Combined risk assessments for pesticide registration in Great Britain and Northern Ireland

When you are applying for pesticide registration in Great Britain or Northern Ireland for a product which contains more than one active substance, you need to consider any potential additive effects of the active substances present. Similarly, you need to consider additive effects if the active substance and one or more of its ecotoxicologically relevant metabolite(s) are likely to co-occur in any environmental compartment. This is carried out through a combined risk assessment where the risk is not addressed by consideration of the formulated product.

This guidance explains when a combined risk assessment is necessary and how to carry out that assessment for higher tier drainflow. This section does not address the risk from the product formulation.

For calculation of formulation PEC (predicted environmental concentrations) values in other environmental compartments refer to Soil assessment for pesticide registration in Great Britain and Northern Ireland and Spray drift surface water exposure assessments for pesticide registration in Great Britain and Northern Ireland.

Combined risk assessments in the soil compartment
Combined risk assessments in the groundwater compartment
Combined risk assessment in the surface water compartment
Combined first tier drainflow assessment
Combined higher tier drainflow assessment

Combined risk assessments in the soil compartment

You do not need to provide a combined risk assessment for soil as this will fall within the risk assessment of the formulated product except in the following situations:

when the active substances produce a common metabolite that also triggers a soil risk assessment (typically a metabolite listed as an ecotoxicologically relevant). The sum of the initial PECsoil values for the metabolite from each active substance provides a combined PECsoil value for the metabolite. This assessment is conservative because it assumes the maximum formation of the metabolite from each active substance occurs at the same time
when one or both of the active substances requires an accumulation assessment, the PECsoil accumulation values for each active substance will provide the necessary input values for any additional combined assessment required

For calculation of formulation PEC values in other environmental compartments refer to Soil assessment for pesticide registration in Great Britain and Northern Ireland.

Combined risk assessments in the groundwater compartment

A combined assessment for groundwater is only necessary if the active substances produce a common metabolite. The PECgw values for the common metabolite from each active substance are summed for each groundwater scenario to produce combined PEC_gw values. This assessment is conservative because it assumes the 80th percentile annual average concentration of the metabolite from each active substance occurs in the same simulation year.

Further information on ground water assessment can be found at Groundwater assessment for pesticide registration in Great Britain and Northern Ireland.

Combined risk assessment in the surface water compartment

Spray drift

You do not need to provide a combined risk assessment for surface water spray drift as this will fall within the risk assessment of the formulated product except in the situations described below:

The active substances produce a common metabolite that also triggers a surface water risk assessment (typically a metabolite listed as an ecotoxicologically relevant). The initial PEC_sw or PEC_sed values for the metabolite from each active substance are summed as part of the environmental fate assessment to provide a combined PEC_sw or PEC_sed value. This assessment is conservative because it assumes the maximum formation of the metabolite from each active substance occurs at the same time
Pesticide use patterns using multiple applications that result in PEC_sw or PEC_sed values of either active substance that are greater than those from a single application. This may result in residues in the water or sediment that are greater than from a single application. Alternatively, a relatively persistent active substance may still be present in the water concurrently with a metabolite formed from another active substance. The standard PEC_sw or PEC_sed values for each component will provide the necessary input values for any additional combined assessment required
Formulation studies which address the chronic risks to fish, aquatic invertebrates, and sediment dwelling organisms are not available

Drainflow

If surface water exposure via drainflow is relevant, it is unlikely that the formulation will remain intact in drainflow. Therefore, there is no requirement to assess the combined risk from the formulation via drainflow.

The principal risk of combined exposure via drainflow will therefore be due to multiple active substances and/or ecotoxicologically relevant metabolites that may co-occur in surface water. If all the active substances within the formulation and any ecotoxicologically relevant metabolites pass the first-tier risk assessment with a margin of safety, then the need for further assessment of combined exposures and effects will be limited. This potentially complex area can also be simplified by considering whether the risk is driven by one active substance or metabolite, for example when one active substance or metabolite constitutes ≥ 90% of the combined risk (for more information refer to section 10.3.7 in Guidance on tiered risk assessment for plant protection products for aquatic organisms in edge‐of‐field surface waters).

Combined first tier drainflow assessment

For general guidance on the calculation of first tier PEC_sw and PEC_sed values from exposure via drainflow please refer to First tier drainflow calculation for pesticide registration in GB and NI.

The following approaches are for surface water exposure but could equally be applied to sediment.

The simplest way to assess the possible effects from combined exposure is to compare the sum of individual PEC_sw values with the lowest appropriate regulatory acceptable concentration (RAC) from all substances of interest (Equation 1). The risk is acceptable where the lowest RAC from all substances is greater than PEC_sw (combined, drainflow). This is also a conservative approach because it assumes all substances are as toxic as the most toxic component.

Equation 1

PEC_sw(combined , drainflow) = PEC_sw(A) + PEC_sw(B) + ....
where:PEC_sw(X) is the PEC_sw(drainflow) for substance X

If this does not result in an acceptable assessment, the Finney equation (Equation 2) can be used to refine the combined exposure in drainflow. This equation accounts for differences in toxicity and relative exposure concentrations of each substance. When using the Finney equation, it is important to use the fractions of the substances in drainflow, not the fraction in the original formulation, since the ratios of the substances in the receiving water body can change significantly as a result of drainflow. The risk is acceptable where RAC(A + B + …) is greater than PEC_sw (combined, drainflow).

Equation 2 (Finney equation)

1/RAC(A+B+...) = f(A)/RAC(A) + f(B)/RAC(B) + ....

where:

RAC(A + B + ...) is the combined regulatory acceptable concentration
RAC(X) is the regulatory acceptable concentration of substance X
f(X) is the fraction of substance X in the mixture calculated from:

f(X)=PEC_sw(X)/PEC_sw (combined, drainflow)

Consideration of ecotoxicologically relevant metabolites at first tier

If a metabolite passes the drainflow assessment at the first tier, it is not necessary to consider it further in any combined assessment. This is because at this first tier the calculated drainflow concentration is a conservative (high) value for both active substance and the metabolite(s). Since the active substance must degrade in order to generate the metabolite, it is unlikely that both substances will occur simultaneously at the same high concentrations for the purposes of a combined assessment. The conservative assumptions associated with the simple first tier calculations are enough to cover any combined risks from the substances at the lower concentrations that would occur in reality
If two or more active substances produce a common metabolite, then a combined assessment as outlined in Equation 1 is necessary. If the combined metabolites assessment passes at the first tier, then it is not necessary to include the combined metabolite concentrations in any combined active substance assessment.

Combined higher tier drainflow assessment

You will need to present a higher tier drainflow assessment if the risk from the first-tier exposure assessment is not acceptable. The MACRO model is available to carry out the higher tier drainflow assessment. For general guidance on carrying MACRO out higher tier drainflow assessments and the scenario years approach to assessing the output from the model please refer to MACRO higher tier drainflow modelling for pesticide registration in Great Britain and Northern Ireland.

Please note: The modelling tool Webfram is currently unavailable. When available the Webfram model may be suitable for use when considering combined assessments, and further details will be provided. General guidance for higher tier drainflow assessments using Webfram is given at Webfram higher tier drainflow modelling for pesticide registration in Great Britain and Northern Ireland.

MACRO

There are three options for combined exposure from higher tier drainflow modelling with MACRO. They progress in refinement from option (1) to option (3).

Option (1) Combined annual maximum concentrations and lowest RAC

Combine the annual maximum PECsw values from drainflow for each substance for each of the 30 years (Equation 1) and compare the 30 combined values against the lowest RAC value to determine the number of exceedance years. Carry out this procedure for each soil and climate combination modelled.

Option (2) Combined annual maximum concentrations and Finney equation using annual data

Determine the combined toxicity RAC value of the mixture for each of the 30 years from the Finney equation (Equation 2) using the maximum annual PECsw values from drainflow of each substance for each year. There is an exceedance year where the sum of the maximum annual PECsw values from drainflow exceeds the combined toxicity RAC value for that year. Carry out this procedure for each soil and climate combination modelled.

Option (3) Combined daily concentrations and Finney equation using daily data

Determine the combined toxicity RAC value of the mixture for each day of the 30 years from the Finney equation (Equation 2) using the daily PECsw values from drainflow of each substance. Where the sum of the daily PECsw values from drainflow for any day in a calendar year exceeds the daily combined toxicity RAC value, an exceedance year is recorded. Carry out this procedure for each soil and climate combination modelled.

The combined risk is assessed for each option using the same criteria as for a single substance as shown in MACRO higher tier drainflow modelling for pesticide registration in Great Britain and Northern Ireland.