How Safe Are Your Co-Formulants?

Ensuring regulatory compliance and product safety in plant protection products and biocides

Co-formulants are added to plant protection products (PPPs) and biocides to enhance physical and chemical properties such as stability, emulsifiability, suspensibility, and dispersibility. While they do not contribute directly to pesticidal or biocidal activity, they can significantly influence the overall safety profile of a product due to intrinsic hazards such as acute toxicity, skin sensitization, endocrine disruption, or carcinogenicity. 

Historically, regulatory focus has centered on active substances. However, recent changes in legislation and regulatory expectations mean that co-formulants are now subject to detailed scrutiny. Their hazard classifications can affect the entire product's classification, labeling, and marketability — with some co-formulants considered unacceptable in PPPs in the EU (EU Reg. 2023/574) and others unacceptable for specific use cases if exposure cannot be mitigated by personal protective equipment (PPE). This can lead to products not being fully authorized or not authorized for particular uses that may be critical to the market. 

Why it matters

Whether you're developing a new formulation or renewing an existing product, understanding the role and risk of co-formulants is no longer optional — it is essential. Regulatory expectations are evolving, and the consequences of overlooking co-formulant safety can be significant. By proactively managing co-formulant risks, stakeholders can: 

• Avoid costly delays and reformulations
• Support smoother regulatory approvals
• Protect your product's marketability and reputation

The regulatory landscape

In the European Union, co-formulants are governed by several key regulations:

• Regulation (EC) No 1107/2009: Requires safety assessments of all product components, including co-formulants.
• Regulation (EU) 2021/383 and 2023/574: Introduces Annex III, listing unacceptable co-formulants based on toxicological and ecotoxicological concerns.
• REACH (Regulation EC 1907/2006): Mandates registration and safety data for substances manufactured or imported above specific thresholds.

These regulations require a comprehensive understanding of the toxicological and ecotoxicological profiles of co-formulants. Data can be sourced from safety data sheets, REACH dossiers, and other regulatory evaluations — both within and outside the EU — to support a complete and compliant submission. Notably, lack of data is not necessarily assumed to mean a lack of toxicity in the calculation of mixture toxicity.

Impacts on product classification

Under CLP Regulation (EC No 1272/2008), the hazard classification of a PPP or biocidal product is determined by the classifications of all its components. The classification of co-formulants can trigger classification of the entire product, depending on the identified hazard and its concentration within the product. These classifications influence risk assessments, mitigation measures, and ultimately, the acceptability and approval of the product.

In addition to carcinogenicity, mutagenicity, and reproduction (CMR) hazards, which receive the most regulatory scrutiny, skin sensitization is a growing concern. Even low concentrations of known sensitizers (>1% or substance-specific concentration limit) can result in a product being classified as a skin sensitizer. This can affect authorization, particularly for amateur uses where the use of PPE may not be considered acceptable. 

Additionally, new CLP hazard classes — such as endocrine disruption — must be considered. While these hazards may have been assessed for active substances, they may not have been evaluated for co-formulants. This gap can pose significant risks during product renewal, causing previously unforeseen regulatory challenges.

Unacceptable co-formulants

Some hazard classifications such as skin sensitization may be acceptable below particular concentration limits or by putting risk mitigation measures in place, but more severe classifications are not acceptable in co-formulants at any concentration. These hazard classifications are excluded under criteria in Regulation 574/2023, with such substances flagged for potential inclusion in Annex III, meaning they may be subject to phase-out. Co-formulants that meet criteria for inclusion in Annex III include persistence, bioaccumulation, toxicity, endocrine disruption, and CLP classification as CMR or aquatic toxicants.

Products containing these co-formulants will also not be authorized or receive authorization renewal, making proactive review essential. Importantly, the list of unacceptable co-formulants is growing each year, requiring manufacturers to keep track of potential additions. 

Harmonization and collaboration

Member States and the European Food Safety Authority (EFSA) are working to harmonize co-formulant assessments across the EU. National authorities evaluate co-formulants during product authorization, considering both EU-wide and local data. Harmonization efforts aim to ensure consistency, transparency, and protection of human health and the environment.

Strategic risk management

Effective risk management begins early in the product development process. Waiting until the end of the regulatory pathway to assess co-formulant hazards can lead to delays, costly reformulations, or non-approval.

Co-formulant hazards and supplier safety data sheets should be assessed at the outset and at regular intervals. Monitoring regulatory updates and upcoming harmonized classifications can help applicants stay ahead of potential issues. For some co-formulants, it may be advisable to proactively perform quantitative risk assessments in anticipation of more detailed risk evaluations to support regulatory compliance.