ε-Caprolactone, oligomeric reaction products with propylidynetrimethanol

Toxicological Summary

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):

225

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

882 mg/m³

Explanation for the modification of the dose descriptor starting point:

is corrected for breathing rate (*6.7/10), activity (*1/0.38) and relative absorption (*1/2) to give a corrected inhalation NOAEC of 882 mg/m3

For CAPA 3050, the starting point of 1000 mg/kg bw/d from an oral rat study is corrected for activity breathing rate (*6.7/10), activity (*1/0.38) and relative absorption (*1/2) to give a corrected inhalation NOAEC of 882 mg/m3.

For CAPA 3050, the starting point of 1000 mg/kg bw/d from an oral rat study is corrected for activity breathing rate (*6.7/10), activity (*1/0.38) and relative absorption (*1/2) to give a corrected inhalation NOAEC of 882 mg/m3.

AF for dose response relationship:

1

Justification:

default value

AF for differences in duration of exposure:

6

Justification:

Standard factor: extrapolation from sub-acute study to chronic exposure

AF for interspecies differences (allometric scaling):

1

Justification:

not required: already considered in derivation of the corrected starting point

AF for other interspecies differences:

2.5

Justification:

Standard factor

AF for intraspecies differences:

5

Justification:

Standard factor for workers

AF for the quality of the whole database:

3

Justification:

In the absence of repeated dose toxicity studies assessing haematological, clinical chemistry or histopathology, an additional assessment factor of 3 for database quality is used for DNEL derivation. This additional factor is considered to be adequately protective based on the demonstrated low toxicity of related substances, components and metabolites of CAPA 3050.

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.1 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):

900

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:

In the absence of information on the extent of oral and dermal absorption, these are considered to be equivalent. The corrected dermal starting point is therefore 1000 mg/kg bw/d.

AF for dose response relationship:

1

Justification:

default value

AF for differences in duration of exposure:

6

Justification:

extrapolation from sub-acute study to chronic exposure

AF for interspecies differences (allometric scaling):

4

Justification:

default value (rat study used to derive the starting point)

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:

3

Justification:

In the absence of repeated dose toxicity studies assessing haematological, clinical chemistry or histopathology, an additional assessment factor of 3 for database quality is used for DNEL derivation. This additional factor is considered to be adequately protective based on the demonstrated low toxicity of related substances, components and metabolites of CAPA 3050.

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

The relevant starting point is the NOAEL of 1000 mg/kg bw/d from the rat developmental toxicity study performed with CAPA 3050; this study is considered to be a sub-acute study according to REACH Guidance. In the absence of repeated dose toxicity studies assessing haematological, clinical chemistry or histopathology, an additional assessment factor of 3 for database quality is used for DNEL derivation. This additional factor is considered to be adequately protective based on the demonstrated low toxicity of related substances, components and metabolites of CAPA 3050.

Inhalation DNELs

For workers, the starting point of 1000 mg/kg bw/d from the oral rat study is corrected for breathing volume (/0.38), activity (*0.67) and for the relative extent of oral and inhalation absorption (*0.5) to give a corrected (inhalation) starting point of 882 mg/m3.

Systemic inhalation DNELs

Assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure: extrapolation from sub-acute to chronic duration), 4 for allometric scaling, 2.5 (for interspecies differences), 5 (for intraspecies differences), 3 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 225. Application of the overall assessment factor to the corrected starting point gives a long-term systemic inhalation DNEL of 3.9 mg/m3 for workers. CAPA 3050 is not classified for acute toxicity. In the absence of any acute hazard, an acute systemic inhalation DNEL is not derived.

Local inhalation DNELs

CAPA 3050 is not an irritant or sensitiser. In the absence of any identified hazard, local inhalation DNEL values are not derived.

Dermal DNELs

In the absence of information on the extent of oral and dermal absorption, these are considered to be equivalent. The corrected dermal starting point is therefore 1000 mg/kg bw/d.

Systemic dermal DNELs

Assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure: extrapolation from sub-acute to chronic duration), 2.5 (for interspecies differences), 5 (for intraspecies differences), 3 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 900. Application of the overall assessment factor to the corrected starting point gives a long-term systemic dermal DNEL of 1.1 mg/kg bw/d for workers. CAPA 3050 is not classified for acute toxicity. In the absence of any acute hazard, an acute systemic dermal DNEL is not derived.

Local dermal DNELs

CAPA 3050 is not a skin irritant or sensitiser. In the absence of any identified hazard, local dermal DNEL values are not derived.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 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):

450

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

435 mg/m³

Explanation for the modification of the dose descriptor starting point:

For the general population, the starting point of 1000 mg/kg bw/d from an oral rat study is corrected for breathing volume (/1.15), and for the relative extent of oral and inhalation absorption (*0.5) to give a corrected (inhalation) starting point of 435 mg/m3.

AF for dose response relationship:

1

Justification:

default value

AF for differences in duration of exposure:

6

Justification:

extrapolation from a sub-acute study to chronic exposure

AF for interspecies differences (allometric scaling):

1

Justification:

not required: already taken into account in derivation of the modified 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:

3

Justification:

In the absence of repeated dose toxicity studies assessing haematological, clinical chemistry or histopathology, an additional assessment factor of 3 for database quality is used for DNEL derivation. This additional factor is considered to be adequately protective based on the demonstrated low toxicity of related substances, components and metabolites of CAPA 3050.

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:

0.6 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):

1 800

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:

In the absence of information on the extent of oral and dermal absorption, these are considered to be equivalent. The corrected dermal starting point is therefore 1000 mg/kg bw/d.

AF for dose response relationship:

1

Justification:

default value

AF for differences in duration of exposure:

6

Justification:

extrapolation from a sub-acute study to chronic exposure

AF for interspecies differences (allometric scaling):

4

Justification:

default value (rat study used to derive the 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:

3

Justification:

In the absence of repeated dose toxicity studies assessing haematological, clinical chemistry or histopathology, an additional assessment factor of 3 for database quality is used for DNEL derivation. This additional factor is considered to be adequately protective based on the demonstrated low toxicity of related substances, components and metabolites of CAPA 3050.

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:

0.6 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):

1 800

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:

Correction of the starting point is not required.

AF for dose response relationship:

1

Justification:

default value

AF for differences in duration of exposure:

6

Justification:

extrapolation from a sub-acute study to chronic exposure

AF for interspecies differences (allometric scaling):

4

Justification:

default value (rat study used to derive the 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:

3

Justification:

In the absence of repeated dose toxicity studies assessing haematological, clinical chemistry or histopathology, an additional assessment factor of 3 for database quality is used for DNEL derivation. This additional factor is considered to be adequately protective based on the demonstrated low toxicity of related substances, components and metabolites of CAPA 3050.

AF for remaining uncertainties:

1

Justification:

default value

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Modified dose descriptor starting point:

NOAEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

The relevant starting point is the NOAEL of 1000 mg/kg bw/d from the rat developmental toxicity study performed with CAPA 3050; this study is considered to be a sub-acute study according to REACH Guidance. In the absence of repeated dose toxicity studies assessing haematological, clinical chemistry or histopathology, an additional assessment factor of 3 for database quality is used for DNEL derivation. This additional factor is considered to be adequately protective based on the demonstrated low toxicity of related substances, components and metabolites of CAPA 3050.

Inhalation DNELs

For the general population, the starting point of 1000 mg/kg bw/d from an oral rat study is corrected for breathing volume (/1.15), and for the relative extent of oral and inhalation absorption (*0.5) to give a corrected (inhalation) starting point of 435 mg/m3.

 

Systemic inhalation DNELs 

Assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure: extrapolation from sub-acute to chronic duration), 4 for allometric scaling, 2.5 (for interspecies differences), 10 (for intraspecies differences), 3 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 450.  Application of the overall assessment factor to the corrected starting point gives a long-term systemic inhalation DNEL of 1.0 mg/m3 for the general population. CAPA 3050 is not classified for acute toxicity. In the absence of any acute hazard, an acute systemic inhalation DNEL is not derived.

 

Local inhalation DNELs 

CAPA 3050 is not an irritant or sensitiser. In the absence of any identified hazard, local inhalation DNEL values are not derived.

 

Dermal DNELs 

In the absence of information on the extent of oral and dermal absorption, these are considered to be equivalent. The corrected dermal starting point is therefore 100 mg/kg bw/d.

 

Systemic dermal DNELs 

Assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure: extrapolation from sub-acute to chronic duration), 2.5 (for interspecies differences), 10 (for intraspecies differences), 3 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 1800. Application of the overall assessment factor to the corrected starting point gives a long-term systemic dermal DNEL of 0.6 mg/kg bw/d for the general population. CAPA 3050 is not classified for acute toxicity. In the absence of any acute hazard, an acute systemic dermal DNEL is not derived.

 

Local dermal DNELs 

CAPA 3050 is not a skin irritant or sensitiser. In the absence of any identified hazard, local dermal DNEL values are not derived.

 

Oral DNELs 

Correction of the starting point is not required.

 

Systemic oral DNELs 

Assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure: extrapolation from sub-acute to chronic duration), 2.5 (for interspecies differences), 10 (for intraspecies differences), 3 (for database quality) and 1 (for remaining uncertainties) are combined to give an overall assessment factor of 1800. Application of the overall assessment factor to the corrected starting point gives a long-term systemic oral DNEL of 0.6 mg/kg bw/d for the general population. CAPA 3050 is not classified for acute toxicity. In the absence of any acute hazard, an acute systemic oral DNEL is not derived.