Endocrine disruptor (ED) testing has gained importance for chemical companies since 2018 with the introduction of EFSA and ECHA guidance for agrochemicals and biocides. With discussions ongoing around thyroid adversity and the potential neurotoxicological impact, agrochemical and biocide manufacturers have been under increased pressure, which has further complicated the initial registration or renewal of biocides and pesticides.
Chemical companies are awaiting confirmation on the anticipated addition of endocrine disruptor hazard categories firstly to CLP (classification, labelling, and packaging) as well as an update of the information requirements for REACH (registration, evaluation, authorisation, and restriction of chemicals) regulations, causing further uncertainty around data requirements.
What Could This Mean for Chemical Companies?
With the delay of hazard classes and REACH amendments, chemical manufacturers are faced with difficult questions, such as:
- What testing will be needed for compounds that are in development, and for substances that have been registered?
- What data gaps will need addressing?
- What are the costs associated with the required testing and how long will these studies take?
- Will there be a grace period before the new requirements apply?
- Will they test in-house or outsource?
The expected demand for endocrine disruptor studies is anticipated to outstrip capacity in the short-term leading to limited study availability.
These combined factors impact budgets, timelines, revenue, and profit.
What do we Know?
In October 2020 as part of the European Green Deal, the European Commission published the chemical strategy for sustainability with the subtitle — Towards a Toxic Free Environment. Within this, they highlighted that endocrine disrupting chemicals required specific attention. They also highlighted the fragmented nature of the EU regulatory system in relation to endocrine disruptors.
The European Commission will most likely look to ensure that sufficient information is made available, in an appropriate format, to simplify endocrine disruptor identification and minimize exposure of both humans and the environment.
Dealing with Shifting Timelines
Firstly, there will be a revision or an update to the current CLP regulations to introduce hazard classes for endocrine disruption. Once these hazard classes are defined then the data requirements for industrial chemicals under REACH can be updated to address these hazards.
The updates to CLP regulations are planned for the second half of 2022, however, this date has already been moved back more than once. If the CLP changes go ahead in the third quarter of 2022, the REACH revision proposals would follow in early 2023. Since both are interlinked and clear timelines are not defined, manufacturers and developers are experiencing planning challenges.
Two proposals for additional information requirements have been presented by the European Commission adding in vitro and in vivo mechanistic studies starting at the low tonnage band requirements and expanding testing for in vivo adversity at the high tonnage bands (see Figure 1, opposite page, outlining current proposals). The chemical Strategy for Sustainability the Commission further sets out a preventive generic approach to risk management ensuring that endocrine disruptors are banned in consumer products. Although substances can already be identified as substance of very high concern (SVHC) based on endocrine disrupting properties, workers’ protection will be further strengthened by introducing endocrine disruptors as a separate category of SVHCs under REACH.
What can Companies do to Prepare?
Many manufacturers don’t have the luxury of waiting indefinitely on regulations to be finalized. To plan properly for testing budgets and to accurately estimate timelines for substance registrations, companies are looking for steps they can take now to help them prepare.
One approach that could be useful is to look at your current portfolio of existing substances to identify potential endocrine disruptor issues. Similarly, any new actives in development could be evaluated early on to identify ED risk. One solution is to use ED screening studies to gather initial data which would then allow you to prioritize your substances, both new and in development, based on potential concern.
Screening can identify where further data may be required and it can also help pinpoint where adaptations could be needed to development pipelines or where groupings can be made of existing substances to enable a read-across approach.
Endocrine Disruptor Screening
The first level of endocrine disruptor screening would employ read-across, QSARs, and/or other in silico predictions.
The next step, on identification of problematic compounds, would be to begin in-vitro studies to provide usable data. In-vitro endpoints include estrogen, androgen, and steroidogenesis (EAS) modalities. The fourth addition is T or thyroid modality.
Endocrine screening tests can be shorter in duration, use less test item and carry a lower cost than full GLP studies. This allows manufacturers to make an intelligence-led evaluation of risk without making a larger commitment to time and budget.
By screening early on, you can take a strategic approach to your testing plan. Screening can give you a more rounded view of your products. By employing good product stewardship, you are better equipped to make informed business decisions around your renewal and registration plans. You may decide to stop development of a compound which carries a high ED risk potential to save costs further down the line. You can also be proactive and prioritize crucial products where you identify additional testing requirements to fill dossier gaps.
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