6-cyclohexyl-1-hydroxy-4-methylpyridin-2(1H)-one, compound with 2-aminoethanol (1:1)

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

no guideline available

Principles of method if other than guideline:

Data published on toxicity studies to aquatic invertebrates for 2-aminoethanol, neutral form of ethanolaminium cation.

GLP compliance:

not specified

Remarks:

Data published. No detailed information about GLP compliance.

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

32.6 mg/L

Conclusions:

In water at environmentally relevant pH, 2-aminoethanol will exist as ethanolaminium cation. For 2-aminoethanol, the neutral form of ethanolaminium cation, the lowest reliable short-term toxicity value to Daphnia Magna is EC50 (48h) = 32.6 mg/L (measured; pH = 7.3-9.1).

Reference 2

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

2017

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:

1. SOFTWARE
ECOSAR v1.11 model (US EPA, July 2012)

2. MODEL (incl. version number)
ECOSAR v1.11 model

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
O=C(N(O)C(=CC=1C)C(CCCC2)C2)C1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See METHODOLOGY DOCUMENT for the ECOlogical Structure-Activity Relationship Model (ECOSAR)(US EPA)

5. APPLICABILITY DOMAIN
In the development of the ECOSAR equations for neutral organics and classes with excess toxicity, the training sets generally include chemicals with log Kow values in the range of -3 to 8 and molecular weights less than 1000. However, the domain of the model is considered to be larger than the descriptor range of the training set of chemicals.It has been determined through empirical data that for acute toxicity endpoints, chemicals with a log Kow value >5.0 are generally expected to have no effects at saturation

6. ADEQUACY OF THE RESULT
The estimate value has been generated by a valid model. The model is applicable to Ciclopirox with the necessary level of reliability and is sufficiently relevant for the regulatory purpose.

Principles of method if other than guideline:

Software tool(s) used including version: ECOSAR v1.11 model (US EPA, July 2012).
Model(s) used: ECOSAR v1.11 model (US EPA, July 2012).
Model description: see field 'Justification for for type of information'
Justification of QSAR prediction: see field 'Justification for type of information'

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

16.34 mg/L

Conclusions:

Within the environmentally relevant pH range, a substantial fraction of 6-cyclohexyl-4-methyl-2-oxopyridin-2(1H)-olate anion will be in the neutral form (6-cyclohexyl-1-hydroxy-4-methylpyridin-2-one (Ciclopirox); CAS 29342-05-0; pKa (estimated) =6.84 (ChemAxon)).
EC50 (aquatic invertebrates-48h) for Ciclopirox is estimated to be 16.34 mg/l.

Description of key information

Since Ciclopirox olamine is an organic salt, it is expected to dissociate upon its release in the environment and to dissolve in water into 6-cyclohexyl-4-methyl-2-oxopyridin-2(1H)-olate anoin and ethanolaminium cation. Because of this dissociation behaviour, the assessment of Ciclopirox olamine toxicity to aquatic invertebrates was focused on dissociation products.

For 2-aminoethanol, the neutral form of ethanolaminium cation, the lowest reliable short-term toxicity value to Daphnia Magna is EC50 (48h) = 32.6 mg/L (measured; pH = 7.3-9.1). In water at environmentally relevant pH, 2-aminoethanol will exist as ethanolaminium cation.

Within the environmentally relevant pH range, a substantial fraction of 6-cyclohexyl-4-methyl-2-oxopyridin-2(1H)-olate anion will be in the neutral form (6-cyclohexyl-1-hydroxy-4-methylpyridin-2-one (Ciclopirox); CAS 29342-05-0; pKa (estimated) =6.84 (ChemAxon)).

For Ciclopirox no experimental data on short-term toxicity to aquatic invertebrates have been identified. Acute toxicity to aquatic invertebrates of Ciclopirox was primarily examined using ECOSAR v1.11 model (US EPA, July 2012).

ECOSAR v1.11 Results for Ciclopirox: 48-h LC50 for Daphnid: 16.34 mg/L.