Cumulative Exposure Assessment of Triazole Pesticides

In the EFSA opinion on identification of new approaches to assess cumulative and synergistic risks from pesticides to human health a tiered approach for cumulative risk assessment has been proposed. The first tier is a deterministic approach using average and large portion consumption statistics. The higher tiers include probabilistic exposure assessment and Benchmark Dose (BMD) modeling. The aim of this study is to demonstrate the feasibility and applicability of a higher tier assessment of cumulative exposure using probabilistic modeling in combination with the relative potency factor (RPF) approach. The RPFs are used to weigh the toxicity of each pesticide relative to the toxicity of a chosen index compound (pesticide). In this report the authors address both the short-term and long-term cumulative exposure to triazoles using different statistical model

Distinctive Cytokines as Biomarkers Predicting Fatal Outcome of Severe Staphylococcus aureus Bacteremia in Mice

Invasive Staphylococcus aureus infections are frequently associated with bacteraemia. To support clinical decisions on antibiotic therapy, there is an urgent need for reliable markers as predictors of infection outcome. In the present study in mice, bacteraemia was established by intravenous inoculation of a clinical S. aureus isolate at the LD50 inoculum. As potential biomarkers for fatal outcome, blood culture (qualitative and quantitative), serum levels of C-reactive protein (CRP), as well as 31 selected cytokines and chemokines were assessed during the first three days of infection. A positive S. aureus blood culture, the quantitative blood culture, CRP levels, and levels of eight cytokines were indicative for the presence of S. aureus bacteraemia. However, only tumor necrosis factor (TNF) α, interleukin (IL) 1α, and keratinocyte chemoattractant (KC; a functional homologue of human IL-8) were each significantly elevated in eventually non-surviving infected mice versus eventually surviving infected mice. In severe S. aureus bacteraemia in mice, TNF-α, IL-1α, and KC are biomarkers predicting fatal outcome of infection. KC was a biomarker elevated irrespective the progression of infection, which is very interesting regarding clinical application in view of the heterogeneity of patients experiencing bacteraemia in this respect