Health consequences of exposure to aircraft contaminated air and fume events: a narrative review and medical protocol for the investigation of exposed aircrew and passengers.

Thermally degraded engine oil and hydraulic fluid fumes contaminating aircraft cabin air conditioning systems have been well documented since the 1950s. Whilst organophosphates have been the main subject of interest, oil and hydraulic fumes in the air supply also contain ultrafine particles, numerous volatile organic hydrocarbons and thermally degraded products. We review the literature on the effects of fume events on aircrew health. Inhalation of these potentially toxic fumes is increasingly recognised to cause acute and long-term neurological, respiratory, cardiological and other symptoms. Cumulative exposure to regular small doses of toxic fumes is potentially damaging to health and may be exacerbated by a single higher-level exposure. Assessment is complex because of the limitations of considering the toxicity of individual substances in complex heated mixtures.There is a need for a systematic and consistent approach to diagnosis and treatment of persons who have been exposed to toxic fumes in aircraft cabins. The medical protocol presented in this paper has been written by internationally recognised experts and presents a consensus approach to the recognition, investigation and management of persons suffering from the toxic effects of inhaling thermally degraded engine oil and other fluids contaminating the air conditioning systems in aircraft, and includes actions and investigations for in-flight, immediately post-flight and late subsequent follow up.

Outdoor air pollution from industrial chemicals causing new onset of asthma or COPD: a systematic review protocol.

BACKGROUND: Until today, industrial sources contribute to the multifaceted contamination of environmental air. Exposure to air pollutants has the potential to initiate and promote asthma and chronic obstructive pulmonary disease (COPD). At global scale, both entities cause the majority of about 4 million annual deaths by respiratory disease. However, we identified industrial contamination as a subgroup of air pollution that may be associated with this burden and is underinvestigated in research. Therefore, the aim of this study is to investigate associations between substances industrially released into environmental air and the occurrence of asthma and COPD in the human population. Here we present the protocol for our systematic review of the current evidence. METHODS: The following determinations will be applied during the systematic review process and are specified in the protocol that complies with the PRISMA-P statement. Populations of children and adults, as well as outdoor workers, exposed to industrially released air pollutants are of interest. Eligible studies may include subjects as controls who are non- or less exposed to the investigated air pollutants. The outcomes new-onset asthma and/or COPD investigated with risk ratio, odds ratio, hazard ratio, incidence rate ratio, cumulative incidence, and incidence rate are eligible. We will search the electronic literature databases EMBASE, MEDLINE, and Web of Science for peer-reviewed reports of incidence studies and incidence case-control studies. After systematic sorting of initial records, included studies will be subjected to quality assessment. Data will be synthesized qualitatively and, if appropriate, quantitatively for risk ratio and odds ratio. We will maintain and provide a PRISMA report. DISCUSSION: Results of this systematic review may indicate alterations of incidence and risk of asthma and/or COPD in populations within industrial exposure radiuses including outdoor workplaces. Specific causal substances and compositions will be identified, but results will depend on the exposure assessment of the eligible studies. Our approach covers effects of industrial contributions to overall air pollution if studies reportedly attribute investigated emissions to industry. Results of this study may raise the question wether the available higher-level evidence sufficiently covers the current scale of industrial exposure scenarios and their potential harm to respiratory health. TRIAL REGISTRATION: This protocol was registered in PROSPERO, registration number CRD42020151573 .

Comparative cyto- and genotoxicity assessment of glyphosate and glyphosate-based herbicides in human peripheral white blood cells.

Glyphosate is the most heavily applied active compound of agricultural pesticides. It is solely used in more than 750 different glyphosate-based herbicide formulations (GBHs) that also contain other substances, mostly presumed as inert by regulatory agencies. The toxicity of formulations is currently assessed substance by substance, neglecting possible combined effects in mixtures and many of the findings regarding the toxic effects of glyphosate and GBHs to human cells are inconsistent. This is the first study to investigate and compare the cyto- and genotoxic potential of the active ingredient glyphosate and GBHs in human mononuclear white blood (HMWB) cells. HMWB cells were treated for 4 h at 37 °C with increasing concentrations (1-1000 µM) of glyphosate alone and in three GBHs (Roundup Mega, Fozat 480 and Glyfos) to test cytotoxic effect with fluorescent colabelling and genotoxic effect with comet assay. In addition, each concentration was tested with and without metabolic activation using human liver S9 fraction. We found that glyphosate alone does not induce significant cytotoxicity and genotoxicity over the tested concentration range. Contrarily, GBHs induced statistically significant cell death from 250 µM (Roundup Mega and Glyfos) and 500 µM (Fozat 480), as well as statistically significant increase of DNA damage from 500 µM (Roundup Mega and Glyfos) and 750 µM (Fozat 480); however, the latter observation may not be explained by direct DNA injuries, rather due to the high level of cell death (>70%) exerted by the formulations. Metabolic activation significantly increased the DNA damage levels induced by Glyfos, but not of the other GBHs and of glyphosate. The differences observed in the toxic pattern of formulations and the active principle may be attributed to the higher cytotoxic activity of other ingredients in the formulations or to the interaction of them with the active ingredient glyphosate. Hence, further investigation of formulations is crucial for assessing the true health risks of occupational and environmental exposures.

Immunological methods for diagnosis and monitoring of IgE-mediated allergy caused by industrial sensitizing agents (IMExAllergy).

Industrial sensitizing agents (allergens) in living and working environments play an important role in eliciting type 1 allergic disorders including asthma and allergic rhinitis. Successful management of allergic diseases necessitates identifying their specific causes (ie, identify the causative agent(s) and the route of contact to allergen: airborne, or skin contact) to avoid further exposure. Identification of sensitization by a sensitive and validated measurement of specific IgE is an important step in the diagnosis. However, only a limited number of environmental and occupational allergens are available on the market for use in sIgE testing. Accordingly, specific in-house testing by individual diagnostic and laboratory centers is often required. Currently, different immunological tests are in use at various diagnostic centers that often produce considerably divergent results, mostly due to lack of standardized allergen preparation and standardized procedures as well as inadequate quality control. Our review and meta-analysis exhibited satisfactory performance of sIgE detection test for most high molecular weight (HMW) allergens with a pooled sensitivity of 0.74 and specificity of 0.71. However, for low molecular weight (LMW) allergens, pooled sensitivity is generally lower (0.28) and specificity higher (0.89) than for HMW tests. Major recommendations based on the presented data include diagnostic use of sIgE to HMW allergens. A negative sIgE result for LMW agents does not exclude sensitization. In addition, the requirements for full transparency of the content of allergen preparations with details on standardization and quality control are underlined. Development of standard operating procedures for in-house sIgE assays, and clinical validation, centralized quality control and audits are emphasized. There is also a need for specialized laboratories to provide a custom service for the development of tests for the measurement of putative novel occupational allergens that are not commercially available.

Performance of specific immunoglobulin E tests for diagnosing occupational asthma: a systematic review and meta-analysis.

OBJECTIVES: To determine the test performance parameters for the retrievable range of high-molecular-weight (HMW) and low-molecular-weight (LMW) occupational allergens and to evaluate the impact of allergenic components and the implementation of measures for test validation. METHODS: A protocol with predefined objectives and inclusion criteria was the basis of an electronic literature search of MEDLINE and EMBASE (time period 1967-2016). The specific inhalation challenge and serial peak flow measurements were the reference standards for the specific IgE (sIgE) test parameters. All of the review procedures were reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: Seventy-one studies were selected, and 62 entered meta-analysis. Pooled pairs analysis indicated a sensitivity of 0.74(95% CI 0.66 to 0.80) and specificity of 0.71(95% CI 0.63 to 0.77) for HMW allergens and a sensitivity of 0.28(95% CI 0.18 to 0.40) and specificity of 0.89(95% CI 0.77 to 0.95) for LMW allergens. Component-specific analysis improved the test parameters for some allergens. Test validation was handled heterogeneously among studies. CONCLUSION: sIgE test performance is rather satisfactory for a wide range of HMW allergens with the potential for component-specific approaches, whereas sensitivity for LMW allergens is considerably lower, indicating methodological complications and/or divergent pathomechanisms. A common standard for test validation is needed.

Mercury pollution in modern times and its socio-medical consequences.

Mercury plays a critical role in serious health problems due to environmental or occupational exposures. Aquatic ecosystems are an essential component of the global biogeochemical cycle of mercury, as inorganic mercury can be converted to toxic methyl mercury in these environments and reemissions of elemental mercury rival anthropogenic mercury releases on a global scale. The history of the Minamata disease, a typical example of industrial pollution, has shown how corporate secrecy and ignorance on part of the health authorities may influence the devastating spread of environmental contamination and the progress of disease. While the Minamata Convention, in place since 2017, is aiming to lower mercury exposure and to prevent adverse effects, there are still knowledge gaps in the areas of global environmental mercury exposure. Areas of uncertainty in the global biogeochemical cycle of mercury include oxidation processes in the atmosphere, land-atmosphere and ocean-atmosphere cycling, and methylation processes in the ocean. Pollution related to climate change (especially in boreal and arctic regions), bioaccumulation and biomagnification of methyl mercury in the food chain, especially in fish and marine mammals, needs to be addressed in more detail. Information is lacking on numerous hidden contaminant exposures i.e. from globally applied traditional medicine, mercury containing skin creams and soaps, dental amalgam, ethyl mercury containing vaccines and latex paint additives, as well as on mercury releases from power plants, e-waste/fluorescent lamps, wildfire emissions, and global artisanal small-scale gold mining activities. Mercury occurs in various forms with different levels of toxicity. While much is already known and documented on the health effects of mercury, present knowledge and translation into preventive actions is still incomplete. Risks for long term health effects trough prolonged low dose exposure and trough cumulative exposures of various mercury forms should be further addressed. Preventive actions should include adequate human biomonitoring programs. Research data should be translated swiftly into management tools for local policy makers and health professionals, also paying attention at the major differences in mercury contamination across the globe.

Correction to: Health risks in international container and bulk cargo transport due to volatile toxic compounds.

[This corrects the article DOI: 10.1186/s12995-015-0059-4.].

Diagnosis, monitoring and prevention of exposure-related non-communicable diseases in the living and working environment: DiMoPEx-project is designed to determine the impacts of environmental exposure on human health.

The WHO has ranked environmental hazardous exposures in the living and working environment among the top risk factors for chronic disease mortality. Worldwide, about 40 million people die each year from noncommunicable diseases (NCDs) including cancer, diabetes, and chronic cardiovascular, neurological and lung diseases. The exposure to ambient pollution in the living and working environment is exacerbated by individual susceptibilities and lifestyle-driven factors to produce complex and complicated NCD etiologies. Research addressing the links between environmental exposure and disease prevalence is key for prevention of the pandemic increase in NCD morbidity and mortality. However, the long latency, the chronic course of some diseases and the necessity to address cumulative exposures over very long periods does mean that it is often difficult to identify causal environmental exposures. EU-funded COST Action DiMoPEx is developing new concepts for a better understanding of health-environment (including gene-environment) interactions in the etiology of NCDs. The overarching idea is to teach and train scientists and physicians to learn how to include efficient and valid exposure assessments in their research and in their clinical practice in current and future cooperative projects. DiMoPEx partners have identified some of the emerging research needs, which include the lack of evidence-based exposure data and the need for human-equivalent animal models mirroring human lifespan and low-dose cumulative exposures. Utilizing an interdisciplinary approach incorporating seven working groups, DiMoPEx will focus on aspects of air pollution with particulate matter including dust and fibers and on exposure to low doses of solvents and sensitizing agents. Biomarkers of early exposure and their associated effects as indicators of disease-derived information will be tested and standardized within individual projects. Risks arising from some NCDs, like pneumoconioses, cancers and allergies, are predictable and preventable. Consequently, preventative action could lead to decreasing disease morbidity and mortality for many of the NCDs that are of major public concern. DiMoPEx plans to catalyze and stimulate interaction of scientists with policy-makers in attacking these exposure-related diseases.

Experimental outgassing of toxic chemicals to simulate the characteristics of hazards tainting globally shipped products.

Ambient monitoring analyses may identify potential new public health hazards such as residual levels of fumigants and industrial chemicals off gassing from products and goods shipped globally. We analyzed container air with gas chromatography coupled to mass spectrometry (TD-2D-GC-MS/FPD) and assessed whether the concentration of the volatiles benzene and 1,2-dichloroethane exceeded recommended exposure limits (REL). Products were taken from transport containers and analyzed for outgassing of volatiles. Furthermore, experimental outgassing was performed on packaging materials and textiles, to simulate the hazards tainting from globally shipped goods. The mean amounts of benzene in analyzed container air were 698-fold higher, and those of ethylene dichloride were 4.5-fold higher than the corresponding REL. More than 90% of all containers struck with toluene residues higher than its REL. For 1,2-dichloroethane 53% of containers, transporting shoes exceeded the REL. In standardized experimental fumigation of various products, outgassing of 1,2-dichloroethane under controlled laboratory conditions took up to several months. Globally produced transported products tainted with toxic industrial chemicals may contribute to the mixture of volatiles in indoor air as they are likely to emit for a long period. These results need to be taken into account for further evaluation of safety standards applying to workers and consumers.

Alternative drugs go global: possible lead and/ or mercury intoxication from imported natural health products and a need for scientifically evaluated poisoning monitoring from environmental exposures.

BACKGROUND: With increases in globalization, cultural remedies from Chinese, Ayurvedic, Arab and other traditions have become more available to international consumers, offering unfamiliar "Natural Health Products" (NHP), used as alternative medicine or supplementary medicine. Contamination with toxic ingredients including lead, mercury, arsenic, and other toxic elements has been documented in several of these products from various parts of the globe, particularly from some parts of Asia and the Orient. FINDINGS: We have been following this development in the last 6 years and have analyzed n = 20 such products (60 analyses) from patients with intoxication symptoms in a pilot study, showing alarming high concentrations of mercury and/or lead (the first one in "therapeutic" doses). 82 % of the studied NHP contained lead concentrations above the EU limit for dietary supplements. 62 % of the samples exceeded the limit values for mercury. Elevated blood lead and mercury levels in patients along with clinical intoxication symptoms corroborate the causal assumption of intoxication (s). We present one detailed clinical case report of severe lead and mercury intoxications and give an overview about blood concentration related symptoms and signs of n = 41 case reports of mercury intoxications of the German monitoring BfR-DocCenter. CONCLUSIONS: For NHP there is evidence on a distinct toxicological risk with alarming low awareness for a possible intoxication which prevents potentially life-saving diagnostic steps in affected cases. In many cases patients do not communicate the events to their physicians or the local health authority so that case reports (e.g. the BfR-DocCentre) are missing. Thus, there is an urgent need to raise awareness and to initiate more suitable monitory systems (e.g. National Monitoring of Poisonings) and control practice protecting the public.

Health risks in international container and bulk cargo transport due to volatile toxic compounds.

To ensure the preservation and quality of the goods, physical (i.e. radiation) or chemical pest control is needed. The dark side of such consents may bear health risks in international transport and production sharing. In fact, between 10% and 20% of all containers arriving European harbors were shown to contain volatile toxic substances above the exposure limit values. Possible exposure to these toxic chemicals may occur not only for the applicators but also the receiver by off gassing from products, packing materials or transport units like containers. A number of intoxications, some with lethal outcome, occur not only during the fumigation, but also during freight transport (on bulk carriers and other transport vessels), as well as in the logistic lines during loading and unloading. Risk occupations include dock-workers, seafarers, inspectors, as well as the usually uninformed workers of importing enterprises that unload the products. Bystanders as well as vulnerable consumers may also be at risk. Ongoing studies focus on the release of these toxic volatile substances from various goods. It was shown that the half-lives of the off-gassing process range between minutes and months, depending on the toxic substance, its chemical reactivity, concentration, the temperature, the contaminated matrix (goods and packing materials), and the packing density in the transport units. Regulations on declaration and handling dangerous goods are mostly not followed. It is obvious that this hazardous situation in freight transport urgently requires preventive steps. In order to improve awareness and relevant knowledge there is a need for more comprehensive information on chemical hazards and a broader implementation of the already existing regulations and guidelines, such as those from ILO, IMO, and national authorities. It is also necessary to have regular controls by the authorities on a worldwide scale, which should be followed by sanctions in case of disregarding regulations. Further, fumigated containers must have a warning sign corresponding to international recommendations and national regulations, and freight documents have to indicate any potential hazard during stripping the goods.

How conflicted authors undermine the World Health Organization (WHO) campaign to stop all use of asbestos: spotlight on studies showing that chrysotile is carcinogenic and facilitates other non-cancer asbestos-related diseases.

The silicate mineral asbestos is categorized into two main groups based on fiber structure: serpentine asbestos (chrysotile) and amphibole asbestos (crocidolite, amosite, anthophyllite, tremolite, and actinolite). Chrysotile is used in more than 2 000 applications and is especially prevalent in the construction industry. Although its use is banned or restricted in more than 52 countries, an estimated 107 000 workers die from asbestos exposure each year, and approximately 125 million workers continue to be exposed. Furthermore, ambient exposures persist to which the public is exposed, globally. Today, the primary controversies regarding the use of asbestos are the potencies of different types of asbestos, as opposed whether or not asbestos causes morbidity and mortality. The asbestos industry has promoted and funded research based on selected literature, ignoring both clinical and scientific knowledge. In this piece, we highlight a prominent example of a conflicted publication that sought to undermine the World Health Organization (WHO) campaign to stop the use of all forms of asbestos, including chrysotile asbestos. Independent and rigorous scientific data provide sufficient evidence that chrysotile asbestos, like other forms of asbestos, is a cause of asbestos-related morbidity and premature mortality.

Ethics, morality, and conflicting interests: how questionable professional integrity in some scientists supports global corporate influence in public health.

Clinical and public health research, education, and medical practice are vulnerable to influence by corporate interests driven by the for-profit motive. Developments over the last 10 years have shown that transparency and self-reporting of corporate ties do not always mitigate bias. In this article, we provide examples of how sound scientific reasoning and evidence-gathering are undermined through compromised scientific enquiry resulting in misleading science, decision-making, and policy intervention. Various medical disciplines provide reference literature essential for informing public, environmental, and occupational health policy. Published literature impacts clinical and laboratory methods, the validity of respective clinical guidelines, and the development and implementation of public health regulations. Said literature is also used in expert testimony related to resolving tort actions on work-related illnesses and environmental risks. We call for increased sensitivity, full transparency, and the implementation of effective ethical and professional praxis rules at all relevant regulatory levels to rout out inappropriate corporate influence in science. This is needed because influencing the integrity of scientists who engage in such activities cannot be depended upon.

Accidental exposure to gas emissions from transit goods treated for pest control.

BACKGROUND: International phytosanitary standards ISPM 15 require (since 2007) fumigation or heat treatment for shipping and storage. Those dealing with fumigated freight might be accidentally exposed. In this paper we report a series of three accidents of six storage room workers in a medium sized company regularly importing electronic production parts from abroad. METHODS: Patients (n=6, aged from 32-54 yrs.) and control group (n=30, mean 40 yrs.) donated blood and urine samples. The fumigants: ethylene oxide, methyl bromide, chloropicrin, ethylene dichloride, other halo-alkanes and solvents were analyzed by headspace gas chromatography/mass spectrometry (GCMS). For the quantitation of long term exposure/s, macromolecular reaction products (hemoglobin adducts) were used (with GCMS) as molecular dosimeter; additionally 8-OHdG and circulating mtDNA (cmtDNA) were analyzed as nonspecific biological effect markers. RESULTS: The hemoglobin adducts N-methyl valine (MEV) and N-(2-hydroxy ethyl) valine (HEV) were elevated after exposure to the alkylating chemicals methyl bromide and ethylene oxide. Under the consideration of known elimination kinetics and the individual smoking status (biomonitored with nicotine metabolite cotinine and tobacco specific hemoglobin adduct: N-(2 cyan ethyl) valines, CEV), the data allow theoretical extrapolation to the initial protein adduct concentrations at the time of the accident (the MEV/CEV levels were from 1,616 pmol/g globin to 1,880 pmol/g globin and HEV/CEV levels from 1,407 pmol/g globin to 5,049 pmol/g globin, and correlated with inhaled 0.4-1.5 ppm ethylene oxide. These integrated, extrapolated internal doses, calculated on the basis of biological exposure equivalents, confirmed the clinical diagnosis for three patients, showing severe intoxication symptoms. Both, cmtDNA and 8-OHdG, as non-specific biomarkers of toxic effects, were elevated in four patients. CONCLUSION: The cases reported here, stress the importance of a suitable risk assessment and control measures. We put emphasis on the necessity of human biomonitoring guidelines and the urgency for the relevant limit values.