Rumen Metabolism of Senecio Pyrrolizidine Alkaloids May Explain Why Cattle Tolerate Higher Doses Than Monogastric Species.

Rumen metabolism of Senecio pyrrolizidine alkaloids (PAs) and their N-oxide forms was studied by mass spectrometry in in vitro batch culture incubates and confirmed in in vivo samples. Most N-oxides were found to undergo rapid conversion to their corresponding free bases, followed by biotransformation to metabolites hydrogenated at both the necine base and the necic acid moiety. Therefore, rumen metabolism can be considered a detoxification step, as saturated necine base structures are known as the platyphylline type, which is regarded as less or nontoxic. Individual Senecio PAs, such as jacoline, are metabolized slowly during rumen fermentation. PAs that showed limited biotransformation in the rumen in this study also showed limited transformation and CYP-mediated bioactivation in the liver in other studies. This could not only explain why PAs that are comparatively metabolically stable can pass into milk but also suggest that such PAs might be considered compounds of lesser concern.

Pyrrolizidine alkaloid profiling of four Boraginaceae species from Northern Germany and implications for the analytical scope proposed for monitoring of maximum levels.

Pyrrolizidine alkaloids (PAs) and their corresponding N-oxides (PANOs) have been determined in food and feed at levels relevant for consumer health. More than 660 different PAs have been detected, but few are available as reference substances for analytical demands. In the context of the European legislation on maximum levels of PAs in food products, a defined analytical scope of 21 PAs for determination has been suggested. An expansion of the scope from 21 to 35 PAs, including 14 structural isomers, is currently under discussion. In the present study, a target screening method was established for a comprehensive characterisation of PA profiles of the species Echium vulgare, Heliotropium europaeum, Cynoglossum officinale and Symphytum spp. to assess whether an expansion of the analytical scope is required to quantitatively cover the total PA contents of Boraginaceae species. The scope of the method comprised known and unknown PAs previously screened and confirmed in the respective plant extracts. A total of 176 PAs and PANOs were detected. The toxic 1,2-unsaturated PAs represent the predominant PA type with about 98% of the mean total content. This PA profiling demonstrates that an expansion of the scope from 21 to 35 PAs is required to adequately cover the mean total PA contents of Cynoglossum officinale and H. europaeum, whereas in the case of Symphytum spp. and Echium vulgare an expansion would not be necessary. ABBREVIATIONS: Pyrrolizidine alkaloid: PA, Pyrrolizidine alkaloid N-oxide: PANO, European Food Safety Authority: EFSA, German Federal Institute for Risk Assessment: BfR, ultra-high performance liquid chromatography: UHPLC, high-resolution: HR, tandem mass spectrometer: MS/MS, multiple reaction monitoring: MRM, data-independent MS2: ddms2, electrospray ionisation: ESI, limit of detection: LOD, limit of quantification: LOQ, gas chromatography coupled with mass spectrometry: GC-MS, fragmentation (data): MS2 (data), full scan: MS1, variable data-independent acquisition: vDIA, monoester esterified with a necic acid at position C9 of the necine base: O9-monoester, relative proportion: rel. prop., intraperitoneal: i.p., intravenous: i.v., higher-energy C-trap dissociation: HCD, all-ion fragmentation: AIF, parallel reaction monitoring: PRM.

[Persistent organic contaminants in food : Exposure, hazard potential, and health assessment]. / Persistente organische Kontaminanten in Lebensmitteln : Exposition, Gefährdungspotenzial und gesundheitliche Bewertung.

Environmental emissions of organic contaminants are caused by man-made and natural combustion processes, industrial production facilities, and the release from products. Food represents the main source of human exposure for some of these compounds. This is the case for three groups of persistent organic contaminants: (1) per- and polyfluoroalkyl substances (PFAS), (2) polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and for (3) polycyclic aromatic hydrocarbons (PAHs). The issues regarding PCDD/F emissions were already recognized as a problem in the 1970s and have since then been effectively regulated; the impact of PFAS as global anthropogenic environmental contaminants was identified much later.A system of toxicity equivalency factors (TEF system) was established for the assessment of the toxic potency of a mixed exposure to PCDD/F and certain PCBs. For the health assessment and regulation of PAHs and PFAS, no such system has been implemented so far. For PFAS, a re-evaluation of the present tolerable daily intake values (TDI values) is currently being discussed, as new insights into toxicology and epidemiology have been gained.The persistence in the environment of the compound groups discussed here leads to entry into the food chain over long periods of time, even if access into the environment is minimized. This requires a long-term continuation of the monitoring of food stuffs and forward-looking risk assessment approaches and regulatory measures.

Novel whole-cell antibiotic biosensors for compound discovery.

Cells containing reporters which are specifically induced via selected promoters are used in pharmaceutical drug discovery and in environmental biology. They are used in screening for novel drug candidates and in the detection of bioactive compounds in environmental samples. In this study, we generated and validated a set of five Bacillus subtilis promoters fused to the firefly luciferase reporter gene suitable for cell-based screening, enabling the as yet most-comprehensive high-throughput diagnosis of antibiotic interference in the major biosynthetic pathways of bacteria: the biosynthesis of DNA by the yorB promoter, of RNA by the yvgS promoter, of proteins by the yheI promoter, of the cell wall by the ypuA promoter, and of fatty acids by the fabHB promoter. The reporter cells mainly represent novel antibiotic biosensors compatible with high-throughput screening. We validated the strains by developing screens with a set of 14,000 pure natural products, representing a source of highly diverse chemical entities, many of them with antibiotic activity (6% with anti-Bacillus subtilis activity of