dodecane-12-lactam, manufacturing of, by-products from, distillation residues

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

17.63 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

Modified dose descriptor starting point:

NOAEC

Value:

881.6 mg/m³

Explanation for the modification of the dose descriptor starting point:

No inhalation study is available. According to ECHA Guidance – Chapter R8 (p25): “in the absence of route-specific information on the starting route, to include a default factor of 2 (i.e. the absorption percentage for the starting route is half that the end route) in the case of oral-to inhalation extrapolation”. Therefore, as no data is available on oral or inhalation absorption, the oral absorption is estimated to 50% and the inhalation absorption to 100%. The correction factor is 0.5 (50/100).

AF for dose response relationship:

1

AF for differences in duration of exposure:

4

Justification:

OECD 422 is 6 weeks exposure

AF for interspecies differences (allometric scaling):

1

AF for other interspecies differences:

2.5

Justification:

remaining differences

AF for intraspecies differences:

5

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

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

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

200

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

no extrapolation NOAEL DERMAL = NOAEL ORAL

AF for dose response relationship:

1

AF for differences in duration of exposure:

4

Justification:

OECD 422 Exposure 6 weeks.

AF for interspecies differences (allometric scaling):

4

AF for other interspecies differences:

2.5

AF for intraspecies differences:

5

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:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

2 Inhalation DNEL for long term systemic effects/Workers :

The relevant study to be selected for derivation of the DNEL is the OECD 422 combined repeated dose toxicity study with the reproduction test (2012).

Step 1) Relevant dose-descriptor:NOAEL, rat = 1000 mg/kg bw/d

Step 2) Modification of starting point:

The starting point was modified to get the correct starting point for DNEL derivation. As a first step, route-to-route extrapolation was performed as recommended in the "Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 26 f.:

The oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between the 8-hour standard inhalation volume of rats versus humans, for differences between oral absorption in rats and inhalative absorption in humans (50% and 100%, respectively), and for differences between the 8-hour inhalation volume of workers in rest versus workers in light activity, by multiplying with the corresponding factors (1000x 1/0.38 m³/kg/d x 50%/100% x 6.7 m³/10 m³).

The resulting corrected starting point for inhalation DNEL derivation for workers is equal to 881.6 mg/m³.

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

Step 3) Assessment factors:

* Interspecies: 2.5

* Intraspecies : 5(factor for workers)

* Exposure duration : 4 (subchronic to chronic exposure)

* Dose response: 1 (LOAEL > NOAEL)

* Quality of database: 1

AF total = 2.5x5x4x1x1 = 50

Step 4) DNEL calculation:

DNEL value = 881.6 / 50 = 17.61 mg/m3

DNEL Long-term Inhalation value for long term systemic effects in workers is 17.61 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.81 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):

100

Modified dose descriptor starting point:

NOAEC

Value:

881.6 mg/m³

Explanation for the modification of the dose descriptor starting point:

No inhalation study is available. According to ECHA Guidance – Chapter R8 (p25): “in the absence of route-specific information on the starting route, to include a default factor of 2 (i.e. the absorption percentage for the starting route is half that the end route) in the case of oral-to inhalation extrapolation”. Therefore, as no data is available on oral or inhalation absorption, the oral absorption is estimated to 50% and the inhalation absorption to 100%. The correction factor is 0.5 (50/100)

AF for dose response relationship:

1

AF for differences in duration of exposure:

4

AF for interspecies differences (allometric scaling):

1

AF for other interspecies differences:

2.5

AF for intraspecies differences:

10

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

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):

400

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The dermal absorption is 100% by default as no information is available of dermal absorption.

AF for dose response relationship:

1

AF for differences in duration of exposure:

4

AF for interspecies differences (allometric scaling):

4

AF for other interspecies differences:

2.5

AF for intraspecies differences:

10

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

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

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

None

AF for dose response relationship:

1

AF for differences in duration of exposure:

4

AF for interspecies differences (allometric scaling):

4

AF for other interspecies differences:

2.5

AF for intraspecies differences:

10

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)