4-(2-aminoethyl)phenol

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 3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material : 4-(2-aminoethyl) phenol
- Common name : Tyramine
- Molecular formula : C8H11NO
- Molecular weight : 137.1809 g/mol
- Smiles notation : NCCc1ccc(O)cc1
- InChl : 1S/C8H11NO/c9-6-5-7-1-3-8(10)4-2-7/h1-4,10H,5-6,9H2
- Substance type: Organic
- Physical state: Solid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Desmodesmus subspicatus (previous name: Scenedesmus subspicatus)

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Test temperature:

22.5 - 23.0°C

pH:

7.5 - 8.2

Reference substance (positive control):

not specified

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

117.422 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 ( not "g") )  )  and ("h" and ( not "i") )  )  and "j" )  and "k" )  and "l" )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and "z" )  )

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 AND Phenols (Acute toxicity) 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 >> Alkyl phenols by DNA binding by OECD

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols by Protein binding by OASIS v1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >> Nucleophilic addition reaction with cycloisomerization OR AN2 >> Nucleophilic addition reaction with cycloisomerization >> Hydrazine Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN2 OR SN2 >> Direct nucleophilic attack on diazonium cation OR SN2 >> Direct nucleophilic attack on diazonium cation >> Hydrazine Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR Acylation >> Ring Opening Acylation OR Acylation >> Ring Opening Acylation >> alpha-Lactams by Protein binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Class 2 (less inert compounds) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Class 2 (less inert compounds) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Phenols and Anilines by Acute aquatic toxicity MOA by OASIS ONLY

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 alcohol  [-OH] AND Aromatic-CH2 AND Aromatic-H AND Benzene AND -CH2-  [linear] 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 alcohol  [-OH] AND Aromatic-CH2 AND Aromatic-H AND Benzene AND -CH2-  [linear] 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 alcohol  [-OH] AND Aromatic-CH2 AND Aromatic-H AND Benzene AND -CH2-  [linear] by Bioaccumulation - metabolism alerts

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Aromatic bromide   [-Br] OR Aromatic chloride   [-CL] OR Aromatic ether  [-O-aromatic carbon] 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 alcohol  [-OH] AND Aromatic-CH2 AND Aromatic-H AND Benzene AND -CH2-  [linear] by Bioaccumulation - metabolism alerts

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Aromatic-CH3 by Bioaccumulation - metabolism alerts

Domain logical expression index: "u"

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

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Linear C4 terminal chain  [CCC-CH3] by Bioaccumulation - metabolism alerts

Domain logical expression index: "w"

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

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Tertiary amine by Bioaccumulation - metabolism alerts

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0587

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.33

Validity criteria fulfilled:

not specified

Conclusions:

Based on the growth rate inhibition the EC50 value was estimated to be 117.4 mg/l when 4-(2-aminoethyl)phenol (Tyramine) exposed to Desmodesmus subspicatus for 72 hrs.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on Desmodesmus subspicatus (previous name: Scenedesmus subspicatus) predicted 4-(2-aminoethyl)phenol (Tyramine) (51-67-2). Based on the growth rate inhibition the EC50 value was estimated to be 117.4 mg/l when 4-(2-aminoethyl)phenol (Tyramine) exposed to Desmodesmus subspicatus for 72 hrs. Based on this value it can be concluded that the substance 4-(2-aminoethyl)phenol (Tyramine) (51-67-2) considered to be not toxic to aquatic environment and not classified as per the criteria mentioned in CLP regulation.      

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on Desmodesmus subspicatus (previous name: Scenedesmus subspicatus) predicted 4-(2-aminoethyl)phenol (Tyramine) (51-67-2). Based on the growth rate inhibition the EC50 value was estimated to be 117.4 mg/l when 4-(2-aminoethyl)phenol (Tyramine) exposed to Desmodesmus subspicatus for 72 hrs. Based on this value it can be concluded that the substance 4-(2-aminoethyl)phenol (Tyramine) (51-67-2) considered to be not toxic to aquatic environment and not classified as per the criteria mentioned in CLP regulation.      

Key value for chemical safety assessment

EC50 for freshwater algae:

117.4 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 4-(2-aminoethyl)phenol (Tyramine) (51-67-2) on the growth of algae. The studies are as mentioned below:   

 

The first weight of evidence for the target chemical 4-(2-aminoethyl)phenol (Tyramine) (51-67-2) from SSS QSAR 2017 prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, toxicity on Desmodesmus subspicatus (previous name: Scenedesmus subspicatus) predicted 4-(2-aminoethyl)phenol (Tyramine) (51-67-2). Based on the growth rate inhibition the EC50 value was estimated to be 117.4 mg/l when 4-(2-aminoethyl)phenol (Tyramine) exposed to Desmodesmus subspicatus for 72 hrs. Based on this value it can be concluded that the substance 4-(2-aminoethyl)phenol (Tyramine) (51-67-2) considered to be not toxic to aquatic environment and not classified as per the criteria mentioned in CLP regulation.    

Similarly in the second predicted data for (4-(2-aminoethyl)phenol (Tyramine) (51-67-2) ) done by EPI suite, ECOSAR version 1.1 the short term toxicity on green algae was predicted for test substance 4-(2-aminoethyl)phenol (Tyramine) (CAS:51-67-2). On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 294.4 mg/l for green algae for 96 hrs duration. Based on this value, it can be concluded that the test chemical 4-(2-aminoethyl)phenol (Tyramine) 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.

 

 

Based on the prediction done using the three different models i.e, Battery, Leadscope and SciQSAR used within Danish QSAR database, the short term toxicity on green algae was predicted for test substance 4-(2-aminoethyl)phenol; Tyramine (CAS: 51 -67 -2). The average EC50 value was given by the third model i.e, Battery model. On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance 4-(2-aminoethyl)phenol; Tyramine is estimated to be 68.2 mg/l for Pseudokirchneriella subcapitata during 72 hr exposure duration. Thus, on the basis of EC50 value, it can be concluded that the test chemical 4-(2-aminoethyl)phenol; Tyramine can be considered as toxic to green algae at environmentally relevant concentrations and can be considered to be classified in aquatic chronic category 3 as per the CLP classification criteria. But as the chemical was readily biodegradable in water thus on that basis it is concluded that the chemical was nontoxic and not classified as per the CLP classification criteria.

 

Above predicted data was supported by the fourth experimental weight of evidence study for the read across chemical (105-13-5) from UERL lab 2014. 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 in the fifth weight of evidence study for another read across chemical Paracetamol (103-90-2) from UERL lab report short term toxicity was carried out. The effect of test item paracetamol, CAS No. 103-90-2 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 6.25mg/l, 12.5mg/l, 25mg/l, 50mg/l, 100mg/l and 200mg/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 112.666mg/l. Based on this EC50 value and after comparing with CLP criteria for aquatic classification of the substance it is concluded that the substance Paracetamol does not exhibit toxicity to aquatic algae (Chlorella vulgaris).

 

Based on the predicted data for the target chemical (from OECD QSAR 2018 and EPIsuite, Danish QSAR) and for the read across chemical from experimental lab reports (UERL), it can be concluded that the substance 4-(2-aminoethyl)phenol (Tyramine) (51-67-2) is considered to be not toxic to aquatic environment (aquatic algae) and cannot be classified as toxic as per the criteria mentioned in CLP regulation.