3-aminopropyldimethylamine

Toxicological Summary

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

Value:

50 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

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:

low hazard (no threshold derived)

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 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 recommended 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 information requirements and chemical safety assessment, R8). 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 chapter 7.10.5.

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 route: 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).

 

The derived DNEL for DMAPA is lower than the occupational exposure limit listed for Canada: 0,5 ppm (8 h shift). 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 been tested as a free base (taking local properties into account, even after oral ingestion of the test substance). 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 than 1 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.”

 

 

Qualitative risk assessment for acute local effects

 

Skin/eye corrosion, skin sensitisation, STOT SE (resp. irritant): The test substance is classified as STOT SE cat. 3 (respriatory irritant), corrosive to the skin/eyes and as skin sensitizer, 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).

 

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 nor expected to 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 DMAPA 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.