Amines, N-C16-22-alkyltrimethylenedi-

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.04 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):

25

Modified dose descriptor starting point:

NOAEC

Value:

0.99 mg/m³

Explanation for the modification of the dose descriptor starting point:

Starting point: NOAEL (oral route, subchronic) = 0.4 mg/kg bw/day
Correction factor for differences in respiratory volume (rat/workers): 1/0.38
Correction factor for light activity at work: 6.7/10
Correction factor for difference between human and experimental exposure conditions: 7/5 (In the study, animals were exposed 7 days per week, and workers work 5 days per week).
Absorptions by inhalation and oral route were concluded to be equivalent (100%).
NOAEC = NOAEL x (1/0.38) x (6.7/10) x 7/5 = 9.2 x (1/0.38) x (6.7/10) x 7/5 = 0.99 mg/m3

AF for dose response relationship:

1

Justification:

ECHA REACH Guidance

AF for differences in duration of exposure:

2

Justification:

Sub-chronic to chronic exposure

AF for interspecies differences (allometric scaling):

1

Justification:

ECHA REACH Guidance

AF for other interspecies differences:

2.5

Justification:

ECHA REACH Guidance

AF for intraspecies differences:

5

Justification:

ECHA REACH Guidance

AF for the quality of the whole database:

1

Justification:

ECHA REACH Guidance

AF for remaining uncertainties:

1

Justification:

ECHA REACH Guidance

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.006 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):

100

Modified dose descriptor starting point:

NOAEL

Value:

0.4 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Starting point: NOAEL (oral route, subacute) = 0.4 mg/kg bw/day

Absorptions by the dermal route was concluded to represent 100% of the absorption following exposure via the oral route.

Correction factor for difference between human and experimental exposure conditions: 7/5 (In the study, animals were exposed 7 days per week, and workers work 5 days per week).

NOAEL = NOAEL x 7/5 = 0.4 x 7/5 = 0.56 mg/kg bw/d

AF for dose response relationship:

1

Justification:

ECHA REACH Guidance

AF for differences in duration of exposure:

2

Justification:

Sub-chronic to chronic exposure

AF for interspecies differences (allometric scaling):

4

Justification:

Rat to human.

AF for other interspecies differences:

2.5

Justification:

ECHA REACH Guidance

AF for intraspecies differences:

5

Justification:

ECHA REACH Guidance

AF for the quality of the whole database:

1

Justification:

ECHA REACH Guidance

AF for remaining uncertainties:

1

Justification:

ECHA REACH Guidance

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)

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)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.007 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:

0.35 mg/m³

Explanation for the modification of the dose descriptor starting point:

Starting point: NOAEL (oral route, subchronic) = 0.4 mg/kg bw/day

Correction factor for differences in respiratory volume (rat/general population): 1/1.15

Absorptions by inhalation and oral route were concluded to be equivalent (100%).

NOAEC = NOAEL x (1/1.15) = 0.4 x (1/1.15) = 0.35 mg/m3

AF for dose response relationship:

1

Justification:

ECHA REACH Guidance

AF for differences in duration of exposure:

2

Justification:

Sub-chronic to chronic exposure

AF for interspecies differences (allometric scaling):

1

Justification:

ECHA REACH Guidance

AF for other interspecies differences:

2.5

Justification:

ECHA REACH Guidance

AF for intraspecies differences:

10

Justification:

ECHA REACH Guidance

AF for the quality of the whole database:

1

Justification:

ECHA REACH Guidance

AF for remaining uncertainties:

1

Justification:

ECHA REACH Guidance

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.002 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):

200

Modified dose descriptor starting point:

NOAEL

Value:

0.4 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL from 90-day study on C12-14-Diamine: 0.4 mg/kgbw/d At this stage no data are available on dermal absorption. Diamines are not expected to easily pass the skin in view of its ionised form at physiological conditions. However, as this is not quantitatively evaluated, 100% dermal absorption is considered as worst case assumption.

AF for dose response relationship:

1

Justification:

ECHA REACH Guidance

AF for differences in duration of exposure:

2

Justification:

Sub-chronic to chronic exposure

AF for interspecies differences (allometric scaling):

4

Justification:

Rat to human.

AF for other interspecies differences:

2.5

Justification:

ECHA REACH Guidance

AF for intraspecies differences:

10

Justification:

ECHA REACH Guidance

AF for the quality of the whole database:

1

Justification:

ECHA REACH Guidance

AF for remaining uncertainties:

1

Justification:

ECHA REACH Guidance

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:

0.002 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):

200

Dose descriptor starting point:

NOAEL

Value:

0.4 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No modification of the dose descriptor starting point is required.

AF for dose response relationship:

1

Justification:

ECHA REACH Guidance

AF for differences in duration of exposure:

2

Justification:

Sub-chronic to chronic exposure

AF for interspecies differences (allometric scaling):

4

Justification:

Rat to human.

AF for other interspecies differences:

2.5

Justification:

ECHA REACH Guidance

AF for intraspecies differences:

10

Justification:

ECHA REACH Guidance

AF for the quality of the whole database:

1

Justification:

ECHA REACH Guidance

AF for remaining uncertainties:

1

Justification:

ECHA REACH Guidance

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

No exposure of the general population to Amines, N-C16-22-alkyltrimethylenedi- based on the uses indicated in this dossier that are limited to industrial manufacture and formulation.

However, to allow for evaluation from indirect exposures via the environment, DNELs have been derived for systemic toxicity from long term exposures via all routes.