3,4-dimethoxyphenethylamine

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:

QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- IUPAC name: 2-(3,4-dimethoxyphenyl)ethan-1-amine
- Common name: 3,4-dimethoxyphenethylamine
- Molecular weight: 181.2335 g/mole
- Molecular formula: C10H15NO2
- Smiles: COc1ccc(CCN)cc1OC
- Inchl: 1S/C10H15NO2/c1-12-9-4-3-8(5-6-11)7-10(9)13-2/h3-4,7H,5-6,11H2,1-2H3
- Physical state: Liquid
- Substance type: Organic

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

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

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Test temperature:

23.9-24.5°C

pH:

7.8 to 8.0

Reference substance (positive control):

not specified

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

367.301 mg/L

Nominal / measured:

estimated

Conc. based on:

not specified

Basis for effect:

growth rate

Remarks on result:

other: Other details not known

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 5 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 ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and ("u" and "v" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Primary amines by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Amines by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Michael addition AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Narcotic Amine by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m OR (!Undefined)Group CNS Surface Tension > 62 mN/m OR Exclusion rules not met OR Group All log Kow < -3.1 OR Group All Melting Point > 200 C OR Group C Melting Point > 55 C OR Group CN Aqueous Solubility < 0.0001 g/L OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol OR Group CN Vapour Pressure < 0.001 Pa OR Group CNS log Kow < 0.5 OR Group CNS Melting Point > 120 C OR Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as 1,3-dialkoxy-benzene OR alpha,beta-unsaturated aliphatic alkoxy group OR Epoxides and aziridines OR No alert found OR Primary aromatic amine, hydroxyl amine and its derived esters OR Simple aldehyde by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aliphatic amine   [-NH2  or  -NH-] AND Alkyl substituent on aromatic ring AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-CH2 AND Aromatic-H AND Benzene AND -CH2-  [linear] AND Methyl  [-CH3] by Bioaccumulation - metabolism alerts

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aliphatic alcohol  [-OH] by Bioaccumulation - metabolism alerts

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aliphatic amine   [-NH2  or  -NH-] AND Alkyl substituent on aromatic ring AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-CH2 AND Aromatic-H AND Benzene AND -CH2-  [linear] AND Methyl  [-CH3] by Bioaccumulation - metabolism alerts

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aliphatic ether  [C-O-C] by Bioaccumulation - metabolism alerts

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aliphatic amine   [-NH2  or  -NH-] AND Alkyl substituent on aromatic ring AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-CH2 AND Aromatic-H AND Benzene AND -CH2-  [linear] AND Methyl  [-CH3] by Bioaccumulation - metabolism alerts

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as -CH2-  [cyclic] by Bioaccumulation - metabolism alerts

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Aliphatic amine   [-NH2  or  -NH-] AND Alkyl substituent on aromatic ring AND Aromatic ether  [-O-aromatic carbon] AND Aromatic-CH2 AND Aromatic-H AND Benzene AND -CH2-  [linear] AND Methyl  [-CH3] by Bioaccumulation - metabolism alerts

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Urea   [N-C(=O)-N] by Bioaccumulation - metabolism alerts

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.428

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.85

Validity criteria fulfilled:

not specified

Conclusions:

Based on the growth rate inhibition of algae Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) by the chemical 2-(3,4-dimethoxyphenyl)ethan-1 -amine, the EC50 was estimated to be 367.3 mg/l.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the four closest read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for 2-(3,4-dimethoxyphenyl)ethan-1-amine (120-20-7). Based on the growth rate inhibition of algae Pseudokirchneriella subcapitata by the chemical 2-(3,4-dimethoxyphenyl)ethan-1 -amine, the EC50 was estimated to be 367.3 mg/l. Based on this value it can be concluded that the substance 2-(3,4-dimethoxyphenyl)ethan-1-amine (120-20-7) is considered be nontoxic to aquatic environment and cannot be classified as per the criteria mentioned in CLP regulation.    

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the four closest read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for 2-(3,4-dimethoxyphenyl)ethan-1-amine (120-20-7). Based on the growth rate inhibition of algae Pseudokirchneriella subcapitata by the chemical 2-(3,4-dimethoxyphenyl)ethan-1 -amine, the EC50 was estimated to be 367.3 mg/l. Based on this value it can be concluded that the substance 2-(3,4-dimethoxyphenyl)ethan-1-amine (120-20-7) is considered be nontoxic to aquatic environment and cannot be classified as per the criteria mentioned in CLP regulation.    

Key value for chemical safety assessment

EC50 for freshwater algae:

367.3 mg/L

Additional information

Based on the various predicted data for the target chemical and experimental data for structurally and functionally similar read across chemicals study have been reviewed to determine the toxic nature of target chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine (120-20-7) on the growth of algae. The studies are as mentioned below:   

 

The first predicted study for the target chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine (120-20-7) from SSS QSAR using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the four closest read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for 2-(3,4-dimethoxyphenyl)ethan-1-amine (120-20-7). Based on the growth rate inhibition of algae Pseudokirchneriella subcapitata by the chemical 2-(3,4-dimethoxyphenyl)ethan-1 -amine, the EC50 was estimated to be 367.3 mg/l. Based on this value it can be concluded that the substance 2-(3,4-dimethoxyphenyl)ethan-1-amine (120-20-7) is considered be nontoxic to aquatic environment and cannot be classified as per the criteria mentioned in CLP regulation.    

 

Similarly in the second weight of evidence study for the 2-(3,4-dimethoxyphenyl)ethan-1-amine (120-20-7) prediction done using the EPI Suite ECOSAR version 1.11, the short term toxicity on green algae was predicted for test substance 2-(3,4-dimethoxyphenyl)ethan-1-amine (120 -20 -7). On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 318.6 mg/l for green algae for 72 hrs duration. Based on this value, it can be concluded that the test chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine (120 -20 -7) can be considered as non-toxic to green algae at environmentally relevant concentrations and can be considered not-classified as per the CLP classification criteria.

 

First predicted study was supported by the second experimental weight of evidence study for the read across chemical 4-methoxyphenylacetic acid (104-01-8) from ABITEC report. The freshwater algal growth inhibition test was carried out on Desmodesmus subspicatus with the substance 4-methoxyphenylacetic acid (CAS No.- 104 -01 -8) according to OECD Guideline 201. The stock solution 150.0 mg/L was prepared by dissolving white powder in OECD growth medium. Test solutions of required concentrations were prepared by mixing the stock solution of the test sample with OECD growth medium and inoculum culture and tested at the concentrations 0, 0, 30.0, 45.0, 67.5, 100.0 and 150.0 mg/L. Effects on the growth rate of the organism were studied. The test was performed under static conditions in a static fresh water system at a temperature of 23± 2°C. Initial cell density of test organism used was 5x10(3) cells/ml. Determination of cell counting involve the use of microscope with counting chamber Cyrus I or electronic particle counter. ErC50 was calculated using non-linear regression by the software Prism 4.0. The median effective concentration (ErC50) for the test substance, 4-methoxyphenylacetic acid, in a freshwater algae Desmodesmus subspicatus was determined to be 106.9 mg/L on the basis of effects on growth rate in a 72 hour study with 95% Cl of 83.2 - 137.3 mg/L. Thus, based on this ErC50 value and according to CLP Criteria for aquatic classification of the substance, it is concluded that 4-methoxyphenylacetic acid (CAS No: 104 -01 -8) does not exhibits toxicity to aquatic algae (Desmodesmus subspicatus).

 

Similarly for the same read across chemical 4-methoxyphenylacetic acid (104-01-8) from UERL, the effect of test item 4-methoxyphenylacetic acid, CAS No. 104-01-8 was studied on the growth of fresh water green alga Chlorella vulgaris. The study was conducted following OECD guideline 201- Alga, growth inhibition test. The test concentration chosen for the study were 0.9 mg/L,2.7 mg/L,8.1 mg/L,24.3 mg/L,72.9 mg/L,218.7 mg/L. The test concentrations were prepared using stock solution of the test item using mineral media. The green alga was exposed to the test concentration for a period of 72 hours to observe average specific growth rate and % growth inhibition under the effect of the test item. EC50 calculated graphically through probit analysis was observed to be >200 mg/L. Thus, based on this EC50 value and according to CLP Criteria for aquatic classification of the substance, it is concluded that 4-methoxyphenylacetic acid (CAS No 104 -01 -8) does not exhibits toxicity to aquatic algae (Chlorella vulgaris).

 

 The fifth study was conducted on the structurally and functionally similar read across chemicals (105-15-3) from UERL lab report. This study was designed to assess the toxic effects of the test compound 4-methoxyphenyl)methanol (105 -13 -5) on the growth of green alga Chlorella vulgaris. The study was conducted following OECD guideline 201- Alga, growth inhibition test. The test concentration chosen for the study were 6.25mg/l, 12.5mg/l, 25mg/l, 50mg/l, 100mg/l and 200mg/l. All the tests were carried out in 100mL conical flasks which were carefully autoclaved and sterilized. The test solution in each of these test vessels was kept constant which is 60 ml so that a sufficient amount of head space was left. The test solution was prepared in aseptic condition. The test substance 4-methoxybenzyl alcohol was prepared by adding 60 µl of test substance in 300 ml of BBM to get the final concentration of 200 mg/L. The remaining test solutions were prepared by dilution from the above stock solution. To have a better growth and visibility of cells, the initial cell density of the culture was kept 1 X 104 cells/ml. Care was taken to have a homogeneous solution for the experiment. For the assessment of algal growth, the test was conducted in replicates. The control flask was maintained in triplicates as recommended in the OECD guideline and the test concentration were selected in geometric series which were maintained in duplicates. To obtain a quantitative concentration-response relationship by regression analysis, a linearizing transformation of the response data into probit was performed. Using the same, effective concentration (EC) were determined. After 72 hours of exposure to test item 4-methoxyphenyl) methanol to various nominal test concentrations, EC50 was determine to be >200mg/l and the EC10 was determine to be 158.49 mg/l graphically and through probit analysis. Based on the EC50, it can be consider that the chemical was nontoxic and can be consider to be not classified as per the CLP classification criteria.

 

Similarly for another read across chemical (738-70-5) from peer reviewed journal (Chemosphere, 2014) determination of short term toxicity of chemical 2,4-Diamino-5-(3,4,5-trimethoxybenzyl)- pyrimidin (Trimethoprim) on the growth of aquatic algae Pseudokirchneriella subcapitata CCAP 278/4 for 72hrs. Green algae were cultivated and tested in the OECD TG 201 medium and in the growth medium BG 11. Test performed in 250 ml Erlenmeyer flasks filled with 100 mL of the test medium. 3 replicates were used in the test. After the exposure of chemical for 72hrs, the ErC10 was 65 mg/l with the 95% CI of 0.01-103 mg/l and the ErC50 was 129 mg/l with 95% CI 123-136 mg/l. Based on the growth inhibition of Selenastrum capricornutum CCAP 278/4, due to the exposure of chemical, the ErC50 was 129 mg/l with 95% CI 123-136 mg/l. Based on the ErC50, it is concluded that the chemical was nontoxic and can be consider to be not classified as toxic to aquatic environment as per the CLP classification criteria.

 

Based on the predicted data for the target chemical (from OECD QSAR 2018 and EPIsuite) and for the read across chemical from experimental lab reports (ABITEC reports and UERL lab and chemosphere 2014), it can be concluded that the substance 2-(3,4-dimethoxyphenyl)ethan-1-amine (120-20-7) is considered to be not toxic to aquatic environment (aquatic algae and cyanobacteria) and cannot be classified as toxic as per the criteria mentioned in CLP regulation.