Acute Inhalation Research Articles

E-cigarettes and their lone constituents induce cardiac arrhythmia and conduction defects in mice

E-cigarette use has surged, but the long-term health effects remain unknown. E-cigarette aerosols containing nicotine and acrolein, a combustion and e-cigarette byproduct, may impair cardiac electrophysiology through autonomic imbalance. Here we show in mouse electrocardiograms that acute inhalation of e-cigarette aerosols disturbs cardiac conduction, in part through parasympathetic modulation. We demonstrate that, similar to acrolein or combustible cigarette smoke, aerosols from e-cigarette solvents (vegetable glycerin and propylene glycol) induce bradycardia, bradyarrhythmias, and elevations in heart rate variability during inhalation exposure, with inverse post-exposure effects. These effects are slighter with tobacco- or menthol-flavored aerosols containing nicotine, and in female mice. Yet, menthol-flavored and PG aerosols also increase ventricular arrhythmias and augment early ventricular repolarization (J amplitude), while menthol uniquely alters atrial and atrioventricular conduction. Exposure to e-cigarette aerosols from vegetable glycerin and its byproduct, acrolein, diminish heart rate and early repolarization. The pro-arrhythmic effects of solvent aerosols on ventricular repolarization and heart rate variability depend partly on parasympathetic modulation, whereas ventricular arrhythmias positively associate with early repolarization dependent on the presence of nicotine. Our study indicates that chemical constituents of e-cigarettes could contribute to cardiac risk by provoking pro-arrhythmic changes and stimulating autonomic reflexes.

Toxicological and hygienic requirements when working with pesticides in agriculture

Intensive use of pesticides in Russia puts forward the task of identifying ways to prevent their adverse effects on the health of workers. The purpose of the study is to substantiate the safety requirements when working with pesticides in agriculture from a toxicological and hygienic standpoint. An analytical study was performed. Research materials documents regulating the use of pesticides, scientific publications, data from own research. The safety of pesticides for those working with them is based on numerous toxicological and hygienic studies carried out at the stage of registration tests. According to the results of toxicological studies, including the establishment of toxicity parameters for acute inhalation, dermal and oral intake, subacute and chronic exposure, in accordance with the hygienic classification of pesticides by degree of danger, a hazard class is established, which determines the possibility, scale, technology of the use of pesticides on the territory of the Russian Federation. Particular attention is paid to the study of sensitizing effects, irritating effects on the skin and mucous membranes, as well as possible manifestations of long-term effects (teratogenic, embryotoxic, carcinogenic, mutagenic). The severity of carcinogenic and mutagenic effects determines the restriction of the use of pesticides, up to a complete ban. Hygienic regulation of the content of active substances of pesticides is carried out taking into account the hazard class and toxicity parameters. A prerequisite for the safe use of pesticides is the establishment of hygienic standards in almost all environments. The last stage of the study is an assessment of the risk to workers when using each pesticide in real conditions of agricultural production and regulation of use. Conclusion. Safety requirements for those working with pesticides when applied using various technologies in agricultural conditions are determined taking into account the hazard class of pesticides and the equipment used. The application of the method of assessing the risk of exposure to pesticides at the stage of registration tests guarantees the exclusion from circulation in Russia of drugs that pose a real danger to a working person. The minimum risk of exposure to pesticides on workers is ensured by compliance with all safety requirements and application regulations.

Dimethyl ether (DME).

The WEEL guide for dimethyl ether (DME) was originally established in 1996 and updated in 2010. Literature searches to identify new toxicity information were performed in November 2020 and evaluated by the WEEL Revisions Subcommittee. No new studies or data relevant to the WEEL guide were identified. DME has very low acute inhalation toxicity with a 4 h LC50 in rats of 164,000 ppm, and a cardiac sensitization threshold in dogs of >200,000 ppm. In repeated inhalation studies of up to 2 years in the rat, DME was not carcinogenic and produced minimal toxicity at 25,000 and 10,000 ppm: the NOAEC was 2000 ppm. DME was not teratogenic in pregnant rats up to 40,000 ppm; slight maternal and fetal toxicity were observed at >5000 ppm. DME was not mutagenic in vitro or in vivo. The primary finding with inhalation exposure was a reversible CNS depression. Based on a clear NOAEC of 2000 ppm for all effects in a lifetime inhalation study in rats, and the general low level of toxicity found in acute and subchronic toxicity studies, a WEEL of 1000 ppm (v/v; 8-h time-weighted average) was reaffirmed in 2021 and should provide an adequate margin of safety.

TOXICOLOGICAL AND HYGIENIC ASSESSMENT OF THE NEW ACTIVE INGREDIENT OF THE AVERSECTINS CLASS - MILBEMECTIN AND THE FORMULATION BASED ON IT MILBEKNOK 1%, CE

Relevance. The priorities of modern agricultural production are the application of new pesticides that are highly effective, safe for humans and do not have a negative impact on environmental objects. The most promising is the synthesis of substances from natural materials or their synthetic analogues (pesticides of biological origin). These include avermectin class substance – milbemectin.
 Objective of the work was the toxicological and hygienic evaluation of the new active ingredient of the aversectins class - milbemectin and the formulation based on it Milbeknok 1%, CE, substantiation of the acceptable daily dose (ADD) of milbemectin.
 Materials and methods. Expert-analytical, toxicological and hygienic methods, analysis of literature data were used during the research. The hygienic assessment of the toxicity of milbemectin and the formulation based on it was carried out in accordance with State Standard 8.8.1.002-98 “Hygienic classification of pesticides by degree of hazard”.
 Results. The analysis of the acute toxicity of the formulation and its active ingredient showed that Milbeknok 1%, CE, according to State Standard 8.8.1.002-98, belongs to the 3rd class of hazard, and milbemectin – to the 2nd class, according to the limiting criterion – acute inhalation toxicity.
 In short-term and long-term experiments with rats, mice and dogs, the main effect of milbemectin exposure was general toxicity and hepatotoxicity. According to carcinogenicity, reproductive and embryotoxicity, milbemectin is pertained to the 3rd class of hazard.
 Substantiating the ADD of milbemectin we used the smallest NO(A)EL value of 3 mg/kg, established for the general toxic effect in the experiment to study the chronic effect on dogs and safety factor of 1000 (taking into account the lack of a study of developmental neurotoxicity and limited data on reproductive toxicity of the compound): ADD = 3/1000 = 0.003 mg/kg.
 Conclusions. It was established that the Milbeknok 1%, CE pertains to the 3rd class, and its active substance - to the 2nd class of hazard, according to the limiting criterion – acute inhalation toxicity. The substantiated ADD value of milbemectin is 0.003 mg/kg.

The Acute and Short-Term Inhalation of Carbon Nanofiber in Sprague-Dawley Rats.

The inhalation toxicity of carbon nanofibers (CNFs) is not clearly known due to relatively few related studies reported. An acute inhalation study and short-term inhalation study (5 days) were therefore conducted using Sprague-Dawley rats. In the acute inhalation study, the rats were grouped and exposed to a fresh air control or to low (0.238 ± 0.197), moderate (1.935 ± 0.159), or high (24.696 ± 6.336 mg/m3) CNF concentrations for 6 h and thereafter sacrificed at 14 days. For the short-term inhalation study, the rats were grouped and exposed to a fresh air control or low (0.593 ± 0.019), moderate (2.487 ± 0.213), or high (10.345 ± 0.541 mg/m3) CNF concentrations for 6 h/day for 5 days and sacrificed at 1, 3, and 21 days post-exposure. No mortality was observed in the acute inhalation study. Thus, the CNF LC50 was higher than 25 mg/m3. No significant body or organ weight changes were noted during the 5 days short-term inhalation study or during the post-exposure period. No significant effects of toxicological importance were observed in the hematological, blood biochemical, and coagulation tests. In addition, the bronchoalveolar lavage (BAL) fluid cell differential counts and BAL inflammatory markers showed no CNF-exposure-relevant changes. The histopathological examination also found no CNF-exposure-relevant histopathological lesions. Thus, neither acute nor 5 days inhalation exposure to CNFs induced any noticeable toxicological responses.

Development of an Integrated Platform to Assess the Physicochemical and Toxicological Properties of Wood Combustion Particulate Matter.

Wood burning contributes to indoor and ambient particulate matter (PM) pollution and has been associated with increased morbidity and mortality. Here, we present an integrated methodology that allows to generate, sample, and characterize wood smoke derived from different moisture contents and representative combustion conditions using pine wood as a model. Flaming, smoldering, and incomplete combustion were assessed for low-moisture pine, whereas both low-moisture pine and high-moisture pine were investigated under flaming conditions. Real-time monitoring of carbon monoxide, volatile organic compounds, and aerosol number concentration/size in wood smoke was performed. The PM was size-fractionated, sampled, and characterized for elemental/organic carbon, organic functional groups, and inorganic elements. Bioactivity of PM was assessed by measuring the sterile alpha motif (SAM) pointed domain containing ETS (E-twenty-six) transcription factor (SPDEF) gene promoter activity in human embryonic kidney 293 (HEK-293T) cells, a biomarker for mucin gene expression. Findings showed that moisture content and combustion condition significantly affected the organic and inorganic elemental composition of PM0.1 as well as its bioactivity. Also, for a given moisture and combustion scenario, PM chemistry and bioactivity differed considerably with PM size. Importantly, PM0.1 from flaming combustion of low-moisture pine contained the highest abundance of the oxygenated saturated aliphatic functional group [H-C-O] and was also biologically most potent in stimulating SPDEF promoter activity, suggesting the role of organic compounds such as carbohydrates and sugar alcohols (that contain [H-C-O]) in driving mucus-related respiratory outcomes. Our platform enables further well-controlled parametric studies using a combination of in vitro and in vivo approaches to link wood burning parameters with acute and chronic inhalation health effects of wood smoke.

Assessment of Threshold Dose of Thoron Inhalation and Its Biological Effects by Mimicking the Radiation Doses in Monazite Placer Deposits Corresponding to the Normal, Medium and Very High Natural Background Radiation Areas.

The dose contributed from thoron (220Rn) and its progeny has been neglected in the dose assessment because of its short half-life (t1/2 = 55.6s) and generally low concentrations. Recently, concentrations of 220Rn gas and its progeny were found to be pronounced in the traditional residential dwellings in China, on beaches of India and in other countries. Accordingly, we investigated the biological effects of thoron (220Rn) decay products in various mouse organs, succeeding inhalation of thoron gas in BALB/c mouse. We investigated the biological effects upon thoron inhalation on mouse organs with a focus on oxidative stress. These mice were divided into (4 random groups): sham inhalation, thoron inhalation for 1, 4 and 10days. Various tissues (lung, liver and kidney) were then collected after the time points and subjected to various biochemical analyses. Immediately after inhalation, mouse tissues were excised for gamma spectrometry and 72h post inhalation for biochemical assays. The gamma spectrometry counts and its subsequent calculation of the equivalent dose showed varied distribution in the lung, liver and kidney. Our results suggest that acute thoron inhalation showed a differential effect on the antioxidant function and exerted pathophysiological alterations via oxidative stress in organs at a higher dose. These findings suggested that thoron inhalation could alter the redox state in organs; however, its characteristics were dependent on the total redox system of the organs as well as the thoron concentration and inhalation time.

P13-19 Enhanced study design for acute inhalation studies with hydrophobic surface treated particles to reveal the issue of suffocation through strong agglomeration of particles in the nose of test animals

P13-19 Enhanced study design for acute inhalation studies with hydrophobic surface treated particles to reveal the issue of suffocation through strong agglomeration of particles in the nose of test animals

Toxicological Evaluation of Silver Nanoparticles Synthesized with Peel Extract of Stenocereus queretaroensis.

Silver nanoparticles (AgNPs) synthesized with plants are widely used in different industries, such as the medical, industrial, and food industries; however, their hazards and risks remain unclear. Here, we aimed to evaluate the toxicological effects of AgNPs in both in vitro and in vivo models. Previously, we developed and characterized green synthesized AgNPs based on Stenocereus queretaroensis (S. queretaroensis). The present study evaluates the toxicity of these AgNPs through cytotoxicity and mutagenicity tests in vitro, as well as genotoxicity tests, including the evaluation of acute oral, dermal, and inhalation toxicity, along with dermal and ocular irritation, in vivo, according to guidelines of The Organization for Economic Co-operation and Development (OECD). We evaluated cell cytotoxicity in L929 cells, and the half-maximal inhibitory concentration was 134.76 µg/mL. AgNPs did not cause genotoxic or mutagenic effects. Furthermore, in vivo oral, dermal, and acute inhalation toxicity results did not show any adverse effects or mortality in the test animals, and after the dermal and ocular irritation assessments, the in vivo models did not exhibit irritation or corrosion. Therefore, the results show that these previously synthesized S. queretaroensis AgNPs do not represent a risk at the tested concentrations; however, little is known about the effects that AgNPs induce on physiological systems or the possible risk following long-term exposure.

Acute, repeated inhalation toxicity, respiratory system irritation, and mutagenicity studies of 1,1,2,2-tetrafluoroethane (HFC-134) as the impurity in the pharmaceutical propellant 1,1,1,2-tetrafluoroethane (HFA-134a)

HFC-134 is the main impurity of HFA-134a. In order to verify the rationality of HFC-134 limits in HFA-134a and ensure the safety of HFA-134a as propellant in pharmaceutical metered-dose inhalers, acute inhalation toxicity, seven-day repeat dose inhalation irritation study, 21-day repeat dose inhalation toxicity study and reverse mutation assay of HFC-134 were tested to evaluate its inhalation safety. In acute inhalation studies, Sprague-Dawley rats were exposed nose-only to HFC-134 at levels of 100 000, 200 000, 400 000, 600 000, and 800 000 ppm for 4 h. Based on the mortality incidence, the calculated four-hour LC50 value for HFC-134 is 532 069 ppm for males and 502 058 ppm for females and acute inhalation toxicity is manifested as the lung lobes turn dark red. Exposures to 836 ± 67 ppm for 4 hours/day 7 days/week continuously did not induce local irritation of the respiratory system in Sprague-Dawley rats. Sprague-Dawley rats were exposed nose-only to HFC-134 at levels of 0 (control), 203 929 ppm and 394 871 ppm 2 h/day for 21 consecutive days, no significant treatment-related adverse effects was noted. Results from Ames studies demonstrated that HFC-134 was not mutagenic. Although HFC-134 has a very low acute inhalation toxicity, considering that its acute inhalation toxicity is higher than that of HFA-134a, and due to the high frequency of use of MDI by asthma patients, acceptance criteria of HFC-134 as the impurity in aerosol propellant HFA-134a should be lower than 8-h TWA WEEL value of 1000 ppm to ensure the safety of the MDI.

Experimental study of toxic properties of a lead-tin-selenium-tellurium solid solution

Introduction. Solid solutions are widely used in the manufacture of particularly sensitive and high-precision devices, various kinds of sensors and energy converters, which causes a large number of workers to come into contact with them. The purpose of the study: to conduct experimental research and estimate biological effect of a solid lead-tin-selenium-tellurium (LTST) solution on warm-blooded animals. Materials and methods. Solid solution (lead (52%), tin (8%), selenium (trace) and tellurium (40%) - powder insoluble in water. Experiments were carried out on mice, rats and rabbits. Acute and chronic toxicity, cumulative properties, fibrogenic activity, irritant effect on skin and mucous membranes were evaluated. Results. According to the parameters of acute toxicity LTST is a low-hazard compound (Hazard Class 4), it has an irritant effect on skin and mucous membranes, the expressed cumulative properties (Kcum - 2.58). General toxic effect of the alloy is characterized by changes in functional state of kidneys, hematopoietic function, blood coagulation system. The compound has a moderately pronounced fibrogenic effect. Limitations. The limitation of this study is the lack of literature data of toxicological studies on the biological effect of a solid solution of LTST was the basis for its study. Conclusions. The biological effect of a solid solution of LTST on the organism was studied for the first time on models of acute, subacute and chronic experiments. According to GOST 12.1.077-76 LTST belongs to Hazard Class 4 (low-hazardous compound).The solid solution has been established to belong to compounds which may cause acute inhalation poisoning (Limac - 46.73 mg/m3). LTST is dangerous in terms of the development of chronic intoxication, has pronounced cumulative properties (Kcum - 2.58). LTST has a general toxic effect, leads to disruption of hematopoietic function, increased content of coproporferin in urine, which is associated to a large extent with the presence of lead molecule in the solution. The solid solution causes the development of a fibrotic process of pulmonary tissue. LTST is less toxic than the lead in its composition. Control over the concentration of LTST in the air of the working area should be carried out according to the MPC = 0.05 mg/m3 (lead and its inorganic compounds).

Toxic and hygienic evaluation of the pyridine derivative — 2-ethyl-4-nitropyridine N-oxide

Introduction. The toxic and hygienic assessment of both the final product and intermediate synthesis products remains the key preventive measure to avoid intoxication of workers’ body by industrial xenobiotics in the chemical and pharmaceutical industry and in the context of a constant increase in the range of used compounds. In recent years, nitrogen-containing heterocyclic compounds of the pyridine group have been widely used in various industries. One of these substances is the anti-tuberculosis drug ethionamide, the intermediate product in the synthesis of which is 2-ethyl-4-nitropyridine N-oxide. Materials and methods. In experiments, the toxic properties of 2-ethyl-4-nitropyridine N-oxide were studied. The investigations were carried out on outbred rats and mice, rabbits and guinea pigs. The effect of the substance on experimental animals was assessed using standard physiological, biochemical, hematological and morphological indices. Intermediate toxicity was studied with different methods of substance administration (oral, percutaneous and inhalation) both in single and repeated experiments. The obtained results were processed using the Statistic 10.0 software package. Results. Mean lethal doses of 2-ethyl-4-nitropyridine N-oxide for female rats and male mice were 1250 mg/kg (976.6÷1600.0 mg/kg) and 430 mg/kg (355.4÷520.3mg/kg), respectively; for female mice - 675 mg/kg. The ability of the substance to accumulate was average: the cumulation coefficient was 4.0. There were no significant differences in the effect of the substance on animals of different species and gender. The substance didn’t show a local irritating effect on the skin, skin-resorptive and allergic effects, but a pronounced irritating effect on the mucous membranes of the eyes was revealed. In the subacute experiment, 2-ethyl-4-nitropyridine N-oxide showed a toxic effect mainly on the blood system. A specific damaging effect was revealed, which was expressed in an imbalance of the content of oxyhemoglobin and methemoglobin with a significant increase in the latter. The threshold index of acute inhalation effect was 76.7 mg/m3. The tentative safe exposure level in the air of the working area for the substance was calculated at the level of 0.5 mg/m3. Limitations. The investigation is limited to the study of the toxicological characteristics of 2-ethyl-4-nitropyridine N-oxide. In accordance with the directive documents on the protection of experimental animals, the limited number of in vivo experiments is connected with the dangers for animals and with public ethical views on in vivo experiments. Conclusion. The proposed tentative safe level of exposure to 2-ethyl-4-nitropyridine N-oxide in the air of the working area at the level of 0.5 mg/m3 makes it possible to attribute the xenobiotic to hazard class II. Under the conditions of compliance with the specified standard, the dose absorbed by the worker under the production conditions will be no more than 5-10 mg per work shift, which guarantees safety for health and minimizes the risk to the health of workers. Information on the toxicity of 2-ethyl-4-nitropyridine N-oxide can be useful for solving a wide range of tasks fixed in the control and supervisory activities of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing, hygienic rationing and monitoring, and will contribute to the prevention and reduction of incidence rate associated with the exposure to harmful factors of the production environment.

Chronic obstructive lung disease after ammonia inhalation burns: a report of two cases

Anhydrous ammonia is a commonly used chemical in industry. Ammonia gas inhalation causes thermal injuries and alkali burns in the airway and lung parenchyma. Previous case reports have stated that respiratory sequelae after acute ammonia inhalation burns were associated with structural lung disease, such as bronchiectasis or interstitial lung disease. We herein report two cases of long-term sequelae with persistent airflow limitation after ammonia inhalation burns.

Acute Effect of Bronchodilator on Intrathoracic Airway Wall Compliance in COPD Patients

PurposeIn patients with chronic obstructive pulmonary disease (COPD), bronchial responsiveness after acute administration of short acting bronchodilators is conventionally assessed by measuring the improvement of forced expiratory volume in the first second (FEV1) during a maximal forced expiratory maneuver. This study aimed to measure the variation of intrathoracic airway wall compliance (AWC) after acute administration of short acting beta-2 agonist in COPD patients since this might influence the final modification of airway caliber during maximal expiratory effort and the resulting bronchodilation as inferred by FEV1 changes.MethodsIn a group of 10 patients suffering from COPD, intrathoracic AWC was measured at middle (50% of Forced Vital Capacity (FVC) and low (75% of FVC) lung volumes using the interrupter method during forced expiratory maneuver in basal conditions and after acute inhalation of albuterol (salbutamol) (400 mcg by MDI). Ten healthy subjects were examined similarly as a control group.ResultsLower values of baseline intrathoracic AWC at both lung volumes were found in COPD patients (1.72 ± 0.20 ml/cmH2O and 1.08 ± 0.20 ml/cmH2O, respectively) as compared to controls (2.28 ± 0.27 ml/cmH2O and 1.44 ± 0.22 ml/cmH2O, respectively) (p < 0.001). In COPD patients, AWC increased significantly at both lung volumes after salbutamol, amounting to 1.81 ± 0.38 ml/cmH2O and 1.31 ± 0.39 ml/cmH2O, respectively (p < 0.01), but the relative change was not different from that observed in controls.ConclusionIn COPD patients, AWC is reduced compared to controls, but after bronchodilator, the intrathoracic airways become more compliant. The consequent increased collapsibility under high positive pleural pressure could limit the airway caliber improvement seen after bronchodilator, as assessed by the FEV1 changes during the forced expiratory maneuver, underestimating the effective bronchodilation achieved in these patients.

Biological effects of inhaled crude oil vapor. II. Pulmonary effects

Workers involved in oil exploration and production in the upstream petroleum industry are exposed to crude oil vapor (COV). COV levels in the proximity of workers during production tank gauging and opening of thief hatches can exceed regulatory standards, and several deaths have occurred after opening thief hatches. There is a paucity of information regarding the effects of COV inhalation in the lung. To address these knowledge gaps, the present hazard identification study was undertaken to investigate the effects of an acute, single inhalation exposure (6 h) or a 28 d sub-chronic exposure (6 h/d × 4 d/wk × 4 wks) to COV (300 ppm; Macondo well surrogate oil) on ventilatory and non-ventilatory functions of the lung in a rat model 1 and 28 d after acute exposure, and 1, 28 and 90 d following sub-chronic exposure. Basal airway resistance was increased 90 d post-sub-chronic exposure, but reactivity to methacholine (MCh) was unaffected. In the isolated, perfused trachea preparation the inhibitory effect of the airway epithelium on reactivity to MCh was increased at 90 d post-exposure. Efferent cholinergic nerve activity regulating airway smooth muscle was unaffected by COV exposure. Acute exposure did not affect basal airway epithelial ion transport, but 28 d after sub-chronic exposure alterations in active (Na+ and Cl¯) and passive ion transport occurred. COV treatment did not affect lung vascular permeability. The findings indicate that acute and sub-chronic COV inhalation does not appreciably affect ventilatory properties of the rat, but transient changes in airway epithelium occur.

Arc decomposition behavior of C 4 F 7 N/Air gas mixture and biosafety evaluation of its by‐products

At present, reports on the arc interruption and decomposition behaviour of a C4F7N/air gas mixture especially the biosafety of its by-products are limited. Herein, a 57% C4F7N/43% air gas mixture was employed as an arc-quenching medium to conduct 200 breaking tests on a load switch (630 A/24 kV). The arc interruption and decomposition behaviour of the gas mixture were evaluated, and the biosafety of the decomposition products was assessed based on an acute inhalation toxicity test. It was found that the average arcing time of the 200 breakings was about 10.1 ms and that breakings were basically completed at the zero-crossing of the second or third current half-cycle. The gas mixture after breaking decomposed dramatically (the C4F7N content decreased by 75.6%), generating a large number of gaseous by-products (CO, CF4, C2F6, C3F8, CF3CN, C4F8, CO2, C4F10N2, C3F6, C2N2, etc.) as well as solid by-products (carbon particles). The lethal concentration (LC50) of 50% (LC50, 4 h) of C4F7N/air after 200 breakings was 31 ppm (male mice) and 34 ppm (female mice), respectively, and the toxicity was classified as Grade 1. In general, C4F7N has an arc interruption capability, albeit weaker than that of SF6 under the same conditions. After breaking, the C4F7N gas mixture has a relatively high acute inhalation toxicity, and relevant safety protection measures for research or operation personnel are strictly needed.

Experimental substantiation of the tentatively safe level of diethyl disulfide in the air of the working area and the atmospheric air of populated areas

Introduction. Diethyl disulfide belongs to the group of dialkyl disulfides, is a part of disulfide oil and a mixture of dialkyl disulfides. As a result of industrial purification of hydrocarbon raw materials from mercaptans, tens of thousands of tons of dialkyldisulfides and their mixtures are accumulated annually, the toxicity and danger of which have not been fully studied. No hygiene standards have been developed for diethyl disulfide. Materials and methods. Studies of the effects of diethyl disulfide were carried out in non-linear animals (rats and mice). The toxic properties of diethyl disulfide were studied under the conditions of single and repeated exposure to the intragastric, intraperitoneal, inhalation and cutaneous routes of entry into the body. Results. Based on the studies carried out, the toxicometric parameters of diethyl disulfide were established. Average lethal dose with intragastric administration LD50 = 1575 mg/kg, average lethal concentration CL50 = 18700 mg/m3, coefficient of possible inhalation poisoning CPIP = 1.3, limit of acute inhalation action (Limac) is set at 120 mg/m3, acute zone Zac = 156, cumulation coefficient was 3.2. Diethyl disulfide does not have a skin-resorptive toxic effect, but it has a moderately pronounced irritating effect on the mucous membrane of the eyes. Limitations of the study. The results of the diethyl disulfide exposure assessment are given for two animal species and four main routes of entry. Conclusion. The data obtained indicate that diethyl disulfide is a moderately hazardous substance with a single intragastric, inhalation and cutaneous route of entry into the body. The cumulative properties of diethyl disulfide are moderately expressed. Based on the analysis of literature data, the results of experimental studies and mathematical forecasting, a value of 4.0 mg/m3 is recommended as an approximate safe level of exposure in the air of the working area, in the atmospheric air of urban and rural settlements - 0.04 mg/m3.

Inhalation of Silver Silicate Nanoparticles Leads to Transient and Differential Microglial Activation in the Rodent Olfactory Bulb.

Engineered silver nanoparticles (AgNPs), including silver silicate nanoparticles (Ag-SiO2 NPs), are used in a wide variety of medical and consumer applications. Inhaled AgNPs have been found to translocate to the olfactory bulb (OB) after inhalation and intranasal instillation. However, the biological effects of Ag-SiO2 NPs and their potential nose-to-brain transport have not been evaluated. The present study assessed whether inhaled Ag-SiO2 NPs can elicit microglial activation in the OB. Adult Sprague-Dawley rats inhaled aerosolized Ag-SiO2 NPs at a concentration of 1 mg/ml for 6 hours. On day 0, 1, 7, and 21 post-exposure, rats were necropsied and OB were harvested. Immunohistochemistry on OB tissues were performed with anti-ionized calcium-binding adapter molecule 1 and heme oxygenase-1 as markers of microglial activation and oxidative stress, respectively. Aerosol characterization indicated Ag-SiO2 NPs were sufficiently aerosolized with moderate agglomeration and high-efficiency deposition in the nasal cavity and olfactory epithelium. Findings suggested that acute inhalation of Ag-SiO2 NPs elicited transient and differential microglial activation in the OB without significant microglial recruitment or oxidative stress. The delayed and differential pattern of microglial activation in the OB implied that inhaled Ag-SiO2 may have translocated to the central nervous system via intra-neuronal pathways.

Experimental Study on the Transport and Alteration Behavior of Aerosols From Low Density Powders for Acute Inhalation Toxicology Studies.

Low density powders have a bulk density of less than 100 kg/m3 and are produced technically by flame pyrolysis of silicon tetrachloride (pyrogenic powders such as pyrogenic silica) or wet-chemically by sol-gel processes (e.g. silica-gel) or precipitation reactions using sodium silicate solution and a mineral acid. The transport and alteration behavior of aerosols from low density powders was investigated in a device for toxicological inhalation studies. The test conditions corresponded to those for acute toxicology studies according to OECD Guideline 436. The use of cascade impactors, required by guideline, has not proven successful for low density powders as the fragile agglomerate structures are destroyed during the measurement. As an alternative and non-invasive measurement method, laser diffraction spectroscopy has proved very successful in the present investigations. In particular, aerosols from pyrogenic powders of low density showed a distinctive tendency to re-agglomerate, especially at concentrations >500 mg/m3mm3. Investigation results indicate that aerosol particle size must be monitored over the entire acute inhalation test period for acute inhalation studies to be performed reliably.

No inflammatory effects after acute inhalation of barium sulfate particles in human volunteers

BackgroundMost threshold limit values are based on animal experiments. Often, the question remains whether these data reflect the situation in humans. As part of a series of investigations in our exposure lab, this study investigates whether the results on the inflammatory effects of particles that have been demonstrated in animal models can be confirmed in acute inhalation studies in humans. Such studies have not been conducted so far for barium sulfate particles (BaSO4), a substance with very low solubility and without known substance-specific toxicity. Previous inhalation studies with zinc oxide (ZnO), which has a substance-specific toxicity, have shown local and systemic inflammatory respones. The design of these human ZnO inhalation studies was adopted for BaSO4 to compare the effects of particles with known inflammatory activity and supposedly inert particles. For further comparison, in vitro investigations on inflammatory processes were carried out.MethodsSixteen healthy volunteers were exposed to filtered air and BaSO4 particles (4.0 mg/m3) for two hours including one hour of ergometric cycling at moderate workload. Effect parameters were clinical signs, body temperature, and inflammatory markers in blood and induced sputum. In addition, particle-induced in vitro-chemotaxis of BaSO4 was investigated with regard to mode of action and differences between in vivo and in vitro effects.ResultsNo local or systemic clinical signs were observed after acute BaSO4 inhalation and, in contrast to our previous human exposure studies with ZnO, no elevated values of biomarkers of inflammation were measured after the challenge. The in vitro chemotaxis induced by BaSO4 particles was minimal and 15-fold lower compared to ZnO.ConclusionThe results of this study indicate that BaSO4 as a representative of granular biopersistent particles without specific toxicity does not induce inflammatory effects in humans after acute inhalation. Moreover, the in vitro data fit in with these in vivo results. Despite the careful and complex investigations, limitations must be admitted because the number of local effect parameters were limited and chronic toxicity could not be studied.