Methyl 2,4-dihydroxy-3,6-dimethylbenzoate

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2016

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 chronic algae toxicity for the ester Veramoss is predicted to be 1.2 mg/L based on the ECOSAR SAR for esters using an estimated log Kow of 3.2, molecular weight of 196.2 g/mol and the equation: Log 96h ChV (mmol/L) = -0.5583 (log Kow) - 0.4017. The ChV (chronic value) is considered equivalent to EC10 because the predicted chronic values in ECOSAR are based on the OECD TG 201 guideline.
Veramoss is in the applicability domain of the ECOSAR prediction because: a) Veramoss is an ester presenting the toxicity solely by its bioavailability (i.e. without fragments that activate this ester); b) its log Kow is 3.2 (=< 8.0); c) its MW is 196.2 g/mol (< 1000); and; d) the toxicity predicted is below its measured water solubility of 18 mg/L.
In the ECOSAR training set esters are available with log Kows around the Veramoss value.A substance with a somewhat similar predicted log Kow (3.7) is ethyl hexyl acetate with a predicted EC10 of 0.56 mg/L and measured value of 15 mg/L. The fit in the applicability domain and the availability of an analogue in the training set results in limited uncertainty of the Veramoss prediction. This shows that the prediction is reliable and a Klimisch 2 can be assigned. In accordance with REACH Annex XI, the validity of the (Q)SAR is documented in a QMR for chronic algae toxicity on esters (see attached report). The adequate and reliable documentation, presented below, further supports this prediction.

Qualifier:

according to guideline

Guideline:

other: IR/CSR Guidance R.6 QSARs and grouping of chemicals, May 2008

Deviations:

not applicable

GLP compliance:

no

Specific details on test material used for the study:

SMILES: O=C(OC)c(c(cc(O)c1C)C)c1O

Test organisms (species):

other: green algae

Water media type:

freshwater

Total exposure duration:

96 h

Key result

Duration:

96 h

Dose descriptor:

EC10

Effect conc.:

1.2 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: QSAR estimation

Remarks:

ECOSAR Class: Esters which predicts a chronic value (ChV) equivalent to EC10.

Details on results:

Veramoss prediction for chronic algae toxicity results in a value of 1.2 mg/L.

Validity criteria fulfilled:

yes

Remarks:

The ECOSAR-Ester equation is valid when using the OECD criteria. In addition, N=13 and R2 is 0.74

Conclusions:

Veramoss prediction for chronic algae toxicity results in 1.2 mg/L.

Executive summary:

See 'Justification of information' section or Endpoint summary on Toxicity to aquatic algae

Reference 2

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

July 2016

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 acute algae ErC50 for the esters Veramoss is predicted to be 3.3 mg/L based on the ECOSAR SAR for esters using an estimated log Kow of 3.2, molecular weight of 196.2 g/mol and the equation: Log 96-h EC50 (mmol/L) = -0.6993 (log Kow) + 0.4715. The 96h is equivalent to the current OECD 201 guideline because the QSAR is based on measured data from the OECD TG 201.
Veramoss is in the applicability domain of the ECOSAR prediction because: a) Veramoss is an ester presenting the toxicity solely by its bioavailability (i.e. without fragments that activate this ester); b) its log Kow is 3.2 (=< 6.4); c) its MW is 196.2 g/mol (< 1000); and; d) the toxicity predicted is below its measured water solubility of 18 mg/L.
In the ECOSAR training set esters are available with log Kows around the Veramoss value. A substance with a somewhat similar predicted log Kow (2.8) is Octyl lactate with a predicted EC50 of 7.0 and a measured value of 7.6 mg/L.
In accordance with REACH Annex XI, the validity of the (Q)SAR is documented in a QMR for acute algae toxicity on esters (see attached report). The adequate and reliable documentation, presented below, further supports this prediction.

Qualifier:

according to guideline

Guideline:

other: IR/CSR Guidance R.6 QSARs and grouping of chemicals, May 2008

Deviations:

not applicable

Specific details on test material used for the study:

SMILES: O=C(OC)c(c(cc(O)c1C)C)c1O

Test organisms (species):

other: green algae

Water media type:

freshwater

Total exposure duration:

96 h

Key result

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

3.3 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: QSAR predicted value

Remarks:

ECOSAR class: Esters

Validity criteria fulfilled:

yes

Remarks:

The ECOSAR-Ester equation is valid when using the OECD criteria. In addition, N=20 and R2 is 0.86

Conclusions:

ECOSAR v1.11 predicted that the 96h-EC50 of Veramoss to green algae is 3.3 mg/L.

Executive summary:

See Justification of information or Endpoint summary of Toxicity to algae.

Description of key information

Acute algae toxicity using ECOSAR

The acute algae ErC50 for the esters Veramoss is predicted to be 3.3mg/L based on the ECOSAR SAR for esters using an estimated log Kow of 3.2,molecular weight of 196.2 g/mol and the equation: Log 96-h EC50 (mmol/L) = -0.6993 (log Kow) + 0.4715. The 96h is equivalent to the current OECD 201 guideline because the QSAR is based on measured data from the OECD TG 201.

Veramoss is in the applicability domain of the ECOSAR prediction because: a) Veramoss is an ester presenting the toxicity solely by its bioavailability (i.e. without fragments that activate this ester); b) its log Kow is 3.2 (=< 6.4); c) its MW is 196.2 g/mol (< 1000); and; d) the toxicity predicted is below its measured water solubility of 18 mg/L.

In the ECOSAR training set esters are available with log Kows around the Veramoss value. A substance with a somewhat similar predicted log Kow (2.8) is Octyl lactate with a predicted EC50 of 7.0 and a measured value of 7.6 mg/L.

In accordance with REACH Annex XI, the validity of the (Q)SAR is documented in a QMR for acute algae toxicity on esters (see attached report). The adequate and reliable documentation, presented below, further supports this prediction.

Chronic algae toxicity by ECOSAR

The chronic algae toxicity for the ester Veramoss is predicted to be 1.2mg/L based on the ECOSAR SAR for esters using an estimated log Kow of 3.2,molecular weight of 196.2 g/mol and the equation: Log 96h ChV (mmol/L) = -0.5583 (log Kow) - 0.4017. The ChV (chronic value) is considered equivalent to EC10 because the predicted chronic values in ECOSAR are based on the OECD TG 201 guideline.

Veramoss is in the applicability domain of the ECOSAR prediction because: a) Veramoss is an ester presenting the toxicity solely by its bioavailability (i.e. without fragments that activate this ester); b) its log Kow is 3.2 (=< 8.0); c) its MW is 196.2 g/mol (< 1000); and; d) the toxicity predicted is below its measured water solubility of 18 mg/L.

In the ECOSAR training set esters are available with log Kows around the Veramoss value.A substance with a somewhat similar predicted log Kow (3.7) is ethyl hexyl acetate with a predicted EC10 of 0.56 mg/L and measured value of 15 mg/L. The fit in the applicability domain and the availability of an analogue in the training set results in limited uncertainty of the Veramoss prediction. This shows that the prediction is reliable and a Klimisch 2 can be assigned. In accordance with REACH Annex XI, the validity of the (Q)SAR is documented in a QMR for chronic algae toxicity on esters (see attached report). The adequate and reliable documentation, presented below, further supports this prediction.

Key value for chemical safety assessment

EC50 for freshwater algae:

3.3 mg/L

EC10 or NOEC for freshwater algae:

1.2 mg/L