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Background: Modern biomonitoring has expanded beyond its origins in occupational medicine to cover a wide variety of diagnostic procedures and assessments of environmental pollution, ranging from exposure to heavy metals and chemicals to the effects of pesticides and environmental tobacco smoke. In biomonitoring, the overall pollutant load and hazardous exposure of an organism is quantitatively determined, by monitoring the pollutants themselves, their metabolic products and/or conjugates with protein or DNA, in either serum, urine or other body fluids, as well as tissue samples in exceptional circumstances.Methods: A selective survey of the current literature is exemplified by our recent scientific and clinical experience.Results: Biomonitoring is an excellent way to monitor potentially hazardous substances, especially for the assessment of systemic uptake from chronic exposure and the evaluation of subsequent health risks. Investigative biomonitoring can highlight incidental/accidental intoxication in individuals and provide new categories of problematic pollutants relevant to the general population.Conclusions: In combination with diagnostic procedures, biomonitoring provides an important contribution to the rational assessment of currently recorded pollutants and resulting health risks. It is as an evaluation tool available in daily practice as well as in health and environmental research applications. Legislation is already implemented that incorporates biomonitoring within the remit of specified occupational health screening. [ABSTRACT FROM AUTHOR]

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., (© 2023. The Author(s).)

Recycling of electric and electronic waste products (e-waste) which amounted to more than 50 million metric tonnes per year worldwide is a massive and global operation. Unfortunately, an estimated 70-80% of this waste has not been properly managed because the waste went from developed to low-income countries to be dumped into landfills or informally recycled. Such recycling has been carried out either directly on landfill sites or in small, often family-run recycling shops without much regulations or oversights. The process traditionally involved manual dismantling, cleaning with hazardous solvents, burning and melting on open fires, etc., which would generate a variety of toxic substances and exposure/hazards to applicators, family members, proximate residents and the environment. The situation clearly calls for global responsibility to reduce the impact on human health and the environment, especially in developing countries where poor residents have been shouldering the hazardous burden. On the other hand, formal e-waste recycling has been mainly conducted in small scales in industrialized countries. Whether the latter process would impose less risk to populations and environment has not been determined yet. Therefore, the main objectives of this review are: 1. to address current trends and emerging threats of not only informal but also formal e-waste management practices, and 2. to propose adequate measures and interventions. A major recommendation is to conduct independent surveillance of compliance with e-waste trading and processing according to the Basel Ban Amendment. The recycling industry needs to be carefully evaluated by joint effort from international agencies, producing industries and other stakeholders to develop better processes. Subsequent transition to more sustainable and equitable e-waste management solutions should result in more effective use of natural resources, and in prevention of adverse effects on health and the environment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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 .

Background: The presence of pesticides in honey and related products is an increasing concern for consumers and producers, although there is lack of data on the current burden of exposure of the general human population through these products. We present a protocol for a systematic review and meta-analysis of contamination to insecticides, herbicides and fungicides of products from honeybees, and an estimation of how much the consumption of these products contributes to the ADI (Acceptable Daily Intake) of selected substances., Objectives: We aim to systematically review and meta-analyse studies on the contamination to plant protection products in honey, royal jelly, beeswax and propolis, applying the Navigation Guide and WHO-ILO systematic review methodology as an organizing framework., Data Sources: We will search electronic academic databases for potentially relevant records from PubMed, TOXNET and EMBASE. We will include quantitative studies analysing the contamination from insecticides, herbicides and fungicides in honey, propolis, royal jelly and beeswax. In particular, we will evaluate the presence of the following substances and classes of pesticides: Glyphosate, Chlorpyrifos, pyrethroid and neonicotinoid pesticides, fungicides and acaricides., Study Appraisal and Synthesis Methods: At least two authors will independently screen titles and abstracts at a first stage of review, and full texts at a second stage, of potentially eligible records against the eligibility criteria; data extraction of included studies will then be performed by at least two authors, in blind. At least two authors will assess risk of bias and the quality of evidence, using the most suited tools currently available. The data on prevalence of contaminated samples and concentration of pesticides in the products will be combined using meta-analysis: when more than three studies reporting the necessary measures to fit the models are available, meta-analysis will be performed separately by product and by exposure; otherwise, weighted descriptive analysis will be performed. We will report the results using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA)., Competing Interests: Declaration of competing interest All authors declare no financial conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (© 2019 The Authors Allergy Published by John Wiley & Sons Ltd.)

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., Competing Interests: Competing interests: The authors declare that they have no conflict of interest. HL conducted this study as part of the requirements for the German medical doctor degree at Charité—Universitätsmedizin Berlin, Berlin, Germany., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Cases of intoxications to gas from container's atmosphere have been described. For diagnosis, Fum Ex 2 questionnaire has been developed by the European Society for Environmental and Occupational Medicine. The aim of this study was to enhance knowledge on health effects of toxic substances in containers and to validate this questionnaire in medical follow-up and diagnosis., Materials and Methods: In 2014, 125 French dockers answered the questionnaire in a face-to-face interview., Results: 83.5% declared no exposure to fumigants or pesticides. Most frequently declared symptoms were fatigue and neurological disorders for dockers and respiratory irritation for refrigeration technicians. Only 28 workers wore regularly individual protection equipment., Conclusions: A "healthy worker" effect could explain low level of symptoms. Fum Ex 2 questionnaire is relevant for diagnosis. Workers in all steps of the logistic transport chain and consumers are exposed to containers' atmosphere.

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., Competing Interests: Not applicableConsent for the replication of figures previously published in other publications exists (the authors own the copyright).The authors report no conflicts of interest in this work. Disclosure: The manuscript presents the views of the authors and not necessarily the opinions of organizations they represent. DJ and EP are staff members of the World Health Organization (WHO) Regional Office for Europe. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decision or stated policy of the World Health Organization.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Fumigation of transport containers is common practice to protect stored products from pests. Yet little is known about the desorption times and effects of the highly toxic gases used in this process. To shed light on the behavior of fumigants in real food, we treated sunflower seeds (Helianthus annuus L.) with 100ppm phosphine (PH 3 ), methyl bromide (MeBr) or 1,2-dichloroethane (DCE) for 72h. The compound concentrations in the air were then analyzed by thermal desorption/2D gas chromatography coupled to mass spectrometry and flame photometric detection (TD-2D-GC-MS/FPD). A desorption time of several months was observed for DCE, whereas PH 3 and MeBr were outgassed in a matter of days. To investigate possible interactions between gases and constituents of the seeds, non-fumigated, fumigated and outgassed samples were analyzed by headspace solid-phase microextraction GC-MS. We observed significantly different volatile profiles in fumigated and subsequently outgassed seeds compared to non-fumigated seeds. Whereas PH 3 -treated seeds released far more terpenoids, the volatile pattern of seeds exposed to DCE revealed significantly fewer terpenoids but more aldehydes. These changes are likely to affect food aroma characteristics., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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.

Objectives: The use of genetically engineered enzymes in the synthesis of flavourings, fragrances and other applications has increased tremendously. There is, however, a paucity of data on sensitisation and/or allergy to the finished products. We aimed to review the use of genetically modified enzymes and the enormous challenges in human biomonitoring studies with suitable assays of specific IgE to a variety of modified enzyme proteins in occupational settings and measure specific IgE to modified enzymes in exposed workers., Methods: Specific IgE antibodies against workplace-specific individual enzymes were measured by the specific fluorescence enzyme-labelled immunoassay in 813 exposed workers seen in cross-sectional surveys., Results: Twenty-three per cent of all exposed workers showed type I sensitisation with IgE antibodies directed against respective workplace-specific enzymes. The highest sensitisation frequencies observed were for workers exposed enzymes derived from α-amylase (44%), followed by stainzyme (41%), pancreatinin (35%), savinase (31%), papain (31%), ovozyme (28%), phytase (16%), trypsin (15%) and lipase (4%). The highest individual antibody levels (up to 110 kU/L) were detected in workers exposed to phytase, xylanase and glucanase. In a subgroup comprising 134 workers, detailed clinical diagnostics confirmed work-related symptoms. There was a strong correlation (r=0.75, p<0.0001) between the symptoms and antibody levels. Workers with work-related respiratory symptoms showed a higher prevalence for the presence of specific IgE antibodies against workplace-specific enzymes than asymptomatic exposed workers (likelihood ratio 2.32, sensitivity 0.92, specificity 0.6)., Conclusions: Our data confirm the previous findings showing that genetically engineered enzymes are potent allergens eliciting immediate-type sensitisation. Owing to lack of commercial diagnostic tests, few of those exposed receive regular surveillance including biomonitoring with relevant specific IgE assays., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Isocyanates are a well-known and frequent cause of occupational asthma. The implementation of specific inhalation challenges (SICs) is the gold standard in asthma diagnosis supporting occupational case history, lung function testing, specific skin prick tests and the detection of specific IgE. However, the diagnosis is not always definitive. An interesting new approach, analyses of individual genetic susceptibilities, requires discrimination between a positive SIC reaction arising from IgE-mediated immune responses and one from other pathophysiological mechanisms. Hence, additional refinement tools would be helpful in defining sub-classes of occupational asthma and diagnosis. We used total IgE levels, specific IgE and SIC results for sub-classification of 27 symptomatic isocyanate workers studied. Some mutations in glutathione S-transferases (GSTs) are suspected either to enhance or to decrease the individual risk in the development of isocyanate asthma. Our patient groups were assessed for the point mutations GSTP1*I105V and GSTP1*A114V as well as deletions (null mutations) of GSTM1 and GSTT1. There seems to be a higher risk in developing IgE-mediated reactions when GSTM1 is deleted, while GSTT1 deletions were found more frequently in the SIC positive group. Blood samples taken before SIC, 30-60 min and 24h after SIC, were analyzed for histamine and IL-4, classical markers for the IgE-mediated antigen-specific activation of basophils or mast cells. We suggest that the utility of histamine measurements might provide an additional useful marker reflecting isocyanate-induced cellular reactions (although the sampling times require optimization). The promising measurement of IL-4 is not feasible at present due to the lack of a reliable, validated assay., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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.

Repeated inhalative exposures to antigenic material from a variety of sources, mainly from moulds, thermophilic Actinomycetes, and avians, respectively, can induce immune responses with the clinical picture of extrinsic allergic alveolitis (EAA) or hypersensitivity pneumonitis. Delays of years or even decades till the diagnosis is made are not uncommon; frequent misdiagnoses include allergic asthma, COPD, recurrent flue and other infections. We provide here the state of the art references, a detailed case description and recommend a current diagnostics schema.

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.

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.

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.

Objectives: After cargo with PCB-containing transformer oil waste was damaged in heavy seas, the vessel crew exposed to PCB developed itching and acne-form eruption of the skin. The objective of our study was to analyse this work-related incident and its effects on health., Methods: Air and wipe test samples were taken in the ship for analysis of PCB (28/52/101/138/153/180); clinical investigations of all seafarers (n = 6) included lung function, chest X-ray, clinical chemistry and biomonitoring (plasma PCBs, chlorophenols in urine) measured after a latency of 7 weeks. The biomonitoring data were adjusted according to age-related reference values and validated against controls (n = 96)., Results: Biomonitoring showed elevated PCB-28-/52/-102/-138 congeners (mean 1.16/0.91/136, ∑PCB: 5.82 μg/l), which correlates with the dust samples from the cargo hold (∑PCB. 9,440 mg/m(2)) and with 6.1 and 5.0 μg/m(3) in stern and bow cargo air samples. IgE elevation in two seafarers and substantial blood sedimentation rate increase with anaemia or pulmonary emphysema were unlikely to be caused by PCB exposure. Although two members showed slightly elevated airway resistance values, other lung function parameters were normal and reactive airways dysfunction syndrome due to PCBs could be excluded. Elevated chlorophenols in urine could contribute to the manifestation of chloracne., Conclusions: PCB-52/-101/-138 found in plasma and in air samples confirm exposure to PCB. Acne-form skin eruptions were from occupational exposure to polychlorinated biphenyls in the spilt transformer oil. There were no other abnormal findings in medical and clinical examinations that could be attributed to PCBs. This does not exclude possible long-term effects.

There is a need for a panel of suitable biomarkers for detection of environmental chemical exposure leading to the initiation or progression of degenerative diseases or potentially, to cancer. As the peripheral blood may contain increased levels of circulating cell-free DNA in diseased individuals, we aimed to evaluate this DNA as effect biomarker recognizing vulnerability after exposure to environmental chemicals. We recruited 164 individuals presumably exposed to halo-alkane-based pesticides. Exposure evaluation was based on human biomonitoring analysis; as biomarker of exposure parent halo-methanes, -ethanes and their metabolites, as well as the hemoglobin-adducts methyl valine and hydroxyl ethyl valine in blood were used, complemented by expert evaluation of exposure and clinical intoxication symptoms as well as a questionnaire. Assessment showed exposures to halo alkanes in the concentration range being higher than non-cancer reference doses (RfD) but (mostly) lower than the occupational exposure limits. We quantified circulating DNA in serum from 86 individuals with confirmed exposure to off-gassing halo-alkane pesticides (in storage facilities or in home environment) and 30 non-exposed controls, and found that exposure was significantly associated with elevated serum levels of circulating mitochondrial DNA (in size of 79 bp, mtDNA-79, p = 0.0001). The decreased integrity of mtDNA (mtDNA-230/mtDNA-79) in exposed individuals implicates apoptotic processes (p = 0.015). The relative amounts of mtDNA-79 in serum were positively associated with the lag-time after intoxication to these chemicals (r = 0.99, p<0.0001). Several months of post-exposure the specificity of this biomarker increased from 30% to 97% in patients with intoxication symptoms. Our findings indicate that mitochondrial DNA has a potential to serve as a biomarker recognizing vulnerable risk groups after exposure to toxic/carcinogenic chemicals.

Purpose: Early recognition improves the prognosis of isocyanate asthma. A major unanswered question is whether IgE-dependent mechanisms are of diagnostic value? Our objective was to appraise serological methods using various methylenediphenyl diisocyanate (MDI)-albumin conjugates and weigh up the data versus the outcome of standardized comprehensive clinical diagnostics to evaluate the viability of immunological analysis in supportive MDI-asthma diagnosis (OAI)., Methods: Specific IgE (sIgE) and IgG (sIgG) binding was measured with fluorescence enzyme immunoassay in 43 study subjects (using conjugates prepared in-vapor, in-solution and commercial preparations). The differential clinical diagnosis included standardized measurement of pulmonary function, non-specific bronchial hyper-responsiveness, specific MDI-prick test (MDI-SPT) and specific inhalation challenge (MDI-SIC)., Results: Detailed diagnostic scheme allows the differential OAI and MDI-induced hypersensitivity pneumonitis (PI). The presumed OAI diagnoses were confirmed in 84 % (45 % cases having demonstrable sIgE antibodies) with RR 5.7, P > 0.001, when OAI diagnosis is correlated with MDI-SIC/MDI-SPT (RR 1.28 for MDI-SIC alone); sIgG antibodies were clinically relevant for PI and not for the OA diagnosis. MDI-specific IgE data generated with commercial ImmunoCAP preparations show high correlation with our in-vapor generated MDI conjugates., Conclusions: Isocyanate-specific IgE antibodies are not always detectable but their presence is strongly predictive of OAI and supportive for the diagnosis. MDI-SPT can be a valuable parameter differentiating OAI and PI. We have confirmed and extended published data showing that isocyanate-albumin conjugates perform better in specific antibody assays when prepared with volatile phase formulations and would like to stress additionally the necessity for further refinements and standardization in clinical diagnostics procedures.

Background: Airborne enzymes behave as potent respiratory allergens. Till date, allergic disorders caused by genetically engineered enzymes widely used in the industry, have not been reported., Results and Conclusions: We describe a worker employed in the detergent industry who developed asthma and rhinitis from IgE-mediated sensitization to the thermostable endo-alpha-amylase Termamyl® and to the protease Savinase®. This is the first report showing that Termamyl® elicits allergic respiratory disorders in humans., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Although ozone-depleting methyl bromide was destined for phase-out by 2005, it is still widely applied as a consequence of various critical-use-exemptions and mandatory international regulations aiming to restrict the spread of pests and alien species (e.g. in globalized transport and storage). The withdrawal of methyl bromide because of its environmental risk could fortuitously help in the containment of its human toxicity., Methods: We performed a systematic review of the literature, including in vitro toxicological and epidemiological studies of occupational and community exposure to the halogenated hydrocarbon pesticide methyl bromide. We focused on toxic (especially chronic) or carcinogenic effects from the use of methyl bromide, on biomonitoring data and reference values. Eligible epidemiological studies were subjected to meta-analysis., Results: Out of the 542 peer reviewed publications between 1990-2011, we found only 91 referring to toxicity of methyl bromide and 29 using the term "carcinogenic", "neoplastic" or "mutagenic". Several studies provide new additional data pertaining to the mechanistic aspects of methyl bromide toxicity. Few studies have performed a detailed exposure assessment including biomonitoring. Three evaluated epidemiological studies assessed a possible association between cancer and methyl bromide. Overall, exposure to methyl bromide is associated with an increased risk of prostate cancer OR, 1.21; 95% CI (0,98-1.49), P = 0.076. Two epidemiological studies have analyzed environmental, non-occupational exposure to methyl bromide providing evidence for its health risk to the general public. None of the epidemiological studies addressed its use as a fumigant in freight containers, although recent field and case reports do refer to its toxic effects associated with its use in shipping and storage., Conclusions: Both the epidemiological evidence and toxicological data suggest a possible link between methyl bromide exposure and serious health problems, including prostate cancer risk from occupational and community exposure. The environmental risks of methyl bromide are not in doubt, but also its health risks, especially for genetically predisposed subjects, should not be underestimated.

Headache, concentration and memory disorders, dizziness and nausea, skin irritation, respiratory distress, and muscle cramps - isolated or in various combinations - may be the result of acute or chronic intoxication by fumigants. The occurrence of these symptoms in workers who are engaged in the opening and unloading of containers, unpacking of imported goods, ventilating of containers, or working on bulk carriers are urgent indications of intoxication by fumigants or other toxic chemical residues in the transported goods. The severity of the disorder depends on the concentration and duration of exposure, distribution and release of the fumigant, its kinetics, the individual susceptibility of the person, as well as any simultaneous exposure to other toxic substances. Physical symptoms, acute and chronic health effects due to contact with fumigants, are complex and difficult to discover. In this article we explain how to identify the guiding symptoms and describe the appropriate diagnostic steps and the prevention of such events on cargo vessels as well as in the logistics and the handling of imported goods.

The fumigation of freight containers to protect transported goods from fungal and pest infestation has increased worldwide in the last five years due to international regulations requiring fumigation or heat treatment of wooden packaging material and dunnage. We have found in 2008 that every sixth container and its contents do retain harmful concentrations of various fumigants and chemicals, representing a significant health risk for port and transport workers, customs officials, warehousemen, store employees and consumers. The shipping documents of these containers did not provide any information about the fumigation procedure or the used fumigant. We report here the cases of 26 patients introduced to our outpatient clinic with presumed intoxication to fumigants, or with symptoms due to inhaling the air out of fumigated containers. All patients were examined from 2007 to 2010 according to a standardized comprehensive diagnostic program. We were able to confirm the diagnosis based on typical symptoms and extensive clinical examination; by laboratory analysis we identified ethylene dichloride, methyl bromide, phosphine and methylene chloride. The predominant symptoms were headaches, concentration and memory problems, dizziness and nausea, irritation of the skin and mucous membranes and a reduced ability to do exercise. In addition to the neurological and neuropsychological impairments our analyses verified the development of reactive airways dysfunction syndrome (RADS) in 14 of 26 patients with long lasting symptoms due to their contact with fumigants. Intoxications with fumigants are serious and could be avoided. These systematical explored cases show the sustainable impact for health and socio-economic wellbeing. These findings also emphasize the necessity for international standards on permitted fumigants, appropriate labeling in the shipping documents and handling of fumigated containers., (Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.)

Background: Isocyanates are some of the leading occupational causes of respiratory disorders, predominantly asthma. Adequate exposure monitoring may recognize risk factors and help to prevent the onset or aggravation of these aliments. Though, the biomonitoring appears to be most suitable for exposure assessment, the sampling time is critical, however. In order to settle the optimal time point for the sample collection in a practical biomonitoring approach, we aimed to measure the elimination of isocyanate urine metabolites., Methods: A simple biomonitoring method enabling detection of all major diamine metabolites, from mono-, poly- and diisocyanates in one analytical step, has been established. Urine samples from 121 patients undergoing inhalative challenge tests with diisocyanates for diagnostic reasons were separated by gas chromatography and analyzed with mass spectrometry (GC-MS) at various time points (0-24 h) after the onset of exposure., Results: After controlled exposures to different concentrations of diisocyanates (496 ± 102 ppb-min or 1560 ± 420 ppb-min) the elimination kinetics (of respective isocyanate diamine metabolites) revealed differences between aliphatic and aromatic isocyanates (the latter exhibiting a slower elimination) and a dose-response relationship. No significant differences were observed, however, when the elimination time patterns for individual isocyanates were compared, in respect of either low or high exposure or in relation to the presence or absence of prior immunological sensitization., Conclusions: The detection of isocyanate metabolites in hydrolyzed urine with the help of gas chromatography combined with mass spectrometric detection system appears to be the most suitable, reliable and sensitive method to monitor possible isocyanate uptake by an individual. Additionally, the information on elimination kinetic patterns must be factored into estimates of isocyanate uptake before it is possible for biomonitoring to provide realistic assessments of isocyanate exposure. The pathophysiological elimination of 1,6-hexamethylene diamine, 2,4-diamine toluene, 2,6-diamine toluene, 1,5-naphthalene diamine, 4,4'-diphenylmethane diamine and isophorone diamines (as respective metabolites of: 1,6-hexamethylene diisocyanate, 2,4-toluene diisocyanate and 2,6 toluene diisocyanate, 1,5-naphthalene diisocyanate, 4,4'-diphenylmethane diisocyanate and isophorone diisocyanates) differs between individual isocyanates' diamines.

Fumigants and volatile industrial chemicals are particularly hazardous to health when a freight container is fumigated or the contaminated material is introduced into its enclosed environment. Phosphine is now increasingly used as a fumigant, after bromomethane--the former fumigant of choice--has been banned by the Montreal Protocol. We have enhanced our previously established thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) method by integrating a second gas chromatographic dimension and a flame photometric detector to allow the simultaneous detection of phosphine and volatile organic compounds (VOCs), providing a novel application. A thermal desorption system is coupled to a two dimensional gas chromatograph using both mass spectrometric and flame photometric detection (TD-2D-GC-MS/FPD). Additionally, the collection of mass spectrometric SIM and Scan data has been synchronised, so only a single analysis is now sufficient for qualitative scanning of the whole sample and for sensitive quantification. Though detection limits for the herewith described method are slightly higher than in the previous method, they are in the low μL m(-3) range, which is not only below the respective occupational exposure and intervention limits but also allows the detection of residual contamination after ventilation. The method was developed for the separation and identification of 44 volatile substances. For 12 of these compounds (bromomethane, iodomethane, dichloromethane, 1,2-dichlorethane, benzene, tetrachloromethane, 1,2-dichloropropane, toluene, trichloronitromethane, ethyl benzene, phosphine, carbon disulfide) the method was validated as we chose the target compounds due to their relevance in freight container handling., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Protection against infestation of a container cargo by alien species is achieved by mandatory fumigation with pesticides. Most of the effective fumigants are methyl and ethyl halide gases that are highly toxic and are a risk to both human health and the environment. There is a worldwide need for a reliable and robust analytical screening procedure for these volatile chemicals in a multitude of health and environmental scenarios. We have established a highly sensitive broad spectrum mass spectrometry method combined with thermal desorption gas chromatography to detect, identify and quantify volatile pesticide residues. Using this method, 1201 random ambient air samples taken from freight containers arriving at the biggest European ports of Hamburg and Rotterdam were analyzed over a period of two and a half years. This analytical procedure is a valuable strategy to measure air pollution from these hazardous chemicals, to help in the identification of pesticides in the new mixtures/formulations that are being adopted globally and to analyze expired breath samples after suspected intoxication in biomonitoring.

Residues of pesticide fumigants and toxic industrial chemicals in freight containers represent a health hazard to employees and consumers, especially since freight containers are sealed for transport and distributed widely throughout the importing countries before being opened for unloading. We investigated 2113 freight containers arriving at the second largest container terminal in Europe, Hamburg, Germany, over a 10-week period in 2006. The countries of origin, type of contents and the pesticide fumigation history declared on labels attached to the container were recorded. We determined that 1478 (70%) containers were contaminated with toxic chemicals above chronic reference exposure levels; 761 (36%) even exceeded the higher acute reference exposure level thresholds. Benzene and/or formaldehyde contamination was 4-times greater than for fumigants. Our findings indicate a health risk for dockworkers, container unloaders and even end-consumers, especially as many of the cancerogenic or toxic gases elude subjective detection.

The increasing transport of goods worldwide is mainly carried in standard containers. These containers are frequently fumigated in order to protect freight from pests and to follow regulations of importing countries. Fumigants as well as toxic industrial chemicals can adsorb to goods and be emitted from them over various periods of time. This review is based on a literature search, analyses of air samples from a randomized selection of import containers at the port of Hamburg and clinical investigations of intoxicated subject. These data indicate that about 70% of imported containers exceed national or international threshold levels, about one sixth exceeding occupational exposure limits of fumigants and/or toxic industrial chemical, 0.5% had concentrations immediately dangerous to life or health. Intoxications by inhalation mainly occur in workers in the logistics area. No information exists on possible fumigation in small and medium-sized companies where the container units are unloaded. Neurological and respiratory ailments dominated in patients from our outpatient clinic and those reported in the literature: symptoms were often misdiagnosed. Our results confirm findings of other investigators that subjects who unload containers or have otherwise intensive contact with imported goods are frequently exposed to toxic or very toxic volatile chemicals. It can be assumed that there are many unrecognized cases and also health risks to the ultimate consumers of transported goods. History taking targeted on potential exposure is of great diagnostic importance in elucidating typical temporal relationship between exposure by inhalation and symptoms such as headache, skin irritation, cough, dyspnea, diarrhoea and neurological deficits. Detailed investigations by medical specialists is necessary to confirm suspected diagnoses. This should be combined with immediate special analyses of air samples and laboratory tests (biological monitoring)., (Georg Thieme Verlag KG Stuttgart, New York.)

Background: Risks from electromagnetic devices are of considerable concern. Electrohypersensitive (EHS) persons attribute a variety of rather unspecific symptoms to the exposure to electromagnetic fields. The pathophysiology of EHS is unknown and therapy remains a challenge., Objectives: Heavy metal load has been discussed as a potential factor in the symptomatology of EHS patients. The main objective of the study was to test the hypothesis of a link between EHS and heavy metal exposure., Methods: We measured lead, mercury and cadmium concentrations in the blood of 132 patients (n=42 males and n=90 females) and 101 controls (n=34 males and n=67 females)., Results: Our results show that heavy metal load is of no concern in most cases of EHS but might play a role in exceptional cases., Conclusions: The data do not support the general advice to heavy metal detoxification in EHS., (Copyright 2009 Elsevier B.V. All rights reserved.)

During recent decades the industrial use of isocyanates has expanded enormously due to the huge product palette with a variety of different properties. As opposed to the fast technical development, there is a delay in the formulation of respective occupational health and safety regulations. Adverse health effects of isocyanates are mainly due to inhalative exposure. In addition, cutaneous contact causes toxic as well as allergic reactions. Oligomeric and polymeric isocyanates that are mostly used in the industry are only regulated in the Technical Rules for Hazardous Substances 430 (TRGS 430), but not by the mandatory occupational medical surveillance directive (Arbeitsmedizinische Vorsorgeverordnung). Although the TRGS 430 facilitates risk assessment (e. g., the aerosol penetration factor is related to the size of aerosols; only the acute irritative effect of oligomeric and polymeric isocyanates as shown in animal studies is taken into consideration in the case of defining a so-called evaluation factor), so far this new regulation has not yet been implemented in practice according to our own findings.

The cardiac hormone atrial natriuretic peptide (ANP) signals via interaction with a plasma membrane receptor, which has guanylyl cyclase (GC) activity and is referred to as GC-A. Desensitization of GC-A is thought to represent a physiologically important regulatory mechanism, but the signaling pathways implicated and cell type-specific effects are still poorly understood. Here we demonstrate that sustained exposure to either ANP itself or the bioactive lipid lysophosphatidic acid (LPA) elicits GC-A desensitization in MA-10 Leydig cells. Both reactions show similar kinetics and evoke equal decreases (by 40%) in GC-A hormone responsiveness. Homologous (ANP induced) desensitization, in which cGMP is generated as second messenger, is blocked by distinct cAMP-dependent protein kinase [protein kinase A (PKA)] inhibitors, H 89, and Rp-8-CPT-cAMPs, providing evidence that PKA mediates the reaction. Accordingly, the ANP/cGMP-elicited effects are mimicked by a cAMP analog, 8-bromo-cAMP. The LPA-induced (heterologous) desensitization is not blocked by PKA inhibition, indicating a different signaling pathway. LPA, but not ANP, enhances ERK phosphorylation and induces cell rounding together with a dramatic reorganization of actin filaments. Consistent with the identification of LPA receptor (LPA2 and LPA3) gene expression, the findings are indicative of LPA receptor-mediated reactions. This study demonstrates for the first time coexistence of homologous and heterologous desensitization of GC-A in the same cell type, reveals that these reactions are mediated by different pathways, and identifies a novel cross talk between phospholipid and natriuretic peptide signaling. The morphoregulatory activities exerted by LPA suggest a crucial role for Leydig cell physiology.