ECHA Advises Read-Across Know-How, Only 'Last Resort' Animal Testing

ECHA's progress report on REACH evaluations conducted in 2015 identifies priority targets in its compliance checks and common shortcomings in registrants' dossiers. With new animal testing under the microscope, the agency provides guidance on using (Q)SARs to fill data gaps, as well as insight into its approach to assessing read-across, to assist companies readying for the May 31, 2018 registration deadline.

Firms preparing dossiers for the final phase-in deadline under the EU's Registration, Evaluation, Authorization and Restriction of Chemicals regulation may be able to fill data gaps using read-across and (Q)SARs, as well as new animal testing, but there are specifications for use of the former techniques and the latter is under increased scrutiny.

The European Chemicals Agency's latest progress report for evaluations performed on REACH dossiers in 2015 provides insight into industry compliance and recommendations for improvement as the May 31, 2018 registration deadline for existing (phase-in) chemicals draws closer.

The deadline pertains to companies that manufacture or import chemicals in the EU in volumes of 1 ton to 100 tons annually, and ECHA expects the tonnage band to account for the largest number of REACH registrations yet.

According to its website, an estimated 70,000 registrations could be submitted, covering up to 25,000 substances, which ECHA says is three times more than the submission load for either the 2010 or 2013 deadline for substances produced or imported in greater volumes. The 2010 deadline also required registration of the most hazardous known substances.

A greater proportion of ECHA's dossier compliance checks identified data deficiencies in 2015 compared with the prior year, but the agency attributes the increase to the targeted strategy it has adopted to zero in on priorities.

ECHA additionally expects the 2013 phase-in deadline to impact a greater percentage of inexperienced and small and medium-sized enterprises.

To enable such companies to prepare and organize with co-registrants "undisturbed," the agency announced March 2 that it will freeze guidance updates on registration requirements beginning May 31 of this year, pledging to break the moratorium only in rare cases over the two-year period leading up to the registration deadline.

Prospective registrants can take cues from ECHA's previous evaluation reports, which have identified shortcomings in chemical dossiers related to substance identification and faulty adaptations to standard testing protocol (Also see "ECHA’s 2013 Report Targets Advice To Low-Tonnage REACH Registrants" - HBW Insight, 3 Apr, 2014.).

The latest update, based on 2015 evaluations, hits many of the same notes, and according to the report, the proportion of compliance checks resulting in calls for additional information increased in 2015.

However, ECHA Executive Director Geert Dancet stresses in the foreword to the report that "this increase should not be interpreted as an indication of the overall quality of the registration database, but instead reflects the improved efficiency of the selection process in targeting the right substances with the right tools."

ECHA began using an updated strategy in 2015 for conducting compliance checks that focuses on "substances that matter most for the protection of people and the environment," rather than evaluating dossiers purely at random.

Strategic screening enables the agency to zero in on priority targets, including high-tonnage registrations with data gaps in human or environmental health endpoints and with high potential for exposure, for example.

For sake of transparency and predictability, ECHA publishes a regularly updated list of substances potentially subject to compliance checks.

More Data Needed In 82% Of Compliance Checks

In 2015, the agency performed 183 compliance-check evaluations. Of those, 33 (18%) were concluded with no further action, and 150 (82%) led to a draft decision indicating areas where additional data were needed.

Again, ECHA notes that "since the selection criteria are intended to find cases with high potential for compliance issues and only a small portion are selected randomly, these figures cannot be taken to indicate the overall quality of the whole registration database."

The majority of draft decisions led to decisions, following opportunities for registrants to comment and update their dossiers. Non-compliances most commonly related to substance identification and composition, Chemical Safety Report-based issues, pre-natal developmental toxicity and effects on terrestrial organisms, ECHA says.

To assist registrants subject to the 2018 deadline, ECHA held a webinar March 2 titled "Get Organized with Your Co-Registrants – SIEF Management and Data Sharing," which can be viewed in its entirety on YouTube.

The agency also considered 184 animal-testing proposals in 2015. Under REACH, registrants are required to consult ECHA before undertaking animal testing, with opportunities built into the process for third parties to submit relevant, scientifically valid information that could render the testing unnecessary.

ECHA issued draft decisions for 76% of the proposals it evaluated. With a draft decision, the agency either accepts the proposal, accepts with modifications to proposed testing conditions, accepts or rejects while requiring one or more additional tests, or rejects the proposal outright.

The remainder either were withdrawn or deemed inadmissible.

ECHA notes that it has evaluated 81% of the testing proposals submitted against the 2013 REACH deadline and is on track to complete the rest by June 1, as mandated by law.

Registrants may be required to provide a rationale for proposed animal testing, including the alternative methods they considered as a means of generating safety data without animal use, which ECHA has begun publishing as part of the third-party consultation, according to the report.

The move is in line with a December 2014 decision from the European Ombudsman that found "ECHA's interpretation of its obligations was excessively restrictive" to that point regarding animal-testing proposals and REACH's "last resort" principle (Also see "ECHA May Be Stickler In 2018 For ‘Last Resort’ Animal Tests Only" - HBW Insight, 5 Mar, 2015.).

The European Ombudsman got involved following a PETA UK complaint.

Animal Testing On ECHA's Radar

The purpose of compliance checks is to evaluate substance identity descriptions and safety information in REACH dossiers, typically on a targeted basis. ECHA is obligated to check 5% of dossiers submitted under the terms of REACH, which entered into force in June 2007.

Following the European Ombudsman decision, the agency increasingly is viewing the compliance check as an opportunity to gauge registrants' efforts to avoid animal testing and instead leverage existing data and alternative testing methods to satisfy data needs.

PETA suggested in its complaint that animal tests previously were being carried out without approval through the proposal process, while others were being carried “despite advice from ECHA that certain screening tests could be omitted if proposals were made for more extensive testing."

In its progress report, ECHA advises future registrants, as well as existing registrants considering updates to their dossiers, to:

• Actively explore all possibilities to use already existing information and alternative methods in meeting information requirements. Keep records to show your considerations.
• Remember that the REACH annexes are applied sequentially. Therefore, Annex VII requirements for in vitro irritation testing should be fulfilled before considering the Annex VIII in vivo test methods.

Further, the agency urges companies to keep in mind that "the obligation to share data applies to any registrant under the REACH Regulation irrespective of the phase-in or non-phase-in status of their substance. Consequently, potential registrants of the same substance must collaborate to share the requested information and agree on the data to be submitted jointly."

Data-sharing under REACH is seen as critical to keeping animal testing to a minimum, among other efficiencies.

In a March 1 release, ECHA notes that May 2018 registrants must determine whether their substances are already registered under earlier REACH deadlines, in which case the preparatory work is likely completed and they can contact the relevant Substance Information Exchange Forum to be part of its joint submission, negotiating access to data and cost-sharing details.

If no registration currently exists, co-registrants are responsible for organizing a new SIEF and agreeing on practical ways of working together, ECHA says, underscoring that it will not accept registrations where data has "obviously" not been shared.

ECHA held a webinar March 2 titled "Get Organized with Your Co-Registrants – SIEF Management and Data Sharing," which can be viewed in its entirety on YouTube.

Finally, ECHA notes in its report that "testing proposal consultations provide an opportunity for submission of any valid information that may address the hazard endpoint(s) in question and may make animal testing unnecessary."

Read-Across, (Q)SAR Resources Available

Use of grouping, read-across and (quantitative) structure-activity relationships represent adaptations to standard testing required under REACH, but they can serve to fill data gaps in lieu of new animal testing if certain conditions are met, ECHA says.

In its progress report, the agency directs registrants to its Read-Across Assessment Framework for toxicological properties, published in May 2015.

Read-across can enable users to predict the safety of one substance based on testing outcomes on a substance with similar properties within an established group. However, there are criteria for using the approach under REACH.

ECHA notes, for example, that while source and target substances must be structurally similar to employ read-across, that alone is not sufficient justification for predictions. A read-across hypothesis also must be provided, establishing a rationale for predictions based on structural commonalities as well as differences.

"The aim of the RAAF is to provide a transparent and structured approach to the scientific evaluation of read-across justifications made by registrants in their dossiers. The publication of this framework should help registrants to assess the quality of their own read-across cases by presenting the scientific aspects that ECHA considers to be crucial in read-across approaches," ECHA says.

The agency also announced March 17 that it has updated its Practical Guide on using and reporting (Q)SARs, theoretical models used to predict the physico-chemical, biological and environmental fate properties of compounds based on their chemical structure, according to the document.

The update expands the guide with "practical examples on how to check the reliability of QSAR predictions from some of the most commonly used QSAR software," as well as "instructions on how to check that the conditions for adapting standard testing (Annex XI to REACH) are met," ECHA says.