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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.76 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA defaults with incidental ECETOC modification
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Value:
17.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point is NOAEL 90-day rat  = 10 mg/kg bw/d for systemic toxicity. The corrected 8 hr inhalation NOAEC for workers is NOAEL (10 mg/kg) * 1.76 mg/m3 = 17.6  mg/m3.   No factor 2 route extrapolation from oral to inhalation. The substance is paste at room temperature with a low vapour pressure. Exposure via inhalation is only possible as aerosol of an aqueous solution. 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. Effects at LOAEL are not severe and only of local nature.
AF for differences in duration of exposure:
2
Justification:
Default for sub-chronic 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.
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Available data are derived from recent, high quality and valid studies showing consistent results.
AF for remaining uncertainties:
1
Justification:
Low severity of effects at LOAEL. Quality database: recent high quality studies.
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:
0.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECHA defaults with incidental ECETOC modification
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point is NOAEL 90-day rat  = 10 mg/kg bw/d for systemic toxicity.  No difference in absorption rates between dermal  and oral routes are taken into account. Value therefore represents an overestimation of the hazards.

AF for dose response relationship:
1
Justification:
No specific concerns. Effects at LOAEL are not severe and only of local nature.
AF for differences in duration of exposure:
2
Justification:
Default for sub-chronic 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, 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:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Available data are derived from recent, high quality and valid studies showing consistent results.
AF for remaining uncertainties:
1
Justification:
Low severity of effects at LOAEL. Quality database: recent high quality studies.
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)
Most sensitive endpoint:
skin irritation/corrosion
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

For the delineation of DNELs the following exposure patterns are considered: Since no consumer uses exist forN,N,N',N',N'-Pentamethyl-N-C16-18(even numbered)C18 unsatured-alkyl-1,3 propanediammonium chloride (common names:Diamine quaternised C16-18, C18 unsaturated), the only exposed population considered are workers which are expected to have infrequent and short-term exposures. However, for DNEL calculation chronic exposure conditions were assumed as worst-case scenario.

Selection of Assessment factors for Intra – Inter species variation for workers

 

ECHA (2008) has produced guidance on the assessment factors to use to derive a DNEL for human exposure based the application of assessment factors (safety factors) to an NOAEL or LOAEL in animal studies.

The guidance proposes that an assessment factor of 2 to be applied when extrapolating from an oral NOAEL to an inhalation DNEL. However in the case of fatty nitriles and the related derivatives, their low vapour pressure minimises the potential for generating vapour, and thus the risk of inhaling these materials in general. In the unlikely event that particulates are inhaled the relatively large particle size compared to inhalation of a vapour, would be expected to impinge on the nasal passages and the upper respiratory tract. This would result in the particulates being ingested rather than being absorbed after entering the deep lung. Therefore, based on the physico-chemical properties of these chemicals, an assessment factor of 1 will be applied when extrapolating from oral NOAEL values to inhalation DNELS.

The ECHA guidance proposes an assessment factor of 4 for the allometric scaling from rats to humans when calculating dermal DNELs. However it then proposes an additional factor of 2.5 to cover remaining differences (uncertainties) . There is no clear scientific justification for this additional factor. ECETOC in its Guidance on Assessment Factors to Derive DNELs (2010), reviewed the scientific evidence and concluded that the factor of 4 for rats was sufficient to cover the allometric scaling from rats to humans and any remaining differences are of intraspecies rather than interspecies variability. Based on this, the additional assessment factor of 2.5 for inter species variability will not be used.

This ECETOC guidance also reviewed the intraspecies assessment factors, which ECHA proposed as 5 for workers and 10 for the general population. ECETOC proposed in 2003, based on the scientific evidence, that assessment factors of 3 for workers and 5 for the general population are sufficient for covering any intraspecies variability, which includes the remaining differences factor of 2.5. A similar concept was developed for the German Auschuss für Gefahrstoffe -(2006), although arriving at a different factor. Apart from allometric scaling, taking interspecies differences for metabolism and toxicokinetics into account, a separate factor for overall (inter- and intra-species) variability for the workplace of 5 is taken. AGS explicitly did not differentiate between inter- and intra-species variability. 

After reviewing the three proposals, we have adopted the proposal from ECETOC as our default assessment factors. Where we have limited information or consider there to be the likelihood of addition intraspecies variation in response, then these factor may be increased for example as suggested by the German Auschuss für Gefahrstoffe of an assessment factor of 5 for workers.

To ensure any additional intra species variability is included in the ECETOC proposed assessment factor of 3 for workers will be increased by 2 to give a factor of 5, as described above following the approach of the AGS.

 

References:

ECETOC, 2010  Guidance on Assessment Factors to Derive DNELs,Technical Report XXX,ISSN-YYY,Final draft, March 17th2010

GermanAuschuss für Gefahrstoffe2006. Technische Regeln für Gefahrstoffe. Begründungen und Erläuterungen zu Grenzwerten in der Luft am Arbeitsplatz. Ausschuss für Gefahrstoffe. TRGS 901, BArbBl. Heft 1/2006.www.baua.de

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

N,N,N',N',N'-Pentamethyl-N-C16-18(even numbered)C18 unsatured-alkyl-1,3 propanediammonium chloride (common names:Diamine quaternised C16-18, C18 unsaturated,) is not used in the consumer sector.

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).