Incorporating the joint toxicity of co‐applied pesticides into the ecological risk assessment process

Abstract

Pesticides are frequently formulated as mixtures of active ingredients. Although traditionally ecological risk assessments (ERAs) have focused on individual active ingredients, there is an ongoing effort in many jurisdictions to more formally include assessment of mixtures. The overall goal of this project was to describe an approach for conducting ERA of jointly applied pesticides. We suggest that standard testing of formulation mixtures is not warranted due to the low probability of synergy occurring at a high-enough magnitude to be measurable above experimental variability. Thus, empirical testing should focus on formulations for which there is a greater likelihood of synergy due to known toxicological interactions of the pesticide class or a priori knowledge of synergy, such as intellectual property claims. Additionally, empirical testing should focus on species that are above levels of concern and limit testing on species for which it is unlikely that synergy would significantly change the outcome of the ERA. If empirical testing is warranted, we suggest that results be compared to the concentration addition model (CA). If the empirical data deviates from the model by a factor of greater than 5, then synergy is considered likely and the ERA is based on the empirical data. Otherwise, the ERA may use CA to calculate risk quotients or be based on the most toxic active ingredient. To evaluate the approach, we reviewed formulation mixtures for which data were available. Only 3 of 24 mixture studies were found to deviate from CA by more than 5. The majority of the studies had a single component that dominated toxicity, suggesting that the ERA for these formulations will not be meaningfully different if based on the most toxic active ingredient. Overall, this approach balances risk assessment conservatism and reduces testing that would likely not result in improvement of the ERA. Integr Environ Assess Manag 2018;14:79-91. C 2017 SETAC

Monarch Butterfly (Danaus plexippus) Life‐Stage Risks from Foliar and Seed‐Treatment Insecticides

“…Toxicity to mixtures of insecticides and/or other pesticides in foliar tank mixes or seed‐treatment formulations can be assessed through the use of concentration– or response–addition models (National Research Council 2013). Synergistic effects that might considerably increase toxicity would not be captured by these models, but they are relatively rare (Cedergreen 2014; Belden and Brain 2018). Olaya‐Arenas et al (2020) did not find any synergistic effects on survival when they chronically exposed larvae to milkweed leaves that were treated with a mixture of clothianidin, 2 herbicides, and 3 fungicides.…”

Assessing the Potential for Interaction in Insecticidal Activity Between MON 87751 × MON 87701 Produced by Conventional Breeding

“…This is important because potency estimates (i.e., LC 50 values) are not biological constants (Casarett et al 2003). Recently, Belden and Brain (2018) concluded that difference between predicted and observed values that are less than five-fold are not indicative of a GTA interaction and this five-fold criterion is consistent with guidance from the European Food Protection Agency (EFSA) that considers a less than five-fold difference not indicative of a significant interaction (EFSA 2013). This five-fold criterion was re-emphasized in EFSA’s recent draft guidance on mixtures testing and assessment for microbial and biological pesticides (EFSA 2018).…”

Risk assessment for pesticide mixtures on aquatic ecosystems in China: a proposed framework

“…As discussed, compared with the IA model, the CA model is, in general, more conservative, yet with similar overall accuracy in prediction . Therefore, for this assessment scheme, the well‐established CA model is considered as an appropriate model to characterize hazards for a conservative Tier‐1 assessment, even though the CA model is conceptually devoted to only similarly acting components in a mixture.…”

“…Refinement options of effects for single active ingredients can also be used for mixtures, such as geometric mean calculation, species sensitivity distribution (SSD) analysis, consideration of co‐formulant toxicity, and higher tier ecosystem studies . PNEC and RQ values of individual active ingredients can be calculated separately with different uncertainty factors.…”

“…For biocidal products, the European Chemicals Agency (ECHA) has published guidance using such comparisons to indicate potential synergistic or antagonistic effects . An acceptable magnitude of deviation, an MDR of 5, was also proposed based on a 100% coefficient of variation and a 95% level of likelihood . If the MDR values are below 5, then the CA model applies since the additive mode of action can be assumed.…”