Amides, from C18-unsatd. fatty acids and polyethylenepolyamines

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10 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:

176 mg/m³

Explanation for the modification of the dose descriptor starting point:

A 28-day study with AAI-PolyEA Amide resulted to an overall NOAEL of 100 mg/kg/day. The corrected 8 hr inhalation NOAEC for workers is NOAEL (100) * 1.76 mg/m3 = 176 mg/m3. No factor 2 route extrapolation from oral to inhalation is applied. Due to very low vp (< 0.00017 mPa at 25°C), 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.

AF for differences in duration of exposure:

6

Justification:

The guidance indicates that for subacute to chronic a factor 6 should be applied.

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

Justification:

NOAEL of 100 mg/kg is possibly conservative. The NOAEL in based on an increased level of ALAT and ASAT at 300 mg/kg, without any morphological changes seen at histopathology, and that recovered to normal levels in the recovery period. It can be discussed whether the 300 mg/kg dose should be regarded as NOAEL level for this study.

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:

1.4 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

72

Modified dose descriptor starting point:

NOAEL

Value:

100 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

A 28-day study with AAI-PolyEA Amide resulted to an overall NOAEL of 100 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 not severe.

AF for differences in duration of exposure:

6

Justification:

The guidance indicates that for subacute to chronic a factor 6 should be applied.

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:

NOAEL of 100 mg/kg is possibly conservative. The NOAEL in based on an increased level of ALAT and ASAT at 300 mg/kg, without any morphological changes seen at histopathology, and that recovered to normal levels in the recovery period. It can be discussed whether the 300 mg/kg dose should be regarded as NOAEL level for this study.

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:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

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 (< 0.00017 mPa 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 corrosive and sensitising. Effects following dermal exposures will be characterized by local corrosive and possible sensitising effects that are related to duration, quantity and concentration of the substance, rather than by systemic toxicity due to dermal uptake. Specifically as acute oral toxicity is low.

For corrosive and sensitising 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:

2.9 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:

87 mg/m³

Explanation for the modification of the dose descriptor starting point:

A 28-day study with AAI-PolyEA Amide resulted to an overall NOAEL of 100 mg/kg/day. The corrected 24 hr inhalation NOAEC for general population is NOAEL (100) * 1/1.15 mg/m3 = 87 mg/m3. No factor 2 route extrapolation from oral to inhalation. Due to very low vp (< 0.00017 mPa at 25°C), 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. Effects at LOAEL are not severe.

AF for differences in duration of exposure:

6

Justification:

The guidance indicates that for subacute to chronic a factor 6 should be applied.

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:

5

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. 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:

NOAEL of 100 mg/kg is possibly conservative. The NOAEL in based on an increased level of ALAT and ASAT at 300 mg/kg, without any morphological changes seen at histopathology, and that recovered to normal levels in the recovery period. It can be discussed whether the 300 mg/kg dose should be regarded as NOAEL level for this study.

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)

Most sensitive endpoint:

skin irritation/corrosion

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:

0.83 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:

100 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

A 28-day study with AAI-PolyEA Amide resulted to an overall NOAEL of 100 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 not severe.

AF for differences in duration of exposure:

6

Justification:

The guidance indicates that for subacute to chronic a factor 6 should be applied.

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:

5

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. 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:

NOAEL of 100 mg/kg is possibly conservative. The NOAEL in based on an increased level of ALAT and ASAT at 300 mg/kg, without any morphological changes seen at histopathology, and that recovered to normal levels in the recovery period. It can be discussed whether the 300 mg/kg dose should be regarded as NOAEL level for this study.

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:

0.83 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:

100 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

A 28-day study with AAI-PolyEA Amide resulted to an overall NOAEL of 100 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 not severe.

AF for differences in duration of exposure:

6

Justification:

The guidance indicates that for subacute to chronic a factor 6 should be applied.

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:

5

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. 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:

NOAEL of 100 mg/kg is possibly conservative. The NOAEL in based on an increased level of ALAT and ASAT at 300 mg/kg, without any morphological changes seen at histopathology, and that recovered to normal levels in the recovery period. It can be discussed whether the 300 mg/kg dose should be regarded as NOAEL level for this 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:

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.