Assessment of co-formulants in PPPs
Assessment of co-formulants in PPPs
In Art. 27 of the Regulation 1107/2009 are described the criteria for a co-formulant to be unacceptable for use in PPPs. The list of unacceptable co-formulants has been bublished in COM Regulation (EU) 2021/383(https://eur-lex.europa.eu/eli/reg/2021/383/oj). Following that COM published Commission Regulation (EU) 2023/574 (https://eur-lex.europa.eu/eli/reg_impl/2023/574/oj) setting up the rules for the identification of unacceptable co-formulants.
EFSA collected data on co‐formulants contained in plant protection product (PPP) formulations for representative uses as part of applications for approval or renewal of active substances, to collate the information available during the peer review process. Information was extracted from pesticide active substances dossiers for which a peer review output was issued between January 2019 and March 2022, in which a total of 182 co‐formulants were found. EFSA published a report (https://www.efsa.europa.eu/en/supporting/pub/en-7547) which is currently under review.
About one year ago concerns were raised by MSs and discussions started about the safety of co-formulants used in PPPs as a general issue. The concerns are based among others to the following issues:
- Problem to know the full composition of the co-formulant that can be a mixture in case the applicant is not the owner of the co-formulant
- Equivalence assessment not harmonised among MSs i.e. definition not clear enough and interpretation of equivalent/alternative co-formulant may be different depending on the country
- Combined toxicity e.g. additive, synergistic or antagonistic effects
- Lack of harmonisation regarding the acute toxicity data for the formulation to be (or not) requested by MSs
- Lack of long-term toxicity data
- Incomplete data for the complete co-formulants identification (e.g., polymers, co-formulants without CAS number, UVCB[1]) and breakdown products of co-formulants
- Problem of accessibility of information on the toxicological hazard on co-formulants
- Lack of data sharing between Member States when a co-formulant is present in different PPP
- Lack of guidance in assessing alternative co-formulants
- Lack of guidance in assessing possible interactions between components (active substance, co-formulants, etc.) present in the PPP (e.g. synergist effects, metabolic activity of co-formulant versus the active substance in the PPP, etc.)
- Classification: Difficulty in assessing co-formulants when no ECHA harmonised classification (CLH) is available on the ECHA website, or, when several divergent notified classifications are established by the applicant(s) in different Safety Data Sheet (SDS)
- Analytical methods – what kind of methods are needed with respect to co-formulants/PPPs?
- SDS – quality issues
- Confidentiality makes sharing data difficult
- Applicants may not have the data on the co-formulants (especially if the co-formulant is a mixture). The data owner may refuse to provide the information
- Possible effects on terrestrial non target organisms. REACH asks data on terrestrial to be assessed, but this is often missing in dossier for co-formulants
- Data provided in the Safety Data Sheet (SDS) by manufactures is getting more and more scarce. Same SDS in different languages does not contain the same information + different CAS number sometimes for the same “substance”
- when an applicant proposes a change in the formulation composition, it is difficult to know whether the formulation change has an impact on the risk assessment/toxicity
- etc…..
Way forward in the assessment of co-formulants
Based on the information made available so far it seems that there is a general consensus among the COM, EFSA and MSs on the following actions to be taken in short and medium term:
- To ask for the complete (100% of the composition) composition of the formulation. Requirement for the supplier to submit to the Rapporteur Member State (RMS) the complete composition of co-formulants that are mixtures
- Database to be built to avoid requesting the same information to the suppliers and to share the information among MSs. Create a database to share information on individual co-formulant i.e. identity, tox and ecotox data. Build a positive list of co-formulants that are fully tested. Establish lists of co-formulants with issues and without issues to simplify the assessment process. Register full composition of PPPs and components in a common EU database
- Current SANCO Guidance document (minor & major changes in the formulation and equivalence) to be updated. Guidance Document to be developed describing the data to be requested could be drafted
- Develop a screening approach comparing the toxicity of the active substance alone and formulated
- To revise the draft review Report template to include two different parts C: one for the RMS only and one for the applicant(s)
- Part C of registration report for PPPs and volume 4 of the Draft Assessment Report (DAR) or Renewal Assessment Report (RAR) for active substances to be processed separately (not to share confidential data)
- To apply a safety factor when interactions between components are demonstrated
- To set reference values for the PPP in order to conclude on the safe use of the PPP
- To disregard the notified classifications from companies and to consider only the CLH classification if available
- Develop guidance on when it is possible to extrapolate from one formulation to another (bridging statements)
- More cooperation with ECHA for better SDS sheets
- Develop a tiered approach to determine what data are needed and how they can be efficiently assessed; use non-animal test methods, predictions such as QSAR, and a combination of data and computer models to generate new information where needed
- Apply in silico methods to understand the degradation and formation of products of different toxicity. Use in vitro tests. Establish monitoring for problematic co-formulants
Concluding remarks
Following the ZAPID workshop held on 5-7 December 2023 in Braunschweig, Germany we expect quite a lot of actions to be undertaken at EU and zonal level with regard to the assessment of co-formulants. Our suggestions are:
- To discuss asap with your suppliers of co-formulants of the above actions and to alert them to be ready to generate the necessary data
- In case they are not willing to cooperate try to identify alternative sources that have the capacities and willingness to invest keeping in mind that to switch from one source of co-formulant to another most likely will trigger an equivalence assessment
- SDSs of co-formulants should not be older than 1 year and should follow the latest version of the “Guidance on the compilation of safety data sheets” (https://echa.europa.eu/documents/10162/2324906/sds_en.pdf/01c29e23-2cbe-49c0-aca7-72f22e101e20) and Commission Regulation (EU) 2020/878 (https://eur-lex.europa.eu/eli/reg/2020/878/oj)
[1] Unknown or Variable Composition, Complex Reaction Products and Biological Materials