2-aminoethanol hydrobromide

Toxicity to aquatic algae and cyanobacteria

Administrative data

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

(Q)SAR

Adequacy of study:

key study

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 adequate and reliable documentation / justification

Justification for type of information:

The target compound is a salt. The procedure commonly used to generate in silico predictions of salt substances consists in the removal of the counter ion (or the inorganic part, or the lowest MW part of the salt molecule) and, if necessary, the subsequent neutralization. This procedure is needed to calculate the descriptors used to make the predictions. This procedure was discussed and confirmed by several experts, both academic and regulators (European Agency for chemicals, ECHA). In the case of the target 2-aminoethanol hydrobromide, for modelling purposes, the chemical structure has been processed by removal of the inorganic part (HBr).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Principles of method if other than guideline:

QSAR model: “GREEN ALGAE 96-h EC50” model implemented in the ECOSAR estimation program.

ECOSAR (Ecological Structure Activity Relationships system) (U.S. Environmental Protection Agency, version 2.0) Class Program is a computerized predictive system that estimates aquatic toxicity. The program estimates a chemical's acute (short-term) toxicity and chronic (long-term or delayed) toxicity to aquatic organisms such as fish, aquatic invertebrates, and aquatic plants by using computerized Structure Activity Relationships (SARs).
Aquatic toxicity of untested chemicals is predicted based on their structural similarity to chemicals for which aquatic studies are available. The toxicity data used to build the SARs are collected from publicly available experimental studies and confidential submissions provided to the U.S. EPA New Chemicals Program. ECOSAR contains a library of class-based QSARs for predicting aquatic toxicity, overlaid with an expert decision tree for selecting the appropriate chemical class. ECOSAR derives toxicity values for three general types of chemicals: 1) Neutral Organics, i.e. nonionizable and nonreactive chemicals acting via simple nonpolar narcosis (baseline toxicity); 2) Organic Chemicals with Excess Toxicity, i.e. organic chemicals presenting a more specific mode of toxicity based on the presence of reactive functional groups (Hermens 1990). These chemicals can be more toxic than predicted by baseline toxicity equations to one or more aquatic organisms. Separate QSARs have been developed for several chemical classes identified as presenting excess toxicity to at least one or more species. 3) Surfactant (Surface-Active) Organic Chemicals, i.e. chemicals that can greatly reduce the surface tension of water when used in very low concentrations. Surfactants do not typically dissolve in water; instead, they form micelles. Within ECOSAR, the surfactants are grouped into four general divisions by total charge: anionic (net negative charge), cationic (net positive charge), nonionic (neutral), and amphoteric surfactants. The QSARs for surfactants can be linear or parabolic and the toxicity is often related to the size of the hydrophobic component or the number of repeating hydrophilic components. The QSARs in ECOSAR for both neutral organics and classes with excess toxicity are based on a linear mathematical relationship between the predicted log Kow values (EPI Suite KOWWIN prediction) and the corresponding log of the measured toxicity values (mmol/L) for a suite of training set chemicals within each class of interest. The studies collected for the training set chemicals in ECOSAR undergo an extensive data validation step to ensure appropriateness for inclusion in the model. ECOSAR predictions are not supported by a specific parameter for the assessment of their reliability and models applicability domain. However, it is generally assumed that toxicity estimates are less accurate for compounds outside the descriptor (i.e., LogKow) and molecular weight (MW) ranges of the training set compounds. Additionally, a LogKow cut-off is defined for the applicability of the ECOSAR models (generally, the log Kow cut-off for QSARs predicting acute effects is equal to 5.0, the cut-off for QSARs predicting chronic effects is equal to 8.0). Above these cut-offs, data generally indicate that the hydrophobicity of the molecules leads to “no effects at saturation”.

GLP compliance:

no

Test material

Reference

Name:

Unnamed

Type:

Constituent

Results and discussion

Effect concentrations

Key result

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

ca. 251.43 mg/L

Details on results:

The prediction is considered moderately reliable (i.e. target compound is included in the applicability domain of the model and prediction is assessed as moderately accurate (rather limited uncertainty)).
The target compound is included in the applicability domain of the model since it is characterized by MW (61.08 g/mol) and LogKow (-1.31) values below the defined thresholds, respectively 1000 and 6.4. Additionally it was noted that both MW and LogKow values of the target are included in the ranges of training set chemicals.
- descriptor domain: LogKow of the target compound has a value inside the LogKow range of the compounds of the training set.
- structural fragment domain: alkyl amine fragment is represented in the model training set.

Any other information on results incl. tables

Prediction: Acute EC50 (algae) equal to 251.43 mg/L.

ECOSAR assigned the target chemical 2-aminoethanol to the class of Excess Toxicity “Aliphatic Amines”. ECOSAR currently identifies several different types of structures as Aliphatic Amines. For the target compound, the sub-class “Normal Aliphatic Amines” was identified, where carbon attachments to the nitrogen are exclusively aliphatic carbons (alkyl, olefinic or acetylenic carbon). Prediction based on the Neutral Organics equation is provided to allow the assessment of predicted excess toxicity compared to baseline (non-polar) narcosis. Since at least one class of excess toxicity is identified for the target, the prediction based on the Neutral Organics equation is not applicable since it could under-estimate potential toxicity of the target. The ECOSAR prediction was executed using as input value the experimental LogKow available for the target 2-aminoethanol (-1.31, PhysProp DB experimental value).

Applicability Domain (AD): ECOSAR models for Aliphatic Amines can be applied to estimate toxicity for aliphatic amines. Predictions provided by ECOSAR are not supported by a specific parameter for reliability assessment, however a LogKow cut-off (class-dependent) and a MW cut-off equal to 1000 are used to define the limits of the applicability domain of the model. Additionally, more accurate predictions are expected for chemicals characterised by a MW falling within the MW range of the training set compounds. The target compound is included in the applicability domain of the model since it is characterized by MW (61.08 g/mol) and LogKow (-1.31) values below the defined thresholds, respectively 1000 and 6.4. Additionally it was noted that both MW and LogKow values of the target are included in the ranges of training set chemicals.

The target compound is included in the applicability domain of the model since it is characterized by MW (61.08 g/mol) and LogKow (-1.31) values below the defined thresholds, respectively 1000 and 6.4. Additionally it was noted that both MW and LogKow values of the target are included in the ranges of training set chemicals.

- descriptor domain: LogKow of the target compound has a value inside the LogKow range of the compounds of the training set.

- structural fragment domain: alkyl amine fragment is represented in the model training set.

Structural analogues: No structural analogues from the training set are automatically provided by ECOSAR. However, the training set of the model being available, three structurally similar compounds have been identified (illustrated in Table below). These compounds exhibit moderate similarity toward the target 2-aminoethanol (similarity index in the range 0.65-0.81, index calculated by ACD/Spectrus DB Enterprise) and experimental 96hr-EC50 values ranging from 13 mg/L (Propenamine) to 480 mg/L (2-Amino-2-methyl-1-propanol).

Name of analogue	Experimental LC50 (mg/L)	Similarity	Reference
Ethylenediamine (CAS 107-15-3)	61	0.81	Van Leeuwen et al., 1985
Propenamine (CAS 107-11-9)	13	0.68	Sloof, 1983
2-Amino-2-methyl-1- propanol (CAS 124-68-5)	480	0.65	Freitag & Korte, 1989

Prediction uncertainty & reliability: ECOSAR predictions are not supported by a specific parameter for the assessment of their uncertainty/reliability. Prediction reliability was then assessed based on the following criteria: i) scientific validity of the model; ii) applicability domain; iii) similarity and experimental data consistency of training set structural analogues. For the target 2-aminoethanol, the ECOSAR prediction, based on Aliphatic Amine equation, was assessed as moderately reliable based on the following considerations:

- the ECOSAR model for green algae 96-hr toxicity is considered as sufficiently robust (n = 35, R2 = 0.78).

- the target compound is included in the applicability domain of the model.

- training set analogues similarity: moderate.

- experimental data of training set analogues: 96-hr EC50 values in the range 13 – 480 mg/L (almost consistent with the predicted value of the target).

Finally, it is highlighted that an experimental 96-hr EC50 data in algae is available for the target 2-aminoethanol from the ECOSAR Database (96h-EC50: 80 mg/L - no species specified). Despite the available experimental data is lower than the predicted 96h-EC50 value (251.43 mg/L), both values are greater than the acute aquatic toxicity classification threshold of 1 mg/L.

Adequacy: The acute toxicity on algae QSAR prediction was assessed as adequate for regulatory purposes (Klimisch 2 - result derived from a valid QSAR model and falling into its applicability domain, with adequate and reliable documentation/justification).

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

This study was designed to generate estimated in silico (non-testing) data for 2-aminoethanol hydrobromide (CAS 23382-12-9) to be used for its hazard assessment. For modelling purposes, the chemical structure of 2-aminoethanol hydrobromide has been processed in silico by removal of the inorganic part (HBr). Thus, in the current report the in silico assessment was performed for 2-aminoethanol.

Based on QSAR “GREEN ALGAE 96-h EC50” model of ECOSAR program, the 96-h LC50 (algae) for 2-aminoethanol hydrobromide is predicted to be equal to 251.43 mg/L.
The prediction is considered moderately reliable (i.e. target compound is included in the applicability domain of the model and prediction is assessed as moderately accurate (rather limited uncertainty)).
It can be considered that the result on green algae, 96h-EC50 covers the 72h-EC50. Therefore, the substance is expected to be not toxic to the green algae.