5-(1-methylpiperidin-4-yl)-5H-dibenzo[a,d][7]annulen-5-ol

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

Report date:

2014

Materials and methods

Principles of method if other than guideline:

The acute toxicity on Daphnia was estimated by using ACD/Percepta predictor for aquatic toxicity on Water flea (Daphnia magna) and ECOSAR.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-(1-methylpiperidin-4-yl)tricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,9,12,14-heptaen-2-ol

EC Number:

609-737-8

Cas Number:

3967-32-6

Molecular formula:

C21H23NO

IUPAC Name:

2-(1-methylpiperidin-4-yl)tricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,9,12,14-heptaen-2-ol

Test organisms

Test organisms (species):

Daphnia magna

Results and discussion

Effect concentrations

Dose descriptor:

LC50

Effect conc.:

3.02 mg/L

Remarks on result:

other: Reliable

Any other information on results incl. tables

ACD/Percepta LC50 (mg/L)	ECOSAR LC50 (mg/L)	Consensus prediction LC50 (mg/L)
7.2 (Borderline reliable)	0.24 (Reliable)	3.02 (Reliable)

ACD/Percepta

ACD/Percepta acute aquatic toxicity on Daphnia is provided with a reliability index (RI) parameter which estimates the reliability of the prediction. The reliability index takes into account the similarity of the tested compound with the training set compounds and the consistency of experimental values for similar compounds. Values greater than 0.75 indicate highly reliable predictions, values in the range 0.5-0.75 indicate moderately reliable predictions, values in the range 0.3-0.5 indicate borderline predictions, while for values lower than 0.3 predictions are considered as NOT reliable.

ACD/Percepta predicted for 5-(1-methylpiperidin-4-yl)-5H-dibenzo[a,d][7]annulen-5-ol a LC50 equal to 7.2 mg/L, and the prediction is of borderline reliability being the reliability index equal to 0.37. Together with the prediction, ACD/Percepta displays up to 5 most structurally similar structures from the training set along with their experimental test 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. 5-(1- methylpiperidin-4-yl)-5H-dibenzo[a,d][7]annulen-5-ol, is represented in the training set. The five mostly similar compounds from the training set, exhibit little similarity with respect to 5-(1- methylpiperidin-4-yl)-5H-dibenzo[a,d][7]annulen-5-ol (similarity index ranging from 0.27 to 0.55), meaning that the target compound is not well represented in the training set of the model. Thus, the little similarity of the training compounds led to the prediction being of borderline reliability.

ECOSAR ECOSAR predicts the aquatic toxicity of chemicals based on their similarity of structure to chemicals for which the aquatic toxicity has been previously measured. 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. The reliability of ECOSAR prediction is evaluated in terms of descriptor range (Kow range).

ECOSAR assigned 5-(1-methylpiperidin-4-yl)-5H-dibenzo[a,d][7]annulen-5-ol to the class of aliphatic amines and benzyl alcohols. According to a precautionary approach, the predicted LC50 value was selected as the lowest LC50 value (aliphatic amines LC50) among the LC50 values of the two classes. Thus, ECOSAR predicted a LC50 equal to 0.24 mg/L, and the prediction is considered reliable since the target does not exceed the upper logKow value of 5.0 (the consensus logKow value estimated 3.78).

Applicant's summary and conclusion

Conclusions:

Acute aquatic toxicity on Daphnia for the target 5-(1-methylpiperidin-4-yl)-5H-dibenzo[a,d][7]annulen-5-ol
was estimated by using two predictors: ACD/Percepta and ECOSAR. The two predictors were employed in
order to apply a consensus approach to enhance the reliability of the prediction. The consensus assessment
was computed as weighted mean between ACD/Percepta and ECOSAR predictions. Since ACD/Percepta
prediction resulted of borderline reliability, it was weighted less (weight = 0.4) than ECOSAR (weight = 0.6)
leading to the consensus acute aquatic toxicity on Daphnia prediction of LC50 equal to 3.02 mg/L.