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Toxicity to reproduction

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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: in silico prediction
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.
Leadscope Model Applier (Leadscope, Inc.) (version 1.4.6-2) is a chemoinformatic platform that provides QSAR for the prediction of potential toxicity and adverse human clinical effects of pharmaceuticals, cosmetics, food ingredients and other chemicals. The Models are constructed by FDA scientists based on both proprietary and non-proprietary data. Predictions are provided together with several parameters which can be used to assess the prediction in terms of applicability domain. The robustness of the prediction can be further evaluated by examining compounds similar to the target from the training set.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
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:
bis{2-[2-(2-butoxyethoxy)ethoxy]ethyl} adipate
Test material form:
other: liquid

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Remarks on result:
other: QSAR prediciton

Target system / organ toxicity (P0)

Critical effects observed:
not specified

Results: P1 (second parental generation)

Effect levels (P1)

Remarks on result:
other: QSAR prediciton

Target system / organ toxicity (P1)

Critical effects observed:
not specified

Results: F1 generation

Effect levels (F1)

Remarks on result:
other: QSAR prediciton

Target system / organ toxicity (F1)

Critical effects observed:
not specified

Results: F2 generation

Effect levels (F2)

Remarks on result:
other: QSAR prediciton

Target system / organ toxicity (F2)

Critical effects observed:
not specified

Overall reproductive toxicity

Reproductive effects observed:
no

Any other information on results incl. tables

Leadscope reproductive toxicity on mouse male predictions:

Chemical

Leadscope

Prediction

call

Leadscope

Positive

Prediction probability

Prediction reliability parameters

Model Fragment

Count

30% Sim. Training Neighbors Count

Reliability

assessment

bis(2-(2-(2-butoxyethoxy)ethoxy)ethyl) adipate

NEGATIVE

0.44

7

1

RELIABLE

Leadscope reproductive toxicity on mouse female predictions:

Chemical

Leadscope

Prediction

call

Leadscope

Positive

Prediction probability

Prediction reliability parameters

Model Fragment

Count

30% Sim. Training Neighbors Count

Reliability

assessment

bis(2-(2-(2-butoxyethoxy)ethoxy)ethyl) adipate

NEGATIVE

0.00

13

1

RELIABLE

Applicant's summary and conclusion

Conclusions:
The targets bis(2-(2-(2-butoxyethoxy)ethoxy)ethyl) adipate was predicted negative and the predictions is reliable

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