Amides, from C18-unsatd. fatty acids and tetraethylenepentamine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

29 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC/ECHA

Overall assessment factor (AF):

18

Modified dose descriptor starting point:

NOAEC

Value:

529 mg/m³

AF for differences in duration of exposure:

6

Justification:

Sub-acute to chronic

AF for intraspecies differences:

3

Justification:

ECETOC concept (combined inter-/intraspecies differences)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

176 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC/ECHA

Overall assessment factor (AF):

3

Modified dose descriptor starting point:

NOAEC

Value:

529 mg/m³

AF for intraspecies differences:

3

Justification:

ECETOC concept (combined inter-/intraspecies differences)

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.2 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

other: ECETOC/ECHA

Overall assessment factor (AF):

72

Modified dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

AF for differences in duration of exposure:

6

Justification:

Sub-acute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

Default

AF for intraspecies differences:

3

Justification:

ECETOC concept (combined inter-/intraspecies differences)

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

Most sensitive endpoint:

skin irritation/corrosion

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.3 % in mixture (weight basis)

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

DNEL derivation method:

other: Refer to discussion

Overall assessment factor (AF):

3

Dose descriptor:

other: NOAEL

AF for intraspecies differences:

3

Justification:

Refer to discussion

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.3 % in mixture (weight basis)

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

DNEL derivation method:

other: Refer to discussion

Overall assessment factor (AF):

3

Dose descriptor starting point:

other: NOAEL

AF for intraspecies differences:

3

Justification:

Refer to discussion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - workers

Workers:

Acute / Short-term – systemic effects

Dermal DNEL

No threshold effect: Substance is corrosive and sensitising. Effects following dermal exposures will be characterized by local corrosive and possible sensitizing 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 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.)

 

Inhalation DNEL

Substance is corrosive and sensitizing.The likelihood for exposure via inhalation and thus experience respiratory irritation or becoming sensitised to AAI, is very lowconsidering the high boiling point (> 300 °C) and very low vapour pressure (0.00017 mPa at 25°C for DETA based AAI). In case of high exposure by inhalation, local effects will be more prominent then possible systemic effects considering the low systemic toxicity seen in acute oral toxicity testing

 

However, some calculations can be made for systemic effects following short-term inhalation exposure by extrapolating information from anOECD 422 study on Tall oil reaction products with tetraethylene-pentamine (Amidoamine/Imidazoline) showing a NOAEL of 300 mg/kg/day. This would certainly be protective for levels of acute inhalation expected to lead to similar systemic exposure levels.

The corrected 8 hr inhalation NOAEC for workers is NOAEL (300 mg/kg) * 1.76 mg/m3 = 529 mg/m3 (assuming no difference in absorption following oral and inhalation exposure). Assessment factors further applied: No interspecies factor is needed due to allometric scaling applied in calculation of corrected NOAEC. Further combined inter-/intraspecies for workers AF = 3 (ECETOC concept). As this involves acute exposures, no extrapolation for duration is needed.

This results in a DNEL of 529/3 = 176 mg/m3.A short term/acute exposure at this level can be assumed not to lead to systemic toxicity.

 

 

Acute / Short term – local effects

Dermal DNEL

Substance is corrosive and sensitizing. For 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.)

An indication for possible threshold effects for irritation comes from an available sensitisation study on Fatty acids C16-18, C18 unsat reaction products with tetraethylenepentamine. In a GPMT 1% in an aqueous solution (0.9% NaCl) was found to be non-irritant (0.5 mL, 24 hrs, occlusive on rabbit skin).

This level could be used for indication of DNEL for local irritating effects. No interspecies AF is required. An AF of 3 is proposed to cover for intra-species variation for workers, leading to a DNEL for short-term local dermal effects of about 0.3%.

 

Inhalation DNEL

Substance is corrosive and sensitizing.The likelihood for exposure via inhalation, and thus experience respiratory irritation or becoming sensitised to AAI, is very lowconsidering the high boiling point (> 300 °C) and very low vapour pressure (0.00017 mPa at 25°C for DETA based AAI). Furthermore, as the substance is classified as corrosive, no acute toxicity testing should normally be conducted. As there are no data on local effects,no inhalation DNEL can be established for local effects.

 

Long-term exposure – systemic effects

Dermal DNEL

Substance is corrosive and sensitising. Effects following dermal exposures will be characterized by local corrosive effects that are related to duration, quantity and concentration of the substance, rather than by systemic toxicity due to dermal uptake. However, a DNEL can be derived by route-to-route extrapolation from an oral NOAEL.An OECD 422 combined 28-day/reproduction screening study resulted to an overall NOAEL of 300 mg/kg/day being the highest dose level tested.

Derived dermal NOAEL would be 300 mg/kgbw/d (assuming same dermal and oral absorption as worst case) and the following assessment factors: AF = 4 for allometric scaling (default). Combined inter-/intra-species for workers AF = 3 (ECETOC concept). Exposure duration from sub-acute to chronic AF = 6.

This results in a total assessment factor of 4 x 3 x 6 = 72, indicating that the DNEL will be 300/72 = 4.2 mg/kg bw/day.

 

Inhalation DNEL(aerosol)

An OECD 422 combined 28-day/reproduction screening study resulted to an overall NOAEL of 300 mg/kg/day being the highest dose level tested.

For aerosol inhalation absorption the following is suggested: Assumed is that the major part of the inhaled substance will be deposited in the upper respiratory tract, which will finally be taken up orally. No difference in absorption is considered between inhalation and oral ingestion.

The corrected 8 hr inhalation NOAEC for workers is NOAEL(300 mg/kg) * 1.76 mg/m3 = 529 mg/m3.

Further assessment factors applied: No interspecies factor is needed due to allometric scaling applied in calculation of corrected NOAEC. Combined inter-/intra-species for workers AF = 3 (ECETOC concept). Exposure duration from sub-acute to chronic AF = 6.

This results in a total assessment factor of 3 x 6 = 18, indicating that the DNEL will be 529/18 = 29 mg/m3.

 

 

Long-term exposure – local effects

Dermal DNEL

Substance is corrosive and sensitizing. For 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.).

Considered is that protection of irritation for short-term exposures, is also protective for irritation following repeated exposures. An indication for possible threshold effects for irritation comes from an available sensitisation study on Fatty acids C16-18, C18 unsat reaction products with tetraethylenepentamine. In a GPMT 1% in an aqueous solution (0.9% NaCl) was found to be non-irritant (0.5 mL, 24 hrs, occlusive on rabbit skin). This level could be used for indication of DNEL for local irritating effects. No interspecies AF is required. An AF of 3 is proposed to cover for intra-species variation for workers, leading to a DNEL for local dermal irritation of about 0.3%.

 

Inhalation DNEL

Substance is corrosive and sensitizing.The likelihood for exposure via inhalation and thus experience respiratory irritation or becoming sensitised to AAI, is very lowconsidering the high boiling point (> 300 °C) and very low vapour pressure (0.00017 mPa at 25°C for DETA based AAI). Furthermore, as the substance is classified as corrosive, no acute toxicity testing should normally be conducted. As there are no data on local effects,no inhalation DNEL can be established for local effects.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.7 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC/ECHA

Overall assessment factor (AF):

30

Modified dose descriptor starting point:

NOAEC

Value:

261 mg/m³

Explanation for the modification of the dose descriptor starting point:

Refer tp discussion

AF for differences in duration of exposure:

6

Justification:

Sub-acute to chronic

AF for intraspecies differences:

5

Justification:

ECETOC - Combined inter-/intraspecies for consumers/general population

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

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:

2.5 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC/ECHA

Overall assessment factor (AF):

120

Modified dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Refer to discussion

AF for differences in duration of exposure:

6

Justification:

Sub-acute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

Default

AF for intraspecies differences:

5

Justification:

Combined inter-/intraspecies for consumers/general population

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

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)

General Population - Hazard via oral 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:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC/ECHA

Overall assessment factor (AF):

120

Modified dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

AF for differences in duration of exposure:

6

Justification:

Sub-acute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

Default

AF for intraspecies differences:

5

Justification:

Combined inter-/intraspecies for consumers/general population

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

hazard unknown (no further information necessary)

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 evaluatepossible secondary exposures via environment, additionally long-term systemic DNELs for general population have been derived.

 

 

Long-term exposure – systemic effects

Dermal DNEL

Substance is corrosive and sensitising. Effects following dermal exposures will be characterized by local corrosive effects that are related to duration, quantity and concentration of the substance, rather than by systemic toxicity due to dermal uptake. However, a DNEL can be derived by route-to-route extrapolation from an oral NOAEL. An OECD 422 combined 28-day/reproduction screening study resulted to an overall NOAEL of 300 mg/kg/day being the highest dose level tested.

Derived dermal NOAEL would be 300 mg/kgbw/d (assuming same dermal and oral absorption as worst case for dermal exposures). The following assessment factors are used for the oral and dermal DNEL:

- AF = 4 for allometric scaling (default).

- Combined inter-/intra-species for consumers/general population: AF = 5 (ECETOC concept).

- Exposure duration from sub-acute to chronic AF = 6.

This results in a total assessment factor of 4 x 5 x 6 = 120. This leads to a consumer/general public long-term DNEL for systemic effects via dermal or oral exposures of 300/120 = 2.5 mg/kg bw/day.

 

Inhalation DNEL(aerosol)

An OECD 422 combined 28-day/reproduction screening study resulted to an overall NOAEL of 300 mg/kg/day being the highest dose level tested.

For aerosol inhalation absorption the following is suggested: Assumed is that the major part of the inhaled substance will be deposited in the upper respiratory tract, which will finally be taken up orally. No difference in absorption is considered between inhalation and oral ingestion.

The corrected 8 hr inhalation NOAEC for general population is NOAEL(300 mg/kg) * 1/1.15 mg/m3 = 261 mg/m3.

Further assessment factors applied:

- No interspecies factor is needed due to allometric scaling applied in calculation of corrected NOAEC.

- Combined inter-/intra-species for consumers/general population: AF = 5 (ECETOC concept).

- Exposure duration from sub-acute to chronic AF = 6.

This results in a total assessment factor of 5 x 6 = 30, indicating that the DNEL will be 261/30 = 8.7 mg/m3.