Fatty acids, C18-unsatd., reaction products with ammonia-ethanolamine reaction by-products

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.7 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance (with ECETOC modification)

Overall assessment factor (AF):

10

Modified dose descriptor starting point:

NOAEC

Value:

17.6 mg/m³

Explanation for the modification of the dose descriptor starting point:

An OECD 408 compliant 90-day study in rat via oral route with AAI-DETA resulted to an overall NOAEL of 10 mg/kg/day. The corrected 8 hr inhalation NOAEC for workers is NOAEL (10) * 1.76 mg/m3 = 17.6 mg/m3. No factor 2 for route extrapolation from oral to inhalation is applied: Due to very low vp (8.4x10-8 Pa at 25°C), exposure is only possible as aerosol. If any exposure via inhalation does occur, this can only be in the form of larger droplets, as the use does not include fine spraying or mists. Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This result to no principal difference in absorption compared to oral route.

AF for dose response relationship:

1

Justification:

No specific concerns. Effects at LOAEL are of local nature.

AF for differences in duration of exposure:

2

Justification:

The guidance indicates that for subchronic to chronic a factor 2 should be applied. A lower factor could be considered on the basis of the understanding 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. Additionally, the further applied intraspecies factor sufficiently includes the remaining differences factor for interspecies. As effects are interpreted as being local and related to the route of exposure, the already applied allometric scaling already represents a worst case.

AF for intraspecies differences:

5

Justification:

ECETOC reported in 2010 after an extensive scientific review that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intra-species variability, which includes the remaining differences factor of 2.5 for interspecies. This factor may be increased by modified factors as suggested by the German Auschuss für Gefahrstoffe leading to an assessment factor of 5 for workers. 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 are derived from recent, high quality and valid studies showing consistent results within category.

AF for remaining uncertainties:

1

Justification:

NOAEL of 10 mg/kg for systemic toxicity is conservative, considering that macrophages in the mesenteric lymph nodes are a local, porte d’entrée related effect due to the route of application, and not a systemic effect per se.

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.25 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 with ECETOC modification

Overall assessment factor (AF):

40

Modified dose descriptor starting point:

NOAEL

Value:

10 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

An OECD 408 compliant 90-day study in rat via oral route with AAI-DETA resulted to an overall NOAEL of 10 mg/kg/day. Extrapolation from oral NOAEL represents a worst case situation, as dermal absorption is considered to be lower compared to oral absorption.

AF for dose response relationship:

1

Justification:

No specific concerns. Effects at LOAEL are of local nature.

AF for differences in duration of exposure:

2

Justification:

The guidance indicates that for subchronic to chronic a factor 2 should be applied. A lower factor could be considered on the basis of the understanding 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. Additionally, the further applied intraspecies factor sufficiently includes the remaining differences factor for interspecies. As effects are interpreted as being local and related to the route of exposure, the already applied allometric scaling already represents a worst case.

AF for intraspecies differences:

5

Justification:

ECETOC reported in 2010 after an extensive scientific review that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intra-species variability, which includes the remaining differences factor of 2.5 for interspecies. This factor may be increased by modified factors as suggested by the German Auschuss für Gefahrstoffe leading to an assessment factor of 5 for workers. 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 are derived from recent, high quality and valid studies showing consistent results within category.

AF for remaining uncertainties:

1

Justification:

NOAEL of 10 mg/kg for systemic toxicity is conservative, considering that macrophages in the mesenteric lymph nodes are a local, porte d’entrée related effect due to the route of application, and not a systemic effect per se.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

low 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

Workers:

Inhalation route:

Use of the substance is limited to industrial and professional users. The likelihood of exposure via inhalation is low considering its high boiling point (> 300 °C) and very low vapour pressure (8.4x10^-8Pa at 25°C) and use applications that do not involve the forming of aerosols, particles or droplets of an inhalable size.

 

Dermal route:

No threshold effect: Substance is irritating to the skin, and corrosive to mucous membranes (eyes). Effects following dermal exposures will be characterized by local effects from irritation that are related to duration, quantity and concentration of the substance, rather than by systemic toxicity due to dermal uptake. Specifically considering that acute oral toxicity is low and dermal uptake is expected to be low.

For irritating/corrosive substances, the use of protective gloves and other equipment, such as face shields, aprons and good work practices are mandatory. As a result, direct dermal contact occurs only occasionally. Therefore, repeated substantial daily dermal exposure is unlikely. (For properly labelled corrosives, the emphasis in the CSR and ES should be on the presentation of adequate risk management measures, rather than on the assessment of the risks from dermal exposure.)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.6 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH guidance (with ECETOC modification)

Overall assessment factor (AF):

14

Modified dose descriptor starting point:

NOAEC

Value:

8.7 mg/m³

Explanation for the modification of the dose descriptor starting point:

An OECD 408 compliant 90-day study in rat via oral route with AAI-DETA resulted to an overall NOAEL of 10 mg/kg/day. The corrected 8 hr inhalation NOAEC for general population is NOAEL (10) * 1/1.15 mg/m3 = 8.7 mg/m3. No factor 2 for route extrapolation from oral to inhalation is applied: Due to very low vp (8.4x10-8 Pa at 25°C), exposure is only possible as aerosol. If any exposure via inhalation does occur, this can only be in the form of larger droplets, as the use does not include fine spraying or mists. Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This result to no principal difference in absorption compared to oral route.

AF for dose response relationship:

1

Justification:

No specific concerns. Effects at LOAEL are of local nature.

AF for differences in duration of exposure:

2

Justification:

The guidance indicates that for subchronic to chronic a factor 2 should be applied. A lower factor could be considered on the basis of the understanding 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. Additionally, the further applied intraspecies factor sufficiently includes the remaining differences factor for interspecies. As effects are interpreted as being local and related to the route of exposure, 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 assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intra-species variability, which includes the remaining differences factor of 2.5 for interspecies. This factor may be increased by modified factors as suggested by the German Auschuss für Gefahrstoffe leading to an assessment factor of 7 for general public. 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 are derived from recent, high quality and valid studies showing consistent results within category.

AF for remaining uncertainties:

1

Justification:

NOAEL of 10 mg/kg for systemic toxicity is conservative, considering that macrophages in the mesenteric lymph nodes are a local, porte d’entrée related effect due to the route of application, and not a systemic effect per se.

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:

0.18 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 (with ECETOC modification)

Overall assessment factor (AF):

56

Modified dose descriptor starting point:

NOAEL

Value:

10 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

An OECD 408 compliant 90-day study in rat via oral route with AAI-DETA resulted to an overall NOAEL of 10 mg/kg/day. Extrapolation from oral NOAEL represents a worst case situation, as dermal absorption is considered to be lower compared to oral absorption.

AF for dose response relationship:

1

Justification:

No specific concerns. Effects at LOAEL are of local nature.

AF for differences in duration of exposure:

2

Justification:

The guidance indicates that for subchronic to chronic a factor 2 should be applied. A lower factor could be considered on the basis of the understanding 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. Additionally, the further applied intraspecies factor sufficiently includes the remaining differences factor for interspecies. As effects are interpreted as being local and related to the route of exposure, 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 assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intra-species variability, which includes the remaining differences factor of 2.5 for interspecies. This factor may be increased by modified factors as suggested by the German Auschuss für Gefahrstoffe leading to an assessment factor of 7 for general public. 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 are derived from recent, high quality and valid studies showing consistent results within category.

AF for remaining uncertainties:

1

Justification:

NOAEL of 10 mg/kg for systemic toxicity is conservative, considering that macrophages in the mesenteric lymph nodes are a local, porte d’entrée related effect due to the route of application, and not a systemic effect per se.

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

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.18 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 (with ECETOC modification)

Overall assessment factor (AF):

56

Modified dose descriptor starting point:

NOAEL

Value:

10 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

An OECD 408 compliant 90-day study in rat via oral route with AAI-DETA resulted to an overall NOAEL of 10 mg/kg/day. As study is based on oral dosing, no route-to-route extrapolation is needed.

AF for dose response relationship:

1

Justification:

No specific concerns. Effects at LOAEL are of local nature.

AF for differences in duration of exposure:

2

Justification:

The guidance indicates that for subchronic to chronic a factor 2 should be applied. A lower factor could be considered on the basis of the understanding 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. Additionally, the further applied intraspecies factor sufficiently includes the remaining differences factor for interspecies. As effects are interpreted as being local and related to the route of exposure, 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 assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intra-species variability, which includes the remaining differences factor of 2.5 for interspecies. This factor may be increased by modified factors as suggested by the German Auschuss für Gefahrstoffe leading to an assessment factor of 7 for general public. 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 are derived from recent, high quality and valid studies showing consistent results within category.

AF for remaining uncertainties:

1

Justification:

NOAEL of 10 mg/kg for systemic toxicity is conservative, considering that macrophages in the mesenteric lymph nodes are a local, porte d’entrée related effect due to the route of application, and not a systemic effect per se.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

These substances are only applied in professional or industrial setting in oilfield and mining applications applying adequate PPE. Use results to the inclusion into or onto a matrix. Consequently, consumers/general population will not be exposed.

However, in order to be able to evaluate possible secondary exposures via environment, additionally long-term systemic DNELs for general population have been derived.