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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.39 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEC
Value:
318 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
160 mg/m³
Explanation for the modification of the dose descriptor starting point:

Modification for exposure conditions workers vs. experimental: NOAEC x 6,7m3/10m3 x 6h/8h

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21.6 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Dose descriptor starting point:
LOAEC
Value:
480 mg/m³
Modified dose descriptor starting point:
LOAEC
Value:
810 mg/m³
Explanation for the modification of the dose descriptor starting point:

Clinical signs of respiratory tract irritation reversible within 24h and a slight body weight loss 24 hours after exposure was observed in rat exposed for 4 hours to 480 mg ethyldiisopropylamine/m3 in an acute inhalation toxicity study (Nagy, 2013). This value is used as PoD to derive a DNEL for the acute/short-term systemic effects by inhalation. As this LOAEC is for a 4 hours exposure, a LOAEC of 1210 mg/m3 was extrapolated with the Haber's law (n = 3) for a 15 min exposure. After adjustment for exposure duration and ventilation rate of workers, the NAEC is 810 mg/m3 (1210 mg/m3 x 6.7m3/10m3). 

AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
3
Justification:
conversion from LOAEC to NOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.4 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor:
NOAEC
Value:
30 mg/m³
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
The nasal irritation is not duration-related but driven but the concentration. The NOAECs for local nasal effects are consistent between the 28- and the 90-day inhalation exposure with DMEA (Van Triel 2019 and Beebe, 2021, respectively) are set at 10 ppm and used for risk assessment.
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21.6 mg/m³
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Dose descriptor starting point:
LOAEC
Value:
480 mg/m³
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
3
Justification:
Conversion LOAEC to NOAEC

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.22 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEC
Value:
318 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
922.22 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL derivation is based on a 90-day toxicity study by inhalation administration to rats (Beede, 2021). The starting dose for DNEL calculation is a NOAEC of 318 mg/m3 (106 ppm). Considering a ventilation rate of 0.29 m3/kg for a 6-hour exposure and a default inhalation absorption of 100%, the corresponding internal NOAEL is 92.22 mg/kg bw/d. DMEA is expected to be poorly absorbed by the skin (10% of the dose), therefore the dermal NAEL derived for workers is 922.2 mg/kg bw/d. 

AF for dose response relationship:
1
Justification:
Not needed
AF for differences in duration of exposure:
2
Justification:
Default AF
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
5
Justification:
Default AF
AF for the quality of the whole database:
1
Justification:
Not needed
AF for remaining uncertainties:
1
Justification:
Not needed
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)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.14 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEC
Value:
318 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
57.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

Modification for exposure conditions general population vs. experimental: NOAEC x 6h/24h x 5d/7d

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
additional intraspecies differences between workers and general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.2 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor:
NOAEC
Value:
30 mg/m³
AF for differences in duration of exposure:
1
Justification:
The nasal irritation is not duration-related but driven but the concentration. The NOAEC are consistent between the 28- and the 90-day inhalation exposure and are set at 10 ppm. The NOAEC of 10 ppm (30 mg/m") is used for risk assessment.
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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:
0.33 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Dose descriptor starting point:
NOAEC
Value:
318 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
65.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL derivation is based on a 90-day toxicity study by inhalation administration to rats with the analogue DMEA (Beebe, 2019). The starting dose for DNEL calculation is a NOAEC of 318 mg/m3 (106 ppm). Considering a ventilation rate of 0.29 m3/kg for a 6-hour exposure of rats and a default inhalation absorption of 100%, the corresponding internal NOAEL is 92.22 mg/kg bw/d. DMEA is expected to be readily absorbed by the GI tract (100% of the dose), therefore the oral NAEL derived for general populations after adjustment for exposure duration (7 days/week) is 65.8 mg/kg bw/d.


 

AF for dose response relationship:
1
Justification:
Not needed
AF for differences in duration of exposure:
2
Justification:
Default AF
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
10
Justification:
Default AF
AF for the quality of the whole database:
1
Justification:
Not needed
AF for remaining uncertainties:
1
Justification:
Not needed
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population