1-{4-[2-(benzyloxy)ethoxy]phenyl}-1,2-diphenylbutane-1,4-diol

Short-term toxicity to aquatic invertebrates

Administrative data

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

key study

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:

Several computational tools are nowadays available for applying in silico approaches. Among them, for QSAR predictions the following were selected and used:
- ACD/Percepta for the prediction of acute oral toxicity, skin and eye irritation, gene mutation (Ames test), micronucleus in vivo (rodent), carcinogenicity rat and mouse composite, acute aquatic toxicity (Daphnia), octanol-water partition coefficient (logKow)
- ECOSAR for the prediction of acute aquatic toxicity on (Daphnia) and chronic aquatic toxicity (Pimephales promelas)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-(4-(2-(benzyloxy)ethoxy)phenyl)-1,2-diphenylbutane-1,4-diol

EC Number:

939-875-7

Molecular formula:

C31H32O4

IUPAC Name:

1-(4-(2-(benzyloxy)ethoxy)phenyl)-1,2-diphenylbutane-1,4-diol

Test organisms

Test organisms (species):

Daphnia magna

Study design

Test type:

not specified

Water media type:

not specified

Results and discussion

Effect concentrations

Dose descriptor:

LC50

Effect conc.:

0.17 mg/L

Conc. based on:

test mat.

Remarks on result:

other: Reliability assessment BORDERLINE

Any other information on results incl. tables

In silico tool	LC50 (mg/l)	Applicability domain	Reliability assessment
ACD/Percepta	0.17	Reliability index = 0.42	BORDERLINE
ECOSAR	0.03	*LogKow = 6.24	NOT RELIABLE
CONSENSUS	0.17

ACD/Percepta ACD/Percepta acute aquatic toxicity on Daphnia prediction for 1-(4-(2-(benzyloxy)ethoxy)phenyl)-1,2-diphenylbutane-1,4-diol resulted to be equal to 0.17 mg/l. The prediction is borderline reliable, being the reliability index equal to 0.42. Together with the prediction, Percepta displays up to 5 most structurally similar structures from the training set along with experimental carcinogenicity on mouse results for the corresponding compounds. The structural similarity is evaluated by a fragmental approach. The information on the structurally similar compounds in the training set is used to further assess the reliability of the prediction, since it illustrates how the test compound, i.e. 1-(4-(2-(benzyloxy)ethoxy)phenyl)-1,2-diphenylbutane-1,4-diol, is represented in the training set. This analysis can also help to better understand the reliability index value. The five most similar structures from the training set were identified along with their acute aquatic toxicity data, as illustrated in Table 20. It has to be noted that they exhibit moderate similarity, with a similarity index lower than 0.7.

Phenyl Ether RN: 101-84-8

LC50 (mg/L) = 0.59 Similarity: 0.63

Diphenyl RN: 92-52-4

LC50 (mg/L) = 3.4 Similarity: 0.53

Diphenylamine RN: 112-39-4

LC50 (mg/L) = 2.0 Similarity: 0.52

1,1-Dichloro-2,2-bis(pchlorophe nyl)ethane RN: 72-54-8

LC50 (mg/L) = 0.044 Similarity: 0.51

Thiocarbanilide RN: 102-08-9

LC50 (mg/L) = 0.67 Similarity: 0.51

ECOSAR ECOSAR contains a library of class-based QSARs for predicting aquatic toxicity, overlaid with an expert decision tree for selecting the appropriate chemical class. The QSARs in ECOSAR are based on a linear mathematical relationship between the predicted log Kow values and the corresponding log of the measured toxicity values (mmol/L) for a suite of training set chemicals within each class of interest. For acute exposures on Daphnia and fish, the applicable log Kow range to derive reliable quantitative (numeric) values is up to log Kow 5.0. If the log Kow of the chemical exceeds 5.0 which generally indicate a poorly soluble chemical, “no effects at saturation” are expected in saturated solutions (Tolls et al., Integr Environ Assess Manag, 2009, 5(3),374-378). Molecular weight may also be considered to determine the absorption cut off limit for aquatic organisms. As the molecular weight of a chemical increases above 600, passive absorption through respiratory membranes decreases significantly. Therefore, for chemicals with molecular weights above 1000, it has been assumed that such absorption is negligible. Therefore, ECOSAR is not recommended for chemicals with molecular weights above 1000. ECOSAR applies different equations for neutral organics chemicals, often referred to as "baseline toxicity", and chemicals with excess toxicity. ECOSAR assigned 1-(4-(2-(benzyloxy)ethoxy)phenyl)-1,2-diphenylbutane-1,4-diol to the class of benzyl alcohols predicting a LC50 (48 hr) = 0.028 mg/L. However, ECOSAR provided a warning message because the chemical may not be soluble enough to measure the predicted effect.

Applicant's summary and conclusion

Conclusions:

The acute aquatic toxicity of 1-(4-(2-(benzyloxy)ethoxy)phenyl)-1,2-diphenylbutane-1,4-diol was predicted employing two predictors: ACD/Percepta and ECOSAR. The different predictors were employed in order to apply a consensus analysis to enhance the reliability of the prediction. In the consensus assessment only reliable predictions were taken into account. Thus, in this case, based on ACD/Percepta prediction, a LC50 value equal to 0.17 mg/L was predicted for 1-(4-(2-(benzyloxy)ethoxy)phenyl)-1,2-diphenylbutane-1,4-diol.