Water treatment – Why is it a regulatory challenge for plant protection products in the EU?

Regulation (EC) No 1107/2009 ^[1] lays down the rules for the authorisation of plant protection products in Europe with the aim of protecting humans and the environment. It is known that during primary disinfection processes for central water treatment (e.g. ozonation, chlorination) certain active substances included in plant protection products and their metabolites have the potential to form unwanted by-products with e.g. toxic, carcinogenic and genotoxic characteristics.

Notwithstanding that the EFSA (European Food Safety Authority), the scientific advisory body of the European Commission, has recently identified data gaps during the approval process of active substances, water treatment processes have not (yet) been implemented in the European data requirements (Reg. 283/2013 ^[2] or 284/2013 ^[3]) relevant for the authorisation of plant protection products. Further, no guidance document for experimental testing is available. With this information pending, addressing water treatment processes successfully becomes a challenge for applicants of plant protection products.

The data gap identified by EFSA arises from Article 4 (approval criteria for active substances) 3(b) of Regulation (EC) No 1107/2009, according to which applicants are requested to submit relevant information:

    3. A plant protection product, consequent on application consistent with good plant protection practice and having regard to realistic conditions of use, shall meet the following requirements:

    (b) it shall have no immediate or delayed harmful effect on human health, including that of vulnerable groups, or animal health, directly or through drinking water (taking into account substances resulting from water treatment), food, feed or air, or consequences in the workplace or through other indirect effects, taking into account known cumulative and synergistic effects where the scientific methods accepted by the Authority to assess such effects are available; or on groundwater; …

Central water treatment processes and regulatory relevance

Applied methods for water treatment differ across European countries, based on raw water quality and origin ^[4]. Amongst these methods, used individually or in combination, ozonation and chlorination are the main regulatory-relevant treatment processes. Undesired by-products formed from these operations could e.g. be nitrosamines or chlorinated compounds.

Applied ways of addressing ozonation and chlorination

Applicants seek to address the issue in their dossiers to authorities in different ways:

- Providing laboratory studies,
- Using theoretical approaches based on either chemical structure and expected reactions with ozone and chlorine from literature examples or calculations via quantum chemistry,
- Discussing concentrations at raw water abstraction points, or
- Simply ignoring it, as no guidance is currently in force.


How successful are current attempts to address ozonation and chlorination?

The results of an evaluation of 49 EFSA conclusions for AIR3 active substances that became available up until April 2018 are summarised in FIGURE 1. The number of attempts addressing water treatment processes during EU active substance approval successfully or not was evaluated. In FIGURE 1 successful attempts (i.e. no data gap) are displayed on the left. Attempts resulting in a data gap are shown on the right.


FIGURE 1: Evaluation of attempts to address water treatment processes for AIR3 active substances from EFSA conclusions available up until April 2018

Of the 49 active substances evaluated, only 12 applications did not have a data gap, of these 7 applications addressed the issue successfully while 5 did not address the topic at all.

However, there were 37 active substances that had a data gap, of which 18 applications waived or ignored the topic and 19 applications could not address the topic successfully.

What is the current EU position, what advice can be given to applicants?

The European Commission states that the applicant shall submit the (confirmatory) information to the European Commission, the Member States and EFSA within two years after adoption of a guidance document on evaluation of the effect of water treatment processes on the nature of residues present in surface- and groundwater.

While the guidance document is not in place, applicants have the choice for their active substance dossiers to (I) not address the issue at all, as data waiving does not result in non-approval, or to (II) try to avoid the data gap and potential request for confirmatory data by addressing the issue on EU level alongside the submission.

Recent developments and outlook

Currently water treatment is only addressed at active substance level. It remains largely unclear how the topic can be approached for product registrations and how metabolites can be realistically addressed.

The development of a guidance document is gaining speed this autumn: EFSA and several Member States are working on a scoping document to complete a previous UK guidance draft. It is intended to share the outcome on Member State level for further commenting and discussion of the next steps by end of the year ^[5].

With the implementation of such a guidance document it can be expected that other chemical sectors, e.g. industrial chemicals or pharmaceuticals, would also need to set a spotlight on the topic.

Acknowledgement
We would like to thank Jennifer Wilbuer and Martin Geisthardt for their kind support with the statistical evaluation.

References
[1] Regulation (EC) No 1107/2009 of the European Parliament and of the Council of 21 October 2009, 24.11.2009, concerning the placing of plant protection products on the market and repealing Council Directives 79/117/EEC and 91/414/EEC.
[2] Commission Regulation (EU) No 283/2013 of 1 March 2013, 3.4.2013, setting out the data requirements for active substances, in accordance with Regulation (EC) No 1107/2009 of the European Parliament and of the Council concerning the placing of plant protection products on the market.
[3] Commission Regulation (EU) No 284/2013 of 1 March 2013, 3.4.2013, setting out the data requirements for active substances, in accordance with Regulation (EC) No 1107/2009 of the European Parliament and of the Council concerning the placing of plant protection products on the market.
[4] WHO (2011): Guidelines for drinking-water quality - 4th ed., ISBN 978 92 4 154815 1.
[5] EFSA (2018): Network on Pesticide Steering meeting minutes of the 23rd meeting, Parma (12-13 June 2018).

Authors:
Sabine Dorn and Frauke Schnitzler
knoell Germany GmbH | Konrad-Zuse-Ring 25 | 68163 Mannheim | Germany | www.knoell.com
Contact us: sadorn@knoell.com and fschnitzler@knoell.com