Aerotoxic Syndrome: A New Occupational Disease?

Background: Concerns related to adverse health effects experienced by aircrew exposed to aircraft contaminated air have been ongoing for over 6 decades. Unfiltered breathing air is supplied to the cabin via the engine compressor. The likelihood that oil leaking over the engine oil seals may enter the cabin air supply has prompted continuing debate about the hazards associated with exposure to neurotoxic substances and to the thermally degraded or pyrolysed mixture. In this study, we undertook an in-depth investigation of aircrew involved in suspected aircraft contaminated air events.  Methods: Two studies were conducted to review the circumstances and symptoms of a cohort of aircrew working in the pressurized air environment of aircraft. A table of effects was then used for categorizing symptoms and reviewing other sources of data related to aircraft fluids and selected other conditions.  Results: Both acute and chronic exposures to neurotoxic and a wide range of thermally degraded substances were confirmed, along with a clear pattern of acute and chronic adverse effects. The latter were supported by medical findings and diagnoses, notably involving the neurological, neurobehavioural and respiratory systems.  Conclusion: A clear cause and effect relationship has been identified linking the symptoms, diagnoses and findings to the occupational environment. Recognition of this new occupational disorder and a clear medical investigation protocol are urgently needed

Modeling the Dietary Pesticide Exposures of Young Children

A stepped approach was used to assess the exposures of 1 1/2 – 4 1/2-year-old children in the United Kingdom to residues of pesticides (dithiocarbamates; phosmet; carbendazim) found in apples and pears. The theoretical possibility that the acute reference dose (ARD) was being exceeded for a particular pesticide/fruit was tested by applying a combination of maximal variability and maximum measured residue relative to an average-body-weight consumer. The actual risk was then quantified by stochastically modeling consumption, from dietary survey data, with individual body weights, against published residue results for 2000–2002 and the variability of residue distribution within batches. The results, expressed as numbers of children per day likely to ingest more than the ARD, were in the range of 10–226.6 children per day, depending upon the pesticide and year of sampling. The implications for regulatory action are discussed

Modelling the comet assay.

Abstract The single-cell gel electrophoresis technique or comet assay is widely regarded as a quick and reliable method of analysing DNA damage in individual cells. It has a proven track record from the fields of biomonitoring to nutritional studies. The assay operates by subjecting cells that are fixed in agarose to high salt and detergent lysis, thus removing all the cellular content except the DNA. By relaxing the DNA in an alkaline buffer, strands containing breaks are released from supercoiling. Upon electrophoresis, these strands are pulled out into the agarose, forming a tail which, when stained with a fluorescent dye, can be analysed by fluorescence microscopy. The intensity of this tail reflects the amount of DNA damage sustained. Despite being such an established and widely used assay, there are still many aspects of the comet assay which are not fully understood. The present review looks at how the comet assay is being used, and highlights some of its limitations. The protocol itself varies among laboratories, so results from similar studies may vary. Given such discrepancies, it would be attractive to break the assay into components to generate a mathematical model to investigate specific parameters. The technique The single-cell gel electrophoresis assay has been used for over 20 years to assess DNA damage. The assay is able to measure both single-and double-strand breaks with versatility and sensitivity The comet technique has been adapted over the years into different protocols such as the alkaline and neutral versions which were thought to discriminate between double-and single-strand breaks. This theory was revealed by Collins et al. [1] at the most recent International Comet Assay conference to be a misconception as alkaline conditions are not specific to detecting single-strand breaks. FISH (fluorescent in situ hybridization) techniques were also adapted for application to the comet where the DNA probe can be hybridized to a specific gene sequence or even to a whole chromosom

Is a Cumulative Exposure to a Background Aerosol of Nanoparticles Part of the Causal Mechanism of Aerotoxic Syndrome?

We present strong evidence for the presence of aerosols of Nano-particles (also termed Ultrafine Particles (UFPs) in aerosol science) in the breathing air of commercial aircraft using engine bleed air architecture. The physical and chemical nature of engine oils and the high temperatures attained in aircraft jet engines (up to 1700°C in the oil circulation and up to 30,000°C in the bearings) explain why UFPs are to be expected. A discussion of oil seals used in gas turbine engines concludes that they will permit UFPs to cross them and enter the breathing air supply, in conjunction with a complex mixture of chemicals such triaryl phosphates which are neurotoxic. A consideration of the toxicology of Nano-particles concludes that their continual presence over a typical working lifetime of up to 20,000 hours in aircrew will predispose them to chronic respiratory problems and will exacerbate the translocation of neurotoxic substances across the blood brain barrier

Is a Cumulative Exposure to a Background Aerosol of Nanoparticles Part of the Causal Mechanism of Aerotoxic Syndrome?

We present strong evidence for the presence of aerosols of Nano-particles (also termed Ultrafine Particles (UFPs) in aerosol science) in the breathing air of commercial aircraft using engine bleed air architecture. The physical and chemical nature of engine oils and the high temperatures attained in aircraft jet engines (up to 1700°C in the oil circulation and up to 30,000°C in the bearings) explain why UFPs are to be expected. A discussion of oil seals used in gas turbine engines concludes that they will permit UFPs to cross them and enter the breathing air supply, in conjunction with a complex mixture of chemicals such triaryl phosphates which are neurotoxic. A consideration of the toxicology of Nano-particles concludes that their continual presence over a typical working lifetime of up to 20,000 hours in aircrew will predispose them to chronic respiratory problems and will exacerbate the translocation of neurotoxic substances across the blood brain barrier

From single cells to tissues: interactions between the matrix and human breast cells in real time.

International audienceMammary gland morphogenesis involves ductal elongation, branching, and budding. All of these processes are mediated by stroma--epithelium interactions. Biomechanical factors, such as matrix stiffness, have been established as important factors in these interactions. For example, epithelial cells fail to form normal acinar structures in vitro in 3D gels that exceed the stiffness of a normal mammary gland. Additionally, heterogeneity in the spatial distribution of acini and ducts within individual collagen gels suggests that local organization of the matrix may guide morphogenesis. Here, we quantified the effects of both bulk material stiffness and local collagen fiber arrangement on epithelial morphogenesis. The formation of ducts and acini from single cells and the reorganization of the collagen fiber network were quantified using time-lapse confocal microscopy. MCF10A cells organized the surrounding collagen fibers during the first twelve hours after seeding. Collagen fiber density and alignment relative to the epithelial surface significantly increased within the first twelve hours and were a major influence in the shaping of the mammary epithelium. The addition of Matrigel to the collagen fiber network impaired cell-mediated reorganization of the matrix and increased the probability of spheroidal acini rather than branching ducts. The mechanical anisotropy created by regions of highly aligned collagen fibers facilitated elongation and branching, which was significantly correlated with fiber organization. In contrast, changes in bulk stiffness were not a strong predictor of this epithelial morphology. Localized regions of collagen fiber alignment are required for ductal elongation and branching suggesting the importance of local mechanical anisotropy in mammary epithelial morphogenesis. Similar principles may govern the morphology of branching and budding in other tissues and organs

Synergistic interaction between commonly used food additives in a developmental neurotoxicity test

Exposure to non-nutritional food additives during the critical development window has been implicated in the induction and severity of behavioral disorders such as attention deficit hyperactivity disorder (ADHD). Although the use of single food additives at their regulated concentrations is believed to be relatively safe in terms of neuronal development, their combined effects remain unclear. We therefore examined the neurotoxic effects of four common food additives in combinations of two (Brilliant Blue and L-glutamic acid, Quinoline Yellow and aspartame) to assess potential interactions. Mouse NB2a neuroblastoma cells were induced to differentiate and grow neurites in the presence of additives. After 24 h, cells were fixed and stained and neurite length measured by light microscopy with computerized image analysis. Neurotoxicity was measured as an inhibition of neurite outgrowth. Two independent models were used to analyze combination effects: effect additivity and dose additivity. Significant synergy was observed between combinations of Brilliant Blue with L-glutamic acid, and Quinoline Yellow with aspartame, in both models. Involvement of N-methyl-D-aspartate (NMDA) receptors in food additive-induced neurite inhibition was assessed with a NMDA antagonist, CNS-1102. L-glutamic acid-and aspartameinduced neurotoxicity was reduced in the presence of CNS-1102; however, the antagonist did not prevent food color-induced neurotoxicity. Theoretical exposure to additives was calculated based on analysis of content in foodstuff, and estimated percentage absorption from the gut. Inhibition of neurite outgrowth was found at concentrations of additives theoretically achievable in plasma by ingestion of a typical snack and drink. In addition, Trypan Blue dye exclusion was used to evaluate the cellular toxicity of food additives on cell viability of NB2a cells; both combinations had a straightforward additive effect on cytotoxicity. These data have implications for the cellular effects of common chemical entities ingested individually and in combination