N,N,N',N'-tetramethyl-2,2'-oxybis(ethylamine)

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.16 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Dose descriptor starting point:

NOAEC

Value:

8.2 mg/m³

AF for dose response relationship:

1

Justification:

default assessment factor

AF for differences in duration of exposure:

2

Justification:

DNEL is based on 14 week inhalation study - sub-chronic to chronic AF of 2 is applied

AF for interspecies differences (allometric scaling):

1

Justification:

AF not used for inhalation route

AF for other interspecies differences:

2.5

Justification:

No data are available on any remaining interspecies uncertainties; therefore, the default factor of 2.5 was applied.

AF for intraspecies differences:

5

Justification:

Standard default for workers

AF for the quality of the whole database:

1

Justification:

default assessment factor

AF for remaining uncertainties:

1

Justification:

default assessment factor

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.08 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

15

Dose descriptor:

LOAEC

Value:

1.51 mg/m³

AF for dose response relationship:

3

Justification:

LOAEC

AF for differences in duration of exposure:

1

Justification:

Increasing the duration does not increase the severity as is the case for certain local effects in the respiratory tract. This is relevant when there is no substantial difference in the N(L)OAECs following acute and subacute exposure by inhalation. The effects can thus be considered concentration rather than dose-dependent (ECHA R8, pg 29).

AF for interspecies differences (allometric scaling):

1

Justification:

AF not used for local effects

AF for other interspecies differences:

1

Justification:

Since local effects are independent of the basal metabolic rate, allometric scaling should not be applied (allometric scaling factor of 1). For the remaining uncertainties in kinetic (at a smaller extent) and in dynamic (at a larger extent) interspecies differences, consideration of the mechanism of toxicity is crucial, e.g. if the effect is a simple destruction of membranes due to the physicochemical properties (e.g. pH) of the chemical concerned as opposed to a mechanism involving local metabolism (see pg 26 of R8). The mechanism of action for the test substance is corrosion which is a simple destruction of membranes.

AF for intraspecies differences:

5

Justification:

Standard default for workers

AF for the quality of the whole database:

1

Justification:

N/A

AF for remaining uncertainties:

1

Justification:

N/A

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:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

Long term exposure inhalation DNELs for systemic effects have been calculated for workers as 0.16 mg/m³. A long term inhalation DNEL for local effects was calculated as 0.08 mg/m³.

A DNEL could not be derived for dermal local effects as all doses tested produced local corrosivity effects. No systemic effects were observed at any of the doses tested. Therefore, in accordance with ECHA guidance, a qualitative assessment will be performed for long-term dermal effects.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.041 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Dose descriptor starting point:

NOAEC

Value:

8.2 mg/m³

Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation used

AF for dose response relationship:

1

Justification:

N/A

AF for differences in duration of exposure:

2

Justification:

DNEL is based on 14 week inhalation study - sub-chronic to chronic AF of 2 is applied

AF for interspecies differences (allometric scaling):

1

Justification:

AF for inhalation not used

AF for other interspecies differences:

2.5

Justification:

No data are available on any remaining interspecies uncertainties; therefore, the default factor of 2.5 was applied.

AF for intraspecies differences:

10

Justification:

Standard default for general population

AF for the quality of the whole database:

1

Justification:

N/A

AF for remaining uncertainties:

1

Justification:

N/A

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.013 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

30

Dose descriptor:

LOAEC

Value:

1.51 mg/m³

AF for dose response relationship:

3

Justification:

LOAEC used

AF for differences in duration of exposure:

1

Justification:

Increasing the duration does not increase the severity as is the case for certain local effects in the respiratory tract. This is relevant when there is no substantial difference in the N(L)OAECs following acute and subacute exposure by inhalation. The effects can thus be considered concentration rather than dose-dependent (ECHA R8, pg 29).

AF for interspecies differences (allometric scaling):

1

Justification:

AF for inhalation exposure not used

AF for other interspecies differences:

1

Justification:

Since local effects are independent of the basal metabolic rate, allometric scaling should not be applied (allometric scaling factor of 1). For the remaining uncertainties in kinetic (at a smaller extent) and in dynamic (at a larger extent) interspecies differences, consideration of the mechanism of toxicity is crucial, e.g. if the effect is a simple destruction of membranes due to the physicochemical properties (e.g. pH) of the chemical concerned as opposed to a mechanism involving local metabolism (see pg 26 of R8). The mechanism of action for the test substance is corrosion which is a simple destruction of membranes.

AF for intraspecies differences:

10

Justification:

Standard default for general population

AF for the quality of the whole database:

1

Justification:

N/A

AF for remaining uncertainties:

1

Justification:

N/A

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:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.047 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Dose descriptor starting point:

NOAEC

Value:

8.2 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

2.36 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

A systemic inhalation NOAEC of 8.2 mg/m3 was obtained in a 14-wk repeated dose study on rats. 100% absorption for the oral and the inhalative route for animals and humans is assumed. A conversion factor from 6 hours of exposure in the study to 24 hours for the general population (4) is applied. An inhalation to oral conversion factor of of 1.15 m3/kg bw is applied following REACH R.8 Example 8.1 to obtain a corrected NOAEL for the general population of: 8.2 mg/m3 *1.15 m3/kg bw / 4 = 2.36 mg/kg bw /d.

AF for dose response relationship:

1

Justification:

N/A

AF for differences in duration of exposure:

2

Justification:

DNEL is based on 14 week inhalation study - sub-chronic to chronic AF of 2 is applied

AF for interspecies differences (allometric scaling):

1

Justification:

N/A

AF for other interspecies differences:

2.5

Justification:

No data are available on any remaining interspecies uncertainties; therefore, the default factor of 2.5 was applied.

AF for intraspecies differences:

10

Justification:

Standard default for general population

AF for the quality of the whole database:

1

Justification:

N/A

AF for remaining uncertainties:

1

Justification:

N/A

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

Long term exposure inhalation DNELs for systemic effects have been calculated for the general population as 0.041 mg/m³. A long term inhalation DNEL for local effects was calculated as 0.013 mg/m³.

A long term oral DNEL of 0.047 mg/kg bw/day was determined. A systemic long term dermal DNEL could not be derived as all doses tested produced local corrosivity effects. Therefore, in accordance with ECHA guidance, a qualitative assessment will be performed for dermal exposure.