Respiratory Irritation Research Articles

Nebulized heparin for burned patients with inhalation injury: a review

The presence of inhalation injury has a negative impact on the evolution of burned patients, being associated with increased mortality. It occurs as a direct consequence of thermal action, or secondary to the presence of respiratory irritants or absorption of toxins, and actual therapeutic management is mainly supportive. Several clinical findings are relevant to raising suspicion and guiding further examinations, fiberoptic bronchoscopy being the gold standard of diagnosis and staging. In burned patients with inhalation injuries, various reports showed that nebulized heparin (5,000 or 10,000 units) with a 4-hour administration regimen leads to improved outcome, reduces the days of mechanical ventilation and consequently the length of hospital stay, reduces pulmonary complications and improves lung function, having a safe profile, with fewer side effects.

Relationships between blooms of Karenia brevis and hypoxia across the West Florida Shelf

Harmful algal blooms (HABs) caused by the dinoflagellate Karenia brevis on the West Florida Shelf have become a nearly annual occurrence causing widespread ecological and economic harm. Effects range from minor respiratory irritation and localized fish kills to large-scale and long-term events causing massive mortalities to marine organisms. Reports of hypoxia on the shelf have been infrequent; however, there have been some indications that some HABs have been associated with localized hypoxia. We examined oceanographic data from 2004 to 2019 across the West Florida Shelf to determine the frequency of hypoxia and to assess its association with known HABs. Hypoxia was present in 5 of the 16 years examined and was always found shoreward of the 50-meter bathymetry line. There were 2 clusters of recurrent hypoxia: midshelf off the Big Bend coast and near the southwest Florida coast. We identified 3 hypoxic events that were characterized by multiple conductivity, temperature, and depth (CTD) casts and occurred concurrently with extreme HABs in 2005, 2014, and 2018. These HAB-hypoxia events occurred when K. brevis blooms initiated in early summer months and persisted into the fall likely driven by increased biological oxygen demand from decaying algal biomass and reduced water column ventilation due to stratification. There were also four years, 2011, 2013, 2015, and 2017, with low dissolved oxygen located near the shelf break that were likely associated with upwelling of deeper Gulf of Mexico water onto the shelf. We had difficulty in assessing the spatiotemporal extent of these events due to limited data availability and potentially unobserved hypoxia due to the inconsistent difference between the bottom of the CTD cast and the seafloor. While we cannot unequivocally explain the association between extreme HABs and hypoxia on the West Florida Shelf, there is sufficient evidence to suggest a causal linkage between them.

Strategies to Improve Drug Strength in Nasal Preparations for Brain Delivery of Low Aqueous Solubility Drugs.

Intranasal administration is a promising route for brain drug delivery. However, it can be difficult to formulate drugs that have low water solubility into high strength intranasal solutions. Hence, the purpose of this work was to review the strategies that have been used to increase drug strength in intranasal liquid formulations. Three main groups of strategies are: the use of solubilizers (change in pH, complexation and the use cosolvents/surfactants); incorporation of the drugs into a carrier nanosystem; modifications of the molecules themselves (use of salts or hydrophilic prodrugs). The use of high amounts of cosolvents and/or surfactants and pH decrease below 4 usually lead to local adverse effects, such as nasal and upper respiratory tract irritation. Cyclodextrins and (many) different carrier nanosystems, on the other hand, could be safer for intranasal administration at reasonably high concentrations, depending on selected excipients and their dose. While added attributes such as enhanced permeation, sustained delivery, or increased direct brain transport could be achieved, a great effort of optimization will be required. On the other hand, hydrophilic prodrugs, whether co-administered with a converting enzyme or not, can be used at very high concentrations, and have resulted in a fast prodrug to parent drug conversion and led to high brain drug levels. Nevertheless, the choice of which strategy to use will always depend on the characteristics of the drug and must be a case-by-case approach.

Many oil wells, one evil: comprehensive assessment of toxic metals concentration, seasonal variation and human health risk in drinking water quality in areas surrounding crude oil exploration facilities in rivers state, Nigeria

Background: Oil and natural gas extraction have produced environmental pollution at levels that affect reproductive health of indigenous populations. Accordingly, polluted drinking water from physical, chemical and heavy metals can result in serious health problems, like anemia, kidney failure, immunosuppression, neurological impairments, gastrointestinal as well as respiratory irritation, skeletal system abnormalities, liver inflammation, liver cancer, cardiovascular diseases after chronic exposure and other cancer diseases with negative health effects. These diseases types remain associated to high amounts of heavy metal elements such as lead, chromium, zinc, copper, cadmium, manganese as well as nickel etc. Objectives: Compare differences in water quality parameters in the study area (determine the level of pollutions in the different sites). Methodology: The investigation made use of standard analytical methodologies. All sampling, conservation, transportation as well as analysis followed the usual APHA procedures (2012). To prevent degradation of the organic substances, all obtained samples were transferred to the laboratory, while keeping in an icebox. Results: Result shows that during wet season, the mean values obtained for water quality parameters were significantly lower in site 9 compared with that obtained in other sites (p<0.05) with the exemptions of temperature, DO, BOD, COD, acidity, TH, TDS, K, Mg, Zn, Mn, Cd, Pb, Cu, Cr, NH3, NO2, NO3, Ni though slightly lower in most cases in site 9 were not significantly different (p>0.05) and both alkalinity and SO4 which were significantly higher in site 9 than site 1 (p<0.05). Result obtained during dry season reveals that there is no remarkable difference in pH, acidity, Pb and Ni between the nine sites (p>0.05) while other water quality parameters were significantly lower in site 9 than other sites excluding Cl and Mg which were both significantly higher in site 9 than site 8 (p<0.05). Conclusion: To guarantee quality groundwater supply for various purposes in Nigeria's core Niger Delta region, extra efforts must be taken to fully understand hydrogeochemical features and its suitability. Thus, this study will aid in the development of a quantitative understanding of the effects of diverse causes on groundwater level fluctuations in any aquifer around the world. Also, this analysis reinforces a valuable resource for researchers, activists and public officials seeking to help enhance community awareness, planning and performance. The verdicts would remain a valuable guideline for policymakers, the Ministry of Water Resources and development practitioners, as this highlights the requirement for suitable approaches toward mitigating toxic element of water resources contamination in the core Niger Delta toward safeguarding health of the public from carcinogenic as well as non-carcinogenic risks.

Evaluation of animal toxicity studies with diisocyanates regarding presence of thresholds for induction and elicitation of respiratory allergy by quantitative weight of evidence.

Animal toxicity studies on diisocyanates were evaluated using quantitative weight of evidence (QWoE) to test the hypothesis that the dose-response curve shows a threshold for the induction and/or elicitation of respiratory sensitization. A literature search identified 59 references that included at least two concentration groups of the diisocyanate and a vehicle-exposed concurrent control in the study design. These studies were subjected to a QWoE-assessment applying scoring criteria for quality and relevance/strength of effects relevant to the selected endpoint of respiratory sensitization. Overall, the studies assessing dose/concentration-response for diisocyanates with the endpoint, respiratory sensitization, were heterogenous regarding study design, animal models used, endpoints assessed, and quality. Only a limited number of the studies subjected to the QWoE-assessment allowed drawing conclusions about possible thresholds for respiratory sensitization. Highest quality and relevance/strength of effects scores were obtained by a series of studies specifically designed to investigate a potential threshold for elicitation of respiratory sensitization in the Brown Norway (BN) rat. These studies applied an elaborate study design to optimize induction of respiratory sensitization and reduce interference by respiratory tract irritation. In summary, the available studies provided moderate to good support for the existence of a threshold for elicitation and limited to moderate support for a threshold regarding induction of respiratory allergy by diisocyanates in experimental animals. However, a quantitative extrapolation of threshold values established in rodents to humans remains complex.

Chemical Emissions From Heated Vitamin E Acetate-Insights to Respiratory Risks From Electronic Cigarette Liquid Oil Diluents Used in the Aerosolization of Δ9-THC-Containing Products.

As of February 18, 2020, the e-cigarette, or vaping, product use associated lung injury (EVALI) outbreak caused the hospitalization of a total of 2,807 patients and claimed 68 lives in the United States. Though investigations have reported a strong association with vitamin E acetate (VEA), evidence from reported EVALI cases is not sufficient to rule out the contribution of other chemicals of concern, including chemicals in either THC or non-THC products. This study characterized chemicals evolved when diluent oils were heated to temperatures that mimic e-cigarette, or vaping, products (EVPs) to investigate production of potentially toxic chemicals that might have caused lung injury. VEA, vitamin E, coconut, and medium chain triglyceride (MCT) oil were each diluted with ethanol and then tested for constituents and impurities using a gas chromatograph mass spectrometer (GC/MS). Undiluted oils were heated at 25°C (control), 150°C, and 250°C in an inert chamber to mimic a range of temperatures indicative of aerosolization from EVPs. Volatilized chemicals were collected using thermal desorption tubes, analyzed using a GC/MS, and identified. Presence of identified chemicals was confirmed using retention time and ion spectra matching with analytic standards. Direct analysis of oils, as received, revealed that VEA and vitamin E were the main constituents of their oils, and coconut and MCT oils were nearly identical having two main constituents: glycerol tricaprylate and 2-(decanoyloxy) propane-1,3-diyl dioctanoate. More chemicals were measured and with greater intensities when diluent oils were heated at 250°C compared to 150°C and 25°C. Vitamin E and coconut/MCT oils produced different chemical emissions. The presence of some identified chemicals is of potential health consequence because many are known respiratory irritants and acute respiratory toxins. Exposure to a mixture of hazardous chemicals may be relevant to the development or exacerbation of EVALI, especially when in concert with physical damage caused by lung deposition of aerosols produced by aerosolizing diluent oils.

Quantifying Karenia brevis bloom severity and respiratory irritation impact along the shoreline of Southwest Florida.

Nearly all annual blooms of the toxic dinoflagellate Karenia brevis (K. brevis) pose a serious threat to coastal Southwest Florida. These blooms discolor water, kill fish and marine mammals, contaminate shellfish, cause mild to severe respiratory irritation, and discourage tourism and recreational activities, leading to significant health and economic impacts in affected communities. Despite these issues, we still lack standard measures suitable for assessing bloom severity or for evaluating the efficacy of modeling efforts simulating bloom initiation and intensity. In this study, historical cell count observations along the southwest Florida shoreline from 1953 to 2019 were used to develop monthly and annual bloom severity indices (BSI). Similarly, respiratory irritation observations routinely reported in Sarasota and Manatee Counties from 2006 to 2019 were used to construct a respiratory irritation index (RI). Both BSI and RI consider spatial extent and temporal evolution of the bloom, and can be updated routinely and used as objective criteria to aid future socioeconomic and scientific studies of K. brevis. These indices can also be used to help managers and decision makers both evaluate the risks along the coast during events and design systems to better respond to and mitigate bloom impacts. Before 1995, sampling was done largely in response to reports of discolored water, fish kills, or respiratory irritation. During this timeframe, lack of sampling during the fall, when blooms typically occur, generally coincided with periods of more frequent-than-usual offshore winds. Consequently, some blooms may have been undetected or under-sampled. As a result, the BSIs before 1995 were likely underestimated and cannot be viewed as accurately as those after 1995. Anomalies in the frequency of onshore wind can also largely account for the discrepancies between BSI and RI during the period from 2006 to 2019. These findings highlighted the importance of onshore wind anomalies when predicting respiratory irritation impacts along beaches.

Do aggravating rhinologic symptoms at work indicate occupational exposure? A cross-sectional outpatient clinic study.

Air impurities can exacerbate or cause rhinologic diseases. However, only a few studies have assessed rhinologic patients' symptoms at work. This study surveys the impact of work on rhinology clinic patients' quality of life in relation to work-related respiratory exposures. In addition, we surveyed patients' sick leave periods. We recruited adult employed rhinology patients referred to the otorhinolaryngology clinic. A total of 177 patients were included. We collected data on patients' medical history, rhinologic disease-specific and generic quality of life, current or most recent job title, a description of current work, nasal symptoms, possible worked-related symptom triggers and sick leave periods during the preceding year. In total, 101 (57.1%) patients reported exacerbated rhinologic symptoms at work and reported more severe rhinologic disease and a lower disease-specific quality of life compared to non-work-related rhinologic patients (P = 0.008). A minority, 24.3% of our patients were exposed to any specific occupational respiratory sensitizer or irritant at work. The mean sick leave period due to rhinologic disease was 7.7 days per year. Exposure to specific occupational sensitizers or irritants did not associate with increasing symptoms at work or quality of life amongst our patients. Most rhinology patients reported exacerbated symptoms at work. They appeared to be more symptomatic than the rest of the patients and, therefore, possibly hyperreactive to unspecific respiratory triggers at work. Rhinologic diseases caused our patients a marked burden with high work absenteeism.

Beach-level 24-hour forecasts of Florida red tide-induced respiratory irritation

An accurate forecast of the red tide respiratory irritation level would improve the lives of many people living in areas affected by algal blooms. Using a decades-long database of daily beach conditions, two conceptually different models to forecast the respiratory irritation risk level one day ahead of time are trained. One model is wind-based, using the current days’ respiratory level and the predicted wind direction of the following day. The other model is a probabilistic self-exciting Hawkes process model. Both models are trained on beaches in Florida during 2011--2017 and applied to the red tide bloom during 2018-2019. For beaches where there is enough historical data to develop a model, the model which performs best depends on the beach. The wind-based model is the most accurate at half the beaches, correctly predicting the respiratory risk level on average about 84% of the time. The Hawkes model is the most accurate (81% accuracy) at nearly all of the remaining beaches.

Interventions of Unani medicine for maintenance of health with special reference to air quality: an evidence-based review.

This article aims to discuss the impact of air quality on human health, measures to achieve the goal of good indoor air quality and proposed benefits of interventions of Unani Medicine with an evidence-based approach. The significance of air quality on the health of the community cannot be denied. Recent evidences from WHO illustrated data on severe air pollutants and their impacts on human health ranges from minor upper respiratory irritation to chronic respiratory ailments including lung carcinoma and heart disease associated with premature mortality and reduced life expectancy. In Unani Medicine, air has been included in the list of factors, which are six in number and play the central role in prevention of diseases and maintenance of health. Air is considered as the medium of most of the extrinsic factors such as chemical and biological pollutants affecting health and their exposure results in short and long-term health issues. The literature of Unani Medicine proposes many simple and effective measures, which help to improve indoor and outdoor air quality. The goal of outdoor clean air is achieved through implementation of measures to tackle the source of pollution, while indoor clean air is attained through various means e.g., fumigation with herbal drugs. Hence, an extensive literature survey on Unani reserve was conducted to collect information about the concept of air discussed under the heading of six essential factors and its implication in prevention of diseases and maintenance of health. Further, research databases such as Pub Med, Google Scholar, and Science-Direct were broadly searched for evidence on the efficacy of herbals mentioned in Unani literature for the indoor air purification and subsequent air quality improvement. Recent studies showed good air quality leads to decrease in mortality, particularly of respiratory and cardiovascular deaths whereas poor air quality results in a variety of diseases. Unani scholars prescribed several regimens such as Bukhoor (Fumigation), Sa'oot (Nasal instillation) and use of Abeer (Perfumes) and Nadd (Incense) for the improvement of air quality. Likewise various herbal fumigants and sprays containing drugs like mī'a sā'ila (Liquidambar orientalis Mill.), mastagi (Pistacia lentiscus L.), mushk (Moschus moschiferus L.), loban (Styrax benzoides W. G. Craib), ābnoos (Diospyros ebenum J. Koenig ex Retz), zā'fran (Crocus sativus L.) and sirka (vinegar) etc. has been well explained and used exclusively for air purification and improvement of AQI. Therefore, in the present scenario of altered air quality, we forward certain measures described in Unani system of medicine for health promotion and protection. Scientific evidence on several drugs reveal the presence of a number of pharmacologically active substances, which may provide a new approach into the purification of air.

RespiraTox – Development of a QSAR model to predict human respiratory irritants

Respiratory irritation is an important human health endpoint in chemical risk assessment. There are two established modes of action of respiratory irritation, 1) sensory irritation mediated by the interaction with sensory neurons, potentially stimulating trigeminal nerve, and 2) direct tissue irritation. The aim of our research was to, develop a QSAR method to predict human respiratory irritants, and to potentially reduce the reliance on animal testing for the identification of respiratory irritants. Compounds are classified as irritating based on combined evidence from different types of toxicological data, including inhalation studies with acute and repeated exposure.The curated project database comprised 1997 organic substances, 1553 being classified as irritating and 444 as non-irritating. A comparison of machine learning approaches, including Logistic Regression (LR), Random Forests (RFs), and Gradient Boosted Decision Trees (GBTs), showed, the best classification was obtained by GBTs. The LR model resulted in an area under the curve (AUC) of 0.65, while the optimal performance for both RFs and GBTs gives an AUC of 0.71. In addition to the classification and the information on the applicability domain, the web-based tool provides a list of structurally similar analogues together with their experimental data to facilitate expert review for read-across purposes.

Occupational exposure to formaldehyde and oxidative stress in Italian workers

Abstract Background Formaldehyde (FA) is an environmental pollutant widely used in several occupational settings. Beyond its carcinogenic effect, FA can trigger inflammation by promoting reactive oxygen species formation in exposed subjects. The current study aims to investigate the association between air-FA exposure and systemic oxidative stress induction in specific working environments. Methods We accounted for three different scenarios of air-FA exposure by including a sample of pathologists and nurses from operating theatres (n = 185), traffic police officers (n = 154) and wood-workers (n = 127), who participated as volunteers. Exposure to air-FA was assessed by passive air-samplers (Radiello®) and oxidative stress was quantified by 15-F2t-IsoP urinary biomarker (ELISA). A piecewise linear regression model was performed to analyse oxidative stress variation in response to air-FA exposure. Results Overall, 466 subjects (45 ± 9 years) were included in the study, 53% were females. None significant changes of ln(15-F2t-IsoP) were observed before a specific exposure breakpoint of 4.729 (air-FA = 113 µg/m3). Beyond the breakpoint, ln(15-F2t-IsoP) showed a 1.5 increase (p < 0.0001), independently from age and sex. Interestingly, while age did not affect oxidative stress levels nor before neither beyond the breakpoint, sex determined an increase of ln(15-F2t-IsoP) only before the breakpoint (+0.62, p < 0.0001). Conclusions Currently, the most precautionary regulatory limit of air-FA exposure in occupational settings is 0.1 ppm (TLW-TVA, i.e. 120 µg/m3). This limit is recommended to protect for eyes and upper respiratory tract irritation. However, our results highlighted that slightly lower exposures can induce a biological effect, which should deserve consideration from Primary Prevention perspective. Since oxidative stress may evolve in future diseases, it would be advisable considering to tailor the regulatory limits to such a pre-pathological condition rather symptoms onset. Key messages Occupational exposure to air-FA is able to induce systemic oxidative stress even below the regulatory limit, independently from age and sex. Future updates of the regulatory limits in force may consider pre-pathological conditions, such as oxidative stress, rather symptoms onset.

Using localized Twitter activity to assess harmful algal bloom impacts of Karenia brevis in Florida, USA

Red tide blooms of the dinoflagellate Karenia brevis (K. brevis) produce toxic coastal conditions that can impact marine organisms and human health, while also affecting local economies. During the extreme Florida red tide event of 2017–2019, residents and visitors turned to social media platforms to both receive disaster-related information and communicate their own sentiments and experiences. This was the first major red tide event since the ubiquitous use of social media, thus providing unique crowd-sourced reporting of red tide impacts. We evaluated the spatial and temporal accuracy of red tide topic activity on Twitter, taking tweet sentiments and user types (e.g. media, citizens) into consideration, and compared tweet activity with reported red tide conditions, such as K. brevis cell counts, levels of dead fish and respiratory irritation on local beaches. The analysis was done on multiple levels with respect to both locality (e.g., entire Gulf coast, county-level, city-level, zip code tabulation areas) and temporal frequencies (e.g. daily, every three days, weekly), resulting in strong correlations between local per-capita Twitter activity and the actual red tide conditions observed in the area. Moreover, an association was observed between proximity to the affected coastal areas and per-capita counts for relevant tweets. Results show that Twitter presents a trustworthy reflection of the red tide’s local impacts and development over time, and can potentially augment the already existing tools for efficient assessment and a more coordinated response to the disaster.

L’asthme professionnel et l’asthme aggravé par le travail. Quelles différences en termes de facteurs de risque et d’aptitude au travail ?

IntroductionAllergic asthma is currently the most frequent respiratory pathology in the workplace. Whether induced or aggravated by the work environment, the adequacy between this morbid state and work is often subject to re-evaluation. Aim to studyThe socio-professional, clinical, para-clinical and medico-legal characteristics of allergic asthma observed in the workplace, to assess their impact on the ability to work and to compare occupational asthma (OA) and work exacerbated asthma (WEA) in terms of associated professional and extra-professional factors and in terms of repercussions on aptitude. MethodsExhaustive retrospective descriptive study of all work-related allergic asthma files (OA and WEA), collected from the Department of Occupational Medicine and Occupational Pathologies of the University Hospital La Rabta in Tunis during the period from 1 January 2000 to December 31, 2020. ResultsThis is a series of 232 cases of work-related allergic asthma, including 76.7% OA and 23.3% WEA. The mean age of the patients was 40.28±8.96 years. The female gender was represented in 50.9% of cases. A personal history of atopy was reported by 16.5% of patients. The most represented professional category was that of unskilled workers (57.1%) with an average seniority of 11.43±7.96 years. The sectors that provided the most asthma were the textile sector (10%) and the health sector (10.9%). The clinical symptoms were dominated by paroxysmal wheezing dyspnea (51.5%), punctuated by work. in the majority (86.6%). The responsible agents were high molecular weight allergens (HMW) in particular vegetable textile dust (9.9%), low molecular weight (LMW) such as isocyanate (11.6%), formaldehyde (11.2%) as well as respiratory irritants, mainly mold (7.8%) and non-specific dust (3.9%). Asthma justified a workstation adaptation in 47.8% of cases and a mutation in 40.9% of patients.Comparing the cases of work-induced asthma with those that were exacerbated, we found that age and length of service were higher in the OA group, (P=0.002) and (P=0.005). In addition, this group was also associated with the grade of unskilled worker (P=0.035), exposure to HMW allergens (P=0.008), as well as the prescription for a job transfer (P≤10-3). In addition, WEA was associated with a history of personal and family atopy with respectively (P≤10–3) and (P=0.017), work in the transport sector (P≤10-3) as well as prescription temporary unfitness for the post (P≤10–3). ConclusionThe etiologies of OA and WEA differ. Indeed, the etiologies of WEA are essentially respiratory irritants while in the OA are HMW allergens. In terms of aptitude, the impact on OA is more pejorative than WEA involving more mutation.

Serum intracellular adhesion molecule-1 and interleukin-8 as predictors of pulmonary impairment among workers in secondary copper smelters

Copper smelter workers are exposed to harmful chemical agents in dust and fumes which contain harmful metals such as copper and arsenic. These substances are known to be respiratory irritants. This study aimed at investigating the effect of occupational exposure to copper and arsenic on the respiratory system. A group of 75 male exposed workers, and 75 male administrative employees (control group) were recruited from a secondary copper smelting factory. Full history, complete clinical examination, ventilatory function parameters (FVC, FEV1, FVC/FEV1 and FEF), and chest X-ray were done for both groups. Serum levels of ICAM-1 and IL8 (as markers of epithelial injury) were measured by ELISA. Serum copper and arsenic were measured by atomic absorption spectrophotometer. The exposed group was associated with increased respiratory symptoms, higher serum copper, arsenic, and ICAM-1and Il-8 as compared to the control group. There was a significant decrease in ventilatory parameters among the exposed group: 58.7% of the exposed group had restrictive lung impairment, 40% had obstructive impairment. In the exposed group a positive correlation between serum copper, arsenic and serum ICAM and IL8 was found. While a negative correlation was observed between both serum ICAM, IL8 and ventilatory parameters among the exposed group. Moreover, 36% of the exposed group had radiological infiltrates on chest X.ray. Occupational exposure to copper and arsenic was associated with ventilatory and radiological impairment, with a corresponding increase in the serum level of ICAM-1 and IL8, which can be used as biomarkers for pulmonary impairment among copper smelter workers.

Отравление селеном и его соединениями в промышленности и быту

Селен — химический элемент с атомным номером 34. Обозначается символом Se. Селен — необходимый для жизни микроэлемент. Обладает выраженными антиоксидантными и антиканцерогенными свойствами. Принимает участие во многих процессах в организме, чем обеспечивает функционирование иммунной и эндокринной систем. Влияет на физическое и умственное развитие у детей. Пища является основным источником селена для человека. В промышленности селен получают как побочный продукт переработки меди. Его используют в электронных полупроводниках, как обесцвечивающее вещество для керамики и стекла, как вулканизирующее вещество в производстве шин. Селен применяется в фармакологии, как антиканцерогенное средство. Соли селена легко всасываются слизистыми оболочками желудочно-кишечного тракта. В крови селен связывается с гемоглобином, образуется селенгемоглобин, в результате возникает гемическая гипоксия. В тканях селен вытесняет серу из серосодержащих аминокислот, нарушаются окислительно-восстановительные процессы. Селениты как активные антиоксиданты уменьшают активность глутатионпероксидазы и глутатионредуктазы и блокируют метаболизм глутатиона. Замена S-S связей селенотрисульфидными комплексами приводит к изменению третичной структуры белков и нарушает их функцию. В больших дозах селен вызывает отравление — селенизм. Для человека токсическая доза селена составляет 5 мг. Обладает политропным действием с преимущественным поражением печени, почек и центральной нервной системы. Острые тяжелые ингаляционные отравления протекают бурно и фульминантно. После вдыхания паров селена в больших концентрациях наблюдается потеря сознания и состояние коллапса. Характерным является чесночный запах изо рта. При ингаляционном пути поступления селена в концентрации 1–4 мкг/л описана клиника раздражения верхних дыхательных путей с развитием токсического отека легких и пневмонии. Наблюдаются явления гастроэнтерита, энцефаломиелита, анорексии, влажный и себорейный дерматит. Хроническая интоксикация селеном напоминает мышьяковую интоксикацию. Характерно снижение массы тела, апатия, усталость, мигрень, головокружение, тошнота, рвота, диарея, тяжесть в области правого подреберья, хронические бронхиты, гипохромная анемия; также выпадение волос, белые горизонтальные полосы на ногтях рук, паронихия, раздражительность, гиперрефлексия, чесночный запах при дыхании и металлический привкус во рту; болезненная чувствительность мышц, тремор, головокружение и покраснение лица. Лечение включает в себя введение антидотов, промывание слизистых оболочек, противошоковые мероприятия и симптоматическую терапию.

Towards sustainable additive manufacturing: The need for awareness of particle and vapor releases during polymer recycling, making filament, and fused filament fabrication 3-D printing

Fused filament fabrication three-dimensional (FFF 3-D) printing is thought to be environmentally sustainable; however, significant amounts of waste can be generated from this technology. One way to improve its sustainability is via distributed recycling of plastics in homes, schools, and libraries to create feedstock filament for printing. Risks from exposures incurred during recycling and reuse of plastics has not been incorporated into life cycle assessments. This study characterized contaminant releases from virgin (unextruded) and recycled plastics from filament production through FFF 3-D printing. Waste polylactic acid (PLA) and acrylonitrile butadiene styrene (ABS) plastics were recycled to create filament; virgin PLA, ABS, high and low density polyethylenes, high impact polystyrene, and polypropylene pellets were also extruded into filament. The release of particles and chemicals into school classrooms was evaluated using standard industrial hygiene methodologies. All tasks released particles that contained hazardous metals (e.g., manganese) and with size capable of depositing in the gas exchange region of the lung, i.e., granulation of waste PLA and ABS (667 to 714 nm) and filament making (608 to 711 nm) and FFF 3-D printing (616 to 731 nm) with waste and virgin plastics. All tasks released vapors, including respiratory irritants and potential carcinogens (benzene and formaldehyde), mucus membrane irritants (acetone, xylenes, ethylbenzene, and methyl methacrylate), and asthmagens (styrene, multiple carbonyl compounds). These data are useful for incorporating risks of exposure to hazardous contaminants in future life cycle evaluations to demonstrate the sustainability and circular economy potential of FFF 3-D printing in distributed spaces.

In silico approaches in organ toxicity hazard assessment: Current status and future needs for predicting heart, kidney and lung toxicities

The kidneys, heart and lungs are vital organ systems evaluated as part of acute or chronic toxicity assessments. New methodologies are being developed to predict these adverse effects based on in vitro and in silico approaches. This paper reviews the current state of the art in predicting these organ toxicities. It outlines the biological basis, processes and endpoints for kidney toxicity, pulmonary toxicity, respiratory irritation and sensitization as well as functional and structural cardiac toxicities. The review also covers current experimental approaches, including off-target panels from secondary pharmacology batteries. Current in silico approaches for prediction of these effects and mechanisms are described as well as obstacles to the use of in silico methods. Ultimately, a commonly accepted protocol for performing such assessment would be a valuable resource to expand the use of such approaches across different regulatory and industrial applications. However, a number of factors impede their widespread deployment including a lack of a comprehensive mechanistic understanding, limited in vitro testing approaches and limited in vivo databases suitable for modeling, a limited understanding of how to incorporate absorption, distribution, metabolism, and excretion (ADME) considerations into the overall process, a lack of in silico models designed to predict a safe dose and an accepted framework for organizing the key characteristics of these organ toxicants.

Human risk assessment of inhaled irritants: Role of sensory stimulations from spatially separated nociceptors

Contemporary approaches to human health risk assessment for respiratory tract irritants are variable and controversial. This manuscript provides an in-depth analysis and assessment of the applicability of the classical respiratory depression 50 % (RD50) assay with focus on the Log-linear extrapolation of the non-sensory irritant threshold (RD0 or RD10) relative to the contemporary Point of Departure (POD) U.S.-EPA benchmark approach. Three prototypic volatile chemically reactive irritants are used to exemplify the pros and cons of this alternative approach. These irritants differ in physicochemical properties affecting water-solubility and lipophilicity. Depending on these variables, a vapor may preferentially be retained in the extrathoracic region (ET), the tracheobronchial region (TB), and the pulmonary region (PU); although a smooth transition between these regions occurs at increasingly high concentrations. Each region has its specific nociceptors sensing irritants and regional-specific response to injury. The alternative approach using rats identified the chemical-specific critical region of respiratory tract injury. Statistically derived PODs on ET-TB related sensory irritation provide important information for ET-TB irritants but not for PU irritants. The POD of ET-TB irritants from acute and repeated studies decreased substantially. In summary, statistically derived PODs improve the risk assessment of respiratory tract irritants; however, those from repeated exposures should be given preference to those from acute exposures.

Nasopulmonary mites (Halarachnidae) of coastal Californian pinnipeds: Identity, prevalence, and molecular characterization

Mites from the family Halarachnidae Oudemans 1906 are obligate endoparasites that colonize the respiratory tracts of free-living and captive marine mammals. Infestations can range from mild to severe and result in respiratory tract irritation or impairment. Nasopulmonary acariasis was determined to be a contributing cause of death among several southern sea otters Enhydra lutris nereis Merriam 1904 in a longitudinal study of otter mortality, and proximity to Pacific harbor seals Phoca vitulina richardii Gray 1864 was a significant risk factor for sea otter infestation. Beyond scattered opportunistic reports, each halarachnid mite species' affinity for particular hosts and the extent of mite transmission between host species is poorly understood. We investigated the identity and prevalence of nasopulmonary mites from Pacific harbor seals, California sea lions Zalophus californianus Lesson 1828, northern elephant seals Mirounga angustirostris Gill 1866, northern fur seals Callorhinus ursinus Linnaeus 1758, and Guadalupe fur seals Arctocephalus philippii townsendi Merriam 1897 to complement published nasopulmonary mite findings from sympatric southern sea otters during a comparable timeframe. Halarachnid mite infestation was common among California sea lions (74.1%), northern fur seals (73.3%), and northern elephant seals (46.6%), but was less common among harbor seals (18.7%) and Guadalupe fur seals (8.8%). Observed host-mite relationships suggest a distinct host specificity, with genus Orthohalarachne infesting otariids, and genus Halarachne infesting phocids and lutrinids along the California coast. Harbor seals and southern sea otters were the primary hosts of H. halichoeri, but one nothern elephant seal was infested with both H. miroungae and a single H. halichoeri. We also present the first high-resolution SEM images for H. miroungae and O. attenuata and possible evidence for a new host record for H. halichoeri.