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The foliar wash‐off coefficient is a parameter used by environmental fate models to estimate the amount of chemical removed from leaf surfaces by rainfall. In the European Union it is used by FOCUS surface water models to estimate soil loadings following rainfall after leaf surfaces have been treated with plant protection products. Currently, a default value of 0.5/cm is assumed for this parameter, although there is provision to provide experimental data to replace this default. The European Food Safety Authority proposed to increase the default parameter value to 1.0/cm. This increases the need for experimental refinement studies. However, no guidance for a harmonized protocol exists to estimate this parameter. We describe the results of a ring‐test conducted to start a process of developing a harmonized experimental protocol to measure the foliar wash‐off parameters, conducted by several laboratories across Europe. The proposed design uses whole plants (rather than individual leaves) to retain as much realism as possible. The extent of wash‐off is then determined by comparison of compound residues in two sets of plants (with and without a defined rainfall event) measured using a fully validated crop residue method. This initial ring test used tebuconazole (Folicur EW 250) sprayed at 100 g ai/ha onto tomato plants at BBCH25. Each laboratory measured the residues before and after a rainfall event of 20 mm/h for 1 h and calculated the percentage of wash‐off from these data. There was good agreement across the eight participating laboratories with a mean percentage of wash‐off of 66.8% and a 95% confidence interval of ±11.8%. Determination of robust wash‐off parameters was therefore considered feasible using the proposed test design. Environ Toxicol Chem 2023;42:535–541. © 2022 SETAC [ABSTRACT FROM AUTHOR]

Antivirulence agents targeting endospore-transmitted Clostridioides difficile infections are urgently needed. C. difficile- specific DNA adenine methyltransferase (CamA) is required for efficient sporulation and affects persistence in the colon. The active site of CamA is conserved and closely resembles those of hundreds of related S -adenosyl-l-methionine (SAM)-dependent methyltransferases, which makes the design of selective inhibitors more challenging. We explored the solvent-exposed edge of the SAM adenosine moiety and systematically designed 42 analogs of adenosine carrying substituents at the C6-amino group (N6) of adenosine. We compare the inhibitory properties and binding affinity of these diverse compounds and present the crystal structures of CamA in complex with 14 of them in the presence of substrate DNA. The most potent of these inhibitors, compound 39 (IC 50 ∼ 0.4 μM and K D ∼ 0.2 μM), is selective for CamA against closely related bacterial and mammalian DNA and RNA adenine methyltransferases, protein lysine and arginine methyltransferases, and human adenosine receptors.