N,N-dimethylglycinium chloride

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3 with logKow as the primary descriptor.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material : 2-(dimethylamino)acetic acid hydrochloride; N,N-dimethylglycinium chloride
- Molecular formula : C4H10ClNO2
- Molecular weight : 139.581 g/mol
- Smiles notation : OC(=O)CN(C)C.Cl
- InChl : 1S/C4H9NO2.ClH/c1-5(2)3-4(6)7;/h3H2,1-2H3,(H,6,7);1H
- Substance type: Organic
- Physical state: Solid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Raphidocelis subcapitata (previous names: Pseudokirchneriella subcapitata, Selenastrum capricornutum)

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Test temperature:

23.0 – 23.1 °C

pH:

8.01 – 9.26

Reference substance (positive control):

not specified

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

181.758 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((((((("a" or "b" or "c" or "d" or "e" )  and "f" )  and "g" )  and "h" )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and "s" )  and "t" )  and "u" )  and ("v" and ( not "w") )  )  and ("x" and "y" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aliphatic Amines AND Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Amine, tertiary OR Carboxylic acid OR No functional group found by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Amine, tertiary OR Carboxylic acid OR No functional group found OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid, aliphatic attach [-COOH] OR Alcohol, olefinic attach [-OH] OR Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Amino, aliphatic attach [-N<] OR Carbonyl, aliphatic attach [-C(=O)-] OR Miscellaneous sulfide (=S) or oxide (=O) OR No functional group found OR Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Amine OR Carbonic acid derivative OR Carboxylic acid OR Carboxylic acid derivative OR No functional group found OR Tertiary aliphatic amine OR Tertiary amine by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found AND SN1 AND SN1 >> Iminium Ion Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acid moiety AND Aliphatic Amines AND Inorganic Compound by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Alkoxy Silanes by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acid moiety AND Aliphatic Amines AND Inorganic Compound by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Amides OR Esters OR Esters (phosphate) by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Acid moiety AND Aliphatic Amines AND Inorganic Compound by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as SHOULD NOT BE PROFILED OR Thiols and Mercaptans by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Acid moiety AND Aliphatic Amines AND Inorganic Compound by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Salt by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Acid moiety AND Aliphatic Amines AND Inorganic Compound by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Neutral Organics by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Acid, aliphatic attach [-COOH] AND Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Amino, aliphatic attach [-N<] AND Carbonyl, aliphatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND No functional group found AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "u"

Similarity boundary:Target: Cl_CN(C)CC(O)=O
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Valproic acid (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.49

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.7

Validity criteria fulfilled:

not specified

Conclusions:

The median Effective concentration (EC50) value for 2-(dimethylamino)acetic acid hydrochloride on Pseudokirchneriella subcapitata in a 72 hour study was estimated to be 182 mg/L on the basis of effects on growth rate.

Executive summary:

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance 2-(dimethylamino)acetic acid hydrochloride (CAS no. 2491 -06 -7). EC50 value was estimated to be 182 mg/l for Pseudokirchneriella subcapitata for 72 h duration. Based on this value it can be concluded that the substance 2-(dimethylamino)acetic acid hydrochloride is considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

Description of key information

Using the OECD QSAR toolbox version 3.3 (2017) with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance2-(dimethylamino)acetic acid hydrochloride(CAS no. 2491 -06 -7). EC50 value was estimated to be 182 mg/l for Pseudokirchneriella subcapitata for 72 h duration. Based on this value it can be concluded that the substance2-(dimethylamino)acetic acid hydrochlorideis considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

Key value for chemical safety assessment

EC50 for freshwater algae:

182 mg/L

Additional information

Predicted data for the target chemical2-(dimethylamino)acetic acid hydrochloride (CAS No. 2491-06-7) and various supporting weight of evidence studies for its closest read across substances with logKow as the primary descriptorwere reviewed for toxicity to aquatic algae and cyanobacteria endpoint to summarize the following information:

 

Short term toxicity on aquatic algae and cyanobacteria of target chemical2-(dimethylamino)acetic acid hydrochloride (CAS No. 2491-06-7) is predicted using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances (2017).On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 182 mg/l for Pseudokirchneriella subcapitata for 72 duration. Based on this value it can be concluded that the substance2-(dimethylamino)acetic acid hydrochlorideis considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

 

In a weight of evidencestudy from authoritative database (J-CHECK, 2017) of the read across chemical 2,2-dimethyl propionic acid (CAS no. 75-98-9), short term toxicity to green algae study was carried out for 72 hrs. The study was performed according to OECD Guideline 201 (Alga, Growth Inhibition Test). The study was based on the effects of the read across compound 2,2-dimethyl propionic acid on green algae in a static fresh water system. Based on effect on growth rate of the test organism green algae, the 72 hr EC50 and NOEC value was determined to be 66 and 47 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance 2,2-dimethyl propionic acid can be considered as toxic to aquatic organisms. Since the chemical is readily biodegradable in nature, chemical 2,2-dimethyl propionic acid considered as non-toxic to aquatic organisms and thus can be considered to be not classified as per the CLP classification criteria.

 

Another short term toxicity to Selenastrum capricornutum (algae) study was carried out for 96 hrs (HSDB, 2017). The study was based on the effects of the read across compound 2,2-dimethyl propionic acid (CAS no. 75-98-9) on Selenastrum capricornutum in a static fresh water system at a temperature of 24 ± 2⁰C and pH of 7.4, respectively. Based on the effect on biomass of the test organism Selenastrum capricornutum, the 96 hr EC50 value was determined to be 75 mg/l. Thus, based on the EC50 value, it can be concluded that the substance 2,2 -dimethyl propionic acid can be considered as toxic to aquatic organisms. Since the chemical is readily biodegradable in nature, chemical 2,2 -dimethyl propionic acid considered as non-toxic to aquatic organisms and thus can be considered to be not classified as per the CLP classification criteria.

 

For the same read across chemical 2,2-dimethyl propionic acid (CAS no. 75-98-9) from secondary source (High Production Volume (HPV) Challenge Program; 2017),short term toxicity to Pseudokirchnerella subcapitata (green algae) study was carried out for 72 hrs. The study was performed according to OECD Guideline 201 (Alga, Growth Inhibition Test).The study was based on the effects of the read across compound 2,2-dimethyl propionic acid on Pseudokirchnerella subcapitata in a static fresh water system at a temperature of 23.4⁰C and pH of 7.1 – 7.6, respectively under continuous light. Test chemical concentrations used for the study were 62, 125, 250, 500 and 1000 mg/l (nominal concentrations) and 54.8, 128, 246, 488 and 979 mg/l (mean measured concentrations), respectively. The test material was not detected in the control. Individual test treatment solutions were prepared as Water Accommodated Fractions (WAFs). Test material was added to algal media in 2.0 L aspirator bottles. The vessels were mixed on magnetic stir plates with teflon coated stir bars for 23 hrs at room temperature. After mixing the solutions were allowed to settle for one hour and the aqueous portion of the WAF was removed from the bottom of the mixing vessel via the port and used for testing. Erlenmeyer flask with approximately 60 ml of treatment solution was inoculated with algae. Test vessels were sealed with foam stoppers. Four replicates were prepared for each treatment level. The initial algal density was 1.0 × 104cells/ml. All test replicates were placed on a shaker table at 100 oscillations per minute during the study. Samples were taken daily for cell counts. Biomass was calculated as the area under the growth curve. Test treatments were analyzed by GC-FID on Day 0 and at termination. Statistical analysis involves the use of Proc regression procedure of SAS, Anova procedure of SAS for NOEC. Based on effect on growth rate of the test organism Pseudokirchnerella subcapitata, the 72 hr EC50 and NOEC value was determined to be 979 and 246 mg/l, respectively and on the basis of biomass, the 72 hr EC50 and NOEC value was determined to be 878 and 246 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance 2,2-dimethyl propionic acid can be considered as non-toxic to aquatic organisms and thus can be considered to be not classified as per the CLP classification criteria.

 

Thus, based on the overall reported results for target chemical2-(dimethylamino)acetic acid hydrochloride(OECD QSAR toolbox version 3.3, 2017) and for its read across substance (fromauthoritative database J-CHECK, HSDB and secondary source),it can be concluded that the test substance2-(dimethylamino)acetic acid hydrochloridecan be considered as non-toxic to aquatic environment and can be considered to be notclassified as per the CLP classification criteria.