Fatty acids, C18-unsatd., reaction products with diethylenetriamine, acetates

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.47 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

36

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

Hazard assessment conclusion:

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

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

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

Acute/short term exposure

Hazard assessment conclusion:

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

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.21 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

144

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

Hazard assessment conclusion:

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

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

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

Acute/short term exposure

Hazard assessment conclusion:

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

Additional information - workers

The substance is classified for human health as a skin irritant, corrosive to eyes and as a skin sensitiser.

Workers:

Acute/short-term systemic effects:

Dermal DNEL:

A dermal DNEL has not been derived for short-term systemic effects. An acute dermal toxicity study showed no signs of systemic toxicity. The substance is not classified for acute dermal toxicity. It is considered to be unnecessary to derive an acute systemic dermal DNEL It is considered that dermal effects will be characterised by local tissue damage (skin irritation) and sensitising effects rather than by systemic effects due to dermal uptake.

For substances which are classified as irritating to the skin, appropriate PPE should be used by all workers. As a result, direct dermal contact should only occur infrequently or accidentally.

Inhalation DNEL:

No acute DNEL has been derived for short-term systemic effects arising from inhalation exposure.

The substance is not considered to be volatile taking into account the predicted vapour pressure of the substance constituents (ranging from 1.23 x 10-25 Pa to 4.0 x 10-16 Pa at 25°C) , high boiling point (estimated >300°C) and high viscosity of the substance. Inhalation is therefore not considered to be a significant route of exposure.

In case high exposure by the inhalation route did occur, it is anticipated that local effects would be more prominent then possible systemic effects considering the low systemic toxicity seen in acute oral and dermal testing.

Acute/short-term local effects:

Dermal DNEL:

The substance is classified as a skin irritant and skin sensitiser. An in-vivo skin irritation study showed moderate to severe erythema and oedema and an acute dermal toxicity study also showed evidence of dermal irritation. However, the skin irritation study does not provide suitable dose-response information to derive a DNEL for local effects. Dermal effects will be characterised by local tissue damage/irritation and sensitising effects.

For substances which are classified as irritating to the skin, appropriate PPE should be used by all workers. As a result, direct dermal contact should only occur infrequently or accidentally and substantial dermal exposure should not occur.

Inhalation DNEL:

No acute DNEL has been derived for short-term local effects arising from inhalation exposure.

The substance is not considered to be volatile taking into account the predicted vapour pressure of the substance constituents (ranging from 1.23 x 10-25 Pa to 4.0 x 10-16 Pa at 25°C), high boiling point (estimated >300°C) and high viscosity of the substance. Inhalation is therefore not considered to be a significant route of exposure.

In case high exposure via the inhalation route did occur, it is anticipated that local effects would be more prominent then possible systemic effects based on the irritant properties of the substance i.e. irritation of the respiratory tract would be a likely local effect.

Long-term exposure - systemic effects

Dermal DNEL:

A DNEL has been derived for long-term systemic effects by the dermal route. The substance is a skin irritant and sensitiser and therefore effects following dermal exposure will be characterised by local irritant effects that are related to duration, quantity and concentration of the substance, rather than by systemic toxicity due to dermal intake. Appropriate PPE should been used by all workers and therefore repeated substantial dermal exposure is unlikely.

However, a DNEL has been derived by route-to-route extrapolation from an oral NOAEL. An OECD 422 combined 28-day/reproduction screening study on Tall oil diethylenetriamine imidazoline (a structural analogue read-across substance) resulted in an overall NOEAL (for systemic toxicity) of 30 mg/kg bw/day.

The dermal NOAEL is assumed to be 30 mg/kg bw/day (assuming same dermal and oral absorption as worst case). The following assessment factors were then applied: AF 4 for allometric scaling (default). Combined inter-/intra species differences for workers AF 3 (ECETOC concept). Exposure duration from sub-acute to chronic AF 6. An additional assessment factor of 2 was also used to address the additional uncertainty factor of using read-across data. This results in an overall assessment factor of 144.

The DNEL is therefore 30 mg/kg bw/day / 144 = 0.21 mg/kg bw/day.

This long-term dermal systemic effect DNEL is used in the quantitative assessment of risk for systemic toxicity to workers via the dermal route.

Inhalation DNEL:

A DNEL has been derived for long-term systemic effects by the inhalation route. The DNEL is derived by route-to-route extrapolation from an oral NOAEL. An OECD 422 combined 28-day/reproduction screening study on Tall oil diethylenetriamine imidazoline (a structural analogue read-across substance) resulted in an overall NOEAL (for systemic toxicity) of 30 mg/kg bw/day.

For inhalation absorption, the following is suggested: It is assumed that the major part of the inhaled substance will be deposited in the upper respiratory tract, which will finally be taken up orally. Therefore no difference in absorption is considered between inhalation and oral routes.

The corrected 8 hr inhalation NOAEC for workers is NOAEL (30 mg/kg bw/day) x 1.76 mg/m3 = 52.8 mg/m3.

The corrected dose descriptor (NOAEC) for inhalation was calculated in accordance with the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health.

The conversion of an oral rat NOAEL into a corrected inhalatory NOAEC to assess human inhalatory exposure was performed using the modification of starting point equation as given in Figure R. 8-3 (see below) for workers (in the case of 8 hour exposure/day).

Default parameters for rats and human (for 8 hour exposure) were used for the modification of starting point under the allometric scaling principle as given in Table R. 8-2 of the above ECHA guidance.

Figure R.8-3 Modification of the starting point:

Conversion of an oral rate N(L) OAEL into a correct inhalatory N(L) OAEC to assess human inhalatory exposure:

For workers (in case of 8h exposure/day):

Corrected inhalatory N(L) OAEC = oral N(L) OAEL x (1 / sRVrat) x (ABSoral-rat / ABSinh-human) x (sRVhuman / wRV)

 Corrected inhalatory N(L) OAEC= 30 mg/kg bw/day x (1 / 0.38 m³/kg/d) x (1 / 1) x (6.7 m³(8h) / 10 m³(8h))

                                                        = 52.8 mg/m³

 Where:

ABS: Absorption

sRV: standard Respiratory Volume

wRV: worker Respiratory Volume (light activity)

 Default parameters:

sRVrat (8 h): 0.38m³/kg bw

sRVhuman (8 h): 6.7 m³/ person

wRV (8 h): 10 m³/ person

The following assessment factors were then applied: No interspecies factor is needed due to allometric scaling applied in the calculation of corrected NOAEC. Combined inter-/intra-species for workers AF = 3 (ECETOC concept). Expososure duration for sub-acute to chronic AF =6. An additional assessment factor of 2 was also used to address the additional uncertainty factor of using read-across data. This results in an overall assessment factor of 36.

Conversion of corrected inhalatory NOAEC into a long-term DNEL (inhalation) of workers:

 DNEL (inhalation)= Inhalatory NOAEC / Overall assessment factor = 52.8 mg/m³/ 36 = 1.47 mg/m³

This long-term dermal systemic effect DNEL is used in the quantitative assessment of risk for systemic toxicity to workers via the inhalation route.

Long-term exposure - local effects

Dermal DNEL:

No DNEL has been derived for long-term dermal local effects. No long-term dermal study has been conducted and available short-term studies do not give adequate dose-response data.

The substance is a skin irritant and sensitiser and therefore effects following dermal exposure will be characterised by local irritant effects that are related to duration, quantity and concentration of the substance. Appropriate PPE should been used by all workers and therefore repeated substantial dermal exposure is unlikely.

Inhalation DNEL:

No DNEL has been derived for long-term inhalation local effects as no long-term inhalation study has been conducted and therfore there is no data on local effects.

The substance is not considered to be volatile taking into account the predicted vapour pressure of the substance constituents (ranging from 1.23 x 10-25 Pa to 4.0 x 10-16 Pa at 25°C), high boiling point (estimated >300°C) and high viscosity of the substance. Inhalation is therefore not considered to be a significant route of exposure.

In case high repeated exposure via the inhalation route did occur, it is anticipated that local effects would be more prominent then possible systemic effects based on the irritant properties of the substance i.e. irritation of the respiratory tract would be a likely local effect.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

exposure based waiving

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

exposure based waiving

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

exposure based waiving

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

exposure based waiving

Acute/short term exposure

Hazard assessment conclusion:

exposure based waiving

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.125 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

240

Modified dose descriptor starting point:

NOAEL

Value:

30 mg/kg bw/day

Acute/short term exposure

Hazard assessment conclusion:

exposure based waiving

DNEL related information

Additional information - General Population

DNELs have not been derived for the general public (apart from via the oral route for systemic effects) as there will be no exposure to the general public/consumers.

The substance will only be used by industry and not by the public. Due to minimal release of the substance from industrial use, exposure to the general public is not anticipated. However, a DNEL for long term systemic effects via the oral route has been derived, in order to assess indirect exposure of humans via the environment.