In-silico prediction of dislodgeable foliar residues and regulatory implications for plant protection products.

BACKGROUND: When experimentally determined dislodgeable foliar residue (DFR) values are not available, regulatory agencies use conservative default DFR values as a first-tier approach to assess post-application dermal exposures to plant protection products (PPPs). These default values are based on a limited set of field studies, are very conservative, and potentially overestimate exposures from DFRs. OBJECTIVE: Use Random Forest to develop classification and regression-type ensemble models to predict DFR values after last application (DFR0) by considering experimentally-based variability due to differences in physical and chemical properties of PPPs, agronomic practices, crop type, and climatic conditions. METHODS: Random Forest algorithm was used to develop in-silico ensemble DFR0 prediction models using more than 100 DFR studies from Corteva AgriscienceTM. Several variables related to the active ingredient (a.i.) that was applied, crop, and climate conditions at the time of last application were considered as model parameters. RESULTS: The proposed ensemble models demonstrated 98% prediction accuracy that if a DFR0 is predicted to be less than the European Food Safety Authority (EFSA) default DFR0 value of 3 µg/cm2/kg a.i./ha, it is highly indicative that the measured DFR value will be less than the default if the study is conducted. If a value is predicted to be larger than or equal to the EFSA default, the model has an 83% prediction accuracy. IMPACT STATEMENT: This manuscript is expected to have significant impact globally as it provides: A framework for incorporating in silico DFR data into worker exposure assessment, A roadmap for a tiered approach for conducting re-entry exposure assessment, and A proof of concept for using existing DFR data to provide a read-across framework that can easily be harmonized across all regulatory agencies to provide more robust assessments for PPP exposures.

A comparison between field measurements of vapour concentrations of plant protection products and predictions by the BROWSE model.

A database of field measurements of air concentrations of pesticide active ingredients has previously been compiled by CropLife Europe with an aim to revise the default air concentration values and assumptions applied in assessing vapour exposure in the risk assessment of bystanders and residents. The BROWSE model, released in 2014, which is a regulatory risk assessment model that includes the exposure of residents and bystanders has a component relating to post-application vapour inhalation. Predictions of concentration deduced from exposures obtained using the BROWSE model were compared with field measurements of 24-h and 7-day average concentrations. The methodology for obtaining concentration estimates from the BROWSE model is described, and the criteria for including field studies in the comparison are given. The field data were adjusted to account for differences between the field experiment and the BROWSE scenario using factors derived from a separate plume dispersion model. This showed that BROWSE provides a satisfactory level of conservatism in determining potential exposures of residents and bystanders to vapour and could be a reliable alternative to replace the current EFSA approach for predicting vapour inhalation exposures for pesticides where no compound-specific data are available.

Measured air concentrations of pesticides for the estimation of exposure to vapour in European risk assessments.

There is an identified need to revise the default air concentration values and assumptions applied in assessing vapour exposure in the risk assessment of bystanders and residents to plant protection products. To address this, we evaluated inhalation exposure via vapour using previously unpublished data from 29 field and wind tunnel studies. The database comprises 35 trials with 11 active ingredients covering a wide range of scenarios with respect to vapour pressure, crops, application rates and European regions. Of the 961 individual measurements, 634 were below the Limit of Detection (LOD), 282 were between the LOD and Limit of Quantification (LOQ) and only 45 (4.7%) were quantifiable. Ten individual non-normalized samples exceeded 0.1 µg/m³. Of the 81 first-day measurements after the application, 36 were

Review of air concentrations of pesticides for estimating exposure to vapour in European risk assessments.

In current European non-dietary risk assessment for bystanders and residents, one of the plant protection product exposure pathways to be addressed is vapour inhalation. At present, active ingredients are grouped according to vapour pressure and assigned corresponding values. Risk assessments are driven by only two default air concentration values. Sampling is inconsistent, background data are sparse and many factors having an impact on air concentrations are not considered. Within the changing regulatory landscape over the last 20 years, criteria for volatility grouping and consequently for vapour exposure estimation have been applied heterogeneously. Here we review the background data currently used in the exposure assessment guidance to demonstrate the arbitrary nature of derived air concentration values and their inconsistent application in exposure assessment. In doing so we discuss air concentration from a risk assessment perspective and how active ingredients are grouped according to vapour pressure. We examine the database which at present forms the basis for predicting inhalation exposure to PPPs, particularly the two concentration levels driving risk assessments, and we discuss several other factors having an impact on air concentration. In conclusion, we recommend an urgent revision of the default air concentration values and assumptions applied in assessing vapour exposure.

Compounded conservatism in European re-entry worker risk assessment of pesticides.

We review the risk parameters and drivers in the current European Union (EU) worker risk assessment for pesticides, for example considering crop maintenance, crop inspection or harvesting activities, and show that the current approach is very conservative due to multiple worst-case default assumptions. As a case study, we compare generic exposure model estimates with measured worker re-entry exposure values which shows that external cumulative exposure is overpredicted by about 50-fold on average. For this exercise, data from 16 good laboratory practice (GLP)-compliant worker exposure studies in 6 crops were evaluated with a total number of 184 workers. As generic overprediction does not allow efficient risk management or realistic risk communication, we investigate how external exposure can be better predicted within the generic model, and outline options for possible improvements in the current methodology. We show that simply using averages achieves more meaningful exposure estimates, while still being conservative, with an average exposure overprediction of about 9-fold. Overall, EU risk assessment includes several numerically unaccounted "hidden safety factors", which means that workers are well protected; but simultaneously risk assessments are biased towards failing due to compounded conservatism. This should be considered for further global or regional guidance developments and performing more exposure-relevant risk assessment.