Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, N-(hydroxyethyl) derivs.

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.12 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):

6

Modified dose descriptor starting point:

NOAEC

Value:

0.705 mg/m³

Explanation for the modification of the dose descriptor starting point:

Starting point cross-reading NOAEL 90-day on C12-14-Diamine: 0.4 mg/kgbw/d (justification see section 7.5 repeated dose and document in support of cross-reading) The corrected 8 hr inhalation NOAEC for workers is NOAEL(0.4 mg/kg) * 1.76 mg/m3 = 0.705 mg/m3. No factor 2 route extrapolation from oral to inhalation is applied: Due to very low vp (< 0.0015 Pa), exposure is only possible as aerosol. If any inhalation does occur, this can only be in the form of larger droplets, as the use does not include fine spraying. Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This results to no principal difference in absorption compared oral route.

AF for dose response relationship:

1

Justification:

No specific concerns; starting point is NOAEL, effects at LOAEL are not severe and of local nature.

AF for differences in duration of exposure:

2

Justification:

Default assessment factor for sub-chronic to chronic. However, we know that the dose levels of the NOAEL for this effect of foamy macrophages in mesenteric lymph nodes is not influenced by the duration of the study.

AF for interspecies differences (allometric scaling):

1

Justification:

Already included in NOAEC calculation

AF for other interspecies differences:

1

Justification:

ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied. As effects are interpreted as being local and related to the route of exposure (see comments), the already applied allometric scaling already represents a worst case.

AF for intraspecies differences:

3

Justification:

ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intra-species differences for workers is 3 and not 5. As the effects for which the risk assessment is made is based on a local response following an non-specific mechanism with expected inherently relative low variation between individuals, no additional factor is needed to accommodate for possible high uncertainty between individuals on the basis of possible specific sensitivities.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results within category.

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

repeated dose toxicity

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:

0.017 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):

24

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 cross-reading NOAEL 90-day on C12-14-Diamine: 0.4 mg/kgbw/d (justification see section 7.5 repeated dose and document in support of cross-reading). At this stage no data are available on dermal absorption. Diamines  and  diamine ethoxylated are not expected to easily pass the skin. However, as this is not quantitatively evaluated, 100% dermal absorption is considered as worst case assumption.

AF for dose response relationship:

1

Justification:

No specific concerns. Effects at LOAEL are not severe and probably only of local nature.

AF for differences in duration of exposure:

2

Justification:

Default assessment factor for sub-chronic to chronic. However, we know that the dose levels of the NOAEL for this effect of foamy macrophages in mesenteric lymph nodes is not influenced by the duration of the study.

AF for interspecies differences (allometric scaling):

4

Justification:

Default factor for allometric scaling from rat to human.

AF for other interspecies differences:

1

Justification:

ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied. As effects are interpreted as being local related to the route of exposure, the applied allometric scaling already represents a worst case.

AF for intraspecies differences:

3

Justification:

ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intra-species differences for workers is 3 and not 5. As the effects for which the risk assessment is made is based on a local response following an non-specific mechanism with expected inherently relative low variation between individuals, no additional factor is needed to accommodate for possible high uncertainty between individuals on the basis of possible specific sensitivities.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results within category.

AF for remaining uncertainties:

1

Justification:

Cross-reading to more extended studies on non-ethoxylated amines does also not indicate additional concerns to be considered.

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)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.025 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):

14

Modified dose descriptor starting point:

NOAEC

Value:

0.35 mg/m³

Explanation for the modification of the dose descriptor starting point:

Starting point cross-reading NOAEL 90-day on C12-14-Diamine: 0.4 mg/kgbw/d (justification see section 7.5 repeated dose and document in support of cross-reading) The corrected 24 hr inhalation NOAEC for general population is NOAEL(0.4 mg/kg) * 1/1.15 mg/m3 = 0.35 mg/m3. No factor 2 route extrapolation from oral to inhalation. Due to very low vp (< 0.0015 Pa), exposure is only possible as aerosol or larger particles. If any inhalation does occur, this can only be in the form of larger droplets, as the use does not include fine spraying. Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This results to no principal difference in absorption compared oral route. Besides, absorption is considered to be 100% both via oral and inhalation route.

AF for dose response relationship:

1

Justification:

No specific concerns; effects at LOAEL are not severe and of local nature.

AF for differences in duration of exposure:

2

Justification:

Default assessment factor for sub-chronic to chronic. However, we know that the dose levels of the NOAEL for this effect of foamy macrophages in mesenteric lymph nodes is not influenced by the duration of the study.

AF for interspecies differences (allometric scaling):

1

Justification:

Already included in NOAEC calculation

AF for other interspecies differences:

1

Justification:

ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied. As effects are interpreted as being local and related to the route of exposure (see comments), the already applied allometric scaling already represents a worst case.

AF for intraspecies differences:

7

Justification:

ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intraspecies differences for general public is 5 and not 10, In this case the factor 7 is used to accommodate for the possible high uncertainty between individuals as the effects for which the risk assessment is made possibly includes a local response.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results within category.

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

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

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.007 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):

56

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 cross-reading NOAEL 90-day on C12-14-Diamine: 0.4 mg/kgbw/d (justification see section 7.5 repeated dose and document in support of cross-reading). At this stage no data are available on dermal absorption. Diamines  and  diamine ethoxylated are not expected to easily pass the skin. However, as this is not quantitatively evaluated, 100% dermal absorption is considered as worst case assumption.

AF for dose response relationship:

1

Justification:

No specific concerns. Effects at LOAEL are not severe and probably only of local nature.

AF for differences in duration of exposure:

2

Justification:

Default assessment factor for sub-chronic to chronic. However, we know that the dose levels of the NOAEL for this effect of foamy macrophages in mesenteric lymph nodes is not influenced by the duration of the study.

AF for interspecies differences (allometric scaling):

4

Justification:

Default factor for allometric scaling from rat to human.

AF for other interspecies differences:

1

Justification:

ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied. As effects are interpreted as being local related to the route of exposure, the applied allometric scaling already represents a worst case.

AF for intraspecies differences:

7

Justification:

ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intraspecies differences for general public is 5 and not 10, In this case the factor 7 is used to accommodate for the possible high uncertainty between individuals as the effects for which the risk assessment is made possibly includes a local response.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results within category.

AF for remaining uncertainties:

1

Justification:

Cross-reading to more extended studies on non-ethoxylated amines does also not indicate additional concerns to be considered.

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

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.007 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):

56

Modified dose descriptor starting point:

NOAEL

Value:

0.4 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Not applicable as studie was performed by oral route

AF for dose response relationship:

1

Justification:

No specific concerns; effects at LOAEL are not severe and of local nature.

AF for differences in duration of exposure:

2

Justification:

Default assessment factor for sub-chronic to chronic. However, we know that the dose levels of the NOAEL for this effect of foamy macrophages in mesenteric lymph nodes is not influenced by the duration of the study.

AF for interspecies differences (allometric scaling):

4

Justification:

Default factor for allometric scaling from rat to human.

AF for other interspecies differences:

1

Justification:

ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied. As effects are interpreted as being local related to the route of exposure, the applied allometric scaling already represents a worst case.

AF for intraspecies differences:

7

Justification:

ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intraspecies differences for general public is 5 and not 10, In this case the factor 7 is used to accommodate for the possible high uncertainty between individuals as the effects for which the risk assessment is made possibly includes a local response.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results within category.

AF for remaining uncertainties:

1

Justification:

Cross-reading to more extended studies on non-ethoxylated amines does also not indicate additional concerns to be considered.

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

The uses indicated in this dossier are limited to industrial and professional users and exposure of the general population to Tallow-diamine3EO is not to be expected.
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.