Inhalation and dermal exposure to biocidal products during foam and spray applications.

OBJECTIVES: Foaming and spraying are common application techniques for biocidal products. In the past, inhalation and dermal exposure during spraying have been investigated extensively. Currently, however, no exposure data are available for foaming, hindering a reliable risk assessment for foam applications of biocidal products. The focus of this project was the quantification of inhalation and potential dermal exposure to non-volatile active substances during the foam application of biocidal products in occupational settings. In some settings, exposure during spray application was measured for comparative purposes. METHODS: The inhalation and dermal exposure of operators were investigated during the application of benzalkonium chlorides and pyrethroids by foaming and spraying, considering both small- and large-scale application devices. Inhalation exposure was measured by personal air sampling; potential dermal exposure was measured using coveralls and gloves. RESULTS: Potential dermal exposure was substantially higher than inhalation exposure. Changing from spraying to foaming reduced inhalation exposure to airborne non-volatile active substances, but had no relevant effect on potential dermal exposure. However, for potential dermal exposure, considerable differences were observed between the application device categories. CONCLUSIONS: To our knowledge, this study presents the first comparative exposure data for the foam and spray application of biocidal products in occupational settings with detailed contextual information. The results indicate a reduction of inhalation exposure with foam application compared to spray application. However, special attention is necessary for dermal exposure, which is not reduced by this intervention.

Aerosol formation during foam application of non-volatile biocidal substances.

The application of biocidal products by foam is considered an alternative to droplet spraying when disinfecting surfaces or fighting infestations. Inhalation exposure to aerosols containing the biocidal substances cannot be ruled out during foaming. In contrast to droplet spraying, very little is known about aerosol source strength during foaming. In this study, the formation of inhalable aerosols was quantified according to the aerosol release fractions of the active substance. The aerosol release fraction is defined as the mass of active substance transferred into inhalable airborne particles during foaming, normalised to the total amount of active substance released through the foam nozzle. Aerosol release fractions were measured in control chamber experiments where common foaming technologies were operated according to their typical conditions of use. These investigations include foams generated mechanically by actively mixing air with a foaming liquid as well as systems that use a blowing agent for foam formation. The values of the aerosol release fraction ranged from 3.4 × 10-6 to 5.7 × 10-3 (average values). For foaming processes based on mixing air and the foaming liquid, the release fractions could be correlated to the process and foam parameters such as foam exit velocity, nozzle dimensions, and foam expansion ratio.

Prenatal developmental toxicity studies on fumes from oxidised asphalt (OA) in the rat.

The prenatal developmental toxicity of the fumes of oxidised asphalt (OA) was tested by nose-only inhalation in the rat. The test material was generated by collecting fumes from the headspace of storage tanks filled with OA. The composition of these fumes was matched to fumes sampled at a workplace where the same OA was applied in a pour-and-roll operation, representing occupational exposure with high concentrations of fumes to not underestimate the possible hazard. In the main study, dams were exposed to 0, 53, 158 and 536 mg/m3 of fume (as total organic mass), for 6 h/day for 19 days p.c. The maternal NOAEC was 53 mg/m³ (lowest dose tested). In the high-dose group treatment-related effects on body weight gain were seen. In the mid- and high-dose groups treatment-related effects on food consumption, lung weights, and histopathological changes in lungs and the upper respiratory tract were observed. The NOAEC for prenatal developmental toxicity was 536 mg/m³ since no exposure-related effects were found in any of the exposure groups for any of the investigated reproductive endpoints. Furthermore, nose-only exposure to OA fumes in concentrations up to 536 mg/m³ from days 1-19 p.c. did not induce any significant fetal abnormalities.

Prenatal developmental toxicity studies on fumes from bitumen in the rat.

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.

Occupational Exposure to Antibiotics in Poultry Feeding Farms.

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.

A mouse model for intellectual disability caused by mutations in the X-linked 2'­O­methyltransferase Ftsj1 gene.

Mutations in the X chromosomal tRNA 2'­O­methyltransferase 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.

HIF1α modulates cell fate reprogramming through early glycolytic shift and upregulation of PDK1-3 and PKM2.

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.

Functional analysis of centrosomal kinase substrates in Drosophila melanogaster reveals a new function of the nuclear envelope component otefin in cell cycle progression.

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 CkIIß. 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.