Ecotoxicological risk assessment for plant protection products with multiple actives substances
Introduction
The purpose of this document is to outline for applicants of CRD’s ecotoxicology risk assessment requirements for plant protection product applications containing more than one active substance (combined risk assessments for aquatic organisms, birds and mammals).
From 1st April 2012, CRD will expect all relevant product applications to contain the appropriate aquatic and /or combined bird and mammal risk assessments. For the majority of applications CRD do not require new data - a reasoned case is sufficient.
Background
As part of the authorisation process (under both Directive 91/414 and now Regulation 1107/2009), the risk to non-target organisms from the product is considered. When a product contains more than one active substance it is necessary to consider any potential additive effects of the active substances present in the product and the influence of any co-formulants. Whilst this has always been a requirement under 91/414/EC and 1107/2009, CRD have not systematically requested applicants to include such an assessment with their applications.
In the case of products containing one or more active substances, the acute or short-term risk is usually assessed via the use of formulation studies. Further information on when data are required on the formulation or product can be found in the CRD formulation guidance.
As regards long-term/reproductive risk from products it is considered unlikely that the active substance and all the co-formulants will remain intact and hence that the long-term/reproductive risk will primarily come from the active substance(s). For clarity, the approach for aquatic life and birds/mammals is discussed further below.
Aquatic life
Currently, the long-term risk to aquatic life from products that contain more than one active substance is assessed using data on the individual active substances. This is based on the assumption that the formulation will break down into its component active substances once it enters the water, i.e. the two active substances will have different fate and behaviour profiles.
It should be noted that if the product contains more than one active substance and the route of entry is via drainflowthen the potential additive effects should be considered. Similarly if the active substance and metabolite(s) are likely to co-occur then this risk should also be considered. It should be noted that the fate and behaviour of the individual active substances will determine the degree of co-occurrence and should be considered in the risk assessment. In addition, it should be considered whether the risk is being driven by one active substance. If all the active substances within the formulation pass the risk assessment with a margin of safety then the need for further assessment will be limited.
Birds and mammals
When a product has more than one active substance, the risks to birds and mammals must also be considered. Active substances may cause the same toxic effects within test organisms. In such cases a combined assessment is required for acute and long-term effects on birds and mammals. Applicants should note that this is relevant for all formulation types i.e. seed treatments, granules and foliar sprays.
The Environmental Panel (meeting108) has proposed the following tiered approach to bird and mammal risk assessments as follows:
Is one active substance clearly driving the risk assessment?
Does the Tier I risk assessment for all active substances within the formulation pass with a margin of safety?
Did the mammalian toxicology assessment identify that a combined assessment was not required?
If the answer to any of these is yes, a combined risk assessment is probably not required and a reasoned case should be presented. Otherwise, further consideration of combined risk is required.
Guidance
If a combined risk assessment is required:
The acute risk assessment can be performed using the Finney equation, as outlined in the CRD formulation guidance.
For the long-term risk assessment, CRD will apply the recommendations of Appendix B of EFSA (2009) which uses a toxic unit approach for the Tier I formulation assessment. If the Tier I risk assessment fails then further refinements will be required. Refinements may involve the standard ecological refinements outlined in EFSA (2009) or may be based on a toxicological argument. N.B. CRD do not consider it necessary to conduct additional toxicity studies when making these refinements.
Applicants are welcome to contact CRD to discuss possible refinement options (e.g. risk characterisation of each active substance, phase-specific approach (Appendix J of EFSA (2009)) on a case-by-case basis.