Undecan-4-olide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

19 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

Modified dose descriptor starting point:

NOAEC

Value:

1 423 mg/m³

Explanation for the modification of the dose descriptor starting point:

For potential inhalation exposure, route-to-route extrapolation from the oral NOAEL value (1000 mg/kg bw/d) of gamma-caprolactone (aliphatic lactone used in a read-across approach) was performed. In the absence of specific data for both the starting route (oral) and the end route (inhalation), worst case assumptions have to be made. It was assumed that a limited absorption occurs by the oral route, leading to a low (conservative) internal NOAEL. To secure a conservative external NOAEL, a maximum absorption should be assumed for the inhalation route (i.e.; 100%) leading to a low external NOAEL. Thus, in the case of oral-to- inhalation extrapolation, it is proposed to include a default factor of 2, i.e. the absorption percentage by oral route is half that of the inhalation absorption as suggested on page 19 of Guidance Document, Chapter R.8. Finally, to convert the oral NOAEL into inhalatory NOAEC, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 0.38 m3/kg bw/8 h). For workers a correction was added for the difference between respiratory rates under standard conditions (sRVhuman: 6.7 m3 for an 8-h exposure period) and under conditions of light activity (wRV: 10 m3 for an 8-h exposure period). Thus, for gamma-caprolactone, the corrected dose descriptor for inhalation is 882 mg/m3 for workers. Then, a correction factor based on the ratio between the molecular mass of gamma-undecalactone (184 g/ml) and gamma-caprolactone (114 g/mol) was applied to extrapolate the corrected starting point for gamma-undecalactone.

AF for dose response relationship:

1

AF for differences in duration of exposure:

6

Justification:

Subacute to chronic extrapolation as DNEL is based on 28-day study

AF for interspecies differences (allometric scaling):

1

Justification:

AF not used for inhalation route

AF for other interspecies differences:

2.5

Justification:

Remaining differences

AF for intraspecies differences:

5

Justification:

Worker

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

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:

5.38 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

Modified dose descriptor starting point:

NOAEL

Value:

1 614 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

For potential dermal exposure, route-to-route extrapolation from the oral NOAEL value was performed. In the absence of specific data and on the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor should be introduced when performing oral to dermal extrapolation (see Guidance Document, Chapter R.8, pp 19). Thus, for gamma-Caprolactone, the corrected dose descriptor for dermal route is 1000 mg/kg bw/day for workers. Then, a correction factor based on the ratio between the molecular mass of gamma-undecalactone (184 g/ml) and gamma-caprolactone (114 g/mol) was applied to extrapolate the corrected starting point for gamma-undecalactone.

AF for dose response relationship:

1

AF for differences in duration of exposure:

6

Justification:

Subacute to chronic extrapolation as DNEL is based on 28-day study

AF for interspecies differences (allometric scaling):

4

Justification:

Rat

AF for other interspecies differences:

2.5

Justification:

Remaining differences

AF for intraspecies differences:

5

Justification:

Worker

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.68 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

Modified dose descriptor starting point:

NOAEC

Value:

702 mg/m³

Explanation for the modification of the dose descriptor starting point:

For potential inhalation exposure, route-to-route extrapolation from the oral NOAEL value was performed. In the absence of specific data for both the starting route (oral) and the end route (inhalation), worst case assumptions have to be made. It was assumed that a limited absorption occurs by the oral route, leading to a low (conservative) internal NOAEL. To secure a conservative external NOAEL a maximum absorption should be assumed for the inhalation route (i.e.; 100%) leading to a low external NOAEL. Thus, in the case of oral-to- inhalation extrapolation, it is proposed to include a default factor of 2, i.e. the absorption percentage by oral route is half that of the inhalation absorption as suggested on page 19 of Guidance Document, Chapter R.8. Finally, to convert the oral NOAEL into inhalatory NOAEC, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 1.15 m3/kg bw/24 h). Thus, for gamma-caprolactone, the corrected dose descriptor for inhalation is 435 mg/m3 for the general population. Then, a correction factor based on the ratio between the molecular mass of gamma-undecalactone (184 g/ml) and gamma-caprolactone (114 g/mol) was applied to extrapolate the corrected starting point for gamma-undecalactone.

AF for dose response relationship:

1

Justification:

NOAEL

AF for differences in duration of exposure:

6

Justification:

Subacute to chronic extrapolation as DNEL is based on 28-day study

AF for interspecies differences (allometric scaling):

1

Justification:

AF not used for inhalation route

AF for other interspecies differences:

2.5

Justification:

Remaining differences

AF for intraspecies differences:

10

Justification:

General population

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

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:

2.7 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

Modified dose descriptor starting point:

NOAEL

Value:

1 614 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

For potential dermal exposure, route-to-route extrapolation from the oral NOAEL value was performed. In the absence of specific data and on the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor should be introduced when performing oral to dermal extrapolation (see Guidance Document, Chapter R.8, pp 19). Thus, for gamma-caprolactone, the corrected dose descriptor for dermal route is 1000 mg/kg bw/day for the general population. Then, a correction factor based on the ratio between the molecular mass of gamma-undecalactone (184 g/ml) and gamma-caprolactone (114 g/mol) was applied to extrapolate the corrected starting point for gamma-undecalactone.

AF for dose response relationship:

1

Justification:

NOAEL

AF for differences in duration of exposure:

6

Justification:

Subacute to chronic extrapolation as DNEL is based on 28-day study

AF for interspecies differences (allometric scaling):

4

Justification:

Rat

AF for other interspecies differences:

2.5

Justification:

Remaining differences

AF for intraspecies differences:

10

Justification:

General population

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

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:

2.7 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

Modified dose descriptor starting point:

NOAEL

Value:

1 614 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The oral NOAEL value was used as the dose descriptor for DNEL long-term for oral route derivation. However, a correction factor based on the ratio between the molecular mass of gamma-undecalactone (184 g/ml) and gamma-caprolactone (114 g/mol) was applied to extrapolate the corrected starting point for gamma-undecalactone.

AF for dose response relationship:

1

Justification:

NOAEL

AF for differences in duration of exposure:

6

Justification:

Subacute to chronic extrapolation as DNEL is based on 28-day study

AF for interspecies differences (allometric scaling):

4

Justification:

Rat

AF for other interspecies differences:

2.5

Justification:

Remaining differences

AF for intraspecies differences:

10

Justification:

General population

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

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