ε-Caprolactone, oligomeric reaction products with 2,2'-oxydiethanol

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

12 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:

882 mg/m³

Explanation for the modification of the dose descriptor starting point:

The relevant starting point is the NOAEL of 1000 mg/kg bw/d from the OECD 422 screening study with ε-caprolactone, oligomeric reaction products with 2,2'-oxydiethanol.  A corrected starting point (inhalation NOAEC) of 882 mg/m3 can be calculated based on activity (*6.7/10) and breathing rate (*1/0.38), and for the relative extent of oral (50%) and inhalation absorption (100%).  

AF for dose response relationship:

1

Justification:

The default ECHA assessment factor is appropriate as the starting point is derived from a NOAEL.

AF for differences in duration of exposure:

6

Justification:

The ECHA assessment factor of 6 is used to take into account extrapolation from a sub-acute study to chronic exposure.

AF for interspecies differences (allometric scaling):

1

Justification:

An assessment factor covering allometric factors is not required as these are taken into account when deriving the corrected (inhalation) starting point.

AF for other interspecies differences:

2.5

Justification:

The default ECHA assessment factor is appropriate to cover interspecies differences

AF for intraspecies differences:

5

Justification:

The ECHA assessment factor of 5 is appropriate to cover intraspecies differences (workers)

AF for the quality of the whole database:

1

Justification:

An addtional assessment factor is not required as the database is of high quality.

AF for remaining uncertainties:

1

Justification:

An additional assessment factor is not required 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 relevant starting point is the NOAEL of 1000 mg/kg bw/d from the screening study with ε-caprolactone, ologimeric reaction products with 2,2'-oxydiethanol.  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 1000 mg/kg bw/d is therefore calculated.

AF for dose response relationship:

1

Justification:

The default ECHA assessment factor is appropriate as the starting point is derived from a NOAEL.

AF for differences in duration of exposure:

6

Justification:

The ECHA assessment factor of 6 is used to take into account extrapolation from a sub-acute study to chronic exposure.

AF for interspecies differences (allometric scaling):

4

Justification:

The ECHA assessment factor of 4 is used as the starting point is derived from a study in the rat

AF for other interspecies differences:

2.5

Justification:

The default ECHA assessment factor is appropriate to cover interspecies differences

AF for intraspecies differences:

5

Justification:

The ECHA assessment factor of 5 is appropriate to cover intraspecies differences (workers)

AF for the quality of the whole database:

1

Justification:

An addtional assessment factor is not required as the database is of high quality.

AF for remaining uncertainties:

1

Justification:

An additional assessment factor is not required 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 substance (ϵ-caprolactone, oligomeric reaction products with 2,2’-oxydiethanol) is of low acute oral toxicity and is assumed also to be of low acute dermal toxicity. No acute inhalation toxicity are available; however inhalation is not considered to be a primary route of exposure based on the uses and physicochemical properties of the substance. The substance is not a skin irritant, eye irritant and is not mutagenic in studies in vitro. The substance is also of low repeated dose toxicity and there is no evidence of reproductive or developmental toxicity from an OECD 422 screening study. A NOAEL of 1000 mg/kg bw/d for the screening study (sub-acute, oral) is used as the starting point for DNEL derivation.

Inhalation DNELs

The relevant starting point is the NOAEL of 1000 mg/kg bw/d from the OECD 422 screening study with ε-caprolactone, oligomeric reaction products with 2,2'-oxydiethanol.  A corrected starting point (inhalation NOAEC) of 882 mg/m3 can be calculated based on activity (*6.7/10) and breathing rate (*1/0.38), and for the relative extent of oral (50%) and inhalation absorption (100%).  Individual assessment factors of 1 (for dose-response relationship), 6 (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 75.  Application of the overall assessment factor to the corrected starting point results in a long-term systemic inhalation DNEL of 12 mg/m3.

The substance is of low acute oral toxicity and is not classified for acute toxicity. In the absence of any identified hazard, a short-term systemic inhalation DNEL is not proposed.

No data on inhalation exposure are available; however the substance is not a skin irritant or eye irritant and respiratory irritation is not predicted. In the absence of any identified hazard, local inhalation DNELs are not proposed.

Dermal DNELs

The relevant starting point is the NOAEL of 1000 mg/kg bw/d from the screening study with caprolactone, oligomeric reaction products with 2,2'-oxydiethanol. 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 1000 mg/kg bw/d is therefore calculated. Individual assessment factors of 1 (for dose-response relationship), 6 (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 300. Application of the overall assessment factor to the corrected starting point results in a long-term systemic dermal DNEL of 3.3 mg/kg bw/d.

The substance is of low acute oral toxicity and is not classified for acute toxicity. Low acute dermal toxicity is also assumed. In the absence of any identified hazard, a short-term systemic dermal DNEL is not proposed.

The substance is not classified as a skin irritant or skin sensitiser. In the absence of any identified hazard, local dermal DNELs are not proposed.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

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):

150

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:

The relevant starting point is the NOAEL of 1000 mg/kg bw/d from the screening study with ε-caprolactone, oligoneric reaction products with 2,2'-oxydiethanol.  A corrected starting point (inhalation NOAEC) of 435 mg/m3 can be calculated based on breathing rate (*1/1.15) and for the relative extent of oral (50%) and inhalation absorption (100%).  

AF for dose response relationship:

1

Justification:

The default ECHA assessment factor is appropriate as the starting point is derived from a NOAEL

AF for differences in duration of exposure:

6

Justification:

The ECHA assessment factor of 6 is used to take into account extrapolation from a sub-acute study to chronic exposure

AF for interspecies differences (allometric scaling):

1

Justification:

The ECHA assessment factor of 6 is used to take into account extrapolation from a sub-acute study to chronic exposure

AF for other interspecies differences:

2.5

Justification:

The default ECHA assessment factor is appropriate to cover interspecies differences

AF for intraspecies differences:

10

Justification:

The ECHA assessment factor of 10 is appropriate to cover intraspecies differences (general population)

AF for the quality of the whole database:

1

Justification:

An addtional assessment factor is not required as the database is of high quality.

AF for remaining uncertainties:

1

Justification:

An additional assessment factor is not required 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 relevant starting point is the NOAEL of 1000 mg/kg bw/d from the screening study with ϵ-caprolactone, oligomeric reaction products with 2,2’-oxydiethanol. 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 1000 mg/kg bw/d is therefore calculated.

AF for dose response relationship:

1

Justification:

The default ECHA assessment factor is appropriate as the starting point is derived from a NOAEL.

AF for differences in duration of exposure:

6

Justification:

The ECHA assessment factor of 6 is used to take into account extrapolation from a sub-acute study to chronic exposure.

AF for interspecies differences (allometric scaling):

4

Justification:

The ECHA assessment factor of 4 is used as the starting point is derived from a study in the rat

AF for other interspecies differences:

2.5

Justification:

The default ECHA assessment factor of 2.5 is used to take into account interspecies differences

AF for intraspecies differences:

10

Justification:

The ECHA assessment factor of 10 is appropriate to cover intraspecies differences (general population)

AF for the quality of the whole database:

1

Justification:

An addtional assessment factor is not required as the database is of high quality.

AF for remaining uncertainties:

1

Justification:

An additional assessment factor is not required 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:

Modification of the starting point is not required as the NOAEL is derived from an oral study.

AF for dose response relationship:

1

Justification:

The default ECHA assessment factor is appropriate as the starting point is derived from a NOAEL.

AF for differences in duration of exposure:

6

Justification:

The ECHA assessment factor of 6 is used to take into account extrapolation from a sub-acute study to chronic exposure.

AF for interspecies differences (allometric scaling):

4

Justification:

The ECHA assessment factor of 4 is used as the starting point is derived from a study in the rat

AF for other interspecies differences:

2.5

Justification:

The default ECHA assessment factor of 2.5 is used to account for other interspecies differences

AF for intraspecies differences:

10

Justification:

The ECHA assessment factor of 10 is appropriate to cover intraspecies differences (general population)

AF for the quality of the whole database:

1

Justification:

An addtional assessment factor is not required as the database is of high quality.

AF for remaining uncertainties:

1

Justification:

An additional assessment factor is not required 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 substance ϵ-caprolactone, oligomeric reaction products with 2,2’-oxydiethanol is of low acute oral toxicity and is assumed also to be of low acute dermal toxicity. No acute inhalation toxicity are available; however inhalation is not considered to be a primary route of exposure based on the uses and physicochemical properties of the substance. The substance is not a skin irritant, eye irritant and is not mutagenic in studies in vitro. The substance is also of low repeated dose toxicity and there is no evidence of reproductive or developmental toxicity from an OECD 422 screening study. A NOAEL of 1000 mg/kg bw/d for the screening study (sub-acute, oral) is used as the starting point for DNEL derivation.

Inhalation DNELs

The relevant starting point is the NOAEL of 1000 mg/kg bw/d from the screening study with ε-caprolactone, oligomeric reaction products with 2,2'-oxydiethanol. A corrected starting point (inhalation NOAEC) of 435 mg/m3 can be calculated based on breathing rate (*1/1.15) and for the relative extent of oral (50%) and inhalation absorption (100%). Individual assessment factors of 1 (for dose-response relationship), 6 (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 150. Application of the overall assessment factor to the corrected starting point results in a long-term systemic inhalation DNEL of 3 mg/m3

The substance is of low acute oral toxicity and is not classified for acute toxicity. In the absence of any identified hazard, a short-term systemic inhalation DNEL is not proposed.

No data on inhalation exposure are available; however the substance is not a skin irritant or eye irritant and respiratory irritation is not predicted. In the absence of any identified hazard, a local inhalation DNELs are not proposed.

Dermal DNELs

The relevant starting point is the NOAEL of 1000 mg/kg bw/d from the screening study with the substance. 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 1000 mg/kg bw/d is therefore calculated. Individual assessment factors of 1 (for dose-response relationship), 6 (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 600. Application of the overall assessment factor to the corrected starting point results in a long-term systemic dermal DNEL of 1.7 mg/kg bw/d.

The substance is of low acute oral toxicity and is not classified for acute toxicity. Low acute dermal toxicity is also assumed. In the absence of any identified hazard, a short-term systemic dermal DNEL is not proposed.

The substance is not classified as a skin irritant or skin sensitiser. In the absence of any identified hazard, a local dermal DNELs are not proposed.

Oral DNELs

Modification of the starting point is not required as the NOAEL is derived from an oral study. Individual assessment factors of 1 (for dose-response relationship), 6 (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 600. Application of the overall assessment factor to the corrected starting point results in a long-term systemic oral DNEL of 1.7 mg/kg bw/d.

The substance is of low acute oral toxicity and is not classified for acute toxicity. In the absence of any identified hazard, a short-term systemic oral DNEL is not proposed.