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Toxicity to microorganisms

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activated sludge respiration inhibition testing
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
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.

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)).


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

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

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.

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
30 min
Dose descriptor:
Effect conc.:
> 1 000 mg/L

No respiration inhibition up to 1000 mg/L, the highest concentration tested

Conc.              Respiration
                       [mgO2/l*h]                  % of blank

Blank               17                               -

100 mg/L          19                               112

1000 mg/L        19                               112

A disturbance of sewage works in WWTP is not expected (EC20 > 100 mg/L).

Validity criteria fulfilled:
EC10 (30 min) > 1000 mg/L. The test is considered as valid.
Executive summary:

Activated domestic sludge was used to test the toxicity of diethylamine to aquatic microorganisms. This study can be used for the assessment of dimethylamine due to the similar chemical composition of both substances. The highest concentration tested was 1000 mg/L, whereby no respiration inhibition was investigated. An EC10 (30 min) >1000 mg/L is therefore reported as result of this study.

Description of key information

No data available for dimethylamine. Due to the fact that this endpoint is mandatory under REACH, a read-across to the chemical similar substance diethylamine (CAS 109-89-7) is done. The result of this study is used as key value for the CSA. EC10 (30 min) >1000 mg/L

Key value for chemical safety assessment

EC10 or NOEC for microorganisms:
1 000 mg/L

Additional information

No valid experimental data is available concerning the toxicity of dimethylamine to aquatic microorganisms. A read-across to diethylamine (CAS 109 -89 -7) is done for this endpoint. This is possible due to the similar chemical structure of both substances. The available data for diethylamine is reported as follows: Activated domestic sludge was used to test the toxicity to microorganisms of diethylamine. The highest concentration tested was 1000 mg/L, whereby no respiration inhibition was investigated. An EC10 (30 min) >1000 mg/L is therefore reported as result of this study. Furthermore, in a supporting study, Pseudomonas putida was exposed for 17 hour to diethylamine in an experiment according German Standard DIN 38412, Part 8. This study can also be used for the assessment of dimethylamine due to the similar chemical composition of both substances. The following results were reported: EC10 (17h) = 35 mg/L, EC50 (17h) = 47 mg/L, and EC90 (17h) = 60 mg/L, respectively.