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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 3.4
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):
Daphnia magna
Details on test organisms:
- Common name: Water flea
Test type:
static
Water media type:
freshwater
Total exposure duration:
48 h
Test temperature:
18-22°C
pH:
7.2 - 7.6
Reference substance (positive control):
not specified
Key result
Duration:
48 h
Dose descriptor:
EC50
Effect conc.:
206.07 mg/L
Nominal / measured:
estimated
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 ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and "m" )  and ("n" and ( not "o") )  )  and "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 >> Quinones and Trihydroxybenzenes OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane 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 Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after nitrenium ion formation 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 >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN2 OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups 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 Aliphatic Amines AND Phenol Amines AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Phenols, Poly by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Very fast by Bioaccumulation - metabolism half-lives ONLY

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 Cyanide / Nitriles   [-C#N] OR Ester   [-C(=O)-O-C] OR Four or more fused cyclic rings 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 Unsubstituted phenyl group (C6H5-) by Bioaccumulation - metabolism alerts

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as No Data by Ultimate biodeg

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as > 100 days by Ultimate biodeg

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as No Data by Ultimate biodeg

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as 1 to 10 days by Ultimate biodeg

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.599

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.67

Validity criteria fulfilled:
not specified
Conclusions:
Based on the intoxication of daphnia magna by the chemical 4-(2-aminoethyl)phenol (Tyramine) for 48 hrs, the EC50 was determine to be 206 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 six closest read across substances, toxicity on daphnia magna was predicted for 4-(2-aminoethyl)phenol (Tyramine) (51-67-2). Based on the intoxication of test organism the EC50 value was estimated to be 206 mg/l when 4-(2-aminoethyl)phenol (Tyramine) exposed to daphnia magna for 48 hrs. 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 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 3.4 with log kow as the primary descriptor and considering the six closest read across substances, toxicity on daphnia magna was predicted for 4-(2-aminoethyl)phenol (Tyramine) (51-67-2). Based on the intoxication of test organism the EC50 value was estimated to be 206 mg/l when 4-(2-aminoethyl)phenol (Tyramine) exposed to daphnia magna for 48 hrs. 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 cannot be classified as per the criteria mentioned in CLP regulation.     

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates
Effect concentration:
206 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 mobility and intoxication of invertebrates. 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 six closest read across substances, toxicity on daphnia magna was predicted for 4-(2-aminoethyl)phenol (Tyramine) (51-67-2). Based on the intoxication of test organism the EC50 value was estimated to be 206 mg/l when 4-(2-aminoethyl)phenol (Tyramine) exposed to daphnia magna for 48 hrs. 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 cannot be 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 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 611.3 mg/l for 4-(2-aminoethyl)phenol (Tyramine) in 48 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 study was used from peer reviewed journal (Comparative Biochemistry and Physiology 2009) for target chemical 4-(2-aminoethyl)phenol (Tyramine) (51-67-2). Aim of this study was to determine the effect of chemical 4-(2-aminoethyl)phenol (Tyramine) on the embryonic development, rotation movement and on behavior changes of Lymnaea stagnalis. Test conducted for 7 minutes only. Chemical was analytically monitored by using HPLC. Tyramine were removed from the egg capsules and placed into 1.5 mL microcentrifuge tubes, then homogenized with an ultrasonic homogenizer by 30% pulsed power for 15 s in 100 μL of ice-chilled 0.1 N perchloric acid containing 1 pmol/μL isoproterenol as an internal standard. Assay was repeated three times. Populations of adult L. stagnalis specimens were maintained in aquaria at 20–25 °C, supplied with aerated water. Egg masses were collected from the laboratory populations. The development of L. stagnalis embryos generally takes eight days and can be conveniently monitored through the transparent egg capsules. Test performed at nominal concentrations ranges from 0.13 mg/l to 137.18 mg/l and conducted in 4 replicates. Based on the changes on the distance moved and also change in direct movement of Lymnaea stagnalis (Great Pond Snail), by the chemical4-(2-aminoethyl)phenol (Tyramine), the LOEC was observed at 137.18 mg/l. As the experiment was not performed according to the standard guidelines and the exposure period was very low for the actual determination of effect on the test organisms, thus on that basis chemical was not included for classification.

 

ACD labs predicted median Lethal Concentration (LC50) of daphnia magna using v5.0.0.184. The value is supported by estimated Reliability Index (RI). Based on this, the LC 50 value for test item 4-(2-aminoethyl)phenol (Tyramine) was predicted to be 82 mg/l for Daphnia magna. On the basis of predicted value it can be concluded that the 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.

 

Similarly based on the average value of both models ( Leadscope Enterprise model and SciMatics SciQSAR model), the result were predicted in Battery model. Based on the Danish (Q)SAR Database, the 48 hours EC50 was estimated to be 18 mg/l on Daphnia Magna for substance 4-(2-aminoethyl)phenol (Tyramine) with immobilization 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 (99-96-7) from j-check. Determination of short term toxicity of 4-Hydroxybenzoic Acid on the mobility of daphnia magna for 48hrs. Study was performed according to the OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test. Static method was used for the measurement of toxicity. After the exposure of 48hrs, 50% immobilization was observed at 140 mg/l. Based on the immobilization of daphnia magna due to the exposure of chemical 4-Hydroxybenzoic acid, the EC50 was 140 mg/l. Thus based on the EC50 value it can be concluded that the chemical was nontoxic and can be consider to be not classified as toxic as per the CLP classification criteria.

 

Similarly for the same read across chemical from Water Research 1989 supports the nontoxic nature of chemical. Short term toxicity to Daphnia sp. study was carried out for 48 hrs. Acute Daphnia test was performed according to DIN 38412, Part II. The study was based on the effects of the test compound 4-hydroxy benzoic acid (CAS no. 99-96-7) on Daphnia magna in a static fresh water system at a temperature of 20°C and pH of 8.0±0.2, respectively. Test organism used for the study was 6-24 hr old and no feeding to the organism Daphnia magna was done during the test period. Exact concentration of test chemical used for the study was not known, but the concentration steps of the test solution were selected so as to give 3-4 EC values in a range between EC0 and EC100, of which at least one value was below and one above EC50.The test vessels were two 50 ml beakers and for volatile or strongly smelling substances, two 50 ml bottles with ground-glass stoppers each with 20 ml useful capacity. Two parallel preparations were made for each concentration step. Loading amounted to one test animal per 2 ml test medium as ten 6-24 h old daphnids were placed in each test and control vessel, i.e: 20 animals per concentration step. After a test period of 24 h and again after 48 h, the no. of animals in the control and test solutions that could still swim were counted. After 48 h it was also possible to measure the pH value in order to determine whether the hydrogen ion concentrations were in an acceptable range for the daphnids or whether the result had to be considered as having been influenced by a change in pH during the course of the test. Furthermore, the oxygen content was determined at the end of the test period in order to ensure that it had not fallen below a minimum oxygen concentration of 2 mg/l. The test was considered as valid when fewer than 10% of the animals in the control solutions were unable to swim, when the pH value was not below 7.0 and the O2 value was not below 4.0 m/l. Based on effect on mobility of the test organism Daphnia magna, the 24 hr EC0, EC50 and EC100 value was determined to be 181, 104 and 286 mg/l, respectively and 48 hr EC0, EC50 and EC100 value was determined to be 173, 19 and 204 mg/l, respectively. Thus, based on the 24 and 48 h EC50 value, it can be concluded that the substance 4-hydroxy benzoic acid can be considered as non-toxic to aquatic organisms and thus can be considered to be not classified as per the CLP classification criteria.

 

Based on the predicted data for the target chemical (from OECD QSAR 2018 and EPIsuite, peer reviewed journal (Comparative Biochemistry and Physiology 2009), Danish QSAR and ACD lab) and for the read across chemical from (j-check and Water Research 1989), 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 invertebrates) and cannot be classified as toxic as per the criteria mentioned in CLP regulation.