Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.9 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):
25
Dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
123.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

The substance has shown not to cause reproduction effects up to 50 mg/kg bw/d in an OECD 422 study covering the full developmental period. At this level some local irritation in the stomach was observed in the absence of systemic effects. A developmental toxicity study (OECD 414) in rats showed no developmental toxicity up to 75 mg/kg bw, at which level maternal toxicity consisted of local irritation in the stomach. In this case the DNEL for systemic toxicity is based in highest level tested in 90-day (OECD 408) study showing no local effects in stomach and showing no systemic toxicity at 50 mg/kg bw/d, the highest dose level tested.

The corrected 8 hr inhalation NOAEC for workers is NOAEL * 1/0.38 * 6.7/10 (light exercise). Additionally a correction for differences between human and experimental exposure conditions of 1.4 is added (5 d/w versus experimental daily exposure): 8hr-NOAEC workers = NOAEL(50 mg/kg) * 1.76 * 1.4 = 123.4 mg/m3.

The suggested default factor of 2 to address uncertainty with respect to possible differences in absorption between inhalation and oral route has been not been applied based on the following considerations: Profiling information suggests a high oral absorption and QSAR estimates an uptake of 90%, and a higher absorption via inhalation is not realistic. Due to low vp, exposure is only possible as aerosol. If any exposure via inhalation does occur, this can only be in the form of larger droplets, as the use does not include fine spraying or mists. Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This result to no principal difference in absorption compared to oral route. And finally, Etheramine 10i has relative low systemic toxicity, and effects are characterized by local irritation first, which would limit substantial absorption via respiratory route.

AF for dose response relationship:
1
Justification:
Default (DNEL calculator). No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.7 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
70 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The substance has shown not to cause reproduction effects up to 50 mg/kg bw/d in an OECD 422 study covering the full developmental period. At this level some local irritation in the stomach was observed in the absence of systemic effects. A developmental toxicity study (OECD 414) in rats showed no developmental toxicity up to 75 mg/kg bw, at which level maternal toxicity consisted of local irritation in the stomach. In this case the DNEL for systemic toxicity is based in highest level tested in 90-day (OECD 408) study showing no local effects in stomach and showing no systemic toxicity at 50 mg/kg bw/d, the highest dose level tested. Extrapolation from oral NOAEL represents a worst case situation, as dermal absorption is considered to be lower compared to oral absorption. The dermal NOAEL for workers isadditionally corrected for differences between human and experimental exposure conditions with a factor of 1.4 (5 d/w versus experimental daily exposure): 8hr-NOAEC workers = NOAEL(50 mg/kg) * 1.4 = 70 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
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)

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:
0.74 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
37 mg/m³
Explanation for the modification of the dose descriptor starting point:

The substance has shown not to cause reproduction efects up to 50 mg/kg bw/d in an OECD 422 study covering the full developmental period. At this level some local irritation in the stomach was observed in the absence of systemic effects. A developmental toxicity study (OECD 414) in rats showed no developmental toxicity up to 75 mg/kg bw, at which level maternal toxicity consisted of local irritation in the stomach. In this case the DNEL for systemic toxicity is based in highest level tested in 90-day (OECD 408) study showing no local effects in stomach and showing no systemic toxicity at 50 mg/kg bw/d, the highest dose level tested.

The corrected 8 hr inhalation NOAEC for general population is NOAEL(50 mg/kg) * 1/1.35 (for 60 kg subject) mg/m3 = 37.0 mg/m3.

The suggested default factor of 2 to address uncertainty with respect to possible differences in absorption between inhalation and oral route has been not been applied based on the following considerations: Profiling information suggests a high oral absorption and QSAR estimates an uptake of 90%, and a higher absorption via inhalation is not realistic. Due to low vp, exposure is only possible as aerosol. If any exposure via inhalation does occur, this can only be in the form of larger droplets, as the use does not include fine spraying or mists. Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This result to no principal difference in absorption compared to oral route. And finally, Etheramine 10i has relative low systemic toxicity, and effects are characterized by local irritation first, which would limit substantial absorption via respiratory route

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
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:
hazard unknown but no further hazard information necessary as no exposure expected
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:
DNEL (Derived No Effect Level)
Value:
0.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
200
Dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The substance has shown not to cause reproduction effects up to 50 mg/kg bw/d in an OECD 422 study covering the full developmental period. At this level some local irritation in the stomach was observed in the absence of systemic effects. A developmental toxicity study (OECD 414) in rats showed no developmental toxicity up to 75 mg/kg bw, at which level maternal toxicity consisted of local irritation in the stomach. In this case the DNEL for systemic toxicity is based in highest level tested in 90-day (OECD 408) study showing no local effects in stomach and showing no systemic toxicity at 50 mg/kg bw/d, the highest dose level tested.Extrapolation from oral NOAEL represents a worst case situation, as dermal absorption is considered to be lower compared to oral absorption.

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
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:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
200
Dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The substance has shown not to cause reproduction efects up to 50 mg/kg bw/d in an OECD 422 study covering the full developmental period. At this level some local irritation in the stomach was observed in the absence of systemic effects. A developmental toxicity study (OECD 414) in rats showed no developmental toxicity up to 75 mg/kg bw, at which level maternal toxicity consisted of local irritation in the stomach. In this case the DNEL for systemic toxicity is based in highest level tested in 90-day (OECD 408) study showing no local effects in stomach and showing no systemic toxicity at 50 mg/kg bw/d, the highest dose level tested.

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
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 for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

No exposure of the general population to C10i-etheramine is foreseen based on the uses indicated in this dossier that are limited to industrial manufacture and formulation. Also assessment of indirect exposure is not needed as the tonnage is not above 1000 tpa, and the substance not is classified as CMR or toxic (R48 or STOT-RE).