Endocrine properties of biocidal substances

The assessment of endocrine-disrupting properties under the Biocidal Products Regulation (BPR) is proving to be hugely challenging. Already in the past, a clear evaluation of endocrine-disrupting properties was difficult due to the different modes of action in different organisms and partly inconclusive test systems. 

Effects on the hormonal system

Endocrine disruptors (EDs) have the potential to interfere with the natural hormonal system of humans and animals and thus to impair health and development. The ways in which a substance disrupts the hormonal system are manifold and can be difficult to prove. An ED assessment consists in determining a substance’s estrogenic, androgenic, thyroidal and steroidogenic modes of action (EATS).

An essential and challenging element of this assessment is the establishing of a plausible biological link between endocrine activity and a harmful effect. In many cases, the disruption is not immediately apparent and only becomes evident upon chronic exposure or even in subsequent generations. Another problem with EDs is that they are often effective in very low concentrations and additive effects can occur with EDs that are already present in the environment. As hormonal systems vary substantially across different species, a substance that is not an ED in mammals may, for e. g., trigger significant effects in other species, such as fish and insects.

ED assessment is delaying regulatory processes

All biocidal active substances that were still in the review programme for existing active substances up to 2018 must be assessed in accordance with the specific criteria given in “Guidance for the identification of endocrine disruptors in the context of Regulations (EU) No 528/2012 and (EC) No 1107/2009” in order that a decision may be reached on their endocrine-disrupting effects. However, ambiguous specifications and a diffuse data situation have meant that this addition to the ongoing review programme has delayed approvals of biocidal active substances. So far, just 42 % of all biocidal active ingredients have been fully reviewed, even though the review programme is scheduled for completion in 2024. Since the ED assessment was introduced, 31 active substances have been reviewed by the Biocidal Products Committee. For 19 of them, there was insufficient data available to allow a decision to be reached on their ED status.

Apart from a review of the active substances, submissions for approval of a biocidal product must be accompanied by an ED assessment of all the co-formulants – regardless of their concentration in the product. This requirement, too, is problematic for the assessment, because manufacturers of biocidal products do not always know the full composition of every component.

No conclusive assessments

Since the introduction of the ED assessment, final decisions have not been reached on a whole series of biocidal active substances, despite extensive studies. A current example is afforded by two formaldehyde-releasing active substances for in-can preservatives (PT 6). The Austrian authority responsible for conducting the ED assessment based it on the data available for formaldehyde, but was unable to reach a final decision. Due to the numerous toxic properties of formaldehyde (including: H314 “Causes severe skin burns and eye damage”; H341 “Suspected of causing genetic defects”; H350 “May cause cancer”), which are already evident at low concentrations, it was not possible to identify a secondary endocrine mode of action distinct from the other known toxic modes of action and to prove it beyond doubt. What is more, formaldehyde is part of natural metabolism and so is also present in the organism, independently of its use as a biocidal agent. The dosage of formaldehyde must, for example, be low enough not to trigger the known non-endocrinal modes of action, yet high enough to be distinguishable from endogenous concentrations. This is a major problem, especially for aquatic environments, e. g. fish studies.

In the case of the two active substances mentioned above, the ED assessment could not serve as a basis for determining if the exclusion criteria of Article 5 of the BPR were met. For formaldehyde, this point is already met by other toxic properties. How other processes deal with ambiguous ED assessment outcomes still needs clarification.

Learn from experience

Our understanding of the significance of endocrine disruptors for human health and the environment has made great strides as a result of extensive research in recent years. The EU’s push to separately classify substances’ endocrine-disrupting properties in the future should therefore be seen as an important step towards the safer handling of chemicals. Yet the introduction of the ED assessment into an ongoing regulatory process in 2018 has brought with it enormous delays and problems in the approval of biocidal active substances and the authorisation of biocidal products. When the labelling of endocrine-disrupting substances is introduced in the course of CLP adaptation, it is therefore imperative we learn from the ECHA’s and the Commission’s experience with the biocidal ED assessment. Clear specifications are the only way to prevent approvals of biocidal active substances and authorisations of biocidal products from being held up in the future.