Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35.26 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):
50
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 763.15 mg/m³
Explanation for the modification of the dose descriptor starting point:

The oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences

between the 8-hour standard inhalation volume of rats versus humans, and for differences between the 8-hour inhalation volume of workers in rest versus workers in light activity, by multiplying with the corresponding factors (x 1/0.38 m³/kg/d x 6.7 m³/10 m³). The resulting corrected starting point for inhalation DNEL derivation for workers is equal to 1763.15 mg/m³.see discussion

AF for dose response relationship:
1
Justification:
no additional issues, default
AF for differences in duration of exposure:
2
Justification:
sub chronic to chronic, default
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling already considered in starting point conversion, see above
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
worker, default
AF for the quality of the whole database:
1
Justification:
no additional issues, default
AF for remaining uncertainties:
2
Justification:
oral to inhalation conversion, default
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 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):
100
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There is no data available indicating that dermal uptake is considerably lower than oral uptake.

The oral systemic long-term NOAEL was therefore considered appropriate for derivation of a dermal systemic long-term DNEL without further correction. Hence, the NOAEL oral is transferred to a NOAEL dermal without correction.

AF for dose response relationship:
1
Justification:
no additional issues, default
AF for differences in duration of exposure:
2
Justification:
sub chronic to chronic, default
AF for interspecies differences (allometric scaling):
4
Justification:
rat allometric scaling, default
AF for other interspecies differences:
2.5
Justification:
remainig differences, default
AF for intraspecies differences:
5
Justification:
worker, default
AF for the quality of the whole database:
1
Justification:
no quality issue, default
AF for remaining uncertainties:
1
Justification:
no further uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium 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

Worker:

Based on the available data “Reaction product of “Maleic anhydride, 2-Ethylhexylamine and Triethanolamine”, has to be considered as irritating to the skin (R38 according to Directive 67/548/EEC annex VI; Cat. 2 according to EC/1271/2008), posing the risk of serious eye damage (R41/Cat. 1) and potentially skin sensitizing (R43; Cat. 1B), respectively.

For the sensitization and skin or eye irritation potential, only a qualitative assessment can be conducted. Though such reactions of the skin are generally regarded as threshold effect, deriving a threshold and setting a DNEL is very difficult in practice especially based on common test systems because no dose-response data of the tested substance can be derived from test available here and therefore no quantitative determination of a DNEL for e.g. skin sensitization is possible.

The primary routes of anticipated industrial and professional exposure are via inhalation and skin contact. In industrial settings, ingestion is not an anticipated route of exposure, but has to be considered for the general population (see below).

Dermal short-term and long-term exposure – local effects:

As no dose response information for these local effects exists, the use of protective gloves and appropriate eye protection is mandatory for worker whenever a potential for relevant ocular or dermal exposure exists. RMM as well as information on the hazard of the substance are communicated via the safety data sheet. Further the workers are trained in using personal protective equipment which ensure the safe handling of the substance. Therefore the risk concerning skin sensitization, skin irritiation and eye damage is adequately communicated and RMMs are in place to assure the risk adequately controlled. (Further detailed information are given within the CSR)

 

Inhalation long-term exposure – systemic:

The NOAEL from an oral OECD Guideline 408 study (90d Test) (BASF SE, 2019) was identified as the most sensitive and appropriate starting point for DNEL derivation for long-term exposure following inhalation. The NOAEL for general, systemic toxicity of the test substance was 1000 mg/kg bw/d for rats within this subchronic study.

This point of departure was modified to get the corrected starting point for DNEL derivation. As a first step, route-to-route extrapolation was performed as recommended in the "Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 26 f.:

The oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between the 8-hour standard inhalation volume of rats versus humans, and for differences between the 8-hour inhalation volume of workers in rest versus workers in light activity, by multiplying with the corresponding factors (x 1/0.38 m³/kg/d x 6.7 m³/10 m³). The resulting corrected starting point for inhalation DNEL derivation for workers is equal to 1763.15 mg/m³.

For DNEL derivation, the following assessment factors (AF) according to ECHA default assumption are choosen:

- Interspecies factor: 1 (allometric scaling already considered in starting point conversion, see above)

- remaining Interspecies differences: 2.5 (default)

- Intraspecies factor: 5 (worker, default)

- Exposure duration: 2 (sub chronic to chronic, default)

- Dose-response: 1 (no additional issues, default)

- Oral to Inhalation additional default factor: 2

Total AF = 2.5 x 5 x 2 x 1 x 2 = 50

Based on this calculation the resulting DNEL inhalative, systemic, worker is 35.26 mg/m³.

 

Dermal long-term exposure – systemic effects:

The NOAEL from an oral OECD Guideline 408 study (90d Test) (BASF SE, 2019) was identified as the most sensitive and appropriate starting point for DNEL derivation for long-term exposure following inhalation. The NOAEL for general, systemic toxicity of the test substance was 1000 mg/kg bw/d for rats within this subchronic study.

There is no data available indicating that dermal uptake is considerably lower than oral uptake. The oral systemic long-term NOAEL was therefore considered appropriate for derivation of a dermal systemic long-term DNEL without further correction. Hence, the NOAEL oral is transferred to a NOAEL dermal without correction.

For DNEL derivation, the following assessment factors (AF) according to ECHA default assumption are choosen:

- Interspecies factor: 4 (rat allometic scaling, default)

- remaining Interspecies differences: 2.5 (default)

- Intraspecies factor: 5 (worker, default)

- Exposure duration: 2 (sub chronic to chronic, default)

- Dose-response: 1 (no additional issues, default)

 

Total AF = 4 x 2.5 x 5 x 2 x 1 = 100

Based on this calculation the resulting DNEL dermal, systemic, worker is 10 mg/kg bw/day.

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:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
869.56 mg/m³
Explanation for the modification of the dose descriptor starting point:

This point of departure was modified to get the correct starting point for DNEL derivation.

As a first step, route-to-route extrapolation was performed as recommended in the "Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 26 f.:

The oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between the 24-hour standard inhalation volume of rats versus humans by multiplying with the corresponding factor (x 1/1.15 m³/kg/d). The resulting corrected starting point for inhalation DNEL derivation for the general population is equal to 869.56 mg/m³.

AF for dose response relationship:
1
Justification:
no additional issue, default
AF for differences in duration of exposure:
2
Justification:
sub chronic to chronic, default
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling already considered in starting point conversion, see above
AF for other interspecies differences:
2.5
Justification:
remaining interspecies differences, default
AF for intraspecies differences:
10
Justification:
consumer, default
AF for the quality of the whole database:
1
Justification:
no additional issue, default
AF for remaining uncertainties:
2
Justification:
oral to inhalation conversion
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:
5 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):
200
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There is no data available indicating that dermal uptake is considerably lower than oral uptake. The oral systemic long-term NOAEL was therefore considered appropriate for derivation of a dermal systemic long-term DNEL without further correction.

Hence, the NOAEL oral is transferred to a NOAEL dermal without correction.

AF for dose response relationship:
1
Justification:
no additional issues, default
AF for differences in duration of exposure:
2
Justification:
sub chronic to chronic, default
AF for interspecies differences (allometric scaling):
4
Justification:
rat, default
AF for other interspecies differences:
2.5
Justification:
remaining differences, default
AF for intraspecies differences:
10
Justification:
consumer, default
AF for the quality of the whole database:
1
Justification:
no additional issues, default
AF for remaining uncertainties:
1
Justification:
no additional issues, default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 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):
200
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The NOAEL of 1000 mg/kg bw/day was considered appropriate as point of departure for DNEL derivation. No additional reduction were used.
AF for dose response relationship:
1
Justification:
no additional issues, default
AF for differences in duration of exposure:
2
Justification:
sub chronic to chronic, default
AF for interspecies differences (allometric scaling):
4
Justification:
rat, default
AF for other interspecies differences:
2.5
Justification:
remaining uncertainties, default
AF for intraspecies differences:
10
Justification:
consumer, default
AF for the quality of the whole database:
1
Justification:
no additional issues, default
AF for remaining uncertainties:
1
Justification:
no additional issues, default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

Consumer

Based on the available data “Reaction product of Maleic anhydride, 2-Ethylhexylamine and Triethanolamine”, has to be considered as irritating to the skin (R38 according to Directive 67/548/EEC annex VI; Cat. 2 according to EC/1271/2008), posing the risk of serious eye damage (R41/Cat. 1) and potentially skin sensitizing (R43; Cat. 1B), respectively.

For the sensitization and skin or eye irritation potential, only a qualitative assessment can be conducted. Though such reactions of the skin are generally regarded as threshold effect, deriving a threshold and setting a DNEL is very difficult in practice especially based on common test systems because no dose-response data of the tested substance can be derived from test available here and therefore no quantitative determination of a DNEL for e.g. skin sensitization is possible.

 

 

For the general population, all three possible routes of exposure (oral, dermal, inhalation) have to be taken into account.

Dermal short-term and long-term exposure – local effects:

As no dose response information for these local effects exists, the risk assessment for consumer is performed, if consumer uses are available on a qualitative base. (For detailed information see CSR)

 

Inhalation long-term exposure – systemic:

The NOAEL from an oral OECD Guideline 408 study (90d Test) (BASF SE, 2019) was identified as the most sensitive and appropriate starting point for DNEL derivation for long-term exposure following inhalation. The NOAEL for general, systemic toxicity of the test substance was 1000 mg/kg bw/d for rats within this subchronic study.

This point of departure was modified to get the correct starting point for DNEL derivation. As a first step, route-to-route extrapolation was performed as recommended in the "Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 26 f.:

The oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between the 24-hour standard inhalation volume of rats versus humans by multiplying with the corresponding factor (x 1/1.15 m³/kg/d). The resulting corrected starting point for inhalation DNEL derivation for the general population is equal to 869.56 mg/m³.

For DNEL derivation, the following assessment factors (AF) according to ECHA default assumption are choosen:

- Interspecies factor: 1 (allometric scaling already considered in starting point conversion, see above)

- remaining Interspecies differences: 2.5

- Intraspecies factor: 10 (consumer, default)

- Exposure duration: 2 (sub chronic to chronic, default)

- Dose-response: 1 (no additional issues, default)

- Oral to Inhalation additional default factor: 2

Total AF = 2.5 x 5 x 2 x 1 x 2 = 100

Based on this calculation the resulting DNEL inhalation, systemic, consumer is 8.7 mg/m³.

 

 

Dermal long-term exposure – systemic effects:

The NOAEL from an oral OECD Guideline 408 study (90d Test) (BASF SE, 2019) was identified as the most sensitive and appropriate starting point for DNEL derivation for long-term exposure following inhalation. The NOAEL for general, systemic toxicity of the test substance was 1000 mg/kg bw/d for rats within this subchronic study.

There is no data available indicating that dermal uptake is considerably lower than oral uptake. The oral systemic long-term NOAEL was therefore considered appropriate for derivation of a dermal systemic long-term DNEL without further correction. Hence, the NOAEL oral is transferred to a NOAEL dermal without correction.

For DNEL derivation, the following assessment factors (AF) according to ECHA default assumption are choosen:

- Interspecies factor: 4 (rat, default)

- remaining Interspecies differences: 2.5 (default)

- Intraspecies factor: 10 (consumer, default)

- Exposure duration: 2 (sub chronic to chronic, default)

- Dose-response: 1 (no additional issues, default)

 

Total AF = 4 x 2.5 x 10 x 2 x 1 = 200

Based on this calculation the resulting DNEL dermal, systemic, consumer is 5 mg/kg bw/day.

 

Oral long-term exposure – systemic effects:

The NOAEL from an oral OECD Guideline 408 study (90d Test) (BASF SE, 2019) was identified as the most sensitive and appropriate starting point for DNEL derivation for long-term exposure following inhalation. The NOAEL for general, systemic toxicity of the test substance was 1000 mg/kg bw/d for rats within this subchronic study.

The NOAEL of 1000 mg/kg bw/day was considered appropriate as point of departure for DNEL derivation. No additional reduction were used.

For DNEL derivation, the following assessment factors (AF) according to ECHA default assumption are choosen:

- Interspecies factor: 4 (rat, default)

- remaining Interspecies differences: 2.5 (default)

- Intraspecies factor: 10 (consumer, default)

- Exposure duration: 2 (sub chronic to chronic, default)

- Dose-response: 1 (no additional issues, default)

Total AF = 4 x 2.5 x 10 x 2 x 1 = 200

Based on this calculation the resulting DNEL oral, systemic, consumer is 5 mg/kg bw/day.