3,4-dimethoxyphenethylamine

Endpoint summary

Description of key information

Short term toxicity to aq. invertebrates:

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 daphnia magna was predicted for 2-(3,4-dimethoxyphenyl)ethan-1-amine (120-20-7). Based on the intoxication of test organism the EC50 value was estimated to be 548.73 mg/l when 2-(3,4-dimethoxyphenyl)ethan-1-amine exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance 2-(3,4-dimethoxyphenyl)ethan-1-amine (120-20-7) is considered to be nontoxic to aquatic environment and cannot classified as per the criteria mentioned in CLP regulation.    

Toxicity to aq. algae and cyanobacteria:

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.    

Additional information

Summarized result for the determination of nature of chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine (120-20-7) on the growth and other biological and physical activity of aquatic invertebrates, algae and cyanobacteria when chemical comes in contact with test organisms, by considering the data for target as well as structurally and functionally similar read across chemicals which are as follows: 

 

Short term toxicity to aq. invertebrates:

 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 mobility of invertebrates. The studies are as mentioned below:   

 

The first weight of evidence for the target chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine (120-20-7) from SSS QSAR 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 daphnia magna was predicted for 2-(3,4-dimethoxyphenyl)ethan-1-amine (120-20-7). Based on the intoxication of test organism the EC50 value was estimated to be 548.73 mg/l when 2-(3,4-dimethoxyphenyl)ethan-1-amine exposed to daphnia magna for 48 hrs. Based on this value it can be concluded that the substance 2-(3,4-dimethoxyphenyl)ethan-1-amine (120-20-7) is considered to be nontoxic to aquatic environment and cannot 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 by using EPI suite, ECOSAR version 1.11, on the basis of similarity of structure to chemicals for which the aquatic toxicity has been previously measured by structure-activity relationships (SARs) program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted. On the basis of this programe, the LC 50 value for short term toxicity to aquatic invertebrates was predicted to be 630.6 mg/l for 2-(3,4-dimethoxyphenyl)ethan-1-amine in 48 hrs. Based on this value it can be concluded that the substance 2-(3,4-dimethoxyphenyl)ethan-1-amine is considered to be not toxic to aquatic environment and cannot be classified as per the criteria mentioned in CLP regulation.

 

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. Determination of the inhibition of the mobility of Daphnids was carried out with the substance 4-methoxyphenylacetic acid according to OECD Guideline 202. The stock solution 150.0 mg/L was prepared by dissolving white powder in reconstituted water. The solution was kept in ultrasonic bath for 20 min. The test solutions of required concentrations were prepared by mixing the stock solution of the test sample in reconstituted water. The test substance was tested at the concentrations 0, 30.0, 45.0, 67.5, 100.0 and 150.0 mg/L. The test was performed under static conditions in a fresh water system at a temperature of 20 °C± 1 °C. EC50 was calculated using nonlinear regression by the software Prism 4.0. The median effective concentration (EC50) for the test substance, 4-methoxyphenylacetic acid, in Daphnia magna was determined to be 100.8 mg/L for immobilisation effects with 95% CI of 94.7 to 107.4 mg/L. Thus, based on this EC50 value and after comparing with CLP criteria for aquatic classification of the substance it is concluded that the substance, 4-methoxyphenylacetic acid does not exhibit short term toxicity to aquatic invertebrate (Daphnia Magna).

 

The fourth study was conducted on the structurally and functionally similar read across chemical (121-34-6) from peer reviewed journal (chemosphere 2005). The acute immobilization toxicity of 4-Hydroxy-3-methoxybenzoic acid (Vanillic Acid) on the aromatic ring was determined for the freshwater crustacean Daphnia magna under neutralized condition. Test was performed under the static system at different concentrations ranges from 168.14 mg/l – 1681.4 mg/l (1-10 mmol/l). Solution was checked before and after (48 h) exposure experiments by the UV spectra (400–200 nm) using a UV–visible spectrophotometer, UV mini 1240. 50 ml glass beaker containing 40 ml of a test solution having 10 ml of headspace were used in the study. < 24 hrs Neonates obtain from National Institute for Environmental Studies (NIES), Tsukuba, Japan. Daphnia feeds once daily on3.0–3.5×108cells/l green alga Selenastrum capricornutum NIES-35. After the exposure of chemical effect were observed after 24 and 48 hrs. Based on the immobilization of daphnia magna by the exposure with chemical 4-Hydroxy-3-methoxy -benzoic acid (Vanillic Acid) for 48 hrs, the EC50 was determine to be 908 mg/l and at 24 hrs observed to be 1180 mg/l. Based on the EC50 value chemical 4-Hydroxy-3-methoxybenzoic acid (Vanillic Acid) was consider as nontoxic and can be consider to be not classified as per the CLP classification criteria.

 

Similarly in the fifth study on the read across chemical 2,4-Diamino-5-(3,4,5-trimethoxybenzyl)-pyrimidin (Trimethoprim) (738-70-5) (Ecotoxicology 2008) study was conducted to determine the toxicity of chemical 2,4-Diamino-5-(3,4,5-trimethoxybenzyl)-pyrimidin (Trimethoprim) on the mobility of daphnia magna. Test was performed according to the US EPA guideline. Effect concentration of chemical on Freshwater daphnia was tested by static system. Different measured concentration was directly prepared in dilution water. Organisms fed daily during the test. All water parameters measured daily. Immobilization was employed as an endpoint and considered to happen if no movement was detected for 15 s after gentle shaking of the test vehicle. Immobilization measured by probit analysis. After the exposure of chemical EC50 was measured at 24 and 48hrs, EC50 at 24hrs was 155.6 mg/l and at 48hrs 92.0 mg/l. Based on the immobilization of daphnia magna due to the exposure of chemical for 24hrs, the EC50 was 155.6 MG/L with 95% CI: 147.44 -163.700 mg/l. And on the basis of EC50 (155.6 mg/l), 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, chemosphere and Ecotoxicology 2008), 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 invertebrates) and cannot be classified as toxic as per the criteria mentioned in CLP regulation.    

 

 

Toxicity to aq. algae and cyanobacteria:

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.  

 

Thus based on the overall studies on both test organisms invertebrates and algae, finally chemical 120 -20 -7 was concluded as nontoxic and not classified as per the CLP classification criteria.