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Short-term toxicity to aquatic invertebrates

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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:
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):
Daphnia magna
Details on test organisms:
- Common name: Water flea
Test type:
static
Water media type:
freshwater
Total exposure duration:
48 h
Hardness:
40.5 mg/L (as CaC03)
Test temperature:
20±1°C
pH:
7.6
Reference substance (positive control):
not specified
Key result
Duration:
48 h
Dose descriptor:
EC50
Effect conc.:
548.73 mg/L
Nominal / measured:
nominal
Conc. based on:
not specified
Basis for effect:
other: Intoxication
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 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and "o" )  )

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 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: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Methylenedioxyphenyl OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR No alert found OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes >> N-methylol derivates OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic nitro OR SN2 OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Halogenated polarised alkenes by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup by Estrogen Receptor Binding

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Halogens by Groups of elements

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Phenols (Mucous membrane irritation) Rank C by Repeated dose (HESS)

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.73

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.22

Validity criteria fulfilled:
not specified
Conclusions:
Based on the intoxication of daphnia magna by the chemical, the EC50 was estimated to be 548.73 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 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.    

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 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.    

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates
Effect concentration:
548.73 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 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.    

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