N,N-dimethylglycinium chloride

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

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):

Daphnia magna

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Hardness:

230 mg CaCO3/L

Test temperature:

20-21°C

pH:

Between 7.5 and 7.8 in the relevant test substance media and between 7.7 and 8.0 in the control media.

Dissolved oxygen:

8.2 - 9.6 mg O2/L

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

637.772 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

other: Intoxication

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

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

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> alpha,beta-carbonyl compounds with polarized multiple bonds OR High reactive >> Isothiazolinone derivatives by DPRA Cysteine peptide depletion

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 group OR Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "k"

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: "l"

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: "m"

Referential boundary: The target chemical should be classified as Esters OR Esters, Monothiophosphates by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "n"

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: "o"

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

Domain logical expression index: "p"

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: "q"

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

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Halogens AND Non-Metals by Groups of elements

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Alkali Earth OR Metalloids by Groups of elements

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 17 - Halogens Br OR Group 17 - Halogens I by Chemical elements

Domain logical expression index: "w"

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: "x"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.4

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.232

Validity criteria fulfilled:

not specified

Conclusions:

The median Effective concentration (EC50) value for 2-(dimethylamino)acetic acid hydrochloride on Daphnia magna in a 48 hour study was estimated to be 638 mg/L on the basis of effects on intoxication

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 invertebrates was predicted for target substance 2-(dimethylamino)acetic acid hydrochloride (CAS no. 2491 -06 -7). EC50 value was estimated to be 638 mg/l for Daphnia magna for 48 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 invertebrates was predicted for target substance 2-(dimethylamino)acetic acid hydrochloride (CAS no. 2491 -06 -7). EC50 value was estimated to be 638 mg/l for Daphnia magna for 48 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.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

638 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 to summarize the following information:

 

Short term toxicity on aquatic invertebrate 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 638 mg/l for Daphnia magna for 48 hr 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 peer reviewed journal (Tipton L. Randall et.al; 1980) of the read across chemical Carboxylic acid (CAS no. 64-18-6),short term toxicity to Daphnia magna study was carried out for 48 hrs. The study was based on the effects of the read across compound Carboxylic acid on Daphnia magnain a static fresh water system at a temperature of 22⁰C, pH7.7 with a water hardness of 154.5 mg/l as CaCO3, alkalinity of 137.7 mg/l as CaCO3, Ca/mg ratio of 32.7:19.7 mg/l, Na: 2.4 mg/l and K: 1.3 mg/l, respectively. The original stock of daphnia was obtained from the EPA laboratory in Duluth, Minn. Cultures of test organism have been maintained in EPA laboratory for about 2 years. Dilution water from a local spring fed pond was used as a culture media and for toxicity tests. First instar (12 ± 12 hours old) Daphnia were used for all tests. The tests were conducted in duplicate for 48 hrs at 22⁰C in a constant temperature chamber. Test chemical concentrations were nominal. The 48 hr EC50 value or toxic substance concentration that produces the effect of immobilization on 50% of the test populations after 48 hours, and their 95% confidence limits were determined. Based on effect on immobilization of the test organism Daphnia magna, the 48 hr EC50 value was determined to be 151.2 mg/l with a 95% C. I. of 138-165.6 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance Carboxylic 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.

 

Another short term toxicity to Artemia salina (Brine shrimp) study was carried out for 24 hrs for the same read across chemical Carboxylic acid (CAS no. 64-18-6) (Kenneth S. Price et. al; 1974). First range finding study was performed and then the study for determining the LC50 value was carried out. Test chemical concentration used for the range finding study were 100, 1000 and 10,000 mg/l and 100, 180, 320, 560 and 1000 mg/l, respectively for the determination of Tlm. The study was based on the effects of the read across compound Carboxylic acid on Artemia salina (12 mm in length) in a static fresh water system at a temperature of 24.5⁰C. For the range finding study, shrimp eggs were placed in the hatching device approx. 48 hrs in advance of the time that test shrimp would be required. After shrimp hatching was complete, the shrimp were collected and diluted to provide a suspension of shrimp with a titer of 30 to 50 shrimp/ml. Appropriate volume of a 1% solution of a chemical were placed 150 ml, wide mouth bottles. Artificial seawater was added to provide a total volume of 100 ml. The brine shrimp suspension (1 ml) was pipette into each bottles containing test chemical and into bottles containing only seawater (controls). The bottles were then loosely capped and incubated at ambient temperature of 24.5⁰C for 24 hrs. At the end of 24 hrs incubation period, the number of live and dead shrimp were noted by viewing the shrimp in the bottle aided by a colony counter. Brine shrimp have branch-like swimming appendages, phyllopodia, which also serve as gills. These appendages flutter very rapidly when the organism is healthy and the flutter rate decreases when the shrimp are distressed. No movement of the phyllopodia indicates death. Another sign of distress at near lethal concentrations was the clinging together of two or more shrimps. The result obtained in the screening tests were used to establish the dosage concentrations to be used for determining the TLm. By plotting the %survival versus the test dosage concentration, a straight line plot is obtained. The concentration at which this line cross 50% survival is reported as the Tlm. Based on effect on mortality of the test organism Artemia salina, the 24 hr LC50 value was determined to be 410 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance Carboxylic 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.

For the read across chemical 1,4-Butanedioic acid (CAS no. 110-15-6), short term toxicity to Daphnia magna study was carried out for 48 hrs (Tipton L. Randall et.al; 1980). The study was based on the effects of the read across compound 1,4-Butanedioic acid on Daphnia magna in a static fresh water system at a temperature of 22⁰C, pH7.7 with a water hardness of 154.5 mg/l as CaCO3, alkalinity of 137.7 mg/l as CaCO3, Ca/mg ratio of 32.7:19.7 mg/l, Na: 2.4 mg/l and K: 1.3 mg/l, respectively. The original stock of daphnia was obtained from the EPA laboratory in Duluth, Minn. Cultures of test organism have been maintained in EPA laboratory for about 2 years. Dilution water from a local spring fed pond was used as a culture media and for toxicity tests. First instar (12 ± 12 hours old) Daphnia were used for all tests. The tests were conducted in duplicate for 48 hrs at 22⁰Cin a constant temperature chamber. Test chemical concentrations were nominal. The 48 hr EC50 value or toxic substance concentration that produces the effect of immobilization on 50% of the test populations after 48 hours, and their 95% confidence limits were determined. Based on effect on immobilization of the test organism Daphnia magna, the 48 hr EC50 value was determined to be 374.2 mg/l with a 95% C. I. of 350-400 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance 1,4-Butanedioic 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.

 

In a supporting weight of evidence study from authoritative database (ECOTOX database; 2017) of the read across chemical 3-(N',N'-dimethylhydrazinecarbonyl)propanoic acid (CAS no. 1596-84-5),short term toxicity to Daphnia magna (Water flea) study was carried out for 48 hrs. The study was based on the effects of the test compound 3 -(N',N'-dimethylhydrazinecarbonyl) propanoic acid (CAS no. 1596 -84 -5) on Daphnia magna in a static fresh water system. Daphnia magna (Water flea) was used as a test organism. Based on effect on intoxication of the test organism Daphnia magna, the 48 hr EC50 value was determined to be 101 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance 3 -(N',N'-dimethylhydrazinecarbonyl)propanoic 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 ECOTOX and peer reviewed journals),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.