Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.67 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):
18
Modified dose descriptor starting point:
NOAEC
Value:
264 mg/m³
Explanation for the modification of the dose descriptor starting point:
A 28-day repeated dose oral toxicity study with N-[3-(dimethylamino)propyl]-C18 unsaturated-alkylamide (unsaturated C18), conducted according to the OECD Guideline 407 and in compliance with GLP resulted to a systemic NOAEL of 150 mg/kg/day based on the absence of relevant findings in male and female Wistar rats up to 150 mg/kg bw/d. In addition, no local effects were observed. Starting point NOAEL of 150 mg/kg bw/d. The corrected 8h inhalation NOAEC for workers is (150 mg/kg)*1.76 mg/m3 = 264 mg/m3. No factor 2 route extrapolation from oral to inhalation was applied. Due to very low vp, 1.78 10-7 Pa at 25°C (EPI suite estimation), exposure is only possible as aerosol or larger particles as the use does not include fine spraying. Droplets will deposit mainly on upper airways and will be subsequently swallowed following mucocilliary transportation to pharynx. This results to no principal difference in absorption compared to oral route.
AF for dose response relationship:
1
Justification:
No specific concerns, starting from the NOAEL for systemic effects. In addition, no local response was observed.
AF for differences in duration of exposure:
6
Justification:
indicating by the guidance when extrapolation to subacute exosure to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
already included in NOAEC calculation
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5. Therefore a factor of 1 has been applied. The effects observed do not indicate a high uncertainty between species that will not be included in the allometric scaling
AF for intraspecies differences:
3
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intra-species differences for workers is 3 and not 5. As no relevant systemic effects have been identified and the only observed effects are interpreted as a local response following an non-specific mechanism with expected inherently relative low variation between individuals on the basis of possible specific sensitivities.
AF for the quality of the whole database:
1
Justification:
Available data derived from valid study showing consistent results with several studies.
AF for remaining uncertainties:
1
Justification:
No uncertainties identified
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 (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.08 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):
72
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
A 28-day repeated dose oral toxicity study with N-[3-(dimethylamino)propyl]-C18 unsaturated-alkylamide (unsaturated C18), conducted according to the OECD Guideline 407 and in compliance with GLP resulted to a systemic NOAEL of 150 mg/kg/day based on the absence of relevant findings in male and female Wistar rats up to 150 mg/kg bw/d. Starting point is extrapolated from this oral NOAEL which represents a worst case situation as dermal absorption is considered to be lower compared to oral absorption.
AF for dose response relationship:
1
Justification:
No specific concerns, starting from the NOAEL for systemic effects. In addition, no local response was observed.
AF for differences in duration of exposure:
6
Justification:
indicating by the guidance when extrapolating to subacute exposure to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
default factor for allometric scaling from rat to human
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review that there is no justification for the suggested addionional factor of 2.5. Therefore a factor of 1 has been applied. The effects observed do not indicate a high uncertainty between species that will not be included in the allometric scaling
AF for intraspecies differences:
3
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate factor for intra-species differences for workers is 3 and not 5. As the effects for which the risk assessment is made are secondary to a local response following a non-specific mechanism with expected inherently relative low variation between individuals, no additional factor is needed to accommodate for possible high uncertainty on the basis of possible specific sensitivities.
AF for the quality of the whole database:
1
Justification:
Available data derived from valid study showing consistent results with several studies.
AF for remaining uncertainties:
1
Justification:
No uncertainties identified
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:
no hazard identified
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:
no hazard identified
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

General Population - Hazard via oral 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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population