34The pathogenic spirochete Borrelia burgdorferi senses and responds to diverse environmental 35 challenges, including changes in nutrient availability, throughout its enzootic cycle in Ixodes 36 spp. ticks and vertebrate hosts. This study examined the role of DnaK suppressor protein (DksA) 37 in the transcriptional response of B. burgdorferi to starvation. Wild-type and dksA mutant B. 38 burgdorferi strains were subjected to starvation by shifting mid-logarithmic phase cultures 39 grown in BSK II medium to serum-free RPMI medium for 6 h under microaerobic conditions (5% 40 CO2, 3% O2). Microarray analyses of wild-type B. burgdorferi revealed that genes encoding 41 flagellar components, ribosomal proteins, and DNA replication machinery were downregulated 42 in response to starvation. DksA mediated transcriptomic responses to starvation in B. 43 burgdorferi as the dksA-deficient strain differentially expressed only 47 genes in response to 44 starvation compared to the 500 genes differentially expressed in wild-type strains. Consistent 45 with a role for DksA in the starvation response of B. burgdorferi, fewer CFUs were observed for 46 dksA mutant after prolonged starvation in RPMI medium compared to wild-type B. burgdorferi. 47 60 regulatory activity impacts B. burgdorferi metabolism, virulence gene expression, and the ability 61

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Dermal absorption is a critical element in the risk assessment of plant protection products (pesticide formulations) for operators, workers, bystanders and residents. The current EU guidance on evaluating the dermal absorption for plant protection products was last revised in 2004. Experience gained from evaluations performed using the guidance has shown that interpretation of dermal absorption data remains one of the least harmonized aspects of the risk assessment process. It is therefore necessary to review the guidance document to ensure it is contemporary and useful.Following a consultation exercise, literature review and analysis of data from dermal absorption studies a proposal for a revised guidance document has been prepared. Additional guidance has been provided on many aspects but particularly: tape stripping and residual material at the application site; reading across between formulations; approaches to adopt when there are no data on the product being evaluated; performing studies in a more consistent manner. Interpretation of tape stripping data from studies with different absorption profiles;Default values for concentrated products (25%) and in-use dilutions (100%) independent of physical chemical properties;Reading across between formulations should only be performed when the formulations are similar -criteria on similarity are provided;The most appropriate data for routine use are those obtained in vitro from human skin samples;Currently, the use of in silico approaches (e.g. (Q) SAR) to dermal absorption is not recommended.This guidance is intended to be used by notifiers, test facilities and Member States on critical aspects related to the setting of dermal absorption values to be used in risk assessments of plant protection products.

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