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

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

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 Daphnia EC50 for the ester Veramoss is predicted to be 9.3 mg/L based on the ECOSAR SAR for esters using an estimated log Kow of 3.2, molecular weight of 196.2 and the equation: Log 48h-LC50 (mmol/L) = -0.6305 (log Kow) + 0.7049, the LC50 of ECOSAR being equivalent to the EC50 because predictions are derived from OECD guideline measured data.
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 (=< 5); 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 18.6 mg/L and a measured of 45 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 acute Daphnia 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

Version / remarks:

In the QMR attached the model specifications are presented. In this QMR is referenced to the Methodology document for the ecological Structure-Activity Relationship model (ECOSAR) Class Programm MS Windows v1.1'. United States Environmental Protection Agency, Office of Pollution Prevention and Toxics, Washington DC (2011).

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):

Daphnia sp.

Water media type:

freshwater

Total exposure duration:

48 h

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

9.3 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: QSAR predicted value

Remarks:

ECOSAR class: Esters

ECOSAR v1.11 predicted that the 48h-EC50 of Veramoss to Daphnia is 9.3 mg/L.

Validity criteria fulfilled:

yes

Remarks:

The ECOSAR-Ester equation is valid when using the OECD criteria. In addition, N=40 and R2 is 0.80

Conclusions:

ECOSAR v1.11 predicted that the 48h-EC50 of Veramoss to Daphnia is 9.3 mg/L.

Executive summary:

See section 'Justification of information' or the Endpoint summary.

Description of key information

The acute Daphnia EC50 for the ester Veramoss is predicted to be 9.3mg/L based on the ECOSAR SAR for esters using an estimated log Kow of 3.2,molecular weight of 196.2 and the equation: Log 48h-LC50 (mmol/L) = -0.6305 (log Kow) + 0.7049

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 (=< 5); 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 but no structural analogue is found. A substance with a somewhat similar predicted log Kow (2.8) is octyl lactate with a predicted EC50 of 18.6 mg/L and a measured of 45 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 acute Daphnia toxicity on esters. The adequate and reliable documentation further supports this prediction.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

9.3 mg/L

Additional information

Experimental study according to OECD TG 202

An experimentally derived Daphnia magna 48h-EC50 of 18 mg/L is also available (study with limitations, Kl. 2), which indicates that the calculated value is conservative.