Amides, C16-18 and C18-unsatd., N,N-bis(hydroxyethyl)

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

73.44 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):

18

Modified dose descriptor starting point:

NOAEC

Value:

1 322 mg/m³

Explanation for the modification of the dose descriptor starting point:

The relevant dose descriptor selected to derive the inhalation DNEL, was the subacute oral rat NOAEL of 750 mg/kg bw/day based on no treatment-related effects noted at any of the dose levels. This dose descriptor which is the starting point was corrected for route-to-route extrapolation [i.e., NOAELoral rat ÷ SRvrat x (SRvhuman ÷ WSRvhuman)] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’); where: NOAELoral rat = 750 mg/kg bw/d; SRvrat = 0.38 m3/kg bw; SRvhuman = 6.7 m3; WSRvhuman = 10 m3).

AF for dose response relationship:

1

Justification:

Dose-response (starting point is a NOAEL)

AF for differences in duration of exposure:

6

Justification:

Exposure duration (subcaute to chronic)

AF for interspecies differences (allometric scaling):

1

Justification:

No assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human) since this is already accounted for when obtaining the corrected NOEC

AF for other interspecies differences:

1

Justification:

Any remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used.

AF for intraspecies differences:

3

Justification:

Intraspecies variation (workers). ECETOC proposed in 2003, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.

AF for the quality of the whole database:

1

Justification:

Good quality

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:

4.16 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

12

Modified dose descriptor starting point:

NOAEL

Value:

50 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation applied

AF for dose response relationship:

1

Justification:

Dose-response (starting point is a NOAEL

AF for differences in duration of exposure:

1

Justification:

Exposure duration (chronic study)

AF for interspecies differences (allometric scaling):

4

Justification:

Assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)

AF for other interspecies differences:

1

Justification:

Any remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used.

AF for intraspecies differences:

3

Justification:

Intraspecies variation (workers). ECETOC proposed in 2003, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.

AF for the quality of the whole database:

1

Justification:

Good quality NTP study

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:

93.6 µg/cm²

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

3

Dose descriptor:

other: corrected LOAEL of 281 µg/cm²

AF for dose response relationship:

1

Justification:

Starting point is NOAEL

AF for differences in duration of exposure:

1

Justification:

Exposure duration (chronic study)

AF for interspecies differences (allometric scaling):

1

Justification:

Assessment factor for interspecies difference - allometric (metabolic rate) scaling (rat-to-human) not required since this is already accounted for when obtaining the corrected LOAEL

AF for other interspecies differences:

1

Justification:

Assessment factor for interspecies difference - remaining non-metabolic differences not required

AF for intraspecies differences:

3

Justification:

Intraspecies variation (workers). ECETOC proposed in 2003, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.

AF for the quality of the whole database:

1

Justification:

Good quality NTP conducted study

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

21.73 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):

30

Modified dose descriptor starting point:

NOAEC

Value:

652 mg/m³

Explanation for the modification of the dose descriptor starting point:

The relevant dose descriptor selected to derive the inhalation DNEL, was the subacute oral rat NOAEL of 750 mg/kg bw/day based on no treatment-related effects noted at any of the dose levels. This dose descriptor which is the starting point was corrected for route-to-route extrapolation [i.e., NOAELoral rat ÷ SRvrat] in accordance with REACH guidance document R.8 (‘Characterization of dose (concentration)-response for human health’); where: NOAELoral rat = 750 mg/kg bw/d; SRvrat = 1.15 m3/kg bw.

AF for dose response relationship:

1

Justification:

Dose-response (starting point is a NOEL)

AF for differences in duration of exposure:

6

Justification:

Exposure duration (subacute to chronic)

AF for interspecies differences (allometric scaling):

1

Justification:

No assessment factor applied for interspecies difference - allometric (metabolic rate) scaling (rat-to-human) since this is already accounted for when obtaining the corrected NOEC

AF for other interspecies differences:

1

Justification:

Any remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used.

AF for intraspecies differences:

5

Justification:

Intraspecies variation (general population). ECETOC proposed in 2003, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.

AF for the quality of the whole database:

1

Justification:

Good quality

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:

2.5 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

20

Modified dose descriptor starting point:

NOAEL

Value:

50 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation applied

AF for dose response relationship:

1

Justification:

Dose-response (starting point is a NOAEL)

AF for differences in duration of exposure:

1

Justification:

Exposure duration (chronic study)

AF for interspecies differences (allometric scaling):

4

Justification:

Assessment factor for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)

AF for other interspecies differences:

1

Justification:

Any remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used.

AF for intraspecies differences:

5

Justification:

Intraspecies variation (general population). ECETOC proposed in 2003, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.

AF for the quality of the whole database:

1

Justification:

Good quality

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:

56.2 µg/cm²

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

5

Dose descriptor:

other: corrected LOAEL of 281 µg/cm²

AF for dose response relationship:

1

Justification:

Starting point is NOAEL

AF for differences in duration of exposure:

1

Justification:

Exposure duration (chronic study)

AF for interspecies differences (allometric scaling):

1

Justification:

Assessment factor for interspecies difference - allometric (metabolic rate) scaling (rat-to-human) not required

AF for other interspecies differences:

1

Justification:

Assessment factor for interspecies difference - remaining non-metabolic differences not required

AF for intraspecies differences:

5

Justification:

Intraspecies variation (general population). ECETOC proposed in 2003, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.

AF for the quality of the whole database:

1

Justification:

Good quality NTP study

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:

6.25 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):

120

Modified dose descriptor starting point:

NOAEL

Value:

750 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation

AF for dose response relationship:

1

Justification:

Dose-response (starting point is a NOAEL)

AF for differences in duration of exposure:

6

Justification:

Exposure duration (sub-acute to chronic study)

AF for interspecies differences (allometric scaling):

4

Justification:

Assessment factor for interspecies difference - allometric (metabolic rate) scaling (rat-to-human)

AF for other interspecies differences:

1

Justification:

Any remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used.

AF for intraspecies differences:

5

Justification:

Intraspecies variation (general population). ECETOC proposed in 2003, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5.

AF for the quality of the whole database:

1

Justification:

Good quality study

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)