Dimethylamine

Long-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
In this justification, the read-across (bridging) concept is applied, based on the chemical structure of the potential analogues, their toxicokinetic behaviour and other available (eco-)toxicological data. Please refer also to the detailed read-across justification for ecotoxicological endpoints attached in section 13.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Dimethylamine and diethylamine belong to the group of secondary aliphatic amines with either two methyl or two ethyl groups attached to the central nitrogen atom (common structure / functional group).
The basicity of amines increases with the length of the aliphatic rest due to electron releasing properties of alkyl groups: the higher the pKa value, the weaker the acid, so the stronger the base. As such, diethylamine is more basic than dimethylamine.
The underlying hypothesis for the read-across is that the target and the source substance have similar properties due to structural similarity, resemblance to their chemical reactivity, and biotransformation products in environmental compartments. In other words, there is a clear chemical analogy (“common underlying mechanisms", scenario 2 of the Read Across Assessment Framework (ECHA 2017)).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)

source substance:
diethylamine
structural formula: C4H11N
SMILES: CCNCC
CAS 109-89-7
purity: not specified

target substance:
dimethylamine
structural formula: C2H7N
SMILES: CNC
CAS 124-40-3
purity: ≥ 99.9 %

3. ANALOGUE APPROACH JUSTIFICATION
Read across from the structural analogue to the target substance is based on the high structural similarity of the analogue with the substance of interest and the similarity of their (eco-) toxicological characteristics. Dimethylamine and diethylamine belong to the group of secondary aliphatic amines. In general, aliphatic amines undergo similar reactions and resemble each other in their physico-chemical properties. The fundamental properties of different amine classes (primary, secondary and tertiary) – basicity and nucleophilicity – are very much the same (Morrison and Boyd, 1987). Typical reactions of amines are salt formation, alkylation, and conversion into amides and Hofmann elimination from quaternary ammonium salts (Morrison and Boyd, 1987). Within this category the aquatic toxicity of aliphatic amines follows a regular pattern with regard to the carbon chain length. Furthermore, the chemicals are characterized by a common Mode Of Action (MOA) in detail as “narcotic amines” according to Acute aquatic toxicity MOA by OASIS in the OECD QSAR Toolbox v4.1.
The target and the source substances have an identical number of amines. The central nitrogen atom of the substances has an unshared electron pair that can accept a proton forming a substituted ammonium ion. Generally, secondary amines possess a more basic character than primary amines. The tendency to share this electron pair underlies the entire chemical behaviour of amines as a group and this was considered as main / basic parameter, which is suitable for read-across within an analogue approach within an/a analogue/category approach. They distinguish in the number of carbon atoms and thus in their molecular weight. With a molecular weight of 45.08 g/mol and a number of 2 carbon atoms, the target substance DMA (CAS 124-40-3) differs from the source substances DEA (CAS 111-75-1) (4 carbon atoms, 73.14 g/mol). Given the explanation above, stating that the toxicity of aliphatic amines grows with the number of carbons, the toxicity to aquatic organisms of the source substances can be interpolated to the target substance DMA < DEA.
DMA (gas) is legally classified as Skin Irrit. 2 and Eye Dam. 1, DMA (aqueous solution) is legally classified as Skin Corr. 1B; DMA-HCl has no legal classification.
The similar findings (refer to data matrix outlined below) for both substances support the conclusion that the substances will show a similar behaviour in the environmental compartment. Hence, DEA may serve as read-across substance for DMA. So, the available data on DEA can be used to cover all systemic endpoints currently lacking from DMA, making further testing obsolete.

4. DATA MATRIX
There is data available on the toxicological properties of DMA and DEA. Hence, the identification and discussion of common properties of DMA and DEA will be mainly based on this and physicochemical data.
The different physical state of the two substances (DMA is as a pure substance, gaseous at room temperature, DEA is a liquid) triggers some differences in the physico-chemical properties like melting point, boiling point, decomposition temperature and vapour pressure. Nevertheless, regarding the application of both substances, i.e. their distributed form, the gaseous character of DMA becomes less relevant as the substances are usually not applied in their pure forms but rather as aqueous solutions.
The available data for the following physico-chemical properties, which are relevant for absorption into living organisms, are very similar. Both substances are small molecules with a molecular weight of 45.0837 (DMA) resp. 73.14 (DEA), they are both very soluble in water (50 g/L at 20°C (DMA) and completely miscible in water (DEA)), have a low logPow (-0.274 (aqueous solution, 25°C, pH 10.8 - 11.1) (DMA) and 0.58 (DEA), vapour pressure values of 1688 hPa for DMA and 316 hPa for DEA were determined and are indicative for high to moderate volatility. Both are readily biodegradable. Although being expected to be hydrolytically stable in the natural environment, they both have a very low potential for bioaccumulation in aquatic and terrestrial organisms. The log Koc values are relatively close and as such the substances do not have a significant potential for persistence (not P not vP). DMA has a pKa of 10.73 at 20°C, DEA has a pKa of 11.09 at 20°C, which indicates that they exists almost entirely in the cationic form at pH values of 5 to 9.
DMA and DEA have a low toxicity potential and both do not have to be considered to be acutely harmful to fish, aquatic invertebrates nor to aquatic algae and cyanobacteria, nor to microorganisms. DMA is chronically toxic to fish (classification and labelling as Aquatic chronic 3). In view of the ready biodegradability of DMA the significance of this toxicity potential under real environmental conditions has to be judged carefully. For DEA no data on long-term toxicity to fish but data on long-term toxicity to aquatic invertebrates was available. The obtained NOEC(21d): 4.2 mg/L, and the LC50(21d): 5.7 mg/L show DEA not to be chronically toxic to aquatic invertebrates.

Reason / purpose for cross-reference:

read-across source

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

4.2 mg/L

Duration:

21 d

Dose descriptor:

LC50

Effect conc.:

5.7 mg/L

Validity criteria fulfilled:

yes

Conclusions:

NOEC = 4.2 mg/L, LC50 = 5.7 mg/L. The test is considered as valid since basic scientific principles are met.

Executive summary:

The structural analogue DEA (diethylamine, CAS No 109 -89 -7) was tested for long-term effects on Daphnia magna. Study was performed in accordance with OECD guideline 211 (Daphnia magna reproduction test), exposure period lasted 21 days. The test revealed the following results:

NOEC = 4.2 mg/L, LC50 = 5.7 mg/L.

These results can serve as data also for the target substance dimethylamine, which is expected to be as toxic as diethylamine.

Reference 2

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given

Principles of method if other than guideline:

30-d exposure of new born animals with monitoring of reproduction and mortality

GLP compliance:

no

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material: No surrogate or analogue material was used.

Analytical monitoring:

yes

Details on sampling:

No details available.

Vehicle:

no

Details on test solutions:

No details available.

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: waterflea
- Age: newborn (<= 24 h)
- Feeding during test
- Food type: green algae (Selenastrum)
- Amount: constant amounts
- Frequency: daily

Test type:

semi-static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

30 d

Post exposure observation period:

No post exposure observation period.

Hardness:

No details available.

Test temperature:

20 °C

pH:

No details available.

Dissolved oxygen:

No details available.

Salinity:

Not applicable.

Nominal and measured concentrations:

nominal: 0 (control), 1, 5, 10, 15 mg/L ds

Details on test conditions:

TEST SYSTEM
- Type: open
- Material, size, headspace, fill volume: 500 mL fill volume
- Renewal rate of test solution (frequency/flow rate): daily renewal
- No. of vessels per concentration: 25

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: standard water

OTHER TEST CONDITIONS
- Photoperiod: 16 h photoperiod

EFFECT PARAMETERS MEASURED:
fertility (number of newborn animals) and (number of dead animals): daily

RANGE-FINDING STUDY
- Test concentrations: 24-h LC50: 46 mg/L

Reference substance (positive control):

not specified

Duration:

30 d

Dose descriptor:

NOEC

Effect conc.:

10 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

act. ingr.

Basis for effect:

other: mortality and fertility

Details on results:

No details on results reported.

Results with reference substance (positive control):

Not applicable.

Reported statistics and error estimates:

No details available.

Validity criteria fulfilled:

not specified

Remarks:

Basic data given.

Conclusions:

No detailed study description available. NOEC(30d): 10 mg/L for Daphnia magna.

Executive summary:

The long-term toxicity to aquatic invertebrates was investigated over a 30 day expsosure period of newborn waterfleas (Daphnia magna) with monitoring on reproduction and mortality (Calamari, Galassi and Da Gasso, 1979). A semi-static test regime with daily renewal of the test solution was applied. The nominal test concentrations were 1, 5, 10 and 15 mg/L, beside a control of 0 mg/L. As result, a NOEC(30d) of 10 mg/L was reported.

Description of key information

RA: DEA (CAS 109-89-7): NOEC(21d): 4.2 mg/L, LC50(21d): 5.7 mg/L
DMA: NOEC(30d): 10 mg/L 

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

10 mg/L

Additional information

The structural analogue DEA (diethylamine, CAS No 109-89-7) was tested for long-term effects on Daphnia magna. Study was performed in accordance with OECD Guideline 211 (Daphnia magna reproduction test), exposure period lasted 21 days. The test revealed the following results: NOEC(21d): 4.2 mg/L, LC50(21d): 5.7 mg/L.

Concerning dimethylamine, the long-term toxicity to aquatic invertebrates was investigated over a 30 day exposure period of newborn waterfleas (Daphnia magna) with monitoring on reproduction and mortality (Calamari, Galassi and Da Gasso, 1979). A semi-static test regime with daily renewal of the test solution was applied. The nominal test concentrations were 1, 5, 10 and 15 mg/L, beside a control of 0 mg/L. As result, a NOEC(30d) of 10 mg/L was reported.