4-(2-aminoethyl)phenol

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to fish

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 OECD 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):

Danio rerio (previous name: Brachydanio rerio)

Test type:

static

Water media type:

freshwater

Total exposure duration:

96 h

Hardness:

569.0-865.3 mg CaCO3 / L

Test temperature:

14 ± 1 °C

pH:

7.9-8.3

Dissolved oxygen:

7.2 mg/L

Reference substance (positive control):

not specified

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

192.48 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: Nontoxic

Sublethal observations / clinical signs:

The prediction was based on dataset comprised from the following descriptors: LC50
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 "i" )  and "j" )  and "k" )  and ("l" and ( not "m") )  )  and "n" )  and "o" )  and ("p" and "q" )  )

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 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Thiols OR SN1 OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> N-Hydroxylamines by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

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: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Similarity boundary:Target: NCCc1ccc(O)cc1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Similarity boundary:Target: NCCc1ccc(O)cc1
Threshold=60%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.268

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.06

Validity criteria fulfilled:

not specified

Conclusions:

Based on the mortality of fish Danio rerio by the chemical 4-(2-aminoethyl) phenol for 96 hrs, the LC50 was determine to be 192.47 mg/l.

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, the short term toxicity on fish Danio rerio (previous name: Brachydanio rerio) was predicted for 4-(2-aminoethyl)phenol (Tyramine) (51-67-2). Based on the mortality of fishes, the LC50 value was estimated to be 192.47 mg/l for Danio rerio for 96hrs of duration. Based on this value it can be concluded that the substance 4-(2-aminoethyl)phenol (Tyramine) (51-67-2) is considered to be nontoxic 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, the short term toxicity on fish Danio rerio (previous name: Brachydanio rerio) was predicted for 4-(2-aminoethyl)phenol (Tyramine) (51-67-2). Based on the mortality of fishes, the LC50 value was estimated to be 192.47 mg/l for Danio rerio for 96hrs of duration. Based on this value it can be concluded that the substance 4-(2-aminoethyl)phenol (Tyramine) (51-67-2) is considered to be nontoxic to aquatic environment and not classified as per the criteria mentioned in CLP regulation.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

192.47 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 fishes. 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, the short term toxicity on fish Danio rerio (previous name: Brachydanio rerio) was predicted for 4-(2-aminoethyl)phenol (Tyramine) (51-67-2). Based on the mortality of fishes, the LC50 value was estimated to be 192.47 mg/l for Danio rerio for 96hrs of duration. Based on this value it can be concluded that the substance 4-(2-aminoethyl)phenol (Tyramine) (51-67-2) is considered to be nontoxic 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, 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 fish was predicted. On the basis of this programe, the LC 50 value for short term toxicity to fish was predicted to be1196.4 mg/l for 4-(2-aminoethyl)phenol (Tyramine) in 96 hrs. Based on this value it can be concluded that the substance 4-(2-aminoethyl)phenol (Tyramine) is considered to be not toxic to aquatic environment and cannot be classified as per the criteria mentioned in CLP regulation.

 

The third prediction was according to aquatic toxicity module i.e ACD/Labs I-Lab 2.0;Algorithm Version: v5.0.0.184 the lethal concentration (LC50) of the test substance 4-(2-aminoethyl)phenol (Tyramine) was predicted to be 86 mg/l on fish species Fathead minnow (Pimephales promelas). Based on the LC50 calculation the estimated Reliability Index (RI) of test chemical 4-(2-aminoethyl)phenol (Tyramine) predicted to be 0.55 (As per model substance have moderate and high reliability if RI > 0.5).Thus reported RII value indicate it has high reliability. And LC50 value indicate that the test substance 4-(2-aminoethyl)phenol (Tyramine) considered as toxic, harmful to aquatic organisms and thus can be classified in aquatic chronic 3 category as per the CLP 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.

 

Prediction done using average value of both models i.e Leadscope and SciMatics SciQSAR model and the result were predicted in Battery model. Based on the Danish (Q)SAR Database, the 96hours LC50 was estimated to be 76.05 mg/l on Pimephales promelas for substance 4-(2-aminoethyl)phenol (Tyramine) with mortality effects. Thus based on this value it can be concluded that the substance 4-(2-aminoethyl)phenol (Tyramine) (51-67-2) can be concluded as toxic and classified as aquatic chronic 3 category as per the criteria of CLP regulation. 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 fifth 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-Methoxy benzyl alcohol on the Zebra fish (Danio rerio). Test was conducted in compliance with the OECD guideline 203. The test substance was soluble in water. Therefore, the test solution was prepared by dissolving 1 g of the test substance in 4 liters of potable water (passed through reverse osmosis system) with continuous stirring for achieving test concentrations of 100 mg/L, respectively. Test conducted at limit test concentration 100 mg/l and Zebra fishes were exposed to this concentration for 96 hours. Test animal was collected from Orange City Aquarium, Sitabuldi, Nagpur, MS (India). 8 fishes exposed to the test concentration. Aeration in test vessels was provided 1 day before the start of experiment. After the exposure of chemical (mortality, visible symptoms, pH, Temperature, dissolved oxygen content) were recorded after 24 hours, 48 hours, 72 hours and 96 hours of the start of the experiment. Based on nominal concentrations, experimental median lethal Concentrations [LC-50 (96 h)] for 4-Methoxy benzyl alcohol CAS No.105-13-5 on Zebra fish (Danio rerio) was determined to be > 100 mg/L by observing the mortality. Thus based on LC50 it can be concluded that the chemical was nontoxic and can be consider to be not classified as per the CLP classification criteria.

 

Similarly in the sixth weight of evidence study for another read across chemical Paracetamol (103-90-2) from UERL lab report short term toxicity was carried out. Based on the nominal concentrations, experimental median lethal concentration [LC-50 (96 h)] for Paracetamol (CAS No. -103-90-2) in Danio rerio was found to be  > 100 mg/L on the basis of mortality effects in a 96 hour study. LC0 (96 hours) (highest concentration at which no mortality was observed) = 100 mg/L. LC50 (96 hours) Experimental = > 100 mg/L. LC100 (96 hours) (lowest concentration at which 100% mortality was observed) = No mortality Thus based on this LC50 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 fish (Danio rerio).

 

Based on the predicted data for the target chemical (from OECD QSAR 2018 and EPIsuite, Danish QSAR and ACD lab) 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 (Fishes) and cannot be classified as toxic as per the criteria mentioned in CLP regulation.