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May
09

EPA’s SAP Publishes Its Report on RNAi Pesticides

This Science Advisory Committee report explains that”[t]he focus of this SAP meeting was on the problem formulation phase of the human health and environmental risk assessment of pesticidal products using RNA interference technology (RNAi). EPA consulted with the SAP on scientific issues that might be unique to RNAi and how they could fit under the existing risk assessment framework. The SAP addressed seven charge questions divided into human health considerations (questions 1-3) and ecological risk considerations (questions 4-7). The Panel provided the following overall summary of the major conclusions and recommendations detailed in the report.”

***

“Human Health Considerations – Major Conclusions and Recommendations

The Panel agreed that bioinformatic analysis can be used to identify specific nucleotide identity in long sequences of dsRNA or processed shorter products that could bind in a siRNA-like fashion, provided the sequences are in the database and the appropriate algorithm is used. Sequence identity does not mean that the dsRNA would provoke an RNAi response, but should caution the potential for unintended interactions and further review.

The Panel agreed with EPA’s assessment that the primary route of exposure is through the oral ingestion of dsRNA PIPs in food plants or food plants treated with exogenously applied dsRNAs end- products. Dietary RNA is extensively degraded in the mammalian digestive system by a combination of ribonucleases (RNases) and acids that are likely to ensure that all structural forms of RNA are degraded throughout the digestive process. There is no convincing evidence that ingested dsRNA is absorbed from the mammalian gut in a form that causes physiologically relevant adverse effects. Evidence of any dietary uptake plant micro RNAs (miRNAs) in mammals is nominal and nonspecific.”

***

“Ecological Risk Considerations – Major Conclusions and Recommendations

Overall, the Panel agreed with the concerns raised by the EPA regarding the inadequacies of the current environmental fate and non-target effects testing frameworks for dsRNA PIPs and exogenously applied dsRNA products. Uncertainties in the potential modes of action in non-target species, potential for chronic and sublethal effects, and potential unintended consequences in the various life stages of non-target organisms are sufficient justification to question whether the current Agency framework for ecological effects testing is applicable to dsRNA PIPs or exogenously applied non-PIP end-use products. Due to the modes of action of RNAi, no one set of test species will serve as an adequate representation of non-target species for all pesticidal products using RNAi technology. The classic approach of developing and assembling effects data for a standard set of test species will likely not work well for this technology.

Current requirements for soil degradation studies will provide some insight for non-target testing, but are inadequate to address the environmental fate of dsRNA PIPs or exogenously applied dsRNA products and potential exposures to non-target organisms. The inability to predict dsRNA exposure to non-target organisms using the current non-target testing framework challenges the evaluation of potential non-target effects.

The Panel concluded that additional data are needed to reduce uncertainty in the environmental fate and ecological risk assessments; however, the task of prescribing additional tests or additional test species cannot be done without a better understanding of exposure to dsRNA PIPs or exogenously applied dsRNA products, and the RNAi modes of action.”

Click here to read the full SAP report.

 

 

 

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