Ethyldimethylamine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

6.39 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Dose descriptor starting point:

NOAEC

Value:

318 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

160 mg/m³

Explanation for the modification of the dose descriptor starting point:

Modification for exposure conditions workers vs. experimental: NOAEC x 6,7m3/10m3 x 6h/8h

AF for dose response relationship:

1

Justification:

Default (DNEL calculator)

AF for differences in duration of exposure:

2

Justification:

Default (DNEL calculator)

AF for interspecies differences (allometric scaling):

1

Justification:

Default (DNEL calculator)

AF for other interspecies differences:

2.5

Justification:

Default (DNEL calculator)

AF for intraspecies differences:

5

Justification:

Default (DNEL calculator)

AF for the quality of the whole database:

1

Justification:

Default (DNEL calculator)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

20.4 mg/m³

Most sensitive endpoint:

acute toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

112.5

Dose descriptor starting point:

LOAEL

Value:

2 300 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

2 300 mg/m³

AF for dose response relationship:

3

Justification:

The starting point is an LD0 which is considered as a LOAEC for the systemic toxicity. With an assessment factor of 3, the derived NOAEC of 255 ppm is coherent with the effects observed at 500 ppm, but not at 100 ppm, during the first exposure day of the 7-day inhalation toxicity study.

AF for interspecies differences (allometric scaling):

1

Justification:

Default AF

AF for other interspecies differences:

2.5

Justification:

Default AF

AF for intraspecies differences:

5

Justification:

Default AF

AF for the quality of the whole database:

1

Justification:

Not needed

AF for remaining uncertainties:

3

Justification:

The NOAEC is only related to mortality and clinical signs and not based on a full toxicological evaluation.

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.4 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

12.5

Dose descriptor:

NOAEC

Value:

30 mg/m³

AF for dose response relationship:

1

Justification:

Not needed

AF for differences in duration of exposure:

1

Justification:

The nasal irritation is not duration-related but driven but the concentration. The NOAECs for local nasal effects are consistent between the 28- and the 90-day inhalation exposure (Van Triel 2019 and Beebe, 2021, respectively) are set at 10 ppm and used for risk assessment.

AF for interspecies differences (allometric scaling):

1

Justification:

Not needed

AF for other interspecies differences:

2.5

Justification:

Default AF

AF for intraspecies differences:

5

Justification:

Default AF

AF for the quality of the whole database:

1

Justification:

Not needed

AF for remaining uncertainties:

1

Justification:

Not needed

Acute/short term exposure

Hazard assessment conclusion:

other toxicological threshold

Value:

15 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

9.22 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Dose descriptor starting point:

NOAEC

Value:

318 mg/m³

Modified dose descriptor starting point:

NOAEL

Value:

922.2 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

DNEL derivation is based on a 90-day toxicity study by inhalation administration to rats (Beebe, 2021). The starting dose for DNEL calculation is a NOAEC of 318 mg/m3 (106 ppm). Considering a ventilation rate of 0.29 m3/kg for a 6-hour exposure and a default inhalation absorption of 100%, the corresponding internal NOAEL is 92.22 mg/kg bw/d. DMEA is expected to be poorly absorbed by the skin (10% of the dose), therefore the dermal NAEL derived for workers is 922.2 mg/kg bw/d.

 

AF for dose response relationship:

1

Justification:

Default (DNEL calculator)

AF for differences in duration of exposure:

2

Justification:

Default (DNEL calculator)

AF for interspecies differences (allometric scaling):

4

Justification:

Default (DNEL calculator)

AF for other interspecies differences:

2.5

Justification:

Default (DNEL calculator)

AF for intraspecies differences:

5

Justification:

Default (DNEL calculator)

AF for the quality of the whole database:

1

Justification:

Default (DNEL calculator)

AF for remaining uncertainties:

1

Justification:

Default (DNEL calculator)

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - workers

Occupational exposure limits (OEL) are in force in different EU countries for dimethylethylamine (DMEA) (Gestis data base, consulted on 26/07/2019)

 

	Limit value - Eight hours		Limit value - Short term
	ppm	mg/m³	ppm	mg/m³
Denmark	5	15	10	30
Finland	5	15	10 (1)	30 (1)
France	5	15	25	75
Germany (DFG)	2	6,1	5 (2)	15 (2)
Ireland	10	30	15 (1)	45 (1)
Spain	25	75	50	150
Sweden	2	6	5 (1)	15 (1)
Switzerland	2	6,1	4	12,2
United Kingdom	10	30	15	46

(1) 15 minutes average value

(2) Ceiling limit value

 

According to Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, a registrant cannot use a national OEL in place of a DNEL without an evaluation of the scientific background for setting the national OEL. However, in cases where toxicological information and evaluations of health effects used for setting the national OEL are documented and available, this may, as for IOELs, be used and taken into account in deriving the DNEL. In this evaluation, the approach used for setting the national OEL should be compared to the approach for deriving DNELs as described in the in the main body of this chapter, and any differences in approach should be taken into account.

 

According to the German MAK documentation (2000), critical effects of N, N-dimethylethylamine in humans are visual disturbances. A study in humans difficultly evaluable showed after a single 8-hour exposure at 3.3 ml/m3 (10 mg/m3) a slight corneal swelling, but no visual disturbances.

 

At the workplace N, N-dimethylethylamine concentration from 3.3-4.4 ml/m3 (10.0 to 13.2 m/m3, 8-hour average) led to visual disturbance. Irritation of eyes, nose and throat occurred from 8 rnl/m3. The authors of this study derived a NOEL of 3 ml/m3 (from 10 mg/m3) (Warren and Selchan 1988). In volunteers (Stahlbom et al., 1991), a 15-minute exposure to 33-50 ml/m3 (100-165 mg/m3) caused irritation but no visual disturbances. These conflicting result after single and chronic exposure may indicate that the visual disturbances are dependent on the exposition duration not only to peaks of exposure, and that chronically exposed people reacts more sensitively to the substance. The study, in which at 0.4 to 0.8 ml of N, N-dimethylethylamine/m3 (1.2 to 2.4 mg/m3) were already observed headaches, irritation to eyes and nasal mucosa, impaired vision, dizziness and nausea, may be due to a mixed exposure, was not used for evaluation. The current MAK (2018) is equal to 2 ml/m3 (6.07 mg/m3). Since with a double concentration of short- term duration the irritation is not so intensive, the peak limit fells to Category I with a short-term exceeding factor of 2.

 

 

 

N, N-dimethylethylamine was not sensitizing in the guinea pig maximization test and will not therefore, S 'marked. Since systemic effects after percutaneous exposure is not so far proven, currently a mark with "H" is not justified.

 

In foundries in nuclear core-production by the cold-box process, personal and indoor air measurements have demonstrated the formation of nitrosamines N-nitrosodimethylamine and N-Nitrosoethylmethylamine from the N, N-Dimethylethylamine (Ducos et al. 1988), N,N- dimethylethylamine is labelled with the footnote, reaction with nitrosating agents can lead to the formation of carcinogenic N-nitrosodimethylamine and N-Nitrosoethylmethylamine, see Chapter III. Formation of carcinogenic amines by nitrosation.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.14 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Dose descriptor starting point:

NOAEC

Value:

318 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

57.2 mg/m³

Explanation for the modification of the dose descriptor starting point:

Modification for exposure conditions general population vs. experimental: NOAEC x 6h/24h x 5d/7d

AF for dose response relationship:

1

Justification:

Default (DNEL calculator)

AF for differences in duration of exposure:

2

Justification:

Default (DNEL calculator)

AF for interspecies differences (allometric scaling):

1

Justification:

Default (DNEL calculator)

AF for other interspecies differences:

2.5

Justification:

Default (DNEL calculator)

AF for intraspecies differences:

10

Justification:

Default (DNEL calculator)

AF for the quality of the whole database:

1

Justification:

Default (DNEL calculator)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

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):

25

Dose descriptor:

NOAEC

Value:

30 mg/m³

AF for dose response relationship:

1

Justification:

Not needed

AF for differences in duration of exposure:

1

Justification:

The nasal irritation is not duration-related but driven but the concentration. The NOAEC are consistent between the 28- and the 90-day inhalation exposure and are set at 10 ppm. The NOAEC of 10 ppm (30 mg/m") is used for risk assessment.

AF for interspecies differences (allometric scaling):

1

Justification:

Not needed

AF for other interspecies differences:

2.5

Justification:

Default AF

AF for intraspecies differences:

10

Justification:

Default AF

AF for the quality of the whole database:

1

Justification:

Not needed

AF for remaining uncertainties:

1

Justification:

Not needed

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.3 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

200

Dose descriptor starting point:

NOAEC

Value:

318 mg/m³

Modified dose descriptor starting point:

NOAEL

Value:

658 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

DNEL derivation is based on a 90-day toxicity study by inhalation administration to rats (Beebe, 2021). The starting dose for DNEL calculation is a NOAEC of 318 mg/m3 (106 ppm). Considering a ventilation rate of 0.29 m3/kg for a 6-hour exposure of rats and a default inhalation absorption of 100%, the corresponding internal NOAEL is 92.22 mg/kg bw/d. DMEA is expected to be poorly absorbed by the skin (10% of the dose), therefore the dermal NAEL derived for general populations after adjustment for exposure duration (7 days/week) is 658 mg/kg bw/d.

 

AF for dose response relationship:

1

Justification:

Default (DNEL calculator)

AF for differences in duration of exposure:

2

Justification:

Default (DNEL calculator)

AF for interspecies differences (allometric scaling):

4

Justification:

Default (DNEL calculator)

AF for other interspecies differences:

2.5

Justification:

Default (DNEL calculator)

AF for intraspecies differences:

10

Justification:

Default (DNEL calculator)

AF for the quality of the whole database:

1

Justification:

Default (DNEL calculator)

AF for remaining uncertainties:

1

Justification:

Not needed

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.33 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

200

Dose descriptor starting point:

NOAEC

Value:

318 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

65.8 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

DNEL derivation is based on a 90-day toxicity study by inhalation administration to rats (Beebe, 2019). The starting dose for DNEL calculation is a NOAEC of 318 mg/m3 (106 ppm). Considering a ventilation rate of 0.29 m3/kg for a 6-hour exposure of rats and a default inhalation absorption of 100%, the corresponding internal NOAEL is 92.22 mg/kg bw/d. DMEA is expected to be readily absorbed by the GI tract (100% of the dose), therefore the oral NAEL derived for general populations after adjustment for exposure duration (7 days/week) is 65.8 mg/kg bw/d.

 

AF for dose response relationship:

1

Justification:

Default (DNEL calculator)

AF for differences in duration of exposure:

2

Justification:

Default (DNEL calculator)

AF for interspecies differences (allometric scaling):

4

Justification:

Default (DNEL calculator)

AF for other interspecies differences:

2.5

Justification:

Default (DNEL calculator)

AF for intraspecies differences:

10

Justification:

Default (DNEL calculator)

AF for the quality of the whole database:

1

Justification:

Default (DNEL calculator)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)