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The overall purpose of this project was the identification and selection of relevant literature to gather information on chemical identification and characterisation, sources and occurrence in food as well as data on toxicokinetics and toxicity of mineral oil hydrocarbons in order to support the preparatory work for the human health risk assessment of this type of substances., EU; zip; feedco@efsa.europa.eu

An Extensive Literature Search (ELS) to collect and identify all studies published since 2010 and relevant to the topic mineral oil hydrocarbons in combination with the substance group characterisation, occurrence in food and toxicity was performed in the three databases PubMed, Web of Science and SciFinder® for six Areas. After combination of the searches from the three databases and removal of the duplicates, the total number of references is 2504. The evaluation of all retrieved references for relevance by screening the title and abstract and applying eligibility criteria (inclusion/exclusion) resulted in a total number of relevant references for Area 1 of 55, for Area 2 of 27, for Area 3 of 15, for Area 4 of 21 for Area 5 of 1 and for Area 6 of 6. The total number of relevant references was 93. However, for the substance group POH no relevant reference was identified. Additionally, there are 4 references additionally, which could not be clearly assigned.

The formation of acid mine drainage (AMD) and release of toxic contaminants, such as arsenic (As), is a serious environmental problem encountered worldwide. In this study, we investigate the crucial role the Klip River wetland system plays in attenuating As arising from gold mining activities within the Witwatersrand Basin in Johannesburg, South Africa. Mining operations in the region commenced over 130 years ago and have been associated with the widespread pollution of water resources by AMD. We investigated As concentrations, bioavailability and speciation in a peat core from the Klip River wetland as well as in samples from the main tributaries and tailing storage facilities (TSFs) in the upper catchment. Total As concentrations in tributary and TSFs samples ranged between 10.1 – 89.9 mg kg-1 and 77.4 – 106 mg kg-1, respectively, with concentrations in the wetland varying between 1.91 – 73.8 mg kg-1. In general, As bioavailability was low in both catchment (19%) and wetland (4%) samples, with elemental associations suggesting the majority is bound in an immobile form to organic matter and sulfide. As(v) was the predominant species detected in all samples (0.0901 – 16.6 mg kg-1), with As(iii), MMA and DMA present in lower concentrations. Strong correlations between As and S suggest that speciation and methylation are dependent on both chemical and microbial activity. The study highlights the vital role that wetlands can play in sequestering As in the environment.

An Extensive Literature Search (ELS) to collect and identify all studies published since 2009 and relevant to the topic organic arsenic in combination with the substance group characterisation, occurrence in food and toxicity was performed in the three databases PubMed, Web of Science and Scopus for eight scientific Areas. After combination of the searches from the three databases and removal of the duplicates, the total number of references was 6998. The evaluation of all retrieved references for relevance by screening the title and abstract and applying eligibility criteria (inclusion/exclusion) for group (a) small methylated arsenic species resulted in a total number of relevant references for 406 for Area 1a, 246 for Area 2a, 287 for Area 3a, 31 for Area 4a, 56 for Area 5a, 108 for Area 6a, 38 for Area 7a and 95 for Area 8a. In comparison a smaller number of relevant references was retrieved for substance group (b) arsenic species other than small methylated species and including any other organic species: 352 for Area 1b, 73 for Area 2b, 257 for Area 3b, 14 for Area 4b, 23 for Area 5b, 30 for Area 6b, 57 for Area 7b, and 18 for Area 8b. However, these were assigned to be relevant for more than one Area or substance group. All relevant references were additionally screened to extract available information at a high level by full paper review. In this step, some references were excluded due to the lack of relevant information. The total number of relevant references is further reduced to 1239.

The prenatal developmental toxicity of bitumen fume was tested by nose-only inhalation in the rat. The fumes for exposure were collected from the headspace of a storage tank filled with a bitumen corresponding in composition to an anticipated worst-case occupational exposure. The composition of these fumes was compared to actual paving site fumes to ensure its representativeness for workplace exposures. In a dose-range-finding study male and female rats were exposed to 0, 103, 480 or 1043 mg/m3 of fume (as total organic mass), for 6 h/day during 20 days post conception (p.c.). Dose-related effects on body weight and lungs were observed in the mid- and high-dose groups. In the main study, dams were exposed to 0, 52, 151 and 482 mg/m3 of fume, for 6 h/day during 19 days p.c. The maternal NOAEL was 52 mg/m³. In the high-dose group treatment-related effects on body weight (gain), food consumption, lung weights, and histopathological changes in lungs and larynx were observed. In the mid-dose group only histopathological changes in the larynx and lungs were found. The NOAEL for prenatal developmental toxicity was 151 mg/m³ based on reduced fetal weight in the high-dose group (482 mg/m³). However, these changes are most likely a consequence of the maternal toxicity, in particular the reduction of maternal body weight gain by 26 % as compared to control. Nose-only exposure to bitumen fumes in concentrations up to 482 mg/m³ from days 1-19 p.c. did not induce any significant fetal anomalies.

Today, antibiotics are essential for effective treatment of infectious diseases both in human and veterinary medicine. The increasing development and distribution of antibiotic-resistant microorganisms are subject of concern. In some sectors of animal agriculture, such as poultry feeding farms, the application of antibiotics and hence occupational exposure is inevitable. In the past, numerous studies focussed on the occurrence of antibiotic-resistant bacteria in livestock farming, but little attention was paid to the employees. The exposure of workers to antibiotics was the focus of the study detailed in this article. Four biomonitoring campaigns monitoring systemic exposure of workers to antibiotics were run at two farms over four fattening periods. Urine samples of potentially affected employees were sampled and analysed for the antibiotics of interest by liquid chromatography–mass spectrometry. The highest antibiotic concentrations detected in urine samples exceeded the minimum inhibitory concentration of some bacteria strains. In some cases, the amount of antibiotics excreted over a time-period of 24 h indicated the exceedance of the tolerable daily intake.

Mutations in the X chromosomal tRNA 2'-O-methyltransferase FTSJ1 cause intellectual disability (ID). Although the gene is ubiquitously expressed affected individuals present no consistent clinical features beyond ID. In order to study the pathological mechanism involved in the aetiology of FTSJ1 deficiency-related cognitive impairment, we generated and characterized an Ftsj1 deficient mouse line based on the gene trapped stem cell line RRD143. Apart from an impaired learning capacity these mice presented with several statistically significantly altered features related to behaviour, pain sensing, bone and energy metabolism, the immune and the hormone system as well as gene expression. These findings show that Ftsj1 deficiency in mammals is not phenotypically restricted to the brain but affects various organ systems. Re-examination of ID patients with FTSJ1 mutations from two previously reported families showed that several features observed in the mouse model were recapitulated in some of the patients. Though the clinical spectrum related to Ftsj1 deficiency in mouse and man is variable, we suggest that an increased pain threshold may be more common in patients with FTSJ1 deficiency. Our findings demonstrate novel roles for Ftsj1 in maintaining proper cellular and tissue functions in a mammalian organism.

Reprogramming somatic cells to a pluripotent state drastically reconfigures the cellular anabolic requirements, thus potentially inducing cancer-like metabolic transformation. Accordingly, we and others previously showed that somatic mitochondria and bioenergetics are extensively remodeled upon derivation of induced pluripotent stem cells (iPSCs), as the cells transit from oxidative to glycolytic metabolism. In the attempt to identify possible regulatory mechanisms underlying this metabolic restructuring, we investigated the contributing role of hypoxia-inducible factor one alpha (HIF1α), a master regulator of energy metabolism, in the induction and maintenance of pluripotency. We discovered that the ablation of HIF1α function in dermal fibroblasts dramatically hampers reprogramming efficiency, while small molecule-based activation of HIF1α significantly improves cell fate conversion. Transcriptional and bioenergetic analysis during reprogramming initiation indicated that the transduction of the four factors is sufficient to upregulate the HIF1α target pyruvate dehydrogenase kinase (PDK) one and set in motion the glycolytic shift. However, additional HIF1α activation appears critical in the early upregulation of other HIF1α-associated metabolic regulators, including PDK3 and pyruvate kinase (PK) isoform M2 (PKM2), resulting in increased glycolysis and enhanced reprogramming. Accordingly, elevated levels of PDK1, PDK3, and PKM2 and reduced PK activity could be observed in iPSCs and human embryonic stem cells in the undifferentiated state. Overall, the findings suggest that the early induction of HIF1α targets may be instrumental in iPSC derivation via the activation of a glycolytic program. These findings implicate the HIF1α pathway as an enabling regulator of cellular reprogramming. Stem Cells 2014;32:364–376

Phosphorylation is one of the key mechanisms that regulate centrosome biogenesis, spindle assembly, and cell cycle progression. However, little is known about centrosome-specific phosphorylation sites and their functional relevance. Here, we identified phosphoproteins of intact Drosophila melanogaster centrosomes and found previously unknown phosphorylation sites in known and unexpected centrosomal components. We functionally characterized phosphoproteins and integrated them into regulatory signaling networks with the 3 important mitotic kinases, cdc2, polo, and aur, as well as the kinase CkIIβ. Using a combinatorial RNA interference (RNAi) strategy, we demonstrated novel functions for P granule, nuclear envelope (NE), and nuclear proteins in centrosome duplication, maturation, and separation. Peptide microarrays confirmed phosphorylation of identified residues by centrosome-associated kinases. For a subset of phosphoproteins, we identified previously unknown centrosome and/or spindle localization via expression of tagged fusion proteins in Drosophila SL2 cells. Among those was otefin (Ote), an NE protein that we found to localize to centrosomes. Furthermore, we provide evidence that it is phosphorylated in vitro at threonine 63 (T63) through Aurora-A kinase. We propose that phosphorylation of this site plays a dual role in controlling mitotic exit when phosphorylated while dephosphorylation promotes G(2)/M transition in Drosophila SL2 cells.

The fate of flubendazole and fenbendazole in manure and manured soils was investigated under laboratory and field conditions. In pig manure, both 14 C-labeled benzimidazoles disappeared slowly. After a 102 day incubation period, extractable fractions contained 72% flubendazole or 80% fenbendazole of the radioactivity initially applied. The latter was accompanied by 4% of the corresponding metabolite fenbendazole-sulfoxide. Non-extractable residues amounted to 24 and 13%, respectively. On this basis, test manures with 7 day aged benzimidazole residues were prepared. Mobility tendencies differed for clay and sand soils as well as for standard and test-manure application. Regarding K oc > 1100 L/kg, however, criteria for potential leachers were not fulfilled. The metabolic fate of flubendazole was predominated by the occurrence of the parent compound while fenbendazole was accompanied by fenbendazole-sulfoxide. In clay soil samples after standard application, DT 50 values were 174 and 54 days, respectively. Mineralization and formation of non-extractable residues were of minor relevance. For fenbendazole, these processes were intensified after test-manure application. Due to enhanced formation of fenbendazole-sulfoxide, fenbendazole-sulfone, and non-extractable residues, DT 50 thus dropped to 9 days. Similar mobility and degradability tendencies were also found under field conditions. In the sand soil, however, the metabolic dynamics decelerated due to its lower microbial activity.