Bis[2-[2-(2-butoxyethoxy)ethoxy]ethyl] adipate

Short-term toxicity to fish

Administrative data

Endpoint:

short-term toxicity to fish

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

2013

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Principles of method if other than guideline:

QSAR approach: Different tools were used, when possible, in order to apply a consensus approach and thus enhance the reliability of the predictions. In fact, a single in silico prediction model may provide acceptable results. However, by definition all models are simulation of reality, and therefore they will never be completely accurate; sometimes a single model will not work. When multiple models and multiple approaches are combined in a single consensus score, more accurate predictions can be achieved.
If two prediction methods that use data and different approaches are consistent, the reliability of prediction is better. The errors of a model/approach should be different from another, and therefore compensate.

Several computational tools are nowadays available for applying in silico approaches. Among them, for QSAR predictions the following was selected and used for the endpoint:
ACD/Percepta (Advanced Chemistry Development, Inc., Pharma Algorithms, Inc.) (release 2012) is a suite of comprehensive tools for the prediction of basic toxicity endpoints, including hERG Inhibition, CYP3A4 Inhibition, Genotoxicity, Acute Toxicity, Aquatic Toxicity, Eye/Skin Irritation, Endocrine System Disruption, and Health Effects. Predictions are made from chemical structure and based upon large validated databases and QSAR models, in combination with expert knowledge of organic chemistry and toxicology. It also allows to evaluate the robustness of the prediction by examining compounds similar to the target from the training set, together with literature data and reference. The models also provide an estimation of the reliability of the prediction, by a reliability index (RI). This index provides values in a range from 0 to 1 and gives an evaluation of whether a submitted compound falls within the Model Applicability Domain. Estimation of the RI takes into account the following two aspects: similarity of the tested compound to the training set and the consistency of experimental values for similar compounds. If the RI is less than 0.3 the prediction has to be considered not reliable while if RI is more than 0.5 the prediction results are considered reliable.
ECOSAR (Ecological Structure Activity Relationships system) (US Environmental Protection Agency’s Office of Pollution Prevention and Toxics, version 1.11) 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. The SARs in ECOSAR express correlations between a compound's physicochemical properties and its toxicity within specific chemical classes.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Bis[2-[2-(2-butoxyethoxy)ethoxy]ethyl] adipate

EC Number:

265-807-4

EC Name:

Bis[2-[2-(2-butoxyethoxy)ethoxy]ethyl] adipate

Cas Number:

65520-46-9

Molecular formula:

C26H50O10

IUPAC Name:

1,6-bis({2-[2-(2-butoxyethoxy)ethoxy]ethyl}) hexanedioate

Test material form:

other: liquid

Results and discussion

Effect concentrations

Dose descriptor:

LC50

Effect conc.:

12 mg/L

Nominal / measured:

nominal

Any other information on results incl. tables

Sublethal observations / clinical signs:

The ACD/Percepta predictions of aquatic toxicity on Pimephales promelas resulted to be reliable.

ECOSAR predictions of acute aquatic toxicity on Pimephales promelas for bis(2-(2-(2-butoxyethoxy)ethoxy)ethyl) adipate resulted to be NOT reliable, since a warning on the predictions is provided due to the fact that it may not be soluble enough to measure the predicted effect.

The consensus predictions were computed taking into account only reliable predictions and according to a precautionary approach.

Acute aquatic toxicity on Pimephales promelas predictions.

*chemical may not be soluble enough to measure the predicted effect.

Chemical	ACD/Percepta LC50 (mg/L)	Reliability index	ECOSAR LC50 (mg/l) (48 hr)	ECOSAR Assessment	CONSENSUS PREDICTIONLC50 (mg/L)
bis(2-(2-(2-butoxyethoxy)ethoxy)ethyl) adipate	12	0.62	27.734*	Chemical may not be soluble enough to measure the predicted effect	12

Applicant's summary and conclusion

Conclusions:

ECOSAR predictions of acute aquatic toxicity on Pimephales promelas for bis(2-(2-(2-butoxyethoxy)ethoxy)ethyl) adipate resulted to be NOT reliable, since a warning on the predictions is provided due to the fact that it may not be soluble enough to measure the predicted effect.