Transactivation assay for detection of compounds with (anti)estrogenic potential using MELN cells

Topic: Reproductive toxicity, Endocrine disruption

Test Method Number:

TM2009-02 (EU)

Short Name of TM:

MELN

Year received:

2009

Responsible Organisation:

EURL ECVAM - European Union

General Comments:

Validation stopped after consultation with test submitter

Method Description

The MELN test is an estrogen receptor transactivation assay, assessing the activity of (anti-)estrogenic compounds.

The test is based on the human mammary adenocarcinoma cell line (MCF-7). The cells endogenously express the estrogen receptor alpha (ERα), and are stably transfected with a luciferase reporter gene. The test assesses the transcription of the luciferase gene, through the measurement of luminescence, and allows the discrimination between agonists and antagonists.

This assay investigates the potential for interaction of a chemical substance with estrogenic nuclear receptors for endogenous hormones and as such investigates early events within an adverse outcome pathway (AOP) associated with perturbation of the endocrine system. Such assay could be used within Integrated Testing Strategy (ITS) or Integrated Approaches to Testing and Assessment (IATA) for identification of endocrine disruptors.

Track Approval Status

Submission
Validation
Peer-review
Recommendation
Regulatory acceptance/Standards

Submission

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Date	Stage	Comment
Jan 2009	Receipt of presubmission	Presubmission received.
Dec 2009	Assessment of presubmission	Submitter notified of presubmission outcome. Invitation to send a full submission.
Oct 2010	Receipt of full submission	Full test submission (TST) received.
Nov 2010	Assessment finalised	Method qualified to enter a validation study coordinated by EURL ECVAM.

Validation

Show status

Date	Stage	Comment
Nov 2010	Ongoing	Start of MELN validation study coordinated by EURL ECVAM.
Apr 2013	Ongoing	Conclusion of the first phase of the study to finalise validation dataset for assessing between laboratory reproducibility. Start second the phase of the study to evaluate predictive capacity.
Nov 2014	Stopped	Validation stopped due to lack of agreement on conditions for material transfer. Notification was provided to submitter.

Peer-review

Recommendation

Regulatory acceptance/Standards