REACH – Applications for authorisation AFA020-01 OPEO

Overview

Public consultation on alternatives

Reference: AFA020-01

Applicant: Abbott Laboratories Limited

Application type: Initial

Substance name: 4-(1,1,3,3 tetramethylbutyl)phenol, ethoxylated (4-tert-OPnEO))

EC number:  -

CAS number: 9002-93-1 / 9036-19-5

Proposed use: Professional use as a surfactant, in Wash Buffer components used in conjunction with Fluorescence in Situ Hybridisation (FISH) test kits and/or their Laboratory Developed Test (LDT) equivalents, in clinical diagnostic use for medical analysis of human tissue and blood samples to identify characteristic genetic abnormalities related to specific disease conditions.

Broad information on use applied for (conditions of use and function): The Applicant is importing and distributing FISH assay IVD test kits to its professional end users (medical institutions, academic centres, hospitals, laboratories, etc.) in Great Britain (GB). The Applicant is applying on behalf of its GB customers for the end use of the wash buffer as a component of the IVD kit, which may include preparation of wash buffers at end user sites using 4-tert-OPnEO supplied as a kit component. The Applicant currently provides approximately 400 assay types for the GB market.

Fluorescence In Situ Hybridisation (FISH) is a technique that allows the visualisation of specific nucleic acid sequences within a cellular preparation. The Applicant’s FISH assays kits are used for detecting genetic abnormalities, which may include changes in gene and/or chromosome copy number, deletions, translocations and other rearrangements. FISH assay kits are widely utilised in oncology, as well as prenatal and postnatal genetic screening. FISH results may be used to support treatment decisions, such as patient stratification into presumed responder/non-responder groups to determine suitability for prescription of approved therapies; or enrolment in clinical trials, where no approved therapy currently exists.

Technical function:

The FISH method requires a process of probe application, hybridisation, post hybridisation wash (using a wash buffer containing 4-tert-OPnEO), counterstain and then examination. The 4-tert-OPnEO serves solely as a surfactant in the applicant’s products (within the wash buffer). 4-tert-OPnEO performs five parallel functions within this wash buffer as follows:

• reduces nonspecific interactions between a FISH probe and the specimen matrix;
• reduces nonspecific interactions between FISH probe and off-target DNA sequences;
• prevents binding, leading to aggregation on slide target or coverslip surfaces,
• prevents self-aggregation and/or co-aggregation of FISH probe with proteins, thus minimising fluorescence background and/or specificity issues and,
• promotes solubility and therefore efficient removal of unbound FISH probe material during washes, thus allowing specific hybridisation to be detected after washing. Any alternative(s) to the use of 4-tert-OPnEO in FISH wash buffer would be required to provide an equivalent set of functions to ensure the optimal wash effectiveness of the specimens and to ensure accurate interpretation of results of patient specimens across its wide range of molecular diagnostic products.

Key substance properties of 4-tert-OPnEO that allow the system solutions to function according to requirements include: surfactant classification (non-ionic); Hydrophile-Lipophile Balance; surface tension; and cloud point.

The professional laboratory technicians use the wash buffer in low volumes in both the manual or the automated preparation of specimen loaded microscope slides by placing the slides in the wash buffer at two concentrations 0.3% and 0.1% 4-tert-OPnEO to allow for sufficient washing. Slides are assessed after washing under a fluorescent microscope. As the interpretation is qualitative, the ability of the technician to adequately interpret the results is dependent upon the efficiency of the washing process including the wash buffer.

List of descriptors:

• Sector of end use (SU): 20 
• Product category: 21 – Laboratory chemicals
• Environmental release category (ERC): 8a 
• Article category related to subsequent service life (AC): N/A

Technical Function: Surfactant 

Annual tonnage used:  0 – 0.1 Tonne per year

Review period requested: 7.5 years

How to submit comments

Provide some basic information on possible alternative(s) in the online survey below but more detailed information should be provided in document(s) prepared using the commenting templates in the related section below. A “public version” should always be completed and will be published after the consultation has closed. If you want to include confidential information in your submission, please additionally complete a “confidential version” and submit both versions as attachments.

The consultation lasts for 8 weeks (unless otherwise specified) and closes at 23:59 London time (BST).