Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.54 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):
30
Dose descriptor starting point:
LOAEL
Value:
33 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
16.3 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral LOAEL observed in a chronic repeated dose oral toxicity study (Yanagisawa, 1998).

To correct the interspecies difference between rat and human the lowest observed effect level has to be corrected as follows:

Corrected starting point for the inhalative route for workers:

= LOAEL(oral) * (1/0.38 m³/kg bw/day) * (ABSoral-rat/ABSinh-human) * 6.7 m³ (8h) /10 m³ (8h) * (7 days of exposure rat/5 days of exposure worker)

= 33 mg/kg bw/day * (1/0.38 m³/kg bw/day) * (20%/100%) * 0.67 m³ * 1.4= 16.3 mg/m³

For intestinal absorption a figure of 20% has been estimated (based on rat data). Inhalation absorption was estimated to be 100% (no data).

(ABSoral-rat = oral absorption in rats, ABSinh-human = inhalation absorption rate in humans)

Thus, the corrected starting point for workers was 16.3 mg/m³ for inhalation.

AF for dose response relationship:
3
Justification:
The dose descriptor starting point is based on a LOAEL. 50 mg TETA.2HCl/kg bw/day (corresponding to 33 mg Amines, polyethylenepoly-, triethylenetetramine fraction/kg bw/day was a NOAEL in females but a LOAEL in males.
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable
AF for other interspecies differences:
1
Justification:
rats and dogs showed similar NOAELs following 26 weeks of exposure; mice showed a 2-times higher NOAEL at a 2-times shorter duration (13 weeks), indicating that interspecies effect concentrations are small if at all
AF for intraspecies differences:
5
Justification:
Default value according to ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
no additional assessment factor is needed
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

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:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

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)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium 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:
0.096 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):
60
Dose descriptor starting point:
NOAEL
Value:
33 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
5.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral LOAEL observed in a chronic repeated dose oral toxicity study (Yanagisawa, 1998).

To correct the interspecies difference between rat and human the lowest observed effect level has to be corrected as follows:

Corrected starting point for the inhalative route for general population:

= LOAEL(oral) * (1/1.15 m³/kg bw/day(24h)) * (ABSoral-rat/ABSinh-human)

= 33 mg/kg bw/day * (1/1.15 m³/kg bw/day) * (20%/100%) = 5.7 mg/m³

For intestinal absorption a figure of 20% has been estimated (based on rat data). Inhalation absorption was estimated to be 100% (no data).

(ABSoral-rat = oral absorption in rats, ABSinh-human = inhalation absorption rate in humans)

Thus, the corrected starting point for workers was 5.7 mg/m³ for inhalation.

AF for dose response relationship:
3
Justification:
The dose descriptor starting point is based on a LOAEL. 50 mg TETA.2HCl/kg bw/day (corresponding to 33 mg Amines, polyethylenepoly-, triethylenetetramine fraction/kg bw/day) was a NOAEL in females but a LOAEL in males.
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
not applicable
AF for other interspecies differences:
1
Justification:
rats and dogs showed similar NOAELs following 26 weeks of exposure; mice showed a 2-times higher NOAEL at a 2-times shorter duration (13 weeks), indicating that interspecies effect concentrations are small if at all
AF for intraspecies differences:
10
Justification:
Default value according to ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
no additional assessment factor is needed
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

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

General Population - Hazard via dermal route

Systemic 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

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)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.14 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):
240
Dose descriptor starting point:
LOAEL
Value:
33 mg/kg bw/day
AF for dose response relationship:
3
Justification:
The dose descriptor starting point is based on a LOAEL. 50 mg TETA.2HCl/kg bw/day (corresponding to 33 mg Amines, polyethylenepoly-, triethylenetetramine fraction/kg bw/day) was a NOAEL in females but a LOAEL in males.
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
The experimental animal was a rat.
AF for other interspecies differences:
1
Justification:
rats and dogs showed similar NOAELs following 26 weeks of exposure; mice showed a 2-times higher NOAEL at a 2-times shorter duration (13 weeks), indicating that interspecies effect concentrations are small if at all
AF for intraspecies differences:
10
Justification:
Default value according to ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
no additional assessment factor is needed
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population