Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.9 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):
18
Dose descriptor starting point:
NOAEL
Value:
3.25 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
16.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for the registered substance (see discussion) which is based upon cross-reading from the 28-day study on (Z)-octadec-9 –enylamine resulting to a NOAEL of 3.25 mg/kg bw/day. This is then converted to the corresponding value of the salt, resulting to a NOAEL of about 9.2 mg/kg bw/day: Mw oleylamine = 267.5, MW salt = 757 ; 3.25 x 757/267.5 = 9.2 mg/kg bw/day From this follows for the corrected 8 hr inhalation NOAEC for workers (9.2 mg/kg) * 1.76 mg/m3= 16.2 mg/m3. No factor 2 for route extrapolation from oral to inhalationis applied. Due to very low vp (10-6), significant exposure is only possible as aerosol. If any inhalation does occur, this can only be in the form of larger droplets, as the use does not include fine spraying. Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This results to no principal difference in absorption compared oral route.

AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL, effects at LOAEL are not severe and of local nature.
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for subacute 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 for this, therefore a factor of 1 has been applied. As effects are interpreted as being local and related to the route of exposure (see comments), the already applied allometric scaling already represents a worst case.
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 the effects for which the risk assessment is made is based on a local response following an non-specific mechanism with expected inherently relative low variation between individuals, no additional factor is needed to accommodate for possible high uncertainty between individuals on the basis of possible specific sensitivities.
AF for the quality of the whole database:
1
Justification:
Available data derived from valid studies showing consistent results within category.
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:
no hazard identified
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:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
72
Dose descriptor starting point:
NOAEL
Value:
3.25 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
15.33 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for the registered substance (see discussion) which is based upon cross-reading from the 28-day study on (Z)-octadec-9 –enylamine resulting to a NOAEL of 3.25 mg/kg bw/day. This is then converted to the corresponding value of the salt, resulting to a NOAEL of about 9.2 mg/kg bw/day: Mw oleylamine = 267.5, MW salt = 757 ; 3.25 x 757/267.5 = 9.2 mg/kg bw/day. A dermal rate has been established to be 60 % dermal absorption may be taken as a worst case for assessment purposes (value taken from the existing EU risk assessment on primary alkylamines) leading to a dermal NOAEL of 15.33 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL, effects at LOAEL are not severe and of local nature.
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for subacute 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 additional factor of 2.5 for this, therefore a factor of 1 has been applied. As effects are interpreted as being local related to the route of exposure, the applied allometric scaling already represents a worst case
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 the effects for which the risk assessment is made is based on a local response following an non-specific mechanism with expected inherently relative low variation between individuals, no additional factor is needed to accommodate for possible high uncertainty between individuals on the basis of possible specific sensitivities.
AF for the quality of the whole database:
1
Justification:
Available data derived from valid studies showing consistent results within category.
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:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.19 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):
42
Dose descriptor starting point:
NOAEL
Value:
3.25 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
8 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for the registered substance (see discussion) which is based upon cross-reading from the 28-day study on (Z)-octadec-9 –enylamine resulting to a NOAEL of 3.25 mg/kg bw/day. This is then converted to the corresponding value of the salt, resulting to a NOAEL of about 9.2 mg/kg bw/day: Mw oleylamine = 267.5, MW salt = 757 ; 3.25 x 757/267.5 = 9.2 mg/kg bw/day From this follows for the corrected 8 hr inhalation NOAEC for workers (9.2 mg/kg) * 1/1.15 mg/m3 = 8 mg/m3. No factor 2 for route extrapolation from oral to inhalation is applied. Due to neglectable vp (<< 10-6 Pa) , significant exposure is only possible as aerosol. If any inhalation does occur, this can only be in the form of larger droplets, as the use does not include fine spraying. Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This results to no principal difference in absorption compared oral route.

AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL, effects at LOAEL are not severe and of local nature.
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for subacute to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC
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 for this, therefore a factor of 1 has been applied. As effects are interpreted as being local and related to the route of exposure (see comments), the already applied allometric scaling already represents a worst case.
AF for intraspecies differences:
7
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intraspecies differences for general public is 5 and not 10, In this case the factor 7 is used to accommodate for the possible high uncertainty between individuals as the effects for which the risk assessment is made possibly includes a local response.
AF for the quality of the whole database:
1
Justification:
Available data derived from valid studies showing consistent results within category.
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:
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:
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):
168
Dose descriptor starting point:
NOAEL
Value:
3.25 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
15.33 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for the registered substance (see discussion) which is based upon cross-reading from the 28-day study on (Z)-octadec-9 –enylamine resulting to a NOAEL of 3.25 mg/kg bw/day. This is then converted to the corresponding value of the salt, resulting to a NOAEL of about 9.2 mg/kg bw/day: Mw oleylamine = 267.5, MW salt = 757 ; 3.25 x 757/267.5 = 9.2 mg/kg bw/day. A dermal rate has been established to be 60 % dermal absorption may be taken as a worst case for assessment purposes (value taken from the existing EU risk assessment on primary alkylamines) leading to a NOAEL dermal of 15.33 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL, effects at LOAEL are not severe and of local nature.
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for subacute 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 additional factor of 2.5 for this, therefore a factor of 1 has been applied. As effects are interpreted as being local related to the route of exposure, the applied allometric scaling already represents a worst case
AF for intraspecies differences:
7
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 the effects for which the risk assessment is made is based on a local response following an non-specific mechanism with expected inherently relative low variation between individuals, no additional factor is needed to accommodate for possible high uncertainty between individuals on the basis of possible specific sensitivities.
AF for the quality of the whole database:
1
Justification:
Available data derived from valid studies showing consistent results within category.
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:
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:
DNEL (Derived No Effect Level)
Value:
0.05 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):
168
Dose descriptor starting point:
NOAEL
Value:
3.25 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
9.2 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for the registered substance (see discussion) which is based upon cross-reading from the 28-day study on (Z)-octadec-9 –enylamine resulting to a NOAEL of 3.25 mg/kg bw/day. This is then converted to the corresponding value of the salt, resulting to a NOAEL of about 9.2 mg/kg bw/day: Mw oleylamine = 267.5, MW salt = 757 ; 3.25 x 757/267.5 = 9.2 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL, effects at LOAEL are not severe and of local nature.
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for subacute 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 additional factor of 2.5 for this, therefore a factor of 1 has been applied. As effects are interpreted as being local related to the route of exposure, the applied allometric scaling already represents a worst case.
AF for intraspecies differences:
7
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intraspecies differences for general public is 5 and not 10, In this case the factor 7 is used to accommodate for the possible high uncertainty between individuals as the effects for which the risk assessment is made possibly includes a local response.
AF for the quality of the whole database:
1
Justification:
Available data derived from valid studies showing consistent results within category.
AF for remaining uncertainties:
1
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

No exposure of the general population to the registered substance based on the uses indicated in this dossier that are limited to industrial manufacture and formulation.

However, to allow for evaluation from indirect exposures via the environment, DNELs have been derived for systemic toxicity from long term exposures via all routes.