Understanding Annexes VII-X

Avoiding obstacles with REACH Annexes VII-X

Posted by Dr. David Howes, Expert Consultant in Chemical Legislation and Chemistry, Covance

In the EU, the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulations address the manufacturing and import of chemicals to ensure they are safe for human health and the environment. The registration dossier outlines the standard information requirements for a substance and minimum data required that describe the physicochemical, toxicological, environmental fate and ecotoxicological properties of the substance.

With this information, the European Chemicals Agency (ECHA) can make a decision regarding the safety of the substance. However, data requirements vary with the amount of substance used. Often, more complex information is required to manufacture or import a substance into the EU and the European Economic Area (EEA).

A brief history of REACH

The information requirements for REACH evolved from the previous NONS (notification of new substances) legislation for chemical registration. REACH provides a legal framework that mandates data sharing across companies manufacturing or importing the same substance promotes the reduction of animal testing and engages more transparently with the wider public.

Understanding tonnage bands and data requirements

REACH has four tonnage bands governed by different annexes:

  • 1–10 tons/year – Annex VII
  • 10–100 tons/year – Annex VIII
  • 100–1,000 tons/year – Annex IX
  • >1,000 tons/year – Annex X

Under REACH, applicants are now required to conduct a one-generation reproductive toxicity study (OECD test guideline 443) when preparing chemical dossiers.

Annex VII

The data requirements for Annex VII are the most simple, focusing on key physicochemical properties, such as the substance’s vapor pressure, water solubility and flammability. The requirements also include assessments for short-term ecotoxicology endpoints like aquatic toxicity and biodegradation and for the toxicology endpoints of in vitro skin and eye irritation, skin corrosion and sensitization, mutagenicity and acute toxicity.

Only the latter endpoint of acute toxicity requires testing on vertebrate animals. If the case can be made for a substance in the 1-10 tons band being of low risk, then there is the benefit of reduced information requirements where only data on physicochemical properties are necessary.

Annex VIII

Annex VIII builds on the Annex VII requirements with further toxicology endpoints – some of which require in vivodata, such as short-term repeated dose studies (28 days), a reproductive/developmental toxicity screening test with further tests for mutagenicity, ecotoxicity and environmental fate.

Annex IX and X

Annexes IX and X add more complex and long-term studies for toxicology, ecotoxicology and environmental fate endpoints. Annex IX covers 90-day repeated dose, extended one generation reproductive toxicity and pre-natal development toxicity studies as well as long term aquatic toxicity, biodegradation and bioaccumulation tests. Testing on terrestrial species is introduced at this tonnage band with short-term toxicity testing on invertebrates, plants and microorganisms a requirement.

Annex IX tests further extends the testing requirements with studies for reproductive and developmental toxicity on second species, a test for carcinogenicity and long-term testing on terrestrial species.

If a substance falls under Annex IX and X requirements, then the testing already undertaken at Annex VII and VIII must be taken into account. Some tests are also driven by the outcome of the chemical safety assessment; others are performed in a tiered manner, all of which affects the testing strategy.

As for the lower tonnage bands, the use of alternative test strategies is possible for the higher tonnage bands. For example, use of read across, chemical categories, weight of evidence and quantitative structure-activity relationship (QSAR) models. However, there are fewer opportunities to use such approaches with the more complex endpoints.

More commonly, clients will need to adopt a well thought-out, logical, testing strategy to deliver the most resource and animal-efficient testing plan. Any tests involving animals at Annex IX and X cannot be conducted without first submitting a testing proposal to the European Chemicals Agency (ECHA) within a dossier. The test proposal is reviewed by the ECHA Member State Committee and decisions made available to the general public and any other interested third parties, in line with REACH’s stated aim of openness and transparency.

Key considerations for REACH

Clients should consider the following to establish the most optimal testing approach for a substance:

  • Let the science drive the testing and follow a logical and considered approach
  • Know the substance’s properties as many chemicals exhibit unique behavior
  • Be familiar with the test methods, understand their objective, methodology, outcome and potential limitations
  • Wherever possible, follow ECHA Endpoint Specific Guidance
  • Take heed of the advice in ECHA document: Application of the CLP Criteria
  • Always consider alternative methods to reduce the use of animals

Meeting REACH requirements

To successfully navigate the data requirements for different tonnage bands, clients need to have an in-depth understanding of their substance’s properties and usage, combined with expert technical and regulatory knowledge on how to meet REACH requirements.

Looking to discover more?

The last REACH deadline was in May 2018 and brought to a close the period of active information gathering on the safety of chemical products marketed in the EU/EEA. It has resulted in a massive database of safety information on a wide range of substances, and heralds an exciting new phase of evolution in scientific and regulatory thinking. With REACH submission deadlines complete, ECHA has moved into a new phase of dossier scrutiny and evaluation. What should you expect when a dossier decision letter hits your inbox? Our next blog in this series will look to address this issue.