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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.2 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):
75
Dose descriptor starting point:
NOAEL
DNEL value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
88 mg/m³
Explanation for the modification of the dose descriptor starting point:

Based on the low molecular weight (102.2 g/mol), the high water solubility (>1000 g/l), and the moderate log Pow (-0.352 at 25°C)

it is assumed that oral absorption of the test substance is very high (R7c, ECHA, May 2008). Consequently, a default factor of 1 is included for route-to-route extrapolation, which means that 100% absorption is assumed for oral absorption, and 100% for inhalation.

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
1
Justification:
A higher assessment factor than 1 was not considered as reliable with regards to REACH guidance. Details see discussion.
AF for intraspecies differences:
5
Justification:
The intraspecies assessment factor of 5 was selected according to the REACH guidance. Details see discussion.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
2.5
Justification:
The approach used for DNEL derivation is conservative.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.2 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor:
other: corrected NOAEC from NOAEL (please compare with the long-term systemic DNEl delineation above)
DNEL value:
88 mg/m³
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
1
Justification:
A higher assessment factor than 1 was not considered as reliable with regards to REACH guidance. Details see discussion.
AF for intraspecies differences:
5
Justification:
The intraspecies assessment factor of 5 was selected according to the REACH guidance. Details see discussion.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
2.5
Justification:
The approach used for DNEL derivation is conservative.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA (2012). DNEL derivation will be reevaluated after availability of the additional studies currently performed with the read across substance DEAPA.

 

DNEL systemic long-term

No inhalation study is available for DMAPA CAS 109-55-7. Therefore, derivation of the DNEL has been based on the results from the available 28 day repeated dose toxicity study via oral application. It is also noted that effects observed by oral administration are likely to represent dominant local effects, for which route to route extrapolation is more uncertain than for clearly systemic effects. Therefore the approach and assessment factors as recommend in the ECHA guidance should be followed, as follows:

NOAEL 28 day study = 50 mg/kg bw day

Corrected starting point NOAEC inhalation = (50*6.7) /(0.38*10) = 88.2 mg/m3/d (ECHA Guidance on dose-response assessment, p21, allometric scaling is already included due to included respiratory rate differences)

AF interspecies: 2.5 (allometric scaling factor excluded, accounting for further interspecies uncertainties and exposure route extrapolation uncertainties)

AF intraspecies: 5 (workers, recommended also for local effects)

Time extrapolation: 6 (sub-acute to chronic, recommended also for local effects)

Total AF = 75

DNEL respiratory long term = 88 mg/m3 d / 75= 1.2 mg/m3 d (~ 0.3 ppm).

 

This DNEL is also appropriate considering Brubaker et al. 1979 (J Occuup Med 21(19), 688-90) indicating adverse effects on lung function in humans with 0.9 ppm, see above chapter “other effects”.

Considering the Brubaker reference where reduction of lung function was observed during one working shift at 0.9 ppm it is recommended to keep also the DNEL respiratory medium and acute term at the same level of 1.2 mg/m3 d (~ 0.3 ppm).

  

DNEL local long-term

The DNEL delineation as described under “Worker – Hazard via inhalation rout: systemic effects” is also thought to sufficiently protect from local irritation of the respiratory tract and especially resulting from single exposure already.

 

DNEL respiratory long term = 88 mg/m3 d / 75= 1.2 mg/m3 d (~ 0.3 ppm).

 

This DNEL is also appropriate considering Brubaker et al. 1979 (J Occup Med 21(19), 688-90) indicating adverse effects on lung function in humans with 0.9 ppm, see above chapter “other effects”. Considering the Brubaker reference where reduction of lung function was observed during one working shift at 0.9 ppm it is recommended to keep also the DNEL respiratory medium and acute term at the same level of 1.2 mg/m3 d (~ 0.3 ppm).

Moreover, in comparison with the German MAK commission established OELs for structurally related tertiary Alkylamines are between 1 and 2 ppm (e.g. 1 ppm for dimethylisopropylamine (CAS 996-35-0) and 2 ppm for triethylamine (CAS 121-44-8)), which are generally valid for systemic and local effects. It is therefore being assumed, that the long-term DNEL for systemic effects of 1.17 mg/m3 (0.22 ppm) is sufficiently conservative to also cover local effects. Therefore, as the derived DNEL for DMAPA is below the values of other comparable tertiary Alkylamines, it is considered to sufficiently low to protect from local effects of DMAPA representing a precautionary approach. This takes into account that DMAPA is structurally a diamine and considers the irritating effects on the respiratory tract already after a single exposure.

In addition, the DNEL for the close structural analogue DEAPA CAS 104-78-9 is much higher (=24.7 mg/m³). However, these data have been based on neutralized test material whereas DMAPA itself has bene tested as a free base (taking local properties into account, even after oral ingestion of the test substance). The DNEL for EDA CAS 107-15-3 is also much higher (=24 mg/m³). EDA is a respiratory sensitizer which has not been observed for DMAPA CAS 109-55-7. Therefore, the DMAPA-DNEL is considered to be sufficiently low to protect from single exposure respiratory irritation as well as from local toxicity with a high probability.

As a further comparison on a rather generic basis, in 2014 H. Messinger reported on“…An approach for the delineation of a generic cut-off value for local respiratory tract irritation by irritating or corrosive substances as a pragmatic tool to fulfill REACH requirements…”.As a result, it was shown in this publication that the OEL for irritating substances in this dataset is not lower than 10 mg/m3 and for corrosives not lower than1 mg/m3.“…Under certain conditions these generic limits could be applied as a pragmatic, but still sufficiently reliable and protective upper cut-off limit approach to avoid additional animal tests with irritating or corrosive chemicals.”

 

 

In conclusion, long term systemic & local inhalation DNEL, workers = 1.2 mg/m3

 

Acute/long term DNEL for local effects

 

Skin irritation/corrosion: The test substance is classified as irritating to the skin and appropriate qualitative risk managements should be implemented to avoid exposure. Thus, a qualitative risk assessment is done and the substance is assigned to the medium hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2012).

 

Eye irritation: The test substance is classified as irritating/sensitizing to the skin and appropriate qualitative risk managements should be implemented to avoid exposure. Thus, a qualitative risk assessment is done and the substance is assigned to the medium hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2012).

 

Respiratory irritation: The substance is classified as STOT SE cat. 3 (respriatory irritant). Thus, a qualitative risk assessment is done and the substance is assigned to the low hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2012).

 

Skin sensitisation:The test substance is classified as sensitizing (cat. 1B) to the skin and appropriate qualitative risk managements should be implemented to avoid exposure. Thus, a qualitative risk assessment is done and the substance is assigned to the medium hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2012).

References (not included as endpoint study record)

 

- ECHA (2012) Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health.Version 2.1 ECHA-2010 -G-19 –EN.

 

- ECHA (2016). Guidance on information requirements and chemical safety assessment. Chapter R.7a: Endpoint specific guidance

 

- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, November 2012.

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

General

General population is not intended tnor expected o be exposed to dimethylaminopropylamine (DMAPA) via oral, inhalation or dermal route. Therefore, no DNEL (long-term, inhalation and dermal exposure) is derived for general population. As TBPEH has no bioaccumulation potential no risk assessment for secondary poisoning is required for the general population.

 

References

(not included as endpoint study record)

 

- ECHA (2012) Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health.Version 2.1 ECHA-2010 -G-19 –EN.