Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.96 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: MAK Commission, DFG
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:
0.21 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
LOAEL
DNEL value:
31.68 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No data are available for LAS DEA. Dermal LOAEL for DEA is determined to be 8 mg/kg bw/day. The dermal LOAEL for LAS DEA was calculated by scaling based on the molecular weight. The conversion factor from DEA to LAS DEA is 3.96. Therefore, the dermal LOAEL for LAS DEA = 31.68 mg/kg bw/day. No further correction of the dermal LOEAL is needed.

AF for dose response relationship:
3
Justification:
The assessment factor was used for extrapolation from LOAEL to NOAEL.
AF for differences in duration of exposure:
1
Justification:
No time extrapolation factor is needed since a chronic toxicity study is available.
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
2.5
Justification:
The default factor for the other interspecies differences is used.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "worker" is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium 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

No acute toxicity data for LAS DEA is available. However, based on information of both read-across substances LAS NA and DEA, LAS DEA shall also be classified for acute oral toxicity.

 

An acute DNEL for inhalation and dermal route is not derived as LAS DEA is not classified for acute systemic toxicity via the dermal or inhalation route and acute effects are covered sufficiently by long-term DNEL. Furthermore, inhalation exposure is considered the least relevant route, and high peak exposures through inhalation are not expected to occur.

 

LAS DEA is a skin irritant (Skin Irrit. 2, H315) and damaging to the eyes (Eye Dam. 1, H318). However, no dose-response data are available and hence, a DNEL cannot be derived for these endpoints. Therefore, a qualitative assessment is performed.

 

No repeated dose toxicity studies were performed with LAS DEA. Therefore, this endpoint was addressed with data from LAS Na and DEA.

 

Regarding inhalation route, a MAK (occupational exposure level, OEL) value of 1 mg/m^3 was established for DEA in Germany (please refer to REACH registration dossier of Diethanolamine and Deutsche Forschungsgemeinschaft, DFG, “MAK-Collection”). This value represents an appropriate toxicological threshold value. Therefore, no DNEL was derived. Conversion factor for DEA to LAS DEA is 3.96 based on molecular weight scaling. Therefore, corresponding threshold is 1 x 3.96 mg/m3 air for local long-term inhalation DNEL.

MAK value is based on local effects which are more critical compared to systemic effects after inhalation of DEA. Therefore, systemic DNEL is not derived as it is covered by local DNEL.

 

As DEA is not classified for acute inhalation toxicity, no acute DNEL is needed.

 

Dermal LOAEL for DEA is determined to be 8 mg/kg bw/day in female rats based on available chronic dermal toxicity studies with rats and mice. The critical systemic effects appear to be kidney and liver toxicity and anaemia. Besides anaemia, nephropathy was observed at the lowest tested dose in the 13 weeks dermal toxicity study (32 mg/kg bw/day in rats). After 13 weeks kidney effects are not yet masked by ageing. Therefore, the observation of nephropathy in female rats at the lowest tested dermal dose of 8 mg/kg bw/day in the 2 year study, which was somewhat masked by ageing, is also considered adverse (Please also refer to the REACH registration dossier of DEA). The dermal LOAEL for LAS DEA was calculated by scaling based on the molecular weight of the substance.

The conversion factor of DEA is 3.96. The dermal LOAEL LAS DEA = 31.68 mg/kg bw/day.

 

This dermal LOAEL was used in order to derive a dermal DNEL.

 

Assessment factors used:

Dose-response relationship (LOAEL -> NOAEL): 3

Allometric scaling (rat): 4

Intraspecies (workers): 5    

Residual interspecies: 2.5  

Differences in duration (chronic to chronic): 1    

AF total: 150

This results in a dermal DNELlong-term = 0.21 mg/kg bw/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.99 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: MAK Commission, DFG
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:
0.1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
LOAEL
DNEL value:
31.68 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No data are available for LAS DEA. Dermal LOAEL for DEA is determined to be 8 mg/kg bw/day.The dermal LOAEL for LAS DEA was calculated by scaling based on the molecular weight. The conversion factor from DEA to LAS DEA is 3.96. Therefore, the dermal LOAEL for LAS DEA = 31.68 mg/kg bw/day. No further correction of the dermal LOEAL is needed.

AF for dose response relationship:
3
Justification:
The assessment factor was used for extrapolation from LOAEL to NOAEL.
AF for differences in duration of exposure:
1
Justification:
No time extrapolation factor is needed since a chronic toxicity study is available.
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
2.5
Justification:
The default factor for the other interspecies differences is used.
AF for intraspecies differences:
10
Justification:
The default value for the relatively heterogenous group "population" is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.09 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):
600
Dose descriptor starting point:
LOAEL
DNEL value:
55.44 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Lowest oral LOAEL for DEA is determined to be 14 mg/kg bw/day in rats based on available 90 days repeated dose toxicity study based on anaemia, nephrotoxicity, increased kidney weight. (Please also refer to the REACH registration dossier of DEA). The oral LOAEL for LAS DEA was calculated by scaling based on the molecular weight of the substance. The conversion factor of DEA is 3.96. The oral LOAEL LAS DEA = 55.44 mg/kg bw/day.

AF for dose response relationship:
3
Justification:
The assessment factor was used for extrapolation from LOAEL to NOAEL.
AF for differences in duration of exposure:
2
Justification:
The default assessment factor was used for extrapolation from sub-chronic to chronic exposure.
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
2.5
Justification:
The default factor for the other interspecies differences is used.
AF for intraspecies differences:
10
Justification:
The default value for the relatively heterogenous group "population" is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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

No acute toxicity data for LAS DEA is available. However, based on information of both read-across substances LAS NA and DEA, LAS DEA shall also be classified for acute oral toxicity.

 

An acute DNEL for inhalation and dermal route is not derived as LAS DEA is not classified for acute systemic toxicity via the dermal or inhalation route and acute effects are covered sufficiently by long-term DNEL. Furthermore, inhalation exposure is considered the least relevant route, and high peak exposures through inhalation are not expected to occur.

 

LAS DEA is a skin irritant (Skin Irrit. 2, H315) and damaging to the eyes (Eye Dam. 1, H318). However, no dose-response data are available and hence, a DNEL cannot be derived for these endpoints. Therefore, a qualitative assessment is performed.

 

No repeated dose toxicity studies were performed with LAS DEA. Therefore, this endpoint was addressed with data from LAS Na and DEA.

 

There are three repeated dose oral toxicity studies with LAS Na. The lowest LOAEL is 115 mg/kg bw., observed in a 6-month rat study (Yoneyama et al., 1972). The highest NOAEL below this LOAEL is 85 mg/kg bw observed in a 9-month rat study (Yoneyama et al., 1976). In view of the available information it is not possible to determine which single study among those is the most reliable or appropriate for the determination of a NOAEL. Therefore, based on the data from all the studies, a NOAEL of 85 mg/kg bw is proposed, which was derived from a 9- month oral study and corresponds to the NOAEL, which is closest to the lowest available oral LOAEL of 115 mg/kg bw.

 

The lowest oral LOAEL observed in a 90 days repeated dose toxicity studies with DEA was 14 mg/kg bw/day in rats and hence, DEA is much more toxic than LAS Na. Consequently, the threshold value for LAS DEA is based on the hazardous properties of DEA.

 

Regarding inhalation route, a MAK (occupational exposure level, OEL) value of 1 mg/m^3 was established in Germany for diethanolamine (please refer to REACH registration dossier of Diethanolamine and Deutsche Forschungsgemeinschaft, DFG, “MAK-Collection”). This value represents an appropriate toxicological threshold value. Therefore, no DNEL was derived. Conversion factor for DEA to LAS DEA is 3.96 based on molecular weight scaling. This converted value is used as a starting point for local long-term inhalation DNEL derivation for general population. Modification is based on differences in exposure duration and activity (10m^3 in 8 h for workers, 20 m^3 in 24 h for the general population) and applying a correction for intra species differences (workers default factor 5, general population default factor: 10)

 MAK value is based on local effects which are more critical compared to systemic effects after inhalation of DEA. Therefore, systemic DNEL is not derived as it is covered by local DNEL.

 

As DEA is not classified for acute inhalation toxicity, no acute DNEL is needed.

 

Dermal LOAEL for DEA is determined to be 8 mg/kg bw/day in female rats based on available chronic dermal toxicity studies with rats and mice. The critical systemic effects appear to be kidney and liver toxicity and anaemia. Besides anaemia, nephropathy was observed at the lowest tested dose in the 13 weeks dermal toxicity study (32 mg/kg bw/day in rats). After 13 weeks kidney effects are not yet masked by ageing. Therefore, the observation of nephropathy in female rats at the lowest tested dermal dose of 8 mg/kg bw/day in the 2 year study, which was somewhat masked by ageing, is also considered adverse (Please also refer to the REACH registration dossier of DEA). The dermal LOAEL for LAS DEA was calculated by scaling based on the molecular weight of the substance.

The conversion factor of DEA is 3.96. The dermal LOAEL LAS DEA = 31.68 mg/kg bw/day.

 

This dermal LOAEL was used in order to derive a dermal DNEL.

 

Assessment factors used:

Dose-response relationship (LOAEL -> NOAEL): 3

Allometric scaling (rat): 4

Intraspecies (general population): 10    

Residual interspecies: 2.5  

Differences in duration (chronic to chronic): 1    

AF total: 300

This results in a dermal DNELlong-term = 0.1 mg/kg bw/day.

Lowest oral LOAEL for DEA is determined to be 14 mg/kg bw/day in rats based on available 90 days repeated dose toxicity study based on anaemia, nephrotoxicity, increased kidney weight. (Please also refer to the REACH registration dossier of DEA). The oral LOAEL for LAS DEA was calculated by scaling based on the molecular weight of the substance. The conversion factor of DEA is 3.96. The oral LOAEL LAS DEA = 55.44 mg/kg bw/day. This oral LOAEL was used in order to derive an oral DNEL.

 

Assessment factors used:

Dose-response relationship (LOAEL -> NOAEL): 3

Allometric scaling (rat): 4

Intraspecies (general population): 10    

Residual interspecies: 2.5  

Differences in duration (sub-chronic to chronic): 2    

AF total: 600

This results in a oral DNELlong-term = 0.09 mg/kg bw/day.