043.  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 500 mg/kg bw/d is therefore 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: the starting point is derived from 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: a good quality database is available
AF for remaining uncertainties:
1
Justification:
Default value: 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

CAPA 2043 (2 -oxepanone, polymer with 1,4-butanediol) is of low acute toxicity, is not classified for skin or eye irritation or for skin sensitisation. The substance is not mutagenic based on studies in vitro. A 90 -day repeated dose oral toxicity study performed with CAPA 2043 in the rat reports a NOAEL of 500 mg/kg bw/d.  A NOAEL of 800 mg/kg bw/d is determined for a developmental toxicity study performed in the rat with CAPA 2043. The NOAEL of 500 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 500 mg/kg bw/d from the oral 90-day rat study with CAPA 2043. A corrected starting point (inhalation NOAEC) of 441 mg/m3 can be calculated based on activity (*6.7/10) and breathing rate (/0.38), 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 18 mg/m3. CAPA 2043 is 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

CAPA 2043 is not 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 500 mg/kg bw/d from the oral 90 -day rat study with CAPA 2043. 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 500 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 5 mg/kg bw/d. CAPA 2043 is 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

CAPA 2043 is not 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.

Hazard for the eyes

CAPA 2043 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:
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
DNEL value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
217 mg/m³
Explanation for the modification of the dose descriptor starting point:

The relevant starting point is the NOAEL of 500 mg/kg bw/d from the oral 90-day rat study with CAPA 2043.  A corrected starting point (inhalation NOAEC) of 217 mg/m3 can be calculated based on breathing rate (/1.15) 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 chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Not required: allometric factors are already taken into acount in derivation of the corrected starting point
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: a good quality dataset is available
AF for remaining uncertainties:
1
Justification:
Default value: 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:
2.5 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
DNEL value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The relevant starting point is the NOAEL of 500 mg/kg bw/d from the oral 90-day rat study with CAPA 2043.  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 500 mg/kg bw/d is therefore 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 chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default value: the starting point is 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: a good quality database is available
AF for remaining uncertainties:
1
Justification:
Default value: 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:
2.5 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
DNEL value:
500 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
500 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:
2
Justification:
Default value: extrapolation from sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default value: the starting point is 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: a good quality database is available
AF for remaining uncertainties:
1
Justification:
Default value: 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

CAPA 2043 (2 -oxepanone, polymer with 1,4 -butanediol) is of low acute toxicity, is not classified for skin or eye irritation or for skin sensitisation. The substance is assumed not to be mutagenic based on studies in vitro. A 90 -day repeated dose oral toxicity study performed with CAPA 2043 in the rat reports a NOAEL of 500 mg/kg bw/d. A NOAEL of 800 mg/kg bw/d is determined for a developmental toxicity study performed in the rat with CAPA 2043.  The NOAEL of 500 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 500 mg/kg bw/d from the 90-day oral rat study with CAPA 2043. A corrected starting point (inhalation NOAEC) of 217 mg/m3 can be calculated based on breathing rate (/1.15), 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 4 mg/m3. CAPA 2043 is 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

CAPA 2043 is not 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 500 mg/kg bw/d from the 90-day oral rat study with CAPA 2043. 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 500 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 2.5 mg/kg bw/d. CAPA 2043 is 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

CAPA 2043 is not 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 500 mg/kg bw/d from the 90-day oral rat study with CAPA 2043. 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 2.5 mg/kg bw/d. CAPA 2043 is of low acute toxicity and is not classified for acute toxicity. In the absence of any identified hazard, an acute systemic oral DNEL is not proposed.

Hazard for the eyes

CAPA 2043 is not classified as an eye irritant. No hazard is identified.