Biological effects of inhaled hydraulic fracturing sand dust. II. Particle characterization and pulmonary effects 30 d following intratracheal instillation.

Hydraulic fracturing ("fracking") is used in unconventional gas drilling to allow for the free flow of natural gas from rock. Sand in fracking fluid is pumped into the well bore under high pressure to enter and stabilize fissures in the rock. In the process of manipulating the sand on site, respirable dust (fracking sand dust, FSD) is generated. Inhalation of FSD is a potential hazard to workers inasmuch as respirable crystalline silica causes silicosis, and levels of FSD at drilling work sites have exceeded occupational exposure limits set by OSHA. In the absence of any information about its potential toxicity, a comprehensive rat animal model was designed to investigate the bioactivities of several FSDs in comparison to MIN-U-SIL® 5, a respirable α-quartz reference dust used in previous animal models of silicosis, in several organ systems (Fedan, J.S., Toxicol Appl Pharmacol. 00, 000-000, 2020). The present report, part of the larger investigation, describes: 1) a comparison of the physico-chemical properties of nine FSDs, collected at drilling sites, and MIN-U-SIL® 5, a reference silica dust, and 2) a comparison of the pulmonary inflammatory responses to intratracheal instillation of the nine FSDs and MIN-U-SIL® 5. Our findings indicate that, in many respects, the physico-chemical characteristics, and the biological effects of the FSDs and MIN-U-SIL® 5 after intratracheal instillation, have distinct differences.

Occupational Exposures and Cardiac Structure and Function: ECHO-SOL (Echocardiographic Study of Latinos).

Background Our objective was to determine associations of occupational exposures with cardiac structure and function in Hispanic/Latino adults. Methods and Results Employed participants were included (n=782; 52% women, mean age 52.9 years). Occupational exposures to burning wood, vehicle exhaust, solvents, pesticides, and metals at the current and longest-held job were assessed by questionnaire. Survey multivariable linear regression analyses were used to model the relationship of each self-reported exposure with echocardiographic measures of cardiac structure and function. Exposure to burning wood at the current job was associated with decreased left ventricular (LV) ejection fraction (-3.1%; standard error [SE], 1.0 [P=0.002]). When the analysis was restricted to exposure at the longest-held job, occupational exposure to burning wood was associated with increased LV diastolic volume (6.7 mL; SE, 1.6 [P<0.0001]), decreased LV ejection fraction (-2.7%; SE, 0.6 [P<0.0001]), worse LV global longitudinal strain (1.0%; SE, 0.3 [P=0.0009]), and decreased right ventricular fractional area change (-0.02; SE, 0.004 [P<0.001]). Exposure to pesticides was associated with worse average global longitudinal strain (0.8%; SE, 0.2 [P<0.0001]). Exposure to metals was associated with worse global longitudinal strain in the 2-chamber view (1.0%; SE, 0.5 [P=0.04]), increased stroke volume (3.6 mL; SE, 1.6 [P=0.03]), and increased LV mass indexed to BSA (9.2 g/m2; SE, 3.8 [P=0.01]) or height (4.4 g/m2.7; SE, 1.9 [P=0.02]). Conclusions Occupational exposures to burning wood, vehicle exhaust, pesticides, and metals were associated with abnormal parameters of LV and right ventricular systolic function. Reducing exposures to toxic chemicals and particulates in the workplace is a potential opportunity to prevent cardiovascular disease in populations at risk.

Bisphenols and Male Reproductive Health: From Toxicological Models to Therapeutic Hypotheses.

Bisphenols, and in particular bisphenol A (BPA), have been widely used for the production of plastic manufacts in the last 50 years. Currently, BPA is present in a variety of daily use polycarbonate plastics and epoxy resins, and dietary ingestion is considered the main route of human exposure. Accordingly, BPA is the chemical pollutant with the widest exposure in humans, involving nearly 90% of general population, according to recent studies. Concerns about BPA effects on human health date back to 1930s, when severe impact on male sexual development was suggested. Now, the acknowledged biological effects of BPA are various. In regard to human fertility, BPA has been shown to disrupt hormone signaling even at low concentrations. Results from human epidemiological studies have reported BPA interference with follicle stimulating hormone, inhibin B, estradiol, testosterone levels, and sexual function in male subjects. Moreover, recent studies have reported an association between BPA levels and reduced sperm concentration, motility, normal morphology, sperm DNA damage, and altered epigenetic pattern, resulting in trans-generational legacy of BPA effects. In this review, the recognized effects of BPA on male reproductive health are described, from the most recent issues on experimental models to epidemiological data. In addition, the very recent interest about the use of nutraceutical remedies to counteract BPA effects are discussed.

Bisphenol a Exposure in Utero Disrupts Hypothalamic Gene Expression Particularly Genes Suspected in Autism Spectrum Disorders and Neuron and Hormone Signaling.

Bisphenol A (BPA) is an endocrine-disrupting compound detected in the urine of more than 92% of humans, easily crosses the placental barrier, and has been shown to influence gene expression during fetal brain development. The purpose of this study was to investigate the effect of in utero BPA exposure on gene expression in the anterior hypothalamus, the basal nucleus of the stria terminalis (BNST), and hippocampus in C57BL/6 mice. Mice were exposed in utero to human-relevant doses of BPA, and then RNA sequencing was performed on male PND 28 tissue from whole hypothalamus (n = 3/group) that included the medial preoptic area (mPOA) and BNST to determine whether any genes were differentially expressed between BPA-exposed and control mice. A subset of genes was selected for further study using RT-qPCR on adult tissue from hippocampus to determine whether any differentially expressed genes (DEGs) persisted into adulthood. Two different RNA-Seq workflows indicated a total of 259 genes that were differentially expressed between BPA-exposed and control mice. Gene ontology analysis indicated that those DEGs were overrepresented in categories relating to mating, cell-cell signaling, behavior, neurodevelopment, neurogenesis, synapse formation, cognition, learning behaviors, hormone activity, and signaling receptor activity, among others. Ingenuity Pathway Analysis was used to interrogate novel gene networks and upstream regulators, indicating the top five upstream regulators as huntingtin, beta-estradiol, alpha-synuclein, Creb1, and estrogen receptor (ER)-alpha. In addition, 15 DE genes were identified that are suspected in autism spectrum disorders.

The time-dependent health and biochemical effects in rats exposed to stainless steel welding dust and its soluble form.

Welding processes that generate fumes containing toxic metals, such as hexavalent chromium (Cr(VI)), manganese (Mn), and nickel (Ni), have been implicated in lung injury, inflammation, and lung tumor promotion in animal models. The principal objective of this study was to determine the dynamics of toxic effects of inhalation exposure to morphologically rated welding dust from stainless steel welding and its soluble form in TSE System with a dynamic airflow. We assessed the pulmonary toxicity of welding dust in Wistar rats exposed to 60.0 mg/m3 of respirable-size welding dust (mean diameter 1.17 µm) for 2 weeks (6 h/day, 5 days/week); the aerosols were generated in the nose-only exposure chambers (NOEC). An additional aim included the study of the effect of betaine supplementation on oxidative deterioration in rat lung during 2 weeks of exposure to welding dust or water-soluble dust form. The animals were divided into eight groups (n = 8 per group): control, dust, betaine, betaine + dust, soluble-form dust, soluble-form dust + betaine, saline and saline + betaine groups. Rats were euthanized 1 or 2 weeks after the last exposure for assessment of pulmonary toxicity. Differential cell counts, total protein concentrations and cellular enzyme (lactate dehydrogenase-LDH) activities were determined in bronchoalveolar lavage (BAL) fluid, and corticosterone and thiobarbituric acid reactive substances (TBARS) concentrations were assessed in serum. The increase in polymorphonuclear (PMN) leukocytes in BAL fluid (a cytological index of inflammatory responses of the lung) is believed to reflect pulmonary toxicity of heavy metals. Biomarkers of toxicity assessed in bronchoalveolar fluids indicate that the level of the toxic effect depends mainly on the solubility of studied metal compounds; biomarkers that showed treatment effects included: total cell, neutrophil and lymphocyte counts, total protein concentrations, and cellular enzyme (lactate dehydrogenase) activity. Betaine supplementation at 250 mg/kg/day in all study rats groups attenuated stress indices, and corticosterone and TBARS serum levels, and simultaneously stimulated increase of polymorphonuclear cells in BALF of rats. The study confirmed deleterious effect of transitory metals and particles during experimental inhalation exposure to welding dusts, evidenced in the lungs and brain by increased levels of total protein, higher cellular influx, rise of LDH in BALF, elevated TBARS and increased corticosterone in serum of rats. Our result confirm also the hypothesis about the effect of the welding dusts on the oxidative stress responsible for disturbed systemic homeostasis and impairment of calcium regulation.

Work-related symptoms among workers exposed to black tea dust.

BACKGROUND: Tea may be classified as unfermented green, semi-ferinented oolong and fermented black. All of these types are derived from Camellia sinensis, the Tea Plant, which contains the low molecular weight (LMW) agent Epigallocatechin gallate (EGCg), probably responsible for allergic reactions. The aim of our study was to asses the work-related allergic symptoms and IgE-mediated sensitivity among black tea packers. MATERIAL AND METHODS: Study groups comprised 26 black tea packers (group 1) and 20 office workers (group 2). A questionnaire, skin prick tests (SPTs) to common allergens and black tea, evaluation of specific IgE (asIgF) to Camellia sinensis and moulds, pre- and post-work-shift spirometry were performed. RESULTS: At least I symptom suggesting allergic disease was reported by 85% of the tea packers and 60% of the office workers. The most frequent positive results of SPTs were obtained with moulds (8%). A small decline in FE%1 (forced expiratory volume in I s) after the work shift was observed among tea packers sensitized to moulds. CONCLUSIONS: Although specific sensitization to black tea was not observed in our study groups, cough and skin symptoms were significantly more frequently among the tea packers than in office workers. The irritant impact on the airways and the skin of tea dust and/or sensitization to moulds contaminating tea leaves are being suspected.

Airway symptoms and lung function among male workers in an area polluted from an oil tank explosion.

OBJECTIVE: To assess whether working in an industrial harbor where an oil tank exploded was associated with more airway symptoms and lower lung function in men 1.5 years later. METHODS: In a cross-sectional study of 180 men, 18 to 67 years old, airway symptoms and lung function among men who worked in the industrial harbor at the time of the explosion was compared with those of working men with residence more than 20 km away. Regression analyses are adjusted for smoking, occupational exposure, atopy, recent infection, and age. RESULTS: Exposed men had significantly more upper (ORirritated nose = 2.89 [95% confidence interval = 1.31 to 6.37]) and lower (ORdyspnea uphill = 3.79 [95% confidence interval = 1.69 to 8.46]) airway symptoms, and some indication of more reversible airway obstruction than unexposed workers. CONCLUSIONS: Men working in an area with an oil tank explosion had more airway symptoms and indication of more airway obstruction 1.5 years after the event.

Bauxite mining and alumina refining: process description and occupational health risks.

OBJECTIVE: To describe bauxite mining and alumina refining processes and to outline the relevant physical, chemical, biological, ergonomic, and psychosocial health risks. METHODS: Review article. RESULTS: The most important risks relate to noise, ergonomics, trauma, and caustic soda splashes of the skin/eyes. Other risks of note relate to fatigue, heat, and solar ultraviolet and for some operations tropical diseases, venomous/dangerous animals, and remote locations. Exposures to bauxite dust, alumina dust, and caustic mist in contemporary best-practice bauxite mining and alumina refining operations have not been demonstrated to be associated with clinically significant decrements in lung function. Exposures to bauxite dust and alumina dust at such operations are also not associated with the incidence of cancer. CONCLUSIONS: A range of occupational health risks in bauxite mining and alumina refining require the maintenance of effective control measures.

Exposures and cross-shift lung function declines in wildland firefighters.

Respiratory problems are common among wildland firefighters. However, there are few studies directly linking occupational exposures to respiratory effects in this population. Our objective was to characterize wildland fire fighting occupational exposures and assess their associations with cross-shift changes in lung function. We studied 17 members of the Alpine Interagency Hotshot Crew with environmental sampling and pulmonary function testing during a large wildfire. We characterized particles by examining size distribution and mass concentration, and conducting elemental and morphological analyses. We examined associations between cross-shift lung function change and various analytes, including levoglucosan, an indicator of wood smoke from burning biomass. The levoglucosan component of the wildfire aerosol showed a predominantly bimodal size distribution: a coarse particle mode with a mass median aerodynamic diameter about 12 µm and a fine particle mode with a mass median aerodynamic diameter < 0.5 µm. Levoglucosan was found mainly in the respirable fraction and its concentration was higher for fire line construction operations than for mop-up operations. Larger cross-shift declines in forced expiratory volume in one second were associated with exposure to higher concentrations of respirable levoglucosan (p < 0.05). Paired analyses of real-time personal air sampling measurements indicated that higher carbon monoxide (CO) concentrations were correlated with higher particulate concentrations when examined by mean values, but not by individual data points. However, low CO concentrations did not provide reliable assurance of concomitantly low particulate concentrations. We conclude that inhalation of fine smoke particles is associated with acute lung function decline in some wildland firefighters. Based on short-term findings, it appears important to address possible long-term respiratory health issues for wildland firefighters. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resources: a file containing additional information on historical studies of wildland fire exposures, a file containing the daily-exposure-severity questionnaire completed by wildland firefighter participants at the end of each day, and a file containing additional details of the investigation of correlations between carbon monoxide concentrations and other measured exposure factors in the current study.].

[Aerogenic risk factors and diagnosis of bauxite pneumoconiosis].

The research purpose is an estimation of influence of the bauxite dust on the state of the bronchopulmonary system of workers. It has been indicated that exposure of the poor fibrogenic dust while the process of the bauxite ore extraction, results in development of pnevmokoniosis characterized by substantial ventilatory and haemodynamic disorders limiting the workability of patients.

Respiratory symptoms, exhaled nitric oxide, and lung function among workers in Tanzanian coffee factories.

OBJECTIVE: To compare chronic respiratory symptoms, fractional exhaled nitric oxide (FENO), and lung function between Robusta and Arabica coffee workers and a control group. METHODS: Chronic respiratory symptoms were assessed by a questionnaire (n = 138 coffee workers and n = 120 controls). The FENO was measured by NIOX MINO device (Aerocrine AB, Solna, Sweden). Lung function was examined by a portable spirometer. RESULTS: Coffee workers had higher prevalence of chronic respiratory and asthma symptoms than controls. Robusta coffee workers were exposed to higher levels of endotoxin and had more asthma symptoms than Arabica coffee workers (38% vs. 18%). Coffee workers had reduced lung function associated with cumulative exposure to total dust and endotoxin. CONCLUSION: Work in coffee factories is associated with small but significant lung function impairment. These changes were not associated with the level of FENO.

[Factors of work environment and employment of workers in production of fuels and solvents at the oil refinery].

THEME: Factors of the industrial environment and labor activity of workers of manufacture propellants and solvents at the oil refining enterprise. OBJECT OF RESEARCH: Working conditions of workers at all installations of manufacture No 1 JSC "Naftan" of Novopolotsk of Byelorussia (production of fuels and solvents). THE AIM: Hygienic evaluation of working conditions of persons working in the production of fuels and solvents at the oil refinery. METHODS: Sanitary description of the production with hygienic analysis of project design and technological documentation, qualitative and quantitative characteristics of conventional methods in the work environment and working process of employees in the workplace for the main modes of operation of the equipment. THEORETICAL AND EXPERIMENTAL RESULTS: The working environment of refineries is influenced by a number of simultaneously acting factors, which have different material nature and characteristics of the action on the human body, the workers in production of fuels and solvents at the refinery, are exposed to a variety of hazardous and dangerous factors of production, a chemical factor is prevalent, of course.

Therapeutic associated with occupational exposure to silica.

Occupational exposure to silica dust has been increasing the possible risk of varieties of pathologies. The aim of this study was to evaluate the protective activity of ethanolic extract of Glycyrrhiza glabra roots at doses of 500 and 1000 mg/kg, p.o., given for 7 days against the toxicity of SiO(2) nanoparticles (50mg/kg intraperitoneal for 6 weeks) in rats. Exposure to silica altered various respiratory and biochemical variables, including ALT, AST, albumin, urea, uric acid, creatinine, catalase, LPO and GSH. Treatments with G. glabra extract significantly improved antioxidant status towards control. Stone workers in the Gwalior region exposed to silica dust had higher prevalence of cough, wheezing and shortness of breath. Increased serum ACE level was noted in the silica exposed group. It is of immense need to monitor this problem for betterment of worker's health.

3D-modelling of radon-induced cellular radiobiological effects in bronchial airway bifurcations: direct versus bystander effects.

PURPOSE: The primary objective of this paper was to investigate the distribution of radiation doses and the related biological responses in cells of a central airway bifurcation of the human lung of a hypothetical worker of the New Mexico uranium mines during approximately 12 hours of exposure to short-lived radon progenies. MATERIALS AND METHODS: State-of-the-art computational modelling techniques were applied to simulate the relevant biophysical and biological processes in a central human airway bifurcation. RESULTS: The non-uniform deposition pattern of inhaled radon daughters caused a non-uniform distribution of energy deposition among cells, and of related cell inactivation and cell transformation probabilities. When damage propagation via bystander signalling was assessed, it produced more cell killing and cell transformation events than did direct effects. If bystander signalling was considered, variations of the average probabilities of cell killing and cell transformation were supra-linear over time. CONCLUSIONS: Our results are very sensitive to the radiobiological parameters, derived from in vitro experiments (e.g., range of bystander signalling), applied in this work and suggest that these parameters may not be directly applicable to realistic three-dimensional (3D) epithelium models.

A newly developed scavenging system for administration of nitrous oxide during labour: safe occupational use.

OBJECTIVE: Nitrous oxide (N(2) O) is routinely used as an analgesic in obstetrics during labour. Epidemiological studies have linked chronic occupational exposure to N(2) O to specific health problems, including reproductive risks. Occupational exposure limits (OELs) allow the use of N(2) O once appropriate preventive and safety measures have been taken. We assessed the effectiveness of a scavenger system (Anevac P-system®, Medicvent Heinen & Löwestein Benelux, Barneveld, the Netherlands) applied in N(2) O administration during labour in a midwifery-led birthing centre in the Netherlands. METHODS: After informed consent, non-pregnant midwives were trained to administer N(2) O. N(2) O was delivered as a 50 : 50 mixture with oxygen and was self administered by the patient. The scavenging device, containing a double mask and a chin mask, was connected to the local evacuation system vented outside the building. Data on the 8-h time-weighted average (8-h TWA) as well as the 15-min TWA (15-min TWA) were obtained. RESULTS: Thirteen patients were included. Six patients were included in the first study period. In this period the 8-h TWA was not exceeded, however, in all patients, the 15-min TWA occasionally exceeded the OELs. After four additional measures, seven patients were included. After implementation of these measures, the 8-h TWA and 15-min TWA never exceeded the OELs. System leakage was not observed during both study periods. CONCLUSION: The Anevac P-scavenging system during N(2) O analgesia in labour prevents exceeding OELs in professional workers. The scavenging system appeared acceptable and effective, and can be considered in hospital settings that use N(2) O as analgesic during labour.

Multimodal event-related potentials in occupational chronic solvent encephalopathy.

The aim of this study was to test a multimodal event-related potential (ERP) paradigm in chronic solvent encephalopathy (CSE) to develop a sensitive method for the clinical diagnostics to CSE. The study comprised 11 CSE patients and 13 healthy controls. We used three tasks: an auditory odd-ball (AUD), a visual detection (VIS), and a recognition memory (MEM) task. The auditory and visual stimuli were presented in single- and dual-task conditions. The auditory P300 amplitude in single-task condition was smaller in the patient group than in the control group at the parietal (Pz) but not at the frontal midline electrode location. The auditory P300 response in the dual task condition AUD+VIS was unrecognizable in 8 of 11 patients and in 1 of 13 controls and in the AUD+MEM condition in 10 of 11 patients and in 4 of 13 controls. In the AUD+MEM condition, the auditory P300 amplitude at Pz was smaller in the patient group than in the control group. Reaction time for auditory stimuli in both dual conditions as well as for visual stimuli in AUD+VIS condition were in the patient group prolonged. The ERP results indicate that CSE patients present with slowed performance speed and difficulties in allocation of attention. Based on ERP results, the disturbance in brain activity in CSE seems to affect posterior aspects of the frontoparietal continuity. The multimodal paradigm seems promising as a tool for the clinical diagnostics of CSE.

Use of the reciprocal calculation procedure for setting workplace emergency action levels for hydrocarbon mixtures and their relationship to lower explosive limits.

This paper proposes a novel use of the reciprocal calculation procedure (RCP) to calculate workplace emergency action levels (WEALs) for accidental releases of hydrocarbon mixtures. WEALs are defined here as the concentration in air that area monitors should alarm at to provide adequate warning and be sufficiently protective of health to allow at least enough time to don respiratory protective equipment (RPE) and escape. The rationale for the approach is analysed, and ways of defining suitable substance group guidance values (GVs) for input into the RCP are considered and compared. WEAL GVs could be based on: 3× RCP GVs (i.e. using the 3× rule), the 5× RCP GVs (i.e. using the 5× rule for calculating ceiling values), emergency exposure limits, or immediately dangerous to life or health values (IDLHs). Of these, the method of choice is to base WEAL GVs on health-based IDLH values, which were developed for emergency situations in the workplace. However, IDLHs have only been set for 11 hydrocarbons, so the choice of GVs is also informed by comparison with possible GVs based on the other approaches. Using the proposed GVs, WEALs were calculated for various hydrocarbon mixtures, and the way they vary with the composition of the mixture was examined. Also, the level of health protection given by the current practice of setting emergency area alarms in the oil and gas industry at 10% of the lower explosive limit (LEL) was tested by comparing this with the WEAL. In the event of an accidental release, this comparison suggests that, provided that aromatics constitute <50% of the mixture, an alarm set at 10% LEL should provide adequate warning and be sufficiently protective of health to at allow at least enough time to don RPE and escape. In the absence of better information or specific acute toxicity concerns (such as the presence of hydrogen sulphide), it is proposed that the WEALs be used as a guide for assessing the adequacy of area alarm levels in respect of warning of an acute health risk. This work is exploratory (e.g. other rationales for setting GVs are possible) and the approach needs testing on further real-life samples. Although not explored here, the RCP approach may also lend itself to the calculation of in-house short-term exposure limits for hydrocarbon mixtures and other mixtures where the acute toxic end points of the components are similar.