3,3'-oxybis(ethyleneoxy)bis(propylamine)

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

59 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

18

Modified dose descriptor starting point:

NOAEC

Value:

1 058 mg/m³

Explanation for the modification of the dose descriptor starting point:

not applicable

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: sub-acute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is not applied, because the ventilation rate directly depends on the basal metabolic rate.

AF for other interspecies differences:

1

Justification:

There is no additional evidence for species differences including toxicodynamics. Therefore, no additional factor is used (ECETOC).

AF for intraspecies differences:

3

Justification:

The (ECETOC) default value for the relatively homogenous group "worker" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach of the DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

176 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):

3

DNEL extrapolated from long term DNEL

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

other: VCI (2010)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

13 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

other: based on Protective Action Criteria value (2012)

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.3 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

72

Modified dose descriptor starting point:

NOAEL

Value:

600 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

not applicable

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: sub-acute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric scaling is applied.

AF for other interspecies differences:

1

Justification:

There is no additional evidence for species differences including toxicodynamics. Therefore, no additional factor is used (ECETOC).

AF for intraspecies differences:

3

Justification:

The (ECETOC) default value for the relatively homogenous group "worker" is used.

AF for the quality of the whole database:

1

Justification:

The qualitiy of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach of the DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

The information related to acute/short-term and long-term exposure hazards via the different exposure routes has been already commented/discussed above. Additional discussion is presented below for acute/short-term and long-term inhalation exposure – local effects:

 

Due to the corrosive potential of 3,3’Oxybis(ethyleneoxy)bis(propylamine) respiratory irritation following inhalation exposure is likely. However, there are no substance specific data on respiratory irritation available.

 

If toxicity is determined by the corrosive properties of a substance (as it is in the present case) a generic threshold for respiratory irritation of 1 mg/m³ can be set even in the absence of experimental data (VCI, 2010). This threshold was used as DNEL(long term inhalation exposure, local effects).

 

With regard to local effects after acute/short term inhalation the PAC-1 value of 13 mg/m³ was used as DNEL. The PAC-1 value is the airborne concentration of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, nonsensory effects. However, these effects are not disabling and are transient and reversible upon cessation of exposure. Even though the PAC-1 value represents a concentration where still slight effects occur, it is justified to use it as DNEL(acute/short-term inhalation exposure, local effects) as workers represent a more homogeneous population group and peak exposure is limited to 15 min whereas the PAC-1 value covers exposures up to 60 min.

References:

VCI (Verband der Chemischen Industrie e.V.) (2010). Ableitung von DNEL für lokal reizende Stoffe mit guter Datenlage zur systemischen Toxizität, aber limitierter Datenlage zur Inhalationstoxizität. Published 21.01.2010.

PAC (Protective Action Criteria). Rev. 27, February 2012.http://www.atlintl.com/DOE/teels/teel.html

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

17 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

30

Modified dose descriptor starting point:

NOAEC

Value:

522 mg/m³

Explanation for the modification of the dose descriptor starting point:

not applicable

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: sub-acute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling is not applied, because the ventilation rate directly depends on the basal metabolic rate.

AF for other interspecies differences:

1

Justification:

There is no additional evidence for species differences including toxicodynamics (ECETOC). Therefore, no additional factor is used.

AF for intraspecies differences:

5

Justification:

The (ECETOC) default value for the relatively homogenous group "general population" is used.

AF for the quality of the whole database:

1

Justification:

The qualitiy of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach of the DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

52 mg/m³

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

3

DNEL extrapolated from long term DNEL

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.5 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

other: VCI (2010)

Overall assessment factor (AF):

2

AF for intraspecies differences:

2

Justification:

Extrapolation from worker to general population.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

6.5 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

other: based on Protective Action Criteria value (2012)

Overall assessment factor (AF):

2

Dose descriptor starting point:

other: PAC-1 value

AF for remaining uncertainties:

2

Justification:

The

General Population - 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

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

120

Modified dose descriptor starting point:

NOAEL

Value:

600 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

not applicable

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: sub-acute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric scaling is applied,

AF for other interspecies differences:

1

Justification:

There is no additional evidence for species differences including toxicodynamics (ECETOC). Therefore, no additional factor is used.

AF for intraspecies differences:

5

Justification:

The (ECETOC) default value for the relatively homogenous group "general population" is used.

AF for the quality of the whole database:

1

Justification:

The qualitiy of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach of the DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

General Population - Hazard via oral 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

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

120

Modified dose descriptor starting point:

NOAEL

Value:

600 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

not applicable

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: sub-acute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric scaling is applied,

AF for other interspecies differences:

1

Justification:

There is no additional evidence for species differences including toxicodynamics (ECETOC). Therefore, no additional factor is used.

AF for intraspecies differences:

5

Justification:

The (ECETOC) default value for the relatively homogenous group "general population" is used.

AF for the quality of the whole database:

1

Justification:

The qualitiy of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach of the DNEL derivation is conservative. No further assessment factors are required.

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)